Association Between Nasopharyngeal Colonization and Clinical Outcome in Children With Acute Otitis Media.

Background: Young children with acute otitis media (AOM) frequently exhibit nasopharyngeal colonization with either Streptococcus pneumoniae, Haemophilus influenzae or both pathogens. We aimed to determine if antibiotics could be spared or shortened in those without nasopharyngeal colonization with either pathogen.

Methods: In 2 separate randomized clinical trials in children aged 6-23 months with stringently-diagnosed AOM, we performed bacterial cultures on nasopharyngeal specimens collected at the time of diagnosis.

Roadmap for Advancing Pre-Clinical Science in Traumatic Brain Injury.

Pre-clinical models of disease have long played important roles in the advancement of new treatments. However, in traumatic brain injury (TBI), despite the availability of numerous model systems, translation from bench to bedside remains elusive. Integrating clinical relevance into pre-clinical model development is a critical step toward advancing therapies for TBI patients across the spectrum of injury severity.

Circulating GFAP and Iba-1 levels are associated with pathophysiological sequelae in the thalamus in a pig model of mild TBI.

Serum biomarkers are promising tools for evaluating patients following traumatic brain injury (TBI). However, their relationship with diffuse histopathology remains unclear. Additionally, translatability is a focus of neurotrauma research, however, studies using translational animal models are limited.

Intra-Amniotic Sildenafil Treatment Promotes Lung Growth and Attenuates Vascular Remodeling in an Experimental Model of Congenital Diaphragmatic Hernia.

Background: Defective lung development resulting in lung hypoplasia and an attenuated and hypermuscularized pulmonary vasculature contributes to significant postnatal mortality in congenital diaphragmatic hernia (CDH). We hypothesize that deficient embryonic pulmonary blood flow contributes to defective lung development in CDH, which may therefore be ameliorated via enhancement of embryonic pulmonary blood flow.

Methods: The mouse nitrofen model of CDH was utilized to measure embryonic pulmonary blood flow by in utero intracardiac injection of FITC-labeled tomato lectin and color-flow Doppler ultrasound.

Four Biomarkers Linked to Activation of Cluster of Differentiation 8-Positive Lymphocytes Predict Clinical Outcomes in Pediatric Acute Liver Failure.

Background And Aims: Immune dysregulation contributes to the pathogenesis of pediatric acute liver failure (PALF). Our aim was to identify immune activation markers (IAMs) in PALF that are associated with a distinct clinical phenotype and outcome.

Approach And Results: Among 47 PALF study participants, 12 IAMs collected ≤6 days after enrollment were measured by flow cytometry and IMMULITE assay on blood natural killer and cluster of differentiation 8-positive (CD8 ) lymphocytes and subjected to unsupervised hierarchical analyses.

Liver Transplant Listing in Pediatric Acute Liver Failure: Practices and Participant Characteristics.

Liver transplant (LT) decisions in pediatric acute liver failure (PALF) are complex. Three phases of the PALF registry, containing data on 1,144 participants over 15 years, were interrogated to characterize clinical features associated with listing status. A decrease in the cumulative incidence of listing (P < 0.

Lack of Benefit on Brain Edema, Blood-Brain Barrier Permeability, or Cognitive Outcome in Global Inducible High Mobility Group Box 1 Knockout Mice Despite Tissue Sparing after Experimental Traumatic Brain Injury.

High mobility group box 1 (HMGB1) is a prototypical danger-associated molecular pattern molecule that is considered a late mediator of neuro-inflammation after traumatic brain injury (TBI). Prior studies have suggested that targeting HMGB1 may lead to neuroprotective effects, but none of these studies have reported cognitive outcomes. We hypothesized that loss of HMGB1 before and after TBI would markedly attenuate post-traumatic brain edema, blood-brain barrier (BBB) permeability, improve functional deficits and long-term neuropathology versus control mice.

A Computable Definition of Sepsis Facilitates Screening and Performance Improvement Tracking.

Background: Sepsis kills almost 5,000 children annually, accounting for 16% of pediatric health care spending in the United States.

Objectives: We sought to identify sepsis within the Electronic Health Record (EHR) of a quaternary children's hospital to characterize disease incidence, improve recognition and response, and track performance metrics.

Methods: Methods are organized in a plan-do-study-act cycle.

A Learning Collaborative Approach Increases Specificity of Diagnosis of Acute Liver Failure in Pediatric Patients.

Background & Aims: Many pediatric patients with acute liver failure (PALF) do not receive a specific diagnosis (such as herpes simplex virus or Wilson disease or fatty acid oxidation defects)-they are left with an indeterminate diagnosis and are more likely to undergo liver transplantation, which is contraindicated for some disorders. Strategies to facilitate complete diagnostic testing should increase identification of specific liver diseases and might reduce liver transplantation. We investigated whether performing recommended age-specific diagnostic tests (AS-DTs) at the time of hospital admission reduces the percentage PALFs with an indeterminate diagnosis.

Successful Management of Chylothorax With Etilefrine: Case Report in 2 Pediatric Patients.

Chylothorax is defined as the accumulation of chyle within the pleural space. Originally described in 1917 by Pisek, it is the most common cause of pleural effusion in the neonatal period. The leading cause of chylothorax is laceration of the thoracic duct during surgery, which occurs in 0.

Sternoclavicular Arthritis as a Clinical Presentation for Lyme Disease.

Lyme disease is caused by and can lead to dermatologic, neurologic, cardiac, and musculoskeletal manifestations. The arthritis of Lyme disease is typically monoarticular, with the knee being most commonly involved. Lyme arthritis of small joints has not previously been well described.

Making Residents Part of the Safety Culture: Improving Error Reporting and Reducing Harms.

