Subgroup analysis of phase 2 study of ceftolozane/tazobactam in neonates and young infants with pyelonephritis.

Ceftolozane/tazobactam is approved for the treatment of patients from birth to <18 y old with complicated urinary tract infections (cUTI). This post hoc analysis evaluated the safety, efficacy, and pharmacokinetics (PK) of ceftolozane/tazobactam compared with meropenem in neonates and young infants. NCT03230838 was a phase 2, randomized, active comparator-controlled, double-blind study of patients from birth to <18 y of age with cUTI, including pyelonephritis, given ceftolozane/tazobactam or meropenem in a 3:1 ratio.

Pharmacokinetics, Safety, and Tolerability of Imipenem/Cilastatin/Relebactam in Children with Confirmed or Suspected Gram-Negative Bacterial Infections: A Phase 1b, Open-Label, Single-Dose Clinical Trial.

Imipenem/cilastatin/relebactam is approved for the treatment of serious gram-negative bacterial infections in adults. This study assessed the pharmacokinetics (PK), safety, and tolerability of a single dose of imipenem/cilastatin/relebactam (with a fixed 2:1 ratio of imipenem/cilastatin to relebactam, and with a maximum dose of 15 mg/kg imipenem and 15 mg/kg cilastatin [≤500 mg imipenem and ≤500 mg cilastatin] and 7.5 mg/kg relebactam [≤250 mg relebactam]) in children with confirmed/suspected gram-negative bacterial infections receiving standard-of-care antibacterial therapy.

Safety and Efficacy of Ceftolozane/Tazobactam Versus Meropenem in Neonates and Children With Complicated Urinary Tract Infection, Including Pyelonephritis: A Phase 2, Randomized Clinical Trial.

Background: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, active against multidrug-resistant Gram-negative pathogens, is approved for treatment of adults with complicated urinary tract infections (cUTI). Safety and efficacy of ceftolozane/tazobactam in pediatric participants with cUTI, including pyelonephritis, were assessed.

Methods: This phase 2 study (NCT03230838) compared ceftolozane/tazobactam with meropenem for treatment of cUTI in participants from birth to <18 years of age.

Malnutrition from anorexia nervosa triggers severe complications of hereditary spherocytosis in an adolescent girl: A case report.

Hemolytic crises and aplastic crises in hereditary spherocytosis (HS) are most commonly triggered by viral infections. We present the case of an adolescent girl with HS who developed unexpected and life-threatening complications of her inherited hemolytic anemia as a consequence of anorexia nervosa and severe malnutrition.

Mutational analysis using next generation sequencing in pediatric thyroid cancer reveals BRAF and fusion oncogenes are common.

Background: We previously described mutation rates of BRAF, RAS, RET-PTC and PAX8-PPARγ in pediatric subjects with well-differentiated thyroid cancer (WDTC). We expanded the cohort adding next-generation sequencing (NGS) and assessed genotype-phenotype correlations.

Methods: Single-center retrospective cohort examining thyroidectomy tissue blocks from consecutive pediatric WDTC patients between 2001 and 2015.

Polysomnography Parameters Assessing Gas Exchange Best Predict Postoperative Respiratory Complications Following Adenotonsillectomy in Children With Severe OSA.

Study Objectives: Adenotonsillectomy (AT) is the treatment of choice for obstructive sleep apnea (OSA) in children with adenotonsillar hypertrophy. Severe OSA, identified by the apnea-hypopnea index (AHI), is a risk factor for surgical complications and AHI thresholds are used by surgeons to decide elective postoperative hospital admissions. The objective of this study was to identify the prevalence of surgical complications of AT in children with severe OSA and determine their association with specific parameters of polysomnography (PSG).

Through Thick and Thin: The In Vitro Effects of Thickeners on Infant Feed Viscosity.

