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.

Background: Long working hours have been associated with adverse physical and mental health outcomes; however, evidence regarding their relationship with satisfaction with work environment remains limited, particularly when long working hours are defined using a specific daily threshold. This study examined the association between working ≥10 hours per day and satisfaction with work environment among Korean wage workers, focusing on the cumulative number of such workdays per month. Methods: This cross-sectional study analyzed data from the 7th Korean Working Conditions Survey. A total of 24,269 wage workers aged ≥18 years were included after excluding self-employed workers, unpaid family workers, shift workers, and respondents with missing data. Working ≥10 hours per day was categorized as 0, 1–9, and ≥10 days per month. Satisfaction with work environment was categorized as satisfied or dissatisfied. Multiple logistic regression analyses were conducted to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for dissatisfaction with work environment according to the number of long working days, adjusting for demographic and occupational characteristics. Results: Compared with workers who did not work ≥10 hours per day, those who worked 1–9 days and ≥10 days per month showed progressively higher levels of dissatisfaction with work environment. After adjustment for demographic and occupational factors, the odds of dissatisfaction with work environment were significantly higher among workers who worked ≥10 hours per day for 1–9 days per month (OR: 1.380; 95% CI: 1.145–1.665) and ≥10 days per month (OR: 2.106; 95% CI: 1.627–2.725), demonstrating a dose–response relationship. Conclusions Among the analytic sample of Korean wage workers included in this study, working ≥10 hours per day was associated with greater dissatisfaction with work environment, with a dose–response pattern according to the number of long working days per month.

Background: The prevalence of diabetes mellitus and early-onset dementia (EOD), defined as dementia diagnosed at an age <65 years, is increasing worldwide, with significant socioeconomic implications. We investigated the association between diabetes, prediabetes, and EOD, focusing on the influence of diabetes duration on EOD risk. Methods: Using the Korean National Health Insurance Service database, we analyzed data from 1,979,509 patients aged 40–60 years who underwent health checkups in 2009. Patients were categorized into five groups: normal, impaired fasting glucose (IFG), newly diagnosed diabetes, diabetes duration <5 years, and diabetes duration ≥5 years. Cox proportional hazard models were used to estimate the adjusted hazard ratios (aHRs) for EOD after adjusting for demographic and clinical covariates. Results: During the observation period (mean 7.75 years), 8,921 patients with EOD were identified. The diabetes group demonstrated a significantly higher incidence of EOD compared to the normal group (aHR, 1.334; 95% confidence interval [CI], 1.226 to 1.451). EOD risk increased with longer diabetes duration, with the highest risk observed in patients with diabetes ≥5 years (aHR, 1.543; 95% CI, 1.368 to 1.741). No significant difference was observed between the IFG and normal groups (aHR, 0.989; 95% CI, 0.938 to 1.043). Additionally, the hypertension group exhibited a significantly higher incidence of EOD compared to the non-hypertension group (aHR, 1.364; 95% CI, 1.291 to 1.442). Conclusion Diabetes is independently associated with increased risk of EOD, and this risk increases with longer diabetes duration. This association remained significant regardless of the presence and duration of hypertension.

Extraskeletal Ewing sarcoma (EES) is a rare, malignant small round-cell tumor, and involvement of the spinal epidural space is unusual. Here, we report a case of spinal epidural EES in a 46-year-old man who presented with back pain. Magnetic resonance imaging revealed a dumbbell-shaped right paravertebral mass extending through the ipsilateral neural foramen, with focal bone marrow infiltration. After surgical resection and adjuvant chemoradiotherapy, progressive bone marrow involvement and vertebral metastasis were observed on follow-up imaging. This case highlights the diagnostic challenges of epidural EES and underscores the importance of recognizing bone marrow involvement, which is rare in EES.

