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ABSTRACT Background The Asian Working Group for Cachexia (AWGC) proposed a new definition of cachexia; however, its impact on cachexia prevalence and overlaps with other conditions, such as sarcopenia and malnutrition, are unclear. We investigated these aspects and the prognostic value of cachexia based on the AWGC on mortality in older patients with heart failure (HF). Methods This study was a secondary analysis of a prospective multicentre cohort, namely, the FRAGILE‐HF cohort study. Older (≥ 65 years) patients who had been hospitalized due to decompensated HF were enrolled. We assessed the presence/absence of cachexia based on the AWGC and Evans' criteria. Sarcopenia and malnutrition based on the Asian Working Group for Sarcopenia 2014 and the Global Leadership Initiative on Malnutrition criteria were also assessed to compare their prevalence and the overlaps between them. Patients were stratified in relation to the presence/absence of cachexia based on the AWGC criteria, and their mortality rates were compared. Results Of the 861 enrolled patients (median [interquartile range] age, 80 years [73–85 years]; male, 58.9%), cachexia, as evaluated based on the AWGC and Evans' criteria, sarcopenia and malnutrition, was present in 74.1%, 36.2%, 20.6% and 55.2% of patients, respectively. AWGC‐defined cachexia was most common in the four conditions. All‐cause death events occurred in 153 (18.1%) patients in 2 years. AWGC‐defined cachexia (adjusted hazard ratio [aHRs], 1.442; 95% confidence interval [95% CI], 0.931–2.233; p = 0.101) was not associated with all‐cause mortality in older patients with HF after adjusting for other HF prognosis factors, such as the B‐type natriuretic peptide and the Meta‐Analysis Global Group in Chronic risk score, whereas cachexia evaluated based on Evans's criteria (aHRs, 1.547; 95% CI, 1.118–2.141; p = 0.009), sarcopenia (aHRs, 1.737; 95% CI, 1.214–2.485; p = 0.003), and malnutrition (aHRs, 1.581; 95% CI, 1.094–2.284; p = 0.015) was associated with all‐cause mortality. Conclusions Three‐quarters of older patients with HF had cachexia as evaluated by the AWGC criteria, and this was not associated with a worse prognosis. As the new AWGC cachexia criteria will result in a significantly larger proportion of patients being diagnosed with cachexia, the implementation of the criteria in clinical practice requires further consideration. Trial Registration: UMIN‐CTR unique identifier: UMIN000023929

Abstract Aims In heart failure (HF), inflammation is linked to malnutrition and impaired physical function. In this study, we aimed to assess how novel nutritional–inflammatory markers and lymphocyte‐to‐C‐reactive protein ratio (LCR) and score (LCS) are associated with the nutritional status, physical function, and prognosis of patients with HF. Methods and results This study was a secondary analysis of the FRAGILE‐HF study, a prospective observational study conducted across 15 hospitals in Japan. We included 1212 patients (mean age, 80.2 ± 7.8 years; 513 women) hospitalized with HF, who were classified into three groups according to their LCS score: 0 (n = 498), 1 (n = 533), and 2 (n = 181). Baseline data on physical examination, echocardiography, blood test results (including lymphocyte counts and CRP levels), and oral medication usage were collected in a clinically compensated state before discharge. Nutritional status and physical function were evaluated using several indices and tests. The primary outcome of this study was all‐cause death within 2 years. Univariate and multivariate linear regression analyses were performed to evaluate the associations among the nutritional status, physical function, and LCR/LCS. Patients with an LCS score of 2 were older and had a lower body mass index than those in the other two groups. Multivariate linear regression analysis revealed that lower LCR and higher LCS were independently associated with worse nutritional status, lower handgrip strength, shorter physical performance battery score, and shorter 6‐min walk distance. At 2 years, all‐cause death occurred in 254 patients: 86 (17.6%), 113 (21.5%), and 55 (30.9%) with LCS scores of 0, 1, and 2, respectively (P = 0.001). Cox proportional hazards analysis revealed that LCR and LCS were significantly associated with 2‐year mortality even after adjusting for the conventional risk model (LCS score, 0 vs. 2: hazard ratio, 1.64; 95% confidence interval [CI]; 1.14–2.35; P = 0.007; log‐transformed LCR: hazard ratio, 0.88; 95% CI, 0.81–0.95; P = 0.002). LCR yielded additional prognostic predictability compared with the conventional risk model (continuous net reclassification improvement, 0.153; 95% CI, 0.007–0.299; P = 0.041). Conclusions LCR and LCS emerge as potential predictors of nutritional status, physical function, and prognosis in older patients with HF.

Abstract Aims Knowing the upper time limit for successful weaning from temporary mechanical circulatory support in cardiogenic shock will help with decision‐making regarding advanced heart failure (HF) therapy or considering withdrawal of care. The aim of this study was to investigate the association between the support duration and successful weaning from veno‐arterial extracorporeal membrane oxygenation (VA‐ECMO) in patients with cardiogenic shock. Methods and results A retrospective single‐centre cohort study was conducted between January 2013 and June 2023. It included 100 consecutive patients with cardiogenic shock who were treated with VA‐ECMO. Patients with out‐of‐hospital cardiac arrest were excluded. The primary outcome was successful weaning from VA‐ECMO (i.e., VA‐ECMO decannulation and survival to discharge). The association between the length of support duration and the weaning success rate was analysed. Patients were divided into three groups according to ECMO support duration: Group A (≤7 days), Group B (8–14 days), and Group C (≥15 days). Multivariable logistic regression analysis was used to evaluate the impact of the length of support duration on successful weaning of VA‐ECMO. The median age was 67 years, and 73% of study participants were male. The underlying aetiologies of cardiogenic shock were as follows: acute myocardial infarction, 50; fulminant myocarditis, 19; cardiomyopathy, 15; valvular heart disease, 8; and other, 8. Seventy‐five patients (75%) were attempted to wean VA‐ECMO, and 67 moved on to decannulation. In total, 43 (43%) patients were successfully weaned from VA‐ECMO. The median length of ECMO support duration was 8 [3–15] days. Compared with those who underwent successful ECMO decannulation, those who did not had a significantly longer support duration of VA‐ECMO (5 [3–9] days vs. 12 [3–22] days, P = 0.004). The weaning success rate was significantly higher in patients with short support duration; 58% (29/50), 40% (10/25), 16% (4/25) in Groups A, B, and C, respectively (P = 0.002). Overall, none of the patients supported for over 24 days (0/11) were successfully weaned from VA‐ECMO. On multivariable logistic regression analysis, the length of support duration was independently associated with successful weaning after adjusting for age, sex, underlying aetiology, and left ventricular ejection fraction (odds ratio, 0.813 [per 3 days]; 95% confidence interval, 0.679–0.914; P = 0.025). Conclusions Long support duration of VA‐ECMO was significantly associated with a low rate of successful weaning in patients with cardiogenic shock. Patients who require VA‐ECMO for over 1 week should start considering advanced HF therapy or withdrawal of care.

