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Background: The lack of automated tools for measuring care quality limits the implementation of a national program to assess guideline-directed care in heart failure with reduced ejection fraction (HFrEF)., Objectives: The authors aimed to automate the identification of patients with HFrEF at hospital discharge, an opportunity to evaluate and improve the quality of care., Methods: The authors developed a novel deep-learning language model for identifying patients with HFrEF from discharge summaries of hospitalizations with heart failure at Yale New Haven Hospital during 2015 to 2019. HFrEF was defined by left ventricular ejection fraction <40% on antecedent echocardiography. The authors externally validated the model at Northwestern Medicine, community hospitals of Yale, and the MIMIC-III (Medical Information Mart for Intensive Care III) database., Results: A total of 13,251 notes from 5,392 unique individuals (age 73 ± 14 years, 48% women), including 2,487 patients with HFrEF (46.1%), were used for model development (train/held-out: 70%/30%). The model achieved an area under receiver-operating characteristic curve (AUROC) of 0.97 and area under precision recall curve (AUPRC) of 0.97 in detecting HFrEF on the held-out set. The model had high performance in identifying HFrEF with AUROC = 0.94 and AUPRC = 0.91 on 19,242 notes from Northwestern Medicine, AUROC = 0.95 and AUPRC = 0.96 on 139 manually abstracted notes from Yale community hospitals, and AUROC = 0.91 and AUPRC = 0.92 on 146 manually reviewed notes from MIMIC-III. Model-based predictions of HFrEF corresponded to a net reclassification improvement of 60.2 ± 1.9% compared with diagnosis codes (P < 0.001)., Conclusions: The authors developed a language model that identifies HFrEF from clinical notes with high precision and accuracy, representing a key element in automating quality assessment for individuals with HFrEF., Competing Interests: Funding Support and Author Disclosures This study was supported by research funding awarded to Dr Khera by the Yale School of Medicine and grant support from the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) under the award K23HL153775. Dr Ahmad is a consultant for Sanofi Aventis, Amgen, and Cytokinetics; and has received research funding from Boehringer Ingelheim, AstraZeneca, Cytokinetics, and Relypsa. Dr Nadkarni has consultancy agreements with AstraZeneca, BioVie, GLG Consulting, Pensieve Health, Reata, Renalytix, Siemens Healthineers and Variant Bio; has received research funding from Goldfinch Bio, and Renalytix; has received honoraria from AstraZeneca, BioVie, Lexicon, Daiichi Sankyo, Meanrini Health, and Reata; has patents or royalties with Renalytix; owns equity and stock options in Pensieve Health and Renalytix as a scientific cofounder; owns equity in Verici Dx; has received financial compensation as a scientific board member and advisor to Renalytix; has served on the advisory board of Neurona Health; and has served in an advisory or leadership role for Pensieve Health and Renalytix. Dr Ahmad has received grants from the Agency for Healthcare Research and Quality, NIH/NHLBI, and American Heart Association; and has received personal fees from Teladoc, Livongo, and Pfizer, outside of the submitted work. Dr Krumholz works under contract with the Centers for Medicare and Medicaid Services to support quality measurement programs; was a recipient of a research grant from Johnson and Johnson, through Yale University, to support clinical trial data sharing; was a recipient of a research agreement, through Yale University, from the Shenzhen Center for Health Information for work to advance intelligent disease prevention and health promotion; collaborates with the National Center for Cardiovascular Diseases in Beijing; receives payment from the Arnold and Porter Law Firm for work related to the Sanofi clopidogrel litigation, from the Martin Baughman Law Firm for work related to the Cook Celect IVC filter litigation, and from the Siegfried and Jensen Law Firm for work related to Vioxx litigation; chairs a Cardiac Scientific Advisory Board for UnitedHealth; was a member of the IBM Watson Health Life Sciences Board; is a member of the Advisory Board for Element Science, the Advisory Board for Facebook, and the Physician Advisory Board for Aetna; and is the cofounder of Hugo Health, a personal health information platform, and cofounder of Refactor Health, a health care AI-augmented data management company. Dr Khera is an Associate Editor of JAMA; receives support from the NHLBI of the NIH (under awards R01HL167858 and K23HL153775) and the Doris Duke Charitable Foundation (under award 2022060); has received research support, through Yale, from Bristol Myers Squibb, Novo Nordisk, and BridgeBio; is a coinventor of U.S. Pending Patent Applications 63/562,335, 63/177,117, 63/428,569, 63/346,610, 63/484,426, 63/508,315, and 63/606,203; and is a co-founder of Ensight-AI, Inc and Evidence2Health, health platforms to improve cardiovascular diagnosis and evidence-based cardiovascular care. Dr Nargesi has received funding from the NHLBI under award number T32HL007604. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024. Published by Elsevier Inc.)

