e16095 Background: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced esophageal squamous cell carcinoma (ESCC). In the era of immunotherapy, it is worth exploring whether the combination of CCRT and immunotherapy can improve efficacy. This study aimed to evaluate the efficacy and safety of preoperative anti-PD-L1 Immunotherapy combined with CCRT in ESCC. Methods: In this phase II trial, patients (pts) with resectable, locally advanced ESCC received neoadjuvant durvalumab (1500mg, Q4W) combined with CCRT (41.4Gy/23f with weekly paclitaxel/carboplatin), followed by surgery. Co-primary endpoints were the objective response rate (ORR, irRECIST) and pathologic complete response (pCR, CAP). Secondary endpoints included safety, surgical outcomes, disease-free survival (DFS), and overall survival (OS) (NCT04568200). Results: As of January 26, 2026, 34 pts were enrolled. Among the 27 pts who completed neoadjuvant therapy and were evaluable for efficacy, the ORR was 88.9% (comprising 1 complete, 22 partial responses, 3 stable disease and 1 progression disease), and the disease control rate (DCR) was 96.3%. The neoadjuvant therapy was completed in a median of 32 days. The regimen was manageable, with 24 pts (90.3%) completing the full radiotherapy course, and all pts completing two cycles of immunotherapy. The median interval from the completion of radiotherapy to surgery was 51.5 days. Of the 27 evaluable patients, 23 were deemed eligible for surgery. Ultimately, 22 pts underwent McKeown minimally invasive esophagectomy, all of whom achieved R0 resection. Pathologic assessment of these surgical specimens showed a primary tumor pCR rate of 50% (11/22) and a pCR rate in both primary tumor and lymph nodes (ypT0N0) of 36.4% (8/22). The major pathologic response (MPR) rate was 72.7% (16/22). The median number of lymph nodes harvested was 44 (range, 25-63). At a median follow-up of 10.7 months, the estimated 1-year DFS rate was 86.3% in the surgical cohort (n=22), and the 1-year OS rate was 97.1% in the intention-to-treat population (n=34). Common AEs included leukopenia/neutropenia (n=14), radiation esophagitis (n=7), pneumonia (n=2), intestinal obstruction(n=1), myocardial infarction due to coronary heart disease (n=1). Two patients contracted COVID-19. No new safety signals were identified. Conclusions: Anti-PD-L1 Immunotherapy combined with CCRT in locally advanced ESCC might be a useful treatment option with highly promising efficacy and manageable safety. Clinical trial information: NCT04568200 .

PurposeTo comprehensively and systematically explore adverse drug reactions (ADRs) associated with ophthalmic atropine, providing evidence-based safety references for clinical medication practices.MethodsSignal detection for ophthalmic atropine-associated ADRs was conducted using the Information Component (IC) and Reporting Odds Ratio (ROR) methods, analyzing data from the inception of the FDA Adverse Event Reporting System (FAERS) database through the second quarter of 2025.ResultsThe FAERS database contained 425 reports of ophthalmic atropine-associated ADRs, with 83 positive signals detected. These signals primarily involved eye disorders, nervous system disorders, injury, poisoning and procedural complications, and infections and infestations. Endophthalmitis (n = 74, IC025 = 6.62, ROR025 = 101.90) was the most frequent and strongest ADR signal detected. Other high-intensity ADR signals were choroiditis (IC025 = 6.05, ROR025 = 69.26), intraocular pressure increased (IC025 = 5.77, ROR025 = 56.93), visual acuity reduced (IC025 = 5.46, ROR025 = 45.74), mydriasis (IC025 = 5.36, ROR025 = 43.34), and uveitis (IC025 = 5.36, ROR025 = 42.93). Additionally, eye pain (n = 64, IC025 = 4.99, ROR025 = 32.90) represented another frequently reported ADR after endophthalmitis. Of the preferred terms, 81.93% were assigned a grade of weak clinical priority, with the remainder (18.07%) falling into the moderate category.ConclusionOphthalmic atropine demonstrates potential ADR burdens in ocular systems, necessitating heightened clinical vigilance and prompt risk mitigation strategies to ensure medication safety. It should be noted that these findings represent safety signals from a spontaneous reporting database, not incidence estimates or proof of causality.

