研究者詳細 - 大西　浩文

論文 - 大西　浩文

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Prevalence of and risk factors for enlarged perivascular spaces in adult patients with moyamoya disease

Tomoyoshi Kuribara, Takeshi Mikami, Katsuya Komatsu, Hime Suzuki, Hirofumi Ohnishi, Kiyohiro Houkin, Nobuhiro Mikuni

BMC NEUROLOGY ( BIOMED CENTRAL LTD ) 17 ( 1 ) 149 2017年08月 [査読有り]

Background: Enlarged perivascular spaces (EPVS) are often observed with magnetic resonance imaging in patients with small vessel disease. However, the risk factors, radiological features, and clinical relevance of EPVS in patients with moyamoya disease are poorly understood. The purpose of this study was to evaluate EPVS, the risk factors of many EPVS, and the pathophysiology of EPVS in adult patients with moyamoya disease. Methods: One hundred cerebral hemispheres of 50 adult patients with moyamoya disease were examined. The control group consisted of 50 age/sex-matched patients without ischemic disease. The numbers of EPVS at the level of the centrum semiovale per hemisphere were compared between the moyamoya disease and control groups. In each hemisphere, the total numbers of EPVS were categorized into five grades (0-4), and the clinical and radiological characteristics of the predictive factors in patients in the high EPVS grade group (EPVS grade = 4) were assessed. Results: The EPVS counts and grades were significantly higher in the moyamoya disease group. Analyses of the background characteristics of the patients with moyamoya disease revealed that significantly higher prevalence of high EPVS grades were associated with the female sex, hypertension, high magnetic resonance angiography scores, high numbers of flow voids in the basal ganglia, high brain atrophy scores, ivy signs, and white matter lesions. A logistic multivariate analysis of the patients with high EPVS grades revealed significant associations with the female sex, hypertension, and flow voids in the basal ganglia. Conclusions: Increased EPVS were confirmed in adult patients with moyamoya disease, and the associated clinical and radiological factors were identified. The presence of hypertension, the female sex, and flow voids in the basal ganglia were important for predicting high EPVS grades in patients with moyamoya disease. Reductions in arterial pulsations with steno-occlusive changes can inhibit the flow of interstitial fluid, which can increase the number of EPVS in patients with moyamoya disease. Other clinical factors, such as the female sex and hypertension, may promote secondary brain damage in patients with moyamoya disease. Further evaluations of EPVS in patients with moyamoya disease are needed to better understand their pathophysiological importance.

Pathophysiological consideration of medullary streaks on FLAIR imaging in pediatric moyamoya disease

Hime Suzuki, Takeshi Mikami, Tomoyoshi Kuribara, Kazuhisa Yoshifuji, Katsuya Komatsu, Yukinori Akiyama, Hirofumi Ohnishi, Kiyohiro Houkin, Nobuhiro Mikuni

JOURNAL OF NEUROSURGERY-PEDIATRICS ( AMER ASSOC NEUROLOGICAL SURGEONS ) 19 ( 5 ) 560 - 566 2017年05月 [査読有り]

OBJECTIVE Medullary streaks detected on fluid-attenuated inversion recovery (FLAIR) imaging have been considered to be reflected ischemic regions in pediatric moyamoya disease. The purpose of this study was to evaluate these medullary streaks both clinically and radiologically and to discuss associated pathophysiological concerns. METHODS The authors retrospectively reviewed data from 14 consecutive pediatric patients with moyamoya disease treated between April 2009 and June 2016. Clinical and radiological features and postoperative imaging changes were analyzed. In 4 patients, hyperintense medullary streaks on FLAIR imaging (HMSF) at the level of the centrum semiovale were detected. RESULTS The HMSF were coincident with hyperintense medullary streaks on a T2-weighted image, though they were not completely coincident with the vasculature on either a T2*-weighted image or contrast-enhanced CT. Analysis revealed significantly higher values in terms of MR angiography scores, number of flow voids of the basal ganglia, and the presence of the medullary artery in the group with HMSF than in those without. In contrast, the presence of white matter damage was significantly less frequent in the HMSF group. All HMSF disappeared after surgery, and the mean apparent diffusion coefficient at the same level was significantly reduced postoperatively. CONCLUSIONS Although HMSF should be associated with collateral circulation in moyamoya disease, other factors may be involved, including stagnated cerebrospinal fluid or vasogenic edema that is relevant to the impaired state of the white matter. Findings in this study provide insight into the pathophysiological basis of the perivascular space in moyamoya disease.