Background and Aims: Ectopic lipid storage is implicated in type 2 diabetes pathogenesis; hence, exercise to deplete stores (i.e., at the intensity that allows for maximal rate of lipid oxidation; MLO) might be optimal for restoring metabolic health. This intensity ("Fat max ") is estimated during incremental exercise ("Fat max test"). However, in "the field" general recommendations exist regarding a range of percentages of maximal heart rate (HR) to elicit MLO. The degree to which this range is aligned with measured Fat max has not been investigated. We compared measured HR at Fat max , with maximal HR percentages within the typically recommended range in a sample of 26 individuals (Female: n = 11, European ancestry: n = 17)., Methods and Results: Subjects completed a modified Fat max test with a 5-min warmup, followed by incremental stages starting at 15 W with work rate increased by 15 W every 5 min until termination criteria were reached. Pulmonary gas exchange was recorded and average values for V˙ o 2 and V˙ co 2 for the final minute of each stage were used to estimate substrate-oxidation rates. We modeled lipid-oxidation kinetics using a sinusoidal model and expressed MLO relative to peak V˙ o 2 and HR. Bland-Altman analysis demonstrated lack of concordance between HR at Fat max and at 50%, 70%, and 80% of age-predicted maximum with a mean difference of 23 b·min -1 ., Conclusion: Our results indicate that estimated "fat-burning" heart rate zones are inappropriate for prescribing exercise to elicit MLO and we recommend direct individual exercise lipid oxidation measurements to elicit these values., Competing Interests: Declaration of competing interest No conflicts of interest, financial or otherwise, are declared by the authors., (Copyright © 2023 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Binary diagnosis of coronary artery disease does not preserve the complexity of disease or quantify its severity or its associated risk with death; hence, a quantitative marker of coronary artery disease is warranted. We evaluated a quantitative marker of coronary artery disease derived from probabilities of a machine learning model., Methods: In this cohort study, we developed and validated a coronary artery disease-predictive machine learning model using 95 935 electronic health records and assessed its probabilities as in-silico scores for coronary artery disease (ISCAD; range 0 [lowest probability] to 1 [highest probability]) in participants in two longitudinal biobank cohorts. We measured the association of ISCAD with clinical outcomes-namely, coronary artery stenosis, obstructive coronary artery disease, multivessel coronary artery disease, all-cause death, and coronary artery disease sequelae., Findings: Among 95 935 participants, 35 749 were from the BioMe Biobank (median age 61 years [IQR 18]; 14 599 [41%] were male and 21 150 [59%] were female; 5130 [14%] were with diagnosed coronary artery disease) and 60 186 were from the UK Biobank (median age 62 [15] years; 25 031 [42%] male and 35 155 [58%] female; 8128 [14%] with diagnosed coronary artery disease). The model predicted coronary artery disease with an area under the receiver operating characteristic curve of 0·95 (95% CI 0·94-0·95; sensitivity of 0·94 [0·94-0·95] and specificity of 0·82 [0·81-0·83]) and 0·93 (0·92-0·93; sensitivity of 0·90 [0·89-0·90] and specificity of 0·88 [0·87-0·88]) in the BioMe validation and holdout sets, respectively, and 0·91 (0·91-0·91; sensitivity of 0·84 [0·83-0·84] and specificity of 0·83 [0·82-0·83]) in the UK Biobank external test set. ISCAD captured coronary artery disease risk from known risk factors, pooled cohort equations, and polygenic risk scores. Coronary artery stenosis increased quantitatively with ascending ISCAD quartiles (increase per quartile of 12 percentage points), including risk of obstructive coronary artery disease, multivessel coronary artery disease, and stenosis of major coronary arteries. Hazard ratios (HRs) and prevalence of all-cause death increased stepwise over ISCAD deciles (decile 1: HR 1·0 [95% CI 1·0-1·0], 0·2% prevalence; decile 6: 11 [3·9-31], 3·1% prevalence; and decile 10: 56 [20-158], 11% prevalence). A similar trend was observed for recurrent myocardial infarction. 