Concerns regarding neuropsychiatric adverse events (NPAEs), including depression and suicidality, have emerged with the expanding use of GLP-1-based therapies across metabolic and weight-management indications. This study aimed to characterize neuropsychiatric adverse-event reporting patterns for GLP-1-based therapies in VigiBase using disproportionality analysis. Individual case safety reports entered into the WHO global pharmacovigilance database (VigiBase) from inception through 31 January 2025 were examined. Disproportionality analysis using the information components and the reporting odds ratio was conducted to identify putative safety signals. The full VigiBase reporting background during the study period was used as the comparator. We described the drug-event pairs, mapped signal overlap across agents, evaluated the relationship between reporting frequency and signal magnitude, and conducted stratified analyses by sex and age. Among 899 280 GLP-1RAs-related reports, 19 811 (2.2

AIMS:To investigate the longitudinal associations of MAFLD with CKD risk. METHODS:A total of 10,817 participants derived from the Dongfeng-Tongji (DFTJ) cohort were classified as non-fatty liver disease (non-FLD), non-alcoholic fatty liver disease (NAFLD) without metabolic dysfunction (MD), and MAFLD group. The 8,843 participants had qualitatively controlled genotyping data. An estimated glomerular filtration rate (eGFR) of less than 60 ml/min/1.73 m2 was defined as CKD. RESULTS:Among 10,817 individuals, 1,845 participants developed CKD during ten-year of follow-up. The incidence of CKD was 15.8 %, 10.0 %, and 19.9 % among non-FLD, NAFLD without MD, and MAFLD groups, respectively. Compared with non-FLD participants, the risk of CKD significantly increased in MAFLD group, with the multivariable-adjusted odds ratio (OR) and 95 % confidence interval (CI) of 1.25 (1.11-1.40). Moreover, as the number of MAFLD co-existing metabolic dysfunction components increased, the risk of CKD significantly increased (P-trend < 0.001). MAFLD-related genetic risk score (GRS) was positively associated with elevated blood pressure and elevated triglycerides levels (P < 0.05), which mediated 17.8 % and 14.7 % of the association between MAFLD-related GRS and CKD risk, respectively. CONCLUSIONS:CKD risk was associated with MAFLD presence, and gradually increased with the number of MAFLD metabolic components increased. Metabolic diseases might mediate the association between MAFLD-related GRS and CKD risk.

IntroductionAccelerated biological ageing is associated with age-related diseases, but sex differences in its association with cardiovascular disease (CVD) and premature mortality remain largely unknown. We aimed to assess the associations between biological age (BA) acceleration and CVD, premature mortality, and examine potential sex differences.MethodsThis population-based prospective cohort study included participants aged 39 to 71 years from UK Biobank study, recruited between 2006 and 2010, and followed up until Dec 20, 2022. BA, derived from clinical biomarkers, was calculated using the Klemera-Doubal method (KDM-BA) and PhenoAge algorithms. BA acceleration was defined as the residual from regressing BA based on chronological age. Incident CVD and premature mortality (defined as death before age 70) were identified using ICD-9 and ICD-10 codes. Multivariable-adjusted Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) across BA acceleration quartiles.ResultsAmong 122,133 participants who were free of CVD at baseline (mean [SD] age, 56.0 [8.1] years; 65,442 [53.6%] women), 24,281 incident CVD cases and 3,614 premature deaths were reported. Restricted cubic splines showed progressively increasing risks of incident CVD and premature mortality associated with higher BA acceleration. Compared with the lowest quartile of KDM-BA acceleration, the largest adjusted HRs for incident CVD and premature mortality were 1.32 (95% CI 1.27–1.37) and 1.10 (95% CI 1.05–1.21) for quartile 4, respectively. For PhenoAge acceleration, the corresponding HRs were 1.23 (95% CI 1.19–1.28) and 1.21 (95% CI 1.10–1.33), respectively. These associations were more pronounced among male participants (P-interaction<0.05).DiscussionIn this cohort study, higher BA acceleration was associated with increased risks of incident CVD and premature mortality, with more pronounced association observed in males. These findings suggest the need to exploring BA acceleration as a modifiable risk factor to optimize risk assessment, and to implement sex-specific strategies to improve health outcome.

