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: Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) in children, with a rising incidence of macrolide resistance. Early diagnosis is crucial for reducing the disease burden; however, current diagnostic tools have limitations.We evaluated the diagnostic accuracy of serological assays and their performance based on symptom onset in children with CAP. Methods: From September 2023 to September 2024, we prospectively enrolled children with CAP, classified as M. pneumoniae pneumonia (MPP) or non-MPP, from 16 hospitals in Korea. Serological testing included chemiluminescence immunoassay (CLIA) and ELISA for detecting IgM and IgG, along with particle agglutination (PA) for total antibody measurements. Serological responses were analyzed at different times after symptom onset (0–4, 5–9, and 10–21 days). Results: Among 472 children with CAP (362 MPP, 110 non-MPP), 138 (29.2%) underwent PA testing, and 334 (70.8%) underwent IgM testing. PA at a 1:640 cutoff showed 48.0% sensitivity and 100% specificity. CLIA and ELISA showed comparable sensitivities (69.1% vs. 69.2%) and specificities (76.9% vs. 66.7%) for IgM testing. Seropositivity increased significantly with time since symptom onset (P for trend < 0.001), reaching 97.9% for IgM, 62.5% for IgG, and 94.7% for PA at 10–21 days. Conclusions The time post-symptom onset significantly influenced the diagnostic utility of serological tests for pediatric MPP, which showed limited value during the early stage of illness. These findings emphasize the importance of symptom onset-based interpretation of serological test results and their utility in complementing PCR when optimizing MPP diagnosis in children.

Background: A systematic evaluation of potential living liver donors is essential to ensure donor safety and optimize recipient outcomes in living donor liver transplantation (LDLT). This study aimed to assess donor acceptance rates and reasons for disqualification among individuals evaluated for LDLT at a high-volume transplant center over a one-year period. Methods: We retrospectively reviewed 1,087 potential living liver donors who presented for LDLT evaluation in 2023. Of these, 991 candidates advanced beyond the initial screening (Stage 1) and underwent comprehensive clinical, imaging, and pathological assessments (Stages 2 and 3). Candidates who discontinued after Stage 1 were excluded due to the absence of documented reasons for non-progression. Results: Among the 991 candidates who proceeded beyond initial screening, 473 (47.7%) completed the full donor evaluation, of whom 466 were judged to be suitable donors. Among suitable donors, 384 (82.4%) proceeded to donor hepatectomy, whereas 82 did not, primarily due to recipient-related factors such as clinical deterioration or withdrawal of consent. Donor ineligibility was determined in 422 candidates (42.6%), most commonly due to inadequate remnant liver volume (52.8%), hepatic steatosis (20.6%), and insufficient graft size (10.2%). Among candidates undergoing Stage 2 evaluation, 162 (16.3%) failed to meet steatosis criteria; 126 were excluded solely for steatosis and advised weight reduction, and 39 subsequently became eligible and successfully donated. Conclusion In this high-volume LDLT center, donor disqualification was primarily driven by remnant liver volume and hepatic steatosis. Targeted interventions such as weight reduction enabled successful donation in a subset of initially ineligible candidates, underscoring the importance of individualized donor evaluation and pre-donation optimization.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global health issue due to its increasing prevalence associated with lifestyle changes and its strong correlation with metabolic syndrome. Farnesoid X receptor (FXR) is a nuclear receptor that plays a pivotal role in regulating bile acid, lipid, and glucose metabolism, making it an attractive therapeutic target for liver and metabolic diseases. In this study, we investigated the effects of MHY5456, a synthetic agonist of FXR, on hepatic metabolism and fibrosis. MHY5456 enhanced the transcriptional activity of FXR in a concentration-dependent manner.Treatment of AC2F rat liver-derived cells with MHY5456 resulted in the downregulation of genes involved in lipid accumulation and an upregulation of mitochondrial-related gene expression. Additionally, MHY5456 significantly reduced oleic acid (OA)-induced lipid accumulation. To assess its anti-fibrotic potential, we tested its effects on transforming growth factor-beta (TGF-β)-induced fibrosis in LX2 human hepatic stellate cells (HSCs). MHY5456 significantly suppressed the expression of fibrosis-related genes and proteins. In vivo, administration of MHY5456 to mice fed a methionine-choline-deficient (MCD) diet alleviated hepatic fibrosis, inflammation, and lipid accumulation. These results show that FXR activation by MHY5456 modulates lipid metabolism and fibrotic pathways, suggesting its potential as a pharmacological candidate for liver and metabolic disorders, including MASLD. Further pharmacological and toxicological studies are needed to confirm its therapeutic relevance.

Background: This study aims to compare the effects of short- and intermediate-acting erythropoiesis-stimulating agents (ESAs) on hemoglobin (Hb) variability in patients undergoing maintenance hemodialysis. Methods: This retrospective cohort study included 119 patients who were classified into two groups based on ESA type: short-acting ESA (epoetin alfa/beta [EPO], n=48) and intermediate-acting ESA (darbepoetin alfa [DPO], n=71). Hb levels were measured 11 times at 4-week intervals from ESA therapy initiation to 40 weeks of follow-up. This study used established metrics from previous research, including standard deviation (SD), coefficient of variation (CV), and residual SD, to quantify Hb variability. Results: Over the 40-week study period with 4-week measurement intervals, mean Hb levels were comparable between the two ESA groups. In the EPO and DPO groups, SD was 0.67±0.19 g/dL and 0.69±0.22 g/dL, respectively (p=0.516), CV was 0.06±0.02 and 0.07±0.02, respectively (p=0.480), and residual SD was 0.73±0.21 g/dL and 0.76±0.26 g/dL, respectively (p=0.463). No significant differences in Hb variability were observed between the groups over 40 weeks using SD, CV, and residual SD. Conclusion This retrospective cohort study showed comparable mean Hb levels and Hb variability indices between groups. With respect to Hb variability, the findings reveal no clear basis for prioritizing either short-acting or intermediate-acting ESA.

