Safety, tolerability, and efficacy of maralixibat in adults with primary sclerosing cholangitis: Open-label pilot study.

Background: Primary sclerosing cholangitis (PSC) is frequently associated with pruritus, which significantly impairs quality of life. Maralixibat is a selective ileal bile acid transporter (IBAT) inhibitor that lowers circulating bile acid (BA) levels and reduces pruritus in cholestatic liver diseases. This is the first proof-of-concept study of IBAT inhibition in PSC.

Maralixibat for the treatment of PFIC: Long-term, IBAT inhibition in an open-label, Phase 2 study.

Children with progressive familial intrahepatic cholestasis, including bile salt export pump (BSEP) and familial intrahepatic cholestasis-associated protein 1 (FIC1) deficiencies, suffer debilitating cholestatic pruritus that adversely affects growth and quality of life (QoL). Reliance on surgical interventions, including liver transplantation, highlights the unmet therapeutic need. INDIGO was an open-label, Phase 2, international, long-term study to assess the efficacy and safety of maralixibat in children with FIC1 or BSEP deficiencies.

Efficacy and safety of maralixibat treatment in patients with Alagille syndrome and cholestatic pruritus (ICONIC): a randomised phase 2 study.

Background: Alagille syndrome is a rare genetic disease that often presents with severe cholestasis and pruritus. There are no approved drugs for management. Maralixibat, an apical, sodium-dependent, bile acid transport inhibitor, prevents enterohepatic bile acid recirculation.

Systematic literature review on the economic, humanistic, and societal burden of heart failure in children and adolescents.

Introduction: Unlike the adult heart failure (HF) patient population, there is scarce information on the overall burden of HF in the pediatric population across geographies and within different age groups.

Areas Covered: A systematic review aims to describe and quantify the economic, humanistic, and societal burden of pediatric (age <18 years) HF on patients and caregivers. Eighteen published studies over a period of 10 years (1 January 2006-20 May 2016) were identified through Embase, Medline, Cochrane Library and selected congresses.

Systematic Literature Review on the Incidence and Prevalence of Heart Failure in Children and Adolescents.

While the epidemiology of adult heart failure has been extensively researched, this systematic review addresses the less well characterized incidence and prevalence of pediatric HF. The search strategy used Cochrane methodology and identified 83 unique studies for inclusion. Studies were categorized according to whether the HF diagnosis was reported as primary (n = 10); associated with other cardiovascular diseases (CVDs) (n = 49); or associated with non-CVDs (n = 24).

Mavoglurant in fragile X syndrome: Results of two randomized, double-blind, placebo-controlled trials.

Fragile X syndrome (FXS), the most common cause of inherited intellectual disability and autistic spectrum disorder, is typically caused by transcriptional silencing of the X-linked FMR1 gene. Work in animal models has described altered synaptic plasticity, a result of the up-regulation of metabotropic glutamate receptor 5 (mGluR5)-mediated signaling, as a putative downstream effect. Post hoc analysis of a randomized, placebo-controlled, crossover phase 2 trial suggested that the selective mGluR5 antagonist mavoglurant improved behavioral symptoms in FXS patients with completely methylated FMR1 genes.

Multitracer stable isotope quantification of arginase and nitric oxide synthase activity in a mouse model of pseudomonas lung infection.

Cystic fibrosis airways are deficient for L-arginine, a substrate for nitric oxide synthases (NOSs) and arginases. The rationale for this study was to quantify NOS and arginase activity in the mouse lung. Anesthetized unventilated mice received a primed constant stable isotope intravenous infusion containing labeled L-arginine, ornithine, and citrulline.

Lung arginase expression and activity is increased in cystic fibrosis mouse models.

The activity of arginase is increased in airway secretions of patients with cystic fibrosis (CF). Downstream products of arginase activity may contribute to CF lung disease. We hypothesized that pulmonary arginase expression and activity would be increased in mouse models of CF and disproportionally increased in CF mice with Pseudomonas aeruginosa pneumonia.

Patient-ventilator asynchrony during noninvasive pressure support ventilation and neurally adjusted ventilatory assist in infants and children.

Objectives: To document the prevalence of asynchrony events during noninvasive ventilation in pressure support in infants and in children and to compare the results with neurally adjusted ventilatory assist.

Design: Prospective randomized cross-over study in children undergoing noninvasive ventilation.

Setting: The study was performed in a PICU.

Optimizing patient-ventilator synchrony during invasive ventilator assist in children and infants remains a difficult task*.

Objectives: To document and compare the prevalence of asynchrony events during invasive-assisted mechanical ventilation in pressure support mode and in neurally adjusted ventilatory assist in children.

Design: Prospective, randomized, and crossover study.

Setting: Pediatric and Neonatal Intensive Care Unit, University Hospital of Geneva, Switzerland.

Lung-derived soluble mediators are pathogenic in ventilator-induced lung injury.

Ventilator-induced lung injury (VILI) due to high tidal volume (V(T)) is associated with increased levels of circulating factors that may contribute to, or be markers of, injury. This study investigated if exclusively lung-derived circulating factors produced during high V(T) ventilation can cause or worsen VILI. In isolated perfused mouse lungs, recirculation of perfusate worsened injury (compliance impairment, microvascular permeability, edema) induced by high V(T).

Do soluble mediators cause ventilator-induced lung injury and multi-organ failure?

Background: Significant advances in the management of patients with acute respiratory distress syndrome have been few in the recent past despite considerable efforts in clinical testing and experimental work. The biotrauma hypothesis of ventilator-associated lung injury (VALI), suggesting that mechanical ventilation induces the release of injurious mediators from the lung, implies that pharmaceutical interventions targeting these circulating pathogenic mediators would be clinically beneficial. Among the commonly reported classes of ventilation-associated mediators are cytokines, coagulation factors, hormones (e.

Management of congenital third branchial arch anomalies: a systematic review.

Objective: To systematically review the existing literature on third branchial arch anomalies and suggest guidelines for their management.

Data Sources: We searched PubMed, Medline, and Embase using Scopus, and collected additional publications cited in bibliographies. We included all English-language articles and all foreign-language articles with an English abstract.

Management of congenital fourth branchial arch anomalies: a review and analysis of published cases.

Background/purpose: Congenital fourth branchial arch anomalies are uncommon entities, heretofore described only in case reports, affecting primarily children, and typically presenting as a cervical inflammatory process. The aim of the study was to collect appropriate data on the diagnosis, treatment, and outcome of this condition and to suggest guidelines for its management.

Methods: We conducted a structured review of the literature for cases explicitly identified as congenital fourth branchial arch anomalies or meeting anatomical criteria for this condition.

Volume-targeted modes of modern neonatal ventilators: how stable is the delivered tidal volume?

Objective: Volume-targeted modes are designed to deliver a constant tidal volume (V(t)) at lowest possible pressure independently of changes in compliance, resistance, and leak of the respiratory system. We examined whether these volume-targeted modes respond rapidly enough to sudden changes in respiratory mechanics (e.g.

Trends in antibiotic resistance of respiratory tract pathogens in children in Geneva, Switzerland.

Unlabelled: Bacteria increasingly resistant to antibiotics are a major treatment concern of respiratory tract pathogens in children. The aim of this study was to assess the trends of resistance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis to several classes of antibiotics in children<16 years of age and to compare its prevalence with surrounding countries. We studied retrospectively the susceptibility of respiratory tract pathogens isolated from specimens collected from patients at the Geneva Children's Hospital between 1989 and 2004.