研究者詳細 - 大西　浩文

論文 - 大西　浩文

分割表示 >> ／全件表示 279 件中 1 - 279 件目

Machine learning-based analyses of contributing factors for the development of hypertension: a comparative study.

Marenao Tanaka, Yukinori Akiyama, Kazuma Mori, Itaru Hosaka, Keisuke Endo, Toshifumi Ogawa, Tatsuya Sato, Toru Suzuki, Toshiyuki Yano, Hirofumi Ohnishi, Nagisa Hanawa, Masato Furuhashi

Clinical and experimental hypertension (New York, N.Y. : 1993) 47 ( 1 ) 2449613 - 2449613 2025年12月 [国際誌]

OBJECTIVES: Sufficient attention has not been given to machine learning (ML) models using longitudinal data for investigating important predictors of new onset of hypertension. We investigated the predictive ability of several ML models for the development of hypertension. METHODS: A total of 15 965 Japanese participants (men/women: 9,466/6,499, mean age: 45 years) who received annual health examinations were randomly divided into a training group (70%, n = 11,175) and a test group (30%, n = 4,790). The predictive abilities of 58 candidates including fatty liver index (FLI), which is calculated by using body mass index, waist circumference and levels of γ-glutamyl transferase and triglycerides, were investigated by statistics analogous to the area under the curve (AUC) in receiver operating characteristic curve analyses using ML models including logistic regression, random forest, naïve Bayes, extreme gradient boosting and artificial neural network. RESULTS: During a 10-year period (mean period: 6.1 years), 2,132 subjects (19.1%) in the training group and 917 subjects (19.1%) in the test group had new onset of hypertension. Among the 58 parameters, systolic blood pressure, age and FLI were identified as important candidates by random forest feature selection with 10-fold cross-validation. The AUCs of ML models were 0.765-0.825, and discriminatory capacity was significantly improved in the artificial neural network model compared to that in the logistic regression model. CONCLUSIONS: The development of hypertension can be simply and accurately predicted by each ML model using systolic blood pressure, age and FLI as selected features. By building multiple ML models, more practical prediction might be possible.

Biomechanical effects of fascial hydrorelease: a cadaveric study

Kousuke Shiwaku, Hidenori Otsubo, Daisuke Suzuki, Calmero Pirri, Taiki Kodesyo, Tomoaki Kamiya, Keigo Taniguchi, Hirofumi Ohnishi, Atsushi Teramoto, Carla Stecco

BMC Musculoskeletal Disorders ( Springer Science and Business Media LLC ) 26 ( 1 ) 2025年03月

Utility of a Wearable Tracker to Assess Sleep Quality in Nurses and Their Spouses: A Prospective Cohort Study

Tomohiro Ishinuki, Erika Goda, Hiroomi Tatsumi, Goro Kutomi, Toshio Ohyanagi, Hirofumi Ohnishi, Yoshiki Masuda, Thomas T. Hui, Toru Mizuguchi

SAGE Open Nursing ( SAGE Publications ) 11 2025年01月

Introduction Sleep disturbances among nurses engaged in night duty and their spouses need to be improved to ensure their ability to provide care and perform daily tasks. Therefore, an objective investigation is needed to establish a sleep improvement strategy. Objective To investigate the utility of a sleep tracker to assess sleep quality in nurses and spouses. Method Nurses ( n = 30) and spouses ( n = 30) wore a sleep tracker for 14 days to investigate sleep scores. Sleep quality and number of steps were evaluated by Fitbit. They responded to the Richards-Campbell Sleep Questionnaire and Pittsburgh Sleep Quality Index. A multiple regression analysis was performed to identify the factors affecting sleep quality. Results Factors affecting sleep scores in nurses were hypnotic medication, night duty, and steps, while those in spouses were mental instability, hypnotic medication, alcohol, night duty, and steps. Factors affecting the Richards-Campbell Sleep Questionnaire in nurses were household chores, night duty, and steps, while those in spouses were hypnotic medication and steps. Conclusion The sleep quality of nurses was affected by household chores, hypnotic medication, night duty, and steps. Besides the factors of nurses, spouses were affected by mental instability and alcohol. Night duty affected negativity in both nurses and spouses. Steps exerted positive effects in both the sleep tracker and the Richards-Campbell Sleep Questionnaire. The sleep tracker may be useful for identifying factors that improve sleep quality.

The serum γ-Glutamyltransferase Level is Associated with the Development of Hypertension in Alcohol Infrequent Drinkers but not in Frequent Drinkers

Kazuma Mori, Marenao Tanaka, Tatsuya Sato, Yukinori Akiyama, Hirofumi Ohnishi, Nagisa Hanawa, Masato Furuhashi

Internal Medicine ( Japanese Society of Internal Medicine ) 2025年

Maternal age and the rising incidence of hypertensive disorders of pregnancy: A comprehensive analysis of national claims data from Japan.

Naomi Maeda, Masayuki Koyama, Shintaro Takatsuka, Keisuke Oyatani, Nobuaki Himuro, Tasuku Mariya, Yoshika Kuno, Shiro Hinotsu, Tsuyoshi Saito, Hirofumi Ohnishi

PloS one 20 ( 2 ) e0319177 2025年 [国際誌]

BACKGROUND: Hypertensive disorders of pregnancy (HDP) significantly increase the risk of developing hypertension and cardiovascular disease (CVD) later in life and are a major cause of maternal mortality. However, little is known about the nationwide, long-term, all-inclusive status of HDP. OBJECTIVE: To estimate the incidence of HDP from 2011 to 2019 in Hokkaido, Japan, with a focus on age groups. METHODS: Using National Database (NDB) insurance medical data, a retrospective analysis was conducted. Due to the absence of direct pregnancy data, birth numbers were used as a surrogate for the number of pregnant women to calculate the incidence of HDP. RESULTS: The average incidence rate of HDP over 9 years was 6.37%. The incidence rate was lowest among women aged 25-29 years, at 5.58% (95% confidence interval [CI]: 5.43-5.73), and increased with age, peaking at 10.58% (95% CI: 10.10-11.09) among women over 40 years. Notably, the incidence rate for women under 20 years of age was 6.70% (95% CI: 5.97-7.51), which was higher than that for women in their 20s. A mean annual increase of 0.25% in age-adjusted incidence was observed during this period, which was statistically significant (R² = 0.87, p < 0.01). CONCLUSION: This study reveals that the risk of developing HDP is associated with both older childbearing and younger pregnancies and follows a J-curve, suggesting that factors other than maternal aging also contribute to the increased incidence of HDP and that further research on risk factors for HDP, which is on the rise worldwide, is urgently needed.

High Intraocular Pressure Is Independently Associated With New-Onset Systemic Hypertension Over a 10-Year Period

Araya Umetsu, Marenao Tanaka, Tatsuya Sato, Yukinori Akiyama, Keisuke Endo, Kazuma Mori, Hirofumi Ohnishi, Megumi Watanabe, Hiroshi Ohguro, Nagisa Hanawa, Masato Furuhashi

Circulation Journal ( Japanese Circulation Society ) 2024年07月

Prediction of the future number of fall-related emergency medical services calls in older individuals.

Shuji Uemura, Ryuichi Nakayama, Masayuki Koyama, Yukiko Taguchi, Naofumi Bunya, Keigo Sawamoto, Hirofumi Ohnishi, Eichi Narimatsu

International journal of emergency medicine 17 ( 1 ) 72 - 72 2024年06月 [国際誌]

BACKGROUND: Falls among older individuals contribute significantly to the rise in ambulance transport use. To recognize the importance of future countermeasures, we estimated the projected number and percentage of fall-related emergency medical service (EMS) calls. METHODS: We examined the sex, age group, and location of falls among patients aged ≥ 65 years who contacted emergency services in Sapporo City from 2013 to 2021. Annual fall-related calls per population subgroup were calculated, and trends were analyzed. Four models were used to estimate the future number of fall-related calls from the 2025-2060 projected population: (1) based on the 2022 data, estimates from the 2013-2022 data using (2) Poisson progression, (3) neural network, (4) estimates from the 2013-2019 data using neural network. The number of all EMS calls was also determined using the same method to obtain the ratio of all EMS calls. RESULTS: During 2013-2022, 70,262 fall-related calls were made for those aged ≥ 65 years. The rate was higher indoors among females and outdoor among males in most age groups and generally increased with age. After adjusting for age, the rate increased by year. Future estimates of the number of fall calls are approximately double the number in 2022 in 2040 and three times in 2060, with falls accounting for approximately 11% and 13% of all EMS calls in 2040 and 2060, respectively. CONCLUSION: The number of fall-related EMS calls among older people is expected to increase in the future, and the percentage of EMS calls will also increase; therefore, countermeasures are urgently needed.

慢性腎臓病と代謝異常関連脂肪肝疾患(MAFLD)との合併は虚血性心疾患の発症リスクを増加させる

宮森大輔, 田中希尚, 佐藤達也, 遠藤圭佑, 森和真, 塙なぎさ, 大西浩文, 古橋眞人

日本腎臓学会誌 ( (一社)日本腎臓学会 ) 66 ( 4 ) 652 - 652 2024年06月

慢性腎臓病と代謝異常関連脂肪肝疾患(MAFLD)との合併は虚血性心疾患の発症リスクを増加させる

宮森大輔, 田中希尚, 佐藤達也, 遠藤圭佑, 森和真, 塙なぎさ, 大西浩文, 古橋眞人

日本腎臓学会誌 ( (一社)日本腎臓学会 ) 66 ( 4 ) 652 - 652 2024年06月

Cross-cultural adaptation, validity and reliability of the Japanese version of ABILHAND-kids for children with cerebral palsy using Rasch measurement model.

Sayaka Katori, Nobuaki Himuro, Yukihiro Kitai, Ryo Tanabe, Hirofumi Ohnishi

Disability and rehabilitation 1 - 9 2024年04月 [国際誌]

PURPOSE: The aim of this study was to develop the Japanese version of the ABILHAND-Kids and to examine its psychometric properties for Japanese children with cerebral palsy (CP). METHODS: The experimental version of 75 items was developed using forward-backward translation method. Parents of 137 children with CP answered it. Their responses were analyzed to successive items, and psychometric properties of the final version were investigated through the Rasch measurement model. RESULTS: The Japanese version of the ABILHAND-Kids contained 22 items. It showed valid item-patient targeting, no significant floor and ceiling effects, and no differential item functioning for demographic and clinical subgroups. All items contributed to the definition of one-dimensional measure. For internal consistency, the person separation index was 0.94. For test-retest reliability, the intraclass correlation coefficients were 0.96 (95% CI: 0.92-0.98). The minimal detectable difference was calculated with a logit score of 0.79 and a total raw score of 4.50. The logit score showed a strong correlation with the Manual Ability Classification System level (ρ= -0.70) and the Gross Motor Function Classification System level (ρ= -0.62). CONCLUSIONS: The Japanese version of the ABILHAND-Kids was found to be valid and reliable. It appears to be a good tool for assessing manual abilities in daily activities in children with CP.

Sampsonの式あるいは人工知能を用いて推定したsmall dense LDLコレステロール値の精度の検証

大久保武志, 遠藤圭佑, 田中希尚, 佐藤達也, 小林亮, 田中真輝人, 秋山幸功, 保坂到, 中田圭, 小山雅之, 大西浩文, 高橋聡, 古橋眞人

糖尿病 ( (一社)日本糖尿病学会 ) 67 ( Suppl.1 ) S - 251 2024年04月

Sampsonの式あるいは人工知能を用いて推定したsmall dense LDLコレステロール値の精度の検証

大久保武志, 遠藤圭佑, 田中希尚, 佐藤達也, 小林亮, 田中真輝人, 秋山幸功, 保坂到, 中田圭, 小山雅之, 大西浩文, 高橋聡, 古橋眞人

糖尿病 ( (一社)日本糖尿病学会 ) 67 ( Suppl.1 ) S - 251 2024年04月

Sampson方程式による小型低密度リポ蛋白質コレステロールは虚血性心疾患発症の優れた予測因子である

印鑰雅史, 佐藤達也, 佐藤達也, 田中希尚, 田中希尚, 遠藤圭佑, 保坂到, 三上拓真, 大西浩文, 塙なぎさ, 古橋眞人

日本循環器学会学術集会(Web) ( (一社)日本循環器学会 ) 88回 OJ03 - 2 2024年03月

Sampsonの式で算出したsmall dense LDLコレステロールは虚血性心疾患発症の有力な予測因子である(Calculated Small Dense Low-density Lipoprotein Cholesterol by Sampson Equation is a Predominant Predictor for the Development of Ischemic Heart Disease)

印鑰雅史, 佐藤達也, 田中希尚, 遠藤圭佑, 保坂到, 三上拓真, 大西浩文, 塙なぎさ, 古橋眞人

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 ) 88回 OJ03 - 2 2024年03月

児童の手洗いを科学するアクションリサーチ ATPを用いた可視化の検討

大浦麻絵, 中田圭, 内藤由紀子, 大岩大祐, 小山雅之, 長多好恵, 助友裕子, 大西浩文

北海道公衆衛生学雑誌 ( 北海道公衆衛生学会 ) 37 ( 2 ) 65 - 69 2024年03月

目的:小学校教育において実践している手洗い健康教育プログラムに新たにATP(アデノシン三リン酸)検査を導入した.科学的な指標を用い,児童の手の汚れを可視化させた.汚れの可視化を導入した手洗い教育プログラムの有効性に関する資料とすることを目的とした.方法:北海道札幌市公立小学校の放課後教室でpilot studyを実施した.16人の児童に対し,IDで連結した無記名自記式アンケート調査と手洗い前後のATP検査を実施した.結果:全体における手洗い後のATP値は(中央値(四分位範囲)=4968.5(3589.0,7481.8)であり手洗い前(67738.0(56702.5,85732.5))と比べて減少していた(p<0.05).3～5年生に限定しても,手洗い後のATP値(4739.0[3249.0,7481.8])は手洗い前(67738.0[58527.3,85732.5])に比べて減少していた(p<0.05).1,2年生においては,差は認められなかった(p=0.07).活動評価:発達がより一律となる高学年の方がより深い理解や応用的な考え方が出来ることで,手洗いが上手であった可能性が考えられた.ATP検査は客観的指標として手洗い力などとして教育効果を測る新たな視点として有効であることが示唆された.(著者抄録)

子ども達から子ども達へ伝えるピア健康教育の実践病気の予防プロジェクト2022

大浦麻絵, 大西浩文, 中田真由, 小山雅之, 中田圭, 長多好恵, 長谷川準子, 助友裕子, 森満

北海道公衆衛生学雑誌 ( 北海道公衆衛生学会 ) 37 ( 2 ) 137 - 141 2024年03月

本稿では札幌市内小中学校を中心として取り組んでいる「病気の予防プロジェクト」より2022年度に実施した札幌市立小学校2校での活動を紹介する.病気の予防プロジェクトは,子ども達が主体的にエビデンス(科学的根拠)に基づいた知識を学び,学びを深化させ,他者に情報発信するActive Learningプログラムである.N小学校では6年生は他校の生徒や札幌市民へ,F小学校では3年生が1,2年生を中心に全校へ向け情報発信を行った."コロナ禍において,自分達にも何かできることはないだろうか?"子ども達の素直な気持ちを活かした健康教育活動とするため,学校と学校を取り巻く地域資源の一つである大学の研究班とが連携して実施した.本活動は健康教育が目指すセルフエスティームを基盤としており,活動状況から子ども達の社会性,自己肯定感を自然な形で育むことが出来る可能性が考えられた.(著者抄録)

脳性麻痺児における介助のしやすさに関連する因子の特定システマティックレビュー

井上孝仁, 和泉裕斗, 樋室伸顕, 西部寿人, 井上和広, 藤坂広幸, 大西浩文

小児理学療法学 ( (一社)日本小児理学療法学会 ) 2 ( Suppl.1 ) 122 - 122 2024年03月

The Contributions of Knee Extension Strength and Hand Grip Strength to Factors Relevant to Physical Frailty: The Tanno-Sobetsu Study.

Toshiaki Seko, Hiroshi Akasaka, Masayuki Koyama, Nobuaki Himuro, Shigeyuki Saitoh, Shunichi Ogawa, Sayo Miura, Mitsuru Mori, Hirofumi Ohnishi

Geriatrics (Basel, Switzerland) 9 ( 1 ) 2024年01月 [国際誌]

Sarcopenia is the core factor of frailty. This study specifically focused on lower limb muscle strength and examined muscle indices that indicate the risk of frailty or pre-frailty in older adults. The study included 327 community-dwelling individuals aged ≥65 years (43.7% male) who participated in the cohort. Frailty was defined based on five symptoms: weight loss, low activity level, exhaustion, weakness and slowness. Participants were classified into frail (three or more applicable), pre-frail (one to two applicable) and non-frail groups. Muscle strength (knee extension strength, toe grip strength and hand grip strength) were assessed, and appendicular muscle mass was assessed via a bioelectrical impedance analysis. The adjusted odds ratio (OR) of muscle indices for with frailty (frail group vs. pre-frail group) or pre-frailty (pre-frail group vs. non-frail group) were calculated. The prevalence of frail and pre-frail was 7% and 40%, respectively. Adjusted for age, sex, albumin and medical history, knee extension strength was significantly associated with frailty (odds ratio 0.95, 95% CI 0.92-0.98), while hand grip strength was associated with pre-frailty (odds ratio 0.92, 95% CI 0.88-0.97) but not with other muscle indices. This study is significant for identifying knee extension strength as a factor relevant to frailty in older adults considered pre-frailty, emphasizing the importance of this specific muscle measure in predicting and managing frailty.

Science behind children's handwashing: action study of 9- to 10-years-old elementary school students in Japan.

Asae Oura, Yukiko Naito, Hiroko Yako-Suketomo, Kei Nakata, Masayuki Koyama, Hirofumi Ohnishi

Frontiers in public health 12 1425646 - 1425646 2024年 [国際誌]

BACKGROUND: Hand washing instructions for children have been implemented in school education to establish good lifestyle habits. However, repeated hand washing through education from early childhood was common for both teachers and children. If this continues, children might assume they already know how to wash their hands, stop taking handwashing instructions seriously, and become increasingly lax about washing their hands. PURPOSE: This study aimed to develop a new handwashing education method for children. METHODS: We applied the adenosine triphosphate (ATP) test to health education on hand washing in elementary schools. This study was conducted as part of a class for elementary school students in October 2023, in Hokkaido, Japan. The subjects were 157 third-grade (9-10 years old) elementary school students. After excluding absent pupils, 147 were included in the analysis. RESULTS: Both pre- and post-education, ATP values after handwashing were lower than those before handwashing. Following the education, children's handwashing behavior improved, with an increase in the number of point washed and appropriate timing of handwashing. CONCLUSION: The new handwashing education program utilizing the ATP-test succeeded in promoting handwashing behavior among many children. Visualizing handwashing using ATP values was effective in motivating children.

Validation of Estimated Small Dense Low-Density Lipoprotein Cholesterol Concentration in a Japanese General Population.

Keisuke Endo, Ryo Kobayashi, Makito Tanaka, Marenao Tanaka, Yukinori Akiyama, Tatsuya Sato, Itaru Hosaka, Kei Nakata, Masayuki Koyama, Hirofumi Ohnishi, Satoshi Takahashi, Masato Furuhashi

Journal of atherosclerosis and thrombosis 2023年12月 [国内誌]

AIM: A high level of directly measured small dense low-density lipoprotein cholesterol (sdLDL-C) is a strong risk factor for atherosclerotic cardiovascular disease. A method for estimating sdLDL-C by using Sampson's equation that includes levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), non-HDL-C and triglycerides (TG) has recently been proposed. We investigated the validation and exploration of estimated sdLDL-C level. METHODS: The associations between measured and estimated sdLDL-C levels were investigated in 605 Japanese subjects (men/women: 280/325; mean age: 65±15 years) who received annual health check-ups in the Tanno Sobetsu Study, a population-based cohort. RESULTS: Estimated sdLDL-C level was highly correlated with measured sdLDL-C level in all subjects (R2 =0.701), nondiabetic subjects without any medication (n=254, R 2=0.686) and subjects with diabetes mellitus (n=128, R2=0.721). Multivariable regression analysis showed that levels of non-HDL-C, TG and γ-glutamyl transpeptidase (γGTP) were independent predictors of measured sdLDL-C level. In a stratification of the LDL window, all of the subjects with a combination of high non-HDL-C (≥ 170 mg/dL) and high TG (≥ 150 mg/dL) had high levels of measured and estimated sdLDL-C (≥ 35 mg/dL). Furthermore, machine learning-based estimation of sdLDL-C level by artificial intelligence software, Prediction One, was substantially improved by using components of Sampson's equation (R2=0.803) and by using those components with the addition of γGTP and deletion of TC (R2=0.929). CONCLUSIONS: sdLDL-C level estimated by Sampson's equation can be used instead of measured sdLDL-C level in general practice. By building multiple machine learning models of artificial intelligence, a more accurate and practical estimation of sdLDL-C level might be possible.

Reconsidering resectable oncological conditions in pancreatic tail cancer: A multicenter retrospective study on prognostic factors in pancreatic tail cancer after resection (HOPS Pt-01).

Yasutoshi Kimura, Toru Nakamura, Masafumi Imamura, Minoru Nagayama, Takeshi Murakami, Tsuyoshi Hayashi, Toru Kato, Kimitaka Tanaka, Makoto Yoshida, Kazuharu Kukita, Koji Imai, Makoto Yoshida, Yoshiharu Masaki, Masayo Motoya, Masaki Kuwatani, Masayuki Koyama, Hirofumi Ohnishi, Ichiro Takemasa

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2023年12月 [国際誌]

BACKGROUND: Pancreatic tail cancer (Pt-PC) is generally considered resectable when metastasis is absent, but doubts persist in clinical practice due to the variability in local tumor extent. We conducted a multicenter retrospective study to comprehensively identify prognostic factors associated with Pt-PC after resection. METHODS: We enrolled 100 patients that underwent distal pancreatectomy. The optimal combination of factors influencing relapse-free survival (RFS) was determined using the maximum likelihood method (MLM) and corrected Akaike and Bayesian information criteria (AICc and BIC). Prognostic elements were then validated to predict oncological outcomes. RESULTS: Therapeutic interventions included neoadjuvant treatment in 16 patients and concomitant visceral resection (CVR) in 37 patients; 89 patients achieved R0. Median RFS and OS after surgery were 23.1 and 37.1 months, respectively. AICc/BIC were minimized in the model with ASA-PS (≥2), CA19-9 (≥112 U/mL at baseline, non-normalized postoperatively), need for CVR, 6 pathological items (tumor diameter ≥19.5 mm, histology G1, invasion of the anterior pancreatic border, splenic vein invasion, splenic artery invasion, lymph node metastasis), and completed adjuvant treatment (cAT) for RFS. Regarding the predictive value of these 11 factors, area under the curve was 0.842 for 5-year RFS. Multivariate analysis of these 11 factors showed that predictors of RFS include CVR (hazard ratio, 2.13; 95 % confidence interval, 1.08-4.19; p = 0.028) and cAT (0.38, 0.19-0.76; p = 0.006). CONCLUSIONS: The MLM identified certain Pt-PC cases warranting consideration beyond resectable during clinical management. Particular attention should be paid to conditions requiring CVR, even though immortal time bias remains unresolved with adjuvant treatment.

Predictive modeling for the development of diabetes mellitus using key factors in various machine learning approaches

Marenao Tanaka, Yukinori Akiyama, Kazuma Mori, Itaru Hosaka, Kenichi Kato, Keisuke Endo, Toshifumi Ogawa, Tatsuya Sato, Toru Suzuki, Toshiyuki Yano, Hirofumi Ohnishi, Nagisa Hanawa, Masato Furuhashi

Diabetes Epidemiology and Management ( Elsevier BV ) 100191 - 100191 2023年12月

ECMOを要するCOVID-19患者における高流量酸素療法の影響について STF ECMO alliance

文屋尚史, 濱口純, 星野耕大, 中山龍一, 和田健志郎, 丸山隼一, 佐藤裕一, 郭光徳, 大西浩文, 成松英智, 石倉宏恭, 清水敬樹

日本救急医学会雑誌 ( (一社)日本救急医学会 ) 34 ( 12 ) 716 - 716 2023年12月

Circulating T follicular helper 2 cells, T follicular regulatory cells and regulatory B cells are effective biomarkers for predicting the response to house dust mite sublingual immunotherapy in patients with allergic respiratory diseases

Katsunori Shigehara, Ryuta Kamekura, Ippei Ikegami, Hiroshi Sakamoto, Masahiro Yanagi, Shiori Kamiya, Kentaro Kodama, Yuichiro Asai, Satsuki Miyajima, Hirotaka Nishikiori, Eiji Uno, Keisuke Yamamoto, Kenichi Takano, Hirofumi Chiba, Hirofumi Ohnishi, Shingo Ichimiya

Frontiers in Immunology ( Frontiers Media SA ) 14 2023年11月

The relationships between T follicular helper (Tfh) cells and antigen-specific immunoglobulins (sIgs) in patients with allergic respiratory diseases who are receiving antigen immunotherapy (AIT) have not been fully clarified. Therefore, we started to perform house dust mite sublingual immunotherapy (HDM-SLIT) for 20 patients with atopic asthma comorbid with allergic rhinitis (AA+AR) who were already receiving ordinary treatments including inhaled corticosteroid (ICS). We examined percentages of circulating T follicular helper (cTfh) and regulatory (cTfr) cells and percentages of circulating regulatory T (cTreg) and B (cBreg) cells by FACS and we examined levels of Der-p/f sIgs by ELISA. Based on the symptom score (asthma control questionnaire: ACQ) and medication score ((global initiative for asthma: GINA) treatment step score) in patients with AA, the patients were divided into responders and non-responders. The percentage of cTfh2 cells significantly decreased and the percentage of cTfh1 cells significantly increased within the first year. Der-p/f sIgEs decreased after a transient elevation at 3 months in both groups. Notably, the percentage of cTfh2 cells and the ratio of cTfh2/cBreg cells and Der-p/f sIgEs greatly decreased in responders from 6 months to 12 months. The percentages of cTfr and cTreg cells showed significant negative correlations with the percentage of cTfh2 cells. The percentage of IL-4⁺ cTfh cells were significantly decreased and the percentage of IFN-γ⁺ cTfh cells were increased before treatment to 24 months in 6 patients examined (4 responders and 2 non-responders). We performed multi plelogistic regression analysis based on these results, the ratios of cTfh2/cTfr cells and cTfh2/cBreg cells at the start of therapy were statistically effective biomarkers for predicting the response to HDM-SLIT in patients with AA+AR.

A high level of thyroid-stimulating hormone is a risk factor for the development of chronic kidney disease in men: a 10-year cohort study.

Keisuke Endo, Marenao Tanaka, Tatsuya Sato, Kazuma Mori, Itaru Hosaka, Takuma Mikami, Araya Umetsu, Yukinori Akiyama, Hirofumi Ohnishi, Nagisa Hanawa, Masato Furuhashi

Hypertension research : official journal of the Japanese Society of Hypertension 2023年10月 [国際誌]

Hypothyroidism has been reported to be associated with chronic kidney disease (CKD). However, the impact of thyroid-stimulating hormone (TSH) on new onset of CKD and its gender dependence remain undetermined. We investigated the association of serum TSH level and the development of CKD defined by estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or positive for urine protein in 28,990 Japanese subjects who received annual health examinations. After excluding subjects with no data for serum TSH, urinalysis and eGFR and those with CKD at baseline, a total of 10,392 subjects (men/women: 6802/3590, mean age: 48 years) were recruited. During a 10-year follow-up, 1185 men (6.7%) and 578 women (2.9%) newly developed CKD. Multivariable Cox proportional hazard models after adjustment of age, body mass index, smoking habit, hypertension, diabetes mellitus, dyslipidemia, ischemic heart disease and eGFR (≥ 90 mL/min/1.73 m2) showed that the hazard ratio (HR) for the development of CKD in the high TSH (> 4.2 mU/L) group was significantly higher than that in the low TSH (≤ 4.2 mU/L) group in men (HR [95% confidence interval]: 1.41 [1.09-1.83]) but not in women (1.08 [0.77-1.51]). There was a significant interaction between sex and the category of TSH level for the development of CKD (p = 0.02). The adjusted HR with a restricted cubic spline increased with a higher level of TSH in men but not in women. In conclusion, a high level of TSH is associated with an increased risk for the development of CKD in men but not in women.

オンラインPRO情報システムによるがん手術患者の術創部感染症の危険因子と予後の検証

石貫智裕, 久冨五郎, 島宏彰, 和田朝香, 青木武士, 吉田寛, 渡邉学, 長田拓哉, 横尾英樹, 問山裕二, 大西浩文, 林宏至, 森脇健介, 大柳俊夫, 水口徹

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 ) 61回 P61 - 5 2023年10月

北海道の妊娠高血圧症候群の実態調査 NDBを用いた悉皆調査

前田尚美, 小山雅之, 高塚伸太朗, 親谷佳佑, 中田圭, 樋室伸顕, 大西浩文

日本高血圧学会総会プログラム・抄録集 ( (NPO)日本高血圧学会 ) 45回 415 - 415 2023年09月

一般住宅と高齢者施設から救急要請された高齢者転倒患者の比較

上村修二, 中山龍一, 小山雅之, 原正浩, 田口裕紀子, 大西浩文, 成松英智

日本転倒予防学会誌 ( 日本転倒予防学会 ) ( 第10回学術集会 ) 150 - 150 2023年09月

Calculated Small Dense Low-Density Lipoprotein Cholesterol Level is A Predominant Predictor for New Onset of Ischemic Heart Disease.

Masafumi Inyaku, Marenao Tanaka, Tatsuya Sato, Keisuke Endo, Kazuma Mori, Itaru Hosaka, Takuma Mikami, Araya Umetsu, Hirofumi Ohnishi, Yukinori Akiyama, Nagisa Hanawa, Masato Furuhashi

Journal of atherosclerosis and thrombosis 2023年08月 [国内誌]

AIM: A high level of directly measured small dense low-density lipoprotein cholesterol (sdLDL-C) is a strong risk factor for ischemic heart disease (IHD). However, it remains unclear whether estimated sdLDL-C level is a predictor for IHD. We investigated the associations of new onset of IHD with levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), LDL-C and calculated sdLDL-C by Sampson's equation. METHODS: After exclusion of subjects with IHD or those with TG ≥ 800 mg/dL, a total of 18,176 subjects (men/women: 11,712/6,464, mean age: 46 years) were recruited among 28,990 Japanese individuals who received annual health checkups. RESULTS: During the 10-year follow-up period, 456 men (3.9%) and 121 women (1.9%) newly developed IHD. Multivariable Cox proportional hazard analyses after adjustment of age, sex, obesity, smoking habit, family history of IHD, estimated glomerular filtration rate, hypertension and diabetes mellitus at baseline showed that the hazard ratio (HR) (1.38 [95% confidence interval: 1.03-1.85]) for new onset of IHD in subjects with the 4th quartile (Q4) of sdLDL-C (≥ 42 mg/dL) was significantly higher than that in subjects with the 1st quartile (Q1) (≤ 24 mg/dL) as the reference, though the adjusted HRs in subjects with Q2-Q4 of TC, HDL-C, non-HDL-C, LDL-C and TG were comparable with those in subjects with Q1 of the respective lipid fractions. The adjusted HR with a restricted cubic spline increased with a higher level of calculated sdLDL-C as a continuous value at baseline. CONCLUSIONS: sdLDL-C level calculated by Sampson's equation is a predominant predictor for the development of IHD in a general Japanese population.

An increase in calculated small dense low-density lipoprotein cholesterol predicts new onset of hypertension in a Japanese cohort.

Marenao Tanaka, Tatsuya Sato, Keisuke Endo, Masafumi Inyaku, Kazuma Mori, Itaru Hosaka, Takuma Mikami, Yukinori Akiyama, Hirofumi Ohnishi, Nagisa Hanawa, Masato Furuhashi

Hypertension research : official journal of the Japanese Society of Hypertension 2023年08月 [国際誌]

A disorder of lipid metabolism is involved in cardiovascular diseases including hypertension. A high level of small dense low-density lipoprotein cholesterol (sdLDL-C) is a strong risk factor for atherosclerotic cardiovascular disease. However, the association between sdLDL-C and hypertension has not been fully investigated. We investigated the associations between the development of hypertension during a 10-year period and levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), and LDL-C and sdLDL-C calculated by using the Sampson equations in 28,990 Japanese subjects who received annual health examinations. After exclusion of subjects with missing data, those with hypertension, and those with TG ≥ 800 mg/dL at baseline, a total of 15,177 subjects (men/women: 9374/5803, mean age: 46 years) were recruited. During the 10-year period, 2379 men (25.4%) and 724 women (12.5%) had new onset of hypertension. Multivariable Cox proportional hazard model analyses showed that levels of HDL-C, non-HDL-C, TG and sdLDL-C, but not levels of TC and LDL-C, were independent risk factors for the development of hypertension after adjustment of age, sex, family history of hypertension, systolic blood pressure, obesity, current smoking habit, alcohol drinking habit, estimated glomerular filtration rate, diagnosis of diabetes mellitus and use of lipid-lowering drugs and that the adjusted risk of sdLDL-C (per 1-standard deviation) was highest (hazard ratio [95% confidence interval: 1.09 [1.05-1.13]). The addition of sdLDL-C to traditional risk factors for hypertension significantly improved the discriminatory capability, which was better than that of other lipid fractions. In conclusion, a high level of calculated sdLDL-C predicts the development of hypertension.

Coexistence of Metabolic Dysfunction-Associated Fatty Liver Disease and Chronic Kidney Disease Is a More Potent Risk Factor for Ischemic Heart Disease.

Daisuke Miyamori, Marenao Tanaka, Tatsuya Sato, Keisuke Endo, Kazuma Mori, Takuma Mikami, Itaru Hosaka, Nagisa Hanawa, Hirofumi Ohnishi, Masato Furuhashi

Journal of the American Heart Association 12 ( 14 ) e030269 2023年07月 [国際誌]

Background Metabolic dysfunction-associated fatty liver disease (MAFLD), defined as fatty liver with overweight/obesity, type 2 diabetes, or metabolic abnormalities, is a newly proposed disease. However, it remains unclear whether the coexistence of MAFLD and chronic kidney disease (CKD) is a more potent risk factor for ischemic heart disease (IHD). Methods and Results We investigated the risk of the combination of MAFLD and CKD for development of IHD during a 10-year follow-up period in 28 990 Japanese subjects who received annual health examinations. After exclusion of subjects without data for abdominal ultrasonography or with the presence of IHD at baseline, a total of 14 141 subjects (men/women: 9195/4946; mean age, 48 years) were recruited. During the 10-year period (mean, 6.9 years), 479 subjects (men/women, 397/82) had new onset of IHD. Kaplan-Meier survival curves showed significant differences in rates of the cumulative incidence of IHD in subjects with and those without MAFLD (n=4581) and CKD (n=990; stages 1/2/3/4-5, 198/398/375/19). Multivariable Cox proportional hazard model analyses showed that coexistence of MAFLD and CKD, but not MAFLD or CKD alone, was an independent predictor for development of IHD after adjustment for age, sex, current smoking habit, family history of IHD, overweight/obesity, diabetes, hypertension, and dyslipidemia (hazard ratio, 1.51 [95% CI, 1.02-2.22]). The addition of the combination of MAFLD and CKD to traditional risk factors for IHD significantly improved the discriminatory capability. Conclusions The coexistence of MAFLD and CKD predicts new onset of IHD better than does MAFLD or CKD alone.

Extension of Selection Time for the Emergency Destination of Patients with a Fever Due to the Coronavirus Disease 2019 Pandemic: A Difference-in-differences Analysis.

Ryuichi Nakayama, Shuji Uemura, Masayuki Koyama, Masahiro Hara, Naofumi Bunya, Keigo Sawamoto, Hirofumi Ohnishi, Eichi Narimatsu

Internal medicine (Tokyo, Japan) 2023年06月 [国内誌]

Background During the coronavirus disease 2019 (COVID-19) pandemic period, an extended total activity time (TAT) in emergency cases has been reported, especially in febrile patients. A brief selection time (ST) regarding the transport of patients to designated hospitals is vital to achieving a good outcome. However, to our knowledge, no studies have reported the impact of the COVID-19 pandemic on the ST. We therefore examined the impact of a fever on the ST for the transportation of emergency patients during the COVID-19 pandemic. Method We analyzed emergency medical services (EMS) data in Sapporo between January 2015 and December 2020. The primary outcome was the ST for the emergency destination of patients. The secondary outcomes were the number of inquiries, time from emergency call to arrival at the scene [call-to-scene time (CST)], time from arrival at the hospital to return base [arrival-to-return time (ART)], and TAT. We used a multivariable linear regression model to estimate the difference-in-differences effect. Results A total of 383,917 patients who were transported to the hospital were enrolled within the study period. The mean ST was 5.8 min in 2019 and 7.1 min in 2020. The difference-in-differences analyses showed that the mean ST increased by 2.52 min (p<0.001), the mean ART by 3.10 min (p<0.001), and the mean TAT by 7.27 min (p<0.001) for patients with a fever during the COVID-19 period. Conclusions This study showed that febrile patients had a longer ST, ART, and TAT during the 2020 COVID-19 period. Considering the COVID-19 pandemic and the threat of future pandemics, regional infection control and information-sharing should be conducted to reduce the EMS activity time.

Prognostic impact of respiratory dysfunction in elderly patients with cervical spinal cord injury and/or fractures: a multicenter survey.

Ryosuke Hirota, Yoshinori Terashima, Hirofumi Ohnishi, Toshihiko Yamashita, Noriaki Yokogawa, Takeshi Sasagawa, Hiroaki Nakashima, Naoki Segi, Sadayuki Ito, Toru Funayama, Fumihiko Eto, Akihiro Yamaji, Kota Watanabe, Satoshi Nori, Kazuki Takeda, Takeo Furuya, Atsushi Yunde, Hideaki Nakajima, Tomohiro Yamada, Tomohiko Hasegawa, Hidenori Suzuki, Yasuaki Imajo, Shota Ikegami, Masashi Uehara, Hitoshi Tonomura, Munehiro Sakata, Ko Hashimoto, Yoshito Onoda, Kenichi Kawaguchi, Yohei Haruta, Nobuyuki Suzuki, Kenji Kato, Hiroshi Uei, Hirokatsu Sawada, Kazuo Nakanishi, Kosuke Misaki, Hidetomi Terai, Koji Tamai, Akiyoshi Kuroda, Gen Inoue, Kenichiro Kakutani, Yuji Kakiuchi, Katsuhito Kiyasu, Hiroyuki Tominaga, Hiroto Tokumoto, Yoichi Iizuka, Eiji Takasawa, Koji Akeda, Norihiko Takegami, Haruki Funao, Yasushi Oshima, Takashi Kaito, Daisuke Sakai, Toshitaka Yoshii, Tetsuro Ohba, Bungo Otsuki, Shoji Seki, Masashi Miyazaki, Masayuki Ishihara, Seiji Okada, Shiro Imagama, Satoshi Kato

European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 32 ( 10 ) 3522 - 3532 2023年06月 [国際誌]

PURPOSE: To investigate the impact of early post-injury respiratory dysfunction for neurological and ambulatory ability recovery in patients with cervical spinal cord injury (SCI) and/or fractures. METHODS: We included 1,353 elderly patients with SCI and/or fractures from 78 institutions in Japan. Patients who required early tracheostomy and ventilator management and those who developed respiratory complications were included in the respiratory dysfunction group, which was further classified into mild and severe respiratory groups based on respiratory weaning management. Patient characteristics, laboratory data, neurological impairment scale scores, complications at injury, and surgical treatment were evaluated. We performed a propensity score-matched analysis to compare neurological outcomes and mobility between groups. RESULTS: Overall, 104 patients (7.8%) had impaired respiratory function. In propensity score-matched analysis, the respiratory dysfunction group had a lower home discharge and ambulation rates (p = 0.018, p = 0.001, respectively), and higher rate of severe paralysis (p < 0.001) at discharge. At the final follow-up, the respiratory dysfunction group had a lower ambulation rate (p = 0.004) and higher rate of severe paralysis (p < 0.001). Twenty-six patients with severe disability required respiratory management for up to 6 months post-injury and died of respiratory complications. The mild and severe respiratory dysfunction groups had a high percentage of severe paraplegic cases with low ambulatory ability; there was no significant difference between them. The severe respiratory dysfunction group tended to have a poorer prognosis. CONCLUSION: Respiratory dysfunction in elderly patients with SCI and/or cervical fracture in the early post-injury period reflects the severity of the condition and may be a useful prognostic predictor.

