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Two European phase III trials comparing D1 and D2 demonstrated that D2 did not improve the overall survival and was associated with a high mortality related to splenectomy. However, a long-term follow-up study showed that the gastric cancer-related death rate was significantly higher in D1 than D2. Based on these findings, the standard surgery in Europe became D2 without pancreatico-splenectomy to prevent mortality. In contrast, the JCOG9501 phase III comparing D2 and D2 plus para-aortic nodal dissection did not showed a survival efficacy of extended lymphadenectomy, but the mortality rate was quite low in both surgeries. Subsequently, the JCOG0110 phase III study comparing D2 and spleen-preserving D2 for upper gastric cancer not invading the greater curvature clearly showed the non-inferiority of spleen preservation. Thus, spleen-preserving D2 was made the standard surgery for these tumors in Japan. However, splenectomy is often selected for complete dissection of the splenic-hilar nodes, a frequent metastatic site for upper gastric tumors invading the greater curvature. Recently, an approach involving splenic hilar nodal dissection without splenectomy has been developed. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to examine the impact of the combination of physical frailty and social isolation on falling in community-dwelling older adults. Design: A cross-sectional study of data obtained at registration in a randomized control trial. Setting: Community-based study of participants recruited from Toyota, Japan. Participants: 380 community-dwelling older adults (47.9% women, mean age = 72.3 ± 4.6 years). Measurements: Participants were categorized as non-frail or pre-frail/frail based on the Fried frailty criteria (slowness, weakness, exhaustion, low activity, and weight loss). Social isolation was examined using the Lubben Social Network Scale (LSNS-6), and scores lower than 12 points indicated social isolation. Participants were divided into four groups depending on pre-frail/frail status and social isolation, and experiences of multiple falls over the past year were compared between the groups. Results: Participants were classified into robust (n = 193), physical frailty (PF; n = 108), social isolation (SI; n = 43), and PF with SI (PF+SI; n = 36) groups. A total of 38 (10.0%) participants reported multiple falls. Logistic regression analysis showed that PF and SI groups were not independently associated with falling (PF: OR 1.64, 95% CI 0.65–4.16, SI: OR 2.25, 95% CI 0.77–6.58), while PF+SI group was significantly associated with falling compared with the robust group (OR 3.06, 95% CI 1.00–9.34, p = 0.049) after controlling for confounding factors. Conclusion: Our findings support the assertion that coexistence with physical frailty and social isolation were associated with falling in the older adults. [ABSTRACT FROM AUTHOR]

Objectives: A number of studies have reported that frailty is cross-sectionally associated with cognitive decline and is also a risk for future cognitive decline or dementia; however, there have been only a few studies that focus on the association between prefrailty and cognitive dysfunction. In the current study, we investigated the association between prefrailty and cognitionDesign: A cross-sectional study of the data obtained at registration in a randomized control trial.Setting: Toyota, Japan.Participants: Community-dwelling older subjects (male 54.6%) who had cognitive complaints.Measurements: A battery of neuropsychological and physical assessments were performed. Prefrailty was defined as exhibiting one or two of the five Fried criteria (weight loss, exhaustion, weakness, slow gait speed and low physical activity). We performed a multiple regression analysis to investigate the associations of cognitive performance with prefrailty, adjusting for the factors that were significantly different between the robust and prefrailty groups. To assess the cognitive attributes that were significantly associated with prefrailty, logistic analysis was performed to see if one specific criterion of the five frailty criteria was associated with cognitive performance.Results: The study subjects included 183 prefrail and 264 robust individuals. The prefrail subjects with cognitive complaints were older, less educated, more depressive, and more likely to have diabetes mellitus than the robust subjects. The prefrail subjects had lower performance in a wide-range of cognitive domains, and after adjustments for age, education, depressive mood, and diabetes mellitus, prefrailty was associated with a decline in delayed memory and processing speed. Among the components of the Fried criteria, slow gait speed and loss of activity were significantly associated with slow processing speed as assessed by the digit symbol substitution test.Conclusion: The current results demonstrated that prefrailty was associated with worse memory and processing speed performance, but not with other cognitive domains. [ABSTRACT FROM AUTHOR]

Study Design:This was a retrospective observational study.Objectives:The objectives were to describe the prognosis of upper extremity function following cervical spinal cord injury (CSCI), and to identify prognostic factors for functional recovery.Setting:Spinal Injuries Center, Japan.Methods:Sixty patients with C3-4 CSCI without major bone injury participated in the study. Patients were treated nonsurgically and evaluated using the American Spinal Injury Association (ASIA) scales for the upper and lower extremities, their residual cervical motor functions, the modified Frankel grade and an upper extremity function scale. We compared the findings for the upper extremity function scale at 6 months with those for the residual cervical motor functions and modified Frankel grade obtained 3 days after injury.Results:Most patients with CSCI who could flex their hip and knee from a supine position (95%) or who showed some active elbow extension (86%) 3 days after their injury could use a spoon at 6 months. We compared patients who used their fingers at 6 months to those who could not, and observed significant differences in age and ASIA scores for the upper and lower extremities obtained 3 days after injury. A strong correlation was observed between the initial motor scores and the extent of functional recovery at 6 months.Conclusion:Hip and knee flexion from the supine position and elbow extension 3 days after injury significantly predicted a positive prognosis for upper extremity function. Younger age and higher ASIA motor scores obtained 3 days after injury were factors associated with neurological recovery. [ABSTRACT FROM AUTHOR]

Background and study aims: Only a few large cohort studies have evaluated the efficacy and safety of endoscopic necrosectomy for infected walled- off pancreatic necrosis (WOPN). Therefore, a multicenter, large cohort study was conducted to evaluate the efficacy and safety of endoscopic necrosectomy and to examine the procedural details and follow-up after successful endoscopic necrosectomy. Patients and methods: A retrospective review was conducted in 16 leading Japanese institutions for patients who underwent endoscopic necrosectomy for infected WOPN between August 2005 and July 2011.The follow-up data were also reviewed to determine the long-term outcomes of the procedures. Results: Of 57 patients, 43 (75 %) experienced successful resolution after a median of 5 sessions of endoscopic necrosectomy and 21 days of treatment. Complications occurred in 19 patients (33 %) during the treatment period. Six patients died (11 %): two due to multiple organ failure and one patient each from air embolism, splenic aneurysm, hemorrhage from a Mallory-Weiss tear, and an unknown cause. Of 43 patients with successful endoscopic necrosectomy, recurrent cavity formation was observed in three patients during a median follow-up period of 27 months. Conclusions: Endoscopic necrosectomy can be an effective technique for infected WOPN and requires a relatively short treatment period. However, serious complications can arise, including death. Therefore, patients should be carefully selected, and knowledgeable, skilled, and experienced operators should perform the procedure. Further research into safer technologies is required in order to reduce the associated morbidity and mortality. [ABSTRACT FROM AUTHOR]

Gender-related risk factors in the survival of transplanted teeth with complete root formation have not yet been identified. The purpose of this study was to investigate gender differences in tooth autotransplantation at dental clinics. We asked participating dentists to provide information on transplantations they had undertaken from 1 January 1990 to 1931 December 2010. The data were screened to exclude patients who underwent more than one transplantation, smokers or those whose smoking habits were unknown, patients under 30 or who were 70 years old and over, cases where the transplanted teeth had incomplete root formation or multiple roots and those with fewer than 20 present teeth post-operation. We analysed 73 teeth of 73 males (mean age, 47·2 years) and 106 teeth of 106 females (mean age, 45·3 years) in this study. The cumulative survival rate and mean survival time were calculated using the Kaplan-Meier method. The cumulative survival rate for males was 88·3% at the 5-year mark, 64·8% at 10 years and 48·6% at 15 years; for females, it was 97·2% at the 5-year mark, 85·9% at 10 years and 85·9% at 15 years. A log-rank test indicated the difference between males and females to be significant ( P = 0·011). There was also a significant difference in the main causes for the loss of transplanted teeth: males lost more transplanted teeth due to attachment loss than females ( P < 0·05). These results indicate that males require more attention during the autotransplantation process, particularly at the stage of pre-operation evaluation and that of follow-up maintenance. [ABSTRACT FROM AUTHOR]