Background: Gastroesophageal reflux disease (GERD) is a common problem in neonates, and current modalities for thickening human milk produce inconsistent outcomes. The objective of this in vitro study is to measure the viscosity effect of different thickening strategies.

Methods: We thickened donor human milk (DHM) and formula using various thickeners: starch-based thickeners (SBT; Thick It, rice cereal), and gum-based thickeners (GBT; xanthan gum: Simply Thick, Thicken Up Clear; carob gum: GelMix).

Neonatal Intubation Practice and Outcomes: An International Registry Study.

Background And Objectives: Neonatal tracheal intubation is a critical but potentially dangerous procedure. We sought to characterize intubation practice and outcomes in the NICU and delivery room (DR) settings and to identify potentially modifiable factors to improve neonatal intubation safety.

Methods: We developed the National Emergency Airway Registry for Neonates and collected standardized data for patients, providers, practices, and outcomes of neonatal intubation.

A guiding map for inflammation.

Biologists, physicians and immunologists have contributed to the understanding of the cellular participants and biological pathways involved in inflammation. Here, we provide a general guide to the cellular and humoral contributors to inflammation as well as to the pathways that characterize inflammation in specific organs and tissues.

Augmented Renal Clearance Using Population-Based Pharmacokinetic Modeling in Critically Ill Pediatric Patients.

Objectives: The objectives of this study were to: 1) evaluate the prevalence of augmented renal clearance in critically ill pediatric patients using vancomycin clearance; 2) derive the pharmacokinetic model that best describes vancomycin clearance in critically ill pediatric patients; and 3) correlate vancomycin clearance with creatinine clearance estimated by modified Schwartz or Cockcroft-Gault.

Design: Retrospective, two-center, cohort study from 2003 to 2016.

Setting: Clinical drug monitoring services in the PICUs at two tertiary care, teaching hospitals.

Massively parallel digital high resolution melt for rapid and absolutely quantitative sequence profiling.

In clinical diagnostics and pathogen detection, profiling of complex samples for low-level genotypes represents a significant challenge. Advances in speed, sensitivity, and extent of multiplexing of molecular pathogen detection assays are needed to improve patient care. We report the development of an integrated platform enabling the identification of bacterial pathogen DNA sequences in complex samples in less than four hours.

Outcomes of an inpatient refeeding protocol in youth with anorexia nervosa: Rady Children's Hospital San Diego/University of California, San Diego.

Background: Current guidelines for nutritional rehabilitation in hospitalized restrictive eating disorder patients recommend a cautious approach to refeeding. Several studies suggest that higher calorie diets may be safe and effective, but have traditionally excluded severely malnourished patients. The goal of this study was to evaluate the safety of a higher calorie nutritional rehabilitation protocol (NRP) in a broad sample of inpatients with restrictive eating disorders, including those who were severely malnourished.

The role of the inflammasome in patients with autoinflammatory diseases.

Autoinflammatory diseases are disorders of the innate immune system, characterized by systemic inflammation often driven by inflammasomes, and independent of infection and autoreactive antibodies or antigen-specific T cells. These diseases are increasingly recognized as disorders of immune dysregulation, presenting with a constellation of fevers, rashes, and mucosal symptoms in many cases, which suggests that the allergist/immunologist is the appropriate specialist for these patients. However, many practicing physicians are unaware of these disorders in their pediatric and adult patient populations, leading to substantial delays in diagnosis.

Cigarette Smoke Enhances the Expression of Profibrotic Molecules in Alveolar Epithelial Cells.

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal disease of unknown etiology. A growing body of evidence indicates that it may result from an aberrant activation of alveolar epithelium, which induces the expansion of the fibroblast population, their differentiation to myofibroblasts and the excessive accumulation of extracellular matrix. The mechanisms that activate the alveolar epithelium are unknown, but several studies indicate that smoking is the main environmental risk factor for the development of IPF.

Beyond the genome: epigenetic mechanisms in lung remodeling.

