Secondhand smoke increases the risk of developing chronic obstructive pulmonary disease.

Smoking is the most important risk factor for chronic obstructive pulmonary disease (COPD), however evidence from large-scale studies on whether secondhand smoke (SHS) increases the risk of COPD is still lacking. We conducted this large longitudinal study to investigate the association between SHS and the development of COPD. This is a longitudinal study. Data on 6519 subjects who were never-smokers, had no history of COPD, and had complete lung function records were extracted from the Taiwan Biobank. They were divided into two groups according to SHS exposure: no exposure and exposure groups. Data were collected when participants enrolled in the study and during regular follow-up. Cox proportional hazards regression models were used to estimate the relative risk (RR) and 95% confidence interval (CI) for the association between SHS and the risk of developing COPD. At 48 months of follow-up, 260 (4%) participants in the no exposure group and 34 (7%) participants in the exposure group developed COPD. The RR of incident COPD development was significantly higher in the exposure group than that in the no exposure group after adjusting for confounders (RR = 1.49; 95% CI 1.04 to 2.14; P value = 0.031). There is a dose-response relationship between the duration of exposure to SHS and the risk of incident COPD, which demonstrates that an additional hour of exposure to SHS per week was associated with a 1.03-fold increased likelihood of developing COPD after adjusting for confounders (RR = 1.03; 95% CI 1.00 to 1.05; P value = 0.027). SHS exposure contributes to the development of COPD. This finding can help raise awareness of the harms of SHS and provide a reference for formulating anti-smoking policies.

The association of peritoneal dialysis and hemodialysis on mitral and aortic valve calcification associated mortality: a meta-analysis.

Cardiac valve calcification (CVC), characterized by the accumulation of calcium in the heart valves, is highly prevalent among patients undergoing dialysis. This meta-analysis aimed to provide an updated summary of recent studies on the prognostic value of CVC in patients undergoing dialysis. We conducted a search of PubMed, Embase, and Web of Science to identify observational studies investigating cardiovascular or all-cause mortality associated with CVC in dialysis patients until March 2023. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were calculated for the meta-analysis, and the strength and significance of the associations between CVC and mortality outcomes in dialysis patients were assessed. From 6218 initially identified studies, we included 10 critical studies with a total of 3376 dialysis patients in a further meta-analysis. Pooled analyses demonstrated a significant association between CVC and an elevated risk of all-cause and cardiovascular mortality in dialysis patients. In our study, we discovered HRs of 1.592 (95% CI 1.410-1.797) for all-cause mortality and 2.444 (95% CI 1.632-3.659) for cardiovascular mortality. Furthermore, subgroup analysis revealed elevated all-cause mortality among patients with mitral valve calcification (HR 1.572; 95% CI 1.200-2.060) compared to those with aortic valve calcification (HR 1.456; 95% CI 1.105-1.917). Similarly, patients undergoing peritoneal dialysis faced a greater risk for all-cause mortality (HR 2.094; 95% CI 1.374-3.191) than those on hemodialysis (HR 1.553; 95% CI 1.369-1.763). This highlights the possibility of CVC being an independent risk factor for dialysis patients, particularly in relation to mitral valve calcification or peritoneal dialysis.

The association between alcohol, betel nut, and cigarette use with hepatitis C virus infection in Taiwan.

