Background: Menopausal status can increase the risk of cardiocerebrovascular diseases (CCVDs) in women with type 2 diabetes mellitus (T2DM). Regular exercise is well-known to reduce this risk. This study explored the impact of exercise on CCVD and mortality in women with T2DM according to their menopausal status. Methods: A total of 32,477 premenopausal and 53,690 postmenopausal Korean women with T2DM aged 40 to 60 years from a national health examination cohort (2009 to 2018) were included. We evaluated risks for stroke, myocardial infarction (MI), and mortality based on exercise intensity. Cox proportional hazard regression analyses were performed to obtain the adjusted hazard ratio (aHR) and 95% confidence interval. Results: Exercise reduced stroke, MI, and mortality risks in women with T2DM, regardless of menopausal status. The highest effects of aHR compared to the sedentary group were 0.68 for stroke, 0.66 for MI, and 0.81 for mortality. Postmenopausal women experienced significant MI risk reductions at most exercise intensities, with the greatest reduction in the ≥1,500 metabolic equivalent of task score group unlike premenopausal women. However, stroke and mortality risk reductions in postmenopausal women were less pronounced compared to premenopausal women. Conclusion Exercise reduces CCVD risk in women with T2DM across menopausal status. Postmenopausal women with T2DM had more benefits from exercise on MI but fewer benefits on stroke and mortality than premenopausal women. In premenopausal women with T2DM, exercise was not associated with a lower MI risk.

Objective: The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has been proposed to be a downstream mediator of neuroinflammation in individuals with Parkinson’s disease (PD). However, its involvement across disease stages and related synucleinopathies, such as multiple system atrophy (MSA), remains unclear. We aimed to analyze the peripheral mRNA expression of NLRP3-related genes and cytokines across individuals with isolated REM sleep behavior disorder (iRBD), early-stage PD, late-stage PD, and MSA. Methods: Peripheral blood mononuclear cells (PBMCs) were collected from 151 participants: 35 healthy controls (HCs), 31 patients with iRBD, 41 patients with early-stage PD, 21 patients with late-stage PD, and 23 patients with MSA. mRNA expression was measured using quantitative real-time polymerase chain reaction. Statistical comparisons were performed using analysis of variance (ANOVA) or Welch’s ANOVA, and associations with clinical variables were analyzed through stepwise multiple linear regression. Results: NLRP3 expression was significantly lower in patients with iRBD (p=0.0263) and patients with early-stage PD (p= 0.0101) than in HCs. NIMA-related kinase 7 (NEK7) expression progressively decreased across the disease spectrum (HCs vs. patients with early-stage PD, p=0.0008; vs. patients with late-stage PD, p<0.0001). In contrast, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and caspase-1 were elevated in patients with PD, especially those in the late stages. Levels of patients with MSA resembled those of HCs but differed from those of patients with PD. Interleukin (IL)-1β and IL-18 levels were not significantly different. In patients with early-stage PD, NLRP3 expression was negatively correlated with disease duration, the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale Part II score, and the cognitive score. Conclusion Our findings challenge the prevailing hypothesis that NLRP3 inflammasome activation directly contributes to PD pathogenesis. Instead, the observed increase in ASC and caspase-1 expression suggests the potential involvement of alternative inflammasome pathways during disease progression.

Background: The prevalence of diabetes mellitus and early-onset dementia (EOD), defined as dementia diagnosed at an age <65 years, is increasing worldwide, with significant socioeconomic implications. We investigated the association between diabetes, prediabetes, and EOD, focusing on the influence of diabetes duration on EOD risk. Methods: Using the Korean National Health Insurance Service database, we analyzed data from 1,979,509 patients aged 40–60 years who underwent health checkups in 2009. Patients were categorized into five groups: normal, impaired fasting glucose (IFG), newly diagnosed diabetes, diabetes duration <5 years, and diabetes duration ≥5 years. Cox proportional hazard models were used to estimate the adjusted hazard ratios (aHRs) for EOD after adjusting for demographic and clinical covariates. Results: During the observation period (mean 7.75 years), 8,921 patients with EOD were identified. The diabetes group demonstrated a significantly higher incidence of EOD compared to the normal group (aHR, 1.334; 95% confidence interval [CI], 1.226 to 1.451). EOD risk increased with longer diabetes duration, with the highest risk observed in patients with diabetes ≥5 years (aHR, 1.543; 95% CI, 1.368 to 1.741). No significant difference was observed between the IFG and normal groups (aHR, 0.989; 95% CI, 0.938 to 1.043). Additionally, the hypertension group exhibited a significantly higher incidence of EOD compared to the non-hypertension group (aHR, 1.364; 95% CI, 1.291 to 1.442). Conclusion Diabetes is independently associated with increased risk of EOD, and this risk increases with longer diabetes duration. This association remained significant regardless of the presence and duration of hypertension.

