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: This study aimed to identify the risk factors for chronic kidney disease (CKD) and end-stage renal disease (ESRD) following liver transplantation (LT), with a specific focus on tacrolimus levels and intrapatient variability (IPV). Methods: Among the 1,076 patients who underwent LT between 2000 and 2018, 952 were included in the analysis. The tacrolimus doses and levels were recorded every 3 months, and the IPV was calculated using the coefficient of variability. The cumulative incidence rates of CKD and ESRD were calculated based on baseline kidney function at the time of LT. The impact of tacrolimus levels and their IPV on the development of CKD and ESRD was evaluated, and the significant risk factors were identified. Results: Within a median follow-up of 97.3 months, the 5-year cumulative incidence rates of CKD (0.58 vs. 0.24) and ESRD (0.07 vs. 0.01) were significantly higher in the acute kidney injury group than in the normal glomerular filtration rate (GFR) group. In the normal GFR group, the tacrolimus levels were identified as a risk factor for CKD, with a level of ≤4.5 ng/mL suggested as optimal for minimizing the risk of CKD. Furthermore, the IPV of tacrolimus levels and doses emerged as a significant risk factor for CKD development in both groups (p<0.05), with tenofovir disoproxil fumarate also being a risk factor in HBV-infected patients. The IPV of tacrolimus levels was also a significant factor in ESRD development (p<0.05). Conclusions This study elucidated the optimal tacrolimus trough level and highlighted the impact of IPV on the CKD and ESRD development post-LT.

Objective: This study investigated how educational levels modify the relationship between the standard deviation of NN intervals (SDNN) of heart rate variability and the development of post-traumatic stress disorder (PTSD). Methods: Participants with physical injuries were enrolled from a trauma center and monitored over two years. Initial assessments included SDNN and educational attainment, along with socio-demographic and clinical variables. PTSD diagnoses were made at 3, 6, 12, and 24 months post-injury using the Clinician-Administered PTSD Scale for DSM-5.Logistic regression analyses were conducted. Results: Of the 538 participants, 58 (10.8%) developed PTSD during the follow-up period. A significant interaction effect was observed: lower SDNN was significantly linked to PTSD in individuals with higher education, but not in those with lower education. Conclusion The study identified education-dependent associations between SDNN and PTSD development, emphasizing the importance of tailored PTSD prevention strategies that consider both SDNN and educational levels.

Background: This study aimed to investigate changes in gene expression related to matrix synthesis in individuals with fullthickness rotator cuff tears (RCTs) and normal tendon tissues. The study also aimed to examine the differences in gene expression according to 4 distinct tear sizes. Methods: A total of 12 patients with full-thickness RCTs were included in the study, all of whom underwent arthroscopic rotator cuff repair. The RCTs were stratified by size into small, medium, large, and massive. Tendon samples were harvested from the midpoint between the lateral end of the torn tendon and the musculotendinous junction. Subsequent analysis of the tissue samples revealed the mRNA expression levels of 11 collagen types, 6 proteoglycans, and 8 glycoproteins through real-time polymerase chain reaction techniques. For control purposes, supraspinatus tendon tissue was sourced from 3 patients who had proximal humerus fractures but did not present with RCTs. Results: Among the 11 collagens and 14 non-collagenous protein (NCP) genes examined in this study, COL3A1 and COL10A1 showed a significant increase, whereas COL4A1 and COL14A1 showed a tendency to decrease compared to those in the normal group. ACAN significantly increased by 8.92-fold (p < 0.001) compared to that in the normal group, whereas DCN and LUM showed a tendency to decrease. FN1 and TNC increased significantly by 3.47-fold (p = 0.003) and 5.38-fold (p = 0.005), respectively, and the genes ELN, LAMA2, and THBS1 were all significantly reduced compared to those in the normal group. In the NCPs, almost all the genes with increased expression levels had the highest level in small size RCTs, and gene expression decreased as the size increased. The 3 proteoglycans (ACAN, BGN, and FMOD) showed the highest levels of expression in small size RCTs compared to those in the normal group, and 5 glycoproteins (COMP, FBN1, FN1, HAPLN1, and TNC) also showed the highest expression in small size RCTs. Conclusions We confirmed that most of the detected extracellular matrix gene expression changes were related to the size of the full-thickness RCTs. In NCPs, gene expression was increased in small-size tears, and gene expression levels were significantly reduced when the size increased.

Background: and Purpose: This clinical practice guideline provides evidence-based recommendations for treatment of dementia, focusing on cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists for Alzheimer’s disease (AD) and other types of dementia. Methods: Using the Population, Intervention, Comparison, Outcomes (PICO) framework, we developed key clinical questions and conducted systematic literature reviews. A multidisciplinary panel of experts, organized by the Korean Dementia Association, evaluated randomized controlled trials and observational studies. Recommendations were graded for evidence quality and strength using Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. Results: Three main recommendations are presented: (1) For AD, cholinesterase inhibitors (donepezil, rivastigmine, galantamine) are strongly recommended for improving cognition and daily function based on moderate evidence; (2) Cholinesterase inhibitors are conditionally recommended for vascular dementia and Parkinson’s disease dementia, with a strong recommendation for Lewy body dementia; (3) For moderate to severe AD, NMDA receptor antagonist (memantine) is strongly recommended, demonstrating significant cognitive and functional improvements. Both drug classes showed favorable safety profiles with manageable side effects. Conclusions This guideline offers standardized, evidence-based pharmacologic recommendations for dementia management, with specific guidance on cholinesterase inhibitors and NMDA receptor antagonists. It aims to support clinical decision-making and improve patient outcomes in dementia care. Further updates will address emerging treatments, including amyloid-targeting therapies, to reflect advances in dementia management.

