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Abstract Aims A fourth heart sound (S4) was reported to be almost never present in patients with amyloid light‐chain cardiomyopathy. There have been no reports on S4 in patients with wild‐type transthyretin amyloid cardiomyopathy (ATTRwt‐CM). This study aimed to clarify the clinical implications of S4 in patients with ATTRwt‐CM. Methods and results Seventy‐six patients with ATTRwt‐CM (mean age: 80.4 ± 5.4 years, 68 males) who had undergone phonocardiography (PCG) were retrospectively assessed. We measured S4 amplitude on digitally recorded PCG. S4 was considered to be present when its amplitude was 1.0 mm or greater on the PCG. Distinct S4 was defined as S4 with an amplitude of 2.0 mm or greater, which is usually recognizable by auscultation. According to the rhythm and presence or absence of S4, the patients were divided into three groups, namely, sinus rhythm (SR) with S4, SR without S4, and non‐SR. Non‐SR consisted of atrial fibrillation, atrial flutter, and atrial tachycardia. Thirty‐six patients were in SR and the remaining 40 patients were in non‐SR. In the 36 patients in SR, S4 was shown by PCG to be present in 17 patients (47%), and distinct S4 was recognized in 7 patients (19%) by auscultation. In patients who were in SR, those with S4 had higher systolic blood pressure (124 ± 15 vs. 99 ± 8 mmHg, P

ABSTRACT Aims/Introduction This study aimed to evaluate the problems in screening for gestational diabetes mellitus (GDM) by casual blood glucose (CBG) measurements at 24–28 gestational weeks. Materials and Methods Overall, 763 pregnant women who underwent the 50‐g glucose challenge test (GCT) at 24–28 gestational weeks were enrolled. The preload blood glucose (0‐h BG) level of 50‐g GCT was considered as CBG. Results A total of 240 women with BG levels at 1‐h after loading (1‐h BG) on 50‐g GCT ≥140 mg/dL underwent the 75‐g oral glucose tolerance test, and 98 (40.8%) were diagnosed with GDM. Of the 99 women with GDM, 71 (71.7%) had 0‐h BG on 50‐g GCT

ABSTRACT Aims/Introduction Insulin resistance syndrome and lipoatrophic diabetes are rare conditions characterized by the development of treatment‐refractory diabetes with severe insulin resistance. We recently conducted a 24 week, multicenter, single‐arm trial (EMPIRE‐01) that demonstrated a certain level of effectiveness and safety of empagliflozin for these conditions. To evaluate treatment safety over a longer period, we have now performed an additional 28 week trial (EMPIRE‐02) that followed on from EMPIRE‐01. Materials and Methods The primary and secondary outcomes were safety and efficacy evaluations, respectively. All eight subjects of the EMPIRE‐01 trial participated in EMPIRE‐02. Results Twenty adverse events (AEs) were recorded among five individuals during the combined 52 week treatment period of both trials. Whereas one case of chronic hepatitis B was moderate in severity, all other AEs were mild. There were thus no serious AEs or events necessitating discontinuation or suspension of treatment or a reduction in drug dose. Whereas ketoacidosis or marked increases in serum ketone body levels were not observed, the mean body mass of the subjects was decreased slightly after completion of EMPIRE‐02. The improvement in mean values of glycemic parameters observed in EMPIRE‐01 was not sustained in EMPIRE‐02, mostly because of one individual whose parameters deteriorated markedly, likely as a result of nonadherence to diet therapy. The improvement in glycemic parameters was sustained during EMPIRE‐02 after exclusion of this subject from analysis. Conclusions Empagliflozin demonstrated a certain level of safety and efficacy for the treatment of insulin resistance syndrome and lipoatrophic diabetes over 52 weeks, confirming its potential as a therapeutic option.

Background Using machine learning for the phenotyping of patients with heart failure with preserved ejection fraction (HFpEF) has emerged as a novel approach to understanding the pathophysiology and stratifying the patients. Our objective is to perform phenotyping of patients with HFpEF in stable phase and to investigate the phenotypic trajectory from acute worsening phase to stable phase. Methods The present study is a post hoc analysis of the PURSUIT‐HFpEF (Prospective Multicenter Observational Study of Patients with Heart Failure with Preserved Ejection Fraction) study. We applied the latent class analysis to the discharge data of patients hospitalized for acute decompensated heart failure. Results We finally included patient data of 1100 cases and 63 features in the latent class analysis. All patients were subclassified into 5 phenogroups as follows: Phenotype 1, characterized by better renal function and lower NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) level [N=325 (29.5%)]; Phenotype 2, higher blood pressure, sinus rhythm, and poor renal function. [N=242 (22.0%)]; Phenotype 3, higher prevalence of atrial fibrillation, higher tricuspid pressure gradient, and lower tricuspid annular plane systolic excursion [N=214 (19.5%)]; Phenotype 4, higher C‐reactive protein level and higher tricuspid pressure gradient [N=245 (22.3%)]; and Phenotype 5, poor nutritional status, poor renal function, and higher NT‐proBNP level [N=74 (6.7%)]. A particular phenotype observed at the time of discharge was correlated with a distinct phenotype of acute worsening. Conclusions We identified 5 distinct stable phase phenotypes of the patients with HFpEF from the data at discharge. A specific phenotype at discharge was associated with a particular phenotype of acute worsening. This grouping can be a basis for future precision medicine of patients with HFpEF. Registration URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000021831.

ABSTRACT The genus Camellia is widely distributed, primarily in East Asia. Camellia japonica is located at the northern limit of this genus distribution, and understanding changes in its distribution is crucial for understanding the evolution of plants in this region, as well as their relationship with geological history and climate change. Moreover, the classification of sect. Camellia in Japan has not been clarified. Therefore, this study aims to understand the evolutionary history of the Japanese sect. Camellia. The genetic population structure was analysed using SNP data and MIG‐seq. The relationship between the Japanese sect. Camellia, including the related species in China, was further inferred from the phylogeny generated by RA x ML, SplitsTree and PCA. Population genetic structure was inferred using a Bayesian clustering method (ADMIXTURE). We subsequently employed approximate Bayesian computation, which was further supported by the coalescent simulations (DIYABC, fastsimcoal and Bayesian Skyline Plots) to explore the changes in population, determining which events appropriately explain the phylogeographical signature. Ecological niche modelling was combined with genetic analyses to compare current and past distributions. The analyses consistently showed that C. japonica and C. rusticana are distinct, having diverged from each other during the Middle to Late Miocene period. Furthermore, C. japonica differentiated into four major populations (North, South, Ryukyu‐Taiwan and Continent). The Japanese sect. Camellia underwent speciation during archipelago formation, reflecting its ancient evolutionary history compared with other native Japanese plants. C. rusticana did not diverge from C. japonica in snow‐rich environments during the Quaternary period. Our results suggest that both species have been independent since ancient times and that ancestral populations of C. japonica have persisted in northern regions. Furthermore, the C. japonica population on the continent is hypothesised to have experienced a reverse‐colonisation event from southern Japan during the late Pleistocene glaciation.

