Search

Based on the results of the IFMIF/EVEDA project in the broader approach (BA) activities, the conceptual design of the Advanced Fusion Neutron Source (A-FNS) to obtain irradiation data of DEMO blanket materials is under consideration in Japan. This paper describes the progress of the A-FNS conceptual design, which consists of a 40 MeV, 125 mA deuteron beam, a liquid lithium target system, and a test and post-irradiation test facilities. the main objectives of the A-FNS are the acquisition of RAFM irradiation data up to 2035 and the tritium recovery test on the blanket. In addition, it is expected to be used for various neutron researches. The technical design activities of the A-FNS are focused on improvement of the lithium target design, review of impurity criteria, remote handling, and irradiation application plan. [ABSTRACT FROM AUTHOR]

Following the severe accident at the Fukushima Daiichi nuclear power plant in 2011, recrystallized FeCrAl-ODS claddings have been developed in Japan as an accident-tolerant fuel (ATF) to mitigate the extent of oxidation reactions with hot steam. This paper presents an overview of the alloy design and the process used to manufacture the recrystallized cladding, together with a analysis of the applicability of these alloys as BWR fuel cladding and a summary of the results of simulated severe accident performance. A synergistic effect of co-addition of 12 mass% Cr and 6 mass% Al was found to suppress steam oxidation by a stable Al 2 O 3 scale formation and to inhibit a brittle αʹ precipitate after aging. The incorporation of 0.4 mass% Zr greatly improved not only the high temperature strength by replacing coarse Y-Al oxide particles with finer Y-Zr particles, but also the oxidation resistance at temperatures above 1673 K. These excellent performances are associated with the excess oxygen content. It was verified that core excess reactivities affected by the increased neutron absorption by Fe, Cr, Al can be compensated by reducing the thickness to half that of Zircaloy cladding, while maintaining mechanical integrity. A simulated design basis Loss of Coolant Accident (LOCA) event with assessment of post-LOCA ductility confirmed that FeCrAl-ODS cladding provided a greater safety margin along with exceptional high temperature strength and a significantly higher integral LOCA burst temperature compared with wrought FeCrAl alloy (C26M) and Zircaloy. An analysis using the MAAP 5.05b SA code indicated that melting of the Zircaloy core could be slightly accelerated due to release of the huge amount of exothermic reaction heat in the case of small amount of coolant injection. In contrast, the water injection always acts toward cooling the FeCrAl-ODS core. [ABSTRACT FROM AUTHOR]

High power, long pulse millimeter (mm) wave experiments of the RF test stand (RFTS) of Japan Atomic Energy Agency (JAEA) were performed. The system consists of a 1 MW/170 GHz gyrotron, a long and short distance transmission line (TL), and an equatorial launcher (EL) mock-up. The RFTS has an ITER-relevant configuration, i.e., consisted by a 1 MW-170 GHz gyrotron, a mm wave TL, and an EL mock-up. The TL is composed of a matching optics unit, evacuated circular corrugated waveguides, 6-miter bends, an in-line waveguide switch, and an isolation valve. The EL-mock-up is fabricated according to the current design of the ITER launcher. The Gaussian-like beam radiation with the steering capability of 20°-40° from the EL mock-up was also successfully proved. The high power, long pulse power transmission test was conducted with the metallic load replaced by the EL mock-up, and the transmission of 1 MW/800 s and 0.5 MW/1000 s was successfully demonstrated with no arcing and no damages. The transmission efficiency of the TL was 96%. The results prove the feasibility of the ITER electron cyclotron heating and current drive system. [ABSTRACT FROM AUTHOR]

The FeCrAl-oxide dispersion strengthened (ODS) alloy is a promising candidate alloy for the accident tolerant fuel (ATF) cladding of light water reactors (LWRs) and has been recently developed in Japan. This paper reports on the progress of the development of accident tolerant FeCrAl-ODS fuel claddings for boiling water reactors (BWRs) in Japan. Both experimental and analytical studies were conducted to evaluate the influence of implementation of the FeCrAl-ODS fuel cladding to the current BWRs. In the experimental study, key material properties of FeCrAl-ODS fuel cladding have been obtained and accumulated using bar, sheet and tube-shaped materials to support the evaluations in the analytical study. In the evaluation at normal operating conditions, strength and ductility, corrosion property, tritium permeability, wear property, resistance to iodine stress corrosion cracking (SCC) and weldability were examined. A preliminary assessment of compatibility of the FeCrAl-ODS fuel cladding with the current recycling system in Japan was also conducted. In the evaluation of the design basis accident and the beyond design basis accident, strength, steam oxidation property, resistance to water quenching during a loss-of-coolant accident (LOCA) and the LOCA burst property were examined. In order to evaluate the influence of implementation of the FeCrAl-ODS cladding to the current BWRs, the core characteristics and the fuel behavior were evaluated in the analysis study at the normal operating condition. The analysis for the 9 × 9-type and the 10 × 10-type fuel assemblies and the reactor type of the Advanced BWR (ABWR) revealed a good applicability of FeCrAl-ODS fuel cladding. Finally, the challenges and perspectives found in the program are highlighted to enhance international collaborations to promote the development of the FeCrAl-ODS fuel cladding. [ABSTRACT FROM AUTHOR]

Objective: To examine carotid intima-media thickness (IMT), predictors of its progression, and its relationship with incident coronary heart disease (CHD) in type 2 diabetic Japanese patients.Research Design and Methods: Carotid IMT of 287 subjects with type 2 diabetes (mean age 61.6 years) without CHD or cerebrovascular disease was examined at baseline and after a mean follow-up of 3.1 years.Results: The annual progression of IMT (means +/- SEM) was 0.04+/-0.004 mm/year. Stepwise multivariate analysis demonstrated that independent risk factors for progress of IMT were the initial IMT (P<0.001), the average HbA1c level (P<0.001), and age (P = 0.001). Both the initial IMT (odds ratio [OR] 4.9, 95% CI 1.7-14.1) and a low average HDL cholesterol (OR 0.2, 0.1-0.8) were identified as predictors of incident nonfatal CHD (angina pectoris or nonfatal myocardial infarction; 3-year incidence 10.1%) after adjusting for age, sex, average HbA1c, and other risk factors.Conclusions: The predictors of the progression of carotid IMT in Japanese type 2 diabetic subjects were its baseline thickness and the average HbA1c during the follow-up. Baseline carotid IMT and low HDL cholesterol predicted the incidence of nonfatal CHD. [ABSTRACT FROM AUTHOR]

Abstract: This paper reports R&D progress of the MeV class accelerator, beam focussing technique and a high voltage (HV) bushing toward the ITER Neutral Beam system at JAEA. A H− ion beam of 320mA (current density: 140A/m2) was successfully accelerated up to 796keV by fixing air leak in the ion source chamber caused by heat loading due to backstream positive ions. From analyses of a three-dimensional beam trajectory, a countermeasure against beamlet deflection due to space charge repulsion among beamlets was identified to compensate the deflection by proper aperture offset in the electron suppression grid. For development of the HV bushing, a half-size (Ø800mm) mockup single stage bushing was manufactured and tested, that demonstrated the dc voltage holding capability of up to 220kV in a condition with vacuum inside. Electrostatic analyses and design of the HV bushing are in progress, in which some design improvements are suggested to reduce electric field strength on the surface of ceramic insulator. [Copyright &y& Elsevier]

As a candidate accident tolerant fuel cladding material, the high temperature oxidation behaviour of an Oxygen Dispersion Strengthened (ODS) Fe–12Cr–6Al alloy has been examined in isothermal air and steam environments. While the oxidation behaviour of FeCrAl has been extensively studied, very little has been reported in the literature on FeCrAl-ODS, which is the focus of this manuscript. By conducting Thermogravimetric Analysis (TGA), oxidation experiments were performed on specimens of Fe–12Cr–6Al-ODS at temperatures up to 1400 °C in air and up to 1215 °C in high purity steam. Oxidation kinetics were evaluated by calculating reaction rate constants and activation energies. The formation of an alumina scale was correlated to kinetics results from TGA by coupling Scanning Electron Microscopy (SEM) with Energy Dispersive X-ray Spectroscopy (EDS) line scans to investigate the chemical composition of the primary oxide layer, local oxidation effects, as well as the bulk alloy material. Electron Probe Micro-Analysis (EPMA) point scans were applied to the heavily oxidized specimen to achieve an accurate composition profiling of areas of interest. Finally, thermodynamic calculations were performed to interpret the formation of the complex oxide layer. These experiments support research efforts for the development of accident tolerant fuel technologies at Nippon Nuclear Fuel Development Co., Ltd. [ABSTRACT FROM AUTHOR]

