Upgrading Right Ventricular Pacing to Cardiac Resynchronization in HFrEF Patients Improves Symptoms and Functional Outcomes.

Background: In the BUDAPEST (Biventricular Upgrade on left ventricular reverse remodeling and clinical outcomes in patients with left ventricular Dysfunction and intermittent or permanent APical/SepTal right ventricular pacing)-CRT Upgrade randomized trial, the authors have demonstrated improved mortality and morbidity after cardiac resynchronization therapy (CRT) upgrade in patients with heart failure with reduced ejection fraction (HFrEF) with high right ventricular (RV) pacing burden.

Objectives: This substudy sought to examine the impact of CRT upgrade on symptoms, functional outcome, and exercise capacity.

Methods: In the BUDAPEST-CRT Upgrade trial, 360 HFrEF patients with pacemaker or implantable cardioverter-defibrillator (ICD) and ≥20% RV pacing burden were randomly assigned (3:2) to cardiac resynchronization therapy with defibrillator (CRT-D) upgrade (n = 215) or ICD (n = 145).

Ocular and Systemic Anomalies in an Infant With 4q Deletion and 3q Duplication: Case Report and Review of Literature.

This is a case report of a female infant with two rare pathogenic chromosomal abnormalities: partial trisomy of chromosome 3 (3q25.2 to 3q29) and partial monosomy of chromosome 4 (4q34.1 to 4q35.

Electronic Health Record Data Quality and Performance Assessments: Scoping Review.

Background: Electronic health records (EHRs) have an enormous potential to advance medical research and practice through easily accessible and interpretable EHR-derived databases. Attainability of this potential is limited by issues with data quality (DQ) and performance assessment.

Objective: This review aims to streamline the current best practices on EHR DQ and performance assessments as a replicable standard for researchers in the field.

Risk-Specific Training Cohorts to Address Class Imbalance in Surgical Risk Prediction.

Importance: Machine learning tools are increasingly deployed for risk prediction and clinical decision support in surgery. Class imbalance adversely impacts predictive performance, especially for low-incidence complications.

Objective: To evaluate risk-prediction model performance when trained on risk-specific cohorts.

Community-engaged artificial intelligence research: A scoping review.

The degree to which artificial intelligence healthcare research is informed by data and stakeholders from community settings has not been previously described. As communities are the principal location of healthcare delivery, engaging them could represent an important opportunity to improve scientific quality. This scoping review systematically maps what is known and unknown about community-engaged artificial intelligence research and identifies opportunities to optimize the generalizability of these applications through involvement of community stakeholders and data throughout model development, validation, and implementation.

Non-invasive myocardial work as an independent predictor of postprocedural NT-proBNP in elderly patients undergoing transcatheter aortic valve replacement.

Aortic stenosis has become the most prevalent valvular disease with increasing life expectancy and the ageing of the population, representing a significant clinical burden for health care providers. Its treatment has been revolutionized by transcatheter aortic valve replacement (TAVR) as a safe and minimally invasive option for elderly patients. Left ventricular (LV) functional measurement is of particular importance before TAVR, however, increased afterload significantly influences the conventional echocardiographic parameters.

A Comparative Investigation of the Pulmonary Vasodilating Effects of Inhaled NO Gas Therapy and Inhalation of a New Drug Formulation Containing a NO Donor Metabolite (SIN-1A).

Numerous research projects focused on the management of acute pulmonary hypertension as Coronavirus Disease 2019 (COVID-19) might lead to hypoxia-induced pulmonary vasoconstriction related to acute respiratory distress syndrome. For that reason, inhalative therapeutic options have been the subject of several clinical trials. In this experimental study, we aimed to examine the hemodynamic impact of the inhalation of the SIN-1A formulation (N-nitroso-N-morpholino-amino-acetonitrile, the unstable active metabolite of molsidomine, stabilized by a cyclodextrin derivative) in a porcine model of acute pulmonary hypertension.

Association of Sociodemographic Factors With Overtriage, Undertriage, and Value of Care After Major Surgery.

Objective: To determine whether certain patients are vulnerable to errant triage decisions immediately after major surgery and whether there are unique sociodemographic phenotypes within overtriaged and undertriaged cohorts.

