Physical Activity Correlates With Skeletal Muscle MRI Findings in Individuals With Duchenne Muscular Dystrophy.

Introduction/aims: Skeletal muscle magnetic resonance imaging (MRI) is a validated noninvasive tool to assess Duchenne muscular dystrophy (DMD) progression. There is interest in finding DMD biomarkers that decrease the burden of clinical trial participation, such as wearable devices. Our aim was to evaluate the relationship between activity, via accelerometry, and skeletal muscle MRI, particularly T mapping.

The uremic toxin indoxyl sulfate decreases osteocyte RANKL/OPG and increases Wnt inhibitor RNA expression that is reversed by PTH.

Renal osteodystrophy (ROD) leads to increased fractures, potentially due to underlying low bone turnover in chronic kidney disease (CKD). We hypothesized that indoxyl sulfate (IS), a circulating toxin elevated in CKD and a ligand for the aryl hydrocarbon receptor (AhR), may target the osteocytes leading to bone cell uncoupling in ROD. The IDG-SW3 osteocytes were cultured for 14 days (early) and 35 days (mature osteocytes) and incubated with 500 μM of IS after dose finding studies to confirm AhR activation.

The islet tissue plasminogen activator/plasmin system is upregulated with human islet amyloid polypeptide aggregation and protects beta cells from aggregation-induced toxicity.

Aims/hypothesis: Apart from its fibrinolytic activity, the tissue plasminogen activator (tPA)/plasmin system has been reported to cleave the peptide amyloid beta, attenuating brain amyloid deposition in Alzheimer's disease. As aggregation of human islet amyloid polypeptide (hIAPP) is toxic to beta cells, we sought to determine whether activation of the fibrinolytic system can also reduce islet amyloid deposition and its cytotoxic effects, which are both observed in type 2 diabetes.

Methods: The expression of Plat (encoding tPA) and plasmin activity were measured in isolated islets from amyloid-prone hIAPP transgenic mice or non-transgenic control islets expressing non-amyloidogenic mouse islet amyloid polypeptide cultured in the absence or presence of the amyloid inhibitor Congo Red.

Framework for Research Gaps in Pediatric Ventilator Liberation.

Background: The 2023 International Pediatric Ventilator Liberation Clinical Practice Guidelines provided evidence-based recommendations to guide pediatric critical care providers on how to perform daily aspects of ventilator liberation. However, because of the lack of high-quality pediatric studies, most recommendations were conditional based on very low to low certainty of evidence.

Research Question: What are the research gaps related to pediatric ventilator liberation that can be studied to strengthen the evidence for future updates of the guidelines?

Study Design And Methods: We conducted systematic reviews of the literature in eight predefined Population, Intervention, Comparator, Outcome (PICO) areas related to pediatric ventilator liberation to generate recommendations.

RISING STARS: Evidence for established and emerging forms of β-cell death.

β-Cell death contributes to β-cell loss and insulin insufficiency in type 1 diabetes (T1D), and this β-cell demise has been attributed to apoptosis and necrosis. Apoptosis has been viewed as the lone form of programmed β-cell death, and evidence indicates that β-cells also undergo necrosis, regarded as an unregulated or accidental form of cell demise. More recently, studies in non-islet cell types have identified and characterized novel forms of cell death that are biochemically and morphologically distinct from apoptosis and necrosis.

Methods for pragmatic randomized clinical trials of pain therapies: IMMPACT statement.

Pragmatic, randomized, controlled trials hold the potential to directly inform clinical decision making and health policy regarding the treatment of people experiencing pain. Pragmatic trials are designed to replicate or are embedded within routine clinical care and are increasingly valued to bridge the gap between trial research and clinical practice, especially in multidimensional conditions, such as pain and in nonpharmacological intervention research. To maximize the potential of pragmatic trials in pain research, the careful consideration of each methodological decision is required.

Use of urine neutrophil gelatinase-associated lipocalin for nephrotoxic medication acute kidney injury screening in neonates.

Background: Daily serum creatinine monitoring protocols for acute kidney injury (AKI) are invasive and may lead to surveillance resistance. We aimed to understand if use of urine neutrophil gelatinase-associated lipocalin (uNGAL) could increase high-risk nephrotoxic medication (NTMx) associated AKI screening adherence in neonates.

Methods: Statistical process control methods prior to and post implementation were trended.

Using Bibliometric Analysis to Map the Impact of a Simulation Program's Published Scholarly Works.

Bibliometrics quantitatively evaluates the targeted literature sources and can help define research and scholarly publications' impact and demonstrate connections for authors, departments, or universities. This article presents a methodology for simulation programs to evaluate their influence in terms of both impact and scope of their published simulation-based healthcare scholarly output. Using the authors' home university and healthcare system as an example, the article outlines a methodology to map research and scholarly works networks within the systems, identify and map connections outside the system, and quantifiably score the overall impact of the simulation program's scholarly output using a common scoring metric, the h-index.

Risk Factors for Meeting Criteria for Switching from Bevacizumab to Aflibercept When Treating Eyes with Diabetic Macular Edema and Visual Acuity of < 20/40.

Purpose: To identify factors for meeting prespecified criteria for switching from bevacizumab to aflibercept in eyes with center-involved diabetic macular edema (CI-DME) and moderate vision loss initially treated with bevacizumab in DRCR Retina Network protocol AC.

