Reported Adverse Events and Associated Factors in Korean Coronavirus Disease 2019 Vaccinations.

BACKGROUND: Despite their effectiveness, coronavirus disease 2019 (COVID-19) vaccines have been associated with adverse effects, underscoring the importance of continuous surveillance to ensure vaccine safety and effective management of public health. Herein, the characteristics and risk factors of vaccine-related adverse events (AEs) were identified to gain an in-depth understanding of vaccine safety by investigating the impact of the vaccination dose on changes in post-vaccination AEs. METHODS: Herein, a linked database of COVID-19 vaccination records from the Korea Disease Control and Prevention Agency, AE reports from the COVID-19 Vaccination Management System, and healthcare claims from the National Health Insurance Service, targeting ≥ 5-year-old individuals, was utilized (study duration = February 26, 2021, to January 31, 2023). The frequency and severity of reported post-vaccination AEs were evaluated. Furthermore, we specifically explored AEs in relation to the cumulative dosage of vaccines administered while evaluating associated risk factors. RESULTS: During the observation period, 42,804,523 individuals completed the COVID-19 vaccination series, with 365,900 reporting AEs, with headache, muscle pain, and fever being the most frequently reported. Notably, the AE reports were approximately twice as high for women than for men, which was further exacerbated following both doses. Analysis by age group revealed that AE reports were lower among children, adolescents, and older adults than in the middle-aged cohort (age = 50-64 years), with higher reports observed for 18-49-year-old individuals. Additionally, a higher risk of reporting was identified among individuals with lower socioeconomic status compared with those of middle socioeconomic status. Excluding dementia, the risk of reporting AEs was high in individuals with underlying diseases compared with those without, for instance, the risk of reporting AEs following two-dose vaccinations was approximately twice as high in individuals with chronic obstructive pulmonary disease and asthma. CONCLUSION: These findings indicate that women, younger people, those with a lower socioeconomic status, and those with underlying health conditions reported a higher incidence of AEs following COVID-19 vaccinations. This emphasizes the need for continued monitoring to ensure safe vaccination and address vaccine-related anxiety and fear, especially within the aforementioned groups.

Image Quality and Lesion Detectability of Low-Concentration Iodine Contrast and Low Radiation Hepatic Multiphase CT Using a Deep-Learning-Based Contrast-Boosting Model in Chronic Liver Disease Patients.

BACKGROUND: This study investigated the image quality and detectability of double low-dose hepatic multiphase CT (DLDCT, which targeted about 30% reductions of both the radiation and iodine concentration) using a vendor-agnostic deep-learning-based contrast-boosting model (DL-CB) compared to those of standard-dose CT (SDCT) using hybrid iterative reconstruction. METHODS: The CT images of 73 patients with chronic liver disease who underwent DLDCT between June 2023 and October 2023 and had SDCT were analyzed. Qualitative analysis of the overall image quality, artificial sensation, and liver contour sharpness on the arterial and portal phase, along with the hepatic artery clarity was conducted by two radiologists using a 5-point scale. For quantitative analysis, the image noise, signal-to-noise ratio, and contrast-to-noise ratio were measured. The lesion conspicuity was analyzed using generalized estimating equation analysis. Lesion detection was evaluated using the jackknife free-response receiver operating characteristic figures-of-merit. RESULTS: Compared with SDCT, a significantly lower effective dose (16.4 ± 7.2 mSv vs. 10.4 ± 6.0 mSv, 36.6% reduction) and iodine amount (350 mg iodine/mL vs. 270 mg iodine/mL, 22.9% reduction) were utilized in DLDCT. The mean overall arterial and portal phase image quality scores of DLDCT were significantly higher than SDCT (arterial phase, 4.77 ± 0.45 vs. 4.93 ± 0.24, AUCVGA 0.572 [95% CI, 0.507-0.638]; portal phase, 4.83 ± 0.38 vs. 4.92 ± 0.26, AUCVGA 0.535 [95% CI, 0.469-0.601]). Furthermore, DLDCT showed significantly superior quantitative results for the lesion contrast-to-noise ratio (7.55 ± 4.55 vs. 3.70 ± 2.64, p < 0.001) and lesion detectability (0.97 vs. 0.86, p = 0.003). CONCLUSIONS: In patients with chronic liver disease, DLDCT using DL-CB can provide acceptable image quality without impairing the detection and evaluation of hepatic focal lesions compared to SDCT.