Interferon regulatory factor 7 (IRF7) has an essential role in the production of type I interferon. Although recent studies detected association of a single nucleotide polymorphism (SNP) rs4963128 in PHD and ring finger domains 1 (PHRF1)/KIAA1542, located closely to IRF7, and IRF7 rs1131665 (glutamine (Gln) 412 arginine (Arg)) with systemic lupus erythematosus (SLE), causal variants have not been established. In this study, we resequenced exons and introns of IRF7 to screen for all common polymorphisms, and examined whether they were associated with SLE in 416 Japanese patients with SLE and 505 healthy controls. We also tested whether the association of PHRF1 rs4963128 with SLE was replicated in a Japanese population. None of the IRF7 polymorphisms was associated with SLE. PHRF1 rs4963128T was not significantly associated with occurrence of SLE either; however, this allele was significantly increased in SLE with anti-Sm antibodies (6.8%) as compared with healthy controls (3.1%, P = 0.014, odds ratio [OR] 2.31) and SLE without anti-Sm antibodies (3.3%, P =0.041, OR 2.12). This allele was also increased in SLE with renal disorder (5.1%) as compared with those without renal disorder (2.4%, P = 0.047, OR 2.17). These results confirmed recently reported association of PHRF1 rs4963128T with anti-Sm antibody positive SLE in African-American populations, and supported the role of PHRF1-IRF7 region in the genetics of SLE. [ABSTRACT FROM AUTHOR]

Summary: Bone mineral density of the 1/3 distal radius, ultra-distal radius, and lumbar spine correlated significantly and negatively with serum adiponectin. There was a significant positive correlation between serum adiponectin and serum NTX. Thus, adiponectin may play a role in mineral and bone disorder in chronic kidney disease stage 5 dialysis (CKD 5D) patients. Introduction: Serum adiponectin, an adipocyte-produced hormone, has been reported to correlate negatively with bone mineral density (BMD) in the general population. However, little is known about the association between adiponectin and BMD in patients with CKD. Methods: BMD of the 1/3 distal and ultra-distal radius, which are enriched with cortical and cancellous bone, respectively, and the lumbar spine was measured by dual X-ray absorptiometry in 114 Japanese male hemodialysis patients (age 61.0 ± 11.1 years; hemodialysis duration 6.6 ± 3.0 years; 43.9% diabetics). Serum total adiponectin, bone formation marker (bone alkaline phosphatase, BAP), and bone resorption marker (cross-linked N-telopeptide of type I collagen (NTX)) were measured. Results: The BMD of the 1/3 distal radius, ultra-distal radius, and lumbar spine correlated significantly and negatively with serum adiponectin level ( r = −0.229, p = 0.014; r = −0.286, p = 0.002; r = −0.227, p = 0.013, respectively). In multiple linear regression analyses, serum adiponectin was significantly and independently associated with the BMD of the 1/3 distal radius ( R = 0.173, p < 0.001) and ultra-distal radius ( R = 0.278, p < 0.001) after adjustment of age, hemodialysis duration, body weight, %fat mass, and log [intact PTH], although it was not with the BMD of the lumbar spine. There was a significant positive correlation between serum adiponectin and serum NTX ( r = 0.321, p < 0.001), although there was no significant correlation between serum adiponectin and serum BAP. Conclusion: Increased levels of serum adiponectin were associated with decrease in BMD in male hemodialysis patients. Adiponectin may play a role in mineral and bone disorder, possibly in bone resorption, of patients with CKD 5D. [ABSTRACT FROM AUTHOR]

Summary The aim of this study was to investigate the usage of tooth autotransplantation in dental clinics which offer the treatment and evaluate its practicality. Participating dentists were requested to provide information on transplantations they had undertaken from 1 January 1990 to 31 December 2010. A total of 614 teeth from 552 patients (37 dentists) ranging in age from 17 to 79 (mean age: 44·1) were examined. Cumulative survival rate and mean survival time were calculated using the Kaplan-Meier method, and log rank test was used for analysis of factors. The mean number of autotransplantation patients per clinic per year was 1·4. Upper third molars constituted 36·8% of donor teeth, while 37·1% were lower third molars. The lower first molar region was the most common recipient site at 32·6%, followed by the lower second molar region (28·0%). Prosthodontic treatment of transplanted teeth involved coverage with a single crown (72·5%) and abutment of bridge (18·9%). A total of 102 transplanted teeth were lost owing to complications such as attachment loss (54·9%) and root resorption (25·7%). The cumulative survival rate in cases where donor teeth had complete root formation was 90·1% at 5 years, 70·5% at 10 years and 55·6% at 15 years. The mean survival time was 165·6 months. Older age was a significant risk factor ( P < 0·05) for survival. In cases where suitable donor teeth are available, autotransplantation of teeth may be a plausible treatment option for dealing with missing teeth in dental clinics. [ABSTRACT FROM AUTHOR]

Abstract: In an ITER facility, about 3kg of tritium will be stored in about 50 hydride beds. The safe design and operation of tritium storage beds will be one of the most important points for enhancing overall safety in the facility. In the Tritium Process Laboratory at the Japan Atomic Energy Agency, many tritium storage beds with zirconium–cobalt (ZrCo) and uranium (U) have been used with/without self-accountancy measures, and 20 years of safe handling experience has been accumulated. From this experience, the key issues to be considered for the safety design are the effects of tritium decay, such as decay heat transfer and 3He behavior, which can cause an increase in temperature and pressure in the tritide vessel, along with the normal protection against over-temperature, over-pressure and leaks in the metal-hydride bed. Concerning the safety operation, the key issues are the hydrogenation–dehydrogenation cycle sequence under the requirements of the storage system and the emergency action, such as rapid hydrogen recovery and loss of normal cooling function. [Copyright &y& Elsevier]

Abstract: At Tritium Process Laboratory (TPL) of Japan Atomic Energy Agency (JAEA), tritium technologies for a fusion reactor have been carried out up to date. The design studies of Air Detrtiation and Vent Detritiation System (ADS/VDS) of ITER have been carried out in JAEA as a contribution of Japan to ITER. For the tritium processing technologies, our efforts have been focused on the R&D of the tritium recovery system of ITER test blanket system. A ceramic proton conductor has been studied as an advanced blanket system. A series of fundamental studies on tritium safety technologies for ITER and for fusion DEMO plants has also been carried out. The main R&D activities in this field are the tritium behavior in a confinement and its barrier materials, monitoring, accountancy, detritiation and decontamination, etc. Especially, for the fundamental studies for a DEMO plants, a part of the studies will be carries out a new facility at Rokkasho in Aomori in the Broader Approach (BA) program in coming 10 years. For this purpose, a design study of the facility at Rokkasho has first been started. [Copyright &y& Elsevier]

Summary Aims To assess the impact of cigarette smoking on the incidence of Type 2 diabetes mellitus (DM) in middle-aged Japanese men. Methods The study enrolled 6250 men aged 35–60 years and free of diabetes, impaired fasting glucose and hypertension at entry. Type 2 DM was defined by a fasting plasma glucose level ≥ 7.0 mmol/l or physician-diagnosed Type 2 DM. Results Four hundred and fifty cases of Type 2 DM were confirmed during the 60 904 person-years follow-up. After adjustment for multiple covariates, including age, body mass index, alcohol consumption, physical activity, parental history of diabetes and the level of fasting plasma glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol and haematocrit, the relative risk of Type 2 DM among current smokers compared with non-smokers was 1.47 (95% confidence interval (CI) 1.14–1.92). Men who smoked > 30 cigarettes/day had a multivariate-relative risk of 1.73 (95% CI 1.20–2.48) compared with non-smokers. The number of cigarettes smoked daily and the pack-year values were positively related to the development of Type 2 DM in a dose-dependent manner (P for trends = 0.0026 and 0.001, respectively). Conclusions A cigarette smoking habit is an independent risk factor for Type 2 DM. [ABSTRACT FROM AUTHOR]

Examines manufacturing firms' restructuring behavior in the Asia-Pacific Basin and focuses on Japanese multinational enterprises (MNE) and the intrafirm division of labor between the Japanese parents and their Asian affiliates. Pattern of restructuring behavior; Time lag in the production transfer; Gaps in the stages of economic development.

