Faculty Profiles - OTSUKA Fumio

Hypothalamic Mass Detected in Langerhans Cell Histiocytosis.

Ryosuke Takase, Yasuhiro Nakano, Shin Morizane, Fumio Otsuka

Internal medicine (Tokyo, Japan) 60 ( 11 ) 1795 - 1795 2021.6

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

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

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

Acta medica Okayama 75 ( 3 ) 299 - 306 2021.6

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

Orbital mass and hairy kidney as characteristics of Erdheim-Chester disease. International journal

Koichiro Yamamoto, Kosuke Oka, Kou Hasegawa, Fumio Otsuka

Clinical case reports 9 ( 6 ) e04333 2021.6

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

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis, involving multiple organs. We report a case of ECD with typical features of an orbital mass and "hairy kidneys," whose recognition can lead to early diagnosis and treatment.

DOI： 10.1002/ccr3.4333

Leucine-rich alpha-2 glycoprotein as a marker of mucosal healing in inflammatory bowel disease. International journal

Eriko Yasutomi, Toshihiro Inokuchi, Sakiko Hiraoka, Kensuke Takei, Shoko Igawa, Shumpei Yamamoto, Masayasu Ohmori, Shohei Oka, Yasushi Yamasaki, Hideaki Kinugasa, Masahiro Takahara, Keita Harada, Masaki Furukawa, Kouichi Itoshima, Ken Okada, Fumio Otsuka, Takehiro Tanaka, Toshiharu Mitsuhashi, Jun Kato, Hiroyuki Okada

Scientific reports 11 ( 1 ) 11086 - 11086 2021.5

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

Leucine-rich alpha-2 glycoprotein (LRG) may be a novel serum biomarker for patients with inflammatory bowel disease. The association of LRG with the endoscopic activity and predictability of mucosal healing (MH) was determined and compared with those of C-reactive protein (CRP) and fecal markers (fecal immunochemical test [FIT] and fecal calprotectin [Fcal]) in 166 ulcerative colitis (UC) and 56 Crohn's disease (CD) patients. In UC, LRG was correlated with the endoscopic activity and could predict MH, but the performance was not superior to that of fecal markers (areas under the curve [AUCs] for predicting MH: LRG: 0.61, CRP: 0.59, FIT: 0.75, and Fcal: 0.72). In CD, the performance of LRG was equivalent to that of CRP and Fcal (AUCs for predicting MH: LRG: 0.82, CRP: 0.82, FIT: 0.70, and Fcal: 0.88). LRG was able to discriminate patients with MH from those with endoscopic activity among UC and CD patients with normal CRP levels. LRG was associated with endoscopic activity and could predict MH in both UC and CD patients. It may be particularly useful in CD.

DOI： 10.1038/s41598-021-90441-x

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

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

Acta medica Okayama 75 ( 5 ) 567 - 574 2021.5

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

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

DOI： 10.18926/AMO/62769

Droopy eyelid due to IgG4-related dacryoadenitis. International journal

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

Postgraduate medical journal 97 ( 1147 ) 333 - 334 2021.5

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

Pseudoacromegaly with acromegalic features in radiography. International journal

Koichiro Yamamoto, Kosuke Oka, Hiroyuki Honda, Kou Hasegawa, Fumio Otsuka

Clinical case reports 9 ( 5 ) e04095 2021.5

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

Pseudoacromegaly is a condition characterized by acromegalic physical features without growth hormone excess, for which radiographic observation has seldom been reported. This is a rare case of pseudoacromegaly.

DOI： 10.1002/ccr3.4095

HIV-associated cerebral lymphoma in an elderly patient.

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

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

どのように臨床研修医のモチベーションは上がるのか? プライマリ・ケア主体的診療の重要性

徳増一樹, 小比賀美香子, 尾原晴雄, 菊川誠, 大塚文男

日本プライマリ・ケア連合学会学術大会 12回 np637 - np637 2021.5

周期的発熱、及び腹痛精査中に診断された正中弓状靱帯圧迫症候群の1例

乃美優孝, 井口俊博, 青山祐樹, 竹井健介, 安富絵里子, 井川翔子, 大森正泰, 岡昌平, 竹内桂子, 山崎泰史, 衣笠秀明, 原田馨太, 平岡佐規子, 岡田裕之, 徳増一樹, 大塚文男, 矢野修也, 菊地覚次, 坂本真樹

日本消化器病学会中国支部例会プログラム・抄録集 115回 83 - 83 2021.5

Orexin A Enhances Pro-Opiomelanocortin Transcription Regulated by BMP-4 in Mouse Corticotrope AtT20 Cells. International journal

Satoshi Fujisawa, Motoshi Komatsubara, Naoko Tsukamoto-Yamauchi, Nahoko Iwata, Takahiro Nada, Jun Wada, Fumio Otsuka

International journal of molecular sciences 22 ( 9 ) 2021.4

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

Orexin is expressed mainly in the hypothalamus and is known to activate the hypothalamic-pituitary-adrenal (HPA) axis that is involved in various stress responses and its resilience. However, the effects of orexin on the endocrine function of pituitary corticotrope cells remain unclear. In this study, we investigated the roles of orexin A in pro-opiomelanocortin (POMC) transcription using mouse corticotrope AtT20 cells, focusing on the bone morphogenetic protein (BMP) system expressed in the pituitary. Regarding the receptors for orexin, type 2 (OXR2) rather than type 1 (OX1R) receptor mRNA was predominantly expressed in AtT20 cells. It was found that orexin A treatment enhanced POMC expression, induced by corticotropin-releasing hormone (CRH) stimulation through upregulation of CRH receptor type-1 (CRHR1). Orexin A had no direct effect on the POMC transcription suppressed by BMP-4 treatment, whereas it suppressed Smad1/5/9 phosphorylation and Id-1 mRNA expression induced by BMP-4. It was further revealed that orexin A had no significant effect on the expression levels of type I and II BMP receptors but upregulated inhibitory Smad6/7 mRNA and protein levels in AtT20 cells. The results demonstrated that orexin A upregulated CRHR signaling and downregulated BMP-Smad signaling, leading to an enhancement of POMC transcription by corticotrope cells.

DOI： 10.3390/ijms22094553

Dysphagia Induced by Acromegalic Arthropathy.

Manami Fujita, Yasuhiro Nakano, Hiroyuki Sakae, Fumio Otsuka

Internal medicine (Tokyo, Japan) 60 ( 7 ) 1127 - 1128 2021.4

An adrenal incidentaloma caused by synchronous and isolated metastasis. International journal

Koichiro Yamamoto, Kosuke Oka, Hiroyuki Honda, Kou Hasegawa, Yoshihisa Hanayama, Tomofumi Watanabe, Yusuke Tominaga, Atsushi Takamoto, Takayuki Hara, Fumio Otsuka

Clinical case reports 9 ( 4 ) 2494 - 2495 2021.4

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

We report a patient with adrenal incidentaloma due to synchronous and isolated metastasis from lung cancer, which is a relatively rare condition. Close checkups for incidentaloma in oncologic patients are mandatory, leading to successful operation.

DOI： 10.1002/ccr3.3996

Endogenous Bacterial Endophthalmitis Caused by Iliopsoas Abscess.

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

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

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

Scientific reports 11 ( 1 ) 7246 - 7246 2021.3

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

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

DOI： 10.1038/s41598-021-86431-8