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Background: There are few reports on transthoracic echocardiography (TTE) for the evaluation of valvular heart disease in a specific area or region., Methods and Results: This cross-sectional questionnaire-based survey was conducted in 2023 in Kumamoto Prefecture, where 106 hospitals provide cardiology services. Ninety-three (88%) of the hospitals completed questionnaires regarding TTE. The severity of low flow/low gradient AS was evaluated by dobutamine stress echocardiography in only 7% of hospitals and exercise stress echocardiography for asymptomatic mitral regurgitation in only 5%. Multivariate logistic regression analysis revealed that participation in remote multi-institutional echocardiographic meetings and use of the Kumamoto Prefecture echocardiographic manual were significantly associated with the use of a multi-window approach (P < 0.05)., Conclusions: In Kumamoto Prefecture, echocardiographic measurements are performed according to the recommendations at a relatively low rate. Dissemination of recommendations through remote meetings and the use of the echocardiographic manual may increase the likelihood of TTE being performed according to the recommendations., Competing Interests: Declarations Conflict of interest H. U. received research grant from Pfizer Japan Incorporated and Edwards Lifesciences. Ethical approval The study protocol was approved by the Institutional Review Board of Kumamoto University (Kumamoto University Reference no. 1540) and conducted in accordance with the principles of the Declaration of Helsinki., (© 2024. Japanese Society of Echocardiography.)

Background: Patients with heart failure exhibiting low systolic blood pressure (SBP) have a poor prognosis. Sacubitril/valsartan reduces cardiovascular events; however, its use in patients with low SBP has not been fully examined. Therefore, in this study, we aimed to investigate the association between baseline SBP and adverse events (AEs) in patients starting sacubitril/valsartan therapy using data from a real-world registry in Japan., Methods: We analysed data from a multicentre retrospective study, including patients who initiated sacubitril/valsartan between August 2020 and August 2021. The patients were categorised into five groups based on their baseline SBP (<100, 100-109, 110-119, 120-129 and ≥130 mm Hg). The composite of AEs occurring within 3 months according to baseline SBP and the patient characteristics associated with AEs in a baseline SBP <110 mm Hg were analysed., Results: Among the 964 patients newly prescribed sacubitril/valsartan, the median (IQR) age was 73 (61-80) years, and 388 (40.2%) patients had a baseline SBP <110 mm Hg. AEs occurred in 24% (n=232) of patients. The adjusted ORs for all AEs were 1.91 (95% CI (CI) 1.13-3.23; p=0.02) for the SBP <100 mm Hg group and 3.33 (95% CI 1.98 to 5.59; p<0.001) for the SBP 100-109 mm Hg group, compared with the SBP 110-119 mm Hg group. In patients with a baseline SBP <110 mm Hg, factors associated with an increased risk of AEs included a higher New York Heart Association class (II, III or IV) and a lower estimated glomerular filtration rate <30 mL/min/1.73 m 2 ., Conclusions: Caution is needed when initiating sacubitril/valsartan in patients with lower baseline SBP. The severity of heart failure and kidney function may be useful for risk stratification in these high-risk patients., Competing Interests: Competing interests: K Kanaoka received speaker honoraria from Eli Lilly Japan and Otsuka Pharmaceutical Co., Ltd. K Kida received honorariums from AstraZeneca, Ono Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Otsuka Pharmaceutical Co., Ltd. and Novartis Pharmaceuticals Co., Ltd. SM received research grants and personal fees from Abbott, Bayer Pharma, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, Novartis, Ono Pharma, Orbus Neich, Otsuka Pharma and the Uehara Memorial Foundation., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Second primary esophageal cancer often develops in patients with head and neck cancer, and esophagectomy in patients with a history of total pharyngolaryngectomy (TPL) is challenging. However, the clinical outcomes of these patients have yet to be examined in a multicenter setting., Methods: We evaluated the surgical outcomes of a nationwide cohort of 62 patients who underwent esophagectomy for esophageal cancer with a history of TPL., Results: Ivor-Lewis and McKeown esophagectomies were performed in 32 (51.6%) and 30 (48.4%) patients, respectively. Postoperatively, 23 patients (37.1%) developed severe complications, and 7 patients (11.3%) required reoperation within 30 days. Pneumonia and anastomotic leakage occurred in 13 (21.0%) and 16 (25.8%) patients, respectively. Anastomotic leakage occurred more frequently in the McKeown group than in the Ivor-Lewis group (46.7% vs. 6.2%, P < 0.001). The adjusted odds ratio for anastomotic leakage in the McKeown group was 9.64 (95% confidence intervals (CI), 2.11-70.82, P = 0.008). Meanwhile, the 5-year overall survival rates were comparable between the groups (41.8% for Ivor-Lewis and 42.7% for McKeown), and the adjusted hazard ratio of overall survival was 1.44 (95% CI, 0.64-3.29; P = 0.381; Ivor-Lewis as the reference)., Conclusions: In our cohort, anastomotic leakage occurred more frequently after McKeown than Ivor-Lewis esophagectomy, and almost half of patients in the McKeown group experienced leakage. Ivor-Lewis esophagectomy is preferred for decreasing anastomotic leakage when oncologically and technically feasible., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Aim: The importance of comprehensive geriatric assessment (CGA) is increasing in aging societies worldwide. However, there are few comprehensive studies on CGA, resulting in a limited understanding of its implementation rate, temporal changes and factors associated with its implementation. We aimed to investigate the implementation status of CGA and its regional variance in Japan., Methods: Using the Diagnosis Procedure Combination database, we investigated CGA trends, and identified the patient, hospital and regional factors associated with its implementation. We identified patients aged ≥65 years who were admitted for the first time between 2016 and 2020 with a diagnosis of stroke, heart failure, pneumonia, bone fracture or colorectal cancer. We examined the CGA implementation rate according to patient and hospital characteristics. We also investigated temporal changes and tendencies to carry out CGA in different prefectures., Results: A total of 1 974 817 patients were analyzed, of whom 570 696 (28.9%) underwent CGA. The implementation trend increased steadily from 25.3% in fiscal year 2016 to 33.4% in fiscal year 2019. The implementation rate also increased with patient age (30.3% in patients aged ≥95 years). Regional variations in its implementation status were observed, with a higher tendency to be implemented in areas near major metropolitan regions. A trend toward carrying out CGA for colorectal cancer, but not for other diseases, has been observed in eastern Japan., Conclusion: Although CGA is increasingly carried out, considerable regional differences remain in its implementation status. Initiatives to reduce variations are necessary. Geriatr Gerontol Int 2024; 24: 904-911., (© 2024 The Author(s). Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Background: MET exon 14 skipping mutations occur in 3-4% and MET high amplifications occur in < 1% of patients with non-small-cell lung cancer (NSCLC). Crizotinib, a selective ATP-competitive small-molecule inhibitor of c-Met, ALK, and ROS1 tyrosine kinases, has shown activity in cancer models with various types of MET activation., Methods: The Co-MET study is a single-arm phase 2 trial to assess the safety and efficacy of crizotinib in MET inhibitor-naïve patients with advanced NSCLC harboring MET exon 14 skipping mutation (cohort 1) or high MET gene copy number of ≥ 7 (cohort 2). The primary endpoint was the objective response rate (ORR) per RECIST v1.1 by independent radiology review in cohort 1. The key secondary endpoints were the duration of response (DoR), progression-free survival (PFS), overall survival (OS), and safety., Results: A total of 28 patients (23 in cohort 1 and 5 in cohort 2) were enrolled between March 2018 and February 2020. The primary endpoint was met as the ORR (90% confidence interval: CI) in cohort 1 was 38.1% (20.6-58.3). Median DoR, PFS, and OS (95% CI) were 7.6 (1.9-NE), 5.7 (2.1-11.3), 9.1 (4.0-19.9) months, respectively, in cohort 1. ORR in cohort 2 was 40.0% (18.9-92.4). The safety signals were generally consistent with the known safety profile of crizotinib., Conclusions: Crizotinib showed a clinical activity similar to that of tepotinib and capmatinib in patients with NSCLC harboring MET exon 14 skipping mutations., Clinical Trial Information: UMIN000031623., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: The characteristics, tolerability, and outcomes in patients with heart failure (HF) who are treated with sacubitril/valsartan remain unclear in Japan., Methods: We conducted a nationwide multicenter study to evaluate the features and outcomes of patients newly prescribed sacubitril/valsartan for the management of HF. We analyzed adverse events (AEs) related to sacubitril/valsartan at 3 months, which were defined as hypotension, worsening renal function, hyperkalemia, and angioedema. Additionally, the association between AEs and outcomes was examined., Results: Among 993 patients, the mean age was 70 years and 291 (29.3 %) were female, and 22.8 % had left ventricular ejection fraction ≥50 %. Of them, 20.8 % had systolic blood pressure (sBP) <100 mmHg, and 19.5 % had estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m 2 at baseline, which were the populations excluded from the eligibility in landmark trials. AEs related to sacubitril/valsartan were observed in 22.5 % of the patients at 3 months. Overall, 22.6 % of patients discontinued sacubitril/valsartan, and hypotension was the most common event leading to drug discontinuation. After adjustment, patients who had worse HF symptoms (New York Heart Association III or IV), sBP <100 mmHg, and eGFR <30 ml/min/1.73 m 2 were associated with a higher risk of AEs related to sacubitril/valsartan. Additionally, patients experiencing AEs had a higher risk of cardiovascular death or HF hospitalization than those who did not., Conclusion: In Japan, sacubitril/valsartan was also prescribed to patients not eligible for landmark trials, and AEs were observed at a relatively high rate from soon after treatment initiation. Physicians should closely monitor patients for these events, especially in patients anticipated to have a higher risk of AEs., Competing Interests: Declaration of competing interest S.M. has received research grants and personal fees from Abott, Bayer Pharma, Boehringer Ingelheim, Daiichi-Sankyo, Medtronic, Novartis, Ono Pharma, Orbus Neich, Otsuka Pharma, and the Uehara Memorial Foundation. J.J.V.M. received payments through Glasgow University from work on clinical trials, consulting, and other activities from: Amgen, AstraZeneca, Bayer, Cardurion, Cytokinetics, GSK, KBP Biosciences, and Novartis. Personal consultancy fees from: Alnylam Pharma, Bayer, BMS, George Clinical PTY Ltd., Ionis Pharma., Novartis, Regeneron Pharma., River 2 Renal Corporation. Personal lecture fees: Abbott, Alkem Metabolics, Astra Zeneca, Blue Ocean Scientific Solutions Ltd., Boehringer Ingelheim, Canadian Medical and Surgical Knowledge, Emcure Pharma. Ltd., Eris Lifesciences, European Academy of CME, Hikma Pharmaceuticals, Imagica health, Intas Pharma, J.B. Chemicals & Pharma. Ltd., Lupin Pharma, Medscape/Heart.Org, ProAdWise Communications, Radcliffe Cardiology, Sun Pharma., The Corpus, Translation Research Group, and Translational Medicine Academy. J.J.V.M is a director of Global Clinical Trial Partners Ltd. J.J.V.M. is supported by a British Heart Foundation Centre of Research Excellence Grant RE/18/6/34217 and the Vera Melrose Heart Failure Research Fund. N.K. receives honorarium from Novartis Pharma, Boehringer-Ingelheim Japan, Eli Lilly Japan K.K, and Otsuka Pharma, and is affiliated with a department endowed by AMI Inc., Fukuda Denshi, KYOCERA, InterReha, and Philips Japan. T.S. has received honoraria from Novartis Pharmaceuticals KK, Boehringer Ingelheim, and Otsuka Pharmaceuticals Co. Ltd. A.K. has received honoraria from Novartis Pharma., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Aim: Patients with dementia with Lewy bodies (DLB) are at a high risk for falls and fractures. Although cholinesterase inhibitors reportedly are effective in suppressing the progression of cognitive symptoms in DLB patients, their effects on fracture risk remain unclarified. This study aimed to evaluate the association between donepezil use and hip fracture risk in older patients with DLB., Methods: Using the Japanese insurance claim database, we collected the data of patients aged ≥65 years with DLB from April 2012 to March 2019. After propensity score matching, we compared the fracture rate over 3 years between DLB patients receiving donepezil and those not receiving antidementia drugs., Results: Altogether, 24 022 239 individuals aged ≥65 years were newly registered from April 2012 to March 2016 and had verifiable information from 6 months before to 3 years after the registration. We identified 6634 pure-DLB patients and analyzed the data of 1182 propensity score-matched pairs. The characteristics, including age, sex, fracture history, osteoporosis, and bone mineral density test rate, of the two groups were well balanced by propensity score matching. The incidence rate of hip fracture was significantly lower in DLB patients receiving donepezil than in those not receiving antidementia drugs (0.60 vs. 1.44/100 person-years, P < 0.001), whereas that of vertebral fractures was the same., Conclusions: Donepezil administration in Japanese people aged ≥65 years with DLB was significantly associated with a decreased risk of hip fracture. Donepezil may provide new benefits to DLB patients. Geriatr Gerontol Int 2024; 24: 782-788., (© 2024 The Author(s). Geriatrics & Gerontology International published by John Wiley & Sons Australia, Ltd on behalf of Japan Geriatrics Society.)

