Objective: Lipopolysaccharide (LPS), derived from various infectious bacteria in the uterus, interferes with communication between embryonic trophoblasts and endometrial cells, thereby inhibiting successful embryo implantation. This study aimed to investigate the effects of LPS and the anti-inflammatory compound nicotinamide (NAM) on early embryo implantation processes, focusing on the adhesion and outgrowth between trophoblast spheroids and endometrial cells. Methods: We used JAr mixed JEG-3 (JmJ) spheroids, prepared by combining JAr and JEG-3 cells in a 1:1 ratio. Following treatment with LPS with or without NAM, the attachment and outgrowth of JmJ spheroids on endometrial epithelial cells (ECC-1) were assessed. Additionally, changes in the gene expression of inflammatory cytokines (chemokine (C-X-C motif) ligand 1 [CXCL1], interleukin 8 [IL-8], and IL-33) and cell adhesion molecules (integrin alpha-V [ITGαV], integrin beta 3 [ITGβ3], and integrin beta 5 [ITGβ5]) in ECC-1 cells following LPS and/or NAM treatment were evaluated using quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blot analysis. Results: Decreased attachment rates and reduced outgrowth areas caused by LPS treatment were significantly restored by NAM. These restorative effects of NAM were associated with the modulation of inflammatory cytokines—specifically CXCL1 and IL-33, as shown by qRT-PCR—and expression of the cell adhesion molecule ITGβ3, as indicated by Western blot analysis. Conclusion Our study confirmed that LPS-induced endometrial infection may inhibit embryo implantation. NAM treatment ameliorated the detrimental effects of LPS by modulating the expression of inflammatory cytokines and adhesion molecules. Further studies are needed to explore the potential use of NAM as an effective additive to improve embryo implantation rates in human in vitro fertilization-embryo transfer programs.

Secondary rhabdoid tumors (RTs) with atypical teratoid/rhabdoid tumor-like features rarely arise from, or coexist with, pleomorphic xanthoastrocytomas (PXAs), and their clinicopathological and molecular characteristics remain poorly understood. We report a 17-year-old girl with a temporal lobe mass that, upon gross total resection, pathologically contained both RT and PXA components. Immunohistochemistry revealed loss of INI1 expression restricted to the RT component, while the PXA area retained INI1. Next-generation sequencing identified a shared BRAF::TRIM24 fusion and homozygous deletion of CDKN2A/2B in both components, indicating a shared clonal origin. Additionally, a germline ATM frameshift mutation (c.5288_5289insGA) was identified in both tumor components, making the first such report in central nervous system tumors. SMARCB1 loss was confined to the RT component, further supporting the hypotheses of clonal evolution and secondary transformation. Despite gross total resection, craniospinal irradiation, and chemotherapy, the patient developed rapid leptomeningeal dissemination and died 5 months after surgery. This case provides clinicopathological and molecular evidence for clonal evolution and secondary transformation of PXA into an RT. The presence of germline ATM mutation may have therapeutic and biological relevance. Further studies are required to clarify the pathogenesis and optimal management of these rare and aggressive tumors.

Background: The conventional magnetic resonance imaging (MRI) grading system for foraminal stenosis (FS), known as the Lee classification, was introduced in 2010 and is widely utilized in clinical practice. Previous studies have reported that the conventional grading system for FS lacks prediction ability for surgical treatment. The purpose of this study was to develop a novel MRI grading system for lumbar FS with improved prediction ability for surgical treatment by incorporating facet effusion to indicate segmental instability. Methods: We retrospectively reviewed patients diagnosed with lumbar FS between 2011 and 2017 who had a follow-up period of at least 5 years. The FS severity was assessed using a conventional MRI grading system developed by Lee et al. We recorded whether the patient underwent surgical treatment for FS during the follow-up period and the time from the initial diagnosis to surgery. Survival analysis using a Kaplan-Meier curve and log-rank test was performed to verify the impact of FS severity on the surgical treatment. We performed additional survival analysis after modifying the grading system by incorporating the presence of excessive facet joint effusion assessed using axial MRI. We also compared the discrimination ability of the modified and conventional grading systems using Uno’s concordance index (C-index). Results: In total, 235 patients with a mean age of 63.7 years were included in this study. During the mean follow-up period of 8.1 years, 63 patients underwent surgical treatment for FS. The conventional grading system revealed no significant difference in survival between the grade 2 and 3 groups (p = 0.104). Conversely, the modified grading system revealed a significant difference in survival between the new grade 2 and 3 groups (p < 0.001). After modification, the discrimination ability, assessed using Uno’s Cindex, significantly improved from 0.69 to 0.73. Conclusions The Facet Effusion-Incorporating Grading System, which adds excessive facet joint effusion to the conventional MRI grading framework, demonstrated improved predictive value for surgical treatment and better discriminatory ability compared with the original system.