Clinical characteristics of seizure recurrence and epilepsy development in patients with alcohol-related seizures.

BACKGROUND: Alcohol withdrawal is widely recognized as a trigger for acute symptomatic seizures among individuals with chronic alcohol consumption. While most alcohol withdrawal seizures occur shortly after cessation, chronic alcohol consumption can be associated with the development of epilepsy, necessitating anti-epileptic drug (AED) therapy. This study aimed to investigate the clinical characteristics, seizure recurrence, and epilepsy development in patients with alcohol-related seizures and to identify prognostic factors for epilepsy. METHODS: In a retrospective analysis at Ewha Womans University Mokdong Hospital, 206 patients with alcohol-related seizures were examined and 15 were excluded due to preexisting epilepsy. Demographic and clinical data, including alcohol withdrawal duration, seizure recurrence, types, and comorbidities, were investigated. Logistic regression models were used to analyze the risk factors for seizure recurrence and epilepsy development. The performance of the final models was evaluated based on the area under the receiver operating characteristic curve (AUC) and validated using calibration plots and leave-one-out cross-validation. RESULTS: Of the 191 patients (146 males; mean age 48.3 ± 12.1 years) with alcohol-related seizures, 99 patients (51.8%) experienced seizure recurrence and 79 patients (41.4%) developed epilepsy. Factors associated with seizure recurrence included alcohol consumption levels, occurrence of focal impaired awareness seizure, anxiety, and headache. The number of recurrent seizures, semiology, status epilepticus, electroencephalogram findings, and brain imaging findings was associated with epilepsy development. The predictive models showed strong diagnostic performance, with AUCs of 0.833 for seizure recurrence and 0.939 for epilepsy development. CONCLUSION: High alcohol consumption and specific clinical and diagnostic features are significant predictors of seizure recurrence and the development of epilepsy among patients with alcohol-related seizures. These findings underscore the importance of early identification and intervention to prevent seizure recurrence and the onset of epilepsy, emphasizing the importance of AED treatment in managing these conditions.

Effects of Intermittent Calorie Restriction in Nondiabetic Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease.

BACKGROUND & AIMS: We compared the effects of a 12-week intermittent calorie restriction (ICR) and standard-of-care (SOC) diet on liver fat content (LFC) in metabolic dysfunction-associated steatotic liver disease patients. METHODS: This randomized controlled trial included patients with magnetic resonance imaging-proton density fat fraction ≥8%. Patients were randomly assigned to the ICR (5:2 diet) or SOC (80% of the recommended calorie intake) groups and stratified according to the body mass index (≥25 or <25 kg/m2). The primary outcome was the proportion of patients who achieved a relative LFC reduction as measured by magnetic resonance imaging-proton density fat fraction ≥30%. RESULTS: Seventy-two participants underwent randomization (36 patients with and 36 without obesity), and 63 (34 patients with and 29 without obesity) completed the trial. At week 12, a higher proportion of patients in the ICR arm achieved a relative LFC reduction of ≥30% compared with the SOC arm (72.2% vs 44.4%; P = .033), which was more prominent in the group with obesity (61.1% vs 27.7%; P = .033) than in the group without obesity (83.3% vs 61.1%; P = .352). The relative weight reduction was insignificant between the ICR and SOC arms (-5.3% vs -4.2%; P = .273); however, it was higher in the ICR arm compared with the SOC arm (-5.5% vs -2.9%; P = .039) in the group with obesity. Changes in fibrosis, muscle and fat mass, and liver enzyme levels were similar between the 2 groups (all P > .05). CONCLUSIONS: The ICR diet reduced LFC more effectively than SOC in patients with metabolic dysfunction-associated steatotic liver disease, particularly in patients with obesity. Additional studies are warranted in larger and more diverse cohorts. CLINICALTRIALS: gov, Number: NCT05309642.

Non-invasive prediction of post-sustained virological response hepatocellular carcinoma in hepatitis C virus: A systematic review and meta-analysis.

