Human papillomavirus infection and cardiovascular mortality: a cohort study.

BACKGROUND AND AIMS: High-risk human papillomavirus (HR-HPV) infection-a well-established risk factor for cervical cancer-has associations with cardiovascular disease (CVD). However, its relationship with CVD mortality remains uncertain. This study examined the associations between HR-HPV infection and CVD mortality. METHODS: As part of a health examination, 163 250 CVD-free Korean women (mean age: 40.2 years) underwent HR-HPV screening and were tracked for up to 17 years (median: 8.6 years). National death records identified the CVD mortality cases. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD mortality were estimated using Cox proportional hazard regression analyses. RESULTS: During 1 380 953 person-years of follow-up, 134 CVD deaths occurred, with a mortality rate of 9.1 per 105 person-years for HR-HPV(-) women and 14.9 per 105 person-years for HR-HPV(+) women. After adjustment for traditional CVD risk factors and confounders, the HRs (95% CI) for atherosclerotic CVD (ASCVD), ischaemic heart disease (IHD), and stroke mortality in women with HR-HPV infection compared with those without infection were 3.91 (1.85-8.26), 3.74 (1.53-9.14), and 5.86 (0.86-40.11), respectively. The association between HR-HPV infection and ASCVD mortality was stronger in women with obesity than in those without (P for interaction = .006), with corresponding HRs (95% CI) of 4.81 (1.55-14.93) for obese women and 2.86 (1.04-7.88) for non-obese women. CONCLUSIONS: In this cohort study of young and middle-aged Korean women, at low risks for CVD mortality, those with HR-HPV infection had higher death rates from CVD, specifically ASCVD and IHD, with a more pronounced trend in obese individuals.

Screening mammography performance according to breast density: a comparison between radiologists versus standalone intelligence detection.

BACKGROUND: Artificial intelligence (AI) algorithms for the independent assessment of screening mammograms have not been well established in a large screening cohort of Asian women. We compared the performance of screening digital mammography considering breast density, between radiologists and AI standalone detection among Korean women. METHODS: We retrospectively included 89,855 Korean women who underwent their initial screening digital mammography from 2009 to 2020. Breast cancer within 12 months of the screening mammography was the reference standard, according to the National Cancer Registry. Lunit software was used to determine the probability of malignancy scores, with a cutoff of 10% for breast cancer detection. The AI's performance was compared with that of the final Breast Imaging Reporting and Data System category, as recorded by breast radiologists. Breast density was classified into four categories (A-D) based on the radiologist and AI-based assessments. The performance metrics (cancer detection rate [CDR], sensitivity, specificity, positive predictive value [PPV], recall rate, and area under the receiver operating characteristic curve [AUC]) were compared across breast density categories. RESULTS: Mean participant age was 43.5 ± 8.7 years; 143 breast cancer cases were identified within 12 months. The CDRs (1.1/1000 examination) and sensitivity values showed no significant differences between radiologist and AI-based results (69.9% [95% confidence interval [CI], 61.7-77.3] vs. 67.1% [95% CI, 58.8-74.8]). However, the AI algorithm showed better specificity (93.0% [95% CI, 92.9-93.2] vs. 77.6% [95% CI, 61.7-77.9]), PPV (1.5% [95% CI, 1.2-1.9] vs. 0.5% [95% CI, 0.4-0.6]), recall rate (7.1% [95% CI, 6.9-7.2] vs. 22.5% [95% CI, 22.2-22.7]), and AUC values (0.8 [95% CI, 0.76-0.84] vs. 0.74 [95% CI, 0.7-0.78]) (all P < 0.05). Radiologist and AI-based results showed the best performance in the non-dense category; the CDR and sensitivity were higher for radiologists in the heterogeneously dense category (P = 0.059). However, the specificity, PPV, and recall rate consistently favored AI-based results across all categories, including the extremely dense category. CONCLUSIONS: AI-based software showed slightly lower sensitivity, although the difference was not statistically significant. However, it outperformed radiologists in recall rate, specificity, PPV, and AUC, with disparities most prominent in extremely dense breast tissue.

Serum 25-Hydroxyvitamin D Levels and Risk of Colorectal Cancer: An Age-Stratified Analysis.

