基本情報

所属

• 医学研究院　社会医学系部門　社会医学分野

職名

• 准教授

学位

• 博士（保健学）（2015年03月 東京大学）
• 公衆衛生学修士（専門職）（2012年03月 東京大学）

ホームページURL

https://biostat-hokudai.jp

ORCID ID

•  https://orcid.org/0000-0001-6254-2225

J-Global ID

• 201801009279443751

研究キーワード

• 臨床研究   疫学   臨床試験   生物統計学   

研究分野

• ライフサイエンス / 衛生学、公衆衛生学分野：実験系を含まない
• ライフサイエンス / 医療管理学、医療系社会学
• 情報通信 / 統計科学

担当教育組織

•  学士課程　医学部（医学科）
•  修士課程　医学院
•  博士課程　医学院

職歴

• 2018年12月 - 現在 京都府立医科大学 生物統計学 客員講師
• 2018年10月 - 現在 北海道大学 大学院医学研究院 医学統計学 准教授
• 2022年08月 - 2023年03月 コペンハーゲン大学 生物統計学部門 客員研究員
• 2022年04月 - 2022年09月 京都大学 大学院医学研究科 講師（非常勤）
• 2021年04月 - 2021年06月 京都大学 大学院医学研究科 講師（非常勤）
• 2018年04月 - 2019年03月 京都大学 大学院医学研究科 講師（非常勤）
• 2018年08月 - 2018年09月 京都府立医科大学 大学院医学研究科 生物統計学 講師（学内）
• 2018年04月 - 2018年09月 武庫川女子大学 非常勤講師
• 2015年04月 - 2018年07月 京都府立医科大学 大学院医学研究科 生物統計学 助教
• 2017年04月 - 2017年09月 武庫川女子大学 非常勤講師

学歴

• 2012年04月 - 2015年03月   東京大学大学院   医学系研究科   健康科学・看護学専攻 博士後期課程
• 2010年04月 - 2012年03月   東京大学大学院   医学系研究科   公共健康医学専攻 専門職修士課程
• 2006年04月 - 2010年03月   東京大学   医学部   健康科学・看護学科

所属学協会

• 日本臨床試験学会   日本計算機統計学会   日本分類学会   ENAR   International Society of Clinical Biostatistics   日本計量生物学会   

研究活動情報

論文

• Weight loss and functional decline in older Japanese people: A cohort study using large-scale claims data

  Sachiko Ono, Yusuke Sasabuchi, Hayato Yamana, Isao Yokota, Akira Okada, Hiroki Matsui, Shunsuke Itai, Kazumichi Yonenaga, Kanata Tonosaki, Rinji Watanabe, Yosuke Ono, Hideo Yasunaga, Kazuto Hoshi

  Archives of Gerontology and Geriatrics 2024年05月 [査読有り]
  
• A nationwide phase II study of delayed local treatment for children with high-risk neuroblastoma: The Japan Children's Cancer Group Neuroblastoma Committee Trial JN-H-11.

  Akihiro Yoneda, Hiroyuki Shichino, Tomoro Hishiki, Kimikazu Matsumoto, Miki Ohira, Takehiko Kamijo, Tatsuo Kuroda, Toshinori Soejima, Atsuko Nakazawa, Tetsuya Takimoto, Isao Yokota, Satoshi Teramukai, Hideto Takahashi, Takashi Fukushima, Junichi Hara, Michio Kaneko, Hitoshi Ikeda, Tatsuro Tajiri, Hideo Mugishima, Akira Nakagawara

  Pediatric blood & cancer e30976  2024年04月05日 

  PURPOSE: Survival rates of patients with high-risk neuroblastoma are unacceptable. A time-intensified treatment strategy with delayed local treatment to control systemic diseases has been developed in Japan. We conducted a nationwide, prospective, single-arm clinical trial with delayed local treatment. This study evaluated the safety and efficacy of delayed surgery to increase treatment intensity. PATIENTS AND METHODS: Seventy-five patients with high-risk neuroblastoma were enrolled in this study between May 2011 and September 2015. Delayed local treatment consisted of five courses of induction chemotherapy (cisplatin, pirarubicin, vincristine, and cyclophosphamide) and myeloablative high-dose chemotherapy (melphalan, etoposide, and carboplatin), followed by local tumor extirpation with surgery and irradiation. The primary endpoint was progression-free survival (PFS). The secondary endpoints were overall survival (OS), response rate, adverse events, and surgical complications. RESULTS: Seventy-five patients were enrolled, and 64 were evaluable (stage 3, n = 8; stage 4, n = 56). The estimated 3-year PFS and OS rates (95% confidence interval [CI]) were 44.4% [31.8%-56.3%] and 80.7% [68.5%-88.5%], resspectively. The response rate of INRC after completion of the treatment protocol was 66% (42/64; 95% CI: 53%-77%; 23 CR [complete response], 10 VGPR [very good partial response], and nine PR [partial response]). None of the patients died during the protocol treatment or within 30 days of completion. Grade 4 adverse effects, excluding hematological adverse effects, occurred in 48% of patients [31/64; 95% CI: 36%-61%]. Major Surgical complications were observed in 25% of patients [13/51; 95% CI: 14%-40%]. CONCLUSION: This study indicates that delayed local treatment is feasible and shows promising efficacy, suggesting that this treatment should be considered further in a comparative study of high-risk neuroblastoma.
• Exploring the influence of a financial incentive scheme on early mobilization and rehabilitation in ICU patients: an interrupted time-series analysis

  Yoko Unoki, Sachiko Ono, Yusuke Sasabuchi, Yohei Hashimoto, Hideo Yasunaga, Isao Yokota

  BMC Health Services Research 24 1 2024年02月24日 

  Abstract Background Clinical guidelines recommend early mobilization and rehabilitation (EMR) for patients who are critically ill. However, various barriers impede its implementation in real-world clinical settings. In 2018, the Japanese universal healthcare coverage system announced a unique financial incentive scheme to facilitate EMR for patients in intensive care units (ICU). This study evaluated whether such an incentive improved patients’ activities of daily living (ADL) and reduced their hospital length of stay (LOS). Methods Using the national inpatient database in Japan, we identified patients admitted to the ICU, who stayed over 48 hours between April 2017 and March 2019. The financial incentive required medical institutions to form a multidisciplinary team approach for EMR, development and periodic review of the standardized rehabilitation protocol, starting rehabilitation within 2 days of ICU admission. The incentive amounted to 34.6 United States Dollars per patient per day with limit 14 days, structured as a per diem payment. Hospitals were not mandated to provide detailed information on individual rehabilitation for government, and the insurer made payments directly to the hospitals based on their claims. Exposure was the introduction of the financial incentive defined as the first day of claim by each hospital. We conducted an interrupted time-series analysis to assess the impact of the financial incentive scheme. Multivariable radon-effects regression and Tobit regression analysis were performed with random intercept for the hospital of admission. Results A total of 33,568 patients were deemed eligible. We confirmed that the basic assumption of ITS was fulfilled. The financial incentive was associated with an improvement in the Barthel index at discharge (0.44 points change in trend per month; 95% confidence interval = 0.20–0.68) and shorter hospital LOS (− 0.66 days change in trend per month; 95% confidence interval = − 0.88 – -0.44). The sensitivity and subgroup analyses showed consistent results. Conclusions The study suggests a potential association between the financial incentive for EMR in ICU patients and improved outcomes. This incentive scheme may provide a unique solution to EMR barrier in practice, however, caution is warranted in interpreting these findings due to recent changes in ICU care practices.
• Longitudinal mortality risks and kidney functional outcomes in Japanese living kidney donors.

  Takayuki Hirose, Kiyohiko Hotta, Takahiro Osawa, Isao Yokota, Tasuku Inao, Tatsu Tanabe, Naoya Iwahara, Nobuo Shinohara

  International journal of urology : official journal of the Japanese Urological Association 2024年01月19日 

  OBJECTIVES: Previous studies suggested that living kidney donors do not have a higher risk of death or kidney failure than the general population. However, living kidney donor risk is controversial. Furthermore, only a few studies have evaluated long-term kidney function after kidney donation. METHODS: This study evaluated Japanese kidney donor' long-term outcomes, including mortality and kidney function. From 1965 to 2015, 230 donors (76 males, 154 females, and a median age of 54) were enrolled in this study. The median observation period was 11.0 (range, 0.3-41.0) years. RESULTS: In total, 215 donors were still alive, and 15 had died. Causes of death included malignancies, cardiovascular disease, pneumonia, suicide, gastrointestinal bleeding, and kidney failure. Actual donor survival rates at 10, 20, and 30 years were 95.3%, 90.7%, and 80.9%, respectively. These values were comparable to age- and gender-matched expected survival. Long-term kidney function after donation was evaluated in 211 donors with serum creatinine data. Two donors developed kidney failure 24 and 26 years post-donation, respectively. The percentage of donors whose estimated glomerular filtration rate (eGFR) remained ≥45 mL/min/1.73 m2 at 10, 20, and 30 years after donation were 84.2%, 73.0%, and 63.9%, respectively. Survival rates of donors with eGFR <45 mL/min/1.73 m2 were comparable to those in persons with eGFR >45 mL/min/1.73 m2 . CONCLUSION: Our findings revealed that kidney donors did not have a higher long-term risk of death than the general population. Although some donors showed decreased kidney function after donation, kidney function did not impact their survival.
• Decoupling power and type I error rate considerations when incorporating historical control data using a test‐then‐pool approach

  Kazufumi Okada, Shiro Tanaka, Jun Matsubayashi, Keita Takahashi, Isao Yokota

  Biometrical Journal 2024年01月
• Posttransplant cyclophosphamide in unrelated and related peripheral blood stem cell transplantation from HLA-matched and 1 allele mismatched donor.

  Junichi Sugita, Takashi Kuroha, Jun Ishikawa, Tetsuya Eto, Kentaro Fukushima, Isao Yokota, Koichi Akashi, Shuichi Taniguchi, Mine Harada, Takanori Teshima

  Bone marrow transplantation 2023年12月19日 

  Posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis has been increasingly used in HLA-haploidentical transplantation and recent studies also demonstrated the efficacy of PTCy in HLA-matched transplantation. We conducted a prospective multicenter phase II study to evaluate the safety and efficacy of PTCy with tacrolimus and mycophenolate mofetil in 43 patients who underwent HLA-matched (n = 21), 1 allele mismatched (n = 20), or 2 allele mismatched (n = 2) peripheral blood stem cell transplantation (PBSCT) following myeloablative (n = 28) or reduced-intensity (n = 15) conditioning. The incidence of grade III-IV acute GVHD at 100 days was 2.3%. The incidences of grades II-IV acute GVHD, all grade chronic GVHD, and moderate to severe chronic GVHD at 2 years were 16.3%, 14.0%, and 4.7%, respectively. Overall survival, disease-free survival, and non-relapse mortality at 2 years were 75.3%, 74.0%, and 7.0%, respectively. GVHD-free, relapse-free survival at 2 years was 67.0%. The rate of off-immunosuppressants in patients who survived without relapse at 2 years was 85.4%. These results indicate that PTCy is a valid option for GVHD prophylaxis in both HLA-matched and HLA 1-2 allele mismatched PBSCT.
• Applicable predictive factors extracted from peak flow trajectory for the prediction of asthma exacerbation.

  Yichi Yang, Hirokazu Kimura, Isao Yokota, Hironi Makita, Michiko Takimoto-Sato, Machiko Matsumoto-Sasaki, Munehiro Matsumoto, Akira Oguma, Yuki Abe, Nozomu Takei, Houman Goudarzi, Kaoruko Shimizu, Masaru Suzuki, Masaharu Nishimura, Satoshi Konno

  Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology 2023年11月23日 

  BACKGROUND: Real-time asthma exacerbation prediction and acute asthma attack detection are essential for patients with severe asthma. Peak expiratory flow (PEF) exhibits a potential for use in long-term asthma self-monitoring. However, the method for processing PEF calculations remains to be clarified. OBJECTIVE: Present research was conducted to develop clinically applicable novel exacerbation predictors calculated using PEF records. METHODS: Previously proposed exacerbation predictors, including the slope of PEF, percentage predicted PEF, percentage best PEF, the highest PEF over the lowest PEF within specific periods, and PEF coefficient of variation, as well as a novel indicator delta PEF moving average (ΔMA), defined as the difference between 14-day and 3-day average PEF values along with MA adjusted for PEF reference (%ΔMA), were verified using the Hokkaido-based Investigative Cohort Analysis for Refractory Asthma data of 127 patients with severe asthma from whom 73,503 PEF observations were obtained. Receiver operating characteristic curves for all predictors were drawn and the corresponding areas under the curve (AUCs) were computed. Regression analysis for MA and % MA were conducted. RESULTS: The most outstanding performance was demonstrated by ΔMA and %ΔMA, with AUC values of 0.659 and 0.665 in the univariate model, respectively. When multivariate models incorporated with random intercepts for individual participants, the AUC for ΔMA and %ΔMA soared to 0.907 and 0.919, respectively. CONCLUSION: The MA and % MA are valuable indicators that should be considered when deriving predictors from the PEF trajectory for monitoring exacerbations in patients with severe asthma.
• Minimal Residual Disease Detected by the 7NB-mRNAs ddPCR Assay Is Associated with Disease Progression in High-Risk Neuroblastoma Patients: A Prospective Multicenter Observational Study in Japan.

  Noriyuki Nishimura, Toshiaki Ishida, Isao Yokota, Kimikazu Matsumoto, Hiroyuki Shichino, Hiroyuki Fujisaki, Takeo Sarashina, Takehiko Kamijo, Tetsuya Takimoto, Tomoko Iehara, Tatsuro Tajiri, On Behalf Of The Jccg Neuroblastoma Committee

  Biology 12 10 2023年10月20日 

  High-risk neuroblastoma (HR-NB) patients remain far from obtaining optimal outcomes, with more than 50% relapse/regrowth rate despite current intensive multimodal therapy. This originated from the activation/proliferation of chemoresistant minimal residual disease (MRD). MRD with a significant prognostic was reported by several quantitative PCR (qPCR) or droplet digital PCR (ddPCR) assays quantitating different sets of NB-associated mRNAs (NB-mRNAs). The 7NB-mRNAs ddPCR assay quantitating CRMP1, DBH, DDC, GAP43, ISL1, PHOX2B, and TH mRNAs was reported to outperform other qPCR assays by a retrospective in-house observational study. In the present study, the Japan Children's Cancer Group (JCCG) Neuroblastoma Committee conducted a prospective multicenter observational study aimed at evaluating a prognostic value of MRD in bone marrow (BM-MRD) and peripheral blood (PB-MRD) detected by 7NB-mRNAs ddPCR assay. Between August 2018 and August 2022, 7 HR-NB patients who registered for JCCG clinical trials (JN-H-11 and JN-H-15) were enrolled. A total of 19 BM and 19 PB samples were collected, and 4/15 BM and 4/15 PB samples were classified as progressive disease (PD)/non-PD samples. BM-MRD and PB-MRD estimated area under curve (AUC) of 0.767 and 0.800 with a significant accuracy (AUC > 0.7). The present study validated a prognostic value of BM-MRD obtained by a previous study (AUC 0.723) and revealed the significant accuracy of PB-MRD as well as BM-MRD.
• Prognostic Value of Hematogones in Patients With Hematopoietic Disorders After Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

  Hirotaka Mori, Daisuke Koyama, Yuki Sato, Yuki Kataoka, Shunsuke Taito, Takashi Ishio, Takanori Teshima, Isao Yokota

  Cureus 15 10 e47184  2023年10月 

  This systematic review and meta-analysis aimed to determine whether hematogones in patients with hematopoietic disorders after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are associated with clinical outcomes. We searched the MEDLINE, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform databases from their inception to March 2023. The primary outcome in the summary of findings was three-year relapse-free survival (RFS), and secondary outcomes in the summary of findings included three-year relapse, non-relapse mortality (NRM), overall survival (OS), acute and chronic graft-versus-host disease (GVHD), and infection. The certainty of evidence was determined using the grading of recommendation assessment, development, and evaluation approaches. A systematic review and meta-analysis of outcome measures were conducted using a random-effects model. This study protocol was registered in the Open Science Framework. A total of six studies (including 888 patients) were included in the meta-analysis. Hematogones were related to favorable three-year RFS (risk ratio (RR) = 1.84; 95% confidence interval (CI) = 1.01 to 3.34) and favorable NRM (RR = 0.14; 95% CI = 0.04 to 0.51), OS (RR = 1.51; 95% CI = 1.13 to 2.02), and acute GVHD (RR = 0.44; 95% CI = 0.33 to 0.59). The certainty of the evidence was low for RFS, NRM, OS, and acute GVHD. Evidence regarding the association between hematogones, relapse, and infections is uncertain. Hematogones may be a prognostic factor for long-term prognosis and acute adverse events in patients with hematopoietic disorders after allo-HSCT. Further studies are required to address the long-term life-threatening events.
• Posttransplant cyclophosphamide in HLA-matched and 1-2 allele mismatched peripheral blood stem cell transplantation

  Takanori Teshima, Junichi Sugita, Takashi Kuroha, Jun Ishikawa, Tetsuya Eto, Kentaro Fukushima, Isao Yokota, Koichi Akashi, Mine Harada, Shuichi Taniguchi

  2023年09月22日
• Factors associated with household transmission of SARS-CoV-2 omicron variant to health care workers: A retrospective cohort study.

  Keisuke Kagami, Reiko Oyamada, Tsubasa Watanabe, Sho Nakakubo, Takahiro Hayashi, Sumio Iwasaki, Tatsuya Fukumoto, Takayuki Usami, Kasumi Hayasaka, Shinichi Fujisawa, Chiaki Watanabe, Mutsumi Nishida, Takanori Teshima, Yusuke Niinuma, Isao Yokota, Yoh Takekuma, Mitsuru Sugawara, Nobuhisa Ishiguro

  International journal of nursing practice 29 5 e13195  2023年08月24日 

  AIM: The aim of this study was to determine the risk factors for household transmission of the omicron variant of SARS-CoV-2. BACKGROUND: The household infection rate has been reported to be higher for the omicron variant than for non-omicron variants of SARS-CoV-2. Determination of the risk factors for household transmission of the omicron variant is therefore important. DESIGN: A Retrospective Cohort Study was conducted. METHODS: When family members of health care workers (HCWs) were found to be infected with SARS-CoV-2, the HCWs had to receive two nucleic acid amplification tests for SARS-CoV-2: immediately after and 5 to 10 days after the onset of COVID-19 in the family members. Risk factors of household transmission were analysed by comparing cases (HCWs infected with SARS-CoV-2) and controls (HCWs not infected with SARS-CoV-2) using multivariable analysis. RESULTS: Unvaccinated status (OR: 3.97), age of index cases (≤6 years) (OR: 1.94) and staying at home with index cases (OR: 10.18) were risk factors for household transmission. CONCLUSION: If there is a strong desire to avoid household infection, family members infected with SARS-CoV-2 should live separately during the period of viral shedding.
• Impact of cancer on the prevalence, management, and outcome of patients with chronic thromboembolic pulmonary hypertension.

  Junichi Nakamura, Ichizo Tsujino, Hideki Shima, Toshitaka Nakaya, Ayako Sugimoto, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Masaru Suzuki, Isao Yokota, Satoshi Konno

  Journal of thrombosis and thrombolysis 2023年08月24日 

  INTRODUCTION: Chronic thromboembolic pulmonary hypertension (CTEPH) results from unresolved thrombotic obstruction of the pulmonary vasculature. Cancer is a known risk factor for CTEPH. This study aimed to determine the impact of cancer on the prevalence, management, and outcomes of patients with CTEPH. MATERIALS AND METHODS: In this retrospective study involving 99 patients sequentially diagnosed with CTEPH in our hospital, the prevalence of 10 comorbid conditions including a past history of cancer at the time of CTEPH diagnosis were calculated. RESULTS: Among the 99 patients, 17 (17%) had a history of cancer. Breast cancer (n = 6) was the most common cancer type, followed by gastrointestinal cancer (n = 3), uterine cancer (n = 2), and malignant lymphoma (n = 2). Between patients with and without cancer, there were no differences in the demographics, severity of CTEPH, and management; however, the 5-year survival rate was lower for patients with cancer (65%) than for those without (89%). In addition, patients with cancer had significantly worse survival than those without (p = 0.03 by log-rank test). During follow-up, nine patients developed cancer after the diagnosis of CTEPH. Among the 99 patients, 13 died during follow-up, 6 (46%) of whom died of cancer. CONCLUSIONS: 17% of our patients with CETPH were diagnosed with cancer, with breast and gastrointestinal tract cancers being the most common. Cancer comorbidity was associated with a poor prognosis and contributed to death in 46% of deceased patients. The impact of cancer on CTEPH should be further evaluated in the future.
• The risk of weekend biopsy: Impact of specimen source and fixation status on HER2 assessment in the treatment of advanced gastric cancer (The HER_WEEKEND study).

  Michio Nakamura, Ayako Watanabe, Aki Yoshizawa, Sari Iwasaki, Asako Nomura, Mariko Matsumura, Taichi Murai, Kazufumi Itaya, Yuta Koike, Takaaki Izumi, Ayana Endo, Shin Kato, Yuji Ono, Takahiro Ohshima, Nanase Okazaki, Shimpei Nakagawa, Yasushi Ishii, Yuichiro Fukasawa, Isao Yokota, Takahiro Tsuji, Shuji Nishikawa

  Pathology international 73 10 509 - 519 2023年08月17日 

  Accurate evaluation of human epidermal growth factor receptor type 2 (HER2) expression is crucial for determining chemotherapy regimens in gastric cancer. However, formalin fixation status has been identified as an important factor affecting HER2 assessment reliability. This retrospective cohort study aimed to investigate the correlation between sample collection day (weekday vs. weekend) and source (biopsy vs. surgical specimens) in assessing HER2 expression in patients with unresectable advanced/recurrent gastric cancer. Data were collected from gastric cancer patients who received chemotherapy at a single public hospital in Japan from 2008 to 2021. The analysis included 177 patients (109 men, 68 women) with a median age of 68.0 (21-88) years, and the primary outcome was the HER2 positivity rate. The overall HER2 positivity rate was 18.1%, with higher rates on weekdays (20.0%) compared to weekends (12.8%). Biopsies had higher positivity rates on weekdays (23.9%) but lower rates on weekends (11.1%) than surgical specimens. Significant differences were observed in formalin fixation times between weekdays and weekends for both biopsies and surgical samples. The study findings suggest that longer formalin fixation times on weekends may lead to underestimating HER2 expression, particularly in biopsies. Therefore, it is crucial to be cautious of excessive formalin fixation when collecting samples, especially during weekend biopsies.
• Delphi Method Consensus-Based Identification of Primary Trauma Care Skills Required for General Surgeons in Japan

  Kazuyuki Hirose, Soichi Murakami, Yo Kurashima, Nagato Sato, Saseem Poudel, Kimitaka Tanaka, Aya Matsui, Yoshitsugu Nakanishi, Toshimichi Asano, Takehiro Noji, Yuma Ebihara, Toru Nakamura, Takahiro Tsuchikawa, Toshiaki Shichinohe, Kazufumi Okada, Isao Yokota, Naoto Hasegawa, Satoshi Hirano

  Journal of Acute Care Surgery 13 2 58 - 65 2023年07月31日 

  Purpose: General surgeons at regional hospitals should have the primary trauma care skills necessary to treat critically ill trauma patients to withstand transfer. This study was conducted to identify a consensus on primary trauma care skills for general surgeons.Methods: An initial list of acute care surgical skills was compiled, and revised by six trauma experts (acute care surgeons); 33 skills were nominated for inclusion in the Delphi consensus survey. Participants (councilors of the Japanese Society for Acute Care Surgery) were presented with the list of 33 trauma care skills and were asked (using web-based software) to rate how strongly they agreed or disagreed (using a 5-point Likert scale) with the necessity of each skill for a general surgeon. The reliability of consensus was predefined as Cronbach’s α ≥ 0.8, and trauma care skills were considered as primarily required when rated 4 (agree) or 5 (strongly agree) by ≥ 80% participants.Results: There were 117 trauma care specialists contacted to participate in the Delphi consensus survey panel. In the 1^st round, 85 specialists participated (response rate: 72.6%). In the 2^nd round, 66 specialists participated (response rate: 77.6%). Consensus was achieved after two rounds, reliability using Cronbach’s α was 0.94, and 34 items were identified as primary trauma care skills needed by general surgeons.Conclusion: A consensus-based list of trauma care skills required by general surgeons was developed. This list can facilitate the development of a new trauma training course which has been optimized for general surgeons.
• Comparative pathogenicity of SARS-CoV-2 Omicron subvariants including BA.1, BA.2, and BA.5.

  Tomokazu Tamura, Daichi Yamasoba, Yoshitaka Oda, Jumpei Ito, Tomoko Kamasaki, Naganori Nao, Rina Hashimoto, Yoichiro Fujioka, Rigel Suzuki, Lei Wang, Hayato Ito, Yukie Kashima, Izumi Kimura, Mai Kishimoto, Masumi Tsuda, Hirofumi Sawa, Kumiko Yoshimatsu, Yuki Yamamoto, Tetsuharu Nagamoto, Jun Kanamune, Yutaka Suzuki, Yusuke Ohba, Isao Yokota, Keita Matsuno, Kazuo Takayama, Shinya Tanaka, Kei Sato, Takasuke Fukuhara

  Communications biology 6 1 772 - 772 2023年07月24日 

  The unremitting emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants necessitates ongoing control measures. Given its rapid spread, the new Omicron subvariant BA.5 requires urgent characterization. Here, we comprehensively analyzed BA.5 with the other Omicron variants BA.1, BA.2, and ancestral B.1.1. Although in vitro growth kinetics of BA.5 was comparable among the Omicron subvariants, BA.5 was much more fusogenic than BA.1 and BA.2. Airway-on-a-chip analysis showed that, among Omicron subvariants, BA.5 had enhanced ability to disrupt the respiratory epithelial and endothelial barriers. Furthermore, in our hamster model, in vivo pathogenicity of BA.5 was slightly higher than that of the other Omicron variants and less than that of ancestral B.1.1. Notably, BA.5 gains efficient virus spread compared with BA.1 and BA.2, leading to prompt immune responses. Our findings suggest that BA.5 has low pathogenicity compared with the ancestral strain but enhanced virus spread /inflammation compared with earlier Omicron subvariants.
• Assessment of hepatic veno-occlusive disease/sinusoidal obstruction syndrome using different scanning approaches for the ultrasonographic evaluation of portal vein blood flow and hepatic artery resistive index in hematopoietic stem cell transplant recipients.

  Momoka Kikuchi, Takahito Iwai, Mutsumi Nishida, Yusuke Kudo, Satomi Omotehara, Megumi Sato, Junichi Sugita, Hideki Goto, Isao Yokota, Takanori Teshima

  Journal of medical ultrasonics (2001) 2023年07月04日 

  PURPOSE: Sinusoidal obstruction syndrome (SOS) is a fatal complication of hematopoietic stem cell transplantation (HSCT). Previously, we established a scoring system (Hokkaido ultrasound-based scoring system-10; HokUS-10) comprising 10 ultrasound parameters for SOS diagnosis. In HokUS-10, the portal vein time-averaged flow velocity (PV TAV) and hepatic artery resistive index (HA RI) are measured using subcostal scanning. However, measurement errors and delineation difficulties occur. Therefore, we aimed to prospectively evaluate PV TAV and HA RI measurements obtained via intercostal scanning as an alternative method to subcostal scanning and determine their cutoff values. METHODS: HokUS-10 was administered before and after HSCT. PV TAV and HA RI were measured on subcostal and right intercostal scans. RESULTS: We performed 366 scans on 74 patients. The median value (range) of PV TAV in the main and right portal veins was 15.0 cm/s (2.2-49.6 cm/s) and 10.5 cm/s (1.6-22.0 cm/s), respectively. A low correlation was observed between the two values (r = 0.39, p < 0.01). The highest diagnostic value of the right portal vein was less than 8.0 cm/s. The median value (range) of HA RI in the proper and right hepatic arteries was 0.72 (0.52-1.00) and 0.70 (0.51-1.00), respectively. A strong correlation was observed between the two values (r = 0.65, p < 0.01). The highest diagnostic value of the right HA RI was 0.72 or higher. CONCLUSION: Quantitative measurement of PV TAV and HA RI using intercostal scanning can be appropriately performed as an alternative method to using subcostal scanning.
• Bone metastatic cancer of unknown primary at initial presentation.

  Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Yuki Suzuki, Hamasaki Masanari, Eiji Kondo, Norimasa Iwasaki

  Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 2023年07月03日 

  INTRODUCTION: Cancer of unknown primary (CUP) is a challenging malignancy. The purpose of this study was to investigate the clinical characteristics and prognosis of bone metastatic CUP using the population-based Surveillance, Epidemiology, and End Results (SEER) database. METHODS: From the SEER database, we identified 1908 patients with bone metastatic CUP at initial presentation between 2010 and 2018. Histology was subdivided following International Classification of Diseases for Oncology codes as Adenocarcinoma, Squamous cell, Neuroendocrine, or Carcinoma not otherwise specified (NOS). Cox proportional hazard modeling was applied using factors of age, sex, ethnicity, histological subtype, and therapeutic intervention. RESULTS: Among the 1908 patients, histology was Neuroendocrine in 240 patients, Squamous cell in 201 patients, Adenocarcinoma in 810 patients and NOS in 657 patients. In each subtype, patients tended to be predominantly male and white. Chemotherapy was introduced for 28% of patients and radiation for 34% in the entire cohort. Survival in patients with bone metastatic CUP was unfavorable, with a median survival of 2 months. Among the histological subtypes, Adenocarcinoma showed shorter survival than the other groups. In addition, treatment interventions such as chemotherapy and radiation therapy prolonged survival, particularly for Squamous cell, Adenocarcinoma and NOS, but not for Neuroendocrine. DISCUSSION: Bone metastatic CUP showed extremely poor prognosis, but treatment interventions such as chemotherapy and radiation generally offered survival benefits. Further randomized clinical research is needed to confirm the present results.
• Prognostic impact of LILRB4 expression on tumor-infiltrating cells in resected non-small cell lung cancer.

  Sakiko Kumata, Hirotsugu Notsuda, Mei-Tzu Su, Ryoko Saito-Koyama, Ryota Tanaka, Yuyo Suzuki, Junichi Funahashi, Shota Endo, Isao Yokota, Toshiyuki Takai, Yoshinori Okada

  Thoracic cancer 14 21 2057 - 2068 2023年07月 

  BACKGROUND: Leukocyte immunoglobulin-like receptor subfamily B member 4 (LILRB4/ILT3) is an up-and-coming molecule that promotes immune evasion. We have previously reported that LILRB4 facilitates myeloid-derived suppressor cells (MDSCs)-mediated tumor metastasis in mice. This study aimed to investigate the impact of the LILRB4 expression levels on tumor-infiltrating cells on the prognosis of non-small cell lung cancer (NSCLC) patients. METHODS: We immunohistochemically evaluated the LILRB4 expression levels of completely resected 239 NSCLC specimens. Whether the blocking of LILRB4 on human PBMC-derived CD33+ MDSCs inhibited the migration ability of lung cancer cells was also examined using transwell migration assay. RESULTS: The LILRB4 high group, in which patients with a high LILRB4 expression level on tumor-infiltrating cells, showed a shorter overall survival (OS) (p = 0.013) and relapse-free survival (RFS) (p = 0.0017) compared to the LILRB4 low group. Multivariate analyses revealed that a high LILRB4 expression was an independent factor for postoperative recurrence, poor OS and RFS. Even in the cohort background aligned by propensity score matching, OS (p = 0.023) and RFS (p = 0.0046) in the LILRB4 high group were shorter than in the LILRB4 low group. Some of the LILRB4 positive cells were positive for MDSC markers, CD33 and CD14. Transwell migration assay demonstrated that blocking LILRB4 significantly inhibited the migration of human lung cancer cells cocultured with CD33+ MDSCs. CONCLUSION: Together, signals through LILRB4 on tumor-infiltrating cells, including MDSCs, play an essential role in promoting tumor evasion and cancer progression, impacting the recurrence and poor prognosis of patients with resected NSCLC.
• Factors Affecting Transcranial Motor-Evoked Potential Measurements Using Single-Train Stimulation with an Increased Number of Pulses during Adolescent Scoliosis Surgery: A Prospective Observational Study.

  Takayuki Toki, Noriaki Fujita, Tomohiro Ichikawa, Noriki Ochi, Isao Yokota, Hideki Sudo, Yuji Morimoto

  Journal of clinical medicine 12 13 2023年06月30日 

  Measurement of transcranial motor-evoked potentials (TcMEPs) during scoliosis surgery helps detect postoperative new neurological defects. However, TcMEP interpretation is difficult owing to the influence of intraoperative physiological, pharmacological, and time-related factors as well as stimulation conditions. In this study, we aimed to investigate the effect of the abovementioned factors on TcMEP amplitude using single-train stimulation with an increased number of pulses (STS-INP) during adolescent scoliosis surgery; moreover, we evaluated the complications of TcMEP measurement. We included 50 patients and 706 TcMEP measurements. A total of 1412 TcMEP waveforms were analyzed, each on the bilateral abductor pollicis brevis, tibialis anterior, and abductor hallucis muscles. We estimated the mean difference (95% confidence interval (CI)) and predicted mean difference (95% CI) evaluated using the interquartile range of each factor, based on a mixed-effect model with random intercepts for TcMEP amplitude. The predicted mean differences in TcMEP amplitude were clinically small compared with the actual TcMEP amplitude, suggesting that each factor had a limited effect on TcMEP amplitude. No intraoperative bite injuries or seizures were observed. Using STS-INP during adolescent scoliosis surgery may enable accurate measurement of TcMEP amplitude with neither complications nor the influence of various intraoperative factors.
• 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 

  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.
• NURSE-LED proactive rounding and automatic early-warning score systems to prevent resuscitation incidences among Adults in ward-based Hospitalised patients.

  Ayako Noguchi, Isao Yokota, Tetsuya Kimura, Masaki Yamasaki

  Heliyon 9 6 e17155  2023年06月 

  OBJECTIVES: In this study, we investigated the impact of critical care outreach implemented to overcome the problem of rapid response system (RRS) activation. The aim was to evaluate the impact of nurse-led proactive rounding on the rate of adverse events in a hospital setting using an automatic early-warning score system, without a call-activated team. METHODS: This observational study was conducted at a university hospital in Japan. Beginning in September 2019, critical care outreach via nurse-led proactive rounding of the general ward was conducted, using an automatic early-warning score system. We retrospectively assessed the computerised records of all inpatient days (N = 497,284) of adult inpatients admitted to the hospital from September 2017 to 2020. We compared the adverse event occurrences before and after implementation of the critical care outreach program. The main outcome measures were: unexpected death in the general ward, code blue (an in-hospital resuscitation request code directed towards all staff via broadcast) for non-intensive care unit inpatients and unexpected intensive care unit admissions from the general ward. The secondary outcome was the proportion of patients who received respiratory rate measurement. RESULTS: The incidence rate ratios of the occurrence of unexpected deaths (0.19, 95% confidence interval: 0.04-0.57) and code blue in the general ward (0.15, 95% confidence interval: 0.025-0.50) decreased. There was no change in unexpected intensive care unit admissions from the general ward (1.25, confidence interval: 0.84-1.82). The proportion of patients who received respiratory rate measurement increased (10.2% vs 16.2%). CONCLUSION: Our results suggest that in RRSs, drastic control of the failure of the mechanism to activate a response team may produce positive outcomes. Proactive rounding that bypasses the mechanism to activate a response team component of RRSs may relieve ward nurses of activation failure responsibility and help them overcome the hierarchical hospital structure.
• Effects of ephedrine and phenylephrine on cerebral oxygenation: observational prospective study using near-infrared time-resolved spectroscopy.

  Yasunori Kubo, Tomonori Kubo, Takayuki Toki, Isao Yokota, Yuji Morimoto

  Journal of clinical monitoring and computing 2023年05月27日 

  It has been reported that cerebral oxygenation (ScO2) measured by near infrared spectroscopy is maintained or increased by treatment with ephedrine, whereas almost all previous reports demonstrated that phenylephrine reduced ScO2. As the mechanism of the latter, the interference of the extracranial blood flow, that is extracranial contamination, has been suspected. Accordingly, in this prospective observational study, we utilized time-resolved spectroscopy (TRS), in which the effect of extracranial contamination is thought to be minimal, and evaluated whether the same result was obtained. We measured the changes in ScO2 as well as the total cerebral hemoglobin concentration (tHb) after treatment with ephedrine or phenylephrine during laparoscopic surgery by using a tNIRS-1 (Hamamatsu Photonics, Hamamatsu, Japan), which is a commercial instrument utilizing TRS. Based on a mixed-effects model with random intercepts for ScO2 or tHb including mean blood pressure, the mean difference and 95% confidence interval were evaluated as well as the predicted mean difference and its confidence interval using the interquartile range of mean blood pressure. Fifty treatments with ephedrine or phenylephrine were done. The mean differences of ScO2 were less than 0.1% and the predicted mean differences were less than 1.1% for the two drugs. The mean differences of tHb were less than 0.02 μM and the predicted mean differences were less than 0.2 μM for the drugs. The changes in ScO2 and tHb after treatments with ephedrine and phenylephrine were very small and clinically insignificant when measured by TRS. Previous reports about phenylephrine may have been affected by extracranial contamination.
• The AppCare-HF randomized clinical trial: a feasibility study of a novel self-care support mobile app for individuals with chronic heart failure

  Takashi Yokota, Arata Fukushima, Miyuki Tsuchihashi-Makaya, Takahiro Abe, Shingo Takada, Takaaki Furihata, Naoki Ishimori, Takeo Fujino, Shintaro Kinugawa, Masayuki Ohta, Shigeo Kakinoki, Isao Yokota, Akira Endoh, Masanori Yoshino, Hiroyuki Tsutsui

  European Heart Journal - Digital Health 4 4 325 - 336 2023年05月10日 

  Abstract Aims We evaluated a self-care intervention with a novel mobile application (app) in chronic heart failure (HF) patients. To facilitate patient-centred care in HF management, we developed a self-care support mobile app to boost HF patients’ optimal self-care. Methods and results We conducted a multicentre, randomized, controlled study evaluating the feasibility of the self-care support mobile app designed for use by HF patients. The app consists of a self-monitoring assistant, education, and automated alerts of possible worsening HF. The intervention group received a tablet personal computer (PC) with the self-care support app installed, and the control group received a HF diary. All patients performed self-monitoring at home for 2 months. Their self-care behaviours were evaluated by the European Heart Failure Self-Care Behaviour Scale. We enrolled 24 outpatients with chronic HF (ages 31–78 years; 6 women, 18 men) who had a history of HF hospitalization. During the 2 month study period, the intervention group (n = 13) showed excellent adherence to the self-monitoring of each vital sign, with a median [interquartile range (IQR)] ratio of self-monitoring adherence for blood pressure, body weight, and body temperature at 100% (92–100%) and for oxygen saturation at 100% (91–100%). At 2 months, the intervention group’s self-care behaviour score was significantly improved compared with the control group (n = 11) [median (IQR): 16 (16–22) vs. 28 (20–36), P = 0.02], but the HF Knowledge Scale, the General Self-Efficacy Scale, and the Short Form-8 Health Survey scores did not differ between the groups. Conclusion The novel mobile app for HF is feasible.
• A machine-learning-based prediction of non-home discharge among acute heart failure patients

  Akira Okada, Hidehiro Kaneko, Masaaki Konishi, Kentaro Kamiya, Tadafumi Sugimoto, Satoshi Matsuoka, Isao Yokota, Yuta Suzuki, Satoko Yamaguchi, Hidetaka Itoh, Katsuhito Fujiu, Nobuaki Michihata, Taisuke Jo, Hiroki Matsui, Kiyohide Fushimi, Norifumi Takeda, Hiroyuki Morita, Hideo Yasunaga, Issei Komuro

  Clinical Research in Cardiology 2023年05月03日 

  Abstract Background Scarce data on factors related to discharge disposition in patients hospitalized for acute heart failure (AHF) were available, and we sought to develop a parsimonious and simple predictive model for non-home discharge via machine learning. Methods This observational cohort study using a Japanese national database included 128,068 patients admitted from home for AHF between April 2014 and March 2018. The candidate predictors for non-home discharge were patient demographics, comorbidities, and treatment performed within 2 days after hospital admission. We used 80% of the population to develop a model using all 26 candidate variables and using the variable selected by 1 standard-error rule of Lasso regression, which enhances interpretability, and 20% to validate the predictive ability. Results We analyzed 128,068 patients, and 22,330 patients were not discharged to home; 7,879 underwent in-hospital death and 14,451 were transferred to other facilities. The machine-learning-based model consisted of 11 predictors, showing a discrimination ability comparable to that using all the 26 variables (c-statistic: 0.760 [95% confidence interval, 0.752–0.767] vs. 0.761 [95% confidence interval, 0.753–0.769]). The common 1SE-selected variables identified throughout all analyses were low scores in activities of daily living, advanced age, absence of hypertension, impaired consciousness, failure to initiate enteral alimentation within 2 days and low body weight. Conclusions The developed machine learning model using 11 predictors had a good predictive ability to identify patients at high risk for non-home discharge. Our findings would contribute to the effective care coordination in this era when HF is rapidly increasing in prevalence.
• Quantitative diagnostic algorithm using endocytoscopy for superficial nonampullary duodenal epithelial tumors.

  Marina Kubo, Shoko Ono, Isao Yokota, Shogo Matsumoto, Yusuke Nishimura, Masayoshi Ono, Keiko Yamamoto, Naoya Sakamoto

  Journal of gastroenterology and hepatology 38 9 1496 - 1502 2023年05月02日 

  BACKGROUND AND AIM: Optical biopsy using endocytoscopy for superficial nonampullary duodenal epithelial tumors (SNADETs) is practical; however, a diagnostic algorithm has not been established. The aim of this study was to determine correlations of endocytoscopic findings of SNADETs with histology using computer analysis and to establish an algorithm. METHODS: Endocytoscopic images and histological images of duodenal lesions from 70 patients were retrospectively collected. The numbers of glands and densely stained areas with methylene blue (DSMs) per 1 mm2 and the percentage of DSMs per screen in endocytoscopy were determined. Moreover, correlations in DSMs and glands between endocytoscopy and histological images were analyzed. Histopathological diagnoses were assessed according to the revised Vienna classification. The primary outcome was correlation between the number of glands in endocytoscopy and that in histology. Finally, a diagnostic algorithm for endoscopic intervention of SNADETs with a statistical program command was established. RESULTS: The number of glands in endocytoscopic images was correlated with that in histopathological images (ρ 0.64, P < 0.001). There were significant differences in the mean number of glands between category 4/5 and category 3 (P = 0.03) and the mean percentage of DSMs between category 4/5 and category 1 (P < 0.001). When the cutoffs for the number of glands and percentage of DSMs were set at 47 per 1 mm2 and 20.8% in one screen, respectively, the area under the ROC curve was 0.89. CONCLUSIONS: Endocytoscopic images of SNADETs reflect histopathological atypia, and computer analysis provides a practical diagnostic algorithm for endoscopic intervention.
• Safety and efficacy of tisagenlecleucel in patients with relapsed or refractory B-cell lymphoma: the first real-world evidence in Japan.

  Hideki Goto, Toshio Kitawaki, Nobuharu Fujii, Koji Kato, Yasushi Onishi, Noriko Fukuhara, Takuji Yamauchi, Kazunori Toratani, Hiroki Kobayashi, Shota Yoshida, Masatoshi Shimo, Koichi Onodera, Hajime Senjo, Masahiro Onozawa, Kenji Hirata, Isao Yokota, Takanori Teshima

  International journal of clinical oncology 28 6 816 - 826 2023年04月18日 

  BACKGROUND: Tisagenlecleucel, an autologous CD19-directed T-cell immunotherapy, can induce a durable response in adult patients with relapsed/refractory (r/r) B-cell lymphoma. METHODS: To elucidate the outcome of chimeric antigen receptor (CAR) T-cell therapy in Japanese, we retrospectively analyzed the outcomes of 89 patients who received tisagenlecleucel for r/r diffuse large B-cell lymphoma (n = 71) or transformed follicular lymphoma (n = 18). RESULTS: With a median follow-up of 6.6-months, 65 (73.0%) patients achieved a clinical response. The overall survival (OS) and event-free survival (EFS) rates at 12 months were 67.0% and 46.3%, respectively. Overall, 80 patients (89.9%) had cytokine release syndrome (CRS), and 6 patients (6.7%) had a grade ≥ 3 event. ICANS occurred in 5 patients (5.6%); only 1 patient had grade 4 ICANS. Representative infectious events of any grade were cytomegalovirus viremia, bacteremia and sepsis. The most common other adverse events were ALT elevation, AST elevation, diarrhea, edema, and creatinine elevation. No treatment-related mortality was observed. A Sub-analysis showed that a high metabolic tumor volume (MTV; ≥ 80 ml) and stable disease /progressive disease before tisagenlecleucel infusion were both significantly associated with a poor EFS and OS in a multivariate analysis (P < 0.05). Notably, the combination of these 2 factors efficiently stratified the prognosis of these patients (HR 6.87 [95% CI 2.4-19.65; P < 0.05] into a high-risk group). CONCLUSION: We report the first real-world data on tisagenlecleucel for r/r B-cell lymphoma in Japan. Tisagenlecleucel is feasible and effective, even in late line treatment. In addition, our results support a new algorithm for predicting the outcomes of tisagenlecleucel.
• Enhanced mitochondrial oxidative metabolism in peripheral blood mononuclear cells is associated with fatty liver in obese young adults

  Ryosuke Shirakawa, Takayuki Nakajima, Aya Yoshimura, Yukako Kawahara, Chieko Orito, Miwako Yamane, Haruka Handa, Shingo Takada, Takaaki Furihata, Arata Fukushima, Naoki Ishimori, Masao Nakagawa, Isao Yokota, Hisataka Sabe, Satoshi Hashino, Shintaro Kinugawa, Takashi Yokota

  Scientific Reports 13 1 5203 - 5203 2023年03月30日 

  Abstract Systemic inflammation underlies the association between obesity and nonalcoholic fatty liver disease (NAFLD). Here, we investigated functional changes in leukocytes’ mitochondria in obese individuals and their associations with NAFLD. We analyzed 14 obese male Japanese university students whose body mass index was > 30 kg/m² and 15 healthy age- and sex-matched lean university students as controls. We observed that the mitochondrial oxidative phosphorylation (OXPHOS) capacity with complex I + II-linked substrates in peripheral blood mononuclear cells (PBMCs), which was measured using a high-resolution respirometry, was significantly higher in the obese group versus the controls. The PBMCs’ mitochondrial complex IV capacity was also higher in the obese subjects. All of the obese subjects had hepatic steatosis defined by a fatty liver index (FLI) score ≥ 60, and there was a positive correlation between their FLI scores and their PBMCs’ mitochondrial OXPHOS capacity. The increased PBMCs’ mitochondrial OXPHOS capacity was associated with insulin resistance, systemic inflammation, and higher serum levels of interleukin-6 in the entire series of subjects. Our results suggest that the mitochondrial respiratory capacity is increased in the PBMCs at the early stage of obesity, and the enhanced PBMCs’ mitochondrial oxidative metabolism is associated with hepatic steatosis in obese young adults.
• Amputation surgery associated with shortened survival in patients with localized soft tissue sarcoma.

  Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Ryosuke Hishimura, Yuki Suzuki, Masanari Hamasaki, Akira Iwata, Eiji Kondo, Norimasa Iwasaki

  Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 2023年03月15日 

  BACKGROUND: The objectives of this study were to clarify whether localized extremity soft tissue sarcoma (STS) patients who underwent amputation surgery experienced worsened survival and to identify those patients for whom amputation surgery worsened survival. METHODS: Using the Surveillance, Epidemiology, and End Results database, we identified 8897 patients with localized extremity STS between 1983 and 2016. Of these 6431 patients, 733 patients underwent amputation surgery (Amputation group), and 5698 underwent limb-sparing surgery (Limb-sparing group). RESULTS: After adjusting for patient background by propensity score matching, a total of 1346 patients were included. Patients in the Amputation group showed worsened survival (cancer-specific survival (CSS): hazard ratio (HR) = 1.42, 95% confidence interval (CI) 1.15-1.75, overall survival (OS): HR = 1.41, 95%CI 1.20-1.65). In subclass analysis, patients with high-grade STS, spindle cell sarcoma and liposarcoma in the Amputation group showed shortened survival (high-grade-CSS: HR = 1.44, 95%CI 1.16-1.77, OS: HR = 1.38, 95%CI 1.18-1.62; spindle cell sarcoma-CSS: HR = 4.75, 95%CI 1.56-14.4, OS: HR = 2.32, 95%CI 1.45-3.70; liposarcoma-CSS: HR = 2.91, 95%CI 1.54-5.50, OS: HR = 2.32, 95%CI 1.45-3.70). CONCLUSIONS: Survival was shortened in localized extremity STS patients who received amputation surgery.
• A Multicenter Prospective Interventional Trial of Therapeutic Angiogenesis Using Bone Marrow-Derived Mononuclear Cell Implantation for Patients With Critical Limb-Threatening Ischemia Caused by Thromboangiitis Obliterans.

  Ayumu Fujioka, Kenji Yanishi, Arito Yukawa, Kojiro Imai, Isao Yokota, Kei Fujikawa, Ayumu Yamada, Akari Naito, Keisuke Shoji, Hirofumi Kawamata, Yukihito Higashi, Tomoaki Ishigami, Ken-Ichiro Sasaki, Syuhei Tara, Koichiro Kuwahara, Satoshi Teramukai, Satoaki Matoba

  Circulation journal : official journal of the Japanese Circulation Society 87 9 1229 - 1237 2023年03月10日 

  BACKGROUND: Thromboangiitis obliterans (TAO) can lead to the development of critical limb-threatening ischemia (CLTI). Despite conventional treatments, such as smoking cessation or revascularization, young patients (<50 years) still require limb amputation. Therapeutic angiogenesis using bone marrow-derived mononuclear cell (BM-MNC) implantation has been tested and shown to have reasonable efficacy in CLTI. In this multicenter prospective clinical trial, we evaluated the safety and efficacy of BM-MNC implantation in CLTI patients with TAO.Methods and Results: We enrolled 22 CLTI patients with skin perfusion pressure (SPP) <30 mmHg. The primary endpoint of this trial is the recovery of SPP in the treated limb after a 180-day follow-up period. Secondary endpoints include the pain scale score and transcutaneous oxygen pressure (TcPO2). One patient dropped out during follow-up, leaving 21 patients (mean age 48 years, 90.5% male, Fontaine Class IV) for analysis. BM-MNC implantation caused no serious adverse events and increased SPP by 1.5-fold compared with baseline. Surprisingly, this effect was sustained over the longer term at 180 days. Secondary endpoints also supported the efficacy of this novel therapy in relieving pain and increasing TcPO2. Major amputation-free and overall survival probabilities at 3 years among all enrolled patients were high (95.5% and 89.5%, respectively). CONCLUSIONS: BM-MNC implantation showed safety and significant efficacy in CLTI patients with TAO.
• Serum Lactate Dehydrogenase Level One Week after Admission Is the Strongest Predictor of Prognosis of COVID-19: A Large Observational Study Using the COVID-19 Registry Japan.

  Sho Nakakubo, Yoko Unoki, Koji Kitajima, Mari Terada, Hiroyuki Gatanaga, Norio Ohmagari, Isao Yokota, Satoshi Konno

  Viruses 15 3 2023年03月02日 

  Clinical features of COVID-19 are diverse, and a useful tool for predicting clinical outcomes based on clinical characteristics of COVID-19 is needed. This study examined the laboratory values and trends that influence mortality in hospitalised COVID-19 patients. Data on hospitalised patients enrolled in a registry study in Japan (COVID-19 Registry Japan) were obtained. Patients with records on basic information, outcomes, and laboratory data on the day of admission (day 1) and day 8 were included. In-hospital mortality was set as the outcome, and associated factors were identified by multivariate analysis using the stepwise method. A total of 8860 hospitalised patients were included. The group with lactate dehydrogenase (LDH) levels >222 IU/L on day 8 had a higher mortality rate compared to the group with LDH levels ≤222 IU/L. Similar results were observed in subgroups formed by age, body mass index (BMI), underlying disease, and mutation type, except for those aged <50 years. When age, sex, BMI, underlying disease, and laboratory values on days 1 and 8 were tested for factors strongly associated with in-hospital mortality, LDH on day 8 was most strongly associated with mortality. LDH level on day 8 was the strongest predictor of in-hospital mortality in hospitalised COVID-19 patients, indicating its potential usefulness in post-treatment decision-making in severe COVID-19 cases.
• Correction to: Refined ultrasonographic criteria for sinusoidal obstruction syndrome after hematopoietic stem cell transplantation.

