Treatment Effect Heterogeneity in Acute Kidney Injury Incidence Following Intravenous Antihypertensive Administration for Severe Blood Pressure Elevation During Hospitalization.

Rationale & Objective: Severe hypertension (sHTN) that develops after hospital admission is prevalent in 10% of patients admitted for reasons other than HTN. sHTN is commonly treated with intravenous (IV) antihypertensives and is associated with a greater risk of acute kidney injury (AKI). Our goal was to explore whether there is heterogeneity in IV antihypertensives' effect on AKI incidence among patients who develop sHTN during hospitalization.

Using Overlap Weights to Address Extreme Propensity Scores in Estimating Restricted Mean Counterfactual Survival Times.

While inverse probability of treatment weighting (IPTW) is a commonly used approach for treatment comparisons in observational data, the resulting estimates may be subject to bias and excessively large variance under lack of overlap. By smoothly down-weighting units with extreme propensity scores, i.e.

Neural network analysis as a novel skin outcome in a trial of belumosudil in patients with systemic sclerosis.

Background: The modified Rodnan skin score (mRSS), used to measure dermal thickness in patients with systemic sclerosis (SSc), is agnostic to inflammation and vasculopathy. Previously, we demonstrated the potential of neural network-based digital pathology applied to stained skin biopsies from SSc patients as a quantitative outcome. We leveraged deep learning and histologic analyses of clinical trial biopsies to decipher SSc skin features 'seen' by artificial intelligence (AI).

Early, Individualized Recommendations for Hospitalized Patients With Acute Kidney Injury: A Randomized Clinical Trial.

Importance: Acute kidney injury (AKI) is a common complication during hospitalization and is associated with adverse outcomes.

Objective: To evaluate whether diagnostic and therapeutic recommendations sent by a kidney action team through the electronic health record improve outcomes among patients hospitalized with AKI compared with usual care.

Design, Setting, And Participants: Randomized clinical trial conducted at 7 hospitals in 2 health systems: in New Haven, Bridgeport, New London, and Waterbury, Connecticut, and Westerly, Rhode Island; and in Baltimore, Maryland.

Mechanistic Differences between Torsemide and Furosemide.

Key Points: Oral torsemide was not superior to furosemide in measures of renal tubular delivery or duration of action. A dose equivalence of approximately 40 mg oral furosemide:10 mg oral torsemide resulted in similar natriuresis. The two-fold higher doses of torsemide did not improve fluid status due to the kidney’s compensation.

Incidence of Acute Kidney Injury and Associated Mortality among Individuals with Drug-Susceptible Tuberculosis in Uganda.

Key Points: AKI is thought to be a rare complication in patients with tuberculosis (TB) infection and is mostly attributed to TB drugs. Our findings show AKI occurs more often than previously thought and approximately 33% of patients with drug-susceptible TB may have kidney dysfunction. According to our study findings, monitoring kidney function should be routine among patients diagnosed with TB even before treatment initiation.

Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis.

Introduction: Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease leading to end-stage kidney disease (ESKD), is characterized by podocyte injury and depletion, whereas minimal change disease (MCD) has better outcomes despite podocyte injury. Identifying mechanisms capable of preventing podocytopenia during injury could transform FSGS to an "MCD-like" state. Preclinical data have reported conversion of an MCD-like injury to one with podocytopenia and FSGS by inhibition of AMP-kinase (AMPK) in podocytes.

Pragmatic Trial of Messaging to Providers About Treatment of Hyperlipidemia (PROMPT-LIPID): A Randomized Clinical Trial.

Background: Lipid-lowering therapy (LLT) is underutilized for very high-risk atherosclerotic cardiovascular disease. PROMPT-LIPID (PRagmatic Trial of Messaging to Providers about Treatment of HyperLIPIDemia) sought to determine whether electronic health record (EHR) alerts improve 90-day LLT intensification in patients with very high-risk atherosclerotic cardiovascular disease.

Methods: PROMPT-LIPID was a pragmatic trial in which cardiovascular and internal medicine clinicians within Yale New Haven Health (New Haven, CT) were cluster-randomized to receive an EHR alert with individualized LLT recommendations or no alert for outpatients with very high-risk atherosclerotic cardiovascular disease and LDL-C (low-density lipoprotein cholesterol), ≥70 mg/dL.

Serial direct sodium removal in patients with heart failure and diuretic resistance.

Aims: Loop diuretics may exacerbate cardiorenal syndrome (CRS) in heart failure (HF). Direct sodium removal (DSR) using the peritoneal membrane, in conjunction with complete diuretic withdrawal, may improve CRS and diuretic resistance.

