Novel Genetic Variants Associated with Chronic Kidney Disease Progression.

SIGNIFICANCE STATEMENT: eGFR slope has been used as a surrogate outcome for progression of CKD. However, genetic markers associated with eGFR slope among patients with CKD were unknown. We aimed to identify genetic susceptibility loci associated with eGFR slope. A two-phase genome-wide association study identified single nucleotide polymorphisms (SNPs) in TPPP and FAT1-LINC02374 , and 22 of them were used to derive polygenic risk scores that mark the decline of eGFR by disrupting binding of nearby transcription factors. This work is the first to identify the impact of TPPP and FAT1-LINC02374 on CKD progression, providing predictive markers for the decline of eGFR in patients with CKD. BACKGROUND: The incidence of CKD is associated with genetic factors. However, genetic markers associated with the progression of CKD have not been fully elucidated. METHODS: We conducted a genome-wide association study among 1738 patients with CKD, mainly from the KoreaN cohort study for Outcomes in patients With CKD. The outcome was eGFR slope. We performed a replication study for discovered single nucleotide polymorphisms (SNPs) with P <10 -6 in 2498 patients with CKD from the Chronic Renal Insufficiency Cohort study. Several expression quantitative trait loci (eQTL) studies, pathway enrichment analyses, exploration of epigenetic architecture, and predicting disruption of transcription factor (TF) binding sites explored potential biological implications of the loci. We developed and evaluated the effect of polygenic risk scores (PRS) on incident CKD outcomes. RESULTS: SNPs in two novel loci, TPPP and FAT1-LINC02374 , were replicated (rs59402340 in TPPP , Pdiscovery =7.11×10 -7 , PCRIC =8.13×10 -4 , Pmeta =7.23×10 -8 ; rs28629773 in FAT1-LINC02374 , Pdiscovery =6.08×10 -7 , PCRIC =4.33×10 -2 , Pmeta =1.87×10 -7 ). The eQTL studies revealed that the replicated SNPs regulated the expression level of nearby genes associated with kidney function. Furthermore, these SNPs were near gene enhancer regions and predicted to disrupt the binding of TFs. PRS based on the independently significant top 22 SNPs were significantly associated with CKD outcomes. CONCLUSIONS: This study demonstrates that SNP markers in the TPPP and FAT1-LINC02374 loci could be predictive markers for the decline of eGFR in patients with CKD.

Intrahepatic mass-forming cholangiocarcinoma: prognostic value of preoperative gadoxetic acid-enhanced MRI.

OBJECTIVES: To assess whether gadoxetic acid-enhanced MRI could be used as a prognostic factor for intrahepatic mass-forming cholangiocarcinomas (IMCCs). METHODS: Forty-one patients with pathologically proven IMCCs who underwent preoperative gadoxetic acid-enhanced MRI were included. The signal intensity of the IMCCs on hepatobiliary phase (HBP) MRI was qualitatively analyzed by two radiologists, and categorized into intermediate or hypointense groups. Analysis of clinicopathological prognostic factors and correlations of imaging and histology were also performed. Survival time and time to recurrence (TTR) were analyzed. RESULTS: Of the 41 IMCCs, 23 were in the intermediate group and 18 were in the hypointense group on HBP MRI. IMCCs in the intermediate group were associated with shorter survival time (P = 0.048) and TTR (P = 0.002) than the IMCCs of the hypointense group. Only the intermediate group on HBP MRI had a significantly shorter TTR on multivariate analysis (P = 0.012). The IMCCs of the intermediate group showed a tendency for more abundant tumour fibrous stroma than those of the hypointense group (P = 0.027). CONCLUSIONS: The enhancement of IMCCs on HBP gadoxetic acid-enhanced MRI appears to correlate with tumour aggressiveness and outcomes due to the tumour fibrous stromal component. Thus, HBP images could be a useful prognostic factor for IMCCs after surgery. KEY POINTS: • The enhancement of IMCCs on HBP correlates with the tumour fibrous stroma. • The enhancement of IMCCs on HBP MRI appears to correlate with prognosis. • Gadoxetic acid-enhanced MRI is helpful for predicting prognosis of IMCCs after surgery.