Genetic factors, particularly human leukocyte antigen (HLA) class II genes, are known to significantly influence the onset of type 1 diabetes (T1D). Additionally, patients with T1D often develop autoimmune thyroid diseases (AITD). Despite this association, comprehensive research on individuals with both AITD and T1D in Japan, especially regarding the influence of specific HLA alleles, remains insufficient. In this retrospective study, we analyzed 44 inpatients diagnosed with T1D. These patients were predominantly female, with an average onset age of 35 years, poor blood sugar control, and approximately 43.2% had concurrent AITD. We observed significant associations of HLA-DRB1*04:05, HLA-DRB1*09:01 and HLA-DRB1*15:02 alleles with T1D regardless of AITD presence, which had been previously established for T1D in Japanese. In this context, comparing Japanese patients with AITD alone, we noted AITD comorbidity with T1D results in alterations in the frequencies of HLA-DRB1*09:01, HLA-DRB1*04:03, and HLA-DRB1*15:02. Furthermore, HLA-DRB1*04:05, HLA-DRB1*09:01, HLA-DRB1*13:02, and HLA-DRB1*15:01 alleles may be alleles whose susceptibility varies for both conditions. These findings underscore the importance of understanding the relationship between T1D, AITD, and HLA genetics, which may inform personalized treatment strategies and facilitate the development of targeted therapies. Future research endeavors should aim to elucidate underlying mechanisms and validate these findings in larger cohorts.

Background: There is a concern that the coronavirus disease 2019 (COVID-19) pandemic has led to underutilization of non-invasive positive pressure ventilation (NPPV) in patients with acute heart failure (HF). We investigated the alterations in clinical management of acute HF during the COVID-19 pandemic., Methods and Results: This study was an observational study of patients treated in emergency care with acute HF, using a Japanese Administrative database for a period before and during the COVID-19 pandemic. Of the 9081 overall eligible patients, the ratio of patients receiving NPPV and tracheal intubation during to before the COVID-19 pandemic were 0.88 [95 % confidence interval (CI): 0.80, 0.96] and 1.38 (95 % CI: 1.11, 1.71), respectively. Propensity score matching in patients treated in COVID-19 receiving facilities and emergency declaration response areas showed that ratio of NPPV and tracheal intubation during to before the COVID-19 pandemic were 0.88 (95 % CI: 0.76, 1.03), and 1.65 (95 % CI: 1.19, 2.28), respectively., Conclusions: The implementation rate of NPPV decreased significantly in eligible patients, with a decreasing trend observed in patient populations in COVID-19 receiving facilities and emergency declaration response areas. Tracheal intubation increased in all populations., Competing Interests: Declaration of competing interest Tatsuhiro Shibata has received honoraria from AstraZeneca KK, Daiichi Sankyo Co., Ltd., Novartis Pharmaceuticals KK, and Otsuka Pharmaceuticals Co., Ltd. Shingo Matsumoto received personal lecture fees from Abbott, Bayer Pharma, Boehringer Ingelheim, Medtronic, Novartis, Ono Pharma, OrbusNeich, and Otsuka Pharma. Tomoki Muramoto and Miyuki Matsukawa are employees of Otsuka Pharmaceutical Co., Ltd., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Managing complications in Type 1 diabetes (T1D) remains challenging. HLA genes, particularly DR and DQ, are linked to T1D susceptibility. We studied 48 Japanese T1D inpatients and revealed associations between DRB1*04:05-DQB1*04:01 and DRB1*09:01-DQB1*03:03 haplotypes and complications, offering a new perspective for future research., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: There is limited knowledge about early-onset dementia (EOD) on fracture risk., Methods: Individuals ages 50 to 64 were identified from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (2012 to 2019). The association between EOD and fractures and the association between cholinesterase inhibitors for EOD and fractures were evaluated using logistic regression analyses., Results: We identified 13,614 EOD patients and 9,144,560 cognitively healthy individuals. The analysis revealed that EOD was associated with an increased risk of hip fractures (adjusted odds ratio, 95% confidence interval: 8.79, 7.37-10.48), vertebral fractures (1.73, 1.48-2.01), and major osteoporotic fractures (2.05, 1.83-2.30) over 3 years. The use of cholinesterase inhibitors was significantly associated with a reduction in hip fractures among EOD patients (0.28, 0.11-0.69)., Discussion: EOD patients have a higher risk of osteoporotic fractures than cognitively healthy individuals. The use of cholinesterase inhibitors may reduce the risk of hip fracture among EOD patients., Highlights: It is unknown whether early-onset dementia (EOD) increases the risk of fractures. We identified 13,614 individuals with EOD using a nationwide administrative database. Patients with EOD have a higher risk of hip, vertebral, and major osteoporotic fractures. The use of cholinesterase inhibitors may reduce hip fracture among patients with EOD., (© 2024 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Familial hemophagocytic lymphohistiocytosis (FHLH) is a fatal hyperinflammation syndrome arising from the genetic defect of perforin-mediated cytolysis. Curative hematopoietic cell transplantation (HCT) is needed before development of central nervous system (CNS) disease. We studied treatment outcomes of 13 patients (FHLH2 n = 11, FHLH3 n = 2) consecutively diagnosed from 2011 to 2022 by flow cytometric screening for non-myeloablative HCT in a regional treatment network in Kyushu, Japan. One patient with a novel PRF1 variant escaped screening, but all patients with FHLH2 reached diagnosis and 8 of them received HCT until 3 and 9 months of age, respectively. The earliest HCT was conducted 65 days after birth. Three pretransplant deaths occurred in newborns with liver failure at diagnosis. Ten posttransplant patients have remained disease-free, 7 of whom had no neurological involvement. Time from first etoposide infusion to HCT was shorter in patients without CNS disease or bleeding than in patients with those factors (median [range] days: 62 [50-81] vs. 122 [89-209], p = 0.016). Six of 9 unrelated patients had a PRF1 c.1090&#95;1091delCT variant. These results suggest that the critical times to start etoposide and HCT are within 3 months after birth and during etoposide control, respectively. Newborn screening may increase the percentage of disease-free survivors without complications., (© 2024. Japanese Society of Hematology.)

