Clinical characteristics and outcomes of patients with mpox during the 2022 mpox outbreak compared with those before the outbreak: A systematic review and meta-analysis.

On 23 July 2022, the World Health Organization declared the global mpox outbreak as a public health emergency of international significance. The mpox virus (MPXV) that caused the outbreak was classified as clade IIb, which belongs to the West African clade. However, the relationship between MPXV clades and symptoms, as well as the severity of mpox outcomes, is not fully understood. Thus, we aimed to investigate the global mpox prevalence and the differences in clinical manifestations and outcomes among patients with mpox between pre-outbreak (2003-2021) and the current mpox outbreak. In this systematic review and meta-analysis, PubMed/MEDLINE, Web of Science, Embase, Cumulative Index to Nursing and Allied Health Literature, and Google Scholar were searched using the keyword "monkeypox" and "mpox" up to 13 October 2022. A random effects model was used to obtain the pooled prevalence and 95% confidence intervals. This study included 27 articles, and 5698 patients with mpox with 19 distinctive features from 19 countries across five continents were assessed. Patients with mpox during the 2022 mpox outbreak showed mild clinical manifestations and outcomes compared with those before the 2022 mpox outbreak: mild rash (relative ratio [RR]: 5.09, 95% confidence interval [CI]: 1.52-17.08), fever (0.68, 0.49-0.94), pruritus (0.25, 0.19-0.32), myalgia (0.50, 0.31-0.81), headache (0.56, 0.35-0.88), skin ulcer (0.32, 0.17-0.59), abdominal symptom (0.29, 0.20-0.42), pharyngitis (0.32, 0.18-0.58), nausea or vomiting (0.15, 0.02-0.93), conjunctivitis (0.11, 0.03-0.38), concomitant infection with HIV (1.70, 0.95-3 0.04), and death (0.02, 0.001-0.31). MPXV clade IIb exhibited higher infectivity but may cause mild disease symptoms and low mortality rate. It is important to consider MPXV infection in patients with mpox-related features and/or a history of sexual transmission to prevent the spread of the disease and recognise the current pandemic threat.

Long-Term Autoimmune Inflammatory Rheumatic Outcomes of COVID-19 : A Binational Cohort Study.

BACKGROUND: Some data suggest a higher incidence of diagnosis of autoimmune inflammatory rheumatic diseases (AIRDs) among patients with a history of COVID-19 compared with uninfected patients. However, these studies had methodological shortcomings. OBJECTIVE: To investigate the effect of COVID-19 on long-term risk for incident AIRD over various follow-up periods. DESIGN: Binational, longitudinal, propensity-matched cohort study. SETTING: Nationwide claims-based databases in South Korea (K-COV-N cohort) and Japan (JMDC cohort). PARTICIPANTS: 10 027 506 Korean and 12 218 680 Japanese patients aged 20 years or older, including those with COVID-19 between 1 January 2020 and 31 December 2021, matched to patients with influenza infection and to uninfected control patients. MEASUREMENTS: The primary outcome was onset of AIRD (per appropriate codes from the International Classification of Diseases, 10th Revision) 1, 6, and 12 months after COVID-19 or influenza infection or the respective matched index date of uninfected control patients. RESULTS: Between 2020 and 2021, among the 10 027 506 Korean participants (mean age, 48.4 years [SD, 13.4]; 50.1% men), 394 274 (3.9%) and 98 596 (0.98%) had a history of COVID-19 or influenza, respectively. After propensity score matching, beyond the first 30 days after infection, patients with COVID-19 were at increased risk for incident AIRD compared with uninfected patients (adjusted hazard ratio, 1.25 [95% CI, 1.18 to 1.31]) and influenza-infected control patients (adjusted hazard ratio, 1.30 [CI, 1.02 to 1.59]). The risk for incident AIRD was higher with more severe acute COVID-19. Similar patterns were observed in the Japanese cohort. LIMITATIONS: Referral bias due to the pandemic; residual confounding. CONCLUSION: SARS-CoV-2 infection was associated with increased risk for incident AIRD compared with matched patients without SARS-CoV-2 infection or with influenza infection. The risk for incident AIRD was higher with greater severity of acute COVID-19. PRIMARY FUNDING SOURCE: National Research Foundation of Korea.

Risks of cutaneous immune-related adverse events in long COVID: Multinational cohort studies in South Korea, Japan, and the UK.

