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.

Purpose: To develop and validate an artificial intelligence (AI)-based personalized outcome prediction model for upper-urinary tract urothelial carcinoma patients undergoing radical nephroureterectomy. Materials and Methods: Data from patients who underwent radical nephroureterectomy between 2010 and 2020 across three hospitals were retrospectively analyzed. A model was developed using one tertiary center’s data and externally validated with data from two other hospitals. An AI model using XGBoost as risk estimator and bootstrapped Weibull Accelerated Failure Time model for 10-year survival probability was employed. Hyperparameter tuning used Optuna method. Model efficacy was assessed using concordance index, average Brier score, D-calibration, and six-month interval time-dependent area under the curve (AUC). Results: Of 1,039 patients, 627 qualified after excluding 50 with neoadjuvant chemotherapy. Model development used 564 patients (507 training, 57 test) with 9:1 stratified random split, plus 63 for internal validation and 362 for external validation. Significant parameters included preoperative glomerular filtration rate (p<0.001), hydroureteronephrosis (p=0.013), pathological N stage (p<0.001), concurrent carcinoma in situ (p<0.001), disease progression (p<0.001), and survival rate (p<0.001). Disease-free survival (DFS) model’s concordance index: internal validation 0.789, external validations 0.734 and 0.771. Overall survival (OS) model’s concordance index: internal validation 0.819, external validations 0.780 and 0.771. Mean time-dependent AUC was 0.66–0.77 for DFS and 0.67–0.80 for OS during 10-year periods. Conclusions AI-based model effectively predicts disease-free and OS outcomes for upper-urinary tract urothelial carcinoma patients with post-radical nephroureterectomy, showcasing robust performance across multicenter settings.

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.

Background: s/Aims: Pancreaticoduodenectomy (PD) is the standard treatment for periampullary tumors, but it is technically challenging. Evidence directly comparing open, laparoscopic, robotic, and hybrid approaches is limited. This study conducts a network meta-analysis (NMA) to compare the perioperative and oncologic outcomes of open PD (OPD), laparoscopic PD (LPD), robotic PD (RPD), and hybrid PD. Methods: We searched PubMed, EMBASE, and the Cochrane Library for studies published between January 1994 and August 2024.We included randomized controlled trials and comparative observational studies that evaluated at least two PD approaches. Perioperative outcomes were the primary endpoints, while oncologic safety served as a secondary endpoint. A random-effects NMA was performed, establishing treatment hierarchies through ranking probabilities (PROSPERO ID: CRD420250365864). Results: A total of 78 studies were included (5 randomized and 73 retrospective). RPD was associated with lower blood loss compared to OPD (mean difference [MD], –163.85 mL) and LPD (MD, –84.14 mL). Hospital stays were also shorter for RPD compared to OPD (MD, –2.50 days) and LPD (MD, –1.88 days). In contrast, OPD was the most time-efficient approach compared to LPD (MD, –77.61 minutes) and RPD (MD, –73.30 minutes). Mortality rates, severe complications, clinically relevant postoperative pancreatic fistula rates, and reoperation rates were comparable across all surgical approaches. In terms of oncologic safety, lymph node yield and R0 resection rates were similar for all modalities. Conclusions While OPD is the most time-efficient approach, RPD provides significant advantages in reducing intraoperative blood loss and shortening hospital stays compared to both LPD and OPD.

Background: Transthyretin amyloidosis, a protein-misfolding disorder characterized by systemic amyloid deposition, can be classified as wild-type transthyretin amyloidosis (ATTRwt) or hereditary transthyretin amyloidosis (ATTRv), depending on the presence of transthyretin (TTR) gene variants. We examined the genetic distribution of TTR variants in Korean patients diagnosed with ATTRv. Methods: We retrospectively reviewed 801 participants who underwent TTR analysis at Samsung Medical Center from 2012 to 2024. The participants were categorized into two groups: in-house probands or relatives, and externally referred probands or relatives. Results: Pathogenic or likely pathogenic TTR variants were detected in 36 of 165 in-house probands (21.8%), among which D38A was the most frequent variant (50.0%; 18/36), followed by M13dup and E89K (8.3% each). Among referred probands, D38A was predominant (54.5%; 12/22), followed by M13dup (22.7%; 5/22). Cardiac amyloid involvement was the most common manifestation, observed in 97.2% (35/36) of in-house probands with ATTRv, followed by peripheral nervous system (PNS; 94.4%) and autonomic nervous system (ANS; 88.9%) involvement. In contrast, ANS involvement was most prevalent among in-house relatives who underwent organ evaluation (61.5%; 24/39), followed by cardiac (52.1%; 25/48) and PNS (48.7%; 19/39) involvement. Five of the eight in-house relatives harboring M13dup (62.5%) showed organ involvement, primarily in the ANS, supporting the pathogenicity of this variant. Conclusions This study provides the largest single-institution dataset of Korean patients with ATTRv, incorporating systematic organ assessments. The predominance of the unique TTR variants D38A and M13dup delineates a distinct genetic landscape that may facilitate accurate and timely diagnosis of ATTRv in the Korean population.