Contemporary Patterns and Underlying Causes of Vitrectomy in Pediatric and Adolescent Patients: A Nationwide, Population-Based Analysis.

PURPOSE: We determined the incidence, etiology, and longitudinal trends of vitreoretinal diseases necessitating pars plana vitrectomy (PPV) in the pediatric and adolescent population. DESIGN: Nationwide, population-based cohort study. METHODS: This study utilized data extracted from the Korean National Health Claims database spanning from 2009 to 2020. All pediatric and adolescent patients (under 20 years of age) who underwent PPV across the Korean population were included. The cumulative incidence of PPV was estimated from 2009 to 2020, with 2009 to 2011 as the washout period. The annual trends of PPV incidence, the proportion of each etiology, and comorbidity were estimated based on sex and specific age groups. RESULTS: In total, 1913 patients, including 83 infants, 746 pediatric patients, and 1084 adolescents, were newly identified as having undergone PPV surgery. The cumulative incidence of PPV surgery per 100,000 individuals was 21.42 (95% CI, 21.41-21.43). The rate of PPV was 2.4 times higher for males than females, and the rate of trauma as a comorbidity was also higher for males than females (13.1% vs 4.8%). Among males aged 5 years and older, the incidence of PPV nearly halved from 2011 to 2020. Among the primary etiologies, ROP had the highest rate (72%) in infants (under 1 year), while RD was most common (63%) in individuals aged 5 to 19 years. Myopia was present in 30.3% of patients, and atopic dermatitis was present in 31.8% of all patients. CONCLUSION: The primary etiologies underlying the need for PPV in the pediatric and adolescent populations vary by sex and age group. The incidence of PPV continues to decline in the adolescent population. Therefore, tailored patient education and age-specific etiological examination are recommended.

Physical activity and mental health trends in Korean adolescents: Analyzing the impact of the COVID-19 pandemic from 2018 to 2022.

Objective: Mental health significantly affects the physical and emotional development of adolescents. The aim of the current study was to examine how physical activity (PA) and mental health among Korean adolescents changed before and after the start of the COVID-19 pandemic. Methods: We used comparative cross-sectional methods, gathering information from the Korea Disease Control and Prevention Agency databases and conducting Chi-square testing and correlation analysis for evaluation. Results: The findings indicate that before and during the pandemic, participation in both moderate- and high-intensity PA, as well as strength training, mitigated stress, depression, and suicidal ideation. Furthermore, the findings confirm the beneficial effects of various physical activities on mental well-being. Conclusions: These insights emphasize the vital role of regular PA in improving mental health among adolescents, particularly during a health crisis such as the pandemic.

Cancer Risks of Patients with Graves' Disease Who Received Antithyroid Drugs as Initial Treatment: A Nationwide Population-Based Analysis.

Background: Population-based studies that examine the associations between hyperthyroidism and cancer risk have yielded inconsistent results. It remains unclear whether the risks of different cancers increase in patients with Graves' disease (GD) who received antithyroid drugs (ATDs) as initial treatment. We aimed to determine whether cancer risk increases in patients with GD, compared with controls. Methods: This nationwide retrospective cohort study utilized data from the National Health Information Database of South Korea. We included 29,502 patients aged >20 years with GD, who received ATDs as initial treatment, and 57,173 age- and sex-matched controls. The primary outcome was the incidence of various types of cancers. Hazard ratios (HRs) with confidence intervals (CIs) for cancer risk were estimated using Cox proportional hazards models. We also analyzed HR by follow-up period since the diagnosis of GD, accounting for surveillance effect. Results: The risk of biliary tract and pancreatic cancers (HR: 1.41, CI: 1.24-1.60), thyroid cancer (HR: 15.51, CI: 12.29-19.57), prostate cancer (HR: 1.48, CI: 1.28-1.71), and ovarian cancer (HR: 1.31, CI: 1.13-1.52) was elevated in the GD group than in the control group even after the first year of follow-up was excluded. The increased risk of these cancers persisted after a follow-up period of more than 5 years. The risk of thyroid cancer in patients with GD was higher during the initial follow-up period (1 to <2 years) (HR: 19.35, CI: 7.66-48.87) compared with that in the follow-up period exceeding 2 years. The cancer risk estimates remained significant after excluding patients with GD who underwent subsequent radioactive iodine therapy. Conclusion: In this large-scale population-based study, GD was associated with increased risks of biliary tract and pancreatic, prostate, ovarian, and thyroid cancers. The increased risk of thyroid cancer, particularly during the initial follow-up period, may be a surveillance effect.