Purpose Currently, in Japan, implantable ventricular assist devices (VAD) are limited to bridge to transplantation (BTT). Therefore, left ventricular repair (LVR) has been applied to patients with severe heart failure who were ineligible for cardiac transplantation. We compared the mid-term results of surgical management with LVR and VAD for advanced heart failure. Methods We enrolled 19 patients with advanced heart failure to undergo LVR (n=13) or implantation of VAD (n=6) from 2008 to 2015 in our institute. Procedures in LVR group included papillary muscle approximation in 13 patients, Batista type left ventricular repair in 6, Overlap in 1, and septal anterior ventricular exclusion in 1. The VAD used in this study was HeartMateII (Thoratec, Pleasanton, CA). All patients had symptoms of New York Heart Association class IV but 9 patients class III in LVR group. Results Patients in Group LVR were older than those in Group VAD (Group LVR 63±14 years old vs Group VAD 44±17, p = 0.036). There were no significant differences in preoperative LV EF (Group LVR 21.2±9.1 vs Group VAD 20.3±10.0 %, p = 0.83) or LV end-diastolic dimension (Group LVR 72±13 vs Group VAD 70±12 mm, p = 0.71) between the groups. There was no significant differences in preoperative BNP values (Group LVR 914±500 vs Group VAD 615±241, p = 0.11). Group LVR had 2 in-hospital death after surgery, but VAD had none. There were no significant differences in LV EF (Group LVR 20.2±910.8 vs Group VAD 27.6±19.2 %, p = 0.41) or LV end-diastolic dimension (Group LVR 65±6 vs Group VAD 57±14 mm, p = 0.18) between the groups, immediately after surgery. Follow-up was 2.1±1.8 years long. There were total 10 deaths in Group LVR, but no patients died in Group VAD and 1 patient had transplantation during follow-up. Group VAD had superior 5-year survival rates (Log-rank: Group LVR 9 % vs Group VAD 100 %, p = 0.010.) Conclusion Treatment with VAD in patients with advanced heart failure significantly improved survival compared with LVR. VAD as destination therapy should be warranted in Japan. [ABSTRACT FROM AUTHOR]

Introduction: To verify the value of the pathological criteria for additional treatment in locally resected pT1 colorectal carcinoma (CRC) which have been used in the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines since 2009., Methods: We enrolled 4,667 patients with pT1 CRC treated at 27 institutions between July 2009 and December 2016 (1,257 patients with local resection alone [group A], 1,512 patients with additional surgery after local resection [group B], and 1,898 patients with surgery alone [group C]). All 5 factors of the JSCCR guidelines (submucosal resection margin, tumor histologic grade, submucosal invasion depth, lymphovascular invasion, and tumor budding) for lymph node metastasis (LNM) had been diagnosed prospectively., Results: Any of the risk factors were present in 3,751 patients. The LNM incidence was 10.4% (95% confidence interval 9.4-11.5) in group B/C patients with risk factors, whereas it was 1.8% (95% confidence interval 0.4-5.3) in those without risk factors ( P < 0.01). In group A, the incidence of recurrence was 3.6% in patients with risk factors, but it was only 0.4% in patients without risk factors ( P < 0.01). The disease-free survival rate of group A patients classified as risk positive was significantly worse than those of groups B and C patients. However, the 5-year disease-free survival rate in group A patients with no risk was 99.6%., Discussion: Our large-scale real-world multicenter study demonstrated the validity of the JSCCR criteria for pT1 CRC after local resection, especially regarding favorable outcomes in patients with low risk of LNM., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

The increased risk of adverse drug reactions due to the concomitant use of antipsychotics is problematic in the treatment of schizophrenia. Therefore, the simultaneous analysis of their plasma concentrations is required. In this study, we developed a simultaneous liquid chromatography/tandem mass spectrometry (LC-MS/MS) method for analyzing plasma antipsychotics approved in Japan for therapeutic drug monitoring (TDM) applications. First, we counted the prescriptions for 16 antipsychotics and concomitant drugs used at the Tohoku University Hospital. LC-MS/MS was used for the simultaneous analysis of 16 antipsychotics and four drug metabolites. This analysis was conducted using a combination of selected reaction monitoring mode and reversed-phase chromatography. Following the examination of the MS/MS and LC conditions, an analytical method validation test was conducted. The developed method was used to analyze plasma antipsychotic levels in patients with schizophrenia. One-third of the patients received treatment with multiple antipsychotics. Under LC-MS/MS conditions, LC separation was performed using a combination of a C18 column and ammonium formate-based mobile phases with a gradient flow. The calibration curves were optimized by adjusting the ion abundance, and 11 compounds met the criteria for intra- and inter-day reproducibility tests. Some stability test results did not meet these criteria; therefore, further investigation is required. The developed method permitted the measurement of all the plasma parameters, including concentrations above the therapeutic range. Therefore, this method may be useful in the daily TDM practice of antipsychotics., (© 2024. The Author(s).)

