Epidemiology and treatment outcome of ANCA-associated vasculitis in South Korea: a nationwide, population-based cohort study.

OBJECTIVES: To investigate the epidemiological features of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) in South Korea. METHODS: We identified the index cases of GPA and MPA using the 2010-2018 Korean National Health Insurance Service database and the Rare Intractable Disease registry for the entire Korean population. Each disease's incidence and prevalence rates and trends over time were analysed. To assess the impact of disease on morbidity and mortality, a comparator group comprising the general population was established using nearest-neighbour matching by age, sex, income, and comorbidity index, at a 5:1 ratio. Morbidity outcomes included the initiation of renal replacement therapy and admission to the intensive care unit. RESULTS: We identified 546 and 795 patients with GPA and MPA, respectively. The incidence rates of both diseases increased with age, with peak incidence rates observed among patients aged ≥70 years. The incidence of MPA increased continuously over time, whereas that of GPA showed no significant changes. During the observation period, 132 (28.7%) and 277 (41.1%) patients in the GPA and MPA groups, respectively, died, which were significantly higher than that in the general population (standardised mortality ratio: 3.53 and 5.58, respectively) and comparator group (hazard ratio: 4.02 and 5.64, respectively). Higher mortality and morbidity rates were observed among patients with MPA than among those with GPA. CONCLUSIONS: In South Korea, the incidence of MPA has increased over time. Although both GPA and MPA had high rates of mortality and morbidity, MPA has a poorer prognosis than GPA.

Association between body composition and subsequent cardiovascular diseases among 5-year breast cancer survivors.

BACKGROUND AND AIMS: Cardiovascular disease (CVD) remain one of the leading causes of mortality in breast cancer survivors. This study aimed to investigate the association between body composition and subsequent CVD in breast cancer survivors. METHODS AND RESULTS: A retrospective cohort study of more than 70 thousand 5-year breast cancer survivors aged 40 years or older was conducted using data from the National Health Insurance Service of South Korea. Based on the percentage of predicted lean body mass (pLBMP), appendicular skeletal muscle mass (pASMP), and body fat mass (pBFMP), which were calculated using prediction equations with anthropometric data and health habits, groups were equally divided into quartiles. The risk of CVD was evaluated using multivariate Cox proportional hazards regression. Compared to those with the lowest pLBMP and pASMP, those with the highest pLBMP and pASMP had a 38% and 42% lower risk of CVD, respectively. In contrast, those with the highest pBFMP had a 57% higher risk of CVD compared to those with the lowest pBFMP. Each 1 % increase in pLBMP and pASMP was associated with a decreased risk of CVD [pLBMP, adjusted hazard ratio (aHR): 0.96, 95% CI 0.94-0.98, p < 0.05; pASMP, aHR: 0.91, 95% CI 0.87-0.95, p < 0.05] while each 1 % increase in pBFMP was associated with the increased risk of CVD (aHR: 1.05, 95% CI 1.03-1.07, p < 0.01). CONCLUSION: In this cohort study, a high pLBMP, a high pASMP, and a low pBFMP were associated with a lower risk of CVD.

Association of parental depression with adolescent children's psychological well-being and health behaviors.

BACKGROUND: Parental depression is a significant problem that negatively affects parents' welfare and influences family dynamics, children's academic and health behaviors, and mental health. However, there is limited evidence regarding the impact of the parental depression into the children's' psychological and physical wellbeing on Asian cultures. This study examined the psychological burdens and health behaviors of adolescent children with parents with depression in the Republic of Korea. METHODS: We conducted a cross-sectional study using data from the Korean National Health and Nutrition Examination Survey (KNHANES) spanning 2013 to 2021 to compare health behaviors and mental health outcomes between 203 adolescent children with parents diagnosed with depression and 3,856 control adolescents aged 12-19 years. RESULTS: Following multivariate adjustments, the risk of depressive mood for more than two weeks was significantly increased in boys with parental depression (adjusted Odds Ratio [aOR] = 2.05, 95% Confidence Interval [CI] = 1.91-3.52) and adolescents with parents with moderate-to-severe depression (aOR = 2.60, 95% CI = 1.17-5.77). Adolescents with parental depression reported significantly worse subjective health status (aOR = 1.88, 95% CI = 1.05-3.36) and higher stress levels (aOR = 1.91, 95% CI = 1.33-2.76). Additionally, when parental depression was present and the time since depression diagnosis was more than five years, adolescents with parental depression exhibited even poorer subjective health status and higher stress levels. CONCLUSIONS: The study found that adolescents whose parents experienced depression had poorer mental health than those whose parents did not have mental health issues. These findings emphasize the importance of providing support for the mental health of adolescents in families affected by parental depression.