The lung develops from a very simple outpouching of the foregut into a highly complex, finely structured organ with multiple specialized cell types that are required for its normal physiological function. During both the development of the lung and its remodeling in the context of disease or response to injury, gene expression must be activated and silenced in a coordinated manner to achieve the tremendous phenotypic heterogeneity of cell types required for homeostasis and pathogenesis. Epigenetic mechanisms, consisting of DNA base modifications such as methylation, alteration of histones resulting in chromatin modification, and the action of noncoding RNA, control the regulation of information "beyond the genome" required for both lung modeling and remodeling.

The housekeeping gene hypoxanthine guanine phosphoribosyltransferase (HPRT) regulates multiple developmental and metabolic pathways of murine embryonic stem cell neuronal differentiation.

The mechanisms by which mutations of the purinergic housekeeping gene hypoxanthine guanine phosphoribosyltransferase (HPRT) cause the severe neurodevelopmental Lesch Nyhan Disease (LND) are poorly understood. The best recognized neural consequences of HPRT deficiency are defective basal ganglia expression of the neurotransmitter dopamine (DA) and aberrant DA neuronal function. We have reported that HPRT deficiency leads to dysregulated expression of multiple DA-related developmental functions and cellular signaling defects in a variety of HPRT-deficient cells, including human induced pluripotent stem (iPS) cells.

Systems biology of lung development and regeneration: current knowledge and recommendations for future research.

The lung begins as a simple outpouching of the foregut and develops by stages into a highly complex organ, the proper function of which is essential to life for terrestrial mammals. Interruption of normal lung development can result in death or chronic disease. Conversely, repair after lung injury, as well as many acquired diseases, involves recapitulation, often aberrant, of developmental pathways.

Executive summary: the management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America.

Evidenced-based guidelines for management of infants and children with community-acquired pneumonia (CAP) were prepared by an expert panel comprising clinicians and investigators representing community pediatrics, public health, and the pediatric specialties of critical care, emergency medicine, hospital medicine, infectious diseases, pulmonology, and surgery. These guidelines are intended for use by primary care and subspecialty providers responsible for the management of otherwise healthy infants and children with CAP in both outpatient and inpatient settings. Site-of-care management, diagnosis, antimicrobial and adjunctive surgical therapy, and prevention are discussed.

The management of community-acquired pneumonia in infants and children older than 3 months of age: clinical practice guidelines by the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America.

Evidenced-based guidelines for management of infants and children with community-acquired pneumonia (CAP) were prepared by an expert panel comprising clinicians and investigators representing community pediatrics, public health, and the pediatric specialties of critical care, emergency medicine, hospital medicine, infectious diseases, pulmonology, and surgery. These guidelines are intended for use by primary care and subspecialty providers responsible for the management of otherwise healthy infants and children with CAP in both outpatient and inpatient settings. Site-of-care management, diagnosis, antimicrobial and adjunctive surgical therapy, and prevention are discussed.

Inflammasome and IL-1beta-mediated disorders.

The NLRP3 inflammasome is an intracellular complex that regulates the release of proinflammatory cytokines such as interleukin-1beta in response to exogenous pathogens and endogenous danger signals. Evidence from studies involving human genetics, human ex vivo mononuclear cell responses, and in vivo and in vitro murine models confirms the importance of the inflammasome and interleukin-1beta in the pathogenesis of several inherited and complex diseases. The availability of several effective interleukin-1beta targeted therapies has allowed for successful proof-of-concept studies in several of these disorders.

Prostaglandin transporter expression in mouse brain during development and in response to hypoxia.

Prostaglandins (PGs) are bioactive lipid mediators released following brain hypoxic-ischemic injury. Clearance and re-uptake of these prostaglandins occur via a transmembrane prostaglandin transporter (PGT), which exchanges PG for lactate. We used Western blot analyses to examine the PGT developmental profile and its regional distribution as well as changes in transporter expression during chronic hypoxia in the neonatal mouse brain.