BACKGROUNDS/AIMS: Despite advances in antiviral therapy for hepatitis C virus (HCV) infection, hepatocellular carcinoma (HCC) still develops even after sustained viral response (SVR) in patients with advanced liver fibrosis or cirrhosis. This meta-analysis investigated the predictive performance of vibration-controlled transient elastography (VCTE) and fibrosis 4-index (FIB-4) for the development of HCC after SVR. METHODS: We searched PubMed, MEDLINE, EMBASE, and the Cochrane Library for studies examining the predictive performance of these tests in adult patients with HCV. Two authors independently screened the studies' methodological quality and extracted data. Pooled estimates of sensitivity, specificity, and area under the curve (AUC) were calculated for HCC development using random-effects bivariate logit normal and linear-mixed effect models. RESULTS: We included 27 studies (169,911 patients). Meta-analysis of HCC after SVR was possible in nine VCTE and 15 FIB-4 studies. Regarding the prediction of HCC development after SVR, the pooled AUCs of pre-treatment VCTE >9.2-13 kPa and FIB-4 >3.25 were 0.79 and 0.73, respectively. VCTE >8.4-11 kPa and FIB-4 >3.25 measured after SVR maintained good predictive performance, albeit slightly reduced (pooled AUCs: 0.77 and 0.70, respectively). The identified optimal cut-off value for HCC development after SVR was 12.6 kPa for pre-treatment VCTE. That of VCTE measured after the SVR was 11.2 kPa. CONCLUSION: VCTE and FIB-4 showed acceptable predictive performance for HCC development in patients with HCV who achieved SVR, underscoring their utility in clinical practice for guiding surveillance strategies. Future studies are needed to validate these findings prospectively and validate their clinical impact.

Treatment Response With Potassium-competitive Acid Blockers Based on Clinical Phenotypes of Gastroesophageal Reflux Disease: A Systematic Literature Review and Meta-analysis.

Background/Aims: Gastroesophageal reflux disease (GERD) is typically managed based on the clinical phenotype. We evaluated the efficacy and safety of potassium-competitive acid blockers (PCABs) in patients with various clinical GERD phenotypes. Methods: Core databases were searched for studies comparing PCABs and proton pump inhibitors (PPIs) in clinical GERD phenotypes of erosive reflux disease (ERD), non-erosive reflux disease (NERD), PPI-resistant GERD and night-time heartburn. Additional analysis was performed based on disease severity and drug dosage, and pooled efficacy was calculated. Results: In 9 randomized controlled trials (RCTs) evaluating the initial treatment of ERD, the risk ratio for healing with PCABs versus PPIs was 1.09 (95% CI, 1.04-1.13) at 2 weeks and 1.03 (95% CI, 1.00-1.07) at 8 weeks, respectively. PCABs exhibited a significant increase in both initial and sustained healing of ERD compared to PPIs in RCTs, driven particularly in severe ERD (Los Angeles grade C/D). In 3 NERD RCTs, PCAB was superior to placebo in proportion of days without heartburn. Observational studies on PPI-resistant symptomatic GERD reported symptom frequency improvement in 86.3% of patients, while 90.7% showed improvement in PPIresistant ERD across 5 observational studies. Two RCTs for night-time heartburn had different endpoints, limiting meta-analysis. Pronounced hypergastrinemia was observed in patients treated with PCABs. Conclusions: Compared to PPIs, PCABs have superior efficacy and faster therapeutic effect in the initial and maintenance therapy of ERD, particularly severe ERD. While PCABs may be an alternative treatment option in NERD and PPI-resistant GERD, findings were inconclusive in patients with night-time heartburn.

Association of modifiable metabolic risk factors and lifestyle with all-cause mortality in patients with hepatocellular carcinoma.

We aimed to investigate the potential impact of metabolic risk factors and lifestyles on mortality in hepatocellular carcinoma (HCC) patients. From the Korean Central Cancer Registry database (2008-2016), 8,505 HCC patients were included in the analysis. Patients with 2 or more metabolic risk factors (n = 2384, 28.0%) showed significantly worse overall survival (OS, 29 months, 95% confidence interval [CI] 27-33) than patients with 0 (n = 2269 [26.7%]; 41 months, 95% CI 37-47), or 1 (n = 3852 [45.3%]; 42 months; 95% CI 38-46) metabolic risk factor. (P < 0.001) In the multivariable Cox analysis, patients with ≥ 2 metabolic risk factors had significantly elevated risk of overall mortality (adjusted hazards ratio (HR) = 1.14 [95% CI 1.06-1.23], P < 0.001) and HCC-specific mortality (sub-distribution HR = 1.09 [95% CI 1.00-1.09], P = 0.046), compared to those without. Alcohol and smoking were also independent risk factors for worse overall and HCC-specific mortality (all P < 0.05). Metabolic comorbidities were associated with greater risk of mortality in a dose-dependent manner in HCC patients, regardless of tumor stage and liver function. Alcohol intake and smoking significantly increased mortality by themselves and even further with the presence of metabolic risk.