Background: Gestational diabetes mellitus (GDM) affects women with diverse pathological phenotypes, but little is known about the effects of this variation on perinatal outcomes. We explored the metabolic phenotypes of GDM and their impact on adverse pregnancy outcomes. Methods: Women diagnosed with gestational glucose intolerance or GDM were categorized into subgroups according to their prepregnancy body mass index (BMI) and the median values of the gestational Matsuda and Stumvoll indices. Logistic regression analysis was employed to assess the odds of adverse pregnancy outcomes, such as large-for-gestational age (LGA), small-for-gestational age, preterm birth, low Apgar score, and cesarean section. Results: A total of 309 women were included, with a median age of 31 years and a median BMI of 22.3 kg/m2. Women with a higher pre-pregnancy BMI had a higher risk of LGA newborns (adjusted odds ratio [aOR] for pre-pregnancy BMI ≥25 kg/m2 compared to 20–23 kg/m2, 4.26; 95% confidence interval [CI], 1.99 to 9.12; P<0.001; P for trend=0.001), but the risk of other adverse pregnancy outcomes did not differ according to pre-pregnancy BMI. Women with insulin resistance had a higher risk of LGA (aOR, 1.88; 95% CI, 1.02 to 3.47; P=0.043) and cesarean section (aOR, 2.12; 95% CI, 1.29 to 3.50; P=0.003) than women in the insulin-sensitive group. In contrast, defective β-cell function did not affect adverse pregnancy outcomes. Conclusion Different metabolic phenotypes of GDM were associated with heterogeneous pregnancy outcomes. Women with obesity and those with insulin resistance are at greater risk of adverse outcomes and might need strict glycemic management during pregnancy.

Background/Aims: We previously reported that patients with moderate-to-severe ulcerative colitis (UC) often experience common mental disorders (CMDs) such as anxiety and depression, necessitating immediate psychological interventions within the first 4 weeks of diagnosis. In this 3-year follow-up study of the MOSAIK cohort in Korea, we examined the effects of CMDs at initial diagnosis on clinical outcomes and health-related quality of life (HRQoL). Methods: We examined differences in clinical outcomes (evaluated based on clinical response, relapse, hospitalization, and medication use) and HRQoL (assessed using the Inflammatory Bowel Disease Questionnaire [IBDQ] and Short Form 12 [SF-12]) according to Hospital Anxiety and Depression Scale (HADS) scores at diagnosis. Results: In a study involving 199 UC patients, 47.7% exhibited significant psychological distress (anxiety and/or depression) at diagnosis. Clinical follow-up showed no major differences in outcomes, including remission rates, response rates, or hospitalization rates, between patients with anxiety or depression at diagnosis and patients without anxiety or depression at diagnosis. The HRQoL at the end of follow-up was notably lower in those with baseline CMDs, particularly anxiety, across all domains of the IBDQ and SF-12. Linear mixed-effect models revealed that higher HADS scores, as well as higher Mayo scores, were independently associated with lower IBDQ scores and both summary domains of the SF-12. Additionally, regular attendance at follow-up visits during the study period was also related to improvements in HRQoL (all p<0.05). Conclusions While CMDs present at the time of UC diagnosis did not influence long-term clinical outcomes, they persistently impaired HRQoL. Our findings support the routine incorporation of psychological interventions into the long-term management of moderate-to-severe UC.

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.

Background: Immunocompromised patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection often have prolonged viral shedding, and some are clinically suspected of reinfection with different SARSCoV-2 variants. However, data on this issue are limited. This study investigated the SARS-CoV-2 variants in serially collected respiratory samples from immunocompromised patients with prolonged viral shedding for over 12 weeks or relapsed viral shedding after at least 2 weeks of viral clearance. Materials and Methods: From February 2022 to September 2023, we prospectively enrolled immunocompromised patients with coronavirus disease 2019 who had hematologic malignancies or had undergone transplantation and were admitted to a tertiary hospital. Weekly saliva or nasopharyngeal swabs were collected from enrolled patients for at least 12 weeks after diagnosis. Genomic RNA polymerase chain reaction (PCR) was performed on samples, and those testing positive underwent viral culture to isolate the live virus. Spike gene full sequencing via Sanger sequencing and real-time reverse transcription-PCR for detecting mutation genes were conducted to identify SARSCoV-2 variants. Results: Among 116 enrolled patients, 20 with prolonged or relapsed viral shedding were screened to identify the variants. Of these 20 patients, 7 (35%) exhibited evidence of re-infection; one of 8 patients with prolonged viral shedding and 6 of 12 with relapsed viral shedding were reinfected with SARS-CoV-2. Conclusion Our data suggest that approximately one-third of immunocompromised patients with persistent or relapsed viral shedding had reinfection with different variants of SARS-CoV-2.