  Nishida M, Sugita J, Takahashi S, Iwai T, Sato M, Kudo Y, Omotehara S, Horie T, Sakano R, Shibuya H, Yokota I, Iguchi A, Teshima T

  International journal of hematology 2023年03月
• Simulation studies on the estimation of sensitivity and specificity in the absence of a gold standard and with rare positive frequencies

  Tasuku Inao, Kazufumi Okada, Yichi Yang, Isao Yokota

  COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION 2023年03月 

  In the absence of a gold standard, sensitivity and specificity could be evaluated using the Bayesian latent class model underlying true positives and true negatives. However, when the frequency of positivity is limited owing to low prevalence, the estimates may be strongly influenced by prior information or small-sample bias. In this study, we evaluated the performance of the Bayesian latent class model with two independent tests under a rare frequency of positivity, varying the strength and way of giving prior information under the conditional independence assumption is satisfied. Throughout the simulation experiments, a small-sample bias led to underestimation and overestimation when the frequency of positivity was low. Furthermore, we observed that placing an informative prior distribution for only one of the two tests resulted in a constant bias of sensitivity or specificity for the other test, regardless of the strength of the prior information.
• Age‐Dependent Association Between Modifiable Risk Factors and Incident Cardiovascular Disease

  Hidehiro Kaneko, Yuichiro Yano, Akira Okada, Hidetaka Itoh, Yuta Suzuki, Isao Yokota, Kojiro Morita, Katsuhito Fujiu, Nobuaki Michihata, Taisuke Jo, Satoko Yamaguchi, Norifumi Takeda, Hiroyuki Morita, Koichi Node, Toshimasa Yamauchi, Masaomi Nangaku, Takashi Kadowaki, John W. McEvoy, Carolyn S. P. Lam, Hideo Yasunaga, Issei Komuro

  Journal of the American Heart Association 12 2 2023年01月17日 

  Background

  There have been limited data examining the age‐dependent relationship of wide‐range risk factors with the incidence of each subtype of cardiovascular disease (CVD) event. We assessed age‐related associations between modifiable risk factors and the incidence of CVD.

  Methods and Results

  We analyzed 3 027 839 participants without a CVD history enrolled in the JMDC Claims Database (mean age, 44.8±11.0 years; 57.6% men). Each participant was categorized as aged 20 to 49 years (n=2 008 559), 50 to 59 years (n=712 273), and 60 to 75 years (n=307 007). Using Cox proportional hazards models and the relative risk reduction, we identified associations between risk factors and incident CVD, consisting of myocardial infarction, angina pectoris, stroke, and heart failure (HF). We assessed whether the association of risk factors for developing CVD would be modified by age category. Over a mean follow‐up of 1133 days, 6315 myocardial infarction, 56 447 angina pectoris, 28 079 stroke, and 56 369 HF events were recorded. The incidence of myocardial infarction, angina pectoris, stroke, and HF increased with age category. Hazard ratios of obesity, hypertension, and diabetes in the multivariable Cox regression analyses for myocardial infarction, angina pectoris, stroke, and HF decreased with age category. The relative risk reduction of obesity, hypertension, and diabetes for CVD events decreased with age category. For example, the relative risk reduction of hypertension for HF decreased from 59.2% in participants aged 20 to 49 years to 38.1% in those aged 60 to 75 years.

  Conclusions

  The contribution of modifiable risk factor to the development of CVD is greater in younger compared with older individuals. Preventive efforts for risk factor modification may be more effective in younger people.

• 単一の体液の同定を目的としたSingle-target multiplex RT-PCR法の検証─5種の体液を対象としたMulti-target multiplex RT-PCR法との比較─

  Tomoko Akutsu, Isao Yokota, Ken Watanabe, Kochi Toyomane, Takayuki Yamagishi, Koichi Sakurada

  Japanese Journal of Forensic Science and Technology 2023年
• Comparison of Access Route for Endovascular Treatment by Time-Spatial Labeling Inversion Pulse (Time-SLIP) MRA and Contrast-Enhanced MRA

  Satoshi Kobayashi, Toshiya Osanai, Taku Sugiyama, Noriyuki Fujima, Ryo Takagi, Isao Yokota, Akiyoshi Hamaguchi, Toshitaka Nakamura, Kazutoshi Hida, Miki Fujimura

  Journal of Neuroendovascular Therapy 2023年
• Risk of post-extraction bleeding with direct oral anticoagulant compared with warfarin: Retrospective cohort study using large scale claims data in Japan.

  Sachiko Ono, Miho Ishimaru, Isao Yokota, Takaaki Konishi, Akira Okada, Yosuke Ono, Hiroki Matsui, Shunsuke Itai, Kazumichi Yonenaga, Kanata Tonosaki, Rinji Watanabe, Kazuto Hoshi, Hideo Yasunaga

  Thrombosis research 222 24 - 30 2022年12月20日 

  INTRODUCTION: Comparative safety of direct oral anticoagulants vs. warfarin in patients undergoing tooth extraction remains unclear. We compared the incidence of post-extraction bleeding between patients taking warfarin and those taking direct oral anticoagulants (DOACs) using administrative claims data. MATERIALS AND METHODS: We identified outpatients on anticoagulant therapy who underwent permanent tooth extraction between 2015 and 2020 and categorized them into the warfarin and DOAC groups based on medication prescribed within six months prior to tooth extraction. We used the overlap propensity score weighting method to balance the baseline characteristics between the groups and compared the incidence of post-extraction bleeding within seven days after tooth extraction. RESULTS: Among 5253 eligible patients, those in the DOAC group (n = 3696) were older and less frequently prescribed antiplatelets than those in the warfarin group (n = 1557). The distribution of tooth extraction type and number of teeth extracted in a single procedure did not differ between the groups. The unadjusted incidences of post-extraction bleeding in the warfarin and DOAC groups were 35 (2.2 %) and 71 (1.9 %), respectively. Moreover, the overlap weighting analysis showed that the adjusted odds ratio of post-extraction bleeding in the DOAC group in comparison with that in the warfarin group was 0.84 (95 % confidence interval, 0.54-1.31). CONCLUSION: The incidence of post-extraction bleeding in patients taking DOACs was comparable to that in patients taking warfarin. The findings suggest that dentists and physicians should exercise the same degree of caution when extracting teeth in patients on DOACs and those on warfarin in terms of post-extraction bleeding.
• Impact of body mass index on in-hospital mortality in older patients hospitalized for bacterial pneumonia with non-dialysis-dependent chronic kidney disease.

  Akira Okada, Satoko Yamaguchi, Taisuke Jo, Isao Yokota, Sachiko Ono, Kayo Ikeda Kurakawa, Masaomi Nangaku, Toshimasa Yamauchi, Takashi Kadowaki

  BMC geriatrics 22 1 950 - 950 2022年12月09日 

  BACKGROUND: Low body mass index (BMI) in older individuals with decreased kidney function is important because of its association with poor prognosis and frailty. Herein, we aimed to clarify the association between BMI and in-hospital mortality among older patients with non-dialysis-dependent chronic kidney disease (CKD) stratified by kidney function. METHODS: Using data from the Medical Vision Database, this multicentre cohort study included people aged ≥ 60 years with an estimated glomerular filtration rate of < 60 ml/min/1.73 m2 but without dialysis dependency, hospitalised for bacterial pneumonia during 2014-2019. We compared the risk of in-hospital death between patients with BMI categories based on the quartiles (low, medium-low, medium-high, and high) setting medium-high BMI as a reference. We further assessed the association with BMI using a cubic spline, setting BMI as a nonlinear continuous variable and a BMI of 22 kg/m2 as a reference. We also evaluated the association between BMI and kidney function using a generalised additive model adjusted for interaction terms between nonlinear continuous BMI and kidney function. RESULTS: We obtained data for 3,952 patients, with 350 (8.9%) in-hospital deaths. When compared with medium-high BMI, low BMI was associated with an increased risk of death and longer hospital stay, whereas the other two categories were comparable. Models using a cubic spline showing an association between BMI and in-hospital death showed an L-shaped curve; BMI < 22.0 kg/m2 was associated with an increased risk for mortality, and at a BMI of 18.5 kg/m2, the odds ratio was 1.43 with a 95% confidence interval of 1.26-1.61 when compared with a BMI of 22.0 kg/m2. Analysis of the interactive effects of kidney function using the generalised additive model showed that a protective association of high BMI tapered along with decreased kidney function. CONCLUSIONS: This cohort study suggests not only that lower BMI and low kidney function are associated with in-hospital mortality independently but also that the protective effects of high BMI weaken as kidney function decreases via the analysis of the interaction terms. This study highlights the necessity for the prevention of underweight and demonstrates the interaction between BMI and kidney function in older patients with non-dialysis-dependent CKD.
• Clot-regression effects of rivaroxaban in venous thromboembolism treatment in cancer patients-a prospective interventional study.

  Takai S, Nakanishi N, Yokota I, Imai K, Yamada A, Kawasaki T, Kasahara T, Okada T, Sawada T, Matoba S

  Scientific reports 2022年12月
• Interaction of Blood Pressure and Glycemic Status in Developing Cardiovascular Disease: Analysis of a Nationwide Real-World Database.

  Suzuki Y, Kaneko H, Yano Y, Okada A, Itoh H, Matsuoka S, Yokota I, Imaizumi T, Fujiu K, Michihata N, Jo T, Takeda N, Morita H, Node K, Yasunaga H, Komuro I

  Journal of the American Heart Association 2022年12月
• Impact of sustained hypertension on new cardiovascular events in patients with type 2 diabetes: KAMOGAWA-HBP study.

  Takashi Yoshimura, Emi Ushigome, Shinnosuke Hata, Maya Takegami, Goji Hasegawa, Toru Tanaka, Sei Tsunoda, Masayoshi Ohnishi, Isao Yokota, Hidetaka Ushigome, Nobuko Kitagawa, Mai Asano, Masahide Hamaguchi, Masahiro Yamazaki, Michiaki Fukui

  Journal of clinical hypertension (Greenwich, Conn.) 24 12 1561 - 1567 2022年12月 

  We have previously shown that masked hypertension (MH) and sustained hypertension (SH) contribute to the progression of diabetic nephropathy. Although the risk of target organ damage and cardiovascular events in MH and SH is significantly higher than that in normotension and white coat hypertension, the role of MH or SH in cardiovascular events has never been reported in studies specific to diabetic patients. Therefore, in this study, we aimed to determine whether blood pressure control status contributes to the development of new cardiovascular events. A longitudinal study of 1082 patients with type 2 diabetes mellitus and no history of cardiovascular events was conducted. Patients were instructed to have their blood pressure measured three times, every morning and evening, for 14 consecutive days. Hypertension status was classified into four groups based on the systolic blood pressure measurements in the clinic and at home. The primary endpoint was the first cardiovascular event. After a median follow-up of 7.0 (interquartile range, 4.0-9.0) years, 119 patients developed cardiovascular events. The hazard ratio (95% confidence interval) for the risk of developing cardiovascular events was significantly higher in the SH group than in the controlled blood pressure group (1.63 [1.02-2.59]). SH is a useful predictor of cardiovascular events. Both at home and in the clinic, blood pressure monitoring should be assessed in routine clinical practice to predict future cardiovascular events in patients with type 2 diabetes.
• Latent trajectory modelling of pulmonary artery pressure in systemic sclerosis: a retrospective cohort study.

  Takashi Kida, Keiichi Matsuzaki, Isao Yokota, Nozomu Kawase, Masatoshi Kadoya, Hironori Inoue, Yuji Kukida, Shunya Kaneshita, Takuya Inoue, Makoto Wada, Masataka Kohno, Wataru Fukuda, Yutaka Kawahito, Taku Iwami

  RMD open 8 2 2022年12月 

  OBJECTIVES: To visualise the trajectories of pulmonary arterial pressure (PAP) in systemic sclerosis (SSc) and identify the clinical phenotypes for each trajectory, by applying latent trajectory modelling for PAP repeatedly estimated by echocardiography. METHODS: This was a multicentre, retrospective cohort study conducted at four referral hospitals in Kyoto, Japan. Patients with SSc who were treated at study sites between 2008 and 2021 and who had at least three echocardiographic measurements of systolic PAP (sPAP) were included. A group-based trajectory model was applied to the change in sPAP over time, and patients were classified into distinct subgroups that followed similar trajectories. Pulmonary hypertension (PH)-free survival was compared for each trajectory. Multinomial logistic regression analysis was performed for baseline clinical characteristics associated with trajectory assignment. RESULTS: A total of 236 patients with 1097 sPAP measurements were included. We identified five trajectories: rapid progression (n=9, 3.8%), early elevation (n=30, 12.7%), middle elevation (n=54, 22.9%), late elevation (n=24, 10.2%) and low stable (n=119, 50.4%). The trajectories, in the listed order, showed progressively earlier elevation of sPAP and shorter PH-free survival. In the multinomial logistic regression analysis with the low stable as a reference, cardiac involvement was associated with rapid progression, diffuse cutaneous SSc was associated with early elevation and anti-centromere antibody was associated with middle elevation; older age of onset was associated with all three of these trajectories. CONCLUSION: The pattern of changes in PAP over time in SSc can be classified into five trajectories with distinctly different clinical characteristics and outcomes.
• Differential role of mucus plugs in asthma: Effects of smoking and association with airway inflammation.

  Akira Oguma, Kaoruko Shimizu, Hirokazu Kimura, Naoya Tanabe, Susumu Sato, Isao Yokota, Michiko Takimoto-Sato, Machiko Matsumoto-Sasaki, Yuki Abe, Nozomu Takei, Houman Goudarzi, Masaru Suzuki, Hironi Makita, Toyohiro Hirai, Masaharu Nishimura, Satoshi Konno

  Allergology international : official journal of the Japanese Society of Allergology 72 2 262 - 270 2022年11月16日 

  BACKGROUND: The physiological importance of mucus plugs in computed tomography (CT) imaging is being increasingly recognized. However, whether airway inflammation and smoking affect the association between mucus plugs and clinical-physiological outcomes in asthma remains to be elucidated. The objective of this study is to examine how airway inflammation and/or smoking affect the correlation of CT-based mucus plug scores with exacerbation frequency and airflow limitation indices in asthma. METHODS: A total of 168 patients with asthma who underwent chest CT and sputum evaluation were enrolled and classified in eosinophilic asthma (EA; n = 103) and non-eosinophilic asthma (NEA; n = 65) groups based on sputum eosinophil percentage (cut-off: 3%). The mucus plug score was defined as the number of lung segments with mucus plugs seen on CT. RESULTS: More mucus plugs were detected on CT scans in the EA group than in the NEA group, regardless of smoking status. Mucus plug score and exacerbation frequency during one year after enrollment were significantly associated in the EA group but not in the NEA group after adjusting for demographics, blood eosinophil count, and fractional exhaled nitric oxide. Mucus plug score was associated with percentage of predicted forced expiratory volume in 1 s in non-smoking individuals in the EA and NEA group and in smoking individuals in the EA group but not in the NEA group after adjusting for demographics. CONCLUSIONS: The association of mucus plug score with exacerbation frequency and reduced lung function may vary due to airway inflammatory profile and smoking status in asthma.
• Threshold of BMI for the Development of Hypertension among Japanese Adults.

  Yuta Suzuki, Hidehiro Kaneko, Yuichiro Yano, Akira Okada, Yohei Hashimoto, Hidetaka Itoh, Satoshi Matsuoka, Isao Yokota, Katsuhito Fujiu, Nobuaki Michihata, Taisuke Jo, Norifumi Takeda, Hiroyuki Morita, Kentaro Kamiya, Atsuhiko Matsunaga, Junya Ako, Koichi Node, Hideo Yasunaga, Issei Komuro

  The Journal of nutrition 152 11 2565 - 2571 2022年11月 

  BACKGROUND: The optimal value of BMI for the development of hypertension and the influence of BMI on the development of stage 1 or stage 2 hypertension remain unclear. OBJECTIVES: We sought to identify the BMI threshold for the prevention of hypertension and how changes in BMI would influence the risk of developing hypertension. METHODS: We analyzed 1,262,356 participants (median age: 43 y; 50.9% men) with normal blood pressure [BP; systolic BP (SBP) <120 mmHg and diastolic BP (DBP) <80 mmHg] or elevated BP (SBP: 120-129 mmHg and DBP <80 mmHg). The primary outcome was stage 1 (SBP 130-139 mmHg or DBP 80-89 mmHg) or stage 2 hypertension (SBP ≥140 mmHg or DBP ≥90 mmHg). We analyzed the relation between baseline BMI, change in BMI, and the risk of developing hypertension using generalized additive models with a smoothing spline. RESULTS: During the median follow-up of 851 d, 341,212 cases of stage 1 hypertension and 70,968 cases of stage 2 hypertension were detected. The risk of developing stage 1 or stage 2 hypertension increased steeply after BMI (kg/m2) exceeded 20. The annual change in BMI was positively correlated with the risk of developing stage 1 or 2 hypertension. Contour mapping using generalized additive models demonstrated an additive increase in the risk of developing hypertension with higher baseline BMI and increases in BMI over 1 y. Body-weight gain increases the risk of developing hypertension even in underweight or normal-weight individuals based on the WHO classification. CONCLUSIONS: In Japanese adults with normal or elevated BP, the risk of developing hypertension increased with BMI when baseline BMI was >20. Body-weight gain additively interacted with baseline BMI during hypertension development. Our results underscore the importance of maintaining body weight in preventing the development of hypertension.
• SARS-CoV-2 Omicron detection by antigen tests using saliva.

  Kaoru Murakami, Sumio Iwasaki, Satoshi Oguri, Kumiko Tanaka, Rigel Suzuki, Kasumi Hayasaka, Shinichi Fujisawa, Chiaki Watanabe, Satoshi Konno, Isao Yokota, Takasuke Fukuhara, Masaaki Murakami, Takanori Teshima

  Journal of clinical virology plus 2 4 100109 - 100109 2022年11月 

  The Omicron emerged in November 2021 and became the predominant SARS-CoV-2 variant globally. It spreads more rapidly than ancestral lineages and its rapid detection is critical for the prevention of disease outbreaks. Antigen tests such as immunochromatographic assay (ICA) and chemiluminescent enzyme immunoassay (CLEIA) yield results more quickly than standard polymerase chain reaction (PCR). However, their utility for the detection of the Omicron variant remains unclear. We herein evaluated the performance of ICA and CLEIA in saliva from 51 patients with Omicron and 60 PCR negative individuals. The sensitivity and specificity of CLEIA were 98.0% (95%CI: 89.6-100.0%) and 100.0% (95%CI: 94.0-100.0%), respectively, with fine correlation with cycle threshold (Ct) values. The sensitivity and specificity of ICA were 58.8% (95%CI: 44.2-72.4%) and 100.0% (95%CI: 94.0-100.0%), respectively. The sensitivity of ICA was 100.0% (95%CI: 80.5-100.0%) when PCR Ct was less than 25. The Omicron can be efficiently detected in saliva by CLEIA. ICA also detects high viral load Omicron using saliva.
• DLBCLにおける適切なエンドポイントはEFS36である

  泉山 康, 稲尾 翼, 後藤 秀樹, 原田 晋平, 千丈 創, 須藤 啓斗, 橋口 淳一, 小笠原 励起, 佐賀 智之, 五十嵐 哲祥, 若狭 健太郎, 笠原 郁美, 武田 紫, 山口 圭介, 重松 明男, 高畑 むつみ, 藤本 勝也, 長谷山 美仁, 永嶋 貴博, 酒井 基, 柿木 康孝, 黒澤 光俊, 横田 勲, 豊嶋 崇徳

  日本血液学会学術集会 84回 916 - 916 2022年10月
• Home-measured pulse pressure is a predictor of cardiovascular disease in type 2 diabetes: The KAMOGAWA-HBP study.

  Maya Takegami, Emi Ushigome, Shinnosuke Hata, Takashi Yoshimura, Nobuko Kitagawa, Goji Hasegawa, Toru Tanaka, Masayoshi Ohnishi, Sei Tsunoda, Isao Yokota, Hidetaka Ushigome, Mai Asano, Masahide Hamaguchi, Masahiro Yamazaki, Michiaki Fukui

  Nutrition, metabolism, and cardiovascular diseases : NMCD 32 10 2330 - 2337 2022年10月 

  BACKGROUND AND AIMS: Pulse pressure (PP) is a prognostic predictor of cardiovascular mortality. This retrospective cohort study aimed to investigate the association between home PP measurements and cardiovascular disease in patients with type 2 diabetes. METHODS AND RESULTS: Home blood pressure was measured for 14 consecutive days in 1082 patients with type 2 diabetes, and pulse pressure was calculated. A 10 mmHg increase in morning PP was associated with a 1.30-fold increase in the risk of cardiovascular disease. The risk of cardiovascular disease was 1.88 times higher in the morning in the higher PP group than in the lower PP group. In the receiver operating characteristic analysis, the areas under the curve (95% confidence interval) corresponding to the PP (morning, evening, and clinic) for new-onset cardiovascular disease were 0.63 (0.58-0.69), 0.62 (0.57-0.67), and 0.59 (0.54-0.64), respectively. The area under the curve for PP measured in the morning was significantly greater than that for PP measured in the clinic (P = 0.032). CONCLUSION: Home-measured PP is a better predictor of new-onset cardiovascular disease than clinic-measured PP, in patients with type 2 diabetes.
• The relationship between years of anesthesia experience and first-time intubation success rate with direct laryngoscope and video laryngoscope in infants: a retrospective observational study.

  Yuka Uchinami, Noriaki Fujita, Takashi Ando, Kazuyuki Mizunoya, Koji Hoshino, Isao Yokota, Yuji Morimoto

  Journal of anesthesia 2022年09月20日 

  PURPOSE: Studies in adults have reported that video laryngoscope is more useful than direct laryngoscope when training less experienced anesthesiologists. However, whether this is true for infants remains unclear. Therefore, this study aimed to evaluate whether the use of video laryngoscope would result in smaller differences in success rate according to anesthesiologists' expertise than those in direct laryngoscope. METHODS: Medical records and video recordings from the operating room of patients aged < 1 year who underwent non-cardiac surgery between March 2019 and September 2021 were reviewed. Tracheal intubations between April 8, 2020, and June 20, 2021, were excluded due to the shortage of video laryngoscope blades during the COVID-19 pandemic. Rates of first-time tracheal intubation success were compared by years of anesthesia experience and initial intubation device. RESULTS: In total, 125 of 175 tracheal intubations were analyzed (direct laryngoscope group, n = 72; video laryngoscope group, n = 53). The first-time tracheal intubation success rate increased with years of experience as an anesthesiologist in the direct laryngoscope group (odds ratio OR 1.70, 95% confidence interval CI 1.15, 2.49; P = 0.0070), but not the video laryngoscope group (OR 0.99, 95% CI 0.74, 1.35; P = 0.99). CONCLUSION: The differences in success rate according to the anesthesiologists' years of experience were non-significant when using video laryngoscope in infants, compared to those in direct laryngoscope.
• Dose-dependent relationship of blood pressure and glycemic status with risk of aortic dissection and aneurysm.

  Yuta Suzuki, Hidehiro Kaneko, Yuichiro Yano, Akira Okada, Hidetaka Itoh, Kensuke Ueno, Satoshi Matsuoka, Katsuhito Fujiu, Nobuaki Michihata, Taisuke Jo, Norifumi Takeda, Hiroyuki Morita, Isao Yokota, Koichi Node, Hideo Yasunaga, Issei Komuro

  European journal of preventive cardiology 2022年09月09日 

  AIM: Data on the dose-dependent association of blood pressure (BP) and fasting plasma glucose (FPG) level with the risk of aortic dissection (AD) and aortic aneurysm (AA) are limited. METHODS: This observational cohort study included 3,358,293 individuals registered in a health check-up and claims database in Japan (median age, 43 [36-51] years; 57.2% men). Individuals using BP- or glucose-lowering medications or those with a history of cardiovascular disease were excluded. RESULTS: In a mean follow-up period of 1,199 ± 950 days, 1,095 and 2,177 cases of AD and AA, respectively, were recorded. Compared with normal/elevated BP, HRs of stage 1 and stage 2 hypertension were 1.89 (95% CI:1.60-2.22) and 5.87 (95% CI:5.03-6.84) for AD and 1.37 (95% CI:1.23-1.52) and 2.17 (95% CI:1.95-2.42) for AA, respectively. Compared with normal FPG, HRs of prediabetes and diabetes were 0.82 (95% CI:0.71-0.94) and 0.48 (95% CI:0.33-0.71) for AD and 0.94 (95% CI:0.85-1.03) and 0.61 (95% CI:0.47-0.79) for AA, respectively. The cubic spline demonstrated that the risk of AD and AA increased with increasing BP but decreased with increasing FPG level. Contour plots using generalized additive models showed that higher SBP and lower FPG level were associated with an elevated risk of AD and AA. CONCLUSIONS: Our analysis showed a dose-dependent increase in the risk of AD or AA with BP and a similar decrease associated with FPG, and also suggested a potential interaction between hypertension and hyperglycemia in the development of AD and AA.
• Patterns of premenstrual syndrome in collegiate women: A cross-sectional study

  Saori Morino, Hinako Hirata, Daisuke Matsumoto, Isao Yokota, Tomoki Aoyama

  Medicine 101 35 e30186 - e30186 2022年09月02日
• Time of Day of Vaccination Does Not Associate With SARS-CoV-2 Antibody Titer Following First Dose of mRNA COVID-19 Vaccine.

  Yamanaka Y, Yokota I, Yasumoto A, Morishita E, Horiuchi H

  Journal of biological rhythms 2022年09月
• In Reply to the Letter to the Editor Regarding "Does Primary Tumor Resection in Patients with Metastatic Primary Mobile Vertebral Column Sarcoma Improve the Survivals?".

  Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Norimasa Iwasaki

  World neurosurgery 165 210 - 210 2022年09月
• Various factors contribute to death in patients with different types of pulmonary hypertension: A retrospective pilot study from a single tertiary center.

  Junichi Nakamura, Ichizo Tsujino, Hiroshi Ohira, Toshitaka Nakaya, Ayako Sugimoto, Takahiro Sato, Taku Watanabe, Masaru Suzuki, Masaru Kato, Isao Yokota, Satoshi Konno

  Respiratory investigation 60 5 647 - 657 2022年09月 

  BACKGROUND: A few studies have focused on the cause of death from different types of pulmonary hypertension (PH). This study aimed to systematically analyze the primary and secondary causes of death and compare the profiles between different PH groups. METHODS: The contribution of PH to death was assessed in precapillary PH (i.e., group 1 [pulmonary arterial hypertension], group 3 [PH associated with lung disease], and group 4 [chronic thromboembolic PH]) using specific criteria; death was classified into three categories: PH death (death due to PH only), PH-related death, and PH-unrelated death. Disorders other than PH that contributed to death were analyzed, and mortality profiles were compared between groups. RESULTS: Eighty deceased patients with PH were examined (group 1, n = 28; group 3, n = 39; and group 4, n = 13). The contribution of PH to death was significantly different between the three groups. "PH death" was most common in group 1 (61%), "PH-related death" in group 3 (56%), and "PH-related death" and "PH-unrelated death" in group 4 (38% for both). The highest contributing factor to death other than PH was respiratory failure in group 3 and malignant disease in group 4. CONCLUSIONS: Significant variations in the causes of death were observed in groups 1, 3, and 4 PH patients. In addition to PH, respiratory failure and malignant disease significantly contributed to death in group 3 and group 4 PH, respectively. Understanding the precise death cause may be important in achieving better outcomes in PH patients.
• Precise and comprehensive determination of multiple body fluids by applying statistical cutoff values to a multiplex reverse transcription-PCR and capillary electrophoresis procedure for forensic purposes

  Tomoko Akutsu, Isao Yokota, Ken Watanabe, Kochi Toyomane, Takayuki Yamagishi, Koichi Sakurada

  Legal Medicine 58 102087 - 102087 2022年09月
• Threshold of Body Mass Index for the Development of Hypertension Among Japanese Adults.

  Yuta Suzuki, Hidehiro Kaneko, Yuichiro Yano, Akira Okada, Yohei Hashimoto, Hidetaka Itoh, Satoshi Matsuoka, Isao Yokota, Katsuhito Fujiu, Nobuaki Michihata, Taisuke Jo, Norifumi Takeda, Hiroyuki Morita, Kentaro Kamiya, Atsuhiko Matsunaga, Junya Ako, Koichi Node, Hideo Yasunaga, Issei Komuro

  The Journal of nutrition 2022年08月30日 

  BACKGROUND: The optimal value of body mass index (BMI) for the development of hypertension and the influence of BMI on the development of stage 1 or stage 2 hypertension remain unclear. OBJECTIVES: We sought to identify the BMI threshold for the prevention of hypertension and how changes in BMI would influence the risk of developing hypertension. DESIGN AND METHODS: We analyzed 1,262,356 participants (median age;43 years;50.9% men) with normal blood pressure (BP) (systolic BP [SBP]< 120 mmHg and diastolic BP [DBP]< 80 mmHg) or elevated BP (SBP 120-129 mmHg and DBP < 80 mmHg). The primary outcome was stage 1 (SBP 130-139 mmHg or DBP 80-89 mmHg) or stage 2 hypertension (SBP ≥ 140 mmHg or DBP ≥ 90 mmHg). We analyzed the relationship between baseline BMI, change in BMI, and the risk of developing hypertension using generalized additive models with a smoothing spline. RESULTS: During the median follow-up of 851 days, 341,212 cases of stage 1 hypertension and 70,968 cases of stage 2 hypertension were detected. The risk of developing stage 1 or stage 2 hypertension increased steeply after BMI exceeded 20 kg/m2. The annual change in BMI was positively correlated with the risk of developing stage 1 or 2 hypertension. Contour mapping using generalized additive models demonstrated an additive increase in the risk of developing hypertension with higher baseline BMI and increases in BMI over one year. Body weight gain increases the risk of developing hypertension even in underweight or normal-weight individuals based on the World Health Organization classification. CONCLUSIONS: In Japanese adults with normal or elevated BP, risk of developing hypertension increased with BMI when baseline BMI was greater than 20 kg/m². Body weight gain additively interacted with baseline BMI during hypertension development. Our results underscore the importance of maintaining body weight in preventing the development of hypertension.
• Usefulness of ultrasonography and elastography in diagnosing oxaliplatin-induced sinusoidal obstruction syndrome.

  Rika Saito, Yasuyuki Kawamoto, Mutsumi Nishida, Takahito Iwai, Yasuka Kikuchi, Isao Yokota, Ryo Takagi, Takahiro Yamamura, Ken Ito, Kazuaki Harada, Satoshi Yuki, Yoshito Komatsu, Naoya Sakamoto

  International journal of clinical oncology 27 11 1780 - 1790 2022年08月30日 

  BACKGROUND: Sinusoidal obstruction syndrome (SOS) refers to liver injury caused by hematopoietic stem cell transplantation (HSCT) and anticancer drugs including oxaliplatin. Increased splenic volume (SV) on computed tomography (CT) indicates oxaliplatin-induced SOS. Similarly, ultrasonography and liver stiffness measurement (LSM) by shear-wave elastography (SWE) can help diagnose SOS after HSCT; however, their usefulness for diagnosing oxaliplatin-induced SOS remains unclear. We investigated the usefulness of the Hokkaido ultrasonography-based scoring system with 10 ultrasonographic parameters (HokUS-10) and SWE in diagnosing oxaliplatin-induced SOS early. METHODS: In this prospective observational study, ultrasonography and SWE were performed before and at 2, 4, and 6 months after oxaliplatin-based chemotherapy. HokUS-10 was used for assessment. CT volumetry of the SV was performed in clinical practice, and an SV increase ≥ 30% was considered the diagnostic indicator of oxaliplatin-induced SOS. We assessed whether HokUS-10 and SWE can lead to an early detection of oxaliplatin-induced SOS before an increased SV on CT. RESULTS: Of the 30 enrolled patients with gastrointestinal cancers, 12 (40.0%) with an SV increase  ≥ 30% on CT were diagnosed with SOS. The HokUS-10 score was not correlated with an SV increase ≥ 30% (r = 0.18). The change in rate of three HokUS-10 parameters were correlated with an SV increase ≥ 30% (r = 0.32-0.41). The change in rate of LSM by SWE was correlated with an SV increase  ≥ 30% (r = 0.40). CONCLUSIONS: The usefulness of HokUS-10 score was not demonstrated; however, some HokUS-10 parameters and SWE could be useful for the early diagnosis of oxaliplatin-induced SOS.
• Maximum home blood pressure and cardiovascular outcomes in patients with type 2 diabetes: KAMOGAWA-HBP study.

  Shinnosuke Hata, Emi Ushigome, Takashi Yoshimura, Maya Takegami, Nobuko Kitagawa, Toru Tanaka, Goji Hasegawa, Masayoshi Ohnishi, Sei Tsunoda, Isao Yokota, Hidetaka Ushigome, Mai Asano, Masahide Hamaguchi, Masahiro Yamazaki, Michiaki Fukui

  Journal of hypertension 40 12 2430 - 2437 2022年08月19日 

  OBJECTIVE: The maximum blood pressure was reported as a possible marker of organ damage. We previously showed that maximum home blood pressure was significantly associated with development of diabetic nephropathy. In the same cohort of patients with diabetes as in the previous study, this study aimed to evaluate the prognostic blood pressure values for the onset of first cardiovascular events. METHODS: This retrospective cohort study included 1082 patients with type 2 diabetes (47.0% female, median age 65.0) without a history of macrovascular complications. Blood pressure measurements were performed in triplicates every morning and evening for 14 consecutive days from the start of the study. Cox hazards model was used to evaluate the risk of primary endpoint, which was defined as the onset of first major cardiovascular event. RESULTS: The primary endpoint occurred in 119 patients (incidence rate, 15.7/1000 person-years) during an average of 7.0-year follow-up. The adjusted hazard ratios (95% confidence interval [CI]) of maximum morning systolic blood pressure (SBP) and maximum evening SBP for cardiovascular events were 1.12 (1.01-1.24) and 1.19 (1.07-1.31), respectively, adjusted by sex, duration of diabetes, body mass index, hemoglobin A1c, low density lipoprotein cholesterol, smoking status, and use of antihypertensive medications. The cutoff values of maximum blood pressure for the events were 150 mmHg in the morning (hazard ratio, 1.73; 95% CI, 1.07-2.81) and 157 mmHg in the evening (hazard ratio, 2.30; 95% CI, 1.46-3.61), using the Youden's index. CONCLUSION: Maximum home blood pressure is a predictor of subsequent cardiovascular events in patients with type 2 diabetes.
• Comparison of clinical features between patients with bone and soft tissue fibrosarcomas.

  Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Ryosuke Hishimura, Yuki Suzuki, Eiji Kondo, Norimasa Iwasaki

  Journal of surgical oncology 126 7 1299 - 1305 2022年08月08日 

  BACKGROUND AND OBJECTIVES: Fibrosarcomas predominantly arise in soft tissues, but can also develop in bone. Because of their rarity, whether bone development has an impact on clinical features has not been addressed. METHODS: We included fibrosarcoma patients diagnosed between 1983 and 2016 in the Surveillance, Epidemiology, and End Results database. Differences in clinical features between fibrosarcoma of bone (FS-B) and fibrosarcoma of soft tissue (FS-ST) were investigated. RESULTS: After excluding patients without information regarding cause of death, site of origin, distant tumor or survival, 1443 patients were included. Of those, 98 patients had FS-B. Patients with FS-B were younger, more frequently male, with fibrosarcomas that more often developed in an extremity and were histologically high-grade. In contrast, no difference in potential to metastasize was observed. Survival was almost equal between FS-B and FS-ST (FS-B/FS-ST: cancer-specific survival, hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.8-1.7; overall survival, HR: 1.3, 95% CI: 0.9-1.7). CONCLUSIONS: Our results clearly indicated that patient backgrounds differed, such as younger age and greater tendencies to affect males, develop in an extremity and show high-grade tumor in patients with FS-B. In contrast, no differences were observed in distant metastatic potential or survival.
• Potential determinants of T helper 2 markers and their distribution in school-aged children

  Houman Goudarzi, Atsuko Ikeda-Araki, Yu Ait Bamai, Sachiko Ito, Tasuku Inao, Isao Yokota, Chihiro Miyashita, Reiko Kishi, Satoshi Konno

  Allergology International 2022年08月
• Predictors of the development of nab-paclitaxel-induced peripheral neuropathy in breast cancer patients: post hoc analysis of a prospective, phase II, self-controlled clinical trial.

  Yuko Kanbayashi, Koichi Sakaguchi, Takeshi Ishikawa, Yusuke Tabuchi, Ryo Takagi, Isao Yokota, Norito Katoh, Koichi Takayama, Tetsuya Taguchi

  Medical oncology (Northwood, London, England) 39 10 153 - 153 2022年07月19日 

  In a previous study, we showed that cryotherapy and compression therapy have comparable efficacy in preventing nab-paclitaxel-induced peripheral neuropathy. However, even with cryotherapy or compression therapy, there were patients with National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 grade ≥ 2 and/or Patient Neurotoxicity Questionnaire (PNQ) grade ≥ D peripheral neuropathies. Therefore, this post hoc analysis was performed to identify predictors of nab-paclitaxel-induced peripheral neuropathy. The clinical data in this post hoc analysis were the data of 38 breast cancer patients receiving chemotherapy with nanoparticle albumin-bound paclitaxel (nab-PTX) at our outpatient chemotherapy center from August 2017 to March 2019. The number of patients was analyzed assuming that there were data for 76 hands. Variables related to the development of nab-PTX-induced peripheral neuropathy were used for regression analysis. Multivariate-ordered logistic regression analysis was performed to identify predictors for the development of nab-PTX-induced peripheral neuropathy. Significant factors included smoking history [odds ratio (OR) 4.64, 95% confidence interval (CI) 1.60-13.5; P = 0.0048] with neuropathy evaluated by CTCAE, body mass index (BMI) (OR 1.13, 95% CI 1.01-1.26; P = 0.039) with neuropathy evaluated by PNQ (sensory), and smoking history (OR 3.80, 95% CI 1.40-10.30; P = 0.0087) and age (OR 1.06, 95% CI 1.01-1.11; P = 0.012) with neuropathy evaluated by PNQ (motor). In conclusion, smoking history, BMI and age were identified as significant predictors of the development of nab-PTX-induced-peripheral neuropathy.
• Liver metastasis in soft tissue sarcoma at initial presentation.

  Yuta Kawae, Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Ryosuke Hishimura, Yuki Suzuki, Eiji Kondo, Norimasa Iwasaki

  Journal of surgical oncology 126 6 1074 - 1079 2022年07月06日 

  BACKGROUND AND OBJECTIVES: Noncontrast computed tomography of the chest is the standard imaging modality for cancer staging in patients with soft tissue sarcoma (STS), but appropriate candidates for liver screening have not been clarified. METHODS: We reviewed all patients with STS diagnosed between 2010 and 2018 in the Surveillance, Epidemiology, and End Results database. Incidence of liver metastasis at initial presentation and high incidence of liver metastasis by histological subtype were investigated. In addition, risk factors for liver metastasis were investigated by multiple logistic regression analysis. RESULTS: After excluding patients without information about liver metastasis, cause of death or primary liver tumor, 47 260 patients were included in this study. Of those, 1471 patients (3.2%) showed liver metastasis at initial presentation. The histological subtype showing the highest incidence of liver metastasis was desmoplastic small round cell tumor (30.3%), followed by malignant hemangioendothelioma (11.5%) and angiomyoliposarcoma (10.5%). Deep-rooted tumor, location in the body wall, retroperitoneum, or thorax/peritoneum, high histological grade, and higher T stage were associated with higher incidences of liver metastasis at initial presentation. CONCLUSION: Risk factors for liver metastasis were deep location, trunk development, larger tumor size, high histological grade, and specific histological subtypes.
• A study on predicting cases that would benefit from proton beam therapy in primary liver tumors of less than or equal to 5 cm based on the estimated incidence of hepatic toxicity

  Yusuke Uchinami, Norio Katoh, Ryusuke Suzuki, Takahiro Kanehira, Masaya Tamura, Seishin Takao, Taeko Matsuura, Naoki Miyamoto, Yoshihiro Fujita, Fuki Koizumi, Hiroshi Taguchi, Koichi Yasuda, Kentaro Nishioka, Isao Yokota, Keiji Kobashi, Hidefumi Aoyama

  Clinical and Translational Radiation Oncology 35 70 - 75 2022年07月 

  Background: For small primary liver tumors, favorable outcomes have been reported with both of proton beam therapy (PBT) and X-ray therapy (XRT). However, no clear criteria have been proposed in the cases for which and when of PBT or XRT has to be used. The aim of this study is to investigate cases that would benefit from PBT based on the predicted rate of hepatic toxicity. Materials and methods: Eligible patients were those who underwent PBT for primary liver tumors with a maximum diameter of ≤ 5 cm and Child-Pugh grade A (n = 40). To compare the PBT-plan, the treatment plan using volumetric modulated arc therapy was generated as the XRT-plan. The rate of predicted hepatic toxicity was estimated using five normal tissue complication probability (NTCP) models with three different endpoints. The differences in NTCP values (ΔNTCP) were calculated to determine the relative advantage of PBT. Factors predicting benefits of PBT were analyzed by logistic regression analysis. Results: From the dose-volume histogram comparisons, an advantage of PBT was found in sparing of the normal liver receiving low doses. The factors predicting the benefit of PBT differed depending on the selected NTCP model. From the five models, the total tumor diameter (sum of the target tumors), location (hepatic hilum vs other), and number of tumors (1 vs 2) were significant factors. Conclusions: From the radiation-related hepatic toxicity, factors were identified to predict benefits of PBT in primary liver tumors with Child-Pugh grade A, with the maximum tumor diameter of ≤ 5 cm.
• The agreement between measured HbA1c and optimized target HbA1c based on the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8): A cross-sectional study of elderly patients with diabetes.

  Aika Miya, Akinobu Nakamura, Isao Yokota, Kyu Yong Cho, Hiraku Kameda, Hiroshi Nomoto, Takahiro Takase, Kazuno Omori, Mayuko Ono, So Nagai, Shinji Taneda, Hideaki Miyoshi, Tatsuya Atsumi

  Geriatrics & gerontology international 22 8 560 - 567 2022年06月30日 

  AIM: To investigate the achievement of individualized target HbA1c based on the Japanese guideline after geriatric assessment with the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) and to evaluate patient characteristics acting as barriers to achieving the target HbA1c in elderly outpatients with diabetes. METHODS: This cross-sectional study enrolled 303 Japanese outpatients aged ≥65 years with diabetes. Their health status was measured using the DASC-8. The target HbA1c was optimized for each patient by the guideline based on the DASC-8 score and use of drugs potentially associated with severe hypoglycemia. Patient characteristics related to the agreement between measured HbA1c and target HbA1c were extracted by multivariate logistic regression analysis. RESULTS: The mean age was 73.0 years and the mean body mass index (BMI) was 24.2 kg/m2 . The agreement between measured HbA1c and target HbA1c was 43.9% (95% confidence interval: 38.4%-50.0%). In multivariate logistic regression analysis, the agreement in patients with drugs potentially associated with severe hypoglycemia was significantly lower than in those without these drugs (37.8% vs. 60.5%, P = 0.0004). In patients with these drugs, higher BMI (P = 0.0271) and higher fasting plasma glucose (P = 0.0034) were independent related factors for measured HbA1c being higher than target HbA1c. Vulnerable elderly patients (P = 0.0116) and not taking sodium glucose co-transporter-2 (SGLT2) inhibitor (P = 0.0186) were independent related factors for inappropriately lower HbA1c. CONCLUSIONS: The agreement between measured HbA1c and target HbA1c was low in elderly patients with diabetes. Geriatr Gerontol Int 2022; ••: ••-••.
• The renoprotective effect of once-weekly GLP-1 receptor agonist dulaglutide on progression of nephropathy in Japanese patients with type 2 diabetes and moderate to severe chronic kidney disease (JDDM67).

  Ken-Ichi Tsuchida, Shinji Taneda, Isao Yokota, Kazufumi Okada, Yoshio Kurihara, Hiroki Yokoyama, Masahiro Iwamoto, Katsuya Yamazaki, Yasushi Ishigaki, Naoki Manda, Hiroshi Maegawa

  Journal of diabetes investigation 13 11 1834 - 1841 2022年06月23日 

  AIMS/INTRODUCTION: Few studies have investigated the renoprotective effect of glucagon-like peptide-1 (GLP-1) receptor in patients with chronic kidney disease (CKD). This study evaluated the effect of dulaglutide 0.75 mg on renal function in Japanese patients with type 2 diabetes and CKD stage 3 to 4. MATERIALS AND METHODS: Dulaglutide (group A) and non-dulaglutide (group B) were compared using data collected from a computerized diabetes care database. For group B, propensity score weighting based on propensity scores was performed. Evaluation items were a change from baseline in hemoglobin A1c (HbA1c), body weight, urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), for 3 years. RESULTS: In total, the data obtained from 255 patients (125 and 130 patients for group A and B, respectively) were analyzed. Propensity score-adjusted patient background characteristics (group A vs B) were age 70.8 vs 69.4 years, body weight 70.2 vs 72.9 kg, body mass index 27.3 vs 28.1 kg/m2 , HbA1c 8.4 vs 8.5%, eGFR 47.9 vs 47.7 mL/min/1.73 m2 , and UACR 218 vs 251 mg/gCr. Although there were no statistically significant differences in the change from baseline between groups A and B at most time points in eGFR, a statistically significant eGFR decline in group B was observed in slope analysis for 3 years. This renoprotective effect was marked in patients with macro-albuminuria and/or concomitant SGLT2 inhibitor use. CONCLUSIONS: Dulaglutide slowed the eGFR decline in patients with type 2 diabetes and CKD stage 3 to 4.
• Precise and comprehensive determination of multiple body fluids by applying statistical cutoff values to a multiplex reverse transcription-PCR and capillary electrophoresis procedure for forensic purposes.

  Tomoko Akutsu, Isao Yokota, Ken Watanabe, Kochi Toyomane, Takayuki Yamagishi, Koichi Sakurada

  Legal medicine (Tokyo, Japan) 58 102087 - 102087 2022年05月14日 

  Body fluid identification from crime scene evidence is an essential procedure in forensic investigations. Among various procedures, multiplex reverse transcription PCR assays have a clear advantage over conventional methods because different types of body fluids can be analyzed simultaneously. For more precise, comprehensive, and objective identification of forensically relevant body fluids, 15 target genes for blood, saliva, semen, vaginal fluid, and nasal secretion were selected; their primers were re-designed and multiplex PCR conditions were optimized to prioritize specificity for those body fluids. Multiple amplicons were separated and determined by the SeqStudio Genetic Analyzer with an all-in-one and easy-to-use cartridge. Then, the cutoff value was set for each marker to eliminate the detection of slight amplification in non-targeted body fluids. As a result, the targeted body fluid specificities of the developed procedure were drastically improved. Although successful determination of the target gene depends on sample condition and marker sensitivity, our procedure was applicable for the precise determination of body fluids in mixed body fluid stains, aged samples, and various mock casework samples. Therefore, it could be a powerful and convenient tool for the precise identification of multiple body fluids in forensic laboratories.
• Study protocol of the HGCSG1803: a phase II multicentre, non-randomised, single-arm, prospective trial of combination chemotherapy with oxaliplatin, irinotecan and S-1 (OX-IRIS) as first-line treatment for metastatic or relapsed pancreatic cancer.

  Shintaro Nakano, Yasuyuki Kawamoto, Satoshi Yuki, Kazuaki Harada, Takuto Miyagishima, Susumu Sogabe, Masayoshi Dazai, Atsushi Sato, Atsushi Ishiguro, Michio Nakamura, Shinya Kajiura, Yasuo Takahashi, Miki Tateyama, Kazuteru Hatanaka, Yasushi Tsuji, Takahide Sasaki, Yoshiaki Shindo, Tomoe Kobayashi, Isao Yokota, Naoya Sakamoto, Yuh Sakata, Yoshito Komatsu

  BMJ open 12 5 e048833  2022年05月09日 

  INTRODUCTION: Combination chemotherapy with oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) has become one of the standard treatments for metastatic pancreatic cancer. However, the use of FOLFIRINOX requires prolonged infusion. Therefore, we planned to develop a new combination chemotherapy regimen with oxaliplatin, irinotecan and S-1 (OX-IRIS) for advanced pancreatic cancer. In the phase Ⅰ study that was conducted previously, the safety and recommended dose of OX-IRIS were assessed. In this study, we will evaluate the efficacy and safety of OX-IRIS. METHODS AND ANALYSIS: The HGCSG1803 study started as a multicentre, non-randomised, single-arm, prospective, phase II study in December 2019. Eligible subjects were patients with untreated metastatic or relapsed pancreatic cancer. OX-IRIS is administered as follows: 30 min infusion of antiemetic; 2-hour infusion of oxaliplatin (65 mg/m2); 1.5-hour infusion of irinotecan (100 mg/m2) on day 1 and 15 of each 4-week cycle; and oral S-1 (40 mg/m2) twice daily from after dinner on day one to after breakfast on day 15, followed by a 14-day rest, to be repeated every 2 weeks until disease progression, unacceptable toxicity or patient refusal. The primary endpoint is response rate. The secondary endpoints are overall and progression-free survival, safety and dose for each drug. Using a binomial test, a sample size of 40 patients was set with a threshold value of 10% and expected value of 30%. Registration of 40 cases is planned from 18 institutions in Japan. ETHICS AND DISSEMINATION: All the procedures will be conducted in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Declaration of Helsinki of 1964 and its later versions. All the patients will receive written information about the trial and will provide informed consent before enrolment. This trial was approved by the Hokkaido University Certified Review Board (approval No: 018-037). TRIAL REGISTRATION NUMBER: jRCTs011190008.
• Intraoperative factors influencing transcranial motor-evoked potential measurements using higher frequency multi-train stimulation in adolescent scoliosis surgery: A prospective observational study

  Toki T, Fujita N, Ichikawa T, Ochi N, Yokota I, Sudo H, Morimoto Y

  2022年05月
• Diabetic nephropathy ameliorated in patients with normal home blood pressure compared to those with isolated high home systolic blood pressure: A 5-year prospective cohort study among patients with type 2 diabetes mellitus.

  Kitagawa N, Ushigome E, Kitagawa N, Ushigome H, Yokota I, Nakanishi N, Hamaguchi M, Asano M, Yamazaki M, Fukui M

  Diabetes & vascular disease research 2022年05月
• Usefulness of Exercise for Home Blood Pressure Control in People with Diabetes: A Study Protocol for a Crossover Randomized Controlled Trial [Corrigendum]

  Keiko Iwai, Emi Ushigome, Isao Yokota, Saori Majima, Naoko Nakanishi, Yoshitaka Hashimoto, Hiroshi Okada, Takafumi Senmaru, Masahide Hamaguchi, Mai Asano, Masahiro Yamazaki, Michiaki Fukui

  Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy Volume 15 1525 - 1526 2022年05月
• Does Primary Tumor Resection in Patients with Metastatic Primary Mobile Vertebral Column Sarcoma Improve Survival?

  Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Ryosuke Hishimura, Yuki Suzuki, Akira Iwata, Eiji Kondo, Norimasa Iwasaki

  World neurosurgery 163 e647-e654  2022年04月18日 

  BACKGROUND: Primary mobile vertebral column sarcoma is an exceedingly rare malignancy. Although primary tumor resection has been reported to prolong survival in patients with metastatic bone sarcoma, whether primary tumor resection in patients with advanced primary mobile vertebral column sarcoma is associated with survival remains unclear owing to the rarity of this pathological entity. METHODS: Using the Surveillance, Epidemiology, and End Results database, 182 patients with metastatic primary mobile vertebral column sarcoma were identified between 1983 and 2015. Of the 182 patients enrolled, 101 patients (55%) underwent primary tumor resection (Surgery group) and 81 patients (45%) did not undergo resection (No Surgery group). To account for imbalances in the basic characteristics of patients between groups, propensity score matching was performed. Survival analysis was performed by weighted Cox proportional hazards modeling to calculate hazard ratios. RESULTS: After adjusting for patient background characteristics, 138 patients were included for the analysis (Surgery group: 69 patients; No Surgery group: 69 patients). The Surgery group did not show improved cancer-specific survival (hazard ratio = 0.73, 95% CI 0.49-1.10). Similarly, the Surgery group did not show improved overall survival compared with the No Surgery group (hazard ratio = 0.80, 95% CI 0.55-1.16). CONCLUSIONS: To our knowledge, this is the first study to indicate that surgical resection for advanced primary mobile vertebral column sarcoma does not have a positive impact on survival.
• 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 

  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.
• Analysis of the Pancreatic Cancer Microbiome Using Endoscopic Ultrasound-Guided Fine-Needle Aspiration-Derived Samples.

  Shintaro Nakano, Yasuyuki Kawamoto, Yoshito Komatsu, Rika Saito, Ken Ito, Takahiro Yamamura, Kazuaki Harada, Satoshi Yuki, Kazumichi Kawakubo, Ryo Sugiura, Shin Kato, Koji Hirata, Hajime Hirata, Masahito Nakajima, Ryutaro Furukawa, Yunosuke Takishin, Kousuke Nagai, Isao Yokota, Keisuke H Ota, Shinji Nakaoka, Masaki Kuwatani, Naoya Sakamoto

  Pancreas 51 4 351 - 357 2022年04月01日 

  OBJECTIVES: Most previous studies have analyzed bacteria in tumors using resected pancreatic cancer (PC) tissues, because it is difficult to obtain tissue samples from unresectable advanced PC. We aimed to determine whether minimal tissue obtained by endoscopic ultrasound-guided fine-needle aspiration is useful for microbiome analysis. METHODS: Thirty PC and matched duodenal and stomach tissues (N = 90) were prospectively collected from 30 patients who underwent endoscopic ultrasound-guided fine-needle aspiration. Bacterial DNA was extracted, and 16S rRNA sequencing was performed. The primary outcome was the success rate of bacterial detection in tumors. Bacterial diversity and structure were investigated. RESULTS: The bacterial detection rates were 80%, 100%, and 97% in PC, gastric, and duodenal samples, respectively. Pancreatic cancer tissues showed a lower α-diversity and a significantly different microbial structure than stomach and duodenal tissues. Proteobacteria were more abundant, whereas Firmicutes, Bacteroidetes, and Fusobacteria were less abundant in PC tissues than in stomach and duodenal tissues. Acinetobacter was more abundant in PC tissues than in stomach and duodenal tissues, and Delftia was more frequently detected in resectable PC. CONCLUSIONS: Endoscopic ultrasound-guided fine-needle aspiration samples were valuable for PC microbiome analysis, revealing that the bacterial composition of PC is different from that of the stomach and duodenum.
• Accuracy of Swan‒Ganz catheterization-based assessment of right ventricular function: Validation study using high-fidelity micromanometry-derived values as reference.

  Hideki Shima, Toshitaka Nakaya, Ichizo Tsujino, Junichi Nakamura, Ayako Sugimoto, Takahiro Sato, Taku Watanabe, Hiroshi Ohira, Masaru Suzuki, Masaru Kato, Isao Yokota, Satoshi Konno

  Pulmonary circulation 12 2 e12078  2022年04月 

  Right ventricular (RV) function critically affects the outcomes of patients with pulmonary hypertension (PH). Pressure wave analysis using Swan‒Ganz catheterization (SG-cath) allows for the calculation of indices of RV function. However, the accuracy of these indices has not been validated. In the present study, we calculated indices of systolic and diastolic RV functions using SG-cath-derived pressure recordings in patients with suspected or confirmed PH. We analyzed and validated the accuracies of three RV indices having proven prognostic values, that is, end-systolic elastance (Ees)/arterial elastance (Ea), β (stiffness constant), and end-diastolic elastance (Eed), using high-fidelity micromanometry-derived data as reference. We analyzed 73 participants who underwent SG-cath for the diagnosis or evaluation of PH. In this study, Ees/Ea was calculated via the single-beat pressure method using [1.65 × (mean pulmonary arterial pressure) - 7.79] as end-systolic pressure. SG-cath-derived Ees/Ea, β, and Eed were 0.89 ± 0.69 (mean ± standard deviation), 0.027 ± 0.002, and 0.16 ± 0.02 mmHg/ml, respectively. The mean differences (limits of agreement) between SG-cath and micromanometry-derived data were 0.13 (0.99, -0.72), 0.002 (0.020, -0.013), and 0.04 (0.20, -0.12) for Ees/Ea, β, and Eed, respectively. The intraclass correlation coefficients of the indices derived from the two catheterizations were 0.76, 0.71, and 0.57 for Ees/Ea, β, and Eed, respectively. In patients with confirmed or suspected PH, SG-cath-derived RV indices, especially Ees/Ea and β, exhibited a good correlation with micromanometry-derived reference values.
• Antibody responses induced by the BNT162b2 mRNA COVID-19 vaccine in healthcare workers in a single community hospital in Japan.

  Shinya Otsuka, Kei Hiraoka, Masato Suzuoki, Hideki Ujiie, Tatsuya Kato, Isao Yokota, Kazuya Yonezawa, Keiji Oguma, Nozomu Iwashiro, Mototsugu Kato, Masanori Ohara

  Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 28 4 539 - 542 2022年04月 

  INTRODUCTION: The effectiveness of several vaccines against coronavirus disease (COVID-19) has been reported in the real-world setting. However, it is still unknown how long antibodies persist following vaccination and whether or not the persistence of antibodies has a protective effect against COVID-19. METHODS: Healthcare workers who had received two doses of the BNT162b2 mRNA COVID-19 vaccine were enrolled, and a single-center study was conducted at the National Hospital Organization Hakodate National Hospital. Serum samples from all participants were collected 13-21 weeks (median: 20 weeks) after the second dose of vaccination. The antibody titers were measured using an electrochemiluminescence immunoassay (Elecsys® Anti-SARS-CoV-2 S). Data on characteristics of the participants were gathered from patient records and interview sheets. RESULTS: A total of 401 participants, among whom 70.1% were women and the median age was 42 years, were evaluated in this study. None of the participants had a definite COVID-19 history, and all participants who received complete vaccination showed positive antibody titers. The antibody titer was observed to be higher in participants with younger age (p < 0.001) and those who were females (p = 0.028). Despite the higher risk of infection than that of the general public, no vaccinated staff developed breakthrough infections. CONCLUSIONS: This study demonstrates the significant contribution of the BNT162b2 vaccine in the acquisition of anti-SARS-CoV-2S antibodies; therefore, the general population should benefit from these two vaccine doses, which are expected to be protective for at least five months.
• Multicenter, prospective, observational study of chemotherapy-induced dysgeusia in gastrointestinal cancer.

  Ken Ito, Satoshi Yuki, Hiroshi Nakatsumi, Yasuyuki Kawamoto, Kazuaki Harada, Shintaro Nakano, Rika Saito, Takayuki Ando, Kentaro Sawada, Masataka Yagisawa, Atsushi Ishiguro, Masayoshi Dazai, Ichiro Iwanaga, Kazuteru Hatanaka, Atsushi Sato, Ryusuke Matsumoto, Yoshiaki Shindo, Miki Tateyama, Tetsuhito Muranaka, Masaki Katagiri, Isao Yokota, Yuh Sakata, Naoya Sakamoto, Yoshito Komatsu

  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 30 6 5351 - 5359 2022年03月15日 

  PURPOSE: Dysgeusia is an adverse event caused by chemotherapy. Although retrospective studies have shown zinc administration improves dysgeusia, there have been no prospective studies. The present study examined effects of zinc therapy on dysgeusia in patients with gastrointestinal cancer. METHODS: This multicenter, prospective, observational study enrolled patients with dysgeusia during chemotherapy treatment. Patients received no intervention (control), polaprezinc p.o., or zinc acetate hydrate p.o., and serum zinc levels were measured at 0 (baseline), 6, and 12 weeks. Dysgeusia was assessed using CTCAE v5.0 and subjective total taste acuity (STTA) criteria using questionnaires at baseline and 12 weeks. RESULTS: From February 2020 to June 2021, 180 patients were enrolled from 17 institutes. There were no differences in mean baseline serum zinc levels among the groups (67.3, 66.6, and 67.5 μg/dL in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. P = 0.846). The changes in mean serum zinc levels after 12 weeks were - 3.8, + 14.3, and + 46.6 μg/dL, and the efficacy rates of dysgeusia were 33.3%, 36.8%, and 34.6% using CTCAE and 33.3%, 52.6%, 32.7% using STTA in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. The STTA scores improved in all groups, with significant improvement observed in the polaprezinc group compared with the no intervention group (P = 0.045). CONCLUSION: There was no significant correlation between the degree of serum zinc elevation and improvement in dysgeusia, suggesting that polaprezinc, but not zinc acetate hydrate, was effective in improving chemotherapy-induced dysgeusia. TRIAL REGISTRATION: UMIN000039653. Date of registration: March 2, 2020.
• Primary Malignant Osseous Neoplasms in the Hand.

  Shota Ike, Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Ryosuke Hishimura, Yuki Suzuki, Eiji Kondo, Norimasa Iwasaki

  Anticancer research 42 3 1635 - 1640 2022年03月 

  BACKGROUND: Primary malignant osseous neoplasms of the hand are rare malignancies. Comprehensive demographic and survival data regarding primary malignant osseous neoplasms of the hand are lacking in the literature. PATIENTS AND METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified all patients with primary malignant osseous neoplasms of the hand diagnosed between 1983 and 2015. Demographic data were searched for primary osseous neoplasms in the hand and higher incidence of histological subtype. RESULTS: A total of 197 patients were analyzed: 103 patients were diagnosed with histologically low-grade tumor, and 31 were diagnosed with high-grade tumor. Five-year cancer-specific and overall survival rates for the entire cohort were 91.4% and 81.9%, respectively. Histological high tumor grade and regional stage from SEER historic stage data were associated with unfavorable cancer-specific survival. CONCLUSION: Special caution is required if patients have histologically high-grade tumor or tumor extending beyond the periosteum into surrounding joints, as these features worsen cancer-specific mortality.
• Usefulness of Aerobic Exercise for Home Blood Pressure Control in Patients with Diabetes: Randomized Crossover Trial.

  Keiko Iwai, Emi Ushigome, Kazufumi Okada, Isao Yokota, Saori Majima, Naoko Nakanishi, Yoshitaka Hashimoto, Hiroshi Okada, Takafumi Senmaru, Masahide Hamaguchi, Mai Asano, Masahiro Yamazaki, Michiaki Fukui

  Journal of clinical medicine 11 3 2022年01月27日 

  Hypertension usually coexists with diabetes mellitus and significantly increases the risk of macrovascular complications. Blood pressure measured at home, especially nocturnal blood pressure, is particularly important because it is more strongly associated with target organ damage than clinical blood pressure measurements. Regular moderate aerobic exercise has been shown to have anti-hypertensive effects. This study aimed to investigate the effects of aerobic exercise on home blood pressure in patients with diabetes. This randomized crossover trial was based on outpatient treatment at a university hospital. In this randomized crossover trial, 124 patients with type 2 diabetes were randomly assigned to two groups over 56 days: an exercise preceding group (exercise intervention for 28 days and then no exercise intervention for the following 28 days) and an exercise lagging group (no exercise intervention for 28 days and then exercise intervention for the following 28 days). The associations between the nocturnal blood pressure and exercise intervention were assessed accordingly. A decrease in blood pressure was observed in the morning and evening, at 2 a.m. and 3 a.m. after exercise intervention; however, there was no significant difference between groups. Moderate exercise was not effective in lowering nocturnal blood pressure in this study.
• Transabdominal Ultrasonography for Preoperative Diagnosis of Lymph Node Metastasis in Colon Cancer: A Retrospective Cohort Study.

  Ken Imaizumi, Shigenori Homma, Mutsumi Nishida, Takeshi Soyama, Ryosuke Shimura, Yusuke Kudo, Satomi Omotehara, Isao Yokota, Ryo Takagi, Hiroki Matsui, Yoichi Miyaoka, Nobuki Ichikawa, Tadashi Yoshida, Norihiko Takahashi, Akinobu Taketomi

  Cancer diagnosis & prognosis 2 2 173 - 183 2022年 

  BACKGROUND/AIM: Although computed tomography (CT) is the standard modality for diagnosing lymph node metastasis (LNM), transabdominal ultrasonography (US) can be useful due to its high spatial resolution and use of Doppler signals to precisely analyse lymph nodes. This study aimed to evaluate the accuracy of US for lymph node assessment, establish US-based diagnostic criteria for LNM, and compare the capability of US with that of CT for the diagnosis of LNM. PATIENTS AND METHODS: This retrospective, single-institution, cohort study included patients who underwent radical surgery for clinical stage 0-III colon cancer, between March 2012 and February 2019. RESULTS: Overall, 34.9% (66/189) of patients had pathological LNM. The optimal US diagnostic criteria were 1) short axis ≥7 mm and short/long ratio ≥0.75 and 2) at least two of the following: the absence of hilar echoes, expansive appearance, or peripheral/mixed vascularity by the colour Doppler and/or contrast-enhanced method. Compared to CT, US showed a higher diagnostic sensitivity (54.5% vs. 43.9%; p=0.296), higher concordance with the number of pathological LNM (correlation coefficient: US, 0.42; CT, 0.27) and pathological N diagnosis (weighted ĸ: US, 0.35; CT, 0.18), and higher sensitivity for advanced LNM, including multiple LNMs (47.4% vs. 18.4%; p=0.014) and N2 stage (27.8% vs. 5.6%; p=0.177). CONCLUSION: US has higher sensitivity than CT for diagnosing LNM in colon cancer, along with a more accurate preoperative diagnosis of the N stage. Additionally, US may be more helpful than CT alone for preoperatively deciding the appropriateness of neoadjuvant treatment in colon cancer with advanced LNM.
• Association between cerebrovasoreactivity and stroke in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

  Mao Mukai, Ai Hamano, Ikuko Mizuta, Isao Yokota, Akiko Watanabe-Hosomi, Hiraku Matsuura, Takashi Koizumi, Jun Matsuura, Tomoyuki Ohara, Shigenori Matsushima, Satoshi Teramukai, Kei Yamada, Toshiki Mizuno

  Frontiers in neurology 13 1087220 - 1087220 2022年 

  BACKGROUND: Impaired cerebrovasoreactivity is thought to play an important role in the pathophysiology of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). We aimed to clarify the association between cerebrovascular reactivity and stroke in patients with CADASIL. METHODS: We retrospectively recruited 14 patients with CADASIL, eight of whom had symptomatic stroke. They underwent quantitative single-photon emission computed tomography using an autoradiographic method at rest and after acetazolamide (ACZ) administration. Regional cerebral blood flow (rCBF) in the cerebral cortex, lenticular nucleus, thalamus, and cerebellum was measured. We compared the rCBF parameters between patients with and without stroke. RESULTS: The baseline characteristics and magnetic resonance imaging findings were similar between the two groups, except for a higher frequency of pyramidal tract sign (75% vs. 0%) and a larger number of old lacunes (15.4 ± 8.8 vs. 2.2 ± 1.8) in the patients with stroke. Of the rCBF parameters measured, significantly lower flow (mL/100 g/min) was observed in ACZ-rCBF in the thalamus (35.6 ± 9.4 vs. 51.1 ± 7.6, p = 0.01) and ΔrCBF in the thalamus (10.6 ± 3.7 vs. 21.0 ± 7.9, p = 0.02) in the patients with stroke. CONCLUSION: Cerebrovasoreactivity in the thalamus was significantly associated with stroke in patients with CADASIL.
• Impact of citrus fruit intake on the mental health of patients with chronic heart failure.

  Naoya Kakutani, Takashi Yokota, Arata Fukushima, Yoshikuni Obata, Taisuke Ono, Takeshi Sota, Yoshiharu Kinugasa, Masashige Takahashi, Hisashi Matsuo, Ryuichi Matsukawa, Ichiro Yoshida, Shigeo Kakinoki, Kazuya Yonezawa, Yoshihiro Himura, Isao Yokota, Kazuhiro Yamamoto, Miyuki Tsuchihashi-Makaya, Shintaro Kinugawa

  Journal of cardiology 79 6 719 - 726 2021年12月23日 

  BACKGROUND: The full impact of the intake of citrus fruits on the risk of depression in individuals with chronic heart failure (HF) is unknown. Here, we examined the associations between the estimated habitual intakes of citrus fruits and depressive symptoms in patients with chronic HF. METHODS: We enrolled 150 stable outpatients with chronic HF who had a history of worsening HF. To assess the patients' daily dietary patterns, we used a brief self-administered diet-history questionnaire to calculate the daily consumption of foods and nutrients. To assess the patients' mental state, we used a nine-item Patient Health Questionnaire (PHQ-9). RESULTS: Twelve patients (8%) were identified as having moderate-to-severe depression (PHQ-9 score ≥10). The patients with PHQ-9 ≥10 had lower daily intakes of citrus fruits compared to those with no or mild depressive symptoms (PHQ-9 <10). The daily intakes of various antioxidants, including vitamin C, β-carotene, and β-cryptoxanthin, all of which are abundant in citrus fruits, were reduced in the patients with PHQ-9 ≥10, accompanied by higher serum levels of 8-isoprostane (an oxidative stress marker). A multivariate logistic regression analysis using forward selection showed that a lowered daily intake of citrus fruits was an independent predictor of the comorbidity of moderate-to-severe depression in patients with chronic HF, after adjustment for age, gender, and the hemoglobin value. CONCLUSIONS: A lower daily consumption of citrus fruits was associated with higher prevalence of depression in patients with chronic HF. Our findings support the hypothesis that a daily consumption of citrus fruits has a beneficial effect on the prevention and treatment of depression in chronic HF patients.
• Reply to Iwata and Yoshimura, and Endo.

  Yokota I, Sakamaki K, Shane PY, Teshima T

  Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 2021年12月
• Surgical resection of primary tumor in the extremities improves survival for metastatic soft-tissue sarcoma patients: a population-based study of the SEER database.

  M Matsuoka, T Onodera, I Yokota, K Iwasaki, S Matsubara, R Hishimura, E Kondo, N Iwasaki

  Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico 23 12 2474 - 2481 2021年12月 

  PURPOSE: The objectives of this study were to clarify whether resection of primary tumor in the extremities for patients with metastatic soft-tissue sarcoma (STS) improves survival, and to clarify patient groups for whom primary tumor resection should be considered. METHODS/PATIENTS: Using the surveillance, epidemiology, and end results database, we identified 1453 patients with metastatic STS of the extremities at initial presentation between 1983 and 2016. Of these 1453 patients, 898 patients underwent primary tumor resection (Surgery group), and 555 patients did not (No-surgery group). RESULTS: After adjusting for patient background by propensity score matching, a total of 804 patients were included for analysis. Patients in the Surgery group showed improved survival (cancer-specific survival (CSS) hazard ratio (HR) = 0.59, 95% confidence interval (CI) 0.50-0.71 overall survival rate (OS) HR = 0.60, 95% CI 0.51-0.70). In subclass analysis, patients with high-grade STS, undifferentiated pleomorphic sarcoma, leiomyosarcoma, or synovial sarcoma showed improved survival in the Surgery group (high grade-CSS HR = 0.57, 95% CI 0.45-0.72, OS HR = 0.58, 95% CI 0.48-0.71; undifferentiated pleomorphic sarcoma-CSS HR = 0.60, 95% CI 0.42-0.84, OS HR = 0.61, 95% CI 0.46-0.82; leiomyosarcoma-CSS HR = 0.50, 95% CI 0.33-0.75, OS HR = 0.50, 95% CI 0.35-0.72; synovial sarcoma-CSS HR = 0.46, 95% CI 0.31-0.68, OS HR = 0.43, 95% CI 0.30-0.62). CONCLUSIONS: Our results indicated that primary tumor resection in metastatic STS exerts positive impacts on survival. Further clinical research is needed to confirm these results.
• Variations and natural history of primary intraparenchymal lesions associated with neurofibromatosis type 2.

  Yukitomo Ishi, Taisuke Harada, Hiroyuki Kameda, Hiromi Okada, Isao Yokota, Michinari Okamoto, Ryosuke Sawaya, Hiroaki Motegi, Shigeru Yamaguchi, Shunsuke Terasaka, Kohsuke Kudo, Miki Fujimura

  Neuroradiology 64 2 393 - 396 2021年11月23日 

  The study aimed to investigate the clinical implications and natural history of primary intraparenchymal lesions in patients with neurofibromatosis type 2. Radiological findings of 15 neurofibromatosis type 2 cases were retrospectively collected. Twenty-seven primary intraparenchymal lesions were observed in 7 out of 15 patients (47%). Cortical/subcortical T2 hyperintense lesions and enlarged Virchow-Robin spaces were the most common findings in five and four patients, respectively. During the follow-up period (median 84 months), one new primary intraparenchymal lesion was identified and increased lesions were observed in two cases on contrast-enhanced MRI. Surgical resection was performed in one case pathologically diagnosed with atypical meningioma. Twenty-five other lesions without contrast enhancement presented no apparent growth during follow-up. Although most primary intraparenchymal lesions are benign, a subset of cases would present newly developed or increased lesions on contrast-enhanced MRI. Careful monitoring is necessary for such cases, and pathological confirmation should be considered.
• Electrical Storm as an Independent Mortality Risk in Patients with Preserved or Moderately Reduced Left Ventricular Function.

  Masaya Watanabe, Hisashi Yokoshiki, Takashi Noda, Isao Yokota, Takashi Nitta, Yoshifusa Aizawa, Tohru Ohe, Takashi Kurita

  International heart journal 62 6 1249 - 1256 2021年11月17日 

  Electrical storm (ES), defined by 3 or more occurrences of ventricular arrhythmias within 24 hours, has been shown to be associated with an increased risk of mortality; however, detailed information remains lacking. We aimed to examine the incidence and determinants of ES and its impact on mortality in patients enrolled in the nationwide implantable cardioverter-defibrillator (ICD) registry.We studied 1,256 patients (age 65 ± 12 years) who had structural heart disease with an ICD. The patients were classified into reduced ejection fraction (EF < 35%; 657 (52%) patients) and preserved or moderately reduced EF (EF ≥ 35%; 599 (48%) patients).ES occurred in 49 (7%) and 36 (6%) patients in the EF < 35% and EF ≥ 35% groups (log-rank P = 0.297) during the median follow-up of 2.3 years. ICD with resynchronization therapy was associated with a lower incidence of ES in patients with EF < 35%. Non-ischemic heart disease and diuretics were associated with ES in patients with EF ≥ 35%. During the follow-up, 10/49 (20%) patients with ES and 80/608 patients (13%) without ES died in patients with EF < 35%, while 7/36 (19%) patients with ES and 38/563 patients (7%) without ES died in those with EF ≥ 35%. We have created 4 Cox multivariate models. All models showed approximately 2-fold higher hazard ratios in patients with EF ≥ 35% compared to EF < 35%.Our study showed that the determinants of ES differed between EF < 35% and EF ≥ 35%. The impact of ES for mortality was numerically higher in EF ≥ 35% than in EF < 35%, although a significant interaction was not detected.
• Prediction of the intolerance or non-responder to Janus kinase inhibitors in patients with rheumatoid arthritis: a preliminary retrospective study with integrative cluster analysis.

  Masanari Sugawara, Yuichiro Fujieda, Atsushi Noguchi, Shun Tanimura, Yuka Shimizu, Ikuma Nakagawa, Masaru Yoshimura, Nobuya Abe, Michihito Kono, Masaru Kato, Kenji Oku, Olga Amengual, Isao Yokota, Hiroki Takahashi, Tatsuya Atsumi

  Clinical and experimental rheumatology 2021年11月03日 

  OBJECTIVES: To identify the subpopulation of rheumatoid arthritis (RA) non-responders to Janus kinase inhibitors (JAKis) using cluster analysis. METHODS: This retrospective study enrolled RA patients who had been treated with JAKis (tofacitinib or baricitinib) between July 2013 and September 2019 in six centres. The endpoint was set as inadequate response to JAKis (JAKis-IR), defined as either non-response to JAKis or their intolerance. Non-response to JAKis was defined as achieving neither American College of Rheumatology 20% response nor Disease Activity Score (ΔDAS28-CRP) >1.2 at 12 weeks. Withdrawal time point included earlier than after 12 weeks from baseline. A hierarchical cluster analysis was performed with variables related with clinical and serological parameters at baseline. RESULTS: The 132 RA patients enrolled were classified into four groups (Group A-D). Groups consisted of three components defined at baseline, as seropositivity, advanced joint destruction, interstitial lung disease presumably associated with RA (RA-ILD). Group A (n=32): seronegative, presence of advanced joint destruction, absence of RA-ILD. Group B (n=35): seropositive, absence of advanced joint destruction and RA-ILD. Group C (n=20): seropositive, absence of advanced joint destruction, presence of RA-ILD. Group D (n=45): seropositive, presence of advanced joint destruction and RA-ILD. The rate of JAKis-IR in four groups was as follows: A, 34.3%; B, 17.1%; C, 20.0%; and D, 8.9%. The difference in JAKis-IR rate between group A and D was statistically significant. CONCLUSIONS: A subpopulation of RA patients with a combination of the following three components, seronegativity, advanced joint destruction and absence of RA-ILD, was identified as being prone to JAKis-IR.
• Brain Metastasis in Soft Tissue Sarcoma at Initial Presentation.

  Ryo Itoga, Masatake Matsuoka, Tomohiro Onodera, Isao Yokota, Koji Iwasaki, Shinji Matsubara, Ryosuke Hishimura, Yuki Suzuki, Akira Iwata, Eiji Kondo, Norimasa Iwasaki

  Anticancer research 41 11 5611 - 5616 2021年11月 

  BACKGROUND/AIM: Brain metastasis is a rare condition among patients with soft tissue sarcoma (STS), and its precise incidence remains unclear. The aim of this study was to investigate which patients should be screened for brain metastasis. PATIENTS AND METHODS: We identified all patients with STS diagnosed between 2010 and 2015 in the SEER database. Incidence of brain metastasis at initial presentation and higher incidence of brain metastasis by histological subtype were investigated. In addition, risk factors for brain metastasis were examined. RESULTS: A total of 26,676 patients were included for analysis, of whom 162 patients (0.6%) had brain metastasis. Alveolar soft part sarcoma (6.3%), malignant hemangioendothelioma (3.1%) and malignant schwannoma (2.6%) showed higher incidence of brain metastasis. Deep-rooted tumor, trunk tumor, and histological high-grade tumor tended to show higher incidence of brain metastasis. CONCLUSION: Risk factors for brain metastasis were deep location, trunk development and histologically high-grade tumor, or specific histological subtypes.
• Ischemic Colitis Caused by Bowel Preparation for Colonoscopy.

  Takuji Kawamura, Naokuni Sakiyama, Kiyohito Tanaka, Isao Yokota, Koji Uno, Kenjiro Yasuda

  Gastroenterology research 14 5 296 - 303 2021年10月 

  Background: Ischemic colitis is an adverse event which may occur during bowel preparation for colonoscopy. This study aims to clarify both the incidence and the risk factors of this complication. Methods: This was a single-center, retrospective, observational study. All outpatients who were prescribed standardized preparation drugs for colonoscopy at the Kyoto Second Red Cross Hospital between November 2011 and March 2020 were included in the study. A split bowel preparation was carried out as follows; magnesium citrate with or without sodium picosulfate hydrate was/were used as a preparation drug on the day before the colonoscopy, and polyethylene glycol electrolyte solution or sodium phosphate was used on the morning of the endoscopic procedure. Patients were extracted from the electronic medical records and matched with the endoscopy database by examination date and hospital identification number. Following the endoscopic findings, both the incidence and risk factors for ischemic colitis arising after bowel preparation were examined. Results: Among the 14,924 patients analyzed, ischemic colitis was observed in 14 patients (0.09%). Multivariate analysis revealed that old age (≥ 75 years old) and strong preparation (magnesium citrate with sodium picosulfate and polyethylene glycol electrolyte solution) for constipated patients were independent risk factors for ischemic colitis (odds ratio: 3.64 (95% confidence interval (CI): 1.36 - 9.77) and 4.27 (95% CI: 1.45 - 12.53), respectively). Conclusions: The age 75 years and above and strong preparation for patients with constipation were independent risk factors for ischemic colitis prior to colonoscopy. Careful attention should be paid to bowel preparation before colonoscopy for patients aged ≥ 75 years and for those with constipation.
• Comparison of myopia progression between children wearing three types of orthokeratology lenses and children wearing single-vision spectacles.

  Yo Nakamura, Osamu Hieda, Isao Yokota, Satoshi Teramukai, Chie Sotozono, Shigeru Kinoshita

  Japanese journal of ophthalmology 65 5 632 - 643 2021年09月 

  PURPOSE: To evaluate factors related to myopia progression in children wearing either orthokeratology (OK) lenses or single-vision spectacles (SVS) for 2 years. STUDY DESIGN: Pooled-analysis retrospective intervention study. METHODS: This study involved 105 school-aged children wearing SVS who participated in the multi-center Myovision Study and 89 school-aged children wearing one of 3 OK lens types [Menicon Z Night (M, n = 27), αORTHO®-K (A, n = 32), and Emerald™ (E, n = 30)]. In the OK-lens patients, last examination was performed at ≥ 3-weeks post lens-wear discontinuation. Of the subjects, 102 SVS-Group and 79 OK-Group (M: n = 24, A: n = 28, and E: n = 27) children completed all examinations. A relationship between refractive error (RE) change and 7 factors (correction methods, baseline age, baseline RE, baseline axial length, gender, right or left eye, and follow-up period) was derived by multiple regression modeling. Via those same methods, we investigated the relationship between RE change and 7 factors including 3 OK-lens corrections. RESULTS: Related influence factors were correction method (0.85 D myopia reduction in the OK Group, P < 0.001), baseline age (0.16 D myopia reduction in older-age patients, P < 0.001), and baseline RE (0.12 D myopia reduction per 1 D myopia, P = 0.01). No relationship was found between RE change and OK-lens type. No serious adverse events occurred. CONCLUSION: Regardless of OK lens design, myopia progression in school-aged children was suppressed. The effect was examined not only via axial-length elongation but also RE change, and the myopia control effect by OK lenses was found to be 0.85 D over the 2-year period.
• Performance of Qualitative and Quantitative Antigen Tests for SARS-CoV-2 Using Saliva.

  Isao Yokota, Takayo Sakurazawa, Junichi Sugita, Sumio Iwasaki, Keiko Yasuda, Naoki Yamashita, Shinichi Fujisawa, Mutsumi Nishida, Satoshi Konno, Takanori Teshima

  Infectious disease reports 13 3 742 - 747 2021年08月24日 

  The rapid detection of SARS-CoV-2 is critical for the prevention of disease outbreaks. Antigen tests such as immunochromatographic assay (ICA) and chemiluminescent enzyme immunoassay (CLEIA) can yield results more quickly than PCR. We evaluated the performance of ICA and CLEIA using 34 frozen PCR-positive (17 saliva samples and 17 nasopharyngeal swabs [NPS]) and 309 PCR-negative samples. ICA detected SARS-CoV-2 in only 14 (41%) samples, with positivity rates of 24% in saliva and 59% in NPS. Notably, ICA detected SARS-CoV-2 in 5 of 6 samples collected within 4 days after symptom onset. CLEIA detected SARS-CoV-2 in 31 (91%) samples, with a positivity of 82% in saliva and 100% in NPS. These results suggest that the use of ICA should be limited to an earlier time after symptom onset and CLEIA is more sensitive and can be used in situations where quick results are required.
• Parenchymal destruction in asthma: Fixed airflow obstruction and lung function trajectory.

  Kaoruko Shimizu, Naoya Tanabe, Akira Oguma, Hirokazu Kimura, Masaru Suzuki, Isao Yokota, Hironi Makita, Susumu Sato, Toyohiro Hirai, Masaharu Nishimura, Satoshi Konno

  The Journal of allergy and clinical immunology 149 3 934 - 942 2021年08月24日 

  BACKGROUND: Fixed airflow obstruction (FAO) in asthma, particularly in nonsmokers, is generally believed to be caused by airway remodeling. However, parenchymal destruction may also contribute to FAO and longitudinal decline in forced expiratory volume in 1 second (FEV1). OBJECTIVES: To evaluate parenchymal destruction, we used emphysema indices, exponent D, and low-attenuation area percentage (LAA%) on computed tomography (CT), and test whether the parenchymal destruction and airway disease are independently associated with FAO and FEV1 decline in both smoking and nonsmoking asthma. METHODS: Exponent D, LAA%, wall area percentage at segmental airways, and airway fractal dimension (AFD) in those with asthma were measured on inspiratory CT and compared to those in patients with chronic obstructive pulmonary disease (COPD). RESULTS: Exponent D was lower and LAA% was higher in COPD (n = 42) and asthma with FAO (n = 101) than in asthma without FAO (n = 88). The decreased exponent D and increased LAA% were associated with FAO regardless of smoking status or asthma severity. In multivariable analysis, decreased exponent D and increased LAA% were associated with an increased odds ratio of FAO and decreased FEV1, irrespective of wall area percentage and airway fractal dimension. Moreover, decreased exponent D affected the longitudinal decline in FEV1 in those with severe asthma, independent of smoking status. CONCLUSIONS: Patients with asthma with FAO showed parenchymal destruction regardless of smoking status and asthma severity. Parenchymal destruction was associated with an accelerated FEV1 decline, suggesting the involvements of both airway and parenchyma in the pathophysiology of a subgroup of asthma.
• A novel strategy for SARS-CoV-2 mass screening with quantitative antigen testing of saliva: a diagnostic accuracy study.

  Isao Yokota, Peter Y Shane, Kazufumi Okada, Yoko Unoki, Yichi Yang, Sumio Iwasaki, Shinichi Fujisawa, Mutsumi Nishida, Takanori Teshima

  The Lancet Microbe 2 8 e397-e404  2021年08月 [査読有り]
   

  Background: Quantitative RT-PCR (RT-qPCR) of nasopharyngeal swab (NPS) samples for SARS-CoV-2 detection requires medical personnel and is time consuming, and thus is poorly suited to mass screening. In June, 2020, a chemiluminescent enzyme immunoassay (CLEIA; Lumipulse G SARS-CoV-2 Ag kit, Fujirebio, Tokyo, Japan) was developed that can detect SARS-CoV-2 nucleoproteins in NPS or saliva samples within 35 min. In this study, we assessed the utility of CLEIA in mass SARS-CoV-2 screening. Methods: We did a diagnostic accuracy study to develop a mass-screening strategy for salivary detection of SARS-CoV-2 by CLEIA, enrolling hospitalised patients with clinically confirmed COVID-19, close contacts identified at community health centres, and asymptomatic international arrivals at two airports, all based in Japan. All test participants were enrolled consecutively. We assessed the diagnostic accuracy of CLEIA compared with RT-qPCR, estimated according to concordance (Kendall's coefficient of concordance, W), and sensitivity (probability of CLEIA positivity given RT-qPCR positivity) and specificity (probability of CLEIA negativity given RT-qPCR negativity) for different antigen concentration cutoffs (0·19 pg/mL, 0·67 pg/mL, and 4·00 pg/mL; with samples considered positive if the antigen concentration was equal to or more than the cutoff and negative if it was less than the cutoff). We also assessed a two-step testing strategy post hoc with CLEIA as an initial test, using separate antigen cutoff values for test negativity and positivity from the predefined cutoff values. The proportion of intermediate results requiring secondary RT-qPCR was then quantified assuming prevalence values of RT-qPCR positivity in the overall tested population of 10%, 30%, and 50%. Findings: Self-collected saliva was obtained from 2056 participants between June 12 and Aug 6, 2020. Results of CLEIA and RT-qPCR were concordant in 2020 (98·2%) samples (Kendall's W=0·99). Test sensitivity was 85·4% (76 of 89 positive samples; 90% credible interval [CrI] 78·0-90·3) at the cutoff of 0·19 pg/mL; 76·4% (68 of 89; 68·2-82·8) at the cutoff of 0·67 pg/mL; and 52·8% (47 of 89; 44·1-61·3) at the cutoff of 4·0 pg/mL. Test specificity was 91·3% (1796 of 1967 negative samples; 90% CrI 90·2-92·3) at the cutoff of 0·19 pg/mL, 99·2% (1952 of 1967; 98·8-99·5) at the cutoff of 0·67 pg/mL, and 100·0% (1967 of 1967; 99·8-100·0) at the cutoff of 4·00 pg/mL. Using a two-step testing strategy with a CLEIA negativity cutoff of 0·19 pg/mL (to maximise sensitivity) and a CLEIA positivity cutoff of 4·00 pg/mL (to maximise specificity), the proportions of indeterminate results (ie, samples requiring secondary RT-qPCR) would be approximately 11% assuming a prevalence of RT-qPCR positivity of 10%, 16% assuming a prevalence of RT-qPCR positivity of 30%, and 21% assuming a prevalence of RT-qPCR positivity of 50%. Interpretation: CLEIA testing of self-collected saliva is simple and provides results quickly, and is thus suitable for mass testing. To improve accuracy, we propose a two-step screening strategy with an initial CLEIA test followed by confirmatory RT-qPCR for intermediate concentrations, varying positive and negative thresholds depending on local prevalence. Implementation of this strategy has expedited sample processing at Japanese airports since July, 2020, and might apply to other large-scale mass screening initiatives. Funding: Ministry of Health, Labour and Welfare, Japan.
• Mass screening of asymptomatic persons for SARS-CoV-2 using saliva.

  Isao Yokota, Peter Y Shane, Kazufumi Okada, Yoko Unoki, Yichi Yang, Tasuku Inao, Kentaro Sakamaki, Sumio Iwasaki, Kasumi Hayasaka, Junichi Sugita, Mutsumi Nishida, Shinichi Fujisawa, Takanori Teshima

  Clinical infectious diseases 73 3 e559 - e565 2021年08月 [査読有り][通常論文]
   

  BACKGROUND: COVID-19 has rapidly evolved to become a global pandemic due largely to the transmission of its causative virus through asymptomatic carriers. Detection of SARS-CoV-2 in asymptomatic people is an urgent priority for the prevention and containment of disease outbreaks in communities. However, few data are available in asymptomatic persons regarding the accuracy of PCR testing. Additionally, although self-collected saliva has significant logistical advantages in mass screening, its utility as an alternative specimen in asymptomatic persons is yet to be determined. METHODS: We conducted a mass-screening study to compare the utility of nucleic acid amplification, such as reverse transcriptase polymerase chain reaction (RT-PCR) testing, using nasopharyngeal swabs (NPS) and saliva samples from each individual in two cohorts of asymptomatic persons: the contact tracing cohort and the airport quarantine cohort. RESULTS: In this mass-screening study including 1,924 individuals, the sensitivity of nucleic acid amplification testing with nasopharyngeal and saliva specimens were 86% (90%CI:77-93%) and 92% (90%CI:83-97%), respectively, with specificities greater than 99.9%. The true concordance probability between the nasopharyngeal and saliva tests was estimated at 0.998 (90%CI:0.996-0.999) on the estimated airport prevalence at 0.3%. In positive individuals, viral load was highly correlated between NPS and saliva. CONCLUSION: Both nasopharyngeal and saliva specimens had high sensitivity and specificity. Self-collected saliva is a valuable specimen to detect SARS-CoV-2 in mass screening of asymptomatic persons.
• Evaluation of sensory loss obtained by modified-thoracoabdominal nerves block through perichondrial approach in patients undergoing gynecological laparoscopic surgery: a prospective observational study.

  Katsuhiro Aikawa, Isao Yokota, Yosuke Maeda, Yuji Morimoto

  Regional anesthesia and pain medicine 47 2 134 - 135 2021年07月20日
• Validation of dose distribution for liver tumors treated with real-time-image gated spot-scanning proton therapy by log data based dose reconstruction.

  Takahiro Yamada, Seishin Takao, Hidenori Koyano, Hideaki Nihongi, Yusuke Fujii, Shusuke Hirayama, Naoki Miyamoto, Taeko Matsuura, Kikuo Umegaki, Norio Katoh, Isao Yokota, Hiroki Shirato, Shinichi Shimizu

  Journal of radiation research 62 4 626 - 633 2021年07月10日 

  In spot scanning proton therapy (SSPT), the spot position relative to the target may fluctuate through tumor motion even when gating the radiation by utilizing a fiducial marker. We have established a procedure that evaluates the delivered dose distribution by utilizing log data on tumor motion and spot information. The purpose of this study is to show the reliability of the dose distributions for liver tumors treated with real-time-image gated SSPT (RGPT). In the evaluation procedure, the delivered spot information and the marker position are synchronized on the basis of log data on the timing of the spot irradiation and fluoroscopic X-ray irradiation. Then a treatment planning system reconstructs the delivered dose distribution. Dose distributions accumulated for all fractions were reconstructed for eight liver cases. The log data were acquired in all 168 fractions for all eight cases. The evaluation was performed for the values of maximum dose, minimum dose, D99, and D5-D95 for the clinical target volumes (CTVs) and mean liver dose (MLD) scaled by the prescribed dose. These dosimetric parameters were statistically compared between the planned dose distribution and the reconstructed dose distribution. The mean difference of the maximum dose was 1.3% (95% confidence interval [CI]: 0.6%-2.1%). Regarding the minimum dose, the mean difference was 0.1% (95% CI: -0.5%-0.7%). The mean differences of D99, D5-D95 and MLD were below 1%. The reliability of dose distributions for liver tumors treated with RGPT-SSPT was shown by the evaluation of the accumulated dose distributions.
• Refined ultrasonographic criteria for sinusoidal obstruction syndrome after hematopoietic stem cell transplantation.

  Mutsumi Nishida, Junichi Sugita, Shuichiro Takahashi, Takahito Iwai, Megumi Sato, Yusuke Kudo, Satomi Omotehara, Tatsunori Horie, Ryosuke Sakano, Hitoshi Shibuya, Isao Yokota, Akihiro Iguchi, Takanori Teshima

  International journal of hematology 114 1 94 - 101 2021年07月 

  Hepatic sinusoidal obstruction syndrome (SOS)/veno-occlusive disease is a life-threatening complication after hematopoietic stem cell transplantation (HSCT). We previously reported the efficacy of the Hokkaido Ultrasonography (US)-based scoring system (HokUS-10) for US findings. To establish easier-to-use criteria, we retrospectively evaluated US findings from 441 patients, including 30 patients with SOS using the HokUS-10 scoring system. Using logistic regression analysis, we established the novel diagnostic criteria HokUS-6. In the presence of ascites, US diagnosis was made in the presence of two of the following 6 parameters: moderate amount of ascites, the appearance of a paraumbilical vein blood flow signal, gallbladder wall thickening, portal vein dilatation, portal vein velocity decrease, and hepatic artery resistive index increase. The AUC, sensitivity, and specificity of HokUS-6 were 0.974 (95% confidence interval 0.962-0.990), 95.2%, and 96.9%, respectively. The scores were significantly higher in patients with severe SOS than in those with non-severe SOS (p = 0.013). Furthermore, the scores before HSCT were significantly higher in patients who developed SOS than in controls (p = 0.001). The HokUS-6 is an easy and useful way to diagnose and identify the risk of SOS.
• Randomized Controlled Trial of Simple Salt Reduction Instructions by Physician for Patients with Type 2 Diabetes Consuming Excessive Salt.

  Chikako Oyabu, Emi Ushigome, Yuriko Ono, Ayaka Kobayashi, Yoshitaka Hashimoto, Ryosuke Sakai, Hiroya Iwase, Hiroshi Okada, Isao Yokota, Toru Tanaka, Michiaki Fukui

  International journal of environmental research and public health 18 13 2021年06月28日 

  Objectives: We verified the clinical usefulness of an approach method in which a physician gives simple salt reduction instructions during outpatient visits to patients with type 2 diabetes. Methods: This study was an open-blind, randomized controlled trial. Subjects were outpatients with type 2 diabetes whose estimated salt intake using spot morning urine sample exceeded the target of salt intake. The control group (CG) was notified only of the current salt intake, whereas the intervention group (IG) was given the brief salt reduction instruction by a physician in addition to the information regarding their current salt intake. Results: The change in estimated salt intake was -0.6 g (from 10.1 to 9.5 g, p = 0.029) in the CG after 8 weeks, and -0.9 g (from 10.1 to 9.2 g, p = 0.001) in the IG, although there were no significant differences between them (p = 0.47). After 24 weeks, both groups no longer differed significantly from the baseline. In addition, multivariate linear regression analyses indicated that high salt intake and low estimated glomerular filtration rate at baseline were significantly associated with salt reduction after 8 weeks. Conclusions: Salt-reducing effects were observed after 8 weeks in both the IG and CG, but no significant difference was observed. Moreover, patients with high salt intake and renal disfunction may be more effective in accepting salt reduction instructions. Making patients aware of the importance of salt reduction through a physician is effective for continuous salt reduction, and it is important to continue regular and repetitive guidance.
• Logistic advantage of two-step screening strategy for SARS-CoV-2 at airport quarantine.

  Isao Yokota, Peter Y Shane, Takanori Teshima

  Travel medicine and infectious disease 43 102127 - 102127 2021年06月23日 [査読有り]
   

  BACKGROUND: Airport quarantine is required to reduce the risk of entry of travelers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is challenging for both high accuracy and rapid turn-around time to coexist in testing; polymerase chain reaction (PCR) is time-consuming with high accuracy, while antigen testing is rapid with less accuracy. However, there are few data on the concordance between PCR and antigen testing. METHODS: Arrivals at three international airports in Japan between July 29 and September 30, 2020 were tested for SARS-CoV-2 using self-collected saliva by a screening strategy with initial chemiluminescent enzyme immunoassay (CLEIA) followed by confirmatory nucleic acid amplification tests (NAAT) only for intermediate range antigen concentrations. RESULTS: Among the 95,457 persons entering Japan during the period, 88,924 (93.2%) were tested by CLEIA, and 0.29% (254/88,924) were found to be SARS-CoV-2 antigen positive (≥4.0 pg/mL). NAAT was required for confirmatory testing in 0.58% (513/88,924) with intermediate antigen concentrations (0.67-4.0 pg/mL) whereby the virus was detected in 6.6% (34/513). This two-step strategy reduced the utilization of NAAT to one out of every 173 test subjects. The estimated performance of this strategy did not show significant increase in false negatives as compared to performing NAAT in all subjects. CONCLUSIONS: Point of care testing by quantitative CLEIA using self-collected saliva is less labor-intensive and yields results rapidly, thus suitable as an initial screening test. Reserving NAAT for CLEIA indeterminate cases may prevent compromising accuracy while significantly improving the logistics of administering mass-screening at large venues.
• Combined assessment of pulmonary arterial enlargement and coronary calcification predicts the prognosis of patients with chronic obstructive pulmonary disease.

  Nozomu Takei, Masaru Suzuki, Naoya Tanabe, Akira Oguma, Kaoruko Shimizu, Hirokazu Kimura, Hironi Makita, Susumu Sato, Toyohiro Hirai, Isao Yokota, Satoshi Konno, Masaharu Nishimura

  Respiratory medicine 185 106520 - 106520 2021年06月23日 

  INTRODUCTION: In chronic obstructive pulmonary disease (COPD), chest computed tomography (CT) provides clinically important cardiovascular findings, which include diameter of pulmonary artery (PA), its ratio to the diameter of the aorta (PA:A ratio), and coronary artery calcium score (CACS). The clinical importance of these cardiovascular findings has not been fully assessed in Japan, where cardiovascular morbidity and/or mortality is reported to be much less compared with Western counterparts. METHODS: PA diameter and PA:A ratio were measured in 172 and 130 patients with COPD who enrolled in the Hokkaido COPD cohort study and the Kyoto University cohort, respectively. CACS was measured in 131 and 128 patients in each cohort. RESULTS: While the highest quartile group in PA diameter was associated with higher all-cause mortality compared to the lowest quartile group in both cohorts, individual assessments of PA:A ratio and CACS were not associated with the long-term clinical outcomes. When PA diameter and CACS were combined, patients with PA enlargement (diameter >29.5 mm) and/or coronary calcification (score >440.8) were associated with higher all-cause mortality in both cohorts. CONCLUSION: Combined assessment of PA enlargement and CACS was associated with poor prognosis, which provides a clinical advantage in management of patients with COPD even in geographical regions with lower risk of cardiovascular diseases.
• Effect of High Tibial Osteotomy on the Distribution of Subchondral Bone Density Across the Proximal Tibial Articular Surface of the Knee With Medial Compartment Osteoarthritis.

  Koji Iwasaki, Eiji Kondo, Shinji Matsubara, Masatake Matsuoka, Kaori Endo, Isao Yokota, Tomohiro Onodera, Norimasa Iwasaki

  The American journal of sports medicine 49 6 1561 - 1569 2021年05月 

  BACKGROUND: The effect of high tibial osteotomy (HTO) on the stress distribution across the knee joint is not completely understood. Subchondral bone density is considered to reflect the pattern of stress distribution across a joint surface. PURPOSE: To assess the distribution of subchondral bone density across the proximal tibia in nonarthritic knees and in the knees of patients with osteoarthritis (OA) before and after HTO. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: We retrospectively collected radiological and computed tomography data from 16 patients without OA (control group) and 17 patients with OA. Data from the OA group were collected before and 1.5 years after HTO. Subchondral bone density of the proximal tibia was assessed with computed tomography-osteoabsorptiometry. The locations and percentages represented by high-density areas (HDAs) on the articular surface were quantitatively analyzed. RESULTS: The ratio of the HDA of the medial compartment to the total HDA (medial ratio) was significantly higher in the preoperative OA group (mean, 80.1%) than in the control group (61.3%) (P < .001). After HTO, the medial ratio decreased significantly to 75.1% (P = .035 in comparison with preoperative values) and was significantly correlated with the hip-knee-ankle angle in both groups: control (r = -0.551; P = .033) and OA (r = -0.528; P = .043). The change in medial ratio after HTO was significantly correlated with the change in hip-knee-ankle angle (r = 0.587; P = .035). In the medial compartment, the HDA in the most lateral region of 4 subregions increased after HTO, but that in 3 medial subregions decreased. CONCLUSION: In this exploratory study, HTO shifted the HDA of the medial compartment of the proximal tibial articular surface toward the lateral compartment. In contrast, the HDA of the most lateral region of the medial compartment increased after HTO. This change in subchondral bone density may result from the change in stress distribution.
• Impact of Isolated High Home Systolic Blood Pressure and Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus: A 5-Year Prospective Cohort Study.

  Nobuko Kitagawa, Noriyuki Kitagawa, Emi Ushigome, Hidetaka Ushigome, Isao Yokota, Naoko Nakanishi, Masahide Hamaguchi, Mai Asano, Masahiro Yamazaki, Michiaki Fukui

  Journal of clinical medicine 10 9 2021年04月29日 

  BACKGROUND: A previous 2-year cohort study has shown that isolated high home systolic blood pressure (IH-HSBP) may increase the risk of diabetic nephropathy, using normal HBP as a reference. However, this association has not been previously assessed in the medium to long term. METHODS: This prospective 5-year cohort study of 424 patients, with normal or mildly increased albuminuria, investigated the effect of IH-HSBP on the risk of diabetic nephropathy in patients with type 2 diabetes mellitus. Diabetic nephropathy was defined as an advancement from normal or mildly increased albuminuira to moderate or severely increased albuminuria. RESULTS: Among 424 patients, 75 developed diabetic nephropathy during the study period. The adjusted odds ratio for developing diabetic nephropathy given IH-HSBP was 2.39 (95% confidence interval, 1.15-4.96, p = 0.02). The odds ratio for developing nephropathy in patients with IH-HSBP younger than 65 years was higher than that in patients with IH-HSBP older than 65 years. CONCLUSION: IH-HSBP was associated with an increased risk of diabetic nephropathy among type 2 diabetes mellitus patients with normal or mildly increased albuminuria in the medium to long term. The results support and strengthen previous reports. These findings suggest that IH-HSBP might be a useful marker in disease prognostication.
• The effect of rituximab on the quality of life of children with refractory nephrotic syndrome.

