Purpose: This study aimed to evaluate the prognosis of the not evaluated (NE) group by comparing it with the lost to follow-up (LTFU) group among patients with multidrug/rifampin-resistant tuberculosis (MDR/RR-TB). Materials and Methods: This was a retrospective longitudinal follow-up study using an integrated database constructed by data linkage of the three national databases. This database included 7226 cases of MDR/RR-TB notified between 2011 and 2017 in South Korea. Results: Among the 7226 MDR/RR-TB cases, 730 (10.1%) were classified as LTFU group, and 353 (4.9%) as NE group. When comparing NE group with LTFU group, there were no significant differences in the all-cause mortality rate (18.1% vs. 13.8%, p=0.065), median time to death [404 days (interquartile range, IQR 46–850) vs. 443 days (IQR 185–1157), p=0.140], and retreatment rate (26.9% vs.22.2%, p=0.090). After adjusting for potential confounders, the adjusted hazard ratio (aHR) for all-cause mortality (aHR 1.11; 95% confidence interval 0.80-1.53; p=0.531) in NE group was not significantly different than that in LTFU group. Among retreated cases, NE group had a higher treatment success rate (57.9% vs 43.8%, p=0.029) and a lower LTFU rate (11.6% vs 38.3%, p<0.001) compared to LTFU group. Conclusion NE group had an unfavorable outcome comparable to LTFU group, suggesting undetected cases of LTFU or deaths during the referral process. Establishing an efficient patient referral system would contribute to reducing the incidence of NE cases.

Background: Post-transplantation cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are common pro‑ phylactic strategies for graft-versus-host disease (GVHD) after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Interleukin (IL)-6 is a surrogate marker for cytokine release syndrome (CRS) and acute GVHD.Method The clinical outcomes and complications of haplo-HSCT with PTCy plus ATG versus PTCy monotherapy were compared according to serum IL-6 levels at Chungnam National University Hospital (Daejeon, South Korea) from Jan‑ uary 2019 to February 2023. Results: Forty patients who underwent haplo-HSCT were analyzed. A significant difference in IL-6 levels was observed between the PTCy plus ATG and PTCy alone groups (7.47 ± 10.55 vs. 117.65 ± 127.67; p = 0.003). More patients in the PTCy plus ATG group had a CRS grade of 0 than in the PTCy alone group (p < 0.001). Serum IL-6 levels were associated with grades II–IV acute GVHD (r = 0.547, p < 0.001). The cumulative incidence (CI) of grades II–IV acute GVHD was significantly higher in the PTCy alone group (67.9% vs. 4.8%; p < 0.001). No significant difference in the CI for chronic GVHD was detected between the PTCy plus ATG and PTCy alone groups (72.1% vs. 82.0%; p = 0.730). The CI of 1-year non-relapse mortality was significantly higher in the PTCy alone group than in the PTCy plus ATG group (42.2% vs. 15.9%; p = 0.022). The 1-year overall survival (OS) was significantly better in the PTCy plus ATG group (75.9% vs. 35.3%; p = 0.011). The 1-year GVHD-free, relapse-free survival rate was 29.4% in the PTCy alone group and 54.0% in the PTCy plus ATG group (p = 0.038). Conclusion Serum IL-6 levels were higher in the PTCy alone group than in the PTCy plus ATG group. The addition of ATG before stem cell infusion affected IL-6 levels and reduced the incidences of CRS and grade II–IV acute GVHD in haplo-HSCT patients. This study suggests that PTCy plus ATG as GVHD prophylaxis in haplo-HSCT is beneficial in terms of clinical outcomes and complications of HSCT.

Purpose: Cancer poses a significant global health challenge, demanding precise genomic testing for individualized treatment strategies. Targeted-panel sequencing (TPS) has improved personalized oncology but often lacks comprehensive coverage of crucial cancer alterations. Whole-genome sequencing (WGS) addresses this gap, offering extensive genomic testing. This study demonstrates the medical potential of WGS. Materials and Methods: This study evaluates target-enhanced WGS (TE-WGS), a clinical-grade WGS method sequencing both cancer and matched normal tissues. Forty-nine patients with various solid cancer types underwent both TE-WGS and TruSight Oncology 500 (TSO500), one of the mainstream TPS approaches. Results: TE-WGS detected all variants reported by TSO500 (100%, 498/498). A high correlation in variant allele fractions was observed between TE-WGS and TSO500 (r=0.978). Notably, 223 variants (44.8%) within the common set were discerned exclusively by TE-WGS in peripheral blood, suggesting their germline origin. Conversely, the remaining subset of 275 variants (55.2%) were not detected in peripheral blood using the TE-WGS, signifying them as bona fide somatic variants. Further, TE-WGS provided accurate copy number profiles, fusion genes, microsatellite instability, and homologous recombination deficiency scores, which were essential for clinical decision-making. Conclusion TE-WGS is a comprehensive approach in personalized oncology, matching TSO500’s key biomarker detection capabilities. It uniquely identifies germline variants and genomic instability markers, offering additional clinical actions. Its adaptability and cost-effectiveness underscore its clinical utility, making TE-WGS a valuable tool in personalized cancer treatment.

