Patterns of belatacept use and risk of post-transplant lymphoproliferative disorder in US kidney transplant recipients: An analysis of the Organ Procurement and Transplantation Network database.

Background: Belatacept is approved for the prophylaxis of organ rejection in Epstein-Barr virus (EBV)-seropositive kidney transplant recipients and is associated with a risk of post-transplant lymphoproliferative disorder (PTLD).

Methods: Data from the Organ Procurement and Transplantation Network were used to examine patterns of belatacept use, describe patient characteristics, and estimate risk of PTLD in EBV-seropositive, kidney-only transplant recipients receiving belatacept- or calcineurin inhibitor (CNI)-based immunosuppression as part of US Food and Drug Administration-mandated safety monitoring.

Results: During the study period (June 15, 2011-June 14, 2016), 94.

Enhanced Costimulation Blockade With αCD154, αCD2, and αCD28 to Promote Heart Allograft Tolerance in Nonhuman Primates.

Background: Long-term renal allograft acceptance has been achieved in macaques using a transient mixed hematopoetic chimerism protocol, but similar regimens have proven unsuccessful in heart allograft recipients unless a kidney transplant was performed simultaneously. Here, we test whether a modified protocol based on targeting CD154, CD2, and CD28 is sufficient to prolong heart allograft acceptance or promote the expansion of regulatory T cells.

Methods: Eight macaques underwent heterotopic allo-heart transplantation from major histocompatibility complex-mismatched donors.

Heart failure outcomes captured by adverse event reporting in participants with type 2 diabetes and atherosclerotic cardiovascular disease: Observations from the VERTIS CV trial.

Aims: In VERTIS CV, ertugliflozin was associated with a 30% risk reduction for adjudication-confirmed, first and total hospitalizations for heart failure (HHF) in participants with type 2 diabetes and atherosclerotic cardiovascular disease. We evaluated the impact of ertugliflozin on the broader spectrum of all reported heart failure (HF) events independent of adjudication confirmation.

Methods And Results: Data from participants who received ertugliflozin (5 or 15 mg) were pooled and compared versus placebo.

A Consistent Lack of Consistency: Definitions, Evidentiary Expectations and Potential Use of Meaningful Change Data in Clinical Outcome Assessments Across Stakeholders. Results from a DIA Working Group Literature Review and Survey.

Background: Clinical outcome assessments (COAs) measure how patients feel or function and can be used to understand which patients experience benefits of treatment and which do not. Interpretation of COA data is influenced by how meaningful change is defined. We aimed to compare how different stakeholders define, assess, and use meaningful change for decisions that impact patients.

Sacubitril/valsartan versus valsartan initiation in patients naïve to renin-angiotensin system inhibitors: Insights from PARAGLIDE-HF.

Aims: Whether prior treatment with angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) modifies efficacy and safety of sacubitril/valsartan (Sac/Val) in patients with heart failure (HF) and ejection fraction (EF) >40% is unclear, thus Sac/Val according to ACEi/ARB status at baseline was assessed.

Methods And Results: This was a pre-specified analysis of Prospective comparison of ARNI with ARB Given following stabiLization In DEcompensated HFpEF (PARAGLIDE-HF), a double-blind, randomized controlled trial of Sac/Val versus valsartan, categorizing patients according to baseline ACEi/ARB status. The primary endpoint was time-averaged proportional change in N-terminal pro-B-type natriuretic peptide (NT-proBNP) from baseline through weeks 4 and 8.

Supplemental Operational Guidance for Minimizing Potential Inhalation Doses to Workers and Volunteers at Community Reception Centers and Public Shelters.

In the event of a nuclear explosion in an urban environment, contaminated persons may be directed to Community Reception Centers (CRC) and/or public shelters. This paper is a companion document to a previous paper that addresses the inhalation hazard to workers at a CRC from resuspension of fallout from the evacuees. To limit the inhalation hazard evacuees must be screened to prevent severely contaminated persons from entering a CRC.

Optimizing Variables for Contingency Management Among Infant Caregivers Using a Simulated Purchase Task.

Behavioral economics offers a framework for understanding choice making around public health concerns such as drug use and distracted driving. Such a framework could be beneficial to understanding caregiver choices related to arranging an infant sleep environment. Nonadherence to infant sleep safety guidelines provided by the American Academy of Pediatrics increases the risk of sleep-related infant deaths.

Health Care Resource Use and Costs of Rivaroxaban Versus Warfarin Among Nonvalvular Atrial Fibrillation Polypharmacy Patients With Obesity.

Background: The economic burden of nonvalvular atrial fibrillation (NVAF) is substantial. Many patients with NVAF are obese and manage other health conditions requiring multiple medications. This real-world study compared health care resource use (HRU) and costs for rivaroxaban and warfarin in patients with NVAF who had polypharmacy and obesity.

Epistaxis Versus Nonepistaxis Bleeding in Anticoagulated Patients With Atrial Fibrillation: Results From the ENGAGE AF-TIMI 48 Trial.

Background: Epistaxis is common with antithrombotic therapy and is often troublesome to patients, yet its frequency, severity, and outcomes are poorly characterized.

Methods And Results: Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) randomized 21 105 patients with atrial fibrillation and CHADS2 risk score ≥2 to higher-dose edoxaban regimen (60 mg daily, dose-reduced to 30 mg), lower-dose edoxaban regimen (30 mg, dose reduced to 15 mg, daily), or warfarin. Bleeds were adjudicated using International Society on Thrombosis and Haemostasis criteria.

Gender-Inclusive Language in Public-Facing Labor and Delivery Web Pages in the New York Tristate Area: Cross-Sectional Study.