  Toshiyuki Takahashi, Takayuki Okamoto, Isao Yokota, Yasuyuki Sato, Asako Hayashi, Yasuhiro Ueda, Hayato Aoyagi, Michihiko Ueno, Norio Kobayashi, Kimiaki Uetake, Masanori Nakanishi, Tadashi Ariga

  Pediatrics international : official journal of the Japan Pediatric Society 2021年04月07日 

  BACKGROUND: Rituximab (RTX) is an effective treatment to maintaining remission in patients with nephrotic syndrome (NS), but there are few reports on the effect of RTX treatment on quality of life (QOL). The purpose of this study was to examine the effect of a periodically repeated RTX treatment from the perspective of QOL. METHODS: We systematically assessed the QOL of pediatric patients with refractory NS and parents' perceptions of their child's QOL through a two-year RTX treatment protocol. Pediatric patients from Hokkaido University Hospital with refractory NS who met our specific criteria were enrolled between January 2015 and December 2015. RTX infusion was performed 4 times at 6-month intervals, followed by mizoribine administration with early discontinuation of calcineurin inhibitors. QOL scores were measured by PedsQL at each RTX administration and evaluated 2 years later. RESULTS: Twenty-two patients were analyzed. Both the patient's QOL and their parents' perceptions of their QOL improved over our 2-year treatment protocol. Nevertheless, the parents' scores were lower than the patients' scores on all scales, with slower improvement. CONCLUSIONS: Our treatment protocol showed a significant improvement of QOL in patients with refractory NS. Although the risk of the RTX treatment should be considered, the treatment is useful for patients with refractory NS.
• Analysis of acute-phase toxicities of intensity-modulated proton therapy using a model-based approach in pharyngeal cancer patients.

  Koichi Yasuda, Hideki Minatogawa, Yasuhiro Dekura, Seishin Takao, Masaya Tamura, Nayuta Tsushima, Takayoshi Suzuki, Satoshi Kano, Takatsugu Mizumachi, Takashi Mori, Kentaro Nishioka, Motoyasu Shido, Norio Katoh, Hiroshi Taguchi, Noriyuki Fujima, Rikiya Onimaru, Isao Yokota, Keiji Kobashi, Shinichi Shimizu, Akihiro Homma, Hiroki Shirato, Hidefumi Aoyama

  Journal of radiation research 62 2 329 - 337 2021年03月10日 

  Pharyngeal cancer patients treated with intensity-modulated proton therapy (IMPT) using a model-based approach were retrospectively reviewed, and acute toxicities were analyzed. From June 2016 to March 2019, 15 pharyngeal (7 naso-, 5 oro- and 3 hypo-pharyngeal) cancer patients received IMPT with robust optimization. Simulation plans for IMPT and intensity-modulated X-ray therapy (IMXT) were generated before treatment. We also reviewed 127 pharyngeal cancer patients with IMXT in the same treatment period. In the simulation planning comparison, all of the normal-tissue complication probability values for dysphagia, dysgeusia, tube-feeding dependence and xerostomia were lower for IMPT than for IMXT in the 15 patients. After completing IMPT, 13 patients completed the evaluation, and 12 of these patients had a complete response. The proportions of patients who experienced grade 2 or worse acute toxicities in the IMPT and IMXT cohorts were 21.4 and 56.5% for dysphagia (P < 0.05), 46.7 and 76.3% for dysgeusia (P < 0.05), 73.3 and 62.8% for xerostomia (P = 0.43), 73.3 and 90.6% for mucositis (P = 0.08) and 66.7 and 76.4% for dermatitis (P = 0.42), respectively. Multivariate analysis revealed that IMPT was independently associated with a lower rate of grade 2 or worse dysphagia and dysgeusia. After propensity score matching, 12 pairs of IMPT and IMXT patients were selected. Dysphagia was also statistically lower in IMPT than in IMXT (P < 0.05). IMPT using a model-based approach may have clinical benefits for acute dysphagia.
• Impact of Inadequate Calorie Intake on Mortality and Hospitalization in Stable Patients with Chronic Heart Failure.

  Yoshikuni Obata, Naoya Kakutani, Shintaro Kinugawa, Arata Fukushima, Takashi Yokota, Shingo Takada, Taisuke Ono, Takeshi Sota, Yoshiharu Kinugasa, Masashige Takahashi, Hisashi Matsuo, Ryuichi Matsukawa, Ichiro Yoshida, Isao Yokota, Kazuhiro Yamamoto, Miyuki Tsuchihashi-Makaya

  Nutrients 13 3 2021年03月08日 

  Malnutrition is highly prevalent in patients with heart failure (HF), but the precise impact of dietary energy deficiency on HF patients' clinical outcomes is not known. We investigated the associations between inadequate calorie intake and adverse clinical events in 145 stable outpatients with chronic HF who had a history of hospitalization due to worsening HF. To assess the patients' dietary pattern, we used a brief self-administered diet-history questionnaire (BDHQ). Inadequate calorie intake was defined as <60% of the estimated energy requirement. In the total chronic HF cohort, the median calorie intake was 1628 kcal/day. Forty-four patients (30%) were identified as having an inadequate calorie intake. A Kaplan-Meier analysis revealed that the patients with inadequate calorie intake had significantly worse clinical outcomes including all-cause death and HF-related hospitalization during the 1-year follow-up period versus those with adequate calorie intake (20% vs. 5%, p < 0.01). A multivariate logistic regression analysis showed that inadequate calorie intake was an independent predictor of adverse clinical events after adjustment for various factors that may influence patients' calorie intake. Among patients with chronic HF, inadequate calorie intake was associated with an increased risk of all-cause mortality and rehospitalization due to worsening HF. However, our results are preliminary and larger studies with direct measurements of dietary calorie intake and total energy expenditure are needed to clarify the intrinsic nature of this relationship.
• Predictive power of home blood pressure measurement for cardiovascular outcomes in patients with type 2 diabetes: KAMOGAWA-HBP study.

  Emi Ushigome, Nobuko Kitagawa, Noriyuki Kitagawa, Toru Tanaka, Goji Hasegawa, Masayoshi Ohnishi, Sei Tsunoda, Hidetaka Ushigome, Isao Yokota, Naoto Nakamura, Mai Asano, Masahide Hamaguchi, Masahiro Yamazaki, Michiaki Fukui

  Hypertension research : official journal of the Japanese Society of Hypertension 44 3 348 - 354 2021年03月 

  Our previous study showed that the morning systolic blood pressure target should be <120 mmHg to prevent the onset or progression of diabetic nephropathy in patients with type 2 diabetes. In this study, we examined the prognostic values of home and clinical blood pressure for first cardiovascular events in the same cohort. Morning and evening home blood pressure measurements were obtained in triplicate for 14 consecutive days from the beginning of the study in a retrospective cohort of 1081 type 2 diabetes patients (44.5% women; median age 66.0 years) with no history of macrovascular complications. The first major cardiovascular event was the primary endpoint; the risk was examined by the Cox proportional hazards model. After a mean follow-up of 6.63 years, first-time cardiovascular events occurred in 119 patients (incidence, 16.6/1000 patient-years). Baseline morning systolic blood pressure (hazard ratio: 1.14, 95% CI 1.01-1.28) significantly predicted cardiovascular events, whereas clinical blood pressure did not. The adjusted hazard ratio (95% CI) for the incidence of cardiovascular events in patients with morning systolic blood pressure ≥135 mmHg tended to be higher than that in those with morning systolic blood pressure <125 mmHg [1.67 (0.94-2.97)]. Elevated home blood pressure measurement is a predictor of future cardiovascular events in type 2 diabetes patients and may be superior to clinical blood pressure measurement in this regard.
• Equivalent SARS-CoV-2 viral loads by PCR between nasopharyngeal swab and saliva in symptomatic patients.

  Isao Yokota, Takeshi Hattori, Peter Y Shane, Satoshi Konno, Atsushi Nagasaka, Kimihiro Takeyabu, Shinichi Fujisawa, Mutsumi Nishida, Takanori Teshima

  Scientific reports 11 1 4500 - 4500 2021年02月24日 [査読有り][通常論文]
   

  Emerging evidences have shown the utility of saliva for the detection of SARS-CoV-2 by PCR as alternative to nasopharyngeal swab (NPS). However, conflicting results have been reported regarding viral loads between NPS and saliva. We conducted a study to compare the viral loads between NPS and saliva in 42 COVID-19 patients. Viral loads were estimated by the cycle threshold (Ct) values. SARS-CoV-2 was detected in 34 (81%) using NPS with median Ct value of 27.4, and 38 (90%) using saliva with median Ct value of 28.9 (P = 0.79). Kendall's W was 0.82, showing a high degree of agreement, indicating equivalent viral loads in NPS and saliva. After symptom onset, the Ct values of both NPS and saliva continued to increase over time, with no substantial difference. Self-collected saliva has a detection sensitivity comparable to that of NPS and is a useful diagnostic tool with mitigating uncomfortable process and the risk of aerosol transmission to healthcare workers.
• The Relationships of Cerebral and Somatic Oxygen Saturation with Physiological Parameters in Pediatric Cardiac Surgery with Cardiopulmonary Bypass: Analysis Using the Random-Effects Model.

  Masataka Yamamoto, Toshihiro Mori, Takayuki Toki, Yusuke Itosu, Yasunori Kubo, Isao Yokota, Yuji Morimoto

  Pediatric cardiology 42 2 370 - 378 2021年02月 

  Recently, tissue oxygenation in pediatric heart surgery is measured by using near-infrared spectroscopy. Monitoring of cerebral oxygen saturation (ScO2) is most common but that of somatic tissue oxygen saturation (SrO2) is also gradually becoming widespread. However, the value of their monitoring is not well established. One of the reasons for this may be that the physiological factors affecting ScO2 and SrO2 have not been sufficiently clarified. Accordingly, we prospectively observed the changes in ScO2 and SrO2 simultaneously throughout cardiac surgery with cardiopulmonary bypass (CPB) in children weighing under 10 kg and evaluated their relationships with physiological parameters by using the random-effects model. ScO2 and SrO2 were measured with an INVOS 5100C (Somanetics, Troy, MI, USA). The random-effects analysis was applied for ScO2 and SrO2, as dependent variables, and seven physiological parameters (mean blood pressure, central venous pressure, rectal temperature, SaO2, hematocrit PaCO2, and pH) were entered as independent covariates. The analysis was performed during the pre-CPB, CPB, and post-CPB periods. Next, the same analysis was performed by dividing the patients into univentricular and biventricular physiological types. Forty-one children were evaluated. Through the whole surgical period, ScO2 correlated strongly with mean blood pressure regardless of the physiological type. On the other hand, the contribution of mean blood pressure to SrO2 was weak and various other parameters were related to SrO2 changes. Thus, the physiological parameters affecting ScO2 and SrO2 were rather different. Accordingly, the significance of monitoring of cerebral and somatic tissue oxygen saturation in pediatric cardiac surgery should be further evaluated.
• SARS-CoV-2 detection by fluorescence loop-mediated isothermal amplification with and without RNA extraction.

  Keisuke Taki, Isao Yokota, Tatsuya Fukumoto, Sumio Iwasaki, Shinichi Fujisawa, Masayoshi Takahashi, Saeki Negishi, Kasumi Hayasaka, Kaori Sato, Satoshi Oguri, Mutsumi Nishida, Junichi Sugita, Satoshi Konno, Tomoya Saito, Takanori Teshima

  Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 2 410 - 412 2021年02月 

  Rapid and simple point-of-care detection of SARS-CoV-2 is an urgent need to prevent pandemic. Reverse transcription loop-mediated isothermal amplification (RT-LAMP) can detect SARS-CoV-2 more rapidly than RT-PCR. Saliva is non-invasive specimen suitable for mass-screening, but data comparing utility of nasopharyngeal swab (NPS) and saliva in RT-LAMP test are lacking and it remains unclear whether SARS-CoV-2 could be detected by direct processing of samples without the need for prior RNA extraction saliva. In this study, we compared utility of saliva and NPS samples for the detection of SARS-CoV-2 by a novel RT-fluorescence LAMP (RT-fLAMP). The sensitivity and specificity of the RT-fLAMP with RNA extraction were 97% and 100%, respectively, with equivalent utility of NPS and saliva. However, sensitivity was decreased to 71% and 47% in NPS and saliva samples without RNA extraction, respectively, suggesting that RNA extraction process may be critical for the virus detection by RT-fLAMP.
• High-Density Lipoprotein Cholesterol and Cardiovascular Events in Patients with Stable Coronary Artery Disease Treated with Statins: An Observation from the REAL-CAD Study.

  Kazunori Omote, Isao Yokota, Toshiyuki Nagai, Ichiro Sakuma, Yoshihisa Nakagawa, Kiwamu Kamiya, Hiroshi Iwata, Katsumi Miyauchi, Yukio Ozaki, Kiyoshi Hibi, Takafumi Hiro, Yoshihiro Fukumoto, Hiroyoshi Mori, Seiji Hokimoto, Yasuo Ohashi, Hiroshi Ohtsu, Hisao Ogawa, Hiroyuki Daida, Satoshi Iimuro, Hiroaki Shimokawa, Yasushi Saito, Takeshi Kimura, Masunori Matsuzaki, Ryozo Nagai, Toshihisa Anzai

  Journal of atherosclerosis and thrombosis 29 1 50 - 68 2021年01月09日 

  AIM: The association between high-density lipoprotein cholesterol (HDL-C) level after statin therapy and cardiovascular events in patients with stable coronary artery disease (CAD) remains unclear. Thus, in this study, we sought to determine how HDL-C level after statin therapy is associated with cardiovascular events in stable CAD patients. METHODS: From the REAL-CAD study which had shown the favorable prognostic effect of high-dose pitavastatin in stable CAD patients with low-density lipoprotein cholesterol (LDL-C) ＜120 mg/dL, 9,221 patients with HDL-C data at baseline and 6 months, no occurrence of primary outcome at 6 months, and reported non-adherence for pitavastatin, were examined. The primary outcome was a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal ischemic stroke, or unstable angina requiring emergent admission after 6 months of randomization. Absolute difference and ratio of HDL-C levels were defined as (those at 6 months-at baseline) and (absolute difference/baseline)×100, respectively. RESULTS: During a median follow-up period of 4.0 (IQR 3.2-4.7) years, the primary outcome occurred in 417 (4.5%) patients. The adjusted risk of all HDL-C-related variables (baseline value, 6-month value, absolute, and relative changes) for the primary outcome was not significant (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.91-1.08, HR 1.03, 95% CI 0.94-1.12, HR 1.05, 95% CI 0.98-1.12, and HR 1.08, 95% CI 0.94-1.24, respectively). Furthermore, adjusted HRs of all HDL-C-related variables remained non-significant for the primary outcome regardless of on-treatment LDL-C level at 6 months. CONCLUSIONS: After statin therapy with modestly controlled LDL-C, HDL-C level has little prognostic value in patients with stable CAD.
• Impact of Smoking History on Pulmonary Metastasis-free Survival in Patients With Soft-tissue Sarcoma.

  Masatake Matsuoka, Masanori Okamoto, Tamotsu Soma, Isao Yokota, Ryuta Arai, Tomohiro Onodera, Eiji Kondo, Norimasa Iwasaki, Hiroaki Hiraga

  Cancer diagnosis & prognosis 1 2 89 - 94 2021年 

  BACKGROUND/AIM: Although smoking history is predictive of poor pulmonary metastasis-free survival (PMFS) in patients with epithelial tumors, the impact of smoking history on PMFS in those with soft-tissue sarcoma (STS) is not known. PATIENTS AND METHODS: Patients undergoing treatment for STS at our institutes between 2008 and 2017 were enrolled. Patients were excluded if they had metastatic lesion, or had a histopathological classification demonstrating small round-cell sarcoma. The impact of smoking history on PMFS and overall survival was examined with multivariate analysis using a Cox proportional hazards model. RESULTS: A total of 250 patients were retrospectively reviewed. Patients with smoking history had worse PMFS on multivariate analysis (hazard ratio=2.00, 95% confidence interval=1.12-3.60). On the other hand, smoking history did not significantly affect overall survival (hazard ratio=1.26, 95% confidence interval=0.61-2.58). CONCLUSION: Patients with STS need to be followed-up by frequent clinical assessments if they have a smoking history.
• Are simple verbal instructions sufficient to ensure that bladder volume does not deteriorate prostate position reproducibility during spot scanning proton therapy?

  Kentaro Nishioka, Kento Gotoh, Takayuki Hashimoto, Takashige Abe, Takahiro Osawa, Ryuji Matsumoto, Isao Yokota, Norio Katoh, Rumiko Kinoshita, Koichi Yasuda, Toshiaki Yakabe, Takaaki Yoshimura, Seishin Takao, Nobuo Shinohara, Hidefumi Aoyama, Shinichi Shimizu, Hiroki Shirato

  BJR|Open 3 1 20210064 - 20210064 2021年01月 

  The purpose of this study is to investigate whether verbal instructions are sufficient for bladder volume (BV) control not to deteriorate prostate position reproducibility in image-guided spot scanning proton therapy (SSPT) for localized prostate cancer. A total of 268 treatment sessions in 12 consecutive prostate cancer patients who were treated with image-guided SSPT with fiducial markers were retrospectively analyzed. In addition to strict rectal volume control procedures, simple verbal instructions to void urine one hour before the treatment were used here. The BV was measured by a Bladder Scan just before the treatment, and the prostate motion was measured by intraprostatic fiducial markers and two sets of X-ray fluoroscopy images. The correlation between the BV change and prostate motion was assessed by linear mixed-effects models and systematic and random errors according to the reproducibility of the BV. The mean absolute BV change during treatment was from −98.7 to 86.3 ml (median 7.1 ml). The mean absolute prostate motion of the patients in the left-right direction was −1.46 to 1.85 mm; in the cranial-caudal direction it was −6.10 to 3.65 mm, and in the anteroposterior direction −1.90 to 5.23 mm. There was no significant relationship between the BV change and prostate motion during SSPT. The early and late genitourinary and gastrointestinal toxicity was minimal with a minimum follow up of 4.57 years. Simple verbal instructions about urination was suggested to be sufficient to control the BV not to impact on the prostate motion and clinical outcomes in image-guided SSPT. Careful attention to BV change is still needed when the seminal vesicle is to be treated. Our data demonstrated that there was no apparent relationship between BV changes and prostate position reproducibility and simple verbal instruction about urination could be sufficient for image-guided SSPT.
• Multi-state model for predicting ocular progression in acute Stevens-Johnson syndrome/toxic epidermal necrolysis.

  Fumie Kinoshita, Isao Yokota, Hiroki Mieno, Mayumi Ueta, John Bush, Shigeru Kinoshita, Hirohiko Sueki, Hideo Asada, Eishin Morita, Masanori Fukushima, Chie Sotozono, Satoshi Teramukai

  PloS one 16 12 e0260730  2021年 

  This study aimed to clarify the etiologic factors predicting acute ocular progression in SJS/TEN, and identify patients who require immediate and intensive ophthalmological treatment. We previously conducted two Japanese Surveys of SJS/TEN (i.e., cases arising between 2005-2007 and between 2008-2010), and obtained the medical records, including detailed dermatological and ophthalmological findings, of 230 patients. Acute ocular severity was evaluated as none, mild, severe, and very severe. A multi-state model assuming the Markov process based on the Cox proportional hazards model was used to elucidate the specific factors affecting the acute ocular progression. Our findings revealed that of the total 230 patients, 23 (24%) of 97 cases that were mild at initial presentation worsened to severe/very severe. Acute ocular progression developed within 3 weeks from disease onset. Exposure to nonsteroidal anti-inflammatory drugs (NSAIDs) and younger patient age were found to be statistically significant for the progression of ocular severity from mild to severe/very severe [hazard ratio (HR) 3.83; 95% confidence interval (CI) 1.48 to 9.91] and none to severe/very severe [HR 0.98; 95% CI 0.97 to 0.99], respectively. The acute ocular severity score at worst-condition was found to be significantly correlated with ocular sequelae. Thus, our detailed findings on acute ocular progression revealed that in 24% of SJS/TEN cases with ocular involvement, ocular severity progresses even after initiating intensive treatment, and that in younger-age patients with a history of exposure to NSAIDs, very strict attention must be given to their ophthalmological appearances.
• Potential benefits of adaptive intensity-modulated proton therapy in nasopharyngeal carcinomas.

  Hideki Minatogawa, Koichi Yasuda, Yasuhiro Dekura, Seishin Takao, Taeko Matsuura, Takaaki Yoshimura, Ryusuke Suzuki, Isao Yokota, Noriyuki Fujima, Rikiya Onimaru, Shinichi Shimizu, Hidefumi Aoyama, Hiroki Shirato

  Journal of applied clinical medical physics 22 1 174 - 183 2021年01月 

  PURPOSE: To investigate potential advantages of adaptive intensity-modulated proton beam therapy (A-IMPT) by comparing it to adaptive intensity-modulated X-ray therapy (A-IMXT) for nasopharyngeal carcinomas (NPC). METHODS: Ten patients with NPC treated with A-IMXT (step and shoot approach) and concomitant chemotherapy between 2014 and 2016 were selected. In the actual treatment, 46 Gy in 23 fractions (46Gy/23Fx.) was prescribed using the initial plan and 24Gy/12Fx was prescribed using an adapted plan thereafter. New treatment planning of A-IMPT was made for the same patients using equivalent dose fractionation schedule and dose constraints. The dose volume statistics based on deformable images and dose accumulation was used in the comparison of A-IMXT with A-IMPT. RESULTS: The means of the Dmean of the right parotid gland (P < 0.001), right TM joint (P < 0.001), left TM joint (P < 0.001), oral cavity (P < 0.001), supraglottic larynx (P = 0.001), glottic larynx (P < 0.001), , middle PCM (P = 0.0371), interior PCM (P < 0.001), cricopharyngeal muscle (P = 0.03643), and thyroid gland (P = 0.00216), in A-IMPT are lower than those of A-IMXT, with statistical significance. The means of, D0.03cc , and Dmean of each sub portion of auditory apparatus and D30% for Eustachian tube and D0.5cc for mastoid volume in A-IMPT are significantly lower than those of A-IMXT. The mean doses to the oral cavity, supraglottic larynx, and glottic larynx were all reduced by more than 20 Gy (RBE = 1.1). CONCLUSIONS: An adaptive approach is suggested to enhance the potential benefit of IMPT compared to IMXT to reduce adverse effects for patients with NPC.
• Reliability of an ultrasonographical scoring system for diagnosis of sinusoidal obstruction syndrome/veno-occlusive disease in patients with hematopoietic stem cell transplantation.

  Takahito Iwai, Mutsumi Nishida, Junichi Sugita, Yusuke Kudo, Rika Takasugi, Isao Yokota, Ryo Takagi, Hitoshi Shibuya, Shuichiro Takahashi, Takanori Teshima

  Journal of medical ultrasonics (2001) 48 1 45 - 52 2021年01月 

  PURPOSE: Sinusoidal obstruction syndrome (SOS)/hepatic veno-occlusive disease (VOD) is a fatal complication after hematopoietic stem cell transplantation. We previously reported the usefulness of an ultrasonographical (US) scoring system, the Hokkaido US-based scoring system consisting of ten parameters (HokUS-10): (1) hepatomegaly in the left lobe and (2) right lobe, (3) dilatation of the main portal vein (PV), (4) hepatofugal flow in the main PV, (5) decreased velocity of the PV, (6) dilatation of the para-umbilical vein (PUV), (7) appearance of blood flow signal in the PUV, (8) gallbladder (GB) wall thickening, (9) ascites, and (10) increased resistive index of the hepatic artery, for the diagnosis of SOS/VOD. However, the reliability of this system among operators remains elusive. Therefore, we prospectively evaluated the reliability of HokUS-10. METHODS: Twenty-four healthy volunteers and 40 patients with liver dysfunction were enrolled. Inter- and intra-operator reliabilities were analyzed using three sonographers. RESULTS: The median concordance rate of HokUS-10 among three sonographers and intra-operator in 24 volunteers was 92% (95% CI: 73-98%) and 98% (95% CI: 92-100%), respectively. In all 64 cases, in terms of the reliability between two sonographers for three representative US parameters (amount of ascites, GB wall thickening, and appearance of PUV blood flow signal), the median concordance rate was more than 98% (95% CI: 86-106%). CONCLUSION: The inter- and intra-reliabilities of HokUS-10 were excellent. Thus, US might be a reliable tool for SOS/VOD diagnosis.
• Second primary malignancy after rituximab-containing immunochemotherapy for diffuse large B cell lymphoma.

  Yoshiaki Chinen, Kazuna Tanba, Ryo Takagi, Hitoji Uchiyama, Nobuhiko Uoshima, Kazuho Shimura, Shin-Ichi Fuchida, Miki Kiyota, Mitsushige Nakao, Taku Tsukamoto, Yuji Shimura, Tsutomu Kobayashi, Shigeo Horiike, Katsuya Wada, Chihiro Shimazaki, Hiroto Kaneko, Yutaka Kobayashi, Masafumi Taniwaki, Isao Yokota, Junya Kuroda

  Leukemia & lymphoma 61 14 3378 - 3386 2020年12月 [査読有り][通常論文]
   

  Extended post-therapy long-term survival of patients with diffuse large B cell lymphoma (DLBCL) may also lead to an increase of late adverse events. We retrospectively investigated the frequency and clinical manifestation of second primary malignancy (SPM) after rituximab-containing immunochemotherapy in patients with DLBCL treated at seven institutes belonging to the Kyoto Clinical Hematology Study Group (KOTOSG) from the perspective of the existence of past or synchronous cancer history. In a median follow-up period of 899 days, 69 SPMs were observed in 58 of 809 patients. The most frequent SPM was gastric cancer, followed by lung cancer and colorectal cancer. The cumulative incidence of SPM increased steadily over time and was not significantly influenced by the presence or absence of past or synchronous cancer history. Our study suggests the need for careful attention to SPM in patients with DLBCL in daily practice.
• Reply to authors.

  Isao Yokota, Kentaro Sakamaki, Peter Y Shane, Takanori Teshima

  Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 73 11 e3986-e3987  2020年10月26日
• Significance of fecal hemoglobin concentration for predicting risk of colorectal cancer after colonoscopy.

  Takuji Kawamura, Takato Inoue, Ryo Shinomiya, Hiroaki Sakai, Kana Amamiya, Naokuni Sakiyama, Atsushi Shirakawa, Yusuke Okada, Kasumi Sanada, Kojiro Nakase, Koichiro Mandai, Azumi Suzuki, Mai Kamaguchi, Atsushi Morita, Kenichi Nishioji, Kiyohito Tanaka, Koji Uno, Isao Yokota, Masao Kobayashi, Kenjiro Yasuda

  JGH open : an open access journal of gastroenterology and hepatology 4 5 898 - 902 2020年10月 

  Background and Aim: As the significance of the quantitative fecal immunochemical test (FIT) in patients who previously underwent a colonoscopy is unknown, this study aimed at investigating the association between fecal hemoglobin concentration and the risk of colorectal cancer (CRC). Methods and Results: We retrospectively analyzed FIT-positive patients who underwent a colonoscopy through our opportunistic annual screening program from April 2010 to March 2017 at the Kyoto Second Red Cross Hospital. We stratified them into no colonoscopy and past colonoscopy (>5 years or ≤5 years) groups based on whether they had a history of undergoing a colonoscopy and analyzed the correlation between fecal hemoglobin concentration and advanced neoplasia or invasive cancer detection in each group. We analyzed 1248 patients with positive FIT results. There were 748 (59.9%), 198 (15.9%), and 302 (24.2%) patients in the no colonoscopy, past colonoscopy (>5 years), and past colonoscopy (≤5 years) groups, respectively. In the no colonoscopy group, the advanced neoplasia detection rate significantly increased with the fecal hemoglobin concentration (P < 0.001). However, no significant trend was observed in the past colonoscopy (both >5 years and ≤5 years) group (P = 0.982). No invasive cancer was detected in the past colonoscopy (≤5 years) group. Conclusion: The risk of CRC might be low even if fecal hemoglobin concentration was high, especially in those who underwent colonoscopy within 5 years.
• Immunological Gene Signature Associated With the Tumor Microenvironment of Pancreatic Cancer After Neoadjuvant Chemotherapy.

  Yuma Hane, Takahiro Tsuchikawa, Toru Nakamura, Kanako C Hatanaka, Tatsuro Saito, Kimitaka Tanaka, Yoshitsugu Nakanishi, Toshimichi Asano, Takehiro Noji, Keisuke Okamura, Toshiaki Shichinohe, Isao Yokota, Yutaka Hatanaka, Satoshi Hirano

  Pancreas 49 9 1240 - 1245 2020年10月 [査読有り][通常論文]
   

  OBJECTIVES: Neoadjuvant chemotherapy (NAC) has improved overall survival in patients with pancreatic ductal adenocarcinoma (PDAC), but its effects on immune gene signatures are unknown. Here, we examined the immune transcriptome after NAC for PDAC. METHODS: Resected tumor specimens were obtained from 140 patients with PDAC who received surgery first (n = 93) or NAC (n = 47). Six patients were randomly selected from each group, and RNA was extracted from tumor tissues. We compared 770 immune-related genes among the 2 groups using nCounterPanCancer Immune Profiling (NanoString Technologies, Seattle, Wash). Gene clusters were classified into 14 immune function groups based on gene ontology argolism by nSolver 4.0 software (NanoString Technologies), and corresponding immune cell function scores were compared. RESULTS: Eleven genes (LY86, SH2D1A, CD247, TIGIT, CR2, CD83, LAMP3, CXCR4, DUSP4, SELL, and IL2RA) were significantly downregulated in the NAC group. Gene expression analysis showed that the functions of regulatory T cells, B cells, and natural killer CD56 dim cells were significantly decreased in the NAC group. CONCLUSIONS: Neoadjuvant chemotherapy may suppress regulatory T cells and B-cell function in the PDAC microenvironment. The 11 identified genes could be useful for predicting the efficacy of NAC and could be therapeutic targets for PDAC.
• Type 2 diabetes is an independent predictor of lowered peak aerobic capacity in heart failure patients with non-reduced or reduced left ventricular ejection fraction.

  Takahiro Abe, Takashi Yokota, Arata Fukushima, Naoya Kakutani, Takashi Katayama, Ryosuke Shirakawa, Satoshi Maekawa, Hideo Nambu, Yoshikuni Obata, Katsuma Yamanashi, Ippei Nakano, Shingo Takada, Isao Yokota, Koichi Okita, Shintaro Kinugawa, Toshihisa Anzai

  Cardiovascular diabetology 19 1 142 - 142 2020年09月19日 [査読有り][通常論文]
   

  BACKGROUND: Although type 2 diabetes mellitus (T2DM) is one of the most frequent comorbidities in patients with chronic heart failure (CHF), the effects of T2DM on the exercise capacity of CHF patients are fully unknown. Here, we tested the hypothesis that the coexistence of T2DM lowers CHF patients' peak aerobic capacity. METHODS: We retrospectively analyzed the cases of 275 Japanese CHF patients with non-reduced ejection fraction (left ventricular ejection fraction [LVEF] ≥ 40%) or reduced EF (LVEF < 40%) who underwent cardiopulmonary exercise testing. We divided them into diabetic and nondiabetic groups in each CHF cohort. RESULTS: The mean peak oxygen uptake (VO2) value was 16.87 mL/kg/min in the non-reduced LVEF cohort and 15.52 mL/kg/min in the reduced LVEF cohort. The peak VO2 was lower in the diabetics versus the nondiabetics in the non-reduced LVEF cohort with the mean difference (95% confidence interval [95% CI]) of - 0.93 (- 1.82 to - 0.04) mL/kg/min and in the reduced LVEF cohort with the mean difference of - 1.05 (- 1.96 to - 0.15) mL/kg/min, after adjustment for age-squared, gender, anemia, renal function, LVEF, and log B-type natriuretic peptide (BNP). The adjusted VO2 at anaerobic threshold (AT), a submaximal aerobic capacity, was also decreased in the diabetic patients with both non-reduced and reduced LVEFs. Intriguingly, the diabetic patients had a lower adjusted peak O2 pulse than the nondiabetic patients in the reduced LVEF cohort, but not in the non-reduced LVEF cohort. A multivariate analysis showed that the presence of T2DM was an independent predictor of lowered peak VO2 in CHF patients with non-reduced LVEF and those with reduced LVEF. CONCLUSIONS: T2DM was associated with lowered peak VO2 in CHF patients with non-reduced or reduced LVEF. The presence of T2DM has a negative impact on CHF patients' exercise capacity, and the degree of impact is partly dependent on their LV systolic function.
• Therapeutic Angiogenesis Using Bone Marrow-Derived Mononuclear Cell Implantation for Patients With Critical Limb-Threatening Ischemia Caused by Thromboangiitis Obliterans - Study Protocol for a Multicenter Prospective Interventional Trial.

  Ayumu Fujioka, Kenji Yanishi, Keisuke Shoji, Yusuke Hori, Hirofumi Kawamata, Arito Yukawa, Isao Yokota, Satoshi Teramukai, Ayumu Yamada, Satoaki Matoba

  Circulation reports 2 10 630 - 634 2020年09月15日 

  Background: Patients with thromboangiitis obliterans (TAO) can develop critical limb-threatening ischemia (CLTI) and require limb amputation. Smoking cessation and exercise therapy are recommended as standard treatments, and revascularization by bypass surgery or endovascular therapy (EVT) is required for patients with CLTI. However, there are many cases in which revascularization is difficult because of vascular characteristics, and the patency rate after revascularization remains unsatisfactory. Therapeutic angiogenesis using bone marrow-derived mononuclear cell (BM-MNC) implantation is used clinically, with many trials demonstrating long-term efficacy and safety of the technique in patients with CLTI, especially that caused by TAO. To expand the use of BM-MNCs implantation in clinical practice, further evidence is required in patients with CLTI caused by TAO. Methods and Results: This trial is a multicenter, prospective, non-randomized interventional trial of an Advanced Medicine B treatment approach. We aim to enroll 25 patients aged 20-80 years with Fontaine classification Stage III or IV, who will undergo BM-MNC implantation. The primary endpoint is the improvement in skin perfusion pressure of the target limb 180 days after BM-MNC implantation, whereas secondary endpoints are improvements in rest pain or ulcer size. We will also investigate rates of major or minor amputation, survival, and adverse events during follow-up. Conclusions: BM-MNC implantation is expected to be an efficacious and feasible treatment for patients with CLTI caused by TAO.
• Correction to: Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07: a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG).

  Tomoro Hishiki, Kimikazu Matsumoto, Miki Ohira, Takehiko Kamijo, Hiroyuki Shichino, Tatsuo Kuroda, Akihiro Yoneda, Toshinori Soejima, Atsuko Nakazawa, Tetsuya Takimoto, Isao Yokota, Satoshi Teramukai, Hideto Takahashi, Takashi Fukushima, Takashi Kaneko, Junichi Hara, Michio Kaneko, Hitoshi Ikeda, Tatsuro Tajiri, Akira Nakagawara

  International journal of clinical oncology 25 9 1744 - 1745 2020年09月 [査読有り][通常論文]
   

  In the October 2018 issue of International Journal of Clinical Oncology.
• Factors related to memory absence and delusional memories in patients in intensive care units managed with light sedation.

  Ayako Noguchi, Koji Hosokawa, Fumimasa Amaya, Isao Yokota

  Intensive & critical care nursing 59 102830 - 102830 2020年08月 [査読有り][通常論文]
   

  OBJECTIVES: Currently, light sedation is typically given to patients in intensive care units and studies have not extensively examined the factors related to absences or abnormalities of their memories. We, therefore, analysed the factors related to the absence/abnormalities of patients' memories in intensive care units. RESEARCH METHODOLOGY: A secondary analysis of previously collected survey data examining patients' experiences in an intensive care unit was undertaken (n = 405; women = 38%; median age = 70 years). To observe absent or distorted memories, patients were interviewed after leaving the intensive care unit. We analysed key factors through content analysis of the interviews and field notes. SETTING: The intensive care unit of a university hospital. MAIN OUTCOME MEASURE: Patients' absent or distorted memories after leaving the intensive care unit. RESULTS: Half the patients reported an absence of memories. This was associated with old age and with longer duration of mechanical ventilation. Absent or fragmentary memories were not distressing. Fragmentary and fearful intensive care unit memories were associated with being older. Delusional memories, some of which reflected actual events, were present in 3% of patients. CONCLUSION: Absence of memories were not distressing, delusional memories occurred less and these memories could comprise of an event in ICU that is difficult for patients to understand.
• Effect of Lomerizine Hydrochloride on Preventing Strokes in Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.

  Akiko Watanabe-Hosomi, Ikuko Mizuta, Takashi Koizumi, Isao Yokota, Mao Mukai, Ai Hamano, Masaki Kondo, Akihiro Fujii, Masaru Matsui, Koushun Matsuo, Keita Ito, Satoshi Teramukai, Kei Yamada, Masanori Nakagawa, Toshiki Mizuno

  Clinical neuropharmacology 2020年07月10日 [査読有り][通常論文]
   

  BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an orphan disease clinically characterized by migraine, recurrent strokes, and dementia. Currently, there are no disease-modifying therapies, and it is difficult to prevent cerebral ischemic events in CADASIL patients by conventional antithrombotic medication. We hypothesized that an antimigraine agent, lomerizine hydrochloride, may prevent strokes in CADASIL patients, based on its effect on increasing cerebral blood flow. SUBJECTS AND METHODS: This was an open-labeled clinical trial in which 30 adult CADASIL patients received lomerizine at 10 mg/d. Numbers of symptomatic strokes during the 2 years after the start of lomerizine administration were compared with those in the 2 years before its initiation. The effect of lomerizine on preventing strokes was evaluated based on the incidence rate ratio (IR) calculated with the Mantel-Haenszel method. RESULTS: When including all 30 patients (analysis 1), the IR was less than 1 (0.46; 95% confidence interval [CI], 0.19-1.12) but did not reach significance. To evaluate the effect of lomerizine on secondary prevention, subgroups of 15 patients with stroke episodes occurring any time before lomerizine administration (analysis 2) and 10 patients with stroke episodes during the 2 years before lomerizine administration (analysis 3) were analyzed. The IR values were 0.33 (95% CI, 0.12-0.94) in analysis 2 and 0.17 (95% CI, 0.04-0.67) in analysis 3. CONCLUSIONS: Our results suggest the effect of lomerizine on preventing secondary stroke in CADASIL patients.
• A new risk stratification model for intravesical recurrence, disease progression, and cancer-specific death in patients with non-muscle invasive bladder cancer: the J-NICE risk tables.

  Makito Miyake, Hideyasu Matsuyama, Satoshi Teramukai, Fumie Kinoshita, Isao Yokota, Hiroaki Matsumoto, Keiji Shimada, Mitsuru Kinjyo, Tatsuro Shimokama, Koji Okumura, Masaya Yomenori, Hideki Enokida, Masayuki Nakagawa, Yasushi Nakai, Kiyohide Fujimoto

  International journal of clinical oncology 25 7 1364 - 1376 2020年07月 [査読有り][通常論文]
   

  BACKGROUND: The aim of this study is to establish new risk tables for the current clinical setting, enabling short- and long-term risk stratification for recurrence, progression, and cancer-specific death after transurethral resection in non-muscle invasive bladder cancer (NMIBC). Currently available risk tables lack input from the 2004 World Health Organization grading system and risk prediction for cancer-specific death. METHODS: This was a multi-institutional database study of 1490 patients diagnosed with NMIBC (the development cohort). A multivariate Fine and Gray subdistribution hazard model was used to assess the prognostic impact of various factors. Patients were classified into low-, intermediate-, and high-risk groups according to a sum of the weight of selected factors, and predicted cumulative rates were calculated. Internal validation was conducted using 200 bootstrap resamples to assess the optimism for the c-index and estimate a bias-corrected c-index. External validation of the developed risk table was performed on an independent dataset of 91 patients. RESULTS: The Japanese NIshinihon uro-onCology Extensive collaboration group (J-NICE) risk stratification table was derived from six, five, and two factors for recurrence, progression, and cancer-specific death, respectively. The internal validation bias-corrected c-index values were 0.619, 0.621, and 0.705, respectively. The application of the J-NICE table to an external dataset resulted in c-indices for recurrence, progression, and cancer-specific death of 0.527, 0.691, and 0.603, respectively. CONCLUSIONS: We propose a novel risk stratification model that predicts outcomes of treated NMIBC and may overcome the shortcomings of existing risk models. Further external validation is required to strengthen its clinical impact.
• Inclination of Blumensaat's line influences on the accuracy of the quadrant method in evaluation for anterior cruciate ligament reconstruction.

  Koji Iwasaki, Masayuki Inoue, Yasuhiko Kasahara, Koichiro Tsukuda, Harunori Kawahara, Isao Yokota, Eiji Kondo, Norimasa Iwasaki, Kazunori Yasuda

  Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 28 6 1885 - 1893 2020年06月 [査読有り][通常論文]
   

  PURPOSE: The quadrant method is used to evaluate the bone tunnel position with the grid based on the Blumensaat's line in anterior cruciate ligament (ACL) reconstruction. This study aimed to clarify the influence of variation in the Blumensaat's line on the accuracy of the quadrant method measurements. METHODS: A retrospective review of the radiological records of patients aged 18-30 years who underwent computed tomography (CT) scanning of the knee joint was conducted. The Blumensaat's line inclination angle (BIA), along with the most posterior point of the posterior condyle (point P) position using the quadrant method and morphology of the Blumensaat's line were measured on true lateral transparent three-dimensional CT images of the distal femoral condyle in 147 patients. Statistical analysis was conducted to determine associations among these measurements. RESULTS: BIA was 37.5° (standard deviation 4.2°; range 27°-48°). The point P position was significantly correlated with BIA in the high/low (R2 = 0.590, P < 0.0001) and deep/shallow (R2 = 0.461, P < 0.0001) directions. The morphology of the Blumensaat's line was straight in 35 knees (23.8%); whereas, the remaining 112 knees (76.2%) were not straight but had some hill on the Blumensaat's line. No significant difference among the morphological variation of the Blumensaat's line was observed in BIA and the point P position. CONCLUSION: There was a strong correlation between BIA and the point P measured using the quadrant method, suggesting the influence of the Blumensaat's line on the accuracy of the quadrant method measurements in ACL reconstruction. As for the clinical relevance, surgeons should be careful in application of the quadrant method for ACL reconstruction, because the variation of the Blumensaat's line inclination influences the accuracy of this method.
• Analysis of the optimal psoas muscle mass index cut-off values, as measured by computed tomography, for the diagnosis of loss of skeletal muscle mass in Japanese people.

  Masatsugu Ohara, Goki Suda, Megumi Kimura, Osamu Maehara, Tomoe Shimazaki, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Tomoe Kobayashi, Minoru Uebayashi, Ryo Takagi, Isao Yokota, Tsuyoshi Shimamura, Naoya Sakamoto

  Hepatology research : the official journal of the Japan Society of Hepatology 50 6 715 - 725 2020年06月 [査読有り][通常論文]
   

  This study aimed to determine the optimal psoas muscle mass index (PMI) cut-off values for diagnosis of skeletal muscle mass loss. METHODS: We evaluated PMI in two groups of normal controls: a medical check-up group and a liver donation candidate group. We analyzed two novel PMI cut-off values, one based on the mean - two standard deviations (2SD) and one based on the lower 5%. Skeletal muscle mass index (SMI) evaluations using computed tomography (sliceOmatic; TomoVision) and bioelectrical impedance analysis and PMI evaluation were undertaken simultaneously. We analyzed the correlation between our PMI cut-off values and the Japan Society of Hepatology-defined SMI cut-off values. The prevalence of skeletal muscle mass loss in patients with liver disease was assessed using the novel PMI cut-off values. RESULTS: In 504 normal controls aged ≤50 years, the PMI cut-off values based on mean -2SD and the lower 5% were set at 3.30 cm2 /m2 for men and 1.69 cm2 /m2 for women and 3.74 cm2 /m2 for men and 2.29 cm2 /m2 for women, respectively. The PMI cut-off values based on the lower 5% alone showed that skeletal muscle mass loss increased with age. Furthermore, they correlated well with Japan Society of Hepatology-defined SMI (sliceOmatic) cut-off values and showed a significantly higher prevalence of skeletal muscle mass loss in patients with liver cirrhosis than those without liver cirrhosis. CONCLUSIONS: We propose the following PMI cut-off values: 3.74 cm2 /m2 for male individuals and 2.29 cm2 /m2 for female individuals. These cut-off values can facilitate accurate diagnosis and management of sarcopenia in patients with chronic liver disease.
• Long-term Progression of Ocular Surface Disease in Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

  Yamato Yoshikawa, Mayumi Ueta, Hideki Fukuoka, Tsutomu Inatomi, Isao Yokota, Satoshi Teramukai, Norihiko Yokoi, Shigeru Kinoshita, Kensuke Tajiri, Tsunehiko Ikeda, Chie Sotozono

  Cornea 39 6 745 - 753 2020年06月 [査読有り][通常論文]
   

  PURPOSE: To investigate the details of the long-term progression of ocular surface cicatrization in eyes with ocular sequelae caused by Stevens-Johnson syndrome (SJS)/toxic epidermal necrosis (TEN). METHODS: In 105 eyes of 66 patients with SJS/TEN, the severity of ocular sequelae was retrospectively evaluated using an ocular surface grading score (OSGS) at 2 time points separated by a greater than 5-year interval. The OSGS included 7 ocular surface components (conjunctivalization, neovascularization, opacification, keratinization, symblepharon, and upper/lower conjunctival-sac shortening) evaluated into grades 0 to 3 (maximum total OSGS: 21), with the worsening of each component and total OSGS evaluated at the greater than 5-year interval. Moreover, we evaluated whether upper-tarsus and lid-margin scarring are factors that affect ocular surface cicatrization progression. RESULTS: In 35 (33.3%) of 105 eyes, the total OSGS worsened during the follow-up period. Partial conjunctivalization (score 1-2) progressed more frequently to total conjunctivalization (score 3) than to no conjunctivalization (score 0) (OR [95% CI]; 5.6 [1.6-20.3]). Partial keratinization (score 1-2) also had a high risk of progression into total keratinization (41.0 [6.3-266.5]). In all cases, keratinization progressed only in the eyes with total conjunctivalization (conjunctivalization score 3). Severity of upper-tarsus scarring or lid-margin scarring affected the worsening of the total OSGS. CONCLUSIONS: In 66 patients with chronic-phase SJS/TEN, ocular surface cicatrization progressed in 33.3% of the 105 eyes during the long-term follow-up period of over 5 years. More than 50% of the partial conjunctivalization eyes progressed toward total conjunctivalization. The partial keratinization eyes had a high possibility of progressing to total keratinization; that is, the so-called "end-stage" status.
• Development of a multiplex RT-PCR assay and statistical evaluation of its use in forensic identification of vaginal fluid.

  Tomoko Akutsu, Isao Yokota, Ken Watanabe, Koichi Sakurada

  Legal medicine (Tokyo, Japan) 45 101715 - 101715 2020年05月08日 [査読有り][通常論文]
   

  The identification of vaginal fluid from casework samples of sexual assaults provides important probative evidence of vaginal intercourse. The aim of this study was to establish a more specific procedure for identifying vaginal fluids for forensic purposes. Vaginal fluid marker candidates have been evaluated quantitatively and five of these markers (ESR1, SERPINB13, KLK13, CYP2B7P1, MUC4) have been amplified simultaneously by a multiplex reverse transcription-polymerase chain reaction (RT-PCR) procedure. Each amplicon has been separated and quantified automatically using chip electrophoresis. Subsequently, in the present study, detectability and cross-reactivity of the developed multiplex procedure were assessed in detail using various forensically relevant body fluids. Then, a cutoff value for the positive detection of vaginal fluids was set for each marker by Youden index. The ability of the multiplex RT-PCR assay to distinguish between vaginal and other body fluids was evaluated statistically using a likelihood ratio (LR) that was estimated using a Bayesian estimation approach to consider the infrequency of detection. A high LR was obtained when all five markers showed positive results (LR = 4.33 × 109; 95% credible interval, 3.95 × 107 -2.87 × 1012). The developed procedure was validated using vaginal fluid samples under various conditions. High LRs were found for aged vaginal fluid stains, although each amplicon peak was low. It was also able to identify vaginal stains mixed with other body fluids. In conclusion, the multiplex RT-PCR-based procedure followed by the statistical evaluation using LR could be a powerful tool for the objective identification of vaginal fluids.
• Predictive value of serum amyloid a levels for requirement of concomitant methotrexate in tocilizumab initiation: A post hoc analysis of the SURPRISE study.

  Masaru Kato, Yuko Kaneko, Yoshiya Tanaka, Masayuki Inoo, Hitomi Kobayashi-Haraoka, Koichi Amano, Masayuki Miyata, Yohko Murakawa, Hidekata Yasuoka, Shintaro Hirata, Hayato Nagasawa, Eiichi Tanaka, Nobuyuki Miyasaka, Hisashi Yamanaka, Kazuhiko Yamamoto, Isao Yokota, Tatsuya Atsumi, Tsutomu Takeuchi

  Modern rheumatology 30 3 442 - 449 2020年05月 [査読有り][通常論文]
   

  Objectives: To identify predictive factors for remission by tocilizumab monotherapy in rheumatoid arthritis (RA) patients.Methods: This is a post hoc analysis of the SURPRISE study, a 2-year randomized, controlled study comparing the efficacy of tocilizumab with (ADD-ON) and without methotrexate (SWITCH). The primary endpoint was DAS28-ESR remission (<2.6) at week 24. The change in modified total Sharp score from baseline to week 52 (ΔmTSS/year) was also assessed as an endpoint. The effect of clinical parameters at baseline on remission was estimated by logistic regression analysis.Results: In SWITCH (n = 96), CRP, SAA, RF, and DAS28 at baseline showed predictive value for DAS28 remission in unadjusted analysis. Adjusted analysis confirmed SAA and DAS28 as predictive factors, with SAA having the highest value (ROC-AUC = 0.731). Furthermore, structural remission (ΔmTSS/year ≤ 0.5) rate was significantly higher in patients with SAA of < 50.0 μg/mL than other patients. In contrast, in ADD-ON (n = 98), only DAS28 showed predictive value for DAS28 remission. In patients with SAA < 50.0 μg/mL, both DAS28 remission and structural remission rate were comparable between SWITCH and ADD-ON.Conclusion: RA patients with low SAA levels at baseline may benefit similarly from tocilizumab with and without methotrexate.Trial registration number: NCT01120366.
• Association between preexisting lung involvements and the risk of diffuse alveolar hemorrhage in patients with microscopic polyangiitis: A multi-center retrospective cohort study.

  Takashi Kida, Tadashi Tanaka, Isao Yokota, Keiichi Tamagaki, Tomoya Sagawa, Masatoshi Kadoya, Takahiro Yamada, Kazuki Fujioka, Makoto Wada, Masataka Kohno, Noriya Hiraoka, Atsushi Omoto, Wataru Fukuda, Yutaka Kawahito

  Modern rheumatology 30 2 338 - 344 2020年03月 [査読有り][通常論文]
   

  Objectives: To identify the factors associated with the risk of diffuse alveolar hemorrhage (DAH) in patients with microscopic polyangiitis (MPA), focusing on other preexisting lung involvements such as interstitial lung disease (ILD) and airway disease.Methods: In this retrospective cohort study, we analyzed consecutive patients with myeloperoxidase-antineutrophil cytoplasmic antibody-positive MPA who had undergone chest computed tomography (CT) before starting treatment between 2006 and 2016. Patients who already had DAH at initial CT imaging were excluded. CT images were evaluated for the presence of ILD and airway disease. The association between preexisting lung involvements and the development of DAH was assessed using logistic regression models adjusted for various clinical characteristics.Results: We identified 113 patients (median age 72 years; median follow-up duration 39 months), and 27 (24%) of them developed DAH during the follow-up. Airway disease was identified in 41 (36%) patients and was independently associated with the development of DAH (adjusted odds ratio 6.86, 95% confidence interval 1.85-25.4). However, ILD identified in 45 (40%) patients was not associated with DAH.Conclusion: Our findings suggest that DAH in MPA occurs frequently in patients with airway disease. Attention to preexisting airway disease may help predict the development of DAH.
• A Bayesian basket trial design that borrows information across strata based on the similarity between the posterior distributions of the response probability.