Soleal vein dilatation assessed by ultrasonography is an independent predictor for deep vein thrombosis after major orthopedic surgery

Kiyoshi Abe, Satoshi Yuda, Kenji Yasui, Ayumi Okubo, Chihiro Kobayashi, Atsuko Muranaka, Hirofumi Ohnishi, Akiyoshi Hashimoto, Atsushi Teramoto, Satoshi Nagoya, Kazufumi Tsuchihashi, Toshihiko Yamashita, Satoshi Takahashi, Tetsuji Miura

JOURNAL OF CARDIOLOGY ( ELSEVIER SCIENCE BV ) 69 ( 5-6 ) 756 - 762 2017年05月 [査読有り]

Background: Deep vein thrombosis (DVT) develops after major orthopedic surgery despite the current use of prophylaxis. DVT frequently develops in the soleal vein (SV) and might develop easily at the site of SV dilatation because of blood flow stasis. However, whether preoperative SV dilatation detected by ultrasonography predicts DVT after major orthopedic surgery remains unknown. Objective: We examined whether SV dilatation detected by preoperative ultrasonography predicts DVT after major orthopedic surgery. Methods: Ultrasonography was performed preoperatively and postoperatively in 243 patients with orthopedic diseases (mean age of 67 +/- 13 years, 77% women) who underwent total hip arthroplasty (THA, n = 180) or total knee arthroplasty (TKA, n = 63). Presence of DVT was diagnosed by ultrasonography and SV diameter >= 10 mm was defined as SV dilatation. Patients with preoperative DVT were excluded. Results: Sixty-nine patients (28%) developed postoperative DVT. SV dilatation was found in 24 patients (10%), and 16 (67%) of those patients had postoperative DVT. Multivariate logistic regression analysis showed that female gender [odds ratio (OR): 4.09, p = 0.004], TKA (OR: 2.52, p = 0.011), and SV dilatation (OR: 6.67, p < 0.001), but not presence of comorbidities, medications, or plasma D-dimer value, independently predict postoperative DVT. Subgroup analyses according to the operation site showed that female gender (OR: 3.27, p = 0.043) and SV dilatation (OR: 3.72, p = 0.022) were independent predictors of postoperative DVT in the THA group. SV dilatation (OR: 12.0, p = 0.027) was an independent predictor of postoperative DVT also in the TKA group. Conclusions: In addition to gender and TKA, SV dilatation detected by ultrasonography is an independent predictor of DVT after major orthopedic surgery. Determination of SV diameter by ultrasonography before major orthopedic surgery is useful for assessing the risk of postoperative DVT. (C) 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Factors affecting survival of patients in the acute phase of upper cervical spine injuries

Tomonori Morita, Tsuneo Takebayashi, Hideto Irifune, Hirofumi Ohnishi, Suguru Hirayama, Toshihiko Yamashita

ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY ( SPRINGER ) 137 ( 4 ) 543 - 548 2017年04月 [査読有り]

Introduction In recent years, on the one hand, the mortality rates of upper cervical spine injuries, such as odontoid fractures, were suggested to be not so high, but on the other hand reported to be significantly high. Furthermore, it has not been well documented the relationship between survival rates and various clinical features in those patients during the acute phase of injury because of few reports. This study aimed to evaluate survival rates and acute-phase clinical features of upper cervical spine injuries. Methods We conducted a retrospective review of all patients who were transported to the advanced emergency medical center and underwent computed tomography of the cervical spine at our hospital between January 2006 and December 2015. We excluded the patients who were discovered in a state of cardiopulmonary arrest (CPA) and could not be resuscitated after transportation. Of the 215 consecutive patients with cervical spine injuries, we examined 40 patients (18.6%) diagnosed with upper cervical spine injury (males, 28; females, 12; median age, 58.5 years). Age, sex, mechanism of injury, degree of paralysis, the level of cervical injury, injury severity score (ISS), and incidence of CPA at discovery were evaluated and compared among patients classified into the survival and mortality groups. Results The survival rate was 77.5% (31/40 patients). In addition, complete paralysis was observed in 32.5% of patients. The median of ISS was 34.0 points, and 14 patients (35.0%) presented with CPA at discovery. Age, the proportion of patients with complete paralysis, a high ISS, and incidence of CPA at discovery were significantly higher in the mortality group (p = 0.038, p = 0.038, p < 0.001, and p < 0.001, respectively). Conclusions Elderly people were more likely to experience upper cervical spine injuries, and their mortality rate was significantly higher than that in injured younger people. In addition, complete paralysis, high ISS, a state of CPA at discovery, was significantly higher in the mortality group.

