Prevalence and risk factors of non-tuberculous mycobacterial pulmonary isolates and infection in interstitial lung disease associated with systemic autoimmune disease.

OBJECTIVES: Non-tuberculous mycobacterial (NTM) lung disease (NTM-LD) prevalence is increasing worldwide. In this study, we aimed to evaluate the clinical significance of NTM pulmonary isolates (NTM-PI) and NTM-LD in patients with systemic autoimmune disease (SAD) who had a concurrent interstitial lung disease (ILD) diagnosis. METHODS: We retrospectively identified patients with SAD who had a concurrent ILD diagnosis (SAD-ILD) and from whom clinically indicated sputum specimens were collected for NTM culture between 2003 and 2018 at a tertiary referral hospital. We analysed the prevalence and risk factors of NTM pulmonary isolates (NTM-PI; ≥1 positive culture) and NTM-LD (≥2 positive cultures). RESULTS: This study included 258 patients. Rheumatoid arthritis and Sjögren's syndrome were the most common SADs (32.2% and 26.7%, respectively). The NTM-negative subgroup had 204 patients (79.1%) and the NTM-PI subgroup had 54 patients (20.9%). In the NTM-PI subgroup, 33 patients had one NTM positive set of specimens (NTM 1+, 12.8% of the entire sample) and 21 had NTM-LD (8.1% of the entire sample). In a multivariable analysis, chronic kidney disease (CKD; adjusted odds ratio [aOR]: 3.10 [1.53, 6.29]) and chronic obstructive pulmonary disease (COPD; aOR: 2.59 [1.16, 5.78]) were significantly associated with NTM-PI. For NTM-LD, CKD (aOR: 2.79 [1.00, 7.76]) and COPD (aOR: 3.70 [1.23, 10.72]) remained significant risk factors. CONCLUSIONS: In patients with SAD-ILD, the NTM-PI and NTM-LD prevalence rates were 20.9% and 8.1%, respectively. COPD and CKD were independent risk factors of both NTM-PI and NTM-LD. Previous use of biological agents was associated with NTM-PI.

The largest genome-wide association study for breast cancer in Taiwanese Han population.

PURPOSE: Breast cancer is a molecularly heterogeneous disease, and multiple genetic variants contribute to its development and prognosis. Most of previous genome-wide association studies (GWASs) and polygenic risk scores (PRSs) analyses focused on studying breast cancers of Caucasian populations, which may not be applicable to other population. Therefore, we conducted the largest breast cancer cohort of Taiwanese population to fill in the knowledge gap. METHODS: A total of 152,534 Participants recruited by China Medical University Hospital between 2003 and 2019 were filtered by several patient selection criteria and GWAS quality control steps, resulting in the inclusion of 2496 cases and 9984 controls for this study. We then conducted GWAS for all breast cancers and PRS analyses for all breast cancers and the four breast cancer subtypes, including luminal A, luminal B, basal-like, and HER2-enriched. RESULTS: The GWAS analyses identified 113 SNPs, 50 of which were novel. The PRS models for all breast cancers and the luminal A subtype showed positively correlated trends between the PRS and the risk of developing breast cancer. The odds ratios (95% confidence intervals) for the groups with the highest PRS in all breast cancers and the luminal A subtype were 5.33 (3.79-7.66) and 3.55 (2.13-6.14), respectively. CONCLUSION: In summary, we explored the association of genetic variants with breast cancer in the largest Taiwanese cohort and developed two PRS models that can predict the risk of developing any breast cancer and the luminal A subtype in Taiwanese women.

Risk factors for 5-year complications after midurethral sling surgery for stress urinary incontinence: a retrospective cohort study from Taiwan.

Midurethral sling surgery is the current gold standard worldwide for stress urinary incontinence (SUI) surgery, with over 90% of surgeons worldwide using the midurethral sling for SUI between 2008 and 2018. However, concerns surround mesh-related adverse events associated with the midurethral sling. The decision to use the midurethral sling for surgical treatment has become a challenging one for clinicians, surgeons and patients. We sought to determine the factors for 5-year complications after midurethral sling surgery, to improve the clinical decision-making process. Records were reviewed from a total of 1961 female patients who underwent their first midurethral sling surgery for SUI between 2003 and 2018 at a single teaching hospital in Taiwan. A multivariable Cox proportional hazard model calculated the hazard ratios of risk factors for surgical complications, after adjusting for confounders. Surgical complications (i.e., secondary surgery and urinary retention) occurred in 93 (4.7%) patients within 5 years following the index operations. These patients were more likely to be older, to have a history of menopausal syndrome within 1 year prior to the index operation, a medication history of oral antidiabetic drug use, hormone replacement therapy (HRT), slower average flow rate, and longer voiding time compared with patients without surgical complications. In the multivariate analysis, HRT (adjusted hazard ratio, 1.787; 95% confidence interval, 1.011-3.158, p = 0.04) was significantly associated with surgical complications at 5 years, after adjusting for age, gender, diabetes, menopause syndrome, average flow rate, and sling type. Our findings suggest that a medication history of HRT may be a risk factor associated with surgical complications, especially urinary retention, at 5 years in women undergoing midurethral sling surgery for SUI.

