1.Male preference for TERT alterations and HBV integration in young-age HBV-related HCC: implications for sex disparity
Jin Seoub KIM ; Hye Seon KIM ; Kwon Yong TAK ; Ji Won HAN ; Heechul NAM ; Pil Soo SUNG ; Sung Won LEE ; Jung Hyun KWON ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Jeong Won JANG
Clinical and Molecular Hepatology 2025;31(2):509-524
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits significant sex disparities in incidence, yet its molecular mechanisms remain unclear. We explored the role of telomerase reverse transcriptase (TERT) genetic alterations and hepatitis B virus (HBV) integration, both known major contributors to HCC, in sex-specific risk for HBV-related HCC.
Methods:
We examined 310 HBV-related HCC tissues to investigate sex-specific TERT promoter (TERT-pro) mutations and HBV integration profiles, stratified by sex and age, and validated with single-cell RNA sequencing (scRNA-seq) data.
Results:
Tumors predominantly exhibited TERT-pro mutations (26.0% vs. 0%) and HBV-TERT integration (37.0% vs. 3.0%) compared to non-tumorous tissues. While TERT-pro mutations increased with age in both sexes, younger males (≤60 years) showed marked predominance compared to younger females. Males had significantly more HBV integrations at younger ages, while females initially had fewer integrations that gradually increased with age. Younger males' integrations showed significantly greater enrichment in the TERT locus compared to younger females, alongside a preference for promoters, PreS/S regions, and CpG islands. Overall, TERT genetic alterations were significantly sex-differential in younger individuals (75.3% in males vs. 23.1% in females) but not in older individuals (76.9% vs. 83.3%, respectively). These alterations were associated with increased TERT expression. The skewed TERT abnormalities in younger males were further corroborated by independent scRNA-seq data.
Conclusions
Our findings highlight the critical role of TERT alterations and HBV integration patterns in the male predominance of HCC incidence among younger HBV carriers, offering insights for future exploration to optimize sex-specific patient care and HCC surveillance strategies.
2.Exploring methylation signatures for high de novo recurrence risk in hepatocellular carcinoma
Da-Won KIM ; Jin Hyun PARK ; Suk Kyun HONG ; Min-Hyeok JUNG ; Ji-One PYEON ; Jin-Young LEE ; Kyung-Suk SUH ; Nam-Joon YI ; YoungRok CHOI ; Kwang-Woong LEE ; Young-Joon KIM
Clinical and Molecular Hepatology 2025;31(2):563-576
Background/Aims:
Hepatocellular carcinoma (HCC) exhibits high de novo recurrence rates post-resection. Current post-surgery recurrence prediction methods are limited, emphasizing the need for reliable biomarkers to assess recurrence risk. We aimed to develop methylation-based markers for classifying HCC patients and predicting their risk of de novo recurrence post-surgery.
Methods:
In this retrospective cohort study, we analyzed data from HCC patients who underwent surgical resection in Korea, excluding those with recurrence within one year post-surgery. Using the Infinium Methylation EPIC array on 140 samples in the discovery cohort, we classified patients into low- and high-risk groups based on methylation profiles. Distinctive markers were identified through random forest analysis. These markers were validated in the cancer genome atlas (n=217), Validation cohort 1 (n=63) and experimental Validation using a methylation-sensitive high-resolution melting (MS-HRM) assay in Validation cohort 1 and Validation cohort 2 (n=63).
Results:
The low-risk recurrence group (methylation group 1; MG1) showed a methylation average of 0.73 (95% confidence interval [CI] 0.69–0.77) with a 23.5% recurrence rate, while the high-risk group (MG2) had an average of 0.17 (95% CI 0.14–0.20) with a 44.1% recurrence rate (P<0.03). Validation confirmed the applicability of methylation markers across diverse populations, showing high accuracy in predicting the probability of HCC recurrence risk (area under the curve 96.8%). The MS-HRM assay confirmed its effectiveness in predicting de novo recurrence with 95.5% sensitivity, 89.7% specificity, and 92.2% accuracy.
Conclusions
Methylation markers effectively classified HCC patients by de novo recurrence risk, enhancing prediction accuracy and potentially offering personalized management strategies.
3.Constitutional Chromosome 21 Abnormality in B-ALL with iAMP21 in a Patient Developing Treatment-Related Myelodysplastic Syndrome
Inhwa KIM ; Su Hyun YOON ; Sunghan KANG ; Kyung-Nam KOH ; Mi Young KIM ; Young-Uk CHO ; Sang-Hyun HWANG ; Seongsoo JANG ; Eul-Ju SEO ; Beom Hee LEE ; Sunghee MIN ; Hyunwoo BAE ; Ho Joon IM ; Hyery KIM
Clinical Pediatric Hematology-Oncology 2025;32(1):23-28
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.