肝がん患者のSSI発生に関連する要因の検討

石貫智裕, 合田恵理香, 巽博臣, 加藤透, 原田敬介, 升田好樹, 大西浩文, 秦史壯, 大柳俊夫, 水口徹

日本外科系連合学会誌 ( 日本外科系連合学会 ) 48 ( 3 ) 409 - 409 2023年05月

肝がん患者のSSI発生に関連する要因の検討

石貫智裕, 合田恵理香, 巽博臣, 加藤透, 原田敬介, 升田好樹, 大西浩文, 秦史壯, 大柳俊夫, 水口徹

日本外科系連合学会誌 ( 日本外科系連合学会 ) 48 ( 3 ) 409 - 409 2023年05月

代謝異常関連脂肪肝疾患(MAFLD)は収縮期血圧の経時的な上昇と関連する線形混合効果モデルを用いた解析

遠藤圭佑, 森和真, 田中希尚, 佐藤達也, 大西浩文, 塙なぎさ, 古橋眞人

糖尿病 ( (一社)日本糖尿病学会 ) 66 ( Suppl.1 ) S - 264 2023年04月

Characterization of prehospital time delay in primary percutaneous coronary intervention for acute myocardial infarction: analysis of geographical infrastructure-dependent and -independent components.

Keisuke Oyatani, Masayuki Koyama, Nobuaki Himuro, Tetsuji Miura, Hirofumi Ohnishi

International journal of health geographics 22 ( 1 ) 7 - 7 2023年03月 [国際誌]

BACKGROUND: Prehospital delay in reaching a percutaneous coronary intervention (PCI) facility is a major problem preventing early coronary reperfusion in patients with ST-elevation myocardial infarction (STEMI). The aim of this study was to identify modifiable factors that contribute to the interval from symptom onset to arrival at a PCI-capable center with a focus on geographical infrastructure-dependent and -independent factors. METHODS: We analyzed data from 603 STEMI patients who received primary PCI within 12 h of symptom onset in the Hokkaido Acute Coronary Care Survey. We defined onset-to-door time (ODT) as the interval from the onset of symptoms to arrival at the PCI facility and we defined door-to-balloon time (DBT) as the interval from arrival at the PCI facility to PCI. We analyzed the characteristics and factors of each time interval by type of transportation to PCI facilities. In addition, we used geographical information system software to calculate the minimum prehospital system time (min-PST), which represents the time required to reach a PCI facility based on geographical factors. We then subtracted min-PST from ODT to find the estimated delay-in-arrival-to-door (eDAD), which represents the time required to reach a PCI facility independent of geographical factors. We investigated the factors related to the prolongation of eDAD. RESULTS: DBT (median [IQR]: 63 [44, 90] min) was shorter than ODT (median [IQR]: 104 [56, 204] min) regardless of the type of transportation. However, ODT was more than 120 min in 44% of the patients. The min-PST (median [IQR]: 3.7 [2.2, 12.0] min) varied widely among patients, with a maximum of 156 min. Prolongation of eDAD (median [IQR]: 89.1 [49, 180] min) was associated with older age, absence of a witness, onset at night, no emergency medical services (EMS) call, and transfer via a non-PCI facility. If eDAD was zero, ODT was projected to be less than 120 min in more than 90% of the patients. CONCLUSIONS: The contribution of geographical infrastructure-dependent time in prehospital delay was substantially smaller than that of geographical infrastructure-independent time. Intervention to shorten eDAD by focusing on factors such as older age, absence of a witness, onset at night, no EMS call, and transfer via a non-PCI facility appears to be an important strategy for reducing ODT in STEMI patients. Additionally, eDAD may be useful for evaluating the quality of STEMI patient transport in areas with different geographical conditions.

集中治療後の身体的・精神的介入におけるエビデンスに関する報告

水口徹, 石貫智裕, 野口美花, 間山明子, 和泉美保, 原田敬介, 巽博臣, 加藤透, 大柳俊夫, 大西浩文, 成松英智, 升田好樹

日本腹部救急医学会雑誌 ( (一社)日本腹部救急医学会 ) 43 ( 2 ) 575 - 575 2023年02月

Thyroid-stimulating hormone高値は男性の新規CKD発症と関連する

遠藤圭佑, 田中希尚, 佐藤達也, 塙なぎさ, 大西浩文, 古橋眞人

日本内科学会雑誌 ( (一社)日本内科学会 ) 112 ( 臨増 ) 176 - 176 2023年02月

Metabolic dysfunction-associated fatty liver disease is associated with an increase in systolic blood pressure over time: linear mixed-effects model analyses

Kazuma Mori, Marenao Tanaka, Itaru Hosaka, Takuma Mikami, Keisuke Endo, Nagisa Hanawa, Hirofumi Ohnishi, Masato Furuhashi

Hypertension Research ( Springer Science and Business Media LLC ) 2023年01月

Clinical impact of rehabilitation and <scp>ICU</scp> diary on critically ill patients: A systematic review and meta‐analysis

Tomohiro Ishinuki, Ling Zhang, Keisuke Harada, Hiroomi Tatsumi, Nobuaki Kokubu, Yoshika Kuno, Kanon Kumasaka, Rina Koike, Toshio Ohyanagi, Hirofumi Ohnishi, Eichi Narimatsu, Yoshiki Masuda, Toru Mizuguchi

Nursing in Critical Care ( Wiley ) 28 554 - 565 2023年01月 [査読有り] [国際誌]

Preserved Lower Limb Muscle Mass Prevents Insulin Resistance Development in Nondiabetic Older Adults.

Toshiaki Seko, Hiroshi Akasaka, Masayuki Koyama, Nobuaki Himuro, Shigeyuki Saitoh, Tetsuji Miura, Mitsuru Mori, Hirofumi Ohnishi

Journal of the American Medical Directors Association 24 ( 3 ) 376 - 381 2022年12月 [国際誌]

OBJECTIVE: To investigate roles of sarcopenia indexes in prediction of development of insulin resistance in nondiabetic older adults. DESIGN: A 2-year follow-up cohort. SETTING AND PARTICIPANTS: The Tanno-Sobetsu study, a prospective observational cohort, included 194 community-dwelling nondiabetic older adults during 2017-2019. METHODS: Lower limb, upper limb, appendicular, and trunk muscle masses by a bioelectrical impedance analysis, grip strength, knee extension torque, and walking speed were measured in study participants aged ≥65 years (79 men and 115 women) at baseline. Muscle mass and strength were divided by the weight, and then multiplied by 100 to calculate the weight ratio (%). Insulin resistance was assessed by homeostasis model (HOMA-IR) at baseline, and the study participants whose HOMA-IR was less than 1.73 at baseline were followed for a maximum of 2 years. The study endpoint was development of insulin resistance defined as HOMA-IR ≥1.73. The adjusted hazard ratio (HR) of each sarcopenia component for development of insulin resistance was calculated. RESULTS: Lower limb muscle mass (HR 0.88, 95% CI 0.79-0.98) and appendicular muscle mass (HR 0.89, 95% CI 0.81-0.99), but not other sarcopenia components, were associated with the development of insulin resistance, independently of sex and age, HOMA-IR, and waist circumference at baseline. CONCLUSIONS AND IMPLICATIONS: The loss of lower limb muscle mass is a significant risk factor for development of insulin resistance independently of obesity in nondiabetic older adults. The lower limb muscle mass may be a novel target of interventions for the prevention of diabetes in older adults.

オンラインPRO情報システムによる周術期における乳がん患者の不安に関連する要因の検証

石貫智裕, 水口徹, 九冨五郎, 島宏彰, 和田朝香, 里見蕗乃, 空閑陽子, 宇野智子, 久野芳佳, 浅石和昭, 下川原出, 増岡秀次, 三神俊彦, 大村東生, 本間敏男, 大西浩文, 大柳俊夫

北海道外科雑誌 ( 北海道外科学会 ) 67 ( 2 ) 161 - 161 2022年12月

尿酸とCOVID-19の原因ウイルスSARS-CoV-2の宿主側受容体ACE2との関連についての検討

古橋眞人, 田中希尚, 東浦幸村, 森和真, 小山雅之, 大西浩文, 齋藤重幸, 島本和明

痛風と尿酸・核酸 ( (一社)日本痛風・尿酸核酸学会 ) 46 ( 2 ) 160 - 160 2022年12月

血清尿酸値は女性において収縮期血圧の経時的な上昇と関連する線形混合効果モデルでの解析

森和真, 田中希尚, 東浦幸村, 小山雅之, 塙なぎさ, 大西浩文, 古橋眞人

痛風と尿酸・核酸 ( (一社)日本痛風・尿酸核酸学会 ) 46 ( 2 ) 166 - 166 2022年12月

A Biomechanical Comparison of 2 Over-the-Top Anterior Cruciate Ligament Reconstruction Techniques: A Cadaveric Study Using a Robotic Simulator.

Kousuke Shiwaku, Tomoyuki Suzuki, Konsei Shino, Satoshi Yamakawa, Hidenori Otsubo, Shinichiro Okimura, Daisuke Suzuki, Shogo Nabeki, Atsushi Teramoto, Hirofumi Ohnishi, Hiromichi Fujie, Toshihiko Yamashita

Orthopaedic journal of sports medicine 10 ( 12 ) 23259671221139876 - 23259671221139876 2022年12月 [国際誌]

BACKGROUND: For skeletally immature patients, over-the-top (OTT) anterior cruciate ligament (ACL) reconstruction (ACLR) is preferred. However, increased anterior laxity at deep knee flexion angles remains concerning. We modified the procedure to proximally shift the graft fixation site on the femur to prevent graft loosening at higher knee flexion angles and named it the supra-OTT procedure. PURPOSE: To compare anterior laxity and in situ forces of the ACL graft between conventional OTT and supra-OTT ACLR in a cadaveric model. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 11 fresh-frozen cadaveric knee specimens underwent 4 robotic testing conditions: ACL intact, ACL resected, conventional OTT, and supra-OTT. For each condition, a 100-N load was applied at 0°, 15°, 30°, 60°, and 90° of knee flexion to simulate the Lachman test or anterior drawer test. In addition, a combined load of 5-N·m internal tibial torque and 10-N·m valgus torque was applied at 15° and 30° of knee flexion as a simulated pivot-shift test. Anterior tibial translation and in situ graft forces were recorded. The only difference between conventional OTT and supra-OTT ACLR was the graft fixation site on the femur. For conventional OTT ACLR, graft fixation was performed just on the proximal and lateral ends of the posterior condyle. For supra-OTT ACLR, the fixation point was around the proximal insertion of the lateral head of the gastrocnemius and the lateral edge of the posterior cortex, approximately 2 cm proximal to the conventional OTT position. RESULTS: On the simulated anterior drawer test at 60° and 90° of knee flexion, anterior tibial translation after supra-OTT ACLR was significantly smaller than after conventional OTT ACLR (P < .01). However, no significant differences were noted at other flexion angles or on the simulated pivot-shift test between the conventional OTT and supra-OTT procedures. Some overconstraint and higher graft forces were noted with both techniques, but the supra-OTT technique caused even more overconstraint at higher flexion angles. CONCLUSION: Supra-OTT ACLR showed better biomechanical performance to control anterior laxity than conventional OTT ACLR at higher knee flexion angles. CLINICAL RELEVANCE: The supra-OTT procedure may improve anterior stability at deep knee flexion angles.

Walking Speed Is Better Than Hand Grip Strength as an Indicator of Early Decline in Physical Function with Age in Japanese Women Over 65: A Longitudinal Analysis of the Tanno-Sobetsu Study Using Linear Mixed-Effects Models.

Shunichi Ogawa, Nobuaki Himuro, Masayuki Koyama, Toshiaki Seko, Mitsuru Mori, Hirofumi Ohnishi

International journal of environmental research and public health 19 ( 23 ) 2022年11月 [国際誌]

The decline in physical function with age is a major contributor to the need for long-term care. Age-related changes in hand grip strength, knee extension, and walking speed have been reported in cross-sectional studies, but longitudinal data are needed. This longitudinal study measured changes in these three measures among community-dwelling adults aged 65-89 years who participated in general health examinations between 2017 and 2019. Analyses were stratified by sex. Linear mixed-effects models adjusted for confounding factors were used to examine the interaction of different patterns of change with age of the three measures. A total of 284 participants were included in the analysis. The interaction term of age × walking speed, with age × handgrip strength as the reference, was statistically significant in women and showed different patterns in walking speed and hand grip strength. In men, none of the age × physical function interaction terms were significant in any model. For early recognition of the onset of physical function decline in older adults, any of the three measures may be used in men, but walking speed may be more suitable than hand grip strength in women. These findings may be useful in devising sex-specific screening strategies.

Correction: Toe grip strength declines earlier than hand grip strength and knee extension strength in community‑dwelling older men: a cross sectional study.

Sayo Miura, Toshiaki Seko, Nobuaki Himuro, Masayuki Koyama, Shigeyuki Saitoh, Hirofumi Ohnishi

Journal of foot and ankle research 15 ( 1 ) 81 - 81 2022年11月 [国際誌]

The Role of the Medial Meniscus in Anterior Knee Stability.

Kousuke Shiwaku, Tomoaki Kamiya, Daisuke Suzuki, Satoshi Yamakawa, Hidenori Otsubo, Tomoyuki Suzuki, Katsunori Takahashi, Yohei Okada, Atsushi Teramoto, Hirofumi Ohnishi, Hiromichi Fujie, Toshihiko Yamashita

Orthopaedic journal of sports medicine 10 ( 11 ) 23259671221132845 - 23259671221132845 2022年11月 [国際誌]

Background: Few studies have compared the force distribution between the anterolateral, posterolateral, and medial structures of the knee. Purpose: To investigate the important structures in an intact knee contributing to force distribution in response to anterior tibial load. Study Design: Controlled laboratory study. Methods: Nine fresh-frozen cadaveric knee specimens underwent robotic testing. First, 100 N of anterior tibial load was applied to the intact knee at 0°, 15°, 30°, 60°, and 90° of knee flexion. The anterior cruciate ligament (ACL), anterolateral capsule, lateral collateral ligament, popliteal tendon, posterior root of the lateral meniscus, superficial medial collateral ligament, posterior root of the medial meniscus (MM), and posterior cruciate ligament were then completely transected in sequential order. After each transection, the authors reproduced the intact knee motion when a 100-N anterior tibial load was applied. By applying the principle of superposition, the resultant force of each structure was determined based on the 6 degrees of freedom force/torque data of each state. Results: At every measured knee flexion angle, the resultant force of the ACL was the largest of the tested structures. At knee flexion angles of 60° and 90°, the resultant force of the MM was larger than that of all other structures with the exception of the ACL. Conclusion: The MM was identified as playing an important role in response to anterior tibial load at 60° and 90° of flexion. Clinical Relevance: In clinical settings, the ACL of patients with a poorly functioning MM, such as tear of the MM posterior root, should be monitored considering the large resultant force in response to an anterior tibial load.

新型コロナウイルス感染症の自宅療養者に対する健康観察アプリケーションのユーザビリティ

中山龍一, 小山雅之, 高塚伸太朗, 向原強, 谷川琢海, 藤本直樹, 福田潤, 小澤秀弘, 大西浩文, 上村修二

医療情報学連合大会論文集 ( (一社)日本医療情報学会 ) 42回 539 - 541 2022年11月

新型コロナウイルス感染症の自宅療養者に対する健康観察アプリケーションのユーザビリティ

中山龍一, 小山雅之, 高塚伸太朗, 向原強, 谷川琢海, 藤本直樹, 福田潤, 小澤秀弘, 大西浩文, 上村修二

医療情報学連合大会論文集 ( (一社)日本医療情報学会 ) 42回 539 - 541 2022年11月

官学連携により産まれたCOVID-19健康観察システム「こびまるライト」

小山雅之, 谷川琢海, 高塚伸太朗, 中山龍一, 向原強, 藤本直樹, 福田潤, 齋藤彩乃, 石川珠美, 小澤秀弘, 大西浩文

医療情報学連合大会論文集 ( (一社)日本医療情報学会 ) 42回 545 - 546 2022年11月

官学連携により産まれたCOVID-19健康観察システム「こびまるライト」

小山雅之, 谷川琢海, 高塚伸太朗, 中山龍一, 向原強, 藤本直樹, 福田潤, 齋藤彩乃, 石川珠美, 小澤秀弘, 大西浩文

医療情報学連合大会論文集 ( (一社)日本医療情報学会 ) 42回 545 - 546 2022年11月

Toe Grip strength declines earlier than hand grip strength and knee extension strength in community-dwelling older men: a cross sectional study.

Sayo Miura, Toshiaki Seko, Nobuaki Himuro, Masayuki Koyama, Shigeyuki Saitoh, Hirofumi Ohnishi

Journal of foot and ankle research 15 ( 1 ) 79 - 79 2022年10月 [国際誌]

BACKGROUND: The aim of this study is to examine the age-related changes in the toe grip strength and its differences from hand grip strength and knee extension strength using cross-sectional data. METHODS: Of participants aged 65 years over who underwent health checkups for lifestyle-related diseases in 2018, 307 men and women met the criteria. Toe grip strength, hand grip strength, and knee extension strength were also measured as optional tests. The participants were divided into five groups categorized by every 5 years of age (Group 65-85). The data were analyzed with multiple comparisons using the linear mixed multilevel model to examine the following categories: association between age and muscle strength, differences in the pattern of change, and gender, using the 65-69 years group as a reference. RESULTS: In men, there were interaction effects between the factors of age and muscle, but in women there were not. Toe grip strength was significantly lower in Group 70, 75, 80, and 85 in men, lower in Group 85 than in 65 in women. Hand grip strength was significantly lower in Group 85 than in 65 in both men and women. There was no significant difference in knee extension strength among the age groups for both men and women. CONCLUSIONS: The decline in toe grip strength may occur earlier and in a different pattern from hand grip strength and knee extension strength in men.

Deep learning algorithm to detect fibrosing interstitial lung disease on chest radiographs.

Hirotaka Nishikiori, Koji Kuronuma, Kenichi Hirota, Naoya Yama, Tomohiro Suzuki, Maki Onodera, Koichi Onodera, Kimiyuki Ikeda, Yuki Mori, Yuichiro Asai, Yuzo Takagi, Seiwa Honda, Hirofumi Ohnishi, Masamitsu Hatakenaka, Hiroki Takahashi, Hirofumi Chiba

The European respiratory journal 61 ( 2 ) 2022年10月 [国際誌]

BACKGROUND: Antifibrotic therapies are available to treat chronic fibrosing interstitial lung diseases (CF-ILDs), including idiopathic pulmonary fibrosis. Early use of these treatments is recommended to slow deterioration of respiratory function and to prevent acute exacerbation. However, identifying patients in the early stages of CF-ILD using chest radiographs (CRs) is challenging. In this study, we developed and tested a deep learning algorithm to detect CF-ILD using CR images. METHOD: From the image archive of Sapporo Medical University Hospital, 653 CRs from 263 patients with CF-ILDs and 506 from 506 patients without CF-ILD were identified; 921 were used for deep learning and 238 were used for algorithm testing. The algorithm was designed to output a numerical score ranging from 0 to 1, representing the probability of CF-ILD. Using the testing dataset, the algorithm's capability to identify CF-ILD was compared with that of doctors. A second dataset, in which CF-ILD was confirmed using computed tomography images, was used to further evaluate the algorithm's performance. RESULTS: The area under the curve of the receiver operating characteristic curve, which indicates the algorithm's detection capability, was 0.979. Using a score cutoff of 0.267, the sensitivity and specificity of detection were 0.896 and 1.000, respectively. These data showed that the algorithm's performance was non-inferior to that of doctors, including pulmonologists and radiologists; performance was verified using the second dataset. CONCLUSIONS: We developed a deep learning algorithm to detect CF-ILDs using CR images. The algorithm's detection capability was non-inferior to that of doctors.

オンラインPRO情報システムによる乳がん患者の精神状態と生活の質変化に関する研究

石貫智裕, 九冨五郎, 沖田憲司, 島宏彰, 和田朝香, 青木武士, 吉田寛, 渡邉学, 横尾英樹, 問山裕二, 大西浩文, 大柳俊夫, 水口徹

日本癌治療学会学術集会(Web) ( (一社)日本癌治療学会 ) 60回 P63 - 5 2022年10月

オンラインPRO情報システムによる乳がん患者の精神状態と生活の質変化に関する研究

石貫智裕, 九冨五郎, 沖田憲司, 島宏彰, 和田朝香, 青木武士, 吉田寛, 渡邉学, 横尾英樹, 問山裕二, 大西浩文, 大柳俊夫, 水口徹

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 ) 60回 P63 - 5 2022年10月

児童生徒が主体的に取り組む感染症予防対策の実践活動ありがとうプロジェクトの進捗報告(第2報)

大浦麻絵, 大西浩文, 小山雅之, 長多好恵, 長谷川準子, 助友裕子, 森満

北海道公衆衛生学雑誌 ( 北海道公衆衛生学会 ) 36 ( 1特別付録 ) 55 - 55 2022年10月

Fatty liver index(FLI)の高値は虚血性心疾患の独立した予測因子である

森和真, 田中希尚, 東浦幸村, 塙なぎさ, 大西浩文, 古橋眞人

日本高血圧学会総会プログラム・抄録集 ( (NPO)日本高血圧学会 ) 44回 60 - 60 2022年10月

Fatty liver index(FLI)の高値は虚血性心疾患の独立した予測因子である

森和真, 田中希尚, 東浦幸村, 塙なぎさ, 大西浩文, 古橋眞人

日本高血圧学会総会プログラム・抄録集 ( (NPO)日本高血圧学会 ) 44回 60 - 60 2022年10月

水口徹, 石貫智裕, 張苓, 巽博臣, 久野芳佳, 原田敬介, 大西浩文, 加藤透, 沖田憲司, 川本雅樹, 永山稔, 竹政伊知朗, 大柳俊夫

日本外科感染症学会雑誌 ( (一社)日本外科感染症学会 ) 19 ( 1 ) 230 - 230 2022年10月

一次縫合創に対するNPWTの最適な適応とは SSI予防ガイドラインの次期改定に必要な予防的NPWTに関する有効性の再考

水口徹, 石貫智裕, 張苓, 巽博臣, 久野芳佳, 原田敬介, 大西浩文, 加藤透, 沖田憲司, 川本雅樹, 目黒誠, 秦史壯, 大柳俊夫

日本外科感染症学会雑誌 ( (一社)日本外科感染症学会 ) 19 ( 1 ) 185 - 185 2022年10月

Risk Factors for Early Childhood Caries in Three-Year-Old Japanese Children: A Prospective Cohort Study.

Yoshimi Nakayama, Hirofumi Ohnishi

Pediatric dentistry 44 ( 5 ) 346 - 354 2022年09月 [国際誌]

Purpose: he purpose of this study was to examine risk factors in the development of early childhood caries (ECC) at age three years in a prospective cohort study of 18- to 23-month-old children. Methods: This was a longitudinal observational study of 872 children 18 to 23 months of age in Hokkaido, Japan, with follow-up at age three years. A self-administered questionnaire was completed by parents or guardians of the children. The baseline survey contents included sex, age, the existence of smokers in the home, maternal smoking during pregnancy, nocturnal breastfeeding, snacking habits, bottle-feeding, frequency of parents brushing their child's teeth, the use of fluoride toothpaste, parents sharing of utensils with child, and socio-economic status. The number of decayed, missing, or filled teeth (dmft) was obtained from dental examinations in both the baseline and follow-up surveys. Logistic regression analysis was performed to estimate the odds ratio for the new onset of ECC in threeyear-olds. Results: The dmft at 18 to 23 months old, nocturnal breastfeeding, prolonged breastfeeding, snacking habits, parents brushing their child's teeth less frequently, and parental sharing utensils with the child were significantly associated with the incidence of ECC at age three years. Conclusions: The existence of early childhood caries in 18- to 23-month-olds may be a strong predictor of the new development of dental caries. Other lifestyles were found to be risk factors for the incidence of dental caries by age three years.

Prognostic Factors for Respiratory Dysfunction for Cervical Spinal Cord Injury and/or Cervical Fractures in Elderly Patients: A Multicenter Survey.

Ryosuke Hirota, Yoshinori Terashima, Hirofumi Ohnishi, Toshihiko Yamashita, Noriaki Yokogawa, Takeshi Sasagawa, Kei Ando, Hiroaki Nakashima, Naoki Segi, Toru Funayama, Fumihiko Eto, Akihiro Yamaji, Kota Watanabe, Junichi Yamane, Kazuki Takeda, Takeo Furuya, Atsushi Yunde, Hideaki Nakajima, Tomohiro Yamada, Tomohiko Hasegawa, Hidenori Suzuki, Yasuaki Imajo, Shota Ikegami, Masashi Uehara, Hitoshi Tonomura, Munehiro Sakata, Ko Hashimoto, Yoshito Onoda, Kenichi Kawaguchi, Yohei Haruta, Nobuyuki Suzuki, Kenji Kato, Hiroshi Uei, Hirokatsu Sawada, Kazuo Nakanishi, Kosuke Misaki, Hidetomi Terai, Koji Tamai, Eiki Shirasawa, Gen Inoue, Kenichiro Kakutani, Yuji Kakiuchi, Katsuhito Kiyasu, Hiroyuki Tominaga, Hiroto Tokumoto, Yoichi Iizuka, Eiji Takasawa, Koji Akeda, Norihiko Takegami, Haruki Funao, Yasushi Oshima, Takashi Kaito, Daisuke Sakai, Toshitaka Yoshii, Tetsuro Ohba, Bungo Otsuki, Shoji Seki, Masashi Miyazaki, Masayuki Ishihara, Seiji Okada, Shiro Imagama, Satoshi Kato

Global spine journal 21925682221095470 - 21925682221095470 2022年05月 [国際誌]

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVE: The purpose of this study was to investigate the prognosis of respiratory function in elderly patients with cervical spinal cord injury (SCI) and to identify predictive factors. METHODS: We included 1353 cases of elderly cervical SCI patients collected from 78 institutions in Japan. Patients who required early tracheostomy and ventilator management and those who developed respiratory complications were defined as the respiratory disability group. Patients' background characteristics, injury mechanism, injury form, neurological disability, complications, and treatment methods were compared between the disability and non-disability groups. Multiple logistic regression analysis was used to examine the independent factors. Patients who required respiratory management for 6 months or longer after injury and those who died of respiratory complications were classified into the severe disability group and were compared with minor cases who were weaned off the respirator. RESULTS: A total of 104 patients (7.8%) had impaired respiratory function. Comparisons between the disabled and non-disabled groups and between the severe and mild injury groups yielded distinct trends. In multiple logistic regression analysis, age, blood glucose level, presence of ossification of posterior longitudinal ligament (OPLL), anterior vertebral hematoma, and critical paralysis were selected as independent risk factors. CONCLUSION: Age, OPLL, severe paralysis, anterior vertebral hematoma, hypoalbuminemia, and blood glucose level at the time of injury were independent factors for respiratory failure. Hyperglycemia may have a negative effect on respiratory function in this condition.

Metabolic dysfunction-associated fatty liver disease predicts new onset of chronic kidney disease better than does fatty liver or nonalcoholic fatty liver disease.

Marenao Tanaka, Kazuma Mori, Satoko Takahashi, Yukimura Higashiura, Hirofumi Ohnishi, Nagisa Hanawa, Masato Furuhashi

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 2022年05月 [国際誌]

BACKGROUND: Possible associations of chronic kidney disease (CKD) with fatty liver (FL) and nonalcoholic fatty liver disease (NAFLD) have recently been focused on. Metabolic dysfunction-associated fatty liver disease (MAFLD), defined as FL with overweight/obesity, type 2 diabetes mellitus or metabolic abnormalities, has been proposed as a new feature of chronic liver disease. However, the relationship between MAFLD and new onset of CKD has not been fully addressed. METHODS: We investigated the associations of FL, NAFLD and MAFLD with the development of CKD, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2 or positive for urinary protein, over a 10-year period in 28 890 Japanese subjects who received annual health examinations. After exclusion of subjects with no data for abdominal ultrasonography and subjects with CKD at baseline, a total of 13 159 subjects (men/women: 8581/4578, mean age: 48 years) were recruited. RESULTS: The prevalences of FL, NAFLD and MAFLD were 34.6% (men/women: 45.1%/15.1%), 32.8% (men/women: 42.7%/14.5%) and 32.3% (men/women: 42.4%/13.4%), respectively. During the 10-year follow-up period, 2163 subjects (men/women: 1475/688) had new onset of CKD. Multivariable Cox proportional hazard model analyses showed that MAFLD (hazard ratio [95% confidence interval]: 1.12 [1.02-1.26], p = 0.027), but not FL or NAFLD, was an independent risk factor for new onset of CKD after adjustment of age, sex, eGFR, current smoking habit, ischemic heart disease, diabetes mellitus, overweight/obesity, hypertension and dyslipidemia. The addition of MAFLD (continuous net reclassification improvement [NRI]: 0.154, integrated discrimination improvement [IDI]: 0.0024) to traditional risk factors without metabolic abnormalities significantly improved the discriminatory capacity better than did the addition of FL (NRI: 0.138, IDI: 0.0018) or NAFLD (NRI: 0.132, IDI: 0.0017). CONCLUSIONS: MAFLD is modestly and independently associated with new onset of CKD and predicts the risk for development of CKD better than does FL or NAFLD.

Fatty liver index(FLI)の高値は虚血性心疾患の独立した予測因子である。

森和真, 森和真, 田中希尚, 東浦幸村, 塙なぎさ, 大西浩文, 大西浩文, 古橋眞人

日本高血圧学会総会プログラム・抄録集(CD-ROM) 52 ( 8 ) 687 - 698 2022年05月 [国際誌]

AIM: Fatty liver index (FLI), which is calculated by using body mass index, waist circumference and levels of γ-glutamyl transferase and triglycerides, is a validated surrogate marker of nonalcoholic fatty liver disease. We retrospectively investigated the relationship between FLI and the development of ischemic heart disease (IHD) during a 10-year period. METHODS: Among subjects who received annual health checkups (n = 28 990), a total of 18 851 subjects (men/women: 11 659/7192) were enrolled after exclusion of subjects with missing data and those with IHD at baseline. RESULTS: FLI at baseline was significantly higher in men than in women. During the 10-year period, 450 men (3.9%) and 123 women (1.7%) had new onset of IHD determined by a self-reported questionnaire survey. Multivariable Cox proportional hazard models with a restricted cubic spline showed that hazard risk (HR) for the development of IHD increased with a higher FLI at baseline after adjustment of age, sex, current smoking habit, family history of IHD and diagnosis of diabetes mellitus, hypertension, dyslipidemia and chronic kidney disease at baseline. There was no significant interaction between FLI and sex for the adjusted HR. When divided by tertiles of FLI at baseline (T1∼T3), the adjusted risk for development of IHD in the T3 group (HR [95% confidence interval]: 1.34 [1.05-1.71]) was significantly higher than that in the T1 group as the reference. The addition of FLI into traditional risk factors for IHD significantly improved the discriminatory capability. CONCLUSIONS: A high level of FLI is an independent predictor of new onset of IHD during a 10-year period.

DOI PubMed J-GLOBAL

Circulating level of fatty acid-binding protein 4 is an independent predictor of metabolic dysfunction-associated fatty liver disease in middle-aged and elderly individuals.

Marenao Tanaka, Satoko Takahashi, Yukimura Higashiura, Akiko Sakai, Masayuki Koyama, Shigeyuki Saitoh, Kazuaki Shimamoto, Hirofumi Ohnishi, Masato Furuhashi

Journal of diabetes investigation 13 ( 5 ) 878 - 888 2022年05月 [国内誌]

AIMS/INTRODUCTION: Metabolic dysfunction-associated fatty liver disease (MAFLD), defined as hepatosteatosis with type 2 diabetes mellitus, overweight/obesity or metabolic dysregulation, has been proposed as a new feature of chronic liver disease. Fatty acid-binding protein 4 (FABP4) is expressed in adipose tissue, and secreted FABP4 is associated with the development of insulin resistance and atherosclerosis. However, the relationship between MAFLD and FABP4 has not been fully addressed. MATERIALS AND METHODS: Associations of MAFLD with metabolic markers, including FABP4, fibroblast growth factor 21 and adiponectin, were investigated in 627 individuals (men/women 292/335) in the Tanno-Sobetsu Study, a population-based cohort. RESULTS: The mean age was 65 years (range 19-98 years, median [interquartile range] 68 [56-76] years). Hepatosteatosis was determined by the fatty liver index (FLI), and FLI ≥35 for men and FLI ≥16 for women were used for detection of fatty liver, as previously reported using 14,471 Japanese individuals. FLI was positively correlated with systolic blood pressure and levels of FABP4 (r = 0.331, P < 0.001), fibroblast growth factor 21, homeostasis model assessment of insulin resistance as an insulin resistance index and uric acid, and was negatively correlated with levels of high-density lipoprotein cholesterol and adiponectin. FABP4 concentration was independently associated with FLI after adjustment of age, sex, systolic blood pressure and levels of uric acid, high-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21 in multivariable regression analysis. Logistic regression analysis showed that FABP4 was an independent predictor of MAFLD after adjustment of age, sex, presence of diabetes mellitus, hypertension and dyslipidemia, and levels of uric acid, homeostasis model assessment of insulin resistance, adiponectin and fibroblast growth factor 21. CONCLUSIONS: FABP4 concentration is independently associated with FLI and is an independent predictor of MAFLD in middle-aged and elderly individuals.

代謝異常関連脂肪肝疾患(MAFLD)とCKD発症リスクの関連についての検討

田中希尚, 高橋聖子, 森和真, 東浦幸村, 大西浩文, 塙なぎさ, 古橋眞人

日本腎臓学会誌 ( (一社)日本腎臓学会 ) 64 ( 3 ) 223 - 223 2022年05月

代謝異常関連脂肪肝疾患(MAFLD)とCKD発症リスクの関連についての検討

田中希尚, 高橋聖子, 森和真, 東浦幸村, 大西浩文, 塙なぎさ, 古橋眞人

日本腎臓学会誌 ( (一社)日本腎臓学会 ) 64 ( 3 ) 223 - 223 2022年05月

Increased LDL cholesterol level is associated with deterioration of renal function in males

Arata Osanami, Marenao Tanaka, Masato Furuhashi, Hirofumi Ohnishi, Nagisa Hanawa, Tomohisa Yamashita, Norihito Moniwa, Tetsuji Miura

Clinical Kidney Journal ( Oxford University Press (OUP) ) 15 ( 10 ) 1888 - 1895 2022年04月 [国際誌]

Abstract Background Relationships between levels of serum lipid fractions and the time course of renal function are discrepant in the literature. Here we examined this issue by analyses of healthy subjects in a cohort. Methods Of all subjects who received health examinations at Keijinkai Maruyama Clinic, Sapporo in 2006, subjects with hypertension, diabetes mellitus or chronic kidney disease (CKD) and those taking medication for dyslipidemia were excluded, and a total of 5,586 subjects (male/female: 3,563/2,023, mean age: 43 ± 8 years) were followed for 10 years. Results Linear mixed effect models showed that baseline low-density lipoprotein (LDL)-cholesterol level was negatively associated with estimated glomerular filtration rate (eGFR) during the 10-year follow-up period after adjustment of confounders. Interactions between the follow-up year and baseline level of LDL-cholesterol or high-density lipoprotein (HDL)-cholesterol for eGFR values during the follow-up period were significant in males but not in females. There were no significant interactions for eGFR between the follow-up year and baseline levels of total cholesterol, triglycerides, or HDL-cholesterol/triglycerides ratio. During the follow-up period, 346 males and 223 females developed CKD. When male subjects were divided into subgroups according to tertiles of baseline levels of LDL-cholesterol, the adjusted risk for CKD in the third tertial group was significantly higher than that in the first tertile group as a reference (hazard ratio [95% confidence interval]: 1.39 [1.02-1.90], p = 0.035). Such a difference was not observed for LDL-cholesterol tertiles in females or HDL-cholesterol tertiles in both sexes. Conclusions A high LDL-cholesterol level may be a risk factor of new-onset CKD in apparently healthy males.

Prediction and validation of nonalcoholic fatty liver disease by fatty liver index in a Japanese population.

Satoko Takahashi, Marenao Tanaka, Yukimura Higashiura, Kazuma Mori, Nagisa Hanawa, Hirofumi Ohnishi, Masato Furuhashi

Endocrine journal 69 ( 4 ) 463 - 471 2022年04月 [国内誌]

Fatty liver index (FLI) calculated by using body mass index (BMI), waist circumference and levels of γ-glutamyl transferase and triglycerides is a non-invasive predictor of nonalcoholic fatty liver disease (NAFLD). The original study in Italy showed that the cutoff level for prediction of NAFLD was FLI ≥60. However, the sex difference in FLI was not taken into consideration, and it is unclear whether the cutoff value can be applied to other races. We investigated the cutoff value of FLI for prediction of NAFLD determined by abdominal ultrasonography using receiver operating characteristic curve analyses in 14,471 Japanese subjects (men/women: 9,240/5,231; mean age: 48 ± 9 years). There was a significant interaction between sex and FLI for detection of NAFLD (p < 0.001). The cutoff values of FLI in men and women were 35.1 (area under the curve [AUC]: 0.82) and 15.6 (AUC: 0.91), respectively. When the subjects were divided by the absence and presence of obesity (BMI ≥25), there was a significant interaction between FLI and obesity for detection of NAFLD in women (p < 0.001) but not in men (p = 0.679). The cutoff values of FLI in non-obese/obese men and women were 22.6/52.6 and 11.2/33.2, respectively. In conclusion, the cutoff value of FLI for prediction of NAFLD in Japanese individuals was lower than that in the original study, and there is a significant sex difference. The simple and useful cutoff values in Japanese men and women are FLI ≥35 (non-obese/obese: 23/53) and FLI ≥16 (non-obese/obese: 11/33), respectively.

High fibrosis-4 (FIB-4) index predicts new onset of ischemic heart disease during a 10-year period in a general population

Yukimura Higashiura, Marenao Tanaka, Kazuma Mori, Takuma Mikami, Itaru Hosaka, Hirofumi Ohnishi, Nagisa Hanawa, Masato Furuhashi

European Heart Journal Open ( Oxford University Press (OUP) ) 2 ( 3 ) oeac030 2022年04月 [国際誌]

Abstract Aims The fibrosis-4 (FIB-4) index, calculated by using age, platelet count and levels of aspartate aminotransferase and alanine aminotransferase, is a noninvasive indicator for detection of liver fibrosis. Advanced hepatic fibrosis is associated with morbidity and mortality in patients with nonalcoholic fatty liver disease. However, the relationship between liver fibrosis and the development of ischemic heart disease (IHD) has not fully been addressed. Methods and Results We investigated the association between FIB-4 index and new onset of IHD during a 10-year period in a general population of subjects who received annual health examinations (n = 28,990). After exclusion of subjects with missing data and those with a history of IHD at baseline, a total of 13,448 subjects (men/women: 8,774/4,674, mean age: 48 years) were included. During the 10-year period, 378 men (4.3%) and 77 women (1.6%) had new onset of IHD. Multivariable Cox proportional hazard models with a restricted cubic spline showed that hazard risk for the development of IHD increased with a higher FIB-4 index at baseline after adjustment of age, sex, fatty liver (FL) determined by ultrasonography, estimated glomerular filtration rate, habits of current smoking and alcohol drinking, family history of IHD, and diagnosis of hypertension, diabetes mellitus and dyslipidemia. When divided by FL, FIB-4 index was an independent predictor for the development of IHD in subjects with FL but not in those without FL. The addition of FIB-4 index to traditional risk factors for IHD significantly improved the discriminatory capability. Conclusion A high level of FIB-4 index predicts new onset of IHD during a 10-year period.