Abstract Anthropogenic activities have reduced ecotones between the ocean and land, which is likely to threaten the population of brackish‐water brachyuran crabs. To assess the current status of these crabs, we examine the population genetic structures of three semi‐terrestrial brachyuran crabs widely distributed along the coast of the Japan and to clarify factors determining their genetic structures. We collected 184 Orisarma dehaani, 252 Chiromantes haematocheir, and 151 Helice tridens crabs from 36 localities of the Japanese archipelago. Genome‐wide SNP data from these crabs were analyzed using MIG‐seq. Bayesian clustering of STRUCTURE and DAPC analysis were used to identify genetically disturbed populations and to visualize genetic differentiation between local populations. Genetic population structure showed clear differentiation between populations on the Pacific coast of the Tohoku region and on other Japanese coasts in O. dehaani, but not in C. haematocheir or H. tridens. The inbreeding coefficient of O. dehaani was significantly higher on the Pacific coast of the Tohoku region compared to other Japanese coasts. C. haematocheir and H. tridens had homogeneous genetic structures along the Japanese coast, but showed genetic differentiation of a local population at their range limits. Thus, O. dehaani showed little gene flow and clear genetic differentiation between populations in the Tohoku Pacific region and those on other Japanese coasts due to ocean currents. Although such a regional differentiation was not found in C. haematocheir and H. tridens, one population of C. haematocheir was genetically isolated at the edge of its distribution range and likely vulnerable to environmental changes.

Abstract As plant distribution and performance are determined by both environmental and genetic factors, clarifying the contribution of these two factors is a key for understanding plant adaptation and predicting their distribution under ongoing global warming. Betula ermanii is an ideal species for such research because of its wide distribution across diverse environments. Stomatal density and size are crucial traits that plants undergo changes in to adapt to different environments as these traits directly influence plant photosynthesis and transpiration. In this study, we conducted a multi‐location common garden experiment using B. ermanii to (1) clarify the contribution of both environmental and genetic factors to the variation in stomatal density and size of B. ermanii, (2) demonstrate the differences in the plasticity of stomatal density and size among B. ermanii populations, and (3) understand how stomatal density and size of B. ermanii would respond to increased temperature and changing precipitation patterns. Genetic factors played a more significant role in stomatal size than environmental factors, suggesting that B. ermanii struggles to adjust its stomatal size in response to a changing environment. Our results also revealed a positive correlation between stomatal size plasticity and original habitat suitability, indicating that in B. ermanii populations in harsh environments exhibit lower adaptability to environmental shifts. Although stomatal density and size of B. ermanii showed the significant responses to increased temperature and shifting precipitation patterns, the response ranges of stomatal density and size to the environmental factors varied among populations. Our findings highlighted the interplay between genetic and environmental factors in determining the intraspecific variation in stomatal density and size in B. ermanii. This indicated that certain populations of B. ermanii exhibit limited stomatal plasticity and adaptability, which could directly affect photosynthesis and transpiration, suggesting potential population‐specific fitness implications for B. ermanii under future climate change.

Abstract Background With the aging of heart failure (HF) patients, collaboration between medical and nursing care facilities is essential for HF care. The aims of this study were: (1) to identify the factors that affect willingness of nursing care staffs to cooperate with HF care; (2) to test whether the internet video education is useful in improving their willingness to collaborate. Methods A web‐based questionnaire was e‐mailed to 417 registered medical corporations that operated nursing care facilities in the prefecture where the authors work. Medical and care staff working at each facility were asked their willingness to cooperate with HF care and their problems about collaboration. Machine learning analysis was used to assess the factors associated with unwillingness to cooperate. After watching a 6‐min YouTube video explaining HF and community collaboration, we reaffirmed their willingness to cooperate. Results We received responses from 76 medical and care staff members. Before watching the video, 32.9% of participants stated that they were unwilling to cooperate with HF care. Machine learning analysis showed that job types, perceived problems of collaboration, and low opportunities to learn about HF were associated with unwillingness to cooperation. After watching the video, we observed an increase from 67.1% to 80.3% (p

Abstract Aims/Introduction To evaluate the efficacy of sensor‐augmented pump (SAP) for improving obstetric and neonatal outcomes among pregnant women with type 1 diabetes mellitus by comparing it with continuous subcutaneous insulin infusion plus self‐monitoring of blood glucose (continuous subcutaneous insulin infusion [CSII]/SMBG). Materials and Methods This retrospective cohort study included 40 cases of pregnancy complicated by type 1 diabetes mellitus treated with SAP (SAP group), and 29 cases of pregnancy complicated by type 1 diabetes mellitus treated with CSII/SMBG (CSII/SMBG group). The obstetric and neonatal outcomes were compared between the two groups. Results The median of the glycoalbumin levels in the first (18.8% vs 20.9%; P

ABSTRACT Aims/Introduction Polypharmacy in diabetes patients is related to worse clinical outcomes. The aim of this study was to evaluate the usefulness of our countermeasure for polypharmacy, which combines a pharmacist check followed by a multidisciplinary team review in diabetic patients with polypharmacy. Methods A single‐center, retrospective observational study was conducted at Gifu University Hospital. Study participants included diabetic patients taking six or more drugs on admission to the diabetes ward between July 2021 and June 2022. Drugs which were discontinued by the present countermeasure were examined, and the number of drugs being taken by each patient was compared between admission and discharge. Results 102 of 308 patients were taking six or more drugs on admission. The drugs being taken by these patients were evaluated by pharmacists using a checklist for polypharmacy. Eighty‐four drugs which were evaluated as inappropriate or potentially inappropriate medications by pharmacists were discontinued following the multidisciplinary team review. The median and mean number of drugs taken by the 102 patients significantly decreased from 9.0 (IQR: 8–12) and 9.26 ± 2.64 on admission to 9.0 (IQR: 6–10) and 8.42 ± 2.95 on discharge (P = 0.0002). We followed up with these patients after discontinuation of the drugs and confirmed that their clinical status had not deteriorated. Conclusion The present countermeasure for polypharmacy, which combines a pharmacist check based on a checklist for evaluating polypharmacy followed by a multidisciplinary team review, was useful for reducing the number of inappropriate or potentially inappropriate medications taken by diabetes patients with polypharmacy.

ABSTRACT Aims/Introduction To investigate whether the COVID‐19 pandemic affected behavioral changes and glycemic control in patients with diabetes and to conduct a survey of telemedicine during the pandemic. Materials and Methods In this retrospective study, a total of 2,348 patients were included from 15 medical facilities. Patients were surveyed about their lifestyle changes and attitudes toward telemedicine. Hemoglobin A1c (HbA1c) levels were compared among before (from June 1 to August 31, 2019) and in the first (from June 1 to August 31, 2020) and in the second (from June 1 to August 31, 2021) year of the pandemic. A survey of physician attitudes toward telemedicine was also conducted. Results The HbA1c levels were comparable between 2019 (7.27 ± 0.97%), 2020 (7.28 ± 0.92%), and 2021 (7.25 ± 0.94%) without statistical difference between each of those 3 years. Prescriptions for diabetes medications increased during the period. The frequency of eating out was drastically reduced (51.7% in 2019; 30.1% in 2020), and physical activity decreased during the pandemic (48.1% in 2019; 41.4% in 2020; 43.3% in 2021). Both patients and physicians cited increased convenience and reduced risk of infection as their expectations for telemedicine, while the lack of physician–patient interaction and the impossibility of consultation and examination were cited as sources of concern. Conclusions Our data suggest that glycemic control did not deteriorate during the COVID‐19 pandemic with appropriate intensification of diabetes treatment in patients with diabetes who continued to attend specialized diabetes care facilities, and that patients and physicians shared the same expectations and concerns about telemedicine.

