2012年08月, XXVIth International Biometric Conference (IBC 2012), Poster Prize; Second Prize　　　　　　　　　　　　　　　
Comparison of risk assessment approaches for adverse drug reactions in the post-marketing study

2011年07月, SASユーザー総会 2011, 最優秀賞　　　　　　　　　　　　　　　
マイクロアレイデータによる予後予測モデル構築における.632+推定量によるエラー率の補正とROC曲線解析

2004年09月, 日本計量生物学会, 奨励賞　　　　　　　　　　　　　　　

Association of Blood Glucose Data With Physiological and Nutritional Data From Dietary Surveys and Wearable Devices: Database Analysis
Takashi Miyakoshi, Yoichi M Ito
JMIR Diabetes, 9, e62831, e62831, JMIR Publications Inc., 2024年12月03日
研究論文（学術雑誌）, Background

Wearable devices can simultaneously collect data on multiple items in real time and are used for disease detection, prediction, diagnosis, and treatment decision-making. Several factors, such as diet and exercise, influence blood glucose levels; however, the relationship between blood glucose and these factors has yet to be evaluated in real practice.

Objective

This study aims to investigate the association of blood glucose data with various physiological index and nutritional values using wearable devices and dietary survey data from PhysioNet, a public database.

Methods

Three analytical methods were used. First, the correlation of each physiological index was calculated and examined to determine whether their mean values or SDs affected the mean value or SD of blood glucose. To investigate the impact of each physiological indicator on blood glucose before and after the time of collection of blood glucose data, lag data were collected, and the correlation coefficient between blood glucose and each physiological indicator was calculated for each physiological index. Second, to examine the relationship between postprandial blood glucose rise and fall and physiological and dietary nutritional assessment indices, multiple regression analysis was performed on the relationship between the slope before and after the peak in postprandial glucose over time and physiological and dietary nutritional indices. Finally, as a supplementary analysis to the multiple regression analysis, a 1-way ANOVA was performed to compare the relationship between the upward and downward slopes of blood glucose and the groups above and below the median for each indicator.

Results

The analysis revealed several indicators of interest: First, the correlation analysis of blood glucose and physiological indices indicated meaningful relationships: acceleration SD (r=–0.190 for lag data at –15-minute values), heart rate SD (r=–0.121 for lag data at –15-minute values), skin temperature SD (r=–0.121), and electrodermal activity SD (r=–0.237) for lag data at –15-minute values. Second, in multiple regression analysis, physiological indices (temperature mean: t=2.52, P=.01; acceleration SD: t=–2.06, P=.04; heart rate_30 SD: t=–2.12, P=.04; electrodermal activity_90 SD: t=1.97, P=.049) and nutritional indices (mean carbohydrate: t=6.53, P<.001; mean dietary fiber: t=–2.51, P=.01; mean sugar: t=–3.72, P<.001) were significant predictors. Finally, the results of the 1-way ANOVA corroborated the findings from the multiple regression analysis.

Conclusions

Similar results were obtained from the 3 analyses, consistent with previous findings, and the relationship between blood glucose, diet, and physiological indices in the real world was examined. Data sharing facilitates the accessibility of wearable data and enables statistical analyses from various angles. This type of research is expected to be more common in the future.

Assessment of factors associated with antipsychotic-induced weight gain: A nationwide cohort study
Shuhei Ishikawa, Naoki Hashimoto, Ryo Okubo, Ryo Sawagashira, Ryodai Yamamura, Yoichi M. Ito, Norihiro Sato, Ichiro Kusumi
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 111231, 111231, Elsevier BV, 2024年12月
研究論文（学術雑誌）

A nomogram to predict skin barrier dysfunction induced by mechanical irritation during skincare in hospitalized Japanese older adults
Issei Konya, Rika Yano, Yoichi M. Ito, Hiroaki Iwata, Mayumi Yoshida, Chiaki Watanabe, Akemi Morita
Geriatric Nursing, Elsevier BV, 2024年11月
研究論文（学術雑誌）

Decision regret after curative treatment and its association with the decision-making process and quality of life for prostate cancer patients.
Miho Sato, Takahiro Osawa, Kentaro Nishioka, Tomohiko Miyazaki, Shuhei Takahashi, Takashi Mori, Takayuki Hashimoto, Haruka Miyata, Ryuji Matsumoto, Takashige Abe, Kazuki Ohashi, Sachiyo Murai, Yoichi M Ito, Nobuo Shinohara
International journal of urology : official journal of the Japanese Urological Association, 2024年10月09日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: To determine how the treatment decision-making process and posttreatment health-related quality of life (HRQOL) are related to regret about treatment choice for prostate cancer patients in Japan. METHODS: We invited a total of 614 patients who were treated with radiation therapy (RT), radical prostatectomy (RP), or active surveillance/watchful waiting (AS/WW) from April 2007 to March 2021. Posttreatment regret was evaluated by the Decision Regret Scale. HRQOL was evaluated by the Expanded Prostate Cancer Index Composite and the 12-item Short Form Survey. The decision-making process was assessed by patient evaluation of the decision-making process. We compared the decision regret scale scores across treatment types, HRQOL, and decision-making processes. RESULTS: Data from 371 patients were analyzed (RT: 202, RP: 149, AS/WW: 20). The median length of time since treatment was 64 (IQR: 43-93) months. The decision regret scale scores were not significantly different among the treatment groups but were significantly greater (strong regret) in patients with poor urinary summary scores, bowel summary scores, and hormonal summary scores. The decision regret scale scores were significantly lower (less regret) for patients who reported being adequately informed at the time of the treatment decision and who had adequately communicated their questions and concerns to physicians than for patients who reported less adequate communication. This result was also observed among patients who reported low HRQOL scores. CONCLUSIONS: These findings underline the important influence of posttreatment HRQOL and decision-making as an interactive process between physicians and their patients on posttreatment regret in prostate cancer patients.

Investigation of interfractional range variation owing to anatomical changes with beam directions based on water equivalent thickness in proton therapy for pancreatic cancer.
Yuhei Kikkawa, Hideaki Ueda, Yusuke Uchinami, Norio Katoh, Hidefumi Aoyama, Yoichi M Ito, Kohei Yokokawa, Ye Chen, Taeko Matsuura, Naoki Miyamoto, Seishin Takao
Journal of radiation research, 2024年10月08日, ［国際誌］
英語, 研究論文（学術雑誌）, To assess the interfractional anatomical range variations (ARVs) with beam directions and their impact on dose distribution in intensity modulated proton therapy, we analyzed water equivalent thickness (WET) from 10 patients with pancreatic cancer. The distributions of the interfractional WET difference ($\Delta{\mathrm{WET } }^{\theta }$) across 360° were visualized using polar histograms. Interfractional ARVs were evaluated using the mean absolute error and ΔWET pass rate, indicating the percentage of $\Delta \mathrm{WE},{\mathrm{T } }^{\theta }$ < thresholds. The impact on dose distribution in proton therapy was evaluated based on two treatment plans for 40 Gy(RBE)/5 fractions: 'Plan A', using two beam angles, in which the target was closest to the body surface among four perpendicular directions; and 'Plan B', using two beam angles with small ARVs. Analysis revealed individual variations in angular trends of interfractional ARVs. Three distinct trends were identified: Group 1 exhibited small ARVs around posterior directions; Group 2 exhibited small ARVs except ~60°; Group 3 demonstrated minimal ARVs only ~90°. In dose evaluation, while 150° and 210° were selected in Plan B for 9 out of 10 patients, for the remaining patient, 60° and 90° were chosen. Comparing dose volume histogram parameters for all patients, Plan B significantly reduced target coverage loss while maintaining organ-at-risk sparing comparable to Plan A. These results demonstrated that selecting beam angles with small interfractional ARVs for each patient enhances the robustness of dose distribution, reducing target coverage loss.

Intravenous infusion of auto-serum-expanded autologous mesenchymal stem cells into chronic severe brain injury patients
Tomohiro Yamaki, Shinichi Oka, Satoshi Iyama, Masanori Sasaki, Rie Onodera, Yuko Kataoka-Sasaki, Takahiro Namioka, Ai Namioka, Masahito Nakazaki, Mitsuhiro Takemura, Ryo Ukai, Takahiro Yokoyama, Yuichi Sasaki, Tatsuro Yamashita, Masato Kobayashi, Misako Yamaguchi, Marina Fukino, Taro Takazawa, Megumi Hayasaka, Takamitsu Owaku, Mika Funakura, Shinji Onodera, Yoichi M. Ito, Masayoshi Kobune, Junji Kato, Sumio Ishiai, Jeffery D. Kocsis, Masaru Odaki, Yasuo Iwadate, Shigeki Kobayashi, Osamu Honmou
Interdisciplinary Neurosurgery: Advanced Techniques and Case Management, 36, 2024年06月
研究論文（学術雑誌）, Objective: This study explores safety, feasibility, and potential improvement in functional status after intravenous infusion of mesenchymal stem cells (MSCs) in chronic severe brain injury (BI) patients. Methods: An intravenous infusion of autologous MSCs in autoserum cultured under Good Manufacturing Practice was delivered to four chronic patients with BI. In addition to assessing feasibility and safety, neurological function was evaluated using the National Institutes of Health Stroke Scale, Fugl-Meyer Assessment, Barthel Index, and cognitive-related behavioral assessment. Imaging studies with 18F-FDG-PETCT and 11C-methionine-PETCT (METPET) were carried out to evaluate brain metabolic activity. Results: No serious adverse events were recorded. None of the patients developed CNS tumors, abnormal cell growth, or neurological deterioration. While this initial case series was not blinded, gradual functional improvement was observed after MSC infusion. Serial 11C-METPETs displayed a statistically significant increase in methionine uptake, primarily in the thalamus and pons. Conclusion: We emphasize that this study was unblinded and did not exclude placebo effects, the contribution of endogenous recovery, or observer bias; however, our observations support feasibility and safety. No adverse events were observed. The data suggests improved quality of life after infused MSCs; however, a blinded, larger-scale study will be necessary to fully address this possibility.

Cerebral oxygenation saturation in childhood: difference by age and comparison of two cerebral oximetry algorithms.
Yasunori Kubo, Yusuke Itosu, Tomonori Kubo, Hitoshi Saito, Kazufumi Okada, Yoichi M Ito, Yuji Morimoto
Journal of clinical monitoring and computing, 38, 3, 639, 648, 2024年06月, ［国際誌］
英語, 研究論文（学術雑誌）, Few reports are available on the monitoring of regional cerebral oxygen saturation (rSO2) in pediatric patients undergoing non-cardiac surgical procedures. In addition, no study has examined the rSO2 levels in children of a broad age range. In this study, we aimed to assess and compare rSO2 levels in pediatric patients of different age groups undergoing non-cardiac surgery. We used two oximeters, tNIRS-1, which uses time-resolved spectroscopy, and conventional INVOS 5100C. Seventy-eight children-26 infants, 26 toddlers, and 26 schoolchildren-undergoing non-cardiac surgery were included. We investigated the differences in the rSO2 levels among the age groups and the correlation between the models and physiological factors influencing the rSO2 values. rSO2 measured by INVOS 5100C was significantly lower in infants than those in other patients. rSO2 measured by tNIRS-1 was higher in the toddler group than those in the other groups. The rSO2 values of tNIRS-1 and INVOS 5100C were moderately correlated (r = 0.41); however, those of INVOS 5100C were approximately 20% higher, and a ceiling effect was observed. The values in INVOS 5100C and tNIRS-1 were affected by blood pressure and the minimum alveolar concentration of sevoflurane, respectively. In pediatric patients undergoing non-cardiac surgery, rSO2 values differed across the three age groups, and the pattern of these differences varied between the two oximeters employing different algorithms. Further research must be conducted to clarify cerebral oxygenation in children.

A Single-Institution Prospective Study To Evaluate the Safety and Efficacy of Real- Time Image-Gated Spot-Scanning Proton Therapy (RGPT) for Prostate Cancer.
Kentaro Nishioka, Takayuki Hashimoto, Takashi Mori, Yusuke Uchinami, Rumiko Kinoshita, Norio Katoh, Hiroshi Taguchi, Koichi Yasuda, Yoichi M Ito, Seishin Takao, Masaya Tamura, Taeko Matsuura, Shinichi Shimizu, Hiroki Shirato, Hidefumi Aoyama
Advances in radiation oncology, 9, 5, 101464, 101464, 2024年05月, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: In real-time image-gated spot-scanning proton therapy (RGPT), the dose distribution is distorted by gold fiducial markers placed in the prostate. Distortion can be suppressed by using small markers and more than 2 fields, but additional fields may increase the dose to organs at risk. Therefore, we conducted a prospective study to evaluate the safety and short-term clinical outcome of RGPT for prostate cancer. METHODS AND MATERIALS: Based on the previously reported frequency of early adverse events (AE) and the noninferiority margin of 10%, the required number of cases was calculated to be 43 using the one-sample binomial test by the Southwest Oncology Group statistical tools with the one-sided significance level of 2.5% and the power 80%. Patients with localized prostate cancer were enrolled and 3 to 4 pure gold fiducial markers of 1.5-mm diameter were inserted in the prostate. The prescribed dose was 70 Gy(relative biologic effectiveness) in 30 fractions, and treatment was performed with 3 fields from the left, right, and the back, or 4 fields from either side of slightly anterior and posterior oblique fields. The primary endpoint was the frequency of early AE (≥grade 2) and the secondary endpoint was the biochemical relapse-free survival rate and the frequency of late AE. RESULTS: Forty-five cases were enrolled between 2015 and 2017, and all patients completed the treatment protocol. The median follow-up period was 63.0 months. The frequency of early AE (≥grade 2) was observed in 4 cases (8.9%), therefore the noninferiority was verified. The overall 5-year biochemical relapse-free survival rate was 88.9%. As late AE, grade 2 rectal bleeding was observed in 8 cases (17.8%). CONCLUSIONS: The RGPT for prostate cancer with 1.5-mm markers and 3- or 4- fields was as safe as conventional proton therapy in early AE, and its efficacy was comparable with previous studies.

Influence of epicardial adipose tissue inflammation and adipocyte size on postoperative atrial fibrillation in patients after cardiovascular surgery
Hiroyuki Natsui, Masaya Watanabe, Takashi Yokota, Satonori Tsuneta, Yoshizuki Fumoto, Haruka Handa, Matsushima Shouji, Jiro Koya, Kotaro Nishino, Daishiro Tatsuta, Takuya Koizumi, Takahide Kadosaka, Motoki Nakao, Taro Koya, Taro Temma, Yoichi M. Ito, Hatanaka C. Kanako, Yutaka Hatanaka, Shingu Yasushige, Satoru Wakasa, Shuhei Miura, Takahiko Masuda, Naritomo Nishioka, Shuichi Naraoka, Kayoko Ochi, Tomoko Kudo, Tsugumine Ishikawa, Toshihisa Anzai
Physiological Reports, 12, 6, Wiley, 2024年03月28日, ［査読有り］
英語, 研究論文（学術雑誌）, Abstract

Epicardial adipose tissue (EAT) is an active endocrine organ that is closely associated with occurrence of atrial fibrillation (AF). However, the role of EAT in the development of postoperative AF (POAF) remains unclear. We aimed to investigate the association between EAT profile and POAF occurrence in patients who underwent cardiovascular surgery. We obtained EAT samples from 53 patients to evaluate gene expression, histological changes, mitochondrial oxidative phosphorylation (OXPHOS) capacity in the EAT, and protein secretion in EAT‐conditioned medium. EAT volume was measured using computed tomography scan. Eighteen patients (34%) experienced POAF within 7 days after surgery. Although no significant difference was observed in EAT profile between patients with and without POAF, logistic regression analysis identified that the mRNA expression levels of tumor necrosis factor‐alpha (TNF‐α) were positively correlated and adipocyte size in the EAT was inversely correlated with onset of POAF, respectively. Mitochondrial OXPHOS capacity in the EAT was not associated with POAF occurrence; however, it showed an inverse correlation with adipocyte size and a positive correlation with adiponectin secretion. In conclusion, changes in the secretory profile and adipocyte morphology of the EAT, which represent qualitative aspects of the adipose tissue, were present before the onset of AF.

Cross-sectional and longitudinal analyses of urinary extracellular vesicle mRNA markers in urothelial bladder cancer patients.
Taku Murakami, Keita Minami, Toru Harabayashi, Satoru Maruyama, Norikata Takada, Akira Kashiwagi, Haruka Miyata, Yasuyuki Sato, Ryuji Matsumoto, Hiroshi Kikuchi, Takashige Abe, Yoichi M Ito, Sachiyo Murai, Nobuo Shinohara, Hiroshi Harada, Takahiro Osawa
Scientific reports, 14, 1, 6801, 6801, 2024年03月21日, ［国際誌］
英語, 研究論文（学術雑誌）, We designed this multi-center prospective study with the following objectives: (1) the cross-sectional validation of extracellular vesicles (EV) mRNA markers to detect urothelial bladder cancer (UBC) before transurethral resection of bladder cancer (TURBT), and (2) the longitudinal validation of EV mRNA markers to monitor non-muscle invasive bladder cancer (NMIBC) recurrence after TURBT. EV mRNA markers evaluated in this study were KRT17, GPRC5A, and SLC2A1 in addition to two additional markers from literatures, MDK and CXCR2, and measured by quantitative RT-PCR with normalization by a reference gene (ALDOB). Diagnostic performances of EV mRNA markers were compared to conventional markers. Regarding the first objective, we confirmed that EV mRNA biomarkers in urine were higher in UBC patients, particularly those with higher stage/grade tumors, than in those without UBC (n = 278 in total) and the diagnostic performance of EV mRNA MDK and KRT17 outperformed conventional biomarkers with AUC 0.760 and 0.730, respectively. Concerning the second objective, we prospectively analyzed the time courses of EV mRNA markers while NMIBC patients (n = 189) (median follow-up 19 months). The expression of EV mRNA KRT17 was significantly high in patients with recurrence, while it gradually decreased over time in those without recurrence (p < 0.01).

Intracerebral transplantation of MRI-trackable autologous bone marrow stromal cells for patients with subacute ischemic stroke.
Masahito Kawabori, Satoshi Kuroda, Hideo Shichinohe, Kaoru Kahata, Souichi Shiratori, Satoshi Ikeda, Taisuke Harada, Kenji Hirata, Khin Khin Tha, Masato Aragaki, Shunsuke Terasaka, Yoichi M Ito, Naoki Nishimoto, Shunsuke Ohnishi, Ichiro Yabe, Kohsuke Kudo, Kiyohiro Houkin, Miki Fujimura
Med (New York, N.Y.), 2024年03月18日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Ischemic stroke is one of the leading causes of death and neurological disability worldwide, and stem cell therapy is highly expected to reverse the sequelae. This phase 1/2, first-in-human study evaluated the safety, feasibility, and monitoring of an intracerebral-transplanted magnetic resonance imaging (MRI)-trackable autologous bone marrow stromal cell (HUNS001-01) for patients with subacute ischemic stroke. METHODS: The study included adults with severe disability due to ischemic stroke. HUNS001-01 cultured with human platelet lysates and labeled with superparamagnetic iron oxide was stereotactically transplanted into the peri-infarct area 47-64 days after ischemic stroke onset (dose: 2 or 5 × 107 cells). Neurological and radiographic evaluations were performed throughout 1 year after cell transplantation. The trial was registered at UMIN Clinical Trial Registry (number UMIN000026130). FINDINGS: All seven patients who met the inclusion criteria successfully achieved cell expansion, underwent intracerebral transplantation, and completed 1 year of follow-up. No product-related adverse events were observed. The median National Institutes of Health Stroke Scale and modified Rankin scale scores before transplantation were 13 and 4, which showed improvements of 1-8 and 0-2, respectively. Cell tracking proved that the engrafted cells migrated toward the infarction border area 1-6 months after transplantation, and the quantitative susceptibility mapping revealed that cell signals at the migrated area constantly increased throughout the follow-up period up to 34% of that of the initial transplanted site. CONCLUSIONS: Intracerebral transplantation of HUNS001-01 was safe and well tolerated. Cell tracking shed light on the therapeutic mechanisms of intracerebral transplantation. FUNDING: This work was supported by the Japan Agency for Medical Research and Development (AMED; JP17bk0104045 and JP20bk0104011).

Development of a simulator and training curriculum for liver trauma surgery training for general surgeons
Hiroyasu Tojima, Soichi Murakami, Saseem Poudel, Yo Kurashima, Toshimichi Asano, Takehiro Noji, Kazufumi Okada, Yoichi M. Ito, Hiroyuki Kaneko, Yoshimitsu Izawa, Hiroshi Homma, Satoshi Hirano
Global Surgical Education - Journal of the Association for Surgical Education, 3, 1, Springer Science and Business Media LLC, 2024年03月17日
研究論文（学術雑誌）

The Evaluation Study for Social Cognition Measures in Japan: Psychometric properties, relationships with social function, and recommendations
Hisashi Akiyama, Ryo Okubo, Atsuhito Toyomaki, Akane Miyazaki, Sachiko Hattori, Mariko Nohara, Yohei Sasaki, Ryotaro Kubota, Hiroki Okano, Kanami Takahashi, Yumi Hasegawa, Izumi Wada, Takashi Uchino, Kazuyoshi Takeda, Satoru Ikezawa, Takahiro Nemoto, Yoichi M Ito, Naoki Hashimoto
Asian Journal of Psychiatry, 104003, 104003, Elsevier BV, 2024年03月
研究論文（学術雑誌）

Eribulin for patients with metastatic extramammary Paget disease: Study protocol for a single-arm phase II trial.
Takuya Maeda, Teruki Yanagi, Keiko Tokuchi, Takeru Funakoshi, Nao Horie, Toshiyuki Isoe, Yoichi M Ito, Norihiro Sato, Hideyuki Ujiie
Experimental dermatology, 33, 1, e14993, 2024年01月, ［国際誌］
英語, 研究論文（学術雑誌）, Extramammary Paget disease (EMPD) is a rare cutaneous malignancy that predominantly affects the anogenital areas of the elderly. Although the efficacy of docetaxel and other cytotoxic agents for advanced EMPD has been reported in small retrospective case studies, no treatment has been proven effective in prospective clinical trials. We established the world's first in vivo EMPD experimental model (a patient-derived xenograft model). In our treatment experiment, xenograft tumours showed a remarkable response to eribulin. This study evaluates the efficacy of eribulin for patients with advanced EMPD. In October 2022, we started a single-arm phase II trial to evaluate the efficacy of eribulin as a treatment for adult patients with unresectable EMPD with measurable lesions. Enrolment in this clinical trial is open to patients with any prior treatment for EMPD. The primary endpoint is overall response rate; the secondary endpoints include disease control rate, overall survival, progression-free survival and adverse events. The study protocol was approved by the Ethics Committee of Hokkaido University and the other collaborating institutions. If the primary endpoint is met, it is our hope that eribulin will be regarded as a standard medication for patients with advanced EMPD.

Risk factors for abnormal glucose metabolism during antipsychotic treatment: A prospective cohort study.
Takashi Miyakoshi, Shuhei Ishikawa, Ryo Okubo, Naoki Hashimoto, Norihiro Sato, Ichiro Kusumi, Yoichi M Ito
Journal of psychiatric research, 168, 149, 156, 2023年10月27日, ［国際誌］
英語, 研究論文（学術雑誌）, Antipsychotic medications increase the risk of abnormal glucose metabolism. However, in clinical practice, it is difficult to predict this risk because it is affected by medication-related and background factors. This study aimed to identify the risk factors for abnormal glucose metabolism during antipsychotic treatment. We conducted a multicenter, prospective, cohort study in patients with schizophrenia, schizoaffective disorder, or bipolar disorder. Of these patients, those with prediabetes or possible diabetes were excluded. Finally, 706 patients were included in the analysis. The hazard ratio (HR) for each factor was calculated for events of progression to hyperglycemia using time-dependent Cox regression analysis stratified according to facility type and adjusted for available background and drug-related factors. Treatments with olanzapine (HR = 2.06, 95% confidence interval [CI] = 1.05-4.05), clozapine (HR = 4.25, 95% CI = 1.56-11.60), and chlorpromazine (HR = 4.48, 95% CI = 1.21-16.57), overweight and obesity (HR = 1.57, 95% CI = 1.02-2.41), and hypertriglyceridemia (HR = 1.72, 95% CI = 1.02-2.88) were associated with a significantly higher occurrence of hyperglycemic progression. The number and daily dose of antipsychotics were not associated with their occurrence. Our study demonstrated that more careful monitoring is necessary during olanzapine, clozapine, and chlorpromazine treatment because of the higher occurrence of abnormalities in glucose metabolism. Furthermore, patients with obesity or hypertriglyceridemia warrant monitoring for the occurrence of abnormal glucose metabolism, regardless of the type of antipsychotic medication.

Inverse association between glucose variability and body fat in type 2 diabetes with impaired endogenous insulin secretion assessed using continuous glucose monitoring: A prospective observational study.
Aika Miya, Akinobu Nakamura, Yuka Suzuki, Hiroshi Nomoto, Hiraku Kameda, Kyu Yong Cho, Yoichi M Ito, So Nagai, Hideaki Miyoshi, Tatsuya Atsumi
Diabetes, obesity & metabolism, 25, 7, 1883, 1889, 2023年07月, ［国際誌］
英語, 研究論文（学術雑誌）, AIM: To evaluate the contribution of body fat mass and serum adiponectin concentration to glucose variability (GV) stability in people with type 2 diabetes with impaired versus preserved endogenous insulin secretion. MATERIALS AND METHODS: This multicentre prospective observational study included 193 people with type 2 diabetes who underwent ambulatory continuous glucose monitoring, abdominal computed tomography and fasting blood sampling. A fasting C-peptide (FCP) concentration >2 ng/mL was defined as preserved endogenous insulin secretion. The participants were divided into high (FCP > 2 ng/mL) and low FCP subgroups (FCP ≤ 2 ng/mL). Multivariate regression analysis was performed in each subgroup. RESULTS: In the high FCP subgroup, the coefficient of variation (CV) in GV was unrelated to abdominal fat area. In the low FCP subgroup, a high CV was significantly related to small abdominal visceral fat area (β = -0.11, standard error 0.03; P < 0.05) and to small subcutaneous fat area (β = -0.09, standard error 0.04; P < 0.05). No significant relationship between serum adiponectin concentration and continuous glucose monitoring-related variables was found. CONCLUSIONS: The contribution of body fat mass to GV depends on the endogenous insulin secretion residue. A small body fat area has independent adverse effects on GV in people with type 2 diabetes and impaired endogenous insulin secretion.

Associations of COVID-19 symptoms with omicron subvariants BA.2 and BA.5, host status, and clinical outcomes in Japan: a registry-based observational study.
Sho Nakakubo, Naoki Kishida, Kenichi Okuda, Keisuke Kamada, Masami Iwama, Masaru Suzuki, Isao Yokota, Yoichi M Ito, Yasuyuki Nasuhara, Richard C Boucher, Satoshi Konno
The Lancet. Infectious diseases, 2023年06月30日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Previous SARS-CoV-2 infection and vaccination, coupled with the rapid evolution of SARS-CoV-2 variants, have modified COVID-19 clinical manifestations. We aimed to characterise the clinical symptoms of COVID-19 individuals in omicron BA.2 and BA.5 Japanese pandemic periods to identify omicron and subvariant associations between symptoms, immune status, and clinical outcomes. METHODS: In this registry-based observational study, individuals registered in Sapporo's web-based COVID-19 information system entered 12 pre-selected symptoms, days since symptom onset, vaccination history, SARS-CoV-2 infection history, and background. Eligibility criteria included symptomatic individuals who tested positive for SARS-CoV-2 (PCR or antigen test), and individuals who were not tested for SARS-CoV-2 but developed new symptoms after a household member tested positive for SARS-CoV-2. Symptom prevalence, variables associated with symptoms, and symptoms associated with progression to severe disease were analysed. FINDINGS: Data were collected and analysed between April 25 and Sept 25, 2022. For 157 861 omicron-infected symptomatic individuals, cough was the most common symptom (99 032 [62·7%] patients), followed by sore throat (95 838 [60·7%] patients), nasal discharge (69 968 [44·3%] patients), and fever (61 218 [38·8%] patients). Omicron BA.5 infection was associated with a higher prevalence of systemic symptoms than BA.2 in vaccinated and unvaccinated individuals (adjusted odds ratio [OR] for fever: 2·18 [95% CI 2·12-2·25]). Omicron breakthrough-infected individuals with three or more vaccinations or previous infection were less likely to exhibit systemic symptoms (fever 0·50 [0·49-0·51]), but more likely to exhibit upper respiratory symptoms (sore throat 1·33 [1·29-1·36]; nasal discharge 1·84 [1·80-1·89]). Infected older individuals (≥65 years) had lower odds for all symptoms. However, when symptoms were manifest, systemic symptoms were associated with increased odds for severe disease (dyspnoea 3·01 [1·84-4·91]; fever 2·93 [1·89-4·52]), whereas upper respiratory symptoms were associated with decreased odds (sore throat 0·38 [0·24-0·63]; nasal discharge 0·48 [0·28-0·81]). INTERPRETATION: Host immunological status, omicron subvariant, and age were associated with a spectrum of COVID-19 symptoms and outcomes. BA.5 produced a higher systemic symptom prevalence than BA.2. Vaccination and previous infection reduced systemic symptom prevalence and improved outcomes but increased upper respiratory tract symptom prevalence. Systemic, but not upper respiratory, symptoms in older people heralded severe disease. Our findings could serve as a practical guide to use COVID-19 symptoms to appropriately modify health-care strategies and predict clinical outcomes for older patients with omicron infections. FUNDING: Japan Agency for Medical Research and Development.

Five-Year Stroke Risk and Its Predictors in Asymptomatic Moyamoya Disease: Asymptomatic Moyamoya Registry (AMORE).
Satoshi Kuroda, Shusuke Yamamoto, Takeshi Funaki, Miki Fujimura, Hiroharu Kataoka, Tomohito Hishikawa, Jun Takahashi, Hidenori Endo, Tadashi Nariai, Toshiaki Osato, Nobuhito Saito, Norihiro Sato, Emiko Hori, Yoichi M Ito, Susumu Miyamoto
Stroke, 54, 6, 1494, 1504, 2023年06月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Long-term outcomes are unknown in patients with asymptomatic moyamoya disease. In this report, we aimed to clarify their 5-year risk of stroke and its predictors. METHODS: We are conducting a multicenter, prospective cohort study (Asymptomatic Moyamoya Registry) in Japan. Participants were eligible if they were 20 to 70 years, had bilateral or unilateral moyamoya disease, experienced no episodes suggestive of TIA and stroke; and were functionally independent (modified Rankin Scale score 0-1). Demographic and radiological information was collected at enrollment. In this study, they are still followed up for 10 years. In this interim analysis, we defined the primary end point as a stroke occurring during a 5-year follow-up period. Independent predictors for stroke were also determined, using a stratification analysis method. RESULTS: Between 2012 and 2015, we enrolled 109 patients, of whom 103 patients with 182 involved hemispheres completed the 5-year follow-up. According to the findings on DSA and MRA, 143 hemispheres were judged as moyamoya disease and 39 hemispheres as questionable manifestations (isolated middle cerebral artery stenosis). The patients with questionable hemispheres were significantly older, more often male, and more frequently had hypertension than those with moyamoya hemisphere. Moyamoya hemispheres developed 7 strokes, including 6 hemorrhagic and 1 ischemic stroke, during the first 5 years. The annual risk of stroke was 1.4% per person, 0.8% per hemisphere, and 1.0% per moyamoya hemisphere. Independent predictor for stroke was Grade-2 choroidal anastomosis (hazard ratio, 5.05 [95% CI, 1.24-20.6]; P=0.023). Furthermore, microbleeds (hazard ratio, 4.89 [95% CI, 1.13-21.3]; P=0.0342) and Grade-2 choroidal anastomosis (hazard ratio, 7.05 [95% CI, 1.62-30.7]; P=0.0093) significantly predicted hemorrhagic stroke. No questionable hemispheres developed any stroke. CONCLUSIONS: The hemispheres with asymptomatic moyamoya disease may carry a 1.0% annual risk of stroke during the first 5 years, the majority of which are hemorrhagic stroke. Grade-2 choroidal anastomosis may predict stroke, and the microbleeds and Grade-2 choroidal anastomosis may carry the risk for hemorrhagic stroke. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: UMIN000006640.

Proton beam therapy for gliomas: a multicenter prospective registry study from all proton beam facilities in Japan
Takashi Mori, Masashi Mizumoto, Katsuya Maebayashi, Kentaro Nishioka, Yoshiki Arakawa, Kazuhiko Kurozumi, Koichi Yasuda, Taisuke Sumiya, Hiroyasu Tamamura, Yoshitaka Sato, Takahiro Waki, Masaru Takagi, Yu Takada, Tomoaki Okimoto, Masao Murakami, Yasuhiro Kikuchi, Kazufumi Okada, Yoichi M Ito, Tetsuo Akimoto, Hidefumi Aoyama
Journal of Radiation Research, Oxford University Press (OUP), 2023年04月07日
研究論文（学術雑誌）, Abstract

We reviewed the outcomes of glioma patients enrolled in a prospective observational registry study of proton beam therapy (PBT) in Japan. The inclusion criteria were glioma patients registered in the Electronic Data Capture system, the Proton-net, between May 2016 and July 2019. Data on patient characteristics, treatments, late adverse events, survival status, recurrence and secondary tumors were extracted and statistically analyzed. The primary endpoint was the overall survival (OS) rate, and the secondary endpoints were the progression-free survival (PFS) rate and cumulative local recurrence rate (cLRR). Of the 65 primary brain tumor patients registered, 29 glioma patients from eight of 19 PBT facilities met the inclusion criteria. There were 19 glioblastoma patients, eight of other malignant gliomas, and two of low-grade gliomas. For glioblastomas, with a median follow-up period of 16 months, the median survival time was 21.2 months and the OS at 1, 2, 3 and 4 years were 77.4%, 44.9%, 23.9% and 23.9%, respectively. The median PFS period was 10.1 months, the 1, 2, 3 and 4-year PFS were 32.4%, 19.4%, 9.7% and 9.7%, respectively. The 1, 2, 3 and 4-year cLRR were 56.1%, 68.8%, 78.4 and 78.4%, respectively. Grade 3 brain necrosis was observed in two patients. No secondary tumor was observed. This is the first report on the current status of PBT for gliomas in Japan. For glioblastomas, the outcomes of PBT are estimated to be equivalent to historical data of photon therapy. The results of a prospective comparative evaluation of PBT and photon therapy are awaited.

Development and validation of the Care Transitions Scale for Patients with Heart Failure: A tool for nurses to assess patients' readiness for hospital discharge
Mai Yoshimura, Masumi Kawamura, Satoko Hasegawa, Yoichi M. Ito, Keita Takahashi, Naomi Sumi
Japan Journal of Nursing Science, Wiley, 2023年02月08日
研究論文（学術雑誌）

Associations of COVID-19 Symptoms with Omicron Subvariants BA.2 and BA.5, Host Status, and Clinical Outcomes: A Registry-Based Observational Study in Sapporo, Japan.
Sho Nakakubo, Naoki Kishida, Kenichi Okuda, Keisuke Kamada, Masami Iwama, Masaru Suzuki, Isao Yokota, Yoichi M Ito, Yasuyuki Nasuhara, Richard C Boucher, Satoshi Konno
medRxiv : the preprint server for health sciences, 2023年02月07日, ［国際誌］
英語, BACKGROUND: Previous SARS-CoV-2 infection and vaccination, coupled to rapid evolution of SARS-CoV-2 variants, have modified COVID-19 clinical manifestations. We characterized clinical symptoms of COVID-19 individuals in omicron BA.2 and BA.5 Japanese pandemic periods to identify omicron and subvariant associations between symptoms, immune status, and clinical outcomes. METHODS: Individuals registered in Sapporo's web-based COVID-19 information system entered 12 pre-selected symptoms, days since symptom onset, vaccination history, SARS-CoV-2 infection history, and background. Symptom frequencies, variables associated with symptoms, and symptoms associated with progression to severe disease were analysed. RESULTS: For all omicron-infected individuals, cough was the most common symptom (62.7%), followed by sore throat (60.7%), nasal discharge (44.3%), and fever (38.8%). Omicron BA.5 infection was associated with a higher symptom burden than BA.2 in vaccinated and unvaccinated individuals. Omicron breakthrough-infected individuals with ≥ 3 vaccinations or previous infection were less likely to exhibit systemic symptoms, but more likely to exhibit upper respiratory symptoms. Infected elderly individuals had lower odds for all symptoms, but, when symptoms were manifest, systemic symptoms were associated with an increased risk, whereas upper respiratory symptoms with a decreased risk, of severe disease. CONCLUSION: Host immunological status, omicron subvariant, and age were associated with a spectrum of COVID-19 symptoms and outcomes. BA.5 produced a greater symptom burden than BA.2. Vaccination and prior infection mitigated systemic symptoms and improved outcomes, but increased upper respiratory tract symptom burden. Systemic, but not upper respiratory, symptoms in the elderly heralded severe disease.

Protocol for treating lumbar spinal canal stenosis with a combination of ultrapurified, allogenic bone marrow-derived mesenchymal stem cells and in situ-forming gel: a multicentre, prospective, double-blind randomised controlled trial.
Hideki Sudo, Takashi Miyakoshi, Yudai Watanabe, Yoichi M Ito, Kaoru Kahata, Khin Khin Tha, Nozomi Yokota, Hiroe Kato, Tomoko Terada, Norimasa Iwasaki, Teruyo Arato, Norihiro Sato, Toshiyuki Isoe
BMJ open, 13, 2, e065476, 2023年02月02日, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: In patients with combined lumbar spinal canal stenosis (LSCS), a herniated intervertebral disc (IVD) that compresses the dura mater and nerve roots is surgically treated with discectomy after laminoplasty. However, defects in the IVD after discectomy may lead to inadequate tissue healing and predispose patients to the development of IVD degeneration. Ultrapurified stem cells (rapidly expanding clones (RECs)), combined with an in situ-forming bioresorbable gel (dMD-001), have been developed to fill IVD defects and prevent IVD degeneration after discectomy. We aim to investigate the safety and efficacy of a new treatment method in which a combination of REC and dMD-001 is implanted into the IVD of patients with combined LSCS. METHODS AND ANALYSIS: This is a multicentre, prospective, double-blind randomised controlled trial. Forty-five participants aged 20-75 years diagnosed with combined LSCS will be assessed for eligibility. After performing laminoplasty and discectomy, participants will be randomised 1:1:1 into the combination of REC and dMD-001 (REC-dMD-001) group, the dMD-001 group or the laminoplasty and discectomy alone (control) group. The primary outcomes of the trial will be the safety and effectiveness of the procedure. The effectiveness will be assessed using visual analogue scale scores of back pain and leg pain as well as MRI-based estimations of morphological and compositional quality of the IVD tissue. Secondary outcomes will include self-assessed clinical scores and other MRI-based estimations of compositional quality of the IVD tissue. All evaluations will be performed at baseline and at 1, 4, 12, 24 and 48 weeks after surgery. ETHICS AND DISSEMINATION: This study was approved by the ethics committees of the institutions involved. We plan to conduct dissemination of the outcome data by presenting our data at national and international conferences, as well as through formal publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: jRCT2013210076.

肝細胞癌陽子線治療効果予測におけるADC値指標の検討　　　　　　　　　　　　　　　
藤田 祥博, 加藤 徳雄, 打浪 雄介, 田口 大志, 西岡 健太郎, 森 崇, 安田 耕一, 小泉 富基, 大塚 愛美, 高尾 聖心, 田村 昌也, Sutherland Kenneth, Khin Khin Tha, 伊藤 陽一, 青山 英史
Japanese Journal of Radiology, 41, Suppl., 10, 10, (公社)日本医学放射線学会, 2023年02月
日本語

Change in cerebral circulation during the induction of anesthesia with remimazolam.
Takashi Soejima, Kentaro Ueda, Sakae Hasegawa, Hiromitsu Motoe, Kazufumi Okada, Yoichi M Ito, Koji Hoshino, Yuji Morimoto
Journal of anesthesia, 37, 1, 92, 96, 2023年02月, ［国内誌］
英語, 研究論文（学術雑誌）, PURPOSE: Remimazolam is a new ultra-short-acting benzodiazepine with unknown effects on cerebral circulation. We measured total cerebral hemoglobin concentrations, which reflect cerebral blood volume (CBV), and cerebral oxygen saturation, using time-domain near-infrared spectroscopy, which can measure the absolute values of cerebral hemoglobin concentrations. We also measured cerebral blood flow velocity (CBFV) in the middle cerebral artery using transcranial Doppler as an indicator of cerebral blood flow (CBF). We did so to examine the effect of remimazolam on cerebral circulation in humans, as assessed CBV, CBF, and cerebral oxygen saturation. METHODS: This was a prospective, observational study. Fifteen patients without serious complications scheduled for general anesthesia were recruited. We measured total cerebral hemoglobin concentrations, CBFV, and cerebral oxygen saturation throughout the anesthetic induction course with remimazolam. RESULTS: Total cerebral hemoglobin concentrations did not change during the process (p = 0.51). In contrast, the mean CBFV was reduced by 11% (significant, p = 0.04). The drop in mean blood pressure following the induction of anesthesia was 17%; however, it was within the range of cerebrovascular autoregulation. Moreover, cerebral oxygen saturation increased by 4% (statistically significant, p < 0.01). CONCLUSIONS: We found that anesthetic induction with remimazolam did not alter CBV and reduced CBF in uncomplicated patients.

Distribution of human papilloma virus genotypes and treatment outcomes in definitive radiotherapy for cervical cancer.
Rumiko Kinoshita, Takashi Mitamura, Fumi Kato, Takahiro Hattori, Hajime Higaki, Shuhei Takahashi, Yoshihiro Fujita, Manami Otsuka, Fuki Koizumi, Yusuke Uchinami, Takashi Mori, Kentaro Nishioka, Takayuki Hashimoto, Yoichi M Ito, Hidemichi Watari, Hidefumi Aoyama
Journal of radiation research, 64, 2, 463, 470, 2023年01月03日, ［国際誌］
英語, 研究論文（学術雑誌）, Most oncogenic human papilloma virus (HPV) genotypes stratify into two species, α-7 HPV and α-9 HPV. There are several studies that evaluate the relationship between HPV species and treatment outcomes and reports that HPV species is prognostic. The HPV genotyping was conducted using biopsy specimens which had been stored in these studies. We conducted the study using the HPV test performed by cytology specimens which is less invasive and more useful in clinical settings. This study enrolled 46 patients who received HPV genotyping before the definitive radiotherapy. The results of the HPV genotyping were classified into HPVα-7, HPVα-9 and negatives. Of the 46 patients, 10 were positive for HPVα-7, 21 positive for HPVα-9 and 15 were negative. The median follow-up period was 38 months (range 4-142). The HPVα-7, HPVα-9 and negative groups showed the 3-year overall survival (OS; 59.3%, 80.4% and 72.2% [P = 0.25]); local control (LC; 67.5%, 81% and 80% [P = 0.78]); pelvic control (PC) (50%, 81% and 72.7% [P = 0.032]); pelvic lymph node (PLN) control (78.7%, 95% and 92.3% [P = 0.012]); distant metastasis free (DMF) survival (50%, 75.4% and 42.8% [P = 0.098]); and progression free survival (PFS) rate of patients (30%, 66.7% and 38.9% [P = 0.085]), respectively. Patients with HPVα-7 showed statistically significant poorer PC than the HPVα-9 group, in multivariate analysis. This result is consistent with previous studies for HPV positive patients. The HPV negativity rate was higher in this study than in other studies and further work on this may be needed for clinical use.

Relationships of computed tomography-based small vessel indices of the lungs with ventilation heterogeneity and high transfer coefficients in non-smokers with asthma.
Kaoruko Shimizu, Hirokazu Kimura, Naoya Tanabe, Shotaro Chubachi, Susumu Sato, Masaru Suzuki, Kazuya Tanimura, Hiroaki Iijima, Akira Oguma, Yoichi M Ito, Nobuyasu Wakazono, Michiko Takimoto-Sato, Machiko Matsumoto-Sasaki, Yuki Abe, Nozomu Takei, Hironi Makita, Masaharu Nishimura, Satoshi Konno
Frontiers in physiology, 14, 1137603, 1137603, 2023年, ［国際誌］
英語, 研究論文（学術雑誌）, Background: The mechanism of high transfer coefficients of the lungs for carbon monoxide (Kco) in non-smokers with asthma is explained by the redistribution of blood flow to the area with preserved ventilation, to match the ventilation perfusion. Objectives: To examine whether ventilation heterogeneity, assessed by pulmonary function tests, is associated with computed tomography (CT)-based vascular indices and Kco in patients with asthma. Methods: Participants were enrolled from the Hokkaido-based Investigative Cohort Analysis for Refractory Asthma (Hi-CARAT) study that included a prospective asthmatic cohort. Pulmonary function tests including Kco, using single breath methods; total lung capacity (TLC), using multiple breath methods; and CT, were performed on the same day. The ratio of the lung volume assessed using single breath methods (alveolar volume; VA) to that using multiple breath methods (TLC) was calculated as an index of ventilation heterogeneity. The volume of the pulmonary small vessels <5 mm2 in the whole lung (BV5 volume), and number of BV5 at a theoretical surface area of the lungs from the plural surface (BV5 number) were evaluated using chest CT images. Results: The low VA/TLC group (the lowest quartile) had significantly lower BV5 number, BV5 volume, higher BV5 volume/BV5 number, and higher Kco compared to the high VA/TLC group (the highest quartile) in 117 non-smokers, but not in 67 smokers. Multivariable analysis showed that low VA/TLC was associated with low BV5 number, after adjusting for age, sex, weight, lung volume on CT, and CT emphysema index in non-smokers (not in smokers). Conclusion: Ventilation heterogeneity may be associated with low BV5 number and high Kco in non-smokers (not in smokers). Future studies need to determine the dynamic regional system in ventilation, perfusion, and diffusion in asthma.

Validation of the Japanese version of the Body Image Scale for bladder cancer patients.
Miho Sato, Takahiro Osawa, Takashige Abe, Michitaka Honda, Madoka Higuchi, Shuhei Yamada, Jun Furumido, Hiroshi Kikuchi, Ryuji Matsumoto, Yasuyuki Sato, Yoshihiro Sasaki, Toru Harabayashi, Satoru Maruyama, Norikata Takada, Keita Minami, Hiroshi Tanaka, Ken Morita, Akira Kashiwagi, Sachiyo Murai, Yoichi M Ito, Katsuhiko Ogasawara, Nobuo Shinohara
Scientific reports, 12, 1, 21544, 21544, 2022年12月13日, ［国際誌］
英語, 研究論文（学術雑誌）, The Body Image Scale (BIS) is a 10-item tool that measures the body images of cancer patients. This study aims to validate the Japanese version of the BIS for bladder cancer patients. A multicenter cross-sectional survey was used to identify the participants, which included Japanese bladder cancer patients. The percentage of missing responses, internal consistency, and known-group validity were evaluated. The correlations between the BIS and two HRQOL instruments (the Bladder Cancer Index and the SF-12) were assessed to determine convergent validity. Among 397 patients, 221 patients were treated by transurethral resection of bladder tumor (TURBT) endoscopically, 49 patients underwent cystectomy with neobladder, and 127 patients underwent cystectomy involving stoma. The percentage of missing responses in the BIS ranged from 8.1 to 15.6%. Cronbach's α coefficient was 0.924. Higher BIS scores indicate negative body image, and the median BIS score for patients with native bladders after TURBT (0.5) was significantly lower than those of the patients with neobladder (4.0) and stoma formation (7.0), which indicated the discriminatory ability of the BIS. Each domain of the Bladder Cancer Index and the role summary score of the SF-12 correlated to the BIS scores, which confirmed the convergent validity. A range of BIS scores were identified among patients who reported similar physical summary scores and mental summary scores of the SF-12. This study confirmed the reliability and validity of the Japanese version of the BIS for bladder cancer patients.

Changes in Cerebral Hemodynamics During Systemic Pulmonary Shunt and Pulmonary Artery Banding in Infants with Congenital Heart Disease.
Yoshifumi Takeda, Masataka Yamamoto, Koji Hoshino, Yoichi M Ito, Nobuyasu Kato, Satoru Wakasa, Yuji Morimoto
Pediatric cardiology, 2022年09月01日, ［国際誌］
英語, 研究論文（学術雑誌）, Palliative surgery is often performed in the treatment of congenital heart disease. Two representative palliative procedures are the systemic pulmonary shunt and pulmonary artery banding. Dramatic changes in cerebral hemodynamics may occur in these operations due to changes in the pulmonary-to-systemic blood flow ratio and systemic oxygenation. However, there seem to be almost no studies evaluating them. Accordingly, we evaluated cerebral perfusion by transcranial Doppler ultrasonography and cerebral oxygenation by near infrared spectroscopy during these procedures. In the post hoc analysis of a previous prospective observational study, cerebral blood flow velocities of the middle cerebral artery measured by transcranial Doppler were compared between the start and end of surgery as were the pulsatility index and resistance index. The cerebral oxygenation values were also compared between the start and end of surgery. Twenty-two infants with systemic pulmonary shunt and 20 infants with pulmonary artery banding were evaluated. There were no significant differences of the flow velocities between the start and end of surgery in either procedure. The pulsatility index significantly increased after pulmonary artery banding, which may compete with the increase in cerebral perfusion due to the increase in systemic blood flow. The cerebral oxygenation decreased in both procedures, possibly due to an increase in body temperature. Arterial oxygen saturation was almost the same before and after both procedures. Contrary to our expectation, the changes in cerebral hemodynamics in the palliative operations were small if the management of physiological indices such as arterial oxygen saturation was properly performed during the procedures.

Phase II Study of Ramucirumab Plus Irinotecan Combination Therapy as Second-Line Treatment in Patients with Advanced Gastric Cancer: HGCSG1603.
Yasuyuki Kawamoto, Satoshi Yuki, Kentaro Sawada, Michio Nakamura, Osamu Muto, Susumu Sogabe, Yoshiaki Shindo, Atsushi Ishiguro, Atsushi Sato, Yasushi Tsuji, Masayoshi Dazai, Hiroyuki Okuda, Takashi Meguro, Kazuaki Harada, Mari Sekiguchi, Kazufumi Okada, Yoichi M Ito, Yuh Sakata, Naoya Sakamoto, Yoshito Komatsu
The oncologist, 27, 8, e642-e649, 2022年08月05日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Ramucirumab is a human IgG1 monoclonal vascular endothelial growth factor receptor-2 antibody that inhibits tumor cell growth and affects the tumor cell microenvironment. We assessed the efficacy and safety of ramucirumab plus irinotecan combination therapy as second-line treatment in patients with previously treated advanced gastric cancer. MATERIALS AND METHODS: Patients with advanced gastric cancer refractory or intolerant to primary chemotherapy were included. Ramucirumab 8 mg/kg plus irinotecan 150 mg/m2 combination therapy was administered every 2 weeks. The primary endpoint was progression-free survival rate at 6 months and secondary endpoints were overall survival, progression-free survival, response rate, safety, and dose intensity for each drug. RESULTS: Thirty-five patients were enrolled between January 2018 and September 2019. The progression-free survival rate at 6 months was 26.5% [95%CI, 13.2%-41.8%, P = .1353)]. Median progression-free and overall survivals were 4.2 months (95%CI, 2.5-5.4 months) and 9.6 months (95%CI, 6.4-16.6 months), respectively. The overall response rate was 25.9% (95%CI, 11.1-36.3%) and disease control rate was 85.2% (95%CI, 66.3-95.8%). Grade ≥3 adverse events that occurred in >10% of patients included neutropenia, leucopenia, anemia, anorexia, and febrile neutropenia. No death or new safety signals with a causal relation to the study treatment were observed. CONCLUSION: Although the primary endpoint was not achieved statistically, combination therapy of ramucirumab plus irinotecan showed anticancer activity and a manageable safety profile for second-line treatment of patients with advanced gastric cancer.

Salivary Biomarker Profiles and Chronic Fatigue among Nurses Working Rotation Shifts: An Exploratory Pilot Study
Shinya Yamaguchi, Kazuhiro Watanabe, Naotaka Sugimura, Inaho Shishido, Issei Konya, Tomoko Fujita, Yuichi Yoshimitsu, Shintaro Kato, Yoichi M. Ito, Rika Yano
HEALTHCARE, 10, 8, MDPI, 2022年08月
英語, 研究論文（学術雑誌）, Although nurses' fatigue affects their well-being and patient safety, no effective objective measurements exist. We explored the profiles of salivary biomarkers associated with nurses' chronic fatigue across several shifts. This longitudinal study involved 45 shiftwork nurses and collected their saliva samples before two night and two day shifts for a month. Chronic fatigue was measured using the Cumulative Fatigue Symptom Index before the first night shift. Biomarker profiles were analyzed using hierarchical cluster analysis, and chronic fatigue levels were compared between the profiles. Cortisol profiles were classified into high- and low-level groups across two day shifts; the low-level group presented significantly higher irritability and unwillingness to work. Secretory immunoglobulin A (s-IgA) profiles across the four shifts were classified into high- and low-level groups; the high-level group had significantly higher depressive feelings, decreased vitality, irritability, and unwillingness to work. Cortisol (two day shifts) and s-IgA (four shifts) profiles were combined, and (i) cortisol low-level and s-IgA high-level and (ii) cortisol high-level and s-IgA low-level groups were identified. The former group had significantly higher chronic fatigue sign and irritability than the latter group. The profiles of salivary cortisol and s-IgA across several shifts were associated with nurses' chronic fatigue.

Salivary Biomarker Profiles and Chronic Fatigue among Nurses Working Rotation Shifts: An Exploratory Pilot Study.
Shinya Yamaguchi, Kazuhiro Watanabe, Naotaka Sugimura, Inaho Shishido, Issei Konya, Tomoko Fujita, Yuichi Yoshimitsu, Shintaro Kato, Yoichi M Ito, Rika Yano
Healthcare (Basel, Switzerland), 10, 8, 2022年07月28日, ［国際誌］
英語, 研究論文（学術雑誌）, Although nurses' fatigue affects their well-being and patient safety, no effective objective measurements exist. We explored the profiles of salivary biomarkers associated with nurses' chronic fatigue across several shifts. This longitudinal study involved 45 shiftwork nurses and collected their saliva samples before two night and two day shifts for a month. Chronic fatigue was measured using the Cumulative Fatigue Symptom Index before the first night shift. Biomarker profiles were analyzed using hierarchical cluster analysis, and chronic fatigue levels were compared between the profiles. Cortisol profiles were classified into high- and low-level groups across two day shifts; the low-level group presented significantly higher irritability and unwillingness to work. Secretory immunoglobulin A (s-IgA) profiles across the four shifts were classified into high- and low-level groups; the high-level group had significantly higher depressive feelings, decreased vitality, irritability, and unwillingness to work. Cortisol (two day shifts) and s-IgA (four shifts) profiles were combined, and (i) cortisol low-level and s-IgA high-level and (ii) cortisol high-level and s-IgA low-level groups were identified. The former group had significantly higher chronic fatigue sign and irritability than the latter group. The profiles of salivary cortisol and s-IgA across several shifts were associated with nurses' chronic fatigue.

Intravenous Infusion of Autoserum-Expanded Autologous Mesenchymal Stem Cells in Patients With Chronic Brain Injury: Protocol for a Phase 2 Trial
Shinichi Oka, Tomohiro Yamaki, Masanori Sasaki, Ryo Ukai, Mitsuhiro Takemura, Takahiro Yokoyama, Yuko Kataoka-Sasaki, Rie Onodera, Yoichi M Ito, Shigeki Kobayashi, Jeffery D Kocsis, Yasuo Iwadate, Osamu Honmou
JMIR Research Protocols, 11, 7, e37898, e37898, JMIR Publications Inc., 2022年07月06日
研究論文（学術雑誌）, Background

Brain injuries resulting from motor vehicle accidents and falls, as well as hypoxic insults and other conditions, are one of the leading causes of disability and death in the world. Current treatments are limited but include continuous rehabilitation, especially for chronic brain injury. Recent studies have demonstrated that the intravenous infusion of mesenchymal stem cells (MSCs) has therapeutic efficacy for several neurological diseases, including stroke and spinal cord injury.

Objective

The objective of our investigator-initiated clinical trial is to assess the safety and potential efficacy of the intravenous infusion of autoserum-expanded autologous MSCs for patients with chronic brain injury.

Methods

The (phase 2) trial will be a single-arm, open-label trial with the primary objective of confirming the safety and efficacy of autoserum-expanded autologous MSCs (STR-01; produced under good manufacturing practices) when administered to patients with chronic brain injury. The estimated number of enrolled participants is 6 to 20 patients with a modified Rankin Scale grade of 3 to 5. The assessment of safety and the proportion of cases in which the modified Rankin Scale grade improves by 1 point or more at 180 days after the injection of STR-01 will be performed after MSC infusion.

Results

We received approval for our clinical trial from the Japanese Pharmaceuticals and Medical Devices Agency on December 12, 2017. The trial will be completed on June 11, 2023. The registration term is 5 years. The recruitment of the patients for this trial started on April 20, 2018, at Sapporo Medical University Hospital in Japan.

Conclusions

Our phase 2 study will aim to address the safety and efficacy of the intravenous infusion of MSCs for patients with chronic brain injury. The use of STR-01 has been performed for patients with cerebral infarction and spinal cord injury, providing encouraging results. The potential therapeutic efficacy of the systemic administration of autoserum-expanded autologous MSCs for chronic brain injury should be evaluated, given its safety and promising results for stroke and spinal cord injury.

Trial Registration

Japan Medical Association Center for Clinical Trials JMA-IIA00333; https://tinyurl.com/nzkdfnbc

International Registered Report Identifier (IRRID)

DERR1-10.2196/37898

Effects of obesity on CC16 and their potential role in overweight/obese asthma.
Houman Goudarzi, Hirokazu Kimura, Hiroki Kimura, Hironi Makita, Munehiro Matsumoto, Nozomu Takei, Kaoruko Shimizu, Masaru Suzuki, Taku Watanabe, Eiki Kikuchi, Hiroshi Ohira, Ichizo Tsujino, Jun Sakakibara-Konishi, Naofumi Shinagawa, Noriharu Shijubo, Hirokazu Sato, Katsunori Shigehara, Kichizo Kaga, Yasuhiro Hida, Soichi Murakami, Yuma Ebihara, Akinobu Nakamura, Hideaki Miyoshi, Satoshi Hirano, Nobuyuki Hizawa, Tatsuya Atsumi, Shau-Ku Huang, Yoichi M Ito, Masaharu Nishimura, Satoshi Konno
Respiratory research, 23, 1, 174, 174, 2022年06月29日, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Club cell secretory protein-16 (CC16) is a major anti-inflammatory protein expressed in the airway; however, the potential role of CC16 on overweight/obese asthma has not been assessed. In this study, we examined whether obesity reduces airway/circulatory CC16 levels using experimental and epidemiological studies. Then, we explored the mediatory role of CC16 in the relationship of overweight/obesity with clinical asthma measures. METHODS: Circulating CC16 levels were assessed by ELISA in three independent human populations, including two groups of healthy and general populations and asthma patients. The percentage of cells expressing club markers in obese vs. non-obese mice and human airways was determined by immunohistochemistry. A causal mediation analysis was conducted to determine whether circulatory CC16 acted as a mediator between overweight/obesity and clinical asthma measures. RESULTS: BMI was significantly and monotonously associated with reduced circulating CC16 levels in all populations. The percentage of CC16-expressing cells was reduced in the small airways of both mice and humans with obesity. Finally, mediation analysis revealed significant contributions of circulatory CC16 in the association between BMI and clinical asthma measures; 21.8% of its total effect in BMI's association with airway hyperresponsiveness of healthy subjects (p = 0.09), 26.4% with asthma severity (p = 0.030), and 23% with the required dose of inhaled corticosteroid (p = 0.042). In logistic regression analysis, 1-SD decrease in serum CC16 levels of asthma patients was associated with 87% increased odds for high dose ICS requirement (p < 0.001). CONCLUSIONS: We demonstrate that airway/circulating CC16, which is inversely associated with BMI, may mediate development and severity in overweight/obese asthma.

HOPS-R01 phase II trial evaluating neoadjuvant S-1 therapy for resectable pancreatic adenocarcinoma.
Toru Nakamura, Tsuyoshi Hayashi, Yasutoshi Kimura, Hiroshi Kawakami, Kuniyuki Takahashi, Hirotoshi Ishiwatari, Takuma Goto, Masayo Motoya, Keisuke Yamakita, Yusuke Sakuhara, Michihiro Ono, Eiichi Tanaka, Makoto Omi, Katsuhiko Murakawa, Tomoya Iida, Tamaki Sakurai, Shin Haba, Takehiro Abiko, Yoichi M Ito, Hiroyuki Maguchi, Satoshi Hirano
Scientific reports, 12, 1, 9966, 9966, 2022年06月15日, ［国際誌］
英語, 研究論文（学術雑誌）, Although neoadjuvant therapy (Nac) is recommended for high-risk resectable pancreatic cancer (R-PDAC), evidence regarding specific regimes is scarce. This report aimed to investigate the efficacy of S-1 Nac for R-PDAC. In a multicenter phase II trial, we investigated the efficacy of Nac S-1 (an oral fluoropyrimidine agent containing tegafur, gimeracil, and oteracil potassium) in R-PDAC patients. The protocol involved two cycles of preoperative S-1 chemotherapy, followed by surgery, and four cycles of postoperative S-1 chemotherapy. Two-year progression-free survival (PFS) rates were the primary endpoint. Overall survival (OS) rates and median survival time (MST) were secondary endpoints. Forty-nine patients were eligible, and 31 patients underwent resection following Nac, as per protocol (31/49; 63.3%). Per-protocol analysis included data from 31 patients, yielding the 2-year PFS rate of 58.1%, and 2-, 3-, and 5-year OS rates of 96.8%, 54.8%, and 44.0%, respectively. MST was 49.2 months. Intention-to-treat analysis involved 49 patients, yielding the 2-year PFS rate of 40.8%, and the 2-, 3-, and 5-year OS rates of 87.8%, 46.9%, and 33.9%, respectively. MST was 35.5 months. S-1 single regimen might be an option for Nac in R-PDAC; however, the high drop-out rate (36.7%) was a limitation of this study.

Frequency-Response Relationship Between Exercise and Locomotive Syndrome Across Age Groups: Secondary Analysis of a Nationwide Cross-Sectional Study in Japan.
Satoshi Yamaguchi, Keiko Yamada, Yoichi M Ito, Takeshi Fuji, Kimihito Sato, Takashi Ohe
Modern rheumatology, 33, 3, 617, 622, 2022年06月11日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: This study aimed to clarify the frequency-response relationship between exercise habits and locomotive syndrome in different age groups. METHODS: We analyzed 8,681 independent community dwellers who participated in a nationwide cross-sectional locomotive syndrome study. Participants were divided into young (20-39 years), middle (40-64 years), and old (≥ 65 years) groups. The presence of locomotive syndrome was evaluated using the locomotive syndrome risk tests. Exercise habits were assessed by exercise frequency (almost every day/sometimes/occasionally/never). The association between locomotive syndrome and exercise was assessed using the multiple logistic regression analysis adjusted for participant characteristics for each age category. RESULTS: Overall, 3,528 (41%) participants had locomotive syndrome. In the old group, the risk of locomotive syndrome was lower with an increased exercise frequency. However, this dose-response relationship was not found in the young group. The proportion of locomotive syndrome was lower even in participants who occasionally exercised (1-3 days/month) than those who never exercise in the young and middle age groups. CONCLUSIONS: Regular exercise reduced the risk of locomotive syndrome not only in middle and older adults but also in young adults. Moreover, increasing exercise frequency may provide benefits for locomotive syndrome prevention, especially among older adults.

Phase II study of niraparib in recurrent or persistent rare fraction of gynecologic malignancies with homologous recombination deficiency (JGOG2052).
Hiroshi Asano, Katsutoshi Oda, Kosuke Yoshihara, Yoichi M Ito, Noriomi Matsumura, Muneaki Shimada, Hidemichi Watari, Takayuki Enomoto
Journal of gynecologic oncology, 33, 4, e55, 2022年05月03日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Poly (adenosine diphosphate)-ribose polymerase (PARP) inhibitors for tumors with homologous recombination deficiency (HRD), including pathogenic mutations in BRCA1/2, have been developed. Genomic analysis revealed that about 20% of uterine leiomyosarcoma (uLMS) have HRD, including 7.5%-10% of BRCA1/2 alterations and 4%-6% of carcinomas of the uterine corpus, and 2.5%-4% of the uterine cervix have alterations of BRCA1/2. Preclinical and clinical case reports suggest that PARP inhibitors may be effective against those targets. The Japanese Gynecologic Oncology Group (JGOG) is now planning to conduct a new investigator-initiated clinical trial, JGOG2052. METHODS: JGOG2052 is a single-arm, open-label, multi-center, phase 2 clinical trial to evaluate the efficacy and safety of niraparib monotherapy for a recurrent or persistent rare fraction of gynecologic malignancies with BRCA1/2 mutations except for ovarian cancers. We will independently consider the effect of niraparib for uLMS or other gynecologic malignancies with BRCA1/2 mutations (cohort A, C) and HRD positive uLMS without BRCA1/2 mutations (cohort B). Participants must have 1-3 lines of previous chemotherapy and at least one measurable lesion according to RECIST (v.1.1). Niraparib will be orally administered once a day until lesion exacerbation or unacceptable adverse events occur. Efficacy will be evaluated by imaging through an additional computed tomography scan every 8 weeks. Safety will be measured weekly in cycle 1 and every 4 weeks after cycle 2 by blood tests and physical examinations. The sample size is 16-20 in each of cohort A and B, and 31 in cohort C. Primary endpoint is the objective response rate. TRIAL REGISTRATION: Japan Primary Registries Network (JPRN) Identifier: jRCT2031210264.