4.The Challenge of Trans-Ulnar Basal Coronoid Fracture-Dislocations: A Surgical Strategy Based on the Pattern of Coronoid Fracture
Hyoung-Seok JUNG ; Hyun-Cheul NAM ; Min Su CHU ; Jae-Sung LEE
Clinics in Orthopedic Surgery 2025;17(2):300-307
Background:
The rarity and complexity of trans-ulnar basal coronoid fracture-dislocations pose significant challenges in treatment. This study aimed to categorize these fractures based on coronoid fracture patterns and propose tailored surgical approaches for each type. Additionally, we evaluated the functional and radiological outcomes among the patients managed using our treatment algorithm.
Methods:
A total of 19 patients who underwent open reduction and internal fixation for trans-ulnar basal coronoid fracture-dislocations between March 2018 and October 2022 were enrolled in this study. These patients were classified based on the coronoid fracture patterns associated with olecranon fractures: type 1 involved anteromedial facet (AMF) fractures, type 2 encompassed coronoid base and body fractures, and type 3 involved a combination of types 1 and 2. We made a midline longitudinal dorsal incision to facilitate the provisional fixation of the olecranon fragment to the distal metaphysis using a locking plate. Subsequently, we employed the over-the-top (type 1) and Taylor–Scham (type 3) approaches for direct coronoid process fixation with buttress plating.Type 2 fractures were approached via medial fascial exposure from the posterior ulnar cortex or through the olecranon fractures, and subsequently fixed with miniplates and screws. Bony union and joint articulation were assessed via plain radiographs, and functional outcomes were evaluated using range of motion and the Mayo Elbow Performance Score.
Results:
Among the 19 patients, 3 had type 1 fractures, 14 had type 2 fractures, and 2 had type 3 fractures. All fractures exhibited solid osseous union without subluxation or dislocation. The average flexion and extension arc was 119.47° ± 20.88°, with a mean flexion of 127.37° ± 13.37° and an average flexion contracture of 7.89° ± 10.04°. The average Mayo Elbow Performance Score was 82.63 ± 12.51 points. Qualitatively, patient outcomes were excellent in 5 patients, good in 9, and fair in 5.
Conclusions
Most of our patients presented with easily approachable coronoid base and body fractures. However, in AMF fractures of the coronoid process, a direct medial approach is required for buttress plating. We believe our study helps provide useful guidelines for making appropriate decisions in trans-ulnar basal coronoid fracture-dislocations .
5.Prevalence, Incidence, and Metabolic Characteristics of Young Adults with Type 2 Diabetes Mellitus in South Korea (2010–2020)
Ji Yoon KIM ; Jiyoon LEE ; Joon Ho MOON ; Se Eun PARK ; Seung-Hyun KO ; Sung Hee CHOI ; Nam Hoon KIM
Diabetes & Metabolism Journal 2025;49(2):172-182
Background:
This study aimed to examine trends in the prevalence, incidence, metabolic characteristics, and management of type 2 diabetes mellitus (T2DM) among young adults in South Korea.
Methods:
Young adults with T2DM were defined as individuals aged 19 to 39 years who met the diagnostic criteria for T2DM. Data from the Korean National Health Insurance Service-Customized Database (2010–2020, n=225,497–372,726) were analyzed to evaluate trends in T2DM prevalence, incidence, metabolic profiles, comorbidities, and antidiabetic drug prescription. Additional analyses were performed using the Korea National Health and Nutrition Examination Survey.
Results:
The prevalence of T2DM in young adults significantly increased from 1.02% in 2010 to 2.02% in 2020 (P<0.001), corresponding to 372,726 patients in 2020. Over the same period, the incidence rate remained stable within the range of 0.36% to 0.45%. Prediabetes prevalence steadily increased from 15.53% to 20.92%, affecting 3.87 million individuals in 2020. The proportion of young adults with T2DM who were obese also increased, with 67.8% having a body mass index (BMI) ≥25 kg/m² and 31.6% having a BMI ≥30 kg/m² in 2020. The prevalence of hypertension, dyslipidemia, and fatty liver disease also increased, reaching 34.2%, 79.8%, and 78.9%, respectively, in 2020. Although the overall pharmacological treatment rate remained low, the prescription of antidiabetic medications with weight-reducing properties increased over the study period.