Introduction We present a case of mucinous adenocarcinoma of the prostate with testicular and lung metastases following robot‐assisted radical prostatectomy, androgen deprivation therapy, and radiotherapy. Case presentation A 73‐year‐old man with a prostate‐specific antigen level of 4.3 ng/mL was diagnosed with prostate cancer. Following the robot‐assisted radical prostatectomy, the pathological diagnosis was mucinous adenocarcinoma of the prostate (pT3bpN0, Gleason score of 4 + 4). Salvage hormonal therapy and irradiation were performed after the prostatectomy. Enlargement of the left testis was noted, and 28 months after prostatectomy, computed tomography detected a left testicular tumor and nodular lesions in the bilateral lungs. The histopathological diagnosis of left high orchiectomy was metastasis of a mucinous adenocarcinoma of the prostate. Chemotherapy with docetaxel followed by cabazitaxel was initiated. Conclusion Mucinous prostate adenocarcinoma with distal metastases following prostatectomy has been managed for longer than 3 years with multiple treatments.

Abstract Background Since it was first reported in December 2019, coronavirus disease 2019 (COVID‐19) spread rapidly across the globe resulting in a pandemic. As of August 2022, seven outbreak peaks have been confirmed in Tokyo, and the numbers of new cases in the fifth and later outbreak periods have been far greater than in the preceding periods. This retrospective study examined the impact of the COVID‐19 pandemic on perioperative chemotherapy for breast cancer. Methods Patients with breast cancer who received perioperative chemotherapy at the National Cancer Center Hospital East were divided into 2 groups: 120 and 384 patients who started chemotherapy before and during the pandemic, respectively. The incidence of critical events that had potential detrimental effects on the prognosis, such as start of adjuvant chemotherapy ≥91 days after surgery and relative dose intensity of chemotherapy

Abstract Background and Aim Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer, partly because its early detection is difficult. This study aimed to identify computed tomography (CT) findings associated with PDAC prior to diagnosis. Methods Past CT images were retrospectively collected from the PDAC group (n = 54) and the control group (n = 90). The following imaging findings were compared: pancreatic mass, main pancreatic duct (MPD) dilatation with or without cutoff, cyst, chronic pancreatitis with calcification, partial parenchymal atrophy (PPA), and diffuse parenchymal atrophy (DPA). In the PDAC group, CT findings were examined during the pre‐diagnostic period and 6–36 months and 36–60 months before diagnosis. Multivariate analyses were performed using logistic regression. Results MPD dilatation with cutoff (P

Abstract Background Early pregnancy events, including embryo implantation, are critical for maintaining a healthy pregnancy and facilitating childbirth. Despite numerous signaling pathways implicated in establishing early pregnancy, a comprehensive understanding of implantation remains elusive. Methods This paper provides a comprehensive review of the current research on lipids in the context of early pregnancy, with a particular focus on feto‐maternal communications. Main Findings Embryo implantation entails direct interaction between uterine tissues and embryos. Introducing embryos triggers significant changes in uterine epithelial morphology and stromal differentiation, facilitating embryo implantation through communication with uterine tissue. Studies employing genetic models and chemical compounds targeting enzymes and receptors have elucidated the crucial roles of lipid mediators—prostaglandins, lysophosphatidic acid, sphingosine‐1‐phosphate, and cannabinoids—in early pregnancy events. Conclusion Given the high conservation of lipid synthases and receptors across species, lipid mediators likely play pivotal roles in rodents and humans. Further investigations into lipids hold promise for developing novel diagnostic and therapeutic approaches for infertility in humans.

ABSTRACT Aims/Introduction The discrepancy between HbA1c and glucose exposure may have significant clinical implications; however, the association between the hemoglobin glycation index (HGI) and clinical parameters in type 1 diabetes remains controversial. This study aimed to find the factors associated with HGI (laboratory HbA1c − predicted HbA1c derived from the continuous glucose monitoring [CGM]). Materials and Methods We conducted a cross‐sectional study of adults with type 1 diabetes (n = 211, age 50.9 ± 15.2 years old, female sex = 59.2%, duration of CGM use = 2.1 ± 1.0 years). All subjects wore the CGM for 90 days before HbA1c measurement. Data derived from the FreeStyle Libre sensor were used to calculate the glucose management indicator (GMI) and glycemic variability (GV) parameters. HGI was defined as the difference between the GMI and the laboratory HbA1c levels. The participants were divided into three groups according to the HGI tertile (low, moderate, and high). Multivariate regression analyses were performed. Results The female sex ratio, HbA1c, and % coefficient of variation (%CV) significantly increased over the HGI tertile, while eGFR and Hb decreased over the HGI tertile. In multivariate analysis, the factors associated with HGI were %CV and eGFR, after adjusting for HbA1c level and sex (R2 = 0.44). Conclusions This study demonstrated that HGI is associated with female sex, eGFR, and some glycemic variability indices, independently of HbA1c. Minimizing glycemic fluctuations might reduce HGI. This information provides diabetic health professionals and patients with personalized diabetes management for adults with type 1 diabetes.

Abstract Background Interatrial conduction time (IACT) prolongs in fibrotic left atrium. We tested the hypothesis that IACT is related to left atrial low voltage area (LVA) and predicts the recurrence after single atrial fibrillation (AF) ablation. Methods One hundred sixty‐four consecutive AF patients (79 non‐paroxysmal) who underwent initial ablation in our institute were analyzed. IACT and LVA were defined as interval from the onset of P‐wave to the basal left atrial appendage (P‐LAA) activation, and area with bipolar electrogram < 0.5 mV covering over 5% of the total left atrial surface area during sinus rhythm, respectively. Pulmonary vein antrum isolation, non‐PV foci ablation, and atrial tachycardia (AT) ablation were performed without substrate modification. Results LVA was frequently identified in patients with prolonged P‐LAA ≥ 84 ms (n = 28) compared with patients with P‐LAA

Abstract We developed a low‐intensity 10‐min resistance exercise program for nonalcoholic fatty liver disease (NAFLD). We report a case of NAFLD with elevated hepatic fibrosis indices, which were improved by a 60‐week daily exercise program. A 71‐year‐old female patient with NAFLD whose hepatic fibrosis stage corresponded to F2 was referred to our hospital. She performed the exercise once a day with no changes in other lifestyle habits and medications. The homeostasis model assessment‐insulin resistance value and NAFLD‐liver fat score, the Hepamet fibrosis score, and the enhanced liver fibrosis score decreased. The FIB‐4 index and serum levels of Mac‐2 binding protein glycosylation isomer decreased to the reference values. We investigated the changes in chemokines/cytokines. The serum granulocyte‐colony stimulating factor level was increased, and serum interferon‐gamma‐induced protein‐10 and platelet‐derived growth factor‐BB levels were decreased. Our program may be beneficial for improving hepatic fibrosis in patients with NAFLD.

