BACKGROUND/OBJECTIVES: Lutein, a dietary carotenoid, plays a crucial role in protecting eye health as an anti-inflammatory agent and antioxidant. Green leafy vegetables constitute a major source of lutein; however, comparative studies on different consumption methods are limited. Therefore, this study aimed to evaluate the bioavailability of lutein from lutein-rich foods, namely, raw vegetables and raw vegetable juice. SUBJECTS/METHODS: In this study, 18 adults were recruited. They were randomly divided into three groups: commercial lutein supplement (LUT, 20 mg), raw vegetable (RV), and raw vegetable juice (RVJ) groups. Blood was collected at 0-, 4-, 6-, 8-, 12-, 24-, and 30-h intervals after the consumption of each test meal. Participants’ serum lutein levels were analyzed using high-performance liquid chromatography (HPLC). Considering lutein’s wellestablished anti-inflammatory properties, changes in inflammatory status were assessed by measuring serum high-sensitivity C-reactive protein (hs-CRP) levels. Furthermore, urinary metabolomic profiling was conducted using 1 H nuclear magnetic resonance spectroscopy to evaluate metabolic alterations. RESULTS: After consuming each lutein-rich food, participants’ blood lutein levels were analyzed, and the serum concentration peaked at 12 h (0.37 ± 0.13 μg/mL), 24 h (0.61 ± 0.18 μg/mL), and 30 h (0.42 ± 0.16 μg/mL) after RV, LUT, and RVJ consumption, respectively.Additionally, hs-CRP levels decreased following lutein-rich food consumption. Twelve hours after consumption, hs-CRP levels decreased to 0.81 and 0.83 mg/L in the RV and RVJ groups, respectively. Twenty-four hours after consumption, they further decreased to 0.68 and 0.74 mg/L in the LUT and RVJ groups, respectively. Thirty hours after consumption, a reduction to 0.61 mg/L was observed in the RVJ group. Furthermore, after consuming each luteinrich food, N-acetyl glycoprotein levels decreased at 24 h, reflecting metabolic alterations potentially associated with lutein metabolism. CONCLUSION These findings suggest that the short-term consumption of lutein-rich foods, regardless of their type or source, potentially yields health benefits.

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.

Purpose: Molecular characteristics of synchronous colorectal cancers (SCRCs) remain incompletely elucidated, despite their importance in targeted therapy selection. We compared the molecular characteristics and somatic mutations between SCRCs. Materials and Methods: This retrospective study (2012-2014) included 98 consecutive patients with surgically resected SCRCs. Molecular characteristics, including microsatellite instability (MSI) and tumor-infiltrating lymphocytes (TILs), were analyzed for all cancer lesions. The intertumoral heterogeneity of SCRCs was evaluated using whole-exome sequencing (WES) for 18 cancers from nine patients with at least one MSI-high (MSI-H) tumor. Results: Twelve patients had at least one MSI-H tumor; five showed discordant MSI status. Mucinous adenocarcinoma frequency and TIL density were higher in patients with at least one MSI-H tumor than in those with only microsatellite-stable tumors. WES revealed that, except one patient (6.5%), most synchronous cancers shared few variants in each patient (0.09%-0.36%). The concordance rates for BRAF, KRAS, NRAS, and PIK3CA, in synchronous cancers from each patient were 66.7%, 66.7%, 66.7%, and 55.6%, respectively. Conclusion Although synchronous cancers shared a mutated gene, the mutation subtypes differed. SCRCs exhibited 5.1% MSI status discordance rate and a high discordance rate in somatic mutational variants. As intertumoral heterogeneity may affect the targeted therapy response, molecular analysis of all tumors is recommended for patients with SCRCs.