Hepatitis C virus (HCV) infection may cause chronic liver disease, liver cirrhosis, and liver cancer. It has been reported to associate with habits including alcohol, betel nut and cigarette use. We aimed to investigate the association between alcohol, betel nut, and cigarette use with HCV infection in Taiwan and to explore their effects. A total of 121,421 participants were enrolled from the Taiwan Biobank. They were stratified into two groups according to whether they had (n = 2750; 2.3%) or did not have (n = 118,671; 97.7%) HCV infection. All participants were also classified into four groups according to the number of habits, including a history of alcohol drinking, betel nut chewing, and cigarette smoking. There were 85,406 (no habit), 24,299 (one habit), 8659 (two habits), and 3057 (three habits) participants in the four groups, respectively. Multivariable analysis showed that the participants who had an alcohol drinking history (odds ratio [OR] 1.568; 95% confidence interval [CI] 1.388-1.773; p < 0.001), betel nut chewing history (OR 1.664; 95% CI 1.445-1.917; p < 0.001), cigarette smoking history (OR 1.387; 95% CI 1.254-1.535; p < 0.001), were significantly associated with HCV infection. Furthermore, the participants were classified into four groups according to the number of habits as follows: 85,406 (no habit), 24,299 (one habit), 8659 (two habits), and 3057 (three habits). The HCV infection rates in these four groups were 2.11%, 2.14%, 3.23%, and 4.78%, respectively. Compared to the participants with no or one habit, those with two habits had a higher HCV infection rate (all p < 0.001). In addition, compared to the participants who had no, one or two habits, those who had three habits also had higher HCV infection rates (all p < 0.001). The participants who had three habits had the highest prevalence of HCV infection. In an era when most HCV can be cured, understanding the epidemiology link between habits and HCV may help the case finding.

Effect of far-infrared radiation therapy on von Willebrand factor in patients with chronic kidney disease.

Background: Hemostatic abnormality has contributed to vascular access thrombosis in patients with chronic kidney disease (CKD). Previous studies have demonstrated that far-infrared radiation (FIR) therapy can maintain the patency and maturity of arteriovenous fistulas of patients undergoing hemodialysis (HD). However, prolonged access bleeding is observed once FIR is conducted at the end of dialysis. FIR can block the binding of platelet and von Willebrand factor (vWF), a predictor of hemostatic abnormality and vascular access thrombosis. However, clinical studies exploring FIR and vWF are sparse. Methods: We recruited 20 HD patients, 21 CKD patients, and 20 controls to examine the alteration of vWF and a disintegrin and metalloproteinase with thrombospondin type 1 repeats 13 (ADAMTS13) following a single 40-min session of FIR therapy. In addition, the alteration of these factors in the HD group was examined following a 40-min FIR session thrice a week for 3 months. Results: A decreasing trend in the vWF activity-antigen ratio of participants in all groups following a single FIR session was observed. In addition, the ratio in the HD group was significantly lower following 3 months of FIR therapy. The subgroup analysis revealed a consistent trend and multiple regression analysis showed that participants not taking hydroxymethylglutaryl-coenzyme A reductase inhibitor, diabetes mellitus, and higher hemoglobin levels were the significant factors. The alteration of the vWF activity-antigen ratio correlated moderately to that of ADAMTS13 antigen and activity. Conclusion: FIR may alter the ratio of ultra-large vWF multimers through ADAMTS13, contributing to inhibiting platelet-endothelium interactions of CKD patients.

The impact of secondhand smoke on the development of kidney stone disease is not inferior to that of smoking: a longitudinal cohort study.

BACKGROUND: Tobacco use and secondhand smoke (SHS) are risk factors of kidney stone disease (KSD). The hypothesis is that tobacco produces chemicals that increase oxidative stress and vasopressin, which leads to decreased urine output, and contributes to stone formation. The aim of this study was to examine the effects of smoking and SHS on the development of KSD. MATERIALS AND METHODS: We analyzed a total of 25,256 volunteers with no history of KSD participated in the Taiwan Biobank. The presence of underlying and follow-up KSD was surveyed by a self-administrated questionnaire. They were classified into three groups on the basis of smoking and SHS exposure, accessed with survey questionnaires; never-smokers with no SHS exposure, never-smokers with SHS exposure and ever-smokers groups. RESULTS: KSD was noted in 352 (2.0%), 50 (3.3%) and 240 (4.1%) subjects in the never-smokers with no SHS exposure, never-smokers with SHS exposure and ever-smokers groups, respectively, with a mean follow-up of 4 years. The odds ratio (OR) of KSD was higher in the never-smokers with SHS exposure (OR, 1.622; 95% confidence interval [95% CI], 1.225 to 2.255) and ever-smokers groups (OR, 1.282; 95% CI, 1.044 to 1.574) than in the never-smokers with no SHS exposure group after adjustment of confounders. In addition, never-smokers with SHS exposure had similar effects on the development of KSD than ever-smokers (OR, 1.223; 95% CI, 0.852 to 1.756). CONCLUSION: Our study suggests that both smoking and SHS are a risk factor for developing KSD and that the impact of SHS is not inferior to that of smoking. TRIAL REGISTRATION: The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Kaohsiung Medical University Hospital (KMUHIRB-E(I)-20,210,058).

