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 Purpose To compare the epidemiological and clinical features of the rare patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with age- and sex-matched controls in a nationwide cohort from South Korea. Methods: This observational cohort study analyzed newly diagnosed CADASIL patients aged at least 20 years and matched controls using data from the National Health Information Database for 2004–2022. The cumulative incidence of CADASIL was assessed by age and sex, and compared between regions. Neurologic and systemic diseases were compared between the CADASIL and control groups. Results: The study analyzed 816 CADASIL patients and 816 age- and sex-matched controls aged 56.8±15.2 years (mean±standard deviation), among whom 48.3% were male. The cumulative incidence of CADASIL was 1.86 per 100,000 people (95% confidence interval [CI]=1.85– 1.87 per 100,000), and peaked at 60–69 years of age. In terms of regional distribution, the incidence was highest for Jeju, at 39.67 per 100,000 (95% CI 37.84–41.49 per 100,000). Neurologic diseases were more frequent in CADASIL patients, including Alzheimer’s disease (33.1% vs.20.0%), vascular dementia (84.9% vs. 5.0%), epilepsy (34.6% vs. 15.9%), stroke (70.7% vs. 27.6%), parkinsonism (18.9% vs. 11.0%), and depression (60.8% vs. 44.9%). Systemic diseases such as diabetes mellitus (78.9% vs. 68.9%) were also more common in CADASIL patients, while cancer (27.9% vs. 38.7%) and myocardial infarction (10.0% vs. 13.6%) were less common than in controls. The onset ages of all diseases were lower in CADASIL patients. Conclusions This study has provided a precise nationwide estimate of the CADASIL incidence and its regional distribution in South Korea. CADASIL patients showed higher incidence rates and earlier onsets of diverse clinical manifestations.

Background: and Purpose Whole-exome sequencing (WES) is a valuable tool for identifying causative mutations in adult moyamoya disease (MMD), thereby advancing our understanding of the genetic mechanisms underlying this condition. Here, we conducted the first WESbased association study aimed at identifying genetic modifiers implicated in MMD. Methods: This WES study involved 160 patients with MMD and 189 controls from a multicenter hospital-based biobank, and evaluated combined annotation-dependent depletion (CADD) scores. Mutant-allele frequencies were compared in 369,121 individuals derived from the UK Biobank (UKB) WES. Mutant-allele risk scores (MARSs) were created based on WESidentified mutations. Gene-based association analyses and pooled analyses in East-Asian populations were further performed. Results: Fourteen mutations reached the genome-wide significance criterion (p<5×10-8 ), among which the p.R4810K mutation in the ring finger protein 213 gene (RNF213) showed the strongest significance (odds ratio=117.4, p=8.54×10-24 ). Notably, two mutations—p.G576S (alpha-glucosidase [GAA]) and p.D54N (charged multivesicular body protein 6 [CHMP6])— exhibited high CADD scores of 32 and 25, respectively, whereas the RNF213 p.R4810K mutation demonstrated a moderate deleteriousness score of 10.63. Fourteen mutations exhibited significant differences in allele frequencies between patients and UKB controlled data (p<1×10-8 ).The MARS9 model (incorporating nine missense mutations) showed better predictability for MMD (90.89%). The analysis of gene-based associations revealed four candidate genes: GAA, RNF213, CHMP6, and CARD14 (p=5×10-19 to 4×10-7 ). The subsequent pooled analyses validated four mutations in East Asian populations: p.V1195M, p.D1331G, p.S2334N, and p.R4810K (p<3×10-8 ). Conclusions This pioneering study has corroborated the significance of p.R4810K and identified several causative mutations predisposing patients to MMD, which helps to improve the understanding of its polygenetic nature.