  Kei Fujikawa, Satoshi Teramukai, Isao Yokota, Takashi Daimon

  Biometrical journal. Biometrische Zeitschrift 62 2 330 - 338 2020年03月 [査読有り][通常論文]
   

  Basket trials simultaneously evaluate the effect of one or more drugs on a defined biomarker, genetic alteration, or molecular target in a variety of disease subtypes, often called strata. A conventional approach for analyzing such trials is an independent analysis of each of the strata. This analysis is inefficient as it lacks the power to detect the effect of drugs in each stratum. To address these issues, various designs for basket trials have been proposed, centering on designs using Bayesian hierarchical models. In this article, we propose a novel Bayesian basket trial design that incorporates predictive sample size determination, early termination for inefficacy and efficacy, and the borrowing of information across strata. The borrowing of information is based on the similarity between the posterior distributions of the response probability. In general, Bayesian hierarchical models have many distributional assumptions along with multiple parameters. By contrast, our method has prior distributions for response probability and two parameters for similarity of distributions. The proposed design is easier to implement and less computationally demanding than other Bayesian basket designs. Through a simulation with various scenarios, our proposed design is compared with other designs including one that does not borrow information and one that uses a Bayesian hierarchical model.
• Calcineurin inhibitors for adult-onset Still's disease: a multicentre retrospective cohort study.

  Hiroyuki Nakamura, Yuichiro Fujieda, Masato Tarumi, Hirohiko Kitakawa, Ryo Hisada, Ikuma Nakagawa, Atsushi Noguchi, Takashi Kurita, Hiroshi Kataoka, Hideki Kasahara, Yoshiharu Amasaki, Isao Yokota, Tatsuya Atsumi

  Clinical and experimental rheumatology 2020年02月19日 [査読有り][通常論文]
   

  OBJECTIVES: To clarify the efficacy and safety of calcineurin inhibitors (CNI) for treating adult-onset Still's disease (AOSD). METHODS: This multicentre historical cohort study enrolled the consecutive patients with AOSD according to Yamaguchi classification criteria. The endpoints were set as the time from the initiation of treatment to events, the persistency rate of CNI and safety. Based on the recurrent event data analysis, these endpoints were evaluated for each event. We divided the events into two groups according to the treatment that included CNI or conventional therapy without CNI. RESULTS: One hundred seventy-eight patients with 247 events were analysed. CNI were predominantly used in 72 events with a recurrent history, typical skin rash, high ferritin levels, and/or severe complications such as macrophage activation syndrome, disseminated intravascular coagulation, serositis, meningitis. CNI led to a significantly longer event-free survival (hazard ratio: 0.57, 95% confidential interval: 0.32-0.99) after adjustment of concomitant medications. Subgroup analysis showed that CNI were effective for AOSD patients with high ALT level (hazard ratio: 0.11, 95% confidential interval: 0.02-0.59) and severe complications (hazard ratio: 0.11, 95% confidential interval: 0.01-0.94). The persistency rate of CNI was 71% at 5th year. Adverse events occurred more frequently in the CNI group (18% versus 8%, p=0.02); however, CNI did not involve in increased risk of adverse events, including nephrotoxicity, after adjustment (p=0.23). CONCLUSIONS: Our retrospective analysis suggested that CNI could be an effective and safe option for treating AOSD.
• Comparison of the efficacy of cryotherapy and compression therapy for preventing nanoparticle albumin-bound paclitaxel-induced peripheral neuropathy: A prospective self-controlled trial.

  Yuko Kanbayashi, Koichi Sakaguchi, Takeshi Ishikawa, Yoshimi Ouchi, Katsuhiko Nakatsukasa, Yusuke Tabuchi, Fuminao Kanehisa, Minako Hiramatsu, Ryo Takagi, Isao Yokota, Norito Katoh, Tetsuya Taguchi

  Breast (Edinburgh, Scotland) 49 219 - 224 2020年02月 [査読有り][通常論文]
   

  BACKGROUND: Recently, the efficacy of cryotherapy and compression therapy to prevent taxane-induced peripheral neuropathy has been reported. We prospectively compared the efficacy of cryotherapy using a frozen glove (FG) and compression therapy using a surgical glove (SG) to prevent nanoparticle albumin-bound paclitaxel (nab-PTX)-induced peripheral neuropathy. PATIENTS AND METHODS: Breast cancer patients who received 260 mg/m2 of nab-PTX were eligible to participate in this trial. Patients wore a FG on one hand (60 min) without changing and two SGs of the same size (i.e., one size smaller than the size that best fit their hand) on the other hand (90 min) during chemotherapy. Peripheral neuropathy was evaluated at each treatment cycle using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, the Patient Neurotoxicity Questionnaire (PNQ), and the Functional Assessment of Cancer Therapy-Taxane subscale. Temperatures at each fingertip in both groups were measured thermographically. RESULTS: Between August 2017 and March 2019, 43 patients were enrolled and 38 were evaluated. No cases showed discordance of peripheral neuropathy between each gloved group in cases of CTCAE ≥ grade 2. In cases of PNQ ≥ grade D, using the Nam equivalence test, the upper test (P = 0.0329) and lower test (P = 0.0052) both showed negative results in comparisons between each gloved group. Fingertip temperature was significantly lower in the FG group than in the SG group after treatment (P < 0.0001). CONCLUSIONS: It seems to be no difference in incidence of nab-PTX-induced peripheral neuropathy using either cryotherapy or compression therapy.
• Seasonal variation in home blood pressure and its relationship with room temperature in patients with type 2 diabetes

  Ushigome, E., Kitagawa, N., Kitae, A., Kimura, T., Iwai, K., Oyabu, C., Ushigome, H., Yokota, I., Hamaguchi, M., Asano, M., Yamazaki, M., Fukui, M.

  Diabetes and Vascular Disease Research 17 1 1479164119883986  2020年 [査読有り][通常論文]
  
• A Novel Strategy for SARS-CoV-2 Mass-Screening Using Quantitative Antigen Testing of Saliva

  Isao Yokota, Peter Y. Shane, Kazufumi Okada, Yokota Unoki, Yichi Yang, Sumio Iwasaki, Shinichi Fujisawa, Mutsumi Nishida, Takanori Teshima

  SSRN Electronic Journal 2020年 [査読有り]
  
• Effect of Lomerizine Hydrochloride on Preventing Strokes in Patients With Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy.

  Akiko Watanabe-Hosomi, Ikuko Mizuta, Takashi Koizumi, Isao Yokota, Mao Mukai, Ai Hamano, Masaki Kondo, Akihiro Fujii, Masaru Matsui, Koushun Matsuo, Keita Ito, Satoshi Teramukai, Kei Yamada, Masanori Nakagawa, Toshiki Mizuno

  Clinical neuropharmacology 43 5 146 - 150 2020年 

  BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an orphan disease clinically characterized by migraine, recurrent strokes, and dementia. Currently, there are no disease-modifying therapies, and it is difficult to prevent cerebral ischemic events in CADASIL patients by conventional antithrombotic medication. We hypothesized that an antimigraine agent, lomerizine hydrochloride, may prevent strokes in CADASIL patients, based on its effect on increasing cerebral blood flow. SUBJECTS AND METHODS: This was an open-labeled clinical trial in which 30 adult CADASIL patients received lomerizine at 10 mg/d. Numbers of symptomatic strokes during the 2 years after the start of lomerizine administration were compared with those in the 2 years before its initiation. The effect of lomerizine on preventing strokes was evaluated based on the incidence rate ratio (IR) calculated with the Mantel-Haenszel method. RESULTS: When including all 30 patients (analysis 1), the IR was less than 1 (0.46; 95% confidence interval [CI], 0.19-1.12) but did not reach significance. To evaluate the effect of lomerizine on secondary prevention, subgroups of 15 patients with stroke episodes occurring any time before lomerizine administration (analysis 2) and 10 patients with stroke episodes during the 2 years before lomerizine administration (analysis 3) were analyzed. The IR values were 0.33 (95% CI, 0.12-0.94) in analysis 2 and 0.17 (95% CI, 0.04-0.67) in analysis 3. CONCLUSIONS: Our results suggest the effect of lomerizine on preventing secondary stroke in CADASIL patients.
• Validation of the Developed Eating Activities Questionnaire in Working People with Disabilities: A Cross-Sectional Study

  Tashiro Yuto, Aoyama Tomoki, Nishida Yuichi, Yamaoka Ayaka, Suzuki Yusuke, Horii Takayoshi, Arai Hiroaki, Yamaguchi Yutaka, Wada Naoya, Yokota Isao

  Asian Journal of Occupational Therapy 16 1 87 - 93 社団法人 日本作業療法士協会 2020年 

  Objectives: There are only a few functional evaluations that non-medical personnel can perform and interpret without guidance. Here, we have created a questionnaire that focused on eating activities, which can be used to evaluate motor function easily because most people could relate to eating activities. This study aimed to verify the reliability and validity of the developed questionnaire by comparing it with clinical evaluations for upper extremity function.

  Methods: This was a cross-sectional study. Patients who have cerebrovascular disease history with disabilities in the upper limb were included in the study. The questionnaire on eating activities was answered by the patients themselves. Upper extremity function was evaluated with the Fugl-Meyer Assessment (FMA). Work efficiency was evaluated with the General Aptitude Test Battery. Reliability of the questionnaire was assessed by test-retest reliability. Validity was evaluated using a correlation analysis.

  Results: The study included 16 participants. The results indicated that all items had sufficient reliability. The correlation between the questionnaire score of the hand and the FMA score of the wrist, hand, and arm was statistically significant.

  Conclusions: The developed questionnaire was reliable and significantly related to clinical evaluation of upper extremity functions. This questionnaire is of great value to patients with stroke to understand their functions.

• Usefulness of Exercise for Home Blood Pressure Control in People with Diabetes: A Study Protocol for a Crossover Randomized Controlled Trial.

  Keiko Iwai, Emi Ushigome, Isao Yokota, Saori Majima, Naoko Nakanishi, Yoshitaka Hashimoto, Hiroshi Okada, Takafumi Senmaru, Masahide Hamaguchi, Mai Asano, Masahiro Yamazaki, Michiaki Fukui

  Diabetes, metabolic syndrome and obesity : targets and therapy 13 4747 - 4753 2020年 

  Background: The coexistence of hypertension and diabetes mellitus significantly increases the risk of macrovascular complications in patients with diabetes. Home blood pressure is important because it is more strongly associated with target organ damage and total mortality than clinic blood pressure measurements. Regular moderate aerobic exercise has antihypertensive effects. This study aims to examine the effect of aerobic exercise therapy on blood pressure at home in patients with diabetes. Patients and Methods: In this crossover randomized controlled trial, 110 patients with type 2 diabetes will be randomly assigned to two groups: an exercise preceding group and an exercise lagging group. During the exercise period, patients will be instructed to walk either 30 minutes twice each day or 60 minutes once each day for at least 3 days per week. During the non-exercise period, patients will be permitted to perform physical activity associated with activities of daily life. Patients will be followed up for 56 days. The primary outcome will be the mean nocturnal blood pressure from day 24 to 28 during the exercise period compared to that during the non-exercise period. The secondary outcome will include variation in nocturnal blood pressure, mean blood pressure values and variation of morning and evening blood pressure from day 24 to 28 in the exercise period compared to the non-exercise period, body weight, body mass index and bioelectrical impedance analysis. Biochemical tests such as hemoglobin A1c level, blood glucose level, serum lipid profile, renal function, uric acid levels and liver function tests will also be measured. Discussion: This randomized controlled trial will provide critical information regarding the effectiveness of moderate exercise on nocturnal blood pressure reduction. If successful, the results of this randomized controlled trial may increase exercise motivation in people with diabetes and may lead to improvement or prevention of target organ damage and overall mortality. Trial Registration: Trial registration: University Hospital Medical Information Network, UMIN 000035973. Protocol version number: R000040969. Registration date: February 22, 2019. Recruitment began: June 19, 2019. The date of completion of recruitment: July 3, 2020. URL: http://www.umin.ac.jp.
• Correction: Association of fatty pancreas with pancreatic endocrine and exocrine function.

  Hayato Miyake, Junichi Sakagami, Hiroaki Yasuda, Yoshio Sogame, Ryusuke Kato, Kanetoshi Suwa, Katsuyuki Dainaka, Tomoki Takata, Isao Yokota, Yoshito Itoh

  PloS one 15 7 e0236915  2020年 [査読有り][通常論文]
   

  [This corrects the article DOI: 10.1371/journal.pone.0209448.].
• Five-year follow-up outcomes after Descemet's stripping automated endothelial keratoplasty: a retrospective study.

  Koichi Wakimasu, Koji Kitazawa, Kanae Kayukawa, Isao Yokota, Tsutomu Inatomi, Osamu Hieda, Chie Sotozono, Shigeru Kinoshita

  BMJ open ophthalmology 5 1 e000354  2020年 [査読有り][通常論文]
   

  Objective: To assess graft survival and endothelial cell density (ECD) over a 5-year follow-up period after Descemet's stripping automated endothelial keratoplasty (DSAEK). Methods and analysis: This retrospective study involved 130 eyes of 130 consecutive patients with Fuchs endothelial corneal dystrophy (FECD), non-FECD bullous keratopathy (BK) (non-FECD) or BK post-trabeculectomy or tube-shunt surgery (glaucoma with bleb) who underwent DSAEK between August 2007 and January 2012 and were followed for more than 5 years postoperatively. Patients with previous keratoplasty, graft suture failure, primary graft failure, postoperative endophthalmitis and ocular infection were excluded. Graft survival and ECD was then examined in all patients who underwent DSAEK and completed the postoperative follow-up period. The association between clinical factors and 5-year graft survival after DSAEK was analysed with multivariate logistic regression analysis. Results: The overall graft survival rate at 5 years postoperatively was 85%, yet significantly poorer in the glaucoma with bleb eyes (47%) than in the FECD (100%) or non-FECD (90%) eyes (p<0.01, log-rank test). In the FECD, non-FECD and glaucoma with bleb eyes, the mean ECD at 5 years postoperatively was 1054 cells/mm2, 1137 cells/mm2 and 756 cells/mm2, respectively. Multivariate logistic regression analysis showed history of trabeculectomy or tube-shunt surgery and postoperative allograft rejection to be negative factors for graft survival at 5 years after DSAEK (OR 0.01, 95% CI 0.00 to 0.10 and OR 0.02, 95% CI 0.00 to 0.33, respectively). Conclusion: Our findings show that at 5 years postoperatively, the surgical outcome after DSAEK was poorer in eyes after trabeculectomy or tube-shunt surgery. Trial registration number: UMIN000024891.
• Indications for Cold Polypectomy Stratified by the Colorectal Polyp Size: A Systematic Review and Meta-Analysis.

  Takuji Kawamura, Yoji Takeuchi, Isao Yokota, Nobumasa Takagaki

  Journal of the anus, rectum and colon 4 2 67 - 78 2020年 [査読有り][通常論文]
   

  Objectives: Cold polypectomy (CP) is widely used because of its safety profile. This systematic review and meta-analysis aimed to clarify the indications for CP based on polyp size. Methods: We searched PubMed and the Cochrane Library for randomized controlled trials that compared cold snare polypectomy (CSP) and other procedures for polyps ≤10 mm. Large-scale prospective observational studies were also searched to assess delayed bleeding rates. The studies were integrated to assess the risk ratio for incomplete resection rates according to polyp size. The Cochrane risk of bias tool was used to evaluate the study bias. The certainty of cumulative evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. Results: We found 280 articles and reviewed their eligibility. We selected and extracted 12 randomized controlled trials and 3 prospective observational studies. The risk ratio of incomplete resection of polyps ≤10 mm using CSP compared with hot snare polypectomy (HSP) was 1.36 (95% confidence interval [CI], 0.92-2.01). The risk ratio for incomplete removal using CSP compared with cold forceps polypectomy (CFP) was 0.50 (95% CI, 0.31-0.82). For polyps ≤3 mm, the risk ratio of CSP compared with CFP was 1.40 (95% CI, 0.39-4.95). Certainty of cumulative evidence was considered low. No delayed bleeding after CP was reported after the treatment of 3446 polyps. Conclusions: CSP and HSP may result in the same complete resection rates for polyps ≤10 mm. For polyps ≤3 mm, CFP and CSP may have the same resection rates (PROSPERO registration number: CRD42019122132).
• Anterior and posterior ratio of corneal surface areas: A novel index for detecting early stage keratoconus.

  Motohiro Itoi, Koji Kitazawa, Isao Yokota, Koichi Wakimasu, Yuko Cho, Yo Nakamura, Osamu Hieda, Satoshi Teramukai, Shigeru Kinoshita, Chie Sotozono

  PloS one 15 4 e0231074  2020年 [査読有り][通常論文]
   

  PURPOSE: To evaluate the diagnostic ability of the ratio of anterior and posterior corneal surface areas (As/Ps) comparing with other keratoconus screening indices in distinguishing forme fruste keratoconus (FFKC) from normal eyes. METHODS: In this comparative study, 13 eyes of 13 patients with FFKC, 29 eyes of 29 patients with keratoconus (KC) and 88 eyes of 88 patients with normal subjects were involved. The As/Ps measured by the anterior segment optical coherence tomography (AS-OCT) and other indices measured by AS-OCT and rotating Scheimpflug-based corneal tomography were evaluated. The area under receiver-operating-characteristics (AU-ROC) was calculated to assess the diagnostic ability in discriminating FFKC from normal eyes. RESULTS: The As/Ps, the Belin/Ambrosio display enhanced ectasia total derivation value (BAD-D) and posterior and anterior elevation values showed the AU-ROC 0.9 or more in differentiating FFKC from normal eyes (0.980, 0.951, 0.924 and 0.903, respectively). The sensitivity and specificity were 0.92 and 0.96 for the As/Ps, 1.00 and 0.90 for BAD-D, 0.85 and 0.86 for posterior elevation value, and 0.85 and 0.96 for anterior elevation value, respectively. CONCLUSIONS: Among the several indices for keratoconus screening which we evaluated, the As/Ps obtained by AS-OCT had the large AU-ROC with high sensitivity and specificity in detecting FFKC, which was comparable with BAD-D obtained by rotating Scheimpflug-based corneal tomography. The As/Ps may provide information for improving the diagnostic accuracy of KC, even in the initial stage of the disease.
• Risk factors for cytomegalovirus disease with cytomegalovirus re-activation in patients with rheumatic disease.

  Shunya Kaneshita, Takashi Kida, Isao Yokota, Hidetake Nagahara, Takahiro Seno, Makoto Wada, Masataka Kohno, Yutaka Kawahito

  Modern rheumatology 30 1 109 - 115 2020年01月 [査読有り][通常論文]
   

  Objective: To assess risk factors for cytomegalovirus (CMV) disease with CMV re-activation in patients with rheumatic disease.Methods: The clinical data of consecutive patients with rheumatic disease who experienced CMV re-activation were examined. We evaluated the difference in various baseline factors at the first detection of CMV pp65 antigenemia on the development of CMV disease using logistic regression models. The changes of laboratory data in the 4 weeks before CMV re-activation were also assessed.Results: We identified 80 patients (median age [interquartile range] = 65.0 years [51.5-74.0]) with CMV re-activation. Oral candidiasis, serum albumin ≤30 g/L, and CMV pp65-positive cell count >5.6/105 polymorphonuclear leukocyte cells were found to be associated with CMV disease (odds ratio [OR] [95% CI] = 9.99 [2.02-49.50], 11.4 [1.94-67.40] and 6.80 [1.63-28.30], respectively). Moreover, decreases in serum albumin level and blood lymphocyte count in the 4 weeks before CMV re-activation also predicted CMV disease (OR [95% CI] = 2.02 [1.07-3.8] and 1.96 [1.09-3.54], respectively).Conclusion: In CMV re-activation patients with rheumatic disease, the presence of oral candidiasis, high CMV pp65 positive cell count, and hypoalbuminemia are possible risk factors for CMV disease.
• Evaluation of the efficacy of simplified nutritional instructions from physicians on dietary salt restriction for patients with type 2 diabetes mellitus consuming excessive salt: protocol for a randomized controlled trial.

  Emi Ushigome, Chikako Oyabu, Makoto Shiraishi, Nobuko Kitagawa, Aya Kitae, Keiko Iwai, Hidetaka Ushigome, Isao Yokota, Masahide Hamaguchi, Masahiro Yamazaki, Michiaki Fukui

  Trials 20 1 761 - 761 2019年12月23日 [査読有り][通常論文]
   

  BACKGROUND: Hypertension is present in more than 50% of patients with type 2 diabetes mellitus. Dietary salt restriction is recommended for the management of high blood pressure. Instructions on dietary salt restriction, provided by a dietitian, have been shown to help patients reduce their salt intake. However, appointments for the dietitians in hospitals are often already fully booked, making it difficult for patients to receive instructions on the same day as the outpatient clinic visit. AIM: The aim of this trial is to test a new intervention to assess whether guidance on dietary salt restriction provided by physicians during outpatient visits is effective in reducing salt intake in patients with type 2 diabetes mellitus who have an excessive salt intake. METHODS: In this unblinded randomized controlled trial (RCT), a total of 200 patients, male or female, aged between 20 and 90 years, who have type 2 diabetes mellitus and consume excessive salt will be randomly assigned to two groups: an intervention group and a control group. In addition to being given routine treatment, participants in the intervention group will be given individual guidance on restricting their dietary salt intake by a physician upon enrollment. The control group will only be given routine treatment. Participants will be followed up for 24 weeks. The primary outcome will be dietary salt intake, which will be assessed at baseline and at 8, 16, and 24 weeks. The secondary outcomes, including body weight, body mass index, hemoglobin A1c level, blood pressure, blood glucose level, serum lipid profile, and urinary albumin excretion level, will be assessed at baseline and at 8, 16, and 24 weeks. DISCUSSION: The results of this RCT have the potential to provide a simple and novel clinical approach to reduce salt intake among patients with type 2 diabetes, making regular visits to their physician, in outpatient facilities. This protocol will contribute to the literature because it describes a practical intervention that has not been tested previously, and it may serve as guidance to other researchers interested in testing similar interventions. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN), UMIN000028809. Registered retrospectively on 24 August 2017. http://www.umin.ac.jp.
• Prediction of delayed platelet engraftment after autologous stem cell transplantation for B-cell non-Hodgkin lymphoma.

  Junko Yamaguchi, Yoshiaki Chinen, Tomoko Takimoto-Shimomura, Hiroaki Nagata, Ayako Muramatsu, Kodai Kuriyama, Muneo Ohshiro, Yoshiko Hirakawa, Toshiki Iwai, Hitoji Uchiyama, Nobuhiko Uoshima, Hiroto Kaneko, Mitsushige Nakao, Taku Tsukamoto, Yuji Shimura, Tsutomu Kobayashi, Shigeo Horiike, Isao Yokota, Junya Kuroda

  Leukemia & lymphoma 60 14 3434 - 3441 2019年12月 [査読有り][通常論文]
   

  Delayed platelet engraftment (DPE) is occasionally observed despite prompt neutrophil engraftment after autologous peripheral blood stem cell transplantation (auto-PBSCT). To identify risk factors for DPE and to develop a simple and clinically applicable system for predicting the time required for platelet recovery, we conducted a multi-institutional retrospective study in 144 patients with B-cell non-Hodgkin lymphoma who underwent auto-PBSCT. In a median observation period of 930 days (range: 25-5272 days), 139 patients successfully achieved platelet engraftment (≥50.0 × 109/L). The median duration for platelet engraftment was 19 days, and 130 patients had platelet engraftment within 40 days after auto-PBSCT; however, the other 14 patients failed to achieve platelet engraftment within 60 days. These 14 patients with DPE required a significantly greater number of apheresis procedures and had a lower pre-apheresis absolute lymphocyte count (PA-ALC) compared to those without DPE. Importantly, multivariate analysis revealed that the number of transplanted CD34+ cells (≤2.0 × 106/kg), number of required apheresis procedures (≥3 days), and PA-ALC (≤1.0 × 109/L) were independently associated with a longer time for platelet engraftment after auto-PBSCT. By incorporating these three independent factors as variables, we generated a new scoring system for prediction of the time and probability for platelet engraftment after auto-PBSCT.
• Isolated high home systolic blood pressure in patients with type 2 diabetes is a prognostic factor for the development of diabetic nephropathy: KAMOGAWA-HBP study.

  Nobuko Kitagawa, Emi Ushigome, Toru Tanaka, Goji Hasegawa, Naoto Nakamura, Masayoshi Ohnishi, Sei Tsunoda, Hidetaka Ushigome, Isao Yokota, Noriyuki Kitagawa, Masahide Hamaguchi, Mai Asano, Masahiro Yamazaki, Michiaki Fukui

  Diabetes research and clinical practice 158 107920 - 107920 2019年12月 [査読有り][通常論文]
   

  BACKGROUND: Isolated high home systolic blood pressure (IH-HSBP) has been revealed to be correlated with cardiovascular disease and diabetic nephropathy, however, the prognostic significance of IH-HSBP with the development of diabetic nephropathy is unclear. METHODS: In this prospective 2-year cohort study of 477 patients with normoalbuminuria, we investigated the effect of IH-HSBP on the development of diabetic nephropathy defined by diabetic nephropathy advanced from normoalbuminuira to micro or macroalbuminuria. RESULTS: Among 477 patients, 67 patients showed the development of diabetic nephropathy. In the multivariate logistic regression analyses, IH-HSBP was prognostic factor for the development of nephropathy after adjusting for sex, age, duration of diabetes mellitus, body mass index, total cholesterol, hemoglobin A1c, creatinine, smoking habits and use of renin-angiotensin-aldosterone system inhibitors (odds ratio: 2.53, 95% confidence interval: 1.16-5.56, p = 0.020). CONCLUSION: IH-HSBP in patients with type 2 diabetes with normoalbuminuria was prognostic factor for the development of diabetic nephropathy. We should pay more attention to IH-HSBP to prevent the development of diabetic nephropathy.
• Association of trajectories of cognitive function with cause-specific mortality and medical and long-term care costs.

  Yu Taniguchi, Akihiko Kitamura, Tatsuro Ishizaki, Yoshinori Fujiwara, Tomohiro Shinozaki, Satoshi Seino, Seigo Mitsutake, Hiroyuki Suzuki, Yuri Yokoyama, Takumi Abe, Tomoko Ikeuchi, Isao Yokota, Yutaka Matsuyama, Shoji Shinkai

  Geriatrics & gerontology international 19 12 1236 - 1242 2019年12月 [査読有り][通常論文]
   

  AIM: Cognitive decline increases mortality risk through dementia-related pathways and might be associated with increased healthcare costs. Using up to 12 years of repeated measures data, we identified trajectories in cognitive function among community-dwelling older Japanese adults. We then examined whether these trajectories were associated with all-cause and cause-specific mortality, and differences in healthcare costs. METHODS: A total of 1736 adults aged ≥65 years who were free of disabling dementia completed annual assessments during 2002-2014. Cognitive function was assessed with the Mini-Mental State Examination. The average number of follow-up assessments was 3.9, and the total number of observations was 6824 during the follow-up period. RESULTS: We identified five trajectory patterns in cognitive function (high, second, third, fourth, and low) during the 12-year follow-up period. The low (2.0%) and fourth (2.2%) trajectory groups had higher hazard ratios for cardiovascular disease mortality, and hazard ratios for other cause mortality were significantly higher for the third (16.8%) and second (38.8%) trajectory groups than for the high trajectory group (40.3%). Until 5 years of follow up, participants in the two lower-trajectory groups had higher mean combined monthly medical and long-term care costs. After 8 years of follow up, mean costs were highest for the third trajectory. CONCLUSIONS: The risk of death from cardiovascular disease was higher in the two lower-trajectory groups in cognitive function, and they showed higher healthcare costs during the first 5 years of follow up. After 8 years of follow up, the third trajectory had the highest healthcare costs, perhaps because of hospitalizations attributable to gradual cognitive decline. Geriatr Gerontol Int 2019; 19: 1236-1242.
• The Evaluation of the New Guideline for Assessing Image-Defined Risk Factors in the Low-Risk Protocol (JN-L-10) from the Japan Children's Cancer Group Neuroblastoma Committee

  A. Yoneda, T. Iehara, I. Yokota, H. Takahashi, S. Teramukai, T. Kamijo, A. Nakazawa, T. Takimoto, A. Kikuta, H. Ikeda, A. Nakagawara, T. Tajiri

  PEDIATRIC BLOOD & CANCER 66 S84 - S84 2019年12月 [査読有り][通常論文]
  
• Factors with remission of fatty liver in patients with type 2 diabetes treated with ipragliflozin.

  Yuki Yamauchi, Akinobu Nakamura, Kiyohiko Takahashi, Takahiro Takase, Chiho Yamamoto, Isao Yokota, Tatsuya Atsumi, Hideaki Miyoshi

  Endocrine journal 66 11 995 - 1000 2019年11月28日 [査読有り][通常論文]
   

  We investigated the factors associated with fatty liver remission via treatment with ipragliflozin. The analysis was obtained from our multi-center prospective observational study, including 200 Japanese patients with type 2 diabetes treated with ipragliflozin (50 mg/day) for 24 weeks. The extent of fatty liver was estimated using a fatty liver index (FLI). Based on the FLI after the treatment with ipragliflozin, patients were classified into remission group (FLI < 30) and non-remission group (FLI ≥ 30). After treatment with ipragliflozin for 24 weeks, FLI significantly improved from 64.5 ± 21.6 to 51.9 ± 26.5 (p < 0.01). Body weight, body mass index, waist circumference, aspartate aminotransferase, alanine aminotransferase, and FLI in the remission group were significantly lower compared with those of the non-remission group. Stepwise analysis showed that the baseline FLI (Odds ratio 0.86; 95% confidence interval 0.81-0.90, p < 0.01) was an independent factor associated with FLI remission. Using a receiver operating characteristic (ROC) analysis, the adequate cut-off value for the remission was 50. The area under the ROC curve was 0.93 with the sensitivity and specificity 84.6% and 90.1% respectively. In conclusion, ipragliflozin ameliorated fatty liver. These results suggest that patients with fatty liver with a lower FLI are more likely to attain remission by the treatment with ipragliflozin.
• Clot regression effects of rivaroxaban in the treatment of venous thromboembolism in patients with cancer (CRERIT-VTE cancer): study protocol.

  Shigeki Takai, Naohiko Nakanishi, Isao Yokota, Kojiro Imai, Ayumu Yamada, Takanori Kawasaki, Takashi Okada, Takahisa Sawada, Hiroshi Fujita, Satoaki Matoba

  BMJ open 9 11 e031698  2019年11月05日 [査読有り][通常論文]
   

  INTRODUCTION: Anticoagulant therapy in patients with cancer with venous thromboembolism (VTE) increases the risk of both VTE recurrence and haemorrhagic complication. Direct oral anticoagulants (DOACs) have been shown to be effective in preventing VTE recurrence, and comparable to conventional therapy in preventing VTE recurrence in patients with advanced cancer. Rivaroxaban is a DOAC that causes thrombus regression, possibly through a profibrinolytic effect. Thrombus regression with initial treatment is essential for VTE patients. However, the thrombolytic effect of DOAC for VTE patients with cancer has not been fully examined. Therefore, in this study, we investigate the thrombolytic effect of rivaroxaban in patients with cancer who develop VTE. METHODS AND ANALYSIS: This study is a single-arm, open-label, prospective interventional study. Forty patients aged from 20 to 75 years old at the time of consent who have been diagnosed with acute VTE and have active cancer are included. Patients are excluded if they have received thrombolytic therapy, have creatinine clearance of less than 30 mL/min, have expected a life expectancy of less than 6 months or have deep vein thrombosis limited to the distal lower leg. Eligible patients receive standard treatment with rivaroxaban (15 mg two times daily for 3 weeks, followed by 15 mg QD). The primary study endpoint is clot regression ratio as evaluated by contrast-enhanced CT imaging. CT imaging is obtained at baseline, 21±4 and 90±14 days after the start of rivaroxaban treatment. Secondary endpoints are the recurrence of VTE and haemorrhagic complications. ETHICS AND DISSEMINATION: This study was approved by the institutional review board of the Kyoto Prefectural University of Medicine. Study results will be disseminated through peer-reviewed journals.Trial registration numberUMIN000027793.
• Maximum morning home systolic blood pressure is an indicator of the development of diabetic nephropathy: The KAMOGAWA-HBP study.

  Takuro Okamura, Emi Ushigome, Nobuko Kitagawa, Chikako Oyabu, Toru Tanaka, Goji Hasegawa, Naoto Nakamura, Masayoshi Ohnishi, Sei Tsunoda, Hidetaka Ushigome, Isao Yokota, Masahide Hamaguchi, Mai Asano, Masahiro Yamazaki, Michiaki Fukui

  Journal of diabetes investigation 10 6 1543 - 1549 2019年11月 [査読有り][通常論文]
   

  AIMS/INTRODUCTION: The maximum value of home systolic blood pressure is correlated with damage to target organs, including diabetic nephropathy. However, the precise relationship between the development of diabetic nephropathy and maximum home systolic blood pressure has not been elucidated. MATERIALS AND METHODS: In this prospective 2-year cohort subanalysis of the KAMOGAWA-HBP study, the patient population was 477 Japanese patients with normoalbuminuria. We investigated the effects of mean and maximum home blood pressure on the development of diabetic nephropathy, which we defined as a urinary albumin excretion value ≥30 mg/g creatinine. Among the 477 patients, 67 developed diabetic nephropathy. RESULTS: In our multivariate logistic regression analyses, the maximum morning home systolic blood pressure was significantly positively associated with the development of diabetic nephropathy after adjusting for patient sex and age, smoking status, the diabetes mellitus duration, body mass index, creatinine, total cholesterol, hemoglobin A1c, and antihypertensive medication use (odds ratio 1.21, 95% confidence interval 1.03-1.42, P = 0.021). CONCLUSIONS: Maximum home blood pressure can be identified at a glance, and its measurement would thus be helpful to healthcare providers who treat patients with diabetes and normoalbuminuria.
• Home blood pressure is associated with cognitive impairment among elderly patients with type 2 diabetes: KAMOGAWA-HBP study.

  Keiko Iwai, Emi Ushigome, Shinobu Matsumoto, Nobuko Kitagawa, Hidetaka Ushigome, Isao Yokota, Mai Asano, Masahide Hamaguchi, Masahiro Yamazaki, Michiaki Fukui

  Diabetes & vascular disease research 16 6 506 - 512 2019年11月 [査読有り][通常論文]
   

  BACKGROUND: This cross-sectional study was designed to examine the association between home blood pressure and cognitive impairment in elderly patients with type 2 diabetes. METHODS: Home blood pressure was measured in the morning and evening for 14 consecutive days in 749 patients with type 2 diabetes. A total of 231 patients were included in the study population. Cognitive function was evaluated using the Mini-Cog test, which is used as a screening for cognitive impairment in elderly patients. We performed a logistic regression analysis and measured the area under the receiver operating characteristic curve and estimated home blood pressure as a marker of cognitive impairment. RESULTS: The adjusted odds ratio (95% confidence interval) of evening systolic blood pressure for cognitive impairment was 1.24 (1.02-1.53). Evening systolic blood pressure showed the highest area under the receiver operating characteristic curve for cognitive impairment in both unadjusted and adjusted models. In all subgroup analyses except gender, home blood pressure showed higher area under the receiver operating characteristic curve than clinic blood pressure. CONCLUSION: Home blood pressure was associated with cognitive impairment in elderly patients with type 2 diabetes.
• Results of a prospective clinical trial JN-L-10 using image-defined risk factors to inform surgical decisions for children with low-risk neuroblastoma disease: A report from the Japan Children's Cancer Group Neuroblastoma Committee.

  Tomoko Iehara, Akihiro Yoneda, Isao Yokota, Hideto Takahashi, Satoshi Teramukai, Takehiko Kamijyo, Atsuko Nakazawa, Tetsuya Takimoto, Atsushi Kikuta, Shigeki Yagyu, Hitoshi Ikeda, Akira Nakagawara, Tatsuro Tajiri

  Pediatric blood & cancer 66 11 e27914  2019年11月 [査読有り][通常論文]
   

  BACKGROUND: The present study sought to reduce the incidence of treatment complications of low-risk neuroblastoma by using image-defined risk factors (IDRFs) to inform the timing of surgical resection. PROCEDURES: Eligible patients included children (<18 years of age) with stage 1 or 2 disease, children (<365 days of age) with stage 3 disease, and infants with stage 4S disease. In IDRF-negative cases, treatment was completed with surgical resection alone. In IDRF-positive cases, the timing of surgery was determined based on the IDRFs after low-dose chemotherapy with 2-3 of the following four drugs: vincristine, cyclophosphamide, pirarubicin, and carboplatin. The outcome measures were overall survival, progression-free survival, and adverse events. This study was registered with the UMIN Clinical Trials Registry (number 000004355). RESULTS: Of the 60 patients screened between 2010 and 2013, 58 eligible patients were enrolled; 32 were identified as IDRF negative at diagnosis while 26 were identified as IDRF positive and underwent induction chemotherapy. The 3-year overall and progression-free survival rates of the 58 patients were 100% and 82.8% (95% confidence interval: 70.3-90.3), respectively. Neutropenia was the most frequently reported grade 3 or 4 chemotherapy-related form of toxicity (41.7%). With regard to surgical complications, 2.5% of all patients developed pleural effusion and ascites as early complications, while only 2.5% developed renal atrophy as a long-term complication. No fatal toxicities were observed. CONCLUSION: Using IDRFs to inform surgical decision making for the treatment of low-risk neuroblastoma improved prognosis and reduced the incidence of long-term complications.
• Effects of dietary salt restriction on home blood pressure in diabetic patients with excessive salt intake: a pilot study.

  Emi Ushigome, Chikako Oyabu, Keiko Iwai, Nobuko Kitagawa, Aya Kitae, Tomonori Kimura, Isao Yokota, Hidetaka Ushigome, Masahide Hamaguchi, Mai Asano, Masahiro Yamazaki, Michiaki Fukui

  Journal of clinical biochemistry and nutrition 65 3 252 - 257 2019年11月 [査読有り][通常論文]
   

  The aim of the present study was to examine whether dietary salt restriction guidance is beneficial for dietary salt restriction and lowering of home blood pressure in patients with diabetes with excessive salt intake. We performed an intervention trial of 37 people with type 2 diabetes and excessive salt intake. National registered dietitians provided dietary salt restriction guidance to each patient at the start of the study. All participants were instructed to perform triplicate morning and evening home blood pressure measurements using home blood pressure telemonitoring system. Daily salt intake at 2 months and 6 months was significantly lower than that at baseline; the difference was 0.8 [95% confidence interval (CI): 0.2-1.4, p = 0.009] g and 0.7 (95% CI: 0.1-1.3, p = 0.009) g, respectively. Morning systolic blood pressure at 2 months and 6 months was significantly lower than that at baseline; the difference was 2.7 (95% CI: 0.2-5.1, p = 0.034) mmHg and 5.8 (95% CI: 0.5-11.1, p = 0.034) mmHg, respectively. This intervention study revealed, for the first time, that dietary salt restriction guidance provided by a national registered dietitian is beneficial for reducing daily salt intake and home blood pressure in people with diabetes with excessive salt intake.
• Residual Cancer Volume Predicts Clinical Outcome in Patients With Esophageal Squamous Cell Carcinoma After Neoadjuvant Chemotherapy.

  Ryuta Nakao, Eiichi Konishi, Hitoshi Fujiwara, Eigo Otsuji, Isao Yokota, Yoji Urata, Akio Yanagisawa

  International journal of surgical pathology 27 7 713 - 721 2019年10月 [査読有り][通常論文]
   

  Background. The aim of this study was to assess the prognostic significance of residual cancer volume (RCV) in patients with esophageal squamous cell carcinoma (ESCC) who received esophagectomy after neoadjuvant chemotherapy. Methods. We measured RCV by using complete stepwise sections at 6- to 8-mm intervals obtained from 81 ESCC patients with clinical stages IB to III. RCV was defined as the summation of all products of residual cancer area and thickness, and its cutoff value was set by receiver operator characteristic curve analysis on 3-year disease-specific survival (DSS). The multivariate analyses were performed in comparison with histopathological factors including tumor regression grades according to the Japanese Classification of Esophageal Cancer (TRG-JPN) or reported by Becker et al (TRG-Becker). Results. The range of RCV was 0 to 49.3 cm3 (median = 1.4 cm3), and the cutoff value was set at 1.0 cm3 (sensitivity = 78%; specificity = 68%). In the Kaplan-Meier curve analysis with the log-rank test, RCV > 1.0 cm3 predicted poorer prognosis for relapse-free survival (RFS; 5-year RFS rate, 12% vs 47%; P < .001) and DSS (5-year DSS rate, 27% vs 61%; P < .001). The multivariate analyses by the Cox hazards model revealed that RCV > 1.0 cm3 was a factor predicting poor prognosis for RFS (P = .013; hazard ratios [HR] = 2.62) and DSS (P = .028; HR = 2.56) compared with histopathological factors including TRG-JPN; RFS (P = .014; HR = 3.03) and DSS (P = .045; HR = 2.71) compared with histopathological factors including TRG-Becker. Conclusions. The study suggested that determining RCV is a new method of predicting prognosis in ESCC patients after neoadjuvant chemotherapy.
• Gender differences in occurrence of behavioral and emotional problems at the lower grades of elementary school: Association with developmental and behavioral characteristics at 5 years.

  Zen Y, Chiyonobu T, Yuge M, Yokota I, Morimoto M, Teramukai S, Hosoi H

  Brain & development 41 9 760 - 768 2019年10月 [査読有り][通常論文]
   

  AIM: We examined whether developmental status and behavioral problems at age five were related to the occurrence of behavioral and emotional problems in the lower grades of elementary school among non-clinical children who did not receive specialized support for developmental problems in early childhood. METHODS: The participants were 367 (non-clinical: 325) second- and third-grade elementary school children. The mean age at follow-up was 7.63 (SD = 0.62). Parents completed a questionnaire about their children's developmental status and behavioral problems during a community health check-up for 5-year-olds. Behavioral and emotional problems at school age were assessed using the Strengths and Difficulties Questionnaire (SDQ). The association between developmental and behavioral characteristics at age five and each of the SDQ subscales at school age was analyzed with logistic regression. RESULTS: Hyperactivity/inattention, conduct problems, and emotional problems at school age were associated with developmental and behavioral factors in 5-year-olds. The problem of hyperactivity/inattention at school age was associated with hyperactivity/inattention in both genders, and significant gender differences were identified. The relationship with hyperactivity at the age of five was significant for boys, whereas the relationship with inattention was only significant for girls. Emotional problems were significantly associated with social behaviors and developmental status at five years of age only in girls. CONCLUSIONS: It is necessary for clinicians and teachers to consider the relation of developmental and behavioral characteristics to the background of behavioral and emotional problems at school age and to be aware of gender differences.
• Utility of Coagulation Markers for the Prediction of Rapidly Progressive Interstitial Lung Disease in Patients with Dermatomyositis.

  Tomoya Sagawa, Takashi Kida, Tohru Inaba, Isao Yokota, Risa Sagawa, Akiko Kasahara, Shunya Kaneshita, Takuya Inoue, Hidetake Nagahara, Kazuki Fujioka, Makoto Wada, Masataka Kohno, Yutaka Kawahito

  Lung 197 4 437 - 442 2019年08月 [査読有り][通常論文]
   

  We aimed to evaluate the utility of coagulation markers for the prediction of rapidly progressive interstitial lung disease (RP-ILD) in patients with dermatomyositis (DM). In this retrospective study, 29 patients with DM-associated ILD were analyzed. The number of patients with RP-ILD was 15 (52%). The baseline clinical and demographic data and laboratory markers were analyzed to identify predictive factors for RP-ILD.The univariate logistic regression analysis demonstrated that in addition to well-known laboratory markers, such as serum ferritin, KL-6, and lymphocyte counts, a prolonged activated partial thromboplastin time (aPTT) ratio at the time of DM-associated ILD diagnosis was useful for predicting RP-ILD. Moreover, the logistic regression model and receiver operating characteristic curve analysis showed that combinations of the aPTT ratio and well-known laboratory markers were significantly effective in predicting RP-ILD. This study suggested that an association between RP-ILD and the coagulation system exists.
• Efficacy of denosumab for restoring normal bone mineral density in women receiving adjuvant aromatase inhibitors for early breast cancer.

  Koichi Sakaguchi, Hisako Ono, Katsuhiko Nakatsukasa, Takashi Ishikawa, Yoshie Hasegawa, Masato Takahashi, Naoki Niikura, Kei Koizumi, Teruhisa Sakurai, Hideo Shigematsu, Shunji Takahashi, Shinichiro Taira, Masato Suzuki, Kazutaka Narui, Daishu Miura, Kimito Yamada, Mana Yoshimura, Hisashi Shioya, Eiichi Konishi, Yokota Isao, Kojiro Imai, Kei Fujikawa, Tetsuya Taguchi

  Medicine 98 32 e16770  2019年08月 [査読有り][通常論文]
   

  BACKGROUND: Osteoporosis is a major side effect of aromatase inhibitors (AIs), which are greatly effective in the treatment of breast cancer. However, there are no satisfactory measures against osteoporosis. In this multicenter, randomized, comparative study, we evaluate the efficacy of denosumab for preventing loss of bone mineral density (BMD) induced by adjuvant therapy with AI s in breast cancer patients with normal BMD. PATIENTS AND METHODS: The bone loss-suppressing effect of denosumab will be comparatively evaluated in postmenopausal patients scheduled to receive letrozole or anastrozole as a postoperative endocrine therapy for stage I-IIIA hormone-sensitive breast cancer and a control group. Patients will be administered letrozole 2.5 mg or anastrozole 1 mg once a day, and the treatment will be continued for 5 years unless recurrence, secondary cancer, or unacceptable toxicity develops. Patients in the denosumab group will receive a subcutaneous injection of 60 mg of denosumab every 6 months. The primary endpoint is the rate of change in the lumbar spine (L1-L4) BMD, as determined by dual-energy X-ray absorptiometry (DXA), 12 months after the start of the injection. The secondary endpoints were ETHICS AND DISSEMINATION:: The protocol was approved by the institutional review boards of Kyoto Prefectural University of Medicine and all the participating faculties. Written informed consent was obtained from all patients before registration, in accordance with the Declaration of Helsinki. Results of the study will be disseminated via publications in peer-reviewed journals. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT03324932, Japan Registry of Clinical Trial (jRCT): CRB5180001.
• Age estimation based on visual parameters of the skin of cadavers.

  Hajime Tsuboi, Isao Yokota, Daisuke Miyamori, Yoshihisa Akasaka, Ayumu Yamada, Hiroshi Ikegaya

  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) 25 4 532 - 537 2019年07月 [査読有り][通常論文]
   

  BACKGROUND: Previous studies have reported relationships between various visual parameters of the skin and changes due to aging. Due to an increase in the discovery of unidentified bodies, the field of forensic medicine anticipates the development of a rapid method for estimating age. The present study measured various visual parameters of the skin in human remains and investigated the correlation between these parameters and age. MATERIALS AND METHODS: Skin images were taken of four body parts (cheek, chin, brachium, and thigh) of 414 forensic cases. We interpreted eight visual parameters of the skin (smoothness, roughness, texture, dullness, brightness, erythema, color phase, and sagging) from skin photograph images, and constructed three age-prediction models, categorized by sex, postmortem interval, and age. RESULTS: Significant correlations were observed in the erythema of the cheek and chin, the roughness of the brachium, and the texture of the brachium and thigh among the visual parameters calculated in four body parts, using the three models. The root-mean-square errors, which indicate the precision of the three prediction models, were 13.06, 13.80, and 13.77. The only model that demonstrated a correlation with the visual parameters was sex (but not age or postmortem interval). CONCLUSION: Similar to living subjects, we observed a correlation with age for a number of visual parameters. The parameters that correlate with age depend on whether the site being measured was exposed to sunlight. Age estimation based on visual parameters requires measurement of visual parameters for skin both exposed and not exposed to sunlight.
• Risk Factors for Polypharmacy in Elderly Patients With Cancer Pain.

  Kayoko Morio, Isseki Maeda, Isao Yokota, Kazuyuki Niki, Taizo Murata, Yasushi Matsumura, Etsuko Uejima

  The American journal of hospice & palliative care 36 7 598 - 602 2019年07月 [査読有り][通常論文]
   

  OBJECTIVE: Polypharmacy (PP) is a burden in elderly patients with cancer pain; however, risk factors for PP remain unclear. The purpose of this study was to investigate the risk factors for PP in this patient population. METHODS: We retrospectively reviewed the medical charts of patients aged ≥65 years with cancer pain who were treated at Osaka University Hospital between February 2014 and June 2016 according to the World Health Organization 3-step ladder for cancer pain relief. We defined PP as ≥5 medications and conducted exploratory research to examine the association between PP and patient characteristics. Performance status (PS) was estimated according to the Eastern Cooperative Oncology Group system and is categorized as good PS (0-1) and poor PS (2-4). RESULTS: We reviewed 206 patients (122 men and 84 women) with a median age of 71 years (range, 65-89 years) and found that 174 patients (84.5%) had PP. In multivariate logistic analysis, PP was significantly associated with an increased number of comorbidities (odds ratio [OR]: 4.93, 95% confidence interval [CI], 2.57-11.42, P < .001), poor PS (OR: 4.50, 95% CI, 1.06-31.68, P = .039), and administration of an anticancer or molecular targeted drug (OR: 2.78, 95% CI, 1.13-7.16, P = .025). CONCLUSIONS: An increased number of comorbidities, poor PS, and administration of an anticancer or molecular targeted drug were considered risk factors for PP in elderly patients with cancer pain. Sharing these risk factors with medical staff will help reduce the occurrence of problems associated with PP.
• Rapid weight loss with dietary salt restriction in hospitalized patients with chronic kidney disease.

  Yu Mihara, Hiroshi Kado, Isao Yokota, Yayoi Shiotsu, Kazuhiro Sonomura, Tetsuro Kusaba, Tsuguru Hatta, Satoaki Matoba, Keiichi Tamagaki

  Scientific reports 9 1 8787 - 8787 2019年06月19日 [査読有り][通常論文]
   

  Dietary salt restriction is essential for managing fluid retention in patients with chronic kidney disease (CKD). In this retrospective cohort study, we investigated weight loss from the perspective of fluid status in CKD patients during a 7-day hospitalization period while consuming a low-salt diet (5 g/day). Among 311 patients, the median weight loss (interquartile range, maximum) was 0.7 (0.0-1.4, 4.7) kg on Day 4 and 1.0 (0.3-1.7, 5.9) kg on Day 7. Patients were classified into quartiles based on pre-hospital urinary salt excretion (quartile [Q] 1, 1.2-5.7; Q2, 5.8-8.4; Q3, 8.5-11.3; Q4, 11.4-29.2 g/day). Weight loss was significantly greater in Q3 and Q4 than in Q1. The body mass index (BMI) and urinary salt excretion in the first 24 hours after admission were independently associated with rapid weight loss on Day 4 by multivariate logistic regression analysis. In conclusion, CKD patients with a high salt intake or high BMI exhibit rapid weight loss within a few days of consuming a low-salt diet. Dietary salt restriction is effective for reducing proteinuria in these patients, but long-term observation is needed to confirm the sustained effects.
• Objective evaluation of fat tissue induration after breast reconstruction using a deep inferior epigastric perforator (DIEP) flap.

  Yoshihiro Sowa, Isao Yokota, Kei Fujikawa, Daiki Morita, Tetsuya Taguchi, Toshiaki Numajiri

  Journal of plastic surgery and hand surgery 53 3 125 - 129 2019年06月 [査読有り][通常論文]
   

  Problems in breast reconstruction with deep inferior epigastric perforator (DIEP) flaps include postoperative fat induration and necrosis. A resulting clinical symptom is palpable indurated tissue, but it is difficult to measure the stiffness of transplanted fat tissues objectively at a deep site. The ability to perform shear-wave elastography (SWE) was recently added to some common ultrasonic echo devices, enabling objective three-dimensional measurements of tissue stiffness. In this study, we measured the stiffness of transplanted DIEP flaps using SWE to examine the effects of measurement sites, flap size and perforator patterns on stiffness. The subjects were 26 patients who showed induration of a transplanted flap on palpation in follow-up observation performed more than 6 months after breast reconstruction with a DIEP flap. The effects of the weight of the transplanted flap, and the diameter, number and location of the perforators on the stiffness of fat tissue were also analyzed. Within each zone, distal regions showed higher values, but in Zone II, significantly higher stiffness was also found in the proximal region. Multivariate regression analysis including all measurement sites, the weight of transplanted flap, and diameter, number and location of perforators showed that the stiffness of fat tissue was significantly higher in subjects with a larger weight flap. For safe reconstruction, it will be useful to examine the stiffness of fat tissue in individual regions of a transplanted flap retrospectively, because the examination results can be used in actual clinical practice.
• Association of low back pain with presenteeism in hospital nursing staff.