Background: Maintenance avelumab is currently recommended for patients with unresectable and/or metastatic (mUC) achieving at least stable disease (SD) on first-line platinum-based chemotherapy (1L-CT). Pembrolizumab is an alternative therapeutic avenue for this patient cohort in clinical practice. We investigated real-world data, focusing on the correlation between response to 1L-CT and oncological efficacy of subsequent immune checkpoint inhibitor (ICI) therapy with avelumab or pembrolizumab., Methods: A multicenter database registered 626 patients with mUC diagnosed from 2008-2023; among these, 175 receiving 2-6 cycles of 1L-CT followed by ICI therapy. Patients were categorized based on response to 1L-CT using the Response Evaluation Criteria in Solid Tumors (v1.1). Objective response rate on ICI, progression to ICI-free survival (ICI-PFS), and overall survival from start of 1L-CT were compared between avelumab-treated and pembrolizumab-treated patients in each response subgroup., Results: ICI-PFS was significantly longer in patients achieving partial response on 1L-CT and subsequently receiving pembrolizumab compared to those receiving avelumab. Notably, patients achieving SD on 1L-CT and subsequently receiving pembrolizumab manifested significantly higher objective response rate (14% and 41%, respectively) and prolonged ICI-PFS relative to those receiving avelumab. In contrast, overall survival did not delineate difference between patients treated with avelumab versus pembrolizumab. Similar findings were discerned in the subanalysis of patients having favorable SD (tumor shrinkage, from - 29 to 0%) and unfavorable SD (tumor enlargement, from + 1 to + 19%) on 1L-CT., Conclusions: Our study provides real-world evidence regarding difference of oncological efficacy between maintenance avelumab and subsequent pembrolizumab in patients with mUC who achieved partial response or SD on 1L-CT., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Background: Thoracoscopy is useful for diagnosing unexplained pleural effusions. A sufficient specimen volume is often difficult to obtain using forceps biopsies (FBs) but can be obtained with pleural cryobiopsies (CBs). This study aimed to assess the utility and safety of CB during thoracoscopy in the Japanese population., Methods: Patients who underwent thoracoscopic CBs at the Japanese Red Cross Medical Center between January 2017 and August 2023 were included in the study. Data were retrospectively analyzed, including clinical data, thoracoscopic findings, specimen size, diagnostic yield, and complications. The number of collected specimens and the freezing time were left to the discretion of the attending physician., Results: Twenty-six patients underwent thoracoscopic CB. Specimens obtained by CB were larger than those obtained by FB. Primary lung cancer was the most common cause of pleural effusion, followed by malignant pleural mesothelioma. CB contributed to the diagnosis in 24 of 26 cases (92.3%) and FB contributed to the diagnosis in 11 of 18 cases (61.1%). Severe fibrosis could be diagnosed in all 3 cases by CB, but not by FB. The common complications of CB included bleeding at the biopsy site and atelectasis, but no severe complications occurred., Conclusions: The utility and safety of thoracoscopic CB for diagnosing pleural effusions in Japan were verified. The diagnostic yield, specimen size, and safety profile of CB support the diagnostic utility of this method., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2024 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Introduction: Although the prognosis of Langerhans cell histiocytosis (LCH) is excellent, the high recurrence rate and permanent consequences, such as central diabetes insipidus and LCH-associated neurodegenerative diseases, remain to be resolved. Based on previous reports that patients with high-risk multisystem LCH show elevated levels of inflammatory molecules, we hypothesised that dexamethasone would more effectively suppress LCH-associated inflammation, especially in the central nervous system (CNS). We further hypothesised that intrathecal chemotherapy would effectively reduce CNS complications. We administer zoledronate to patients with multifocal bone LCH based on an efficacy report from a small case series., Methods and Analysis: This phase II study (labelled the LCH-19-MSMFB study) is designed to evaluate the significance of introducing dexamethasone and intrathecal chemotherapy for multisystem disease and zoledronate for multifocal bone disease in previously untreated, newly diagnosed children, adolescents (under 20 years) and adults under 40 years. The primary endpoint is the 3-year event-free survival rate by risk group of under 20 years and the 3-year event-free survival rate of 20 years and over., Ethics and Dissemination: This study was approved by the Central Review Board of the National Hospital Organisation Nagoya Medical Centre (Nagoya, Japan) on 21 January 2022 and was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp/en-latest-detail/jRCTs041210027). Written informed consent will be obtained from all patients and/or their guardians., Trial Registration Number: jRCTs041210027., Competing Interests: Competing interests: None declared., (© 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: Sarcopenia is characterized by reduced skeletal muscle volume and is a condition that is prevalent among elderly patients and associated with poor prognosis as a comorbidity in malignancies. Given the aging population over 80 years old in Japan, an understanding of malignancies, including colorectal cancer (CRC), complicated by sarcopenia is increasingly important. Therefore, the focus of this study is on a novel and practical diagnostic approach of assessment of psoas major muscle volume (PV) using 3-dimensional computed tomography (3D-CT) in diagnosis of sarcopenia in patients with CRC., Methods: The subjects were 150 patients aged ≥ 80 years with CRC who underwent primary tumor resection at Juntendo University Hospital between 2004 and 2017. 3D-CT measurement of PV and conventional CT measurement of the psoas major muscle cross-sectional area (PA) were used to identify sarcopenia (group S) and non-sarcopenia (group nS) cases. Clinicopathological characteristics, operative results, postoperative complications, and prognosis were compared between these groups., Results: The S:nS ratios were 15:135 for the PV method and 52:98 for the PA method. There was a strong positive correlation (r = 0.66, p < 0.01) between PVI (psoas major muscle volume index) and PAI (psoas major muscle cross-sectional area index), which were calculated by dividing PV or PA by the square of height. Surgical results and postoperative complications did not differ significantly in the S and nS groups defined using each method. Overall survival was worse in group S compared to group nS identified by PV (p < 0.01), but not significantly different in groups S and nS identified by PA (p = 0.77). A Cox proportional hazards model for OS identified group S by PV as an independent predictor of a poor prognosis (p < 0.05), whereas group S by PA was not a predictor of prognosis (p = 0.60)., Conclusions: The PV method for identifying sarcopenia in elderly patients with CRC is more practical and sensitive for prediction of a poor prognosis compared to the conventional method., (© 2024. The Author(s).)

Gram-negative, aerobic, rod-shaped, non-spore-forming, motile bacteria, designated strains F2 T and PGU16, were isolated from the midgut crypts of the bordered plant bug Physopelta gutta , collected in Okinawa prefecture, Japan. Although these strains were derived from different host individuals collected at different times, their 16S rRNA gene sequences were identical and showed the highest similarity to Paraburkholderia caribensis MWAP64 T (99.3 %). The genome of strain F2 T consisted of two chromosomes and two plasmids, and its size and G+C content were 9.28 Mb and 62.4 mol% respectively; on the other hand, that of strain PGU16 consisted of two chromosomes and three plasmids, and its size and G+C content were 9.47 Mb and 62.4 mol%, respectively. Phylogenetic analyses revealed that these two strains are members of the genus Paraburkholderia . The digital DNA-DNA hybridization value between these two strains was 92.4 %; on the other hand, the values between strain F2 T and P. caribensis MWAP64 T or phylogenetically closely related Paraburkholderia species were 44.3 % or below 49.1 %. The predominant fatty acids of both strains were C 16 : 0 , C 17 : 0 cyclo, summed feature 8 (C 18 : 1  ω 7 c /C 18 : 1  ω 6 c ), and C 19 : 0 cyclo ω 8 c , and their respiratory quinone was ubiquinone 8. Based on the above genotypic and phenotypic characteristics, strains F2 T and PGU16 represent a novel species of the genus Paraburkholderia for which the name Paraburkholderia largidicola sp. nov. is proposed. The type strain is F2 T (=NBRC 115765 T =LMG 32765 T ).

Alemtuzumab is used with reduced-toxicity conditioning (RTC) in allogeneic hematopoietic cell transplantation (HCT), demonstrating efficacy and feasibility for patients with inborn errors of immunity (IEI) in Western countries; however, the clinical experience in Asian patients with IEI is limited. We retrospectively analyzed patients with IEI who underwent the first allogeneic HCT with alemtuzumab combined with RTC regimens in Japan. A total of 19 patients were included and followed up for a median of 18 months. The donors were haploidentical parents (n = 10), matched siblings (n = 2), and unrelated bone marrow donors (n = 7). Most patients received RTC regimens containing fludarabine and busulfan and were treated with 0.8 mg/kg alemtuzumab with intermediate timing. Eighteen patients survived and achieved stable engraftment, and no grade 3-4 acute graft-versus-host disease was observed. Viral infections were observed in 11 patients (58%) and 6 of them presented symptomatic. The median CD4 + T cell count was low at 6 months (241/µL) but improved at 1 year (577/µL) after HCT. Whole blood cells continued to exhibit > 80% donor type in most cases; however, 3/10 patients exhibited poor donor chimerism only among T cells and also showed undetectable levels of T-cell receptor recombination excision circles (TRECs) at 1 year post-HCT. This study demonstrated the efficacy and safety of alemtuzumab; however, patients frequently developed viral infections and slow reconstitution or low donor chimerism in T cells, emphasizing the importance of monitoring viral status and T-cell-specific chimerism. (238 < 250 words)., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The 87 th Annual Meeting of the Japanese Circulation Society (JCS2023) was held in March 2023 in Fukuoka, Japan, marking the first in-person gathering after the COVID-19 pandemic. With the theme of "New Challenge With Next Generation" the conference emphasized the development of future cardiovascular leaders and technologies such as artificial intelligence (AI). Notable sessions included the Mikamo Lecture on heart failure and the Mashimo Lecture on AI in medicine. Various hands-on sessions and participatory events were well received, promoting learning and networking. Post-event surveys showed high satisfaction among participants, with positive feedback on face-to-face interactions and the overall experience. JCS2023, attended by 17,852 participants, concluded successfully, marking a significant milestone in post-pandemic meetings, and advancing cardiovascular medicine.

