Application of Evidence into Practice in Trauma: The Purpose to Practice (P2P) Approach to Consensus Generation.

Introduction: In trauma care, there is a need to increase communication to ensure evidence-informed, best practice care guidelines are easily accessible to all providers to yield continuity of care. Clinical guidance use is one way to address this need while employing a patient-centered team approach.

Methods: During year two of the conference series, participants gathered in person and virtually to further develop the Minimum Viable Product (MVP) created during year one.

Novel Pathological Mechanisms Revealed by Spatial Transcriptomic Analysis of Hippocampus in Aged Control, Primary Age-Related Tauopathy, and Alzheimer's Disease.

While both Primary Age-Related Tauopathy (PART) and Alzheimer's Disease (AD) involve the accumulation of hyperphosphorylated tau (pTau)-positive neurofibrillary tangles (NFTs) in the hippocampus, PART is distinguished by the absence of β-amyloid (Aβ) deposition and is generally associated with milder cognitive impairment than AD. To delineate cellular and molecular mechanisms that are common or uniquely linked to disease progression in PART and AD, we constructed a transcriptome-wide, high-resolution atlas of the human hippocampus using samples from six individuals spanning the aged control (AC), PART, and AD groups. Our results supported that PART represent a precursor stage of AD, as evidenced by the altered transcriptional profiles of excitatory neurons (Exc) in the PART group, which exhibited a markedly increased capacity to promote Aβ production compared to both AC and AD groups.

Epicardial adipose tissue, functional status and invasive hemodynamics in heart failure with preserved ejection fraction.

Background: EAT may play a role in the pathophysiology of HFpEF.

Objectives: This study examined associations between increased epicardial adipose tissue (EAT), functional status and invasive exercise hemodynamics in a large cohort of heart failure (HF) with preserved ejection fraction (HFpEF) patients.

Methods: All patients underwent echocardiography, 6-minute walk distance (MWD) test, Kansas City Cardiomyopathy Questionnaire (KCCQ) and invasive hemodynamic assessment at rest and during ergometry.

Coxsackievirus B infection invokes unique cell-type-specific responses in primary human pancreatic islets.

Coxsackievirus B (CVB) is implicated as an environmental trigger for type 1 diabetes (T1D). While CVB impairs islet function and viability, its impact on individual primary human islet cell types remains unclear. Here, we use single-cell RNA sequencing and functional studies to show that CVB3 induces distinct cell-type-specific transcriptional and mitochondrial responses in human cadaveric islets.

Healthcare Disparities in Spine Oncology: A Systematic Review.

Background: Metastatic spine tumors are the most common site of skeletal metastasis, leading to substantial morbidity from pain, fractures, and spinal cord compression. Despite advancements in surgical techniques and multidisciplinary care, disparities in treatment access and outcomes remain. This systematic review synthesizes the literature on disparities in surgical management of metastatic spine tumors.

Predictors of Decannulation Success in Tracheostomy: A 10-Year Analysis of the Global Tracheostomy Collaborative Database.

Objective: Decannulation is a critical milestone in functional recovery after tracheostomy, but standardized guidelines are lacking. This study examined factors associated with tracheostomy decannulation success, comparing hospital utilization, adverse events, and survival outcomes between decannulated and non-decannulated patients.

Study Design: Retrospective, observational study.

Reducing Routine Cardiology Evaluation Prior to Initiating Propranolol for Infantile Hemangiomas.

Objective: Determine if all patients with infantile hemangioma (IH) should undergo cardiology evaluation prior to initiating propranolol therapy or if only select patients should undergo cardiology evaluation, as indicated by a Propranolol Screening Checklist (PSC).

Methods: Retrospective review of 806 IH patients treated with propranolol between 2008 and 2018 at a single tertiary center. Statistical process control methods were used to compare the cardiology recommendations between the pre-PSC and post-PSC populations and there was special cause variation after implementation of the checklist.

Reactive Oxygen Species-Responsive Polymeric Chloroquine Nanogel for Targeted Oral Therapy of Ulcerative Colitis.

Targeted drug delivery remains a critical challenge in the treatment of ulcerative colitis, as the side effects of current systemic therapies often outweigh their therapeutic benefits. In this study, we developed a reactive oxygen species (ROS)-responsive nanogel system that releases polymeric chloroquine (PCQ), a macromolecular derivative of hydroxychloroquine (HCQ), for localized treatment of ulcerative colitis. The initial nanogel formulation, measuring 183 nm in size with a surface charge of +13 mV, was synthesized via RAFT polymerization using a thioketal dimethacrylate cross-linker to demonstrate ROS-triggered degradation, physicochemical stability in simulated gastrointestinal fluids, favorable biocompatibility, and preferential accumulation in inflamed colonic tissue.