Age-specific percentile-based prostate-specific antigen cutoff values predict the risk of prostate cancer: A single hospital observation.

Background: Testing for prostate-specific antigen (PSA) is often recommended for men with a potential risk of prostate cancer (PCa) before requiring advanced examination. However, the best PSA cutoff value remains controversial. Object: We compared the predictive performance of age-specific percentile-based PSA thresholds with a conventional cutoff of >4 ng/mL for the risk of PCa. Methods: We included men who received PSA measurements between 2003 and 2017 in a medical center in Taiwan. Logistic regression modeling was used to assess the association between age-specific percentile-based PSA thresholds and PCa risk in age subgroups. We further applied C-statistic and decision curve analysis to compare the predictive performance of age-specific percentile-based PSA with that of a conventional cutoff PSA. Results: We identified 626 patients with PCa and 40 836 patients without PCa. The slope of PSA in patients >60-year-old was almost 3 times that of those <60-year-old (0.713 vs 0.259). The risk effect sizes of the 75th percentile PSA cutoff (<60-year-old: 2.19; 60-70-year-old: 4.36; >70-year-old: 5.84 ng/mL) were comparable to those observed based on the conventional cutoff in all age groups. However, the discrimination performance of the 75th percentile PSA cutoff was better than that of the conventional cutoff among patients aged <60-year-old (C-statistic, 0.783 vs. 0.729, p < 0.05). The 75th percentile cutoffs also correctly identified an additional 2 patients with PCa for every 100 patients with PSA screening at the threshold probability of 20%. Conclusions: Our data support the use of the 75th percentile PSA cutoff to facilitate individualized risk assessment, particularly for patients aged <60-year-old.

Validation of Gait Measurements on Short-Distance Walkways Using Azure Kinect DK in Patients Receiving Chronic Hemodialysis.

Muscle dysfunction, skeletal muscle fibrosis, and disability are associated with weakness in patients with end-stage renal disease. The main purpose of this study was to validate the effectiveness of a proposed system for gait monitoring on short-distance 1.5 m walkways in a dialysis center. Gaits with reduced speed and stride length, long sit-to-stand time (SST), two forward angles, and two unbalanced gait regions are defined in the proposed Kinect v3 gait measurement and analysis system (K3S) and have been considered clinical features in end-stage renal disease (ESRD) associated with poor dialysis outcomes. The stride and pace calibrations of the Kinect v3 system are based on the Zeno Walkway. Its single rating intraclass correlation (ICC) for the stride is 0.990, and its single rating ICC for the pace is 0.920. The SST calibration of Kinect v3 is based on a pressure insole; its single rating ICC for the SST is 0.871. A total of 75 patients on chronic dialysis underwent gait measurement and analysis during walking and weighing actions. After dialysis, patients demonstrated a smaller stride (p < 0.001) and longer SST (p < 0.001). The results demonstrate that patients' physical fitness was greatly reduced after dialysis. This study ensures patients' adequate physical gait strength to cope with the dialysis-associated physical exhaustion risk by tracing gait outliers. As decreased stride and pace are associated with an increased risk of falls, further studies are warranted to evaluate the clinical benefits of monitoring gait with the proposed reliable and valid system in order to reduce fall risk in hemodialysis patients.

Cardiothoracic ratio values and trajectories are associated with risk of requiring dialysis and mortality in chronic kidney disease.