Previous research has not investigated the persistent cutaneous immune-related adverse events (cirAEs) related to long COVID to investigate the long-term sequelae. This multinational study, using a propensity-matched overlap weighting method, utilizes large national claims-based cohorts, using ICD-10 code diagnosis, focusing on patients aged ≥20 years from three countries: South Korean, Japanese, and the British cohorts. To estimate the risk of cirAEs in long COVID, the persistence or emergence of cirAEs occurring 4 weeks after the initial SARS-CoV-2 infection, we employed a Cox proportional hazard regression model. The Korean cohort (n = 5,937,373; mean age 49.2 years [SD: 13.2]), the Japanese cohort (n = 4,307,587; 42.5 years [13.6]), and the UK cohort (n = 395,435; 71.0 years [8.07]) were presented. An increased risk of cirAEs in long COVID was observed (HR, 1.10; 95% CI, 1.06-1.14) in Korean cohort, while a similar association was observed in Japanese and UK cohorts. The long-term risk of cirAEs in long COVID was higher in more severe COVID-19 cases (1.31; 1.22-1.39). Unlike the increased risk of cirAEs in long COVID, COVID-19 vaccination attenuated the risk, especially with two or more doses (1.03; 0.95-1.11) or heterologous regimens (0.98; 0.76-1.27). The time attenuation effect indicated a sustained risk for up to 6 months postinfection (<3 months: 1.13 [1.07-1.19]; 3-6 months: 1.14 [1.06-1.22]). SARS-CoV-2 infection is associated with an increased risk of cirAEs in the aspect of long COVID. Vaccination might reduce this risk, highlighting the need for preventive strategies in long COVID management.

National Trends in Allergic Rhinitis and Chronic Rhinosinusitis and COVID-19 Pandemic-Related Factors in South Korea, from 1998 to 2021.

INTRODUCTION: Existing studies provide insights into the prevalence and environmental factors associated with allergic rhinitis (AR) and chronic rhinosinusitis (CRS) globally. However, limitations still persist in these studies, particularly regarding cohort sizes and the duration of follow-up periods, indicating a need for more comprehensive and long-term research in these fields. Our study aimed to investigate the prevalence, long-term trends, and underlying factors of these conditions in the general population of adult participants (≥19 years) in Korea. METHOD: We analyzed data from adult participants (≥19 years) from the Korea National Health and Nutrition Examination Survey (KNHANES) study to determine the prevalence of AR and CRS from 1998 to 2021. To analyze prevalence trends before and during the COVID-19 pandemic, we employed a weighted linear regression model and obtained ß-coefficients with 95% confidence intervals (CI). RESULTS: Between 1998 and 2021, over a span of 24 years, the comprehensive KNHANES study included 146,264 adult participants (mean age: 47.80 years, standard deviation: 16.49 years; 66,177, 49.3% men). The prevalence of AR and CRS increased from 1998 to 2021, with AR prevalence rising from 5.84% (95% CI, 5.57-6.10) in 1998-2005 to 8.99% (8.09-9.91) in 2021 and CRS from 1.84% (1.70-1.97) in 1998-2005 to 3.70% (3.18-4.23) in 2021. However, the increasing trend has slowed down during the COVID-19 pandemic era. CONCLUSIONS: The significance of continuous monitoring and focused interventions for AR and CRS is underscored by this study. The observed deceleration in the rising prevalence of AR and CRS during the pandemic indicates the possibility of beneficial impacts from lifestyle modifications triggered by the pandemic. These findings call for additional research to explore potential protective effects in greater depth.

Association of Soda Drinks and Fast Food with Allergic Diseases in Korean Adolescents: A Nationwide Representative Study.

INTRODUCTION: A high consumption of carbonated soft drinks (i.e., soda drinks) and fast food is potentially associated with the observed global rise in adolescent allergic diseases. Thus, our study aimed to examine the potential associations between the consumption of soda drinks and fast food and allergic conditions, identifying specific relationships across subgroups and each allergic condition (asthma, allergic rhinitis, and atopic dermatitis). METHODS: This study uses large-scale data from the Korea Youth Risk Behavior Web-Based Survey (total n = 865,614). Soda drinks and fast food were defined by a self-reported questionnaire and allergic conditions by physician-diagnosed within 1 year. Multivariable logistic regression was used to analyze the weighted odds ratios (ORs), along with 95% confidence intervals (CIs), for allergic diseases associated with the intake of soda drinks and fast food. RESULTS: Among 865,614 adolescents in grades 7-12 (male, 51.40%), patients with asthma, allergic rhinitis, and atopic dermatitis were 18,568 (2.15%), 153,536 (17.74%), and 59,014 (6.82%), respectively. Current asthma was associated with soda drinks (OR, 1.07; 95% CI, 1.03-1.12) and fast food consumption (1.25; 1.17-1.33). Interestingly, stronger associations were observed for female high schoolers, compared to male high schoolers and middle schoolers, in relation to the consumption of soda drinks (1.31; 1.19-1.44) and fast food (1.46; 1.26-1.69) with asthma. Current allergic rhinitis and atopic dermatitis had no significant association with fast food consumption and soda drinks. CONCLUSION: This first large-scale study suggests that fast food and soda drinks consumption are potentially associated with current asthma, with stronger associations observed in females than males, underscoring the need for sex-specific allergy prevention programs.

