Papers - HAGIYA Hideharu

Iatrogenic fever of unknown origin. International journal

Shinnosuke Fukushima, Hideharu Hagiya, Keiji Yunoki, Gentaro Kato, Shinichi Mukai

Internal and emergency medicine   2025.3

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DOI： 10.1007/s11739-025-03915-5

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Genetic variability in Neisseria meningitidis strains isolated in a Japanese hospital

Kazuyoshi Gotoh, Shinnosuke Fukushima, Hideharu Hagiya, Shuma Tsuji, Koji Iio, Osamu Matsushita

IJID Regions   14   100511 - 100511   2025.3

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ijregi.2024.100511

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Intention and potential determinants of COVID-19 vaccination among healthcare workers at a single university hospital in Japan, 2024–2025 pre-season

Hideharu Hagiya, Yasushi Fujita, Takashi Kiguchi, Yohei Manabe

Journal of Infection and Chemotherapy   31 ( 3 )   102660 - 102660   2025.3

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.jiac.2025.102660

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A fatal case of enterovirus A71-induced meningoencephalitis following allogenic hematopoietic stem cell transplantation. International journal

Yayoi Ueda, Hiroki Kobayashi, Hideaki Fujiwara, Hideharu Hagiya, Risa Hashida, Saya Kubota, Mami Takemoto, Kenta Hayashino, Kanako Fujiwara, Tomohiro Nagano, Ryuichiro Hiyama, Keiko Fujii, Takumi Kondo, Keisuke Seike, Noboru Asada, Daisuke Ennishi, Nobuharu Fujii, Ken-Ichi Matsuoka, Maeda Yoshinobu

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   31 ( 4 )   102630 - 102630   2025.1

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Enterovirus A71 (EV-A71) is a major pathogen responsible for hand, foot, and mouth disease (HFMD) in infants and children. EV-A71 infection represents an epidemic in the Asia-Pacific region, and can cause serious central nervous system (CNS) infections in immunocompromised patients that can result in paralysis, disability, or death. There have been few reports in the literature concerning EV-A71 CNS infections after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adult patients. We describe the case of a 63-year-old woman with EV-A71 meningoencephalitis who underwent a second allo-HSCT for relapsed refractory myelodysplastic syndrome. She developed disturbance of consciousness during intubation due to severe pulmonary impairment following allo-HSCT. Despite the absence of pleocytosis in the cerebrospinal fluid, enterovirus was detected in her cerebral spinal fluid using the Biofire® FilmArray® Meningitis/Encephalitis (ME) panel, which was later identified as EV-A71 at a referral center. Despite a transient improvement in her level of consciousness after intravenous immunoglobulin administration, she did not fully recover. The patient also showed muscle weakness as well as pulmonary impairment that necessitated a tracheotomy. Our case demonstrated the utility of the FilmArray® ME panel as a screening tool for detecting multiple potential pathogens until a specific pathogen could be identified using other diagnostic methods. Clinicians should be aware that EV-A71 CNS infection can occur among adults with severe immunodeficient conditions, and that it leads poor clinical outcomes. Our case suggests that continuous monitoring for this potentially fatal pathogen is warranted for immunocompromised patients.

DOI： 10.1016/j.jiac.2025.102630

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Odontogenic cervical intramedullary abscesses. International journal

Shinnosuke Fukushima, Hideharu Hagiya

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia   133   111026 - 111026   2024.12

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DOI： 10.1016/j.jocn.2024.111026

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International trends in biliary tract cancer-related mortality, 2000-2022: An observational study of the World Health Organization mortality database. International journal

Quynh Thi Vu, Yoshito Nishimura, Ko Harada, Hiroki Ito, Tsukasa Higashionna, Akinari Maruo, Keisaku Harada, Tatsuaki Takeda, Hirofumi Hamano, Yoshito Zamami, Hideharu Hagiya, Toshihiro Koyama

Hepatology (Baltimore, Md.)   2024.12

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BACKGROUND AIMS: Biliary tract cancers (BTCs), including intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), gallbladder cancer (GBC), and ampullary cancer, exhibit poor prognosis. This study examined temporal trends in mortality due to BTCs and their major subtypes at international, regional, and national levels. APPROACH RESULTS: This observational study used the World Health Organization mortality database. Locally weighted regression (LOESS) was used to produce a smoothed curve of long-term international and regional BTC and major subtype-related mortality rates in 2000-2022 based on available data from countries. Trends in age-standardised mortality rates (ASRs) during 2013-2022 for individual countries were examined using joinpoint regression analysis. Internationally, LOESS-smoothed ASRs per 100,000 population due to BTCs were 2.8 (95% confidence interval: 2.5-3.1) in 2000, and 2.7 (2.3-3.1) in 2022. LOESS-smoothed BTC-related ASRs were the highest in the Western Pacific region at 4.2 (1.8-6.6) in 2022, compared with those in the European and American regions at 2.6 (2.3-2.9) and 2.2 (1.8-2.6), respectively. Among major subtypes, LOESS-smoothed ASRs due to iCCA increased by 120.0%, those due to GBC decreased by 45.5%, and those due to eCCA remained stable between 2000 and 2022. Disparities in BTC and major subtype-related ASR trends were observed between countries during 2013-2022, with iCCA-associated ASRs showing increasing trends in many countries. CONCLUSIONS: Although internationally estimated BTC-associated ASRs showed a stable trend over the last two decades, a large increase in estimated iCCA-associated ASRs necessitates developing effective screening for high-risk individuals and disease management strategies.

DOI： 10.1097/HEP.0000000000001200

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Trends in the growing impact of group A Streptococcus infection on public health after COVID-19 pandemic: a multicentral observational study in Okayama, Japan. International journal

Shinnosuke Fukushima, Takashi Saito, Yoshitaka Iwamoto, Yuko Takehara, Haruto Yamada, Koji Fujita, Masayo Yoshida, Yasuhiro Nakano, Hideharu Hagiya

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology   2024.12

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PURPOSE: Following the COVID-19 pandemic, group A Streptococcus (GAS) infection has been surging worldwide. We aimed to compare the disease burden between notified cases of streptococcal toxic shock syndrome (STSS) and unreported GAS infections. METHODS: This is a multicentral observational study, retrospectively performed at seven hospitals in Okayama prefecture in Japan from January 2022, to June 2024. Clinical and microbiological data of patients with positive cultures of GAS were collected from the medical records. Primary outcomes were defined as rates of surgical procedures, intensive care unit (ICU) admission, and in-hospital mortality, which were compared among patients with locally-defined STSS, invasive GAS (iGAS), and non-iGAS infection. RESULTS: GAS was detected in 181 patients, with 154 active cases of GAS infection. The number of patients with GAS infection surged in late 2023. The most common source of infection was skin and soft tissue infections, accounting for 83 cases, including 15 cases of necrotizing fasciitis, and 12 cases (7.8%) were notified to public health authorities as STSS. Among the 25 unreported iGAS cases, 9 (36.0%) underwent surgical intervention, and 4 patients (16.0%) required ICU admission. The mortality rates in the unreported iGAS cases were comparable to those observed in the notified STSS. CONCLUSIONS: We highlighted that the number of iGAS infections was twofold higher than that of notified STSS, with comparable mortality rate between these groups, indicating substantial underestimation of the true burden of iGAS. This epidemiological investigation has significant implications for enhancing infectious disease surveillance frameworks and public health policy development.

DOI： 10.1007/s10096-024-05015-2

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Clinical and microbiological characteristics of high-level daptomycin-resistant Corynebacterium species: A systematic scoping review. Reviewed International journal

Shinnosuke Fukushima, Hideharu Hagiya, Kazuyoshi Gotoh, Shuma Tsuji, Koji Iio, Hidemasa Akazawa, Osamu Matsushita, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   2024.12

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INTRODUCTION: Corynebacterium species potentially develop high-level daptomycin resistance (HLDR) shortly after daptomycin (DAP) administration. We aimed to investigate the clinical and microbiological characteristics of HLDR Corynebacterium infections. METHODS: We first presented a clinical case accompanied by the results of a comprehensive genetic analysis of the isolate, and then performed a systematic scoping review. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews, we searched for articles with related keywords, including "Corynebacterium", "Daptomycin", and "Resistance", in the MEDLINE and Web of Science databases from the database inception to October 25, 2024. Clinical case reports and research articles documenting the isolation of HLDR Corynebacterium species, defined by a minimum inhibitory concentration of DAP at ≥256 μg/mL, were deemed eligible for this review. RESULTS: Of 80 articles screened, seven case reports detailing eight cases of HLDR Corynebacterium infections, as well as five research articles, were included. C. striatum was the most common species (7/9 cases, 77.8%), and prosthetic device-associated infections accounted for 66.7% of the cases. Duration of DAP administration before the emergence of HLDR isolates ranged from 5 days to 3 months; three-quarters of the cases developed within 17 days. Three HLDR isolates were genetically confirmed to have an alteration in pgsA2. The majority of the patients were treated with either glycopeptides or linezolid, with favorable outcomes. In vitro experiments confirmed that C. striatum strains acquire the HLDR phenotype at higher rates (71% to 100%) within 24 hours of incubation, compared to other Corynebacterium strains CONCLUSION: DAP monotherapy, especially for prosthetic device-associated infections, can result in the development of HLDR Corynebacterium. Additional research is warranted to investigate the clinical implications of this potentially proliferating antimicrobial resistant pathogen.

DOI： 10.1016/j.jiac.2024.12.004

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Epidemiology and Clinical Features of Patients with Tick Bites in the Japanese Spotted Fever-Endemic Zone. Reviewed International journal

Shinnosuke Fukushima, Takaomi Sumida, Osamu Kawamata, Yoshimi Hidani, Hideharu Hagiya

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   2024.12

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PURPOSE: This study aimed to clarify the epidemiology and clinical features of tick bites in a Japanese spotted fever (JSF)-endemic area. METHOD: The clinical records of patients with tick bites were retrospectively reviewed based on a survey conducted at Numakuma Hospital, Fukuyama City, Hiroshima, Japan, from 2016-2023. Data on basic characteristics, visit dates, residential address, exposure activities, tick-bite sites, and prophylactic antimicrobial prescriptions for each patient with tick bites were collected at the JSF hotspot hospital. RESULTS: A total of 443 patients with tick bites visited the hospital, of which data on 305 cases (68.8%) were reviewed. The median age of these patients was 71 years, with a higher proportion of women (63.0%). One-third of the patients had a preceding history of working in fields, whereas two-thirds had entered mountains or agricultural fields. Nearly 90% of the patients visited the hospital from April to August, and the most common bite sites were the lower extremities (45.1%). Most patients (76.1%) resided in the southern area of Numakuma Hospital. Nearly all patients were prescribed prophylactic antibiotics (minocycline in 87.8% of cases), and none subsequently developed JSF. CONCLUSION: Continued surveillance of patients with tick bites is warranted to better understand changes in the clinical impact of tick-borne diseases.

DOI： 10.1016/j.jiac.2024.11.020

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Clinical characteristics of female long COVID patients with menstrual symptoms: a retrospective study from a Japanese outpatient clinic. Reviewed International journal

Yasue Sakurada, Yui Matsuda, Kanon Motohashi, Toru Hasegawa, Yuki Otsuka, Yasuhiro Nakano, Kazuki Tokumasu, Koichiro Yamamoto, Naruhiko Sunada, Hiroyuki Honda, Hideharu Hagiya, Keigo Ueda, Fumio Otsuka

Journal of psychosomatic obstetrics and gynaecology   45 ( 1 )   2305899 - 2305899   2024.12

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PURPOSE: To elucidate the impact of long COVID on menstruation and mental health, medical records of patients with long COVID were evaluated. METHODS: Symptoms of long COVID, QOL, mental health, and related endocrine data were compared between two groups with and without menstrual disturbances. RESULTS: Of 349 female patients who visited our clinic between February 2021 and March 2023, 223 patients with long COVID (aged 18-50 years) were included. Forty-four (19.7%) of the patients had menstrual symptoms associated with long COVID. The patients with menstrual symptoms were older than those without menstrual symptoms (42.5 vs. 38 years). The percentage of patients with menstrual symptoms was higher during the Omicron phase (24%) than during the Preceding (13%) and Delta (12%) phases. Cycle irregularity was the most frequent (in 63.6% of the patients), followed by severe pain (25%), heavy bleeding (20.5%), perimenopausal symptoms (18.2%), and premenstrual syndrome (15.9%). Fatigue and depression were the most frequent complications. Scores for fatigue and for QOL were significantly worse in long COVID patients with menstrual symptoms. Results of endocrine examinations showed significantly increased cortisol levels in patients with menstrual complaints. CONCLUSION: Long COVID has an impact on menstrual conditions and on QOL related to menstrual conditions.

DOI： 10.1080/0167482X.2024.2305899

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Detailed regimens for the prolonged β-lactam infusion therapy. Reviewed International journal

Hideharu Hagiya

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   30 ( 12 )   1324 - 1326   2024.12

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

A recent systematic review and meta-analysis of randomized controlled trials (RCTs) evaluated the efficacy and safety of prolonged versus intermittent β-lactam infusion in adult sepsis patients. The findings revealed a significant decrease in all-cause mortality and marked clinical success in the prolonged infusion group. Unfortunately, however, the manuscript lacked data and discussion for the specific regimens of prolonged β-lactam infusion defined in the included 15 RCT studies, which are herein additionally provided. Excluding one RCT, all protocols adopted a continuous infusion for the prolonged treatment. Except for three RCTs, dosages and timings of bolus injection were clearly defined. The total daily antibiotic dose for the continuous therapy was equivalent to those recommended for intermittent therapy. We believe this supplementary data aids clinicians in providing prolonged β-lactam infusions, contributing to enhanced treatment outcomes for patients suffering from severe sepsis or septic shock.

DOI： 10.1016/j.jiac.2024.07.003

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日本紅斑熱好発地域におけるヒト吸血をきたしたダニ種および保有病原体の検討

福島 伸乃介, 後藤 和義, 辻 秀真, 角南 博, 中野 靖浩, 中本 健太, 萩谷 英大

日本臨床微生物学会雑誌   35 ( Suppl.1 )   306 - 306   2024.12

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Language：Japanese   Publisher：(一社)日本臨床微生物学会  

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Human Papillomavirus vaccination awareness and uptake among healthcare students in Japan. Reviewed International journal

Madoka Shimbe, Yuki Otsuka, Hideharu Hagiya, Yoichi Yamada, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   2024.11

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BACKGROUND: The vaccination rate for HPV (Human Papillomavirus) has remained significantly low in Japan because of the administrative suspension of active recommendation. This study investigates the awareness and uptake of the HPV vaccine among healthcare students in Japan following the reinstatement of active recommendation for young women in April 2022. METHODS: A web-based survey was administered to 2567 healthcare students from Okayama and Shujitsu Universities in Japan in July 2023. The survey assessed participants' backgrounds, immunization status, awareness of vaccine recommendations, and knowledge of cervical cancer across various demographics, including sex, academic year, and department (Medicine, Health Science, Pharmaceutical, and Dentistry). RESULTS: The response rate was 36.3 % (933 students; 181 male, 739 female, and 13 unspecified gender). The overall immunization rate among female students was 55.6 %, with higher rates observed in medical (73.8 %) and dental (63.0 %) students. Awareness of the government's change in vaccine recommendation was notably high among female and senior male students. Over half of the female students (54.7 %) reported receiving vaccinations based on their parents' advice. Among those unvaccinated but interested in future immunization, concerns about adverse reactions (47.4 %) and challenges in scheduling vaccinations (29.1 %) were predominant. CONCLUSION: Healthcare students exhibited a higher HPV vaccination rate than the general population. Ongoing education to improve vaccine literacy is crucial for augmenting HPV vaccination rates in Japan.

DOI： 10.1016/j.jiac.2024.11.004

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Letter to the Editor: "Real-World Effectiveness of Ensitrelvir in Reducing Severe Outcomes in Outpatients at High Risk for COVID-19". Reviewed International journal

Hideharu Hagiya

Infectious diseases and therapy   13 ( 11 )   2461 - 2462   2024.11

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Authorship：Lead author,　Last author,　Corresponding author   Language：English  

DOI： 10.1007/s40121-024-01053-7

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Ethical consumption of antimicrobial agents: A proposal for a new concept in promoting antimicrobial stewardship. Reviewed International journal

Hideharu Hagiya

The American journal of the medical sciences   368 ( 5 )   553 - 555   2024.11

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Authorship：Lead author,　Last author,　Corresponding author   Language：English  

DOI： 10.1016/j.amjms.2024.07.002

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Addressing the Rejection of a Rebuttal Letter: Author's Experience and Thoughts. Reviewed

Hideharu Hagiya

JMA journal   7 ( 4 )   628 - 629   2024.10

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Authorship：Lead author,　Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.31662/jmaj.2024-0102

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Phenotypic and Genetic Characteristics of Carbapenemase-Producing Enterobacterales Isolates at Okayama University Hospital. Reviewed

Kazuyoshi Gotoh, Makoto Miyoshi, I Putu Bayu Mayura, Shuma Tsuji, Koji Iio, Shinnosuke Fukushima, Osamu Matsushita, Hideharu Hagiya

Acta medica Okayama   78 ( 5 )   371 - 376   2024.10

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Spread of carbapenemase-producing Enterobacterales (CPE) is an ongoing public health issue worldwide, including in Japan. In this study, we investigated the phenotypic and genetic characteristics of CPE isolates at Okayama University Hospital over the 5 years (2013-2018) prior to the outbreak of the 2019 coronavirus pandemic. Of 24 carbapenem-resistant Enterobacterales isolated during the study period, we identified 8 CPE isolates harboring blaIMP-1 (5 isolates) and blaIMP-6 genes (3 isolates). Bacterial species and carbapenem susceptibility patterns exhibited diversity. Minimum inhibitory concentrations (MICs) of meropenem were generally higher than those of imipenem and biapenem. Results of pulsed-field gel electrophoresis demonstrated that neither clonal nor plasmid-mediated outbreaks of blaIMP-harboring CPE isolates have developed at our hospital. One Klebsiella oxytoca isolate showed a high MIC (128 μg/mL) of meropenem, which could be explained by the high plasmid copy number. Subsequent analysis of this isolate may elucidate the intricacies of carbapenem resistance profiles among CPE isolates. Collectively, our findings underscore the necessity for ongoing genetic surveillance of CPE, complemented by tailored approaches for infection prevention and control.

DOI： 10.18926/AMO/67657

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Threat of MRSA bacteremia still matters: a propensity score matching analysis. Reviewed International journal

Shinnosuke Fukushima, Hideharu Hagiya, Naoki Kuninaga, Yuto Haruki, Haruto Yamada, Yoshitaka Iwamoto, Masayo Yoshida, Kota Sato, Yoshihisa Hanayama, Shuichi Tanaka, Tomoko Miyoshi, Yuki Otsuka, Keigo Ueda, Fumio Otsuka

Infection   2024.9

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DOI： 10.1007/s15010-024-02382-y

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Cefazolin inoculum effect in methicillin-susceptible Staphylococcus aureus clinical isolates Reviewed International journal

Shuma Tsuji, Kazuyoshi Gotoh, Tadahiro Manabe, Koji Iio, Shinnosuke Fukushima, Osamu Matsushita, Hideharu Hagiya

Diagnostic Microbiology and Infectious Disease   110 ( 1 )   116399 - 116399   2024.9

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We investigated the prevalence and characteristics of Cefazolin inoculum effect (CInE) among clinical MSSA isolates in Japan. Although 35.5 % (39 isolates) were positive for the blaZ gene, none met the phenotypic criteria for CInE. Our findings suggested a very low prevalence of CInE among MSSA isolates in our clinical setting.

DOI： 10.1016/j.diagmicrobio.2024.116399

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出血性脳梗塞,肺塞栓,深部静脈血栓症を合併したCOVID-19の1例

長谷川 功, 山本 紘一郎, 中本 健太, 平 佑貴, 庵谷 紘美, 中野 靖浩, 萩谷 英大, 大塚 文男

日本病院総合診療医学会雑誌   20 ( 5 )   289 - 294   2024.9

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Language：Japanese   Publisher：(一社)日本病院総合診療医学会  

52歳男性。COVID-19発症7日後に経皮的動脈血酸素飽和度94%(リザーバー10L/分投与下),右眼球共同偏倚と左半側空間無視,左上下肢完全麻痺をきたし搬送された。単純CTでは頭部で右中大脳動脈領域低吸収域を認め,胸部では両側広範囲の末梢優位のすりガラス影を認めた。造影CTでは右下肺動脈と左大腿静脈・膝窩静脈に血栓を認め,脳梗塞と肺塞栓症・深部静脈血栓症を合併した重症COVID-19と診断した。経過中に出血性脳梗塞を発症するも救命し得た。脳梗塞・肺塞栓を合併したCOVID-19では出血性脳梗塞の発症を念頭に慎重なフォローが必要である。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2024&ichushi_jid=J05937&link_issn=&doc_id=20241218260009&doc_link_id=10.60227%2Fjhgmwabun.20.5_289&url=https%3A%2F%2Fdoi.org%2F10.60227%2Fjhgmwabun.20.5_289&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Trends in the hand hygiene practices by alcohol-based hand rubs in Japanese hospitals before and after the novel coronavirus pandemic: an observational study using national surveillance data. Reviewed International journal

Tsukasa Higashionna, Hideharu Hagiya, Yasushi Fujita, Takashi Kiguchi

The Journal of hospital infection   2024.8

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BACKGROUND: Healthcare-associated infections (HAIs) are a global concern in healthcare facilities, for which hand hygiene (HH) using alcohol-based hand rubs (ABHR) is fundamentally crucial for their prevention. While previous studies report improvements in HH compliance amid the COVID-19 pandemic, the real situation in Japanese medical settings remains unclear. METHODS: This observational study sought data from the Japanese national surveillance, focusing on ABHR use in hospitals before and after the COVID-19 pandemic. Data were retrieved from facilities certified to receive the Additional Healthcare Reimbursements for Infection Prevention and Control I. The study spanned five years (2019-2023), segmented quarterly, and employed Joinpoint regression analysis to assess the annual percentage change (APC). RESULTS: Overall, ABHR use per patient per day significantly increased both in critical care units and general wards amid the pandemic. However, the APC in the critical care units demonstrated a downward trend from Q4 of 2021 to Q1 of 2023, and ABHR use in general wards remained below the amount of WHO recommendations. CONCLUSION: This trend analysis highlighted recent patterns of ABHR use in Japanese hospitals by comparing pre- and post-COVID-19 periods. Although increases in ABHR use were observed over time, sustained efforts to promote HH compliance are necessary, particularly in general wards.

DOI： 10.1016/j.jhin.2024.08.007

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Cryptococcal prostatitis in an immunocompromised patient with tocilizumab and glucocorticoid therapy: A case report. Reviewed International journal

Kohei Oguni, Shinnosuke Fukushima, Hideharu Hagiya, Atsushi Kato, Atsuhito Suyama, Takehiro Iwata, Yoshia Miyawaki, Sawako Ono, Koji Iio, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   2024.8

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Cryptococcus prostatitis is an uncommon manifestation of cryptococcal infection that occurs mostly in immunocompromised patients. Tocilizumab, an anti-interleukin-6 receptor monoclonal antibody, has been associated with an increased risk of cryptococcal infections. However, there have been no documented cases of cryptococcal prostatitis in patients receiving tocilizumab therapy. We report a case of cryptococcal prostatitis in a 72-year-old man treated with glucocorticoids and tocilizumab for giant cell arteritis and granulomatosis with polyangiitis. The patient presented dysuria and his serum level of prostate-specific antigen was elevated. Magnetic resonance imaging revealed a prostate mass, and a prostate biopsy was performed, leading to a pathologic diagnosis of cryptococcal prostatitis. Fungal cultures for blood and urine were negative, while the cryptococcal antigen for both serum and urine showed positive results. There were no particular findings in the pulmonary and central nervous systems. The patient was successfully treated with oral fluconazole (400 mg/day) and was discharged. Although cryptococcal prostatitis is a rare entity, clinicians should note that an immunosuppressed patient may develop such a difficult-to-diagnose disease.

DOI： 10.1016/j.jiac.2024.08.009

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Ghost in blood culture. Reviewed International journal

Shinnosuke Fukushima, Hideharu Hagiya, Mami Okura, Koji Iio

Internal and emergency medicine   2024.8

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DOI： 10.1007/s11739-024-03731-3

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Effectiveness of Sensing Gloves-Applied Virtual Reality Education System on Hand Hygiene Practice: A Randomised Controlled Trial. Reviewed International journal

Mahiro Izumi, Hideharu Hagiya, Yuki Otsuka, Yoshiaki Soejima, Shinnosuke Fukushima, Mitsunobu Shibata, Satoshi Hirota, Toshihiro Koyama, Fumio Otsuka, Akio Gofuku

American journal of infection control   2024.8

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INTRODUCTION: We developed a virtual reality (VR) education system and evaluated its clinical utility for promoting hand hygiene practices. METHODS: This prospective, two-week, randomised controlled study conducted at Okayama University Hospital, Japan, from November 2023 to January 2024, involved 22 participants (18 medical students and four residents). A fully immersive 360° VR system (VIVE Pro Eye) using a head-mounted display and sensing gloves was used to develop three healthcare tasks in a virtual patient room-Environmental Cleaning, Gauze Exchange, and Urine Collection. After monitoring all participants' baseline usage data of portable hand-rubbing alcohol in the first week, we randomly assigned them into 1:1 groups (VR training and video lecture groups). The primary outcome was differences in hand-rubbed alcohol use before and after intervention. RESULTS: Before the intervention, alcohol use did not significantly differ between both groups. After the intervention, a significant increase in alcohol use was observed in the VR training group (median: 8.2 g vs. 16.2 g; p=0.019) but not in the video lecture group. CONCLUSION: Our immersive 360° VR education system enhanced hand hygiene practices. Infection prevention and control practitioners and digital technology experts must collaborate to advance the development of superior educational devices and content.

DOI： 10.1016/j.ajic.2024.08.003

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Narrower-Spectrum Therapeutic Approaches Are Warranted for Aspiration Pneumonia. Reviewed International journal

Hideharu Hagiya, Shinnosuke Fukushima

Chest   166 ( 2 )   e71-e72   2024.8

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DOI： 10.1016/j.chest.2024.03.021

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Increased Oxidative Stress and Decreased Citrulline in Blood Associated with Severe Novel Coronavirus Pneumonia in Adult Patients. Reviewed International journal

Mitsuru Tsuge, Eiki Ichihara, Kou Hasegawa, Kenichiro Kudo, Yasushi Tanimoto, Kazuhiro Nouso, Naohiro Oda, Sho Mitsumune, Goro Kimura, Haruto Yamada, Ichiro Takata, Toshiharu Mitsuhashi, Akihiko Taniguchi, Kohei Tsukahara, Toshiyuki Aokage, Hideharu Hagiya, Shinichi Toyooka, Hirokazu Tsukahara, Yoshinobu Maeda

International journal of molecular sciences   25 ( 15 )   2024.7

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This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia.

DOI： 10.3390/ijms25158370

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New Delhi Metallo-Beta-Lactamase Inhibitors: A Systematic Scoping Review. Reviewed International journal

Lutfun Nahar, Hideharu Hagiya, Kazuyoshi Gotoh, Md Asaduzzaman, Fumio Otsuka

Journal of clinical medicine   13 ( 14 )   2024.7

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Background/Objectives: Among various carbapenemases, New Delhi metallo-beta-lactamases (NDMs) are recognized as the most powerful type capable of hydrolyzing all beta-lactam antibiotics, often conferring multi-drug resistance to the microorganism. The objective of this review is to synthesize current scientific data on NDM inhibitors to facilitate the development of future therapeutics for challenging-to-treat pathogens. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews, we conducted a MEDLINE search for articles with relevant keywords from the beginning of 2009 to December 2022. We employed various generic terms to encompass all the literature ever published on potential NDM inhibitors. Results: Out of the 1760 articles identified through the database search, 91 met the eligibility criteria and were included in our analysis. The fractional inhibitory concentration index was assessed using the checkerboard assay for 47 compounds in 37 articles, which included 8 compounds already approved by the Food and Drug Administration (FDA) of the United States. Time-killing curve assays (14 studies, 25%), kinetic assays (15 studies, 40.5%), molecular investigations (25 studies, 67.6%), in vivo studies (14 studies, 37.8%), and toxicity assays (13 studies, 35.1%) were also conducted to strengthen the laboratory-level evidence of the potential inhibitors. None of them appeared to have been applied to human infections. Conclusions: Ongoing research efforts have identified several potential NDM inhibitors; however, there are currently no clinically applicable drugs. To address this, we must foster interdisciplinary and multifaceted collaborations by broadening our own horizons.

DOI： 10.3390/jcm13144199

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Rapid diagnostic testing for GAS necrotizing fasciitis. Reviewed International journal

Shinnosuke Fukushima, Hideharu Hagiya, Mami Okura, Koji Iio

Internal and emergency medicine   19 ( 6 )   1773 - 1774   2024.7

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DOI： 10.1007/s11739-024-03643-2

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抗ブドウ球菌エンドライシンのリンカー領域が機能に与える影響(Functional impact by shorting a linker region of a staphylococcal endolysin)

宗友 荘介, 内山 淳平, 内山 伊代, Thamonwan Wanganuttara, 津久井 利広, 萩谷 英大, 山本 由弥子, 神田 秀幸, 松下 治

日本細菌学雑誌   79 ( 2 )   265 - 265   2024.7

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Mimicker of Gram-positive Staphylococci. Reviewed International journal

Shinnosuke Fukushima, Takumi Fujimori, Hideharu Hagiya

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases   146   107145 - 107145   2024.6

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DOI： 10.1016/j.ijid.2024.107145

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Disseminated septic arthritis caused by Ureaplasma urealyticum in an immunocompromised patient with hypogammaglobulinemia after rituximab therapy. Reviewed International journal

Kohei Oguni, Shinnosuke Fukushima, Yuki Otsuka, Yoshiaki Soejima, Marina Kawaguchi, Yosuke Sazumi, Takumi Fujimori, Koji Iio, Noriyuki Umakoshi, Kazuki Yamada, Hideharu Hagiya, Fumio Otsuka

Infection   52 ( 6 )   2495 - 2499   2024.6

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PURPOSE: Ureaplasma urealyticum is a rare pathogen associated with septic arthritis that predominantly affects patients with hypogammaglobulinemia. Bacterial identification of fastidious organisms is challenging because they are undetectable by routine culture testing. To the best of our knowledge, this is the first report of septic arthritis induced by U. urealyticum infection in Japan. CASE DESCRIPTION: We describe the case of a 23-year-old Japanese female with secondary hypogammaglobulinemia (serum immunoglobulin level < 500 mg/dL), identified 8 years after treatment with rituximab. The patient presented with persistent fever and polyarthritis that were unresponsive to ceftriaxone and prednisolone. Contrast-enhanced computed tomography and gallium-67 scintigraphy revealed effusion and inflammation in the left sternoclavicular, hip, wrist, knee, and ankle joints. Although Gram staining and bacterial culture of the drainage fluid from the left hip joint were negative, the condition exhibited characteristics of purulent bacterial infection. The patient underwent empirical treatment with doxycycline, and her symptoms promptly resolved. Subsequent 16S ribosomal RNA (rRNA) gene sequencing of the joint fluid confirmed the presence of U. urealyticum, leading to the diagnosis of septic arthritis. Combination therapy with doxycycline and azithromycin yielded a favorable recovery from the inflammatory status and severe arthritic pain. CONCLUSION: This case highlights U. urealyticum as a potential causative agent of disseminated septic arthritis, particularly in patients with hypogammaglobulinaemia. The 16S rRNA gene analysis proved beneficial for identifying pathogens in culture-negative specimens, such as synovial fluid, in suspected bacterial infections.

DOI： 10.1007/s15010-024-02301-1

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抗ブドウ球菌エンドライシンのリンカー領域が機能に与える影響

宗友 荘介, 内山 淳平, 内山 伊代, Thamonwan Wanganuttara, 津久井 利広, 萩谷 英大, 山本 由弥子, 神田 秀幸, 松下 治

日本細菌学雑誌   79 ( 2 )   119 - 119   2024.6

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Thoughts on and Proposal for the Education, Training, and Recruitment of Infectious Disease Specialists. Reviewed

Hideharu Hagiya

Acta medica Okayama   78 ( 3 )   205 - 213   2024.6

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The global pandemic of COVID-19 has underscored the significance of establishing and sustaining a practical and efficient infection control system for the benefit and welfare of society. Infectious disease (ID) specialists are expected to take on leadership roles in enhancing organizational infrastructures for infection prevention and control (IPC) at the hospital, community, and national levels. However, due to an absolute shortage and an uneven distribution, many core hospitals currently lack the ID specialists. Given the escalating global risk of emerging and re-emerging infectious diseases as well as antimicrobial resistance pathogens, the education and training of ID specialists constitutes an imperative concern. As demonstrated by historical changes in the healthcare reimbursement system, the establishment and enhancement of IPC measures is pivotal to ensuring medical safety. The existing structure of academic society-driven certification and training initiatives for ID specialists, contingent upon the discretionary decisions of individual physicians, possesses both quantitative and qualitative shortcomings. In this article, I first address the present situations and challenges related to ID specialists and then introduce my idea of securing ID specialists based on the new concepts and platforms; (i) ID Specialists as National Credentials, (ii) Establishment of the Department of Infectious Diseases in Medical and Graduate Schools, (iii) Endowed ID Educative Courses Funded by Local Government and Pharmaceutical Companies, and (iv) Recruitment of Young Physicians Engaged in Healthcare Services in Remote Areas. As clarified by the COVID-19 pandemic, ID specialists play a crucial role in safeguarding public health. Hopefully, this article will advance the discussion and organizational reform for the education and training of ID specialists.

DOI： 10.18926/AMO/67195

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Optimization of Blood Culture in "Hospital without Infection Control Team or Microbiology Laboratories" Reviewed

FUKUSHIMA Shinnosuke, HAGIYA Hideharu, TSUJI Kentaro, HIRAIWA Chihiro, OE Keishi, KITA Shinya, OTA Shigeru, TADA Ryuhei, MIYASAKA Ei, SUNAMI Hiroshi, OMOTE Shizuma, OTSUKA Fumio

Kansenshogaku Zasshi   98 ( 3 )   306 - 310   2024.5

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The effectiveness of interventions by senior resident physicians to optimize blood culture examinations has rarely been reported. We compared the results of blood culture examinations performed before and after an intervention, which consisted of 1) holding a study session on blood culture, 2) informing the monthly contamination rate, 3) feeding back the blood culture results to the doctor who ordered the test, and 4) distributing the institutional manual. After the intervention, the contamination rate decreased from 7.7% to 2.4%, and the proportion of coagulase-negative staphylococci isolated decreased from 34.6% to 15.9%. Additional laboratory testing and antibiotic administration were ordered in 4 patients (30.8%) with suspected contamination. To reduce blood culture contamination, a multifaceted educational approach is essential. Our report highlights the fact that educational activities by senior residents could play a considerable role in promoting the optimization of blood culture examinations.

DOI： 10.11150/kansenshogakuzasshi.e23034

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Adherence to and clinical utility of "quality indicators" for Staphylococcus aureus bacteremia: a retrospective, multicenter study. Reviewed International journal

Shinnosuke Fukushima, Hideharu Hagiya, Naoki Kuninaga, Yuto Haruki, Haruto Yamada, Yoshitaka Iwamoto, Masayo Yoshida, Kota Sato, Yoshihisa Hanayama, Shuichi Tanaka, Tomoko Miyoshi, Yuki Otsuka, Keigo Ueda, Fumio Otsuka

Infection   52 ( 4 )   1527 - 1538   2024.5

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BACKGROUND: We aimed to improve the prognosis, treatment, and management of Staphylococcus aureus bacteremia (SAB) by evaluating the association between adherence to quality indicators (QIs) and clinical outcomes in patients with their clinical outcomes. METHODS: We retrospectively collected clinical and microbiological data on hospitalized patients with SAB from 14 hospitals (three with >  600, two with 401-600, five with 201-400, and four with ≤ 200 beds) in Japan from January to December 2022. The SAB management quality was evaluated using the SAB-QI score (ranging from 0 to 13 points), which consists of 13 QIs (grouped into five categories) based on previous literature. RESULTS: Of the 4,448 positive blood culture episodes, 289 patients with SAB (6.5%) were enrolled. The SAB-QI scores ranged from 3 to 13, with a median score of 9 points. The SAB-QI score was highest in middle-sized hospitals with 401-600 beds. Adherence to each of the four QI categories (blood culture, echocardiography, source control, and antibiotic treatment) was significantly higher in survived cases than in fatal cases. Kaplan-Meier curves with log-rank tests demonstrated that higher adherence to SAB-QIs indicated a better prognosis. Logistic regression analysis revealed that age, methicillin resistance, multiple comorbidities (≥ 2), and low SAB-QI score were significantly associated with 30-day mortality in patients with SAB. CONCLUSIONS: Our study highlights that greater adherence to the SAB-QIs correlates with improved patient outcomes. Management of patients with SAB should follow these recommended indicators to maintain the quality of care, especially for patients with poor prognosticators.

DOI： 10.1007/s15010-024-02284-z

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Evidence Still Pending: Post-Exposure Prophylactic Measures Against Varicella Zoster Virus. Reviewed International journal

Hideharu Hagiya, Shinnosuke Fukushima

Journal of the Pediatric Infectious Diseases Society   13 ( 6 )   336 - 336   2024.5

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DOI： 10.1093/jpids/piae041

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後腹膜線維症49症例における臨床的特徴 甲状腺機能に着目して

花山 宜久, 安藤 美穂, 大國 皓平, 徳増 一樹, 長谷川 功, 萩谷 英大, 大塚 文男

日本内分泌学会雑誌   100 ( 1 )   314 - 314   2024.5

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後腹膜線維症49症例における臨床的特徴 甲状腺機能に着目して

花山 宜久, 安藤 美穂, 大國 皓平, 徳増 一樹, 長谷川 功, 萩谷 英大, 大塚 文男

日本内分泌学会雑誌   100 ( 1 )   314 - 314   2024.5

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黄色ブドウ球菌菌血症(SAB)に対する診療の質指標(Quality Indicator)に関する多施設研究

福島 伸乃介, 萩谷 英大, 大塚 勇輝, 山田 晴士, 岩本 佳隆, 佐藤 恒太, 大塚 文男

日本感染症学会総会・学術講演会・日本化学療法学会学術集会合同学会プログラム・抄録集   98回・72回   np210 - np210   2024.5

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Language：Japanese   Publisher：日本感染症学会・日本化学療法学会  

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日本における播種性クリプトコッカス症の疫学的特徴ならびに地域性・季節性およびトレンドの解析

赤澤 英将, 福島 伸乃介, 萩谷 英大, 大塚 文男

日本感染症学会総会・学術講演会・日本化学療法学会学術集会合同学会プログラム・抄録集   98回・72回   np193 - np193   2024.5

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抗MRSAエンドライシンの機能改良に関する検討

宗友 荘介, 津久井 利広, 内山 伊代, 萩谷 英大, 内山 淳平, 神田 秀幸, 松下 治

日本感染症学会総会・学術講演会・日本化学療法学会学術集会合同学会プログラム・抄録集   98回・72回   np260 - np260   2024.5

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緑膿菌角膜潰瘍に対する人工抗菌酵素の開発研究

内山 淳平, 内山 伊代, 萩谷 英大, 松下 治, 福田 憲, 石田 わか, 山城 健児, 高知 大学

日本感染症学会総会・学術講演会・日本化学療法学会学術集会合同学会プログラム・抄録集   98回・72回   np260 - np260   2024.5

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伝播性薬剤耐性HIVにより進行性多巣性白質脳症を発症した一例

川口 満理奈, 萩谷 英大, 大塚 勇輝, 福島 伸乃介, 大塚 文男

日本感染症学会総会・学術講演会・日本化学療法学会学術集会合同学会プログラム・抄録集   98回・72回   np333 - np333   2024.5

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Antibody titers and the risk of infection during the SARS-CoV-2 Omicron phase in Bizen City, Japan. Reviewed International journal

Tomoka Kadowaki, Ayako Sasaki, Naomi Matsumoto, Toshiharu Mitsuhashi, Hideharu Hagiya, Soshi Takao, Takashi Yorifuji

The Journal of infectious diseases   230 ( 3 )   662 - 669   2024.4

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BACKGROUND: Understanding the association between the immune response and the risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has implications for forthcoming prevention strategies. We evaluated the association between antibody titers and the risk of infection for the general population during the Omicron-dominant phase. METHODS: This was a prospective cohort study of residents or people affiliated with institutions in Bizen City, which included 1,899 participants. We measured the titers of antibodies against SARS-CoV-2 repeatedly every 2 months from June 2022 to March 2023. Infection status was obtained from self-reported questionnaires and the official registry. We estimated risk ratios (RRs) for infection within 2 months of the date of each antibody measurement with 95% confidence intervals (CIs) based on antibody titer categories and spline functions. RESULTS: Compared with the <2,500 arbitrary unit (AU)/mL category, the 2,500-5,000, 5,000-10,000, and ≥10,000 AU/mL categories had adjusted RRs (95% CI) of 0.81 (0.61-1.08), 0.51 (0.36-0.72), and 0.41 (0.31-0.54), respectively. The spline function showed a non-linear relationship between antibody titer and risk. CONCLUSIONS: Higher antibody titers were associated with a lower risk. We demonstrate the usefulness of measuring an antibody titers to determine the appropriate timing for future vaccination.

DOI： 10.1093/infdis/jiae207

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Prostate abscess caused by ESBL-producing E. coli successfully treated with fosfomycin monotherapy. Reviewed International journal

Shinnosuke Fukushima, Yuki Otsuka, Hideharu Hagiya, Naoto Nishikawa, Fumio Otsuka

International journal of antimicrobial agents   63 ( 6 )   107182 - 107182   2024.4

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DOI： 10.1016/j.ijantimicag.2024.107182

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Burden of depressive disorders in Vietnam from 1990 to 2019: A secondary analysis of the Global Burden of Disease Study 2019. Reviewed International journal

Quynh Thi Vu, Ko Harada, Yoshito Nishimura, Hideharu Hagiya, Elizabeth Tan, Odifentse Mapula E Lehasa, Yoshito Zamami, Toshihiro Koyama

Journal of psychiatric research   172   420 - 426   2024.4

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Depressive disorders are among the leading causes of disability globally. However, information on the burden of depressive disorders in Vietnam is limited. We aimed to analyse the burden of depressive disorders in Vietnam from 1990 to 2019. Using data from the Global Burden of Disease Study 2019, prevalence and disability-adjusted life-years (DALYs) were used as indicators to analyse the burden of depressive disorders by age and sex. In 2019 in Vietnam, depressive disorders comprised 2629.1 thousand (95% uncertainty interval (UI): 2233.3-3155.9) estimated cases and 380.6 thousand (95% UI: 258.9-533.8) estimated DALYs. The crude prevalence rate of depressive disorders was higher among females than among males. The DALYs of depressive disorder accounted for a higher percentage of the total all-cause DALYs in the 10-64-year age group than in other age groups. Major depressive disorder was the largest contributor to the burden of depressive disorders. From 1990 to 2019, the crude prevalence and DALY rates per 100 000 population due to depressive disorders increased significantly, whereas age-standardised rates of prevalence and DALYs decreased significantly; the respective average annual percent changes were 0.88% (95% confidence interval: 0.87 to 0.89), 0.68% (0.66 to 0.70), -0.20% (-0.21 to -0.19), and -0.27% (-0.28 to -0.25). Although the age-standardised prevalence rate was lower than that seen globally, depressive disorders were considerable mental health issues in Vietnam. This study will help governments and policymakers to establish appropriate strategies to reduce the burden of these disorders by identifying the priority areas and individuals.

DOI： 10.1016/j.jpsychires.2024.02.041

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Calcium polystyrene sulfonate-induced rectal ulcer causing E. coli native-valve infective endocarditis. Reviewed

Shinnosuke Fukushima, Hideharu Hagiya, Hiroyuki Honda, Tomoharu Ishida, Ryohei Shoji, Kou Hasegawa, Fumio Otsuka

Clinical journal of gastroenterology   17 ( 3 )   472 - 476   2024.3

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Escherichia coli-associated native-valve infective endocarditis is a rare disease that affects elderly patients with underlying risk factors such as diabetes mellitus, malignancy, and renal failure. Long-term use of calcium polystyrene sulfonate is a potential risk factor for gastrointestinal mucosal damage or even colorectal ulcers. Herein, we describe a fatal case of a 66-year-old Japanese man with diabetes mellitus and renal failure who was prescribed calcium polystyrene sulfonate (CPS) for 11 years and developed a CPS-induced rectal ulcer, leading to E. coli native-valve infective endocarditis. The patient was admitted to our hospital due to acute-onset impaired consciousness. As a result of the systemic investigation, he was diagnosed with E. coli bacteremia accompanied by multiple cerebral infarctions and an acute hemorrhagic rectal ulcer. Transesophageal echocardiography revealed a 20-mm vegetative structure on the mitral valve, resulting in a final diagnosis of E. coli-associated infective endocarditis. After rectal resection, mitral valve replacement surgery was performed; however, the patient died shortly after surgery. Pathological findings of the resected rectum showed deposition of a basophilic crystalline material suggesting the presence of CPS. Our case highlights the potential risk of colorectal ulcers in a long-term CPS user, which can trigger bacterial translocation and endocarditis as fatal complications.

DOI： 10.1007/s12328-024-01949-4

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Zinc deficiency is a potential risk factor for COVID-19 progression to pneumonia requiring oxygen therapy. Reviewed International journal

Koji Fujita, Kazuki Ocho, Tomoka Kadowaki, Takashi Yorifuji, Hideharu Hagiya, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   30 ( 10 )   978 - 982   2024.3

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INTRODUCTION: Various risk factors for developing severe coronavirus disease 2019 (COVID-19) have been reported. However, studies on the nutritional-related risk factors are limited. In this study, we investigated the effects of serum zinc deficiency on the severity of COVID-19. METHODS: The study included a total of 60 COVID-19 patients who were admitted to Tsuyama Chuo Hospital between March 2020 and April 2021. We divided the patients into two categories based on serum levels of zinc (normal and latent zinc deficiency vs. zinc deficiency [<60 μg/dL]) at the time of diagnosis. Severity of COVID-19 was defined as the most exaggerated disease status during admission. The associations between serum zinc deficiency and the severity of COVID-19 were examined using a logistic regression model adjusted for potential confounders. RESULTS: Patients who required oxygen therapy had a higher prevalence of comorbidities and poorer nutritional status, including zinc deficiency, than those who did not require oxygen therapy. Zinc deficiency was associated with an increased risk of COVID-19 severity, with an adjusted odds ratio of 7.29 (95% confidence interval: 1.70-31.18). This result remained significant in the sensitivity analyses conducted after adjusting for patient background factors. CONCLUSIONS: Zinc deficiency at the time of COVID-19 diagnosis is an independent risk factor for severe disease. Our findings need to be validated in external studies.

DOI： 10.1016/j.jiac.2024.03.007

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Occult endocrine disorders newly diagnosed in patients with post-COVID-19 symptoms. Reviewed International journal

Yasuhiro Nakano, Naruhiko Sunada, Kazuki Tokumasu, Hiroyuki Honda, Yuki Otsuka, Yasue Sakurada, Yui Matsuda, Toru Hasegawa, Daisuke Omura, Kanako Ochi, Miho Yasuda, Hideharu Hagiya, Keigo Ueda, Fumio Otsuka

Scientific reports   14 ( 1 )   5446 - 5446   2024.3

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Determination of long COVID requires ruling out alternative diagnoses, but there has been no report on the features of alternative diagnoses. This study was a single-center retrospective study of outpatients who visited our clinic between February 2021 and June 2023 that was carried out to determine the characteristics of alternative diagnoses in patients with post-COVID-19 symptoms. In a total of 731 patients, 50 patients (6.8%) were newly diagnosed with 52 diseases requiring medical intervention, and 16 (32%) of those 50 patients (2.2% of the total) were considered to have priority for treatment of the newly diagnosed disorders over long COVID treatment. The proportion of patients with a new diagnosis increased with advance of age, with 15.7% of the patients aged 60 years or older having a new diagnosis. Endocrine and metabolic diseases and hematological and respiratory diseases were the most common, being detected in eight patients (16%) each. Although 35 of the 52 diseases (67%) were related to their symptoms, endocrine and metabolic diseases were the least associated with specific symptoms. Other disorders that require attention were found especially in elderly patients with symptomatic long COVID. Thus, appropriate assessment and differentiation from alternative diagnoses are necessary for managing long COVID.

DOI： 10.1038/s41598-024-55526-3

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SARS-CoV-2ワクチン接種後の持続的な副反応の特徴 副反応外来における後向き観察研究

徳増 一樹, 山下 茉奈美, 砂田 匠彦, 櫻田 泰江, 山本 紘一郎, 中野 靖浩, 松田 祐依, 大塚 勇輝, 長谷川 徹, 萩谷 英大, 本多 寛之, 大塚 文男

日本病院総合診療医学会雑誌   20 ( 臨増1 )   143 - 143   2024.3

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Penile cavernosal abscess after urethral injury Reviewed International journal

Koichiro Yamamoto, Hiroyuki Honda, Kou Hasegawa, Hideharu Hagiya, Fumio Otsuka

Clinical Case Reports   12 ( 2 )   e8534   2024.2

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Key Clinical Message

We present a patient catheterized for prostatic lesions who developed sepsis of urinary origin with a penile cavernosal abscess due to urethral injury caused by catheter ballooning. Urethral injury might lead to a life‐threatening penile abscess.

DOI： 10.1002/ccr3.8534

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Characteristics of Functional Hyperthermia Detected in an Outpatient Clinic for Fever of Unknown Origin. Reviewed International journal

Kosuke Oka, Kazuki Tokumasu, Hideharu Hagiya, Fumio Otsuka

Journal of clinical medicine   13 ( 3 )   2024.2

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Background: Functional hyperthermia (FH) is characterized by hyperthermia resulting from sympathetic hyperactivity rather than inflammation, and it is frequently overlooked by medical practitioners due to the absence of abnormalities in a medical examination. Although FH is an important differential diagnosis for fever of unknown origin (FUO), the literature on FUO cases in Japan lacks information on FH. In this study, we aimed to uncover the population of FH patients hidden in FUO cases. Methods: An outpatient clinic for FUO was established at Okayama University Hospital, and 132 patients were examined during the period from May 2019 to February 2022. Results: A diagnosis of FH was made in 31.1% of the FUO cases, and FH predominantly affected individuals in their third and fourth decades of life with a higher incidence in females (68.3%). The frequency of a history of psychiatric illness was higher in patients with FH than in patients with other febrile illnesses. Although the C-reactive protein (CRP) is generally negative in FH cases, some obese patients, with a body mass index ≥ 25 had slightly elevated levels of CRP but were diagnosed with FH. Conclusions: The results showed the importance of identifying FH when encountering patients with FUO without any organic etiology.

DOI： 10.3390/jcm13030889

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Detection of imported clinical strain of blaNDM-1-harbouring ST147 Klebsiella pneumoniae from a Ukrainian immigrant. Reviewed International journal

Shinnosuke Fukushima, Hideharu Hagiya, Kazuyoshi Gotoh, Shuma Tsuji, Koji Iio, Osamu Matsushita

Journal of travel medicine   31 ( 6 )   2024.1

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DOI： 10.1093/jtm/taae011

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Trends in the Incidence of Disseminated Cryptococcosis in Japan: A Nationwide Observational Study, 2015-2021. Reviewed International journal

Hidemasa Akazawa, Hideharu Hagiya, Toshihiro Koyama, Fumio Otsuka

Mycopathologia   189 ( 1 )   8 - 8   2024.1

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BACKGROUND: Cryptococcus species can cause severe disseminated infections in immunocompromised hosts. This study investigated the epidemiological features and trends in disseminated cryptococcosis in Japan. METHODS: We used publicly available Infectious Diseases Weekly Reports to obtain data on the incidence of disseminated cryptococcosis in Japan from 2015 to 2021. Patient information, including age, sex, and regional and seasonal data, were extracted. The Joinpoint regression program was used to determine the age-adjusted incidence rate (AAR) per 100,000 population, annual percentage change (APC), and average APC (AAPC). RESULTS: A total of 1047 cases of disseminated cryptococcosis were reported, of which those aged ≥ 70 years accounted for 68.8%. The AAR in men was significantly higher than that in women (median: 0.13 vs. 0.09: p = 0.0024). APC for the overall cases increased by 9.9% (95% confidence interval [95% CI] - 5.4-27.7) from 2015 to 2018 and then decreased by 3.3% (95% CI - 15.5-10.7) from 2018 to 2021. AAPC for the entire study period was 3.1% (95% CI - 1.5-8.0), indicating a possible increase in its number, although not statistically significant. In terms of regional distribution, the average AAR was highest in Shikoku District (0.17) and lowest in Hokkaido District (0.04). Northern Japan exhibited a significantly lower median AAR (median [interquartile range]: 0.06 [0.05, 0.08]) than the Eastern (0.12 [0.12, 0.13]), Western (0.11 [0.10, 0.13]), and Southern (0.14 [0.12, 0.15]) regions. No seasonal variation in incidence was observed. CONCLUSION: The prevalence of disseminated cryptococcosis has not increased in Japan. Geographically, the incidence is lower in Northern Japan. Further investigations that incorporate detailed clinical data are required.

DOI： 10.1007/s11046-023-00814-1

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本邦の小児肥満有病率の10年間の推移 Joinpoint regressionを用いた小児肥満トレンド解析

藤原 進太郎, 原田 洸, 萩谷 英大, 小山 敏広, 長谷川 高誠, 塚原 宏一, 大塚 文男

日本内分泌学会雑誌   99 ( 4 )   1052 - 1052   2024.1

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Development of virtual reality educational clips for improving hand hygiene compliance among healthcare providers: a pilot study Reviewed

Hideharu Hagiya, Shuichi Tanaka, Yuki Otsuka, Fumio Otsuka

Teaching and Learning in Nursing   19 ( 1 )   e17 - e20   2024.1

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DOI： 10.1016/j.teln.2023.08.004

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In vitro Activity of Cefmetazole and Flomoxef among Extended-Spectrum Beta-Lactamase producing Enterobacterales. Reviewed International journal

Koji Iio, Hideharu Hagiya, Tsukasa Higashionna, Fumio Otsuka

The new microbiologica   46 ( 4 )   348 - 353   2024.1

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In this age of antimicrobial resistance (AMR), improving treatment using existing antibiotics is desirable. Extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales (ESBL-E) are high priority AMR pathogens according to the World Health Organization. Cephamycin-class beta- lactams are tolerant to hydrolysis by ESBL activity and have bactericidal effects on ESBL-E. The aim of the present study was to compare the in vitro minimum inhibitory concentration (MIC) of cefmetazole (CMZ) and flomoxef (FMOX) among ESBL-E strains. This was a retrospective study using microbiology laboratory data from Okayama University Hospital (Japan) from January 2014 to June 2022. The MIC was determined by broth microdilution method and the ESBL phenotypes were determined by double-disk method. Antimicrobial use density (AUD) data for CMZ and FMOX were also gathered. Annual proportions of ESBL-producing organisms in Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae complex were 20.4-30.6%, 3.5-13.7%, and 0-3.1%, respectively. The ESBL-producing bacteria with MIC levels ≤1 μg/mL for CMZ and FMOX ranged from 57 to 84% and 97 to 100%, respectively, for E. coli, and from 50 to 92% and 80 to 100%, respectively, for K. pneumoniae. E. cloacae strains showed MIC levels ≥32 μg/mL for both agents. The AUD ratio for CMZ to FMOX ranged from 5.31 to 12.27, with no apparent upward or downward trend. Proportions of ESBL-producing E. coli and K. pneumoniae strains with MIC ≤1 μg/mL were greater in FMOX than in CMZ. To corroborate the clinical superiority of FMOX in treating ESBL-E infections, a randomized controlled study, as well as pharmacokinetic/pharmacodynamic analysis, is required.

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Changes in the place of death before and during the COVID-19 pandemic in Japan. Reviewed International journal

Masashi Shibata, Yuki Otsuka, Hideharu Hagiya, Toshihiro Koyama, Hideyuki Kashiwagi, Fumio Otsuka

PloS one   19 ( 2 )   e0299700   2024

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BACKGROUND: In the global aging, the coronavirus disease 2019 (COVID-19) pandemic may have affected the place of death (PoD) in Japan, where hospital deaths have dominated for decades. We analyzed the PoD trends before and during the COVID-19 pandemic in Japan. METHODS: This nationwide observational study used vital statistics based on death certificates from Japan between 1951 and 2021. The proportion of PoD; deaths at home, hospitals, and nursing homes; and annual percentage change (APC) were estimated using joinpoint regression analysis. Analyses were stratified by age groups and causes of death. RESULTS: After 2019, home deaths exhibited upward trends, while hospital death turned into downward trends. By age, no significant trend change was seen in the 0-19 age group, while hospital deaths decreased in the 20-64 age group in 2019. The trend change in home death in the ≥65 age group significantly increased since 2019 with an APC of 12.3% (95% confidence interval [CI]: 9.0 to 15.7), while their hospital death trends decreased by -4.0% (95% CI: -4.9 to -3.1) in 2019-2021. By cause of death, home death due to cancer and the old age increased since 2019 with an APC of 29.3% (95% CI: 25.4 to 33.2) and 8.8% (95% CI: 5.5 to 12.2), respectively. CONCLUSION: PoD has shifted from hospital to home during the COVID-19 pandemic in Japan. The majority of whom were older population with cancer or old age.

DOI： 10.1371/journal.pone.0299700

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Examination of yield, bacteriolytic activity and cold storage of linker deletion mutants based on endolysin S6_ORF93 derived from Staphylococcus giant bacteriophage S6. Reviewed International journal

Sosuke Munetomo, Jumpei Uchiyama, Iyo Takemura-Uchiyama, Thamonwan Wanganuttara, Yumiko Yamamoto, Toshihiro Tsukui, Hideharu Hagiya, Shuji Kanamaru, Hideyuki Kanda, Osamu Matsushita

PloS one   19 ( 10 )   e0310962   2024

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Methicillin-resistant Staphylococcus spp. present challenges in clinical and veterinary settings because effective antimicrobial agents are limited. Phage-encoded peptidoglycan-degrading enzyme, endolysin, is expected to be a novel antimicrobial agent. The enzymatic activity has recently been shown to be influenced by the linker between functional domains in the enzyme. S6_ORF93 (ORF93) is one of the endolysins derived from previously isolated Staphylococcus giant phage S6. The ORF93 was speculated to have a catalytic and peptidoglycan-binding domain with a long linker. In this study, we examined the influence of linker shortening on the characteristics of ORF93. We produce wild-type ORF93 and the linker deletion mutants using an Escherichia coli expression system. These mutants were designated as ORF93-Δ05, ORF93-Δ10, ORF93-Δ15, and ORF93-Δ20, from which 5, 10, 15, and 20 amino acids were removed from the linker, respectively. Except for the ORF93-Δ20, ORF93 and its mutants were expressed as soluble proteins. Moreover, ORF93-Δ15 showed the highest yield and bacteriolytic activity, while the antimicrobial spectrum was homologous. The cold storage experiment showed a slight effect by the linker deletion. According to our results and other studies, linker investigations are crucial in endolysin development.

