Faculty Profiles - TOKUMASU Kazuki

Papers - TOKUMASU Kazuki

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Processes of increasing medical residents' intrinsic motivation: a qualitative study. Reviewed International journal

Kazuki Tokumasu, Mikako Obika, Haruo Obara, Makoto Kikukawa, Yoshito Nishimura, Fumio Otsuka

International journal of medical education 13 ( Suppl. ) 115 - 123 2022.4

Authorship：Lead author,　Corresponding author Language：English Publisher：INT JOURNAL MEDICAL EDUCATION-IJML

Objectives: This study aimed to determine qualitatively how medical residents develop intrinsic motivation to learn and work in clinical training settings. Methods: This study was a descriptive qualitative study, which is widely used in healthcare research. We conducted a semi-structured interview aimed to explore key participants' in-depth experiences and perspectives regarding intrinsic motivation. The authors interviewed seven postgraduate Japanese medical residents. The transcripts were analyzed using the sequential and thematic qualitative data analysis technique steps for coding and theorization, which entails coding steps from open to selective, writing a storyline using the final selective codes, and offering theories. Results: External stimulations (a self-handle environment and a near-peer role model) triggered the medical residents' cognitive process (gap recognition, awareness, and internalization) to intrinsic motivation. The residents' awareness of autonomy, responsibility, and independence played a vital role in this process. Furthermore, a psychological feeling of competence also reinforced their intrinsic motivation. Positive feedback and approval from attending physicians and patients' gratitude promoted residents' sense of competence. Conclusions: We illustrated a process for increasing medical residents' intrinsic motivation. The intrinsic motivation was triggered by external stimulations (a self-handle environment and a near-peer role model), which caused the cognitive process: gap recognition, awareness of important attitudes as a doctor (autonomy, responsibility, and independence), and internalization. Since the first step of this process was an external factor, there are potential benefits of designing an appropriate training environment for increasing medical residents' intrinsic motivation.

DOI： 10.5116/ijme.6250.1017

Impact of Lifestyle Changes on Body Weight Gain During Nationwide Lockdown Due to COVID-19 Pandemic. International journal

Chisa Nishida, Hiroyuki Honda, Yuki Otsuka, Hideharu Hagiya, Yasuhiro Nakano, Kohei Oguni, Kazuki Tokumasu, Yasue Sakurada, Mikako Obika, Fumio Otsuka

Journal of clinical medicine 14 ( 7 ) 2025.3

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

Background: During the coronavirus disease 2019 (COVID-19) pandemic, people in Japan were urged to stay at home as much as possible, and this resulted in significant changes in lifestyle behavior. The new lifestyle included factors affecting both energy intake and energy consumption, and it is now thought that weight gain during the lockdown was the result of complex effects. The aim of this study was to determine the relationships among lifestyle habits, laboratory data, and body weight gain during the lockdown using medical check-up data. Methods: A total of 3789 individuals who had undergone consecutive medical check-ups during the period from 2018 to 2020 were included in this study. Participants whose body weight had increased by 5% or more were divided into two groups: a before-lockdown group (participants who had gained weight between 2018 and 2019) and an after-lockdown group (participants who had gained weight between 2019 and 2020). Physical measurements, laboratory data, and answers to six questions about lifestyle habits, for which information was obtained from the records from medical check-ups, were compared in the two groups. Results: There was no significant difference between the distribution of weight changes in 2018-2019 before the lockdown and the distribution of weight changes in 2019-2020 after the lockdown. The before-lockdown and after-lockdown groups both included about 7% of the total participants (279 and 273 participants, respectively). Diastolic blood pressure and levels of AST, ALT, and LDL-C were significantly higher in the after-lockdown group than in the before-lockdown group. The percentages of participants with alcohol consumption and exercise habits were significantly higher in the after-lockdown group than in the before-lockdown group, and an analysis by gender showed that the differences were significant for women but not for men. Conclusions: The distributions of weight changes before and during the COVID-19 pandemic were similar. Exercise habits and alcohol consumption might have been unique factors causing weight gain during the COVID-19 pandemic, particularly in women. Our findings suggest that the impact of behavioral restrictions and lifestyle changes during a pandemic may be different in men and women.

DOI： 10.3390/jcm14072242

Involvement of a Novel Variant of FGFR1 Detected in an Adult Patient with Kallmann Syndrome in Regulation of Gonadal Steroidogenesis. Reviewed International journal

Yoshiaki Soejima, Yuki Otsuka, Marina Kawaguchi, Kohei Oguni, Koichiro Yamamoto, Yasuhiro Nakano, Miho Yasuda, Kazuki Tokumasu, Keigo Ueda, Kosei Hasegawa, Nahoko Iwata, Fumio Otsuka

International journal of molecular sciences 26 ( 6 ) 2025.3

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

Fibroblast growth factor receptor 1 (FGFR1), also known as KAL2, is a tyrosine kinase receptor, and variants of FGFR1 have been detected in patients with Kallmann syndrome (KS), which is a congenital developmental disorder characterized by central hypogonadism and anosmia. Herein, we report an adult case of KS with a novel variant of FGFR1. A middle-aged male was referred for a compression fracture of a lumbar vertebra. It was shown that he had severe osteoporosis, anosmia, gynecomastia, and a past history of operations for cryptorchidism. Endocrine workup using pituitary and gonadal stimulation tests revealed the presence of both primary and central hypogonadism. Genetic testing revealed a novel variant of FGFR1 (c.2197_2199dup, p.Met733dup). To identify the pathogenicity of the novel variant and the clinical significance for the gonads, we investigated the effects of the FGFR1 variant on the downstream signaling of FGFR1 and gonadal steroidogenesis by using human steroidogenic granulosa cells. It was revealed that the transfection of the variant gene significantly impaired FGFR1 signaling, detected through the downregulation of SPRY2, compared with that of the case of the forced expression of wild-type FGFR1, and that the existence of the variant gene apparently altered the expression of key steroidogenic factors, including StAR and aromatase, in the gonad. The results suggested that the novel variant of FGFR1 detected in the patient with KS was linked to the impairment of FGFR1 signaling, as well as the alteration of gonadal steroidogenesis, leading to the pathogenesis of latent primary hypogonadism.

DOI： 10.3390/ijms26062713

Course of General Fatigue in Patients with Post-COVID-19 Conditions Who Were Prescribed Hochuekkito: A Single-Center Exploratory Pilot Study. Reviewed International journal

Kazuki Tokumasu, Nobuyoshi Matsuki, Yuki Otsuka, Yoko Sakamoto, Keigo Ueda, Yui Matsuda, Yasue Sakurada, Hiroyuki Honda, Yasuhiro Nakano, Toru Hasegawa, Ryosuke Takase, Daisuke Omura, Fumio Otsuka

Journal of clinical medicine 14 ( 4 ) 2025.2

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

Background: After the start of the COVID-19 pandemic, general fatigue in patients with long COVID and post-COVID-19 conditions (PCC) became a medical issue. Although there is a lack of evidence-based treatments, Kampo medicine (traditional Japanese medicine) has gained attention in Japan. At an outpatient clinic in Japan specializing in long COVID, 24% of all prescriptions were Kampo medicines, and 72% of Kampo medicine prescriptions were hochuekkito. However, there has been no prospective, quantitative study on the course of fatigue in patients with long COVID and PCC who were prescribed hochuekkito. The aim of this study was to clarify the course of fatigue in those patients. Methods: This study included patients aged 18 years or older with general fatigue who visited the long COVID specialized outpatient clinic at Okayama University Hospital and consented to participate after being prescribed hochuekkito. We reviewed the backgrounds of the patients, and we evaluated the patients' fatigue assessment scale in person or online. Results: Twenty patients were enrolled in this study from September to December in 2023. The average age of the patients was 42.9 years (SD: 15.8 years) and 12 patients (60%) were female. After hochuekkito administration, the fatigue assessment scale score decreased from 35.9 (SD: 5.9) at the initial visit to 31.2 (SD: 9.4) after 8 weeks, indicating a trend for improvement in fatigue (difference: 4.7; 95% CI: 0.5-8.9). Conclusions: A trend for improvement in fatigue was observed in patients with long COVID and PCC who were prescribed hochuekkito, indicating a potential benefit of hochuekkito for general fatigue in such patients. General fatigue in patients with long COVID or PCC can be classified as post-infectious fatigue syndrome and is considered a condition of qi deficiency in Kampo medicine, for which hochuekkito is appropriately indicated.

