Purpose: Although gastric cancer (GC) exhibits significant genomic heterogeneity, the clinical implications of its immune microenvironment remain poorly understood. Materials and Methods: We retrospectively evaluated patients with GC who underwent gastrectomies between 2011 and 2014. The tumors were analyzed for Epstein–Barr virus (EBV), microsatellite instability-high (MSI-H), tumor-infiltrating lymphocytes (CD3), tumor-associated macrophages (CD68 and CD163), and programmed death-ligand 1 (PD-L1) expression. Tumors were classified using the modified The Cancer Genome Atlas scheme, and their clinical characteristics were compared. Results: A total of 567 patients were classified into EBV (6%), MSI-H (10%), chromosomal instability-like (36%), and genomically stable-like (48%) subtypes. EBV tumors exhibited the highest PD-L1 expression (85%) and immune infiltration by CD3+ T cells (86%), CD68+ macrophages (58%), and CD163+ macrophages (40%). High CD68+ macrophage tumors were associated with advanced stages and worse 5-year disease-free survival (83% vs. 95%; P<0.001);however, this association was not independently significant after adjusting for the tumor-nodemetastasis stage. PD-L1 expression did not significantly affect the survival outcomes. Conclusions GC subtypes have distinct immune microenvironments that influence prognosis. Our findings highlight the prognostic and therapeutic potential of immune profiling in GC.

This study aimed to describe a facet-preserving modified transpedicular unilateral biportal endoscopic (UBE) approach for upwardly migrated thoracic disc herniation that allows safe decompression without spinal cord retraction or postoperative instability. Thoracic disc herniation is rare but often symptomatic, producing myelopathy that typically necessitates surgical intervention. Because of the spinal cord’s close proximity, traditional discectomy approaches carry a high risk of neural injury, and achieving complete disc removal without cord manipulation remains a significant surgical challenge. Although several techniques have been proposed, many are limited by the potential for incomplete decompression or iatrogenic instability. A facet-preserving modified transpedicular UBE approach may overcome these limitations by offering a minimally invasive surgical corridor while maintaining spinal stability. A 76-year-old woman presented with progressive bilateral lower extremity weakness and numbness over 6 months, with rapid deterioration during the past month. Magnetic resonance imaging (MRI) revealed an upwardly migrated thoracic disc herniation at T10–11 compressing the spinal cord. A UBE discectomy using a facet-preserving modified transpedicular approach was performed. The herniated fragment was completely removed without spinal cord retraction. Postoperatively, the patient demonstrated neurological improvement without complications. MRI confirmed complete decompression of the cord, and computed tomography verified preservation of the facet joint. This video article introduces the modified transpedicular UBE approach as a safe and precise minimally invasive technique for thoracic ventral pathologies. By enabling direct ventral decompression while preserving spinal stability, it broadens the scope of endoscopic spine surgery and warrants further clinical validation.

Background/Aims: Potassium-competitive acid blockers (P-CABs) have emerged as promising alternatives to proton pump inhibitors (PPIs) to treat erosive esophagitis (EE). This study aims to compare the efficacy and safety of P-CABs and PPIs in patients with mild to severe EE stratified by treatment phase. Methods: A systematic literature search was conducted using PubMed, MEDLINE, and the Cochrane Central Register of Controlled Trials. Randomized controlled trials comparing the efficacy of P-CABs and PPIs for EE were included. The pooled risk ratios (RRs) and risk differences with 95% confidence intervals (CIs) were calculated. A frequentist network meta-analysis was performed, and treatment ranking was assessed using P-scores. Results: Nineteen studies evaluating 5 P-CABs (vonoprazan, tegoprazan, keverprazan, fexuprazan, and zastaprazan) and 2 PPIs (lansoprazole and esomeprazole) were included. P-CABs demonstrated superior efficacy in healing EE during the initial phase, particularly in patients with severe EE (RR = 1.10; 95% CI, 1.00-1.20) and were also associated with a lower EE recurrence risk during maintenance treatment (RR = 0.59; 95% CI, 0.41-0.85). The efficacy was notably greater in patients with higher EE severity and among cytochrome P450 2C19 extensive metabolizers. The safety profiles of the P-CABs and PPIs were comparable. Vonoprazan consistently ranked the highest for both initial treatment (P-score = 0.68) and maintenance (P-score = 0.94). Conclusions P-CABs, especially vonoprazan, showed superior efficacy compared to PPIs in both the initial and maintenance treatment of EE. These findings support the use of P-CABs as a potent and reliable first-line option for EE management, particularly in high-risk populations, with acceptable safety outcomes.