DOI： 10.1371/journal.pone.0310962

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Trends in childhood obesity in Japan: A nationwide observational study from 2012 to 2021. Reviewed International journal

Shintaro Fujiwara, Ko Harada, Hideharu Hagiya, Toshihiro Koyama, Kosei Hasegawa, Hirokazu Tsukahara, Fumio Otsuka

Clinical obesity   14 ( 2 )   e12636   2023.12

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The persistent ascension of childhood obesity on a global scale constitutes a significant quandary. The prevalence of childhood obesity in Japan peaked in the early 2000s and has been reported to have declined since then, but recent data and its trend including the novel coronavirus disease 2019 (COVID-19) pandemic era are not available. Moreover, there is a dearth of studies examining the correlation between the trend in childhood obesity and exercise habits over the past decade. This study aims to examine the changes in the prevalence of obesity, physical fitness, and exercise habits over the past 10 years in Japanese children. We investigated the prevalence of childhood obesity in Japan, using the School Health Statistics Survey data from 2012 to 2021. The dataset has a sample size representative of children nationwide and includes variables for obesity, such as height, weight, and age. Data were classified into groups by sex and age (6-8, 9-11, and 12-14 years age). Children weighing 20% or more of the standard body weight are classified as obese. The annual percentage changes and average annual percentage changes were estimated using the joinpoint regression model. We also examined the trends in the physical fitness test score and exercise time. Average annual percentage changes of boys increased, especially in the 6- to 8-year age group (3.4%-4.6%). For girls, average annual percentage changes had increased in 6- to 8-year (2.5%-4.0%) and 9- to 11-year (0.9%-2.2%) age groups. Since the late 2010s, significantly increasing annual percentage changes were observed in 12- to 14-year age boys (6.7%-8.9%) and girls of many age groups (2.6%-8.6%). The physical fitness test score and exercise time showed decreasing trends since the late 2010s. Childhood obesity may have generally risen in Japan, in the last decade. Encouraging healthy eating and physical activity through school policies and curricula is necessary.

DOI： 10.1111/cob.12636

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International Trends in Adverse Drug Event-Related Mortality from 2001 to 2019: An Analysis of the World Health Organization Mortality Database from 54 Countries. Reviewed International journal

Toshihiro Koyama, Shunya Iinuma, Michio Yamamoto, Takahiro Niimura, Yuka Osaki, Sayoko Nishimura, Ko Harada, Yoshito Zamami, Hideharu Hagiya

Drug safety   47 ( 3 )   237 - 249   2023.12

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BACKGROUND AND OBJECTIVE: Adverse drug events (ADEs) are becoming a significant public health issue. However, reports on ADE-related mortality are limited to national-level evaluations. Therefore, we aimed to reveal overall trends in ADE-related mortality across the 21st century on an international level. METHODS: This observational study analysed long-term trends in ADE-related mortality rates from 2001 to 2019 using the World Health Organization Mortality Database. The rates were analysed according to sex, age and region. North America, Latin America and the Caribbean, Western Europe, Eastern Europe and Western Pacific regions were assessed. Fifty-four countries were included with four-character International Statistical Classification of Disease and Related Health Problems, Tenth Revision codes in the database, population data in the World Population Prospects 2019 report, mortality data in more than half of the study period, and high-quality or medium-quality death registration data. A locally weighted regression curve was used to show international trends in age-standardised rates. RESULTS: The global ADE-related mortality rate per 100,000 population increased from 2.05 (95% confidence interval 0.92-3.18) in 2001 to 6.86 (95% confidence interval 5.76-7.95) in 2019. Mortality rates were higher among men than among women, especially in those aged 20-50 years. The population aged ≥ 75 years had higher ADE-related mortality rates than the younger population. North America had the highest mortality rate among the five regions. The global ADE-related mortality rate increased by approximately 3.3-fold from 2001 to 2019. CONCLUSIONS: The burden of ADEs has increased internationally with rising mortality rates. Establishing pharmacovigilance systems can facilitate efforts to reduce ADE-related mortality rates globally.

DOI： 10.1007/s40264-023-01387-0

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Review of a Series of Surveys on Adverse Reactions to the COVID-19 mRNA-1273 Vaccine at Okayama University. Reviewed

Naomi Matsumoto, Chigusa Higuchi, Chikara Miyaji, Toshiharu Mitsuhashi, Hideharu Hagiya, Soshi Takao, Takashi Yorifuji

Acta medica Okayama   77 ( 6 )   567 - 575   2023.12

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This paper presents the results of a series of surveys conducted from July 2021 to March 2023 to investigate the post-vaccination adverse reactions to the mRNA-1273 (Moderna) vaccine among faculty, staff, and students at Okayama University. These studies complement the official surveys conducted by the Ministry of Health, Labour and Welfare (MHLW) and provide a more representative picture of adverse reactions in the general population including large numbers of healthy young people. Pain, swelling, redness at the injection site, fever, headache, and malaise were the main adverse reactions reported. The proportion of adverse reactions was generally higher after the second vaccination and decreased with each additional vaccination. No statistically significant differences in the adverse reactions were found for males and females and those with/without a history of allergy, but a lower proportion of fever was observed in older participants and those with underlying medical conditions. We also evaluated the association between adverse reactions and antibody titers after the third vaccination and found no significant differences in antibody levels one month after vaccination. This series of studies highlights the importance of conducting surveys in diverse populations to provide a more representative picture of post-vaccination adverse reactions during a pandemic.

DOI： 10.18926/AMO/66148

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当院におけるメチシリン感受性黄色ブドウ球菌のイノキュラムエフェクト陽性率

福島 伸乃介, 後藤 和義, 萩谷 英大, 飯尾 耕治, 松下 治

日本臨床微生物学会雑誌   34 ( Suppl.1 )   280 - 280   2023.12

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The effectiveness of simulation-based education combined with peer-assisted learning on clinical performance of first-year medical residents: a case-control study Reviewed International journal

Taku Murakami, Akira Yamamoto, Hideharu Hagiya, Mikako Obika, Yasuhiro Mandai, Tomoko Miyoshi, Hitomi Kataoka, Fumio Otsuka

BMC Medical Education   23 ( 1 )   859 - 859   2023.11

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Abstract

Background

Simulation-based education and peer-assisted learning (PAL) are both known as useful educational methods. Previous research has reported that combining these two methods are effective for training medical residents in short-term evaluation. This study was aimed to evaluate the middle- to long-term effects of simulation-based education combined with PAL on the performance of medical residents during emergency department duties.

Methods

This study was designed as a case-control study and conducted over three years at Okayama University Hospital in Japan. Postgraduate-year-one medical residents were assigned to three groups: a simulation group that received simulation-based education, a lecture group that received traditional lecture-based education, and a control group that received no such prior trainings. Prior training in emergency department duties using PAL was performed as an educational intervention for the simulation and lecture groups during the clinical orientation period. The residents’ medical knowledge was assessed by written examinations before and after the orientation. The performance of residents during their emergency department duties was assessed by self-evaluation questionnaires and objective-assessment checklists, following up with the residents for three months after the orientation period and collecting data on their 1st, 2nd, and 3rd emergency department duties. All the datasets collected were statistically analyzed and compared by their mean values among the three groups.

Results

A total of 75 residents were included in the comparative study: 27 in the simulation group, 24 in the lecture group, and 24 in the control group. The simulation and lecture groups obtained significantly higher written examination scores than the control group. From the self-evaluation questionnaires, the simulation group reported significantly higher satisfaction in their prior training than the lecture group. No significant differences were found in the emergency department performance of the residents among the three groups. However, when evaluating the improvement rate of performance over time, all three groups showed improvement in the subjective evaluation, and only the simulation and lecture groups showed improvement in the objective evaluation.

Conclusion

Simulation-based education combined with PAL is effective in improving the knowledge and satisfaction of medical residents, suggesting the possibility of improving work performance during their emergency department duties.

DOI： 10.1186/s12909-023-04798-w

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Other Link： https://link.springer.com/article/10.1186/s12909-023-04798-w/fulltext.html

Characteristics of Persistent Symptoms Manifested after SARS-CoV-2 Vaccination: An Observational Retrospective Study in a Specialized Clinic for Vaccination-Related Adverse Events Reviewed International journal

Kazuki Tokumasu, Manami Fujita-Yamashita, Naruhiko Sunada, Yasue Sakurada, Koichiro Yamamoto, Yasuhiro Nakano, Yui Matsuda, Yuki Otsuka, Toru Hasegawa, Hideharu Hagiya, Hiroyuki Honda, Fumio Otsuka

Vaccines   11 ( 11 )   1661 - 1661   2023.10

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Background: Although many adverse reactions after SARS-CoV-2 vaccination have been reported, there have been few comprehensive studies on persistent symptoms after SARS-CoV-2 vaccination. The aim of this study was to determine the clinical characteristics of patients with various persistent symptoms after SARS-CoV-2 vaccination. Methods: A retrospective descriptive study was performed for patients who visited a specialized clinic established at Okayama University Hospital to evaluate adverse events after SARS-CoV-2 vaccination during the period from April 2021 to March 2023. Results: Descriptive analysis was performed for 121 of 127 patients who visited the clinic during the study period, and separate analysis was performed for the other 6 patients who had serious complications, who required treatment with prednisolone, and who had persistent symptoms. The median [interquartile range] age of the patients was 48 years [31–64 years], and the patients included 44 males (36.4%) and 77 females (63.6%). The most frequent symptoms were sensory impairment (34 patients, 28.1%), general fatigue (30 patients, 24.8%), fever/low-grade fever (21 patients, 17.4%), and headache (21 patients, 17.4%). Serious complications included myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), sarcoidosis, aseptic meningitis, neuromyelitis optica spectrum disorders (NMOSDs), tendon adhesions, and idiopathic thrombocytopenia. Conclusions: Although causal relationships were not determined, 15 persistent symptoms after SARS-CoV-2 vaccination were characterized. All of the symptoms had onset from 12 hours to one week after vaccination, with 10 symptoms persisting for 6 months or longer. The most frequent symptom was sensory impairment.

DOI： 10.3390/vaccines11111661

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Relevance of complement immunity with brain fog in patients with long COVID. Reviewed International journal

Hideharu Hagiya, Kazuki Tokumasu, Yuki Otsuka, Naruhiko Sunada, Yasuhiro Nakano, Hiroyuki Honda, Masanori Furukawa, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   2023.10

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INTRODUCTION: This study aimed to elucidate the prevalence and clinical characteristics of patients with long COVID (coronavirus disease 2019), especially focusing on 50% hemolytic complement activity (CH50). METHODS: This retrospective observational study focused on patients who visited Okayama University Hospital (Japan) for the treatment of long COVID between February 2021 and March 2023. CH50 levels were measured using liposome immunometric assay (Autokit CH50 Assay, FUJIFILM Wako Pure Chemical Corporation, Japan); high CH50 was defined as ≥59 U/mL. Univariate analyses assessed differences in the clinical background, long COVID symptoms, inflammatory markers, and clinical scores of patients with normal and high CH50. Logistic regression model investigated the association between high CH50 levels and these factors. RESULTS: Of 659 patients who visited our hospital, 478 patients were included. Of these, 284 (59.4%) patients had high CH50 levels. Poor concentration was significantly more frequent in the high CH50 group (7.2% vs. 13.7%), whereas no differences were observed in other subjective symptoms (fatigue, headache, insomnia, dyspnea, tiredness, and brain fog). Multivariate analysis was performed on factors that could be associated with poor concentration, suggesting a significant relationship to high CH50 levels (adjusted odds ratio [aOR], 2.70; 95% confidence interval [CI], 1.33-5.49). Also, high CH50 was significantly associated with brain fog (aOR, 1.66; 95% CI, 1.04-2.66). CONCLUSIONS: High CH50 levels were frequently reported in individuals with long COVID, indicating a relationship with brain fog. Future in-depth research should examine the pathological role and causal link between complement immunity and the development of long COVID.

DOI： 10.1016/j.jiac.2023.10.016

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Safety and usefulness of nebulized liposomal amphotericin B: Systematic scoping review. Reviewed International journal

Hideharu Hagiya, Yoshito Nishimura, Fumio Otsuka

Pulmonary pharmacology & therapeutics   82   102233 - 102233   2023.10

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PURPOSE: Invasive fungal infections potentially result in fatal outcomes in immunocompromised hosts. Compared to intravenous administration, a nebulization therapy can achieve a high concentration of drug delivered in the respiratory tract, without a systematic absorption. We herein summarized the study findings on the safety and clinical utility of nebulized liposomal amphotericin B therapy. METHODS: According to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with relevant keywords, including "inhaled liposomal amphotericin B″, "nebulized liposomal amphotericin B″, or "aerosolized liposomal amphotericin B″, from the inception of these databases to August 31, 2022. RESULTS: Of the 172 articles found, 27 articles, including 13 case reports, 11 observational studies, and 3 clinical trials, were selected. Generally, findings showed that nebulized liposomal amphotericin B treatment appeared to be safe and without severe adverse effects. We found an accumulated evidence for the safety, tolerability, and effectiveness of nebulized liposomal amphotericin B prophylaxis among lung transplantation recipients; however, a randomized controlled study has yet to be reported. Data on hemato-oncological patients are relatively scarce; however, a randomized controlled study suggested the prophylactic effect of nebulized liposomal amphotericin B on invasive pulmonary aspergillosis. Observational and randomized controlled studies to evaluate therapeutic efficacy of the nebulized liposomal amphotericin B therapy have not been performed. CONCLUSION: In conclusion, we found increasing evidence for the effectiveness of the inhalation therapy among patients after lung transplantation and with hemato-oncological diseases.

DOI： 10.1016/j.pupt.2023.102233

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Clinical Characteristics of Retroperitoneal Fibrosis Patients at a Tertiary Hospital in Japan. Reviewed

Miho Ando, Yoshihisa Hanayama, Yoshito Nishimura, Hideharu Hagiya, Fumio Otsuka

Acta medica Okayama   77 ( 5 )   527 - 536   2023.10

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Retroperitoneal fibrosis (RPF) is a rare cause of hydronephrosis and progressive renal dysfunction with unidentified origin. RPF is categorized into idiopathic RPF with/without immunoglobulin G4 (IgG4)-related disease (IgG4-RD), and secondary RPF. Identifying the underlying cause is challenging and often associated with delayed diagnosis or therapeutic interventions. We investigated RPF's clinical characteristics based on different etiologies and factors that may help distinguish the underlying causes. We analyzed the cases of 49 patients with RPF that was radiographically diagnosed at our institution (2008-2022). The cohort was 77.6% males; 75.5% had idiopathic RPF and 24.5% had secondary RPF. Among the idiopathic patients, 54.1% had IgG4-RD. The patients were likely to have abdominal pain, lower back pain/lumbago, and constitutional symptoms including generalized fatigue and fever. The idiopathic patients were likely to have higher serum IgG4 and IgG levels and lower serum C3 levels compared to secondary RPF. The IgG4-RPF patients were likely to have higher serum IgG4 levels and lower serum C-reactive protein, ferritin, and C3 levels compared to the idiopathic RPF patients without IgG4-RD. These findings might reflect underlying systemic inflammatory responses. Comprehensive laboratory testing, including serum inflammatory markers and immunological panels, is recommended for radiologically diagnosed RPF patients.

DOI： 10.18926/AMO/65975

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COVID-19罹患後症状の受診から診断に至った内分泌代謝疾患の検討

中野 靖浩, 砂田 匠彦, 長谷川 徹, 松田 祐依, 櫻田 泰江, 大塚 勇輝, 大村 大輔, 徳増 一樹, 本多 寛之, 越智 可奈子, 長谷川 功, 萩谷 英大, 植田 圭吾, 大塚 文男

日本内分泌学会雑誌   99 ( 2 )   562 - 562   2023.10

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新型コロナ後遺症にみられる睡眠障害とその内分泌変化の検討

砂田 匠彦, 中野 靖浩, 大塚 勇輝, 徳増 一樹, 本多 寛之, 櫻田 泰江, 松田 祐依, 長谷川 徹, 大村 大輔, 越智 可奈子, 萩谷 英大, 植田 圭吾, 片岡 仁美, 大塚 文男

日本内分泌学会雑誌   99 ( 2 )   584 - 584   2023.10

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Epidemiological Characteristics and Trends in the Incidence of Leptospirosis in Japan: A Nationwide, Observational Study from 2006 to 2021. Reviewed International journal

Hideharu Hagiya, Toshihiro Koyama, Fumio Otsuka

The American journal of tropical medicine and hygiene   109 ( 3 )   589 - 594   2023.9

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During this age of climate change, the incidence of tropical diseases may change. This study compared the epidemiological characteristics and trends of leptospirosis in Japan between the endemic region, Okinawa, and the rest of the country. Infectious Diseases Weekly Reports were used to determine the numbers and crude incidence rates of leptospirosis. Data were stratified by sex, age, the estimated location of the infection, the notified regions, and the reporting month. A joinpoint regression analysis was performed to estimate the annual percentage change (APC). During the 16-year study period (2006-2021), 543 leptospirosis cases were reported, with male dominance (86.2%). Approximately half of these cases were reported from Okinawa (47.1%). The patients were relatively younger in Okinawa (20-29 years, 23.4%; 30-39 years, 20.7%) than outside Okinawa. The frequency of imported cases was significantly higher outside Okinawa (0.4% versus 14.3%). The incidences of leptospirosis in and outside Okinawa were apparently higher during the summer and typhoon seasons. The annual crude incidence ratios were 20-200 times higher in Okinawa than in the rest of the country. The average APCs for the entire study period in Okinawa and the rest of Japan were 1.6% (95% CI: -5.9 to 9.6) and -1.8% (95% CI: -7.8 to 4.6), respectively, without any particular trends. Collectively, the patient profile of leptospirosis differed between Okinawa (younger men) and outside Okinawa (middle- or older-aged men with a history of traveling abroad). The disease remains a neglected tropical disease; continuous surveillance with close monitoring is required.

DOI： 10.4269/ajtmh.23-0131

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Case Report: Leptospirosis after a Typhoon Disaster Outside the Endemic Region, Japan. Reviewed International journal

Yukichika Yamamoto, Hideharu Hagiya, Ruiko Hayashi, Fumio Otsuka

The American journal of tropical medicine and hygiene   109 ( 3 )   587 - 588   2023.9

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Leptospirosis is a zoonotic disease that primarily affects people in tropical and subtropical areas worldwide. Owing to the temperate climate of Japan, leptospirosis is not endemic across the country. Domestic cases of leptospirosis have been mainly reported in Okinawa and the southwestern subtropical islands, but not in the other regions. Here, we describe a case of leptospirosis that developed and was diagnosed outside the domestically endemic region. Notably, disease onset occurred shortly after the patient experienced a flood after a typhoon disaster. With global warming, the international prevalence of leptospirosis may change. Physicians outside currently endemic areas must be aware of this tropical disease.

DOI： 10.4269/ajtmh.23-0133

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Super acute-onset disseminated BCG infection: A case report. Reviewed International journal

Ryosuke Takase, Hideharu Hagiya, Takumi Fujimori, Yukika Yokoyama, Koji Iio, Hiroyuki Honda, Kou Hasegawa, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   29 ( 9 )   919 - 921   2023.9

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Intravesical Bacillus Calmette-Guérin (BCG) instillation is an established immunotherapy for superficial bladder cancer. Herein, we describe a case of disseminated BCG infection that developed immediately after the first BCG injection. A 76-year-old man diagnosed with non-invasive bladder cancer underwent intravesical BCG instillation; he developed high fever and systemic arthralgia later that night. General examination did not reveal any infectious sources, and a combination therapy of isoniazid, rifabutin, and ethambutol was initiated after collecting his blood, urine, bone marrow, and liver biopsy samples for mycobacterial cultures. Three weeks later, Mycobacterium bovis was detected in the urine and bone marrow samples, and pathological investigation of liver biopsy revealed multiple small epithelial granulomas with focal multinucleated giant cells, leading to a diagnosis of disseminated BCG infection. The patient recovered after long-term antimycobacterial therapy without remarkable sequelae. Most cases of disseminated BCG infection occur after several doses of BCG injections, and its onset reportedly varies among cases, ranging from a few days to several months. The present case was notable as disease onset was observed only a few hours after the first BCG injection. Although rare, development of disseminated BCG infection should be considered as a differential diagnosis in patients at any time after intravesical BCG instillation therapy.

DOI： 10.1016/j.jiac.2023.05.017

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Task shifting of medical office works: A preliminary questionnaire survey for generalists. Reviewed

Yuki Otsuka, Hideharu Hagiya, Naruhiko Sunada, Fumio Otsuka

Journal of general and family medicine   24 ( 5 )   317 - 319   2023.9

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To reduce physician burden, task shifting of clerical work from physicians to medical assistants is being promoted; however, it depends on hospitals. A questionnaire survey was conducted among 40 general physicians at Okayama University Hospital in December 2022 to investigate physicians' preferences toward task shifting. Compared to other tasks, most physicians thought that ordering examinations (14, 47%), replying to referral letters (19, 63%), and prescriptions (21, 70%) and medical record entries (22, 73%) should not be task shifted. Physicians' controversial opinions on task shifting maybe the reason behind the slow progress in task shifting.

DOI： 10.1002/jgf2.641

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Increased evidence for no benefit of contact precautions in preventing extended-spectrum β-lactamases-producing Enterobacteriaceae: Systematic scoping review Reviewed International journal

Hideharu Hagiya, Fumio Otsuka

American Journal of Infection Control   51 ( 9 )   1056 - 1062   2023.9

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INTRODUCTION: Extended-spectrum β-lactamases-producing Enterobacteriaceae (ESBL-E) is a critical antimicrobial resistance pathogen, to which we need to pay the greatest attention. This study was aimed at uncovering the present evidence for the preventive effectiveness of contact precautions for patients colonized or infected with ESBL-E. METHODS: According to the Preferred Reporting Items for Systemic Reviews and Meta-analyses (PRISMA) Extension for Scoping Reviews, we searched MEDLINE for articles with relevant keywords from the beginning of 2010 to October 18, 2022. RESULTS: Of the 355 articles found, 9, including 8 observational studies and 1 randomized controlled trial, were selected. Safety of discontinuing contact precautions was evaluated mainly in acute-care and long-term care hospitals. Consistently, all authors concluded that contact precautions can be safely discontinued in patients colonized or infected with ESBL-E. CONCLUSION: The clinical impact of discontinuing contact precautions for patients with ESBL-E is minimal and can be safely withdrawn at acute, noncritical, adult care wards. Relevant data from pediatric and geriatric wards, as well as intensive care units, were insufficient and should be investigated in future research.

DOI： 10.1016/j.ajic.2023.01.018

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A clinical concern: Neisseria meningitidis as a reemerging pathogen with increased antimicrobial resistance. Reviewed International journal

Hideharu Hagiya, Koji Iio

European journal of neurology   30 ( 12 )   3986 - 3987   2023.8

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DOI： 10.1111/ene.16019

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Preoperative detection of functional somatostatin receptors in a patient with an insulinoma. Reviewed International journal

Kohei Oguni, Shinnosuke Fukushima, Yukichika Yamamoto, Kou Hasegawa, Hideharu Hagiya, Naoko Inoshita, Fumio Otsuka

Clinical case reports   11 ( 8 )   e7771   2023.8

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Octreotide is used in patients with insulinomas to treat hypoglycemia, and somatostatin receptor (SSTR) 2 expression is important for its efficacy. We report a case of insulinoma in a 50-year-old woman that responded to an octreotide test, showed accumulation in somatostatin scintigraphy, and was positive for SSTR2A on immunostaining.

DOI： 10.1002/ccr3.7771

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当院総合内科・総合診療科における後腹膜線維症49症例の特徴の検討

花山 宜久, 安藤 美穂, 西村 義人, 徳増 一樹, 長谷川 功, 萩谷 英大, 大塚 文男

日本病院総合診療医学会雑誌   19 ( 臨増2 )   163 - 163   2023.8

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褥瘡を伴う胸髄損傷患者に発症した腰部化膿性脊椎炎の1例

森田 悟, 加藤 篤之, 須山 敦仁, 佐藤 啓介, 佐住 洋祐, 大塚 勇輝, 大國 皓平, 大野 洋平, 長谷川 功, 本多 寛之, 萩谷 英大, 小田 孔明, 今村 竜太, 大塚 文男

日本病院総合診療医学会雑誌   19 ( 臨増2 )   180 - 180   2023.8

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眼内炎診療における病院総合医の役割

川口 満理奈, 大塚 勇輝, 副島 佳晃, 安藤 航, 高木 桃李, 大國 皓平, 長谷川 功, 本多 寛之, 萩谷 英大, 小比賀 美香子, 森田 哲郎, 森實 祐基, 大塚 文男

日本病院総合診療医学会雑誌   19 ( 臨増2 )   142 - 142   2023.8

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褥瘡を伴う胸髄損傷患者に発症した腰部化膿性脊椎炎の1例

森田 悟, 加藤 篤之, 須山 敦仁, 佐藤 啓介, 佐住 洋祐, 大塚 勇輝, 大國 皓平, 大野 洋平, 長谷川 功, 本多 寛之, 萩谷 英大, 小田 孔明, 今村 竜太, 大塚 文男

日本病院総合診療医学会雑誌   19 ( 臨増2 )   180 - 180   2023.8

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就学患者のCOVID-19罹患後症状とその社会的影響

櫻田 泰江, 大塚 勇輝, 徳増 一樹, 砂田 匠彦, 本多 寛之, 中野 靖浩, 松田 祐依, 萩谷 英大, 植田 圭吾, 大塚 文男

日本病院総合診療医学会雑誌   19 ( 臨増2 )   168 - 168   2023.8

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眼内炎診療における病院総合医の役割

川口 満理奈, 大塚 勇輝, 副島 佳晃, 安藤 航, 高木 桃李, 大國 皓平, 長谷川 功, 本多 寛之, 萩谷 英大, 小比賀 美香子, 森田 哲郎, 森實 祐基, 大塚 文男

日本病院総合診療医学会雑誌   19 ( 臨増2 )   142 - 142   2023.8

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MOCA-Jを用いたCOVID-19罹患後症状のブレインフォグの臨床的特徴の解明

長谷川 徹, 大塚 勇輝, 櫻田 泰江, 徳増 一樹, 砂田 匠彦, 小西 隆之, 中野 靖浩, 本多 寛之, 萩谷 英大, 小比賀 美香子, 植田 圭吾, 大塚 文男

日本病院総合診療医学会雑誌   19 ( 臨増2 )   168 - 168   2023.8

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不明熱診療にて遭遇した機能性高体温症とその臨床的特徴

岡 浩介, 徳増 一樹, 萩谷 英大, 大塚 文男

日本病院総合診療医学会雑誌   19 ( 臨増2 )   145 - 145   2023.8

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当院総合内科・総合診療科における後腹膜線維症49症例の特徴の検討

花山 宜久, 安藤 美穂, 西村 義人, 徳増 一樹, 長谷川 功, 萩谷 英大, 大塚 文男

日本病院総合診療医学会雑誌   19 ( 臨増2 )   163 - 163   2023.8

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Trends in Head and Neck Cancer Mortality from 1999 to 2019 in Japan: An Observational Analysis. Reviewed International journal

Tsukasa Higashionna, Keisaku Harada, Akinari Maruo, Takahiro Niimura, Elizabeth Tan, Quynh Thi Vu, Takayoshi Kawabata, Soichiro Ushio, Hirofumi Hamano, Makoto Kajizono, Yoshito Zamami, Keisuke Ishizawa, Ko Harada, Shiro Hinotsu, Mitsunobu R Kano, Hideharu Hagiya, Toshihiro Koyama

Cancers   15 ( 15 )   2023.7

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Globally, the numbers of head and neck cancer (HNC) cases and related deaths have recently increased. In Japan, few studies have examined crude or age-adjusted HNC mortality rates. Therefore, this study aimed to determine the trends in crude and age-adjusted mortality rates for HNC per million individuals in Japan from 1999 to 2019. Data on HNC-associated deaths were extracted from the national death certificate database using the International Classification of Diseases, Tenth Revision (n = 156,742). HNC mortality trends were analysed using joinpoint regression models to estimate annual percentage change (APC) and average APC (AAPC). Among men, no significant change was observed in the age-adjusted death rate trend from 1999 to 2014; however, a marked decrease was observed from 2014 to 2019. No changing point was observed in women. Age-adjusted mortality rates continuously decreased over the 21-year period, with an AAPC of -0.7% in men and -0.6% in women. In conclusion, the overall trend in age-adjusted rates of HNC-associated deaths decreased, particularly among men, in the past 5 years. These results will contribute to the formulation of medical policies to develop targeted screening and prevention programmes for HNC in Japan and determine the direction of treatment strategies.

DOI： 10.3390/cancers15153786

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Utility of Serum Ferritin for Predicting Myalgic Encephalomyelitis/Chronic Fatigue Syndrome in Patients with Long COVID. Reviewed International journal

Yukichika Yamamoto, Yuki Otsuka, Kazuki Tokumasu, Naruhiko Sunada, Yasuhiro Nakano, Hiroyuki Honda, Yasue Sakurada, Toru Hasegawa, Hideharu Hagiya, Fumio Otsuka

Journal of clinical medicine   12 ( 14 )   2023.7

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OBJECTIVE: The most common symptom of post-acute coronavirus disease 2019 (COVID-19) is fatigue, and it potentially leads to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS); however, a specific prognosticator is lacking. We aimed to elucidate the clinical characteristics of patients who developed ME/CFS after COVID-19. METHODS: In this retrospective observational study, patients who visited Okayama University Hospital for long COVID between February 2021 and March 2022 were investigated. RESULTS: Of the 234 patients, 139 (59.4%) had fatigue symptoms. Fifty patients with fatigue symptoms (21.4%) met the criteria for ME/CFS (ME/CFS group), while the other 89 patients did not (non-ME/CFS group); 95 patients had no fatigue complaints (no-fatigue group). Although the patients' backgrounds were not significantly different between the three groups, the ME/CFS group presented the highest scores on the self-rating symptom scales, including the Fatigue Assessment Scale (FAS), EuroQol, and the Self-Rating Depression Scale (SDS). Furthermore, serum ferritin levels, which were correlated with FAS and SDS scores, were significantly higher in the ME/CFS group (193.0 μg/L, interquartile range (IQR): 58.8-353.8) than in the non-ME/CFS group (98.2 μg/L, 40.4-251.5) and no-fatigue group (86.7 μg/L, 37.5-209.0), and a high serum ferritin level was prominent in female patients. Endocrine workup further showed that the ME/CFS group had higher thyrotropin levels but lower growth hormone levels in serum and that insulin-like growth factor-I levels were inversely correlated with ferritin levels (R = -0.328, p < 0.05). CONCLUSIONS: Serum ferritin level is a possible predictor of the development of ME/CFS related to long COVID, especially in female patients.

DOI： 10.3390/jcm12144737

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A Case of Typhoid Fever Presenting with Non-G6PD Associated Hemolytic Anemia Reviewed International journal

Shinnosuke Fukushima, Hideharu Hagiya, Hiroyuki Honda, Tomoharu Ishida, Kou Hasegawa, Fumio Otsuka

Journal of Travel Medicine   30 ( 6 )   2023.7

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Typhoid fever is one of the representative febrile diseases in tropical and subtropical countries with poor hygiene. Among the anaemic conditions involving patients with typhoid fever, autoimmune hemolytic anaemia would be one of the potential causes in the absence of G6PD deficiency or intestinal haemorrhage

DOI： 10.1093/jtm/taad092

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Endogenous panophthalmitis after colonoscopy. Reviewed International journal

Yukichika Yamamoto, Kohei Oguni, Hideharu Hagiya, Fumio Otuska

Internal and emergency medicine   2023.7

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DOI： 10.1007/s11739-023-03368-8

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Antiviral effect and safety of nafamostat mesilate in patients with mild early-onset COVID-19: An exploratory multicenter randomized controlled clinical trial. Reviewed International journal

Shu Okugawa, Mahoko Ikeda, Kosuke Kashiwabara, Takashi Moritoyo, Takao Kohsaka, Toshio Shimizu, Hideharu Hagiya, Kou Hasegawa, Fumio Otsuka, Ayumi Miwa, Nobuhito Kisimoto, Ayako Mizoguchi, Akira Imamura, Kazuhiko Ikeuchi, Takeya Tsutsumi, Daisuke Jubishi, Hideki Hashimoto, Koh Okamoto, Sohei Harada, Jun-Ichiro Inoue, Yasuyuki Seto, Kyoji Moriya

International journal of antimicrobial agents   62 ( 3 )   106922 - 106922   2023.7

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OBJECTIVES: This study aimed to evaluate the antiviral effects and safety of nafamostat in early-onset patients with coronavirus disease 2019 (COVID-19). METHODS: In this exploratory multicenter randomized controlled trial, patients were assigned to three groups within 5 days of symptom onset, with 10 participants in each group: nafamostat at either 0.2 mg/kg/h or 0.1 mg/kg/h or a standard-of-care group. The primary endpoint was area under the curve for decrease in SARS-CoV-2 viral load in nasopharyngeal samples from baseline to day 6. RESULTS: Of the 30 randomized patients, 19 received nafamostat. Overall, 10 patients received low-dose nafamostat, 9 patients received high-dose nafamostat, and 10 received standard-of-care. The detected viruses were Omicron strains. The regression coefficient for area under the curve for decrease in viral load as the response variable and nafamostat dose per body weight as the explanatory variable showed a significant relationship of -40.1 (95% confidence interval, -74.1 to -6.2; p=0.022). Serious adverse events were not observed in either group. Phlebitis occurred in approximately 50% of patients treated with nafamostat. CONCLUSIONS: Nafamostat exerts virus load-reducing effects in patients with early-onset COVID-19.

DOI： 10.1016/j.ijantimicag.2023.106922

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Practice of Zoning in pre-clinical medical students

越智可奈子, 萩谷英大, 小崎吉訓, 三好智子, 山下範之, 伊野英男, 成瀬恵治, 大塚文男, 松川昭博

医学教育   54 ( Suppl. )   296 - 296   2023.7

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Global trends of seasonal influenza-associated mortality in 2001-2018: A longitudinal epidemiological study. Reviewed International journal

Hideharu Hagiya, Yuka Osaki, Michio Yamamoto, Takahiro Niimura, Ko Harada, Tsukasa Higashionna, Hirofumi Hamano, Yoshito Zamami, Shiro Hinotsu, Toshihiro Koyama

The Journal of infection   87 ( 3 )   e54-e57   2023.6

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DOI： 10.1016/j.jinf.2023.06.011

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Current Prevalence of Antimicrobial Resistance in Okayama from a National Database between 2018 and 2021. Reviewed

Shinnosuke Fukushima, Hideharu Hagiya, Kazuhiro Uda, Kazuyoshi Gotoh, Fumio Otsuka

Acta medica Okayama   77 ( 3 )   255 - 262   2023.6

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Antimicrobial resistance is an emerging global threat that must be addressed using a multidisciplinary approach. This study aimed to raise awareness of high-level antimicrobial-resistant (AMR) pathogens in Japan by comparing their recent prevalences among prefectures, particularly Okayama. Data for the isolation proportions of meropenem-resistant Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae, and levofloxacin-resistant E. coli and K. pneumoniae were collected from the Japan Nosocomial Infections Surveillance, a national database sponsored by the Japanese Ministry of Health, Labour, and Welfare, between 2018 and 2021. The average isolated proportions of the seven AMR pathogens were higher in Okayama compared to other prefectures: the worst (19.9%) was meropenem-resistant P. aeruginosa, the sixth worst (57.2%) was methicillin-resistant S. aureus, the eighth worst (3.3%) was vancomycin-resistant E. faecium, the second (37.8%) and fifth worst (17.6%) were cefotaxime-resistant E. coli and K. pneumoniae, respectively, and the fourth (49.9%) and third worst (8.7%) were levofloxacin-resistant E. coli and K. pneumoniae, respectively. Our study highlights the notably high prevalences of representative AMR pathogens in Okayama, suggesting the need for fundamental infection prevention and control by healthcare professionals, promoting antimicrobial stewardship, and educating undergraduates and postgraduates in Okayama.

DOI： 10.18926/AMO/65490

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Manifestation of Headache Affecting Quality of Life in Long COVID Patients. Reviewed International journal

Kana Fujita, Yuki Otsuka, Naruhiko Sunada, Hiroyuki Honda, Kazuki Tokumasu, Yasuhiro Nakano, Yasue Sakurada, Mikako Obika, Hideharu Hagiya, Fumio Otsuka

Journal of clinical medicine   12 ( 10 )   2023.5

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Objectives: The present study aimed to elucidate the characteristics of long COVID patients with headaches. Methods: A single-center retrospective observational study was performed for long COVID outpatients who visited our hospital from 12 February 2021 to 30 November 2022. Results: A total of 482 long COVID patients, after excluding 6, were divided into two groups: the Headache group of patients with complaints of headache (113 patients: 23.4%) and the remaining Headache-free group. Patients in the Headache group were younger (median age: 37 years) than patients in the Headache-free group (42 years), while the ratio of females (56%) in the Headache group was nearly the same as that in the Headache-free group (54%). The proportion of patients in the Headache group who were infected in the Omicron-dominant phase (61%) was larger than the proportions of patients infected in the Delta (24%) and preceding (15%) phases, and that trend was significantly different from the trend in the Headache-free group. The duration before the first visit for long COVID was shorter in the Headache group (71 days) than in the Headache-free group (84 days). The proportions of patients in the Headache group with comorbid symptoms, including general fatigue (76.1%), insomnia (36.3%), dizziness (16.8%), fever (9.7%), and chest pain (5.3%) were larger than the proportions of patients in the Headache-free group, whereas blood biochemical data were not significantly different between the two groups. Interestingly, patients in the Headache group had significant deteriorations of scores indicating depression and scores for quality of life and general fatigue. In multivariate analysis, headache, insomnia, dizziness, lethargy, and numbness were shown to be involved in the quality of life (QOL) of long COVID patients. Conclusions: The manifestation of headaches related to long COVID was found to have a significant impact on social and psychological activities. Alleviation of headaches should be a priority for the effective treatment of long COVID.

DOI： 10.3390/jcm12103533

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Furious lung abscess due to Parvimonas micra Reviewed International journal

Shinnosuke Fukushima, Hideharu Hagiya, Hiromichi Naito, Fumio Otsuka

Respirology Case Reports   11 ( 6 )   e01161   2023.5

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Parvimonas micra commonly present in the oral cavity and intestinal tract of humans. P. micra indicating a high virulence, has the potential of forming abscess. The infection of P. micra may require surgical excision.

DOI： 10.1002/rcr2.1161

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Clinical Characteristics of Strongyloidiasis during the COVID-19 Pandemic: Systematic Scoping Review. Reviewed International journal

Manasawee Tanariyakul, Bolin Chang, Koichi Keitoku, Marissa Su, Hideharu Hagiya, Yoshito Nishimura

The American journal of tropical medicine and hygiene   108 ( 5 )   901 - 905   2023.5

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The clinical impact of Strongyloides stercoralis hyperinfection secondary to immunosuppressive therapy for coronavirus disease 2019 (COVID-19) has been an emerging topic of interest, although characteristics of Strongyloides infection in COVID-19 patients are not yet well characterized. This study summarizes the existing evidence of Strongyloides infection in COVID-19 patients and recommends future areas of research. According to the PRISMA Extension for Scoping Reviews, we performed a search on MEDLINE and EMBASE for articles with keywords including "Strongyloides," "Strongyloidiasis," and "COVID-19" from the inception of these databases to June 5, 2022. A total of 104 articles were found. After excluding duplication and thorough reviews, 11 articles, including two observational studies, one conference abstract, and nine case reports or series, were included. Two observational studies focused on revealing the prevalence of Strongyloides screening in COVID-19 patients and clinical follow-up. Among the included cases, patients were mostly from low- or middle-income countries and suffered from severe or critical COVID-19. Strongyloides hyperinfection and disseminated infection were reported in 60% and 20%, respectively. Interestingly, 40% did not have eosinophilia, a hallmark of parasitic infection, potentially leading to delay in diagnosis of strongyloidiasis. This systematic review summarizes the clinical characteristics of strongyloidiasis in COVID-19 infection. Although further studies to identify risks and precipitants associated with the onset of strongyloidiasis are crucial, increased awareness of the critical condition is warranted.

DOI： 10.4269/ajtmh.22-0671

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新型コロナウイルス後遺症診療において発見された内分泌代謝疾患

中野 靖浩, 副島 佳晃, 田中 秀一, 大塚 勇輝, 徳増 一樹, 本多 寛之, 長谷川 功, 萩谷 英大, 大塚 文男

日本内分泌学会雑誌   99 ( 1 )   323 - 323   2023.5

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新型コロナウイルス後遺症診療において発見された内分泌代謝疾患

中野 靖浩, 副島 佳晃, 田中 秀一, 大塚 勇輝, 徳増 一樹, 本多 寛之, 長谷川 功, 萩谷 英大, 大塚 文男

日本内分泌学会雑誌   99 ( 1 )   323 - 323   2023.5

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Susceptibility of ceftolozane/tazobactam against multidrug-resistant and carbapenem-resistant Pseudomonas aeruginosa. Reviewed International journal

Ayaka Kakehi, Hideharu Hagiya, Koji Iio, Takumi Fujimori, Mami Okura, Hiroshi Minabe, Yukika Yokoyama, Fumio Otsuka, Akihito Higashikage

The new microbiologica   46 ( 2 )   213 - 215   2023.5

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Ceftolozane (CTLZ) is a novel cephalosporin antibiotic that exhibits broad-spectrum activity against gram-negative pathogens, including Pseudomonas aeruginosa, especially when combined with tazobactam (TAZ). We examined the minimum inhibitory concentration (MIC) of CTLZ/TAZ for 21 multidrug-resistant P. aeruginosa (MDRP) and eight carbapenem-resistant P. aeruginosa (CRPA) strains isolated at Okayama University Hospital, Japan. Consequently, 81% (17/21) of the MDRP strains and 25% (2/8) of the CRPA strains were resistant to CTLZ/TAZ (MIC >8 μg/mL). All 18 blaIMP-positive strains showed resistance to CTLZ/TAZ, whereas the drug retained in vitro susceptibility in 54.5% (6/11 strains) of blaIMP-negative strains.

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Like a shot-through manubrium: A rare presentation of skeletal tuberculosis. Reviewed International journal

Tomohiro Fujiwara, Hiroyuki Yanai, Hideharu Hagiya

Clinical case reports   11 ( 5 )   e7119   2023.5

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A 22-year-old Vietnamese woman presented with anterior chest swelling. Computed tomography revealed an osteolytic lesion in the manubrium, whereas MRI showed an extra-osseous expansion. A needle biopsy showed granuloma formation, whereas a 3-week mycobacterial culture indicated Mycobacterium tuberculosis infection. Manubrium/sternum involvement in tuberculosis is extremely rare but should be considered.

DOI： 10.1002/ccr3.7119

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高齢者のセザリー症候群に対してインターフェロンγが奏功した1例

澤井 希望, 三宅 智子, 徳田 真優, 佐藤 志帆, 立花 宏太, 杉本 佐江子, 川上 佳夫, 森実 真, 萩谷 英大, 淺田 騰

日本皮膚科学会雑誌   133 ( 5 )   1411 - 1411   2023.5

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Case Series of Granulicatella Bacteremia: A Single-centered, Five-year Retrospective Study. Reviewed

Shinnosuke Fukushima, Hideharu Hagiya, Koji Iio, Hiroyuki Honda, Tomoharu Ishida, Hirokazu Nagaoka, Kou Hasegawa, Fumio Otsuka

Acta medica Okayama   77 ( 2 )   203 - 207   2023.4

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Granulicatella species are rare, nutritionally variant streptococci that cause infective endocarditis. Their clinical and microbiological characteristics remain unknown. We reviewed five years of Granulicatella cases in our hospital database (Jan 2017-Jun 2022), finding 6 Granulicatella adiacens cases and 1 Granulicatella elegans case. Clinical backgrounds and bacteremia sources were diverse; 3 cases developed polymicrobial bacteremia. Antimicrobial testing showed non-susceptibility to penicillin G in 4 of 7 cases (57.1%), and high susceptibility to carbapenems and vancomycin in all cases. Determining optimal antibiotic therapy for Granulicatella infections is vital in this era of antimicrobial resistance.

DOI： 10.18926/AMO/65151

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Letter to the Editor: A Need for Infectious Disease Specialists in Public Healthcare Centers? Reviewed International journal

Hideharu Hagiya

Journal of Korean medical science   38 ( 9 )   e84   2023.3

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DOI： 10.3346/jkms.2023.38.e84

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ハンセン病に対する免疫抑制療法を背景に発症した播種性糞線虫症の1例 Reviewed

中本 健太, 萩谷 英大, 平 佑貴, 庵谷 紘美, 中野 靖浩, 長谷川 功, 大塚 文男

感染症学雑誌   97 ( 2 )   52 - 57   2023.3

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症例は30歳代ネパール人男性で、下痢と嘔気を主訴とした。ハンセン病(LL型)と新型コロナウイルス感染症の既往があり、らい反応に対して長期間のステロイド製剤内服による免疫抑制療法を行っていた。各種検査所見より、糞線虫の過剰感染状態による播種性糞線虫症と診断した。栄養状態は不良で、寄生虫の消化管内過剰増殖に伴う腸管浮腫を認め、イベルメクチンは吸収不良で血中濃度が不十分であった。多臓器不全を併発したため集学的治療を行ったが第36病日に死亡した。日本では糞線虫症は稀であるが、インバウンドの増加に伴い播種性糞線虫症のリスクが増加する可能性があり、ステロイドの長期内服などで免疫抑制状態の可能性がある場合は寄生虫スクリーニングを行う必要があると考えられた。

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Buruli ulcer caused by Mycobacterium ulcerans subsp. shinshuense: A case report. Reviewed International journal

Takumi Fujimori, Hideharu Hagiya, Koji Iio, Osamu Yamasaki, Yuji Miyamoto, Yoshihiko Hoshino, Ayaka Kakehi, Mami Okura, Hiroshi Minabe, Yukika Yokoyama, Fumio Otsuka, Akihito Higashikage

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   29 ( 5 )   523 - 526   2023.2

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Buruli ulcer is the third most common mycobacterial infection worldwide and is mainly diagnosed in tropical regions. Globally, this progressive disease is caused by Mycobacterium ulcerans; however, Mycobacterium ulcerans subsp. shinshuense, an Asian variant, has been exclusively identified in Japan. Because of insufficient clinical cases, the clinical features of M. ulcerans subsp. shinshuense-associated Buruli ulcer remain unclear. A 70-year-old Japanese woman presented with erythema on her left backhand. The skin lesion deteriorated without an apparent etiology of inflammation, and she was referred to our hospital 3 months after disease onset. A biopsy specimen was incubated in 2% Ogawa medium at 30 °C. After 66 days, we detected small yellow-pigmented colonies, suggesting scotochromogens. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI Biotyper; Bruker Daltonics, Billerica, MA, USA) indicated that the organism was Mycobacterium pseudoshottsii or Mycobacterium marinum. However, additional PCR testing for the insertion sequence 2404 (IS2404) was positive, suggesting that the pathogen was either M. ulcerans or M. ulcerans subsp. shinshuense. Further examination by 16S rRNA sequencing analysis, focusing on nucleotide positions 492, 1247, 1288, and 1449-1451, we finally identified the organism as M. ulcerans subsp. shinshuense. The patient was successfully treated with 12 weeks of clarithromycin and levofloxacin treatment. Mass spectrometry is the latest microbial diagnostic method; however, it cannot be used to identify M. ulcerans subsp. shinshuense. To accurately detect this enigmatic pathogen and uncover its epidemiology and clinical characteristics in Japan, more accumulation of clinical cases with accurate identification of the causative pathogen is essential.

DOI： 10.1016/j.jiac.2023.02.009

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Trends in the Incidence of Japanese Spotted Fever in Japan: A Nationwide, Two-Decade Observational Study from 2001-2020. Reviewed International coauthorship International journal

Yuki Otsuka, Hideharu Hagiya, Shinnosuke Fukushima, Ko Harada, Toshihiro Koyama, Fumio Otsuka

The American journal of tropical medicine and hygiene   108 ( 4 )   701 - 704   2023.2

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The worldwide spread of tick-borne diseases (TBDs) has become a public health concern. Therefore, this study aimed to clarify trends in the incidence of Japanese spotted fever (JSF), one of Japan's most prevalent TBDs. Weekly infectious disease reports were used to calculate the annual incidence rates (AIRs) of JSF. Data were stratified by age and sex, and joinpoint regression analysis was performed to estimate the annual percentage change (APC). AIR and APC were geographically compared among the 47 prefectures. A total of 3,453 JSF cases were observed from 2001 to 2020. The AIR per 100,000 population was 0.03 in 2001, which increased approximately 10-fold to 0.33 in 2020. The average APC (AAPC) during the study period was 12.3% (95% CI: 10.7-13.9). By age group, the incidence of JSF increased more rapidly among the older population: 11.5% (95% CI: 10.1-12.9) in those aged ≥ 65 years and 8.9% (95% CI: 6.4-11.5) in those aged < 50 years. Although the AIR over the past two decades was higher in climatically warm regions located in southwestern Japan and on the Pacific coast, increases in the AAPC were notable in colder regions located in eastern Japan. The incidence of JSF continues to increase in Japan, especially among older populations and in eastern prefectures, where the disease has not been previously diagnosed.

DOI： 10.4269/ajtmh.22-0487

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Prevalence of Inducible Macrolide, Lincosamide, and Streptogramin B (inducible MLSB) Resistance in Clindamycin-Susceptible Staphylococcus aureus at Okayama University Hospital. Reviewed

Lutfun Nahar, Hideharu Hagiya, Takahiro Nada, Koji Iio, Kazuyoshi Gotoh, Osamu Matsushita, Fumio Otsuka

Acta medica Okayama   77 ( 1 )   1 - 9   2023.2

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Inducible resistance to the macrolide, lincosamide, and streptogramin B (iMLSB) antibiotic family is a latent mechanism for antimicrobial resistance in Staphylococcus aureus. We here investigated the frequency and genotypic profiles of iMLSB resistance in clindamycin (CLDM)-susceptible S. aureus isolated in Okayama University Hospital from June 2020 to June 2021. We phenotypically screened the iMLSB resistance via D-zone test and performed PCR testing for the erythromycin ribosomal methylase (erm) genes: ermA and ermC. Among 432 CLDM-susceptible S. aureus isolates, 138 (31.9%) exhibited an iMLSB-resistance phenotype, with methicillinresistant S. aureus isolates (MRSA; 61 isolates: 58.6%) exhibiting higher positivity than methicillin-sensitive S. aureus isolates (MSSA; 77 isolates: 23.5%) (p<0.001). Male patients had a higher frequency of iMLSB resistance than females (OR [95%CI]: 1.8 [1.2-2.8]; p=0.007). Genotypically, ermA predominated in both MSSA (70.1%) and MRSA (86.9%) compared to ermC (14.3% in MSSA and 11.5% in MRSA). A single strain of MRSA possessed both ermA and ermC, while 12 (15.6%) MSSA isolates were negative for both ermA and ermC, suggesting the presence of other genetic mechanisms. Collectively, these results show that approximately 33% of CLDM-susceptible S. aureus isolates at our university hospital exhibited iMLSB resistance, predominantly caused by ermA in both MSSA and MRSA.

DOI： 10.18926/AMO/64355

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不明熱の原因となるカンピロバクター菌血症の臨床的特徴に関する多施設後方研究

大塚 勇輝, 萩谷 英大, 高橋 美砂, 福島 伸乃介, 前田 瑠璃, 砂田 匠彦, 山田 晴士, 岸田 雅之, 藤田 浩二, 大塚 文男

日本病院総合診療医学会雑誌   19 ( 臨増1 )   214 - 214   2023.2

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COVID-19罹患後にME/CFSに移行する症例の臨床的特徴 血清ferritinと内分泌系に注目した検討

山本 幸近, 大塚 勇輝, 徳増 一樹, 萩谷 英大, 砂田 匠彦, 本多 寛之, 中野 靖浩, 櫻田 泰江, 松田 祐依, 長谷川 徹, 長谷川 功, 小比賀 美香子, 植田 圭吾, 片岡 仁美, 大塚 文男

日本病院総合診療医学会雑誌   19 ( 臨増1 )   173 - 173   2023.2

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COVID-19罹患後症状と血清亜鉛濃度の関連

松田 祐依, 徳増 一樹, 大塚 勇輝, 砂田 匠彦, 本多 寛之, 櫻田 泰江, 中野 靖浩, 長谷川 徹, 萩谷 英大, 小比賀 美香子, 植田 圭吾, 片岡 仁美, 大塚 文男

日本病院総合診療医学会雑誌   19 ( 臨増1 )   168 - 168   2023.2

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Trends in Long COVID Symptoms in Japanese Teenage Patients. Reviewed International journal

Yasue Sakurada, Yuki Otsuka, Kazuki Tokumasu, Naruhiko Sunada, Hiroyuki Honda, Yasuhiro Nakano, Yui Matsuda, Toru Hasegawa, Kanako Ochi, Hideharu Hagiya, Keigo Ueda, Hitomi Kataoka, Fumio Otsuka

Medicina (Kaunas, Lithuania)   59 ( 2 )   2023.1

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Background: Since the start of the global pandemic of coronavirus disease 2019 (COVID-19), not only adults but also many children have suffered from it. However, the clinical characteristics of long COVID in children remain unclear. Methods: In this retrospective observational study conducted in a single facility, we reviewed the medical records of all long COVID patients who visited Okayama University Hospital from February 2021 to October 2022, and we compared the clinical characteristics of long COVID in teenagers (11 to 18 years of age) with those in adults. Results: Data for 452 long COVID patients including 54 teenagers (11.9%) were analyzed. Fatigue was the most frequent symptom in teenagers (55.6% of the patients) and also in adults. On the other hand, the percentage of teenagers who complained of headache, which was the second most frequent complaint, was significantly higher than the percentage of adults (35.2% vs. 21.9%, p < 0.05). A comparison of the frequencies of symptoms depending on the viral variant showed that fatigue and headache were predominant symptoms in the Omicron variant phase. Of the 50 teenagers who were enrolled in schools, 28 (56.0%) could not attend school due to long COVID symptoms. The most common symptoms as reasons for absence from school were fatigue (85.7% of the patients), headache (42.9%), and insomnia (32.1%). Conclusions: Attention should be paid to the symptoms of fatigue and headache in teenagers with long COVID.

DOI： 10.3390/medicina59020261

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Tuberculous meningitis Reviewed International journal

Shinnosuke Fukushima, Kazuki Ocho, Koji Fujita, Hideharu Hagiya, Fumio Otsuka

Clinical Case Reports   11 ( 1 )   e6865   2023.1

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Tuberculous meningitis is possibly complicated with multiple cerebral infarctions and basal meningitis, and the mortality and neurological prognosis is reportedly poor. This case suggested that clinicians should consider tuberculous meningitis as a differential diagnosis of patients with disturbed consciousness in an aging country Japan.

DOI： 10.1002/ccr3.6865

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ccr3.6865

Clinical characteristics of Campylobacter bacteremia: a multicenter retrospective study. Reviewed International journal

Yuki Otsuka, Hideharu Hagiya, Misa Takahashi, Shinnosuke Fukushima, Ruri Maeda, Naruhiko Sunada, Haruto Yamada, Masayuki Kishida, Koji Fujita, Fumio Otsuka

Scientific reports   13 ( 1 )   647 - 647   2023.1

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Campylobacter species are the pathogens of the intestinal tract, which infrequently cause bacteremia. To reveal the clinical characteristics of Campylobacter bacteremia, we performed a retrospective, multicenter study. Patients diagnosed with Campylobacter bacteremia in three general hospitals in western Japan between 2011 and 2021 were included in the study. Clinical, microbiological, and prognostic data of the patients were obtained from medical records. We stratified the cases into the gastroenteritis (GE) and fever predominant (FP) types by focusing on the presence of gastrointestinal symptoms. Thirty-nine patients (24 men and 15 women) were included, with a median age of 57 years and bimodal distribution between those in their 20 s and the elderly. The proportion of GE and FP types were 21 (53.8%) and 18 (46.2%), respectively. Comparing these two groups, there was no significant difference in patient backgrounds in terms of sex, age, and underlying diseases. Campylobacter jejuni was exclusively identified in the GE type (19 cases, 90.5%), although other species such as Campylobacter fetus and Campylobacter coli were isolated in the FP type as well. Patients with the FP type underwent intravenous antibiotic therapy more frequently (47.6% vs. 88.9%), and their treatment (median: 5 days vs. 13 days) and hospitalization (median: 7 days vs. 21 days) periods were significantly longer. None of the patients died during the hospitalization. In summary, we found that nearly half of the patients with Campylobacter bacteremia presented with fever as a predominant manifestation without gastroenteritis symptoms.

DOI： 10.1038/s41598-022-27330-4

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Biofilm-associated candidal thrombophlebitis Reviewed International journal

Shinnosuke Fukushima, Koichiro Yamamoto, Yasuhiro Nakano, Hideharu Hagiya, Fumio Otsuka

IDCases   31   e01733 - e01733   2023

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DOI： 10.1016/j.idcr.2023.e01733

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Cryptococcal Meningitis Developing in a Patient with Neurosarcoidosis Reviewed

Shinnosuke Fukushima, Hideharu Hagiya, Yukichika Yamamoto, Kohei Oguni, Kou Hasegawa, Fumio Otsuka

Internal Medicine   62 ( 16 )   2433 - 2435   2023

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

Cryptococcal meningitis is a critical disease that occasionally involves immunosuppressed patients. We herein report a 79-year-old Japanese man who received low-dose prednisolone therapy for neurosarcoidosis and panhypopituitarism. He presented a 10-day history of a fever and altered mental status. The FilmArray® Meningitis/Encephalitis Panel and serum cryptococcal antigen tests were both negative, but the cerebrospinal fluid sample became positive for Cryptococcus neoformans after seven-day incubation. After the diagnosis of cryptococcal meningitis, we successfully treated the patient with a recommended treatment regimen. When an immunocompromised patient presents with a subacute fever accompanying any central nervous symptoms, cryptococcal meningitis should be screened for.

DOI： 10.2169/internalmedicine.0879-22

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Shortage and unequal distribution of infectious disease specialists in Japan: How can we refine the current situation? Reviewed International journal

Hideharu Hagiya

PloS one   18 ( 10 )   e0291677   2023

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BACKGROUND: This study aimed to assess the distribution of board-certified infectious disease (ID) specialists at medical schools and Designated Medical Institutions (DMIs) in Japan. METHODS: Data on the number of board-certified ID specialists was extracted by gender, prefecture, and hospital from the Japanese Association for Infectious Diseases database. The numbers and types of Japanese university hospitals that have a Faculty of Medicine, as well as the DMIs legally determined by the Infectious Diseases Control Law, were collected from the database of the Ministry of Health, Labour, and Welfare of Japan. RESULTS: As of November 2022, there were 1,688 board-certified ID specialists in Japan, with 510 employed at 82 university hospitals. Two medical schools had no ID specialists, and six had only one ID specialist. There was no ID specialists in 14.3% of Class I DMIs and 66.7% of Class II DMIs. Additionally, 14.9% of prefectures had no ID specialists at all in their Class II DMIs. The percentage of female doctors among ID specialists was 12.7%, approximately half of the overall male-to-female ratio of medical doctors in Japan. CONCLUSION: The allocation of Japanese ID specialists to medical schools and legally designated healthcare institutes is inadequate and skewed. Female physicians are expected to play a more active role in this increasing demand.