BACKGROUND & AIMS: The role of circulating 25-hydroxyvitamin D (25(OH)D) in the prevention of early-onset colorectal cancer (CRC) in young adults aged <50 years is uncertain. We evaluated the age-stratified associations (<50 vs ≥50 years) between circulating 25(OH)D levels and the risk of CRC in a large sample of Korean adults. METHODS: Our cohort study included 236,382 participants (mean age, 38.0 [standard deviation, 9.0] years) who underwent a comprehensive health examination, including measurement of serum 25(OH)D levels. Serum 25(OH)D levels were categorized as <10, 10 to 20, and ≥20 ng/mL. CRC, along with the histologic subtype, site, and invasiveness, was ascertained through linkage with the national cancer registry. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident CRC according to the serum 25(OH)D status, with adjustment for potential confounders. RESULTS: During the 1,393,741 person-years of follow-up (median, 6.5 years; interquartile range, 4.5-7.5 years), 341 participants developed CRC (incidence rate, 19.2 per 105 person-years). Among young individuals aged <50 years, serum 25(OH)D levels were inversely associated with the risk of incident CRC with HRs (95% CIs) of 0.61 (0.43-0.86) and 0.41 (0.27-0.63) for 25(OH)D 10 to 19 ng/mL and ≥20 ng/mL, respectively, with respect to the reference (<10 ng/mL) (P for trend <.001, time-dependent model). Significant associations were evident for adenocarcinoma, colon cancer, and invasive cancers. For those aged ≥50 years, associations were similar, although slightly attenuated compared with younger individuals. CONCLUSIONS: Serum 25(OH)D levels may have beneficial associations with the risk of developing CRC for both early-onset and late-onset disease.

The association of blood eosinophil counts and FEV1 decline: a cohort study.

BACKGROUND: Accelerated lung function decline is characteristic of COPD. However, the association between blood eosinophil counts and lung function decline, accounting for current smoking status, in young individuals without prevalent lung disease is not fully understood. METHODS: This is a cohort study of 629 784 Korean adults without COPD or a history of asthma at baseline who participated in health screening examinations including spirometry and differential white blood cell counts. We used a linear mixed-effects model to estimate the annual change in forced expiratory volume in 1 s (FEV1) (mL) by baseline blood eosinophil count, adjusting for covariates including smoking status. In addition, we performed a stratified analysis by baseline and time-varying smoking status. RESULTS: During a mean follow-up of 6.5 years (maximum 17.8 years), the annual change in FEV1 (95% CI) in participants with eosinophil counts <100, 100-199, 200-299, 300-499 and ≥500 cells·µL-1 in the fully adjusted model were -23.3 (-23.9--22.7) mL, -24.3 (-24.9--23.7) mL, -24.8 (-25.5--24.2) mL, -25.5 (-26.2--24.8) mL and -26.8 (-27.7--25.9) mL, respectively. When stratified by smoking status, participants with higher eosinophil count had a faster decline in FEV1 than those with lower eosinophil count in both never- and ever-smokers, which persisted when time-varying smoking status was used. CONCLUSIONS: Higher blood eosinophil counts were associated with a faster lung function decline among healthy individuals without lung disease, independent of smoking status. The findings suggest that higher blood eosinophil counts contribute to the risk of faster lung function decline, particularly among younger adults without a history of lung disease.

Association of Depression With the Progression of Multimorbidity in Older Adults: A Population-Based Cohort Study.

BACKGROUND: The relationship between depression and the risk of multimorbidity progression has rarely been studied in older adults. This study was aimed to determine whether depression is associated with progression in the severity and complexity of multimorbidity, considering the influence of depression's severity and subtype. METHODS: As a part of the Korean Longitudinal Study on Cognitive Aging and Dementia, this population-based cohort study followed a random sample of community-dwelling Koreans aged 60 and older for 8 years at 2-year intervals starting in 2010. Participants included those who completed mood and multimorbidity assessments and did not exhibit complex multimorbidity at the study's outset. Depression was assessed using the Geriatric Depression Scale, while multimorbidity was evaluated using the Cumulative Illness Rating Scale. The study quantified multimorbidity complexity by counting affected body systems and measured multimorbidity severity by averaging scores across 14 body systems. FINDINGS: The 2,486 participants (age = 69.1 ± 6.5 years, 57.6% women) were followed for 5.9 ± 2.4 years. Linear mixed models revealed that participants with depression had a faster increase in multimorbidity complexity score (ß = .065, SE = 0.019, p = 0.001) than those without depression, but a comparable increase in multimorbidity severity score (ß = .001, SE = .009, p = 0.870) to those without depression. Cox proportional hazard models revealed that depression was associated with the risk of developing highly complex multimorbidity affecting five or more body systems, particularly in severe or anhedonic depression. INTERPRETATION: Depression was associated with the worsening of multimorbidity in Korean older adults, particularly when severe or anhedonic. Early screening and management of depression may help to reduce the burden of multimorbidity in older adults.