Clinical manifestations of human Mpox infection: A systematic review and meta-analysis.

Little is known about the ongoing monkeypox (mpox) outbreak, and the clinical features of mpox in patients worldwide have not been rigorously analysed. Thus, we aimed to investigate the clinical features associated with mpox infection and understand the pathophysiology and characteristics of the disease. For this systematic review and meta-analysis, we searched PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and the Cochrane Database of Systematic Reviews for articles published till 16 September 2022. We used a random effects model to calculate the pooled prevalence and 95% confidence interval (CI). We used the I2 statistic to assess heterogeneity, Egger's test to assess publication bias, 95% prediction interval to determine the level of uncertainty, and the Newcastle-Ottawa Scale and Joanna Briggs Institute quality assessment tool to assess the risk of bias. Twenty-six relevant articles from 19 countries across 5 continents were included, and data on 5472 mpox patients with 18 unique features were analysed. The pooled prevalence of clinical features of mpox were rash (85.7%, 95% CI: 68.3-94.3; k = 21), chills (77.8%, 95% CI: 70.5-83.7; k = 3), and fever (62.3%, 95% CI: 51.3-71.6; k = 25), lymphadenopathy (58.6%, 95% CI: 47.2-69.2; k = 21), lethargy or exhaustion (46.8%, 95% CI: 30.7-63.5; k = 14), pruritus (40.6%, 95% CI: 28.5-54.0; k = 5), myalgia (36.0%, 95% CI: 24.3-49.7; k = 16), headache (34.6%, 95% CI: 23.4-47.8; k = 17), skin ulcer (31.1%, 95% CI: 18.6-47.1; k = 7), abdomen symptom (24.2%, 95% CI: 17.9-31.9; k = 11), pharyngitis (23.0%, 95% CI: 12.7-37.9; k = 14), respiratory symptom (19.5%, 95% CI: 6.8-44.6; k = 6), nausea or vomiting (13.0%, 95% CI: 4.6-31.9; k = 3), scrotal or penile oedema (10.7%, 95% CI: 6.3-17.7; k = 4), conjunctivitis (7.1%, 95% CI: 2.4-18.9; k = 6), and death (0.9%, 95% CI: 0.4-2.0; k = 26). This is the first international and comprehensive study to examine all clinical presentations of human mpox infection. Our systematic review proposes a comprehensive understanding of the current mpox outbreak and may serve as key data for future studies on the pathological mechanisms and epidemiology of mpox infections.

Gene-environment interaction in type 2 diabetes in Korean cohorts: Interaction of a type 2 diabetes polygenic risk score with triglyceride and cholesterol on fasting glucose levels.

Type 2 diabetes (T2D) is caused by genetic and environmental factors as well as gene-environment interactions. However, these interactions have not been systematically investigated. We analyzed these interactions for T2D and fasting glucose levels in three Korean cohorts, HEXA, KARE, and CAVAS, using the baseline data with a multiple regression model. Two polygenic risk scores for T2D (PRST2D ) and fasting glucose (PRSFG ) were calculated using 488 and 82 single nucleotide polymorphisms (SNP) for T2D and fasting glucose, respectively, which were extracted from large-scaled genome-wide association studies with multiethnic data. Both lifestyle risk factors and T2D-related biochemical measurements were assessed. The effect of interactions between PRST2D -triglyceride (TG) and PRST2D -total cholesterol (TC) on fasting glucose levels was observed as follows: ß ± SE = 0.0005 ± 0.0001, p = 1.06 × 10-19 in HEXA, ß ± SE = 0.0008 ± 0.0001, p = 2.08 × 10-8 in KARE for TG; ß ± SE = 0.0006 ± 0.0001, p = 2.00 × 10-6 in HEXA, ß ± SE = 0.0020 ± 0.0004, p = 2.11 × 10-6 in KARE, ß ± SE = 0.0007 ± 0.0004, p = 0.045 in CAVAS for TC. PRST2D -based classification of the participants into four groups showed that the fasting glucose levels in groups with higher PRST2D were more adversely affected by both the TG and TC. In conclusion, blood TG and TC levels may affect the fasting glucose level through interaction with T2D genetic factors, suggesting the importance of consideration of gene-environment interaction in the preventive medicine of T2D.

Global Incidence and Prevalence of Eosinophilic Esophagitis, 1976-2022: A Systematic Review and Meta-analysis.