DOI： 10.3390/jcm14041391

Interrelationships Between Plasma Levels of Brain Natriuretic Peptide and Prolonged Symptoms Due to Long COVID. Reviewed International journal

Yohei Masuda, Yuki Otsuka, Kazuki Tokumasu, Hiroyuki Honda, Yasue Sakurada, Yui Matsuda, Yasuhiro Nakano, Ryosuke Takase, Daisuke Omura, Toru Hasegawa, Keigo Ueda, Fumio Otsuka

Journal of clinical medicine 14 ( 3 ) 2025.1

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

Objectives: Evidence for the usefulness of biomarkers that aid in diagnosis, assessment of severity, and prediction of prognosis in patients with long COVID is limited. The aim of this study was to clarify the characteristics of brain natriuretic peptide (BNP) in long COVID. Methods: We conducted a retrospective observational study of patients who visited the COVID-19 aftercare outpatient clinic at Okayama University Hospital from February 2021 to April 2024. Results: A total of 428 patients were enrolled in this study, and the patients were divided into a group with normal BNP (n = 314, ≤18.4 pg/mL) and a group with increased BNP (n = 114, >18.4 pg/mL). The long COVID group with increased BNP had a higher proportion of females (44.3% vs. 73.7%, p < 0.01) and an older median age (38 vs. 51 years, p < 0.01). Fatigue and brain fog were commonly manifested in both groups, while dyspnea was a more frequent complaint in the group with increased BNP. Various symptoms including fatigue, palpitations, and taste and/or olfactory disorders were associated with elevated BNP (23 to 24 pg/mL). Memory impairment was also linked to higher BNP (OR: 2.36, p = 0.05). In long COVID patients, plasma BNP elevation appears to be more pronounced in females and is often related to cardiogenic factors, in which inflammatory responses are also involved. Conclusions: Plasma BNP measurement may be useful for evaluating the severity of long COVID, especially in female patients and those with respiratory symptoms and/or memory impairment.

DOI： 10.3390/jcm14030817

What medical students and residents learned from reflection through patients' perspectives: a qualitative study. Reviewed International journal

Kazuki Tokumasu, Puthiery Va, Haruo Obara, Lisa Rucker

International journal of medical education 15 150 - 158 2024.12

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

OBJECTIVES: The purposes of this study were to identify reflective processes from patients' points of view for difficult patient-doctor interactions and learn how the processes made medical students and residents aware of their own medical practice. These processes were compared in two countries (US and Japan). METHODS: The study was a descriptive qualitative study utilizing semi-structured interviews. Participants were from US and Japan. We analyzed the data using reflective thematic analysis of the implementation of reflections (from a patient's point of view) into medical clinical education and training from a constructivism paradigm. RESULTS: We included twenty participants each from US and Japan by convenience sampling. The participants were medical students during clinical clerkship and post graduate year-1, 2, and 3 medical residents. Medical students and residents realized four cognitions (different expectations of patients and doctors, language communication barrier, time restriction and healthcare system challenges) from reflections from patients' perspectives. Subsequently, medical students and residents identified three types of awareness (appropriate communication, empathy, and patient-doctor relationship of trust). During these reflections from patients' perspectives, the medical students and residents had a willingness to change future behavior. CONCLUSIONS: This study revealed one aspect of medical students' and residents' cognitions and awareness of clinical experiences through reflection from patients' perspectives. This cognitive process aligns the ideas of medical students and residents more closely with the patients' perceptions and influences their willingness to change their behavior. This process enables comprehensive realization in person-centered care.

DOI： 10.5116/ijme.6741.f16c

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

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

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

圧迫骨折と女性化乳房を契機に精査し、AGHDを合併した新規KAL2バリアントによるKallmann症候群と診断しえた1例

副島佳晃, 大塚勇輝, 川口満理奈, 大國皓平, 中野靖浩, 安田美帆, 徳増一樹, 植田圭吾, 長谷川高誠, 大塚文男

日本内分泌学会雑誌 100 ( 4 ) 1077 - 1077 2024.12

Comparative Analysis of Diagnostic Performance: Differential Diagnosis Lists by LLaMA3 Versus LLaMA2 for Case Reports Reviewed International journal

Takanobu Hirosawa, Yukinori Harada, Kazuki Tokumasu, Tatsuya Shiraishi, Tomoharu Suzuki, Taro Shimizu

JMIR Formative Research 8 e64844 - e64844 2024.11

Language：English Publishing type：Research paper (scientific journal) Publisher：JMIR Publications Inc.

Background

Generative artificial intelligence (AI), particularly in the form of large language models, has rapidly developed. The LLaMA series are popular and recently updated from LLaMA2 to LLaMA3. However, the impacts of the update on diagnostic performance have not been well documented.

Objective

We conducted a comparative evaluation of the diagnostic performance in differential diagnosis lists generated by LLaMA3 and LLaMA2 for case reports.

Methods

We analyzed case reports published in the American Journal of Case Reports from 2022 to 2023. After excluding nondiagnostic and pediatric cases, we input the remaining cases into LLaMA3 and LLaMA2 using the same prompt and the same adjustable parameters. Diagnostic performance was defined by whether the differential diagnosis lists included the final diagnosis. Multiple physicians independently evaluated whether the final diagnosis was included in the top 10 differentials generated by LLaMA3 and LLaMA2.

Results

In our comparative evaluation of the diagnostic performance between LLaMA3 and LLaMA2, we analyzed differential diagnosis lists for 392 case reports. The final diagnosis was included in the top 10 differentials generated by LLaMA3 in 79.6% (312/392) of the cases, compared to 49.7% (195/392) for LLaMA2, indicating a statistically significant improvement (P<.001). Additionally, LLaMA3 showed higher performance in including the final diagnosis in the top 5 differentials, observed in 63% (247/392) of cases, compared to LLaMA2’s 38% (149/392, P<.001). Furthermore, the top diagnosis was accurately identified by LLaMA3 in 33.9% (133/392) of cases, significantly higher than the 22.7% (89/392) achieved by LLaMA2 (P<.001). The analysis across various medical specialties revealed variations in diagnostic performance with LLaMA3 consistently outperforming LLaMA2.

Conclusions

The results reveal that the LLaMA3 model significantly outperforms LLaMA2 per diagnostic performance, with a higher percentage of case reports having the final diagnosis listed within the top 10, top 5, and as the top diagnosis. Overall diagnostic performance improved almost 1.5 times from LLaMA2 to LLaMA3. These findings support the rapid development and continuous refinement of generative AI systems to enhance diagnostic processes in medicine. However, these findings should be carefully interpreted for clinical application, as generative AI, including the LLaMA series, has not been approved for medical applications such as AI-enhanced diagnostics.