ObjectiveTo investigate the association between dynamic trajectories of intrinsic capacity (IC) and the risk of incident stroke among Chinese adults aged 45 years and older, and to provide a novel perspective for early warning of stroke.MethodsA total of 8 321 participants with IC repeat measurement data from the 2011‒2016 waves of the China Health and Retirement Longitudinal Study (CHARLS) were included. IC was constructed by five dimension indicators: cognition, movement, vitality, sensory, and psychological. A group-based trajectory model was adopted to identify the change trajectory of IC. The primary outcome was the stroke events that occurred from 2017 to 2020. The Cox proportional hazards regression model was used to test the association between IC trajectory and stroke risk.ResultsThree IC trajectories were identified, labeled as the low-stable, medium-stable, and high-stable IC trajectory groups, accounting for 41.70%, 41.63%, and 16.67% of the research population, respectively. Compared with participants in the low-stable IC trajectory group, those in the medium-stable and high-stable groups had a reduced risk of stroke, with multivariable-adjusted hazard ratios of 0.823 (95%CI: 0.689‒0.984) and 0.632 (95%CI: 0.471‒0.848), respectively.ConclusionThe longitudinal trajectories of IC are significantly negatively correlated with the incidence of stroke. IC may serve as a reliable indicator for assessing stroke risk.

The complexity of diagnostic and therapeutic decision-making in esophageal cancer underscores the need for effective teaching strategies to enhance clinical reasoning skills. This study evaluated the association of a problem-based learning (PBL) approach with clinical reasoning ability, theoretical knowledge acquisition, and learning perceptions among medical interns. In this retrospective study, 132 medical interns completing thoracic surgery rotations were included. A control group (n = 64) taught via conventional lectures was compared to an observation group (n = 68) instructed using structured PBL modules. Baseline comparability was confirmed. Outcomes included standardized assessments of clinical reasoning performance, diagnostic accuracy, differential diagnosis formulation, and case presentation quality. Theoretical knowledge was tested via written examinations, and self-evaluation questionnaires assessed perceived learning gains. Data were analyzed using Welch Student t test, Mann-Whitney U test, and Chi-square tests, with P < .05 considered significant. Compared to the control group, the PBL group demonstrated a higher overall clinical reasoning score (87.4 ± 6.3 vs 79.1 ± 7.2; t = 7.059, P < .001) and greater diagnostic accuracy (92.6% vs 68.8%; χ2 = 12.264, P = .001). The PBL approach was also associated with superior theoretical knowledge scores (85.7 ± 5.9 vs 81.0 ± 6.6; t = 4.319, P < .001) and higher sub-domain scores in pathophysiology, diagnostic interpretation, and treatment principles (all P < .01). Student self-assessments indicated higher satisfaction, stronger self-reported critical thinking, and greater perceived integrative ability in the PBL cohort (all P < .001). The structured PBL model was significantly associated with improved clinical reasoning, theoretical knowledge, and self-perceived competence in esophageal cancer education. These findings suggest the potential value of integrating PBL into competency-based medical training for complex oncological diseases.

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are key therapies for type 2 diabetes and obesity, regulating blood glucose by mimicking endogenous GLP-1. Despite efficacy, GLP-1 RAs are associated with adverse reactions across multiple organ systems. To address the gap in class-wide comparative safety analyses beyond previous studies limited to single drugs or organ systems, this study systematically evaluated adverse events for all approved GLP-1 RAs to identify hidden risks and support clinical decision-making. We conducted a disproportionality analysis using the World Health Organization pharmacovigilance database (VigiBase) data up to January 2025. Reporting odds ratio (ROR) and information component (IC) were calculated for seven GLP-1 RAs. Signals were considered significant when ROR025 > 1 and IC025 > 0. Subgroup analyses were stratified by gender and age. We aimed to synthesize and analyze existing randomized controlled trials (RCT) to validate VigiBase mining results. Among 348,649 reports, gastrointestinal disorders were the most frequent System Organ Class. Notable signals included tirzepatide with “abdominal pain” (ROR025 = 53.54), liraglutide with “drug ineffective” (ROR025 = 31.14) and “pancreatitis” (ROR025 = 4.24), exenatide with “injection site pain” (ROR025 = 70.14), and albiglutide with “device use error” (ROR025 = 1424.33). Male patients and younger adults (18–44 years) generally showed higher positive reporting rates. This study provides a comprehensive safety comparison across all seven approved GLP-1 RAs, confirming known risks and revealing drug-specific signals—such as injection-related issues and paradoxical hyperglycemia. These findings aid personalized treatment strategies and post-marketing surveillance.

