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.

Alzheimer’s disease (AD), a neurodegenerative disorder characterized by the accumulation of amyloid-beta plaques and tau tangles, shows cognitive decline. Recent genetic studies have identified over 30 variants that are resilient to AD pathology, offering new therapeutic opportunities. This review explores key protective mutations of APOE3 Christchurch, RELNCOLBOS, FN1, APP A673T, BDNF Val66Met, SORL1, CR1, TREM2, PICALM, and INPP5 D genes.These affect critical pathways, including lipid metabolism, synaptic function, tau regulation, and immune response. Potential treatments are discussed, including gene therapy and neuroprotective strategies, emphasizing a shift toward precision medicine focused on genetic resilience. By reviewing case studies and relevant literatures, the work explores the mechanisms by which these variants mitigate amyloid accumulation, tau pathology, neurodegeneration, and neuroinflammation, the key contributors to AD progression. Understanding these protective pathways offers critical insights into potential therapeutic applications, such as gene therapy, immune-modulating treatments, and personalized medicine approaches tailored to the individual’s genetic profile. The findings highlight the potential to leverage genetic protection mechanisms to develop precision interventions for AD, offering new hope to prevent or delay disease onset and progression. These discoveries could transform future treatment strategies, shifting the focus from risk management to exploiting genetic resilience to combat AD.

Background: The novel sodium-glucose cotransporter-2 (SGLT2) inhibitor enavogliflozin effectively lowers glycosylated hemoglobin levels and body weights without the increased risk of serious adverse events; however, the long-term clinical benefits of enavogliflozin in terms of cardiovascular and renal outcomes have not been investigated. Methods: This study is an investigator-initiated, multicenter, randomized, pragmatic, open-label, active-controlled, non-inferiority trial. Eligible participants are adults (aged ≥19 years) with type 2 diabetes mellitus (T2DM) who have a history of, or are at risk of, cardiovascular disease. A total of 2,862 participants will be randomly assigned to receive either enavogliflozin or other SGLT2 inhibitors with proven cardiorenal benefits, such as dapagliflozin or empagliflozin. The primary endpoint is the time to the first occurrence of a composite of major adverse cardiovascular or renal events (Clinical Research Information Service registration number: KCT0009243). Conclusion This trial will determine whether enavogliflozin is non-inferior to dapagliflozin or empagliflozin in terms of cardiorenal outcomes in patients with T2DM and cardiovascular risk factors. This study will elucidate the role of enavogliflozin in preventing vascular complications in patients with T2DM.

Background: Active surveillance (AS) has emerged as a viable management strategy for low-risk papillary thyroid microcarcinoma (PTMC), following pioneering trials at Kuma Hospital and the Cancer Institute Hospital in Japan. Numerous prospective cohort studies have since validated AS as a management option for low-risk PTMC, leading to its inclusion in thyroid cancer guidelines across various countries. From 2016 to 2020, the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Microcarcinoma (MAeSTro) enrolled 1,177 patients, providing comprehensive data on PTMC progression, sonographic predictors of progression, quality of life, surgical outcomes, and cost-effectiveness when comparing AS to immediate surgery. The second phase of MAeSTro (MAeSTro-EXP) expands AS to low-risk papillary thyroid carcinoma (PTC) tumors larger than 1 cm, driven by the hypothesis that overall risk assessment outweighs absolute tumor size in surgical decision-making. Methods: This protocol aims to address whether limiting AS to tumors smaller than 1 cm may result in unnecessary surgeries for low-risk PTCs detected during their rapid initial growth phase. By expanding the AS criteria to include tumors up to 1.5 cm, while simultaneously refining and standardizing the criteria for risk assessment and disease progression, we aim to minimize overtreatment and maintain rigorous monitoring to improve patient outcomes. Conclusion This study will contribute to optimizing AS guidelines and enhance our understanding of the natural course and appropriate management of low-risk PTCs. Additionally, MAeSTro-EXP involves a multinational collaboration between South Korea and Australia. This cross-country study aims to identify cultural and racial differences in the management of low-risk PTC, thereby enriching the global understanding of AS practices and their applicability across diverse populations.