Background: Left bundle branch block (LBBB) significantly increases the risk of left ventricular systolic dysfunction (LVSD) due to cardiac dyssynchrony. Although artificial intelligence–enabled electrocardiography (AI-ECG) mod‑ els show promise in detecting LVSD, their performance in LBBB patients remains underexplored. We hypothesized that an AI-ECG model clinically validated for detecting LVSD would accurately detect LVSD and predict future clinical outcomes in LBBB patients. Methods: In this retrospective multicenter study, 5,689 expert-validated LBBB ECGs collected from 2,813 patients between 2016 and 2024 were analyzed using a previously developed and validated AI-ECG model. LVSD was defined as an ejection fraction of ≤ 40%. Model performance was assessed using the area under the receiver operating char‑ acteristic curve (AUROC), the area under the precision-recall curve (AUPRC), sensitivity, and specificity. Patients were stratified into high- and low-risk groups based on a threshold that achieved 90% sensitivity. A Kaplan–Meier analysis was used to compare clinical outcomes. Results: Among the 2,813 LBBB patients (mean age, 70.7 years; male sex, 43.7%), hypertension and a history of heart failure were common. The AiTiALVSD model showed strong diagnostic performance for LVSD (AUROC, 0.930 [95% CI, 0.924–0.937]; AUPRC, 0.913 [95% CI, 0.902–0.923]; sensitivity, 0.979; specificity, 0.473). During the mean follow-up of 4.1 years, high-risk patients had significantly higher hazards than low-risk patients for all-cause mortality (adjusted hazard ratio [HR], 1.87; 95% CI, 1.53–2.28), implantable cardioverter defibrillator/cardiac resynchronization therapy implantation (adjusted HR, 15.2; 95% CI, 7.51–30.77), and cardiovascular hospitalization (adjusted HR, 1.11; 95% CI, 0.96–1.28). Conclusions AiTiALVSD effectively detects LVSD and stratifies long-term cardiovascular risk in LBBB patients, support‑ ing its clinical utility for early detection and patient management.

Vaccines are highly effective, but rare or delayed adverse events following immunization (AEFIs) require post-licensure surveillance beyond clinical trials. Korea lacks a comprehensive, active, database-based framework, yet key assets exist: nationwide claims databases (National Health Insurance Service/Health Insurance Review and Assessment Service), the national immunization registry (Korea Disease Control and Prevention Agency’s Immunization Registry Information System) for National Immunization Program (NIP) and non-NIP vaccines, and increasingly standardized hospital electronic health records.We propose a federated, code to data architecture with data linkages between these data.Implementation should adopt a common data model (CDM), standardized case definitions, latency accounting, and transparent public reporting under strong privacy governance. Major challenges include multi step administrative approvals for data linkage, incomplete capture of adult non-NIP vaccinations, heterogeneous hospital data structures, and strict data protection constraints. Strategic priorities are to streamline statutory and administrative processes for public health use, mandate or enable claims-based capture of adult vaccinations, enhance CDM based interoperability, and develop secure hubs for aggregated outputs. With these measures, Korea will be well positioned to establish a scalable active surveillance system capable of detecting rare AEFIs, supporting transparent and evidence-based communication, and ensuring equitable injury compensation grounded in domestic data.

Purpose: This study evaluated the clinical outcomes and prognostic factors in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced pancreatic cancer (LAPC) treated with upfront FOLFIRINOX followed by local-regional therapy (LRT), surgical resection (SR), and radiotherapy (RT). We aimed to identify specific patient subgroups for which RT may serve as a reasonable alternative to SR for local tumor control. Methods: We retrospectively analyzed 116 patients (SR group, n= 70; RT group, n= 46) at a single center between 2015 and 2020. Survival outcomes were compared based on LRT modalities, focusing on identifying subgroups in which RT provided an efficacy comparable to that of SR. Results: Among 116 patients, the SR group achieved a significantly higher 5-year overall survival (OS) than the RT group (27.1% vs. 8.7%, P< 0.0001), despite similar progression-free survival (P= 0.23). Significant prognostic factors for OS included carbohydrate antigen 19-9 (CA19-9) response in BRPC (P= 0.02) and radiologic partial response in LAPC (P= 0.05). Subgroup analysis revealed that, while SR provided a survival advantage in CA19-9 responders, no significant difference in OS was observed between SR and RT in CA19-9 non-responders (P= 0.37). Conclusion Although surgery remains the gold standard, RT may be considered a justifiable local alternative for CA19-9 non-responders and surgically ineligible patients with LAPC, yielding comparable outcomes in these specific, biologically unfavorable subgroups.