Purpose: To report a case of primary orbital apocrine adenocarcinoma in a patient diagnosed with gastric adenocarcinoma.Case summary: A 43-year-old male patient diagnosed with gastric adenocarcinoma 3 months prior presented with a gradually enlarging mass in the lower medial aspect of the left eye for 1 year. At initial examination, his best-corrected visual acuity was 1.0 in both eyes and slit-lamp examination revealed no abnormalities. The left eye exhibited proptosis with restricted adduction, abduction, and depression. Orbital magnetic resonance imaging revealed an irregularly shaped mass measuring 56 × 46 × 38 mm in the left inferomedial orbit, invading the medial and inferior rectus muscles. Histopathological analysis of the orbital tumor revealed abundant eosinophilic cytoplasm. Immunohistochemical staining was positive for androgen receptor, and gross cystic disease fluid protein-15, both of which were negative in the gastric adenocarcinoma tissue. Additionally, the mucin phenotypes observed differed from those in the gastric cancer tissue. Based on these findings, the patient was diagnosed with primary orbital apocrine adenocarcinoma. Conclusions Primary orbital apocrine adenocarcinoma is an extremely rare malignant tumor. In patients with gastric cancer, malignant tumors in the orbit can arise as either primary neoplasms or metastatic lesions. Therefore, accurate diagnosis through immunohistochemical staining is essential to determine the appropriate treatment approach.

Purpose: Endoscopic submucosal dissection (ESD) has become a standard minimally invasive treatment for selected patients with early gastric cancer (EGC). This study presents the first nationwide survey of patients with EGC treated with ESD in 2023, conducted by the Korean College of Helicobacter and Upper Gastrointestinal Research. Materials and Methods: Data were retrospectively collected from participating referral centers across Korea using a standardized case report form covering patient characteristics, tumor features, procedural details, histopathological findings, and clinical outcomes.Descriptive and comparative analyses were conducted to summarize nationwide ESD practice patterns and outcomes. Results: Data from 5,460 ESD cases from 5,250 patients across 27 institutions were analyzed. The mean age was 67.4 years, with 74.1% males. Multiple synchronous lesions were identified in 3.7%. Most lesions were located in the lower third of the stomach (64.0%), and differentiated-type adenocarcinomas accounted for 87.8%. The en bloc and complete resection rates were 99.2% and 91.4%, respectively. Curative resection was achieved in 80.5%, whereas local non-curative resection (L-NCR) and surgical non-curative resection (S-NCR) were identified in 2.8% and 16.7%, respectively. Additional surgery was performed more frequently in patients with S-NCR than in those with L-NCR (59.3% vs. 24.7%). The bleeding and perforation rates were 3.6% and 0.9%, respectively, and were mostly managed conservatively or endoscopically. The median length of hospitalization was 4.0 days. Conclusions This first nationwide survey provides a comprehensive overview of the current practice of EGC treatment using ESD in Korea, demonstrating high technical success and safety, and establishing a baseline dataset for future longitudinal research.

Background/Aims: Patients with postural tachycardia syndrome (POTS) commonly experience gastrointestinal (GI) symptoms. We aim to assess the feasibility and preliminary efficacy data for DA-9701, a prokinetic agent targeting 5-hy-droxytryptamine 1A, 5-hydroxytryptamine 4, and dopamine D 2 receptors, in patients with POTS. Methods: In a randomized, double-blind, placebo-controlled, single-center crossover trial, patients with POTS were given either 30 mg of DA-9701 or a placebo 3 times daily for eight weeks in a 1:1 ratio. After a 4-week washout, patients received the alternate treatment for another 8 weeks. The primary endpoint focused on assessing the change in GI symptoms (total Nepean Dyspepsia Index-Korean version [NDI-K] symptom score) from baseline over the 8 week-treatment period. Endpoints were assessed in all enrolled and randomized patients (intention-to-treat), and in those who completed the trial (per-protocol analysis). Results: Between January 2022 and August 2023, 24 patients were randomized (n = 12 per group), with 3 discontinuing after randomization. DA-9701 did not significantly improve primary endpoints for total NDI-K symptom scores in either the intention-to-treat (least-squares means, –13.9 vs. –9.5, P = 0.326) or per-protocol analyses (–17.2 vs –12.0, P = 0.242).Notably, a trend toward improvement in specific GI symptoms, such as upper abdominal pain, was observed in both intention-to-treat (–0.6 vs 0.7; P = 0.066) and per-protocol analyses (–0.9 vs 0.6; P = 0.045). No serious adverse events were observed. Conclusion DA-9701 did not improve GI symptoms in this crossover trial; however, its potential effect on specific GI symptoms merits further investigation.