Background: Transgender and nonbinary (TGNB) individuals are increasingly intentionally becoming pregnant to raise children, and hospital websites should reflect these trends. For prospective TGNB parents, a hospital website is the only way they can assess their safety from discrimination while receiving perinatal care. Cisnormativity enforced by communication gaps between medical institutions and TGNB patients can and has caused delays in receiving urgent care during their pregnancy.

Chemical characterization of polymer and chloride content in waste plastic materials using pyrolysis - direct analysis in real time - high-resolution mass spectrometry.

The increasing global demand for plastic has raised the need for effective waste plastic management due to its long lifetime and resistance to environmental degradation. There is a need for rapid plastic identification to improve the mechanical waste plastic sorting process. This study presents a novel application of Temperature-Programmed Desorption-Direct Analysis in Real Time-High Resolution Mass Spectrometry (TPD-DART-HRMS) that enables rapid characterization of various plastics.

Risk for Ocular Hypertension With Intravitreal Dexamethasone Implants in Black and White Patients With Diabetic Macular Edema.

To compare the effects of intravitreal (IVT) 0.7 mg dexamethasone implants on the intraocular pressure (IOP) in Black patients and White patients with diabetic macular edema (DME). A retrospective cohort study was performed of Black patients and White patients with DME who received dexamethasone implants with 12 or more months of follow-up.

Algorithm-informed treatment from EEG patterns improves outcomes for patients with major depressive disorder.

Objective: Selecting the right medication for major depressive disorder (MDD) is challenging, and patients are often on several medications before an effective one is found. Using patient EEG patterns with computer models to select medications is a potential solution, however, it is not widely performed. Therefore, we evaluated a commercially available EEG data analysis system to help guide medication selection in a clinical setting.

Investigating the Effects of Nosocomial Infection Among Acute Leukemia Patients: Insights From the 2020 National Inpatient Sample.

Background: Rising nosocomial infections pose high risks, especially for immunocompromised leukemia patients, necessitating targeted research to enhance patient care and outcomes.The objective of this study was to investigate the impact of nosocomial infections (CDI) on patients hospitalized with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).

Methods: Our study was a retrospective analysis of adult patients hospitalized with a primary diagnosis of ALL or AML, using the Nationwide Inpatient Sample (NIS) database for 2020.

Population Pharmacokinetic Modeling of Certepetide in Human Subjects With Metastatic Pancreatic Ductal Adenocarcinoma.

Certepetide (aka LSTA1 and CEND-1) is a novel cyclic tumor-targeting internalizing arginyl glycylaspartic acid peptide being developed to treat solid tumors. Certepetide is designed to overcome existing challenges in treating solid tumors by delivering co-administered anticancer drugs into the tumor while selectively depleting immunosuppressive T cells, enhancing cytotoxic T cells in the tumor microenvironment, and inhibiting the metastatic cascade. A population pharmacokinetic (PK) analysis was conducted to characterize the concentration-time profile of patients with metastatic exocrine pancreatic cancer receiving certepetide in combination with nab-paclitaxel and gemcitabine, and to investigate the effects of clinically relevant covariates on PK parameters.

Objective study validity diagnostics: a framework requiring pre-specified, empirical verification to increase trust in the reliability of real-world evidence.

Objective: Propose a framework to empirically evaluate and report validity of findings from observational studies using pre-specified objective diagnostics, increasing trust in real-world evidence (RWE).

Materials And Methods: The framework employs objective diagnostic measures to assess the appropriateness of study designs, analytic assumptions, and threats to validity in generating reliable evidence addressing causal questions. Diagnostic evaluations should be interpreted before the unblinding of study results or, alternatively, only unblind results from analyses that pass pre-specified thresholds.

Interpretable identification of cancer genes across biological networks via transformer-powered graph representation learning.

Graph representation learning has been leveraged to identify cancer genes from biological networks. However, its applicability is limited by insufficient interpretability and generalizability under integrative network analysis. Here we report the development of an interpretable and generalizable transformer-based model that accurately predicts cancer genes by leveraging graph representation learning and the integration of multi-omics data with the topologies of homogeneous and heterogeneous networks of biological interactions.

Antimicrobial activity of imipenem/relebactam and comparator agents against Gram-negative isolates collected from pediatric patients: SMART 2018-2022 Global Surveillance.

Objectives: To evaluate the in vitro susceptibility of recent Gram-negative pathogens collected from pediatric patients to imipenem/relebactam (IMI/REL) and comparator agents.

Methods: From 2018 to 2022, 254 hospitals in 62 countries collected Enterobacterales or P. aeruginosa isolates from patients <18 years old as part of the SMART global surveillance program.

Standardized patient profile review using large language models for case adjudication in observational research.

Using administrative claims and electronic health records for observational studies is common but challenging due to data limitations. Researchers rely on phenotype algorithms, requiring labor-intensive chart reviews for validation. This study investigates whether case adjudication using the previously introduced Knowledge-Enhanced Electronic Profile Review (KEEPER) system with large language models (LLMs) is feasible and could serve as a viable alternative to manual chart review.

Prospective validation of ORACLE, a clonal expression biomarker associated with survival of patients with lung adenocarcinoma.

Human tumors are diverse in their natural history and response to treatment, which in part results from genetic and transcriptomic heterogeneity. In clinical practice, single-site needle biopsies are used to sample this diversity, but cancer biomarkers may be confounded by spatiogenomic heterogeneity within individual tumors. Here we investigate clonally expressed genes as a solution to the sampling bias problem by analyzing multiregion whole-exome and RNA sequencing data for 450 tumor regions from 184 patients with lung adenocarcinoma in the TRACERx study.