Arsenic exposure associated with lung interstitial changes in non-smoking individuals living near a petrochemical complex: A repeated cross-sectional study.

Arsenic exposure is associated with airway inflammation and decreased lung function tests. Whether arsenic exposure associated with lung interstitial changes remains unknown. We conducted this population-based study in southern Taiwan during 2016 and 2018. Our study recruited individuals aged over 20 years, residing in the vicinity of a petrochemical complex and with no history of cigarette smoking. In both the 2016 and 2018 cross-sectional studies, we conducted chest low-dose computed tomography (LDCT) scans, as well as urinary arsenic and blood biochemistry analyses. Lung interstitial changes included lung fibrotic changes that were defined as the presence of curvilinear or linear densities, fine lines, or plate opacity in specific lobes; additionally, other interstitial changes were defined as the presence of ground-glass opacity (GGO) or bronchiectasis on the LDCT images. In both cross-sectional studies conducted in 2016 and 2018, participants with lung fibrotic changes exhibited a statistically significant increase in the mean urinary arsenic concentrations compared to those without fibrotic changes (geometric mean = 100.1 vs. 82.8 µg/g creatinine, p < 0.001 for cross-sectional study 2016, and geometric mean = 105.6 vs. 71.0 µg/g creatinine, p < 0.001 for cross-sectional study 2018). After controlling for age, gender, body mass index, platelet counts, hypertension, aspartate aminotransferase, cholesterol, HbA1c, and educational levels, we observed a significant positive association between a unit increase in log urinary arsenic concentrations and the risk of lung fibrotic changes in both cross-sectional study 2016 (odds ratio [OR] = 1.40, 95% confidence interval [CI] = 1.04-1.90, p = 0.028) and cross-sectional study 2018 (OR = 3.03, 95% CI = 1.38-6.63, p = 0.006). Our study did not find a significant association between arsenic exposure and bronchiectasis or GGO. It is imperative for the government to take significant measures to reduce arsenic exposure levels among individuals living near petrochemical complexes.

Low Lung Function Is Associated with Low Baseline Calcaneus Ultrasound T-Score but a Slow Decline in T-Score in a Taiwanese Follow-Up Population with No History of Smoking, Bronchitis, Emphysema, or Asthma.

Osteoporosis is a common disease, and the prevalence is increasing in patients with chronic respiratory diseases, with important implications with regard to fractures, hospitalization, and death. Due to inconsistent data and a lack of large cohort follow-up studies on the association between lung function and osteoporosis, the aim of this study was to investigate this issue. We enrolled and followed for a median of 4 years a total of 9059 participants with no history of smoking, bronchitis, emphysema, or asthma from the Taiwan Biobank. Spirometry data, including forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), were used to assess lung function. Changes in the calcaneus ultrasound T-score (ΔT-score) were calculated as follow-up T-score-baseline T-score. A ΔT-score ≤ -3 (median value of ΔT-score) meant a fast decline in T-score. Multivariable analysis showed that lower values of FEV1 (ß, 0.127, p < 0.001), FVC (ß, 0.203, p < 0.001), and FEV1/FVC (ß, 0.002, p = 0.013) were significantly associated with a low baseline T-score. In addition, after follow-up, higher values of FEV1 (odds ratio (OR), 1.146, p = 0.001), FVC (OR, 1.110, p = 0.042), and FEV1/FVC (OR, 1.004, p = 0.002) were significantly associated with ΔT-score ≤ -3. FEV1/FVC < 70% (OR, 0.838, p < 0.001) was significantly associated with ΔT-score ≤ -3. In conclusion, lower FEV1, FVC, and FEV1/FVC were associated with a low baseline T-score, and higher FEV1, FVC, and FEV1/FVC were associated with a rapid decline in T-score in follow-up. This suggests that lung disease may be associated with bone mineral density in the Taiwanese population with no history of smoking, bronchitis, emphysema, or asthma. Further research is needed to establish causality.