12 (46%) undiagnosed individuals with high ISCAD (≥0·9) had clinical evidence of coronary artery disease according to the 2014 American College of Cardiology/American Heart Association Task Force guidelines., Interpretation: Electronic health record-based machine learning was used to generate an in-silico marker for coronary artery disease that can non-invasively quantify atherosclerosis and risk of death on a continuous spectrum, and identify underdiagnosed individuals., Funding: National Institutes of Health., Competing Interests: Declaration of interests RD reported receiving grants from AstraZeneca; grants and non-financial support from Goldfinch Bio; being a scientific co-founder, consultant, and equity holder for Pensieve Health; and being a consultant for Variant Bio, outside of the submitted work. GNN reported being a scientific co-founder, consultant, advisory board member, and equity owner of Renalytix AI; a scientific co-founder and equity holder for Pensieve Health; a consultant for Variant Bio; and received grants from Goldfinch Bio and personal fees from Renalytix AI, BioVie, Reata, AstraZeneca, and GLG Consulting, outside of the submitted work. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Estimated glomerular filtration rate (eGFR) reflects kidney function. Progressive eGFR-decline can lead to kidney failure, necessitating dialysis or transplantation. Hundreds of loci from genome-wide association studies (GWAS) for eGFR help explain population cross section variability. Since the contribution of these or other loci to eGFR-decline remains largely unknown, we derived GWAS for annual eGFR-decline and meta-analyzed 62 longitudinal studies with eGFR assessed twice over time in all 343,339 individuals and in high-risk groups. We also explored different covariate adjustment. Twelve genome-wide significant independent variants for eGFR-decline unadjusted or adjusted for eGFR-baseline (11 novel, one known for this phenotype), including nine variants robustly associated across models were identified. All loci for eGFR-decline were known for cross-sectional eGFR and thus distinguished a subgroup of eGFR loci. Seven of the nine variants showed variant-by-age interaction on eGFR cross section (further about 350,000 individuals), which linked genetic associations for eGFR-decline with age-dependency of genetic cross-section associations. Clinically important were two to four-fold greater genetic effects on eGFR-decline in high-risk subgroups. Five variants associated also with chronic kidney disease progression mapped to genes with functional in-silico evidence (UMOD, SPATA7, GALNTL5, TPPP). An unfavorable versus favorable nine-variant genetic profile showed increased risk odds ratios of 1.35 for kidney failure (95% confidence intervals 1.03-1.77) and 1.27 for acute kidney injury (95% confidence intervals 1.08-1.50) in over 2000 cases each, with matched controls). Thus, we provide a large data resource, genetic loci, and prioritized genes for kidney function decline, which help inform drug development pipelines revealing important insights into the age-dependency of kidney function genetics., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Rationale and Objective: APOL1 risk alleles are associated with increased cardiovascular and chronic kidney disease (CKD) risk. It is unknown whether knowledge of APOL1 risk status motivates patients and providers to attain recommended blood pressure (BP) targets to reduce cardiovascular disease., Study Design: Multicenter, pragmatic, randomized controlled clinical trial., Setting and Participants: 6650 individuals with African ancestry and hypertension from 13 health systems., Intervention: APOL1 genotyping with clinical decision support (CDS) results are returned to participants and providers immediately (intervention) or at 6 months (control). A subset of participants are re-randomized to pharmacogenomic testing for relevant antihypertensive medications (pharmacogenomic sub-study). CDS alerts encourage appropriate CKD screening and antihypertensive agent use., Outcomes: Blood pressure and surveys are assessed at baseline, 3 and 6 months. The primary outcome is change in systolic BP from enrollment to 3 months in individuals with two APOL1 risk alleles. Secondary outcomes include new diagnoses of CKD, systolic blood pressure at 6 months, diastolic BP, and survey results. The pharmacogenomic sub-study will evaluate the relationship of pharmacogenomic genotype and change in systolic BP between baseline and 3 months., Results: To date, the trial has enrolled 3423 participants., Conclusions: The effect of patient and provider knowledge of APOL1 genotype on systolic blood pressure has not been well-studied. GUARDD-US addresses whether blood pressure improves when patients and providers have this information. GUARDD-US provides a CDS framework for primary care and specialty clinics to incorporate APOL1 genetic risk and pharmacogenomic prescribing in the electronic health record., Trial Registration: ClinicalTrials.govNCT04191824., (Copyright © 2022. Published by Elsevier Inc.)