Association between antibiotic use and subsequent risk of prostate cancer: A retrospective cohort study in South Korea.

OBJECTIVES: Several studies suggest that antibiotic use may affect overall cancer incidence, but the association between antibiotics and prostate cancer is still unclear. This retrospective cohort study aimed to assess the association between antibiotics and the risk of prostate cancer. METHODS: A population-based retrospective cohort study was conducted using the Korean National Health Insurance Service (NHIS) database. 1 032 397 individuals were followed up from January 1, 2007, to December 31, 2019. Multivariable Cox hazards regression was utilized to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the risk of prostate cancer according to accumulative days of antibiotic use and the number of antibiotic classes used from 2002 to 2006. RESULTS: Individuals who used antibiotics for 180 or more days had a higher risk of prostate cancer (aHR, 1.46; 95% CI, 1.11-1.91) than those who did not use antibiotics. Also, individuals who used four or more kinds of antibiotics had a higher risk of prostate cancer (aHR, 1.18; 95% CI, 1.07-1.30) than antibiotic non-users. An overall trend was observed among participants who underwent health examinations. CONCLUSIONS: Our findings suggest that long-term use of antibiotics may affect prostate cancer incidence. Further studies are needed to improve understanding of the association between antibiotic use and prostate cancer incidence.

Association of allergic disease with Parkinson's disease: A nationally representative retrospective cohort study.

BACKGROUND: The association of allergic diseases such as allergic rhinitis, asthma, and atopic dermatitis with Parkinson's disease (PD) risk is yet unclear. In the few preceding studies, a short follow-up duration was followed for a relatively small study population, and lifestyle behaviors were not adjusted for. Therefore, there is a need for large-scale observation studies on the association of allergic disease with PD risk after considering lifestyle behaviors. METHODS: The study population consisted of 398,936 participants aged 40 years or older who underwent health screening before 1 January 2005 from the Korean National Health Insurance Service database. Starting from 1 January 2005, all participants were followed up until the date of PD event, death, or 31 December 2019. The adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for the risk of PD were calculated using multivariable Cox proportional hazards regression. RESULTS: Compared to non-allergic disease participants, allergic disease patients had a higher risk for PD (aHR 1.18, 95% CI 1.07-1.30) and especially, allergic rhinitis patients had a higher risk for PD (aHR 1.14, 95% CI 1.00-1.29). Allergic disease was associated with a higher risk for PD (aHR 1.24, 95% CI 1.01-1.52) among participants who were never smokers, did not consume alcohol, and exercised regularly. CONCLUSIONS: Allergic rhinitis was associated with a higher risk for PD compared to participants without allergic rhinitis. This risk-increasing association of allergic rhinitis with PD was preserved even among people with healthy lifestyle behaviors.

Changes in high-density lipoprotein cholesterol with risk of Cardiovascular Disease among initially high-density lipoprotein-high participants.