BACKGROUND AND AIMS: Owing to 2018 expanded diagnostic criteria for eosinophilic esophagitis (EoE) and thus a possible increase in diagnosis, previous studies on the global incidence and prevalence of EoE may need to be updated. We aimed to describe global, regional, and national trends in the incidence and prevalence of EoE from 1976 to 2022 and analyze their associations with geographic, demographic, and social factors through a systematic review. METHODS: We searched the PubMed/MEDLINE, Embase, CINAHL, Google Scholar, and Cochrane databases from their inception dates to December 20, 2022, for studies that reported the incidence or prevalence of EoE in the general population. We calculated the global incidence and prevalence of EoE using pooled estimates with 95% confidence intervals (CIs) and performed subgroup analysis based on age, sex, race, geographical area, World Bank income group, and diagnostic criteria of EoE. RESULTS: Forty studies met the eligibility criteria, including over 288 million participants and 147,668 patients with EoE from 15 countries across the five continents. The global pooled incidence and prevalence of EoE were 5.31 cases per 100,000 inhabitant-years (95% CI, 3.98-6.63; number of studies, 27; sample population, 42,191,506) and 40.04 cases per 100,000 inhabitant-years (95% CI, 31.10-48.98; number of studies, 20; sample population, 30,467,177), respectively. The pooled incidence of EoE was higher in high-income countries (vs low- or middle-income countries), males, and North America (vs Europe and Asia). The global prevalence of EoE followed a similar pattern. The pooled prevalence of EoE gradually increased from 1976 to 2022 (1976-2001; 8.18; 95% CI, 3.67-12.69 vs 2017-2022; 74.42; 95% CI, 39.66-109.19 cases per 100,000 inhabitant-years). CONCLUSIONS: The incidence and prevalence of EoE have increased substantially and vary widely across the world. Further research is needed to evaluate the incidence and prevalence of EoE in Asia, South America, and Africa.

Comparison of clinical manifestations in mpox patients living with HIV versus without HIV: A systematic review and meta-analysis.

Currently, many cases of mpox patients living with the human immunodeficiency virus (HIV) have been reported. Immunocompromised mpox patients, including those living with HIV are noted for an increased risk for severe symptoms; however, existing studies did not focus on the statistical comparison of mpox outcomes associated with HIV. Thus, we conducted a systematic review and meta-analysis to evaluate and compare the clinical manifestations of mpox in people living with HIV (PLWH) and people without HIV. In this systematic review and meta-analysis, PubMed/MEDLINE, Embase, and Google Scholar were searched up to March 7, 2023. A random effects model was used to calculate the pooled prevalence along with the 95% confidence intervals (CI), and the odds ratio and its corresponding 95% CIs were calculated to elucidate the significance of each clinical feature for mpox patients with and without HIV. In this study, we included 99 published papers with 2413 patients with mpox (median age, 35.5 years; PLWH n = 1151) from 27 countries across six continents. The odds ratio of the mpox outcomes with PLWH in comparison to patients without HIV was found to be significant for skin rash (1.24, 95% CI: 1.01-1.53), proctitis (2.03, 95% CI: 1.36-3.04), cough (0.57, 95% CI: 0.33-0.98), and diarrhea (3.85, 95% CI: 1.24-11.98). The odds ratio of mpox patients with HIV for historical infections of syphilis was 2.14 (95% CI: 1.38-3.32), compared with those without HIV. This is the first international and comprehensive study that performed a systematic review and meta-analysis to statistically measure mpox manifestations according to HIV status. As clinical features related to mucosal contact were characteristically pronounced in PLWH, our systematic review provides insight that the primary invasion site of infection strongly relates to the outcomes of mpox.

National trends in physical activity among adolescents in South Korea before and during the COVID-19 pandemic, 2009-2021.