Abstract Aims Mitral stenosis (MS) occasionally coexists with aortic stenosis (AS). Limited data are available regarding the functional class and clinical outcomes of patients who undergo transcatheter aortic valve implantation (TAVI) for combined AS and MS. This study compared the clinical outcomes in patients with and without MS who underwent TAVI for severe AS and assessed the impact of mitral annulus calcification (MAC) severity, transmitral gradient (TMG) and mitral valve area (MVA) on outcomes in patients with combined AS and MS. Methods We investigated patients in the OCEAN‐TAVI registry who underwent TAVI. MS was defined as an MVA ≤ 1.5 cm2 or TMG ≥ 5 mmHg. The composite of all‐cause death and admission for heart failure was compared between patients with and without MS. The impact of MAC, TMG and MVA on outcomes was assessed in patients with combined AS and MS. Results We identified 106 patients with MS (MAC 84%; TMG 6.4 ± 2.6 mmHg; MVA 1.10 ± 0.31 cm2) and 6570 without MS as controls. The MS group was older (85 ± 5 vs. 84 ± 5 years, P = 0.033), more of women (85 vs. 67%, P

Abstract Aims Left atrial (LA) volume index (LAVI) in chronic heart failure (HF) predicts cardiovascular outcomes. However, the association between LAVI reduction during acute decompensated HF (ADHF) and its prognostic potential is limited. We hypothesized that LA reverse remodelling (LARR) after ADHF therapy would be associated with better clinical outcomes. Methods This retrospective study analysed clinical outcomes and the LAVI reduction rate of 363 out of 861 patients hospitalized for ADHF who underwent two‐point echocardiography at admission and discharge between January 2015 and December 2019. The mean age was 74.3 ± 13.6 years, and the mean ejection fraction (EF) was 38.9 ± 15.2%. The follow‐up echocardiogram was performed 13.0 [9.5, 20] days after admission. As the median LAVI reduction rate was 7.02%, the LARR was defined as an LAVI reduction rate >7%. Results During the 34.0 ± 20.2 months of follow‐up, 117 patients (32.2%) reached the primary endpoint defined as cardiovascular death and rehospitalization for ADHF. Kaplan–Meier survival analysis showed that patients with LARR had a better prognosis. Multivariate analysis indicated that LARR was an independent predictor of cardiovascular events. Similar findings were observed in the subgroup analyses of patients with persistent/permanent atrial fibrillation and those with non‐HF with reduced EF. Among patients who were brain natriuretic peptide (BNP) responders, defined as a relative reduction of >70% in BNP from admission to discharge, non‐LARR was observed in 41.6%. BNP responders without LARR experienced worse prognoses. Conclusions LARR in the early vulnerable phase after hospitalization for ADHF was associated with better long‐term clinical outcomes.

ABSTRACT Aim Nocturia impairs the quality of life in patients with type 2 diabetes mellitus. Although sodium glucose co‐transporter 2 inhibitors (SGLT2i) such as tofogliflozin increase urine volume, their impact on nocturia, in conjunction with dietary salt restriction, is less clear. Materials and Methods This multicenter, open‐label, randomized, parallel‐group trial included 80 subjects with type 2 diabetes and nocturia. The patients were divided into two groups: one receiving tofogliflozin, the shortest half‐life, without salt restriction, and the other receiving both tofogliflozin and dietary salt restriction. The primary endpoint was nocturia frequency at 12 weeks. The secondary outcomes included changes in daytime urination frequency, urine volume, and home blood pressure. Results At 12 weeks, there were no significant differences in nocturia changes between both groups. Nocturia frequency did not change in the tofogliflozin without salt restriction group from 1.5 ± 0.8 to 1.3 ± 1.1 times per night (P = 0.297), and significantly decreased from 1.6 ± 1.0 to 1.3 ± 0.7 times per night in the tofogliflozin and dietary salt restriction group (P = 0.049). There was a trend toward increased urine volume and frequency during the daytime in the group with salt restriction, indicating a time‐shift effect of the short half‐life tofogliflozin and salt restriction on urinary time. Conclusions The frequency of nocturia after tofogliflozin did not increase. Tofogliflozin reduced nocturia when combined with salt restriction. Furthermore, daytime urine volume and frequency showed an increasing trend, suggesting a shift in urine production to daytime hours due to the short half‐life of tofogliflozin. Dietary modifications can enhance the therapeutic benefits of tofogliflozin in managing nocturia in people with type 2 diabetes.

ABSTRACT Aims/Introduction We previously showed that glucokinase haploinsufficiency improves the glucose tolerance of db/db mice by preserving pancreatic β‐cell mass and function. In the present study, we aimed to determine the effects of glucokinase haploinsufficiency on the β‐cell mass and function of long‐term high‐fat, high‐sucrose (HFHS) diet‐fed mice. Materials and Methods Four‐week‐old male glucokinase haploinsufficient (Gck+/−) mice and 4‐week‐old male wild‐type (Gck+/+) mice (controls) were each divided into two groups: an HFHS diet‐fed group and a normal chow‐fed group, and the four groups were followed until 16, 40 or 60 weeks‐of‐age. Their glucose tolerance, glucose‐stimulated insulin secretion and β‐cell mass were evaluated. In addition, islets were isolated from 40‐week‐old mice, and the expression of key genes was compared. Results Gck+/−HFHS mice had smaller compensatory increases in β‐cell mass and glucose‐stimulated insulin secretion than Gck+/+HFHS mice, and their glucose tolerance deteriorated from 16 to 40 weeks‐of‐age. However, their β‐cell mass and glucose‐stimulated insulin secretion did not decrease between 40 and 60 weeks‐of‐age, but rather, tended to increase, and there was no progressive deterioration in glucose tolerance. The expression of Aldh1a3 in pancreatic islets, which is high in several models of diabetes and is associated with an impairment in β‐cell function, was high in Gck+/+HFHS mice, but not in Gck+/−HFHS mice. Conclusions Glucokinase haploinsufficiency prevents the progressive deterioration of pancreatic β‐cell mass/function and glucose tolerance in long‐term HFHS diet‐fed mice.

ABSTRACT Aims/Introduction The 2023 Delphi consensus recommended the use of new term, metabolic dysfunction‐associated steatotic liver disease (MASLD), aiming conceptual shift from the conventional non‐alcoholic fatty liver disease (NAFLD). The association between NAFLD and type 2 diabetes mellitus (T2DM) development is well known. This study aimed to examine the correlation between MASLD and T2DM development, comparing their utility as predictors. Materials and Methods This retrospective cohort study obtained data from a medical health checkup program conducted at Asahi University Hospital, Japan, between 2004 and 2021. Logistic regression analysis was used to assess the association between MASLD and incident T2DM over 5 years. To compare the predictive utility of NAFLD and MASLD, receiver operating characteristic curves were drawn, followed by area under the curve (AUC) comparisons. Results In total, 15,039 participants (59.6% males; median [interquartile range {IQR}] age, 44 [38, 50] years) were included. Out of 2,682 participants meeting the criteria for MASLD, 234 individuals (8.7%) developed T2DM. Multivariate analysis revealed a significantly elevated risk of T2DM in MASLD compared with the reference healthy group (without steatotic liver disease or cardiometabolic risk), presenting an OR of 127.00 (95% CI 40.40–399.00, P

ABSTRACT Aims Despite the reported success of low‐carbohydrate diets in improving glycemic control in the Western countries, no studies have investigated the effects of such diets in Asians. We aimed to conduct a systematic review and meta‐analysis of randomized controlled trials to examine the effects of low‐carbohydrate diets on glycemic control in East Asian adults. Materials and Methods We systematically searched the PubMed, Cochrane Library, and Embase databases from inception to June 28, 2023, to identify randomized controlled trials examining the efficacy of low‐carbohydrate diets in patients with type 2 diabetes (PROSPERO number CRD 42023453007). The primary outcome was the difference in glycated hemoglobin levels between the low‐carbohydrate diet and control groups. The secondary outcome was the difference in body mass index, fasting blood glucose level, blood pressure, and lipid profile. Results Six randomized controlled trials met the eligibility criteria. The study duration ranged from 3 to 18 months, with five studies conducted within 6 months. The results showed that low‐carbohydrate diets were more beneficial in lowering glycated hemoglobin levels and body mass index than control diets. The risk of bias for the six studies was minimal for two and moderate for four. The heterogeneity among the studies was low. Conclusions Low‐carbohydrate diets improved glycated hemoglobin levels and body mass index in East Asians compared with control diets. Therefore, carbohydrate restriction may be effective for glycemic management in East Asians with type 2 diabetes for at least 6 months.