DOI： 10.2196/64844

Effectiveness of the educational training program for Japanese chief residents: A one‐year pilot study

Toshinori Nishizawa, Kazuya Nagasaki, Kazuki Tokumasu, Shunsuke Kosugi, Tadayuki Hashimoto, Kosuke Tanaka, Koma Hotta, Sho Isoda, Aiko Harada, Shinya Ishigame, Takuma Hata, Masayuki Nogi

Journal of General and Family Medicine 26 ( 1 ) 100 - 105 2024.10

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

Abstract

Background

Multi‐institutional faculty development programs for chief residents were lacking in Japan. This study evaluated the effectiveness of the program for enhancing the knowledge and behaviors of chief residents at the national level.

Methods

Six participants completed self‐assessment questionnaires at three points: before, immediately after, and 6 months post‐program. Knowledge and behavior changes were compared using the Mann–Whitney U test.

Results

Significant improvements in knowledge were observed and maintained at 6 months. However, behavioral changes were limited, with significant improvements only in counseling skills.

Conclusion

The program effectively increased knowledge but faced challenges in translating it into sustained behavioral change.

DOI： 10.1002/jgf2.744

Comparative Study to Evaluate the Accuracy of Differential Diagnosis Lists Generated by Gemini Advanced, Gemini, and Bard for a Case Report Series Analysis: Cross-Sectional Study Reviewed International journal

Takanobu Hirosawa, Yukinori Harada, Kazuki Tokumasu, Takahiro Ito, Tomoharu Suzuki, Taro Shimizu

JMIR Medical Informatics 12 e63010 - e63010 2024.10

Language：English Publishing type：Research paper (scientific journal) Publisher：JMIR Publications Inc.

Background

Generative artificial intelligence (GAI) systems by Google have recently been updated from Bard to Gemini and Gemini Advanced as of December 2023. Gemini is a basic, free-to-use model after a user’s login, while Gemini Advanced operates on a more advanced model requiring a fee-based subscription. These systems have the potential to enhance medical diagnostics. However, the impact of these updates on comprehensive diagnostic accuracy remains unknown.

Objective

This study aimed to compare the accuracy of the differential diagnosis lists generated by Gemini Advanced, Gemini, and Bard across comprehensive medical fields using case report series.

Methods

We identified a case report series with relevant final diagnoses published in the American Journal Case Reports from January 2022 to March 2023. After excluding nondiagnostic cases and patients aged 10 years and younger, we included the remaining case reports. After refining the case parts as case descriptions, we input the same case descriptions into Gemini Advanced, Gemini, and Bard to generate the top 10 differential diagnosis lists. In total, 2 expert physicians independently evaluated whether the final diagnosis was included in the lists and its ranking. Any discrepancies were resolved by another expert physician. Bonferroni correction was applied to adjust the P values for the number of comparisons among 3 GAI systems, setting the corrected significance level at P value <.02.

Results

In total, 392 case reports were included. The inclusion rates of the final diagnosis within the top 10 differential diagnosis lists were 73% (286/392) for Gemini Advanced, 76.5% (300/392) for Gemini, and 68.6% (269/392) for Bard. The top diagnoses matched the final diagnoses in 31.6% (124/392) for Gemini Advanced, 42.6% (167/392) for Gemini, and 31.4% (123/392) for Bard. Gemini demonstrated higher diagnostic accuracy than Bard both within the top 10 differential diagnosis lists (P=.02) and as the top diagnosis (P=.001). In addition, Gemini Advanced achieved significantly lower accuracy than Gemini in identifying the most probable diagnosis (P=.002).

Conclusions

The results of this study suggest that Gemini outperformed Bard in diagnostic accuracy following the model update. However, Gemini Advanced requires further refinement to optimize its performance for future artificial intelligence–enhanced diagnostics. These findings should be interpreted cautiously and considered primarily for research purposes, as these GAI systems have not been adjusted for medical diagnostics nor approved for clinical use.

DOI： 10.2196/63010

COVID-19罹患後症状の患者における就労状況への影響

松田祐依, 櫻田泰江, 大塚勇輝, 徳増一樹, 中野靖浩, 砂田匠彦, 本多寛之, 長谷川徹, 高瀬了輔, 大村大輔, 植田圭吾, 大塚文男

日本病院総合診療医学会雑誌 20 ( 臨増2 ) 263 - 263 2024.9

COVID-19罹患後症状の女性患者にみられる月経異常とストレスの関係

櫻田泰江, 松田祐依, 長谷川徹, 大塚勇輝, 中野靖浩, 徳増一樹, 砂田匠彦, 本橋花音, 本多寛之, 植田圭吾, 大塚文男

日本病院総合診療医学会雑誌 20 ( 臨増2 ) 263 - 263 2024.9

Postgraduate Year Two Medical Residents' Awareness of Personal Development as a Physician during the Management of Inpatients: A Qualitative Study. Reviewed International journal

Kazuki Tokumasu, Haruo Obara, Takanobu Hirosawa, Hiroko Ogawa, Fumio Otsuka

Healthcare (Basel, Switzerland) 12 ( 16 ) 2024.8

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

Clinical experiences, helping relationships, and reflection are key factors for personal development for physicians. However, few studies have shown which experiences are important for personal growth and how medical residents specifically use their experiences for personal growth. The aim of this study was to identify from the medical residents' perspective which clinical experiences contribute to their personal development. We employed a qualitative design, conducting semi-structured interviews with ten postgraduate year two medical residents at a Japanese teaching hospital. The interviews were transcribed in interview memos, anonymized, and subjected to reflective thematic analysis to generate themes relevant to personal and professional development. Successful clinical experiences with autonomy and responsibility in clinical management were shown to be essential points for personal development as a physician. Autonomy in this study was the attitude of making one's own choices when managing patients. Responsibility was the obligation of the resident to take charge of a patient. Instructing junior trainees, appreciation received from patients, and approval granted by attending physicians reinforced their feelings of personal growth. The realization of what experiences and concepts influence medical residents' personal growth and development will make their professional development more effective.

DOI： 10.3390/healthcare12161621

Clinical and endocrine features of orthostatic intolerance detected in patients with long COVID. Reviewed International journal

Atsushi Kato, Kazuki Tokumasu, Koichiro Yamamoto, Yuki Otsuka, Yasuhiro Nakano, Hiroyuki Honda, Naruhiko Sunada, Yasue Sakurada, Yui Matsuda, Toru Hasegawa, Ryosuke Takase, Keigo Ueda, Fumio Otsuka

Scientific reports 14 ( 1 ) 17025 - 17025 2024.7

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

Orthostatic intolerance (OI) is a key symptom of long COVID; however, the pathophysiology remains unknown. Among 688 long COVID patients who visited our clinic during the period from February 2021 to April 2023, 86 patients who were suspected of having OI and who underwent an active standing test (ST) were investigated to elucidate the clinical characteristics of OI in patients with long COVID. Of the 86 patients, 33 patients (38%) were ST-positive. Nausea and tachycardia in daily life were frequent complaints in the ST-positive group. The increase in heart rate (HR) during the ST was significantly greater during a 10-min period after standing in the ST-positive group (+ 30 bpm) than in the ST-negative group (+ 16 bpm). The initial increase in diastolic blood pressure (DBP) just after standing was significantly greater in the ST-positive group (+ 14 mmHg) than in the ST-negative group (+ 9 mmHg). Serum cortisol levels in the ST-positive patients aged over 20 years were higher and growth hormone levels in the patients under 20 years of age were lower than those in the ST-negative group. Autonomous nervous symptoms, transient DBP rise with increasing HR after standing, and endocrine dysfunctions are helpful for detecting OI related to long COVID.