A Comparison of Green, Delta, and Monte Carlo Methods to Select an Optimal Approach for Calculating the 95% Confidence Interval of the Population-attributable Fraction: Guidance for Epidemiological Research.

OBJECTIVES: This study aimed to compare the Delta, Greenland, and Monte Carlo methods for estimating 95% confidence intervals (CIs) of the population-attributable fraction (PAF). The objectives were to identify the optimal method and to determine the influence of primary parameters on PAF calculations. METHODS: A dataset was simulated using hypothetical values for primary parameters (population, relative risk [RR], prevalence, and variance of the beta estimator ) involved in PAF calculations. Three methods (Delta, Greenland, and Monte Carlo) were used to estimate the 95% CIs of the PAFs. Perturbation analysis was performed to assess the sensitivity of the PAF to changes in these parameters. An R Shiny application, the "GDM-PAF CI Explorer," was developed to facilitate the analysis and visualization of these computations. RESULTS: No significant differences were observed among the 3 methods when both the RR and p-value were low. The Delta method performed well under conditions of low prevalence or minimal RR, while Greenland's method was effective in scenarios with high prevalence. Meanwhile, the Monte Carlo method calculated 95% CIs of PAFs that were stable overall, though it required intensive computational resources. In a novel approach that utilized perturbation for sensitivity analysis, was identified as the most influential parameter in the estimation of CIs. CONCLUSIONS: This study emphasizes the necessity of a careful approach for comparing 95% CI estimation methods for PAFs and selecting the method that best suits the context. It provides practical guidelines to researchers to increase the reliability and accuracy of epidemiological studies.

Selenium levels and their association with thyroid autoimmunity and severe preeclampsia in pregnancy: Insights from a prospective ideal breast milk cohort study.

Objective: This study aimed to assess selenium status in South Korean pregnant women and its impact on maternal thyroid function and pregnancy outcomes. Methods: 'Ideal Breast Milk (IBM) Cohort Study' included 367 pregnant women out of 442 participants and categorized into three groups based on plasma selenium levels: deficient (< 70 µg/L), suboptimal (70-99 µg/L), and optimal (≥ 100 µg/L). During the second or third trimester, various blood parameters, including selenium, thyroid-stimulating hormone, free T4, free T3, and anti-thyroid peroxidase antibody levels, were measured. Thyroid parenchymal echogenicity was assessed as another surrogate marker for thyroid autoimmunity using ultrasonography. Results: The median plasma selenium was 98.8 (range: 46.7-206.4) µg/L, and 30 individuals (8%) were categorized as deficient, while 164 (45%) were classified in the suboptimal group. Selenium deficiency was associated with markers of autoimmune thyroiditis, including positive anti-thyroid peroxidase antibody results (13.3 (deficient) vs 4.6 (optimal) %, P = 0.031) and thyroid parenchymal heterogeneity on ultrasound (33.3 (deficient) vs 14.6 (suboptimal) vs 17.3 (optimal) %, P = 0.042), independently of gestational age. The incidence of severe preeclampsia was higher in the group not taking selenium supplements, particularly among those with twin pregnancies, compared to the group taking selenium supplements (0 (selenium supplement) vs 9.0 (no supplement) %, P = 0.015). Conclusion: Pregnant women experience mild selenium deficiency, which can lead to significant health issues including maternal thyroid autoimmunity and obstetrical complications during pregnancy. Guidelines for appropriate selenium intake according to the stage of pregnancy and the number of fetuses are needed.

Active Surveillance for Low-Risk Thyroid Cancers: A Review of Current Practice Guidelines.