Urinary copper levels are associated with bronchiectasis in non-smokers living near a petrochemical complex.

The incidence of respiratory diseases has been associated with copper in particulate matter; however, the relationship between urinary copper levels and interstitial lung changes remains unclear. Therefore, we conducted a population-based study in southern Taiwan between 2016 and 2018, excluding individuals with a history of lung carcinoma, pneumonia, and cigarette smoking. Low-dose computed tomography (LDCT) was performed to detect lung interstitial changes, including the presence of ground-glass opacity or bronchiectasis in LDCT images. We categorized urinary copper levels into quartiles (Q1: ≤10.3; Q2: >10.4 and ≤14.2; Q3: >14.3 and ≤18.9; and Q4: >19.0 µg/L) and analyzed the risk of interstitial lung changes using multiple logistic regression analysis. The urinary copper levels were significantly positively correlated with age, body mass index, serum white blood cell count, aspartate aminotransferase, alanine aminotransferase, creatinine, triglycerides, fasting glucose, and glycated hemoglobin and significantly negatively correlated with platelet count and high-density lipoprotein cholesterol. The study found that the highest quartile of urinary copper levels (Q4) was significantly associated with an increased risk of bronchiectasis compared to the lowest quartile (Q1) of urinary copper levels, with an odds ratio (OR) of 3.49 and a 95% confidence interval (CI) of 1.12-10.88. However, the association between urinary copper levels and interstitial lung disease needs further investigation in future studies.

Sex difference in the associations among risk factors with depression in a large Taiwanese population study.

Background: Depression is a common psychiatric health issue affecting an estimated 5% of adults worldwide, and it can lead to disability and increased economic burden. Consequently, identifying the factors associated with depression as early as possible is a vital issue. The aim of this study was to explore these associations in a large cohort of 121,601 Taiwanese participants in the Taiwan Biobank, and also to identify sex differences in the associations. Methods: The study cohort included 77,902 women and 43,699 men (mean age, 49.9 ± 11.0 years), who were further classified into those with depression (n = 4,362; 3.6%) and those without depression (n = 117,239; 96.4%). Results: The results of multivariable analysis showed that female sex (vs. male sex; odds ratio = 2.578; 95% confidence interval = 2.319-2.866; p < 0.001) was significantly associated with depression. Older age, diabetes mellitus (DM), hypertension, low systolic blood pressure (SBP), smoking history, living alone, low glycated hemoglobin (HbA1c), high triglycerides, and low uric acid were significantly associated with depression in the men. In the women, older age, DM, hypertension, low SBP, smoking history, alcohol history, education level of middle and high school (vs. lower than elementary school), living alone, high body mass index (BMI), menopause, low HbA1c, high triglycerides, high total cholesterol, low estimated glomerular filtration rate (eGFR), and low uric acid were significantly associated with depression. Further, there were significant interactions between sex and DM (p = 0.047), smoking history (p < 0.001), alcohol use (p < 0.001), BMI (p = 0.022), triglyceride (p = 0.033), eGFR (p = 0.001), and uric acid (p = 0.004) on depression. Conclusion: In conclusion, our results showed sex differences in depression, and the women were significantly associated with depression compared to men. Furthermore, we also found sex differences among the risk factors associated with depression.

The GLP-1 receptor agonist exenatide ameliorates neuroinflammation, locomotor activity, and anxiety-like behavior in mice with diet-induced obesity through the modulation of microglial M2 polarization and downregulation of SR-A4.