Association of Patient Comorbidities with Treatment Regret Among Patients with Localized Prostate Cancer - Results from a Population-Based Cohort.

Objectives: Decision regret is a well-established, negative outcome in prostate cancer. We hypothesized that baseline comorbidities, which impact treatment tolerability, are associated with regret.

Materials And Methods: In a prospective, population-based cohort of prostate cancer patients, patient-reported regret was assessed at 12 months after treatment using a validated measure.

Amyloid-specific medication in transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis of cardiovascular outcome trials.

Background: Introduction of disease-specific medication has revolutionized the management of transthyretin associated cardiomyopathy (ATTR-CM). However, dedicated trials included different patient populations, primary endpoints, and follow-up periods, rendering study comparison challenging. This systematic review and meta-analysis aimed to harmonize data from all phase-3 placebo-controlled drug trials in ATTR-CM to inform on the magnitude and timing of treatment efficacy of ATTR-specific medication.

Subcortical brain volume variations in autistic individuals across the lifespan.

Background: Structural alterations in subcortical brain regions-including the amygdala, hippocampus, basal ganglia, and cerebral ventricles-have been linked to various clinical features of autism spectrum disorder (ASD). However, volumetric features among these regions in autistic individuals across the lifespan remain poorly understood. This cross-sectional study aimed to investigate age-associated volumetric deviations in these clinically implicated subcortical regions of autistic individuals and neurotypical controls, and to examine the structural interrelationships within each group.

Provocative testing in community dwelling older adults: a path to identify physical resilience.

Background: Resilience is the capacity of an organism to both resist and recover from stressors, and its decline can be an early indicator of susceptibility that precedes frailty, disability, and death. This study explores the use of provocative tests-time-based responses to non-harmful challenges-as potential indicators of resilience.

Methods: Provocative tests were performed in 50 community-dwelling adults (24 men, 26 women), aged 23-82 years and included cognitive challenges, strength and heart rate recovery after exercise, cold exposure, blood occlusion, and resistance to balance perturbations.

Mavacamten in Symptomatic Nonobstructive Hypertrophic Cardiomyopathy.

Background: Mavacamten is approved to treat adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM). However, its effects in nonobstructive HCM remain uncertain.

Methods: We conducted a phase 3, international, double-blind, placebo-controlled, clinical trial to determine whether mavacamten improves functional capacity and patient-reported health status among adults with symptomatic nonobstructive HCM.

Aficamten or Metoprolol Monotherapy for Obstructive Hypertrophic Cardiomyopathy.

Background: Beta-blockers have been the initial treatment for symptomatic obstructive hypertrophic cardiomyopathy (HCM) despite limited evidence of their efficacy. Aficamten is a cardiac myosin inhibitor that reduces left ventricular outflow tract gradients, improves exercise capacity, and decreases HCM symptoms when added to standard medications. Whether aficamten as monotherapy provides greater clinical benefit than beta-blockers as monotherapy remains unknown.

Accelerometry-defined physical activity and quality of life in hypertrophic cardiomyopathy.

Background: Patients with hypertrophic cardiomyopathy (HCM) often reduce their physical activity due to concerns about sudden cardiac death. However, objective data on activity patterns in HCM, particularly in relation to clinical phenotype and quality of life (QoL), remain limited.

Methods: We assessed physical activity using 7-day accelerometry in 203 patients with HCM and 37 genotype-positive, phenotype-negative (G+/P-) individuals.

Controlling intraoperative hyperglycemia in the cardiac surgical patient using the computerized electronic insulin dose calculator.

Perioperative hyperglycemia is associated with increased morbidity and mortality. We report the findings of our quality improvement project on the use of an electronic insulin dosing calculator (EIC) to reduce intraoperative hyperglycemia in a cohort of cardiac surgical patients. A pilot and a modified EIC were sequentially implemented in adult patients undergoing cardiopulmonary bypass (CPB) procedures.

A Comparison of Novel Serum Markers of Liver Health in Adolescents With Metabolic Dysfunction-Associated Steatotic Liver Disease.