The indolent nature and favorable outcomes associated with papillary thyroid microcarcinoma have prompted numerous prospective studies on active surveillance (AS) and its adoption as an alternative to immediate surgery in managing low-risk thyroid cancer. This article reviews the current status of AS, as outlined in various international practice guidelines. AS is typically recommended for tumors that measure 1 cm or less in diameter and do not exhibit aggressive subtypes on cytology, extrathyroidal extension, lymph node metastasis, or distant metastasis. To determine the most appropriate candidates for AS, factors such as tumor size, location, multiplicity, and ultrasound findings are considered, along with patient characteristics like medical condition, age, and family history. Moreover, shared decision-making, which includes patient-reported outcomes such as quality of life and cost-effectiveness, is essential. During AS, patients undergo regular ultrasound examinations to monitor for signs of disease progression, including tumor growth, extrathyroidal extension, or lymph node metastasis. In conclusion, while AS is a feasible and reliable approach for managing lowrisk thyroid cancer, it requires careful patient selection, effective communication for shared decision-making, standardized follow-up protocols, and a clear definition of disease progression.

Sex-specific Associations between Body Mass Index and Thyroid Cancer Incidence among Korean Adults.

BACKGROUND: The potential differences by sex in the association between body mass index (BMI) and thyroid cancer risk remain unconfirmed. METHODS: Data from the National Health Insurance Service-National Health Screening Cohort (NHIS-HEALS; 2002-2015; population size = 510,619) and the Korean Multi-center Cancer Cohort (KMCC) data (1993-2015; population size = 19,026) were used. We constructed Cox regression models, adjusted for potential confounders, to evaluate the association between BMI and thyroid cancer incidence in each cohort, and assessed the consistency of the results. RESULTS: In the NHIS-HEALS, 1,351 and 4,609 incident thyroid cancer cases occurred during the follow-up among men and women, respectively. Compared with BMI of 18.5-22.9 kg/m2, BMI of 23.0-24.9 [no. of cases = 410; HR, 1.25; 95% confidence interval (CI), 1.08-1.44], 25.0-29.9 (no. of cases = 522; HR, 1.32; 95% CI, 1.15-1.51), and ≥30.0 kg/m2 (no. of cases = 48; HR, 1.93; 95% CI, 1.42-2.61) were associated with an increased risk of incident thyroid cancer among males. Among females, BMI of 23.0-24.9 (no. of cases = 1,300; HR, 1.17; 95% CI, 1.09-1.26) and 25.0-29.9 (no. of cases = 1,406; HR, 1.20; 95% CI, 1.11-1.29) were associated with incident thyroid cancer. The analyses using the KMCC demonstrated results consistent with wider CIs. CONCLUSIONS: Sex differences in the associations between BMI and thyroid cancer incidence were observed in Korean cohorts. IMPACT: BMI <23 kg/m2 may help prevent incident thyroid cancer, especially among men.

Clinical traits and systemic risks of familial diabetes mellitus according to age of onset and quantity: an analysis of data from the community-based KoGES cohort study.

OBJECTIVES: The aim of this study was to clarify the clinical trait of familial diabetes mellitus (DM) by analyzing participants' risk of DM according to the age of DM onset in parents and siblings, and to evaluate individuals' risk of DM-associated cardiometabolic diseases. METHODS: Altogether, 211,173 participants aged ≥40 years from the Korean Genome and Epidemiology Study were included in this study. The participants were divided into groups based on the number (1 or 2 relatives) and age of onset (no DM and early, common, or late onset) of familial DM. Participants' risk of DM was assessed using a Cox regression model with hazard ratios and 95% confidence intervals (CIs). A logistic regression model with odds ratios was used to evaluate associations among the participants' likelihood of acquiring cardiometabolic diseases such as hypertension, chronic kidney disease (CKD), and cardiovascular disease. RESULTS: The risk of developing DM was 2.02-fold (95% CI, 1.88 to 2.18) and 2.88-fold (95% CI, 2.50 to 3.33) higher, respectively, in participants with 1 and 2 family members diagnosed with familial DM. It was 2.72-fold (95% CI, 2.03 to 3.66) higher in those with early-onset familial DM. In the early-onset group, the respective risks of hypertension and CKD were 1.87-fold (95% CI, 1.37 to 2.55) and 4.31-fold (95% CI, 2.55 to 7.27) higher than in the control group. CONCLUSIONS: The risk of DM and related cardiometabolic diseases was positively associated with the number of family members diagnosed with DM and an early diagnosis in family members with DM.