Background Delayed chemotherapy-induced nausea and vomiting (CINV) is not well controlled in patients with colorectal cancer (CRC) treated with oxaliplatin (L-OHP)-based chemotherapy. Whether adding a neurokinin-1 receptor antagonist to a first-generation 5HT3 antagonist (1st-5HT3RA) and dexamethasone (DEX) is beneficial in patients on L-OHP-based chemotherapy is controversial. It is unclear whether palonosetron (PALO) or aprepitant (APR) is more effective in controlling delayed CINV. We, therefore, investigated whether PALO+DEX (PALO group) or 1st-5HT3RA+DEX+APR (APR group) was more effective in controlling delayed CINV, as well as risk factors for delayed CINV, in patients with CRC treated with L-OHP-based chemotherapy. Methods We pooled data from two prospective observational studies in Japan and one phase III clinical trial and compared the incidence of CINV between the PALO and APR groups using propensity score-matched analysis. Risk factors for CINV were identified using logistic regression models. Results Among the 404 eligible patients, those in the PALO group showed a higher incidence of delayed CINV than those in the APR group (nausea: 43.4% vs. 32.4%, P = 0.061; vomiting: 12.5% vs. 4.4%, P = 0.017). The logistic regression analysis identified alcohol consumption, motion sickness, and PALO+DEX regimen as independent risk factors for delayed nausea, and female sex and PALO+DEX regimen as those for delayed vomiting. Conclusions Treatment with the three antiemetics, including APR, was more effective in controlling delayed CINV than prophylactic treatment with the two antiemetics, including PALO. Thus, patients with CRC receiving L-OHP-based chemotherapy should be treated with three antiemetics, including APR. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, e41-e46 (2012) Abstract Aims Dehydroepiandrosterone exerts a protective effect against cardiovascular diseases. However, the relationship of dehydroepiandrosterone with the anticoagulant factor activated protein C, generated by the thrombin-thrombomodulin complex on vascular endothelial cells, remains unknown. This study aimed at studying the relationship between dehydroepiandrosterone and activated protein C generation in patients with Type 2 diabetes. Methods Sixty-two male patients with Type 2 diabetes were enrolled in this study. Data obtained from 40 healthy male subjects were used as controls. The plasma levels of dehydroepiandrosterone, the activated protein C-protein C inhibitor complex, high-sensitivity C-reactive protein and monocyte chemoattractant protein-1 were measured by enzyme immunoassays. Carotid intima-media thickness was measured by ultrasonography. Results The plasma levels of dehydroepiandrosterone (5.15 ± 2.81 vs. 3.76 ± 2.16 ng/ml; P < 0.005) and the activated protein C-protein C inhibitor complex (1.90 ± 1.07 vs. 1.02 ± 0.51 ng/ml; P < 0.001) were significantly lower in patients with diabetes than in normal subjects. Univariate analysis showed a significant correlation of the plasma level of dehydroepiandrosterone with that of the activated protein C-protein C inhibitor complex ( r = 0.48, P < 0.001), high-sensitivity C-reactive protein ( r = −0.30, P < 0.05) and with the mean intima-media thickness ( r = −0.28, P < 0.05) in patients with diabetes. Stepwise multiple regression analysis showed that the plasma level of dehydroepiandrosterone is significantly correlated with the plasma levels of the activated protein C-protein C inhibitor complex ( F = 18.06) and high-sensitivity C-reactive protein ( F = 4.94). There was no correlation between the plasma levels of dehydroepiandrosterone and monocyte chemoattractant protein-1. Conclusions These results suggest that lower circulating levels of dehydroepiandrosterone are associated with decreased activated protein C generation and higher intima-media thickness in patients with Type 2 diabetes. [ABSTRACT FROM AUTHOR]

The author reflects on the veterinary pathology in Japan. He mentions that the collaboration between the Japan College of Veterinary Pathology with the European College of Veterinary Pathology and the American College of Veterinary Pathology would enhance the standard of veterinary pathology in the field of education and research. He also states that in Japan there are two veterinary pathology organizations which is composed of the certified veterinary pathologists and the non-certified one.

Summary Background Japanese cedar (Cryptomeria japonica ) pollen is a major cause of seasonal pollinosis, and more than 10% of Japanese people suffer from this allergic disorder. However, only two major pollen allergens, Cry j 1 and Cry j 2, have been identified and exclusively characterized. Objective The aim of this study was to explore and identify important Japanese cedar pollen allergens other than Cry j 1 or Cry j 2. Methods C. japonica cDNA library was immunoscreened by rabbit antiserum raised against a partially purified cedar pollen allergen fraction. An isolated cDNA clone was inserted into a glutathione S-transferase (GST)-tagged Escherichia coli expression vector to obtain recombinant GST fusion protein. Non-fusion recombinant protein was purified by glutathione Sepharose affinity chromatography in conjunction with factor Xa cleavage of the GST moiety. IgE-binding ability of the recombinant protein was then evaluated by western blot analysis and enzyme-linked immunosorbent assay (ELISA). Results The cDNA encodes 306 amino acids with significant sequence similarity to those of plant isoflavone reductase-like proteins, which include a recently identified birch pollen allergen Bet v 5. Western blot analysis demonstrated that recombinant protein was recognized by cedar pollinosis patient IgE. In contrast to Bet v 5 being reported as a minor allergen, the recombinant protein exhibited 76% IgE binding frequency (19/25) against pollinosis patients. Conclusion Here we identified the third member of Japanese cedar pollen allergen homologous to isoflavone reductase. Its high IgE-binding frequency implicates that the isoflavone reductase homologue might be an additional major pollen allergen in C. japonica . [ABSTRACT FROM AUTHOR]

Background: Japanese (both in Japan and Hawaii) have a lower incidence of falls and of hip fracture than North American and European Caucasians, but the reasons for these differences are not clear.Subjects and Methods: A cross-sectional study. We compared neuromuscular risk factors for falls using performance-based measures (chair stand time, usual and rapid walking speed, and grip strength) among 163 Japanese women in Japan, 681 Japanese-American women in Hawaii and 9403 Caucasian women in the United States aged 65 years and over.Results: After adjusting for age, the Caucasian women required about 40% more time to complete 5 chair stands than either group of Japanese. Walking speed was about 10% slower among Caucasians than native Japanese, whereas Japanese-American women in Hawaii walked about 11% faster than native Japanese. Grip strength was greatest in Japan, which may reflect the rural farming district that this sample was drawn from. Additional adjustment for height, weight or body mass index increased the adjusted means of chair stand time and grip strength among Japanese, but the differences remained significant.Conclusions: Both native Japanese and Japanese-American women in Hawaii performed better than Caucasians on chair stand time and walking speed tests, and native Japanese had greater grip strength than Japanese in Hawaii and Caucasians. The biological implications of these differences in performance are uncertain, but may be useful in planning future comparisons between populations. [ABSTRACT FROM AUTHOR]

Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the efficacy of anti-programmed cell death 1 (anti-PD-1) antibodies in advanced AM. We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response rate (ORR, RECIST), survival estimated using Kaplan–Meier analysis, and toxicity (Common Terminology Criteria for Adverse Events 4.0.) were analyzed to estimate the efficacy of the anti-PD-1 antibodies. In total, 193 patients (nail apparatus, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 patients (74.1%). Baseline lactate dehydrogenase (LDH) was within the normal concentration in 102 patients (52.8%). The ORR of all patients was 16.6% (complete response, 3.1%; partial response, 13.5%), and the median overall survival (OS) was 18.1 months. Normal LDH concentrations showed a significantly stronger association with better OS than abnormal concentrations (median OS 24.9 versus 10.7 months; P < 0.001). Although baseline characteristics were similar between the nail apparatus and the palm and sole groups, ORR was significantly lower in the nail apparatus group [6/70 patients (8.6%) versus 26/123 patients (21.1%); P = 0.026]. Moreover, the median OS in this group was significantly poorer (12.8 versus 22.3 months; P = 0.03). Anti-PD-1 antibodies have limited efficacy in AM patients. Notably, patients with nail apparatus melanoma had poorer response and survival, making nail apparatus melanoma a strong candidate for further research on the efficacy of novel combination therapies with immune checkpoint inhibitors. • Acral melanoma is a distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. • We retrospectively examined advanced-stage acral melanoma patients treated with an anti-PD-1 antibody. • Anti-PD-1 antibodies have limited efficacy in Japanese acral melanoma patients. • Patients with nail apparatus melanoma had poorer response and survival than patients with palm and sole melanoma. [ABSTRACT FROM AUTHOR]

Background The organ donation rate in Japan is much lower than that in other developed countries for several reasons. An advanced educational program for in-hospital procurement coordinators is a possible solution for this. We introduced a Transplant Procurement Management (TPM) educational program at Hyogo Prefecture, Japan. Methods Ten healthcare professionals at Hyogo Prefecture participated in the Advanced International TPM course to educate themselves on TPM and held 2 TPM Model Organ Procurement Training Workshops at Hyogo Prefecture for in-hospital procurement coordinators. Furthermore, we held 2 workshops outside Hyogo Prefecture and at the same time undertook a pre-workshop questionnaire survey to evaluate the ability and motivation with respect to organ donation. To evaluate the effectiveness of the workshops, we conducted post-workshop and 3-months-after workshop questionnaire surveys. Results The results of the pre-workshop survey revealed that in-hospital procurement coordinators lacked the knowledge regarding the entire organ donation process, the current status of organ donation in Japan, and the definition of brain death. Moreover, they did not completely understand the meaning of “organ donation.” The results of the post-workshop questionnaire survey showed that the educational program was effective to improve the knowledge and skills of organ donation and motivated behavioral changes among the participants. Conclusions The survey results showed that our TPM model educational program offered sufficient knowledge and skills to increase organ donation at Hyogo Prefecture. We will continue this program and make an effort to further contribute to the Japanese organ donation activities. [ABSTRACT FROM AUTHOR]