Background/Aims: Findings on the impact of Helicobacter pylori eradication on metabolic parameters are inconsistent. This study aimed to evaluate the effects of H. pylori eradication on metabolic parameters and body composition, including body fat mass and skeletal muscle mass. Methods: We retrospectively reviewed the data of asymptomatic patients who underwent health screenings, including bioelectrical impedance analysis, before and after H. pylori eradication between 2005 and 2021. After matching individuals based on key factors, we compared lipid profiles, metabolic parameters, and body composition between 823 patients from the eradicated group and 823 patients from the non-eradicated groups. Results: Blood pressure, erythrocyte sedimentation rate, and glycated hemoglobin values were significantly lower in the eradicated group than in the non-eradicated group. However, changes in body mass index (BMI), body fat mass, appendicular skeletal muscle mass (ASM), waist circumference, and lipid profiles were not significantly different between the two groups. In a subgroup analysis of individuals aged >45 years, blood pressure, erythrocyte sedimentation rate, and glycated hemoglobin changes were significantly lower in the eradicated group than in the noneradicated group. BMI values were significantly higher in the eradicated group than in the noneradicated group; however, no significant differences were observed between the two groups regarding changes in body weight, body fat mass, ASM, or waist circumference. Total cholesterol and low-density lipoprotein cholesterol levels were significantly lower in the eradicated group than in non-eradicated group. Conclusions H. pylori eradication significantly reduced blood pressure, glucose levels, and systemic inflammation and improved lipid profiles in patients aged >45 years. BMI, body fat mass, ASM, and waist circumference did not significantly differ between patients in the eradicated group and those in the non-eradicated group.

Background/Aims: The study investigated the incidence, risk factors, and clinical outcomes of chronic antibiotic-refractory pouchitis (CARP) in Korean patients with ulcerative colitis (UC). Methods: This single-center retrospective study included patients with UC who underwent total proctocolectomy with ileal pouch-anal anastomosis at the Asan Medical Center in Korea between January 1987 and December 2022. The primary outcomes were endoscopic remission and pouch failure. The Cox’s proportional hazard model was used to identify the risk factors for CARP. Results: The clinical data of 232 patients were analyzed. The most common cause of surgery was steroid refractoriness (50.9%), followed by dysplasia/colorectal cancer (26.7%). Among 74 patients (31.9%) with chronic pouchitis (CP), 31 (13.4%) had CARP, and 43 (18.5%) had chronic antibiotic-dependent pouchitis (CADP). The most frequent endoscopic phenotype was focal inflammation of the pouch (CP, 47.3%; CARP, 35.5%; CADP, 55.8%). Patients with CARP were less likely to use concomitant probiotics than patients with CADP (29.0% vs 72.1%, p<0.01). The endoscopic remission rate of CP, CARP, and CADP was 14.9%, 9.7%, and 18.6%, respectively.The pouch failure rate associated with CP, CARP, and CADP was 13.5%, 16.1%, and 11.6%, respectively. Current smoking status (adjusted hazard ratio [aHR], 2.96; 95% confidence interval [CI], 1.27 to 6.90; p=0.01) and previous use of biologics/small molecules (aHR, 2.40; 95% CI, 1.05 to 5.53; p=0.04) were significantly associated with CARP development. Conclusions UC patients who were current smokers and previously used biologics/small molecules had a higher risk of developing CARP. Concomitant use of probiotics was less likely to be associated with CARP development.

Background: The World Health Organization has declared the end of the coronavirus disease 2019 (COVID-19) public health emergency. However, this did not indicate the end of COVID-19. Several months after the infection, numerous patients complain of respiratory or nonspecific symptoms; this condition is called long COVID. Even patients with mild COVID-19 can experience long COVID, thus the burden of long COVID remains considerable. Therefore, we conducted this study to comprehensively analyze the effects of long COVID using multi-faceted assessments. Materials and Methods: We conducted a prospective cohort study involving patients diagnosed with COVID-19 between February 2020 and September 2021 in six tertiary hospitals in Korea. Patients were followed up at 1, 3, 6, 12, 18, and 24 months after discharge. Long COVID was defined as the persistence of three or more COVID-19-related symptoms. The primary outcome of this study was the prevalence of long COVID after the period of COVID-19. Results: During the study period, 290 patients were enrolled. Among them, 54.5 and 34.6% experienced long COVID within 6 months and after more than 18 months, respectively. Several patients showed abnormal results when tested for post-traumatic stress disorder (17.4%) and anxiety (31.9%) after 18 months. In patients who underwent follow-up chest computed tomography 18 months after COVID-19, abnormal findings remained at 51.9%. Males (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.05–0.53; P=0.004) and elderly (OR, 1.04; 95% CI, 1.00–1.09; P=0.04) showed a significant association with long COVID after 12–18 months in a multivariable logistic regression analysis. Conclusion Many patients still showed long COVID after 18 months post SARS-CoV-2 infection. When managing these patients, the assessment of multiple aspects is necessary.