  Junpei Yokota, Naoto Fukutani, Kazuko Nin, Hiroe Yamanaka, Makoto Yasuda, Yuto Tashiro, Tomofumi Matsushita, Yusuke Suzuki, Isao Yokota, Satoshi Teramukai, Tomoki Aoyama

  Journal of occupational health 61 3 219 - 226 2019年05月 [査読有り][通常論文]
   

  OBJECTIVES: Chronic low back pain (LBP) is known to cause various disorders compared with acute LBP. However, there was no study evaluating presenteeism due to LBP divided into subcategories by the duration of LBP. Therefore, this study aims to investigate the relationship between acute or chronic LBP and presenteeism in hospital nursing staff. METHODS: Overall, 1100 nurses filled in a questionnaire on basic attributes, LBP symptoms, depression symptoms, and work productivity. The subjects were divided into three groups based on the period of LBP and the compared work productivity. Work Limitation Questionnaire Japanese version (WLQ-J) was used for the assessment of work productivity. The effects of acute and chronic LBP on presenteeism were evaluated through multiple regression analysis models. RESULTS: In total, 765 subjects, without missing values, were included. The overall prevalence of LBP was 64.6% (acute LBP 47.5%, chronic LBP 17.1%). On multiple regression analysis, acute pain and presenteeism were not associated. Conversely, chronic LBP was associated with time management (adjusted β = -2.3, 95% CI: -4.5 to -1.1), mental-interpersonal relationship (adjusted β = -2.8, 95% CI: -5.1 to -0.6), and output (adjusted β = -2.7, 95% CI: -5.4 to 0.0) after adjustment for sex and career years. When depression was included in the adjustment factors, chronic LBP and WLQ subscales were not associated. CONCLUSIONS: It became obvious that Chronic LBP in nurses was significantly related to time management, mental-interpersonal relationship, and output. The importance of preventing a decline in work productivity by taking precautions to prevent chronic LBP and depression was suggested.
• Promoting a nursing team's ability to notice intent to communicate in lightly sedated mechanically ventilated patients in an intensive care unit: An action research study.

  Ayako Noguchi, Tomoko Inoue, Isao Yokota

  Intensive & critical care nursing 51 64 - 72 2019年04月 [査読有り][通常論文]
   

  OBJECTIVES: This study aimed to examine changes in the practice of nurses who received an intervention designed to increase their awareness of endotracheally intubated, lightly sedated mechanically ventilated patients' intent to communicate. RESEARCH METHODOLOGY: Action research was applied. Specifically, three interventions promoting awareness of patients' intent to communicate were administered and pre- and post-intervention, observations of patient-nurse interactions, unstructured interviews with nurses and a patients' satisfaction survey were conducted. The pre- and post-intervention patient-nurse interactions and patients' survey results were then compared and a content analysis of the interviews and field notes was performed. SETTING: The intensive care unit of a university hospital. MAIN OUTCOME MEASURE: Nurses' awareness of lightly sedated mechanically ventilated patients' intent to communicate. FINDINGS: After the intervention, the incidence-rate ratios for nurses noticing of patients' intent to communicate were 1.53; there was no change in the frequency of patients' intent to communicate. Further, nurses became more aware of and reflected on their own practices, showed increased interest in co-workers' practices and considered their actions from patients' perspectives. Patients' satisfaction with nurses' respect for their wishes and dignity also increased. CONCLUSIONS: Action research can induce a change in intensive-care-unit-based nursing practice towards patient-centred care.
• Dynamic prediction of repeated events data based on landmarking model: application to colorectal liver metastases data.

  Isao Yokota, Yutaka Matsuyama

  BMC medical research methodology 19 1 31 - 31 2019年02月14日 [査読有り][通常論文]
   

  BACKGROUND: In some clinical situations, patients experience repeated events of the same type. Among these, cancer recurrences can result in terminal events such as death. Therefore, here we dynamically predicted the risks of repeated and terminal events given longitudinal histories observed before prediction time using dynamic pseudo-observations (DPOs) in a landmarking model. METHODS: The proposed DPOs were calculated using Aalen-Johansen estimator for the event processes described in the multi-state model. Furthermore, in the absence of a terminal event, a more convenient approach without matrix operation was described using the ordering of repeated events. Finally, generalized estimating equations were used to calculate probabilities of repeated and terminal events, which were treated as multinomial outcomes. RESULTS: Simulation studies were conducted to assess bias and investigate the efficiency of the proposed DPOs in a finite sample. Little bias was detected in DPOs even under relatively heavy censoring, and the method was applied to data from patients with colorectal liver metastases. CONCLUSIONS: The proposed method enabled intuitive interpretations of terminal event settings.
• Usefulness of urinary trypsinogen-2 and trypsinogen activation peptide in acute pancreatitis: A multicenter study in Japan.

  Hiroaki Yasuda, Keisho Kataoka, Yoshifumi Takeyama, Kazunori Takeda, Tetsuhide Ito, Toshihiko Mayumi, Shuji Isaji, Tetsuya Mine, Motoji Kitagawa, Seiki Kiriyama, Junichi Sakagami, Atsushi Masamune, Kazuo Inui, Kenji Hirano, Ryukichi Akashi, Masamichi Yokoe, Yoshio Sogame, Kazuichi Okazaki, Chie Morioka, Yasuyuki Kihara, Shigeyuki Kawa, Masao Tanaka, Akira Andoh, Wataru Kimura, Isao Nishimori, Junji Furuse, Isao Yokota, Tooru Shimosegawa

  World journal of gastroenterology 25 1 107 - 117 2019年01月07日 [査読有り][通常論文]
   

  BACKGROUND: Rapid urinary trypsinogen-2 dipstick test and levels of urinary trypsinogen-2 and trypsinogen activation peptide (TAP) concentration have been reported as prognostic markers for the diagnosis of acute pancreatitis. AIM: To reconfirm the validity of all these markers in the diagnosis of acute pancreatitis by undertaking a multi-center study in Japan. METHODS: Patients with acute abdominal pain were recruited from 17 medical institutions in Japan from April 2009 to December 2012. Urinary and serum samples were collected twice, at enrollment and on the following day for measuring target markers. The diagnosis and severity assessment of acute pancreatitis were assessed based on prognostic factors and computed tomography (CT) Grade of the Japanese Ministry of Health, Labour, and Welfare criteria. RESULTS: A total of 94 patients were enrolled during the study period. The trypsinogen-2 dipstick test was positive in 57 of 78 patients with acute pancreatitis (sensitivity, 73.1%) and in 6 of 16 patients with abdominal pain but without any evidence of acute pancreatitis (specificity, 62.5%). The area under the curve (AUC) score of urinary trypsinogen-2 according to prognostic factors was 0.704, which was highest in all parameter. The AUC scores of urinary trypsinogen-2 and TAP according to CT Grade were 0.701 and 0.692, respectively, which shows higher than other pancreatic enzymes. The levels of urinary trypsinogen-2 and TAP were significantly higher in patients with extended extra-pancreatic inflammation as evaluated by CT Grade. CONCLUSION: We reconfirmed urinary trypsinogen-2 dipstick test is useful as a marker for the diagnosis of acute pancreatitis. Urinary trypsinogen-2 and TAP may be considered as useful markers to determine extra-pancreatic inflammation in acute pancreatitis.
• Plasma neurofilament light chain: A potential prognostic biomarker of dementia in adult Down syndrome patients.

  Makiko Shinomoto, Takashi Kasai, Harutsugu Tatebe, Masaki Kondo, Takuma Ohmichi, Masafumi Morimoto, Tomohiro Chiyonobu, Naoto Terada, David Allsop, Isao Yokota, Toshiki Mizuno, Takahiko Tokuda

  PloS one 14 4 e0211575  2019年 [査読有り][通常論文]
   

  People with Down syndrome (DS) are at high risk of developing Alzheimer disease (AD) with aging. The diagnosis and treatment trials are hampered by a lack of reliable blood biomarkers. Plasma neurofilament light chain (NfL) is one of the established biomarkers of AD, suggesting that it may be useful as an indicator of dementia in DS patients. The aims of this study were: 1) to examine whether plasma levels of NfL in DS patients are correlated with decreased adaptive behavior scores one year after sample collection, and 2) to compare plasma levels of NfL in adults with DS and an age-matched healthy control population. In this study, plasma levels of NfL in 24 patients with DS and 24 control participants were measured by the single-molecule immunoarray (Simoa) method. We observed significantly increased plasma NfL levels in the DS compared with the control group. There was a significant correlation between age and levels of plasma NfL in both groups. This age-dependent elevation was steeper in the DS compared with the control group. Moreover, elevated plasma NfL was associated with decreased adaptive behavior scores one year later, after age-adjustment. Previously reported blood-based biomarkers available in Simoa for DS, plasma total tau and phosphorylated tau, were not significantly correlated with the annual decrement of adaptive behavior scores after age-adjustment. These results suggest that plasma NfL has the potential to serve as an objective biomarker to predict dementia in adult DS patients.
• Albumin and Hemoglobin Trajectories and Incident Disabling Dementia in Community-Dwelling Older Japanese.

  Yu Taniguchi, Akihiko Kitamura, Sho Kaito, Yuri Yokoyama, Isao Yokota, Tomohiro Shinozaki, Satoshi Seino, Hiroshi Murayama, Yutaka Matsuyama, Tomoko Ikeuchi, Yoshinori Fujiwara, Shoji Shinkai

  Dementia and geriatric cognitive disorders 47 4-6 233 - 242 2019年 [査読有り][通常論文]
   

  BACKGROUND: Serum albumin and hemoglobin levels are independently associated with subsequent cognitive deterioration in older adults. This prospective study used repeated measures analysis to identify aging trajectories in serum albumin and hemoglobin levels and investigated if these trajectories were associated with incident disabling dementia among community-dwelling older Japanese. METHODS: A total of 2,005 adults aged 65-90 years participated in annual geriatric health assessments during the period from June 2002 through July 2017; the total number of observations was 9,330. A review of a municipal database of the Japanese public long-term care insurance system identified 1,999 of 2,005 adults without dementia at baseline, 278 (13.9%) of whom developed disabling dementia during the follow-up period (June 2002 through December 2017). RESULTS: We identified three trajectory patterns (high, moderate, and low) for serum albumin and hemoglobin levels for the age period 65 through 90 years. After controlling for potential confounders, participants with moderate and low trajectories for serum albumin level had hazard ratios of 1.27 (95% confidence interval 0.94-1.72) and 2.07 (1.37-3.11), respectively, for the development of incident disabling dementia, with the high trajectory group as reference. The respective hazard ratios for hemoglobin level were 1.31 (0.93-1.85) and 1.58 (1.04-2.40), respectively. CONCLUSION: Dementia risk was higher for individuals with low trajectories for serum albumin and hemoglobin levels. This finding highlights the importance of interventions that improve nutritional status and control relevant diseases in middle-aged and older adults with low serum albumin and hemoglobin levels.
• Reduction of the rocuronium-induced withdrawal reflex by MR13A10A, a generic rocuronium with a novel solution: A randomized, controlled study.

  Masaru Shimizu, Fumimasa Amaya, Mao Kinoshita, Masaki Yamasaki, Isao Yokota, Teiji Sawa

  PloS one 14 10 e0223947  2019年 [査読有り][通常論文]
   

  BACKGROUND: Rocuronium induces venous pain and the withdrawal reflex during injection. MR13A10A, generic rocuronium with a novel solution, reduced the injection-induced withdrawal reflex in rodents. We hypothesized that MR13A10A would reduce the frequency and severity of injection-induced withdrawal reflexes compared with original rocuronium during clinical anesthesia induction. METHODS: This prospective, open (but assessor-blinded), randomized, controlled study was conducted at a single academic hospital. The assessor was blinded to the study condition in order to minimize observer bias. Participants were allocated to either MR13A10A or traditional formula groups by a blocked stratified randomization method. Participants in the MR13A10A group received MR13A10A, whereas the original rocuronium group received the same amount of original rocuronium. The primary outcome was presence of the withdrawal reflex after rocuronium injection. Severity of the withdrawal reflex, changes in blood pressure and heart rate, and the train of four (TOF) ratio were measured as secondary outcomes. The withdrawal reflex was assessed using a video recording in a blinded manner. RESULTS: Of the 149 participants, 76 were allocated to the MR13A10A group and 73 to the original rocuronium group. The frequency of the withdrawal reflex was significantly lower with MR13A10A compared with original rocuronium (19.7% and 54.8% for MR13A10A and original rocuronium groups, respectively, p<0.001). The odds ratio adjusted for cannulation site, cannula size, induction agent and age was 6.27 (95% CI, 2.87, 13.73 p<0.001). Original rocuronium was an independent factor related to a higher post-treatment heart rate. The proportions of TOF ratios = 0 were similar between the two groups. CONCLUSION: The frequency and severity of the withdrawal reflex after injection were significantly reduced by using MR13A10A. MR13A10A might contribute to safe and less invasive anesthesia management.
• Prospective analysis of the association between skeletal-related events and quality of life in patients with advanced lung cancer (CSP-HOR13).

  Hiroshi Kunikane, Isao Yokota, Nobuyuki Katakami, Koji Takeda, Koichi Takayama, Toshiyuki Sawa, Hiroshi Saito, Masao Harada, Soichiro Yokota, Kiyoshi Ando, Yuko Saito, Yasuo Ohashi, Kenji Eguchi

  Oncology letters 17 1 1320 - 1326 2019年01月 [査読有り][通常論文]
   

  A prospective study has previously reported on the incidence of bone metastasis (BM) and skeletal-related events (SREs) in patients with advanced lung cancer. The aim of the present study was to prospectively investigate how the quality of life (QOL) of patients with advanced lung cancer was affected by SREs. Patients with stage IIIB or IV non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) at any stage were followed up every four weeks to determine if they had developed SREs. QOL questionnaires were conducted at enrollment, at 3- and 12-months later and at 1 month after the onset of SREs, using QOL scores including the EuroQOL-5 Dimension (EQ-5D), Functional Assessment of Cancer Therapy-General (FACT-G) and activities of daily living (ADL) scores obtained by the Barthel Index. A total of 274 patients were enrolled in the study. At enrollment the EQ-5D and Barthel Index scores were lower in patients with SREs compared with patients without SREs. A chronological analysis revealed no statistically significant changes in either QOL or ADL in any of the patients. For 14 patients in whom QOL data was collected following the onset of SREs, the evaluation undertaken on the four subscales of the FACT-G revealed a significant decline in emotional functioning following the onset of SREs.
• A comparison of the resection rate for cold and hot snare polypectomy for 4-9 mm colorectal polyps: a multicentre randomised controlled trial (CRESCENT study).

  Takuji Kawamura, Yoji Takeuchi, Satoshi Asai, Isao Yokota, Eisuke Akamine, Minoru Kato, Takuji Akamatsu, Kazuhiro Tada, Yoriaki Komeda, Mineo Iwatate, Ken Kawakami, Michiko Nishikawa, Daisuke Watanabe, Atsushi Yamauchi, Norimasa Fukata, Masaaki Shimatani, Makoto Ooi, Koichi Fujita, Yasushi Sano, Hiroshi Kashida, Satoru Hirose, Hiroyoshi Iwagami, Noriya Uedo, Satoshi Teramukai, Kiyohito Tanaka

  Gut 67 11 1950 - 1957 2018年11月 [査読有り][通常論文]
   

  OBJECTIVE: To investigate the success rate of cold snare polypectomy (CSP) for complete resection of 4-9 mm colorectal adenomatous polyps compared with that of hot snare polypectomy (HSP). DESIGN: A prospective, multicentre, randomised controlled, parallel, non-inferiority trial conducted in 12 Japanese endoscopy units. Endoscopically diagnosed sessile adenomatous polyps, 4-9 mm in size, were randomly assigned to the CSP or HSP group. After complete removal of the polyp using the allocated technique, biopsy specimens from the resection margin after polypectomy were obtained. The primary endpoint was the complete resection rate, defined as no evidence of adenomatous tissue in the biopsied specimens, among all pathologically confirmed adenomatous polyps. RESULTS: A total of 796 eligible polyps were detected in 538 of 912 patients screened for eligibility between September 2015 and August 2016. The complete resection rate for CSP was 98.2% compared with 97.4% for HSP. The non-inferiority of CSP for complete resection compared with HSP was confirmed by the +0.8% (90% CI -1.0 to 2.7) complete resection rate (non-inferiority p<0.0001). Postoperative bleeding requiring endoscopic haemostasis occurred only in the HSP group (0.5%, 2 of 402 polyps). CONCLUSIONS: The complete resection rate for CSP is not inferior to that for HSP. CSP can be one of the standard techniques for 4-9 mm colorectal polyps. (Study registration: UMIN000018328).
• Impact of right ventricular volume and function evaluated using cardiovascular magnetic resonance imaging on outcomes after surgical ventricular reconstruction.

  Yamazaki S, Numata S, Inoue T, Itatani K, Morimoto K, Ohira S, Manabe K, Yokota I, Yaku H

  European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery 54 5 867 - 874 2018年11月 [査読有り][通常論文]
   

  OBJECTIVES: This study aimed to evaluate whether cardiac magnetic resonance imaging (MRI)-derived right ventricular (RV) assessment can facilitate risk stratification among patients with ischaemic cardiomyopathy who underwent surgical ventricular reconstruction (SVR). METHODS: We retrospectively analysed 53 patients who underwent SVR. The patients were preoperatively evaluated using cardiac MRI. Cine-MRI was acquired for left ventricular (LV) and RV volume. Gadolinium-enhanced MRI was performed to evaluate LV scarring. The mid-term (median, 58 months) risk factors of all-cause mortality and major adverse cardiac events were analysed. RESULTS: A significant reduction in LV end-diastolic and end-systolic volume index and an increase in LV ejection fraction were observed early after SVR. RV end-diastolic volume index (RVEDVI) and RV end-systolic volume index (RVESVI) decreased after SVR (preoperative versus postoperative: RVEDVI, 71 ± 24 vs 62 ± 17 ml/m2, P = 0.006; RVESVI, 44 ± 26 vs 37 ± 16 ml/m2, P = 0.033), but RV ejection fraction did not change (preoperative versus postoperative: RV ejection fraction 40.8±14.6 vs 42.0±11.0%, P = 0.067). At follow-up, 25 deaths and 31 major adverse cardiac events occurred. After adjustment for age, creatinine level and preoperative mitral regurgitation grade, the Cox-hazard model indicated that RVEDVI [P = 0.006, hazard ratio (HR) 1.03, 95% confidence interval (CI) 1.01-1.05] and RVESVI [P = 0.007, HR 1.02, 95% CI 1.01-1.04] were significant predictors for all-cause mortality. As for major adverse cardiac events, RVEDVI (P = 0.007, HR 1.03, 95% CI 1.01-1.05), RVESVI (P = 0.002, HR 1.03, 95% CI 1.01-1.04) and RV ejection fraction (P = 0.018, HR 0.97, 95% CI 0.94-0.99) were significant. CONCLUSIONS: RV parameters were more sensitive than LV parameters for predicting worse outcomes following SVR. Preoperative assessment of RV volume and function using cardiac MRI may improve the risk stratification of SVR.
• A randomized phase II study evaluating pyridoxine for the prevention of hand-foot syndrome associated with capecitabine therapy for advanced or metastatic breast cancer.

  Tatsuya Toyama, Akiyo Yoshimura, Takako Hayashi, Naomi Kobayashi, Kanako Saito, Michiko Tsuneizumi, Masataka Sawaki, Masaya Hattori, Takumi Nakada, Isao Yokota, Hiroji Iwata

  Breast cancer (Tokyo, Japan) 25 6 729 - 735 2018年11月 [査読有り][通常論文]
   

  BACKGROUND: Pyridoxine, an activated form of vitamin B6 used to treat allergic dermatitis, may prevent capecitabine-associated hand-foot syndrome (HFS), although evidence of the benefit of prophylactic pyridoxine is lacking. The aim of this open-label, multicenter, randomized phase II study was to determine whether prophylactic pyridoxine could delay the onset of capecitabine-induced HFS in patients with advanced or metastatic breast cancer. METHODS: Patients received either concomitant pyridoxine (60 mg per day; pyridoxine group), or no pyridoxine but treatment with capecitabine-containing regimens (no pyridoxine group). Study treatment was administered until the development of grade 2 or worse HFS or disease progression. The primary endpoint was the time to onset of grade 2 or worse HFS from the start of protocol treatment. RESULTS: A total of 135 patients were randomized to the pyridoxine (n = 67) or no pyridoxine (n = 68) groups. Grade 2 or worse HFS developed in 19 of 66 patients (28.8%) versus 21 of 67 patients (31.3%) in the pyridoxine and no pyridoxine groups, respectively. The median time to onset of grade 2 or worse HFS was 13.6 and 10.6 months in the pyridoxine and no pyridoxine groups, respectively [hazard ratio = 0.75 (80% confidence interval 0.50-1.13), one-sided P = 0.18]. CONCLUSIONS: Prophylactic pyridoxine was not shown to have an effect on the onset of capecitabine-associated HFS in this study.
• Involvement of anterior and posterior corneal surface area imbalance in the pathological change of keratoconus.

  Koji Kitazawa, Motohiro Itoi, Isao Yokota, Koichi Wakimasu, Yuko Cho, Yo Nakamura, Osamu Hieda, Shigeru Kinoshita, Chie Sotozono

  Scientific reports 8 1 14993 - 14993 2018年10月09日 [査読有り][通常論文]
   

  Keratoconus (KC) is an ectatic disorder with a high prevalence rate. However, the exact cause of the disease and possible underlying mechanisms of development remain unclear. In this present study, we aimed to investigate the anterior and the posterior corneal surface area in normal, forme fruste keratoconus (FFKC), and keratoconic eyes (as a reference group) using anterior segment optical coherence tomography (AS-OCT) in order to assess the pathological change of KC. The surface areas of the anterior or posterior cornea, and the anterior-posterior (As/Ps) ratio of corneal surface area, were measured at the central 5.0 mm-, 6.0 mm-, and 7.0 mm-diameter areas via AS-OCT, and a comparison between the normal eyes and FFKC eyes was then performed using the Mann-Whitney U test. The posterior surface area at the central 5.0 mm areas in the FFKC eyes (20.430 mm2) and KC eyes (20.917 mm2) seemed to become larger than that of normal eyes (20.389 mm2) (normal vs FFKC; P = 0.06). Moreover, the As/Ps of the corneal surface area in the FFKC eyes (0.986) and the KC eyes (0.976) was significantly smaller than that of the normal eyes (0.988) (normal vs FFKC; P < 0.01). Anterior and posterior corneal surface area imbalance may reflect keratoconic eyes at the early stage of the disease.
• Moderately Long-Term Safety and Efficacy of Repeat Penetrating Keratoplasty.

  Koji Kitazawa, Koichi Wakimasu, Kanae Kayukawa, Isao Yokota, Tsutomu Inatomi, Osamu Hieda, Chie Sotozono, Shigeru Kinoshita

  Cornea 37 10 1255 - 1259 2018年10月 [査読有り][通常論文]
   

  PURPOSE: To investigate the moderately long-term safety and efficacy of repeat penetrating keratoplasty (PK) for treatment of a failed PK graft. METHODS: Retrospective consecutive clinical case series. Of 992 consecutive cases that underwent PK at Baptist Eye Institute, Kyoto, Japan, between April 1998 and September 2013, 96 cases that underwent repeat PK with more than 3 years postoperatively follow-up were retrospectively reviewed. Surgical outcomes including donor graft survival rate, best spectacle-corrected visual acuity, endothelial cell density, and complications afeter repeat PK were assessed. RESULTS: At 1, 3, and 5 years after repeat PK, the donor graft survival rate was 91%, 75%, and 64%, respectively, and the mean endothelial cell density in those survived grafts was 1778, 1207, and 989 cells/mm, respectively. Best spectacle-corrected visual acuity over 20/200 and 20/40 was achieved in 71% and 27% of the patients, respectively, at 1 year postoperatively, in 59% and 31% of the patients, respectively, at 3 years postoperatively, and in 53% and 29% of the patients, respectively, at 5 years postoperatively. The most common complication for repeat PK was the need for additional glaucoma surgery [n = 11 patients (11.5%)]. Cox proportional hazard regression analyses revealed that previous glaucoma surgery and a rejection episode were high risk factors for graft failure in repeat PK [hazard ratio (HR) = 6.7; 95% confidence interval (CI), 2.1-21.2 and HR = 5.6; 95% CI, 1.8-18.0, respectively]. CONCLUSIONS: Repeat PK provided relatively safe and effective moderately long-term surgical outcomes.
• Number of Nodules but not Size of Hepatocellular Carcinoma Can Predict Refractoriness to Transarterial Chemoembolization and Poor Prognosis

  Kazuhiro Katayama, Toshihiro Imai, Yutaro Abe, Tadatoshi Nawa, Noboru Maeda, Katsuyuki Nakanishi, Hiroshi Wada, Keisuke Fukui, Yuri Ito, Isao Yokota, Kazuyoshi Ohkawa

  Journal of Clinical Medicine Research 10 10 765 - 771 2018年10月 [査読有り][通常論文]
  
• Mevalonate pathway blockage enhances the efficacy of mTOR inhibitors with the activation of retinoblastoma protein in renal cell carcinoma

  Nobuhisa Hagiwara, Motoki Watanabe, Mahiro Iizuka-Ohashi, Isao Yokota, Seijiro Toriyama, Mamiko Sukeno, Mitsuhiro Tomosugi, Yoshihiro Sowa, Fumiya Hongo, Kazuya Mikami, Jintetsu Soh, Akira Fujito, Hiroaki Miyashita, Yukako Morioka, Tsuneharu Miki, Osamu Ukimura, Toshiyuki Sakai

  Cancer Letters 431 182 - 189 2018年09月01日 [査読有り][通常論文]
   

  Renal cell carcinoma (RCC) is the most common malignancy of kidney and remains largely intractable once it recurs after resection. mTOR inhibitors have been one of the mainstays used against recurrent RCC however, there has been a major problem of the resistance to mTOR inhibitors, and thus new combination treatments with mTOR inhibitors are required. We here retrospectively showed that regular use of antilipidemic drug statins could provide a longer progression free survival (PFS) in RCC patients prescribed with an mTOR inhibitor everolimus than without statins (median PFS, 7.5 months vs. 3.2 months, respectively hazard ratio, 0.52 95% CI, 0.22–1.11). In order to give a rationale for this finding, we used RCC cell lines and showed the combinatorial effects of an mTOR inhibitor with statins induced a robust activation of retinoblastoma protein, whose mechanisms were involved in statins-mediated hindrance of KRAS or Rac1 protein prenylation. Finally, statins treatment also enhanced the efficacy of an mTOR inhibitor in RCC xenograft models. Thus, we provide molecular and (pre)clinical data showing that statins use could be a drug repositioning for RCC patients to enhance the efficacy of mTOR inhibitors.
• Diagnostic performance of initial enhancement analysis using ultra-fast dynamic contrast-enhanced MRI for breast lesions.

  Goto M, Sakai K, Yokota H, Kiba M, Yoshida M, Imai H, Weiland E, Yokota I, Yamada K

  European radiology 29 3 1164 - 1174 2018年08月 [査読有り][通常論文]
   

  Objectives: To assess the diagnostic value and contribution to BI-RADS categorisation of initial enhancement on ultra-fast DCE-MRI for differentiating malignant and benign breast lesions. Methods: The institutional review board approved this study, and written informed consent was obtained from each participant. Both ultra-fast DCE-MRI for initial enhancement analysis and conventional MRI were performed on 200 subjects with a total of 215 lesions (147 malignant and 68 benign). BI-RADS categorisation of enhancing lesions was performed using the conventional MRI. Two initial enhancement measures, time to enhancement (TTE) and maximum slope (MS), were derived from the ultra-fast DCE-MRI. Diagnostic performance and the additional diagnostic value of adding TTE and MS to BI-RADS were evaluated. Results: Both TTE and MS showed significant differences between malignant and benign breast lesions in masses (TTE, p <.001; MS, p =.006) and non-mass enhancement (NME) (TTE, p <.001; MS, p <.001). For masses, the AUC of TTE+MS combined with BI-RADS (0.864) was better than BI-RADS alone (0.823, p =.065). For NME, the AUC of TTE+MS combined with BI-RADS (0.923) was significantly larger than BI-RADS alone (0.865, p =.036), and diagnostic specificity improved by 40.9% (p =.005), without a significant decrease in the sensitivity (p =.083). Conclusion: Initial enhancement analysis using ultra-fast DCE-MRI is especially useful for increasing the diagnostic performance of NME in breast MRI. Key Points: • Ultra-fast dynamic MRI effectively differentiates benign from malignant breast lesions. • Ultra-fast dynamic MRI contributes to BI-RADS categorisation in non-mass enhancement. • Management of non-mass breast lesions becomes more appropriate.
• The detection of white matter alterations in obsessive–compulsive disorder revealed by TRActs Constrained by UnderLying Anatomy (TRACULA)

  Anri Watanabe, Takashi Nakamae, Yuki Sakai, Seiji Nishida, Yoshinari Abe, Kei Yamada, Isao Yokota, Jin Narumoto

  Neuropsychiatric Disease and Treatment 14 1635 - 1643 2018年06月 [査読有り][通常論文]
  
• Prognostic significance of day-by-day variability of home blood pressure on progression to macroalbuminuria in patients with diabetes

  Emi Ushigome, Shinobu Matsumoto, Chikako Oyabu, Noriyuki Kitagawa, Toru Tanaka, Goji Hasegawa, Masayoshi Ohnishi, Sei Tsunoda, Hidetaka Ushigome, Isao Yokota, Naoto Nakamura, Yohei Oda, Mai Asano, Muhei Tanaka, Masahiro Yamazaki, Michiaki Fukui

  Journal of Hypertension 36 5 1068 - 1075 2018年05月01日 [査読有り][通常論文]
   

  Objectives: Previously, we have shown in cross-sectional analysis of patients with type 2 diabetes mellitus that the presence of diabetic nephropathy is associated with increased home blood pressure (HBP) variability. We now examine the prognostic significance of HBP variability in substantially the same cohort. Methods: We performed a prospective cohort study of type 2 diabetes patients. We analyzed 714 patients. Major exclusion criteria are missing data of urinary albumin excretion and newly prescribed or stopped renin-angiotensin system inhibitors during 2-year follow-up. Patients were instructed to perform triplicate morning and evening HBP measurements for 14 consecutive days. We computed day-by-day HBP variability as within-patient standard deviation (SD) and coefficient of variation (CV) of measurements. Results: During the follow-up period of 2 years, 23 patients progressed to macroalbuminuria. The changing risk of progression to macroalbuminuria with increasing day-by-day variability of morning SBP was better depicted using smoothing spline analyses. Patients with greater SD of morning SBP tended to significantly progress to macroalbuminuria [odds ratio: 5.24 (95% confidence interval: 2.10-13.03 P > 0.001)]. Patients with greater CV of morning SBP also tended to significantly progress to macroalbuminuria [odds ratio: 3.36 (95% confidence interval: 1.39-8.12 P = 0.007)]. Conclusion: Day-by-day variability of morning SBP was proven as an independent predictor for progression to macroalbuminuria in patients with type 2 diabetes.
• Pomalidomide with or without dexamethasone for relapsed/refractory multiple myeloma in Japan: a retrospective analysis by the Kansai Myeloma Forum.

  Yayoi Matsumura-Kimoto, Junya Kuroda, Hitomi Kaneko, Yuri Kamitsuji, Shin-Ichi Fuchida, Aya Nakaya, Hirohiko Shibayama, Nobuhiko Uoshima, Isao Yokota, Hitoji Uchiyama, Hideo Yagi, Satoru Kosugi, Toshimitsu Matsui, Jun Ishikawa, Mitsuhiro Matsuda, Kensuke Ohta, Masato Iida, Hirokazu Tanaka, Masayuki Kobayashi, Katsuya Wada, Chihiro Shimazaki, Shosaku Nomura, Kazunori Imada, Masayuki Hino, Itaru Matsumura, Yuzuru Kanakura, Akifumi Takaori-Kondo

  International journal of hematology 107 5 541 - 550 2018年05月 [査読有り][通常論文]
   

  Determinants of the efficacy and safety of pomalidomide (POM) monotherapy or POM plus dexamethasone (DEX) (POM/DEX) for relapsed and refractory multiple myeloma (RRMM) were examined retrospectively in a real-world clinical practice setting in Japan. The subjects were 108 patients registered with the Kansai Myeloma Forum, who were treated with either POM or POM/DEX. Of these, 79 (73%), 73 (68%), and 58 (54%) were resistant to bortezomib (BTZ), lenalidomide (LEN), and both BTZ and LEN, respectively. The median overall survival (OS) was not reached. The median time to treatment failure (TTF) was 4.4 months. The best response was recorded in 96 patients, with a 31% overall response rate (ORR) and a 79% rate of achieving at least stable disease. Number of pre-POM regimens ≥ 5, non-IgG-type M-protein, and time from initial therapy to POM or POM/DEX therapy < 2 years were associated with shorter TTF and OS. Frequent (> 10%) severe adverse events included neutropenia (55.1%), thrombocytopenia (33.7%), anemia (30.6%), febrile neutropenia (12.2%), fatigue (11.2%), and anorexia (10.2%). In conclusion, POM and POM/DEX showed substantial efficacy against RRMM, but new combination therapies with POM are needed to improve efficacy further without causing hematologic toxicities.
• Prognostic significance of home pulse pressure for progression of diabetic nephropathy: KAMOGAWA-HBP study article

  Noriyuki Kitagawa, Emi Ushigome, Shinobu Matsumoto, Chikako Oyabu, Hidetaka Ushigome, Isao Yokota, Mai Asano, Muhei Tanaka, Masahiro Yamazaki, Michiaki Fukui

  Hypertension Research 41 5 363 - 371 2018年05月01日 [査読有り][通常論文]
   

  Pulse pressure (PP) has been noted as a potential independent risk factor for micro and macrovascular diabetic complications. We aimed to examine the prognostic value of home-measured PP (home PP) in patients with type 2 diabetes. This study is a 2-year prospective cohort study of 737 patients with type 2 diabetes. Home blood pressure measurements were performed for 14 consecutive days. We defined the progression of diabetic nephropathy as when the diabetic nephropathy stage advanced to a higher stage during the 2 years. Using logistic regression analyses, we investigated the relationship between home PP and home systolic blood pressure (SBP) in the morning and in the evening and the progression of diabetic nephropathy. Furthermore, we measured the area under the receiver-operating characteristic curve (AUC) to assess the predictive ability of the progression of diabetic nephropathy of home PP. During the 2-year study, progression of diabetic nephropathy was observed in 94 patients. The adjusted odds ratios (95% confidence interval (CI)) of home PP and home SBP to the progression of diabetic nephropathy were 1.23 (1.01-1.49) and 1.14 (0.98-1.33), respectively. The AUC (95% CI) of home PP to the progression of diabetic nephropathy was 0.624 (0.665-0.679). The optimal cut-off points, sensitivity and specificity for home PP that were associated with the progression of diabetic nephropathy were 57.7 mmHg, 0.649 and 0.580, respectively. Our findings suggest, for the first time, that home PP is an independent predictor of the progression of diabetic nephropathy in patients with type 2 diabetes.
• Impact of masked hypertension on diabetic nephropathy in patients with type II diabetes: a KAMOGAWA-HBP study.

  Ushigome E, Oyabu C, Tanaka T, Hasegawa G, Ohnishi M, Tsunoda S, Ushigome H, Yokota I, Nakamura N, Oda Y, Asano M, Tanaka M, Yamazaki M, Fukui M

  Journal of the American Society of Hypertension : JASH 12 5 364 - 371.e1 2018年05月01日 [査読有り][通常論文]
   

  The prognostic significance of masked hypertension (MH) on the progression of diabetic nephropathy among patients with type II diabetes is not well documented. We examined the relationship between clinic systolic blood pressure (SBP) and morning home SBP measurements and progression to macroalbuminuria in patients with type II diabetes. We analyzed prospective cohort study data from 712 patients with type II diabetes. We classified the patients into the following four groups according to their clinic (130 mm Hg) and home (125 mm Hg) SBP measurements: controlled blood pressure group, white-coat hypertension group, MH group, and sustained hypertension (SH) group. The patients were instructed to perform triplicate morning and evening blood pressure measurements for 14 consecutive days. During the 2-year follow-up period, 23 patients progressed to macroalbuminuria. The unadjusted odds ratio (95% confidence interval) for progression to macroalbuminuria among the patients with MH was significantly higher than that among the patients with controlled blood pressure (8.89 [1.06–74.88]). No significant relationship was observed between white-coat hypertension or SH and progression to macroalbuminuria. In analyses adjusted for various potential confounders, the adjusted odds ratio for progression to macroalbuminuria in the MH group was more than 8-fold higher than that in the controlled blood pressure group. MH might be a predictor of progression to macroalbuminuria among patients with type II diabetes. This rate of progression is comparable with or greater than the results reported for patients with SH.
• Injection of Cultured Cells with a ROCK Inhibitor for Bullous Keratopathy.

  Shigeru Kinoshita, Noriko Koizumi, Morio Ueno, Naoki Okumura, Kojiro Imai, Hiroshi Tanaka, Yuji Yamamoto, Takahiro Nakamura, Tsutomu Inatomi, John Bush, Munetoyo Toda, Michio Hagiya, Isao Yokota, Satoshi Teramukai, Chie Sotozono, Junji Hamuro

  The New England journal of medicine 378 11 995 - 1003 2018年03月15日 [査読有り][通常論文]
   

  BACKGROUND: Corneal endothelial cell (CEC) disorders, such as Fuchs's endothelial corneal dystrophy, induce abnormal corneal hydration and result in corneal haziness and vision loss known as bullous keratopathy. We investigated whether injection of cultured human CECs supplemented with a rho-associated protein kinase (ROCK) inhibitor into the anterior chamber could increase CEC density. METHODS: We performed an uncontrolled, single-group study involving 11 persons who had received a diagnosis of bullous keratopathy and had no detectable CECs. Human CECs were cultured from a donor cornea; a total of 1×106 passaged cells were supplemented with a ROCK inhibitor (final volume, 300 μl) and injected into the anterior chamber of the eye that was selected for treatment. After the procedure, patients were placed in a prone position for 3 hours. The primary outcome was restoration of corneal transparency, with a CEC density of more than 500 cells per square millimeter at the central cornea at 24 weeks after cell injection. Secondary outcomes were a corneal thickness of less than 630 μm and an improvement in best corrected visual acuity equivalent to two lines or more on a Landolt C eye chart at 24 weeks after cell injection. RESULTS: At 24 weeks after cell injection, we recorded a CEC density of more than 500 cells per square millimeter (range, 947 to 2833) in 11 of the 11 treated eyes (100%; 95% confidence interval [CI], 72 to 100), of which 10 had a CEC density exceeding 1000 cells per square millimeter. A corneal thickness of less than 630 μm (range, 489 to 640) was attained in 10 of the 11 treated eyes (91%; 95% CI, 59 to 100), and an improvement in best corrected visual acuity of two lines or more was recorded in 9 of the 11 treated eyes (82%; 95% CI, 48 to 98). CONCLUSIONS: Injection of human CECs supplemented with a ROCK inhibitor was followed by an increase in CEC density after 24 weeks in 11 persons with bullous keratopathy. (Funded by the Japan Agency for Medical Research and Development and others; UMIN number, UMIN000012534 .).
• Threshold value of home pulse pressure predicting arterial stiffness in patients with type 2 diabetes: KAMOGAWA-HBP study

  Noriyuki Kitagawa, Emi Ushigome, Shinobu Matsumoto, Chikako Oyabu, Hidetaka Ushigome, Isao Yokota, Mai Asano, Muhei Tanaka, Masahiro Yamazaki, Michiaki Fukui

  Journal of Clinical Hypertension 20 3 472 - 477 2018年03月01日 [査読有り][通常論文]
   

  This cross-sectional multicenter study was designed to evaluate the threshold value of home pulse pressure (PP) and home systolic blood pressure (SBP) predicting the arterial stiffness in 876 patients with type 2 diabetes. We measured the area under the receiver-operating characteristic curve (AUC) and estimated the ability of home PP to identify arterial stiffness using Youden-Index defined cut-off point. The arterial stiffness was measured using the brachial-ankle pulse wave velocity (baPWV). AUC for arterial stiffness in morning PP was significantly greater than that in morning SBP (P < .001). AUC for arterial stiffness in evening PP was also significantly greater than that in evening SBP (P < .001). The optimal cut-off points for morning PP and evening PP, which predicted arterial stiffness, were 54.6 and 56.9 mm Hg, respectively. Our findings indicate that we should pay more attention to increased home PP in patients with type 2 diabetes.
• Chromosomal abnormality variation detected by G-banding is associated with prognosis of diffuse large B-cell lymphoma treated by R-CHOP-based therapy.

  Yoshimi Mizuno, Taku Tsukamoto, Eri Kawata, Nobuhiko Uoshima, Hitoji Uchiyama, Isao Yokota, Saori Maegawa, Tomoko Takimoto, Kazuna Tanba, Yayoi Matsumura-Kimoto, Saeko Kuwahara-Ota, Yuto Fujibayashi, Mio Yamamoto-Sugitani, Yoshiaki Chinen, Yuji Shimura, Shigeo Horiike, Masafumi Taniwaki, Tsutomu Kobayashi, Junya Kuroda

  Cancer medicine 7 3 655 - 664 2018年03月 [査読有り][通常論文]
   

  Diffuse large B-cell lymphoma (DLBCL), which is the most prevalent disease subtype of non-Hodgkin lymphoma, is highly heterogeneous in terms of cytogenetic and molecular features. This study retrospectively investigated the clinical impact of G-banding-defined chromosomal abnormality on treatment outcomes of DLBCL in the era of rituximab-containing immunochemotherapy. Of 181 patients who were diagnosed with DLBCL and treated with R-CHOP or an R-CHOP-like regimen between January 2006 and April 2014, metaphase spreads were evaluable for G-banding in 120. In these 120 patients, 40 were found to harbor a single chromosomal aberration type; 63 showed chromosomal abnormality variations (CAVs), which are defined by the presence of different types of chromosomal abnormalities in G-banding, including 19 with two CAVs and 44 with ≥3 CAVs; and 17 had normal karyotypes. No specific chromosomal break point or numerical abnormality was associated with overall survival (OS) or progression-free survival (PFS), but the presence of ≥3 CAVs was significantly associated with inferior OS rates (hazard ratio (HR): 2.222, 95% confidence interval (CI): 1.056-4.677, P = 0.031) and tended to be associated with shorter PFS (HR: 1.796, 95% CI: 0.965-3.344, P = 0.061). In addition, ≥3 CAVs more frequently accumulated in high-risk patients, as defined by several conventional prognostic indices, such as the revised International Prognostic Index. In conclusion, our results suggest that the emergence of more CAVs, especially ≥3, based on chromosomal instability underlies the development of high-risk disease features and a poor prognosis in DLBCL.
• Examination time as a quality indicator of screening upper gastrointestinal endoscopy for asymptomatic examinees

  Takuji Kawamura, Hironori Wada, Naokuni Sakiyama, Yuki Ueda, Atsushi Shirakawa, Yusuke Okada, Kasumi Sanada, Kojiro Nakase, Koichiro Mandai, Azumi Suzuki, Mai Kamaguchi, Atsuhiro Morita, Kenichi Nishioji, Kiyohito Tanaka, Naomi Mochizuki, Koji Uno, Isao Yokota, Masao Kobayashi, Kenjiro Yasuda

  Gastroenterological Endoscopy 60 2 180 - 188 2018年02月01日 [査読有り][通常論文]
   

  Background and Aim : The significance of examination time of esophagogastroduodenoscopy (EGD) for asymptomatic examinees is yet to be established. We aimed to clarify whether endoscopists who allot more examination time can detect higher numbers of neoplastic lesions among asymptomatic examinees. Methods : We reviewed a database of consecutive examinees who underwent EGD in our hospital from April 2010 to September 2015. Staff endoscopists were classified into fast, moderate, and slow groups based on the mean examination time of EGD without a biopsy. Neoplastic lesion detection rate among these groups was compared using multiple logistic regression. Results : Of the 55 786 consecutive examinees who underwent EGD, 15 763 asymptomatic examinees who were screened by staff doctors were analyzed. Mean examination time of 13 661 EGD without biopsy was 6.2 min (range, 2-18 min). When cut-off times of 5 and 7 min were used, four endoscopists were classified into the fast (mean duration, 4.4±1.0 min), 12 into the moderate (6.1± 1.4 min), and four into the slow (7.8±1.9 min) groups. Neoplastic lesion detection rates in the fast, moderate, and slow groups were 0.57% (13/2288), 0.97% (99/10,180), and 0.94% (31/3295), respectively. Compared with that in the fast group, odds ratios for the neoplastic lesion detection rate in the moderate and slow groups were 1.90 (95% confidence interval [CI], 1.06-3.40) and 1.89 (95% CI, 0.98-3.64), respectively. Conclusion : Endoscopists who do not allot adequate examination time may overlook neoplastic lesions in the upper gastrointestinal tract.
• Reply to "Relative Survival Instead of Overall Survival Should be Used as Outcome When Analyzing the Effect of Age After Treatment of Hepatocellular Carcinoma"

  Kaibori, M., Yoshii, K., Yokota, I.

  Annals of surgery 268 6 e76 - e77 2018年02月 [査読有り][通常論文]
  
• Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07: a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG)

  Hishiki, T., Matsumoto, K., Ohira, M., Kamijo, T., Shichino, H., Kuroda, T., Yoneda, A., Soejima, T., Nakazawa, A., Takimoto, T., Yokota, I., Teramukai, S., Takahashi, H., Fukushima, T., Kaneko, T., Hara, J., Kaneko, M., Ikeda, H., Tajiri, T., Nakagawara, A.

  International Journal of Clinical Oncology 23 5 2018年
• Results of a phase II trial for high-risk neuroblastoma treatment protocol JN-H-07: a report from the Japan Childhood Cancer Group Neuroblastoma Committee (JNBSG)

  Hishiki, T., Matsumoto, K., Ohira, M., Kamijo, T., Shichino, H., Kuroda, T., Yoneda, A., Soejima, T., Nakazawa, A., Takimoto, T., Yokota, I., Teramukai, S., Takahashi, H., Fukushima, T., Kaneko, T., Hara, J., Kaneko, M., Ikeda, H., Tajiri, T., Nakagawara, A.

  International Journal of Clinical Oncology 23 5 2018年
• Significant Role of Eukaryotic Initiation Factor 4E as a Predictor for Distant Metastasis in Completely Resected Pathological Stage I -HA Lung Adenocarcinoma

  Sakamoto, T., Sawada, S., Yokota, I., Seki, R., Ota, S., Seki, N.

  Teikyo Medical Journal 41 1 2018年
• Association of fatty pancreas with pancreatic endocrine and exocrine function.

  Hayato Miyake, Junichi Sakagami, Hiroaki Yasuda, Yoshio Sogame, Ryusuke Kato, Kanetoshi Suwa, Katsuyuki Dainaka, Tomoki Takata, Isao Yokota, Yoshito Itoh

  PloS one 13 12 e0209448  2018年 [査読有り][通常論文]
   

  AIM: The purpose of this study was to clarify whether fatty pancreas might lead to impaired pancreatic endocrine or exocrine function. MATERIAL AND METHODS: The study involved 109 participants who had undergone the glucagon stimulation test and N-benzoyl-L-tyros-p-amino benzoic acid (BT-PABA) test to assess pancreatic function as well as unenhanced abdominal computed tomography (CT). Pancreatic endocrine impairment was defined as ΔC peptide immunoreactivity less than 2 [mmol/L] in the glucagon stimulation test, and pancreatic exocrine impairment was defined as a urinary PABA excretion rate less than 70% on the BT-PABA test. We defined as the mean CT value of pancreas / CT value of spleen (P/S ratio) as a marker to assess fatty pancreas. We analyzed the association between fatty pancreas and pancreatic impairment using the logistic regression model. The odds ratio (OR) is shown per 0.1 unit. RESULTS: Pancreatic endocrine function was impaired in 33.0% of the participants, and 56.9% of those were regarded as having pancreatic exocrine impairment. The P/S ratio was significantly correlated with pancreatic endocrine impairment in univariate analysis (OR = 0.61, 95% confidence interval (CI) = 0.43-0.83, P = 0.0013) and multivariate analysis (OR = 0.38, 95% CI = 0.22-0.61, P < .0001) for all participants. Similar significant relationships were observed in both univariate (OR = 0.70, 95% CI = 0.49-0.99, P = 0.04) and multivariate (OR = 0.39, 95% CI = 0.21-0.66, P = 0.0002) analyses for the participants without diabetes (n = 93). The amount of pancreatic fat was not associated with exocrine impairment in univariate analysis (OR = 0.80, 95% CI = 0.59-1.06, P = 0.12). CONCLUSION: Fatty pancreas was associated with pancreatic endocrine impairment but did not have a clear relationship with pancreatic exocrine impairment.
• Classification of acute pain trajectory after breast cancer surgery identifies patients at risk for persistent pain: a prospective observational study.

  Akiko Okamoto, Masaki Yamasaki, Isao Yokota, Maiko Mori, Megumi Matsuda, Yosuke Yamaguchi, Shunsuke Yamakita, Hiroshi Ueno, Teiji Sawa, Tetsuya Taguchi, Toyoshi Hosokawa, Fumimasa Amaya

  Journal of pain research 11 2197 - 2206 2018年 [査読有り][通常論文]
   

  Purpose: Predictive value and accuracy of the acute pain trajectory were compared with those of pain intensity at 1 day after the surgery for pain prevalence at 6 months after the surgery. Materials and methods: Female patients scheduled for breast cancer surgery were eligible for this study. Patients were questioned about pain intensity daily during the 7 days after surgery. Presence of pain, its location, and intensity as well as the Japanese version of the quality of the recovery-40 (QOR-40) were determined in an interview prior to and at 6 months after the surgery. Acute pain trajectory was determined by a group-based trajectory modeling analysis that was based on the pain intensity at 1-7 days after surgery. Predictive value of the acute pain trajectory for the presence of pain at 6 months after the surgery was assessed by a logistic regression model. The predictive value was compared with pain intensity at 1 day after the surgery. Results: A total of 123 participants completed the 6-month follow-up. The three-cluster model (mild, moderate, and severe pain) was considered to be the most statistically appropriate model for the acute pain trajectory. After 6 months, 51.2% and 8.9% of participants reported pain and severe pain, respectively. Presence of pain at 6 months after the surgery was associated with poor recovery. The severe pain cluster was significantly associated with the presence of pain at 6 months after the surgery (adjusted odds ratio, 9.40; P<0.001 vs mild pain cluster). Conclusion: Classification of patients according to the acute pain trajectory, when compared with the classification according to pain intensity at 1 day after the surgery, made it possible to predict with better precision those patients who will develop persistent postsurgical pain.
• Automated renal cortical volume measurement for assessment of renal function in patients undergoing radical nephrectomy

  Hirofumi Shimoyama, Shuji Isotani, Toshiyuki China, Masayoshi Nagata, Isao Yokota, Kosuke Kitamura, Yoshiaki Wakumoto, Hisamitsu Ide, Satoru Muto, Akira Tujimura, Raizo Yamaguchi, Shigeo Horie

  CLINICAL AND EXPERIMENTAL NEPHROLOGY 21 6 1124 - 1130 2017年12月 [査読有り][通常論文]
   

  Renal volume change greatly affects renal function after nephrectomy. Although various measuring techniques were reported, no standard measuring method is available. In this study, we examined the computational automated volumetric method, and evaluated the volumetric change to assess the functional outcome in patients undergoing radical nephrectomy. We developed the predictive equation for postoperative renal function from volume alternation and validated the performance. Thirty-two patients undergoing radical nephrectomy participated in this study. Renal volume was calculated using three different methods [ellipsoid method, conventional manual voxel count method for renal parenchyma (manual RPV), and automated voxel count method for renal cortex (automated RCV)] through newly developed imaging software. Statistical analysis was performed to evaluate the correlation between renal functional alternation 7 days after the nephrectomy and renal volumetric change. A simple predictive equation for the postoperative renal function by renal volume loss was developed and externally validated through another 12 cases. The automated RCV method had the strongest correlation between renal function alternation and RCV change (R = 0.82), than manual RPV (R = 0.69) and ellipsoid method (R = 0.50). Subsequently, a simple equation for postoperative renal function by renal volume alternation was developed: predicted postoperative estimated glomerular filtration rate (eGFR) from renal volume change = preoperative eGFR x (postoperative renal volume / preoperative renal volume). In the external validation cohort, automated RCV demonstrated the predictive performance of the constructed equations for renal function (R = 0.77). The computational automated RCV measurements is a simple estimation of renal functional outcome for patients undergoing radical nephrectomy.
• Reply.