Abstract Background and Aim The number of patients with ulcerative colitis (UC) has been increasing in Japan. To elucidate the risk factors for developing UC in Japan, a hospital‐based case–control study was conducted. This study examined the association between smoking/drinking habits and UC onset in detail. Methods Cases comprised 132 Japanese patients who had been newly diagnosed with UC between 2008 and 2014 at 38 collaborating hospitals in Japan, and controls comprised 167 patients without UC. Detailed data on smoking and drinking habits were collected using a self‐administered questionnaire. Results Ex‐smokers showed an increasing odds ratio (OR) for UC development compared with never smokers (OR 2.42, 95% confidence interval 1.24–4.72). The ORs of ex‐smokers were particularly high among subjects aged less than 40 years, subjects who had smoked more than 10 pack‐years, and subjects who were within 13 years of quitting smoking. Regarding drinking habits, ex‐drinkers also showed a more than twofold higher OR for UC compared to never drinkers. Ex‐drinkers 40 years or older, ex‐drinkers who had consumed more than 364 drink‐years, and subjects who were less than 6 years after quitting drinking showed increased ORs for UC. Conclusion These findings suggest the need for careful attention for UC onset among heavy smokers who quit smoking before 40 years of age and heavy drinkers who quit drinking at ≥40 years of age.

Abstract The Kakioka Magnetic Observatory (KMO) of the Japan Meteorological Agency (JMA) made geoelectric field observations at Kakioka, Memambetsu and Kanoya from 1932, 1949 and 1948, respectively, until February 2021, when observations at all three sites were terminated. The digital numerical data are available on the KMO website, although not all observation periods are covered. In this article, we introduce the available datasets and summarize the metadata regarding the observations, such as the electrodes, recording system, maintenance methods and data processing.

Abstract The Kakioka Magnetic Observatory (KMO) of the Japan Meteorological Agency (JMA) made atmospheric electric field observations at Kakioka and Memambetsu beginning in 1929 and 1949, respectively, and ending in February 2021 and December 2010, respectively. The digital numerical data are available on the KMO website, although not all observation periods are covered. In this article, we introduce the available datasets and summarize the metadata regarding the observations, such as measurement instruments, maintenance methods and data processing.

Abstract Background Under‐sensing (US) in implantable loop recorders (ILRs) interferes with the accurate diagnosis of arrhythmia, but there is little information available on the details of US of ILRs. The aim of this study was to clarify the frequency of US in patients with ILRs and to investigate the predictors of US in ILRs prior to implantation. Methods and Results We studied 46 consecutive patients implanted ILR. During the mean follow‐up period of 499 ± 363 days, 15 events of US were observed in five patients. There were no significant differences in patient characteristics between patients with and without US. In standard 12‐lead electrocardiogram (ECG), QRS complex amplitude in anterolateral chest leads (V2 to V5) were significantly lower in patients with than without US (V2: 0.88 [0.66, 1.22] mV vs. 1.67 [1.23, 2.29] mV, p = .010 V3: 1.25 [1.00, 1.26] mV vs. 1.90 [1.41, 2.29] mV, p = .013; V4: 1.14 [0.96, 1.38] mV vs. 1.93 [1.65, 2.64] mV, p = .023; V5: 0.57 [0.50, 0.75] mV vs. 1.60 [1.20, 1.98] mV, p = .011, respectively). ROC curve analysis showed that cut‐off values of 1.30 mV of QRS complex amplitude in V2, 1.26 mV of that in V3, and 0.75 mV of that in V5 had moderate accuracy for predicting US (V2: sensitivity 68%, specificity 100%, area under the curve [AUC] 0.86; V3: sensitivity 85%, specificity 80%, AUC 0.85; V5: sensitivity 98%, specificity 80%, AUC 0.85, respectively). Conclusions US was observed in 10.9% patients with an ILR. QRS complex amplitude in anterolateral chest leads (V2 to V5) on ECG might be useful for predicting US in patients with ILRs.

Abstract Aims/Introduction The bone mineral density in patients with type 1 diabetes mellitus is reduced due to impaired insulin secretion. However, it is unclear whether the rate of bone mineral density reduction is affected by the type 1 diabetes mellitus subtype. This study aimed to clarify the difference in bone mineral density across type 1 diabetes mellitus subtypes: slowly progressive (SP), acute‐onset (AO), and fulminant (F). Methods This was a retrospective, single‐center, cross‐sectional study conducted on 98 adult type 1 diabetes mellitus patients. The main outcome included the bone mineral density Z‐score (BMD‐Z) measured at the lumbar spine and femoral neck. Results The lumbar spine BMD‐Z was lower in the acute‐onset than in the slowly progressive subtype (P = 0.03). No differences were observed when compared with the fulminant subtype. The femoral neck BMD‐Z tended to be higher in the slowly progressive than in the acute‐onset and fulminant subtypes. Multiple regression analyses showed that the lumbar spine BMD‐Z was associated with subtypes (AO vs SP) (P = 0.01), but not subtypes (F vs SP), adjusted for sex, duration, retinopathy, and C‐peptide immunoreactivity (CPR). When the patients were divided into disease duration tertiles, in the first and second tertiles, the CPR levels were lower in the acute‐onset or fulminant than in the slowly progressive subtype. In contrast, the lumbar spine and femoral neck BMD‐Z differed between the acute‐onset and slowly progressive only in the second tertiles (both P

Abstract Background Decreased swallowing function is an important risk factor for the development of aspiration pneumonia. A previous study reported that a long duration of fasting decreased swallowing function and increased mortality. The purpose of this study is to clarify the relationship between weekend hospitalization and fasting duration in older patients with aspiration pneumonia. Methods In this retrospective cohort study using hospital claims data and electronic medical record data between April 1, 2018, and March 31, 2020, 238 patients hospitalized for aspiration pneumonia were enrolled. Patients admitted from Monday to Friday were defined as the weekday admission group, and patients admitted on Saturday, Sunday, and holidays were defined as the weekend admission group. The primary endpoint was the duration of fasting. Multiple regression analysis was performed with age, gender, place of living, Functional Oral Intake Scale before admission, severity of pneumonia, and weekend admission as the independent variables. Results There were 41 patients in the weekend admission group and 103 patients in the weekday admission group. The baseline characteristics of the two groups were similar. There was a median difference in the fasting duration of 23.3 h; the fasting duration in the weekend admission group was significantly longer than the weekday admission group by 20.03 h (95% confidence interval: 2.81–37.25) in the multiple regression analysis. Conclusions Weekend hospitalization was significantly associated with a longer fasting duration in patients hospitalized for aspiration pneumonia. There is a need to establish a system to enable early meal initiation for patients admitted on weekends.