Objective: To characterize continuous video electroencephalogram (VEEG) findings of hospitalized COVID-19 patients., Methods: We performed a retrospective chart review of patients admitted at three New York City hospitals who underwent VEEG at the peak of the COVID-19 pandemic. Demographics, comorbidities, neuroimaging, VEEG indications and findings, treatment, and outcomes were collected., Results: Of 93 patients monitored, 77% had severe COVID-19 and 40% died. Acute ischemic or hemorrhagic stroke was present in 26% and 15%, respectively. Most common VEEG indications were encephalopathy/coma (60%) and seizure-like movements (38%). Most common VEEG findings were generalized slowing (97%), generalized attenuation (31%), generalized periodic discharges (17%) and generalized sharp waves (15%). Epileptiform abnormalities were present in 43% and seizures in 8% of patients, all of whom had seizure risk factors. Factors associated with an epileptiform VEEG included increasing age (OR 1.07, p = 0.001) and hepatic/renal failure (OR 2.99, p = 0.03)., Conclusions: Most COVID-19 patients who underwent VEEG monitoring had severe COVID-19 and over one-third had acute cerebral injury (e.g., stroke, anoxia). Seizures were uncommon. VEEG findings were nonspecific., Significance: VEEG findings in this cohort of hospitalized COVID-19 patients were those often seen in critical illness. Seizures were uncommon and occurred in the setting of common seizure risk factors., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Objectives: This study sought to develop DL models capable of comprehensively quantifying left and right ventricular dysfunction from ECG data in a large, diverse population., Background: Rapid evaluation of left and right ventricular function using deep learning (DL) on electrocardiograms (ECGs) can assist diagnostic workflow. However, DL tools to estimate right ventricular (RV) function do not exist, whereas those to estimate left ventricular (LV) function are restricted to quantification of very low LV function only., Methods: A multicenter study was conducted with data from 5 New York City hospitals: 4 for internal testing and 1 serving as external validation. We created novel DL models to classify left ventricular ejection fraction (LVEF) into categories derived from the latest universal definition of heart failure, estimate LVEF through regression, and predict a composite outcome of either RV systolic dysfunction or RV dilation., Results: We obtained echocardiogram LVEF estimates for 147,636 patients paired to 715,890 ECGs. We used natural language processing (NLP) to extract RV size and systolic function information from 404,502 echocardiogram reports paired to 761,510 ECGs for 148,227 patients. For LVEF classification in internal testing, area under curve (AUC) at detection of LVEF ≤40%, 40% < LVEF ≤50%, and LVEF >50% was 0.94 (95% CI: 0.94-0.94), 0.82 (95% CI: 0.81-0.83), and 0.89 (95% CI: 0.89-0.89), respectively. For external validation, these results were 0.94 (95% CI: 0.94-0.95), 0.73 (95% CI: 0.72-0.74), and 0.87 (95% CI: 0.87-0.88). For regression, the mean absolute error was 5.84% (95% CI: 5.82%-5.85%) for internal testing and 6.14% (95% CI: 6.13%-6.16%) in external validation. For prediction of the composite RV outcome, AUC was 0.84 (95% CI: 0.84-0.84) in both internal testing and external validation., Conclusions: DL on ECG data can be used to create inexpensive screening, diagnostic, and predictive tools for both LV and RV dysfunction. Such tools may bridge the applicability of ECGs and echocardiography and enable prioritization of patients for further interventions for either sided failure progressing to biventricular disease., Competing Interests: Funding Support and Author Disclosures This study was supported by the National Center for Advancing Translational Sciences, National Institutes of Health (U54 TR001433-05). This study has been approved by the institutional review board at the Icahn School of Medicine at Mount Sinai. Dr Nadkarni is supported by National Institutes of Health grants: R01DK127139 from NIDDK and R01HL155915 from NHLBI. Dr Somani is a co-founder of and owns equity in Monogram Orthopedics. Dr Johnson is an employee of Tempus, Inc. Dr Nadkarni is a scientific co-founder, consultant, advisory board member, and equity owner of Renalytix AI; a scientific co-founder and equity holder for Pensieve Health; a consultant for Variant Bio; and received grants from Goldfinch Bio and personal fees from Renalytix AI, BioVie, Reata, AstraZeneca, and GLG Consulting. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m 2 /year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m 2 at follow-up among those with eGFRcrea 60 mL/min/1.73m 2 or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or LARP4B. Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function., (Copyright © 2020 International Society of Nephrology. All rights reserved.)