Abstract: JT-60SA is a fully superconducting coil tokamak to be built under the framework of the EU-JA Broader Approach Agreement, and it aims to contribute to the complement of the ITER experiments and to the DEMO reactor design by the study of steady-state high-beta plasma experiments. The conceptual design of the JT-60SA tokamak and the peripheral systems has been carried out in close collaboration of EU and Japan from middle of 2006, and the JT-60SA Conceptual Design Report which involves an analysis of plasma physics and engineering design is summarized in May 2007. This paper intends to present an overall view of the JT-60SA project, and the latest design status of the key engineering issues such as superconducting magnets, divertor target, plasma heating devices, and magnet power supplies. [Copyright &y& Elsevier]

Background Chemotherapy-induced neutropenia (CIN) is a dose-limiting toxicity of many chemotherapy agents. Recently, CIN has been associated with longer survival time in various types of cancer, suggesting a role as a prognostic factor. However, no large-scale study has yet investigated the utility of CIN as a prognostic factor in small cell lung cancer. We therefore conducted this multicenter retrospective observational study to investigate the utility of CIN as a prognostic factor for overall survival (OS) in patients with extensive-disease small-cell lung cancer (ED-SCLC) treated with chemotherapy. Methods Clinical data, including data on CIN onset during chemotherapy, were collected from electronic medical records of patients with ED-SCLC who received standard-dose irinotecan and cisplatin (IP regimen) as primary therapy at 14 participating institutions across Japan between January 1, 2012 and December 31, 2016. Landmark analysis, with the association between OS and neutropenia as the primary endpoint was performed with 102 patients who completed all four cycles of the IP regimen and whose OS was ≥112 days. Univariate analysis using the log-rank test and multivariate analysis using the Cox proportional hazards model with factors previously identified as possible prognostic factors as covariates were also performed to examine the association between CIN and OS. Results Analysis of median OS by grade among patients who developed CIN revealed significantly longer survival in the group with grade 4 CIN (633 days, 95% confidence interval [CI]: 379–757) than in the group with grade 0 to 3 CIN (444 days, 95% CI: 360–505) (P = 0.0279). Multivariate analysis suggested that lactate dehydrogenase (LDH) of ≥ 230 IU/L (hazard ratio [HR]: 2.937; 95% CI: 1.739–4.958, P < 0.001) and grade 0 to 3 CIN (HR: 2.096; 95% CI: 1.151–3.818, P = 0.0156) are independent poor prognostic factors for ED-SCLC. Conclusions Onset of grade 4 CIN was associated with longer OS in patients with ED-SCLC. Our results also show that both LDH and CIN may be prognostic factors in patients treated using the IP regimen. Clinical trial identification This study was approved by the Institutional Review Board of our institution (approval no: T29-8-30-2-3). Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Objectives Japanese universities are required to improve both international and Japanese students' mental health, because the number of international students increases annually. Moreover, mental health data for graduate school students in Japan are lacking. Therefore, the present study attempted to examine differences in graduate school students' mental health according to major, grade, and nationality. Methods A total of 587 students from a Japanese university, which only offers graduate school education, completed the Japanese version of Kessler 6 (K6) as part of their regular health assessments; 542 students agreed to the use of their data for research purposes. Results The K6 scores were analyzed using a 3-way (major × grade × nationality) between-subjects ANOVA, and a significant second-order interaction (F(6, 518) = 2.68, p < .05) was observed. As a subsequent 2-way (major × nationality) ANOVA, performed according to grade, only showed an interaction for first-grade master's degree students (M1; F(2, 167) = 7.88, p < .01), comparisons between Japanese and international students were made according to major. For one major, Japanese students' K6 scores tended to be higher relative to those observed in international students (t(36) = 1.98, p < .10). In contrast, international students' K6 scores for another major were significantly higher than were those of Japanese students (t(86) = 3.31, p < .01). Conclusions Japanese and international M1 students' K6 scores differed significantly. University staff should take these differences into account and examine ways to support students. [ABSTRACT FROM AUTHOR]

Understanding the current situation and risk of environmental contamination by anti-influenza drugs in aquatic environments is key to prevent the unexpected emergence and spread of drug-resistant viruses. However, few reports have been focused on newer drugs that have recently been introduced in clinical settings. In this study, the behaviour of the prodrug baloxavir marboxil (BALM)-the active ingredient of Xofluza, an increasingly popular anti-influenza drug-and its pharmacologically active metabolite baloxavir (BAL) in the aquatic environment was evaluated. Additionally, their presence in urban rivers and a wastewater treatment plant (WWTP) in the Yodo River basin was investigated and compared with those of the major anti-influenza drugs used to date (favipiravir (FAV), peramivir (PER), laninamivir (LAN), and its active metabolite, laninamivir octanoate (LANO), oseltamivir (OSE), and its active metabolite, oseltamivir carboxylate (OSEC), and zanamivir (ZAN)) to comprehensively assess their environmental fate in the aquatic environment. The results clearly showed that BALM, FAV, and BAL were rapidly degraded through photolysis (2-h, 0.6-h, and 0.4-h half-lives, respectively), followed by LAN, which was gradually biodegraded (7-h half-life). In addition, BALM and BAL decreased by up to 47 % after 4 days and 34 % after 2 days of biodegradation in river water. However, the remaining conventional drugs, except for LANO (<1 % after 10 days), were persistent, being transported from the upstream to downstream sites. The LogK d values for the rates of sorption of BALM (0.5-1.6) and BAL (1.8-3.1) on river sediment were higher than those of conventional drugs (-0.5 to 1.7). Notably, all anti-influenza drugs were effectively removed by ozonation (>90-99.9 % removal) after biological treatment at a WWTP. Thus, these findings suggest the importance of introducing ozonation to reduce pollution loads in rivers and the environmental risks associated with drug-resistant viruses in aquatic environments, thereby promoting safe river environments., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cardiosphere-derived cell (CDC) infusion was associated with better clinical outcomes at 2 years in patients with single ventricle heart disease. The current study investigates time-to-event outcomes at 8 years., Methods and Results: This cohort enrolled patients with single ventricles who underwent stage 2 or stage 3 palliation from January 2011 to January 2015 at 8 centers in Japan. The primary outcomes were time-dependent CDC treatment effects on death and late complications during 8 years of follow-up, assessed by restricted mean survival time. Among 93 patients enrolled (mean age, 2.3±1.3 years; 56% men), 40 received CDC infusion. Overall survival for CDC-treated versus control patients did not differ at 8 years (hazard ratio [HR], 0.60 [95% CI, 0.21-1.77]; P =0.35). Treatment effect had nonproportional hazards for death favoring CDCs at 4 years (restricted mean survival time difference +0.33 years [95% CI, 0.01-0.66]; P =0.043). In patients with heart failure with reduced ejection fraction, CDC treatment effect on survival was greater over 8 years (restricted mean survival time difference +1.58 years [95% CI, 0.05-3.12]; P =0.043). Compared with control participants, CDC-treated patients showed lower incidences of late failure (HR, 0.45 [95% CI, 0.21-0.93]; P =0.027) and adverse events (subdistribution HR, 0.50 [95% CI, 0.27-0.94]; P =0.036) at 8 years., Conclusions: By 8 years, CDC infusion was associated with lower hazards of late failure and adverse events in single ventricle heart disease. CDC treatment effect on survival was notable by 4 years and showed a durable clinical benefit in patients with heart failure with reduced ejection fraction over 8 years., Registration: URL: https://www.clinicaltrials.gov; Unique identifiers: NCT01273857 and NCT01829750.

In this study, microplastic concentrations in the southeastern coastal regions of Japan were measured along the northward ocean current at seven stations from Okinawa to Tokai region. Concentrations ranged from 0.014 to 0.094 pieces/m 3 , except for a station near the Bungo Channel mouth, which had 0.723 pieces/m 3 . Polystyrene (PS) foam was most prevalent near the east side of Kyushu, suggesting origination from nearby coastal areas. Fragmentation levels were higher in the Tokai region. In addition, carbonyl index (CI) of polyethylene (PE) microplastics increased northward, indicating northward movement from southern regions. Standard PE microplastics showed chemical treatment does not significantly alter CI values. Further spectral analysis suggested potential oxidation of polypropylene (PP) and PS foam by chemical treatment. This study provides a comprehensive understanding of the abundance, distribution, and characteristics of microplastics in the southeastern coastal regions of Japan in the northwest Pacific, enhancing the understanding of environmental fate of microplastics., 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 © 2024 Elsevier Ltd. All rights reserved.)