DOI： 10.1038/s41598-024-67815-y

Reliability and Validity of the Japanese Version of the Fatigue Assessment Scale. Reviewed

Kazuki Tokumasu, Nobuyoshi Matsuki, Hirohisa Fujikawa, Yoko Sakamoto, Fumio Otsuka

Internal medicine (Tokyo, Japan) 2024.7

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

Objective General fatigue is one of the most frequent chief complaints in primary care, and an accurate assessment of fatigue has a direct impact on a patient's quality of life and treatment decisions. The Fatigue Assessment Scale (FAS), a measure of general fatigue, is useful for assessing fatigue in diverse cultures and diseases. However, there has been no study showing the reliability and validity of the scale in the Japanese context. The present study assessed the reliability and validity of the Japanese version of the FAS. Methods This study was conducted on 649 patients with long COVID who had a high frequency of general fatigue. To test the structural validity of the FAS, the patients were randomly divided into two groups: one in which an exploratory factor analysis (EFA) was conducted and one in which a confirmatory factor analysis (CFA) was conducted. Cronbach's alpha was calculated to assess internal consistency reliability. Results As 58 patients had missing values, we analyzed the data of 591 patients. The EFA led to an FAS comprising two factors. The CFA showed an acceptable fit for this two-factor model. The internal consistency was found to be good (Cronbach's alpha =0.89). Conclusion This study verified the structural validity and internal consistency and reliability of the Japanese version of the FAS. The results indicate that the Japanese version of the FAS is useful for assessing general fatigue in patients with long COVID in Japan.

DOI： 10.2169/internalmedicine.4101-24

Importance of Blood Glucose Measurement for Predicting the Prognosis of Long COVID: A Retrospective Study in Japan. Reviewed International journal

Sho Yokoyama, Hiroyuki Honda, Yuki Otsuka, Kazuki Tokumasu, Yasuhiro Nakano, Yasue Sakurada, Yui Matsuda, Naruhiko Sunada, Toru Hasegawa, Ryosuke Takase, Daisuke Omura, Yoshiaki Soejima, Keigo Ueda, Masayuki Kishida, Fumio Otsuka

Journal of clinical medicine 13 ( 14 ) 2024.7

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

Purpose: The present study aimed to clarify the effects of a hyperglycemic condition on the clinical consequences of long COVID. Methods: Among 643 patients who visited the outpatient clinic of our hospital from February 2021 to September 2023, long COVID patients were classified into a hyperglycemic (HG) group with casual blood glucose levels above 140 mg/dL and a normoglycemic (NG) group. The patients' backgrounds, clinical symptoms, health status including the QOL evaluation scale (EQ-5D-5L), self-rating depression scale (SDS), and F-scale questionnaire (FSSG), blood test data, and recovery periods were analyzed. Results: The NG group included 607 patients with long COVID and the HG group included 36 patients with long COVID. Patients in the HG group were older than those in the NG group (55 vs. 41 years; p < 0.001) and included a larger percentage of males (67% vs. 44%; p = 0.009). The HG group had a larger percentage of patients with moderate-to-severe conditions in the acute infection phase (28% vs. 12%; p = 0.008), a higher BMI (25 vs. 22 kg/m2; p < 0.001), higher blood pressure (138/81 vs. 122/72 mmHg; p < 0.001), and a larger percentage of patients with an alcohol drinking habit (53% vs. 34%; p = 0.031). Long COVID symptoms and self-rated scales were not differed between the two groups; however, the laboratory data showed that liver and renal functions and metabolic data were significantly worse in the HG group. Although there was no apparent difference between the two groups in duration from the infection to the first visit, the HG group had a significantly longer period of recovery from long COVID (median period of 421 vs. 294 days; p = 0.019). Conclusion: A hyperglycemic state associated with other lifestyle-related diseases is associated with the prolongation of recovery from long COVID.

DOI： 10.3390/jcm13144099

Changes in Working Situations of Employed Long COVID Patients: Retrospective Study in Japanese Outpatient Clinic. Reviewed International journal

Yui Matsuda, Yasue Sakurada, Yuki Otsuka, Kazuki Tokumasu, Yasuhiro Nakano, Naruhiko Sunada, Hiroyuki Honda, Toru Hasegawa, Ryosuke Takase, Daisuke Omura, Keigo Ueda, Fumio Otsuka

Journal of clinical medicine 13 ( 13 ) 2024.6

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

Purpose: The present study aimed to uncover the impact of long COVID on the working situations of Japanese patients. Methods: Changes in the working situations of the patients who visited our long COVID clinic were evaluated from medical records for the aspects of physical status, quality of life (QOL), and mental conditions. Results: Of 846 long COVID patients who visited our clinic from February 2021 to December 2023, 545 employed patients aged between 18 and 65 years were included in this study. A total of 295 patients (54.1%) with long COVID (median age: 43 years, female: 55.6%) experienced changes in their working status. Those patients included 220 patients (40.4%) who took a leave of absence, 53 patients (9.7%) who retired, and 22 patients (4%) with reduced working hours. Most of the patients (93.2%) with changes in working conditions had mild disease severity in the acute phase of COVID-19. The majority of those patients with mild disease severity (58.8%) were infected in the Omicron-variant phase and included 65.3% of the female patients. The major symptoms in long COVID patients who had changes in their working situations were fatigue, insomnia, headache, and dyspnea. Scores indicating fatigue and QOL were worsened in long COVID patients who had changes in their working situations. In addition, 63.7% of the long COVID patients with changes in their working situations had decreases in their incomes. Conclusions: Changes in the working situation of long COVID patients who were employed had a negative impact on the maintenance of their QOL.

DOI： 10.3390/jcm13133809

Evaluating ChatGPT-4’s Accuracy in Identifying Final Diagnoses Within Differential Diagnoses Compared With Those of Physicians: Experimental Study for Diagnostic Cases Reviewed International journal

Takanobu Hirosawa, Yukinori Harada, Kazuya Mizuta, Tetsu Sakamoto, Kazuki Tokumasu, Taro Shimizu

JMIR Formative Research 8 e59267 - e59267 2024.6

Language：English Publishing type：Research paper (scientific journal) Publisher：JMIR Publications Inc.

Background

The potential of artificial intelligence (AI) chatbots, particularly ChatGPT with GPT-4 (OpenAI), in assisting with medical diagnosis is an emerging research area. However, it is not yet clear how well AI chatbots can evaluate whether the final diagnosis is included in differential diagnosis lists.

Objective

This study aims to assess the capability of GPT-4 in identifying the final diagnosis from differential-diagnosis lists and to compare its performance with that of physicians for case report series.

Methods

We used a database of differential-diagnosis lists from case reports in the American Journal of Case Reports, corresponding to final diagnoses. These lists were generated by 3 AI systems: GPT-4, Google Bard (currently Google Gemini), and Large Language Models by Meta AI 2 (LLaMA2). The primary outcome was focused on whether GPT-4’s evaluations identified the final diagnosis within these lists. None of these AIs received additional medical training or reinforcement. For comparison, 2 independent physicians also evaluated the lists, with any inconsistencies resolved by another physician.