Volatile Organic Compounds in Exhaled Breath of Idiopathic Pulmonary Fibrosis for Discrimination from Healthy Subjects

Yu-ichi Yamada, Gen Yamada, Mitsuo Otsuka, Hirotaka Nishikiori, Kimiyuki Ikeda, Yasuaki Umeda, Hirofumi Ohnishi, Koji Kuronuma, Hirofumi Chiba, Joerg Ingo Baumbach, Hiroki Takahashi

LUNG ( SPRINGER ) 195 ( 2 ) 247 - 254 2017年04月 [査読有り]

Purpose Human breath analysis is proposed with increasing frequency as a useful tool in clinical application. We performed this study to find the characteristic volatile organic compounds (VOCs) in the exhaled breath of patients with idiopathic pulmonary fibrosis (IPF) for discrimination from healthy subjects. Methods VOCs in the exhaled breath of 40 IPF patients and 55 healthy controls were measured using a multi-capillary column and ion mobility spectrometer. The patients were examined by pulmonary function tests, blood gas analysis, and serum biomarkers of interstitial pneumonia. Results We detected 85 VOC peaks in the exhaled breath of IPF patients and controls. IPF patients showed 5 significant VOC peaks; p-cymene, acetoin, isoprene, ethylbenzene, and an unknown compound. The VOC peak of p-cymene was significantly lower (p < 0.001), while the VOC peaks of acetoin, isoprene, ethylbenzene, and the unknown compound were significantly higher (p < 0.001 for all) compared with the peaks of controls. Comparing VOC peaks with clinical parameters, negative correlations with VC (r =-0.393, p = 0.013), %VC (r =-0.569, p < 0.001), FVC (r = -0.440, p = 0.004), %FVC (r =-0.539, p < 0.001), DLco (r =-0.394, p = 0.018), and %DLco (r =-0.413, p = 0.008) and a positive correlation with KL-6 (r = 0.432, p = 0.005) were found for p-cymene. Conclusion We found characteristic 5 VOCs in the exhaled breath of IPF patients. Among them, the VOC peaks of p-cymene were related to the clinical parameters of IPF. These VOCs may be useful biomarkers of IPF.

非糖尿病かつ検尿異常のない場合もLDL-コレステロール120mg/dL以上はCKD-ステージG3への進展の危険因子となる

山下智久, 松本環, 大西浩文, 塙なぎさ, 田中希尚, 茂庭仁人, 古橋眞人, 三浦哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 ) 59 ( 3 ) 372 - 372 2017年04月

Co-expression of tissue factor and IL-6 in immature endothelial cells of cerebral cavernous malformations

Shouhei Noshiro, Takeshi Mikami, Yuko Kataoka-Sasaki, Masanori Sasaki, Hirofumi Ohnishi, Shunya Ohtaki, Masahiko Wanibuchi, Nobuhiro Mikuni, Jeffery D. Kocsis, Osamu Honmou

JOURNAL OF CLINICAL NEUROSCIENCE ( ELSEVIER SCI LTD ) 37 83 - 90 2017年03月 [査読有り]

Cerebral cavernous malformations (CCMs) are congenital abnormal clusters of capillaries that are prone to leaking and thought to result from a disorder of endothelial cells. The underlying pathology of CCM is not fully understood. We analyzed the expression of tissue factor (TF) and interleukin-6 (IL-6) in CCMs to determine the association of TF and IL-6 with clinical and pathological findings. Thirteen cases of operative specimens of sporadic CCMs were included in this study. The expression of messenger RNA of TF and IL-6 was assayed and the association with clinical factors was investigated. Then, the distribution of TF and IL-6 was examined with immunofluorescence. The mRNA expression of TF of CCMs was significantly higher than that of the control (p = 0.017), and was correlated with the number of hemorrhage appearances (p = 0.190, rho = 0.62). The mRNA expression level of IL-6 was significantly correlated with the mRNA expression level of TF (p = 0.034, rho = 0.58). Examination of immunostained sections indicated that TF+ cells were also positive for IL-6, and distributed around normal endothelial cells. Moreover, the TF+/1L-6(+) cells expressed CD31 and VEGFR2. The expressions of IL-6 and TF were correlated, and both were present in the same immature endothelial cells. TF is elevated in CCM and might mediate progressive events. These factors may play a prognostic role in CCM. (C) 2016 Elsevier Ltd. All rights reserved.

