Non-invasive prediction of post-sustained virological response HCC in HCV: A systematic review and meta-analysis.

Background: 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 transient elastography (TE) 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 TE and 15 FIB-4 studies. Regarding the prediction of HCC development after SVR, the pooled AUCs of pre-treatment TE >9.2-13 kPa and FIB-4 >3.25 were 0.79 and 0.73, respectively. TE >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 TE. That of TE measured after the SVR was 11.2 kPa. Conclusion: TE 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.

Effects of intermittent calorie restriction in non-diabetic 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 (MASLD) patients. METHODS: This randomized controlled trial included patients with MRI-proton density fat fraction (PDFF) ≥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 (≥ or <25 kg/m2). The primary outcome was the proportion of patients who achieved a relative LFC reduction as measured by MRI-PDFF ≥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 to the SOC arm (72.2% vs. 44.4%; P=0.033), which was more prominent in the group with obesity (61.1% vs. 27.7%; P=0.033) than in the group without obesity (83.3% vs. 61.1%; P=0.352). The relative weight reduction was insignificant between the ICR and SOC arms (-5.3% vs. -4.2%; P=0.273); however, it was higher in the ICR arm compared to the SOC arm (-5.5% vs. -2.9%; P=0.039) in the group with obesity. Changes in fibrosis, muscle and fat mass, and liver enzyme levels were similar between the two groups (all P>0.05). CONCLUSIONS: The ICR diet reduced LFC more effectively than SOC in patients with MASLD, particularly in patients with obesity. Additional studies are warranted in larger and more diverse cohorts.

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.

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.

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.

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.

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 v2 (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. Conclusion: : 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.

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.

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.

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.

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.

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.

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.

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.

Cancer risk based on alcohol consumption levels: a comprehensive systematic review and meta-analysis.

OBJECTIVES: Alcohol consumption is a well-established risk factor for cancer. Despite extensive research into the relationship between alcohol consumption and cancer risk, the effect of light alcohol consumption on cancer risk remains a topic of debate. To contribute to this discourse, we conducted a comprehensive systematic review and meta-analysis. METHODS: Our systematic review aimed to investigate the associations between different levels of alcohol consumption and the risk of several cancer types. We focused on analyzing prospective associations using data from 139 cohort studies. Among them, 106 studies were included in the meta-analysis after a quantitative synthesis. RESULTS: Our analysis did not find a significant association between light alcohol consumption and all-cause cancer risk (relative risk, 1.02; 95% confidence interval, 0.99 to 1.04), but we observed a dose-response relationship. Light alcohol consumption was significantly associated with higher risks of esophageal, colorectal, and breast cancers. Light to moderate drinking was associated with elevated risks of esophageal, colorectal, laryngeal, and breast cancers. Heavy drinking was also found to contribute to the risk of stomach, liver, pancreas, and prostate cancers, thereby increasing the risk of almost all types of cancer. Additionally, females generally had lower cancer risks compared to males. CONCLUSIONS: Our findings highlight that cancer risks extend beyond heavy alcohol consumption to include light alcohol consumption as well. These findings suggest that there is no safe level of alcohol consumption associated with cancer risk. Our results underscore the importance of public health interventions addressing alcohol consumption to mitigate cancer risks.

Effect of 12-week intermittent calorie restriction compared to standard of care in patients with nonalcoholic fatty liver disease: a randomized controlled trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease. NAFLD can result in various complications. Owing to the lack of effective pharmacological therapies, lifestyle modifications are the cornerstone treatment for NAFLD. However, there has been no recommendation for a specific dietary therapy. Because no significant effects have been observed in previous studies. Intermittent calorie restriction (ICR) consists of alternating phases of extreme energy restriction and regular energy intake. Recent studies have demonstrated a significantly higher reduction in liver fat content in the ICR group than in the standard of care (SOC) or continuous calorie restriction groups in patients with NAFLD. However, critical weaknesses limit the broader application of ICR in clinical practice; those are a lack of appropriate assessment tools, different cutoffs of body mass index (BMI) used to define obesity, and different food portions. Thus, we report a protocol for a prospective, randomized controlled trial. The trial will evaluate the effect of 12-week ICR on improving liver fat content in NAFLD patients (Nonalcoholic Fatty Liver Disease-Intermittent Calorie Restriction [FLICR]). METHODS: We will include adult (19-75 years) NAFLD patients. NAFLD will be diagnosed by histologic assessment or magnetic resonance imaging-proton density fat fraction (MRI-PDFF) ≥ 8%. A total of 72 patients will be classified according to BMI (obese group: BMI ≥ 25 kg/m2 [n = 36] and non-obese group: BMI < 25 kg/m2 [n = 36]). Participants will be followed up for 24 weeks. Participants will be randomly assigned to one of the two groups: the SOC or ICR group. The primary objective will be the change in liver fat content measured using MRI-PDFF from baseline to 12 weeks. DISCUSSION: This FLICR study may provide clinical evidence on ICR in the treatment of NAFLD in both obese and non-obese patients. The use of ICR in patients with NAFLD will improve the clinical outcomes of patients facing a shortage of effective medical therapy. TRIAL REGISTRATION: This trial was registered at the United States National Library of Medicine (NLM) at the National Institutes of Health. CLINICALTRIALS: gov NCT05309642. Registered on April 4, 2022.

Association between use of vitamin and mineral supplement and non-alcoholic fatty liver disease in hypertensive adults.

Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic metabolic disorder in hypertensive adults. Impaired metabolism of micronutrients may increase NAFLD risk by exacerbating oxidative stress, insulin resistance, and inflammation among hypertensive adults. In this first cross-sectional analysis of 7,376 hypertensive adults with 2,015 NAFLD cases in the Korea National Health and Nutrition Examination Survey, vitamin and mineral supplements (VMS) use was identified via questionnaire. NAFLD was defined by a hepatic steatosis index > 36. Multivariable-adjusted odds ratios (MVOR) and 95% confidence intervals (CIs) were calculated using logistic regression models. In our study, 18.6% were current users of VMS; of these, 76.7% used multi-vitamin/mineral supplements. Current VMS users had significantly lower odds of NAFLD, compared with non-users (MVOR [95% CI]: 0.73 [0.58-0.92]). The inverse association became attenuated and non-significant among those consuming VMS at higher frequency (≥ 2 times/day), for longer duration (> 16 months), and taking ≥ 2 VMS products. The inverse association with current use of VMS was only evident in those aged < 56 years (MVOR [95% CI]: 0.54 [0.40-0.72]) and men (MVOR [95% CI]: 0.56 [0.40-0.80])(Pinteraction ≤ 0.04). Our results suggest that VMS use may lower NAFLD risk, particularly among younger or male hypertensive adults, if taken in moderation.