BACKGROUND: The prognostic role of the cardiothoracic ratio (CTR) in chronic kidney disease (CKD) remains undetermined. METHODS: We conducted a retrospective cohort study of 3117 patients with CKD aged 18-89 years who participated in an Advanced CKD Care Program in Taiwan between 2003 and 2017 with a median follow up of 1.3(0.7-2.5) and 3.3(1.8-5.3) (IQR) years for outcome of end-stage renal disease (ESRD) and overall death, respectively. We developed a machine learning (ML)-based algorithm to calculate the baseline and serial CTRs, which were then used to classify patients into trajectory groups based on latent class mixed modelling. Association and discrimination were evaluated using multivariable Cox proportional hazards regression analyses and C-statistics, respectively. RESULTS: The median (interquartile range) age of 3117 patients is 69.5 (59.2-77.4) years. We create 3 CTR trajectory groups (low [30.1%], medium [48.1%], and high [21.8%]) for the 2474 patients with at least 2 CTR measurements. The adjusted hazard ratios for ESRD, cardiovascular mortality, and all-cause mortality in patients with baseline CTRs ≥0.57 (vs CTRs <0.47) are 1.35 (95% confidence interval, 1.06-1.72), 2.89 (1.78-4.71), and 1.50 (1.22-1.83), respectively. Similarly, greater effect sizes, particularly for cardiovascular mortality, are observed for high (vs low) CTR trajectories. Compared with a reference model, one with CTR as a continuous variable yields significantly higher C-statistics of 0.719 (vs 0.698, P = 0.04) for cardiovascular mortality and 0.697 (vs 0.693, P < 0.001) for all-cause mortality. CONCLUSIONS: Our findings support the real-world prognostic value of the CTR, as calculated by a ML annotation tool, in CKD. Our research presents a methodological foundation for using machine learning to improve cardioprotection among patients with CKD.

An enlarged heart occurs during various medical conditions and can result in early death. However, it is unclear whether this is also the case in patients with chronic kidney disease (CKD). Although the size of the heart can be measured on chest X-rays, this process is time consuming. We used artificial intelligence to quantify the heart size of 3117 CKD patients based on their chest X-rays within hours. We found that CKD patients with an enlarged heart were more likely to develop end-stage kidney disease or die. This could improve monitoring of CKD patients with an enlarged heart and improve their care.

Association between coronary artery calcium and all-cause mortality: A large single-center retrospective cohort study.

OBJECTIVE: Previous studies have revealed that coronary artery calcium is related to cardiovascular diseases and mortality. However, most studies have been conducted in Western countries and have excluded patients with pre-existing heart disease. We investigated the association between coronary artery calcium (CAC) and all-cause mortality in an Asian cohort and in subgroups stratified by age, sex, smoking, obesity, diabetes, cardiovascular disease, blood pressure, and biochemical parameters. METHODS: We conducted a retrospective cohort study on 4529 health examinees who underwent multidetector computed tomography in a tertiary medical center in Taiwan between 2011 and 2016. The mean follow-up was 3.5 years. Cox regression was used to estimate the relative hazards of death. Stratified analyses were performed. RESULTS: The all-cause mortality rates were 2.94, 4.88, 17.6, and 33.1 per 1000 person-years for CAC scores of 0, 1-100, 101-400, and >400, respectively. The multivariable adjusted hazard ratios (95% confidence intervals [CIs]) for all-cause mortality were 0.95 (0.53, 1.72), 1.87 (0.89, 3.90), and 3.05 (1.46, 6.39) for CAC scores of 1-100, 101-400, and >400, respectively, relative to a CAC score of 0. Compared with CAC ≤ 400, the HRs (95% CIs) for CAC > 400 were 6.46 (2.44, 17.15) and 1.94 (1.00, 3.76) in younger and older adults, respectively, indicating that age was a moderating variable (p = 0.02). CONCLUSION: High CAC scores were associated with increased all-cause mortality. Although older adult patients had higher risks of death, the relative risk of death for patients with CAC > 400 was more prominent in people younger than 65 years.

Association of poorly controlled HbA1c with increased risk of progression to end-stage kidney disease and all-cause mortality in patients with diabetes and chronic kidney disease.

Glycosylated hemoglobin (HbA1c) targets for patients with chronic kidney disease (CKD) and type 2 diabetes remain controversial. To evaluate whether baseline HbA1c and HbA1c trajectories are associated with the risk of end-stage kidney disease (ESKD) and all-cause mortality, we recruited adult patients with CKD and type 2 diabetes from a "Pre-ESKD Program" at a medical center in Taiwan from 2003 to 2017. Group-based trajectory modeling was performed to identify distinct patient groups that contained patients with similar longitudinal HbA1c patterns. Cox proportional hazard models were used to estimate hazard ratios (HRs) of ESKD and mortality associated with baseline HbA1c levels and HbA1c trajectories. In the analysis related to baseline HbA1c (n = 4543), the adjusted HRs [95% confidence interval (CI)] of all-cause mortality were 1.06 (0.95-1.18) and 1.25 (95% CI, 1.07-1.46) in patients with an HbA1c level of 7%-9% (53-75 mmol/mol) and >9% (>75 mmol/mol), respectively, as compared with those with an HbA1c level < 7% (<53 mmol/mol). In the trajectory analysis (n = 2692), three distinct longitudinal HbA1c trajectories were identified: nearly optimal (55.9%), moderate to stable (34.2%), and poor control (9.9%). Compared with the "nearly optimal" HbA1c trajectory group, the "moderate-to-stable" group did not have significantly higher mortality, but the "poorly controlled" group had 35% higher risk of mortality (adjusted HR = 1.35, 95% CI = 1.06-1.71). Neither baseline levels of HbA1c nor trajectories were associated with ESKD risk. In conclusion, in patients with CKD and type 2 diabetes, poor glycemic control was associated with an elevated risk of mortality but not associated with a risk of progression to ESKD.