Gadoxetic acid-enhanced MRI findings of early hepatocellular carcinoma as defined by new histologic criteria.

PURPOSE: To describe the imaging features of early hepatocellular carcinoma (HCC) on gadoxetic acid-enhanced MRI (Gd-EOB-MRI) in comparison with multidetector computed tomography (MDCT) examinations. MATERIALS AND METHODS: We analyzed imaging findings of 19 pathologically proven early HCC lesions in 15 patients who underwent both MDCT and Gd-EOB-MRI at 3.0 Tesla (T) units before surgery. MRI included in-phase and out-of-phase T1-weighted dual-echo gradient-recalled-echo sequences, dynamic T1-weighted images before and after bolus injection of gadoxetic acid disodium, fat-saturated T2-weighted fast spin-echo sequences, and T1-weighted hepatobiliary phase images 20 min after contrast injection. Two radiologists retrospectively evaluated the signal intensities and enhancement features on MRI and MDCT. RESULTS: None of the lesions displayed arterial enhancement and washout on MDCT. On Gd-EOB-MRI, six (32%) lesions showed T2-hyperintensity, five (26%) lesions showed signal drop on opposed-phase. Three lesions (16%) showed arterial enhancement and washout. Twelve (63%), 13 (68%), and 15 (79%) lesions were hypointense on hepatic venous, equilibrium, and hepatobiliary phase, respectively. CONCLUSION: Most early HCCs did not show arterial enhancement and washout pattern on both MDCT and Gd-EOB-MRI. Gd-EOB-MRI may provide several ancillary findings for diagnosis of early HCC such as decreased hepatobiliary uptake, T2 hyperintensity and signal drop in opposed phase.

Semiconductor Work, Leukemia, and Cancer Risk: A Systematic Review and Meta-Analysis.

BACKGROUND: With the development of the semiconductor industry over the past 60 years, various occupational diseases have been reported to coincide with rapid industrial growth. Among these occupational diseases, the association between semiconductor work and cancers, including leukemia, remains controversial. Therefore, this systematic review and meta-analysis assesses the associations between semiconductor work, leukemia, and cancer risk. METHODS: The core research databases, including PubMed, were screened for studies published until 31 July 2022. All eligible studies assessed cancer risk among workers in the semiconductor industry. RESULTS: Nine studies were selected after a literature review. The employment period of semiconductor workers in each study was between 1965 and 2009. Semiconductor work was not significantly associated with the risk of leukemia (Relative Risk [RR], 1.02; 95% Confidence Interval [CI], 0.74-1.41) or cancer (RR, 1.00; 95% CI, 0.93-1.07). CONCLUSION: In this meta-analysis, semiconductor work was not significantly associated with leukemia or cancer risk. Internal comparisons, such as non-fab workers, quality of the study, employment period, and healthy worker effect, should be considered for interpretation. Furthermore, a prospective cohort study based on overall semiconductor workers in the industry could be useful to assess occupational disease risk as a mandatory component of health assessment.

Social and Policy Determinants of COVID-19 Infection Across 23 Countries: An Ecological Study.

