Immunologic investigations into transgene directed immune-mediated myositis following delandistrogene moxeparvovec gene therapy.

Delandistrogene moxeparvovec is an rAAVrh74 vector-based gene transfer therapy that delivers a transgene encoding delandistrogene moxeparvovec micro-dystrophin, an engineered, functional form of dystrophin shown to stabilize or slow disease progression in DMD. It is approved in the US and in other select countries. Two serious adverse event cases of immune-mediated myositis (IMM) were reported in the phase Ib ENDEAVOR trial (NCT04626674).

The impact of margins and re-resection in pediatric synovial sarcoma.

Introduction: Synovial sarcoma is one of the most common soft tissue sarcomas in children. Guidelines regarding the adequate extent of resection margins and the role of re-resection are lacking. We sought to evaluate the adequate resection margin and the role of re-resection in predicting outcomes in children with synovial sarcomas.

Impact of Elevated Serum Triglycerides on Children with Acute Recurrent or Chronic Pancreatitis from INSPPIRE-2.

Objective: To determine if mild-moderate hypertriglyceridemia (HTG) is associated with increased development of chronic pancreatitis (CP) or pancreatitis-associated complications in children with acute recurrent or CP.

Study Design: Longitudinal data from the INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2) cohort of children with acute recurrent or CP (n = 559) were analyzed. Subjects were divided into normal triglycerides (<150 mg/dL; 1.

External Validation of an Electronic Phenotyping Algorithm Detecting Attention to High Body Mass Index in Pediatric Primary Care.

Objectives:  The lack of feasible and meaningful measures of clinicians' behavior hinders efforts to assess and improve obesity management in pediatric primary care. In this study, we examined the external validity of a novel algorithm, previously validated in a single geographic region, using structured electronic health record (EHR) data to identify phenotypes of clinicians' attention to elevated body mass index (BMI) and weight-related comorbidities.

Methods:  We extracted structured EHR data for 300 randomly selected 6- to 12-year-old children with elevated BMI seen for well-child visits from June 2018 to May 2019 at pediatric primary care practices affiliated with Yale.

Migration, invasion, and metastasis are mediated by in neuroblastoma.

Neuroblastoma accounts for approximately 15% of pediatric cancer-related deaths despite intensive multimodal therapy. This is due, in part, to high rates of metastatic disease at diagnosis and disease relapse. A better understanding of tumor biology of aggressive, pro-metastatic phenotypes is necessary to develop novel, more effective therapeutics against neuroblastoma.

Development of an augmented reality system for tracheal intubation guidance of airway management.

Tracheal intubation is a crucial procedure performed in airway management to sustain life during various procedures. However, difficult airways can make intubation challenging, which is associated with increased mortality and morbidity. This is particularly important for children who undergo intubation where the situation is difficult.

Hospital costs and reimbursement for short-stay inpatient versus observation status hospitalizations for children with medical complexity.

Background: There is a lack of uniformity across hospitals in applying inpatient versus observation status for short-stay (<48 h) pediatric hospitalizations, with negative financial implications associated with observation. Children with medical complexity (CMC) represent a growing population and incur high costs of care. The financial implications of inpatient and observation status for CMC have not been studied.

Effect of Remimazolam on Emergence Delirium in Children Undergoing Laparoscopic Surgery: A Double-blinded Randomized Trial.

Background: Preventing emergence delirium is a clinical goal for pediatric anesthesia, yet there is no consensus on its prevention. This study investigated the hypothesis that a continuous infusion or a single bolus of remimazolam can reduce the incidence of emergence delirium in children.

Methods: A total of 120 children aged 1 to 6 yr were randomly and equally allocated into three groups: group RC, which received a continuous infusion of remimazolam at 1 mg · kg-1 · h-1; group RB, which received a single bolus of remimazolam at 0.

Lower opportunity ZIP code is associated with worse outcomes after listing in pediatric heart transplantation.

Background: The Child Opportunity Index (COI) comprehensively measures children's social determinants of health. We describe association between COI and outcomes after listing for heart transplantation.

Methods: We conducted a retrospective review of the United Network for Organ Sharing (UNOS) database for U.

Comparison of Deep and Moderate Neuromuscular Blockade for Major Laparoscopic Surgery in Children: A Randomized Controlled Trial.

Background And Objective: Neuromuscular blocking agents are routinely used in laparoscopic surgery to optimize operative conditions. We compared the effect of a deep and moderate neuromuscular blockade (NMB) on surgical conditions and postoperative outcomes in children undergoing major laparoscopic surgery.

Methods: Sixty children aged 2-14 years scheduled to undergo major laparoscopic surgery were randomly allocated to deep (post-tetanic count 1-2 twitches) or moderate (train-of-four 1-2 twitches) NMB groups.