Objective: Real-world evidence regarding enfortumab vedotin for unresectable or metastatic urothelial carcinoma is scarce, particularly in Japan. We investigated real-world data focusing on patient background, previous treatments, response, survival and adverse events in patients receiving enfortumab vedotin., Methods: A multicentre database was used to register 556 patients diagnosed with metastatic urothelial carcinoma from 2008 to 2023; 34 patients (6.1%) treated with enfortumab vedotin were included. Best radiographic objective responses were evaluated using the Response Evaluation Criteria in Solid Tumors (v1.1) during treatments. Overall survival and progression-free survival were estimated (Kaplan-Meier method). Toxicities were reported according to the Common Terminology Criteria for Adverse Events, version 5.0. The relative dose intensity, which could impact oncological outcomes, was calculated., Results: The median number of enfortumab vedotin therapy cycles was 5. The best objective response to enfortumab vedotin was partial response, stable disease and progressive disease in 19 (56%), 5 (15%) and 10 (29%) patients, respectively. The median overall survival and progression-free survival after the first enfortumab vedotin dose were 16 and 9 months, respectively. No significant relationship was observed between survival outcomes after enfortumab vedotin initiation and the enfortumab vedotin relative dose intensity. The median overall survival from first-line platinum-based chemotherapy initiation was 42 months. Twenty-six (76%) patients experienced any grade of enfortumab vedotin-related toxicities; eight (24%) experienced Grades 3-4 toxicities, the most common being skin toxicity (any grade, 47%; Grades 3-4, 12%)., Conclusions: Here, we report real-world evidence for enfortumab vedotin therapy in Japan. Tumour responses and safety profiles were comparable with those of clinical trials on this novel treatment., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Over the past 5 years, the number of Vietnamese migrant workers in Japan has grown rapidly to become the largest group of migrant workers in the country. They hold various statuses of residence and are subjected to multifactorial stressors., Aims: The current study's aim is to investigate the association between psychological distress experienced by Vietnamese workers and their work environment. Another aim is to discuss issues involving migrant workers by comparing the characteristics of workers in the major statuses of residence., Methods: The study applied a cross-sectional design, and included a nationwide self-administered online questionnaire that was conducted in Vietnamese in 2022. The questionnaire included the Kessler Psychological Distress Scale (K10), workplace interpersonal factors as well as factors related to work and health. A multiple logistic regression analysis was conducted to investigate factors associated with psychological distress., Results: Of 933 Vietnamese workers, 37% were grouped as distressed under the K10 cutoff. Fewer opportunities to speak with Japanese co-workers, lower welfare and workload ratings, and the visa statuses including 'Technical Intern Training' were significantly associated with psychological distress. Unexpectedly, those in 'Engineer/Specialist in Humanities/International Services (ESI)' category who are deemed to hold better conditions demonstrated the highest amounts of distress., Conclusion: Outside of unsatisfactory working environments, differing situations depending on status of residence could produce various sources of distress. The difficult aspects of Japan's distinct culture seem to contribute to their distress, especially for those who have more interactions with Japanese co-workers. A push for a multicultural society, where migrant workers can pursue proactive life designs of their own choosing, is warranted.

The aim of this study is to identify the potency of land price as a general indicator of the homebound tendency of neighbourhoods. For this purpose, we focus on the associations between land price and older adults' going-out frequency, while considering the similarities and differences from factors associated with walkability. The study targets are 19,270 individuals living in the Tokyo metropolitan area who are aged 65 years or older who are not certified as needing public long-term care insurance. This study uses a two-step procedure: a) the land price of each neighbourhood is estimated using rent price data from 2010 to 2019 collected by an official Japanese realtor organization; b) the associations between older adults' goingout frequency, according to the 2016 Japan Gerontological Evaluation Study, and the estimated land price of their neighbourhoods is identified using multilevel analysis. The results indicate that land price has strong negative associations with older adults' going-out frequency. Associations between land price or other walkability-associated factors, such as population density, ratio of commercial area, and proximity to the nearest train station, only appear when these factors and land price are included within the same model. The results suggest that, when inspecting homebound tendency in some neighbourhoods, factors relating to the built environment must be considered alongside land prices. Furthermore, the homebound status of older adults is a pressing challenge, especially in neighbourhoods with high land prices., Competing Interests: Declaration of Competing Interest We confirm that this manuscript has not been published elsewhere and is not under consideration in whole or in part by another journal. All authors have approved the manuscript and agree with submission to the Archives of Gerontology and Geriatrics. The authors have no conflicts of interest to declare., (Copyright © 2023. Published by Elsevier B.V.)

Objective: Heparin resistance is often encountered during cardiopulmonary bypass. Heparin dose and activated clotting time target values for the initiation of cardiopulmonary bypass are not yet universally standardized; further no consensus exists on the management of heparin resistance. This study aimed to investigate the current real-world practice on heparin management and anticoagulant treatment for heparin resistance in Japan., Methods: A questionnaire survey was conducted at medical institutions nationwide with which The Japanese Society of Extra-Corporeal Technology in Medicine members are affiliated, targeting surgical cases with cardiopulmonary bypass performed from January 2019 through December 2019., Results: Among 69% (230/332) of the participating institutions, the criterion for heparin resistance was defined as "the target activated clotting time value not reached even with an additional dose of heparin administration". Cases of heparin resistance were reported in 89.8% (202/225) of the responded institutions. Of note, 75% (106/141) of the responded institutions reported heparin resistance associated with antithrombin activity ≥ 80%. Antithrombin concentrate was used in 38.4% (238/619 responses) or third dose of heparin in 37.8% (234/619 responses) for advanced heparin resistance treatment. Antithrombin concentrate was found to be effective in resolving heparin resistance in patients having normal, as well as lower antithrombin activity., Conclusion: Heparin resistance has occurred in many cardiovascular centers, even among patients with normal antithrombin activities. Interestingly, the administration of antithrombin concentrate resolved heparin resistance, regardless of the baseline antithrombin activity value., (© 2023. The Author(s).)

To improve treatment outcomes in patients with colorectal liver metastasis (CRLM), the Joint Committee for Nationwide Survey on CRLM was established by the Japanese Society for Cancer of the Colon and Rectum and the Japanese Society of Hepato-Biliary-Pancreatic Surgery. The aim of the study was to evaluate transition in the characteristics and treatment strategy in CRLM patients and analyze prognostic factors using large-scale data. The present study summarizes the data of patients newly diagnosed between 2015 and 2017 and presents prognostic data of patients newly diagnosed in 2013 and 2014. Survival curves were generated by the Kaplan-Meier method and compared by log-rank test. Multivariate analyses were carried out using Cox proportional hazard modeling. The data of 4502 patients newly diagnosed with CRLM between 2015 and 2017 and the prognostic data of 2427 patients diagnosed in 2013 and 2014 are included. Regarding the 2013 and 2014 prognostic data, the 5-year overall survival (OS) rates of patients who underwent hepatectomy alone was 59.8%. Multivariate analyses identified age at diagnosis of CRLM ≥70 years, concomitant extrahepatic metastasis at diagnosis of CRLM, tumor depth of primary lesion ≥subserosa/pericolic or perirectal tissue, mutant KRAS status, number of CRLM ≥5, maximum diameter of CRLM >5 cm, and surgical curability R1/R2 as independent predictors of OS. Analysis of the latest nationwide database of patients diagnosed with CRLM revealed changes in patients and oncological characteristics, a transition in treatment strategy, and different independent prognosticators to those reported previously., (© 2022 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: The Japanese Society of Hepato-Biliary-Pancreatic Surgery (JSHBPS) nomogram was developed to predict disease-free survival in patients with colorectal liver metastases (CRLM) undergoing upfront hepatectomy. However, the utility of the nomogram in patients with resected CRLM remains unknown in the current situation in which treatment strategies are changing with advances in drugs., Methods: Patients in the initial nomogram cohort (n = 727) and validation cohort (n = 2225) were divided into the upfront hepatectomy and preoperative chemotherapy groups. The nomogram was validated by measuring calibration and discrimination in the two cohorts. Calibration curves were plotted, and survival probabilities were compared. Finally, to quantify the discrimination power, we estimated the concordance index (C-index)., Results: In the upfront hepatectomy group, the C-index was 0.63, the suitable cutoff value of the Beppu score was 7, and adjuvant chemotherapy was significantly effective limited to high-risk patients (Beppu score ≥7). The C-index was 0.56 in the preoperative chemotherapy group., Conclusions: The JSHBPS nomogram remains beneficial for patients undergoing upfront hepatectomy in the recent era but is less effective for patients undergoing hepatectomy after chemotherapy. Patients with a Beppu score ≥7 showed high-risk recurrence, and adjuvant chemotherapy should be recommended for these patients., (© 2022 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

We investigated the clinical features of bloodstream infections (BSIs) caused by Klebsiella pneumoniae harboring rmpA and molecular characteristics of the bacteria. We retrospectively investigated adult patients with K. pneumoniae BSI from January 2010 to March 2021 at Nagasaki University Hospital. A matched case-control study in a 1:3 ratio was conducted to clarify the clinical and bacterial characteristics of BSI caused by rmpA-positive K. pneumoniae compared with those caused by rmpA-negative isolates. Antimicrobial susceptibility testing and multilocus sequence typing (MLST) were performed for rmpA-positive isolates. The rmpA was detected in 36 (13.4%) of the 268 isolates. Of these 36 isolates, 31 (86.1%) harbored iucA and 35 (97.2%) each possessed peg-344 and iroB; capsular types were identified as K1 in 9 (25.0%) and K2 in 10 isolates (27.8%). Contrarily, of the 108 rmpA-negative isolates, which were matched for case-control studies, 5 isolates (4.6%) harbored iucA and 1 (0.9%) each possessed peg-344 and iroB; 2 (1.9%) and 3 isolates (2.8%) had K1 and K2 capsular types, respectively. Among the rmpA-positive isolates, ST23/K1 (eight isolates) was the most frequent, followed by ST412/non-K1/K2 (seven isolates), ST86/K2 (five isolates), and ST268/non-K1/K2 (four isolates). In a multivariate analysis using clinical factors, liver abscess positively correlated with rmpA-positive isolates, whereas biliary tract infection and use of anticancer drugs negatively correlated with rmpA-positive isolates in patients with K. pneumoniae BSI. Considering the correlation between rmpA-positive isolates and clinical features, rmpA can be used as a marker for understanding the pathophysiology of K. pneumoniae BSI., (© 2023. The Author(s).)