Results

The 3 AIs generated a total of 1176 differential diagnosis lists from 392 case descriptions. GPT-4’s evaluations concurred with those of the physicians in 966 out of 1176 lists (82.1%). The Cohen κ coefficient was 0.63 (95% CI 0.56-0.69), indicating a fair to good agreement between GPT-4 and the physicians’ evaluations.

Conclusions

GPT-4 demonstrated a fair to good agreement in identifying the final diagnosis from differential-diagnosis lists, comparable to physicians for case report series. Its ability to compare differential diagnosis lists with final diagnoses suggests its potential to aid clinical decision-making support through diagnostic feedback. While GPT-4 showed a fair to good agreement for evaluation, its application in real-world scenarios and further validation in diverse clinical environments are essential to fully understand its utility in the diagnostic process.

DOI： 10.2196/59267

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 2024.5

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

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

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

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 30 ( 3 ) 236 - 241 2024.3

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

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

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

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

Clinical decision support system using a machine learning model to assist simultaneous cardiopulmonary auscultation: Open-label randomized controlled trial. Reviewed International journal

Takanobu Hirosawa, Tetsu Sakamoto, Yukinori Harada, Kazuki Tokumasu, Taro Shimizu

Digital health 10 20552076241233689 - 20552076241233689 2024.1

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

Background

The utility of a clinical decision support system using a machine learning (ML) model for simultaneous cardiac and pulmonary auscultation is unknown.

Objective

This study aimed to develop and evaluate an ML system's utility for cardiopulmonary auscultation.

Methods

First, we developed an ML system for cardiopulmonary auscultation, using cardiopulmonary sound files from our previous study. The technique involved pre-processing, feature extraction, and classification through several neural network layers. After integration, the output class was categorized as “normal,” “abnormal,” or “undetermined.” Second, we evaluated the ML system with 24 junior residents in an open-label randomized controlled trial at a university hospital. Participants were randomly assigned to the ML system group (intervention) or conventional auscultation group (control). During training, participants listened to four cardiac and four pulmonary sounds, all of which were correctly classified. Then, participants classified a series of 16 simultaneous cardiopulmonary sounds. The control group auscultated the sounds using noise-cancelling headphones, while the intervention group did so by watching recommendations from the ML system.

Results

The total scores for correctly identified normal or abnormal cardiopulmonary sounds in the intervention group were significantly higher than those in the control group (366/384 [95.3%] vs. 343/384 [89.3%], P = 0.003). The cardiac test score in the intervention group was better (111/192 [57.8%] vs. 90/192 [46.9%], P = 0.04); there was no significant difference in pulmonary auscultation.

Conclusions

The ML-based system improved the accuracy of cardiopulmonary auscultation for junior residents. This result suggests that the system can assist early-career physicians in accurate screening.

DOI： 10.1177/20552076241233689

Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/20552076241233689

Diagnostic performance of generative artificial intelligences for a series of complex case reports Reviewed International journal

Takanobu Hirosawa, Yukinori Harada, Kazuya Mizuta, Tetsu Sakamoto, Kazuki Tokumasu, Taro Shimizu

DIGITAL HEALTH 10 20552076241265215 - 20552076241265215 2024.1

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

Background

Diagnostic performance of generative artificial intelligences (AIs) using large language models (LLMs) across comprehensive medical specialties is still unknown.

Objective

We aimed to evaluate the diagnostic performance of generative AIs using LLMs in complex case series across comprehensive medical fields.

Methods

We analyzed published case reports from the American Journal of Case Reports from January 2022 to March 2023. We excluded pediatric cases and those primarily focused on management. We utilized three generative AIs to generate the top 10 differential-diagnosis (DDx) lists from case descriptions: the fourth-generation chat generative pre-trained transformer (ChatGPT-4), Google Gemini (previously Bard), and LLM Meta AI 2 (LLaMA2) chatbot. Two independent physicians assessed the inclusion of the final diagnosis in the lists generated by the AIs.

Results

Out of 557 consecutive case reports, 392 were included. The inclusion rates of the final diagnosis within top 10 DDx lists were 86.7% (340/392) for ChatGPT-4, 68.6% (269/392) for Google Gemini, and 54.6% (214/392) for LLaMA2 chatbot. The top diagnoses matched the final diagnoses in 54.6% (214/392) for ChatGPT-4, 31.4% (123/392) for Google Gemini, and 23.0% (90/392) for LLaMA2 chatbot. ChatGPT-4 showed higher diagnostic accuracy than Google Gemini ( P < 0.001) and LLaMA2 chatbot ( P < 0.001). Additionally, Google Gemini outperformed LLaMA2 chatbot within the top 10 DDx lists ( P < 0.001) and as the top diagnosis ( P = 0.010).

Conclusions

This study demonstrated the diagnostic performance of generative AIs including ChatGPT-4, Google Gemini, and LLaMA2 chatbot. ChatGPT-4 exhibited higher diagnostic accuracy than the other platforms. These findings suggest the importance of understanding the differences in diagnostic performance among generative AIs, especially in complex case series across comprehensive medical fields, like general medicine.

DOI： 10.1177/20552076241265215

Other Link： https://journals.sagepub.com/doi/full-xml/10.1177/20552076241265215

Phase-dependent trends in the prevalence of myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) related to long COVID: A criteria-based retrospective study in Japan. International journal

Satoru Morita, Kazuki Tokumasu, Yuki Otsuka, Hiroyuki Honda, Yasuhiro Nakano, Naruhiko Sunada, Yasue Sakurada, Yui Matsuda, Yoshiaki Soejima, Keigo Ueda, Fumio Otsuka

PloS one 19 ( 12 ) e0315385 2024

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

BACKGROUND: The characteristics of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) related to COVID-19 have remained uncertain. To elucidate the clinical trend of ME/CFS induced by long COVID, we examined data for patients who visited our outpatient clinic established in a university hospital during the period from Feb 2021 to July 2023. METHODS: Long COVID patients were classified into two groups, an ME/CFS group and a non-ME/CFS group, based on three diagnostic criteria. RESULTS: The prevalence of ME/CFS in the long COVID patients was 8.4% (62 of 739 cases; female: 51.6%) and factors related to ME/CFS were severe illness, smoking and alcohol drinking habits, and fewer vaccinations. The frequency of ME/CFS decreased from 23.9% in the Preceding period to 13.7% in the Delta-dominant period and to 3.3% in the Omicron-dominant period. Fatigue and headache were commonly frequent complaints in the ME/CFS group, and the frequency of poor concentration in the ME/CFS group was higher in the Omicron period. Serum ferritin levels were significantly higher in female patients in the ME/CFS group infected in the Preceding period. In the ME/CFS group, the proportion of patients complaining of brain fog significantly increased from 22.2% in the Preceding period to 47.9% in the Delta period and to 81.3% in the Omicron period. The percentage of patients who had received vaccination was lower in the ME/CFS group than the non-ME/CFS group over the study period, whereas there were no differences in the vaccination rate between the groups in each period. CONCLUSION: The proportion of long COVID patients who developed ME/CFS strictly diagnosed by three criteria was lower among patients infected in the Omicron phase than among patients infected in the other phases, while the proportion of patients with brain fog inversely increased. Attention should be paid to the variant-dependent trends of ME/CFS triggered by long COVID (300 words).