Application of machine learning methods for the prediction of true fasting status in patients performing blood tests.

The fasting blood glucose (FBG) values extracted from electronic medical records (EMR) are assumed valid in existing research, which may cause diagnostic bias due to misclassification of fasting status. We proposed a machine learning (ML) algorithm to predict the fasting status of blood samples. This cross-sectional study was conducted using the EMR of a medical center from 2003 to 2018 and a total of 2,196,833 ontological FBGs from the outpatient service were enrolled. The theoretical true fasting status are identified by comparing the values of ontological FBG with average glucose levels derived from concomitant tested HbA1c based on multi-criteria. In addition to multiple logistic regression, we extracted 67 features to predict the fasting status by eXtreme Gradient Boosting (XGBoost). The discrimination and calibration of the prediction models were also assessed. Real-world performance was gauged by the prevalence of ineffective glucose measurement (IGM). Of the 784,340 ontologically labeled fasting samples, 77.1% were considered theoretical FBGs. The median (IQR) glucose and HbA1c level of ontological and theoretical fasting samples in patients without diabetes mellitus (DM) were 94.0 (87.0, 102.0) mg/dL and 5.6 (5.4, 5.9)%, and 92.0 (86.0, 99.0) mg/dL and 5.6 (5.4, 5.9)%, respectively. The XGBoost showed comparable calibration and AUROC of 0.887 than that of 0.868 in multiple logistic regression in the parsimonious approach and identified important predictors of glucose level, home-to-hospital distance, age, and concomitantly serum creatinine and lipid testing. The prevalence of IGM dropped from 27.8% based on ontological FBGs to 0.48% by using algorithm-verified FBGs. The proposed ML algorithm or multiple logistic regression model aids in verification of the fasting status.

Dyslipidemia and coronary artery calcium: From association to development of a risk-prediction nomogram.

BACKGROUND AND AIMS: The associations between dyslipidemia and coronary artery calcium (CAC) are controversial. We investigated their cross-sectional relationships and developed a predictive scoring system for prognostically significant coronary calcification (PSCC). METHODS AND RESULTS: This study evaluated the lipid profiles and the CAC score (CACS) measured through multidetector computed tomography (MDCT) among Taiwanese adult patients in a tertiary hospital between 2011 and 2016. Patients with CACS higher than 100 were classified as having PSCC. Dyslipidemia for each lipid component was defined based on the clinical cutoffs or the use of the lipid-lowering agents. Multivariable logistic regression was used to assess the association between dyslipidemia and PSCC and the model performance was assessed using calibration plot, discrimination, and a decision curve analysis. Of the 3586 eligible patients, 364 (10.2%) had PSCC. Increased age, male sex, higher body mass index (BMI), and higher level of triglyceride (TG) were associated with PSCC. The adjusted odds ratios (95% confidence intervals) of PSCC was 1.15 (0.90-1.47) for dyslipidemia defined by total cholesterol (TC) ≥200 mg/dL, 1.06 (0.83-1.35) for low-density-lipoprotein-cholesterol (LDL-C) ≥130 mg/dL, and 1.36 (1.06-1.75) for TG ≥ 200 mg/dL. The positive association between TG ≥ 200 mg/dL and PSCC was not modified by sex. Incorporating hypertriglyceridemia did not significantly improve the predictive performance of the base model comprising of age, sex, BMI, smoking, hypertension, diabetes, estimated glomerular filtration rate, and fasting glucose. CONCLUSIONS: Hypertriglyceridemia was significantly associated with the prevalent odds of PSCC. Our proposed predictive model may be a useful screening tool for PSCC.

Association of water intake and hydration status with risk of kidney stone formation based on NHANES 2009-2012 cycles.