Validation of the Korean version of the Sleep Hygiene Practice Scale in a Non-Clinical Population.

OBJECTIVES: This study aimed to validate the Korean version of the sleep hygiene practice scale (SHPS-K) and determine its effectiveness in screening poor sleepers with insomnia. METHODS: Online survey was conducted using translated SHPS in Korean, the Korean versions of the Pittsburgh Sleep Quality Index (PSQI-K), Insomnia Severity Index (ISI-K), and Epworth Sleepiness Scale (KESS) in a non-clinical population. The internal consistency and test-retest reliability of the SHPS-K were assessed using Cronbach's alpha and intraclass correlation coefficients (ICC), respectively. Construct validity was evaluated using correlation analyses with other questionnaires and confirmatory factor analysis. We determined the cutoff values that could identify poor sleepers with insomnia symptoms (PSQI-K > 5 and ISI-K ≥ 15) using receiver operating characteristic analysis. RESULTS: A total of 484 participants (242 women, mean age of 43.8 years) were enrolled. The average SHPS-K score was 71.2, with no significant sex differences. Women had poorer sleep scheduling and timing behaviors, and men had poorer eating and drinking behaviors. Good internal consistency (Cronbach's alpha = 0.88) and test-retest reliability (ICC = 0.80) were observed. The SHPS-K was positively correlated with the PSQI-K (r = 0.55), ISI-K (r = 0.54), and KESS (r = 0.42). A cutoff value of 73 identified poor sleepers with insomnia (area under the curve = 0.828). CONCLUSIONS: The SHPS-K is a reliable instrument for evaluating sleep hygiene in non-clinical Korean populations.

The Combined Effects of Alcohol Consumption and Smoking on Cancer Risk by Exposure Level: A Systematic Review and Meta-Analysis.

BACKGROUND: Alcohol consumption is a major risk factor for cancer, and when combined with smoking, the risk increases. Nevertheless, few studies have comprehensively evaluated the combined effects of alcohol consumption and smoking on the risk of various cancer types. Therefore, to assess these effects, we conducted a systematic review and meta-analysis. METHODS: We performed a systematic search of five literature databases, focusing on cohort and case-control studies. Considering exposure levels, we quantified the combined effects of alcohol consumption and smoking on cancer risk and assessed multiplicative interaction effects. RESULTS: Of 4,452 studies identified, 24 (4 cohort studies and 20 case-control studies) were included in the meta-analysis. We detected interaction effect of light alcohol and moderate smoking on head and neck cancer risk (relative risk [RR], 4.26; 95% confidence interval [CI], 2.50-7.26; I² = 65%). A synergistic interaction was observed in heavy alcohol and heavy smoking group (RR, 35.24; 95% CI, 23.17-53.58; I² = 69%). In more detailed cancer types, the interaction effect of heavy alcohol and heavy smoking was noticeable on oral (RR, 36.42; 95% CI, 24.62-53.87; I² = 46%) and laryngeal (RR, 38.75; 95% CI, 19.25-78.01; I² = 69%) cancer risk. CONCLUSION: Our study provided a comprehensive summary of the combined effects of alcohol consumption and smoking on cancers. As their consumption increased, the synergy effect became more pronounced, and the synergy effect was evident especially for head and neck cancer. These findings provide additional evidence for the combined effect of alcohol and smoking in alcohol guidelines for cancer prevention.

Development and psychometric testing of a questionnaire for the Korea Youth risk behavior survey to assess physical activity behaviors.