Disease activity as a risk factor for venous thromboembolism in rheumatoid arthritis analysed using time-averaged DAS28CRP: a nested case-control study.
Masaru Yoshimura, Yuichiro Fujieda, Masanari Sugawara, Michihito Kono, Masaru Kato, Isao Yokota, Olga Amengual, Yoichi M Ito, Tatsuya Atsumi
Rheumatology international, 42, 11, 1939, 1946, 2022年04月06日, ［国際誌］
英語, 研究論文（学術雑誌）, The objective of this study is to clarify the clinical features and risk factors of venous thromboembolism (VTE) in patients with rheumatoid arthritis (RA). We retrospectively reviewed the prevalence of VTE in RA patients who visited Hokkaido University Hospital from 2010 to 2019 and had more than 2 years of follow-up. To explore the risk to develop VTE, we selected 260 RA patients without VTE (non-VTE) via density sampling and identified the risk factors for VTE by multivariate logistic regression analysis. Univariate conditional logistic regression analysis showed older age (p < 0.0001, Odds Ratio [OR] 1.08, 95% Confidence Interval [CI] 1.04-1.14), increase of the body mass index (BMI) (p = 0.001, OR 1.17, 95% CI 1.06-1.31), higher prevalence of RA-associated lung disease (p = 0.002, OR 2.10, 95% CI 1.33-3.30) and more frequent glucocorticoid usage (p = 0.001, OR 2.09, 95% CI 1.34-3.51) in RA patients was associated with the development of VTE significantly. Furthermore, patients with higher time-averaged disease activity score 28 (DAS28) CRP were at elevated risk (p < 0.0001, OR 3.25, 95% CI 1.94-6.12). In conditional multivariate logistic regression analysis, time averaged DAS28CRP was significantly associated with the development of VTE (p = 0.0001, adjusted OR 3.40, 95% CI 1.77-7.85). Disease activity was identified as a major risk factor of VTE in patients with RA, suggesting that sustained clinical remission could be beneficial for decrease the risk of VTE.

難治性喘息 重症喘息における生物学的製剤の変更に影響する因子の検討
佐々木 真知子, 清水 薫子, 鈴木 正宣, 鈴木 雅, 松本 宗大, 木村 孔一, 中丸 裕爾, 伊藤 陽一, 今野 哲
日本呼吸器学会誌, 11, 増刊, 143, 143, (一社)日本呼吸器学会, 2022年04月
日本語

Subthreshold Change in Glycated Hemoglobin and Body Mass Index After the Initiation of Second-Generation Antipsychotics Among Patients With Schizophrenia or Bipolar Disorder
Ryo Sawagashira, Ryodai Yamamura, Ryo Okubo, Naoki Hashimoto, Shuhei Ishikawa, Yoichi M. Ito, Norihiro Sato, Ichiro Kusumi
The Journal of Clinical Psychiatry, 83, 3, Physicians Postgraduate Press, Inc, 2022年03月30日
研究論文（学術雑誌）

The type rather than the daily dose or number of antipsychotics affects the incidence of hyperglycemic progression
Shuhei Ishikawa, Ryodai Yamamura, Naoki Hashimoto, Ryo Okubo, Ryo Sawagashira, Yoichi M. Ito, Norihiro Sato, Ichiro Kusumi
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 113, 110453, 110453, Elsevier BV, 2022年03月
研究論文（学術雑誌）

Dosimetric advantages of daily adaptive strategy in IMPT for high-risk prostate cancer.
Hiroshi Tamura, Keiji Kobashi, Kentaro Nishioka, Takaaki Yoshimura, Takayuki Hashimoto, Shinichi Shimizu, Yoichi M Ito, Yoshikazu Maeda, Makoto Sasaki, Kazutaka Yamamoto, Hiroyasu Tamamura, Hidefumi Aoyama, Hiroki Shirato
Journal of applied clinical medical physics, 23, 4, e13531, 2022年01月19日, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: To evaluate the dosimetric advantages of daily adaptive radiotherapy (DART) in intensity-modulated proton therapy (IMPT) for high-risk prostate cancer by comparing estimated doses of the conventional non-adaptive radiotherapy (NART) that irradiates according to an original treatment plan through the entire treatment and the DART that uses an adaptive treatment plan generated by using daily CT images acquired before each treatment. METHODS: Twenty-three patients with prostate cancer were included. A treatment plan with 63 Gy (relative biological effectiveness (RBE)) in 21 fractions was generated using treatment planning computed tomography (CT) images assuming that all patients had high-risk prostate cancer for which the clinical target volume (CTV) needs to include prostate and the seminal vesicle (SV) in our treatment protocol. Twenty-one adaptive treatment plans for each patient (total 483 data sets) were generated using daily CT images, and dose distributions were calculated. Using a 3 mm set-up uncertainty in the robust optimization, the doses to the CTV, prostate, SV, rectum, and bladder were compared. RESULTS: Estimated accumulated doses of NART and DART in the 23 patients were 60.81 ± 3.47 Gy (RBE) and 63.24 ± 1.04 Gy (RBE) for CTV D99 (p < 0.01), 62.99 ± 1.28 Gy (RBE) and 63.43 ± 1.33 Gy (RBE) for the prostate D99 (p = 0.2529), and 59.07 ± 5.19 Gy (RBE) and 63.17 ± 1.04 Gy (RBE) for SV D99 (p < 0.001). No significant differences were observed between NART and DART in the estimated accumulated dose for the rectum and bladder. CONCLUSION: Compared with the NART, DART was shown to be a useful approach that can maintain the dose coverage to the target without increasing the dose to the organs at risk (OAR) using the 3 mm set-up uncertainty in the robust optimization in patients with high-risk prostate cancer.

Psychometric properties of the Japanese version of the Occupational Fatigue Exhaustion Recovery Scale among shift-work nurses.
Shinya Yamaguchi, Miho Sato, Naomi Sumi, Yoichi M Ito, Peter C Winwood, Rika Yano
Journal of occupational health, 64, 1, e12325, 2022年01月, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Shift-work nurses are at a higher risk of inadequate recovery from fatigue and developing maladaptive fatigue with significant health consequences. Therefore, it is necessary to monitor fatigue and recovery levels with a reliable scale. We investigated psychometric properties of the Japanese version of the Occupational Fatigue Exhaustion Recovery scale (OFER-J) for shift-work nurses. METHODS: Japanese shift-work nurses responded to self-administered questionnaires at baseline (n = 942) and one month later (n = 334). The confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were conducted to verify the structural validity and the correlation analysis and one-way analysis of variance were conducted to test the construct and discriminative validity. Cronbach's alpha coefficient, intra-class correlation coefficient (ICC), and smallest detectable change (SDC) were calculated to assess reliability. RESULTS: The CFA showed high correlations between the factors and whilst the goodness-of-fit of the three-factor model was suboptimal, it was in an acceptable range. Most modifications included the error covariance of the Acute Fatigue (AF) and Intershift Recovery (IR) items. The EFA showed that Chronic Fatigue (CF) and AF were not clearly separated, indicating that the two AF items dropped out. Construct and discriminative validity were also well indicated. Cronbach's alpha coefficients were 0.75-0.85. Only CF showed sufficient reproductivity (ICC = 0.74). The SDC for CF, AF, and IR was 14.0, 17.1, and 18.7, respectively. CONCLUSIONS: The validity and reliability of the OFER-J were verified as acceptable for shift-work nurses. The OFER-J could contribute to a data-based approach to fatigue management in nursing management practice.

Clinical Characteristics of Patients and Factors Associated with Switching Biologics in Asthma.
Machiko Matsumoto-Sasaki, Kaoruko Simizu, Masanobu Suzuki, Masaru Suzuki, Hirokazu Kimura, Yuji Nakamaru, Yoichi M Ito, Akihiro Honma, Satoshi Konno
Journal of asthma and allergy, 15, 187, 195, 2022年, ［国際誌］
英語, 研究論文（学術雑誌）, Purpose: Biologics have been used increasingly for the treatment of severe asthma. However, established guidelines for the selection, switching, or discontinuation of biologics do not exist. We aimed to identify the clinical characteristics of patients with asthma who required switching biologics and the factors associated with switching biologics. Patients and Methods: This was a retrospective study of 42 patients with severe asthma treated with biologics at the Hokkaido University Hospital between 23rd June 2016 and 30th April 2021, when two biologics were available in Japan. We compared the characteristics of subjects who continued and switched biologics. The time to switch the biologics was assessed by type 2 inflammatory biomarkers, pulmonary function indices, and the presence of comorbidities, including the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) score and aspirin exacerbated respiratory diseases (AERD), using the Kaplan-Meier method and a multivariate Cox proportional hazards model. Results: Eight and five patients were treated by mepolizumab and benralizumab at baseline, respectively among the 31% (13/42) who switched the biologics. Subjects who required switching biologics were characterized by high blood eosinophil counts, younger age, JESREC scores of 11 points or higher, and AERD. The time taken to switch biologics was significantly shorter in the subgroups with high JESREC scores (≥11) or AERD, compared with their counterparts with low JESREC scores or without AERD (both, P < 0.05). JESREC scores of ≥11, but not the presence of AERD, were associated with time to switch biologics. Conclusion: The presence of eosinophilic chronic rhinosinusitis based on JESREC scores of ≥11 and younger age were factors associated with switching biologics in asthma.

Factors associated with mobility decrease leading to disability: a cross-sectional nationwide study in Japan, with results from 8681 adults aged 20-89 years.
Keiko Yamada, Satoshi Yamaguchi, Yoichi M Ito, Takashi Ohe
BMC geriatrics, 21, 1, 651, 651, 2021年11月19日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Mobility decrease leading to disability can gradually develop during early life, however, its related factors are not well clarified. Therefore, we investigate the related factors of mobility decrease at various levels, using nationwide data in Japan. METHODS: In total, 8681 independent community dwellers aged 20-89 years were analysed (average age, 51.6 years; 58.5% women). Three stages of mobility decrease were based on the locomotive syndrome risk test: Stage 1, emerging; Stage 2, progressing; Stage 3, progressed to restrict social engagement. Age was analysed using a simple quadratic function model. RESULTS: The prevalence of Stages 1-3 was 31.6% (n = 2746), 5.8% (n = 504), and 3.2% (n = 278), respectively. On the multivariable logistic regression, increased age in participants aged ≥40 years (stage 1: odds ratio[OR] 1.05-1.20, stage 2: OR 1.04-1.22, stage 3: OR 1.05-1.22), female (stage 1: OR 2.28, 95% confidence interval [CI] 1.99-2.61, stage 2: OR 2.40, 95% CI 1.77-3.25, stage 3: OR 1.80, 95% CI 1.19-2.72), overweight status (stage 1: OR 1.56, 95% CI 1.34-1.82, stage 2: OR 3.19, 95% CI 2.38-4.27, stage 3: OR 2.87, 95% CI 1.90-4.32), hypertension (stage 1: OR 1.20, 95% CI 1.01-1.41, stage 2: OR 1.99, 95% CI 1.49-2.64, stage 3: OR 2.10, 95% CI 1.44-3.05), and diabetes mellitus (stage 1: OR 1.62, 95% CI 1.17-2.24, stage 2: OR 1.57, 95% CI 0.93-2.66, stage 3: OR 2.10, 95% CI 1.13-3.90) were positively associated. The frequency of physical activity/sports, even a few per month, was inversely associated with all stages (stage 1: OR 0.59-0.72, stage 2: OR 0.50-0.67, stage 3: 0.36-0.53). A one-year increase in age had a stronger impact on mobility decrease in older adults than in younger ones. Increased age in participants aged < 40 years and smoking were associated with Stage 1, while intake of various foods was inversely associated with Stages 1 and 2. CONCLUSION: Increased age (< 40 years) was associated with emerging mobility decrease, while that (≥ 40 years) was associated with any levels of mobility decrease. Female, lifestyle habits, including physical activities and overweight status, were associated with mobility decrease at every level.

Particle therapy using protons or carbon ions for cancer patients with cardiac implantable electronic devices (CIED): a retrospective multi-institutional study.
Takayuki Hashimoto, Yusuke Demizu, Haruko Numajiri, Tomonori Isobe, Shigekazu Fukuda, Masaru Wakatsuki, Haruo Yamashita, Shigeyuki Murayama, Shigeyuki Takamatsu, Hiroyuki Katoh, Kazutoshi Murata, Ryosuke Kohno, Takeshi Arimura, Taeko Matsuura, Yoichi M Ito
Japanese journal of radiology, 40, 5, 525, 533, 2021年11月15日, ［国内誌］
英語, 研究論文（学術雑誌）, PURPOSE: To evaluate the outcomes of particle therapy in cancer patients with cardiac implantable electronic devices (CIEDs). MATERIALS AND METHODS: From April 2001 to March 2013, 19,585 patients were treated with proton beam therapy (PBT) or carbon ion therapy (CIT) at 8 institutions. Of these, 69 patients (0.4%, PBT 46, CIT 22, and PBT + CIT 1) with CIEDs (64 pacemakers, 4 implantable cardioverter defibrillators, and 1 with a cardiac resynchronization therapy defibrillator) were retrospectively reviewed. All the patients with CIEDs in this study were treated with the passive scattering type of particle beam therapy. RESULTS: Six (13%) of the 47 PBT patients, and none of the 23 CIT patients experienced CIED malfunctions (p = 0.105). Electrical resets (7) and over-sensing (3) occurred transiently in 6 patients. The distance between the edge of the irradiation field and the CIED was not associated with the incidence of malfunctions in 20 patients with lung cancer. A larger field size had a higher event rate but the test to evaluate trends as not statistically significant (p = 0.196). CONCLUSION: Differences in the frequency of occurrence of device malfunctions for patients treated with PBT and patients treated with CIT did not reach statistical significance. The present study can be regarded as a benchmark study about the incidence of malfunctioning of CIED in passive scattering particle beam therapy and can be used as a reference for active scanning particle beam therapy.

Development and validation of a prediction model based on the organ-based metabolic tumor volume on FDG-PET in patients with differentiated thyroid carcinoma.
Yuko Uchiyama, Kenji Hirata, Shiro Watanabe, Shozo Okamoto, Tohru Shiga, Kazufumi Okada, Yoichi M Ito, Kohsuke Kudo
Annals of nuclear medicine, 35, 11, 1223, 1231, SPRINGER, 2021年11月, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Although patients with differentiated thyroid cancer (DTC) generally have a good prognosis, patients with a large metabolic tumor volume (MTV) on FDG-PET may experience poor clinical courses. We measured organ-based MTVs and tested its prognostic performance in comparison to conventional MTV (cMTV). METHODS: We retrospectively analyzed the cases of 280 patients who received their first I-131 therapy in 2003-2014 at our hospital and showed an FDG-avid metastatic lesion. We randomly divided the patients into training (n = 190) and validation (n = 90) datasets. We classified the MTVs as MTVneck-node, MTVdistant-node, MTVlung, MTVbone, and MTVother-organs and tested with/without dichotomization vis-à-vis overall survival (OS). Based on the estimated weighting coefficients of the organ-based MTVs, we propose a new index: the adjusted whole-body MTV (aMTV). Using the validation dataset, we compared the aMTV with cMTV for predicting OS. RESULTS: In a univariate analysis, MTVdistant-node and MTVother-organs were more strongly correlated with the OS than the dichotomized forms, whereas the dichotomized forms of MTVneck-node, MTVlung, and MTVbone were more strongly correlated with OS than the continuous variables. The aMTV was thus expressed as 0.69 × dic(MTVneck-node) + 0.02 × MTVdistant-node + 1.05 × dic(MTVlung) + 1.58 × dic(MTVbone) + 0.01 × MTVother-organs, where dic(x) represents 0 or 1 based on the optimized cut-off. In the model evaluation using the validation group, aMTV was a significant predictor of OS with a higher c-index (0.7676) than cMTV (0.7218). CONCLUSION: In DTC patients with FDG-avid metastasis before I-131 therapy, all organ-based MTVs were significant predictors of prognosis. As the aMTV outperformed the cMTV for predicting prognoses, we recommend measuring the MTV on an organ basis.

がん治療医・緩和ケアスタッフを対象としたターミナルケア態度尺度を用いた意識調査　　　　　　　　　　　　　　　
熊井 正貴, 加藤 信太郎, 小柳 遼, 敦賀 健吉, 伊藤 陽一, 山田 武宏, 川本 泰之, 武隈 洋, 菅原 満, 小松 嘉人
Palliative Care Research, 16, Suppl._Hokkaido, S492, S492, (NPO)日本緩和医療学会, 2021年10月
日本語

Determination of brain tumor recurrence using 11 C-methionine positron emission tomography after radiotherapy.
Shigeru Yamaguchi, Kenji Hirata, Michinari Okamoto, Eku Shimosegawa, Jun Hatazawa, Ryuichi Hirayama, Naoki Kagawa, Haruhiko Kishima, Noboru Oriuchi, Masazumi Fujii, Kentaro Kobayashi, Hiroyuki Kobayashi, Shunsuke Terasaka, Ken-Ichi Nishijima, Yuji Kuge, Yoichi M Ito, Hiroshi Nishihara, Nagara Tamaki, Tohru Shiga
Cancer science, 112, 10, 4246, 4256, WILEY, 2021年10月, ［国際誌］
英語, 研究論文（学術雑誌）, We conducted a prospective multicenter trial to compare the usefulness of 11 C-methionine (MET) and 18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying tumor recurrence. Patients with clinically suspected tumor recurrence after radiotherapy underwent both 11 C-MET and 18 F-FDG PET. When a lesion showed a visually detected uptake of either tracer, it was surgically resected for histopathological analysis. Patients with a lesion negative to both tracers were revaluated by magnetic resonance imaging (MRI) at 3 months after the PET studies. The primary outcome measure was the sensitivity of each tracer in cases with histopathologically confirmed recurrence, as determined by the McNemar test. Sixty-one cases were enrolled, and 56 cases could be evaluated. The 38 cases where the lesions showed uptake of either 11 C-MET or 18 F-FDG underwent surgery; 32 of these cases were confirmed to be subject to recurrence. Eighteen cases where the lesions showed uptake of neither tracer received follow-up MRI; the lesion size increased in one of these cases. Among the cases with histologically confirmed recurrence, the sensitivities of 11 C-MET PET and 18 F-FDG PET were 0.97 (32/33, 95% confidence interval [CI]: 0.85-0.99) and 0.48 (16/33, 95% CI: 0.33-0.65), respectively, and the difference was statistically significant (P < .0001). The diagnostic accuracy of 11 C-MET PET was significantly better than that of 18 F-FDG PET (87.5% vs. 69.6%, P = .033). No examination-related adverse events were observed. The results of the study demonstrated that 11 C-MET PET was superior to 18 F-FDG PET for discriminating between tumor recurrence and radiation-induced necrosis.

Developing a questionnaire on the quality of working life for female medical and healthcare professionals.
Kikuko Taketomi, Yoichi M Ito, Eriko Tokunaga, Yuko O Hirano, Yuriko Fujino, Akiko Chishaki
Industrial health, 59, 6, 371, 382, 2021年09月28日, ［国内誌］
英語, 研究論文（学術雑誌）, This study aimed to develop a questionnaire on the quality of working life among female medical and healthcare professionals and examine its validity and reliability. The questionnaire was developed from an item pool drawing on the literature. The four trait scales included 40 items, covering female-specific stress in continuing a career, stress of lifestyle in maintaining personal values, job satisfaction and social support network. The questionnaire's validity and reliability were assessed using data from 1,784 female doctors, dentists, and nurses. Validity was examined using exploratory factor analysis on each trait for construct validity, and multitrait scaling analysis for convergent and discriminant validity. Reliability was tested using Cronbach's alpha for trait subscales and scales. Exploratory factor analysis on each trait was convergent. One trait derived three subscales, and another two. The remaining two traits were convergent for one factor. Multitrait scaling analysis showed that all scales and subscales were independent. The questionnaire was therefore internally consistent and had construct validity. Cronbach's alpha was 0.85 for the total and between 0.72 and 0.83 for the subscales. These results validate the four-trait combination questionnaire and suggest that it would be suitable for use in future research, perhaps in combination with other existing scales.

Elevated serum CYFRA 21-1 level as a diagnostic marker for thymic carcinoma.
Haruhiko Shiiya, Hideki Ujiie, Yasuhiro Hida, Tatsuya Kato, Kichizo Kaga, Satoru Wakasa, Eiki Kikuchi, Naofumi Shinagawa, Kazufumi Okada, Yoichi M Ito, Yoshihiro Matsuno
Thoracic cancer, 12, 21, 2933, 2942, 2021年09月27日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: No useful tumor markers have been identified for the diagnosis of thymic carcinomas. Serum cytokeratin 19 fragment, measured using the CYFRA 21-1 immunoassay, is used as a tumor marker for squamous cell carcinomas in various malignant tumors. Here, we evaluated the value of CYFRA 21-1 in diagnosing thymic carcinoma. METHODS: We retrospectively reviewed 94 patients with pathological diagnoses of thymic carcinoma or thymoma (32 and 62 patients, respectively) who were referred to our departments between January 2000 and March 2019. Primary outcomes included tumor marker levels and their diagnostic accuracy. RESULTS: Patients with thymic carcinoma were significantly more likely to be male (thymic carcinoma, 68.8%; thymoma, 40.3%; p = 0.02), have an advanced TNM stage (p < 0.01), and a significantly higher CYFRA 21-1 level than those with thymoma (thymic carcinoma: median = 4.2 ng/ml; interquartile range [IQR] = 2.1-6.1 ng/ml vs. thymoma: median = 1.2 ng/ml; IQR = 0.9-1.7 ng/ml; p < 0.01). Receiver operating characteristic curves demonstrated that the area under the curve for CYFRA 21-1 to distinguish thymic carcinoma from thymoma was 0.86 (95% confidence interval [CI]: 0.74-0.93; cutoff = 2.7 ng/ml; sensitivity = 68.8%; specificity = 95.2%). Multivariable analysis demonstrated that CYFRA 21-1 (odds ratio = 25.6; 95% CI: 4.6-141.6; p < 0.01) was an independent predictor for thymic carcinoma after adjusting for TNM stage. CONCLUSIONS: Serum CYFRA 21-1 level may help in diagnosing thymic carcinoma.

Association of abdominal visceral adiposity with sputum IL-5 levels in asthma.
Houman Goudarzi, Hirokazu Kimura, Hironi Makita, Yuki Abe, Akira Oguma, Michiko Sato, Munehiro Matsumoto, Nozomu Takei, Hiroki Kimura, Kaoruko Shimizu, Masaru Suzuki, Yoichi M Ito, Masaharu Nishimura, Satoshi Konno
Allergology international : official journal of the Japanese Society of Allergology, 71, 1, 137, 139, 2021年09月14日, ［国際誌］
英語

Thrombocytopenia Associated with Unrecognized Non-Alcoholic Fatty Liver Disease Is an Independent Predictor of Perioperative Significant Blood Loss in Cervical Laminoplasty.
Ryota Suzuki, Yoshinao Koike, Masahiro Ota, Tsutomu Endo, Yuichiro Hisada, Takeru Tsujimoto, Masahiro Kanayama, Yoichi M Ito, Hideki Sudo, Akira Iwata, Katsuhisa Yamada, Norimasa Iwasaki, Masahiko Takahata
World neurosurgery, 155, e797-e804, 2021年09月09日, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: To identify risk factors for significant blood loss (SBL) in cervical laminoplasty, especially regarding thrombocytopenia and coagulopathy resulting from non-alcoholic fatty liver disease (NAFLD). METHODS: We retrospectively investigated differences in patient background data, laboratory data at the time of admission, and surgery-related data of 317 patients who underwent cervical laminoplasty and were divided into SBL (estimated blood loss [EBL] + drainage [D] ≥500 g) and non-SBL (EBL + D < 500 g) groups. To evaluate liver status, we used the fibrous 4 index and considered fibrous 4 index ≥1.85 as a representative phenotype for NAFLD with liver fibrosis. In addition, the risk factor for perioperative SBL was investigated using multiple logistic regression analysis, and the cutoff value was calculated. RESULTS: Incidence of perioperative SBL in cervical laminoplasty was 7.3% (23/317). Compared with the non-SBL group, the SBL group demonstrated significantly lower platelet count (PLT), lower aspartate aminotransferase, longer operation time, and greater number of opened laminae. According to multivariate analysis, lower PLT and a greater number of opened laminae were identified as significant risk factors for perioperative SBL. The cutoff value of PLT for predicting SBL was determined to be 16.7 × 104/μL using a receiver operating characteristic curve. The liver fibrosis group revealed significantly lower PLT and greater EBL + D than the non-liver fibrosis group. CONCLUSIONS: Thrombocytopenia is an independent predictor of perioperative SBL in cervical laminoplasty. Thus, patients with mild thrombocytopenia that may be associated with NAFLD must be carefully monitored to avoid perioperative SBL.

Work environment for hospital nurses in Japan: The relationships between nurses' perceptions of their work environment and nursing outcomes.
Yasuko Ogata, Kana Sato, Yoshimi Kodama, Noriko Morioka, Kikuko Taketomi, Yuki Yonekura, Kimiko Katsuyama, Sachiko Tanaka, Midori Nagano, Yoichi M Ito, Katsuya Kanda
Nursing open, 8, 5, 2470, 2487, WILEY, 2021年09月, ［国際誌］
英語, 研究論文（学術雑誌）, AIM: To investigate nurses' perceptions of their work environment and to investigate the relationships between variables measuring the work environment (WE) and nursing outcomes (NOs ). DESIGN: A 2-year prospective longitudinal survey (2013-2015). METHOD(S): Descriptive statistics of nurse demographics, organizational WE and NOs were calculated by position. The associations between Practice Environment Scale of the Nursing Work Index (PES-NWI) and NOs were examined for each unit. RESULTS: The participants were 2,992 staff nurses, 137 nurse managers (NMs), and 8 chief nursing officers in Phase 1 and 7,849, 371 and 23 in Phase 2, respectively. The higher the job position, the better the WE was rated. The higher the PES-NWI scores, the better the outcomes. Descriptive statistics about organizational WEs and NOs and the statistically significant associations between the two were identified.

Exploratory clinical trial on the safety and capability of dMD-001 in lumbar disc herniation: Study protocol for a first-in-human pilot study.
Katsuhisa Yamada, Maeda Kenichiro, Yoichi M Ito, Fujio Inage, Toshiyuki Isoe, Nozomi Yokota, Osamu Sugita, Norihiro Sato, Khin Khin Tha, Norimasa Iwasaki, Teruyo Arato, Hideki Sudo
Contemporary clinical trials communications, 23, 100805, 100805, 2021年09月, ［国際誌］
英語, 研究論文（学術雑誌）, Herniated nucleus pulposus (NP), one of the most common diseases of the spine, is surgically treated by removing the sequestered NP. However, intervertebral disc (IVD) defects may remain after discectomy, leading to inadequate tissue healing and predisposing patients to IVD degeneration. An acellular, bioresorbable, ultra-purified alginate (UPAL) gel (dMD-001) implantation system can be used to fill any IVD defects in order to prevent IVD degeneration after discectomy. This first-in-human pilot study aims to determine the feasibility, safety, and perceived patient response to a combined treatment involving discectomy and UPAL gel implantation for herniated NP. We designed a one-arm, double-centre, open-label, pilot trial. The study started in November 2018 and will run until a sample of 40 suitable participants is established. Patients aged 20-49 years, diagnosed with isolated lumbar IVD herniation and scheduled for discectomy represent suitable candidates. All eligible participants who provide informed consent undergo standard discectomy followed by UPAL gel implantation. The primary outcomes of the trial will be the feasibility and safety of the procedure. Secondary outcomes will include self-assessed clinical scores and magnetic resonance imaging-based measures of morphological and compositional quality of the IVD tissue. Initial outcomes will be published at 24 weeks. Analysis of feasibility and safety will be performed using descriptive statistics. Both intention-to-treat and per-protocol analyses of treatment trends of effectiveness will be conducted.

Close association between non-alcoholic fatty liver disease and ossification of the posterior longitudinal ligament of the spine.
Tsutomu Endo, Yoshinao Koike, Hideaki Miyoshi, Yuichiro Hisada, Ryo Fujita, Ryota Suzuki, Masaru Tanaka, Takeru Tsujimoto, Yukitoshi Shimamura, Yuichi Hasegawa, Masahiro Kanayama, Tomoyuki Hashimoto, Fumihiro Oha, Naoki Noro, Kiyofumi Komano, Misaki Ishii, Yoichi M Ito, Norimasa Iwasaki, Masahiko Takahata
Scientific reports, 11, 1, 17412, 17412, NATURE PORTFOLIO, 2021年08月31日, ［国際誌］
英語, 研究論文（学術雑誌）, Ossification of the posterior longitudinal ligament (OPLL) of the spine is a disease of unknown etiology occurring frequently in individuals with metabolic disturbances. Obesity has been suggested as a potential risk factor for the severity of OPLL. We aimed to investigate whether non-alcoholic fatty liver disease (NAFLD) is associated with OPLL severity. We assessed the severity of NAFLD by a liver-to-spleen (L/S) ratio on computed tomography (CT) scans of 85 symptomatic OPLL patients at a single institution in Japan. We also assessed the severity of OPLL by CT reconstruction sagittal and axial images. The prevalence of NAFLD in middle-aged patients (age < 70 years, n = 50) was 80.3%, which was 2.5-8 times higher than that in the general Japanese population (9-30%). The ossification index of the spinal ligaments increased in proportion to the severity of fatty liver. The L/S ratio was revealed as a significant risk factor associated with the total ossification index (standardized β: -0.40, 95% confidence interval - 54.34 to - 4.22). This study suggests the potential contribution of NAFLD to the progression of OPLL. The close association between NAFLD and OPLL demonstrated in this study warrants further study to elucidate the causal nature of this relationship.

Three-day regimen of oseltamivir for post-exposure prophylaxis of influenza in hospital wards: a study protocol for a prospective, multi-center, single-arm trial.
Nobuhisa Ishiguro, Yoichi M Ito, Sumio Iwasaki, Miki Nagao, Hideki Kawamura, Shinichiro Kanai, Yoko Nukui, Koichi Tokuda, Takayuki Miyara, Hidetoshi Igari, Koichi Yamada, Hiroki Chikumi, Chiaki Sano, Ryuji Koike, Tetsuya Yagi, Nobuo Murakami
BMC infectious diseases, 21, 1, 887, 887, BMC, 2021年08月30日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: In a previous retrospective observational study, a 3-day regimen of oseltamivir as post-exposure prophylaxis (PEP) for preventing transmission of influenza in wards was shown to be comparable to 7- to 10-day regimens provided index cases were immediately separated from close contacts. In order to confirm the efficacy of a 3-day regimen, we started to conduct a prospective, multi-center, single-arm trial. METHODS: This study is a prospective, multi-center, single-arm study designed by the Sectional Meeting of Clinical Study, Japan Infection Prevention and Control Conference for National and Public University Hospitals. Index patients with influenza are prescribed a neuraminidase inhibitor and are discharged immediately or transferred to isolation rooms. The close contacts are given oseltamivir as 75 mg capsules once daily for adults or 2 mg/kg (maximum of 75 mg) once daily for children for 3 days as PEP. All close contacts are monitored for development of influenza for 7 days after starting PEP. DISCUSSION: A 3-day regimen of oseltamivir as PEP has advantages over 7- to 10-day regimens in terms of costs, medication adherence and adverse effects. Trial registration The Institutional Review Board of Hokkaido University Hospital for Clinical Research, 015-0518, registered on November 11, 2016. UMIN Clinical Trials Registry, UMIN000024458, disclosed on October 31, 2016. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027881 . Japan Registry of Clinical Trials, jRCTs011180015, disclosed on March 14, 2019. https://jrct.niph.go.jp/latest-detail/jRCTs011180015.

Efficacy and safety of second-line axitinib in octogenarians with metastatic renal cell carcinoma.
Yasutomo Nakai, Ario Takeuchi, Takahiro Osawa, Takahiro Kojima, Tomohiko Hara, Mikio Sugimoto, Masatoshi Eto, Keita Minami, Kosuke Ueda, Michinobu Ozawa, Motohide Uemura, Yasuyuki Miyauchi, Kojiro Ohba, Akira Kashiwagi, Masaya Murakami, Tomokazu Sazuka, Hiroaki Yasumoto, Shuichi Morizane, Yoshihide Kawasaki, Daichi Morooka, Toru Shimazui, Yoshiaki Yamamoto, Hiroshi Nakagomi, Ryotaro Tomida, Yoichi M Ito, Sachiyo Murai, Hiroshi Kitamura, Hiroyuki Nishiyama, Nobuo Shinohara
Journal of geriatric oncology, 12, 5, 834, 837, ELSEVIER, 2021年06月, ［国際誌］
英語

Assessment of the confidence interval in the multivariable normal tissue complication probability model for predicting radiation-induced liver disease in primary liver cancer.
Anussara Prayongrat, Natchalee Srimaneekarn, Sira Sriswasdi, Yoichi M Ito, Norio Katoh, Masaya Tamura, Yasuhiro Dekura, Chie Toramatsu, Chonlakiet Khorprasert, Napapat Amornwichet, Petch Alisanant, Yuichi Hirata, Anthony Hayter, Hiroki Shirato, Shinichi Shimizu, Keiji Kobashi
Journal of radiation research, 62, 3, 483, 493, OXFORD UNIV PRESS, 2021年05月12日, ［国際誌］
英語, 研究論文（学術雑誌）, We developed a confidence interval-(CI) assessing model in multivariable normal tissue complication probability (NTCP) modeling for predicting radiation-induced liver disease (RILD) in primary liver cancer patients using clinical and dosimetric data. Both the mean NTCP and difference in the mean NTCP (ΔNTCP) between two treatment plans of different radiotherapy modalities were further evaluated and their CIs were assessed. Clinical data were retrospectively reviewed in 322 patients with hepatocellular carcinoma (n = 215) and intrahepatic cholangiocarcinoma (n = 107) treated with photon therapy. Dose-volume histograms of normal liver were reduced to mean liver dose (MLD) based on the fraction size-adjusted equivalent uniform dose. The most predictive variables were used to build the model based on multivariable logistic regression analysis with bootstrapping. Internal validation was performed using the cross-validation leave-one-out method. Both the mean NTCP and the mean ΔNTCP with 95% CIs were calculated from computationally generated multivariate random sets of NTCP model parameters using variance-covariance matrix information. RILD occurred in 108/322 patients (33.5%). The NTCP model with three clinical and one dosimetric parameter (tumor type, Child-Pugh class, hepatitis infection status and MLD) was most predictive, with an area under the receiver operative characteristics curve (AUC) of 0.79 (95% CI 0.74-0.84). In eight clinical subgroups based on the three clinical parameters, both the mean NTCP and the mean ΔNTCP with 95% CIs were able to be estimated computationally. The multivariable NTCP model with the assessment of 95% CIs has potential to improve the reliability of the NTCP model-based approach to select the appropriate radiotherapy modality for each patient.

Acute Oral Calcium Suppresses Food Intake Through Enhanced Peptide-YY Secretion Mediated by the Calcium-Sensing Receptor in Rats.
Akiho Igarashi, Shono Ogasawara, Ryo Takagi, Kazufumi Okada, Yoichi M Ito, Hiroshi Hara, Tohru Hira
The Journal of nutrition, 151, 5, 1320, 1328, 2021年05月11日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Dietary calcium has been proposed to reduce appetite in human studies. Postprandial satiety is mainly controlled by gut hormones. However, the effect of calcium on appetite and the role of gut hormones remain unclear. OBJECTIVES: We examined whether oral administration of calcium reduces food intake in rats and investigated the underlying mechanism. METHODS: Male Sprague Dawley rats (8-12 wk old) were used after an overnight fastifffng. In a series of 2 trials with 1-wk interval between challenges, food intake was measured 0.5-24 h after oral gavage of a vehicle (saline containing 1.5% carboxymethyl cellulose) as the control treatment, or the vehicle containing various calcium compounds [calcium chloride (CaCl2), calcium carbonate, calcium lactate, in a random order] at 150 mg calcium/kg dose. A conditional taste aversion test was conducted. In separate experiments, plasma calcium and gut hormone concentrations were measured 15 or 30 min after oral administration of the calcium compounds. In anesthetized rats, portal peptide-YY (PYY) concentrations were measured after intraluminal administration of a liquid meal with or without additional calcium. RESULTS: Oral CaCl2 reduced food intake acutely (30 min, ∼20%, P < 0.05) compared with control rats, without taste aversion. Plasma PYY concentration was higher (100%, P < 0.05) in CaCl2-preloaded rats than in control rats, 15 min after administration. In anesthetized rats, luminal meal + CaCl2 induced a 4-fold higher increase in plasma PYY than the control treatment did. Oral administration of a calcium-sensing receptor (CaSR) agonist suppressed food intake (∼30%, P < 0.05), but CaCl2 and CaSR agonist did not suppress food intake under treatment with a PYY receptor antagonist. Furthermore, the CaSR antagonist attenuated the effect of CaCl2 on food intake. CONCLUSIONS: CaCl2 suppresses food intake partly by increasing CaSR-mediated PYY secretion in rats. Our findings could at least partially explain the satiating effect of calcium.

Effects of Repeated 131I-Meta-Iodobenzylguanidine Radiotherapy on Tumor Size and Tumor Metabolic Activity in Patients with Metastatic Neuroendocrine Tumors.
Keiichiro Yoshinaga, Takashige Abe, Shozo Okamoto, Yuko Uchiyama, Osamu Manabe, Yoichi M Ito, Naomi Tamura, Natsue Ito, Naho Yoshioka, Komei Washino, Nobuo Shinohara, Nagara Tamaki, Tohru Shiga
Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 62, 5, 685, 694, SOC NUCLEAR MEDICINE INC, 2021年05月10日, ［国際誌］
英語, 研究論文（学術雑誌）, 131I-meta-iodobenzylguanidine (131I-MIBG) radiotherapy has shown some survival benefits in metastatic neuroendocrine tumors (NETs). European Association of Nuclear Medicine clinical guidelines for 131I-MIBG radiotherapy suggest a repeated treatment protocol, although none currently exists. The existing single-high-dose 131I-MIBG radiotherapy (444 MBq/kg) has been shown to have some benefits for patients with metastatic NETs. However, this protocol increases adverse effects and requires alternative therapeutic approaches. Therefore, the aim of this study was to evaluate the effects of repeated 131I-MIBG therapy on tumor size and tumor metabolic response in patients with metastatic NETs. Methods: Eleven patients with metastatic NETs (aged 49.2 ± 16.3 y) prospectively received repeated 5,550-MBq doses of 131I-MIBG therapy at 6-mo intervals. In total, 31 treatments were performed. The mean number of treatments was 2.8 ± 0.4, and the cumulative 131I-MIBG dose was 15,640.9 ± 2,245.1 MBq (286.01 MBq/kg). Tumor response was observed by CT and 18F-FDG PET or by 18F-FDG PET/CT before and 3-6 mo after the final 131I-MIBG treatment. Results: On the basis of the CT findings with RECIST, 3 patients showed a partial response and 6 patients showed stable disease. The remaining 2 patients showed progressive disease. Although there were 2 progressive-disease patients, analysis of all patients showed no increase in summed length diameter (median, 228.7 mm [interquartile range (IQR), 37.0-336.0 mm] to 171.0 mm [IQR, 38.0-270.0 mm]; P = 0.563). In tumor region-based analysis with partial-response and stable-disease patients (n = 9), 131I-MIBG therapy significantly reduced tumor diameter (79 lesions; median, 16 mm [IQR, 12-22 mm] to 11 mm [IQR, 6-16 mm]; P < 0.001). Among 5 patients with hypertension, there was a strong trend toward systolic blood pressure reduction (P = 0.058), and diastolic blood pressure was significantly reduced (P = 0.006). Conclusion: Eighty-two percent of metastatic NET patients effectively achieved inhibition of disease progression, with reduced tumor size and reduced metabolic activity, through repeated 131I-MIBG therapy. Therefore, this relatively short-term repeated 131I-MIBG treatment may have potential as one option in the therapeutic protocol for metastatic NETs. Larger prospective studies with control groups are warranted.

Log-linear relationship between endogenous insulin secretion and glycemic variability in patients with type 2 diabetes on continuous glucose monitoring.
Aika Miya, Akinobu Nakamura, Takahisa Handa, Hiroshi Nomoto, Hiraku Kameda, Kyu Yong Cho, So Nagai, Yoichi M Ito, Hideaki Miyoshi, Tatsuya Atsumi
Scientific reports, 11, 1, 9057, 9057, NATURE RESEARCH, 2021年04月27日, ［国際誌］
英語, 研究論文（学術雑誌）, The contribution of endogenous insulin secretion to glycemic variability (GV) may differ between patients with impaired insulin secretion and those with preserved secretion. Our objective was to determine the linearity of the relationship between fasting C-peptide (CPR) as a marker of endogenous insulin secretion and GV in type 2 diabetes (T2DM), regardless of the type of antidiabetic treatment. We conducted a prospective observational study using continuous glucose monitoring obtained from 284 Japanese outpatients with T2DM with various HbA1c values and antidiabetic treatment. We constructed a prediction curve of base-line CPR versus coefficient of variation (CV) and identified the clinical factors associated with CV using multiple regression analysis. Fasting CPR showed a significant negative log-linear relationship with CV (P < 0.0001), and the latter being strikingly high in the low-CPR group. The multiple regression analysis showed that low CPR was an independent predictor of high CV (P < 0.0001). The significant correlations were sustained in both patients with/without insulin treatment. The contribution of endogenous insulin secretion to GV depends on the extent of insulin secretion impairment. Fasting CPR may represent a useful indicator of GV instability in T2DM.

Mediating Factors Between Parental Socioeconomic Status and Small for Gestational Age in Infants: Results from the Hokkaido Study on Environment and Children’s Health
Naomi Tamura, Tomoyuki Hanaoka, Kumiko Ito, Atsuko Araki, Chihiro Miyashita, Sachiko Ito, Sumitaka Kobayashi, Yoichi Ito, Hisanori Minakami, Kazutoshi Cho, Toshiaki Endo, Tsuyoshi Baba, Kazuo Sengoku, Toshinobu Miyamoto, Katsuhiko Ogasawara, Reiko Kishi
Maternal and Child Health Journal, 25, 4, 645, 655, Springer Science and Business Media LLC, 2021年04月
研究論文（学術雑誌）

Intravenous infusion of auto serum-expanded autologous mesenchymal stem cells in spinal cord injury patients: 13 case series.
Osamu Honmou, Toshihiko Yamashita, Tomonori Morita, Tsutomu Oshigiri, Ryosuke Hirota, Satoshi Iyama, Junji Kato, Yuichi Sasaki, Sumio Ishiai, Yoichi M Ito, Ai Namioka, Takahiro Namioka, Masahito Nakazaki, Yuko Kataoka-Sasaki, Rie Onodera, Shinichi Oka, Masanori Sasaki, Stephen G Waxman, Jeffery D Kocsis
Clinical neurology and neurosurgery, 203, 106565, 106565, ELSEVIER, 2021年04月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Although spinal cord injury (SCI) is a major cause of disability, current therapeutic options remain limited. Recent progress in cellular therapy with mesenchymal stem cells (MSCs) has provided improved function in animal models of SCI. We investigated the safety and feasibility of intravenous infusion of MSCs for SCI patients and assessed functional status after MSC infusion. METHODS: In this phase 2 study of intravenous infusion of autologous MSCs cultured in auto-serum, a single infusion of MSCs under Good Manufacturing Practice (GMP) production was delivered in 13 SCI patients. In addition to assessing feasibility and safety, neurological function was assessed using the American Spinal Injury Association Impairment Scale (ASIA), International Standards for Neurological and Functional Classification of Spinal Cord (ISCSCI-92). Ability of daily living was assessed using Spinal Cord Independence Measure (SCIM-III). The study protocol was based on advice provided by the Pharmaceuticals and Medical Devices Agency in Japan. The trial was registered with the Japan Medical Association (JMA-IIA00154). RESULTS: No serious adverse events were associated with MSC injection. There was neurologic improvement based on ASIA grade in 12 of the 13 patients at six months post-MSC infusion. Five of six patients classified as ASIA A prior to MSC infusion improved to ASIA B (3/6) or ASIA C (2/6), two ASIA B patients improved to ASIA C (1/2) or ASIA D (1/2), five ASIA C patients improved and reached a functional status of ASIA D (5/5). Notably, improvement from ASIA C to ASIA D was observed one day following MSC infusion for all five patients. Assessment of both ISCSCI-92, SCIM-III also demonstrated functional improvements at six months after MSC infusion, compared to the scores prior to MSC infusion in all patients. CONCLUSION: While we emphasize that this study was unblinded, and does not exclude placebo effects or a contribution of endogenous recovery or observer bias, our observations provide evidence supporting the feasibility, safety and functional improvements of infused MSCs into patients with SCI.

ロボット支援腹腔鏡下前立腺全摘除術における神経温存が健康関連QOLに及ぼす影響
大澤 崇宏, 安部 崇重, 松本 隆児, 菊地 央, 山田 修平, 古御堂 純, 宮田 遥, 村井 祥代, 伊藤 陽一, 篠原 信雄
泌尿器外科, 34, 3, 321, 321, 医学図書出版(株), 2021年03月
日本語

Comparison of Health-Related Quality of Life Between Japanese and American Patients with Bladder Cancer as Measured by a Newly Developed Japanese Version of the Bladder Cancer Index
Takahiro Osawa, John T. Wei, Takashige Abe, Michitaka Honda, Karl T. Rew, Rod Dunn, Shuhei Yamada, Jun Furumido, Hiroshi Kikuchi, Ryuji Matsumoto, Yasuyuki Sato, Toni Harabayashi, Norikata Takada, Keita Minami, Ken Morita, Akira Kashiwagi, Shunichi Fukuhara, Sachiyo Murai, Yoichi M. Ito, Katsuhiko Ogasawara, Nobuo Shinohara
BLADDER CANCER, 7, 1, 61, 69, IOS PRESS, 2021年
英語, 研究論文（学術雑誌）, INTRODUCTION: The aim of this study is to characterize health related quality of life (HRQOL) in Japanese patients after bladder cancer surgery and to perform cross-cultural comparison between Japanese and American patients.METHODS: Firstly, we cross-sectionally assessed HRQOL of 371 patients in Japan using the Bladder Cancer Index (BCI- Japanese). HRQOL of the four groups of patients (native bladder without intravesical therapy, native bladder with intravesical therapy, cystectomy with ileal conduit, and cystectomy with neobladder) were assessed. Secondly, we compared the Japanese with the American cohort (n = 315) from the original BCI paper. After adjusting for age and gender, the differences in each BCI subdomain score was analyzed.RESULTS: Among Japanese patients, the urinary domain function score was significantly lower among the cystectomy with neobladder group, compared to the cystectomy with ileal conduit group (p < 0. 01). Despite this, the urinary bother was comparable between the two groups. Although there were apparent differences between Japanese and American patients, there were few differences in Urinary and Bowel HRQOL. In three of the four treatment groups (other than native bladder with intravesical therapy), Japanese patients were more likely than Americans to report poor sexual function (p < 0.05). However, Japanese patients were less likely than Americans to be bothered by their lower sexual function, regardless of treatment (p <0.05).CONCLUSIONS: HRQOL outcomes following treatment of bladder cancer in Japan are comparable to those in the USA, except for sexual functioning and sexual bother. The BCI can be used for cross-cultural assessments of HRQOL in bladder cancer patients.

Health-related quality of life in Japanese patients with bladder cancer measured by a newly developed Japanese version of the Bladder Cancer Index.
Takahiro Osawa, John T Wei, Takashige Abe, Michitaka Honda, Shuhei Yamada, Jun Furumido, Hiroshi Kikuchi, Ryuji Matsumoto, Kazushi Hirakawa, Yasuyuki Sato, Yoshihiro Sasaki, Toru Harabayashi, Norikata Takada, Keita Minami, Hiroshi Tanaka, Ken Morita, Akira Kashiwagi, Naoto Miyajima, Tomoshige Akino, Sachiyo Murai, Yoichi M Ito, Shunichi Fukuhara, Katsuhiko Ogasawara, Nobuo Shinohara
International journal of clinical oncology, 25, 12, 2090, 2098, SPRINGER JAPAN KK, 2020年12月, ［国内誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: We validated a Japanese version of the Bladder Cancer Index (BCI) as a tool for measuring health-related quality of life (HRQOL) in bladder cancer patients treated with various surgical procedures. METHODS: The reliability and validity of the Japanese BCI were examined in 397 Japanese patients with bladder cancer via cross-sectional analysis. The patients simultaneously completed the Short Form (SF)-12, EQ-5D, and the Functional Assessment of Cancer Therapy-General and Bladder (FACT-G and FACT-BL). The differences in BCI subscales among various treatment groups were analyzed. RESULTS: This study involved 397 patients (301 males and 96 females), with a mean age of 70 years and a median disease duration of 29 months (IQR: 12-66 months). Of these patients, 221 underwent transurethral resection of a bladder tumor, and 176 patients underwent radical cystectomy (ileal conduit: 101 patients, ileal neobladder: 49, and ureterostomy: 26). Cronbach's alpha coefficient was ≥ 0.78 for all subscales, except the bowel bother subscale. Despite moderate correlations being detected between the function and bother score in urinary and bowel domains, the sexual function score was inversely correlated with the sexual bother score (r = - 0.19). A missing value percentage of > 15% was associated with old age (p < 0.05). The mean domain scores differed significantly among distinct clinically relevant treatment groups. CONCLUSIONS: Although revisions are needed to make it easier for elderly patients to comprehend, we confirmed the reliability and validity of the Japanese BCI. The Japanese BCI could be used for cross-cultural assessments of HRQOL in bladder cancer patients.

Quantitative analysis of treatments using real-time image gated spot-scanning with synchrotron-based proton beam therapy system log data.
Takaaki Yoshimura, Shinichi Shimizu, Takayuki Hashimoto, Kentaro Nishioka, Norio Katoh, Hiroshi Taguchi, Koichi Yasuda, Taeko Matsuura, Seishin Takao, Masaya Tamura, Sodai Tanaka, Yoichi M Ito, Yuto Matsuo, Hiroshi Tamura, Kenji Horita, Kikuo Umegaki, Hiroki Shirato
Journal of applied clinical medical physics, 21, 12, 10, 19, WILEY, 2020年12月, ［国際誌］
英語, 研究論文（学術雑誌）, A synchrotron-based real-time image gated spot-scanning proton beam therapy (RGPT) system with inserted fiducial markers can irradiate a moving tumor with high accuracy. As gated treatments increase the beam delivery time, this study aimed to investigate the frequency of intra-field adjustments corresponding to the baseline shift or drift and the beam delivery efficiency of a synchrotron-based RGPT system. Data from 118 patients corresponding to 127 treatment plans and 2810 sessions between October 2016 and March 2019 were collected. We quantitatively analyzed the proton beam delivery time, the difference between the ideal beam delivery time based on a simulated synchrotron magnetic excitation pattern and the actual treatment beam delivery time, frequency corresponding to the baseline shift or drift, and the gating efficiency of the synchrotron-based RGPT system according to the proton beam delivery machine log data. The mean actual beam delivery time was 7.1 min, and the simulated beam delivery time in an ideal environment with the same treatment plan was 2.9 min. The average difference between the actual and simulated beam delivery time per session was 4.3 min. The average frequency of intra-field adjustments corresponding to baseline shift or drift and beam delivery efficiency were 21.7% and 61.8%, respectively. Based on our clinical experience with a synchrotron-based RGPT system, we determined the frequency corresponding to baseline shift or drift and the beam delivery efficiency using the beam delivery machine log data. To maintain treatment accuracy within ± 2.0 mm, intra-field adjustments corresponding to baseline shift or drift were required in approximately 20% of cases. Further improvements in beam delivery efficiency may be realized by shortening the beam delivery time.

Resveratrol improves motor function in patients with muscular dystrophies: an open-label, single-arm, phase IIa study.
Kentaro Kawamura, Shinobu Fukumura, Koki Nikaido, Nobutada Tachi, Naoki Kozuka, Tsugumi Seino, Kingya Hatakeyama, Mitsuru Mori, Yoichi M Ito, Akiyoshi Takami, Shiro Hinotsu, Atsushi Kuno, Yukihiko Kawasaki, Yoshiyuki Horio, Hiroyuki Tsutsumi
Scientific reports, 10, 1, 20585, 20585, NATURE RESEARCH, 2020年11月25日, ［国際誌］
英語, 研究論文（学術雑誌）, Muscular dystrophies (MDs) are inherited disorders characterized by progressive muscle weakness. Previously, we have shown that resveratrol (3,5,4'-trihydroxy-trans-stilbene), an antioxidant and an activator of the protein deacetylase SIRT1, decreases muscular and cardiac oxidative damage and improves pathophysiological conditions in animal MD models. To determine whether resveratrol provides therapeutic benefits to patients with MDs, an open-label, single-arm, phase IIa trial of resveratrol was conducted in 11 patients with Duchenne, Becker or Fukuyama MD. The daily dose of resveratrol was 500 mg/day, which was increased every 8 weeks to 1000 and then 1500 mg/day. Primary outcomes were motor function, evaluated by a motor function measure (MFM) scale, muscular strength, monitored with quantitative muscle testing (QMT), and serum creatine kinase (CK) levels. Adverse effects and tolerability were evaluated as secondary outcomes. Despite the advanced medical conditions of the patients, the mean MFM scores increased significantly from 34.6 to 38.4 after 24 weeks of medication. A twofold increase was found in the mean QMT scores of scapula elevation and shoulder abduction. Mean CK levels decreased considerably by 34%. Diarrhoea and abdominal pain was noted in six and three patients, respectively. Resveratrol may provide some benefit to MD patients.

Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20-89 years: A cross-sectional nationwide study in Japan.
Keiko Yamada, Yoichi M Ito, Masao Akagi, Etsuo Chosa, Takeshi Fuji, Kenichi Hirano, Shinichi Ikeda, Hideaki Ishibashi, Yasuyuki Ishibashi, Muneaki Ishijima, Eiji Itoi, Norimasa Iwasaki, Ryoichi Izumida, Ken Kadoya, Masayuki Kamimura, Arihiko Kanaji, Hiroyuki Kato, Shunji Kishida, Naohiko Mashima, Shuichi Matsuda, Yasumoto Matsui, Toshiki Matsunaga, Naohisa Miyakoshi, Hiroshi Mizuta, Yutaka Nakamura, Ken Nakata, Go Omori, Koji Osuka, Yuji Uchio, Kazuteru Ryu, Nobuyuki Sasaki, Kimihito Sato, Masuo Senda, Akihiro Sudo, Naonobu Takahira, Hiroshi Tsumura, Satoshi Yamaguchi, Noriaki Yamamoto, Kozo Nakamura, Takashi Ohe
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 25, 6, 1084, 1092, ELSEVIER, 2020年11月, ［国内誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. METHODS: We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. RESULTS: The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. CONCLUSION: The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex.

Combination of minimum wiping pressure and number of wipings that can remove pseudo-skin dirt: A digital image color analysis.
Issei Konya, Inaho Shishido, Yoichi M Ito, Rika Yano
Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI), 26, 5, 639, 647, WILEY, 2020年09月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Excessive wiping friction in skin care may lead to skin damage. Bed baths are required to remove skin dirt without affecting the skin barrier function; the wiping pressure and number of wipings that satisfy these two requirements have not been clarified. This study aimed to determine the minimum wiping pressure and number of wipings that can remove skin dirt. MATERIALS AND METHODS: In this quasi-experimental study, 50 healthy adults received an adhesion of pseudo-oily and aqueous dirt, randomly assigned to the left and right forearms. Each participant was wiped three times with wiping pressure classified into six randomly assigned categories. The dirt removal rate was calculated by color-analyzing images captured before and after each wiping, and its dependence on the combination of wiping pressure and number of wipings was assessed using a linear mixed model. RESULTS: The combinations achieving oily dirt removal rates of 80% or more were wiping once and pressure ≥50 mmHg, wiping twice and pressure ≥40 mmHg, and wiping thrice and pressure ≥10 mmHg. Aqueous dirt was removed almost completely by wiping once, even with pressure ≥5 mmHg. CONCLUSION: Wiping with at least 10 mmHg or more three times can sufficiently remove both oily and aqueous dirt. Dirt removal rates with weak pressure can be made about as effective as those achieved with strong pressure by increasing the number of wipings. This result can be applied to daily nursing, home care, and long-term care health facilities.

Social participation patterns and the incidence of functional disability: The Japan Gerontological Evaluation Study.
Shigekazu Ukawa, Akiko Tamakoshi, Yutaka Okada, Yoichi M Ito, Rika Taniguchi, Yukako Tani, Yuri Sasaki, Junko Saito, Maho Haseda, Naoki Kondo, Katsunori Kondo
Geriatrics & gerontology international, 20, 8, 765, 772, WILEY, 2020年08月, ［国内誌］
英語, 研究論文（学術雑誌）, AIM: To examine whether patterns of social participation vary in their associations with functional disability. METHODS: Data from 44 978 participants (22 750 men and 22 228 women) who participated in the 2010 Japan Gerontological Evaluation Study were analyzed; a study of those aged ≥65 years from 23 municipalities in eight prefectures. Social participation information was obtained at baseline with an eight-item questionnaire. Incidence of functional disability from 2010 to 2013 was defined as a new certification of eligibility for municipal public long-term care insurance. Social participation patterns were analyzed using exploratory factor analysis and participants were classified into quartiles of factor scores of social participation patterns. A competing risk model was used to calculate the hazard ratios and 95% confidence intervals for the incidence of functional disability in 3 years of follow-up. RESULTS: Two social patterns were identified: sports groups/clubs and hobby groups, and political groups/organizations and industry/trade associations. For both patterns, compared with participants in the lowest quartile, participants in the highest quartile were more likely to be male, college educated, high-income and current drinkers. Both patterns were associated with reduced incidence of functional disability (adjusted hazard ratios for top quartile of sports and hobby pattern: 0.66, 95% confidence interval: 0.59, 0.74; for political and industry/trade pattern: 0.81, 95% confidence interval: 0.72, 0.90; P for trend <0.001 for both). CONCLUSIONS: Those whose social participation patterns were characterized by frequent participation in sports groups/clubs and hobby groups or political groups/organizations and industry/trade associations were less likely to develop a functional disability. Geriatr Gerontol Int 2020; 20: 765-772.

Right ventriculo-pulmonary arterial uncoupling and poor outcomes in pulmonary arterial hypertension
Toshitaka Nakaya, Hiroshi Ohira, Takahiro Sato, Taku Watanabe, Masaharu Nishimura, Noriko Oyama-Manabe, Masaru Kato, Yoichi M. Ito, Ichizo Tsujino
PULMONARY CIRCULATION, 10, 3, SAGE PUBLICATIONS INC, 2020年07月
英語, 研究論文（学術雑誌）, Right ventricular function critically affects the prognosis of patients with pulmonary arterial hypertension. We aimed to analyze the prognostic value of right ventricular indices calculated using magnetic resonance imaging and right heart catheterization metrics in pulmonary arterial hypertension. We retrospectively collected data from 57 Japanese patients with pulmonary arterial hypertension and 18 controls and calculated six indices of right ventricular function: two indices of contractility (end-systolic elastance calculated with right ventricular maximum pressure and with magnetic resonance imaging metrics); two indices of right ventricular-pulmonary arterial coupling (end-systolic elastance/arterial elastance calculated with the pressure method (end-systolic elastance/arterial elastance (P)) and with the volume method (end-systolic elastance/arterial elastance (V)); and two indices of right ventricular diastolic function (stiffness (beta) and end-diastolic elastance). We compared the indices between controls and patients with pulmonary arterial hypertension and examined their prognostic role. In patients with pulmonary arterial hypertension, end-systolic elastance (right ventricular maximum pressure) was higher (pulmonary arterial hypertension 0.94 (median) vs control 0.42 (mmHg/mL),p < 0.001), end-systolic elastance/arterial elastance (V) was lower (pulmonary arterial hypertension 0.72 vs control 1.69,p < 0.001), and beta and end-diastolic elastance were significantly higher than those in the controls. According to the log-rank test, end-systolic elastance/arterial elastance (P) and end-diastolic elastance were significantly associated with the composite event rate. According to the multivariate Cox regression analysis, decreased end-systolic elastance/arterial elastance (P) was associated with a higher composite event rate (hazard ratio 11.510, 95% confidence interval: 1.954-67.808). In conclusion, an increased right ventricular contractility, diastolic dysfunction, and a trend of impaired right ventricular-pulmonary arterial coupling were observed in our pulmonary arterial hypertension cohort. According to the multivariate outcome analysis, a decreased end-systolic elastance/arterial elastance (P), suggestive of impaired right ventricular-pulmonary arterial coupling, best predicted the pulmonary arterial hypertension-related event.

Oncological outcomes of a multicenter cohort treated with axitinib for metastatic renal cell carcinoma.
Takahiro Osawa, Takahiro Kojima, Tomohiko Hara, Mikio Sugimoto, Masatoshi Eto, Ario Takeuchi, Keita Minami, Yasutomo Nakai, Kosuke Ueda, Michinobu Ozawa, Motohide Uemura, Yasuyuki Miyauchi, Kojiro Ohba, Toshiro Suzuki, Satoshi Anai, Tetsuya Shindo, Naohisa Kusakabe, Keita Tamura, Motokiyo Komiyama, Takayuki Goto, Akira Yokomizo, Naoki Kohei, Akira Kashiwagi, Masaya Murakami, Tomokazu Sazuka, Hiroaki Yasumoto, Hideto Iwamoto, Koji Mitsuzuka, Daichi Morooka, Toru Shimazui, Yoshiaki Yamamoto, Suguru Ikeshiro, Hiroshi Nakagomi, Ken Morita, Ryotaro Tomida, Tango Mochizuki, Takamitsu Inoue, Hiroshi Kitamura, Shuhei Yamada, Yoichi M Ito, Sachiyo Murai, Hiroyuki Nishiyama, Nobuo Shinohara
Cancer science, 111, 7, 2460, 2471, WILEY, 2020年07月, ［国際誌］
英語, 研究論文（学術雑誌）, The present study aimed to evaluate the efficacy of the real-world use of axitinib and to develop a prognostic model for stratifying patients who could derive long-term benefit from axitinib. This was a retrospective, descriptive study evaluating the efficacy of axitinib in patients with metastatic renal cell carcinoma that had been treated with 1 or 2 systemic antiangiogenic therapy regimens at 1 of 36 hospitals belonging to the Japan Urologic Oncology Group between January 2012 and February 2019. The primary outcome was overall survival (OS). Using a split-sample method, candidate variables that exhibited significant relationships with OS were chosen to create a model. The new model was validated using the rest of the cohort. In total, 485 patients were enrolled. The median OS was 34 months in the entire study population, whereas it was not reached, 27 months, and 14 months in the favorable, intermediate, and poor risk groups, respectively, according to the new risk classification model. The following 4 variables were included in the final risk model: the disease stage at diagnosis, number of metastatic sites at the start of axitinib therapy, serum albumin level, and neutrophil : lymphocyte ratio. The adjusted area under the curve values of the new model at 12, 36, and 60 months were 0.77, 0.82, and 0.82, respectively. The efficacy of axitinib in routine practice is comparable or even superior to that reported previously. The patients in the new model's favorable risk group might derive a long-term survival benefit from axitinib treatment.

Prenatal exposure to 11 perfluoroalkyl substances and fetal growth: A large-scale, prospective birth cohort study.
Ikuko Kashino, Seiko Sasaki, Emiko Okada, Hideyuki Matsuura, Houman Goudarzi, Chihiro Miyashita, Eisaku Okada, Yoichi M Ito, Atsuko Araki, Reiko Kishi
Environment international, 136, 105355, 105355, PERGAMON-ELSEVIER SCIENCE LTD, 2020年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Prenatal maternal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) has been reportedly associated with decreased birth weight. Although a majority of epidemiological studies concerning perfluoroalkyl substances (PFAS) have focused on PFOS and PFOA, epidemiological studies of PFAS with longer carbon chains are scarce. In this study, we investigated whether prenatal maternal exposure to 11 PFAS, in particular those with longer carbon chains, is associated with fetal growth. METHODS: The study included 1985 mother-infant pairs (inclusive of preterm and post-term infants), who enrolled in a large-scale, prospective birth cohort study in any of the 37 hospitals in Hokkaido, Japan between 2003 and 2009. The concentration of 11 PFAS was measured in maternal plasma collected during the third trimester of pregnancy, using ultra-performance liquid chromatography in combination with triple quadrupole mass spectrometry. Associations between the measured PFAS values and weight, length, and head circumference of all newborns at birth were examined using multiple regression analyses with adjustment for potential confounders based on data collected from medical records, questionnaires, and those for maternal plasma samples. RESULTS: Of the 11 PFAS analyzed, prenatal perfluorononanoic acid (PFNA) [per log10-unit: regression coefficient (β) = -96.2 g, 95% confidence intervals (95% CI), -165.3 to -27.1] and perfluorodecanoic acid (PFDA) (β = -72.2 g, 95% CI, -138.1 to -6.3) concentrations were inversely associated with birth weight. Furthermore, PFNA concentrations were inversely associated with birth length (per Log10 unit: β = -0.48 cm, 95% CI; - 0.86 to -0.11). Maternal perfluorotridecanoic acid (PFTrDA) exposure showed a significant inverse association with birth weight only for female infants (per Log10 unit: β = -99.8 g, 95% CI, - 193.7 to -6.0) (P for interaction = 0.04). CONCLUSIONS: Our findings suggest that prenatal, maternal exposure to PFAS with longer carbon chains tends to be inversely associated with birth size of newborn infants, which may indicate that these commercially used compounds have an adverse effect on fetal growth.