The common data model (CDM) has found widespread application in healthcare studies, but its utilization in cancer research has been limited. This article describes the development and implementation strategy for Cancer Clinical Library Databases (CCLDs), which are standardized cancer-specific databases established under the Korea-Clinical Data Utilization Network for Research Excellence (K-CURE) project by the Korean Ministry of Health and Welfare. Fifteen leading hospitals and fourteen academic associations in Korea are engaged in constructing CCLDs for 10 primary cancer types. For each cancer type-specific CCLD, cancer data experts determine key clinical data items essential for cancer research, standardize these items across cancer types, and create a standardized schema. Comprehensive clinical records covering diagnosis, treatment, and outcomes, with annual updates, are collected for each cancer patient in the target population, and quality control is based on six-sigma standards. To protect patient privacy, CCLDs follow stringent data security guidelines by pseudonymizing personal identification information and operating within a closed analysis environment. Researchers can apply for access to CCLD data through the K-CURE portal, which is subject to Institutional Review Board and Data Review Board approval. The CCLD is considered a pioneering standardized cancer-specific database, significantly representing Korea’s cancer data. It is expected to overcome limitations of previous CDMs and provide a valuable resource for multicenter cancer research in Korea.

Background: Infantile hemangioma (IH) is a common benign vascular tumor that occurs during infancy. Oral propranolol is used as a first-line treatment. However, standardized guidelines for evaluating treatment efficacy, particularly the appropriate timing and parameters for Doppler ultrasound (US), have not been established. This study reports on the evaluation of therapeutic efficacy of oral propranolol solution in IH patients using Doppler US, and aims to propose the appropriate timing and parameters for using Doppler US based on this experience. Methods: A retrospective analysis was conducted on 120 patients with IH who were treated with oral propranolol solution and maintained for over 6 months from May 2017 to April 2023. Doppler US evaluation of IH was performed at diagnosis, 1-2 and 6-12 months after treatment initiation, and 6 months post-therapy cessation. A complete response (CR) was identified as a reduction in vascularity along with a decrease in longest diameter (LD) or thickness of 50% or more. Recurrence was evaluated based on increased vascularity or size 6 months after treatment discontinuation. Results: Of 120 patients with IH, 82 females and 38 males were analyzed. IH was first detected at a median age of 12 days (range, 1-240 days), and treatment began at 76 days (range, 27-570 days), continuing for an average of 10.4 months (range, 5-24 months). Initial Doppler US measurements showed an LD of 2.65±1.52 cm and a thickness of 0.79±0.55 cm, with prominent vascularity. After 1-2 months of treatment, LD and thickness decreased by 12.9% and 25.9%, respectively. By 6-12 months, reductions reached 37.2% and 53.6%. CR occurred in 77 patients (64.2%) after 6-12 months of treatment. Eleven patients (9.2%) experienced a recurrence. Conclusion Doppler US is a valuable modality for evaluating the characteristics, treatment response, and recurrence of IH treated with oral propranolol.

Background: Given the association between nonalcoholic fatty liver disease and metabolic risks, a new term, metabolic dysfunction- associated steatotic liver disease (MASLD) has been proposed. We aimed to explore the association between MASLD and all-cause, cause-specific mortalities. Methods: We included individuals with steatotic liver disease (SLD) from the Korean National Health Insurance Service. Moreover, SLD was defined as a fatty liver index ≥30. Furthermore, MASLD, metabolic alcohol-associated liver disease (MetALD), and alcoholic liver disease (ALD) with metabolic dysfunction (MD) were categorized based on alcohol consumption and MD. We also analyzed all-cause, liver-, cancer-, hepatocellular carcinoma (HCC)- and cardiovascular (CV)-related mortalities. Results: This retrospective nationwide cohort study included 1,298,993 individuals aged 40 to 79 years for a mean follow-up duration of 9.04 years. The prevalence of MASLD, MetALD, and ALD with MD was 33.11%, 3.93%, and 1.00%, respectively. Relative to the “no SLD” group, multivariable analysis identified that MASLD (adjusted hazard ratio [aHR], 1.28; 95% confidence interval [CI], 1.26 to 1.31), MetALD (aHR, 1.38; 95% CI, 1.32 to 1.44), and ALD with MD group (aHR, 1.80; 95% CI, 1.68 to 1.93) have a significantly higher risk of all-cause mortality. Furthermore, MASLD, MetALD, ALD with MD groups showed higher liver-, cancer- and HCC-related mortality than “no SLD” group. While all-cause specific mortalities increase from MASLD to MetALD to ALD with MD, the MetALD group shows a lower risk of CV-related mortality compared to MASLD. However, ALD with MD group still have a higher risk of CV-related mortality compared to MASLD. Conclusion SLD is associated with an increased risk of all-cause, liver-, cancer-, HCC-, and CV-related mortalities.

