Faculty Profiles - OTSUKA Fumio

Papers - OTSUKA Fumio

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Collection efficiency and safety of large-volume leukapheresis for the manufacturing of tisagenlecleucel. Reviewed International journal

Wataru Kitamura, Tomohiro Urata, Keiko Fujii, Takuya Fukumi, Kazuhiro Ikeuchi, Keisuke Seike, Hideaki Fujiwara, Noboru Asada, Daisuke Ennishi, Ken-Ichi Matsuoka, Fumio Otsuka, Yoshinobu Maeda, Nobuharu Fujii

Transfusion 2024.2

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

BACKGROUND: In patients with relapsed or refractory B cell acute lymphoblastic leukemia or B cell non-Hodgkin lymphoma (r/r B-ALL/B-NHL) with low CD3+ cells in the peripheral blood (PB), sufficient CD3+ cell yield in a single day may not be obtained with normal-volume leukapheresis (NVL). Large-volume leukapheresis (LVL) refers to the processing of more than three times the total blood volume (TBV) in a single session for PB apheresis; however, the efficiency and safety of LVL for manufacturing of tisagenlecleucel (tisa-cel) remain unclear. This study aimed to investigate the tolerability of LVL. STUDY DESIGN AND METHODS: We retrospectively collected data on LVL (≥3-fold TBV) and NVL (<3-fold TBV) performed for patients with r/r B-ALL/B-NHL in our institution during November 2019 and September 2023. All procedures were performed using a continuous mononuclear cell collection (cMNC) protocol with the Spectra Optia. RESULTS: Although pre-apheresis CD3+ cells in the PB were significantly lower in LVL procedures (900 vs. 348/μL, p < .01), all patients could obtain sufficient CD3+ cell yield in a single day with a comparably successful rate of final products (including out-of-specification) between the two groups (97.2% vs. 100.0%, p = 1.00). The incidence and severity of citrate toxicity (no patients with grade ≥ 3) during procedures was not significantly different between the two groups (22.2% vs. 26.1%, p = .43) and no patient discontinued leukapheresis due to any complications. CONCLUSION: LVL procedures using Spectra Optia cMNC protocol was well tolerated and did not affect the manufacturing of tisa-cel.

DOI： 10.1111/trf.17765

PubMed

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Penile cavernosal abscess after urethral injury Reviewed

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

Clinical Case Reports 12 ( 2 ) 2024.2

Authorship：Last author 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 ) 889 2024.2

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

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

PubMed

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【入院時から始める退院調整】診療情報提供書の書き方と注意点入院診療とかかりつけ医をつなぐために

大塚勇輝, 川口満理奈, 大塚文男

レジデントノート 25 ( 16 ) 2894 - 2902 2024.2

【新型コロナ後遺症-これまでの対応と問題点】

大塚勇輝, 徳増一樹, 植田圭吾, 大塚文男

日本医事新報 ( 5208 ) 18 - 27 2024.2

Language：Japanese Publisher：(株)日本医事新報社

[1]はじめに・いわゆる「新型コロナ後遺症」にいまだ多くの患者が苦しみ,わが国を含む世界的な社会問題となっている。[2]呼称と定義・「新型コロナ後遺症」などの用語の定義は,医学的には統一されていない。・NIHの「PASC」,WHOの「PCC」という用語には定義が定められ,2023年には診断基準案の提案もなされた。[3]コロナ・アフターケア外来とは・罹患後慢性期にかけての症状の遷延に対し,専門外来であるコロナ・アフターケア(CAC)外来を開設した。・1日1～2人の新規患者を受け入れ,800人以上の患者を対面診療してきた。[4]疫学・CAC外来へは,デルタ株流行時に感染者の約1.5%,オミクロン株では感染者の0.1%程度が受診となった。・CAC外来の受診患者は若干女性が多く,30～50歳代が60%,10歳代など若年者が14%だが,70歳代以上の受診は比較的少ない。・オミクロン株に感染したと思われる症例では,95%の患者で急性期は軽症であったが,後遺症は残っている。[5]症状・症状は多彩であるが,倦怠感・易疲労感が最多で,ブレインフォグは,特にオミクロン株で増加していた。[6]病態とメカニズム・感染後の炎症と免疫応答,自己免疫反応,血栓・血管内皮障害,腸内細菌叢変化,自律神経・内分泌障害,ウイルス残存など,種々の仮説がある。・抑うつ指数,FT4,倦怠感スケール,血中コルチゾール値の間に正の相関がみられる。・捲怠感や味覚・嗅覚障害を随伴する患者では,それぞれ成長ホルモン低値,FT4高値,コルチゾール低値の傾向がある。[7]治療とマネジメント・漢方薬の処方のほか,亜鉛補充,急性期の抗ウイルス薬やメトホルミンの処方にも,一定の効果が認められる。・総合診療的なアプローチで,全人的なケアを心がけている。[8]今後の課題・終診とできるまでに日数を要するほか,対応可能な医師・施設も不足している。(著者抄録)

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Mutual Effects of Orexin and Bone Morphogenetic Proteins on Catecholamine Regulation Using Adrenomedullary Cells. Reviewed International journal