Design: Post hoc analysis of data from a randomized clinical trial.

Participants: Two hundred seventy participants with one or both eyes harboring CI-DME with visual acuity (VA) letter score of 69 to 24 (Snellen equivalent, 20/50-20/320).

Privacy-preserving record linkage across disparate institutions and datasets to enable a learning health system: The national COVID cohort collaborative (N3C) experience.

Introduction: Research driven by real-world clinical data is increasingly vital to enabling learning health systems, but integrating such data from across disparate health systems is challenging. As part of the NCATS National COVID Cohort Collaborative (N3C), the N3C Data Enclave was established as a centralized repository of deidentified and harmonized COVID-19 patient data from institutions across the US. However, making this data most useful for research requires linking it with information such as mortality data, images, and viral variants.

RIPK3 promotes islet amyloid-induced β-cell loss and glucose intolerance in a humanized mouse model of type 2 diabetes.

Objective: Aggregation of human islet amyloid polypeptide (hIAPP), a β-cell secretory product, leads to islet amyloid deposition, islet inflammation and β-cell loss in type 2 diabetes (T2D), but the mechanisms that underlie this process are incompletely understood. Receptor interacting protein kinase 3 (RIPK3) is a pro-death signaling molecule that has recently been implicated in amyloid-associated brain pathology and β-cell cytotoxicity. Here, we evaluated the role of RIPK3 in amyloid-induced β-cell loss using a humanized mouse model of T2D that expresses hIAPP and is prone to islet amyloid formation.

An ischemic myelopathy case series: Flaccid paraplegia following a spike ball save and numbness while walking normally.

Spinal cord infarctions in children are rare and early magnetic resonance imaging studies are often negative. A high clinical suspicion must be maintained to identify stroke and initiate workup for underlying etiology to suggest appropriate treatment. We present two cases of spinal cord infarction without major preceding trauma.

Design and Implementation of the Diabetes Impact Project: A Multisector Partnership to Reduce Diabetes Burden in Indianapolis Communities.

Context: Community-level health disparities have not arisen suddenly but are the result of long-term systemic inequities. This article describes the design and implementation of a community-engaged multisector partnership to address health disparities by reducing the diabetes burden in 3 Indianapolis communities through the implementation of evidence-based strategies across the prevention continuum.

Program: The project has 5 foundational design principles: engage partners from multiple sectors to address community health, focus on geographic communities most affected by the health disparity, practice authentic community engagement, commit for the long term, and utilize a holistic approach spanning the prevention continuum.

Provision and availability of genomic medicine services in Level IV neonatal intensive care units.

Purpose: To describe variation in genomic medicine services across level IV neonatal intensive care units (NICUs) in the United States and Canada.

Methods: We developed and distributed a novel survey to the 43 level IV NICUs belonging to the Children's Hospitals Neonatal Consortium, requesting a single response per site from a clinician with knowledge of the provision of genomic medicine services.

Results: Overall response rate was 74% (32/43).

Association of Extubation Failure Rates With High-Flow Nasal Cannula, Continuous Positive Airway Pressure, and Bilevel Positive Airway Pressure vs Conventional Oxygen Therapy in Infants and Young Children: A Systematic Review and Network Meta-Analysis.

Importance: Extubation failure (EF) has been associated with worse outcomes in critically ill children. The relative efficacy of different modes of noninvasive respiratory support (NRS) to prevent EF is unknown.

Objective: To study the reported relative efficacy of different modes of NRS (high-flow nasal cannula [HFNC], continuous positive airway pressure [CPAP], and bilevel positive airway pressure [BiPAP]) compared to conventional oxygen therapy (COT).

Design of a multi-institutional neurocognitive discovery study in adult congenital heart disease (MINDS-ACHD).

Background: Neurocognitive dysfunction (NCD) is a common comorbidity among children with congenital heart disease (CHD). However, it is unclear how underlying CHD and its sequelae combine with genetics and acquired cardiovascular and neurological disease to impact NCD and outcomes across the lifespan in adults with CHD.

Methods: The Multi-Institutional Neurocognitive Discovery Study in Adults with Congenital Heart Disease (MINDS-ACHD) is a partnership between the Pediatric Heart Network (PHN) and the Adult Alliance for Research in Congenital Cardiology (AARCC) that examines objective and subjective neurocognitive function and genetics in young ACHD.

Research objectives and general considerations for pragmatic clinical trials of pain treatments: IMMPACT statement.

Many questions regarding the clinical management of people experiencing pain and related health policy decision-making may best be answered by pragmatic controlled trials. To generate clinically relevant and widely applicable findings, such trials aim to reproduce elements of routine clinical care or are embedded within clinical workflows. In contrast with traditional efficacy trials, pragmatic trials are intended to address a broader set of external validity questions critical for stakeholders (clinicians, healthcare leaders, policymakers, insurers, and patients) in considering the adoption and use of evidence-based treatments in daily clinical care.

A Quality Improvement Initiative to Reduce Unnecessary Screening Chest Radiographs in a Pediatric ICU.

Background: The Critical Care Societies Collaborative included not ordering diagnostic tests at regular intervals as one of their Choosing Wisely initiatives. A reduction in unnecessary chest radiographs (CXRs) can help reduce exposure to radiation and eliminate health care waste. We aimed to reduce daily screening CXRs in a pediatric ICU (PICU) by 20% from baseline within 4 months of implementation of CXR criteria.