WDR5 facilitates recruitment of N-MYC to conserved WDR5 gene targets in neuroblastoma cell lines.

Collectively, the MYC family of oncoprotein transcription factors is overexpressed in more than half of all malignancies. The ability of MYC proteins to access chromatin is fundamental to their role in promoting oncogenic gene expression programs in cancer and this function depends on MYC-cofactor interactions. One such cofactor is the chromatin regulator WDR5, which in models of Burkitt lymphoma facilitates recruitment of the c-MYC protein to chromatin at genes associated with protein synthesis, allowing for tumor progression and maintenance.

Plasticity between type 2 innate lymphoid cell subsets and amphiregulin expression regulates epithelial repair in biliary atresia.

Background And Aims: Although a dysregulated type 1 immune response is integral to the pathogenesis of biliary atresia, studies in both humans and mice have uncovered a type 2 response, primarily driven by type 2 innate lymphoid cells. In nonhepatic tissues, natural type 2 innate lymphoid cell (nILC2s) regulate epithelial proliferation and tissue repair, whereas inflammatory ILC2s (iIlC2s) drive tissue inflammation and injury. The aim of this study is to determine the mechanisms used by type 2 innate lymphoid cell (ILC2) subpopulations to regulate biliary epithelial response to an injury.

Optimal Positioning of Nasopharyngeal Temperature Probes in Infants and Children: A Prospective Cohort Study.

Background: The nasopharynx is an easily accessible core-temperature monitoring site, but insufficient or excessive nasopharyngeal probe insertion can underestimate core temperature. Our goal was to estimate optimal nasopharyngeal probe insertion depth as a function of age.

Methods: We enrolled 157 pediatric patients who had noncardiac surgery with endotracheal intubation in 5 groups: (1) newborn to 6 months old, (2) infants 7 months to 1 year old, (3) children 13 to 23 months old, (4) children 2 to 5 years old, and (5) children 6 to 12 years old.

Sixth Annual Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs) Report: The Society Of Thoracic Surgeons Pedimacs Annual Report.

Background: The Pediatric Interagency Registry for Mechanical Circulatory Support (Pedimacs), supported by The Society of Thoracic Surgeons, provides detailed information on pediatric patients supported with ventricular assist devices (VADs).

Methods: From September 19, 2012, to December 31, 2021, there were 1355 devices in 1109 patients (<19 years) from 42 North American Hospitals.

Results: Cardiomyopathy was the most common underlying cause (59%), followed by congenital heart disease (25%) and myocarditis (9%).

Combination bromo- and extraterminal domain and poly (ADP-ribose) polymerase inhibition synergistically enhances DNA damage and inhibits neuroblastoma tumorigenesis.

Purpose: JQ1 is a bromo- and extraterminal (BET) domain inhibitor that downregulates MYC expression and impairs the DNA damage response. Poly (ADP-ribose) polymerase (PARP) inhibitors prevent DNA damage sensing and repair. We hypothesized that JQ1 would promote a DNA repair-deficient phenotype that sensitizes neuroblastoma cells to PARP inhibition.

Hospital-Level Neighborhood Opportunity and Rehospitalization for Common Diagnoses at US Children's Hospitals.

Objective: Neighborhood conditions influence child health outcomes, but data examining association between local factors and hospital utilization are lacking. We determined if hospitals' mix of patients by neighborhood opportunity correlates with rehospitalization for common diagnoses at US children's hospitals.

Methods: We analyzed all discharges in 2018 for children ≤18 years at 47 children's hospitals for 14 common diagnoses.

Consensus Statement: Hemostasis Trial Outcomes in Cardiac Surgery and Mechanical Support.

Background: Research evaluating hemostatic agents for the treatment of clinically significant bleeding has been hampered by inconsistency and lack of standardized primary clinical trial outcomes. Clinical trials of hemostatic agents in both cardiac surgery and mechanical circulatory support, such as extracorporeal membrane oxygenation and ventricular assist devices, are examples of studies that lack implementation of universally accepted outcomes.

Methods: A subgroup of experts convened by the National Heart, Lung, and Blood Institute and the US Department of Defense developed consensus recommendations for primary outcomes in cardiac surgery and mechanical circulatory support.

Lifespan Perspective on Congenital Heart Disease Research: JACC State-of-the-Art Review.

More than 90% of patients with congenital heart disease (CHD) are nowadays surviving to adulthood and adults account for over two-thirds of the contemporary CHD population in Western countries. Although outcomes are improved, surgery does not cure CHD. Decades of longitudinal observational data are currently motivating a paradigm shift toward a lifespan perspective and proactive approach to CHD care.