BACKGROUND: High-density lipoprotein cholesterol's (HDL-C) long-held status as a cardiovascular disease (CVD) preventative has been called into question. Most of the evidence, however, focused on either the risk of death from CVD, or on single time point level of HDL-C. This study aimed to determine the association between changes in HDL-C levels and incident CVD in individuals with high baseline HDL-C levels (≥ 60 mg/dL). METHODS: 77,134 people from the Korea National Health Insurance Service-Health Screening Cohort were followed for 517,515 person-years. Cox proportional hazards regression was used to evaluate the association between change in HDL-C levels and the risk of incident CVD. All participants were followed up until 31 December 2019, CVD, or death. RESULTS: Participants with the greatest increase in their HDL-C levels had higher risks of CVD (adjusted hazard ratio [aHR], 1.15; 95% confidence interval [CI], 1.05-1.25) and CHD (aHR 1.27, CI 1.11-1.46) after adjusting for age, sex, household income, body mass index, hypertension, diabetes mellitus, dyslipidemia, smoking, alcohol consumption, moderate-to-vigorous physical activity, Charlson comorbidity index, and total cholesterol than those with the lowest increase in HDL-C levels. Such association remained significant even among participants with decreased low-density lipoprotein cholesterol (LDL-C) levels for CHD (aHR 1.26, CI 1.03-1.53). CONCLUSIONS: In people with already high HDL-C levels, additional increases in HDL-C levels may be associated with an increased risk of CVD. This finding held true irrespective of the change in their LDL-C levels. Increasing HDL-C levels may lead to unintentionally elevated risk of CVD.

Effect of changes in sleeping behavior on skeletal muscle and fat mass: a retrospective cohort study.

BACKGROUND: An association between sleep behaviors and muscle-fat mass is continuously interesting topic. METHODS: Based on the survey on sleep behaviors (quality and duration), the poor quality of sleep was evaluated when the subject did not feel satisfied after sleep, while the good quality was evaluated as they feel refreshed. A total of 19,770 participants were divided into the four groups according to changes in sleep quality: Good-to-Good (those who continuously maintained good quality), Good-to-Poor (those who reported initial good quality but subsequently reported a poor quality), Poor-to-Poor (those who continuously maintained poor quality), and Poor-to-Good (those who reported improved quality of sleep). As changes in skeletal muscle and fat mass index [kg/m2] were estimated by a validated prediction equation, multiple linear regression was used to calculate adjusted mean (adMean) of muscle and fat mass according to changes in sleep behavior. RESULTS: When sleep duration decreased and quality of sleep deteriorated (from good to poor), fat mass index significantly increased (adMean: 0.087 for the Good-to-Good group and 0.210 for the Good-to-Poor group; p-value = 0.006). On the other hand, as the quality of sleep deteriorated, skeletal muscle mass more decreased despite the maintained sleep duration (adMean: -0.024 for the Good-to-Good group and - 0.049 for the Good-to-Poor group; p-value = 0.009). CONCLUSION: Our results showed that changes in sleep quality and duration affect changes in muscle and fat mass. Thus, we suggest maintaining a good quality of sleep, even if sleep duration is reduced, to preserve muscle mass and inhibit the accumulation of fat.

Exercise Frequency Reduction Is Associated With Higher Risk of Infection in Newly Diagnosed Diabetes: A Nationally Representative Cohort Study.

BACKGROUND: Exercise is an important method to control the progression of diabetes. Since diabetes compromises immune function and increases the risk of infectious diseases, we hypothesized that exercise may affect the risk of infection by its immunoprotective effects. However, population-based cohort studies regarding the association between exercise and the risk of infection are limited, especially regarding changes in exercise frequency. The aim of this study was to determine the association between the change in exercise frequency and the risk of infection among patients with newly diagnosed diabetes. METHODS: Data of 10,023 patients with newly diagnosed diabetes were extracted from the Korean National Health Insurance Service-Health Screening Cohort. Self-reported questionnaires for moderate-to-vigorous physical activity (MVPA) were used to classify changes in exercise frequency between two consecutive two-year periods of health screenings (2009-2010 and 2011-2012). The association between changes in exercise frequency and the risk of infection was evaluated using multivariable Cox proportional-hazards regression. RESULTS: Compared with engaging in ≥ 5 times of MVPA/week during both periods, a radical decrease in MVPA (from ≥ 5 times of MVPA/week to physical inactivity) was associated with a higher risk of pneumonia (adjusted hazard ratio [aHR], 1.60; 95% confidence interval [CI], 1.03-2.48) and upper respiratory tract infection (aHR, 1.15; 95% CI, 1.01-1.31). In addition, a reduction of MVPA from ≥ 5 to < 5 times of MVPA/week was associated with a higher risk of pneumonia (aHR, 1.52; 95% CI, 1.02-2.27), whereas the risk of upper respiratory tract infection was not higher. CONCLUSION: Among patients with newly diagnosed diabetes, a reduction in exercise frequency was related to an increase in the risk of pneumonia. For patients with diabetes, a modest level of physical activity may need to be maintained to reduce the risk of pneumonia.