BACKGROUND:Premature atrial contractions (PACs) are independently associated with atrial fibrillation, stroke, and heart failure, yet no pharmacological therapy is approved for PAC suppression. Experimental studies have identified a functional cardiac glutamatergic system in which N-methyl-D-aspartate receptors regulate atrial electrophysiology. Preclinical studies show that pharmacological antagonism of N-methyl-D-aspartate receptors with memantine suppresses atrial arrhythmias. METHODS:We conducted an investigator-initiated, phase 2, multicenter, randomized, double-blind, placebo-controlled trial. Symptomatic adults with frequent PACs (≥1000/24 h) were randomly assigned to receive memantine or placebo for 6 weeks. The primary end point was the percentage change in mean 24-hour PAC count from baseline to the end of treatment. The primary analysis was performed in the intention-to-treat population. Prespecified secondary end points included the responder rate (≥50% PAC reduction), percentage change in nonsustained atrial tachycardia burden, and cumulative incidence of new-onset atrial fibrillation. RESULTS:Among 241 patients included in the efficacy analysis, memantine resulted in a greater reduction in PAC count than placebo (between-group difference, 47.1 percentage points; P=0.0045). The responder rate was higher with memantine than with placebo (52.4% versus 23.1%; P<0.0001). Memantine also reduced nonsustained atrial tachycardia burden (between-group difference, 30.98 percentage points; P=0.0043) and was associated with a lower cumulative incidence of new-onset atrial fibrillation (4.8% versus 23.9%; P<0.0001). No clinically meaningful differences were observed in electrocardiographic intervals or left ventricular function, and no drug-related serious adverse events occurred. CONCLUSIONS:In patients with frequent symptomatic PACs, memantine reduced atrial ectopy and atrial tachyarrhythmia burden and demonstrated a favorable safety profile. These findings provide proof of concept for a novel, non-ion channel-based therapeutic strategy targeting the cardiac glutamatergic system. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: NCT06501638.

Supplementary Figure 1. Chemical structure of NMDl14

BackgroundCrohn’s disease (CD) is a chronic inflammatory bowel condition with increasing global incidence. Diet is a key modulator of chronic inflammation, often assessed by the Dietary Inflammatory Index (DII). However, prospective evidence linking the DII to CD risk remains limited in large populations. This study used the UK Biobank (UKB) to address this gap.MethodsCox regression models were used to examine the association between the energy adjusted dietary inflammation index (E-DII) quartiles and CD with sequential adjustment for confounding variables. Restricted cubic spline regression (RCS) was additionally adopted to determine the association of the continuous E-DII and CD risk. Furthermore, sensitivity and subgroup analyses were conducted to explore the consistency of the results.ResultsAmong 207,582 participants included in the analysis, 455 incident CD cases were documented over a mean follow-up period of 12.65 years. A positive association was observed between higher E-DII scores, indicating a more pro-inflammatory diet, and an increased risk of CD. In a fully adjusted multivariable model, participants in the highest quartile of E-DII had a significantly elevated risk of CD [HR:1.45, 95% CI (1.11–1.90); p < 0.01] compared to those in the lowest quartile. This association remained consistent across several sensitivity analyses.ConclusionIn this large prospective cohort, a pro-inflammatory dietary pattern, as reflected by higher E-DII scores, was associated with a significantly increased risk of developing CD. From a public health perspective, this finding highlights the potential importance of dietary inflammation in CD prevention, warranting further investigation into targeted interventions.