Urinary tract stones have high heritability indicating a strong genetic component. However, genome-wide association studies (GWAS) have uncovered only a few genome wide significant single nucleotide polymorphisms (SNPs). Polygenic risk scores (PRS) sum cumulative effect of many SNPs and shed light on underlying genetic architecture. Using GWAS summary statistics from 361,141 participants in the United Kingdom Biobank, we generated a PRS and determined association with stone diagnosis in 28,877 participants in the Mount Sinai BioMe Biobank. In BioMe (1,071 cases and 27,806 controls), for every standard deviation increase, we observed a significant increment in adjusted odds ratio of a factor of 1.2 (95% confidence interval 1.13-1.26). In comparison, a risk score comprised of GWAS significant SNPs was not significantly associated with diagnosis. After stratifying individuals into low and high-risk categories on clinical risk factors, there was a significant increment in adjusted odds ratio of 1.3 (1.12-1.6) in the low- and 1.2 (1.1-1.2) in the high-risk group for every standard deviation increment in PRS. In a 14,348-participant validation cohort (Penn Medicine Biobank), every standard deviation increment was associated with a significant adjusted odds ratio of 1.1 (1.03 - 1.2). Thus, a genome-wide PRS is associated with urinary tract stones overall and in the absence of known clinical risk factors and illustrates their complex polygenic architecture., (Copyright © 2020 International Society of Nephrology. All rights reserved.)

Symptoms are common in patients on maintenance hemodialysis but identification is challenging. New informatics approaches including natural language processing (NLP) can be utilized to identify symptoms from narrative clinical documentation. Here we utilized NLP to identify seven patient symptoms from notes of maintenance hemodialysis patients of the BioMe Biobank and validated our findings using a separate cohort and the MIMIC-III database. NLP performance was compared for symptom detection with International Classification of Diseases (ICD)-9/10 codes and the performance of both methods were validated against manual chart review. From 1034 and 519 hemodialysis patients within BioMe and MIMIC-III databases, respectively, the most frequently identified symptoms by NLP were fatigue, pain, and nausea/vomiting. In BioMe, sensitivity for NLP (0.85 - 0.99) was higher than for ICD codes (0.09 - 0.59) for all symptoms with similar results in the BioMe validation cohort and MIMIC-III. ICD codes were significantly more specific for nausea/vomiting in BioMe and more specific for fatigue, depression, and pain in the MIMIC-III database. A majority of patients in both cohorts had four or more symptoms. Patients with more symptoms identified by NLP, ICD, and chart review had more clinical encounters. NLP had higher specificity in inpatient notes but higher sensitivity in outpatient notes and performed similarly across pain severity subgroups. Thus, NLP had higher sensitivity compared to ICD codes for identification of seven common hemodialysis-related symptoms, with comparable specificity between the two methods. Hence, NLP may be useful for the high-throughput identification of patient-centered outcomes when using electronic health records., (Copyright © 2019 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Ethnic disparities in health outcomes exist among multiple complex diseases especially cardiovascular disease, hypertension, and kidney disease. Recent discoveries in genetics have taught us that these disparities go beyond environmental and socioeconomic factors. The discovery of ethnic-specific risk variants in the Apolipoprotein L1 (APOL1) gene on chromosome 22 seen only in individuals of recent African ancestry explains a large proportion of kidney disease disparities. In addition, recent large-scale genotype-phenotype association studies have identified associations with cardiovascular disease and hypertension. This review aims to review the recent literature in this field and point toward future directions for research., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Novel biomarkers are needed to predict kidney function decline in patients with type 2 diabetes, especially those with preserved glomerular filtration rate (GFR). There are limited data on the association of markers of endothelial dysfunction with longitudinal GFR decline. We used banked specimens from a nested case-control study in the Action to Control Cardiovascular Disease (ACCORD) trial (n=187 cases: 187 controls) and from a diverse contemporary cohort of type 2 diabetic patients from the Mount Sinai BioMe Biobank (n=871) to assess the association of plasma endostatin and kidney outcomes. We measured plasma endostatin at enrollment and examined its association with a composite kidney outcome of sustained 40% decline in estimated GFR or end-stage renal disease. Baseline plasma endostatin levels were higher in participants with the composite outcome. Each log 2 increment in plasma endostatin was associated with approximately 2.5-fold higher risk of the kidney outcome (adjusted odds ratio [OR] 2.5; 95% confidence interval [CI] 1.5-4.3 in ACCORD and adjusted hazard ratio [HR] 2.6; 95% CI 1.8-3.8 in BioMe). Participants in the highest vs. lowest quartile of plasma endostatin had approximately four-fold higher risk for the kidney outcome (adjusted OR 3.6; 95% CI 1.8-7.3 in ACCORD and adjusted HR 4.4; 95% CI 2.3-8.5 in BioMe). The AUC for the kidney outcome improved from 0.74 to 0.77 in BioMe with the addition of endostatin to a base clinical model. Plasma endostatin was strongly associated with kidney outcomes in type 2 diabetics with preserved eGFR and improved risk discrimination over traditional predictors., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