The liver plays a fundamental role in metabolic homeostasis, integrating systemic fuel utilization with the progression of various metabolic diseases. Hepatic stellate cells (HSCs) are a key nonparenchymal cell type in the liver, which is essential for maintaining hepatic architecture in their quiescent state. However, upon chronic liver injury or metabolic stress, HSCs become activated, leading to excessive extracellular matrix deposition and pro-fibrotic signaling, ultimately positioning them as key players in liver pathology. Emerging evidence highlights the critical roles of metabolic reprogramming and epigenetic regulation in HSCs activation. HSCs activation is driven by both intrinsic fuel metabolism reprogramming and extrinsic metabolic cues from the microenvironment, while the metabolic intermediates actively reshape the epigenetic landscape, reinforcing fibrogenic transcriptional programs. In this review, we summarize recent advances in understanding how metabolic and epigenetic alterations drive HSCs activation, thereby shaping transcriptional programs that sustain fibrosis, and discuss potential therapeutic strategies to target these interconnected pathways in human metabolic diseases.

Background: We aimed to investigate the predictive values of plasma C-peptide levels and the continuous glucose monitoring (CGM)-defined coefficient of variation (CV) in risk prediction for hypoglycemia in Korean people with diabetes with normal and impaired kidney function. Methods: We analyzed data from 1,185 participants diagnosed with type 1 and type 2 diabetes who underwent blinded professional CGM between January 2009 and May 2021 at outpatient clinics. We explored correlations among CGM-defined CV, plasma C-peptide levels, and time below range at <70 and 54 mg/dL across different kidney function categories. Results: In patients with chronic kidney disease (CKD) stages 1–2 (n=934), 89.3% who had a random plasma C-peptide level higher than 600 pmol/L exhibited a CV of ≤36%. Among those in CKD stage 3 (n=161) with a random plasma C-peptide level exceeding 600 pmol/L, 66.7% showed a CV of ≤36%. In stages 4–5 of CKD (n=90), the correlation between random C-peptide levels and CV was not significant (r=–0.05, P=0.640), including cases with a CV greater than 36% despite very high random plasma C-peptide levels. Random plasma C-peptide levels and CGM-assessed CV significantly predicted hypoglycemia in CKD stages 1–2 and 1–5, respectively. Conclusion The established C-peptide criteria in Western populations are applicable to Korean people with diabetes for hypoglycemic risk prediction, unless kidney function is impaired equivalent to CKD stage 3–5. The CGM-defined CV is informative for hypoglycemic risk prediction regardless of kidney function.

Background: Intellectual disability (ID) may be associated with an increased risk of diabetes mellitus (DM). However, evidence from longitudinal studies is scarce, particularly in Asian populations. Methods: This retrospective cohort study used representative linked data from the Korea National Disability Registration System and the National Health Insurance Service database. Adults (≥20 years) who received a national health examination in 2009 (3,385 individuals with ID and 3,463,604 individuals without ID) were included and followed until 2020. ID was identified using legal registration information. Incident DM was defined by prescription records with relevant diagnostic codes. Multivariable-adjusted Cox proportional hazards regression models were used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for DM risks in individuals with ID compared to those without ID. Results: Over a mean follow-up of 9.8 years, incident DM occurred in 302 (8.9%) individuals with ID and 299,156 (8.4%) individuals without ID. Having ID was associated with increased DM risk (aHR, 1.38; 95% CI, 1.23 to 1.55). Sensitivity analysis confirmed a higher DM risk in individuals with ID (aHR, 1.39; 95% CI, 1.24 to 1.56) than those with other disabilities (aHR, 1.11; 95% CI, 1.10 to 1.13) or no disability (reference). Stratified analysis showed higher DM risk in non-hypertensive subjects (aHR, 1.63; 95% CI, 1.43 to 1.86) compared to hypertensive subjects (aHR, 1.00; 95% CI, 0.80 to 1.26; P for interaction <0.001). Conclusion Adults with ID have an increased risk of developing DM, highlighting the need for targeted public health strategies to promote DM prevention in this population.

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.