DOI： 10.1371/journal.pone.0291677

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A randomized controlled trial of teprenone in terms of preventing worsening of COVID-19 infection. Reviewed International journal

Eiki Ichihara, Kou Hasegawa, Kenichiro Kudo, Yasushi Tanimoto, Kazuhiro Nouso, Naohiro Oda, Sho Mitsumune, Haruto Yamada, Ichiro Takata, Hideharu Hagiya, Toshiharu Mitsuhashi, Akihiko Taniguchi, Shinichi Toyooka, Kohei Tsukahara, Toshiyuki Aokage, Hirokazu Tsukahara, Katsuyuki Kiura, Yoshinobu Maeda

PloS one   18 ( 10 )   e0287501   2023

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BACKGROUND: Some COVID-19 patients develop life-threatening disease accompanied by severe pneumonitis. Teprenone induces expression of heat-shock proteins (HSPs) that protect against interstitial pneumonia in preclinical models. We explored whether teprenone prevented worsening of COVID-19 infections. METHODS: This open-label, randomized, pilot phase 2 clinical trial was conducted at five institutions in Japan. We randomized patients hospitalized for COVID-19 with fever to teprenone or no-teprenone groups in a 1:1 ratio. We stratified patients by sex, age < and ≥ 70 years and the existence (or not) of complications (hypertension, diabetes, ischemic heart disease, chronic pulmonary disease and active cancer). No limitation was imposed on other COVID-19 treatments. The primary endpoint was the intubation rate. RESULTS: One hundred patients were included, 51 in the teprenone and 49 in the no- teprenone groups. The intubation rate did not differ significantly between the two groups: 9.8% (5/51) vs. 2.0% (1/49) (sub-hazard ratio [SHR] 4.99, 95% confidence interval [CI]: 0.59-42.1; p = 0.140). The rates of intra-hospital mortality and intensive care unit (ICU) admission did not differ significantly between the two groups: intra-hospital mortality 3.9% (2/51) vs. 4.1% (2/49) (hazard ratio [HR] 0.78, 95%CI: 0.11-5.62; p = 0.809); ICU admission 11.8% (6/51) vs. 6.1% (3/49) (SHR 1.99, 95%CI: 0.51-7.80; p = 0.325). CONCLUSION: Teprenone afforded no clinical benefit. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs061200002 (registered on 20/May/2020).

DOI： 10.1371/journal.pone.0287501

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Characteristics of Sleep Disturbance in Patients with Long COVID: A Retrospective Observational Study in Japan. Reviewed International journal

Naruhiko Sunada, Yasuhiro Nakano, Yuki Otsuka, Kazuki Tokumasu, Hiroyuki Honda, Yasue Sakurada, Yui Matsuda, Toru Hasegawa, Daisuke Omura, Kanako Ochi, Hideharu Hagiya, Keigo Ueda, Hitomi Kataoka, Fumio Otsuka

Journal of clinical medicine   11 ( 24 )   2022.12

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OBJECTIVES: The objective of this study was to determine the clinical and endocrinological features of sleep disturbance in patients with long COVID. METHODS: This study was a single-center retrospective observational study for patients who visited the COVID-19 aftercare outpatient clinic (CAC) established in Okayama University Hospital in Japan during the period from 15 February 2021 to 29 July 2022. The long COVID patients were divided into two groups based on the presence or absence of sleep disturbance, and the clinical and laboratory characteristics of the patients were analyzed. RESULTS: Out of 363 patients with long COVID, after excluding 6 patients, 60 patients (16.5%) (55% males, median age of 38 years) complaining of sleep disturbance were compared with 303 patients (83.5%) (43% males, median age of 40 years) without sleep-related symptoms. Although there were no significant differences in clinical backgrounds and severities of COVID-19 between the two groups by the multivariate analysis, the percentage of long COVID patients with sleep disturbance was significantly increased among patients infected in the Omicron-dominant phase. In addition, the prevalence rate of sleep disturbance in patients when infected in the Omicron phase (24.8%) was two-times higher than that in patients infected in the Delta phase (12.8%). Of note, the percentages of patients with sleep disturbance who also complained of general fatigue, headache, concentration loss, anxiety, low-grade fever, and brain fog symptoms were higher than the percentages of patients without sleep disturbance who had the same complaints. Among the types of sleep disturbance, the percentage of patients who complained of loss of sleep induction (75%) was much higher than the percentage of patients with early-awakening sleep disturbance (6.7%), and many of the patients with mid-awakening types of insomnia had brain fog symptoms. Endocrine examinations revealed that long COVID patients with sleep disturbance had significantly higher levels of plasma adrenocorticotropin and lower levels of serum growth hormone, suggesting the presence of hypothalamic-pituitary stress. CONCLUSION: The prevalence of sleep disturbance has been increasing in long COVID patients infected in the Omicron phase with a certain clinical and endocrine trend.

DOI： 10.3390/jcm11247332

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Clinical Utility of Therapeutic Hyperthermia for Patients With Sepsis Needs Further Investigation. Reviewed International journal

Hideharu Hagiya

Critical care medicine   50 ( 12 )   e811-e812   2022.12

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DOI： 10.1097/CCM.0000000000005646

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Detection of Enterobacter cloacae complex strain with a blaNDM-1-harboring plasmid from an elderly resident at a long-term care facility in Okayama, Japan. Reviewed International journal

Kazuyoshi Gotoh, Hideharu Hagiya, Koji Iio, Haruto Yamada, Osamu Matsushita, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   28 ( 12 )   1697 - 1699   2022.12

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Amidst the global spread of antimicrobial resistance, New Delhi metallo-β-lactamase (NDM)-type carbapenemase-producing Enterobacterales (CPE) remain uncommon in Japan, and the detection of such highly drug-resistant organisms is limited to inbound cases. There is little evidence regarding the prevalence of NDM β-lactamase gene (blaNDM)-harboring CPE in the domestic community, especially in the provincial cities of Japan. Herein, we report the isolation of a blaNDM-1-harboring plasmid in Enterobacter cloacae complex strain isolated from an elderly woman without a history of traveling abroad who had resided in a long-term care facility in Okayama, Japan. The multidrug-resistant blaNDM-harboring CPE isolate was detected in a stool sample of the patient during routine screening at admission. We performed whole-genome sequencing analysis of the isolate using MiSeq (Illumina) and MinION (Oxford Nanopore Technologies) platforms. The isolate was identified as sequence type 171, which has predominantly been reported in the United States and China. The blaNDM-1 gene was encoded on the 46,161 bp IncX3 plasmid, with sequence similarity to plasmids of similar size isolated from individuals in China. Collectively, the genomic data suggest that an imported CPE isolate may have spread among healthy individuals in the regional area of Japan.

DOI： 10.1016/j.jiac.2022.08.019

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Rhinogenic optic neuropathy with hemianopia caused by ethmoidal sinus mucocele. Reviewed International journal

Kosuke Oka, Wataru Ando, Hideharu Hagiya, Takaya Higaki, Fumio Otsuka

Clinical case reports   10 ( 12 )   e6696   2022.12

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A patient complained of acute right vision loss and headache. A computed tomography scan revealed ethmoidal sinus mucocele in the right ethmoid sinus that was compressing the optic nerve and emergency endoscopic sinus surgery was performed.

DOI： 10.1002/ccr3.6696

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Early-stage antibody kinetics after the third dose of BNT162b2 mRNA COVID-19 vaccination measured by a point-of-care fingertip whole blood testing Reviewed International journal

Hideharu Hagiya, Yasuhiro Nakano, Masanori Furukawa, Naruhiko Sunada, Toru Hasegawa, Yasue Sakurada, Kou Hasegawa, Koichiro Yamamoto, Hiroko Ogawa, Takafumi Obara, Kouhei Ageta, Naomi Matsumoto, Rumi Matsuo, Tomoka Kadowaki, Akihito Higashikage, Takao Hikita, Takashi Yorifuji, Shinichi Toyooka, Yoshinobu Maeda, Yoshinori Yokokura, Fumio Otsuka, Masanori Nakayama

Scientific Reports   12 ( 1 )   20628 - 20628   2022.11

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Amid the Coronavirus Disease 2019 pandemic, we aimed to demonstrate the accuracy of the fingertip whole blood sampling test (FWT) in measuring the antibody titer and uncovering its dynamics shortly after booster vaccination. Mokobio SARS-CoV-2 IgM &amp; IgG Quantum Dot immunoassay (Mokobio Biotechnology R&amp;D Center Inc., MD, USA) was used as a point-of-care FWT in 226 health care workers (HCWs) who had received two doses of the BNT162b2 mRNA vaccine (Pfizer-BioNTech) at least 8 months prior. Each participant tested their antibody titers before and after the third-dose booster up to 14-days. The effect of the booster was observed as early as the fourth day after vaccination, which exceeded the detection limit (&gt; 30,000 U/mL) by 2.3% on the fifth day, 12.2% on the sixth day, and 22.5% after the seventh day. Significant positive correlations were observed between the pre- and post-vaccination (the seventh and eighth days) antibody titers (correlation coefficient, 0.405; p &lt; 0.001). FWT is useful for examining antibody titers as a point-of-care test. Rapid response of antibody titer started as early as the fourth day post-vaccination, while the presence of weak responders to BNT162b2 vaccine was indicated.

DOI： 10.1038/s41598-022-24464-3

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Are Prophylactic Systemic Antibiotics Required in Patients with Cataract Surgery at Local Anesthesia? Reviewed International journal

Toshihiko Matsuo, Masahiro Iguchi, Noriyasu Morisato, Tatsuya Murasako, Hideharu Hagiya

International journal of environmental research and public health   19 ( 23 )   2022.11

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The reduced use of antimicrobial drugs has been recommended worldwide, according to the global action for antimicrobial resistance published in 2015 by the World Health Organization. In this study, we retrospectively reviewed the incidence of surgical site infection in consecutive patients with cataract surgeries at a single hospital in the 6-year process when prophylactic systemic antibiotics were reduced in a step-by-step manner. The entire study period from 2016 to 2022 was divided into five stages, based on the use of systemic antibiotics. In stage 1 with 649 cataract surgeries, an intravenous drip infusion of cefazolin 1 g was given at surgery, followed by oral cefdinir 100 mg in the evening on surgery day and three times for two postoperative days. In stage 2 with 541 cataract surgeries, oral cefdinir 100 mg was given in the late morning before surgery, in the evening, and three times (300 mg in total) for two postoperative days. In stage 3 with 103 cataract surgeries, oral levofloxacin 500 mg was given in the late morning before surgery and once in the morning for two postoperative days. In stage 4 with 545 cataract surgeries, oral levofloxacin 500 mg was given only in the late morning before surgery. In stage 5 with 311 cataract surgeries, no systemic antibiotics were given. As common procedures in all stages, moxifloxacin eye drops were given four times daily as topical antibiotics in the 3 days before surgery and about 2 weeks after surgery. At surgery, the ocular surface was frequently irrigated with saline-diluted povidone iodine at 0.5% working concentration. No postoperative infection was recorded in any stage. This study showed neither harm nor risk in reduced use and, consequently, no use of prophylactic systemic antibiotics in cataract surgery as far as local precautionary measures were secured.

DOI： 10.3390/ijerph192315796

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High frequency of extended-spectrum beta-lactamase-producing Enterobacteriaceae carriers at a Japanese long-term care hospital. Reviewed International journal

Hideharu Hagiya, Yuji Onishi, Natsumi Shinohara, Mayumi Tokuyasu, Aki Imanishi, Shinnosuke Fukushima, Lutfun Nahar, Koji Iio, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   28 ( 11 )   1578 - 1581   2022.11

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INTRODUCTION: Long-term care hospitals (LTCHs) are at a high risk for the inflow and spread of antimicrobial resistance (AMR) pathogens. However, owing to limited laboratory resources, little is known about the extent to which AMR organisms are endemic. METHODS: We performed active surveillance for carbapenem-resistant Enterobacteriaceae (CRE) and extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-E) in newly admitted patients at Marugame Medical Center, a nearly 200-bedded LTCH located in Kagawa, Japan. From August to December 2021, we tested stool samples from patients wearing diapers and confirmed the genetic variants using specific PCR assays. We also collected clinical variables and compared them between AMR carriers and non-carriers. RESULTS: Stool samples were collected from 75 patients, with a median age of 84 years. CRE strain was not detected, but 37 strains of ESBL-E were isolated from 32 patients (42.7%). During the study period, 4.9% of in-hospital patients (37 per 756 patients) were identified to be ESBL-E carriers in the routine microbiological processing, suggesting that active surveillance detected approximately 9-fold more ESBL-E carriers. The blaCTX-M-9 group was the most common (38.5%), followed by the blaTEM (26.9%). The clinical backgrounds of the ESBL-E non-carriers and carriers were not significantly different. CONCLUSION: Our active screening demonstrated that nearly half of the patients hospitalized or transferred to a Japanese LTCH were colonized with ESBL-E. We highlight the enforcement of universal basic infection prevention techniques at LTCHs where patients carrying AMR pathogens gather.

DOI： 10.1016/j.jiac.2022.07.014

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RSウイルス感染症の全国サーベイランスとGoogle Trendsの相関性に関する検討

宇田 和宏, 萩谷 英大, 頼藤 貴志, 小山 敏広, 茂原 研司, 津下 充, 八代 将登, 本田 知之, 塚原 宏一

日本小児感染症学会総会・学術集会プログラム・抄録集   54回   194 - 194   2022.11

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Cefepime-induced neurotoxicity: systematic review. Reviewed International journal

Gozun Maan, Koichi Keitoku, Nobuhiko Kimura, Haruki Sawada, Andrew Pham, Jihun Yeo, Hideharu Hagiya, Yoshito Nishimura

The Journal of antimicrobial chemotherapy   77 ( 11 )   2908 - 2921   2022.10

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BACKGROUND: Cefepime-induced neurotoxicity (CIN) has been well acknowledged among clinicians, although there are no clear diagnostic criteria or specific laboratory testing to help with its diagnosis. We aimed to summarize the existing evidence regarding CIN and provide future agendas for research. METHODS: Following the PRISMA Extension for Scoping Reviews, we searched MEDLINE and Embase for all peer-reviewed articles using keywords including 'cefepime', 'neurotoxicity', 'encephalopathy' and 'seizure', from their inception to 20 January 2022. RESULTS: We included 92 articles, including 23 observational studies and 69 cases from case reports and case series, in the systematic review. Among 119 patients with CIN, 23.5% were in the ICU at the time of diagnosis and nearly 90% of the cases showed renal dysfunction.Cefepime overdoses were described in 41%. The median latency period of developing CIN from cefepime initiation was 4 days, and about 12% developed CIN during empirical treatment. CIN patients commonly manifested altered mental status (93%), myoclonus (37%) and non-convulsive seizure epilepticus (28%). A serum cefepime trough level of >20 mg/L would put patients at risk for CIN. CIN-related symptoms were ameliorated in 97.5% by dose reduction or discontinuation of cefepime, with median time to improvement of 3 days. No CIN-associated deaths were reported. CONCLUSIONS: This systematic review summarizes the current evidence and characteristics of CIN. In the current situation where there are no CIN diagnostic criteria and the drug monitoring platform is not routinely available, candidates for cefepime should be carefully selected. Also, based on these findings, it needs to be appropriately dosed to avoid the development of CIN.

DOI： 10.1093/jac/dkac271

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Antimicrobials in the Hospital are Unevenly Discontinued on Weekdays. Reviewed

Hideharu Hagiya, Mika Uno, Tsukasa Higashionna, Hiroyuki Honda, Fumio Otsuka

Internal medicine (Tokyo, Japan)   62 ( 12 )   1739 - 1742   2022.10

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Objective Amid the global spread of antimicrobial resistance, antimicrobial stewardship should be further promoted in the clinical setting. Our previous study suggested an intra-week disproportion of discontinuation of broad-spectrum antibiotics. We therefore explored the generalization of this prescription trend by investigating the use of all intravenous antibiotics. Methods A retrospective, observational study. Patients Between January 1, 2018, and December 31, 2020, we collected data on the initiation and discontinuation of intravenous antimicrobials on each day of the week and on days after holidays at Okayama University Hospital, Japan. We compared the monthly antimicrobial prescription initiation and discontinuation using the Kruskal-Wallis test and Mann-Whitney U-test with Bonferroni correction as a post-hoc procedure. Results Data from 15,293 hospitalized cases were analyzed. The initiation of antimicrobials differed slightly among days of the week, although this trend was clinically insignificant. Compared with the initiations, antimicrobial discontinuations were disproportionately biased among the weekdays, tending to occur on Mondays (p <0.001) about twice as often as on other days. Similarly, antimicrobials were unevenly discontinued on the day after holidays compared to other days (p <0.001), with an approximately 2-fold difference. The use of antimicrobials in the hospital was thus unequally terminated on weekdays. Conclusion To further promote antimicrobial stewardship, clinicians should be aware of the influence of behavioral, environmental, and social factors on antimicrobial prescription, which is seemingly beyond medical indications.

DOI： 10.2169/internalmedicine.0707-22

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Prevalence of medical factors related to aging among older car drivers: a multicenter, cross-sectional, descriptive study. Reviewed International journal

Hideharu Hagiya, Ryosuke Takase, Hiroyuki Honda, Yasuhiro Nakano, Yuki Otsuka, Hitomi Kataoka, Mika Uno, Keigo Ueda, Misa Takahashi, Hiroko Ogawa, Yoshihisa Hanayama, Fumio Otsuka

BMC geriatrics   22 ( 1 )   792 - 792   2022.10

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AIM: An increasing number of older adults in Japan are at an increased risk of road traffic crashes. This study aimed to investigate the prevalence of potential underlying medical factors that increase the risk of road traffic crashes among older people. METHODS: This cross-sectional observational study was conducted in 11 medical institutions in Japan using self-administered questionnaires and physical examination from January to May 2021. The background and social data, data on the use of nursing care insurance, and clinical data suggestive of polypharmacy, sarcopenia, cognitive impairment, and frailty/oral frailty were obtained. The prevalence of these factors was compared between everyday and occasional drivers. RESULTS: Data of 127 patients were collected; their median (interquartile range) age was 73 (70-78) years. Of the total participants, 82 were men (64.6%) and 45 were women (35.4%). There were 77 everyday drivers and 50 occasional drivers. Of these, 121 (95.3%) had not applied for nursing care insurance, but the numbers of those who required help 1 and 2 were 1 (0.8%) and 3 (2.4%), respectively. Prevalence of medical factors was as follows: polypharmacy, 27.6%; sarcopenia, 8.7%; dementia, 16.4%; frailty, 15.0%; and oral frailty, 54.3%; it was not significantly different between every day and occasional drivers. Intention to return the car license was significantly higher among the occasional drivers (2.6% vs. 14.0%; odds ratio: 6.7, 95% confidence interval: 1.2-70.6, p = 0.024). CONCLUSION: We uncovered the prevalence of medical factors that can be associated with road traffic crashes among Japanese older people aged ≥ 65 years in our community.

DOI： 10.1186/s12877-022-03490-w

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Transitional Changes in Fatigue-Related Symptoms Due to Long COVID: A Single-Center Retrospective Observational Study in Japan. Reviewed International journal

Yasuhiro Nakano, Yuki Otsuka, Hiroyuki Honda, Naruhiko Sunada, Kazuki Tokumasu, Yasue Sakurada, Yui Matsuda, Toru Hasegawa, Kanako Ochi, Hideharu Hagiya, Hitomi Kataoka, Keigo Ueda, Fumio Otsuka

Medicina (Kaunas, Lithuania)   58 ( 10 )   2022.10

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Background and Objectives: Changes in post COVID-19 condition (PCC) characteristics caused by viral variants have yet to be clarified. We aimed to characterize the differences between clinical backgrounds and manifestations in long COVID patients who were infected with the Delta variant and those who were infected with the Omicron variants. Materials and Methods: This study was a single-center retrospective observational study for patients who visited our COVID-19 aftercare outpatient clinic (CAC) established in Okayama University Hospital (Japan) during the period from 15 February 2021 to 15 July 2022. We classified the onset of COVID-19 in the patients into three groups, the preceding, Delta-dominant, and Omicron-dominant periods, based on the prevalent periods of the variants in our prefecture. Results: In a total of 353 patients, after excluding 8 patients, 110, 130, and 113 patients were classified into the preceding, Delta-dominant, and Omicron-dominant periods, respectively. Patients infected in the Omicron-dominant period had significantly fewer hospitalizations, milder illnesses, more vaccinations and earlier visit to the CAC than did patients infected in the Delta-dominant period. Patients infected in the Omicron-dominant period had significantly lower frequencies of dysosmia (12% vs. 45%, ** p &lt; 0.01), dysgeusia (14% vs. 40%, ** p &lt; 0.01) and hair loss (7% vs. 28%, ** p &lt; 0.01) but had higher frequencies of fatigue (65% vs. 50%, * p &lt; 0.05), insomnia (26% vs. 13%, * p &lt; 0.05) and cough (20% vs. 7%, ** p &lt; 0.01) than did patients infected in the Delta-dominant period. Conclusions: The transitional changes in long COVID symptoms caused by the two variants were characterized.

DOI： 10.3390/medicina58101393

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Candida dubliniensis fungemia in a patient with severe COVID-19: A case report. Reviewed International journal

Ayaka Kakehi, Hideharu Hagiya, Koji Iio, Yasuhiro Nakano, Hiromi Ihoriya, Yuki Taira, Kenta Nakamoto, Kou Hasegawa, Akihito Higashikage, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   28 ( 10 )   1433 - 1435   2022.10

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Candida dubliniensis phenotypically mimics Candida albicans in its microbiological features; thus, its clinical characteristics have yet to be fully elucidated. Here we report the case of a 68-year-old Japanese man who developed C. dubliniensis fungemia during treatment for severe coronavirus disease 2019 (COVID-19). The patient was intubated and received a combination of immunosuppressants, including high-dose methylprednisolone and two doses of tocilizumab, as well as remdesivir, intravenous heparin, and ceftriaxone. A blood culture on admission day 11 revealed Candida species, which was confirmed as C. dubliniensis by mass spectrometry. An additional sequencing analysis of the 26S rDNA and ITS regions confirmed that the organism was 100% identical to the reference strain of C. dubliniensis (ATCC MYA-646). Considering the simultaneous isolation of C. dubliniensis from a sputum sample, the lower respiratory tract could be an entry point for candidemia. Although treatment with micafungin successfully eradicated the C. dubliniensis fungemia, the patient died of COVID-19 progression. In this case, aggressive immunosuppressive therapy could have caused the C. dubliniensis fungemia. Due to insufficient clinical reports on C. dubliniensis infection based on definitive diagnosis, the whole picture of the cryptic organism is still unknown. Further accumulation of clinical and microbiological data of the pathogen is needed to elucidate their clinical significance.

DOI： 10.1016/j.jiac.2022.07.007

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Clinical and microbiological characteristics of polymicrobial bacteremia: a retrospective, multicenter study. Reviewed International journal

Shinnosuke Fukushima, Hideharu Hagiya, Koji Fujita, Shinya Kamiyama, Haruto Yamada, Masayuki Kishida, Fumio Otsuka

Infection   50 ( 5 )   1233 - 1242   2022.10

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PURPOSE: To clarify the clinical and microbial characteristics of polymicrobial bacteremia (PMB) to contribute to improvements in clinical diagnosis and effective early treatment. METHODS: This retrospective multicenter study used data from three acute-care hospitals in Okayama Prefecture, Japan, collected between January 2014 and March 2019. We reviewed the demographics, comorbidities, organisms isolated, infectious focus, and 30-day mortality of patients with PMB. RESULTS: Of the 7233 positive blood cultures, 808 (11.2%) were positive for more than one organism. Of the patients with bacteremia, 507 (7.0%) had PMB, of whom 65.3% were male. Infectious foci were identified in 78.3% of the cases, of which intra-abdominal infections accounted for 47.1%. A combination of Gram-positive cocci (GPC) (chain form) and Gram-negative rods (GNR) accounted for 32.9% of the cases, and GPC/GNR and GNR/GNR patterns were significantly associated with intra-abdominal infections. The 30-day mortality rate of patients with PMB was 18.1%, with a median of 7.5 days from diagnosis to death. The mortality in patients with an infectious focus identified was significantly lower than that in patients with an unknown focus (16.3% vs. 24.5%; p = 0.031). CONCLUSIONS: Intra-abdominal infections were the most common source of PMB, and were strongly associated with a Gram-staining combination pattern of GPC (chain form)/GNR. PMB cases with an unknown focus had a poorer prognosis, highlighting the importance of early diagnosis and appropriate treatment.

DOI： 10.1007/s15010-022-01799-7

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Kikuchi-Fujimoto disease manifesting bilateral lymphadenopathy. Reviewed International journal

Akihiro Kawatsuki, Kosuke Oka, Hideharu Hagiya, Fumio Otsuka

Clinical case reports   10 ( 10 )   e6494   2022.10

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Physicians should keep in mind that Kikuchi-Fujimoto disease can show bilateral lymphadenopathy like the present case.

DOI： 10.1002/ccr3.6494

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COVID-19罹患後症状における内分泌機能に関する検討

砂田 匠彦, 本多 寛之, 中野 靖浩, 山本 絋一郎, 徳増 一樹, 櫻田 泰江, 松田 祐依, 長谷川 徹, 大塚 勇輝, 小比賀 美香子, 花山 宜久, 萩谷 英大, 植田 圭吾, 片岡 仁美, 大塚 文男

日本内分泌学会雑誌   98 ( 2 )   628 - 628   2022.10

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経過中にインスリノーマを認めた高齢2型糖尿病の1例

長岡 寛和, 本多 寛之, 斎藤 光希, 田中 秀一, 山本 紘一郎, 石田 智治, 長谷川 功, 萩谷 英大, 大塚 文男

日本内分泌学会雑誌   98 ( 2 )   620 - 620   2022.10

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心室期外収縮を契機に判明した反応性低血糖の1例

本多 寛之, 田中 秀一, 中野 靖弘, 長谷川 功, 萩谷 英大, 小比賀 美香子, 大塚 文男

日本内分泌学会雑誌   98 ( 2 )   619 - 619   2022.10

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心室期外収縮を契機に判明した反応性低血糖の1例

本多 寛之, 田中 秀一, 中野 靖弘, 長谷川 功, 萩谷 英大, 小比賀 美香子, 大塚 文男

日本内分泌学会雑誌   98 ( 2 )   619 - 619   2022.10

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経過中にインスリノーマを認めた高齢2型糖尿病の1例

長岡 寛和, 本多 寛之, 斎藤 光希, 田中 秀一, 山本 紘一郎, 石田 智治, 長谷川 功, 萩谷 英大, 大塚 文男

日本内分泌学会雑誌   98 ( 2 )   620 - 620   2022.10

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Splenomegaly in silent endocarditis Reviewed

T Ishida, H Hagiya, Y Yamamoto, K Oguni, F Otsuka

QJM: An International Journal of Medicine   115 ( 9 )   615 - 616   2022.9

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DOI： 10.1093/qjmed/hcac150

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Impact of the cervical cancer awareness months on public interest in Japan: A Google Trends analysis, 2012-2021. Reviewed International journal

Hideharu Hagiya, Toshihiro Koyama, Fumio Otsuka

Scientific reports   12 ( 1 )   15391 - 15391   2022.9

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The immunization and screening rates for human papillomavirus in Japan are lower than those in other countries. We aimed to evaluate the impact of cervical cancer awareness months on public attention using Google Trends analysis. Between 2012 and 2021, we analyzed the trends in relative search volumes (RSVs) for "Shikyuu-keigan" (cervical cancer in English) in Japan, during the cervical cancer awareness month (CCAM) in January and cervical cancer prevention awareness enhancement month (CCPAEM) in November. We performed a joinpoint regression analysis to identify a statistically significant trend change point. Additionally, we compared the mean RSVs of each awareness month with the rest of the year. Significant trend change points were observed, but none were found in CCAM and CCPAEM periods. Comparison of mean RSVs among CCAM, CCPAEM, and the rest of the months did not suggest any significant increases in RSVs during these awareness periods. In conclusion, CAM and CCPAEM did not raise public interest in cervical cancer in Japan. Although the results are based on internet users, the findings might suggest a need to develop a more effective and attractive approach to achieve the 90-70-90 targets of cervical cancer prevention by 2030.

DOI： 10.1038/s41598-022-19798-x

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Examining the association between vaccine reactogenicity and antibody titer dynamics after the third dose of BNT162b2 vaccine using a mixed-effects model Reviewed International journal

Naomi Matsumoto, Hideharu Hagiya, Masanori Nakayama, Masanori Furukawa, Toshiharu Mitsuhashi, Soshi Takao, Fumio Otsuka, Takashi Yorifuji

Journal of Infection and Chemotherapy   29 ( 1 )   39 - 42   2022.9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

BACKGROUND: To mitigate the COVID-19 pandemic, many countries have recommended the use of booster vaccinations. The relationship between the degree of adverse vaccine reactions and elevated antibody titers is of interest; however, no studies have investigated the temporal changes in antibody titers based on repeated measurements after a third dose of the BNT162b2 vaccine. METHODS: This prospective longitudinal cohort study was conducted with 62 healthcare workers who received a third dose of the BNT162b2 at Okayama University Hospital, Japan. Venous blood draw and fingertip whole blood test sample collection were conducted at the early (3-13 days) and 1-month time points; only FWT sample collection was conducted at the 2-month time point. Information on adverse reactions within 1 week after vaccination was also obtained. The association between fever of 37.5 °C or higher and antibody titers after the third dose of BNT162b2 was examined using a mixed-effects model and Poisson regression with robust variance. RESULTS: A trend toward higher antibody titers in the early period after vaccination was observed in the febrile individuals, but the differences were not significant at 1 and 2 months post-vaccination (the partial regression coefficient for fever was 8094.3 [-1910.2, 18,098.8] at 1 month after vaccination, and 1764.1 [-4133.9, 7662.1] at 2 months after vaccination in the adjusted models). CONCLUSION: The findings suggest that the presence of fever after the third vaccine does not predict a sustained elevation in serum antibody titers.

DOI： 10.1016/j.jiac.2022.09.012

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[Central Nervous System and Psychiatric Complications in Long Coronavirus Disease 2019].

Hideharu Hagiya, Fumio Otsuka

No shinkei geka. Neurological surgery   50 ( 5 )   1071 - 1077   2022.9

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Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)has prevailed worldwide since early 2020 and has caused the global coronavirus disease 2019(COVID-19)pandemic. A considerable number of patients suffer from various sequela after SARS-CoV-2 infection, which is known as post COVID-19 condition(PCC). Amid the COVID-19 pandemic, we opened a COVID-19 aftercare clinic in February 2021 in Okayama University Hospital, where we specifically consult PCC patients. While examining such patients, three Cs are essential: complexity, continuity, and collaboration. Neurological and psychiatric manifestations are particularly important from the wide range of PCC symptoms. Indeed, a recent meta-analysis demonstrated that PCC patients suffer from brain fog(32%), memory loss(27%), attention disorder(22%), dyssomnia(31%), anxiety(23%), and depression(12%). The pathophysiology and treatment strategies for these conditions are yet to be developed, and further research is required. We have corroborated that endocrinological impairments may underlie the onset and deterioration of PCC. Through our continuous consultation at the COVID-19 aftercare clinic, we intend to conduct research on the pathophysiology of and treatment strategies for PCC.

DOI： 10.11477/mf.1436204667

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01228&link_issn=&doc_id=20220928260020&doc_link_id=10.11477%2Fmf.1436204667&url=https%3A%2F%2Fdoi.org%2F10.11477%2Fmf.1436204667&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

Gap between self-evaluation and actual hand hygiene compliance among health-care workers. Reviewed International journal

Hideharu Hagiya, Ryosuke Takase, Yosuke Sazumi, Yoshito Nishimura, Hiroyuki Honda, Fumio Otsuka

Journal of infection prevention   23 ( 5 )   239 - 242   2022.9

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Hand hygiene (HH) compliance among health-care workers has not satisfactorily improved despite multiple educative approaches. Between October 2019 and February 2020, we performed a self-evaluation test and a direct observation for the compliance of the 5 Moments for Hand Hygiene program advocated by the World Health Organization at two Japanese hospitals. Average percentages of self-evaluated HH compliance were as follows: (i) 76.9% for "Before touching a patient," (ii) 85.8% for "Before clean/aseptic procedures," (iii) 95.9% for "After body fluid exposure/risk," (iv) 84.0% for "After touching a patient," and (v) 69.2% for "After touching patient surroundings." On the other hand, actual HH compliance was 11.7% for "Before touching a patient" and 18.0% for "After touching a patient or patient surroundings." The present study demonstrated a big gap between self-evaluation and actual HH compliance among nurses working at hospitals, indicating the need of further providing the education in infection prevention.

DOI： 10.1177/17571774221094160

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Tuberculous aortic aneurysm developed with miliary tuberculosis. Reviewed International journal

S Tanaka, H Hagiya, F Otsuka

QJM : monthly journal of the Association of Physicians   115 ( 8 )   543 - 544   2022.8

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DOI： 10.1093/qjmed/hcac142

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A Wolff-Parkinson-White syndrome revealed by the event of heat stroke. Reviewed International journal

Shuichi Tanaka, Hideharu Hagiya, Fumio Otsuka

QJM : monthly journal of the Association of Physicians   115 ( 11 )   760 - 761   2022.8

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DOI： 10.1093/qjmed/hcac189

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Correlation between national surveillance and search engine query data on respiratory syncytial virus infections in Japan. Reviewed International journal

Kazuhiro Uda, Hideharu Hagiya, Takashi Yorifuji, Toshihiro Koyama, Mitsuru Tsuge, Masato Yashiro, Hirokazu Tsukahara

BMC public health   22 ( 1 )   1517 - 1517   2022.8

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BACKGROUND: The respiratory syncytial virus (RSV) disease burden is significant, especially in infants and children with an underlying disease. Prophylaxis with palivizumab is recommended for these high-risk groups. Early recognition of a RSV epidemic is important for timely administration of palivizumab. We herein aimed to assess the correlation between national surveillance and Google Trends data pertaining to RSV infections in Japan. METHODS: The present, retrospective survey was performed between January 1, 2018 and November 14, 2021 and evaluated the correlation between national surveillance data and Google Trends data. Joinpoint regression was used to identify the points at which changes in trends occurred. RESULTS: A strong correlation was observed every study year (2018 [r = 0.87, p < 0.01], 2019 [r = 0.83, p < 0.01], 2020 [r = 0.83, p < 0.01], and 2021 [r = 0.96, p < 0.01]). The change-points in the Google Trends data indicating the start of the RSV epidemic were observed earlier than by sentinel surveillance in 2018 and 2021 and simultaneously with sentinel surveillance in 2019. No epidemic surge was observed in either the Google Trends or the surveillance data from 2020. CONCLUSIONS: Our data suggested that Google Trends has the potential to enable the early identification of RSV epidemics. In countries without a national surveillance system, Google Trends may serve as an alternative early warning system.

DOI： 10.1186/s12889-022-13899-y

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Postprandial Reactive Hypoglycemia Detected with Premature Ventricular Contraction. Reviewed International journal

Hiroyuki Honda, Shuichi Tanaka, Hideharu Hagiya, Fumio Otsuka

QJM : monthly journal of the Association of Physicians   115 ( 10 )   675 - 676   2022.7

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DOI： 10.1093/qjmed/hcac167

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Right-sided infective endocarditis with odontogenic infections. Reviewed International journal

Shinnosuke Fukushima, Koji Fujita, Hideharu Hagiya, Fumio Otsuka

QJM : monthly journal of the Association of Physicians   115 ( 11 )   753 - 753   2022.7

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DOI： 10.1093/qjmed/hcac172

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Mediastinal Abscess Induced by Group B Streptococcus. Reviewed

Kenta Nakamoto, Hideharu Hagiya, Ruiko Hayashi, Fumio Otsuka

Internal medicine (Tokyo, Japan)   2022.7

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DOI： 10.2169/internalmedicine.9498-22

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Prevalence of psychological distress on public health officials amid COVID-19 pandemic. Reviewed International journal

Yoshito Nishimura, Tomoko Miyoshi, Hideharu Hagiya, Fumio Otsuka

Asian journal of psychiatry   73   103160 - 103160   2022.7

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OBJECTIVES: While the coronavirus disease 2019 (COVID-19) pandemic has led to increased burnout among frontline healthcare workers (HCWs), little research has been done regarding the potential psychological burden among public health officials who have worked tirelessly to tackle the pandemic from an administrative perspective. This study aimed to determine the prevalence of burnout, depression, and job-related stress in Japanese public health officers amid the COVID-19 pandemic. METHODS: We conducted an anonymous, self-administered web-based cross-sectional survey including basic demographics, work-related questions, the Maslach Burnout Inventory, Patient Health Questionnaire-9, Utrecht Work Engagement Scale-3, and Brief Job Stress Questionnaire. 100 public health officers working in the public health centers (PHCs) in Okayama, Japan, answered the survey in December 2021 when the 5th surge in the number of COVID-19 was over. RESULTS: The prevalence of burnout, depression, and job-related stress was 27%, 43%, and 62%, respectively. The multivariate logistic analysis demonstrated that females, public health nurses, and those who suffered from a lack of support from their workplaces were significantly associated with psychological distress. CONCLUSIONS: While we tend to focus on mitigation plans to help alleviate burnout of frontline HCWs, more focus is needed to help public health officers, and public health nurses, in particular, to alleviate their psychological distress and job-related stress to prevent further staff shortages and secure sustainable health systems.

DOI： 10.1016/j.ajp.2022.103160

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Vancomycin MIC creep progresses in methicillin-resistant Staphylococcus aureus despite the national antimicrobial stewardship campaign: Single facility data in Japan. Reviewed International journal

Takumi Fujimori, Hideharu Hagiya, Koji Iio, Tsukasa Higashionna, Ayaka Kakehi, Mami Okura, Hiroshi Minabe, Yukika Yokoyama, Fumio Otsuka, Akihito Higashikage

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   28 ( 7 )   918 - 922   2022.7

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BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of nosocomial and community infections, and vancomycin (VCM) is widely recommended as a first-line therapeutic drug. Minimum inhibitory concentrations (MICs) of VCM ≤2 μg/mL are defined as susceptible, but increases in these levels, known as "VCM MIC creep" have been reported. The aim of this study was to investigate VCM MIC creep during the promotion of a national antimicrobial stewardship campaign. METHODS: We collected data from 2013 to 2020 on S. aureus isolated at the clinical microbiology laboratory at Okayama University Hospital, Japan. We calculated the annual proportions of MRSA isolation rates by MIC levels for nosocomial and community samples and estimated annual percentage changes in the antimicrobial use density of the VCM. RESULTS: Of the 1,716 MRSA isolates, no strains showed intermediate or resistant ranges of VCM MIC levels. By 2020, the proportion of MRSA with an MIC of ≤0.5 μg/mL decreased to 35.4%, while that with an MIC of 1 μg/mL increased to 64.1% over time. The annual percentage changes of the VCM antimicrobial use density significantly increased without any trend change point (average 8.1%, p = 0.035). There was no clear correlation between the VCM AUD and annual proportion of nosocomial MRSA with MIC 1 μg/mL (correlation coefficient 0.48; p value = 0.24). CONCLUSION: We demonstrated a deteriorating situation of VCM MIC creep among MRSA strains isolated at our university hospital during the national antimicrobial stewardship campaign.

DOI： 10.1016/j.jiac.2022.03.017

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Persistent methicillin-resistant Staphylococcus aureus bacteremia in an adult patient with Netherton's syndrome: A case report. Reviewed International journal

Misa Takahashi, Hideharu Hagiya, Shuichi Tanaka, Koichiro Yamamoto, Hiroyuki Honda, Kou Hasegawa, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   28 ( 7 )   978 - 981   2022.7

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Netherton's syndrome, a rare congenital disorder, is clinically characterized by chronic dermatologic disorders such as ichthyosiform erythroderma and ichthyosis linearis circumflexa. Curable treatment is yet to be established, and corticosteroid ointment is required to maintain good dermatological condition. Because of the permanent skin barrier impairment, patients with Netherton's syndrome are considered to be vulnerable to cutaneous infections. However, its clinical characteristics are yet to be elucidated due to the limited number of reported cases. Herein, we describe the clinical course of a patient who developed persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. A 19-year-old Japanese woman who had been diagnosed with Netherton's syndrome in her infancy and had been applying topical corticosteroid agents all over her body since her then, was referred to our hospital because of persistent MRSA bacteremia and secondary adrenal insufficiency. The patient was diagnosed with a central line-associated bloodstream infection and was appropriately treated with antibiotics and corticosteroid therapies. We assume that the damaged skin barrier due to the congenital dermatological disorder causes a disruption in the normal bacterial flora of the skin, leading to the invasion of harmful bacteria, such as S. aureus. In addition, internal (humoral immunodeficiency by decreased antibody against bacterial polysaccharide antigens) and external (prolonged and systemic use of corticosteroid ointment) factors bring about an immunodeficiency state in such patients. We highlight that in the absence of radical treatment, clinicians need to recognize that patients with Netherton's syndrome are vulnerable to bacterial infections owing to the mixture of immunosuppressive factors.

DOI： 10.1016/j.jiac.2022.02.021

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Poor vaccine responsiveness towards third-dose mRNA vaccine of COVID-19 in Japanese older people Reviewed International journal

Hideharu Hagiya, Takao Hikita, Tomohiro Habu, Masaki Asada, Takashi Yorifuji, Shinichi Toyooka, Fumio Otsuka, Masanori Nakayama

Journal of Infection   85 ( 4 )   436 - 480   2022.7

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.jinf.2022.07.007

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Comparison of extraction-based and elution-based polymerase chain reaction testing, and automated and rapid antigen testing for the diagnosis of severe acute respiratory syndrome coronavirus 2. Reviewed International journal

Nori Yoshioka, Matsuo Deguchi, Hideharu Hagiya, Masanori Kagita, Hiroko Tsukamoto, Miyuki Takao, Hisao Yoshida, Shigeto Hamaguchi, Ikuhiro Maeda, Yoh Hidaka, Kazunori Tomono

Journal of medical virology   94 ( 7 )   3155 - 3159   2022.7

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We aimed to compare the differences in testing performance of extraction-based polymerase chain reaction (PCR) assays, elution-based direct PCR assay, and rapid antigen detection tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We used nasopharyngeal swab samples of patients with coronavirus disease 2019 (COVID-19). We used the MagNA Pure 24 System (Roche Diagnostics K.K.) or magLEAD 12gC (Precision System Science Co., Ltd.) for RNA extraction, mixed the concentrates with either the LightMix Modular SARS-CoV PCR mixture (Roche Diagnostics K.K.) or Takara SARS-CoV-2 direct PCR detection kit (Takara Bio Inc.), and amplified it using COBAS® z480 (Roche Diagnostics K.K.). For elution-based PCR, we directly applied clinical samples to the Takara SARS-CoV-2 direct PCR detection kit before the same amplification step. Additionally, we performed Espline SARS-CoV-2 (Fuji Rebio Co., Ltd.) for rapid diagnostic test (RDT), and used Lumipulse SARS-CoV-2 antigen (Fuji Rebio Co., Ltd.) and Elecsys SARS-CoV-2 antigen (Roche Diagnostics K.K.) for automated antigen tests (ATs). Extraction-based and elution-based PCR tests detected the virus up to 214-216 and 210 times dilution, respectively. ATs remained positive up to 24-26 times dilution, while RDT became negative after 22 dilutions. For 153 positive samples, positivity rates of the extraction-based PCR assay were 85.6% to 98.0%, while that of the elution-based PCR assay was 73.2%. Based on the RNA concentration process, extraction-based PCR assays were superior to elution-based direct PCR assays for detecting SARS-CoV-2.

DOI： 10.1002/jmv.27709

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Clinical Characteristics of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Diagnosed in Patients with Long COVID. Reviewed International journal

Kazuki Tokumasu, Hiroyuki Honda, Naruhiko Sunada, Yasue Sakurada, Yui Matsuda, Koichiro Yamamoto, Yasuhiro Nakano, Toru Hasegawa, Yukichika Yamamoto, Yuki Otsuka, Hideharu Hagiya, Hitomi Kataoka, Keigo Ueda, Fumio Otsuka

Medicina (Kaunas, Lithuania)   58 ( 7 )   2022.6

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Background and Objectives: COVID-19 can be serious not only in the acute phase but also after the acute phase and some patients develop ME/CFS. There have been few studies on patients with long COVID in whom ME/CFS was diagnosed by physicians based on standardized criteria after examinations and exclusion diagnosis and not based on only subjective symptoms. The purpose of this study was to elucidate the detailed characteristics of ME/CFS in patients with long COVID. Materials and Methods: A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period was from February 2021 to April 2022. Results: Clinical data were obtained from medical records for 281 patients, and 279 patients who met the definition of long COVID were included. The overall prevalence rate of ME/CFS diagnosed by three sets of ME/CFS criteria (Fukuda, Canadian and IOM criteria) was 16.8% (48.9% in male and 51.1% in females). The most frequent symptoms in ME/CFS patients were general fatigue and post-exertional malaise (89.4% of the patients), headache (34.0%), insomnia (23.4%), dysosmia (21.3%) and dysgeusia (19.1%). Dizziness, chest pain, insomnia and headache were characteristic symptoms related to ME/CFS. The male to female ratio in ME/CFS patients was equal in the present study, although ME/CFS was generally more common in women in previous studies. Given that patients with ME/CFS had more severe conditions in the acute phase of COVID-19, the severity of the acute infectious state might be involved in the pathophysiology of ME/CFS. Conclusions: The prevalence rate of ME/CFS and the characteristic sequelae in the long COVID condition were revealed in this study.

DOI： 10.3390/medicina58070850

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Trends in places and causes of death among centenarians in Japan from 2006 to 2016. Reviewed

Toshihiro Koyama, Tsukasa Higashionna, Akinori Maruo, Soichiro Ushio, Yoshito Zamami, Ko Harada, Hideharu Hagiya

Geriatrics & gerontology international   22 ( 8 )   675 - 680   2022.6

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AIM: Amid the global aging, an establishment of healthcare policies for the aged population is a common issue to be addressed. However, few studies on centenarians have reported place and cause of death (PoD and CoD, respectively) as indicators of end-of-life care quality. This study aimed to analyze trends in PoD and CoD among centenarians in Japan. METHODS: Data from death certificates from Japanese vital statistics were analyzed; 205 513 deaths occurred among centenarians (aged ≥100 years) in Japan during the period from 2006 to 2016. PoD prevalence was calculated for each CoD. Trends in PoD prevalence were analyzed using the Joinpoint regression model. Changing points, annual percentage changes, and average annual percentage changes (AAPCs) were calculated to examine trends. RESULTS: The number of deaths more than doubled from 10 340 in 2006 to 26 427 in 2016. PoDs were composed of hospitals (52.7%), nursing homes (31.4%), own homes (13.6%) and others (2.2%). Dementia and old age increased rapidly as CoD. Proportions of hospital and home deaths decreased, with AAPCs of -2.3% (95% confidence interval [CI], -2.6 to -1.9) and -2.3% (95% CI, -3.2 to -1.4), respectively. Conversely, the proportion of deaths in nursing homes rapidly increased, with an AAPC of 6.8% (95% CI, 6.0-7.7). CONCLUSIONS: The results revealed changes in PoD among centenarians in Japan. Understanding these transitions is indispensable for health policy in aging societies. Geriatr Gerontol Int 2022; ••: ••-••.

DOI： 10.1111/ggi.14416

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維持透析中の2型糖尿病患者に発症したフルニエ壊疽の1例

庵谷 紘美, 本多 寛之, 平 佑貴, 中本 健太, 中野 靖浩, 長谷川 功, 萩谷 英大, 小比賀 美香子, 片岡 仁美, 大塚 文男

糖尿病   65 ( 6 )   337 - 337   2022.6

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胸鎖関節炎・頸部膿瘍を契機に診断した2型糖尿病の1例

中本 健太, 本多 寛之, 平 佑貴, 庵谷 紘美, 中野 靖浩, 長谷川 功, 萩谷 英大, 小比賀 美香子, 片岡 仁美, 大塚 文男

糖尿病   65 ( 6 )   337 - 337   2022.6

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胸鎖関節炎・頸部膿瘍を契機に診断した2型糖尿病の1例

中本 健太, 本多 寛之, 平 佑貴, 庵谷 紘美, 中野 靖浩, 長谷川 功, 萩谷 英大, 小比賀 美香子, 片岡 仁美, 大塚 文男

糖尿病   65 ( 6 )   337 - 337   2022.6

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維持透析中の2型糖尿病患者に発症したフルニエ壊疽の1例

庵谷 紘美, 本多 寛之, 平 佑貴, 中本 健太, 中野 靖浩, 長谷川 功, 萩谷 英大, 小比賀 美香子, 片岡 仁美, 大塚 文男

糖尿病   65 ( 6 )   337 - 337   2022.6

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Application of Kampo Medicines for Treatment of General Fatigue Due to Long COVID. Reviewed International journal

Kazuki Tokumasu, Keigo Ueda, Hiroyuki Honda, Naruhiko Sunada, Yasue Sakurada, Yui Matsuda, Yasuhiro Nakano, Toru Hasegawa, Yuki Otsuka, Mikako Obika, Hideharu Hagiya, Hitomi Kataoka, Fumio Otsuka

Medicina (Kaunas, Lithuania)   58 ( 6 )   2022.5

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Evidence regarding treatment for the acute phase of COVID-19 has been accumulating, but specific treatment for long COVID/post-COVID-19 condition has not yet been established. Treatment with herbal medicine might be one treatment option for long COVID, but there has been little research on the effectiveness of herbal medicine for long COVID. The aim of this study was to clarify the prescription patterns of Kampo medicines, which are herbal medicines that originated in China and were developed in Japan, for the treatment of general fatigue due to long COVID. A retrospective descriptive study was performed for patients who visited a COVID-19 aftercare clinic established in Okayama University Hospital during the period from Feb 2021 to Dec 2021 with a focus on symptoms accompanying general fatigue and prescriptions of Kampo medicine. Among the clinical data obtained from medical records of 195 patients, clinical data for 102 patients with general fatigue and accompanying symptoms were analyzed. The patients had various symptoms, and the most frequent symptoms accompanying general fatigue were dysosmia, dysgeusia, headache, insomnia, dyspnea, and hair loss. Prescriptions of Kampo medicine accounted for 24.1% of the total prescriptions (n = 609). The most frequently prescribed Kampo medicine was hochuekkito (71.6%) and other prescribed Kampo medicines were tokishakuyakusan, ryokeijutsukanto, juzentaihoto, hangekobokuto, kakkonto, ninjin'yoeito, goreisan, rikkunshito, and keishibukuryogan. Since the pathophysiology of general fatigue after an infectious disease is, in general, considered a qi deficiency in Kampo medicine, treatments with such compensation agents can be the major prescription as a complement for the qi. In conclusion, Kampo medicine can be one of the main pharmacological treatments for long COVID accompanying general fatigue.

DOI： 10.3390/medicina58060730

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Call for correction: Mid and long-term neurological and neuropsychiatric manifestations of post-COVID-19 syndrome: A meta-analysis. Reviewed International journal

Hideharu Hagiya, Yuki Otsuka, Fumio Otsuka

Journal of the neurological sciences   436   120232 - 120232   2022.5

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Authorship：Lead author,　Corresponding author   Language：English  

DOI： 10.1016/j.jns.2022.120232

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Trends in sarcoidosis mortality rate in Japan from 2001 to 2020: A population-based study. Reviewed International journal

Ko Harada, Hideharu Hagiya, Toshihiro Koyama, Fumio Otsuka

Respiratory medicine   196   106828 - 106828   2022.5

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BACKGROUND: The sarcoidosis mortality rate has increased over the years, which contributes to the health care burden. Although epidemiological studies of sarcoidosis mortality in aging societies are essential, none have been published since 1989 in Japan. METHODS: We aimed to investigate the trends in crude and age-adjusted sarcoidosis-associated mortality rates per 1,000,000 population in Japan from 2001 to 2020 using national death certificate data among older adults aged over 50 years. The data were analysed using the joinpoint regression models to estimate long-term trends and average annual percentage changes (AAPCs). RESULTS: A total of 3094 sarcoidosis-associated deaths were recorded from 2001 to 2020 in Japan; women constituted 65.3% of these, with a female:male ratio of 1.89. Nearly 80% of deaths were over the age of 65 years, of which 32% were over the age of 80 years. The trend in crude mortality of those aged ≥80 years markedly increased from 0.81 to 9.68 per 1,000,000 population in men and from 2.38 to 12.87 in women, respectively. The overall age-adjusted sarcoidosis mortality rate increased 2.46-fold during the study period, with an AAPC of 5.1%. CONCLUSIONS: This study revealed that sarcoidosis-associated deaths in Japan have significantly increased over the past two decades, especially among the older population with a female predominance. Given the rising mortality rate and susceptibility of the older population, sarcoidosis will require more attention from health care providers in terms of a multidisciplinary approach to address the specific needs of the older population.

DOI： 10.1016/j.rmed.2022.106828

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Adverse reactions and attitudes toward vaccines among young populations one month after receiving a second dose of mRNA-1273 in Japan. Reviewed

Naomi Matsumoto, Chigusa Higuchi, Toshiharu Mitsuhashi, Hideharu Hagiya, Soshi Takao, Takashi Yorifuji

Global health & medicine   4 ( 2 )   141 - 143   2022.4

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To investigate adverse reactions and attitudes toward the vaccine during the first month after mRNA- 1273 vaccination in a larger sample including younger men and women in Japan, we distributed a 1-month post-vaccination questionnaire using a Google form to 8,566 people who received a second dose of mRNA-1273 at Okayama University. The response rate was about 40.2% (3,447 responses), the sex ratio was about the same, and 73.3 % (2,528 respondents) were students in their twenties or younger. Poisson regression with robust variance was performed to calculate the prevalence ratio of each symptom by different attributes. The most common adverse reactions after the second vaccine dose were local pain (80.4%), fever (85.1%), malaise (82.0%), headache (64.0%), and chills (57.4%). Approximately 99% of respondents reported that their adverse reactions resolved within 1 week. Over 80% of respondents were satisfied with their vaccination (87.2%), expressed interest in receiving the third vaccination (83.3%), and would recommend vaccination to their loved ones (80.2%). However, among them, 22.0% (757 respondents) would recommend and 28.4% (980 respondents) also stated that they would consider the type of vaccine in these decisions.

DOI： 10.35772/ghm.2021.01125

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Hormonal trends in patients suffering from long COVID symptoms. Reviewed

Naruhiko Sunada, Hiroyuki Honda, Yasuhiro Nakano, Koichiro Yamamoto, Kazuki Tokumasu, Yasue Sakurada, Yui Matsuda, Toru Hasegawa, Yuki Otsuka, Mikako Obika, Yoshihisa Hanayama, Hideharu Hagiya, Keigo Ueda, Hitomi Kataoka, Fumio Otsuka

Endocrine journal   69 ( 10 )   1173 - 1181   2022.4

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Symptoms of long COVID are complex and long-lasting, and endocrine dysfunction might be involved in the underlying mechanisms. In this study, to clarify the hormonal characteristics of long COVID patients, laboratory data for patients who visited the outpatient clinic for long COVID were evaluated. A retrospective analysis was performed for patients who visited Okayama University Hospital during the period from Feb 2021 to Dec 2021 with focus on the interrelationships between major symptoms and endocrine data. Information and laboratory data were obtained from medical records for 186 patients. The patients had various symptoms, and the most frequent symptoms were general malaise, dysosmia/dysgeusia, hair loss, headache, dyspnea, and sleeplessness. Patients who were suffering from fatigue and dysosmia/dysgeusia were younger, while hair loss was more frequent in older and female patients. As for the characteristics of patients suffering from general fatigue, the scores of depression and fatigue were positively correlated with serum levels of cortisol and free thyroxin (FT4), respectively. Also, patients suffering from general fatigue had lower levels of serum growth hormone and higher levels of serum FT4, while patients with dysosmia/dysgeusia had a significantly lower level of serum cortisol. Serum thyrotropin (TSH) levels were higher and the ratios of FT4/TSH were lower in the initially severe cases, suggesting occult hypothyroidism. In addition, the ratios of plasma adrenocorticotropin to serum cortisol were decreased in patients with relatively high titers of serum SARS-CoV-2 antibody. Thus, hormonal changes seem to be, at least in part, involved in the persistent symptoms of long COVID.

DOI： 10.1507/endocrj.EJ22-0093

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Late-Onset Hypogonadism in a Male Patient with Long COVID Diagnosed by Exclusion of ME/CFS. Reviewed International journal

Yoshiaki Soejima, Yuki Otsuka, Kazuki Tokumasu, Yasuhiro Nakano, Ko Harada, Kenta Nakamoto, Naruhiko Sunada, Yasue Sakurada, Kou Hasegawa, Hideharu Hagiya, Keigo Ueda, Fumio Otsuka

Medicina (Kaunas, Lithuania)   58 ( 4 )   2022.4

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After the acute phase of COVID-19, some patients have been reported to have persistent symptoms including general fatigue. We have established a COVID-19 aftercare clinic (CAC) to provide care for an increasing number of these patients. Here, we report the case of a 36-year-old man who developed post-COVID fatigue after acute infection with SARS-CoV-2. In the acute phase of COVID-19, the patient's fever resolved within four days; however, general fatigue persisted for three months, and he visited our CAC 99 days after the initial infection. Examination revealed a high Aging Male's Symptoms (AMS) score of 44 and low free testosterone (FT) level of 5.5 pg/mL, which meet the Japanese criteria of late-onset hypogonadism (LOH) syndrome. Imaging studies revealed an atrophic pituitary in addition to fatty liver and low bone mineral density. Anterior pituitary function tests showed a low follicle-stimulating hormonelevel and delayed reaction of luteinizing hormone (LH) after gonadotropin-releasing hormone (GnRH) stimulation, indicating the possibility of hypothalamic hypogonadism in addition to primary hypogonadism seen in patients with post-COVID-19 conditions. After the initiation of Japanese traditional medicine (Kampo medicine: hochuekkito followed by juzentaihoto), the patient's symptoms as well as his AMS score and serum FT level were noticeably improved. Furthermore, follow-up tests of GnRH stimulation revealed improvements in LH responsiveness. Although many patients have been reported to meet the criteria of ME/CFS such as our case, we emphasize the possibility of other underlying pathologies including LOH syndrome. In conclusion, LOH syndrome should be considered a cause of general fatigue in patients with post-COVID-19 conditions and herbal treatment might be effective for long COVID symptoms due to LOH (264 words).