Gastroesophageal reflux disease (GERD) is a chronic and relapsing gastrointestinal disorder characterized by the reflux of gastric contents into the esophagus, leading to troublesome symptoms and/or complications. Since the publication of the 2020 Seoul Consensus on GERD, significant new evidence has emerged, particularly regarding acid-suppressive therapies and diagnostic approaches. This 2025 focused update aims to refine GERD management strategies by incorporating the latest evidence on acid suppressive therapies and regional considerations in Asian populations. This study builds on the 2020 Seoul Consensus by integrating systematic reviews, meta-analyses, and expert consensuses to offer updated recommendations for the definition and medical treatment of GERD. These guidelines incorporate recent advances in acid-suppressive therapies, particularly potassium-competitive acid blockers, and adopt updated diagnostic frameworks in accordance with the Lyon Consensus 2.0. Key clinical questions were identified and structured using the following format: Population, Intervention, Comparator, Outcome. The resulting recommendations address the initial treatment, long-term maintenance strategies, and role of personalized therapy based on disease severity, such as the grade of reflux esophagitis. Six key statements are presented: updated definition and classification of GERD (Statement 1); initial and long-term treatment strategies tailored to GERD phenotypes, such as non-erosive reflux disease, mild erosive esophagitis, and severe erosive esophagitis (Statements 2-5); and dose optimization strategies for long-term safety (Statement 6). These guidelines aim to support gastroenterologists and general healthcare providers in making individualized evidence-based decisions for GERD management.

BACKGROUND/OBJECTIVES: This study evaluated the anti-adipogenic effects of skim milk hydrolysate with alcalase and prozyme (SMH-AP) in 3T3-L1 cells and identified its bioactive peptides.MATERIALS/METHODS: After adipogenic differentiation, 3T3-L1 adipocytes were treated with SMH-AP. RESULTS: SMH-AP, produced via sequential hydrolysis with Alcalase and Prozyme, significantly inhibited lipid accumulation and modulated adipogenic and lipogenic biomarkers. It downregulated CCAAT/enhancer-binding protein (C/EBP) β, C/EBPα, peroxisome proliferator-activated receptor gamma, and sterol regulatory element-binding protein (SREBP) 1c, while upregulating Krüppel-like factor 2. SMH-AP suppressed the cholesterogenic markers (SREBP2 and 3-hydroxy-3-methylglutaryl-coenzyme A reductase) and activated AMP-activated protein kinase alpha, which phosphorylated acetyl-CoA carboxylase and activated hormone-sensitive lipase.Molecular analysis confirmed extensive proteolysis into small, cell-permeable peptides (~330 Da). Liquid chromatography–mass spectrometry/mass spectrometry identified Ala–Val–Pro– Tyr–Pro and Gly–Leu–Pro–Gln–Glu as major bioactive peptides. CONCLUSION These findings suggest that SMH-AP may serve as a promising functional food ingredient for preventing obesity.

Alzheimer’s disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depressionlike behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer’s disease and depression.Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.

In patients with differentiated thyroid cancer (DTC), initial recurrence risk stratification based on clinical, histopathological, and perioperative data remains the key determinant for guiding management strategies during the first 1-2 years post-treatment. However, the adoption of ongoing risk stratification (ORS), which dynamically reassesses risk by integrating longitudinal clinical data and treatment response, enables more precise long-term prognostic assessment and facilitates highly individualized management. Building upon recent guidelines, the 2026 KTA guideline has been further refined by incorporating robust evidence from large-scale national cohorts and comprehensive systematic reviews. These updated recommendations outline contemporary concepts of ORS, risk-adapted TSH suppression targets, optimized surveillance modalities for recurrence detection, and disease-specific long-term follow-up strategies. Reflecting the paradigm shift toward de-escalated treatment, this revision integrates evolved perspectives on TSH suppression intensity, the clinical interpretation of thyroglobulin levels, and tailored follow-up intervals. These evidence-based recommendations aim to minimize unnecessary treatment and excessive surveillance in the large proportion of patients with excellent prognosis after initial therapy, while ensuring that each patient receives appropriately tailored and effective long-term management.