Background: Chemotherapy-induced nausea and vomiting (CINV) commonly affects patient quality of life and the overall effectiveness of chemotherapy. This study aimed to evaluate whether adding neurokinin-1 receptor antagonists (NK1RAs) to 5-hydroxytryptamine-3 receptor antagonists (5-HT 3 RAs) and corticosteroids provides clinically meaningful benefits in preventing CINV in patients receiving moderately emetogenic chemotherapy (MEC)., Methods: We conducted a systematic review of PubMed, Cochrane Library, and Ichushi-Web to identify clinical studies evaluating NK1RAs combined with 5-HT 3 RAs and dexamethasone for managing CINV in MEC. The endpoints were complete response (CR), complete control (CC), total control (TC), adverse events, and costs. The data were analyzed using a random effects model., Results: From 142 articles identified, 15 randomized controlled trials (RCTs), involving 4,405 patients, were included in the meta-analysis. Approximately 60% of the patients received carboplatin (CBDCA)-based chemotherapy. The meta-analysis showed that triplet antiemetic prophylaxis with NK1RA was significantly more effective for achieving CR than doublet prophylaxis in each phase. Regarding CC, the triplet antiemetic prophylaxis was significantly more effective than the doublet in the overall (risk difference [RD]: 0.11, 95% confidence interval [CI]: 0.06-0.17) and delayed (RD: 0.08, 95% CI: 0.02-0.13) phases. For TC, no significant differences were observed in any phase. Adding NK1RA did not cause adverse events., Conclusions: Adding NK1RA to CBDCA-based chemotherapy has shown clinical benefits. However, the clinical benefits of NK1RA-containing regimens for overall MEC have not yet been established and require RCTs that exclusively evaluate MEC regimens other than CBDCA-based chemotherapy., (© 2024. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.)

Purpose: In DRLs 2020, the entrance surface air kerma (Ka,e) was set to 17 mGy/min as the reference dose rate in fluoroscopy. But, Ka,e in fluoroscopy for different regions and Ka,e in exposure was not set. A multicenter survey was conducted to evaluate Ka,e by each area., Methods: Ka,e for each area was analyzed for 79 facilities attending this survey (274 machines and 461 protocols). When the protocols were changed by the difference in disease, angiography, or IVR, the difference rate of Ka,e was evaluated. Ka,e before and after modifying the incident air kerma at the patient entrance reference point (Ka,r) and air kerma area product (P KA ) difference rate were calculated when protocols were changed, considering the DRLs 2020., Results: There were dose differences in Ka,e by each area. Compared to DRLs 2020, 36 protocols from 13 facilities modified their protocols, all of which reduced Ka,e., Conclusion: Although reducing Ka,e does not necessarily reduce Ka,r, and P KA , comparison of Ka,e by each area is expected to optimize medical exposure protection, including evaluation of quality control.

Purpose: To ascertain the characteristics of achromatopsia (ACHM) in Japan by analyzing the genetic and phenotypic features of patients with ACHM., Methods: The medical records of 52 patients from 47 Japanese families who were clinically diagnosed with ACHM were reviewed in this retrospective observational study., Results: Thirty-six causative variants of ACHM were identified in 26 families via whole-exome sequencing: PDE6C (12 families), CNGA3 (10 families), CNGB3 (two families), and GNAT2 (two families). However, none of the 6 causative variants that are known to cause ACHM, or the 275 other genes listed in RetNet, were observed in 19 families. A significant trend toward older age and worsening of ellipsoid zone disruption on optical coherence tomography images was observed (P < 0.01). Progressive ellipsoid zone disruptions were observed in 13 eyes of seven patients during the follow-up visits. These patients harbored one or more variants in PDE6C., Conclusion: The ACHM phenotype observed in this study was similar to those observed in previous reports; however, the causative gene variants differed from those in Europe. The low identification ratio of causative genes in whole-exome sequencing suggests the presence of unique hotspots in Japanese patients with ACHM that were not detectable via ordinal whole-exome sequencing.

Introduction: Comprehensive genome profiling (CGP) has revolutionized healthcare by offering personalized medicine opportunities. However, its real-world utility and impact remain incompletely understood. This study examined the extent to which CGP leads to genomically matched therapy and its effectiveness., Methods: We analyzed data from advanced solid tumor patients who underwent CGP panel between December 2019 and May 2023 at the Osaka International Cancer Institute. Patient demographics, specimen details, and expert panel assessments were collected. Turnaround time (TAT) and genomically matched therapy outcomes were analyzed. Gene alterations and their co-occurrence patterns were also assessed., Results: Among 1437 patients, 1096 results were available for analysis. The median TAT was 63 [28-182] days. There were 667 (60.9%) cases wherein recommended clinical trials were presented and there were 12 (1.1%) cases that could be enrolled in the trial and 25 (2.3%) cases that could lead to therapies under insurance reimbursement. The median progression free survival of the trial treatment was 1.58 months (95% CI: 0.66-4.37) in clinical trials and 3.66 months (95% CI: 2.14-7.13) in treatment under insurance. Pathologic germline variants were confirmed in 15 patients (1.3%). Co-alteration of CDKN2A, CDKN2B, and MTAP was significantly observed in overall population., Conclusion: The effectiveness of the genomically matched therapy based on the CGP panel was unsatisfactory. Expansion of clinical trials and utilization of remote clinical trials are required to ensure that the results of the CGP panel can be fully returned to patients., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background and Objective: Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease associated with the functional tumour suppressor genes TSC1 and TSC2 and causes structural destruction in the lungs, which could potentially increase the risk of lung cancer. However, this relationship remains unclear because of the rarity of the disease., Methods: We investigated the relative risk of developing lung cancer among patients diagnosed with LAM between 2001 and 2022 at a single high-volume centre in Japan, using data from the Japanese Cancer Registry as the reference population. Next-generation sequencing (NGS) was performed in cases where tumour samples were available., Results: Among 642 patients diagnosed with LAM (sporadic LAM, n = 557; tuberous sclerosis complex-LAM, n = 80; unclassified, n = 5), 13 (2.2%) were diagnosed with lung cancer during a median follow-up period of 5.13 years. All patients were female, 61.5% were never smokers, and the median age at lung cancer diagnosis was 53 years. Eight patients developed lung cancer after LAM diagnosis. The estimated incidence of lung cancer was 301.4 cases per 100,000 person-years, and the standardized incidence ratio was 13.6 (95% confidence interval, 6.2-21.0; p = 0.0008). Actionable genetic alterations were identified in 38.5% of the patients (EGFR: 3, ALK: 1 and ERBB2: 1). No findings suggested loss of TSC gene function in the two patients analysed by NGS., Conclusion: Our study revealed that patients diagnosed with LAM had a significantly increased risk of lung cancer. Further research is warranted to clarify the carcinogenesis of lung cancer in patients with LAM., (© 2024 Asian Pacific Society of Respirology.)