Changes in cerebral oxygen saturation during one-lung ventilation determined using spatially resolved spectroscopy and contributing factors.
Nobuhiro Tanaka, Ryoko Ito Katoh, Masataka Yamamoto, Koji Hoshino, Yuji Morimoto, Yoichi M Ito, Tatsuya Kato
Journal of clinical anesthesia, 59, 99, 100, ELSEVIER SCIENCE INC, 2020年02月, ［査読有り］, ［国際誌］
英語

Single-Center Noninferiority Randomized Trial on the Efficacy and Safety of Low- and High-Dose Rush Oral Milk Immunotherapy for Severe Milk Allergy.
Yuri Takaoka, Yuko Yajima, Yoichi M Ito, Junko Kumon, Takahiro Muroya, Yuki Tsurinaga, Amane Shigekawa, Shinichi Takahashi, Norihito Iba, Taisuke Tsuji, Tomoki Nishikido, Yukinori Yoshida, Satoru Doi, Makoto Kameda
International archives of allergy and immunology, 181, 9, 699, 705, KARGER, 2020年, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Oral immunotherapy (OIT) has been reported to be effective but associated with a risk of severe symptoms. Thus, an OIT method with decreased risk is required. OBJECTIVES: We aimed to evaluate the efficacy and safety of low- and high-dose OIT regimens in children with severe milk allergy. METHODS: Overall, 33 participants (median age, 9 years; median final dose of the milk oral food challenge [OFC], 2 mL) were included. The participants were randomly assigned to groups that received either a low (20 mL; n = 19) or high (100 mL; n = 14) maintenance target dose of OIT. The dose was gradually increased to the target dose in the rush escalation phase and was then maintained daily at home. The primary endpoint was the final OFC dose at 6 months of OIT. Adverse events during OIT were evaluated. RESULTS: The final OFC dose after OIT was significantly higher than that before OIT in both groups (low-dose, p = 0.000; high-dose, p = 0.006), but there was no significant difference in the final OFC dose between the 2 groups (p = 0.767). In the maintenance phase, the high-dose group had significantly more severe symptoms than did the low-dose group (0.5%, 11/2,355 total intake events vs. 0.1%, 4/3,230 total intake events; p = 0.018). CONCLUSIONS: An equally increased dose effect was observed for maintenance OIT doses of 20 and 100 mL in children with severe milk allergy. The risk of severe symptoms in the maintenance phase was lower in the low-dose group. A low-dose OIT regimen is recommended for severe milk allergy.

The urethral position may shift due to urethral catheter placement in the treatment planning for prostate radiation therapy.
Yasuhiro Dekura, Kentaro Nishioka, Takayuki Hashimoto, Naoki Miyamoto, Ryusuke Suzuki, Takaaki Yoshimura, Ryuji Matsumoto, Takahiro Osawa, Takashige Abe, Yoichi M Ito, Nobuo Shinohara, Hiroki Shirato, Shinichi Shimizu
Radiation oncology (London, England), 14, 1, 226, 226, BMC, 2019年12月12日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: To determine the best method to contour the planning organ at risk volume (PRV) for the urethra, this study aimed to investigate the displacement of a Foley catheter in the urethra with a soft and thin guide-wire. METHODS: For each patient, the study used two sets of computed tomography (CT) images for radiation treatment planning (RT-CT): (1) set with a Foley urethral catheter (4.0 mm diameter) plus a guide-wire (0.46 mm diameter) in the first RT-CT and (2) set with a guide-wire alone in the second CT recorded 2 min after the first RT-CT. Using three fiducial markers in the prostate for image fusion, the displacement between the catheter and the guide-wire in the prostatic urethra was calculated. In 155 consecutive patients treated between 2011 and 2017, 5531 slices of RT-CT were evaluated. RESULTS: Assuming that ≥3.0 mm of difference between the catheter and the guide-wire position was a significant displacement, the urethra with the catheter was displaced significantly from the urethra with the guide-wire alone in > 20% of the RT-CT slices in 23.2% (36/155) of the patients. The number of patients who showed ≥3.0 mm anterior displacement with the catheter in ≥20% RT-CT slices was significantly larger at the superior segment (38/155) than at the middle (14/155) and inferior segments (18/155) of the prostatic urethra (p < 0.0167). CONCLUSIONS: The urethral position with a Foley catheter is different from the urethral position with a thin and soft guide-wire in a significant proportion of the patients. This should be taken into account for the PRV of the urethra to ensure precise radiotherapy such as in urethra-sparing radiotherapy.

The development of the preoperative nomogram predicting major perioperative complications after radical cystectomy with ileal conduit or orthotopic neobladder
Shuhei Yamada, Takahiro Osawa, Takashige Abe, Norikata Takada, Ryuji Matsumoto, Yoichi M. Ito, Hiroshi Kikuchi, Naoto Miyajima, Kunihiko Tsuchiya, Satoru Maruyama, Sachiyo Murai, Nobuo Shinohara
Acta Urologica Japonica, 65, 12, 495, 499, Editorial Board of Acta Urologica Japonica, 2019年12月01日
日本語, 研究論文（学術雑誌）, Radical cystectomy (RG) is the gold standard for managing muscle-invasive and high-risk non-muscle-invasive bladder cancer, but is accompanied by non-negligible operative risk. The aim of this study is to identify preoperative variables to predict major perioperative complications after RC and to develop a nomogram using the cohort from multiple institutions in Japan. We retrospectively reviewed 668 patients who underwent open RC with ileal conduit or neobladder at Hokkaido University hospital and 20 affiliated institutions between 1997 and 2010. Complications occurring within 90 days of surgery were graded using modified Clavien classification system. We defined modified Clavien grade 3 or more as major complications and performed univariate and multivariate logistic regression analyses. Predictive accuracy of the nomogram was evaluated with the area under the receiver operating characteristics curve (AUC). A total of 528 men and 140 women were included in this study. There were a total of 160/668 patients (24%) with major perioperative complications. A multivariate model identified gender (OR: 1.63, p = 0.04), cardiovascular comorbidity (OR: 1.48, p = 0.03) and simultaneous nephroureterectomy (OR: 2.81, p = 0. 01) as independent predictors. Using these 3 variables, a nomogram was developed with the AUC of 0.58. Predictive performance of our nomogram showed only fair performance
but at least, we identified male, cardiovascular comorbidity and simultaneous nephroureterectomy as independent predictors of perioperative major complications.

腸管利用尿路変向を行った開腹膀胱全摘除術における術前因子を用いた周術期重度合併症予測ノモグラムの作成の試み
山田 修平, 大澤 崇宏, 安部 崇重, 高田 徳容, 松本 隆児, 伊藤 陽一, 菊地 央, 宮島 直人, 土屋 邦彦, 丸山 覚, 村井 祥代, 篠原 信雄
泌尿器科紀要, 65, 12, 495, 499, 泌尿器科紀要刊行会, 2019年12月
日本語, 1997〜2010年までの間に20施設で膀胱癌に対して腸管利用尿路変向の開腹膀胱全摘除術(開腹RC)を施行した668例(男性528例、女性140例、年齢中央値65歳)を対象に、周術期重度合併症の術前予測因子を検討した。その結果、男性、心血管疾患既往、同時NUx(同時腎尿管全摘除術)が周術期重度合併症の有意な予測因子となったものの、この3つの因子を用いたモノグラムではAUC 0.58と十分な予測精度を持つには至らなかった。

Analysis of treatment process time for real-time-image gated-spot-scanning proton-beam therapy (RGPT) system.
Yoshimura T, Shimizu S, Hashimoto T, Nishioka K, Katoh N, Inoue T, Taguchi H, Yasuda K, Matsuura T, Takao S, Tamura M, Ito YM, Matsuo Y, Tamura H, Horita K, Umegaki K, Shirato H
Journal of applied clinical medical physics, 21, 2, 38, 49, WILEY, 2019年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, We developed a synchrotron-based real-time-image gated-spot-scanning proton-beam therapy (RGPT) system and utilized it to clinically operate on moving tumors in the liver, pancreas, lung, and prostate. When the spot-scanning technique is linked to gating, the beam delivery time with gating can increase, compared to that without gating. We aim to clarify whether the total treatment process can be performed within approximately 30 min (the general time per session in several proton therapy facilities), even for gated-spot-scanning proton-beam delivery with implanted fiducial markers. Data from 152 patients, corresponding to 201 treatment plans and 3577 sessions executed from October 2016 to June 2018, were included in this study. To estimate the treatment process time, we utilized data from proton beam delivery logs during the treatment for each patient. We retrieved data, such as the disease site, total target volume, field size at the isocenter, and the number of layers and spots for each field, from the treatment plans. We quantitatively analyzed the treatment process, which includes the patient load (or setup), bone matching, marker matching, beam delivery, patient unload, and equipment setup, using the data obtained from the log data. Among all the cases, 90 patients used the RGPT system (liver: n = 34; pancreas: n = 5; lung: n = 4; and prostate: n = 47). The mean and standard deviation (SD) of the total treatment process time for the RGPT system was 30.3 ± 7.4 min, while it was 25.9 ± 7.5 min for those without gating treatment, excluding craniospinal irradiation (CSI; head and neck: n = 16, pediatric: n = 31, others: n = 15); for CSI (n = 11) with two or three isocenters, the process time was 59.9 ± 13.9 min. Our results demonstrate that spot-scanning proton therapy with a gating function can be achieved in approximately 30-min time slots.

Randomized phase II trial of survivin 2B peptide vaccination for patients with HLA-A24-positive pancreatic adenocarcinoma.
Hiroaki Shima, Giichiro Tsurita, Satoshi Wada, Yoshihiko Hirohashi, Hiroshi Yasui, Hiroshi Hayashi, Takashi Miyakoshi, Kazue Watanabe, Aiko Murai, Hiroko Asanuma, Serina Tokita, Terufumi Kubo, Munehide Nakatsugawa, Takayuki Kanaseki, Tomohide Tsukahara, Yutaka Nakae, Osamu Sugita, Yoichi M Ito, Yasunori Ota, Yasutoshi Kimura, Goro Kutomi, Koichi Hirata, Toru Mizuguchi, Kohzoh Imai, Ichiro Takemasa, Noriyuki Sato, Toshihiko Torigoe
Cancer science, 110, 8, 2378, 2385, WILEY, 2019年08月, ［国際誌］
英語, 研究論文（学術雑誌）, The prognosis of advanced pancreatic adenocarcinoma is still extremely poor. This study sought to determine the efficacy of, and immunological response to, peptide vaccination therapy in patients with this disease. In this multicenter randomized phase II study, patients with advanced pancreatic adenocarcinoma after gemcitabine and/or tegafur/gimeracil/oteracil were randomly assigned to 3 groups that each received a 2-step treatment course. In Step 1, the groups received treatments of: (i) survivin 2B peptide (SVN-2B) plus interferon-β (IFNβ); (ii) SVN-2B only; or (iii) placebo until the patients show progression. In Step 2, all patients who consented to participate received 4 treatments with SVN-2B plus IFNβ. The primary endpoint was progression-free survival (PFS) after initiation of Step 1 treatment. Secondary endpoints included immunological effects assessed by analysis of PBMCs after Step 1. Eighty-three patients were randomly assigned to receive SVN-2B plus IFNβ (n = 30), SVN-2B (n = 34), or placebo (n = 19). No significant improvement in PFS was observed. Survivin 2B-specific CTLs were found to be increased in the SVN-2B plus IFNβ group by tetramer assay. Among patients who participated in Step 2, those who had received SVN-2B plus IFNβ in Step 1 showed better overall survival compared with those who had received placebo in Step 1. Patients vaccinated with SVN-2B plus IFNβ did not have improved PFS, but showed significant immunological reaction after vaccination. Subgroup analysis suggested that a longer SVN-2B plus IFNβ vaccination protocol might confer survival benefit. (Clinical trial registration number: UMIN 000012146).

Effects of femoral bone defect morphology on initial polished tapered stem stability in massive defect model: a biomechanical study.
Tohru Irie, Daisuke Takahashi, Tsuyoshi Asano, Tomohiro Shimizu, Ryuta Arai, Alaa Muhammad Terkawi, Yoichi M Ito, Norimasa Iwasaki
BMC musculoskeletal disorders, 20, 1, 355, 355, BMC, 2019年08月01日, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Good outcomes have been reported in revision total hip replacement with massive segmental defects using impaction bone grafting with circumferential metal meshes. However, the morphology of defects that require a mesh is poorly defined. The purpose of this study was to evaluate the effects of a variety of segmental defects on load transmission to the proximal femur under both axial and rotational loads. METHODS: Initial stability of the Exeter stem was investigated in a composite bone model using three medial bone defect morphologies: Long (length 5 cm × width 2 cm), Short (2.5 cm × 2 cm), Square (3.2 cm × 3.2 cm), Square with mesh (3.2 cm × 3.2 cm defect covered with metal mesh), and with no defect as control. Specimens (5 per group) were axially loaded and internally rotated up to 20° or to failure. Strain distributions of the femora were measured using a strain gauge. RESULTS: All Square group specimens failed while rotation was increasing. In the other four groups, failure was not observed in any specimens. Mean torsional stiffness in the Long (4.4 ± 0.3 Nm/deg.) and Square groups (4.3 ± 0.3 Nm/deg.) was significantly smaller than in the Control group (4.8 ± 0.3 Nm/deg.). In the medio-cranial region, the magnitude of the maximum principal strain in the Square group (1176.4 ± 100.9) was significantly the largest (Control, 373.2 ± 129.5, p < 0.001; Long, 883.7 ± 153.3, p = 0.027; Short, 434.5 ± 196.8, p < 0.001; Square with mesh, 256.9 ± 100.8, p < 0.001). Torsional stiffness, and both maximum and minimum principal strains in the Short group showed no difference compared to the Control group in any region. CONCLUSIONS: Bone defect morphology greatly affected initial stem stability and load transmission. If defect morphology is not wide and the distal end is above the lower end of the lesser trochanter, it may be acceptable to fill the bone defect region with bone cement. However, this procedure is not acceptable for defects extending distally below the lower end of the lesser trochanter or defects 3 cm or more in width.

Impact of organ motion on volumetric and dosimetric parameters in stomach lymphomas treated with intensity-modulated radiotherapy.
Uchinami Y, Suzuki R, Katoh N, Taguchi H, Yasuda K, Miyamoto N, Ito YM, Shimizu S, Shirato H
Journal of applied clinical medical physics, 20, 8, 78, 86, WILEY, 2019年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: Interplay effects may influence dose distributions to a moving target when using dynamic delivery techniques such as intensity-modulated radiotherapy (IMRT). The aim of this study was to evaluate the impact of organ motion on volumetric and dosimetric parameters in stomach lymphomas treated with IMRT. METHODS: Ten patients who had been treated with IMRT for stomach lymphomas were enrolled. The clinical target volume (CTV) was contoured as the whole stomach. Considering interfractional uncertainty, the internal target volume (ITV) margin was uniformly 1.5 cm to the CTV and then modified based on the 4DCT images in case of the large respiratory motion. The planning target volume (PTV) was created by adding 5 mm to the ITV. The impact of organ motion on the volumetric and dosimetric parameters was evaluated retrospectively (4D simulation). The organ motion was reproduced by shifting the isocenter on the radiation treatment planning system. Several simulation plans were created to test the influence of the beam-on timing in the respiration cycle on the dose distribution. The homogeneity index (HI), volume percentage of stomach covered by the prescribed dose (Vp ), and D99 of the CTV were evaluated. RESULTS: The organ motion was the largest in the superior-inferior direction (10.1 ± 4.5 mm [average ± SD]). Stomach volume in each respiratory phase compared to the mean volume varied approximately within a ± 5% range in most of the patients. The PTV margin was sufficiently large to cover the CTV during the IMRT. There was a significant reduction in Vp and D99 but not in HI in the 4D simulation in free-breathing and multiple fractions compared to the clinically-used plan (P < 0.05) suggesting that interplay effects deteriorate the dose distribution. The absolute difference of D99 was less than 1% of the prescribed dose. CONCLUSIONS: There were significant interplay effects affecting the dose distribution in stomach IMRT. The magnitude of the dose reduction was small when patients were treated on free-breathing and multiple fractions.

Safety and efficacy of amnion-derived mesenchymal stem cells (AM01) in patients with steroid-refractory acute graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: a study protocol for a phase I/II Japanese trial.
Kenichi Yamahara, Akiko Hamada, Toshihiro Soma, Rika Okamoto, Masaya Okada, Satoshi Yoshihara, Kyoko Yoshihara, Kazuhiro Ikegame, Hiroya Tamaki, Katsuji Kaida, Takayuki Inoue, Yuko Ohsugi, Hiroki Nishikawa, Hiroshi Hayashi, Yoichi M Ito, Hiroaki Iijima, Shunsuke Ohnishi, Daigo Hashimoto, Toshiyuki Isoe, Takanori Teshima, Hiroyasu Ogawa, Norihiro Sato, Yoshihiro Fujimori
BMJ open, 9, 7, e026403, BMJ PUBLISHING GROUP, 2019年07月09日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: Regenerative medicine and cell therapies have been gaining much attention among clinicians. Therapeutic infusion of mesenchymal stromal cells (MSCs) is now a leading investigational strategy for the treatment of acute graft-versus-host disease (aGVHD). Bone marrow MSCs are approved for manufacture and marketing as a cell therapy for aGVHD. Our non-clinical studies confirmed that human amnion-derived MSCs had immunomodulatory activity equal to or higher than that of human bone marrow MSCs. This study will aim to evaluate the safety and efficacy of amnion-derived MSCs (AM01) in patients with steroid-refractory aGVHD. METHODS AND ANALYSIS: This study will be a multicentre, single-arm, open-label trial (an interventional study). This clinical trial will begin with a low-dose group, and when safety has been confirmed in at least three cases in the low-dose group, treatment will begin for the high-dose group, for which the safety will also be verified. The primary endpoint is to assess the safety of intravenous infusion therapy of AM01 within 24 hours after intravenous infusion of AM01. The secondary endpoint is to explore the efficacy of intravenous infusion therapy with AM01. ETHICS AND DISSEMINATION: The institutional review boards of all participating hospitals approved this study protocol (latest V3.3.0, 3 August 2018). Final data will be publicly announced. A report releasing the study results will be submitted for publication to an appropriate peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000029945.

Three-dimensional depth sensor imaging to identify adolescent idiopathic scoliosis: a prospective multicenter cohort study.
Terufumi Kokabu, Noriaki Kawakami, Koki Uno, Toshiaki Kotani, Teppei Suzuki, Yuichiro Abe, Kenichiro Maeda, Fujio Inage, Yoichi M Ito, Norimasa Iwasaki, Hideki Sudo
Scientific reports, 9, 1, 9678, 9678, NATURE PUBLISHING GROUP, 2019年07月04日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Adolescent idiopathic scoliosis is the most ordinary pediatric spinal disease that causes a three-dimensional deformity. Early detection of this potentially progressive deformity is considered crucial. The purpose of the present study was to report the potential for accurately diagnosis of adolescent idiopathic scoliosis using a newly developed, automated, noninvasive asymmetry-recognition system for the surface of the human back using a three-dimensional depth sensor. We included 170 subjects with suspected adolescent idiopathic scoliosis in this study. Outcomes measured included patient demographics, Cobbe angles from radiographic measurements, and asymmetry indexes. The coefficient of correlation between the asymmetry index and the Cobb angle was 0.85. For the prediction of scoliosis >10°, the area under the curve was 0.98, sensitivity was 0.97, specificity was 0.93, positive predictive value was 0.99, negative predictive value was 0.72, accuracy was 0.97, positive likelihood ratio was 13.55, and negative likelihood ratio was 0.04. The posterior test probability for the positive screen >10° was 98.9% if the asymmetry index was >1.268, three times in a row. This novel system automatically evaluated the back asymmetry. Therefore, this study demonstrates the outstanding discriminative ability of this newly developed system for deciding whether an examinee should undergo additional radiography to define scoliosis. This system can be used as an alternative to the forward bend test and scoliometer measurement in clinics. Future studies should seek to confirm these findings in a larger group and involve mass school scoliosis screening programs within the context of a multicenter trial.

cT1腎癌に対する開腹腎部分切除術と鏡視下腎部分切除術後のSF-36を用いたQOLの比較
大澤 崇宏, 安部 崇重, 菊地 央, 松本 隆児, 宮島 直人, 土屋 邦彦, 丸山 覚, 伊藤 陽一, 村井 祥代, 篠原 信雄
泌尿器外科, 32, 7, 985, 986, 医学図書出版(株), 2019年07月
日本語

Bladder Cancer Index(BCI)日本語版の妥当性検証
古御堂 純, 大澤 崇宏, 伊藤 陽一, 菊地 央, 松本 隆児, 平川 和志, 佐藤 泰之, 佐々木 芳浩, 高田 徳容, 原林 透, 柏木 明, 田中 博, 三浪 圭太, 森田 研, 山田 修平, 村井 祥代, 安部 崇重, 篠原 信雄
泌尿器外科, 32, 7, 991, 991, 医学図書出版(株), 2019年07月
日本語

Phase II study of trastuzumab and docetaxel therapy in patients with HER2-positive recurrent and/or metastatic salivary gland carcinoma
Ichiro Kinoshita, Satoshi Kano, Yasushi Shimizu, Naomi Kiyota, Yuichiro Tada, Kei Ijichi, Tmoko Yamazaki, Akihiro Homma, Yoichi M. Ito, Kota Ono, Keiko Kobayashi, Toshiyuki Isoe, Yutaka Hatanaka, Hitoshi Tsuda, Shojiroh Morinaga, Yoshihiro Matsuno, Hirotoshi Dosaka-Akita
CANCER RESEARCH, 79, 13, AMER ASSOC CANCER RESEARCH, 2019年07月
英語

Three-dimensional depth sensor imaging to identify adolescent idiopathic scoliosis: a prospective multicenter cohort study　　　　　　　　　　　　　　　
Terufumi Kokabu, Noriaki Kawakami, Koki Uno, Toshiaki Kotani, Teppei Suzuki, Yuichiro Abe, Kenichiro Maeda, Fujio Inage, Yoichi M. Ito, Norimasa Iwasaki, Hideki Sudo
Scientific Reports, 9, 9678, 1, 8, 2019年07月, ［査読有り］
英語, 研究論文（学術雑誌）

The normal tissue complication probability model-based approach considering uncertainties for the selective use of radiation modality in primary liver cancer patients.
Prayongrat A, Kobashi K, Ito YM, Katoh N, Tamura M, Dekura Y, Toramatsu C, Khorprasert C, Amornwichet N, Alisanant P, Shirato H, Shimizu S
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology, 135, 100, 106, ELSEVIER IRELAND LTD, 2019年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: To predict the probability of radiation-induced liver toxicity (RILT) and implement the normal tissue complication probability (NTCP) model-based approach considering confidence intervals (CIs) to select patients for new treatment techniques, such as proton beam therapy, based on a certain NTCP reduction (ΔNTCP) threshold for primary liver cancer patients. METHODS AND MATERIALS: Common Toxicity Criteria for Adverse Events (CTCAE) grade ≥2 RILT was scored. The Lyman NTCP models predicting the probability of CTCAE grade ≥2 RILT as a function of the fraction-size adjusted mean liver dose (MLD), using reference fraction size = 2 Gy/fraction and α/β ratio = 2 Gy, were fitted using the maximum likelihood method. At certain combinations of MLDs, ΔNTCP with a CI was evaluated by the delta method. RESULTS: Of the 239 patients, the incidence of CTCAE grade ≥2 RILT was 55% (46% in the Child-Pugh (CP)-A vs. 81% in the CP-B/C, p < 0.001). Among 180 CP-A patients, 40% who had viral hepatitis infections experienced toxicity vs. 32% in the nonhepatitis subgroup. The MLD was 18 Gy in the toxicity group vs. 16.1 Gy in the nontoxicity group (p = 0.002). The estimated NTCP model parameters specific to the patient subgroups and the ΔNTCP with CI assuming a particular CP classification and viral hepatitis infection status were considerably different which possible changed treatment decision. CONCLUSIONS: Patients with CP-A and viral hepatitis infection or CP-B/C cirrhosis had greater susceptibility to CTCAE grade ≥2 RILT. The estimated NTCP and ΔNTCP for individual patients along with a consideration of uncertainties improve the reliability of the NTCP model-based approach.

Verification of the effectiveness of fucosylated haptoglobin as a pancreatic cancer marker in clinical diagnosis.
Kuwatani M, Kawakami H, Kubota Y, Kawakubo K, Ito YM, Togo S, Ikeda T, Kusama K, Kobayashi Y, Murata T, Sakamoto N
Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 19, 4, 569, 577, ELSEVIER, 2019年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL) that had specificity for fucose α1-6 was reported as an effective biomarker for several gastrointestinal diseases. The aim of this study was to verify Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL-HP) as a pancreatic cancer (PC) marker using a new method of PhoSL-ELISA. METHODS: PhoSL-HP in sera from 98 PC patients and 158 non-PC samples including 32 intraductal papillary mucinous neoplasm (IPMN) patients, 21 chronic pancreatitis (CP) patients and 105 non-pancreatic disease controls (NPDC) were measured. We compared sensitivities, specificities and areas under the curves (AUC) of PhoSL-HP, CA19-9 and CEA as single markers. We also evaluated PhoSL-HP as combination marker by comparing AUC of CA19-9 combined with PhoSL-HP or CEA. RESULTS: The sensitivities of PhoSL-HP, CA19-9 and CEA for PC were 58%, 76% and 42%, respectively. Although the specificity of PhoSL-HP for NPDC was inferior to both of CA19-9 and CEA, that for pancreatic diseases was higher than both of CA19-9 and CEA. Combined CA19-9 with PhoSL-HP, the AUC was significantly higher at 0.880 than single use of CA19-9 at 0.825 in case of distinguishing PC from other pancreatic diseases. In contrast, the AUC of CA19-9 was not elevated significantly when combined with CEA. CONCLUSION: PhoSL-HP would be a useful marker for PC and have sufficient complementarity for CA19-9.

Bladder Cancer Index(BCI)日本語版の開発におけるPilot Study
大澤 崇宏, Wei John T., 伊藤 陽一, 成田 学, 賀古 勇輝, 宮田 遙, 菊地 央, 松本 隆児, 宮島 直人, 丸山 覚, 安部 崇重, 村井 祥代, 篠原 信雄
泌尿器外科, 32, 5, 518, 518, 医学図書出版(株), 2019年05月
日本語

Clinical experience of craniospinal intensity-modulated spot-scanning proton therapy using large fields for central nervous system medulloblastomas and germ cell tumors in children, adolescents, and young adults.
Hashimoto T, Shimizu S, Takao S, Terasaka S, Iguchi A, Kobayashi H, Mori T, Yoshimura T, Matsuo Y, Tamura M, Matsuura T, Ito YM, Onimaru R, Shirato H
Journal of radiation research, 60, 4, 527, 537, OXFORD UNIV PRESS, 2019年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The outcomes of intensity-modulated proton craniospinal irradiation (ipCSI) are unclear. We evaluated the clinical benefit of our newly developed ipCSI system that incorporates two gantry-mounted orthogonal online X-ray imagers with a robotic six-degrees-of-freedom patient table. Nine patients (7-19 years old) were treated with ipCSI. The prescribed dose for CSI ranged from 23.4 to 36.0 Gy (relative biological effectiveness) in 13-20 fractions. Four adolescent and young adult (AYA) patients (15 years or older) were treated with vertebral-body-sparing ipCSI (VBSipCSI). Myelosuppression following VBSipCSI was compared with that of eight AYA patients treated with photon CSI at the same institution previously. The mean homogeneity index (HI) in the nine patients was 0.056 (95% confidence interval: 0.044-0.068). The mean time from the start to the end of all beam delivery was 37 min 39 s ± 2 min 24 s (minimum to maximum: 22 min 49 s - 42 min 51 s). The nadir white blood cell, hemoglobin, and platelet levels during the 4 weeks following the end of the CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0071, 0.0453, 0.0024, respectively). The levels at 4 weeks after the end of CSI were significantly higher in the VBSipCSI group than in the photon CSI group (P = 0.0023, 0.0414, 0.0061). Image-guided ipCSI was deliverable in a reasonable time with sufficient HI. Using VBSipCSI, AYA patients experienced a lower incidence of serious acute hematological toxicity than AYA patients treated with photon CSI.

Magnetic resonance imaging T1 and T2 mapping provide complementary information on the bone mineral density regarding cancellous bone strength in the femoral head of postmenopausal women with osteoarthritis.
Endo K, Takahata M, Sugimori H, Yamada S, Tadano S, Wang J, Todoh M, Ito YM, Takahashi D, Kudo K, Iwasaki N
Clinical biomechanics (Bristol, Avon), 65, 13, 18, ELSEVIER SCI LTD, 2019年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Since bone mass is not the only determinant of bone strength, there has been increasing interest in incorporating the bone quality into fracture risk assessments. We aimed to examine whether the magnetic resonance imaging (MRI) T1 or T2 mapping value could provide information that is complementary to bone mineral density for more accurate prediction of cancellous bone strength. METHODS: Four postmenopausal women with hip osteoarthritis underwent 3.0-T MRI to acquire the T1 and T2 values of the cancellous bone of the femoral head before total hip arthroplasty. After the surgery, the excised femoral head was portioned into multiple cubic cancellous bone specimens with side of 5 mm, and the specimens were then subjected to microcomputed tomography followed by biomechanical testing. FINDINGS: The T1 value positively correlated with the yield stress (σy) and collapsed stress (σc). The T2 value did not correlate with the yield stress, but it correlated with the collapsed stress and strength reduction ratio (σc/σy), which reflects the progressive re-fracture risk. Partial correlation coefficient analyses, after adjusting for the bone mineral density, showed a statistically significant correlation between T1 value and yield stress. The use of multiple coefficients of determination by least squares analysis emphasizes the superiority of combining the bone mineral density and the MRI mapping values in predicting the cancellous bone strength compared with the bone mineral density-based prediction alone. INTERPRETATION: The MRI T1 and T2 values predict cancellous bone strength including the change in bone quality.

The responsiveness of triaxial accelerometer measurement of gait ataxia is higher than that of the Scale for the Assessment and Rating of Ataxia in the early stages of spinocerebellar ataxia
Shirai S, Yabe I, Takahashi-Iwata I, Matsushima M, Ito YM, Takakusaki K, Sasaki H
Cerebellum, 18, 4, 721, 730, SPRINGER, 2019年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, We reported previously that the average medial-lateral gait amplitude while walking on a straight path determined using triaxial accelerometers fixed on the middle of the upper back may be a quantitative and concise indicator for the severity of cerebellar ataxia. Considering that gait ataxia is a typical initial symptom in a variety of spinocerebellar degeneration (SCD), we aimed to develop quantitative biomarkers for cerebellar ataxia as metric variables. We used triaxial accelerometers to analyze gait parameters in 14 patients with SCD at 3 points over 3 years (at baseline, 1.5 years and 3 years). Analysis of covariance (ANCOVA) models adjusted for the baseline scores were used to estimate sample sizes. The mean medial-lateral amplitude (ML) gained by a triaxial accelerometer fixed on upper back could detect the each 1.5-year change. In the 14 patients, the mean ML(m) was 0.032 ± 0.007(SD) at entry, 0.037 ± 0.008 after 1.5-year follow, and 0.042 ± 0.020 after 3-year follow. In contrast, SARA gait scores were 2.9, 2.9, and 3.0, respectively. The responsiveness of the quantitative evaluation of gait ataxia by triaxial accelerometers is higher than that of the SARA within a 1.5-year follow-up period. Gait analysis by triaxial accelerometers will be complementary to the evaluation of scales like SARA in the assessment of clinical severity of SCD patients in early stage.

Identifying the Essential Portions of the Skill Acquisition Process Using Item Response Theory.
Poudel S, Watanabe Y, Kurashima Y, Ito YM, Murakami Y, Tanaka K, Kawase H, Shichinohe T, Hirano S
Journal of surgical education, 76, 4, 1101, 1106, ELSEVIER SCIENCE INC, 2019年02月, ［査読有り］
英語, 研究論文（学術雑誌）, OBJECTIVE: Item response theory (IRT) was originally developed to make performance assessments more accurate. However, IRT analysis of the intraoperative performance of surgical trainees could help identify the elements that the trainees find difficult during the skill acquisition process. The aim of this study was to identify the essential portions of the skill acquisition process of a surgical procedure using the IRT.DESIGN: The 24-item assessment checklist was used to evaluate a recorded intra-operative performance of a laparoscopic inguinal hernia repair. The scores were analyzed using IRT to calculate the difficulty and discrimination level of each item.SETTING: Fifteen institutes.PARTICIPANTS: Thirty surgical trainees.RESULTS: A total of 123 assessments were analyzed. The item analysis showed the procedure specific item "traction of peritoneum (difficulty: -0.45; discrimination: 19.37)" and generic items "instrument handling (difficulty: -0.59; discrimination: 3.82)" and "flow of procedure (difficulty: 0.09; discrimination: 3.27)" to be key elements in the skill acquisition process of the procedure.CONCLUSIONS: Key elements in the skill acquisition process of the procedure were quantitatively identified by applying the IRT analysis. This could lead to the use of IRT in designing and developing a more effective training curriculum. ((C) 2019 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Progressive left ventricular dysfunction and myocardial fibrosis in Duchenne and Becker muscular dystrophy: a longitudinal cardiovascular magnetic resonance study.
Tadao Aikawa, Atsuhito Takeda, Noriko Oyama-Manabe, Masanao Naya, Hirokuni Yamazawa, Kazuhiro Koyanagawa, Yoichi M Ito, Toshihisa Anzai
Pediatric cardiology, 40, 2, 384, 392, SPRINGER, 2019年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, This study examined the progression of left ventricular dysfunction and myocardial fibrosis in patients with Duchenne muscular dystrophy (DMD) or Becker muscular dystrophy (BMD) to evaluate the effects of angiotensin-converting enzyme inhibitor (ACEI). Ninety-eight cardiovascular magnetic resonance (CMR) studies in 34 consecutive patients with DMD (n = 21) or BMD (n = 13) were retrospectively reviewed. Left ventricular ejection fraction (LVEF) and the extent of myocardial late gadolinium enhancement (LGE) were semiautomatically quantified. During the study period, five patients had already been treated with ACEI at the first CMR; five were started on ACEI at LVEF ≥ 55% and 10 at LVEF < 55%. All patients had hyperenhanced myocardium on LGE images at the first CMR (median extent, 3.3%; interquartile range 0.1-14.3%). A mixed-effects model for longitudinal data of each patient, adjusted for age, type of muscular dystrophy, steroid use, and ACEI use showed that higher age (β = - 1.1%/year; 95% confidence interval [CI], - 1.8% to - 0.4%; p = 0.005) and no use of ACEI (β = - 3.1%; 95% CI, - 5.4% to - 0.8%; p = 0.009) were significantly associated with a lower LVEF. When ACEI use was stratified by time of initiation (LVEF ≥ 55% vs. < 55%), only ACEI initiation at LVEF < 55% had a beneficial effect on LVEF at each imaging examination (β = 3.7%; 95% CI, 0.9-6.4%; p = 0.010). ACEI use or the time of initiation of ACEI did not significantly affect age-related increase in LGE. ACEI attenuated the age-related decline in LVEF only in patients with DMD or BMD and reduced LVEF, suggesting that further investigation on prophylactic use of cardioprotective therapy in these patients is warranted.

The relationship between prenatal psychological stress and placental abruption in Japan, The Japan Environment and Children's Study (JECS).
Kawanishi Y, Yoshioka E, Saijo Y, Itoh T, Miyamoto T, Sengoku K, Ito Y, Ito S, Miyashita C, Araki A, Endo T, Cho K, Minakami H, Kishi R, Japan Environment, Children’s Study Group
PloS one, 14, 7, e0219379, 2019年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Prenatal psychological stress may increase the risk of placental abruption (PA). This study aimed to clarify the effects of psychological distress during pregnancy and exposure to stressful life events in the year before or during pregnancy on the occurrence of PA in Japanese women. METHODS: Using a nationwide prospective birth cohort study, we obtained data from 103,099 women between January 2011 and March 2014. Information on exposure to 14 stressful life events and psychological distress (Kessler 6 scale) was collected using a self-administered questionnaire during pregnancy. Clinical diagnoses of PA were obtained from medical records. A total of 80,799 women with singleton births were analyzed using logistic regression models that adjusted for possible confounders. RESULTS: PA was diagnosed in 335 (0.4%) women. There was no significant difference in the Kessler 6 score during pregnancy between the PA group and non-PA group. Exposure to the death of a child in the year before or during pregnancy was significantly associated with PA in multigravid women (adjusted odds ratio [aOR] 3.57; 95% confidence interval [CI] 1.50-8.34). A spouse's loss of employment was significantly associated with PA in parous women (aOR 3.25; 95% CI 1.40-7.56). CONCLUSIONS: This study identified the possible effects of exposure to the death of a child on PA occurrence that adjusted for important confounding factors.

Identifying a risk score for childhood obesity based on predictors identified in pregnant women and 1-year-old infants: An analysis of the data of the Hokkaido Study on Environment and Children's Health.
Saijo Y, Ito Y, Yoshioka E, Sato Y, Minatoya M, Araki A, Miyashita C, Kishi R
Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology, 28, 3, 81, 89, 2019年, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, This study aimed to construct a childhood obesity risk index based on predictors identified in pregnant women and 1-yr-old infants. The primary outcome was an identified obesity index of > 20% at 6-8 yr of age. Of a total sample size of 6,846 mother-child pairs, 80% and 20% were randomly allocated to the derivation and validation cohorts, respectively. For the derivation cohort, univariate and multivariate logistic regression analyses of data were conducted to identify the final predictors to determine the childhood obesity risk score algorithm. These included pre-pregnancy body mass index (BMI), child's gender, smoking during pregnancy, education, and obesity index at one yr of age. The β coefficients for categories of predictor variables were each divided by the smallest value among them. The quotient was rounded off to the integer and assigned to the risk score, and a value of zero was assigned to reference categories. A total risk score was calculated for each individual. A cutoff point ≥ 16 had 22.2% and 21.8% positive predictive values in the derivation and validation cohorts, respectively. In conclusion, the childhood obesity risk score algorithm was constructed based on generic predictors that can be easily obtained from maternal and child health handbooks.

Effectiveness and Safety of Double-Blind, Placebo-Controlled, Low-Dose Oral Immunotherapy with Low Allergen Egg-Containing Cookies for Severe Hen's Egg Allergy: A Single-Center Analysis.
Yuri Takaoka, Akihiro Maeta, Kyoko Takahashi, Yoichi M Ito, Shinichi Takahashi, Takahiro Muroya, Amane Shigekawa, Yuki Tsurinaga, Norihito Iba, Yukinori Yoshida, Makoto Kameda, Satoru Doi
International archives of allergy and immunology, 180, 4, 244, 249, KARGER, 2019年, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: The usefulness of low-dose oral immunotherapy (OIT) for the treatment of egg allergy has been unclear. OBJECTIVE: To evaluate the efficacy and safety of OIT with low allergen cookies (LACs) containing a low dose of hen's egg. METHOD: Thirty-three patients with severe hen's egg allergy were randomly administered either OIT with LACs (n = 21) or placebo (n = 12). Two patients in the LACs group withdrew before completing OIT. The primary endpoint was the number of good responders (G-R), patients with negative results in the oral food challenge (OFC) with a final dose of 2 g hard-boiled egg whites after 4 months of OIT, in each group. Total OFC Aichi score for anaphylaxis/cumulative protein dose (TS/Pro) as the marker of severity of food allergy was also compared. Adverse events during OIT were evaluated using patients' diaries. RESULTS: The proportion of G-R in the LACs group was higher than in the placebo group (7/19 [37%] vs. 1/12 [8%], χ2 test; p = 0.077). The TS/Pro after OIT in the LACs group was lower than in the placebo group (median score, 44.2 vs. 104.1, p = 0.059; Mann-Whitney U test). The threshold and TS/Pro before and after OIT significantly improved in the LACs group (p = 0.015, p = 0.027, respectively; Wilcoxon signed-rank test). There were 99 recorded incidences of symptoms of 1,938 intake events in the LACs group during OIT. Of these, 90 were mild; no severe symptoms occurred. CONCLUSIONS: OIT with LACs potentially increases the OFC threshold and decreases allergy severity and is a relatively safe treatment modality.

Complications Related to the Initial Trocar Insertion of 3 Different Techniques: A Systematic Review and Meta-analysis
Nishimura, Mai Department of Obstetrics, Gynecology, Teine Keijinkai Hospital, Matsumoto, Sachiko Department of Obstetrics, Gynecology, Teine Keijinkai Hospital, Ohara, Yasuhiro Department of Obstetrics, Gynecology, Teine Keijinkai Hospital, Minowa, Kaoru Department of Obstetrics, Gynecology, Teine Keijinkai Hospital, Tsunematsu, Risa Department of Obstetrics, Gynecology, Teine Keijinkai Hospital, Takimoto, Kanako Department of Obstetrics, Gynecology, Teine Keijinkai Hospital, Imai, Kazuaki Department of Obstetrics, Gynecology, Teine Keijinkai Hospital, Tsuzuki, Yoko Department of Obstetrics, Gynecology, Teine Keijinkai, Hospital, Ota, Hajime Department of Obstetrics, Gynecology, Teine Keijinkai Hospital, Nakajima, Ayako Department of Obstetrics, Gynecology, Teine Keijinkai, Hospital, Fukushi, Yoshiyuki Department of Obstetrics, Gynecology, Teine Keijinkai Hospital, Wada, Shinichiro Department of Obstetrics, Gynecology, Teine Keijinkai Hospital, Fujino, Takafumi Department of Obstetrics, Gynecology, Teine Keijinkai Hospital, M.Ito, Yoichi Department, of Biostatistics, Faculty of Medicine, Graduate School of, Medicine, Hokkaido University
The Journal of Minimally Invasive Gynecology, 26, 1, 63, 70, ELSEVIER SCIENCE INC, 2019年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, This systematic review aimed to investigate complications related to initial trocar insertion among 3 different laparoscopic techniques: Veress needle (VN) entry, direct trocar entry (DTE), and open entry (OE). A literature search was completed, and complications were assessed. Major vessel injury, gastrointestinal injury, and solid organ injury were defined as major complications. Minor complications were defined as subcutaneous emphysema, extraperitoneal insufflation, omental emphysema, trocar site bleeding, and trocar site infection. Arm-based network meta-analyses were performed to identify the differences in complications among the 3 techniques. Seventeen studies were included in the quantitative analysis. DTE resulted in fewer major complications when compared with VN entry although the difference was not significant (p = .23) as well as significantly fewer minor complications (p < .001). There were no significant differences in minor complications when comparing OE and DTE (p = .74). Fewer major complications were observed with OE compared with VN entry although the difference was not significant (p = .31). There were significantly fewer minor complications for patients who underwent OE (p = .01). DTE patients experienced the least number of minor complications followed by VN entry and OE. In conclusion, major complications are extremely rare, and all 3 insertion methods can be performed without mortality.

Effects of coronary revascularization on global coronary flow reserve in stable coronary artery disease.
Tadao Aikawa, Masanao Naya, Masahiko Obara, Osamu Manabe, Keiichi Magota, Kazuhiro Koyanagawa, Naoya Asakawa, Yoichi M Ito, Tohru Shiga, Chietsugu Katoh, Toshihisa Anzai, Hiroyuki Tsutsui, Venkatesh L Murthy, Nagara Tamaki
Cardiovascular research, 115, 1, 119, 129, OXFORD UNIV PRESS, 2019年01月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Aims: Coronary flow reserve (CFR) is an integrated measure of the entire coronary vasculature, and is a powerful prognostic marker in coronary artery disease (CAD). The extent to which coronary revascularization can improve CFR is unclear. This study aimed to evaluate the impact of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) on CFR in patients with stable CAD. Methods and results: In a prospective, multicentre observational study, CFR was measured by 15O-water positron emission tomography as the ratio of stress to rest myocardial blood flow at baseline and 6 months after optimal medical therapy (OMT) alone, PCI, or CABG. Changes in the SYNTAX and Leaman scores were angiographically evaluated as indicators of completeness of revascularization. Follow-up was completed by 75 (25 OMT alone, 28 PCI, and 22 CABG) out of 82 patients. The median SYNTAX and Leaman scores, and baseline CFR were 14.5 [interquartile range (IQR): 8-24.5], 5.5 (IQR: 2.5-12.5), and 1.94 (IQR: 1.67-2.66), respectively. Baseline CFR was negatively correlated with the SYNTAX (ρ = -0.40, P < 0.001) and Leaman scores (ρ = -0.33, P = 0.004). Overall, only CABG was associated with a significant increase in CFR [1.67 (IQR: 1.14-1.96) vs. 1.98 (IQR: 1.60-2.39), P < 0.001]. Among patients with CFR <2.0 (n = 41), CFR significantly increased in the PCI [1.70 (IQR: 1.42-1.79) vs. 2.21 (IQR: 1.78-2.49), P = 0.002, P < 0.001 for interaction between time and CFR] and CABG groups [1.28 (IQR: 1.13-1.80) vs. 1.86 (IQR: 1.57-2.22), P < 0.001]. The reduction in SYNTAX or Leaman scores after PCI or CABG was independently associated with the percent increase in CFR after adjusting for baseline characteristics (P = 0.012 and P = 0.011, respectively). Conclusion: Coronary revascularization ameliorated reduced CFR in patients with obstructive CAD. The degree of improvement in angiographic CAD burden by revascularization was correlated with magnitude of improvement in CFR.

Nationwide survey on the organ-specific prevalence and its interaction with sarcoidosis in Japan
Takeshi Hattori, Satoshi Konno, Noriharu Shijubo, Tetsuo Yamaguchi, Yukihiko Sugiyama, Sakae Honma, Naohiko Inase, Yoichi M. Ito, Masaharu Nishimura
Scientific Reports, 8, 1, 9440, 9440, Nature Publishing Group, 2018年12月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Previous studies attempted to characterize the subjects with sarcoidosis according to differences in sex, age, and the presence of specific organ involvement. However, significant interactions among these factors precluded a clear conclusion based on simple comparison. This study aimed to clarify the age- and sex-stratified prevalence of specific organ involvement and the heterogenous nature of sarcoidosis. Using the data of 9,965 patients who were newly registered into a database at the Ministry of Health, Labour and Welfare, Japan between 2002 and 2011, we evaluated the age- and sex-specific prevalence of the eye, lung, and skin involvement of sarcoidosis. We also attempted corresponding analysis considering multiple factors. As compared with several decades ago, the monophasic age distribution in men became biphasic, and the biphasic distribution in women, monophasic. The prevalence of pulmonary and cutaneous lesions was significantly associated with age, whereas the prevalence of ocular involvement showed a biphasic pattern. The prevalence of bilateral hilar lymphadenopathy was significantly higher, whereas the prevalence of diffuse lung shadow was significantly lower, in subjects with ocular involvement than those without ocular involvement. Corresponding analysis visually clarified the complex interactions among factors. Our results contribute to a better understanding of the heterogeneous features of sarcoidosis.

Automated noninvasive detection of idiopathic scoliosis in children and adolescents: A principle validation study
Sudo, Hideki Department of, Advanced Medicine for Spine, Spinal Cord Disorders, Faculty of Medicine, Graduate of Medicine, Hokkaido University, Kokabu, Terufumi Department of Orthopaedic Surgery, Hokkaido University Hospital, Abe, Yuichiro Department of Orthopaedic Surgery, Eniwa Hospital, Iwata, Akira Department, of Orthopaedic Surgery, Hokkaido University Hospital, Yamada, Katsuhisa Department of Orthopaedic Surgery, Hokkaido University Hospital, M. Ito, Yoichi Department, of Biostatistics, Hokkaido University, Graduate School of, Medicine, Iwasaki, Norimasa Department of Orthopaedic Surgery, Hokkaido University, Hospital, Kanai, Satoshi Division of, Systems Science, Informatics, Hokkaido University, Graduate School of, Information Science, Technology
Scientific Reports, 8, 1, 17714, 17714, NATURE PUBLISHING GROUP, 2018年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Idiopathic scoliosis is the most common pediatric musculoskeletal disorder that causes a three-dimensional deformity of the spine. Early detection of this progressive aliment is essential. The aim of this study is to determine outcomes using a newly developed automated asymmetry-evaluation system for the surface of the human back using a three-dimensional depth sensor. Seventy-six human subjects suspected to have idiopathic scoliosis were included in this study. Outcome measures include patient demographics, radiographic measurements, and asymmetry indexes defined in the automated asymmetry-recognition system. The mean time from scanning to analysis was 1.5 seconds. For predicting idiopathic scoliosis of greater than 25°, the area under the curve was 0.96, sensitivity was 0.97, and specificity was 0.88. The coefficient of variation for repeatability analyses using phantom models was 1-4%. The intraclass correlation coefficient obtained for intra-observer repeatability for human subjects was 0.995. The system three-dimensionally scans multiple points on the back, enabling an automated evaluation of the back's asymmetry in a few seconds. This study demonstrated discriminative ability in determining whether an examinee requires an additional x-ray to confirm diagnosis.

Uncertainties of Normal Tissue Complication Probability (NTCP) and NTCP Difference between Radiation Treatment Modalities for Radiation-Induced Liver Toxicity in Child-Pugh A Primary Liver Cancer Patients
A. Prayongrat, K. Kobashi, Y. Ito, N. Katoh, Y. Dekura, N. Amornwichet, S. Shimizu, H. Shirato
International Journal of Radiation Oncology*Biology*Physics, 102, 3, e65, e66, Elsevier BV, 2018年11月
研究論文（学術雑誌）

Analysis of Beam Delivery Times and Dose Rates for the Treatment of Mobile Tumors Using Real Time Image Gated Spot-Scanning Proton Beam Therapy
S. Shimizu, T. Yoshimura, N. Katoh, T. Inoue, T. Hashimoto, K. Nishioka, S. Takao, T. Matsuura, N. Miyamoto, Y.M. Ito, K. Umegaki, H. Shirato
International Journal of Radiation Oncology*Biology*Physics, 102, 3, S182, S183, Elsevier BV, 2018年11月
研究論文（学術雑誌）

Impact of Abdominal Visceral Adiposity on Adult Asthma Symptoms.
Goudarzi H, Konno S, Kimura H, Makita H, Matsumoto M, Takei N, Kimura H, Shimizu K, Suzuki M, Ito YM, Nishimura M, Hi-CARAT investigators
The journal of allergy and clinical immunology. In practice, 7, 4, 1222, 1229, ELSEVIER SCIENCE BV, 2018年11月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Previous studies have shown the association of anthropometric measures with poor asthma symptoms, especially among women. However, the potential influence of visceral adiposity on asthma symptoms has not been investigated well. OBJECTIVE: In this study, we have evaluated whether visceral adiposity is related to poor adult asthma symptoms independent of anthropometric measures and sex. If this relationship presented, we investigated whether it is explained by influence on pulmonary functions and/or obesity-related comorbidities. METHODS: We analyzed data from 206 subjects with asthma from Japan. In addition to anthropometric measures (body mass index and waist circumference), abdominal visceral and subcutaneous fat were assessed by computed tomography scan. Quality of life was assessed using the Japanese version of the Asthma Quality of Life Questionnaire. RESULTS: All obesity indices had inverse association with reduced asthma quality of life among females. However, only the visceral fat area showed a statistical inverse association with Asthma Quality of Life Questionnaire in males. Only abdominal visceral fat was associated with higher gastroesophageal reflux disease and depression scores. Although all obesity indices showed inverse association with functional residual capacity, only visceral fat area had a significant inverse association with FEV1 % predicted, independent of other obesity indices. CONCLUSIONS: Regardless of sex, abdominal visceral fat was associated with reduced asthma quality of life independent of other obesity indices, and this may be explained by the impact of abdominal visceral fat on reduced FEV1 % predicted and higher risk for gastroesophageal reflux disease and depression. Therefore, visceral adiposity may have more clinical influence than any other obesity indices on asthma symptoms.

An acellular bioresorbable ultra-purified alginate gel promotes intervertebral disc repair: A preclinical proof-of-concept study.
Takeru Tsujimoto, Hideki Sudo, Masahiro Todoh, Katsuhisa Yamada, Koji Iwasaki, Takashi Ohnishi, Naoki Hirohama, Takayuki Nonoyama, Daisuke Ukeba, Katsuro Ura, Yoichi M Ito, Norimasa Iwasaki
EBioMedicine, 37, 521, 534, ELSEVIER SCIENCE BV, 2018年11月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The current surgical procedure of choice for lumbar intervertebral disc (IVD) herniation is discectomy. However, defects within IVD produced upon discectomy may impair tissue healing and predispose patients to subsequent IVD degeneration. This study aimed to investigate whether the use of an acellular bioresorbable ultra-purified alginate (UPAL) gel implantation system is safe and effective as a reparative therapeutic strategy after lumbar discectomy. METHODS: Human IVD cells were cultured in a three-dimensional system in UPAL gel. In addition, lumbar spines of sheep were used for mechanical analysis. Finally, the gel was implanted into IVD after discectomy in rabbits and sheep in vivo. FINDINGS: The UPAL gel was biocompatible with human IVD cells and promoted extracellular matrix production after discectomy, demonstrating sufficient biomechanical characteristics without material protrusion. INTERPRETATION: The present results indicate the safety and efficacy of UPAL gels in a large animal model and suggest that these gels represent a novel therapeutic strategy after discectomy in cases of lumbar IVD herniation. FUND: Grant-in-Aid for the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Japan Agency for Medical Research and Development, and the Mochida Pharmaceutical Co., Ltd.

Contrasting associations of maternal smoking and pre-pregnancy BMI with wheeze and eczema in children
Houman Goudarzi, Satoshi Konno, Hirokazu Kimura, Atsuko Araki, Chihiro Miyashita, Sachiko Itoh, Yu Ait Bamai, Hiroki Kimura, Kaoruko Shimizu, Masaru Suzuki, Yoichi M. Ito, Masaharu Nishimura, Reiko Kishi
Science of the Total Environment, 639, 1601, 1609, Elsevier B.V., 2018年10月15日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Childhood allergies are dynamic and associated with environmental factors. The influence of prenatal maternal smoking and obesity on childhood allergies and their comorbidities remains unclear, especially in prospective cohorts with serial longitudinal observations. Objective: We examined time trends in the prevalence and comorbidity of childhood allergies, including wheeze, eczema, and rhinoconjunctivitis, using a large-scale, population-based birth cohort in Japan, and assessed the effects of prenatal maternal smoking and BMI on the risk of childhood allergies. Methods: Parents completed the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires about symptoms of allergies and their risk factors at age 1, 2, 4, and 7 years. Complete data from all pre- and postnatal questionnaires at age 1, 2, 4, and 7 were available for 3296 mother–child pairs. Results: We observed significant overlap of childhood allergies at 1, 2, 4, and 7 years. Maternal serum cotinine during pregnancy was associated with increased risk of wheezing in the children at age 1, 2, and 4 but disappeared at age 7. In contrast, maternal cotinine levels were inversely associated with the prevalence of eczema in children at age 7. We additionally observed that maternal pre-pregnancy BMI, not children's BMI, had a positive association with wheeze and an inverse association with eczema in 7-year-old children, respectively. We did not find any association of examined maternal factors and rhinoconjunctivitis. Conclusions: We demonstrated contrasting association of prenatal maternal smoking and high BMI with postnatal wheeze and eczema. For precise assessment of allergy-associated risk factors, we need to contrast risk factors for different allergic diseases since focusing solely on one allergic disease may result in misleading information on the role of different risk factors.

Predictive factors for hyperglycaemic progression in patients with schizophrenia or bipolar disorder
Kusumi, Ichiro Department of Psychiatry, Hokkaido University, Graduate School of, Medicine, Arai, Yuki Department of Psychiatry, Wakkanai City Hospital, Okubo, Ryo Department of Psychiatry, Hokkaido University, Graduate School of Medicine, Honda Memorial, Hospital, Honda, Minoru Honda Memorial Hospital, Matsuda, Yasuhiro Department of Psychiatry, Nara Medical University, Matsuda, Yukihiko Hosogi, Unity, Hospital, Tochigi, Akihiko Tomakomai, Midorigaoka Hospital, Takekita, Yoshiteru Department of Neuropsychiatry, Kansai Medical University, Yamanaka, Hiroyoshi Okamoto Hospital, Uemura, Keiichi Department of Psychiatry, Sapporo City General Hospital, Ito, Koichi, Sapporo, Hanazono Hospital, Tsuchiya, Kiyoshi Tomakomai, Midorigaoka Hospital, Yamada, Jun, Kei-ai Hospital, Yoshimura, Bunta Okayama, Psychiatric Medical Center, Mitsui, Nobuyuki Department of Psychiatry, Hokkaido University, Graduate School of Medicine, Department of Psychiatry, Wakkanai City Hospital, Matsubara, Sigehiro Department of Neuropsychiatry, Obihiro National, Hospital, Segawa, Takayuki Okamoto, Hospital, Nishi, Nobuyuki Nishi, Hospital, Sugawara, Yasufumi Teine, Hospital, Kako, Yuki Department of Psychiatry, Hokkaido University, Graduate School of Medicine, Shinkawa, Ikuta Okayama, Psychiatric Medical Center, Shinohara, Kaoru, Sapporo, Suzuki Hospital, Konishi, Akiko Okayama, Psychiatric Medical Center, Iga, Junichi Department of Psychiatry, Tokushima University, Department of Psychiatry, Ehime University, Hashimoto, Naoki Department of Psychiatry, Hokkaido University, Graduate School of, Medicine, Inomata, Shinsaku Hizen, Psychiatric Center, Tsukamoto, Noriko Hakodate, Watanabe Hospital, Ito, Hiroto National, Institute of, Occupational Safety, d Health, National Center of, Neurology, Psychiatry, M. Ito, Yoichi Department, of Biostatistics, Hokkaido University, Graduate School of, Medicine, Sato, Norihiro Hokkaido, University Hospital Clinical Research, Medical Innovation Center
BJPsych Open, 4, 6, 454, 460, CAMBRIDGE UNIV PRESS, 2018年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Patients with schizophrenia or bipolar disorder have a high risk of developing type 2 diabetes. Aims: To identify predictive factors for hyperglycaemic progression in individuals with schizophrenia or bipolar disorder and to determine whether hyperglycaemic progression rates differ among antipsychotics in regular clinical practice. Method: We recruited 1166 patients who initially had normal or prediabetic glucose levels for a nationwide, multisite, l-year prospective cohort study to determine predictive factors for hyperglycaemic progression. We also examined whether hyperglycaemic progression varied among patients receiving monotherapy with the six most frequently used antipsychotics. Results: High baseline serum triglycerides and coexisting hypertension significantly predicted hyperglycaemic progression. The six most frequently used antipsychotics did not significantly differ in their associated hyperglycaemic progression rates over the 1-year observation period. Conclusions: Clinicians should carefully evaluate baseline serum triglycerides and coexisting hypertension and perform strict longitudinal monitoring irrespective of the antipsychotic used. Declaration of interest: The authors report no financial or other relationship that is relevant to the subject of this article. Relevant financial activities outside the submitted work are as follows. I.K. has received honoraria from Astellas, Chugai Pharmaceutical, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, Janssen Pharmaceutical, Kyowa Hakko Kirin, Meiji Seika Pharma, MSD, Nippon Chemiphar, Novartis Pharma, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Tanabe Mitsubishi Pharma, Shionogi and Yoshitomiyakuhin; has received research/grant support from AbbVie GK, Asahi Kasei Pharma, Astellas, Boehringer Ingelheim, Chugai Pharmaceutical, Daiichi Sankyo, Dainippon Sumitomo Pharma, Eisai, Eli Lilly, GlaxoSmithKline, Kyowa Hakko Kirin, Meiji Seika Pharma, MSD, Novartis Pharma, Ono Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Takeda Pharmaceutical, Tanabe Mitsubishi Pharma, Shionogi and Yoshitomiyakuhin; and is a member of the advisory boards of Dainippon Sumitomo Pharma and Tanabe Mitsubishi Pharma. Y.T. has received speaker's honoraria from Dainippon-Sumitomo Pharma, Otsuka, Meiji-Seika Pharma, Janssen Pharmaceutical, Daiichi-Sankyo Company, UCB Japan and Ono Pharmaceutical. K.U. has received honoraria from Dainippon Sumitomo Pharma, Eisai, Eli Lilly, Janssen Pharmaceutical, Kyowa Hakko Kirin, Meiji Seika Pharma, MSD, Takeda Pharmaceutical, Hisamitsu Pharmaceutical, Otsuka Pharmaceutical, Pfizer, Tanabe Mitsubishi Pharma, Shionogi and Yoshitomiyakuhin. B.Y. has received speaker's honoraria from Otsuka Pharmaceutical and Janssen Pharmaceutical. J. I. has received honoraria from Dainippon Sumitomo Pharma, Eli Lilly, Janssen Pharmaceutical, Meiji Seika Pharma, MSD, Novartis Pharma, Otsuka Pharmaceutical and Mochida Pharma.

Stereotactic body radiotherapy to treat small lung lesions clinically diagnosed as primary lung cancer by radiological examination: A prospective observational study
Tetsuya Inoue, Norio Katoh, Yoichi M Ito, Tomoki Kimura, Yasushi Nagata, Kengo Kuriyama, Hiroshi Onishi, Tadamasa Yoshitake, Yoshiyuki Shioyama, Yusuke Iizuka, Koji Inaba, Koji Konishi, Masaki Kokubo, Katsuyuki Karasawa, Takuyo Kozuka, Kensuke Tanaka, Jun Sakakibara-Konishi, Ichiro Kinoshita, Hiroki Shirato
Lung Cancer, 122, 107, 112, Elsevier Ireland Ltd, 2018年08月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Objectives: Even with advanced image guidance, biopsies occasionally fail to diagnose small lung lesions, which are highly suggestive of primary lung cancer by radiological examination. The aim of this study was to evaluate the outcome of stereotactic body radiotherapy (SBRT) to treat small lung lesions clinically diagnosed as primary lung cancer. Materials and methods: This is a prospective, multi-institutional observation study. Strict inclusion and exclusion criteria were determined in a nation-wide consensus meeting and used to include patients who were clinically diagnosed with primary lung cancer using precise imaging modalities, for whom further surgical intervention was not feasible, who refused watchful waiting, and who were highly tolerable of SBRT with informed consent. SBRT was performed with 48 Gy in 4 fractions at the tumor isocenter. Results: From August 2009 to August 2014, 62 patients from 11 institutions were enrolled. Their median age was 80 years. The tumors ranged in size from 9 to 30 mm in diameter (median, 18 mm). The median follow-up interval was 55 months. The 3-year overall survival rate was 83.3% (95% confidence interval (CI) 71.1–90.7%) for all the patients and 94.7% (95% CI 68.1–99.2%) for the patients younger than 75 years. Local failure, regional lymph node metastases and distant metastases occurred in 4 (6.4%), 3 (4.8%) and 11 (17.7%) patients, respectively. Grades 3 and 4 toxicities were observed in 8 (12.9%) patients and 1 (1.6%) patient, respectively. No grade 5 toxicities were observed. Conclusions: SBRT is safe and effective for patients with small lung lesions clinically diagnosed as primary lung cancer that satisfied the proposed strict indication criteria as previously reported. A prospective interventional study is required to ascertain if SBRT is an alternative strategy for these patients.

Should sulfonylurea be discontinued or maintained at the lowest dose when starting ipragliflozin? A multicenter observational study in Japanese patients with type 2 diabetes.
Takahashi K, Cho KY, Nakamura A, Miya A, Miyoshi A, Yamamoto C, Nomoto H, Niwa H, Takahashi K, Manda N, Kurihara Y, Aoki S, Ito YM, Atsumi T, Miyoshi H
Journal of diabetes investigation, 10, 2, 429, 438, WILEY, 2018年08月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, AIMS/INTRODUCTION: We investigated the difference in efficacy and safety between discontinuation and maintaining of sulfonylurea when adding a sodium-glucose cotransporter 2 inhibitor. MATERIALS AND METHODS: In the present multicenter, prospective observational study, 200 patients with type 2 diabetes treated with sulfonylurea and with a need to add ipragliflozin were enrolled and divided into two groups: discontinued sulfonylurea (Discontinuation group) or maintained sulfonylurea, but at the lowest dose (Low-dose group) when adding ipragliflozin. We compared the two groups after 24 weeks using propensity score matching to adjust for differences between the groups. RESULTS: In the matched cohort (58 patients in each group), baseline characteristics of both groups were balanced. The primary outcome of the proportion of patients with non-exacerbation in glycated hemoglobin after 24 weeks was 91.4% in the Low-dose group and 75.9% in the Discontinuation group, a significant difference (P = 0.024). However, bodyweight was significantly decreased in the Discontinuation group compared with the Low-dose group (-4.4 ± 2.1 kg vs -2.9 ± 1.9 kg, P < 0.01). Similarly, liver enzyme improvement was more predominant in the Discontinuation group. A logistic regression analysis showed that high-density lipoprotein cholesterol, age and sulfonylurea dose were independent factors associated with non-exacerbation of glycated hemoglobin in the Discontinuation group. CONCLUSIONS: The purpose of using ipragliflozin should be considered when making the decision to discontinue or maintain sulfonylurea at the lowest dose. Furthermore, low high-density lipoprotein cholesterol level, low dose of sulfonylurea and younger age were possible markers to not show worsening of glycemic control by discontinuing sulfonylurea.