With the ongoing COVID-19 pandemic, several previous studies from different countries showed that physical activity (PA) decreased during the COVID-19 outbreak. However, few studies have examined the recent tendency of PA in the adolescent population. Thus, we aimed to investigate the long-term trend of PA in Korean youth and the prevalence changes between before and during the COVID-19 pandemic. Data from Korea Youth Risk Behavior Web-Based Survey (KYRBS) was collected for consecutive years between 2009 and 2021. The period was separated into prepandemic (2009-2019), early-pandemic (2020), and mid-pandemic (2021). Self-reported amount of PA was categorized into four groups (insufficient, aerobic, muscle strengthening, and both physical activities) according to World Health Organization (WHO) PA guidelines. A total of 840 488 adolescents aged 12-18 who fully responded to the survey were selected (response rate: 95.2%). The 13-year trends in the proportion of adolescents who reported aerobic and muscle-strengthening activities met or exceeded 2020 WHO exercise guidelines for adolescents plateaued (11.9% from 2009 to 2011, 14.2% from 2018 to 2019, 14.4% from 2020, and 14.0% from 2021); however, the slope decreased during the pandemic (ßdiff , -0.076; 95% confidence interval [CI], -0.123 to -0.029). Proportion of sufficient aerobic exercise among adolescents sharply decreased midst the pandemic (28.0% from 2009 to 2011, 29.4% from 2018 to 2019, and 23.8% from 2020; ßdiff , -0.266; 95% CI, -0.306 to -0.226) but increased again in 2021 (26.0% from mid-COVID 19; 95% CI, 25.4-26.7). Similar patterns were observed in Metabolic Equivalent Task (MET) score (MET-min/week; 804.1 from 2018 to 2019, 720.9 from 2020, and 779.6 from 2021). The mean difference in MET score between pre-COVID and post-COVID was -55.4 MET-min/week (95% CI, -70.5 to -40.3). Through a nationwide representative study, there was no significant difference with regard to the number of Korean adolescents who achieved the PA guidelines (pre and postpandemic); however, the prevalence of recommended levels of PA needs to increase more based on the trend before the COVID-19 outbreak. The findings of this study suggest reinforcement of the importance of public health policies for Korean youths to be more physically active, especially during and after the pandemic.

Privacy-Preserving Federated Model Predicting Bipolar Transition in Patients With Depression: Prediction Model Development Study.

BACKGROUND: Mood disorder has emerged as a serious concern for public health; in particular, bipolar disorder has a less favorable prognosis than depression. Although prompt recognition of depression conversion to bipolar disorder is needed, early prediction is challenging due to overlapping symptoms. Recently, there have been attempts to develop a prediction model by using federated learning. Federated learning in medical fields is a method for training multi-institutional machine learning models without patient-level data sharing. OBJECTIVE: This study aims to develop and validate a federated, differentially private multi-institutional bipolar transition prediction model. METHODS: This retrospective study enrolled patients diagnosed with the first depressive episode at 5 tertiary hospitals in South Korea. We developed models for predicting bipolar transition by using data from 17,631 patients in 4 institutions. Further, we used data from 4541 patients for external validation from 1 institution. We created standardized pipelines to extract large-scale clinical features from the 4 institutions without any code modification. Moreover, we performed feature selection in a federated environment for computational efficiency and applied differential privacy to gradient updates. Finally, we compared the federated and the 4 local models developed with each hospital's data on internal and external validation data sets. RESULTS: In the internal data set, 279 out of 17,631 patients showed bipolar disorder transition. In the external data set, 39 out of 4541 patients showed bipolar disorder transition. The average performance of the federated model in the internal test (area under the curve [AUC] 0.726) and external validation (AUC 0.719) data sets was higher than that of the other locally developed models (AUC 0.642-0.707 and AUC 0.642-0.699, respectively). In the federated model, classifications were driven by several predictors such as the Charlson index (low scores were associated with bipolar transition, which may be due to younger age), severe depression, anxiolytics, young age, and visiting months (the bipolar transition was associated with seasonality, especially during the spring and summer months). CONCLUSIONS: We developed and validated a differentially private federated model by using distributed multi-institutional psychiatric data with standardized pipelines in a real-world environment. The federated model performed better than models using local data only.

Impact of pitavastatin on new-onset diabetes mellitus compared to atorvastatin and rosuvastatin: a distributed network analysis of 10 real-world databases.

BACKGROUND: Statin treatment increases the risk of new-onset diabetes mellitus (NODM); however, data directly comparing the risk of NODM among individual statins is limited. We compared the risk of NODM between patients using pitavastatin and atorvastatin or rosuvastatin using reliable, large-scale data. METHODS: Data of electronic health records from ten hospitals converted to the Observational Medical Outcomes Partnership Common Data Model (n = 14,605,368 patients) were used to identify new users of pitavastatin, atorvastatin, or rosuvastatin (atorvastatin + rosuvastatin) for ≥ 180 days without a previous history of diabetes or HbA1c level ≥ 5.7%. We conducted a cohort study using Cox regression analysis to examine the hazard ratio (HR) of NODM after propensity score matching (PSM) and then performed an aggregate meta-analysis of the HR. RESULTS: After 1:2 PSM, 10,238 new pitavastatin users (15,998 person-years of follow-up) and 18,605 atorvastatin + rosuvastatin users (33,477 person-years of follow-up) were pooled from 10 databases. The meta-analysis of the HRs demonstrated that pitavastatin resulted in a significantly reduced risk of NODM than atorvastatin + rosuvastatin (HR 0.72; 95% CI 0.59-0.87). In sub-analysis, pitavastatin was associated with a lower risk of NODM than atorvastatin or rosuvastatin after 1:1 PSM (HR 0.69; CI 0.54-0.88 and HR 0.74; CI 0.55-0.99, respectively). A consistently low risk of NODM in pitavastatin users was observed when compared with low-to-moderate-intensity atorvastatin + rosuvastatin users (HR 0.78; CI 0.62-0.98). CONCLUSIONS: In this retrospective, multicenter active-comparator, new-user, cohort study, pitavastatin reduced the risk of NODM compared with atorvastatin or rosuvastatin.

