IMPACT OF ABCC8 AND TRPM4 GENETIC VARIATION IN CENTRAL NERVOUS SYSTEM DYSFUNCTION ASSOCIATED WITH PEDIATRIC SEPSIS.

Background: Sepsis-associated brain injury is associated with deterioration of mental status, persistent cognitive impairment, and morbidity. The SUR1/TRPM4 channel is a nonselective cation channel that is transcriptionally upregulated in the central nervous system with injury, allowing sodium influx, depolarization, cellular swelling, and secondary injury. We hypothesized that genetic variation in ABCC8 (SUR1 gene) and TRPM4 would associate with central nervous system dysfunction in severe pediatric sepsis.

Risk factors for prolonged infection and secondary infection in pediatric severe sepsis.

Purpose: Sepsis causes significant worldwide morbidity and mortality. Inability to clear an infection and secondary infections are known complications in severe sepsis and likely result in worsened outcomes. We sought to characterize risk factors of these complications.

Stepwise training program: A novel practice schedule for laparoscopic suturing.

Purpose: We establish stepwise training program in which laparoscopic suturing is broken down to discrete steps. The purpose is to evaluate the learning outcomes of stepwise training program.

Materials And Methods: Volunteer participants were enrolled from medical students and surgical trainees.

Hyperferritinemic sepsis, macrophage activation syndrome, and mortality in a pediatric research network: a causal inference analysis.

Background: One of five global deaths are attributable to sepsis. Hyperferritinemic sepsis (> 500 ng/mL) is associated with increased mortality in single-center studies. Our pediatric research network's objective was to obtain rationale for designing anti-inflammatory clinical trials targeting hyperferritinemic sepsis.

Mortality Risk in Pediatric Sepsis Based on C-reactive Protein and Ferritin Levels.

Objectives: Interest in using bedside C-reactive protein (CRP) and ferritin levels to identify patients with hyperinflammatory sepsis who might benefit from anti-inflammatory therapies has piqued with the COVID-19 pandemic experience. Our first objective was to identify patterns in CRP and ferritin trajectory among critically ill pediatric sepsis patients. We then examined the association between these different groups of patients in their inflammatory cytokine responses, systemic inflammation, and mortality risks.

Research Involvement in a Group of Registered Dietitian Nutritionists Specializing in Ketogenic Diet Therapies for Epilepsy.

Background: There is a growing need for studies on ketogenic diet (KD) therapies. Registered dietitian nutritionists (RDNs) should lead efforts to better understand the nutritional risks and benefits of the KD to inform evidence-based practices.

Objective: The purpose of this study was to explore participation in research among RDNs practicing in KD therapies for epilepsy and identify barriers to participation.

Machine learning derivation of four computable 24-h pediatric sepsis phenotypes to facilitate enrollment in early personalized anti-inflammatory clinical trials.

Background: Thrombotic microangiopathy-induced thrombocytopenia-associated multiple organ failure and hyperinflammatory macrophage activation syndrome are important causes of late pediatric sepsis mortality that are often missed or have delayed diagnosis. The National Institutes of General Medical Science sepsis research working group recommendations call for application of new research approaches in extant clinical data sets to improve efficiency of early trials of new sepsis therapies. Our objective is to apply machine learning approaches to derive computable 24-h sepsis phenotypes to facilitate personalized enrollment in early anti-inflammatory trials targeting these conditions.

Variation in pediatric cervical spine imaging across trauma centers-A cause for concern?

Background: Traumatic pediatric cervical spine injury can be challenging to diagnose, and the clinical algorithms meant to aid physicians differ from adult trauma protocols. Despite the existence of standardized guidelines, imaging decisions may vary according to physician education, subjective assessment, and experience with pediatric trauma patients. Our study investigates the rates of pediatric posttraumatic cervical spine imaging across trauma centers, hypothesizing that more specialized centers will have lower rates of advanced cervical spine imaging.

A Multicenter Network Assessment of Three Inflammation Phenotypes in Pediatric Sepsis-Induced Multiple Organ Failure.

Objectives: Ongoing adult sepsis clinical trials are assessing therapies that target three inflammation phenotypes including 1) immunoparalysis associated, 2) thrombotic microangiopathy driven thrombocytopenia associated, and 3) sequential liver failure associated multiple organ failure. These three phenotypes have not been assessed in the pediatric multicenter setting. We tested the hypothesis that these phenotypes are associated with increased macrophage activation syndrome and mortality in pediatric sepsis.

Results of the combined U.S. multicenter postapproval study of the Nit-Occlud PDA device for percutaneous closure of patent ductus arteriosus.

