Faculty Profiles - OTSUKA Fumio

Papers - OTSUKA Fumio

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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 17 ( 6 ) 608 - 616 2021.11

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

新型コロナウイルス感染症対策の一環として,「新型コロナウイルス感染症対応従事者慰労金交付事業」が実施されたが,その影響・有効性に関するデータは乏しい。2021年4月26日〜5月31日に,岡山県・香川県・広島県の医療機関に勤務する職員を対象にウェブ・アンケートによる横断調査を実施した。1001名からの回答において,慰労金受給率は95.8%であり,59.5%は本事業に満足したと回答した。職種別満足度は,医師(60.8%),メディカルスタッフ(63.9%)に比べて看護職(46.3%)で低かった(p<0.001)。医療機関内職員のみならず,救急隊員,保健所職員,高齢者介護施設の職員も慰労金が支払われるべき業種として高率に理解を得た。慰労金交付事業は,医療従事者等の外的モチベーションとして概ね機能したと考えられるが,給付金額や対象者の選定に関しては検討の余地がある。(著者抄録)

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Subcutaneous edema as rare complication of abdominal paracentesis. International journal

Yuki Otsuka, Hirokazu Nagaoka, Yasuhiro Nakano, Hiroyuki Sakae, Kou Hasegawa, Fumio Otsuka

Clinical case reports 9 ( 11 ) e05116 2021.11

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

Although ascites leakage to the skin is the most frequent complication after abdominal paracentesis, leakage to the subcutaneous space has not been reported. Here, we report a subcutaneous effusion after paracentesis suggesting ascites leakage. We should be aware of this rare complication due to the potential risk of dissemination.

DOI： 10.1002/ccr3.5116

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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

Language：Japanese Publisher：(株)ライフメディコム

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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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

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

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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Temporal artery thickening in giant cell arteritis. International journal

Hiromi Ihoriya, Yasuhiro Nakano, Fumio Otsuka

BMJ case reports 14 ( 10 ) 2021.10

Radiologic features of Erdheim-Chester disease. International journal

Koichiro Yamamoto, Yasuhiro Nakano, Kou Hasegawa, Fumio Otsuka

Rheumatology (Oxford, England) 61 ( 7 ) e209 2021.10

Idiopathic combined adrenocorticotropin and growth hormone deficiency mimicking chronic fatigue syndrome. International journal

Kazuki Tokumasu, Kanako Ochi, Fumio Otsuka

BMJ case reports 14 ( 10 ) 2021.10

Language：English Publishing type：Research paper (scientific journal) Publisher：BMJ PUBLISHING GROUP

A 42-year-old man who had suffered from severe fatigue for 5 years was diagnosed as having chronic fatigue syndrome (CFS) and fibromyalgia. Endocrinological workup using combined anterior pituitary function tests showed that the patient had adrenocorticotropin hormone (ACTH) deficiency, with a normal pituitary MRI. Treatment with a physiologic dose of oral hydrocortisone replacement physically ameliorated his general fatigue. A secondary workup using a growth hormone-releasing peptide-2 test revealed that he also had growth hormone (GH) deficiency, and GH replacement therapy was started. His muscle pain and depression were improved by the therapy. Here, we present a rare case of combined deficiency of ACTH and GH in a middle-aged man with severe general fatigue. This case report aims to raise awareness of combined deficiency of ACTH and GH as a differential diagnosis of CFS and its mimics.

DOI： 10.1136/bcr-2021-244861

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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

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

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

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

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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Biphasic Roles of Clock Genes and Bone Morphogenetic Proteins in Gonadotropin Expression by Mouse Gonadotrope Cells. International journal

Yoshiaki Soejima, Nahoko Iwata, Yasuhiro Nakano, Koichiro Yamamoto, Atsuhito Suyama, Takahiro Nada, Fumio Otsuka

International journal of molecular sciences 22 ( 20 ) 2021.10

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

Roles of Clock genes and the bone morphogenetic protein (BMP) system in the regulation of gonadotropin secretion by gonadotropin-releasing hormone (GnRH) were investigated using mouse gonadotropin LβT2 cells. It was found that luteinizing hormone (LH)β mRNA expression level in LβT2 cells changed gradually over time, with LHβ expression being suppressed in the early phase up to 12 h and then elevated in the late phase 24 h after GnRH stimulation. In addition, the mRNA expression levels of Clock genes, including Bmal1, Clock, Per2, and Cry1, also showed temporal changes mimicking the pattern of LHβ expression in the presence and absence of GnRH. Notably, the expression levels of Bmal1 and Clock showed strong positive correlations with LHβ mRNA expression levels. Moreover, a functional link of the ERK signaling of mitogen-activated protein kinases (MAPKs) in the suppression of LHβ mRNA expression, as well as Bmal1 and Clock mRNA expression by GnRH at the early phase, was revealed. Inhibition of Bmal1 and Clock expression using siRNA was involved in the reduction in LHβ mRNA levels in the late phase 24 h after GnRH stimulation. Furthermore, in the presence of BMP-6 and -7, late-phase Bmal1 and LHβ mRNA expression after GnRH stimulation was significantly attenuated. Collectively, the results indicated that LH expression in gonadotrope cells exhibits Bmal1/Clock-dependent fluctuations under the influence of GnRH and that the fluctuations are regulated by ERK and BMPs in the early and late stages, respectively, in a phase-dependent manner after GnRH stimulation.