Validity of fatty liver prediction scores for diagnosis of fatty liver by Fibroscan.

BACKGROUND: The Korea National Health and Nutrition Examination Survey nonalcoholic fatty liver disease (K-NAFLD) score was recently developed with the intent to operationally define nonalcoholic fatty liver disease (NAFLD). However, there remained an external validation that confirmed its diagnostic performance, especially in patients with alcohol consumption or hepatitis virus infection. METHODS: Diagnostic accuracy of the K-NAFLD score was evaluated in a hospital-based cohort consisting of 1388 participants who received Fibroscan®. Multivariate-adjusted logistic regression models and the contrast estimation of receiver operating characteristic curves were used for validation of the K-NAFLD score, fatty liver index (FLI), and hepatic steatosis index (HSI). RESULTS: K-NAFLD-moderate [adjusted odds ratio (aOR) = 2.53, 95% confidence interval (CI): 1.13-5.65] and K-NAFLD-high (aOR = 4.14, 95% CI: 1.69-10.13) groups showed higher risks of fatty liver compared to the K-NAFLD-low group after adjustments for demographic and clinical characteristics, and FLI-moderate and FLI-high groups revealed aORs of 2.05 (95% CI: 1.22-3.43) and 1.51 (95% CI: 0.78-2.90), respectively. In addition, the HSI was less predictive for Fibroscan®-defined fatty liver. Both K-NAFLD and FLI also demonstrated high accuracy in the prediction of fatty liver in patients with alcohol consumption and chronic hepatitis virus infection, and the adjusted area under curve values were comparable between K-NAFLD and FLI. CONCLUSIONS: Externally validation of the K-NAFLD and FLI showed that these scores may be a useful, noninvasive, and non-imaging modality for the identification of fatty liver. In addition, these scores also predicted fatty liver in patients with alcohol consumption and chronic hepatitis virus infection.

Pigmented villonodular synovitis after anterior cruciate ligament reconstruction using active bioprosthetic composite artificial ligament.

Pigmented villonodular synovitis (PVNS) is a proliferative disease that develops in the synovium of joints, especially the knee joints. A 52-year-old man visited our hospital with left knee pain, swelling and symptoms of collapse. Twenty-one years earlier, he had undergone anterior cruciate ligament (ACL) reconstruction using an active bioprosthetic composite (ABC) as an artificial ligament. T1 and T2 weighted magnetic resonance imaging of the knee joint showed rupture of the ABC ligament and low signal intensity of hyperplastic synovium. Arthroscopic total synovectomy without ACL reconstruction was performed and the lesion was histopathologically diagnosed as diffuse PVNS. Clinical outcomes included good pain relief and no recurrence of the disease after 5 years of follow-up.

Comparison of Clinical and Hematologic Factors Associated with Stenosis and Aneurysm Development in Patients with Atherosclerotic Arterial Disease.