OBJECTIVE: Evaluating the association of water intake and hydration status with nephrolithiasis risk at the population level. DESIGN: It is a cross-sectional study in which daily total plain water intake and total fluid intake were estimated together with blood osmolality, urine creatinine, urine osmolality, urine flow rate (UFR), free water clearance (FWC) and urine/blood osmolality ratio (Uosm:Bosm). The associations of fluid intake and hydration markers with nephrolithiasis were evaluated using multivariable logistic regression. SETTING: General US population. PARTICIPANTS: A total of 8195 adults aged 20 years or older from the National Health and Nutritional Examination Survey 2009-2012 cycles. RESULTS: The population medians (interquartile ranges, IQR) for daily total plain water intake and total fluid intake were 807 (336-1481) and 2761 (2107-3577) ml/d, respectively. The adjusted OR (95 % CI) of nephrolithiasis for each IQR increase in total plain water intake and total fluid intake were 0·92 (95 % CI 0·79, 1·06) and 0·84 (95 % CI 0·72, 0·97), respectively. The corresponding OR of nephrolithiasis for UFR, blood osmolality, Uosm:Bosm and urine creatinine were 0·87 (95 % CI 0·76, 0·99), 1·18 (95 % CI 1·06, 1·32), 1·38 (95 % CI 1·17, 1·63) and 1·27 (95 % CI 1·11, 1·45), respectively. A linear protective relationship of fluid intake, UFR and FWC with nephrolithiasis risk was observed. Similarly, positive dose-response associations of nephrolithiasis risk with markers of insufficient hydration were identified. Encouraging a daily water intake of >2500 ml/d and maintaining a urine output of 2 l/d was associated with a lower prevalence of nephrolithiasis. CONCLUSION: This study verified the beneficial role of general water intake recommendations in nephrolithiasis prevention in the general US population.

Insomnia and Poor Sleep in CKD: A Systematic Review and Meta-analysis.

Rationale & Objective: Poor sleep quality and insomnia are pervasive among patients with advanced chronic kidney disease (CKD); however, these health issues have not been systematically evaluated. Study Design: Systematic review and meta-analysis. Setting & Study Populations: Adult patients with CKD not receiving kidney replacement therapy (KRT), as well as adults receiving KRT, including hemodialysis, peritoneal dialysis, and kidney transplantation. Selection Criteria for Studies: A systematic literature search using PubMed, Embase, and PsycNET, was conducted for articles published between January 1, 1990, and September 28, 2018. Data Extraction: Data on the prevalences of poor sleep quality and insomnia in patients with CKD, including those receiving and not receiving KRT, were extracted. Analytical Approach: Pooled prevalences were estimated using a random-effects meta-analysis and were stratified according to age, CKD stage, World Health Organization region, risk of bias, Pittsburgh Sleep Quality Index score, and the different criteria for insomnia that were used at diagnosis. Results: Of 3,708 articles, 93 were selected, and significant methodological heterogeneity was present. The pooled prevalences of poor sleep quality for CKD without KRT, hemodialysis, peritoneal dialysis, and kidney transplantation were 59% (95% CI, 44%-73%), 68% (95% CI, 64%-73%), 67% (95% CI, 44%-86%), and 46% (95% CI, 34%-59%), respectively. The corresponding prevalences of insomnia were 48% (95% CI, 30%-67%), 46% (95% CI, 39%-54%), 61% (95% CI, 41%-79%), and 26% (95% CI, 9%-49%), respectively. Insomnia was significantly more prevalent among patients aged 51-60 years and those aged >60 years than among those aged <50 years. The prevalence of insomnia in the European region was the lowest of all World Health Organization regions. Limitations: High interstudy heterogeneity. Conclusions: Approximately half of the patients with advanced CKD had poor sleep quality or insomnia, and the prevalence was even higher among those who received KRT. Kidney transplantation may reduce the burden of poor sleep quality and insomnia.

Comparison of pharmaco-mechanical thrombolysis and catheter-directed thrombolysis for treating thrombotic or embolic arterial occlusion of the lower limb.