BackgroundChimeric antigen receptor (CAR) T-cell therapy is increasingly used for hematologic malignancies, yet the spectrum and clinical significance of its endocrine adverse events (AEs) remain poorly characterized.ObjectiveTo identify and clinically contextualize signals of endocrine AEs associated with CAR T-cell therapy, with a focus on their overlap with cytokine release syndrome (CRS).MethodsWe performed a retrospective disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) database (2017 to Q2 2025). Reporting odds ratio (ROR) and information component (IC) were calculated for endocrine AEs associated with six CAR T-cell products. To validate and elaborate these pharmacovigilance signals, a structured literature review was conducted to identify published clinical evidence.ResultsThe FAERS analysis identified 269 endocrine AE reports, yielding 14 significant disproportionality signals. Hyperglycemia was the most frequently reported event, while estrogen deficiency showed the strongest signal strength (ROR₀₂₅ = 14.93). Signals for adrenal insufficiency and hypothalamo-pituitary disorders were primarily associated with axicabtagene. Critically, mortality was frequently reported among cases with positive endocrine signals, particularly when the endocrine AE co-occurred with CRS. The literature review provided direct clinical validation: a retrospective study confirmed a 39% incidence of CRS-associated hyperglycemia, and independent case reports documented the first instances of CAR T-cell therapy-induced Hashimoto’s thyroiditis and central diabetes insipidus. These clinical cases corroborated the FAERS signals and suggested immune-inflammatory mechanisms, often independent of corticosteroid use.ConclusionThis integrated analysis reveals a distinct spectrum of CAR T-cell-related endocrine toxicities, encompassing glucose and calcium dysregulation, pituitary axis disorders, and autoimmune phenomena. The frequent and potentially fatal overlap with CRS underscores the need for enhanced clinical vigilance. Proactive monitoring of endocrine function, especially in patients experiencing CRS, is warranted to mitigate these underrecognized complications.

Medical institutions, with their clinical practice foundation and abundant human use experience data, have become important carriers for the inheritance and innovation of traditional Chinese medicine(TCM) and the "cradles" of the preparation of new TCM. To effectively promote the transformation of new TCM originating from the TCM clinical practice in medical institutions and establish an effective evaluation index system for the transformation of new TCM conforming to the characteristics of TCM, consensus experts adopted the literature research, questionnaire survey, Delphi method, etc. By focusing on the policy and technical evaluation of new TCM originating from the TCM clinical practice in medical institutions, a comprehensive evaluation from the dimensions of drug safety, efficacy, feasibility, and characteristic advantages was conducted, thus forming a comprehensive evaluation system with four primary indicators and 37 secondary indicators. The expert consensus reached aims to encourage medical institutions at all levels to continuously improve the high-quality research and development and transformation of new TCM originating from the TCM clinical practice in medical institutions and targeted at clinical needs, so as to provide a decision-making basis for the preparation, selection, cultivation, and transformation of new TCM for medical institutions, improve the development efficiency of new TCM, and precisely respond to the public medication needs.

BackgroundMaternal obesity is associated with adverse pregnancy outcomes. It negatively affects IVF/ICSI outcomes and offspring health. However, it is unclear whether waist-hip ratio (WHR) has an impact on outcomes of in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles.MethodsA retrospective cohort study screened 943 patients who underwent IVF/ICSI treatment between February and June 2020 in Shanghai, China, and 828 patients were finally included in the analyses. The body weight, height, waist circumference and hip circumference were measured before ovarian stimulation, and their IVF/ICSI outcomes were followed up. The cut-off point of WHR was determined by the area under the receiver operating characteristic (ROC) curve. Live birth rate from the first embryo transfer cycle was the primary outcome. The secondary outcomes included cumulative live birth, miscarriage rate and birthweight.ResultsWomen with relatively high WHR (≥0.783) showed lower live birth rate (adjusted odds ratio (aOR): 0.657, 95%CI: 0.466-0.926), lower cumulative live birth rate (aOR: 0.580, 95%CI: 0.413-0.814), and higher miscarriage rate (aOR=2.865, 95%CI: 1.300-6.316) as compared with those with low WHR (<0.783), independently of BMI. Joint WHR and BMI analyses showed that, compared with the reference group (those with low WHR and normal weight), those with high WHR and normal BMI had lower live birth rate (aOR=0.653, 95%CI: 0.447-0.954) and cumulative live birth rate (aOR=0.600, 95%CI: 0.413-0.872), and higher miscarriage rate (aOR=2.865, 95%CI: 1.229-6.676), Whereas the patients with both high WHR and high BMI only showed a significant lower cumulative live birth rate (aOR=0.612, 95%CI: 0.404-0.926). Moreover, there was no significant association between BMI and pregnancy outcomes, or between maternal WHR and birth weights.ConclusionsOur results demonstrated that higher WHR was associated with lower fecundability in women undergoing IVF/ICSI cycles, independently of BMI. Interestingly, the adverse effects of central obesity were more evident in patients with lower BMI. Thus WHR appears to be a better predictor of female fertility treatment outcomes as compared with BMI.