Objectives: The present study developed a new risk model for congenital heart surgery in Japan and determined the relationship between hospital procedural volume and mortality using the developed model., Methods: We analyzed 47,164 operations performed between 2013 and 2018 registered in the Japan Cardiovascular Surgery Database-Congenital and created a new risk model to predict the 90-day/in-hospital mortality using the Japanese congenital heart surgery mortality categories and patient characteristics. The observed/expected ratios of mortality were compared among 4 groups based on annual hospital procedural volume (group A [5539 procedures performed in 90 hospitals]: ≤50, group B [9322 procedures in 24 hospitals]: 51-100, group C [13,331 procedures in 21 hospitals]: 101-150, group D [18,972 procedures in 15 hospitals]: ≥151)., Results: The overall mortality rate was 2.64%. The new risk model using the surgical mortality category, age-weight categories, urgency, and preoperative mechanical ventilation and inotropic use achieved a c-index of 0.81. The observed/expected ratios based on the new risk model were 1.37 (95% confidence interval, 1.18-1.58), 1.21 (1.08-1.33), 1.04 (0.94-1.14), and 0.78 (0.71-0.86) in groups A, B, C, and D, respectively. In the per-procedure analysis, the observed/expected ratios of the Rastelli, coarctation complex repair, and arterial switch procedures in group A were all more than 3.0., Conclusions: The risk-adjusted mortality rate for low-volume hospitals was high for not only high-risk but also medium-risk procedures. Although the overall mortality rate for congenital heart surgeries is low in Japan, the observed volume-mortality relationship suggests potential for improvement in surgical outcomes., (Copyright © 2022 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been widely used for critically ill patients all over the world; however, comprehensive survey regarding the relationship between VA-ECMO duration and prognosis is limited. We conducted a survey of VA-ECMO patients in the Japanese Registry of All Cardiac and Vascular Diseases-Diagnosis Procedure Combination (JROAD-DPC), which was a health insurance claim database study among cardiovascular centers associated with the Japan Circulation Society, between April 2012 and March 2016. Out of 13,542 VA-ECMO patients, we analyzed 5766 cardiovascular patients treated with VA-ECMO. 68% patients used VA-ECMO only for 1 day and 93% had VA-ECMO terminated within 1 week. In multivariate analysis, the hazard ratio of 1-day support was significantly high at 1.72 (95% confidence intervals; 95% CI 1.53-1.95) (p < 0.001), while that of 2-day [0.60 (95% CI 0.49-0.73)], 3-day [0.75 (95% CI 0.60-0.94)], 4-day [0.43 (95% CI 0.31-0.60)] and 5-day support [0.62 (95% CI 0.44-0.86)] was significantly low. Comprehensive database analysis of JROAD-DPC revealed that cardiovascular patients who were supported with VA-ECMO for 2-5 days showed lower mortality. The optimal VA-ECMO support window should be investigated in further studies., (© 2022. Springer Japan KK, part of Springer Nature.)

Background: Dengue fever is a viral infection transmitted to humans through the bite of a mosquito infected with the dengue virus. Dengue is one of the most common infectious diseases in the world, and its incidence is rapidly increasing. We estimated the risk of dengue importation from endemic countries to Japan and the transmission risk within Japan using data collected between 2016 and 2018., Methods: We conducted simulations that included the number of reported dengue infections and travelers per month in ten countries in Southeast and South Asia., Results: The estimated importation risks for Japanese returnees and international travelers from each of the ten endemic countries was approximately 1.0 every month from 2016 to 2018. The autochthonous transmission risk in Japan from any target country was 1.0 from June to September yearly. The estimated number of Japanese dengue cases returning to Japan is approximately 25 times higher than that of imported cases reported in Japan., Conclusions: The risk of dengue importation into Japan can be sufficiently high. Attention should be paid to autochthonous transmission spread between June and September when mosquitoes are active in Japan. Estimates of seasonal risk variation from each dengue virus-endemic country can be used to inform preventive and control measures for dengue in Japan.

Background: Hepatitis B virus (HBV) is one of the most prevalent chronic viral infections that causes chronic hepatitis B (CHB). In Japan, genotypes B and C account for most of acute and chronic cases of hepatitis. However, previous studies showed that the prevalence of genotype A in CHB gradually increased every 5 years. Therefore, we have conducted a nationwide survey to comprehensively investigate the trends of HBV genotype distribution in CHB patients in Japan., Methods: 4421 CHB patients were recruited between 2015 and 2016. Clinical characteristics and distribution of CHB patients among different age groups and genotypes in 2015-2016 was compared with those in 2000-2001, 2005-2006, and 2010-2011., Results: The percentages of genotype A, B, C, and D were 4.0, 16.2, 79.1, and 0.7%, respectively. While the overall percentage of CHB patients with genotype A did not change in the past 5 years, CHB with genotype A increased in young adults. On the other hand, the peak distribution of CHB with genotypes B and C, two genotypes with the largest patient population, has shifted to an older age group., Conclusions: In Japan, the peak distribution for CHB with genotypes B and C advanced to an older age group while CHB with genotype A expanded in a younger age group. Given the universal HBV vaccination launch in Japan in 2016, these pre-vaccination survey data provide important baseline information for comparative studies of the impact of universal vaccination on HBV genotypes., (© 2022. Japanese Society of Gastroenterology.)

Objectives: Complete atrioventricular septal defect with tetralogy of Fallot is a rare and complex heart disease. This study aimed to describe contemporary management approaches for this heart disease and the outcomes., Methods: Data were obtained from 46 domestic institutions in the Japan Cardiovascular Database (2011-2018). Patients with a fundamental diagnosis of complete atrioventricular septal defect with tetralogy of Fallot, without other complex heart diseases, were included. The primary outcome was operative mortality (30-day or in-hospital mortality)., Results: A total of 119 patients underwent initial surgery for a complete atrioventricular septal defect with tetralogy of Fallot during this study period. Primary repair was performed in 40 (34%) patients (primary repair group), and palliative procedure was performed in 79 (66%) patients as part of a planned staged approach (staged group). Forty institutions (87%) experienced at least one case of staged repair. No institution experienced more than or equal to two cases/year on average during the study period. Overall, 11 operative mortalities occurred (9.2%). Operative mortality rates in the primary and staged groups were comparable (p = 0.5). Preoperative catecholamine use, repeat palliative surgeries, and emergency admission were significant risk factors for operative mortality in multivariate analysis (odds ratio, 95% confidence interval: 8.58, [0-0.11]; 12.65, [1.28-125.15]; 8.64, [1.87-39.32, respectively])., Conclusions: Staged approach for complete atrioventricular septal defect with tetralogy of Fallot was the preferred option. The outcomes of this complex disease were favorable for patients in centers with low cases of complete atrioventricular septal defect with tetralogy of Fallot., (© 2022. The Author(s), under exclusive licence to The Japanese Association for Thoracic Surgery.)

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).)