BACKGROUND: Whether pharmaco-mechanical thrombolysis (PMT) results in superior outcomes to catheter-directed thrombolysis (CDT) in treating thrombotic or embolic arterial occlusion of the lower limbs is unclear. METHODS: We enrolled 94 patients with Rutherford class I-IIb due to thrombotic or embolic arterial occlusion in the lower limbs and who received emergency endovascular treatment. Baseline demographics, laboratory data, angiography and clinical outcomes were collected through chart reviews and fluoroscopic imaging. The procedural characteristics (thrombolytic drug dosage, treatment duration, and additional procedures), immediate angiographic outcomes (patency of calf vessels, and complete lysis), complications (major bleeding, and fasciotomy), and primary composite end-points (30-day mortality, amputation, and reocclusion) were compared between patients who received CDT versus PMT. RESULTS: Compared with CDT, PMT was independently associated with lower total UK dosage (standardized coefficient ß=- 0.44; P<0.01) and higher prevalence of complete lysis (odds ratio =1.78, 95% confidence interval: 1.03-3.06; P=0.04) after adjustments of covariates. The PMT group had significantly shorter treatment duration (23.00 [7.25-39.13] vs. 41.00 [27.00-52.50]; P<0.01). No significant intergroup differences were observed for the primary composite end point (10.7% vs. 9.1%; P=0.81), or prevalence of the major bleeding (9.1% vs. 0.0%; P=0.10) despite the PMT group comprising patients with more advanced chronic kidney disease and more diffuse thrombosis. CONCLUSIONS: PMT with a Rotarex is a safe and effective strategy for treating thrombotic or embolic lower limb ischemia. It significantly reduced the thrombolytic drug dosage, and resulted in the complete lysis being more likely.

Paradoxical mortality of high estimated glomerular filtration rate reversed by 24-h urine creatinine excretion rate adjustment: sarcopenia matters.

BACKGROUND: Muscle wasting may explain the paradoxical mortality of patients with high estimated glomerular filtration rates (eGFRs) derived from equation methods. However, empirical evidence and solutions remain insufficient. METHODS: In this retrospective cohort study, we compared the performance of equation methods for predicting all-cause mortality; we used 24-h creatinine clearance (24-h CrCl), equation-based eGFRs, and a new eGFR estimating equation weighting for population 24-h urine creatinine excretion rate (U-CER). From 2003 to 2018, we identified 4986 patients whose data constituted the first 24-h CrCl measurement data in the Clinical Research Data Repository of China Medical University Hospital and were followed up for at least 5 years after careful exclusion. Three GFR estimation equations [the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), Modification of Diet in Renal Disease (MDRD) Study, and Taiwanese MDRD], 24-h CrCl, and 24-h U-CER-adjusted eGFR were used. RESULTS: A high correlation was observed among the eGFR levels derived from the equation methods (0.995-1.000); however, the correlation decreased to 0.895-0.914 when equation methods were compared with the 24-h CrCl or 24-h U-CER-adjusted equation-based eGFR. In the Bland-Altman plots, the average discrepancy between the equation methods and the 24-h CrCl method was close to zero (maximal bias range: 5.12 for the Taiwanese MDRD equation vs. 24-h CrCl), but the range in limit of agreement was wide, from ±43.7 mL/min/1.73 m2 for the CKD-EPI equation to ±54.3 mL/min/1.73 m2 for the Taiwanese MDRD equation. A J-shaped dose-response relationship was observed between all equation-based eGFRs and all-cause mortality. Only 24-h CrCl exhibited a non-linear negative dose-response relationship with all-cause mortality. After adjustment for 24-h U-CER in the statistical model, the paradoxical increase in mortality risk for an eGFR of >90 mL/min/1.73 m2 returned to null. When 24-h U-CER was used directly to correct eGFR, the monotonic non-linear negative relationship with all-cause mortality was almost identical to that of 24-h CrCl. CONCLUSIONS: The 24-h U-CER-adjusted eGFR and 24-h CrCl are viable options for informing mortality risk. The 24-h U-CER adjustment method can be practically implemented to eGFR-based care and effectively mitigate the inherent confounding biases from individual's muscle mass amount due to both sex and racial differences.

Hybrid-Pattern Recognition Modeling with Arrhythmia Signal Processing for Ubiquitous Health Management.