DOI： 10.1371/journal.pone.0315385

Evaluating ChatGPT-4's Diagnostic Accuracy: Impact of Visual Data Integration (Preprint) Reviewed International journal

Takanobu Hirosawa, Yukinori Harada, Kazuki Tokumasu, Takahiro Ito, Tomoharu Suzuki, Taro Shimizu

JMIR Medical Informatics 12 e55627 2023.12

Language：English Publishing type：Research paper (scientific journal) Publisher：JMIR Publications Inc.

BACKGROUND: In the evolving field of health care, multimodal generative artificial intelligence (AI) systems, such as ChatGPT-4 with vision (ChatGPT-4V), represent a significant advancement, as they integrate visual data with text data. This integration has the potential to revolutionize clinical diagnostics by offering more comprehensive analysis capabilities. However, the impact on diagnostic accuracy of using image data to augment ChatGPT-4 remains unclear. OBJECTIVE: This study aims to assess the impact of adding image data on ChatGPT-4's diagnostic accuracy and provide insights into how image data integration can enhance the accuracy of multimodal AI in medical diagnostics. Specifically, this study endeavored to compare the diagnostic accuracy between ChatGPT-4V, which processed both text and image data, and its counterpart, ChatGPT-4, which only uses text data. METHODS: We identified a total of 557 case reports published in the American Journal of Case Reports from January 2022 to March 2023. After excluding cases that were nondiagnostic, pediatric, and lacking image data, we included 363 case descriptions with their final diagnoses and associated images. We compared the diagnostic accuracy of ChatGPT-4V and ChatGPT-4 without vision based on their ability to include the final diagnoses within differential diagnosis lists. Two independent physicians evaluated their accuracy, with a third resolving any discrepancies, ensuring a rigorous and objective analysis. RESULTS: The integration of image data into ChatGPT-4V did not significantly enhance diagnostic accuracy, showing that final diagnoses were included in the top 10 differential diagnosis lists at a rate of 85.1% (n=309), comparable to the rate of 87.9% (n=319) for the text-only version (P=.33). Notably, ChatGPT-4V's performance in correctly identifying the top diagnosis was inferior, at 44.4% (n=161), compared with 55.9% (n=203) for the text-only version (P=.002, χ2 test). Additionally, ChatGPT-4's self-reports showed that image data accounted for 30% of the weight in developing the differential diagnosis lists in more than half of cases. CONCLUSIONS: Our findings reveal that currently, ChatGPT-4V predominantly relies on textual data, limiting its ability to fully use the diagnostic potential of visual information. This study underscores the need for further development of multimodal generative AI systems to effectively integrate and use clinical image data. Enhancing the diagnostic performance of such AI systems through improved multimodal data integration could significantly benefit patient care by providing more accurate and comprehensive diagnostic insights. Future research should focus on overcoming these limitations, paving the way for the practical application of advanced AI in medicine.

DOI： 10.2196/55627

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

Authorship：Lead author 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

ChatGPT-Generated Differential Diagnosis Lists for Complex Case-Derived Clinical Vignettes: Diagnostic Accuracy Evaluation. Reviewed International journal

Takanobu Hirosawa, Ren Kawamura, Yukinori Harada, Kazuya Mizuta, Kazuki Tokumasu, Yuki Kaji, Tomoharu Suzuki, Taro Shimizu

JMIR medical informatics 11 e48808 2023.10

Language：English Publishing type：Research paper (scientific journal) Publisher：JMIR Publications Inc.

BACKGROUND: The diagnostic accuracy of differential diagnoses generated by artificial intelligence chatbots, including ChatGPT models, for complex clinical vignettes derived from general internal medicine (GIM) department case reports is unknown. OBJECTIVE: This study aims to evaluate the accuracy of the differential diagnosis lists generated by both third-generation ChatGPT (ChatGPT-3.5) and fourth-generation ChatGPT (ChatGPT-4) by using case vignettes from case reports published by the Department of GIM of Dokkyo Medical University Hospital, Japan. METHODS: We searched PubMed for case reports. Upon identification, physicians selected diagnostic cases, determined the final diagnosis, and displayed them into clinical vignettes. Physicians typed the determined text with the clinical vignettes in the ChatGPT-3.5 and ChatGPT-4 prompts to generate the top 10 differential diagnoses. The ChatGPT models were not specially trained or further reinforced for this task. Three GIM physicians from other medical institutions created differential diagnosis lists by reading the same clinical vignettes. We measured the rate of correct diagnosis within the top 10 differential diagnosis lists, top 5 differential diagnosis lists, and the top diagnosis. RESULTS: In total, 52 case reports were analyzed. The rates of correct diagnosis by ChatGPT-4 within the top 10 differential diagnosis lists, top 5 differential diagnosis lists, and top diagnosis were 83% (43/52), 81% (42/52), and 60% (31/52), respectively. The rates of correct diagnosis by ChatGPT-3.5 within the top 10 differential diagnosis lists, top 5 differential diagnosis lists, and top diagnosis were 73% (38/52), 65% (34/52), and 42% (22/52), respectively. The rates of correct diagnosis by ChatGPT-4 were comparable to those by physicians within the top 10 (43/52, 83% vs 39/52, 75%, respectively; P=.47) and within the top 5 (42/52, 81% vs 35/52, 67%, respectively; P=.18) differential diagnosis lists and top diagnosis (31/52, 60% vs 26/52, 50%, respectively; P=.43) although the difference was not significant. The ChatGPT models' diagnostic accuracy did not significantly vary based on open access status or the publication date (before 2011 vs 2022). CONCLUSIONS: This study demonstrates the potential diagnostic accuracy of differential diagnosis lists generated using ChatGPT-3.5 and ChatGPT-4 for complex clinical vignettes from case reports published by the GIM department. The rate of correct diagnoses within the top 10 and top 5 differential diagnosis lists generated by ChatGPT-4 exceeds 80%. Although derived from a limited data set of case reports from a single department, our findings highlight the potential utility of ChatGPT-4 as a supplementary tool for physicians, particularly for those affiliated with the GIM department. Further investigations should explore the diagnostic accuracy of ChatGPT by using distinct case materials beyond its training data. Such efforts will provide a comprehensive insight into the role of artificial intelligence in enhancing clinical decision-making.

DOI： 10.2196/48808

Phase-dependent trends of male hypogonadism in long COVID patients. Reviewed

Naruhiko Sunada, Yuki Otsuka, Hiroyuki Honda, Kazuki Tokumasu, Fumio Otsuka

Endocrine journal 70 ( 7 ) 755 - 756 2023.7

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

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

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

Examination on education in AGHD (Adult Growth Hormone Deficiency) for medical staff Reviewed

越智可奈子, 徳増一樹, 大塚勇輝, 中野靖浩, 小比賀美香子, 大塚文男

医学教育 54 ( Suppl. ) 296 - 296 2023.7

Acute arthritis caused by sarcoidosis. Reviewed

Rio Ogami, Yuki Otsuka, Kou Hasegawa, Kazuki Tokumasu, Mikako Obika, Masanori Fujii, Fumio Otsuka

Journal of general and family medicine 24 ( 4 ) 264 - 265 2023.7

Language：English

Here we report a case of sarcoidosis which demonstrated with bilateral ankle arthritis. We usually do not consider sarcoidosis routinely for the differential diagnosis of acute arthritis, however, up to 15 to 25% of sarcoidosis complicate arthritis, typically in ankle joints. Sarcoid arthritis is reported to occur mainly in young northern Europe women, whereas this case intimate that we should take sarcoidosis into account as the differential diagnosis of ankle arthralgia also among Asian men especially when combining upper respiratory symptoms.