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

International journal of molecular sciences 25 ( 3 ) 2024.1

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

Orexins are neuronal peptides that play a prominent role in sleep behavior and feeding behavior in the central nervous system, though their receptors also exist in peripheral organs, including the adrenal gland. In this study, the effects of orexins on catecholamine synthesis in the rat adrenomedullary cell line PC12 were investigated by focusing on their interaction with the adrenomedullary bone morphogenetic protein (BMP)-4. Orexin A treatment reduced the mRNA levels of key enzymes for catecholamine synthesis, including tyrosine hydroxylase (Th), 3,4-dihydroxyphenylalanie decarboxylase (Ddc) and dopamine β-hydroxylase (Dbh), in a concentration-dependent manner. On the other hand, treatment with BMP-4 suppressed the expression of Th and Ddc but enhanced that of Dbh with or without co-treatment with orexin A. Of note, orexin A augmented BMP-receptor signaling detected by the phosphorylation of Smad1/5/9 through the suppression of inhibitory Smad6/7 and the upregulation of BMP type-II receptor (BMPRII). Furthermore, treatment with BMP-4 upregulated the mRNA levels of OX1R in PC12 cells. Collectively, the results indicate that orexin and BMP-4 suppress adrenomedullary catecholamine synthesis by mutually upregulating the pathway of each other in adrenomedullary cells.

DOI： 10.3390/ijms25031585

PubMed

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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

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

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

PubMed

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特集 -"体験型"臨床クイズで習得する!-フィジカル診断エクセレンス -❺内分泌･代謝-10年以上続く原因不明の全身痛

髙瀬了輔, 片岡仁美, 大塚文男

総合診療 34 ( 1 ) 37 - 40 2024.1

Influence of the coronavirus disease 2019 pandemic on the post-graduate career paths of medical students: a cross-sectional study Reviewed

Ayumu Nishimura, Tomoko Miyoshi, Fumio Otsuka, Akihiro Matsukawa

BMC Medical Education 24 ( 1 ) 2024.1

Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Abstract

Background

The World Health Organization first declared the coronavirus disease 2019 (COVID-19) pandemic in March 2020 and announced the end of the emergency in May 2023. Additionally, the COVID-19 pandemic significantly impacted individuals globally, including medical students. Although the COVID-19 pandemic increased online education, it restricted clinical training, extracurricular activities, and interprovincial travel. Therefore, this study aimed to examine whether the COVID-19 pandemic influenced the choice of training hospitals and career paths among 3rd- to 6th-year medical students in Japan.

Methods

We developed a questionnaire comprising 21 multiple-choice and 1 open-ended questions, which was administered anonymously via online platforms. The survey targeted Japanese medical students to obtain insights into their preferences for training hospitals and career paths during the COVID-19 pandemic. Participants included 4th- to 6th-year medical students from 51 medical schools in Japan. The survey was conducted through student networks from 8 February 2022 to 20 March 2022.

Results

Overall, 507 medical students participated in the survey, with representation from various academic years as follows: 102 (20.1%), 134 (26.4%), 121 (23.9%), and 150 (29.6%) students from the 3rd, 4th, 5th, and 6th year, respectively. Of these, 338 (66.6%) students reported that the COVID-19 pandemic had influenced their choice of training hospitals. The degree of the influence varied based on the university region and the student year. However, most of the students (473, 93.3%) did not change their course for clinical, basic research, or administrative pathways due to the COVID-19 pandemic. Among the clinically oriented students, 391 (77.2%) did not change their preferred speciality.

Conclusions

The COVID-19 pandemic influenced medical students’ choice of training hospitals. Although many students believed that the pandemic would not change their career choices, our results indicate a potential subconscious trend to avoid internal medicine, which is the speciality most directly involved in treating patients with COVID-19.

DOI： 10.1186/s12909-023-05021-6

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Other Link： https://link.springer.com/article/10.1186/s12909-023-05021-6/fulltext.html