This article reports the results of the 16th National Survey conducted by the Japan Society for Endoscopic Surgery (JSES) for 2020 and 2021. Laparoscopic cholecystectomy was first introduced to Japan in 1990 and has rapidly become popular because of its minimally invasive nature. Since then, the number of objective organs and indications for laparoscopic surgery have gradually expanded. In 2021, 290 787 patients underwent endoscopic surgery in all surgical domains. Of these, 124 614, 110 757, 23 156, 21 771, 6543, 2614, 535, 465, 247, and 58 underwent abdominal, obstetric and gynecologic, thoracic, urological, pediatric, orthopedic, bariatric, mammary and thyroid gland, cardiovascular, and plastic surgery, respectively. Owing to the impact of the coronavirus disease 2019 (COVID-19) infection spread, the incidence of many surgeries decreased in 2020, and levels are only now gradually recovering. However, despite the impact of COVID-19, robot-assisted surgeries were increasingly applied. The rate of complications did not change significantly, indicating that the procedure was performed safely, even with the spread of COVID-19., (© 2024 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Tepotinib is a highly selective MET tyrosine kinase inhibitor (TKI) that has demonstrated robust and durable clinical activity in patients with MET exon 14 (METex14) skipping non-small-cell lung cancer (NSCLC). In the Phase II VISION study, patients received oral tepotinib 500 mg once daily. The primary endpoint was an objective response by an independent review committee (IRC) according to RECIST v1.1 criteria. The secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Here we report the analysis of the efficacy and safety of tepotinib in all Japanese patients with advanced METex14 skipping NSCLC from VISION (n = 38) with >18 months' follow-up. The median age of the Japanese patients was 73 years (range 63-88), 39.5% of patients were ≥75 years old, 68.4% were male, 55.3% had a history of smoking, 76.3% had adenocarcinoma, and 10.5% of patients had known brain metastases at baseline. Overall, the objective response rate (ORR) was 60.5% (95% confidence interval (CI): 43.4, 76.0) with a median DOR of 18.5 months (95% CI: 8.3, not estimable). ORR in treatment-naïve patients (n = 18) was 77.8% (95% CI: 52.4, 93.6), and in patients aged ≥75 years (n = 15), ORR was 73.3% (95% CI: 44.9, 92.2). The most common treatment-related adverse event (AE) with any grade was blood creatinine increase (65.8%), which resolved following tepotinib discontinuation. Other common treatment-related AEs were peripheral edema (60.5%), hypoalbuminemia (34.2%), diarrhea (28.9%), and nausea (15.8%). In summary, tepotinib demonstrated robust and durable clinical activity irrespective of age or therapy line, with a manageable safety profile in Japanese patients with METex14 skipping NSCLC enrolled in VISION., (© 2024 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Objectives: The aim of the article is to investigate the associations of disease duration and anti-cyclic citrullinated peptide antibody (ACPA) status with the effectiveness of abatacept in biologic-naïve patients with rheumatoid arthritis (RA)., Methods: We performed post hoc analyses of the Orencia® Registry in Geographically Assembled Multicenter Investigation (ORIGAMI) study of biologic-naïve RA patients aged ≥20 years with moderate disease activity who were prescribed abatacept. Changes in the Simplified Disease Activity Index (SDAI) and Japanese Health Assessment Questionnaire (J-HAQ) at 4, 24, and 52 weeks of treatment were analysed in patients divided according to ACPA serostatus (positive/negative), disease duration (<1/≥1 year), or both., Results: SDAI scores decreased from baseline in all groups. SDAI scores tended to decrease more in the ACPA-positive group and disease duration <1-year group than in the ACPA-negative group and disease duration ≥1-year group, respectively. In the disease duration <1-year group, SDAI tended to decrease more in the ACPA-positive group than in the ACPA-negative group. Disease duration was independently associated with the change in SDAI and SDAI remission at Week 52 in multivariable regression models., Conclusions: These results suggest that starting abatacept within 1 year of diagnosis was associated with greater effectiveness of abatacept in biologic-naïve patients with RA and moderate disease activity., (© Japan College of Rheumatology 2023. Published by Oxford University Press.)

Background: Patients with chronic pancreatitis (CP) often have severe and intractable abdominal pain, leading to decreased quality of life (QOL), inability to work or attend school, and increased health care costs due to repeated emergency room visits and hospitalizations., Methods: We evaluated the efficacy of total pancreatectomy and islet autotransplantation (TPIAT) in terms of pain control and QOL in CP patients treated at our center in Japan. To evaluate QOL, we used the Short-Form 36 Health Survey version 2 (SF-36v2 ® Standard, Japanese), European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), and Quality of Life Questionnaire-Pancreatic Modification (QLQ-PAN28)., Results: Between August 2016 and June 2019, we performed this procedure in 5 patients. All patients were followed up for 12 months and all transplanted islets were still functioning at the 1-year follow-up. The major adverse events were abdominal wall hemorrhage, intestinal obstruction, intra-abdominal abscess, and abdominal pain requiring hospitalization; no case had sequelae. No major complications were due to islet transplantation. Pain scores improved postoperatively in all patients. Three QOL item dimensions role-physical ( p  = 0.03125), general health perception ( p  = 0.03125) and vitality ( p  = 0.03125) in the SF-36 were significantly improved 12 months after TPIAT. Mean values of many other QOL items improved, though not significantly., Conclusion: The QOL improvement after TPIAT for CP suggests its effectiveness in the Japanese population.

Lobella sauteri was redescribed based on the lectotype and specimens obtained from the type locality Bugenji, Yokohama, Kanagawa, as the true identity of the luminous Collembola, Lobella sp. Lobella sauteri has morphological traits characteristic of the genus currently called Telobella. As L. sauteri is the type species of Lobella, the genus Telobella was synonymised with Lobella according to the principle of priority, and the genus Lobella was redefined to include both the species previously assigned to Telobella and those previously assigned to Lobella. A new species Lobella monstrum sp. nov. was described and new combinations were proposed for certain species in Lobellini. Light-emitting capacity was confirmed in L. sauteri and newly reported in Lobella yambaru comb. nov. Vitronura giselae and Vitronura kunigamiensis.