We established a web-based ubiquitous health management (UHM) system, "ECG4UHM", for processing ECG signals with AI-enabled models to recognize hybrid arrhythmia patterns, including atrial premature atrial complex (APC), atrial fibrillation (AFib), ventricular premature complex (VPC), and ventricular tachycardia (VT), versus normal sinus rhythm (NSR). The analytical model coupled machine learning methods, such as multiple layer perceptron (MLP), random forest (RF), support vector machine (SVM), and naive Bayes (NB), to process the hybrid patterns of four arrhythmia symptoms for AI computation. The data pre-processing used Hilbert-Huang transform (HHT) with empirical mode decomposition to calculate ECGs' intrinsic mode functions (IMFs). The area centroids of the IMFs' marginal Hilbert spectrum were suggested as the HHT-based features. We engaged the MATLABTM compiler and runtime server in the ECG4UHM to build the recognition modules for driving AI computation to identify the arrhythmia symptoms. The modeling extracted the crucial data sets from the MIT-BIH arrhythmia open database. The validated models, including the premature pattern (i.e., APC-VPC) and the fibril-rapid pattern (i.e., AFib-VT) against NSR, could reach the best area under the curve (AUC) of the receiver operating characteristic (ROC) of approximately 0.99. The models for all hybrid patterns, without VPC versus AFib and VT, achieved an average accuracy of approximately 90%. With the prediction test, the respective AUCs of the NSR and APC versus the AFib, VPC, and VT were 0.94 and 0.93 for the RF and SVM on average. The average accuracy and the AUC of the MLP, RF, and SVM models for APC-VT reached the value of 0.98. The self-developed system with AI computation modeling can be the backend of the intelligent social-health system that can recognize hybrid arrhythmia patterns in the UHM and home-isolated cares.

Risk of All-Cause Mortality, Cardiovascular Disease Mortality, and Cancer Mortality in Patients With Bullous Pemphigoid.

IMPORTANCE: The role of bullous pemphigoid (BP) in cardiovascular disease (CVD) mortality remains controversial, and analyses of causes of death among patients with BP based on individual data remain lacking. OBJECTIVE: To evaluate the risk of all-cause mortality, CVD mortality, and cancer mortality in patients with BP. DESIGN, SETTING, AND PARTICIPANTS: This cohort study identified patients who received a diagnosis of and treatment for BP during their dermatology clinic visits at a tertiary medical center in central Taiwan between January 1, 2007, and December 31, 2017. Controls were patients without BP and were individually matched to cases (4:1) according to age, sex, and date of the dermatology clinic visit. Data were analyzed from March 6, 2019, to April 2, 2021. EXPOSURES: Bullous pemphigoid was confirmed pathologically with typical direct immunofluorescence findings or clinically with typical clinical presentation, positive findings of an anti-basement membrane zone antibody test, and corticosteroid use for at least 28 cumulative days. MAIN OUTCOMES AND MEASURES: Mortality outcomes confirmed by the National Death Registry. RESULTS: Of 252 patients with BP and 1008 matched control patients (N = 1260), 685 (54.4%) were men and the median age was 78.0 (IQR, 70.3-84.8) years. Patients with BP had higher CVD mortality at 1 year (20 [7.9%] vs 13 [1.3%]), 3 years (28 [11.1%] vs 24 [2.4%]), and 5 years (31 [12.3%] vs 39 [3.9%]) compared with matched control patients. After adjusting for potential confounding variables, patients with BP had a 5-fold higher risk of CVD mortality at 1 year (hazard ratio [HR], 5.29 [95% CI, 2.40-11.68]), 3 years (HR, 5.79 [95% CI, 3.11-10.78]), and 5 years (HR, 4.95 [95% CI, 2.88-8.51]). Subgroup analyses revealed that the CVD mortality risk associated with BP was higher in patients without a history of hypertension (HR, 7.28 [95% CI, 3.87-13.69]) or CVD (HR, 6.59 [95% CI, 3.40-12.79]) and in patients without prior diuretic use (HR, 5.75 [95% CI, 3.15-10.50]) compared with matched control patients. In addition, all-cause mortality associated with BP was higher in patients without prior corticosteroid use than in control patients (HR 5.65 [95% CI, 4.19-7.61]). CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that BP was associated with a 5-fold higher risk of CVD mortality, particularly in patients without underlying hypertension or CVD or those without prior corticosteroid or diuretic use. Future studies should investigate the benefits of routine monitoring and timely management of CVD symptoms and signs in patients with BP.

Associations between Myocardial Diastolic Dysfunction and Cardiovascular Mortality in Chronic Kidney Disease: A Large Single-Center Cohort Study.