BACKGROUND: Physical activity is essential for physical, mental, and cognitive health. Providing evidence to develop better public health policies to encourage increased physical activity is crucial. Therefore, we developed an in-depth survey as part of the Korea Youth Risk Behavior Survey to assess the current status and determinants of physical activity among Korean adolescents. METHODS: We developed an initial version of the questionnaire based on a review of validated questionnaires, recent trends and emerging issues related to adolescent physical activity, and the national public health agenda pertaining to health promotion. Content validity was confirmed by a panel of 10 experts. Face validity was confirmed through focus group interviews with 12 first-year middle school students. The test-retest reliability of the questionnaire was evaluated by administering it twice, approximately two weeks apart, to a sample of 360 middle and high school students. Additionally, the frequency or average number of responses was analyzed in a sample of 600 students who participated in the initial test-retest reliability evaluation of the questionnaire developed in this study. RESULTS: Through item pool generation and content and face validity test, the final 15 questionnaire items were developed across five themes: levels of physical activity, school sports club activities, transportation-related physical activity, physical activity-promoting environments, and factors mediating physical activity. The test-retest reliability ranged from fair to substantial. Results from the newly developed survey reveal that only a minority of adolescents engage in sufficient physical activity, with only 17.2% and 21.5% participating in vigorous and moderate-intensity activities, respectively, for at least five days per week. Among school-based activities, 44.3% of students do not participate in school sports clubs due to reasons including absence of clubs and disinterest in exercise. The major motivators for physical activity are personal enjoyment and health benefits, whereas preferences for other leisure activities and academic pressures are the predominant barriers. CONCLUSIONS: This study developed valid and reliable in-depth survey items to assess physical activity among Korean youths. It will hopefully enhance our understanding of adolescent physical activity, offering essential preliminary evidence to inform the development of public health strategies aimed at promoting adolescent health.

Handgrip strength thresholds associated with metabolic syndrome risk in children and adolescents: a systematic review and meta-analysis.

OBJECTIVES: Certain studies have reported that handgrip strength (HGS) is associated with metabolic health risks in children and adolescents, and some studies have suggested HGS thresholds for identifying poor metabolic health. Therefore, we aimed to determine the HGS thresholds associated with metabolic syndrome (MetS) in children and adolescents through a systematic review. METHODS: We searched 3 electronic databases from their inception until October 2023 to identify original papers that focused on children and adolescents and assessed their risks of MetS according to specific HGS values. Studies were selected for inclusion through a planned screening process based on specific criteria. The Quality Assessment Tool for Diagnostic Accuracy Studies version 2 (QUADAS-2) was used to evaluate quality, and a meta-analysis was performed using the diagmeta R package to suggest the optimal thresholds. RESULTS: From the search, 8 studies were selected for this systematic review. For detecting MetS risk, the optimal threshold for HGS (defined as relative HGS by adjusting for body mass) was found to be 0.422, with a sensitivity of 76.7% (95% confidence interval [CI], 64.0 to 85.8) and a specificity of 62.9% (95% CI, 56.9 to 68.5). The stratification analysis by sex resulted in optimal thresholds of 0.416 for boys and 0.376 for girls. Additionally, when the data were stratified by age, the thresholds were 0.356 for children and 0.416 for adolescents. CONCLUSIONS: Our results provide practical information for detecting high-risk groups and encouraging strength-related activities that may reduce the risk of MetS in children and adolescents.

Association between Thyroid Function and Insulin Resistance Indices in Korean Adolescents: Findings from the 2014-2015 Korea National Health and Nutrition Examination Survey.

AIM: This study investigated the sex-specific association between thyroid function and various insulin resistance (IR) indices, including noninsulin-based IR indices, in euthyroid adolescents. METHODS: A total of 465 adolescents (aged 12-18 years; 255 boys and 210 girls) based on data from the 2014-2015 Korea National Health and Nutrition Examination Survey were included. Serum thyrotropin (thyroid-stimulating hormone [TSH]) and free thyroxine (fT4) were used to assess thyroid function, whereas the homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin-sensitivity check index (QUICKI), glucose/insulin ratio (GIR), triglyceride-glucose (TyG) index, and triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio were used to assess IR. The relationship between thyroid function and IR was analyzed using multiple linear regressions stratified by sex, considering obesity status. RESULTS: The relationship between thyroid function and IR varied depending on sex and was more pronounced in the overweight/obesity subgroup for both boys and girls. In overweight and obese boys and girls, fT4 was significantly associated with HOMA-IR and QUICKI with conflicting association directions. TSH was also positively associated with the TyG index in both sexes. CONCLUSIONS: The findings suggest that the relationship between thyroid function and IR in adolescents might vary depending on sex, and the degree of association was significant in obese adolescents.

Validation of the Framingham Diabetes Risk Model Using Community-Based KoGES Data.