DOI： 10.3390/medicina58040536

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Antimicrobial prescription practices for outpatients with uncomplicated cystitis in Japan. Reviewed International journal

Misa Takahashi, Hideharu Hagiya, Tsukasa Higashionna, Yasuhiro Nakano, Kota Sato, Yuto Haruki, Mai Haruki, Hiroyuki Honda, Hiroko Ogawa, Keigo Ueda, Fumio Otsuka

Scientific reports   12 ( 1 )   5921 - 5921   2022.4

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To promote antimicrobial stewardship, we studied antimicrobial prescription rates for uncomplicated cystitis, a common outpatient disease requiring antibiotic treatment. This multicenter retrospective study was performed from January 1, 2018, to December 31, 2020, in Japan, targeting outpatients aged ≥ 20 years whose medical records revealed International Classification of Diseases (ICD-10) codes suggesting uncomplicated cystitis (N300). The data of 1445 patients were collected and that of 902 patients were analyzed. The overall median patient age was 71 years and a proportion of those aged less than 50 years was 18.8% with a female dominance (82.6%). Antimicrobials were prescribed for 884 patients (98.0%) and a total of 623 patients (69.1%) were treated with broad-spectrum drugs, including fluoroquinolones (36.0%), third-generation cephalosporins (29.9%) and faropenem (3.1%). A logistic regression model revealed that the broad-spectrum agents were significantly prescribed for the older patients, male patients, and those who visited internists. Recurrence was observed in 37 (4.1%) cases, and the multivariate analysis suggested any of age, sex, or antimicrobial types were not associated with the recurrence. Collectively, approximately two-thirds of antimicrobials prescribed for uncomplicated cystitis were broad-spectrum agents. The present data would be an indicator for antimicrobial prescriptions in uncomplicated cystitis in Japan.

DOI： 10.1038/s41598-022-09946-8

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経過中に難治性高血圧症を合併した血管型Ehlers-Danlos症候群の1例

長谷川 功, 田中 秀一, 山本 紘一郎, 中野 靖浩, 本多 寛之, 萩谷 英大, 冨田 晃司, 戸田 洋伸, 内田 治仁, 平沢 晃, 大塚 文男

日本内分泌学会雑誌   98 ( 1 )   322 - 322   2022.4

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Cat scratch disease without a history of cat exposure. Reviewed International journal

Kosuke Oka, Yume Takagi, Hideharu Hagiya, Fumio Otsuka

Clinical case reports   10 ( 4 )   e04816   2022.4

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A patient complaining of swelling and tenderness in her left axilla was diagnosed with cat scratch disease despite no apparent history of cat exposure. Zoonosis can occur even in the absence of cat exposure because cat flea Ctenocephalides felis is also the vector of the pathogen through the flea feces.

DOI： 10.1002/ccr3.4816

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経過中に難治性高血圧症を合併した血管型Ehlers-Danlos症候群の1例

長谷川 功, 田中 秀一, 山本 紘一郎, 中野 靖浩, 本多 寛之, 萩谷 英大, 冨田 晃司, 戸田 洋伸, 内田 治仁, 平沢 晃, 大塚 文男

日本内分泌学会雑誌   98 ( 1 )   322 - 322   2022.4

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Detection of Male Hypogonadism in Patients with Post COVID-19 Condition. Reviewed International journal

Yukichika Yamamoto, Yuki Otsuka, Naruhiko Sunada, Kazuki Tokumasu, Yasuhiro Nakano, Hiroyuki Honda, Yasue Sakurada, Hideharu Hagiya, Yoshihisa Hanayama, Fumio Otsuka

Journal of clinical medicine   11 ( 7 )   2022.3

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The pathogenesis and prognosis of post COVID-19 condition have remained unclear. We set up an outpatient clinic specializing in long COVID in February 2021 and we have been investigating post COVID-19 condition. Based on the results of our earlier study showing that "general fatigue" mimicking myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is the most common symptom in long COVID patients, a retrospective analysis was performed for 39 male patients in whom serum free testosterone (FT) levels were measured out of 61 male patients who visited our clinic. We analyzed the medical records of the patients' backgrounds, symptoms and laboratory results. Among the 39 patients, 19 patients (48.7%) met the criteria for late-onset hypogonadism (LOH; FT &lt; 8.5 pg/mL: LOH group) and 14 patients were under 50 years of age. A weak negative correlation was found between age and serum FT level (r = -0.301, p = 0.0624). Symptoms including general fatigue, anxiety, cough and hair loss were more frequent in the LOH group than in the non-LOH group (FT ≥ 8.5 pg/mL). Among various laboratory parameters, blood hemoglobin level was slightly, but significantly, lower in the LOH group. Serum level of FT was positively correlated with the levels of blood hemoglobin and serum total protein and albumin in the total population, whereas these interrelationships were blurred in the LOH group. Collectively, the results indicate that the incidence of LOH is relatively high in male patients, even young male patients, with post COVID-19 and that serum FT measurement is useful for revealing occult LOH status in patients with long COVID.

DOI： 10.3390/jcm11071955

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Trends in the amyloidosis mortality rate in Japan: A nationwide observational study from 1998 to 2019. Reviewed

Ko Harada, Hideharu Hagiya, Toshihiro Koyama, Fumio Otsuka

Geriatrics & gerontology international   22 ( 3 )   246 - 250   2022.3

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AIM: Despite the increasing attention that has been paid to amyloidosis in recent years, there have been few reports on amyloidosis mortality and its trends worldwide. This study aimed to evaluate the trends in crude and age-adjusted amyloidosis-associated mortality rates in Japan from 1998 to 2019. METHODS: We used national Vital Statistics data among older adults aged over 50 years. The data were analyzed using the joinpoint regression program to estimate the long-term trends and average annual percentage changes (AAPCs). RESULTS: A total of 9158 amyloidosis-associated deaths were recorded from 1998 to 2019, of which 56.1% were in men. The crude mortality rate per 1 000 000 older adults aged over 80 years increased from 9.65 to 54.3 among men and from 7.02 to 22.1 among women during the study period. Overall, the AAPCs of age-adjusted amyloidosis-associated mortality rates increased significantly over the study period (1.8%, 95% confidence interval [CI], 1.0-2.7%). While the annual percentage change (APC) of age-adjusted mortality rates in women showed no significant change over the study period, the APC in men markedly increased in the 2013-2019 period (8.2%, 95% CI: 6.0-10.4%). CONCLUSIONS: This study revealed an increasing trend in mortality associated with amyloidosis, and in particular a marked increase in mortality among men over the past 6 years. Considering its high mortality rate and susceptibility to the effects of an increasing population of older adults, amyloidosis deserves more attention from healthcare providers to improve the understanding of diagnosis, clinical treatment, and healthcare planning. Geriatr Gerontol Int 2022; 22: 246-250.

DOI： 10.1111/ggi.14348

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コロナ・アフターケア外来から診断されたLOH症候群の1例

副島 佳晃, 中野 靖浩, 徳増 一樹, 大塚 勇輝, 櫻田 泰江, 本多 寛之, 中本 健太, 長谷川 功, 萩谷 英大, 植田 圭吾, 大塚 文男

日本内分泌学会雑誌   97 ( 5 )   1304 - 1304   2022.3

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初期研修医の卒後ローテーションにおける「感染症研修の必須化」に関するアンケート調査 Reviewed

萩谷 英大, 徳増 一樹, 小比賀 美香子, 大塚 文男

感染症学雑誌   96 ( 2 )   61 - 64   2022.3

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初期研修医の卒後ローテーションにおける「感染症研修の必須化」に関する意識などを明らかにすることを目的に、岡山県内で初期研修プログラムを有する16の研修病院に所属する初期研修医(卒後1・2年)、および専攻医(卒後3・4・5年)を対象にウェブ・アンケートを行い、127名(男性64名、女性60名、無回答3名)より回答を得た。その結果、初期研修医制度における「感染症研修の必須化」(例:最低1ヵ月ローテーションするなど)について84名(66.1%)が賛成すると回答した。一方、18名(14.2%)は必須化に反対しており、その理由として、「ローテーション選択の自由度を損なうため」(15名)などが挙げられた。

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Serial Changes of Long COVID Symptoms and Clinical Utility of Serum Antibody Titers for Evaluation of Long COVID. Reviewed International journal

Yasue Sakurada, Naruhiko Sunada, Hiroyuki Honda, Kazuki Tokumasu, Yuki Otsuka, Yasuhiro Nakano, Yoshihisa Hanayama, Masanori Furukawa, Hideharu Hagiya, Fumio Otsuka

Journal of clinical medicine   11 ( 5 )   2022.2

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BACKGROUND: Various symptoms persist even after the acute symptoms in about one third of patients with COVID-19. In February 2021, we established an outpatient clinic in a university hospital for patients with long COVID and started medical treatment for sequelae that persisted one month or more after infection. METHODS: To determine the key factors that affect the onset and clinical course of sequelae, a retrospective analysis was performed at Okayama University Hospital (Japan) between February and July 2021. We focused on changes in the numbers of symptoms and the background of the patients during a three-month period from the first outpatient visit. We also examined the relationship with SARS-CoV-2 antibody titers. RESULTS: Information was obtained from medical records for 65 patients. The symptoms of sequelae were diverse, with more than 20 types. The most frequent symptoms were general malaise, dysosmia, dysgeusia, sleeplessness, and headache. These symptoms improved in about 60% of the patients after 3 months. Patients who required hospitalization and had a poor condition in the acute phase and patients who received oxygen/dexamethasone therapy had higher antibody titers at the time of consultation. Patients with antibody titers ≥200 U/mL showed significantly fewer improvements in long COVID symptoms in 1 month, but they showed improvements at 3 months after the first visit. CONCLUSION: Long COVID symptoms were improved at 3 months after the initial visit in more than half of the patients. Serum antibody titers were higher in patients who experienced a severe acute phase, but the serum antibody titers did not seem to be directly related to the long-term persistence of long COVID symptoms.

DOI： 10.3390/jcm11051309

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Foramen of Winslow Hernia Ameliorating Conservatively. Reviewed

Hiroyuki Honda, Hiroyuki Sakae, Hideharu Hagiya, Fumio Otsuka

Internal medicine (Tokyo, Japan)   61 ( 18 )   2817 - 2818   2022.2

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DOI： 10.2169/internalmedicine.8950-21

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Clinical Utility of 4C Mortality Scores among Japanese COVID-19 Patients: A Multicenter Study. International journal

Kazuki Ocho, Hideharu Hagiya, Kou Hasegawa, Kouji Fujita, Fumio Otsuka

Journal of clinical medicine   11 ( 3 )   2022.2

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BACKGROUND: We analyzed data from COVID-19 patients in Japan to assess the utility of the 4C mortality score as compared with conventional scorings. METHODS: In this multicenter study, COVID-19 patients hospitalized between March 2020 and June 2021, over 16 years old, were recruited. The superiority for correctly predicting mortality and severity by applying the receiver operating characteristic (ROC) curve was compared. A Cox regression model was used to compare the length of hospitalization for each risk group of 4C mortality score. RESULTS: Among 206 patients, 21 patients died. The area under the curve (AUC) (95% confidential interval (CI)) of the ROC curve for mortality and severity, respectively, of 4C mortality scores (0.84 (95% CI 0.76-0.92) and 0.85 (95% CI 0.80-0.91)) were higher than those of qSOFA (0.66 (95% CI 0.53-0.78) and 0.67 (95% CI 0.59-0.75)), SOFA (0.70 (95% CI 0.55-0.84) and 0.81 (95% CI 0.74-0.89)), A-DROP (0.78 (95% CI 0.69-0.88) and 0.81 (95% CI 0.74-0.88)), and CURB-65 (0.82 (95% CI 0.74-0.90) and 0.82 (95% CI 0.76-0.88)). For length of hospitalization among survivors, the intermediate- and high- or very high-risk groups had significantly lower hazard ratios, i.e., 0.48 (95% CI 0.30-0.76)) and 0.23 (95% CI 0.13-0.43) for discharge. CONCLUSIONS: The 4C mortality score is better for estimating mortality and severity in COVID-19 Japanese patients than other scoring systems.

DOI： 10.3390/jcm11030821

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岡山大学病院におけるCOVID-19アフターケア外来の取り組み

大塚 勇輝, 徳増 一樹, 中野 靖浩, 本多 寛之, 萩谷 英大, 砂田 匠彦, 大村 大輔, 櫻田 泰江, 小比賀 美香子, 大塚 文男

日本内科学会雑誌   111 ( Suppl. )   214 - 214   2022.2

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Threat of Staphylococcus aureus Pneumonia in Severe COVID-19 Patients. International journal

Shuichi Tanaka, Koichiro Yamamoto, Hideharu Hagiya, Kou Hasegawa, Fumio Otsuka

Cureus   14 ( 2 )   e22486   2022.2

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Coronavirus disease 2019 (COVID-19) has been spreading worldwide with unprecedented rapidity. Staphylococcus aureus is reported to frequently cause bacterial complications in patients with COVID-19. We herein present two additional cases of S. aureus pneumonia involving such patients. The first case was an obese 48-year-old man without any particular underlying diseases. The second case was another patient, a 72-year-old man, with hypertension, dyslipidemia, and steatohepatitis. Both patients developed methicillin-susceptible S. aureus pneumonia in the clinical course of COVID-19, to which antibiotic therapy with cefazolin was effectively administered. Through these cases, we emphasize that S. aureus secondary infections should be well cared with a high degree of caution in a case of critically ill COVID-19 patients.

DOI： 10.7759/cureus.22486

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Aging-related Characteristics of Subclinical Hypothyroidism Detected in General Practice.

Masao Takami, Koichiro Yamamoto, Yoshihisa Hanayama, Yasuhiro Nakano, Kou Hasegawa, Mikako Obika, Hideharu Hagiya, Masanori Furukawa, Fumio Otsuka

Acta medica Okayama   76 ( 1 )   7 - 15   2022.2

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Subclinical hypothyroidism (SCH) is diagnosed when serum thyrotropin (TSH) is elevated despite a normal thyroxine level and is known to increase the risk of metabolic disorders. This study was conducted to identify potential laboratory markers suspicious for latent SCH. We retrospectively reviewed 958 outpatients in whom thyroid functions had been examined. Eighty-five (9.1%) of the 939 analyzed subjects had SCH (73% females). In the SCH group, median serum TSH and FT4 levels were 5.04 μU/ml and 1.19 ng/dl, respectively, and auto-thyroid antibodies were detected in 53.8% of patients. SCH group patients were significantly older than patients in the euthyroid group, while there was no intergroup difference in BMI. However, 56.5% of the SCH patients were asymptomatic. In the SCH group, serum aspartate aminotransferase and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher, and the estimated glomerular filtration rate (eGFR) was significantly lower than in the euthyroid group. Among patients less than 65 years of age, SCH patients tended to have lower eGFR and higher LDL-C than euthyroid patients. Age-dependent reductions of red blood cells and serum albumin were more prominent in the SCH than the euthyroid group. Biochemical changes with aging are useful as potential clues for suspecting latent SCH.

DOI： 10.18926/AMO/63203

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COVID-19後遺症状の診療において大学病院総合内科が果たせる役割

大塚 勇輝, 徳増 一樹, 中野 靖浩, 本多 寛之, 萩谷 英大, 砂田 匠彦, 櫻田 泰江, 山本 幸近, 大村 大輔, 松田 祐依, 長谷川 功, 小比賀 美香子, 植田 圭吾, 片岡 仁美, 大塚 文男

日本病院総合診療医学会雑誌   18 ( 臨増1 )   N - 010   2022.2

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COVID-19後遺症状の診療において大学病院総合内科が果たせる役割

大塚 勇輝, 徳増 一樹, 中野 靖浩, 本多 寛之, 萩谷 英大, 砂田 匠彦, 櫻田 泰江, 山本 幸近, 大村 大輔, 松田 祐依, 長谷川 功, 小比賀 美香子, 植田 圭吾, 片岡 仁美, 大塚 文男

日本病院総合診療医学会雑誌   18 ( 臨増1 )   N - 010   2022.2

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Bull's Head Sign.

Koichiro Yamamoto, Hiroyuki Honda, Hideharu Hagiya, Fumio Otsuka

JMA journal   5 ( 1 )   130 - 131   2022.1

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DOI： 10.31662/jmaj.2021-0129

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Therapeutic Drug Monitoring for Aminoglycosides: Not Yet Readily Available in Japanese University Hospitals.

Hideharu Hagiya, Fumio Otsuka

JMA journal   5 ( 1 )   127 - 129   2022.1

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DOI： 10.31662/jmaj.2021-0134

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Recovery From Alopecia After COVID-19. International journal

Yuki Otsuka, Yasuhiro Nakano, Hideharu Hagiya, Kazuki Tokumasu, Fumio Otsuka

Cureus   14 ( 1 )   e21160   2022.1

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Herein, we report a remarkable case of post-coronavirus disease 2019 (COVID-19) diffuse alopecia that gradually improved and recovered, and the hair volume returned approximately to the pre-infection level, seven months after the patient's first diagnosis of COVID-19. Approximately 20% of patients with COVID-19 develop alopecia a few months after the acute infection phase. Telogen effluvium is the major type of COVID-19 sequela secondary to physical or psychological distress. It is reversible and is expected to improve without any treatment, and it can be addressed by explaining to the patients their conditions, sharing medical information, and eliminating psychophysical stress by managing systemic complications.

DOI： 10.7759/cureus.21160

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COVID-19 mRNA Vaccine–Associated Uveitis Leading to Diagnosis of Sarcoidosis: Case Report and Review of Literature

Toshihiko Matsuo, Hiroyuki Honda, Takehiro Tanaka, Kensuke Uraguchi, Masaaki Kawahara, Hideharu Hagiya

Journal of Investigative Medicine High Impact Case Reports   10   232470962210864 - 232470962210864   2022.1

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Publishing type：Research paper (scientific journal)   Publisher：SAGE Publications  

A 34-year-old Japanese person with male gender identity who had been taking intramuscular injection of methyltestosterone depot for 11 years after bilateral mastectomy noticed blurred vision 5 days after the second vaccination for COVID-19 (Tozinameran; Pfizer-BioNTech) in the interval of 3 weeks following the first vaccination. The patient was diagnosed as granulomatous iritis with mutton-fat keratic precipitates and small iris nodules at the pupillary margin in the right eye and began to have 0.1% betamethasone eye drops with good response. The patient, however, continued to have fever and malaise and showed a high level of serum soluble interleukin-2 receptor (sIL-2R) even 4 weeks after the second vaccination. Computed tomographic scan disclosed mediastinal and bilateral hilar small lymphadenopathy together with limited granular lesion in the right lung. Gallium-67 scintigraphy demonstrated high uptake not only in mediastinal and hilar lymph nodes but also in bilateral parotid glands. Right parotid gland biopsy revealed noncaseating granulomas and proved pathological diagnosis of sarcoidosis. The systemic symptoms were relieved by oral prednisolone 20 mg daily. Even though the causal relationship remains undetermined, this case is unique at the point that vaccine-associated uveitis led to the detection of pulmonary lesions and lymphadenopathy, resulting in clinical and pathological diagnosis of sarcoidosis. In literature review, 3 patients showed sarcoidosis-like diseases after COVID-19 vaccination: 2 patients were diagnosed clinically as Lofgren syndrome with acute onset of erythema nodosum and ankle swelling, with or without mediastinal and hilar lymphadenopathy, whereas 1 patient with mediastinal lymphadenopathy but no uveitis was diagnosed pathologically by biopsy as sarcoidosis.

DOI： 10.1177/23247096221086450

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Interest in Infectious Diseases specialty among Japanese medical students amidst the COVID-19 pandemic: A web-based, cross-sectional study. International journal

Hideharu Hagiya, Yuki Otsuka, Kazuki Tokumasu, Hiroyuki Honda, Yoshito Nishimura, Mikako Obika, Fumio Otsuka

PloS one   17 ( 4 )   e0267587   2022

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INTRODUCTION: The emergence of the novel coronavirus disease of 2019 (COVID-19) has led to huge disruptions in the medical field and society. The significance of training and education for experts has been increasingly acknowledged in Japan, where the number of infectious disease (ID) specialists is reportedly insufficient. In this paper, we report the results of a web-based survey that was conducted to reveal the ways in which the COVID-19 pandemic has influenced medical students' awareness of ID specialists and future career choices. METHOD: This cross-sectional descriptive study was conducted in March 2021 and targeted 717 medical students belonging to Medical School of Okayama University, Japan. The questionnaire consisted of four questions meant to assess students' knowledge and future intentions of becoming ID specialists. RESULTS: We obtained 328 eligible questionnaires (response rate: 45.7%). Of 227 (69.2%) students who were aware of ID specialists, 99 (43.6%) answered that they came to know about them only after the pandemic, 12 (3.7%) answered that their interest in being an ID specialist arose during the pandemic, while 36 (11.0%) responded that they would rather not become ID specialists. At the time of the survey, 5 students (1.5%) were aiming to become ID specialists. CONCLUSION: We observed a very low rate of interest to be an ID specialist among medical students. The experience of the pandemic does not seem to have influenced Japanese medical students to choose ID as a specialty for their careers. Continuous efforts to increase the number of ID specialists are necessary in Japan as a countermeasure against the coming pandemic.

DOI： 10.1371/journal.pone.0267587

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Fear of an unprecedented, invisible enemy: Difficulties experienced in establishing criteria for the release of COVID-19 patients from isolation in a Japanese University Hospital. International journal

Hideharu Hagiya, Kou Hasegawa, Fumio Otsuka

PloS one   17 ( 4 )   e0266853   2022

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INTRODUCTION: The novel coronavirus disease 2019 (COVID-19) has emerged as a global pandemic, and the United States and European authorities established criteria for the release of COVID-19 patients from isolation in October 2020. However, a huge discrepancy exists between the hospital-discharge protocol for COVID-19 patients and the release of patients from in-hospital isolation. Our initially proposed criteria for in-hospital release from isolation was not adhered to by healthcare workers (HCWs) due to prevailing concerns regarding disease infectivity. Herein, we report difficulties encountered in attempting to establish a common understanding of the management of emerging infections. METHODS: We performed a Google Form-based questionnaire survey targeting HCWs from Okayama University Hospital, Japan, via e-mail on January 21-28, 2021. The anonymous investigation required respondents to provide information regarding their background as well as perceptions regarding the requirement, level of understanding, and readiness for developing release criteria. RESULTS: We obtained 150 eligible responses, including 57 (38.0%) from medical doctors and 53 (35.3%) from nurses. Most HCWs managing COVID-19 patients advocated for the implementation of the criteria, whereas those not working in that capacity did not (p<0.001). Over half of the HCWs indicated discomfort at seeing COVID-19 patients transitioning to general management even after meeting the criteria. CONCLUSIONS: It was challenging to establish a common understanding regarding the ideal criteria for in-hospital release of COVID-19 patients from isolation in our hospital. The dissemination of our experiences and multifaceted discussions with HCWs would be of great value as a countermeasure against the emergent pandemic.

DOI： 10.1371/journal.pone.0266853

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Adult-onset Mild Encephalitis/Encephalopathy with a Reversible Splenial Lesion Induced by MRSA Endocarditis. International journal

Hideharu Hagiya, Fumio Otsuka

European journal of case reports in internal medicine   9 ( 2 )   003185 - 003185   2022

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Background: Mild encephalitis/encephalopathy and a reversible splenial lesion (MERS) is a clinicoradiological syndrome with an unknown pathogenic mechanism, which usually involves children. Thus, adult-onset MERS is quite rare. Case presentation: A 71-year-old man, undergoing haemodialysis due to diabetes-induced chronic kidney disease, manifested a persistent fever and disorientation. Blood culture detected methicillin-resistant Staphylococcus aureus (MRSA), while echocardiography revealed vegetation in the aortic and mitral valves. Magnetic resonance imaging of the head revealed a fluid-attenuated inversion recovery-high, diffusion-weighted image-high lesion in the splenium of the corpus callosum, with a number of emboli. Accordingly, the patient was diagnosed with MERS induced by MRSA endocarditis. Discussion: Neurological impairment by MERS can be reversible. However, the differential diagnosis of the disease includes ischaemic lesions, multiple sclerosis, malignant lymphoma, acute disseminated encephalomyelitis, and posterior reversible encephalopathy. Clinicians should consider these diseases when MERS is suspected. LEARNING POINTS: Adult-onset mild encephalitis/encephalopathy and a reversible splenial lesion (MERS) is quite rare, and physicians should be aware of it as a differential diagnosis of a diffusion-weighted image-high lesion in the splenium of the corpus callosum.Methicillin-resistant Staphylococcus aureus (MRSA) has rarely been reported as a triggering factor for MERS.

DOI： 10.12890/2022_003185

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Association between fever and antibody titer trends after a third dose of the mRNA-1273 vaccine

Naomi Matsumoto, Tomoka Kadowaki, Rumi Matsuo, Ayako Sasaki, Chikara Miyaji, Chigusa Higuchi, Masanori Nakayama, Yasue Sakurada, Hideharu Hagiya, Soshi Takao, Fumio Otsuka, Takashi Yorifuji

Journal of Epidemiology   32 ( 12 )   567 - 569   2022

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DOI： 10.2188/jea.je20220210

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Trends in the Incidence of Syphilis in the Middle-aged and Older Adults in Japan: A Nationwide Observational Study, 2009–2019 Reviewed

Takahashi M, Hagiya H, Koyama T, Otsuka F

Geriatr Gerontol Int   22 ( 12 )   1019 - 1024   2022

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

AIM: Sexually transmitted infections remain a neglected area of research in geriatrics. However, in the global aging societies, sexual health among the middle-aged and older adults is an emerging public concern. High-income countries are facing a resurgence of syphilis cases among young generations, but little is known about its prevalence in older populations. We aimed to investigate the national trend of syphilis cases in Japan. METHODS: This nationwide observational study used the publicly-available database (2009-2019) to calculate crude and age-adjusted incidence rates of syphilis per 100 000 population by age, sex and clinical stage. We collected data from patients aged ≥50 years and performed joinpoint regression analysis to estimate long-term trends and average annual percentage changes (AAPCs). RESULTS: The total number of patients with syphilis increased about 8-fold from 165 in 2009 to 1280 in 2019. AAPCs of crude incidence rates significantly increased in every age category; 33.2% in 50-59 years, 23.8% in 60-69 years and 20.9% in ≥70 years. Age-adjusted incidence rates have surged at AAPCs of 28.7% in men and 23.1% in women, reaching 4.09 in men and 0.71 in women in 2019. By clinical stage, marked increases were observed in primary (AAPCs, 42.3% in men and 41.6% in women) and secondary syphilis (AAPCs, 24.9% in men and 24.2% in women). CONCLUSIONS: An up-toward trend of syphilis among people aged ≥50 years was observed. The importance of sexual health among older people should be highlighted in this aging Japanese society. Geriatr Gerontol Int 2022; 22: 1019-1024.

DOI： 10.1111/ggi.14500

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Comment on: Short versus prolonged courses of antimicrobial therapy for patients with uncomplicated Pseudomonas aeruginosa bloodstream infection: a retrospective study. International journal

Hideharu Hagiya, Fumio Otsuka

The Journal of antimicrobial chemotherapy   77 ( 3 )   857 - 858   2021.12

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DOI： 10.1093/jac/dkab464

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The illusionary correlation in antibiotic prescriptions: It may exist but requires further elucidation with rigorous methodology. International journal

Hideharu Hagiya, Akiko Aoki, Takahiro Matsuo, Masahiro Ishikane, Hiroaki Nakagawa, Takashi Yoshioka

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America   75 ( 1 )   176 - 176   2021.12

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DOI： 10.1093/cid/ciab1011

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Anti-Glomerular Basement Membrane Nephritis Potentially Induced by Nebulized Tobramycin Inhalation. International journal

Chie Inoue, Hideharu Hagiya

Journal of aerosol medicine and pulmonary drug delivery   35 ( 2 )   104 - 106   2021.12

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Objective: To describe a case of anti-glomerular basement membrane (GBM) nephritis that occurred shortly after initiation of nebulized tobramycin (TOB) therapy using intravenous solution, suggesting an association with the inhalation therapy and the disease onset. Background: With the emergence of antimicrobial resistance, clinical importance of aminoglycosides that usually remain susceptibility against gram-negative organisms is increasingly acknowledged. Despite the growing number of evidence supporting the effectiveness of aminoglycoside inhalation therapy for respiratory tract infections, its clinical application has yet to be widely approved by Japanese health insurance. Case Presentation: A 79-year-old Japanese woman had developed amyotrophic lateral sclerosis and experienced recurrent pneumonia mainly caused by Pseudomonas aeruginosa, which required monthly treatments with broad-spectrum antibiotics. Owing to the limited approval, we had no choice but to use intravenous TOB solution for inhalation therapy as an off-label use under an endorsement of the Institutional Review Board of the hospital. Although the repeated pneumonia subsided, the patient subsequently needed immunosuppressive therapy along with plasma exchanges for the treatment of anti-GBM nephritis. Conclusion: Although this off-label use of intravenous solutions is common in both clinical and research purposes, our case raised an issue that its safety needs to be re-evaluated.

DOI： 10.1089/jamp.2021.0053

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総合診療における甲状腺機能低下状態の潜在とその特徴

高見 優男, 山本 紘一郎, 花山 宜久, 中野 靖浩, 長谷川 功, 小比賀 美香子, 萩谷 英大, 大塚 文男

日本内分泌学会雑誌   97 ( 4 )   961 - 961   2021.12

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COVID-19後の倦怠感を契機に発見されたLOH症候群の1例

副島 佳晃, 中野 靖浩, 中本 健太, 大塚 勇輝, 櫻田 泰江, 徳増 一樹, 本多 寛之, 長谷川 功, 萩谷 英大, 大塚 文男

日本内分泌学会雑誌   97 ( 4 )   958 - 958   2021.12

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総合診療における甲状腺機能低下状態の潜在とその特徴

高見 優男, 山本 紘一郎, 花山 宜久, 中野 靖浩, 長谷川 功, 小比賀 美香子, 萩谷 英大, 大塚 文男

日本内分泌学会雑誌   97 ( 4 )   961 - 961   2021.12

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COVID-19後の倦怠感を契機に発見されたLOH症候群の1例

副島 佳晃, 中野 靖浩, 中本 健太, 大塚 勇輝, 櫻田 泰江, 徳増 一樹, 本多 寛之, 長谷川 功, 萩谷 英大, 大塚 文男

日本内分泌学会雑誌   97 ( 4 )   958 - 958   2021.12

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Burnout of Healthcare Workers Amid the COVID-19 Pandemic: A Follow-Up Study. International journal

Yoshito Nishimura, Tomoko Miyoshi, Asuka Sato, Kou Hasegawa, Hideharu Hagiya, Yoshinori Kosaki, Fumio Otsuka

International journal of environmental research and public health   18 ( 21 )   2021.11

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The coronavirus disease 2019 (COVID-19) pandemic has posed a significant challenge to the modern healthcare system and led to increased burnout among healthcare workers (HCWs). We previously reported that HCWs who engaged in COVID-19 patient care had a significantly higher prevalence of burnout (50.0%) than those who did not in November 2020 (period 1). We performed follow-up surveys in HCWs in a Japanese national university hospital, including basic demographics, whether a participant engaged in care of COVID-19 patients in the past 2 weeks, and the Maslach Burnout Inventory in February 2021 (period 2) and May 2021 (period 3). Periods 1 and 3 were amid the surges of COVID-19 cases, and period 2 was a post-surge period with a comparatively small number of COVID-19 patients requiring hospitalization. Response rates to the surveys were 33/130 (25.4%) in period 1, 36/130 (27.7%) in period 2, and 56/162 (34.6%) in period 3, respectively. While no consistent tendency in the prevalence of burnout based on variables was observed throughout the periods, the prevalence of burnout tends to be higher in periods 1 and 3 in those who engaged in COVID-19 patient care in the last 2 weeks (50.0%, 30.8%, 43.1% in period 1, 2, and 3, respectively). Given the prolonged pandemic causing stigmatization and hatred against HCWs leading to increased prevalence of burnout, high-level interventions and supports are warranted.

DOI： 10.3390/ijerph182111581

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Clinical utility of urinary levels of catecholamines and their fraction ratios related to heart rate and thyroid function.

Naruhiko Sunada, Yoshihisa Hanayama, Koichiro Yamamoto, Yasuhiro Nakano, Takahiro Nada, Hiroyuki Honda, Kou Hasegawa, Hideharu Hagiya, Fumio Otsuka

Endocrine journal   69 ( 4 )   417 - 425   2021.11

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Urinary catecholamines (CAs) have been examined for the screening of pheochromocytomas. The decision to perform screening is based on symptoms suggesting secondary hypertension or hyperactivities of the sympathetic nervous system. To elucidate the usefulness of urinary fractions and ratios of CAs, 79 patients in whom 24-h excretions of urinary CAs including adrenaline (AD), noradrenaline (NA) and dopamine (DA) had been examined from 2015 until 2020 were retrospectively analyzed. There were no significant differences in urinary CA levels between two age groups, gender groups and two BMI groups. Patients with histories of preexisting hypertension and diabetes showed significantly higher levels of urinary NA excretion, and the urinary ratio of NA/DA was also increased in the patients with a history of hypertension. Heart rate (HR) was significantly correlated with the urinary ratio of NA/DA. Serum free thyroxine (FT4) concentration and ratio of FT4/thyrotropin (TSH) were correlated with the level of urinary AD. The levels of TSH and FT4/TSH showed negative and positive correlations, respectively, with the urinary NA/DA ratio. Thus, increases of HR are related to the enhanced conversion of DA to NA and increased thyroid hormones are involved in the increase in urinary AD and the conversion of DA to NA. History of lifestyle-related diseases and changes of HR and thyroid functions need to be considered for the evaluation of urinary CAs and their ratios.

DOI： 10.1507/endocrj.EJ21-0488

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The clinical value of penicillin G outweighs its usage restriction due to a too-much concern for hyperkalemia. International journal

Hideharu Hagiya, Haruto Yamada, Shiho Kajita, Yoshitaka Iwamoto, Naofumi Hara

Journal of chemotherapy (Florence, Italy)   34 ( 4 )   1 - 2   2021.11

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DOI： 10.1080/1120009X.2021.1994689

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Emphysematous gastritis. International journal

Ryosuke Takase, Naoko Fukuda, Osamu Sui, Hideharu Hagiya

Clinical case reports   9 ( 11 )   e05094   2021.11

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An 89-year-old woman who had type 2 diabetes mellitus suddenly presented with abdominal pain. Abdominal computed tomography showed thickening of the wall and intramural gas in the gastric hilum, suggesting emphysematous gastritis. The patient underwent treatment with a proton-pump inhibitor and broad-spectrum antibacterial agents.

DOI： 10.1002/ccr3.5094

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【COVID-19-その診断と治療】倦怠感

大塚 勇輝, 徳増 一樹, 本多 寛之, 萩谷 英大, 大塚 文男

カレントテラピー   39 ( 11 )   1034 - 1039   2021.11

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新型コロナウイルス感染症(COVID-19)が最初に報告されてからおよそ1年半が経過したが、いまだ収束の兆しの見えない世界的流行のなかで「Long-COVID」ないし「post-acute sequelae of COVID-19(PASC)」と定義され、一般には「コロナ後遺症」として知られる、急性期以降に残存する症状に悩まされる患者が多く存在している。そのなかでも「倦怠感」は、最も多い症状として報告され、COVID-19罹患後に4割程度の患者が自覚すると言われている。倦怠感は視認できず検査での客観的評価も難しい症状である一方で、さまざまな要因が複雑に絡みあって生じており病態メカニズムも未解明なところが多く、診療に難渋する。われわれは2021年2月にLong-COVID/PASCを専門的に診療する「コロナ・アフターケア(COVID-19 aftercare:CAC)外来」を大学病院内にいち早く設立し、倦怠感などの症状に悩む患者の診療と研究・教育に取り組んできた。本稿ではそうしたわれわれの診療経験も踏まえ、診断や治療を行ううえでの対面診療の必要性や総合診療的アプローチの重要性についても触れながら、Long-COVID/PASCにおける倦怠感について概説する。(著者抄録)

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Evaluation of the influence of stimulus payments on the motivation of healthcare workers in the fight against the novel coronavirus disease 2019

萩谷英大, 三好智子, 西村義人, 徳増一樹, 本多寛之, 長谷川功, 小比賀美香子, 頼藤貴志, 大塚文男

日本病院総合診療医学会雑誌(Web)   17 ( 6 )   608 - 616   2021.11

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Impact of the world hand hygiene and global handwashing days on public awareness between 2016 and 2020: Google trends analysis. International journal

Yoshito Nishimura, Hideharu Hagiya, Koichi Keitoku, Toshihiro Koyama, Fumio Otsuka

American journal of infection control   50 ( 2 )   141 - 147   2021.10

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BACKGROUND: Scientific evidence suggest that hand hygiene as one of the most effective measures to control infection. To promote good hand hygiene practices, the World Health Organization introduced May 5 as World Hand Hygiene Day (WHHD), and international stakeholders established Global Handwashing Day (GHD) on October 15. However, its contributions to raising public awareness of hand hygiene is unclear. METHODS: This study evaluates the impact of the WHHD and GHD on the public awareness of hand hygiene in Japan, the United Kingdom, the United States, and worldwide from 2016 to 2020, using the relative search volume of "Hand hygiene" in Google Trends as a surrogate. To identify a statistically significant timepoint of a trend change, we performed Joinpoint regression analysis. RESULTS: Upticks of the relative search volumes as well as joinpoints were noted worldwide around the WHHD and GHD from 2016 to 2019, but no joinpoints were identified around the WHHD and GHD in 2020. No such changes were observed in Japan, the United Kingdom, and the United States during these periods. CONCLUSIONS: While the WHHD was originally established to raise awareness of hand hygiene in healthcare facilities, our result suggests that the WHHD and GHD may not have effectively disseminated the importance of hand hygiene to the general public at a country level. Additional policy measures to advocate hand hygiene to the public are necessary to communicate its benefits.

DOI： 10.1016/j.ajic.2021.08.033

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Impact of the World Inflammatory Bowel Disease Day and Crohn’s and Colitis Awareness Week on Population Interest Between 2016 and 2020: Google Trends Analysis

Krixie Silangcruz, Yoshito Nishimura, Torrey Czech, Nobuhiko Kimura, Hideharu Hagiya, Toshihiro Koyama, Fumio Otsuka

JMIR Infodemiology   2021.10

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DOI： 10.2196/32856

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Detection of in-frame mutation by IS30-family insertion sequence in the phospholipid phosphatidylglycerol synthase gene (pgsA2) of high-level daptomycin-resistant Corynebacterium striatum. International journal

Kazuyoshi Gotoh, I Putu Bayu Mayura, Yusaku Enomoto, Koji Iio, Osamu Matsushita, Fumio Otsuka, Hideharu Hagiya

European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology   41 ( 2 )   331 - 333   2021.10

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The emergence of high-level daptomycin (DAP)-resistant (HLDR) Corynebacterium striatum has been reported as a result of loss-of-function point mutations or premature stop codon mutations in a responsible gene, pgsA2. We herein describe the novel detection of an HLDR C. striatum clinical isolate, in which IS30-insertion was corroborated to cause destruction of pgsA2 gene. We isolated an HLDR C. striatum from a critically ill patient with underlying mycosis fungoides who had been treated with DAP for 10 days. With a sequence investigation, IS30-insertion was discovered to split pgsA2 in the HLDR C. striatum strain, which may cause disrupted phospholipid phosphatidylglycerol (PG) production. Future studies should survey the prevalence of IS-mediated gene inactivation among HLDR C. striatum clinical isolates.

DOI： 10.1007/s10096-021-04369-1

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Impact of the day of the week on the discontinuation of broad-spectrum antibiotic prescriptions; a multi-centered observational study. International journal

Hiroyuki Honda, Hideharu Hagiya, Tsukasa Higashionna, Yuto Haruki, Mai Haruki, Shiho Kajita, Kengo Mukuda, Yuji Yokoyama, Yasuhiro Nakano, Hiroko Ogawa, Yasuyo Morimoto, Yoshihisa Hanayama, Setsuko Kanda, Hitomi Kataoka, Hitomi Muguruma, Fumio Otsuka

Scientific reports   11 ( 1 )   20784 - 20784   2021.10

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To encourage and guide antimicrobial stewardship team (AST) activity and promote appropriate antibiotic use, we studied the impact of day of the week on the initiation and discontinuation of antibiotic administration. This was a multicenter observational study conducted at 8 Japanese hospitals from April 1 to September 30, 2019, targeting patients who underwent treatment with broad-spectrum antibiotics, such as anti-methicillin-resistant Staphylococcus aureus agents and anti-pseudomonal agents. We compared the weekly numbers of initiations and discontinuations of antibiotic prescription on each day of the week or on the days after a holiday. There was no statistical difference in the number of antibiotic initiations on both weekdays and the day after a holiday. However, antibiotic discontinuation was significantly higher from Tuesday onward than Monday and from the second day than the first day after a holiday. Similar trends were observed regardless of the categories of antibiotics, hospital and admission ward, and AST activity. This study suggests that broad-spectrum antibiotics tend to be continued during weekends and holidays and are most likely to be discontinued on Tuesday or the second day after a holiday. This was probably due to behavioral factors beyond medical indications, requiring further antimicrobial stewardship efforts in the future.

DOI： 10.1038/s41598-021-00206-9

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Calcified spleen associated with Pneumocystis jirovecii infection. International journal

Koichiro Yamamoto, Hiroyuki Honda, Hideharu Hagiya, Fumio Otsuka

QJM : monthly journal of the Association of Physicians   2021.10

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DOI： 10.1093/qjmed/hcab260

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Impact of the World Antimicrobial Awareness Week on public interest between 2015 and 2020: A Google Trends analysis. International journal

Koichi Keitoku, Yoshito Nishimura, Hideharu Hagiya, Toshihiro Koyama, Fumio Otsuka

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases   111   12 - 20   2021.10

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OBJECTIVES: To evaluate the impact of the World Antimicrobial Awareness Week (WAAW) on public awareness of antimicrobial resistance using Google Trends analysis. METHODS: The impact of WAAW on public awareness of 'antimicrobial resistance' (AMR), 'antibacterial', and 'antibiotics' in Japan, the UK, the United States, and worldwide from 2015 to 2020 was analyzed, using the relative search volume (RSV) of Google Trends as a surrogate. A joinpoint regression analysis was performed to identify a statistically significant time point of a change in trend. RESULTS: No joinpoints around WAAW were identified in Japan, the United Kingdom, or the United States from 2015 to 2020 with RSVs of 'AMR', whereas increasing RSVs were noted worldwide in 2017 and 2020. Further, there were decreasing RSVs of 'antibiotics' in the first half of 2020, which could be due to the COVID-19 pandemic. The study results suggest that WAAW did little to improve public awareness of AMR in the selected countries despite its contribution worldwide. CONCLUSIONS: This study implies that we need to develop a more effective method to improve public awareness to fight against AMR.

DOI： 10.1016/j.ijid.2021.08.018

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In vitro effectiveness of biapenem against IMP-producing Enterobacteriaceae. International journal

Kazuyoshi Gotoh, Makoto Miyoshi, I Putu Bayu Mayura, Koji Iio, Osamu Matsushita, Fumio Otsuka, Hideharu Hagiya

Journal of medical microbiology   70 ( 10 )   2021.10

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The options available for treating infections with carbapenemase-producing Enterobacteriaceae (CPE) are limited; with the increasing threat of these infections, new treatments are urgently needed. Biapenem (BIPM) is a carbapenem, and limited data confirming its in vitro killing effect against CPE are available. In this study, we examined the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) of BIPM for 14 IMP-1-producing Enterobacteriaceae strains isolated from the Okayama region in Japan. The MICs against almost all the isolates were lower than 0.5 µg ml-1, indicating susceptibility to BIPM, while approximately half of the isolates were confirmed to be bacteriostatic to BIPM. However, initial killing to a 99.9 % reduction was observed in seven out of eight strains in a time-kill assay. Despite the small data set, we concluded that the in vitro efficacy of BIPM suggests that the drug could be a new therapeutic option against infection with IMP-producing CPE.

DOI： 10.1099/jmm.0.001430

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Clinical Characteristics of Japanese Patients Who Visited a COVID-19 Aftercare Clinic for Post-Acute Sequelae of COVID-19/Long COVID. International journal

Yuki Otsuka, Kazuki Tokumasu, Yasuhiro Nakano, Hiroyuki Honda, Yasue Sakurada, Naruhiko Sunada, Daisuke Omura, Kou Hasegawa, Hideharu Hagiya, Mikako Obika, Keigo Ueda, Hitomi Kataoka, Fumio Otsuka

Cureus   13 ( 10 )   e18568   2021.10

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Introduction The long-term clinical course, prognosis, and optimal management of symptoms and conditions after the acute phase of coronavirus disease 2019 (COVID-19) remain to be elucidated. The purpose of this study was to clarify the characteristics of patients referred to a COVID-19 aftercare (CAC) clinic established at a tertiary academic hospital in Japan. Methods This study was a descriptive case series study. All patients who visited the CAC clinic between February 15 and September 17 in 2021 were included. Patients' background, chief complaints, and clinical courses after the onset of COVID-19 were described. Results A total of 87 Japanese patients (median age, 40.0 years; interquartile range [IQR], 26.5-53.0 years; 52.9% women) were referred to the CAC clinic. The median interval between the onset of COVID-19 and the visit to the clinic was 79.0 (IQR, 52.5-112.0) days. Referral sources were hospitals (36 patients), clinics (47 patients), a local healthcare center (3 patients), and other (1 patient). The most common chief complaint was general fatigue (50.4%) followed by dysosmia (28.7%), dysgeusia (26.4%), hair loss (18.4%), headache (17.2%), dyspnea (16.1%), and dyssomnia (13.1%). Respiratory symptoms were common in the early stages of the disease but were less common as the chief complaints when visiting the clinic. On the other hand, neurological, psychiatric, and extremity symptoms were predominant one month after the onset of COVID-19. Conclusions Regardless of the severity in the acute phase, patients visiting our CAC clinic suffered from a variety of symptoms. General physicians skilled in using a comprehensive approach would be optimal to see patients with such complex symptoms.

DOI： 10.7759/cureus.18568

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COVID-19外国人入院診療の実際

大塚 勇輝, 萩谷 英大, 中野 靖浩, 大村 大輔, 長谷川 功, 大塚 文男

日本医師会雑誌   150 ( 7 )   1237 - 1241   2021.10

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国際化を背景に、在日外国人も新型コロナウイルス感染症(COVID-19)に罹患しているが、本邦でその診療上の課題に関する文献はない。2020年2月からの1年間に岡山大学病院総合内科・総合診療科に入院した、外国人COVID-19患者全5人を対象として、患者背景や言語状況、入院中のトラブルや解決策について診療録から抽出した。全員が日本語の書字・読字が全く不能であり、うち1人は日常会話も困難で電話医療通訳サービスを要したが、担当医や看護師に加えて、国際診療支援センターや臨床栄養部、精神科などと連携することで隔離解除まで入院継続が可能であった。COVID-19では本人の希望に沿わない入院や予定外入院のため、通常の外国人診療に比して負担・課題が大きい。特に言語面での制約は、隔離管理下での意思疎通や同意書の取得などの面で障壁となることが明らかとなった。院内組織の連携と、病院を超えた情報共有による病軟な対応が重要である。(著者抄録)

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COVID-19後の後遺症が診断の契機となったLOH症候群の1例

副島 佳晃, 中野 靖浩, 徳増 一樹, 大塚 勇輝, 櫻田 泰江, 本多 寛之, 中本 健太, 長谷川 功, 萩谷 英大, 植田 圭吾, 大塚 文男

日本内分泌学会雑誌   97 ( 2 )   496 - 496   2021.10

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炎症性動脈瘤を合併し仮面尿崩症を呈した下垂体機能低下症の1例

平 佑貴, 中野 靖浩, 中本 健太, 庵谷 紘美, 長谷川 功, 萩谷 英大, 三好 智子, 大塚 文男

日本内分泌学会雑誌   97 ( 2 )   491 - 491   2021.10

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虹彩炎が治療導入の契機となった2型糖尿病の1例

中本 健太, 本多 寛之, 平 佑貴, 庵谷 紘美, 中野 靖浩, 長谷川 功, 萩谷 英大, 小比賀 美香子, 片岡 仁美, 大塚 文男

日本内分泌学会雑誌   97 ( 2 )   555 - 555   2021.10

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COVID-19肺炎を発症した高Ca血症・肺病変を伴うMEN1の1例

大塚 勇輝, 田中 秀一, 本多 寛之, 長谷川 功, 萩谷 英大, 小松原 基志, 岸田 雅之, 大塚 文男

日本内分泌学会雑誌   97 ( 2 )   548 - 548   2021.10

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高用量ステロイド治療が奏功した重症COVID-19妊婦の1例

山本 紘一郎, 萩谷 英大, 牧 尉太, 岡原 修司, 長谷川 功, 大塚 文男

日本内分泌学会雑誌   97 ( 2 )   568 - 568   2021.10

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総合診療におけるカテコールアミン測定の有用性とその解釈

砂田 匠彦, 花山 宜久, 灘 隆宏, 徳増 一樹, 山本 紘一郎, 中野 靖浩, 長谷川 功, 萩谷 英大, 小比賀 美香子, 大塚 文男

日本内分泌学会雑誌   97 ( 2 )   560 - 560   2021.10

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Gender-Dependent Characteristics of Serum 1,25-Dihydroxyvitamin D/25-Hydroxyvitamin D Ratio for the Assessment of Bone Metabolism. International journal

Manami Fujita-Yamashita, Koichiro Yamamoto, Hiroyuki Honda, Yoshihisa Hanayama, Kazuki Tokumasu, Yasuhiro Nakano, Kou Hasegawa, Hideharu Hagiya, Mikako Obika, Hiroko Ogawa, Fumio Otsuka

Cureus   13 ( 9 )   e18070   2021.9

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Objectives Vitamin D deficiency, which is common worldwide, increases the risks of falls and fractures and can lead to increased morbidity and mortality. However, the clinical utility and relevance of vitamin D activation remain unknown. The aim of the present study was to clarify the clinical usefulness of serum 1,25-dihydroxyvitamin D (1,25D)/25-hydroxyvitamin D (25D) ratio for assessment of the extent of bone metabolism. Methods We retrospectively screened data for 87 patients whose serum 1,25D and 25D levels were measured. Eight patients who were taking vitamin D preparations were excluded, and data for 79 patients (33 males and 46 females) were analyzed. Since menopausal status can be associated with serum vitamin D level, we divided the patients by gender and divided the female patients into two groups at the age of 50 years. Results The median serum 1,25D/25D ratio was significantly lower in males than in females, with the most considerable difference in all males [4.1 (interquartile range: 2.3-5.8) × 10-3] versus elderly females (aged ≧50 years) [7.9 (3.3-10.1) × 10-3). Main disorders were endocrine (30.6%), inflammatory (18.5%), and bone-related (16.7%) disorders. The ratios of serum 1,25D/25D had significant negative correlations with femoral dual-energy X-ray absorptiometry % young adult mean (DEXA %YAM) (R=-0.35) and lumbar DEXA %YAM (R=-0.32). Significant correlations were found between the 1,25D/25D ratio and serum levels of inorganic phosphate (iP), parathyroid hormone, and alkaline phosphatase (ALP). The 1,25D/25D ratio had gender-specific characteristics: the ratio was significantly correlated with age in males (R=-0.49), while it was significantly correlated with BMI in females (R=0.34). Conclusions The results of this study suggested that vitamin D activity is negatively correlated with bone mineral density, being reduced in aged males but enhanced in obese females.

DOI： 10.7759/cureus.18070

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Candidemia in COVID-19 treated with corticosteroids and tocilizumab. International journal

Koichiro Yamamoto, Kaoru Nakamura, Hideharu Hagiya, Fumio Otsuka

Clinical case reports   9 ( 9 )   e04858   2021.9

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COVID-19 patients treated with anti-inflammatory drugs are rarely complicated by candidemia. Since immunosuppressive therapy can blunt inflammatory reactions, clinicians should actively survey latent candidemia during severe COVID-19 treatment.

DOI： 10.1002/ccr3.4858

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High-Dose Corticosteroids for a Pregnant Woman Critically Ill With Coronavirus Disease 2019. International journal

Koichiro Yamamoto, Hideharu Hagiya, Jota Maki, Shuji Okahara, Kou Hasegawa, Fumio Otsuka

Cureus   13 ( 8 )   e17398   2021.8

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Pregnancy was reported to be a risk factor for coronavirus disease 2019 (COVID-19), with an increased risk for premature birth. Corticosteroids and remdesivir are used for patients with COVID-19; however, there is no established treatment for these patients. In particular, the effective management of pregnant, critically ill patients with COVID-19 remains unknown. We describe a 34-year-old, critically ill woman at 30 weeks of gestation with COVID-19, who was successfully treated with remdesivir and combined high-dose betamethasone (12 mg/day for two days) and methylprednisolone (125 mg/day for three days) followed by steroid tapering. During treatment, fetal biophysical profile scores on obstetric ultrasound were normal; her pregnancy course progressed well. Since high-dose corticosteroids improve fetal lung maturation and as well as cytokine storm due to COVID-19, this case provides an insight into the management of pregnant COVID-19 patients.

DOI： 10.7759/cureus.17398

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No Association Observed Between the Number of Infectious Disease Experts and Prevalence of Antimicrobial-Resistant Pathogens in Japan. International journal

Hideharu Hagiya, Fumio Otsuka

Cureus   13 ( 8 )   e16918   2021.8

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INTRODUCTION: The global spread of emerging infections has increased the demand for infectious disease (ID) experts. There is no established method to evaluate the sufficiency of professionals on a regional basis. We aimed to determine the correlation of the number of ID doctors and certified nurses in infection control (CNIC) with the prevalence of representative antimicrobial-resistant (AMR) pathogens across the 47 prefectures in Japan using publicly available databases. METHODS: We determined the number of ID doctors and CNIC registered in each prefecture based on the Japanese Association for Infectious Diseases and the Japanese Nursing Association websites and calculated their numbers per 100,000 population. Data on representative AMR pathogens were extracted from the Japan Nosocomial Infections Surveillance database. Spearman's correlation coefficient was used to measure statistical associations. RESULTS: There was no epidemiologically applicable correlation between the deployment of ID doctors and CNIC and the isolation rates of methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, cefotaxime- or levofloxacin-resistant Escherichia coli and Klebsiella pneumoinae, and meropenem-resistant Pseudomonas aeruginosa. Solely, the isolation rate of levofloxacin-resistant K. pneumoinae and the number of CNIC were statistically correlated (correlation coefficient = -0.33; p = 0.02), while the isolation rate of cefotaxime-resistant E. coli was paradoxically correlated with the number of ID doctors (correlation coefficient = 0.33; p = 0.02). Conclusions: Our macroscopic analysis using the open database was not a reliable method to evaluate the sufficiency of ID experts across the prefectures in Japan. A scheme to assess the appropriate distribution of ID experts should be developed.

DOI： 10.7759/cureus.16918

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An Elderly Male with Primary Sjögren's Syndrome Presenting Pleuritis as the Initial Manifestation.

Yukichika Yamamoto, Yuki Otsuka, Takayuki Katsuyama, Yoshito Nishimura, Kosuke Oka, Kou Hasegawa, Hideharu Hagiya, Fumio Otsuka

Acta medica Okayama   75 ( 4 )   539 - 542   2021.8

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Primary Sjögren's syndrome (SS) is an autoimmune disease that usually affects the exocrine glands in mid-dle-aged women. Fifteen percent of SS patients experience severe systemic extraglandular complications, and pleuritis is one of the rare complications of SS. We report the case of an elderly Japanese man who initially pre-sented with a prolonged fever and chest pain and was finally diagnosed with primary SS-associated pleuritis. Of the nine reported cases of primary SS that initially presented with pleuritis, up to six cases were elderly males. This case highlights the complication of pleuritis among elderly males with primary SS.

DOI： 10.18926/AMO/62409

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High-dose steroids for the treatment of severe COVID-19: comment. International journal

Shuichi Tanaka, Koichiro Yamamoto, Hideharu Hagiya, Kou Hasegawa, Fumio Otsuka

Internal and emergency medicine   16 ( 5 )   1415 - 1416   2021.8

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DOI： 10.1007/s11739-021-02766-0

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Ivermectin for Coronavirus Disease 2019: Yet to Be Well Evaluated Before Clinical Use. International journal

Hideharu Hagiya, Fumio Otsuka

Clinical therapeutics   43 ( 9 )   1622 - 1623   2021.7

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DOI： 10.1016/j.clinthera.2021.07.007

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Large-vessel vasculitis induced by granulocyte colony-stimulating factor administration after chemotherapy. International journal

Koichiro Yamamoto, Nayu Tamura, Kosuke Oka, Kou Hasegawa, Hideharu Hagiya, Madoka Hokama, Joji Ishida, Fumio Otsuka

Modern rheumatology case reports   5 ( 2 )   322 - 326   2021.7

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Granulocyte colony-stimulating factor (G-CSF) is a relatively new drug that is used for recovery of chemotherapy-associated neutropenia. It is known to cause bone pain, headache and fatigue as side-effects; however, large-vessel vasculitis is extremely rare and its relation with G-CSF remains unknown. We describe a 49-year-old woman in whom arteritis developed after chemotherapy and subsequent G-CSF administration. She had experienced pinealoma 3 months ago and received surgery and chemotherapy, leading to neutropenia. After administration of lenograstim at 100 μg/day for 1 week, high fever and neck pain appeared. White blood cell count and serum levels of C-reactive protein and interleukin-6 were increased to 37,930/μL, 23.71 mg/dL, and 241 pg/mL, respectively. Contrast-enhanced computed tomography revealed thickened walls of large vessels including the bilateral common carotid artery (CCA), right brachiocephalic artery, and ascending aorta. Ultrasonography showed wall thickening of the CCA (maximum of intima media thickness: right, 2.9 mm; left, 3.2 mm). As differential diagnoses, infection, chemotherapy, autoimmune diseases, and cancer were considered other than G-CSF. Blood culture tests, lumbar puncture, β-D-glucan tests, and tests for viral antibodies indicated no active infection, and autoantibodies were negative. Empirical antibiotic therapy was ineffective. The score of Naranjo's algorithm to lenograstim was 6, indicating "probable" causality. Considering the clinical course and test results, we made a diagnosis of G-CSF-associated arteritis and commenced glucocorticoid therapy, which drastically improved the symptoms and inflammation. Clinicians should be aware of this uncommon but significant complication of GCS-F administration, for which glucocorticoid treatment can be a useful therapeutic option.

DOI： 10.1080/24725625.2020.1857022

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Deployment of Infectious Disease Experts and Prevalence of Antimicrobial Resistance in Okayama: A Call for Training of Specialists. International journal

Hideharu Hagiya, Koji Fujita, Shinya Kamiyama, Kazuki Ocho, Haruto Yamada, Fumio Otsuka

Cureus   13 ( 7 )   e16643   2021.7

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Objective During the ongoing global pandemic of novel coronavirus disease 2019 (COVID-19), an emerging infectious disease, the implementation and execution of infection prevention and control (IPC) is of paramount importance. In this study, we aimed to assess the current deployment of infection control medical personnel in Okayama prefecture, who are supposed to play an essential role to prevent the outbreak of infectious diseases, and the current prevalence of antimicrobial-resistant (AMR) bacteria isolated in Okayama. Materials and methods This was a descriptive study using publicly available data. The numbers of infectious disease (ID)-doctors and the certified nurses in infection control (CNIC) per 100,000 population in 47 prefectures in Japan were calculated. We then compared the detected proportions of AMR pathogens among the prefectures in 2019 to be employed as a comparative parameter, which was obtained from Japan Nosocomial Infections Surveillance (JANIS) data. Results The number of ID-doctors was the 11th highest in Japan; however, they were unevenly distributed in southern Okayama, particularly at three tertiary hospitals. While the deployment of CNIC was geographically less uneven in the prefecture, their number was lower than the domestic average. According to the JANIS data, isolation rates of AMR pathogens were high in Okayama compared to other prefectures in Japan: vancomycin-resistant Enterococcus faecium (the third-worst); cefotaxime-resistant Escherichia coli and Klebsiella pneumoniae (the third-worst and the second-worst, respectively); and meropenem-resistant Pseudomonas aeruginosa (the worst). Conclusions Our assessment provides underlying data and reinforces the need for educating multi-professional experts in the field of infectious diseases to prevent future public health threats in Okayama.

