Cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) is a neurodegenerative disorder caused by a biallelic expansion of pentanucleotide repeats in the RFC1 gene. Previous studies have reported up to 22% of patients with late-onset ataxia harbor this pathogenic repeat expansion. Despite its relatively high prevalence, CANVAS is often underdiagnosed because the disease is not well recognized and genetic testing is not performed in clinical practice. Here, we present a patient with characteristic clinical features, confirmed by genetic testing.

Background: and Purpose This study evaluated the diagnostic utility of an anti-signal-recognition particle 54 (anti-SRP54) antibody-based enzyme-linked immunosorbent assay (ELISA) as well as the clinical, serological, and pathological characteristics of patients with SRP immune-mediated necrotizing myopathy (IMNM). Methods: We evaluated 87 patients with idiopathic inflammatory myopathy and 107 healthy participants between January 2002 and December 2023. The sensitivity and specificity of the ELISA for anti-SRP54 antibodies were assessed, and the clinical profiles of patients with antiSRP54 antibodies were determined. Results: The ELISA for anti-SRP54 antibodies had a sensitivity and specificity of 88% and 99%, respectively, along with a test–retest reliability of 0.92 (p<0.001). The 32 patients diagnosed with anti-SRP IMNM using a line-blot immunoassay included 28 (88%) who tested positive for anti-SRP54 antibodies using the ELISA, comprising 12 (43%) males and 16 (57%) females whose median ages at symptom onset and diagnosis were 43.0 years and 43.5 years, respectively. Symptoms included proximal muscle weakness in all 28 (100%) patients, neck weakness in 9 (32%), myalgia in 15 (54%), dysphagia in 5 (18%), dyspnea in 4 (14%), dysarthria in 2 (7%), interstitial lung disease in 2 (7%), and myocarditis in 2 (7%). The median serum creatine kinase (CK) level was 7,261 U/L (interquartile range: 5,086–10,007 U/L), and the median anti-SRP54 antibody level was 2.0 U/mL (interquartile range: 1.0–5.6 U/mL). The serum CK level was significantly higher in patients with coexisting anti-Ro-52 antibodies. Conclusions This study has confirmed the reliability of the ELISA for anti-SRP54 antibodies and provided insights into the clinical, serological, and pathological characteristics of South Korean patients with anti-SRP IMNM.

Background: and Purpose Treatments for neuromyelitis optica spectrum disorder (NMOSD) such as eculizumab, ravulizumab, satralizumab, and inebilizumab have significantly advanced relapse prevention, but they remain expensive. Rituximab is an off-label yet popular alternative that offers a cost-effective solution, but its real-world efficacy needs better quantification for guiding the application of newer approved NMOSD treatments (ANTs). This study aimed to determine real-world rituximab failure rates to anticipate the demand for ANTs and aid in resource allocation. Methods: We conducted a nationwide retrospective study involving 605 aquaporin-4-antibody-positive NMOSD patients from 22 centers in South Korea that assessed the efficacy and safety of rituximab over a median follow-up of 47 months. Results: The 605 patients treated with rituximab included 525 (87%) who received continuous therapy throughout the follow-up period (median=47 months, interquartile range=15–87 months). During this period, 117 patients (19%) experienced at least 1 relapse. Notably, 68 of these patients (11% of the total cohort) experienced multiple relapses or at least 1 severe relapse.Additionally, 2% of the patients discontinued rituximab due to adverse events, which included severe infusion reactions, neutropenia, and infections. Conclusions This study has confirmed the efficacy of rituximab in treating NMOSD, as evidenced by an 87% continuation rate among patients over a 4-year follow-up period. Nevertheless, the occurrence of at least one relapse in 19% of the cohort, including 11% who experienced multiple or severe relapses, and a 2% discontinuation rate due to adverse events highlight the urgent need for alternative therapeutic options.

Gastric cancer is one of the most common cancers in both Korea and worldwide. Since 2004, the Korean Practice Guidelines for Gastric Cancer have been regularly updated, with the 4th edition published in 2022. The 4th edition was the result of a collaborative work by an interdisciplinary team, including experts in gastric surgery, gastroenterology, endoscopy, medical oncology, abdominal radiology, pathology, nuclear medicine, radiation oncology, and guideline development methodology. The current guideline is the 5th version, an updated version of the 4th edition. In this guideline, 6 key questions (KQs) were updated or proposed after a collaborative review by the working group, and 7 statements were developed, or revised, or discussed based on a systematic review using the MEDLINE, Embase, Cochrane Library, and KoreaMed database. Over the past 2 years, there have been significant changes in systemic treatment, leading to major updates and revisions focused on this area.Additionally, minor modifications have been made in other sections, incorporating recent research findings. The level of evidence and grading of recommendations were categorized according to the Grading of Recommendations, Assessment, Development and Evaluation system. Key factors for recommendation included the level of evidence, benefit, harm, and clinical applicability. The working group reviewed and discussed the recommendations to reach a consensus. The structure of this guideline remains similar to the 2022 version.Earlier sections cover general considerations, such as screening, diagnosis, and staging of endoscopy, pathology, radiology, and nuclear medicine. In the latter sections, statements are provided for each KQ based on clinical evidence, with flowcharts supporting these statements through meta-analysis and references. This multidisciplinary, evidence-based gastric cancer guideline aims to support clinicians in providing optimal care for gastric cancer patients.