BACKGROUND: An 8-year prediction of the Framingham Diabetes Risk Model (FDRM) was proposed, but the predictor has a gap with current clinical standards. Therefore, we evaluated the validity of the original FDRM in Korean population data, developed a modified FDRM by redefining the predictors based on current knowledge, and evaluated the internal and external validity. METHODS: Using data from a community-based cohort in Korea (n = 5,409), we calculated the probability of diabetes through FDRM, and developed a modified FDRM based on modified definitions of hypertension (HTN) and diabetes. We also added clinical features related to diabetes to the predictive model. Model performance was evaluated and compared by area under the curve (AUC). RESULTS: During the 8-year follow-up, the cumulative incidence of diabetes was 8.5%. The modified FDRM consisted of age, obesity, HTN, hypo-high-density lipoprotein cholesterol, elevated triglyceride, fasting glucose, and hemoglobin A1c. The expanded clinical model added γ-glutamyl transpeptidase to the modified FDRM. The FDRM showed an estimated AUC of 0.71, and the model's performance improved to an AUC of 0.82 after applying the redefined predictor. Adding clinical features (AUC = 0.83) to the modified FDRM further improved in discrimination, but this was not maintained in the validation data set. External validation was evaluated on population-based cohort data and both modified models performed well, with AUC above 0.82. CONCLUSION: The performance of FDRM in the Korean population was found to be acceptable for predicting diabetes, but it was improved when corrected with redefined predictors. The validity of the modified model needs to be further evaluated.

Differences in coronary angiographic findings and outcomes between men and postmenopausal women with stable chest pain.

BACKGROUND: Despite the significant increase in cardiovascular events in women after menopause, studies comparing postmenopausal women and men are scarce. METHODS: We analyzed data from a nationwide, multicenter, prospective registry and enrolled 2412 patients with stable chest pain who underwent elective coronary angiography. Binary coronary artery disease (b-CAD) was defined as the ≥50% stenosis of epicardial coronary arteries, including the left main coronary artery. RESULTS: Compared with the men, postmenopausal women were older (66.6 ±â€…8.5 vs. 59.5 ±â€…11.4 years) and had higher high-density lipoprotein cholesterol levels (49.0 ±â€…12.8 vs. 43.6 ±â€…11.6 mg/dl, P  < 0.01). The prevalence of diabetes did not differ significantly ( P  = 0.40), and smoking was more common in men than in postmenopausal women ( P  ≤ 0.01). At enrollment, b-CAD and revascularization were more common in men than in postmenopausal women (50.3% vs. 41.0% and 14.4% vs. 9.7%, respectively; both P  < 0.01). However, multivariate analyses revealed that revascularization [odds ratio (OR): 0.72; 95% confidence interval (CI): 0.49-1.08] was not significantly related to sex and a similar result was found in age propensity-matched population (OR: 0.80; 95% CI: 0.52-1.24). During the follow-up period, the secondary composite cardiovascular outcomes were lower in postmenopausal women than in men (OR: 0.55; 95% CI: 0.31-0.98), also consistent with the result using the age propensity-mated population (OR: 0.33; 95% CI: 0.13-0.85). CONCLUSION: Postmenopausal women experienced coronary revascularization comparable to those in men at enrollment, despite the average age of postmenopausal women was 7 years older than that of men.Postmenopausal women exhibit better clinical outcomes than those of men if optimal treatment is provided.

PAGE-B incorporating moderate HBV DNA levels predicts risk of HCC among patients entering into HBeAg-positive chronic hepatitis B.