A Mediastinum Tumor Presenting With Dysphagia Reviewed

Koichiro Yamamoto, Fumio Otsuka

JCEM Case Reports 2024.1

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

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

成人成長ホルモン分泌不全症に関する医療者教育と総合診療科における実践 Reviewed

越智可奈子, 徳増一樹, 中野靖浩, 須山敦仁, 副島佳晃, 大塚勇輝, 安田美帆, 小比賀美香子, 大塚文男

日本病院総合診療医学会雑誌 20 ( 1 ) 7 - 17 2024.1

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

Koji Iio, Hideharu Hagiya, Tsukasa Higashionna, Fumio Otsuka

New Microbiol. 348 - 353 2024.1

COVID-19流行が内分泌検査数に与えた変化 Reviewed

大塚勇輝, 古川雅規, 東影明人, 大塚文男

日本病院総合診療医学会雑誌 20 ( 1 ) 18 - 21 2024.1

成人成長ホルモン分泌不全症に関する医療者教育と総合診療科における実践

越智可奈子, 徳増一樹, 中野靖浩, 須山敦仁, 副島佳晃, 大塚勇輝, 安田美帆, 小比賀美香子, 大塚文男

日本病院総合診療医学会雑誌 20 ( 1 ) 7 - 17 2024.1

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

成人成長ホルモン分泌不全症(AGHD)は下垂体前葉機能低下症の中で成長ホルモン(GH)不足により様々な代謝異常をきたす疾患である。治療にはGH製剤の自己注射を要することから,患者の予後改善にはAGHDの早期診断・治療とともに多職種連携や患者教育が重要である。本研究では,AGHD診療における多職種での医療連携や専門医の育成を目的とし,AGHDに関する講義や専攻医に対するAGHD患者のマネジメント指導において,その教育効果を検討した。まず多職種へのAGHD教育実践と効果の検討として,医師・看護師・検査技師・医薬情報担当者・医学生・看護学生・医療技術専門学生(作業療法学科・理学療法学科)に対してAGHDに関する講義を行い,講義前後でAGHDの理解度を評価する目的でアンケートを実施した。アンケート内容を(1)基礎的事項,(2)合併症に関する事項,(3)診断に関する事項,(4)治療・マネジメントに関する事項の4分野に分類して検討したところ,全職種において講義後の正答率が上昇し,各職種の正答率上昇率は分野ごとに違いを認めた。次に,内科専攻医に対してのAGHD診療の実践教育を内科専攻医4名に対して行い,AGHDの新規患者における診断・治療・GH自己注射指導およびマネジメント教育を実施し評価を行った。GH自己注射指導に関しては,自己注射練習用器材を用いて実践的トレーニングを行ったところ,全専攻医において診療能の向上を認めた。AGHD患者の診断やGH自己注射を含めた治療継続においては多職種連携や専門医育成などの医療者教育が非常に重要である。診療においては総合診療科における全人的・総合的診療の一環としての教育実践により,医療者のAGHD診療に対する理解が向上しており教育効果が示された。(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=20240228380002&doc_link_id=%2Ffg3byoin%2F2024%2F002001%2F003%2F0007-0017%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Ffg3byoin%2F2024%2F002001%2F003%2F0007-0017%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

COVID-19流行が内分泌検査数に与えた変化

大塚勇輝, 古川雅規, 東影明人, 大塚文男

日本病院総合診療医学会雑誌 20 ( 1 ) 18 - 21 2024.1

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(COVID-19)の流行に伴い医療へのアクセスが制限されたが,本邦において臨床検査に与えた影響については明らかとなっていない。2017年から2022年までの6年間に岡山大学病院において測定された内分泌検査測定件数を経年的に比較すると,入院・外来ともにCOVID-19禍の3年間ではそれ以前に比してACTH・Cortisol,GH・IGFIの測定件数は増加していた一方で,TSHや遊離T4,Renin活性(PRA)やAldosterone(Aldo)の件数は減少しており,特に外来における変化はTSH(平均値:19173件vs17512件),PRA(322件vs251件),Aldo(472件vs306件)と有意であった。内分泌疾患を有す,或いは疑われる患者に対する対面診療での測定依頼が減ったことや,倦怠感など機能低下で生じうる症状を呈する患者が増えたことがその要因ではないかと考察された。COVID-19の流行が少なくとも部分的に本邦での医療の質に影響を与えた可能性が示唆され,その要因分析が今後の課題と思われた。(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=20240228380003&doc_link_id=%2Ffg3byoin%2F2024%2F002001%2F004%2F0018-0021%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Ffg3byoin%2F2024%2F002001%2F004%2F0018-0021%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

シリーズ「一目瞭然！目で診る症例」問題編

中本健太, 萩谷英大, 林瑠衣子, 大塚文男

日本内科学会雑誌 113 127 - 130 2024

「新型コロナウイルス感染症罹患後症状における睡眠障害の特徴と推移」 Reviewed

大塚文男, 砂田匠彦, 大塚勇輝, 徳増一樹, 本多寛之, 古川雅規

日本病院総合診療医学会雑誌 20(3) 129 - 134 2024

Functional interaction of Clock genes and bone morphogenetic proteins in the adrenal cortex. Reviewed International journal

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

Vitamins and hormones 124 429 - 447 2024

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

The bone morphogenetic protein (BMP) system in the adrenal cortex plays modulatory roles in the control of adrenocortical steroidogenesis. BMP-6 enhances aldosterone production by modulating angiotensin (Ang) II-mitogen-activated protein kinase (MAPK) signaling, whereas activin regulates the adrenocorticotropin (ACTH)-cAMP cascade in adrenocortical cells. A peripheral clock system in the adrenal cortex was discovered and it has been shown to have functional roles in the adjustment of adrenocortical steroidogenesis by interacting with the BMP system. It was found that follistatin, a binding protein of activin, increased Clock mRNA levels, indicating an endogenous function of activin in the regulation of Clock mRNA expression. Elucidation of the interrelationships among the circadian clock system, the BMP system and adrenocortical steroidogenesis regulated by the hypothalamic-pituitary-adrenal (HPA) axis would lead to an understanding of the pathophysiology of adrenal disorders and metabolic disorders and the establishment of better medical treatment from the viewpoint of pharmacokinetics.

DOI： 10.1016/bs.vh.2023.05.002

PubMed

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