Conclusion
The prevalence of T2DM among young adults in South Korea nearly doubled over the past decade. The strong association with obesity and metabolic comorbidities emphasizes the urgent need for targeted prevention and management strategies tailored to this population.
6.Predicting Mortality and Cirrhosis-Related Complications with MELD3.0: A Multicenter Cohort Analysis
Jihye LIM ; Ji Hoon KIM ; Ahlim LEE ; Ji Won HAN ; Soon Kyu LEE ; Hyun YANG ; Heechul NAM ; Hae Lim LEE ; Do Seon SONG ; Sung Won LEE ; Hee Yeon KIM ; Jung Hyun KWON ; Chang Wook KIM ; U Im CHANG ; Soon Woo NAM ; Seok-Hwan KIM ; Pil Soo SUNG ; Jeong Won JANG ; Si Hyun BAE ; Jong Young CHOI ; Seung Kew YOON ; Myeong Jun SONG
Gut and Liver 2025;19(3):427-437
Background/Aims:
This study aimed to evaluate the performance of the Model for End-Stage Liver Disease (MELD) 3.0 for predicting mortality and liver-related complications compared with the Child-Pugh classification, albumin-bilirubin (ALBI) grade, the MELD, and the MELD sodium (MELDNa) score.
Methods:
We evaluated a multicenter retrospective cohort of incorporated patients with cirrhosis between 2013 and 2019. We conducted comparisons of the area under the receiver operating characteristic curve (AUROC) of the MELD3.0 and other models for predicting 3-month mortality. Additionally, we assessed the risk of cirrhosis-related complications according to the MELD3.0 score.
Results:
A total of 3,314 patients were included. The mean age was 55.9±11.3 years, and 70.2% of the patients were male. Within the initial 3 months, 220 patients (6.6%) died, and the MELD3.0had the best predictive performance among the tested models, with an AUROC of 0.851, outperforming the Child-Pugh classification, ALBI grade, MELD, and MELDNa. A high MELD3.0score was associated with an increased risk of mortality. Compared with that of the group with a MELD3.0 score <10 points, the adjusted hazard ratio of the group with a score of 10–20 pointswas 2.176, and that for the group with a score of ≥20 points was 4.892. Each 1-point increase inthe MELD3.0 score increased the risk of cirrhosis-related complications by 1.033-fold. The risk of hepatorenal syndrome showed the highest increase, with an adjusted hazard ratio of 1.149, followed by hepatic encephalopathy and ascites.
Conclusions
The MELD3.0 demonstrated robust prognostic performance in predicting mortality in patients with cirrhosis. Moreover, the MELD3.0 score was linked to cirrhosis-related complications, particularly those involving kidney function, such as hepatorenal syndrome and ascites.
7.Poor Prognosis of Pneumococcal Co-Infection in Hospitalized Patients with COVID-19: A Propensity Score-Matched Analysis
Soyoon HWANG ; Eunkyung NAM ; Shin-Woo KIM ; Hyun-Ha CHANG ; Yoonjung KIM ; Sohyun BAE ; Nan Young LEE ; Yu Kyung KIM ; Ji Sun KIM ; Han Wook PARK ; Joon Gyu BAE ; Juhwan JEONG ; Ki Tae KWON
Infection and Chemotherapy 2025;57(1):172-178
The impact of Streptococcus pneumoniae coinfection on coronavirus disease 2019 (COVID-19) prognosis remains uncertain. We conducted a retrospective analysis of patients hospitalized with COVID-19 who underwent a pneumococcal urinary antigen (PUA) test to assess its clinical utility. Results showed that PUA-positive patients required more oxygen support, high-flow nasal cannula, and dexamethasone compared to PUA-negative patients.Furthermore, the significantly higher incidence of a National Early Warning Score ≥5 in the PUA-positive group (P<0.001) suggests that a positive PUA test is associated with a severe disease course. However, no significant difference in mortality was observed between the two groups, and antibiotics were used in almost all patients (96.2%). While the PUA test may help guide antibiotic use in COVID-19 patients, its interpretation should be approached with caution.
8.The Incidence of Occult Malignancy in Contralateral Risk Reducing Mastectomy Among Affected Breast Cancer Gene Mutation Carriers in South Korea
Cho Eun LEE ; Dong Seung SHIN ; Ki Jo KIM ; Seok Jin NAM ; Seok Won KIM ; Jonghan YU ; Byung Joo CHAE ; Se Kyung LEE ; Jai Min RYU ; Goo-Hyun MUN ; Jai-Kyong PYON ; Byung-Joon JEON ; Kyongje WOO ; Jeong Eon LEE
Journal of Breast Cancer 2025;28(1):1-10
Purpose:
Breast cancer gene (BRCA) mutation is a well-known risk factor for breast cancer, and clinical interest in prophylactic mastectomy has increased in recent years.We investigated patients who were BRCA mutation carriers and underwent contralateral risk-reducing mastectomy (RRM), focusing on the incidence of occult malignancy after contralateral RRM.