BACKGROUND & AIMS: Recent studies reported that moderate HBV DNA levels are significantly associated with hepatocellular carcinoma (HCC) risk in hepatitis B e antigen (HBeAg)-positive, non-cirrhotic patients with chronic hepatitis B (CHB). We aimed to develop and validate a new risk score to predict HCC development using baseline moderate HBV DNA levels in patients entering into HBeAg-positive CHB from chronic infection. METHODS: This multicenter cohort study recruited 3,585 HBeAg-positive, non-cirrhotic patients who started antiviral treatment with entecavir or tenofovir disoproxil fumarate at phase change into CHB from chronic infection in 23 tertiary university-affiliated hospitals of South Korea (2012-2020). A new HCC risk score (PAGED-B) was developed (training cohort, n = 2,367) based on multivariable Cox models. Internal validation using bootstrap sampling and external validation (validation cohort, n = 1,218) were performed. RESULTS: Sixty (1.7%) patients developed HCC (median follow-up, 5.4 years). In the training cohort, age, gender, platelets, diabetes and moderate HBV DNA levels (5.00-7.99 log10 IU/ml) were independently associated with HCC development; the PAGED-B score (based on these five predictors) showed a time-dependent AUROC of 0.81 for the prediction of HCC development at 5 years. In the validation cohort, the AUROC of PAGED-B was 0.85, significantly higher than for other risk scores (PAGE-B, mPAGE-B, CAMD, and REAL-B). When stratified by the PAGED-B score, the HCC risk was significantly higher in high-risk patients than in low-risk patients (sub-distribution hazard ratio = 8.43 in the training and 11.59 in the validation cohorts, all p <0.001). CONCLUSIONS: The newly established PAGED-B score may enable risk stratification for HCC at the time of transition into HBeAg-positive CHB. IMPACT AND IMPLICATIONS: In this study, we developed and validated a new risk score to predict hepatocellular carcinoma (HCC) development in patients entering into hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) from chronic infection. The newly established PAGED-B score, which included baseline moderate HBV DNA levels (5-8 log10 IU/ml), improved on the predictive performance of prior risk scores. Based on a patient's age, gender, diabetic status, platelet count, and moderate DNA levels (5-8 log10 IU/ml) at the phase change into CHB from chronic infection, the PAGED-B score represents a reliable and easily available risk score to predict HCC development during the first 5 years of antiviral treatment in HBeAg-positive patients entering into CHB. With a scoring range from 0 to 12 points, the PAGED-B score significantly differentiated the 5-year HCC risk: low <7 points and high ≥7 points.

Metabolically healthy obese individuals are still at high risk for diabetes: Application of the marginal structural model.

AIM: To assess the effect of obesity phenotype on the incidence of diabetes, considering phenotype as a time-varying exposure. METHODS: We used community-based cohort data from the Korean Genome and Epidemiology Study, with a 16-year follow-up period. Obesity phenotype was determined using body mass index and metabolic syndrome criteria. The influence of obesity phenotype on the occurrence of diabetes was evaluated using a Cox proportional hazard model and a marginal structural model (MSM). RESULTS: Obesity phenotypes were defined in 6265 individuals, with diabetes identified in 903 (14.4%) during the follow-up period. Individuals with metabolically healthy obesity (MHO) exhibited a higher risk of diabetes compared to those with metabolically healthy normal weight (MHNW), with a hazard ratio (HR) of 1.48 (95% confidence interval [CI] 1.15-1.90). This association remained significant after applying the MSM (HR 1.49, 95% CI 1.01-2.20). Moreover, various sensitivity analyses consistently demonstrated a higher risk of diabetes in individuals with MHO compared to those with MHNW. CONCLUSIONS: Even when obesity phenotype was treated as a time-varying exposure, individuals with MHO were still at higher risk for developing diabetes than those with MHNW. Consequently, such individuals should aim to avoid transitioning to a metabolically unfavourable state and strive to reduce their body weight to a normal range.

A network-based approach to explore comorbidity patterns among community-dwelling older adults living alone.

The detailed comorbidity patterns of community-dwelling older adults have not yet been explored. This study employed a network-based approach to investigate the comorbidity patterns of community-dwelling older adults living alone. The sample comprised a cross-sectional cohort of adults 65 or older living alone in a Korean city (n = 1041; mean age = 77.7 years, 77.6% women). A comorbidity network analysis that estimates networks aggregated from measures of significant co-occurrence between pairs of diseases was employed to investigate comorbid associations between 31 chronic conditions. A cluster detection algorithm was employed to identify specific clusters of comorbidities. The association strength was expressed as the observed-to-expected ratio (OER). As a result, fifteen diseases were interconnected within the network (OER > 1, p-value < .05). While hypertension had a high prevalence, osteoporosis was the most central disease, co-occurring with numerous other diseases. The strongest associations among comorbidities were found between thyroid disease and urinary incontinence, chronic otitis media and osteoporosis, gastric duodenal ulcer/gastritis and anemia, and depression and gastric duodenal ulcer/gastritis (OER > 1.85). Three distinct clusters were identified as follows: (a) cataracts, osteoporosis, chronic otitis media, osteoarthritis/rheumatism, low back pain/sciatica, urinary incontinence, post-accident sequelae, and thyroid diseases; (b) hyperlipidemia, diabetes mellitus, and hypertension; and (c) depression, skin disease, gastric duodenal ulcer/gastritis, and anemia. The results may prove valuable in guiding the early diagnosis, management, and treatment of comorbidities in older adults living alone.

Genetic predisposition, lifestyle inflammation score, food-based dietary inflammatory index, and the risk for incident diabetes: Findings from the KoGES data.