Obesity is associated with multiple comorbidities, such as metabolic abnormalities and cognitive dysfunction. Moreover, accumulating evidence indicates that neurodegenerative disorders are associated with chronic neuroinflammation. GLP-1 receptor agonists (RAs) have been extensively studied as a treatment for type 2 diabetes. Emerging evidence has demonstrated a protective effect of GLP-1 RAs on neurodegenerative disease, which is independent of its glucose-lowering effects. In this study, we aimed to examine the effects of a long-acting GLP-1 RA, exenatide, on high-fat diet (HFD)-induced neuroinflammation and related brain function impairment. First, mice treated with exenatide exhibited significantly reduced HFD-increased body weight and blood glucose. In an open field test, exenatide treatment ameliorated the reduction in local motor activity and anxiety in HFD-fed mice. Moreover, HFD induced astrogliosis, microgliosis, and upregulation of IL-1ß, IL-6 and TNF-α in hippocampus and cortex. Exenatide treatment reduced HFD-induced astrogliosis and IL-1ß and TNF-α expressions. Moreover, exenatide increased phosphor-ERK and M2-type microglia marker arginase-1 expression in the hippocampus and cortex. In addition, we found that scavenger receptor-A4 protein expression was induced by HFD and was subsequently inhibited by exenatide. SR-A4 knockout reversed the locomotor activity impairment but not the anxiety behavior caused by HFD consumption. SR-A4 knockout also reduced HFD-induced neuroinflammation, as shown by the reduced expression of GFAP and IBA-1 compared with that in wild-type control mice. These results demonstrate that exenatide decreases HFD-increased neuroinflammation and promotes anti-inflammatory M2 differentiation. The inhibition of SR-A4 by exenatide exerts anti-inflammatory activity.

KITLG Promotes Glomerular Endothelial Cell Injury in Diabetic Nephropathy by an Autocrine Effect.

Diabetic nephropathy (DN) is an increasing threat to human health. The impact of hyperglycemia or its metabolites, advanced glycation end-products (AGEs), on glomerular endothelial cells (GECs) and their pathophysiologic mechanisms are not well explored. Our results reveal that AGEs increased the expression and secretion of the KIT ligand (KITLG) in GECs. Both AGEs and KITLG promoted endothelial-to-mesenchymal transition (EndoMT) in GECs and further increased the permeability of GECs through the AKT/extracellular-signal-regulated kinase pathway. Inhibition of KITLG's effects by imatinib prevented AGE-medicated EndoMT in GECs, supporting the belief that KITLG is a critical factor for GEC injury. We found higher KITLG levels in the GECs and urine of db/db mice compared with db/m mice, and urinary KITLG levels were positively correlated with the urinary albumin-to-creatinine ratio (ACR). Furthermore, type 2 diabetic patients had higher urinary KITLG levels than normal individuals, as well as urinary KITLG levels that were positively correlated with urinary ACR and negatively correlated with the estimated glomerular filtration rate. KITLG plays a pathogenic role in GEC injury in DN and might act as a biomarker of DN progression.

Effects of Montelukast on Arsenic-Induced Epithelial-Mesenchymal Transition and the Role of Reactive Oxygen Species Production in Human Bronchial Epithelial Cells.

Background: Epithelial-mesenchymal transition (EMT) of airway lung epithelial cells is considered a major driver of fibrosis and airway remodeling. Arsenic exposure is well known to cause the malignant transformation of cells, including those in the lung. Accumulating studies have shown that arsenic exposure is associated with chronic pulmonary diseases. However, clinical treatment for arsenic-induced pulmonary damage has not been well investigated. Materials and Methods: The therapeutic effects of montelukast and its combination with fluticasone on sodium arsenite-induced EMT changes in normal human bronchial cells were investigated. The cell migration ability was evaluated by Transwell and wound healing assays. EMT marker expression was determined by immunoblotting. Furthermore, the role of reactive oxygen species (ROS) generation in arsenic-induced EMT and the effect of montelukast on this process were determined by ROS inhibitor treatment and ROS measurement, respectively. Results: Montelukast was effective at reducing arsenic-induced cell migration and mesenchymal protein (fibronectin, MMP-2, N-cadherin, ß-catenin, and SMAD2/3) expression. Arsenic-induced ROS production was attenuated by pretreatment with montelukast. Treatment with the ROS inhibitor N-acetyl cysteine reduced arsenic-induced NF-kB phosphorylation and the mesenchymal protein expression, indicating that ROS production is critical for arsenic-induced EMT. In addition, combined treatment with montelukast and fluticasone reversed the inhibitory effects of montelukast on cell migration. The expression of fibronectin, MMP-2 induced by arsenic was further enhanced by the combination treatment compared with montelukast treatment only. Conclusion: This study demonstrated that montelukast is effective at reducing arsenic-induced EMT in human bronchial epithelial cells. Through the inhibition of arsenic-induced ROS generation and NF-kB activation, which is critical for arsenic-induced EMT, montelukast inhibited arsenic-induced cell migration and the expression of extracellular matrix proteins and several EMT-regulating transcription factors. The combination of fluticasone with montelukast reversed the inhibitory effect of montelukast on arsenic-induced EMT. This study provides therapeutic strategies and mechanisms for arsenic-induced pulmonary epithelial damage.