Validation of the nomogram for predicting 90-day mortality after radical cystectomy in a Japanese cohort
Osawa, Takahiro Department of Urology, Hokkaido University, Graduate School of, Medicine, Abe, Takashige Department of Urology, Hokkaido University, Graduate School of, Medicine, Takada, Norikata Department of Urology, Hokkaido University, Graduate School of Medicine, M. Ito, Yoichi Department, of Biostatistics, Hokkaido University, Graduate School of, Medicine, Murai, Sachiyo Department of Urology, Hokkaido University, Graduate School of, Medicine, Shinohara, Nobuo Department of Urology, Hokkaido University, Graduate School of Medicine
International Journal of Urology, 25, 7, 699, 701, WILEY, 2018年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）

Prediction of major depressive episodes and suicide-related ideation over a 3-year interval among Japanese undergraduates.
Mitsui, Nobuyuki Department of Psychiatry, Hokkaido University, Graduate School of, Medicine, Asakura, SAtoshi Department of Psychiatry, Hokkaido University, Graduate School of Medicine, Takanobu, Keisuke Department of Psychiatry, Hokkaido University, Graduate School of Medicine, Watanabe, Shinya Department of Psychiatry, Hokkaido University, Graduate School of, Medicine, Toyoshima, Kuniyoshi Department of Psychiatry, Hokkaido University, Graduate School of, Medicine, Kako, Yuki Department of Psychiatry, Hokkaido University, Graduate School of, Medicine, Ito, Yoichi M. Department, of Biostatistics, Hokkaido University, Graduate School of, Medicine, Kusumi, Ichiro Department of Psychiatry, Hokkaido University, Graduate School of Medicine
PloS one., 13, 7, e0201047, PUBLIC LIBRARY SCIENCE, 2018年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Suicide has been a leading cause of death among young adult populations in Japan. The aim of this study was to predict major depressive episodes (MDEs) and suicide-related ideation among university students using the Patient Health Questionnaire-9 (PHQ-9) and the Temperament and Character Inventory (TCI). METHODS: The subjects were 2194 university students who completed the PHQ-9 and TCI in the 1st year (T1) and the PHQ-9 in the 4th year (T2) of university. Multiple logistic regression analysis was performed to predict MDEs and suicide-related ideation at T2. Moreover, recursive partitioning analyses were conducted to reveal the future risk of MDEs and suicide-related ideation. RESULTS: The multiple logistic regression analyses of MDEs and suicide-related ideation at T2 revealed that depressive episodes, suicide-related ideation, and low self-directedness(SD) scores at T1 were significant predictors. The area under the curve of the model for MDEs was 0.858 and that for suicide-related ideation was 0.741. The recursive partitioning analyses revealed that a PHQ-9 summary score ≥15 at T1 predicted a high risk of MDEs at T2 and that both a PHQ-9 summary score ≥5 and a PHQ-9 #9 score ≥1 predicted a high risk of suicide-related ideation at T2. CONCLUSIONS: MDEs, suicide-related ideation, and low SD scores are significant predictors of future MDEs and suicide-related ideation.

Is There an Association Between Borderline-to-mild Dysplasia and Hip Osteoarthritis? Analysis of CT Osteoabsorptiometry.
Tohru Irie, Daisuke Takahashi, Tsuyoshi Asano, Ryuta Arai, Muhammad Alaa Terkawi, Yoichi M Ito, Norimasa Iwasaki
Clinical orthopaedics and related research, 476, 7, 1455, 1465, LIPPINCOTT WILLIAMS & WILKINS, 2018年07月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The definitive treatment of borderline-to-mild dysplasia remains controversial. A more comprehensive understanding of the etiology of osteoarthritis (OA) and clarification of any possible association between borderline-to-mild dysplasia and the pathogenesis of OA are essential. QUESTIONS/PURPOSES: (1) Does the distribution of acetabular subchondral bone density increase according to dysplasia severity? (2) Is there an association between borderline-to-mild dysplasia and OA pathogenesis? METHODS: We evaluated bilateral hips of patients with developmental dysplasia of the hip who underwent eccentric rotational acetabular osteotomy (ERAO) for inclusion in the dysplasia group and contralateral hips of patients with unilateral idiopathic osteonecrosis of the femoral head (ONFH) who underwent curved intertrochanteric varus osteotomy (CVO) for the control group. ERAO was performed in 46 patients and CVO was performed in 32 patients between January 2013 and August 2016 at our institution. All patients underwent bilateral hip CT. The study included 55 hips categorized according to dysplasia severity: (1) borderline-mild, 19 hips (15° ≤ lateral center-edge angle [LCEA] < 25°); (2) moderate, 20 hips (5° ≤ LCEA < 15°); (3) severe, 16 hips (LCEA < 5°); and (4) control, 15 hips. Thirty-seven dysplastic hips (age < 15 or > 50 years old, prior hip surgery, subluxation, aspherical femoral head, cam deformity, and radiographic OA) and 17 control hips (age < 15 or > 50 years old, bilateral ONFH, LCEA < 25° or ≥ 35°, cam deformity, and radiographic OA) were excluded. CT-osteoabsorptiometry (OAM) predicts physiologic biomechanical conditions in joints by evaluating subchondral bone density. We evaluated the distribution of subchondral bone densities in the acetabulum with CT-OAM, dividing the stress distribution map into six segments: anteromedial, anterolateral, centromedial, centrolateral, posteromedial, and posterolateral. We calculated the percentage of high-density area, which was defined as the upper 30% of Hounsfield units values in each region and compared least square means difference estimated by the random intercept model among the four groups. RESULTS: In all regions, the percentage of high-density area did not differ between the borderline-mild group and the control (eg, anterolateral, 16.2 ± 5.6 [95% CI, 13.4 to 18.9] versus 15.5 ± 5.7 [95% CI, 12.4 to 18.5, p = 0.984]; centrolateral, 39.1 ± 5.7 [95% CI, 36.4 to 41.8] versus 39.5 ± 4.7 [95% CI, 36.6 to 42.5, p = 0.995]; posterolateral, 10.9 ± 5.2 [95% CI, 8.0 to 13.8] versus 15.1 ± 6.8 [95% CI, 11.7 to 18.5, p = 0.389]). In the anterolateral region, a smaller percentage of high-density area was observed in the borderline-mild group than in both the moderate group (16.2 ± 5.6 [95% CI, 13.4-18.9] versus 28.2 ± 5.1 [95% CI, 25.5-30.9], p < 0.001) and the severe group (16.2 ± 5.6 [95% CI, 13.4-18.9] versus 22.2 ± 6.8 [95% CI, 19.2-25.2, p = 0.026). CONCLUSIONS: Our results suggest that the cumulative hip stress distribution in borderline-to-mild dysplasia was not concentrated on the lateral side of the acetabulum, unlike severe dysplasia. CLINICAL RELEVANCE: Based on the stress distribution pattern, our results may suggest that there is no association between borderline-to-mild dysplasia and the pathogenesis of OA. Further studies are needed to evaluate the association between borderline-to-mild dysplasia and instability of the hip.

Antitumor effects of radionuclide treatment using α-emitting meta-211At-astato-benzylguanidine in a PC12 pheochromocytoma model
Yasuhiro Ohshima, Hitomi Sudo, Shigeki Watanabe, Kotaro Nagatsu, Atsushi B. Tsuji, Tetsuya Sakashita, Yoichi M. Ito, Keiichiro Yoshinaga, Tatsuya Higashi, Noriko S. Ishioka
European Journal of Nuclear Medicine and Molecular Imaging, 45, 6, 999, 1010, Springer Berlin Heidelberg, 2018年06月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Purpose: Therapeutic options for patients with malignant pheochromocytoma are currently limited, and therefore new treatment approaches are being sought. Targeted radionuclide therapy provides tumor-specific systemic treatments. The β-emitting radiopharmaceutical meta-131I-iodo-benzylguanidine (131I-MIBG) provides limited survival benefits and has adverse effects. A new generation of radionuclides for therapy using α-particles including meta-211At-astato-benzylguanidine (211At-MABG) are expected to have strong therapeutic effects with minimal side effects. However, this possibility has not been evaluated in an animal model of pheochromocytoma. We aimed to evaluate the therapeutic effects of the α-emitter 211At-MABG in a pheochromocytoma model. Methods: We evaluated tumor volume-reducing effects of 211At-MABG using rat pheochromocytoma cell line PC12 tumor-bearing mice. PC12 tumor-bearing mice received intravenous injections of 211At-MABG (0.28, 0.56, 1.11, 1.85, 3.70 and 5.55 MBq
five mice per group). Tumor volumes were evaluated for 8 weeks after 211At-MABG administration. The control group of ten mice received phosphate-buffered saline. Results: The 211At-MABG-treated mice showed significantly lower relative tumor growth during the first 38 days than the control mice. The relative tumor volumes on day 21 were 509.2% ± 169.1% in the control mice and 9.6% ± 5.5% in the mice receiving 0.56 MBq (p <
0.01). In addition, the mice treated with 0.28, 0.56 and 1.11 MBq of 211At-MABG showed only a temporary weight reduction, with recovery in weight by day 10. Conclusion: 211At-MABG exhibited a strong tumor volume-reducing effect in a mouse model of pheochromocytoma without weight reduction. Therefore, 211At-MABG might be an effective therapeutic agent for the treatment of malignant pheochromocytoma.

An epigenome-wide study of cord blood DNA methylations in relation to prenatal perfluoroalkyl substance exposure: The Hokkaido study
Ryu Miura, Atsuko Araki, Chihiro Miyashita, Sumitaka Kobayashi, Sachiko Kobayashi, Shu-Li Wang, Chung-Hsing Chen, Kunio Miyake, Mayumi Ishizuka, Yusuke Iwasaki, Yoichi M. Ito, Takeo Kubota, Reiko Kishi
Environment International, 115, 21, 28, Elsevier Ltd, 2018年06月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Prenatal exposure to perfluoroalkyl substances (PFASs) influences fetal development and later in life. Objective: To investigate cord blood DNA methylation changes associated with prenatal exposure to PFASs. Methods: We assessed DNA methylation in cord blood samples from 190 mother-child pairs from the Sapporo cohort of the Hokkaido Study (discovery cohort) and from 37 mother-child pairs from the Taiwan Maternal and Infant Cohort Study (replication cohort) using the Illumina HumanMethylation 450 BeadChip. We examined the associations between methylation and PFAS levels in maternal serum using robust linear regression models and identified differentially methylated positions (DMPs) and regions (DMRs). Results: We found four DMPs with a false discovery rate below 0.05 in the discovery cohort. Among the top 20 DMPs ranked by the lowest P-values for perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) exposure, four DMPs showed the same direction of effect and P-value <
0.05 in the replication assay: cg16242615 mapped to ZBTB7A, cg21876869 located in the intergenic region (IGR) of USP2-AS1, cg00173435 mapped to TCP11L2, and cg18901140 located in IGR of NTN1. For DMRs, we found a region associated with PFOA exposure with family-wise error rate <
0.1 located in ZFP57, showing the same direction of effect in the replication cohort. Among the top five DMRs ranked by the lowest P-values that were associated with exposure to PFOS and PFOA, in addition to ZFP57, DMRs in the CYP2E1, SMAD3, SLC17A9, GFPT2, DUSP22, and TCERG1L genes showed the same direction of effect in the replication cohort. Conclusion: We suggest that prenatal exposure to PFASs may affect DNA methylation status at birth. Longitudinal studies are needed to examine whether methylation changes observed are associated with differential health outcomes.

Educational system based on the TAPP checklist improves the performance of novices: a multicenter randomized trial
Saseem Poudel, Yo Kurashima, Kimitaka Tanaka, Hiroshi Kawase, Yoichi M. Ito, Fumitaka Nakamura, Toshiaki Shichinohe, Satoshi Hirano
Surgical Endoscopy and Other Interventional Techniques, 32, 5, 2480, 2487, Springer New York LLC, 2018年05月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Despite recent developments in surgical education, obstacles including inadequate budget, limited human resources, and a scarcity of time have limited its widespread adoption. To provide systematic training for laparoscopic inguinal hernia repair, we had previously developed and validated a checklist to evaluate the recorded performance of transabdominal preperitoneal (TAPP) repair. We had also developed an educational system that included didactic materials based on the TAPP checklist and incorporated remote evaluation and feedback system. The aim of this study was to evaluate the educational impact of the TAPP education system on novice surgeons. Methods: Residents and surgeons from participating hospitals, who had performed 0 or 1 TAPP procedure, were randomly assigned to the intervention group (IG), who trained using this new educational tool, and the control group (CG), who trained using the conventional system. Their surgical videos were rated by blinded raters. All participants performed their first case prior to randomization. The primary outcome was improvement of TAPP checklist score from the first to the third case. Results: Eighteen participants from 9 institutes were recruited for this study. Seven participants in the IG and 5 participants in the CG were included in the final analysis. The participants in the IG demonstrated significant improvement in their TAPP performance (p = 0.044) from their first case to their third case, whereas their counterparts in the CG failed to make any significant progress during the same period (p = 0.581). Conclusion: The new TAPP educational system was effective in improving the TAPP performance of novice surgeons.

母親の喫煙およびBMIと小児の喘鳴および湿疹との対照的な関連性(Contrasting associations of maternal smoking and BMI with wheeze and eczema in children)
Goudarzi Houman, Konno Satoshi, Kimura Hirokazu, Araki Atsuko, Miyashita Chihiro, Itou Sachiko, Bamai Yu Ait, Kimura Hiroki, Shimizu Kaoruko, Suzuki Masaru, Ito Yoichi, Nishimura Masaharu, Kishi Reiko
アレルギー, 67, 4-5, 509, 509, (一社)日本アレルギー学会, 2018年05月
英語

Prospective predictors of exacerbation status in severe asthma over a 3-year follow-up
Kimura, H. Department of Respiratory Medicine, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Konno, S. Department of Respiratory Medicine, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Makita, H. Department of Respiratory Medicine, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Taniguchi, N. Department of Respiratory Medicine, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Shimizu, K. Department of Respiratory Medicine, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Suzuki, M. Department of Respiratory Medicine, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Kimura, H. Department of Respiratory Medicine, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Goudarzi, H. Department of Respiratory Medicine, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, Nakamaru, Y. Otolaryngology Head, Neck Surgery, Hokkaido University School of Medicine, Ono, J, Shino-Test Corporation, Ohta, S. Division of, Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, Izuhara, K. Division of, Medical Biochemistry, Department of Biomolecular Sciences, Saga Medical School, M. Ito, Y. Department, of Biostatistics, Faculty of Medicine, Graduate School of Medicine, Hokkaido University, E. Wenzel, S. University of Pittsburgh Asthma, Institute at UPMC, University of Pittsburgh School of Medicine, Nishimura, M. Department of Respiratory Medicine, Faculty of Medicine, Graduate School of Medicine, Hokkaido University
Clinical and Experimental Allergy, 48, 9, 1137, 46, 2018年05月, ［査読有り］
研究論文（学術雑誌）

Effect of combined treatment with bisphosphonate and vitamin D on atherosclerosis in patients with systemic lupus erythematosus: a propensity score-based analysis.
Kazumasa Ohmura, Masaru Kato, Toshiyuki Watanabe, Kenji Oku, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Yoichi M Ito, Norihiro Sato, Tatsuya Atsumi
Arthritis research & therapy, 20, 1, 72, 72, BMC, 2018年04月17日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Premature atherosclerosis is one of the major complications of systemic lupus erythematosus (SLE). Recently, the biological linkage between atherosclerosis and osteoporosis has garnered much attention. The aim of this study is to explore correlation between the development of atherosclerosis and anti-osteoporotic treatment. METHODS: Consecutive patients with SLE (n = 117) who underwent carotid ultrasonography were retrospectively analyzed using propensity scoring. RESULTS: Of the 117 patients, 42 (36%), 27 (23%), and 30 (26%) were receiving bisphosphonates and vitamin D (BP + VD), bisphosphonates alone, or vitamin D alone, respectively. Low bone mineral density was more frequent, and carotid plaque was less prevalent in the BP + VD group compared with other treatment groups. Age (OR = 1.57) and BP + VD treatment (OR = 0.24) were shown by multivariate analysis to be associated with the presence of carotid plaque. In all strata divided using the propensity score, carotid plaque was statistically significantly less prevalent (p = 0.015, Mantel-Haenszel test) in the BP + VD group relative to the other treatment groups. CONCLUSION: Combined treatment with bisphosphonate and vitamin D may have a role in preventing atherosclerosis in patients with SLE.

Effects of dietary supplementation with milk fat globule membrane on the physical performance of community-dwelling Japanese adults: a randomised, double-blind, placebo-controlled trial.
Kokai, Yasuo Department, of Biomedical Engineering, Sapporo Medical University School of Medicine, Mikami, Nana Department, of Biomedical Engineering, Sapporo Medical University School of, Medicine, Tada, Mitsuhiro Department of Neurosurgery, Rumoi Municipal Hospital, Tomonobu, Kazuishi ealth, Care Food, Research Laboratory, Kao Corporation, Ochiai, Ryuji ealth, Care Food, Research Laboratory, Kao Corporation, Osaki, Noriko ealth, Care Food, Research Laboratory, Kao Corporation, Katsuragi, Yoshihisa ealth, Care Food, Research Laboratory, Kao Corporation, Sohma, Hitoshi Department of Educational Development, Sapporo Medical, University Center for Medical Education, Ito, Yoichi M. Department, of Biostatics, Hokkaido University, Graduate School of Medicine
Journal of Nutritional Science., 7, e18, CAMBRIDGE UNIV PRESS, 2018年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, We conducted a randomised, double-blind, placebo-controlled trial to elucidate the effects of dietary milk fat globule membrane (MFGM) on the physical performance of community-dwelling Japanese adults. For this 24-week study, 115 middle-aged subjects (range 50-70 years old) were invited, of whom 113 (seventy-two women, forty-one men) completed the trial. Participants were then divided into either the placebo control or MFGM group. Measurements of physical performance (without undertaking any mandatory exercise) examining muscle strength, agility and balance were tested every 6 weeks until 24 weeks. Analyses were performed using the intention-to-treat method for all participants. Although the effects of MFGM on muscle strength and agility were not significant, we noted that the parameter for balance (such as the ability to stand on one leg with eyes closed for longer durations) increased in the MFGM group (mean 10·1 (95 % CI 8·25, 12·4) s) compared with the placebo (mean 7·53 (95 % CI 6·11, 9·30) s) (P = 0·046). Similarly, application of the mixed-effect model for repeated measures under unstructured covariance also revealed that the effect of MFGM was significant when compared with the placebo (10·2 (95 % CI 8·33, 12·4) v. 7·61 (95 % CI 6·17, 9·30) s) (P = 0·045). In conclusion, we demonstrated that MFGM had an effect on the physical performance of community-dwelling Japanese adults despite mandatory exercise. However, studies using larger cohorts of individuals from different demographic backgrounds are required to further elucidate the mechanisms underlying these effects and to extend the application of MFGM.

LONG-TERM EFFECTS OF ANGIOTENSIN CONVERTING ENZYME INHIBITOR ON LEFT VENTRICULAR EJECTION FRACTION IN DUCHENNE AND BECKER MUSCULAR DYSTROPHY: A LONGITUDINAL CARDIAC MAGNETIC RESONANCE IMAGING STUDY
Tadao Aikawa, Atsuhito Takeda, Noriko Oyama-Manabe, Masanao Naya, Hirokuni Yamazawa, Kazuhiro Koyanagawa, Yoichi M. Ito, Yuka Ishikawa, Yukitoshi Ishikawa, Toshihisa Anzai
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 71, 11, 1565, 1565, ELSEVIER SCIENCE INC, 2018年03月, ［査読有り］
英語

Present developments in reaching an international consensus for a model-based approach to particle beam therapy.
Anussara Prayongrat, Kikuo Umegaki, Arjen van der Schaaf, Albert C Koong, Steven H Lin, Thomas Whitaker, Todd McNutt, Naruhiro Matsufuji, Edward Graves, Masahiko Mizuta, Kazuhiko Ogawa, Hiroyuki Date, Kensuke Moriwaki, Yoichi M Ito, Keiji Kobashi, Yasuhiro Dekura, Shinichi Shimizu, Hiroki Shirato
Journal of radiation research, 59, suppl_1, i72-i76, I76, OXFORD UNIV PRESS, 2018年03月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Particle beam therapy (PBT), including proton and carbon ion therapy, is an emerging innovative treatment for cancer patients. Due to the high cost of and limited access to treatment, meticulous selection of patients who would benefit most from PBT, when compared with standard X-ray therapy (XRT), is necessary. Due to the cost and labor involved in randomized controlled trials, the model-based approach (MBA) is used as an alternative means of establishing scientific evidence in medicine, and it can be improved continuously. Good databases and reasonable models are crucial for the reliability of this approach. The tumor control probability and normal tissue complication probability models are good illustrations of the advantages of PBT, but pre-existing NTCP models have been derived from historical patient treatments from the XRT era. This highlights the necessity of prospectively analyzing specific treatment-related toxicities in order to develop PBT-compatible models. An international consensus has been reached at the Global Institution for Collaborative Research and Education (GI-CoRE) joint symposium, concluding that a systematically developed model is required for model accuracy and performance. Six important steps that need to be observed in these considerations include patient selection, treatment planning, beam delivery, dose verification, response assessment, and data analysis. Advanced technologies in radiotherapy and computer science can be integrated to improve the efficacy of a treatment. Model validation and appropriately defined thresholds in a cost-effectiveness centered manner, together with quality assurance in the treatment planning, have to be achieved prior to clinical implementation.

Assessing the uncertainty in a normal tissue complication probability difference (ΔNTCP): radiation-induced liver disease (RILD) in liver tumour patients treated with proton vs X-ray therapy
Kobashi, Keiji Department of Medical Physics, Hokkaido University Hospital, Prayongrat, Anussara Department of, Radiation Oncology, Graduate School of Medicine, Hokkaido University, Kimoto, Takuya Department, of Radiology, Kyoto Prefectural, University of Medicine, Toramatsu, Chie Department of, Radiation Oncology, Tokyo Women’s Medical University, Dekura, Yasuhiro Department of, Radiation Oncology, Graduate School of Medicine, Hokkaido University, Katoh, Norio Department of, Radiation Oncology, Hokkaido University Hospital, Shimizu, Shinichi Department of, Radiation Oncology, Faculty of Medicine, Hokkaido University, M. Ito, Yoichi Department, of Biostatistics, Faculty of Medicine, Hokkaido University, Shirato, Hiroki Global, Station for, Quantum Biomedical Science, Engineering, Global Institute, for Cooperative Research, Education, Hokkaido University
Journal of Radiation Research, 59, suppl_1, i50, i57, Oxford University Press, 2018年03月01日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Modern radiotherapy technologies such as proton beam therapy (PBT) permit dose escalation to the tumour and minimize unnecessary doses to normal tissues. To achieve appropriate patient selection for PBT, a normal tissue complication probability (NTCP) model can be applied to estimate the risk of treatment-related toxicity relative to X-ray therapy (XRT). A methodology for estimating the difference in NTCP ('NTCP), including its uncertainty as a function of dose to normal tissue, is described in this study using the Delta method, a statistical method for evaluating the variance of functions, considering the variance-covariance matrix. We used a virtual individual patient dataset of radiation-induced liver disease (RILD) in liver tumour patients who were treated with XRT as a study model. As an alternative option for individual patient data, dose-bin data, which consists of the number of patients who developed toxicity in each dose level/bin and the total number of patients in that dose level/bin, are useful for multi-institutional data sharing. It provides comparable accuracy with individual patient data when using the Delta method. With reliable NTCP models, the 'NTCP with uncertainty might potentially guide the use of PBT
however, clinical validation and a cost-effectiveness study are needed to determine the appropriate 'NTCP threshold.

Evaluation of amnion-derived mesenchymal stem cells for treatment-resistant moderate Crohn’s disease: study protocol for a phase I/II, dual-centre, open-label, uncontrolled, dose–response trial
Otagiri, Shinsuke Department of Gastroenterology, Hepatology, Hokkaido, University Graduate School of, Medicine, Ohnishi, Shunsuke Department of Gastroenterology, Hepatology, Hokkaido, University Graduate School of, Medicine, Miura, Arisa Clinical Research, Medical Innovation Center, Hokkaido University, Hospital, Hayashi, Hiroshi Clinical Research, Medical Innovation Center, Hokkaido University Hospital, Kumagai, Izumi Clinical Research, Medical Innovation Center, Hokkaido University Hospital, M. Ito, Yoichi Department, of Biostatistics, Hokkaido University, Graduate School of Medicine, Katsurada, Takehiko Department of Gastroenterology, Hepatology, Hokkaido, University, Graduate School of, Medicine, Nakamura, Shiro Department of Inflammatory Bowel Disease, Hyogo College of, Medicine, Okamoto, Rika Center, for Clinical Research, Education, Hyogo College, of, Medicine, Yamahara, Kenichi Department of Transfusion Medicine, Cell Therapy, Hyogo College of, Medicine, Cho, Kyu Yong, Clinical Research, Medical Innovation Center, Hokkaido University Hospital, Isoe, Toshiyuki Clinical Research, Medical Innovation Center, Hokkaido University Hospital, Sato, Norihiro Clinical Research, Medical Innovation Center, Hokkaido University Hospital, Sakamoto, Naoya Department of Gastroenterology, Hepatology, Hokkaido, University, Graduate School of Medicine
BMJ Open Gastroenterology, 5, 1, e000206, BMJ PUBLISHING GROUP, 2018年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Introduction: The medical treatment options for patients with Crohn's disease (CD) are limited and patients resistant to those therapies are left requiring surgical operations that usually only achieve some symptomatic relief. Mesenchymal stem cells (MSC) have been shown to be effective for the treatment of CD, and we have demonstrated in animal experiments that human amnion-derived MSCs (AMSC) are a potential new therapeutic strategy. Therefore, we designed this study to investigate the safety and efficacy of AMSCs in patients with treatment-resistant CD. Methods and analysis: This is the protocol for an ongoing phase I/II, dual-centre, open-label, uncontrolled, dose-response study. The estimated enrolment is 6-12 patients with treatment-resistant, moderate CD. A dose of 1.0×106 cells/kg will be administered intravenously in the low-dose group at days 0 and 7. After confirming the safety of low-dose administration, a dose of 4.0×106 cells/kg will be administered intravenously in the high-dose group on days 0 and 7. The primary endpoint will measure the occurrence of adverse events related to acute infusion toxicity, and secondary endpoints will include long-term adverse events and efficacy of AMSC administration. Ethics and dissemination: The Institutional Review Board of Hokkaido University Hospital approved this study protocol (approval number H29-6). A report releasing study results will be submitted to an appropriate journal. Discussion: This study is the first to investigate the safety and efficacy of AMSC use for CD treatment. Our results will advance studies on more efficient and convenient methods to overcome the limits of available CD treatments. Trial registration number: UMIN000029841.

Serum periostin is associated with body mass index and allergic rhinitis in healthy and asthmatic subjects
Hirokazu Kimura, Satoshi Konno, Hironi Makita, Natsuko Taniguchi, Hiroki Kimura, Houman Goudarzi, Kaoruko Shimizu, Masaru Suzuki, Noriharu Shijubo, Katsunori Shigehara, Junya Ono, Kenji Izuhara, Yoichi Minagawa Ito, Masaharu Nishimura
Allergology International, 67, 3, 357, 63, Japanese Society of Allergology, 2018年, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Many studies have attempted to clarify the factors associated with serum periostin levels in asthmatic patients. However, these results were based on studies of subjects mainly characterized by high eosinophil counts, which may present as an obstacle for clarification in the identification of other factors associated with serum periostin levels. The aim of this study was to determine the factors associated with serum periostin levels in healthy subjects. We also assessed some factors in asthmatic subjects to confirm their extrapolation for management of asthma. Methods: Serum periostin levels were measured in 230 healthy subjects. Clinical factors of interest included body mass index (BMI) and allergic rhinitis (AR). Additionally, we confirmed whether these factors were associated with serum periostin in 206 asthmatic subjects. We further evaluated several obesity-related parameters, such as abdominal fat distribution and adipocytokine levels. Results: Smoking status, blood eosinophil count, total immunoglobulin E, and the presence of AR were associated with serum periostin in healthy subjects. There was a negative association between BMI and serum periostin in both healthy and asthmatic subjects, while there was a tendency of a positive association with AR in asthmatic subjects. There were no differential associations observed for subcutaneous and abdominal fat in relation to serum periostin in asthmatic subjects. Serum periostin was significantly associated with serum levels of adiponectin, but not with leptin. Conclusions: Our results provided clarity as to the factors associated with serum periostin levels, which could be helpful in the interpretation of serum periostin levels in clinical practice.

Measurement of endometrial thickness in premenopausal women in office gynecology
Hiroshi Tsuda, Yoichi M. Ito, Yukiharu Todo, Takahiro Iba, Keiichi Tasaka, Yuji Sutou, Kozo Hirai, Koichiro Dozono, Yoshifusa Dobashi, Mami Manabe, Tomomi Sakamoto, Ritsu Yamamoto, Katsufumi Ueda, Moe Akatsuka, Yasuhiko Kiyozuka, Nobutaka Nagai, Manami Imai, Koji Kobiki, Hiromasa Fujita, Hiroaki Itamochi, Takafumi Oshita, Takahiro Kawarada, Masayuki Hatae, Yoshihito Yokoyama
Reproductive Medicine and Biology, 17, 1, 29, 35, John Wiley and Sons Ltd, 2018年01月01日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Purpose: To define the median endometrial thickness (ET) in office gynecology is thought to be important for clinical practice. However, there are few reports about ET that have included the general female population on a large scale. The median ET was determined prospectively in premenopausal women who attended office gynecology for cervical cancer screening. Methods: In total, 849 women were enrolled. The median ET was determined by using transvaginal ultrasound and the relationships between the ET and various clinical factors were analyzed. Results: The participants' median age was 38.5 years. The median ET was 8.6 mm (90% and 95% quantiles: 13.8 and 15.8 mm). The ET was not related to their age, symptoms, obstetric history, geographical location, or risk factors for endometrial cancer. In the women with a menstrual cycle length of 28–30 days, the ET was 7 mm on days 1–6, but it increased from 5.4 mm immediately after menstruation (day 7 or 8) to 9.2 mm on days 13–14. Subsequently, the ET increased further to 11.1 mm on day 18. Conclusion: In all the women, the upper limit of the ET was 13.8 mm and 15.8 mm in the 90% and 95% quantile, respectively, in office gynecology.

Distinct phenotypes of smokers with fixed airflow limitation identified by cluster analysis of severe asthma
Satoshi Konno, for the HiCARAT Investigators, Natsuko Taniguchi, Hironi Makita, Yuji Nakamaru, Kaoruko Shimizu, Noriharu Shijubo, Satoshi Fuke, Kimihiro Takeyabu, Mitsuru Oguri, Hirokazu Kimura, Yukiko Maeda, Masaru Suzuki, Katsura Nagai, Yoichi M. Ito, Sally E. Wenzel, Masaharu Nishimura, Akira Isada, Takeshi Hattori, Kenichi Shimizu, Takayuki Yoshida, Kentaro Nagaoka, Shinji Nakane, Yoshiyuki Saito, Tsukasa Sasaki, Hideko Honda, Miho Deai, Ayako Muramoto, Natsumi Kudo, Nozomi Sato, Masanobu Suzuki, Hiroshi Saito, Tetsuya Kojima, Shiho Ichimura, Takashi Choji, Motoko Kobayashi, Akihiko Ishikuro, Yoshihiro Ohtsuka, Fumihiro Honmura, Yasushi Akiyama, Toshiyuki Harada, Akira Kamimura, Norio Tashiro, Hiroshi Mikami, Mistuhide Ohmichi, Yoshitaka Sugawara, Toshiki Takahashi, Makoto Yamamoto, Kei Takamura, Yoshio Tokuchi, Yuji Inoue, Katsunori Shigehara, Hideaki Ukita, Kouki Kikuchi, Hiroyuki Koba, Kyuichirou Sekine, Tsuyoshi Nakano, Yoshihiro Ohata, Noritomo Ohnuma, Fumihiko Sato, Hiroyuki Taguchi, Hiroyuki Sugawara, Osamu Honjo, Seiya Togashi, Hirotaka Nishikiori, Junya Kitada, Masaru Fujii, Eiji Shibuya, Hiroshi Tanaka, Yoshihiro Okamoto, Hiromitu Hiroumi, Kazuhiko Watanabe
Annals of the American Thoracic Society, 15, 1, 33, 41, American Thoracic Society, 2018年01月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Rationale: Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. Objectives: To explore novel severe asthma phenotypes by cluster analysis when including smoking patients with asthma. Methods: We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics.Clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters. Results: Five clinical clusters, including two characterized by low forced expiratory volume in 1 second/forced vital capacity, were identified. When characteristics of smoking subjects in these two clusters were compared, there were marked differences between the two groups: one had high levels of circulating eosinophils, high immunoglobulin E levels, and a high sinus score, and the other was characterized by low levels of the same parameters. Sputum analysis revealed intriguing differences of cytokine/chemokine pattern in these two groups. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 3 years later. Conclusions: This study reveals two distinct phenotypes with potentially different biological pathways contributing to fixed airflow limitation in cigarette smokers with severe asthma.

The effect of duration of illness and antipsychotics on subcortical volumes in schizophrenia: Analysis of 778 subjects.
Naoki Hashimoto, Yoichi M Ito, Naohiro Okada, Hidenaga Yamamori, Yuka Yasuda, Michiko Fujimoto, Noriko Kudo, Ariyoshi Takemura, Shuraku Son, Hisashi Narita, Maeri Yamamoto, Khin Khin Tha, Asuka Katsuki, Kazutaka Ohi, Fumio Yamashita, Shinsuke Koike, Tsutomu Takahashi, Kiyotaka Nemoto, Masaki Fukunaga, Toshiaki Onitsuka, Yoshiyuki Watanabe, Hidenori Yamasue, Michio Suzuki, Kiyoto Kasai, Ichiro Kusumi, Ryota Hashimoto
NeuroImage. Clinical, 17, 563, 569, ELSEVIER SCI LTD, 2018年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: The effect of duration of illness and antipsychotic medication on the volumes of subcortical structures in schizophrenia is inconsistent among previous reports. We implemented a large sample analysis utilizing clinical data from 11 institutions in a previous meta-analysis. Methods: Imaging and clinical data of 778 schizophrenia subjects were taken from a prospective meta-analysis conducted by the COCORO consortium in Japan. The effect of duration of illness and daily dose and type of antipsychotics were assessed using the linear mixed effect model where the volumes of subcortical structures computed by FreeSurfer were used as a dependent variable and age, sex, duration of illness, daily dose of antipsychotics and intracranial volume were used as independent variables, and the type of protocol was incorporated as a random effect for intercept. The statistical significance of fixed-effect of dependent variable was assessed. Results: Daily dose of antipsychotics was positively associated with left globus pallidus volume and negatively associated with right hippocampus. It was also positively associated with laterality index of globus pallidus. Duration of illness was positively associated with bilateral globus pallidus volumes. Type of antipsychotics did not have any effect on the subcortical volumes. Discussion: A large sample size, uniform data collection methodology and robust statistical analysis are strengths of the current study. This result suggests that we need special attention to discuss about relationship between subcortical regional brain volumes and pathophysiology of schizophrenia because regional brain volumes may be affected by antipsychotic medication.

Performance of computed tomography-derived pulmonary vasculature metrics in the diagnosis and haemodynamic assessment of pulmonary arterial hypertension
Kaoruko Shimizu, Ichizo Tsujino, Takahiro Sato, Ayako Sugimoto, Toshitaka Nakaya, Taku Watanabe, Hiroshi Ohira, Yoichi M. Ito, Masaharu Nishimura
EUROPEAN JOURNAL OF RADIOLOGY, 96, 31, 38, ELSEVIER IRELAND LTD, 2017年11月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Few studies have addressed the value of combining computed tomography-derived pulmonary vasculature metrics for the diagnosis and haemodynamic evaluation of pulmonary arterial hypertension (PAH).
Materials and methods: We measured three computed tomography parameters for the pulmonary artery, peripheral vessels, and pulmonary veins: the ratio of the diameter of the pulmonary artery to the aorta (PA/Ao), the cross-sectional area of small pulmonary vessels < 5 mm(2) as a percentage of total lung area (%CSA(<5)), and the diameter of the right inferior pulmonary vein (PVD). The measured quantities were compared between patients with PAH (n = 45) and control subjects (n = 56), and their diagnostic performance and associations with PAH-related clinical indices, including right heart catheterization measurements, were examined.
Results: PA/Ao and %CSA(< 5) were significantly higher in patients with PAH than in controls. Receiver-operating characteristic curve analysis for ability to diagnose PAH showed a high area under the curve (AUC) for PA/Ao (0.95) and modest AUC5 for %CSA(< 5) (0.75) and PVD (0.56). PA/Ao correlated positively with mean pulmonary arterial pressure and PVD correlated negatively with pulmonary vascular resistance. The %CSA(<5) correlated negatively with mean pulmonary arterial pressure and pulmonary vascular resistance and positively with cardiac index. Notably, the PA/Ao and PVD values divided by %CSA(< 5) correlated better with right heart catheterization indices than the non-divided values.
Conclusion: PA/Ao, %CSA(< 5), and PVD are useful non-invasive pulmonary vasculature metrics, both alone and in combination, for diagnosis and haemodynamic assessment of PAH.

Regional interaction between myocardial sympathetic denervation, contractile dysfunction, and fibrosis in heart failure with preserved ejection fraction: 11C-hydroxyephedrine PET study.
Tadao Aikawa, Masanao Naya, Masahiko Obara, Noriko Oyama-Manabe, Osamu Manabe, Keiichi Magota, Yoichi M Ito, Chietsugu Katoh, Nagara Tamaki
European journal of nuclear medicine and molecular imaging, 44, 11, 1897, 1905, SPRINGER, 2017年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: This investigation aimed to identify significant predictors of regional sympathetic denervation quantified by 11C-hydroxyephedrine (HED) positron emission tomography (PET) in patients with heart failure with preserved left ventricular ejection fraction (HFpEF). METHODS: Included in the study were 34 patients (age 63 ± 15 years, 23 men) with HFpEF (left ventricular ejection fraction ≥40%) and 11 age-matched volunteers without heart failure. Cardiac magnetic resonance imaging was performed to measure left ventricular size and function, and the extent of myocardial late gadolinium enhancement (LGE). 11C-HED PET was performed to quantify myocardial sympathetic innervation that was expressed as a 11C-HED retention index (RI, %/min). To identify predictors of regional 11C-HED RI in HFpEF patients, we propose a multivariate mixed-effects model for repeated measures over segments with an unstructured covariance matrix. RESULTS: Global 11C-HED RI was significantly lower and more heterogeneous in HFpEF patients than in volunteers (P < 0.01 for all). Regional 11C-HED RI was correlated positively with systolic wall thickening (r = 0.42, P < 0.001) and negatively with the extent of LGE (r = -0.43, P < 0.001). Segments in HFpEF patients with a large extent of LGE had the lowest regional 11C-HED RI among all segments (P < 0.001 in post hoc tests). Multivariate analysis demonstrated that systolic wall thickening and the extent of LGE were significant predictors of regional 11C-HED RI in HFpEF patients (both P ≤ 0.001). CONCLUSION: Regional sympathetic denervation was associated with contractile dysfunction and fibrotic burden in HFpEF patients, suggesting that regional sympathetic denervation may provide an integrated measure of myocardial damage in HFpEF.

Delayed Gastric Emptying in Side-to-Side Gastrojejunostomy in Pancreaticoduodenectomy: Result of a Propensity Score Matching
Akio Tsutaho, Toru Nakamura, Toshimichi Asano, Keisuke Okamura, Takahiro Tsuchikawa, Takehiro Noji, Yoshitsugu Nakanishi, Kimitaka Tanaka, Soichi Murakami, Yo Kurashima, Yuma Ebihara, Toshiaki Shichinohe, Yoichi M. Ito, Satoshi Hirano
JOURNAL OF GASTROINTESTINAL SURGERY, 21, 10, 1635, 1642, SPRINGER, 2017年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background Delayed gastric emptying (DGE) is one of the most common morbidities of pancreaticoduodenectomy (PD). The aim of this study was to clarify whether the incidence of DGE can be reduced by side-to-side gastric greater curvature-to-jejunal anastomosis in subtotal stomach-preserving pancreaticoduodenectomy (SSPPD).
Methods The clinical data of 253 patients who had undergone PD were examined. Of a total of 188 patients who had undergone SSPPD, a gastrojejunostomy (GJ) was performed with end-to-side anastomosis in 87 patients (SSPPD-ETS group), and a GJ was performed with a greater curvature side-to-jejunal side anastomosis in 101 patients (SSPPD-STS group). After propensity score matching, the matched cohort consisted of 74 patients in each group. The postoperative data were evaluated according to the International Study Group of Pancreatic Surgery grade of DGE.
Results The total incidence of DGE was 9.4% in the SSPPD-ETS group and 4% in the SSPPD-STS group, with no significant difference (p = 0.1902). A significant difference was observed between the two groups in the incidence of DGE grade C (p = 0.0426).
Conclusions The incidence of total DGE was not reduced statistically in the STS group compared with the ETS group, but reduced DGE grade C. Side-to-side anastomosis might be associated with a reduced incidence of DGE grade C.

左室収縮が保持された心不全における11C-HED PETを用いた局所心筋交感神経分布の検討　　　　　　　　　　　　　　　
相川 忠夫, 納谷 昌直, 小原 雅彦, 真鍋 徳子, 真鍋 治, 小梁川 和宏, 孫田 恵一, 伊藤 陽一, 志賀 哲, 加藤 千恵次, 玉木 長良
核医学, 54, Suppl., S174, S174, (一社)日本核医学会, 2017年09月, ［査読有り］
日本語

Local relapse of nasopharyngeal cancer and Voxel-based analysis of FMISO uptake using PET with semiconductor detectors
Yukiko Nishikawa, Koichi Yasuda, Shozo Okamoto, Yoichi M. Ito, Rikiya Onimaru, Tohru Shiga, Kazuhiko Tsuchiya, Shiro Watanabe, Wataru Takeuchi, Yuji Kuge, Hao Peng, Nagara Tamaki, Hiroki Shirato
RADIATION ONCOLOGY, 12, 1, 148, 148, BIOMED CENTRAL LTD, 2017年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Hypoxic cancer cells are thought to be radioresistant and could impact local recurrence after radiotherapy (RT). One of the major hypoxic imaging modalities is [F-18] fluoromisonidazole positron emission tomography (FMISO-PET). High FMISO uptake before RT could indicate radioresistant sites and might be associated with future local recurrence. The predictive value of FMISO-PET for intra-tumoral recurrence regions was evaluated using high-resolution semiconductor detectors in patients with nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT).
Methods: Nine patients with local recurrence and 12 patients without local recurrence for more than 3 years were included in this study. These patients received homogeneous and standard doses of radiation to the primary tumor irrespective of FMISO uptake. The FMISO-PET image before RT was examined via a voxel-based analysis, which focused on the relationship between the degree of FMISO uptake and recurrence region.
Results: In the pretreatment FMISO-PET images, the tumor-to-muscle ratio (TMR) of FMISO in the voxels of the tumor recurrence region was significantly higher than that of the non-recurrence region (p < 0.0001). In the recurrent patient group, a TMR value of 1.37 (95% CI: 1.36-1.39) corresponded to a recurrence rate of 30%, the odds ratio was 5.18 (4.87-5.51), and the area under the curve (AUC) of the receiver operating characteristic curve was 0.613. In all 21 patients, a TMR value of 2.42 (2.36-2.49) corresponded to an estimated recurrence rate of 30%, and the AUC was only 0.591.
Conclusions: The uptake of FMISO in the recurrent region was significantly higher than that in the non-recurrent region. However, the predictive value of FMISO-PET before IMRT is not sufficient for up-front dose escalation for the intra-tumoral high-uptake region of FMISO. Because of the higher mean TMR of the recurrence region, a new hypoxic imaging method is needed to improve the sensitivity and specificity for hypoxia.

Distinct Phenotypes of Smokers with Fixed Airflow Limitation Identified by Cluster Analysis of Severe Asthma.
Konno S, Taniguchi N, Makita H, Nakamaru Y, Shimizu K, Shijubo N, Fuke S, Takeyabu K, Oguri M, Kimura H, Maeda Y, Suzuki M, Nagai K, Ito YM, Wenzel SE, Nishimura M, HiCARAT Investigators
Annals of the American Thoracic Society, 15, 1, 33, 41, AMER THORACIC SOC, 2017年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, RATIONALE: Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. OBJECTIVES: To explore novel severe asthma phenotypes by cluster analysis when including smoking patients with asthma. METHODS: We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters. RESULTS: Five clinical clusters, including two characterized by low forced expiratory volume in 1 second/forced vital capacity, were identified. When characteristics of smoking subjects in these two clusters were compared, there were marked differences between the two groups: one had high levels of circulating eosinophils, high immunoglobulin E levels, and a high sinus score, and the other was characterized by low levels of the same parameters. Sputum analysis revealed intriguing differences of cytokine/chemokine pattern in these two groups. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 3 years later. CONCLUSIONS: This study reveals two distinct phenotypes with potentially different biological pathways contributing to fixed airflow limitation in cigarette smokers with severe asthma.

Changes of Cerebral Oxygenation in Sequential Glenn and Fontan Procedures in the Same Children
Yasunori Yagi, Masataka Yamamoto, Hitoshi Saito, Toshihiro Mori, Yuji Morimoto, Takayoshi Oyasu, Tsuyoshi Tachibana, Yoichi M. Ito
PEDIATRIC CARDIOLOGY, 38, 6, 1215, 1219, SPRINGER, 2017年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Recently, it is common to perform the Fontan procedure after the Glenn procedure as surgical repair for the univentricular heart. How the brain oxygen saturation (rSO(2)) values change with the cardiac restoration and the process of growth during these procedures in individual children remains unknown. In this study, we retrospectively studied rSO(2) data as well as the perioperative clinical records of 30 children who underwent both Glenn and Fontan procedures by the same surgeon in the same institute. The rSO(2) was measured at the beginning and end of each procedure with an INVOS 5100C. Cerebral perfusion pressure was calculated by subtracting central venous pressure from mean arterial pressure. Arterial oxygen saturation (SaO(2)) and the hemoglobin concentration were obtained as candidates affecting rSO(2) changes at the start and the end of both procedures. The rSO(2) increased during the Glenn procedure, but this increase was slight and insignificant. On the other hand, the rSO(2) significantly increased during the Fontan procedure. Significant increases in SaO(2) were observed only between the beginning and end of the Fontan procedure. Correlation coefficients determined by linear regression analysis were more than 0.5 between rSO(2) and SaO(2) in both procedures. Multiple linear regression analysis showed that SaO(2) was the key determinant of the rSO(2). The rSO(2) increases step by step from the Glenn to the Fontan procedure in the same patient. Within each procedure, SaO(2) is the key determinant of the rSO(2). The significance of rSO(2) monitoring in these procedures should be further evaluated.

日本人および米国人患者に対する膀胱全摘除術後周術期死亡予測ノモグラムの外的妥当性の検証
大澤 崇宏, 安部 崇重, 高田 徳容, 伊藤 陽一, 菊地 央, 宮島 直人, 土屋 邦彦, 丸山 覚, Lee Cheryl T., Morgan Todd M., 村井 祥代, 篠原 信雄
泌尿器外科, 30, 7, 1207, 1207, 医学図書出版(株), 2017年07月
日本語

Development of a screening tool to predict malnutrition among children under two years old in Zambia
Junko Hasegawa, Yoichi M. Ito, Taro Yamauchi
GLOBAL HEALTH ACTION, 10, 1, TAYLOR & FRANCIS LTD, 2017年07月, ［査読有り］
英語, 研究論文（学術雑誌）, Background: Maternal and child undernutrition is an important issue, particularly in low-and middle-income countries. Children at high risk of malnutrition should be prioritized to receive necessary interventions to minimize such risk. Several risk factors have been proposed; however, until now, there has been no appropriate evaluation method to identify these children. In sub-Saharan Africa, children commonly receive regular check-ups from community health workers. A simple and easy nutrition assessment method is therefore needed for use by semi-professional health workers.
Objectives: The aim of this study was to develop and test a practical screening tool for community use in predicting growth stunting in children under two years in rural Zambia.
Methods: Field research was conducted from July to August 2014 in Southern Province, Zambia. Two hundred and sixty-four mother-child pairs participated in the study. Anthropometric measurements were performed on all children and mothers, and all mothers were interviewed. Risk factors for the screening test were estimated by using least absolute shrinkage and selection operator analysis. After re-evaluating all participants using the new screening tool, a receiver operating characteristic curve was drawn to set the cut-off value. Sensitivity and specificity were also calculated.
Results: The screening tool included age, weight-for-age Z-score status, birth weight, feeding status, history of sibling death, multiple birth, and maternal education level. The total score ranged from 0 to 22, and the cut-off value was eight. Sensitivity and specificity were 0.963 and 0.697 respectively.
Conclusions: A screening tool was developed to predict children at high risk of malnutrition living in Zambia. Further longitudinal studies are needed to confirm the test's validity in detecting future stunting and to investigate the effectiveness of malnutrition treatment.

A registry study of multiple system atrophy in Hokkaido, Japan: HoRC-MSA Project 2014-16
M. Matsushima, K. Sakushima, I. Yabe, Y. Kanatani, Y. Ito, T. Matsuoka, T. Katayama, H. Uesugi, K. Sako, A. Takei, M. Mori, S. Shimohama, N. Sato, S. Kikuchi, H. Sasaki
MOVEMENT DISORDERS, 32, WILEY, 2017年06月, ［査読有り］
英語

Association between suicide-related ideations and affective temperaments in the Japanese general adult population
Nobuyuki Mitsui, Yukiei Nakai, Takeshi Inoue, Niki Udo, Kan Kitagawa, Yumi Wakatsuki, Rie Kameyama, Atsuhito Toyomaki, Yoichi M. Ito, Yuji Kitaichi, Shin Nakagawa, Ichiro Kusumi
PLOS ONE, 12, 6, e0179952, PUBLIC LIBRARY SCIENCE, 2017年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background
Suicide rates are vastly higher in Japan than in many other countries, although the associations between affective temperaments and suicide-related ideations in the general adult population remain unclear. Therefore, we aimed to elucidate these associations in the present study.
Methods
We analyzed data from 638 Japanese volunteers who completed both the Patient Health Questionnaire (PHQ-9) and the Temperament Evaluation of the Memphis, Pisa, Paris, and San Diego Auto-questionnaire (TEMPS-A). Participants were then divided into three groups based on PHQ-9 summary scores and responses to the suicide-related ideation item: non-depressive control group (NC; N = 469), depressive symptoms without suicide-related ideations group (non-SI; N = 135), and depressive symptoms with suicide-related ideations group (SI; N = 34). The depressive symptoms were defined for PHQ-9 summary scores >= 5, and the suicide-related ideations were defined for PHQ-9 #9 score >= 1. We then compared TEMPS-A scores among the groups using Kruskal-Wallis tests. Then the 95% confidence intervals of differences in TEMPS-A subscale scores between the NC and non-SI groups, or between NC and SI groups, were calculated.
Results
Participants of the SI group exhibited significantly higher scores on the depressive, irritable, and anxious temperament subscales than those of the non-SI group. Similarly, women of the SI group exhibited significantly higher scores of the depressive and irritable temperament subscales than women of the non-SI group, while men of the SI group exhibited significantly higher depressive temperament scores than those of the non-SI group. Among all participants and only men, cyclothymic subscale scores were higher in those of the SI group than the non-SI group (not significant), although the 95% confidence intervals did not overlap.
Limitations
The cross-sectional study design was the main limitation.
Conclusions
Depressive, irritable, and anxious temperaments are significant risk factors for suicide-related ideations in the Japanese general adult population. Furthermore, irritable temperament in women and depressive temperament in men are associated with suicide-related ideations.

Lifetime attributable risk of radiation-induced secondary cancer from proton beam therapy compared with that of intensity-modulated X-ray therapy in randomly sampled pediatric cancer patients
Masaya Tamura, Hideyuki Sakurai, Masashi Mizumoto, Satoshi Kamizawa, Shigeyuki Murayama, Haruo Yamashita, Seishin Takao, Ryusuke Suzuki, Hiroki Shirato, Yoichi M. Ito
JOURNAL OF RADIATION RESEARCH, 58, 3, 363, 371, OXFORD UNIV PRESS, 2017年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, To investigate the amount that radiation-induced secondary cancer would be reduced by using proton beam therapy (PBT) in place of intensity-modulated X-ray therapy (IMXT) in pediatric patients, we analyzed lifetime attributable risk (LAR) as an in silico surrogate marker of the secondary cancer after these treatments. From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: (i) brain, head and neck, (ii) thoracic, (iii) abdominal, and (iv) whole craniospinal (WCNS) irradiation. IMXT was replanned using the same computed tomography and region of interest. Using the dose-volume histograms (DVHs) of PBT and IMXT, the LARs of Schneider et al. were calculated for the same patient. All the published dose-response models were tested for the organs at risk. Calculation of the LARs of PBT and IMXT based on the DVHs was feasible for all patients. The means +/- standard deviations of the cumulative LAR difference between PBT and IMXT for the four categories were (i) 1.02 +/- 0.52% (n = 7, P = 0.0021), (ii) 23.3 +/- 17.2% (n = 8, P = 0.0065), (iii) 16.6 +/- 19.9% (n = 8, P = 0.0497) and (iv) 50.0 +/- 21.1% (n = 3, P = 0.0274), respectively (one tailed t-test). The numbers needed to treat (NNT) were (i) 98.0, (ii) 4.3, (iii) 6.0 and (iv) 2.0 for WCNS, respectively. In pediatric patients who had undergone PBT, the LAR of PBT was significantly lower than the LAR of IMXT estimated by in silico modeling. Although a validation study is required, it is suggested that the LAR would be useful as an in silico surrogate marker of secondary cancer induced by different radiotherapy techniques.

日本人および米国人患者に対する膀胱全摘除術後周術期死亡予測ノモグラムの外的妥当性の検証　　　　　　　　　　　　　　　
大澤 崇宏, 安部 崇重, 高田 徳容, 伊藤 陽一, 菊地 央, 宮島 直人, 土屋 邦彦, 丸山 覚, 村井 祥代, りー・しぇりる, もるがん・とっど, 篠原 信雄
日本泌尿器科学会総会, 105回, OP14, 3, (一社)日本泌尿器科学会総会事務局, 2017年04月
日本語

腸管利用尿路変更膀胱全摘除術における術前因子と周術期重度合併症の関連　　　　　　　　　　　　　　　
山田 修平, 大澤 崇宏, 安部 崇重, 高田 徳容, 伊藤 陽一, 菊池 央, 宮島 直人, 丸山 覚, 土屋 邦彦, 村井 祥代, 篠原 信雄
日本泌尿器科学会総会, 105回, PP11, 08, (一社)日本泌尿器科学会総会事務局, 2017年04月
日本語

Hypoxic glucose metabolism in glioblastoma as a potential prognostic factor.
Takuya Toyonaga, Shigeru Yamaguchi, Kenji Hirata, Kentaro Kobayashi, Osamu Manabe, Shiro Watanabe, Shunsuke Terasaka, Hiroyuki Kobayashi, Naoya Hattori, Tohru Shiga, Yuji Kuge, Shinya Tanaka, Yoichi M Ito, Nagara Tamaki
European journal of nuclear medicine and molecular imaging, 44, 4, 611, 619, SPRINGER, 2017年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: Metabolic activity and hypoxia are both important factors characterizing tumor aggressiveness. Here, we used F-18 fluoromisonidazole (FMISO) and F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) to define metabolically active hypoxic volume, and investigate its clinical significance in relation to progression free survival (PFS) and overall survival (OS) in glioblastoma patients. EXPERIMENTAL DESIGN: Glioblastoma patients (n = 32) underwent FMISO PET, FDG PET, and magnetic resonance imaging (MRI) before surgical intervention. FDG and FMISO PET images were coregistered with gadolinium-enhanced T1-weighted MR images. Volume of interest (VOI) of gross tumor volume (GTV) was manually created to enclose the entire gadolinium-positive areas. The FMISO tumor-to-normal region ratio (TNR) and FDG TNR were calculated in a voxel-by-voxel manner. For calculating TNR, standardized uptake value (SUV) was divided by averaged SUV of normal references. Contralateral frontal and parietal cortices were used as the reference region for FDG, whereas the cerebellar cortex was used as the reference region for FMISO. FDG-positive was defined as the FDG TNR ≥1.0, and FMISO-positive was defined as FMISO TNR ≥1.3. Hypoxia volume (HV) was defined as the volume of FMISO-positive and metabolic tumor volume in hypoxia (hMTV) was the volume of FMISO/FDG double-positive. The total lesion glycolysis in hypoxia (hTLG) was hMTV × FDG SUVmean. The extent of resection (EOR) involving cytoreduction surgery was volumetric change based on planimetry methods using MRI. These factors were tested for correlation with patient prognosis. RESULTS: All tumor lesions were FMISO-positive and FDG-positive. Univariate analysis indicated that hMTV, hTLG, and EOR were significantly correlated with PFS (p = 0.007, p = 0.04, and p = 0.01, respectively) and that hMTV, hTLG, and EOR were also significantly correlated with OS (p = 0.0028, p = 0.037, and p = 0.014, respectively). In contrast, none of FDG TNR, FMISO TNR, GTV, HV, patients' age, or Karnofsky performance scale (KPS) was significantly correlated with PSF or OS. The hMTV and hTLG were found to be independent factors affecting PFS and OS on multivariate analysis. CONCLUSIONS: We introduced hMTV and hTLG using FDG and FMISO PET to define metabolically active hypoxic volume. Univariate and multivariate analyses demonstrated that both hMTV and hTLG are significant predictors for PFS and OS in glioblastoma patients.

Analysis of inter- and intra fractional partial bladder wall movement using implanted fiducial markers
Kentaro Nishioka, Shinichi Shimizu, Nobuo Shinohara, Yoichi M. Ito, Takashige Abe, Satoru Maruyama, Norio Katoh, Rumiko Kinoshita, Takayuki Hashimoto, Naoki Miyamoto, Rikiya Onimaru, Hiroki Shirato
RADIATION ONCOLOGY, 12, 1, 44, 44, BIOMED CENTRAL LTD, 2017年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Current adaptive and dose escalating radiotherapy for muscle invasive bladder cancer requires knowledge of both inter-fractional and intra-fractional motion of the bladder wall involved. The purpose of this study is to characterize inter-and intra-fractional movement of the partial bladder wall using implanted fiducial markers and a real-time tumor-tracking radiotherapy system.
Methods: Two hundred fifty one sessions with 29 patients were analysed. After maximal transurethral bladder tumor resection and 40 Gy of whole bladder irradiation, up to six gold markers were implanted transurethrally into the bladder wall around the tumor bed and used for positional registration. We compared the systematic and random uncertainty of positions between cranial vs. caudal, left vs. right, and anterior vs. posterior tumor groups. The variance in intrafractional movement and the percentage of sessions where 3 mm and 5 mm or more of intrafractional wall movement occurring at 2, 4, 6, 8, 10, and at more than 10 min until the end of a session were determined.
Results: The cranial and anterior tumor group showed larger interfractional uncertainties in the position than the opposite side tumor group in the CC and AP directions respectively, but these differences did not reach significance. Among the intrafractional uncertainty of position, the cranial and anterior tumor group showed significantly larger systematic uncertainty of position than the groups on the opposite side in the CC direction. The variance of intrafractional movement increased over time; the percentage of sessions where intrafractional wall movement was larger than 3 mm within 2 min of the start of a radiation session or larger than 5 mm within 10 min was less than 5%, but this percentage was increasing further during the session, especially in the cranial and anterior tumor group.
Conclusions: More attention for intrafractional uncertainty of position is required in the treatment of cranial and anterior bladder tumors especially in the CC direction. The optimal internal margins in each direction should be chosen or a precise intrafractional target localization system is required depending on the tumor location and treatment delivery time in the setting of partial bladder radiotherapy.

Reduction of HbA1c levels by fucoxanthin-enriched akamoku oil possibly involves the thrifty allele of uncoupling protein 1 (UCP1): A randomised controlled trial in normal-weight and obese Japanese adults
Nana Mikami, Masashi Hosokawa, Kazuo Miyashita, Hitoshi Sohma, Yoichi M. Ito, Yasuo Kokai
Journal of Nutritional Science, 6, e5, Cambridge University Press, 2017年02月14日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Lifestyle-related problems are becoming a major health threat in East Asian countries. Therefore, finding an efficacious nutraceutical for this population is important. One candidate is fucoxanthin (Fx), a carotenoid abundantly found in edible brown seaweed that has been associated with a number of valuable health-promoting benefits. Unfortunately, clinical studies of Fx are limited. In the present study, we aimed to evaluate the effects of Fx on obesity-related parameters in Japanese subjects harbouring an SNP associated with lifestyle-related problems. In all, sixty normal-weight and obese Japanese adults with BMI over 22 kg/m2 were single-blinded and randomly assigned to three Fx-dose cohorts and administered Fx-enriched akamoku oil containing Fx at 0, 1 or 2 mg/d for 8 weeks (n 20 per group). Parameters relating to obesity and serum Fx metabolites were measured before and after intervention, but no significant differences were observed between and within the groups. Despite no changes in visceral fat areas and resting energy expenditures after intervention, we observed a significant decline in HbA1c levels in the 2 mg/d Fx group compared with that in the 0 mg/d group (P <
005), which was correlated with an increase in serum fucoxanthinol (Fx metabolite) levels. In addition, HbA1c levels declined more significantly in subjects with G/G alleles of the uncoupling protein 1 (UCP1) gene than in those with the A/A and A/G alleles (P <
005). We conclude that although Fx supplementation does not affect visceral fat areas, it may reduce HbA1c levels in those harbouring the thrifty allele of UCP1-3826A/G.

Psychometric properties of the Global Operative Assessment of Laparoscopic Skills (GOALS) using item response theory
Yusuke Watanabe, Amin Madani, Yoichi M. Ito, Elif Bilgic, Katherine M. McKendy, Liane S. Feldman, Gerald M. Fried, Melina C. Vassiliou
AMERICAN JOURNAL OF SURGERY, 213, 2, 273, 276, EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC, 2017年02月, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: The extent to which each item assessed using the Global Operative Assessment of Laparoscopic Skills (GOALS) contributes to the total score remains unknown. The purpose of this study was to evaluate the level of difficulty and discriminative ability of each of the 5 GOALS items using item response theory (IRT).
Methods: A total of 396 GOALS assessments for a variety of laparoscopic procedures over a 12-year time period were included. Threshold parameters of item difficulty and discrimination power were estimated for each item using IRT.
Results: The higher slope parameters seen with "bimanual dexterity" and "efficiency" are indicative of greater discriminative ability than "depth perception", "tissue handling", and "autonomy".
Conclusions: IRT psychometric analysis indicates that the 5 GOALS items do not demonstrate uniform difficulty and discriminative power, suggesting that they should not be scored equally. "Bimanual dexterity" and "efficiency" seem to have stronger discrimination. Weighted scores based on these findings could improve the accuracy of assessing individual laparoscopic skills. (C) 2016 Elsevier Inc. All rights reserved.

Accuracy of echocardiographic indices for serial monitoring of right ventricular systolic function in patients with precapillary pulmonary hypertension.
Sato T, Tsujino I, Ohira H, Oyama-Manabe N, Ito YM, Takashina C, Watanabe T, Nishimura M
PloS one, 12, 11, e0187806, PUBLIC LIBRARY SCIENCE, 2017年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Serial assessment of right ventricular ejection fraction (RVEF) predicts the clinical outcome of patients with pulmonary hypertension (PH). Cardiac magnetic resonance imaging (CMRI) enables RVEF monitoring, but its applicability is limited in clinical practice. This study aimed to examine the correlation between changes in CMRI-derived RVEF with those in echocardiographic indices in patients with precapillary PH. METHODS: CMRI and echocardiographic indices of RV systolic function were evaluated at baseline and follow-up in 54 consecutive patients with precapillary PH (pulmonary arterial hypertension (PAH), n = 23; non-PAH, n = 31). During follow-up, medical treatment was optimized according to the guidelines for PH. Using CMRI-derived RVEF as the gold standard, we examined the accuracy of five echocardiographic indices by correlation analysis and receiver operating characteristic (ROC) analysis and by calculating sensitivity, specificity, and positive and negative predictive values. RESULTS: After an average period of 9.5 months, CMRI-derived RVEF improved from 30.2% ± 10.6% at baseline to 41.4% ± 11.3% at follow-up. These changes significantly correlated with those in the five echocardiographic indices, i.e., %RV fractional shortening (r = 0.27), %RV area change (r = 0.46), tricuspid annular plane systolic excursion (TAPSE) (r = 0.84), RV myocardial performance index (RVMPI) (r = -0.72), and systolic lateral tricuspid annular motion velocity (TVlat) (r = 0.66). Of these indices, %RV area change, TAPSE, and TVlat significantly correlated with those of CMRI-derived RVEF in both PAH and non-PAH subgroups. ROC analysis showed that improvement in echocardiographic indices predicted a pre-specified improvement in CMRI-derived RVEF (>2.9%), with TAPSE and TVlat showing better accuracy over the other three indices. CONCLUSIONS: Echocardiographic indices modestly correlate with the changes in CMRI-derived RVEF in precapillary PH patients. Comparison among the five echocardiographic indices revealed that TAPSE and TVlat provide better accuracy than %RV fractional shortening, %RV area change, and RVMPI.