In patients with differentiated thyroid cancer (DTC), initial recurrence risk stratification based on clinical, histopathological, and perioperative data remains the key determinant for guiding management strategies during the first 1-2 years post-treatment. However, the adoption of ongoing risk stratification (ORS), which dynamically reassesses risk by integrating longitudinal clinical data and treatment response, enables more precise long-term prognostic assessment and facilitates highly individualized management. Building upon recent guidelines, the 2026 KTA guideline has been further refined by incorporating robust evidence from large-scale national cohorts and comprehensive systematic reviews. These updated recommendations outline contemporary concepts of ORS, risk-adapted TSH suppression targets, optimized surveillance modalities for recurrence detection, and disease-specific long-term follow-up strategies. Reflecting the paradigm shift toward de-escalated treatment, this revision integrates evolved perspectives on TSH suppression intensity, the clinical interpretation of thyroglobulin levels, and tailored follow-up intervals. These evidence-based recommendations aim to minimize unnecessary treatment and excessive surveillance in the large proportion of patients with excellent prognosis after initial therapy, while ensuring that each patient receives appropriately tailored and effective long-term management.

Hepatocellular carcinoma (HCC) is a highly invasive tumor with a strong tendency for metastasis. The most common sites of metastasis are the lungs, followed by lymph nodes, adrenal glands, and bones. However, metastasis of HCC to the small bowel is extremely rare. A 42-yearold female with HCC secondary to chronic hepatitis B and lung metastasis underwent a right hepatic lobectomy, followed by two wedge resections performed via video-assisted thoracic surgery, four sessions of transcatheter arterial chemoembolization, and stereotactic body radiation therapy. She was under regular follow-up for HCC, during which her alpha-fetoprotein level increased to 722.2 IU/ml. Abdominal computed tomography (CT) revealed segmental wall thickening and aneurysmal dilatation of the small bowel loops. An 18 F-fluorodeoxyglucose positron emission tomography/CT scan demonstrated a 3.3-cm hypermetabolic mass-like lesion (standardized uptake value: 11.3) in the small bowel. Surgical resection of the affected small bowel segment was performed. Histopathological examination of the specimen confirmed metastatic HCC, with immunohistochemical positivity for hepatocyte-specific antigen. The patient has remained cancer-free for 60 months post-operatively. Surgical intervention may offer favorable long-term outcomes in patients with small bowel metastasis from HCC.

Background: Graft failure (GF) is a major complication of allogeneic hematopoietic cell transplantation (allo-HCT). Secondary transplantation has been recognized as a potential curative intervention. Methods: This study aimed to investigate the characteristics and outcomes of salvage transplantation by analyzing the patients who underwent a second HCT for GF following the initial allo-HCT between 1998 and 2020. Results: Overall, 23 recipients were identified, including 14 and 9 individuals with primary and secondary GF, respectively. Nine recipients underwent a second transplant from the same donor. Familial mismatched donors predominated in the second HCT (86.9%), with reduced-intensity conditioning as the prevailing approach (60.9%). Neutrophil engraftment occurred in 17 patients (73.9%) following the second HCT at a median of 17 days (range: 9–58 days) post-transplantation. However, secondary GF subsequently occurred in 5 patients, and successful engraftment following salvage transplantation was achieved in 12 (52.2%) patients. In the entire study population, the estimated 5-year probability of overall survival (OS) and treatment-related mortality (TRM) were 30.4% and 58.5%, respectively. Among patients who achieved successful engraftment following a second transplantation, the OS and TRM rates were 41.7% and 33.3%, respectively, indicating a trend toward better OS and significantly lower TRM compared to those with GF. Notably, 17 patients died, with infection being the most common cause (n = 12), irrespective of the engraftment status. Conclusion A successful engraftment following a second allo-HCT reduced the TRM; however, the OS remained suboptimal. The effective control of infectious diseases remains crucial for patients with GF, regardless of the engraftment status following salvage transplantation.

Background and Objectives: Among various emerging catheter-based treatments for severe tricuspid regurgitation (TR), the spacer device can reduce the regurgitation orifice without manipulating the valve leaflet. However, its clinical application has been hampered by traumatic anchoring to the myocardium and the coaxial alignment of the balloon resulting in insufficient TR reduction. This study aimed to evaluate the early-stage safety, technical feasibility, and preliminary efficacy of the novel atraumatic vertical spacer in patients with isolated severe TR. Methods: All procedures were guided by fluoroscopy and transthoracic echocardiography.The maximum device placement time with an inflated balloon was 24 hours. Changes in the amount of TR, right ventricular function, and patient hemodynamics were measured during balloon deployment. Results: A total of 7 patients (median age 74), underwent successful device implantation without procedure-related complications. During balloon inflation (median 25 minutes), there were no symptoms or signs indicative of TR intolerance. TR was reduced by 1 grade or greater in all patients, with 2 patients exhibiting a reduction of 3 grades, from torrential TR to a moderate degree. Mild TR after balloon inflation was achieved in 3 patients with baseline severe TR. The TR reduction observed during initial balloon deployment was sustained during the subsequent balloon maintenance period. Conclusions The Pivot-balloon procedure was safe, technically feasible, and effective in reducing TR in patients with severe TR. No periprocedural complications or adverse cardiovascular events were reported during device placement with TR reduction observed in all patients. However, longer-term follow-up is needed to confirm safety and treatment effect.