Methods:
Prospectively collected data of patients with breast cancer treated at a single institution were retrospectively reviewed. Patients who underwent RRM with BRCA mutation who underwent RRM between January 2010 and November 2023 were included in this study.Among patients who underwent contralateral RRM, those with a primary cancer diagnosis were included, and those with occult malignancy on the contralateral RRM side were reviewed additionally. The demographics and pathologies of both primary breast cancer and occult malignancies were evaluated.
Results:
In our institution, 925 patients were identified as BRCA mutation carriers, and 320 patients underwent contralateral RRM along with primary breast cancer surgery. BRCA2 mutation occurred more frequently (54.8%) in the overall BRCA mutation cohort. Furthermore, we reviewed 320 patients diagnosed with breast cancer and detected as BRCA mutation carriers who underwent contralateral RRM; high proportion of them were BRCA1 mutation carriers.Interestingly, we found a low incidence of only seven patients (2.2%) with occult malignancy on contralateral RRM side, which is different from that reported in other nations.
Conclusion
The incidence of occult malignancy in the contralateral breast of breast cancer patients with breast cancer with BRCA mutation is significantly low, and may be influenced by several factors. Increased utilization of screening and advancements in diagnostic technologies in South Korea have reduced the chance of occult malignancy in RRM, and a variety of pathologic examination methods may affect the rate of incidence.
9.Evaluating Rituximab Failure Rates in Neuromyelitis Optica Spectrum Disorder: A Nationwide Real-World Study From South Korea
Su-Hyun KIM ; Ju-Hong MIN ; Sung-Min KIM ; Eun-Jae LEE ; Young-Min LIM ; Ha Young SHIN ; Young Nam KWON ; Eunhee SOHN ; Sooyoung KIM ; Min Su PARK ; Tai-Seung NAM ; Byeol-A YOON ; Jong Kuk KIM ; Kyong Jin SHIN ; Yoo Hwan KIM ; Jin Myoung SEOK ; Jeong Bin BONG ; Sohyeon KIM ; Hung Youl SEOK ; Sun-Young OH ; Ohyun KWON ; Sunyoung KIM ; Sukyoon LEE ; Nam-Hee KIM ; Eun Bin CHO ; Sa-Yoon KANG ; Seong-il OH ; Jong Seok BAE ; Suk-Won AHN ; Ki Hoon KIM ; You-Ri KANG ; Woohee JU ; Seung Ho CHOO ; Yeon Hak CHUNG ; Jae-Won HYUN ; Ho Jin KIM
Journal of Clinical Neurology 2025;21(2):131-136
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.
10.The Impact of Clinical Competence and Perception of Clinical Ladder System on Organizational Commitment among Nurses at a General Tertiary Hospital
Yeon Hee SHIN ; Mi Ra LEE ; Sung Nam KIM ; Min Jung KIM ; Ae Jin KIM ; Hyun Ja KIM ; Ji Yoon KANG
Journal of Korean Academy of Nursing Administration 2025;31(1):120-131
Purpose:
This study aimed to evaluate the performance of a clinical ladder system in a tertiary hospital by examining how nurses' clinical competence and perceptions of the system affect organizational commitment.
Methods:
The study involved 394 nurses working at a tertiary hospital. Data were collected from May 3 to July 10, 2023, using a self-reported questionnaire. Statistical analyses, including descriptive statistics, independent t-tests, one-way ANOVA, Kruskal-Wallis test, Scheffé post-hoc test, Pearson correlation, and hierarchical regression analysis, were performed using SPSS 27.0.
Results:
Nurses who applied for promotion to the CN III level and current CN III nurses reported higher clinical competence, perceptions of the clinical ladder system, and organizational commitment than those who did not and those at lower levels (p<.001). A positive correlation existed among all independent variables.Controlling for general characteristics, the effects of clinical competence and perceptions of the clinical ladder system explained 49% of organizational commitment variance (Adjusted R 2 =.49, F=33.43, p<.001).
Conclusion
Greater clinical competence and positive perceptions of the clinical ladder system are likely to enhance organizational commitment, emphasizing its effectiveness in fostering better organizational outcomes.

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