Urinary chemokine C-X-C motif ligand 16 and endostatin as predictors of tubulointerstitial fibrosis in patients with advanced diabetic kidney disease.

BACKGROUND: Interstitial fibrosis and tubular atrophy (IFTA) is a well-recognized risk factor for poor renal outcome in patients with diabetic kidney disease (DKD). However, a noninvasive biomarker for IFTA is currently lacking. The purpose of this study was to identify urinary markers of IFTA and to determine their clinical relevance as predictors of renal prognosis. METHODS: Seventy patients with biopsy-proven isolated DKD were enrolled in this study. We measured multiple urinary inflammatory cytokines and chemokines by multiplex enzyme-linked immunosorbent assay in these patients and evaluated their association with various pathologic features and renal outcomes. RESULTS: Patients enrolled in this study exhibited advanced DKD at the time of renal biopsy, characterized by moderate to severe renal dysfunction [mean estimated glomerular filtration rate (eGFR) 36.1 mL/min/1.73 m2] and heavy proteinuria (mean urinary protein:creatinine ratio 7.8 g/g creatinine). Clinicopathologic analysis revealed that higher IFTA scores were associated with worse baseline eGFR (P < 0.001) and poor renal outcome (P = 0.002), whereas glomerular injury scores were not. Among measured urinary inflammatory markers, C-X-C motif ligand 16 (CXCL16) and endostatin showed strong correlations with IFTA scores (P = 0.001 and P < 0.001, respectively), and patients with higher levels of urinary CXCL16 and/or endostatin experienced significantly rapid renal progression compared with other patients (P < 0.001). Finally, increased urinary CXCL16 and endostatin were independent risk factors for poor renal outcome after multivariate adjustments (95% confidence interval 1.070-3.455, P = 0.029). CONCLUSIONS: Urinary CXCL16 and endostatin could reflect the degree of IFTA and serve as biomarkers of renal outcome in patients with advanced DKD.

Gene-environment interactions related to blood pressure traits in two community-based Korean cohorts.

Hypertension is a complex disorder caused by genetic and environmental risk factors. Recently, genome-wide association studies (GWASs) identified more than 100 genetic variants for blood pressure traits and hypertension. However, the interactions between these genetic variants and environmental factors have not been systematically investigated. Therefore, we examined the interaction between genetic and environmental risk factors in blood pressure traits using the genetic risk score (GRS). Two Korean community-based cohorts, Cohort I (KARE; N = 8,840) and Cohort II (CAVAS; N = 9,599), were used for this study, and GRSs were calculated from 42 GWAS single-nucleotide polymorphisms (SNPs) that were validated for their association in these cohorts. We calculated GRSs in both ways by considering the effect sizes of each SNP (weighted GRS) and not considering the effect sizes (unweighted GRS). The unweighted GRS was strongly associated with systolic blood pressure, diastolic blood pressure, and hypertension (p = 9.03 × 10 -47 , p = 9.41 × 10 -48 , and p = 3.22 × 10 -55 by meta-analysis, respectively) and the weighted GRS showed the similar results. The environmental factors of body mass index, waist circumference, and drinking status were significantly associated with blood pressure traits, and the interaction between these factors and GRSs were examined. However, no interactions were found with either the GRS or the individual SNPs considered for the GRS. Our findings show that it is challenging to find GRS-environment interactions regarding blood pressure traits.

Chronic kidney disease and undiagnosed atrial fibrillation in individuals with diabetes.