Impact of Real-Time Image Gating on Spot Scanning Proton Therapy for Lung Tumors: A Simulation Study.
Kanehira T, Matsuura T, Takao S, Matsuzaki Y, Fujii Y, Fujii T, Ito YM, Miyamoto N, Inoue T, Katoh N, Shimizu S, Umegaki K, Shirato H
International journal of radiation oncology, biology, physics, 97, 1, 173, 181, ELSEVIER SCIENCE INC, 2017年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Purpose: To investigate the effectiveness of real-time-image gated proton beam therapy for lung tumors and to establish a suitable size for the gating window (GW).
Methods and Materials: A proton beam gated by a fiducial marker entering a preassigned GW (as monitored by 2 fluoroscopy units) was used with 7 lung cancer patients. Seven treatment plans were generated: real-time-image gated proton beam therapy with GW sizes of +/- 1, 2, 3, 4, 5, and 8 mm and free-breathing proton therapy. The prescribed dose was 70 Gy (relative biological effectiveness)/10 fractions to 99% of the target. Each of the 3-dimensional marker positions in the time series was associated with the appropriate 4-dimensional computed tomography phase. The 4-dimensional dose calculations were performed. The dose distribution in each respiratory phase was deformed into the end-exhale computed tomography image. The D99 and D5 to D95 of the clinical target volume scaled by the prescribed dose with criteria of D99 > 95% and D5 to D95 < 5%, V20 for the normal lung, and treatment times were evaluated.
Results: Gating windows <= +/- 2 mm fulfilled the CTV criteria for all patients (whereas the criteria were not always met for GWs >= +/- 3 mm) and gave an average reduction in V20 of more than 17.2% relative to free-breathing proton therapy (whereas GWs >= +/- 4 mm resulted in similar or increased V20). The average (maximum) irradiation times were 384 seconds (818 seconds) for the +/- 1-mm GW, but less than 226 seconds (292 seconds) for the +/- 2-mm GW. The maximum increased considerably at +/- 1-mm GW.
Conclusion: Real-time-image gated proton beam therapy with a GW of +/- 2 mm was demonstrated to be suitable, providing good dose distribution without greatly extending treatment time. (C) 2016 Elsevier Inc. All rights reserved.

ALDH1 and podoplanin expression patterns predict the risk of malignant transformation in oral leukoplakia
Umma Habiba, Kyoko Hida, Tetsuya Kitamura, Aya Yanagawa Matsuda, Fumihiro Higashino, Yoichi M. Ito, Yoichi Ohiro, Yasunori Totsuka, Masanobu Shindoh
ONCOLOGY LETTERS, 13, 1, 321, 328, SPANDIDOS PUBL LTD, 2017年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Oral leukoplakia (OL) is a clinically diagnosed preneoplastic lesion of the oral cavity with an increased oral cancer risk. However, the risk of malignant transformation is still difficult to assess. The objective of the present study was to examine the expression patterns of aldehyde dehydrogenase 1 (ALDH1) and podoplanin in OL, and to determine their roles in predicting oral cancer development. In the present study, the expression patterns of ALDH1 and podoplanin were determined in samples from 79 patients with OL. The association between protein expression and clinicopathological parameters, including oral cancer-free survival, was analyzed during a mean follow-up period of 3.4 years. Expression of ALDH1 and podoplanin was observed in 61 and 67% patients, respectively. Kaplan-Meier analysis demonstrated that the expression of the proteins was correlated with the risk of progression to oral cancer. Multivariate analysis revealed that expression of ALDH1 and podoplanin was associated with 3.02- and 2.62-fold increased risk of malignant transformation, respectively. The malignant transformation risk of OL was considerably higher in cases with expression of both proteins. Point-prevalence analysis revealed that 66% of patients with co-expression of ALDH1 and podoplanin developed oral cancer. Taken together, our data indicate that ALDH1 and podoplanin expression patterns in OL are associated with oral cancer development, suggesting that ALDH1 and podoplanin may be useful biomarkers to identify OL patients with a substantially high oral cancer risk.

Development of a screening tool to predict malnutrition among children under two years old in Zambia
Junko Hasegawa, Yoichi M Ito, Taro Yamauchi
Global Health Action, 10, 1, 1339981, 1339981, Informa UK Limited, 2017年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Maternal and child undernutrition is an important issue, particularly in low- and middle-income countries. Children at high risk of malnutrition should be prioritized to receive necessary interventions to minimize such risk. Several risk factors have been proposed; however, until now, there has been no appropriate evaluation method to identify these children. In sub-Saharan Africa, children commonly receive regular check-ups from community health workers. A simple and easy nutrition assessment method is therefore needed for use by semi-professional health workers. OBJECTIVES: The aim of this study was to develop and test a practical screening tool for community use in predicting growth stunting in children under two years in rural Zambia. METHODS: Field research was conducted from July to August 2014 in Southern Province, Zambia. Two hundred and sixty-four mother-child pairs participated in the study. Anthropometric measurements were performed on all children and mothers, and all mothers were interviewed. Risk factors for the screening test were estimated by using least absolute shrinkage and selection operator analysis. After re-evaluating all participants using the new screening tool, a receiver operating characteristic curve was drawn to set the cut-off value. Sensitivity and specificity were also calculated. RESULTS: The screening tool included age, weight-for-age Z-score status, birth weight, feeding status, history of sibling death, multiple birth, and maternal education level. The total score ranged from 0 to 22, and the cut-off value was eight. Sensitivity and specificity were 0.963 and 0.697 respectively. CONCLUSIONS: A screening tool was developed to predict children at high risk of malnutrition living in Zambia. Further longitudinal studies are needed to confirm the test's validity in detecting future stunting and to investigate the effectiveness of malnutrition treatment.

Lifetime attributable risk of radiation-induced secondary cancer from proton beam therapy compared with that of intensity-modulated X-ray therapy in randomly sampled pediatric cancer patients
Tamura,Masaya, Sakurai,Hideyuki, Mizumoto,Masashi, Kamizawa,Satoshi, Murayama,Shigeyuki, Yamashita,Haruo, Takao,Seishin, Suzuki,Ryusuke, Shirato,Hiroki, Ito,M. Yoichi
J Radiat Res, 58, 3, 363, 371, OXFORD UNIV PRESS, 2016年10月, ［査読有り］
英語, 研究論文（学術雑誌）, To investigate the amount that radiation-induced secondary cancer would be reduced by using proton beam therapy (PBT) in place of intensity-modulated X-ray therapy (IMXT) in pediatric patients, we analyzed lifetime attributable risk (LAR) as an in silico surrogate marker of the secondary cancer after these treatments. From 242 pediatric patients with cancers who were treated with PBT, 26 patients were selected by random sampling after stratification into four categories: (i) brain, head and neck, (ii) thoracic, (iii) abdominal, and (iv) whole craniospinal (WCNS) irradiation. IMXT was replanned using the same computed tomography and region of interest. Using the dose-volume histograms (DVHs) of PBT and IMXT, the LARs of Schneider et al were calculated for the same patient. All the published dose-response models were tested for the organs at risk. Calculation of the LARs of PBT and IMXT based on the DVHs was feasible for all patients. The means ± standard deviations of the cumulative LAR difference between PBT and IMXT for the four categories were (i) 1.02 ± 0.52% (n = 7, P = 0.0021), (ii) 23.3 ± 17.2% (n = 8, P = 0.0065), (iii) 16.6 ± 19.9% (n = 8, P = 0.0497)

Computed tomography (CT)-assessed bronchodilation induced by inhaled indacaterol and glycopyrronium/indacaterol in COPD
Kaoruko Shimizu, Ruriko Seto, Hironi Makita, Masaru Suzuki, Satoshi Konno, Yoichi M. Ito, Rie Kanda, Emiko Ogawa, Yasutaka Nakano, Masaharu Nishimura
RESPIRATORY MEDICINE, 119, 70, 77, W B SAUNDERS CO LTD, 2016年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Our previous studies suggested that the site of bronchodilation on CT might differ between inhaled beta 2 agonists and inhaled anticholinergics in COPD.
Aim: To assess and compare the bronchodilation effects of inhaled indacaterol and glycopyrronium/indacaterol by airway generation in large airways using CT.
Methods: CT scans at full inspiration and pulmonary function tests were done in 25 patients with moderate-severe COPD before and 4-5 weeks after daily inhalation of indacaterol and again another 4-5 weeks after inhalation of glycopyrronium/indacaterol. Airway inner luminal area (Ai) at the 3rd (segmental) to 6th generation of 8 selected bronchi, a total of 32 sites, in the right lung was analyzed on 3 occasions. Our proprietary software enables us to select the same airways and the same measurement sites for comparison, with simultaneous confirmation using two screens on the computer.
Results: The overall increase of Ai (Delta Ai, %) averaged at all 32 measurement sites induced by glycopyrronium/indacaterol had a significant correlation with FEV1 improvement (r = 0.7466, p < 0.0001). Both Delta Ai, % with indacaterol and Delta Ai, % with additional glycopyrronium were significant at the 3rd to 6th generations. Remarkable increases in Delta Ai, % were found at the 5th and 6th generations in several subjects with indacaterol or additional glycopyrronium. There were no significant site-differences in the bronchodilation pattern caused by indacaterol and by glycopyrronium/indacaterol at any of the 3rd to 6th generations.
Conclusions: Additional bronchodilation with glycopyrronium was demonstrated by CT at the 3rd to 6th generations, with no site-specific differences in bronchodilation between indacaterol and glycopyrronium/indacaterol. This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) system (http://www.umin.ac.jp/. ID. UMIN000012043). (C) 2016 Elsevier Ltd. All rights reserved.

Comprehensive assessment of impaired peripheral and coronary artery endothelial functions in smokers using brachial artery ultrasound and oxygen-15-labeled water PET.
Noriki Ochi, Keiichiro Yoshinaga, Yoichi M Ito, Yuuki Tomiyama, Mamiko Inoue, Mutsumi Nishida, Osamu Manabe, Hitoshi Shibuya, Chikara Shimizu, Eriko Suzuki, Satoshi Fujii, Chietsugu Katoh, Nagara Tamaki
Journal of cardiology, 68, 4, 316, 23, ELSEVIER SCIENCE BV, 2016年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Comprehensive evaluation of endothelium-dependent and endothelium-independent vascular functions in peripheral arteries and coronary arteries in smokers has never been performed previously. Through the use of brachial artery ultrasound and oxygen-15-labeled water positron emission tomography (PET), we sought to investigate peripheral and coronary vascular dysfunctions in smokers. METHODS AND RESULTS: Eight smokers and 10 healthy individuals underwent brachial artery ultrasound at rest, during reactive hyperemia [250mmHg cuff occlusion (flow-mediated dilatation (FMD)], and following sublingual nitroglycerin (NTG) administration. Myocardial blood flow (MBF) was assessed through O-15-labeled water PET at rest, during adenosine triphosphate (ATP) administration, and during a cold pressor test (CPT). Through ultrasound, smokers were shown to have significantly reduced %FMD compared to controls (6.62±2.28% vs. 11.29±2.75%, p=0.0014). As assessed by O-15-labeled water PET, smokers were shown to have a significantly lower CPT response than were controls (21.1±9.5% vs. 50.9±16.9%, p=0.0004). There was no relationship between %FMD and CPT response (r=0.40, p=0.097). Endothelium-independent vascular dilatation was similar for both groups in terms of coronary flow reserve with PET (p=0.19). Smokers tended to have lower %NTG in the brachial artery (p=0.055). CONCLUSIONS: Smokers exhibited impaired coronary endothelial function as well as peripheral brachial artery endothelial function. In addition, there was no correlation between PET and ultrasound measurements, possibly implying that while smokers may have systemic vascular endothelial dysfunction, the characteristics of that dysfunction may be different in peripheral arteries and coronary arteries.

Correlation analysis between change in thoracic kyphosis and multilevel facetectomy and screw density in main thoracic adolescent idiopathic scoliosis surgery
Hideki Sudo, Yuichiro Abe, Terufumi Kokabu, Manabu Ito, Kuniyoshi Abumi, Yoichi M. Ito, Norimasa Iwasaki
SPINE JOURNAL, 16, 9, 1049, 1054, ELSEVIER SCIENCE INC, 2016年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND CONTEXT: Controversy exists regarding the effects of multilevel facetectomy and screw density on deformity correction, especially thoracic kyphosis (TK) restoration in adolescent idiopathic scoliosis (AIS) surgery.
PURPOSE: This study aimed to evaluate the effects of multilevel facetectomy and screw density on sagittal plane correction in patients with main thoracic (MT) AIS curve.
STUDY DESIGN: A retrospective correlation and comparative analysis of prospectively collected, consecutive, non-randomized series of patients at a single institution was undertaken.
PATIENT SAMPLE: Sixty-four consecutive patients with Lenke type 1 AIS treated with posterior correction and fusion surgery using simultaneous double-rod rotation technique were included.
OUTCOME MEASURES: Patient demographics and preoperative and 2-year postoperative radiographic measurements were the outcome measures for this study.
METHODS: Multiple stepwise linear regression analysis was conducted between change in TK (T5-T12) and the following factors: age at surgery, Risser sign, number of facetectomy level, screw density, preoperative main thoracic curve, flexibility in main thoracic curve, coronal correction rate, preoperative TK, and preoperative lumbar lordosis. Patients were classified into two groups: TK< 15 degrees group defined by preoperative TK below the mean degree of TK for the entire cohort (< 15 degrees) and the TK >= 15 degrees group, defined by preoperative TK above the mean degree of kyphosis (>= 15 degrees). Independent sample t tests were used to compare demographic data as well as radiographic outcomes between the two groups. There were no study-specific biases related to conflicts of interest.
RESULTS: The average preoperative TK was 14.0 degrees, which improved significantly to 23.1 degrees (p<.0001) at the 2-year final follow-up. Greater change in TK was predicted by a low preoperative TK (p<.0001). The TK < 15 degrees group showed significant correlation between change in TK and number of facetectomy level (r=0.492, p=.002). Similarly, significant correlation was found between change in TK and screw density (r=0.333, p=.047). Conversely, in the TK >= 15 degrees group, correlation was found neither between change in TK and number of facetectomy level (r=0.047, p=.812), nor with screw density (r= 0.030, p=.880). Furthermore, in patients with preoperative TK< 15 degrees, change in TK was significantly correlated with screw density at the concave side (r=0.351, p=.036) but not at the convex side (r=0.144, p=.402).
CONCLUSIONS: In patients with hypokyphotic thoracic spine, significant positive correlation was found between change in TK and multilevel facetectomy or screw density at the concave side. This indicates that in patients with AIS who have thoracic hypokyphosis as part of their deformity, the abovementioned factors must be considered in preoperative planning to correct hypokyphosis. (C) 2016 Elsevier Inc. All rights reserved.

Effects of prenatal exposure to perfluoroalkyl acids on prevalence ofallergic diseases among 4-year-old children
Houman Goudarzi, Chihiro Miyashita, Emiko Okada, Ikuko Kashino, Sumitaka Kobayashi, Chi-Jen Chen, Sachiko Ito, Atsuko Araki, Hideyuki Matsuura, Yoichi M. Ito, Reiko Kishi
ENVIRONMENT INTERNATIONAL, 94, 124, 132, PERGAMON-ELSEVIER SCIENCE LTD, 2016年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Perfluoroalkyl acids (PFAAs) are ubiquitous chemicals extremely resistant and widespread throughout the environment, frequently being detected in human blood samples. Animal studies have revealed that exposure to PFAAs results in immunotoxicity. However, the association between PFAAs, especially long-chain PFAAs, and allergies in humans is not well established. We examined whether prenatal exposure to PFAAs is associated with allergic diseases among 4-year-old children in a large-scale prospective birth cohort in Hokkaido, Japan. In total, 1558 mother-child pairs were included in this study and prenatal levels of eleven PFAAs were measured in maternal plasma samples obtained between 28 and 32 weeks of pregnancy by using ultra-performance liquid chromatography-tandem mass spectrometry. Participant demographic and characteristic information were obtained from self-administered pre- and postnatal questionnaires and medical birth records. Infant allergies were assessed using the Japanese version of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase Three questionnaire, which was administered 4 years post-delivery. Symptoms included eczema, wheezing and rhinoconjunctivitis with a prevalence of 19.0%, 18.7%, and 5.4%, respectively. Associations of PFAA quartiles with allergic outcomes were examined using logistic models. Adjusted odds ratios (ORs) in the 4th quartile vs. 1st quartile (Q4 vs. Q1) for total allergic diseases (including at least one allergic outcome) significantly decreased for perfluorododecanoic acid (PFDoDa) (Q4 vs. Q1 OR: 0.621; 95% confidence interval (CI): 0.454, 0.847) andperfluorotridecanoic acid (PFTrDA) (Q4 vs. Q1 OR: 0.712; 95% CI: 0.524, 0.966) in all children. We obtained similar results when examining the association between PFAAs and eczema. The adjusted OR (Q4 vs. Q1) for wheezing in relation to higher maternal PFHxS levels was 0.728 (95% CI: 0.497, 1.06) in all children. In conclusion, prenatal exposure to long-chain PFAAs, such as PFDoDa and PFTrDA may have an immunosuppressive effect on allergic diseases in 4-year-old children. (C) 2016 Published by Elsevier Ltd.

NTCP modeling analysis of acute hematologic toxicity in whole pelvic radiation therapy for gynecologic malignancies - A dosimetric comparison of IMRT and spot-scanning proton therapy (SSPT)
Takaaki Yoshimura, Rumiko Kinoshita, Shunsuke Onodera, Chie Toramatsu, Ryusuke Suzuki, Yoichi M. Ito, Seishin Takao, Taeko Matsuura, Yuka Matsuzaki, Kikuo Umegaki, Hiroki Shirato, Shinichi Shimizu
PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS, 32, 9, 1095, 1102, ELSEVIER SCI LTD, 2016年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Purpose: This treatment planning study was conducted to determine whether spot scanning proton beam therapy (SSPT) reduces the risk of grade >= 3 hematologic toxicity (HT3+) compared with intensity modulated radiation therapy (IMRT) for postoperative whole pelvic radiation therapy (WPRT).
Methods and materials: The normal tissue complication probability (NTCP) of the risk of HT3+ was used as an in silico surrogate marker in this analysis. IMRT and SSPT plans were created for 13 gynecologic malignancy patients who had received hysterectomies. The IMRT plans were generated using the 7-fields step and shoot technique. The SSPT plans were generated using anterior-posterior field with single field optimization. Using the relative biological effectives (RBE) value of 1.0 for IMRT and 1.1 for SSPT, the prescribed dose was 45 Gy(RBE) in 1.8 Gy(RBE) per fractions for 95% of the planning target volume (PTV). The homogeneity index (HI) and the conformity index (CI) of the PTV were also compared.
Results: The bone marrow (BM) and femoral head doses using SSPT were significantly lower than with IMRT. The NTCP modeling analysis showed that the risk of HT3+ using SSPT was significantly lower than with IMRT (NTCP = 0.04 +/- 0.01 and 0.19 +/- 0.03, p = 0.0002, respectively). There were no significant differences in the CI and HI of the PTV between IMRT and SSPT (CI = 0.97 +/- 0.01 and 0.96 +/- 0.02, p = 0.3177, and HI = 1.24 +/- 0.11 and 1.27 +/- 0.05, p = 0.8473, respectively).
Conclusion: The SSPT achieves significant reductions in the dose to BM without compromising target coverage, compared with IMRT. The NTCP value for HT3+ in SSPT was significantly lower than in IMRT. (C) 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license.

In Vivo Mouse Intervertebral Disc Degeneration Model Based on a New Histological Classification
Takashi Ohnishi, Hideki Sudo, Koji Iwasaki, Takeru Tsujimoto, Yoichi M. Ito, Norimasa Iwasaki
PLOS ONE, 11, 8, e0160486, PUBLIC LIBRARY SCIENCE, 2016年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Although human intervertebral disc degeneration can lead to several spinal diseases, its pathogenesis remains unclear. This study aimed to create a new histological classification applicable to an in vivo mouse intervertebral disc degeneration model induced by needle puncture. One hundred six mice were operated and the L4/5 intervertebral disc was punctured with a 35- or 33-gauge needle. Micro-computed tomography scanning was performed, and the punctured region was confirmed. Evaluation was performed by using magnetic resonance imaging and histology by employing our classification scoring system. Our histological classification scores correlated well with the findings of magnetic resonance imaging and could detect degenerative progression, irrespective of the punctured region. However, the magnetic resonance imaging analysis revealed that there was no significant degenerative intervertebral disc change between the ventrally punctured and non-punctured control groups. To induce significant degeneration in the lumbar intervertebral discs, the central or dorsal region should be punctured instead of the ventral region.

Effects of Multilevel Facetectomy and Screw Density on Postoperative Changes in Spinal Rod Contour in Thoracic Adolescent Idiopathic Scoliosis Surgery
Terufumi Kokabu, Hideki Sudo, Yuichiro Abe, Manabu Ito, Yoichi M. Ito, Norimasa Iwasaki
PLOS ONE, 11, 8, e0161906, PUBLIC LIBRARY SCIENCE, 2016年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Flattening of the preimplantation rod contour in the sagittal plane influences thoracic kyphosis (TK) restoration in adolescent idiopathic scoliosis (AIS) surgery. The effects of multilevel facetectomy and screw density on postoperative changes in spinal rod contour have not been documented. This study aimed to evaluate the effects of multilevel facetectomy and screw density on changes in spinal rod contour from before implantation to after surgical correction of thoracic curves in patients with AIS prospectively. The concave and convex rod shapes from patients with thoracic AIS (n = 49) were traced prior to insertion. Postoperative sagittal rod shape was determined by computed tomography. The angle of intersection of the tangents to the rod end points was measured. Multiple stepwise linear regression analysis was used to identify variables independently predictive of change in rod contour (Delta theta). Average Delta theta at the concave and convex side were 13.6 degrees +/- 7.5 degrees and 4.3 degrees +/- 4.8 degrees, respectively. The Delta theta at the concave side was significantly greater than that of the convex side (P < 0.0001) and significantly correlated with Risser sign (P = 0.032), the preoperative main thoracic Cobb angle (P = 0.031), the preoperative TK angle (P = 0.012), and the number of facetectomy levels (P = 0.007). Furthermore, a Delta theta at the concave side +/- 14 degrees significantly correlated with the postoperative TK angle (P = 0.003), the number of facetectomy levels (P = 0.021), and screw density at the concave side (P = 0.008). Rod deformation at the concave side suggests that corrective forces acting on that side are greater than on the convex side. Multilevel facetectomy and/or screw density at the concave side have positive effects on reducing the rod deformation that can lead to a loss of TK angle postoperatively.

Comparison of conventional ultrasonography and ultrasonography-computed tomography fusion imaging for target identification using digital/real hybrid phantoms: a preliminary study
Takeshi Soyama, Yusuke Sakuhara, Kohsuke Kudo, Daisuke Abo, Jeff Wang, Yoichi M. Ito, Yu Hasegawa, Hiroki Shirato
JOURNAL OF MEDICAL ULTRASONICS, 43, 3, 327, 335, SPRINGER JAPAN KK, 2016年07月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, This preliminary study compared ultrasonography-computed tomography (US-CT) fusion imaging and conventional ultrasonography (US) for accuracy and time required for target identification using a combination of real phantoms and sets of digitally modified computed tomography (CT) images (digital/real hybrid phantoms).
In this randomized prospective study, 27 spheres visible on B-mode US were placed at depths of 3.5, 8.5, and 13.5 cm (nine spheres each). All 27 spheres were digitally erased from the CT images, and a radiopaque sphere was digitally placed at each of the 27 locations to create 27 different sets of CT images. Twenty clinicians were instructed to identify the sphere target using US alone and fusion imaging. The accuracy of target identification of the two methods was compared using McNemar's test. The mean time required for target identification and error distances were compared using paired t tests.
At all three depths, target identification was more accurate and the mean time required for target identification was significantly less with US-CT fusion imaging than with US alone, and the mean error distances were also shorter with US-CT fusion imaging.
US-CT fusion imaging was superior to US alone in terms of accurate and rapid identification of target lesions.

上咽頭癌再発例におけるFMISO-PETと放射線治療に関する解析　　　　　　　　　　　　　　　
安田 耕一, 西川 由記子, 岡本 祥三, 伊藤 陽一, 土屋 和彦, 志賀 哲, 鬼丸 力也, 久下 裕司, 玉木 長良, 白土 博樹
頭頸部癌, 42, 2, 158, 158, (一社)日本頭頸部癌学会, 2016年05月
日本語

Comparison of students' encountered diseases and available diseases at clerkship sites by exploratory multivariate analysis: Are encountered diseases predictable?
Kikuko Taketomi, Makoto Kikukawa, Yoichi M. Ito, Akihiro Yamaoka, Junji Otaki, Motofumi Yoshida
MEDICAL TEACHER, 38, 4, 395, 403, TAYLOR & FRANCIS LTD, 2016年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Students in clerkship are expected to gain clinical expertise by interacting with real patients in clinical situations. Monitoring and predicting the students' encounter diseases (EDs) is important for providing an optimal experience. EDs should be compared with the available diseases (ADs) at the clerkship site and with the required diseases described in some guidelines for the clinical curriculum.
Aims: To explore the differences in ADs as learning resources among different types of clerkship sites and to investigate discrepancies between EDs and ADs.
Method: A retrospective observational study used secondary data from government statistics to compare ADs of various types of observable clerkship sites by biplot analyses, which allowed multivariate comparisons. EDs collected from logbooks during clerkships at a university hospital were also compared with ADs across sites.
Results: The distributions of ADs differed according to institutional type, and EDs at Kyushu University Hospital were similar to the ADs for the category of hospitals in which it was placed.
Conclusion: EDs at a clerkship site may be predictable to some extent by analysing the site's distribution of ADs, but further study is needed. Biplot is useful for visualising these types of statistical similarity.

Comparison of students' encountered diseases and available diseases at clerkship sites by exploratory multivariate analysis: Are encountered diseases predictable? (vol 38, pg 395, 2016)
Kikuko Taketomi, Makoto Kikukawa, Yoichi M. Ito, Akihiro Yamaoka, Junji Otaki, Motofumi Yoshida
MEDICAL TEACHER, 38, 4, 395, 403, TAYLOR & FRANCIS LTD, 2016年04月, ［査読有り］
英語

Nepalese undergraduate nursing students' perceptions of the clinical learning environment, supervision and nurse teachers: A questionnaire survey
Bijeta Nepal, Kikuko Taketomi, Yoichi M. Ito, Masashi Kohanawa, Hidenobu Kawabata, Michiko Tanaka, Junji Otaki
NURSE EDUCATION TODAY, 39, 181, 188, CHURCHILL LIVINGSTONE, 2016年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Clinical practice enables nursing students to acquire essential professional skills, but little is known about nursing students' perceptions of the clinical learning environment (CLE) in Nepal.
Objectives: To examine Nepalese nursing students' perceptions regarding the CLE and supervision.
Design: A cross-sectional questionnaire design was used.
Settings: Government and private hospitals in Nepal where the undergraduate nursing college students undertook their clinical practice.
Participants: Students with clinical practice experience were recruited from years 2-4 of the B.Sc. nursing program in Nepal (n = 350). The final sample comprised 263 students.
Methods: A self-administered questionnaire including demographic characteristics, latest clinical practice site, and general satisfaction was administered February-March 2014. The previously validated Clinical Learning Environment, Supervision and Nurse Teacher evaluation scale was used in the questionnaire. The analytical approach used exploratory factor analysis, assessments of the scale and sub-dimension reliability, correlations of factors between scale sub-dimensions, and multiple regression analysis.
Results: Students' practicum satisfaction level at government hospitals was significantly higher than those at private hospitals (p < 0.0001). Five factors explained 85.7% of the variance, with minor factorial structure differences compared with the original scale. Reliability was confirmed (Cronbach's alpha = 0.93 for total scale, 0.76-0.92 for sub-dimensions). Inter-correlations between the five original sub-dimensions were 0.27-0.68 (p < 0.0001). Students undertaking their practicum in private hospitals evaluated their clinical placements significantly more negatively on most sub-dimensions than those in government hospitals. Multiple regression analysis revealed a significant positive relationship between satisfaction and pedagogical atmosphere (p < 0.0001).
Conclusion: This is the first study to investigate nursing students' perceptions of the CLE in undergraduate nursing programs in Nepal. Students were satisfied with the CLE overall, but satisfaction varied by practicum hospital sector. The most influential factor explaining satisfaction was pedagogical atmosphere. (C) 2016 Elsevier Ltd. All rights reserved.

The clinical trial on the safety and effectiveness of the photodynamic diagnosis of non-muscle-invasive bladder cancer using fluorescent light-guided cystoscopy after oral administration of 5-aminolevulinic acid (5-ALA)
Keiji Inoue, Hideyasu Matsuyama, Kiyohide Fujimoto, Yoshihiko Hirao, Hironobu Watanabe, Seiichiro Ozono, Masafumi Oyama, Munehisa Ueno, Yoshiki Sugimura, Hiroaki Shiina, Hiromitsu Mimata, Haruhito Azuma, Yasushi Nagase, Akio Matsubara, Yoichi M. Ito, Taro Shuin
PHOTODIAGNOSIS AND PHOTODYNAMIC THERAPY, 13, 91, 96, ELSEVIER SCIENCE BV, 2016年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Objective: To examine the utility and safety of photodynamic diagnosis (PDD) after oral administration of 5-aminolevulinic acid (5-ALA) (ALA-PDD) of non-muscle-invasive bladder cancer (NMIBC) using fluorescent-light (FL)-cystoscopy.
Methods: The study was a single-arm, open-label, multi-center prospective study on ALA-PDD of NMIBC, with safety as the primary endpoint and efficacy as the secondary endpoint. Diagnostic potential was evaluated through comparisons with the conventional diagnostic method using a white-light (WL)-source. Clinically recommended doses were also examined. Oral administration of 5-ALA (1.0 g/50 mL) was performed 180-240 min before FL-cystoscopy, and positive or negative results were judged using a WL-source and based on presence or absence of red fluorescence on exposure to a blue FL-source.
Results: Regarding safety, the adverse drug reactions were observed as grade 1 pruritus in 1 patient (0.6%). As for efficacy, specificity and positive predictability were lower than those of a WL-source, but sensitivity was higher with a FL-source than with a WL-source. The proportion of patients with tumors detected only by FL-cystoscopy was greater than the proportion of patients with tumors detected only by conventional WL-cystoscopy. Moreover, not only sensitivity, but also the proportion of patients with tumors detected only by FL-cystoscopy, was highest among patients who received 5-ALA at >= 20 mg/kg/body.
Conclusions: ALA-PDD was shown to be safe and effective. Furthermore, diagnostic accuracy of PDD increased with increased dose of 5-ALA, and the recommended dose was determined as >= 20 mg/kg/body in the present study. (C) 2016 Elsevier B.V. All rights reserved.

Association between Smoking Status and Obesity in a Nationwide Survey of Japanese Adults
Taku Watanabe, Ichizo Tsujino, Satoshi Konno, Yoichi M. Ito, Chisa Takashina, Takahiro Sato, Akira Isada, Hiroshi Ohira, Yoshinori Ohtsuka, Yuma Fukutomi, Hiroyuki Nakamura, Yukio Kawagishi, Chiharu Okada, Nobuyuki Hizawa, Masami Taniguchi, Akira Akasawa, Masaharu Nishimura
PLOS ONE, 11, 3, e0148926, PUBLIC LIBRARY SCIENCE, 2016年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Objective
A positive association between the number of cigarettes smoked per day and obesity has been reported, whereas how other smoking-related indices, such as pack-years and duration of smoking, are related with obesity has been less investigated. We analyzed the age-adjusted cross-sectional association between smoking and obesity in a general Japanese population.
Methods
We used data from a nationwide epidemiological study of Japanese adults (N = 23,106). We compared the prevalence of obesity (defined as body mass index >= 25kg/m(2)) among groups classified by smoking behavior, pack-years, number of cigarettes per day, duration of smoking, and duration and time of smoking cessation.
Results
In men, current smokers had a lower odds ratio (OR) for obesity of 0.80 (95% confidence interval (CI): 0.72-0.88) compared to non-smokers, whereas past smokers had a higher OR of 1.23 (95% CI: 1.09-1.37) compared to current smokers. In women, there were no differences in obesity between the three groups classified by smoking behavior. However, in both sexes, the prevalence of obesity tended to increase with pack-years and the number of cigarettes per day, but not with duration of smoking in current and past smokers. Further, in male smokers, the risks for obesity were markedly higher in short-term heavy smokers compared with long-term light smokers, even with the same number of pack-years. Regarding the impact of smoking cessation, female past smokers who quit smoking at an age > 55-years had an elevated OR of 1.60 (95% CI: 1.05-2.38) for obesity.
Conclusions
In a general Japanese population, obesity is progressively associated with pack-years and number of cigarettes per day, but not with the duration of smoking. When investigating the association between obesity and cigarette smoking, the daily smoking burden and the duration of smoking require to be independently considered.

椎体IMRTとその精度に関する研究　　　　　　　　　　　　　　　
安田 耕一, 清水 伸一, 橋本 孝之, Sutherland Ken, 白土 博樹, 土屋 和彦, 加藤 徳雄, 鬼丸 力也, 木下 留美子, 井上 哲也, 西岡 健太郎, 西川 由記子, 森 崇, 原田 慶一, 原田 八重, 鈴木 隆介, 寅松 千枝, 松浦 妙子, 高尾 聖心, 宮本 直樹, 伊藤 陽一
Japanese Journal of Radiology, 34, Suppl., 5, 5, (公社)日本医学放射線学会, 2016年02月
日本語

Reliable assessment of operative performance
Elif Bilgic, Yusuke Watanabe, Katherine McKendy, Amani Munshi, Yoichi M. Ito, Gerald M. Fried, Liane S. Feldman, Melina C. Vassiliou
AMERICAN JOURNAL OF SURGERY, 211, 2, 426, 430, EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC, 2016年02月, ［査読有り］, ［国際共著］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: There is no consensus regarding the number of intraoperative assessments required to reliably measure trainee performance. This study used generalizability theory (GT) to describe factors contributing to score variance and to estimate the number of assessments needed to achieve high standards of reliability.
METHODS: While performing laparoscopic procedures, trainees were assessed by the attending surgeon using Global Operative Assessment of Laparoscopic Skills (GOALS). Data were collected prospectively (2-month intervals), assessing each trainee multiple times. Reliability coefficient was calculated using trainees, cases, and raters as factors.
RESULTS: Eighteen trainees were included for a total of 65 assessments. Total variance in scores was accounted for as follows: 66.1% by trainees, 31.6% by the interaction between trainees and cases, and 2.3% by raters. At least 3 cases are required for reliable scores using GOALS.
CONCLUSIONS: Trainees accounted for most of the variance in GOALS scores with a minimum of 3 cases required to improve the reliability of the scores obtained. These data may guide the implementation of performance assessments in surgical training programs. (C) 2016 Elsevier Inc. All rights reserved.

Evaluation of the motion of lung tumors during stereotactic body radiation therapy (SBRT) with four-dimensional computed tomography (4DCT) using real-time tumor-tracking radiotherapy system (RTRT)
Keiichi Harada, Norio Katoh, Ryusuke Suzuki, Yoichi M. Ito, Shinichi Shimizu, Rikiya Onimaru, Tetsuya Inoue, Naoki Miyamoto, Hiroki Shirato
PHYSICA MEDICA-EUROPEAN JOURNAL OF MEDICAL PHYSICS, 32, 2, 305, 311, ELSEVIER SCI LTD, 2016年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Purpose: We investigated the usefulness of four-dimensional computed tomography (4DCT) performed before stereotactic body radiation therapy (SBRT) in determining the internal margins for peripheral lung tumors.
Methods and Materials: The amplitude of the movement of a fiducial marker near a lung tumor measured using the maximum intensity projection (MIP) method in 4DCT imaging was acquired before the SBRT (Amp(CT)) and compared with the mean amplitude of the marker movement during SBRT (Amp(mean)) and with the maximum amplitude of the marker movement during SBRT (Amp(max)) using a real-time tumortracking radiotherapy (RTRT) system with 22 patients.
Results: There were no significant differences between the means of the Amp(mean) and the means of the Amp(CT) in all directions (LR, P = 0.45; CC, P = 0.80; AP, P = 0.65). The means of the Amp(max) were significantly larger than the means of the Amp(CT) in all directions (LR, P < 0.01; CC, P = 0.03; AP, P < 0.01). In the lower lobe, the mean difference of the Amp(CT) from the mean of the Amp(max) was 5.7 +/- 8.0 mm, 12.5 +/- 16.7 mm, and 6.8 +/- 8.5 mm in the LR, CC, and AP directions, respectively.
Conclusions: Acquiring 4DCT MIP images before the SBRT treatment is useful to establish the mean amplitude for a patient during SBRT but it underestimates the maximum amplitude during actual SBRT. Caution must be paid to determine the margin with the 4DCT especially for tumors at the lower lobe where it is of the potentially greatest benefit. (C) 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd.

The Association between Prenatal Yoga and the Administration of Ritodrine Hydrochloride during Pregnancy: An Adjunct Study of the Japan Environment and Children's Study.
Kawanishi Y, Saijo Y, Yoshioka E, Nakagi Y, Yoshida T, Miyamoto T, Sengoku K, Ito Y, Miyashita C, Araki A, Kishi R
PloS one, 11, 6, e0158155, 2016年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, INTRODUCTION: While the beneficial effects of prenatal yoga have been reported in recent years, little is known about its effectiveness in pregnant Japanese women. Despite several adverse effects, ritodrine hydrochloride is frequently prescribed to suppress preterm labor in Japan, and its usage may therefore indicate cases of preterm labor. This study aimed to clarify the association between prenatal yoga and ritodrine hydrochloride use during pregnancy. METHODS: An observational study was conducted as an adjunct study by the Hokkaido unit of the Japan Environment and Children's Study. Information on prenatal yoga practice was collected using a self-questionnaire between March 21, 2012, and July 7, 2015, targeting women who had recently delivered. Ritodrine hydrochloride use was identified from medical records. A total of 2,692 women were analyzed using logistic regression models that adjusted for possible confounders. RESULTS: There were 567 (21.1%) women who practiced prenatal yoga, which was associated with a lower risk of ritodrine hydrochloride use (adjusted odds ratio [OR] 0.77; 95% CI 0.61-0.98). This was especially evident in women with a total practice duration that exceeded 900 minutes throughout their pregnancy (adjusted OR 0.54; 95% CI 0.38-0.76). A sensitivity analysis that excluded patients with threatened abortion during the study period produced similar results. CONCLUSIONS: Prenatal yoga was associated with a lower risk of ritodrine hydrochloride use, particularly in women with more than 900 minutes of practice time over the course of their pregnancy. Prenatal yoga may be a beneficial option for pregnant women in the selection of alternative therapies.

The effect of APOE ϵ4 allele on brain perfusion SPECT in late onset Alzheimer's disease by an automated program, 3DSRT
Seiju Kobayashi, Takao Ishii, Masaru Tateno, Hitoshi Sohma, Yasuo Kokai, Yoichi M. Ito, Tomo Iwamoto, Kengo Furuse, Hanako Tsujino, Hidetoshi Morii, Wataru Ukai, Eri Hashimoto, Kumiko Utsumi, Chiaki Kawanishi
Neuropsychiatry, 6, 2, 55, 63, Future Medicine Ltd., 2016年, ［査読有り］
英語, 研究論文（学術雑誌）, Aim: The Apolipoprotein E (APOE) ϵ4 allele is a risk factor for developing Alzheimer's disease (AD), however its impact on cerebral functional changes in AD remains controversial. Previous studies reported conflicting results or failed to confirm any association, possibly because they failed to consider either the effect of patient age at onset or that of clinical stage. We performed functional neuroimaging studies using current improved techniques to re-examine the effect of APOE ϵ4 allele, taking both the age at onset and clinical stage into account. Methods: 111 late onset AD (LOAD) subjects were divided into 3 subgroups based on Clinical Dementia Rating (CDR). We investigated the influence of ϵ4 allele on functional cerebral changes in each group of LOAD by using cutting-edge analysis software, 3DSRT. Results: The APOE ϵ4 allele was significantly associated with relatively preserved cerebral blood flow in the cerebral cortices. The influence of APOE ϵ4 allele is not apparent in the mild stage, but is significantly demonstrable in the moderate stage. Conclusion: Dividing AD subjects into subgroups based on the severity as well as the age at onset is important for precise outcomes. This study may help resolve the uncertainties of previous studies which reported conflicting results or failed to confirm any association. We believe this is the first study focused on the effect of APOE ϵ4 allele on functional cerebral changes at each stage of AD.

Characteristics of Diffusional kurtosis in chronic ischemia of adult Moyamoya disease: Comparing Diffusional kurtosis and diffusion tensor imaging
Kazumata K, Tha K.K, Narita H, Ito Y.M, Shichinohe H, Ito M, Uchino H, Abumiya T
American Journal of Neuroradiology, 37, 8, 1432, 1439, 2016年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND AND PURPOSE: Detecting microstructural changes due to chronic ischemia potentially enables early identification of patients at risk of cognitive impairment. In this study, diffusional kurtosis imaging and diffusion tensor imaging were used to investigate whether the former provides additional information regarding microstructural changes in the gray and white matter of adult patients with Moyamoya disease. MATERIALS AND METHODS: MR imaging (diffusional kurtosis imaging and DTI) was performed in 23 adult patients with Moyamoya disease and 23 age-matched controls. Three parameters were extracted from diffusional kurtosis imaging (mean kurtosis, axial kurtosis, and radial kurtosis), and 4, from DTI (fractional anisotropy, radial diffusivity, mean diffusivity, and axial diffusivity). Voxelwise analysis for these parameters was performed in the normal-appearing brain parenchyma. The association of these parameters with neuropsychological performance was also evaluated. RESULTS: Voxelwise analysis revealed the greatest differences in fractional anisotropy, followed, in order, by radial diffusivity, mean diffusivity, and mean kurtosis. In patients, diffusional kurtosis imaging parameters were decreased in the dorsal deep white matter such as the corona radiata and superior longitudinal fasciculus (P < .01), including areas without DTI abnormality. Superior longitudinal fasciculus fiber-crossing areas showed weak correlations between diffusional kurtosis imaging and DTI parameters compared with tissues with a single-fiber direction (eg, the corpus callosum). Diffusional kurtosis imaging parameters were associated with general intelligence and frontal lobe performance. CONCLUSIONS: Although DTI revealed extensive white matter changes, diffusional kurtosis imaging additionally demonstrated microstructural changes in ischemia-prone deep white matter with abundant fiber crossings. Thus, diffusional kurtosis imaging may be a useful adjunct for detecting subtle chronic ischemic injuries.

Associations among the plasma amino acid profile, obesity, and glucose metabolism in Japanese adults with normal glucose tolerance
Chisa Takashina, Ichizo Tsujino, Taku Watanabe, Shinji Sakaue, Daisuke Ikeda, Asuka Yamada, Takahiro Sato, Hiroshi Ohira, Yoshinori Otsuka, Noriko Oyama-Manabe, Yoichi M. Ito, Masaharu Nishimura
NUTRITION & METABOLISM, 13, 5, 5, BIOMED CENTRAL LTD, 2016年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Amino acids (AAs) are emerging as a new class of effective molecules in the etiology of obesity and diabetes mellitus. However, most investigations have focused on subjects with obesity and/or impaired glucose regulation; the possible involvement of AAs in the initial phase of glucose dysregulation remains poorly understood. Furthermore, little attention has been given to possible associations between the pattern/degree of fat deposition and the plasma AA profile. Our objective was therefore to determine the relationships between plasma AA concentrations and the type/degree of obesity and glucose regulation in Japanese adults with normal glucose tolerance.
Methods: Eighty-three subjects with normal glucose tolerance were classified as obese or nonobese and as visceral obesity or nonvisceral obesity. Correlations between the plasma levels of 23 AAs and somatometric measurements, visceral fat area (VFA), subcutaneous fat area (SFA), and 75-g oral glucose tolerance test results were analyzed.
Results: Obesity or visceral obesity was associated with higher levels of branched-chain AAs (isoleucine, leucine, and valine), lysine, tryptophan, cystine, and glutamate but lower levels of asparagine, citrulline, glutamine, glycine, and serine (p < 0.04). Age-and gender-adjusted analyses indicated that VFA was positively correlated with tryptophan and glutamate levels, whereas VFA and SFA were negatively correlated with citrulline, glutamine, and glycine levels (p < 0.05). The fasting and 2-h plasma glucose levels or the homeostasis model assessment of insulin resistance were positively correlated with valine, glutamate, and tyrosine levels but negatively correlated with citrulline, glutamine, and glycine levels. The homeostasis model assessment for the beta-cell function index was positively correlated with leucine, tryptophan, valine, and glutamate levels but negatively correlated with citrulline, glutamine, glycine, and serine levels (p < 0.05).
Conclusions: The present study identified specific associations between 10 AAs and the type/degree of obesity, and indices of glucose/insulin regulation, in Japanese adults with preserved glucose metabolism. With the growing concern about the increasing prevalence of obesity and diabetes, the possible roles of these AAs as early markers and/or precursors warrant further investigation.

Distinct phenotypes of cigarette smokers identified by cluster analysis of patients with severe asthma
Satoshi Konno, Natsuko Taniguchi, Hironi Makita, Yuji Nakamaru, Kaoruko Shimizu, Noriharu Shijubo, Satoshi Fuke, Kimihiro Takeyabu, Mitsuru Oguri, Hirokazu Kimura, Yukiko Maeda, Masaru Suzuki, Katsura Nagai, Yoichi M. Ito, Sally E. Wenzel, Masaharu Nishimura
Annals of the American Thoracic Society, 12, 12, 1771, 1780, American Thoracic Society, 2015年12月01日, ［査読有り］
英語, 研究論文（学術雑誌）, Rationale: Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. Objectives: To explore novel severe asthma phenotypes by cluster analysis when including cigarette smokers. Methods: We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Twelve clinical variables obtained during a 2-day hospital staywere used for cluster analysis. After clustering using clinical variables, the sputum levels of 14moleculeswere measured to biologically characterize the clinical clusters. Measurements and Main Results: Five clinical clusters were identified, including two characterized by high pack-year exposure to cigarette smoking and low FEV1/FVC. There were marked differences between the two clusters of cigarette smokers. One had high levels of circulating eosinophils, high IgE levels, and a high sinus disease score. The other was characterized by low levels of the same parameters. Sputum analysis revealed increased levels of IL-5 in the former cluster and increased levels of IL-6 and osteopontin in the latter. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 1 year later. Conclusions: This study reveals two distinct phenotypes of severe asthma in current and former cigarette smokers with potentially different biological pathways contributing to fixed airflow limitation.

Distinct Phenotypes of Cigarette Smokers Identified by Cluster Analysis of Patients with Severe Asthma.
Konno S, Taniguchi N, Makita H, Nakamaru Y, Shimizu K, Shijubo N, Fuke S, Takeyabu K, Oguri M, Kimura H, Maeda Y, Suzuki M, Nagai K, Ito YM, Wenzel SE, Nishimura M, Hi-CARAT Investigators
Annals of the American Thoracic Society, 12, 12, 1771, 1780, AMER THORACIC SOC, 2015年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, RATIONALE: Smoking may have multifactorial effects on asthma phenotypes, particularly in severe asthma. Cluster analysis has been applied to explore novel phenotypes, which are not based on any a priori hypotheses. OBJECTIVES: To explore novel severe asthma phenotypes by cluster analysis when including cigarette smokers. METHODS: We recruited a total of 127 subjects with severe asthma, including 59 current or ex-smokers, from our university hospital and its 29 affiliated hospitals/pulmonary clinics. Twelve clinical variables obtained during a 2-day hospital stay were used for cluster analysis. After clustering using clinical variables, the sputum levels of 14 molecules were measured to biologically characterize the clinical clusters. MEASUREMENTS AND MAIN RESULTS: Five clinical clusters were identified, including two characterized by high pack-year exposure to cigarette smoking and low FEV1/FVC. There were marked differences between the two clusters of cigarette smokers. One had high levels of circulating eosinophils, high IgE levels, and a high sinus disease score. The other was characterized by low levels of the same parameters. Sputum analysis revealed increased levels of IL-5 in the former cluster and increased levels of IL-6 and osteopontin in the latter. The other three clusters were similar to those previously reported: young onset/atopic, nonsmoker/less eosinophilic, and female/obese. Key clinical variables were confirmed to be stable and consistent 1 year later. CONCLUSIONS: This study reveals two distinct phenotypes of severe asthma in current and former cigarette smokers with potentially different biological pathways contributing to fixed airflow limitation. Clinical trial registered with www.umin.ac.jp (000003254).

Quantitative evaluation of gait ataxia by accelerometers
Shinichi Shirai, Ichiro Yabe, Masaald Matsushima, Yoichi M. Ito, Mitsuru Yoneyama, Hidenao Sasaki
JOURNAL OF THE NEUROLOGICAL SCIENCES, 358, 1-2, 253, 258, ELSEVIER SCIENCE BV, 2015年11月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, An appropriate biomarker for spinocerebellar degeneration (SCD) has not been identified. Here, we performed gait analysis on patients with pure cerebellar type SCD and assessed whether the obtained data could be used as a neurophysiological biomarker for cerebellar ataxia. We analyzed 25 SCD patients, 25 patients with Parkinson's disease as a disease control, and 25 healthy control individuals. Acceleration signals during 6 min of walking and 1 min of standing were measured by two sets of triaxial accelerometers that were secured with a fixation vest to the middle of the lower and upper back of each subject. We extracted two gait parameters, the average and the coefficient of variation of motion trajectory amplitude, from each acceleration component. Then, each component was analyzed by correlation with the Scale for the Assessment and Rating of Ataxia (SARA) and the Berg Balance Scale (BBS). Compared with the gait control of healthy subjects and concerning correlation with severity and disease specificity, our results suggest that the average amplitude of medial-lateral (upper back) of straight gait is a physiological biomarker for cerebellar ataxia. Our results suggest that gait analysis is a quantitative and concise evaluation scale for the severity of cerebellar ataxia. (C) 2015 Elsevier B.V. All rights reserved.

Reliable Assessment of Performance in Surgery: A Practical Approach to Generalizability Theory
Elif Bilgic, Yusuke Watanabe, Katherine M. McKendy, Yoichi Ito, Melina C. Vassiliou
JOURNAL OF SURGICAL EDUCATION, 72, 5, 774, 775, ELSEVIER SCIENCE INC, 2015年09月, ［査読有り］, ［国際共著］
英語

Regional bronchodilator response assessed by computed tomography in chronic obstructive pulmonary disease
Kaoruko Shimizu, Hironi Makita, Masaru Hasegawa, Hirokazu Kimura, Satoshi Fuke, Katsura Nagai, Takayuki Yoshida, Masaru Suzuki, Satoshi Konno, Yoichi M. Ito, Masaharu Nishimura
EUROPEAN JOURNAL OF RADIOLOGY, 84, 6, 1196, 1201, ELSEVIER IRELAND LTD, 2015年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background and objective: The reliability of CT assessment of regional bronchodilation is not universally accepted. In this study, using our proprietary 3D-CT software, we first examined airway inner luminal area (Ai) before and after inhalation of SFC in a group of COPD patients and then evaluated the same parameters for two sets of CT data obtained from clinically stable subjects with no intervention.
Methods: We conducted CT at deep inspiration and pulmonary function tests before and one week after inhalation of SFC in 23 COPD patients. As a non-intervention group, we used two sets of CT data obtained with one-year interval in another group of subjects who demonstrated stable pulmonary function (n=8). We measured Ai at the mid-portions of 3rd to 6th generation in 8 bronchi of the right lung, a total of 32 identical sites before and after intervention.
Results: The average bronchodilation at all sites (Delta Ai%: 28.2 + 4.1 (SE)%) (r= 0.65, p < 0.001) and that of each generation significantly correlated with % improvement of FEV1 (Delta FEV1%), which increased from 1.40 +/- 0.10L to 1.58 +/- 0.10L. When subjects were classified into two groups in terms of mean Delta FEV1%, even the poor responders (Delta FEV1% <14% above baseline, n=13) displayed significantly larger Delta Ai% compared with the non-intervention group (19.1 +/- 4.6% versus 2.1 +/- 3.9%). Inter-observer variability for overall AAi% was within acceptable levels.
Conclusions: CT can reliably detect the regional bronchodilation in 3rd to 6th generation airways when Delta FEV1 is as small as 180 ml on average. This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) system (http://www.umin.ac.jp/No. UMIN 000002668). (C) 2015 Elsevier Ireland Ltd. All rights reserved.

被験者組入れ不良により中止された介入研究の失敗要因分析 事例検討
佐久嶋 研, 堀江 奈穂, 天野 虎次, 茂木 祐子, 西村 千佳子, 重松 明男, 大庭 幸治, 伊藤 陽一, 佐藤 典宏
薬理と治療, 43, Suppl.1, s94, s98, ライフサイエンス出版(株), 2015年05月
日本語, わが国では近年の治験・臨床研究の体制整備に伴い、アカデミアによる研究支援体制(academic research organization:ARO)に大きな役割が求められつつある。しかし、実際にAROが支援した臨床研究において、被験者組入れが進まないことにより中止となってしまう事例が存在する。そこで、われわれは北海道大学病院がAROとして支援した研究で被験者組入れ不良により中止となった臨床研究の事例分析を行った。事例は、多発性骨髄腫に対するボルテゾミブを中心とした化学療法に関する2つの多施設共同の介入研究とした。分析の内容はAROとして支援した内容のレビューと運営関係者に対するインタビューとした。臨床研究の被験者組入れにおけるマネジメントにおいて考慮すべき要因として、1)主任研究者、2)事務局の構成と役割分担、3)共同研究者・施設、4)プロトコル設計、5)研究マネジメント、の5つの要因が明らかとなった。今後の適切な研究支援体制を構築するために、研究マネジメントにて考慮すべき要因が明らかとなったことから、今後の研究支援に活用していくことが重要である。(著者抄録)

FDG PET performed at thyroid remnant ablation has a higher predictive value for long-term survival of high-risk patients with well-differentiated thyroid cancer than radioiodine uptake.
Florian C Gaertner, Shozo Okamoto, Tohru Shiga, Yoichi M Ito, Yuko Uchiyama, Osamu Manabe, Naoya Hattori, Nagara Tamaki
Clinical nuclear medicine, 40, 5, 378, 83, LIPPINCOTT WILLIAMS & WILKINS, 2015年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: The predictive value of FDG PET at thyroid remnant ablation was evaluated in comparison to radioiodine uptake in high-risk patients with differentiated thyroid cancer. PATIENTS AND METHODS: One hundred forty-one patients who underwent radioiodine therapy (RIT) after total thyroidectomy and received at least 1 further RIT due to suspected metastases were retrospectively analyzed. Patients had not received RIT previously. FDG PET was performed before thyroid remnant ablation. Thyroid-stimulating hormone-stimulated serum thyroglobulin (Tg) was measured for biochemical response assessment (change of Tg between the first and second RIT, ΔTg). RESULTS: Biochemical response could be evaluated in 80 patients; survival data could be obtained for 88 patients (maximum, 124 months). Biochemical response was significantly better in patients with radioiodine-positive metastases compared with patients with radioiodine-negative metastases (median ΔTg I+, 55.8% vs I-, 112.6%; P < 0.01). Regarding survival, deaths occurred later in patients with radioiodine-positive metastases compared with radioiodine-negative patients; however, there was no significant difference regarding overall survival (I+, 61.3% vs I-, 58.2%; P > 0.05). Patients with FDG-positive metastases at thyroid remnant ablation showed a poorer biochemical response compared with patients with FDG-negative metastases (median ΔTg FDG+, 77.5% vs FDG-, 53.2%; P < 0.05), and these groups also differed significantly regarding survival (overall survival FDG+, 48.5% vs FDG-, 100%, P < 0.05). CONCLUSIONS: At thyroid remnant ablation, FDG PET is more predictive for long-term survival, whereas radioiodine uptake is more important for short-term response. FDG PET performed at thyroid remnant ablation might represent a useful tool for management of high-risk patients with differentiated thyroid cancer.

Differential changes in quality of life components over 5 years in chronic obstructive pulmonary disease patients
Katsura Nagai, Hironi Makita, Masaru Suzuki, Kaoruko Shimizu, Satoshi Konno, Yoichi M Ito, Masaharu Nishimura, On behalf of the Hokkaido COPD Cohort Study Investigators, Yoshikazu Kawakami, Youichi Nishiura, Hiroshi Saito, Tetsuya Kojima, Takeshi Igarashi, Kiyonobu Kimura, Ikuo Nakano, Moto Katabami, Kouichi Itabashi, Kiyoshi Morikawa, Seiichi Tagami, Yoshihiro Otsuka, Rika Sato, Junichiro Kojima, Shinji Nigawara, Takashi Morioka, Ichiro Sakai, Hiroshi Yamamoto, Shigeaki Ogura, Kenji Akie, Fumihiro Honmura, Shinichi Kusudou, Hiroshi Izumi, Kensuke Baba, Hiroki Goya, Tsuyoshi Nakano, Kimihiro Takeyabu, Yasushi Akiyama, Fujiya Kishi, Akihide Ito, Michihiro Fujino, Masashi Ohe, Toshiyuki Harada, Akira Kamimura, Nobuyuki Hakuma, Noriaki Sukou, Kazuo Takaoka, Isamu Doi, Atsushi Ishimine, Ryouji Nakano, Yasushi Hasegawa, Yasuyuki Nasuhara, Tomoko Betsuyaku, Kunio Hamada, Yoko Ito, Motoko Kobayashi, Takeshi Hosokawa, Satoshi Fuke, Masaru Hasegawa, Nao Odajima, Chinatsu Moriyama, Takayuki Yoshida, Takashi Inomata, Kanako Maki, Eiji Shibuya, Tsukasa Sasaki, Katsuaki Nitta, Masafumi Yamamoto, Shigetaka Mizuno, Kenji Miyamoto, Nobuyuki Hizawa
International Journal of COPD, 10, 745, 757, Dove Medical Press Ltd., 2015年04月13日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: The aim of the study was to examine the longitudinal change in quality of life components of patients with chronic obstructive pulmonary disease (COPD). Methods: In the Hokkaido COPD Cohort Study, 261 subjects were appropriately treated and followed over 5 years with a 74% follow-up rate at the end. The longitudinal changes in St George’s Respiratory Questionnaire (SGRQ) scores were annually evaluated with forced expiratory volume in 1 second (FEV1). The subjects were classified into the rapid decliners, slow decliners, and sustainers based on ΔFEV1/year. Results: The activity component of SGRQ generally deteriorated over time, and its annual decline was the greatest in the rapid decliners (<
25th percentile). In contrast, the symptom component improved significantly year by year in the sustainers (>
75 percentile), and it did not deteriorate even in the rapid decliners. Of the baseline data, predictors for worsening of the activity component were older age and lower body mass index. Larger reversibility was related to symptom component improvement. Of the follow-up data, ΔFEV1/year was the best predictor for worsening of the components of SGRQ. Continuous smoking was another factor for worsening of the activity component. For the symptom component, a history of exacerbation by admission definition was the determinant of its deterioration, whereas use of beta agonists was related to improvement. Conclusion: The longitudinal changes of quality of life and their determinants are markedly different and independent between its components. The activity component of SGRQ generally deteriorated over years, while the symptom component rather improved in some patients with COPD under appropriate treatment.

Right atrial volume and reservoir function are novel independent predictors of clinical worsening in patients with pulmonary hypertension
Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Noriko Oyama-Manabe, Yoichi M. Ito, Asuka Yamada, Daisuke Ikeda, Taku Watanabe, Masaharu Nishimura
JOURNAL OF HEART AND LUNG TRANSPLANTATION, 34, 3, 414, 423, ELSEVIER SCIENCE INC, 2015年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Symptoms and signs and indices of right heart function are predictors of clinical outcomes in patients with pulmonary hypertension (PH). However, the significance of right atrial (RA) indices has not been sufficiently investigated. We investigated whether RA parameters predict outcomes in patients with pre-capillary PH.
METHODS: Study subjects were 68 patients with pre-capillary PH. RA size and function (systolic, reservoir, and conduit functions) were evaluated by cardiac magnetic resonance imaging.
RESULTS: During the mean follow-up period of 24 months, 16 of 68 patients experienced clinical worsening (CW), defined as hospitalization because of right heart failure, lung transplantation, or PHrelated death. Kaplan-Meier and log-rank test showed that World Health Organization functional class, pericardial effusion, increased brain natriuretic peptide concentration, reduced right ventricular ejection fraction (RVEF), increased minimum RA volume index, and decreased RA reservoir volume were associated with CW-free survival. The combination of RVEF and RA reservoir function was a better predictor of CW-free survival. In univariate Cox hazard proportional analysis, CW was associated with the RA reservoir volume index (hazard ratio [HR] = 0.80). In multivariate analysis, CW was associated with World Health Organization functional class (HR = 4.3), RA minimum volume index (HR = 1.07), and RA reServoir volume index (HR = 0.73).
CONCLUSIONS: RA volume and reservoir function and their combined use with RVEF are novel predictors of CW in patients with pre-capillary PH. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved.

Effect of age difference of cerebral oxygen saturation to predict early outcome in pediatric cardiac surgery for ventricular septal defect.
Yasunori Yagi, Masataka Yamamoto, Hitoshi Saito, Toshihiro Mori, Yuji Morimoto, Takayoshi Oyasu, Tsuyoshi Tachibana, Yoichi M Ito
Circulation Control, 36, 2, 106, 110, Japan Society of Circulation Control in Medicine, 2015年, ［査読有り］
英語, 研究論文（学術雑誌）

Differential changes in quality of life components over 5 years in chronic obstructive pulmonary disease patients
Katsura Nagai, Hironi Makita, Masaru Suzuki, Kaoruko Shimizu, Satoshi Konno, Yoichi M. Ito, Masaharu Nishimura
INTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE, 10, 745, 757, DOVE MEDICAL PRESS LTD, 2015年, ［査読有り］
英語, 研究論文（学術雑誌）, Background: The aim of the study was to examine the longitudinal change in quality of life components of patients with chronic obstructive pulmonary disease (COPD).
Methods: In the Hokkaido COPD Cohort Study, 261 subjects were appropriately treated and followed over 5 years with a 74% follow-up rate at the end. The longitudinal changes in St George's Respiratory Questionnaire (SGRQ) scores were annually evaluated with forced expiratory volume in 1 second (FEV1). The subjects were classified into the rapid decliners, slow decliners, and sustainers based on Delta FEV1/year.
Results: The activity component of SGRQ generally deteriorated over time, and its annual decline was the greatest in the rapid decliners (<25th percentile). In contrast, the symptom component improved significantly year by year in the sustainers (>75 percentile), and it did not deteriorate even in the rapid decliners. Of the baseline data, predictors for worsening of the activity component were older age and lower body mass index. Larger reversibility was related to symptom component improvement. Of the follow-up data, Delta FEV1/year was the best predictor for worsening of the components of SGRQ. Continuous smoking was another factor for worsening of the activity component. For the symptom component, a history of exacerbation by admission definition was the determinant of its deterioration, whereas use of beta agonists was related to improvement.
Conclusion: The longitudinal changes of quality of life and their determinants are markedly different and independent between its components. The activity component of SGRQ generally deteriorated over years, while the symptom component rather improved in some patients with COPD under appropriate treatment.

呼吸不全に関する調査研究 酢酸PETによる肺高血圧症患者の右室エネルギー代謝に関する研究
西村正治, 吉永恵一郎, 大平洋, 辻野一三, 真鍋徳子, MIELNICZUK L, BEANLANDS R S B, 加藤千恵次, 葛西克彦, 真鍋治, 佐藤隆博, 藤井聡, 伊藤陽一, 富山勇輝, 玉木長良
呼吸不全に関する調査研究 平成26年度 総括・分担研究報告書, 257‐259, 2015年
日本語

Exploration of failure causes of an incomplete clinical trial in enrollment: A case study
Sakushima K, Horie N, Amano T, Mogi Y, Nishimura C, Shigematsu A, Oba K, Ito Y.M, Sato N
Japanese Pharmacology and Therapeutics, 43, s94, s98, 2015年, ［査読有り］

Time trend of injection drug errors before and after implementation of bar-code verification system
Ken Sakushima, Reona Umeki, Akira Endoh, Yoichi M. Ito, Yasuyuki Nasuhara
TECHNOLOGY AND HEALTH CARE, 23, 3, 267, 274, IOS PRESS, 2015年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Bar-code technology, used for verification of patients and their medication, could prevent medication errors in clinical practice.
OBJECTIVE: Retrospective analysis of electronically stored medical error reports was conducted in a university hospital.
METHODS: The number of reported medication errors of injected drugs, including wrong drug administration and administration to the wrong patient, was compared before and after implementation of the bar-code verification system for inpatient care.
RESULTS: A total of 2867 error reports associated with injection drugs were extracted. Wrong patient errors decreased significantly after implementation of the bar-code verification system (17.4/year vs. 4.5/year, p < 0.05), although wrong drug errors did not decrease sufficiently (24.2/year vs. 20.3/year). The source of medication errors due to wrong drugs was drug preparation in hospital wards.
CONCLUSION: Bar-code medication administration is effective for prevention of wrong patient errors. However, ordinary bar-code verification systems are limited in their ability to prevent incorrect drug preparation in hospital wards.