DOI： 10.1002/jgf2.621

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

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

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

Symptomatic Characteristics of Hypozincemia Detected in Long COVID Patients. Reviewed International journal

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

Journal of clinical medicine 12 ( 5 ) 2023.3

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

OBJECTIVES: The aim of this study was to determine the characteristics of hypozincemia in long COVID patients. METHODS: This study was a single-center retrospective observational study for outpatients who visited the long COVID clinic established in a university hospital during the period from 15 February 2021 to 28 February 2022. Characteristics of patients with a serum zinc concentration lower than 70 μg/dL (10.7 μmol/L) were compared with characteristics of patients with normozincemia. RESULTS: In a total of 194 patients with long COVID after excluding 32 patients, hypozincemia was detected in 43 patients (22.2%) including 16 male patients (37.2%) and 27 female patients (62.8%). Among various parameters including the background characteristics of the patients and medical histories, the patients with hypozincemia were significantly older than the patients with normozincemia (median age: 50 vs. 39 years). A significant negative correlation was found between serum zinc concentrations and age in male patients (R = -0.39; p < 0.01) but not in female patients. In addition, there was no significant correlation between serum zinc levels and inflammatory markers. General fatigue was the most frequent symptom in both male patients with hypozincemia (9 out of 16: 56.3%) and female patients with hypozincemia (8 out of 27: 29.6%). Patients with severe hypozincemia (serum zinc level lower than 60 μg/dL) had major complaints of dysosmia and dysgeusia, which were more frequent complaints than general fatigue. CONCLUSIONS: The most frequent symptom in long COVID patients with hypozincemia was general fatigue. Serum zinc levels should be measured in long COVID patients with general fatigue, particularly in male patients.

DOI： 10.3390/jcm12052062

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

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

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

Differences in Stress Perception of Medical Students Depending on In-Person Communication and Online Communication during the COVID-19 Pandemic: A Japanese Cross-Sectional Survey. Reviewed International journal

Kazuki Tokumasu, Yoshito Nishimura, Yoko Sakamoto, Mikako Obika, Hitomi Kataoka, Fumio Otsuka

International journal of environmental research and public health 20 ( 2 ) 2023.1

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

BACKGROUND: Excessive psychological stress in medical students affects their mental health and causes problems such as burnout and depression. Furthermore, changes in the learning environment to online learning due to the COVID-19 pandemic have had a psychological effect on medical students. However, the relationships between medical students' perceived stress and different methods of communication, including in-person and online communication, remain unclear. The purpose of this study was to investigate the differences in stress perception of medical students depending on in-person communication and online communication during the COVID-19 pandemic. METHODS: This study was a cross-sectional study conducted from September to October in 2020. All of the students of Okayama University School of Medicine were asked to participate in a questionnaire survey. The explanatory variables were the frequency and length of communications with others (by in-person or online communication), empathy, and lifestyle. The main outcome measure was perceived stress. Subgroup analysis was conducted for students who preferred to be by themselves and students who preferred to study together and interact with other people. Univariate analysis and multivariate multiple regression analysis were conducted. Gender and grade, which have been shown to be associated with stress in previous studies, were used as covariates for multiple regression analysis. RESULTS: Valid responses to the questionnaire survey were received from 211 (29.4%) of the 717 students. There was no significant association between perceived stress and online communication, but the number of people with which students had in-person communication (1-2 people compared to 0 as a control, regression coefficient [B] = -4.4, 95% confidence interval [CI]; -7.8, -1.1, more than 10 people, B = -12, 95% CI: -18, -5.8) and the length of communication (more than 120 min, B = -4.5, 95% CI: -8.1, -0.92) were associated with a reduction in perceived stress. In subgroup analysis, the number of people with in-person communication and the length of communication had significant associations with stress reduction even in the group of students who had a preference for being by themselves. CONCLUSION: In-person communications rather than online communications were associated with a lower level of perceived stress. In subgroup analysis, this trend was statistically significant in the group of students who had a preference for being by themselves.

DOI： 10.3390/ijerph20021579

[Report: Symposium "Fostering the Power to Open Up the Future and Collaboration among Academic Societies in the Field of Social Medicine: How to Promote and Support the Activities of Young Scientists"]. Reviewed

Hatasu Kobayashi, Mako Nagayoshi, Satoru Kanamori, Kazuki Tokumasu, Takayo Nakabe, Keisuke Kuwahara

Nihon eiseigaku zasshi. Japanese journal of hygiene 78 2023

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

The recruitment and training of early-career researchers are important for the development of science, especially in countries with low birth rates, such as Japan. In several academic societies for social medicine, early-career researchers have formed associations for the purposes of networking and career development. However, to date, little information about the activities of these associations has been shared. Therefore, we organized a symposium at the 93rd Annual Meeting of the Japanese Society for Hygiene (March 4, 2023) to introduce the early-career researcher associations that have been formed within five academic societies namely the Japanese Society for Hygiene, Japan Epidemiological Association, Japan Society for Occupational Health, Japan Society for Medical Education, and Japan Society for Healthcare Administration. In this paper, we summarize the activities, challenges, and future prospects of each association and their strategies for future development and collaboration on the basis of presentations and discussions at the symposium.

DOI： 10.1265/jjh.23005

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

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

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

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

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

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 < 0.01), dysgeusia (14% vs. 40%, ** p < 0.01) and hair loss (7% vs. 28%, ** p < 0.01) but had higher frequencies of fatigue (65% vs. 50%, * p < 0.05), insomnia (26% vs. 13%, * p < 0.05) and cough (20% vs. 7%, ** p < 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

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 58 ( 7 ) 850 - 850 2022.6

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：{MDPI} {AG}

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

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

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

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

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

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

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

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

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

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

Relationship between patients' characteristics and efficacy of calcimimetics for primary hyperparathyroidism in the elderly. Reviewed International journal

Koichiro Yamamoto, Yasuhiro Nakano, Kazuki Tokumasu, Hiroyuki Honda, Kou Hasegawa, Asuka Sato, Hiroko Ogawa, Mikako Obika, Yoshihisa Hanayama, Fumio Otsuka

Clinical case reports 10 ( 4 ) e05713 2022.4

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

Calcimimetic treatment has been reported to be effective for primary hyperparathyroidism (PHPT). Nine elderly PHPT patients who had been treated with calcimimetics were retrospectively analyzed. It was found that calcimimetics can reduce elevated serum calcium levels in elderly PHPT patients with low femoral DEXA %YAM and low urinary cAMP levels.

DOI： 10.1002/ccr3.5713

The Power of Peer Learning-An Attempt of Collaborative Construction and Management of Online Journal Club with Physicians of the Same Generation- Reviewed

橋本忠幸, 小杉俊介, 金澤剛志, 金澤剛志, 徳増一樹, 木戸敏喜

医学教育 53 ( 2 ) 157 - 162 2022.4

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

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

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 < 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

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

Language：Japanese Publisher：(一社)日本感染症学会

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。

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J00276&link_issn=&doc_id=20220406400006&doc_link_id=1390010292792199424&url=https%3A%2F%2Fcir.nii.ac.jp%2Fcrid%2F1390010292792199424&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_3.gif

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

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

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

Recovery From Alopecia After COVID-19. Reviewed International journal

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

Cureus 14 ( 1 ) e21160 2022.1

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

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

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

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

PloS one 17 ( 4 ) e0267587 2022

Language：English Publishing type：Research paper (scientific journal) Publisher：PUBLIC LIBRARY SCIENCE

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

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

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

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

Kazuki Tokumasu, Kanako Ochi, Fumio Otsuka

BMJ case reports 14 ( 10 ) 2021.10

Authorship：Lead author 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

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

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

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

Y ObjectivesVitamin 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.MethodsWe 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.ResultsThe 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) x 10(-3)] versus elderly females (aged >= 50 years) [7.9 (3.3-10.1) x 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).ConclusionsThe 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

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

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

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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

Isolated adrenocorticotropin deficiency induced by pembrolizumab for hypopharyngeal cancer: A case report. Reviewed International journal

Koichiro Yamamoto, Kazuki Tokumasu, Kosuke Oka, Kou Hasegawa, Fumio Otsuka

Clinical case reports 9 ( 6 ) e04305 2021.6

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

We report a case of isolated adrenocorticotropin deficiency caused by pembrolizumab. This condition can be fatal, but its rarity causes under-recognition. Oncologists should pay attention to adrenal insufficiency due to pembrolizumab.