BACKGROUND: Diabetes is an independent risk factor for atrial fibrillation (AF), which is associated with increases in mortality and morbidity, as well as a diminished quality of life. Renal involvement in diabetes is common, and since chronic kidney disease (CKD) shares several of the same putative mechanisms as AF, it may contribute to its increased risk in individuals with diabetes. The objective of this study is to identify the relationship between CKD and the rates of newly-diagnosed AF in individuals with diabetes taking part in a screening program using a self-applied wearable electrocardiogram (ECG) patch. MATERIALS AND METHODS: The study included 608 individuals with a diagnosis of diabetes among 1738 total actively monitored participants in the prospective mHealth Screening to Prevent Strokes (mSToPS) trial. Participants, without a prior diagnosis of AF, wore an ECG patch for 2 weeks, twice, over a 4-months period and followed clinically through claims data for 1 year. Definitions of CKD included ICD-9 or ICD-10 chronic renal failure diagnostic codes, and the Health Profile Database algorithm. Individuals requiring dialysis were excluded from trial enrollment. RESULTS: Ninety-six (15.8%) of study participants with diabetes also had a diagnosis of CKD. Over 12 months of follow-up, 19 new cases of AF were detected among the 608 participants. AF was newly diagnosed in 7.3% of participants with CKD and 2.3% in those without (P < 0.05) over 12 months of follow-up. In a univariate Cox proportional hazard regression analysis, the risk of incident AF was 3 times higher in individuals with CKD relative to those without CKD: hazard ratios (HR) 3.106 (95% CI 1.2-7.9). After adjusting for the effect of age, sex, and hypertension, the risk of incident AF was still significantly higher in those with CKD: HR 2.886 (95% CI 1.1-7.5). CONCLUSION: Among individuals with diabetes, CKD significantly increases the risk of incident AF. Identification of AF prior to clinical symptoms through active ECG screening could help to improve the clinical outcomes in individuals with CKD and diabetes.

Optimal fasting plasma glucose and haemoglobin A1c levels for screening of prediabetes and diabetes according to 2-hour plasma glucose in a high-risk population: The Korean Diabetes Prevention Study.

BACKGROUND: The primary aim of this study was to assess the utility of fasting plasma glucose (FPG) and HbA1c to identify diabetes by the 2-hour plasma glucose (PG) criterion in the Korean population at high risk for diabetes. METHODS: A total of 1646 participants with a body mass index of ≥23 kg/m2 without having a history of diabetes were recruited in this study. The cut-off values of FPG and HbA1c for detecting diabetes were identified using the Youden index using receiver operating characteristic (ROC) analysis. The gold standard for diabetes prediction was defined by the 2-hour PG level of ≥200 mg/dL. RESULTS: The participants comprised 54.0% women, and the mean age of all participants was 55.0 ± 8.1 years. At baseline, FPG was 104.1 ± 14.2 mg/dL, the 2-hour PG value was 162.9 ± 55.3 mg/dL, and HbA1c was 5.9% ± 0.5%. Four hundred and forty-six subjects (27.1%) were diagnosed with diabetes and 976 subjects (59.3%) were determined to be at prediabetes. The area under the ROC curve (AUC) of FPG and HbA1c for diabetes were 0.776 and 0.802, while the AUC of FPG and HbA1c for prediabetes were 0.515 and 0.477. The optimal cut-off value for diagnosing diabetes of FPG and HbA1c were 104.5 mg/dL (sensitivity 75.8%, specificity 67.5%) and 5.9% (sensitivity 80.6%, specificity 63.8%), respectively. CONCLUSIONS: FPG of 104.5 mg/dL and HbA1c value of 5.9% (41 mmol/mol) can be used as an optimal screening value for diabetes by 2-hour PG criterion in the Korean population at high risk for diabetes.

Body mass index, diabetes, and the risk of Parkinson's disease.

BACKGROUND: There are conflicting findings in the literature regarding the association of body mass index and incidence of PD. OBJECTIVES: This study aimed to investigate the association of body mass index with the risk of PD incidence while considering diabetes mellitus as a major confounding factor. METHODS: We examined 6,800,601 individuals (aged ≥40 years) who were free of PD using the database of the Korean National Health Insurance Service. Cox proportional hazard regression was used to assess adjusted hazard ratios for PD with adjustment for potential confounders. Stratified analyses by diabetes status were also performed. RESULTS: A total of 33,443 individuals were diagnosed with PD during the follow-up period (7.3 years). An increased risk of PD incidence was observed in the underweight group versus the normal group (adjusted hazard ratio: 1.28; 95% confidence interval: 1.21-1.36), whereas a decreased risk of PD incidence was observed (adjusted hazard ratio: 0.88; 95% confidence interval: 0.88-0.93) in the obese group and (adjusted hazard ratio: 0.77; 95% confidence interval: 0.72-0.82) in the severely obese group. This association consistently persisted after stratification by diabetes mellitus status, with the steepest downward slope for PD risk present with increasing body mass index in patients with severe diabetes mellitus (i.e., long duration or complication). CONCLUSIONS: Being underweight and diabetes mellitus were associated with an increased risk of PD incidence, and effect of being underweight was more prominent in those with diabetes mellitus, with a dose-response relationship existing according to diabetes mellitus status. Further research is warranted to understand the clinical implications of the significant interaction between being underweight and diabetes mellitus status in the development of PD. © 2020 International Parkinson and Movement Disorder Society.

