Background: Retinitis pigmentosa (RP) comprises a heterogeneous group of inherited retinal dystrophies. The genetic landscape of RP has been characterized; however, knowledge gaps regarding age-specific genetic variation trends in Korean patients remain. We comprehensively characterized the age-stratified genetic landscape of RP in Korean patients, with a focus on identifying novel mutational trends and clinically actionable insights. Methods: We performed targeted next-generation sequencing of 199 genes associated with RP and related disorders in a cohort of 403 unrelated patients clinically diagnosed as having RP. We analyzed the inheritance patterns, variation spectrum, and prevalence of pathogenic variants, stratifying the results by age, and conducted copy number variation (CNV) analysis. Results: A genetic diagnosis was achieved for 193 of the 403 patients (48%). The diagnostic yield was highest in patients diagnosed before 20 yrs of age (60%), with lower yields in older age groups. Although USH2A and EYS, the most common causative genes in autosomal recessive inheritance, were frequently identified, RPGR pathogenic variants accounted for a significantly larger proportion of genetically solved cases diagnosed before the age of 20 yrs (27%–28%) than in those with later-onset disease (9%–15%). CNVs were identified in 4% of genetically solved cases. Conclusions The results underscore distinct, age-related genetic contributions to RP in Korean patients, with RPGR variants demonstrating relevance in early-onset disease, and provide diagnostic insights to improve current practices. These findings can aid in prioritizing gene therapy targets and refining screening strategies.

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.

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.

Background: Baricitinib is one of the front-runners among targeted agents for the treatment of atopic dermatitis (AD). Although many studies have been conducted on the real-world use of baricitinib, the sample size is often small and data is focused primarily on Caucasians. Objective: The objective of this study was to demonstrate the real-world itch-relieving property of baricitinib in adult AD patients in South Korea. Methods: Electronic medical records of AD patients treated with baricitinib at the National Medical Center in Korea from May 2021 to April 2023 were analyzed retrospectively. Results: Seventy patients completed 16 to 52 weeks of baricitinib treatment, with most patients showing mild-to-moderate baseline lesions and moderate-to-severe baseline itch. At Week 16 of baricitinib treatment, there was a 50% reduction in Itch numerical rating scale from baseline, and 50.7% of patients showed 50% improvement in Eczema Area and Severity Index score.The efficacy of baricitinib was also reflected in the patient reported outcomes, with 55%–58% improvements in Patient-Oriented Eczema Measure, Atopic Dermatitis Control Tool, and Dermatology Life Quality Index scores seen within 2 weeks of treatment. No new safety signals were detected in this study. Conclusion Baricitinib treatment for 52 weeks in Korean patients with itch dominant AD confirmed long term effectiveness and safety.

Purpose: While MRI-based tumor regression grade (mrTRG) has shown promise in evaluating pathologic response to concurrent chemoradiotherapy (CCRT) in rectal cancer, its ability to predict pathologic complete response remains limited.This study aimed to enhance mrTRG’s diagnostic performance in predicting ypT0–1N0 status, a key factor in considering non-radical management after CCRT for locally advanced rectal cancer (LARC). Methods: This retrospective study included 430 patients with LARC who underwent radical resection following CCRT at a single referral hospital between April 2018 and September 2024. Multivariable logistic regression was used to identify predictive factors associated with achieving ypT0–1N0 status. The diagnostic performances of mrTRG1–2 alone and in combination with other factors were assessed by comparing sensitivity, specificity, positive-predictive value (PPV), negative-predictive value, and area under the curve (AUC). Results: Ninety-three patients (21.6%) achieved ypT0–1N0. In the multivariable analysis, fungating type, cT1–2, and mrTRG1–2 were independent predictors for ypT0–1N0. Integrating mrTRG with gross tumor type yielded the highest AUC of 0.689 among the combined models. For predicting ypT0–1N0, the combination of mrTRG and gross tumor type improved PPV (79.2% vs. 41.5% for mrTRG alone) while also demonstrating enhanced sensitivity compared with ycT0–1N0, the conventional MRI-based predictor (40.9% vs. 22.6%). Conclusion This study demonstrated that combining mrTRG and gross tumor type improved the PPV of mrTRG in predicting ypT0–1N0 after CCRT in LARC. Further studies are warranted to validate the role of gross tumor type in refining predictive systems for selecting candidates for non-radical treatment.

Purpose: Postoperative complications following gastric cancer surgery significantly impact patient outcomes, yet standardized definitions for these events have not been consistently applied across institutions in Korea. This study aimed to develop a consensus-based, standardized complication classification system specific to gastrectomy for gastric cancer as part of the Korean Quality Improvement Platform in Surgery (K-QIPS) initiative. Methods: As part of K-QIPS, a dedicated task force team (TFT) was formed with surgical experts from fourteen high-volume hospitals across Korea. The TFT conducted ten formal meetings to review existing literature and international guidelines, and incorporated findings from randomized controlled trials. The final complication list was developed through expert consensus and structured into a standardized framework. A Data Entry Manual was created to support consistent data collection by surgical clinical reviewers. Results: The TFT defined specific postoperative complications following gastrectomy for gastric cancer, including anastomotic leakage, duodenal stump leakage, pancreatic fistula, intra-abdominal and luminal bleeding, delayed gastric emptying, and internal hernia. Notably, internal hernia was described in standardized form for the first time. General complications were developed first and overlapped in part with the gastric cancer-specific list. The task force also produced a Data Entry Manual that provides practical instructions to ensure consistency and accuracy in complication reporting. Conclusion This nationwide consensus initiative established the first standardized complication classification system for gastric cancer surgery in Korea. The proposed definitions and data entry system are expected to improve complication reporting, enable multicenter research, support surgical quality benchmarking, and ultimately enhance patient outcomes.

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.