Background: Regorafenib significantly improves overall survival in previously treated metastatic colorectal cancer patients. However, various toxicities, such as hand-foot skin reaction (HFSR), fatigue, and liver dysfunction have limited the use of regorafenib. These toxicities appear soon after treatment initiation. The ReDOS study demonstrated the effectiveness of a weekly dose-escalation therapy of regorafenib starting with a lower daily dose; however, its usefulness in Asian subjects is unknown. We conducted a phase II study to evaluate the safety and survival benefit of regorafenib dose-escalation therapy for Japanese patients., Methods: Patients with sufficient organ function, who had previously received more than two lines of chemotherapy were included. Regorafenib was started at 80 mg/day and escalated to 120 mg/day in Week 2 and 160 mg/day in Week 3, if no severe drug-related toxicities were observed. The primary endpoint was cancer progression-free survival (PFS). Tumor response and progression were assessed radiologically every 8 weeks. This study was registered in the University Hospital Medical Information Network (UMIN#UMIN000028933)., Results: 57 patients were enrolled and all started regorafenib at 80 mg/day. 32 patients (56.1%) were subsequently escalated to 120 mg/day and 19 (33.3%) to 160 mg/day. Only 8 patients (14.0%) discontinued treatment because of adverse events. Median PFS was 1.9 months. Median overall survival was 8.9 months, the response rate was 0%, and the disease control rate was 31.6%. The most frequent adverse event greater than grade 3 was hypertension (19.3%), followed by HFSR (14.0%)., Conclusions: Regorafenib dose-escalation therapy is well tolerated with PFS-like regorafenib standard therapy., (© 2022. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Anal canal cancer (ACC) has been reported to be an uncommon cancer in Japan, as in the USA, Europe, and Australia. This retrospective multi-institutional study was conducted to clarify the characteristics of ACC in Japan. First, the histological ACC type cases treated between 1991 and 2015 were collected. A detailed analysis of the characteristics of anal canal squamous cell carcinoma (SCC) cases was then conducted. The results of the histological types revealed that of the 1781 ACC cases, 435 cases (24.4%) including seven cases of adenosquamous cell carcinomas were SCC and 1260 cases (70.7%) were adenocarcinoma. However, the most common histological type reported in the USA, Europe, and Australia is SCC. Most ACC cases are adenocarcinomas and there is a low incidence of SCC in Japan which is different from the above-mentioned countries. Moreover, we reclassified T4 into the following two groups based on tumor size: T4a (tumor diameter of 5 cm or less) and T4b (tumor diameter of more than 5 cm). The results of the TNM classification of SCC revealed that the hazard ratio (HR) to T1 of T2, T3, T4a, and T4b was 2.45, 2.28, 2.89, and 4.97, respectively. As T4b cases had a worse prognosis than T4a cases, we propose that T4 for anal canal SCC in Japan be subclassified into T4a and T4b., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Cardiovascular and cerebrovascular diseases are considered the principal cause of morbidity and mortality worldwide; the effect of stroke-induced cardiac manifestations is well recognized; however, not enough clinical data have been found about the impact of stroke with underlying cardiac disease. This study's objective is to assess the impact of stroke on the prognosis of patients with underlying IHD, who underwent PCI treatment. This was a multicenter, 1-year observational study in patients undergoing PCI in one of the 17 participating centers across Japan. 18,495 patients were registered on the PCI list; 2481 patients had a prior stroke experience, whereas 15,979 were stroke-free. Our study revealed that stroke patients were significantly older (mean age 73.5 ± 9.6, 69.7(± 11.5), respectively), and suffered from more comorbidities (diabetes, hypertension, and chronic kidney disease, p < 0.0001). During the 1-year period, subjects with stroke showed higher incidence of clinical events compared to those without stroke; to illustrate, all-cause death accounted for 6.2% in patients with stroke, in contrast to only 2.8% in stroke-free patients (p < 0.0001), cardiac death amounted for 2.2 and 1.2%, respectively (p < 0.0001), recurrent stroke for 3.1% and 1.2% (p < 0.0001), non-cardiac death for 3.6 and 1.54% (p < 0.0001), and finally, hemorrhagic complications with 2.6 and 1.3% (p < 0.0001). Kaplan-Meier analysis revealed that stroke patients had a higher probability of all-cause mortality, cardiac death, and recurrent stroke (log-rank p < 0.0001). Cox hazard analysis also showed that the presence of stroke is a significant indicator in determining the outcome of cardiac death (HR = 1.457, 95% CI 1.036-2.051, p = 0.031); hence, proving it to be a crucial predictor on cardiac prognosis. History of prior stroke was common in PCI patients, and independently associated with a higher rate of subsequent cardiovascular and cerebrovascular events recurrence. Thus, highlighting an urgent need for comprehensive prevention of cardiac and cerebrovascular diseases., (© 2021. Springer Japan KK, part of Springer Nature.)

We report the efficacy of a Japanese fracture liaison service (FLS), the osteoporosis liaison service (OLS), in suppressing osteoporosis-related expenses from the public insurance by preventing secondary fracture in spite of higher medication costs during expected life spans. OLS could reduce medical expenses for osteoporosis in all age groups., Purpose: Osteoporosis liaison services (OLS), which are based on fracture liaison services (FLS), are used in Japan to prevent both primary and secondary fractures in older people. We aimed to clarify the effects of OLS on the medical expenses., Patients and Methods: We compared patients with fragile fractures hospitalized to Saitama Jikei Hospital before and after implementing OLS. These were labeled a non-OLS group and an OLS group, and they were further organized by age (< 75, 75-84, and ≥ 85 years). The expected osteoporosis-related medical expenses during life were calculated by the occurrence, fracture site, medication, and life expectancy and compared between the non-OLS and OLS groups by the age group., Results: The non-OLS group included 400 people (100 males and 300 females, mean age 81.7 ± 9.7 years), comprising 154 with vertebral fractures and 246 with hip fractures. The OLS group included 406 patients (101 males and 305 females, mean age 82.4 ± 9.3 years), of whom 161 had vertebral fractures and 245 had hip fractures. The suppressive secondary fracture effects of OLS were previously reported. The expected expense of osteoporosis treatment in the OLS group was found to be greater than that in the non-OLS group for all age groups. In contrast, expected expenses for treating secondary fractures were shown to increase more in the non-OLS group. However, total expenses were lower in the OLS group across all age groups., Conclusion: The implementation of OLS can reduce overall healthcare costs despite the increased expenses required to provide medical therapy and periodic examinations., (© 2022. International Osteoporosis Foundation and National Osteoporosis Foundation.)

Background: The efficacy of adjuvant chemotherapy for high-risk stage II colon cancer (CC) has not been well established. We compared the effects of surgery with and without oral uracil and tegafur plus leucovorin (UFT/LV) in patients with high-risk stage II CC, adjusting for potential risk factors., Methods: We enrolled patients with histologically confirmed stage II colon adenocarcinoma with at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes. Patients chose to be non-randomized or randomized to undergo surgery alone (NR-Group S or R-Group S) or surgery followed by 6 months of UFT/LV (NR-Group U or R-Group U). The primary endpoint was disease-free survival (DFS) after adjusting for previously reported risk factors using propensity score matching (1:2) and inverse probability of treatment weighting (IPTW) in the non-randomized arm., Results: Overall, 1,902 (98%) and 36 (2%) patients were enrolled in the non-randomized and randomized arms, respectively. There were too few patients in the randomized arm and these were therefore excluded from the analysis. Of the 1,902 patients, 402 in NR-Group S and 804 in NR-Group U were propensity score-matched. The 3-year DFS rate (95% confidence interval) was significantly higher in NR-Group U (80.9% [77.9%-83.4%]) than in NR-Group S (74.0% [69.3%-78.0%]) (hazard ratio, 0.64 [0.50-0.83]; P = 0.0006). The 3-year overall survival rate was not significantly different between NR-Group S and NR-Group U. Significantly higher 3-year DFS (P = 0.0013) and overall survival (P = 0.0315) rates were observed in NR-Group U compared with NR-Group S using IPTW., Conclusions: Adjuvant chemotherapy with UFT/LV showed a significant survival benefit over surgery alone in patients with high-risk stage II CC characterized by at least one of the following conditions: T4 disease, perforation/penetration, poorly differentiated adenocarcinoma/mucinous carcinoma, or < 12 dissected lymph nodes., Trial Registration: Japan Registry of Clinical Trials: jRCTs031180155 (date of registration: 25/02/2019) (UMIN Clinical Trials Registry: UMIN000007783 , date of registration: 18/04/2012)., (© 2022. The Author(s).)