Understanding seasonal groundwater quality changes in temperate continental climate waste rock dumps (WRDs) is necessary for sustainable environmental risk prevention and legacy mine contamination management. Therefore, we conducted a field investigation of a WRD to determine the mechanisms controlling its groundwater quality dynamics. The research aimed to understand the impact of seasonal changes on heavy metals released from the WRD. Three monitoring wells were installed in the WRD to investigate the pH, electrical conductivity (EC), and groundwater level (GL). The mineral composition of the waste rock was determined. Groundwater and river water samples from the monitoring wells and rivers surrounding the WRD were collected for chemical analysis. The sphalerite and galena concentrated in the WRD were assumed to be the main sources of Zn, Pb, and Cd contamination. Summer rainfall was the dominant recharge source of river water, which rapidly infiltrated to the WRD, altering the pH, EC, and GL of the groundwater. The pH, EC, and GL were stable in winter because snowpack covering the surface soil prevented groundwater recharge to the WRD. However, snow melting affected the pH, EC, and GL in the WRD. The sources of groundwater recharge (rainfall, river water, and snowmelt) altered the behaviour of the heavy metals in the WRD through two main mechanisms: the dissolution of sulphide minerals and efflorescent salts upon contact with the recharge water, and the dilution effect of the recharge water, which mixes with the groundwater in the WRD, reducing the heavy metal concentration. Sulphide mineral and efflorescent salt dissolution were significant in the deepest monitoring well and rainfall was the dominant recharge source which increased sulphide mineral and efflorescent salt dissolution in the WRD., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

A qualitative assessment of groundwater resources is significant in islands that largely depend on individual aquifers. In Okinawa Island, Japan, limestone aquifers are valuable groundwater reservoirs. However, these aquifers are sensitive to contamination due to high permeability in the conduit network. Although human activity has increased in recent decades, there remains insufficient hydrological information to assess the impact of anthropogenic loading on groundwater quality in Okinawa Island. To address this, we analyzed 4 seepage, 16 river, and 14 shallow (<10 m in depth) groundwater samples to obtain baseline chemistry and anthropogenic impact information on groundwater resources in central Nago City, northern Okinawa Island. We divided the region into three landscape units: lowland (<30 m asl), eastern, and western areas. Except for a limited number of water samples collected in the eastern mountain and coastal section of the lowland, the hydrochemistry was characterized by Ca-HCO 3 type, indicating carbonate weathering within limestone-bearing lithology and Quaternary deposits. Divergent water 87 Sr/ 86 Sr values (0.707723-0.712102) with lower Sr concentrations (0.1-1.6 μmol/L) in the mountains and convergent values (0.708859-0.709184) with higher Sr concentrations (0.3-17.6 μmol/L) in the lowland suggest that the water-rock interactions in the lowland aquifer composed of Quaternary deposits are mostly responsible for the hydrochemistry of groundwater resources. The local meteoric water line (δD = 6.38 δ 18 O + 3.36) indicated that the water originates from precipitation, the altitude effect, and evaporation. The δ 15 N and δ 18 O in NO 3 - indicated the addition of manure and septic waste in the lowland aquifer. The results imply that detecting source areas of anthropogenic NO 3 - prior to serious groundwater pollution is important (regardless of the NO 3 - concentration), and isotope analyses would aid in developing appropriate action plans to mitigate or prevent future water pollution by NO 3 - in island regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: No studies have examined the associations between adult height and ischemic stroke subtypes., Methods: We conducted a population-based case-control study that included 2,451 thrombotic and 687 embolic stroke cases, as well as 1,623 intracerebral and 768 subarachnoid hemorrhage cases without history of stroke aged 40-79 years, and the same number of sex- and age-matched controls. Cases and controls were grouped according to the quintile cut-off values of height in controls, and the third quintile, which was approximately the average height group, was used as the reference group. Height divided by one standard deviation of height in controls was also examined as a continuous variable. The analyses were carried out separately for participants aged 40-59 years and 60-79 years., Results: In both younger and older men, height was linearly inversely associated with total and thrombotic strokes, and the shortest quintile compared to the reference group was associated with increased risks of these strokes. Although height was linearly inversely associated with embolic stroke and intracerebral hemorrhage in younger men, the shortest quintile did not show increased risks of these strokes. Height did not seem to be associated with total stroke and any stroke subtypes in younger women. In contrast, the tallest quintile was significantly associated with increased risks of total stroke and intracerebral hemorrhage, and height tended to be positively associated with these strokes in older women., Conclusion: We reported the associations between adult height and ischemic stroke subtypes for the first time, which differed according to sex and age group.

This real-world study examined the prevalence of programmed death ligand-1 (PD-L1) expression and assessed the frequency of microsatellite instability-high (MSI-H) status and Epstein-Barr virus (EBV) positivity in Japanese patients with advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma. This multicenter (5 sites), retrospective, observational study (November 2018-March 2019) evaluated Japanese patients with advanced gastric and GEJ adenocarcinoma after surgical resection (Stage II/III at initial diagnosis) or unresectable advanced cancer (Stage IV). The primary objectives were prevalence of PD-L1 expression (combined positive score [CPS] ≥1), MSI status, and EBV positivity. Tumor specimens of 389/391 patients were analyzed (male, 67.1%; mean age, 67.6 ± 12.2 years); 241/389 (62%) were PD-L1 positive, 24/379 (6.3%) had MSI-H tumors, and 13/389 (3.3%) were EBV positive. PD-L1 expression was higher in tumor-infiltrating immune cells than in tumor cells for lower CPS cutoffs. Among patients with MSI-H tumors and EBV-positive tumors, 19/24 (79.2%) and 9/13 (69.2%), respectively, were PD-L1 positive. A greater proportion of patients with MSI-H tumors (83.3% [20/24]) were PD-L1 positive than those with MSI-low/stable tumors (60.8% [216/355]; p = .0297); similarly, an association was observed between history of H pylori infection and PD-L1 expression. A higher proportion of patients with MSI-H tumors demonstrated PD-L1 expression with a CPS ≥10 (66.7% [16/24]) vs those with MSI-low/stable tumors (24.8% [88/355]; p < .0001). The prevalence of PD-L1 positivity among Japanese patients was comparable to that in previous pembrolizumab clinical trials and studies in gastric cancer. Particularly, higher PD-L1 expression was observed in MSI-H tumors.

Objectives: This study aims to determine whether there is a difference in the academic performance of medical students based on admission type and examine the extent to which entrance examinations predict their performance., Methods: This observational study utilized existing data from Asahikawa Medical University. Participants were 1057 medical students who had enrolled between 2010 and 2019. Analysis of variance and Tukey's test were utilized to identify differences between admission types. The multiple linear regression explored predictors of cumulative grade point average for each type., Results: Analysis of variance showed significant differences in the National Center Test (F (3, 1053) =70.78, p <0.001) and cumulative grade point average (F (3, 1053) =3.93, p <0.01). Tukey's post hoc test revealed that two types of general admission students (M=83.52, SD=3.22; M=85.57, SD=3.01) were significantly higher on the National Center Test than two types of regional quota students (M=81.61, SD=3.93; M=80.65, SD=3.61). The cumulative grade point average of a regional quota group (M=2.23, SD=0.34) was significantly higher than two types of general admissions (M=2.11, SD=0.36; M=2.12, SD=0.34). High school grade point averages and females were significant in predicting cumulative grade point averages for each admission (16.0-28.3% variance)., Conclusions: Regional quota students earned a higher cumulative grade point average than those from general admissions, despite their significantly lower scores on the National Center Test. Enhanced utilization of regional quota admissions could become an effective strategy to increase the rural physician workforce.

Cyclones can cause mass mortality of seabirds, sometimes wrecking thousands of individuals. The few studies to track pelagic seabirds during cyclones show they tend to circumnavigate the strongest winds. We tracked adult shearwaters in the Sea of Japan over 11 y and found that the response to cyclones varied according to the wind speed and direction. In strong winds, birds that were sandwiched between the storm and mainland Japan flew away from land and toward the eye of the storm, flying within ≤30 km of the eye and tracking it for up to 8 h. This exposed shearwaters to some of the highest wind speeds near the eye wall (≤21 m s -1 ) but enabled them to avoid strong onshore winds in the storm's wake. Extreme winds may therefore become a threat when an inability to compensate for drift could lead to forced landings and collisions. Birds may need to know where land is in order to avoid it. This provides additional selective pressure for a map sense and could explain why juvenile shearwaters, which lack a map sense, instead navigating using a compass heading, are susceptible to being wrecked. We suggest that the ability to respond to storms is influenced by both flight and navigational capacities. This may become increasingly pertinent due to changes in extreme weather patterns.