  Koji Kitazawa, Kanae Kayukawa, Koichi Wakimasu, Isao Yokota, Tsutomu Inatomi, Osamu Hieda, Kazuhiko Mori, Chie Sotozono, Shigeru Kinoshita

  Ophthalmology 124 12 e86-e87 - e87 2017年12月 [査読有り][通常論文]
  
• Fixed-flexion view X-ray of the knee superior in detection and follow-up of knee osteoarthritis

  Hiroyuki Kan, Yuji Arai, Masashi Kobayashi, Shuji Nakagawa, Hiroaki Inoue, Manabu Hino, Shintaro Komaki, Kazuya Ikoma, Keiichiro Ueshima, Hiroyoshi Fujiwara, Isao Yokota, Toshikazu Kubo

  Medicine (United States) 96 49 e9126  2017年12月01日 [査読有り][通常論文]
   

  A fixed flexion view (FFV) is useful for evaluating joint space when assessing the severity of osteoarthritis (OA) of the knee. We analyzed changes in joint space revealed by standing extended view (SEV) and FFV over a mean 4 years, to compare both views on their capacity to measure joint space width accurately at particular time points during follow-up. SEV and FFV images were acquired in patients with knee OA. The 81 patients (157 knees) followed up for ≥24 months were selected as study subjects. Medial joint space widths (MJSW), Kellgren-Lawrence (KL) grades, and reductions in MJSW on SEV (ΔSEV) and FFV (ΔFFV) were compared in knees evaluated by SEV and FFV. At both time-points, mean MJSW was significantly lower by FFV than by SEV. Mean MJSW was significantly lower at follow-up than at first examination by both SEV and FFV. At both time-points, the KL grade was higher by FFV than by SEV group. The ΔFFV was significantly greater than the ΔSEV. ΔSEV did not differ significantly among KL grades, but ΔFFV was significantly greater in patients with KL grade II than in patients with other KL grades. FFV is not only useful for evaluating joint space in knees with OA, but also for accurately evaluating the progression of OA. The risk of rapid progression of knee OA may be higher in patients with KL grade II, as determined by FFV. FFV may be superior to SEV in determining appropriate treatment strategies for knee OA.
• Mini-Mental State Examination score trajectories and incident disabling dementia among community-dwelling older Japanese adults

  Yu Taniguchi, Akihiko Kitamura, Hiroshi Murayama, Hidenori Amano, Tomohiro Shinozaki, Isao Yokota, Satoshi Seino, Yu Nofuji, Mariko Nishi, Yuri Yokoyama, Yutaka Matsuyama, Yoshinori Fujiwara, Shoji Shinkai

  GERIATRICS & GERONTOLOGY INTERNATIONAL 17 11 1928 - 1935 2017年11月 [査読有り][通常論文]
   

  AimThe present prospective study used repeated measures analysis to identify potential Mini-Mental State Examination (MMSE) score trajectories and determine whether MMSE trajectory was associated with incident disabling dementia among community-dwelling older Japanese adults. MethodsA total of 1724 non-demented adults (mean age 71.4 years [SD 5.7]; 56.7% women) aged 65-90 years participated in annual geriatric health assessments during the period from June 2002 through July 2014. The total number of observations was 6755, and the average number of follow-up assessments was 3.9. A review of municipal databases in the Japanese public long-term care insurance system showed that 205 (11.9%) participants developed disabling dementia through December 2014. ResultsWe identified three distinct MMSE score trajectory patterns (high, middle and low) in adults aged 65-90 years. After adjusting for important confounders, participants with middle (42.8%) and low (5.1%) MMSE trajectories had hazard ratios of 2.46 (95% confidence interval 1.64-3.68) and 10.73 (95% confidence interval 4.91-23.45), respectively, for incident disabling dementia, as compared with those in the high (52.1%) trajectory group. ConclusionsApproximately half of the participants were classified as having a high MMSE trajectory, whereas 43% and 5% had middle and low MMSE trajectories, respectively, in this population. Individuals with middle and low MMSE trajectories had a higher risk for incident disabling dementia, which suggests that a high-risk approach to dementia prevention should target people with mild and more rapid cognitive decline. Geriatr Gerontol Int 2017; 17: 1928-1935.
• Maximum home blood pressure is a useful indicator of diabetic nephropathy in patients with type 2 diabetes mellitus: KAMOGAWA-HBP study

  Chikako Oyabu, Emi Ushigome, Shinobu Matsumoto, Toru Tanaka, Goji Hasegawa, Naoto Nakamura, Masayoshi Ohnishi, Sei Tsunoda, Hidetaka Ushigome, Isao Yokota, Muhei Tanaka, Mai Asano, Masahiro Yamazaki, Michiaki Fukui

  DIABETES & VASCULAR DISEASE RESEARCH 14 6 477 - 484 2017年11月 [査読有り][通常論文]
   

  Objective: Maximum home systolic blood pressure has been shown to predict target organ damage. We aimed to clarify the association between maximum home systolic blood pressure and urine albumin to creatinine ratio, an indicator of early-phase diabetic nephropathy in patients with type 2 diabetes. Methods: In 1040 patients, we assessed the relationship of mean or maximum home systolic blood pressure and urine albumin to creatinine ratio, and compared the area under the receiver operating characteristic curve of mean or maximum home systolic blood pressure for diabetic nephropathy (urine albumin to creatinine ratio 30mg/g Cr). Results: Multivariate linear regression analyses indicated that mean morning systolic blood pressure (=0.010, p<0.001) and maximum morning systolic blood pressure (=0.008, p<0.001) were significantly associated with urine albumin to creatinine ratio. Area under the receiver operating characteristic curve (95% confidence interval) for diabetic nephropathy in mean and maximum morning systolic blood pressure was 0.667 (0.634-0.700; p<0.001) and 0.671 (0.638-0.703; p<0.001), respectively. Conclusion: Maximum home systolic blood pressure, as well as mean home systolic blood pressure, was significantly associated with diabetic nephropathy in patients with type 2 diabetes.
• Impact of Advanced Age on Survival in Patients Undergoing Resection of Hepatocellular Carcinoma: Report of a Japanese Nationwide Survey.

  Kaibori M, Yoshii K, Yokota I, Hasegawa K, Nagashima F, Kubo S, Kon M, Izumi N, Kadoya M, Kudo M, Kumada T, Sakamoto M, Nakashima O, Matsuyama Y, Takayama T, Kokudo N, Liver Cancer Study, Group of Japan

  Annals of surgery 2017年09月 [査読有り][通常論文]
  
• Predictive clinical factors of cystoid macular edema in patients with Descemet's stripping automated endothelial keratoplasty.

  Koji Kitazawa, Kanae Kayukawa, Koichi Wakimasu, Isao Yokota, Tsutomu Inatomi, Osamu Hieda, Kazuhiko Mori, Chie Sotozono, Shigeru Kinoshita

  Scientific reports 7 1 7412 - 7412 2017年08月07日 [査読有り][通常論文]
   

  The purpose of this present study was to investigate predictive clinical factors associated with cystoid macular edema (CME) post Descemet's stripping automated endothelial keratoplasty (DSAEK) in a large case series. Of 393 consecutive patients who underwent DSAEK at Baptist Eye Institute, Kyoto, Japan between July 2011 and November 2016, 241 patients without CME at the pre- or early-postoperative periods were enrolled. The occurrence of anatomic CME was prospectively examined via optical coherence tomography (OCT). Possible predictive clinical factors for CME were analyzed by multivariate logistic regression analysis. At 1-month post DSAEK, CME occurred in 27 (11.2%) of the 241 patients. Multivariate analysis revealed that primary angle closure glaucoma (PACG) was significantly associated with postoperative CME (odds ratio = 6.4, P = 0.04). The findings of this study revealed that DSAEK in patients with PACG showed a high incidence of CME, thus indicating that they should undergo a careful postoperative observation of the macula via OCT.
• Examination time as a quality indicator of screening upper gastrointestinal endoscopy for asymptomatic examinees

  Takuji Kawamura, Hironori Wada, Naokuni Sakiyama, Yuki Ueda, Atsushi Shirakawa, Yusuke Okada, Kasumi Sanada, Kojiro Nakase, Koichiro Mandai, Azumi Suzuki, Mai Kamaguchi, Atsuhiro Morita, Kenichi Nishioji, Kiyohito Tanaka, Naomi Mochizuki, Koji Uno, Isao Yokota, Masao Kobayashi, Kenjiro Yasuda

  DIGESTIVE ENDOSCOPY 29 5 569 - 575 2017年07月 [査読有り][通常論文]
   

  Background and AimThe significance of examination time of esophagogastroduodenoscopy (EGD) for asymptomatic examinees is yet to be established. We aimed to clarify whether endoscopists who allot more examination time can detect higher numbers of neoplastic lesions among asymptomatic examinees. MethodsWe reviewed a database of consecutive examinees who underwent EGD in our hospital from April 2010 to September 2015. Staff endoscopists were classified into fast, moderate, and slow groups based on the mean examination time of EGD without a biopsy. Neoplastic lesion detection rate among these groups was compared using multiple logistic regression. ResultsOf the 55 786 consecutive examinees who underwent EGD, 15 763 asymptomatic examinees who were screened by staff doctors were analyzed. Mean examination time of 13 661 EGD without biopsy was 6.2 min (range, 2-18 min). When cut-off times of 5 and 7 min were used, four endoscopists were classified into the fast (mean duration, 4.4 1.0 min), 12 into the moderate (6.1 +/- 1.4 min), and four into the slow (7.8 +/- 1.9 min) groups. Neoplastic lesion detection rates in the fast, moderate, and slow groups were 0.57% (13/2288), 0.97% (99/10 180), and 0.94% (31/3295), respectively. Compared with that in the fast group, odds ratios for the neoplastic lesion detection rate in the moderate and slow groups were 1.90 (95% confidence interval [CI], 1.06-3.40) and 1.89 (95% CI, 0.98-3.64), respectively. ConclusionEndoscopists who do not allot adequate examination time may overlook neoplastic lesions in the upper gastrointestinal tract.
• Adjuvant Capecitabine for Breast Cancer after Preoperative Chemotherapy

  N. Masuda, S. -J. Lee, S. Ohtani, Y. -H. Im, E. -S. Lee, I. Yokota, K. Kuroi, S. -A. Im, B. -W. Park, S. -B. Kim, Y. Yanagita, S. Ohno, S. Takao, K. Aogi, H. Iwata, J. Jeong, A. Kim, K. -H. Park, H. Sasano, Y. Ohashi, M. Toi

  NEW ENGLAND JOURNAL OF MEDICINE 376 22 2147 - 2159 2017年06月 [査読有り][通常論文]
   

  BACKGROUND Patients who have residual invasive carcinoma after the receipt of neoadjuvant chemotherapy for human epidermal growth factor receptor 2 (HER2)-negative breast cancer have poor prognoses. The benefit of adjuvant chemotherapy in these patients remains unclear. METHODS We randomly assigned 910 patients with HER2-negative residual invasive breast cancer after neoadjuvant chemotherapy (containing anthracycline, taxane, or both) to receive standard postsurgical treatment either with capecitabine or without (control). The primary end point was disease-free survival. Secondary end points included overall survival. RESULTS The result of the prespecified interim analysis met the primary end point, so this trial was terminated early. The final analysis showed that disease-free survival was longer in the capecitabine group than in the control group (74.1% vs. 67.6% of the patients were alive and free from recurrence or second cancer at 5 years; hazard ratio for recurrence, second cancer, or death, 0.70; 95% confidence interval [CI], 0.53 to 0.92; P=0.01). Overall survival was longer in the capecitabine group than in the control group (89.2% vs. 83.6% of the patients were alive at 5 years; hazard ratio for death, 0.59; 95% CI, 0.39 to 0.90; P=0.01). Among patients with triple-negative disease, the rate of disease-free survival was 69.8% in the capecitabine group versus 56.1% in the control group (hazard ratio for recurrence, second cancer, or death, 0.58; 95% CI, 0.39 to 0.87), and the overall survival rate was 78.8% versus 70.3% (hazard ratio for death, 0.52; 95% CI, 0.30 to 0.90). The hand-foot syndrome, the most common adverse reaction to capecitabine, occurred in 73.4% of the patients in the capecitabine group. CONCLUSIONS After standard neoadjuvant chemotherapy containing anthracycline, taxane, or both, the addition of adjuvant capecitabine therapy was safe and effective in prolonging disease-free survival and overall survival among patients with HER2-negative breast cancer who had residual invasive disease on pathological testing. (Funded by the Advanced Clinical Research Organization and the Japan Breast Cancer Research Group; CREATE-X UMIN Clinical Trials Registry number, UMIN000000843.)
• Cystoid Macular Edema after Descemet's Stripping Automated Endothelial Keratoplasty.

  Koji Kitazawa, Kanae Kayukawa, Koichi Wakimasu, Isao Yokota, Tsutomu Inatomi, Osamu Hieda, Kazuhiko Mori, Chie Sotozono, Shigeru Kinoshita

  Ophthalmology 124 4 572 - 573 2017年04月 [査読有り][通常論文]
  
• Multicenter, randomized, open-label Phase II study comparing S-1 alternate-day oral therapy with the standard daily regimen as a first-line treatment in patients with unresectable advanced pancreatic cancer

  Hiroki Yamaue, Atsushi Shimizu, Yasuhiro Hagiwara, Masayuki Sho, Hiroaki Yanagimoto, Shoji Nakamori, Hideki Ueno, Hiroshi Ishii, Masayuki Kitano, Kazuya Sugimori, Hiroyuki Maguchi, Shinichi Ohkawa, Hiroshi Imaoka, Daisuke Hashimoto, Kazuki Ueda, Hiroko Nebiki, Tatsuya Nagakawa, Hiroyuki Isayama, Isao Yokota, Yasuo Ohashi, Tetsuhiko Shirasaka

  CANCER CHEMOTHERAPY AND PHARMACOLOGY 79 4 813 - 823 2017年04月 [査読有り][通常論文]
   

  Non-inferiority for overall survival (OS) following alternate-day treatment with the oral anticancer drug S-1 compared with standard daily treatment was assessed in Japanese patients with unresectable advanced pancreatic cancer in a multicenter, randomized, phase II study. This trial was registered at the UMIN Clinical Trials Registry (no. 000008604). Chemotherapy-na < ve patients with locally advanced or metastatic pancreatic cancer were randomly assigned 2:1 to treatment with alternate-day (twice daily on alternate days from days 1 through 42 of a 42-day cycle) or daily (twice daily on days 1 through 28 of a 42-day cycle) treatment with S-1. The primary endpoint was OS. Secondary endpoints were progression-free survival (PFS), time to treatment failure, response rate, quality of life assessments, and safety. A total of 190 patients were enrolled, of which 185 were included in the final analysis (alternate-day: 121; daily: 64). Median OS was 9.4 for the alternate-day group and 10.4 months for the daily group [hazard ratio (HR), 1.19; 95% credible interval, 0.86 to 1.64], indicating that non-inferiority of alternate-day treatment to daily treatment was not demonstrated. Median PFS was 3.0 for the alternate-day group and 4.2 months for the daily group (HR, 1.65; 95% credible interval, 1.20-2.29). The incidence of anorexia, fatigue, neutrophils, pigmentation, and pneumonitis was lower in alternate-day treatment compared with daily treatment. S-1 for advanced pancreatic cancer should be taken daily as recommended, based on the decreased OS and PFS and marginal improvement in safety observed in the alternate-day group.
• Olmesartan with azelnidipine versus with trichlormethiazide on home blood pressure variability in patients with type II diabetes mellitus

  Emi Ushigome, Shinobu Matsumoto, Chikako Oyabu, Hidetaka Ushigome, Isao Yokota, Goji Hasegawa, Naoto Nakamura, Muhei Tanaka, Masahiro Yamazaki, Michiaki Fukui

  JOURNAL OF THE AMERICAN SOCIETY OF HYPERTENSION 11 3 140 - 147 2017年03月 [査読有り][通常論文]
   

  The aim of the present study was to compare the effects of olmesartan combined with azelnidipine versus olmesartan combined with trichlormethiazide, on home blood pressure (BP) and pressure variability in type II diabetes mellitus patients using home BP telemonitoring system. We performed an open-label cross-over pilot study of 28 patients with type II diabetes mellitus. Patients received combination treatment with either olmesartan 20 mg plus azelnidipine 16 mg or olmesartan 20 mg plus trichlormethiazide 1 mg for more than 6 weeks each in a cross-over method. The coefficient of morning systolic BP variability in the olmesartan plus azelnidipine group was significantly lower than that in the olmesartan plus trichlormethiazide group (6.4 +/- 1.9 vs. 7.5 +/- 2.6, P =.004). There were no significant differences in mean morning systolic BP between the two groups. Using home BP telemonitoring for hypertensive patients with type II diabetes, this study revealed for the first time that the olmesartan with azelnidipine combination is superior to the olmesartan with trichlormethiazide combination in reducing home BP variability. J Am Soc Hypertens Copyright (C) 2016 American Society of Hypertension. All rights reserved.
• Curtain osteophytes are one of the risk factors for the poor outcome of rotational acetabular osteotomy

  Shiho Kanezaki, Shigeru Nakamura, Masaki Nakamura, Isao Yokota, Takashi Matsushita

  INTERNATIONAL ORTHOPAEDICS 41 2 265 - 270 2017年02月 [査読有り][通常論文]
   

  Purpose Rotational acetabular osteotomy (RAO) is one of the surgical procedures for painful dysplastic hips. Although several risk factors for poor outcome of RAO have been reported, the presence of a curtain osteophyte in the acetabulum has not been evaluated as a possible risk factor. This study aimed to analyze the risk factors affecting the outcome of RAO and to clarify whether curtain osteophytes are one of the risk factors. Methods We retrospectively analyzed 87 hips in 78 patients with a mean age of 36 (range, 13-54) years. The mean follow-up period was 8.3 (range, 2.1-19.5) years. The radiographic severity of osteoarthritis was classified into four stages: pre-arthrosis, initial stage, advanced stage, and terminal stage. The Japanese Orthopaedic Association (JOA) hip score was used for clinical evaluation. Poor outcome was defined as a hip with a JOA score < 80 points or terminal-stage osteoarthritis at final follow-up. Several factors were evaluated by logistic regression analysis. Results At final follow-up, ten hips had a JOA score < 80 and nine hips had progressed to terminal-stage osteoarthritis. Since five hips had a JOA score < 80 as well as terminal-stage osteoarthritis, a total of 14 hips were determined to have poor outcome. An additional ten years of age at surgery, pre-operative minimal joint space < 2 mm, presence of a curtain osteophyte, and fair/poor congruency in abduction were identified as significant risk factors for poor outcome of RAO. Conclusions Hips with curtain osteophyte should be evaluated carefully before RAO.
• Complete adherence to evidence-based quality-of-care indicators for Staphylococcus aureus bacteremia resulted in better prognosis.

  Miki Nagao, Masaki Yamamoto, Yasufumi Matsumura, Isao Yokota, Shunji Takakura, Satoshi Teramukai, Satoshi Ichiyama

  Infection 45 1 83 - 91 2017年02月 [査読有り][通常論文]
   

  PURPOSE: Staphylococcus aureus bacteremia (SAB) is a serious clinical condition associated with high morbidity and mortality. Recent studies have revealed that adherence to evidence-based quality-of-care indicators (QCIs) for the management of SAB could result in reduced mortality. We aimed to determine whether compliance with QCIs was associated with mortality and whether compliance with QCIs predicted the mortality of patients with SAB. METHODS: In a university hospital in Kyoto, Japan, SAB patients, who survived at least 14 days after positive blood cultures were analyzed from 2006 to 2014 to assess their compliance with QCIs and the trend in mortality. In addition, the predicted mortality, which was stratified by the number of fulfilled QCIs (QCI points), was calculated. In this study, the following five main QCI points were evaluated: (1) follow-up blood cultures; (2) early source control when applicable; (3) echocardiography; (4) the early use of appropriate antibiotics, and (5) the appropriate duration of therapy. RESULTS: We identified 477 eligible SAB cases, of which 199 were MRSA cases (41.7 %). The proportion of SAB cases in which the physicians adhered to at least four QCIs increased gradually from 47.5 % in 2006 to 79.3 % in 2014 (P = 0.001); whereas, the 30-day mortality decreased from 10.0 to 3.4 % after treatment completion. CONCLUSIONS: With an increase in the proportion of SAB cases adhering to QCIs, better prognoses were observed for patients with SAB. The QCI points reflected the 30-day mortality.
• Gait Performance Trajectories and Incident Disabling Dementia Among Community-Dwelling Older Japanese

  Yu Taniguchi, Akihiko Kitamura, Satoshi Seino, Hiroshi Murayama, Hidenori Amano, Yu Nofuji, Mariko Nishi, Yuri Yokoyama, Tomohiro Shinozaki, Isao Yokota, Yutaka Matsuyama, Yoshinori Fujiwara, Shoji Shinkai

  JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION 18 2 192.e13 - 192.e20 2017年02月 [査読有り][通常論文]
   

  Objectives: Initial gait speed is a good predictor of dementia in later life. This prospective study used repeated measures analysis to identify potential gait performance trajectory patterns and to determine whether gait performance trajectory patterns were associated with incident disabling dementia among community-dwelling older Japanese. Design: A prospective, observational, population-based follow-up study. Setting: Japan, 2002 to 2014. Participants: A total of 1686 adults without dementia (mean [SD] age, 71.2 [5.6] years; women, 56.3%) aged 65 to 90 years participated in annual geriatric health assessments during the period from June 2002 through July 2014. The average number of follow-up assessments was 3.9, and the total number of observations was 6509. Measurements: Gait performance was assessed by measuring gait speed and step length at usual and maximum paces. A review of municipal databases in the Japanese public long-term care insurance system revealed that 196 (11.6%) participants developed disabling dementia through December 2014. Results: We identified 3 distinct trajectory patterns ( high, middle, and low) in gait speed and step length at usual and maximum paces in adults aged 65 to 90 years; these trajectory patterns showed parallel declines among men and women. After adjusting for important confounders, participants in the low trajectory groups for gait speed and step length at usual pace were 3.46 ( 95% confidence interval 1.88 -6.40) and 2.12 (1.29-3.49) times as likely to develop incident disabling dementia, respectively, as those in the high trajectory group. The respective values for low trajectories of gait speed and step length at maximum pace were 2.05 (1.02-4.14) and 2.80 (1.48-5.28), respectively. Conclusions: Regardless of baseline level, the 3 major trajectory patterns for gait speed and step length tended to show similar age-related changes in men and women in later life. Individuals with low trajectories for gait speed and step length had a higher dementia risk, which highlights the importance of interventions for improvements in gait performance, even among older adults with low gait performance. (c) 2016 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
• Acquired Exchange Protein Directly Activated by Cyclic Adenosine Monophosphate Activity Induced by p38 Mitogen-activated Protein Kinase in Primary Afferent Neurons Contributes to Sustaining Postincisional Nociception

  Megumi Matsuda, Kentaro Oh-Hashi, Isao Yokota, Teiji Sawa, Fumimasa Amaya

  ANESTHESIOLOGY 126 1 150 - 162 2017年01月 [査読有り][通常論文]
   

  Background: The molecular mechanisms responsible for sustained pain after tissue injury are largely unknown. The aim of this study was to clarify the role of exchange protein directly activated by cyclic adenosine monophosphate (EPAC) in sustained postincisional nociception, using tissue injury-induced nociceptor priming, and involvement of p38 mitogen-activated protein kinase (p38MAPK) in EPAC-mediated nociceptor priming. Methods: Plantar incisions were made in the hind paws of Sprague-Dawley rats (n = 144). Nociceptor priming was confirmed by behavior testing followed by prostaglandin E2 injection 14 to 21 days after the incision. ESI-09, a selective EPAC inhibitor, was administered to assess its effects on nociceptor priming. Expression of two isoforms of EPAC (EPAC1/EPAC2) in dorsal root ganglions from naive rats and those 14 days after the incision was detected by immunohistochemistry and Western blotting. Separately, FR167653, a selective p38MAPK inhibitor, was administered to assess its effect on EPAC1/EPAC2 expression and the development of nociceptor priming. Results: Prostaglandin E2 injection 14 to 21 days after the plantar incision induced persistent mechanical hyperalgesia for 7 days. EPAC1/EPAC2 expression in dorsal root ganglion neurons was trivial in naive rats (7.7 +/- 4.8% for EPAC1; 6.3 +/- 4.1% for EPAC2) but markedly increased 14 days after the incision (21.0 +/- 9.4% and 20.1 +/- 3.8%, respectively). ESI-09 treatment inhibited prostaglandin E2-induced persistent mechanical hypersensitivity but had no effect on incision-induced acute nociceptive hypersensitivity. Treatment with FR167653 before the incision inhibited the development of nociceptor priming and incision-induced EPAC1/EPAC2 expression (8.5 +/- 5.4% and 7.6 +/- 3.3%, respectively). Conclusions: Transient inflammatory stimulation causes long-lasting nociceptive hypersensitivity via nociceptor priming during the subacute period after incision. Acquired EPAC activity by p38MAPK in the dorsal root ganglion neurons is a key for this event.
• Validity of the Short Nutritional Assessment Questionnaire for Japanese Patients with Cancer Undergoing Outpatient Chemotherapy.

  Kiyomi Harada, Kiyo Ochi, Tetsuya Taguchi, Terukazu Nakamura, Motohiro Kanazawa, Naohisa Yoshida, Hiroko Neriya, Masami Okagaki, Naoko Nishida, Yukie Takishita, Yoko Yamamoto, Sayori Wada, Masashi Kuwahata, Isao Yokota, Keiko Sekido, Akane Higashi

  The journal of medical investigation : JMI 64 1.2 117 - 121 2017年 [査読有り][通常論文]
   

  PURPOSE: To investigate the utility of the Short Nutritional Assessment Questionnaire (SNAQ) in the nutritional evaluation of patients with cancer undergoing outpatient chemotherapy. METHODS: We included 229 patients with cancer who were undergoing outpatient chemotherapy between October 2015 and April 2016. The SNAQ and the revised SNAQ (addition of age and body mass index) were implemented, and their relationships with Controlling Nutritional Status (CONUT), an indicator of bionutritional assessment, were examined. RESULTS: The cutoff value of the SNAQ score corresponding to moderate-to-severe undernourishment in CONUT values was 0.5, with a sensitivity of 87.5% and a specificity of 65.9%, and the corresponding values for the revised SNAQ score were 2.5, 91.7%, and 62.9%, respectively. This cutoff value and the corresponding positive prediction value for the revised SNAQ were superior to those of SNAQ. Binary logistic regression analysis with the revised SNAQ and sex as independent variables and the CONUT value as the dependent variable revealed that the higher the SNAQ score, the more likely it was that CONUT moderate-to-severe undernourishment would be identified (odds ratio, 1.48;, 1.34-1.96). CONCLUSION: Nutritional evaluation with the revised SNAQ can predict moderate-to-severe undernourishment according to CONUT in patients with cancer undergoing outpatient chemotherapy. J. Med. Invest. 64: 117-121, February, 2017.
• Evaluation of the severity of capsular contracture using elastography after breast implant reconstruction

  Yoshihiro Sowa, Isao Yokota, Sizu Itsukage, Katsuhiko Nakatsukasa, Koichi Sakaguchi, Tetsuya Taguchi, Toshiaki Numajiri

  CLINICAL HEMORHEOLOGY AND MICROCIRCULATION 66 1 1 - 6 2017年 [査読有り][通常論文]
   

  BACKGROUND: Capsular contracture around implants is a common complication after breast reconstruction. Strain elastography (STE) and shear-wave elastography (SWE) are noninvasive imaging techniques that can measure tissue stiffness and thickness of the capsule. OBJECTIVE: The purposes of the study were to compare STE and SWE for measurement of capsular contracture after breast implant reconstruction using intra-class correlation coefficients (ICCs) and to investigate the correlation of these data with the Baker score, which is the most frequently used clinical staging scale for capsule contracture. METHODS: The subjects were 20 patients (27 implants) who underwent breast reconstruction. RESULTS: The reproducibility of SWE (ICC: 0.878) was higher than that of STE (ICC: 0.724) for measurement of capsular contracture. The correlation coefficient between measurements with the two methods was low (r = 0.6788). The Baker score had a higher correlation with measurements with SWE (r = 0.8124) compared to those with STE (r = 0.6983). CONCLUSIONS: These results suggest that SWE is a better tool for assessment of the degree of capsule contracture surrounding implants after breast reconstruction.
• Prospective Study of Trajectories of Physical Performance and Mortality Among Community-Dwelling Older Japanese

  Yu Taniguchi, Yoshinori Fujiwara, Hiroshi Murayama, Isao Yokota, Eri Matsuo, Satoshi Seino, Yu Nofuji, Mariko Nishi, Yutaka Matsuyama, Shoji Shinkai

  JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES 71 11 1492 - 1499 2016年11月 [査読有り][通常論文]
   

  Physical performance measures (PPMs) are good predictors of adverse health outcomes in later life. This prospective study used repeated measures analysis to examine sex-specific age trends in PPMs, identify potential PPM trajectory patterns, and determine whether PPM trajectory patterns were associated with all-cause mortality among older Japanese. Among 1,524 adults aged 65 years or older who participated in a baseline survey, 1,048 adults (mean [SD] age, 71.6 [5.4] years; women, 57.0%) were followed up at least once. The total number of observations was 4,747, and the average number of follow-up assessments was 4.5 during the period from 2002 through 2011. The PPMs studied were handgrip strength, usual gait speed, and one-leg standing time. We checked local registries to identify deaths from any cause; 89 (8.5%) participants died during follow-up. All PPMs significantly decreased with advancing age, and handgrip strength and usual gait speed showed sex-specific age trends. We identified three distinct trajectory patterns (high, middle, and low trajectory groups) for each PPM in adults aged 65-90 years, and the trajectories for handgrip strength and usual gait speed showed parallel declines in men and women, respectively. After adjusting for important confounders, the trajectory groups for handgrip strength and one-leg standing time were independent predictors of all-cause mortality. Regardless of baseline level, the PPMs tended to show similar age-related changes in later life. However, individuals in low PPM trajectory groups had a higher mortality risk, which highlights the importance of interventions that maintain or improve physical performance, even among older adults with low physical performance.
• A Simple Risk Stratification Model for ST-Elevation Myocardial Infarction (STEMI) from the Combination of Blood Examination Variables: Acute Myocardial Infarction-Kyoto Multi-Center Risk Study Group

  Kenji Yanishi, Takeshi Nakamura, Naohiko Nakanishi, Isao Yokota, Kan Zen, Tetsuhiro Yamano, Hirokazu Shiraishi, Takeshi Shirayama, Jun Shiraishi, Takahisa Sawada, Yoshio Kohno, Makoto Kitamura, Keizo Furukawa, Satoaki Matoba

  PLOS ONE 11 11 e0166391  2016年11月 [査読有り][通常論文]
   

  Background Many mortality risk scoring tools exist among patients with ST-elevation Myocardial Infarction (STEMI). A risk stratification model that evaluates STEMI prognosis more simply and rapidly is preferred in clinical practice. Methods and Findings We developed a simple stratification model for blood examination by using the STEMI data of AMI-Kyoto registry in the derivation set (n = 1,060) and assessed its utility for mortality prediction in the validation set (n = 521). We selected five variables that significantly worsen in-hospital mortality: white blood cell count, hemoglobin, C-reactive protein, creatinine, and blood sugar levels at >10,000/mu L, <10 g/dL, >1.0 mg/dL, >1.0 mg/dL, and >200 mg/dL, respectively. In the derivation set, each of the five variables significantly worsened inhospital mortality (p < 0.01). We developed the risk stratification model by combining laboratory variables that were scored based on each beta coefficient obtained using multivariate analysis and divided three laboratory groups. We also found a significant trend in the inhospital mortality rate for three laboratory groups. Therefore, we assessed the utility of this model in the validation set. The prognostic discriminatory capacity of our laboratory stratification model was comparable to that of the full multivariable model (c-statistic: derivation set vs validation set, 0.81 vs 0.74). In addition, we divided all cases (n = 1,581) into three thrombolysis in myocardial infarction (TIMI) risk index groups based on an In TIME II sub-study; the cases were further subdivided based on this laboratory model. The high laboratory group had significantly high in-hospital mortality rate in each TIMI risk index group (trend of in-hospital mortality; p < 0.01). Conclusions This laboratory stratification model can predict in-hospital mortality of STEMI simply and rapidly and might be useful for predicting in-hospital mortality of STEMI by further subdividing the TIMI risk index.
• A Novel Diagnostic and Prognostic Biomarker Panel for Endothelial Cell Damage-Related Complications in Allogeneic Transplantation.

  Shotaro Tatekawa, Akio Kohno, Kazutaka Ozeki, Koichi Watamoto, Norihiro Ueda, Yohei Yamaguchi, Tsutomu Kobayashi, Isao Yokota, Satoshi Teramukai, Masafumi Taniwaki, Junya Kuroda, Yoshihisa Morishita

  Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation 22 9 1573 - 1581 2016年09月 [査読有り][通常論文]
   

  Noninfectious transplantation-related complications (TRCs), such as graft-versus-host disease or TRC with endothelial cell damage (TRC-EC), remain as the major obstacle for successful allogeneic hematopoietic cell transplantation (allo-HCT). However, the diagnosis and prognosis for the emergence of these complications are difficult to define during the early post allo-HCT period. Here, we tried to generate a novel diagnostic system for TRC-EC by analyzing 188 adult patients who received allo-HCT. Our study found that the peripheral blood levels of angiopoietin 2 (ANG2), C-reactive protein (CRP), D-dimer, and thrombomodulin (TM) at the onset of TRCs were significantly associated with the development of TRC-EC. We next developed a composite biomarker panel incorporating the risk values of ANG2, CRP, D-dimer, and TM at the onset of TRCs, which classified these patients into 3 risk groups: low, intermediate, and high risk. As a result, the panel was useful not only for the diagnosis of TRC-EC with high specificity and sensitivity, but also for the prediction of the patients' long-term outcome. The 5-year overall survival (OS) rates of patients in the low-, intermediate-, and high-risk groups since the occurrence from TRCs were 76.2%, 54.9%, and 26.9%, respectively, and the high-risk score was significantly associated with both poor OS (hazard ratio [HR], 5.60; 95% confidence interval [CI], 2.81 to 11.20; P < .01) and frequent nonrelapse mortality (HR, 19.75; 95% CI, 5.59 to 69.77; P < .01). Thus, the composite panel proposed in this study provides a powerful tool for the diagnosis of TRC-EC and for the prediction of survival for patients with TRC-EC after allo-HCT.
• Measurement of Corneal Endothelial Surface Area Using Anterior Segment Optical Coherence Tomography in Normal Subjects

  Koji Kitazawa, Isao Yokota, Chie Sotozono, Shigeru Kinoshita

  CORNEA 35 9 1229 - 1233 2016年09月 [査読有り][通常論文]
   

  Purpose: To calculate the number of corneal endothelial cells (CEC) on the posterior surface of the normal human cornea by measuring specific surface areas through anterior segment optical coherence tomography. The effects of age, sex, and variations between the right and left eyes were also investigated.Methods: This study involved 60 eyes of 30 normal subjects with no history of corneal disease. Subjects were divided into the following groups according to age: group A (20-39 years old), group B (40-59 years old), and group C (60-79 years old). Set areas of the corneal posterior surface were imaged and analyzed using anterior segment optical coherence tomography, and the number of CECs was calculated based on the area measured and a CEC density.Results: The posterior corneal surface area measured within the central circular diameters of 10.2, 8.5, and 7.5 mm was 86.8, 63.8, and 48.4 mm(2) in group A, 86.0, 63.8, and 48.4 mm(2) in group B, and 87.0, 64.2, and 48.6 mm(2) in group C, respectively. The total number of CECs on the posterior surface in the diameters of 10.2, 8.5, and 7.5 mm was 2.3 x 10(5), 1.7 x 10(5), and 1.3 x 10(5), respectively. No clinically relevant differences in the posterior surface were found in relation to age, sex, or variation between right and left eyes.Conclusions: Calculation of the CEC number on the corneal posterior surface is essential for determining the number of cells applied during penetrating keratoplasty, endothelial keratoplasty, or cultivated CEC injection therapy when available.
• Comparative Study of Seven-year Outcomes Following Laser In Situ Keratomileusis with those of Trans-epithelial Photorefractive Keratectomy.

  Nakamura Y, Hieda O, Yamamura K, Wakimasu K, Yokota I, Kinoshita S

  Nippon Ganka Gakkai zasshi 120 7 487 - 493 日本眼科学会 2016年07月 [査読有り][通常論文]
  
• The correlation between the change of distal motor latency of the median nerve and the abundant A-waves in Guillain-Barré syndrome.

  Kadoya A, Ogawa G, Kawakami S, Yokota I, Hatanaka Y, Uchibori A, Chiba A, Sonoo M

  Journal of neurology, neurosurgery, and psychiatry 87 4 444 - + 2016年04月 [査読有り][通常論文]
  
• Does hand dominance affect peripheral nerve excitability?

  Yukiko Tsuji, Yu-ichi Noto, Kensuke Shiga, Isao Yokota, Masanori Nakagawa, Toshiki Mizuno

  CLINICAL NEUROPHYSIOLOGY 127 4 1921 - 1922 2016年04月 [査読有り][通常論文]
  
• Evaluation of factors associated with psychiatric patient dropout at a university outpatient clinic in Japan

  Atsumi Minamisawa, Jin Narumoto, Isao Yokota, Kenji Fukui

  PATIENT PREFERENCE AND ADHERENCE 10 1903 - 1911 2016年 [査読有り][通常論文]
   

  Background: Patient dropout from treatment can lead to a deterioration in clinical condition, thereby increasing the need for more intensive therapy that incurs substantial social and economic losses. The aim of this study was to identify factors related to psychiatric patient dropout at a university outpatient clinic in Japan. Methods: We retrospectively examined the medical charts of new psychiatric patients who were diagnosed with either a mood disorder (International Classification of Diseases, 10th revision, code: F3) or an anxiety disorder (F4) in the outpatient clinic at Kyoto Prefectural University of Medicine Hospital in Kyoto, Japan, between April 2010 and March 2013. The baseline characteristics of the patients (age, sex, Global Assessment of Functioning score, Clinical Global Impression-Severity of Illness score, education, occupation, marital status, duration of treatment, and prior treatment history), treating psychiatrist experience in years, and sex concordance between the patients and their treating psychiatrists were analyzed using Cox regression models. Results: From among 1,626 eligible new patients during the study period, 532 patients were enrolled in the study (F3: n=176; F4: n=356). The dropout rate was 35.7%, which was similar to that of previous studies. Higher educational level, being married, and lower Global Assessment of Functioning scores were associated with a lower dropout rate. Although psychiatrist experience was not significantly associated with patient dropout in the multivariate analysis, patients treated by less experienced psychiatrists had a higher hazard ratio for dropout (1.31; 95% confidence interval: 0.94-1.85). Conclusion: In order to reduce the dropout rate, special focus should be placed on patients with the factors identified in this study, and young psychiatrists should undergo further education to foster adherence.
• The Kyoto Prognostic Index for Patients with Diffuse Large B-Cell Lymphoma in the Rituximab Era

  Tsutomu Kobayashi, Junya Kuroda, Isao Yokota, Kazuna Tanba, Tomohiko Taki, Takahiro Fujino, Saeko Kuwahara, Reiko Isa, Junko Yamaguchi, Eri Kawata, Teruaki Akaogi, Hitoji Uchiyama, Hiroto Kaneko, Nobuhiko Uoshima, Yutaka Kobayashi, Satoshi Teramukai, Masafumi Taniwaki

  BLOOD 126 23 2015年12月 [査読有り][通常論文]
  
• Novel prediction model of renal function after nephrectomy from automated renal volumetry with preoperative multidetector computed tomography (MDCT)

  Shuji Isotani, Hirofumi Shimoyama, Isao Yokota, Yasuhiro Noma, Kousuke Kitamura, Toshiyuki China, Keisuke Saito, Shin-ichi Hisasue, Hisamitsu Ide, Satoru Muto, Raizo Yamaguchi, Osamu Ukimura, Inderbir S. Gill, Shigeo Horie

  CLINICAL AND EXPERIMENTAL NEPHROLOGY 19 5 974 - 981 2015年10月 [査読有り][通常論文]
   

  The predictive model of postoperative renal function may impact on planning nephrectomy. To develop the novel predictive model using combination of clinical indices with computer volumetry to measure the preserved renal cortex volume (RCV) using multidetector computed tomography (MDCT), and to prospectively validate performance of the model. Total 60 patients undergoing radical nephrectomy from 2011 to 2013 participated, including a development cohort of 39 patients and an external validation cohort of 21 patients. RCV was calculated by voxel count using software (Vincent, FUJIFILM). Renal function before and after radical nephrectomy was assessed via the estimated glomerular filtration rate (eGFR). Factors affecting postoperative eGFR were examined by regression analysis to develop the novel model for predicting postoperative eGFR with a backward elimination method. The predictive model was externally validated and the performance of the model was compared with that of the previously reported models. The postoperative eGFR value was associated with age, preoperative eGFR, preserved renal parenchymal volume (RPV), preserved RCV, % of RPV alteration, and % of RCV alteration (p < 0.01). The significant correlated variables for %eGFR alteration were %RCV preservation (r = 0.58, p < 0.01) and %RPV preservation (r = 0.54, p < 0.01). We developed our regression model as follows: postoperative eGFR = 57.87 - 0.55(age) - 15.01(body surface area) + 0.30(preoperative eGFR) + 52.92(%RCV preservation). Strong correlation was seen between postoperative eGFR and the calculated estimation model (r = 0.83; p < 0.001). The external validation cohort (n = 21) showed our model outperformed previously reported models. Combining MDCT renal volumetry and clinical indices might yield an important tool for predicting postoperative renal function.
• Feasibility and accuracy of computational robot-assisted partial nephrectomy planning by virtual partial nephrectomy analysis

  Shuji Isotani, Hirofumi Shimoyama, Isao Yokota, Toshiyuki China, Shin-ichi Hisasue, Hisamitsu Ide, Satoru Muto, Raizo Yamaguchi, Osamu Ukimura, Shigeo Horie

  International Journal of Urology 22 5 439 - 446 2015年05月01日 [査読有り][通常論文]
   

  Objectives: To evaluate the feasibility and accuracy of virtual partial nephrectomy analysis, including a color-coded three-dimensional virtual surgical planning and a quantitative functional analysis, in predicting the surgical outcomes of robot-assisted partial nephrectomy. Methods: Between 2012 and 2014, 20 patients underwent virtual partial nephrectomy analysis before undergoing robot-assisted partial nephrectomy. Virtual partial nephrectomy analysis was carried out with the following steps: (i) evaluation of the arterial branch for selective clamping by showing the vascular-supplied area (ii) simulation of the optimal surgical margin in precise segmented three-dimensional model for prediction of collecting system opening and (iii) detailed volumetric analyses and estimates of postoperative renal function based on volumetric change. At operation, the surgeon identified the targeted artery and determined the surgical margin according to the virtual partial nephrectomy analysis. The surgical outcomes between the virtual partial nephrectomy analysis and the actual robot-assisted partial nephrectomy were compared. Results: All 20 patients had negative cancer surgical margins and no urological complications. The tumor-specific renal arterial supply areas were shown in color-coded three-dimensional model visualization in all cases. The prediction value of collecting system opening was 85.7% for sensitivity and 100% for specificity. The predicted renal resection volume was significantly correlated with actual resected specimen volume (r2=0.745, P< 0.001). The predicted estimated glomerular filtration rate was significantly correlated with actual postoperative estimated glomerular filtration rate (r2=0.736, P< 0.001). Conclusions: Virtual partial nephrectomy analysis is able to provide the identification of tumor-specific renal arterial supply, prediction of collecting system opening and prediction of postoperative renal function. This technique might allow urologists to compare various arterial clamping methods and resection margins with surgical outcomes in a non-invasive manner.
• 繰り返しイベントデータに対する動的予測 -動的擬似値を用いたランドマークアプローチ-

  横田 勲

  東京大学 2015年03月 [査読有り][通常論文]
  
• Feasibility of multiparametric prostate magnetic resonance imaging in the detection of cancer distribution: histopathological correlation with prostatectomy specimens.

  Kitamura K, Muto S, Yokota I, Hoshimoto K, Kaminaga T, Noguchi T, Sugiura S, Ide H, Yamaguchi R, Furui S, Horie S

  Prostate international 2 4 188 - 195 2014年12月 [査読有り][通常論文]
   

  PURPOSE: To prevent overtreatment, it is very important to diagnose the precise distribution and characteristics of all cancer lesions, including small daughter tumors. The purpose of this study was to evaluate the efficacy of T2-weighted magnetic resonance imaging (T2W), diffusion-weighted magnetic resonance imaging (DWI), magnetic resonance spectroscopy ((1)H-MRS), and prostate biopsy (PBx) in the detection of intraprostatic cancer distribution. METHODS: All patients underwent T2W, DWI, (1)H-MRS, and PBx followed by radical prostatectomy (RP). Individual prostates were divided into 12 segmental regions, each of which was examined for the presence or absence of malignancy on the basis of T2W, DWI, (1)H-MRS, and PBx, respectively. These results were compared with the histopathological findings for RP specimens. RESULTS: We included 54 consecutive patients with biopsy-proven prostate cancer (mean age, 62.7 years; median prostate-specific antigen level, 5.7 ng/mL) in this study. We could detect cancer in 247 of 540 evaluable lesions. The area under the receiver operator characteristic curve analysis yielded a higher value for DWI (0.68) than for T2W (0.65), (1)H-MRS (0.54), or PBx (0.56). In 180 cancerous regions of RP specimens with false-negative PBx results, T2W+DWI had the highest positive rate (53.3%) compared with that of each sequence alone, including T2W (45.6%), DWI (41.1%), and (1)H-MRS (30.0%). CONCLUSIONS: Multiparametric magnetic resonance imaging (T2W, (1)H-MRS, DWI) enables the detection of prostate cancer distribution with reasonable sensitivity and specificity. T2W+DWI was particularly effective in detecting cancer distribution with false-negative PBx results.
• Anastrozole versus tamoxifen as adjuvant therapy for Japanese postmenopausal patients with hormone-responsive breast cancer: efficacy results of long-term follow-up data from the N-SAS BC 03 trial

  Tomohiko Aihara, Isao Yokota, Yasuo Hozumi, Kenjiro Aogi, Hiroji Iwata, Motoshi Tamura, Atsushi Fukuuchi, Haruhiko Makino, Ryungsa Kim, Masashi Andoh, Koichiro Tsugawa, Shinji Ohno, Takuhiro Yamaguchi, Yasuo Ohashi, Toru Watanabe, Yuichi Takatsuka, Hirofumi Mukai

  BREAST CANCER RESEARCH AND TREATMENT 148 2 337 - 343 2014年11月 [査読有り][通常論文]
   

  Aromatase inhibitors are superior to tamoxifen as adjuvant therapy in postmenopausal patients with hormone-responsive breast cancer. We report the follow-up efficacy results from the N-SAS BC 03 trial (UMIN CTRID: C000000056) where anastrozole was compared with tamoxifen as adjuvant therapy in postmenopausal Japanese patients with hormone-responsive early breast cancer. The full analysis set contained 696 patients (anastrozole arm, n = 345; tamoxifen arm, n = 351). The log-rank test was used to compare the two groups in terms of disease-free survival (DFS) and relapse-free survival (RFS); Kaplan-Meier estimates were calculated. The treatment effects were estimated by Cox's proportional hazards model. To examine time-varying effect of hazard ratios, we estimated time-varying hazard ratios at time t [HR(t)] using data from time t up to 12 months. After a median follow-up of 98.5 months, hazard ratios (95 % CIs) were 0.90 (0.65-1.24; log-rank p = 0.526) for DFS and 0.83 (0.56-1.23; log-rank p = 0.344) for RFS. Hazard ratios (95 % CIs) for DFS and RFS up to 36 months were 0.69 (0.40-1.17) and 0.54 (0.27-1.06) and those after 36 months were 1.06 (0.70-1.59) and 1.05 (0.64-1.73), respectively. Time-varying hazard ratios for both DFS and RFS showed that hazard ratios were initially in favor of anastrozole and approached 1.0 at around 36 months. Superior efficacy of anastrozole to tamoxifen suggested by the initial analysis was not confirmed in the present analysis after a long-term follow-up period. Advantage of anastrozole was the greatest immediately after switching from tamoxifen and then decreased thereafter.
• Prospective Study on the Incidence of Bone Metastasis (BM) and Skeletal-Related Events (SREs) in Patients (pts) with Stage IIIB and IV Lung Cancer-CSP-HOR 13

  Nobuyuki Katakami, Hiroshi Kunikane, Koji Takeda, Koichi Takayama, Toshiyuki Sawa, Hiroshi Saito, Masao Harada, Soichiro Yokota, Kiyoshi Ando, Yuko Saito, Isao Yokota, Yasuo Ohashi, Kenji Eguchi

  JOURNAL OF THORACIC ONCOLOGY 9 2 231 - 238 2014年02月 [査読有り][通常論文]
   

  Background: Bone metastasis (BM) is a frequent complication in patients with advanced lung cancer and it causes skeletal-related events (SREs). Our study aim is to prospectively investigate the incidence of BM, incidence and types of SRE, and predictive factors of BM and SREs. Methods: Newly diagnosed, advanced non-small-cell lung cancer (NSCLC) or small-cell lung cancer (SCLC) patients were enrolled into the study. Patients were followed up every 4 weeks to monitor the development of SREs. Treatment for lung cancer was performed at the discretion of the investigator. Results: Two hundred seventy-four patients were enrolled in this study between April 2007 and December 2009 from 12 institutions. Patients included 77 cases of SCLC and 197 of NSCLC (stage IIIB/IV = 73/124). Median follow-up time was 13.8 months. The incidence of BM at initial diagnosis was 48% in stage IV NSCLC and 40% in extensive stage (ED)-SCLC. Forty-five percent of patients who developed BM had SREs consisting of pathologic fracture (4.7%), radiation to bone (15.3%), spinal cord compression (1.1%), and hypercalcemia (2.2%). Multivariate analysis revealed that factors predicting BM are stage IV, performance status 1 or greater and higher bone alkaline phosphatase in NSCLC patients, higher lactate dehydrogenase, and lower parathyroid hormone-related peptide in SCLC patients. Factors predicting SREs were stage IV, age 64 or younger, and lower albumin in NSCLC patients. Multivariate analysis of SRE was not performed for SCLC because of the small number of events. Conclusion: Predictive factors should be taken into consideration in future randomized studies evaluating BM and SREs.