Objectives: In May 2025, clusters of salmonellosis were identified in 7 cities in the Republic of Korea, all associated with consumption of identical bakery products. This investigation aimed to characterize the outbreak, identify potential contributing factors, and inform strategies for preventing similar multi-facility foodborne outbreaks. Methods: A case series study was conducted among individuals who consumed Manufacturer H’s Product I and Product II on May 15–16, 2025 at 7 facilities (n = 1,235). Clinical specimens from symptomatic individuals, retained food samples, and environmental samples were collected and tested. Food-exposure histories were assessed, and active case finding was implemented across all supplied facilities. Traceback investigations were conducted at the manufacturer, distributor, and egg farms. Human and food isolates underwent pulsed-field gel electrophoresis (PFGE) and whole-genome sequencing (WGS). Results: A total of 323 cases met the outbreak case definition (attack rate, 26.2%), of which 48 were laboratory-confirmed. Salmonella Enteritidis was isolated from both clinical specimens and retained bakery products. PFGE patterns were indistinguishable between human and food isolates, and WGS demonstrated high genetic relatedness. These findings confirmed a common-source outbreak linked to the implicated bakery products. Conclusion This outbreak underscores the value of integrating epidemiological investigation, active case finding, and molecular typing to identify common food vehicles in outbreaks involving widely distributed manufactured foods. Coordinated collaboration between public health and food safety authorities is essential for the effective detection, response, and prevention of multi-facility foodborne outbreaks.

Purpose: The chromodomain helicase DNA-binding (CHD) protein family comprises adenosine triphosphate-dependent chromatin remodelers that regulate chromatin structure and gene expression. Pathogenic CHD2 variants are associated with neurodevelopmental phenotypes, but these genotype–phenotype correlations remain unclear. This study aimed to delineate the clinical and genetic features of patients with CHD2-related disorders and to explore the associated genotype–phenotype relationships. Methods: Among 22 patients with pathogenic or likely pathogenic CHD2 variants identified using a customized 172-gene neurodevelopmental and epilepsy panel, 19 with sufficient clinical data were included. Demographic, clinical, neuroimaging, electroencephalographic, and genetic data were retrospectively reviewed. Results: Eighteen pathogenic or likely pathogenic variants were identified, including eight novel variants: nine nonsense (50.0%), five splice-site (27.8%), two missense (11.1%), and two exon deletions (11.1%). All patients had epilepsy, with a median age of seizure onset of 2.33 years. Comorbidities included global developmental delay (89.5%), intellectual disability (82.0%), and neuropsychiatric symptoms (47.4%). Seizure types were heterogeneous, with a predominance of generalized-onset seizures, and 13 patients (68.4%) achieved seizure freedom. Marked phenotypic variability was observed: two unrelated patients with the same truncating variant had different developmental and seizure-related profiles, a symptomatic child with an inherited exon 5 deletion contrasted with her asymptomatic father, and a patient with an exon 17–29 deletion exhibited relatively mild features. Conclusion Epilepsy was a consistent manifestation in this study and was accompanied by diverse developmental and neurobehavioral features, with substantial genotype–phenotype discordance. Further research on genotype–phenotype correlation is warranted.

Background: Older patients aged ≥75 years are underrepresented in major statin trials, leaving the optimal statin intensity after acute ischemic stroke (AIS) undefined. We aimed to compare functional outcomes and short-term safety between high-intensity statin therapy (HIST) and moderate-intensity statin therapy (MIST) in patients aged ≥75 years with AIS or transient ischemic attack. Methods: Using a prospective stroke registry at a single tertiary center (2019–2022), we retrospectively analyzed 337 patients aged ≥75 years with AIS or transient ischemic attack who maintained statin therapy for 3 months (HIST n=117; MIST n=220). The primary outcome was a favorable 3-month functional outcome (modified Rankin Scale score 0–2). Secondary outcomes included stroke recurrence, adverse effects, and statin discontinuation. Multivariable logistic regression with pre-specified sensitivity analyses was performed. Results: Favorable outcomes at 3 months were more frequent with HIST (70.9% vs. 55.9%; p=0.010). After multivariable adjustment, HIST was independently associated with a favorable outcome (adjusted odds ratio [aOR]=2.03, 95% confidence interval [CI] 1.17–3.53), consistent across sensitivity analyses: per-protocol (aOR=3.48, 95% CI 1.97–6.17) and atrial fibrillation-adjusted (aOR=2.21, 95% CI 1.26–3.89). No significant differences were observed in statin discontinuation, stroke recurrence, or adverse effects. Conclusion In older patients with AIS, HIST was independently associated with better functional outcomes without evidence of increased harm, broadly consistent with current guideline recommendations for HIST when tolerated. Prospective studies are needed to confirm a causal relationship.