OBJECTIVES: This study aimed to identify the social and policy determinants of coronavirus disease 2019 (COVID-19) infection across 23 countries. METHODS: COVID-19 indicators (incidence, mortality, and fatality) for each country were calculated by direct and indirect standardization. Multivariable regression analyses were used to identify the social and policy determinants of COVID-19 infection. RESULTS: A higher number of doctors per population was related to lower incidence, mortality, and fatality rates of COVID-19 in 23 countries (ß=-0.672, -0.445, and -0.564, respectively). The number of nurses/midwives per population was associated with lower mortality and fatality rates of COVID-19 in 23 countries (ß=-0.215 and -0.372, respectively). Strengthening of policy restriction indicators, such as restrictions of public gatherings, was related to lower COVID-19 incidence (ß=-0.423). A national Bacillus Calmette-Guérin vaccination policy conducted among special groups or in the past was associated with a higher incidence of COVID-19 in 23 countries (ß=0.341). The proportion of the elderly population (aged over 70 years) was related to higher mortality and fatality rates (ß=0.209 and 0.350, respectively), and income support was associated with mortality and fatality rates (ß=-0.362 and -0.449, respectively). CONCLUSIONS: These findings do not imply causality because this was a country-based correlation study. However, COVID-19 transmission can be influenced by social and policy determinants such as integrated health systems and policy responses to COVID-19. Various social and policy determinants should be considered when planning responses to COVID-19.

Changes in Physical Activity and Health Indicators among Koreans during the COVID-19 Pandemic: Comparison between 2019 and 2020.

This study aimed to compare the changes in physical activity (PA), chronic disease, and mental health indicators of Koreans before and after the COVID-19 outbreak, using raw data from more than 400,000 representative samples from the 2019-2020 Community Health Survey by the Korea Centers for Disease Control and Prevention, and to explore the correlations among them. We used two-way ANOVA to analyze changes and differences in PA and obesity levels. We assessed the influence of gender and recurrent PA using chi-square tests for mental health status and chronic disease. Finally, we performed a correlation analysis to determine the relationships among PA days, mental health, and chronic disease. The results showed that, compared to the levels before the COVID-19 period, moderate-intensity (Days: 1.415~1.217; Time: 114.688~107.321) and high-intensity (Days: 0.798~0.671; Time: 112.866~106.110) PA significantly decreased in Koreans during the COVID-19 period, while low-intensity (Time: 60.305~61.735) PA increased. Before and during the COVID-19 period, men (18,436 (8.1%)~16,124 (7.0%)) performed PA more regularly than women (13,207 (5.8%)~9382 (4.1%)). Compared to the number of regular PA participants before the COVID-19 period, regular PA participants (male, female) decreased from 31,643 (13.8%) to 25,506 (11.1%) during the COVID-19 period. Compared with the levels before the COVID-19 period, the experience rates of stress (3.1%~2.6%), depression (0.8%~0.6%), HBP (3.0%~2.2%), and diabetes (1.2%~0.9%) significantly changed under different levels of conventional PA intervention. In addition, the obesity rate during the COVID-19 period (23.957) was higher than it was before COVID-19 (23.477). During the COVID-19 period, the PA of Koreans was greatly restricted, but low-intensity PA was maintained and increased. PA is an effective activity for maintaining mental health and for preventing and reducing chronic diseases. Recommendations for appropriate intensity or a combination of high-, moderate-, and low-intensity PA should be based on the health status of Koreans to help them maintain mental health and to reduce the risk of chronic diseases during COVID-19 social distancing.

Biological Assessment of Potential Exposure to Occupational Substances in Current Semiconductor Workers with at Least 5 Years of Employment.

BACKGROUND: this study aimed to conduct a biological assessment of the potential exposure to carcinogenic substances in current semiconductor workers. METHODS: A cross-sectional study was conducted on 306 semiconductor workers. The assessed biomarkers were as follows: (benzene) urine S-phenylmercapturic, trans,trans-muconic acid, blood benzene; (trichloroethylene) urine trichloroacetic acid; (2-ethoxyethanol) 2-ethoxyacetic acid; (arsine) urine arsenic3+, arsenic5+, monomethylarsonic, dimethylarsinic acid, arsenobetaine; (shift work) 6-hydroxymelatonin; (smoking) cotinine, and (radiation). The detection rate of these materials is defined as more than the biological exposure index (BEI) or the previous reference value. RESULTS: Some workers exposed to trans,trans-muconic acid, trichloroacetic acid, and arsenic5+ showed high BEI levels. Generally, there was no difference according to job categories, and workers were suspected to be exposed to other sources. The melatonin concentration tended to decrease when working at night, and cotinine was identified as an excellent surrogate marker for smoking. In the case of radiation exposure, there was no significant difference in the number of stable chromosome translocation in 19 semiconductor workers. Their estimated radiation exposure level was below the limit of detection (LOD) or near the LOD level. CONCLUSION: In this study, most carcinogens were below the BEI level, but verification through re-measurement was needed for workers who were identified to have a high BEI level. For continuous monitoring, a prospective cohort is necessary to deal with the healthy worker effect and assess additional materials.