The TGF‐β superfamily plays a pivotal role in the regulation of adipogenesis, but little is known about the potential differential role of the three isoforms of TGF‐β, TGF‐β‐1~3. To further elucidate their role, two‐dimensionally (2D) and three‐dimensionally (3D) cultured 3T3‐L1 mouse preadipocytes were subjected to the following analyses: (a) qPCR analysis of adipogenesis‐related factors and major extracellular matrix protein (2D and /or 3D), (b) lipid staining by Oil Red O (2D) or BODIPY (3D), (c) Seahorse cellular metabolic measurement (2D), and (d) size and stiffness measurements of 3D 3T3‐L1 spheroids. In the 2D cultured 3T3‐L1 cells, mRNA expression levels of adipogenesis‐related genes and Oil Red O lipid staining intensity were significantly increased by adipogenesis and they were substantially decreased following treatment with 0.1 nm TGF‐β isoforms, with TGF‐β2 having the greater effects. Consistent with these results, treatment with TGF‐β2 resulted in suppression of mitochondrial and glycolytic functions in 2D cultured 3T3‐L1 cells. However, the inhibitory effect of TGF‐β on adipogenesis decreased under 3D spheroid culture conditions and TGF‐β isoforms did not affect adipogenesis‐induced (a) enlargement and downsizing of 3T3‐L1 spheroids, (b) increase in BODIPY lipid staining intensity, and (c) up‐regulation of the mRNA expression of adipogenesis‐related genes. The findings presented herein suggest that the three TGF‐β isoforms have different suppressive effects on adipogenesis‐related cellular properties of 2D cultured 3T3‐L1 cells and that their effects decrease under 3D spheroid culture conditions.

Abstract Aim Overweight is associated with low‐grade systemic inflammation. However, its effect on neuroinflammation remains unclear. We examined the possible association between overweight and neuroinflammation using cerebrospinal fluid (CSF) in a nonclinical adult population in Japan. Methods CSF and plasma levels of interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), tumor necrosis factor‐α (TNF‐α), plasma levels of C‐reactive protein (CRP), and leptin were measured in nonclinical adult participants (35 males and 34 females) who had no current or past history of neuropsychiatric diseases. We performed partial correlation analyses with sex and age as covariates between the body mass index (BMI) and the inflammatory markers and compared them between overweight and nonoverweight participants. Results The BMI significantly correlated with CSF levels of IL‐6 (rs = 0.32, p = 0.009), plasma levels of CRP (rs = 0.30, p = 0.016), IL‐1β (rs = 0.29, p = 0.019), IL‐6 (rs = 0.25, p = 0.042), TNF‐α (rs = 0.43, p

Abstract Background We investigated the clinical outcomes of involved‐field high‐dose (≥66 Gy) chemoradiotherapy (CRT) combined with respiratory motion management for esophageal squamous cell carcinoma (ESCC). Methods Patients who underwent definitive CRT for histologically confirmed ESCC in our department between 2012 and 2018 were retrospectively analyzed. Respiratory motion management strategies included breath‐holding (63%) and mask immobilization (29%) based on individual measurements of respiratory tumor motion using radiographic fluoroscopy with endoscopically placed clip markers as landmarks. We evaluated patient characteristics, treatment efficacy, failure patterns, and toxicities. Results We enrolled 35 patients with a prescribed dose of 66–70 Gy in 33–35 fractions. The overall response rate within 6 months post‐CRT was 94.3%; the median follow‐up period for survivors was 43 months. The 2‐year overall survival (OS), progression‐free survival, and locoregional failure‐free survival rates were 51.4%, 42.9%, and 42.9%, respectively. A significant difference in OS was observed between patients with and without esophageal fistulas after CRT (p = 0.002, log‐rank test). Disease failure occurred in 16 patients (45.7%), including one (2.9%) with out‐of‐field regional nodal failure. Major grade 3 or higher toxicities included decreased white blood cell count (48.6%), neutrophil count (34.3%), and esophageal stenosis (31.4%). No grade 3 or higher cardiopulmonary toxicities were observed. Bronchial/tracheal tumor compression and a higher radiotherapy dose (70 Gy) were significantly correlated with esophageal fistulas. Conclusion Involved‐field high‐dose CRT with respiratory motion management may be a feasible treatment option for ESCC. However, a comprehensive assessment of esophageal fistula risk is required to identify suitable candidates.

Abstract Aims/Introduction The clinical significance of age‐related biomarkers in patients with diabetes has not been fully elucidated. In this study, we aimed to establish models to predict the progression of aging in patients with diabetes using biomarkers. Materials and Methods This single‐center, retrospective cohort study included 115 Japanese patients with diabetes aged ≥60 years. Age‐related adverse health outcomes were defined as emergency hospitalization, any increase in the level of nursing care certification, admission to a nursing home or death. The associations of age‐related biomarker levels (adiponectin, growth differentiation factor 15 [GDF15], C‐X‐C motif chemokine ligand 9 and apelin) and clinical indicators with age‐related adverse health outcomes were evaluated. Factors that predominantly influenced the occurrence of age‐related adverse health outcomes were explored using the Cox proportional hazards model. Results The mean age of the 115 participants was 73 years, 50.6% were men, the mean body mass index and hemoglobin A1c level were 25.3 kg/m2 and 9.79%, respectively. There were 26 age‐related adverse health outcomes during the study period (median 1.93, range 0–4.65 years). In a model combining clinical indicators and biomarkers, including the Barthel Index, GDF15 and adiponectin, the occurrence of age‐related adverse health outcomes was found to be significantly associated with GDF15 and Barthel Index. The group with both GDF15 and adiponectin levels higher than the median proved to be significantly higher than the group with both lower. Conclusions The measurement of GDF15 and adiponectin levels and the Barthel Index might be useful for predicting age‐related adverse health outcomes in patients with diabetes.

Introduction Horseshoe kidney is characterized by midline fusion of the lower poles of both kidneys. We report a case where robot‐assisted pyeloplasty was performed for hydronephrosis complicating horseshoe kidney. Case presentation A 31‐year‐old man repeatedly developed fever since childhood. He visited a local clinic for fever and left back pain, where he was diagnosed and treated for acute pyelonephritis. Abdominal computed tomography led to a diagnosis of horseshoe kidney and associated left ureteropelvic junction obstruction. He was referred to our hospital for pyeloplasty because of persistent left back pain. Robot‐assisted left pyeloplasty was performed using the Anderson–Hynes technique with four ports because crossing vessels were discovered intraoperatively. Isthmusectomy was not performed. The postoperative course was favorable. Computed tomography performed approximately 2 years post‐surgery showed improvement in hydronephrosis. No left back pain was reported. Conclusion Our case experience suggests the utility of robot‐assisted pyeloplasty for patients with horseshoe kidney.

Introduction A retroperitoneoscopic procedure for bladder neck closure has not yet been described. Case presentation Case 1 was a 56‐year‐old man who underwent clean intermittent catheterization for spastic paraplegia due to a thoracic spinal cord injury 37 years prior. Case 2 was an 80‐year‐old bedridden woman who underwent urethral catheterization after a femoral fracture and brain infarction 3 years prior. Both patients presented with Fournier's gangrene, and the urogenital region, including the necrotic urethra, was debrided. Although a permanent suprapubic catheter was established, postoperative wound healing was poor owing to continuous urine leakage from the urethral stump. Therefore, we performed retroperitoneoscopic bladder neck closure, and the urinary incontinence was completely resolved. Conclusion Retroperitoneoscopic bladder neck closure is a feasible and less invasive procedure for treating continuous urinary incontinence from the urethral stump in patients with Fournier's gangrene after surgical debridement and having a permanent suprapubic catheter.

Abstract Background The distribution of anti‐factor Xa activity (AXA) in patients with nonvalvular atrial fibrillation (NVAF) taking edoxaban 15 mg has not been fully elucidated. Methods and Results The trough and peak AXA were measured in 19 NVAF patients taking edoxaban 15 mg. We compared these results with those in patients taking edoxaban 30 mg. The peak AXA differed significantly between the 15 mg and the 30 mg groups (0.74 ± 0.40 IU/mL vs. 1.25 ± 0.48 IU/mL, respectively; p

Abstract Local ensemble transform Kalman filter (LETKF)‐based Ocean Research Analysis (LORA) version 1.0 datasets for western North Pacific (WNP) and Maritime Continent (MC) regions (LORA‐WNP and ‐MC, respectively) are released through the JAXA‐RIKEN Ocean Analysis website. The LORA datasets are created using an eddy‐resolving LETKF‐based ocean data assimilation system with satellite sea‐surface temperature, salinity, and height data and with in‐situ temperature and salinity data assimilated daily. The LORA datasets include 128‐member ensemble analyses at the sea surface (2D), each term of mixed‐layer temperature and salinity budget equations, and the related variables (2D) such as mixed‐layer depth and heat and freshwater fluxes as well as system grid information and analysis ensemble mean and spread (3D), from August 2015 to January 2024 (as of June 2024). The LORA datasets are useful for geoscience research and practical applications, especially for particle tracking, boundary conditions of atmospheric models, and research on spatiotemporal variations in sea‐surface temperature and salinity.