DOI： 10.7759/cureus.16643

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A patient with human coronavirus NL63 falsely diagnosed with COVID-19; Lesson learned for the importance of definitive diagnosis. International journal

Yuki Otsuka, Hideharu Hagiya, Yasuhiro Nakano, Daisuke Omura, Kou Hasegawa, Haruto Yamada, Koji Iio, Tomoyuki Honda, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   27 ( 7 )   1126 - 1128   2021.7

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The gold standard for the diagnosis of coronavirus disease 2019 (COVID-19) is a nucleic acid detection test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may occasionally reveal false-positive or false-negative results. Herein, we describe a case of a patient infected with human coronavirus NL63 (HCoV-NL63) who was falsely diagnosed with COVID-19 using the Ampdirect™ 2019-nCoV detection kit (Shimadzu Corporation, Japan) and SARS-CoV-2 Detection Kit (TOYOBO co., ltd.), and was admitted to a COVID-19 hospital ward. We suspected a cross-reaction between HCoV-NL63 and SARS-CoV-2; however, the reported genome sequences of HCoV-NL63 and N1/N2 primers for SARS-CoV-2 do not correspond. Thus, the PCR result was supposed to be a false positive possibly due to contamination or human error. Although the issue of a false-negative result has been the focus of much attention to prevent the spread of the disease, a false positive is fraught with problems as well. Physicians should recognize that unnecessary isolation violates human rights and a careful diagnosis is indispensable when the results of laboratory testing for COVID-19 are unclear. Generally, in cases such as a duplicate PCR test was partially positive, either N1 or N2 alone was positive, PCR testing for two or more target regions resulted in a positive only for single region, a high cycle threshold >35 was obtained, a false positive should be suspected. Especially, when these conditions coincide, we should recognize the high likelihood of a false positive.

DOI： 10.1016/j.jiac.2021.05.001

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Barium appendicitis. International journal

Daisuke Omura, Naoko Yunoki, Yuki Otsuka, Yasuhiro Nakano, Hideharu Hagiya, Fumio Otsuka

Clinical case reports   9 ( 7 )   e04583   2021.7

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We have presented a case of barium appendicitis, which is a rare complication of barium enema studies. Barium sulfate is used widely for gastrointestinal radiographic studies and is associated with few complications. Clinicians need to be fully aware of this complication.

DOI： 10.1002/ccr3.4583

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Community spread and acquisition of clinically relevant Escherichia coli harbouring bla<inf>NDM</inf>among healthy Japanese residents of Yangon, Myanmar International journal

Yo Sugawara, Hideharu Hagiya, Yukihiro Akeda, Dan Takeuchi, Noriko Sakamoto, Yuki Matsumoto, Daisuke Motooka, Isao Nishi, Kazunori Tomono, Shigeyuki Hamada

Journal of Antimicrobial Chemotherapy   76 ( 6 )   1448 - 1454   2021.6

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Background: Carbapenemase-producing Enterobacterales (CPE) are spreading in hospitals, environment and retail foods in Yangon, Myanmar. Objectives: To investigate whether CPE colonize healthy individuals living in Yangon and whether clinical-related strains are spreading in the community. Methods: CPE was isolated from faecal samples obtained from healthy Japanese residents of Yangon with no history of hospitalization. Isolates were subjected to WGS using short- and long-read sequencers and compared with those previously isolated in Yangon. Results: Six Escherichia coli strains harbouring blaNDM-1 or blaNDM-5 belonging to five different STs - ST10, ST38, ST48, ST410 and ST8453 - were isolated from 69 volunteers. The ST38 isolates were related to those previously isolated from retail food in Yangon. The ST410 and ST8453 isolates were highly related to previous Yangon isolates including those of clinical and food origins. Conclusions: The analysis suggested the acquisition of blaNDM-positive E. coli, which are disseminating in a clinical setting and through retail foods, by healthy residents in Yangon.

DOI： 10.1093/jac/dkab070

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Interrelationships Between Serum Levels of Procalcitonin and Inflammatory Markers in Patients Who Visited a General Medicine Department

Jo Araki, Kosuke Oka, Koichiro Yamamoto, Yoshihisa Hanayama, Kazuki Tokumasu, Hideharu Hagiya, Hiroko Ogawa, Koichi Itoshima, Fumio Otsuka

ACTA MEDICA OKAYAMA   75 ( 3 )   299 - 306   2021.6

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Various laboratory markers of inflammation are utilized in general practice, but their clinical diagnostic significance is often ambiguous. In the present study, we determined the clinical significance of the examination of serum levels of procalcitonin (PCT) by comparing the PCT levels with the levels of other inflammatory markers, based on a retrospective review of 332 PCT-positive patients, including cases of bacterial infection (20.5%), non-specific inflammation (20.8%), neoplasm (9.9%), connective tissue diseases (8.4%), and non-bacterial infection (7.2%), were analyzed. The serum PCT level was highest in the bacterial infection group (1.94 ng/ml) followed by the non-specific inflammatory group (0.58 ng/ml) and neoplastic diseases group (0.34 ng/ml). The serum PCT level was positively correlated with serum levels of C-reactive protein (rho = 0.62), soluble interleukin-2 receptor (sIL-2R; rho = 0.69), and ferritin, the plasma level of D-dimer, and white blood cell count, and negatively correlated with the serum albumin level (rho = -0.52), hemoglobin concentration, and platelet count. The serum PCT level showed a stronger positive correlation with the serum sIL-2R level than the other biomarkers. The results suggest that an increased PCT level may indicate not only an infectious state but also a non-bacterial inflammatory condition in the diagnostic process in general practice.

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Interrelationships Between Serum Levels of Procalcitonin and Inflammatory Markers in Patients Who Visited a General Medicine Department.

Jo Araki, Kosuke Oka, Koichiro Yamamoto, Yoshihisa Hanayama, Kazuki Tokumasu, Hideharu Hagiya, Hiroko Ogawa, Koichi Itoshima, Fumio Otsuka

Acta medica Okayama   75 ( 3 )   299 - 306   2021.6

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Various laboratory markers of inflammation are utilized in general practice, but their clinical diagnostic significance is often ambiguous. In the present study, we determined the clinical significance of the examination of serum levels of procalcitonin (PCT) by comparing the PCT levels with the levels of other inflammatory markers, based on a retrospective review of 332 PCT-positive patients, including cases of bacterial infection (20.5%), non-specific inflammation (20.8%), neoplasm (9.9%), connective tissue diseases (8.4%), and non-bacterial infection (7.2%), were analyzed. The serum PCT level was highest in the bacterial infection group (1.94 ng/ml) followed by the non-specific inflammatory group (0.58 ng/ml) and neoplastic diseases group (0.34 ng/ml). The serum PCT level was positively correlated with serum levels of C-reactive protein (rho=0.62), soluble interleukin-2 receptor (sIL-2R; rho=0.69), and ferritin, the plasma level of D-dimer, and white blood cell count, and negatively correlated with the serum albumin level (rho=-0.52), hemoglobin concentration, and platelet count. The serum PCT level showed a stronger positive correlation with the serum sIL-2R level than the other biomarkers. The results suggest that an increased PCT level may indicate not only an infectious state but also a non-bacterial inflammatory condition in the diagnostic process in general practice.

DOI： 10.18926/AMO/62221

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Mortar Kidney.

Hideharu Hagiya, Ryosuke Takase, Chie Inoue, Osamu Sui

Internal medicine (Tokyo, Japan)   60 ( 9 )   1481 - 1481   2021.5

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DOI： 10.2169/internalmedicine.5314-20

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Population-Based Observational Study of Adverse Drug Event-Related Mortality in the Super-Aged Society of Japan. International journal

Tomoko Funahashi, Toshihiro Koyama, Hideharu Hagiya, Ko Harada, Syunya Iinuma, Soichiro Ushio, Yoshito Zamami, Takahiro Niimura, Kazuaki Shinomiya, Keisuke Ishizawa, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu R Kano

Drug safety   44 ( 5 )   531 - 539   2021.5

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INTRODUCTION: Adverse drug events (ADEs) are a major cause of mortality. OBJECTIVE: We examined long-term trends for ADE-related deaths in Japan. METHODS: This observational study was conducted using the Japanese Vital Statistics from 1999 to 2016. Data for all ADE-related deaths were extracted using International Classification of Diseases, Tenth Revision codes. We analysed ADE-related deaths by age and sex and calculated crude and age-standardised mortality rates (ASMR) per 100,000 people. We used Joinpoint regression analysis to identify significant changing points in mortality trends and to estimate annual percentage change (APC). RESULTS: In total, 16,417 ADE-related deaths were identified. The crude mortality rate for individuals aged ≥ 65 years was higher than that of young individuals. The ASMR per 100,000 people increased from 0.44 in 1999 to 0.64 in 2016. The crude mortality rate increased from 0.44 in 1999 to 1.01 in 2016. The APC of ASMR increased at a rate of 2.8% (95% confidence interval [CI] 1.4-4.2) throughout the study period. In addition, crude mortality increased at a rate of 5.7% (95% CI 4.2-7.3) annually from 1999 to 2016. The ADE-related mortality rate was higher for men than for women during the study period. CONCLUSIONS: The number of and trend in ADE-related deaths increased in Japan from 1999 to 2016, particularly in the older population.

DOI： 10.1007/s40264-020-01037-9

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HIV-associated cerebral lymphoma in an elderly patient.

Yuki Otsuka, Hideharu Hagiya, Yasuhiro Nakano, Ryu Kimura, Kentaro Fujii, Fumio Otsuka

Geriatrics & gerontology international   21 ( 5 )   435 - 436   2021.5

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DOI： 10.1111/ggi.14159

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Droopy eyelid due to IgG4-related dacryoadenitis. International journal

Ryosuke Takase, Hideharu Hagiya, Kazuki Tokumasu, Yoshito Nishimura, Atsunobu Sakurai, Kou Hasegawa, Yoshihisa Hanayama, Fumio Otsuka

Postgraduate medical journal   97 ( 1147 )   333 - 334   2021.5

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DOI： 10.1136/postgradmedj-2020-138416

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10-Year survey on serum antibody positivity rates and titers for measles and rubella in healthcare workers; an observational study at a Japanese university hospital. International journal

Nori Yoshioka, Matsuo Deguchi, Hideharu Hagiya, Masanori Kagita, Hiroko Tsukamoto, Miyuki Takao, Hisao Yoshida, Shigeto Hamaguchi, Ikuhiro Maeda, Yoh Hidaka, Kazunori Tomono

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   27 ( 9 )   1295 - 1299   2021.4

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BACKGROUND: We evaluated the effect of the two-dose vaccination strategy, which has been a widely adopted as childhood routine schedule worldwide to acquire herd immunity, on healthcare workers (HCWs) in Japan. METHODS: Between 2010 and 2019, antibody titers for measles and rubella were measured annually among newly employed HCWs at Osaka University Hospital, Japan, using Enzygnost® assays (Siemens Healthcare Diagnostics Co. Ltd., Marburg, Germany). The data were categorized by age to compare the antibody positivity rates and antibody titers among no-vaccine, single-dose, and two-dose groups. RESULTS: Over the 10-year period, the annual antibody positivity rates for measles and rubella were 84.0%-95.3% and 90.0%-94.5%, respectively, without any particular trend. The antibody titers for measles (median [interquartile range]: 8.4 [3.9, 20] vs. 6.1 [3.5, 12]) and rubella (11 [5.5, 20] vs. 6 [3.7, 11]) were statistically lower (p < 0.001) in the two-dose generation than in the single-dose generation. DISCUSSION: A shift from single-dose to two-dose vaccination did not yield an increase in antibody positivity rates for both measles and rubella among HCWs. Notably, antibody titers were significantly lower in the two-dose generation. CONCLUSION: Despite several limitations, our data suggests a paradoxical vulnerability in young HCWs who received the two-dose vaccination in a view of sero-positivity rates.

DOI： 10.1016/j.jiac.2021.04.006

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Trends in hepatitis C virus-associated mortality rates in Japan, 1998-2017. International journal

Hideharu Hagiya, Toshihiro Koyama, Matsuo Deguchi, Yusuke Minato, Satomi Miura, Tomoko Funahashi, Yusuke Teratani, Yoshito Zamami, Kazuaki Shinomiya, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu Kano

Journal of gastroenterology and hepatology   36 ( 9 )   2486 - 2492   2021.4

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BACKGROUND AND AIM: The current prevalence of hepatitis C virus infection and hepatitis C virus-associated mortality in Japan falls short of the World Health Organization goal of viral hepatitis elimination by 2030. We aimed to evaluate the trends in hepatitis C virus-associated mortality in Japan. METHODS: This nationwide observational study used the Japanese Vital Statistics from 1998 to 2017 and included all Japanese hepatitis C virus-associated deaths (84 936) of adults aged ≥ 40 years. We calculated the crude and age-standardized mortality rates per 100 000 persons by age and sex. Joinpoint regression analysis was used to identify significant changing points in trends and to estimate the annual percentage changes and the average annual percentage changes for the entire study period. RESULTS: The crude mortality rate per 100 000 persons (annual death number) increased from 5.5 (3548) in 1998 to 7.0 (4843) in 2005 and decreased to 4.0 (3095) in 2017. By 2017, the crude mortality rates per 100 000 persons among men and women had dropped to 3.6 and 4.3, respectively. The age-standardized mortality rate was higher in women than in men. The average annual percentage change was -3.8% (95% confidence interval: -5.0 to -2.5). The declining trend was more rapid in men (-4.5%, 95% confidence interval: -5.3 to -3.6) than in women (-2.7%, 95% confidence interval: -3.8 to -1.6). CONCLUSIONS: Trends in hepatitis C virus-associated mortality rates have declined in an accelerating manner in Japan, especially among men.

DOI： 10.1111/jgh.15517

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Disseminated gonococcal infection in a Japanese man with complement 7 deficiency with compound heterozygous variants: A case report. International journal

Misaki Kageyama, Hideharu Hagiya, Yasutaka Ueda, Katsuki Ohtani, Yasuo Fukumori, Norimitsu Inoue, Nobutaka Wakamiya, Nanoka Yoneda, Keigo Kimura, Motonori Nagasawa, Futoshi Nakagami, Isao Nishi, Ken Sugimoto, Hiromi Rakugi

Medicine   100 ( 13 )   e25265   2021.4

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RATIONALE: Complement deficiency are known to be predisposed to disseminated gonococcal infection (DGI). We herein present a case of DGI involving a Japanese man who latently had a complement 7 deficiency with compound heterozygous variants. PATIENT CONCERNS: A previously healthy 51-year-old Japanese man complained of sudden-onset high fever. Physical examination revealed various skin lesions including red papules on his trunk and extremities, an impetigo-like pustule on left forearm, and tendinitis of his right forefinger. DIAGNOSIS: Blood culture testing detected gram-negative cocci, which was confirmed to be Neisseria gonorrhoeae based on mass spectrometry and a pathogen-specific PCR test. INTERVENTIONS: Screening tests for underlying immunocompromised factors uncovered that complement activities (CH50) was undetectable. With a suspicion of a congenital complement deficiency, genetic analysis revealed rare single nucleotide variants in complement 7 (C7), including c.281-1G>T and a novel variant c.1454C>T (p.A485V). CH50 was normally recovered by adding purified human C7 to the patient's serum, supporting that the patient has C7 deficiency with compound heterozygous variants. OUTCOMES: Under a diagnosis of DGI, the patient underwent an antibiotic treatment with cefotaxime for a week and was discharged without any sequela. LESSONS: DGI is a rare sexually-transmitted infection that potentially induces systemic complications. Complement immunity usually defeats N. gonorrhoeae and prevents the organism from causing DGI. This case highlighted the importance of suspecting a complement deficiency when a person develops DGI.

DOI： 10.1097/MD.0000000000025265

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Trends in the incidence and mortality of legionellosis in Japan: a nationwide observational study, 1999-2017. International journal

Shinnosuke Fukushima, Hideharu Hagiya, Yuki Otsuka, Toshihiro Koyama, Fumio Otsuka

Scientific reports   11 ( 1 )   7246 - 7246   2021.3

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This study examined temporal trend, seasonality, and geographical variations of legionellosis incidence and mortality in Japan. This nationwide observational study used the Japanese Vital Statistics and Infectious Diseases Weekly Report (1999-2017) data to calculate legionellosis crude and age-adjusted incidence and mortality rates per 100,000 population by age and sex. Incidence was compared among the 4 seasons and regional incidence among 47 prefectures. Of 13,613 (11,194 men) people with legionellosis in Japan, 725 (569 men) were fatal. Increasing incidence trend occurred from 0.0004 (1999) to 1.37 (2017) per 100,000 population. People aged ≥ 70 years accounted for 43.1% overall; men's age-adjusted incidence rate was consistently approximately five times higher than for women. Significantly higher incidence occurred in summer than in winter (p = 0.013). Geographically, highest incidence (≥ 2.0 per 100,000 population) occurred in Hokuriku District, with increasing trends in Hokkaido and middle-part of Japan. Estimated fatality rates decreased consistently at 5.9% (95% confidence interval: - 8.1, - 3.5) annually, from 1999 to 2017, with no trend change point. Increasing legionellosis incidence occurred in Japan during 1999-2017, with declining estimated fatality rates. In this aging society and warming world, disease clinical burden may further deteriorate in future due to increasing incidence trends.

DOI： 10.1038/s41598-021-86431-8

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Burnout of Healthcare Workers amid the COVID-19 Pandemic: A Japanese Cross-Sectional Survey. International journal

Yoshito Nishimura, Tomoko Miyoshi, Hideharu Hagiya, Yoshinori Kosaki, Fumio Otsuka

International journal of environmental research and public health   18 ( 5 )   2021.3

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The coronavirus disease 2019 (COVID-19) global pandemic has drastically changed how we live and work. Amid the prolonged pandemic, burnout of the frontline healthcare professionals has become a significant concern. We conducted a cross-sectional survey study to provide data about the relationship between the COVID-19 pandemic and the prevalence of burnout in healthcare professionals in Japan. Healthcare workers in a single Japanese national university hospital participated in the survey, including basic demographics, whether a participant engaged in care of COVID-19 patients in the past 2 weeks and the Maslach Burnout Inventory. Of those, 25.4% fully answered the survey; 33.3% were doctors and 63.6% were nurses, and 36.3% engaged in care of COVID-19 patients in the past 2 weeks. Compared to those belonging to General Medicine, those in Emergency Intensive Care Unit were at higher risk of burnout (odds ratio (OR), 6.7; 95% CI, 1.1-42.1; p = 0.031). Of those who engaged in care of COVID-19 patients, 50% reported burnout while 6.1% did not (OR 8.5, 95% CI; 1.3-54.1; p = 0.014). The burnout of healthcare workers is a significant concern amid the pandemic, which needs to be addressed for sustainable healthcare delivery.

DOI： 10.3390/ijerph18052434

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Multiplex Real-Time PCR Assay for Six Major Carbapenemase Genes. International journal

Nori Yoshioka, Hideharu Hagiya, Matsuo Deguchi, Shigeto Hamaguchi, Masanori Kagita, Isao Nishi, Yukihiro Akeda, Kazunori Tomono

Pathogens (Basel, Switzerland)   10 ( 3 )   2021.3

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The global dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is a major concern in public health. Due to the existence of the diversity of carbapenemases, development of an easily available, cost-effective multiplex detection assay for CPE is required worldwide. Using clinically available and reliable equipment, COBAS® z480 (Roche Diagnostics K.K., Tokyo, Japan), we developed a multiplex real-time PCR assay for the detection of two combinations of carbapenemases; first, blaNDM, blaKPC, and blaIMP (Set 1), and second, blaGES, blaOXA-48, and blaVIM (Set 2). We constructed standard curves for each carbapenemase gene using serial dilutions of DNA standards, then applied reference or clinical isolates with each carbapenemase gene to this assay. The multiplex assay showed satisfactory accuracy to detect CPE genes, with the correlation coefficients of greater than 0.99 for all genotypes. The assay appropriately differentiated the reference or clinical strains harboring each carbapenemase gene without cross reactivity. Lastly, the assay successfully detected multiple genes without false-positive reactions by applying six clinical isolates carrying both NDM and OXA-48-like carbapenemase genes. Major advantages of our assay include multiplicity, simple operation, robustness, and speed (1 h). We believe that the multiplex assay potentially contributes to early diagnosis of CPE with a diverse genetic background.

DOI： 10.3390/pathogens10030276

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Impact of the COVID-19 Pandemic on the Psychological Distress of Medical Students in Japan: Cross-sectional Survey Study. International journal

Yoshito Nishimura, Kanako Ochi, Kazuki Tokumasu, Mikako Obika, Hideharu Hagiya, Hitomi Kataoka, Fumio Otsuka

Journal of medical Internet research   23 ( 2 )   e25232   2021.2

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BACKGROUND: The COVID-19 pandemic has negatively affected medical education. However, little data are available about medical students' distress during the pandemic. OBJECTIVE: This study aimed to provide details on how medical students have been affected by the pandemic. METHODS: A cross-sectional study was conducted. A total of 717 medical students participated in the web-based survey. The survey included questions about how the participants' mental status had changed from before to after the Japanese nationwide state of emergency (SOE). RESULTS: Out of 717 medical students, 473 (66.0%) participated in the study. In total, 29.8% (141/473) of the students reported concerns about the shift toward online education, mostly because they thought online education would be ineffective compared with in-person learning. The participants' subjective mental health status significantly worsened after the SOE was lifted (P<.001). Those who had concerns about a shift toward online education had higher odds of having generalized anxiety and being depressed (odds ratio [OR] 1.97, 95% CI 1.19-3.28) as did those who said they would request food aid (OR 1.99, 95% CI 1.16-3.44) and mental health care resources (OR 3.56, 95% CI 2.07-6.15). CONCLUSIONS: Given our findings, the sudden shift to online education might have overwhelmed medical students. Thus, we recommend that educators inform learners that online learning is not inferior to in-person learning, which could attenuate potential depression and anxiety.

DOI： 10.2196/25232

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Positron emission tomography for the diagnosis of prosthetic heart valve endocarditis. International journal

Yuki Otsuka, Hideharu Hagiya, Kosuke Oka, Fumio Otsuka

BMJ case reports   14 ( 2 )   2021.2

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DOI： 10.1136/bcr-2021-241640

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Clinical Characteristics of Low Androgen Status in Males with Type 2 Diabetes Mellitus

Jun Hamahara, Hiroyuki Honda, Koichiro Yamamoto, Kazuki Tokumasu, Yoshihisa Hanayama, Hideharu Hagiya, Mikako Obika, Keigo Ueda, Masayuki Kishida, Fumio Otsuka

ACTA MEDICA OKAYAMA   75 ( 1 )   1 - 8   2021.2

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To determine the clinical characteristics of low androgen status in adult males with diabetes, we retrospectively analyzed the medical records of patients with type 2 diabetes mellitus in whom serum free testosterone (FT) levels were examined for 1 year. Among the 46 patients (56 +/- 1.5 years old), decreases in serum FT levels to <8.5 pg/ml (indicating the occurrence of late-onset hypogonadism [LOH]) were detected in 18 (39%). The percentages of patients with low FT levels were high in the >= 50 years age group (83%), the HbA1c <7% group (67%), and the 25 <= BMI < 30 kg/m(2) group (56%). The serum FT levels tended to decrease age-dependently. The level of HbA1c was significantly correlated with the Heinemann Aging Male Symptoms (AMS) score (R= 0.47). The low-FT group had decreased levels of hemoglobin. Of note, the serum FSH level (R = -0.32) was negatively correlated with the serum FT level, whereas the serum TSH level (R= 0.36) was positively correlated with the serum FT level. Collectively, these results revealed that many diabetic males may have low FT levels and that the AMS score is related to the HbA1c level. A slightly anemic condition, thyroid dysfunction, and obesity (class 1) might be involved in LOH in middle-aged diabetic males.

DOI： 10.18926/AMO/61424

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Septic pulmonary emboli caused by Tsukamurella inchonensis: A case report International journal

Kazuyoshi Gotoh, I. Putu Bayu Mayura, Hideharu Hagiya, Kyoichi Obata, Tatsuo Ogawa, Koji Iio, Takumi Fujimori, Fumio Otsuka, Osamu Matsushita

Journal of Infection and Chemotherapy   27 ( 2 )   369 - 372   2021.2

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The genus Tsukamurella is a fastidious, environmental organism that potentially causes various infections in humans. Due to the morphological and biochemical similarities to others pathogens, such as Gordona, Rhodococcus, Corynebacterium, Nocardia, and Mycobacterium, a molecular-based approach is indispensable to correctly identify them. Herein, we describe a case of Tsukamurella inchonensis bacteremia complicated with septic pulmonary emboli (SPE), which is the first in the literature. A 44-year-old Japanese woman diagnosed with tongue cancer had undergone partial tongue resection. While receiving chemotherapy and radiotherapy, she developed high fever. Chest computed tomography suggested multiple emboli at the bilateral, peripheral lungs, indicating SPE. Blood culture detected Gram-positive rods, to which matrix-assisted laser desorption/ionization-time of flight mass spectrometry failed to identify. Then, we attempted to characterize it by 16S rRNA sequence, which suggested the organism to be Tsukamurella species but resulted in low resonance of the species-level identification. Additionally, we employed a confidence gene targeting groEL, leading to 100% matching (753/753 bps) with T. inchonensis NCTC 10741 (GenBank accession no. LR131273.1), which has been incorrectly registered as wrong species name Tsukamurella paurometabola in the database. Under the diagnosis of T. inchonensis-associated SPE, we successfully treated the patient with imipenem/cilastatin administration for 4 weeks. Sequencing analysis of groEL was of great use in identifying the organism in this case. More clinical cases based on molecular diagnosis of the fastidious pathogens need to be accumulated to further understand the characteristics and appropriate treatment regimen.

DOI： 10.1016/j.jiac.2020.09.024

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De-escalation concept and MIC literacy among medical students and clinical residents. International journal

Hideharu Hagiya, Kazuki Tokumasu, Mikako Obika, Fumio Otsuka

Postgraduate medical journal   98 ( e3 )   e183-e184   2021.1

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DOI： 10.1136/postgradmedj-2020-139562

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Without a silhouette. International journal

Yosuke Sazumi, Kazuki Tokumasu, Hideharu Hagiya, Fumio Otsuka

Clinical case reports   9 ( 1 )   574 - 575   2021.1

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Primary effusion lymphoma (PEL) is a kind of malignant lymphoma that develops without a tumor mass. A fluid smear is of no use for the diagnosis of miscellaneous condition. Repeated cell-block smear with immunostaining is useful for the diagnosis of PEL.

DOI： 10.1002/ccr3.3469

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Characterization of bla<inf>NDM-5</inf>-harbouring Klebsiella pneumoniae sequence type 11 international high-risk clones isolated from clinical samples in Yangon General Hospital, a tertiary-care hospital in Myanmar International journal

Yo Sugawara, Yukihiro Akeda, Hideharu Hagiya, Khwar Nyo Zin, Mya Mya Aye, Dan Takeuchi, Yuki Matsumoto, Daisuke Motooka, Isao Nishi, Kazunori Tomono, Shigeyuki Hamada

Journal of Medical Microbiology   70 ( 5 )   2021

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Fifteen Klebsiella pneumoniae isolates harbouring blaNDM genes were identified from blood and sputum specimens of patients at a tertiary-care facility (Yangon General Hospital, Yangon, Myanmar) in 2018. Two of the isolates belonged to sequence type (ST) 11, an international high-risk clone. Whole-genome sequencing and phylogenetic analyses revealed that these two isolates were clustered together with other ST11 isolates originating from other countries. The isolates harboured the blaNDM-5 gene on an IncFII-type plasmid that is prevalent among carbapenemase-producing Enterobacteriaceae in Yangon but has rarely been found in other ST11 isolates. Our data suggests the regional presence of the ST11 international high-risk clone and its acquisition of an endemic blaNDM-5-carrying plasmid.

DOI： 10.1099/JMM.0.001348

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Clinical Manifestations of Patients with Influenza Differ by Age : A Prospective, Multi-centered Study in the Setouchi Marine Area.

Ryosuke Takase, Hideharu Hagiya, Hiroyuki Honda, Yasuhiro Nakano, Hiroko Ogawa, Mikako Obika, Keigo Ueda, Hitomi Kataoka, Yoshihisa Hanayama, Fumio Otsuka

Acta medica Okayama   75 ( 5 )   567 - 574   2021

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Influenza potentially has a high mortality rate when it affects the elderly. We aimed to examine the differences in clinical manifestations in patients with influenza according to their age. This multicenter prospective study was performed in six medical institutions in Okayama and Kagawa prefectures (Japan). Between December 1, 2019 and March 31, 2020, we collected data on adult patients diagnosed with influenza type A, who were strat-ified into younger (20-49 years), middle-aged (50-64 years), and older groups (≥ 65 years). We compared the presence or absence of fever, respiratory symptoms, and extrapulmonary symptoms according to age group. In total, 203 patients (113, younger; 51, middle-aged; and 39, older) were eligible for the analysis. The maxi-mum body temperature and temperature at first physician visit in the older group were significantly lower than those in the younger group. The incidence of respiratory symptoms was not different among the three groups. Chills, muscle pain, and arthralgia as systemic symptoms were noted significantly more frequently in the younger (80.9%) and middle-aged (75.5%) groups than in the older group (51.3%) (p = 0.002). Fever and sys-temic symptoms were less likely to appear in older patients, possibly resulting in the delaying of hospital visits among older adults.

DOI： 10.18926/AMO/62769

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Antimicrobial prescription practices for outpatients with acute respiratory tract infections: A retrospective, multicenter, medical record-based study. International journal

Tomoharu Ishida, Hideharu Hagiya, Hiroyuki Honda, Yasuhiro Nakano, Hiroko Ogawa, Mikako Obika, Keigo Ueda, Hitomi Kataoka, Yoshihisa Hanayama, Fumio Otsuka

PloS one   16 ( 11 )   e0259633   2021

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Antimicrobial stewardship for outpatients with acute respiratory tract infections (ARTIs) should be urgently promoted in this era of antimicrobial resistance. Previous large-sample studies were based on administrative data and had limited reliability. We aimed to identify current antimicrobial prescription practices for ARTIs by directly basing on medical records. This multicenter retrospective study was performed from January to December in 2018, at five medical institutes in Japan. We targeted outpatients aged ≥18 years whose medical records revealed International Classification of Diseases (ICD-10) codes suggesting ARTIs. We divided the eligible cases into three age groups (18-64 years, 65-74 years, and ≥75 years). We defined broad-spectrum antimicrobials as third-generation cephalosporins, macrolides, fluoroquinolones, and faropenem. Primary and secondary outcomes were defined as the proportion of antimicrobial prescriptions for the common cold and other respiratory tract infections, respectively. Totally, data of 3,940 patients were collected. Of 2,914 patients with the common cold, 369 (12.7%) were prescribed antimicrobials. Overall, compared to patients aged ≥75 years (8.5%), those aged 18-64 years (16.6%) and those aged 65-74 years (12.1%) were frequently prescribed antimicrobials for the common cold (odds ratio [95% confidential interval]; 2.15 [1.64-2.82] and 1.49 [1.06-2.09], respectively). However, when limited to cases with a valid diagnosis of the common cold by incorporating clinical data, no statistical difference was observed among the age groups. Broad-spectrum antimicrobials accounted for 90.2% of the antimicrobials used for the common cold. Of 1,026 patients with other respiratory infections, 1,018 (99.2%) were bronchitis, of which antimicrobials were prescribed in 49.9% of the cases. Broad-spectrum antimicrobials were the main agents prescribed, accounting for nearly 90% of prescriptions in all age groups. Our data suggested a favorable practice of antimicrobial prescription for outpatients with ARTIs in terms of prescribing proportions, or quantitative aspect. However, the prescriptions were biased towards broad-spectrum antimicrobials, highlighting the need for further antimicrobial stewardship in the outpatient setting from a qualitative perspective.

DOI： 10.1371/journal.pone.0259633

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Acute encephalopathy associated with severe fever with thrombocytopaenia syndrome. International journal

Manami Fujita, Yasuhiro Nakano, Hiroyuki Honda, Hideharu Hagiya

BMJ case reports   13 ( 12 )   2020.12

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DOI： 10.1136/bcr-2020-240075

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Rheumatoid Meningoencephalitis.

Chie Inoue, Hideharu Hagiya, Yoshito Nishimura, Osamu Sui

Internal medicine (Tokyo, Japan)   59 ( 24 )   3255 - 3256   2020.12

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DOI： 10.2169/internalmedicine.5374-20

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Intra-arterial gas, a clue for diagnosis of peri-aortic inflammation due to infection. International journal

Daisuke Omura, Masatoshi Ogata, Yoshio Sakane, Ryuichi Matsuo, Harushige Nakatsukasa, Hideharu Hagiya, Fumio Otsuka

Clinical case reports   8 ( 12 )   3619 - 3620   2020.12

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We have presented a case of Salmonella-induced infective aortic aneurysm in which the presence of peri-aortic gas was a clue for diagnosis. The disease is clinically infrequent but potentially has a high mortality rate. Clinicians should consider this fatal disease from any trivial findings.

DOI： 10.1002/ccr3.3367

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Clinical Application of the Ratio of Serum Bone Isoform to Total Alkaline Phosphatase in General Practice.

Yuya Yokota, Yoshito Nishimura, Akemi Ando, Yoshihisa Hanayama, Kou Hasegawa, Hideharu Hagiya, Hiroko Ogawa, Mikako Obika, Keigo Ueda, Fumio Otsuka

Acta medica Okayama   74 ( 6 )   467 - 474   2020.12

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Alkaline phosphatase (ALP) is an enzyme that is expressed in a variety of tissues. Among the isoforms of ALP, bone-specific alkaline phosphatase (BAP) is used as a marker for evaluating bone metabolism. We investigated the clinical usefulness of the ratio of serum BAP to total ALP for the diagnosis of various disorders in general practice. We retrospectively analyzed the cases of 107 Japanese patients whose serum BAP levels were exam-ined, focusing on clinical characteristics. We observed that the BAP/ALP ratios of the patients with fever and those with inflammatory diseases were significantly lower than the ratios of other patient groups. The BAP/ALP ratios of the patients with osteoporosis and those with metabolic bone diseases were higher than those of the patients with other conditions. The BAP/ALP ratio was found to be negatively correlated with age, a cor-relation that has not been found in other ethnicities. The serum BAP/ALP ratio was inversely correlated with serum CRP levels but was positively correlated with serum albumin levels and hemoglobin concentrations. Collectively, our results suggest that the BAP/ALP ratio could be a useful predictor for important geriatric con-ditions seen in general practice.

DOI： 10.18926/AMO/61205

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Comparison of the Clinico-Microbiological Characteristics of Culture-Positive and Culture-Negative Septic Pulmonary Embolism: A 10-Year Retrospective Study. International journal

Yoshito Nishimura, Hideharu Hagiya, Mikako Obika, Fumio Otsuka

Pathogens (Basel, Switzerland)   9 ( 12 )   2020.11

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Septic pulmonary embolism (SPE) is a rare yet serious infectious disorder with nonspecific clinical findings due to microorganism-containing emboli disseminating from extrapulmonary infectious foci. It is unknown whether a positive blood culture correlates with a worse clinical outcome. We compared the clinical and microbiologic characteristics of patients with SPE divided into the culture-positive group and the culture-negative one. This study was a retrospective observational study of the patients diagnosed with SPE and treated in an academic hospital from April 2010 to May 2020. We identified six culture-positive and four culture-negative patients with SPE during the study period. The culture-positive group had significantly longer periods of hospitalization (median: 75 days, range: 45-125 days) than the culture-negative group (median: 14.5 days, range: 3-43 days) (p < 0.05), as well as significantly elevated serum C-reactive protein and procalcitonin. Patients with culture-negative SPE more commonly had odontogenic infections as the primary infectious foci. Our study highlights the importance of giving extra attention to SPE patients who have a positive blood culture, as they may have worse clinical outcomes. Physicians need to collaborate with dentists when faced with patients with culture-negative SPE, since they may have primary odontogenic infections.

DOI： 10.3390/pathogens9120995

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Massive pheochromocytoma. International journal

Terumitsu Anai, Kosuke Oka, Yuya Yokota, Yoshito Nishimura, Hideharu Hagiya, Fumio Otsuka

Clinical case reports   8 ( 11 )   2308 - 2309   2020.11

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Complications of pheochromocytoma, such as hypertensive emergency, can be critical. Clinicians should recognize that pheochromocytoma is not uncommon in patients with large adrenal tumors, and screening should be undertaken prior to any intervention.

DOI： 10.1002/ccr3.3124

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blaOXA -731 , a new chromosome-encoded blaOXA -48 -like variant in Shewanella sp. from the aquatic environment in Myanmar. International journal

Rathina Kumar Shanmugakani, Yo Sugawara, Yukihiro Akeda, Hideharu Hagiya, Noriko Sakamoto, Mya Mya Aye, Thuzar Myint, Shigeyuki Hamada, Kazunori Tomono

Environmental microbiology reports   12 ( 5 )   548 - 554   2020.10

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Shewanella sp., the progenitors of blaOXA-48 -like genes are increasingly reported with the possession of different blaOXA-48 -like variants. This study aims to characterize blaOXA-731 , a new variant of a blaOXA-48 -like gene identified in Shewanella sp. isolated from the aquatic environment in Myanmar. Phylogenetic analysis of the blaOXA-731 sequence with other blaOXA-48 -like variants showed that it has the highest nucleotide identity of 86.09% with blaOXA-48 . However, the active site motifs in OXA-731 were 100% identical to that in OXA-48. Whole-genome sequencing analysis showed that blaOXA-731 is not surrounded by any mobile genetic elements. The genetic context of blaOXA-731 was found as similar to other blaOXA-48 -like genes previously identified in Shewanella sp. S1 nuclease pulsed-field gel electrophoresis followed by Southern blotting confirmed the location of blaOXA-731 in the chromosome of the Shewanella genome. Cloning and expression studies showed that OXA-731 has β-lactamase activity similar to OXA-48 and OXA-181, but it has no significant carbapenemase activity. Our results showed the significance of blaOXA-48 -like-carrying Shewanella sp. in the spreading of blaOXA-48 -like genes in the community.

DOI： 10.1111/1758-2229.12875

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Disseminated Mycobacterium genavense infection mimicking TAFRO syndrome. International journal

Kosuke Oka, Mai Yamane, Yuya Yokota, Miho Yasuda, Kou Hasegawa, Takumi Fujimori, Koji Iio, Hideharu Hagiya, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   26 ( 10 )   1095 - 1099   2020.10

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TAFRO syndrome is a rare variant of idiopathic multicentric Castleman's disease, for which disseminated non-tuberculous mycobacteria (NTM) infection must be excluded. However, due to the slow and fastidious growth of the organisms, identification of the pathogen is often challenging. We herein describe a case of disseminated Mycobacterium genavence infection, in which manifestations of the patient were confusingly similar to those of TAFRO syndrome. A 69-year-old Japanese man presented with prolonged fever accompanying pain in his back and ribs on the right side. Systemic investigations revealed thrombocytopenia, marked elevation of alkaline phosphatase, anasarca (pleural effusion and ascites), megakaryocytosis in the bone marrow, and hepatomegaly. Magnetic resonance imaging (MRI) showed diffuse, T1-and T2-low-intensity spotted lesions on his vertebral bodies, but biopsy showed inconclusive results. The patient met the diagnostic criteria of TAFRO syndrome and was started on prednisolone, which improved his general condition shortly thereafter. Blood culture after 42 days of incubation revealed the presence of Mycobacterium; however, we considered it a contamination at that time because no organisms grew on conventional agars, and the patient was discharged. Ten weeks after the isolation of Mycobacterium, he developed persistent fever and was readmitted. This time, vertebral bone mallow biopsy demonstrated a large amount of mycobacterium, which was later successfully identified as M. genavense by sequencing analysis. Under a final diagnosis of disseminated M. genavense infection, we treated the patient with clarithromycin, rifampicin, and ethambutol. This case highlighted that disseminated NTM infection may follow a similar clinical course as that of TAFRO syndrome.

DOI： 10.1016/j.jiac.2020.06.020

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Concomitant vancomycin and piperacillin/tazobactam treatment is associated with an increased risk of acute kidney injury in Japanese patients. International journal

Yuto Haruki, Hideharu Hagiya, Mai Haruki, Yuta Inoue, Tetsuhiro Sugiyama

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   26 ( 10 )   1026 - 1032   2020.10

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INTRODUCTION: Recent studies have corroborated that the co-administration of vancomycin (VCM) and piperacillin/tazobactam (PT) is correlated with an increased incidence of acute kidney injury (AKI). However, evidence directed at the Japanese population is scarce. Therefore, we conducted a retrospective study to compare the occurrence of AKI among Japanese patients who received VCM with PT (VP therapy) and VCM with another β-lactams (VA therapy). METHODS: The present study, performed at Tsuyama Chuo Hospital between June 2012 and December 2018, included adult patients who received VCM and β-lactam antibiotics for ≥48 h. We defined the primary outcome as the incidence of AKI based on the risk, injury, failure, loss, and end-stage kidney disease criteria. Patients' clinical characteristics and outcomes were reviewed and compared between the two groups with univariate and multivariate logistic regression analyses. Subgroup analysis was conducted by stratifying the patients' baseline hospital admittance status, as intensive care unit or general wards. RESULTS: We analyzed 272 patients (92 V P therapy and 180 VA therapy). Univariate analysis revealed a significant difference in AKI development between VP and VA therapy (25.0% vs 12.2%; p < 0.01). A multivariate analysis demonstrated that VP therapy and VCM initial trough levels ≥15 μg/mL were associated with an incidence of AKI. Patients at general wards, rather than those admitted at an intensive care unit, developed AKI with VP therapy (p = 0.02). CONCLUSION: VP therapy was associated with an increased risk of AKI compared to that with VA therapy among the Japanese population.

DOI： 10.1016/j.jiac.2020.05.012

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Clinical Relevance of Serum Prolactin Levels to Inflammatory Reaction in Male Patients

Koichiro Yamamoto, Yoshihisa Hanayama, Kou Hasegawa, Kazuki Tokumasu, Tomoko Miyoshi, Hideharu Hagiya, Hiroko Ogawa, Mikako Obika, Koichi Itoshima, Fumio Otsuka

ACTA MEDICA OKAYAMA   74 ( 5 )   381 - 389   2020.10

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To clarify the relevance of prolactin (PRL) to clinical parameters in patients who visited our general medicine department, medical records of 353 patients in whom serum PRL levels were measured during the period from 2016 to 2018 were retrospectively reviewed. Data for 140 patients (M/F: 42/98) were analyzed after excluding patients lacking detailed records and patients taking dopaminergic agents. Median serum PRL levels were significantly lower in males than females: 6.5 ng/ml (IQR: 4.2-10.3) versus 8.1 ng/ml (5.9-12.9), respectively. Pain and general fatigue were the major symptoms at the first visit, and past histories of hypertension and dyslipidemia were frequent. Male patients with relatively high PRL levels (>= 10 ng/ml) had significantly lower levels of serum albumin and significantly higher levels of serum LDH than those with low PRL (< 10 ng/ml). There were significant correlations of male PRL level with the erythrocyte sedimentation rate (R=0.62), serum LDH level (R=0.39) and serum albumin level (R=-0.52), while the level of serum CRP (R=0.33) showed an insignificant but weak positive correlation with PRL level. Collectively, these results show that PRL levels had gender-specific relevance to various clinical factors, with PRL levels in males being significantly related to inflammatory status.

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Clinical Relevance of Serum Prolactin Levels to Inflammatory Reaction in Male Patients.

Koichiro Yamamoto, Yoshihisa Hanayama, Kou Hasegawa, Kazuki Tokumasu, Tomoko Miyoshi, Hideharu Hagiya, Hiroko Ogawa, Mikako Obika, Koichi Itoshima, Fumio Otsuka

Acta medica Okayama   74 ( 5 )   381 - 389   2020.10

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To clarify the relevance of prolactin (PRL) to clinical parameters in patients who visited our general medicine department, medical records of 353 patients in whom serum PRL levels were measured during the period from 2016 to 2018 were retrospectively reviewed. Data for 140 patients (M/F: 42/98) were analyzed after excluding patients lacking detailed records and patients taking dopaminergic agents. Median serum PRL levels were significantly lower in males than females: 6.5 ng/ml (IQR: 4.2-10.3) versus 8.1 ng/ml (5.9-12.9), respectively. Pain and general fatigue were the major symptoms at the first visit, and past histories of hypertension and dyslipidemia were frequent. Male patients with relatively high PRL levels (≥ 10 ng/ml) had significantly lower levels of serum albumin and significantly higher levels of serum LDH than those with low PRL (< 10 ng/ml). There were significant correlations of male PRL level with the erythrocyte sedimentation rate (R=0.62), serum LDH level (R=0.39) and serum albumin level (R=-0.52), while the level of serum CRP (R=0.33) showed an insignificant but weak positive correlation with PRL level. Collectively, these results show that PRL levels had gender-specific relevance to various clinical factors, with PRL levels in males being significantly related to inflammatory status.

DOI： 10.18926/AMO/60797

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Antibiotic literacy among Japanese medical students

Hideharu Hagiya, Hideo Ino, Kazuki Tokumasu, Hiroko Ogawa, Tomoko Miyoshi, Kanako Ochi, Fumio Otsuka

JOURNAL OF INFECTION AND CHEMOTHERAPY   26 ( 10 )   1107 - 1109   2020.10

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Antimicrobial resistance (AMR) is an urgent global issue. After the AMR action plan was introduced in 2016, a study on antibiotic literacy (i.e., awareness, knowledge, and attitude relating to antimicrobial use) among clinicians and lay people was conducted in Japan. However, no studies have hitherto targeted medical students who are expected to have a high level of antibiotic literacy. The present study was conducted between September 2019 and February 2020, enrolling undergraduate students at Okayama University Medical School. We collected data using a paper-based questionnaire form with 11 questions about antibiotic literacy. The response rate was 93.8% (661/705 students). Overall, 92.6% of the students knew that antibiotics inhibit the growth of bacteria. Student reporting that antibiotics could treat the common cold accounted for 77.0% (Year 1), 50.9% (Year 2), 48.2% (Year 3), 49.1% (Year 4), 23.8% (Year 5), and 26.2% (Year 6). Only 43 (6.5%) had heard about the AMR action plan. The study data suggested that medical students' level of literacy on antimicrobial use should be further enhanced to address AMR and promote antimicrobial stewardship. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2020.06.021

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Antibiotic literacy among Japanese medical students. International journal

Hideharu Hagiya, Hideo Ino, Kazuki Tokumasu, Hiroko Ogawa, Tomoko Miyoshi, Kanako Ochi, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   26 ( 10 )   1107 - 1109   2020.10

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Antimicrobial resistance (AMR) is an urgent global issue. After the AMR action plan was introduced in 2016, a study on antibiotic literacy (i.e., awareness, knowledge, and attitude relating to antimicrobial use) among clinicians and lay people was conducted in Japan. However, no studies have hitherto targeted medical students who are expected to have a high level of antibiotic literacy. The present study was conducted between September 2019 and February 2020, enrolling undergraduate students at Okayama University Medical School. We collected data using a paper-based questionnaire form with 11 questions about antibiotic literacy. The response rate was 93.8% (661/705 students). Overall, 92.6% of the students knew that antibiotics inhibit the growth of bacteria. Student reporting that antibiotics could treat the common cold accounted for 77.0% (Year 1), 50.9% (Year 2), 48.2% (Year 3), 49.1% (Year 4), 23.8% (Year 5), and 26.2% (Year 6). Only 43 (6.5%) had heard about the AMR action plan. The study data suggested that medical students' level of literacy on antimicrobial use should be further enhanced to address AMR and promote antimicrobial stewardship.

DOI： 10.1016/j.jiac.2020.06.021

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A nationwide trend analysis in the incidence and mortality of Creutzfeldt-Jakob disease in Japan between 2005 and 2014. International journal

Yoshito Nishimura, Ko Harada, Toshihiro Koyama, Hideharu Hagiya, Fumio Otsuka

Scientific reports   10 ( 1 )   15509 - 15509   2020.9

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In the era of hyper-ageing, Creutzfeldt-Jakob disease (CJD) can become more prevalent as an important cause of dementia. This study aimed to evaluate the trends in crude and age-adjusted CJD-associated mortality and incidence rates in Japan using national vital statistics data on CJD-associated deaths among individuals aged over 50 years, as well as the government-funded nationwide CJD surveillance data (pertaining to the years 2005-2014) in Japan. The data were analysed using the Joinpoint Regression Program to estimate the long-term trends and average annual percentage changes (AAPCs). Overall, the AAPCs of age-adjusted CJD-associated mortality rates rose significantly over the study period (3.2%; 95% confidence interval [CI] 1.4-5.1%). The AAPC of the age-adjusted incidence rates also increased (overall 6.4%; 95% CI 4.7-8.1%). The CJD-associated increases in the mortality and incidence rates were especially prominent among adults over the age of 70 years. Given this trend in aging of population, the disease burden of CJD will continue to increase in severity. Our findings thus recommend that policymakers be aware of the importance of CJD and focus on preparing to address the increasing prevalence of dementia.

DOI： 10.1038/s41598-020-72519-0

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Bilateral massive empyema with bronchopleural fistula. International journal

Ko Harada, Hideharu Hagiya, Fumio Otsuka

Postgraduate medical journal   96 ( 1139 )   573 - 573   2020.9

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DOI： 10.1136/postgradmedj-2019-137328

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Multiple Deep-seated Dentofacial Abscesses Caused by Multidrug-resistant Viridans Group Streptococci.

Shinnosuke Fukushima, Hideharu Hagiya, Yuki Mizuta, Yasuhiro Nakano, Masahiro Takahara, Kayo Okamoto, Yuko Hayashi, Kiyoshi Yamada, Kou Hasegawa, Fumio Otsuka

Internal medicine (Tokyo, Japan)   59 ( 16 )   2067 - 2070   2020.8

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Odontogenic infections, generally caused by dental caries and periodontal disease, can result in fatal illness. We herein report a 71-year-old Japanese woman with type 2 diabetes and hemodialysis who suffered from multiple dentofacial abscesses mainly caused by multidrug-resistant Streptococcus oralis. She complained of pain and swelling of her face, with an extraoral fistula from the left cheek. Following 3 surgical debridement procedures and partial mandibulectomy, in addition to 12 weeks of antimicrobial therapy, the multiple dentofacial abscesses were ameliorated. A combination of surgical and antimicrobial treatments following an early diagnosis is essential for reducing further complications.

DOI： 10.2169/internalmedicine.4283-20

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Mycobacterium chelonae bloodstream infection induced by osteomyelitis of toe: A case report International journal

Yayoi Ueda, Kazuki Tokumasu, Hideharu Hagiya, Koji Iio, Takumi Fujimori, Ayaka Kakehi, Mami Okura, Hiroshi Minabe, Fumio Otsuka

JOURNAL OF INFECTION AND CHEMOTHERAPY   26 ( 8 )   843 - 846   2020.8

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Mycobacterium chelonae is a rapidly growing mycobacterium that has the potential to cause refractory infections in humans. Mycobacteremia resulting from the organism is extremely rare, and its clinical features are yet to be uncovered. We herein present a case of M. chelonae bloodstream infection involving an immunocompromised older patient. A 79-year-old woman, on a long-term treatment with prednisolone plus tacrolimus for rheumatoid arthritis, visited our outpatient department complaining of deteriorating pain and swelling at her right 1st toe. Laboratory parameters showed elevated C-reactive protein and leukocytosis, and magnetic resonance imaging indicated osteomyelitis at the proximal phalanx of her right 1st toe. Considering the refractory course, the infected toe was immediately amputated. M. chelonae was isolated from bacterial cultures of the resected tissue and blood (BD BAC-TECT (TM) FX blood culture system, Becton Dickinson, Sparks, MD, USA), leading to a diagnosis of disseminated M. chelonae infection. We treated the patient with an antibiotic combination of clarithromycin, minocycline, and imipenem (2 weeks), which was converted to oral therapy of clarithromycin, doxycycline, and levofloxacin. This case highlighted the potential pathogenesis of M. chelonae to cause mycobacteremia in an immunocompromised patient. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2020.03.004

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Mycobacterium chelonae bloodstream infection induced by osteomyelitis of toe: A case report. International journal

Yayoi Ueda, Kazuki Tokumasu, Hideharu Hagiya, Koji Iio, Takumi Fujimori, Ayaka Kakehi, Mami Okura, Hiroshi Minabe, Fumio Otsuka

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   26 ( 8 )   843 - 846   2020.8

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Mycobacterium chelonae is a rapidly growing mycobacterium that has the potential to cause refractory infections in humans. Mycobacteremia resulting from the organism is extremely rare, and its clinical features are yet to be uncovered. We herein present a case of M. chelonae bloodstream infection involving an immunocompromised older patient. A 79-year-old woman, on a long-term treatment with prednisolone plus tacrolimus for rheumatoid arthritis, visited our outpatient department complaining of deteriorating pain and swelling at her right 1st toe. Laboratory parameters showed elevated C-reactive protein and leukocytosis, and magnetic resonance imaging indicated osteomyelitis at the proximal phalanx of her right 1st toe. Considering the refractory course, the infected toe was immediately amputated. M. chelonae was isolated from bacterial cultures of the resected tissue and blood (BD BACTEC™ FX blood culture system, Becton Dickinson, Sparks, MD, USA), leading to a diagnosis of disseminated M. chelonae infection. We treated the patient with an antibiotic combination of clarithromycin, minocycline, and imipenem (2 weeks), which was converted to oral therapy of clarithromycin, doxycycline, and levofloxacin. This case highlighted the potential pathogenesis of M. chelonae to cause mycobacteremia in an immunocompromised patient.

DOI： 10.1016/j.jiac.2020.03.004

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Invasive non-typeable Haemophilus influenzae infection due to endometritis associated with adenomyosis. International journal

Yoshito Nishimura, Hideharu Hagiya, Kaoru Kawano, Yuya Yokota, Kosuke Oka, Koji Iio, Kou Hasegawa, Mikako Obika, Tomoko Haruma, Sawako Ono, Hisashi Masuyama, Fumio Otsuka

BMC infectious diseases   20 ( 1 )   521 - 521   2020.7

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BACKGROUND: The widespread administration of the Haemophilus influenzae type b vaccine has led to the predominance of non-typable H. influenzae (NTHi). However, the occurrence of invasive NTHi infection based on gynecologic diseases is still rare. CASE PRESENTATION: A 51-year-old Japanese woman with a history of adenomyoma presented with fever. Blood cultures and a vaginal discharge culture were positive with NTHi. With the high uptake in the uterus with 67Ga scintigraphy, she was diagnosed with invasive NTHi infection. In addition to antibiotic administrations, a total hysterectomy was performed. The pathological analysis found microabscess formations in adenomyosis. CONCLUSIONS: Although NTHi bacteremia consequent to a microabscess in adenomyosis is rare, this case emphasizes the need to consider the uterus as a potential source of infection in patients with underlying gynecological diseases, including an invasive NTHi infection with no known primary focus.

DOI： 10.1186/s12879-020-05193-2

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Risk for the occupational infection by cytomegalovirus among health-care workers International journal

Miyuki Takao, Nori Yoshioka, Hideharu Hagiya, Matsuo Deguchi, Masanori Kagita, Hiroko Tsukamoto, Yoh Hidaka, Kazunori Tomono, Toru Tobe

Journal of Infection and Chemotherapy   26 ( 7 )   681 - 684   2020.7

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BACKGROUND: Cytomegalovirus (CMV) are ubiquitously distributed worldwide, causing a wide range of clinical manifestations from congenital infection to a life-threatening disease in immunocompromised individuals. CMV can be transmitted via human-to-human contact through body fluids; however, the risk of CMV infection among healthcare workers (HCWs) has not been fully evaluated. AIM: This study aimed to assess the risk of CMV infection among HCWs through daily medical practices. METHODS: Serum samples from HCWs at Osaka University Hospital (Japan) were analysed. Initially, we compared CMV IgG seropositivity among HCWs (medical doctors, nurses, and others) in 2017, which was examined after 1 year to evaluate seroconversion rates among those with seronegative results. Then, we examined CMV seroconversion rates in HCWs who were exposed to blood and body fluids. FINDINGS: We analysed 1153 samples of HCWs (386 medical doctors, 468 nurses, and 299 others), of which CMV seropositivity rates were not significantly different (68.9%, 70.3%, and 70.9%, respectively). Of these, 63.9% (221/346) of CMV seronegative HCWs were followed after 1 year, with CMV seroconversion rates of 3.2% (7/221). Among 72 HCWs who tested negative for CMV IgG when exposed to blood and body fluids, the CMV seroconversion rate was 2.8% (2/72). The CMV seroconversion rates between the two situations were not significantly different. CONCLUSION: Our study indicated that CMV infection through daily patient care seems quite rare. Further well-designed studies with a large sample size are warranted to verify our finding.

DOI： 10.1016/j.jiac.2020.02.011

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Trends in the nontuberculous mycobacterial disease mortality rate in Japan: A nationwide observational study, 1997-2016. Reviewed International journal

Ko Harada, Hideharu Hagiya, Tomoko Funahashi, Toshihiro Koyama, Mitsunobu R Kano, Fumio Otsuka

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America   73 ( 2 )   e321-e326   2020.6

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BACKGROUND: The incidence of nontuberculous mycobacterial (NTM) infections has been increasing worldwide, becoming a significant healthcare burden especially among elderly people. This study aimed to evaluate the trends in NTM-associated mortality in Japan. METHODS: This study used vital statistics data and data on all NTM-associated deaths (N=18,814) among individuals aged ≥40 years in Japan from 1997 to 2016. We calculated the crude and age-adjusted mortality rates by age and sex and used joinpoint regression to analyze trends and estimate the average annual percentage change (AAPC). We compared crude NTM- and tuberculosis (TB)-associated mortality rates by sex. RESULTS: The overall crude annual mortality rate increased from 0.63/100,000/year in 1997 to 1.93/100,000/year in 2016 and was the highest among individuals aged 80-84 years. The AAPC of the crude mortality rates among males of all ages and females aged 40-59 years were stable but increased among females aged 60-79 years (3.5%, 95% confidence interval [CI]: 2.8-4.3%) and ≥80 years (4.3%, 95% CI: 3.7-4.9%). Among males, the age-adjusted mortality rates did not show a significant trend, while among females, the rates increased over the study period (AAPC: 4.6%, 95% CI: 2.7-6.6%). In females, the crude NTM-associated mortality rate exceeded the TB mortality rate in 2014, 2015, and 2016. CONCLUSIONS:  NTM mortality increased in Japan between 1997 and 2016, especially among the elderly female population. Given the increasing NTM-associated mortality and susceptible aging population, public health authorities in Japan should pay greater attention to NTM infections.