Effects and safety of ¹³¹I-metaiodobenzylguanidine (MIBG) radiotherapy in malignant neuroendocrine tumors: results from a multicenter observational registry.
Yoshinaga K, Oriuchi N, Wakabayashi H, Tomiyama Y, Jinguji M, Higuchi T, Kayano D, Fukuoka M, Inaki A, Toratani A, Okamoto S, Shiga T, Ito YM, Nakajo M, Nakajo M, Kinuya S, Drafting Committee, for Guidelines on Internal Radiotherapy with, I-MIBG, Japanese Society of Nuclear Medicine in, Oncology, Imunology, Japanese Society of, Nuclear Medicine
Endocrine journal, 61, 12, 1171, 1180, JAPAN ENDOCRINE SOC, 2014年12月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Effective treatments for malignant neuroendocrine tumors are under development. While iodine-131 metaiodobenzylguanidine (I-131-MIBG) radiotherapy has been used in the treatment of malignant neuroendocrine tumors, there are few studies evaluating its therapeutic effects and safety in a multicenter cohort. In the current study, we sought to evaluate the effects and safety of I-131-MIBG therapy for conditions including malignant pheochromocytoma and paraganglioma within a multicenter cohort. Forty-eight malignant neuroendocrine tumors (37 pheochromocytoma and 11 paraganglioma) from four centers underwent clinical I-131-MIBG radiotherapy. The tumor responses were observed before and 3 to 6 months after the I-131-MIBG radiotherapy in accordance with RECIST criteria. We also evaluated the data for any adverse effects. The four centers performed a total of 87 I-131-MIBG treatments on 48 patients between January 2000 and March 2009. Of the treatments, 65 were evaluable using RECIST criteria. One partial response (PR), 40 stable disease (SD), and 9 progressive disease (PD) in malignant pheochromocytoma were observed after each treatment. Fourteen SD and one PD-were observed in paraganglioma. Patients with normal hypertension (systolic blood pressure (BP) > 130 mmHg) showed significantly reduced systolic BP after the initial follow-up (n=10, 138.1 +/- 8.2 to 129.5 +/- 13.5 mmHg, P=0.03). In adult neuroendocrine tumors with a treatment-basis analysis, there were side effects following 41 treatments (47.1%) and most of them (90.2%) were minor. In this multicenter registry, PR or SD was achieved in 84.6% of the treatment occasions in adult neuroendocrine tumors through I-131-MIBG radiotherapy. This indicated that most of the I-131-MIBG radiotherapy was performed safely without significant side effects.

Current Practice in Japan for the Prevention and Treatment of Missing Data in Confirmatory Clinical Trials: A Survey of Japanese and Foreign Pharmaceutical Manufacturers
Shiro Tanaka, Satoru Fukinbara, Satoru Tsuchiya, Hideki Suganami, Yoichi M. Ito
THERAPEUTIC INNOVATION & REGULATORY SCIENCE, 48, 6, 717, 723, SAGE PUBLICATIONS INC, 2014年11月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, This study aims to survey the current practice in Japan for the prevention and treatment of missing data in clinical trials since the publication of regulatory guidelines on missing data issues. A web-based questionnaire was conducted among 65 member companies of the Japan Pharmaceutical Manufacturers Association in 2013. Responses were obtained on 187 clinical trials from 55 companies, including 42 based in Japan and 13 based in other countries. Missing data were most frequent in trials involving the central nervous system (65.2% had 10% missing data). Overall, last observation carried forward (LOCF) was the most popular method for handling missing data (45.0%), followed by mixed-effect models for repeated measures (15.5%), although this was used as frequently as LOCF imputation in central nervous system trials. Even after the publication of regulatory guidelines discouraging use of LOCF, LOCF imputation remains the most popular method for treating missing data among pharmaceutical manufacturers in Japan.

Prone-position acquisition of myocardial (123)I-metaiodobenzylguanidine (MIBG) SPECT reveals regional uptake similar to that found using (11)C-hydroxyephedrine PET/CT.
Keiichiro Yoshinaga, Yuuki Tomiyama, Osamu Manabe, Katsuhiko Kasai, Chietsugu Katoh, Kenichi Magota, Eriko Suzuki, Ken-Ichi Nishijima, Yuji Kuge, Yoichi M Ito, Nagara Tamaki
Annals of nuclear medicine, 28, 8, 761, 9, SPRINGER, 2014年10月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: (123)I-metaiodobenzylguanidine (MIBG) has been used to estimate cardiac sympathetic nervous innervation. Heterogeneous MIBG distribution is mainly associated with high physiological MIBG uptakes in the liver. We postulate that prone position acquisition might be especially effective for MIBG, providing for separation from high liver uptake similar to that provided by perfusion single-photon emission computed tomography (SPECT). We investigated whether prone-position acquisition improved MIBG image quality by comparing our results to those acquired using supine MIBG and high-quality (11)C-hydroxyephedrine (HED) positron emission tomography/computed tomography PET/CT. METHODS: Ten male volunteers (body mass index (BMI) 22.7 ± 3.4) underwent prone and supine MIBG and HED PET. Relative regional tracer uptake was estimated in early MIBG and HED. Acquired images were divided into 17 segments and were grouped into 4 regions: anterior, inferior, septum, and lateral. For each patient, the inferior/anterior ratio was calculated. RESULTS: The quality of images acquired using prone MIBG was better than that using supine MIBG (p < 0.05). Inferior and septum relative MIBG uptake was reduced in comparison with anterior or lateral MIBG uptake in the supine position (inferior vs. anterior: 69.0 ± 5.6 vs. 82.3 ± 4.6 %, p < 0.01; septum vs. lateral: 66.2 ± 5.1 vs. 81.9 ± 5.4 %, p < 0.01). Prone MIBG showed a significantly higher inferior/anterior uptake ratio in comparison with supine MIBG (n = 24, seg: 92.2 ± 7.2 vs. 83.6 ± 5.7 %, p < 0.05). However, intergroup differences in uptake ratio were demonstrated among prone and supine MIBG and HED. HED PET/CT still showed a higher uptake ratio in comparison with prone MIBG SPECT (103.9 ± 8.0 vs. 92.2 ± 7.2 %, p < 0.05). CONCLUSION: Even in normal male subjects, standard supine MIBG imaging showed reduced inferior and septum uptake. Uptake with prone MIBG imaging showed a significant improvement over that with supine imaging and was closer to uptake for HED PET/CT. This improvement may be the result of preventing intense uptake by the liver. Prone data acquisition may be a viable alternative in evaluating regional abnormalities using MIBG SPECT in men.

Simultaneous Analysis of the Gene Expression Profiles of Cancer and Stromal Cells in Endometrial Cancer
Yoko Iguchi, Yoichi M. Ito, Fumio Kataoka, Hiroyuki Nomura, Hideo Tanaka, Tatsuyuki Chiyoda, Shiho Hashimoto, Sadako Nishimura, Masashi Takano, Wataru Yamagami, Nobuyuki Susumu, Daisuke Aoki, Hiroshi Tsuda
GENES CHROMOSOMES & CANCER, 53, 9, 725, 737, WILEY-BLACKWELL, 2014年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, To address the role of cancer-stroma interactions, we performed gene expression profiling of both cancer and stroma, using matching samples of endometrial cancer (EC), and analyzed the relationship between the gene expression pattern and prognosis in EC. Sixty EC cases were included in this study (38 nonrecurrent and 22 recurrent). Cancer and stroma were separated by performing laser capture microdissection, and microarray analysis was performed separately on cancer and stromal cells. Genes related with progression-free survival (PFS) in cancer and stroma were analyzed using the Cox regression model, and we established a formula, based on the gene expression pattern of cancer and stroma, to predict recurrence using logistic regression. We estimated the accuracy of the formula using the 0.632 method. All cases were classified based on the 79 selected genes of cancer and stroma related to PFS, based on unsupervised clustering. A total of 143 genes in cancer, and 79 genes in stroma were significantly related with PFS. The estimated area under the curve of receiver operating characteristics curve in cancer and stroma to predict recurrence were 0.800 and 0.758, respectively. Based on the 79 genes of cancer, the 22 recurrent cases were divided into two groups, which generally correlated with the histological grade. In contrast, based on the 79 genes of stroma, the 22 recurrent cases displayed homogeneous gene expression, unrelated to the histological grade. We conclude that gene expression profiles of cancer and stroma can predict the recurrence of EC and stromal that gene expression does not depend on the cancer grade. (C) 2014 Wiley Periodicals, Inc.

Distinct Molecular Features of Different Macroscopic Subtypes of Colorectal Neoplasms
Kenichi Konda, Kazuo Konishi, Toshiko Yamochi, Yoichi M. Ito, Hisako Nozawa, Masayuki Tojo, Kensuke Shinmura, Mari Kogo, Atsushi Katagiri, Yutaro Kubota, Takashi Muramoto, Yuichiro Yano, Yoshiya Kobayashi, Toshihiro Kihara, Teppei Tagawa, Reiko Makino, Masafumi Takimoto, Michio Imawari, Hitoshi Yoshida
PLOS ONE, 9, 8, e103822, PUBLIC LIBRARY SCIENCE, 2014年08月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Colorectal adenoma develops into cancer with the accumulation of genetic and epigenetic changes. We studied the underlying molecular and clinicopathological features to better understand the heterogeneity of colorectal neoplasms (CRNs).
Methods: We evaluated both genetic (mutations of KRAS, BRAF, TP53, and PIK3CA, and microsatellite instability [MSI]) and epigenetic (methylation status of nine genes or sequences, including the CpG island methylator phenotype [CIMP] markers) alterations in 158 CRNs including 56 polypoid neoplasms (PNs), 25 granular type laterally spreading tumors (LST-Gs), 48 non-granular type LSTs (LST-NGs), 19 depressed neoplasms (DNs) and 10 small flat-elevated neoplasms (S-FNs) on the basis of macroscopic appearance.
Results: S-FNs showed few molecular changes except SFRP1 methylation. Significant differences in the frequency of KRAS mutations were observed among subtypes (68% for LST-Gs, 36% for PNs, 16% for DNs and 6% for LST-NGs) (P<0.001). By contrast, the frequency of TP53 mutation was higher in DNs than PNs or LST-Gs (32% vs. 5% or 0%, respectively) (P<0.007). We also observed significant differences in the frequency of CIMP between LST-Gs and LST-NGs or PNs (32% vs. 6% or 5%, respectively) (P<0.005). Moreover, the methylation level of LINE-1 was significantly lower in DNs or LST-Gs than in PNs (58.3% or 60.5% vs. 63.2%, P<0.05). PIK3CA mutations were detected only in LSTs. Finally, multivariate analyses showed that macroscopic morphologies were significantly associated with an increased risk of molecular changes (PN or LST-G for KRAS mutation, odds ratio [OR] 9.11; LST-NG or DN for TP53 mutation, OR 5.30; LST-G for PIK3CA mutation, OR 26.53; LST-G or DN for LINE-1 hypomethylation, OR 3.41).
Conclusion: We demonstrated that CRNs could be classified into five macroscopic subtypes according to clinicopathological and molecular differences, suggesting that different mechanisms are involved in the pathogenesis of colorectal tumorigenesis.

Attenuated right ventricular energetics evaluated using ¹¹C-acetate PET in patients with pulmonary hypertension.
Yoshinaga K, Ohira H, Tsujino I, Oyama-Manabe N, Mielniczuk L, Beanlands RS, Katoh C, Kasai K, Manabe O, Sato T, Fujii S, Ito YM, Tomiyama Y, Nishimura M, Tamaki N
European journal of nuclear medicine and molecular imaging, 41, 6, 1240, 50, SPRINGER, 2014年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: The right ventricle (RV) has a high capacity to adapt to pressure or volume overload before failing. However, the mechanisms of RV adaptation, in particular RV energetics, in patients with pulmonary hypertension (PH) are still not well understood. We aimed to evaluate RV energetics including RV oxidative metabolism, power and efficiency to adapt to increasing pressure overload in patients with PH using (11)C-acetate PET. METHODS: In this prospective study, 27 patients with WHO functional class II/III PH (mean pulmonary arterial pressure 39.8 ± 13.5 mmHg) and 9 healthy individuals underwent (11)C-acetate PET. (11)C-acetate PET was used to simultaneously measure oxidative metabolism (k mono) for the left ventricle (LV) and RV. LV and RV efficiency were also calculated. RESULTS: The RV ejection fraction in PH patients was lower than in controls (p = 0.0054). There was no statistically significant difference in LV k mono (p = 0.09). In contrast, PH patients showed higher RV k mono than did controls (0.050 ± 0.009 min(-1) vs. 0.030 ± 0.006 min(-1), p < 0.0001). PH patients exhibited significantly increased RV power (p < 0.001) and hence increased RV efficiency compared to controls (0.40 ± 0.14 vs. 0.017 ± 0.12 mmHg·mL·min/g, p = 0.001). CONCLUSION: The RV oxidative metabolic rate was increased in patients with PH. Patients with WHO functional class II/III PH also had increased RV power and efficiency. These findings may indicate a myocardial energetics adaptation response to increasing pulmonary arterial pressure.

デジタル/シミュレーターハイブリッドファントムの開発とUS-CT Fusion Imagingのバリデーション　　　　　　　　　　　　　　　
曽山 武士, 作原 祐介, 阿保 大介, Wang Jeff, 伊藤 陽一, 長谷川 悠, 工藤 與亮, 白土 博樹
IVR: Interventional Radiology, 29, Suppl., 200, 200, (一社)日本インターベンショナルラジオロジー学会, 2014年05月
日本語

Clinical features and determinants of COPD exacerbation in the Hokkaido COPD cohort study
Masaru Suzuki, Hironi Makita, Yoichi M. Ito, Katsura Nagai, Satoshi Konno, Masaharu Nishimura
EUROPEAN RESPIRATORY JOURNAL, 43, 5, 1289, 1297, EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2014年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Exacerbations are among the major factors that may affect the natural history of chronic obstructive pulmonary disease (COPD). The aim was to investigate the clinical characteristics and determinants of COPD exacerbations in our 5-year observational cohort study which had a very low exacerbation frequency.
A total of 279 patients with COPD participated in the Hokkaido COPD cohort study, and 268 subjects who had clinical data for multiple visits were analysed. Exacerbation was defined in multiple ways: the patient's subjective complaint, symptom definition, requiring prescription change, requiring antibiotic treatment, or requiring hospital admission.
Exacerbation frequency (events per person per year) was 0.78 +/- 1.16, 0.24 +/- 0.47, 0.20 +/- 0.43, 0.13 +/- 0.28 and 0.06 +/- 0.19 for subjective complaint and symptom, prescription, antibiotic and hospital admission definitions, respectively. Exacerbation events did not significantly affect the annual decline in forced expiratory volume in 1 s. A high St George's Respiratory Questionnaire total score, especially activity score, and a low body mass index were strongly associated with exacerbation-free survival, exacerbation frequency and development of recurrent exacerbations.
Despite the low exacerbation frequency in our cohort, impaired health-related quality of life and weight loss were found to be independent risk factors for COPD exacerbations.

The effects of a Gly16Arg ADRB2 polymorphism on responses to salmeterol or montelukast in Japanese patients with mild persistent asthma
Satoshi Konno, Nobuyuki Hizawa, Hironi Makita, Kaoruko Shimizu, Tohru Sakamoto, Fumio Kokubu, Takefumi Saito, Takeo Endo, Hiroki Ninomiya, Hiroaki Iijima, Norihiro Kaneko, Yoichi M. Ito, Masaharu Nishimura
PHARMACOGENETICS AND GENOMICS, 24, 5, 246, 255, LIPPINCOTT WILLIAMS & WILKINS, 2014年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background
Long-acting beta 2-agonists and leukotriene receptor antagonists are two principal agents that can be added to inhaled corticosteroids (ICS) for patients with asthma that is not adequately controlled by ICS alone. The Gly16Arg genotype of the beta 2-adrenergic receptor (ADRB2) gene may influence the bronchodilator effects of beta 2-agonists. We hypothesized that differential responses to long-acting beta 2-agonists or leukotriene receptor antagonists might be determined partly by the Gly16Arg polymorphism in Japanese asthma patients.
Materials and methods
This randomized, genotype-stratified, two-period crossover study included 80 patients with mild-to-moderate asthma (35 Arg/Arg and 45 Gly/Gly individuals). The primary study outcome was the difference in peak expiratory flow (Delta PEF) (Delta PEF, l/min) by genotype after 16 weeks of treatment with salmeterol (Delta PEFsal) or montelukast (Delta PEFmon). In addition, multivariate analyses were used to identify independent factors that were predictive of responses to each treatment.
Results
The mean Delta PEFsal-Delta PEFmon was 19.3 +/- 46.6 among Arg/Arg individuals and 16.8 +/- 51.5 among Gly/Gly individuals, indicating that the Gly16Arg genotype did not influence the differential bronchodilator effect of the two agents. Multivariate analysis showed that higher peripheral eosinophil counts were associated with better response to salmeterol (P < 0.05).
Conclusion
The Gly16Arg genotype did not influence the differential bronchodilator effect of salmeterol or montelukast as an add-on therapy to ICS within 16 weeks of follow-up. Higher peripheral eosinophil counts may be associated with better responses to salmeterol in combination with ICS.

Prognostic Factors for Survival in Patients with High-Grade Meningioma and Recurrence-Risk Stratification for Application of Radiotherapy
Shigeru Yamaguchi, Shunsuke Terasaka, Hiroyuki Kobayashi, Katsuyuki Asaoka, Hiroaki Motegi, Hiroshi Nishihara, Hiromi Kanno, Rikiya Onimaru, Yoichi M. Ito, Hiroki Shirato, Kiyohiro Houkin
PLOS ONE, 9, 5, e97108, PUBLIC LIBRARY SCIENCE, 2014年05月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Radiotherapy for high-grade meningioma (HGM) is one of the essential treatment options for disease control. However, appropriate irradiation timing remains under debate. The object of this study is to discern which prognostic factors impact recurrence in HGM patients and to propose a risk-stratification system for the application of postoperative radiotherapy.Methods: We retrospectively reviewed 55 adult patients who were diagnosed with Grade II and III intracranial meningioma. Cox regression models were applied to the analysis for impact on early recurrence in HGM patients without postoperative radiotherapy.Results: Grade III malignancy (P = 0.0073) and transformed histology (P = 0.047) proved to be significantly poor prognostic factors of early recurrence by multivariate analysis. The other candidates for recurrence factors were Simpson Grade 3-5 resection, preoperative Karnofsky Performance status, <= 70%, and MIB-1 labeling index >= 15%. According to these prognostic factors, postoperative HGM patients could be stratified into three recurrence-risk groups. The prognoses were significantly different between each group, as the 3-year actual recurrence-free rates were 90% in low-risk group, 31% in intermediate-risk group, and 15% in high-risk group.Conclusion: We propose recurrence-risk stratification for postoperative HGM patients using clinically available factors. Our results suggest that the prognosis for patients with high-risk HGMs is dismal, whereas HGM patients belonging to the low-risk group could have favorable prognoses. This stratification provides us with the criteria necessary to determine whether to apply adjuvant radiotherapy to postoperative HGM patients, and to also help identify potentially curable HGMs without adjuvant radiotherapy.

Prospective phase II study of image-guided local boost using a real-time tumor-tracking radiotherapy (RTRT) system for locally advanced bladder cancer
Nishioka K, Shimizu S, Shinohara N, Ito Y. M, Abe T, Maruyama S, Kinoshita R, Harada K, Nishikawa N, Miyamoto N, Onimaru R, Shirato H
Jpn J Clin Oncol, 44, 1, 28, 35, 2014年, ［査読有り］

Prospective Phase II Study of Image-guided Local Boost Using a Real-time Tumor-tracking Radiotherapy (RTRT) System for Locally Advanced Bladder Cancer
Kentaro Nishioka, Shinichi Shimizu, Nobuo Shinohara, Yoichi M. Ito, Takashige Abe, Satoru Maruyama, Rumiko Kinoshita, Keiichi Harada, Noboru Nishikawa, Naoki Miyamoto, Rikiya Onimaru, Hiroki Shirato
JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 44, 1, 28, 35, OXFORD UNIV PRESS, 2014年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The real-time tumor-tracking radiotherapy system with fiducial markers has the advantage that it can be used to verify the localization of the markers during radiation delivery in real-time. We conducted a prospective Phase II study of image-guided local-boost radiotherapy for locally advanced bladder cancer using a real-time tumor-tracking radiotherapy system for positioning, and here we report the results regarding the safety and efficacy of the technique.
Twenty patients with a T2-T4N0M0 urothelial carcinoma of the bladder who were clinically inoperable or refused surgery were enrolled. Transurethral tumor resection and 40 Gy irradiation to the whole bladder was followed by the transurethral endoscopic implantation of gold markers in the bladder wall around the primary tumor. A boost of 25 Gy in 10 fractions was made to the primary tumor while maintaining the displacement from the planned position at less than 2 mm during radiation delivery using a real-time tumor-tracking radiotherapy system. The toxicity, local control and survival were evaluated.
Among the 20 patients, 14 were treated with concurrent chemoradiotherapy. The median follow-up period was 55.5 months. Urethral and bowel late toxicity (Grade 3) were each observed in one patient. The local-control rate, overall survival and cause-specific survival with the native bladder after 5 years were 64, 61 and 65.
Image-guided local-boost radiotherapy using a real-time tumor-tracking radiotherapy system can be safely accomplished, and the clinical outcome is encouraging. A larger prospective multi-institutional study is warranted for more precise evaluations of the technological efficacy and patients quality of life.

Simple prediction of right ventricular ejection fraction using tricuspid annular plane systolic excursion in pulmonary hypertension
Takahiro Sato, Ichizo Tsujino, Noriko Oyama-Manabe, Hiroshi Ohira, Yoichi M. Ito, Hiroyuki Sugimori, Asuka Yamada, Chisa Takashina, Taku Watanabe, Masaharu Nishimura
INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING, 29, 8, 1799, 1805, SPRINGER, 2013年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The present study examined whether tricuspid annular plane systolic excursion (TAPSE) can simply predict right ventricular ejection fraction (RVEF) in patients with pulmonary hypertension (PH). The TAPSE cut-off value to predict reduced RVEF was also evaluated. The association between TAPSE and cardiac magnetic resonance imaging (CMRI)-derived RVEF was examined in 53 PH patients. The accuracy of the prediction equation to calculate RVEF using TAPSE was also evaluated. In PH patients, TAPSE was strongly correlated with CMRI-derived RVEF in PH patients (r = 0.86, p < 0.0001). We then examined the accuracy of the two equations: the original regression equation (RVEF = 2.01 x TAPSE + 0.6) and the simplified prediction equation (RVEF = 2 x TAPSE). Bland-Altman plot showed that the mean difference +/- A limits of agreement was 0.0 +/- A 10.6 for the original equation and -0.6 +/- A 10.6 for the simplified equation. Intraclass correlation coefficient was 0.84 for the original and 0.82 for the simplified equation. Normal RVEF was considered to be a parts per thousand yen40 % based on the data from 53 matched controls, and the best TAPSE cut-off value to determine reduced RVEF (< 40 %) was calculated to be 19.7 mm (sensitivity 88.9 %, specificity 84.6 %). A simple equation of RVEF = 2 x TAPSE enables easy prediction of RVEF using TAPSE, an easily measurable M-mode index of echocardiography. TAPSE of 19.7 mm predicts reduced RVEF in PH patients with clinically acceptable sensitivity and specificity.

Dose-volume analysis for respiratory toxicity in intrathoracic esophagealcancer patients treated with definitive chemoradiotherapy using extended fields
Satoshi Tanabe, Miyako Myojin, Shinichi Shimizu, Masaharu Fujino, Hiroaki Takahashi, Hiroki Shirato, Yoichi M. Ito, Masayori Ishikawa, Masao Hosokawa
Journal of Radiation Research, 54, 6, 1085, 1094, OXFORD UNIV PRESS, 2013年11月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Purpose: We evaluated the relationship between dosimetric parameters (DPs) and the incidence of radiation pneumonitis (RP) and investigated the feasibility of a proposed treatment planning technique with the potential of reducing RP in esophageal cancer patients treated with definitive chemoradiotherapy using extended fields. Patients and Methods: A total of 149 patients with locally advanced esophageal cancer were prospectively enrolled for extended-field radiotherapy (EFRT) to three-field regional lymphatics between September 2004 and June 2009. We retrospectively reviewed 86 consecutive patients who were treated with a total dose of 50.4 Gy ( plus an optional 9 Gy boost) and were available for dose-volume analysis. Lung DPs of patients in the Grade 0 1 RP (RPG≤1) group and the Grade 2 5 RP (RPG≥2) group were compared. We compared the proposed plan with the conventional plan to 50.4 Gy on DPs for each case. Results: Of these 86 patients, 10 (12%) developed RPG≥2 (Grade 2, n = 2 patients
Grade 3, n = 3
Grade 4, n = 3
Grade 5, n = 2). The patients in the RPG≤1 group showed significantly lower (P <
0.05) V5 and V10 values for the whole lung compared with those in the RPG≥2 group. There were two advantages gained from the proposed plan for V5 (<
55%) and V10 (<
37%) values and the conformity of the PTV. Conclusion: The increase in the volume of the lung exposed to low doses of EFRT was found to be associated with the incidence of RP. Our proposed plan is likely to reduce the incidence of RP. © The Author 2013. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Therapeutic Radiology and Oncology.

Clinical utility of high-throughput glycome analysis in patients with pancreatic cancer
Kazuhiro Nouso, Maho Amano, Yoichi M. Ito, Koji Miyahara, Yuki Morimoto, Hironari Kato, Koichiro Tsutsumi, Takeshi Tomoda, Naoki Yamamoto, Shinichiro Nakamura, Sayo Kobayashi, Kenji Kuwaki, Hiroaki Hagihara, Hideki Onishi, Yasuhiro Miyake, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Taku Nakahara, Shin-Ichiro Nishimura, Kazuhide Yamamoto
JOURNAL OF GASTROENTEROLOGY, 48, 10, 1171, 1179, SPRINGER JAPAN KK, 2013年10月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Most of the glycan changes reported in cancers were based on the examinations of a small number of patients or particular proteins. The aim of this study was to determine the changes of the serum N-glycan profile comprehensively in a large number of pancreatic cancer patients and investigate its clinical utility.
Glycan levels in the serum of 92 pancreatic cancer patients and 243 healthy volunteers (HLT) were examined by comprehensive quantitative high-throughput glycome analysis and were compared with clinical parameters.
Out of 66 glycans detected, 15 were differentially expressed in pancreatic cancer, and 10 out of the 15 glycans were significantly up-regulated in cases with distant metastasis. There was a clear increase in overall expression of serum glycans, especially highly-branched glycans with fucose moieties, in pancreatic cancer. Among these 15 glycans, a tri-antennary complex type glycan (m/z 3195) showed the highest area under the receiver operating characteristic curve (AUROC = 0.799) for the diagnosis of pancreatic cancer. The ratio of pairs of glycans on the same path of the biosynthesis pathway (m/z 3195/1914) was found to be significantly higher in pancreatic cancer than in HLT (median = 1.11 and 0.41, respectively; p < 0.0001, AUROC = 0.831). For this pair ratio, the hazard ratio for survival (2.60, 95 % CI = 1.44-4.79) was higher than that of any single glycan and 1-year survival of patients with a high and low ratio was 36.9 and 69.2 %, respectively, (p = 0.001).
Comprehensive glycome analysis can be used to know the presence of pancreatic cancer, distant metastasis, and patient prognosis, simultaneously.

Elevated (18)F-fluorodeoxyglucose uptake in the interventricular septum is associated with atrioventricular block in patients with suspected cardiac involvement sarcoidosis.
Osamu Manabe, Hiroshi Ohira, Keiichiro Yoshinaga, Takahiro Sato, Alisa Klaipetch, Noriko Oyama-Manabe, Yoichi M Ito, Ichizo Tsujino, Masaharu Nishimura, Nagara Tamaki
European journal of nuclear medicine and molecular imaging, 40, 10, 1558, 66, SPRINGER, 2013年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: Cardiac involvement in sarcoidosis is one of the leading causes of death associated with abnormalities of the conduction system. (18)F-FDG PET is useful for detecting inflammatory lesions in cardiac sarcoidosis. However, the relationship between ECG abnormalities and focal (18)F-FDG uptake has not been studied. The aim of this study was to evaluate the relationship between electrocardiogram (ECG) abnormalities and the location of elevated myocardial (18)F-FDG uptake in patients with sarcoidosis. METHODS: Included in the study were 50 patients (56.3 ± 14.9 years old) with histologically proven sarcoidosis with suspected cardiac involvement based on ECG or echocardiography. All patients had fasted for at least 6 h and were given unfractionated heparin (50 IU/kg) intravenously to reduce the physiological (18)F-FDG uptake in the myocardium. The left ventricle (LV) wall was divided into 17 segments by visual analysis. Obvious accumulation in each segment was defined as positive. RESULTS: Of the 50 patients, 33 showed some ECG abnormalities, including atrioventricular (AV) block in 13. Patients with abnormal ECG findings had a higher number of regions with (18)F-FDG uptake than patients without ECG abnormality (3.48 ± 2.73 vs. 1.41 ± 2.09 regions, p = 0.0051). Among ECG abnormalities, the predictor for interventricular septum wall (18)F-FDG involvement was AV block (p = 0.0025). CONCLUSION: Patients with ECG abnormalities showed a higher number of abnormal (18)F-FDG myocardial uptake regions than patients without ECG abnormalities. In particular, focal (18)F-FDG uptake in the interventricular septum in cardiac sarcoidosis was associated with AV block. Therefore, determination of regional (18)F-FDG distribution might contribute to patient management in cardiac sarcoidosis.

Temporal trends of perfluoroalkyl acids in plasma samples of pregnant women in Hokkaido, Japan, 2003-2011
Emiko Okada, Ikuko Kashino, Hideyuki Matsuura, Seiko Sasaki, Chihiro Miyashita, Jun Yamamoto, Tamiko Ikeno, Yoichi M. Ito, Toru Matsumura, Akiko Tamakoshi, Reiko Kishi
ENVIRONMENT INTERNATIONAL, 60, 89, 96, PERGAMON-ELSEVIER SCIENCE LTD, 2013年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Perfluoroalkyl acids (PFAAs) are persistent organic pollutants that are used in a wide range of consumer products. Recent epidemiological studies have shown that prenatal exposure to toxic levels of PFAAs in the environment may adversely affect fetal growth and humoral immune response in infants and children. Here we have characterized levels of prenatal exposure to PFAA between 2003 and 2011 in Hokkaido, Japan, by measuring PFAA concentrations in plasma samples from pregnant women. The study population comprised 150 women who enrolled in a prospective birth cohort study conducted in Hokkaido. Eleven PFAAs were measured in maternal plasma samples using simultaneous analysis by ultra-performance liquid chromatography coupled to triple quadrupole tandem mass spectrometry. At the end of the study, in 2011, age- and parity-adjusted mean concentrations of perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluorotridecanoic acid (PFTrDA), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) were 1.35 ng/mL, 1.26 ng/mL, 0.66 ng/mL, 1.29 ng/mL, 025 ng/ml, 0.33 ng/mL, 028 ng/mL, and 3.86 ng/mL, respectively. Whereas PFOS and PFOA concentrations declined 8.4%/y and 3.1%/y, respectively, PFNA and PFDA levels increased 4.7%/y and 2.4%/y, respectively, between 2003 and 2011. PFUnDA, PFDoDA, and PFTrDA were detected in the vast majority of maternal samples, but no significant temporal trend was apparent. Future studies must involve a larger population of pregnant women and their children to determine the effects of prenatal exposure to PFAA on health outcomes in infants and children. (C) 2013 Elsevier Ltd. All rights reserved.

Co-Overexpression of GEP100 and AMAP1 Proteins Correlates with Rapid Local Recurrence after Breast Conservative Therapy
Rumiko Kinoshita, Jin-Min Nam, Yoichi M. Ito, Kanako C. Hatanaka, Ari Hashimoto, Haruka Handa, Yutaro Otsuka, Shigeru Hashimoto, Yasuhito Onodera, Mitsuchika Hosoda, Shunsuke Onodera, Shinichi Shimizu, Shinya Tanaka, Hiroki Shirato, Mishie Tanino, Hisataka Sabe
PLOS ONE, 8, 10, e76791, PUBLIC LIBRARY SCIENCE, 2013年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, A major problem of current cancer research and therapy is prediction of tumor recurrence after initial treatment, rather than the simple biological characterization of the malignancy and proliferative properties of tumors. Breast conservation therapy (BCT) is a well-approved, standard treatment for patients with early stages of breast cancer, which consists of lumpectomy and whole-breast irradiation. In spite of extensive studies, only 'age' and 'Ki-67 positivity' have been identified to be well correlated with local recurrence after BCT. An Arf6 pathway, activated by GEP100 under receptor tyrosine kinases (RTKs) and employs AMAP1 as its effector, is crucial for invasion and metastasis of some breast cancer cells. This pathway activates beta 1 integrins and perturbs E-cadherin-based adhesions, hence appears to be integral for epithelial-mesenchymal transdifferentiation (EMT). We here show that expression of the Arf6 pathway components statistically correlates with rapid local recurrence after BCT. We retrospectively analyzed four hundred seventy-nine patients who received BCT in Hokkaido University Hospital, and found 20 patients had local recurrence. We then analyzed pathological samples of patients who experienced local recurrence by use of Kaplan-Meier analysis, Stepwise regression analysis and the t-test, coupled with immunostaining, and found that co-overexpression of GEP100 and AMAP1 correlates with rapidity of the local recurrence. Their margin-status, node-positivity, and estrogen receptor (ER)-or progesterone receptor (PgR)positivity did not correlated with the rapidity. This study is the first to show that expression of a certain set of proteins correlates with the rapidity of local recurrence. Our results are useful not only for prediction, but highlight the possibility of developing novel strategies to block local recurrence. We also discuss why mRNAs encoding these proteins have not been identified to correlate with local recurrence by previous conventional gene expression profiling analyses.

Right atrial volume and phasic function in pulmonary hypertension
Takahiro Sato, Ichizo Tsujino, Noriko Oyama-Manabe, Hiroshi Ohira, Yoichi M. Ito, Asuka Yamada, Daisuke Ikeda, Taku Watanabe, Masaharu Nishimura
INTERNATIONAL JOURNAL OF CARDIOLOGY, 168, 1, 420, 426, ELSEVIER IRELAND LTD, 2013年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Few studies have focused on right atrial (RA) structure and function in pulmonary hypertension (PH). We sought to evaluate RA volume and phasic function using cardiac magnetic resonance (CMR), and to examine their clinical relevance in PH.
Methods: We prospectively studied 50 PH patients and 21 control subjects. RA volume and indices of phasic function (reservoir volume, ejection fraction [EF], and conduit volume) were evaluated by CMR.
Results: Maximum RA volume index was significantly higher in PH patients (56 [44-70] ml/m(2)) than in controls (40 [30-48] ml/m(2)) (p<0.001). Reservoir volume index was significantly lower in PH than in controls (p<0.001), but conduit volume index was higher in PH than in controls (p=0.008). RA EF was similar when comparing the two groups (p=0.925). Interestingly, RA EF was increased in PH patients with WHO functional class III patients as compared with controls (p<0.001) but was reduced in advanced PH patients with WHO functional class IV (p<0.01). Maximum RA volume and RA EF significantly correlated with pulmonary hemodynamic indices, atrial and brain natriuretic hormone levels, and CMR-derived right ventricular indices. By contrast, RA reservoir volume correlated with cardiac index and 6-minute walk distance.
Conclusions: PH is associated with increased size, decreased reservoir function, and increased conduit function of the right atrium. RA systolic function indicated by RA EF increases in patients with mild to moderate PH but decreases in patients with advanced PH. Varying associations between RA indices and conventional PH indices suggest their unique role in the management of PH. (c) 2012 Elsevier Ireland Ltd. All rights reserved.

Imaging characteristics of cardiac dominant diffuse large B-cell lymphoma demonstrated with MDCT and PET/CT.
Yasuka Kikuchi, Noriko Oyama-Manabe, Osamu Manabe, Masanao Naya, Yoichi M Ito, Kanako C Hatanaka, Hiroyuki Tsutsui, Satoshi Terae, Nagara Tamaki, Hiroki Shirato
European journal of nuclear medicine and molecular imaging, 40, 9, 1337, 44, SPRINGER, 2013年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, PURPOSE: To investigate the specific imaging findings of multidetector row CT (MDCT) and PET/CT with(18)F-FDG in cardiac dominant diffuse large B-cell lymphoma (DLBCL) in comparison with other cardiac tumours. METHODS: Five patients with DLBCL and 12 patients with other cardiac tumours including pericardial tumours were retrospectively reviewed. Among the patients with other cardiac tumours, seven had metastatic tumours, three had benign tumours, and two had other malignant cardiac tumours. The location of the cardiac mass, the encasement of the coronary artery surrounded by the mass, and pericardial effusion were evaluated using MDCT. The disease activity of the cardiac tumour was also evaluated by PET/CT. RESULTS: Four of the five DLBCL patients had primarily right-sided cardiac lesions, which was seen significantly more frequently in DLBCL than in other cardiac tumours (p = 0.028). All cardiac DLBCL lesions were located around the atrioventricular groove and encased the coronary arteries. ECG-gated cardiac MDCT showed that there was no apparent stenosis of the coronary arteries. Large amounts of pericardial effusion were seen in all DLBCL patients. PET/CT revealed significantly higher FDG uptake in DLBCL than in other cardiac malignant tumours, with no overlap (p = 0.0007). CONCLUSION: The combination of a right-sided cardiac mass with a large pericardial effusion and no apparent stenosis of the encased coronary artery revealed by MDCT and a high maximum standard uptake value were the specific findings in cardiac dominant DLBCL.

Impaired integrity of the brain parenchyma in non-geriatric patients with major depressive disorder revealed by diffusion tensor imaging.
Khin K Tha, Satoshi Terae, Shin Nakagawa, Takeshi Inoue, Nobuki Kitagawa, Yuki Kako, Yasuya Nakato, Kawser Akter Popy, Noriyuki Fujima, Yuri Zaitsu, Daisuke Yoshida, Yoichi M Ito, Tamaki Miyamoto, Tsukasa Koyama, Hiroki Shirato
Psychiatry research, 212, 3, 208, 15, 2013年06月30日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Diffusion tensor imaging (DTI) is considered to be able to non-invasively quantify white matter integrity. This study aimed to use DTI to evaluate white matter integrity in non-geriatric patients with major depressive disorder (MDD) who were free of antidepressant medication. DTI was performed on 19 non-geriatric patients with MDD, free of antidepressant medication, and 19 age-matched healthy subjects. Voxel-based and histogram analyses were used to compare fractional anisotropy (FA) and mean diffusivity (MD) values between the two groups, using two-sample t tests. The abnormal DTI indices, if any, were tested for correlation with disease duration and severity, using Pearson product-moment correlation analysis. Voxel-based analysis showed clusters with FA decrease at the bilateral frontal white matter, anterior limbs of internal capsule, cerebellum, left putamen and right thalamus of the patients. Histogram analysis revealed lower peak position of FA histograms in the patients. FA values of the abnormal clusters and peak positions of FA histograms of the patients exhibited moderate correlation with disease duration and severity. These results suggest the implication of frontal-subcortical circuits and cerebellum in MDD, and the potential utility of FA in evaluation of brain parenchymal integrity.

Impaired integrity of the brain parenchyma in non-geriatric patients with major depressive disorder revealed by diffusion tensor imaging
Khin K. Tha, Satoshi Terae, Shin Nakagawa, Takeshi Inoue, Nobuki Kitagawa, Yuki Kako, Yasuya Nakato, Kawser Akter Popy, Noriyuki Fujima, Yuri Zaitsu, Daisuke Yoshida, Yoichi M. Ito, Tamaki Miyamoto, Tsukasa Koyama, Hiroki Shirato
PSYCHIATRY RESEARCH-NEUROIMAGING, 212, 3, 208, 215, ELSEVIER IRELAND LTD, 2013年06月, ［査読有り］
英語, 研究論文（学術雑誌）, Diffusion tensor imaging (DTI) is considered to be able to non-invasively quantify white matter integrity. This study aimed to use DTI to evaluate white matter integrity in non-geriatric patients with major depressive disorder (MDD) who were free of antidepressant medication. DTI was performed on 19 non-geriatric patients with MDD, free of antidepressant medication, and 19 age-matched healthy subjects. Voxel-based and histogram analyses were used to compare fractional anisotropy (FA) and mean diffusivity (MD) values between the two groups, using two-sample t tests. The abnormal DTI indices, if any, were tested for correlation with disease duration and severity, using Pearson product-moment correlation analysis. Voxel-based analysis showed clusters with FA decrease at the bilateral frontal white matter, anterior limbs of internal capsule, cerebellum, left putamen and right thalamus of the patients. Histogram analysis revealed lower peak position of FA histograms in the patients. FA values of the abnormal clusters and peak positions of FA histograms of the patients exhibited moderate correlation with disease duration and severity. These results suggest the implication of frontal-subcortical circuits and cerebellum in MDD, and the potential utility of FA in evaluation of brain parenchymal integrity. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

Paradoxical Interventricular Septal Motion as a Major Determinant of Late Gadolinium Enhancement in Ventricular Insertion Points in Pulmonary Hypertension
Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Noriko Oyama-Manabe, Yoichi M. Ito, Teruo Noguchi, Asuka Yamada, Daisuke Ikeda, Taku Watanabe, Masaharu Nishimura
PLOS ONE, 8, 6, e66724, PUBLIC LIBRARY SCIENCE, 2013年06月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: This study investigated the major clinical determinants of late gadolinium enhancement (LGE) at ventricular insertion points (VIPs) commonly seen in patients with pulmonary hypertension (PH).
Methods: Forty-six consecutive PH patients (mean pulmonary artery pressure >= 25 mmHg at rest) and 21 matched controls were examined. Right ventricular (RV) morphology, function and LGE mass volume at VIPs were assessed by cardiac magnetic resonance (CMR). Radial motion of the left ventricular (LV) wall and interventricular septum (IVS) was assessed by speckle-tracking echocardiography. Paradoxical IVS motion index was then calculated. Univariate and multivariate regression analysis were conducted to characterize the relationship between LGE volume at VIPs and PH-related clinical indices, including the paradoxical IVS motion index.
Results: Mean pulmonary arterial pressure (MPAP) of PH patients was 3869 mmHg. LGE at VIPs was observed in 42 of 46 PH patients, and the LGE volume was 2.02 mL (0.47-2.99 mL). Significant correlations with LGE volume at VIPs were observed for MPAP (r = 0.50) and CMR-derived parameters [RV mass index (r = 0.53), RV end-diastolic volume index (r = 0.53), RV ejection fraction (r = -0.56), and paradoxical IVS motion index (r = 0.77)]. In multiple regression analysis, paradoxical IVS motion index alone significantly predicted LGE volume at VIPs (p<0.001).
Conclusions: LGE at VIPs seen in patients with PH appears to reflect altered IVS motion rather than elevated RV pressure or remodeling. Long-term studies would be of benefit to characterize the clinical relevance of LGE at VIPs.

7対1看護導入がインシデント報告件数に与えた影響について 新人看護職数の増加に着目して
南須原 康行, 佐久嶋 研, 奥原 芳子, 渋谷 かをり, 伊藤 陽一, 石川 誠, 宝金 清博
日本医療マネジメント学会雑誌, 14, 1, 25, 30, (NPO)日本医療マネジメント学会, 2013年05月
日本語, 北海道大学病院における2003年度から2009年度までの7年間にわたるインシデントレポートの中から、看護職によって報告されたものを抽出し、報告者の経験年数、レポート件数、場面などについて分析を行った。7年間で看護職から報告されたインシデントレポート総数は12,798件であった。7対1看護の導入により2007年度に145名の看護職の増員があり、総看護職の増員が22.0%であったのに対し、インシデントレポート件数は33.0%の増加であった。2007年度は総看護職数における1年目看護職数の割合が高く、1年目看護職による報告件数の占める割合が他の年度と比較して高かった。一方、1年目看護職1人あたりの平均年間報告件数の経年変化をみると、2007年度はそれ以前に比べて増加していなかった。看護職の増員は、看護職1人あたりのインシデントレポート件数の減少には繋がらなかった。看護職1年目ではインシデント全体に占める処方・与薬の割合が、2・3年目、4年目以上と比較して有意に大きかった。その内訳では、末梢静脈点滴なかでも投与速度に関するものの割合が、1年目および2・3年目は4年目以上に比べて有意に大きかった。看護職の新人教育においては、新人が関与する可能性の高いインシデントに重点をおいた教育が必要であろう。(著者抄録)

High Reproducibility of Tumor Hypoxia Evaluated by F-18-Fluoromisonidazole PET for Head and Neck Cancer
Shozo Okamoto, Tohru Shiga, Koichi Yasuda, Yoichi M. Ito, Keiichi Magota, Katsuhiko Kasai, Yuji Kuge, Hiroki Shirato, Nagara Tamaki
JOURNAL OF NUCLEAR MEDICINE, 54, 2, 201, 207, SOC NUCLEAR MEDICINE INC, 2013年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Tumor hypoxia is well known to be radiation resistant. F-18-fluoromisonidazole (F-18-FMISO) PET has been used for noninvasive evaluation of hypoxia. Quantitative evaluation of F-18-FMISO uptake is thus expected to play an important role in the planning of dose escalation radiotherapy. However, the reproducibility of F-18-FMISO uptake has remained unclarified. We therefore investigated the reproducibility of tumor hypoxia by using quantitative analysis of F-18-FMISO uptake. Methods: Eleven patients with untreated head and neck cancer underwent 2 F-18-FMISO PET/CT scans (F-18-FMISO1 and F-18-FMISO2) with a 48-h interval prospectively. All images were acquired at 4 h after F-18-FMISO injection for 10 min. The maximum standardized uptake (SUVmax), tumor-to-blood ratio (TBR), and tumor-to-muscle ratio (TMR) of F-18-FMISO uptake were statistically compared between the 2 F-18-FMISO scans by use of intraclass correlation coefficients (ICCs). The hypoxic volume was calculated as the area with a TBR of greater than or equal to 1.5 or the area with a TMR of greater than or equal to 1.25 to assess differences in hypoxic volume between the 2 F-18-FMISO scans. The distances from the maximum uptake locations of the F-18-FMISO1 images to those of the F-18-FMISO2 images were measured to evaluate the locations of F-18-FMISO uptake. Results: The SUVmax (mean +/- SD) for F-18-FMISO1 and F-18-FMISO2 was 3.16 +/- 1.29 and 3.02 +/- 1.12, respectively, with the difference between the 2 scans being 7.0% +/- 4.6%. The TBRs for F-18-FMISO1 and F-18-FMISO2 were 2.98 +/- 0.83 and 2.97 +/- 0.64, respectively, with a difference of 9.9% +/- 3.3%. The TMRs for F-18-FMISO1 and F-18-FMISO2 were 2.25 +/- 0.71 and 2.19 +/- 0.67, respectively, with a difference of 7.1% +/- 5.3%. The ICCs for SUVmax, TBR, and TMR were 0.959, 0.913, and 0.965, respectively. The difference in hypoxic volume based on TBR was 1.8 +/- 1.8 mL, and the difference in hypoxic volume based on TMR was 0.9 +/- 1.3 mL, with ICCs of 0.986 and 0.996, respectively. The maximum uptake locations of the F-18-FMISO1 images were different from those of the F-18-FMISO2 images and were within the full width at half maximum of the PET/CT scanner, except in 1 case. Conclusion: The values for F-18-FMISO PET uptake and hypoxic volume in head and neck tumors between the 2 F-18-FMISO scans were highly reproducible. Such high reproducibility of tumor hypoxia is promising for accurate radiation planning.

自主臨床研究における予定症例登録数未達の原因に関する関係者へのインタビュー調査　　　　　　　　　　　　　　　
堀江 奈穂, 佐久嶋 研, 大庭 幸治, 西本 尚樹, 伊藤 陽一, 佐藤 典宏
臨床薬理, 43, Suppl., S265, S265, (一社)日本臨床薬理学会, 2012年10月
日本語

転倒・転落防止及び対応に関する看護師の意識調査　　　　　　　　　　　　　　　
南須原 康行, 佐久嶋 研, 奥原 芳子, 渋谷 かをり, 石川 誠, 伊藤 陽一, 宝金 清博
医療の質・安全学会誌, 7, Suppl., 205, 205, (一社)医療の質・安全学会, 2012年10月
日本語

リストバンド照合による注射製剤における患者間違いインシデントの減少とコスト
佐久嶋 研, 南須原 康行, 奥原 芳子, 渋谷 かをり, 伊藤 陽一, 梅木 玲緒奈, 遠藤 晃, 宝金 清博
日本医療マネジメント学会雑誌, 13, Suppl., 389, 389, (NPO)日本医療マネジメント学会, 2012年09月
日本語

Clinical characteristics and determinants of exacerbation in Japanese patients with COPD: Hokkaido COPD cohort study results
Masaru Suzuki, Hironi Makita, Satoshi Konno, Kaoruko Shimizu, Natsuko Taniguchi, Yoichi M. Ito, Masaharu Nishimura
EUROPEAN RESPIRATORY JOURNAL, 40, EUROPEAN RESPIRATORY SOC JOURNALS LTD, 2012年09月
英語

Hyperintense putaminal rim at 1.5 T: prevalence in normal subjects and distinguishing features from multiple system atrophy.
Khin K Tha, Satoshi Terae, Akiko Tsukahara, Hiroyuki Soma, Ryo Morita, Ichiro Yabe, Yoichi M Ito, Hidenao Sasaki, Hiroki Shirato
BMC neurology, 12, 39, 39, BIOMED CENTRAL LTD, 2012年06月18日, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Hyperintense putaminal rim (HPR) is an important magnetic resonance imaging (MRI) sign for multiple system atrophy (MSA). Recent studies have suggested that it can also be observed in normal subjects at 3 T. Whether it can be observed in normal subjects at 1.5 T is not known. This study aimed to determine whether HPR could be observed in normal subjects at 1.5 T; and if so, to establish its prevalence, the MRI characteristics, and the features which distinguish from HPR in MSA patients. METHODS: Axial T2-weighted images of 130 normal subjects were evaluated for the prevalence of HPR, its age and gender distribution, laterality, maximum dimension, association with hypointensity of nearby putamen, and presence of discontinuity. To distinguish from that observed in MSA, axial T2-weighted images of 6 MSA patients with predominant parkinsonism (MSA-P) and 15 MSA patients with predominant cerebellar symptoms (MSA-C) were also evaluated. The characteristics of HPR were compared between these patients and age-matched normal subjects. The mean diffusivity (MD) values of putamen were also compared. Fisher's exact test, t-test, and one way analysis of variance were used to determine significance at corrected p < 0.05. RESULTS: HPR was observed in 38.5% of normal subjects. Age and gender predilection and laterality were not observed. In most cases, it occupied the full length or anterior half of the lateral margin of putamen, and was continuous throughout its length. Maximum transverse dimension was 2 mm. There was no association with hypointensity of nearby putamen. However, in MSA-P, HPR was located predominantly at the posterolateral aspect of putamen, and associated with putaminal atrophy. Discontinuity of HPR was more frequently observed in MSA-P. On visual analysis, the characteristics of HPR were similar between MSA-C patients and normal subjects. Patients with MSA of either type had significantly higher MD values of putamen than normal subjects. CONCLUSIONS: HPR can be observed in 38.5% of normal subjects at 1.5 T. Thin linear hyperintensity without discontinuity, occupying the full length or anterior half of the lateral margin of the putamen, is suggestive of "normal." In doubtful cases, measurement of the MD values of nearby putamen may be valuable.

Preoperative percutaneous transhepatic portal vein embolization with ethanol injection.
Yusuke Sakuhara, Daisuke Abo, Yu Hasegawa, Tadashi Shimizu, Toshiya Kamiyama, Satoshi Hirano, Daisuke Fukumori, Takeshi Kawamura, Yoichi M Ito, Khin Khin Tha, Hiroki Shirato, Satoshi Terae
AJR. American journal of roentgenology, 198, 4, 914, 22, AMER ROENTGEN RAY SOC, 2012年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVE: The purpose of this article is to evaluate the feasibility and efficacy of preoperative percutaneous transhepatic portal vein embolization with ethanol injection. MATERIALS AND METHODS: We retrospectively evaluated 143 patients who underwent percutaneous transhepatic portal vein embolization. Hypertrophy of the future liver remnant was assessed by comparing the volumetric data obtained from CT image data before and after percutaneous transhepatic portal vein embolization. The evaluation of effectiveness was based on changes in the absolute volume of the future liver remnant and the ratio of the future liver remnant to the total estimated liver volume. RESULTS: Ten of 143 patients (7.0%) underwent additional embolization because of recanalization and insufficient hypertrophy of the future liver remnant. The mean increase in the ratio of the future liver remnant was 33.6% (p < 0.0001), and the mean ratio of future liver remnant to total estimated liver volume increased from 34.9% to 45.7% (p < 0.0001). Although most of the patients complained of pain after ethanol injection, they were gradually relieved of pain in a few minutes by conservative treatment. Fever (38-39°C) was reported after 47 of 151 (31.1%) percutaneous transhepatic portal vein embolization sessions and was resolved within a few days. Transient elevation of the liver transaminases was observed after the procedures and resolved within about a week. Major complications occurred in nine of 151 (6%) percutaneous transhepatic portal vein embolization sessions, but no patients developed hepatic insufficiency or severe complications precluding successful resection. One hundred twenty patients underwent hepatic resection, and two patients developed hepatic failure after surgery. CONCLUSION: Preoperative percutaneous transhepatic portal vein embolization with ethanol is a feasible and effective procedure to obtain hypertrophy of the future liver remnant for preventing hepatic failure after hepatectomy.

Validation Study on the Accuracy of Echocardiographic Measurements of Right Ventricular Systolic Function in Pulmonary Hypertension
Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Noriko Oyama-Manabe, Asuka Yamada, Yoichi M. Ito, Chisa Goto, Taku Watanabe, Shinji Sakaue, Masaharu Nishimura
JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY, 25, 3, 280, 286, MOSBY-ELSEVIER, 2012年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: The accuracy of echocardiographic parameters of right ventricular (RV) function has not been sufficiently validated in patients with pulmonary hypertension (PH). The aim of this study was to evaluate whether echocardiographic measurements reliably reflect RV systolic function in PH using cardiac magnetic resonance imaging (CMRI)-derived RV ejection fraction (RVEF) as a gold standard.
Methods: A total of 37 consecutive patients with PH, 20 with pulmonary arterial hypertension, 12 with chronic thromboembolic PH, and five others, were prospectively studied. All patients underwent echocardiography, CMRI, and right-heart catheterization within a 1-week interval. Associations between five echocardiography-derived parameters of RV systolic function and CMRI-derived RVEF were evaluated.
Results: All five echocardiography-derived parameters were significantly correlated with CMRI-derived RVEF (percentage RV fractional shortening: r = 0.48, P = .0011; percentage RV area change: r = 0.40, P = .0083; tricuspid annular plane systolic excursion [TAPSE]: r = 0.86, P < .0001; RV myocardial performance index: r = -0.59, P < .0001; and systolic lateral tricuspid annular motion velocity: r = 0.63, P < .0001). Compared with the other indices, TAPSE exhibited the highest correlation coefficient. Of the five echocardiographic measurements, only TAPSE significantly predicted CMRI-derived RVEF in multiple regression analysis (P < .0001). Intraobserver and interobserver reproducibility was favorable for all five indices and was particularly high for TAPSE and systolic lateral tricuspid annular motion velocity.
Conclusions: Echocardiographic measurements are promising noninvasive indices of RV systolic function in patients with PH. In particular, TAPSE is superior to other indices in accuracy. (J Am Soc Echocardiogr 2012;25:280-6.)

Annual Change in Pulmonary Function and Clinical Phenotype in Chronic Obstructive Pulmonary Disease
Masaharu Nishimura, Hironi Makita, Katsura Nagai, Satoshi Konno, Yasuyuki Nasuhara, Masaru Hasegawa, Kaoruko Shimizu, Tomoko Betsuyaku, Yoichi M. Ito, Satoshi Fuke, Takeshi Igarashi, Yasushi Akiyama, Shigeaki Ogura
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 185, 1, 44, 52, AMER THORACIC SOC, 2012年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Rationale: Although the rate of annual decline in FEV1 is one of the most important outcome measures in chronic obstructive pulmonary disease (COPD), little is known about intersubject variability based on clinical phenotypes.
Objectives: To examine the intersubject variability in a 5-year observational cohort study, particularly focusing on emphysema severity.
Methods: A total of 279 eligible patients with COPD(stages I-IV: 26,45, 24, and 5%) participated. We conducted a detailed assessment of pulmonary function and computed tomography (CT) at baseline, and performed spirometry every 6 months before and after inhalation of bronchodilator. Smoking status, exacerbation, and pharmacotherapy were carefully monitored. Emphysema severity was evaluated by CT and annual measurements of carbon monoxide transfer coefficient.
Measurements and Main Results: Using mixed effects model analysis, the annual decline in post-bronchodilator FEV1 was -32 +/- 24 (SD) ml/yr (n = 261). We classified the subjects of less than the 25th percentile as Rapid decliners, the 25th to 75th percentile as Slow decliners, and greater than the 75th percentile as Sustainers (-63 +/- 2, -31 +/- 1, and -2 +/- 1 [SE] ml/yr). Emphysema severity, but not %FEV1, showed significant differences among the three groups. Multiple logistic regression analysis demonstrated that the Rapid decliners were independently associated with emphysema severity assessed either by CT or carbon monoxide transfer coefficient. The Sustainers displayed less emphysema and higher levels of circulating eosinophils.
Conclusions: Emphysema severity is independently associated with a rapid annual decline in FEV1 in COPD. Sustainers and Rapid decliners warrant specific attention in clinical practice.

Prenatal exposure to perfluorinated chemicals and relationship with allergies and infectious diseases in infants
Emiko Okada, Seiko Sasaki, Yasuaki Saijo, Noriaki Washino, Chihiro Miyashita, Sumitaka Kobayashi, Kanae Konishi, Yoichi M. Ito, Rie Ito, Ayako Nakata, Yusuke Iwasaki, Koichi Saito, Hiroyuki Nakazawa, Reiko Kishi
ENVIRONMENTAL RESEARCH, 112, 118, 125, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2012年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: Recent studies have shown effects of prenatal exposure to perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) on infants in the general environmental levels. Laboratory animal studies have shown that exposure to PFOS and PFOA is associated with immunotoxic effects.
Objectives: To investigate the relationship between maternal PFOS and PFOA levels and infant allergies and infectious diseases during the first 18 months of life. Cord blood immunoglobulin (Ig) E levels were also evaluated.
Methods: We conducted a prospective cohort study of pregnant women from 2002 to 2005 in Sapporo, Japan. Maternal PFOS and PFOA levels were measured in relation to cord blood IgE concentrations (n=231) and infant allergies and infectious diseases (n=343). Characteristics of mothers and their infants were obtained from self-administered questionnaires and medical records. Development of infant allergies and infectious diseases was determined from self-administered questionnaires at 18 months of age. Concentrations of PFOS and PFOA in maternal serum and concentrations of IgE in umbilical cord serum at birth were measured.
Results: Cord blood IgE levels decreased significantly with high maternal PFOA concentration among female infants. However, there were no significant associations among maternal PFOS and PFOA levels and food allergy, eczema, wheezing, or otitis media in the 18 month-old infants (adjusted for confounders).
Conclusions: Although cord blood IgE level decreased significantly with high maternal PFOA levels among female infants, no relationship was found between maternal PFOS and PFOA levels and infant allergies and infectious diseases at age in 18 months. (C) 2011 Elsevier Inc. All rights reserved.

Usefulness of portography and contrast-enhanced computed tomography to predict the embolized area in percutaneous transhepatic portal vein embolization with absolute ethanol under temporary balloon occlusion
Yu Hasegawa, Daisuke Abo, Yusuke Sakuhara, Fumi Kato, Tamotsu Kamishimma, Tadashi Shimizu, Yoichi M. Ito, Satoshi Terae, Hiroki Shirato
JAPANESE JOURNAL OF RADIOLOGY, 30, 1, 53, 61, SPRINGER, 2012年01月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, To assess the usefulness of portography and contrast-enhanced computed tomography (CECT) for predicting the embolized area after the first injection of absolute ethanol (AE) in right portal vein embolization (RPVE).
Portograms were retrospectively reviewed in 50 patients (30 men and 20 women, mean age 65 years) who had undergone percutaneous transhepatic RPVE with AE under temporary balloon occlusion (TBO) between February 2002 and October 2009. The enhancement pattern before embolization and the embolization pattern after the first AE injection were analyzed by portography. The angles of portal branches against the horizontal plane were measured in 48 patients using pre-treatment CECT.
The enhancement pattern was not consistent with the embolization pattern in 35 patients (p < 0.001). When the anterior branch angles were divided into two groups at -5A degrees, 0A degrees, 10A degrees, and 15A degrees, the frequency of the posterior-branch-dominant embolization pattern was higher in the more negatively angled group (p = 0.002-0.041).
The distribution of AE is different from that of contrast medium in percutaneous transhepatic RPVE under TBO. The pre-treatment measurement of the angles of portal branches against the horizontal plane on CECT is suggested to be useful for predicting the embolized area.

In vivo vascularity alterations in repaired rotator cuffs determined by contrast-enhanced ultrasound.
Tadanao Funakoshi, Norimasa Iwasaki, Tamotsu Kamishima, Mutsumi Nishida, Yoichi Ito, Kinya Nishida, Makoto Motomiya, Naoki Suenaga, Akio Minami
The American journal of sports medicine, 39, 12, 2640, 6, 2011年12月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: The alterations in blood flow after rotator cuff repair remain unclear. Visualization of vascular patterns could clarify basic and clinical investigations. PURPOSE: To assess longitudinal blood flow inside the repaired cuff and the surrounding tissue after rotator cuff repair, using contrast-enhanced ultrasonography. STUDY DESIGN: Descriptive laboratory study. METHODS: Fifteen patients (7 men and 8 women; mean age, 65.0 ± 9.8 years) consented to participate. The patients underwent an ultrasound scan before and 1, 2, and 3 months after surgery. Enhanced ultrasound images were recorded for 1 minute after intravenous injection of contrast reagent. Four regions of interest inside the cuff and 2 regions in the anchor hole and subacromial bursa were superimposed on the obtained images. Calculated areas under the time-intensity curves were expressed in acoustic units (AU). RESULTS: We found area-dependent differences in patterns of alteration and magnitude of blood flow inside the repaired cuff and peritendinous tissues. Vascularity in the articular distal and bursal distal region of the repaired cuff at 1 month postoperatively increased significantly compared with that at the preoperative baseline (76 vs 5 AU, P = .0037; 92 vs 7 AU, P = .043). The vascularity peaked at 1 month after surgery in the bursal area within the cuff but at 2 months in the articular area. The vascularity in the articular proximal region of the repaired cuff was significantly lower than that in the bursal proximal (P = .0046), bursal distal (P = .0183), and articular distal regions (P = .0163) 1 month after surgery. CONCLUSION: Enhancement patterns in intratendinous tissue increased at 1 or 2 months postoperatively and decreased at 3 months. We found area-dependent differences in enhancement patterns inside the repaired cuff and peritendinous tissue. CLINICAL RELEVANCE: Visualization of vascularization using contrast-enhanced ultrasound could help in deciding on an appropriate repair technique or on the form of postoperative rehabilitation after rotator cuff repair.

Identification and further differentiation of subendocardial and transmural myocardial infarction by fast strain-encoded (SENC) magnetic resonance imaging at 3.0 Tesla.
Noriko Oyama-Manabe, Naoki Ishimori, Hiroyuki Sugimori, Marc Van Cauteren, Kohsuke Kudo, Osamu Manabe, Tomoyuki Okuaki, Tamotsu Kamishima, Yoichi M Ito, Hiroyuki Tsutsui, Khin Khin Tha, Satoshi Terae, Hiroki Shirato
European radiology, 21, 11, 2362, 8, SPRINGER, 2011年11月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: To investigate whether subendocardial and transmural myocardial infarction can be identified and differentiated using the peak circumferential and longitudinal strains measured by fast strain-encoded (SENC). METHODS: Nineteen patients with ischemic heart diseases underwent imaging with fast SENC and late gadolinium enhancement (LGE) MRI at 3 T. Fast SENC measurements were performed in three short-axis slices (basal, mid-ventricular and apical levels) and one long-axis view (four-chamber) to assess peak longitudinal and circumferential systolic strains. RESULTS: All patients showed myocardial infarction with an average of 7 positive LGE segments. A total of 304 segments for longitudinal strains (LS) and 114 segments for circumferential strains (CS) could be analysed. Positive LGE segments showed lower peak CS and LS compared with the no LGE segments (P < 0.0001 for both). Segments with subendocardial infarction showed reduced CS and LS compared with the no LGE segments (P < 0.0001 for both). There was a significant difference in CS between subendocardial and transmural infarct segments (P = 0.03), but no significant difference in LS between them (P = 0.64). CONCLUSIONS: Fast SENC can identify old myocardial infarction and differentiate subendocardial from transmural infarction.