Purpose: Previous studies have shown a conflicting association between body mass index and myopia. This study aimed to analyze the possible association between Body Mass Index (BMI) and myopia in the observational design and genetic evidence.Methods: In the observational investigation, 5,710 participants (12-25 years) from the 2001-2006 National Health and Nutrition Examination Survey (NHANES) were included. Weighted logistic regression models, restricted cubic spline (RCS) and stratified analysis were conducted in the NHANES. A two-sample Mendelian Randomization (MR) study using Genome-Wide Association Studies (GWAS) summary statistics and GWAS catalog was performed. The inverse-variance weighted (IVW) method was used as the main analysis method, and the sensitivity analysis was performed to detect pleiotropy and heterogeneity bias.Results: In the fully adjusted model, individuals with obesity had a higher risk of myopia [OR = 1.253, 95% CI= (1.049, 1.496), p = 0.014] and mild and moderate myopia [OR = 1.305, 95% CI= (1.094, 1.558), p = 0.004]. BMI was correlated with refractive spherical equivalent and showed a linear relationship (P for nonlinearity = 0.468, p = 0.002,β=-0.016). In males, obesity had an association with myopia, while there was no statistical significance in females. In the subgroup with an education level of < 9th Grade, obesity and myopia exhibited consistent results. Two-sample MR showed that obesity had no statistically significant with myopia and refractive error.Conclusions: This study suggests that the associations between BMI and the risk of myopia differ based on gender and education levels in an observational study, while there are no associations in genetic evidence.

INTRODUCTION:This study aimed to investigate the trajectory of cognitive decline and explore the association between education levels and the trajectory of cognitive decline among Chinese middle-aged and older adults. METHODS:Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS) among Chinese middle-aged and older adults with five waves of follow-up, 2011-2020. Education levels were self-reported by the participants at baseline. To explore the trajectories of cognitive decline, a group-based trajectory modelling (GBTM) approach was employed. Multivariable logistic regression models were conducted to measure the association between education levels and the trajectories of cognitive decline. Subgroup and sensitivity analyses were also conducted to further explore and validate the association. RESULTS:A total of 6384 Chinese adults were enrolled in the study, with a median age of 56 (P25, P75: 49, 62); 2953 (46.3%) were females. A total of 1402 (22.0%) participants had no formal education at baseline. Three trajectories of cognitive decline were considered in the best GBTM model, including a stable group (37.92%), a mild decline group (42.28%), and a rapid decline group (19.80%). Education levels were associated with cognitive decline trajectories in multivariable logistic regression models (p < 0.05). The subgroup and sensitivity analyses demonstrated comparable results as well. CONCLUSIONS:Three trajectories of cognitive decline (stable, mild and rapid decline) were identified using the GBTM approach. A higher level of education could reduce the risk of cognitive decline among Chinese middle-aged and older adults. Our findings suggest that improving access to education holds significant potential for reducing public health burdens associated with cognitive decline.

INTRODUCTION:Body mass index (BMI) has been implicated in various cardiovascular conditions, but its association with peripheral artery disease (PAD) in both real-world and genetic studies have been contentious and debated. METHODS:This study enrolled 6707 individuals from the National Health and Nutrition Examination Survey database to investigate the association between BMI and the risk of PAD. The weighted logistic regression, restricted cubic spline, and subgroup analysis were performed using real-world data. Mendelian randomization study was conducted using genetic data from the Genome-Wide Association Study. The inverse variance weighted method was used as the primary analysis approach, and a sensitivity analysis was conducted to identify pleiotropy and heterogeneity bias. RESULTS:Individuals with PAD had higher mean BMI values compared to those without PAD (28.82 ± 5.87 and 28.31 ± 5.42, P = 0.007). For the categorical variable of BMI, individuals in obesity class 2 (odds ratio [OR] = 1.532, 95% CI = 1.082-2.169; P = 0.013) and obesity class 3 (OR = 2.479, 95% CI = 1.515-4.056; P < 0.001) had a higher risk of PAD analyzed by weighted logistic regression. Subgroup analysis revealed that the association between BMI and PAD persisted. Given that a higher BMI is associated with PAD, we selected obesity for Mendelian randomization analysis and observed that obesity had a relationship with PAD (inverse variance weight: OR = 1.194, 95% CI = 1.099-1.296; P < 0.001). The reliable findings were validated by sensitive analysis (all P > 0.05). CONCLUSIONS:BMI is a robust risk factor for PAD. A higher BMI (especially ≥35 kg/m2) is associated with an increased risk of developing PAD. Meanwhile, there is a causal relationship between obesity and PAD. Interventions are necessary for targeted obesity prevention and management strategies for PAD.