Effect of Early Surgical Intervention for Brain Tumors Associated with Epilepsy on the Improvement in Memory Performance.

Tsukasa Hirano, Hime Suzuki, Katsuya Komatsu, Aya Kanno, Yuusuke Kimura, Rei Enatsu, Satoko Ochi, Hirofumi Ohnishi, Nobuhiro Mikuni

Neurologia medico-chirurgica 62 ( 6 ) 286 - 293 2022年04月 [国内誌]

We evaluated the effect of early surgical intervention on the change in memory performance of patients with low-grade brain tumors associated with epilepsy. Twenty-three adult patients with low-grade brain tumors and epilepsy who underwent surgery at our institution between 2010 and 2019 were included. The Wechsler Memory Scale-Revised (WMS-R) was used to assess cognitive memory performance. Memory performance before and after surgery was retrospectively evaluated. In addition, the relationships among preoperative memory function, postoperative seizure outcome, preoperative seizure control, temporal lobe lesion, and change in memory function were examined. There were statistically significant improvements from median preoperative to postoperative WMS-R subscale scores for verbal memory, general memory, and delayed recall (p<0.001, p<0.001, and p=0.0055, respectively) regardless of preoperative sores and tumor location. Good postsurgical seizure control was associated with significant improvements in postoperative WMS-R performance. Our results indicated that early surgical intervention might improve postoperative memory function in patients with low-grade brain tumors and epilepsy.

Fibrosis-4(FIB-4)Indexは新規の虚血性心疾患発症の独立した予測因子である

東浦幸村, 古橋眞人, 田中希尚, 森和真, 高橋聖子, 大西浩文, 塙なぎさ

糖尿病 ( (一社)日本糖尿病学会 ) 65 ( Suppl.1 ) S - 187 2022年04月

新型コロナウイルス感染症（COVID-19）と健康リテラシー教育【総説】

大西浩文, 大浦麻絵, 小山雅之, 長多好恵, 長谷川準子, 助友裕子, 森満

北海道生命倫理研究 ( 北海道生命倫理研究会 ) 10 13 - 19 2022年03月

In Japanese medical issues, the use of terms “Western medicine” and “Eastern medicine” seem to divide the category “medicine” into two twin concepts, based on the area. However, it can be said that “Eastern/Oriental medicine” is given a greatly different definition―that of a derived context―whereas Western medicine is often given a coherent definition―“new medicine transmitted to Japan from the outside” through a historic process. Consequently, the term Oriental/Eastern medicine has been given a strong characteristic of the polysemic word.The term Western/Oriental medicine has been used by medical institutions in Japan. In this field, the background as a polysemic word has been shared, and the state that the treatment accepted various contexts has been maintained so far. Nevertheless, given its newer context,―Oriental/Eastern medicine―has spreads in recent years, and there is a tendency toward the use of the new definition, passing over the conventional polysemic word. It is possible that a discrepancy between the background and context of the conventional polysemic word may occur. There is also concern regarding the confusion around the meaning of the term Eastern/Oriental medicine.This paper intend to rearrange the transition of the relationship between the concepts under the historic context and the meaning of Eastern/Oriental medicine as a polysemic word.

Plasma Tsukushi Concentration Is Associated with High Levels of Insulin and FGF21 and Low Level of Total Cholesterol in a General Population without Medication.

Masato Furuhashi, Yukimura Higashiura, Akiko Sakai, Masayuki Koyama, Marenao Tanaka, Shigeyuki Saitoh, Kazuaki Shimamoto, Hirofumi Ohnishi

Metabolites 12 ( 3 ) 2022年03月 [国際誌]

Tsukushi (TSK) is a member of the small leucine-rich proteoglycan family that controls developmental processes and organogenesis. TSK was also identified as a new hepatokine, which is mainly expressed in the liver, and is secreted by hepatocytes, to regulate energy and glycolipid metabolism in response to nonalcoholic fatty liver disease. However, the role of plasma TSK, especially its role in the general population, has not been fully addressed. We investigated the associations between plasma TSK concentration and several metabolic markers, including fibroblast growth factor 21 (FGF21), a hepatokine, and adiponectin, an adipokine, in 253 subjects (men/women: 114/139) with no medication in the Tanno-Sobetsu Study, which employed a population-based cohort. There was no significant sex difference in plasma TSK concentration, and the level was positively correlated with the fatty liver index (FLI) (r = 0.131, p = 0.038), levels of insulin (r = 0.295, p < 0.001) and levels of FGF21 (r = 0.290, p < 0.001), and was negatively correlated with the total cholesterol level (r = -0.124, p = 0.049). There was no significant correlation between the TSK level and body mass index, waist circumference, adiponectin, high-density lipoprotein cholesterol or total bile acids. The multivariable regression analysis showed that high levels of insulin and FGF21 and a low level of total cholesterol were independent determinants of plasma TSK concentration, after adjustment for age, sex and FLI. In conclusion, plasma TSK concentration is independently associated with high levels of insulin and FGF21, a hepatokine, and a low level of total cholesterol, but not with adiposity and adiponectin, in a general population of subjects who have not taken any medications.

子ども達から市民に届ける感染症予防啓発活動コロナ禍における学校と連携した手洗い活動

大浦麻絵, 大西浩文, 助友裕子, 小山雅之, 長多好恵, 長谷川準子, 森満

札幌保健科学雑誌 ( 札幌医科大学保健医療学部 ) ( 11 ) 1 - 6 2022年03月

本稿においては,我々が地域における公衆衛生活動の一環として実施している「学童における感染症予防教育活動」を紹介する.本活動は2017年から開始され,地域における子ども達の集団衛生意識や技術の向上のみならず,子ども達が主導する地域における感染症予防啓発活動としても実施している.双方向の公衆衛生活動においては活動を支える産官学の多種多様な業種の繋がりの役割が大きい.今後の課題としては,教員のみならず児童会や生徒会を介して子どもと研究班との直接的な関係強化の必要性が挙げられる.更には,活動の持続可能性を助長する活動資金を確保し,地域における子ども主導の活動に移行していくことが必要と考えている.(著者抄録)

子ども達から市民に届ける感染症予防啓発活動コロナ禍における学校と連携した手洗い活動

大浦麻絵, 大西浩文, 助友裕子, 小山雅之, 長多好恵, 長谷川準子, 森満

札幌保健科学雑誌 ( 札幌医科大学保健医療学部 ) ( 11 ) 1 - 6 2022年03月

本稿においては,我々が地域における公衆衛生活動の一環として実施している「学童における感染症予防教育活動」を紹介する.本活動は2017年から開始され,地域における子ども達の集団衛生意識や技術の向上のみならず,子ども達が主導する地域における感染症予防啓発活動としても実施している.双方向の公衆衛生活動においては活動を支える産官学の多種多様な業種の繋がりの役割が大きい.今後の課題としては,教員のみならず児童会や生徒会を介して子どもと研究班との直接的な関係強化の必要性が挙げられる.更には,活動の持続可能性を助長する活動資金を確保し,地域における子ども主導の活動に移行していくことが必要と考えている.(著者抄録)

産・官・学が協働した学校教育における公衆衛生活動病気の予防プロジェクト&ありがとうプロジェクト

大浦麻絵, 大西浩文, 小山雅之, 長多好恵, 助友裕子, 長谷川準子, 西村剛, 岬真一郎, 戸島宏二, 川原知晃, 森満

北海道公衆衛生学雑誌 ( 北海道公衆衛生学会 ) 35 ( 2 ) 177 - 181 2022年03月

三密になりがちな教育現場での感染予防・感染拡大防止に貢献するとともに、新型コロナウイルス感染症に関する予防啓発・情報共有活動を2020年度から実施している。本稿では公衆衛生活動として実施している、社会を支えるすべての人々にありがとうの気持ちを伝える"ありがとうプロジェクト"、子ども達がエビデンス(科学的根拠)に基づく教育を受け、その学びの成果を社会へ発信する"病気の予防プロジェクト"において実施された保健所による教育講義についての実践報告を行う。(著者抄録)

新型コロナウイルス感染症(COVID-19)と健康リテラシー教育

大西浩文, 大浦麻絵, 小山雅之, 長多好恵, 長谷川準子, 助友裕子, 森満

北海道生命倫理研究 ( 北海道生命倫理研究会 ) 10 13 - 19 2022年03月

新型コロナウイルス感染症(COVID-19)は、社会に大きな不安をもたらし、その病気に対する不安が、偏見や差別という社会問題を引き起こしている。偏見・差別をなくすための取り組みの一つとして、児童生徒や保護者に対する感染症に関する教育や人権教育の重要性が考えられている。札幌医科大学医学部公衆衛生学講座では、これまで子ども達を対象として健康リテラシー向上を目指した感染症予防教育活動を実践してきており、その活動について紹介する。2017年より札幌市内の児童館において感染症予防教育を開始し、2018年には15の児童館、2つの小学校、1つの子育て支援センターでの活動に広がった。インフルエンザ予防について学び、学んだ知識をもとに予防に関する普及啓発ポスターを製作して公共スペースに展示することで情報発信を行った。2019年には小中学生を対象とした総合学習を行い、感染症についての知識や健康リテラシーを身につけ、エビデンスに基づく情報発信を考える機会となった。COVID-19の流行後は、これらの活動は中止となったものの、子ども達の感染予防活動を推進することが、学校現場を支援することにもつながると考え、モデル校を選出して泡石鹸を配布して手洗い活動を推進する「手洗い徹底活動プロジェクト」を開始した。また、感染拡大防止に役立つ情報共有を行う幼稚園・学校単位の仲間作りのプロジェクトも行い、参加施設の子ども達が作成したCOVID-19に関するクイズ動画が札幌ドームで上映されるなどの活動にもつながった。さらに、この活動は他地域へと広がり、高知県奈半利町においてもオンライン授業を行って、生徒達の手洗いの様子を写真に撮ってポスターにすることや川柳を作成して地域へ呼びかける活動にもつながった。我々の活動が、多くの施設、団体に賛同いただいてネットワークが広がっていき、子ども達が健康知識やヘルスリテラシーを身につけて、社会に情報発信を行うことで、地域での予防活動や差別・偏見をなくす活動へと発展できる可能性が示唆された。(著者抄録)

産・官・学が協働した学校教育における公衆衛生活動病気の予防プロジェクト&ありがとうプロジェクト

大浦麻絵, 大西浩文, 小山雅之, 長多好恵, 助友裕子, 長谷川準子, 西村剛, 岬真一郎, 戸島宏二, 川原知晃, 森満

北海道公衆衛生学雑誌 ( 北海道公衆衛生学会 ) 35 ( 2 ) 177 - 181 2022年03月

三密になりがちな教育現場での感染予防・感染拡大防止に貢献するとともに、新型コロナウイルス感染症に関する予防啓発・情報共有活動を2020年度から実施している。本稿では公衆衛生活動として実施している、社会を支えるすべての人々にありがとうの気持ちを伝える"ありがとうプロジェクト"、子ども達がエビデンス(科学的根拠)に基づく教育を受け、その学びの成果を社会へ発信する"病気の予防プロジェクト"において実施された保健所による教育講義についての実践報告を行う。(著者抄録)

Serum uric acid level is associated with an increase in systolic blood pressure over time in female subjects: Linear mixed-effects model analyses.

Kazuma Mori, Masato Furuhashi, Marenao Tanaka, Yukimura Higashiura, Masayuki Koyama, Nagisa Hanawa, Hirofumi Ohnishi

Hypertension research : official journal of the Japanese Society of Hypertension 45 ( 2 ) 344 - 353 2022年02月 [国際誌]

Whether hyperuricemia is a true risk factor for elevated blood pressure (BP) is controversial, and the sex-specific effects of serum uric acid (SUA) on BP during a follow-up period remain unclear. We investigated whether the association of SUA level with systolic or diastolic BP during a 10-year period differs by sex in a Japanese general population of individuals who received annual health examinations (n = 28,990). After exclusion of subjects who had no BP or SUA data at baseline, a total of 22,994 subjects (male/female: 14,603/8391, age: 47 ± 11 years) were recruited. After adjustment for age; body mass index; BP; SUA level; use of drugs for hyperuricemia and hypertension; diagnosis of diabetes mellitus, dyslipidemia, and chronic kidney disease; family history of hypertension; habits of current smoking and alcohol consumption at baseline; the duration of the observation period; and the interaction between each covariate and the duration of the observation period indicated a significant association of SUA level with change in systolic or diastolic BP over time. There was a significant interaction between sex and SUA level for the change in systolic BP (P = 0.003) but not the change in diastolic BP (P = 0.081). The SUA level at baseline (per 1 mg/dL) was significantly associated with a change in systolic BP over time in females (estimate: 0.073 mmHg/year, P = 0.003) but not in males (estimate: 0.020 mmHg/year, P = 0.160). In conclusion, a high SUA level at baseline is significantly associated with an increase in systolic BP over time in female individuals but not in male individuals.

日本人におけるFLIによるNAFLDの予測

高橋聖子, 田中希尚, 東浦幸村, 塙なぎさ, 大西浩文, 古橋眞人

日本内科学会雑誌 ( (一社)日本内科学会 ) 111 ( Suppl. ) 198 - 198 2022年02月

日本人におけるFLIによるNAFLDの予測

高橋聖子, 田中希尚, 東浦幸村, 塙なぎさ, 大西浩文, 古橋眞人

日本内科学会雑誌 ( (一社)日本内科学会 ) 111 ( Suppl. ) 198 - 198 2022年02月

血清尿酸値は女性において収縮期血圧の経時的な上昇と関連する線形混合効果モデルでの解析

森和真, 田中希尚, 東浦幸村, 小山雅之, 塙なぎさ, 大西浩文, 古橋眞人

日本痛風・尿酸核酸学会総会プログラム・抄録集 ( (一社)日本痛風・尿酸核酸学会 ) 55回 86 - 86 2022年01月

ICTを用いた新型コロナウイルス感染症宿泊療養者等の健康観察システム

小山雅之, 谷川琢海, 福田潤, 向原強, 藤本直樹, 高塚伸太朗, 中山龍一, 大西浩文

Journal of Epidemiology ( (一社)日本疫学会 ) 32 ( Suppl.1 ) 95 - 95 2022年01月

尿酸とCOVID-19の原因ウイルスSARS-CoV-2の宿主側受容体ACE2との関連についての検討

古橋眞人, 田中希尚, 東浦幸村, 森和真, 小山雅之, 大西浩文, 齋藤重幸, 島本和明

日本痛風・尿酸核酸学会総会プログラム・抄録集 ( (一社)日本痛風・尿酸核酸学会 ) 55回 80 - 80 2022年01月

ICTを用いた新型コロナウイルス感染症宿泊療養者等の健康観察システム

小山雅之, 谷川琢海, 福田潤, 向原強, 藤本直樹, 高塚伸太朗, 中山龍一, 大西浩文

Journal of Epidemiology ( (一社)日本疫学会 ) 32 ( Suppl.1 ) 95 - 95 2022年01月

血清尿酸値は女性において収縮期血圧の経時的な上昇と関連する線形混合効果モデルでの解析

森和真, 田中希尚, 東浦幸村, 小山雅之, 塙なぎさ, 大西浩文, 古橋眞人

日本痛風・尿酸核酸学会総会プログラム・抄録集 ( (一社)日本痛風・尿酸核酸学会 ) 55回 86 - 86 2022年01月

尿酸とCOVID-19の原因ウイルスSARS-CoV-2の宿主側受容体ACE2との関連についての検討

古橋眞人, 田中希尚, 東浦幸村, 森和真, 小山雅之, 大西浩文, 齋藤重幸, 島本和明

日本痛風・尿酸核酸学会総会プログラム・抄録集 ( (一社)日本痛風・尿酸核酸学会 ) 55回 80 - 80 2022年01月

Effect of comprehensive cancer genomic profiling on therapeutic strategies and clinical outcomes in patients with advanced biliary tract cancer: A prospective multicenter study.

Kohichi Takada, Tomohiro Kubo, Junko Kikuchi, Makoto Yoshida, Ayako Murota, Yohei Arihara, Hajime Nakamura, Hiroyuki Nagashima, Hiroki Tanabe, Shintaro Sugita, Yumi Tanaka, Ayana Miura, Yoshihito Ohhara, Atsushi Ishiguro, Hiroshi Yokouchi, Yasuyuki Kawamoto, Yusuke Mizukami, Hirofumi Ohnishi, Ichiro Kinoshita, Akihiro Sakurai

Frontiers in oncology 12 988527 - 988527 2022年 [国際誌]

Characterization of the genomic landscape of biliary tract cancer (BTC) may lead to applying genotype-matched therapy for patients with this disease. Evidence that comprehensive cancer genomic profiling (CGP) guides genotype-matched therapy to improve clinical outcomes is building. However, the significance of CGP in patients with BTC remains unclarified in clinical practice. Therefore, the purposes of this study were to assess the utility of CGP and identify associations between clinical outcomes and genomic alterations in patients with BTC. In this prospective analysis, detection rates for actionable genomic alterations and access rates for genotype-matched therapy were analyzed in 72 patients with advanced BTC who had undergone commercial CGP. Cox regression analyses assessed relationships between overall survival and genomic alterations detected with CGP. The most common genomic alterations detected were TP53 (41, 56.9%), followed by CDKN2A/B (24, 33.3%/20, 27.8%), and KRAS (20, 27.8%). Actionable genomic alterations were identified in 58.3% (42/72) of patients. Detection rates for FGFR2 fusions, IDH1 mutations, and BRAF V600E were low in this cohort. Eight (11.1%) patients received genotype-matched therapy. For patients with intrahepatic cholangiocarcinoma (ICC), CDKN2A/B loss was associated with shorter overall survival. These real-world data demonstrate that CGP can identify therapeutic options in patients with advanced BTC. CDKN2A/B loss was identified as a poor prognostic factor in patients with ICC. Thus, this study provides a rationale for considering CGP in planning therapeutic strategies for advanced BTC.

Prediction of Lifetime Risk of Cardiovascular Disease Deaths Stratified by Sex in the Japanese Population.

Yukiko Imai, Sachiko Mizuno Tanaka, Michihiro Satoh, Takumi Hirata, Yoshitaka Murakami, Katsuyuki Miura, Takashi Waki, Aya Hirata, Toshimi Sairenchi, Fujiko Irie, Mizuki Sata, Toshiharu Ninomiya, Takayoshi Ohkubo, Shizukiyo Ishikawa, Yoshihiro Miyamoto, Hirofumi Ohnishi, Shigeyuki Saitoh, Akiko Tamakoshi, Michiko Yamada, Masahiko Kiyama, Hiroyasu Iso, Kiyomi Sakata, Hideaki Nakagawa, Akira Okayama, Hirotsugu Ueshima, Tomonori Okamura

Journal of the American Heart Association 10 ( 23 ) e021753 2021年12月 [国際誌]

Background Lifetime risk is an informative estimate for driving lifestyle and behavioral changes especially for young adults. The impact of composite risk factors for cardiovascular disease on lifetime risk stratified by sex has not been investigated in the Japanese population, which has a much lower mortality of coronary heart disease compared with the Western population. We aimed to estimate lifetime risk of death from cardiovascular disease attributable to traditional risk factors. Methods and Results We analyzed pooled individual data from the Evidence for Cardiovascular Prevention from Observational Cohorts in a Japanese cohort study. A modified Kaplan-Meier approach was used to estimate the remaining lifetime risk of cardiovascular death. In total, 41 002 Japanese men and women with 537 126 person-years of follow-up were included. The lifetime risk at the index-age of 45 years for those with optimal risk factors (total cholesterol <4.65 mmol/L, systolic blood pressure <120 mm Hg, diastolic blood pressure <80 mm Hg, absence of diabetes, and absence of smoking habit) was lower compared with the highest risk profile of ≥2 risk factors (6.8% [95% CI, 0%-11.9%] versus 19.4% [16.7%-21.4%] for men and 6.9% [1.2%-11.5%] versus 15.4% [12.6%-18.1%] for women). Conclusions The magnitude and the number of risk factors were progressively associated with increased lifetime risk even in individuals in early adulthood who tend to have low short-term risk. The degree of established cardiovascular risk factors can be converted into lifetime risk. Our findings may be useful for risk communication in the early detection of future cardiovascular disease risk.

High level of fatty liver index predicts new onset of diabetes mellitus during a 10-year period in healthy subjects

Yukimura Higashiura, Masato Furuhashi, Marenao Tanaka, Satoko Takahashi, Masayuki Koyama, Hirofumi Ohnishi, Keita Numata, Takashi Hisasue, Nagisa Hanawa, Norihito Moniwa, Kazufumi Tsuchihashi, Tetsuji Miura

Scientific Reports ( Springer Science and Business Media LLC ) 11 ( 1 ) 12830 - 12830 2021年12月 [国際誌]

AbstractFatty liver index (FLI), a predictor of nonalcoholic fatty liver disease, has been reported to be associated with several metabolic disorders. This study aimed to evaluate the relationship between FLI and new onset of diabetes mellitus (DM). We investigated the association of FLI with new onset of DM during a 10-year period in subjects who received annual health examinations (n = 28,990). After exclusion of subjects with DM at baseline and those with missing data, a total of 12,290 subjects (male/female: 7925/4365) who received health examinations were recruited. FLI was significantly higher in males than in females. During the 10-year period, DM was developed in 533 males (6.7%) and 128 females (2.9%). Multivariable Cox proportional hazard models with a restricted cubic spline showed that the risk of new onset of DM increased with a higher FLI at baseline in both sexes after adjustment of age, fasting plasma glucose, habits of alcohol drinking and current smoking, family history of DM and diagnosis of hypertension and dyslipidemia at baseline. When the subjects were divided into subgroups according to tertiles of FLI level at baseline (T1–T3) in the absence and presence of impaired fasting glucose (IFG), hazard ratios after adjustment of the confounders gradually increased from T1 to T3 and from the absence to presence of IFG in both male and female subjects. In conclusion, a high level of FLI predicts new onset of DM in a general population of both male and female individuals.

Fatty liver index is independently associated with deterioration of renal function during a 10-year period in healthy subjects

Satoko Takahashi, Marenao Tanaka, Masato Furuhashi, Norihito Moniwa, Masayuki Koyama, Yukimura Higashiura, Arata Osanami, Yufu Gocho, Hirofumi Ohnishi, Keita Numata, Takashi Hisasue, Nagisa Hanawa, Tetsuji Miura

Scientific Reports ( Springer Science and Business Media LLC ) 11 ( 1 ) 2021年12月

AbstractA potential link between chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) has been suggested. We investigated the relationship between fatty liver index (FLI), a noninvasive and simple predictor of NAFLD, and the development of CKD defined as estimated glomerular filtration rate < 60 mL/min/1.73 m² or positive for urinary protein during a 10-year follow-up period in subjects who received annual health examinations (n = 28,890). After exclusion of CKD at baseline, a total of 14,163 subjects (male/female: 9077/5086) were recruited. During the 10-year period, 1458 males (16.1%) and 737 females (14.5%) had new onset of CKD. Multivariable Cox proportional hazard models with a restricted cubic spline showed that hazard ratios (HRs) of CKD development increased with a higher FLI at baseline in both males and females after adjustment of confounders. When divided by tertiles of FLI level at baseline (T1 ~ T3), the adjusted risk of CKD development in the T3 group (HR [95% confidence interval], male/female: 1.33 [1.16–1.54]/1.33 [1.08–1.63]) was significantly higher than that in both sexes in the T1 group as the reference. The addition of FLI into traditional risk factors significantly improved the discriminatory capability for predicting CKD. In conclusion, a high level of FLI predicts the development of CKD in both sexes in a general population.

Prognostic value of 6-min walk stress echocardiography in patients with interstitial lung disease.

Kenji Yasui, Satoshi Yuda, Kiyoshi Abe, Kouichi Asanuma, Nozomi Yanagihara, Yuta Sudo, Kimiyuki Ikeda, Atsuko Muranaka, Mitsuo Otsuka, Daigo Nagahara, Hirofumi Ohnishi, Hiroki Takahashi, Tetsuji Miura, Satoshi Takahashi

Journal of echocardiography 19 ( 4 ) 232 - 242 2021年12月 [国内誌]

BACKGROUND: The 6-min walk test (6MWT) provides prognostic information for patients with interstitial lung disease (ILD). Parameter determined by Doppler echocardiography after the 6MWT (6 MW stress echocardiography) is shown to be a predictor of future development of pulmonary hypertension in patients with connective tissue disease. However, the clinical utility of 6 MW stress echocardiography in predicting cardiopulmonary events in patients with ILD remains unknown. We examined whether parameters determined by 6 MW stress echocardiography independent predictors of adverse events in patients with ILD. METHODS: Echocardiographic examinations were performed in 68 consecutively enrolled patients with ILD (age, 65 ± 10 years, 65% men). A pressure gradient of tricuspid regurgitation (TRPG) and pulmonary vascular resistance (PVRecho) calculated using the following formula [PVRecho = (peak velocity of TR × 10/time-velocity integral of right ventricular outflow (RVOT-VTI)) + 0.16] were measured at baseline and at post 6MWT. Data for parameters of pulmonary functional tests and for 6MWT were collected. RESULTS: During a mean follow-up period of 22 ± 12 months, 22 patients experienced cardiopulmonary events. In univariate analysis, %VC, TRPG, PVRecho, TRPG post 6MWT, and PVRecho post 6MWT were significantly associated with cardiopulmonary events. Multivariate analysis using the Cox proportional hazards model indicated that %VC [hazard ratio (HR): 0.97, p = 0.009] and PVRecho post 6MWT (HR: 1.77, p = 0.004) were independent predictors of cardiopulmonary events in patients with ILD. CONCLUSIONS: In addition to parameters of pulmonary function tests, increased PVRecho post 6MWT is a significant predictor of cardiopulmonary events in patients with ILD. A 6 MW stress echocardiography is useful in assessing the risk of adverse events in patients with ILD.

学校と連携をした地域におけるソーシャルキャピタルの構築ありがとうプロジェクト先行実践校のとりくみ

大浦麻絵, 大西浩文, 小山雅之, 助友裕子, 長多好恵, 長谷川準子, 森満

北海道公衆衛生学雑誌 ( 北海道公衆衛生学会 ) 35 ( 1特別付録 ) 26 - 26 2021年11月

外国人患者の当院受療時ニーズに関する社会疫学的調査(第4報)

鈴村美和, 菅原誠, 鈴村滋生, 森満, 大西浩文

日本公衆衛生学会総会抄録集 ( 日本公衆衛生学会 ) 80回 489 - 489 2021年11月

Relationship Between Plantar Callosity and Foot Deformity in Hallux Valgus Using Weightbearing Computed Tomography

Yasutaka Murahashi, Kousuke Iba, Atsushi Teramoto, Katsunori Takahashi, Yohei Okada, Tomoaki Kamiya, Hiroyuki Takashima, Kota Watanabe, Hirofumi Ohnishi, Toshihiko Yamashita

JOURNAL OF FOOT & ANKLE SURGERY ( ELSEVIER SCIENCE INC ) 60 ( 6 ) 1207 - 1211 2021年11月

Plantar callosities under lesser metatarsals are often accompanied by the hallux valgus, and the cause of callosity is thought to be associated with the foot deformity, such as the metatarsal length discrepancy, the abnormal metatarsal head height, cavus, flat foot, and rheumatoid conditions. However, it is unclear which variable is most involved in the cause of callosity in hallux valgus deformity. To clarify the factors associated with the callosity with hallux valgus deformity, we conducted multiple image assessments based on weightbearing radiography and computed tomography. A retrospective review was performed based on the collection of clinical records from all patients with hallux valgus treated from 2010 to 2019 in our institution. We measured the hallux valgus angle, intermetatarsal angles, calcaneal pitch angles, talo-first metatarsal angles, metatarsal length, metatarsal head height, first metatarsal pronation angles, and sesamoid position with weightbearing radiography and computed tomography. We analyzed the relation between callosity formation and imaging assessments using univariate and multivariate logistic regression models. Fifty feet were retrospectively evaluated, and multiple logistic analyses by the stepwise method revealed that the first metatarsal-lateral-sesamoid distance was the only radiographical variable associated with callosity formation among all the tested variables (p < .001). As the grade of the callosity became more severe, the lateral shift of the lateral sesamoid increased. The position of the sesamoid bone appears to have a critical role in the assessment and choice of treatment protocols and further research needs to be conducted on the relationship with the position of sesamoid bone to elucidate the mechanism of callus formation. (c) 2021 by the American College of Foot and Ankle Surgeons. All rights reserved.

学校と連携をした地域におけるソーシャルキャピタルの構築ありがとうプロジェクト先行実践校のとりくみ

大浦麻絵, 大西浩文, 小山雅之, 助友裕子, 長多好恵, 長谷川準子, 森満

北海道公衆衛生学雑誌 ( 北海道公衆衛生学会 ) 35 ( 1特別付録 ) 26 - 26 2021年11月

Fatty Liver Index(FLI)は新規高血圧発症の独立した予測因子である

東浦幸村, 古橋眞人, 田中希尚, 高橋聖子, 山下智久, 小山雅之, 大西浩文, 斎藤重幸, 三浦哲嗣, 塙なぎさ

日本高血圧学会総会プログラム・抄録集 ( (NPO)日本高血圧学会 ) 43回 217 - 217 2021年10月

一般住民におけるFatty Liver Index(FLI)と高血圧発症との関連

東浦幸村, 古橋眞人, 田中希尚, 大西浩文, 三浦哲嗣

日本動脈硬化学会総会プログラム・抄録集 ( (一社)日本動脈硬化学会 ) 53回 186 - 186 2021年10月

Fatty Liver Index(FLI)は新規高血圧発症の独立した予測因子である

東浦幸村, 古橋眞人, 田中希尚, 高橋聖子, 山下智久, 小山雅之, 大西浩文, 斎藤重幸, 三浦哲嗣, 塙なぎさ

日本高血圧学会総会プログラム・抄録集 ( (NPO)日本高血圧学会 ) 43回 217 - 217 2021年10月

一般住民におけるFatty Liver Index(FLI)と高血圧発症との関連

東浦幸村, 古橋眞人, 田中希尚, 大西浩文, 三浦哲嗣

日本動脈硬化学会総会プログラム・抄録集 ( (一社)日本動脈硬化学会 ) 53回 186 - 186 2021年10月

Distinct Regulation of U-ACE2 and P-ACE2 (Urinary and Plasma Angiotensin-Converting Enzyme 2) in a Japanese General Population

Masato Furuhashi, Akiko Sakai, Marenao Tanaka, Yukimura Higashiura, Kazuma Mori, Masayuki Koyama, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto

Hypertension ( Ovid Technologies (Wolters Kluwer Health) ) 78 ( 4 ) 1138 - 1149 2021年08月 [国際誌]

Severe acute respiratory syndrome coronavirus 2 in coronavirus disease 2019 invades the host through ACE (angiotensin-converting enzyme) 2 as the host cellular receptor for a viral spike protein. ACE2 converts angiotensin II to angiotensin-(1–7) and cleaved ACE2 is detectable in urine and plasma. However, regulation of U-ACE2 (urinary ACE2) and P-ACE2 (plasma ACE2) and their alterations by renin-angiotensin-aldosterone system inhibitors remain unclear. We simultaneously investigated U-ACE2 and P-ACE2 in 605 Japanese participants (male/female: 280/325, mean age: 65±15 years) in the Tanno-Sobetsu cohort study in 2017. Males had significantly lower U-ACE2 and higher P-ACE2 than did females. There was no significant correlation between U-ACE2 and P-ACE2. P-ACE2 was significantly lower in subjects treated with renin-angiotensin-aldosterone system inhibitors than in those not treated with renin-angiotensin-aldosterone system inhibitors, but there was no significant difference in U-ACE2 between the groups. Multivariable regression analyses showed that female sex, high levels of systolic blood pressure, hemoglobin A1c, and urinary albumin-to-creatinine ratio, and low uric acid level were independent predictors of high U-ACE2 level and that high levels of γ-glutamyl transpeptidase, estimated glomerular filtration rate, and uric acid were independent predictors of high P-ACE2 level. In conclusion, U-ACE2 and P-ACE2 are distinctly regulated and the use of renin-angiotensin-aldosterone system inhibitors is not an independent predictor of their levels in a Japanese general population. U-ACE2 is associated with high blood pressure, high glucose level, and microalbuminuria, and low urate level, whereas P-ACE2 is associated with liver dysfunction, high glomerular filtration rate, and high urate level.

Reduction in GLP-1 secretory capacity may be a novel independent risk factor of coronary artery stenosis.

Chihiro Nagase, Masaya Tanno, Hidemichi Kouzu, Takayuki Miki, Junichi Nishida, Naoto Murakami, Nobuaki Kokubu, Nobutaka Nagano, Ryo Nishikawa, Nobuhiro Yoshioka, Tohru Hasegawa, Hiroyuki Kita, Akihito Tsuchida, Hirofumi Ohnishi, Tetsuji Miura

Scientific reports 11 ( 1 ) 15578 - 15578 2021年08月 [国際誌]

Multiple factors regulate glucagon-like peptide-1 (GLP-1) secretion, but a group of apparently healthy subjects showed blunted responses of GLP-1 secretion in our previous study. In this study, we examined whether the reduction in GLP-1 secretory capacity is associated with increased extent of coronary artery stenosis in non-diabetic patients. Non-diabetic patients who were admitted for coronary angiography without a history of coronary interventions were enrolled. Coronary artery stenosis was quantified by Gensini score (GS), and GS ≥ 10 was used as an outcome variable based on its predictive value for cardiovascular events. The patients (mean age, 66.5 ± 8.8 years; 71% males, n = 173) underwent oral 75 g-glucose tolerant tests for determination of glucose, insulin and active GLP-1 levels. The area under the curve of plasma active GLP-1 (AUC-GLP-1) was determined as an index of GLP-1 secretory capacity. AUC-GLP-1 was not correlated with fasting glucose, AUC-glucose, serum lipids or indices of insulin sensitivity. In multivariate logistic regression analysis for GS ≥ 10, AUC-GLP-1 < median, age and hypertension were selected as explanatory variables, though fasting GLP-1 level was not selected. The findings suggest that reduction in GLP-1 secretory capacity is a novel independent risk factor of coronary stenosis.

Independent Association of Fatty Liver Index With Left Ventricular Diastolic Dysfunction in Subjects Without Medication

Masato Furuhashi, Atsuko Muranaka, Satoshi Yuda, Marenao Tanaka, Masayuki Koyama, Mina Kawamukai-Nishida, Satoko Takahashi, Yukimura Higashiura, Daisuke Miyamori, Ryo Nishikawa, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

The American Journal of Cardiology ( Elsevier BV ) 158 139 - 146 2021年08月 [国際誌]

Nonalcoholic fatty liver disease has been reported to be potentially linked to cardiovascular disease. Fatty liver index (FLI) is a noninvasive and simple predictor of nonalcoholic fatty liver disease. However, little is known about the relationship between FLI and cardiac function, especially in a general population. We investigated the relationships of FLI with echocardiographic parameters in 185 subjects (men/women: 79/106) of the Tanno-Sobetsu Study, a population-based cohort, who were not being treated with any medication and who underwent echocardiography. FLI was negatively correlated with high-density lipoprotein cholesterol and peak myocardial velocity during early diastole (e'; r = -0.342, p <0.001), an index of left ventricular (LV) diastolic function, and ratio of peak mitral velocities during early and late diastole (E/A) and was positively correlated with age, systolic and diastolic blood pressures, creatinine, uric acid, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein, ratio of mitral to myocardial early diastolic peak velocity (E/e'), left atrial volume index and LV mass index. No significant correlation was found between FLI and LV ejection fraction. Stepwise multivariable regression analysis showed that FLI was independently and negatively associated with e' after adjustment of age, gender, high-density lipoprotein cholesterol, homeostasis model assessment of insulin resistance, and high-sensitivity C-reactive protein. Conversely, e' was independently and negatively associated with FLI after adjustment of age, gender, systolic blood pressure, and LV ejection fraction. In conclusion, elevated FLI is independently associated with LV diastolic dysfunction in a general population without medication. FLI would be a novel marker of LV diastolic dysfunction as an early sign of myocardial injury.

Elevated Fatty Liver Index Is Independently Associated With New Onset of Hypertension During a 10‐Year Period in Both Male and Female Subjects

Yukimura Higashiura, Masato Furuhashi, Marenao Tanaka, Satoko Takahashi, Kazuma Mori, Daisuke Miyamori, Masayuki Koyama, Hirofumi Ohnishi, Norihito Moniwa, Keita Numata, Takashi Hisasue, Nagisa Hanawa, Tetsuji Miura

Journal of the American Heart Association ( Ovid Technologies (Wolters Kluwer Health) ) 10 ( 14 ) e021430 2021年07月 [国際誌]

Background

Fatty liver index (FLI), a predictor of nonalcoholic fatty liver disease, has been reported to be associated with several metabolic disorders. Because of a sex difference in FLI level, we hypothesized that FLI is associated with development of hypertension to a greater extent in men or women. Methods and Results

We investigated the relationship between FLI and development of hypertension during a 10‐year period in a general population of subjects who received annual health examinations (n=28 990). After exclusion (44.9%) of subjects with missing data and those with hypertension at baseline, a total of 15 965 subjects (men/women: 9466/6499) were included. FLI level was significantly higher in men than in women. During the 10‐year period, 2304 men (24.3%) and 745 women (11.5%) had new onset of hypertension. Multivariable Cox proportional hazard models with a restricted cubic spline showed that the hazard ratios (HRs) for development of hypertension after adjustment of age, systolic blood pressure, estimated glomerular filtration rate, habits of smoking and alcohol drinking, family history of hypertension, and diagnosis of diabetes mellitus and dyslipidemia increased gradually with increase in FLI in men and increased rapidly and then slowly with increase in FLI in women. There was a significant interaction between FLI and sex for the risk of hypertension in all of the subjects ( P =0.049). The addition of FLI to traditional risk factors significantly improved the discriminatory capability. Conclusions

A high level of FLI predicts the development of hypertension in both men and women, although distribution patterns of HRs were different between sexes.

Seasonal variation of serum 25-hydroxyvitamin D level in hemodialysis patients in the northernmost island of Japan

Yufu Gocho, Marenao Tanaka, Hirohito Sugawara, Masato Furuhashi, Norihito Moniwa, Tomohisa Yamashita, Hideki Takizawa, Hiroya Mukai, Kouhei Ohno, Takuto Maeda, Arata Osanami, Hirofumi Ohnishi, Hiroaki Komatsu, Kazuma Mori, Tetsuji Miura

Clinical and Experimental Nephrology ( Springer Science and Business Media LLC ) 25 ( 12 ) 1360 - 1366 2021年07月 [国内誌]

BACKGROUND: Serum vitamin D level shows a seasonal variation, being lower in winter than in summer in healthy subjects. The aim of this study was to determine whether there is presence of such a seasonal variation in hemodialysis patients. METHODS: A total of 102 patients on hemodialysis were enrolled in February 2017 (winter) for analyses of serum levels of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and treatments for chronic kidney disease-mineral and bone disorder (CKD-MBD). The examinations were repeated in August 2017 (summer). After exclusion of patients with malignancy, loss of follow-up and missing data, 78 patients contributed to the analyses. RESULTS: Serum level of 25(OH)D, but not that of 1,25(OH)2D, was significantly lower in winter (14.0 ng/mL) than in summer (15.5 ng/mL), though there was no significant difference in regimen for CKD-MBD treatment including vitamin D receptor activators (VDRAs) between the two seasons. Serum intact parathyroid hormone level tended to be higher and alkaline phosphatase was significantly higher in winter than in summer. Linear mixed-effects model analysis showed that level of 25(OH)D, but not that of 1,25(OH)2D, was significantly associated with season (winter and summer) after adjustment of age, sex, dialysis vintage, albumin level and use of drugs for CKD-MBD. CONCLUSION: Serum 25(OH)D has a seasonal variation, being lower in winter than in summer, independent of CKD-MBD treatment including treatment with VDRAs in Japanese hemodialysis patients. The impact of the seasonal variation on risk of vitamin D deficiency and its effect on prognosis remain to be investigated.