Objectives: This study examined the characteristics of occupational mental disorders among those involved in the transport and postal activities in the trucking industry., Method: We examined 237 out of 3,517 cases of occupational mental disorders, compensated between the fiscal years 2010 and 2017. An assessment was made for sex, "life-or-death" status at compensation, age at the onset and suicide, the diagnosis according to the International Classification of Diseases, Tenth Revision, and other factors regarding occupational compensation. The participants were divided into two groups: truck drivers and non-truck drivers., Results: Men accounted for approximately 90% of the cases. Depressive episode (F32) was the most common diagnosis in drivers and non-drivers, thus constituting 65 out of 149 and 48 out of 88 cases, respectively. The next most common type of mental disorder was adjustment disorders (F43.2), with 34 out of 149 drivers and 24 out of 88 non-drivers reporting them. Furthermore, the majority of drivers that had posttraumatic stress disorder (24 out of 27 cases) reported that they "suffered a serious illness or injury" and "experienced or witnessed a terrible accident or disaster." Occupational disasters due to long working hours were 52.4% for drivers and 73.9% for non-drivers. A total of 30.8% of the drivers reported working long hours since they joined the company., Conclusion: Drivers' long working hours entail waiting at the origin and cargo destination site, handling cargo, and incidental tasks other than driving. Thus, the reduction in work hours regarding these tasks needs to be a fundamental goal, and measures that include mental health care for accidents and miserable experiences must be implemented. However, long working hours for non-drivers are likely linked to job expansion/increase and reassignment/relocation. These findings highlight that to prevent overwork-related mental disorders, appropriate actions should be taken considering different sources of exposure for drivers or non-drivers.

Aims: This study evaluated the prognosis and prognostic factors of patients with cardiac sarcoidosis (CS), an underdiagnosed disease., Methods and Results: Patients from a retrospective multicentre registry, diagnosed with CS between 2001 and 2017 based on the 2016 Japanese Circulation Society or 2014 Heart Rhythm Society criteria, were included. The primary endpoint was a composite of all-cause death, hospitalization for heart failure, and documented fatal ventricular arrhythmia events (FVAE), each constituting exploratory endpoints. Among 512 registered patients, 148 combined events (56 heart failure hospitalizations, 99 documented FVAE, and 49 all-cause deaths) were observed during a median follow-up of 1042 (interquartile range: 518-1917) days. The 10-year estimated event rates for the primary endpoint, all-cause death, heart failure hospitalizations, and FVAE were 48.1, 18.0, 21.1, and 31.9%, respectively. On multivariable Cox regression, a history of ventricular tachycardia (VT) or fibrillation [hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.59-4.00, P < 0.001], log-transformed brain natriuretic peptide (BNP) levels (HR 1.28, 95% CI 1.07-1.53, P = 0.008), left ventricular ejection fraction (LVEF) (HR 0.94 per 5% increase, 95% CI 0.88-1.00, P = 0.046), and post-diagnosis radiofrequency ablation for VT (HR 2.65, 95% CI 1.02-6.86, P = 0.045) independently predicted the primary endpoint., Conclusion: Although mortality is relatively low in CS, adverse events are common, mainly due to FVAE. Patients with low LVEF, with high BNP levels, with VT/fibrillation history, and requiring ablation to treat VT are at high risk., Competing Interests: Conflict of interest: Y.M. received an honorarium from Otsuka Pharmaceutical Co. and Novartis Japan. Other authors have nothing to declare., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge 1-5 . Here we conducted a genome-wide association study (GWAS) involving 2,393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3,289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target., (© 2022. The Author(s).)

Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection., (© 2022. The Author(s).)

Objectives: To evaluate the effectiveness and safety of abatacept over 52 weeks in biologic-naïve rheumatoid arthritis (RA) patients with moderate disease activity in the prospective, 5-year, observational study (ORIGAMI study) in Japan., Methods: Abatacept (125 mg) was administered subcutaneously once a week. Clinical outcomes included Simplified Disease Activity Index (SDAI) remission at Week 52 (primary endpoint), Japanese Health Assessment Questionnaire (J-HAQ), EuroQol 5-Dimension Questionnaire (EQ-5D), treatment retention, and safety. The results were compared with those of conventional synthetic disease-modifying antirheumatic drug (csDMARD) controls from the ongoing Institute of Rheumatology, Rheumatoid Arthritis (IORRA) registry., Results: Overall, 325 patients were enrolled, with a mean age of 66.9 ± 12.7 years. The proportion of patients achieving SDAI remission (≤3.3) at Week 52 was 18.9% (95% CI: 14.3-23.6) and low disease activity (≤11) was 53.3% (95% CI: 47.4-59.1). A significant improvement was observed in J-HAQ and EQ-5D over 52 weeks in both the abatacept and csDMARD groups. The probability of abatacept treatment retention at Week 52 was 69.9% (95% CI: 64.7-75.5). Adverse events and serious adverse events were reported in 50.0% and 12.1% of patients, respectively., Conclusions: Abatacept significantly improved disease activity, physical disability, and quality of life for up to 52 weeks in RA patients in a real-world setting., (© Japan College of Rheumatology 2021. Published by Oxford University Press.)

Introduction: Patients with COVID-19 and cardiovascular disease risk factors (CVDRF) have been reported to develop coagulation abnormalities frequently. However, there are limitations in conventional predictive models for the occurrence of thromboembolism in patients with COVID-19 and CVDRF., Methods: Among data on 1518 hospitalized patients with COVID-19 registered with CLAVIS-COVID, a Japanese nationwide cohort study, 693 patients with CVDRF were subjected to least absolute shrinkage and selection operator (LASSO) analysis; a method of shrinking coefficients for reducing variance and minimizing bias to increase predictive accuracy. LASSO analysis was performed to identify risk factors for systemic thromboembolic events; occurrence of arterial and venous thromboembolism during the index hospitalization as the primary endpoint., Results: LASSO analysis identified a prior systemic thromboembolism, male sex, hypoxygenemia requiring invasive mechanical ventilation support, C-reactive protein levels and D-dimer levels at admission, and congestion on chest X-ray at admission as potential risk factors for the primary endpoint. The developed risk model consisting of these risk factors showed good discriminative performance (AUC-ROC: 0.83, 95 % confidence interval [CI]: 0.77-0.90), which was significantly better than that shown by D-dimer (AUC-ROC: 0.70, 95 % CI: 0.60-0.80) (p < 0.001). Furthermore, systemic embolic events were independently associated with in-hospital mortality (adjusted odds ratio: 3.29; 95 % CI: 1.31-8.00)., Conclusions: Six parameters readily available at the time of admission were identified as risk factors for thromboembolic events, and these may be capable of stratifying the risk of in-hospital thromboembolic events, which are associated with in-hospital mortality, in patients with COVID-19 and CVDRF., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

In the treatment of an intracranial aneurysm with the flow diverter, the combined use of coil embolization can help promote subsequent progressive thrombosis within the aneurysm sac and reduce the risk of delayed aneurysm rupture. This study retrospectively reviewed outcomes of patients who had undergone the Pipeline Embolization Device (PED) with adjunctive coil embolization (PED/coil) at a single center to determine its safety and efficiency. Patients with internal carotid artery aneurysms following an intradural component were selected for PED/coil between 2015 and 2020. All patients were premedicated with dual antiplatelet therapy of aspirin plus clopidogrel or prasugrel. A minimal number of PEDs were deployed, with coils inserted using a stent-jail technique, avoiding dense packing. A total of 46 aneurysms (43 patients; median dome size, 11.6 mm; median neck width, 6.3 mm) were treated with PED/coil. The median volume embolization ratio was 14.8%. The degree of angiographic filling at the 6-month and latest angiography showed complete occlusion in 60.5% (26/43) and 70.5% (31/44), respectively. Small (< 10 mm) aneurysms achieved a higher complete occlusion rate in the early period; a lower cumulative incidence of aneurysm occlusion was observed in large and giant (≥ 10 mm) aneurysms (P = .024). The median clinical follow-up was 22 months, and no aneurysm ruptures occurred. Favorable clinical outcomes were achieved, with permanent neurological morbidity of 4.7% and no mortality. PED/coil demonstrated a high angiographic occlusion rate at an early stage. Loosely packed coils are sufficient to obliterate aneurysms effectively., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Glasgow prognostic score (GPS) has been used to evaluate inflammatory response and nutritional status. This study aimed to investigate the impact of nutritional status on cardiac prognosis by using GPS in patients after undergoing percutaneous coronary intervention (PCI). We included 862 patients who underwent PCI for stable angina pectoris between 2015 and 2018. We used the original cutoff values, which were an albumin (Alb) level of 3.5 g/dl and a C-reactive protein (CRP) level of 0.3 mg/dl. We categorized them into the three groups: originally defined GPS (od-GPS) 0 (high Alb and low CRP), 1 (low Alb or high CRP), and 2 (low Alb and high CRP). Major adverse clinical events (MACEs) included all-cause death, nonfatal myocardial infarction, revascularization, and hospitalization for heart failure. The median follow-up period was 398.5 days. During the follow-up, MACEs occurred in 136 patients. Od-GPS 2 had higher prevalence rates in terms of chronic kidney disease (CKD; 31.7% [229/722] vs. 44.9% [53/118] vs. 63.6% [14/22], p < 0.001), hemodialysis (6.4% [46/722] vs. 14.4% [17/118] vs. 31.8% [7/22], p < 0.001), and heart failure cases (HF; 9.1% [66/722] vs. 14.4% [17/118] vs. 27.3% [6/22], p = 0.007), with higher creatinine (1.17 ± 1.37 mg/dl vs. 1.89 ± 2.60 mg/dl vs. 3.49 ± 4.01 mg/dl, p < 0.001) and brain natriuretic peptide levels (104.1 ± 304.6 pg/ml vs. 242.4 ± 565.9 pg/ml vs. 668.1 ± 872.2 pg/ml, p < 0.001) and lower low-density lipoprotein cholesterol (101.5 ± 32.9 mg/dl vs. 98.2 ± 28.8 mg/dl vs. 77.1 ± 24.3 mg/dl, p = 0.002) than od-GPS 0 and 1.Od-GPS 2 (HR 2.42; 95% CI 1.16-5.02; p = 0.018), od-GPS 1 (HR 2.09; 95% CI 1.40-3.13; p < 0.001), diabetes (HR 1.41; 95% CI 1.00-1.99; p = 0.048), CKD (HR 2.10; 95% CI 1.49-2.96; p < 0.001), and HF (HR 1.64; 95% CI 1.05-2.56; p = 0.029) were independent predictors of MACEs. A scoring system using CRP and Alb levels with a milder definition than GPS suitably predicted the risk of MACEs in the patients who underwent PCI., (© 2021. Springer Japan KK, part of Springer Nature.)