Baseline and change in serum uric acid level over time and resolution of nonalcoholic fatty liver disease in young adults: The Kangbuk Samsung Health Study.

AIMS: To determine the association between: (i) baseline serum uric acid (SUA) level and (ii) SUA changes over time, and nonalcoholic fatty liver disease (NAFLD) resolution. MATERIALS AND METHODS: A retrospective cohort study, comprising 38 483 subjects aged <40 years with pre-existing NAFLD, was undertaken. The effects of SUA changes over time were studied in 25 266 subjects. Participants underwent a health examination between 2011 and 2019, and at least one follow-up liver ultrasonography scan up to December 2020. Exposures included baseline SUA level and SUA changes between baseline and subsequent visits, categorized into quintiles. The reference group was the third quintile (Q3) containing zero change. The primary endpoint was resolution of NAFLD. RESULTS: During a median follow-up of 4 years, low baseline SUA level and decreases in SUA levels over time were independently associated with NAFLD resolution (p for trend <0.001). Using SUA as a continuous variable, the likelihood of NAFLD resolution was increased by 10% and 13% in men and women, respectively, per 1-mg/dL decrease in SUA. In a time-dependent model with changes in SUA treated as a time-varying covariate, adjusted hazard ratios (95% confidence intervals) for NAFLD resolution comparing Q1 (highest decrease) and Q2 (slight decrease) to Q3 (reference) were 1.63 (1.49-1.78) and 1.23 (1.11-1.35) in men and 1.78 (1.49-2.12) and 1.18 (0.95-1.46) in women, respectively. CONCLUSIONS: Low baseline SUA levels and a decrease in SUA levels over time were both associated with NAFLD resolution in young adults.

Gate-bias stability of triple-gated feedback field-effect transistors with silicon nanosheet channels.

In this study, we investigate the gate-bias stability of triple-gated feedback field-effect transistors (FBFETs) with Si nanosheet channels. The subthreshold swing (SS) of FBFETs increases from 0.3 mV dec-1to 60 and 80 mV dec-1inp- andn-channel modes, respectively, when a positive bias stress (PBS) is applied for 1000 s. In contrast, the SS value does not change even after a negative bias stress (NBS) is applied for 1000 s. The difference in the switching characteristics under PBS and NBS is attributed to the ability of the interface traps to readily gain electrons from the inversion layer. The switching characteristics deteriorated by PBS are completely recovered after annealing at 300 °C for 10 min, and the characteristics remain stable even after PBS is applied again for 1000 s.

Risk prediction model for gastric cancer within 5 years in healthy Korean adults.

BACKGROUND: Although endoscopy is commonly used for gastric cancer screening in South Korea, predictive models that integrate endoscopy results are scarce. We aimed to develop a 5-year gastric cancer risk prediction model using endoscopy results as a predictor. METHODS: We developed a predictive model using the cohort data of the Kangbuk Samsung Health Study from 2011 to 2019. Among the 260,407 participants aged ≥20 years who did not have any previous history of cancer, 435 cases of gastric cancer were observed. A Cox proportional hazard regression model was used to evaluate the predictors and calculate the 5-year risk of gastric cancer. Harrell's C-statistics and Nam-D'Agostino χ2 test were used to measure the quality of discrimination and calibration ability, respectively. RESULTS: We included age, sex, smoking status, alcohol consumption, family history of cancer, and previous results for endoscopy in the risk prediction model. This model showed sufficient discrimination ability [development cohort: C-Statistics: 0.800, 95% confidence interval (CI) 0.770-0.829; validation cohort: C-Statistics: 0.799, 95% CI 0.743-0.856]. It also performed well with effective calibration (development cohort: χ2 = 13.65, P = 0.135; validation cohort: χ2 = 15.57, P = 0.056). CONCLUSION: Our prediction model, including young adults, showed good discrimination and calibration. Furthermore, this model considered a fixed time interval of 5 years to predict the risk of developing gastric cancer, considering endoscopic results. Thus, it could be clinically useful, especially for adults with endoscopic results.