Objectives: . Obstructive sleep apnea (OSA) is associated with chronic intermittent hypoxia and systemic inflammation, both of which contribute to vascular and metabolic complications. Monocytes, as key immune cells of innate immunity, have been implicated in this inflammatory state. However, the effect of OSA treatment on monocyte function and inflammatory phenotype remains poorly understood. Methods: . In this prospective cohort study, OSA patients were evaluated before and after 3 months of continuous positive airway pressure (CPAP) therapy. Circulating monocytes were isolated, and inflammatory cytokine production (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, and IL-6) was assessed at baseline and post-treatment, both at rest and after lipopolysaccharide (LPS) stimulation. Monocyte polarization (M1/M2-like marker expression) was measured by flow cytometry. Clinical severity parameters, including the apnea-hypopnea index (AHI) and oxygen desaturation index (ODI), were correlated with immune changes. Results: . Following CPAP treatment, LPS-induced inflammatory cytokine secretion and LPS responsiveness, defined as the increase in cytokine levels upon stimulation, both declined after CPAP in proportion to baseline ODI, but not AHI. Apart from TNF-α, baseline IL-1β and IL-6 levels were below the quantifiable range of the assay, which precluded reliable comparison after treatment. This effect may be explained by a parallel post-treatment shift in monocyte phenotype toward an anti-inflammatory M2-like (CD163+CD206+) profile, as demonstrated by our flow cytometry data, which was also significantly associated with baseline ODI. Conclusion . CPAP alleviates systemic inflammation in OSA by reducing hypoxic burden and reprogramming monocytes toward an anti-inflammatory phenotype. The magnitude of immune modulation was more closely linked to ODI than AHI, suggesting that oxygen desaturation burden serves as a meaningful adjunct to AHI in assessing monocyte-driven immune dysregulation in OSA.

Background: and Purpose Although gastrointestinal (GI) surgery can affect drug efficacy, its impact on oral anticoagulants (OACs) remains unclear. This study investigated the impact of GI surgery on the comparative effectiveness and safety of direct oral anticoagulants (DOACs) versus warfarin in atrial fibrillation (AF). Methods: Using a nationwide South Korean claims database, AF patients prescribed OACs between 2015 and 2021 were analyzed. The primary outcome was ischemic stroke, and secondary outcomes were major bleeding, all-cause death, and composite outcome (ischemic stroke, major bleeding, all-cause death). Outcomes were compared by OAC type (DOAC vs. warfarin) and GI surgery status using inverse probability of treatment weighting and a Fine–Gray subdistribution hazard model with time-varying covariates. Results: Among 388,214 AF patients (mean age, 71.9 yr; 42.7% male), 6,907 (1.8%) underwent GI surgery. The effect of GI surgery differed between warfarin and DOACs for ischemic stroke (Pint= 0.018), with increased risk for warfarin (adjusted HR [aHR]: 2.32; 95% confidence interval [CI] 1.17–4.62), but not for DOACs (aHR: 0.97 [95% CI 0.77–1.22]) after surgery. Effects of surgery on major bleeding, all-cause death, and composite outcome did not differ. In post–GI surgery setting, DOACs demonstrated lower ischemic stroke risk (aHR: 0.35 [95% CI 0.17–0.72]) and comparable risks for other outcomes. Exploratory analyses by surgery location suggested a more favorable profile of DOACs after upper GI surgery. Conclusions In AF patients, GI surgery significantly increased ischemic stroke risk among warfarin users, but not among DOAC users. DOACs showed generally favorable profiles after GI surgery and may remain a reasonable anticoagulant, with potentially more favorable profile after upper GI surgery.

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.