Background/Aims: Spinal cord injury (SCI) frequently impairs defecation, severely affecting the quality of life. This study examines compensatory neural remodeling after SCI, focusing on basal colonic contractility, neural responses to electrical field stimulation, and alterations in excitatory cholinergic and inhibitory nitrergic pathways. Methods: Female Sprague–Dawley rats underwent either sham surgery or T10 spinal cord transection and were categorized into 3 groups: sham, 1-week post-SCI (acute), and 4-week post-SCI (chronic). Colonic contractility was assessed in an organ bath using electrical field stimulation in the presence of a nitric oxide synthase inhibitor. Neural protein expression was analyzed by immunofluorescence and Western blotting. Results: SCI produced region- and time-dependent impairments in colonic contractility, with distinct alterations in the proximal circular and longitudinal muscles across acute and chronic phases. Neural excitability shifted dynamically, showing enhanced excitatory activity in the proximal longitudinal muscle at 1-week and the distal circular muscle at 4-week post-SCI. Protein analysis revealed increased neuronal nitric oxide synthase in the proximal colon, decreasedsoluble guanylyl cyclase in the distal colon, upregulated muscarinic M3 receptor in the proximal colon, and reduced vaso-active intestinal peptide receptor 1 in both proximal and distal regions. Conclusion SCI induces spatiotemporal remodeling of excitatory and inhibitory neural pathways, contributing to colonic dysmotility and revealing potential targets for therapeutic intervention.

Purpose: Skeletal muscle, accounting for approximately 40% of the total body mass, plays a critical role in movement, postural support, and metabolic homeostasis. Muscle mass is determined by the balance between protein synthesis and degradation, which is closely regulated by the mitochondrial function. Mitochondrial dysfunctions contribute to muscle loss by promoting oxidative stress and cellular damage. This study examined the effects of masutakeside I, a lignan glycoside derived from Styrax japonicus, on the mitochondrial function and muscle differentiation in C2C12 myoblasts. Methods: C2C12 myoblasts differentiated into myotubes in the presence of masutakeside I (0–10 ng/mL). Myogenic differentiation was assessed by myosin heavy chain (MHC) immunofluorescence, and multinucleated myotubes and relative diameters were quantified.The mitochondrial function was evaluated by measuring the mitochondrial reactive oxygen species (ROS), mitochondrial mass, and mitochondrial membrane potential using MitoSOX, MitoTracker Green, and JC-1 staining, respectively. Gene expression related to muscle differentiation, protein degradation, and the mitochondrial life cycle was analyzed using quantitative reverse transcription polymerase chain reaction. Results: Masutakeside I significantly increased the number of multinucleated (≥ 5 nuclei) MHC-positive myotubes and relative myotube diameter compared to the control. In addition, masutakeside I upregulated the myogenic markers, including phosphoinositide 3-kinase and MHC isoforms (Myh2, Myh4, and Myh7), while significantly downregulating protein degradation–related genes, including mothers against decapentaplegic homolog 2/3, forkhead box protein O1, atrogin-1, and muscle RING finger-1. Masutakeside I modulated the mRNA expression of the mitochondrial function and mitophagy-related markers, suggesting its potential involvement in mitochondrial quality control. Consistent with these effects, the mitochondrial ROS levels decreased, whereas mitochondrial mass and membrane potential increased. Conclusion These findings suggest that masutakeside I modulates the markers related to myogenic differentiation, muscle protein degradation, and mitochondrial function.

Drug-induced phospholipidosis (DIP) is characterized by intracellular accumulation of phospholipids with lamellar body formation secondary to drug-altered lipid metabolism, which can trigger inflammation and histopathological changes. Fabry disease and DIP both exhibit zebra bodies on electron microscopy, complicating differential diagnosis. A 17-year-old male with microscopic hematuria and proteinuria had received atomoxetine (40 mg) for 11 months to treat attention-deficit hyperactivity disorder. Light microscopy showed one glomerulus with perihilar sclerosis and periglomerular fibrosis. Kidney biopsy revealed zebra bodies in podocytes, initially suggesting Fabry disease. However, α-galactosidase A enzyme activity was normal on tandem mass spectrometry. Next-generation sequencing of GLA identified only three benign variants. This represents the first reported case of atomoxetine-induced DIP. When zebra bodies are observed, clinicians should consider DIP caused by cationic amphiphilic drugs alongside Fabry disease. Atomoxetine meets the structural criteria for inducing DIP, and awareness of this potential complication is essential.