Methods And Results: Patients with HF requiring high-dose loop diuretics were enrolled in two prospective, single-arm studies: RED DESERT (n = 8 euvolaemic patients), and SAHARA (n = 10 hypervolaemic patients).

COVID-19-Associated Acute Kidney Injury and Longitudinal Kidney Outcomes.

Importance: COVID-19 infection is associated with a high incidence of acute kidney injury (AKI). Although rapid kidney function decline has been reported in the first few months after COVID-19-associated AKI (COVID-AKI), the longer-term association of COVID-AKI with kidney function remains unknown.

Objective: To assess long-term kidney outcomes of patients who had COVID-19-associated AKI.

Deep learning prediction of hospital readmissions for asthma and COPD.

Question: Severe asthma and COPD exacerbations requiring hospitalization are linked to increased disease morbidity and healthcare costs. We sought to identify Electronic Health Record (EHR) features of severe asthma and COPD exacerbations and evaluate the performance of four machine learning (ML) and one deep learning (DL) model in predicting readmissions using EHR data.

Study Design And Methods: Observational study between September 30, 2012, and December 31, 2017, of patients hospitalized with asthma and COPD exacerbations.

Impact of Digital Health Technology on Quality of Life in Patients With Heart Failure.

Background: Digital health tools may improve quality of life (QoL) in patients with heart failure (HF) by promoting self-care, knowledge, and engagement.

Objectives: This study evaluates the effect of 3 digital technologies on QoL in patients with HF.

Methods: A total of 182 patients were randomized to usual care or one of the technologies promoting self-care: Bodyport (cardiac scale), Conversa (conversational platform), or Noom (smartphone application).

Rationale, Design, and Patient Characteristics of a Cluster-Randomized Pragmatic Trial to Improve Mineralocorticoid Antagonist Use.

Background: Despite robust evidence and strong guideline recommendations supporting use of mineralocorticoid receptor antagonists (MRAs) to improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF), these medications remain underused in clinical practice.

Objectives: The goal is to determine if providing a tailored best practice alert (BPA) to outpatient providers suggesting guideline-recommended MRAs or information about available hyperkalemia treatment, if present, for patients with HFrEF will increase short-term MRA prescriptions.

Methods: PROMPT-MRA (Pragmatic Trial of Messaging to Providers About Treatment With Mineralocorticoid Receptor Antagonists) is a pragmatic, cluster-randomized, controlled study.

Differences in Mortality Among Patients With Asthma and COPD Hospitalized With COVID-19.

Background: It remains unclear whether patients with asthma and/or chronic obstructive pulmonary disease (COPD) are at increased risk for severe coronavirus disease 2019 (COVID-19).

Objective: Compare in-hospital COVID-19 outcomes among patients with asthma, COPD, and no airway disease.

Methods: A retrospective cohort study was conducted on 8,395 patients admitted with COVID-19 between March 2020 and April 2021.

Comparative evaluation of glomerular morphometric techniques reveals differential technical artifacts between focal segmental glomerulosclerosis and normal glomeruli.

Morphometric estimates of mean or individual glomerular volume (MGV, IGV) have biological implications, over and above qualitative histologic data. However, morphometry is time-consuming and requires expertise limiting its utility in clinical cases. We evaluated MGV and IGV using plastic- and paraffin-embedded tissue from 10 control and 10 focal segmental glomerulosclerosis (FSGS) mice (aging and 5/6th nephrectomy models) using the gold standard Cavalieri (Cav) method versus the 2-profile and Weibel-Gomez (WG) methods and a novel 3-profile method.

Identification and validation of urinary CXCL9 as a biomarker for diagnosis of acute interstitial nephritis.

BackgroundAcute tubulointerstitial nephritis (AIN) is one of the few causes of acute kidney injury with diagnosis-specific treatment options. However, due to the need to obtain a kidney biopsy for histological confirmation, AIN diagnosis can be delayed, missed, or incorrectly assumed. Here, we identify and validate urinary CXCL9, an IFN-γ-induced chemokine involved in lymphocyte chemotaxis, as a diagnostic biomarker for AIN.

Genome-wide Association Study for AKI.

Key Points: Two genetic variants in the DISP1-TLR5 gene locus were associated with risk of AKI. DISP1 and TLR5 were differentially regulated in kidney biopsy tissue from patients with AKI compared with no AKI.

Background: Although common genetic risks for CKD are well established, genetic factors influencing risk for AKI in hospitalized patients are poorly understood.

Evaluation of Plasma Biomarkers to Predict Major Adverse Kidney Events in Hospitalized Patients With COVID-19.

Rationale & Objective: Patients hospitalized with COVID-19 are at increased risk for major adverse kidney events (MAKE). We sought to identify plasma biomarkers predictive of MAKE in patients hospitalized with COVID-19.

Study Design: Prospective cohort study.