Background: As nationwide government-led whole-genome sequencing (WGS) projects progress, optimizing the clinical integration of large-scale WGS results is crucial. We explored how the initial analysis from Korea’s First WGS Pilot Study for Rare Diseases was applied in clinical practice, and then we reanalyzed the data comprehensively at Samsung Medical Center (SMC) Seoul, Korea. Methods: A prospective cohort study designed to collect WGS data under a Korean national initiative was conducted from August 2020 to December 2021. We focused on patients with rare diseases recruited from 16 university hospitals. The participants included 5,000 individuals (2,200 probands and 2,800 family members). The initial WGS data and diagnostic reference reports (from 682 probands and 484 family members), generated based on the First Korean WGS Pilot Study for Rare Diseases, were subsequently reanalyzed by SMC. Results: The initial analysis of the First Korean WGS Pilot Study data revealed a diagnostic rate of 17%. Upon receiving these results, the SMC conducted two rounds of reanalysis, increasing the diagnostic rate from 15% in the first analysis, to 18% in the second, and finally to 24% in the third (P = 1.6 × 10 −5 ). Key factors in improving the genetic diagnosis included increased detection of novel (likely) pathogenic variants (P = 1.0 × 10 −4 ), improved diagnostic rates with larger family recruitment (P = 0.004), and refined clinical information for more precise genotype–phenotype correlation analysis (40%). Conclusions Although national WGS projects lay a foundation for rare disease diagnosis, hospital-level reanalysis and multidisciplinary collaborations are crucial for optimizing diagnostic outcomes.

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.

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: Alectinib has been approved for anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC) at 300 mg twice daily in Japan, lower than global standard of 600 mg twice daily. This study evaluated the clinical relevance of the reduced dose by comparing outcomes between the two doses. Materials and Methods: This study included patients with advanced ALK-positive NSCLC who received alectinib at Samsung Medical Center, Korea. The progression-free survival (PFS), overall survival, cumulative incidence of central nervous system (CNS) progression, and safety profiles were retrospectively reviewed and compared. Results: Among 306 patients, 32 and 274 received alectinib at either 300 or 600 mg twice daily, respectively. The 300 mg group showed a slight but not significant advantage in PFS (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.44 to 1.51; p=0.51) and overall survival (HR, 0.51; 95% CI, 0.20 to 1.21; p=0.13). Superior outcome with 300 mg was remarkable in patients with lower body weight (≤ 60 kg), but diminished in patients with higher body weights. Patients with baseline brain metastasis in the 300 mg group exhibited a slight increase in incidence of CNS failure (HR, 1.76; 95% CI, 0.53 to 5.8; p=0.36). Although the safety profiles were mostly mild, adverse events were more frequent in the 600 mg group, 50% of which requiring dose reduction. Conclusion Alectinib at 300 mg twice daily seems an acceptable dose in East Asians with ALK-positive NSCLC. Notably, our data favor 300 mg twice daily in patients with lower body weight and no baseline brain metastasis, considering the more tolerable safety profiles and the potential to reduce medical costs.

Purpose: The aim of this study is to compare the detection ability of quality of life (QoL) changes and responsiveness of the KOrean QUality of life in Stomach cancer patients Study group (KOQUSS)-40 and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Materials and Methods: A multicenter prospective observational study was conducted to evaluate QoL changes after various gastrectomies between January 2021 and April 2022. Participants were instructed to complete the KOQUSS-40 and EORTC QLQ-C30/STO22 preoperatively and at 1, 3, 6, and 12 months postoperatively. QoL changes over time and QoL responsiveness were assessed for each questionnaire. Results: Data from 491 patients who underwent curative gastrectomy for gastric cancer at 22 institutions were analyzed. The summary scores of the KOQUSS-40 and EORTC QLQ-STO22 showed significant differences between the total and proximal gastrectomy groups (p=0.044 and p=0.038, respectively), but no difference was observed for the EORTC QLQ-C30. Dysphagia on the KOQUSS-40 was significantly different between the total and proximal gastrectomy groups (p=0.031); however, dysphagia on the EORTC QLQ-STO22 did not differ. The responsiveness of the KOQUSS-40 was similar to that of the EORTC QLQ in patients who experienced ≥ 10% body weight loss, but approximately 10% less in patients receiving adjuvant chemotherapy than the EORTC QLQ. Conclusion KOQUSS-40 has several advantages over EORTC QLQ-C30/STO22 when comparing QoL between the total and proximal gastrectomy groups. The findings provide information for researchers investigating the QoL of patients who have undergone curative gastrectomy for gastric cancer.

To compare optic nerve head (ONH) and peripapillary structural OCT parameters between eyes with and without visual field (VF) defects one year after an episode of acute primary angle closure (APAC) in a cohort treated uniformly treated with early clear-lens extraction. Forty-seven eyes of 47 patients with a history of APAC episode who underwent early clear-lens extraction at Chonnam National University Hospital were retrospectively reviewed. Spectral-domain optical coherence tomography (SD-OCT) performed one year after the episode was used to assess Bruch’s membrane opening-minimum rim width (BMO-MRW), retinal nerve fiber layer (RNFL) thickness, lamina cribrosa (LC) thickness and depth, and parapapillary atrophy (PPA) subdivided into PPA+BM and PPA−BM. Patients were classified according to the presence or absence of VF defects. At one year, 23 eyes (48.9%) had variable degrees of visual field (VF) defects. Compared with eyes with normal VF, the VF-defect group showed significantly thinner global BMO-MRW (p<0.001) and peripapillary RNFL (p<0.001), reduced LC thickness (p<0.001), shallower LC depth (p=0.028), and a wider PPA+BM (p<0.001). APAC patients who underwent early lens extraction may develop residual VF defect despite normalization of IOP. These defects were associated with structural damage in the rim, RNFL, LC, and PPA+BM as detected by SD-OCT. Comprehensive OCT analysis may help identify patients at risk of long-term functional sequelae after APAC.