Objectives: To report the results of the Nit-Occlud PDA prospective postapproval study (PAS) along with a comparison to the results of the pivotal and continued access trials.

Background: The Nit-Occlud PDA (PFM Medical, Cologne, Germany), a nitinol coil patent ductus arteriosus (PDA) occluder, was approved by the Food and Drug Administration in 2013.

Methods: The PAS enrolled a total of 184 subjects greater than 6 months of age, weighing at least 5 kg, with PDAs less than 4 mm by angiography at 11 centers.

Language Analysis as a Window to Bereaved Parents' Emotions During a Parent-Physician Bereavement Meeting.

Parent-physician bereavement meetings may benefit parents by facilitating sense making, which is associated with healthy adjustment after a traumatic event. Prior research suggests a reciprocal relationship between sense making and positive emotions. We analyzed parents' use of emotion words during bereavement meetings to better understand parents' emotional reactions during the meeting and how their emotional reactions related to their appraisals of the meeting.

Chronic hypersensitivity pneumonitis caused by Saccharopolyspora rectivirgula is not associated with a switch to a Th2 response.

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease results in alveolitis and granuloma formation and may progress to a chronic form associated with fibrosis; a greater understanding of the immunopathogenic mechanisms leading to chronic HP is needed. We used the Saccharopolyspora rectivirgula (SR) mouse model of HP to determine the extent to which a switch to a Th2-type immune response is associated with chronic HP.

Limiting and Withdrawing Life Support in the PICU: For Whom Are These Options Discussed?

Objectives: Most deaths in U.S. PICUs occur after a decision has been made to limitation or withdrawal of life support.

Tacrolimus versus Cyclosporine after Hematopoietic Cell Transplantation for Acquired Aplastic Anemia.

Combinations of cyclosporine (CSP) with methotrexate (MTX) have been widely used for immunosuppression after allogeneic transplantation for acquired aplastic anemia. We compared outcomes with tacrolimus (TAC)+MTX versus CSP+MTX after transplantation from HLA-identical siblings (SIB) or unrelated donors (URD) in a retrospective cohort of 949 patients with severe aplastic anemia. Study endpoints included hematopoietic recovery, graft failure, acute graft-versus-host disease (GVHD), chronic GVHD, and mortality.

Meaning making during parent-physician bereavement meetings after a child's death.

Objective: Our goal was to identify and describe types of meaning-making processes that occur among parents during bereavement meetings with their child's intensive care physician after their child's death in a pediatric intensive care unit.

Methods: Fifty-three parents of 35 deceased children participated in a bereavement meeting with their child's physician 14.5 ± 6.

Feasibility and perceived benefits of a framework for physician-parent follow-up meetings after a child's death in the PICU.

Objective: To evaluate the feasibility and perceived benefits of conducting physician-parent follow-up meetings after a child's death in the PICU according to a framework developed by the Collaborative Pediatric Critical Care Research Network.

Design: Prospective observational study.

Setting: Seven Collaborative Pediatric Critical Care Research Network-affiliated children's hospitals.

Telehealth in developmental-behavioral pediatrics.

Developmental-behavioral pediatrics (DBP) is recognized as one of the fields with the greatest shortages of pediatric subspecialists. Families who access care often must travel great distances to tertiary academic medical centers or endure long waiting lists. While the shortages are likely to persist due to limited provider availability and an increasing number of children with developmental and behavioral disorders being identified, our field must look to innovative ways to reduce the barriers to access.

Initial treatment of epilepsy with antiepileptic drugs: pediatric issues.

The selection of an antiepileptic drug (AED) for initial treatment of epilepsy in infancy, childhood, and adolescence should ideally be made after a clear syndromic diagnosis of the patient's seizure disorder. A common cause of failure of the first AED is erroneous diagnosis. The availability of new-generation AEDs has expanded the choice of available agents with comparable efficacy for most syndromes.

Use of implantable cardioverter-defibrillators in pediatric patients.

Automatic implantable cardioverter-defibrillator use has become widespread in the prevention of sudden death in at-risk populations. The compelling safety and efficacy data in numerous large, blinded trials on adult patients have led to increasing use of these devices in pediatric patients. Although there are no prospective data to support device therapy in pediatric patients, several large, retrospective studies suggest that pediatric patients are likely to enjoy the same reduction in mortality as adult patients, with a slightly higher rate of complications from the device implant.

Protacs: chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation.

The intracellular levels of many proteins are regulated by ubiquitin-dependent proteolysis. One of the best-characterized enzymes that catalyzes the attachment of ubiquitin to proteins is a ubiquitin ligase complex, Skp1-Cullin-F box complex containing Hrt1 (SCF). We sought to artificially target a protein to the SCF complex for ubiquitination and degradation.