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.

Genome-wide association study of varenicline-aided smoking cessation.

Introduction: Varenicline is an α4β2 nicotinic acetylcholine receptor partial agonist with the highest therapeutic efficacy of any pharmacological smoking cessation aid and a 12-month cessation rate of 26%. Genetic variation may be associated with varenicline response, but to date no genome-wide association studies of varenicline response have been published.

Methods: In this study, we investigated the genetic contribution to varenicline effectiveness using two electronic health record-derived phenotypes.

Use of and Steering to Pharmacies Owned by Insurers and Pharmacy Benefit Managers in Medicare.

Importance: The prevalence of pharmacies owned by integrated insurers and pharmacy benefit managers (PBMs), or insurer-PBMs, is of growing regulatory concern. However, little is known about the role of these pharmacies in Medicare, in which pharmacy network protections may influence market dynamics.

Objective: To evaluate the prevalence of insurer-PBM-owned pharmacies and the extent to which insurer-PBMs steer patients to pharmacies they own in Medicare.

Repurposing Licensed Drugs with Activity Against Epstein-Barr Virus for Treatment of Multiple Sclerosis: A Systematic Approach.

Background: Epstein-Barr virus (EBV) is implicated as a necessary factor in the development of multiple sclerosis (MS) and may also be a driver of disease activity. Although it is not clear whether ongoing viral replication is the driver for MS pathology, MS researchers have considered the prospect of using drugs with potential efficacy against EBV in the treatment of MS. We have undertaken scientific and lived experience expert panel reviews to shortlist existing licensed therapies that could be used in later-stage clinical trials in MS.

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.

Do you know your PSMA-tracer? Variability in the biodistribution of different PSMA ligands and its potential impact on defining PSMA-positivity prior to PSMA-targeted therapy.

Background: In clinical practice, several radiopharmaceuticals are used for PSMA-PET imaging, each with distinct biodistribution patterns. This may impact treatment decisions and outcomes, as eligibility for PSMA-directed radioligand therapy is usually assessed by comparing tumoral uptake to normal liver uptake as a reference. In this study, we aimed to compare tracer uptake intraindividually in various reference regions including liver, parotid gland and spleen as well as the respective tumor-to-background ratios (TBR) of different F-labeled PSMA ligands to today's standard radiopharmaceutical Ga-PSMA-11 in a series of patients with biochemical recurrence of prostate cancer who underwent a dual PSMA-PET examination as part of an individualized diagnostic approach.

"It's more than a ride" veteran perceptions of peer specialist qualities and activities that were most valuable for post-incarceration reentry: a qualitative analysis.

Background: Reentry veterans experience many barriers to achieving physical and psychological well-being. While peer specialists can provide important support to veterans as they readjust to life post-incarceration, their specific activities and qualities most valued by veterans are not well known. The Post-Incarceration Engagement (PIE) intervention, coordinated with VA's Health Care for Reentry Veterans (HCRV) program, links reentry veterans with a peer specialist who provides connection to services and social-emotional support during the reentry process.

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.

Histological staining of tick bite skin biopsies for spirochetes and Powassan virus RNA.

is a vector of several human pathogens in the United States, including the cause of Lyme disease, and Powassan virus (POWV), an emerging cause of severe encephalitis. Skin biopsies from tick bite sites are frequently collected and tested for the presence of spirochetes ( spp.), which remain elusive.

Windows in the ICU and Postoperative Delirium: A Retrospective Cohort Study.

Objectives: The ICU built environment-including the presence of windows-has long been thought to play a role in delirium. This study investigated the association between the presence or absence of windows in patient rooms and ICU delirium.

Design: Retrospective single institution cohort study.

State-Level Helmet Use Laws, Helmet Use, and Head Injuries in EMS Patients Involved in Motorcycle Collisions.

Objectives: Motorcycle helmets save lives and reduce serious injury after motorcycle collisions (MCC). In 2022, 18 states had laws requiring helmet use by motorcyclists aged ≥21 years. Our objective was to compare helmet use and head trauma in emergency medical services (EMS) patients involved in MCC in states with and without helmet use laws.

Carotid artery atherosclerosis: mechanisms of instability and clinical implications.

Cardiovascular disease remains a prominent cause of disability and premature death worldwide. Within this spectrum, carotid artery atherosclerosis is a complex and multifaceted condition, and a prominent precursor of acute ischaemic stroke and other cardiovascular events. The intricate interplay among inflammation, oxidative stress, endothelial dysfunction, lipid metabolism, and immune responses participates in the development of lesions, leading to luminal stenosis and potential plaque instability.

Impact of Baseline Thrombocytopenia on Early Outcomes in Patients With Acute Venous Thromboembolism.