Early expression of plasma CCL8 closely correlates with survival rate of acute graft-vs.-host disease in mice.
Yamamoto M, Ota A, Hori T, Imai S, Sohma H, Suzuki N, Hatakeyama N, Inazawa N, Ito YM, Kimura H, Tsutsumi H, Kokai Y
Experimental hematology, 39, 11, 1101, 1112, ELSEVIER SCIENCE INC, 2011年11月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Objective. To elucidate the significance of early expression of CC-chemokine ligand motif 8 (CCL8) in mice with graft-vs.-host disease (GVHD), we investigated its induction mechanisms and correlation with overall survival rate in GVHD mice. Plasma CCL8 increases on day 5 of allogeneic transplantation, when signs of GVHD are barely detectable. Increase of allogeneic splenocytes in grafts exacerbates GVHD and leads to upregulation of plasma CCL8 on day 5. Overall survival is the gold standard in determining the severity of acute GVHD in mice, but the absence of clinical and/or pathological manifestations in the early phase make it difficult to estimate vital outcomes at this stage of allogeneic marrow transplantation.
Materials and Methods. After lethal irradiation, BALB/c mice received bone marrow transplantation from C57BL/6 mice. Survival rate was monitored and clinical and pathological scores of GVHD were examined. Coculture of BALB/c-derived dendritic cells and C57BL/6-derived splenocytes was performed. CCL8 was measured by immunoassay.
Results. The plasma CCL8 level at day 5 of transplantation was closely correlated with survival rate and clinical/pathological scores on day 14. In vitro study revealed that the BALB/c-derived dendritic cells expressed CCL8 upon stimulation of C57BL/6 CDC T cells by cell interactions through major histocompatibility complex class II molecules.
Conclusions. These investigations indicate that early and preclinical expression of CCL8 in plasma predicts overall survival of GVHD mice. Together with an involvement of allo-recognition in CCL8 expression, it suggests that CCL8 plays an important role in GVHD pathology. (C) 2011 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc.

Outcome of medium-dose VP-16/CY/TBI superior to CY/TBI as a conditioning regimen for allogeneic stem cell transplantation in adult patients with acute lymphoblastic leukemia
Akio Shigematsu, Junji Tanaka, Ritsuro Suzuki, Yoshiko Atsuta, Takakazu Kawase, Yoichi M. Ito, Takuya Yamashita, Takahiro Fukuda, Keiki Kumano, Koji Iwato, Fumiaki Yoshiba, Heiwa Kanamori, Naoki Kobayashi, Takashi Fukuhara, Yasuo Morishima, Masahiro Imamura
INTERNATIONAL JOURNAL OF HEMATOLOGY, 94, 5, 463, 471, SPRINGER TOKYO, 2011年11月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, The choice of conditioning regimen before allogeneic stem cell transplantation (SCT) in patients with acute lymphoblastic leukemia (ALL) is important. We retrospectively compared outcomes of medium-dose VP-16/cyclophosphamide/total body irradiation (VP/CY/TBI) regimen and CY/TBI. Five hundred and twenty-nine patients (VP/CY/TBI: n = 35, CY/TBI: n = 494) who met all of the following criteria were compared: first time for SCT, aged 15-59 years; first or second complete remission at SCT; bone marrow or peripheral blood as stem cell source; and HLA phenotypically matched donor. Median age of the patients was 34 years, and patients who received VP/CY/TBI were younger (28 vs. 34 years, P = 0.02). Cumulative incidences of relapse and non-relapse mortality (NRM) were higher for patients who received CY/TBI (P = 0.01 for relapse, P < 0.01 for NRM). After a median follow-up period of 36.9 months, 5-year overall survival (OS) rates were 82.2% in the VP/CY/TBI group and 55.2% in the CY/TBI group. OS, and disease-free survival (DFS) in the VP/CY/TBI group were shown to be significantly better by multivariate analysis [hazard ratio: 0.21 (95% confidence interval: 0.06-0.49) for DFS, hazard ratio: 0.25 (95% confidence interval: 0.08-0.59) for OS]. VP/CY/TBI was associated with a lower relapse rate and no increase in NRM, resulting in better survival than that in CY/TBI for adult ALL patients.

Model combining hydrodynamics and fractal theory for analysis of in vivo peripheral pulmonary and systemic resistance of shunt cardiac defects
Yoshihiro Nakamura, Shoichi Awa, Hitoshi Kato, Yoichi M. Ito, Akira Kamiya, Takashi Igarashi
JOURNAL OF THEORETICAL BIOLOGY, 287, 64, 73, ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 2011年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The fractal state of the arterial vascular tree is considered to have a universal dimension related to the principle of minimum work rate, but can demonstrate the capacity to adapt to other dimensions in disease states such as congenital high-flow pulmonary hypertension (PH) by a process that is incompletely understood. To document and interpret fractal adaptation in patients with different degrees of PH, pulmonary and systemic vascular resistance was analyzed by a model that evaluated the fractal dimension, x, of the Poiseuille resistance contribution of the arterial vessel radius between 10 and 100 mu m, via the proportionality Q proportional to(R(peri)/BL)(-x/4), with Q R(peri), and BL clinically observed variables representing total pulmonary or systemic blood flow, its peripheral arterial resistance, and body length, respectively. Identification of x in the pulmonary (P) and systemic (S) beds was evaluated from hemodynamic data of 213 patients, categorized into 7 groups by PH grade. In controls without PH, x(p)=2.2 while the dimension increased to 3.0, with the systemic dimension constant at x(s)=3.1. Our model predicts that severe grades of PH are associated with: a more elongated and hindered vessel in the periphery, and reductions in vessel numbers, as unit pulmonary resistive arterial trees (N(1)) and their component intra-acinar arteries (N(w)). These model network changes suggest a complex adaptive process of arterial network reorganization in the pulmonary circulation to minimize the work rate of high-flow congenital heart defects. (C) 2011 Elsevier Ltd. All rights reserved.

Apolipoprotein E4 Frequencies in a Japanese Population with Alzheimer's Disease and Dementia with Lewy Bodies
Seiju Kobayashi, Masaru Tateno, Tae Woo Park, Kumiko Utsumi, Hitoshi Sohma, Yoichi M. Ito, Yasuo Kokai, Toshikazu Saito
PLOS ONE, 6, 4, e18569, PUBLIC LIBRARY SCIENCE, 2011年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background: The apolipoprotein E (APOE) epsilon 4 allele has been reported to be a risk factor for Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Previous neuropathological studies have demonstrated similar frequencies of the APOE epsilon 4 allele in AD and DLB. However, the few ante-mortem studies on APOE allele frequencies in DLB have shown lower frequencies than post-mortem studies. One reason for this may be inaccuracy of diagnosis. We examined APOE genotypes in subjects with AD, DLB, and a control group using the latest diagnostic criteria and MRI, SPECT, and MIBG myocardial scintigraphy.
Methods: The subjects of this study consisted of 145 patients with probable AD, 50 subjects with probable DLB, and a control group. AD subjects were divided into two groups based on age of onset: early onset AD (EOAD) and late onset AD (LOAD). All subjects had characteristic features on MRI, SPECT, and/or myocardial scintigraphy.
Results: The rate of APOE4 carrier status was 18.3% and the frequency of the epsilon 4 allele was 9.7% in controls. The rate of APOE4 carrier status and the frequency of the epsilon 4 allele were 47% and 27% for LOAD, 50% and 31% for EOAD, and 42% and 31% for DLB, respectively.
Conclusion: The APOE4 genotypes in this study are consistent with previous neuropathological studies suggesting accurate diagnosis of AD and DLB. APOE4 genotypes were similar in AD and DLB, giving further evidence that the epsilon 4 allele is a risk factor for both disorders.

Single-slice epicardial fat area measurement: do we need to measure the total epicardial fat volume?
Noriko Oyama, Daisuke Goto, Yoichi M. Ito, Naoki Ishimori, Rie Mimura, Tomoo Furumoto, Fumi Kato, Hiroyuki Tsutsui, Nagara Tamaki, Satoshi Terae, Hiroki Shirato
JAPANESE JOURNAL OF RADIOLOGY, 29, 2, 104, 109, SPRINGER, 2011年02月, ［査読有り］
英語, 研究論文（学術雑誌）, The aim of this study was to assess a method for measuring epicardial fat volume (EFV) by means of a single-slice area measurement. We investigated the relation between a single-slice fat area measurement and total EFV.
A series of 72 consecutive patients (ages 65 +/- 11 years; 36 men) who had undergone cardiac computed tomography (CT) on a 64-slice multidetector scanner with prospective electrocardiographic triggering were retrospectively reviewed. Pixels in the pericardium with a density range from -230 to -30 Hounsfield units were considered fat, giving the per-slice epicardial fat area (EFA). The EFV was estimated by the summation of EFAs multiplied by the slice thickness. We investigated the relation between total EFV and each EFA.
EFAs measured at several anatomical landmarks-right pulmonary artery, origins of the left main coronary artery, right coronary artery, coronary sinus-all correlated with the EFV (r = 0.77-0.92). The EFA at the LMCA level was highly reproducible and showed an excellent correlation with the EFV (r = 0.92).
The EFA is significantly correlated with the EFV. The EFA is a simple, quick method for representing the time-consuming EFV, which has been used as a predictive indicator of cardiovascular diseases.

Prognostic Model for Hepatocellular Carcinoma with Time-Dependent Factors
Kenji Kuwaki, Kazuhiro Nouso, Yoshiyuki Kobayashi, Shinichiro Nakamura, Yoichi M. Ito, Shouta Iwadou, Hiroaki Hagihara, Tetsuya Yasunaka, Junichi Toshimori, Hirokazu Miyatake, Kenji Miyoshi, Hideki Onishi, Yasuhiro Miyake, Bon Shoji, Akinobu Takaki, Hidenori Shiraha, Yoshiaki Iwasaki, Haruhiko Kobashi, Kazuhide Yamamoto
ACTA MEDICA OKAYAMA, 65, 1, 11, 19, OKAYAMA UNIV MED SCHOOL, 2011年02月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, The purpose of this study was to build a prognostic model of hepatocellular carcinoma (HCC) using time-dependent covariates to re-evaluate the prognosis at any stage of the disease. The subjects were consecutive HCC patients who were treated at our institute between 1995 and 2007. We constructed time-fixed and time-dependent prognostic models with a training group (n = 336) and compared the prognostic abilities between conventional Cancer of the Liver Italian Program (CLIP) scores, Japan Integrated Staging (JIS) scores, an Okuda classification, and our prognostic models in the testing group (n = 227) with the c-index. The time-dependent prognostic model consisted of main tumor size, tumor number, portal vein invasion, distant metastasis, alpha-fetoprotein, des-gamma-carboxy prothrombin (DCP), bilirubin, and albumin and the weighted scores were set for each factor depending on the hazard ratio for the prognosis. The prognostic index was determined by summing the scores. The c-index values for the CLIP scores, JIS scores, Okuda classification, and our time dependent model were 0.741, 0.727, 0.609, and 0.870, respectively. These results indicate that our time-dependent model can estimate the prognosis of HCC more precisely than traditional time-fixed models and can be used to re-predict the prognosis of HCC.

Single-slice epicardial fat area measurement: do we need to measure the total epicardial fat volume?
Noriko Oyama, Daisuke Goto, Yoichi M Ito, Naoki Ishimori, Rie Mimura, Tomoo Furumoto, Fumi Kato, Hiroyuki Tsutsui, Nagara Tamaki, Satoshi Terae, Hiroki Shirato
Japanese journal of radiology, 29, 2, 104, 9, SPRINGER, 2011年02月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, PURPOSE: The aim of this study was to assess a method for measuring epicardial fat volume (EFV) by means of a single-slice area measurement. We investigated the relation between a single-slice fat area measurement and total EFV. METHODS AND METHODS: A series of 72 consecutive patients (ages 65 ± 11 years; 36 men) who had undergone cardiac computed tomography (CT) on a 64-slice multidetector scanner with prospective electrocardiographic triggering were retrospectively reviewed. Pixels in the pericardium with a density range from -230 to -30 Hounsfield units were considered fat, giving the per-slice epicardial fat area (EFA). The EFV was estimated by the summation of EFAs multiplied by the slice thickness. We investigated the relation between total EFV and each EFA. RESULTS: EFAs measured at several anatomical landmarks-right pulmonary artery, origins of the left main coronary artery, right coronary artery, coronary sinus-all correlated with the EFV (r = 0.77-0.92). The EFA at the LMCA level was highly reproducible and showed an excellent correlation with the EFV (r = 0.92). CONCLUSION: The EFA is significantly correlated with the EFV. The EFA is a simple, quick method for representing the time-consuming EFV, which has been used as a predictive indicator of cardiovascular diseases.

Detection of patient setup errors with a portal image - DRR registration software application
Kenneth Sutherland, Masayori Ishikawa, Gerard Bengua, Yoichi M. Ito, Yoshiko Miyamoto, Hiroki Shirato
JOURNAL OF APPLIED CLINICAL MEDICAL PHYSICS, 12, 3, 2, 15, MULTIMED INC, 2011年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The purpose of this study was to evaluate a custom portal image - digitally reconstructed radiograph (DRR) registration software application. The software works by transforming the portal image into the coordinate space of the DRR image using three control points placed on each image by the user, and displaying the fused image. In order to test statistically that the software actually improves setup error estimation, an intra-and interobserver phantom study was performed. Portal images of anthropomorphic thoracic and pelvis phantoms with virtually placed irradiation fields at known setup errors were prepared. A group of five doctors was first asked to estimate the setup errors by examining the portal and DRR image side-by-side, not using the software. A second group of four technicians then estimated the same set of images using the registration software. These two groups of human subjects were then compared with an auto-registration feature of the software, which is based on the mutual information between the portal and DRR images. For the thoracic case, the average distance between the actual setup error and the estimated error was 4.3 +/- 3.0 mm for doctors using the side-by-side method, 2.1 +/- 2.4 mm for technicians using the registration method, and 0.8 +/- 0.4 mm for the automatic algorithm. For the pelvis case, the average distance between the actual setup error and estimated error was 2.0 +/- 0.5 mm for the doctors using the side-by-side method, 2.5 +/- 0.4 mm for technicians using the registration method, and 2.0 +/- 1.0 mm for the automatic algorithm. The ability of humans to estimate offset values improved statistically using our software for the chest phantom that we tested. Setup error estimation was further improved using our automatic error estimation algorithm. Estimations were not statistically different for the pelvis case. Consistency improved using the software for both the chest and pelvis phantoms. We also tested the automatic algorithm with a database of over 5,000 clinical cases from our hospital. The algorithm performed well for head and breast but performed poorly for pelvis cases, probably due to lack of contrast in the megavoltage portal image. The software incorporates an original algorithm to fuse portal and DRR images, which we describe in detail. The offset optimization algorithm used in the automatic mode of operation is also unique, and may be useful if the contrast of the portal images can be improved.

In vivo visualization of vascular patterns of rotator cuff tears using contrast-enhanced ultrasound.
Tadanao Funakoshi, Norimasa Iwasaki, Tamotsu Kamishima, Mutsumi Nishida, Yoichi Ito, Makoto Kondo, Akio Minami
The American journal of sports medicine, 38, 12, 2464, 71, 2010年12月, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Hypoxia and decreased blood supply have been proposed as risks for tendon rupture. Visualization of the vascularity of intact and torn rotator cuffs would be useful for improving treatments for rotator cuff tear. PURPOSE: To assess vascularity inside a tendon or an adjacent rotator cuff insertion point in patients differing in age and extent of damage to the tendon. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: Ten volunteers (all men) and 15 patients (10 men, 5 women) consented to participate in the study. Contrast agent for enhanced ultrasound was injected intravenously. Enhanced ultrasound images of the torn cuff and the contralateral shoulder were recorded for 1 minute. Four small regions of interest, the articular and bursal sides of the tendon and the medial and lateral sides of the bursa, were studied in all shoulders. RESULTS: There was a significant decrease in blood flow in the intratendinous region in elderly subjects compared with young subjects, but age had no effect on blood flow in bursal tissue. Blood flow in ruptured rotator cuffs did not differ from that in intact rotator cuffs. The intraclass correlation coefficient for intraobserver reproducibility was 0.82 (95% confidence interval: 0.77-0.86). CONCLUSIONS: The findings of this investigation were the hypovascular pattern in intratendinous tissue compared with the subacromial bursa, the age-related decrease in intratendinous vascularity, and the hypovascular pattern in the tendon, regardless of rupture of the tendon. Clarification of vascular patterns inside or around the torn ends of a rotator cuff will assist in the development of successful treatments for torn rotator cuffs.

Investigation of Annexin A5 as a Biomarker for Alzheimer's Disease Using Neuronal Cell Culture and Mouse Model
Mami Yamaguchi, Yasuo Kokai, Shin-ichi Imai, Kumiko Utsumi, Kyoichi Matsumoto, Hirohito Honda, Yuka Mizue, Masako Momma, Tetsu Maeda, Shozo Toyomasu, Yoichi M. Ito, Seijyu Kobayashi, Eri Hashimoto, Toshikazu Saito, Hitoshi Sohma
JOURNAL OF NEUROSCIENCE RESEARCH, 88, 12, 2682, 2692, WILEY-LISS, 2010年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Alzheimer's disease (AD) differs from other forms of dementia in its relation to amyloid beta peptide (A beta). A beta, a proteolytic product of amyloid precursor proteins (APP), has a toxic effect on neuronal cells, which involves perturbation of their Ca(2+) homeostasis. This effect implies that changes of protein expression in neuronal cells with calcium stress should provide a molecular marker for this disease. In the present study, we used the supernatant from a neuronal cell culture after incubation with or without A beta and isolated a Ca(2+)-dependent acidic phospholipid binding fraction to perform a proteomic study. Several unique proteins were identified after incubation with A beta. We focused on annexin A5, among these proteins, because it binds both Ca(2+) and lipids likely to be involved in calcium homeostasis. Tg2576 transgenic mice (AD model) overexpressing mutant human APP showed a significant increase of annexin A5 in the brain cortex but not in other organs, including liver, kidney, lung, and intestine. In human plasma samples, the level of annexin A5 was significantly increased in a proportion of AD patients compared with a control group (P < 0.000) in the logistic regression analysis). From the receiver operating characteristic (ROC) curve with plasma annexin A5 concentrations, the mean area under the curve (AUC 0.898) suggests that annexin A5 is a favorable marker for AD. (C) 2010 Wiley-Liss, Inc.

Reduced intensity conditioning regimen with fludarabine, busulfan, and low-dose TBI (Flu-BU2-TBI): Clinical efficacy in high-risk patients
Mutsumi Takahata, Satoshi Hashino, Kohei Okada, Masahiro Onozawa, Kaoru Kahata, Junichi Sugita, Akio Shigematsu, Takeshi Kondo, Satoshi Yamamoto, Tomoyuki Endo, Mitsufumi Nishio, Yoichi M. Ito, Junji Tanaka, Takao Koike, Masahiro Asaka, Masahiro Imamura
AMERICAN JOURNAL OF HEMATOLOGY, 85, 4, 243, 248, WILEY-LISS, 2010年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Reduced intensity conditioning (RIC) regimens are widely used in allogeneic stem cell transplantation (SCT). In this study, we retrospectively investigated the clinical outcomes of RIC with fludarabine (Flu; 180 mg/m(2)), intravenous busulfan (BU; 6.4 mg/kg) or oral BU (8 mg/kg), and low-dose total body irradiation (TBI; 4 Gy) (Flu-BU2-TBI) in 66 patients (median age: 54.5 years) with various hematological malignancies. Thirty-eight patients (58%) were high-risk patients (median age: 56 years). The overall survival rate at 2 years of the high-risk patients was 64.5%, which was comparable to the survival rate of 70.9% in standard-risk patients (P = 0.68). The relapse rates at 2 years in the standard-risk and high-risk patients were 16 and 28%, respectively, and day 100 treatment-related mortality rates were 0 and 6%, respectively. The Flu-BU2-TBI regimen for high-risk patients showed therapeutic effects equivalent to those for standard-risk patients and favorable outcomes compared with those of other previous RIC regimens. Am. J. Hematol. 84:243-248, 2010. (C) 2010 Wiley-Liss, Inc.

The sensitivity and specificity of a new formula to distinguish endometrioid type endometrial carcinoma from ovarian endometrial carcinoma
Sadako Nishimura, Yoichi M. Ito, Hiroshi Tsuda, Yoshitaka Ohnishi, Fumio Kataoka, Hiroyuki Nomura, Tatsuyuki Chiyoda, Atsushi Suzuki, Nobuyuki Susumu, Daisuke Aoki, Masayuki Hatae
EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY, 148, 1, 67, 72, ELSEVIER SCIENCE BV, 2010年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Objectives: Endometrioid type adenocarcinoma sometimes occupies both endometrium and ovary and in some cases the origin cannot be determined.
Study design: In this study, we established a formula to distinguish ovarian endometrioid cancer (ECC) from endometrioid type endometrial cancer (EEC), based on our previous report of cyclin and KI67 expression pattern by immunohistochemistry of 36 EECc and 37 OECc by the logistic regression. We calculated the diagnostic accuracy using 92 test samples retrospectively and finally could diagnose the origin of 16 cases in whom endometrioid type adenocarcinoma arose in both ovary and endometrium and could be determined by Scully's criteria, and 15 cases in whom endometrioid type adenocarcinoma arose in both ovary and endometrium and Scully's criteria were not usuful retrospectively.
Results: The estimated formula is as follows: Logit(Prob(EOC)) = -1.1437 - 0.0853 CNA + 0.0423 CNB + 0.173 CND1 + 0.0129 CNE + 0.0224 CNF + 0.0508 KI67, where Prob(EOC) is the probability that a clinical sample is EOC. If Prob(EOC) is larger than 0.5, the diagnosis is ovarian cancer; if less than 0.5 it is endometrial cancer. Finally, using the formula, 37 of 48 EECs (77.1%) and 33 of 44 EOCs (75.0%) were correctly classified, with an accuracy of 76.1% (p < 0.0001), retrospectively. In 12 of the 16 cases (75%) who could be determined by Scully's criteria, the origin determined by Scully's criteria was concordant with the origin determined by the formula retrospectively. In the other 15 cases, 12 cases were judged as ovary/ovary, 2 cases were judged as uterus/uterus and 1 case was judged as uterus/ovary.
Conclusion: The formula we established was thought to be useful to distinguish the origin of the cases in whom endometrioid type adenocarcinoma arises in both ovary and endometrium. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Minimally Invasive Surgical Treatment for Tuberculous Spondylodiscitis
M. Ito, H. Sudo, K. Abumi, Y. Kotani, M. Takahata, M. Fujita, A. Minami
MINIMALLY INVASIVE NEUROSURGERY, 52, 5-6, 250, 253, GEORG THIEME VERLAG KG, 2009年10月, ［査読有り］
英語, 研究論文（学術雑誌）, The authors report the cases of 3 patients with tuberculous spondylodiscitis. All patients suffered from severe back or low back pain. Posterolateral endoscopic debridement and irrigation were performed followed by retention of a drainage tube at the affected sites. Additional puncture and drainage were conducted at the same time when extensive cold abscesses were identified around the paravertebral muscle. All patients experienced immediate pain relief postoperatively. This technique is effective for rapid pain relief and in obtaining neurological resolution for patients in the early stages of tuberculous spondylodiscitis and may also be a good method for preventing further vertebral collapse and kyphotic spinal deformity such as Gibbus vertebrae.

Managing "healthy" late preterm infants
Akio Ishiguro, Yoshiyuki Namai, Yoichi M. Ito
PEDIATRICS INTERNATIONAL, 51, 5, 720, 725, WILEY-BLACKWELL PUBLISHING, INC, 2009年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Background:
Late preterm infants are often managed in nursery rooms despite the risks associated with prematurity. The objective of this study was to determine the risks facing late preterm infants admitted to nursery rooms and to establish a management strategy.
Methods:
A total of 210 late preterm infants and 2648 mature infants were assessed. Infants born at 35 and 36 weeks' gestation weighing >= 2000 grams admitted to a nursery room and not requiring medical intervention at birth were of particular interest. The admission rates to the neonatal intensive care unit were evaluated according to the chart review.
Results:
Infants born at 35 and 36 weeks' gestation weighing >= 2000 grams had significantly higher admission rates than term infants at birth (Cochran-Mantel-Haenszel test, P < 0.001; common risk ratio, 4.27; 95% confidence interval, 2.41-7.55) and after birth (P < 0.001; common risk ratio, 3.57; 95% confidence interval, 2.40-5.33). More than 80% of admissions from the nursery room to the neonatal intensive care unit after birth were due to apnea or hypoglycemia in neonates born at 35 and 36 weeks' gestation. The admission rates due to apnea increased with decreasing gestational age. The admission rates due to hypoglycemia with no cause other than prematurity accounted for 24.3% of admissions for those born at 35 weeks' gestation and 14.1% of admissions for those born at 36 weeks' gestation; hypoglycemia due to other causes accounted for fewer admissions.
Conclusion:
The management strategy for late preterm infants should be individualized, based on apnea and hypoglycemia. The respiratory state of late preterm infants should be monitored for at least 2 days, and they should be screened for hypoglycemia on postnatal day 0.

Measurement of (63)Ni produced in Cu samples by the Hiroshima atomic bomb (vol 273, pg 517, 2007)
S. Shibata, K. Takamiya, Y. Ota, N. Nogawa, Y. Ito, T. Shibata, M. Hoshi, S. Endo, H. Hasai, S. Fujita
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY, 279, 2, 699, 699, SPRINGER, 2009年02月
英語, 研究論文（学術雑誌）

N1 component reflects difference of terminal chords in three-chord sequences
Shoko Dekio-Hotta, Tomoyuki Kojima, Shotaro Karino, Tatsuya Yamasoba, Itaru Dekio, Yoichi M. Ito, Hiroyuki Satake, Kimitaka Kaga
NEUROREPORT, 20, 3, 251, 256, LIPPINCOTT WILLIAMS & WILKINS, 2009年02月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, We understand from experience that musical contexts are formed when chords are combined according to the rules of harmony. In this study, the N1 component of the auditory-evoked potential was measured using comparable three-chord sequences; these sequences were constructed as a consecutive task (cf. C-C-C vs. Cm-Cm-Cm; control) and a cadence task (cf. C-G-C vs. C-G-Cm). In the cadence task, compared with cadences ending with a major chord (anticipated chord), those ending with a minor chord (unanticipated chord) showed a significantly larger amplitude of N1 waves. These components of auditory-evoked potentials reflect the effect of chord progression in musical perception and suggest that the musical context is recognized at least 100 ms after a chord is played. NeuroReport 20:251-256 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.

Role of multidrug resistance-associated protein 1 in the pathogenesis of allergic airway inflammation
Masakata Yoshioka, Hironori Sagara, Fumiyuki Takahashi, Norihiro Harada, Kazuto Nishio, Akio Mori, Hiroko Ushio, Kazue Shimizu, Takenori Okada, Mayumi Ota, Yoichi M. Ito, Osamu Nagashima, Ryo Atsuta, Toshihiro Suzuki, Takeshi Fukuda, Yoshinosuke Fukuchi, Kazuhisa Takahashi
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 296, 1, L30, L36, AMER PHYSIOLOGICAL SOC, 2009年01月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Yoshioka M, Sagara H, Takahashi F, Harada N, Nishio K, Mori A, Ushio H, Okada KS, Ota M, Ito YM, Nagashima O, Atsuta R, Suzuki T, Fukuda T, Fukuchi Y, Takahashi K. Role of multidrug resistance-associated protein 1 in the pathogenesis of allergic airway inflammation. Am J Physiol Lung Cell Mol Physiol 296: L30-L36, 2009. First published October 17, 2008; doi:10.1152/ajplung.00026.2008. -Multidrug resistance-associated protein 1 (MRP1) is a cysteinyl leukotriene (CysLT) export pump expressed on mast cells. CysLTs are crucial mediators in allergic airway disease. However, biological significance of MRP1 in allergic airway inflammation has not yet been elucidated. In this study, we sensitized wild-type control mice (mrp1(-/-)) and MRP1-deficient mice (mrp1(-/-)) to ovalbumin (OVA) and challenged them with OVA by aerosol. Airway inflammation and goblet cell hyperplasia after OVA exposure were reduced in mrp1(-/-) mice compared with mrp1(-/-) mice. Furthermore, CysLT levels in bronchoalveolar lavage fluid (BALF) from OVA-exposed mrp1(-/-) mice were significantly lower than those from OVA-exposed mrp1(-/-) mice. Levels of OVA-specific IgE, IL-4, and IL- 13 in BALF were also decreased in OVA-exposed mrp1(-/-) mice. IgE-mediated release of CysLTs from murine bone marrow-derived mast cells was markedly impaired by MRP1 deficiency. Our results indicate that MRP1 plays an important role in the development of allergic airway inflammation through regulation of IgE-mediated CysLT export from mast cells.

Factors Associated with Variation in Utility Scores among Patients with Prostate Cancer
Fumitaka Shimizu, Katsuki Fujino, Yoichi M. Ito, Takashi Fukuda, Yoshio Kawachi, Shigeru Minowada, Makoto Fujime, Yasuo Ohashi
VALUE IN HEALTH, 11, 7, 1190, 1193, BLACKWELL PUBLISHING, 2008年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Objective: We aimed to assess the effects of age, comorbidity, and disease-specific functions on utility scores derived from three methods on prostate cancer.
Methods: A total of 330 Japanese prostate cancer patients were asked to answer self-administered questionnaires. Community-weighted utility scores were derived from the EuroQoL-5D (EQ-5D) and the Short Form-36 (SF-36), while the patient's directly elicited utility score was derived from time trade-off technique. Univariate and multivariate analyses were performed to examine the relation between covariates and utility scores. We assigned age, the Index of Co-existent Disease, and disease-specific functions including sexual, urinary, bowel, and hormonal function as covariates.
Results: Bowel and hormonal function were related to utility scores, while age and sexual function were not. Comorbidities were more closely related to utility scores derived from EQ-5D and SF-36.
Conclusions: These results contribute to an understanding of which factor has an impact on utility scores in patients with prostate cancer.

A neural network approach to simple prediction of soil nitrification potential: A case study in Japanese temperate forests
Eriko Ito, Kenji Ono, Yoichi M. Ito, Makoto Araki
ECOLOGICAL MODELLING, 219, 1-2, 200, 211, ELSEVIER SCIENCE BV, 2008年11月
英語, 研究論文（学術雑誌）, The nitrogen status of forest ecosystems can be represented by the net nitrification potential (NNP) of the forest soils. Prediction of NNP using a small number of soil properties is a practically useful tool for forest management planning. Artificial neural networks (ANN) have recently become popular tools in forest modeling because they eliminate certain difficulties in handling forest data, such as the nonlinear relationships and non-normality. This study aimed to develop an ANN model to predict NNP that required a few soil properties as possible for input data. The ANN model was fitted to field data using the ridge-stabilized Gauss-Newton method, with a subset of methods to prevent excessively high weights that are likely to cause over-fitting. We collected surface mineral soil samples from 56 locations in temperate forest ecosystems of central Japan. We measured NNPs on a per area basis (Mg N km(-2)) using aerobic laboratory incubation at 30 degrees C for 4 weeks. The ANN-based model using data on only two soil properties (the C:N ratio and the maximum water-holding capacity) provided the best prediction of NNP. The ANN-based model's success results from its incorporation of (1) the nonlinear relationship between the C:N ratio and NNP and (2) the hierarchical control of NNP, which is governed primarily by the C:N ratio and secondarily by soil moisture conditions. The simplicity of the model greatly enhances its practical value in forest management planning. (C) 2008 Elsevier B.V All rights reserved.

Prognostic factors and treatment effects for hepatocellular carcinoma in Child C cirrhosis
K. Nouso, Y. M. Ito, K. Kuwaki, Y. Kobayashi, S. Nakamura, Y. Ohashi, K. Yamamoto
British Journal of Cancer, 98, 7, 1161, 1165, 2008年04月08日, ［査読有り］
英語, 研究論文（学術雑誌）, The aim of this study is to elucidate the prognostic factors and the treatment effect on survival in hepatocellular carcinoma (HCC) patients with Child C cirrhosis. Out of 3330 newly discovered HCC patients, 157 consecutive HCC individuals with Child C cirrhosis were enrolled. The prognostic factors were examined by Cox proportional hazards regression analysis and their survival was compared by propensity score-matched analysis. Multivariate analysis revealed that high serum bilirubin (>
3 mg dl-1), the presence of uncontrollable ascites, and a high platelet count (>
8 × 104 mm-3), so-called background liver factors, as well as multiple tumours, large tumours (>
3 cm), high alpha-fetoprotein (>
400 ng ml -1), and the presence of portal vein thrombus, so-called tumour factors, were factors of poor prognosis. While transcatheter arterial chemoembolisation (TACE) was a factor of good prognosis (relative risk=0.50, 95%CI=0.27-0.89, P=0.019), local ablation therapy and transcatheter arterial chemoinfusion (TAI) were not significant prognostic factors. The survival of patients who received TACE was superior to matched patients without active treatment (P=0.009)
however, we did not observe survival benefit after local ablation therapy or TAI. These results suggested that tumour factors as well as background liver factors are prognostic factors of HCC even in patients with Child C cirrhosis, and selective use of TACE in these patients provides survival benefit. © 2008 Cancer Research.

Sensitivity and specificity of des-gamma-carboxy prothrombin for diagnosis of patients with hepatocellular carcinomas varies according to tumor size
Shinichiro Nakamura, Kazuhiro Nouso, Kohsaku Sakaguchi, Yoichi M. Ito, Yasuo Ohashi, Yoshiyuki Kobayashi, Nobuyuki Toshikuni, Hironori Tanaka, Yasuhiro Miyake, Eiji Matsumoto, Yasushi Shiratori
AMERICAN JOURNAL OF GASTROENTEROLOGY, 101, 9, 2038, 2043, BLACKWELL PUBLISHING, 2006年09月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, OBJECTIVES: Serum levels of des-gamma-carboxy prothrombin (DCP) and alpha-fetoprotein (AFP) are known to be useful tumor markers for the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to examine the diagnostic efficacy of DCP and AFP in differentiating HCC from chronic liver diseases.
METHODS: We examined 1,377 HCC patients and 355 patients with chronic hepatitis or cirrhosis (non-HCC) who visited our institute and affiliated hospitals between June 1997 and September 2003.
RESULTS: The median values of DCP and AFP were 60 mAU/mL and 34 ng/mL in HCC patients, respectively, and 18 mAU/mL and 3 ng/mL in non-HCC patients, respectively. The areas under the receiver operating characteristic (ROC) curves of DCP and AFP were 0.812 and 0.887, respectively (p < 0.0001). The area under the DCP ROC curve was significantly smaller than that of AFP in tumors less than 3 cm in diameter (p < 0.0001). However, the ROC area of DCP was significantly larger than that of AFP in tumors greater than 5 cm in diameter (p < 0.0001).
CONCLUSIONS: The utility of DCP for the diagnosis of HCC was lower than that of AFP for small tumors, but higher than that of AFP for large tumors.

Prevalence of Epstein-Barr virus in Japan: Trends and future prediction
K Takeuchi, K Tanaka-Taya, Y Kazuyama, YM Ito, S Hashimoto, M Fukayama, S Mori
PATHOLOGY INTERNATIONAL, 56, 3, 112, 116, BLACKWELL PUBLISHING, 2006年03月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Epstein-Barr virus (EBV) is the causative agent of infectious mononucleosis and some malignancies including EBV-associated-lymphomas. A large portion of adults all over the world are infected with EBV. In children, however, there are geographic variations. Most of the children in Asia and in other developing countries are infected in their early life, before 1 year of age (> 90% of 5-9-year-old children are infected), while the age of primary infection is delayed in Western countries (approx. 50% of 5-9-year-old children are infected). The purpose of the present paper was to investigate the recent time trend of the EBV seropositivity among 5-7-year-old children living in Tokyo and its neighboring prefectures. Indirect immunofluorescein study for IgG antibody to viral capsid antigen was performed on 442 archival sera. Before the early 1990s, > 80% of 5-7-year-old children were found to be seropositive, while the positivity rate decreased to 59% (P < 0.001) for the years 1995-1999. These results also showed that the delay in the age of primary infection is continuing and that the rate is estimated to be < 50% in 2006. This result suggests that the delay will affect the incidence of EBV-associated disorders in Japan.

Identification of overexpression and amplification of ABCF2 in clear cell ovarian adenocarcinomas by cDNA microarray analyses
H Tsuda, YM Ito, Y Ohashi, KK Wong, Y Hashiguchi, WR Welch, RS Berkowitz, MJ Birrer, SC Mok
CLINICAL CANCER RESEARCH, 11, 19, 6880, 6888, AMER ASSOC CANCER RESEARCH, 2005年10月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Purpose: Patients with ovarian clear cell adenocarcinoma generally have a poor, response to combination chemotherapy and have overall poorer prognosis than patients with other histologic types of ovarian cancer. Genetic changes in this group of cancer have not been thoroughly explored. Identification of these changes may provide us new therapeutic targets to treat this disease.
Experimental Design: Genomic and expression array analyses were applied on 30 clear cell ovarian cancer cases and 19 serous cases using a 10,816-element cDNA microarray platform. Further validation and clinical correlation studies were done on differentially expressed genes that are related to chemo resistance.
Results: Based on array analyses, 12 genes showed a significant increase in DNA and mRNA copy number and 5 genes showed a significant decrease in DNA and RNA copy number in clear cell tumors compared with those in the serous type. One of the genes was ABCF2, which belongs to the ATP-binding cassette gene superfamily and has been shown to amplify in other tumor types. Validation studies were done using real-lime quantitative PCR and immunohistochemistry. The results showed significantly higher ABCF2 DNA and mRNA copy number and protein levels in clear cell cases compared with those in serous cases. Furthermore, in 20 clear cell cases with chemoresponse data available, ABCF2 cytoplasmic staining was significantly higher in nonresponders than that in the responders (60.0% versus 28.5%; P = 0.0002).
Conclusions: These data suggest that ABCF2 protein may be a prognostic marker for ovarian clear cell ovarian adenocarcinoma.

Burkholderia pickettii spondylitis
H Sudo, Y Hisada, M Ito, H Kotaki, A Minami
SPINAL CORD, 43, 8, 499, 502, NATURE PUBLISHING GROUP, 2005年08月, ［査読有り］
英語, 研究論文（学術雑誌）, Study design: Case report describing Burkholderia pickettii spondylitis in a healthy adult.
Objectives: To describe this very rare form of spondylitis and to discuss some of the difficulties in the diagnosis of B. pickettii spondylitis.
Setting: Department of Orthopaedic Surgery, Nayoro City General Hospital, Japan.
Methods: A 48-year-old woman presented with a complaint of severe back pain radiating from the right side of her chest. Plain radiographs of the spine showed osteolytic destruction of the right side of the T10 vertebral body at T10 level, with an involvement of the pedicle. Magnetic resonance image of the spine showed a low signal intensity from the T10 vertebral body on a T1-weighted image and an increased signal intensity on T2-weighted sequence image. These lesions were enhanced when a contrast medium was used. The patient underwent open biopsy and specimens were collected through the right pedicle.
Results: Diagnosis was established on the basis of direct identification of the microorganism. Histological findings were consistent with examination of B. pickettii spondylitis. Chemotherapy ( intravenous cefepime and per os minocycline) resulted in complete cure.
Conclusion: B. pickettii is widely distributed in aqueous sources in nature and has not previously been considered to be an aggressive pathogen towards humans. This case report will help to improve our understanding of the ecology and virulent pathogenicity of this organism. A biopsy is an essential and reliable method for the early etiologic diagnosis, which will lead to prevent the development of more severe complications such as spinal cord compression.

Alcohol consumption and colorectal cancer risk: Findings from the JACC study
K Wakai, M Kojima, K Tamakoshi, Y Watanabe, N Hayakawa, K Suzuki, S Hashimoto, M Kawado, S Tokudome, S Suzuki, K Ozasa, H Toyoshima, Y Ito, A Tamakoshi
JOURNAL OF EPIDEMIOLOGY, 15, S173, S179, JAPAN EPIDEMIOLOGICAL ASSOC, 2005年06月, ［査読有り］
英語, 研究論文（学術雑誌）, BACKGROUND: Because alcohol drinking is a potential risk factor for colorectal cancer, the trend in alcohol consumption in Japan may partly explain the increase in incidence and mortality rates of this malignancy until 1990-1995.
METHODS: We analyzed data from the Japan Collaborative Cohort Study. From 1988 to 1990, 23,708 men and 34,028 women, aged 40-79 years, completed a questionnaire on lifestyle factors including drinking habits. Incidence rate ratios (IRR) were estimated by using proportional hazards models.
RESULTS: During the mean follow-up of 7.6 years through December 1997, we documented 418 incidents of colon cancer and 211 of rectal cancer. Male ex- or current drinkers demonstrated a twofold risk for colon cancer compared with nondrinkers: the multivariate-adjusted IRR was 2.01 (95 % confidence interval [CI] 1.09-3.68) for ex-drinkers and 1.97 (95 % Cl: 1.28-3.03) for current drinkers. The dose-response relationship between alcohol consumption and the risk, however, was not clear. Female ex-drinkers were at an increased risk without statistical significance. For rectal cancer, we found a slightly lower risk in light current drinkers who consumed less than 22 g ethanol per day: the multivariate IRR was 0.61 (95 % Cl: 0.33-1.13) for men and 0.69 (95 % Cl: 0.27-1.74) for women. Although the IRR for all current drinkers was almost unity in men, an increasing trend in risk was detected with increasing alcohol consumption in current drinkers (trend p = 0.027).
CONCLUSIONS: Taking the findings from our study and other prospective investigations into consideration, more attention should be paid to alcohol consumption in the prevention of colon cancer in Japan.

Medical history of circulatory diseases and colorectal cancer death in the JACC study
Y Watanabe, K Ozasa, Y Ito, K Suzuki, M Kojima, S Suzuki, S Tokudome, K Tamakoshi, H Toyoshima, M Kawado, S Hashimoto, N Hayakawa, K Wakai, A Tamakoshi
JOURNAL OF EPIDEMIOLOGY, 15, S168, S172, JAPAN EPIDEMIOLOGICAL ASSOC, 2005年06月, ［査読有り］
英語, 研究論文（学術雑誌）, BACKGROUND: Host factors expressed by individual past medical history of hypertension, stroke, and myocardial infarction may have a relationship with colorectal cancer.
METHODS: As part of the Japan Collaborative Cohort Study (JACC Study) for the Evaluation of Cancer Risk sponsored by the Ministry of Education, Science, Sports and Culture of Japan (Monbusho), we conducted a follow-up study of 110,792 Japanese inhabitants aged 40-79 years to reveal the relationship of past medical history of hypertension, stroke, and myocardial infarction at the baseline in 19881990 with colorectal cancer death for about 10 years up to the end of 1999.
RESULTS: Past medical history of hypertension associated with an increased risk of female rectal cancer when analyzing all cancer cases with adjustment for age, body mass index, and exercise (hazard ratio [HR] = 1.97, 95 % confidence interval [CI]; 1.13-3.43). Past medical history of myocardial infarction was also an increased risk for female rectal cancer (HR = 3.05, 95 % Cl; 1.28-7.28). Females who had a medical history of stroke had increased risk of rectal cancer without statistical significance.
CONCLUSION: There was a positive association of past medical history of hypertension and myocardial infarction and an increased risk of rectal cancer in women.

Glucose intolerance and colorectal cancer risk in a nested case-control study among Japanese people
K Ozasa, Y Ito, K Suzuki, Y Watanabe, M Kojima, S Suzuki, S Tokudome, K Tamakoshi, H Toyoshima, M Kawado, S Hashimoto, N Hayakawa, K Wakai, A Tamakoshi
JOURNAL OF EPIDEMIOLOGY, 15, S180, S184, JAPAN EPIDEMIOLOGICAL ASSOC, 2005年06月, ［査読有り］
英語, 研究論文（学術雑誌）, BACKGROUND: Glucose intolerance may increase the risk of developing colorectal cancer.
METHODS: In a sero-epidemiological nested case-control study, conducted as part of the Japan Collaborative Cohort Study (JACC Study) for Evaluation of Cancer Risk, we measured serum glycoalbumin in 123 patients with colorectal cancer and 279 controls. Conditional logistic regression was used to evaluate the risk of colorectal cancer.
RESULTS: There were trends towards an association between high levels of glycoalbumin and an increased risk of colorectal cancer in men (odds ratio [OR] = 2.39; 95 % confidence interval [CI]; 0.896.36) and between high levels of glycoalbumin and a decreased risk of colorectal cancer in women (OR = 0.41; 95 % Cl, 0.14-1.04).
CONCLUSIONS: A high level of glycoalbumin may increase the risk of colorectal cancer in men. The finding that high levels of glycoalburnin in women decreased their risk of colorectal cancer was inconsistent with previous reports, and may have been the result of limitations in the procedure in selecting samples and statistical power.

Colorectal cancer and serum C-reactive protein levels: a case-control study nested in the JACC study
Y Ito, K Suzuki, K Tamakoshi, K Wakai, M Kojima, K Ozasa, Y Watanabe, M Kawado, S Hashimoto, S Suzuki, S Tokudome, H Toyoshima, N Hayakawa, K Kato, M Watanabe, Y Ohta, M Maruta, A Tamakoshi
JOURNAL OF EPIDEMIOLOGY, 15, S185, S189, JAPAN EPIDEMIOLOGICAL ASSOC, 2005年06月, ［査読有り］
英語, 研究論文（学術雑誌）, BACKGROUND: Recently, it has been hypothesized that inflammation increases the risk of colorectal cancer. We investigated whether serum levels of C-reactive protein (CRP), a biomarker of inflammation, are associated with colorectal cancer, using serum samples collected in the Japan Collaborative Cohort Study (JACC Study).
METHODS: We conducted a nested case-control study in the JACC Study, investigating the relationship between the risk for colorectal cancer and serum levels of CRP determined by a high-sensitivity CRP enzyme immunoassay. The subjects recruited were 141 patients with colorectal cancer (63 males and 78 females) and 327 controls with no history of cancer (148 males and 179 females). Each case of colorectal cancer was matched for sex, age and participating institution to 2 or 3 controls. We used t-test to analyze mean differences in CRP levels between colorectal cancer cases and controls. Odds ratios (ORs) and their 95 % confidence intervals (CIs) were calculated using a conditional logistic regression model after adjusting for the potential confounding factors.
RESULTS: Serum CRP levels were not clearly associated with the risk of colorectal cancer. The OR of the highest serum CRP levels was 1.18 (95 % Cl: 0.68-2.06) for colorectal cancer and 1.42 (95 % Cl: 0.73-2.74) for colon cancer, compared to subjects with lowest serum levels. The OR for incidence of colorectal cancer showed a similar trend, but the difference was not significant. Thus, high serum CRP levels did not appear to increase the risk of colorectal cancer.
CONCLUSIONS: The present results suggest that high serum CRP levels are not associated with the risk of colorectal cancer in the JACC Study.

Stability of frozen serum levels of insulin-like growth factor-I, insulin-like growth factor-II, insulin-like growth factor binding protein-3, transforming growth factor beta, soluble fas, and superoxide dismutase activity for the JACC study
Y Ito, K Nakachi, K Imai, S Hashimoto, Y Watanabe, Y Inaba, A Tamakoshi, T Yoshimura
JOURNAL OF EPIDEMIOLOGY, 15, S67, S73, JAPAN EPIDEMIOLOGICAL ASSOC, 2005年03月, ［査読有り］
英語, 研究論文（学術雑誌）, BACKGROUND: Subjects of the Japan Collaborate Cohort Study (JACC Study) gave peripheral blood samples collected between 1988 and 1990. We conducted to investigate whether levels of serum components measured after 9 years of frozen storage are stable or not.
METHODS: To assess the degradation of frozen serum components in the JACC Study, we compared levels of various components (IGF-I, IGF-II, IGFBP-3, TGF-beta 1, sFas, and total SOD activity) between fresh and stored sera collected from other inhabitants. Serum levels of constituents were measured by immunoradiometric assay (IGF-I, IGF-II and IGFBP-3), quantitative enzyme immunoassay (TGF-beta 1), enzyme-linked immuno-adsorbent assay (sFas), and an improved nitrite method (SOD activity).
RESULTS: The coefficients of variation for intra- and inter-assay precisions of the measurements were less than 9%. Levels of IGF-I, IGF-II, IGFBP-3, TGF-beta 1 and sFas in sera after storage for 9 years at 80 degrees C were similar to those of fresh sera newly collected from inhabitants. The distributions of serum IGF-I, IGF-II, IGFBIP-3, TGF-beta 1, sFas and SOD activity for specimens collected from different individuals tended to be similar to those of serum levels for frozen specimens collected from different individuals and stored for 9 years.
CONCLUSIONS: There was no statistically significant difference in distribution of measured values of IGF-I, IGF-II, IGFBP-3, TGF-beta 1, and sFas between newly collected sera and frozen specimens stored for 9 years. Thus, measurements of these serum constituents of specimens stored for the JACC Study can be reliably used in nested case-control study.

Serum levels of polyunsaturated fatty acids and risk of colorectal cancer: A prospective study
M Kojima, K Wakai, S Tokudome, K Suzuki, K Tamakoshi, Y Watanabe, M Kawado, S Hashimoto, N Hayakawa, K Ozasa, H Toyoshima, S Suzuki, Y Ito, A Tamakoshi
AMERICAN JOURNAL OF EPIDEMIOLOGY, 161, 5, 462, 471, OXFORD UNIV PRESS INC, 2005年03月, ［査読有り］
英語, 研究論文（学術雑誌）, To examine the relation between serum fatty acids and risk of colorectal cancer, the authors conducted a nested case-control study of 169 colorectal cancer cases and 481 controls matched by age and enrollment area as part of the Japan Collaborative Cohort Study. Serum samples were donated by subjects at baseline (between 1988 and 1990) and were stored at -80degreesC until 2002. Serum fatty acid levels were measured by using gas chromatography and were expressed as the weight percentage of total lipids. Conditional logistic regression analyses adjusted for lifestyle factors revealed that total omega-3 polyunsaturated fatty acids (odds ratio = 0.24, 95% confidence interval: 0.08, 0.76), alpha-linolenic acid (odds ratio = 0.39, 95% confidence interval: 0.16, 0.91), docosapentaenoic acid (odds ratio = 0.30, 95% confidence interval: 0.11, 0.80), and docosahexaenoic acid (odds ratio = 0.23, 95% confidence interval: 0.07, 0.76) all showed a significantly decreased risk for the highest versus the lowest quartile levels for colorectal cancer in men. For women, a weak negative association was observed between docosapentaenoic acid and colorectal cancer risk, although it was not statistically significant. No adverse effects of high serum levels of omega-6 polyunsaturated fatty acids on colorectal cancer risk were detected.

Quantitative assessment of regional myocardial flow reserve using Tc-99m-Sestamibi imaging - Comparison with results of O-15 water PET
T Tsukamoto, Y Ito, K Noriyasu, K Morita, C Katoh, H Okamoto, N Tamaki
CIRCULATION JOURNAL, 69, 2, 188, 193, BLACKWELL PUBLISHING ASIA, 2005年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Background The aims of this study were to develop a method for quantitative estimation of the myocardial blood flow index (MBFI) and myocardial flow reserve (MFR) of the whole left ventricle using (99m)technetium (Tc-99m)-sestamibi imaging.
Methods and Results Twenty-two patients with suspected coronary artery disease and 7 controls underwent both Tc-99m-sestamibi imaging and O-15 water positron emission tomography (PET). The global MBFI was calculated on the basis of the microsphere model from the ratio of the myocardial count to the area under the time-activity curve on the aortic arch. The regional MBFI was calculated from the relative distributions of Tc-99m-sestamibi uptake values. The regional MBFI and MFR (Tc-MFR) obtained using single-photon emission computed tomography were compared with the myocardial blood flow (MBF) and MFR (PET-MFR) obtained using PET as the gold standard. Regional MBFI significantly correlated with the MBF obtained using PET. Regional Tc-MFR also correlated with the regional PET-MFR, with some underestimation.
Conclusion These results indicate that regional MBF and MFR may be estimated by dynamic Tc-99m-sestamibi imaging and can be used for the early detection and estimation of the functional severity of coronary lesions without the need for a PET camera.

Perceived psychologic stress and colorectal cancer mortality: Findings from the Japan collaborative cohort study
M Kojima, K Wakai, S Tokudome, K Tamakoshi, H Toyoshima, Y Watanabe, N Hayakawa, K Suzuki, S Hashimoto, M Kawado, S Suzuki, Y Ito, A Tamakoshi
PSYCHOSOMATIC MEDICINE, 67, 1, 72, 77, LIPPINCOTT WILLIAMS & WILKINS, 2005年01月, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: The purpose of this research was to examine the relationship between perceived psychologic stress and colorectal cancer mortality in a prospective large-scale study. Methods: Between the years 1988 and 1990, 32,153 men and 45,854 women aged 40 to 79 years were enrolled. Participants completed a self-administered questionnaire that addressed demographic, lifestyle, and psychosocial characteristics. Subjects were subsequently followed for mortality until the end of 1999. Perceived psychologic stress was assessed using the question "Do you feel stress during your daily life?" The 4 possible responses, ranging from "little or none" (1) to "extreme" (4), were dichotomized as low (I or 2) or high (3 or 4) stress. Relative risks (RRs) with 95% confidence intervals (CIs) for colon and rectal cancer according to the perceived level of stress were estimated using Cox's proportional hazard model. Results: During the follow-up period (average, 9.6 years), 193 colon cancer deaths (96 men and 97 women) and 127 rectal cancer deaths (88 men and 39 women) were confirmed within the study group. Women who reported high stress had a 1.64-fold higher risk of colon cancer mortality (multivariate-adjusted RR, 1.64; 95% CI, 1.01-2.66) compared with those reporting low stress. There was no significant association between perceived stress and female rectal cancer or male colon and rectal cancer mortality. Conclusions: Perceived psychologic stress was weakly associated with increased mortality from colon cancer in women. No positive or inverse association was found in men. Further studies are needed to confirm our results.

Leptin is associated with an increased female colorectal cancer risk: A nested case-control study in Japan
K Tamakoshi, H Toyoshima, K Wakai, M Kojima, K Suzuki, Y Watanabe, N Hayakawa, H Yatsuya, T Kondo, S Tokudome, S Hashimoto, S Suzuki, M Kawado, K Ozasa, Y Ito, A Tamakoshi
ONCOLOGY, 68, 4-6, 454, 461, KARGER, 2005年, ［査読有り］
英語, 研究論文（学術雑誌）, Objective: To elucidate whether leptin is involved in the etiology of female colorectal cancer. Methods: A case-control study nested in the Japan Collaborative Cohort Study. We compared serum leptin levels in 58 cases of female colorectal cancer with those in 145 controls matched for study area and age. Data were analyzed using a conditional logistic regression model with adjustments for known risk factors for the development of colorectal cancer. Quintile cutoff points were determined on the distribution of leptin levels in cases and controls combined. Results: Serum geometric mean levels of leptin were 6.88 ng/ml in cases and 6.00 ng/ml in controls. The odds ratios of female colorectal cancer risk were 1.40 (95% confidence interval, Cl: 0.41-4.78) for the category of the second and third quintiles combined, and 4.84 (CI: 1.29-18.1) for the category of the fourth and fifth quintiles combined relative to the first quintile after adjustment for body mass index (BMI), life-style factors, reproductive factors, and hormonal variables including insulin-like growth factor and its binding protein. Conclusion: Our results suggest that leptin most likely increases the risk of female colorectal cancer substantially independent of BMI. Copyright (C) 2005 S. Karger AG, Basel.

Serum carotenoids, retinol, and tocopherols, and colorectal cancer risk in a Japanese cohort: Effect modification by sex for carotenoids
K Wakai, K Suzuki, Y Ito, M Kojima, K Tamakoshi, Y Watanabe, H Toyoshima, N Hayakawa, S Hashimoto, S Tokudome, S Suzuki, M Kawado, K Ozasa, A Tamakoshi
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 51, 1, 13, 24, LAWRENCE ERLBAUM ASSOC INC, 2005年, ［査読有り］
英語, 研究論文（学術雑誌）, To examine associations of serum carotenoids, retinol, and tocopherols with colorectal cancer risk, we conducted a case-control study nested within the Japan Collaborative Cohort Study. These micronutrients were measured in prediagnostic serum samples from 116 men and women who developed colorectal cancer during an 8-yr follow-up period and from 298. matched controls. In men, the higher level of serum total carotenoids was associated with a decreased risk: The multivariate-adjusted odds ratio (OR) for the highest vs. the lowest tertile was 0.34 (95% confidence interval [CI] = 0.11-1.00; trend P over tertiles = 0.040). In women, the higher levels of alpha- and beta-carotenes and total carotenoids were instead related to an increased risk: The corresponding ORs were 4.72 (95% C1 = 1.29-17.3), 2.00 (0.70-5.73), and 2.47 (0.73-8.34), respectively (trend P = 0.007, 0.040, and 0.064, respectively). We also found a somewhat decreasing risk with increased serum retinol in all subjects and alpha-tocopherol in men: The ORs (95% CI) for the highest tertiles were 0.29 (0.11-0.78; trend P over tertiles = 0.010) and 0.29 (0.07-1.17; trend P = 0.098), respectively. The effects of some carotenoids on colorectal cancer risk may be modified by sex or by factors associated with sex, including smoking and drinking habits.

Identification of DNA copy number changes in microdissected serous ovarian cancer tissue using a cDNA microarray platform
H Tsuda, MJ Birrer, YM Ito, Y Ohashi, M Lin, C Lee, WH Wong, PH Rao, CC Lau, RS Berkowitz, KK Wong, SC Mok
CANCER GENETICS AND CYTOGENETICS, 155, 2, 97, 107, ELSEVIER SCIENCE INC, 2004年12月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, We have established a method for using a cDNA array platform in combination with degenerate oligonucleotide primer polymerase chain reaction (DOP-PCR) and taramide signal amplification (TSA) to identify DNA copy number abnormalities (CNA) in cancer cell lines and cancer cells procured with laser-based microdissection. To determine the sensitivity and specificity for detecting single-copy gain and loss, receiver-operator curve analysis was performed on hybridization signal ratios generated from non-DOP and DOP amplified female and male DNA using a 10,816-element cDNA microarray. A cutoff value of 1.12 and 1.07 average signal ratio for X-chromosomal genes versus autosomal genes provided a sensitivity and specificity of 50 and 79%, respectively, for non-DOP amplified DNA and a sensitivity and specificity of 50 and 72%, respectively, for DOP amplified DNA. We used this approach to identify DNA copy number abnormalities in the ovarian cancer cell line OVCA633, which has previously been shown to have 12p amplification. Transcription profiling of OVCA633 was also performed. Two amplified and overexpressed genes located on 12p 11, KRAS2 and LRMP, were identified; these were validated with quantitative real-time PCR. Subsequently, the same approach was used to identify CNAs and gene expression alterations in 11 microdissected serous ovarian adenocarcinoma cases. Validated data revealed amplification and overexpression of ERBB3 and FOS and deletion and underexpression of KRT6 and APXL in more than 50% of the tissue samples. These results show the feasibility of using the cDNA array platform to identify changes in DNA and mRNA copy number simultaneously in microdissected tumor tissues. (C) 2004 Elsevier Inc. All rights reserved.

Regulation of mineral-to-matrix ratio of lumbar trabecular bone in ovariectomized rats treated with risedronate in combination with or without vitamin K-2
H Otomo, A Sakai, S Ikeda, S Tanaka, M Ito, RJ Phipps, T Nakamura
JOURNAL OF BONE AND MINERAL METABOLISM, 22, 5, 404, 414, SPRINGER TOKYO, 2004年09月, ［査読有り］
英語, 研究論文（学術雑誌）, The relationship between bone turnover and bone tissue and material properties was examined in ovariectomized (OVX) rats treated with risedronate in combination with or without vitamin K-2. Seventy female rats, 18 weeks of age, were assigned to 7 groups (n=10): sham-operated + vehicle control; OVX + vehicle control; OVX + risedronate 0.1, 0.5, or 2.5 mg/kg/day po; OVX + vitamin K-2 similar to30 mg/kg/day po; OVX + vitamin K-2 (similar to30 mg/kg/day) and risedronate (0.5 mg/kg/day). Treatments were given daily for 9 months. To assess bone turnover, we measured serum osteocalcin and urinary deoxypyridinoline at 0, 3, and 9 months. To assess vertebral and femoral tissue and material properties, bone mass, bone mineral density (BMD by DXA), trabecular bone structure (vertebra: 3D-muCT), cortical bone structure (femur: histomorphometry), biomechanical properties, and mineral properties (mineral-to-matrix and carbonate-to-phosphate ratios by Fourier transform infrared microspectroscopy) were measured ex vivo at 9 months. Ovariectomy increased bone turnover and induced significant loss of bone mass/density, structure, mineral properties (mineral-to-matrix ratio), and strength. Risedronate produced dose-dependent inhibition of the ovariectomy-induced increase in turnover and loss of bone mass/density, structure, mineral-to-matrix ratio, and strength, with a lowest effective dose of 0.1-0.5 mg/kg/day. High-dose risedronate (2.5 mg/kg/day) did not induce increases in any parameter above that of sham control. Vitamin K-2 had no effects. In the OVX groups, urinary deoxypyridinoline at 3 and 9 months correlated significantly with vertebral BMD, trabecular bone volume, ultimate load, stiffness, and mineral-to-matrix ratio, and with femoral BMD, cortical area, and ultimate load. These results support the concept that changes in bone tissue and material properties can result directly from changes in bone turnover. Different effects among different drugs on material properties, including mineral-to-matrix ratio, may reflect differences in the relative rate and magnitude of osteoclastic bone resorption and osteoblastic primary bone mineralization.

Validity and clinical applicability of the Japanese version of amyotrophic lateral sclerosis: Assessment questionnaire 40 (ALSAQ-40)
Takuhiro Yamaguchi, Sadayoshi Ohbu, Mari Saito, Yoichi Ito, Fumio Moriwaka, Kunio Tashiro, Yasuo Ohashi, Shun-Ichi Fukuhara
Brain and Nerve, 56, 6, 483, 494, 2004年06月, ［査読有り］
日本語, 研究論文（学術雑誌）, We studied validity and clinical applicability of the Japanese version of amyotrophic lateral sclerosis (ALS) assessment questionnaire 40 (ALSAQ-40). The original version contains forty questions measuring five areas (domains) of health status: Physical Mobility, ADL/ Independence, Eating and Drinking, Communication and Emotional Functioning. Data were obtained from 39 ALS patients and from their physicians at 15 centers in Japan. Patients completed the ALSAQ-40 and the SF-36, and provided information on their age and their status of ventilator use. Their physicians provided information on the date of diagnosis, type of disease and clinical characteristics, and ALSFRS-R. The patients' average age was 58.5 years, and 64% were men. The mean duration since diagnosis was 39.1 months. Forty four percent were classical ALS patients and 46% were receiving a respiratory intervention. Although there was much heterogeneity, the scores for Physical Mobility and ADL/Independence were higher (indicating worse health status) than the scores for the other domains. Item-scale correlations were strong, except for the item "felt embarrassed in social situations" in the Emotional Functioning domain. All the domains had very high internal consistency: Cronbach's alphas ranged 0.95 to 0.97. With regard to the cluster structure of the forty items, the Eating and Drinking domain and the Communication clustered together. The reason might be that the former consisted of only three items and both domains measure bulbar symptoms. Domain scores correlated significantly with scores of related dimensions in the SF-36 and ALSFRS-R, and did not correlate strongly with unrelated domains. The five items of the ALSAQ-5 correlated with all five domain scores on the ALSAQ-40. These results should be interpreted with caution because we analyzed together data from ALS patients with various characteristics. In conclusion, although we may need to add and remove some items and modify the wording of others, the Japanese version of the ALSAQ-40 had high validity and is likely to be useful in evaluating of QOL in ALS patients. Whether the ALSAQ-5 can be used in place of the ALSAQ-40 is a matter for further study.

A prospective study of body size and colon cancer mortality in Japan: The JACC Study
K Tamakoshi, K Wakai, M Kojima, Y Watanabe, N Hayakawa, H Toyoshima, H Yatsuya, T Kondo, S Tokudome, S Hashimoto, K Suzuki, Y Ito, A Tamakoshi
INTERNATIONAL JOURNAL OF OBESITY, 28, 4, 551, 558, NATURE PUBLISHING GROUP, 2004年04月, ［査読有り］
英語, 研究論文（学術雑誌）, OBJECTIVE: To determine whether body size measurements are risk factors for colon cancer death among the Japanese.
DESIGN AND SUBJECTS: A nationwide prospective study, the Japan Collaborative Cohort (JACC) Study from 1988 to 1999. The present analysis included 43 171 men and 58 775 women aged 40 - 79 y who respond to a questionnaire on current weight and height, weight around 20 y of age, and other lifestyle factors. Body mass index (BMI) at baseline and 20 y of age (B-BMI and 20-BMI, respectively) were calculated.
RESULTS: We identified 127 deaths from colon cancer during the follow-up of 424 698 person-years among men and 122 deaths during the follow-up of 591 787 person-years among women. After adjustments for the lifestyle factors known to modify the risk of colon cancer, weight at baseline showed a significant positive association in women, while no such association was seen in men. There was also a significant trend of increasing risk with the increase in B-BMI among women. Women with B-BMI greater than or equal to28 kg/m(2) had a relative risk (RR) of 3.41 (95% confidence interval (CI): 1.44 - 8.06) compared with those with BMI of 20- <22 kg/m(2). 20-BMI also presented the same trend of increasing risk as B- BMI. Women with 20-BMI of <22 and B-BMI of >26 kg/m(2), that is, excessive BMI gain, had a high RR of 3.41 (95% CI 1.29 - 9.02) compared with those with 20- BMI of <22 and B-BMI of <22 kg/m(2). There were no corresponding trends of colon cancer risk for B- BMI, 20- BMI, or BMI change among men.
CONCLUSIONS: These study data suggest that obesity and excessive weight gain are associated with the risk of colon cancer death in Japanese women but no such relationship was found in Japanese men.