Catalpol protects against 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cytotoxicity in osteoblastic MC3T3-E1 cells.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a well-known environmental contaminant that produces a wide variety of adverse effects in humans. Catalpol, a major bioactive compound enriched in the dried root of Rehmannia glutinosa, is a major iridoid glycoside that alleviates bone loss. However, the detailed mechanisms underlying the effects of catalpol remain unclear. The present study evaluated the effects of catalpol on TCDD-induced cytotoxicity in osteoblastic MC3T3-E1 cells. Catalpol inhibited TCDD-induced reduction in cell viability and increases in apoptosis and autophagic activity in osteoblastic MC3T3-E1 cells. Additionally, pretreatment with catalpol significantly decreased the nitric oxide and nitrite levels compared with a control in TCDD-treated cells and significantly inhibited TCDD-induced increases in the levels of cytochrome P450 1A1 and extracellular signal-regulated kinase. Pretreatment with catalpol also effectively restored the expression of superoxide dismutase and extracellular signal-regulated kinase 1 and significantly enhanced the expression of glutathione peroxidase 4 and osteoblast differentiation markers, including alkaline phosphatase and osterix. Taken together, these findings demonstrate that catalpol has preventive effects against TCDD-induced damage in MC3T3-E1 osteoblastic cells.

Effect of Dipeptidyl Peptidase-4 Inhibitors on the Risk of Bone Fractures in a Korean Population.

BACKGROUND: There have been equivocal results in studies of the effects of dipeptidyl peptidase-4 inhibitors (DPP-4i) on fractures. In this study, we analyzed the effect of DPP-4i on bone fracture risk in a Korean population. METHODS: We extracted subjects (n = 11,164) aged 50 years or older from the National Health Insurance Service-National Sample Cohort 2.0 from 2009 to 2014. Our control group included subjects without diabetes (n = 5,582), and our treatment groups with diabetes included DPP-4i users (n = 1,410) and DPP-4i non-users (n = 4,172). The primary endpoint was the incidence of a composite outcome consisting of osteoporosis diagnosis, osteoporotic fractures, vertebral fractures, non-vertebral fractures, and femoral fractures. The secondary endpoint was the incidence of each individual component of the composite outcome. Survival analysis was performed with adjustment for age, gender, diabetes complications severity index, Charlson comorbidity index, hypertension medication, and dyslipidemia treatment. RESULTS: The incidence of the composite outcome per 1,000 person-years was 0.089 in DPP-4i users, 0.099 in DPP-4i non-users, and 0.095 in controls. There was no significant difference in fracture risk between DPP-4i users and DPP-4i non-users or controls after the adjustments (P > 0.05). The incidences of osteoporosis diagnosis, osteoporotic fractures, vertebral fractures, non-vertebral fractures, and femoral fractures were not significantly different between DPP-4i users and non-users. The results of subgroup analyses by gender and age were consistent. CONCLUSION: DPP-4i had no significant effect on the risk of fractures in a Korean population.

Tetrabromobisphenol A Promotes the Osteoclastogenesis of RAW264.7 Cells Induced by Receptor Activator of NF-kappa B Ligand In Vitro.

BACKGROUND: Tetrabromobisphenol A (TBBPA), one of the most widely used brominated flame-retardants, is a representative persistent organic pollutants group. Studies on TBBPA toxicity have been conducted using various target cells; however, few studies have investigated TBBPA toxicity in bone cells. Therefore, this study investigated the in vitro effects of TBBPA on osteoclasts, a cell type involved in bone metabolism. METHODS: RAW264.7 cells were cultured in medium containing 50 ng/mL receptor activator of nuclear factor kappa B ligand (RANKL) and varying concentrations of TBBPA. To evaluate the effects of TBBPA on the differentiation and function of osteoclasts, osteoclast-specific gene expression, tartrate-resistant acid phosphatase (TRAP) activity, bone resorbing activity, mitochondrial membrane potential (MMP) and mitochondrial superoxide were measured. RESULTS: The presence of 20 µ TBBPA significantly increased TRAP activity in RANKL-stimulated RAW264.7 cells, the bone resorbing activity of osteoclasts, and the gene expression of Akt2, nuclear factor of activated T-cells cytoplasmic 1, and chloride channel voltage-sensitive 7. However, TBBPA treatment caused no change in the expression of carbonic anhydrase II, cathepsin K, osteopetrosis-associated transmembrane protein 1, Src, extracellular signal-related kinase, GAB2, c-Fos, or matrix metalloproteinase 9. Furthermore, 20 µ TBBPA caused a significant decrease in MMP and a significant increase in mitochondrial superoxide production. CONCLUSION: This study suggests that TBBPA promotes osteoclast differentiation and activity. The mechanism of TBBPA-stimulated osteoclastogenesis might include increased expression of several genes involved in osteoclast differentiation and reactive oxygen species production.