Potential role of Fibrosis-4 score in hepatocellular carcinoma screening: The Kangbuk Samsung Health Study.

AIM: Hepatocellular carcinoma (HCC) is a major cause of cancer-related death, with low survival rates worldwide. Fatty liver disease (FLD) significantly contributes to HCC. We studied the screening performance of different methods for identifying HCC in patients with FLD or with metabolic risk factors for FLD. METHODS: Korean adults (n = 340 825) without a prior HCC diagnosis were categorized into four groups: normal (G1), ≥2 metabolic risk factors (G2), FLD (G3), and viral liver disease or liver cirrhosis (G4). The National Cancer Registry data were used to identify HCC cases within 12 months. We assessed the area under the receiver operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of individual or combined screening methods. RESULTS: In 93 HCC cases, 71 were identified in G4, whereas 20 cases (21.5%) in G2 and G3 combined where ultrasound and Fibrosis-4 performed similarly to alpha-fetoprotein and ultrasound. In G2, Fibrosis-4 and ultrasound had the highest area under the receiver operating characteristic curve (0.93 [0.87-0.99]), whereas in G3, the combined screening methods had the highest area under the receiver operating characteristic curve (0.98 [0.95-1.00]). The positive predictive value was lower in G2 and G3 than in G4, but was >5% when restricted to a high Fibrosis-4 score. CONCLUSIONS: More than 21% of HCC cases were observed in patients with diagnosed FLD or at risk of FLD with metabolic risk factors. Nevertheless, screening for HCC in individuals without cirrhosis or viral hepatitis yielded very low results, despite the potential value of the Fibrosis-4 score in identifying individuals at high risk of HCC.

Impact of metabolic unhealthiness and its changes on the risk of erosive esophagitis: a cohort study.

BACKGROUND AND AIM: We aimed to compare the risk of erosive esophagitis (EE) among individuals with different phenotypes based on metabolic health status and obesity and investigate the role of changes in metabolic health in EE risk. METHODS: A cohort of 258 892 asymptomatic adults without EE at baseline who underwent ollow-up esophagogastroduodenoscopy (EGD) were categorized into the following four groups according to metabolic health and obesity status: (i) metabolically healthy (MH) non-obese; (ii) metabolically unhealthy (MU) non-obese; (iii) MH obese; and (iv) MU obese. EE was defined as the presence of grade A or higher mucosal breaks on EGD. RESULTS: During a median follow-up of 4.5 years, the incidence rates of EE were 0.6/103 person-years (PY), 1.7/103 PY, 1.7/103 PY, and 3.1/103 PY in the MH non-obese, MU non-obese, MH obese, and MU obese groups, respectively. The multivariable-adjusted hazard ratio (HR) (95% confidence intervals [CI]) for developing EE comparing the MH obese, MU non-obese, and MU obese groups with the MH non-obese group were 1.49 (1.29-1.71), 1.56 (1.25-1.94), and 2.18 (1.90-2.49), respectively. The multivariable-adjusted HR (95% CI) comparing the progression of MH to MU, regression of MU to MH, and persistent MU with the persistent MH group were 1.39 (1.10-1.76), 1.39 (1.09-1.77), and 1.86 (1.56-2.21), respectively. The increased risk of EE among the persistent MU group was consistently observed in individuals without obesity or abdominal obesity. CONCLUSION: Metabolic unhealthiness and obesity were independent risk factors for the development of EE, suggesting that maintaining both normal weight and metabolic health may help reduce the risk of EE.

Isolated Hepatitis B Core Antibody Positivity and Long-Term Liver-Related Mortality in Korea: A Cohort Study.