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.

Myopia, particularly high myopia, is a significant risk factor for several ocular pathologies including cataract, glaucoma, and retinal detachment. Excessive axial elongation associated with high myopia can induce biomechanical stretching, increasing the risk of serious complications like posterior staphyloma and myopic maculopathy. Global meta-analyses estimate that approximately 10 million people were visually impaired due to myopic maculopathy in 2015, with 3 million being blind. Recent nationwide surveys in South Korea revealed a prevalence of 65.4% for myopia and 6.9% for high myopia in children and adolescents, highlighting the urgent need for effective management. Delaying the onset and slowing the progression of myopia during childhood and adolescence is crucial for reducing the potential lifetime risk of these complications. This consensus statement, prepared by the Korean Myopia Society for the Korean Association for Pediatric Ophthalmology and Strabismus (KAPOS), reviews the current evidence for myopia control interventions and provides management strategies applicable to the South Korean clinical setting. Key interventions covered include lifestyle modifications (outdoor time, near work adjustment), optical methods (myopia-control spectacle lenses, dual-focus soft contact lenses, orthokeratology), and pharmacologic treatment (low-concentration atropine), as well as combination therapies. The statement also addresses patient selection, treatment outcome evaluation using spherical equivalent and axial length changes, and the crucial aspects related to treatment cessation and the rebound effect.

Objective: This study aimed to evaluate the feasibility, safety, and oncologic outcomes of irreversible electroporation (IRE) using a clustered electrode in patients with locally advanced pancreatic cancer (LAPC). Materials and Methods: In this single-center prospective cohort study, 13 patients with LAPC (median age, 60 years; range, 48–78 years) underwent clustered electrode IRE between September 2022 and September 2024. Patient characteristics, procedural details, and clinical outcomes were recorded. Endpoints included technical success, procedure-related complications, overall survival (OS), and progression-free survival (PFS). Results: Tumors were located in the pancreatic head in four patients (30.8%) and in the body/tail in nine (69.2%). The median tumor size was 2.4 cm (1.5–4.0 cm), and vascular invasion was present in all patients. Technical success was achieved in all patients. Intraoperative IRE was performed in 11 (84.6%) patients, and 2 (15.4%) patients underwent percutaneous IRE. Gastrointestinal bleeding events as major complications occurred in two patients (15.4%) and, both were successfully controlled by embolization. No 60-day mortality was observed. At a median follow-up of 24.5 months (range, 9.9–33.4 months) after IRE, median OS and PFS from IRE were 20.1 and 14.5 months, respectively. Conclusion IRE using clustered electrodes for LAPC appears to be a feasible therapeutic approach, offering reliable technical success and acceptable safety. Survival outcomes are encouraging; however, larger, controlled studies are required.

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.

Purpose: Neoadjuvant treatment (NAT) is now the standard for borderline resectable pancreatic cancer (RPC) and is being considered for RPC. Early recurrence after curative surgery in RPC is often seen as a treatment failure, prompting considerations for NAT. Our goal was to develop an artificial intelligence (AI)-based predictive model utilizing preoperatively available factors to forecast early recurrences of resected RPC. Methods: This study included 469 patients who underwent surgery for RPC between 2011 and 2019. Clinicopathologic and oncologic data were retrospectively reviewed. Preoperative variables, including laboratory data and imaging findings, were collected. Early recurrence was defined as recurrence occurring within a year after surgery. Deep neural networks were then used to select variables by assessing their importance. A new model predicting early recurrence of RPC was subsequently developed. Results: Of the patients evaluated, 199 (42.4%) experienced early recurrence. The predictive model included 14 preoperative variables: CA 19-9, preoperative pancreatitis, serum albumin, platelet count, lymphocyte count, the American Society of Anesthesiologists physical status classification, tumor size, monocyte count, age, body mass index, CRP, hemoglobin, WBC count, and CEA. The area under the curve for the model was 0.786 in the training set and 0.734 in the test set. Conclusion We developed an AI-based model to predict the early recurrence of RPC using preoperative parameters. By identifying patients at risk of early recurrence, optimal individualized treatments such as NAT can be considered. Future prospective studies are crucial to establish clear indications for NAT in RPC.