ABSTRACT Aims/Introduction Efficacy of long‐term low‐carbohydrate diets (LCD) to improve glycemic management for type 2 diabetes remains controversial. Thus, we investigated the association between long‐term LCD and glycemic control in individuals with type 2 diabetes. Materials and Methods We searched PubMed, Embase and the Cochrane Database for articles published up to June 2023, and included randomized controlled trials conducted on LCD interventions for >12 months in adults with type 2 diabetes. Primary outcome was the difference in glycated hemoglobin between long‐term LCD and control groups. Additionally, we evaluated the differences in changes in systolic and diastolic blood pressure, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, triglyceride, and weight between long‐term LCD and control groups. Results Six studies were identified and met the inclusion criteria. This study did not show significant differences in changes in glycated hemoglobin between long‐term LCD and control diets (standardized mean difference −0.11, 95% confidence interval −0.33 to 0.11, P = 0.32). As with glycemic control, there were no significant differences in the changes in weight loss, blood pressure, and low‐density lipoprotein cholesterol between long‐term LCD and control diets. However, long‐term LCD were associated with greater elevation in high‐density lipoprotein cholesterol (standardized mean difference 0.22, 95% confidence interval 0.04–0.41; P = 0.02) and decrease in triglyceride (standardized mean difference −0.19; 95% confidence interval −0.37 to 0.02; P = 0.03) than that in control diets. Conclusions Our findings suggest efficacy of long‐term LCD in treating dyslipidemia in individuals with type 2 diabetes, but do not recommend long‐term LCD for glycemic control in the individuals.

Abstract Aims Atrial fibrillation (AF) is frequently associated with heart failure with preserved ejection fraction (HFpEF), but the diagnosis and prediction of the outcomes of HFpEF are difficult. Notably, the Heart Failure Association of the European Society of Cardiology proposed the use of the HFA–PEFF score in the diagnosis of HFpEF. This study aimed to assess the prognostic value of the pre‐ and post‐procedural HFA–PEFF scores in patients with preserved ejection fraction (EF) after catheter ablation (CA) for AF. The primary endpoint was a composite of cardiac hospitalization for cardiovascular events and all‐cause mortality. The secondary endpoint was AF recurrence. Methods and results Overall, 354 patients with AF and preserved EF who underwent CA as well as blood tests and transthoracic echocardiography 2 weeks before and 6 months after CA from January 2018 to December 2019 were retrospectively enrolled in the study. In the 354 participants, univariate analysis showed that the post‐procedural HFA–PEFF score was associated with a 3‐year risk of the primary endpoint (hazard ratio [HR] = 3.73; 95% confidence interval [CI] = 2.07–6.73; P

ABSTRACT Aims The utilization of long‐term effect of internet of things (IoT) on glycemic control is controversial. This trial aimed to examine the effect of an IoT‐based approach for type 2 diabetes. Materials and Methods This randomized controlled trial enrolled 1,159 adults aged 20–74 years with type 2 diabetes with a HbA1c of 6.0–8.9% (42–74 mmol/mol), who were using a smartphone on a daily basis were randomly assigned to either the IoT‐based approach group (ITG) or the control group (CTG). The ITG were supervised to utilize an IoT automated system that demonstrates a summary of lifelogging data (weight, blood pressure, and physical activities) and provides feedback messages that promote behavioral changes in both diet and exercise. The primary end point was a HbA1c change over 52 weeks. Results Among the patients, 581 were assigned to the ITG and 578 were in the CTG. The changes in HbA1c from baseline to the final measurement at 52 weeks [mean (standard deviation)] were −0.000 (0.6225)% in ITG and − 0.006 (0.6449)% in CTG, respectively (P = 0.8766). In the per protocol set, including ITG using the IoT system almost daily and CTG, excluding those using the application almost daily, the difference in HbA1c from baseline to 52 weeks were −0.098 (0.579)% and 0.027 (0.571)%, respectively (P = 0.0201). We observed no significant difference in the adverse event profile between the groups. Conclusions The IoT‐based approach did not reduce HbA1c in patients with type 2 diabetes. IoT‐based intervention using data on the daily glycemic control and HbA1c level may be required to improve glycemic control.

Abstract Aims/Introduction This study aimed to identify risk factors that contribute to the progression of slowly‐progressive type 1 diabetes by evaluating the positive predictive value (PPV) of factors associated with the progression to an insulin‐dependent state. Materials and Methods We selected 60 slowly‐progressive type 1 diabetes patients who tested positive for glutamic acid decarboxylase autoantibodies (GADA) at diagnosis from the Japanese Type 1 Diabetes Database Study. GADA levels in these patients were concurrently measured using both radioimmunoassay (RIA) and enzyme‐linked immunosorbent assay (ELISA) techniques. Results Compared with the non‐progressor group (fasting C‐peptide [F‐CPR] levels maintained ≥0.6 ng/mL), the progressor group showed a younger age at diagnosis, lower body mass index (BMI), lower F‐CPR levels and a higher prevalence of insulinoma‐associated antigen‐2 autoantibodies (IA‐2A). The PPV of RIA‐GADA increased from 56.3 to 70.0% in the high titer group (≥10 U/mL), and further increased to 76.9, 84.2, 81.0 and 75.0% when combined with specific thresholds for age at diagnosis

Key Clinical Message In addition to the reentrant map, the wave speed map can be helpful in accurately identifying the CTI gap during radiofrequency application for atrial flutter(AFL). However, in complex cases involving extensive scarring and multiple low‐velocity local areas, this technique may not be useful. Abstract A 73‐year‐old male patient with a history of pulmonary vein isolation and cavotricuspid isthmus ablation underwent a second catheter ablation owing to recurrent atrial flutter (AFL). The AFL was diagnosed as cavotricuspid isthmus‐dependent AFL caused by the reconnection of the previous cavotricuspid isthmus ablation. Wave speed mapping was performed at the same site, and results comprehensively revealed a low‐velocity local area. The AFL was terminated after the first radiofrequency application, and the block line was easily completed. Therefore, this technique could be an adjunctive tool for cavotricuspid isthmus gap identification and minimal radiofrequency application.

Abstract Alterations in the white matter have been implicated in schizophrenia. Myelin basic protein (MBP), a component of the myelin sheath, in the cerebrospinal fluid (CSF) has been suggested as a biomarker for white matter damage in demyelinating diseases. This prompted us to examine the CSF‐MBP levels in patients with schizophrenia. We analyzed the CSF‐MBP levels in 152 patients with schizophrenia and 117 age‐ and sex‐matched controls. A significant positive correlation between age and CSF‐MBP levels was observed both in the patients (p

Abstract Although stereotactic body radiotherapy (SBRT) is a curative treatment option for stage I non‐small cell lung cancer (NSCLC), limited data are available regarding chest wall (CW) toxicities during an extended follow‐up of over 10 years. We report an unusual case of a bone tumor‐like CW mass lesion with pathological rib fractures observed 13 years after SBRT for peripheral lung cancer. Despite the initial suspicion of radiation‐induced sarcoma, a subsequent incisional biopsy revealed no evidence of malignancy, and a definitive diagnosis of osteonecrosis was made. Thus, long‐term observation of over 10 years is required to identify late chronic complications following SBRT.