INTRODUCTION: Whether isolated hepatitis B core antibody (anti-HBc) positivity is a risk factor for long-term liver-related outcomes in hepatitis B virus (HBV)-endemic areas remains unclear. We aimed to investigate liver-related and liver cancer mortality of isolated anti-HBc positivity in Korean adults. METHODS: A cohort study comprised 609,299 Korean adults who underwent hepatitis B serologic markers, as a part of health examination. Liver-related and liver cancer mortality were determined using the National Death Records. RESULTS: During a median follow-up of 9.0 years (interquartile range, 5.5-13.7 years), 554 liver-related deaths were identified (liver-related mortality, 9.6 cases per 10 5 person-years). The prevalence of isolated anti-HBc positivity was 3.8% (n = 23,399) and was age-dependent. After adjustment for age, sex, and other confounders, hazard ratios (95% confidence interval) for liver-related mortality in isolated anti-HBc-positive and hepatitis B surface antigen-positive subjects compared with HBV-unexposed subjects were 1.69 (1.22-2.33) and 27.02 (21.45-34.04), respectively. These associations were pronounced in the analyses using liver cancer mortality as an outcome. Among isolated anti-HBc-positive patients, the risks of liver-related and liver cancer mortality were significantly higher in those with high fibrosis-4 scores compared with patients unexposed to HBV with the multivariable-adjusted hazard ratios (95% confidence interval) of 15.59 (9.21-26.37) and 72.66 (36.96-142.86), respectively. DISCUSSION: In this cohort of Korean adults, isolated anti-HBc positivity was associated with an increased risk of liver-related and liver cancer mortality, especially when accompanied by a high fibrosis score. Isolated anti-HBc positivity may be an independent risk factor for liver-related outcomes, especially in high-endemic areas.

History of Gestational Diabetes and Incident Nonalcoholic Fatty Liver Disease: The Kangbuk Samsung Health Study.

INTRODUCTION: We examined the relationship between a previous history of gestational diabetes mellitus (pGDM) and risk of incident nonalcoholic fatty liver disease (NAFLD) and investigated the effect of insulin resistance or development of diabetes as mediators of any association. METHODS: We performed a retrospective cohort study of 64,397 Korean parous women without NAFLD. The presence of and the severity of NAFLD at baseline and follow-up were assessed using liver ultrasonography. Cox proportional hazards models were used to determine adjusted hazard ratios for incident NAFLD according to a self-reported GDM history, adjusting for confounders as time-dependent variables. Mediation analyses were performed to examine whether diabetes or insulin resistance may mediate the association between pGDM and incident NAFLD. RESULTS: During a median follow-up of 3.7 years, 6,032 women developed incident NAFLD (of whom 343 had moderate-to-severe NAFLD). Multivariable adjusted hazard ratios (95% confidence intervals) comparing women with time-dependent pGDM with the reference group (no pGDM) were 1.46 (1.33-1.59) and 1.75 (1.25-2.44) for incident overall NAFLD and moderate-to-severe NAFLD, respectively. These associations remained significant in analyses restricted to women with normal fasting glucose <100 mg/dL or that excluded women with prevalent diabetes at baseline or incident diabetes during follow-up. Diabetes and insulin resistance (Homeostatic Model Assessment for Insulin Resistance) each mediated <10% of the association between pGDM and overall NAFLD development. DISCUSSION: A previous history of GDM is an independent risk factor for NAFLD development. Insulin resistance, measured by the Homeostatic Model Assessment for Insulin Resistance, and development of diabetes each explained only <10% of the association between GDM and incident NAFLD.

Diagnostic performance of screening mammography according to menstrual cycle among Asian women.

PURPOSE: To investigate the performance metrics of screening mammography according to menstrual cycle week in premenopausal Asian women. METHODS: This retrospective study included 69,556 premenopausal Asian women who underwent their first screening mammography between 2011 and 2019. The presence or absence of a breast cancer diagnosis within 12 months after the index screening mammography served as the reference standard, determined by linking the study data to the national cancer registry data. Menstrual cycles were calculated, and participants were assigned to groups according to weeks 1-4. The performance metrics included cancer detection rate (CDR), sensitivity, specificity, and positive predictive value (PPV), with comparisons across menstrual cycles. RESULTS: Among menstrual cycles, the lowest CDR at 4.7 per 1000 women (95% confidence interval [CI], 3.8-5.8 per 1000 women) was observed in week 4 (all P < 0.05). The highest sensitivity of 72.7% (95% CI, 61.4-82.3) was observed in week 1, although the results failed to reach statistical significance. The highest specificity of 80.4% (95% CI, 79.5-81.3%) was observed in week 1 (P = 0.01). The lowest PPV of 2.2% (95% CI, 1.8-2.7) was observed in week 4 (all P < 0.05). CONCLUSION: Screening mammography tended to show a higher performance during week 1 and a lower performance during week 4 of the menstrual cycle among Asian women. These results emphasize the importance of timing recommendations that consider menstrual cycles to optimize the effectiveness of screening mammography for breast cancer detection.