Background:  We evaluated the pharmacokinetics (PK) of low-dose (15 mg) edoxaban in very elderly patients (≥80 years) with nonvalvular atrial fibrillation (NVAF) and high bleeding risk., Methods:  This subanalysis of the phase 3, randomized, double-blind, placebo-controlled, multicenter ELDERCARE-AF study evaluated edoxaban plasma concentrations and compared them with the Japanese population of the ENGAGE AF-TIMI 48 and Japanese severe renal impairment (SRI) studies., Results:  The PK analysis population included 451 patients, 53.8% of whom concomitantly used antiplatelet drugs, 41.0% had SRI, and 38.0% had low body weight. Edoxaban plasma concentrations at trough and 1 to 3 hours post-dose in ELDERCARE-AF were 17.3 ± 13.9 ( n  = 427) and 93.3 ± 57.8 ng/mL ( n  = 447), respectively. These values were slightly higher than the 15 mg group in ENGAGE AF-TIMI 48 ( n  = 79; 12.4 ± 12.1 and n  = 115; 78.7 ± 45.0 ng/mL, respectively), lower than the ENGAGE AF-TIMI 48 high-dose reduced to 30 mg group ( n  = 83; 25.1 ± 36.6 and n  = 111; 150 ± 91.6 ng/mL, respectively), but similar to the Japanese SRI study ( n  = 39; 18.4 ± 11.2 and n  = 40; 96.8 ± 48.3 ng/mL, respectively). ELDERCARE-AF patients with SRI and low body weight (≤45 kg) had higher concentrations than those without, and those taking antiplatelet drugs had lower concentrations than those who were not., Conclusion:  PK data support edoxaban 15 mg once daily for very elderly NVAF patients with high bleeding risk, with caution for patients with SRI and/or low body weight., Competing Interests: T.Y. received personal fees from Daiichi Sankyo Co., Ltd. during the conduct of the study; grants and personal fees from Daiichi Sankyo Co., Ltd., Bayer Yakuhin, Ltd., and Bristol Myers Squibb K.K.; personal fees from Pfizer Japan Inc., Nippon Boehringer Ingelheim Co., Ltd., Ono Pharmaceutical Co., Ltd., Toa Eiyo Ltd., Novartis Pharma K.K., and Otsuka Pharmaceutical Co., Ltd. outside the submitted work. Y.I., M.F., and T.H. are employees of Daiichi Sankyo Co., Ltd. S.H. is an employee of Certara, Inc. K.O. received grants and personal fees from Daiichi Sankyo Co., Ltd. during the conduct of the study; personal fees from Daiichi Sankyo Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Bristol-Myers Squibb K.K., Medtronic Japan Co., Ltd., Johnson and Johnson K.K., and Bayer Yakuhin, Ltd. outside the submitted work., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Objective: To analyse the impact of histological discordance of subtypes (subtypes or divergent differentiation [DD]) in specimens from transurethral resection (TUR) and radical cystectomy (RC) on the outcome of the patients with bladder cancer receiving RC., Patients and Methods: We analysed data for 2570 patients from a Japanese nationwide cohort with bladder cancer treated with RC between January 2013 and December 2019 at 36 institutions. The non-urinary tract recurrence-free survival (NUTR-FS) and overall survival (OS) stratified by TUR or RC specimen histology were determined. We also elucidated the predictive factors for OS in patients with subtype/DD bladder cancer., Results: At median follow-up of 36.9 months, 835 (32.4%) patients had NUTR, and 691 (26.9%) died. No statistically significant disparities in OS or NUTR-FS were observed when TUR specimens were classified as pure-urothelial carcinoma (UC), subtypes, DD, or non-UC. Among 2449 patients diagnosed with pure-UC or subtype/DD in their TUR specimens, there was discordance between the pathological diagnosis in TUR and RC specimens. Histological subtypes in RC specimens had a significant prognostic impact. When we focused on 345 patients with subtype/DD in TUR specimens, a multivariate Cox regression analysis identified pre-RC neutrophil-lymphocyte ratio and pathological stage as independent prognostic factors for OS (P = 0.016 and P = 0.001, respectively). The presence of sarcomatoid subtype in TUR specimens and lymphovascular invasion in RC specimens had a marginal effect (P = 0.069 and P = 0.056, respectively)., Conclusion: This study demonstrated that the presence of subtype/DD in RC specimens but not in TUR specimens indicated a poor prognosis. In patients with subtype/DD in TUR specimens, pre-RC neutrophil-lymphocyte ratio and pathological stage were independent prognostic factors for OS., (© 2024 BJU International.)

Purpose: To clarify the genetic and clinical features of Japanese patients with ABCA4-associated retinopathy., Design: Retrospective, multicenter cohort study., Methods: Patients with retinal degeneration and biallelic ABCA4 variants were recruited from 13 different hospitals. Whole exome sequencing analysis was used for genetic testing. Comprehensive ophthalmic examinations were performed on matched patients. The primary outcome measure was identifying multimodal retinal imaging findings associated with disease progression., Results: This study included 63 patients: 19 with missense/missense, 23 with missense/truncation, and 21 with truncation/truncation genotypes. In total, 62 variants were identified, including 29 novel variants. Six patients had a mild phenotype characterized by foveal-sparing or preserved foveal structure, including 4 with missense/missense and 2 with missense/truncation genotypes. The p.Arg212His variant was the most frequent in patients with mild phenotypes (4/12 alleles). Clinical findings showed a disease duration-dependent worsening of the phenotypic stage. Patients with the truncation/truncation genotype exhibited rapid retinal degeneration within a few years and definite fundus autofluorescence imaging patterns, including hyper autofluorescence at the macula and few or no flecks., Conclusions: Our results indicate that missense/missense or missense/truncation genotypes, including the p.Arg212His variant, are associated with a relatively mild phenotype. In contrast, the truncation/truncation genotype causes rapid and severe retinal degeneration in Japanese patients with ABCA4-associated retinopathy. These data are vital in predicting patient prognosis, guiding genetic counseling, and stratifying patients for future clinical trials., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The Cancer and Aging Research Group (CARG) prediction tool was designed in the United States to predict grade ≥ 3 chemotherapy-related adverse events (CRAE) in older patients. However, its usefulness among Japanese people, who have different sensitivities to anticancer drugs and life expectancy, remains unknown. We aimed to prospectively evaluate the utility of the CARG tool for predicting severe CRAE in older Japanese patients with cancer., Material and Methods: Patients with solid tumors aged 65 years and older who commenced anticancer drug regimens from April 2018 to October 2020 were divided into three groups (low, medium, and high-risk) based on their CARG risk scores. Toxicity was prospectively observed by a pharmacist. The primary objective was to evaluate the correlation between the incidence of grade ≥ 3 CRAE and the CARG risk score. The secondary objective was to evaluate hematological and non-hematological toxicities. CRAE incidence was compared among the three groups using a closed testing procedure: (1) Cochran-Armitage test for trend and (2) chi-square test for paired comparison., Results: The patients (N = 165) had a median age of 71 years (range: 65-89 years). CRAE in patients divided into low-, medium-, and high-risk groups, based on CARG risk scores, were 39%, 55%, and 82%, respectively (low vs high; p < 0.001, medium vs high; p < 0.01). The incidence of severe hematologic toxicity was 37%, 35%, and 50% in the low-, medium-, and high-risk groups, respectively; the incidence of severe non-hematologic toxicity was 15%, 36%, and 65%, respectively (low vs medium; p < 0.01, low vs high; p < 0.001, and medium vs high; p < 0.01)., Discussion: To our knowledge, this is the first prospective observational study to validate the CARG prediction tool in older Japanese patients with cancer. The CARG risk score may be effective in predicting the development of non-hematologic toxicities. These results should be considered when administering chemotherapy to older Japanese patients with advanced solid tumors., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest directly relevant to the content of this article., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are now a public health concern in both community and healthcare settings worldwide. We previously identified a suspected case of a maternity clinic-centred outbreak of CA-MRSA skin infection in a regional community in Japan by PFGE-based analysis. In this study, we performed genome sequence-based analyses of 151 CA-MRSA isolates, which included not only outbreak-related isolates that we previously defined based on identical or similar PFGE patterns but also other isolates obtained during the same period in the same region. Our analysis accurately defined 133 isolates as outbreak-related isolates, collectively called the TDC clone. They belonged to a CA-MRSA lineage in clonal complex (CC) 30, known as the South West Pacific (SWP) clone. A high-resolution phylogenetic analysis of these isolates combined with their epidemiological data revealed that the TDC clone was already present and circulating in the region before the outbreak was recognized, and only the isolates belonging to two sublineages (named SL4 and SL5) were directly involved in the outbreak. Long persistence in patients/carriers and frequent intrahousehold transmission of the TDC clone were also revealed by this analysis. Moreover, by systematic analyses of the genome changes that occurred in this CA-MRSA clone during transmission in the community, we revealed that most variations were associated with mobile genetic elements (MGEs). Variant PFGE types were generated by alterations of prophages and genomic islands or insertion sequence (IS)-mediated insertion of a plasmid or a sequence of unknown origin. Dynamic changes in plasmid content, which were linked to changes in antimicrobial resistance profiles in specific isolates, were generated by frequent gain and loss of plasmids, most of which were self-transmissible or mobilizable. The introduction of IS 256 by a plasmid (named pTDC02) into sublineage SL5 led to SL5-specific amplification of IS 256, and amplified IS 256 copies were involved in some of the structural changes of chromosomes and plasmids and generated variations in the repertoire of virulence-related genes in limited isolates. These data revealed how CA-MRSA genomes change during transmission in the community and how MGEs are involved in this process.