Aim: Matrix metalloproteinases (MMPs) play critical roles in acute myocardial infarction (AMI). This trial was conducted to determine the potential effects of higher-dose rosuvastatin on circulating MMP levels in patients with AMI., Methods: This was a multicenter, open-label, 1:1 randomized, parallel-group study. Patients with AMI were randomly assigned to the appropriate-dose group (10 mg rosuvastatin once daily) or the low-dose group (2.5 mg rosuvastatin once daily) within 24 hours after percutaneous coronary intervention. MMP-2 and MMP-9 levels were measured on day 1 and at week 4, 12, and 24 after enrollment. The primary endpoint was the change in MMP levels at 24 weeks after enrollment. The secondary endpoints were change in MMP levels at day 1 and weeks 4 and 12 after enrollment., Results: Between August 2017 and October 2018, 120 patients with AMI from 19 institutions were randomly assigned to either the appropriate-dose or the low-dose group. There were 109 patients who completed the 24-week follow-up. The primary endpoint for both MMP-2 and MMP-9 was not significantly different between the two groups. The change in the active/total ratio of MMP-9 at week 12 after baseline was significantly lower in the appropriate-dose group compared with the low-dose group (0.81 [-52.8-60.1]% vs. 70.1 [-14.5-214.2]%, P=0.004), while the changes in MMP-2 were not significantly different between the two groups during the study period., Conclusions: This study could not demonstrate the superiority of appropriate-dose of rosuvastatin in inhibiting serum MMPs levels in patients with AMI.

For indirect determination of 3-chloro-1,2-propanediol fatty acid esters (3-MCPDEs) and glycidyl fatty acid esters (GEs) in thermally processed foodstuffs distributed in Japan, we modified two published methods, an enzymatic method (later approved as JOCS Standard Method for the Analysis of Fats, Oils, and Related Materials 2.4.14 -2016 and Joint JOCS/AOCS Official Method Cd 29d-19) and EFSA method developed by the Joint Research Centre of the European Commission. The performance of these methods was demonstrated to be satisfactory. The partially modified enzymatic method showed mean recoveries of 93.7-98.5% for 3-MCPDEs, 94.4-98.4% for GEs, and HorRat (r) values of 0.06-0.78 in analyses of 6 types of foods including Japanese specific foods (fried rice cracker, fried instant noodle, biscuit, karinto, vegetable tempura, and frozen deep-fried chicken) spiked with 3-MCPD dioleate and glycidyl oleate at 0.02-0.04 mg/kg or 0.2-0.4 mg/kg. The partially modified EFSA method showed mean recoveries of 96.6-99.4% for 3-MCPDEs, 95.7-100.1% for GEs, and HorRat (r) values of 0.14-1.05 in analyses of 5 types of foods (not including karinto) spiked simultaneously with 3-MCPD dioleate and glycidyl oleate at either 0.02-0.04 mg/kg or 0.2-0.4 mg/kg. The results of analyses of 9 samples (fried rice cracker, biscuit, 2 potato crisps, fried potato snack, baked cracker, cracker dough, seafood tempura, and frozen deep-fried chicken) using these 2 methods were comparable. The 95% confidence intervals determined with weighted Deming regression analysis between the results of 3-MCPDEs or GEs in the same samples analyzed by the 2 methods showed: the slope around 1 (3-MCPDEs, 0.982-1.025; GEs, 0.887-1.078); and intercept close to 0 (3-MCPDEs, －0.002-0.003; GEs, －0.011-0.015). These data confirmed that the concentrations of 3-MCPDEs and GEs in food samples determined by 2 independent analytical methods were equivalent.

Background: The plasmid-mediated bacterial colistin-resistant gene, mcr, is of global concern in clinical healthcare. However, there are few reports of surveillance for mcr in Japan. The aim of this study was to assess the prevalence of colistin resistance by identifying nine mcr genes in extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae and carbapenem-resistant Enterobacteriaceae (CRE) isolates in Japan., Methods: A total of 273 ESBL and CRE clinical isolates were collected from patients in five tertiary hospitals from August 2016 to March 2017. Minimum inhibitory concentration (MIC) of colistin was measured using the microdilution method. Polymerase chain reaction (PCR) was performed to detect mcr-1 to mcr-9 genes in all strains. Whole-genome sequencing (WGS) analysis was conducted for any mcr-genes identified that had not been previously reported in patients from Japan., Results: The rate of colistin resistance was 7.7% in all strains, with a higher rate in the CRE strains than in the ESBL-producing strains (20.4% versus 1.1%). The mcr-5 and mcr-9 gene were detected in one ESBL-producing Escherichia coli strain (1/273, 0.37%) and three CRE strains (3/273, 1.1%), respectively. As the ESBL-producing E. coli strain was the first clinical strain with mcr-5 in Japan, WGS analysis was performed for the strain. The sequence type of the mcr-5-positive strain was ST1642 and it carried two distinct plasmids, ESBL gene-carrying pN-ES-6-1, and mcr-5.1-carrying pN-ES-6-2., Conclusions: The results of this study showed that the frequency of colistin resistance and mcr-positive strains is not high in Japan. As the MIC for colistin was low in the mcr-5.1 and mcr-9 gene-positive strain, continuous monitoring of mcr genes is necessary., Competing Interests: Declaration of Competing Interests All authors: No reported conflicts of interest., (Copyright © 2021 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.)

Percutaneous coronary intervention (PCI) has significantly advanced over the last 40 years, but it is not clear whether there have been any changes in prognosis in recent years. The Kumamoto Intervention Conference Study Real-World Registry is a multi-center registry that enrolls consecutive patients undergoing PCI in 17 centers in Kyushu, Japan. To elucidate the clinical impact of recent changes in treatment strategies, 8841 consecutive participants (historical PCI: n = 4038, enrolled between January 2013 and December 2014, and current PCI: n = 4803, between January 2015 and March 2017) with 1-year follow-up data were analyzed. The incidences of major adverse cardiovascular and other clinical events were comparable between historical PCI and current PCI, even though complex lesions were more frequent during the more recent period. During this period, the use of radial approaches, drug eluting stents, and coronary imaging was greater. The use of prasugrel was more frequent (P < 0.001) during the time periods. Comparable event rates were associated with the use of clopidogrel (52.7%) and prasugrel (47.3%). In the sub-analysis for acute coronary syndrome (n = 5047), similar clinical event rates were recorded for historical and current PCI. Although the lesions to be treated are becoming more severe and complex, equivalent clinical outcomes have been maintained in recent years, possibly due to advances in the devices and medication used., (© 2021. Japanese Association of Cardiovascular Intervention and Therapeutics.)

Objectives: We elucidate to investigate the prevalence of and factors associated with the use of physical restraints among critically ill or injured children in PICUs., Design: This was a multicenter, longitudinal point prevalence study., Setting: We included 26 PICUs in Japan., Patients: Included children were 1 month to 10 years old. We screened all admitted patients in the PICUs on three study dates (in March, June, and September 2019)., Intervention: None., Measurements and Main Results: We collected prevalence and demographic characteristics of critically ill or injured children with physical restraints, as well as details of physical restraints, including indications and treatments provided. A total of 398 children were screened in the participating PICUs on the three data collection dates. The prevalence of children with physical restraints was 53% (211/398). Wrist restraint bands were the most frequently used means (55%, 117/211) for potential contingent events. The adjusted odds of using physical restraint in patients 1-2 years old was 2.3 (95% CI, 1.3-4.0) compared with children less than 1 year old. When looking at the individual hospital effect, units without a prespecified practice policy for physical restraints management or those with more than 10 beds were more likely to use physical restraints., Conclusions: The prevalence of physical restraints in critically ill or injured children was high, and significant variation was observed among PICUs. Our study findings suggested that patient age, unit size, and practice policy of physical restraint could be associated with more frequent use of physical restraints., Competing Interests: The authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: The high mortality of acute myocardial infarction (AMI) with cardiogenic shock (i.e., Killip class IV AMI) remains a challenge in emergency cardiovascular care. This study aimed to examine institutional factors, including the number of JCS board-certified members, that are independently associated with the prognosis of Killip class IV AMI patients., Methods and results: In the Japanese registry of all cardiac and vascular diseases-diagnosis procedure combination (JROAD-DPC) database (years 2012-2016), the 30-day mortality of Killip class IV AMI patients (n=21,823) was 42.3%. Multivariate analysis identified age, female sex, admission by ambulance, deep coma, and cardiac arrest as patient factors that were independently associated with higher 30-day mortality, and the numbers of JCS board-certified members and of intra-aortic balloon pumping (IABP) cases per year as institutional factors that were independently associated with lower mortality in Killip class IV patients, although IABP was associated with higher mortality in Killip classes I-III patients. Among hospitals with the highest quartile (≥9 JCS board-certified members), the 30-day mortality of Killip class IV patients was 37.4%., Conclusions: A higher numbers of JCS board-certified members was associated with better survival of Killip class IV AMI patients. This finding may provide a clue to optimizing local emergency medical services for better management of AMI patients in Japan.