Pneumocystis jirovecii pneumonia (PJP) is a life-threatening infection commonly observed in immunocompromised patients, necessitating prompt diagnosis and treatment. This review evaluates the diagnostic performance of various tests used for PJP diagnosis through a comprehensive literature review. Additionally, we propose a diagnostic algorithm tailored to non-human immunodeficiency virus immunocompromised patients, considering the specific characteristics of current medical resources in Korea.

Purpose: This study investigated urinary incontinence (UI) following holmium laser enucleation of the prostate (HoLEP), based on the postoperative period, type of UI, and severity according to prostate volume. Methods: We analyzed prospectively collected data from patients who underwent HoLEP for benign prostatic hyperplasia at Seoul National University Hospital between January 2010 and June 2022. Patients were followed-up at 2 weeks, 3 months, and 6 months postoperatively. The patients were divided into 3 prostate volume groups: A (30–80 mL), B (81–120 mL), and C (>120 mL). We compared clinical outcomes and UI rates between the groups. Results: In total, 1,675 patients were included. The preoperative urgency UI (UUI) rate was 16.1%, with no significant difference between the groups (P=0.81). Two weeks postoperatively, the UUI rate was 6.0% (including a de novo UUI rate of 4.2%), with no significant differences between the groups. The stress UI (SUI) rate at 2 weeks postoperatively was 6.3%, and increased with larger prostate volume (P=0.04). The UUI and SUI rates decreased to 0.9% and 1.2%, respectively, 6 months postoperatively. Six months postoperatively, the SUI rate was significantly lower in group A (P=0.02), whereas the UUI rate did not differ between the groups (P=0.69). Conclusions Our results demonstrated that the preoperative UUI rate was high at baseline. Both the UUI and SUI rates continuously decreased up to 6 months postoperatively. Although the SUI rates significantly differed according to prostate volume, there was no significant difference in the UUI rate.

Purpose: This study analyzed the pathological complete response (pCR) rates, long-term outcomes, and biological features of human epidermal growth factor receptor 2 (HER2)-zero, HER2-low, and HER2-positive breast cancer patients undergoing neoadjuvant treatment. Methods: This single-center study included 1,667 patients who underwent neoadjuvant chemotherapy from 2008 to 2014. Patients were categorized by HER2 status, and their clinicopathological characteristics, chemotherapy responses, and recurrence-free survival (RFS) rates were analyzed. Results: Patients with HER2-low tumors were more likely to be older (p = 0.081), have a lower histological grade (p < 0.001), and have hormone receptor (HorR)-positive tumors (p < 0.001). The HER2-positive group exhibited the highest pCR rate (23.3%), followed by the HER2-zero (15.5%) and HER2-low (10.9%) groups. However, the pCR rate did not differ between HER2-low and HER2-zero tumors in the HorR-positive or HorR-negative subgroups.The 5-year RFS rates increased in the following order: HER2-low, HER2-positive, and HER2-zero (80.0%, 77.5%, and 74.5%, respectively) (log-rank test p = 0.017). A significant survival difference between patients with HER2-low and HER2-zero tumors was only identified in HorR-negative tumors (5-year RFS for HER2-low, 74.5% vs. HER2-zero, 66.0%; log-rank test p-value = 0.04). Multivariate survival analysis revealed that achieving a pCR was the most significant factor associated with improved survival (hazard ratio [HR], 4.279; p < 0.001).Compared with HER2-zero, the HRs for HER2-low and HER2-positive tumors were 0.787 (p = 0.042) and 0.728 (p = 0.005), respectively. After excluding patients who received HER2-targeted therapy, patients with HER2-low tumors exhibited better RFS than those with HER2-zero (HR 0.784, p = 0.04), whereas those with HER2-positive tumors exhibited no significant difference compared with those with HER2-low tumors (HR, 0.975; p = 0.953). Conclusion Patients with HER2-low tumors had no significant difference in pCR rate compared to HER2-zero but showed better survival, especially in HorR-negative tumors.Further investigation into biological differences is warranted.