Abstract Background Recent advancements in advanced non‐small‐cell lung cancer (NSCLC) treatment have significantly improved primary therapy outcomes owing to the emergence of various molecular targeted therapies and immune checkpoint inhibitors (ICIs). However, for Kirsten rat sarcoma viral antigen (KRAS) mutations, molecular targeted drugs, such as sotorasib, are not applicable as first‐line treatments, and the optimal primary treatment remains unclear. Therefore, we aimed to investigate the efficacy of ICI combination therapy as first‐line treatment for KRAS‐mutant NSCLC. Methods We conducted a systematic search for phase 3 randomized controlled trials (RCTs) that presented data on KRAS mutation status in advanced NSCLC. The primary endpoints were progression‐free survival (PFS) and overall survival (OS). A random‐effects network meta‐analysis was conducted to perform direct and indirect comparisons among treatment groups. Results Six RCTs were eligible for inclusion. In the network meta‐analysis for KRAS‐mutant NSCLC, Chemo + bevacizumab (Bev) + ICI was associated with improved PFS (hazard ratio [HR] 0.38, 95% confidence interval [CI] 0.22–0.64), followed by Chemo + ICI + ICI (HR 0.66, 95% CI 0.47–0.93) and Chemo + ICI (HR 0.67, 95% CI 0.49–0.91). The most beneficial effect on OS was observed with Chemo + Bev + ICI (HR 0.50, 95% CI 0.34–0.73), followed by Chemo + ICI + ICI (HR 0.64, 95% CI 0.48–0.87) and Chemo + ICI (HR 0.72, 95% CI 0.56–0.92). Regarding OS in wild‐type KRAS, ICI + ICI (HR 0.73, 95% CI 0.50–1.07) produced the most favorable effects, followed by Chemo + ICI (HR 0.79, 95% CI 0.63–0.99). Conclusion The efficacy of Chemo + Bev + ICI is potentially high for improving PFS and OS in KRAS‐mutant NSCLC. In advanced NSCLC, the presence or absence of KRAS mutations may need to be considered when administering first‐line treatment.

Abstract Transient acantholytic dermatosis (TAD) is a relatively common skin disease that typically affects older individuals, which shows clinical and histologic similarities to autosomal dominant Darier disease. TAD was recently shown to be caused by somatic ATP2A2 damaging variants. In this study, we performed Sanger sequencing and droplet digital PCR (ddPCR) in a Japanese elderly male with TAD to identify ATP2A2 somatic mosaicism occurring during embryogenesis for the first time and mutant allelic fraction (MAF). Sanger sequencing revealed a known heterozygous substitution c.1645C>T, p.Arg549* in ATP2A2 from blood and the affected skin containing the epidermis and dermis, whereas the signals of the mutated allele were weaker, suggesting that discrepancy of signal intensities demonstrates the presence of somatic mosaicism. By ddPCR, the normal and mutant allele were identified in genomic DNAs and the MAFs were 20.1% (affected skin) and 14.7% (blood), respectively. In the present case, somatic mosaicisms observed in ectodermal (epidermis) and mesodermal (dermis and blood) origin DNA can be explained by a mutational event during the early‐stage differentiation of embryonic epiblast in embryogenesis, and mutant embryonic cells somewhat preferentially differentiate to form the epidermis, rather than the dermis and blood. Disrupted intracellular Ca2+ homoeostasis through clinical deterioration together with ATP2A2 somatic mosaicism in this patient might result in transient skin eruptions.

Abstract Purpose Postoperative venous thromboembolism (VTE) risk is pronounced after abdominal cancer surgery. Enoxaparin shows promise in preventing VTE in gastrointestinal, gynecological, and urological cancers, but its application after surgery for hepatobiliary‐pancreatic malignancy has been under‐evaluated due to bleeding concerns. We confirmed the safety of enoxaparin administration in patients undergoing curative hepatobiliary‐pancreatic surgery for malignancies in a prospective, multi‐center, phase I study. Methods The study was conducted from April 2015 to May 2021 across eight specialized centers. Patients (n = 262) were randomized to enoxaparin prophylaxis given postoperatively for 8 days (n = 131) or control (n = 131). The primary endpoint was the efficacy in reducing VTE. Secondary endpoints examined safety. Results The full analysis set included 259 patients (131 control, 129 enoxaparin). The per‐protocol population included 233 patients (117 control, 116 enoxaparin). Most cases were hepatic malignancies (111 control, 111 enoxaparin). The median administration duration of enoxaparin was 7 days, with 92% receiving 4000 units/day. Despite a reduction in the relative risk (RR) of VTE due to postoperative enoxaparin administration, the results were not significant (control: four cases, 3.4% vs. treatment: two cases, 1.7%; RR 0.50, 95% CI 0.09–2.70; p = 0.6834). No significant difference was found in the incidence of bleeding events (control: five cases, 4.3% vs. treatment: five cases, 4.3%, RR 1.00, 95% CI 0.53–1.89; p = 1.0000). Conclusions The perioperative administration of enoxaparin in hepatobiliary‐pancreatic malignancies is feasible and safe. However, further case accumulation and investigation are necessary to assess its potential in reducing the occurrence of VTE.

Abstract Background Predicting the origin of premature ventricular contraction (PVC) from the preoperative electrocardiogram (ECG) is important for catheter ablation therapies. We propose an explainable method that localizes PVC origin based on the semantic segmentation result of a 12‐lead ECG using a deep neural network, considering suitable diagnosis support for clinical application. Methods The deep learning‐based semantic segmentation model was trained using 265 12‐lead ECG recordings from 84 patients with frequent PVCs. The model classified each ECG sampling time into four categories: background (BG), sinus rhythm (SR), PVC originating from the left ventricular outflow tract (PVC‐L), and PVC originating from the right ventricular outflow tract (PVC‐R). Based on the ECG segmentation results, a rule‐based algorithm classified ECG recordings into three categories: PVC‐L, PVC‐R, as well as Neutral, which is a group for the recordings requiring the physician's careful assessment before separating them into PVC‐L and PVC‐R. The proposed method was evaluated with a public dataset which was used in previous research. Results The evaluation of the proposed method achieved neutral rate, accuracy, sensitivity, specificity, F1‐score, and area under the curve of 0.098, 0.932, 0.963, 0.882, 0.945, and 0.852 on a private dataset, and 0.284, 0.916, 0.912, 0.930, 0.943, and 0.848 on a public dataset, respectively. These quantitative results indicated that the proposed method outperformed almost all previous studies, although a significant number of recordings resulted in requiring the physician's assessment. Conclusions The feasibility of explainable localization of premature ventricular contraction was demonstrated using deep learning‐based semantic segmentation of 12‐lead ECG. Clinical trial registration: M26‐148‐8.

Abstract Background Patients with atrial fibrillation (AF) who are not suitable for long‐term anticoagulant therapy undergo percutaneous left atrial appendage closure (LAAC). The safety and feasibility of left atrial catheter ablation (CA) procedures after LAAC remain unclear. This study aimed to clarify the feasibility and safety of CA after LAAC, including in the early phase within 180 days. Methods Characteristics and clinical outcomes of 46 patients with AF who had undergone both CA and LAAC within 2 years (mean age, 72 years; 29 men) were compared between those who had undergone CA‐first (31 patients) and LAAC‐first (15 patients). Results The mean CHA₂DS₂‐VASc and HAS‐BLED scores were 4.8 and 3.3 points, respectively. The LAAC‐first strategy was often used in patients with prior major bleeding and LAA thrombosis or sludge. In the LAAC‐first group, the mean duration between both procedures was 212 days, and all LAAC‐first patients, including seven patients in the early phase, could undergo CA without LAAC device‐related complications; moreover, no cardiovascular adverse events were reported after both procedures (mean periods: 420 days). After CA post‐LAAC, no device‐related adverse events (device‐related thrombosis, new peri‐device leak appearance, peri‐device leak increase, or device dislodgement) were observed, whereas, after LAAC post‐CA, 3 new peri‐device leak appearance events and 1 peri‐device leak increase event were observed, especially patients who underwent LAAC in the early phase post‐CA. Conclusion Based on single‐center experience, left atrial CA in the presence of an LAAC device implanted including the early phase was safe and feasible.

