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.

Objective: Multiple cohort studies have investigated the potential link between anesthesia and dementia. However, mixed findings necessitate closer examination. This study aimed to investigate the association between anesthesia exposure and the incidence of dementia, considering different anesthesia types and anesthetic agents. Methods: This nationwide cohort study utilized data from the South Korean Health Insurance Review and Assessment Service database, covering 62,541 participants, to investigate the correlation between anesthesia exposure and dementia incidence. Results: Results revealed an increased risk of dementia in individuals who underwent general (hazard ratio [HR], 1.318;95% confidence interval [CI], 1.061−1.637) or regional/local anesthesia (HR, 2.097; 95% CI, 1.887−2.329) compared to those who did not. However, combined general and regional/local anesthesia did not significantly increase dementia risk (HR, 1.097; 95% CI, 0.937−1.284). Notably, individual anesthetic agents exhibited varying risks; desflurane and midazolam showed increased risks, whereas propofol showed no significant difference. Conclusion This study provides unique insights into the nuanced relationship between anesthesia, individual anesthetic agents, and the incidence of dementia. While confirming a general association between anesthesia exposure and dementia risk, this study also emphasizes the importance of considering specific agents. These findings under-score the need for careful evaluation and long-term cognitive monitoring after anesthesia.

Background: This study aimed to investigate the prevalence, management, and comorbidities of diabetes mellitus among Korean adults. Methods: Data from the Korea National Health and Nutrition Examination Survey (2019–2022) were analyzed to assess the prevalence, treatment, risk factors, and comorbidities of diabetes. Comparisons between young and older adults with diabetes were emphasized. Results: Among Korean adults aged ≥30 years, the prevalence of diabetes is 15.5% during 2021–2022. Of these, 74.7% were aware of their condition, 70.9% received antidiabetic treatment, and only 32.4% achieved glycosylated hemoglobin (HbA1c) <6.5%. Moreover, 15.9% met the integrated management targets, which included HbA1c <6.5%, blood pressure <140/85 mm Hg, and low-density lipoprotein cholesterol <100 mg/dL. In young adults aged 19 to 39 years, the prevalence of diabetes was 2.2%. Among them, 43.3% were aware of their condition, 34.6% received treatment, and 29.6% achieved HbA1c <6.5%. Obesity affected 87.1%, and 26.9% had both hypertension and hypercholesterolemia. Among adults aged ≥65 years, the prevalence of diabetes was 29.3%, with awareness, treatment, and control rates of 78.8%, 75.7%, and 31.2%, respectively. Integrated management targets (HbA1c <7.5%, hypertension, and lipids) were achieved by 40.1%. Conclusion Diabetes mellitus remains highly prevalent among Korean adults, with significant gaps in integrated glycemic, blood pressure, and lipid control. Older adults with diabetes show higher awareness and treatment rates but limited integrated management outcomes. Young adults with diabetes bear a significant burden of obesity and comorbidities, alongside low awareness and treatment rates. Therefore, early intervention programs, education, and strategies tailored to younger populations are urgently required.

Background: Diabetes in older adults is becoming a significant public burden to South Korea. However, a comprehensive understanding of epidemiologic trends and the detailed clinical characteristics of older adults with diabetes is lacking. Therefore, we evaluated epidemiologic trends and the metabolic and lifestyle characteristics of diabetes in Korean older adults. Methods: We analyzed data from the Korea National Health and Nutrition Examination Survey to assess diabetes prevalence according to diabetes duration and lifestyle behaviors. In addition, we drew upon the National Health Information Database of the National Health Insurance System to assess physical activity levels, antidiabetic medication use, polypharmacy, medication adherence, and major comorbidities. Results: The absolute number of newly diagnosed cases of diabetes among older adults doubled over the past decade. Management rates of metabolic indicators were higher in older adults with diabetes compared to those without diabetes. The proportion of older adults with diabetes meeting the minimum recommended physical activity increased over the years. Compared to 10 years before, the use of dipeptidyl peptidase-4 inhibitor or sodium-glucose cotransporter-2 inhibitor had increased, as had comorbidities such as dyslipidemia, dementia, cancer, heart failure, atrial fibrillation, and chronic kidney disease. Initial medication adherence was significantly lower in those with end-stage kidney disease or dementia, insulin use, high-risk alcohol use, and living alone. Continuing insulin use 1 year after diagnosis of diabetes was significantly higher in those who initiated insulin therapy at diagnosis, had retinopathy, were on triple antidiabetic medications, and had a history of cancer. Conclusion Comprehensive management of metabolic indicators and physical activity is essential for older adults with diabetes. Improvements in prescribing guidelines, personalized management of age-related comorbidities, and individualized approaches that consider the heterogeneous nature of older adults with diabetes are desirable. Further research, such as high-quality cohort and intervention studies specific to older adults, is needed to establish evidence-based management for older adults with diabetes.

