Background/Aims: Various expanded criteria (EC) for liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) have been proposed to avoid the narrow nature of the Milan criteria (MC). To investigate which EC predicts more favorable outcomes in terms of overall survival (OS) and recurrence-free survival (RFS), we conducted a network meta-analysis (NMA). Methods: A database search was conducted on PubMed, Embase, and the Cochrane Library, to identify studies comparing OS and RFS between patients within the MC and those exceeding the MC but within the EC. Hazard ratios (HRs) were pooled using a random-effects NMA and validated in an in-house cohort of 1,008 LT recipients. Results: Among 22,466 articles identified, 35 studies with 45 pairwise comparisons were included in the NMA along with 8 different EC. The University of California San Francisco (HR, 1.43; 95% CI, 1.19–1.71), Up-to-Seven (HR, 1.50; 95% CI, 1.15–1.97), and Hangzhou criteria (HR, 1.69; 95% CI, 1.11–2.57) showed inferior OS to the MC. The MC ranked highest for both OS and RFS, followed by Metroticket 2.0 for OS and the Asan criteria for RFS. In the validation cohort, both Metroticket 2.0 and AFP model yielded more favorable HCC-specific mortality than other EC. Conclusions Several EC, of which those of Metroticket 2.0 were the best, yielded comparable outcomes to the MC. AFP-based EC such as Metroticket 2.0 and AFP model appeared to be useful in both the NMA and the validation cohort, suggesting a potential role in identifying selected low-risk patients beyond the MC.

The sixth edition of the Korean Medication Algorithm Project for Depressive Disorder (KMAP-DD) was published in 2025. This review compared KMAP-DD 2025 with four major international clinical practice guidelines: Canadian Network for Mood and Anxiety Treatments Clinical Guidelines for the Management of Major Depressive Disorders, National Institute for Health and Care Excellence Depression Guideline, Royal Australian and New Zealand College of Psychiatrists Clinical Practice Guidelines for Mood Disorders, and British Association for Psychopharmacology Guideline. While KMAP-DD is based on expert consensus, and others on evidence-based methods, overall treatment strategies for depressive episodes were fairly consistent. Especially, KMAP-DD 2025 offers more structured recommendations in areas lacking strong evidence, such as premenstrual dysphoric disorder, perinatal depression, and depression with medical comorbidities. KMAP-DD 2025 also reflected Korean clinical practice patterns emphasizing rapid symptom relief and early use of combination strategies. Despite limitations as a consensus-based guideline, KMAP-DD 2025 complements evidence-based approaches and provides practical, situation-specific guidance for real-world clinical decision-making in Korea.

Objective: This study examined whether baseline levels of 14 serum biomarkers predicted antidepressant remission differently by sex at 12 weeks and 12 months. Methods: In a prospective cohort, 1,086 outpatients with depressive disorders received stepwise antidepressant treatment following a naturalistic protocol. Baseline serum samples were analyzed for biomarkers from six systems: immune (high-sensitivity C-reactive protein, tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, interleukin-4, interleukin-10), metabolic (leptin, ghrelin, total cholesterol), neurotrophic (brain-derived neurotrophic factor), neurotransmitter (serotonin), endocrine (cortisol), and nutritional (folate, homocysteine). Remission, defined as a Hamilton Depression Rating Scale scores ≤ 7, was assessed at 12 weeks and 12 months. Logistic regression models with biomarker-by-sex interaction and stratified analyses were used, adjusting for clinical covariates. Results: Higher baseline serotonin predicted 12-week remission in males but not in females. At 12 months, lower leptin and higher folate predicted remission only in males, while lower cortisol predicted remission only in females. These showed significant biomarker-sex interactions. No sex-specific interactions were found for immune markers. Conclusion Baseline serum biomarkers across biological systems showed sex-specific associations with treatment outcomes. Neurotransmitter, metabolic, endocrine, and nutritional markers may offer predictive value for sex-tailored, biomarker-informed treatment strategies in depression.

