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.

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.

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.

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.

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.

Echinococcosis, caused by the tapeworm Echinococcus, is rare in Korea and is primarily imported from endemic areas. We report a case of a 37-year-old Korean man with multiple large hepatic cysts, initially diagnosed as simple cysts at a local clinic in 2018. The patient had lived in Oman, an endemic area, for several months in 2016. Upon referral to a tertiary hospital in 2023, due to progressive cyst enlargement, liver magnetic resonance imaging revealed three large cysts with a water lily sign. Serum IgG against Echinococcus was positive by enzyme-linked immunosorbent assay. After diagnosis of echinococcosis, treatment with albendazole and puncture-aspiration-injection-reaspiration (PAIR) was performed.Microscopic and molecular analysis of cyst aspirates confirmed Echinococcus granulosus infection. Follow-up computed tomography demonstrated a reduction in cyst size, yet the emergence of a new right pleural effusion and consolidation in the left lower lobe of the lung necessitated the continuation of albendazole therapy. This case highlights the importance of thorough travel history, imaging findings, and the effectiveness of PAIR combined with albendazole in treating imported echinococcosis.

Background: We evaluated severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2)-specific humoral and cellular responses for up to 6 months after the 3rd dose of ancestral coronavirus disease 2019 (COVID-19) vaccination in people living with HIV (PLWH) and healthy controls (HCs) who were not infected with COVID-19. Methods: Anti-spike receptor-binding domain IgG (anti-RBD IgG) concentrations using chemiluminescence immunoassay and neutralizing antibodies using focus reduction neutralization test (FRNT) were assessed at 1 week after each dose of vaccination, and 3 and 6 months after the 3rd dose in 62 PLWH and 25 HCs. T-cell responses using intracellular cytokine stain were evaluated at 1 week before, and 1 week and 6 months after the 3rd dose. Results: At 1 week after the 3rd dose, adequate anti-RBD IgG (> 300 binding antibody unit /mL) was elicited in all PLWH except for one patient with 36 CD4 T-cell count/mm3 . The geometric mean titers of 50% FRNT against wild type (WT) and omicron BA.5 strains of SARS-CoV-2 in PLWH with CD4 T-cell count ≥ 500 cells/mm3(high CD4 recovery, HCDR) were comparable to HC, but they were significantly decreased in PLWH with CD4 T-cell count < 500/mm3 (low CD4 recovery, LCDR). After adjusting for age, gender, viral suppression, and number of preexisting comorbidities, CD4 T-cell counts < 500/mm3 significantly predicted a poor magnitude of neutralizing antibodies against WT, omicron BA.5, and XBB 1.5 strains among PLWH. Multivariable linear regression adjusting for age and gender revealed that LCDR was associated with reduced neutralizing activity (P = 0.017) and interferon-γ-producing T-cell responses (P = 0.049 for CD T-cell; P = 0.014 for CD8 T-cell) against WT, and strongly associated with more decreased cross-neutralization against omicron BA.5 strains (P < 0.001). Conclusion HCDR demonstrated robust humoral and cell-mediated immune responses after a booster dose of ancestral SARS-CoV-2 vaccine, whereas LCDR showed diminished immune responses against WT virus and more impaired cross-neutralization against omicron BA.5 strain.

Objective: Although high-density lipoprotein cholesterol (HDL-C) is inversely associated with hematologic malignancies, modification by smoking has not been reported. We investigated how smoking and menopausal status modify these association. Methods: This population-based cohort study enrolled cancer-free individuals who underwent a national cancer screening in 2010 and followed up until December 2017. HDL-C levels were classified into eight groups based on 10 mg/dL intervals: (<30, 30–39, 40–49, 50–59, 60–69, 70–79, 80–89, or ≥90 mg/dL). Results: Among 4,517,892 participants, 5887 had lymphoma, 3348 had leukemia, and 12151 had unspecified hematologic malignancies. The adjusted hazard ratios (aHRs) for the lowest HDL-C levels compared to the 70–79 mg/dL range were 1.83 (1.45–2.31) for lymphoma, 3.14 (2.41–4.08) for leukemia, and 2.34 (2.01–2.72) for unspecified hematologic malignancy.The effects of low HDL-C levels on hematologic malignancies were similar in both men and women. Low HDL-C levels were associated with a higher risk of leukemia regardless of smoking status, but extremely high HDL-C levels were linked to a higher risk of leukemia (aHR, 2.32; 95% confidence interval [95% CI], 1.18–4.55) only in current smokers.The hazardous effect of low HDL-C levels on lymphoma was significant only in never smokers (aHR, 2.01; 95% CI, 1.51–2.68). Hazardous effects of low HDL-C levels on leukemia were observed only in post-menopausal women (aHR, 2.94; 95% CI, 1.69–5.11). Conclusion Low HDL-C levels were associated with a higher risk of leukemia and lymphoma, with discrepancies based on smoking and menopausal status.

Background: Complete revascularization has demonstrated better outcomes in patients with acute myocardial infarction (AMI) and multivessel disease. However, in the case of left main (LM) culprit lesion AMI with multivessel disease, there is limited evidence to suggest that complete revascularization is better. Methods: We reviewed 16,831 patients in the Korea Acute Myocardial Infarction Registry who were treated from July 2016 to June 2020, and 399 patients were enrolled with LM culprit lesion AMI treated with percutaneous coronary intervention. We categorized the patients as those treated with complete revascularization (n=295) or incomplete revascularization (n=104). The study endpoint was major adverse cardiac and cerebrovascular events (MACCE), a composite of all-cause death, myocardial infarction, ischemia-driven revascularization, stent thrombosis, and stroke. We performed propensity score matching (PSM) and analyzed the incidence of MACCE at 1 year. Results: After PSM, the two groups were well balanced. There was no significant difference between the two groups in MACCE at 1 year (12.1% vs. 15.2%; hazard ratio, 1.28; 95% confidence interval, 0.60–2.74; p=0.524) after PSM. The components of MACCE and major bleeding were also not significantly different. Conclusion There was no significant difference in clinical outcomes between the groups treated with complete or incomplete revascularization for LM culprit lesion AMI with multivessel disease.

Ketone bodies produced by sodium-glucose cotransporter 2 (SGLT2) inhibitors can be advantageous, providing an efficient and stable energy source for the brain and muscles. However, in patients with diabetes, ketogenesis induced by SGLT2 inhibitors may be harmful, potentially resulting in severe diabetic ketoacidosis (DKA). During fasting, ketone body production serves as an alternative and efficient energy source for the brain by utilizing stored fat, promoting mental clarity, and reducing dependence on glucose. The concurrent use of SGLT2 inhibitors during perioperative fasting may further elevate the risk of euglycemic DKA. We describe a case of DKA that occurred during perioperative fasting in a patient receiving empagliflozin, an SGLT2 inhibitor. This case underscores the importance of recognizing the potential risk of DKA in patients with diabetes using SGLT2 inhibitors during perioperative fasting.