Pneumococcal vaccination reduces the risk of community-acquired pneumonia in children

Junko Hasegawa, Mitsuru Mori, Hirofumi Ohnishi, Takeshi Tsugawa, Tsukasa Hori, Yuko Yoto, Hiroyuki Tsutsumi

PEDIATRICS INTERNATIONAL ( WILEY ) 59 ( 3 ) 316 - 320 2017年03月 [査読有り]

Background: The seven-valent pneumococcal conjugate vaccine (PCV7) was introduced to Japan in 2009, after which there was a rapid decline in invasive pneumococcal disease. There are few data, however, on the effectiveness of PCV7 against community-acquired pneumonia (CAP). We conducted an ambispective cohort study among children aged 0-6 years old who attended day-care centers. Methods: A total of 624 children at 10 day-care centers in Sapporo, Japan participated in the study. The parents reported whether their child had received PCV7 one or more times, as well as the exact dates of vaccination from records in maternal and child health handbooks marked by pediatricians. Each CAP event was reported by parents according to doctor diagnosis. A Cox proportional hazards regression model was used to calculate the hazard ratio (HR) and 95% CI of CAP incidence reduced by PCV7 inoculation. Results: During the observational period, 94 subjects contracted CAP. After adjusting for potentially confounding variables, inoculation with PCV7 was significantly associated with a reduced risk of CAP (HR, 0.22; 95% CI: 0.130.34). On stratified analysis by age, PCV7 was significantly associated with a reduced risk of CAP in both children aged <3 years (HR, 0.31; 95% CI: 0.14-0.71), and those >= 3 years (HR, 0.20; 95% CI: 0.09-0.43). Conclusion: PCV7 is highly effective in reducing the risk of CAP in children attending day-care centers.

Serum FABP5 concentration is a potential biomarker for residual risk of atherosclerosis in relation to cholesterol efflux from macrophages

Masato Furuhashi, Masatsune Ogura, Megumi Matsumoto, Satoshi Yuda, Atsuko Muranaka, Mina Kawamukai, Akina Omori, Marenao Tanaka, Norihito Moniwa, Hirofumi Ohnishi, Shigeyuki Saitoh, Mariko Harada-Shiba, Kazuaki Shimamoto, Tetsuji Miura

SCIENTIFIC REPORTS ( NATURE PUBLISHING GROUP ) 7 ( 1 ) 217 2017年03月 [査読有り]

Cholesterol efflux capacity (CEC) from macrophages, the first step in the reverse cholesterol transport pathway, is inversely associated with residual risk for atherosclerotic cardiovascular disease. Fatty acid-binding protein 4 (FABP4) and FABP5 are expressed in both adipocytes and macrophages and play significant roles in the development of insulin resistance and atherosclerosis. Both FABP4 and FABP5 are secreted from cells, and their circulating levels are associated with insulin resistance and atherosclerosis. We investigated the association between CEC and levels of FABP4 and FABP5 in 250 subjects without any medications. CEC was positively correlated with HDL cholesterol level and negatively correlated with concentrations of high-sensitivity C-reactive protein (hsCRP) and FABP5, but not FABP4. Multiple regression analysis demonstrated that FABP5 concentration was an independent predictor of CEC after adjustment of age, gender and levels of HDL cholesterol and hsCRP. In 129 of the 250 subjects who underwent carotid ultrasonography, mean intima-media thickness was negatively correlated with CEC and was positively correlated with concentrations of FABP4 and FABP5. In conclusion, in contrast to FABP4, circulating FABP5 is associated with decreased CEC and carotid atherosclerosis, suggesting that FABP5 level is a regulatory factor of CEC and a potential biomarker for residual risk of atherosclerosis.

Role of dilatation and curettage performed for spontaneous or induced abortion in the etiology of endometrial thinning

Atsushi Azumaguchi, Hirofumi Henmi, Hirofumi Ohnishi, Toshiaki Endo, Tsuyoshi Saito

JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH ( WILEY ) 43 ( 3 ) 523 - 529 2017年03月 [査読有り]

AimThe aim of this study was to clarify the role of dilatation and curettage (D&C) performed for spontaneous or induced abortion in the etiology of endometrial thinning. MethodsThis was a retrospective and cross-sectional study of 310 infertile patients from January 2013 through December 2015. Endometrial thickness observed 5-7 days after ovulation in a natural menstrual cycle was correlated with the number of D&C noted in each patient's history. ResultsStudy 1 was an investigation of patients without D&C (group A: n = 232) and patients with D&C performed for spontaneous abortion (group B: n = 46). Study 2 was an investigation of patients in group A and patients with D&C performed for induced abortion (group C: n = 32). A significant negative correlation (P < 0.01) between endometrial thickness and number of D&C was observed in both studies. The mean endometrial thickness of the patients in group A was 10.9 2.1 mm. The mean endometrial thickness of the patients in group B with one and two D&C was 7.9 +/- 2.3 and 6.9 +/- 2.9 mm, respectively. The mean endometrial thickness of the patients in group C with one and two D&C was 9.1 +/- 2.3 and 7.8 +/- 2.0 mm, respectively. There was a tendency toward gradual endometrial thinning following repeated procedures and the number of previous D&C was significantly associated with endometrial thinning (P < 0.001) in both studies. ConclusionD&C performed for spontaneous or induced abortion may play a causal role in endometrial thinning.