Background: As gene-specific therapy for inherited retinal dystrophy (IRD) advances, unified variant interpretation across institutes is becoming increasingly important. This study aims to update the genetic findings of 86 retinitis pigmentosa (RP)-related genes in a large number of Japanese patients with RP by applying the standardised variant interpretation guidelines for Japanese patients with IRD (J-IRD-VI guidelines) built upon the American College of Medical Genetics and Genomics and the Association for Molecular Pathology rules, and assess the contribution of these genes in RP-allied diseases., Methods: We assessed 2325 probands with RP (n=2155, including n=1204 sequenced previously with the same sequencing panel) and allied diseases (n=170, newly analysed), including Usher syndrome, Leber congenital amaurosis and cone-rod dystrophy (CRD). Target sequencing using a panel of 86 genes was performed. The variants were interpreted according to the J-IRD-VI guidelines., Results: A total of 3564 variants were detected, of which 524 variants were interpreted as pathogenic or likely pathogenic. Among these 524 variants, 280 (53.4%) had been either undetected or interpreted as variants of unknown significance or benign variants in our earlier study of 1204 patients with RP. This led to a genetic diagnostic rate in 38.6% of patients with RP, with EYS accounting for 46.7% of the genetically solved patients, showing a 9% increase in diagnostic rate from our earlier study. The genetic diagnostic rate for patients with CRD was 28.2%, with RP-related genes significantly contributing over other allied diseases., Conclusion: A large-scale genetic analysis using the J-IRD-VI guidelines highlighted the population-specific genetic findings for Japanese patients with IRD; these findings serve as a foundation for the clinical application of gene-specific therapies., Competing Interests: Competing interests: KMN reports grants from JCR Pharmaceuticals Co, Sysmex and Novartis Pharma Co; consulting fees from Sysmex and Novartis Pharma Co; and lecture fees from Sysmex, Novartis Pharma Co and Janssen Co. KMN has patents related to gene therapy for retinitis pigmentosa. In addition, KMN is an advisory board member of Sysmex and Novartis Pharma Co., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective This longitudinal study aimed to clarify the changes in the medical treatment behavior of Japanese patients with chronic diseases during the early phase of the coronavirus disease 2019 (COVID-19) pandemic and examine the factors associated with disease worsening. Methods Subjects with chronic diseases were selected from a panel survey that started at the beginning of the COVID-19 pandemic consists of 2,400 participants recruited via the Internet. Medical treatment behaviors (decrease in medical visit frequency, inability to take regular medications, and utilization of telephone/online medical care), psychological distress, and sociodemographic factors were evaluated at baseline (May 2020) and at the follow-up survey (February 2021). A worsening of chronic diseases was defined as those who answered "yes" to the question, "Has-the-condition-of-the-chronic-disease-worsened?". The factors related to the worsening of chronic diseases at follow-up were examined. Results A total of 514 participants (mean age 61.6±12.9 years) were analyzed. The percentage of participants who reported decreasing medical visit frequency was 34% at the baseline and 16.5% at follow-up, and those who reported a worsening of chronic diseases was 5.1% and 5.1%, respectively. A worsening of chronic diseases at follow-up was significantly associated with a younger age, a decreased frequency of medical visits, unemployment, a history of smoking, and psychological distress. Conclusions A decreased frequency of medical visits was observed among one-third of the participants with chronic disease in the early stage of the pandemic, and it reduced by half at follow-up. In the early stages of an emerging infectious disease pandemic, decreased regular hospital/clinic visits can lead to a worsening of chronic diseases. Those who had psychological distress, unemployment, and a history of smoking were vulnerable to a worsening chronic disease.

Purpose: To evaluate the effectiveness and safety of pre-emptive transcatheter arterial embolization (P-TAE) for aortic side branches (ASBs) to prevent Type 2 endoleaks (EL2) before endovascular aneurysm repair (EVAR) using the Excluder stent-graft system (Excluder)., Materials and Methods: In this prospective, multicenter study, 80 patients (mean age, 79.1 years [SD ± 6.7]; 85.0% were men; mean aneurysmal sac diameter, 48.4 mm [SD ± 7.4]) meeting the eligibility criteria were prospectively enrolled from 9 hospitals. Before EVAR, P-TAE was performed to embolize the patent ASBs originating from the abdominal aortic aneurysm. Contrast-enhanced computed tomography (CT) was performed at 1 month and 6 months after EVAR. The primary endpoint was EL2 incidence at 6 months, and the secondary endpoints were aneurysmal sac diameter changes at 6 and 12 months, P-TAE outcomes, adverse events related to P-TAE, reintervention, and aneurysm-related mortality., Results: All patients successfully underwent P-TAE without serious. Coil embolization was successful in 81.6% of ASBs. EL2 incidence at 6 months was identified in 18 of 70 (25.7%) patients. Aneurysmal sac diameter shrinkage (≥5 mm) was observed in 30.0% of patients at 6 months and in 40.9% at 12 months. Only 1 patient required reintervention for EL2 within 1 year of EVAR; aneurysm-related deaths were not observed., Conclusions: P-TAE for ASBs before EVAR using Excluder is a safe and effective strategy. It aids in achieving early aneurysmal sac shrinkage and reduces EL2 reintervention at 1 year after EVAR., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

Background: The effectiveness of β-blocker in patients with heart failure with preserved ejection fraction (HFpEF) remains to be determined. We aimed to clarify the association between the use of β-blocker and prognosis according to the status of frailty., Methods: We compared prognosis between HFpEF patients with and without β-blockers stratified with the Clinical Frailty Scale (CFS), using data from the PURSUIT-HFpEF registry (UMIN000021831)., Results: Among 1159 patients enrolled in the analysis (median age, 81.4 years; male, 44.7%), 580 patients were CFS ≤ 3, while 579 were CFS ≥ 4. Use of β-blockers was associated with a worse composite endpoint of all-cause death and heart failure readmission in patients with CFS ≥ 4 (adjusted hazard ratio (HR) 1.43, 95% CI 1.10-1.85, p = 0.007), but was not significantly associated with this endpoint in those with CFS ≤ 3 (adjusted HR 0.95, 95% CI 0.71-1.26, p = 0.719) in multivariable Cox proportional hazard models. These results were confirmed in a propensity-matched analysis (HR in those with CFS ≥ 4: 1.42, 95% CI 1.05-1.90, p = 0.020; that in those with CFS ≤ 3: 0.83, 95% CI 0.60-1.14, p = 0.249), and in an analysis in which patients were divided into CFS ≤ 4 and CFS ≥ 5., Conclusions: Use of β-blockers was significantly associated with worse prognosis specifically in patients with HFpEF and high CFS, but not in those with low CFS. Use of β-blockers in HFpEF patients with frailty may need careful attention., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Encephalopathy is the most severe complication of various common infections, including influenza and herpes, and it often results in death or severe neurological disability. The risk factors for viral encephalopathy include non-steroidal anti-inflammatory drug (NSAID) use; however, studies on NSAID-related encephalopathy are limited. In this study, we aimed to investigate the characteristics of NSAID-related encephalopathy. We investigated the incidence of NSAID-related encephalopathy using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases containing reports on spontaneous adverse effects (AEs) published by the Pharmaceuticals and Medical Devices Agency. We used these databases to detect AEs based on reported odds ratios. By separating suspicious drugs, concomitant drugs, and drug interactions involving NSAIDs, we investigated the relationship between encephalopathy pathology and AEs of NSAIDs. Significant encephalopathy signals were detected for loxoprofen and etodolac in the FAERS database and loxoprofen in the JADER database. In the JADER database, significant encephalopathy signals in loxoprofen-treated patients were detected in 70-79-year-old, ≥80-year-old, influenza viral infection, and herpes virus infection groups. Significant encephalopathy signals in patients with herpes virus infection were detected in the ≥80-year-old and loxoprofen-treated groups. Regarding the involvement of loxoprofen in the development of encephalopathy, the JADER database listed loxoprofen as a suspect drug, without indicating any concomitant drug interactions. In conclusion, our findings suggest that loxoprofen and etodolac may be associated with viral encephalopathy. Accordingly, prudence is recommended when using loxoprofen in older individuals with viral infections.