Background: Left bundle branch block (LBBB) significantly increases the risk of left ventricular systolic dysfunction (LVSD) due to cardiac dyssynchrony. Although artificial intelligence–enabled electrocardiography (AI-ECG) mod‑ els show promise in detecting LVSD, their performance in LBBB patients remains underexplored. We hypothesized that an AI-ECG model clinically validated for detecting LVSD would accurately detect LVSD and predict future clinical outcomes in LBBB patients. Methods: In this retrospective multicenter study, 5,689 expert-validated LBBB ECGs collected from 2,813 patients between 2016 and 2024 were analyzed using a previously developed and validated AI-ECG model. LVSD was defined as an ejection fraction of ≤ 40%. Model performance was assessed using the area under the receiver operating char‑ acteristic curve (AUROC), the area under the precision-recall curve (AUPRC), sensitivity, and specificity. Patients were stratified into high- and low-risk groups based on a threshold that achieved 90% sensitivity. A Kaplan–Meier analysis was used to compare clinical outcomes. Results: Among the 2,813 LBBB patients (mean age, 70.7 years; male sex, 43.7%), hypertension and a history of heart failure were common. The AiTiALVSD model showed strong diagnostic performance for LVSD (AUROC, 0.930 [95% CI, 0.924–0.937]; AUPRC, 0.913 [95% CI, 0.902–0.923]; sensitivity, 0.979; specificity, 0.473). During the mean follow-up of 4.1 years, high-risk patients had significantly higher hazards than low-risk patients for all-cause mortality (adjusted hazard ratio [HR], 1.87; 95% CI, 1.53–2.28), implantable cardioverter defibrillator/cardiac resynchronization therapy implantation (adjusted HR, 15.2; 95% CI, 7.51–30.77), and cardiovascular hospitalization (adjusted HR, 1.11; 95% CI, 0.96–1.28). Conclusions AiTiALVSD effectively detects LVSD and stratifies long-term cardiovascular risk in LBBB patients, support‑ ing its clinical utility for early detection and patient management.

Objective: We investigated the distribution of AI viruses in fecal samples from wild bird habitats (and nearby poultry-farm areas) surveyed between September and March from 2019 to 2025 and identified associated epidemiological risk factors. Methods: Samples were screened for influenza A (M, H5, H7) genes using real-time reverse transcription polymerase chain reaction (PCR), subjected to virus isolation in embryonated chicken eggs, and subtyped by PCR and sequencing. Host species were identified through DNA barcoding. Relative risks (RRs) with 95% confidence intervals were estimated for province, month, and waterfowl density. Results: Overall prevalence of HPAI and low pathogenic AI (LPAI) virus was 0.10% and 3.21%, respectively. HPAI virus was continuously isolated since 2020–2021, except 2019– 2020, while LPAI prevalence steadily increased (3.01%–4.35%). Twelve hemagglutinin (H1–H12) subtypes were identified in 1,722 isolates, and H3 (16.5%) was the most prevalent, followed by H5 (11.1%) and H7 (5.2%). LPAI H5N3 (55.7%) and H7N7 (75.5%) were the predominant H5 and H7 subtypes, respectively. Detection was higher in western coastal provinces, and higher mallard/spot-billed duck density and sampling in September– December were associated with increased risk. Conclusions and Relevance: Continued surveillance of migratory-bird habitats can provide early warning of HPAIV incursions and support targeted biosecurity measures in high-risk regions and seasons.

Background: With the aging population and advancements in medical care worldwide, the number of older patients with end-stage kidney disease continues to rise. This study aimed to identify factors associated with osteoporosis and osteopenia in older patients undergoing incident hemodialysis and assess their impact on mortality. Methods: We analyzed a large multicenter retrospective cohort of patients aged ≥70 years undergoing incident hemodialysis to identify factors associated with osteoporosis using logistic regression analysis and to assess the association of death with osteoporosis and osteopenia using Cox multivariable analysis. Results: Among 710 patients, 39.0% and 19.6% had osteoporosis and osteopenia, respectively. Osteoporosis was significantly associated with female sex, a history of fractures, and the absence of phosphate binder use. During a median follow-up of 36.8 months, 348 participants (58.8%) died. Mortality rates were the highest in the osteoporosis group (79.8%), followed by the osteopenia (77.2%) and normal bone mineral density (BMD) groups (35.2%). Cox regression analysis revealed that even after adjusting for covariates, the osteoporosis group was significantly associated with a higher mortality risk than the normal BMD group. Osteoporosis at the start of hemodialysis was significantly associated with higher mortality. Conclusion We should consider the importance of bone health in patients undergoing incident hemodialysis and pay attention to the use of phosphate binders and fracture prevention.