G1/G2 variants in the Apolipoprotein L1 (APOL1) gene are associated with end-stage renal disease (ESRD) in people with African ancestry. Plasma biomarkers may have utility for risk stratification in APOL1 high-risk individuals of African ancestry. To evaluate this, we measured tumor necrosis factor receptor 1/2 (TNFR1/2) and kidney injury molecule-1 (KIM1) in baseline plasma specimens from individuals of African ancestry with high-risk APOL1 genotype. Biomarker association with a composite renal outcome of ESRD or 40% sustained decline in estimated glomerular filtration rate (eGFR) was then determined and then assessed as improvement in area under curve. Among the 498 participants, the median age was 56 years, 67.7% were female, and the baseline eGFR was 83.3 ml/min/1.73 m 2 with 80 reaching outcome over 5.9 years. TNFR1, TNFR2, and KIM1 at enrollment were independently associated with renal outcome continuously (adjusted hazard ratio 2.0 [95% confidence interval 1.3-3.1]; 1.5 [1.2-1.9]; and 1.6 [1.3-1.9] per doubling in levels, respectively) or by tertiles. The area under the curve significantly improved from 0.75 with the clinical model to 0.79 with the biomarker-enhanced model. The event rate was 40% with all 3 biomarkers elevated (adjusted odds ratio of 5.3 (2.3-12.0) vs. 17% (adjusted odds ratio 1.8 [0.9-3.6] with 1 or 2 elevated and 7% with no biomarkers elevated. Thus, plasma concentrations of TNFR1, TNFR2, and KIM1 are independently associated with renal outcome and improve discrimination or reclassification of African ancestry individuals with a high-risk APOL1 genotype and preserve renal function. Elevation of all markers had higher risk of outcome and can assist with better clinical prediction and improved clinical trial efficiency by enriching event rates., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

HLA matching and mismatching, while inversely related, are not exact opposites. Here we determined the independent effects of HLA matching and mismatching on outcomes in deceased donor kidney transplant recipients. The United Network for Organ Sharing database (1995-2012) was utilized and analyzed for delayed graft function, one-year acute rejection, and death-censored graft survival using combined multivariable models including HLA matching and mismatching. Sensitivity analyses were performed using the subgroup of deceased donor kidney transplant patients after 2003 with more uniform HLA nomenclature and resampling analyses using bootstrapping on complete data available from 96,236 recipients. Individually, both HLA matching and mismatching showed significant associations with graft survival. Adjusting the model to take into account both matching and mismatching simultaneously, the degree of HLA mismatching lost significance while matching continued to have a significant prediction for delayed graft function, the one-year acute rejection rate, and graft survival. Sensitivity analyses and bootstrapping showed similar results for all studied outcomes. Thus, analysis of this large cohort demonstrates the apparent greater association of HLA matching over HLA mismatching on both early allograft events as well as graft survival. Future analyses should preferentially utilize HLA matching as a covariate over mismatching for accurately reflecting impact on graft outcomes., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to describe the temporal trends and outcomes of endovascular and surgical revascularization in a large, nationally representative sample of patients with end-stage renal disease on hemodialysis hospitalized for peripheral artery disease (PAD)., Background: PAD is prevalent among patients with end-stage renal disease on hemodialysis and is associated with significant morbidity and mortality. There is a paucity of information on trends in endovascular and surgical revascularization and post-procedure outcomes in this population., Methods: We used the Nationwide Inpatient Sample (2002 to 2012) to identify hemodialysis patients undergoing endovascular or surgical procedures for PAD using diagnostic and procedural codes. We compared trends in amputation, post-procedure complications, mortality, length of stay, and costs between the 2 groups using trend tests and logistic regression., Results: There were 77,049 endovascular and 29,556 surgical procedures for PAD in hemodialysis patients. Trend analysis showed that endovascular