What is the impact of one's chronic illness on his or her spouse's future chronic illness: a community-based prospective cohort study.

BACKGROUND: Integrating a joint approach to chronic disease management within the context of a couple has immense potential as a valuable strategy for both prevention and treatment. Although spousal concordance has been reported in specific chronic illnesses, the impact they cumulatively exert on a spouse in a longitudinal setting has not been investigated. We aimed to determine whether one's cumulative illness burden has a longitudinal impact on that of their spouse. METHODS: Data was acquired from a community-based prospective cohort that included Koreans aged 60 years and over, randomly sampled from 13 districts nationwide. Data from the baseline assessment (conducted from November 2010 to October 2012) up to the 8-year follow-up assessment was analyzed from October 2021 to November 2022. At the last assessment, partners of the index participants were invited, and we included 814 couples in the analysis after excluding 51 with incomplete variables. Chronic illness burden of the participants was measured by the Cumulative Illness Rating Scale (CIRS). Multivariable linear regression and causal mediation analysis were used to examine the longitudinal effects of index chronic illness burden at baseline and its change during follow-up on future index and spouse CIRS scores. RESULTS: Index participants were divided based on baseline CIRS scores (CIRS < 6 points, n = 555, mean [SD] age 66.3 [4.79] years, 43% women; CIRS ≥ 6 points, n = 259, mean [SD] age 67.7 [4.76] years, 36% women). The baseline index CIRS scores and change in index CIRS scores during follow-up were associated with the spouse CIRS scores (ß = 0.154 [SE: 0.039], p < 0.001 for baseline index CIRS; ß = 0.126 [SE: 0.041], p = 0.002 for change in index CIRS) at the 8-year follow-up assessment. Subgroup analysis found similar results only in the high CIRS group. The baseline index CIRS scores and change in index CIRS scores during follow-up had both direct and indirect effects on the spouse CIRS scores at the 8-year follow-up assessment. CONCLUSIONS: The severity and course of one's chronic illnesses had a significant effect on their spouse's future chronic illness particularly when it was severe. Management strategies for chronic diseases that are centered on couples may be more effective.

Risk of CKD Following Detection of Microscopic Hematuria: A Retrospective Cohort Study.

RATIONALE & OBJECTIVE: Microscopic hematuria is an uncertain risk factor for chronic kidney disease (CKD). We investigated the association between persistent or single episodes of microscopic hematuria and the development of incident CKD, overall and separately among men and women. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: A total of 232,220 Korean adults without CKD at baseline who underwent repeated regular health examinations at Kangbuk Samsung Health Study formed the study cohort. EXPOSURE: Microscopic hematuria was defined by≥5 red blood cells per high-power field. Participants were categorized into 1 of 4 groups according to the presence of hematuria at 2 consecutive examinations: (1) no hematuria at both examinations (reference group); (2) hematuria followed by no hematuria (regressed hematuria group); (3) no hematuria followed by hematuria (developed hematuria group); and (4) hematuria at both examinations (persistent hematuria group). OUTCOME: CKD was defined as an estimated glomerular filtration rate<60mL/min/1.73m2 or proteinuria (1+or more on dipstick examination). ANALYTICAL APPROACH: Semiparametric proportional hazards models were used to estimate hazard ratios. RESULTS: During a 4.8-year median follow-up period, 2,392 participants developed CKD. Multivariable-adjusted hazard ratios for incident CKD, comparing the regressed, developed, and persistent hematuria groups to the no-hematuria group were 1.85 (95% CI, 1.35-2.53), 3.18 (95% CI, 2.54-3.98), and 5.23 (95% CI, 4.15-6.59), respectively. The association between persistent hematuria and incident CKD was stronger in men than women (P for interaction<0.001), although a statistically significant association was observed in both sexes. LIMITATIONS: Lack of albuminuria and inability to consider specific glomerular diseases. CONCLUSIONS: Men and women with microscopic hematuria, especially persistent hematuria, may be at increased risk of CKD.