DOI： 10.1093/cid/ciaa810

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Antibiotic prescriptions for Japanese outpatients with acute respiratory tract infections (2013-2015): A retrospective Observational Study. Reviewed International journal

Toshihiro Koyama, Hideharu Hagiya, Yusuke Teratani, Yasuhisa Tatebe, Ayako Ohshima, Mayu Adachi, Tomoko Funahashi, Yoshito Zamami, Hiroyoshi Y Tanaka, Ken Tasaka, Kazuaki Shinomiya, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu R Kano

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   26 ( 7 )   660 - 666   2020.3

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OBJECTIVES: Appropriate antibiotic prescriptions for outpatients with acute respiratory tract infections (ARTIs) are urgently needed in Japan. However, the empirical proof of this need is under-documented. Therefore, we aimed to determine antibiotic prescription rates, and the proportions of antibiotic classes prescribed for Japanese patients with ARTIs. METHODS: We analysed health insurance claims data over 2013-2015 among Japanese patients aged <75 years and determined the following indicators: 1) visit rates for patients with ARTIs and antibiotic prescription rates per 1000 person-years, and 2) proportion of visits by antibiotic-prescribed patients with ARTIs. We defined broad-spectrum antibiotics using the WHO Anatomical Therapeutic Chemical classification 4 level codes. RESULTS: Among 8.65 million visits due to ARTIs at 6859 hospitals and 62,024 physicians' offices, the visit rate and antibiotic prescription rate per 1000 person-years were 990.6 (99% confidence interval [CI], 989.4-991.7) and 532.4 (99% CI, 531.6-533.3), respectively. The visit rates for patients aged 0-17, 18-59, and 60-74 years were 2410.0 (99% CI, 2407.2-2412.9), 683.6 (99% CI, 682.7-684.6), and 682.1 (99% CI, 678.2-686.0), and antibiotic prescription rates were 1093.3 (99% CI, 1091.4-1095.2), 434.1 (99% CI, 433.4-434.9), and 353.4 (99% CI, 350.7-356.1), respectively. The overall proportion of antibiotic prescriptions for ARTI visits was 52.7% and 91.3% of the antibiotics prescribed were broad-spectrum. CONCLUSIONS: Both the visit rates and antibiotic prescription rates for ARTIs were high in this Japanese cohort. The proportion of antibiotic prescriptions exceeded that recommended in the clinical guidelines. Thus, there might be a scope for reducing the current antibiotic prescription rate in Japan.

DOI： 10.1016/j.jiac.2020.02.001

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Laryngeal Edema That Developed after Acute Myocardial Infarction. Reviewed

Futoshi Nakagami, Koichi Yamamoto, Hideharu Hagiya, Hiromi Rakugi

Internal medicine (Tokyo, Japan)   59 ( 5 )   759 - 760   2020.3

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DOI： 10.2169/internalmedicine.3507-19

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A nationwide observational study of mortality trends related to adverse drug reactions in Japan

船橋智子, 小山敏広, 萩谷英大, 原田洸, 寺谷祐亮, 座間味義人, 建部泰尚, 三上奈緒子, 大島礼子, 大島礼子, 四宮一昭, 北村佳久, 千堂年昭, 樋之津史郎, 狩野光伸

日本薬学会年会要旨集(CD-ROM)   140年会   28X - am11   2020.3

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Calciphylaxis of the fingers.

Ko Harada, Jo Araki, Kazuki Tokumasu, Hideharu Hagiya, Fumio Otsuka

Journal of general and family medicine   21 ( 2 )   25 - 26   2020.3

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A 69-year-old Japanese man with a 10-year history of hemodialysis for end-stage renal disease presented with painful necrosis of the fingers of his right hand. A plain radiograph of the right hand revealed severely calcified arteries, particularly in the ring finger, suggesting the diagnosis of calciphylaxis of the fingers.

DOI： 10.1002/jgf2.296

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Trends in Place of Death in a Super-Aged Society: A Population-Based Study, 1998-2017. Reviewed International journal

Toshihiro Koyama, Hideharu Hagiya, Tomoko Funahashi, Yoshito Zamami, Miyu Yamagishi, Hiroshi Onoue, Yusuke Teratani, Naoko Mikami, Kazuaki Shinomiya, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu R Kano

Journal of palliative medicine   23 ( 7 )   950 - 956   2020.2

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Background:
Globally, the number of deaths is estimated to increase to 74 million per year by 2030. Place of death (PoD) is increasingly being recognized as an important aspect of end-of-life care. However, recent trends in PoD in Japan, one of the super-aged societies, are unknown.
Objective:
To analyze trends in PoD in Japan over two decades.
Design:
Population-based retrospective observational study.
Setting:
All deaths reported in Japan, 1998-2017. PoD was defined as hospital, nursing home, or own home.
Results:
All Japanese decedents (∼22.6 million) over the past 20 years were analyzed. The proportion of hospital deaths was consistently high (>80%), with a significant decreasing trend from the mid-2000s. Although the proportion of deaths at home decreased in the first half of the study period, they later increased. There was a low proportion of deaths in nursing homes compared to other places of death; however, the proportion increased continually throughout the study period, particularly among women. In 2015, more women died in nursing homes than at home. Although the proportion of hospital deaths declined in the second half of the study period, their overall number continued to increase, reflecting an increase in total deaths in Japan.
Conclusions:
This study highlighted rapid changes in trends in PoD in Japan, and the need to consider affordable end-of-life care in Japan as well as other countries with aging populations. The findings from this long-term epidemiological study provide important insights on this issue.

DOI： 10.1089/jpm.2019.0445

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Repeated Chest Computed Tomography Revealed Early-stage Miliary Tuberculosis.

Hideo Okuno, Hideharu Hagiya, Shigeto Hamaguchi, Kazunori Tomono

Internal medicine (Tokyo, Japan)   59 ( 3 )   461 - 462   2020.2

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DOI： 10.2169/internalmedicine.3121-19

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Clinical Relevance of Blood Glucose and Gastroesophageal Reflux Symptoms to Depressive Status in Patients with Type 2 Diabetes Mellitus.

Hiroyuki Honda, Yoshihisa Hanayama, Mikako Obika, Kou Hasegawa, Jun Hamahara, Masayuki Kishida, Hideharu Hagiya, Hiroko Ogawa, Hitomi Kataoka, Fumio Otsuka

Acta medica Okayama   74 ( 1 )   33 - 40   2020.2

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A relationship between diabetes and depression is apparent. To clarify the clinical relevance of diabetic patients' gastroesophageal symptoms to their psychological status, we retrospectively analyzed the data from a Selfrating Depression Scale (SDS) and a Frequency Scale for Symptoms of Gastroesophageal reflux disease (FSSG) among 143 type 2 diabetic patients who visited a general medicine department. Among the 45 Japanese patients enrolled, the group with relatively high SDS scores (≥ 36) showed higher (FSSG) dysmotility symptom scores versus the low-SDS (< 36) group, although the 2 groups' characteristics and laboratory data were not significantly different. Positive correlations of postprandial plasma glucose (PPG) levels with FSSG scores (R=0.321, p<0.05), particularly with reflux scores (R=0.455, p<0.01) were revealed. PPG and HbA1c levels were not correlated with SDS scores. The patients' SDS scores were significantly correlated with their FSSG scores (R=0.41, p<0.01), suggesting that depressive status is linked to GERD-related manifestations. Considering that the patients' PPG levels were correlated with GERD-related symptoms, diabetic patients' blood glucose levels are associated with depressive status. Collectively, key symptoms related to GERD and glucose level values would be helpful.

DOI： 10.18926/AMO/57950

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In Vitro Efficacy of Meropenem-Cefmetazole Combination Therapy against New Delhi Metallo-β-lactamase-producing Enterobacteriaceae. Reviewed International journal

Hideharu Hagiya, Yo Sugawara, Yuko Tsutsumi, Yukihiro Akeda, Norihisa Yamamoto, Noriko Sakamoto, Rathina Kumar Shanmugakani, Ryuichiro Abe, Dan Takeuchi, Isao Nishi, Yoshikazu Ishii, Shigeyuki Hamada, Kazunori Tomono

International journal of antimicrobial agents   55 ( 3 )   105905 - 105905   2020.1

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BACKGROUND: Limited treatment options complicate management of infections with New Delhi metallo-β-lactamase (NDM)-producing organisms. We assessed the efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) against NDM-producing Enterobacteriaceae. MATERIALS AND METHODS: Twelve E. coli clinical isolates harbouring blaNDM-1 along with a positive control E. coli BAA-2469 harbouring blaNDM-1 were studied. Minimum inhibitory concentrations (MICs) of MEM, ertapenem (ERT), and CMZ were determined by broth microdilution. Checkerboard and time-kill assays were performed to confirm the in vitro efficacy of the MEM/CMZ combination. Scanning electron microscopy, kinetic studies, and whole genome sequence analysis were used to determine the antimicrobial resistant mechanisms. RESULTS: MICs of MEM, ERT, and CMZ in monotherapy ranged from 8 to 32, 16 to 128, and 32 to 512 μg/mL, respectively. In checkerboard, MEM/ERT resulted in no synergy, whereas MEM/CMZ showed a synergistic effect in all the tested isolates. Furthermore, the MIC of MEM in combination decreased by 2- to 8-fold compared to that of MEM alone. The time-kill study revealed a bactericidal effect in 4 out of 13 isolates at 24 hours. Scanning electron microscopy showed spheroidisation of the bacterial cell in the MEM/CMZ combination, which was not observed in single antibiotic conditions. The kinetic studies indicated a better activity of CMZ to ERT as an antagonist for NDM-1. Whole genome sequence analysis did not reveal any explainable differences between isolates susceptible to the combination therapy and those not susceptible to combination therapy. CONCLUSION: In vitro studies showed the potential effectiveness of MEM/CMZ combination therapy against NDM-producing organisms.

DOI： 10.1016/j.ijantimicag.2020.105905

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[Countermeasures for COVID-19 at Division of Radiology, Okayama University Hospital].

Toshi Matsushita, Ayako Ujifuku, Noriaki Akagi, Mitsugi Honda, Hideharu Hagiya, Susumu Kanazawa

Nihon Hoshasen Gijutsu Gakkai zasshi   76 ( 9 )   965 - 971   2020

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DOI： 10.6009/jjrt.2020_JSRT_76.9.965

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2020&ichushi_jid=J01192&link_issn=&doc_id=20200930490009&doc_link_id=130007906098&url=https%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007906098&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Place of death trends among patients with dementia in Japan: a population-based observational study. Reviewed International journal

Toshihiro Koyama, Misato Sasaki, Hideharu Hagiya, Yoshito Zamami, Tomoko Funahashi, Ayako Ohshima, Yasuhisa Tatebe, Naoko Mikami, Kazuaki Shinomiya, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu R Kano

Scientific reports   9 ( 1 )   20235 - 20235   2019.12

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Dementia is a major public health concern in ageing societies. Although the population of Japan is among the most aged worldwide, long-term trends in the place of death (PoD) among patients with dementia is unknown. In this Japanese nationwide observational study, we analysed trends in PoD using the data of patients with dementia who were aged ≥65 years and died during 1999-2016. Trends in the crude death rates and PoD frequencies were analysed using the Joinpoint regression model. Changes in these trends were assessed using the Joinpoint regression analysis in which significant change points, the annual percentage change (APC) and average APCs (AAPC) in hospitals, homes, or nursing homes were estimated. During 1999-2016, the number of deaths among patients with dementia increased from 3,235 to 23,757 (total: 182,000). A trend analysis revealed increased mortality rates, with an AAPC of 8.2% among men and 9.3% among women. Most patients with dementia died in the hospital, although the prevalence of hospital deaths decreased (AAPC: -1.0%). Moreover, the prevalence of nursing home deaths increased (AAPC: 5.6%), whereas the prevalence of home deaths decreased (AAPC: -5.8%). These findings support a reconsideration of the end-of-life care provided to patients with dementia.

DOI： 10.1038/s41598-019-56388-w

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Fall-related mortality trends in older Japanese adults aged ≥65 years: a nationwide observational study. Reviewed International journal

Hideharu Hagiya, Toshihiro Koyama, Yoshito Zamami, Yasuhisa Tatebe, Tomoko Funahashi, Kazuaki Shinomiya, Yoshihisa Kitamura, Shiro Hinotsu, Toshiaki Sendo, Hiromi Rakugi, Mitsunobu R Kano

BMJ open   9 ( 12 )   e033462   2019.12

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OBJECTIVES: Fall-related mortality among older adults is a major public health issue, especially for ageing societies. This study aimed to investigate current trends in fall-related mortality in Japan using nationwide population-based data covering 1997-2016. DESIGN: We analysed fall-related deaths among older persons aged ≥65 years using the data provided by the Japanese Ministry of Health, Labour and Welfare. RESULTS: The crude and age-standardised mortality rates were calculated per 100 000 persons by stratifying by age (65-74, 75-84 and ≥85 years) and sex. To identify trend changes, a joinpoint regression model was applied by estimating change points and annual percentage change (APC). The total number of fall-related deaths in Japan increased from 5872 in 1997 to 8030 in 2016, of which 78.8% involved persons aged ≥65 years. The younger population (65-74 years) showed continuous and faster-decreasing trends for both men and women. Average APC among men aged ≥75 years did not decrease. Among middle-aged and older women (75-84 and ≥85 years) decreasing trends were observed. Furthermore, the age-adjusted mortality rate of men was approximately twice that of women, and it showed a faster decrease for women. CONCLUSIONS: Although Japanese healthcare has shown improvement in preventing fall-related deaths over the last two decades, the crude mortality for those aged over 85 years remains high, indicating difficulty in reducing fall-related deaths in the super-aged population. Further investigations to uncover causal factors for falls in older populations are required.

DOI： 10.1136/bmjopen-2019-033462

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Bacteremia due to high-level daptomycin-resistant Corynebacterium striatum: A case report with genetic investigation. International journal

Hideharu Hagiya, Keigo Kimura, Hideo Okuno, Shigeto Hamaguchi, Daiichi Morii, Hisao Yoshida, Tomomi Mitsui, Isao Nishi, Kazunori Tomono

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   25 ( 11 )   906 - 908   2019.11

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Corynebacterium striatum, generally considered an opportunistic organism in humans, has recently been known to develop high-level daptomycin resistance (HLDR) shortly after drug exposure. To date, however, only several such clinical isolates have been described in the literature and clinical background of the resistant pathogen remains to be elucidated. Here, we report a case involving a C. striatum strain with HLDR harboring novel nucleotide mutations, together with a review of the relevant literature. To the best of our knowledge, this is the first well-investigated clinical report from Japan including a genetic investigation. Considering the rapid emergence of HLDR C. striatum in vitro experiment, there could be a number of underreporting cases. Scrupulous attention is required when administering daptomycin for the treatment of C. striatum infections, even if the organism has initially exhibited susceptibility.

DOI： 10.1016/j.jiac.2019.04.009

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Bactericidal efficacy of meropenem in combination with cefmetazole against IMP-producing carbapenem-resistant Enterobacteriaceae. Reviewed International journal

Abe R, Hagiya H, Akeda Y, Yamamoto N, Ishii Y, Tomono K

BMC research notes   12 ( 1 )   740 - 740   2019.11

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OBJECTIVE: Carbapenem-resistant Enterobacteriaceae (CRE) are among the most severe threats to public and clinical health because of their high levels of resistance to various antibiotics. We assessed the efficacy of combination therapy with meropenem (MEM) and cefmetazole (CMZ) against Imipenemase (IMP)-producing CRE, using the checkerboard method and time-killing assay on 13 Enterobacteriaceae isolates harboring blaIMP-1 (4 Enterobacter hormaechei, 5 Escherichia coli, and 4 Klebsiella pneumoniae isolates) and 13 isolates harboring blaIMP-6 (8 E. coli and 5 K. pneumoniae isolates). RESULTS: Minimum inhibitory concentrations (MICs) of MEM and CMZ ranged from 2 to 64 and 64 to 2048 μg/mL, respectively. Checkerboard method demonstrated the synergy of the MEM/CMZ combination in all the tested IMP-producing CRE isolates, and the time-kill assay indicated a bactericidal effect for both blaIMP-1 and blaIMP-6 positive CRE when MEM/CMZ combination was used. In vitro, the MEM/CMZ combination was potentially effective against IMP-1- or IMP-6-producing CRE. Further investigations including in vivo animal studies and clinical studies are warranted to corroborate the clinical utility of the novel combination therapy.

DOI： 10.1186/s13104-019-4779-x

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Human T-cell Leukemia Virus Type 2: Still Rare in Japan. International journal

Miyuki Takao, Nori Yoshioka, Hideharu Hagiya, Matsuo Deguchi, Masanori Kagita, Hiroko Tsukamoto, Yoh Hidaka, Kazunori Tomono, Toru Tobe

Clinical laboratory   65 ( 10 )   2019.10

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DOI： 10.7754/Clin.Lab.2019.190324

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A case of primary aldosteronism with resistant hypertension successfully treated by unilateral adrenalectomy after unsuccessful classification of subtype in adrenal venous sampling. Reviewed International journal

Nakamaru R, Yamamoto K, Nozato S, Hongyo K, Nagasawa M, Hagiya H, Nakagami F, Akasaka H, Kurinami H, Takami Y, Takeya Y, Sugimoto K, Ujike T, Uemura M, Nonomura N, Rakugi H

Clinical case reports   7 ( 10 )   1895 - 1899   2019.10

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Despite being an established method to identify the unilateral subtype of primary aldosteronism with an indication of adrenalectomy, adrenal venous sampling sometimes fails primarily due to unsuccessful cannulation to adrenal veins. In such cases, the analysis of clinical findings might help to identify the indication of surgery.

DOI： 10.1002/ccr3.2317

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Simultaneous and rapid detection method for measles and rubella using single-tube multiplex real-time quantitative RT-PCR. Reviewed International journal

Nori Yoshioka, Hideharu Hagiya, Matsuo Deguchi, Shigeto Hamaguchi, Masanori Kagita, Kazunori Tomono

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   25 ( 10 )   829 - 831   2019.10

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Patients with measles or rubella infections manifest acute onset fever accompanying systemic exanthema, which are clinically difficult to be distinguish. Rapid diagnosis and differentiation of such epidemic viral diseases is essential to prevent outbreaks. We developed a single-tube multiplex real-time PCR assay for these indistinguishable viruses. We used previously-reported primer settings, with a slight modification of reporter dye, and applied to multiplex Taqman real-time PCR by cobas z480 (Roche Molecular Systems, Inc.). Consequently, the assay could detect 10 copies/10 μl of measles and rubella with coefficient of variations of 11.2% and 21.8%, respectively. Strengths of our methodology include simplicity of operation, short measurement time (2 h), uses of internal control (confirming a run of PCR), and quantitative measurement with high sensitivity. Both measles and rubella currently cause social outbreaks in Japan. We hope that our single-tube multiplex assay contributes to an early diagnosis, leading to an appropriate infection control measure and prevention of epidemics.

DOI： 10.1016/j.jiac.2019.05.005.

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Dissemination of carbapenemase-producing Enterobacteriaceae harbouring blaNDM or blaIMI in local market foods of Yangon, Myanmar. International journal

Yo Sugawara, Hideharu Hagiya, Yukihiro Akeda, Mya Mya Aye, Hpoo Pwint Myo Win, Noriko Sakamoto, Rathina Kumar Shanmugakani, Dan Takeuchi, Isao Nishi, Akiko Ueda, Moh Moh Htun, Kazunori Tomono, Shigeyuki Hamada

Scientific reports   9 ( 1 )   14455 - 14455   2019.10

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The spread of carbapenemase-producing Enterobacteriaceae (CPE) poses a serious threat to clinical practice and public health. These bacteria are present both in clinical settings and non-clinical environments. The presence of CPE in food stuffs has been reported, but sporadically so. Here, we screened for CPE in meat, seafood, and vegetable samples from local markets of Yangon, Myanmar. We obtained 27 CPE isolates from 93 food samples and identified 13 as Escherichia coli, six as Klebsiella pneumoniae, seven as Enterobacter cloacae complex, and one as Serratia marcescens. All except the E. cloacae complex harboured the carbapenemase genes blaNDM-1 or blaNDM-5, while all Enterobacter isolates carried the carbapenemase gene blaIMI-1. The blaIMI-1 gene was located in putative mobile elements EcloIMEX-2, -3, or -8. Using multi-locus sequence typing, E. coli, K. pneumoniae, and E. cloacae complex isolates were classified into 10, six, and five different sequence types, respectively. Our results demonstrate that diverse organisms with various carbapenemase genes are widespread in the market foods in Yangon, highlighting the need for promoting proper food hygiene and effective measures to prevent further dissemination.

DOI： 10.1038/s41598-019-51002-5

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Association of Adverse Drug Events with Broad-spectrum Antibiotic Use in Hospitalized Patients: A Single-center Study.

Hideharu Hagiya, Ryohei Kokado, Akiko Ueda, Hideo Okuno, Daiichi Morii, Shigeto Hamaguchi, Norihisa Yamamoto, Hisao Yoshida, Kazunori Tomono

Internal medicine (Tokyo, Japan)   58 ( 18 )   2621 - 2625   2019.9

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Objective The importance of antimicrobial stewardship is increasingly highlighted in this age of antimicrobial resistance. A better comprehension of adverse drug events (ADEs) can promote the appropriate use of antibiotics. We aimed to quantify the incidence of ADEs associated with broad-spectrum systemic antibiotics in a hospital setting. Methods We conducted a six-month prospective, observational study at Osaka University Hospital to describe the incidence of ADEs in patients hospitalized in general wards undergoing treatment with broad-spectrum antibiotics [carbapenems, piperacillin/tazobactam (PIPC/TAZ), and anti-methicillin-resistant Staphylococcus aureus agents]. The occurrence of ADE was defined as any cardiac, gastrointestinal, hepatobiliary, renal, neurologic, hematologic, dermatologic, or musculoskeletal manifestation after 48 hours or more of systemic antibiotic therapy. Results The 3 most frequently prescribed antibiotics were PIPC/TAZ (242 cases), meropenem (181 cases), and vancomycin (92 cases). Of 689 patients, 118 (17.1%) experienced ADEs, including gastrointestinal (6.4%), hepatobiliary (4.2%), dermatologic (2.5%), and renal (2.3%) manifestations. Patients treated with PIPC/TAZ, meropenem, doripenem, vancomycin, daptomycin, and teicoplanin developed ADEs at rates of 20.7%, 16.0%, 15.4%, 19.6%, 11.8%, and 10.9%, respectively. Conclusion Our study provides a quantitative value for the incidence of ADEs associated with broad-spectrum antibiotics in clinical practice. To optimize patient safety, clinicians need to be aware of the risks associated with antibiotic administration.

DOI： 10.2169/internalmedicine.2603-18

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Case of Mycobacterium haemophilum infection presenting with Sweet's syndrome-like reactions. Reviewed International journal

Yuri Shimizu, Yukinobu Nakagawa, Yorihisa Kotobuki, Keigo Kimura, Hideharu Hagiya, Ichiro Katayama

The Journal of dermatology   46 ( 9 )   e319-e320 - e320   2019.9

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DOI： 10.1111/1346-8138.14864

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Pattern of antibiotic prescriptions for outpatients with acute respiratory tract infections in Japan, 2013-15: A retrospective observational study Reviewed International journal

Yusuke Teratani, Hideharu Hagiya, Toshihiro Koyama, Mayu Adachi, Ayako Ohshima, Yoshito Zamami, Hiroyoshi Y. Tanaka, Yasuhisa Tatebe, Ken Tasaka, Naoko Mikami, Kazuaki Shinomiya, Yoshihisa Kitamura, Mitsunobu R. Kano, Shiro Hinotsu, Toshiaki Sendo

Family Practice   36 ( 4 )   402 - 409   2019.8

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© 2018 The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Background: In this age of antimicrobial resistance, unnecessary use of antibiotics to treat non-bacterial acute respiratory tract infections (ARTIs) and inappropriate use of antibiotics in treating bacterial ARTIs are public health concerns. Purpose: Our aim is to identify the pattern of oral antibiotic prescriptions for outpatients with ARTIs in Japan. Methods: We analysed health insurance claims data of patients (aged ≤74 years) from 2013 to 2015, to determine the pattern of antibiotic prescriptions for outpatient ARTIs and calculated the proportion of each antibiotic. Results: Data on 4.6 million antibiotic prescriptions among 1559394 outpatients with ARTIs were analysed. The most commonly prescribed classes of antibiotics included cephalosporins (41.9%), macrolides (32.8%) and fluoroquinolones (14.7%). The proportion of first-, second- and third-generation cephalosporins was 1.0%, 1.7% and 97.3%, respectively. Fluoroquinolones accounted for a quarter of the prescriptions for ARTIs in patients aged >20 years. In contrast, penicillins accounted for just 8.0% of the total number of antibiotic prescriptions for ARTIs. Conclusions: According to clinical guidelines, penicillins are first-line antibiotics against ARTIs. However, third-generation cephalosporins, macrolides and fluoroquinolones are more frequently prescribed in Japan. Although we could not assess the extent to which appropriate antibiotics are selected, our results support the necessity of improving antibiotic choices in the treatment of ARTIs.

DOI： 10.1093/fampra/cmy094

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Mycobacterium kansasii arthritis of the elbow in an immunocompetent patient with a suspected soft-tissue tumor. Reviewed International journal

Okuno H, Tanaka H, Hagiya H, Yoshida H, Hamaguchi S, Hori Y, Morii E, Hamada K, Yoshikawa H, Tomono K

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   26 ( 2 )   261 - 264   2019.8

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Mycobacterium kansasii is one of the major non-tuberculous mycobacteria species that typically cause pulmonary diseases. M. kansasii is known to cause septic arthritis as an extrapulmonary disease in immunosuppressed patients or chronic skin disease. Herein, we present a case of M. kansasii arthritis involving the elbow of an immunocompetent patient, which was initially suspected to be a soft-tissue tumor. A 70-year-old man presented with a swollen left elbow that had progressed for 18 months with deteriorating arthralgia and limited range of motion. Magnetic resonance imaging revealed filling of the intra-articular space of the elbow and surrounding of the radial head with a soft tissue mass with mixed signal intensity. Initial incisional biopsy was performed via the lateral approach to the elbow joint, and pathological examination of the mass did not reveal any evidence of malignancy. One year after the first operation, arthroscopic surgery was performed to excise the mass following the recurrence of swelling and limited function of the elbow. Pathological examination of the resected synovium revealed epithelioid granulomas containing a multinucleated giant cell and inflammatory cell infiltration, characteristic of mycobacterial infection. M. kansasii was cultured after 2 weeks of incubation of the synovial sample. He experienced full resolution of the swelling and limited function following a combination of synovectomy and multidrug antimycobacterial treatment (rifampin 600 mg/day, clarithromycin 800 mg/day, and ethambutol 750 mg/day). This case highlights the need to consider this rare infection in the differential diagnosis of intra-articular soft tissue tumor-like lesions even in immunocompetent patients.

DOI： 10.1016/j.jiac.2019.07.015

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Pattern of antibiotic prescriptions for outpatients with acute respiratory tract infections in Japan, 2013-15: a retrospective observational study. Reviewed International journal

Yusuke Teratani, Hideharu Hagiya, Toshihiro Koyama, Mayu Adachi, Ayako Ohshima, Yoshito Zamami, Hiroyoshi Y Tanaka, Yasuhisa Tatebe, Ken Tasaka, Naoko Mikami, Kazuaki Shinomiya, Yoshihisa Kitamura, Mitsunobu R Kano, Shiro Hinotsu, Toshiaki Sendo

Family practice   36 ( 4 )   402 - 409   2019.7

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BACKGROUND: In this age of antimicrobial resistance, unnecessary use of antibiotics to treat non-bacterial acute respiratory tract infections (ARTIs) and inappropriate use of antibiotics in treating bacterial ARTIs are public health concerns. PURPOSE: Our aim is to identify the pattern of oral antibiotic prescriptions for outpatients with ARTIs in Japan. METHODS: We analysed health insurance claims data of patients (aged ≤74 years) from 2013 to 2015, to determine the pattern of antibiotic prescriptions for outpatient ARTIs and calculated the proportion of each antibiotic. RESULTS: Data on 4.6 million antibiotic prescriptions among 1559394 outpatients with ARTIs were analysed. The most commonly prescribed classes of antibiotics included cephalosporins (41.9%), macrolides (32.8%) and fluoroquinolones (14.7%). The proportion of first-, second- and third-generation cephalosporins was 1.0%, 1.7% and 97.3%, respectively. Fluoroquinolones accounted for a quarter of the prescriptions for ARTIs in patients aged >20 years. In contrast, penicillins accounted for just 8.0% of the total number of antibiotic prescriptions for ARTIs. CONCLUSIONS: According to clinical guidelines, penicillins are first-line antibiotics against ARTIs. However, third-generation cephalosporins, macrolides and fluoroquinolones are more frequently prescribed in Japan. Although we could not assess the extent to which appropriate antibiotics are selected, our results support the necessity of improving antibiotic choices in the treatment of ARTIs.

DOI： 10.1093/fampra/cmy094

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Clinical impact of extended blood culture examination: Too much of a good thing. Reviewed International journal

Hagiya H, Yoneda N, Kimura K, Mitsui T, Ueda A, Sunada A, Nishi I, Nakagami F, Rakugi H, Tomono K

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   25 ( 7 )   559 - 562   2019.7

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Blood culture is the most critical examination for diagnosing bacterial infections. The longer the blood culture incubation period, the higher the chances of identifying bacterial strains. However, unnecessary extension of the incubation period can burden the capacity of the instrument and merely result in the detection of contaminant bacteria having no clinical significance. This study aimed to optimize the blood culture incubation period using the currently available continuous-monitoring automated blood culture instrument. This was a 2-year retrospective study performed at Osaka University Hospital (January 1, 2016 to December 31, 2017). The BD BACTEC™ FX blood culture system (Becton Dickinson, Sparks, MD, USA) and BD BACTEC™ Plus series blood culture bottles were used. All blood cultures were incubated for more than 12 consecutive days. We reviewed the clinical data of cases that tested positive between 6 and 12 days of incubation. During the study period, 14,822 sets of blood culture were drawn. Of 1751 sets testing positive, 95.7% (1665 sets) became positive within 5 days of incubation. The overall contamination rate (false positives) after 6 days of incubation was 80.2% (69/86 sets). Based on the positive blood culture results, antimicrobials were changed in 7.0% (6/86) of the sets, and a diagnosis of infectious disease was made in only one case. There was no death associated with the extended blood culture results. In conclusion, the clinical impact of extended blood culture incubation for 6 days or more was limited, and a routine extension of the incubation period might be unnecessary.

DOI： 10.1016/j.jiac.2019.03.001

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In Vitro Effectiveness of Meropenem and Cefmetazole Combination Treatment Against KPC-2-Producing Enterobacteriaceae. Reviewed

Hagiya H, Aoki K, Akeda Y, Yamamoto N, Shanmugakani RK, Ishii Y, Tomono K

Microbial drug resistance (Larchmont, N.Y.)   25 ( 6 )   839 - 845   2019.7

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Pustules on the back possibly triggering toxic-shock syndrome. International journal

Hideharu Hagiya, Futoshi Nakagami, Yuki Minami, Hiroaki Terada

BMJ case reports   12 ( 6 )   2019.6

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We herein describe an irregular case of toxic-shock syndrome (TSS). A previously healthy 28-year-old Japanese man developed a sudden-onset high fever. The patient was suffering from conjunctival hyperaemia, gastrointestinal symptoms such as vomiting and diarrhoea, and systemically diffused macular erythroderma. Further physical examination detected pustules on his back, which self-destructed over time. Laboratory revealed multiple organ failures. Subsequently, scalded skin on the face and desquamation in the limb extremities emerged by day 10, leading to the diagnosis of TSS, despite his stable circulatory dynamics through the course. Learning points for clinicians include that they should recall TSS as a possible disease concurrently causing high fever, systemic rash and multiple organ dysfunctions, even without being in a state of shock. The characteristic desquamations emerged in the limb extremities after hospitalisation were of help in diagnosing TSS.

DOI： 10.1136/bcr-2019-229610

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A fatal case of Exophiala dermatitidis disseminated infection in an allogenic hematopoietic stem cell transplant recipient during micafungin therapy. Reviewed International journal

Hagiya H, Maeda T, Kusakabe S, Kawasaki K, Hori Y, Kimura K, Ueda A, Yoshioka N, Sunada A, Nishi I, Morii E, Kanakura Y, Tomono K

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   25 ( 6 )   463 - 466   2019.6

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Exophiala dermatitidis is a dematiaceous fungus that is increasingly becoming the cause of fungal infection in immunocompromised patients. However, the risk factors and optimal treatment modality for E. dermatitidis infection are unknown to date. Herein, we present a fatal case of E. dermatitidis infection in an adult patient that developed after allogeneic hematopoietic stem cell transplantation for chronic active Epstein-Barr virus infection. The dematiaceous fungus caused a breakthrough fungemia despite prophylactic administration of micafungin. Although the patient was intensively treated with liposomal-amphotericin B and voriconazole, serum level of beta-D-glucan continuously increased, and the patient eventually died because of cerebral hemorrhage. An autopsy found multiple involvements of the fungal infection at the bilateral lungs, thoracic cavities, diaphragm, and thyroid. To the best of our knowledge, this is the first reported case of E. dermatitidis infection involving these tissues as determined via autopsy. This case highlights the importance of attention for Exophiala infection in immunocompromised individuals in those given antifungal therapy with echinocandins.

DOI： 10.1016/j.jiac.2018.12.009

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Rapid screening and early precautions for carbapenem-resistant Acinetobacter baumannii carriers decreased nosocomial transmission in hospital settings: a quasi-experimental study. International journal

Norihisa Yamamoto, Shigeto Hamaguchi, Yukihiro Akeda, Pitak Santanirand, Narong Chaihongsa, Suntariya Sirichot, Suwichak Chiaranaicharoen, Hideharu Hagiya, Kouji Yamamoto, Anusak Kerdsin, Kazuhisa Okada, Hisao Yoshida, Shigeyuki Hamada, Kazunori Oishi, Kumthorn Malathum, Kazunori Tomono

Antimicrobial resistance and infection control   8   110 - 110   2019.6

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Background: Active surveillance has the potential to prevent nosocomial transmission of carbapenem-resistant Acinetobacter baumannii (CRAB). We assessed whether rapid diagnosis using clinical specimen-direct loop-mediated isothermal amplification (LAMP), a rapid molecular diagnostic assay, and subsequent intervention, could reduce CRAB nosocomial transmission in intensive care units (ICUs). Methods: A before and after (quasi-experimental) study was conducted in two ICUs at the Mahidol University Faculty of Medicine Ramathibodi Hospital with 3 months of observational period followed by 9 months of interventional period. All patients were screened for CRAB using both the culture and LAMP method from rectal swab and/or bronchial aspirates (intubated patients only) upon admission, weekly thereafter, and upon discharge. During the pre-intervention period, we performed contact precautions based on culture results. In contrast, during the intervention period, we initiated contact precautions within a few hours after sample collection on the basis of LAMP results. Results: A total of 1335 patients were admitted to the ICUs, of which 866 patients (pre-intervention period: 187; intervention period: 679) were eligible for this study. Incidence rate of CRAB infection decreased to 20.9 per 1000 patient-days in the intervention period from 35.2 in the pre-intervention period (P < 0.02). The calculated hazard ratio of CRAB transmission was 0.65 (95% confidence interval [CI], 0.44-0.97). Risk factors for CRAB acquisition included exposure to carbapenem (hazard ratio, 2.54 [95% CI: 1.61-5.57]). Conclusions: LAMP screening for CRAB upon ICU admission proved feasible for routine clinical practice. Rapid screening using LAMP followed by early intervention may reduce CRAB transmission rates in ICUs when compared to conventional intervention.

DOI： 10.1186/s13756-019-0564-9

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Antibiotic-associated adverse drug events at a Japanese academic hospital. Reviewed International journal

Ryohei Kokado, Hideharu Hagiya, Toshihiro Koyama, Eiko Matsui, Hideo Okuno, Daiichi Morii, Shigeto Hamaguchi, Hisao Yoshida, Yoshihiro Miwa, Kazunori Tomono

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   25 ( 5 )   392 - 395   2019.5

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INTRODUCTION: To promote antimicrobial stewardship activity, an understanding of the incidence of antibiotic-associated adverse drug events (ADEs) is essential. In this study, we aimed to describe the occurrence of antibiotic-associated ADEs at our hospital. METHODS: We retrospectively searched the ADE registration system in Osaka University Hospital between 2010 and 2017. Registrations of ADEs were dependent on the patients' drug history and clinical course after hospitalization. We classified the data according to types of ADEs (gastrointestinal, hepatobiliary, renal, cardiac, respiratory, hematologic, neurologic, dermatologic, and musculoskeletal) and antibiotic class. RESULTS: During the study period, we found 707 cases of antibiotic-associated ADEs, accounting for 22.3% of all the cases. Beta-lactam antibiotics constitute more than half of the cases (51.3%). The most common ADE was dermatologic abnormalities (53.4%), followed by liver dysfunction (9.7%) and gastrointestinal symptoms (8.9%). Among all antibiotics, oral third-generation cephalosporins were frequently reported as offending drugs (107 cases), accounting for 29.5% of beta-lactam ADEs and 46.3% of cephem ADEs. CONCLUSION: Antibiotic-associated ADEs covered approximately 20% of all the ADEs at our hospital. We believe that the data would be helpful in ensuring patient safety by promoting antimicrobial stewardship in hospitals.

DOI： 10.1016/j.jiac.2018.11.002.

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Association between rapid antigen detection tests and antibiotics for acute pharyngitis in Japan: A retrospective observational study. Reviewed International journal

Yusuke Teratani, Hideharu Hagiya, Toshihiro Koyama, Ayako Ohshima, Yoshito Zamami, Yasuhisa Tatebe, Ken Tasaka, Kazuaki Shinomiya, Yoshihisa Kitamura, Toshiaki Sendo, Shiro Hinotsu, Mitsunobu R Kano

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   25 ( 4 )   267 - 272   2019.4

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The application and clinical impact of rapid antigen detection test (RADT) in the treatment of acute pharyngitis is unknown in Japan. We aimed to examine the proportions of RADT usage to identify Group A β-hemolytic Streptococcus (GAS) in outpatients with acute pharyngitis and evaluate the association between RADT and antibiotic treatment. We analyzed health insurance claims data from 2013 to 2015. Logistic regression models were used to analyze associated factors with RADT, overall antibiotic prescription, or penicillin use. We analyzed 1.27 million outpatient visits with acute pharyngitis, in which antibiotics were prescribed in 59.3% of visits. Of the total visits, 5.6% of patients received RADT, and 10.8% of the antibiotics were penicillin. Penicillin selection rates were higher in cases with RADT (25.4%) than those without RADT (9.7%). Compared to large-scale facilities, antibiotic prescription rates were higher in physicians' offices. For factor analysis, age (3-15 years), diagnosis code (streptococcal pharyngitis), size of the medical facility (large-scale hospitals), and physician's specialty (pediatrics) were associated with RADT use. Penicillin selection rate increased with RADT implementation (25.4% vs. 9.7%: adjusted odds ratio 1.55; 95% CI, 1.50-1.60). At 63% of the facilities, the RADT implementation rate was <5% of acute pharyngitis visits prescribed antibiotics. In conclusion, the proportion of RADT usage for outpatients with acute pharyngitis was low in Japan. With appropriate indication and evaluation, we expect that more utilization of RADT can help promote antimicrobial stewardship for outpatients with acute pharyngitis by prompting penicillin therapy. Further investigation with detailed clinical data are warranted.

DOI： 10.1016/j.jiac.2018.12.005

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Repeated Left Upper Abdominal Pain. Reviewed

Kazuhiro Hongyo, Futoshi Nakagami, Hideharu Hagiya, Hiromi Rakugi

Internal medicine (Tokyo, Japan)   58 ( 6 )   893 - 893   2019.3

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DOI： 10.2169/internalmedicine.1900-18

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Fastidious spiral bacilli causing backbone infections after gastroenteritis. International journal

Koichiro Lee, Hideharu Hagiya, Misaki Kageyama, Futoshi Nakagami

BMJ case reports   12 ( 3 )   2019.3

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DOI： 10.1136/bcr-2018-228290

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Spreading Patterns of NDM-Producing Enterobacteriaceae in Clinical and Environmental Settings in Yangon, Myanmar. Reviewed International journal

Yo Sugawara, Yukihiro Akeda, Hideharu Hagiya, Noriko Sakamoto, Dan Takeuchi, Rathina Kumar Shanmugakani, Daisuke Motooka, Isao Nishi, Khwar Nyo Zin, Mya Mya Aye, Thuzar Myint, Kazunori Tomono, Shigeyuki Hamada

Antimicrobial agents and chemotherapy   63 ( 3 )   2019.3

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The spread of carbapenemase-producing Enterobacteriaceae (CPE), contributing to widespread carbapenem resistance, has become a global concern. However, the specific dissemination patterns of carbapenemase genes have not been intensively investigated in developing countries, including Myanmar, where NDM-type carbapenemases are spreading in clinical settings. In the present study, we phenotypically and genetically characterized 91 CPE isolates obtained from clinical (n = 77) and environmental (n = 14) samples in Yangon, Myanmar. We determined the dissemination of plasmids harboring genes encoding NDM-1 and its variants using whole-genome sequencing and plasmid analysis. IncFII plasmids harboring bla NDM-5 and IncX3 plasmids harboring bla NDM-4 or bla NDM-7 were the most prevalent plasmid types identified among the isolates. The IncFII plasmids were predominantly carried by clinical isolates of Escherichia coli, and their clonal expansion was observed within the same ward of a hospital. In contrast, the IncX3 plasmids were found in phylogenetically divergent isolates from clinical and environmental samples classified into nine species, suggesting widespread dissemination of plasmids via horizontal transfer. Half of the environmental isolates were found to possess IncX3 plasmids, and this type of plasmid was confirmed to transfer more effectively to recipient organisms at a relatively low temperature (25°C) compared to the IncFII plasmid. Moreover, various other plasmid types were identified harboring bla NDM-1, including IncFIB, IncFII, IncL/M, and IncA/C2, among clinical isolates of Klebsiella pneumoniae or Enterobacter cloacae complex. Overall, our results highlight three distinct patterns of the dissemination of bla NDM-harboring plasmids among CPE isolates in Myanmar, contributing to a better understanding of their molecular epidemiology and dissemination in a setting of endemicity.

DOI： 10.1128/AAC.01924-18

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Mycobacterium avium complex infection mimicking lung cancer. International journal

Hideharu Hagiya

BMJ case reports   12 ( 2 )   2019.2

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DOI： 10.1136/bcr-2018-228847

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PCR-Dipstick-Oriented Surveillance and Characterization of mcr-1- and Carbapenemase-Carrying Enterobacteriaceae in a Thai Hospital. Reviewed International journal

Rathina Kumar Shanmugakani, Yukihiro Akeda, Yo Sugawara, Warawut Laolerd, Narong Chaihongsa, Suntariya Sirichot, Norihisa Yamamoto, Hideharu Hagiya, Daiichi Morii, Yoshihiro Fujiya, Isao Nishi, Hisao Yoshida, Dan Takeuchi, Noriko Sakamoto, Kumthorn Malathum, Pitak Santanirand, Kazunori Tomono, Shigeyuki Hamada

Frontiers in microbiology   10   149 - 149   2019.2

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Colistin is used as an alternative therapeutic for carbapenemase-producing Enterobacteriaceae (CPE) infections which are spreading at a very high rate due to the transfer of carbapenemase genes through mobile genetic elements. Due to the emergence of mcr-1, the plasmid-mediated colistin resistance gene, mcr-1-positive Enterobacteriaceae (MCRPEn) pose a high risk for the transfer of mcr-1-carrying plasmid to CPE, leading to a situation with no treatment alternatives for infections caused by Enterobacteriaceae possessing both mcr-1 and carbapenemase genes. Here, we report the application of PCR-dipstick-oriented surveillance strategy to control MCRPEn and CPE by conducting the PCR-dipstick technique for the detection of MCRPEn and CPE in a tertiary care hospital in Thailand and comparing its efficacy with conventional surveillance method. Our surveillance results showed a high MCRPEn (5.9%) and CPE (8.7%) carriage rate among the 219 rectal swab specimens examined. Three different CPE clones were determined by pulsed-field gel electrophoresis (PFGE) whereas only two MCRPEn isolates were found to be closely related as shown by single nucleotide polymorphism-based phylogenetic analysis. Whole genome sequencing (WGS) and plasmid analysis showed that MCRPEn carried mcr-1 in two plasmids types-IncX4 and IncI2 with ~99% identity to the previously reported mcr-1-carrying plasmids. The identification of both MCRPEn and CPE in the same specimen indicates the plausibility of plasmid-mediated transfer of mcr-1 genes leading to the emergence of colistin- and carbapenem-resistant Enterobacteriaceae. The rapidity (<2 h) and robust sensitivity (100%)/specificity (~99%) of PCR-dipstick show that this specimen-direct screening method could aid in implementing infection control measures at the earliest to control the dissemination of MCRPEn and CPE.

DOI： 10.3389/fmicb.2019.00149

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An uncommon cause of leg oedema. Reviewed International journal

Naito T, Hagiya H, Nakagami F, Yamamoto K

BMJ case reports   12 ( 1 )   2019.1

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DOI： 10.1136/bcr-2018-228888

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Acute Non-calcific Retropharyngeal Tendinitis. Reviewed

Futoshi Nakagami, Hideharu Hagiya, Hiromi Rakugi

Internal medicine (Tokyo, Japan)   57 ( 23 )   3499 - 3500   2018.12

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DOI： 10.2169/internalmedicine.1127-18

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Persistent methicillin-resistant Staphylococcus aureus bacteremia owing to placental abscess. Reviewed International journal

Naomi Maeda, Hideharu Hagiya, Tsuyoshi Takiuchi, Shinsuke Kusakabe, Tetsuo Maeda, Keigo Kimura, Sayuri Iwai, Keisuke Kawasaki, Yumiko Hori, Eiichi Morii, Yuzuru Kanakura, Tadashi Kimura, Kazunori Tomono

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   24 ( 12 )   975 - 979   2018.12

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Staphylococcus aureus as a pathogen in human gestational membranes, a rather rare phenomenon, has recently been the focus of several researches. S. aureus forms biofilms on these membranes and potentially causes chorioamnionitis in pregnant women. We report a case of persistent methicillin-resistant S. aureus (MRSA) bacteremia owing to placental infection, causing chorioamnionitis and preterm birth. A 29-year-old Japanese woman at the 27th gestational week was diagnosed with acute promyelocytic leukemia and underwent all-trans retinoic acid therapy. Soon after hospitalization, the patient presented with persistent MRSA bacteremia of unknown origin. Despite various antimicrobial therapies, she experienced 12 MRSA bacteremia episodes over 6 weeks. However, after child birth, MRSA bacteremia disappeared without any complications. A pathologic examination of her placenta revealed placenta abscess, resulting in a diagnosis of MRSA-associated chorioamnionitis. Molecular analysis proved that a single MRSA strain (SCCmec Type IVa), which tested negative for Panton-Valentine leukocidin and toxic shock syndrome toxin-1, caused the obstinate infection. We should be aware that persistent MRSA bacteremia in pregnant women can originate from placental abscess.

DOI： 10.1016/j.jiac.2018.05.001

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Swollen Extraocular Muscle and Tingling Extremities. Reviewed International journal

Futoshi Nakagami, Hideharu Hagiya, Akane Oyama, Kazuhiro Hongyo, Motonori Nagasawa, Hiromi Rakugi

The American journal of medicine   131 ( 12 )   e492-e493   2018.12

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DOI： 10.1016/j.amjmed.2018.08.007

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Trends in Polypharmacy in Japan: A Nationwide Retrospective Study. Reviewed International journal

Hiroshi Onoue, Toshihiro Koyama, Yoshito Zamami, Hideharu Hagiya, Yasuhisa Tatebe, Naoko Mikami, Kazuaki Shinomiya, Yoshihisa Kitamura, Shiro Hinotsu, Toshiaki Sendo, Yasuyoshi Ouchi, Mitsunobu R Kano

Journal of the American Geriatrics Society   66 ( 12 )   2267 - 2273   2018.12

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OBJECTIVES: To describe and examine trends in polypharmacy according to age in Japan from 2010 to 2016. DESIGN: Retrospective observational study. SETTING: Outpatient settings. PARTICIPANTS: Japanese individuals aged 20 and older. MEASUREMENTS: We analyzed pharmacy claims data that the Japanese Ministry of Health, Labor, and Welfare provided in the Survey of Medical Care Activities in Public Health Insurance from 2010 to 2016. The use of 5 or more oral prescription medications per month was defined as polypharmacy and of 10 or more as excessive polypharmacy. Regression analysis was used to estimate trends in polypharmacy with annual percentage changes. Using number of medications (polypharmacy vs excessive polypharmacy), trends in polypharmacy and crude and age-adjusted rates of polypharmacy per 1,000 persons were calculated according to year and age group (20-34, 35-49, 50-64, 65-79, ≥ 80). RESULTS: We analyzed 240 million pharmacy claims data. The age-adjusted monthly prevalence rate of polypharmacy increased from 85.2 to 93.8 per 1,000 persons per month and of excessive polypharmacy from 13.6 to 14.0 per 1,000 persons per month from 2010 to 2016 in the entire study population. The highest rate of polypharmacy (per 1,000 persons) was observed in 2016 in those aged 80 and older (326.8), followed by those aged 65 to 79 (167.3). The polypharmacy rate increased by 6.3% (95% confidence interval (CI)=4.0-8.7) per year from 2010 to 2012, then decreased by 0.7% (95% CI=-1.3-0.0) per year from 2012 to 2016. The rate of excessive polypharmacy increased by 4.5% (95% CI=1.1-8.0) per year from 2010 to 2013 and then decreased by 3.7% (95% CI=-6.7 to -0.6) per year from 2013 to 2016. CONCLUSION: The overall trend of polypharmacy in Japan increased during the study period, although the increase ceased in 2013 and then declined from 2013 to 2016. Policy changes in Japan might be responsible for some of the changes. J Am Geriatr Soc 66:2267-2273, 2018.

DOI： 10.1111/jgs.15569

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Oral shingles. Reviewed International journal

Hagiya H, Nakagami F, Isomura E

BMJ case reports   11 ( 1 )   2018.12

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DOI： 10.1136/bcr-2018-228383

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Emergence of daptomycin non-susceptible coagulase-negative Staphylococci in patients with cardiovascular device infections: Two cases report investigated by whole genome analysis. Reviewed International journal

Hagiya H, Sugawara Y, Kimura K, Hamaguchi S, Nishi I, Hayashi M, Akeda Y, Tomono K

Medicine   97 ( 49 )   e13487   2018.12

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RATIONALE: Daptomycin (DAP) is a key drug for treating severe Staphylococcus infections. The emergence of DAP non-susceptible Staphylococcus aureus has been widely recognized in clinical situations, although the clinical status of DAP non-susceptible coagulase-negative Staphylococcus (CoNS) infections is unclear. We encountered 2 cases of cardiovascular device infections that were associated with DAP non-susceptible CoNS. PATIENT CONCERNS: The first case involved a 60-year-old woman with a pump pocket infection in a left ventricular assist device. DAP non-susceptible Staphylococcus capitis subsp. ureolyticus was isolated from a blood culture after treatment using vancomycin (10 days) and DAP (6 days). The second case involved a 71-year-old man with an aortic graft infection. DAP non-susceptible S capitis subsp. ureolyticus was detected in pus after treatment using vancomycin (2 weeks) and DAP (1 week) without complete removal and debridement. DIAGNOSIS: Cardiovascular device infections caused by DAP non-susceptible CoNS. INTERVENTIONS AND OUTCOMES: Whole genome sequencing of these strains revealed multiple mutations in genes that are related to DAP-non-susceptibility in S aureus, which created amino acid substitutions in mprF, dltAB, dltD, rpoC, yycG, cls2, pgsA, and vraSR. To the very best of our knowledge, the substitution patterns were not identical to those previously reported in DAP non-susceptibile S aureus. LESSONS: Clinicians should be cautious regarding the emergence of DAP non-susceptible CoNS, especially in cases with implanted prosthetic devices, inadequate debridement, and prior usage of vancomycin and DAP. Further studies are needed to understand the relevance of these genetic changes and DAP-non-susceptibility in CoNS strains.

DOI： 10.1097/MD.0000000000013487

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Daptomycin-associated myopathy induced by concomitant administration of mirabegron. Reviewed International journal

Hagiya H, Kokado R, Okuno H, Tomono K

Infection   47 ( 2 )   331 - 332   2018.11

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DOI： 10.1007/s15010-018-1252-z

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Trends in incidence and mortality of tuberculosis in Japan: a population-based study, 1997-2016. Reviewed International journal

Hagiya H, Koyama T, Zamami Y, Minato Y, Tatebe Y, Mikami N, Teratani Y, Ohshima A, Shinomiya K, Kitamura Y, Sendo T, Hinotsu S, Tomono K, Kano MR

Epidemiology and Infection   147   1 - 10   2018.11

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Japan is still a medium-burden tuberculosis (TB) country. We aimed to examine trends in newly notified active TB incidence and TB-related mortality in the last two decades in Japan. This is a population-based study using Japanese Vital Statistics and Japan Tuberculosis Surveillance from 1997 to 2016. We determined active TB incidence and mortality rates (per 100 000 population) by sex, age and disease categories. Joinpoint regression was applied to calculate the annual percentage change (APC) in age-adjusted mortality rates and to identify the years showing significant trend changes. Crude and age-adjusted incidence rates reduced from 33.9 to 13.9 and 37.3 to 11.3 per 100 000 population, respectively. Also, crude and age-adjusted mortality rates reduced from 2.2 to 1.5 and 2.8 to 1.0 per 100 000 population, respectively. Average APC in the incidence and mortality rates showed significant decline both in men (-6.2% and -5.4%, respectively) and women (-5.7% and -4.6%, respectively). Age-specific analysis demonstrated decreases in incidence and mortality rates for every age category, except for the incidence trend in the younger population. Although trends in active TB incidence and mortality rates in Japan have favourably decreased, the rate of decline is far from achieving TB elimination by 2035.

DOI： 10.1017/S095026881800290X

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Broad-spectrum antibiotic prescriptions are unevenly discontinued throughout the week. Reviewed International journal

Kokado R, Hagiya H, Morii D, Okuno H, Yamamoto N, Hamaguchi S, Yoshida H, Miwa Y, Tomono K

The Journal of hospital infection   101 ( 4 )   471 - 474   2018.11

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In order to investigate prescribing patterns of in-hospital broad-spectrum antibiotics (antimeticillin-resistant Staphylococcus aureus drugs, carbapenems and piperacillin/tazobactam), data on the distribution of antibiotic initiation and discontinuation throughout the week were analysed at Osaka University Hospital, Japan. No significant differences in the number of initiations were found between weekdays. However, broad-spectrum antibiotics were disproportionately discontinued on Tuesdays or on the second day after a holiday. This study suggests that broad-spectrum antibiotics tend to be continued over weekends or holidays and discontinued thereafter; this is likely to be due to behavioural factors beyond medical indications, and needs to be addressed in future antimicrobial stewardship initiatives.

DOI： 10.1016/j.jhin.2018.11.004

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Roseomonas mucosa bacteremia in a neutropenic child: A case report and literature review. International journal

Keigo Kimura, Hideharu Hagiya, Isao Nishi, Hisao Yoshida, Kazunori Tomono

IDCases   14   e00469   2018.11

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Roseomonas species is rarely found to be pathogenic to humans and there are few clinical cases that have been described in the literature. We report a case of Roseomonas mucosa bacteremia that involved a 9-year-old Japanese boy who was in a condition of febrile neutropenia caused by chemotherapy for cerebellar medulloblastoma. Conventional phenotyping failed to identify the organism; however, genetic analysis using 16S rDNA sequencing confirmed the pathogen to be R. mucosa. The patient recovered following treatment by meropenem without any complications. A literature review of pediatric cases of Roseomonas bacteremia identified 12 other documented cases, and these revealed that a common clinical situation for the infection is an immunocompromised state with malignancy and/or an indwelling intravenous catheter. Because of the low number of cases, the overall picture of Roseomonas bacteremia in children remains to be elucidated; however, the prognosis of the infection appears to be satisfactory.

DOI： 10.1016/j.idcr.2018.e00469.

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Neurosyphilis concurrently involving eye and ear. Reviewed International journal

Futoshi Nakagami, Hideharu Hagiya, Kazuichi Maruyama, Yuri Onishi

BMJ case reports   2018   2018.10

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DOI： 10.1136/bcr-2018-227185

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Reduced Seroprevalence of Hepatitis A Virus Among Japanese Healthcare Workers as a Risk Factor for Occupational Infection. Reviewed International journal

Yoshioka N, Deguchi M, Hagiya H, Kagita M, Tomono K

Clinical laboratory   64 ( 10 )   1791 - 1793   2018.10

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BACKGROUND: With the improvement in sanitation and hygiene, the incidence of hepatitis A virus (HAV) infection has declined, and its seroprevalence among Japanese people has been reduced. Universal HAV vaccination is yet to be implemented in Japan, and the healthcare workers (HCWs) are at higher risks of acquiring this infection. We herein report the seroepidemiology of HAV infection among HCWs at Osaka University Hospital. METHODS: Between September and October 2017, we collected serum samples submitted to our laboratory for HCWs health examination and tested for the anti-HAV antibody. RESULTS: Overall HAV seropositivity rate was 5.1% (22/436 samples). The seroprevalence was higher among those in the twenties (6.0%) and thirties (8.0%), compared to older age groups. CONCLUSIONS: In this age of internationalization, the decreasing immunity for HAV places HCWs at risk of developing the disease. As a preventive measure against occupational infection, HAV vaccination may be needed for Japanese HCWs.

DOI： 10.7754/Clin.Lab.2018.180518

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Trends in Polypharmacy in Japan: A Nationwide Retrospective Study. Reviewed

Onoue H, Koyama T, Zamami Y, Hagiya H, Tatebe Y, Mikami N, Shinomiya K, Kitamura Y, Hinotsu S, Sendo T, Ouchi Y, Kano MR

Journal of the American Geriatrics Society   2018.10

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Pasteurella multocida multiple intrapelvic abscesses in a young woman with uterine cervical cancer. Reviewed International journal

Kimura K, Hagiya H, Yamamoto N, Yoshida H, Akeda Y, Nishi I, Tomono K

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   25 ( 3 )   197 - 199   2018.9

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Pasteurella multocida, a zoonotic pathogen in humans, is known to be associated with skin and soft tissue infections following animal bites, but rarely causes visceral infections. We report a case of P. multocida-associated multiple intrapelvic abscesses in a young woman with uterine cervical cancer. A 29-year-old unmarried woman was referred to us because of prolonged high fever accompanying abdominal pain with muscular guarding. She had a domestic cat but denied of any bites or scratches before that. Computed tomography demonstrated ascites and multiple abscesses around her uterus. Her condition did not improve with an initial treatment with flomoxef, clindamycin, and azithromycin. Further, we performed percutaneous pus drainage and switched the antimicrobial therapy to a combination of piperacillin/tazobactam and minocycline for 10 days. Although P. multocida was isolated from vaginal culture, no organisms were isolated from the pus culture. However, further investigation with specimen-direct 16S rDNA analysis diagnosed P. multocida as possibly a single pathogen responsible for the intrapelvic infection. After taking oral levofloxacin for two weeks, no recurrence was reported. Although P. multocida is known as an animal-related pathogen, it can transmit to humans without apparent bites or scratches. The present case illustrates that P. multocida can cause intrapelvic abscess as a result of ascending genital infection.