Research on mental health in working populations has predominantly focussed on negative outcomes, while studies on the positive aspects of life remain very limited, especially in Japan. Although morningness has recently been considered a factor for being happy, the role of sleep characteristics as it relates to the association between morningness and happiness has not been substantiated. The aim of this study is to investigate the associations between diurnal preference and level of subjective happiness in healthy, full-time, daytime workers in Japan. We also tested the moderation effect of sleep parameters on the relationship between diurnal preference and subjective happiness. This is an exploratory analysis from the cross-sectional data of the SLeep Epidemiology Project at the University of Tsukuba (SLEPT Study). Subjective happiness was evaluated using a single-item question. Diurnal preference was assessed using the Morningness-Eveningness Questionnaire (MEQ), in which higher scores indicate greater tendency to have morning preference. The participants underwent assessment of sleep parameters for 7 consecutive days using a waist-worn actigraphy device and kept a sleep diary. Sleep parameters investigated were subjective sleep quality, sleep disturbance, daytime sleepiness, weekend oversleep, total sleep time, sleep onset time, wake time, and sleep efficiency. A total of 205 males (average 42.6 ± 10.4 years) and 272 females (41.1 ± 9.8 years) were eligible for analysis. Hierarchical liner regression analysis was used to show the relationships of subjective happiness with MEQ score, and the sleep parameters. Further, moderation analysis was conducted by adding the interaction between MEQ score and the sleep parameters. After adjusting for age, psychological distress, self-rated health, and occupational stress, we found that subjective happiness was significantly associated with higher MEQ score and sleep efficiency but only in female. The moderating role of sleep parameters was not found. We discussed the implications of the obtained results and a possible strategy to maintain and improve subjective happiness of female workers who have evening preference.

Background: Previous studies have suggested an association between higher levels of parental autistic traits and negative aspects of parenting; however, the domain of autistic traits specifically associated with parenting difficulties has not been investigated yet. Moreover, it remains to be determined whether this association exists even after controlling for children's characteristics., Aims: This study examined the relationship between each domain of parental autistic traits and parenting difficulties after controlling for children's characteristics in a Japanese community sample., Methods and Procedures: Surveys were administered to 1373 Japanese adults who were parents to children in kindergartens, nursery schools, and elementary schools., Outcomes and Results: The results showed that parents with higher levels of autistic traits had more parenting difficulties. Even after controlling for children's sex, age, and emotional/behavioral problems, paternal impaired communication and maternal poor attention switching, impaired communication, and lack of imagination were related to higher parenting difficulties, while a higher maternal level of attention to detail was associated with lower difficulties in parenting., Conclusions and Implications: The findings of this study highlight the importance of focusing on parental autistic traits and providing appropriate parenting support considering these traits., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Relebactam is a novel β-lactamase inhibitor of Ambler class A and C β-lactamases that has been developed in combination with imipenem/cilastatin for the treatment of carbapenem-resistant bacterial infections. In this study, we evaluated the in vitro antibacterial activity of imipenem/relebactam (IMR) against imipenem-nonsusceptible Enterobacterales and Pseudomonas aeruginosa isolates from Japan. Two sets of antibacterial susceptibility tests were conducted according to the susceptibility testing standard of the Clinical and Laboratory Standards Institute. In the first set, antibacterial susceptibility as measured by the MIC 50/90 (MIC range) of IMR was assessed for the following 61 imipenem-nonsusceptible strains: 2 Enterobacter cloacae complex (not determined [0.25 μg/mL]), 33 Klebsiella aerogenes (0.5/1 μg/mL [0.5 to 1 μg/mL]), 2 Serratia marcescens (not determined [1 to 2 μg/mL]), and 24 P. aeruginosa (2/128 μg/mL [0.25 to >128 μg/mL]). In the second set, antibacterial susceptibility was assessed for the following 8 imipenem-nonsusceptible strains: 4 Escherichia coli, 1 E. cloacae complex and 3 Klebsiella pneumoniae. The MIC ranges of IMR for these strains were 0.25 to 0.5 μg/mL, 0.5 μg/mL, and 0.5 to 16 μg/mL, respectively. The antibacterial activity of IMR was similar to or lower than that of amikacin and comparable to or greater than those of other reference drugs. In conclusion, IMR has shown antibacterial activity against clinical isolates from Japan and, therefore, is expected to become a new therapeutic option for carbapenem-resistant infections in Japan. IMPORTANCE Carbapenem-resistant Enterobacterales and carbapenem-resistant Pseudomonas aeruginosa strains pose a global threat. Antibacterial activity of imipenem/relebactam (IMR) against clinical isolates of these bacteria from several global regions has been shown; however, as yet there are no reports on Japanese isolates. In this study, we evaluated the in vitro antibacterial activity of IMR against imipenem-nonsusceptible Enterobacterales and Pseudomonas aeruginosa isolates from Japan. The antibacterial activity of IMR against imipenem-nonsusceptible Enterobacterales was generally comparable to that of amikacin (AMK) and comparable to or higher than those of other reference drugs tested. The antibacterial activity of IMR against imipenem-nonsusceptible P. aeruginosa isolates was lower than that of AMK but comparable to or higher than those of other drugs. These results support the use of IMR as a new treatment option for infections due to Enterobacterales and P. aeruginosa strains that are resistant to existing β-lactams and other antibacterial agents.

Background: Obesity is reported to be a predictor of adverse clinical events in coronavirus disease 2019 (COVID-19) in Western countries. However, there are limited data reported regarding the prognostic impact of obesity in Asian patients. We investigated the relationship between body mass index (BMI) and in-hospital outcomes in 580 Japanese patients with cardiovascular disease and/or risk factors and who were admitted for COVID-19 infection using data from 49 hospitals in Japan., Methods: We analyzed data from the Clinical Outcomes of COVID-19 Infection in Hospitalized Patients with Cardiovascular Disease and/or Risk Factors (CLAVIS-COVID) registry. BMI was classified into four groups accordance with the definition of the Japan Society for the Study of Obesity, as follows: underweight, <18.5 kg/m 2 ; normal range, 18.5 to <25 kg/m 2 ; pre-obese, 25 to 30 kg/m 2 ; and obese, ≥30 kg/m 2 ., Results: In-hospital death occurred in 15.0% (n=87) of the patients and intubation was performed for 139 (24.0%) patients. In a multivariate analysis, we found a significant association between higher BMI and in-hospital mortality [underweight: hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.23-0.97; p=0.041; pre-obese: HR 1.46, 95%CI 0.84-2.55; p=0.18; and obese: HR 3.28, 95%CI 1.34-8.02; p=0.009 vs. normal range]. In contrast, the association between BMI and the intubation rate was not statistically significant., Conclusions: Obesity was associated with a stepwise increase in the risk of in-hospital mortality in Japanese patients with COVID-19 infection. The threshold BMI for the increased risk of a worse outcome was 30, which was much lower in comparison to Western countries., (Copyright © 2021. Published by Elsevier Ltd.)