Background: Obesity is a well-known risk factor for chronic kidney disease and its progression. However, the impact of obesity on the renal function of the elderly population is uncertain. We investigated the association between obesity and renal outcomes in the elderly. Methods: We analyzed 130,504 participants from the Korean National Health Insurance Service-Senior cohort. Obesity was classified according to body mass index (BMI), sex-specific waist circumference (WC), and the presence of metabolic syndrome. The primary outcome was renal function decline, defined as a decline in the estimated glomerular filtration rate (eGFR) of at least 50% from baseline or new-onset end-stage renal disease. Results: During a follow-up period of 559,531.1 person-years (median, 4.3 years), 2,486 participants (19.0%; incidence rate of 4.44 per 1,000 person-years) showed renal function decline. A multivariate Cox proportional hazards model revealed that BMI/WC was not associated with renal function decline. However, the group with metabolic syndrome had a significantly increased risk of renal function decline compared to the group without metabolic syndrome (adjusted hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.13–1.36). Compared with the non-metabolic syndrome group, the adjusted HRs (95% CI) for participants with one through five components were 0.96 (0.84–1.11), 1.10 (0.96–1.27), 1.24 (1.06–1.45), 1.37 (1.12–1.66), and 1.99 (1.42–2.79), respectively (p for trend < 0.001). Conclusion In elderly Korean adults, metabolic syndrome and the number of its components were associated with a higher risk of renal function decline, but BMI or WC was not significant.

The initial molecular cytogenetic characteristics of blasts plays a significant role in determining the treatment course of B-cell acute lymphoblastic leukemia (B-ALL).B-ALL with intrachromosomal amplification of chromosome 21 (iAMP21) has been well known to have unfavorable prognosis. Also, there are previously recognized germline mutations that increase the risk of ALL, such as trisomy 21, Down syndrome. This case report is about a 16-year-old girl who presented with lymphadenitis, purpura, and fever followed by initial lab of elevated white blood cell with blasts.She had some notable facial features, but no typical Down syndrome related one.Bone marrow biopsy and fluorescence in situ hybridization finalized the diagnosis as B-ALL with iAMP21, high-risk group. The minimal residual disease-negative complete remission was achieved after the induction chemotherapy with Korean multicenter high-risk protocol. However, abnormal karyotype was sustained in bone marrow. Microarrays with her buccal swab raised the possibility that the abnormal karyotype was not from the leukemic blasts but rather from the germline. Although she underwent scheduled chemotherapy uneventfully as slow early responder type, thrombocytopenia and abnormal karyotype persisted, leading to the diagnosis of acute myeloid leukemia. Additional chemotherapy and peripheral blood stem cell transplantation was performed which resulted in engraftment. This case highlights the discovery of a constitutional genetic aberration, which played like a silent yet critical background factor for B-ALL with iAMP21. As the number of reported cases are limited, the role of germline chromosome 21 mutation as the indicator for prognosis of B-ALL should be studied further.

Background: The recent published Korean Working Group on Sarcopenia (KWGS) guideline includes the concept of functional sarcopenia. The study investigated the prevalence of sarcopenia and its association with health-related adverse outcomes defined by the KWGS in community-dwelling older adults. Methods: Data were sourced from the Korean Longitudinal Study on Health and Aging, focusing on Koreans 65 aged and above. The definitions of sarcopenia and functional sarcopenia followed the KWGS. The risks of falls, mobility limitation, and death were analyzed using logistic regression and Cox proportional hazard. Results: Of the 594 participants, 145 (24.4%) were classified as having functional sarcopenia and 129 (12.0%) with sarcopenia. Both showed an increased prevalence with age. Functional sarcopenia had higher risks of mobility limitation (odds ratio [OR]=3.461; 95% confidence interval [CI], 1.956–6.121) and mortality (hazard ratio [HR]=1.775; 95% CI, 1.229–2.564). Sarcopenia was associated with falls (OR=7.376; 95% CI, 1.500–36.272), mobility limitation (OR=2.057; 95% CI, 1.172–3.611) and mortality (HR=1.512; 95% CI, 1.054–2.169). Conclusion Functional sarcopenia is a prevalent condition that is associated with mobility limitation and mortality in community-dwelling older adults. This highlights the clinical relevance of functional sarcopenia and supports its inclusion in sarcopenia diagnosis.