Background: The coronavirus disease (COVID-19) has afflicted large populations worldwide. Although vaccines aroused great expectations, their side effects on Japanese people and the antibody titer transition after vaccination are unclear., Methods: The side effects of the BNT162b2 mRNA COVID-19 vaccine in participants who received vaccination at our center were investigated. Some participants were also surveyed for the antibody titer transition., Results: In this study, 983 and 798 Japanese participants responded to the first and second doses, respectively. Side effects occurred in 757 (77.0%) and 715 participants (90.0%) after the first and second doses, respectively. No Grade 4 side effects occurred. The second dose had significantly more side effects than the first dose (p < 0.001). Side effects occurred after the second dose in 571 female (92.1%) and 178 male participants (80.1%). Female participants had a higher incidence of side effects than the male participants (p < 0.001). A comparison among the age groups showed significant differences (p = 0.018), and the frequency of side effects decreased with age. Twenty-three individuals participated in the survey of antibody titer transition. After the second vaccine dose, the median antibody titers for IgG and IgM were 3.76 and 0.07 AU/mL, respectively. Both IgG and IgM titers showed a significant increase over the study period (p < 0.001)., Conclusions: The BNT162b2 mRNA COVID-19 vaccine might be safe for Japanese people, and the antibody titer increased with two doses of vaccination. Larger nationwide studies are warranted to verify these findings., Competing Interests: Conflict of Interest The authors have no conflicts of interest to declare regarding this study., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background and Objectives: Red yeast rice contains monacolin K, an inhibitor of cholesterol synthesis, and gamma-aminobutyric acid, a neurotransmitter. The daily dose of red yeast rice and monacolin K in previous studies was relatively high; therefore, there were safety concerns. We aimed to examine the effects of low daily dose red yeast rice on arteriosclerosis in patients with mild dyslipidemia., Methods and Study Design: Eighteen patients without known cardiovascular disease and unsatisfactory low-density lipoprotein cholesterol (3.96±0.19 mmol/L) controlled only by diet therapy were randomly allocated to receive low dose red yeast rice (200 mg/day) containing 2 mg monacolin K or diet therapy alone for 8 weeks. The primary outcome was the absolute change in low-density lipoprotein cholesterol. Secondary outcomes included total cholesterol, apolipoprotein B, and blood pressure., Results: Low-density lipoprotein cholesterol decreased significantly in the red yeast rice group than in the diet therapy group (median [interquartile range]: control -0.20 [-0.62, 1.19] mmol/L vs. red yeast rice -0.96 [-1.05, -0.34] mmol/L, p=0.030). The red yeast rice group also exhibited significant decreases in total cholesterol, apolipoprotein B, and blood pressure. No severe treatment-related adverse effects on muscles, liver, or renal function were observed., Conclusions: We found that patients in the red yeast rice group exhibited significant reductions in lowdensity lipoprotein cholesterol, total cholesterol, apolipoprotein B, and blood pressure without any recognised adverse effect. This suggests that low daily dose red yeast rice could reduce cardiovascular risk in patients with dyslipidemia.

Background: The spinal accessory nerve (SAN) has several anatomical variations, which may be a pitfall in neck dissection (ND). These include the trapezius muscle branch (TB), which stems from the common trunk before entering the sternocleidomastoid muscle (SCM)., Aims/objectives: To investigate the prevalence of this variation and suggest a protocol for preventing unexpected injury of the TB in ND., Materials and Methods: We conducted a retrospective cohort study for 93 patients who had undergone neck dissection (117 sides) without resection of the SCM nor SAN. We recorded the division of the TB after and before penetration of the SCM by the common trunk (penetrating type TB [PTB]) and non-penetrating type TB [NPTB], respectively)., Results: Among NDs, PTB and NPTB were observed in 61 (52%) and 56 (48%) sides, respectively. In the subgroup of 24 cases with bilateral ND, PTB/PTB, NPTB/NPTB, and NPTB/PTB were observed in eight (33%), nine (38%), and seven (29%) cases, respectively. The prevalence of PTB/NPTB did not differ according to age, sex, or laterality., Conclusions and Significance: NPTB is a common anatomical variation. The presence or absence of a branch from the common trunk must be initially checked to avoid unexpected damage to the TB.

Objectives: To reveal the mid-term outcomes of Contegra implantation for the reconstruction of the right ventricular outflow tract to proximal branch pulmonary arteries in a multicentre study., Methods: Between April 2013 and December 2019, 178 Contegra conduits were implanted at 5 Japanese institutes. The median age and body weight at operation were 16 months (25th-75th percentile: 8-32) and 8.3 kg (6.4-10.6). Sixteen patients were neonates (9.0%). Selected conduit sizes were 12 mm in 28 patients (15.7%), 14 mm in 67 patients (37.6%), 16 mm in 66 patients (37.1%), 18 mm in 5 patients (2.8%) and <12 mm in 12 patients (6.7%). Fifty-six grafts (31.4%) were ring supported. Proximal branch pulmonary arteries were concomitantly augmented in 85 patients (47.5%). Follow-up was completed in all patients and the median follow-up period was 3.1 years (1.3-5.1)., Results: The overall, conduit explantation-free and conduit infection-free survival rates at 5 years were 91.3%, 71.0% and 83.7%, respectively. Infection (P = 0.009) and common arterial trunk (P = 0.024) were risk factors for explantation. Conduit durability was shorter in smaller one (P < 0.001). Catheter interventions (for conduit to proximal branch pulmonary artery)-free survival rates at 5 years was 52.9%; however, need for catheter interventions was not a risk factor for conduit explantation., Conclusions: Mid-term outcomes of reconstruction of the right ventricular outflow tract to the proximal branch pulmonary arteries with Contegra were acceptable. The need for explantation over time was higher in smaller conduits. Conduit infection was a strong risk factor for conduit explantation. Frequently and repeated catheter interventions effectively extended the conduit durability., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Though nonalcoholic fatty liver disease (NAFLD) is related to chronic kidney disease (CKD), it is unclear whether the hepatic steatosis index (HSI), a screening tool for NAFLD, is related to CKD. The present study investigated the relationship between HSI and CKD among middle-aged individuals in Japan., Methods: Subjects were adults (aged 40-64 years) who received an annual health checkup in Japan between April 2013 and March 2014. Height and weight were measured, and venous blood samples were obtained to determine alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine levels. HSI was calculated by the following formula: HSI = 8 × ALT/AST ratio + body mass index (+2, if diabetes; +2, if female). CKD was defined as an estimated glomerular filtration rate < 60 mL/min/1.73 m 2 and/or urinary protein of ≥ (+). Logistic regression analysis was performed to estimate the odds ratio (OR) and its 95% confidence interval (CI) for CKD., Results: Data of 94,893 adults were analyzed. Compared with men with an HSI < 30, men with 30 ≤ HSI ≤ 36 (OR: 1.50, 95% CI: 1.40-1.61) and HSI > 36 (OR: 2.14, 95% CI: 1.99-2.31) had significantly higher ORs for CKD. Moreover, there was a significant dose-response relationship between HSI and CKD ( P for trend < 0.001). Even after adjusting for confounders, the significant results persisted. These findings in men were similar to those in women., Conclusions: This study showed that the HSI was associated with CKD among middle-aged adults in Japan. Additionally, a dose-response relationship of HSI to CKD was observed. The present study suggested that it might be useful to monitor the HSI among middle-aged individuals to detect CKD at an early stage., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2021 Hirotaka Ochiai et al.)