Abstract Aims We aim to clarify the prognosis on patients with hypertrophic cardiomyopathy (HCM) for a follow‐up period of more than 10 years. Methods and results We retrospectively analysed 102 consecutive patients with HCM diagnosed by 31 December 2000. Complete and detailed clinical records were obtained for 93 (91%) of the 102 patients. Sixty‐three (68%) of the 93 patients were men, and the mean age of the patients at the initial evaluation was 51.5 ± 13.0 years. During the mean follow‐up period of 19.6 ± 8.1 years (median 20.1 years), HCM‐related deaths occurred in 20 patients (21% [1.1%/year]). HCM‐related adverse events (including HCM‐related deaths and nonfatal HCM‐related events: hospitalization for heart failure, embolic stroke admission, and sustained ventricular tachycardia with haemodynamic instability or appropriate implantable cardioverter‐defibrillator discharge) occurred in 45 patients (48%). The first HCM‐related adverse events occurred in approximately 20% of the patients in every decade, the first decade to the third decade, from the initial evaluation. Forty‐seven patients (51%) had documentation of atrial fibrillation at the last follow‐up. There were seven patients in the end‐stage HCM group at the initial evaluation, and 22 patients (24%) had progression to end‐stage HCM during the follow‐up period. Conclusions In our cohort of patients, HCM‐related mortality was relatively favourable. However, approximately half of the patients suffered from HCM‐related adverse events during the follow‐up period of 20 years. It is important for HCM patients to be carefully followed up over the long‐term because HCM is a lifelong disease.

Abstract Aims Application of the latent class analysis to acute heart failure with preserved ejection fraction (HFpEF) showed that the heterogeneous acute HFpEF patients can be classified into four distinct phenotypes with different clinical outcomes. This model‐based clustering required a total of 32 variables to be included. However, this large number of variables will impair the clinical application of this classification algorithm. This study aimed to identify the minimal number of variables for the development of optimal subphenotyping model. Methods and results This study is a post hoc analysis of the PURSUIT‐HFpEF study (N = 1095), a prospective, multi‐referral centre, observational study of acute HFpEF [UMIN000021831]. We previously applied the latent class analysis to the PURSUIT‐HFpEF dataset and established the full 32‐variable model for subphenotyping. In this study, we used the Cohen's kappa statistic to investigate the minimal number of discriminatory variables needed to accurately classify the phenogroups in comparison with the full 32‐variable model. Cohen's kappa statistic of the top‐X number of discriminatory variables compared with the full 32‐variable derivation model showed that the models with ≥16 discriminatory variables showed kappa value of >0.8, suggesting that the minimal number of discriminatory variables for the optimal phenotyping model was 16. The 16‐variable model consists of C‐reactive protein, creatinine, gamma‐glutamyl transferase, brain natriuretic peptide, white blood cells, systolic blood pressure, fasting blood sugar, triglyceride, clinical scenario classification, infection‐triggered acute decompensated HF, estimated glomerular filtration rate, platelets, neutrophils, GWTG‐HF (Get With The Guidelines‐Heart Failure) risk score, chronic kidney disease, and CONUT (Controlling Nutritional Status) score. Characteristics and clinical outcomes of the four phenotypes subclassified by the minimal 16‐variable model were consistent with those by the full 32‐variable model. The four phenotypes were labelled based on their characteristics as ‘rhythm trouble’, ‘ventricular‐arterial uncoupling’, ‘low output and systemic congestion’, and ‘systemic failure’, respectively. Conclusions The phenotyping model with top 16 variables showed almost perfect agreement with the full 32‐variable model. The minimal model may enhance the future clinical application of this clustering algorithm.

Abstract Background Cachexia is a life‐threatening condition observed in several pathologies, such as cancer or chronic diseases. Interleukin 10 (Il10) gene transfer is known to improve cachexia by downregulating Il6. Here, we used an IL10‐knockout mouse model to simulate cachexia and investigate the effects of eggshell membrane (ESM), a resistant protein, on general pre‐cachexia symptoms, which is particularly important for the development of cachexia therapeutics. Methods Five‐week‐old male C57BL6/J mice were fed an AIN‐93G powdered diet (WT), and 5‐week‐old male B6.129P2‐Il10 /J (IL10−/−) mice were fed either the AIN‐93G diet (KO) or an 8% ESM‐containing diet (KOE) for 28 weeks. The tissue weight and levels of anaemia‐, blood glucose‐, lipid metabolism‐, and muscular and colonic inflammation‐related biochemical markers were measured. Transcriptomic analysis on liver and colon mucus and proteomic analysis on skeletal muscle were performed. Ingenuity Pathway Analysis was used to identify molecular pathways and networks. Caecal short‐chain fatty acids (SCFAs) were identified using HPLC, and caecal bacteria DNA were subjected to metagenomic analysis. Flow cytometry analysis was performed to measure the CD4+ IL17+ T cells in mesenteric lymph nodes. Results The body weight, weight of gastrocnemius muscle and fat tissues, colon weight/length ratio, plasma HDL and NEFA, muscular PECAM‐1 levels (P 1.5‐fold). Transcriptomic analysis revealed that ESM supplementation suppressed the LPS/IL1‐mediated inhibition of RXR function pathway in the liver and downregulated the colonic mucosal expression of chemokines and Th cell differentiation‐related markers (P

Abstract Aims The effectiveness of angiotensin‐converting enzyme inhibitors (ACE‐I) and angiotensin II receptor blockers (ARB) has not been demonstrated in patients with heart failure with preserved ejection fraction (HFpEF). We recently reported significant interaction between the use of ACE‐I and/or ARB (ACE‐I/ARB) and frailty on prognosis in patients with HFpEF. In the present study, we examined the association between ACE‐I/ARB and prognosis in patients with HFpEF stratified by the presence or absence of frailty. Methods and results We examined the association between the use of ACE‐I/ARB and prognosis according to the presence [Clinical Frailty Scale (CFS) ≥ 5] or absence (CFS ≤ 4) of frailty in patients with HFpEF in a post hoc analysis of registry data. Primary endpoint was the composite of all‐cause mortality and heart failure admission. Secondary endpoints were all‐cause mortality and heart failure admission. Of 1059 patients, median age was 83 years and 45% were male. Kaplan–Meier analysis showed that the risk of composite endpoint (log‐rank P = 0.001) and all‐cause death (log‐rank P = 0.005) in patients with ACE‐I/ARB was lower in those with CFS ≥ 5, but similar between patients with and without ACE‐I/ARB in patients with CFS ≤ 4 (composite endpoint: log‐rank P = 0.830; all‐cause death: log‐rank P = 0.192). In a multivariable Cox proportional hazards model, use of ACE‐I/ARB was significantly associated with lower risk of the composite endpoint [hazard ratio (HR) = 0.52, 95% confidence interval (CI) = 0.33–0.83, P = 0.005] and heart failure admission (HR = 0.45, 95% CI = 0.25–0.83, P = 0.010) in patients with CFS ≥ 5, but not in patients with CFS ≤ 4 (composite endpoint: HR = 1.41, 95% CI = 0.99–2.02, P = 0.059; heart failure admission: HR = 1.43, 95% CI = 0.94–2.18, P = 0.091). The association between ACE‐I or ARB and prognosis did not significantly differ by CFS (CFS ≤ 4: log‐rank P = 0.562; CFS ≥ 5: log‐rank P = 0.100, for with ACE‐I vs. ARB, respectively). Adjusted HRs for CFS 1–4 were higher than 1.0 but were