Independent association of plasma xanthine oxidoreductase activity with hypertension in nondiabetic subjects not using medication.

Masato Furuhashi, Yukimura Higashiura, Masayuki Koyama, Marenao Tanaka, Takayo Murase, Takashi Nakamura, Seigo Akari, Akiko Sakai, Kazuma Mori, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

Hypertension research : official journal of the Japanese Society of Hypertension 44 ( 9 ) 1213 - 1220 2021年06月 [国際誌]

Xanthine oxidoreductase (XOR), a rate-limiting and catalyzing enzyme of uric acid formation in purine metabolism, is involved in reactive oxygen species generation. Plasma XOR activity has been shown to be a novel metabolic biomarker related to obesity, liver dysfunction, hyperuricemia, dyslipidemia, and insulin resistance. However, the association between plasma XOR activity and hypertension has not been fully elucidated. We investigated the association of hypertension with plasma XOR activity in 271 nondiabetic subjects (male/female: 119/152) who had not taken any medications in the Tanno-Sobetsu Study, a population-based cohort. Males had higher plasma XOR activity than females. Plasma XOR activity was positively correlated with mean arterial pressure (r = 0.128, P = 0.036). When the subjects were divided by the presence and absence of hypertension into an HT group (male/female: 34/40) and a non-HT group (male/female: 85/112), plasma XOR activity in the HT group was significantly higher than that in the non-HT group (median: 39 vs. 28 pmol/h/mL, P = 0.028). There was no significant difference in uric acid levels between the two groups. Multivariable logistic regression analysis showed that plasma XOR activity (odds ratio: 1.091 [95% confidence interval: 1.023-1.177] per 10 pmol/h/mL, P = 0.007) was an independent determinant of the risk for hypertension after adjustment for age, sex, current smoking and alcohol consumption, estimated glomerular filtration rate, brain natriuretic peptide, and insulin resistance index. The interaction of sex with plasma XOR activity was not significant for the risk of hypertension. In conclusion, plasma XOR activity is independently associated with hypertension in nondiabetic individuals who are not taking any medications.

CKD発症予測におけるfatty liver indexの意義

高橋聖子, 田中希尚, 古橋眞人, 長南新太, 宮森大輔, 後町結, 塙なぎさ, 茂庭仁人, 大西浩文, 三浦哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 ) 63 ( 4 ) 453 - 453 2021年06月

CKD発症予測におけるfatty liver indexの意義

高橋聖子, 田中希尚, 古橋眞人, 長南新太, 宮森大輔, 後町結, 塙なぎさ, 茂庭仁人, 大西浩文, 三浦哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 ) 63 ( 4 ) 453 - 453 2021年06月

Does renin‐angiotensin system inhibition have impacts on muscle mass and bone mineral density in heart failure patients?

Satoshi Katano, Toshiyuki Yano, Masaki Shimizu, Katsuhiko Ohori, Hidemichi Kouzu, Masayuki Koyama, Ryohei Nagaoka, Takuya Inoue, Yuhei Takamura, Tomoyuki Ishigo, Hiroyuki Takashima, Masaki Katayose, Hirofumi Ohnishi, Tetsuji Miura

ESC Heart Failure ( Wiley ) 2021年05月

【健康教育・ヘルスプロモーションとCOVID-19】小学生における感染症予防に関する情報発信活動小学校教科「総合的な学習の時間」を活用した取り組み

大浦麻絵, 大西浩文, 小山雅之, 長多好恵, 長谷川準子, 助友裕子, 森満

日本健康教育学会誌 ( (一社)日本健康教育学会 ) 29 ( 2 ) 215 - 222 2021年05月

北海道のST上昇型急性心筋梗塞における総虚血時間と再灌流療法選択の実態

親谷佳佑, 小山雅之, 大西浩文, 三浦哲嗣

日本循環器病予防学会誌 ( (一社)日本循環器病予防学会 ) 56 ( 2 ) 173 - 173 2021年05月

【健康教育・ヘルスプロモーションとCOVID-19】小学生における感染症予防に関する情報発信活動小学校教科「総合的な学習の時間」を活用した取り組み

大浦麻絵, 大西浩文, 小山雅之, 長多好恵, 長谷川準子, 助友裕子, 森満

日本健康教育学会誌 ( (一社)日本健康教育学会 ) 29 ( 2 ) 215 - 222 2021年05月

目的:「病気の予防プロジェクト」は児童が感染症予防について主体的に学び,全校や市民に向けて情報発信することを目的として行われた.活動内容:小学校と医学系研究者とが協働をした20時間を超える学習プログラム「病気の予防プロジェクト」を2019年から小学校教育の中で始動した.2019年度はインフルエンザ感染症予防,2020年度は新型コロナウイルス感染症予防について学習し,予防についての情報発信を行った.札幌市立N小学校6年生の総合的な学習の時間の中で実施され,2019年度は75人,2020年度は82人の全児童が受講した.活動評価・今後の課題:児童が主体性や活動範囲をより伸ばすことができたことが評価される.児童においては取り組みの温度差が課題として挙げられる.また,科学的検証視点を入れていくことや,児童からの健康情報の伝達の他に,保護者側からのアドバイスなど家庭で取り組む学びの支援などを構築していくことも課題となる.(著者抄録)

北海道のST上昇型急性心筋梗塞における総虚血時間と再灌流療法選択の実態

親谷佳佑, 小山雅之, 大西浩文, 三浦哲嗣

日本循環器病予防学会誌 ( (一社)日本循環器病予防学会 ) 56 ( 2 ) 173 - 173 2021年05月

「地域で子ども達を守ろう!新型コロナウイルス撃退大作戦」始動までの道のり

大浦麻絵, 大西浩文, 小山雅之, 長多好恵, 長谷川準子, 助友裕子, 森満

北海道の公衆衛生 ( 北海道公衆衛生協会 ) ( 47 ) 65 - 66 2021年03月

Possible clinical outcomes using early enteral nutrition in individuals with allogeneic hematopoietic stem cell transplantation: A single-center retrospective study

Satoshi Iyama, Hiroomi Tatsumi, Tsukasa Shiraishi, Masahiro Yoshida, Ayumi Tatekoshi, Akihito Endo, Taichiro Ishige, Yuh Shiwa, Soushi Ibata, Akari Goto, Kana Nagashima, Hiroto Horiguchi, Chisa Fujita, Hiroshi Ikeda, Kohichi Takada, Takayuki Nobuoka, Yusuke Kamihara, Shohei Kikuchi, Tsutomu Sato, Hirofumi Ohnishi, Shin-ichi Yokota, Masayoshi Kobune

Nutrition ( Elsevier BV ) 83 111093 - 111093 2021年03月

冠動脈狭窄症における危険因子の管理と病変分布との関連 BOREAS-CAGレジストリデータのクロスセクション分析(Relationship between Risk Factor Management and Lesion Distribution in Coronary Artery Stenosis: A Cross-sectional Analysis of BOREAS-CAG Registry Data)

高橋遼, 國分宣明, 小山雅之, 岸上直広, 中田潤, 西川諒, 村上直人, 永野伸卓, 丹野雅也, 大西浩文, 橋本暁佳, 土橋和文, 三浦哲嗣

日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 ) 85回 OJ06 - 3 2021年03月

冠動脈狭窄症における危険因子管理と病変分布との関連:BOREAS-CAGレジストリデータの横断的分析

高橋遼, 國分宣明, 小山雅之, 岸上直広, 中田潤, 西川諒, 村上直人, 永野伸卓, 丹野雅也, 大西浩文, 橋本暁佳, 土橋和文, 三浦哲嗣

日本循環器学会学術集会(Web) ( (一社)日本循環器学会 ) 85回 OJ06 - 3 2021年03月

COVID-19感染拡大期における学校教育・保育活動を支える公衆衛生活動活動と拡がり

大浦麻絵, 大西浩文, 小山雅之, 長多好恵, 長谷川準子, 助友裕子, 森満

北海道公衆衛生学雑誌 ( 北海道公衆衛生学会 ) 34 ( 2 ) 159 - 163 2021年03月

2020年、新型コロナウイルス感染症が世界的に流行した。集団生活を営む学校現場の感染症予防の一つとして、子どもたち一人ひとりが意識し徹底して行う手洗い活動は大きな予防策となりうると考えられる。我々は手洗い指導・活動を徹底的に実践するためのモデル校を選出し、一年間徹底的活動を行うために必要な泡石鹸を配給する公衆衛生活動を実施している。そして、子ども達が予防啓発ポスターや川柳制作など自分にできることを行い、社会に情報発信するシステム構築を目指し取り組んでいる。本稿は2020年7月から実施している公衆衛生活動の内容とその拡がりについての報告である。(著者抄録)

循環FABP4濃度の上昇は,一般集団の心血管死を予測する:12年間の前向き研究

齋藤礼衣, 古橋眞人, 小山雅之, 東浦幸村, 赤坂憲, 田中希尚, 茂庭仁人, 大西浩文, 齋藤重幸, 浦信行, 島本和明, 三浦哲嗣

日本循環器学会学術集会(Web) 11 ( 1 ) 4008 - 4008 2021年02月 [国際誌]

Fatty acid-binding protein 4 (FABP4) is secreted from adipose tissue and acts as an adipokine, and an elevated circulating FABP4 level is associated with metabolic disorders and atherosclerosis. However, little is known about the causal link between circulating FABP4 level and mortality in a general population. We investigated the relationship between FABP4 concentration and mortality including cardiovascular death during a 12-year period in subjects of the Tanno-Sobetsu Study, a population-based cohort (n = 721, male/female: 302/419). FABP4 concentration at baseline was significantly higher in female subjects than in male subjects. All-cause death occurred in 123 (male/female: 74/49) subjects, and 34 (male/female: 20/14) and 42 (male/female: 26/16) subjects died of cardiovascular events and cancer, respectively. When divided into 3 groups according to tertiles of FABP4 level at baseline by sex (T1-T3), Kaplan-Meier survival curves showed that there were significant differences in rates of all-cause death and cardiovascular death, but not cancer death, among the groups. Multivariable Cox proportional hazard model analysis with a restricted cubic spline showed that hazard ratio (HR) for cardiovascular death, but not that for all-cause death, significantly increased with a higher FABP4 level at baseline after adjustment of age and sex. The risk of cardiovascular death after adjustment of age, sex, body mass index and levels of brain natriuretic peptide and high-sensitivity C-reactive protein in the 3rd tertile (T3) group (HR: 4.96, 95% confidence interval: 1.20-22.3) was significantly higher than that in the 1st tertile (T1) group as the reference. In conclusion, elevated circulating FABP4 concentration predicts cardiovascular death in a general population.

DOI PubMed J-GLOBAL

介護福祉施設の入居者における内服薬と口腔の状態と機能の関連

藤井瑞恵, 山口摂崇, 大渕一博, 三谷篤史, 村松宰, 越智守生, 大西浩文, 村松真澄

Journal of Epidemiology ( (一社)日本疫学会 ) 31 ( Suppl. ) 141 - 141 2021年01月

Dilemma of physician-mothers faced with an increased home burden and clinical duties in the hospital during the COVID-19 pandemic.

Sachiyo Nishida, Kanna Nagaishi, Masayo Motoya, Ayako Kumagai, Noriko Terada, Ai Kasuga, Narumi Kubota, Kotoe Iesato, Motonobu Kimizuka, Satsuki Miyajima, Masayuki Koyama, Hirofumi Ohnishi, Eichi Narimatsu, Naoya Masumori, Kazufumi Tsuchihashi, Taiji Tsukamoto, Yoshihisa Tsuji

PloS one 16 ( 6 ) e0253646 2021年 [国際誌]

PURPOSE: Since December 2019, coronavirus disease 2019 (COVID-19) has spread rapidly across the world. During the pandemic, physicians in our hospital have had to respond both to the issue of treating the patients and the increasing domestic burden associated with social disruption. The purpose of this study was to assess how much the burden on our doctors, especially female doctors, was increasing. MATERIAL AND METHODS: The Physicians' Career Support Committee in Sapporo Medical University conducted a questionnaire survey. The questionnaire inquired about a wide range of subjects with regard to working style and family life during the first and second waves of the COVID-19 pandemic, and was sent to all medical/dental physicians working in Sapporo Medical University. RESULTS: A total of 266 (42.7%) physicians in our hospital responded to our questionnaire and the data for 264 data were analyzed. The total numbers of males, females, and others, including those who did not want to specify, were 178 (67.4%), 82 (31.0%), and 4 (1.5%), respectively. Among them, 62 (23.5%) and 23 (8.7%) answered that their domestic burden was slightly or markedly increased. The increase in the domestic burden showed a significant difference between genders (p = 0.04). Even after correction for background differences using multivariate analysis, being female (p<0.001), having child dependents (p<0.001), and treating COVID-19 patients (p = 0.03) were significantly related to an increased domestic burden. Regarding family style, 58.1% of the physician-fathers were from two-income families (i.e., families with both parents in employment), and they answered that their partner mainly cared for the children. In contrast, 97.3% of physician-mothers were from two-income families, and 94.6% of the physician-mothers had to take care of children by themselves. CONCLUSION: Physician-mothers are caught in a dilemma between an increased home burden and clinical duties in the hospital, with a significantly higher ratio than physician-fathers during the pandemic. As we showed, female doctors could have not continued their careers and take responsible positions in the same way as male doctors. This is a social risk in the timing of a crisis, such as a pandemic.

Circulating PCSK7 Level is Independently Associated with Obesity, Triglycerides Level and Fatty Liver Index in a General Population without Medication

Masato Furuhashi, Yu Kataoka, Ryo Nishikawa, Masayuki Koyama, Akiko Sakai, Yukimura Higashiura, Marenao Tanaka, Shigeyuki Saitoh, Kazuaki Shimamoto, Hirofumi Ohnishi

Journal of Atherosclerosis and Thrombosis ( Japan Atherosclerosis Society ) 2021年 [国内誌]

AIM: Dyslipidemia and altered iron metabolism are typical features of non-alcoholic fatty liver disease (NAFLD). Proprotein convertase subtilisin/kexin type 7 (PCSK7), a transmembrane-anchored endonuclease, is associated with triglycerides level and processing of transferrin receptor 1. However, the significance of circulating PCSK7 has not been fully addressed, though prosegment PCSK7 is secreted from cells. We investigated the associations of plasma PCSK7 level with several parameters. METHODS: Plasma PCSK7 concentration was measured in 282 subjects (male/female: 126/156) without medication of the Tanno-Sobetsu Study, a population-based cohort study. RESULTS: There was no significant sex difference in PCSK7 level. Current smoking habit, but not alcohol drinking habit, was associated with increased PCSK7 level. PCSK7 concentration was negatively correlated with age and blood urea nitrogen and was positively correlated with body mass index (BMI) and levels of γ-glutamyl transpeptidase (γGTP), triglycerides and fatty liver index (FLI), which is calculated by BMI, waist circumference and levels of γGTP and triglycerides, as a noninvasive and simple predictor of NAFLD. There were no significant correlations of PCSK7 level with levels of iron and plasma PCSK9, a secreted PCSK family member and a regulator of low-density lipoprotein cholesterol level. Multivariable regression analyses after adjustment of age, sex and current smoking habit showed that PCSK7 concentration was independently associated with BMI (β=0.130, P=0.035), triglycerides (β=0.141, P=0.027) or FLI (β=0.139, P=0.030). CONCLUSIONS: Plasma PCSK7 concentration is independently associated with chronic liver disease including obesity and elevated triglycerides level in a general population of individuals who had not regularly taken any medications.

Prediction of new onset of diabetes mellitus during a 10-year period by using a combination of levels of alanine aminotransferase and γ-glutamyl transferase

Daisuke Miyamori, Marenao Tanaka, Masato Furuhashi, Hirofumi Ohnishi, Masayuki Koyama, Arata Osanami, Yukimura Higashiura, Keita Numata, Takashi Hisasue, Nagisa Hanawa, Norihito Moniwa, Tetsuji Miura

Endocrine Journal ( Japan Endocrine Society ) 68 ( 12 ) 1391 - 1402 2021年 [国内誌]

Levels of alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) have been reported to be associated with increased risk of diabetes mellitus (DM). However, whether a combination of levels of ALT and GGT predicts new onset of DM better than does ALT or GGT alone in both males and females has not fully been addressed. We investigated the relationship between the combination of ALT and GGT and DM development during a 10-year follow-up period in 13,919 subjects (male/female: 8,983/4,936; age 48 ± 10 years) who received health examinations. During the 10-year period, 617 males (6.9%) and 153 females (3.1%) had new onset of DM. Multivariable Cox proportional hazard models with a restricted cubic spline showed that hazard ratios (HRs) of DM development increased with higher levels of ALT and GGT at baseline in both sexes after adjustment of confounding factors. When divided into 4 subgroups of high (H-) and low (L-) levels of ALT (male/female: 27/21 U/L) and GGT (male/female: 43/23 U/L) using cutoff values shown by receiver operating characteristic curve analyses, the adjusted HR in the H-ALT/H-GGT group was significantly higher than HR in the L-ALT/L-GGT group as the reference in males (HR [95% confidence interval]: 1.73[1.36-2.20], p < 0.001) but was not significantly higher in females (1.50 [0.97-2.33], p = 0.065). The addition of the combination of H-ALT/H-GGT to traditional risk factors with and without H-ALT or H-GGT alone significantly improved the discriminatory capability for predicting development of DM. In conclusion, the combination of H-ALT/H-GGT efficiently predicts development of DM in male individuals but not significantly in female individuals.

Relationship Between Plantar Callosity and Foot Deformity in Hallux Valgus Using Weightbearing Computed Tomography.

Yasutaka Murahashi, Kousuke Iba, Atsushi Teramoto, Katsunori Takahashi, Yohei Okada, Tomoaki Kamiya, Hiroyuki Takashima, Kota Watanabe, Hirofumi Ohnishi, Toshihiko Yamashita

The Journal of foot and ankle surgery : official publication of the American College of Foot and Ankle Surgeons 60 ( 6 ) 1207 - 1211 2021年 [国際誌]

Plantar callosities under lesser metatarsals are often accompanied by the hallux valgus, and the cause of callosity is thought to be associated with the foot deformity, such as the metatarsal length discrepancy, the abnormal metatarsal head height, cavus, flat foot, and rheumatoid conditions. However, it is unclear which variable is most involved in the cause of callosity in hallux valgus deformity. To clarify the factors associated with the callosity with hallux valgus deformity, we conducted multiple image assessments based on weightbearing radiography and computed tomography. A retrospective review was performed based on the collection of clinical records from all patients with hallux valgus treated from 2010 to 2019 in our institution. We measured the hallux valgus angle, intermetatarsal angles, calcaneal pitch angles, talo-first metatarsal angles, metatarsal length, metatarsal head height, first metatarsal pronation angles, and sesamoid position with weightbearing radiography and computed tomography. We analyzed the relation between callosity formation and imaging assessments using univariate and multivariate logistic regression models. Fifty feet were retrospectively evaluated, and multiple logistic analyses by the stepwise method revealed that the first metatarsal-lateral-sesamoid distance was the only radiographical variable associated with callosity formation among all the tested variables (p < .001). As the grade of the callosity became more severe, the lateral shift of the lateral sesamoid increased. The position of the sesamoid bone appears to have a critical role in the assessment and choice of treatment protocols and further research needs to be conducted on the relationship with the position of sesamoid bone to elucidate the mechanism of callus formation.

Impact of atrial fibrillation on the risk of ischemic stroke in patients on hemodialysis: BOREAS-HD3 Study

Ayumu Kimura, Marenao Tanaka, Norihito Moniwa, Arata Osanami, Koki Abe, Daisuke Miyamori, Yufu Gocho, Satoru Shibata, Makoto Terasawa, Yusuke Okazaki, Tomohisa Yamashita, Masayuki Koyama, Masato Furuhashi, Hirofumi Ohnishi, Tetsuji Miura

Clinical and Experimental Nephrology ( Springer Science and Business Media LLC ) 2020年11月

ICTを用いた新型コロナウイルス感染症宿泊療養者の健康観察システム

小山雅之, 谷川琢海, 福田潤, 氷見山清子, 水野浩利, 上村修二, 石井安彦, 大西浩文

医療情報学連合大会論文集 ( (一社)日本医療情報学会 ) 40回 453 - 454 2020年11月

地域在住高齢者の身体的フレイルと骨格筋量及び筋力との関連端野・壮瞥町研究

世古俊明, 赤坂憲, 樋室伸顕, 小山雅之, 齋藤重幸, 三浦哲嗣, 大西浩文

日本老年医学会雑誌 ( (一社)日本老年医学会 ) 57 ( 4 ) 496 - 497 2020年10月

外国人患者の当院受療時ニーズに関する社会疫学的調査(第3報)

鈴村美和, 菅原誠, 鈴村滋生, 森満, 大西浩文

日本公衆衛生学会総会抄録集 ( 日本公衆衛生学会 ) 79回 485 - 485 2020年10月

【糖尿病患者の血圧管理】糖尿病合併高血圧患者の薬剤選択 JSH2019改訂における重要ポイント

国村彩子, 樋室伸顕, 藤吉朗, 瀬川裕佳, 大西浩文, 斎藤重幸

月刊糖尿病 ( (株)医学出版 ) 12 ( 5 ) 24 - 28 2020年09月

U-shaped relationship between serum uric acid level and decline in renal function during a 10-year period in female subjects: BOREAS-CKD2.

Kazuma Mori, Masato Furuhashi, Marenao Tanaka, Keita Numata, Takashi Hisasue, Nagisa Hanawa, Masayuki Koyama, Arata Osanami, Yukimura Higashiura, Masafumi Inyaku, Megumi Matsumoto, Norihito Moniwa, Hirofumi Ohnishi, Tetsuji Miura

Hypertension research : official journal of the Japanese Society of Hypertension 44 ( 1 ) 107 - 116 2020年08月 [査読有り] [国際誌]

While hyperuricemia is recognized as a risk factor for chronic kidney disease (CKD), the risk of CKD in subjects with a low level of serum uric acid (UA) remains controversial. Here, we examined whether the association of CKD risk with serum UA level differs depending on the sex and age of subjects in a general population. Of subjects who received annual health checkups, we enrolled 6,779 subjects (male/female: 4,454/2,325; age: 45 ± 9 years) with data from a 10-year follow-up after excluding subjects taking anti-hyperuricemic drugs and those with CKD at baseline. During the follow-up period, 11.4% of the males and 11.7% of the females developed CKD. A significant interaction of sex, but not age, with the effect of baseline UA level on CKD risk was found. A restricted cubic spline analysis showed a U-shaped association of the baseline UA level with the risk of CKD in females. Multivariable Cox proportional hazard analyses for females showed that baseline UA levels in the 5th quintile (Q5, ≥5 mg/dL; HR: 1.68) and the 1st quintile (Q1, ≤3.5 mg/dL; HR: 1.73) were independent risk factors for CKD when compared with UA levels in the 4th quintile (Q4, 4.5-4.9 mg/dL). In males, restricted cubic spline analysis indicated increased CKD risk in subjects with a higher baseline UA level but not in those with a low UA level. In conclusion, a low UA level is a significant risk factor for CKD in females, while an elevated UA level increases the risk of CKD in both sexes.

Impact of hypertension stratified by diabetes on the lifetime risk of cardiovascular disease mortality in Japan: a pooled analysis of data from the Evidence for Cardiovascular Prevention from Observational Cohorts in Japan study.

Yukiko Imai, Takumi Hirata, Shigeyuki Saitoh, Toshiharu Ninomiya, Yoshihiro Miyamoto, Hirofumi Ohnishi, Yoshitaka Murakami, Hiroyasu Iso, Sachiko Tanaka, Katsuyuki Miura, Akiko Tamakoshi, Michiko Yamada, Masahiko Kiyama, Hirotsugu Ueshima, Shizukiyo Ishikawa, Tomonori Okamura

Hypertension research : official journal of the Japanese Society of Hypertension 43 ( 12 ) 1437 - 1444 2020年07月 [査読有り] [国際誌]

Lifetime risk is an informative estimate to motivate people to change lifestyle behaviors, especially from a younger age, in public health education. The impact of the combination of hypertension and diabetes on the lifetime risk of cardiovascular mortality has not been investigated in Asian populations. A pooled analysis of individual data from nine cohorts was performed. A total of 57,339 Japanese men and women were eligible for the analysis. We used the modified Kaplan-Meier approach and estimated the remaining lifetime risk of cardiovascular mortality starting from the index age of 35 years. Participants were classified into four categories defined by hypertension and diabetes. The lifetime risk was increased in the order of those without either risk, those without hypertension but with diabetes, those with hypertension but without diabetes, and those with both risks. The lifetime risk of cardiovascular mortality at the 35-year index age was as follows: 7.8% in men and 6.2% in women for those without either hypertension or diabetes, 13.2% in men and 9.5% in women for those without hypertension but with diabetes, 17.2% in men and 11.7% in women for those with hypertension but without diabetes, and 19.4% in men and 15% in women for those with both risks. These findings reinforce the need for a life-course perspective in the management of hypertension and diabetes from a younger age.

Fatty liver indexはCKD発症と関連する

高橋聖子, 田中希尚, 古橋眞人, 長南新太, 小山雅之, 後町結, 塙なぎさ, 茂庭仁人, 大西浩文, 三浦哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 ) 62 ( 4 ) 304 - 304 2020年07月

【高血圧学下-高血圧制圧の現状と展望-】合併症を伴った高血圧糖尿病/肥満/メタボリックシンドロームを合併した高血圧治療薬剤選択はどこまで重要か

齋藤重幸, 小山雅之, 大西浩文

日本臨床 ( (株)日本臨床社 ) 78 ( 増刊2 高血圧学(下) ) 213 - 219 2020年07月

一般住民においてヒポキサンチンとキサンチンの血中濃度は肥満によって異なった制御を受ける

古橋眞人, 東浦幸村, 小山雅之, 村瀬貴代, 中村敬志, 酒井晶子, 田中希尚, 茂庭仁人, 大西浩文, 斎藤重幸, 三浦哲嗣

痛風と尿酸・核酸 ( (一社)日本痛風・尿酸核酸学会 ) 44 ( 1 ) 94 - 94 2020年07月

【高血圧学上-高血圧制圧の現状と展望-】日本における高血圧の疫学と観察研究の最新知見日本における観察研究と高血圧の疫学端野・壮瞥町研究

齋藤重幸, 小木曽寛樹, 小山雅之, 大西浩文

日本臨床 ( (株)日本臨床社 ) 78 ( 増刊1 高血圧学(上) ) 493 - 498 2020年06月

【高血圧学上-高血圧制圧の現状と展望-】日本における高血圧の疫学と観察研究の最新知見日本における観察研究と高血圧の疫学端野・壮瞥町研究

齋藤重幸, 小木曽寛樹, 小山雅之, 大西浩文

日本臨床 ( (株)日本臨床社 ) 78 ( 増刊1 高血圧学(上) ) 493 - 498 2020年06月

Low urine pH predicts new onset of diabetes mellitus during a 10-year period in men: BOREAS-DM1 study.

Yukimura Higashiura, Marenao Tanaka, Masato Furuhashi, Masayuki Koyama, Hirofumi Ohnishi, Keita Numata, Takashi Hisasue, Nagisa Hanawa, Norihito Moniwa, Tetsuji Miura

Journal of diabetes investigation 11 ( 6 ) 1490 - 1497 2020年04月 [査読有り] [国内誌]

AIMS/INTRODUCTION: A low level of urine pH (U-pH) has been reported to be associated with metabolic disorders. However, the relationship between the incidence of diabetes mellitus and U-pH has not yet been fully addressed. MATERIALS AND METHODS: We investigated the relationship between U-pH and the development of diabetes mellitus during a 10-year period in a general population of individuals who received annual health examinations in 2006 (n = 28,990). After exclusion of individuals with missing data, and those with diabetes mellitus and/or chronic kidney disease at baseline, a total of 12,476 individuals (men/women: 8,027/4,449) who received health examinations at least once during the period from 2007 to 2016 were recruited. The recruited individuals were divided into four groups according to their U-pH levels: groups of U-pH ≤5.0, 5.5, 6.0 and ≥6.5. RESULTS: During a 10-year period, 521 men (6.5%) and 132 women (3.0%) had new onset of diabetes mellitus. The cumulative incidence of diabetes mellitus was 7.5% (men/women: 9.3%/4.4%) per 100 person-years. The hazard ratios (HRs) in the U-pH ≤5.0 (HR 1.93) and U-pH 5.5 groups (HR 1.46) were significantly higher than that in the U-pH ≥6.5 group as a reference for men, but not for women. After adjustment of age, obesity, fasting glucose, smoking and alcohol drinking habits, family history of diabetes mellitus, and use of drugs for hypertension and dyslipidemia, HR in the U-pH ≤5.0 group (HR 1.39) was significantly higher than that in the U-pH ≥6.5 group for men, but not for women. CONCLUSIONS: Low U-pH predicts new onset of diabetes mellitus in a general population of men.

ALT、γGTPの組み合わせによる糖尿病発症リスク評価の向上

宮森大輔, 田中希尚, 古橋眞人, 茂庭仁人, 三浦哲嗣, 小山雅之, 大西浩文, 沼田啓太, 久末章史, 塙なぎさ

日本内科学会雑誌 ( (一社)日本内科学会 ) 109 ( Suppl. ) 241 - 241 2020年02月

ALT、γGTPの組み合わせによる糖尿病発症リスク評価の向上

宮森大輔, 田中希尚, 古橋眞人, 茂庭仁人, 三浦哲嗣, 小山雅之, 大西浩文, 沼田啓太, 久末章史, 塙なぎさ

日本内科学会雑誌 ( (一社)日本内科学会 ) 109 ( Suppl. ) 241 - 241 2020年02月

Differential regulation of hypoxanthine and xanthine by obesity in a general population.

Masato Furuhashi, Masayuki Koyama, Yukimura Higashiura, Takayo Murase, Takashi Nakamura, Megumi Matsumoto, Akiko Sakai, Hirofumi Ohnishi, Marenao Tanaka, Shigeyuki Saitoh, Norihito Moniwa, Kazuaki Shimamoto, Tetsuji Miura

Journal of diabetes investigation 11 ( 4 ) 878 - 887 2020年01月 [査読有り] [国内誌]

AIMS/INTRODUCTION: Uric acid is synthesized by oxidation of hypoxanthine and xanthine using a catalyzing enzyme, xanthine oxidoreductase (XOR), which can be a source of reactive oxygen species. Plasma XOR activity is a metabolic biomarker associated with obesity, hyperuricemia, liver dysfunction and insulin resistance. However, it has recently been reported that XOR activity in fat tissue is low in humans, unlike in rodents, and that hypoxanthine is secreted from human fat tissue. MATERIALS AND METHODS: The associations of obesity with hypoxanthine, xanthine and plasma XOR activity were investigated in 484 participants (men/women: 224/260) of the Tanno-Sobetsu Study. RESULTS: Levels of hypoxanthine, xanthine and plasma XOR activity were significantly higher in men than in women. In 59 participants with hyperuricemia, 11 (men/women: 11/0) participants were being treated with an XOR inhibitor and had a significantly higher level of xanthine, but not hypoxanthine, than that in participants without treatment. In all of the participants, hypoxanthine concentration in smokers was significantly higher than that in non-smokers. Stepwise and multivariate regression analyses showed that body mass index, smoking habit and xanthine were independent predictors of hypoxanthine after adjustment of age, sex and use of antihyperuricemic drugs. Whereas, alanine transaminase, hypoxanthine and plasma XOR activity were independent predictors for xanthine, and alanine transaminase, triglycerides and xanthine were independent predictors for plasma XOR activity. CONCLUSIONS: The concentration of hypoxanthine, but not that of xanthine, is independently associated with obesity and smoking habit, indicating differential regulation of hypoxanthine and xanthine in a general population.

一般住民においてヒポキサンチンとキサンチンの血中濃度は肥満によって異なった制御を受ける

古橋眞人, 東浦幸村, 小山雅之, 村瀬貴代, 中村敬志, 酒井晶子, 田中希尚, 茂庭仁人, 大西浩文, 斎藤重幸, 三浦哲嗣

日本痛風・核酸代謝学会総会プログラム抄録集 ( (一社)日本痛風・尿酸核酸学会 ) 53回 74 - 74 2020年01月

Forgetting to take antiseizure medications is associated with focal to bilateral tonic-clonic seizures, as revealed by a cross-sectional study.

Hime Suzuki, Nobuhiro Mikuni, Hirofumi Ohnishi, Rintaro Yokoyama, Rei Enatsu, Satoko Ochi

PloS one 15 ( 10 ) e0240082 2020年 [国際誌]

OBJECTIVES: To evaluate the effects of nonadherence to antiseizure medications (ASMs) and clinical characteristics on seizure control, we employed a prospective cohort cross-sectional study using self-reports and medical records of patients with epilepsy (PWEs). METHODS: Eight hundred and fifty-five PWEs taking ASMs were enrolled from fourteen collaborative outpatient clinics from January 2018 to March 2019. Questions from the Morisky Medication Adherence Scale were used as adherence self-reports. If a PWE's questionnaire indicated that they had missed doses of their ASMs, outpatient physicians asked them directly about the details of their compliance, including the timing of intentionally or unintentionally missed doses. The association between lack of seizure control and utilization outcomes, such as missed doses, demographics, and clinical characteristics of the PWEs, were assessed by univariate and multivariate analyses. RESULTS: Multivariate analysis revealed that forgetting to take ASMs was associated with lack of seizure control and the existence of focal to bilateral tonic-clonic seizures. Dementia, younger age, use of three or more antiepileptic agents, and living in a one-person household were associated with the risk of forgetting to take ASMs. SIGNIFICANCE: For PWEs with poor drug management or a high incidence of missed doses of ASMs, efforts to improve adherence could facilitate better seizure control and decrease focal to bilateral tonic-clonic propagation.

Lower limb muscle mass is associated with insulin resistance more than lower limb muscle strength in non-diabetic older adults.

Toshiaki Seko, Hiroshi Akasaka, Masayuki Koyama, Nobuaki Himuro, Shigeyuki Saitoh, Tetsuji Miura, Mitsuru Mori, Hirofumi Ohnishi

Geriatrics & gerontology international 19 ( 12 ) 1254 - 1259 2019年12月 [査読有り] [国内誌]

AIM: We examined the association of muscle mass and muscle strength with insulin resistance, focusing on lower limb muscles. METHODS: This was a cross-sectional study, and participants were registered in 2017 from the Tanno-Sobetsu Study, a population-based cohort study. After excluding individuals aged <64 years or with a history of diabetes mellitus, 272 non-diabetic older adults (116 men, 156 women) met the inclusion criteria. According to the homeostasis model assessment of insulin resistance, the participants were divided into two groups; that is, the insulin resistance group (homeostasis model assessment of insulin resistance ≥1.73) and non-insulin resistance group (homeostasis model assessment of insulin resistance <1.73). Muscle mass (lower limb, upper limb, appendicular and trunk) and muscle strength (grip strength and knee extension torque) were measured and divided by the weight, and then multiplied by 100 to calculate the weight ratio (%). The adjusted odds ratio (OR) of each muscle index for risk of insulin resistance was calculated separately for both men and women. RESULTS: Lower limb muscle mass (OR 0.72, 95% CI 0.55-0.92 in men; OR 0.69, 95% CI 0.51-0.96 in women, respectively) and appendicular muscle mass (OR 0.75, 95% CI 0.61-0.94 in men; OR 0.72, 95% CI 0.54-0.95 in women, respectively), but not other muscle indexes, were associated with risk of insulin resistance, after adjusting for age, body mass index, highly sensitive C-reacting protein and smoking habits. CONCLUSIONS: Lower limb muscle mass of non-diabetic older adults is independently related to insulin resistance. Geriatr Gerontol Int 2019; 19: 1254-1259.

Longitudinal impact of dapagliflozin treatment on ventricular repolarization heterogeneity in patients with type 2 diabetes.

Sato T, Miki T, Furukawa S, Matsuura B, Hiasa Y, Ohnishi H, Tanno M, Miura T

Journal of diabetes investigation 10 ( 6 ) 1593 - 1594 2019年11月 [査読有り] [国内誌]

一般住民において血漿ヒポキサンチン濃度は肥満度および喫煙と関連する

東浦幸村, 古橋眞人, 松本めぐみ, 酒井晶子, 小山雅之, 村瀬貴代, 中村敬志, 田中希尚, 茂庭仁人, 大西浩文, 斎藤重幸, 三浦哲嗣

肥満研究 ( (一社)日本肥満学会 ) 25 ( Suppl. ) 279 - 279 2019年10月

外国人患者の当院受療時ニーズに関する社会疫学的調査(第2報)

鈴村美和, 菅原誠, 鈴村滋生, 森満, 大西浩文

日本公衆衛生学会総会抄録集 ( 日本公衆衛生学会 ) 78回 589 - 589 2019年10月

一般住民におけるキサンチン酸化還元酵素(XOR)活性と高血圧との関連

東浦幸村, 古橋眞人, 小山雅之, 田中希尚, 茂庭仁人, 松本めぐみ, 酒井晶子, 村瀬貴代, 中村敬志, 大西浩文, 齋藤重幸, 島本和明, 三浦哲嗣

日本高血圧学会総会プログラム・抄録集 ( (NPO)日本高血圧学会 ) 42回 279 - 279 2019年10月

北海道都市部健診受診者コホートにおける初年度の血圧カテゴリ別の血清尿酸値と高血圧発症との関連

小山雅之, 樋室伸顕, 田中希尚, 茂庭仁人, 古橋眞人, 沼田啓太, 久末章史, 塙なぎさ, 齋藤重幸, 三浦哲嗣, 大西浩文

日本高血圧学会総会プログラム・抄録集 ( (NPO)日本高血圧学会 ) 42回 300 - 300 2019年10月

Annual change in plasma xanthine oxidoreductase activity is associated with changes in liver enzymes and body weight.

Masato Furuhashi, Masayuki Koyama, Megumi Matsumoto, Takayo Murase, Takashi Nakamura, Yukimura Higashiura, Marenao Tanaka, Norihito Moniwa, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

Endocrine journal 66 ( 9 ) 777 - 786 2019年09月 [査読有り] [国内誌]

Xanthine oxidoreductase (XOR), an enzyme of uric acid formation from hypoxanthine and xanthine, is recognized as a source of oxidative stress. Plasma activity of XOR has been reported to be a biomarker of metabolic disorders associated with obesity, liver dysfunction, insulin resistance, hyperuricemia and adipokines. We investigated longitudinal change in plasma XOR activity, which was determined by using mass spectrometry and liquid chromatography to detect [13C2, 15N2]-uric acid using [13C2, 15N2]-xanthine as a substrate, in 511 subjects (male/female: 244/267) of the Tanno-Sobetsu Study in the years 2016 and 2017. Plasma XOR activity in a basal state was significantly higher in men than in women, but no significant sex difference was observed in annual change in plasma XOR activity. Annual change in plasma activity of XOR was positively correlated with changes in each parameter, including body weight (r = 0.203, p < 0.001), body mass index, diastolic blood pressure, aspartate transaminase (AST) (r = 0.772, p < 0.001), alanine transaminase (r = 0.647, p < 0.001), γ-glutamyl transpeptidase, total cholesterol, triglycerides, uric acid, fasting glucose and HbA1c. Multivariate regression analysis demonstrated that change in AST and that in body weight were independent predictors of change in plasma XOR activity after adjustment of age, sex and changes in each variable with a significant correlation without multicollinearity. In conclusion, annual change in plasma XOR activity is independently associated with changes in liver enzymes and body weight in a general population. Improvement of liver function and reduction of body weight would decrease plasma XOR activity and its related oxidative stress as a therapeutic strategy.

Insulin Resistance is Associated with Longitudinal Changes of Cardiac Repolarization Heterogeneity in Apparently Healthy Subjects.