Obesity-Related Indices Are Associated with Longitudinal Changes in Lung Function: A Large Taiwanese Population Follow-Up Study.

The global pandemic of obesity and the increasing incidence of chronic respiratory diseases are growing health concerns. The association between obesity and pulmonary function is uncertain. Therefore, this study aimed to explore associations between changes in lung function and obesity-related indices in a large longitudinal study. A total of 9059 participants with no personal histories of asthma, smoking, bronchitis, or emphysema were enrolled from the Taiwan Biobank and followed for 4 years. Lung function was assessed using spirometry measurements including forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). Changes in FEV1/FVC (∆FEV1/FVC) between baseline and follow-up were calculated. The following obesity-related indices were studied: lipid accumulation product (LAP), body roundness index (BRI), conicity index (CI), body adiposity index (BAI), abdominal volume index (AVI), body mass index (BMI), waist-hip ratio (WHR), and waist-to-height ratio (WHtR). In multivariable analysis, the subjects with high BMI (p < 0.001), WHR (p < 0.001), WHtR (p < 0.001), LAP (p = 0.002), BRI (p < 0.001), CI (p = 0.005), BAI (p < 0.001), and AVI (p < 0.001) were significantly associated with a high baseline FEV1/FVC. After 4 years of follow-up, the subjects with high BMI (p < 0.001), WHR (p < 0.001), WHtR (p < 0.001), LAP (p = 0.001), BRI (p < 0.001), CI (p = 0.002), BAI (p < 0.001), and AVI (p < 0.001) were significantly associated with a low △FEV1/FVC. High obesity-related index values were associated with better baseline lung function and a rapid decrease in lung function at follow-up.

Determinants of Longitudinal Change of Lung Function in Different Gender in a Large Taiwanese Population Follow-Up Study Categories: Original Investigation.

Chronic lung disease is associated with tremendous social and economic burden worldwide. The aim of this study was to investigate the sex-specific risk factors for changes in lung function in a large longitudinal study. We included 9059 participants from the Taiwan Biobank. None of the participants had a history of smoking, asthma, emphysema or bronchitis. Lung function was assessed using spirometry measurements of forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1). Change in the FEV1/FVC (ΔFEV1/FVC) was calculated as a follow-up FEV1/FVC minus baseline FEV1/FVC. Linear regression analysis was used to identify associations between variables and ΔFEV1/FVC in the male and female participants. After multivariable adjustments, the male participants (vs. females; p = 0.021) were significantly associated with a low ΔFEV1/FVC. In addition, the male participants with low aspartate aminotransferase (AST) (p = 0.003), high alanine aminotransferase (ALT) (p = 0.006) and a low estimated glomerular filtration rate (eGFR) (p = 0.003) were significantly associated with a low ΔFEV1/FVC. For the female participants, low systolic blood pressure (p = 0.005), low diastolic blood pressure (p = 0.031), low AST (p < 0.001), high ALT (p < 0.001) and a low eGFR (p = 0.001) were significantly associated with a low ΔFEV1/FVC. In this large follow-up study, we found that the male participants had a faster decrease in the FEV1/FVC than the female participants. In addition, liver and renal functions were correlated with changes in lung function in both the male and female participants. Our findings provide useful information on sex-specific changes in lung function.