Several non-invasive biomarkers for paediatric metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported, but no prior studies directly compared multiple protein or microRNA (miRNA) markers of liver health in adolescents with and without MASLD and determined which serum markers are associated with liver histopathological features. We measured 6 serum protein and 4 miRNA candidates in 3 groups of participants: 23 with obesity and biopsy-proven MASLD, 24 controls with obesity (Ob) and 24 controls with normal weight (NW). The MASLD group had higher median values for cytokeratin 18 (CK-18, 8.

Targeted Whole Genome Sequencing of African Swine Fever Virus and Classical Swine Fever Virus on the MinION Portable Sequencing Platform.

African swine fever virus (ASFV) and classical swine fever virus (CSFV) are important transboundary animal diseases (TADs) affecting swine. ASFV is a large DNA virus with a genome size of 170-190+ kilobases (kB) belonging to the family , genus Asfivirus. CSFV is a single-stranded RNA virus with a genome size of approximately 12 kB, belonging to the family , genus Pestivirus.

Refining signal localization: a transcranial magnetic stimulation motor mapping approach to functional near-infrared spectroscopy.

Functional near-infrared spectroscopy (fNIRS) has emerged as a promising brain imaging tool due to its cost-effectiveness and balance between spatial and temporal resolution. However, its reliance on the 10-20 EEG coordinate system for probe placement introduces potential inaccuracies in cortical localization. Despite concerns regarding its spatial precision, the integration of transcranial magnetic stimulation (TMS) with fNIRS for validating signal localization has not been systematically explored.

Nonsteroidal and Steroidal Mineralocorticoid Antagonists: Rationale, Evidence, and Unanswered Questions.

Steroidal mineralocorticoid receptor antagonists (MRAs), such as spironolactone and eplerenone, have demonstrated substantial benefits in randomized controlled trials for patients with heart failure with reduced ejection fraction. However, their effectiveness in heart failure with mildly reduced ejection fraction and heart failure with preserved ejection fraction remains uncertain, and the implementation of this class has remained low, in part due to its side effects and tolerability profile. Emerging therapies that target the mineralocorticoid receptor and/or the production of aldosterone may offer alternative strategies to treat the aldosterone-mineralocorticoid receptor axis.

Optimizing Selection of Bridging Therapies Prior to CAR-T Therapy Administration for Multiple Myeloma: Clinical Pearls From an Expert Roundtable.

Autologous chimeric antigen receptor T-cell (CAR-T) therapies have become a key component of the multiple myeloma (MM) treatment landscape. Most patients treated with CAR-T therapies for MM receive bridging therapy to reduce tumor burden prior to CAR-T administration. These treatments are highly individualized, with selection informed by disease characteristics and treatment history, among other factors.

How menopause symptoms shape experiences of the criminal legal system: A qualitative study across the United States.

Introduction: The number of midlife individuals involved in the criminal legal system has increased significantly in recent decades. Despite this growth, little is known about the ways in which experiences of midlife, including the menopause transition, shape experiences within the criminal legal system. This study explores the intersection between people's experiences of menopause and experiences of the criminal legal system.

BREEZE Optional Extension Phase: Long-term safety and efficacy of treprostinil dry powder inhaler (Tyvaso DPI) in pulmonary arterial hypertension.

Introduction: Pulmonary arterial hypertension (PAH) is a rare and progressive disease associated with significant morbidity and mortality. Prostacyclins, including treprostinil, are a mainstay of PAH treatment, particularly in patients with intermediate to high risk of death. Following the approval of treprostinil inhalation solution for PAH, treprostinil dry powder inhaler (DPI) was developed as a small, portable, low-maintenance device to improve patient experience.

From dark horse to front-runner: vascular contributions to brain health : Proceedings of the 2022 annual workshop of the Albert research institute for white matter and cognition.

It is becoming increasingly clear that the cerebral microcirculation plays a central role in the development and progression of Alzheimer's Disease and Alzheimer's Disease-Related Dementias (AD/ADRD). Despite recent advances in understanding the vascular contributions to cognitive impairment and decline, many gaps exist in our collective knowledge. The 2022 Annual Workshop of the Albert Research Institute for White Matter and Cognition brought together investigators in the fields of neurovascular function and health, blood-brain barrier integrity, neurodegeneration, cerebral microvascular function, brain imaging, integrative systems neuroscience, and clinicians to discuss exciting and novel findings on how the vasculature contributes to progression of dementia.