Viral infections in tubular epithelial cells lead to the production of inflammatory cytokines by innate immunity, causing tubulointerstitial nephritis. TLR3 recognizes viral infections and acts via the activation of interferon (IFN)/IFN‐stimulated genes (ISGs). This study investigates the role of ISG56, a representative ISG, in TLR3 signaling in cultured human renal proximal tubular epithelial cells (hRPTECs). To this end, hRPTECs were stimulated by a synthetic TLR3 ligand, polyinosinic‐polycytidylic acid (poly IC), recombinant human interferon‐β [r(h)IFN‐β] or Japanese encephalitis virus (JEV) infection and assayed for inflammatory cytokine mRNA expression by RT‐qPCR, and protein expression via western blotting or ELISA. ISG56 was expressed by poly IC or r(h)IFN‐β and IFN‐β knockdown reduced poly IC‐induced expression of ISG56 and CXCL10. Moreover, ISG56 knockdown reduced poly IC‐ or r(h)IFN‐β‐induced expression of CXCL10 at the same time as increasing JEV growth and reducing CXCL10 expression induced by JEV infection. Overall, TLR3 signaling induced IFN‐β‐dependent expression of ISG56 and CXCL10. We show that ISG56 possibly plays a critical role in antiviral immunity of hRPTECs by positive regulation of IFN‐β‐mediated CXCL10 expression downstream of TLR3.

ABSTRACT Aim/Introduction This historical cohort study sought to research the relationship between eating behaviors and the incidence of type 2 diabetes in a large, long‐term cohort of Japanese subjects. Materials and Methods Panasonic Corporation employees who had no history of diabetes and attended yearly health surveys between 2008 and 2018 were included in this study. The main outcome measure was diabetes onset. Results This study included 128,594 participants and 6,729 participants who developed type 2 diabetes in the study period. Skipping breakfast, fast eating, snacking after dinner, and eating meals before sleeping were linked with the risk of the incidence of type 2 diabetes. In individuals with a BMI

Abstract Aims A considerable proportion of candidates for transcatheter aortic valve implantation (TAVI) have underlying heart failure (HF) with preserved ejection fraction (HFpEF), which can be challenging for diagnosis because significant valvular heart disease should be excluded before diagnosing HFpEF. This study investigated the long‐term prognostic value of the pre‐procedural H2FPEF score in patients with preserved ejection fraction (EF) undergoing TAVI. Methods and results Patients who underwent TAVI between October 2013 and May 2017 were enrolled from the Optimized CathEter vAlvular iNtervention–Transcatheter Aortic Valve Implantation Japanese multicentre registry. After excluding 914 patients, 1674 patients with preserved EF ≥ 50% (median age: 85 years, 72% female) were selected for calculation of the H2FPEF score and were dichotomized into two groups: the low H2FPEF score [0–5 points; n = 1399 (83.6%)] group and the high H2FPEF score [6–9 points; n = 275 (16.4%)] group. Patients with high H2FPEF scores were associated with a higher prevalence of New York Heart Association Functional Class III/IV (59.3% vs. 43.7%, P

Abstract When a mass occurs at the staple line following lung resection, it can be difficult to distinguish between local cancer recurrence and granuloma. We present a case of a staple‐line granuloma with 18F‐fluorodeoxyglucose‐positron emission tomography uptake and elevated serum carbohydrate antigen 19–9 (CA19‐9) in a patient with ovarian cancer lung metastasis. After granuloma resection, serum CA19‐9 levels normalized, and CA19‐9 positive cells were identified in the resected tumor. Therefore, serum CA19‐9 elevation does not rule out a staple‐line granuloma. Whereas granulomas on computed tomography (CT) scans tend to show smooth shadows along the staple line unilaterally, detailed CT evaluation may help diagnostic differentiation. Differentiation based on imaging and tumor markers has limitations. However, core needle biopsy has the risk of misdiagnosis and tumor cell dissemination, therefore surgical resection should be considered when comprehensive findings indicate a potential recurrence.

Abstract Background To elucidate the treatment and surgery outcomes with or without perioperative therapies in Japanese patients with clinical stage III non‐small cell lung cancer (NSCLC) in real‐world settings. Methods We performed subset analyses of the SOLUTION study, a multicenter, noninterventional, observational study of Japanese patients diagnosed with clinical stage III NSCLC, for those who started first‐line treatment (surgery±perioperative therapy) between January 2013 and December 2014 (study registration: UMIN000031385). Follow‐up data were obtained using medical records from diagnosis to March 1, 2018. Results Of 149 eligible patients, 67 underwent surgery alone (median age 71 years) and 82 underwent surgery+perioperative therapy (median age 63 years). Lung resection was performed in 137 patients and the others underwent exploratory thoracotomy or other procedures. Perioperative therapies included adjuvant therapy only (n = 41), neoadjuvant therapy only (n = 24), and neoadjuvant+adjuvant therapy (n = 17). The median overall survival (OS) and 3‐year OS rate were 29.3 months and 44.0%, respectively, in patients who underwent surgery alone, and not reached and 61.1%, respectively, in patients who underwent surgery+perioperative therapy. The 3‐year progression‐free survival (PFS) and disease‐free survival (DFS) rates were 42.4% and 47.1%, respectively, in patients who underwent surgery+perioperative therapy and 28.5% and 28.9%, respectively, in patients who underwent surgery alone. In multivariable Cox regression, perioperative therapy was associated with improved OS (hazard ratio [95% confidence interval] 0.49 [0.29–0.81]), PFS (0.62 [0.39–0.96]), and DFS (0.62 [0.39–0.97]) versus surgery alone. Conclusions Our study suggested that perioperative therapy may be associated with better survival among patients undergoing surgical treatment of clinical stage III NSCLC.

Abstract Atrial fibrillation (AF) is the most common clinically significant cardiac arrhythmia and is an important risk factor for ischemic cerebrovascular events. This study used machine learning techniques to develop and validate a new risk prediction model for new‐onset AF that incorporated the use electrocardiogram to diagnose AF, data from participants with a wide age range, and considered hypertension and measures of atrial stiffness. In Japan, Industrial Safety and Health Law requires employers to provide annual health check‐ups to their employees. This study included 13 410 individuals who underwent health check‐ups on at least four successive years between 2005 and 2015 (new‐onset AF, n = 110; non‐AF, n = 13 300). Data were entered into a risk prediction model using machine learning methods (eXtreme Gradient Boosting and Shapley Additive Explanation values). Data were randomly split into a training set (80%) used for model construction and development, and a test set (20%) used to test performance of the derived model. The area under the receiver operator characteristic curve for the model in the test set was 0.789. The best predictor of new‐onset AF was age, followed by the cardio‐ankle vascular index, estimated glomerular filtration rate, sex, body mass index, uric acid, γ‐glutamyl transpeptidase level, triglycerides, systolic blood pressure at cardio‐ankle vascular index measurement, and alanine aminotransferase level. This new model including arterial stiffness measure, developed with data from a general population using machine learning methods, could be used to identify at‐risk individuals and potentially facilitation the prevention of future AF development.

Introduction While immune checkpoint inhibitors represent the mainstream treatment for metastatic renal cell carcinoma, a standardized approach following immune checkpoint inhibitors remains unclear. We report a case of metastatic renal cell carcinoma treated with nivolumab rechallenge. Case presentation A 60‐year‐old male with metastatic melanoma was referred to the urology division due to right renal cancer. He was undergoing nivolumab treatment for metastatic melanoma. Radical nephrectomy revealed clear cell renal cell carcinoma, pT3a. Two months post‐surgery, multiple metastases were identified. Despite subsequent administration of interferon‐α, axitinib, and temsirolimus, the metastases progressed. Consequently, nivolumab rechallenge and palliative radiotherapy were initiated, resulting in a durable response for 20 months. However, disease progression occurred, and he died of cancer 4 years after nephrectomy. Conclusion This is the first report of nivolumab rechallenge in metastatic renal cell carcinoma. Although the utility remains unclear, this case suggests that some patients may benefit from nivolumab rechallenge.