NAFLD improves risk prediction of type 2 diabetes: with effect modification by sex and menopausal status.

BACKGROUND AND AIMS: The effects of sex and menopausal status on the association between NAFLD and incident type 2 diabetes (T2D) remain unclear. We investigated the effect modification by sex and menopause in the association between NAFLD and T2D; also, the added predictive ability of NAFLD for the risk of T2D was assessed. APPROACH AND RESULTS: This cohort study comprised 245,054 adults without diabetes (109,810 premenopausal women; 4958 postmenopausal women; 130,286 men). Cox proportional hazard models were used to estimate hazard ratios (HRs; 95% confidence intervals [CIs]) for incident T2D according to NAFLD status. The incremental predictive role of NAFLD for incident T2D was assessed using the area under the receiver operating characteristic curve, net reclassification improvement, and integrated discrimination improvement. A total of 8381 participants developed T2D (crude incidence rate/103 person-years: 2.9 premenopausal women; 12.2 postmenopausal women; 9.3 men) during median follow-up of 5.3 years. NAFLD was positively associated with incident T2D in all groups. After adjustment for potential confounders, the multivariable-adjusted HRs (95% CIs) for incident T2D comparing NAFLD to no NAFLD were 4.63 (4.17-5.14), 2.65 (2.02-3.48), and 2.16 (2.04-2.29) in premenopausal women, postmenopausal women, and men, respectively. The risks of T2D increased with NAFLD severity as assessed by serum fibrosis markers, and the highest relative excess risks were observed in premenopausal women. The addition of NAFLD to conventional risk factors improved risk prediction for incident T2D in both sexes, with a greater improvement in women than men. CONCLUSIONS: NAFLD, including more severe NAFLD, is a stronger risk factor for incident T2D in premenopausal women than in postmenopausal women or men; protection against T2D is lost in premenopausal women with NAFLD.

The impact of the COVID-19 pandemic on depression in community-dwelling older adults: a prospective cohort study.

BACKGROUND: There are growing concerns about the impact of the COVID-19 pandemic on the mental health of older adults. We examined the effect of the pandemic on the risk of depression in older adults. METHODS: We analyzed data from the prospective cohort study of Korean older adults, which has been followed every 2 years. Among the 2308 participants who completed both the third and the fourth follow-up assessments, 58.4% completed their fourth follow-up before the outbreak of COVID-19 and the rest completed it during the pandemic. We conducted face-to-face diagnostic interviews using Mini International Neuropsychiatric Interview and used Geriatric Depression Scale. We performed generalized estimating equations and logistic regression analyses. RESULTS: The COVID-19 pandemic was associated with increased depressive symptoms in older adults [b (standard error) = 0.42 (0.20), p = 0.040] and a doubling of the risk for incident depressive disorder even in euthymic older adults without a history of depression (odds ratio = 2.44, 95% confidence interval 1.18-5.02, p = 0.016). Less social activities, which was associated with the risk of depressive disorder before the pandemic, was not associated with the risk of depressive disorder during the pandemic. However, less family gatherings, which was not associated with the risk of depressive disorder before the pandemic, was associated with the doubled risk of depressive disorder during the pandemic. CONCLUSIONS: The COVID-19 pandemic significantly influences the risk of late-life depression in the community. Older adults with a lack of family gatherings may be particularly vulnerable.

Nonalcoholic fatty liver disease without overlapping metabolic-associated fatty liver disease and the risk of incident type 2 diabetes.