OBJECTIVES: Kudoa septempunctata has been identified as the causative agent of food poisoning following the consumption of raw farmed Paralichthys olivaceus. However, cohort studies providing robust evidence for an association between K. septempunctata and gastrointestinal symptoms remain limited. This prospective cohort study investigated the association between the consumption of K. septempunctata–infected farmed P. olivaceus and the occurrence of gastrointestinal symptoms. METHODS: Individuals who purchased raw farmed P. olivaceus between 2020 and 2021 were selected as the study population. Study data included 2 rounds of questionnaire surveys administered before and after consumption, 2 muscle specimens obtained from each purchased fish, and human biological specimens collected from individuals who developed gastrointestinal symptoms within 24 hours after consumption. Data were analyzed using the chi-square test and t-test, and the association between consumption of K. septempunctata–infected farmed P. olivaceus and gastrointestinal symptoms was evaluated using relative risk estimates between exposure groups. RESULTS: The relative risk of gastrointestinal symptoms associated with exposure to K. septempunctata–infected P. olivaceus ranged from 71.2 (95% confidence interval [CI], 27.0 to 178.6) to 124.5 (95% CI, 43.5 to 355.0) across the 2 case definitions. A strong and statistically significant association was observed between exposure to K. septempunctata–infected P. olivaceus and the development of acute gastrointestinal symptoms. CONCLUSIONS These findings indicate both an association and a causal relationship between consumption of K. septempunctata–infected farmed P. olivaceus and the onset of gastrointestinal symptoms.

Mitochondrial bioenergetics plays a fundamental role in neuronal development and function. Prenatal exposure to corticosterone in rats (Corti.Pup) has previously been shown to cause delayed neurodevelopment and synaptic plasticity deficits, showing attention deficit hyperactivity disorder (ADHD) - like behaviors. However, the underlying mitochondrial metabolic adaptations remain unclear. This study investigated mitochondrial function and metabolic remodeling in prefrontal cortex neurons of Corti.Pups, focusing on oxidative phosphorylation, calcium handling, and redox balance. We assessed neuronal viability, reactive oxygen species (ROS) production, and oxygen consumption rate (OCR) through experiments conducted in both neuron-glia co-culture and neuron-only conditions. Furthermore, we evaluated electron transport chain (ETC) activity, mitochondrial membrane potential (MMP), and mitochondrial Ca2+ uptake in purified isolated mitochondria. In results, Corti.Pup neurons exhibited increased vulnerability to glutamate-induced excitotoxicity in the absence of glial support. Despite reduced ROS production, these neurons showed elevated mitochondrial OCR and proton leak, coupled with decreased non-mitochondrial OCR and ETC complex activity. Surprisingly, MMP remained elevated despite ETC dysfunction, and mitochondrial Ca2+ uptake was suppressed. These features indicate mitochondrial metabolic reprogramming, prioritizing MMP maintenance over ATP synthesis. The observed mitochondrial inefficiency and compensatory adaptations may impair energy production, contributing to delayed neuronal development in Corti.Pups. These findings suggest that mitochondrial dysfunction and metabolic remodeling play central roles in the pathogenesis of neurodevelopmental disorders such as ADHD.

Background and Objectives: Cardiac arrhythmia is highly prevalent in hypertrophic cardiomyopathy (HCM), but its relation to genotype has not been well established.We investigated the arrhythmia manifestations according to genotype in HCM patients. Methods: This single-center, retrospective study included 119 patients with HCM who underwent genetic testing using a next-generation sequencing panel. Incidence of cardiac arrhythmias and long-term outcomes were analyzed according to the presence of pathogenic variants (PVs). Results: PVs related to HCM were identified in 45 (37.8%) patients. Presentation of sustained ventricular tachycardia (VT) prior to HCM diagnosis was more prevalent in the PV-positive group. During a median follow-up of 45.9 months, the incidence of sustained VT was significantly higher in the PV-positive group (11.1% vs. 1.4%, hazard ratio, 8.71; 95% confidence interval, 1.02–74.61). A new implantable cardioverter defibrillator insertion rate was comparable in the 2 groups, but appropriate shocks were delivered in only 4 patients in the PV-positive group (8.9% vs. 0%, P = 0.037). Incidence of bradyarrhythmias requiring pacemaker and new-onset atrial fibrillation (AF) was not significantly different between the 2 groups. Among 56 patients with AF, there was no significant difference in treatment strategies in the 2 groups. However, sinus rhythm was maintained over the last 6 months of follow-up in 4/17 (23.5%) patients in the PV-positive group and 24/39 (61.5%) patients in the PV-negative group (P = 0.031). Conclusions Patients with PVs related to HCM exhibited higher incidence of life-threatening VTs. While overall AF incidence was similar between the groups, the presence of PVs was significantly associated with poorer rhythm outcomes of AF.