BACKGROUND: The clinical burden and prognostic role of diastolic dysfunction (DD), on the basis of the latest (2016) American Society of Echocardiography guidelines, remain unclear in patients with chronic kidney disease (CKD). Moreover, risk mapping of concomitant systolic dysfunction and DD to evaluate the hazard of cardiovascular (CV) mortality in patients with CKD remains unexplored. METHODS: This retrospective cohort study identified 20,257 adult patients who underwent comprehensive echocardiography between 2008 and 2016 at a tertiary medical center in central Taiwan. The patients were stratified by CKD stage, and 3-year CV mortality risk in each CKD stratum was estimated through multivariable Cox proportional-hazards modeling using left ventricular ejection fraction (LVEF) and DD grades on the basis of the 2016 American Society of Echocardiography guidelines as the main risk factors. RESULTS: Compared with patients with stages 1 and 2 CKD, those with stages 4 and 5 CKD had significantly lower left ventricular ejection fractions and more severe DD. Both left ventricular ejection fraction (<40% vs ≥60%; adjusted hazard ratio, 3.17; 95% CI, 2.54-3.97) and DD grade (severe DD vs normal diastolic function; adjusted hazard ratio, 3.33; 95% CI, 2.33-4.76) were independently associated with 3-year CV mortality in the entire study population and had comparable effect sizes. The corresponding adjusted hazard ratios further increased to 4.20 (95% CI, 2.45-7.21) and 4.54 (95% CI, 2.20-9.38) in patients with stages 4 and 5 CKD. Systolic dysfunction and DD demonstrated mutually augmentative effects on CV mortality. CONCLUSIONS: These findings suggest that the current practice of cardioprotection for patients with CKD should be prioritized at an early stage along with conventional nephroprotection.

The association of arsenic exposure and arsenic metabolism with all-cause, cardiovascular and cancer mortality in the Strong Heart Study.

The effect of low-moderate levels of arsenic exposure and of arsenic metabolism on mortality remains uncertain. We used data from a prospective cohort study in 3600 men and women aged 45 to 75 years living in Arizona, Oklahoma, and North and South Dakota. The biomarker of inorganic arsenic exposure was the sum of urine inorganic (iAs), monomethylated (MMA) and dimethylated (DMA) arsenic compounds (Æ©As) at baseline. The proportions of urine iAs, MMA and DMA over the Æ©iAs, expressed as iAs%, MMA%, and DMA%, respectively, were used as biomarkers of arsenic metabolism. Arsenic exposure and arsenic metabolism were associated with all-cause, cardiovascular, and cancer mortality. For each interquartile range (IQR) increase in Æ©As (12.5 µg/L, overall range 0.7-194.1 µg/L), the adjusted hazard ratios (aHRs) were 1.28 (95% CI 1.16-1.41) for all-cause mortality, 1.28 (1.08-1.52) for cardiovascular mortality and 1.15 (0.92-1.44) for cancer mortality. The aHR for mortality for each IQR increase in MMA%, when iAs% is decreasing, was 1.52 (95% CI 1.16-1.99) for cardiovascular disease, 0.73 (0.55-0.98) for cancer, and 1.03 (0.90-1.19) for all-cause mortality. These findings at low-moderate levels of arsenic exposure highlight the need to implement public health measures to protect populations from involuntary arsenic exposure and for research to advance the biological and clinical understanding of arsenic-related health effects in general populations.

Diameter Reduction Determined Through Carotid Ultrasound Associated With Cardiovascular and All-Cause Mortality: A Single-Center Experience of 38 201 Consecutive Patients in Taiwan.

Background Few studies have evaluated the prognostic significance of diameter-based carotid sonographic measurements for mortality. We investigated whether a reduction in diameter of different carotid anatomical segments is associated with cardiovascular and all-cause mortality in a hospital-based cohort with universal health care. Methods and Results We conducted a retrospective cohort study of 38 201 patients who underwent carotid duplex ultrasound at a medical center in Taiwan. Carotid sonographic parameters were the diameter reduction percentage in carotid bifurcation, the internal carotid artery, the common carotid artery, and the external carotid artery and the overall carotid atherosclerotic burden score, determined by summing the scores from all segments. The vital status was ascertained by linking data to National Death Registry until 2017. During a median follow-up of 4.2 years, 5644 participants died, with 1719 deaths attributable to cardiovascular diseases. The multivariable-adjusted hazard ratios (HRs; 95% CIs) for cardiovascular mortality were 1.33 (1.16‒1.53), 1.58 (1.361.84), and 1.89 (1.58, 2.26) for participants with 30% to <40%, 40% to <50%, and ≥50% reduction in carotid bifurcation diameter, respectively, compared with participants with <30% diameter reduction (P for trend <0.001). The corresponding HRs (95% CIs) for all-cause mortality were 1.25 (1.16‒1.34), 1.42 (1.31‒1.54), and 1.60 (1.45‒1.77), respectively. Diameter reduction at other carotid sites and the carotid atherosclerotic burden score exhibited the same dose-response relationship. Conclusions This study suggests that reduction in carotid artery diameter, which can be determined through routinely available sonography, is an independent risk factor for all-cause and cardiovascular mortality.