A Multicenter Retrospective Study of Mogamulizumab Efficacy in Adult T-Cell Leukemia/Lymphoma

Satoshi Iyama, Tsutomu Sato, Hirofumi Ohnishi, Yuji Kanisawa, Shuichi Ohta, Takeshi Kondo, Akio Mori, Yutaka Tsutsumi, Hiroyuki Kuroda, Yasutaka Kakinoki, Satoshi Yamamoto, Tohru Takahashi, Motohiro Shindo, Yoshihiro Torimoto, Kazuya Sato, Hiroshi Iwasaki, Yoshihito Haseyama, Kyuhei Kohda, Yasuhiro Nagamachi, Yasuo Hirayama, Hajime Sakai, Yasuji Hirata, Takashi Fukuhara, Hiroshi Ikeda, Masayoshi Kobune, Junji Kato, Mitsutoshi Kurosawa

CLINICAL LYMPHOMA MYELOMA & LEUKEMIA ( CIG MEDIA GROUP, LP ) 17 ( 1 ) 23 - 30 2017年01月 [査読有り]

Mogamulizumab recently became available for the treatment of adult T-cell leukemia/lymphoma (ATL). We conducted a multicenter retrospective study of the efficacy of mogamulizumab for ATL treatment in patients in Japan and found that mogamulizumab is an effective therapeutic strategy in ATL. Some concern exists that the use of mogamulizumab in patients undergoing hematopoietic stem cell transplantation patients might cause severe graft-versus-host disease. Determining the optimum number of mogamulizumab administrations should be a priority for future studies. Background: Mogamulizumab, a defucosylated humanized monoclonal antibody targeting C-C chemokine receptor 4, recently became available for the treatment of adult T-cell leukemia/lymphoma (ATL). We conducted a multicenter retrospective study of the efficacy of mogamulizumab in ATL treatment in patients on Hokkaido Island, Japan. Materials and Methods: A total of 125 patients with ATL treated from January 2010 to December 2014 in 20 hospitals affiliated with the Hokkaido Hematology Study Group were enrolled in the present retrospective study. Results: Of the 125 ATL patients, 62 (46.6%) presented with the acute type, 51 (38.3%) with the lymphoma type, and 12 (9.0%) with the chronic type; the latter group included 7 unfavorable chronic cases. The median age at diagnosis was 68 years (range, 35-86 years). The median survival for those with acute, lymphoma, and unfavorable chronic types was 302, 279, and 921 days, respectively. Advanced age, high lactate dehydrogenase level, poor performance status (3-4), and the existence of B symptoms were unfavorable prognostic factors for overall survival (OS). Survival rate calculated from the day of diagnosis was significantly higher in patients treated with mogamulizumab. The OS of individuals receiving hematopoietic stem cell transplantation (HSCT) was superior to that of the non-HSCT group. The median interval between the last mogamulizumab dose and allogeneic HSCT was 38 days (range, 21-53 days). Of the 22 HSCT recipients who were not treated with mogamulizumab, overall acute graft-versus-host disease (aGVHD) and grade III-IV aGVHD occurred in 12 (54.5%) and 3 (13.6%) patients, respectively. However, overall aGVHD and grade III-IV aGVHD developed in 8 (88.9%) and 3 (33.3%) of the 9 HSCT recipients treated with mogamulizumab, respectively. Conclusion: Mogamulizumab improves OS in patients with ATL, although its use in HSCT patients might trigger severe GVHD. Determining the optimal pre-HSCT mogamulizumab treatment regimen is thus a priority. (C) 2016 Elsevier Inc. All rights reserved.

Distinct risk factors of atrial fibrillation in patients with and without coronary artery disease: A cross-sectional analysis of the BOREAS-CAG Registry data

Naoto Murakami, Masaya Tanno, Nobuaki Kokubu, Junichi Nishida, Nobutaka Nagano, Hirofumi Ohnishi, Hiroshi Akasaka, Takayuki Miki, Kazufumi Tsuchihashi, Tetsuji Miura

Open Heart ( BMJ Publishing Group ) 4 ( 1 ) e000573 2017年 [査読有り]