Abstract Aims/Introduction Gastrointestinal disturbances and insomnia affect the quality of life of patients with diabetes. However, the relationship between gastrointestinal symptoms and insomnia in patients with diabetes has rarely been analyzed. Thus, aim of this study was to investigate the association between gastrointestinal symptoms and insomnia in patients with type 2 diabetes mellitus. Materials and Methods This cross‐sectional study of patients with type 2 diabetes was carried out from January 2014 to April 2022 using the database of the KAMOGAWA‐DM cohort study. Patient data were collected using a self‐administered questionnaire, and the Izumo Scale and the Athens Insomnia Scale were used to assess gastrointestinal symptoms and insomnia, respectively. Multivariate logistic regression analysis was carried out to determine the association between gastrointestinal symptoms and insomnia. Results A total of 175 patients with type 2 diabetes were included in this study. Patients with insomnia had higher Izumo scores than those without insomnia (P

Abstract Background Distal pancreatectomy (DP) with lymph node (LN) dissection is the standard procedure for pancreatic ductal adenocarcinoma of the tail (Pt‐PDAC). However, the optimal surgery including extent of LN dissection is still being debated. The present study investigated the incidence and prognostic impact of LN metastasis on patients suffering from Pt‐PDAC. Patients and method This multicenter, retrospective study involved 163 patients who underwent DP for resectable Pt‐PDAC at 12 institutions between 2013 and 2017. The frequency of LN metastasis and the effect of LN dissection on Pt‐PDAC prognosis were investigated. Results There were high incidences of metastases to the LNs along the splenic artery in the patients with Pt‐PDAC (39%). The rate of metastases in the LNs along the common hepatic, left gastric, and celiac arteries were low, and the therapeutic index for these LNs was zero. In pancreatic tail cancer located more distally, there were no metastases to the LNs along the common hepatic artery. Multivariate analysis revealed that tumor size was the only independent factor related to recurrence‐free survival (HR = 2.01, 95% CI = 1.33–3.05, p = 0.001). The level of pancreas division and LN dissection along the common hepatic artery did not affect the site of tumor recurrence or recurrence‐free survival. Conclusions LN dissection along the hepatic artery for Pt‐PDAC has little significance. Distal pancreatic transection may be acceptable in terms of oncological safety, but further examination of short‐term outcomes and preservation of pancreatic function is required.

Abstract Aims Remote dielectric sensing (ReDS) represents a contemporary non‐invasive technique reliant on electromagnetic energy to quantify pulmonary congestion. Its prognostic significance within the context of heart failure (HF) patients remains elusive. This study aimed to assess the prognostic implications of residual pulmonary congestion, as gauged by the ReDS system, among patients admitted due to congestive HF. Methods and results We enrolled hospitalized HF patients who underwent ReDS assessments upon admission and discharge in a blinded manner, independent of attending physicians. We evaluated the prognostic impact of the ReDS ratio between admission and discharge on the primary outcome, which encompassed all‐cause mortality and HF‐related re‐hospitalizations. A cohort of 133 patients (median age 78 [72, 84] years, 78 male [59%]) was included. Over a median observation period of 363 days post‐index discharge, an escalated ReDS group (ReDS ratio > 100%), determined through statistical calculation, emerged as an independent predictor of the primary outcome, exhibiting an adjusted hazard ratio of 4.37 (95% confidence interval 1.13–16.81, P = 0.032). The cumulative incidence of the primary outcome was notably higher in the increased ReDS group compared with the decreased ReDS group (50.1% vs. 8.5%, P = 0.034). Conclusions Elevated ReDS ratios detected during the index hospitalization could serve as a promising prognostic indicator in HF patients admitted for treatment. The clinical ramifications of ReDS‐guided HF management warrant validation in subsequent studies.

Abstract Background Anemia has negative effects on long‐term outcomes of rectal cancer patients; however, its status as a risk factor for severe complications is disputed. Perioperative risks may differ based on the severity of pre‐surgical anemia; nonetheless, no previous study has investigated these differences. This study identified risks of severe postoperative complications in rectal cancer patients based on severity of their pre‐surgical anemia. Materials and Methods This study enrolled patients who underwent low anterior resection for rectal cancer and were registered in the Japanese National Clinical Database (NCD) between 2017 and 2019. Anemia severity was categorized into three levels: mild, moderate, and severe. A logistic regression model was applied to calculate the risk‐adjusted odds ratio (OR) of severe complications after surgery. Results This study analyzed a cohort of 51 765 rectal cancer patients who underwent low anterior resection. Results showed that severe complications occurred in 10.9% of patients and were significantly more frequent in patients with anemia (13.6%) than those with normal hemoglobin levels (9.2%). Risk‐adjusted ORs of severe complications in the severe, moderate, and mild anemia groups versus the normal group for males were 1.19 (95% confidence interval [CI]: 0.89–1.58), 1.47 (1.34–1.62), and 1.21 (1.12–1.31), respectively. Those for females were 1.39 (0.90–2.15), 1.64 (1.37–1.97), and 1.36 (1.16–1.58), respectively. Conclusions According to this large cohort study, pre‐surgical anemia significantly increases the risk of severe postoperative complications in rectal cancer patients. Even mild anemia presents a significant risk.

Abstract Aims MitraScore is a novel, simple, and manually calculatable risk score developed as a prognostic model for patients undergoing transcatheter edge‐to‐edge repair (TEER) for mitral regurgitation. As its components are considered prognostic in heart failure (HF), we aimed to investigate the usefulness of the MitraScore in HF patients. Methods and results We calculated MitraScore for 1100 elderly patients (>65 years old) hospitalized for HF in the prospective multicentre FRAGILE‐HF study and compared its prognostic ability with other simple risk scores. The primary endpoint was all‐cause deaths, and the secondary endpoints were the composite of all‐cause deaths and HF rehospitalization and cardiovascular deaths. Overall, the mean age of 1100 patients was 80 ± 8 years, and 58% were men. The mean MitraScore was 3.2 ± 1.4, with a median of 3 (interquartile range: 2–4). A total of 326 (29.6%), 571 (51.9%), and 203 (18.5%) patients were classified into low‐, moderate‐, and high‐risk groups based on the MitraScore, respectively. During a follow‐up of 2 years, 226 all‐cause deaths, 478 composite endpoints, and 183 cardiovascular deaths were observed. MitraScore successfully stratified patients for all endpoints in the Kaplan–Meier analysis (P

Background Although endovascular therapy (EVT) is effective for large ischemic region strokes, the impact of hyperglycemia remains unclear. Methods and Results We analyzed data from the RESCUE‐Japan LIMIT (Recovery by Endovascular Salvage for Cerebral Ultra‐Acute Embolism‐Japan Large Ischemic Core) trial, which randomized stroke patients with Alberta Stroke Program Early Computed Tomography Score of 3 to 5 to EVT versus medical management. Outcomes were compared among patients with normoglycemia (

Background The Direct Oral Anticoagulant (DOAC) Score can predict bleeding risk in patients with atrial fibrillation taking DOACs; however, it lacks external validation. Therefore, this study aimed to assess the association between the DOAC Score and bleeding events in patients with atrial fibrillation who underwent transcatheter aortic valve replacement. Methods and Results This retrospective multicenter cohort study included patients with atrial fibrillation who underwent transcatheter aortic valve replacement, as registered in a Japanese multicenter registry. The primary end point was the incidence of bleeding. Patients were categorized based on their DOAC Score: low and moderate‐ (≤7 points), high‐ (8–9 points), and very high‐risk (≥10 points) groups. Among 1230 patients (mean age 84.6±5.1 years; 457 men), 465 (37.8%) received a vitamin K antagonist, and the remaining patients received DOACs. The low and moderate‐, high‐, and very high‐risk groups included 380 (30.1%), 497 (40.4%), and 353 patients (28.7%), respectively. The 3‐year cumulative incidence of all bleeding events was significantly different among the 3 groups (low and moderate risk: 6.6%, high risk: 6.9%, and very high risk: 14.0%; P