Background: Sarcopenia, a multifactorial disorder involving metabolic disturbance, suggests potential for metabolite biomarkers. Carnitine (CN), essential for skeletal muscle energy metabolism, may be a candidate biomarker. We investigated whether CN metabolites are biomarkers for sarcopenia. Methods: Associations between the CN metabolites identified from an animal model of sarcopenia and muscle cells and sarcopenia status were evaluated in men from an age-matched discovery (72 cases, 72 controls) and a validation (21 cases, 47 controls) cohort. Results: An association between CN metabolites and sarcopenia showed in mouse and cell studies. In the discovery cohort, plasma C5-CN levels were lower in sarcopenic men (P=0.005). C5-CN levels in men tended to be associated with handgrip strength (HGS) (P=0.098) and were significantly associated with skeletal muscle mass (P=0.003). Each standard deviation increase in C5-CN levels reduced the odds of low muscle mass (odd ratio, 0.61; 95% confidence interval [CI], 0.42 to 0.89). The area under the receiver operating characteristic curve (AUROC) of CN score using a regression equation of C5-CN levels, for sarcopenia was 0.635 (95% CI, 0.544 to 0.726). In the discovery cohort, addition of CN score to HGS significantly improved AUROC from 0.646 (95% CI, 0.575 to 0.717; HGS only) to 0.727 (95% CI, 0.643 to 0.810; P=0.006; HGS+CN score). The improvement was confirmed in the validation cohort (AUROC=0.563; 95% CI, 0.470 to 0.656 for HGS; and AUROC=0.712; 95% CI, 0.569 to 0.855 for HGS+CN score; P=0.027). Conclusion C5-CN, indicative of low muscle mass, is a potential circulating biomarker for sarcopenia in men. Further studies are required to confirm these results and explore sarcopenia-related metabolomic changes.

Alzheimer disease (AD) diagnosis is confirmed using a medley of modalities, such as the detection of amyloid-β (Aβ) neuritic plaques and neurofibrillary tangles with positron electron tomography (PET) or the appraisal of irregularities in cognitive function with examinations. Although these methods have been efficient in confirming AD pathology, the rising demand for earlier intervention during pathogenesis has led researchers to explore the diagnostic potential of fluid biomarkers in cerebrospinal fluid (CSF) and plasma. Since CSF sample collection is invasive and limited in quantity, biomarker detection in plasma has become more attractive and modern advancements in technology has permitted more efficient and accurate analysis of plasma biomolecules. In this study, we found that a composite of standard factors, Aβ40 and total tau levels in plasma, divided by the variation factor, plasma Aβ42 level, provide better correlation with amyloid neuroimaging and neuropsychological test results than a level comparison between total tau and Aβ42 in plasma. We collected EDTA-treated blood plasma samples of 53 subjects, of randomly selected 27 AD patients and 26 normal cognition (NC) individuals, who received amyloid-PET scans for plaque quantification, and measured plasma levels of Aβ40, Aβ42, and total tau with digital enzyme-linked immunosorbent assay (ELISA) in a blinded manner. There was difficulty distinguishing AD patients from controls when analyzing biomarkers independently. However, significant differentiation was observed between the two groups when comparing individual ratios of total-tau×Aβ40/Aβ42. Our results indicate that collectively comparing fluctuations of these fluid biomarkers could aid in monitoring AD pathogenesis.

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: Since 1995, the Korean Gastric Cancer Association (KGCA) has been periodically conducting nationwide surveys on patients with surgically treated gastric cancer. This study details the results of the survey conducted in 2023. Materials and Methods: The survey was conducted from March to December 2024 using a standardized case report form. Data were collected on 86 items, including patient demographics, tumor characteristics, surgical procedures, and surgical outcomes. The results of the 2023 survey were compared with those of previous surveys. Results: Data from 12,751 cases were collected from 66 institutions. The mean patient age was 64.6 years, and the proportion of patients aged ≥71 years increased from 9.1% in 1995 to 31.7% in 2023. The proportion of upper-third tumors slightly decreased to 16.8% compared to 20.9% in 2019. Early gastric cancer accounted for 63.1% of cases in 2023.Regarding operative procedures, a totally laparoscopic approach was most frequently applied (63.2%) in 2023, while robotic gastrectomy steadily increased to 9.5% from 2.1% in 2014.The most common anastomotic method was the Billroth II procedure (48.8%) after distal gastrectomy and double-tract reconstruction (51.9%) after proximal gastrectomy in 2023.However, the proportion of esophago-gastrostomy with anti-reflux procedures increased to 30.9%. The rates of post-operative mortality and overall complications were 1.0% and 15.3%, respectively. Conclusions The results of the 2023 nationwide survey demonstrate the current status of gastric cancer treatment in Korea. This information will provide a basis for future gastric cancer research.