BACKGROUND AND AIMS: We investigated whether genetic predisposition, the Lifestyle Inflammation Score (LIS), or the Food-based Dietary Inflammatory Index (FDII) were associated with diabetes incidence and whether these factors interact. METHODS AND RESULTS: The study was conducted using population-based cohort data derived from the Korean Genome and Epidemiology Study, which included 6568 people aged 40-69 years. Based on 25 genetic variants related to diabetes, genetic risk scores (GRSs) were determined and LISs and FDIIs were calculated and stratified into quartiles. We investigated the effects of gene-lifestyle interactions on the incident diabetes. The multivariate Cox proportional hazard model was used to generate hazard ratios with 95 % CIs. During the 16-year follow-up period, diabetes incidence was 13.6 per 1000 person-years. A dose-response association with diabetes was observed for both GRS and LIS quartiles but not for FDII quartiles. The GRS and LIS were also independently associated with diabetes incidence in a multivariate model. Compared to the bottom quartile, the top LIS quartile and the top GRS quartile had a 2.4-fold (95 % CI, 2.0-2.8) and a 1.4-fold (95 % CI, 1.2-1.7) higher diabetes risk, respectively. However, the FDII exhibited null association. When each genetic variant was evaluated, the top versus bottom LIS quartiles exhibited heterogeneous diabetes risks for rs560887 within G6PC2, rs7072268 within HK1, and rs837763 within CDT1; however, these differences were not statistically significant in multiple comparison. CONCLUSION: Both GRS and LIS factors independently affect the incident diabetes, but their interaction effect showed insignificant association. Therefore, regardless of genetic susceptibility, more effort is needed to lower the risk for diabetes by improving lifestyle behaviors.

Effects of the multidomain intervention with nutritional supplements on cognition and gut microbiome in early symptomatic Alzheimer's disease: a randomized controlled trial.

Background: The SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN) is a part of the World-Wide Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (WW-FINGERS) network. This study aimed to demonstrate the effects of the SUPERBRAIN-based multidomain intervention with nutritional supplements in amyloid positive emission tomography (PET) proven early symptomatic Alzheimer's disease patients. Methods: Forty-six participants who were diagnosed with mild cognitive impairment or mild dementia and were positive in the amyloid PET study randomized into three groups: group A, the multidomain intervention with nutritional supplements; group B, nutritional supplements only; and a control group. The primary outcome was a change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score after an 8-week intervention. Secondary outcomes, including gut microbiome data, were also analyzed. Results: The RBANS total scale index score improved significantly in group A compared with group B (p < 0.032) and compared with the control group (p < 0.001). After intervention, beta diversity of the gut microbiome between group A and the control group increased, and patients in group A were more enriched with Bifidobacterium. Conclusion: SUPERBRAIN-based multidomain intervention with nutritional supplements improves cognition and gut microbiota in patients with early symptomatic Alzheimer's disease who were amyloid-positive by PET.

Metabolic complications of obesity in children and adolescents.

The global prevalence of childhood and adolescent obesity, exacerbated by the COVID-19 pandemic, is affecting not only school-aged children but also preschoolers. Early-onset obesity, along with a higher risk of metabolic complications, may contribute to a lower age of onset of cardiovascular disease (CVD). As metabolic diseases such as diabetes, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD) observed in adulthood are increasingly recognized in the pediatric population, there is an emphasis on moving disease susceptibility assessment from adulthood to childhood for early detection. Unlike adults, there is a lack of consensus in the definition of metabolic diseases in children. In response to this, various indicators such as pediatric simple metabolic syndrome score (PsiMS), continuous metabolic syndrome score (cMetS), single point insulin sensitivity estimator (SPISE), and fatty liver index (FLI) have been proposed in several studies. These indicators may help explain and early detect metabolic complications associated with pediatric obesity, although more validity studies are needed. Meanwhile, obesity assessment is shifting its perspective from visual obesity to metabolic health and body composition considerations to fill the gap in health impact assessment. Sarcopenic obesity, defined as muscle-to-fat ratio (MFR), has been proposed in pediatric populations and has also been found to be associated with metabolic health in children and adolescents. The National health screening program for children in Korea has expanded but still faces limitations in laboratory testing. These tests facilitate timely intervention by identifying high-risk groups for metabolic complications. Early detection and intervention through comprehensive health screening are critical to mitigate long-term complications of childhood obesity.