DOI： 10.1016/j.jiac.2018.07.019

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Genomic reorganization by IS26 in a blaNDM-5-bearing FII plasmid of Klebsiella pneumoniae isolated from a patient in Japan. Reviewed International journal

Takeuchi D, Akeda Y, Yoshida H, Hagiya H, Yamamoto N, Nishi I, Yoshioka N, Sugawara Y, Sakamoto N, Shanmugakani RK, Deguchi M, Tomono K, Hamada S

Journal of medical microbiology   67 ( 9 )   1221 - 1224   2018.9

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An NDM-5-producing Klebsiella pneumoniae ST147 strain was isolated from a Japanese patient who had not travelled abroad in at least 5 years. Whole-genome sequencing revealed a genomic rearrangement in an FII plasmid harbouring bla due to the replicative transposition of IS26. A hypothetical structure was proposed for its ancestral plasmid, and comparative genomic analysis of the plasmid suggested the dissemination of structurally similar plasmids harbouring bla in Asian and Middle Eastern countries. NDM-5 NDM-5

DOI： 10.1099/jmm.0.000817

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Genomic reorganization by IS26 in a blaNDM-5-bearing FII plasmid of Klebsiella pneumoniae isolated from a patient in Japan Reviewed

akeuchi D, Akeda Y, Yoshida H, Hagiya H, Yamamoto N, Nishi I, Yoshioka N, Sugawara Y, Sakamoto N, Shanmugakani RK, Deguchi M, Tomono K, Hamada S

J Med Microbio   67 ( 9 )   1221 - 1224   2018.8

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DOI： 10.1099/jmm.0.000817.

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Liver abscess caused by Gram-negative spiral bacilli. Reviewed International journal

Hagiya H, Kimura K, Nishi I, Tomono K

JMM case reports   5 ( 7 )   e005155   2018.7

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DOI： 10.1099/jmmcr.0.005155

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Vaccination strategy for epidemic viral diseases in healthcare workers: Cut-off for optimal immunization. Reviewed International journal

Yoshioka N, Deguchi M, Hagiya H, Kagita M, Tsukamoto H, Takao M, Tomono K

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   25 ( 1 )   78 - 81   2018.7

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Healthcare workers (HCWs) are at an increased risk of being exposed to epidemic viral diseases (EVDs), such as measles, rubella, mumps, and varicella-zoster. Currently, in case of the absence of written records on previous immunizations, the Japanese Society for Infection Prevention and Control guidelines require HCWs to have antibody titers higher than laboratory thresholds, possibly leading to over-immunization. We report our vaccination strategy and the consequent incidences of EVDs at the Osaka University Hospital between 2000 and 2016. In 2001, we initiated an annual serology check of antibody titers against EVDs and immunization for newly employed HCWs. As an additional vaccination program, all HCWs with low antibody titers were vaccinated in 2005 and 2010. Antibody titers were determined by an enzyme immunoassay (EIA), with a positive range of >2.0 cut-off index. After implementing the vaccination strategy to keep the laboratory threshold, there were only sporadic cases of EVDs among HCWs. More than 99% of individuals who had positive titers in 2005 remained the positive antibody titers in 2010, indicating that a minimum interval of 5 years is enough to measure immunity. Unprotected workers can, even silently, transmit the contagious viruses to patients and coworkers, possibly resulting in a nosocomial outbreak. However, over-vaccination may yield adverse effects and financial burdens. Our observational data indicate that the laboratory cut-off index of >2.0 by EIA may provide a sufficient herd immunity to prevent EVDs among HCWs.

DOI： 10.1016/j.jiac.2018.07.008

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Spread of blaNDM-carrying plasmids among clinical and wastewater isolates of Enterobacteriaceae in Myanmar

Sugawara Y, Akeda Y, Sakamoto N, Takeuchi D, Yamamoto N, Hagiya H, Tomono K, Hamada S

2018.6

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Persistent methicillin-resistant Staphylococcus aureus bacteremia owing to placental abscess. Reviewed

Maeda N, Hagiya H, Takiuchi T, Kusakabe S, Maeda T, Kimura K, Iwai S, Kawasaki K, Hori Y, Morii E, Kanakura Y, Kimura T, Tomono K

J Infect Chemother   18   30125 - 30129   2018.5

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Helicobacter cinaedi-associated Carotid Arteritis. Reviewed

Shinichiro Nakao, Hideharu Hagiya, Keigo Kimura, Tomomi Mitsui, Akane Oyama, Kazuhiro Hongyo, Yusuke Takahashi, Futoshi Nakagami, Kazunori Tomono, Hiromi Rakugi

Acta medica Okayama   72 ( 2 )   189 - 192   2018.4

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A 65-year-old Japanese man with bilateral carotid atherosclerosis presented with right neck pain and fever. Contrast-enhanced computed tomography suggested carotid arteritis, and carotid ultrasonography showed an unstable plaque. The patient developed a cerebral embolism, causing a transient ischemic attack. Helicobacter cinaedi was detected in blood culture, and H. cinaedi-associated carotid arteritis was diagnosed. Empirical antibiotic therapy was administered for 6 weeks. After readmission for recurrent fever, he was treated another 8 weeks. Although the relationship between H. cinaedi infection and atherosclerosis development remains unclear, the atherosclerotic changes in our patient's carotid artery might have been attributable to H. cinaedi infection.

DOI： 10.18926/AMO/55861

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Silent Native-valve Endocarditis Caused by Propionibacterium acnes. Reviewed

Yamamoto R, Miyagawa S, Hagiya H, Kimura K, Nishi I, Yamamoto N, Yoshida H, Akeda Y, Tomono K, Toda K, Sawa Y

Internal medicine (Tokyo, Japan)   57 ( 16 )   2417 - 2420   2018.3

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We describe a rare case of Propionibacterium acnes native-valve endocarditis that silently progressed in a 67-year-old man with hybrid dialysis. The patient was scheduled for kidney transplantation, and pre-operative investigation incidentally detected a vegetative structure at his native mitral valve that had increased in size. He underwent cardiac surgery and P. acnes was detected in cultures of a resected cardiac valve specimen and blood. This case highlights that P. acnes can silently cause infective endocarditis in a native-valve, and that physicians should consider the possibility of infection when P. acnes is isolated in blood cultures.

DOI： 10.2169/internalmedicine.9833-17

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ミャンマー連邦共和国の臨床及び環境由来町内細菌科細菌におけるNDM搭載プラスミドの伝播

菅原 庸, 明田 幸宏, 萩谷 英大, 坂本 典子, 竹内 壇, 山本 倫久, 岡田 和久, 朝野 和典, 浜田 茂幸

2018.3

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Desulfovibrio desulfuricans bacteremia: A case report and literature review Reviewed International journal

Hideharu Hagiya, Keigo Kimura, Isao Nishi, Norihisa Yamamoto, Hisao Yoshida, Yukihiro Akeda, Kazunori Tomono

Anaerobe   49   112 - 115   2018.2

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Desulfovibrio spp. are sulfate-reducing, anaerobic bacteria that are ubiquitously found in the environment. These organisms infrequently cause human infections, and the clinical characteristics of infection with Desulfovibrio spp. remain unclear. Here, we describe a case of Desulfovibrio desulfuricans bacteremia in an 88-year-old Japanese man with a past medical history of thoracic endovascular aortic repair (TEVAR). His chief complaint was hemoptysis for 2 weeks. A chest contrast-enhanced computed tomography demonstrated an enlarged thoracic aortic aneurysm surrounded by a ring-enhanced lesion, recognized as mediastinal abscess. Gram-negative spiral bacilli were detected in anaerobic blood culture. These bacteria could not be identified using conventional methods, but by analyzing a full base sequence of 16S rDNA, they were identified as D. desulfuricans subsp. desulfuricans. The patient underwent an emergent re-TEVAR, and the infection subsided after being treated with tazobactam/piperacillin and clindamycin, followed by metronidazole. A literature review of previous cases of D. desulfuricans bacteremia suggested that the pathogen was derived from bacterial translocation from the intestine in most cases. Desulfovibrio infection is presumably underestimated due to its infrequency, indolent growth, and difficulty in identification. Desulfovibrio spp. should be suspected when spiral rods are observed in anaerobic culture, and molecular analysis is required for accurate species-level differentiation of the pathogens. To better understand the pathogenicity of these fastidious organisms, further cases based on the exact bacterial identification should be investigated.

DOI： 10.1016/j.anaerobe.2017.12.013

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Emergence of Carbapenem Non-susceptible Campylobacter coli after Long-term Treatment against Recurrent Bacteremia in a Patient with X-linked Agammaglobulinemia. Reviewed

Hagiya H, Kimura K, Nishi I, Yoshida H, Yamamoto N, Akeda Y, Tomono K

Internal medicine (Tokyo, Japan)   57 ( 14 )   2077 - 2080   2018.2

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We herein report a case of recurrent Campylobacter coli bacteremia in a 37-year-old Japanese man with X-linked agammaglobulinemia (XLA). The patient experienced seven episodes of C. coli bacteremia over one year, with an erythematous rash intermittently emerged on the lower limbs. Although hospitalization for intravenous treatment was repeatedly recommended, he obstinately declined it. Following long-term oral antibiotic treatment with tebipenem and faropenem for the persistent infection, C. coli showed elevated minimum inhibitory concentrations to meropenem, a key drug for severe campylobacteriosis. Physicians should note that the overuse of antibiotics can lead to the emergence of carbapenem-non-susceptible Campylobacter strains.

DOI： 10.2169/internalmedicine.0312-17

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Emergence of Carbapenem Non-susceptible Campylobacter coli after Long-term Treatment against Recurrent Bacteremia in a Patient with X-linked Agammaglobulinemia. Reviewed

Hagiya H, Kimura K, Nishi I, Yoshida H, Yamamoto N, Akeda Y, Tomono K

Internal Medicine   2018.2

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DOI： 10.2169/internalmedicine.0312-17

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Available, Bed-sided, Comprehensive (ABC) score to a diagnosis of Methicillin-resistant Staphylococcus aureus infection: A derivation and validation study Reviewed International journal

Nori Yoshioka, Matsuo Deguchi, Hideharu Hagiya, Hisao Yoshida, Norihisa Yamamoto, Shoji Hashimoto, Yukihiro Akeda, Kazunori Tomono

BMC Infectious Diseases   18 ( 1 )   19 - 19   2018.1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

Background: Methicillin-resistant Staphylococcus aureus (MRSA) infections continue to be a leading problem in health care facilities worldwide. Methods: This single-center retrospective cohort study consisted of a derivation phase and a validation phase. The derivation phase included all patients admitted to Osaka University Hospital between May 2010 and April 2011. We proposed a provisional available, bed-sided, comprehensive (ABC) score, and evaluated its accuracy using the clinical diagnosis as a reference. We subsequently revised ABC scores based on k coefficient scores of each variable this revision was validated by applying it to another patient population. Results: A total of 172 patients and 154 cases were enrolled in the derivation and validation studies, respectively. The revised ABC score consisted of four simple variables: type of clinical specimen (1 to 3 points), Gram-staining result (1 point), presence of local inflammation (2 points), and a systemic inflammatory response (2 points). A revised score of ≥5 points was sensitive (93.8%) and specific (90.6%), and the area under the receiver-operating curve was 0.969 (95% CI
0.957-1). Conclusions: We developed a simple and comprehensive scoring system for diagnosis of nosocomial MRSA infections
this system is applicable in a wide variety of situations.

File： 研究業績書　萩谷 (20180413).docx

DOI： 10.1186/s12879-017-2919-2

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Available, Bed-sided, Comprehensive (ABC) score to a diagnosis of Methicillin-resistant Staphylococcus aureus infection: A derivation and validation study Reviewed

Nori Yoshioka, Matsuo Deguchi, Hideharu Hagiya, Hisao Yoshida, Norihisa Yamamoto, Shoji Hashimoto, Yukihiro Akeda, Kazunori Tomono

BMC Infectious Diseases   18 ( 1 )   19   2018.1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

Background: Methicillin-resistant Staphylococcus aureus (MRSA) infections continue to be a leading problem in health care facilities worldwide. Methods: This single-center retrospective cohort study consisted of a derivation phase and a validation phase. The derivation phase included all patients admitted to Osaka University Hospital between May 2010 and April 2011. We proposed a provisional available, bed-sided, comprehensive (ABC) score, and evaluated its accuracy using the clinical diagnosis as a reference. We subsequently revised ABC scores based on k coefficient scores of each variable this revision was validated by applying it to another patient population. Results: A total of 172 patients and 154 cases were enrolled in the derivation and validation studies, respectively. The revised ABC score consisted of four simple variables: type of clinical specimen (1 to 3 points), Gram-staining result (1 point), presence of local inflammation (2 points), and a systemic inflammatory response (2 points). A revised score of ≥5 points was sensitive (93.8%) and specific (90.6%), and the area under the receiver-operating curve was 0.969 (95% CI
0.957-1). Conclusions: We developed a simple and comprehensive scoring system for diagnosis of nosocomial MRSA infections
this system is applicable in a wide variety of situations.

DOI： 10.1186/s12879-017-2919-2

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Clinical characteristics and outcome of critically ill patients with bacteremia caused by extended-spectrum β-lactamase-producing and non-producing Escherichia coli Reviewed International journal

Yuto Haruki, Hideharu Hagiya, Mai Haruki, Tetsuhiro Sugiyama

Journal of Infection and Chemotherapy   24 ( 11 )   944 - 947   2018

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Elsevier B.V.  

The number of patients infected with extended-spectrum beta-lactamase (ESBL)-producing organisms has increased dramatically worldwide, and high mortality rates are seen in severely ill patients. This study retrospectively compared the clinical characteristics and outcomes of critically ill patients in an intensive care unit (ICU) at the Tsuyama Chuo Hospital (Okayama, Japan) who were hospitalized for bacteremia caused by ESBL-producing Escherichia coli (ESBL-EC) or non-ESBL-producing E. coli (non-ESBL-EC) between January 2006 and December 2016 (11 years). We analyzed the patients' age, sex, underlying disease(s), sequential organ failure assessment scores, primary focus of bacteremia, empiric antibiotics, rate of appropriateness of empiric antibiotics, and treatment duration, with 28-day mortality being the primary outcome. The study included 24 patients with ESBL-EC bacteremia and 77 with non-ESBL-EC bacteremia. The rate of appropriate initial antibiotic treatment was significantly lower (54.2% vs. 96.1%, respectively
P &lt
0.01) and the mortality due to bacteremia significantly higher (37.5% vs. 15.6%, respectively
P = 0.04) in the ESBL-EC than in the non-ESBL-EC bacteremia group. A subgroup analysis focusing on patients who were administered appropriate empiric antibiotics showed that the 28-day mortality rate did not differ significantly between the two groups (P = 0.23). To our knowledge, this is the first study to compare the outcomes of patients with ESBL-EC and non-ESBL-EC bacteremia in a Japanese ICU setting. Initial empiric antibiotic therapy covering ESBL-producing pathogens should be considered for critically ill patients in the ICU.

DOI： 10.1016/j.jiac.2018.04.016

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Far east scarlet-like fever masquerading as adult-onset Kawasaki disease Reviewed

Kazuki Ocho, Masaya Iwamuro, Kou Hasegawa, Hideharu Hagiya, Kammei Rai, Tetsuya Yumoto, Fumio Otsuka

Internal Medicine   57 ( 3 )   437 - 440   2018

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A previously healthy 31-year-old man was referred to us with refractory septic shock accompanied by bilateral conjunctival congestion and erythema of his right lower limb. Nine days after admission, he had bilateral desquamation of the fingertips, and his presentation satisfied the criteria for Kawasaki disease. A serological examination was positive for Yersinia pseudotuberculosis, and he was diagnosed with Far East scarlet-like fever (FESLF). Interestingly, his 11-month-old baby boy had similar symptoms around the same time, indicating the intrafamilial transmission of the pathogen. We should consider FESLF when we encounter a familial occurrence of systemic manifestations of Kawasaki disease.

DOI： 10.2169/internalmedicine.9250-17

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Risk factors for fecal carriage of IMP-6-producing Enterobacteriaceae at a long-term care hospital in Japan: A follow-up report from the northern Osaka multicentre study group Reviewed International journal

Hideharu Hagiya, Norihisa Yamamoto, Ryuji Kawahara, Yukihiro Akeda, Rathina Kumar Shanmugakani, Akiko Ueda, Isao Nishi, Rumiko Asada, Hisao Yoshida, Kazunori Tomono

Journal of Infection and Chemotherapy   24 ( 9 )   769 - 772   2018

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The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) has been increasing at medical institutions in Japan without even noticing. Recently, we performed a point prevalence survey for CRE carriage at a medical facility in northern Osaka that demonstrated an unexpectedly high prevalence of blaIMP-6-positive CRE, particularly at long-term care hospitals (LTCH). To identify the risk factors for CRE carriage, we collected clinical data of patients at a representative LTCH. Of 140 patients who were included in this study, 27 (19.3%) were colonized with metallo-beta-lactamase (IMP-6) producers. Pulsed-field gel electrophoresis of the IMP-6 producing Enterobacteriaceae suggested a non-clonal transmission of Escherichia coli, while a clonal spread was shown for Klebsiella pneumoniae. Risk factors for CRE colonization were a longer stay at the hospital stay and a lower independence state, as measured by Norton scales. We propose that a paradigm shift in infection control, inciting a coordinated regional effort to involve LTCHs, should be discussed in the aging society of Japan.

DOI： 10.1016/j.jiac.2018.03.009

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Comparison of the temperature influence on the activity of currently available Procalcitonin reagents Reviewed International journal

Nori Yoshioka, Matsuo Deguchi, Hideharu Hagiya, Masanori Kagita, Satomi Yukawa, Yoh Hidaka, Kazunori Tomono

Clinical Laboratory   64 ( 1-2 )   201 - 204   2018

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Background: Procalcitonin (PCT) is a stable biomarker for bacterial infections
however, limited data is available on new trivalent reagents. We evaluated temperature influence on the activity of PCT reagents. Methods: Using both conventional and trivalent reagents, we measured PCT levels of 30 clinical samples, stored residuum at refrigerator (4°C) and room temperature (24°C), and reexamined it after 24 hours. We defined a reduction rate as a percentage of PCT level at 24 hours compared to that after defrost and evaluated a ratio of reduction rate in 4°C to that in 24°C. Results: The reduction rate at room temperature decreased significantly compared to that in the refrigerated condition for all the reagents examined (p &lt
0.001). In addition, the ratio of reduction rate between the conventional and trivalent reagents showed a significant difference (p &lt
0.001) Conclusions: The serum PCT levels significantly decrease at room temperature, particularly when using newer trivalent reagents.

DOI： 10.7754/Clin.Lab.2017.170510

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Panophthalmitis caused by Streptococcus dysgalactiae subsp. equisimilis: A case report and literature review Reviewed International journal

Hideharu Hagiya, Takuya Semba, Takeshi Morimoto, Norihisa Yamamoto, Hisao Yoshida, Kazunori Tomono

Journal of Infection and Chemotherapy   24 ( 11 )   936 - 940   2018

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Lancefield group G β-hemolytic Streptococcus dysgalactiae subspecies equisimilis (SDSE) has become a leading causative pathogen of invasive streptococcal infection. In this report, we describe a case of disseminated SDSE infection complicated by endogenous endophthalmitis, resulting in panophthalmitis and blindness. A 65-year-old man who underwent mitral valve replacement surgery two months previously was hospitalized due to high fever and right visual loss. A systemic investigation revealed endophthalmitis complicated by mediastinal abscess, prosthetic infective endocarditis, cerebral emboli and hemorrhage, and multiple arthritis. The patient underwent various surgeries, including vitrectomy, mediastinal lavage, mitral valve replacements, joint lavages, as well as an intensive antibiotic treatment. His general condition gradually improved, but the ocular infection developed to panophthalmitis, which ultimately required ophthalmectomy. A literature review regarding Group G-associated endogenous endophthalmitis suggested that the disease occurs in elderly people, is frequently complicated with endocarditis, and yields poor visual prognosis regardless of appropriate antibiotic treatment and surgical therapies. In this aging society, invasive infections with SDSE should be much more recognized among medical practitioners in order to improve patient prognosis.

DOI： 10.1016/j.jiac.2018.04.012

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Ceftriaxone-induced Neurotoxicity in a Patient after Pancreas-Kidney Transplantation. Reviewed

Hideharu Hagiya, Koji Miyawaki, Norihisa Yamamoto, Hisao Yoshida, Akihiro Kitagawa, Tadafumi Asaoka, Hidetoshi Eguchi, Yukihiro Akeda, Kazunori Tomono

Internal medicine (Tokyo, Japan)   56 ( 22 )   3103 - 3107   2017.11

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Ceftriaxone is a widely used third-generation cephalosporin showing advantageous pharmacokinetic properties and a broad antimicrobial spectrum. We herein report a case of ceftriaxone-induced neurotoxicity in a 56-year-old man on hemodialysis. Seven days after initiating high-dose ceftriaxone, the patient developed impaired consciousness along with facial myoclonus and sporadic phonation. The symptoms clearly disappeared shortly after withdrawal of the drug. Ceftriaxone is considered a safe antibiotic for patients with renal insufficiency, since it is excreted via both haptic and renal pathways. Physicians should note that antibiotic-associated encephalopathy may develop in patients administered ceftriaxone, especially in those complicated with renal dysfunction.

DOI： 10.2169/internalmedicine.8774-16

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Durability of immunity by hepatitis B vaccine in Japanese health care workers depends on primary response titers and durations Reviewed International journal

Nori Yoshioka, Matsuo Deguchi, Hideharu Hagiya, Masanori Kagita, Hiroko Tsukamoto, Miyuki Takao, Hisao Yoshida, Norihisa Yamamoto, Yukihiro Akeda, Yoshiko Nabetani, Ikuhiro Maeda, Yoh Hidaka, Kazunori Tomono

PLOS ONE   12 ( 11 )   e0187661   2017.11

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Background
Health care workers (HCWs) are frequently exposed to hepatitis B virus (HBV) infection. The efficacy and safety of immunization with the hepatitis B (HB) vaccine are well recognized, but the durability of immunity and need for booster doses in those with secondary vaccine response failure remains controversial.
Methods
This was a retrospective cohort study performed at Osaka University Hospital, Japan. We examined antibodies against HB surface antigen (anti-HBs) titers annually after immunization for previously non-immunized HCWs. Primary responders were categorized by their sero-positive durations as short responders (those whose anti-HBs titers declined to negative range within 3 years), and long responders (those who retained positive anti-HBs levels for 3 years and more). We re-immunized short responders with either single or 3-dose boosters, the long responders with a single booster when their titers dropped below protective levels, and examined their sero-protection rates over time thereafter.
Results
From 2001 to 2012, data of 264 HCWs with a median age of 25.3 were collected. The rate of anti-HBs positivity after primary vaccination were 93.0% after three doses (n = 229), 54.5% after two doses (n = 11), and 4.2% after a single dose (n = 24). Of 213 primary responders, the anti-HBs levels of 95 participants (44.6%) fell below the protective levels, including 46 short responders and 49 long responders. HCWs with higher initial anti-HBs titers after primary vaccination had significantly longer durations of sero-positivity. For short responders, 3-dose booster vaccination induced a longer duration of anti-HBs positivity compared to a single-dose booster, whereas for long responders, a single-dose booster alone could induce prolonged anti-HBs positivity.
Conclusion
Our preliminary data suggested that it may be useful to differentiate HB vaccine responders based on their primary response durations to maintain protective levels of anti-HBs efficiently. A randomized, prospective, large-scale study is warranted to support our findings.

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Prevalence of, and risk factors for, carriage of carbapenem-resistant Enterobacteriaceae among hospitalized patients in Japan Reviewed International journal

N. Yamamoto, R. Asada, R. Kawahara, H. Hagiya, Y. Akeda, R. K. Shanmugakani, H. Yoshida, S. Yukawa, K. Yamamoto, Y. Takayama, H. Ohnishi, T. Taniguchi, T. Matsuoka, K. Matsunami, I. Nishi, T. Kase, S. Hamada, K. Tomono

JOURNAL OF HOSPITAL INFECTION   97 ( 3 )   212 - 217   2017.11

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Background: The prevalence of carbapenem-resistant Enterobacteriaceae (CRE) has been reported to be lower in Japan than in many other countries. However, extensive surveillance for CRE carriage has not been performed in Japan.
Aim: To investigate the prevalence of CRE carriage in Japan among convalescent patients considered to be at high risk of being CRE carriers using an improved selective culture medium.
Methods: A cross-sectional survey was conducted in 22 acute care hospitals (ACHs) and 21 long-term care hospitals (LTCHs) in northern Osaka from December 2015 to January 2016. Patients who used incontinence aids, an enteral feeding tube or a urinary catheter were enrolled. Faecal specimens were examined using the newly developed M-ECC for imipenemase (IMP)-producing CRE, which is the most prevalent form of CRE in Japan. The positive isolates were analysed by polymerase chain reaction and sequencing. Risk factors associated with carriage were analysed by logistic regression.
Findings: Among 1507 patients, 184 (12.2%) carried CRE. The percentage of positive patients was significantly higher in LTCHs (14.9%) than in ACHs (3.6%) (P&lt;0.001). Risk factors for CRE carriage were longer hospital stay [odds ratio (OR) 2.59; 95% confidence interval (CI) 1.87-3.60], enteral feeding (OR 3.03, 95% CI 2.08-4.42) and antibiotic exposure (OR 2.00, 95% CI 1.40-2.87). Among the 233 CRE isolates identified, 223 were IMP producers; the remaining isolates did not produce carbapenemase.
Conclusions: This is the first Japanese report to demonstrate the significant spread of CRE in both ACHs and LTCHs using an improved selective medium. A coordinated regional approach may help to prevent further spread. (C) 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jhin.2017.07.015

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Perimandibular abscess associated with bisphosphonate-related osteonecrosis of the jaw. Reviewed

Kazuki Ocho, Masaya Iwamuro, Hideharu Hagiya, Soichiro Ibaragi, Fumio Otsuka

Journal of general and family medicine   18 ( 5 )   305 - 306   2017.10

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DOI： 10.1002/jgf2.71

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Genetic characterization of bla(NDM)-harboring plasmids in carbapenem-resistant Escherichia coli from Myanmar Reviewed International journal

Yo Sugawara, Yukihiro Akeda, Noriko Sakamoto, Dan Takeuchi, Daisuke Motooka, Shota Nakamura, Hideharu Hagiya, Norihisa Yamamoto, Isao Nishi, Hisao Yoshida, Kazuhisa Okada, Khwar Nyo Zin, Mya Mya Aye, Kazunori Tonomo, Shigeyuki Hamada

PLOS ONE   12 ( 9 )   e0184720   2017.9

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The bacterial enzyme New Delhi metallo-beta-lactamase hydrolyzes almost all beta-lactam antibiotics, including carbapenems, which are drugs of last resort for severe bacterial infections. The spread of carbapenem-resistant Enterobacteriaceae that carry the New Delhi metallo-beta-lactamase gene, bla(NDM), poses a serious threat to public health. In this study, we genetically characterized eight carbapenem-resistant Escherichia coli isolates from a tertiary care hospital in Yangon, Myanmar. The eight isolates belonged to five multilocus-sequence types and harbored multiple antimicrobial-resistance genes, resulting in resistance against nearly all of the antimicrobial agents tested, except colistin and fosfomycin. Nine plasmids harboring bla(NDM) genes were identified from these isolates. Multiple bla(NDM) genes were found in the distinct Inc-replicon types of the following plasmids: an IncA/C-2 plasmid harboring bla(NDM-1) (n = 1), IncX3 plasmids harboring bla(NDM-4) (n = 2) or bla(NDM-7) (n = 1), IncFII plasmids harboring bla(NDM-4) (n = 1) or bla(NDM-5) (n = 3), and a multireplicon F plasmid harboring bla(NDM-5) (n = 1). Comparative analysis highlighted the diversity of the bla(NDM)-harboring plasmids and their distinct characteristics, which depended on plasmid replicon types. The results indicate circulation of phylogenetically distinct strains of carbapenem-resistant E. coli with various plasmids harboring bla(NDM) genes in the hospital.

DOI： 10.1371/journal.pone.0184720

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PCR-Dipstick Chromatography for Differential Detection of Carbapenemase Genes Directly in Stool Specimens Reviewed International journal

Rathina Kumar Shanmugakani, Yukihiro Akeda, Norihisa Yamamoto, Noriko Sakamoto, Hideharu Hagiya, Hisao Yoshida, Dan Takeuchi, Yo Sugawara, Takuya Kodera, Mitsuo Kawase, Warawut Laolerd, Narong Chaihongsa, Pitak Santanirand, Yoshikazu Ishii, Shigeyuki Hamada, Kazunori Tomono

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY   61 ( 6 )   2017.6

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A PCR-dipstick chromatography technique was designed and evaluated for differential identification of blaNDM, blaKPC, blaIMP, and blaOXA-48 carbapenemase genes directly in stool specimens within 2 h. It is a DNA-DNA hybridization-based detection system where PCR products can be easily interpreted by visual observation without electrophoresis. The PCR-dipstick showed high sensitivity (93.3%) and specificity (99.1%) in directly detecting carbapenemase genes in stool specimens compared with multiplex PCR for genomic DNA of the isolates from those stool specimens.

DOI： 10.1128/AAC.00067-17

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Mycoplasma hominis periaortic abscess following heart-lung transplantation Reviewed International journal

Hideharu Hagiya, Hisao Yoshida, Norihisa Yamamoto, Keigo Kimura, Akiko Ueda, Isao Nishi, Yukihiro Akeda, Kazunori Tomono

TRANSPLANT INFECTIOUS DISEASE   19 ( 3 )   2017.6

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We report the first case of Mycoplasma hominis periaortic abscess after heart-lung transplantation. The absence of sternal wound infection delayed the diagnosis, but the patient successfully recovered with debridement surgeries and long-term antibiotic therapy. Owing to the difficulty in detection and the intrinsic resistance to beta-lactams, M.hominis infections are prone to being misdiagnosed and undertreated. M.hominis should be suspected in cases where conventional microbiological identification and treatment approaches fail.

DOI： 10.1111/tid.12697

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Nosocomial transmission of carbapenem-resistant Klebsiella pneumoniae elucidated by single-nucleotide variation analysis: a case investigation Reviewed International journal

Hideharu Hagiya, Kotaro Aoki, Yukihiro Akeda, Noriko Sakamoto, Norihisa Yamamoto, Hisao Yoshida, Isao Nishi, Yoshikazu Ishii, Kazunori Tomono

INFECTION   45 ( 2 )   221 - 225   2017.4

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Identifying transmission route of antimicrobial-resistant pathogen is essential for appropriate infection control strategy in healthcare facilities. We report the utility of single-nucleotide variation analysis in tracing nosocomial transmission of antimicrobial-resistant pathogens by describing a pseudo-outbreak case of carbapenem-resistant Klebsiella pneumoniae. The present case highlights that infection control strategy should encompass pathological dissection rooms, neglected but potentially highly contaminated places in hospitals.

DOI： 10.1007/s15010-017-0986-3

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Endoscopic Manifestations and Clinical Characteristics of Cytomegalovirus Infection in the Upper Gastrointestinal Tract Reviewed

Masaya Iwamuro, Eisei Kondo, Takehiro Tanaka, Hideharu Hagiya, Seiji Kawano, Yoshiro Kawahara, Fumio Otsuka, Hiroyuki Okada

ACTA MEDICA OKAYAMA   71 ( 2 )   97 - 104   2017.4

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We retrospectively analyzed the cases of 14 patients (9 women, 5 men, mean age: 51.6 years) with cytomegalovirus (CMV) involvement in the esophagus, stomach, and/or duodenum diagnosed at a single center, to determine their endoscopic features and clinical backgrounds. Thirteen patients (92.9%) had hematologic disease; the other had rheumatoid arthritis. Of the former, 12 patients underwent allogeneic hematopoietic stem cell transplantation, and 9 of these patients had graft-versus-host disease (GVHD) before undergoing esophagogastroduodenoscopy (EGD). All 14 patients had been taking one or more immunosuppressive agents including cyclosporine (n=10), corticosteroids (n= 9), mycophenolic acid (n= 6), tacrolimus (n=3), and methotrexate (n=1). Tests for CMV antigenemia were positive in 11 patients (78.6%). EGD examinations revealed esophageal (n=3), gastric (n=9), and duodenal involvement (n=6). Macroscopically, esophageal lesions by CMV infection presented as redness (n=1), erosions (n=1), and ulcers (n=1). Gastric lesions manifested as redness (n=7), erosions (n=3), exfoliated mucosa (n=2), and verrucous erosions (n=1). Mucosal appearances in the duodenum varied: redness (n=2), ulcers (n=2), multiple erosions (n=2), single erosion (n=1), edema (n=1). CMV was detected even in the intact duodenal mucosa (n=1). In conclusion, physicians must recall the relevance of CMV infection when any mucosal alterations exist in the upper gastrointestinal tract of immunosuppressed patients.

DOI： 10.18926/AMO/54977

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Risk factors for Propionibacterium acnes infection after neurosurgery: A case-control study Reviewed International journal

Yuto Haruki, Hideharu Hagiya, Yu Takahashi, Hideyuki Yoshida, Kazuki Kobayashi, Tadato Yukiue, Nobushige Tsuboi, Tetsuhiro Sugiyama

JOURNAL OF INFECTION AND CHEMOTHERAPY   23 ( 4 )   256 - 258   2017.4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Propionibacterium acnes is increasingly known as a causative organism for post-neurosurgical infection; however, no clinical studies have examined the risk factors associated with P. acnes infections. Clinical data obtained from 14 cases of P. acnes infection and 28 controls infected with other pathogens were analyzed. Craniotomy, malignancy, and prolonged duration of operation were significantly associated with the onset of P. acnes infection. No fatal cases were reported. (C) 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2016.10.003

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Development of selective medium for IMP-type carbapenemase-producing Enterobacteriaceae in stool specimens Reviewed International journal

Norihisa Yamamoto, Ryuji Kawahara, Yukihiro Akeda, Rathina Kumar Shanmugakani, Hisao Yoshida, Hideharu Hagiya, Naohiro Hara, Isao Nishi, Satomi Yukawa, Rumiko Asada, Yumi Sasaki, Kazuhiro Maeda, Noriko Sakamoto, Shigeyuki Hamada, Kazunori Tomono

BMC INFECTIOUS DISEASES   17 ( 1 )   229 - 229   2017.3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Identification of carbapenemase-producing Enterobacteriaceae (CPE) in faecal specimens is challenging. This fact is particularly critical because low-level carbapenem-resistant organisms such as IMP-producing CPE are most prevalent in Japan. We developed a modified selective medium more suitable for IMP-type CPE.
Methods: Fifteen reference CPE strains producing different types of beta-lactamases were used to evaluate the commercially available CHROMagar KPC and chromID CARBA as well as the newly prepared MC-ECC medium (CHROMagar ECC supplemented with meropenem, cloxacillin, and ZnSO4) and M-ECC medium ( CHROMagar ECC supplemented with meropenem and ZnSO4). A total of 1035 clinical samples were then examined to detect CPE using chromID CARBA and M-ECC medium.
Results: All tested strains producing NDM-,KPC-, and OXA-48-carbapenemases were successfully cultured in the media employed. Although most of the IMP-positive strains did not grow in CHROMagar KPC, chromID CARBA, or MC-ECC, all tested strains grew on M-ECC. When faecal samples were applied to the media, M-ECC medium allowed the best growth of IMP-type CPE with a significantly higher sensitivity (99.3%) than that of chromID CARBA (13.9%).
Conclusions: M-ECC medium was determined as the most favourable selective medium for the detection of IMP-type CPE as well as other types of CPE.

DOI： 10.1186/s12879-017-2312-1

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Pancreatic Neuroendocrine Tumor Abnormally Secreting Procalcitonin Reviewed International journal

Hideharu Hagiya, Takahiro Matsui, Tetsuhiro Kitamura, Takanori Inoue, Minoru Shigekawa, Hisao Yoshida, Eiichi Morii, Kazunori Tomono

PANCREAS   46 ( 1 )   E7 - E9   2017.1

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DOI： 10.1097/MPA.0000000000000708

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Infective thoracic aortic aneurysm caused by Clostridium difficile after endovascular aortic repair Reviewed International journal

Hideharu Hagiya, Keigo Kimura, Akiko Ueda, Isao Nishi, Norihisa Yamamoto, Hisao Yoshida, Kazunori Tomono

JOURNAL OF INFECTION AND CHEMOTHERAPY   23 ( 1 )   62 - 64   2017.1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Clostridium difficile generally causes enterocolitis by producing pathogenic toxins, while extraintestinal infections with C. difficile are extremely rare. Here we report the first documented case of an infective thoracic aortic aneurysm caused by nontoxic C. difficile that occurred after vascular interventions including endovascular aortic repair. The present case illustrates that endovascular interventions may expose patients to the rare infection by yielding the ischemic intestinal tract as an entry site for the pathogen into the bloodstream and providing an anaerobic environment inside the thrombosed aneurysm. (C) 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2016.08.002

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[Series: Diagnosis at a Glance]. Reviewed

Hagiya H, Thiansukhon E, Akeda Y, Oishi K, Tomono K

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine   106 ( 1 )   127 - 129   2017.1

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Successful treatment with glucocorticoid for secondary Fanconi syndrome caused by sarcoidosis Reviewed International journal

Daisuke Omura, Hideharu Hagiya, Yoshihisa Hanayama, Kou Hasegawa, Hiroshi Morinaga, Atsue Kikuta, Hitomi Kataoka, Fumio Otsuka

MODERN RHEUMATOLOGY   27 ( 3 )   545 - 547   2017

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

A 77-year-old female with renal dysfunction, hypercalcemia, and hypercalciuria was presented. Systemic investigations including renal biopsy showed that the patient had Fanconi syndrome secondary to renal sarcoidosis. Treatment with 25 mg per day of prednisolone was initiated and her condition improved. Complication of Fanconi syndrome in patients with sarcoidosis is extremely rare. Although the pathological mechanism is still unknown, corticosteroid therapy was effective for ameliorating proteinuria, glycosuria, hypercalciuria, and aminoaciduria.

DOI： 10.3109/14397595.2014.1002163

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Paroxysmal Hypertension Induced by an Insulinoma Reviewed

Ko Harada, Yoshihisa Hanayama, Kou Hasegawa, Masaya Iwamuro, Hideharu Hagiya, Ryuichi Yoshida, Fumio Otsuka

INTERNAL MEDICINE   56 ( 4 )   413 - 417   2017

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

Insulinoma is a rare, usually benign, pancreatic neuroendocrine tumor. The clinical features of an insulinoma are fasting hypoglycemia with neuroglycopenic symptoms including confusion and unusual behavior, while hypertension is usually not associated with the disease. We herein report a patient with insulinoma who manifested paroxysmal hypertension and neuroglycopenic symptoms. The possible etiology of hypertension induced by an insulinoma is catecholamine release in response to hypoglycemia, which may cause acute hypertension through activation of the sympatho-adrenal system. This case implies that sustained hyperinsulinemia due to insulinoma can be functionally linked to the induction of paroxysmal hypertension.

DOI： 10.2169/internalmedicine.56.7758

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Hypersensitivity Pneumonitis Caused by a Home Ultrasonic Humidifier Contaminated with Candida guilliermondii Reviewed

Akemi Ando, Hideharu Hagiya, Takahiro Nada, Kosuke Kimura, Koichi Waseda, Kammei Rai, Yoshihisa Hanayama, Fumio Otsuka

INTERNAL MEDICINE   56 ( 22 )   3109 - 3112   2017

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We herein report the first documented case of acute hypersensitivity pneumonitis in which Candida guilliermondii was the possible causative organism. A young Japanese woman presented to our hospital with relapsing respiratory symptoms accompanied by high fever. A detailed interview revealed that the onset of the symptoms occurred shortly after using a humidifier in her home. Her symptoms showed spontaneous improvement soon after admission, and an examination of her bronchoalveolar lavage fluid revealed the specific infiltration of inflammatory cells, which predominantly consisted of lymphocytes. Precipitin testing showed a positive reaction to C. guilliermondii, which was isolated from the home humidifier. Repeated history taking is essential for diagnosing occult respiratory disorders.

DOI： 10.2169/internalmedicine.9055-17

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Tramlines Emerging on a Lower Leg Reviewed

Hideharu Hagiya

INTERNAL MEDICINE   56 ( 15 )   2079 - 2080   2017

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

DOI： 10.2169/internalmedicine.56.8403

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Clinical Characteristics of Stenotrophomonas maltophilia Bacteremia: A Regional Report and a Review of a Japanese Case Series Reviewed

Hirotaka Ebara, Hideharu Hagiya, Yuto Haruki, Eisei Kondo, Fumio Otsuka

INTERNAL MEDICINE   56 ( 2 )   137 - 142   2017

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

Objective Stenotrophomonas maltophilia is an emerging nosocomial pathogen that causes fatal infections in critically ill or immunocompromised patients. S. maltophilia bacteremia (SMB) is a rare condition, and its clinical characteristics in Japanese settings are not well known.
Methods The medical charts of patients with SMB were retrospectively reviewed at two medical facilities (Okayama University Hospital and Tsuyama Chuo Hospital) for seven years. The data were analyzed along with those previously reported from other Japanese facilities.
Result A total of 181 patients (110 men and 71 women) were evaluated. The major underlying diseases included hematologic malignancy (36.5%), solid organ malignancy (25.4%), and neutropenia (31.5%). The recent use of carbapenem was seen in 56.9% of the cases in total, and more than one-third of the patients in our hospitals were treated with carbapenem at the onset of SMB. Of 28 (63.6%) of 44 cases treated for S. maltophilia, those who did not survive were more likely to have been treated with broad-spectrum antibiotics. A multivariate analysis revealed that a higher updated Charlson Comorbidity Index [odds ratio (95% confidence interval), 1.75 (1.11-2.75); p=0.015] and intubation [odds ratio (95% confidence interval), 12.6 (1.62-97.9); p=0.016] were associated with mortality in our cases. Pathogens were often resistant to ceftazidime but susceptible to minocycline, trimethoprim/sulfamethoxazole, and fluoroquinolones. The overall mortality rates within 30 and 90 days were 37.5% and 62.5%, respectively.
Conclusion The clinical characteristics of SMB in Japanese cases were similar to those reported from other countries. Clinicians should be aware that breakthrough infection by S. maltophilia may occur during administration of carbapenem.

DOI： 10.2169/internalmedicine.56.6141

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Novel and Simple Approach to Estimating the Actual Incidence of Blood and Body Fluid Exposure Reviewed International journal

Nori Yoshioka, Matsuo Deguchi, Hideharu Hagiya, Masanori Kagita, Satomi Yukawa, Hiroko Tsukamoto, Hisao Yoshida, Norihisa Yamamoto, Yukihiro Akeda, Yoshiko Nabetani, Ikuhiro Maeda, Yoh Hidaka, Kazunori Tomono

CLINICAL LABORATORY   63 ( 9 )   1481 - 1486   2017

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Background: There is no current way to determine the actual blood and body fluid exposure (BBFE) incidence in hospitals. We propose a simple, reliable, and widely available method for the accurate estimation of BBFE.
Methods: Data for BBFE for healthcare workers between 2006 and 2015 at Osaka University Hospital were retrospectively extracted from the electronic records. Annual positivity of hepatitis C virus (HCV) antibody in the source individuals and overall patient population were calculated over time. We created an estimation formula focusing on the difference in HCV positivity between the source individuals and overall patient population for the actual number of BBFEs. A linear regression model was used to evaluate the temporal change in the reported and estimated BBFEs.
Results: During the study period, 937 BBFEs were reported. HCV positivity between the post-BBFE cohort and overall patient population greatly differed; the incidence ratio ranged from 2.1 to 5.7. The linear regression model revealed that the reported BBFEs did not significantly change during the study period (the slope, 1.315 [95% confidence interval (C.I.): -0.849 to 3.480, p = 0.199]). The annual incidence ratio of the estimated and reported BBFEs significantly reduced over time (the slope, -0.287 [95% C.I.: -0.488 to -0.086, p = 0.011]), indicating that, although the reported number of BBFEs seemed unchanged, the estimated incidence decreased.
Conclusions: We propose a novel and simple approach to estimating the actual incidence of BBFEs in hospitals using the difference in HCV positivity between the post-BBFE cohort and overall patient population.

DOI： 10.7754/Clin.Lab.2017.170340

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Complete genome sequence of systemically disseminated sequence type 8 staphylococcal cassette chromosome mec type IVl community-acquired methicillin-resistant Staphylococcus aureus Reviewed

Junzo Hisatsune, Hideharu Hagiya, Sumiko Shiota, Motoyuki Sugaia

Genome Announcements   5 ( 35 )   2017

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Staphylococcus aureus JH4899, a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate collected from a patient with systematically disseminated infection, is classified as sequence type 8 and carries the staphylococcal cassette chromosome mec type IVl (SCCmecIVl). It produces TSST-1, SEC, a newly discovered enterotoxin (SE1), and epidermal cell differentiation inhibitor A (EDIN-A). Here, we present the complete genome sequence of the chromosome and a plasmid harboring the se1 and ednA genes.

DOI： 10.1128/genomeA.00852-17.

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Complete genome sequence of systemically disseminated sequence type 8 staphylococcal cassette chromosome mec type IVl community-acquired methicillin-resistant Staphylococcus aureus Reviewed International journal

Junzo Hisatsune, Hideharu Hagiya, Sumiko Shiota, Motoyuki Sugaia

Genome Announcements   5 ( 35 )   2017

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Society for Microbiology  

Staphylococcus aureus JH4899, a community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) isolate collected from a patient with systematically disseminated infection, is classified as sequence type 8 and carries the staphylococcal cassette chromosome mec type IVl (SCCmecIVl). It produces TSST-1, SEC, a newly discovered enterotoxin (SE1), and epidermal cell differentiation inhibitor A (EDIN-A). Here, we present the complete genome sequence of the chromosome and a plasmid harboring the se1 and ednA genes.

DOI： 10.1128/genomeA.00852-17.

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Herpes zoster laryngitis in a patient treated with fingolimod Reviewed International journal

Hideharu Hagiya, Hisao Yoshida, Mikito Shimizu, Daisuke Motooka, Shota Nakamura, Tetsuya Iida, Norihisa Yamamoto, Yukihiro Akeda, Kazunori Tomono

JOURNAL OF INFECTION AND CHEMOTHERAPY   22 ( 12 )   830 - 832   2016.12

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Development of treatment with immunomodulatory agents has improved prognosis of various autoimmune-related diseases. A sphingosin-1-phosphate receptor modulator, or fingolimod, is the first licensed oral drug for relapsing-remitting multiple sclerosis. The agent reduces circulating lymphocytes by trapping T cells in lymph nodes, possibly leading to reactivation of latent viruses. A 41-year-old Japanese woman who had been treated with fingolimod for 2 years presented with unilateral sore throat. Laryngoscopy revealed exudates unilaterally emerging on the left side of her supraglottic region. Serum level of the varicella zoster virus (VZV)-specific IgG was markedly elevated, and a result of genome sequence using the exudates demonstrated VZV as a possible causative pathogen. Fingolimod therapy was discontinued and the patient was successfully treated with intravenous acyclovir. This is the first reported case of fingolimod-associated herpes zoster laryngitis, in which the local VZV reactivation was demonstrated by next-generation sequencing technology. The present case highlights that the occurrence of VZV reactivation should be recalled in any patients undergoing fingolimod therapy. (C) 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2016.07.011

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Kikuchi-Fujimoto Disease Complicated with Reactive Hemophagocytic Lymphohistiocytosis Reviewed

Masatake Nishiwaki, Hideharu Hagiya, Toru Kamiya

ACTA MEDICA OKAYAMA   70 ( 5 )   383 - 388   2016.10

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Kikuchi-Fujimoto disease (KFD) is a benign cause of self-limiting subacute necrotizing lymphadenitis. KFD is rarely complicated with reactive hemophagocytic lymphohistiocytosis (HLH), and the clinical features of the simultaneous occurrence of these conditions are uncertain. A 30-year-old Japanese man with a persistent fever and sore throat presented to our hospital for treatment. Laboratory analysis showed bicytopenia, and radiological studies showed systemic lymphadenopathy accompanied by splenomegaly. A bone marrow examination showed hemophagocytic macrophages, suggesting HLH. Malignant lymphoma was suspected as a possible underlying disease, but the histology of the lymph nodes led to a final diagnosis of KFD and treatment with prednisolone (1 mg/kg/day), resulting in clinical improvement. This case highlighted the importance and difficulty of differentiating KFD from malignant lymphoma as an underlying condition of HLH. The literature review showed that patients with HLH-associated KFD may have higher serum ferritin and lactate dehydrogenase levels compared to typical KFD cases. Definite diagnosis based on pathological examination is essential for a better understanding of this rare disease. The presence of systemic lymphadenopathy does not exclude the possibility of KFD. This case serves to remind physicians that KFD is a potential etiology of HLH.

DOI： 10.18926/AMO/54597

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Non-nosocomial healthcare-associated left-sided Pseudomonas aeruginosa endocarditis: a case report and literature review Reviewed International journal

Hideharu Hagiya, Takeshi Tanaka, Kohei Takimoto, Hisao Yoshida, Norihisa Yamamoto, Yukihiro Akeda, Kazunori Tomono

BMC INFECTIOUS DISEASES   16 ( 1 )   431 - 431   2016.8

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Background: With the development of invasive medical procedures, an increasing number of healthcare-associated infective endocarditis cases have been reported. In particular, non-nosocomial healthcare-associated infective endocarditis in outpatients with recent medical intervention has been increasingly identified.
Case presentation: A 66-year-old man with diabetes mellitus and a recent history of intermittent urethral self-catheterization was admitted due to a high fever. Repeated blood cultures identified Pseudomonas aeruginosa, and transesophageal echocardiography uncovered a new-onset severe aortic regurgitation along with a vegetative valvular structure. The patient underwent emergency aortic valve replacement surgery and was successfully treated with 6 weeks of high-dose meropenem and tobramycin. Historically, most cases of P. aeruginosa endocarditis have occurred in the right side of the heart and in outpatients with a history of intravenous drug abuse. In the case presented, the repeated manipulations of the urethra may have triggered the infection. Our literature review for left-sided P. aeruginosa endocarditis showed that non-nosocomial infection accounted for nearly half of the cases and resulted in fatal outcomes as often as nosocomial cases. A combination therapy with anti-pseudomonal beta-lactams or carbapenems and aminoglycosides may be the preferable treatment. Medical treatment alone may be effective, and surgical treatment should be carefully considered.
Conclusions: We presented a rare case of native aortic valve endocarditis caused by P. aeruginosa. This case illustrates the importance of identifying the causative pathogen(s), especially for outpatients with a recent history of medical procedures.

DOI： 10.1186/s12879-016-1757-y

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Necrotizing soft tissue infection caused by Serratia marcescens: A case report and literature review Reviewed International journal

Hideharu Hagiya, Masahiro Ojima, Takeshi Yoshida, Takahiro Matsui, Eiichi Morii, Kazuaki Sato, Shinichiro Tahara, Hisao Yoshida, Kazunori Tomono

JOURNAL OF INFECTION AND CHEMOTHERAPY   22 ( 5 )   335 - 338   2016.5

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A 64-year-old man with advanced liver cirrhosis was transferred to an emergency center due to septic shock and markedly inflamed left leg. Under a clinical diagnosis of necrotizing soft tissue infection (NSTI), the patient undertook intensive therapy but died 25 h after arrival. The pathogenic organism, Serratia marcescens, was later isolated from blood and soft tissue cultures. NSTI is very rarely associated with S. marcescens. A literature review showed that only 16 such cases, including our case, have been reported to date. Our case is the first evidence of an S. marcescens NSTI in a patient with liver cirrhosis. S. marcescens NSTI has an extremely high mortality rate; total mortality and mortality in cases involving the extremities were 75% (12 of 16 cases) and 83.3% (10 of 12 cases), respectively. Physicians need to be aware that S. marcescens can induce fatal infections in community patients. (C) 2015, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2015.11.013

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Capnocytophaga ochracea-related Bacterium Bacteremia in a Hypertrophic Cardiomyopathy Patient without Neutropenia Reviewed

Shimpei Ito, Hideharu Hagiya, Keigo Kimura, Isao Nishi, Hisao Yoshida, Hidetaka Kioka, Tomohito Ohtani, Osamu Yamaguchi, Kazuaki Tanabe, Kazunori Tomono, Yasushi Sakata

INTERNAL MEDICINE   55 ( 18 )   2731 - 2735   2016

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Gram-negative fusiform rods were detected in a blood culture obtained from a 63-year-old man who had been hospitalized for a long duration for severe heart failure. Although the organism could not be identified using a conventional method, it was finally identified as a bacterium of the Capnocytophaga ochracea group based on the results of biochemical testing, 16S rRNA sequencing and a matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis. Although neutropenic patients with poor oral hygiene are exclusively vulnerable to Capnocytophaga bacteremia, this case was unique because such predisposing conditions were not noted. A multi-centered investigation is warranted for a better understanding of this clinically rare, but potentially pathogenic organism.

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Emergence of Daptomycin-Resistant Staphylococcus aureus during Treatment Reviewed

Hideharu Hagiya, Yuto Haruki, Taeko Uchida, Tomoko Wada, Sumiko Shiota, Tomoharu Ishida, Hiroko Ogawa, Tomoko Murase, Fumio Otsuka

INTERNAL MEDICINE   55 ( 1 )   73 - 78   2016

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A 68-year-old man with persistent bacteremia accompanying a large iliopsoas abscess, vertebral osteomyelitis, discitis and central venous port infection caused by methicillin-resistant Staphylococcus aureus (MRSA) was admitted to our hospital. During the course of treatment, the emergence of a daptomycin (DAP)-resistant MRSA strain was confirmed; the minimum inhibitory concentration was 1 to 2 mu g/mL for vancomycin and more than 1 mu g/mL for DAP. Although the bacterial cell wall was not significantly thickened, an increased positive surface charge and single-nucleotide polymorphism within mprF have been confirmed in DAP-resistant strains. Still rare, but clinicians need to be cautious of the emergence of DAP-resistant MRSA during treatment.

DOI： 10.2169/internalmedicine.55.4763

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Hypoparathyroidism Solely Manifesting Otological Symptoms Reviewed

Tokiko Urabe, Hideharu Hagiya, Eri Nakamura, Fumio Otsuka

INTERNAL MEDICINE   55 ( 2 )   211 - 212   2016

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DOI： 10.2169/internalmedicine.55.5347

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Reactivation of Human Herpes Virus-6 in the Renal Tissue of a Patient with Drug-induced Hypersensitivity Syndrome/Drug Rash with Eosinophilia and Systemic Symptoms (DIHS/DRESS) Reviewed

Hideharu Hagiya, Masaya Iwamuro, Takehiro Tanaka, Kou Hasegawa, Yoshihisa Hanayama, Maya Kimura, Fumio Otsuka

INTERNAL MEDICINE   55 ( 13 )   1769 - 1774   2016

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A 74-year-old man who had been administered trimethoprim-sulfamethoxazole for three weeks suffered from drug-induced hypersensitivity syndrome/drug rash with eosinophilia and systemic symptoms (DIHS/DRESS). In the early stage of the clinical course, he developed renal dysfunction. A renal biopsy showed granulomatous tubulointerstitial nephritis accompanying the proliferation of human herpes virus ( HHV)-6 in tubular epithelial cells. With corticosteroid therapy, the systemic rash and renal function gradually improved. The present patient is the second case of DIHS/DRESS demonstrating a possible reactivation of HHV-6 in the renal tissue. The clinical role of viral reactivation in DIHS/DRESS must be further elucidated.

DOI： 10.2169/internalmedicine.55.6287

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Olecranon Osteomyelitis Caused by Mycobacterium chelonae Reviewed

Hideharu Hagiya, Misa Hayashi, Ichiro Katayama, Kazunori Tomono

INTERNAL MEDICINE   55 ( 13 )   1825 - 1825   2016

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DOI： 10.2169/internalmedicine.55.6490

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A Necrotized Eyelid Reviewed

Hideharu Hagiya, Ekkachai Thiansukhon, Yukihiro Akeda, Kazunori Tomono

INTERNAL MEDICINE   55 ( 15 )   2121 - 2121   2016

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DOI： 10.2169/internalmedicine.55.6574

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Refractory chyluria due to filariasis Reviewed International journal

Hideharu Hagiya, Fumio Otsuka

INFECTION   43 ( 6 )   785 - 786   2015.12

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DOI： 10.1007/s15010-015-0804-8

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Pheochromocytoma Manifesting Persistent Right Shoulder Pain and Hypochondralgia

Hideharu Hagiya, Eri Nakamura, Tomohiro Terasaka, Kou Hasegawa, Kikuko Asano, Takahiro Nada, Kosuke Kimura, Koichi Waseda, Yoshihisa Hanayama, Fumio Otsuka

JOURNAL OF GENERAL AND FAMILY MEDICINE   16 ( 4 )   292 - 296   2015.12

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We report a 42-year-old female who initially complained of sub-acute onset of right upper quadrant abdominal pain with right shoulder pain. A CT scan incidentally revealed an adrenal tumor, and a final diagnosis of pheochromocytoma was made on the basis of endocrinological examinations. Symptomatically, the pheochromocytoma in our patient mimicked a hepato-biliary disease by presenting abdominal pain accompanying right shoulder pain that was assumed to be referred pain via the right phrenic nerve. Physicians may need to consider the possibility of pheochromocytoma in patients with abdominal symptoms.