Tamaki Matsumoto, Hirofumi Ohnishi, Tatsuya Sato, Takayuki Miki, Hiroshi Akasaka, Nagisa Hanawa, Masayuki Koyama, Shigeyuki Saitoh, Tetsuji Miura

Cardiology and therapy 8 ( 2 ) 239 - 251 2019年07月 [査読有り] [国際誌]

INTRODUCTION: Increased heterogeneity in ventricular repolarization is a risk factor of sudden cardiac death, but its natural history is unclear. Here we examined whether insulin resistance is associated with longitudinal change in ventricular repolarization heterogeneity in apparently healthy subjects. METHODS: The study subjects were participants in health checkups in cohort 1 and cohort 2, which were followed up for 6 years and 5 years, respectively. Subjects with diabetes, cardiovascular disease, or renal disease at baseline were excluded from the analyses. As indices of insulin resistance, the homeostasis model assessment of insulin resistance (HOMA-IR) and triglyceride to HDL-cholesterol ratio (TG/HDL-C) were used in cohort 1 and cohort 2, respectively. Heterogeneity in ventricular repolarization was assessed by heart rate-corrected Tpeak-Tend interval in V5 (cTpTe), QT interval, and QT dispersion. In regression analyses, parameters with a skewed distribution were normalized by logarithmic transformation or by Box-Cox transformation. RESULTS: In longitudinal analyses, Box-Cox-transformed cTpTe at the end of follow-up was weakly correlated with log HOMA-IR at baseline in cohort 1 (n = 153, r = - 0.207, 95% CI - 0.354 to - 0.050, p = 0.010) and with log TG/HDL-C at baseline in cohort 2 (n = 738, r = - 0.098, 95% CI - 0.169 to - 0.026, p = 0.008). Multiple regression analysis showed that indices of insulin resistance, but not glycosylated hemoglobin (HbA1c) or plasma glucose, at baseline were significant explanatory variables for cTpTe at the end of follow-up. Neither QT interval nor QT dispersion was correlated with metabolic parameters. CONCLUSION: Insulin resistance may be involved in the longitudinal increase of ventricular repolarization heterogeneity in apparently healthy subjects.

日本の大規模コホートによる糖尿病と高血圧が心血管疾患による死亡の生涯リスクに与える影響 The EPOCH-JAPAN study

今井由希子, 平田匠, 斎藤重幸, 二宮利治, 宮本恵宏, 大西浩文, 磯博康, 三浦克之, 玉腰暁子, 山田美智子, 木山昌彦, 石川鎮清, 岡村智教

日本動脈硬化学会総会プログラム・抄録集 ( (一社)日本動脈硬化学会 ) 51回 2 - 5 2019年07月 [査読有り]

【診療ガイドラインの読み方ガイダンス】循環器領域での診療ガイドライン作成経験システマティックレビューチームの役割

樋室伸顕, 大西浩文

泌尿器外科 ( 医学図書出版(株) ) 32 ( 7 ) 927 - 931 2019年07月

高血圧治療ガイドライン2019の作成において、システマティックレビューチームの一員としてひとつのClinical Question(CQ)に対するシステマティックレビューを担当した。Mindsの「診療ガイドライン作成マニュアル」に従い作業を進めたが、スクリーニングは慎重な作業が求められ、エビデンス評価はその判定基準に悩むことが多い。一方CQに関する論文を網羅的に読むのでその分野の専門家になることができる。(著者抄録)

【JSH2019改訂における重要ポイント(3)糖尿病合併高血圧】降圧薬選択に関するシステマティックレビュー

大西浩文, 国村彩子, 樋室伸顕, 瀬川裕佳, 藤吉朗, 斎藤重幸

血圧 ( (株)先端医学社 ) 26 ( 7 ) 397 - 405 2019年07月

今回、高血圧治療ガイドライン2019の策定にあたって、「糖尿病合併高血圧の降圧治療では、Ca拮抗薬、サイアザイド系利尿薬よりも、ARB、ACE阻害薬を優先するべきか」を明らかにするためのシステマティックレビューおよびメタアナリシスをおこなった。16件のRCTに基づいて検討をおこなうと、死亡や心血管疾患イベント、腎機能障害リスク低減効果についてレニン・アンジオテンシン(RA)系阻害薬の他の薬剤に対する明らかな優位性は示されなかった。結果の解釈には注意を要するものの、糖尿病合併高血圧患者における第一選択薬としては、ARB、ACE阻害薬のみならず、Ca拮抗薬、サイアザイド系利尿薬も推奨され得ると考えられた。(著者抄録)

Independent links between plasma xanthine oxidoreductase activity and levels of adipokines.

Masato Furuhashi, Megumi Matsumoto, Takayo Murase, Takashi Nakamura, Yukimura Higashiura, Masayuki Koyama, Marenao Tanaka, Norihito Moniwa, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

Journal of diabetes investigation 10 ( 4 ) 1059 - 1067 2019年07月 [査読有り] [国内誌]

AIMS/INTRODUCTION: Xanthine oxidoreductase (XOR) is a rate-limiting enzyme that catalyzes uric acid formation in the purine metabolism, is involved in an increase in reactive oxygen species. Plasma XOR activity has been shown to be associated with obesity, smoking, liver dysfunction, hyperuricemia, dyslipidemia and insulin resistance. MATERIALS AND METHODS: The association between plasma XOR activity, measured by using liquid chromatography and mass spectrometry, and levels of adipokines, including adiponectin, fatty acid-binding protein 4 (FABP4) and fibroblast growth factor 21 (FGF21), was investigated in 282 participants (male/female: 126/156) of the Tanno-Sobetsu Study who were not taking medication. RESULTS: Women had lower plasma XOR activity than did men. Smoking habit was associated with increased activity. Plasma XOR activity was positively correlated with concentrations of FABP4 (r = 0.192, P < 0.001) and FGF21 (r = 0.208, P < 0.001), homeostasis model assessment of insulin resistance as an index of insulin resistance and uric acid, and was negatively correlated with adiponectin level (r = -0.243, P = 0.001). Multivariate regression analyses showed that levels of adiponectin, FABP4 and FGF21 were independent determinants of plasma XOR activity after adjusting age, sex, uric acid and homeostasis model assessment of insulin resistance. With additional adjustment of smoking habit, the level of FABP4, but not that of adiponectin or FGF21, remained as an independent predictor of plasma XOR activity. CONCLUSIONS: Plasma XOR activity was independently associated with levels of adipokines in a general population of individuals not taking medication.

The effects of renin–angiotensin system inhibitors on mortality, cardiovascular events, and renal events in hypertensive patients with diabetes: a systematic review and meta-analysis of randomized controlled trials

Kunimura A, Himuro N, Fujiyoshi A, Segawa H, Ohnishi H, Saitoh S

Hypertension Research 42 ( 5 ) 669 - 680 2019年04月 [査読有り] [国際誌]

Renin-angiotensin system (RAS) inhibitors are often used as a first-line treatment for hypertensive patients with diabetes because of purported benefits, such as reno-protection. However, there is no clear evidence for the superiority of RAS inhibitors to other classes of antihypertensives for clinically important outcomes in this population. We conducted a meta-analysis to assess whether RAS inhibitors are better than other classes of antihypertensives for reducing mortality, and cardiovascular and renal events in hypertensive patients with diabetes. From June to December 2017, we searched Medline, Cochrane Library, and the database of the Japan Medical Abstracts Society (ICHUSHI) for relevant published randomized controlled trials that directly compared the effects of RAS inhibitors to other classes of antihypertensives as first-line treatments for reducing adverse outcomes among hypertensive patients with diabetes. Our predetermined outcomes included all-cause death, cardiovascular death, incidence of cardiovascular disease, and renal dysfunction. We identified 16 trials, including a total of 35,052 patients. No significant benefits for RAS inhibitors were found compared to other classes of antihypertensives for all-cause death (relative risk (RR) 0.95, 95% confidence interval (CI) 0.85-1.05, p = 0.29), cardiovascular death (RR 0.84, 95% CI 0.68-1.04, p = 0.11), incidence of cardiovascular disease (RR 0.93, 95% CI 0.84-1.03, p = 0.16), and incidence of renal dysfunction (RR 0.91, 95% CI 0.77-1.06, p = 0.22). In conclusion, RAS inhibitors are not superior to other classes of antihypertensive drugs for reducing all-cause and cardiovascular mortalities, cardiovascular events, and renal events in hypertensive patients with diabetes.

2型糖尿病患者の心筋再分極不均一に対するdapagliflozinの経時的効果

佐藤達也, 大西浩文, 三木隆幸, 古川慎哉, 松浦文三, 日浅陽一, 三浦哲嗣

糖尿病 ( (一社)日本糖尿病学会 ) 62 ( Suppl.1 ) S - 228 2019年04月

心血管イベントに対する高リスク糖尿病患者を検出するためのECG検査の重要性とSGLT2阻害剤による利点

三木隆幸, 佐藤達也, 大西浩文, 矢野俊之, 中田圭, 丹野雅也, 三浦哲嗣

日本循環器学会学術集会(Web) ( (一社)日本循環器学会 ) 83回 SY12 - 3 2019年03月

Effects of Hemosiderosis on Epilepsy Following Subarachnoid Hemorrhage.

Tsukasa Hirano, Rei Enatsu, Satoshi Iihoshi, Takeshi Mikami, Toshimi Honma, Hirofumi Ohnishi, Nobuhiro Mikuni

Neurologia medico-chirurgica 59 ( 1 ) 27 - 32 2019年01月 [国内誌]

Epilepsy after aneurysmal subarachnoid hemorrhage (post-SAH epilepsy) is a critical complication that influences clinical and social prognoses. However, the underlying mechanisms remain unclear. We investigated the relationship between hemosiderosis and the incidence of post-SAH epilepsy. About 50 patients with aneurysmal SAH who were admitted to Sapporo Medical University and Oji General Hospital between April 2010 and June 2016 were enrolled in this retrospective study. Hemosiderosis detected by T2*-weighted magnetic resonance imaging(MRI) and the incidence of post-SAH epilepsy were retrospectively analyzed. Post-SAH epilepsy was defined as an unprovoked seizures occurring more than 1 week after the onset of SAH. Six patients (12%) developed post-SAH epilepsy. In all patients, hemosiderosis in the cortex or cerebral parenchyma was detected by T2*-weighted MRI. Statistical analyses revealed that hemosiderosis and the co-existence of intracerebral hemorrhage (ICH) related with post-SAH epilepsy (Fisher's exact test, univariate exact logistic regression analysis: P < 0.05). Post-SAH epilepsy was predicted by hemosiderosis and the co-existence of ICH. The present results suggest that hemosiderin is the principal cause of post-SAH epilepsy and may be a predictor of this critical complication.

Lifetime Risk of Stroke and Coronary Heart Disease Deaths According to Blood Pressure Level: EPOCH-JAPAN (Evidence for Cardiovascular Prevention From Observational Cohorts in Japan)

Satoh M, Ohkubo T, Asayama K, Murakami Y, Sugiyama D, Yamada M, Saitoh S, Sakata K, Irie F, Sairenchi T, Ishikawa S, Kiyama M, Ohnishi H, Miura K, Imai Y, Ueshima H, Okamura T, EPOCH-JAPAN Research Group

Hypertension (Dallas, Tex. : 1979) 73 ( 1 ) 52 - 59 2019年01月 [査読有り] [国際誌]

Lifetime risk (LTR) provides an absolute risk assessment during the remainder of one’s life. Few studies have focused on the LTRs of stroke and coronary heart disease (CHD), categorized by fine blood pressure in Asian populations. We aimed to assess it using a large database of a meta-analysis with the individual participant data. The present metaanalysis included 107 737 Japanese (42.4% men; mean age, 55.1 years) from 13 cohorts. During the mean follow-up of 15.2±5.3 years (1 559 136 person-years), 1922 died from stroke and 913 from CHD. We estimated risks after adjusting for competing risk of death other than the outcome of interest. The 10-year risk of stroke and CHD deaths at index age of 35 years was ≤1.9% and ≤0.3%, respectively. The LTRs of stroke death at the index age of 35 years (men/women) were 6.1%/4.8% for optimal, 5.7%/6.3% for normal, and 6.6%/6.0% for high-normal blood pressure groups, and 9.1%/7.9% for grade 1, 14.5%/10.3% for grade 2, and 14.6%/14.3% for grade 3 hypertension groups. The LTRs of CHD death similarly elevated with an increase in blood pressure but were lower (≤7.2%) than those of stroke death. In conclusion, blood pressure was clearly associated with an elevated LTR of stroke or CHD death, although the LTR of CHD death was one-half of that of stroke death in an Asian population. These results would help young people with hypertension to adopt a healthy lifestyle or start antihypertensive therapy early.

Unexpected high plasma xanthine oxidoreductase activity in female subjects with low levels of uric acid.

Masato Furuhashi, Kazuma Mori, Marenao Tanaka, Takuto Maeda, Megumi Matsumoto, Takayo Murase, Takashi Nakamura, Masayuki Koyama, Norihito Moniwa, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

Endocrine journal 65 ( 11 ) 1083 - 1092 2018年11月 [査読有り] [国内誌]

Hypouricemia is a high-risk factor of exercise-induced acute kidney injury (EIAKI) probably through a lack of an antioxidant effect of uric acid. Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the formation of uric acid from hypoxanthine and xanthine, leading to an increase in superoxide and reactive oxygen species. Activation of XOR has been proposed to promote oxidative stress-related tissue injury. We measured plasma XOR activity by a sensitive and accurate assay using a combination of liquid chromatography and triple quadrupole mass spectrometry in subjects with relatively low levels of uric acid (≤4.0 mg/dL) who were recruited from 627 subjects (male/female: 292/335) in the Tanno-Sobetsu Study, a population-based cohort. The numbers of subjects with uric acid ≤4.0 mg/dL, ≤3.0 mg/dL and ≤2.0 mg/dL were 72 (11.5%, male/female: 5/67), 13 (2.1%, all females) and 2 (0.3%, both females), respectively. Plasma XOR activities in 5 male subjects were below the median value of the 292 male subjects. In 12 (17.9%) of the 67 female subjects with uric acid ≤4.0 mg/dL, plasma XOR activities were above the upper quartile value of the 335 female subjects. Eleven of the 12 female subjects with high plasma XOR activity and a low uric acid level had liver dysfunction and/or insulin resistance. In conclusion, unexpected high plasma XOR activities were found in some female subjects with relatively low levels of uric acid. Measurement of plasma XOR activity may help to identify hypouricemic patients with a high risk for EIAKI.

Association of Environmental Tobacco Smoke with the Risk of Severe Early Childhood Caries among 3-Year-Old Japanese Children.

Nakayama Y, Ohnishi H, Mori M

Caries research 53 ( 3 ) 268 - 274 2018年10月 [査読有り]

"多様性インスリン作用不全症候群"の意義及び評価と対策非糖尿病高齢者における下肢の筋量および筋力とインスリン抵抗性の関連

世古俊明, 赤坂憲, 樋室伸顕, 齋藤重幸, 三浦哲嗣, 大西浩文

糖尿病合併症 ( (一社)日本糖尿病合併症学会 ) 32 ( Suppl.1 ) 326 - 326 2018年10月

外国人患者の当院受療時ニーズに関する社会疫学的調査(第1報)

鈴村美和, 菅原誠, 鈴村滋生, 森満, 大西浩文

日本公衆衛生学会総会抄録集 ( 日本公衆衛生学会 ) 77回 583 - 583 2018年10月

地域一般住民におけるサルコペニアの頻度と表現型端野・壮瞥町研究

赤坂憲, 杉本研, 藤本拓, 高橋利匡, 大西浩文, 齋藤重幸, 樂木宏実

日本老年医学会雑誌 ( (一社)日本老年医学会 ) 55 ( 4 ) 713 - 713 2018年10月

Reliability and Validity of Hip Extensor Strength Measurement in Sitting Position by a Handheld Dynamometer in the Older Adults.

Seko T, Mori M, Ohnishi H, Himuro N, Takahashi Y, Kumamoto T, Ito T

Journal of geriatric physical therapy (2001) ( Ovid Technologies (Wolters Kluwer Health) ) 42 ( 4 ) E39 - E44 2018年08月 [査読有り]

Plasma Xanthine Oxidoreductase Activity as a Novel Biomarker of Metabolic Disorders in a General Population.

Masato Furuhashi, Megumi Matsumoto, Marenao Tanaka, Norihito Moniwa, Takayo Murase, Takashi Nakamura, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

Circulation journal : official journal of the Japanese Circulation Society 82 ( 7 ) 1892 - 1899 2018年06月 [査読有り] [国内誌]

BACKGROUND: Xanthine oxidoreductase (XOR) is an enzyme that catalyzes the formation of uric acid from hypoxanthine and xanthine, leading to an increase in superoxide and reactive oxygen species. Activation of XOR promotes oxidative stress-related tissue injury. We investigated the associations between metabolic parameters and plasma XOR activity measured by a sensitive and accurate assay using a combination of liquid chromatography and triple quadrupole mass spectrometry to detect [13C2,15N2]-uric acid using [13C2,15N2]-xanthine as a substrate.Methods and Results:A total of 627 Japanese subjects (M/F, 292/335) from the Tanno-Sobetsu Study, a population-based cohort, were recruited. Plasma XOR activity was significantly higher in males than in females, and habitual smoking was associated with elevation of activity. Plasma XOR activity was positively correlated with body mass index (BMI; r=0.323, P<0.001), waist circumference, blood pressure, and levels of liver enzymes including alanine transaminase (r=0.694, P<0.001), uric acid (r=0.249, P<0.001), triglycerides (r=0.312, P<0.001), hemoglobin A1c, fasting glucose, insulin and HOMA-R (r=0.238, P<0.001) as a marker of insulin resistance and was negatively correlated with high-density lipoprotein cholesterol level. On stepwise and multivariate regression analyses, BMI, smoking and levels of alanine transaminase, uric acid, triglycerides and HOMA-R were independent predictors of plasma XOR activity after adjustment for age and gender. CONCLUSIONS: Plasma XOR activity is a novel biomarker of metabolic disorders in a general population.

Interleukin-13 receptor alpha 2 as a marker of poorer prognosis in high-grade astrocytomas

Masahiko Wanibuchi, Yuko Kataoka-Sasaki, Masanori Sasaki, Shinichi Oka, Yayoi Otsuka, Miki Yamaguchi, Hirofumi Ohnishi, Shunya Ohtaki, Shouhei Noshiro, Satoshi Ookawa, Takeshi Mikami, Nobuhiro Mikuni, Osamu Honmou

Journal of Neurosurgical Sciences ( Edizioni Minerva Medica ) 62 ( 3 ) 239 - 244 2018年06月 [査読有り]

BACKGROUND: Interleukin-13 receptor alpha 2 (IL13Rα2) is considered a prognostic marker for gliomas according to the World Health Organization (WHO) grade. However, the expression levels of the marker vary from case to case, even within the same grade. We investigated whether IL13Rα2 could serve as a predictor of poorer prognosis in gliomas. METHODS: mRNA expression of IL13Rα2 was measured using real-time quantitative reverse transcription polymerase chain reaction (qRTPCR) in 52 formalin-fixed paraffin-embedded glioma samples (4 pilocytic astrocytomas, 9 diffuse astrocytomas, 12 anaplastic astrocytomas, and 27 glioblastomas, grade IV). The expression levels were compared with regard to WHO grade, MIB-1 index, patient's age, and overall survival. RESULTS: Real time qRT-PCR showed that IL13Rα2 is expressed in a subset of cases with a progressive increase from low- To high-grade astrocytomas (HGAs). The expression had a significant positive correlation with the MIB-1 index and advanced patient age at diagnosis. The overall survival (OS) of patients who had HGAs with higher levels of IL13Rα2 expression was significantly lower than the OS of those with HGAs with lower levels of IL13Rα2. In the 39 HGA cases studied, the median survival benefit in the lower expression group was 167.4 months. The median OS (mOS) in HGA group with lower IL13Rα2 expression was 186.4 months, while the mOS in the group with higher IL13Rα2 expression was 18.6 months (P=0.033). The hazard ratio, adjusted by fitting the Cox proportional hazard models for the mOS in the HGAs with higher IL13Rα2 levels and the HGGs with lower IL13Rα2 levels, was 5.97 (95% CI: 1.76 to 20.32). CONCLUSIONS: The results showed that IL13Rα2 may be used as a marker of poorer prognosis in HGAs, even among tumors of the same grade.

Nutritional Status and Energy Intake as Predictors of Functional Status After Cardiac Rehabilitation in Elderly Inpatients With Heart Failure ― A Retrospective Cohort Study ―

Satoshi Katano, Akiyoshi Hashimoto, Katsuhiko Ohori, Ayako Watanabe, Remi Honma, Rimi Yanase, Tomoyuki Ishigo, Takefumi Fujito, Hirofumi Ohnishi, Kazufumi Tsuchihashi, Sumio Ishiai, Tetsuji Miura

Circulation Journal ( Japanese Circulation Society ) 82 ( 6 ) 1584 - 1591 2018年05月 [査読有り]

降圧薬選択に関するシステマティックレビューから言えること

大西浩文, 樋室伸顕, 国村彩子, 瀬川裕佳, 藤吉朗

日本高血圧学会臨床高血圧フォーラムプログラム・抄録集 ( (NPO)日本高血圧学会 ) 7回 103 - 103 2018年05月

経口ブドウ糖負荷試験におけるブドウ糖曲線下面積と糖尿病発症との関連

世古俊明, 樋室伸顕, 赤坂憲, 齋藤重幸, 三浦哲嗣, 大西浩文

日本循環器病予防学会誌 ( (一社)日本循環器病予防学会 ) 53 ( 2 ) 182 - 182 2018年05月

一般住民における尿酸低値例での血漿キサンチン酸化還元酵素(XOR)活性の検討

森和真, 古橋眞人, 田中希尚, 村瀬貴代, 中村敬志, 前田卓人, 大西浩文, 三浦哲嗣

日本腎臓学会誌 ( (一社)日本腎臓学会 ) 60 ( 3 ) 365 - 365 2018年04月

脂肪酸結合タンパク4(FABP4)濃度は動脈硬化進展度の予測因子である

古橋眞人, 湯田聡, 村中敦子, 川向美奈, 松本めぐみ, 田中希尚, 茂庭仁人, 大西浩文, 斎藤重幸, 三浦哲嗣

糖尿病 ( (一社)日本糖尿病学会 ) 61 ( Suppl.1 ) S - 319 2018年04月

Circulating Fatty Acid-Binding Protein 4 Concentration Predicts the Progression of Carotid Atherosclerosis in a General Population Without Medication.

Masato Furuhashi, Satoshi Yuda, Atsuko Muranaka, Mina Kawamukai, Megumi Matsumoto, Marenao Tanaka, Norihito Moniwa, Hirofumi Ohnishi, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

Circulation journal : official journal of the Japanese Circulation Society 82 ( 4 ) 1121 - 1129 2018年03月 [査読有り] [国内誌]

BACKGROUND: Fatty acid-binding protein 4 (FABP4), which is expressed in both adipocytes and macrophages, is secreted from the cells and acts as an adipokine. An elevated circulating FABP4 level is associated with insulin resistance and atherosclerosis.Methods and Results:We investigated the causative association between FABP4 level and progression of atherosclerosis in subjects of the Tanno-Sobetsu Study, a population-based cohort. In 281 subjects without medication (male/female: 109/172) in the year 2010 or 2013, the carotid intima-media thickness (CIMT) assessed using carotid ultrasonography was significantly correlated with age, adiposity, blood pressure, renal dysfunction and levels of cholesterol, triglycerides, fasting glucose, HbA1c and FABP4 (r=0.331, P<0.001). Multiple regression analysis demonstrated that age, sex and FABP4 concentration were independent predictors of CIMT. A total of 78 (male/female: 29/49) of the 156 subjects in 2010 underwent carotid ultrasonography again in 2013. The change in CIMT each year during that 3-year period (mean±SD: 3.8±22.3 µm/year) was positively correlated with basal levels of high-sensitivity C-reactive protein (hsCRP) (r=0.231, P=0.046) and FABP4 (r=0.267, P=0.018) in 2010. After adjustment for age, sex and hsCRP level, the basal FABP4 level was independently associated with the change in CIMT per year. CONCLUSIONS: FABP4 concentration is an independent predictor of the progression of carotid atherosclerosis.

糖尿病や検尿異常のない場合もLDL-コレステロール高値はCKDの危険因子となる

長南新太, 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

日本内科学会雑誌 ( (一社)日本内科学会 ) 107 ( Suppl. ) 252 - 252 2018年02月

Distinct impacts of sleep-disordered breathing on glycemic variability in patients with and without diabetes mellitus

Kei Nakata, Takayuki Miki, Masaya Tanno, Hirofumi Ohnishi, Toshiyuki Yano, Atsuko Muranaka, Tatsuya Sato, Hiroto Oshima, Yuki Tatekoshi, Masashi Mizuno, Koki Abe, Tetsuji Miura

PLOS ONE ( PUBLIC LIBRARY SCIENCE ) 12 ( 12 ) e0188689 2017年12月 [査読有り]

Background Sleep-disordered breathing (SDB) is highly prevalent in patients with diabetes mellitus (DM) and heart failure (HF) and contributes to poor cardiovascular outcomes. Enlarged glycemic variability (GV) is a risk factor of cardiac events independently of average blood glucose level, but the influence of SDB on GV is uncertain. In this study, we examined whether the impact of SDB on GV is modified by the presence of DM with or without HF. Methods and results Two hundred three patients (67.5 +/- 14.1 [ SD] years old, 132 males) who were admitted to our institute for examination or treatment of DM and/or HF underwent continuous glucose monitoring and polysomnography. Both HbA1c (8.0 +/- 2.0 vs. 5.7 +/- 0.4%) and mean amplitude of glycemic excursion (MAGE, median: 95.5 vs. 63.5 mg/dl) were significantly higher in a DM group (n = 100) than in a non-DM group (n = 103), but apnea-hypopnea index (AHI: 29.0 +/- 22.7 vs. 29.3 +/- 21.5) was similar in the two groups. AHI was correlated with log MAGE in the non-DM group but not in the DM group, and multivariate regression analysis revealed that AHI was an independent variable for log MAGE in the non-DM group but not in the DM group. We then divided the non-DM patients into two subgroups according to BNP level (100 pg/ml). AHI was positively correlated with log MAGE (r = 0.74, p<0.001) in the non-DM low-BNP subgroup, but such a correlation was not found in the non-DM high-BNP subgroup. Continuous positive airway pressure (CPAP) reduced MAGE from 75.3 to 53.0 mg/dl in the non-DM group but did not reduce MAGE in the DM group. Conclusion Severity of SDB was associated with higher GV, but DM as well as HF diminished the contribution of SDB to GV. Treatment with CPAP was effective for reduction of GV only in patients without DM.

Surfactant protein D inhibits activation of non-small cell lung cancer-associated mutant EGFR and affects clinical outcomes of patients

Y. Umeda, Y. Hasegawa, M. Otsuka, S. Ariki, R. Takamiya, A. Saito, Y. Uehara, H. Saijo, K. Kuronuma, H. Chiba, H. Ohnishi, Y. Sakuma, H. Takahashi, Y. Kuroki, M. Takahashi

Oncogene ( Nature Publishing Group ) 36 ( 46 ) 6432 - 6445 2017年11月 [査読有り]

Tyrosine kinase inhibitor (TKI)-sensitive and TKI-resistant mutations of epidermal growth factor receptor (EGFR) are associated with lung adenocarcinoma. EGFR mutants were previously shown to exhibit ligand-independent activation. We have previously demonstrated that pulmonary surfactant protein D (SP-D, SFTPD) suppressed wild-type EGFR signaling by blocking ligand binding to EGFR. We herein demonstrate that SFTPD downregulates ligand-independent signaling in cells harboring EGFR mutations such as TKI-sensitive exon 19 deletion (Ex19del) and L858R mutation as well as TKI-resistant T790M mutation, subsequently suppressing cellular growth and motility. Lectin blotting and ligand blotting in lung cancer cell lines suggested that EGFR mutants express oligomannose-type N-glycans and interact with SFTPD directly. Cross-linking assay indicated that SFTPD inhibits ligand-independent dimerization of EGFR mutants. We also demonstrated that SFTPD reduced dimerization-independent phosphorylation of Ex19del and T790M EGFR mutants using point mutations that disrupted the asymmetric dimer interface. It was confirmed that SFTPD augmented the viability-suppressing effects of EGFR-TKIs. Furthermore, retrospective analysis of 121 patients with lung adenocarcinoma to examine associations between serum SFTPD levels and clinical outcome indicated that in TKI-treated patients with lung cancer harboring EGFR mutations, including Ex19del or L858R, high serum SFTPD levels correlated with a lower number of distant metastases and prolonged overall survival and progression-free survival. These findings suggest that SFTPD downregulates both TKI-sensitive and -resistant EGFR mutant signaling, and SFTPD level is correlated with clinical outcome. These findings illustrate the use of serum SFTPD level as a potential marker to estimate the efficacy of EGFR-TKIs.

Effect of sodium-glucose co-transporter-2 inhibitors on impaired ventricular repolarization in people with Type 2 diabetes

T. Sato, T. Miki, H. Ohnishi, T. Yamashita, A. Takada, T. Yano, M. Tanno, A. Tsuchida, T. Miura

Diabetic Medicine ( Blackwell Publishing Ltd ) 34 ( 10 ) 1367 - 1371 2017年10月 [査読有り]

Aims: To test the hypothesis that treatment with a sodium-glucose co-transporter-2 inhibitor would reverse ventricular repolarization heterogeneity, a predictor of cardiovascular mortality, in people with Type 2 diabetes. Methods: We retrospectively analysed changes in indices of ventricular repolarization before and after treatment with a sodium-glucose co-transporter-2 inhibitor in 46 people with Type 2 diabetes. Results: Sodium-glucose co-transporter-2 inhibitor treatment reduced HbA1c concentration [62±13 mmol/mol (7.7±1.2%) vs 59±16 mmol/mol (7.5±1.4%)], body weight (77.8±13.9 vs 74.7±12.5 kg) and systolic blood pressure (133±18 vs 126±12 mmHg) in the study participants. Heart rate and QTc interval were not changed by sodium-glucose co-transporter-2 inhibitor treatment, but QTc dispersion was significantly reduced (median, 48.8 vs 44.2 ms). Sodium-glucose co-transporter-2 inhibitor treatment reversed QTc dispersion more in participants who had larger QTc dispersion before the treatment. Changes in systolic blood pressure (Spearman's ρ= 0.319 P=0.031), but not in HbA1c concentration, were correlated with changes in QTc dispersion after sodium-glucose co-transporter-2 inhibitor treatment. Conclusions: The findings suggest that sodium-glucose co-transporter-2 inhibitor treatment reverses ventricular repolarization heterogeneity in people with Type 2 diabetes, independently of its effect on glycaemic control. The favourable effect on ventricular repolarization heterogeneity could be the mechanism by which empaglifozin reduced cardiovascular events in a recent study.

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.

Prevalence and clinical characteristics of degenerative mitral stenosis

Yasuyuki Ukita, Satoshi Yuda, Hideaki Sugio, Ayaka Yonezawa, Yuka Takayanagi, Hitomi Masuda-Yamamoto, Node Tanaka-Saito, Hirofumi Ohnishi, Tetsuji Miura

JOURNAL OF CARDIOLOGY ( ELSEVIER SCIENCE BV ) 68 ( 3-4 ) 248 - 252 2016年09月 [査読有り]

Background: Degenerative mitral stenosis (DMS) is found in the elderly population. However, there are a few reports regarding the prevalence rate of DMS and, its clinical characteristics. The aim of this study was to determine the relationship between age, gender, and the prevalence rate of DMS. Methods: Patients with DMS and rheumatic mitral stenosis (RMS) were searched retrospectively in consecutive patients who underwent echocardiography from January 2011 to December 2013 in a community hospital. DMS was defined as presence of both turbulent antegrade flow with a mean transmitral pressure gradient (PG) of >= 2 mmHg and mitral annular calcification without restriction of leaflets tip motion. Results: We identified 19 patients (17 female and 2 male) with DMS (0.22%) and 19 patients with RMS in 8683 patients. The prevalence rate of DMS significantly increased with aging, especially in patients >90 years old. There was no significant difference in the prevalence rates of RMS among the age groups. Patients with DMS were older (86 +/- 8 years vs. 73 +/- 10 years, p < 0.01) and had higher rates of hypertension and aortic stenosis, larger left ventricular mass index, and mean PG of aortic valve, smaller aortic valve area, less degree of left atrial dilatation, and lower rate of atrial fibrillation, compared with those values in patients with RMS. Conclusions: DMS is rare (0.22%) and almost exclusively found in females in routine echocardiography. The prevalence of DMS increases with aging to 2.5% in patients >90 years of age, and DMS is often associated with aortic valve stenosis. (C) 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Pulmonary vascular resistance estimated by Doppler echocardiography predicts mortality in patients with interstitial lung disease

Kenji Yasui, Satoshi Yuda, Kiyoshi Abe, Atsuko Muranaka, Mitsuo Otsuka, Hirofumi Ohnishi, Akiyoshi Hashimoto, Hiroki Takahashi, Kazufumi Tsuchihashi, Hiroki Takahashi, Satoshi Takahashi, Tetsuji Miura

JOURNAL OF CARDIOLOGY ( ELSEVIER SCIENCE BV ) 68 ( 3-4 ) 300 - 307 2016年09月 [査読有り]

Background: Pulmonary hypertension (PH) is a strong predictor of mortality in patients with interstitial lung disease (ILD). However, patients with ILD often have poor outcomes even in the absence of PH. Pulmonary vascular resistance (PVR) assessed by right heart catheterization is a predictor of mortality in patients with ILD. However, the clinical utility of PVR assessed by Doppler echocardiography (PVRecho) as a predictor of the outcome in patients with ILD remains unclear. The aim of this study was to examine whether PVRecho independently predicts mortality in patients with ILD. Methods: Echocardiographic examinations were performed in 133 consecutively enrolled patients with ILD (age, 67 +/- 9 years; 53% men). Tricuspid annular plane systolic excursion (TAPSE) was measured, and PVRecho was calculated by the following formula: PVRecho = [TRV x 10/time-velocity integral of right ventricular outflow (RVOT-VTI)] + 0.16. Data for parameters of pulmonary functional tests and for serum biomarkers, which were measured within 3 months before or after the echocardiographic examinations, were collected. Results: During a mean follow-up period of 18 +/- 7 months, 13 patients died due to respiratory failure (n = 10), heart failure (n = 1), or unknown causes (n = 2). In univariate analysis, body mass index, idiopathic pulmonary fibrosis, use of an antifibrotic drug (AD), RVOT-VTI, PVRecho, percentage of predicted vital capacity (%VC), percentage of predicted forced expiratory volume in 1 second, and percentage of predicted diffusion capacity of the lungs for carbon monoxide (%DLco), but not TAPSE or serum biomarkers, were significantly associated with mortality. Cox proportional hazard multivariate analysis indicated that %VC [hazard ratio (HR): 0.92, p = 0.001], use of AD (HR: 4.05, p = 0.043), and PVRecho (HR: 3.79, p = 0.029) independently predict mortality in patients with ILD. Replacement of %VC with %DLco in the multivariate analysis did not change the results: %DLco (HR: 0.90, p = 0.001), use of AD (HR: 7.53, p = 0.029), and PVRecho (HR: 3.65, p = 0.020). Conclusions: In addition to parameters of pulmonary function tests and use of AD, increased PVRecho is an independent predictor of mortality in patients with ILD who were evaluated for screening of PH by echocardiography. (C) 2016 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

Independent Link Between Levels of Proprotein Convertase Subtilisin/Kexin Type 9 and FABP4 in a General Population Without Medication

Masato Furuhashi, Akina Omori, Megumi Matsumoto, Yu Kataoka, Marenao Tanaka, Norihito Moniwa, Hirofumi Ohnishi, Hideaki Yoshida, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

AMERICAN JOURNAL OF CARDIOLOGY ( EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC ) 118 ( 2 ) 198 - 203 2016年07月 [査読有り]

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to and degrades the low density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Fatty acid binding protein 4 (FABP4/adipocyte FABP/aP2) is secreted from adipocytes in association with lipolysis, and circulating FABP4 has been reported to act as an adipokine for the development of insulin resistance and atherosclerosis. Elevated serum FABP4 level is associated with obesity, insulin resistance, dyslipidemia, and atherosclerosis. In this study, we examined the association between circulating levels of FABP4 and PCSK9 in a general population. A total of 265 subjects (male/female: 98/167) who were not on medication were recruited from subjects of the Tanno-Sobetsu Study, and concentrations of FABP4 and PCSK9 were measured. The level of FABP4, but not that of PCSK9, showed a gender difference, being higher in women than in men. FABP4 level was independently associated with gender, adiposity, renal dysfunction, and levels of cholesterol and PCSK9. There was a significant and gender different correlation between PCSK9 level and age: negatively in men (r = 0.250, p = 0.013) and positively in women (r = 0.183, p = 0.018). After adjustment of age, gender, and LDL cholesterol level, PCSK9 level was positively and independently correlated with FABP4 concentration. In conclusion, PCSK9 level is differentially regulated by gender during aging. Circulating FABP4 is independently associated with the PCSK9 level, suggesting that elevation of FABP4 level as an adipokine leads to dyslipidemia through increased PCSK9 level and subsequent degradation of the LDL receptor. (C) 2016 Elsevier Inc. All rights reserved.

Double balloon protection during carotid artery stenting for vulnerable carotid stenosis reduces the incidence of new brain lesions

Masahito Nakazaki, Tadashi Nonaka, Akira Takahashi, Yasuyuki Yonemasu, Tatsufumi Nomura, Toshiyuki Onda, Osamu Honda, Yuji Hashimoto, Hirofumi Ohnishi, Masanori Sasaki, Masahiko Daibo, Osamu Honmou

ACTA NEUROCHIRURGICA ( SPRINGER WIEN ) 158 ( 7 ) 1377 - 1386 2016年07月 [査読有り]

The use of distal filter protection alone is associated with a high risk of ischemic complications when vulnerable carotid stenosis is treated by carotid artery stenting (CAS). Double balloon protection, a combination of distal balloon protection and proximal balloon occlusion, can be utilized. We assessed the outcome and complications of the double balloon protection method for vulnerable carotid stenosis. Among 130 patients who underwent CAS from 2009 to 2014, we enrolled the following patients: those whose target lesion was vulnerable as evaluated by MRI, i.e., a signal ratio of plaque to posterior cervical muscle on T1-weighted images before CAS of a parts per thousand yen1.5, and those who underwent diffusion-weighted imaging (DWI) studies within 48 h after the procedure. Ninety patients were enrolled. We investigated DWI findings of the double balloon protection group compared with those of the simple distal balloon protection and distal filter protection groups. Sixty-four patients (71 %) underwent double balloon protection, 15 patients (17 %) simple distal balloon protection, and 11 patients (12 %) distal filter protection. Symptomatic embolic complications and new lesions on DWI after CAS were significantly less common in patients undergoing double balloon protection compared to distal balloon protection or distal filter protection (0 % vs. 20 %, 9 %, P < 0.01, and 30 % vs. 67 %, 82 %, P < 0.01, respectively). Logistic regression analysis also identified the odds ratio of double balloon protection for new lesions on DWI after CAS of 0.23 (95 % confidence interval: 0.07-0.70, P < 0.01) compared to simple distal protections. In the patients who underwent CAS for vulnerable carotid stenosis, double balloon protection was an independent significant factor associated with a reduction in the risk of new lesions on DWI after the procedure compared to conventional distal protections.