Abstract Background and Aim Outcomes of an inside stent (IS, a plastic stent placed above the sphincter of Oddi) versusa self‐expandable metal stent (SEMS) for the drainage of malignant perihilar biliary obstruction has not been fully studied. The drainage strategy for perihilar biliary obstruction is difficult and should be clarified. Methods Clinical data of patients who underwent biliary drainage for malignant perihilar biliary obstruction with IS or SEMS between April 2016 and September 2021 at our institution were retrospectively examined. Outcomes, including the time to recurrent biliary obstruction (TRBO), survival, and incidence of recurrent biliary obstruction with concomitant cholangitis (RBOC), were retrospectively evaluated. Results Median TRBO was 280 (95% confidence interval [CI], 110–not available) days in the SEMS group (n = 24) and 113 (95% CI, 74–192) days in the IS group (n = 25) (P = 0.043). Among the patients with perihilar cholangiocarcinoma, the median survival of the two groups was comparable, namely 330 days in the SEMS group and 359 days in the IS group (P = 0.46). The incidence of RBOC at re‐intervention was significantly higher in patients with ISs (83.9%) than in those with SEMSs (0%) (P = 0.00004). Conclusions TRBO was significantly longer in the SEMS group. Regardless of whether SEMSs or ISs were placed during the first intervention, patient survival was similar. Using easily removable ISs first might be a reasonable option because TRBO with SEMSs was shorter than patient survival. Cholangitis is a problem associated with the placement of IS.

Abstract Background Most gastrointestinal stromal tumors (GIST) harbor a mutation in KIT or platelet‐derived growth factor receptor alfa (PDGFRA). Although genotyping is a useful predictive marker of tyrosine kinase inhibitors, whether it can predict prognosis remains controversial. Methods Data on 402 patients with GIST who underwent macroscopically complete surgery and received no neoadjuvant/adjuvant therapy were selected from a prospective GIST database at the three, participating hospitals. The types and locations of KIT and PDGFRA mutations were analyzed by direct sequencing of the amplified genes. The association between the genotypic characteristics and prognosis was then examined. Results Tumor genotypes were analyzed in 398 of 402 (99%) patients, and 120 mutation patterns were identified. KIT mutations had broad malignancy potential which differed according to the type of mutation. Deletion and deletion‐insertion type mutations were associated with worse RFS while duplication and substitution type mutations were associated with favorable RFS KIT deletion/deletion‐insertion, including codons 557 and 558, were especially associated with worse RFS on multivariate analysis both of all the patients and those with KIT mutations. Conclusions Specific GIST genotypes were significantly associated with a risk of recurrence. Genotype analysis may be useful for predicting the prognosis and determining the indications for adjuvant imatinib in patients with GIST.

Abstract Intraductal papillary neoplasms of the bile duct (IPNB) are a tumor derived from bile duct epithelium that tends to spread laterally and non‐invasively. Surgery is the first‐choice treatment for IPNB. It is extremely important to accurately diagnose the extent of lateral tumor extension. Although peroral cholangioscopy (POCS) is a potentially useful modality for detecting tumor range with direct observation, poor image quality is a limitation of POCS. Recently, a new‐generation endoscopy system (EVIS X1) was equipped with functions such as red dichromatic imaging to improve image quality. A 75‐year‐old man with cholangitis was referred to our department. Various imaging studies showed a mass in the middle to lower bile duct and dilatation of the common bile duct and the intrahepatic bile duct. Endoscopic retrograde cholangiopancreatography was performed. A biopsy of the main tumor in the lower common bile duct revealed IPNB. It was difficult to determine the extent of superficial tumor extension with modalities such as contrast‐enhanced computed tomography, magnetic resonance imaging, and endoscopic ultrasonography but the detailed evaluation was possible using POCS with red dichromatic imaging 3. The patient underwent hepatopancreatoduodenectomy. This case suggests the usefulness of direct observation using POCS with red dichromatic imaging 3 to determine the range of IPNB.

Abstract Background The outcome of catheter ablation could probably differ among patients with atrial fibrillation (AF), depending on age and AF type. We aimed to investigate the difference in predictors of outcome after catheter ablation for AF among the patient categories divided by age and AF type. Methods and Results A total of 396 patients with AF (mean age 65.69 ± 11.05 years, 111 women [28.0%]) who underwent catheter ablation from January 2018 to December 2019 were retrospectively analyzed. We divided the patients into four categories: patients with paroxysmal AF (PAF) or persistent AF (PeAF) who were 75 years or younger (≤75 years) or older than 75 years (>75 years). Kaplan–Meier survival analysis demonstrated that patients with PAF aged ≤75 years had the lowest AF recurrence among the four groups (log‐rank test, p = .0103). In the patients with PAF aged ≤75 years (N = 186, 46.7%), significant factors associated with recurrence were female sex (p = .008) and diabetes (p = .042). In the patients with PeAF aged ≤75 years (N = 142, 35.9%), the only significant factor associated with no recurrence was medication with a renin‐angiotensin system inhibitor (p = .044). In the patients with PAF aged >75 years (N = 53, 14.4%), diabetes was significantly associated with AF recurrence (p = .021). No significant parameters were found in the patients with PeAF aged >75 years (N = 15, 4.1%). Conclusions Our findings indicate that the risk factors for AF recurrence after catheter ablation differed by age and AF type.

Abstract A 64‐year‐old man with angioimmunoblastic T‐cell lymphoma (AITL) subsequently developed diffuse large B‐cell lymphoma (DLBCL) and myelodysplastic syndrome (MDS). Genomic profiling of AITL, DLBCL, and MDS samples revealed that the tumor cells from all samples shared common mutations in TET2 and DNMT3A. In addition, the IDH2 mutation was observed in AITL, and TP53 mutation was observed in DLBCL and MDS. These findings illustrate the clonal relationship between AITL and DLBCL in addition to AITL and MDS, with the latter being increasingly reported. The present findings strongly support the theory of multistep and multilineage tumorigenesis from a common founder clone.

Abstract Aims Whereas homeostasis model assessment of insulin resistance (HOMA‐IR), an easily measured but limited index of insulin resistance, has been shown to correlate with impairment of cardiac function in individuals without diabetes, the pathological relevance of insulin resistance to the development of cardiac dysfunction in individuals with type 2 diabetes has remained unclear. Here we investigated the relation between left ventricular (LV) function as assessed by echocardiography and insulin resistance as evaluated by hyperinsulinemic‐euglycemic clamp analysis, the gold standard for measurement of this parameter, in individuals with type 2 diabetes. Methods This retrospective study included 34 individuals with type 2 diabetes who underwent both hyperinsulinemic‐euglycemic clamp analysis and echocardiography. Both the insulin sensitivity index (ISI) as determined by glucose clamp analysis as well as HOMA‐IR were determined as measures of insulin resistance. The ratio of the peak early‐ to late‐diastolic mitral inflow velocities (E/A) and the LV ejection fraction (LVEF) were determined as measures of diastolic and systolic function, respectively. Results The ISI was significantly correlated with both the E/A ratio and LVEF (correlation coefficients of 0.480 and 0.360, respectively), whereas HOMA‐IR was not correlated with either cardiac parameter. Multivariate analysis revealed that ISI was an independent predictor for both a high log [E/A] (P = 0.031) and a high LVEF (P = 0.045). Conclusions Insulin resistance as evaluated by hyperinsulinemic‐euglycemic clamp analysis may be causally related to LV diastolic and systolic dysfunction in individuals with type 2 diabetes.