Background and Objectives: Circulating microRNAs (miRNAs) have been proposed as potential biomarkers in atrial fibrillation (AF) and heart failure (HF), but their role in patients with AF and heart failure with preserved ejection fraction (HFpEF) remains uncertain. Methods: We measured serum levels of 4 candidate miRNAs (miR-21, miR-146a, miR-146b, and miR-328) using quantitative polymerase chain reaction in 45 patients with persistent AF and HFpEF and five non-AF arrhythmia controls (Healthy). Expression levels were normalized to miR-16 and expressed as fold change (2−ΔCt ). Baseline (V1) and 3–6 months follow-up (V2) samples were analyzed, and comparisons were performed using non-parametric tests. Results: At baseline, none of the 4 miRNAs differed significantly between AF patients and Healthy controls; miR-21, 1.24 ± 0.55 vs. 1.15 ± 0.32 (P = 0.57); miR-146a, 0.66 ± 0.35 vs. 0.65 ± 0.06 (P = 0.71); miR-146b, 0.12 ± 0.07 vs. 0.11 ± 0.01 (P = 0.90); and miR-328, 0.08 ± 0.05 vs. 0.07 ± 0.03 (P = 0.95), all P > 0.5. Baseline comparisons were analyzed using relative expression values (2−ΔCt , normalized to miR-16), while longitudinal changes between V1 and V2 were assessed using fold change (2−ΔΔCt ). No significant longitudinal changes were observed across treatment groups. Conclusions In patients with persistent AF and HFpEF/HF with mildly reduced ejection fraction, circulating miR-21, miR-146a, miR-146b, and miR-328 showed no significant differences compared with the non-AF arrhythmia control group and did not change after 6 months of renin-angiotensin-aldosterone system-targeted therapy. These pilot data suggest that the short-term utility of biomarkers is limited and warrants validation in larger, randomized cohorts.

Background and Objectives: Primary prevention (PP) implantable cardioverter-defibrillator (ICD) therapy for ischemic cardiomyopathy (ICM) is underused in Asian countries, including South Korea. Both clinical and hospital factors may influence appropriate ICD use. We evaluated whether determinants of PP ICD implantation differ by hospital implantation volume. Methods: In this prospective, multicenter observational registry (blinded for review), patients eligible for PP ICD were enrolled. Factors associated with ICD implantation—clinical characteristics and hospital-level systems—were examined across 4 large-volume hospitals (≥ 15 implants during the study) and 12 small-volume hospitals (< 15). Multivariable logistic regression identified independent predictors. Results: Among 3,083 ICM patients (2,403 men; median age 70 years), PP ICD implantation rates were 10.8% in large-volume and 5.7% in small-volume hospitals. Across groups, male sex and chronic kidney disease independently predicted ICD implantation. Regarding hospital factors, non-monetary incentives for referral were the sole independent predictor in large-volume centers (odds ratio [OR], 3.55; 95% confidence interval [CI], 2.07–6.10;P < 0.001). In small-volume centers, heart failure conferences (OR, 12.73; 95% CI, 1.72–94.37;P = 0.013), structured education systems (OR, 11.72; 95% CI, 2.45–56.12; P = 0.02), and pacemaker clinics (OR, 11.4; 95% CI, 2.24–58.39; P = 0.003) were independently associated with implantation. Conclusions Clinical predictors of PP ICD use were consistent across hospital volumes, but hospital-level determinants differed. Referral incentives characterized large-volume centers, whereas conferences, education systems, and pacemaker clinics were key in smallvolume centers. Tailored institutional strategies by hospital volume may help close the PP ICD underuse gap and improve evidence-based implementation.