Analysis of resources assisting in coping with swallowing difficulties for patients with Parkinson's disease: a cross-sectional study

Aiko Matsushima, Junichi Matsushima, Akihisa Matsumoto, Fumio Moriwaka, Sanae Honma, Kazunori Itoh, Keiko Yamada, Shun Shimohama, Hirofumi Ohnishi, Mitsuru Mori

BMC HEALTH SERVICES RESEARCH ( BIOMED CENTRAL LTD ) 16 276 2016年07月 [査読有り]

Background: Malnutrition induced by swallowing difficulties (SD) impairs the quality of life and gives rise to SD-related costs in Parkinson's disease (PD) patients. With results of a swallowing difficulty questionnaire and data of resources specifically obtained such as SD-related costs, caregivers, and dietary therapies, this study is to suggest statistically supported ideas for improvements in arrangements for how participants cope with SD and maintain general well-being. Methods: We interviewed 237 PD patients. The SD-related costs involved those incurred by the provision of dietary modifications, care oriented foods, alternatives, and supplements. Dietary therapies included rice porridge and commercially available care foods. The relationships between BMI (body mass index) and the severity of SD assumed in this paper as indicators for general well-being and as resources for coping with SD for PD patients were statistically analyzed. Results: A lower BMI was found in participants eating porridge consistency rice (p = 0.003) and eating porridge rice is significantly related to the severity of SD (p < 0.0001) and PD (p = 0.002). The severity of SD increased with age and PD duration (p = 0.035, p = 0.0005). Outlays for dietary modifications are the lowest reported here (p < 0.004) but the number of participants using dietary modifications is the largest among the SD-related items (n = 58). Eating care foods were reported for 11 older participants (p < 0.0001), most female (10/11). No lower BMI was found in participants eating care foods when compared with participants eating ordinary foods. Dietary modifications were performed by caregivers (OR: 6.8, CI: 3.1-15.2, p < 0.0001) and were related to the presence of children (OR: 3.4, CI: 1.2-11.4. p = 0.024). Older participants commonly live with spouses and children. Conclusions: Severe SD is associated with higher costs of coping with SD. A lower BMI is associated with modified foods, mostly eaten to cope with SD. Presence of caregivers and other persons residing with the participants here are related to dietary modifications but not to care food-related costs. Care foods may be effective in preventing malnutrition although the number who are able to cover the added expenses is limited because of the higher prices and shortage of information on the usefulness of care foods.

Combination of type 2 diabetes and smoking increases total cancer mortality in Japanese men using competing risk analysis: the Tanno-Sobetsu study

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

Diabetology International ( Springer Tokyo ) 7 ( 2 ) 167 - 172 2016年06月 [査読有り]

Aims: We assessed the impact of the combination of type 2 diabetes (T2DM) and smoking on total cancer mortality using cohort data of a general Japanese population. Methods: Of 1908 residents who received health checkups in two towns in 1994, 794 males were included as study participants. Smoking status was defined as three categories: never smoker, ex-smoker and current smoker. Individuals with T2DM were defined as individuals with fasting plasma glucose ≥7.0 mmol/l and/or receiving medication for T2DM. Participants were divided into six groups according to T2DM and smoking status: non-DM (NDM) and never smoker, NDM and ex-smoker, NDM and current smoker, DM and never smoker, DM and ex-smoker, and DM and current smoker groups. All participants were followed up for a maximum of 13 years. We calculated the hazard ratio (HR) using Cox’s proportional hazard model and subhazard ratio (SHR) using competing risk regression analyses in each group. Results: During the follow-up period, there were 169 all-cause deaths (62 cancer deaths and 40 CVD deaths). When using Cox regression analysis, HRs were higher in the ex-smoker and current smoker groups than in the never-smoker group, and HRs were also higher in the DM groups than in the NDM groups. When using competing risk analysis, SHRs were almost the same as the HRs of Cox regression analysis (DM and ex-smoker 6.06, DM and current smoker 10.12). Conclusions: The combination of T2DM and smoking is a strong risk factor for total cancer mortality in Japanese men.

Impact of use of angiotensin II receptor blocker on all-cause mortality in hemodialysis patients: prospective cohort study using a propensity-score analysis

Marenao Tanaka, Tomohisa Yamashita, Masayuki Koyama, Norihito Moniwa, Kohei Ohno, Kaneto Mitsumata, Takahito Itoh, Masato Furuhashi, Hirofumi Ohnishi, Hideaki Yoshida, Kazufumi Tsuchihashi, Tetsuji Miura

CLINICAL AND EXPERIMENTAL NEPHROLOGY ( SPRINGER ) 20 ( 3 ) 469 - 478 2016年06月 [査読有り]

It is controversial whether treatment with an angiotensin II receptor blocker (ARB) or a calcium channel blocker (CCB) improves prognosis of hemodialysis (HD) patients. This study was designed as a multicenter prospective cohort study. HD patients (n = 1071) were enrolled from 22 institutes in January 2009 and followed up for 3 years. Patients with missing data, kidney transplantation or retraction of consent during the follow-up period (n = 204) were excluded, and 867 patients contributed to analysis of mortality. Propensity score (PS) for use of ARB and that for CCB was calculated using a multiple logistic regression model. ARB and CCB were prescribed in 45.6 and 54.7 % of patients at enrollment. During the 3-year follow-up period, all-cause mortality and cardiovascular mortality rates were 18.8 and 5.1 %, respectively. Kaplan-Meier curves showed that all-cause and cardiovascular mortality rates were lower in the ARB group than in the non-ARB group, though the mortality rates were similar in the CCB group and non-CCB group. In PS-stratified Cox regression analysis, ARB treatment was associated with 34 and 45 % reduction of all-cause death and cardiovascular death, respectively. In PS matching analysis, ARB treatment was associated with a significant reduction (46 % reduction) in the risk of all-cause death. A significant impact of CCB treatment on all-cause or cardiovascular mortality was not detected in PS analysis. The use of an ARB, but not a CCB, is associated with reduced all-cause and cardiovascular mortalities in patients on HD.

Weight gain and alcohol drinking associations with breast cancer risk in Japanese postmenopausal women - results from the Japan collaborative cohort (JACC) study

Junichi Nitta, Masanori Nojima, Hirofumi Ohnishi, Mitsuru Mori, Kenji Wakai, Sadao Suzuki, Yoshihisa Fujino, Yingsong Lin, Koji Tamakoshi, Akiko Tamakoshi

Asian Pacific Journal of Cancer Prevention ( Asian Pacific Organization for Cancer Prevention ) 17 ( 3 ) 1437 - 1443 2016年04月 [査読有り]

Background: We investigated four factors, height, weight gain since age 20, physical activity, and alcohol drinking, for associations with risk of breast cancer (BC) according to menopausal status, using the latest data of the Japan Collaborative Cohort Study (JACC Study). Materials and Methods: We confined the analysis to 24 areas available of cancer incidence information, excluding women with a previous diagnosis of BC. Baseline data were collected from 38,610 (9,367 premenopausal, and 29,243 postmenopausal) women during 1988 and 1990. The study subjects were followed-up at the end of 2009, and 273 (84 premenopausal, and 189 postmenopausal) cases of BC were newly diagnosed in 501,907 person-years. The Cox model was used to estimate a hazards ratio (HR) and its 95% confidence interval (CI) of BC risk. Results: As a result of the multivariate analysis adjusting for age at baseline survey, age at menarche, number of live births, and, age at first delivery, weight gain since age 20 of 6.7 kg-9.9 kg, and ≥10.0 kg were significantly associated with increased risk for postmenopausal BC (HR=2.48, 95% CI 1.40-4.41, and, HR=2.94, 95% CI 1.84-4.70, respectively). Significantly increased trend of BC risk was also observed in weight gain since age 20 (p for trend, p < 0.001). Amount of ethanol intake per day≥15.0 g was significantly associated with increased risk for postmenopausal BC in the multivariable-adjusted analysis (HR=2.74, 95% CI 1.32-5.70). Conclusions: Higher weight gain in adulthood and larger amounts of ethanol intake were significantly associated with increased risk of BC in Japanese postmenopausal women. None of the investigated factors were significantly associated with BC risk in Japanese premenopausal women.

A Cross-Sectional Study on Socioeconomic Systems Supporting Outpatients With Parkinson's Disease in Japan

Aiko Matsushima, Akihisa Matsumoto, Fumio Moriwaka, Sanae Honma, Kazunori Itoh, Keiko Yamada, Shun Shimohama, Hirofumi Ohnishi, Junichi Matsushima, Mitsuru Mori

JOURNAL OF EPIDEMIOLOGY ( JAPAN EPIDEMIOLOGICAL ASSOC ) 26 ( 4 ) 185 - 190 2016年04月 [査読有り]

Objectives: We conducted a cross-sectional study to evaluate the socioeconomic systems supporting outpatients with Parkinson's disease (PD) in Japan. Methods: The study was performed in 2013 at two private hospitals and one clinic in Hokkaido Prefecture, Japan. A survey was conducted with 248 consecutive PD patients, and the data from 237 PD outpatients were analyzed after excluding 11 patients who did not meet inclusion criteria. Monthly medical and transportation payments as a PD outpatient were selected as outcome variables, and their association with various explanatory variables, such as utilization of support systems for PD outpatients, were evaluated using logistic regression model analysis. Results: After controlling for potential confounding variables, the utilization of the system providing financial aid for treatment for patients with intractable disease was significantly inversely associated with monthly medical payment among PD outpatients (OR 0.46; 95% CI, 0.22-0.95). Experience of hospital admission for PD treatment was significantly positively associated with monthly transportation payment (OR 4.74; 95% CI, 2.18-10.32). Monthly medical payment was also significantly positively associated with monthly transportation payment (OR 4.01; 95% CI, 2.23-7.51). Conclusions: Use of Japanese public financial support systems may be associated with reductions in medical payments for PD outpatients. However, those systems may not have supported transportation payments, and higher transportation payments may be associated with an increased risk of hospitalization.

Therapeutic temperature modulation in severe or moderate traumatic brain injury: a propensity score analysis of data from the Nationwide Japan Neurotrauma Data Bank

Kei Miyata, Hirofumi Ohnishi, Kunihiko Maekawa, Takeshi Mikami, Yukinori Akiyama, Satoshi Iihoshi, Masahiko Wanibuchi, Nobuhiro Mikuni, Shuji Uemura, Katsutoshi Tanno, Eichi Narimatsu, Yasufumi Asai

JOURNAL OF NEUROSURGERY ( AMER ASSOC NEUROLOGICAL SURGEONS ) 124 ( 2 ) 527 - 537 2016年02月 [査読有り]

OBJECTIVE In patients with severe traumatic brain injury (TBI), a randomized controlled trial revealed that outcomes did not significantly improve after therapeutic hypothermia (TH) or normothermia (TN). However, avoiding pyrexia, which is often associated with intracranial disorders, might improve clinical outcomes. The objective of this study was to compare neurological outcomes among patients with moderate and severe TBI after therapeutic temperature modulation (TTM) in the absence of other interventions. METHODS Data from 1091 patients were obtained from the Japan Neurotrauma Data Bank Project 2009, a cohort observational study. Patients with cardiac arrest, those with a Glasgow Coma Scale score of 3 and dilated fixed pupils, and those whose cause of death was injury to another area of the body were excluded, leaving 687 patients aged 16 years or older in this study. The patients were divided into 2 groups: the TTM group underwent TN (213 patients) or TH (82 patients), and the control group (392 patients) did not receive TTM. The primary end point for this study was the rate of poor outcome at hospital discharge, and the secondary end point was in -hospital death. Out of the 208 total items in the database, 29 variables that could potentially affect outcome were matched using the propensity score (PS) method in order to reduce selection bias and balance the baseline characteristics. RESULTS From each group, 141 patients were extracted using the PS -matching process. Among the patients in the TTM group, 29 had undergone TH and 112 had undergone TN. In a log -rank test using Kaplan -Meier survival curves, no significant differences in patient outcome or death were observed between the 2 groups (poor outcome, p = 0.83; death, p = 0.18). A Cox proportional -hazards regression analysis established the HR for poor outcome and mortality at 1.03 (95% CI 0.78-1.36, p = 0.83) and 1.34 (95% CI 0.87-2.07, p = 0.18), respectively. CONCLUSIONS There was no clear improvement in neurological outcomes after TTM in patients with moderate or severe TBI. To elucidate the role of TTM in patients with these injuries, a prospective study is needed with long-term follow-up using specific target temperatures.

Dietary sodium-to-potassium ratio as a risk factor for stroke, cardiovascular disease and all-cause mortality in Japan: the NIPPON DATA80 cohort study

Akira Okayama, Nagako Okuda, Katsuyuki Miura, Tomonori Okamura, Takehito Hayakawa, Hiroshi Akasaka, Hirofumi Ohnishi, Shigeyuki Saitoh, Yusuke Arai, Yutaka Kiyohara, Naoyuki Takashima, Katsushi Yoshita, Akira Fujiyoshi, Maryam Zaid, Takayoshi Ohkubo, Hirotsugu Ueshima

BMJ OPEN ( BMJ PUBLISHING GROUP ) 6 ( 7 ) e011632 2016年 [査読有り]

Objectives: To evaluate the impact of dietary sodium and potassium (Na-K) ratio on mortality from total and subtypes of stroke, cardiovascular disease (CVD) and all causes, using 24-year follow-up data of a representative sample of the Japanese population. Setting: Prospective cohort study. Participants: In the 1980 National Cardiovascular Survey, participants were followed for 24 years (NIPPON DATA80, National Integrated Project for Prospective Observation of Non-communicable Disease And its Trends in the Aged). Men and women aged 30-79 years without hypertensive treatment, history of stroke or acute myocardial infarction (n=8283) were divided into quintiles according to dietary Na-K ratio assessed by a 3-day weighing dietary record at baseline. Age-adjusted and multivariable-adjusted HRs were calculated using the Mantel-Haenszel method and Cox proportional hazards model. Primary outcome measures: Mortality from total and subtypes of stroke, CVD and all causes. Results: A total of 1938 deaths from all causes were observed over 176 926 person-years. Na-K ratio was significantly and non-linearly related to mortality from all stroke (p=0.002), CVD (p=0.005) and total mortality (p=0.001). For stroke subtypes, mortality from haemorrhagic stroke was positively related to Na-K ratio (p=0.024). Similar relationships were observed for men and women. The observed relationships remained significant after adjustment for other risk factors. Quadratic non-linear multivariable-adjusted HRs (95% CI) in the highest quintile versus the lowest quintile of Na-K ratio were 1.42 (1.07 to 1.90) for ischaemic stroke, 1.57 (1.05 to 2.34) for haemorrhagic stroke, 1.43 (1.17 to 1.76) for all stroke, 1.39 (1.20 to 1.61) for CVD and 1.16 (1.06 to 1.27) for all-cause mortality. Conclusions: Dietary Na-K ratio assessed by a 3-day weighing dietary record was a significant risk factor for mortality from haemorrhagic stroke, all stroke, CVD and all causes among a Japanese population.

Does a Reduction in the Glomerular Filtration Rate Increase the Overall Severity of Coronary Artery Stenosis?

Junichi Nishida, Nobuaki Kokubu, Mina Kawamukai, Akiyoshi Hashimoto, Hirofumi Ohnishi, Hidemichi Kouzu, Yoshito Ohnuma, Tohru Hasegawa, Akihito Tsuchida, Tetsuji Miura

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE ) 55 ( 8 ) 871 - 877 2016年 [査読有り]

Objective Chronic kidney disease is a risk factor of coronary events, however, its impact on coronary artery stenosis has not yet been clarified with the use of a large database. We examined the association between a reduced glomerular filtration rate (GFR) and the overall severity of coronary stenosis. Methods We enrolled 1,150 patients [mean age, 68 +/- 12 (SD) years; 66.6% men] who consecutively underwent coronary angiography for suspected stable angina pectoris. The overall severity of stenosis in the coronary arteries was assessed by the Gensini score (GS), and its logarithmic values (log-GS) were used for statistical analyses since the GS does not follow a normal distribution. Results The log-GS was significantly larger in men than in women (2.5 +/- 1.5 vs. 1.9 +/- 1.7), while the estimated GFR (eGFR) and comorbidities were comparable between both sexes. A multivariate regression analysis indicated that age, smoking, eGFR, HDL-cholesterol and HbA1c were independent explanatory variables of the log-GS in men, although the eGFR explained only 1.2% of the log-GS variation. In women, the eGFR was not included in the significant explanatory variables shown by the multivariate analysis. However, the sex difference in the regression for the eGFR-log-GS relationship was not statistically significant. Conclusion A reduced eGFR is a significant, but minor, determinant of the overall severity of coronary artery stenosis in men and potentially women.

Factors influencing attitudes toward end-of-life care by care workers at special nursing homes for the elderly: A Cross-sectional study in Japan

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

札幌医学雑誌 ( 札幌医科大学 ) 84 ( 1-6 ) 27 - 33 2015年12月

Objectives: The purpose of this study was to clarify factors influencing care workers' attitudes toward end-of-life (EOL) care characteristics at special nursing homes (SNHs). Methods: A questionnaire was initially sent to 630 care workers at 19 SNHs in October 2012. Written informed consent was obtained from 253 of these workers (40.2%), who then completed and returned the questionnaires. Participants were asked to reply to questions covering demographic data, work environment, depression status, experiences/education concerning EOL, communication skills, and attitudes toward EOL care. The Japanese version of the Frommelt Attitude Toward Care of the Dying Scale, Form B (FATCOD-B-J) assessment instrument was used in the analysis of the data received. Using the median value of the FATCOD-B-J score, 130 subjects were allocated to the high score (HS) group (FATCOD-B-J?23) and 123 to the low score (LS) group (FATCOD-B-J<23). In the LS group, the odds ratios (ORs) and their 95% confidence intervals (95% CIs) of participants exhibiting relatively negative attitudes toward EOL care were calculated and adjusted for potential confounding factors using multivariate logistic regression model analysis. Results: Length of employment in the facilities of between 5 and 9 years (OR 0.37, 95% CI 0.16-0.87) as well as over 10 years (OR 0.39, 95% CI 0.16-0.96) was significantly associated with a decreased risk of placement in the LS group. Furthermore, moderate (OR 0.44, 95% CI 0.24-0.80) as well as high (OR 0.35, 95%CI 0.17-0.75) communication skills in accepting other opinions, were significantly associated with decreased risk of placement in the LS group. Conclusions: After adjustments for potential confounding variables, results indicated that extended experience as a care worker and higher communication skills in accepting other opinions were significantly associated with a reduced risk of negative attitudes toward EOL care.

Oncological benefit of primary tumor resection with high tie lymph node dissection in unresectable colorectal cancer with synchronous peritoneal metastasis: a propensity score analysis of data from a multi-institute database

Tomohisa Furuhata, Kenji Okita, Toshihiko Nishidate, Koichi Hirata, Hirofumi Ohnishi, Hirotoshi Kobayashi, Kenjiro Kotake, Kenichi Sugihara

INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY ( SPRINGER JAPAN KK ) 20 ( 5 ) 922 - 927 2015年10月 [査読有り]

Peritoneal metastasis is recognized as a predictor of poor prognosis in patients with colorectal cancer, and whether surgical intervention for peritoneal metastasis has any clinical benefit has remained controversial. The purposes of this study were to identify prognostic factors in cases of unresectable colorectal cancer with synchronous peritoneal metastasis and to clarify the impacts of primary tumor resection with high tie lymph node dissection. A multi-institutional retrospective analysis was conducted of 579 patients who underwent resection of the primary tumor for unresectable colorectal cancer with peritoneal metastasis between 1991 and 2007. For these 579 patients, clinicopathological variables were analyzed for prognostic significance using Cox proportional hazards model and propensity score analysis to mitigate the selection bias. Multivariate analysis revealed hematogenous metastasis (p < 0.001), histology of the tumor (p = 0.006), postoperative chemotherapy (p < 0.001), and lymph node dissection (p = 0.001) as independent prognostic factors. In the propensity-matched cohort, patients treated with high tie lymph node dissection showed a significantly better overall survival than those with low tie lymph node dissection (median overall survival 13.0 vs. 11.5 months; p = 0.041). It is suggested that primary tumor resection with high tie lymph node dissection favorably affects survival, even in unresectable colorectal cancer with peritoneal metastasis.

Relationship of serum isoflavone, insulin and adiponectin levels with breast cancer risk

Machiko Minatoya, Goro Kutomi, Sumiyo Asakura, Seiko Otokozawa, Yukiko Sugiyama, Hirofumi Ohnishi, Hiroshi Akasaka, Tetsuji Miura, Mitsuru Mori, Koichi Hirata

BREAST CANCER ( SPRINGER JAPAN KK ) 22 ( 5 ) 452 - 461 2015年09月 [査読有り]

Background Obesity is one of the well-known risk factors of breast cancer. Accumulating evidence suggests that adiponectin, an obesity-related hormone, is inversely associated with breast cancer risk, particularly in postmenopausal women. Obesity is also associated with high levels of insulin. In addition, studies have suggested that the soy isoflavones present in the traditional Japanese diet have been associated with decreased risk of breast cancer. However, there is no study that has assessed associations between serum levels of isoflavones, insulin, adiponectin and the risk of breast cancer all together with menopausal status. Methods In a case-control study of 63 histologically confirmed breast cancer patients and 76 controls, serum isoflavone, insulin, and high-molecular-weight (HMW) adiponectin levels and breast cancer risk were examined for their association with breast cancer risk after adjustment for various risk factors. Results Women in the highest tertile of serum HMW adiponectin levels were associated with a statistically significant decreased risk for breast cancer compared with women in the lowest tertile [odds ratio (OR), 0.09; 95 % confidence interval (CI) 0.03-0.33]. This association was observed in postmenopausal women (OR 0.06; 95 % CI 0.01-0.28), but not in premenopausal women. The observed associations were independent of possible effects of insulin, body mass index, and known risk factors for breast cancer. Serum isoflavones and insulin levels were not associated with breast cancer risk. Conclusions This study suggests that high serum HMW adiponectin levels are significantly associated with a decreased risk for breast cancer. Our result support the hypothesis that serum adiponectin may act as a potential biomarker for breast cancer.

Subjective physical and cognitive age among community-dwelling older people aged 75 years and older: differences with chronological age and its associated factors.

Ihira H, Furuna T, Mizumoto A, Makino K, Saitoh S, Ohnishi H, Shimada H, Makizako H

Aging & mental health ( ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD ) 19 ( 8 ) 756 - 761 2015年08月 [査読有り]

Objective: The aim of this cross-sectional study was to determine the associations between self-reported subjective physical and cognitive age, and actual physical and cognitive functions among community-dwelling older people aged 75years and older. Method: The sample comprised 275 older adults aged 75-91years. Two questions were asked regarding subjective age: 'How old do you feel physically?' and 'How old do you feel cognitively?' To assess physical functions, we measured handgrip strength, knee extension strength, standing balance and walking speed. Tests of attention, executive function, processing speed and memory were performed to assess actual cognitive function. Results: Subjective physical and cognitive age was associated with performance on all of the physical and cognitive tests, respectively (p < 0.01). We also found that older adults who reported themselves as feeling older than their chronological age had a slower walking speed and lower scores for word-list memory recall than those who did not report themselves as feeling older than their actual age. Conclusion: These findings suggest that promoting a fast walking speed and good memory function may help to maintain a younger subjective physical and cognitive age in older adults aged 75years and older.

Pneumococcal vaccination reduced the risk of acute otitis media: Cohort study

Junko Hasegawa, Mitsuru Mori, Satoko Showa, Aiko Matsushima, Hirofumi Ohnishi, Takeshi Tsugawa, Yuko Yoto, Hiroyuki Tsutsumi

PEDIATRICS INTERNATIONAL ( WILEY-BLACKWELL ) 57 ( 4 ) 582 - 585 2015年08月 [査読有り]

BackgroundSeven-valent pneumococcal conjugate vaccine (PCV7) was introduced to Japan in 2009, and after that invasive pneumococcal disease has gradually decreased. There are few data, however, on the effectiveness of PCV7 against acute otitis media (AOM) in Japan. MethodsFrom 10 daycare centers in Sapporo, Japan, 614 parents participated in the survey. Each parent reported whether their child subject had received one or more doses of PCV7, and, if so, the exact dates of receiving PCV7 were verified by reviewing their maternal and child health handbooks marked by a pediatrician. AOM was diagnosed by otorhinolaryngologist or pediatrician. Cox's proportional hazard model was used for calculating the hazard ratio (HR) of AOM incidence reduced by PCV7 inoculation. ResultsInoculation of PCV7 significantly reduced the risk of AOM (crude HR, 0.63; 95%CI: 0.50-0.79). Adjusting for potentially confounding variables reduced the risk further (adjusted HR, 0.32; 95%CI: 0.23-0.44). On stratification by subject age on 30 April 2012, PCV7 was significantly associated with a reduced risk of AOM in both infants <3years old, and in children 3years. ConclusionPCV7 is effectiveness in reducing the risk of AOM both in infants <3years old, and in young children 3years in Japan.

Mapping occipital bone thickness using computed tomography for safe screw placement

Tomonori Morita, Tsuneo Takebayashi, Hiroyuki Takashima, Mitsunori Yoshimoto, Kazunori Ida, Katsumasa Tanimoto, Hirofumi Ohnishi, Hiroyoshi Fujiwara, Masateru Nagae, Toshihiko Yamashita

JOURNAL OF NEUROSURGERY-SPINE ( AMER ASSOC NEUROLOGICAL SURGEONS ) 23 ( 2 ) 254 - 258 2015年08月 [査読有り]

OBJECT Safe and effective insertion of occipital bone screws requires morphological analysis of the occipital bone, which is poorly documented in the literature. The authors of this study present morphological data for determining the area of screw placement for optimal internal fixation. METHODS The subjects of this institutional review board approved retrospective study were 105 individuals without head and neck disease who underwent CT imaging at the authors' hospital. There were 55 males and 50 females, with a mean age of 57.1 years (range 20-91 years). Measurements using CT were taken according to a matrix of 55 points following a grid with 1-cm spacing based on the external occipital protuberance (EOP). RESULTS The maximum thickness of the occipital bone was at the level of the EOP at 16.4 mm. Areas with thicknesses > 8 mm were more frequent at the EOP and up to 2 cm in all directions, as well as up to 1 cm in all directions at a height of 1 cm inferiorly, and up to 3 cm from the EOP inferiorly. The male group tended to have a thicker occipital bone than the female group, and the differences were significant around the EOP. The ratio of the trabecular bone to the occipital bone thickness was > 30% in the central region. At positions more than 2 cm laterally, the ratio was < 15%, and the ratio gradually decreased further laterally. CONCLUSIONS Screws that are 8 mm long can be placed in the area extending 2 cm laterally from the EOP at the level of the superior nuchal line and approximately 3 cm inferior to the center. These results suggest that it may be possible to effectively insert a screw over a wider area than the conventional reference range.

The combination of abdominal obesity and high-sensitivity C-reactive protein predicts new-onset hypertension in the general Japanese population: the Tanno-Sobetsu study

Mizue Fujii, Hirofumi Ohnishi, Shigeyuki Saitoh, Hiroshi Akasaka, Tetsuji Miura, Mitsuru Mori

HYPERTENSION RESEARCH ( NATURE PUBLISHING GROUP ) 38 ( 6 ) 426 - 432 2015年06月 [査読有り]

The aim of this study was to examine whether the combination of abdominal obesity and high serum levels of high-sensitivity C-reactive protein (hsCRP) improves the prediction of new-onset hypertension in the general Japanese population. Participants in the Tanno-Sobetsu study, a prospective cohort study, were enrolled. Of 1516 subjects aged 30 years or older in 2002, those with hypertension or abnormal hsCRP levels were excluded, and the remaining 705 subjects were included in the present analyses. Abdominal obesity (AO) and high hsCRP levels were defined by the Japanese criteria of waist circumference and median hsCRP values, respectively. Subjects were followed up on for a maximum of 4.5 years, and the hazard ratio (HR) for new-onset hypertension was calculated using the Cox proportional hazard model. The HR for new-onset hypertension after adjustment for age, sex, fasting plasma glucose, alcohol intake, smoking, treatment for dyslipidemia and high normal blood pressure at baseline was significantly higher in the group with AO and high hsCRP (HR = 1.44, 95% CI: 1.00-2.07) compared with the reference group, a group with no AO and low hsCRP; AO alone or high hsCRP alone was not associated with a significant increase in the HR. Similar trends for the increase in the HR by AO and high hsCRP were observed in separate analyses of men and women, although the differences did not reach statistical significance. Co-presence of AO and a high level of hsCRP is associated with a high risk for new-onset hypertension in the general population.

Physical activity changes in the winter in older persons living in northern Japan: a prospective study

Atsushi Mizumoto, Hikaru Ihira, Keitaro Makino, Shigeyuki Saitoh, Hirofumi Ohnishi, Taketo Furuna

BMC GERIATRICS ( BIOMED CENTRAL LTD ) 15 43 2015年04月 [査読有り]

Background: Physical activity affects physical and mental health, prevents disease, and improves quality of life. However, physical activity also decreases with age in older persons, and is affected by adverse climatic periods. This study examined changes in physical activity during the winter season in older persons (>= 75 years of age) who were living in northern Japan, and evaluated the factors that were associated with this decline. Methods: A total of 201 older persons (83 men and 118 women; mean age, 79.7 +/- 3.8 years) participated in two separate tests that were conducted in November 2012 and February 2013. Physical activity was monitored using the Kenz Lifecorder, and mean step counts and moderate-vigorous physical activity (MVPA) times were calculated over a 1-week period. We also measured body mass index, handgrip strength, normal walking speed, functional capacity, exercise habits, snow-shovelling habits, a change in frequency (between early winter and midwinter) of outdoor excursions, the length of outdoor excursions, social support, and morbidity. Results: In the group that maintained their frequency of outdoor excursions, step counts significantly increased during midwinter compared with early winter (p < 0.01). In the group with a lower frequency of outdoor excursions, MVPA was significantly decreased during midwinter compared with early winter (p < 0.05). After adjusting for other variables, logistic regression analysis showed that weakness (odds ratio [OR]: 2.89, p < 0.05) was independently associated with a decline in step counts. Age (OR: 1.12, p < 0.05) and a change in frequency of outdoor excursions (OR: 0.75, p < 0.01) were independently associated with a decline in MVPA. Conclusions: Older persons should be supported in their attempts to go outdoors during midwinter. They should be provided with intervention programs to increase their physical activity at home.

Estimated Daily Intake and Seasonal Food Sources of Quercetin in Japan

Haruno Nishimuro, Hirofumi Ohnishi, Midori Sato, Mayumi Ohnishi-Kameyama, Izumi Matsunaga, Shigehiro Naito, Katsunari Ippoushi, Hideaki Oike, Tadahiro Nagata, Hiroshi Akasaka, Shigeyuki Saitoh, Kazuaki Shimamoto, Masuko Kobori

NUTRIENTS ( MDPI AG ) 7 ( 4 ) 2345 - 2358 2015年04月 [査読有り]

Quercetin is a promising food component, which can prevent lifestyle related diseases. To understand the dietary intake of quercetin in the subjects of a population-based cohort study and in the Japanese population, we first determined the quercetin content in foods available in the market during June and July in or near a town in Hokkaido, Japan. Red leaf lettuce, asparagus, and onions contained high amounts of quercetin derivatives. We then estimated the daily quercetin intake by 570 residents aged 20-92 years old in the town using a food frequency questionnaire (FFQ). The average and median quercetin intakes were 16.2 and 15.5 mg day(-1), respectively. The quercetin intakes by men were lower than those by women; the quercetin intakes showed a low correlation with age in both men and women. The estimated quercetin intake was similar during summer and winter. Quercetin was mainly ingested from onions and green tea, both in summer and in winter. Vegetables, such as asparagus, green pepper, tomatoes, and red leaf lettuce, were good sources of quercetin in summer. Our results will help to elucidate the association between quercetin intake and risks of lifestyle-related diseases by further prospective cohort study and establish healthy dietary requirements with the consumption of more physiologically useful components from foods.

FABP4 is Secreted from Adipocytes by Adenyl Cyclase-PKA- and Guanylyl Cyclase-PKG-Dependent Lipolytic Mechanisms

Tomohiro Mita, Masato Furuhashi, Shinya Hiramitsu, Junnichi Ishii, Kyoko Hoshina, Shutaro Ishimura, Takahiro Fuseya, Yuki Watanabe, Marenao Tanaka, Kohei Ohno, Hiroshi Akasaka, Hirofumi Ohnishi, Hideaki Yoshida, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

OBESITY ( WILEY-BLACKWELL ) 23 ( 2 ) 359 - 367 2015年02月 [査読有り]

ObjectiveFatty acid-binding protein 4 (FABP4) is expressed in adipocytes, and elevated plasma FABP4 level is associated with obesity-mediated metabolic phenotype. Postprandial regulation and secretory signaling of FABP4 has been investigated. MethodsTime courses of FABP4 levels were examined during an oral glucose tolerance test (OGTT; n=53) or a high-fat test meal eating (n=35). Effects of activators and inhibitors of adenyl cyclase (AC)-protein kinase A (PKA) signaling and guanylyl cyclase (GC)-protein kinase G (PKG) signaling on FABP4 secretion from mouse 3T3-L1 adipocytes were investigated. ResultsFABP4 level significantly declined after the OGTT or a high-fat meal eating, while insulin level was increased. Treatment with low and high glucose concentration or palmitate for 2 h did not affect FABP4 secretion from 3T3-L1 adipocytes. FABP4 secretion was increased by stimulation of lipolysis using isoproterenol, a (3)-adrenoceptor agonist (CL316243), forskolin, dibutyryl-cAMP and atrial natriuretic peptide, and the induced FABP4 secretion was suppressed by insulin or an inhibitor of PKA (H-89), PKG (KT5823) or hormone sensitive lipase (CAY10499). ConclusionsFABP4 is secreted from adipocytes in association with lipolysis regulated by AC-PKA- and GC-PKG-mediated signal pathways. Plasma FABP4 level declines postprandially, and suppression of FABP4 secretion by insulin-induced anti-lipolytic signaling may be involved in this decline in FABP4 level.

IQ is an independent predictor of glycated haemoglobin level in young and middle-aged adults with intellectual disability

T. Yano, T. Miki, T. Itoh, H. Ohnishi, M. Asari, S. Chihiro, A. Yamamoto, K. Aotsuka, N. Kawakami, J. Ichikawa, Y. Hirota, T. Miura

Diabetic Medicine ( Blackwell Publishing Ltd ) 32 ( 1 ) 129 - 132 2015年01月 [査読有り]

Aims: Here we examined whether intellectual disability is independently associated with hyperglycaemia. Methods: We recruited 233 consecutive young and middle-aged adults with intellectual disability. After exclusion of subjects on medication for metabolic diseases or with severe intellectual disability (IQ < 35), 121 subjects were divided by IQ into a group with moderate intellectual disability (35≤IQ≤50), a mild intellectual disability group (51≤IQ≤70) and a borderline group (IQ > 70). Results: HbA1c level was higher in subjects with moderate intellectual disability (42 ± 9 mmol/mol 6.0 ± 0.8%) than those in the borderline group (36 ± 4 mmol/mol 5.5 ± 0.3%) and mild intellectual disability group (37 ± 5 mmol/mol 5.5 ± 0.5%) groups. HbA1c level was correlated with age, BMI, blood pressure, serum triglycerides and IQ in simple linear regression analysis. Multiple regression analysis indicated that IQ, age, BMI and diastolic blood pressure were independent explanatory factors of HbA1c level. Conclusions: An unfavourable effect of intellectual disability on lifestyle and untoward effect of hyperglycaemia on cognitive function may underlie the association of low IQ with hyperglycaemia.

Urinary Angiotensin-Converting Enzyme 2 in Hypertensive Patients May Be Increased by Olmesartan, an Angiotensin II Receptor Blocker

Masato Furuhashi, Norihito Moniwa, Tomohiro Mita, Takahiro Fuseya, Shutaro Ishimura, Kohei Ohno, Satoru Shibata, Marenao Tanaka, Yuki Watanabe, Hiroshi Akasaka, Hirofumi Ohnishi, Hideaki Yoshida, Hideki Takizawa, Shigeyuki Saitoh, Nobuyuki Ura, Kazuaki Shimamoto, Tetsuji Miura

AMERICAN JOURNAL OF HYPERTENSION ( OXFORD UNIV PRESS ) 28 ( 1 ) 15 - 21 2015年01月 [査読有り]

BACKGROUND Angiotensin-converting enzyme 2 (ACE2) is highly expressed in the kidney and converts angiotensin (Ang) II to Ang-(1-7), a renoprotective peptide. Urinary ACE2 has been shown to be elevated in patients with chronic kidney disease. However, the effects of antihypertensive agents on urinary ACE2 remain unclear. METHODS Of participants in the Tanno-Sobetsu cohort study in 2011 (n = 617), subjects on no medication (n = 101) and hypertensive patients treated with antihypertensive agents, including the calcium channel blockers amlodipine and long-acting nifedipine; the ACE inhibitor enalapril; and the Ang II receptor blockers losartan, candesartan, valsartan, telmisartan, and olmesartan, for more than 1 year (n = 100) were enrolled, and urinary ACE2 level was measured. RESULTS Glucose and hemoglobin A1c were significantly higher in patients treated with enalapril, telmisartan or olmesartan than in the control subjects. Urinary albumin-to-creatinine ratio (UACR) was significantly higher in patients treated with enalapril than in the control subjects. Urinary ACE2 level was higher in the olmesartan-treated group, but not the other treatment groups, than in the control group. Urinary ACE2 level was positively correlated with systolic blood pressure (r = 0.211; P = 0.003), UACR (r = 0.367; P < 0.001), and estimated salt intake (r = 0.260; P < 0.001). Multivariable regression analysis after adjustment of age, sex, and the correlated indices showed that the use of olmesartan was an independent predictor of urinary ACE2 level. CONCLUSIONS In contrast with other antihypertensive drugs, olmesartan may uniquely increase urinary ACE2 level, which could potentially offer additional renoprotective effects.

Physical Activity during Winter in Old-Old Women Associated with Physical Performance after One Year: A Prospective Study.

Atsushi Mizumoto, Hikaru Ihira, Keitaro Makino, Shigeyuki Saitoh, Hirofumi Ohnishi, Taketo Furuna

Current gerontology and geriatrics research 2015 253451 - 253451 2015年 [査読有り] [国際誌]

Background. The aim of this study was to evaluate whether the decline of physical activity during winter influences physical performances (after 1 year) in old-old women. Methods. Fifty-three Japanese women (mean age: 78.4 ± 3.2 years) participated in this study. Data of physical activity was collected by using an accelerometer at baseline and 3-month follow-up, and participants who decreased step counts in this period were defined as declining groups. We measured grip strength, knee extensor strength, total length of the center of gravity, hip walking distance, and maximum walking speed to evaluate physical performances at baseline and 1-year follow-up. Repeated-measures analysis of variance determined the difference in physical performance between declining groups and maintenance group with maintained or improved step counts. Results. Daily step counts for 22 older women (41.5%) decreased during winter. A statistically significant interaction effect between group and time was found for maximum walking speed (F(1,50) = 5.23, p = 0.03). Post hoc comparisons revealed that walking speed in the maintenance group significantly increased compared with baseline (p = 0.01); the declining group showed no significant change (p = 0.44). Conclusion. Change of physical activity during winter influences the physical performance level after 1 year in community-dwelling old-old women, particularly its effect on maximum walking speed.

Associations of serum isoflavone, adiponectin and insulin levels with risk for epithelial ovarian cancer: Results of a case-control study

Seiko Otokozawa, Ryoichi Tanaka, Hiroshi Akasaka, Eiki Ito, Sumiyo Asakura, Hirofumi Ohnishi, Shigeyuki Saito, Tetsuji Miura, Tsuyoshi Saito, Mitsuru Mori

Asian Pacific Journal of Cancer Prevention ( Asian Pacific Organization for Cancer Prevention ) 16 ( 12 ) 4987 - 4991 2015年 [査読有り]

Background: The aim of this study was to examine the association of serum isoflavones, adiponectin, and insulin levels with ovarian cancer risk. Materials and Methods: We gathered cases with histologically confirmed epithelial ovarian cancer at Sapporo Medical University Hospital from October 2010 to September 2012. Potential controls were recruited from female inpatients without any history of cancer or diabetes mellitus in different wards of the same hospital over the same period of time. Serum isoflavones, adiponectin, and insulin levels were measured in order to estimate associations with ovarian cancer risk in a case-control study. Data from 71 cases and 80 controls were analyzed with a logistic regression model adjusting for known risk factors. Results: A significant reduction in ovarian cancer risk was observed for the high tertile of serum daidzein level versus the low (P< inf> trend< /inf> < 0.001). A significant reduction in ovarian cancer risk was also observed for the high tertile of serum glycitein level versus the low (P< inf> trend< /inf> =0.005). Furthermore, a significant reduction in ovarian cancer risk was observed for the high tertile of serum adiponectin level versus the low (P< inf> trend< /inf> =0.004). Conversely, serum insulin level showed significantly elevated risk for ovarian cancer with the high tertile versus the low P< inf> trend< /inf> < 0.001). Conclusions: Decreased serum isoflavones levels, such as those for daidzein and glycitein, decreased serum adiponectin levels, and increased serum insulin levels could be shown to be associated with elevated risk of ovarian cancer.