講演・口頭発表等

• Regression modelling for net chance of a longer survival: pseudo-observation approach  [招待講演]

  Isao Yokota

  WNAR/IMS Annual Meeting 2023 2023年06月 口頭発表（招待・特別）
• 繰り返しイベントに関する回数別発生確率に対するノンパラメトリック推定量の統計的効率

  横田 勲

  2023年度計量生物学会年会 2023年04月
• Test-then-pool法と傾向スコア重み付け法を組み合わせた既存試験データを併合するための二段階アプローチ

  岡田 和史, 横田 勲

  2023年度計量生物学会年会 2023年04月
• Probabilistic index for survival analysis using landmark time, clinically significant differences, and multiple prioritized endpoints: a simulation study

  Kanako Fuyama, Isao Yokota

  ENAR 2023 Spring Meeting 2023年03月
• Exact sequential single-arm trial design with curtailment for binary endpoint

  Tasuku Inao, Isao Yokota

  ENAR 2023 Spring Meeting 2023年03月
• Two one-sided test-then-pool method for clinical trials  [通常講演]

  Kazufumi Okada, Isao Yokota

  43rd Annual Conference of the International Society for Clinical Biostatistics 2022年08月 口頭発表（一般）
• 二値エンドポイントに対する早期中止を行う正確な単群逐次試験デザインの提案  [通常講演]

  稲尾 翼, 横田 勲

  2022年計量生物学会年会 2022年05月
• 右側打ち切りが時点生存割合の有効サンプルサイズに与える影響  [通常講演]

  横田 勲

  2022年計量生物学会年会 2022年05月
• 二値アウトカムにおける逐次検定手法の性能比較  [通常講演]

  稲尾 翼, 横田 勲

  2021年度日本分類学会シンポジウム 2021年12月
• 中点代入法を用いた区間打ち切りデータに対する境界内平均生存時間の推定  [通常講演]

  大倉 裕希, 稲尾 翼, 横田 勲

  2021年度日本分類学会シンポジウム 2021年12月
• Visualizing statistical models via R-shiny  [招待講演]

  Isao Yokota

  DIA Japan annual meeting 2021 2021年10月 口頭発表（一般）
• 擬似値を用いたchance of a longer survivalの推定  [通常講演]

  横田 勲, 坂巻 顕太郎

  2021年度 統計関連学会連合大会 2021年09月 口頭発表（一般）
• 分子標的薬を用いた医師主導治験におけるバスケット試験デザインの利用  [招待講演]

  横田 勲, 髙木 諒, 岡田 和史

  第12回日本臨床試験学会学術集会 2021年02月 口頭発表（招待・特別）
• 陽性の頻度が稀な診断結果データに対するgold standardな検査法がない場合の感度・特異度推定  [通常講演]

  稲尾 翼, 岡田 和史, 楊 一馳, 横田 勲

  日本分類学会第39回大会 2020年11月
• Regression model for personalized chance of longer survival using pseudo-observations.

  Isao Yokota, Kentaro Sakamaki

  41st Annual Conference of the International Society of Clinical Biostatistics 2020年08月 口頭発表（一般）
• Using restricted mean survival time in a non-inferiority trial.  [通常講演]

  Isao Yokota, Yukari Uemura

  The VIth International Society for Biopharmaceutical Statistics 2019年08月 口頭発表（一般）
• 生存時間型アウトカムに対する単群試験のデザイン  [通常講演]

  横田 勲

  第60回日本小児血液・がん学会学術集会 2018年11月 口頭発表（招待・特別）
• 臨床研究における統計解析のポイント  [招待講演]

  横田 勲

  第33回日本環境感染学会総会・学術集会 2018年02月 口頭発表（招待・特別）
• United milestones survival analysis in single-arm trial  [招待講演]

  横田 勲

  2nd Paci fic Rim Cancer Biostatistics Workshop 2017年10月 口頭発表（招待・特別）
• 中間解析、中間モニタリングに用いられる統計手法  [通常講演]

  横田 勲

  ARO協議会 第5回学術集会 2017年09月 口頭発表（招待・特別）
• United milestones survival analysis in single-arm trial  [通常講演]

  横田 勲, 手良向 聡

  38th Annual Conference of the International Society for Clinical Biostatistics 2017年07月 ポスター発表
• Comparing the tests for a survival curve at a fixed time point in single arm study.  [通常講演]

  横田 勲

  ENAR 2017 Spring meeting 2017年03月 ポスター発表
• Comparison of sequential clinical trial designs with time-to-event outcomes in small populations  [通常講演]

  横田 勲, 柏原 康佑, 坂巻 顕太郎, 手良向 聡

  XXVIIIth International Biometric Conference 2016年07月 ポスター発表
• Dynamic prediction for repeated events data based on landmark model using dynamic pseudo observations  [通常講演]

  横田 勲, 松山 裕

  36th Annual Conference of the International Society for Clinical Biostatistics 2015年08月 口頭発表（一般）
• 動的予測を用いた代替エンドポイントの評価  [通常講演]

  横田 勲, 松山 裕

  2015年度 日本計量生物学会年会 2015年03月 ポスター発表
• Extension on a landmarking model using a fractional polynomial function for dynamic prediction  [通常講演]

  横田 勲, 松山 裕, 大橋 靖雄

  34th Annual Conference of the International Society for Clinical Biostatistics 2013年08月 ポスター発表
• Comparison of the tests for interval-censored data with differential assessment times  [通常講演]

  横田 勲, 松山 裕, 大橋 靖雄

  XXVIth International Biometric Conference 2012年08月 ポスター発表
• Simulation studies on the analysis of interval-censored survival data with differential assessment times  [通常講演]

  横田 勲, 松山 裕, 大橋 靖雄

  2012 Joint Statistical Meetings 2012年07月 ポスター発表

その他活動・業績

• 手指原発の悪性骨腫瘍における特徴 米国SEERデータベースを用いた研究

  池 翔太, 松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 菱村 亮介, 近藤 英司, 岩崎 倫政 日本整形外科学会雑誌 96 (3) S609 -S609 2022年03月
• 四肢原発軟部肉腫症例における患肢温存術と切断術の比較 米国SEERデータベースを用いた研究

  松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 菱村 亮介, 鈴木 裕貴, 岩田 玲, 近藤 英司, 岩崎 倫政 日本整形外科学会雑誌 96 (3) S1156 -S1156 2022年03月
• 初診時遠隔転移を有する椎体発生悪性骨腫瘍において原発巣切除は生存を改善するか 米国SEERデータベースを用いた研究

  松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 菱村 亮介, 鈴木 裕貴, 岩田 玲, 近藤 英司, 岩崎 倫政 日本整形外科学会雑誌 96 (3) S1157 -S1157 2022年03月
• 当院職員における新型コロナウイルスワクチン接種後の抗体価の検討

  大塚慎也, 大塚慎也, 平岡圭, 平岡圭, 鈴置真人, 氏家秀樹, 加藤達哉, 横田勲, 米澤一也, 小熊恵二, 岩代望, 加藤元嗣, 大原正範 北海道医学雑誌 97 (2) 2022年
• 生体腎移植ドナーの長期生命予後と腎機能推移の検討

  堀田 記世彦, 大澤 崇宏, 横田 勲, 稲尾 翼, 田邉 起, 岩原 直也, 篠原 信雄 日本泌尿器科学会総会 109回 OP56 -07 2021年12月
• CADASILでの塩酸ロメリジンを用いた脳梗塞発症抑制効果 最終報告

  渡邉 明子, 水田 依久子, 小泉 崇, 横田 勲, 向井 麻央, 濱野 愛, 近藤 正樹, 藤井 明弘, 松井 大, 松尾 宏俊, 伊藤 慶太, 手良向 聡, 山田 恵, 中川 正法, 水野 敏樹 臨床神経学 61 (Suppl.) S347 -S347 2021年09月
• 認知・生活機能質問票(DASC-8)を用いた目標HbA1cの達成に関連する患者背景因子の特定

  宮 愛香, 中村 昭伸, 横田 勲, 曹 圭龍, 亀田 啓, 野本 博司, 高瀬 崇宏, 大森 一乃, 永井 聡, 種田 紳二, 小野 真佑子, 渥美 達也, 三好 秀明 糖尿病合併症 35 (Suppl.) 172 -172 2021年09月
• CADASILでの塩酸ロメリジンを用いた脳梗塞発症抑制効果 最終報告

  渡邉 明子, 水田 依久子, 小泉 崇, 横田 勲, 向井 麻央, 濱野 愛, 近藤 正樹, 藤井 明弘, 松井 大, 松尾 宏俊, 伊藤 慶太, 手良向 聡, 山田 恵, 中川 正法, 水野 敏樹 臨床神経学 61 (Suppl.) S347 -S347 2021年09月
• 生体腎移植ドナーの腎機能と透析導入リスク 生体腎移植ドナーの長期生命予後と腎機能推移の検討

  堀田 記世彦, 大澤 崇宏, 横田 勲, 稲尾 翼, 田邉 起, 岩原 直也, 篠原 信雄 移植 56 (総会臨時) SSY2 -4 2021年09月
• 認知・生活機能質問票(DASC-8)を用いた目標HbA1cの達成に関連する患者背景因子の特定

  宮 愛香, 中村 昭伸, 横田 勲, 曹 圭龍, 亀田 啓, 野本 博司, 高瀬 崇宏, 大森 一乃, 永井 聡, 種田 紳二, 小野 真佑子, 渥美 達也, 三好 秀明 糖尿病合併症 35 (Suppl.) 172 -172 2021年09月
• 遠隔転移を有する四肢発生軟部肉腫症例において原発巣切除が生存に与える影響

  松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 松原 新史, 菱村 亮介, 近藤 英司, 岩崎 倫政 東日本整形災害外科学会雑誌 33 (3) 383 -383 2021年08月
• 軟部肉腫患者において初診時脳転移発生に寄与するリスク因子の探索 米国SEERデータベースを用いた研究

  糸賀 稜, 松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 松原 新史, 菱村 亮介, 近藤 英司, 岩崎 倫政 日本整形外科学会雑誌 95 (8) S1550 -S1550 2021年08月
• 手指原発の悪性骨腫瘍の検討

  池 翔太, 松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 菱村 亮介, 近藤 英司, 岩崎 倫政 日本整形外科学会雑誌 95 (8) S1557 -S1557 2021年08月
• 遠隔転移を有する四肢発生軟部肉腫症例において原発巣切除が生存に与える影響

  松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 松原 新史, 菱村 亮介, 近藤 英司, 岩崎 倫政 東日本整形災害外科学会雑誌 33 (3) 383 -383 2021年08月
• 軟部肉腫患者において初診時脳転移発生に寄与するリスク因子の探索 米国SEERデータベースを用いた研究

  糸賀 稜, 松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 松原 新史, 菱村 亮介, 近藤 英司, 岩崎 倫政 日本整形外科学会雑誌 95 (8) S1550 -S1550 2021年08月
• 手指原発の悪性骨腫瘍の検討

  池 翔太, 松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 菱村 亮介, 近藤 英司, 岩崎 倫政 日本整形外科学会雑誌 95 (8) S1557 -S1557 2021年08月
• 初診時遠隔転移を有する四肢発生軟部肉腫症例における原発巣切除の意義 米国SEERデータベースを用いた研究

  松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 松原 新史, 菱村 亮介, 近藤 英司, 岩崎 倫政 日本整形外科学会雑誌 95 (6) S1266 -S1266 2021年06月
• 軟部肉腫患者において初診時脳転移発生に寄与するリスクファクターの検討 米国SEERデータベースを用いた研究

  糸賀 稜, 松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 松原 新史, 菱村 亮介, 近藤 英司, 岩崎 倫政 日本整形外科学会雑誌 95 (6) S1314 -S1314 2021年06月
• 遠隔転移を有する脊椎発生悪性骨腫瘍において原発巣切除は生存を改善するか

  松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 菱村 亮介, 岩田 玲, 近藤 英司, 岩崎 倫政 日本整形外科学会雑誌 95 (6) S1348 -S1348 2021年06月
• 四肢原発骨・軟部肉腫症例における患肢温存術と切断術の比較 米国SEERデータベースを用いた研究

  中條 誠也, 松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 菱村 亮介, 近藤 英司, 岩崎 倫政 日本整形外科学会雑誌 95 (6) S1359 -S1359 2021年06月
• 手指原発の悪性骨腫瘍の特徴 米国SEERデータベースを用いた研究

  池 翔太, 松岡 正剛, 小野寺 智洋, 横田 勲, 岩崎 浩司, 菱村 亮介, 近藤 英司, 岩崎 倫政 日本整形外科学会雑誌 95 (6) S1396 -S1396 2021年06月
• 神経芽腫低リスクプロトコール(JN-L-10)におけるIDRFの検討

  米田 光宏, 家原 知子, 菱木 知郎, 横田 勲, 高橋 秀人, 手良向 聡, 上條 岳彦, 中澤 温子, 瀧本 哲也, 柳生 茂希, 池田 均, 菊田 敦, 中川原 章, 田尻 達郎, 日本小児がん研究グループ神経芽腫委員会 日本小児外科学会雑誌 57 (2) 301 -301 2021年04月
• 神経芽腫低リスクプロトコール(JN-L-10)におけるIDRFの検討

  米田 光宏, 家原 知子, 菱木 知郎, 横田 勲, 高橋 秀人, 手良向 聡, 上條 岳彦, 中澤 温子, 瀧本 哲也, 柳生 茂希, 池田 均, 菊田 敦, 中川原 章, 田尻 達郎, 日本小児がん研究グループ神経芽腫委員会 日本小児外科学会雑誌 57 (2) 301 -301 2021年04月
• 尿量の経日変化および前立腺体積が放射線治療時の前立腺の位置に与える影響(The Impact of Daily Urinary Volume Variations and Prostate Volume on Prostate Position During Radiotherapy)

  Nishioka Kentaro, Hashimoto Takayuki, Yokota Isao, Katoh Norio, Kinoshita Rumiko, Yasuda Koichi, Takao Seishin, Yoshimura Takaaki, Aoyama Hidefumi, Shimizu Shinichi 日本医学放射線学会学術集会抄録集 80回 S193 -S194 2021年03月
• The Impact of Daily Urinary Volume Variations and Prostate Volume on Prostate Position During Radiotherapy(和訳中)

  Nishioka Kentaro, Hashimoto Takayuki, Yokota Isao, Katoh Norio, Kinoshita Rumiko, Yasuda Koichi, Takao Seishin, Yoshimura Takaaki, Aoyama Hidefumi, Shimizu Shinichi 日本医学放射線学会学術集会抄録集 80回 S193 -S194 2021年03月
• 我が国における横紋筋肉腫治療多施設共同研究の歴史と今後の展望

  細井 創, 宮地 充, 土屋 邦彦, 細野 亜古, 小川 淳, 菊田 敦, 木下 義晶, 野澤 久美子, 藤 浩, 滝田 順子, 大喜多 肇, 長 祐子, 清谷 知賀子, 横田 勲, 瀧本 哲也, 手良向 聡, 日本小児がん研究グループ横紋筋肉腫委員会 日本小児科学会雑誌 125 (2) 191 -191 2021年02月 [査読有り]
  
• 小児の保健・医療のエビデンスを構築する前向き研究 希少疾患 横紋筋肉腫に対する臨床研究

  土屋 邦彦, 宮地 充, 細野 亜古, 小川 淳, 菊田 敦, 木下 義晶, 野澤 久美子, 藤 浩, 滝田 順子, 大喜多 肇, 長 裕子, 清谷 知賀子, 横田 勲, 瀧本 哲也, 手良向 聡, 細井 創, 日本小児がん研究グループ横紋筋肉腫委員会 日本小児科学会雑誌 125 (2) 164 -164 2021年02月
• 遠隔画像診断システムを用いた横紋筋肉腫委員会コンサルテーションチームの活動

  木下 義晶, 野澤 久美子, 藤 浩, 宮地 充, 土屋 邦彦, 細野 亜古, 小川 淳, 菊田 敦, 滝田 順子, 大喜多 肇, 長 祐子, 清谷 千賀子, 横田 勲, 瀧本 哲也, 手良向 聡, 細井 創, 日本小児がん研究グループ横紋筋肉腫委員会 日本小児科学会雑誌 125 (2) 192 -192 2021年02月
• 小児の保健・医療のエビデンスを構築する前向き研究 希少疾患 横紋筋肉腫に対する臨床研究

  土屋 邦彦, 宮地 充, 細野 亜古, 小川 淳, 菊田 敦, 木下 義晶, 野澤 久美子, 藤 浩, 滝田 順子, 大喜多 肇, 長 裕子, 清谷 知賀子, 横田 勲, 瀧本 哲也, 手良向 聡, 細井 創, 日本小児がん研究グループ横紋筋肉腫委員会 日本小児科学会雑誌 125 (2) 164 -164 2021年02月
• 我が国における横紋筋肉腫治療多施設共同研究の歴史と今後の展望

  細井 創, 宮地 充, 土屋 邦彦, 細野 亜古, 小川 淳, 菊田 敦, 木下 義晶, 野澤 久美子, 藤 浩, 滝田 順子, 大喜多 肇, 長 祐子, 清谷 知賀子, 横田 勲, 瀧本 哲也, 手良向 聡, 日本小児がん研究グループ横紋筋肉腫委員会 日本小児科学会雑誌 125 (2) 191 -191 2021年02月
• 遠隔画像診断システムを用いた横紋筋肉腫委員会コンサルテーションチームの活動

  木下 義晶, 野澤 久美子, 藤 浩, 宮地 充, 土屋 邦彦, 細野 亜古, 小川 淳, 菊田 敦, 滝田 順子, 大喜多 肇, 長 祐子, 清谷 千賀子, 横田 勲, 瀧本 哲也, 手良向 聡, 細井 創, 日本小児がん研究グループ横紋筋肉腫委員会 日本小児科学会雑誌 125 (2) 192 -192 2021年02月
• 終末期がん患者の予後ががん治療医の予後予測よりも短い要因について

  大場 洋子, 田中 輝明, 佐藤 雅子, 横田 勲, 瀧川 千鶴子 Palliative Care Research 16 (4) 307 -314 2021年 

  【目的】終末期がん患者の生存期間ががん治療医の経験に基づく予後予測よりも短い患者側の要因,および死亡までの経過との関連を検討する.【方法】KKR札幌医療センター緩和ケア病棟に予後1〜3ヵ月として紹介され,その後3ヵ月以内に死亡退院した終末期がん患者を対象に,後方視的検討を行った.【結果】対象患者249例のうち,実際の生存期間が1ヵ月未満であった患者は102例(OS1,41%),1ヵ月以上3ヵ月以内の患者は147例(OS1-3,59%)であった.Japan Coma Scale II以上の意識障害,経口摂取量数口以下を呈する患者がOS1-3に比べOS1で有意に多かった.2日以内で死に至る急な容態変化による死亡はOS1で有意に多かった.【結論】上記要因を持つ患者の生存期間は予測予後より短い可能性があるが,予後の不正確性に与える医師側の要因を検討する必要がある.(著者抄録)
• 分子標的薬を用いた医師主導治験におけるバスケット試験デザインの利用

  横田勲, 岡田和史, 高木諒 薬理と治療 49 (Suppl.1) s12 -15 2021年 [査読無し][招待有り]
  
• SOS/VOD評価における超音波検査スコアHokUS-3の検者再現性に関する検討

  岩井 孝仁, 西田 睦, 工藤 悠輔, 高杉 莉佳, 横田 勲, 高木 諒, 渋谷 斉, 高橋 秀一郎, 杉田 純一, 豊嶋 崇徳 超音波医学 47 (Suppl.) S344 -S344 2020年11月
• Oxaliplatinによる類洞閉塞症候群の診断における腹部超音波検査の有用性の検討

  斎藤 里佳, 西田 睦, 岩井 孝仁, 菊池 穏香, 吉野 裕紀, 横田 勲, 高木 諒, 川本 泰之, 山村 貴洋, 伊藤 憲, 中野 真太郎, 原田 一顕, 結城 敏志, 小松 嘉人, 坂本 直哉 日本癌治療学会学術集会抄録集 58回 P -178 2020年10月
• イベント予測モデルの評価指標

  篠崎 智大, 横田 勲, 大庭 幸治, 上妻 佳代子, 坂巻 顕太郎 計量生物学 41 (1) 1 -35 2020年10月 [査読有り][通常論文]
   

  Prediction models are usually developed through model-construction and validation. Especially for binary or time-to-event outcomes, the risk prediction models should be evaluated through several aspects of the accuracy of prediction. With unified algebraic notation, we present such evaluation measures for model validation from five statistical viewpoints that are frequently reported in medical literature: 1) Brier score for prediction error; 2) sensitivity, specificity, and C-index for discrimination; 3) calibration-in-the-large, calibration slope, and Hosmer-Lemeshow statistic for calibration; 4) net reclassification and integrated discrimination improvement indexes for reclassification; and 5) net benefit for clinical usefulness. Graphical representation such as a receiver operating characteristic curve, a calibration plot, or a decision curve helps researchers interpret these evaluation measures. The interrelationship between them is discussed, and their definitions and estimators are extended to time-to-event data suffering from outcome-censoring. We illustrate their calculation through example datasets with the SAS codes provided in the web appendix.
• 軟部肉腫において喫煙歴は肺転移発生の危険因子である

  松岡 正剛, 相馬 有, 新井 隆太, 横田 勲, 小野寺 智洋, 近藤 英司, 岩崎 倫政, 平賀 博明 日本整形外科学会雑誌 94 (3) S576 -S576 2020年03月
• 小児がん臨床研究の統計的デザイン 生存時間型アウトカムに対する単群試験のデザイン

  横田 勲 日本小児血液・がん学会雑誌 56 (5) 429 -431 2020年02月 [査読無し][招待有り]
   

  小児がん分野では、新規治療戦略の有効性を評価するため、イベント発生までの期間をエンドポイントとした単群試験がしばしば計画される。ヒストリカルコントロールから設定した閾値を用いて試験を計画する際に、パラメトリック法とマイルストン法が代表的なデザインとなる。ヒストリカルコントロールが存在しない場合のように予後を記載することが目的であるならば、精度ベースのサンプルサイズ設計を伴うデザインが採用される。本稿ではこれら試験デザインの特徴やサンプルサイズ設計に必要な情報、試験結果の解釈について解説する。(著者抄録)
• 北海道内の二次医療圏単位にみた大腸癌罹患に関する地域相関研究

  高橋祥, 高橋祥, 横田勲, 玉腰暁子 日本消化器がん検診学会雑誌(Web) 58 (Supplement 2) 2020年
• CADASILにおける塩酸ロメリジンの脳梗塞発症抑制効果の検討

  渡邉 明子, 水田 依久子, 濱野 愛, 小泉 崇, 松浦 潤, 向井 麻央, 横田 勲, 手良向 聡, 水野 敏樹 臨床神経学 59 (Suppl.) S327 -S327 2019年11月
• CADASILにおける塩酸ロメリジンの脳梗塞発症抑制効果の検討

  渡邉 明子, 水田 依久子, 濱野 愛, 小泉 崇, 松浦 潤, 向井 麻央, 横田 勲, 手良向 聡, 水野 敏樹 臨床神経学 59 (Suppl.) S327 -S327 2019年11月 [査読無し][通常論文]
  
• 前眼部3次元光干渉断層計による角膜前後面積比を用いた早期円錐角膜の診断

  糸井 素啓, 北澤 耕司, 横田 勲, 脇舛 耕一, 張 佑子, 中村 葉, 稗田 牧, 木下 茂, 外園 千恵 日本眼科学会雑誌 123 (臨増) 198 -198 2019年03月
• 前眼部所見からみた慢性期Stevens-Johnson症候群の悪化・非悪化に関する検討

  吉川 大和, 上田 真由美, 福岡 秀記, 田尻 健介, 稲富 勉, 横田 勲, 横井 則彦, 木下 茂, 池田 恒彦, 外園 千恵 日本眼科学会雑誌 123 (臨増) 202 -202 2019年03月
• 2動脈スティフネスに寄与しうる家庭血圧の脈圧閾値を解明する KAMOGAWA HBP cohort studyより2型糖尿病患者における検討

  北川 功幸, 牛込 恵美, 松本 しのぶ, 大藪 知香子, 横田 勲, 浅野 麻衣, 田中 武兵, 山崎 真裕, 福井 道明 日本内分泌学会雑誌 94 (4) 1585 -1585 2018年12月 [査読無し][通常論文]
  
• 脳血流測定によるCADASIL患者における脳梗塞発症予測の検討

  向井 麻央, 濱野 愛, 渡邉 明子, 小泉 崇, 松浦 潤, 水田 依久子, 横田 勲, 松島 成典, 手良向 聡, 山田 惠, 水野 敏樹 臨床神経学 58 (Suppl.) S339 -S339 2018年12月 [査読無し][通常論文]
  
• 肝癌研究会追跡調査よりみた高齢肝細胞癌に対する外科的切除の意義 Annals of Surgery

  海堀 昌樹, 吉井 健悟, 横田 勲, 長谷川 潔, 高山 忠利, 久保 正二, 權 雅憲, 泉 並木, 角谷 眞澄, 工藤 正俊, 熊田 卓, 坂元 亨宇, 中島 収, 松山 裕, 國土 典宏 日本外科学会定期学術集会抄録集 118回 773 -773 2018年04月
• 2動脈スティフネスに寄与しうる家庭血圧の脈圧閾値を解明する KAMOGAWA HBP cohort studyより2型糖尿病患者における検討

  北川 功幸, 牛込 恵美, 松本 しのぶ, 大藪 知香子, 横田 勲, 浅野 麻衣, 田中 武兵, 山崎 真裕, 福井 道明 日本内分泌学会雑誌 94 (1) 338 -338 2018年04月 [査読無し][通常論文]
  
• 動脈スティフネスに寄与しうる家庭血圧の脈圧閾値を解明する KAMOGAWA HBP cohort studyより2型糖尿病患者における検討

  北川 功幸, 牛込 恵美, 大藪 知香子, 松本 しのぶ, 横田 勲, 浅野 麻衣, 田中 武兵, 山崎 真裕, 福井 道明 糖尿病 61 (Suppl.1) S -272 2018年04月 [査読無し][通常論文]
  
• 研究と報告 高齢統合失調症患者を対象とした抗精神病薬と脂質異常症治療薬に関する医療同意能力の比較およびデシジョン・エイドによる介入の試み MacArthur Competence Assessment Tool for Treatmentを用いて

  加藤 佑佳, 松田 万祐理, 澤田 親男, 原田 倫治, 山田 美和, 加嶋 晶子, 柏 由紀子, 細井 哲, 横田 勲, 手良向 聡, 成本 迅 精神医学 60 (1) 75 -83 2018年01月 [査読無し][通常論文]
   

  単科精神科病院入院中の高齢統合失調症患者7名を対象に,抗精神病薬と脂質異常症治療薬の医療同意能力の異同を調べた結果,脂質異常症治療薬に比して抗精神病薬で「論理的思考」「結果の推測」の成績が有意に高かった。デシジョン・エイドの使用によって各医療同意能力レベルや医療同意能力のどの要素が改善するのかを検討したところ,抗精神病薬治療で「疾患の理解」「代替治療の理解」,脂質異常症治療薬では「理解」「治療の理解」「治療のメリットとデメリット」「代替治療の理解」「治療の認識」で,有意に成績が改善した。高齢統合失調症患者のワーキングメモリーの弱さを補うことが,医療同意能力における理解の改善に影響している可能性が考えられる。(著者抄録)
• 皮膚の視覚的パラメータを用いた死体の年齢推定

  坪井創, 横田勲, 高相真鈴, 高相真鈴, 池谷博 日本法科学技術学会誌 23 (Supplement) 2018年
• Re: Kitazawa et al.: Cystoid macular edema after Descemet's stripping automated endothelial keratoplasty (Ophthalmology. 2017; 124: 572-573) REPLY

  Koji Kitazawa, Kanae Kayukawa, Koichi Wakimasu, Isao Yokota, Tsutomu Inatomi, Osamu Hieda, Kazuhiko Mori, Chie Sotozono, Shigeru Kinoshita OPHTHALMOLOGY 124 (12) E86 -E87 2017年12月 [査読無し][通常論文]
  
• Interim Results of a Clinical Trial of IDRF for Intermediate-Risk Neuroblastoma from the Japan Neuroblastoma Study Group (JNBSG)

  T. Iehara, I. Yokota, A. Yoneda, T. Kamijo, A. Nakazawa, A. Kikuta, T. Takimoto, S. Teramukai, H. Hajime, A. Nakagawara, T. Tajiri PEDIATRIC BLOOD & CANCER 64 S229 -S230 2017年11月 [査読無し][通常論文]
  
• Surgical outcome of trabeculectomy with phakia, pseudophakia, and phaco trabeculectomy for open-angle glaucoma - Utilizing the data from the Collaborative Bleb-Related Infection Incidence and Treatment Study

  Yuji Yamamoto, Kazuhiko Mori, Isao Yokota, Kengo Yoshii, Yoko Ikeda, Morio Ueno, Kojiro Imai, Satoshi Teramukai, Shigeru Kinoshita, Chie Sotozono INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 58 (8) 2017年06月 

  0
• 病棟看護師の腰痛と労働生産性(プレゼンティーイズム)の関連性

  福谷 直人, 田中 真琴, 山中 寛恵, 任 和子, 横田 勲, 坂林 智美, 手良向 聡, 福本 貴彦, 青山 朋樹 産業衛生学雑誌 59 (臨増) 460 -460 2017年05月
• 病棟看護師の腰痛と労働生産性(プレゼンティーイズム)の関連性

  福谷 直人, 田中 真琴, 山中 寛恵, 任 和子, 横田 勲, 坂林 智美, 手良向 聡, 福本 貴彦, 青山 朋樹 産業衛生学雑誌 59 (臨増) 460 -460 2017年05月
• 再現性…相関係数とBland-Altman plot

  横田 勲 Coronary Intervention 13 47 -52 2017年05月 [査読無し][招待有り]
  
• A Comparison Between Cold Snare Polypectomy and Hot Snare Polypectomy for Resection Rate of Subcentimeter Colorectal Polyps: A Multicenter Randomized Controlled Trial (Crescent Study)

  Satoshi Asai, Takuji Kawamura, Yoji Takeuchi, Isao Yokota, Eisuke Akamine, Minoru Kato, Takuji Akamatsu, Kazuhiro Tada, Yoriaki Komeda, Mineo Iwatate, Ken Kawakami, Michiko Nishikawa, Daisuke Watanabe, Atsushi Yamauchi, Norimasa Fukata, Masaaki Shimatani, Makoto Ooi, Koichi Fujita, Yasushi Sano, Hiroshi Kashida, Satoru Hirose, Hiroyoshi Iwagami, Noriya Uedo, Satoshi Teramukai, Kiyohito Tanaka GASTROINTESTINAL ENDOSCOPY 85 (5) AB123 -AB123 2017年05月 [査読無し][通常論文]
  
• 白内障同時手術と濾過胞形状の関連性 濾過胞感染多施設共同研究データの検証

  山本 雄士, 森 和彦, 横田 勲, 吉井 健悟, 池田 陽子, 上野 盛夫, 今井 浩二郎, 手良向 聡, 木下 茂, 外園 千恵 日本眼科学会雑誌 121 (臨増) 243 -243 2017年03月 [査読無し][通常論文]
  
• NICUにおける沐浴時に洗浄剤を使わない皮膚洗浄法を検討する予備的研究 皮膚洗浄剤を使った場合との比較検討

  田仲 美沙, 甲良 里織, 岡田 ゆかり, 阪梨 真理子, 柳 茂香, 中島 輝美, 橋本 眞理子, 岩田 ちづる, 松岡 知子, 手良向 聡, 横田 勲, 山田 歩 京都府立医科大学附属病院看護部看護研究論文集 2015 17 -23 2017年02月 [査読無し][通常論文]
   

  早産児への適切な皮膚洗浄方法の検討に資するための予備的研究として、早産児7名を対象に、1日1回の沐浴について、皮膚洗浄剤を使用する介入群の後に皮膚洗浄剤を使用しないグループAと、非介入期の後に介入期を行うグループBのいずれかに割り付けるクロスオーバー試験を行った。その結果、いずれの群においても、沐浴と直接関係のある皮膚トラブルのような有害事象はみられなかった。
• 質の高い臨床研究実施計画書作成を志向する臨床研究教育ツール作成の試み

  松山 琴音, 須崎 友紀, 岩崎 幸司, 吉田 浩輔, 上村 尚人, 松嶋 由紀子, 長尾 典明, 小林 典子, 笠井 祥子, 横田 勲, 福間 真悟, 山本 学 臨床薬理 47 (Suppl.) S210 -S210 2016年10月
• 病棟看護師の腰痛が労働生産性(プレゼンティーイズム)に与える影響

  福谷 直人, 任 和子, 山中 寛恵, 手良向 聡, 横田 勲, 坂林 智美, 田中 真琴, 福本 貴彦, 坪山 直生, 青山 朋樹 理学療法学 43 (Suppl.2) O -1 2016年10月 [査読無し][通常論文]
  
• Does type of postoperative anti-glaucoma drug affect morphological changes of filtering bleb after trabeculectomy? - Utilizing the data from the Collaborative Bleb-Related Infection Incidence and Treatment Study

  Yuji Yamamoto, Kazuhiko Mori, Isao Yokota, Yoko Ikeda, Mario Ueno, Kojiro Imai, Haruna Yoshikawa, Satoshi Teramukai, Shigeru Kinoshita, Chie Sotozono INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE 57 (12) 2016年09月 [査読無し][通常論文]
  
• メタアナリシスのピットフォール

  横田 勲, 手良向 聡 循環器内科 79 (3) 267 -270 2016年03月 [査読無し][招待有り]
  
• 濾過胞形状と術後抗緑内障薬点眼薬の関連性 濾過胞感染多施設共同研究データの検証

  山本 雄士, 森 和彦, 横田 勲, 池田 陽子, 上野 盛夫, 今井 浩二郎, 吉川 晴菜, 手良向 聡, 木下 茂, 外園 千恵 日本眼科学会雑誌 120 (臨増) 270 -270 2016年03月 [査読無し][通常論文]
  
• A phase Ill trial of adjuvant capecitabine in breast cancer patients with HER2-negative pathologic residual invasive disease after neoadjuvant chemotherapy (CREATE-X, JBCRG-04)

  M. Toi, S-J Lee, E. S. Lee, S. Ohtani, Y-H Im, S-A Im, B-W Park, S-B Kim, Y. Yanagita, S. Takao, S. Ohno, K. Aogi, H. Iwata, A. Kim, H. Sasano, I. Yokota, Y. Ohashi, N. Masuda CANCER RESEARCH 76 2016年02月 [査読無し][通常論文]
  
• 病棟看護師の腰痛が労働生産性（プレゼンティーイズム）に与える影響

  福谷 直人, 任 和子, 山中 寛恵, 手良向 聡, 横田 勲, 坂林 智美, 田中 真琴, 福本 貴彦, 坪山 直生, 青山 朋樹 理学療法学Supplement 2015 1512 -1512 2016年 

  【はじめに，目的】腰痛は，業務上疾病の中で約6割を占める労働衛生上の重要課題であり，特に看護業界での課題意識は高い。近年では，仕事に出勤していても心身の健康上の問題で，労働生産性が低下するプレゼンティーイズムが着目されている。しかし，看護師の腰痛に着目し，急性/慢性腰痛とプレゼンティーイズムとの関連性を検討した研究はない。したがって，本研究では，看護師における急性/慢性腰痛がプレゼンティーイズムに与える影響を明らかにすることを目的とした。【方法】大学病院に勤務する看護師807名（平均年齢：33.2±9.6歳，女性91.0%）を対象に，自記式質問紙を配布し，基本属性（年齢，性別，キャリア年数），腰痛の有無，腰痛の程度（Numeric Rating Scale）を聴取した。腰痛は，現在の腰痛の有無と，現在腰痛がある場合，その継続期間を聴取することで，腰痛なし，急性腰痛（1日から3ヶ月未満），慢性腰痛（3ヶ月以上）に分類した。さらに，プレゼンティーイズムの評価としてWork Limitations Questionnaire-J（WLQ-J）を聴取した。WLQ-Jは，労働生産性を数値（%）で算出できる質問紙であり，"時間管理""身体活動""集中力・対人関係""仕事の結果"の下位尺度がある。統計解析では，対象者を腰痛なし群，急性腰痛群，慢性腰痛群に分類し，Kruskal Wallis検定（Bonferroni補正）およびカイ二乗検定にて基本属性，WLQ-Jを比較した。次に，従属変数に労働生産性総合評価および各下位尺度を，独立変数に急性腰痛の有無，または慢性腰痛の有無を，調整変数にキャリア年数・性別を投入した重回帰分析を各々行った（強制投入法）。統計学的有意水準は5%とした。【結果】回答データに欠測のない765名を解析対象とした。対象者のうち，363名（47.5%）が急性腰痛，131名（17.1%）が慢性腰痛を有していた。単変量解析の結果，腰痛なし群に比べ，急性および慢性腰痛群は有意に年齢が高く，キャリア年数も長い傾向が認められた（P＜0.001）。加えて，"労働生産性総合評価""身体活動""集中力・対人関係"において群間に有意差が認められた（P＜0.05）。重回帰分析の結果，急性腰痛が労働生産性に与える影響は認められなかったが，慢性腰痛は"集中力・対人関係"と有意に関連していた（非標準化β=-5.78，標準化β=-1.27，P=0.016，95%信頼区間-10.5--1.1）。【結論】本研究結果より，看護師の慢性腰痛は"集中力・対人関係"低下と有意に関連することが明らかとなった。急性腰痛は，発症してから日が浅いため，まだ労働生産性低下には関連していなかったと考えられる。しかし，慢性腰痛では，それに伴う痛みの増加や，うつ傾向などが複合的に"集中力・対人関係"を悪化させると考えられ，慢性腰痛を予防することで労働生産性を維持していくことの重要性が示唆された。
• The Kyoto Prognostic Index for patients with diffuse large B-cell lymphoma in the rituximab era

  T. Kobayashi, J. Kuroda, I. Yokota, K. Tanba, T. Fujino, S. Kuwahara, R. Isa, J. Yamaguchi, E. Kawata, T. Akaogi, H. Uchiyama, H. Kaneko, N. Uoshima, Y. Kobayashi, S. Teramukai, M. Taniwaki BLOOD CANCER JOURNAL 6 2016年01月 [査読無し][通常論文]
  
• 大学AROセンターにおける品質マネジメントシステム構築に対する取り組み

  松山 琴音, 今井 浩二郎, 横田 勲, 山田 歩, 手良向 聡, 中川 正法, 伏木 信次 臨床薬理 46 (Suppl.) S154 -S154 2015年11月 [査読無し][通常論文]
  
• CQARD設立による臨床研究質管理・保証への取り組み

  今井 浩二郎, 松山 琴音, 横田 勲, 山田 歩, 瀬戸山 晃一, 手良向 聡, 中川 正法, 伏木 信次 臨床薬理 46 (Suppl.) S255 -S255 2015年11月 [査読無し][通常論文]
  
• THE CORRELATION BETWEEN THE CHANGE OF DISTAL MOTOR LATENCY OF THE MEDIAN NERVE AND ABUNDANT A-WAVES IN GUILLAIN-BARRE SYNDROME

  Go Ogawa, Akiko Kadoya, Shingo Kawakami, Isao Yokota, Yuki Hatanaka, Ayumi Uchibori, Atsuro Chiba, Masahiro Sonoo MUSCLE & NERVE 52 S32 -S32 2015年10月 [査読無し][通常論文]
  
• 膵臓 切除不能膵がんへのアプローチ 膵癌に対するS-1通常投与法と隔日投与法のランダム化試験 安全性に関する報告

  石井 浩, 奥坂 拓志, 古瀬 純司, 大川 伸一, 福冨 晃, 井岡 達也, 庄 雅之, 柳本 泰明, 中森 正二, 北野 雅之, 馬場 秀夫, 清水 敦史, 横田 勲, 大橋 靖雄, 山上 裕機 日本癌治療学会誌 50 (3) 1402 -1402 2015年09月
• トラベクレクトミー術後眼圧と術前眼圧、濾過胞形状との関連性の検討

  山本 雄士, 森 和彦, 横田 勲, 池田 陽子, 上野 盛夫, 吉川 晴菜, 今井 浩二郎, 手良向 聡, 木下 茂 日本緑内障学会抄録集 26回 145 -145 2015年09月 [査読無し][通常論文]
  
• Interim safety analysis of a randomized phase II trial comparing alternate-day oral therapy using S-1 with the standard regimen as a first-line treatment for patients with advanced pancreatic cancer

  Hiroaki Yanagimoto, Takuji Okusaka, Hiroshi Ishii, Junji Furuse, Shinichi Ohkawa, Akira Fukutomi, Tatsuya Ioka, Masayuki Sho, Shoji Nakamori, Masayuki Kitano, Kazuya Sugimori, Hiroyuki Maguchi, Hiroshi Imaoka, Hideo Baba, Atsushi Shimizu, Isao Yokota, Yasuo Ohashi, Hiroki Yamaue JOURNAL OF CLINICAL ONCOLOGY 33 (15) 2015年05月 [査読無し][通常論文]
  
• Low body mass index (BMI) is associated with poor survival in Japanese patients with early breast cancer; an exploratory analysis of prospective randomized phase Ill trials N-SAS BC02 and 03

  Yoichi Naito, Yasuo Ohashi, Isao Yokota, Toru Watanabe, Hiroji Iwata, Shozo Ohsumi, Shinji Ohno, Yasuo Hozumi, Seiichiro Yamamoto, Masato Takahashi, Tomohiko Aihara, Hirofumi Mukai CANCER RESEARCH 75 2015年05月 [査読無し][通常論文]
  
• Impact of BMI on survival and toxicity in early breast cancer: An exploratory analysis of prospective randomized phase III study N-SAS BC02 and 03.

  Yoichi Naito, Yasuo Ohashi, Isao Yokota, Toru Watanabe, Hiroji Iwata, Shozo Ohsumi, Shinji Ohno, Yasuo Hozumi, Seiichiro Yamamoto, Masato Takahashi, Tomohiko Aihara, Hirofumi Mukai JOURNAL OF CLINICAL ONCOLOGY 33 (15) 2015年05月 [査読無し][通常論文]
  
• A randomized phase II study evaluating the use of prydoxine to prevent hand-foot syndrome associated with capecitabine therapy for advanced or metastatic breast cancer

  Akiyo Yoshimura, Hiroji Iwata, Takako Hayashi, Naomi Kobayashi, Kanako Saito, Michiko Tsuneizumi, Masataka Sawaki, Masaya Hattori, Takumi Nakada, Isao Yokota, Tatsuya Toyama JOURNAL OF CLINICAL ONCOLOGY 32 (15) 2014年05月 [査読無し][通常論文]
  
• Long-term follow-up data of the side effect profile of anastrozole compared with tamoxifen in Japanese women: findings from N-SAS BC03 trial.

  H. Iwata, S. Ohsumi, K. Aogi, Y. Hozumi, S. Imoto, H. Mukai, I. Yokota, T. Yamaguchi, Y. Ohashi, T. Watanabe, Y. Takatsuka, T. Aihara CANCER RESEARCH 72 2012年12月 [査読無し][通常論文]
  
• Superior efficacy of anastrozole to tamoxifen as adjuvant therapy for postmenopausal patients with hormone responsive breast cancer. Efficacy results of long-term follow-up data from N-SAS BC 03 trial

  S. Imoto, S. Osumi, K. Aogi, Y. Hozumi, H. Mukai, H. Iwata, I. Yokota, T. Yamaguchi, Y. Ohashi, T. Watanabe, Y. Takatsuka, T. Aihara CANCER RESEARCH 72 2012年12月 [査読無し][通常論文]
  

共同研究・競争的資金等の研究課題

• 多変量生存時間アウトカムに対する予測モデル構築と性能評価法の開発

  日本学術振興会：科学研究費助成事業 若手研究

  研究期間 : 2021年04月 -2025年03月 

  代表者 : 横田 勲

   

  初年度である令和3年度は、研究全体を遂行する上で最も重要となる、基盤的な理論構築に取り組んだ。また、一部の成果は国内学会で発表を通して、様々な研究者と議論することができ、次年度以降、さらに研究を発展させるための道筋を整理できた。 １）境界付き平均生存時間（RMST）の推定量を構成する上で基礎となる生存関数の情報量に関し、右側打ち切りの影響を有効サンプルサイズを尺度として評価できることを発見し、さらにその近似式を閉形式で表現できた。シミュレーション実験を通して、近似式の精度がよいことを確認した。RMST推定量の構成だけでなく、臨床試験デザインの開発におけるサンプルサイズ設計にも応用がきくことが分かり、重要な発見であると考えている。加えて、右側打ち切りだけではなく、区間打ち切りがみられる生存時間データへの応用も取り組み始めた。その途中経過を口頭発表を2021年日本分類学会シンポジウムにて行った。 ２）イベント確率予測モデルの判別指標をアウトカムと捉えたchance of longer survivalについて、回帰分析法を開発した。2021年度統計関連学会連合大会にて口頭発表を行った。回帰分析法は、pseudo-observationsの応用を通して方法論開発を行った。年度末には、このpseudo-observationsに関して先駆的な研究を実施している国外の研究者と次年度以降共同研究を開始する計画を立てた。加えて、予測に関する洋書の一部を翻訳した。これは、次年度以降出版を予定している。
• 法科学的体液資料を網羅する汎用性の高い体液の識別検査法の確立

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2021年04月 -2024年03月 

  代表者 : 阿久津 智子, 櫻田 宏一, 横田 勲

   

  月経血には、血液に加えて子宮内膜からの漏出液や剥離した組織片が含まれるため、データベースや文献検索により、子宮内膜に特徴的に発現する遺伝子を十数種選定し、月経血識別のためのマーカー候補とした。それらの月経血における検出性および他の体液への交差性を確認した結果、4遺伝子について、月経血での特異性が確認された。そこで、これらを月経血マーカーとし、フラグメント解析での検出のためのプライマーを設計し、月経血マルチプレックスRT-PCR系を構築した。標準的な各種体液試料における各マーカーの特異性を再度確認したところ、フラグメント解析により検出感度が向上したためか、一部の月経血マーカーで他の体液との交差性が認められたため、陽性判定のためのカットオフ値の設定あるいはそれぞれのマーカーの定量的評価が必要と考えられた。 鼻汁については、鼻粘膜での発現が解析されている遺伝子が限られているため、鼻粘膜に加え、気管あるいは肺に特徴的に発現する遺伝子を二十数種類選定し、鼻汁識別のためのマーカー候補とした。それらの鼻汁における検出性を確認したところ、いずれも、すでに16-plex RT-PCR系に組み込んでいるBPIFA1やSTATHと比較して、増幅が非常に弱いか認められなかった。プライマー濃度やPCR増幅条件あるいはプライマー配列を変更しても十分には改善しなかったため、今回選定した遺伝子を鼻汁マーカーとするのは難しいと考えられた。
• 左室駆出率が保持された心不全に対する個別化医療を目指した多分野融合研究

  日本学術振興会：科学研究費助成事業 基盤研究(B)

  研究期間 : 2020年04月 -2024年03月 

  代表者 : 安斉 俊久, 永井 利幸, 小川 貴弘, 横田 勲, 清水 厚志, 平田 健司, 小柴 生造, 櫻井 美佳

   

  HFpEF計500症例を目標に以下の組み入れ基準・除外基準で北海道大学病院を含む全国24施設からElectronic Data Captureシステムを用いて詳細な臨床情報を含めて登録し、各種解析を並行して実施した。組み入れ基準：外来もしくは入院心不全症例：①20歳以上でフラミンガム心不全診断基準を満足する心不全症状/所見があり、②左室駆出率50％以上かつBNP値100pg/mLを超えるもしくはN末端proBNP値400 pg/mLを超える、③本人からの文書同意が可能。除外基準：①敗血症、②心筋炎、③閉塞型肥大型心筋症、④拘束型心筋症、⑤重度の弁膜症、⑥心臓移植後あるいは待機、⑦1か月以内の予定心臓手術各種解析：①心不全マルチバイオマーカー解析 ②アレイ（ゲノムワイド関連）解析 ③網羅的メタボローム解析 ④人工知能解析 今年度は昨年度に引き続き、上記基準に該当する心不全症例の登録を開始してきた。令和4年3月末の時点で、目標症例数を超えるHFpEF664例の登録が得られ、バイオマーカー、アレイ、メタボローム解析も完了した。また、歩行動画の統一条件撮影に関しては昨年度特許申請に至った撮影アプリケーションを用いて現在歩行動画が回収できた192例に対し、歩行パターンの機械学習によるクラスター解析を行っており、教師なし学習で臨床医が判定した臨床フレイルスケールを高い弁別能で予測出来ることに加え、予後との関連も明らかになりつつある。
• SCRUM-Japanの基盤を活用した血液循環腫瘍DNAゲノムスクリーニングに基づくBRCA変異を有する胆道がんに対する医師主導治験

  国立研究開発法人日本医療研究開発機構：臨床研究・治験推進研究事業

  研究期間 : 2020年04月 -2024年03月 

  代表者 : 川本 泰之, 小松 嘉人, 畑中 豊, 畑中 佳奈子, 中村 能章, 谷口 浩也, 吉野 孝之, 森実 千種, 池田 公史, 上野 誠, 古川 正幸, 佐藤 太郎, 横田 勲, 磯江 敏幸
• 小児胎児性固形がんに対する標準的治療法開発

  国立研究開発法人日本医療研究開発機構：日本医療研究開発機構研究費

  研究期間 : 2020年04月 -2023年03月 

  代表者 : 檜山 英三, 田尻 達郎, 宮嵜 治, 吉村 健一, 横田 勲
• 小児およびAYA世代の横紋筋肉腫患者に対するリスク層別化臨床試験実施による標準的治療法の開発

  国立研究開発法人日本医療研究開発機構：

  研究期間 : 2020年04月 -2023年03月 

  代表者 : 細井 創, 小川 淳, 細野 亜古, 瀧本 哲也, 木下 義晶, 藤 浩, 宮嵜 治, 野澤 久美子, 小田 義直, 大喜多 肇, 櫻井 英幸, 川井 章, 横田 勲, 土屋 邦彦, 宮地 充
• 変異型新型コロナウイルスに対する診断・予防・治療法研究プラットフォームの開発

  国立研究開発法人日本医療研究開発機構：

  研究期間 : 2021年12月 -2022年03月 

  代表者 : 豊嶋 崇徳, 村上 正晃, 福原 崇介, 山岸 潤也, 高岡 晃教, 小園 晴生, 今野 哲, 横田 勲, 張替 秀郎, 藤井 聡, 高橋 聡, 鳥越 俊彦, 森石 恆司, 黒崎 知博, 谷口 正輝, 藤尾 圭志, 五十嵐 龍治
• マルチプレックスRT-PCR法による包括的な体液の識別検査法の開発

  日本学術振興会：科学研究費助成事業 基盤研究(C)

  研究期間 : 2018年04月 -2021年03月 

  代表者 : 阿久津 智子, 櫻田 宏一, 横田 勲

   

  まず、前研究課題の成果である、血液、唾液あるいは精液に対してそれぞれターゲット遺伝子3種およびリファレンス遺伝子1種を用いて構築したsingle body fluid（SB） Multiplex RT-PCR系について、フラグメントアナライザによる検出に向けてプライマー配列の一部を改変した。それらを用いて各体液試料を増幅し、プライマー配列の改変が非特異増幅、増幅バランス及び他の体液に対する交差性のいずれにも影響しないことを確認した。 つづいて、血液、唾液および精液に対するSB Multiplex RT-PCR系を統合し、複数種の体液に対するmulti-body fluids（MB）Multiplex RT-PCR系を構築した。MB Multiplex RT-PCR系における非特異増幅や増幅バランスの乱れについて、チップ電気泳動で確認したところ、プライマーダイマーが増加していたものの、非特異増幅は認められなかった。また、唾液に対するターゲット遺伝子の増幅が他の遺伝子と比較して低かったが、唾液中のRNA量が他の体液と比較して少ないことが原因と考えられたため、プライマー濃度の調整は行わないこととした。増幅サイズが近い一部のターゲット遺伝子は、チップ電気泳動法では分離できず、フラグメントアナライザでも分離困難となる可能性があるため、フラグメントアナライザによる検出に向けて、ターゲット遺伝子9種およびリファレンス遺伝子1種を数種の蛍光色素で標識することとした。
• 一類感染症等の患者発生時に備えた臨床的対応に関する研究

  厚生労働省：厚生労働行政推進調査事業費補助金

  研究期間 : 2020年06月 -2021年03月 

  代表者 : 豊嶋 崇徳, 横田 勲
• 食事評価・労働効率換算表を用いた身体障害者の労働生産性、就労支援創出の研究

  国立研究開発法人日本医療研究開発機構：障害者対策総合研究開発事業

  研究期間 : 2018年04月 -2021年03月 

  代表者 : 青山 朋樹, 横田 勲

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• 2023年03月 - 現在   日本計量生物学会   理事
• 2021年01月 - 現在   日本計量生物学会   社員（評議員）
• 2019年04月 - 現在   日本臨床腫瘍研究グループ   プロトコール審査委員
• 2018年06月 - 現在   International Biometric Society   Social Media Liaison
• 2016年10月 - 現在   日本計量生物学会   企画委員
• 2015年06月 - 現在   日本小児がん研究グループ   生物統計委員
• 2017年01月 - 2018年12月   日本計量生物学会   社員（評議員）