procedures increased by nearly 3-fold, whereas there was a reciprocal decrease in surgical revascularization. Post-procedure complication rates were relatively stable in persons undergoing endovascular procedures but nearly doubled in those undergoing surgery. Surgery was associated with 1.8 times adjusted odds (95% confidence interval: 1.60 to 2.02) for complications and 1.6 times the adjusted odds for amputations (95% confidence interval: 1.40 to 1.75) but had similar mortality (adjusted odds ratio: 1.05; 95% confidence interval: 0.85 to 1.29) compared with endovascular procedures. Length of stay for endovascular procedures remained stable, whereas a decrease was seen for surgical procedures. Overall costs increased marginally for both procedures., Conclusions: Rates of endovascular procedures have increased, whereas those of surgeries have decreased. Surgical revascularization is associated with higher odds of overall complications. Further prospective studies and clinical trials are required to analyze the relationship between the severity of PAD and the revascularization strategy chosen., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

APOL1 risk variants have been shown to be associated with kidney disease and hypertension. In this study, Chen and colleagues assess the association of these risk variants with longitudinal blood pressure in young adults. We review the current literature on association of these alleles with blood pressure and propose future directions to resolve the existing controversies., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Chronic kidney disease (CKD), a progressive loss of renal function, can lead to serious complications if underdiagnosed. Many studies suggest that the oral microbiota plays important role in the health of the host; however, little is known about the association between the oral microbiota and CKD pathogenesis., Methods: In this study, we surveyed the oral microbiota in saliva, the left and right molars, and the anterior mandibular lingual area from 77 participants (18 with and 59 without CKD), and tested their association with CKD to identify microbial features that may be predictive of CKD status., Results: The overall oral microbiota composition significantly differed by oral locations and was associated with CKD status in saliva and anterior mandibular lingual samples. In CKD patients, we observed a significant enrichment of Neisseria and depletion of Veillonella in both sample types and a lower prevalence of Streptococcus in saliva after adjustment for other comorbidities. Furthermore, we detected a negative association of Neisseria and Streptococcus genera with the kidney function as measured by estimated glomerular filtration rate. Neisseria abundance also correlated with plasma interleukin-18 levels., Conclusion: We demonstrate the association of the oral microbiome with CKD and inflammatory kidney biomarkers, highlighting a potential role of the commensal bacteria in CKD pathogenesis. A better understanding of the interplay between the oral microbiota and CKD may help in the development of new strategies to identify at-risk individuals or to serve as a novel target for therapeutic intervention.

Ethnicity-specific differences in apolipoprotein L1 (APOL1) polymorphisms are associated with racial disparities in kidney transplantation outcomes. APOL1 genotyping may better help define graft outcome risk pre-transplantation; however, more research is needed., (Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Data from the electronic health records hold great promise for nephrology research. However, due to significant limitations, reporting guidelines have been formulated for analyses conducted using electronic health records data., (Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

A major role of the kidneys is to maintain phosphorus homeostasis. High serum phosphorus has been linked to all-cause and cardiovascular mortality in chronic kidney disease (CKD) both before and after initiation of renal replacement therapy. Considering the clinical implications of uncontrolled hyperphosphatemia, maintenance of phosphorus concentrations within an optimum range is standard of care in this patient population. Recently, the epidemiologic associations between serum phosphorus and worse outcome have been extended to the general population. This becomes even more important in view of the increasing dietary phosphorus intake in the American diet due in large part to the greater consumption of foods processed with phosphate additives. A greater understanding of mechanisms and epidemiology of altered phosphorus metabolism and disease in CKD may help clarify the possible role of excess dietary phosphorus as a health risk factor in the general population.

A 69-year man presented with 3 days of progressively worsening abdominal pain, radiating to his back, with nausea and vomiting. Computed tomography scan of the abdomen showed evidence of aortitis, for which he eventually underwent surgery. The surgical specimen of the aorta grew Clostridium septicum that was treated with antibiotics.