In Japan, the first endoscopic surgery, a laparoscopic cholecystectomy, was performed in 1990. Since then, operative procedures have been standardized, and the safety and efficacy of endoscopic surgery have been evaluated. In accordance with the social acceptance of endoscopic surgery as a less invasive type of surgery, the number of endoscopic procedures performed has increased in all surgical domains. The Japan Society for Endoscopic Surgery (JSES) has played an important role in the development of endoscopic surgery in Japan. Notably, a technical skills certification system for surgeons was established by the JSES to train instructors on how to teach safe endoscopic surgery. Furthermore, the JSES has conducted a national survey every 2 years. In 2019, 291,792 patients underwent endoscopic surgery in all surgical domains, such as abdominal, thoracic, mammary and thyroid gland, cardiovascular, obstetrics and gynecology, urologic, orthopedic, and plastic surgery. The 15th National Survey of Endoscopic Surgery conducted by the JSES demonstrated the status of laparoscopic surgery in Japan in 2018-2019., (© 2021 Asia Endosurgery Task Force and Japan Society of Endoscopic Surgery and John Wiley & Sons Australia, Ltd.)

Background: Understanding the degree of motor paralysis in stroke patients is important for assessing the severity of functional impairment and predicting functional prognosis. Fugl-MeyerAssessment for the lower extremities (FMA-LE)is a commonly used measure with high reliability and validity, but there is no official translated Japanese version of FMA-LE., Objectives: This study aimed to develop Japanese FMA-LE and verify its reliability and validity in patients with acute stroke., Methods: The Japanese FMA-LE was developed following a standardized translation process. The reliability and validity were evaluated in 50 stroke patients at an acute care hospital. Validity was examined by determining the correlation between FMA-LEand Brunnstrom Recovery Stage (BRS), as well as Short Physical Performance Battery (SPPB). Intra-raterand inter-raterrelative reliabilities were evaluated by calculating intra-classcorrelation coefficients (ICCs). Absolute reliability was assessed by determining the standard error of the measurement and minimum detectible change (MDC). Systematic error was also assessed., Results: FMA-LEtotal score was high correlated with BRS (ρ = 0.73,p < .01) and moderately correlated with SPPB (ρ = 0.69,p < .01). For intra-raterreliability, ICC was 0.98 (p < .01), only fixed systematic error was observed (p < .01), and MDC of the FMA-LEtotal score was 1.24. For inter-raterreliability, ICC was 0.98 (p < .01), no systematic error was observed, and MDC of the FMA-LEtotal score was 3.23., Conclusions: The Japanese FMA-LE was reliable, valid, and useful for evaluating lower extremity function of acute stroke patients.

To estimate the health-promoting effects of Lacticaseibacillus paracasei (previously Lactobacillus casei ) strain Shirota (LcS) that reached the lower gastrointestinal tract alive, we investigated the characteristics of gut microbiome, organic acid profiles, defecatory symptoms and serum viral antibody indexes of healthy Japanese adults between the group in whom live LcS was detected or not from stool. The β-diversity index of the gut microbiome constituted a significant difference between the live-LcS-detected-group (LLD) and the live-LcS-not-detected-group (LLnD). In the LLD, the Bifidobacteriaceae, Lactobacillaceae , and Coriobacteriaceae counts were significantly higher, and the succinate concentration was significantly lower than that in the LLnD. The serum herpes simplex virus (HSV) immunoglobulin (Ig)M antibody index in the LLD tended to be lower than that of the LLnD in HSV IgG-positive subjects. Of the LLD, those in the fermented milk products containing LcS (FML)-high-frequency-group (FML-HF) and those in the FML-low-frequency-group (FML-LF) had different gut microbiome and organic acid profiles. However, the pattern of differences between FML-HF and FML-LF was dissimilar those between LLD and LLnD. In contrast, among subjects with FML-LF, those in the group with LLD in stool (LF-LLD) and those in the LLnD in stool (LF-LLnD) showed a similar pattern of differences in their gut microbiome and organic acid profiles as those in the LLnD and LLD. The LLD and LF-LLD commonly had lower caloric and carbohydrate intakes from the diet than their respective control groups. In this study, we found that the presence of live LcS in stool is associated with a healthy gut environment and inhibition of the reactivation of latently infected viruses in the host. However, these health-promoting effects on the host were not related to the frequency of FML intake. Furthermore, dysbiosis of the gut microbiome and diet including caloric intake was related to the viability of ingested LcS in the gut.

The daily rest period (DRP) is the daily inter-work interval and can include a sleep opportunity, leisure time, and other non-work time. A longer DRP may allow workers to increase time in bed (TIB) and adjust sleep timing, and that may reduce sleep problems such as short sleep duration, sleep debt, social jetlag, and poor sleep quality. The present study examined the longitudinal association between the DRP and these sleep problems among Japanese daytime workers. The DRP, TIB on workdays, sleep quality (Pittsburgh Sleep Quality Index [PSQI]), sleep debt and social jetlag were measured in November 2016 (n = 10,000) and February 2019 (n = 3,098). Of these, 955 permanent daytime workers were divided into five groups based on the change in the DRP duration: shortened ≥2 hr, shortened ≥1 hr, no change (<1 hr), extended ≥1 hr and extended ≥2 hr. Linear mixed-model analysis revealed significant interaction (group × time) effects on the TIB, PSQI score and sleep debt (all p < 0.001), but not on social jetlag (p = 0.476). Post hoc comparisons revealed that the TIB was decreased, and the sleep debt was increased in the shortened ≥2 hr group, whereas the TIB was increased and PSQI score was improved in the extended ≥2 hr group (all p < 0.01). These findings suggest that an extension of the DRP improves sleep quantity and quality but not sleep debt and social jetlag. Aside from extending the DRP, ensuring a sufficient sleep duration and adjusting sleep timing during the DRP may also be needed to prevent sleep problems., (© 2021 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Aim: Although frailty could be reversible by early diagnosis and interventions, it lacks definite diagnostic criteria. The Kihon Checklist is a 25-item questionnaire that diagnoses frailty with a cutoff score of 7/8. The Questionnaire for Medical Checkup of Old-Old (QMCOO) was recently established and used for medical checkups among Japanese older adults, but no method or cutoff score for diagnosing frailty has been established. Thus, we aimed to diagnose frailty using the QMCOO and to determine its cutoff score by comparing it with that of the Kihon Checklist., Methods: We recruited 223 older adults in Yasugi City and Yonago City to answer all the questions in the Kihon Checklist and the QMCOO at the same time. Those scoring ≥8 for the Kihon Checklist (n = 38) were diagnosed as frail. We also determined the cutoff score for frailty for the QMCOO and examined which questionnaire items affected the frailty status., Results: The QMCOO and the Kihon Checklist score showed a significant positive correlation (r = 0.670, P < 0.001). The area under the curve was 0.851. A cutoff score of 3/4 for the QMCOO represented the best results (sensitivity, 76.3%; specificity, 88.1%; and accuracy, 86.1%). Multiple linear regression analysis revealed that subjective health status, body weight loss, slowness, and forgetfulness still affected the frailty status., Conclusions: A cutoff score of 3/4 for the QMCOO might be effective in diagnosing frailty. Geriatr Gerontol Int 2022; 22: 127-131., (© 2021 Japan Geriatrics Society.)

Objectives: Karoshi problems (overwork-related deaths and disorders caused by cerebrovascular and cardiovascular diseases) still occur in Japan. Truck drivers, who are in one of the riskiest occupations, are reported to show an increased prevalence of hypertension, obesity, hyperlipidemia, and diabetes, which are characteristic of Karoshi. Their health problems also include excessive fatigue. This cross-sectional study aimed to examine the association between work-life factors and health disorders/excessive fatigue among Japanese truck drivers., Methods: We distributed a questionnaire regarding work hours, health status, lifestyle, burden of driving, and excessive fatigue to 5,410 truck drivers and collected a total of 1,947 responses, all from males. The association between work-life factors and health outcomes was evaluated by multivariable logistic regression analysis adjusted for age, drinking, and smoking status., Results: The prevalence rates of obesity, hypertension, hyperlipidemia, diabetes, cardiovascular disease, cerebrovascular disease, and excessive fatigue were 22.2%, 19.3%, 8.5%, 5.6%, 2.5%, 0.7%, and 6.0%, respectively. Significant associations were observed for long-haul trips (two days or more) with obesity (adjusted odds ratio 1.5 [95% Confidence Interval 1.1-2.1]), local and night trips with hypertension (1.5 [1.0-2.2]), early morning awakening on workdays with obesity (1.5 [1.1-2.1]), being indoor-oriented on weekends with hypertension (1.5 [1.1-2.0]); and heavy burden of driving at night with hyperlipidemia (2.0 [1.3-3.0]). The adjusted odds ratios were significant for waking after sleep onset (2.6 [1.2-5.3]) and lack of sleep satisfaction (2.7 [1.4-5.1]) on workdays, less than six hours of sleep (2.8 [1.0-7.8]) and lack of sleep satisfaction (2.8 [1.5-5.2]) on weekends, 0-3 days off per month (3.6 [1.3-10.2]), and heavy burden of driving at night (2.2 [1.0-4.8]) with excessive fatigue., Conclusions: The present findings highlight that night and early morning work, heavy burden of night driving, and the resultant decreases in the quality and quantity of sleep may represent shared risk factors for health disorders and excessive fatigue among truck drivers. Adequate measures should be taken to limit the amount of night and early morning work, reduce the burden of night driving, and ensure days off for sleep opportunities and leisure activities, with the goal of preventing Karoshi.