Objective: Although risk factors of atrial fibrillation (AF) in the general population have been characterised, their impacts on patients with specific diseases are unclear. Our aim was to determine whether risk factors of AF are different in patients with and those without coronary artery disease (CAD). Methods: We enrolled 1871 consecutive patients who underwent coronary angiography for evaluation of symptoms suggestive of CAD in the BOREAS-CAG Registry between August 2014 and January 2015. After exclusion of patients with valvular heart disease or a history of PCI/cardiac surgery, 1150 patients contributed to multivariate logistic regression analysis to identify risk factors of AF. We also retrieved data for 361 consecutive patients with CAD admitted to Sapporo Medical University Hospital between April 2013 and July 2014 and analysed data for 166 patients using the same inclusion and exclusion criteria as those in the BOREAS-CAG Registry. Results: Unexpectedly, CAD was independently associated with the absence of AF. The patients were then divided into a non-CAD group (n=576) and a CAD group (n=574) for further analysis. The brain natriuretic peptide level showed a strong association with AF regardless of the presence or absence of CAD. In the non-CAD group, lack of statin use was independently associated with AF, whereas high serum uric acid level was an independent explanatory variable of AF in the CAD group. The association of AF with uric acid was confirmed in a separate group of patients (n=166) enrolled in the CAD cohort in Sapporo Medical University Hospital. Conclusions: Major risk factors of AF are different in patients with CAD and those without CAD. Patients with CAD are more likely to develop AF when the serum uric acid level is high, whereas no statin administration predicts development of AF in patients without CAD.

Impact of the Number of Anti-Thrombosis Agents in Hemodialysis Patients: BOREAS-HD2 Study

Marenao Tanaka, Norihito Moniwa, Hirofumi Ohnishi, Tomohisa Yamashita, Masayuki Koyama, Yufu Gocho, Keitaro Nishizawa, Yukishige Kimura, Hirohito Sugawara, Sayaka Murakami, Yusuke Okazaki, Masato Furuhashi, Hideaki Yoshida, Tetsuji Miura

KIDNEY & BLOOD PRESSURE RESEARCH ( KARGER ) 42 ( 3 ) 553 - 564 2017年 [査読有り]

Background/Aims: Relationships between the number of anti-thrombosis agents, clinical benefits and adverse events in hemodialysis (HD) patients are unclear. Methods: All patients on HD in 22 institutes (n = 1,071) were enrolled and followed up for 3 years. After exclusion of patients with missing data, kidney transplantation or retraction of consent during the follow-up period (n = 204), mortality rate and ischemic and hemorrhagic events were compared between different regimens of anti-thrombosis agents. Results: The use of dual or triple antiplatelet (AP) agents (HR:2.03, 95% CI:1.01-4.13, p = 0.04) and the combination of an AP agent and warfarin (WF) (HR:4.84, 95% CI 1.96-11.96, p < 0.001) were associated with an increase in hemorrhagic events compared with no use of anti-thrombosis agents. No anti-thrombosis regimen was associated with a significant change in risk of ischemic stroke. The use of dual or triple AP agents, but not WF, was associated with an increase in cardiovascular mortality (HR:2.48, 95% CI:1.24-4.76, p = 0.01). Conclusion: A significant increase in hemorrhagic events by the use of dual or more AP agents and by co-administration of an AP agent and WF in patients on HD should be considered in planning their anti-thrombosis regimen. (C) 2017 The Author(s) Published by S. Karger AG, Basel

NIPPON DATAイベント判定委員会

大久保孝義, 門田文, 清原裕, 寶澤篤, 二宮利治, 中村幸志, 高嶋直敬, 宮本恵宏, 大澤正樹, 東山綾, 長澤晋哉, 久松隆史, 鳥居さゆ希, 八谷寛, 大西浩文, 櫻井勝, 浅山敬, 平田匠, 宮沢伊都子

厚生労働行政推進調査事業費補助金（循環器疾患・糖尿病等生活習慣病対策総合研究事業）社会的要因を含む生活習慣病リスク要因の解明を目指した国民代表集団の大規模コホート研究：NIPPON DATA80/90/2010 平成28年度総括・分担研究報告書（研究代表者三浦克之） - 21 - 24 2017年

The Serum Level of KL-6 Is Associated with the Risk of Insulin Resistance and New-onset Diabetes Mellitus: The Tanno-Sobetsu Study

Hiroshi Akasaka, Hirofumi Ohnishi, Yoshifumi Narita, Masami Kameda, Takayuki Miki, Hiroki Takahashi, Wari Yamamoto, Hitoshi Sohma, Naoya Masumori, Tetsuji Miura

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE ) 56 ( 22 ) 3009 - 3018 2017年 [査読有り]