Polypharmacy Is Significantly and Positively Associated with the Frailty Status Assessed Using the 5-Item FRAIL Scale, Cardiovascular Health Phenotypic Classification of Frailty Index, and Study of Osteoporotic Fractures Scale.

The aim of this study was to investigate the association between frailty and polypharmacy using three different frailty screening tools. This was a cross-sectional study of people aged ≥65 years. Participants were included and interviewed using questionnaires. Polypharmacy was defined as the daily use of eight or more pills. Frailty was assessed using a screening tool, including (1) the Fatigue, Resistance, Ambulation, Illness and Loss of Weight Index (5-item FRAIL scale), (2) the Cardiovascular Health Phenotypic Classification of Frailty (CHS_PCF) index (Fried's Frailty Phenotype), and (3) the Study of Osteoporotic Fracture (SOF) scale. A total of 205 participants (mean age: 71.1 years; 53.7% female) fulfilled our inclusion criteria. The proportion of patients with polypharmacy was 14.1%. After adjustments were made for comorbidity or potential confounders, polypharmacy was associated with frailty on the 5-item FRAIL scale (adjusted odds ratio [aOR]: 9.12; 95% confidence interval [CI]: 3.6-23.16), CHS_PCF index (aOR: 8.98; 95% CI: 2.51-32.11), and SOF scale (aOR: 6.10; 95% CI: 1.47-25.3). Polypharmacy was associated with frailty using three frailty screening tools. Future research is required to further enhance our understanding of the risk of frailty among older adults.

Secondhand smoke increases the risk of developing kidney stone disease.

Research indicates smoking increases the risk of various kidney diseases, although the risk of developing kidney stone disease in non-smokers exposed to secondhand smoke is unknown. This study analyzed a total of 19,430 never-smokers with no history of kidney stone disease who participated in the Taiwan Biobank from 2008 to 2019. They were divided into two groups by secondhand smoke exposure; no exposure and exposure groups; the mean age of participants was 51 years, and 81% were women. Incident kidney stone development was observed in 352 (2.0%) and 50 (3.3%) participants in the no exposure and exposure groups during a mean follow-up of 47 months. The odds ratio (OR) of incident kidney stone was significantly higher in the exposure group than the no exposure group [OR, 1.64; 95% confidence interval (95% CI) 1.21 to 2.23]. Participants with > 1.2 h per week exposure were associated with almost twofold risk of developing kidney stones compared with no exposure (OR, 1.92; 95% CI 1.29 to 2.86). Our study suggests that secondhand smoke is a risk factor for development of kidney stones and supports the need for a prospective evaluation of this finding.

The relationship of indoxyl sulfate and p-cresyl sulfate with target cardiovascular proteins in hemodialysis patients.

Protein-bound uremic toxins (Indoxyl sulfate [IS] and p-cresyl sulfate [PCS]) are both associated with cardiovascular (CV) and all-cause mortality in subjects with chronic kidney disease (CKD). Possible mechanisms have not been elucidated. In hemodialysis patients, we investigated the relationship between the free form of IS and PCS and 181 CV-related proteins. First, IS or PCS concentrations were checked, and high levels were associated with an increased risk of acute coronary syndrome (ACS) in 333 stable HD patients. CV proteins were further quantified by a proximity extension assay. We examined associations between the free form protein-bound uremic toxins and the quantified proteins with correction for multiple testing in the discovery process. In the second step, the independent association was evaluated by multivariable-adjusted models. We rank the CV proteins related to protein-bound uremic toxins by bootstrapped confidence intervals and ascending p-value. Six proteins (signaling lymphocytic activation molecule family member 5, complement component C1q receptor, C-C motif chemokine 15 [CCL15], bleomycin hydrolase, perlecan, and cluster of differentiation 166 antigen) were negatively associated with IS. Fibroblast growth factor 23 [FGF23] was the only CV protein positively associated with IS. Three proteins (complement component C1q receptor, CCL15, and interleukin-1 receptor-like 2) were negatively associated with PCS. Similar findings were obtained after adjusting for classical CV risk factors. However, only higher levels of FGF23 was related to increased risk of ACS. In conclusion, IS and PCS were associated with several CV-related proteins involved in endothelial barrier function, complement system, cell adhesion, phosphate homeostasis, and inflammation. Multiplex proteomics seems to be a promising way to discover novel pathophysiology of the uremic toxin.