Abstract Aims In patients with breast cancer, skin assessment is useful for the treatment and prevention of postoperative adverse effects of radiotherapy. This study was designed to clarify the long‐term changes in the irradiated skin of patients after breast‐conserving surgery using visual inspection and noninvasive imaging. Methods We compared changes in the irradiated skin over time between evaluations, based on visual inspection and noninvasive imaging in 31 patients receiving postmastectomy radiation therapy. The condition of the skin was evaluated by visual inspection of the thermogram, and analysis of skin surface temperature, intensity of erythema, intensity of melanin, and hydration level. Results Skin surface temperature remained higher at the irradiation site after 11 months, despite the absence of erythema per visual inspection. The intensity of erythema was higher at the irradiated site until 17–19 months after completion of irradiation. Similarly, the intensity of melanin tended to be higher at the irradiated site compared with the nonirradiated site until 17–19 months. The hydration level at the irradiated site was lower at 6 months but recovered to match the nonirradiated site at 11–13 months. Impaired skin conditions assessed by noninvasive objective procedures persist longer than the assessment made by visual inspection. Conclusions Adverse effects should be treated or prevented in the long term in patients receiving postmastectomy radiation therapy.

Abstract We present a 66‐year‐old male patient with heart failure, mid‐range ejection fraction and QRS widening suffering from recurrent hospitalization due to acute heart failure. We measured intra‐cardiac pressure by cardiac catheterization to clearly demonstrate the augmentation of afterload by a vasoconstricting drug induced increase of left ventricular end‐diastolic blood pressure and pulmonary capillary wedge pressure with pulmonary arterial V‐wave augmentation (indicator of worsening of mitral regurgitation). Because the patient was considered as refractory to optimal medication, cardiac resynchronization therapy (CRT) was performed. After CRT implantation, these factors were improved, and the patient has not experienced recurrent hospitalization for >2 years.

Abstract Aims There is limited information about the clinical significance of atrial fibrillation (AF), particularly new‐onset AF, in patients with hypertrophic cardiomyopathy (HCM) in a community‐based patient cohort. This study was carried out to clarify the prevalence and prognostic impact of AF in Japanese HCM patients. Methods and results In 2004, we established a cardiomyopathy registration network in Kochi Prefecture as a prospective study, and finally, 293 patients with HCM were followed. In the patients' cohort, we recently reported the clinical outcomes including mortality and HCM‐related morbid events. HCM‐related adverse cardiovascular events were defined in the following: (i) sudden cardiac death (SCD)‐relevant events including SCD, spontaneous sustained ventricular tachycardia, and appropriate implantable cardioverter defibrillator discharge; (ii) heart failure (HF) events with the composite of HF death and hospitalization for HF; and (iii) embolic events included embolic stroke‐related death and admission for embolic events. In the present study, we focused on AF and conducted a detailed investigation. At registration, the mean age of the patients was 63 ± 14 years, and 86 patients (29%) had documented AF including paroxysmal AF. Patients with AF at registration were characterized by worse clinical profiles including more advanced age, more symptomatic, more advanced left ventricular, and left atrial remodelling at registration. During a mean follow‐up period of 6.1 ± 3.2 years, a total of 77 HCM‐related adverse events occurred, and the presence of AF at registration was associated with an increased risk of HCM‐related adverse events, particularly heart failure events. During the follow‐up period, an additional 31 patients (11%) had documentation of AF for the first time, defined as new‐onset AF, with an annual incidence of approximately 1.8%, and finally, a total of 117 patients (40%) showed AF. The presence of palpitation and enlarged left atrial diameter, particularly left atrial diameter ≥50 mm, at registration were significant predictors of new‐onset AF. Importantly, the incidence of overall HCM‐related adverse events was further higher in patients with new‐onset AF observed from AF onset than in patients with AF at registration. Conclusions In our HCM registry in an aged Japanese community, a significant proportion developed AF. The presence of AF, particularly new‐onset AF, was associated with increased incidence of HCM‐related events. AF may not be just a marker of disease stage but an important trigger of adverse events.

Abstract This paper clarifies the changes in kampungs and their houses (rumah kampungs) over the past 35 years based on field surveys of three kampungs in Surabaya, Indonesia, conducted in 1983/84, 2006, and 2016–2018. The major objective is to develop new policies for the Kampung Improvement Program (KIP) and public housing. The main finding is that most of the kampungs have maintained their basic spatial structure and community organization, although the houses themselves have been transformed. Thus, kampungs in Surabaya continue to maintain their unique characteristics.

Abstract Purpose To evaluate clinical outcomes after endometrial receptivity analysis (ERA). Methods This was a multicenter, retrospective cohort study involving 861 women who underwent ERA testing at certified fertility clinics in Japan, and who received subsequent personalized blastocyst embryo transfers (ET) between 2018 and 2020. Clinical outcomes, including pregnancies, miscarriages, and live births, were evaluated according to receptivity status for ERA. Results Mean patient age was 37.7 years (SD = 4.0), and the median number of previous ETs was 2 (interquartile range, 2–3). 41.0% (353/861) of patients were non‐receptive for ERA testing. Clinical pregnancy, miscarriage, and live birth rates for personalized blastocyst ET were 44.5% (226/508), 26.1% (59/226), and 26.8% (136/508) for receptive patients, and 43.1% (152/353), 28.3% (43/152), and 28.9% (102/353) for non‐receptive patients, all statistically nonsignificant. Multiple logistic regression demonstrated similar nonsignificant associations between receptivity and clinical outcomes. Greater patient age, smoking, and longer duration of infertility were significantly and negatively associated with receptivity, whereas a history of delivery was positively associated and statistically significant. Conclusions Clinical outcomes after ERA testing were similar between receptive and non‐receptive patients. Further prospective study including an appropriate comparison group are warranted to evaluate the efficacy of ERA testing.