BACKGROUND:Cardiovascular disease (CVD) risk increases in patients with metabolic-associated fatty liver disease (MAFLD). While sleep duration is linked to CVD risk, it is unclear whether it differs between individuals with and without MAFLD. METHODS:Data from the National Health and Nutrition Examination Survey (2007-2020; n  = 10 386) were analyzed using multivariable logistic regression to examine the relationship between sleep duration and CVD. Subgroup analyses and a restricted cubic spline model assessed interactions and potential nonlinear associations, while Mendelian randomization (MR) was used to infer causality. RESULTS:Long sleep duration (≥9 h) was associated with an increased CVD risk in MAFLD patients [ P  = 0.005, odds ratio (OR) = 1.92, 95% confidence intervals (CI): 1.22-3.02], while short sleep duration (≤6 h) was linked to a higher CVD risk in non-MAFLD individuals ( P  = 0.030, OR = 1.63, 95% CI: 1.05-2.52). Subgroup analysis revealed that marital status modified this association in MAFLD patients. A U -shaped relationship was observed, with the lowest CVD risk occurring at 6.7 h of sleep for MAFLD patients and 7.9 h for non-MAFLD individuals. MR suggested a causal link ( P  = 0.03, OR = 1.42, 95% CI: 1.02-1.97), with the results remaining robust after adjusting for potential confounders. CONCLUSION:Long sleep duration increases CVD risk in MAFLD patients, with a U -shaped relationship indicating the lowest risk at 6.7 h of sleep in MAFLD and 7.9 h in non-MAFLD individuals. MR analysis suggests a causal link between sleep duration and CVD.

To examine and quantify the association between an inflammatory diet index and gastroesophageal reflux disease (GERD) utilizing extensive data from a large cohort. This study included eligible UK Biobank participants recruited between 2006 and 2010 who had no prior history of GERD and no missing data for key covariates. The primary outcome was incident GERD, identified using the “first occurrence” dataset. 27 eligible food/nutrient parameters derived from the 24-h recall questionnaires in the UK Biobank were included to calculate the energy-adjusted dietary inflammation index (E-DII) score. The E-DII score was employed as a continuous variable in restricted cubic spline regression (RCS) analysis. To facilitate analysis, participants were then categorized into four groups based on quartile values in the subsequent Cox regression analysis adjusting varying degrees of confounding factors. After exclusion, 154,590 participants were included in the primary analysis. Over a mean 12.36-year follow-up, a total of 12, 041(7.79

Objectives. - It remains unclear whether the combined use of the triglyceride glucose index (TyG) and body roundness index (BRI), specifically the triglyceride glucose-body roundness index (TyG-BRI), is associated with the incidence of cardiovascular diseases (CVD). This study aimed to investigate the joint association of the TyG and BRI with CVD among middle-aged and elderly adults with abnormal glucose metabolism. Material and methods. - This study obtained four national waves data from China Health and Retirement Longitudinal Study. Patients age >= 45 years with abnormal glucose metabolism were included. The primary outcome was incident CVD. Multivariable-adjusted Cox proportional hazards regression models were employed to assess the joint association of the TyG, BRI and the TyG-BRI with outcomes. Results. - A total of 4805 Chinese adults with abnormal glucose metabolism were enrolled in this study. In the follow-up, 899 participants (18.7%) experienced CVD events. Compared to the first quartile of the index, the fourth quartile ofTyG-BRI was associated with increased risk for CVD by 53.8% (HR, 1.538 [95% CI, 1.249-1.893]). Mediation effects analyses revealed that high TyG index significantly mediated 4.545% (P = 0.016) of the association between a high BRI and CVD incidence, while BRI simultaneously mediated 14.583% (P < 0.001) of the association between high TyG index and CVD. Conclusions. - TyG, BRI, and the combined TyG-BRI index are independently associated with increased risks of CVD among middle-aged and older adults with abnormal glucose metabolism in China. These indicators are easy to obtain and can be implemented in resource-limited primary hospitals to assist clinical practitioners in early screening and assessment of cardiovascular disease risk in patients with abnormal glucose metabolism. (c) 2025 Societe francophone nutrition clinique et metabolisme (SFNCM). Published by Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.