Background: and Purpose: Clinicians typically use 2 methods to determine impairment in a specific cognitive domain based on the Seoul Neuropsychological Screening Battery, 2nd Edition: (1) identifying impairment when one or more subtests fall below the normal range (< mean −1.5 standard deviation), and (2) using the cognitive domain score. Because agreement between these methods may differ by the severity of cognitive impairment, this study examined their concordance in the overall sample and across Clinical Dementia Rating (CDR) levels. Methods: A total of 1,086 patients (age 74.27±9.62 years; education 9.07±4.77 years) were included. Concordance between subtest-based and domain score-based classifications was assessed for each cognitive domain using cross-tabulation analyses and Cohen’s kappa statistics. To assess the influence of the severity of cognitive impairment, analyses were conducted across CDR levels. Results: When impairment was defined as having at least one abnormal subtest, concordance rates were 90.8% for Attention, 88.8% for Language, 84.6% for Visuospatial Function, 74.3% for Memory, and 73.6% for Frontal/Executive Function. In the Frontal/ Executive Function domain, requiring 2 or more abnormal subtests increased concordance to 90.9%. CDR subgroup analyses showed that Memory concordance was particularly low in the CDR 0.5 group (65.8%) compared with the CDR 1 (85.5%) and CDR 2 (98.5%) groups. Conclusions Concordance between the 2 classification methods was moderately high for Attention, Language, and Visuospatial Function but substantially lower for Memory and Frontal/Executive Function, especially in individuals with mild cognitive impairment. These findings highlight the need to consider both subtest-level performance and domain scores when determining impairment in memory or frontal/executive function.

Background/Aims: Recent advances in computer-aided diagnosis (CADx) systems have demonstrated expert-level accuracy in the optical diagnosis of colorectal polyps. High-confidence (HC) diagnoses have been defined as those made within 3 seconds without hesitation, and these systems have been shown to improve diagnostic accuracy. We aimed to evaluate the performance of endoscopists with varying levels of experience in diagnosing colorectal polyps with the assistance of a new CADx system applying the 3-second rule and without artificial intelligence assistance. Methods: In this multicenter ex vivo study, 35 endoscopists assessed 100 polyps (51 adenomas, 39 hyperplastic polyps, 10 sessile serrated lesions) using narrow-band imaging video clips on an online platform. Assessments consisted of individual endoscopist diagnosis and CADx-assisted diagnosis. HC assignments followed the 3-second rule in both phases. Performance metrics included HC accuracy, HC rate, and adherence to the Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) and Simple Optical Diagnosis Accuracy (SODA) thresholds. Results: HC diagnostic accuracy improved from 78.3% (95% confidence interval [CI], 76.6% to 80.0%) to 89.8% (95% CI, 88.6% to 90.9%) with CADx assistance (p<0.001). The proportion of HC predictions increased from 64.2% to 75.4% (p<0.001). Novice endoscopists showed marked improvement with CADx (74.1% vs 88.8%; p<0.001). CADx-assisted diagnoses nearly met SODA and PIVI thresholds under the 3-second rule. Additional analysis demonstrated that CADx assistance significantly improved interobserver agreement and ground truth, particularly for novices (κ=0.37 to κ=0.65; p<0.001). Conclusions Integrating CADx with the 3-second rule significantly enhances the performance of endoscopists in the optical diagnosis of colorectal polyps, with the greatest benefit observed among novice endoscopists.

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 assess long-term outcomes of vesicostomy on bladder capacity (BC) and voiding function in non-neurogenic bladder, and explore the association between kidney ultrasonographic findings and renal function. Materials and Methods: Thirty-four patients under 2 years at the time of vesicostomy formation (2005–2020) with ≥3 years of follow-up were reviewed. Patients were further stratified based on neurogenic bladder status. Twenty-one patients were nonneurogenic. A subgroup analysis of 7 patients under 3 months with primary vesicoureteral reflux (VUR) and compromised renal function was conducted. Results: The median age at vesicostomy formation was 1.0 months (interquartile range [IQR] 0.0–3.5); the median duration of vesicostomy was 16.0 months (IQR 8.0–21.0). At a median age of 93.0 months (IQR 59.5–117.5), all patients achieved spontaneous micturition and continence. Eleven patients (52.4%) showed bell-shaped voiding patterns. Five patients showed interrupted (n=2) or plateau (n=3) patterns. With the exemption one patient, all patients with primary VUR showed bell-shaped curves. None initiated clean intermittent catheterization during follow-up. The median BC-to-estimated BC in patients with non-neurogenic bladder and primary VUR was 0.9 (IQR 0.7–1.1) and 0.9 (IQR 0.8–1.1), respectively. Three patients underwent revision due to prolapse. The glomerular filtration rate (GFR) was improved by 68.9% compared to the baseline (p=0.045). Parenchymal abnormalities on kidney ultrasonography were associated with decrease in GFR. Conclusions Vesicostomy in non-neurogenic bladder patients was associated with recovery of BC, preservation of continence, and improved renal function. Parenchymal abnormalities on ultrasonography predicted lower GFR.

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.

Hypersensitivity reactions (HSRs) to iodinated contrast media (ICM) can range from mild cutaneous symptoms to life-threatening anaphylaxis. In patients with a history of ICM hypersensitivity, avoidance of the culprit agent is generally recommended. This case report describes a successful desensitization in a 56-year-old man with recurrent HSRs to multiple agents including ioversol, iohexol, iobitridol, and iopamidol. Intradermal testing was performed to identify potentially safe alternatives; however, all tested agents, including iohexol, ioversol, iobitridol, iopamidol, iodixanol, iomeprol, and iopromide, yielded positive results. Given the clinical necessity of transcatheter arterial chemoembolization, a 13-step rapid desensitization protocol with iodixanol was implemented. The procedure was completed without any breakthrough reactions. This case highlights desensitization as a feasible and effective strategy for patients with hypersensitivity to multiple ICM agents.