Abstract Aim Osteoporosis in patients after gastrectomy is increasing with the aging of gastric cancer patients. Bisphosphonates are effective treatments for osteoporosis; however, their safety or efficacy in postgastrectomy patients has not been established. The purpose of this multicenter prospective intervention study was to investigate the impact of monthly minodronate on osteoporosis after gastrectomy. Methods Of the 261 enrolled gastric cancer patients, 164 patients were diagnosed with osteoporosis based on criteria of the Japan Society of Osteoporosis. They were randomly assigned 1:1 to groups treated with active vitamin D (VD group) or monthly minodronate (MIN group). The primary endpoint was changes in lumbar bone mineral density (L‐BMD) 12 mo after the start of administration. The secondary endpoints were changes in bone metabolism markers, adverse events (AEs), or treatment completion rates. Results There was no significant difference in patient background between the VD (n = 82) and MIN (n = 82) groups. In the MIN group, the increase in L‐BMD was significantly higher than that in the VD group (4.52% vs 1.72%, P = .001), with a significant reduction in bone metabolism markers; blood NTX (−25.6% vs −1.6%, P

ABSTRACT Heterozygous RFX6 mutation has emerged as a potential cause of maturity‐onset diabetes mellitus of the young (MODY). A 16‐year‐old female was diagnosed with diabetes by her family doctor and was referred to our institution for genetic examination. Genetic testing revealed a novel RFX6 heterozygous mutation (NM_173560: exon17: c.1954C>T: p.R652X) in the patient and in her mother and brother. She had no islet‐specific autoantibodies and showed a reduced meal‐induced response of insulin, glucose‐dependent insulinotropic polypeptide, and glucagon‐like peptide‐1, which is consistent with the phenotype of MODY due to heterozygous RFX6 mutation. In conclusion, we report a case of MODY due to a novel heterozygous mutation, p.R652X.

Abstract Adverse reactions, including the onset of diabetes, after coronavirus disease 2019 (COVID‐19) vaccination have been reported. Herein, we report a case of a man who developed anti‐glutamic acid decarboxylase (GAD) antibody‐positive fulminant type 1 diabetes 15 weeks after COVID‐19 vaccination, atypical of the previously reported anti‐GAD antibody‐negative cases.

Abstract Aims Frailty is associated with prognosis of cardiovascular diseases. However, the significance of frailty in patients with heart failure with preserved ejection fraction (HFpEF) remains to be elucidated. The purpose of this study was to examine the prognostic significance of the Clinical Frailty Scale (CFS) in real‐world patients with HFpEF using data from a prospective multicentre observational study of patients with HFpEF (PURSUIT‐HFpEF study). Method and Results We classified 842 patients with HFpEF enrolled in the PURSUIT‐HFpEF study into two groups using CFS. The registry enrolled patients hospitalized with a diagnosis of decompensated heart failure. Median age was 82 [interquartile range: 77, 87], and 45% of the patients were male. Of 842 patients, 406 were classified as high CFS (CFS ≥ 4, 48%) and 436 as low CFS (CFS ≤ 3, 52%). The primary endpoint was the composite of all‐cause mortality and heart failure admission. Secondary endpoints were all‐cause mortality and heart failure admission. Patients with high CFS were older (85 vs. 79 years, P

Abstract Aims/Introduction Glucose fluctuation (GF) is a residual risk factor for coronary artery disease (CAD). We investigated whether GF influenced clinical outcomes and progression of coronary stenosis in stable CAD patients. Materials and Methods In this prospective study, 101 consecutive lipid‐controlled stable CAD patients underwent percutaneous coronary intervention were enrolled, and GF was expressed as the mean amplitude of glycemic excursion (MAGE) obtained by continuous glucose monitoring before the procedure was evaluated. At 9 months after enrollment, culprit and non‐culprit (mild‐to‐moderate stenosis without ischemia) lesions were serially assessed by angiography. Cardiovascular events (CVE) consisting of cardiovascular death, non‐fatal myocardial infarction or ischemia‐driven revascularization during 2‐year follow up, rapid progression in non‐culprit lesions (defined as ≥10% luminal narrowing progression in lesions with stenosis ≥50%, ≥30% luminal narrowing progression in non‐culprit lesions with stenosis

Abstract Background Nivolumab is a second‐line chemotherapy for non‐small cell lung cancer (NSCLC). This study explored the impact of clinical biomarkers such as neutrophil:lymphocyte ratio (NLR), C‐reactive protein:albumin ratio (CAR), and modified Glasgow prognostic score on the efficacy and outcome of nivolumab monotherapy in previously treated NSCLC patients. Methods We retrospectively analyzed advanced or postoperative recurrence of NSCLC in 113 patients in two Japanese facilities from January 2015 to December 2019. Optimal cutoff values of NLR and CAR were assessed by the area under the receiver operating characteristic curves predicting death events to conduct regression analysis. Baseline values and values collected eight weeks after nivolumab treatment were measured to investigate time‐series changes of these markers. Results The patients showed median overall survival (OS) and progression‐free survival (PFS) of 14.0 months and 2.3 months, respectively, with both being significantly longer in patients with partial response (PR) than in patients with progressive disease (PD). Optimal cutoff levels for NLR and CAR were 5.8 and 0.83, with significant decrease in CAR (P = 0.002) from baseline levels in PR patients and significant increase in PD patients. Baseline CAR ≥0.83 was significantly associated with one‐year mortality events and overall survival (OS), and multivariate analysis showed significant association of age ≤70 years, an Eastern Cooperative Oncology Group performance status score of 2 or 3, and a baseline CAR ≥0.83 with inferior OS. Conclusions For second‐line nivolumab therapy, evaluation of baseline CAR and subsequent changes in CAR may be predictive of therapeutic response to nivolumab and long‐term survival in NSCLC patients. Key points Significant findings of the study The baseline value of C‐reactive protein:albumin ratio was significantly associated with one‐year mortality and overall survival in non‐small cell lung cancer patients treated with nivolumab. What this study adds Time‐series change of C‐reactive protein:albumin ratio may be useful for predicting the treatment efficacy in patients treated with nivolumab.

Background Modification of arrhythmogenic substrates with extensive ablation comprising linear and/or complex fractional atrial electrogram ablation in addition to pulmonary vein isolation (PVI‐plus) can theoretically reduce the recurrence of atrial fibrillation. The DR‐FLASH score (score based on diabetes mellitus, renal dysfunction, persistent form of atrial fibrillation, left atrialdiameter >45 mm, age >65 years, female sex, and hypertension) is reportedly useful for identifying patients with arrhythmogenic substrates. We hypothesized that, in patients with persistent atrial fibrillation, the DR‐FLASH score can be used to classify patients into those who require PVI‐plus and those for whom a PVI‐only strategy is sufficient. Methods and Results This study is a post hoc subanalysis of the a multicenter, randomized controlled, noninferiority trial investigating efficacy and safety of pulmonary vein isolation alone for recurrence prevention compared with extensive ablation in patients with persistent atrial fibrillation (EARNEST‐PVI trial). This analysis focuses on the relationship between DR‐FLASH score and the efficacy of different ablation strategies. We divided the population into 2 groups based on a DR‐FLASH score of 3 points. A total of 469 patients were analyzed. Among those with a DR‐FLASH score >3 (N=279), the event rate of atrial arrhythmia recurrence was significantly lower in the PVI‐plus arm than in the PVI‐only arm (hazard ratio [HR], 0.45 [95% CI, 0.28–0.72]; P3 and DR‐FLASH score ≤3 (P value for interaction=0.020). Conclusions The DR‐FLASH score is a useful tool for deciding the catheter ablation strategy for patients with persistent atrial fibrillation. Registration URL: https://clinicaltrials.gov; Unique identifier: NCT03514693.