BACKGROUND: Atherosclerosis is known to result in individuals with arterial stenosis or occlusion. Alternatively, certain atherosclerotic arteries develop aneurysms. However, there has been no clear explanation regarding the mechanism associated with this alternate clinical presentation. This study aimed to investigate the clinical and hematologic factors that could lead to the development of the different clinical outcomes of stenosis and aneurysm in atherosclerotic arterial disease. METHODS: From March 2016 to January 2018, 219 consecutive atherosclerotic patients, of whom 195 (171 men, 24 women) had stenosis or occlusion and 24 (19 men, 5 women) had aneurysm, were investigated. All patients underwent vascular procedures. Continuous variables studied were age, body mass index, smoking status (pack-years), frequency of alcohol consumption (days), levels of natural anticoagulants (protein C, protein S, and antithrombin III), coagulation-enhancing factors (factor VIII, fibrinogen, and homocysteine), antiphospholipid antibodies (lupus anticoagulant, immunoglobulin [Ig] G/IgM anticardiolipin antibody, and IgG/IgM anti-beta 2 glycoprotein I [anti-ß2GPI]), lipids (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglyceride), and hemoglobin A1c. The investigated nominal variables were sex, diabetes mellitus, and hypertension. RESULTS: A logistic regression analysis of all nominal and continuous variables as independent variables revealed that IgM anticardiolipin antibody was a significant independent factor associated with aneurysm formation in atherosclerotic arterial disease (P = 0.042). CONCLUSIONS: A higher IgM anticardiolipin antibody level may be one of the causative factors behind aneurysm development and may have the clinical potential to be used as a biomarker to predict the development of aneurysms in atherosclerotic arterial disease.

Viral RNA in Blood as Indicator of Severe Outcome in Middle East Respiratory Syndrome Coronavirus Infection.

We evaluated the diagnostic and clinical usefulness of blood specimens to detect Middle East respiratory syndrome coronavirus infection in 21 patients from the 2015 outbreak in South Korea. Viral RNA was detected in blood from 33% of patients at initial diagnosis, and the detection preceded a worse clinical course.

Development of 12 Microsatellite Markers in Dorcus titanus castanicolor (Motschulsky, 1861) (Lucanidae, Coleoptera) from Korea Using Next-Generation Sequencing.

In the present study, we used next-generation sequencing to develop 12 novel microsatellite markers for genetic structural analysis of Dorcus titanus castanicolor (Lucanidae; Coleoptera), a popular pet insect in China, Korea, and Japan. We identified 52,357 microsatellite loci in 339,287,381 bp of genomic sequence and selected 19 of the loci based on their PCR amplification efficiency and polymorphism. The 19 selected markers were then tested for the presence of null alleles and linkage disequilibrium. We did not detect any evidence of null alleles; however, four pairs of loci (DT03 and DT11, DT05 and DT26, DT08 and DT26, DT26 and DT35) exhibited linkage disequilibrium. Thus, we assessed the genetic diversity of a D. titanus castanicolor population from the Daejeon region of Korea (n = 22) using 13 markers. Among them, one marker (DT17) deviated from Hardy-Weinberg equilibrium. Therefore, 12 markers may be useful for further analyzing the genetic diversity of D. titanus castanicolor.

Development of Seven Microsatellite Markers Using Next Generation Sequencing for the Conservation on the Korean Population of Dorcus hopei (E. Saunders, 1854) (Coleoptera, Lucanidae).

We developed microsatellite markers for genetic structural analyses of Dorcus hopei, a stag beetle species, using next generation sequencing and polymerase chain reaction (PCR)-based genotyping for regional populations. A total of 407,070,351 base pairs of genomic DNA containing >4000 microsatellite loci except AT repeats were sequenced. From 76 loci selected for primer design, 27 were polymorphic. Of these 27 markers, 10 were tested on three regional populations: two Chinese (Shichuan and Guangxi) and one Korean (Wanju). Three markers were excluded due to inconsistent amplification, genotyping errors, and Hardy-Weinberg equilibrium (HWE). By multi-locus genotyping, the allele number, observed heterozygosity and polymorphism information content of seven microsatellite loci were ranged 2-10, 0.1333-1.0000, and 0.1228-0.8509, respectively. In an analysis on the genetic differentiation among regional populations including one Japanese population and one cross-breeding population, the individual colored bar-plots showed that both Chinese populations were closer to each other than to the Far East Asian populations. In Far East Asian populations, Wanju and Nirasaki populations could not be distinguished from each other because the frequency of genetic contents was very similar in some individuals of two populations. Moreover, the cross-breeding population contained all patterns of genetic contents shown in Chinese, Korean, and Japanese populations, compared with the genetic content frequency of each regional population. As a result, we examined whether the cross-breeding population might be a hybrid population, and might contain a possibility of interbreeding with Chinese populations in parental generations. Therefore, these markers will be useful for analyses of genetic diversity in populations, genetic relationships between regional populations, genetic structure analyses, and origin tests.