DOI： 10.1002/ccr3.4305

Clinical Utility of the Ratio of Urinary Free Cortisol to Aldosterone as an Index for Inflammatory and Metabolic Dysregulation Reviewed International journal

Yuki Otsuka, Yasuhiro Nakano, Kazuki Tokumasu, Hiroyuki Honda, Mikako Obika, Kou Hasegawa, Yoshihisa Hanayama, Koichi Itoshima, Fumio Otsuka

ANNALS OF CLINICAL AND LABORATORY SCIENCE 51 ( 3 ) 352 - 358 2021.5

Language：English Publishing type：Research paper (scientific journal) Publisher：ASSOC CLINICAL SCIENTISTS

Objective. Urinary free cortisol (UFC) is a reliable marker to avoid cortisol fluctuation and the effects of binding proteins. However, UFC levels are affected by fluid intake and urine volume, and the normal levels range widely. Methods. To discover the utility of the ratio of urinary cortisol to aldosterone excretions, 246 patients in whom daily excretions of UFC and aldosterone (UAC) were measured were retrospectively analyzed. Results. The UFC/UAC ratio showed significant positive and negative correlations with the levels of serum cortisol (R=0.287) and aldosterone (R=-0.762), respectively. The UFC/UAC ratio increased with aging in female patients, while it was not altered by the level of BMI in either gender. Markers for metabolic and inflammatory status, including hemoglobin A1c (R=0.327), albumin (R=-0.331), C-reactive protein (R=0.317), ferritin (R=0.473), and D-dimer (R=0.569), showed correlations with the ratio of UFC/UAC that were more significant than the correlations with the serum level of cortisol or UFC alone. Of note, the UFC/UAC ratio was shown to be an indicator for the risk of diabetes (AUC: 0.765), hypoalbuminemia (0.839), hyper-CRPemia (0.748), and thrombophilia (0.824), in which the cut-off levels of the UFC/UAC ratio were around 12. Conclusion. The UFC/UAC ratio is a variable for detecting metabolic and inflammatory complications related to adrenocortical dysfunction.

Droopy eyelid due to IgG4-related dacryoadenitis Reviewed 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

Endogenous Bacterial Endophthalmitis Caused by Iliopsoas Abscess Reviewed

Weiying Sun, Yusuke Shiode, Kazuki Tokumasu, Shuhei Kimura, Mio Hosokawa, Shinichiro Doi, Kosuke Takahashi, Ryo Matoba, Fumio Otsuka, Yuki Morizane

ACTA MEDICA OKAYAMA 75 ( 2 ) 249 - 253 2021.4

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

A 79-year-old woman presented to our hospital with a 10-day history of gradually worsening binocular vision and severe backache. Further investigations revealed poor bilateral best-corrected visual acuities (BCVA), bilateral vitreous opacities, gray-white lesions scattered throughout the retina, and a left iliopsoas abscess on CT that later grew out methicillin-sensitive S. aureus. The abscess was drained and intravenous antibiotics were initiated, but the left eye additionally required intravitreal vancomycin. BCVA for both eyes normalized within 1 year. Intramuscular abscess should be considered as a possible primary lesion in cases of endogenous bacterial endophthalmitis.

DOI： 10.18926/AMO/61909

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

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

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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

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

Language：English Publishing type：Research paper (scientific journal) Publisher：JMIR PUBLICATIONS, INC

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

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

Hideharu Hagiya, Kazuki Tokumasu, Mikako Obika, Fumio Otsuka

Postgraduate medical journal 98 ( e3 ) e183-e184 2021.1

Without a silhouette Reviewed International journal

Yosuke Sazumi, Kazuki Tokumasu, Hideharu Hagiya, Fumio Otsuka

CLINICAL CASE REPORTS 9 ( 1 ) 574 - 575 2021.1

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

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

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

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

Language：English Publishing type：Research paper (scientific journal) Publisher：OKAYAMA UNIV MED SCHOOL

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

Antibiotic literacy among Japanese medical students Reviewed International journal

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

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

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

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

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

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

【パンデミック下の医学教育-現在進行形の実践報告-】卒後教育 COVID-19パンデミック下における初期研修医教育 Reviewed

橋本忠幸, 小杉俊介, 徳増一樹

医学教育 51 ( 3 ) 320 - 322 2020.6

Calciphylaxis of the fingers Reviewed

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

JOURNAL OF GENERAL AND FAMILY MEDICINE 21 ( 2 ) 25 - 26 2020.3

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

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

Myxedema coma accompanied by sick sinus syndrome and hypoventilation: A case report Reviewed

Ko Harada, Shuntaro Murakami, Kazuki Tokumasu, Yu Togawa, Fumio Otsuka

JOURNAL OF GENERAL AND FAMILY MEDICINE 20 ( 5 ) 206 - 208 2019.9

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

Myxedema coma is an emergency presentation of hypothyroidism, and cardiopulmonary manifestations of the disease are related to a high mortality rate. We herein report a case of myxedema coma accompanied by sick sinus syndrome requiring temporary cardiac pacing and hypercapnic respiratory failure in an 87-year-old woman. This case is unique because both of the cardiac and pulmonary manifestations were reversible and successfully treated with thyroid hormone replacement. Our case indicates that early detection of the condition and administration of levothyroxine are essential to improve the life-threatening condition and avoid invasive treatment such as permanent pacemaker implantation or intubation.

DOI： 10.1002/jgf2.267

初期研修後の勤務先はどのようにして決めましたか?(研修4ヵ月) Invited

徳増一樹

岡山医学会雑誌 131 ( 1 ) 46 - 46 2019.4

インフルエンザウイルス感染後に二次性肺炎でMSSA菌血症に至った1例 Reviewed

白壁勝大, 永田恵蔵, 板野雄基, 徳増一樹

沖縄医学会雑誌 56 ( 4 ) 22 - 24 2018

Language：Japanese Publisher：沖縄県医師会医学会

78歳女性。インフルエンザB型感染後、一旦は解熱したが、再度40℃の発熱を認め、湿性咳嗽や喀痰の増加、頻呼吸が出現したため当院へ救急外来となった。受診時、検査および胸部X線・CT、喀痰グラム染色より、インフルエンザウイルス感染に合併した黄色ブドウ球菌性肺炎と診断され、入院の上、バンコマイシン、セファゾリンの投与を開始した。入院2日目にMSSA菌血症が確認され、4日目に感受性の結果からバンコマイシンを中止し、その後は解熱し、徐々に呼吸状態の安定を認め、血液培養も陰性化し、抗菌薬は合計28日間使用し終了した。

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