Health Status, Health-Related Factors and Work Environment in Korean Semiconductor Workers between 1984-2012: A Qualitative Study and a Cross-Sectional Study.

BACKGROUND: The environment of semiconductor facilities and exposure status has undergone changes. To identify changes in the work environment, health status, and risk factors, a qualitative and cross-sectional study was conducted. METHODS: For the qualitative study, 38 current and retired workers who worked for at least 10-years were studied; for the cross-sectional study, 306 current workers who worked for at least 5-years based on JEM strata from Samsung Electronics were selected. Participants were asked about occupational history, cancer-relating risk factors during the working period, medical history, dietary habits for the past year, and hematological cancer-relating infection. RESULTS: In the qualitative study, fabrication workers reported bladder cystitis, dermatitis in hands, gastritis/ulcer, and dry eye as frequent symptoms during work environment changes (manual to automatic process). In the cross-sectional study, there were no abnormal findings for infection biomarkers related to hematological cancer and spontaneous abortion, and their general health status was no different from the general population. Also, questionnaire feasibility was evaluated for the applicability in the prospective cohort. CONCLUSION: Current semiconductor workers' health status was good compared to other populations. For lifelong health assessment, a cohort study is needed which considers health worker effects and current environments.

Identifying Genetic Variants and Metabolites Associated with Rapid Estimated Glomerular Filtration Rate Decline in Korea Based on Genome-Metabolomic Integrative Analysis.

Identifying the predisposing factors to chronic or end-stage kidney disease is essential to preventing or slowing kidney function decline. Therefore, here, we investigated the genetic variants related to a rapid decline in the estimated glomerular filtration rate (eGFR) (i.e., a loss of >5 mL/min/1.73 m2 per year) and verified the relationships between variant-related diseases and metabolic pathway signaling in patients with chronic kidney disease. We conducted a genome-wide association study that included participants with diabetes, hypertension, and rapid eGFR decline from two Korean data sources (N = 115 and 69 for the discovery and the validation cohorts, respectively). We identified a novel susceptibility locus: 4q32.3 (rs10009742 in the MARCHF1 gene, beta = −3.540, P = 4.11 × 10−8). Fine-mapping revealed 19 credible, causal single-nucleotide polymorphisms, including rs10009742. The pimelylcarnitine and octadecenoyl carnitine serum concentrations were associated with rs10009742 (beta = 0.030, P = 7.10 × 10−5, false discovery rate (FDR) = 0.01; beta = 0.167, P = 8.11 × 10−4, FDR = 0.08). Our results suggest that MARCHF1 is associated with a rapid eGFR decline in patients with hypertension and diabetes. Furthermore, MARCHF1 affects the pimelylcarnitine metabolite concentration, which may mediate chronic kidney disease progression by inducing oxidative stress in the endoplasmic reticulum.

Projection of Cancer Incidence and Mortality From 2020 to 2035 in the Korean Population Aged 20 Years and Older.

OBJECTIVES: This study aimed to identify the current patterns of cancer incidence and estimate the projected cancer incidence and mortality between 2020 and 2035 in Korea. METHODS: Data on cancer incidence cases were extracted from the Korean Statistical Information Service from 2000 to 2017, and data on cancer-related deaths were extracted from the National Cancer Center from 2000 to 2018. Cancer cases and deaths were classified according to the International Classification of Diseases, 10th edition. For the current patterns of cancer incidence, age-standardized incidence rates (ASIRs) and age-standardized mortality rates were investigated using the 2000 mid-year estimated population aged over 20 years and older. A joinpoint regression model was used to determine the 2020 to 2035 trends in cancer. RESULTS: Overall, cancer cases were predicted to increase from 265 299 in 2020 to 474 085 in 2035 (growth rate: 1.8%). The greatest increase in the ASIR was projected for prostate cancer among male (7.84 vs. 189.53 per 100 000 people) and breast cancer among female (34.17 vs. 238.45 per 100 000 people) from 2000 to 2035. Overall cancer deaths were projected to increase from 81 717 in 2020 to 95 845 in 2035 (average annual growth rate: 1.2%). Although most cancer mortality rates were projected to decrease, those of breast, pancreatic, and ovarian cancer among female were projected to increase until 2035. CONCLUSIONS: These up-to-date projections of cancer incidence and mortality in the Korean population may be a significant resource for implementing cancer-related regulations or developing cancer treatments.