DOI： 10.3390/ijms222011186

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Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease. International journal

Yoshito Nishimura, David C Fajgenbaum, Sheila K Pierson, Noriko Iwaki, Asami Nishikori, Mitsuhiro Kawano, Naoya Nakamura, Koji Izutsu, Kengo Takeuchi, Midori Filiz Nishimura, Yoshinobu Maeda, Fumio Otsuka, Kazuyuki Yoshizaki, Eric Oksenhendler, Frits van Rhee, Yasuharu Sato

American journal of hematology 96 ( 10 ) 1241 - 1252 2021.10

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

Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly (TAFRO) syndrome is a heterogeneous entity manifesting with a constellation of symptoms described above that can occur in the context of idiopathic multicentric Castleman disease (iMCD) as well as infectious diseases, malignancies, and rheumatologic disorders. So, iMCD-TAFRO is an aggressive subtype of iMCD with TAFRO syndrome and often hyper-vascularized lymph nodes. Since we proposed diagnostic criteria of iMCD-TAFRO in 2016, we have accumulated new insights on the disorder and additional cases have been reported worldwide. In this systematic review and cohort analysis, we established and validated a definition for iMCD-TAFRO. First, we searched PubMed and Japan Medical Abstracts Society databases using the keyword "TAFRO" to extract cases. Patients with possible systemic autoimmune diseases and hematologic malignancies were excluded. Our search identified 54 cases from 50 articles. We classified cases into three categories: (1) iMCD-TAFRO (TAFRO syndrome with lymph node histopathology consistent with iMCD), (2) possible iMCD-TAFRO (TAFRO syndrome with no lymph node biopsy performed and no other co-morbidities), and (3) TAFRO without iMCD or other co-morbidities (TAFRO syndrome with lymph node histopathology not consistent with iMCD or other comorbidities). Based on the findings, we propose an international definition requiring four clinical criteria (thrombocytopenia, anasarca, fever/hyperinflammatory status, organomegaly), renal dysfunction or characteristic bone marrow findings, and lymph node features consistent with iMCD. The definition was validated with an external cohort (the ACCELERATE Natural History Registry). The present international definition will facilitate a more precise and comprehensive approach to the diagnosis of iMCD-TAFRO.

DOI： 10.1002/ajh.26292

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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

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

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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Celiac artery dissection in polycystic kidney disease. International journal

Koichiro Yamamoto, Kou Hasegawa, Kosuke Oka, Fumio Otsuka

Clinical case reports 9 ( 10 ) e04922 2021.10

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

Autosomal-dominant polycystic kidney disease (ADPKD) is rarely complicated by celiac artery dissection. Dissection of the aorta and its major branches should be carefully differentiated in ADPKD patients with acute-onset abdominal pain.

DOI： 10.1002/ccr3.4922

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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

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

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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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

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

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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Intravascular lymphoma presenting as spinal cord infarction. International journal

Yukichika Yamamoto, Yoshito Nishimura, Misa Okumura, Yuki Otsuka, Kosuke Oka, Kazuhiro Ikeuchi, Hisakazu Nishimori, Kohei Taniguchi, Fumio Otsuka

Postgraduate medical journal 97 ( 1152 ) 672 - 673 2021.10

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

Language：Japanese Publisher：(公社)日本医師会

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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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, Author Orcid Image, Yoshito Nishimura, Author Orcid Image, Torrey Czech, Author Orcid Image, Nobuhiko Kimura, Author Orcid Image, Hideharu Hagiya, Author Orcid Image, Toshihiro Koyama, Author Orcid Image, Fumio Otsuka, Author Orcid Image

2021.10

Triad signs shown by bone scintigraphy in FGF23-related osteomalacia. International journal

Koichiro Yamamoto, Hiroyuki Honda, Itsuro Ota, Fumio Otsuka

QJM : monthly journal of the Association of Physicians 2021.9

Sternoclavicular Joint Hypertrophy Involved in Polymyalgia Rheumatica.

Koichiro Yamamoto, Kosuke Oka, Kou Hasegawa, Fumio Otsuka

Internal medicine (Tokyo, Japan) 60 ( 18 ) 3057 - 3057 2021.9

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Papers - OTSUKA Fumio