BACKGROUND AND AIMS: Re-classifying NAFLD as metabolic-associated fatty liver (MAFLD) has been proposed. While some people fulfil criteria for NAFLD, they do not have MAFLD; and whether NAFLD-only subjects have increased the risk of type 2 diabetes remains unknown. We compared risk of incident T2D in individuals with: (a) NAFLD-only; and (b) MAFLD, to individuals without fatty liver, considering effect modification by sex. METHODS: 246 424 Koreans without diabetes or a secondary cause of ultrasound-diagnosed hepatic steatosis were studied. Subjects were stratified into: (a) NAFLD-only status and (b) NAFLD that overlapped with MAFLD (MAFLD). Cox proportional hazards models with incident T2D as the outcome were used to estimate hazard ratios (HRs) for: (a) and (b). Models were adjusted for time-dependent covariates, and effect modification by sex was analysed in subgroups. RESULTS: A total of 5439 participants had NAFLD-only status and 56 839 met MAFLD criteria. During a median follow-up of 5.5 years, 8402 incident cases of T2D occurred. Multivariable-adjusted HRs (95% CI) for incident T2D comparing NAFLD-only and MAFLD to the reference (neither condition) were 2.39 (1.63-3.51) and 5.75 (5.17-6.36) (women), and 1.53 (1.25-1.88) and 2.60 (2.44-2.76) (men), respectively. The increased risk of T2D in the NAFLD-only group was higher in women than in men (p for interaction by sex <0.001) and consistently observed across all subgroups. Risk of T2D was increased in lean participants regardless of metabolic dysregulation (including prediabetes). CONCLUSIONS: NAFLD-only participants without metabolic dysregulation and the criteria for MAFLD are at increased risk of developing T2D. This association was consistently stronger in women than in men.

Metabolic-associated fatty liver disease is associated with colorectal adenomas in young and older Korean adults.

BACKGROUND AND AIMS: Given that the majority of colorectal cancers (CRCs) develop from high-risk adenomas, identifying risk factors for high-risk adenomas is important. The relationship between metabolic dysfunction-associated fatty liver disease (MAFLD) and the risk of colorectal adenoma in young adults remains unclear. We aimed to evaluate this relationship in adults <50 (younger) and ≥50 (older) years of age. METHODS: This cross-sectional study included 184 792 Korean adults (80% <50 years of age) who all underwent liver ultrasound and colonoscopy. Participants were grouped into those with and without MAFLD and classified by adenoma presence into no adenoma, low-risk adenoma, or high-risk adenoma (defined as ≥3 adenomas, any ≥10 mm, or adenoma with high-grade dysplasia/villous features). RESULTS: The prevalence of low- and high-risk adenomas among young and older adults was 9.6% and 0.8% and 22.3% and 4.8%, respectively. MAFLD was associated with an increased prevalence of low- and high-risk adenomas in young and older adults. Young adults with MAFLD had a 1.30 (95% CIs 1.26-1.35) and 1.40 (1.23-1.59) times higher prevalence of low- and high-risk adenomas, respectively, compared to those without MAFLD. These associations were consistent even in lean adults (BMI < 23 kg/m2 ) and those without a family history of CRC. CONCLUSIONS: MAFLD is associated with an increased prevalence of low- and high-risk adenomas in Korean adults, regardless of age or obesity status. Whether reducing metabolic risk factors, such as MAFLD, reduces the risk of precancerous lesions and ultimately reduces the risk of early-onset CRC requires further investigation.

Coronary artery calcium and risk of chronic kidney disease in young and middle-aged adults.

BACKGROUND: The role of the coronary artery calcium score (CACS) in incident chronic kidney disease (CKD) in asymptomatic young populations remains unclear. The aim of this study was to evaluate the association between CACSs and CKD development in adults. METHODS: A cohort study of 113 171 Korean adults (mean age 40.6 years) without CKD and proteinuria at baseline who underwent a cardiac tomography estimation of CACSs during health screening examinations was performed (median follow-up 4.2 years). The outcome was CKD, defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2 and/or the presence of proteinuria. Hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD were estimated using Cox proportional hazards regression analyses. RESULTS: A higher CACS was moderately associated with an increased risk of CKD in a dose-dependent manner. The multivariable-adjusted HRs for CKD comparing CACSs 1-100, 101-300 and >300 with a CACS of 0 were 1.15 (95% CI 1.05-1.25), 1.37 (95% CI 1.13-1.66) and 1.71 (95% CI 1.32-2.22), respectively (P for trend <.001). When CKD was defined using low eGFR and proteinuria separately, corresponding HRs for low eGFR were 1.31 (95% CI 1.05-1.62), 1.41 (95% CI 0.95-2.11) and 1.86 (95% CI 1.16-3.00), respectively (P for trend = .001), while the HRs for proteinuria were 1.11 (95% CI 1.02-1.21), 1.32 (95% CI 1.07-1.64) and 1.57 (95% CI 1.16-2.12), respectively. CONCLUSIONS: A higher CACS was progressively associated with an increased risk of CKD, even at low CACSs. Individuals with a CACS >0 appear to have an increased risk of CKD and may benefit from preventive measures to reduce CKD risk.