Active Surveillance Versus Immediate Surgery for Low-Risk Papillary Thyroid Microcarcinoma Patients in South Korea: A Cost-Minimization Analysis from the MAeSTro Study.

Background: Active surveillance (AS) has been established as an alternative to immediate surgery for low-risk papillary thyroid microcarcinoma (PTMC). Nonetheless, it remains difficult to decide between AS and immediate surgery, since limited objective evidence exists regarding risks and benefits. The aim of study is to compare the cumulative costs of AS and immediate surgery. Methods: To estimate cumulative costs, a hypothetical model is simulated based on the Multicenter Prospective Cohort Study of Active Surveillance on Papillary Thyroid Micro-Carcinoma (MAeSTro) study, a multicenter prospective cohort study of AS for PTMC. Direct and indirect costs are estimated from diagnosis to the treatment decision and follow-up for 10 years and a longer period. In the case of the scenarios, AS, AS to surgery due to changing their mind, and lobectomy (analyzed regardless of levothyroxine [LT4] treatment, as well as subdivided into lobectomy/LT4[-] and lobectomy/LT4[+]) are considered. A sensitivity analysis is performed using different discount rates to address uncertainties in future time costs. To compare the cumulative costs, we referred to previous research conducted in Hong Kong, the United States, and Japan. Results: The initial cost of AS is estimated to be 5.6 times lower than that of lobectomy (regardless of LT4 use), while the 10-year cumulative costs of AS ($2545) and lobectomy regardless of LT4 ($3045) are similar under a discount rate of 3%. However, in the long-term follow-up period, immediate surgery is going to be estimated more economical than AS. The costs of the two management approaches are similar in Hong Kong, but substantially different in the United States and Japan, implying that it could be affected by each country's national health insurance coverage and the thyroid ultrasound interval during follow-up. Conclusion: Considering both direct and indirect costs, the cumulative costs of AS and immediate surgery in low-risk PTMC patients are similar during 10 years, and surgery could be more economical for patients with a life expectancy in long-term follow-up. However, careful interpretation is needed for long-term follow-up and the country's health care system and environment. Nevertheless, considering the representative protocols and objective costs in South Korea, it is expected to be a key to suggest the appropriate treatment for PTMC patients.

The Concept of Economic Evaluation and Its Application in Thyroid Cancer Research.

Economic evaluation is a type of comparative analysis between interventions in terms of both their resource use and health outcomes. Due to the good prognosis of thyroid cancer (TC), the socioeconomic burden of TC patients post-diagnosis is increasing. Therefore, economic evaluation studies focusing on TC are recommended. This study aimed to describe the concept and methods of economic evaluation and reviewed previous TC studies. Several previous studies compared the costs of interventions or evaluated recurrence, complications, or quality of life as measures of their effectiveness. Regarding costs, most studies focused on direct costs and applied hypothetical models. Cost-minimization analysis should be distinguished from simple cost analysis. Furthermore, due to the universality of the term "cost-effectiveness analysis" (CEA), several studies have not distinguished CEA from cost-utility analysis; this point needs to be considered in future research. Cost-benefit analyses have not been conducted in previous TC research. Since TC has a high survival rate and good prognosis, the need for economic evaluations has recently been pointed out. Therefore, correct concepts and methods are needed to obtain clear economic evaluation results. On this basis, it will be possible to provide appropriate guidelines for TC treatment and management in the future.