Background: Recent studies have shown that hypertension is inversely correlated with bone mineral density (BMD) as determined by dual energy x-ray absorptiometery (DXA) in different ethnic groups. But in most published studies, either the sample size was small or the study was limited by different measurement methods. These limitations leave this association controversial and inconclusive. The current study utilizes a sample of African American females referred for clinical screening of osteoporosis in our center to find out if any association of high blood pressure and BMD in this ethnic group exists. The secondary endpoint was to determine the effect of thiazide diuretics on BMD of the elderly African American females because, theoretically, thiazides are considered to have a positive impact on BMD., Methods: In this retrospective, cross-sectional study, 10 years of data were reviewed from 1113 medical records of African American females aged 65 years and older whose BMD values were measured by DXA at the lumbar spine (L1-L4) and both femoral necks (the standard sites for BMD determination) along with their T scores and Z scores (used to determine osteopenia vs osteoporosis). Our exclusion criteria included patients who: (1) were current smokers, (2) had a previous oophorectomy, (3) had a history of corticosteroid use, (4) had a history of biphosphonate use, (5) were on hormone replacement therapy, and (6) were diabetic and taking either pioglitazones or roziglitazones. A total of 148 patients were excluded from the analysis due to either incomplete data or exclusion criteria. The remaining sample was then divided into 2 groups based on their hypertensive status. For the subanalysis, the hypertensive group was further divided into 2 additional groups based on their thiazide usage., Results: We had complete data on 965 participants, of which 631 (65.3%) had a history of hypertension and 334 (34.7%) did not. Out of 631 hypertensive patients, 173 were found to be using thiazide diuretics as antihypertensive medication, while 458 were without thiazide diurectic use. The proportion of patients with both osteopenia and osteoporosis was similar in those with and without hypertension (50% vs 50%, p = .95 for osteopenia; 18% vs 19%, p = .95 for osteoporosis). There was no significant difference between the BMD at the lumbar spine, and right and left femoral necks between patients with and without hypertension. This lack of association held true when comparing the mean T scores and Z scores at the above sites. Within patients with a history of hypertension, there were no significant differences in the BMD, T score or Z score at any site with and without a history of thiazide diuretic use., Conclusion: Hypertension in elderly African American females aged at least 65 years was not found to be correlated with low BMD at either the lumbar spine (L1-L4) or both femoral necks when confounding factors were taken into consideration. Mean BMD of the hypertensive cohort taking thiazide diuretics was found lower at the lumbar spine as compared to the hypertensive patients not taking thiazide diuretics.

Background: Most studies of catheter ablation for the treatment of ventricular tachycardia (VT) are relatively small observational trials., Objective: The purpose of this study was to define the relative risk of VT recurrence in patients undergoing catheter ablation as an adjunct to medical therapy versus medical therapy alone in a pooled analysis of controlled studies., Methods: Randomized and nonrandomized controlled trials of patients who underwent adjunctive catheter ablation of VT versus medical therapy alone were sought. MEDLINE, EMBASE, the Cochrane central register of controlled trials (CENTRAL), and Web of Science were searched from 1965 to July 2010. Supplemental searches included Internet resources, reference lists, and reports of arrhythmia experts. Three authors independently reviewed and extracted the data regarding baseline characteristics, ablation methodology, medical therapy, complications, VT recurrences, mortality, and study quality., Results: Five studies were included totaling 457 participants with structural heart disease. Adjunctive catheter ablation was performed in 58% of participants, whereas 42% received medical therapy alone for VT. Complications of catheter ablation included death (1%), stroke (1%), cardiac perforation (1%), and complete heart block (1.6%). Using a random-effects model, a statistically significant 35% reduction in the number of patients with VT recurrence was noted with adjunctive catheter ablation (P<.001). There was no statistically significant difference in mortality., Conclusions: Catheter ablation as an adjunct to medical therapy reduces VT recurrences in patients with structural heart disease and has no impact on mortality., (Copyright © 2011 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Increase in pulse pressure has been shown to be predisposing factor for Coronary Artery Disease (CAD) in diverse patient populations but its relationship with the severity of CAD, particularly in the South Asians immigrant population of United States has not been demonstrated. We performed a single-center, cross-sectional study. Pulse pressure was calculated by the difference between the systolic and diastolic brachial blood pressures, and the Friesinger score (FS) was used to quantify the severity of CAD with the score of 5 used as a cutoff for extensive disease. We also sought to assess the correlation between the Friesinger score and the 10-year cardiovascular event (CVD) risk as calculated by the Framingham score. Odds ratios and 95% confidence intervals for the associations between explanatory variables and a high Friesinger score were estimated using multivariate logistic regression models. P values below .05 were considered to be statistically significant. Statistical analysis was performed using STATA version 10 software package (College Station, TX). The mean pulse pressure was significantly higher in participants with an FS of > or =5 compared with participants with an FS of <5 (63 vs. 46 mm Hg; P = .004). In univariate analysis, a pulse pressure > or =40 mm Hg was associated with a five-fold increased odds of a higher FS compared with a pulse pressure <40 mm Hg (P = .039), which was unchanged in multivariate analysis. In multivariate analysis, even after adjustment for presence of hypertension, a 10 mm Hg increase in pulse pressure was associated with a 1.97-fold increased odds of a higher FS (95% CI 1.22-3.71, P = .009). The mean Framingham score was higher in participants with a higher FS, but this difference was not significant (32.7 vs. 20.3; P = .1139). Our study demonstrates that pulse pressure, a well-established marker of vascular health, is a significant independent predictor of the severity of CAD as assessed by coronary angiography in South Asians., (Copyright (c) 2010 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.)