Background: Few studies have been conducted on the usage of telehealth focusing on consultations between patients' families and physicians. This study aimed to identify the usage and limitations of online medical consultations with patients' families compared to the traditional in-person consultations., Methods: We conducted a prospective cohort study from April 1, 2020, to September 30, 2021, at an educational acute-care hospital in Japan. The study included hospitalized patients aged 20 years or older and their family members for whom an online or in-person medical consultation between the family member and physician was conducted during the hospitalization period. The primary endpoints assessed were three topics pertaining to medical consultation: medical conditions and treatment plans, policies for life-threatening events, and post-discharge support. The secondary endpoint was the number of consultations required., Results: Online consultations and traditional in-person consultations were provided to 58 and 53 patients' families, respectively. Of the patients in the online consultation group who underwent multiple consultations, 46 (79%) also underwent in-person consultations. Regarding the topics, all the patients' families in both consultation groups had consultations on medical conditions and treatment plans; regarding the policy for life-threatening events, 47% of patient families in the online consultation group were consulted compared to 53% of those in the in-person group. Regarding post-discharge support, 59% of patient families in the online group were consulted compared to 40% in the in-person group. In the online consultation group of 58 patients' families, 188 consultations were conducted, including 95 online and 93 in-person consultations. Consultations on policy for life-threatening events were significantly more frequent in in-person consultations than in online consultations (p < 0.05). Regarding post-discharge support, online consultations were significantly more frequent than in-person consultations (p < 0.05). The number of family members who attended online consultations was significantly higher than those who attended in-person consultations (p < 0.05)., Conclusions: Online consultation between the physician and patient's family may be an alternative to in-person consultation for explaining medical conditions and treatment plans. However, in-person consultation still plays an important role in sensitive topics, such as policy consultation for life-threatening events., (© 2024. The Author(s).)

Traumatic spinal cord injury (TSCI) causes an insult to the central nervous system, often resulting in devastating temporary or permanent neurological impairment and disability, which places a substantial financial burden on the health-care system. This study aimed to clarify the up-to-date epidemiology and demographics of patients with TSCI treated at the largest SCI center in Japan. Data on all patients admitted to the Spinal Injuries Center with TSCI between May 2005 and December 2021 were prospectively collected using a customized, locally designed SCI database named the Japan Single Center Study for Spinal Cord Injury Database (JSSCI-DB). A total of 1152 patients were identified from the database. The study period was divided into the four- or five-year periods of 2005-2009, 2010-2013, 2014-2017, and 2018-2021 to facilitate the observation of general trends over time. Our results revealed a statistically significant increasing trend in age at injury. Since 2014, the average age of injury has increased to exceed 60 years. The most frequent spinal level affected by the injury was high cervical (C1-C4: 45.8%), followed by low cervical (C5-C8: 26.4%). Incomplete tetraplegia was the most common cause or etiology category of TSCI, accounting for 48.4% of cases. As the number of injuries among the elderly has increased, the injury mechanisms have shifted from high-fall trauma and traffic accidents to falls on level surfaces and downstairs. Incomplete tetraplegia in the elderly due to upper cervical TSCI has also increased over time. The percentage of injured patients with an etiology linked to alcohol use ranged from 13.2% (2005-2008) to 19% (2014-2017). Given that Japan has one of the highest aging populations in the world, epidemiological studies in this country will be very helpful in determining health insurance and medical costs and deciding strategies for the prevention and treatment of TSCI in future aging populations worldwide., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yokota et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Additional surgical resection is recommended after breast-conserving surgery if the surgical margin is pathologically positive. However, in clinical practice, radiation therapy is sometimes used instead for several reasons. Irradiation may be appropriate for some patients, but real-world data is still insufficient to establish it as standard treatment. We retrospectively investigated the status of local control in patients who received irradiation for positive margins., Methods: We investigated 85 patients with positive margins after curative partial mastectomy who were treated with irradiation instead of additional excision during the period 2006-2013. The patients received whole-breast irradiation (43.2-50 Gy) using photon beams and additional tumour-bed boost (8.1-16 Gy) using electron beams. Intrabreast tumour recurrence was defined as secondary cancer within the ipsilateral conserved breast. Surgical margin was defined as positive if tumour cell exposure was pathologically confirmed on the margin., Results: Seven patients (8.2%) developed intrabreast tumour recurrence during a mean observation period of 119 months. As to components of positive margin, 76 cases were positive for an intraductal component, of which seven (9.2%) developed intrabreast tumour recurrence. Meanwhile, all nine cases positive for an invasive component were free from intrabreast tumour recurrence. Two of the intrabreast tumour recurrence cases seemed to develop new lesions rather than recurrence, considering tumour location. The cumulative incidence of intrabreast tumour recurrence over 10 years was 6.1%. Limited to true recurrence, intrabreast tumour recurrence incidence was 4.9%., Conclusion: Our real-world data supports irradiation as an alternative to additional surgical intervention for positive margins after breast-conserving surgery and offers a basis for further research., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: The aim of this study was to estimate the number of patients in Japan who had visited an ophthalmologist for macular dystrophy of various types, including Best vitelliform macular dystrophy (BVMD), Stargardt disease, occult macular dystrophy (OMD), cone (-rod) dystrophy, X-linked retinoschisis (XLRS), and central areolar choroid dystrophy (CACD)., Study Design: Nationwide epidemiologic survey METHODS: Questionnaires were distributed to 965 major facilities, including all the university hospitals in Japan. The aim of the questionnaire was to determine the number of patients with each type of macular dystrophy who had visited an outpatient clinic during the past 5 years (January 2015 to December 2019)., Results: Over 70% of the patients were diagnosed and followed up at university hospitals. The estimated annual number of newly diagnosed cases was as follows: 55.3 for BVMD, 36.7 for Stargardt disease, 35.8 for OMD, 160.6 for cone (-rod) dystrophy, 31.0 for XLRS, 29.8 for CACD, and 174.1 for other types of macular dystrophy. The total number of patients with macular dystrophy diagnosed and followed at major institutions was estimated to be 6651., Conclusion: This was the first nationwide survey of macular dystrophy in Japan and provided an approximate number of affected patients. The diagnosis of macular dystrophy is primarily carried out at facilities with affiliated specialists, such as university hospitals. By examining the incidence of multiple diseases simultaneously, we were able to compare the incidence of each type of macular dystrophy., (© 2024. Japanese Ophthalmological Society.)

Purpose: In Japan, the vehicle used in pre-hospital trauma care systems with physician-staffed ground emergency medical services (GEMS) is referred to as a "doctor car". Doctor cars are highly mobile physician-staffed GEMS that can provide complex pre-hospital trauma management using various treatment strategies. The number of doctor car operations for patients with severe trauma has increased. Considering facility factors, the association between doctor cars and patient outcomes remains unclear. Therefore, this study aimed to examine the relationship between doctor cars for patients with severe trauma and survival outcomes in Japan., Methods: A nationwide retrospective cohort study was conducted to compare the impact of the doctor car group with the non-physician-staffed GEMS group on in-hospital survival in adult patients with severe trauma. The data were analyzed using multivariable logistic regression models with generalized estimating equations., Results: This study included 372,365 patients registered in the Japan Trauma Data Bank between April 2009 and March 2019. Of the 49,144 eligible patients, 2361 and 46,783 were classified into the doctor car and non-physician staffed GEMS groups, respectively. The adjusted odds ratio (OR) for survival was significantly higher in the doctor car group than in the non-physician staffed GEMS group (adjusted OR = 1.228 [95% confidence interval 1.065-1.415])., Conclusion: Using nationwide data, this novel study suggests that doctor cars improve the in-hospital survival rate of patients with severe trauma in Japan. Therefore, doctor cars could be an option for trauma strategies., (© 2023. The Author(s).)

Background: Glomerular hyperfiltration has been reported to be associated with adverse renal outcomes in the general population. It is not known whether drinking pattern is associated with the risk of glomerular hyperfiltration in healthy individuals., Methods: We prospectively followed middle-aged 8,640 Japanese men with normal renal function, no proteinuria, no diabetes, and no use of antihypertensive medications at entry. Data on alcohol consumption were gathered by questionnaire. Glomerular hyperfiltration was defined as estimated glomerular filtration rate (eGFR) ≥117 mL/min/1.73 m 2 , which was the upper 2.5th percentile value of eGFR in the entire cohort., Results: During 46,186 person-years of follow-up, 330 men developed glomerular hyperfiltration. In a multivariate model, for men who consumed alcohol on 1-3 days per week, alcohol consumption of ≥69.1 g ethanol/drinking day was significantly associated with the risk of glomerular hyperfiltration (hazard ratio [HR] 2.37; 95% confidence interval [CI], 1.18-4.74) compared with non-drinkers. For those who consumed alcohol on 4-7 days per week, higher alcohol consumption per drinking day was associated with a higher risk of glomerular hyperfiltration: the HRs for alcohol consumption of 46.1-69.0, and ≥69.1 g ethanol/drinking day were 1.55 (95% CI, 1.01-2.38), and 1.78 (95% CI, 1.02-3.12), respectively., Conclusion: For high drinking frequency per week, more alcohol intake per drinking day was associated with an increased risk of glomerular hyperfiltration, while for low drinking frequency per week, only very high alcohol intake per drinking day was associated with an increased risk of glomerular hyperfiltration in middle-aged Japanese men.