Objectives: Reporting medical errors is a focus of the patient safety movement. As frontline physicians, residents are optimally positioned to recognize errors and flaws in systems of care. Previous work highlights the difficulty of engaging residents in identification and/or reduction of medical errors and in integrating these trainees into their institutions' cultures of safety.

The effect of obesity, weight gain, and weight loss on asthma inception and control.

Purpose Of Review: There is ample and growing evidence that obesity increases the risk of asthma and morbidity from asthma. Here, we review recent clinical evidence supporting a causal link between obesity and asthma, and the mechanisms that may lead to 'obese asthma'.

Recent Findings: Although in some children obesity and asthma simply co-occur, those with 'obese asthma' have increased asthma severity, lower quality of life, and reduced medication response.

De Novo Truncating Variants in SON Cause Intellectual Disability, Congenital Malformations, and Failure to Thrive.

SON is a key component of the spliceosomal complex and a critical mediator of constitutive and alternative splicing. Additionally, SON has been shown to influence cell-cycle progression, genomic integrity, and maintenance of pluripotency in stem cell populations. The clear functional relevance of SON in coordinating essential cellular processes and its presence in diverse human tissues suggests that intact SON might be crucial for normal growth and development.

Development of Risk Indices for Neonatal Respiratory Extracorporeal Membrane Oxygenation.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has saved thousands of newborns. Population comparisons for research and quality initiatives require risk-matching, but no indices exist for this population. We sought to create a pre-ECMO risk index using the registry data from the Extracorporeal Life Support Organization.

Plasma Mitochondrial DNA--a Novel DAMP in Pediatric Sepsis.

Mitochondrial DNA (mtDNA) is a novel danger-associated molecular pattern that on its release into the extracellular milieu acts via toll-like receptor-9, a pattern recognition receptor of the immune system. We hypothesized that plasma mtDNA concentrations will be elevated in septic children, and these elevations are associated with an increase in the severity of illness. In a separate set of in vitro experiments, we test the hypothesis that exposing peripheral blood mononuclear cells (PBMC) to mtDNA activates the immune response and induces tumor necrosis factor (TNF) release.

Risk Factors for Recurrent Urinary Tract Infection and Renal Scarring.

Objectives: To identify risk factors for recurrent urinary tract infection (UTI) and renal scarring in children who have had 1 or 2 febrile or symptomatic UTIs and received no antimicrobial prophylaxis.

Methods: This 2-year, multisite prospective cohort study included 305 children aged 2 to 71 months with vesicoureteral reflux (VUR) receiving placebo in the RIVUR (Randomized Intervention for Vesicoureteral Reflux) study and 195 children with no VUR observed in the CUTIE (Careful Urinary Tract Infection Evaluation) study. Primary exposure was presence of VUR; secondary exposures included bladder and bowel dysfunction (BBD), age, and race.

A novel maternally inherited 8q24.3 and a rare paternally inherited 14q23.3 CNVs in a family with neurodevelopmental disorders.

A 7-year-old female with developmental delay (DD), autism spectrum disorder (ASD), intellectual disability (ID), attention deficit hyperactivity disorder (ADHD), and seizures was referred to our laboratory for oligomicroarray analysis. The analysis revealed a 540 kb microdeletion in the chromosome 8q24.3 region (143,610,058-144,150,241) encompassing multiple genes.

Poly(ADP-ribose) polymerase 1-sirtuin 1 functional interplay regulates LPS-mediated high mobility group box 1 secretion.

Pathophysiological conditions that lead to the release of the prototypic damage-associated molecular pattern molecule high mobility group box 1 (HMGB1) also result in activation of poly(ADP-ribose) polymerase 1 (PARP1; now known as ADP-ribosyl transferase 1 [ARTD1]). Persistent activation of PARP1 promotes energy failure and cell death. The role of poly(ADP-ribosyl)ation in HMGB1 release has been explored previously; however, PARP1 is a versatile enzyme and performs several other functions including cross-talk with another nicotinamide adenine dinucleotide- (NAD(+)) dependent member of the Class III histone deacetylases (HDACs), sirtuin-1 (SIRT1).

Bcl10 mediates angiotensin II-induced cardiac damage and electrical remodeling.

Angiotensin (Ang) II is a potent mediator of both hypertension and cardiac damage; however, the mechanisms by which this occur remain unclear. B-cell lymphoma/leukemia 10 (Bcl10) is a member of the CBM signalosome, which links Ang II and nuclear factor-κB signaling. We hypothesized that Bcl10 is pivotal in the pathogenesis of Ang II-induced cardiac damage.

Emergence of Streptococcus pneumoniae serogroups 15 and 35 in nasopharyngeal cultures from young children with acute otitis media.

Background: Surveillance of children with acute otitis media (AOM) for nasopharyngeal colonization with Streptococcus pneumoniae before, during and after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7) indicated the near-complete elimination of PCV7 strains and the emergence of pneumococcal serotype 19A.

Methods: To determine effects of the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal nasopharyngeal colonization, we obtained nasopharyngeal cultures from 228 children 6 through 23 of age months presenting with a new episode of AOM during 2012 and 2013 and enrolled in an ongoing clinical trial of antimicrobial efficacy. All children had received at least 2 doses of PCV13.

Cerebrospinal fluid mitochondrial DNA: a novel DAMP in pediatric traumatic brain injury.

Danger-associated molecular patterns (DAMPs) are nuclear or cytoplasmic proteins that are released from the injured tissues and activate the innate immune system. Mitochondrial DNA (mtDNA) is a novel DAMP that is released into the extracellular milieu subsequent to cell death and injury. We hypothesized that cell death within the central nervous system in children with traumatic brain injury (TBI) would lead to the release of mtDNA into the cerebrospinal fluid (CSF) and has the potential to predict the outcome after trauma.