Risk of pulmonary embolism and deep vein thrombosis following COVID-19: a nationwide cohort study.

Recent studies elucidate that coronavirus disease 2019 (COVID-19) patients may face a higher risk of cardiovascular complications. This study aimed to evaluate association of COVID-19 with the risk of pulmonary embolism (PE) or deep vein thrombosis (DVT). This nationwide population-based retrospective cohort study included Korean adult citizens between January 2021 and March 2022 from the Korea Disease Control and Prevention Agency COVID-19 National Health Insurance Service cohort. The Fine and Gray's regression with all-cause death as a competing event was adopted to evaluate PE and DVT risks after COVID-19. This study included a total of 1,601,835 COVID-19 patients and 14,011,285 matched individuals without COVID-19. The risk of PE (adjusted hazard ratio [aHR], 6.25; 95% confidence interval [CI], 3.67-10.66; p < 0.001) and DVT (aHR, 3.05; 95% CI, 1.75-5.29; p < 0.001) was higher in COVID-19 group in individuals without complete COVID-19 vaccination. In addition, individuals with complete COVID-19 vaccination still had a higher risk of COVID-19-related PE (aHR, 1.48; 95% CI, 1.15-1.88; p < 0.001). However, COVID-19 was not a significant risk factor for DVT among those with complete COVID-19 vaccination. COVID-19 was identified as an independent factor that elevated PE and DVT risks, especially for individuals without complete COVID-19 vaccination.

Survival dynamics of stick insect and the impact of environmental factors on natural fungal infection during the rainy season.

Phasmatodea, commonly known as stick insects, are recognized as noteworthy pests globally, impacting agriculture and forest ecosystems. Among them, the outbreak of Ramulus mikado has emerged as a notable concern in East Asian forests. Recently, Metarhizium phasmatodeae has been identified as utilizing stick insects as hosts. We have observed evidence of this entomopathogenic fungus infecting stick insects. Given the increase in these occurrences during the rainy period, this study investigated the relationship between the survival of R. mikado and the M. phasmatodeae infection during the rainy seasons of 2022 and 2023. We collected stick insects in two representative forests of the Republic of Korea and examined insect survival, fungal infection, and various environmental factors. No infections were detected in specimens collected in June before the rainy season, but from July onwards, both the mortality of R. mikado and the fungal infection substantially increased. By the last sampling date of each year, 75% (2022), 71.4% (2023) of the specimens were infected, and over 90% of the total individuals succumbed as a result. Fungi isolated from deceased R. mikado were successfully identified as M. phasmatodeae using morphological and taxonomic approaches. Various statistical analyses, including principal component analysis and modeling, revealed a robust association between fungal infection and the survival of stick insects. The results highlight the correlation between mass deaths of stick insects and fungal infection, particularly during the summer rainy season. These findings offer valuable insights for forecasting R. mikado population in the upcoming year and developing effective pest control strategies.

Protective effect of vaccination on the risk of cardiovascular disease after SARS-CoV-2 infection.

OBJECTIVE: This study investigated the incidence of CVDs after COVID-19. METHODS: Data for 2,146,130 infected people were collected, including the vaccination status. COVID-19 patients were classified according to the number of the received vaccine doses: no, first, second, and ≥ third. To evaluate the short-term risk of CVDs after infection, adjusted odds ratios (aOR) and 95% confidence intervals (CIs) were calculated by multivariable logistic regression analysis after adjustments for covariates. RESULTS: Compared to non-infected people, aORs [95% CIs; p value] for CVDs within a month after infection were 2.80 [2.64-2.97; < 0.001] in overall infected people and 4.62 [4.23-5.05; < 0.001], 4.20 [3.45-5.11; < 0.001], 2.79 [2.55-3.05; < 0.001], and 2.07 [1.91-2.24; < 0.001] in those who were infected after receiving no, first, second, and ≥ third vaccine doses, respectively. Among participants who received second doses of vaccine prior to contracting COVID-19, the aOR in those vaccinated with only the mRNA-based vaccine (BNT162b2 and mRNA-1273; Reference) was lower than those vaccinated with the virus-derived vaccine (ChAdOx1 nCov-19 and AD26.COV2-S; aOR 1.25 [1.06-1.48; < 0.01]). CONCLUSION: Although COVID-19 increased the CVD risk, the inverse association in the risk of CVDs according to vaccine doses was significant in a dose-response manner. Our findings suggest that ≥ second doses of the COVID-19 vaccine prevent the risk of CVDs after SARS-CoV-2 infection.