Managing acute venous thromboembolism (VTE) in patients with thrombocytopenia is challenging. We used data from the RIETE registry to investigate the impact of baseline thrombocytopenia on early VTE-related outcomes, depending on the initial presentation as pulmonary embolism (PE) or isolated lower-limb deep vein thrombosis (DVT). From March 2003 to November 2022, 90 418 patients with VTE were included.

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.

Contemporary Administrative Codes to Identify Pulmonary Vein Isolation Procedures for Atrial Fibrillation.

Background: Use of pulmonary vein isolation (PVI) to treat atrial fibrillation continues to increase. Despite great interest in leveraging administrative data for real-world analyses, contemporary procedural codes for identifying PVI have not been evaluated.

Methods And Results: In this observational retrospective cohort study, inpatient PVIs were identified among US Medicare fee-for-service beneficiaries using Current Procedural Terminology (CPT) code 93656 in Carrier Line Files.

The Association of TSLP and IL-4 with Patient-Reported Outcome Measures in Chronic Rhinosinusitis with Nasal Polyps.

Background: Thymic stromal lymphopoietin (TSLP) plays an important role in mediating the type-2-inflammatory response. This study examined how TSLP and interleukin (IL)-4 levels in patients with chronic rhinosinusitis with nasal polyps (CRSwNP) correlated with clinical and postoperative outcomes.

Methods: Solid-phase sandwich ELISA was used to analyze TSLP and IL-4 levels in mucus (n = 47), plasma (n = 17), polyp (n = 30), inferior (n = 25), and middle (n = 26) turbinate tissue collected during functional endoscopic sinus surgery (FESS) in CRSwNP patients (n = 76) and controls (n = 11).

Extending the translational science benefits model to implementation science for cancer prevention and control.

Introduction: There is increasing pressure on the federal research budget and shifting public opinions about the value of the academic enterprise. We must develop and apply metrics that demonstrate the broad benefits of research for health and society. The Translational Science Benefits Model (TSBM) measures the impact of large-scale translational science initiatives, such as the National Cancer Institute's Cancer Moonshot.

Magnetic Ball Chain Robots for Cardiac Arrhythmia Treatment.

This paper introduces a novel magnetic navigation system for cardiac ablation. The system is formed from two key elements: a magnetic ablation catheter consisting of a chain of spherical permanent magnets; and an actuation system comprised of two cart-mounted permanent magnets undergoing pure rotation. The catheter design enables a large magnetic content with the goal of minimizing the footprint of the actuation system for easier integration with the clinical workflow.

Adult Plastic Bronchitis: A Rare Cause for Chronic Productive Cough.

Plastic bronchitis is a rare disease with serious morbidity. We report a case of a 48-year-old male smoker with a past medical history of diabetes, emphysema, recurrent respiratory infections, a worsening productive cough, and increased oxygen requirement over the past 3 months. Often described in the pediatric population, it is important to maintain plastic bronchitis in the differential when considering unresolving pulmonary conditions with chronic sputum production.

Concomitant Tricuspid Valve Surgery With Mitral Valve Surgery for Moderate Tricuspid Regurgitation.

Background: Tricuspid valve surgical procedures (TVS) concomitant with mitral valve (MV) surgical procedures for less than severe tricuspid regurgitation (TR) remains controversial. This study examined the long-term outcomes of patients with moderate or mild to moderate TR undergoing MV surgical procedures with or without TVS.

Methods: Patients with moderate or mild to moderate TR undergoing MV replacement or repair between January 2002 and June 2021 were included.

Risk of Incident Cancer in Veterans with Diabetes Who Use Metformin Versus Sulfonylureas.

Prior research suggests metformin has anti-cancer effects, yet data are limited. We examined the association between diabetes treatment (metformin versus sulfonylurea) and risk of incident diabetes-related and non- diabetes-related cancers in US veterans. This retrospective cohort study included US veterans, without cancer, aged ≥ 55 years, who were new users of metformin or sulfonylureas for diabetes between 2001 to 2012.

Evolving trends in novel sleep tracking and sleep testing technology publications between 2020-2022.

Study Objectives: To update sleep medicine providers regarding (1) published research on the uses and performance of novel sleep tracking and testing technologies (2) the use of artificial intelligence to acquire and process sleep data and (3) research trends and gaps regarding the development and/or evaluation of these technologies.

Methods: Medline and Embase electronic databases were searched for studies utilizing screening and diagnostic sleep technologies, published between 2020 and 2022 in journals focusing on human sleep. Studies' quality was determined based on the Study Design criteria of The Oxford Centre for Evidence-Based Medicine Levels of Evidence.