Background: In a fair system, overtriage of low-acuity patients to intensive care units (ICUs) and undertriage of high-acuity patients to general wards would affect all sociodemographic subgroups equally.

Methods: This multicenter, longitudinal cohort study of hospital admissions immediately after major surgery compared hospital mortality and value of care (risk-adjusted mortality/total costs) across 4 cohorts: overtriage (N = 660), risk-matched overtriage controls admitted to general wards (N = 3077), undertriage (N = 2335), and risk-matched undertriage controls admitted to ICUs (N = 4774).

Key influences of VDD (DX) ICD selection: Results from a prospective, national survey.

Background: To preserve the benefit of atrial sensing without the implantation of an additional lead, a single-lead ICD system with a floating atrial dipole (DX ICD) has been developed. The purpose of this nationwide survey was to provide an overview of the current key influences of device selection focusing on DX ICD and to test the applicability of a previously published decision-making flowchart of ICD-type selection.

Methods: An online questionnaire was sent to all implanting centers in Hungary.

Two new user-friendly methods to assess pharmacometric parameter identifiability on categorical and continuous scales.

Parameter identifiability methods assess whether the parameters of a model are uniquely determined by the observations. While the success of a model fit can provide some information on this, it can be valuable to determine identifiability before any fit has been attempted, or to separate identifiability from other issues. Two concepts that lean themselves well for identifiability analysis and have been underutilized are the sensitivity matrix (SM) and the Fisher information matrix (FIM).

Navigating the landscape of parameter identifiability methods: A workflow recommendation for model development.

In pharmacometric modeling, it is often important to know whether the data is sufficiently rich to identify the parameters of a proposed model. While it may be possible to assess this based on the results of a model fit, it is often difficult to disentangle identifiability issues from other model fitting and numerical problems. Furthermore, it can be of value to ascertain identifiability beforehand.

Development and validation of a race-agnostic computable phenotype for kidney health in adult hospitalized patients.

Standard race adjustments for estimating glomerular filtration rate (GFR) and reference creatinine can yield a lower acute kidney injury (AKI) and chronic kidney disease (CKD) prevalence among African American patients than non-race adjusted estimates. We developed two race-agnostic computable phenotypes that assess kidney health among 139,152 subjects admitted to the University of Florida Health between 1/2012-8/2019 by removing the race modifier from the estimated GFR and estimated creatinine formula used by the race-adjusted algorithm (race-agnostic algorithm 1) and by utilizing 2021 CKD-EPI refit without race formula (race-agnostic algorithm 2) for calculations of the estimated GFR and estimated creatinine. We compared results using these algorithms to the race-adjusted algorithm in African American patients.

NASH triggers cardiometabolic HFpEF in aging mice.

Both heart failure with preserved ejection fraction (HFpEF) and non-alcoholic fatty liver disease (NAFLD) develop due to metabolic dysregulation, has similar risk factors (e.g., insulin resistance, systemic inflammation) and are unresolved clinical challenges.

Identifying acute illness phenotypes via deep temporal interpolation and clustering network on physiologic signatures.

Using clustering analysis for early vital signs, unique patient phenotypes with distinct pathophysiological signatures and clinical outcomes may be revealed and support early clinical decision-making. Phenotyping using early vital signs has proven challenging, as vital signs are typically sampled sporadically. We proposed a novel, deep temporal interpolation and clustering network to simultaneously extract latent representations from irregularly sampled vital signs and derive phenotypes.

A multi-site study on sex differences in cortical thickness in non-demented Parkinson's disease.

Clinical, cognitive, and atrophy characteristics depending on sex have been previously reported in Parkinson's disease (PD). However, though sex differences in cortical gray matter measures in early drug naïve patients have been described, little is known about differences in cortical thickness (CTh) as the disease advances. Our multi-site sample comprised 211 non-demented PD patients (64.

Intraoperative hypotension and postoperative acute kidney injury: A systematic review.

Background: There is no consensus regarding safe intraoperative blood pressure thresholds that protect against postoperative acute kidney injury (AKI). This review aims to examine the existing literature to delineate safe intraoperative hypotension (IOH) parameters to prevent postoperative AKI.

Methods: PubMed, Cochrane Central, and Web of Science were systematically searched for articles published between 2015 and 2022 relating the effects of IOH on postoperative AKI.