Purpose: Based on the KEYNOTE-522 study, neoadjuvant pembrolizumab plus chemotherapy has become the standard treatment for early-stage triple-negative breast cancer (TNBC).This study evaluated the real-world efficacy, safety, and predictors of pathologic complete response (pCR) in Korean patients. Methods: We conducted a retrospective cohort study of 174 patients with early-stage TNBC who received the KEYNOTE-522 regimen (neoadjuvant pembrolizumab plus paclitaxel and carboplatin, followed by doxorubicin and cyclophosphamide) at a tertiary cancer center between August 2022 and July 2024. We assessed the primary endpoints, including pCR rate and event-free survival (EFS). We performed univariable and multivariable logistic regression analyses to identify independent predictors of pCR. Results: The median patient age was 50 years (range, 24–74 years). The clinical stages were II and III in 79.3% and 20.1% of patients, respectively, and 10.9% had clinical N3 disease. The overall pCR rate was 62.1%, and the N3 subgroup had a pCR rate of 47.4%. On multivariable analysis, high baseline Ki-67 expression (≥ median, 75%) was significantly associated with pCR (odds ratio, 2.84; 95% confidence interval, 1.45 to 5.66; p = 0.002). At a median followup of 18.4 months, the 12-month EFS rate was 97.4%, with significantly superior outcomes observed in patients who achieved pCR compared with those who did not achieve pCR (100% vs. 93.1%, p = 0.007). The treatment completion rate was 92.0%, and immune-related adverse events occurred in 13.8% of patients. Conclusion In this real-world analysis of one of the largest Asian cohorts of patients with earlystage TNBC treated with neoadjuvant pembrolizumab, the KEYNOTE-522 regimen demonstrated substantial efficacy and manageable toxicity, consistent with the original trial findings.

Objective: Recognizing discrimination as a significant public health risk during the coronavirus disease 2019 (COVID-19) pandemic, which coincided with increased drug use and heightened awareness of structural disparities in the United States, we investigated its association with the odds of drug use in a large and diverse cohort from the All of Us Research Program. Methods: In this cross-sectional study, data from 68,976 participants completed the COVID-19 participant experiences (COPE) survey. We applied logistic regression models with propensity score-based overlap weighting to examine associations between everyday discrimination and drug use. Self-reported everyday discrimination score and drug use were the primary exposure and outcome measures, respectively. Results: Of the 67,662 COPE respondents (mean [standard deviation] age, 57.5 [15.9] years; female sex at birth, 43,658 [64.5%]), we identified 15,493 participants with no reported discrimination and 15,493 participants with reported discrimination, after overlap weighting. The odds of drug use in those who reported discrimination was 1.38 (95% confidence interval, 1.32–1.43), with a dose-dependent association based on discrimination score. Participants who experienced discrimination had significantly higher odds of using drugs and this association was particularly pronounced in those under 40 years of age, those assigned female sex at birth, current smokers, individuals undergoing chemotherapy or immunotherapy, and those experiencing unemployment or COVID-19/flu-like symptoms. Conclusion This relationship was observed across various types of drugs and different reasons for discrimination, and it was particularly pronounced in specific subgroups. These findings provide critical evidence for developing targeted preventive interventions; however, further longitudinal studies for causality are warranted.

Purpose: The current study provides national cancer statistics and their secular trends in Korea, including incidence, mortality, survival, and prevalence in 2023, with international comparisons. Materials and Methods: Cancer incidence, survival, and prevalence rates were calculated using the Korea National Cancer Incidence Database (1999-2023), with survival follow-up until December 31, 2024. Mortality data were obtained from the Ministry of Data and Statistics, while international comparisons were based on GLOBOCAN data. Results: In 2023, 288,613 newly diagnosed cancer cases (age-standardized rate [ASR], 288.6 per 100,000) and 85,271 deaths from cancer (ASR, 64.3 per 100,000) were reported. Among the incident cases, 145,452 (50.4%) were aged 65 years or older. Prostate cancer became the most common cancer among men for the first time. The proportion of localized-stage cancers increased from 45.6% in 2005 to 51.8% in 2023. Korea had the lowest cancer mortality among countries with similar incidence rates and the lowest mortality-to-incidence ratios for stomach, colorectal, and breast cancer. The 5-year relative survival rate (2019-2023) was 73.7% overall and 92.7% for localized-stage cancers. Over 2.73 million prevalent cases were identified in 2023, representing 5.3% of the Korean population. Conclusion These findings indicate that Korea’s cancer control efforts have contributed to early detection and improved survival outcomes. As Korea enters a super-aged society in 2025, cancer burden will continue to increase, requiring sustained and adaptive cancer control strategies.