Objective Inflammatory cytokines generated in visceral fat have been shown to contribute to the development of insulin resistance. The involvement of pulmonary inflammation in insulin resistance remains unclear, but smoking is known to be a risk factor for diabetes as well as chronic obstructive pulmonary disease. We herein examined the hypothesis that increased serum levels of lung interstitial injury biomarkers [surfactant protein (SP)-A, SP-D and Krebs von den Lungen (KL)-6] are associated with the risk of diabetes development. Methods For cross-sectional and longitudinal analyses, we enrolled 750 apparently healthy non-diabetic subjects who received annual examinations in 2011 or 2012 in the Tanno-Sobetsu cohort. Results A cross-sectional analysis showed that distinct clinical parameters were associated with SP-A, SP-D and KL-6. In a multiple regression analysis, independent explanatory variables were Brinkman index and brain natriuretic peptide (BNP) for SP-A, sex (women), BNP and body mass index (BMI) for SP-D, and age and BMI for KL-6. A longitudinal analysis of 415 subjects who received annual examinations in both 2011 and 2014 showed that 13 (3.1%) of the patients developed type 2 diabetes during the 3-year follow-up. A multiple logistic regression analysis showed the KL-6 levels, systolic blood pressure and homeostasis model assessment of insulin resistance (HOMA-IR) in 2011 to be independently associated with new-onset diabetes. In a multiple regression analysis for HOMA-IR in 2014, the KL-6 level and BMI in 2011 were selected as explanatory variables. Conclusion A modest elevation of the serum KL-6 level is therefore considered to be associated with the risk for insulin resistance development and new-onset diabetes mellitus in a general population.

特別養護老人ホームにおける介護職の看取りに対する態度に影響を及ぼす要因 : 日本における縦断研究

山本道代, 大浦麻絵, 山本武志, 和泉比佐子, 鈴村美和, 大西浩文, 森満

札幌医学雑誌 ( 札幌医科大学医学部 ) 85 ( 1-6 ) 39 - 45 2016年12月

Aim: The aim of the present study was to clarify that the effects of accumulated experience in end-of-life care and communication skill on the attitudes of care workers' toward end-of-life care. Methods: A study implemented 2012 to 2014. Two hundred and fifty-three questionnaires were returned (40.2%), and 170 were fully completed by care workers in special nursing homes. We sorted the responses into two groups by experience level: the experienced end-of-life care (EE) group and the inexperience end-of-life care (IE) group. Responses were also sorted by communication skill level: a high score communication (HSC) group and a low score communication (LSC) group. A two-way repeated measure analysis of variance was used for the statistical analysis. Results: The EE group was more likely to be younger (P = .04), to have a longer duration of employment (P < .001), and to have participated in an EOL care seminar in their facility (P = .02) than the IE group. Attitudes toward end-of-life care were significantly different between the EE and IE groups (df = 2, F = 3.35, P < .05). Attitudes toward end-of-life care were not significantly different when comparing the HSC and LSC groups (df = 2, F = 0.17, P = .85). The communication skill between the HSC and LSC groups differed significantly at 2012, 2013, and 2014. Conclusions: The accumulation of end-of-life care experience prompted a positive change in attitudes toward end-of-life care. Meanwhile, communication skill had no significant effect to change attitudes toward end-of-life care.

介護職の看取りに対する態度と勤務継続の関連性の検討縦断調査による介護職継続群と脱落群の比較検討より

山本道代, 大西浩文, 山本武志, 高橋順子, 和泉比佐子, 鈴村美和, 森満

日本老年医学会雑誌 ( (一社)日本老年医学会 ) 53 ( 4 ) 442 - 442 2016年10月

Validation of the Japanese disease severity classification and the GAP model in Japanese patients with idiopathic pulmonary fibrosis

Shun Kondoh, Hirofumi Chiba, Hirotaka Nishikiori, Yasuaki Umeda, Koji Kuronuma, Mitsuo Otsuka, Gen Yamada, Hirofumi Ohnishi, Mitsuru Mori, Yasuhiro Kondoh, Hiroyuki Taniguchi, Sakae Homma, Hiroki Takahashi

Respiratory Investigation ( Elsevier B.V. ) 54 ( 5 ) 327 - 333 2016年09月 [査読有り]

Background The clinical course of idiopathic pulmonary fibrosis (IPF) shows great inter-individual differences. It is important to standardize the severity classification to accurately evaluate each patient׳s prognosis. In Japan, an original severity classification (the Japanese disease severity classification, JSC) is used. In the United States, the new multidimensional index and staging system (the GAP model) has been proposed. The objective of this study was to evaluate the model performance for the prediction of mortality risk of the JSC and GAP models using a large cohort of Japanese patients with IPF. Methods This is a retrospective cohort study including 326 patients with IPF in the Hokkaido prefecture from 2003 to 2007. We obtained the survival curves of each stage of the GAP and JSC models to perform a comparison. In the GAP model, the prognostic value for mortality risk of Japanese patients was also evaluated. Results In the JSC, patient prognoses were roughly divided into two groups, mild cases (Stages I and II) and severe cases (Stages III and IV). In the GAP model, there was no significant difference in survival between Stages II and III, and the mortality rates in the patients classified into the GAP Stages I and II were underestimated. Conclusions It is difficult to predict accurate prognosis of IPF using the JSC and the GAP models. A re-examination of the variables from the two models is required, as well as an evaluation of the prognostic value to revise the severity classification for Japanese patients with IPF.