Objective: To characterize age-related motor, olfactory, and auditory changes in 5×FAD mice and assess associated AD pathologies and neuroinflammation in relevant brain regions. Methods: 5×FAD and control mice were tested at 3, 6, and 12 months. Locomotor activity and motor coordination were assessed using the open field and rotarod tests, respectively. Olfactory and auditory performance were evaluated using the buried food test and the acoustic startle response test, respectively. Amyloid-β pathology and glial activation were examined in relevant nervous system components using western blot and immunohistochemistry analyses. Results: 5×FAD mice showed no differences in open-field locomotion at any age, but exhibited a significantly greater passive clinging duration at 12 months compared to wild-type controls (p < 0.001). In the buried food test, olfactory latency was significantly prolonged in 5×FAD mice at 6 months (p = 0.035) and 12 months (p < 0.001). Acoustic startle amplitude was significantly reduced at 6 months (p = 0.030) and 12 months (p = 0.007). Amyloid-β and p-Tau accumulation and glial activation were elevated in the olfactory bulb and auditory cortex in an age-dependent manner. Conclusions and Relevance: This study provides an age-related behavioral and pathological characterization of olfactory and auditory impairments in the 5×FAD mouse model, with motor measures included as complementary assessments. Our findings broaden the spectrum of functional deficits associated with the AD pathology in this model.

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: Pulmonary rehabilitation (PR) is a key intervention for chronic obstructive pulmonary disease (COPD); however, adherence remains suboptimal, particularly in patients with low physical activity (PA) despite preserved physical capacity (PC). This study aimed to identify factors associated with low PA, with a focus on patient-reported outcomes (PROs). Methods: In this prospective study, COPD patients were categorized according to daily moderate-to-vigorous PA measured using Fitbit devices: ≥30 minutes/day (‘Do do’) and <30 minutes/day (‘Don’t do’). Baseline characteristics, pulmonary function, and exercise capacity assessed by 6-minute walk distance (6MWD) were evaluated. PROs included the modified Medical Research Council (mMRC) dyspnea scale, COPD Assessment Test (CAT), and Patient Health Questionnaire-9 (PHQ-9). Logistic regression analysis was performed to identify factors independently associated with low PA. Results: Among 96 patients, 44 were classified as ‘Do do’ and 52 as ‘Don’t do.’ The ‘Don’t do’ group showed significantly lower 6MWD (424 m vs. 488 m, p=0.005) and lower forced expiratory volume in 1 second (46.73% vs. 54.48%, p=0.005). They also reported higher dyspnea scores (mMRC 1.77 vs. 1.30, p=0.019). Greater breathlessness measured by CAT was independently associated with low PA (odds ratio, 1.31; 95% confidence interval, 1.06 to 1.62), even after adjustment for 6MWD and pulmonary function. This association persisted in patients with preserved PC. Conclusion Low PA in COPD is influenced not only by objective physical limitations but also by subjective symptom burden, particularly dyspnea. Integrating PROs into PR assessment may facilitate identification of barriers and improve adherence to rehabilitation programs.

Background: Vitamin D deficiency has been linked to increased risks of fractures and cardiovascular (CV) events, but the clinical relevance of the ‘insufficiency’ range remains unclear. We investigated CV and fracture risks across vitamin D levels, with a focus on the insufficiency range. Methods: Using UK Biobank data, we analyzed 375,044 participants aged 40 to 69 years. Vitamin D status was categorized as deficient (<50 nmol/L), insufficient (≥50 to <75 nmol/L), or sufficient (≥75 nmol/L). Outcomes included three-point major adverse cardiovascular events (3P-MACE; myocardial infarction, stroke, and CV mortality) and major osteoporotic fractures, assessed via hospital records, registries, and death certificates. Results: The vitamin D-deficient group had an increased risk of CV events (adjusted hazard ratio [aHR], 1.17; 95% confidence interval [CI], 1.11 to 1.24) and fractures (aHR, 1.09; 95% CI, 1.01 to 1.18) compared to the vitamin D-sufficient group. Within the deficient group, the severely deficient group (<30 nmol/L) exhibited a markedly higher risk (aHR, 1.29; 95% CI, 1.21 to 1.37 for 3PMACE; and aHR, 1.20; 95% CI, 1.10 to 1.32 for fractures). In contrast, the vitamin D-insufficient group (50 to 75 nmol/L) showed no significant increase in the risk of either outcome, with no clear benefit or harm observed. Spline curve analysis revealed a negative correlation between vitamin D levels and risk, which was observed only within the deficient range and not within the insufficient range. Conclusion Vitamin D deficiency is strongly associated with increased CV disease and fracture risks, whereas the insufficiency range shows no significant risk or benefit, raising questions about its clinical relevance.