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 Criteria for amyloid-related imaging abnormalities in anti-amyloid therapy are based on T2* gradient-recalled echo (GRE), but susceptibility-weighted imaging (SWI) is widely used, creating uncertainty. This study quantitatively compared the detectability of SWI and GRE for cerebral microbleeds and established evidence supporting distinct microbleed criteria for each. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed and Embase were searched for studies directly comparing SWI and GRE up to August 8, 2024. Study quality was assessed with QUADAS-2. The pooled proportion of microbleed detection and detection ratio were calculated. Subgroup analyses were performed based on magnetic field strength (1.5 T vs. 3 T) and SWI slice thickness (<2 mm vs. ≥2 mm), equipment vendor, and study quality. Results: Thirteen studies were included. SWI detected cerebral microbleeds approximately 1.6times more effectively than GRE. At 3.0 T and 1.5 T, SWI exhibited 1.7-fold and 1.5-fold greater detectability, respectively. SWI with thinner slices (<2 mm) showed a 1.9-fold improvement, while thicker slices (≥2 mm) showed a 1.3-fold improvement. Subgroup analyses revealed no significant differences between vendors (0.61 vs. 0.60, p=0.89), or by study quality (0.61 vs. 0.59,p=0.89). Conclusions SWI detects cerebral microbleeds about 1.6 times more effectively than GRE, highlighting important differences between the two techniques. Cautious exploration of adjusted thresholds may be needed, and prospective validation in therapy-specific cohorts will be essential before clinical application.

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: 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.

Endoscopic surgery has emerged as a viable treatment option for cervical stenotic myelopathy, offering several advantages over conventional approaches. In multilevel cervical myelopathy, traditional microscopic laminoplasty via the posterior approach requires muscle dissection along the spinous process, which serves as the insertion point for stabilizing muscles, thereby disrupting the posterior tension band. Recently, endoscopic laminoplasty techniques have been explored; however, these often involve detaching the spinous tip from the lamina, compromising the cervical fulcrum. In this report, we introduce a novel surgical technique using a unilateral biportal endoscopy (UBE) system that preserves key cervical structures typically damaged by prior open or endoscopic laminoplasty methods. An 82-year-old man presented with bilateral lower-extremity weakness. Imaging revealed stenosis at C3–4–5 with associated cord signal changes. Maintain anatomy laminoplasty was performed using the UBE system, preserving both the posterior tension band and the spinous process fulcrum. Postoperatively, the modified Japanese Orthopaedic Association and Numeric Rating Scale scores improved. The patient was discharged on postoperative day 4. This new unilateral biportal endoscopic cervical laminoplasty is a safe, effective, and minimally invasive technique that achieves complete decompression in multilevel cervical stenotic myelopathy while maintaining critical anatomical structures.

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.

Purpose: Atherosclerotic plaques in peripheral arterial disease (PAD) include fatty, mixed, and calcified types. Plaque burden is significantly associated with restenosis, reintervention, and amputation-free survival. Rotational and aspirational atherectomy (RAA) may effectively remove such plaques. This study aimed to evaluate long-term outcomes of RAA for infrainguinal PAD. Methods: Patients with infrainguinal lesions underwent revascularization using the Jetstream Atherectomy System (Boston Scientific). This 60-month extension assessed primary patency rate (PPR) and clinically driven target lesion revascularization (CD-TLR). Kaplan-Meier curves were used for survival analysis; P < 0.05 was considered statistically significant. Results: A total of 150 patients (mean age, 70.9 years; male, 86.0%; 65.4% with diabetes) were enrolled. The mean lesion length was 15.8 cm, with 74.0% occlusions and 47.3% severe calcification. Lesions were sclerotic (72.4%), thrombosclerotic (13.4%), thrombotic (9.4%), or in-stent (4.7%). A drug-coated balloon (DCB) was used in 85.5% of cases. PPR at 1, 3, and 5 years was 84.1%, 68.1%, and 58.5%, respectively. CD-TLR rates were 93.0%, 81.5%, and 67.4%, respectively. The benefit of DCB was sustained through 3 years but attenuated thereafter, highlighting the need for extended follow-up in infrainguinal interventions. Conclusion RAA demonstrated durable 5-year patency and safety outcomes. Device type, DCB use, lesion morphology, and calcium grade did not significantly influence long-term results. Lesion complexity remains the primary predictor of clinical outcome. Despite the complexity of infrainguinal lesions, the use of RAA demonstrated sustained patency through 3 years, with lesion complexity (particularly TASC classification) emerging as the most critical predictor of long-term success.

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.

Purpose: Metabolic bariatric surgery (MBS) efficacy and safety is established for older patients, but East Asian data are limited. This study aimed to evaluate the safety and efficacy of MBS by comparing older (≥55 years) and younger (<55 years) East Asian patients with obesity. Methods: This multicenter, retrospective review included 410 patients undergoing MBS from January to December 2019.Patients were stratified into the older group (OG, age ≥55 years; n = 39) and the younger group (YG, age <55 years; n = 371). We compared surgical safety, weight parameters, and comorbidity resolution rates. Results: The OG had lower mean body weight (97.9 ± 16.4 kg vs. 113.2 ± 23.1 kg, P < 0.001) but more comorbidities and lower average ABCD score for type 2 diabetes mellitus (T2DM) remission. Postoperative complication rate (12.8% vs. 7.5%, P = 0.400) and postoperative hospital stay (4.1 ± 1.8 days vs. 4.0 ± 8.9 days, P = 0.773) showed no significant differences.At 12 months, the percentage of total weight loss was significantly lower in the OG (23.7 ± 6.9% vs. 27.8 ± 8.4%, P = 0.014).Remission rates for T2DM (47.6% vs. 80.5%, P < 0.001), hypertension (34.6% vs. 57.5%, P = 0.073), and dyslipidemia (12.5% vs. 44.4%, P = 0.012) were also lower in the OG, yet still demonstrated clinically meaningful metabolic improvement. Conclusion MBS is a safe and effective treatment for older East Asians with obesity, offering substantial comorbidity resolution despite achieving a lower weight loss compared to the younger patients.

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.