Establishment of an outreach, grouping healthcare system to achieve microelimination of HCV for uremic patients in haemodialysis centres (ERASE-C).

OBJECTIVE: HCV prevails in uremic haemodialysis patients. The current study aimed to achieve HCV microelimination in haemodialysis centres through a comprehensive outreach programme. DESIGN: The ERASE-C Campaign is an outreach programme for the screening, diagnosis and group treatment of HCV encompassing 2323 uremic patients and 353 medical staff members from 18 haemodialysis centres. HCV-viremic subjects were linked to care for directly acting antiviral therapy or received on-site sofosbuvir/velpatasvir therapy. The objectives were HCV microelimination (>80% reduction of the HCV-viremic rate 24 weeks after the end of the campaign in centres with ≥90% of the HCV-viremic patients treated) and 'No-C HD' (no HCV-viremic subjects at the end of follow-up). RESULTS: At the preinterventional screening, 178 (7.7%) uremic patients and 2 (0.6%) staff members were HCV-viremic. Among them, 146 (83.9%) uremic patients received anti-HCV therapy (41 link-to-care; 105 on-site sofosbuvir/velpatasvir). The rates of sustained virological response (SVR12, undetectable HCV RNA 12 weeks after the end of treatment) in the full analysis set and per-protocol population were 89.5% (94/105) and 100% (86/86), respectively, in the on-site treatment group, which were comparable with the rates of 92.7% (38/41) and 100% (38/38), respectively, in the link-to-care group. Eventually, the HCV-viremic rate decreased to 0.9% (18/1,953), yielding an 88.3% reduction from baseline. HCV microelimination and 'No-C HD' were achieved in 92.3% (12/13) and 38.9% (7/18) of the haemodialysis centres, respectively. CONCLUSION: Outreach strategies with mass screenings and on-site group treatment greatly facilitated HCV microelimination in the haemodialysis population. CLINICALTRIALSGOV IDENTIFIER: NCT03803410 and NCT03891550.

Comedications and potential drug-drug interactions with direct-acting antivirals in hepatitis C patients on hemodialysis.

BACKGROUND/AIMS: Direct-acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. METHODS: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. RESULTS: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). CONCLUSION: HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

Association between Circulation Indole-3-Acetic Acid Levels and Stem Cell Factor in Maintenance Hemodialysis Patients: A Cross-Sectional Study.

: Protein-bound uremic toxin is a cardiovascular (CV) risk factor for patients with end-stage renal disease. Indole-3-acetic acid (IAA) was found to be associated with CV disease but the detailed pathophysiology remains unknown. Moreover, mitogen-activated protein kinase (MAPK) signaling cascades play an important role in the pathogenesis of CV disease. Thus, we explored the association between circulating IAA levels and forty MAPK cascade associated proteins in patients undergoing hemodialysis (HD). Circulating total form IAA was quantified by mass spectrometry and forty MAPK cascade associated proteins by a proximity extension assay in 331 prevalent HD patients. Accounting for multiple testing, and in multivariable-adjusted linear regression models, circulating total form IAA levels were positively associated with stem cell factor (ß coefficient 0.13, 95% confidence interval 0.04 to 0.21, p = 0.004). A bioinformatics approach using the search tool for interactions of chemicals (STITCH) tool provided information that IAA may be involved in the regulation of cell proliferation, hematopoietic cells, and the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. The knowledge gained here can be generalized, thereby impacting the non-traditional CV risk factors in patients with kidney disease. Further in vitro work is necessary to validate the translation of the mechanistic pathways.