Although venous invasion (VI) is associated with distant metastasis and observed in >50% of pT2–4 colorectal cancers (CRCs), the role of VI in pT1 CRCs is not well-defined. Methods: Thirty-four surgically resected pT1 CRCs were reevaluated for 2-dimensional (2D) VI using hematoxylin and eosin (H&E)–stained slides with additional elastic and desmin immunohistochemical staining (cohort A). Additionally, 27 pT1 CRCs without knowing VI status were selected for 3-dimensional (3D) VI evaluation only (cohort B). All 61 cases (cohorts A and B) were studied in 3D using tissue clearing. Results: VI was detected more commonly in 3D (17/34, 50.0%) than in 2D H&E slide evaluation (9/34, 26.5%, p = .047). When VI was identified in 3D (27/61, 44.3%), the most common phase was that of intraluminal growth (22/27, 81.5%), followed by intravasation (7/27, 25.9%) and extravasation (5/27, 18.5%). E-cadherin expression was characterized in 3D in foci of VI and varied in each phase of invasion. Conclusions: All three phases were observed in VI of pT1 CRCs. The extravasation of neoplastic cells from foci of VI in pT1 CRC suggests that VI could be a route of intratumoral spreading in a subset of pT1 CRCs.

Janus kinase (JAK) inhibitors are an important treatment option for ulcerative colitis, providing rapid onset of action, oral administration, and efficacy even after biologic failure. The 3 approved agents—tofacitinib, filgotinib, and upadacitinib—differ in JAK isoform selectivity, leading to clinically meaningful differences in efficacy and safety. Evidence from network meta-analyses, clinical trials, and real-world studies consistently shows that upadacitinib provides the highest efficacy for induction and maintenance of remission, whereas filgotinib demonstrates the most favorable safety profile. The strong efficacy of upadacitinib and tofacitinib is particularly relevant in patients with severe disease, including acute severe ulcerative colitis, and upadacitinib maintains high efficacy regardless of prior advanced therapy exposure. JAK inhibitors also benefit extraintestinal manifestations. Although risks such as herpes zoster, serious infection, thromboembolism, and major cardiovascular events differ among agents, long-term data suggest generally acceptable safety when used appropriately. Intraclass JAK-to-JAK cycling is feasible, with about half of patients achieving steroid-free clinical remission in retrospective cohorts. Based on mechanistic, clinical, and real-world evidence, filgotinib may be a first-line option for patients with lower disease activity or when safety is a priority, whereas upadacitinib or tofacitinib may be preferred in higher disease activity. Strategically selecting agents may improve durability and outcomes.

Background and Objectives: Clinical characteristics and outcomes in acute heart failure (AHF) vary by phenotype. We assessed phenotype-specific features, treatment patterns, and outcomes in a nationwide Korean cohort. Methods: The Korean Heart Failure III registry prospectively enrolled 7,351 AHF admissions at 47 hospitals. Among 6,777 patients with available left ventricular ejection fraction (EF), phenotypes were defined as heart failure with reduced EF (HFrEF, ≤40%), mildly reduced EF (HFmrEF,41–49%), or preserved EF (HFpEF, ≥50%). The primary endpoint was a 12-month composite of all-cause death or heart transplantation, evaluated from index admission and, among hospital survivors, from discharge. We used inverse probability weighting (multinomial generalized boosted models with stabilized, trimmed weights) and weighted Cox proportional-hazards models to estimate hazard ratios (HRs). Results: Phenotype distribution was 58.9% HFrEF, 13.6% HFmrEF, and 27.5% HFpEF. Crude 12-month composite rates from index admission were 13.4% (HFrEF), 12.7% (HFmrEF), and 16.8% (HFpEF). After weighting, from index admission, HFmrEF (HR, 0.892; 95% confidence interval [CI], 0.731–1.088) and HFpEF (HR, 1.101; 95% CI, 0.939–1.291) did not differ from HFrEF; from discharge, HFpEF had modestly higher risk (HR, 1.207; 95% CI, 1.008–1.445) whereas HFmrEF did not (HR, 1.039; 95% CI, 0.844–1.279). Hyponatremia and chronic kidney disease were consistent adverse markers, while angiotensin-converting enzyme inhibitor/ angiotensin II receptor blocker use at discharge was protective. Conclusions Across the EF spectrum, phenotypes showed distinct profiles and risk. Postdischarge risk was modestly higher in HFpEF, supporting phenotype-tailored care and systematic discharge optimization in Korean patients with AHF.