Relationship of serum levels and dietary intake of isoflavone, and the novel bacterium Slackia sp strain NATTS with the risk of prostate cancer: a case-control study among Japanese men

Yoshie Nagata, Yukiko Sugiyama, Fumimasa Fukuta, Akio Takayanagi, Naoya Masumori, Taiji Tsukamoto, Hiroshi Akasaka, Hirofumi Ohnishi, Shigeyuki Saitoh, Tetsuji Miura, Kaoru Moriyama, Hirokazu Tsuji, Hideyuki Akaza, Mitsuru Mori

INTERNATIONAL UROLOGY AND NEPHROLOGY ( SPRINGER ) 48 ( 9 ) 1453 - 1460 2016年09月 [査読有り]

Isoflavones may play a role in the prevention of hormone-related cancers. Equol is an isoflavone metabolized from daidzein in the presence of certain intestinal bacteria. Slackia sp. strain NATTS, a newly identified equol-producing bacterium, was recently isolated from human feces in Japan. We investigated the association of serum levels and dietary intake of isoflavones and Slackia sp. strain NATTS with the risk of prostate cancer in a case-control study among Japanese men. Fifty-six patients with newly diagnosed prostate cancer and 56 hospital controls were enrolled in this study. Isoflavones were assessed by measurement of serum levels and administration of a food frequency questionnaire. Slackia sp. strain NATTS in feces was also measured. The odds ratios (ORs) and 95 % confidence intervals (CIs) for prostate cancer were then determined using a logistic regression model. The adjusted ORs for prostate cancer in comparison with the highest to lowest categories were 0.06 (95 % CI 0.02-0.24) for serum genistein, 0.18 (95 % CI 0.06-0.52) for daidzein, 0.16 (95 % CI 0.06-0.46) for glycitein, 0.52 (95 % CI 0.22-1.22) for equol, 0.86 (95 % CI 0.30-2.48) for dietary genistein, and 0.80 (95 % CI 0.28-2.28) for dietary daidzein. The adjusted OR for prostate cancer in comparison with values above versus below the median was 0.95 (95 % CI 0.42-2.16) for Slackia sp. strain NATTS. Our study findings suggest that high serum levels of genistein, daidzein, and glycitein are significantly associated with a decreased risk of prostate cancer among Japanese men.

Impact of longitudinal status change in metabolic syndrome defined by two different criteria on new onset of type 2 diabetes in a general Japanese population: the Tanno-Sobetsu Study

Hirofumi Ohnishi, Shigeyuki Saitoh, Hiroshi Akasaka, Tetsuaki Furukawa, Mitsuru Mori, Tetsuji Miura

DIABETOLOGY & METABOLIC SYNDROME ( BIOMED CENTRAL LTD ) 8 ( 1 ) 64 2016年09月 [査読有り]

Background: We investigated the effect of longitudinal status change in metabolic syndrome (MetS) assessed by two different criteria on new onset of type 2 diabetes (NODM) in a Japanese population. Methods: The participants were 827 non-diabetic citizens who had undergone medical examinations in 1994 and 2003 or 2004. We used two different criteria of MetS: the interim criteria by 6 institutions (MetS-INT) and Japanese criteria (MetS-JP). According to the interim criteria, individuals defined as having MetS have any three of the following five components of MetS: obesity, hyperglycemia, high blood pressure, hypertriglyceridemia and low HDL cholestero-lemia. According to the Japanese criteria, individuals defined as having MetS must have abdominal obesity plus any two of the following three factors; hyperglycemia, high blood pressure and dyslipidemia (hypertriglyceridemia and/or low HDL-cholesterolemia). According to the status change in MetS, participants were divided into four groups: a non-MetS to non-MetS group, a non-MetS to MetS group, a MetS to non-MetS group and a MetS to MetS group. We calculated odds ratios of these four groups for NODM. Results: NODM occurred in 65 participants. The odds ratios for NODM were 4.86, 4.97 and 7.50 in the non-MetS-INT to MetS-INT group, MetS-INT to non-MetS-INT group and MetS-INT to MetS-INT group, respectively. On the other hand, the odds ratios were 4.28 and 15.55 in the non-MetS-JP to MetS-JP group and MetS-JP to MetS-JP group, respectively. After adjustment for high fasting plasma glucose at baseline, magnitude of the odds ratio of MetS to MetS group was larger in the Japanese criteria group than in the interim criteria group. Conclusions: Determining the status of MetS routinely and paying attention to status change in MetS may be important for prevention of type 2 diabetes. MetS defined by the criteria which includes obesity as a prerequisite component may be a stronger risk for type 2 diabetes than MetS defined by the criteria which includes obesity as one of components.

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