Effect of pharmacological selectivity of SGLT2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes: a meta-analysis.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce major adverse cardiovascular events (MACE) in type 2 diabetic (T2DM) patients. Pharmacological selectivity of these agents to SGLT2 over SGLT1 is highly variant, with unknown clinical relevance. Genetically reduced SGLT1-but not SGLT2-activity correlates with lower risk of heart failure and mortality, therefore additional non-selective SGLT1 inhibition might be beneficial.

Pharmacokinetics and pharmacodynamics of finerenone in patients with chronic kidney disease and type 2 diabetes: Insights based on FIGARO-DKD and FIDELIO-DKD.

Aims: To perform dose-exposure-response analyses to determine the effects of finerenone doses.

Materials And Methods: Two randomized, double-blind, placebo-controlled phase 3 trials enrolling 13 026 randomized participants with type 2 diabetes (T2D) from global sites, each with an estimated glomerular filtration rate (eGFR) of 25 to 90 mL/min/1.73 m , a urine albumin-creatinine ratio (UACR) of 30 to 5000 mg/g, and serum potassium ≤ 4.

Time-resolved crystallography captures light-driven DNA repair.

Photolyase is an enzyme that uses light to catalyze DNA repair. To capture the reaction intermediates involved in the enzyme's catalytic cycle, we conducted a time-resolved crystallography experiment. We found that photolyase traps the excited state of the active cofactor, flavin adenine dinucleotide (FAD), in a highly bent geometry.

Clinical courses of acute kidney injury in hospitalized patients: a multistate analysis.

Persistence of acute kidney injury (AKI) or insufficient recovery of renal function was associated with reduced long-term survival and life quality. We quantified AKI trajectories and describe transitions through progression and recovery among hospitalized patients. 245,663 encounters from 128,271 patients admitted to UF Health between 2012 and 2019 were retrospectively categorized according to the worst AKI stage experienced within 24-h periods.

Erythrocytapheresis in Children and Young Adults with Hemoglobinopathies and Iron Overload in Need of Iron Chelation Therapy.

Limited data regarding erythrocytapheresis in children, adolescents, and young adults have been published. The aim of this study was to evaluate erythrocytapheresis, either as a standalone therapy or in combination with iron chelation therapy, in children and young adults with hemoglobinopathies in whom current iron chelation therapy is not sufficient in decreasing the iron overload during management. We retrospectively analysed erythrocytapheresis in 19 patients with hemoglobinopathies in need of iron chelation therapy diagnosed with sickle cell disease (SCD) or β-thalassemia major.

Droplet Digital PCR Is a Novel Screening Method Identifying Potential Cardiac G-Protein-Coupled Receptors as Candidate Pharmacological Targets in a Rat Model of Pressure-Overload-Induced Cardiac Dysfunction.

The identification of novel drug targets is needed to improve the outcomes of heart failure (HF). G-protein-coupled receptors (GPCRs) represent the largest family of targets for already approved drugs, thus providing an opportunity for drug repurposing. Here, we aimed (i) to investigate the differential expressions of 288 cardiac GPCRs via droplet digital PCR (ddPCR) and bulk RNA sequencing (RNAseq) in a rat model of left ventricular pressure-overload; (ii) to compare RNAseq findings with those of ddPCR; and (iii) to screen and test for novel, translatable GPCR drug targets in HF.

Pressure overload-induced systolic heart failure is associated with characteristic myocardial microRNA expression signature and post-transcriptional gene regulation in male rats.

Although systolic function characteristically shows gradual impairment in pressure overload (PO)-evoked left ventricular (LV) hypertrophy (LVH), rapid progression to congestive heart failure (HF) occurs in distinct cases. The molecular mechanisms for the differences in maladaptation are unknown. Here, we examined microRNA (miRNA) expression and miRNA-driven posttranscriptional gene regulation in the two forms of PO-induced LVH (with/without systolic HF).

Machine Learning-Enabled Clinical Information Systems Using Fast Healthcare Interoperability Resources Data Standards: Scoping Review.

Background: Machine learning-enabled clinical information systems (ML-CISs) have the potential to drive health care delivery and research. The Fast Healthcare Interoperability Resources (FHIR) data standard has been increasingly applied in developing these systems. However, methods for applying FHIR to ML-CISs are variable.