Objective: In South Korea, there is a significant gap in systematic, evidence-based research on intensive case management (ICM) for individuals with severe mental illness (SMI). This study aims to evaluate the effectiveness of ICM through a randomized controlled trial (RCT) comparing ICM with standard case management (non-ICM). Methods: An RCT was conducted to assess the effectiveness of Seoul-intensive case management (S-ICM) vs. non-ICM in individuals with SMI in Seoul. A total of 78 participants were randomly assigned to either the S-ICM group (n=41) or the control group (n=37). Various clinical assessments, including the Brief Psychiatric Rating Scale (BPRS), Montgomery–Åsberg Depression Rating Scale, Health of the Nation Outcome Scale, and Clinical Global Impression-Improvement (CGI-I), along with quality-of-life measures such as the WHO Disability Assessment Schedule, WHO Quality of Life scale, and Multidimensional Scale of Perceived Social Support (MSPSS) were evaluated over a 3-month period. Statistical analyses, including analysis of covariance and logistic regression, were used to determine the effectiveness of S-ICM. Results: The S-ICM group had significantly lower odds of self-harm or suicidal attempts compared to the control group (adjusted odds ratio [aOR]=0.30, 95% confidence interval [CI]: 0.21–1.38). Psychiatric symptoms measured by the BPRS and perceived social support measured by the MSPSS significantly improved in the S-ICM group. The S-ICM group also had significantly higher odds of CGI-I compared to the control group (aOR=8.20, 95% CI: 2.66–25.32). Conclusion This study provides inaugural evidence on the effectiveness of S-ICM services, supporting their standardization and potential nationwide expansion.

Background: Kelch-like ECH-associated protein 1 (KEAP1)–nuclear factor erythroid- 2-related factor 2 (NRF2) pathway is a major regulator protecting cells from oxidative and metabolic stress. Studies have revealed that this pathway is involved in mediating resistance to cytotoxic chemotherapy and immunotherapy; however, its implications in oncogene-addicted tumors are largely unknown. This study aimed to elucidate whether this pathway could be a potential therapeutic target for epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Methods: We measured the baseline expression of NRF2 using EGFR-mutant parental cells and acquired gefitinib resistant cells. We investigated whether NRF2 inhibition affected cell death in vitro and tumor growth in vivo using a xenograft mouse model, and compared the transcriptional changes before and after NRF2 inhibition. Results: Baseline NRF2 expression was enhanced in PC9 and PC9 with gefitinib resistance (PC9/GR) cells than in other cell lines, with a more prominent expression in PC9/ GR. The NRF2 inhibitor induced NRF2 downregulation and cell death in a dose-dependent manner. Cotreatment with an NRF2 inhibitor enhanced osimertinib-induced cell death in vitro, and potentiated tumor growth inhibition in a PC9/GR xenograft model. Finally, RNA sequencing revealed that NRF2 inhibition resulted in the altered expression of multiple genes involved in various signaling pathways. Conclusion We identified that NRF2 inhibition enhanced cell death and inhibited tumor growth in tyrosine kinase inhibitor (TKI)-resistant lung cancer with EGFR-mutation. Thus, NRF2 modulation may be a novel therapeutic strategy to overcome the resistance to EGFR-TKIs.

Purpose: Recent development in perioperative treatment of resectable non–small cell lung cancer (NSCLC) have changed the landscape of early lung cancer management. The ADAURA trial has demonstrated the efficacy of adjuvant osimertinib treatment in resectable NSCLC patients; however, studies are required to show which subgroup of patients are at a high risk of relapse and require adjuvant epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment. This study evaluated risk factors for postoperative relapse among patients who underwent complete resection. Materials and Methods: Data were obtained from the Korean Association for Lung Cancer Registry (KALC-R), a database created using a retrospective sampling survey by the Korean Central Cancer Registry (KCCR) and the Lung Cancer Registration Committee. Results: A total of 3,176 patients who underwent curative resection was evaluated. The mean observation time was approximately 35.4 months. Among stage I to IIIA NSCLC patients, the EGFR-mutant subgroup included 867 patients, and 75.2%, 11.2%, and 11.8% were classified as stage I, stage II, and stage III, respectively. Within the EGFR-mutant subgroup, 44 (5.1%) and 121 (14.0%) patients showed early and late recurrence, respectively. Multivariate analysis on association with postoperative relapse among the EGFR-mutant subgroup showed that age, pathologic N and TNM stages, pleural invasion status, and surgery type were independent significant factors. Conclusion Among the population that underwent complete resection for early NSCLC with EGFR mutation, patients with advanced stage, pleural invasion, or limited resection are more likely to show postoperative relapse.

Purpose: We aimed to identify changes in surgical indications in patients with ulcerative colitis (UC) in the biologics era in a single tertiary center. Methods: In this retrospective observational study, 108 patients with UC who underwent abdominal surgery for UC at Seoul National University Hospital from 2000 to 2021 were included. We compared the total number of patients undergoing UC before and after the introduction of biologic therapy. Results: Of the 108 patients with UC (male, 59 and female, 49; mean age, 46.8 years), 30 (27.8%) underwent surgery for neoplasms and 78 (72.2%) for medical intractability without neoplasms. The duration between diagnosis and surgery varied significantly (126.00 months vs. 60.50 months, P = 0.001). A significant difference was also noted in the surgical indications according to time (P = 0.02). Between 2000 and 2010, 12 patients (19.4%) underwent surgery for UC with neoplasms and 50 (80.6%) for UC without neoplasms, while between 2011 and 2021, 18 (39.1%) and 28 patients (60.9%) underwent surgery for UC with and without neoplasms, respectively. Conclusion Since 2011, when biological agents were covered by insurance in South Korea, there has been a relative increase in the incidence of surgical indications for neoplasia cases. Focusing on closely monitoring individuals with longterm UC for neoplasms is necessary.