Background: and Objective: Obstructive sleep apnea (OSA) is increasingly recognized as a risk factor for cardiovascular diseases. However, long-term population-based evidence across a broad range of cardiovascular outcomes, particularly conduction system disorders, remains limited. We investigated the 15-year cardiovascular outcomes in patients with OSA using a large-scale nationwide cohort. Methods: This retrospective cohort study used the Korean National Health Insurance Service database, including 547,749 patients diagnosed with OSA and 2,282,415 matched controls between 2002 and 2020. Following exclusion criteria and 1:1 propensity score matching, 541,812 individuals were included in each group. The primary outcomes were incidence of atrial fibrillation (AF), premature beats, ventricular arrhythmias, atrioventricular (AV) block, sinus node dysfunction, heart failure, ischemic heart disease (IHD), and stroke. Cumulative incidence was assessed using Kaplan-Meier survival curves. Hazard ratios (HRs) were estimated using Cox proportional hazards models adjusted for relevant covariates. Results: Over a 15-year follow-up period, the OSA group exhibited significantly higher incidence rates for all cardiovascular outcomes than controls. In the matched cohort, adjusted HR were elevated for AF (1.82 [1.77–1.87]), premature beats (2.25 [2.17–2.34]), ventricular arrhythmias (1.81 [1.64–1.99]), AV block (1.81 [1.64–1.99]), sinus node dysfunction (2.22 [1.96–2.50]), heart failure (1.43 [1.39–1.48]), IHD (1.54 [1.52–1.56]), and stroke (1.20 [1.18–1.22]) (all P < 0.0001). Conclusions OSA was independently associated with an increased long-term risk of various cardiovascular outcomes, including arrhythmias, ischemic events, and conduction system disorders. This supports the importance of early identification and longitudinal management of cardiovascular risk in this population.

The brain-derived neurotrophic factor (BDNF) plays a crucial role in neuroprotection, and we have previously demonstrated BDNF-mediated neuroprotective effects in mesenchymal stromal cells (MSCs). The present study aimed to investigate whether BDNF-overexpressing MSCs enhance the therapeutic efficacy of naïve MSCs in a preclinical model of severe neonatal intraventricular hemorrhage (IVH). We exposed primary rat neuronal cells to 40 U of thrombin overnight in vitro. Subsequently, the neuronal cells were co-cultured with either naïve MSCs or BDNF-overexpressing MSCs (1×105 cells in 1 mL media) for 24 hours. Next, 300 μL of maternal blood was injected into bilateral ventricles on postnatal day (P)4 to induce severe IVH in newborn Sprague-Dawley male rats. At P6, either naïve MSCs or BDNF-overexpressing MSCs (1×105 cells in 10 μL saline) were transplanted intraventricularly. Behavioral function tests, including passive avoidance, followed by endpoint analyses of brain tissue and cerebrospinal fluid were performed at P35. BDNF-overexpressing MSCs enhanced the effects of naïve MSCs against cell death, cytotoxicity, and oxidative stress in vitro. Notably, naïve and BDNF-overexpressing MSCs did not attenuate post-hemorrhagic ventricular dilatation, neuronal cell death, or gliosis. However, BDNF-overexpressing MSCs attenuated microglial activation.Furthermore, inflammatory cytokine (interleukin [IL]-1α, IL-1β, IL-6, and tumor necrosis factor-α) levels and memory function assessed using a passive avoidance test significantly improved in the BDNF-overexpressing MSC transplanted group compared with the naïve MSC transplanted group. Our data suggest that BDNF-overexpressing MSCs may offer superior protective effects to naïve MSCs in a neonatal IVH model.