Pericardial Effusion and Multiple Organ Involvement Are Independent Predictors of Mortality in Patients with Systemic Light Chain Amyloidosis

Satoshi Yuda, Toshiaki Hayashi, Kenji Yasui, Atsuko Muranaka, Hirofumi Ohnishi, Akiyoshi Hashimoto, Tadao Ishida, Kazufumi Tsuchihashi, Yasuhisa Shinomura, Naoki Watanabe, Tetsuji Miura

INTERNAL MEDICINE ( JAPAN SOC INTERNAL MEDICINE ) 54 ( 15 ) 1833 - 1840 2015年 [査読有り]

Objective Left ventricular (LV) functions assessed by echocardiography and cardiac biomarkers are strong predictors of mortality in patients with systemic light chain (AL) amyloidosis. However, most previous studies have been conducted in Western countries, and the predictors of mortality in Asian patients with AL amyloidosis have not been characterized. To address this issue, we aimed to determine the predictors of mortality in Asian patients with biopsy-confirmed AL amyloidosis. Methods We retrospectively enrolled 31 patients (59 +/- 11 years, 55% men) in whom AL amyloidosis was confirmed by biopsies from cardiac or non-cardiac tissues. Of these patients, 15 (48%) met the international echocardiographic criteria for cardiac amyloidosis (mean LV wall thickness > 12 mm without other causes of LV hypertrophy). Results During a mean follow-up period of 21 +/- 20 months, 15 patients died. Non-survivors had a higher number of involved organs, lower e', and higher rates of E/e' > 15, pericardial effusion (PE), low voltage on an electrocardiogram and a New York Heart Association (NYHA) functional class >= III, compared with survivors. In multivariate analysis, a NYHA functional class >= III (p=0.024) and cardiac involvement (p=0.032) were independent predictors of PE in patients with AL amyloidosis. Multivariate Cox proportional hazard analysis indicated that PE (hazard ratio: 21.9, p=0.025) and the number of involved organs (hazard ratio: 2.8, p=0.015), but not LV diastolic parameters of tissue Doppler echocardiography, independently predict mortality in patients with AL amyloidosis. Conclusion PE and multiple organ involvement, compared with e' and E/e', are stronger predictors of mortality in patients with AL amyloidosis. The advanced disease stage of AL amyloidosis might underlie the strong association between PE and a poor outcome.

Urinary Excretion of Fatty Acid-Binding Protein 4 is Associated with Albuminuria and Renal Dysfunction

Yusuke Okazaki, Masato Furuhashi, Marenao Tanaka, Tomohiro Mita, Takahiro Fuseya, Shutaro Ishimura, Yuki Watanabe, Kyoko Hoshina, Hiroshi Akasaka, Hirofumi Ohnishi, Hideaki Yoshida, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

PLOS ONE ( PUBLIC LIBRARY SCIENCE ) 9 ( 12 ) e115429 2014年12月 [査読有り]

Background: Fatty acid-binding protein 4 (FABP4/A-FABP/aP2) is expressed in not only adipocytes and macrophages but also peritubular capillaries in the normal kidney. We recently demonstrated that ectopic expression of FABP4, but not FABP1 known as liver FABP (L-FABP), in the glomerulus is associated with progression of proteinuria and renal dysfunction. However, urinary excretion of FABP4 has not been investigated. Methods: Subjects who participated in the Tanno-Sobetsu Study, a study with a population-based cohort design, in 2011 (n=392, male/female: 166/226) were enrolled. Urinary FABP4 (U-FABP4) and urinary albumin-to-creatinine ratio (UACR) were measured. Change in estimated glomerular filtration rate (eGFR) was followed up one year later. Results: In 93 (23.7%) of the 392 subjects, U-FABP4 level was below the sensitivity of the assay. Subjects with undetectable U-FABP4 were younger and had lower UACR and higher eGFR levels than subjects with measurable U-FABP4. U-FABP4 level was positively correlated with age, systolic blood pressure and levels of serum FABP4 (S-FABP4), triglycerides, hemoglobin A1c (HbA1c), urinary FABP1 (U-FABP1) and UACR (r=0.360, p<0.001). Age, S-FABP4, U-FABP1 and UACR were independent predictors of U-FABP4. On the other hand, systolic blood pressure, HbA1c and U-FABP4 were independently correlated with UACR. Reduction in eGFR after one year was significantly larger in a group with the highest tertile of baseline U-FABP4 than a group with the lowest tertile. Conclusions: Urinary FABP4 level is independently correlated with level of albuminuria and possibly predicts yearly decline of eGFR. U-FABP4 would be a novel biomarker of glomerular damage.

Elevation of circulating fatty acid-binding protein 4 is independently associated with left ventricular diastolic dysfunction in a general population

Takahiro Fuseya, Masato Furuhashi, Satoshi Yuda, Atsuko Muranaka, Mina Kawamukai, Tomohiro Mita, Shutaro Ishimura, Yuki Watanabe, Kyoko Hoshina, Marenao Tanaka, Kohei Ohno, Hiroshi Akasaka, Hirofumi Ohnishi, Hideaki Yoshida, Shigeyuki Saitoh, Kazuaki Shimamoto, Tetsuji Miura

CARDIOVASCULAR DIABETOLOGY ( BIOMED CENTRAL LTD ) 13 126 2014年08月 [査読有り]

Background: Fatty acid-binding protein 4 (FABP4) is expressed in both adipocytes and macrophages. Recent studies have shown secretion of FABP4 from adipocytes and association of elevated serum FABP4 level with obesity, insulin resistance, hypertension, and atherosclerosis. However, little is known about role of FABP4 in cardiac function. Methods: From the database of the Tanno-Sobetsu Study, data for 190 subjects (male/female: 82/108) who were not treated with any medication and underwent echocardiography in 2011 or 2012 were retrieved for analyses of relationships between serum FABP4 concentration, metabolic markers and parameters of echocardiography. Results: Serum FABP4 level was positively correlated with age, body mass index (BMI), blood pressure (BP), LDL cholesterol, HOMA-R and mean left ventricular (LV) wall thickness (LVWT, males: r = 0.315, females: r = 0.401, p < 0.01) and was negatively correlated with HDL cholesterol, estimated glomerular filtration rate (eGFR) and peak myocardial velocity during early diastole (e'; males: r = -0.434, females: r = -0.353, p < 0.01), an index of LV diastolic function. However, no significant correlation was found between FABP4 level and LV end-diastolic dimension, LV ejection fraction or LV mass index. There were significant correlations of e' with age, BMI, BP, eGFR, brain natriuretic peptide (BNP), FABP4, metabolic markers and LVWT. Multivariate regression analysis adjusted by HOMA-R, BMI, eGFR, BNP or LVWT in addition to age, gender and BP revealed that serum FABP4 concentration was independently correlated with e'. Conclusions: Elevation of circulating FABP4 may contribute to LV diastolic dysfunction in a general population.

Effectiveness of influenza vaccine in children in day-care centers of Sapporo

Mitsuru Mori, Junko Hasegawa, Satoko Showa, Aiko Matsushima, Hirofumi Ohnishi, Yuko Yoto, Hiroyuki Tsutsumi

PEDIATRICS INTERNATIONAL ( WILEY-BLACKWELL ) 56 ( 1 ) 53 - 56 2014年02月 [査読有り]

Counts of Slackia sp strain NATTS in Intestinal Flora are Correlated to Serum Concentrations of Equol both in Prostate Cancer Cases and Controls in Japanese Men

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

ASIAN PACIFIC JOURNAL OF CANCER PREVENTION ( ASIAN PACIFIC ORGANIZATION CANCER PREVENTION ) 15 ( 6 ) 2693 - 2697 2014年 [査読有り]

Background: Isoflavones, which are included in soybeans, have been suggested to protect against prostate cancer. Equol, one of isoflavones, is an intestinally derived bacterial metabolite of daidzein. A newly identified equol-producing bacterium, Slackia sp. strain NATTS, with a high equol-producing activity was isolated from human feces in Japanese adults. Counts of Slackia sp. strain NATTS in intestinal flora have not been assessed with regard to prostate cancer risk. In this study, we investigated the association of serum isoflavones and counts of Slackia sp. strain NATTS with prostate cancer risk in a case-control study. Materials and Methods: Concentrations of isoflavones and counts of Slackia sp. strain NATTS in feces were measured from 44 patients with prostate cancer and 28 hospital controls. The risk of prostate cancer was evaluated in terms of odds ratios (ORs) and 95% confidence intervals (CIs) by the logistic regression analysis. Results: The detection proportions of Slackia sp. strain NATTS in cases and controls were 34.1% and 25.0%, respectively. Counts of Slackia sp. strain NATTS were significantly correlated with serum concentrations of equol both in cases and controls (Spearman correlation coefficients, r(s)=0.639 and r(s)=0.572, p<0.01, respectively). Serum concentrations of genistein, daidzein, glycitein, and equol were not significantly associated with risk of prostate cancer. Conclusions: This study found that counts of Slackia sp. strain NATTS correlated with serum concentrations of equol both in prostate cancer cases and controls, but serum isoflavone concentrations were not associated with risk of prostate cancer in our patients.

Relation of Serum Adiponectin Levels and Obesity with Breast Cancer: A Japanese Case-Control Study

Machiko Minatoya, Goro Kutomi, Hiroaki Shima, Sumiyo Asakura, Seiko Otokozawa, Hirofumi Ohnishi, Hiroshi Akasaka, Tetsuji Miura, Mitsuru Mori, Koichi Hirata

ASIAN PACIFIC JOURNAL OF CANCER PREVENTION ( ASIAN PACIFIC ORGANIZATION CANCER PREVENTION ) 15 ( 19 ) 8325 - 8330 2014年 [査読有り]

Background: It is known that obesity is one of the risk factors for breast cancer although the association may differ between ethnic groups and with the menopausal status. Recently obesity-related risk factors including serum adiponectin and insulin levels have been analyzed together with BMI in association with breast cancer risk. Materials and Methods: We measured serum high molecular weight (HMW) adiponectin and insulin levels in a hospital based case-control study, including 66 sets of Japanese female breast cancer cases and age and menopausal status matched controls. Serum levels of HMW adiponectin, insulin levels and body mass index (BMI) were examined in association with breast cancer risk with adjustment for the various known risk factors by menopausal status. Results: Women in the highest HMW adiponectin levels showed significant reduced risk of breast cancer in both pre and postmenopausal women (odds ratio (OR), 0.01; 95% confidence interval (CI), 0.00-0.26 and 0.13; 0.03-0.57, respectively). Lower BMI showed decreased breast cancer risk in both pre and postmenopausal women (OR, 0.04; 95% CI, 0.00-0.69, OR, 0.28; 95% CI, 0.07-1.11, respectively). Conclusions: These results indicated that higher serum HMW adiponectin levels and lower BMI are associated with a decreased breast cancer risk in both pre and postmenopausal women in Japan, adding evidence for the obesity link.

Physical Functions, Health-Related Outcomes, Nutritional Status, and Blood Markers in Community-Dwelling Cancer Survivors Aged 75 Years and Older

Hikaru Ihira, Atsushi Mizumoto, Keitarou Makino, Keisuke Yasuda, Yoko Miyabe, Shigeyuki Saitoh, Hirofumi Ohnishi, Taketo Furuna

ASIAN PACIFIC JOURNAL OF CANCER PREVENTION ( ASIAN PACIFIC ORGANIZATION CANCER PREVENTION ) 15 ( 7 ) 3305 - 3310 2014年 [査読有り]

Background: A cancer survivor is defined as anyone who has been diagnosed with cancer, from the time of diagnosis through the rest of their life. The purpose of this study was to examine whether physical functions, health-related outcomes, nutritional status and blood markers in community-dwelling cancer survivors aged 75 years and older are different from those who do not have cancer Materials and Methods: Two hundred seventy-five participants were asked by physicians, nurses, and physical therapists, questions regarding cancer history in a face-to-face interview. Data were collected for demographic information, physical functions, such as handgrip strength, knee extension power, abdominal muscle strength, static standing balance, walking speed and the timed-up-and-go test, health-related outcomes, nutritional status, and blood markers. The measured parameters of survivor diagnosed with cancer were compared with those without a history of cancer. Results: Thirty-seven older adults were previously diagnosed with cancer. Female cancer survivors had lower knee extension power (p<0.05), abdominal muscle strength (p<0.05), walking speed (p<0.05), timed-up-and-go test score (p<0.05), and time to spend on walking per day (p<0.05) than older women without a history of cancer. In men, none of the measured parameters were significantly different between cancer survivors and older men with no history of cancer. Conclusions: The present study shows that partial physical function of women cancer survivors aged 75 years and older differs from that in women with no history of cancer.

Circulating Levels of Fatty Acid-Binding Protein Family and Metabolic Phenotype in the General Population

Shutaro Ishimura, Masato Furuhashi, Yuki Watanabe, Kyoko Hoshina, Takahiro Fuseya, Tomohiro Mita, Yusuke Okazaki, Masayuki Koyama, Marenao Tanaka, Hiroshi Akasaka, Hirofumi Ohnishi, Hideaki Yoshida, Shigeyuki Saitoh, Tetsuji Miura

PLOS ONE ( PUBLIC LIBRARY SCIENCE ) 8 ( 11 ) e81318 2013年11月 [査読有り]

Objective: Fatty acid-binding proteins (FABPs) are a family of 14-15-kDa proteins, and some FABPs have been to be used as biomarkers of tissue injury by leak from cells. However, recent studies have shown that FABPs can be secreted from cells into circulation. Here we examined determinants and roles of circulating FABPs in a general population. Methods: From the database of the Tanno-Sobetsu Study, a study with a population-based cohort design, data in 2011 for 296 subjects on no medication were retrieved, and FABP1 similar to 5 in their serum samples were assayed. Results: Level of FABP4, but not the other isoforms, showed a gender difference, being higher in females than in males. Levels of all FABPs were negatively correlated with estimated glomerular filtration rate (eGFR), but a distinct pattern of correlation with other clinical parameters was observed for each FABP isoform; significant correlates were alanine aminotransferase (ALT), blood pressure (BP), and brain natriuretic peptide (BNP) for FABP1, none besides eGFR for FABP2, age, BP, and BNP for FABP3, age, waist circumference (WC), BP, BNP, lipid variables, high-sensitivity C-reactive protein (hsCRP), and HOMA-R for FABP4, and age, WC, BP, ALT, BNP, and HOMA-R for FABP5. FABP4 is the most strongly related to metabolic markers among FABPs. In a multivariate regression analysis, FABP4 level was an independent predictor of HOMAR after adjustment of age, gender, WC, BP, HDL cholesterol, and hsCRP. Conclusions: Each FABP isoform level showed a distinct pattern of correlation with clinical parameters, although levels of all FABPs were negatively determined by renal function. Circulating FABP4 appears to be a useful biomarker for detecting preclinical stage of metabolic syndrome, especially insulin resistance, in the general population.

HbA(1c) and the Risks for All-Cause and Cardiovascular Mortality in the General Japanese Population NIPPON DATA90

Masaru Sakurai, Shigeyuki Saitoh, Katsuyuki Miura, Hideaki Nakagawa, Hirofumi Ohnishi, Hiroshi Akasaka, Aya Kadota, Yoshikuni Kita, Takehito Hayakawa, Takayoshi Ohkubo, Akira Okayama, Tomonori Okamura, Hirotsugu Ueshima

DIABETES CARE ( AMER DIABETES ASSOC ) 36 ( 11 ) 3759 - 3765 2013年11月 [査読有り]

OBJECTIVEAssociations between HbA(1c) and cardiovascular diseases (CVD) have been reported mainly in Western countries. It is not clear whether HbA(1c) measurements are useful for assessing CVD mortality risk in East Asian populations.RESEARCH DESIGN AND METHODSThe risk for cardiovascular death was evaluated in a large cohort of participants selected randomly from the overall Japanese population. A total of 7,120 participants (2,962 men and 4,158 women; mean age 52.3 years) free of previous CVD were followed for 15 years. Adjusted hazard ratios (HRs) and 95% CIs among categories of HbA(1c) (<5.0%, 5.0-5.4%, 5.5-5.9%, 6.0-6.4%, and 6.5%) for participants without treatment for diabetes and HRs for participants with diabetes were calculated using a Cox proportional hazards model.RESULTSDuring the study, there were 1,104 deaths, including 304 from CVD, 61 from coronary heart disease, and 127 from stroke (78 from cerebral infarction, 25 from cerebral hemorrhage, and 24 from unclassified stroke). Relations to HbA(1c) with all-cause mortality and CVD death were graded and continuous, and multivariate-adjusted HRs for CVD death in participants with HbA(1c) 6.0-6.4% and 6.5% were 2.18 (95% CI 1.22-3.87) and 2.75 (1.43-5.28), respectively, compared with participants with HbA(1c) <5.0%. Similar associations were observed between HbA(1c) and death from coronary heart disease and death from cerebral infarction.CONCLUSIONSHigh HbA(1c) levels were associated with increased risk for all-cause mortality and death from CVD, coronary heart disease, and cerebral infarction in general East Asian populations, as in Western populations.

Glucagon-Like Peptide-1 Secretory Function as an Independent Determinant of Blood Pressure: Analysis in the Tanno-Sobetsu Study

Mayumi Yoshihara, Hiroshi Akasaka, Hirofumi Ohnishi, Takayuki Miki, Tetsuaki Furukawa, Satoshi Yuda, Shigeyuki Saitoh, Tetsuji Miura

PLOS ONE ( PUBLIC LIBRARY SCIENCE ) 8 ( 7 ) e67578 2013年07月 [査読有り]

Aims: Roles of glucagon-like peptide-1 (GLP-1) in extra-pancreatic tissues remain unclear. The aim of this study was to examine determinants of GLP-1 secretory function and possible contribution of GLP-1 to blood pressure (BP) regulation. Methods and Results: We recruited 128 subjects who received annual examinations and 75g-oral glucose tolerance tests (OGTT) in the Tanno-Sobetsu cohort. Subjects on regular medications for cardiovascular and/or metabolic diseases were excluded, and data for the remaining 103 subjects were used for the univariate and multivariate analyses. Age, plasma glucose (PG), hemoglobin A1c (HbA1c), plasma insulin, and serum lipids were not selected as independent determinants of fasting GLP-1 level by multiple linear regression analysis. However, age and female sex were selected as independent positive determinants of the area under the curve of GLP-1 level during OGTT (AUC(GLP-1)), an index of GLP-1 secretory function. Multiple linear regression analysis indicated that AUC(GLP-1) was an independent negative predictor of systolic BP (SBP), while AUC(GLP-1) was not correlated with fasting PG or HbA1c level. In subgroup analyses using the median of AUC(GLP-1) to divide the study subjects into high and low GLP-1 response groups, AUC(GLP-1) was significantly correlated with both SBP and diastolic BP (r = 0.40 and 0.28, respectively) in the low GLP-1 response group but not in the high GLP-1 response group. Conclusions: The results of the present study suggest that GLP-1 secretory function is involved in prevention of BP elevation and that the GLP-1 response to oral glucose rather increases with aging perhaps as an adaptive phenomenon.

無症状の日本人被験者において改変JASリスク層化は頸動脈プラークを予測するか(Does Revised JAS Risk Stratification Predict Carotid Plaque in Asymptomatic Japanese?)

Kawamukai Mina, Yuda Satoshi, Fujito Takefumi, Nishida Junichi, Mochizuki Atsushi, Kouzu Hidemichi, Muranaka Atsuko, Akasaka Hiroshi, Kokubu Nobuaki, Shimoshige Shinya, Ohnishi Hirofumi, Hashimoto Akiyoshi, Saitoh Shigeyuki, Tsuchihashi Kazufumi, Watanabe Naoki, Miura Tetsuji

Circulation Journal ( (一社)日本循環器学会 ) 77 ( Suppl.I ) 97 - 98 2013年03月

Associations between serum 25-hydroxyvitamin D concentration and physical performance in old-old people living in a northern area of Japan

Mizumoto A, Ihira H, Yasuda K, Makino K, Miyabe Y, Saitoh S, Ohnishi H, Suzuki T, Furuna T

Journal of Gerontology & Geriatric Research 2 ( 4 ) 135 2013年 [査読有り]

Consumption of dairy products and death from cardiovascular disease in the Japanese general population: the NIPPON DATA80.

Imako Kondo, Toshiyuki Ojima, Mieko Nakamura, Shinya Hayasaka, Atsushi Hozawa, Shigeyuki Saitoh, Hirofumi Ohnishi, Hiroshi Akasaka, Takehito Hayakawa, Yoshitaka Murakami, Nagako Okuda, Katsuyuki Miura, Akira Okayama, Hirotsugu Ueshima

Journal of epidemiology ( 1 ) 23 ( 1 ) 47 - 54 2013年 [査読有り] [国内誌]

BACKGROUND: Recent Western studies show an inverse association between milk and dairy product intake and cardiovascular disease (CVD). We studied the association between consumption of milk and dairy products and CVD death in Japan. METHODS: Men and women aged 30 years or older were followed for 24 years. All had participated in a national nutrition survey in 300 health districts throughout Japan in 1980. The Cox proportional hazards model was used to assess mortality risk according to tertiles of milk and dairy product intake, with the high consumption group as reference. Hazard ratios (HRs) per 100-g/day increase in consumption were also estimated. RESULTS: During the 24-year follow-up period, there were 893 CVD deaths, 174 deaths from coronary heart disease (CHD), and 417 stroke deaths among 9243 participants. For women, the HRs for death from CVD, CHD, and stroke in the low consumption group were 1.27 (95% CI: 0.99-1.58; P for trend = 0.045), 1.67 (0.99-2.80; P = 0.02), and 1.34 (0.94-1.90; P = 0.08), respectively, after adjustment for age, body mass index, smoking status, alcohol drinking habits, history of diabetes, use of antihypertensives, work category, and total energy intake. With each 100-g/day increase in consumption of milk and dairy products, HRs tended to decrease for deaths from CVD (HR, 0.86; 95% CI, 0.74-0.99), CHD (0.73; 0.52-1.03), and stroke (0.81; 0.65-1.01) in women. No significant association was observed in men. CONCLUSIONS: Consumption of milk and dairy products was inversely associated with CVD death among women in Japan.

Prospective Study on Waist Circumference and Risk of All-Cause and Cardiovascular Mortality - Pooled Analysis of Japanese Community-Based Studies

Isao Saito, Yoshihiro Kokubo, Yutaka Kiyohara, Yasufumi Doi, Shigeyuki Saitoh, Hirofumi Ohnishi, Yoshihiro Miyamoto

CIRCULATION JOURNAL ( JAPANESE CIRCULATION SOC ) 76 ( 12 ) 2867 - 2874 2012年12月 [査読有り]

Background: The aim of the present study was to clarify the association between waist circumference and all-cause and cardiovascular disease (CVD) mortality risk in relatively lean Japanese subjects. Methods and Results: A total of 3,554 men and 4,472 women who had no history of CVD were examined and their waist circumference measured at baseline. The subjects were aged >= 10 years and were obtained from 3 prospective cohort studies during 1988-1996. Hazard ratios for all-cause and CVD mortality were analyzed over a follow-up period Of 14.7 years using a Cox proportional hazards model and penalized spline method, after adjustment for study cohort, age, smoking, alcohol drinking, hypertension, dyslipidemia, and diabetes. Compared with the lowest quintile, the highest quintile of waist circumference in men was associated with a linear reduction in all-cause mortality risk (multivariate-adjusted hazard ratio, 0.73; 95% confidence interval: 0.60-0.89; P for trend=0.001). CVD mortality risk was increased in men aged 65 years with a higher waist circumference. This relationship was U-shaped. Waist circumference was not associated with all-cause or CVD mortality risk in women. Conclusions: Waist circumference was associated inversely with increased risk of all-cause death in men, but not in women. Middle-aged men with a greater waist circumference potentially have an increased risk of CVD mortality. (Circ J 2012; 76: 2867-2874)

Effects of Parental Hypertension on Longitudinal Trends in Blood Pressure and Plasma Metabolic Profile Mixed-Effects Model Analysis

Kaneto Mitsumata, Shigeyuki Saitoh, Hirofumi Ohnishi, Hiroshi Akasaka, Tetsuji Miura

HYPERTENSION ( LIPPINCOTT WILLIAMS & WILKINS ) 60 ( 5 ) 1124 - + 2012年11月 [査読有り]

The mechanism underlying the association of parental hypertension with cardiovascular events in offspring remains unclear. In this study, the effects of parental hypertension on longitudinal trends of blood pressure and metabolic parameters were examined by mixed-effects model analysis. From 1977 to 2006, 5198 subjects participated in the Tanno-Sobetsu Study, and we selected 2607 subjects (1095 men and 1512 women) for whom data on parental history of hypertension were available. In both men and women with and without parental hypertension, systolic blood pressure and fasting blood glucose levels consistently increased from the third to eighth decades of life, whereas diastolic blood pressure and serum triglyceride levels followed biphasic (inverted U shape) time courses during that period. However, the relationships between the parameters and age were significantly shifted upward (by approximate to 5.3 mm Hg in systolic blood pressure, 2.8 mm Hg in diastolic blood pressure, 0.30 mmol/L in blood glucose, and 0.09 mmol/L in triglyceride) in the group with parental hypertension compared with those in the group without parental hypertension. Both paternal and maternal histories of hypertension were determinants of systolic blood pressure and diastolic blood pressure, and there was no significant interaction between the sides of parental history. There were no significant effects of parental hypertension on age-dependent or body mass index-dependent changes in serum low-density lipoprotein cholesterol or high-density lipoprotein cholesterol level. The present results indicate that parental hypertension has an age-independent impact on elevation of blood pressure, plasma glucose, and triglyceride levels, which may underlie the reported increase in cardiovascular events by family history of hypertension. (Hypertension. 2012;60:1124-1130.). Online Data Supplement

Burden among Family Caregivers of Patients on Chronic Hemodialysis in Northern Japan

Masakazu Washio, Hideaki Yoshida, Nobuyuki Ura, Hirofumi Ohnishi, Nobuhiko Togashi, Fumio Sakauchi, Yumiko Arai, Mitsuru Mori, Kazuaki Shimamoto

INTERNATIONAL MEDICAL JOURNAL ( JAPAN INT CULTURAL EXCHANGE FOUNDATION ) 19 ( 3 ) 221 - 223 2012年09月 [査読有り]

Purpose: To investigate factors related to burden among family caregivers of regular hemodialysis patients. Design: Cross sectional study. Subjects: 108 pairs of family caregivers and regular hemodialysis patients in Hokkaido Prefecture, Japan. Subjects and Methods: Caregivers answered a self-administered questionnaire about various factors that may affect their care-burden and also completed the Japanese version of the Zarit careburden interview (J-ZBI). They were divided into two groups according to their ZBI score. Results: Compared with lightly burdened caregivers, those heavily burdened were more likely to be spouses and to have chronic diseases under medical treatment. Patients cared for by heavily burdened caregivers were more likely to be males, have dementia, and be disabled than their counterparts. Heavily burdened caregivers spent a longer time with their charges as well as in providing for their physical care than lightly burdened caregivers. In addition, they spent more money to use social services in their caregiving than lightly burdened caregivers. Heavily burdened caregivers were more likely to rent wheelchairs, to consult a staff of a support center for the frail elderly, to consult a home doctor, to use home renovation services, to apply to the insurer for the assessment of need for care, and to make a care plan than their counterparts. Compared with lightly burdened caregivers, more of those heavily burdened wanted regular assistance for care and facilities for regular day-time respite care. Conclusion: These findings suggest that looking after patients for a long time as well as paying a lot of money seems to be an important factor related to caregiver's developing psychological feelings of heavy burden.

Relationship of Hobby Activities With Mortality and Frailty Among Community-Dwelling Elderly Adults: Results of a Follow-up Study in Japan

Yasuhiro Fushiki, Hirofumi Ohnishi, Fumio Sakauchi, Asae Oura, Mitsuru Mori

JOURNAL OF EPIDEMIOLOGY ( JAPAN EPIDEMIOLOGICAL ASSOC ) 22 ( 4 ) 340 - 347 2012年07月 [査読有り]

Background: The proportion of Japanese adults aged 65 years or older is predicted to increase; thus, it is becoming more important to identify factors that influence health status among elderly adults in Japan. We conducted a follow-up study of community-dwelling elderly adults to assess the relationship of hobby activities with mortality and incident frailty. Methods: We randomly selected 3583 individuals aged 65 to 84 years from the residential registries of 7 study areas in Hokkaido, Japan in August 2007. Among them, 1955 (54.6%) returned completed questionnaires with written informed consent by mail. The baseline assessment questionnaire comprised questions on current and past involvement in hobby activities, self-perceived health status, smoking and drinking habits, and body height and weight. Questions on hobby activities were from 4 categories: solitary physical, group physical, solitary cultural, and group cultural activities. We later conducted a follow-up survey of the participants to ascertain all-cause mortality and incident frailty. A Cox proportional hazards model was used for analysis of data from September 2007 to May 2010. Results: After adjusting for potential confounders, the risk of incident frailty among respondents participating in solitary physical activities was significantly lower than in those who did not participate in such activities (hazard ratio = 0.57; 95% CI 0.33, 0.99). Furthermore, the risk of incident frailty among respondents taking part in group cultural activities was significantly lower than in those who did not participate in such activities (0.41; 0.19, 0.87). Conclusions: These findings may be important for programs that seek to promote good health among elderly adults.

Relationship between dysphagia and depressive states in patients with Parkinson's disease

Meng Han, Hirofumi Ohnishi, Michio Nonaka, Rika Yamauchi, Takayoshi Hozuki, Takashi Hayashi, Masaki Saitoh, Shin Hisahara, Tomihiro Imai, Shun Shimohama, Mitsuru Mori

Parkinson's Disease: Diagnosis, Treatment and Prognosis 201 - 208 2012年07月

Aspiration pneumonia related to dysphagia is known to be the leading cause of death in patients with Parkinson's disease (PD). We investigated the relationship between depressive states and dysphagia in patients with PD. A hundred and twenty-seven PD patients gave their informed consent and were enrolled in this study. We used the Beck Depression Inventory II (BDI-II) questionnaire to determine the participants' depressive states, and also used a questionnaire to assess participants' state of dysphagia. Participants were divided into four groups according to their BDI-II score. We compared the PD patients with Swallowing Disturbances Questionnaire (SDQ) scores of more than or equal to 11 with the SDQ scores of less than 11 regarding depressive categories. A logistic regression analysis was conducted to calculate odds ratios (ORs) and their 95% confidence intervals (95%CI) adjusting for age, sex, disease duration, wearing-off phenomenon and severity of movement disorder. OR (95%CI) of depressive categories,in which the trivial class was set as a reference group, were 3.28 (0.93-11.55), 13.44 (3.10-58.16), 30.35 (5.65-162.97) in the mild class, the moderate class and the severe class, respectively. This study suggests that there may be a strong relationship between depressive states and dysphagia in patients with PD. © 2012 Nova Science Publishers, Inc. All rights reserved.

[The Tanno and Sobetsu study].

Ohnishi H, Saitoh S, Miura T

Nihon rinsho. Japanese journal of clinical medicine 70 Suppl 3 260 - 263 2012年05月 [査読有り]

Matsuda-DeFronzo insulin sensitivity index is a better predictor than HOMA-IR of hypertension in Japanese: the Tanno-Sobetsu study

M. Furugen, S. Saitoh, H. Ohnishi, H. Akasaka, K. Mitsumata, M. Chiba, T. Furukawa, Y. Miyazaki, K. Shimamoto, T. Miura

JOURNAL OF HUMAN HYPERTENSION ( NATURE PUBLISHING GROUP ) 26 ( 5 ) 325 - 333 2012年05月 [査読有り]

Here we examined whether the Matsuda-DeFronzo insulin sensitivity index (ISI-M) is more efficient than the homeostasis model assessment of insulin resistance (HOMA-IR) for assessing risk of hypertension. Cross-sectional and longitudinal analyses were conducted using normotensive subjects who were selected among 1399 subjects in the Tanno-Sobetsu cohort. In the cross-sectional analysis (n = 740), blood pressure (BP) level was correlated with HOMA-IR and with ISI-M, but correlation coefficients indicate a tighter correlation with ISI-M. Multiple linear regression analysis adjusted by age, sex, body mass index (BMI) and serum triglyceride level (TG) showed contribution of ISI-M and fasting plasma glucose, but not of HOMA-IR. In the longitudinal analysis (n = 607), 241 subjects (39.7%) developed hypertension during a 10-year follow-up period, and multiple logistic regression indicated that age, TG, systolic BP and ISI-M, but not HOMA-IR, were associated with development of hypertension. In subjects <60 years old, odds ratio of new-onset hypertension was higher in the low ISI-M group (ISI-M, less than the median) than in the high ISI-M group for any tertile of BMI. In conclusion, ISI-M is a better predictor of hypertension than is HOMA-IR. Non-hepatic IR may be a determinant, which is independent of TG, BP level and BMI, of the development of hypertension. Journal of Human Hypertension (2012) 26, 325-333; doi:10.1038/jhh.2011.23; published online 17 March 2011

Association between salivary alpha-amylase activity and stress-related characteristics

Yoshie Nagata, Fumio Sakauchi, Hisako Izumi, Erhua Shang, Hirofumi Ohnishi, Mitsuru Mori

Sapporo Medical journal 80 ( 1-6 ) 15 - 22 2011年12月

Introduction: Recently, salivary alpha-amylase activity has been suggested to be an index as a stress-related biomarker. In this study, we investigated possible associations between salivary alpha-amylase activity levels and lifestyle or stress-related characteristics. Methods: In total, 476 subjects voluntarily participated in the survey and their levels of salivary amylase activity were measured by a noninvasive salivary amylase monitor. Every subject filled out a self-administered questionnaire just after the measurement. Results: The results of these tests indicate the salivary alpha-amylase activity levels are significantly higher in males than those in females (P< 0.01). Furthermore, the salivary alpha-amylase activity levels were significantly higher in the subjects aged 50 years or older than those of the subjects aged younger than 50 years (P< 0.01). Scores of the behaviors of positively coping with stress as well as social support from relatives or friends against stress were inversely correlated to salivary alpha-amylase activity after being adjusted for sex and age with multiple linear regression analysis (P=0.02 and P=0.03, respectively). However, the perception of stress was not associated with changes in salivary alpha-amylase activity levels. Conclusion: Our findings may suggest that positively stress coping and emotional supports reduce the physiological response to stress, as observed by the decrease in salivary alpha-amylase activity levels.

Relationship between dysphagia and depressive states in patients with Parkinson's disease

Meng Han, Hirofumi Ohnishi, Michio Nonaka, Rika Yamauchi, Takayoshi Hozuki, Takashi Hayashi, Masaki Saitoh, Shin Hisahara, Tomihiro Imai, Shun Shimohama, Mitsuru Mori

PARKINSONISM & RELATED DISORDERS ( ELSEVIER SCI LTD ) 17 ( 6 ) 437 - 439 2011年07月 [査読有り]

Aspiration pneumonia related to dysphagia is known to be the leading cause of death in patients with Parkinson's disease (PD). We investigated the relationship between depressive states and dysphagia in patients with PD. A hundred and twenty-seven PD patients gave their informed consent and were enrolled in this study. We used the Beck Depression Inventory (BDI) questionnaire to determine the participants' depressive states, and also used a questionnaire to assess participants' state of dysphagia. Participants were divided into four groups according to their BDI score. We compared the PD patients with Swallowing Disturbances Questionnaire (SDQ) scores of more than or equal to 11 with the SDQ scores of less than 11 regarding depressive categories. A logistic regression analysis was conducted to calculate odds ratios (ORs) and their 95% confidence intervals (95%CI) adjusting for age, sex, disease duration, wearing-off phenomenon and severity of movement disorder. OR (95%CI) of depressive categories, in which the trivial class was set as a reference group, were 3.28 (0.93-11.55), 13.44(3.10-58.16), 30.35 (5.65-162.97) in the mild class, the moderate class and the severe class, respectively. This study suggests that there may be a strong relationship between depressive states and dysphagia in patients with PD. (C) 2011 Elsevier Ltd. All rights reserved.

Comparison of the effect of abdominal obesity on new onset of type 2 diabetes in a general Japanese elderly population with that in a non-elderly population-The Tanno and Sobetsu study

Mizue Fujii, Hirofumi Ohnishi, Shigeyuki Saitho, Mitsuru Mori, Kazuaki Shimamoto

Japanese Journal of Geriatrics ( 1 ) 48 ( 1 ) 71 - 77 2011年 [査読有り]

Aim: We investigated the effect of abdominal obesity (AO) on new onset of type 2 diabetes (NODM) in a general Japanese elderly population compared with that in a non-elderly population. Methods: The subjects were 827 people aged 29-84 who underwent medical examinations in the towns of Tanno and Sobetsu in Hokkaido, first in 1994 and subsequently in either 2003 or 2004, after the exclusion of individuals with preexisting type 2 diabetes at baseline. The subjects were divided into 2 groups according to waist circumference (WC) at baseline: an AO (WC ≥85 cm for men and ≥90 cm for women) group and a non-AO group. The percentages of subjects with NODM recorded in either in 2003 or 2004 were compared between these 2 groups, and the AO odds ratio in NODM was calculated separately for elderly (≤65 years) and non-elderly (< 65 years) subjects, using multiple logistic regression analysis. Results: The percentage of non-elderly subjects with NODM was significantly higher in the AO group than in the non-AO group (16.9% vs. 5.4%, p< 0.0001), but there was no statistically significant difference in the elderly subjects. Multiple logistic regression analysis showed that there was a significant relationship between AO and NODM (AO odds ratio in NODM= 2.68, 95% confidence interval (CI): 1.05-6.90) in the non-elderly subjects, but not in the elderly subjects. Conclusion: Consideration of the different effects of AO on NODM in elderly and non-elderly people may be important for the prevention of type 2 diabetes.

Associations of metabolic factors, especially serum retinol-binding protein 4 (RBP4), with blood pressure in Japanese -the Tanno and Sobetsu study-

Mizue Chiba, Shigeyuki Saitoh, Hirofumi Ohnishi, Hiroshi Akasaka, Kaneto Mitsumata, Tetsuaki Furukawa, Kazuaki Shimamoto

ENDOCRINE JOURNAL ( JAPAN ENDOCRINE SOC ) 57 ( 9 ) 811 - 817 2010年09月 [査読有り]

Excess secretion of various adipocyte-derived molecules has been linked with insulin resistance, obesity, diabetes, inflammation, atherosclerosis, and cardiovascular disease. Retinol-binding protein 4 (RBP4), one of the new adipocytokine, is recently reported to provide a link between insulin resistance and features of metabolic factors. Hypertension is one of the most influential risk factors among cardiovascular disease. We examined the relationship between systolic blood pressure (BP) levels and metabolic factors including homeostasis model assessment of insulin resistance (HOMA-R), high sensitivity C-reactive protein (hs-CRP), adiponectin, and RBP4. The subjects were 153 men aged 59 +/- 14 years and 224 women aged 57 +/- 14 years who had undergone medical check-ups in rural communities in 2007. Systolic BP was positively correlated with HOMA-R, hs-CRP and RBP4 but not with adiponectin in women. There was a positive significant relationship between serum RBP4 levels and blood pressure in women, but such a relationship was not found in men. Serum RBP4 levels were not correlated with HOMA-R in either men or women. Serum RBP4 levels negatively were correlated with estimated glomerular filtration rate (eGFR) in women but not in men. Multiple regression analysis revealed that serum RBP4 levels significantly were related to systolic BP independently of age, sex, body mass index (BMI), total cholesterol levels and eGFR. Our study showed that increased levels of RBP4 as well as HOMA-R and hs-CRP in women were significantly associated with increased levels of systolic BP.