DOI： 10.14442/jgfm.16.4_292

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Predominance of PCR-ribotypes, 018 (smz) and 369 (trf) of Clostridium difficile in Japan: a potential relationship with other global circulating strains? Reviewed International journal

Mitsutoshi Senoh, Haru Kato, Tadashi Fukuda, Akiko Niikawa, Yoshiko Hori, Hideharu Hagiya, Yoichiro Ito, Hiroshi Miki, Yoshifumi Abe, Kiyoshi Furuta, Hideki Takeuchi, Hirokazu Tajima, Harumi Tominaga, Hideyuki Satomura, Hideaki Kato, Sayuri Morita, Ai Tanada, Toshinori Hara, Miki Kawada, Yuka Sato, Masahiko Takahashi, Akiko Higuchi, Tomoko Nakajima, Yukiko Wakamatsu, Masahiro Toyokawa, Akiko Ueda, Paul Roberts, Fabio Miyajima, Keigo Shibayamal

JOURNAL OF MEDICAL MICROBIOLOGY   64 ( 10 )   1226 - 1236   2015.10

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Global spread and evolutionary links of an epidemic Clostridium difficile strain (PCR-ribotype 027) have been noted in recent decades. However, in Japan, no outbreaks caused by type 027 have been reported to date. A total of 120 C. difficile isolates from patients at 15 hospitals during non-outbreak seasons between 2011 and 2013 as well as 18 and 21 isolates collected from two hospitals in 2010 and 2009, respectively, in outbreak periods in Japan, were examined. Among these 120 isolates, Japan-ribotypes smz and ysmz (subtype variant of smz) were the most predominant (39.2 %) followed by Japan-ribotype trf (15.8 %). Types smz/ysmz and trf were also concurrently predominant at two hospitals in the outbreak settings. Out of the five binary toxin-positive isolates observed, only one was PCR-ribotype 027 and another PCR-ribotype 078. Type smz was later found to correspond to PCR-ribotype 018. High rates of resistance against gatifloxacin, moxifloxacin, erythromycin and clindamycin were observed in the PCR-ribotype 018 isolates. Interestingly, all trf isolates were toxin A-negative, toxin B-positive, but they did not correspond to PCR-ribotype 017, thus being assigned a new ribotype (PCR-ribotype 369). In conclusion, PCR-ribotypes 018 (smz) and 369 (trf) were identified as major circulating strains in both outbreak and non-outbreak settings in Japan. Given their epidemiological relevance, molecular investigations are warranted to clarify potential evolutionary links with related strains found elsewhere, such as PCR-ribotypes 018 and 017 from Europe and North America.

DOI： 10.1099/jmm.0.000149

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Cytomegalovirus as an Insidious Pathogen Causing Duodenitis Reviewed

Hideharu Hagiya, Masaya Iwamuro, Takehiro Tanaka, Yoshihisa Hanayama, Fumio Otsuka

ACTA MEDICA OKAYAMA   69 ( 5 )   319 - 323   2015.10

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A 60-year-old woman with rheumatoid arthritis treated with methotrexate for a decade complained of slight epigastric discomfort. A positive cytomegalovirus (CMV) antigenemia test indicated the probability of CMV-related gastrointestinal infection, for which esophagogastroduodenoscopy was performed. Endoscopic findings showed a non-specific duodenal mucosal lesion; however, pathological investigation revealed evidence of CMV duodenitis. There is scarce information on the clinical and pathological features of CMV-related duodenitis, likely due to its low prevalence. CMV infection in the upper gastrointestinal tract should be considered as a differential diagnosis in high-risk individuals, particularly those with symptoms relating to the digestive system. Biopsy examinations are preferable for the definitive diagnosis of CMV gastrointestinal infection, even without specific endoscopic features.

DOI： 10.18926/AMO/53679

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Investigation of Intravenous Azithromycin Treatment Safety When Reducing Solvent for Intensive Care Unit Patients Reviewed

Yuto Haruki, Hideharu Hagiya, Akiko Sakuma, Mai Haruki, Yasue Oka, Tetsuhiro Sugiyama, Yasuhiro Kawakami, Sachiyo Kondo

YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN   135 ( 8 )   987 - 990   2015.8

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Intravenous azithromycin (AZM) was approved for use in December 2011 in Japan. In general, intravenous AZM injections are diluted to 1 mg/mL, with a total infusion volume of 500 mL to avoid phlebitis. Patients in intensive care units (ICUs) require small infusion volumes. We retrospectively evaluated the total AZM infusion volume in 65 ICU patients receiving AZM treatment from December 2011 to August 2014. Thirteen patients (20.0%) received a reduced volume [100 mL (5 mg/mL) or 250 mL (2 mg/mL)] using an infusion pump over 2 h. No peripheral phlebitis was observed in any patient. Based on this result, it is assumed that AZM can be safely administered to ICU patients even though the volume of solvent is reduced. AZM is widely recommended for the treatment of community-acquired respiratory infections and is used in patients with severe infections. Further investigation is required in additional patients to understand the effects of AZM volume reduction in greater detail.

DOI： 10.1248/yakushi.15-00003

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How can you manage your patients without 'breakpoint'? Reviewed International journal

Hideharu Hagiya

JOURNAL OF CHEMOTHERAPY   27 ( 3 )   193 - 194   2015.6

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DOI： 10.1179/1973947814Y.0000000196

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Atypical Onset of Eosinophilic Granulomatosis with Polyangitis in a Patient with Long-term Well-controlled Bronchial Asthma

Satoshi Akao, Hideharu Hagiya, Kou Hasegawa, Takahiro Nada, Eri Nakamura, Kosuke Kimura, Koichi Waseda, Yoshihisa Hanayama, Kentaro Deguchi, Fumio Otsuka

JOURNAL OF GENERAL AND FAMILY MEDICINE   16 ( 2 )   99 - 102   2015.6

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Eosinophillic glanuromatosis with polyangitis (EGPA) usually occurs in patients with a recent history (usually less than 10 years) of uncontrolled bronchial asthma. Here we describe a case of EGPA that occurred in a 68-year-old female who had well-controlled bronchial asthma for 17 years. A leukotriene receptor antagonist that had been prescribed one week before onset might have triggered the disease. Our case shows that there is a wide spectrum of clinical characteristics of EGPA, making diagnosis difficult in a primary care setting.

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No blood culture examinations during off-hours? Reviewed

Hideharu Hagiya

BRAZILIAN JOURNAL OF INFECTIOUS DISEASES   19 ( 3 )   330 - 331   2015.5

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DOI： 10.1016/j.bjid.2015.01.002

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Complication of Chronic Eosinophilic Pneumonia in an Elderly Patient with Sjogren Syndrome Reviewed

Koichi Waseda, Hideharu Hagiya, Yoshihisa Hanayama, Tomohiro Terasaka, Kosuke Kimura, Takao Tsuzuki, Kou Hasegawa, Takahiro Nada, Eri Nakamura, Kazutoshi Murakami, Eisei Kondo, Fumio Otsuka

ACTA MEDICA OKAYAMA   69 ( 2 )   123 - 127   2015.4

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An 81-year-old Japanese male with primary Sjogren syndrome (pSS) developed a low-grade fever and productive cough which were refractory to antibiotic therapy. Based on the high level of eosinophils observed in his bronchial alveolar lavage, he was diagnosed with chronic eosinophilic pneumonia (CEP) and successfully treated by oral prednisolone. Interstitial lung diseases associated with pSS (pSS-ILDs) usually present as nonspecific interstitial pneumonia or usual interstitial pneumonia; therefore, the present case is extremely unique in that the patient's condition was complicated with CEP. A diagnosis of advanced gallbladder cancer was made in the patient's clinical course, suggesting the advisability of a whole-body workup in cases of pSS, especially in elderly patients.

DOI： 10.18926/AMO/53342

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A Paraganglioma in a Hypertensive Patient with Unilateral Renal Hypoplasia Reviewed

Tomohiro Terasaka, Hideharu Hagiya, Kosuke Kimura, Takahiro Nada, Eri Nakamura, Yoshihisa Hanayama, Hitoshi Sugiyama, Yasuyuki Kobayashi, Hiroyuki Yanai, Fumio Otsuka

ACTA MEDICA OKAYAMA   69 ( 2 )   119 - 122   2015.4

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We report the case of a 46-year-old hypertensive Japanese female with renal insufficiency related to unilateral renal hypoplasia. The patient was found to have developed paraganglioma in the retroperitoneal space over a 5-year period. Catecholamine-producing tumors are not usually recognized as conditions associated with renal hypoplasia. Our long-term observation of the patient eventually led us to the diagnosis of paraganglioma. In hypertensive patients with chronic kidney disease, not only the renin-angiotensin-aldosterone system but also catecholamine activity may be involved, particularly in the patients whose cases are complicated with unilateral renal hypoplasia.

DOI： 10.18926/AMO/53341

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Why not performing susceptibility test for trimethoprim-sulphamethoxazole? Reviewed International journal

Hideharu Hagiya

JOURNAL OF CHEMOTHERAPY   27 ( 2 )   124 - 125   2015.2

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DOI： 10.1179/1973947814Y.0000000215

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Lemierre syndrome involving external jugular vein. Reviewed International journal

Hagiya H, Haruki Y, Otsuka F

Acute medicine & surgery   2 ( 1 )   64 - 68   2015.1

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Case: A 74-year-old woman with a week-long history of cold symptoms was diagnosed with Lemierre syndrome that involved her left external jugular vein. Outcome: The patient was successfully treated with 4 weeks of antibiotics and anticoagulant treatment. Typical cases of Lemierre syndrome involve only the internal jugular vein. The external jugular vein is anatomically distant from the pharyngolaryngeal space and usually does not receive blood or lymphatic flow from there. Thus, Lemierre syndrome ordinarily does not involve the external jugular vein and clinical characteristics of external jugular vein-involving Lemierre syndrome have not been uncovered, mainly due to its rarity. Based on our review, it would not much differ from those of typical cases. Conclusion: Considering the potential severity and mortality, more attention should be paid to this potentially fatal disease that may demonstrate atypical manifestation, as shown in this case. Accumulation of cases would be needed for further understanding.

DOI： 10.1002/ams2.61

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Klebsiella oxytoca-producing IMP-1 Detected as the First Strain of Carbapenem-resistant Enterobacteriaceae in Our Hospital Reviewed

Hideharu Hagiya, Hiroko Ogawa, Yusuke Takahashi, Akira Yamamoto, Fumio Otsuka

INTERNAL MEDICINE   54 ( 22 )   2939 - 2941   2015

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We herein report a case of Klebsiella oxytoca-producing IMP-1 that was detected as a first isolate of carbapenem-resistant Enterobacteriaceae (CRE) at our facility. Since K. oxytoca is an uncommon strain for CRE, we speculated that the resistant organism had already spread out inside the hospital. Metallo-beta-lactamases promotes antibiotic resistance in Enterobacteriaceae, which potentially yields problematic issues in clinical settings. Active surveillance of antibiotic resistant strains is important and should be repeatedly highlighted. Furthermore, appropriate methods should be established to detect highly resistant strains.

DOI： 10.2169/internalmedicine.54.4965

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A Nephrostomy-associated Urinary Tract Infection Caused by Elizabethkingia meningoseptica Reviewed

Hideharu Hagiya, Hiroko Ogawa, Yusuke Takahashi, Kou Hasegawa, Masaya Iwamuro, Fumio Otsuka

INTERNAL MEDICINE   54 ( 24 )   3233 - 3236   2015

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We report a case of nephrostomy-associated urinary tract infection caused by Elizabethkingia meningoseptica that occurred in a patient with retroperitoneal fibrosis. Though conventional identification methods failed to detect the causative organism, it was identified on the basis of the complete sequencing of 16S rRNA. Four weeks of levofloxacin and minocycline administration successfully eradicated the infection. E. meningoseptica rarely causes urinary tract infections, and we believe that this is the first such case in which the isolate was genetically confirmed. The accurate identification of the organism is necessary for the provision of appropriate treatment and to obtain a better understanding of its epidemiology and pathogenicity.

DOI： 10.2169/internalmedicine.54.4998

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Efficacy of Direct Peripheral Blood Smears in Diagnosing Necrotizing Fasciitis Caused by Streptococcus pyogenes Reviewed

Hideharu Hagiya, Chiaki Kobatake, Naoki Morimoto

INTERNAL MEDICINE   54 ( 5 )   543 - 543   2015

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DOI： 10.2169/internalmedicine.54.3392

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Disseminated Streptococcal Endophthalmitis in Two Diabetic Patients Reviewed

Hideharu Hagiya, Kotaro Aoki, Kazuhiro Tateda, Fumio Otsuka

INTERNAL MEDICINE   54 ( 10 )   1317 - 1318   2015

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DOI： 10.2169/internalmedicine.54.4134

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Eagle's Syndrome Manifesting as Chronic Swallowing Pain Reviewed

Hideharu Hagiya, Koichi Waseda, Hiroko Ogawa, Fumio Otsuka

INTERNAL MEDICINE   54 ( 10 )   1321 - 1321   2015

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DOI： 10.2169/internalmedicine.54.4262

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Relapsing Polychondritis Followed Up with FDG-PET Reviewed

Hideharu Hagiya, Koichi Waseda, Fumio Otsuka

INTERNAL MEDICINE   54 ( 13 )   1675 - 1676   2015

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DOI： 10.2169/internalmedicine.54.3752

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Tetanus in a 19-year-old Japanese Woman Reviewed

Hideharu Hagiya, Takahiro Hirayama, Toyomu Ugawa, Fumio Otsuka

INTERNAL MEDICINE   54 ( 14 )   1825 - 1825   2015

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DOI： 10.2169/internalmedicine.54.4404

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Infective Internal Iliac Artery Aneurysm Caused by Campylobacter fetus Reviewed

Hideharu Hagiya, Hiroko Ogawa, Yusuke Takahashi, Kou Hasegawa, Yoshihisa Hanayama, Fumio Otsuka

INTERNAL MEDICINE   54 ( 16 )   2021 - 2024   2015

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A 67-year-old man with a persistent high fever was diagnosed to have an infective aneurysm in his left internal iliac artery. A blood culture detected a gram-negative spiral rod that was first identified as Campylobacter fetus subsp. venerealis based on a matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS) analysis. However, the strain was finally confirmed to be Campylobacter fetus subsp. fetus based on a genetic analysis. The infection was successfully treated with emergency resection of the aneurysm, followed by 4 weeks of antibiotic therapy. Involvement of the peripheral artery is uncommon in cases of C. fetus-infective aneurysm. To figure out the epidemiology and pathogenicity of C. fetus infection, the accurate identification of the responsible organisms is essential.

DOI： 10.2169/internalmedicine.54.4845

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Pyogenic Spondylitis and Diskitis Caused by Helicobacter cinaedi in an Immunocompetent Adult Patient Reviewed

Yuto Haruki, Hideharu Hagiya, Toshiyuki Hashimoto, Takayoshi Miyake, Tomoko Murase, Akane Matsuo, Tetsuhiro Sugiyama, Sachiyo Kondo

INTERNAL MEDICINE   54 ( 18 )   2415 - 2418   2015

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We herein describe the first reported case of pyogenic spondylitis and diskitis caused by Helicobacter cinaedi. The results of magnetic resonance imaging and the histology of biopsied tissue were suggestive of acute infection at the lumbar spine. The pathogen was obtained by a blood culture examination and identified by 16S rRNA analysis. Eight weeks of antibiotics therapy resulted in a good clinical course. H. cinaedi infections have been increasingly reported in recent years, but the pathogen's epidemiological and pathological characteristics are still unclear. One of the difficulties in understanding the pathogenesis of H. cinaedi has been the challenges in cultivating the pathogen. Novel strategies for the diagnosis of H. cinaedi must be developed.

DOI： 10.2169/internalmedicine.54.4726

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Neurosyphilis Is a Long-forgotten Disease but Still a Possible Etiology for Dementia Reviewed

Hideharu Hagiya, Kentaro Deguchi, Kiyohiro Kawada, Fumio Otsuka

INTERNAL MEDICINE   54 ( 21 )   2769 - 2773   2015

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We herein report a heterosexual Japanese man in his forties who had been suffering from advanced dementia and personality change for 4 years. Positive results of a serological test for syphilis, Treponema pallidum hemagglutination assay, and fluorescent treponemal antibody-absorption test of both serum and cerebral spinal fluid led to the diagnosis of neurosyphilis. Jarisch-Herxheimer reaction was seen shortly after the first dose of penicillin was administered to the patient. His cognitive function did not recover after treatment. The incidence of syphilis has been reported to be increasing. Neurosyphilis should not be overlooked as an etiology for progressive dementia even in this post-antibiotic era.

DOI： 10.2169/internalmedicine.54.4956

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Actinomyces turicensis Bacteremia Secondary to Pyometra Reviewed

Hideharu Hagiya, Hiroko Ogawa, Yusuke Takahashi, Kosuke Kimura, Kan Hasegawa, Fumio Otsuka

INTERNAL MEDICINE   54 ( 21 )   2775 - 2777   2015

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We herein present a rare case of Actinomyces turicensis bacteremia that was caused by pyometra. The patient was successfully treated with transvaginal drainage and antibiotic therapy. A literature review in MEDLINE showed that there have been only 8 previously reported cases of A. turicensis bacteremia. This infection frequently occurs in patients with visceral abscesses, and blood culture examinations usually reveal a polymicrobial pattern. However, the prognosis of such patients has been reported to generally be benign. Due to difficulties in performing bacterial identification and the wide-spectrum clinical pictures associated with this bacteremia, no comprehensive understanding of the clinical features of each Actinomyces species has yet been established.

DOI： 10.2169/internalmedicine.54.4637

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Myopathy and Eosinophilic Pneumonia Coincidentally Induced by Treatment with Daptomycin Reviewed

Hideharu Hagiya, Kou Hasegawa, Kikuko Asano, Tomohiro Terasaka, Kosuke Kimura, Takahiro Nada, Eri Nakamura, Koichi Waseda, Yoshihisa Hanayama, Fumio Otsuka

INTERNAL MEDICINE   54 ( 5 )   525 - 529   2015

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A 34-year-old man with 22q11.2 deletion syndrome (DiGeorge syndrome) concurrently suffered from myopathy and eosinophilic pneumonia shortly after receiving daptomycin (DAP) for right-sided infective endocarditis. The simultaneous occurrence of these phenomena in relation to DAP therapy has not been previously well described. An allergic reaction was suspected as a possible etiology of these DAP-related complications. This case highlights the need for close observation in order to detect both musculoskeletal and respiratory disorders from the start of DAP therapy. Physicians should pay more attention to this new drug, which is expected to be frequently used in various clinical settings.

DOI： 10.2169/internalmedicine.54.3397

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Clinical ineffectiveness of latamoxef for Stenotrophomonas maltophilia infection Reviewed International journal

Hideharu Hagiya, Ken Tasaka, Toshiaki Sendo, Fumio Otsuka

INFECTION AND DRUG RESISTANCE   8   353 - 357   2015

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Objectives: Stenotrophomonas maltophilia shows wide-spectrum resistance to antimicrobials and causes various infections in immunocompromised or critically ill patients with high mortality. In this era of antibiotics resistance, a revival of old antibiotics is now featured. We examined the clinical usefulness of latamoxef (LMOX) for the treatment of S. maltophilia infection. Patients and methods: The observational study was retrospectively performed at Okayama University Hospital (Okayama, Japan) from January 2011 to December 2013. LMOX was administered to 12 patients with S. maltophilia infection, with eleven of those patients being admitted to the intensive care unit. Results: Underlying conditions of the patients included postoperation, hematological transplantation, hepatic transplantation, and burn. Major infectious foci were surgical site infection (six cases), respiratory infection (four cases), blood stream infection (three cases), and burn site infection (one case). The doses of LMOX administered ranged from 1 g/d to 3g d for ten adult patients and from 40 mg/kg/ d to 80 mg/kg/d for two pediatric patients. Microbiologic failure was seen in five (41.7%) of 12 cases, and 30-day and hospital mortality rates were 25% and 50%, respectively. Minimum inhibitory concentrations of LMOX were higher in the deceased group (4-64 mu g/mL) than in the surviving group (1-4 mu g/ mL). Conclusion: LMOX treatment is not recommended for the treatment of S. maltophilia infection. Further investigation would be needed before its clinical use.

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Ct visualising infective vegetation Reviewed International journal

Hideharu Hagiya, Kou Hasegawa, Kikuko Asano, Fumio Otsuka

BMJ Case Reports   2014   1 - 2   2014.12

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DOI： 10.1136/bcr-2014-207572

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Aortic vascular graft infection caused by Cardiobacterium valvarum: A case report Reviewed International journal

Hideharu Hagiya, Susumu Kokeguchi, Hiroko Ogawa, Tomohiro Terasaka, Kosuke Kimura, Koichi Waseda, Yoshihisa Hanayama, Kaori Oda, Hisatoshi Mori, Toru Miyoshi, Fumio Otsuka

JOURNAL OF INFECTION AND CHEMOTHERAPY   20 ( 12 )   804 - 809   2014.12

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A 53-year-old man with a past medical history of total arch replacement surgery and severe aortic regurgitation presented with a 1-month history of persistent general malaise, anorexia, body weight loss and night sweats. His recent history included gingival hyperplasia for 6 years, gingivitis after tooth extraction 3 years before, prolonged inflammatory status for 4 months, fundal hemorrhage and leg tenderness for 2 months. A pathogen was detected from blood culture, but conventional microbiological examination failed to identify the pathogen. The organism was eventually identified as Cardiobacterium valvarum by 16S rRNA analysis, and the patient was diagnosed with infective endocarditis and prosthetic vascular graft infection. The patient received intravenous antibiotic therapy using a combination of ceftriaxone and levofloxacin for 5 weeks and was discharged with a good clinical course.
C. valvarum is a rare human pathogen in clinical settings. Only 10 cases have been reported to date worldwide, and therefore, the clinical characteristics of C. valvarum infection are not fully known. This is a first well-described case of C. valvarum infection in Japan, and further, a first report of aortic prosthetic vascular graft infection worldwide. Identification of C. valvarum is usually difficult due to its phenotypic characteristics, and molecular approaches would be required for both clinicians and microbiologists to facilitate more reliable diagnosis and uncover its clinical picture more clearly. (C) 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2014.07.008

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Reverse transcription polymerase chain reaction-based method for selectively detecting vegetative cells of toxigenic Clostridium difficile Reviewed International journal

Mitsutoshi Senoh, Haru Kato, Tomoko Murase, Hideharu Hagiya, Yasuaki Tagashira, Tadashi Fukuda, Masaaki Iwaki, Akihiko Yamamoto, Keigo Shibayama

MICROBIOLOGY AND IMMUNOLOGY   58 ( 11 )   615 - 620   2014.11

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The laboratory diagnostic methods for Clostridium difficile infection (CDI) include toxigenic culture, enzyme immunoassays (EIAs) to detect the toxins of C. difficile, and nucleic acid amplification tests (NAATs) to detect C. difficile toxin genes, but each of these methods has disadvantages; toxigenic cultures require a long time to produce results, EIAs have low sensitivity, and NAATs that target DNA cannot distinguish vegetative cells from spores and dead cells. Here we report a new detection method that uses reverse transcription polymerase chain reaction to target the toxin-gene transcripts. This method was able to specifically detect the vegetative cells of toxigenic C. difficile in fecal samples in spike tests, with a minimum detection limit of 5x10(2) colony-forming units per 100mg of stool specimen. The performance of this method was also demonstrated in a pilot scale evaluation using clinical fecal specimens, which showed that this method may be more sensitive than EIA and requires a shorter time than toxigenic culture. This method could potentially be applied in the clinical laboratory to detect C. difficile in fecal specimens. The ability of this method to discriminate the presence of vegetative cells from spores and dead cells could help to further the understanding of CDI.

DOI： 10.1111/1348-0421.12189

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Mycotic Abdominal Aortic Aneurysm Caused by Campylobacter fetus: A Case Report and Literature Review Reviewed International journal

Hideharu Hagiya, Mitsuaki Matsumoto, Hiroshi Furukawa, Tomoko Murase, Fumio Otsuka

ANNALS OF VASCULAR SURGERY   28 ( 8 )   1933.e7 - 1933.e14   2014.11

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Campylobacter spp. usually cause gastrointestinal infections, but among them, Campylobacter fetus is a well-known organism causing mycotic abdominal aortic aneurysm (MAAA), which requires proper surgical intervention and antibiotic therapy. We report a 65-year-old man who was successfully treated by an in situ operation using a rifampicin (RFP) ebonded J-Graft for C. fetus-induced MAAA. We performed a review of the English literature on MAAA caused by C. fetus and summarized the results of the cases (28 cases). All but 2 of the patients (92.9%) were men. Blood culture and arterial wall culture were positive in 63% and 73.1% of the cases, respectively. Aneurysm rupture was seen in half of the patients, and approximately half of those patients died. Among the 18 patients who underwent in situ graft replacement, only 1 patient (5.6%) died after surgery. Antibiotic therapy was performed for more than 1 month in most cases, and overall mortality rate was 25.9% (7 of 27 cases, 3 deaths before the operation and 4 deaths after surgery). Although extra-anatomic bypass has been conventionally performed after complete resection of an MAAA, the utility of in situ surgery has generally been recognized. Our review suggests that the in situ operation can be a choice also in cases of C. fetus-associated MAAA. Furthermore, our case suggested the clinical utility of a newly manufactured prosthetic graft, J-Graft, for such surgical treatment.

DOI： 10.1016/j.avsg.2014.06.072

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Pantoea dispersa bacteremia caused by central line-associated bloodstream infection Reviewed

Hideharu Hagiya, Fumio Otsuka

BRAZILIAN JOURNAL OF INFECTIOUS DISEASES   18 ( 6 )   696 - 697   2014.11

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DOI： 10.1016/j.bjid.2014.06.0061413

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Emergence of third-generation cephalosporin-resistant Enterobacteriacae in a Japanese critical care setting. Reviewed International journal

Hagiya H, Murase T, Suzuki M, Otsuka F, Shibayama K

Acute medicine & surgery   1 ( 4 )   256 - 258   2014.10

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Aim: Extended-spectrum beta-lactamases and AmpC beta-lactamases give resistance to Enterobacteriaceae against cephalosporins, which are important drugs in various clinical settings. Within 5 days, a total of eight strains of Citrobacter freundii and two strains of Escherichia coli, all of which were resistant to third-generation cephalosporins, were isolated from six different patients in a critical care center. We carried out epidemiological and genetic studies to confirm the situation to be an outbreak by a single strain or a beta-lactamase-producing gene. Methods: A review of patients' clinical data, pulsed-field gel electrophoresis epidemiological study against the strains, and polymerase chain reaction analysis for the detection of extended-spectrum beta-lactamase genes (TEM, SHV, CTX-M-1, CTX-M-2, and CTX-M-9) and multiplex polymerase chain reaction analysis for plasmid-mediated AmpC-beta-lactamase genes were carried out. Results: Pulsed-field gel electrophoresis showed none of the subjects were genetically identical organisms. However, all strains possessed either extended-spectrum beta-lactamases (TEM, CTX-M-2, and CTX-M-9) or AmpC-beta-lactamases. One patient carried both extended-spectrum beta-lactamase- and AmpC- beta-lactamase-producing organisms. Conclusion: This study revealed that various types of easily transmittable drug resistance genes exist in the critical care setting concurrently. This case was not an outbreak of such strains, but the present situation might indicate a more serious condition than a mere outbreak of a single resistant strain. Enterobacteriaceae that possess extended-spectrum beta-lactamases or AmpC-beta-lactamases are increasingly common in many medical institutions in Japan, and constitutive monitoring of drug-resistant organisms and proper contact precautions are essential to prevent possible outbreaks.

DOI： 10.1002/ams2.64

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Clinical utility of string test as a screening method for hypermucoviscosity-phenotype Klebsiella pneumoniae. Reviewed International journal

Hagiya H, Watanabe N, Maki M, Murase T, Otsuka F

Acute medicine & surgery   1 ( 4 )   245 - 246   2014.10

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DOI： 10.1002/ams2.40

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Clinical characteristics of Raoultella ornithinolytica bacteremia: A case series and literature review Reviewed International journal

Yuto Haruki, Hideharu Hagiya, Akiko Sakuma, Tomoko Murase, Tetsuhiro Sugiyama, Sachiyo Kondo

JOURNAL OF INFECTION AND CHEMOTHERAPY   20 ( 9-10 )   589 - 591   2014.9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

Raoultella ornithinolytica is a rare pathogen in human infection and bacteremic cases had been scarcely reported. For further comprehension of the rare infection, we summarized clinical characteristics of 6 cases that were detected at our medical facility and 5 cases from previous literature. The most common infectious focus was biliary infection and elderly patients with a history of any biliary intervention or malignancy were considered to be at a great risk for the infection. The prognosis of the patients was quite satisfactory. Bacterial identification in this report was performed on the basis of biochemical tests alone, and further investigations by molecular analysis are required to confirm our findings. (C) 2014, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2014.05.005

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A Case of Vascular Graft Infection Caused by Staphylococcus lugdunensis after Femoropopliteal Bypass Operation Reviewed

Hideharu Hagiya, Mitsuaki Matsumoto, Takahiko Yamasawa, Yuto Haruki, Fumio Otsuka

ACTA MEDICA OKAYAMA   68 ( 3 )   171 - 175   2014.6

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

A 79-year-old man who had undergone a right femoropopliteal (FP) bypass operation 6 weeks previously was diagnosed with vascular graft infection caused by Staphylococcus lugdunensis. Another FP bypass operation was performed, with long-term administration of antibiotics, and the patient eventually recovered well without any recurrences for over 2 years. Although S. lugdunens is classified as coagulase-negative Staphylococcus, its pathogenicity has been reported to be equal to that of S. aureus. Based on the literature review, the organism characteristically colonizes the inguinal area of human skin; thus, operations such as FP bypass grafting may place patients at a relatively high risk for infection by S. lugdunensis, a potentially high-pathogenicity organism.

DOI： 10.18926/AMO/52658

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難治性MRSA感染症に対して高用量ダプトマイシンとリファンピシンの併用療法が有効であった一例

萩谷 英大, 寺坂 友博, 木村 耕介, 佐藤 明香, 浅野 喜久子, 早稲田 公一, 花山 宜久, 近藤 英生, 大塚 文男

日本病院総合診療医学会雑誌   6 ( 2 )   105 - 105   2014.6

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Effects of Antibiotics Administration on the Incidence of Wound Infection in Percutaneous Dilatational Tracheostomy Reviewed

Hideharu Hagiya, Hiromichi Naito, Shingo Hagioka, Shuji Okahara, Naoki Morimoto, Nobuchika Kusano, Fumio Otsuka

ACTA MEDICA OKAYAMA   68 ( 2 )   57 - 62   2014.4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OKAYAMA UNIV MED SCHOOL  

The effect of antibiotics during the perioperative period of percutaneous dilatational tracheostomy (PDT) is still controversial. A total of 297 patients who underwent the PDT procedure were divided into 2 groups: those administered antibiotics perioperatively and those not administered antibiotics. Wound infections were noted in 7 cases (incidence rate, 2.36%) and no death was recorded. Of the 69 patients without antibiotics, 5 developed wound infections (incidence rate, 7.25%), while only 2 of the 228 patients with antibiotics developed wound infections (incidence rate, 0.88%) (p = 0.002; risk ratio, 8.82; 95% confidence interval, 1.67-46.6). Of the 7 cases of wound infection, 5 cases occurred during the early period after PDT (within 7 days). Collectively, the present results suggest that prophylactic administration of antibiotics may prevent the incidence of PDT-induced wound infection, especially in the early phase after the PDT procedures. The need for antibiotics in PDT should be reconsidered.

DOI： 10.18926/AMO/52402

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Chromobacterium violaceum nosocomial pneumonia in two Japanese patients at an intensive care unit Reviewed International journal

Hideharu Hagiya, Tomoko Murase, Masato Suzuki, Keigo Shibayama, Yumi Kokumai, Naoto Watanabe, Miyako Maki, Fumio Otsuka

JOURNAL OF INFECTION AND CHEMOTHERAPY   20 ( 1-2 )   139 - 142   2014.1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

Chromobacterium violaceum is sensitive to temperature and the infection is usually confined to tropical or subtropical regions. Since Japan has a warm climate, C. violaceum has been scarcely isolated from clinical specimens. With global warming, however, the geographical distribution of C violaceum infection is likely to change. We report two cases of C violaceum nosocomial pneumonia that occurred at an intensive care center in Japan. C violaceum was first detected from a patient in the same center as a pathogenic organism of pneumonia. Later, the organism was isolated from sputum and a ventilator circuit tube of another patient in the center. The two patients were admitted to the center in nearby beds for several days. All of the pathogens were confirmed to be C violaceum by the nucleic acid sequence of the 16S rRNA gene and were proven to be genetically identical organisms by pulsed field gel electrophoresis. Both patients were managed with well-humidified and heated oxygen using a venturi mask and ventilator to promote excretion of sputum. It was thought that the medical respiratory care devices that provide a humid and warm environment, an optimal condition for proliferation of C violaceum, can contribute to C violaceum infection in a hospital environment. (C) 2013, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jiac.2013.10.001

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Postpartum Breast Abscess Caused by Community-Acquired Methicillin-Resistant Staphylococcus aureus in Japan Reviewed

Hideharu Hagiya, Sumiko Shiota, Wakana Sugiyama, Fumio Otsuka

BREASTFEEDING MEDICINE   9 ( 1 )   45 - 46   2014.1

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Language：English   Publisher：MARY ANN LIEBERT, INC  

DOI： 10.1089/bfm.2013.0057

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Triangle Sign on Neck MRI Reviewed

Kosuke Kimura, Hideharu Hagiya, Yoshihisa Hanayama, Fumio Otsuka

INTERNAL MEDICINE   53 ( 9 )   1035 - 1036   2014

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DOI： 10.2169/internalmedicine.53.1777

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Successful Treatment of Persistent MRSA Bacteremia using High-dose Daptomycin Combined with Rifampicin Reviewed

Hideharu Hagiya, Tomohiro Terasaka, Kosuke Kimura, Asuka Satou, Kikuko Asano, Koichi Waseda, Yoshihisa Hanayama, Fumio Otsuka

INTERNAL MEDICINE   53 ( 18 )   2159 - 2163   2014

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

We herein report a case of persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia that was successfully treated with combination therapy consisting of high-dose daptomycin (DAP, 10 mg/kg) and rifampicin. The patient's condition was complicated with multiple infectious foci, including an iliopsoas abscess and epidural abscess, as well as discitis and spondylitis at the cervical, thoracic and lumbar levels. Monotherapy treatments with vancomycin, linezolid and usual-dose DAP were all ineffective. It has been shown that usual-dose DAP administration may result in the emergence of a resistant strain and treatment failure. We would like to emphasize the importance of high-dose DAP therapy for MRSA bacteremia, a condition with a potentially high mortality rate.

DOI： 10.2169/internalmedicine.53.2711

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Ceftriaxone-induced Biliary Sludge in a Patient with Uncontrolled Diabetes Reviewed

Hideharu Hagiya, Kou Hasegawa, Kikuko Asano, Fumio Otsuka

INTERNAL MEDICINE   53 ( 21 )   2549 - 2550   2014

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DOI： 10.2169/internalmedicine.53.3377

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Fosfomycin for the Treatment of Prostate Infection Reviewed

Hideharu Hagiya, Megumi Ninagawa, Kou Hasegawa, Tomohiro Terasaka, Kosuke Kimura, Koichi Waseda, Yoshihisa Hanayama, Toshiaki Sendo, Fumio Otsuka

INTERNAL MEDICINE   53 ( 22 )   2643 - 2646   2014

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

A 69-year-old man with diabetes mellitus was diagnosed with a prostate abscess. Although the pathogen was fluoroquinolone-resistant Escherichia coli and the oral administration of trimethoprim-sulfamethoxazole was initiated, the infection recurred after three months. The antibiotic therapy was subsequently changed to intravenous fosfomycin, and the patient's condition promptly improved. Four weeks of fosfomycin therapy was successfully continued without any adverse events. In the era of antibiotic resistance, revival of forgotten drugs is an important issue for clinicians. Fosfomycin can be applied as an alternative option for prostate infections, considering the remaining susceptibility of multidrug-resistant pathogens to fosfomycin and the good pharmacokinetics of this drug in prostatic tissue.

DOI： 10.2169/internalmedicine.53.3098

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Recurrent Stenotrophomonas maltophilia Bacteremia after Iliac Crest Bone Graft Harvest Reviewed

Hideharu Hagiya, Hiroko Ogawa, Tomoharu Ishida, Tomohiro Terasaka, Kosuke Kimura, Koichi Waseda, Yoshihisa Hanayama, Masahiro Horita, Yasunori Shimamura, Eisei Kondo, Fumio Otsuka

INTERNAL MEDICINE   53 ( 15 )   1693 - 1698   2014

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

We describe a rare case of recurrent Stenotrophomonas maltophilia bacteremia in a previously healthy 45-year-old man. The infection was caused by osteomyelitis at the site of an iliac crest bone graft harvest. A genetic analysis using enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) revealed that the blood isolates and pathogens obtained from the surgical wound were identical. Initial treatment with levofloxacin and cefozopran was ineffective, but the patient's infection was successfully treated by long-term administration of latamoxef and trimethoprim-sulfamethoxazole. The present case suggests that attention should be given to the possibility of S. maltophilia infection in any situations.

DOI： 10.2169/internalmedicine.53.1995

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Epiglottic Aphthous Ulcers Reviewed

Hideharu Hagiya, Hiroyuki Hanakawa, Takayuki Katsuyama, Fumio Otsuka

INTERNAL MEDICINE   53 ( 15 )   1731 - 1731   2014

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DOI： 10.2169/internalmedicine.53.2734

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Filarial Chyluria as a Rare Cause of Urinary Retention Reviewed

Hideharu Hagiya, Tomohiro Terasaka, Kosuke Kimura, Asuka Satou, Kikuko Asano, Koichi Waseda, Yoshihisa Hanayama, Takahide Takahashi, Michinori Aoe, Koji Iio, Toshiyuki Watanabe, Eisei Kondo, Fumio Otsuka

INTERNAL MEDICINE   53 ( 17 )   2001 - 2005   2014

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We herein describe a case of Wuchereria bancrofti infection in a previously healthy 37-year-old Nepalese man. The patient presented with a history of milky urine with subsequent acute urinary retention lasting for a few days. The presence of microfilariae was confirmed on both peripheral blood and urine smears obtained at midnight. He was conservatively treated with diethylcarbamazine combined with doxycycline. Filariasis was previously endemic in southern parts of Japan, although it has been eradicated. Clinicians should remember filariasis as a potential etiology of urinary retention, especially in cases that may be associated with imported infectious disease.

DOI： 10.2169/internalmedicine.53.2572

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Calcium Oxalate Crystals in the Lungs Reviewed

Hideharu Hagiya, Soichiro Fushimi, Junya Itakura, Fumio Otsuka

INTERNAL MEDICINE   53 ( 17 )   2025 - 2026   2014

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DOI： 10.2169/internalmedicine.53.2772

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Actinomyces meyeri Meningitis: The Need for Anaerobic Cerebrospinal Fluid Cultures Reviewed

Hideharu Hagiya, Fumio Otsuka

INTERNAL MEDICINE   53 ( 1 )   67 - 71   2014

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We herein present a rare case of Actinomyces meyeri-induced meningitis that occurred in a patient of advanced age with poor oral hygiene. Although Gram staining of the cerebrospinal fluid (CSF) revealed Grampositive rods and a blood culture was positive for the organism, a bacterial culture of the CSF was negative. Anaerobic cultures of CSF specimens are not routinely performed; however, anaerobes are sometimes involved in central nervous system infection. We therefore believe that anaerobic cultures should be considered in high-risk cases, such as those involving necrotizing bowel lesions or poor oral hygiene. A negative result on a CSF culture can result in misdiagnosis and inappropriate treatment.

DOI： 10.2169/internalmedicine.53.0403

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Acute Generalized Exanthematous Pustulosis Caused by Daptomycin in a Critically Ill Burn Victim Reviewed

Hideharu Hagiya, Maya Kimura, Toru Miyamoto, Yuto Haruki, Fumio Otsuka

INTERNAL MEDICINE   53 ( 5 )   511 - 514   2014

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Acute generalized exanthematous pustulosis (AGEP) is a self-limiting type of drug eruption that frequently occurs as a reaction to antibiotics, particularly penicillins or macrolides. Daptomycin (DAP) is a newly developed antibiotic that specifically targets methicillin-resistant Staphylococcus aureus infection. We herein present the case of a 77-year-old severe burn victim who was diagnosed with DAP-induced AGEP while receiving treatment in an intensive care unit. Although rare, physicians should be aware that the administration of DAP can cause AGEP, which may complicate the clinical course of patients with a high fever and inflammation.

DOI： 10.2169/internalmedicine.53.0679

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Rhombencephalitis Caused by Listeria monocytogenes Reviewed

Hideharu Hagiya, Fumio Otsuka

INTERNAL MEDICINE   53 ( 6 )   639 - 640   2014

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DOI： 10.2169/internalmedicine.53.1346

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Comprehensive Analysis of Systemically Disseminated ST8/non-USA300 type Community-acquired Methicillin-resistant Staphylococcus aureus Infection Reviewed

Hideharu Hagiya, Junzo Hisatsune, Taro Kojima, Sumiko Shiota, Hiromichi Naito, Shingo Hagioka, Naoki Morimoto, Fumio Otsuka, Motoyuki Sugai

INTERNAL MEDICINE   53 ( 8 )   907 - 912   2014

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Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is genetically heterogeneous and various genotypes are spreading worldwide. We herein report a case of systematically disseminated Japan-intrinsic CA-MRSA infection that was successfully treated. A genetically identical single strain was isolated from a total of 11 different parts of the patient's body, and the pathogen was found to be multilocus sequence type 8, staphylococcal cassette chromosome mec IV, coagulase type III and negative for both Panton-Valentine leukocidin and arginine catabolic mobile element. The epidemiology and pathogenicity of the Japan-intrinsic CA-MRSA strain remain unknown, and further investigation of this life-threatening organism is warranted.

DOI： 10.2169/internalmedicine.53.1746

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Lower Limb Infection in an Infant with Haemophilus influenzae Serotype b

Hideharu Hagiya, Fumio Otsuka

General Medicine   15 ( 1 )   56 - 58   2014

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DOI： 10.14442/general.15.56

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[Aortic valve-sparing operation for chronic dissecting aneurysm of the sinus of valsalva associated with redissection in a young woman who experienced out-of-hospital cardiac arrest]. Reviewed

Matsumoto M, Kubo Y, Kemmochi R, Yamasawa T, Oka T, Iwasaki J, Morimoto N, Hagioka S, Sugiyama J, Hagiya H

Kyobu geka. The Japanese journal of thoracic surgery   66 ( 9 )   799 - 802   2013.8

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A 38-year-old woman was admitted to our hospital because she experienced cardiopulmonary arrest at her wedding;her cardiac beats were resumed 20 min after cardiopulmonary resuscitation performed by her relatives and hotel staffs. Enhanced computed tomography revealed acute aortic redissection in chronic dissecting aneurysm in the right sinus of Valsalva, which was believed to have occurred in the 4th month of pregnancy 2 years before. Echocardiography showed moderate aortic regurgitation. We performed aortic valve-sparing operation and ascending aortic replacement with partial remodeling of the right sinus of Valsalva. She returned to work 2 months later without high-order dysfunction.

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[Surgical treatment of traumatic aortic rupture]. Reviewed

Yamasawa T, Matsumoto M, Kubo Y, Kemmochi R, Morimoto N, Hagioka S, Sugiyama J, Hagiya H, Nakai M

Kyobu geka. The Japanese journal of thoracic surgery   66 ( 7 )   537 - 540   2013.7

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This report focuses on 3 cases of traumatic aortic dissection or rupture at the isthmus. We selected 3 different methods of treatment. In the 1st case, we performed an emergency operation with graft replacement of the proximal descending aorta. In the 2nd case, we performed elective graft replacement 5 months after the rupture under careful blood pressure control. Thirdly, we performed emergency stent grafting at the isthmus, the rupture site. All cases were successfully treated, but it remains difficult to select the method of treatment for multisystem disorder. Our current strategy for traumatic rupture at the isthmus is immediate stent grafting. It will also be a very useful procedure for multisystem trauma.

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Systemic varicella-zoster virus infection in two critically ill patients in an intensive care unit Reviewed International journal

Hideharu Hagiya, Maya Kimura, Toru Miyamoto, Fumio Otsuka

VIROLOGY JOURNAL   10   225 - 225   2013.7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Varicella-zoster virus (VZV) usually causes localized zoster in adults. However, in immunocompromised patients, it can cause systemic infection accompanied by complications such as pneumonia, encephalitis, and hepatitis. Although most of critically ill patients in intensive care unit (ICU) are immunologically compromised, they are usually not considered to be at risk for systemic VZV infection.
We report two cases of systemic VZV infection occurring in critically ill patients in an ICU. One patient was a 69-year-old man with Streptococcus pneumoniae-induced purpurafulminans, and the other was a 75-year-old woman with severe acute pancreatitis. During the clinical course in the ICU, characteristic vesicles with umbilical fossa appeared diffusely and bilaterally on their face, trunk, and extremities. VZV-specific IgG levels were confirmed to be elevated compared to that of the pre-onset, and a diagnosis of recurrent VZV infection was made in both patients. The patients were treated at the same ICU but did not coincide with each other; therefore a cross-infection was unlikely. They were treated with intravenous acyclovir, but the latter patient eventually died of respiratory failure.
VZV infection can cause a number of serious complications, and can lead to death in some patients. Early detection and proper treatment are needed to prevent the infection from spreading out and save the patients. It might be necessary to consider antiviral prophylaxis against VZV infection for a part of critically ill patients in ICU, although the effectiveness of this approach is yet to be established.

DOI： 10.1186/1743-422X-10-225

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Clinical Characteristics of Ochrobactrum anthropi Bacteremia Reviewed International journal

Hideharu Hagiya, Kouhei Ohnishi, Miyako Maki, Naoto Watanabe, Tomoko Murase

JOURNAL OF CLINICAL MICROBIOLOGY   51 ( 4 )   1330 - 1333   2013.4

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The clinical picture of Ochrobactrum anthropi infection is not well described because the infection is rare in humans and identification of the pathogen is difficult. We present a case of O. anthropi bacteremia that was initially misidentified as Ralstonia paucula and later identified by 16S rRNA sequencing and recA analysis.

DOI： 10.1128/JCM.03238-12

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Co-infection with invasive pulmonary aspergillosis and Pneumocystis jirovecii pneumonia after corticosteroid therapy Reviewed International journal

Hideharu Hagiya, Takayoshi Miyake, Yusuke Kokumai, Tomoko Murase, Yasutoshi Kuroe, Hiroyoshi Nojima, Junichi Sugiyama, Hiromichi Naito, Shingo Hagioka, Naoki Morimoto

JOURNAL OF INFECTION AND CHEMOTHERAPY   19 ( 2 )   342 - 347   2013.4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

A 95-year-old man with chronic obstructive pulmonary disease and chronic hepatitis C virus infection was treated for acute lung injury caused by Chlamydophila pneumoniae with antibiotics and high-dose corticosteroids. In total, 7,500 mg methylprednisolone and 680 mg prednisolone were administered over 21 days. However, respiratory failure progressed, and chest computed tomography (CT) scan showed bilateral ground-glass opacity and cavity-forming consolidation in the right upper lobe. Despite intensive therapy, the patient died of multiple organ failure on day 7. CT-guided necropsy was performed, and pathological examination revealed invasive pulmonary aspergillosis and Pneumocystis jirovecii pneumonia. Invasive pulmonary aspergillosis and P. jirovecii pneumonia are both life-threatening opportunistic fungal infections. Co-infection of these organisms is rare but possible if the patient is in an extremely immunocompromised state. Short-term but high-dose systemic corticosteroid therapy was considered to be the risk factor in this case. We should pay more attention to immunocompromised hosts who might be suffering from co-infection of opportunistic infections. Moreover, we need to consider preventive measures in such high-risk cases.

DOI： 10.1007/s10156-012-0473-9

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Delftia acidovorans bacteremia caused by bacterial translocation after organophosphorus poisoning in an immunocompetent adult patient Reviewed International journal

Hideharu Hagiya, Tomoko Murase, Junichi Sugiyama, Yasutoshi Kuroe, Hiroyoshi Nojima, Hiromichi Naito, Shingo Hagioka, Naoki Morimoto

JOURNAL OF INFECTION AND CHEMOTHERAPY   19 ( 2 )   338 - 341   2013.4

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A 46-year-old woman was transferred to our emergency unit because of impaired consciousness and respiratory failure with the history of excessive pesticide intake. The patient was hypersalivative and had bilateral pupillary miosis. Laboratory results showed markedly decreased cholinesterase. She was intubated and treated in the intensive care unit with the diagnosis of organophosphorus poisoning. The patient had persisted diarrhea, with a high fever and stomach tenderness on day 10. Whole-body contrast enhanced computed tomography revealed a swollen, enhanced small intestinal wall, and blood culture identified Delftia acidovorans. She was diagnosed as D. acidovorans bacteremia, probably caused by bacterial translocation based on the clinical presentation and the exclusion of other sources, and treated well with a total of 8 days of antibiotic therapy. So far as we know, this is the first case of D. acidovorans bacteremia that was presumably caused by bacterial translocation after organophosphorus poisoning in an immunocompetent adult patient.

DOI： 10.1007/s10156-012-0472-x

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Disseminated Gonococcal Infection in An Elderly Japanese Man Reviewed

Hideharu Hagiya, Nobuhiko Onishi, Hirotaka Ebara, Yoshihisa Hanayama, Susumu Kokeguchi, Motoko Nose, Nobuchika Kusano, Fumio Otsuka

INTERNAL MEDICINE   52 ( 23 )   2669 - 2673   2013

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We herein present the case of a 69-year-old Japanese man who had unprotected sexual contact with a local commercial sex worker in an East Asian country and was diagnosed as having disseminated gonococcal infection (DGI). The organism was confirmed to be Neisseria gonorrhoeae based on 16S rRNA sequencing and positive results for the cppB gene. This case indicates that a diagnosis of DGI should also be considered in elderly individuals. DGI potentially causes many complications, and the pathogen has recently been reported to be resistant to various antibiotics. Physicians must therefore pay more attention to the possible occurrence of DGI in various clinical settings.

DOI： 10.2169/internalmedicine.52.1033

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Is wet swab superior to dry swab as an intranasal screening test? Reviewed International journal

Hideharu Hagiya, Mitsunobu Mio, Tomoko Murase, Keiko Egawa, Yumi Kokumai, Taeko Uchida, Naoki Morimoto, Fumio Otsuka, Sumiko Shiota

Journal of Intensive Care   1 ( 1 )   10 - 10   2013

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BioMed Central Ltd.  

Methicillin-resistant Staphylococcus aureus is still a great concern, and recognition of the carrier is essential for appropriate infection control in intensive care units. The utility of wet swab compared to dry swab as an intranasal screening test has not been well assessed yet. A comparative study of the wet and dry swab in its ability to detect the organism was performed against critically ill patients, and it was found that there were no statistically significant differences between the two different methods. The wet swab did not show increased sensitivity compared to dry one.

DOI： 10.1186/2052-0492-1-10

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Emphysematous liver abscesses complicated by septic pulmonary emboli in patients with diabetes: Two cases Reviewed

Hideharu Hagiya, Yasutoshi Kuroe, Hiroyoshi Nojima, Shinkichi Otani, Junichi Sugiyama, Hiromichi Naito, Susumu Kawanishi, Shingo Hagioka, Naoki Morimoto

Internal Medicine   52 ( 1 )   141 - 145   2013

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An emphysematous liver abscess is a fatal condition that often occurs in patients with uncontrolled diabetes mellitus. I herein describe two cases of Klebsiella pneumoniae-induced emphysematous liver abscesses complicated by septic pulmonary emboli in patients with poorly controlled diabetes mellitus. Both patients showed hemoglobin A1c levels of more than 10% and did not present with any abdominal symptoms on admission. However, they were diagnosed and successfully treated with percutaneous transhepatic abscess drainage and antibiotics. This fatal disease should be taken into consideration in patients with uncontrolled diabetes mellitus who suffer from prolonged fevers and uncharacteristic general malaise. © 2013 The Japanese Society of Internal Medicine.

DOI： 10.2169/internalmedicine.52.8737

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Group A streptococcal meningitis in a patient with palmoplantar pustulosis Reviewed

Hideharu Hagiya, Fumio Otsuka

Internal Medicine   52 ( 23 )   2675 - 2678   2013

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A 64-year-old man with a 10-year history of palmoplantar pustulosis, a recent history of cranial surgery and a persistent upper airway infection presented with a high fever and deep coma. The patient was diagnosed with Group A Streptococcal meningitis and promptly treated with antibiotics. Although his general condition recovered well, sensorineural hearing loss and facial palsy remained. Group A Streptococcal meningitis is a rare condition, and its typical clinical picture and epidemiological features remain poorly understood. Physicians need to be more aware of this infection, which is extremely rare but frequently causes various complications and yields a high mortality. © 2013 The Japanese Society of Internal Medicine.

DOI： 10.2169/internalmedicine.52.0499

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A Fatal Case of Streptococcal Toxic Shock Syndrome due to Streptococcus dysgalactiae subsp equisimilis Possibly Caused by an Intramuscular Injection Reviewed

Hideharu Hagiya, Shunji Okita, Yasutoshi Kuroe, Hiroyoshi Nojima, Shinkichi Otani, Junichi Sugiyama, Hiromichi Naito, Susumu Kawanishi, Shingo Hagioka, Naoki Morimoto

INTERNAL MEDICINE   52 ( 3 )   397 - 402   2013

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An 88-year-old man died of streptococcal toxic shock syndrome due to a group G streptococcus infection that was possibly caused by an intramuscular injection given 30 hours earlier in his right deltoid muscle. The causative pathogen was later identified to be Streptococcus dysgalactiae subsp. equisimilis (stG485). Although providing intramuscular injections is an essential skill of health care workers that is performed daily worldwide, it may constitute a port of entry for pathogens via skin breaches that can cause life-threatening infections. All invasive procedures should be carefully performed, especially when immunologically compromised patients are involved.

DOI： 10.2169/internalmedicine.52.8846

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Pyometra Perforation Caused by Actinomyces without Intrauterine Device Involvement. Reviewed International journal

Hagiya H

Case reports in obstetrics and gynecology   2013   658902 - 658902   2013

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An 86-year-old woman with diabetes mellitus and severe decubitus at the sacral and calcaneal regions stemming from poor daily activity was diagnosed with pyometra perforation caused by Actinomyces. No foreign materials, including an IUD, were found inside the uterus. Pyometra is usually caused by Enterobacteriaceae or anaerobes derived from the gastrointestinal tract. The virulence of Actinomyces is rather low, and, in almost all the reported cases of Actinomyces-related pyometra, an intrauterine device (IUD) was involved. Although rare, Actinomyces may be ascribed as a virulent pathogen that causes pyometra in the absence of foreign materials.

DOI： 10.1155/2013/658902

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Successful Treatment of Recurrent Candidemia due to Candidal Thrombophlebitis Associated with a Central Venous Catheter Using a Combination of Fosfluconazole and Micafungin Reviewed

Hideharu Hagiya, Hiroki Kajioka

INTERNAL MEDICINE   52 ( 18 )   2139 - 2143   2013

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We herein report the case of an 85-year-old woman presenting with right internal jugular vein candidal thrombophlebitis associated with central venous catheters (CTCVC). The infecting agent was Candida albicans, which caused recurrent candidemia five times in total. Micafungin (MCFG) alone was ineffective; however, the combination of MCFG with fosfluconazole (F-FLCZ) successfully treated the patient without a need for any anticoagulant or surgical therapies. To the extent of our knowledge, this is the first report of CTCVC being successfully treated with a combination of F-FLCZ and MCFG. These new antifungal agents have better efficacy, tolerability and bioavailability; therefore, they can be useful alternatives to classical combination therapies such as amphotericin-B and 5-fluorocytosine.

DOI： 10.2169/internalmedicine.52.0584

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Ineffectiveness of Daptomycin in the Treatment of Septic Pulmonary Emboli and Persistent Bacteremia Caused by Methicillin-resistant Staphylococcus aureus Reviewed

Hideharu Hagiya, Shingo Hagioka, Fumio Otsuka

INTERNAL MEDICINE   52 ( 22 )   2577 - 2582   2013

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A 73-year-old man with long-term food deprivation and total parenteral nutrition was diagnosed with septic pulmonary emboli (SPE) and a persistent bacteremia caused by central line-associated blood stream methicillin-resistant Staphylococcus aureus (MRSA) infection. Although daptomycin (DAP) failed to treat the persistent bacteremia, linezolid successfully controlled it. DAP is inactivated by lung surfactant, and therefore, it should not be administered for lower respiratory infections. However, SPE caused by MRSA has been reported to be treatable with DAP since it is an infection of the lung parenchyma. We herein report the lack of effect of daptomycin in SPE treatment.

DOI： 10.2169/internalmedicine.52.0023

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Necrotizing Duodenitis Caused by Clostridium perfringens Type A in a Japanese Young Man Reviewed

Hideharu Hagiya, Hiromichi Naito, Junichi Sugiyama, Hiroyoshi Nojima, Shingo Hagioka, Naoki Morimoto

INTERNAL MEDICINE   51 ( 20 )   2973 - 2976   2012

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JAPAN SOC INTERNAL MEDICINE  

A 21-year-old Japanese man with a history of marked body weight loss over a short period of time died of necrotizing duodenitis caused by Clostridium perfringens (C. perfringens) type A. C. perfringens type A is considered to usually cause self-limiting gastroenteritis. Necrotizing enteritis sometimes occurs due to C. perfringens in developing countries; however, it is primarily caused by the type C strain and its site of onset is typically the jejunum or ileum. This is a rare case of necrotizing duodenitis caused by C. perfringens type A in a Japanese young man. Physicians need to be more aware of this emerging fatal disease in developed countries.

DOI： 10.2169/internalmedicine.51.8407

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Severe Soft Tissue Infection of the Lower Extremity Caused by Haemophilus influenzae (serotype f, biotype II) in an Adult Patient Reviewed

Hideharu Hagiya, Tomoko Murase, Hiromichi Naito, Shingo Hagioka, Naoki Morimoto

INTERNAL MEDICINE   51 ( 13 )   1783 - 1787   2012

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The infection caused by non-b-type Haemophilus influenzae has been increasing in this Hib (H. influenzae serotype b) vaccination era. H. influenzae serotype f (Hif) is considered as one of those emerging pathogens. In general, H. influenzae is a common pathogen of such as pneumonia, otitis media, and meningitis, but is rare in soft tissue infection, especially at the extremity. We report a rare case of severe soft tissue infection caused by Hif which occurred at the lower extremity of immunocompetent adult patient.

DOI： 10.2169/internalmedicine.51.7209

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Successfully Conducted Vaccination Drive against Vaccine-Preventable Diseases for Staff at Our Facility Reviewed

Hideharu Hagiya, Yumi Kokumai

Japanese Journal of Environmental Infections   27 ( 6 )   405 - 411   2012

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Language：English   Publisher：Japanese Society for Infection Prevention and Control  

Preventing occupational infections is one of the most important activities of the infection control team. It is recommended that all healthcare workers be protected from vaccine-preventable diseases (VPDs) by administering vaccines. We conducted a vaccination drive at our facility because of disseminated varicella-zoster virus (VZV) infection in a patient in the intensive care unit and the upcoming operation of a patient with mumps. A total of 984 persons were evaluated for antibody titers of measles, rubella, mumps, and VZV, and individuals were vaccinated if the titers indicated the need for vaccination. It took approximately 7 months from the planning to the completion of the vaccination drive. Inoculation rates were as follows: measles, 81.9%
rubella, 76.9%
mumps, 76.2%
and VZV, 60%. Our vaccination drive was conducted successfully in a relatively short period of time and we achieved a high vaccination rate mainly due to the following 4 reasons: we recognized the need for vaccination intensely after we came across 2 cases of VPDs at our facility
the vaccination drive was carried out at the same time as the business improvement plan of the hospital was implemented
the hospital covered the entire antibody titer testing and half of the vaccination costs
simultaneous vaccination was allowed with different vaccines. © 2012, Japanese Society for Infection Prevention and Control. All rights reserved.

DOI： 10.4058/jsei.27.405

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