Aspergillus section Nigri, a group of black Aspergillus, has several cryptic species that were recently discovered to be intrinsically resistant to azole antifungals. In this study, susceptibility testing of 35 clinical isolates of Aspergillus tubingensis and Aspergillus welwitschiae in Japan was carried out using microdilution method. Strains tolerant to itraconazole in A. tubingensis (14/17 strains) and A. welwitschiae (6/18 strains) were discovered with hyphal growth and conidial germination above the minimal inhibitory concentration by microscopic observation, while no resistant strain was observed macroscopically. In contrast, no strain with reduced susceptibility to voriconazole, posaconazole, and amphotericin-B was found. Further examination may be required to determine the susceptibility of cryptic species in Aspergillus section Nigri to antifungals.

Background: Pompe disease is an autosomal recessive inherited metabolic disorder caused by a deficiency of the acid α-glucosidase (GAA). Pompe disease manifests as an accumulation of lysosomal glycogen in the skeletal and heart muscle. We conducted newborn screening (NBS) for Pompe disease in Japan from April 2013 to October 2020 to determine the feasibility and utility of NBS for Pompe disease., Results: From the 296,759 newborns whose enzyme activity was measured, 107 of which underwent GAA analysis, we found one patient with infantile-onset Pompe disease (IOPD) and seven with potential late-onset Pompe disease (LOPD). We identified 34 pseudodeficient individuals and 65 carriers or potential carriers. The frequency of patients with IOPD was similar to that in the United States, but significantly lower than that in Taiwan. One patient with IOPD underwent early enzyme replacement therapy within a month after birth before presenting exacerbated manifestations, whereas those with potential LOPD showed no manifestations during the follow-up period of six years., Conclusions: The frequency of IOPD in Japan was similar to that in the United States, where NBS for Pompe disease is recommended. This indicates that NBS for Pompe disease may also be useful in Japan. Therefore, it should be used over a wider region in Japan., (© 2021. The Author(s).)

While mRNA vaccines against SARS-CoV-2 are exceedingly effective in preventing symptomatic infection, their immune response features remain to be clarified. In the present prospective study, 225 healthy individuals in Japan, who received two BNT162b2 doses, were enrolled. Correlates of BNT162b2-elicited SARS-CoV-2-neutralizing activity (50% neutralization titer: NT 50 ; assessed using infectious virions) with various determinants were examined and the potency of sera against variants of concerns was determined. Significant rise in NT 50 s was seen in sera on day 28 post-1st dose. A moderate inverse correlation was seen between NT 50 s and ages, but no correlation seen between NT 50 s and adverse effects. NT 50 s and SARS-CoV-2-S1-binding-IgG levels on day 28 post-1st dose and pain scores following the 2nd dose were greater in women than in men. The average half-life of NT 50 s was ~ 68 days, and 23.6% (49 out of 208 individuals) failed to show detectable neutralizing activity on day 150. While sera from elite-responders (NT 50 s > 1,500: the top 4% among the participants) potently to moderately blocked all variants of concerns examined, some sera with low NT 50 s failed to block the B.1.351-beta strain. Since BNT162b2-elicited immunity against SARS-CoV-2 is short, an additional vaccine or other protective measures are needed., (© 2021. The Author(s).)

Background: Having a late chronotype, that is, the tendency to go to sleep and wake up at later hours, influences an individual's physical and mental health. Despite a few studies noting the association of chronotype with healthy dietary patterns, this relationship remains unclear., Purpose: This study aimed to describe the association of chronotype with healthful and unhealthful plant-based diet quality in female Japanese undergraduate students., Design: Cross-sectional., Participants and Setting: A total of 218 female university students in Tokyo, Japan., Main Outcome Measures: Healthful and unhealthful plant-based dietary index-Japanese version (hPDI-J and uPDI-J), calculated using the validated brief-type self-administered diet history questionnaire., Statistical Analyses Performed: A five-model stepwise multiple linear regression analysis was conducted. Independent variables were hPDI-J and uPDI-J scores, and dependent variables were various lifestyle habits related to the circadian rhythm and demographic characteristics., Results: Mean (standard deviation) sleep duration, midpoint of sleep, sleep latency time, and social jetlag were 411 (60) min, 03:56 (00:57), 21 (27) min, and 50 (39) min, respectively. Chronotype and several variables, such as residential status, energy and alcohol intake, and nutritional knowledge, were associated with healthful and unhealthful plant-based diet quality. Individuals who had higher hPDI-J scores were more likely to have an earlier chronotype (β = -0.168, P = 0.019) and better nutritional knowledge (β = 0.164, P = 0.022) than those with lower hPDI-J scores. Individuals were more likely to have higher uPDI-J scores if they were living alone (β = -0.301, P < 0.001), had a later chronotype (β = 0.181, P = 0.001), higher frequency of snacking (β = 0.164, P = 0.019), lower total energy (β = -0.445, P < 0.001), and worse nutritional knowledge (β = -0.172, P = 0.001)., Conclusion: This study provided new evidence as to the relationship between sleep and dietary habits, the interaction of which may affect women's health., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background/aim: To evaluate the incidence and grade of radiation pneumonitis after volumetric modulated arc therapy (VMAT) performed for the treatment of non-small cell cancer (NSCLC)., Patients and Methods: Fifty consecutive non-surgical candidates with NSCLC underwent VMAT. Thirty-five patients had stage-III tumors and 15 had recurrent tumors. The prescribed radiation dose for the gross tumor and the elective nodal area was 69 Gy in 30 fractions and 51 Gy in 30 fractions, respectively., Results: Radiation pneumonitis developed in 38 patients (76%, 38/50), and grade ≥2 radiation pneumonitis developed in 11 patients (22%, 11/50). The percentage of lung volume that received a dose in excess of 5 Gy (V5), V10, V20, V30, and the mean lung dose (MLD) in the bilateral and ipsilateral lung were significantly associated with the development of grade ≥2 radiation pneumonitis., Conclusion: The incidence and degree of radiation pneumonitis are acceptable following treatment of NSCLC with VMAT., (Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Currently, the same-day polyethylene glycol-electrolyte lavage solution (PEG-ELS) regimen is particularly recommended for afternoon colonoscopy as an alternative to the split-dose regimen in western countries. However, in Japan, the split-dose regimen has never been used as a standard colonoscopy preparation regimen. The aim of this study was to compare the efficacy and tolerability of split-dose PEG containing ascorbic acid (ASC) with same-day single dose PEG-ASC in Japan.This was a single-blinded, non-inferiority, two-center, randomized, controlled study. In-hospital patients were randomized to the same-day regimen or the split regimen using a web-based registry system. The same-day group was instructed to take 5 mL of sodium picosulfate in the evening, and on the day of the colonoscopy, they took 1.5 L of PEG-ASC. The split group was instructed to take 1 L of PEG-ASC before the day of colonoscopy, followed by another 1 L of PEG-ASC on the day of colonoscopy. Bowel cleansing was evaluated by the Boston Bowel Preparation Scale.A total of 153 patients were randomized to either the same-day group (n=78, males 60.0%, mean age 62.7 years) or the split group (n=75, 61.3%, 61.9 years). The rates of successful bowel cleansing were 83.3% in the same-day group vs. 92.0% (83.4%-97.0%) in the split group, P=0.10). No serious adverse events occurred in the study population. However, more patients in the same-day group were willing to repeat the same preparation regimen (P<0.001). The split-dose regimen was not inferior to the same-day regimen with respect to the efficacy of bowel preparation, but the patients preferred the same-day regimen., Competing Interests: Masahiro Tajika received honoraria from EA Pharma Co., Ltd. All other authors have no conflicts of interest to declare for this work.