Total energy intake and intake of three major nutrients by body mass index in Japan: NIPPON DATA80 and NIPPON DATA90

Katsushi Yoshita, Yusuke Arai, Miho Nozue, Kumi Komatsu, Hirohumi Ohnishi, Shigeyuki Saitoh, Katsuyuki Miura

Journal of Epidemiology 20 ( 3 ) S515 - S523 2010年 [査読有り]

Background: This paper investigated the relationship between body mass index (BMI) and total energy intake as well as intake of three major nutrients in representative Japanese populations enrolled in the National Nutrition Surveys of Japan in 1980 and 1990. Methods: A total of 10 422 participants (4585 men and 5837 women) and 8342 participants (3488 men and 4854 women) aged 30 or older from 300 randomly selected districts participated in the National Survey of Circulatory Disorders and the National Nutrition Survey in Japan in 1980 and 1990, respectively. The nutrition surveys were performed with weighing record method for three consecutive days to each household. Individually estimated total energy intake and intakes of three major nutrients (carbohydrate, protein, and fat) were compared by the categories of BMI and by 10-year age groups. Results: In men, total energy intake (kcal/day), intakes of three major nutrients (g/day) and energy intake ratio from protein and fat (%) increased as BMI increased in each age group, whereas energy intake ratio from carbohydrate (%) decreased. In women, total energy intake, intakes of three major nutrients, and energy intake ratio from protein increased as BMI increased. Energy intake ratio from carbohydrate and fat decreased as BMI increased in women in 1990. When participants were categorized into quartiles according to total energy intake in each sex group, BMI increased as total energy intake increased in men in both 1980 and 1990. Conclusions: A positive relationship was observed between body mass index and total energy intake in Japanese men. The relationship was weaker in Japanese women. © 2010 by the Japan Epidemiological Association.

過体重の健常者における心房内電気力学的遅延と左心房機能の変化 2次元Speckle Tracking画像の検討(Alterations in Intra-atrial Electromechanical Delay and Left Atrial Function in Healthy Overweight Subjects: A Study of Two-dimensional Speckle Tracking Imaging)

Muranaka Atsuko, Yuda Satoshi, Funayama Maki, Yamamoto Hitomi, Kohzu Hidemichi, Doi Takahiro, Kaneko Naofumi, Akasaka Hiroshi, Ohnishi Hirofumi, Shimoshige Shinya, Hashimoto Akiyoshi, Saitoh Shigeyuki, Nakata Tomoaki, Tsuchihashi Kazufumi, Watanabe Naoki, Shimamoto Kazuaki

Circulation Journal ( (一社)日本循環器学会 ) 73 ( Suppl.I ) 702 - 702 2009年03月

Traditional Japanese diet and prostate cancer

Mitsuru Mori, Naoya Masumori, Fumimasa Fukuta, Yoshie Nagata, Tomoko Sonoda, Fumio Sakauchi, Hirofumi Ohnishi, Masanori Nojima, Taiji Tsukamoto

MOLECULAR NUTRITION & FOOD RESEARCH ( WILEY-V C H VERLAG GMBH ) 53 ( 2 ) 191 - 200 2009年02月 [査読有り]

The traditional Japanese diet has been suggested by some researchers to be associated with a decreased risk of prostate cancer (PCa). In this paper, we assumed the following three characteristics of the traditional Japanese diet high in soybean products, high in fish, and low in red meat. Isoflavones, polyunsaturated long chain (n - 3) fatty acids, and saturated fatty acids were thought to be micronutrients in biological etiology relevant to soybean products, fish, and red meat, respectively. Analytical epidemiological studies oil the risk of PCa were identified using the MEDLINE database from 1998 to 2007. Some published studies showed a negative association of soybean products and isoflavones to PCa risk, an inverse association for fish or polyunsaturated long chain (n - 3) fatty acids such as eicosapentaenic acid (EPA) and docosahexacnoic acid (DHA) with PCa risk, and a positive association of red meat or saturated fatty acids with PCa risk, respectively. In conclusion, although it is possible that the traditional Japanese diet may reduce the risk of PCa through a combination of characteristics such as being high in soybean products, high in fish, and low in red meat, further well-designed epidemiological studies such as nested case-control studies with nutritional analyses of blood samples are needed to confirm this association.

A Promoter Polymorphism of Lamin A/C Gene is an Independent Genetic Predisposition to Arterial Stiffness in a Japanese General Population (The Tanno and Sobetsu Study)

Hiroshi Akasaka, Tomohiro Katsuya, Shigeyuki Saitoh, Ken Sugimoto, Hirofumi Ohnishi, Ada Congrains, Miyuki Ohnishi, Mitsuru Ohishi, Hiromi Rakugi, Toshio Ogihara, Kazuaki Shimamoto

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS ( JAPAN ATHEROSCLEROSIS SOC ) 16 ( 4 ) 404 - 409 2009年 [査読有り]

Aim: We examined the hypothesis that there is a positive, independent association between polymorphisms of lamin A/C gene (LMNA) and arterial stiffness in Japanese. Methods: The subjects were 261 men (mean age, 64.4 +/- 0.7 years) selected from inhabitants of the towns of Tanno and Sobetsu in a rural area of Japan who underwent medical check-ups. We conducted clinical examinations, including measurement of bilateral brachial-ankle pulse wave velocity (baPWV) as a marker of arterial Stiffness, and genetic analysis. Subjects with atrial fibrillation, subjects with ankle-brachial index < 0.9, and subjects taking any medication were excluded. We selected two single nucleotide polymorphisms (SNPs) as markers of LMNA, 1908C/T in exon 10 and -1030C/T in the promoter region, which we have recently identified. All genotypes were clearly determined by the TaqMan PCR method. Results: Genotype frequencies of the two polymorphisms satisfied the Hardy-Weinberg equilibrium. The baPWV of -1030C/T polymorphism was significantly greater in subjects with CC genotype than in subjects with CT + TT genotype (1,652 +/- 22.1 cm/s vs. 1,552 +/- 43.0 cm/s, p = 0.039); however, no significant difference was found for 1908C/T polymorphism. The baPWV was found to be significantly associated with age, body height, systolic blood pressure, and smoking habit; therefore, we next performed multiple regression analysis including these parameters, and found an independent, significant association between baPWV and -1030C/T polymorphism. Conclusion: Promoter -1030C/T polymorphism of LMNA is a possible genetic predisposition to arterial stiffness in the Japanese population.

Increased Serum Apolipoprotein B48 Concentration in Patients with Metabolic Syndrome

Makoto Kinoshita, Hirofumi Ohnishi, Tomomi Maeda, Nakayuki Yoshimura, Yoko Takeoka, Daijiro Yasuda, Jun Kusano, Yamato Mashimo, Shigeyuki Saito, Kazuaki Shimamoto, Tamio Teramoto

JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS ( JAPAN ATHEROSCLEROSIS SOC ) 16 ( 4 ) 517 - 522 2009年 [査読有り]

Aim: Postprandial hyperlipidemia is characterized by an increase of chylomicron remnants (CM-R), and is a risk factor for atherosclerosis. Apolipoprotein (apo) B48 exists exclusively in chylomicroms and CM-R, and fasting plasma levels of apo B48 may reflect high postprandial levels of chylomicrons and/or CM-R. We hypothesized that fasting apo B48 levels may be increased in metabolic syndrome. Methods: We investigated 1,349 inhabitants (528 men and 821 women aged 62.4 +/- 12.8 y; mean +/- S.D.) of two towns in rural Hokkaido, who underwent health checks in 2005. Results: The fasting apo B48 level was significantly higher in males than females (geometric mean 1.92; 95% CI 1.80-2.04 mu g/mL, vs. 1.69; 95% CI 1.61-1.76 mu g/mL; p<0.001). Ln (apo B48) showed a significant positive correlation with total cholesterol and In (triglycerides), and a negative correlation with HDL-cholesterol. The correlation between In (apo 1348) and In (triglycerides) was strong. Apo B48 was significantly higher in men and women with than without metabolic syndrome. Regression analysis revealed that In (apo B48) was significantly associated with age, BMI total cholesterol, HDL cholesterol, LDL cholesterol, and In (triglyceride). Conclusion: Fasting apo B48 levels are raised in individuals with metabolic syndrome.

Confounding in evaluating the effectiveness of influenza vaccine

Mitsuru Mori, Asae Oura, Hirofumi Ohnishi, Masakazu Washio

VACCINE ( ELSEVIER SCI LTD ) 26 ( 50 ) 6459 - 6461 2008年11月 [査読有り]

Confounding is a kind of bias which occurs in a research. Confounding is less frequent in randomized controlled trials (RCT) for evaluation of influenza vaccines. However, there are obstacles or difficulties in conducting RCT for evaluation of influenza vaccines, particularly, in the elderly people. Therefore a retro, spective or prospective cohort study has been primarily performed to evaluate effectiveness of influenza vaccine in elderly people. Confounding by indication or other confounding exist in most observational Studies. Accordingly, at the stage of designing or analyzing a study, confounding should be controlled with a restriction, matching, stratified or multivariate analysis technique. (C) 2008 Elsevier Ltd. All rights reserved.

パーキンソン病患者のADLとQOLに対する抑うつの影響

韓萌, 大西浩文, 森満, 林貴士, 久原真, 野中道夫, 今井富裕, 下濱俊

北海道公衆衛生学雑誌 ( 北海道公衆衛生学会 ) 22 ( 1特別付録 ) 65 - 65 2008年11月

未治療高血圧患者における心形態および心機能の評価組織ドプラ法による検討端野・壮瞥町研究

舟山真希, 湯田聡, 村中敦子, 山本均美, 金子尚史, 土井崇裕, 神津英至, 赤坂憲, 大西浩文, 下重晋也, 橋本暁佳, 斉藤重幸, 土橋和文, 渡辺直樹, 島本和明

日本高血圧学会総会プログラム・抄録集 ( (NPO)日本高血圧学会 ) 31回 200 - 200 2008年10月

Differences in Insulin Action and Secretion, Plasma Lipids and Blood Pressure Levels between Impaired Fasting Glucose and Impaired Glucose Tolerance in Japanese Subjects

Yoshinori Miyazaki, Hiroshi Akasaka, Hirofumi Ohnishi, Shigeyuki Saitoh, Ralph A. DeFronzo, Kazuaki Shimamoto

HYPERTENSION RESEARCH ( JAPANESE SOC HYPERTENSION CENT ACADEMIC SOC, PUBL OFFICE ) 31 ( 7 ) 1357 - 1363 2008年07月 [査読有り]

We examined insulin action/secretion and cardiovascular disease risk factors in Japanese subjects with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) who were not taking any medications known to affect glucose tolerance, blood pressure (1313) or plasma lipids (PLs). A total of 1,399 subjects received measurements of anthropometry, BP, PLs, and plasma glucose/insulin concentrations during 75 g-oral glucose tolerance test (OGTT). According to 2003 American Diabetes Association criteria, subjects were classified as having normal fasting glucose (NFG)/normal glucose tolerance (NGT) (n=1,173), IFG (n=128), IGT (n=55), and IFG/IGT (n=43). Insulin action was calculated using the HOMA-R (index of hepatic insulin resistance) and Matsuda index (reflects whole body insulin sensitivity). The ratio of the incremental area under the curve of insulin to that of glucose during OGTT (Delta AUC(PI)/Delta AUC(PG)) was used as an index of beta-cell function. HOMA-R was higher in IFG (2.3 +/- 0.1) and IFG/IGT (2.5 +/- 0.2) than in NFG/NGT (1.8 +/- 0.03). The Matsuda index was lower in IFG (6.5 +/- 0.3), IGT (5.4 +/- 0.4) and IFG/IGT (5.1 +/- 0.5) than in NFG/NGT (9.6 +/- 0.2).,Delta AUC(PI)/Delta AUC(PG) was lower in IGT (0.6 +/- 0.05) and IFG/IGT (0.5 0.05) than in IFG (1.4 +/- 0.12) or NFG/NGT (1.2 +/- 0.03). Mean BP was higher in IGT (100 +/- 1.7 mmHg) than in NFG/NGT (91 +/- 0.3) or IFG (95 +/- 1.1). The plasma triglyceride level was higher in IGT (155 +/- 14 mg/dL) and IGTAFG (173 12) than in IFG (132 +/- 7) or NFG/NGT (122 +/- 2). In conclusion, 1) whole body insulin sensitivity is decreased in IFG and IGT, with a greater reduction in IGT, 2) hepatic insulin resistance and preserved beta-cell function are characteristics of IFG, and 3) higher BP and triglyceride levels are observed in IGT. IGT is more closely associated with risk factors for cardiovascular disease than is IFG. (Hypertens Res 2008; 31: 1357-1363)

Incidence of Hypertension in Individuals with Abdominal Obesity in a Rural Japanese Population: The Tanno and Sobetsu Study

Hirofumi Ohnishi, Shigeyuki Saitoh, Hiroshi Akasaka, Kaneto Mitsumata, Mizue Chiba, Makoto Furugen, Tetsuaki Furukawa, Mitsuru Mori, Kazuaki Shimamoto

HYPERTENSION RESEARCH ( JAPANESE SOC HYPERTENSION CENT ACADEMIC SOC, PUBL OFFICE ) 31 ( 7 ) 1385 - 1390 2008年07月 [査読有り]

Although abdominal obesity (AO) assessed by waist circumference (WC) is an important component of the metabolic syndrome (MetS), the usefulness of AO as a predictor of hypertension (HT) is not known. In this study, we investigated the incidence of HT in residents of two rural communities in Japan. The subjects were 187 men and 209 women selected from 712 residents who had undergone medical examinations in the towns of Tanno and Sobetsu, Hokkaido, in 1994 and 2002. Participants with HT in 1994 were excluded. Participants with AO were determined according to the WC criteria in the Japanese definition of MetS ( 85 cm for men, >= 90 cm for women). The participants were divided into two groups: a non-AO group and an AO group. We compared the incidence of HT between the two groups and found a significantly higher incidence in the AO group. The results of logistic regression analysis showed that the relative risk of developing HT in individuals with AO was 2.33 (p=0.017; 95% confidence interval [CI], 1.17-4.63) and that the risk per 1-cm increase in WC from 1994 to 2002 was 1.06 (p=0.003; 95% Cl, 1.02-1.10), both adjusted for several confounding factors. The results of this study suggest that, to prevent HT in Japanese, it is important to manage abdominal obesity and to monitor WC in individuals with or without abdominal obesity. (Hypertens Res 2008; 31: 1385-1390)

Comparison of the clinical features of Japanese patients with primary biliary cirrhosis in 1999 and 2004: Utilization of clinical data when patients applied to receive public financial aid

Fumio Sakauchi, Asae Oura, Hirofumi Ohnishi, Mitsuru Mori

Journal of Epidemiology 17 ( 6 ) 210 - 214 2007年12月 [査読有り]

Background: In Asia there are few reports considering time intervals in the examination of clinical features of primary biliary cirrhosis (PBC). Therefore, we tried to compare the characteristics of patients with PBC in two different years. Methods: In two fiscal years (1999 and 2004), 9,761 and 13,142 patients with symptomatic PBC were registered to receive public financial aid from the Ministry of Health, Labour and Welfare of Japan, respectively. For the present study, clinical data from 2,127 patients in 1999 and 6,423 ones in 2004 were available. We compared the data in the two different years, including sex, age, major symptoms, and laboratory data. Results: Male/female ratios were the same figure (0.13 for 1999 and 2004). The median age was significantly older in 2004 than in 1999 (59 years for 1999, 63 years for 2004, respectively, p< 0.01). Jaundice and esophageal varices were found significantly less frequent in 2004 than in 1999 (p< 0.01 for each item). Levels of total bilirubin, γ-glutamyl transpeptidase (γ-GTP), total cholesterol, and immunoglobulin M were significantly lower in 2004 than in 1999 (p< 0.02 for total bilirubin, and p< 0.01 for other each item). The positive rate of antimitochondrial antibodies was significantly higher in 1999 than in 2004 (87.0% for 1999, 83.5% for 2004, respectively, p< 0.01)). Complicated autoimmune diseases such as Sjögren's syndrome, rheumatoid arthritis, and chronic thyroiditis were found significantly more frequent in 2004 than in 1999 (p< 0.01 for each item). Conclusions: Among the patients with PBC in 2004, an increase in median age, and lower levels of laboratory data such as γ-GTP have been found compared to 1999. These results may show an accumulation of patients with better prognosis and the recent medical progress in controlling patients with PBC. Copyright © 2007 by the Japan Epidemiological Association.

慢性腎疾患とメタボリックシンドロームの関連の検討端野・壮瞥町研究

赤坂憲, 浦信行, 斎藤重幸, 大西浩文, 吉田英昭, 伊藤洋輔, 田中希尚, 三俣兼人, 島本和明

日本腎臓学会誌 ( (一社)日本腎臓学会 ) 49 ( 3 ) 282 - 282 2007年04月

加速度センサー装置での身体活動量測定と身体活動と関連する要因の検討

森満, 尚爾華, 和泉比佐子, 坂内文男, 大西浩文, 長多好恵, 岡野五郎, 小林幸太, 檜垣靖樹

北海道公衆衛生学雑誌 20 ( 2 ) 72 - 77 2007年03月

Relationship between visceral fat and cardiovascular disease risk factors: The Tanno and Sobetsu study

Yu Chiba, Shigeyuki Saitoh, Satoru Takagi, Hirofumi Ohnishi, Nobuo Katoh, Junichi Ohata, Motoya Nakagawa, Kazuaki Shimamoto

HYPERTENSION RESEARCH ( JAPANESE SOC HYPERTENSION CENT ACADEMIC SOC, PUBL OFFICE ) 30 ( 3 ) 229 - 236 2007年03月 [査読有り]

We assessed the amount of visceral fat using ultrasonography (US) and studied its relationship to cardiovascular disease risk factors, particularly blood pressure. The subjects in the first study were 45 male and 61 female outpatients. We measured the visceral fat area (VFA) of each subject using abdominal CT and waist circumference (WC), and visceral fat distance (VFD) using US. The subjects in the second study were 353 male and 457 female inhabitants of a rural community, for whom VFD and WC were measured. We divided subjects into tertiles based on VFD and WC, and studied the relationship between each group and individual risk factors. In an analysis of outpatient subjects, the correlation coefficient between VFA and VFD was satisfactory: r=0.660 for men and r=0.643 for women. In the analysis of the rural subjects, the high VFD group had a significantly higher odds ratio than the low VFD group in high blood pressure (HBP) and hypertriglyceridemia (HTG) for men and in HBP, HTG and low high-density lipoprotein cholesterolemia (LHDL) for women. Moreover, adjusting VFD for body mass index revealed that, in comparison to WC, VFD was significantly related to risk factors. VFD was used as an independent variable in multiple regression analysis with blood pressure level as a dependent variable; no significant association between WC and blood pressure was obtained. Visceral fat assessment by US may be useful for epidemiological study and for clinics with no abdominal CT equipment for identifying high-risk individuals, such as those with metabolic syndrome.

Impact of abnormal glucose tolerance, hypertension and other risk factors on coronary artery disease

Yosuke Nakamura, Shigeyuki Saitoh, Satoru Takagi, Hirofumi Ohnishi, Yu Chiba, Nobuo Kato, Hiroshi Akasaka, Tetsuji Miura, Kazufumi Tsuchihashi, Kazuaki Shimamoto

Circulation Journal ( 1 ) 71 ( 1 ) 20 - 25 2007年 [査読有り]

Background: The degree to which abnormal glucose tolerance contributes to the development of coronary artery disease (CAD) has not been clarified in Japanese. The relationship between abnormal glucose tolerance and severity of coronary artery stenosis, as well as the contributions of hypertension, diabetes and other risk factors for CAD to recurrence of the disease, were investigated in the present study. Methods and Results: The subjects were 474 consecutive patients (mean age: 63.8±11.3 years) with suspected CAD who were admitted to Sapporo Medical University Hospital during April 1, 1997 to March 31, 2004. The coronary index and stenosis score were higher in subjects with diabetes mellitus (DM) and in subjects with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) than in subjects with normal glucose tolerance (NGT). Ischemic episodes recurred during the observation period (mean 2.5 years) in 61 of 341 patients diagnosed as having CAD. In the follow-up subjects, systolic blood pressure (SBP) was significantly higher in the recurrence group than in the non-recurrence group, and SBP was a significant variable in logistic regression analysis after adjustment for age, gender, hemoglobin A1c, total cholesterol, body mass index, smoking history, family history and stenosis score. The relative risk of recurrence became 1.7-fold higher with a rise in SBP of 10 mmHg (95% confidence interval: 1.252-2.250). Analysis of the relationship between glucose tolerance and recurrence showed that the rate of recurrence was higher in patients with IFG+IGT+DM than in those with NGT. Conclusions: CAD progresses not only in patients with DM but also in those with IGT. The rate of recurrence of ischemic episodes increases in individuals with IGT or DM, and suggesting that hypertension is a risk factor for recurrence of ischemic episodes. Management of glucose tolerance and blood pressure is therefore important for prevention of CAD in Japanese.

Effects of angiotensin II type 1 receptor gene polymorphisms on insulin resistance in a Japanese general population: the Tanno-Sobetsu study.

Hiroshi Akasaka, Tomohiro Katsuya, Shigeyuki Saitoh, Ken Sugimoto, Yuxiao Fu, Satoru Takagi, Hirofumi Ohnishi, Hiromi Rakugi, Nobuyuki Ura, Kazuaki Shimamoto, Toshio Ogihara

Hypertension research : official journal of the Japanese Society of Hypertension ( 12 ) 29 ( 12 ) 961 - 7 2006年12月 [査読有り] [国際誌]

Although gene polymorphisms in the renin-angiotensin system (RAS) are predisposing factors for cardiovascular diseases, the precise mechanisms and interactions among confounding factors have not been clarified. We investigated whether genetic variants of RAS are involved in insulin sensitivity in a Japanese general population. During a medical checkup in 2001, participants (n=550) were recruited from among the residents of the towns of Tanno and Sobetsu, and written informed consent was obtained to participate in the genetic analysis and the epidemiological study. The insertion/deletion (lID) polymorphism of the angiotensin-converting enzyme gene (ACE), the Met235Thr polymorphism of the angiotensinogen gene (AGT), and the A1166C polymorphism of the angiotensin II type 1 receptor gene (AGTR1) were determined by gel electrophoresis or the TaqMan PCR method. We assessed insulin sensitivity using the homeostasis model assessment insulin resistance (HOMA-IR). The RAS gene polymorphisms were not associated with log-transformed values of HOMA-IR, whereas borderline association (p=0.02) was found between the A1166C polymorphism and dichotomous categorization of insulin resistance (defined as HOMA-IR > or =1.73). Our results suggested that the A1166C polymorphism of AGTR1 might affect insulin resistance by altering the responsiveness to angiotensin II signaling, though this mechanism is as yet inconclusive. Further study is required to confirm these findings in a larger, multi-ethnic population.

Relationship between hepatocellular carcinoma and impaired glucose tolerance among Japanese

M. M.H. Khan, Shigeyuki Saito, Satoru Takagi, Hirofumi Ohnishi, Hisako Izumi, Fumio Sakauchi, Masakazu Washio, Tomoko Sonoda, Yoshie Nagata, Sumiyo Asakura, Kota Kobayashi, Mitsuru Mori, Kazuaki Shimamoto

Hepato-Gastroenterology 53 ( 71 ) 742 - 746 2006年09月 [査読有り]

Background/Aims: Both the incidence of diabetes mellitus (DM) and mortality from Hepatoceuular carcinoma (HCC) are increasing in Japan. As the association of overall cancer and HCC with impaired glucose tolerance (IGT) has been studied rarely in the world including Japan, this study assessed their associations using cohort data of Hokkaido, Japan. Methodology: After getting ethical consent, this study included 908 men and 1,081 women aged 30-77 years during 1977-78 and collected detailed information using the baseline survey. The subjects were followed until 2002 and deaths were recorded using ICD-9. Classifying them into three groups of diabetes status namely DM, IGT, and normal, the relative risk (RR) of mortality was estimated by diabetes status using multivariate Cox model. Results: This study revealed no association between overall cancer and diabetes status. However, the RR of mortality from HCC was about 11 times (HR=10.8,95%CI: 1.3-92.5) higher in IGT compared with normal group. DM group also showed higher risk of mortality than normal group. Conclusions: HCC mortality was significantly high among IGT group. However, as the results of the study were based on small data, further studies with large cohort are needed to address the association of IGT with overall cancer and HCC mortality in Japan. © H.G.E. Update Medical Publishing S.A.

Chronic kidney disease is a risk factor for cardiovascular death in a community-based population in Japan NIPPON DATA90

Koshi Nakamura, Tomonori Okamura, Takehito Hayakawa, Takashi Kadowaki, Yoshikuni Kita, Hirofumi Ohnishi, Shigeyuki Saitoh, Kiyomi Sakata, Akira Okayama, Hirotsugu Ueshima

CIRCULATION JOURNAL ( JAPANESE CIRCULATION SOCIETY ) 70 ( 8 ) 954 - 959 2006年08月 [査読有り]

Background Chronic kidney disease (CKD) has been identified as a risk factor for cardiovascular disease (CVD). Methods and Results The risk of cardiovascular death was evaluated in a large cohort of participants selected randomly from the overall Japanese population. Participants (mean age, 52.4 years) free of previous CVD were followed up for 10 years. Glomerular filtration rate (GFR) was estimated using the abbreviated equation developed at the Cleveland Clinic laboratory for the Modification of Diet in Renal Disease study. Of the 7,316 participants, 6.7% had CKD with a GFR < 60 at baseline. Even after adjustment for other risk factors, the presence of CKD conferred an increased risk of cardiovascular death with a hazard ratio of 1.20 (95% confidence interval, 0.82-1.76). Furthermore, a negative, graded correlation between GFR and risk of cardiovascular death was observed: 1.09 (0.72-1.64) for a 60 <= GFR < 90, 1.15 (0.67-1.99) for a 45 <= GFR < 60, 1.23 (0.49-3.09) for a 30 <= GFR < 45, 5.52 (1.62-18.75) for a 15 <= GFR < 30, 9.12 (2.12-39.29) for a GFR < 15, as compared with normal kidney function (GFR 90). The proportion of excess cardiovascular death due to CKD was 1.3%. Conclusion CKD was an independent risk factor for cardiovascular death in a community-dwelling Japanese population.

Incidence of type 2 diabetes in individuals with central obesity in a rural Japanese population - The Tanno and Sobetsu Study

H Ohnishi, S Saitoh, S Takagi, N Katoh, Y Chiba, H Akasaka, Y Nakamura, K Shimamoto

DIABETES CARE ( AMER DIABETES ASSOC ) 29 ( 5 ) 1128 - 1129 2006年05月 [査読有り]

Incidence of type 2 diabetes in individuals with central obesity in a rural japanese population: The Tanno and Sobetssu study: Response to Oda [13]

Hirofumi Ohnishi, Shigeyuki Saitohi, Satoru Takagii, Nobuo Katohi, Yu Chibai, Hiroshi Akasakai, Yosuke Nakamurai, Kazuaki Shimamotoi

Diabetes Care ( 8 ) 29 ( 8 ) 1989 2006年 [査読有り]

Metabolic syndrome and cardiac disease in Japanese men: Applicability of the concept of metabolic syndrome defined by the National Cholesterol Education Program-Adult Treatment panel III to Japanese men - The Tanno and Sobetsu study

H Takeuchi, S Saitoh, S Takagi, H Ohnishi, J Ohhata, T Isobe, K Shimamoto

HYPERTENSION RESEARCH ( JAPANESE SOC HYPERTENSION CENT ACADEMIC SOC, PUBL OFFICE ) 28 ( 3 ) 203 - 208 2005年03月 [査読有り]

Results of a 6-year follow-up study were used to determine whether the concept of and the criteria for metabolic syndrome as defined by the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) can be applied to Japanese men for prediction of the occurrence of cardiac disease. The subjects were 808 men who underwent mass health check-ups in 1993 and who were not on medication for hypertension, diabetes or hyperlipidemia. Individuals who had hypertriglyceridemia, hypo-high density lipoprotein (HDL) cholesterolemia, high blood pressure, and/or high fasting plasma glucose levels were identified on the basis of the NCEP-ATP III criteria. Not in conformity with the NCEP-ATP III, however, a cut-off value of 85 cm was used for waist girth as an indicator of abdominal obesity. The subjects who had 3 or more risk factors were judged as having metabolic syndrome. The proportion of subjects having metabolic syndrome was 25.3%. In the 6-year follow-up study, cardiac disease occurred in 11.7% of the subjects in the metabolic syndrome group and in 6.7% of the subjects in the non-metabolic syndrome group. Results of regression analysis using Cox's proportional hazards model showed that subjects in the metabolic syndrome group had a 2.2-times greater risk of developing cardiac disease than did subjects in the non-metabolic syndrome group. The concept of metabolic syndrome as defined in the NCEP-ATP III was therefore considered to be useful for predicting the occurrence of cardiac disease in Japanese men.

Establishment and assessment of wide area medical information network system in Hokkaido

H Akashi, H Tokura, H Ohnishi, K Nishikage, T Yamaguchi, K Saijo, T Shinmi, M Nakamura, M Nakayama, H Tatsumi

WEB AND COMMUNICATION TECHNOLOGIES AND INTERNET -RELATED SOCIAL ISSUES - HSI 2005 ( SPRINGER-VERLAG BERLIN ) 3597 179 - 189 2005年 [査読有り]

To support regional medicine in rural area of Hokkaido, we have tried to establish advanced medical information network system. At first we connected two rural town hospitals with SMU (Sapporo Medical University) and performed medical data transmission via the Internet. We used IPsec and regional Internet exchange (IX) for ensuring security and stability. As a second stage, we established a Metropolitan Area Network (MAN), a gigabit network with a 120 km radius in order to connect three medical schools (Hokkaido University, Asahikawa Medical College and SMU) with 10 hospitals. These experiments were performed with Internet technology such as VoIP (voice over IP), VPN, IPsec. As a third stage, we have coined VGN (Virtual Global Network) a concept, which includes IPv6 Topological Addressing Policy. According to the policy we established the IPv6 network to connect SMU with Obihiro area hospitals and a preschool for disabled children. Here, we described details of these experiments in terms of applications and network technologies.

Prevalence of asymptomatic arteriosclerosis obliterans and its relationship with risk factors in inhabitants of rural communities in Japan: Tanno-Sobetsu study

T Fujiwara, S Saitoh, S Takagi, H Ohnishi, J Ohata, H Takeuchi, T Isobe, Y Chiba, N Katoh, H Akasaka, K Shimamoto

ATHEROSCLEROSIS ( ELSEVIER SCI IRELAND LTD ) 177 ( 1 ) 83 - 88 2004年11月 [査読有り]

Objectives: Since arteriosclerosis obliterance in the legs (ASO) causes deterioration of the prognosis of the elderly, prevention of ASO is important for maintenance of their quality of lives. We studied the prevalences of ASO in rural communities in Japan. Methods and results: We measured the ratio of systolic blood pressure in the leg to that in the arm (ABI) using a new device, Form PWV/ABI, in 1398 subjects of both sexes. Subjects with ABI values below 0.9 were considered to have ASO. The prevalence of ASO was 2.7% in all of the subjects, 1.0% in subjects under the age of 60 years, and 3.4% in subjects aged 65 years or more. Multiple regression analysis showed that ABI was correlated with plasma level of total cholesterol in men. There were no significant differences of the mean age, mean fasting plasma glucose level and percentage of patients who smoked between the ASO group and non-ASO group in each sex. Mean cholesterol level in our subjects is lower than the reported levels in Europeans and Americans. The prevalence of ASO increased with increase in the number of risk factors in individual subjects. Conclusions: Among the atherosclerotic risk factors, age and total cholesterol seem to be more important risk factors of ASO than others. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

[Adiponectin levels and coronary risk factors in the elderly].

Isobe T, Saitoh S, Takagi S, Ohnishi H, Ohhata J, Takeuchi H, Fujiwara T, Higashiura K, Ura N, Shimamoto K

Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics ( 3 ) 41 ( 3 ) 328 - 333 2004年05月 [査読有り]

DOI PubMed CiNii

Pulse wave velocity as an indicator of atherosclerosis in impaired fasting glucose - The Tanno and Sobetsu study

H Ohnishi, S Saitoh, S Takagi, J Ohata, T Isobe, Y Kikuchi, H Takeuchi, K Shimamoto

DIABETES CARE ( AMER DIABETES ASSOC ) 26 ( 2 ) 437 - 440 2003年02月 [査読有り]

OBJECTIVE - Brachial-ankle pulse wave velocity (baPWV), as an indicator of atherosclerosis in impaired fasting glucose (IFG), was studied in 232 subjects randomly selected from inhabitants of two rural communities in Japan. RESEARCH DESIGN AND METHODS - BMI, systolic blood pressure (SBP), fasting blood glucose (FBS), lipid parameters, ankle brachial pressure index (ABI), and baPWV were measured in each subject. ABI and baPWV were measured using the recently developed device, form ABI/PWV. The subjects were divided into three groups according FBS level: a normal group consisting of subjects with FBS <110 mg/dl, an IFG group consisting of subjects with FBS 110-125 mg/dl, and a diabetic group consisting of subjects with FBS greater than or equal to126 mg/dl and subjects taking hypoglycemic agents. The parameters in the three groups were compared. RESULTS - it was found that the baPWV value increased with increasing plasma glucose level. Significant differences were found between the baPWV values in the normal and IFG groups (1,518 vs. 1,673 cm/s, P = 0.01) and in the normal and diabetic groups (1,518 vs. 1,771 cm/s, P < 0,0001). The results of multiple regression analysis showed that FBS was closely related to baPWV as well as to age and SBP. CONCLUSIONS - The relationship between IFG and atherosclerosis remains controversial. Further studies are needed to evaluate whether strict control of blood glucose level in patients with IFG will result in the prevention of atherosclerosis progression.

Relation of hypertension and glucose tolerance impairment in elderly people to the development of arteriosclerosis-investigation using pulse wave velocity

Takeshi Isobe, Shigeyuki Saitoh, Satoru Takagi, Hirofumi Ohnishi, Junichi Ohhata, Hiroshi Takeuti, Tadashi Fujiwara, Hirosi Akasaka, Kazuaki Shimamoto

Japanese Journal of Geriatrics ( 6 ) 40 ( 6 ) 610 - 614 2003年 [査読有り]

Hypertension and diabetes are risk factors for arteriosclerosis and have a synergistic effect on the progression of arteriosclerosis. The aim of this study was to determine the correlation between complications of hypertension and diabetes and arteriosclerosis as assessed by pulse wave velocity (PWV) in elderly subjects. The subjects of this study were 186 people aged 60 years or older (mean age: 68.8 ± 5.8 years) who were scheduled to undergo health examinations. PWV, systolic blood pressure (SBP), diastolic blood pressure (DBP), body mass index (BMI), fasting blood sugar (FBS), total cholesterol (TC), triglyceride (TG) and HDL cholesterol (HDL) were measured in each subject. The patients were divided according to the American Diabetes Association (ADA) diagnostic criteria for diabetes based on fasting blood sugar level into the following three groups: a normal (NGT) group (FBS< 110mg/dl), an impaired fasting glucose (IFG) group (110≤FBS< 126mg/dl) and a diabetes mellitus (DM) group (FBS≥126mg/dl or receiving treatment for diabetes). Based on the JNC-VI and WHO/ISH diagnostic criteria, subjects who had a SBP of 140mmHg or higher or a DBP of 90mmHg or higher or who had been taking hypotensive drugs were assigned to the hypertension (HT) group, and the other subjects were assigned to the normotenskm (NT) group. PWV showed significant positive correlations with SBP and FBS (r = 0.499 and r = 0.300, respectively). The effects of hypertension on PWV were significantly higher in subjects with HT than in subjects with NT in all of the glucose tolerance groups (all p< 0.01). Moreover, in the subjects with HT, PWV started to increase from the IFG stage, and PWV was significantly higher in the DM groups than in the NGT group (p< 0.01). In multiple regression analysis using PWV as an objective variable, SBP and FBS were selected as significant explanatory variables. The results of this study indicate the need for stricter management of elderly people with slight glucose tolerance impairment and hypertension in order to prevent the occurrence of arteriosclerosis.

Relationship between insulin-resistance and remnant-like particle cholesterol

H Ohnishi, S Saitoh, S Takagi, J Ohata, T Isobe, Y Kikuchi, H Takeuchi, K Shimamoto

ATHEROSCLEROSIS ( ELSEVIER SCI IRELAND LTD ) 164 ( 1 ) 167 - 170 2002年09月 [査読有り]

We investigated the relationship between insulin-resistance (IR) and remnant-like particle cholesterol (RLP-C) using 472 subjects (174 men and 298 women) randomly selected from inhabitants of two rural communities in Japan, Tanno and Sobetsu. The level of fasting immunoreactive insulin (FIRI), fasting blood glucose (FBS), total cholesterol (TC), triglyceride (TG), HDL cholesterol, LDL cholesterol, and RLP-C were measured in each subject. Homeostasis model assessment (HOMA-R) was used as an indicator of IR. The subjects were divided into two groups according to the value of HOMA-R: an IR group of subjects with HOMA-R greater than or equal to 1.73 and a normal (NR) group of subjects with HOMA-R < 1.73. There was a significant positive correlation between HOMA-R and RLP-C. The value of RLP-C was higher in the IR group than in the NR group (7.1 vs. 3.9 mg/dl in men and 5.3 vs. 3.6 mg/dl in women). The frequency of hyper RLP cholesterolemia (RLP-C &GE; 7.5 mg/dl) was higher in the IR than in the NR group (23.7 vs. 6.6% in men and 20.3 vs. 6.6% in women). The results of multiple regression analysis showed that HOMA-R was closely related to RLP-C. The results of this study suggest that RLP-C is closely associated with IR syndrome. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Detection of cardiac calcinosis in hemodialysis patients by whole-body scintigraphy with 99m-technetium methylene diphosphonate

Mariko Eguchi, Kazufumi Tsuchihashi, Hideki Takizawa, Narifumi Nakahara, Makoto Hagiwara, Hirofumi Ohnishi, Taka-Aki Torii, Akiyoshi Hashimoto, Shigeru Marusaki, Tomoaki Nakata, Nobuyuki Ura, Kazuaki Shimamoto

American Journal of Nephrology ( S. Karger AG ) 20 ( 4 ) 278 - 282 2000年 [査読有り]

A noninvasive method for the diagnosis of cardiac calcinosis, a life- threatening complication in hemodialysis patients with end-stage renal disease (ESRD), has not, as yet, been firmly established. We tested whether whole body scanning with 99m-technetium methylene diphosphonate (MDP) might visualize cardiac calcinosis. In 19 consecutive chronic hemodialysis ESRD patients (13 males and 6 females, aged 40-81, mean 63 ± 8 years) with cardiovascular disease [mitral annular calcinosis and/or calcified aortic valve (n = 4), hemodialysis cardiomyopathy (n = 1), coronary artery disease (n = 9) and peripheral artery atherosclerotic disease (n = 6)], MDP uptake in the heart was compared to that in 7 non-ESRD controls with hyperparathyroidism due to adenoma. Cardiac and lung field MDP uptake was confirmed in only 3 (16%) and 5 (26%) of the 19 ESRD subjects, respectively, but was absent in controls. Positive cardiac uptake was related to cardiac calcified complications (mobile intracardiac calcinosis, myocardial calcinosis and mitral annular calcification) and the duration of hemodialysis (p = 0.015). While it was statistically insignificant, subjects showing MDP uptake were elder and had higher serum Ca or Ca x P product and lower intact parathyroid hormone levels. These results suggest that cardiac calcinosis in ESRD patients can be detected noninvasively by myocardial scintigraphy with 99m-technetium MDP. Copyright (C) 2000 S. Karger AG, Basel.

A Review of Cohort Studies on the Association Between History of Diabetes Mellitus and Occurrence of Cancer.

Mori M, Saitoh S, Takagi S, Obara F, Ohnishi H, Akasaka H, Izumi H, Sakauchi F, Sonoda T, Nagata Y, Shimamoto K

Asian Pacific journal of cancer prevention : APJCP ( 4 ) 1 269 - 276 2000年 [査読有り]

　前のページ - 次のページ　

1

このページの先頭へ▲