Association Between Antibiotic Exposure and Thyroid Cancer: A Nationwide Cohort Study in South Korea.

Background: Although recent studies have introduced antibiotics as a potential risk factor for thyroid cancer, further studies are necessary. We examined the association between long-term antibiotic usage and thyroid cancer risk. Methods: This nationwide cohort study investigated 9,804,481 individuals aged 20 years or older who participated in health screening (2005-2006) with follow-up ending on December 31, 2019, using the Korean National Health Insurance Service database. Multivariable Cox proportional hazards regression was used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for thyroid cancer risk according to the cumulative days of antibiotic prescription and the number of antibiotic classes, respectively. A 1:1 propensity score (PS) matching was also performed for analysis. Results: Compared with nonusers of antibiotics, participants prescribed ≥365 days of antibiotics showed an increased risk of thyroid cancer (aHR, 1.71; CI, 1.66-1.78) after adjusting for covariates including age, smoking status, comorbidities including thyroid-related diseases, and the number of head and neck computed tomography scans. Participants prescribed ≥365 days of antibiotics also had a significantly increased risk of thyroid cancer (aHR, 1.37; CI, 1.34-1.40) compared with participants prescribed 1-14 days of antibiotics. Association remained significant in the 1:1 PS-matched cohort. Moreover, compared with nonusers of antibiotics, the 5 or more antibiotic class user group had a higher thyroid cancer risk (aHR, 1.71; CI, 1.65-1.78). Conclusions: Long-term antibiotic prescriptions and an increasing number of antibiotic classes may be associated with a higher risk of thyroid cancer in a duration-dependent manner. The effects of long-term antibiotic exposure on thyroid cancer should be further investigated.

Evolutionary changes in metabolic dysfunction-associated steatotic liver disease and risk of hepatocellular carcinoma: A nationwide cohort study.

BACKGROUND/AIMS: To determine the association between evolutionary changes in metabolic dysfunction-associated steatotic liver disease (MASLD) status and the risk of hepatocellular carcinoma (HCC) in a nationwide population-based cohort. METHODS: Information on study participants was derived from the Korea National Health Insurance Service database. The study population consisted of 5,080,410 participants who underwent two consecutive biennial health screenings between 2009 and 2012. All participants were followed up until HCC, death, or 31 December 2020. The association of evolutionary changes in MASLD status, as assessed by the fatty liver index and cardiometabolic risk factors, including persistent non-MASLD, resolved MASLD, incident MASLD, and persistent MASLD, with HCC risk was evaluated using multivariable-adjusted Cox proportional hazards regression. RESULTS: Among the 5,080,410 participants with 39,910,331 person-years of follow-up, 4,801 participants developed HCC. The incidence of HCC in participants with resolved, incident, and persistent MASLD was approximately 2.2-, 2.3-, and 4.7-fold higher, respectively, than that in those with persistent non-MASLD among the Korean adult population. When stratifying the participants according to the evolutionary change in MASLD status, persistent (adjusted hazard ratio [aHR], 2.94; 95% confidence interval [CI], 2.68-3.21; P<0.001), incident (aHR, 1.85; 95% CI, 1.63-2.10; P<0.001), and resolved MASLD (aHR, 1.33; 95% CI, 1.18-1.50; P<0.001) had an increased risk of HCC compared to persistent non-MASLD. CONCLUSION: The evolutionary changes in MASLD were associated with the differential risk of HCC independent of metabolic risk factors and concomitant medications, providing additional information on the risk of HCC stratification in patients with MASLD.