Background The impact of high‐risk coronary artery plaques identified using optical coherence tomography on late luminal narrowing and clinical events remains poorly understood. Methods and Results This multicenter prospective study included 176 patients who underwent percutaneous coronary intervention and serial optical coherence tomography at baseline and 1‐year follow‐up to investigate nontarget regions with angiographically intermediate stenosis. At 1 year after percutaneous coronary intervention, the coronary artery lumen area decreased significantly from 6.06 (95% CI, 5.60–6.53) mm2 to 5.88 (95% CI, 5.41–6.35) mm2 (difference, −0.18; 95% CI, −0.22 to −0.14 mm2; P

Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a life‐threatening complication post‐acute pulmonary embolism (PE). The assessment of CTEPH incidence and risk factors post‐acute PE in the era of direct oral anticoagulants remains insufficient. Methods and Results The COMMAND VTE Registry‐2 (contemporary management and outcomes in patients with venous thromboembolism registry‐2) is a multicenter registry that recruited consecutive patients with acute symptomatic venous thromboembolism from 31 centers across Japan. The primary outcome was to demonstrate the detection rate of CTEPH after acute PE in routine clinical practice. Out of the 5197 patients with venous thromboembolism included in the COMMAND VTE Registry‐2, 2787 were diagnosed with acute PE. Following a median follow‐up duration of 747 days, 48 cases of CTEPH were detected, and the cumulative diagnosis of CTEPH in routine clinical practice was 2.3% at 3 years. Independent risk factors for the detection of CTEPH by multivariable Cox regression analysis included women (hazard ratio [HR] 2.09 [95% CI, 1.05–4.14]), longer interval from symptom onset to diagnosis of PE (each 1 day, HR 1.04 [95% CI, 1.01–1.07]), hypoxemia at diagnosis (HR 2.52 [95% CI, 1.26–5.04]), right heart load (HR 9.28 [95% CI, 3.19–27.00]), lower D‐dimer value (each 1 μg/mL, HR 0.96 [95% CI, 0.92–0.99]), and unprovoked PE (HR 2.77 [95% CI, 1.22–6.30]). Conclusions In the direct oral anticoagulant era, the cumulative diagnosis of CTEPH after acute PE was 2.3% at 3 years, and several independent risk factors for CTEPH were identified, which could be useful for screening a high‐risk population after acute PE.

Background The Clinical Frailty Scale (CFS) is a useful frailty marker for predicting clinical outcomes in patients undergoing invasive therapy. However, the clinical impact of CFS after transcatheter edge‐to‐edge repair in patients with mitral regurgitation (MR) remains unclear. This study aimed to elucidate the association between the baseline frail status defined by the CFS and clinical outcomes with or without postprocedural MR ≥2+ (post‐MR ≥2+) after transcatheter edge‐to‐edge repair. Methods and Results Based on a Japanese multicenter registry (OCEAN [Optimized Catheter Valvular Intervention]‐Mitral), data from 2078 patients with MR who underwent transcatheter edge‐to‐edge repair were analyzed. The patients were classified into 5 groups: CFS 1 to 3, 4, 5, 6, and ≥7. The procedural and clinical outcomes and post‐MR ≥2+ were compared among the groups. All‐cause mortality for up to 2 years was explored using Cox proportional hazards regression analysis. Although the rates of acute procedural success and post‐MR ≥2+ were similar, all‐cause mortality at 2 years was significantly increased across the 5 CFS categories (15.5%, 23.8%, 27.7%, 34.6%, and 48.8%, respectively, P

Background We aimed to quantify the incidence of atrial fibrillation (AF) in patients with cryptogenic stroke globally, as well as separately in patients in and outside of Japan, using an implantable loop recorder from a prospective, observational, Reveal LINQ Registry. Methods and Results Patients developing cryptogenic stroke and monitored by implantable loop recorder for searching AF were studied. The primary end point was incidence of AF within 36 months after insertion. Secondary end points were recurrent ischemic stroke/transient ischemic attack and AF‐related treatment strategies. A total of 271 patients (61.6±14.3 years, 170 men, 60 from Japan) were enrolled from 12 countries. AF was detected in 28.2% at 36 months. The median time from enrollment to AF detection was 7.9 months. During the first 12 months, the AF detection rate slope was relatively steeper in the Japanese subgroup versus non‐Japanese patients. However, by 3 years, the cumulative incidence of AF detection did not differ between groups. Age was the only variable associated with AF detection (hazard ratio, 1.05 [95% CI, 1.02–1.07] per year), trending higher in older age groups. Of the 271 patients, 11 (4.1%) developed recurrent ischemic stroke/transient ischemic attack; AF was detected by implantable loop recorder in only 1 of these patients. Patients with detected AF were more commonly taking oral anticoagulation than those without AF at the last follow‐up (64.7% versus 25.3%, P

Background Flow diversion has emerged as a promising treatment strategy for intracranial aneurysms, yet the influence of antiplatelet therapy on treatment outcomes remains uncertain. Regional and institutional variability in antiplatelet regimens further complicates treatment standardization. This survey aimed to investigate common practices of antiplatelet medication usage in flow diversion for intracranial aneurysms worldwide. Methods An anonymous online survey explored antiplatelet therapy regimens in flow diverter implantations, including agent selection, dosing, and duration. The survey was distributed through international neurointerventional societies and mailing lists. Results Participants included 442 from 53 countries, revealing that most practitioners agree on using dual antiplatelet therapy, with 67% combining low‐dose aspirin with clopidogrel. However, alternative P2Y12 inhibitors are increasingly being used with the main reasons for preferring ticagrelor (21%) over prasugrel (10%) being its availability and bleeding risk, whereas the main reason for using prasugrel over ticagrelor is patient compliance. Resistance testing for antiplatelet agents was conducted by 62% of survey respondents, with the VerifyNow system being the most common method. Strategies to manage resistance included dose escalation (17%) and switching (83%) to alternative agents. Interest in participating in future trials investigating antiplatelet therapy duration and dual antiplatelet therapy versus single antiplatelet therapy was high (77% and 58%, respectively). Conclusion Antiplatelet treatment strategies following flow diversion procedures vary globally, with a growing interest in alternative agents and a willingness to participate in future trials. Standardization efforts and further investigation are warranted for optimizing neurointerventional outcomes.

ABSTRACT Background Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer. Recent studies indicated that cancer‐associated adipocytes (CAAs) play crucial roles in tumor progression; however, the precise mechanism remains unknown. Here, we analyzed specific exosomal microRNAs (miRNA) signatures derived from pancreatic CAAs to investigate their role in cancer progression. Methods CAAs were generated by co‐culturing human adipocytes with human pancreatic cancer cells, and exosomes were isolated from the CAA‐conditioned medium (CAA‐CM). Small RNA‐seq analysis was used to identify differentially expressed miRNAs in these exosomes. The effects of miRNAs on cell proliferation, migration/invasion, and drug sensitivity were examined. Luciferase reporter assays, real‐time polymerase chain reaction, and western blotting were performed to investigate the molecular mechanisms of the miRNAs. The clinical relevance of the miRNAs was investigated using publicly available data and our cohort of patients with PDAC. Results miR‐199a‐3p expression was significantly increased in CAA‐CM‐derived exosomes. CAA‐derived exosomes transferred miR‐199a‐3p to pancreatic cancer cells. Transfection with miR‐199a‐3p increased the proliferation, invasion, migration, and drug resistance of pancreatic cancer cells by downregulating SOCS7, increasing STAT3 phosphorylation, and upregulating SAA1 expression. High tissue miR‐199a‐3p expression is correlated with poor prognosis in patients with PDAC. Liquid biopsies revealed that exosomal miR‐199a‐3p could accurately differentiate patients with PDAC from healthy controls. Multivariate survival analysis indicated that miR‐199a is an independent prognostic factor for PDAC. Conclusion miR‐199a‐3p in CAA‐derived exosomes contributes to the malignant transformation of pancreatic cancer via the SOCS7/STAT3/SAA1 pathway, suggesting its potential as a biomarker and therapeutic target for PDAC.