Bowel movement frequency and risk of colorectal cancer in a large cohort study of Japanese men and women
M Kojima, K Wakai, S Tokudome, K Tamakoshi, H Toyoshima, Y Watanabe, N Hayakawa, K Suzuki, S Hashimoto, Y Ito, A Tamakoshi
BRITISH JOURNAL OF CANCER, 90, 7, 1397, 1401, NATURE PUBLISHING GROUP, 2004年04月, ［査読有り］
英語, 研究論文（学術雑誌）, The relationship between bowel movement (BM) frequency and the risk of colorectal cancer was examined in a large cohort of 25731 men and 37198 women living in 24 communities in Japan. At enrolment, each participant completed a self-administrated questionnaire on BM frequency and laxative use. Incidence rate ratios (IRR) with 95% confidence intervals (CI) were estimated using Cox's proportional-hazard model. During the follow-up period (average length 7.6 years), 649 cases of colorectal cancer, including 429 cases of colon cancer, were identified. Among women, subjects who reported a BM every 2-3 days had the lowest risk of developing colorectal (IRR=0.71, 95% CI=0.52-0.97) and colon cancer (IRR=0.70, 95% CI=0.49-1.00), whereas those reporting a BM every 6 days or less had an increased risk of developing colorectal (IRR=2.47, 95% CI=1.01-6.01) and colon cancer (IRR=2.52, 95% CI=0.93-6.82) compared with those reporting greater than or equal to1 BM per day. A similar, but nonsignificant, association between the frequency of BM and cancer risk was observed in men. There was no association between colorectal or colon cancer risk and laxative use. Regulating BM frequency might therefore have a role in the prevention of colorectal cancer.

UDP-glucuronosyltransferase 1A7 genetic polymorphisms are associated with hepatocellular carcinoma in Japanese patients with hepatitis C virus infection
Y Wang, N Kato, Y Hoshida, M Otsuka, H Taniguchi, M Moriyama, S Shiina, T Kawabe, YM Ito, M Omata
CLINICAL CANCER RESEARCH, 10, 7, 2441, 2446, AMER ASSOC CANCER RESEARCH, 2004年04月, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, Purpose: Genetic polymorphisms of UDP-glucuronosyl-transferase 1A7 (UGT1A7), which detoxifies endogenous and environmental carcinogens, have been reported to be associated with hepatocellular carcinoma (HCC) in German populations. On the other hand, we reported that interleukin-1beta (IL-1beta) gene polymorphisms were associated with hepatitis C virus (HCV)-related HCC. In this study, we evaluated the association of both genes with the risk of HCC in Japanese HCV-infected patients.
Experimental Design: Genetic polymorphisms of UGT1A7 and IL-1beta were investigated in 280 Japanese patients (122 with HCC and 158 without HCC) with chronic HCV infections, by use of standard PCR-based genotyping techniques.
Results: We designated the UGT1A7*1 allele (a haplotype conferring higher activity) as H and the *2, *3, and *4 alleles (haplotypes conferring lower activity) as L. The proportions of UGT1A7 L/L and H/L alleles (genotypes) in patients with HCC (25% and 45%, respectively) were higher than those in patients without HCC (15% and 39%, respectively) with odds ratios of 2.73 (95% confidence interval, 1.40-5.35) and 1.80 (95% confidence interval, 1.05-3.09), respectively, compared with the UGT1A7 H/H alleles. Multivariate analyses revealed that UGT1A7 L/L and IL-1beta/-31T/T-511C/C genotypes, the presence of cirrhosis, age 60 years, male sex, and alpha-fetoprotein >20 mug/ml were associated with the presence of HCC (odds ratios, 2.33, 2.67, 4.20, 3.12, 3.09, and 2.90, respectively).
Conclusion: The UGT1A7 polymorphisms together with IL-1beta were associated with the presence of HCC in Japanese HCV-infected patients.

A prospective study on the possible association between having children and colon cancer risk: Findings from the JACC Study
K Tamakoshi, K Wakai, M Kojima, Y Watanabe, N Hayakawa, H Toyoshima, H Yatsuya, T Kondo, S Tokudome, S Hashimoto, K Suzuki, Y Ito, A Tamakoshi
CANCER SCIENCE, 95, 3, 243, 247, JAPANESE CANCER ASSOC, 2004年03月, ［査読有り］
英語, 研究論文（学術雑誌）, If having children is regarded as an exposure in life, its effect on a host could be considered as being due to female sex hormones associated with pregnancy in women and some lifestyle factors associated with large families in both men and women. To explore the roles of having children in the etiology of colon cancer, we examined 36,629 women and 24,877 men aged 40-79 years who completed a questionnaire on the number of children and other lifestyle factors from 1988 to 1990 in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk. During 291,080 and 200,648 person-years of follow-up, we documented 198 female and 202 male incident colon cancers, respectively. After adjusting for some factors known or suspected to modify the risk of colon cancer, compared with the women with no children, the multivariate-adjusted relative risks of colon cancer were 0.74 (95% confidence interval [CI]: 0.30-1.84) for one child, 1.00 (95% Cl: 0.46-2.20) for two, 0.70 (95% Cl: 0.31-1.55) for three, and 0.59 (95% Cl: 0.26-1.33) for four or more. The risk of colon cancer showed a significantly monotonic decrease with increasing number of children (P value for trend=0.047). There was no association between the number of children and colon cancer risk among men. From these prospective data, having children may reduce risk of colon cancer among women, but not among men, suggesting that modifications of hormone profiles secondary to pregnancies may influence female colon cancer risk.

Diet and colorectal cancer mortality: Results from the Japan Collaborative Cohort Study
M Kojima, K Wakai, K Tamakoshi, S Tokudome, H Toyoshima, Y Watanabe, N Hayakawa, K Suzuki, S Hashimoto, Y Ito, A Tamakoshi
NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL, 50, 1, 23, 32, LAWRENCE ERLBAUM ASSOC INC, 2004年, ［査読有り］
英語, 研究論文（学術雑誌）, The relationship between diet and colorectal cancer mortality was analyzed in a prospective study of 45,181 men and 62,643 women aged 40-79 yr enrolled in the Japan Collaborative Cohort Study. Between 1988 and 1990, subjects completed a self-administered questionnaire on their sociodemographic characteristics, diet, and other lifestyle habits. During the follow-up period (average 9.9yr), 284 colon cancer deaths (138 men and 146 women) and 173 rectal cancer deaths (116 men and 57 women) were confirmed. The only significant association of colorectal cancer mortality with vegetable intake was observed between male rectal cancer mortality and green leafy vegetable consumption [hazard ratio (HR) using Cox proportional hazard models = 0.6; 95% confidence interval (CI) = 0.3-0.9; P for trend = 0.02]. Yogurt intake was also inversely associated with male rectal cancer mortality (HR = 0.5; 95% CI = 0.2-1.0; P for trend = 0.04). Egg consumption was positively associated with male colon cancer mortality (P for trend = 0.04). Women with high fruit consumption had increased colon cancer mortality (HR = 1.6; 95% CI = 1.0-2.6; P for trend = 0.04). It should be noted that this study lacked statistical power due to small sample size and measurement error in the food-frequency questionnaire. Further investigation is therefore necessary to confirm the association between diet and colorectal cancer especially by subsites and gender.

Effect of preoperative transbronchial biopsy on prognosis of non-small cell lung cancer
Jun Nakajima, Shinichi Takamoto, Jun Matsumoto, Eriho Takeuchi, Yoichi M. Ito
Asian Cardiovascular and Thoracic Annals, 12, 4, 330, 335, Asia Publishing Exchange Pte Ltd, 2004年, ［査読有り］, ［国際誌］
英語, 研究論文（学術雑誌）, The aim of this study was to examine the hypothesis that post-surgical prognosis of patients with non-small cell lung cancer (NSCLC) proven by preoperative transbronchial biopsy (TBLB) was inferior to that of patients with NSCLC determined at time of surgery. Patients with NSCLC undergoing complete resection were divided into two groups. Group 1: pathologic diagnosis determined by TBLB consisting of 335 cases, and Group 2 where TBLB was unsuccessful and exploratory thoracotomy or thoracoscopy was followed by surgical resection, consisting of 186 cases. The post-surgical recurrence-free rate and survival rate were significantly higher in Group 2 than Group 1. Recurrence-free survival rate of stage IA patients in Group 2 (93 cases) was also significantly higher than that of stage IA Group 1 patients (70 cases) ( p = 0.0018). Multivariate analyses demonstrated that positive TBLB yield was an independent negative determinant of prognosis in addition to pathologic staging and other clinicopathological factors. In conclusion, post-surgical prognosis of NSCLC patients was superior if preoperative TBLB was unsuccessful. This result suggested that advanced NSCLC had a tendency to be diagnosed with TBLB, and that the TBLB procedure might negatively impact the prognosis of patients with resectable NSCLC.

Smoking and colorectal cancer in a non-western population: a prospective Cohort Study in Japan
K Wakai, N Hayakawa, M Kojima, K Tamakoshi, Y Watanabe, K Suzuki, S Hashimoto, S Tokudome, H Toyoshima, Y Ito, A Tamakoshi
JOURNAL OF EPIDEMIOLOGY, 13, 6, 323, 332, JAPAN EPIDEMIOLOGICAL ASSOC, 2003年11月, ［査読有り］
英語, 研究論文（学術雑誌）, BACKGROUND: The risk of colorectal cancer in relation to smoking habits has been examined mostly in Caucasians, and evidence for other ethnic groups is still scarce.
METHODS: Our data came from the Japan Collaborative Cohort (JACC) Study. From 1988 through 1990, 25,260 men and 34,619 women aged 40-79 years completed a questionnaire on cigarette smoking and other lifestyle factors. Hazard ratios (HR) were estimated by fitting proportional hazards models.
RESULTS: During the mean follow-up of 7.6 years through December 1997, we documented 408 incident colon cancers and 204 rectal cancers. We found a non-significant increase in colon cancer risk in male current smokers compared with never smokers. The multivariate-adjusted hazard ratios were 1.07 (95% confidence interval [CI]: 0.72-1.59) for ex-smokers and 1.23 (95% CI: 0.85-1.78) for current smokers. We however failed to observe a clear dose-response relationship between smoking intensity or duration and colon cancer risk. The adjusted hazard ratio was 1.07 (95% CI: 0.71-1.61) even for 40+ years of smoking. Almost no increase in colon cancer risk was detected for female smokers, and male smokers were not at an enhanced risk of rectal cancer.
CONCLUSIONS: Cigarette smoking was not a strong risk factor for colorectal cancer even after a long-term exposure, although a weak association remains open to discussion.

In vitro biomechanical effects of reconstruction on adjacent motion segment: comparison of aligned/kyphotic posterolateral fusion with aligned posterior lumbar interbody fusion/posterolateral fusion
H Sudo, Oda, I, K Abumi, M Ito, Y Kotani, Y Hojo, A Minami
JOURNAL OF NEUROSURGERY, 99, 2, 221, 228, AMER ASSOC NEUROLOGICAL SURGEONS, 2003年09月, ［査読有り］
英語, 研究論文（学術雑誌）, Object. Posterior lumbar interbody fusion (PLIF) was developed to overcome the limitations of posterolateral fusion in correcting spinal deformity and maintaining lumbar lordosis. In this study the authors compare the biomechanical effects of three different posterior reconstructions on the adjacent motion segment.
Methods. Ten calf spinal (L2-S1) specimens underwent nondestructive flexion-extension testing (+/- 6 Nm). The specimens were destabilized at the L5-S1 levels after intact testing. This was followed by pedicle screw fixation with and without interbody cages as follows: 1) with straight rods ("aligned" posterolateral fusion); 2) with kyphotically prebent rods ("kyphotic" posterolateral fusion); and 3) with interbody cages combined with straight rods ("aligned" PLIF/posterolateral fusion). The range of motion (ROM) of the operative segments, the intradiscal pressure (IDP), and longitudinal lamina strain in the superior adjacent segment (L4-5) were analyzed.
The ROM associated with aligned PLIF/posterolateral fusion-treated specimens was significantly less than both the aligned and kyphotic posterolateral fusion-treated procedures in both flexion and extension loading (p < 0.05). The aligned PLIF/posterolateral fusion was associated with greater IDP and the lamina strain compared with the aligned and kyphotic posterolateral fusion groups in flexion loading. Under extension loading, greater IDP and lamina strain were present in the kyphotic posterolateral fusion group than in the aligned posterolateral fusion group. The highest IDP and lamina strain were shown in the aligned PLIF/posterolateral fusion group.
Conclusions. Compared with kyphotic posterolateral fusion, PLIF may lead to even higher load at the superior adjacent level because of the increased stiffness of the fixed segments even if local kyphosis is corrected by PLIF.

A moving middle finger
H Sudo, M Ito, A Minami
LANCET, 361, 9376, 2202, 2202, LANCET LTD, 2003年06月, ［査読有り］
英語

Reduction of coronary flow reserve in areas with and without ischemia on stress perfusion imaging in patients with coronary artery disease: A study using oxygen 15-labeled water PET
K Yoshinaga, C Katoh, K Noriyasu, Y Iwado, H Furuyama, Y Ito, Y Kuge, T Kohya, A Kitabatake, N Tamaki
JOURNAL OF NUCLEAR CARDIOLOGY, 10, 3, 275, 283, MOSBY, INC, 2003年05月, ［査読有り］
英語, 研究論文（学術雑誌）, Background. Myocardial perfusion single photon emission computed tomography (SPECT) occasionally fails to detect coronary stenosis in patients with coronary artery disease (CAD). We evaluated coronary flow reserve (CFR) using oxygen 15-labeled water in areas with and without ischemia on technetium 99m tetrofosmin stress perfusion SPECT in patients with angiographically documented CAD.
Methods and Results. Twenty-seven patients with CAD and eleven age-matched normal subjects were studied. Baseline myocardial blood flow (MBF),and MBF during hyperemia induced by intravenous adenosine triphosphate infusion (0.16 mg (.) kg(-1) (.) min(-1)) were determined with the use of O-15-labeled water positron emission tomography, and the CFR was calculated. Tc-99m tetrofosmin stress/rest SPECT was performed for comparison. On the basis of the results of coronary angiography and SPECT, coronary segments were divided into 3 types: segments with coronary stenosis and a perfusion abnormality on stress SPECT imaging (group A, n = 16), segments with coronary stenosis without a perfusion abnormality (group B, n = 42), and remote segments with no coronary stenosis or perftision abnormality (group C, n 18). Baseline MBF values were similar among the 3 groups. CFR in group A was lower (1.82 +/- 0.54) than in group B (2.22 +/- 0.87, P < .05), in group C (2.92 +/- 1.21, P < .01), and in normal segments (3.86 +/- 1.24, P < .001). CFR in group B was lower than in group C (P < .02) and in normal segments (P < .001). CFR in group C was lower than in normal segments (P < .02).
Conclusions. Areas with a perfusion abnormality on stress SPECT had reduced CFR. In the areas without a perfusion abnormality and with coronary stenosis, lowering of CFR was intermediate between the areas with a perfusion abnormality and remote segments. Moreover, CFR was slightly, but significantly, lower in remote segments in patients with CAD compared with normal segments.

[Validation of the Japanese version of the Parkinson's Disease Questionnaire].
Kohmoto J, Ohbu S, Nagaoka M, Suzukamo Y, Kihira T, Mizuno Y, Ito YM, Hith M, Yamaguchi T, Ohashi Y, Fukuhara S, Kondo T
Rinsho shinkeigaku = Clinical neurology, 43, 3, 71, 76, 2003年03月, ［査読有り］, ［国内誌］
日本語, 研究論文（学術雑誌）, UNLABELLED: The PDQ-39 (Parkinson's Disease Questionnaire-39) is a specific quality-of-life (QOL) scale for patients with Parkinson's disease (PD). It evaluates the dysfunction of daily living and quality of life. We developed the Japanese-translated version of PDQ-39 and examined the validity of the PDQ-39 in Japanese PD patients. SUBJECTS: A total of 156 patients with PD were studied (age 35-86 years, Hoehn-Yahr stage 1 to 4). None of the patients had dementia. METHODS: Semi-structured interviews were conducted by one trained interviewer. The PDQ-39, SF-36 (36-item short form of the Medical Outcome Study questionnaire), EQ5D (Euro Qol), and NAS-J (Nottingham Adjustment Scale Japanese version) were used for evaluation. The attending physician of each patient rated the patient's condition by using the UPDRS (Unified Parkinson's Disease Rating Scale). RESULTS: Exploratory factor analysis, Cronbach alpha, and construct validity were fair, and there were significant correlations between the results of the PDQ-39 and the corresponding parts of the UPDRS and SF-36, and the Hoehn-Yahr stage, respectively. CONCLUSION: The Japanese version of the PDQ-39 is valuable for evaluating the QOL of Japanese patients with PD. Results of comparison of PDQ-39 with other scales of the QOL such as NAS-J suggest the possibility that acceptance of the disease and feelings of self-achievement improve the QOL of patients with Parkinson's disease.

Altered myocardial flow reserve and endothelial function late after Kawasaki disease
H Furuyama, Y Odagawa, C Katoh, Y Iwado, Y Ito, K Noriyasu, M Mabuchi, K Yoshinaga, Y Kuge, K Kobayashi, N Tamaki
JOURNAL OF PEDIATRICS, 142, 2, 149, 154, MOSBY-ELSEVIER, 2003年02月, ［査読有り］
英語, 研究論文（学術雑誌）, Objectives Coronary arterial lesions after Kawasaki disease (KD) may cause coronary endothelial dysfunction as the result of intimal hypertrophy. Our purpose was to assess myocardial flow reserve (MFR) and endothelial function in various myocardial regions after KD by using positron emission tomography.
Study design Twenty-seven patients, 17.2 +/- 3.2 years of age, who had KD at 1.9 +/- 1.4 years, and 12 normal healthy subjects, 26.5 +/- 3.4 years of age, were evaluated by means of myocardial blood flow (MBF) with O-15-water positron emission tomography. MFR was estimated by MBF changes under adenosine triphosphate infusion and endothelial function by MBF changes under cold pressor testing. The left ventricle was divided into three coronary territories. Ten stenotic regions, 20 aneurysmal regions, 30 regressed aneurysmal regions, and 21 regions without coronary arterial lesions were compared with 36 control regions of the normal volunteers.
Results MBF at rest was similar in each region. Hyperemic blood flow and MFR in each region after KD was significantly lower than those in the regions of normal volunteers. MBF during cold pressor testing was significantly reduced in each region after KD, as compared with no change in the control regions.,
Conclusions Our study indicates impaired MFR and endothelial function regardless of coronary artery status after KD.

Spinal cord compression by multistrand cables after solid posterior atlantoaxial fusion - Report of three cases
H Sudo, K Abumi, M Ito, Y Kotani, A Minami
JOURNAL OF NEUROSURGERY, 97, 3, 359, 361, AMER ASSOC NEUROLOGICAL SURGEONS, 2002年10月, ［査読有り］
英語, 研究論文（学術雑誌）, The sublaminar wiring procedure has been commonly used for stabilizing the atlantoaxial complex. Multistrand braided cables were introduced in the early 1990s. In previous biomechanical studies these cables were demonstrated to be superior to monofilament wires in terms of their flexibility, mechanical strength, and fatigue-related characteristics. To the authors' knowledge, they are the first to describe clinically the occurrence of delayed spinal cord compression resulting from multistrand cables after the completion of rigid spinal arthrodesis in the upper cervical spine.
Three patients underwent posterior atlantoaxial fusion in which two sublaminar multistrand cables were placed. Between 15 and 48 months postoperatively, they suffered from upper- and lower-extremity numbness as well as gait disturbance. Plain radiography and computerized tomography myelography revealed spinal cord compression caused by the sublaminar cables, although fusion was complete and physiological alignment was maintained at the fused segment. The radiographs obtained immediately after surgery demonstrated that the initial cable placement had been properly performed. The shape of the cable at the initial surgery was oval and then gradually became circular. The anterior are of the circular shape of the cable in fact led to the spinal cord compression.
Considering the mechanism of this late complication, a cable tends to spring open because of its high flexibility and becomes circular shaped even after the complete arthrodesis. When applying multistrand cables for intersegmental fixation at the atlantoaxial complex, delayed complications related to bowing of the cables is possible.

QOL質問票における項目反応理論に対するパラメータ推定
伊藤 陽一, 大橋 靖雄
計量生物学, 23, 1, 3, 26, The Biometric Society of Japan, 2002年09月30日
日本語, Item Response Theory (IRT) is a promising concept for constructing and calibrating health related quality of life questionnaires. The most popular IRT model is the two-parameter logistic model, and its parameters are often estimated by the Marginal Maximum Likelihood method (MML). However, performance of estimation by MML is poor in a small sample, such as severe or rare disease patients. The purpose of this study was to propose a Bayesian method for improving the performance and to compare the precision and accuracy of estimates by different methods with a simulation. In the simulation, item responses were generated according to the two-parameter logistic model. The estimates obtained using a MML Program (MULTILOG) and a Bayesian program written in this study were compared with respect to the precision and accuracy. The proposed method could improve the performance about difficulty parameters using more than 100 individuals and 10 items. Though that about discrimination parameters was still poor. For example, 137 patients received the Parkinson's disease specific questionnaire (PDQ-39) and a generic one (SF-36); and we calibrated items of physical functioning in these questionnaire simultaneously. It was shown that half of the PDQ-39 items could measure the ability of patients at a little bit high level of physical functioning more efficiently than SF-36.

Quantitative analysis of regional wall motion and thickening by quantitative gated SPECT comparison with visual analysis
M Konno, K Morita, Adach, I, Y Ito, T Kohya, A Kitabatake, E Tsukamoto, N Tamaki
CLINICAL NUCLEAR MEDICINE, 26, 3, 202, 207, LIPPINCOTT WILLIAMS & WILKINS, 2001年03月, ［査読有り］
英語, 研究論文（学術雑誌）, Purpose: Electrocardiograph-gated myocardial SPECT permits a quantitative assessment of global and regional functions by quantitative gated SPECT software. To validate quantitative indexes of wall motion and wall thickening, the authors compared these indexes with visual scores,
Materials and Methods: Gated myocardial SPECT was performed 60 minutes after the administration of Tc-99m sestamibi at rest in 42 patients with coronary artery disease. Regional wail motion (measured in millimeters and wall thickening (expressed as a percentage) were calculated by quantitative gated SPECT software in nine left ventricular myocardial segments and the results were compared with the five-point visual score interpretations of cinematic display.
Results: A high correlation of wall motion was observed between the quantitative and visual analyses (r = 0.810; P < 0.001). In addition, a high but somewhat less significant correlation of wall thickening was observed between the quantitative and visual analyses (r = 0.606; P < 0.001).
Conclusions: In conclusion, regional wall motion and wall thickening can be evaluated quantitatively by electrocardiograph-gated myocardial SPECT and quantitative gated SPECT software. This will be useful for functional assessments made with various interventions.

Preparation of highly unsaturated fatty acid-containing phosphatidylcholine by transesterification with phospholipase A(2)
M Hosokawa, M Ito, K Takahashi
BIOTECHNOLOGY TECHNIQUES, 12, 8, 583, 586, KLUWER ACADEMIC PUBL, 1998年08月, ［査読有り］
英語, 研究論文（学術雑誌）, To prepare phospholipids containing highly unsaturated fatty acids (HUFA) by a one-step enzymatic reaction, 14 mu mol soy phosphatidylcholine (soy PC) in combination with 60 mu mol HUFA as acyl donor were transesterified with porcine pancreatic phospholipase A(2). Specify HUFA was successively incorporated into the sn-2 position of soy PC by this reaction at greater than 70% of total fatty acids at sn-2.

cT1腎癌に対する開腹腎部分切除術と鏡視下腎部分切除術後のSF-36を用いたQOLの比較　　　　　　　　　　　　　　　
大澤 崇宏, 安部 崇重, 菊地 央, 松本 隆児, 宮島 直人, 土屋 邦彦, 丸山 覚, 伊藤 陽一, 村井 祥代, 篠原 信雄, 泌尿器外科, 32, 7, 985, 986, 2019年07月
医学図書出版(株), 日本語

NORTH/HGCSG1003 Stage III結腸癌に対する術後補助化学療法FOLFOXの第II相研究 腫瘍内科医と外科医の比較　　　　　　　　　　　　　　　
村中 徹人, 小松 嘉人, 結城 敏志, 川本 泰之, 高橋 典彦, 七戸 俊明, 久須美 貴哉, 中村 文隆, 大森 一吉, 伊藤 陽一, 武冨 紹信, 平野 聡, 坂本 直哉, 日本大腸肛門病学会雑誌, 72, 1, 48, 48, 2019年01月
(一社)日本大腸肛門病学会, 日本語

日本における臨床研究の現状と,観察データに基づく臨床研究 リアルワールドデータの利用　　　　　　　　　　　　　　　
伊藤 陽一, 統計数理研究所データ科学研究系, 公衆衛生, 82, 12, 907, 11, 2018年12月
記事・総説・解説・論説等（学術雑誌）

Bladder Cancer Index(BCI)日本語版の開発におけるPilot Study　　　　　　　　　　　　　　　
大澤 崇宏, ウェイ・ジョン, 伊藤 陽一, 成田 学, 賀古 勇輝, 宮田 遙, 菊地 央, 松本 隆児, 宮島 直人, 丸山 覚, 安部 崇重, 村井 祥代, 篠原 信雄, 日本泌尿器科学会総会, 106回, PP1, 201, 2018年04月
(一社)日本泌尿器科学会総会事務局, 日本語

放射線治療における数値指標の医学物理的利用
清水伸一, 小橋啓司, 伊藤陽一, PRAYONGRAT Anussara, 加藤徳雄, 安田耕一, 出倉康裕, 木元拓也, 白土博樹, 日本放射線腫瘍学会高精度放射線外部照射部会学術大会プログラム・抄録集, 31st (CD-ROM), 39, 2018年
日本語

北海道における多系統萎縮症レジストリ研究:HoRC-MSA2014-2017　　　　　　　　　　　　　　　
松島 理明, 佐久嶋 研, 矢部 一郎, 金谷 泰宏, 伊藤 陽一, 松岡 健, 片山 隆行, 上杉 春雄, 佐光 一也, 武井 麻子, 下濱 俊, 佐藤 典宏, 菊地 誠志, 佐々木 秀直, 臨床神経学, 57, 12, 813, 813, 2017年12月
(一社)日本神経学会, 日本語

pStage III結腸癌に対するFOLFOXの第II相試験[NORTH/HGCSG1003]原発部位による解析　　　　　　　　　　　　　　　
篠原 敏樹, 結城 敏志, 川本 泰之, 中積 宏之, 高橋 典彦, 七戸 俊明, 久須美 貴哉, 中村 文隆, 小林 良充, 岩永 一郎, 伊藤 陽一, 坂本 直哉, 武冨 紹信, 平野 聡, 小松 嘉人, 日本癌治療学会学術集会抄録集, 55回, O29, 2, 2017年10月
(一社)日本癌治療学会, 日本語

North Japan multicenter phase II study of FOLFOX as adjuvant chemotherapy for stage III colon cancer (NORTH/HGCSG1003): Analysis of tumor location
A. Ishiguro, S. Yuki, Y. Kawamoto, H. Nakatsumi, N. Takahashi, T. Shichinohe, T. Kusumi, I. Iwanaga, T. Miyagishima, K. Hatanaka, K. Oomori, M. Nakamura, N. Senmaru, K. Iwai, M. Koike, N. Sakamoto, A. Taketomi, S. Hirano, Y. M. Ito, Y. Komatsu, ANNALS OF ONCOLOGY, 28, 2017年09月
OXFORD UNIV PRESS, 英語, 研究発表ペーパー・要旨（国際会議）

Stage III結腸癌の術後補助化学療法としてのFOLFOX療法の第II相臨床試験 NORTH/HGCSG1003　　　　　　　　　　　　　　　
仙丸 直人, 結城 敏志, 七戸 俊明, 高橋 典彦, 川本 泰之, 中積 宏之, 久須美 貴哉, 中村 文隆, 小林 良充, 岩永 一郎, 畑中 一映, 三澤 一仁, 岩井 和浩, 小池 雅彦, 伊藤 陽一, 坂本 直哉, 平野 聡, 武冨 紹信, 坂田 優, 小松 嘉人, 日本消化器病学会雑誌, 114, 臨増大会, A842, A842, 2017年09月
(一財)日本消化器病学会, 日本語

腹腔鏡下鼠径ヘルニア修復術の新しいトレーニングシステムの開発及び教育効果の検討 多施設無作為比較試験　　　　　　　　　　　　　　　
Poudel Saseem, 倉島 庸, 田中 公貴, 川瀬 寛, 村上 康洋, 川原田 陽, 伊藤 陽一, 七戸 俊明, 平野 聡, 日本外科学会定期学術集会抄録集, 117回, SF, 51, 2017年04月
(一社)日本外科学会, 日本語

MOLECULAR DETERMINANTS OF FUNCTIONAL CHANGES AND FIBROSIS DETERMINED BY NOVEL AUTOMATED OSCILLOMETRIC APPROACH TO MEASURE BRACHIAL ARTERY VASCULAR VOLUME ELASTIC MODULUS IN CHRONIC KIDNEY DISEASE
Keiichiro Yoshinaga, Yoichi Ito, Satoshi Fujii, Saori Nishio, Noriki Ochi, Katoh Chietsugu, Mamiko Inoue, Mutsumi Nishida, Osamu Manabe, Nagara Tamaki, JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 69, 11, 2086, 2086, 2017年03月
ELSEVIER SCIENCE INC, 英語, 研究発表ペーパー・要旨（国際会議）

North Japan multicenter phase II study of oxaliplatin-containing regimen as adjuvant chemotherapy for stage III colon cancer (NORTH/HGCSG1003).
Toshiaki Shichinohe, Satoshi Yuki, Norihiko Takahashi, Hiroshi Nakatsumi, Yasuyuki Kawamoto, Takaya Kusumi, Atsushi Ishiguro, Susumu Sogabe, Ichiro Iwanaga, Kazuteru Hatanaka, Kazuyoshi Oomori, Michio Nakamura, Naoto Senmaru, Kazuhiro Iwai, Masahiko Koike, Naoya Sakamoto, Akinobu Taketomi, Satoshi Hirano, Yoichi M. Ito, Yoshito Komatsu, JOURNAL OF CLINICAL ONCOLOGY, 35, 4, 2017年02月
AMER SOC CLINICAL ONCOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

左室収縮が保持された心不全における¹¹C-HED PETを用いた局所心筋交感神経分布の検討
相川忠夫, 納谷昌直, 小原雅彦, 真鍋徳子, 真鍋治, 小梁川和宏, 孫田恵一, 伊藤陽一, 志賀哲, 加藤千恵次, 玉木長良, 核医学(Web), 54, Supplement, 2017年

北海道における多系統萎縮症レジストリ研究 HoRC-MSA　　　　　　　　　　　　　　　
松島 理明, 佐久嶋 研, 矢部 一郎, 伊藤 陽一, 片山 隆行, 佐光 一也, 森 満, 下濱 俊, 佐藤 典宏, 菊地 誠志, 佐々木 秀直, 北海道保健福祉部健康安全局地域保健課感染症, 特定疾患グループ, 臨床神経学, 56, Suppl., S484, S484, 2016年12月
(一社)日本神経学会, 日本語

脊髄小脳変性症における歩行解析(第二報)　　　　　　　　　　　　　　　
白井 慎一, 矢部 一郎, 松島 理明, 伊藤 陽一, 米山 満, 佐々木 秀直, 臨床神経学, 56, Suppl., S487, S487, 2016年12月
(一社)日本神経学会, 日本語

北海道における多系統萎縮症のレジストリ研究 HoRC-MSA 2015-2016　　　　　　　　　　　　　　　
松島 理明, 佐久嶋 研, 矢部 一郎, 金谷 泰宏, 伊藤 陽一, 片山 隆行, 佐光 一也, 武井 麻子, 森 満, 下濱 俊, 佐藤 典宏, 菊地 誠志, 佐々木 秀直, 北海道保健福祉部健康安全局地域保健課感染症, 特定疾患グループ, 臨床神経学, 56, 11, 802, 802, 2016年11月
(一社)日本神経学会, 日本語

女性医療人の労働生活の質評価尺度の開発と検証
武冨 貴久子, 伊藤 陽一, 徳永 えり子, 平野 裕子, 藤野 ユリ子, 樗木 晶子, 大滝 純司, 医学教育, 47, Suppl., 190, 190, 2016年07月
(一社)日本医学教育学会, 日本語

An Evaluation Method of Lifetime Attributable Risk for Comparing Between Proton Beam Therapy and Intensity Modulated X-Ray Therapy for Pediatric Cancer Patients by Averaging Four Dose-Response Models for Carcinoma Induction
M. Tamura, Y. Ito, H. Sakurai, M. Mizumoto, S. Kamizawa, S. Murayama, H. Yamashita, S. Takao, R. Suzuki, H. Shirato, MEDICAL PHYSICS, 43, 6, 3508, 3508, 2016年06月
WILEY, 英語, 研究発表ペーパー・要旨（国際会議）

北海道における多系統萎縮症のレジストリ研究:HoRC-MSA 2015-2016
松島理明, 佐久嶋研, 矢部一郎, 金谷泰宏, 伊藤陽一, 片山隆行, 佐光一也, 武井麻子, 森満, 下濱俊, 佐藤典宏, 菊地誠志, 佐々木秀直, 臨床神経学(Web), 56, 11, 2016年

Ten Years' Mortality Data Of Patients With Chronic Obstructive Pulmonary Disease From The Hokkaido COPD Cohort Study
H. Makita, M. Suzuki, S. Konno, K. Shimizu, Y. M. Ito, M. Nishimura, AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 193, 2016年
AMER THORACIC SOC, 英語, 研究発表ペーパー・要旨（国際会議）

Safety analysis of FOLFOX as adjuvant chemotherapy for stage III colon cancer in phase II study (NORTH/HGCSG1003) - an analysis of surgeons vs oncologists
A. Ishiguro, S. Yuki, Y. Kawamoto, F. Nakamura, N. Takahashi, T. Shichinohe, T. Kusumi, S. Sogabe, K. Hatanaka, K. Misawa, M. Nenohi, H. Hayashi, H. Fukushima, M. Takahashi, T. Amano, Y. M. Ito, N. Sakamoto, A. Taketomi, S. Hirano, Y. Komatsu, ANNALS OF ONCOLOGY, 26, 50, 50, 2015年12月
OXFORD UNIV PRESS, 英語, 研究発表ペーパー・要旨（国際会議）

北海道における多系統萎縮症のレジストリ研究:HoRC‐MSA step 2
松島理明, 佐久嶋研, 矢部一郎, 伊藤陽一, 片山隆行, 佐光一也, 森満, 下濱俊, 佐藤典宏, 菊地誠志, 佐々木秀直, 臨床神経学(Web), 55, 12, 945(J‐STAGE), 945, 2015年12月
(一社)日本神経学会, 日本語

北海道における多系統萎縮症のレジストリ研究 HoRC-MSA step2　　　　　　　　　　　　　　　
松島 理明, 佐久嶋 研, 矢部 一郎, 伊藤 陽一, 片山 隆行, 佐光 一也, 森 満, 下濱 俊, 佐藤 典宏, 菊地 誠志, 佐々木 秀直, 臨床神経学, 55, 12, 945, 945, 2015年12月
(一社)日本神経学会, 日本語

Particle Therapy Using Protons or Carbon Ions for Cancer Patients With Cardiac Implantable Electronic Devices (CIEDs): A Retrospective Japan Radiological Society Multi-institutional Study
T. Hashimoto, Y. Demizu, T. Isobe, H. Numajiri, S. Fukuda, M. Wakatsuki, H. Yamashita, S. Murayama, S. Takamatsu, H. Katoh, K. Murata, R. Kohno, T. Arimura, T. Matsuura, Y. M. Ito, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 93, 3, E563, E564, 2015年11月
ELSEVIER SCIENCE INC, 英語, 研究発表ペーパー・要旨（国際会議）

NTCP Modeling Analysis of Acute Hematologic Toxicity in Whole-Pelvic Radiation Therapy for Gynecologic Malignancies: A Dosimetric Comparison of IMRT and Spot-Scanning Proton Therapy
T. Yoshimura, R. Kinoshita, S. Onodera, C. Toramatsu, R. Suzuki, Y. M. Ito, S. Takao, T. Matsuura, Y. Matsuzaki, S. Shimizu, K. Umegaki, H. Shirato, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 93, 3, E254, E254, 2015年11月
ELSEVIER SCIENCE INC, 英語, 研究発表ペーパー・要旨（国際会議）

Altered Vascular Elasticity Reflected Vascular Endothelial Dysfunction and Elevated Galectin-3 Using Novel Brachial Artery Vascular Volume Elastic Modulus With Automated Oscillometric Approach
Keiichiro Yoshinaga, Yuuki Tomiyama, Satoshi Fujii, Saori Nishio, Noriki Ochi, Chietsugu Katoh, Mamiko Inoue, Mutumi Nishida, Keisuke Takeuchi, Yoichi M. Ito, Nagara Tamaki, CIRCULATION, 132, 2015年11月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

The Voxel-based Analysis of FMISO-PET Image in Patients With Local Recurrence of Nasopharyngeal Carcinoma
Y. Nishikawa, K. Yasuda, S. Okamoto, Y. M. Ito, T. Mori, R. Onimaru, T. Shiga, K. Tsuchiya, S. Watanabe, W. Takeuchi, N. Katoh, Y. Kuge, N. Tamaki, H. Shirato, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 93, 3, E337, E337, 2015年11月
ELSEVIER SCIENCE INC, 英語, 研究発表ペーパー・要旨（国際会議）

HPV vaccination crisis in Japan (vol 385, pg 2571, 2015)
S. J. B. Hanley, E. Yoshioka, Y. Ito, R. Kishi, LANCET, 386, 9990, 248, 248, 2015年07月
ELSEVIER SCIENCE INC, 英語, その他

Safety analysis of FOLFOX as adjuvant chemotherapy for stage III colon cancer in phase II study (NORTH/HGCSG1003) - an analysis of surgeons vs oncologists
I. Iwanaga, S. Yuki, H. Fukushima, N. Takahashi, T. Shichinohe, T. Kusumi, F. Nakamura, S. Sogabe, K. Hatanaka, K. Oomori, K. Misawa, N. Senmaru, K. Iwai, T. Shinohara, M. Koike, K. Miyashita, T. Amano, Y. M. Ito, N. Sakamoto, A. Taketomi, S. Hirano, Y. Komatsu, ANNALS OF ONCOLOGY, 26, 2015年06月
OXFORD UNIV PRESS, 英語, 研究発表ペーパー・要旨（国際会議）

Safety analysis of FOLFOX as adjuvant chemotherapy for stage III colon cancer in phase II study (NORTH/HGCSG1003): Detailed analysis of peripheral sensory neuropathy.
Susumu Sogabe, Satoshi Yuki, Hiraku Fukushima, Norihiko Takahashi, Toshiaki Shichinohe, Takaya Kusumi, Fumitaka Nakamura, Ichiro Iwanaga, Kazuteru Hatanaka, Kencho Miyashita, Jun Konno, Kazuhito Uemura, Masaaki Nenohi, Masaya Kina, Naoya Sakamoto, Akinobu Taketomi, Satoshi Hirano, Toraji Amano, Yoichi M. Ito, Yoshito Komatsu, JOURNAL OF CLINICAL ONCOLOGY, 33, 3, 2015年01月
AMER SOC CLINICAL ONCOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

DIFFERENTIAL CHANGES OF COMPONENTS IN QUALITY OF LIFE OVER 5 YEARS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE PATIENTS
H. Makita, K. Nagai, M. Suzuki, K. Shimizu, S. Konno, Y. M. Ito, M. Nishimura, RESPIROLOGY, 19, 126, 126, 2014年11月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

Novel Simple and Accurate Quantitative Endothelial Function Measurements Using Brachial Artery Vascular Volume Elastic Modulus With Automated Oscillometric Approach
Keiichiro Yoshinaga, Yuuki Tomiyama, Satoshi Fujii, Saori Nishio, Naoko Matsuoka, Noriki Ochi, Chietsugu Katoh, Mamiko Inoue, Mutumi Nishida, Yoichi M. Ito, Hideo Nishibayashi, Nagara Tamaki, CIRCULATION, 130, 2014年11月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

Impaired coronary and peripheral artery vascular function in smokers - Comprehensive evaluation using Oxygen-15 labeled water PET and brachial artery ultrasound
Noriki Ochi, Keiichiro Yoshinaga, Yuuki Tomiyama, Chietsugu Katoh, Mamiko Inoue, Mutsumi Nishida, Eriko Suzuki, Osamu Manabe, Yoichi Ito, Nagara Tamaki, JOURNAL OF NUCLEAR MEDICINE, 55, 2014年05月
SOC NUCLEAR MEDICINE INC, 英語, 研究発表ペーパー・要旨（国際会議）

Predictive value of FDG PET at initial radioiodine therapy for survival of high-risk patients with differentiated thyroid cancer
Florian Gaertner, Shozo Okamoto, Tohru Shiga, Yoichi Ito, Yuko Uchiyama, Osamu Manabe, Naoya Hattori, Nagara Tamaki, JOURNAL OF NUCLEAR MEDICINE, 55, 2014年05月
SOC NUCLEAR MEDICINE INC, 英語, 研究発表ペーパー・要旨（国際会議）

Impaired Vascular Elastic Mechanics Predict Endothelial Dysfunction in Chronic Kidney Disease
YOSHINAGA Keiichiro, TOMIYAMA Yuuki, NISHIO Saori, MATSUOKA Naoko, OCHI Noriki, KATOH Chietsugu, INOUE Mamiko, ITO Yoichi, NISHIBAYASHI Hideo, FUJII Satoshi, TAMAKI Nagara, Circ J, 78, Supplement 1(CD-ROM), ROMBUNNO.PE-375, 2014年02月20日
英語

Impaired Peripheral Artery and Coronary Endothelial Function in Healthy Young Smokers Using Brachial Artery Ultrasound and Oxygen-15 Labeled Water PET
OCHI Noriki, YOSHINAGA Keiichiro, ITO Yoichi, TOMIYAMA Yuuki, KATOH Chietsugu, INOUE Mamiko, NISHIDA Mutsumi, SUZUKI Eriko, MANABE Osamu, TAMAKI Nagara, Circ J, 78, Supplement 1(CD-ROM), ROMBUNNO.OJ-039, 2014年02月20日
英語

SIMPLE PREDICTION OF RIGHT VENTRICULAR EJECTION FRACTION USING TRICUSPID ANNULAR PLANE SYSTOLIC EXCURSION IN PULMONARY HYPERTENSION
Takahiro Sato, Ichizo Tsujino, Noriko Oyama-Manabe, Hiroshi Ohira, Yoichi. M. Ito, Hiroyuki Sugimori, Asuka Yamada, Chisa Takashina, Taku Watanabe, Masaharu Nishimura, RESPIROLOGY, 18, 20, 20, 2013年11月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

Right Atrial Volume and Reservoir Function are Novel Predictors of Clinical Worsening in Pulmonary Hypertension
Takahiro Sato, Ichizo Tsujino, Hiroshi Ohira, Noriko Oyama-Manabe, Yoichi M. Ito, Masaharu Nishimura, CIRCULATION, 128, 22, 2013年11月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

THE EFFECTS OF AN ARG16GLY ADRB2 POLYMORPHISM ON RESPONSES TO SALMETEROL OR MONTELUKAST IN JAPANESE PATIENTS WITH MILD PERSISTENT ASTHMA
Satoshi Konno, Nobuyuki Hizawa, Hironi Makita, Kaoruko Shimizu, Tohru Sakamoto, Fumio Kokubu, Takefumi Saito, Takeo Endo, Hiroki Ninomiya, Hiroaki Iijima, Norihiro Kaneko, Yoichi Ito, Masaharu Nishimura, RESPIROLOGY, 18, 12, 12, 2013年11月
WILEY-BLACKWELL, 英語, 研究発表ペーパー・要旨（国際会議）

肺高血圧患者における右心室酸素代謝亢進は右心室容量の増加よりも肺血管抵抗の上昇と強く関連する
吉永恵一郎, 伊藤陽一, 大平洋, 辻野一三, 真鍋治, 加藤千恵次, 佐藤隆博, 真鍋徳子, 藤井聡, 西村正治, 玉木長良, 核医学, 50, 3, 214, 2013年09月30日
日本語

Gene scoring model to predict recurrence in low- and intermediate-risk uterine endometrial cancer: Establishment of uterine print
Tatsuyuki Chiyoda, Yoichi M. Ito, Fumio Kataoka, Wataru Yamagami, Hiroyuki Nomura, Hiroshi Tsuda, Hideo Tanaka, Masashi Takano, Sadako Nishimura, Yoko Iguchi, Shiho Hashimoto, Tomoko Yoshihama, Nobuyuki Susumu, Daisuke Aoki, JOURNAL OF CLINICAL ONCOLOGY, 31, 15, 2013年05月
AMER SOC CLINICAL ONCOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

有機フッ素化合物(11種類)の胎児期曝露による出生時体格への影響　　　　　　　　　　　　　　　
樫野 いく子, 佐々木 成子, 岡田 恵美子, 宮下 ちひろ, 山本 潤, 松浦 英幸, 伊藤 陽一, 松村 徹, 玉腰 暁子, 岸 玲子, 日本衛生学雑誌, 68, Suppl., S160, S160, 2013年03月
日本衛生学会, 日本語

有機フッ素化合物の胎児期曝露による1歳までのアレルギー症状との関連　　　　　　　　　　　　　　　
岡田 恵美子, 樫野 いく子, 佐々木 成子, 宮下 ちひろ, 山本 潤, 伊藤 陽一, 松浦 英幸, 松村 徹, 玉腰 暁子, 岸 玲子, 日本衛生学雑誌, 68, Suppl., S161, S161, 2013年03月
日本衛生学会, 日本語

Co-overexpression of GEP100 With EGFR Correlates With Early Recurrence After Breast Conservation Therapy (BCT)
R. Kinoshita, J. Nam, M. Hosoda, C. Kubota K, M. Tanino, A. Hashimoto, Y. M. Ito, S. Tanaka, H. Sabe, H. Shirato, INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, 84, 3, S227, S228, 2012年11月
ELSEVIER SCIENCE INC, 英語, 研究発表ペーパー・要旨（国際会議）

IMPROVING THE HEALTH OF JAPANESE WOMEN: ACCEPTANCE OF HPV VACCINATION IN MOTHERS OF ADOLESCENT GIRLS
S. Hanley, E. Yoshioka, Y. Ito, R. Konno, N. Sakuragi, R. Kishi, JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH, 65, A250, A251, 2011年08月
B M J PUBLISHING GROUP, 英語, 研究発表ペーパー・要旨（国際会議）

Annexin A5 is a potential biomarker for Alzheimer disease
Hitoshi Sohma, Mami Yamaguchi, Shin-ichi Imai, Kumiko Utsumi, Kyoichi Matsumoto, Hirohito Honda, Yuka Mizue, Masako Momma, Yoichi Ito, Yasuo Kokai, NEUROSCIENCE RESEARCH, 68, E66, E67, 2010年
ELSEVIER IRELAND LTD, 英語, 研究発表ペーパー・要旨（国際会議）

【原発不明がん】 Interface on Cancer Therapy 原発巣同定のアルゴリズム
倉橋 一成, 中川 和彦, 西尾 和人, 伊藤 陽一, 大橋 靖雄, がん分子標的治療, 7, 3, 160, 165, 2009年07月
がん治療を行うときに遺伝子情報を測定してサブグループを特定することで効率的な治療戦略をとることが、近年注目されている。治療が難しいとされている原発不明がんも、マイクロアレイによって遺伝子発現を測定することで遺伝子プロファイルが似ているがん種を同定し、そのがん種の治療を行うという戦略が計画されている。それに伴って、原発巣を同定するアルゴリズムを紹介する。(著者抄録), (株)メディカルレビュー社, 日本語

Prognostic factors of hepatocellular carcinoma with decompensated cirrhosis
Kazuhim Nouso, Yoichi M. Ito, Kenji Kuwaki, Shoji Uematsu, Kunflum Shiraga, Ryoichi Okamoto, Shinichiro Nakamura, Yoshiyuki Kobayashi, Yasuyuki Araki, Kohsaku Sakaguchi, Yasuo Ohashi, Kazuhide Yamamoto, GASTROENTEROLOGY, 134, 4, A365, A365, 2008年04月
W B SAUNDERS CO-ELSEVIER INC, 英語, 研究発表ペーパー・要旨（国際会議）

cDNAマクロアレイデータ解析における正規化手法の性能評価(<特集1>医薬品の有効性・安全性)
倉橋 一成, 伊藤 陽一, 松山 裕, 大橋 靖雄, 西尾 和人, 日本統計学会誌. シリーズJ, 36, 2, 147, 163, 2007年03月
一般社団法人日本統計学会, 日本語

Prognostic value of ABCF2 in ovarian clear cell adenocarcinoma.
H Tsuda, YM Ito, K Ito, S Nishimura, N Yaegashi, MJ Birrer, Y Ohashi, Y Hashiguchi, RS Berkowitz, SC Mok, JOURNAL OF CLINICAL ONCOLOGY, 23, 16, 463S, 463S, 2005年06月
AMER SOC CLINICAL ONCOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

ABCF2 is a new biomarker of ovarian clear cell adenocarcinoma.
S Nishimura, H Tsuda, YM Ito, K Ito, N Yaegashi, MJ Birrer, Y Ohashi, Y Hashiguchi, WS Berkowitz, SC Mok, JOURNAL OF CLINICAL ONCOLOGY, 23, 16, 466S, 466S, 2005年06月
AMER SOC CLINICAL ONCOLOGY, 英語, 研究発表ペーパー・要旨（国際会議）

ファルネシールトランスフェレース阻害剤,R115777のトランスレーショナル・スタディ-臨床第I相試験における遺伝子発現プロファイル解析結果　　　　　　　　　　　　　　　
秋山 慶太, 中川 和彦, 山本 信之, 小宮 武文, 植島 久雄, 浅井 暁, 鶴谷 純司, 森山 あづさ, 児玉 圭司, 築山 正嗣, 米阪 仁雄, 宮崎 昌樹, 金田 裕靖, 倉田 宝保, 田村 研治, 西尾 和人, 大橋 靖雄, 伊藤 陽一, W David, 伊藤 博夫, 小林 豪太, 福岡 正博, 日本呼吸器学会雑誌, 41, 増刊, 81, 81, 2003年03月
(一社)日本呼吸器学会, 日本語

A-5 分子標的薬剤に対する用量反応性遺伝子の探索(ゲノム・遺伝解析)(2003年度統計関連学会連合大会記録(日本統計学会第71回大会))
伊藤 陽一, 大橋 靖雄, 日本統計学会誌, 33, 3, 414, 414, 2003年
日本統計学会, 日本語

Low dose dobutamine stress gated Tc-99m-tetrofosmin SPECT provides additional value for identification of myocardial viability - Comparison with stress-rest perfusion SPECT and F-18-FDG PET.
K Yoshinaga, C Katoh, K Noriyasu, S Yamada, Y Ito, Y Kuge, T Kohya, A Kitabatake, N Tamaki, JOURNAL OF NUCLEAR MEDICINE, 43, 5, 93P, 94P, 2002年05月
SOC NUCLEAR MEDICINE INC, 英語, 研究発表ペーパー・要旨（国際会議）

Quantitative assessment of myocardial blood flow and flow reserve with (99m)-Tc-MIBI: Comparison with the results of measured by O-15-water PET.
Y Ito, K Noriyasu, H Furuyama, Y Iwado, K Yoshinaga, C Katoh, M Mabuchi, Y Kuge, T Kohya, A Kitabatake, N Tamaki, JOURNAL OF NUCLEAR MEDICINE, 43, 5, 187P, 187P, 2002年05月
SOC NUCLEAR MEDICINE INC, 英語, 研究発表ペーパー・要旨（国際会議）

Diminished endthelium-dependent coronary artery vasodilator function in smokers in healthy young adults evaluated by O-15-labeled water positron emission tomography.
Y Iwado, K Yoshinaga, H Furuyama, Y Ito, K Noriyasu, C Katoh, Y Kuge, E Tsukamoto, N Tamaki, JOURNAL OF NUCLEAR MEDICINE, 43, 5, 51P, 51P, 2002年05月
SOC NUCLEAR MEDICINE INC, 英語, 研究発表ペーパー・要旨（国際会議）

Greater reduction of coronary vasodilator function in the remote areas in patients with myocardial infarction than those without infarction.
K Yoshinaga, C Katoh, K Noriyasu, H Furuyama, Y Ito, Y Kuge, T Kohya, A Kitabatake, N Tamaki, JOURNAL OF NUCLEAR MEDICINE, 43, 5, 52P, 52P, 2002年05月
SOC NUCLEAR MEDICINE INC, 英語, 研究発表ペーパー・要旨（国際会議）

Evaluation of myocardial flow reserve and endothelial function late after Kawasaki disease with O-15-water PET.
H Furuyama, Y Odagawa, C Katoh, Y Iwado, K Yoshinaga, Y Ito, K Noriyasu, M Mabuchi, Y Kuge, K Kobayashi, N Tamaki, JOURNAL OF NUCLEAR MEDICINE, 43, 5, 344P, 344P, 2002年05月
SOC NUCLEAR MEDICINE INC, 英語, 研究発表ペーパー・要旨（国際会議）

Decreased myocardial oxygen consumption and cardiac efficiency in dilated cardiomyopathy assessed by positron emission tomography with C-11 acetate.
K Noriyasu, K Yoshinaga, Y Ito, C Katoh, H Furuyama, Y Iwado, M Mabuchi, Y Kuge, T Kohya, A Kitabatake, N Tamaki, JOURNAL OF NUCLEAR MEDICINE, 43, 5, 189P, 189P, 2002年05月
SOC NUCLEAR MEDICINE INC, 英語, 研究発表ペーパー・要旨（国際会議）

Reduced coronary flow reserve and endothelial function after Kawasaki disease using O-15-water PET
H Furuyama, Y Odagawa, C Katoh, Y Iwado, K Yoshinaga, Y Ito, K Noriyasu, Y Kuge, N Tamaki, K Kobayashi, CIRCULATION, 104, 17, 515, 515, 2001年10月
LIPPINCOTT WILLIAMS & WILKINS, 英語, 研究発表ペーパー・要旨（国際会議）

Regional differences in optimal threshold for viability assessment by FDG-SPECT.
M Mabuchi, K Yoshinaga, K Morita, K Noriyasu, Y Ito, H Furuyama, Y Iwado, N Kubo, C Katoh, Y Kuge, N Tamaki, JOURNAL OF NUCLEAR MEDICINE, 42, 5, 180P, 180P, 2001年05月
SOC NUCLEAR MEDICINE INC, 英語, 研究発表ペーパー・要旨（国際会議）

Reduced coronary flow reserve in well controlled hypercholesterolemic patients without perfusion abnormality or coronary stenosis.
K Yoshinaga, C Katoh, K Noriyasu, H Furuyama, M Mabuchi, Y Iwado, Y Ito, Y Kuge, T Kohya, A Kitabatake, N Tamaki, JOURNAL OF NUCLEAR MEDICINE, 42, 5, 90P, 91P, 2001年05月
SOC NUCLEAR MEDICINE INC, 英語, 研究発表ペーパー・要旨（国際会議）

Quantitative analysis for myocardial glucose utilization ln patients with LV dysfunction by FDG dynamic positron tomography.
K Morita, K Yoshinaga, M Mabuchi, Y Ito, K Noriyasu, Y Kuge, C Katoh, T Kohya, A Kitabatake, N Tamaki, JOURNAL OF NUCLEAR MEDICINE, 42, 5, 53P, 53P, 2001年05月
SOC NUCLEAR MEDICINE INC, 英語, 研究発表ペーパー・要旨（国際会議）

Reduction of coronary flow reserve in the area with and without ischemia on stress perfusion spect in patients with coronary artery disease.
K Yoshinaga, C Katoh, K Noriyasu, H Furuyama, M Mabuchi, Y Iwado, Y Ito, Y Kuge, T Kohya, A Kitabatake, N Tamaki, JOURNAL OF NUCLEAR MEDICINE, 42, 5, 179P, 179P, 2001年05月
SOC NUCLEAR MEDICINE INC, 英語, 研究発表ペーパー・要旨（国際会議）

Transient LV dysfunction in ischemic myocardium due to post-exercise stunning not subendocardial hypoperfusion. Comparative study with exercise and pharmacological stress gated myocardial SPECT.
H Furuyama, Y Iwado, K Yoshinaga, M Mabuchi, Y Ito, K Noriyasu, N Tamaki, JOURNAL OF NUCLEAR MEDICINE, 42, 5, 179P, 179P, 2001年05月
SOC NUCLEAR MEDICINE INC, 英語, 研究発表ペーパー・要旨（国際会議）

観察研究データの統計解析-傾向スコアの活用-　　　　　　　　　　　　　　　
伊藤 陽一, 統計数理研究所
日本医師会ORCA管理機構シンポジウム, 2019年02月12日, 日本語, 口頭発表（招待・特別）
東京 日本, ［国内会議］

データベースの構築や観察研究をどのように進めていけばいいか　　　　　　　　　　　　　　　
伊藤 陽一, 統計数理研究所
高知大学臨床試験セミナー, 2019年01月22日, 日本語, 口頭発表（招待・特別）
高知 日本, ［国内会議］

JMP Proで混合効果モデルを使いこなそう　　　　　　　　　　　　　　　
伊藤 陽一, 統計数理研究所
Discovery Summit Japan 2018, 2018年11月16日, 日本語, 口頭発表（招待・特別）
東京 日本, ［国内会議］

医薬品評価における医学統計学の役割　　　　　　　　　　　　　　　
伊藤 陽一, 統計数理研究所
統計思考力育成事業 統計数理研究所 公開講演会 創薬のフロンティア データサイエンスの挑戦, 2018年11月01日, 日本語, 口頭発表（招待・特別）
立川 日本, ［国際会議］

医療分野のデータサイエンティスト：生物統計家ってどんな仕事　　　　　　　　　　　　　　　
伊藤 陽一, 統計数理研究所
一般社団法人データサイエンティスト協会シンポジウム, 2018年10月19日, 日本語, 口頭発表（招待・特別）
東京 日本, ［国内会議］

臨床研究におけるリアルワールドデータの統計解析　　　　　　　　　　　　　　　
伊藤 陽一, 統計数理研究所
第17回久留米大学バイオ統計フォーラム, 2018年10月05日, 日本語, 口頭発表（招待・特別）
福岡 日本, ［国内会議］

臨床試験におけるEstimandの考え方　　　　　　　　　　　　　　　
伊藤 陽一, 統計数理研究所
第7回DIA医薬品開発に携わる生物統計専門家でない方のための統計ワークショップ, 2018年09月03日, 日本語, 口頭発表（一般）
東京 日本, ［国内会議］

M&S概論　　　　　　　　　　　　　　　
伊藤 陽一, 統計数理研究所
医薬品開発のためのPPK・PD研究会 2018年セミナー M&Sコース, 2018年08月23日, 日本語, 口頭発表（一般）
横浜 日本, ［国内会議］

臨床研究における統計手法の高度化と医療健康データ科学研究センターの取り組み　　　　　　　　　　　　　　　
伊藤 陽一, 統計数理研究所
医療イノベーション推進センター研修会, 2018年06月26日, 日本語, 口頭発表（招待・特別）
神戸 日本, ［国内会議］

膀胱がんサバイバーの術前意思決定サポートツールの開発
科学研究費助成事業
2022年04月01日 - 2025年03月31日
丸山 覚, 伊藤 陽一, 大澤 崇宏, 小笠原 克彦
日本学術振興会, 基盤研究(C), 北海道大学, 22K09516

尿中エクソソーム内のmRNAに基づく新たな膀胱がん診断法の開発
科学研究費助成事業
2022年04月01日 - 2025年03月31日
大澤 崇宏, 伊藤 陽一, 安部 崇重, 樋田 京子, 篠原 信雄
日本学術振興会, 基盤研究(C), 北海道大学, 22K09439

抗がん剤治療における産業・医療・保険に関するパレート効率性に関する実証研究
科学研究費助成事業 挑戦的研究(萌芽)
2020年07月 - 2022年03月
児玉 耕太, 仙石 愼太郎, 伊藤 陽一, 城野 博史
査読付き論文としての成果として、各癌種別の臨床試験結果から予測した治療の費用対効果の解析（メゾ）に関して、Sustainability[2020, IF: 3.251]3報, JPM[2021, IF:4.945]、医療機関での抗がん剤治療の治療技術別の治療前治療後労働生産性の比較（ミクロ）に関して、Drug Discovery Today[2020, IF:7.321], Cancers[2021, IF:6.639]の報告を行った。
日本学術振興会, 挑戦的研究(萌芽), 立命館大学, 研究分担者, 競争的資金, 20K20769

膀胱がんサバイバーの患者立脚型アウトカムを適切に測定できるQOL評価法の確立　　　　　　　　　　　　　　　
科研費基盤研究(C)
2018年04月 - 2021年03月
大澤 崇宏
競争的資金

研究データの質向上の指導者育成プログラム開発事業(各論2 品質管理編)　　　　　　　　　　　　　　　
研究データの質向上の指導者育成プログラム開発事業
2018年04月 - 2020年03月
岩田 洋, 順天堂大学医学部大学院循環器内科
競争的資金

欠測を伴うコホートに対するケース・コホートデザインの適用と解析方法の開発
科学研究費助成事業
2013年04月01日 - 2017年03月31日
和泉 志津恵, 竹内 文乃, 末永 聡史, 永田 大貴, 玉腰 暁子, 伊藤 陽一, 野間 久史
ケース・コホート研究では，コホート全体ではなく一部の選択された対象者のみから高価なゲノム情報を測定することにより，研究のコスト・労力が大幅に節減できる。しかし，対象者から観測されるデータには頻繁に欠測値が含まれるため，データ解析に困難を伴う。本研究では，欠測を伴うコホートデータに対応した，ケース・コホート研究の新規な理論的枠組みを開発した。そして，大規模なゲノム疫学研究への提案方法の応用を検討した。数値実験により検証した結果から，コホート内の大部分の対象者のアウトカムが欠測となる場合に，既存の方法でサブコホートの抽出やデータ解析を行うと，興味ある変数の効果にバイアスが生じることが示唆された。
日本学術振興会, 基盤研究(C), 25330039

非小細胞肺癌に対する定位放射線治療後の放射線肺臓炎発症に関与する遺伝子多型の研究
科学研究費助成事業
2012年04月01日 - 2016年03月31日
大西 洋, 塩山 善之, 吉武 忠正, 伊藤 陽一, 白土 博樹, 今井 高志, 鬼丸 力也, 小久保 雅樹, 栗山 健吾, 小宮山 貴史, 冨永 理人, 大栗 実彦, 野中 穂高, 青木 真一, 松本 康男, 松下 晴雄, 高山 賢二, 井上 哲也, 加藤 徳雄, 山下 英臣, 唐澤 克之, 江原 威, 植木 奈美, 松尾 幸憲
早期の非小細胞肺癌に対する定位放射線治療は、高い有効性と安全性から期待の大きい治療法である。重症の放射線肺炎のリスク因子の一つとして肺線維症が挙げられているが、詳細は明らかにされていない。そこで、放射線肺炎との関連が報告されているTGFb1遺伝子上または周辺の多型および、炎症関連遺伝子多型が定位放射線治療後の肺臓炎発症リスクと関連するか検証した。その結果、肺炎症状（CTCEA grade2以上）についてはステロイド使用歴、平均肺線量、遺伝子多型：rs1801270,rs1800470が、CT上の肺炎所見（照射体積外に発生）についてはステロイドの使用歴と遺伝子多型rs1800470が挙げられた。
日本学術振興会, 基盤研究(C), 山梨大学, 24591837

臨床試験関連業種における統計的品質管理手法の導入に関する研究　　　　　　　　　　　　　　　
若手研究(B)
2010年04月 - 2013年03月
伊藤 陽一
科学研究費補助金, 研究代表者, 競争的資金

循環器疾患のマルチモダリティ画像診断統合化データベースを用いた最適診断樹の研究
科学研究費助成事業
2011年 - 2013年
真鍋 徳子, 玉木 長良, 吉永 恵一郎, 伊藤 陽一, 遠藤 晃
循環器疾患における医療費削減及び診療の質的向上を目指し、増加する冠動脈CTの読影業務を効率化し、かつ、研究用データベースとして活用できる冠動脈CT読影支援システムを開発した。開発したシステムは、各種CT再構成画像を血管ごとに自動分類することで画像選択を省力化し、更に画像上の病変位置や狭窄度、プラーク性状等の病変情報を管理して過去との病変比較を容易にすることを特徴とする。虚血性心疾患を対象に、本システムの臨床評価を行ったところ、従来のPACS等を用いたレポート入力による読影法と比較して、読影時間が減少、また熟練読影医と若手読影医の病変部位の一致率が向上し、本システムの有効性が示された。
日本学術振興会, 基盤研究(C), 北海道大学, 23591743