Mcl-1 protects eosinophils from apoptosis and exacerbates allergic airway inflammation.

Eosinophils are key effector cells in allergic diseases. Here we investigated Mcl-1 (an anti-apoptotic protein) in experimental allergic airway inflammation using transgenic overexpressing human Mcl-1 mice (hMcl-1) and reducing Mcl-1 by a cyclin-dependent kinase inhibitor. Overexpression of Mcl-1 exacerbated allergic airway inflammation, with increased bronchoalveolar lavage fluid cellularity, eosinophil numbers and total protein, and an increase in airway mucus production.

Lymphopenia in adults after the Fontan operation: prevalence and associations.

Lymphopenia is common in adults who have had a Fontan operation although its aetiology and clinical implications remain unknown. Previous work suggests an association between lymphopenia and both liver disease and splenomegaly. The objective of this study was to assess the prevalence of lymphopenia in adults with a Fontan circulation and evaluate its associations with risk factors and clinical outcomes.

Psychometric properties of the Activities Scale for Kids-performance after allogeneic hematopoietic stem cell transplantation in adolescents and children : Results of a prospective study on behalf of the German-Austrian-Swiss GVHD Consortium.

Background: The psychometric properties of an instrument, the Activity Scale for Kids-performance (ASKp), were assessed which was proposed to capture physical functioning after allogeneic hematopoietic stem cell transplantation (HSCT). Additionally, this multicenter observational prospective study investigated the influence of clinical correlates focusing on chronic graft-versus-host disease (cGVHD).

Methods: Patient-reported ASKp, clinician-reported Karnofsky/Lansky status (KPS/PSS), patient characteristics and cGVHD details were assessed of 55 patients with a median age of 12 years at baseline after day +100 post-HSCT and every 3 months during the next 18 months.

Diagnosis and management of complete tracheal rings with concurrent tracheoesophageal fistula.

Objective: Characterize patients with complete tracheal rings and tracheoesophageal fistula (TEF) and summarize management options.

Methods: A systematic review of patients under 18 years of age with complete tracheal rings and TEF was conducted. Authors were contacted for additional patient information and new cases were added.

A Randomized Trial to Evaluate OnabotulinumtoxinA for Prevention of Headaches in Adolescents With Chronic Migraine.

Objective: As a post-approval commitment, this dose-ranging study was undertaken to evaluate efficacy and safety of onabotulinumtoxinA in adolescents.

Background: In adolescents, migraine is often undiagnosed or misdiagnosed and can present unique management challenges. OnabotulinumtoxinA was approved for prevention of chronic migraine (CM) in adults in 2010.

Thromboembolic Events Are Independently Associated with Liver Stiffness in Patients with Fontan Circulation.

Thromboembolism (TE) and Fontan-associated liver disease (FALD) are common and lead to significant morbidity in Fontan circulations. Risk factors for TE and the potential link between TE and FALD are not well understood. The objective of this study was to evaluate the association between TE and the severity of FALD based on radiologic liver stiffness.

New advances in the treatment of paediatric functional abdominal pain disorders.

This Review summarises recent pharmacological and upcoming alternative interventions for children with functional abdominal pain disorders (FAPDs). Pharmacological targets include prokinetics and drugs affecting gastric accommodation to treat postprandial distress and nausea. Similarly, anti-inflammatory agents, junctional protein regulators, analgesics, secretagogues, and serotonin antagonists have a therapeutic role for irritable bowel syndrome.

Metabolic Disorders in Iranian Children with Urolithiasis.

Children with urolithiasis have a wide range of metabolic disorders which should be carefully considered. The response to medical treatment could predict recurrence and need for surgical interventions. The goal of this retrospective study is to determine the prevalence of metabolic disorders in Iranian children and assess patients' response to treatment based on the etiology of their urolithiasis.

Hearing Difficulties and Tinnitus in Construction, Agricultural, Music, and Finance Industries: Contributions of Demographic, Health, and Lifestyle Factors.

High levels of occupational noise exposure increase the risk of hearing difficulties and tinnitus. However, differences in demographic, health, and lifestyle factors could also contribute to high levels of hearing difficulties and tinnitus in some industries. Data from a subsample (n = 22,936) of the U.

EASIX and mortality after allogeneic stem cell transplantation.

Allogeneic stem cell transplantation (alloSCT) is an effective immunotherapy in patients with hematological malignancies. Endothelial dysfunction was linked to major complications after alloSCT. We asked the question if the "Endothelial Activation and Stress Index" (EASIX; [(creatinine × LDH) ÷ thrombocytes]) can predict mortality after alloSCT.

The duration of fetal antenatal steroid exposure determines the durability of preterm ovine lung maturation.

Background: Antenatal corticosteroids (ACS) are the standard of care for maturing the fetal lung and improving outcomes for preterm infants. Antenatal corticosteroid dosing remains nonoptimized, and there is little understanding of how different treatment-to-delivery intervals may affect treatment efficacy. The durability of a lung maturational response is important because the majority of women treated with antenatal corticosteroids do not deliver within the widely accepted 1- to 7-day window of treatment efficacy.

Elevated serum complement levels and higher gene copy number of complement are associated with hypertension and effective response to statin therapy in childhood-onset systemic lupus erythematosus (SLE).

Objective: Systemic lupus erythematosus (SLE) features high frequency of cardiovascular disease (CVD) and fluctuating complement levels. The clinical trial Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) aimed to evaluate whether atorvastatin treatment reduced the progression of atherosclerosis in 221 patients with childhood-onset SLE (cSLE), using carotid intima media thickness (CIMT) as surrogates. We leveraged APPLE biorepository and trial data to investigate the relationship between and CVD in cSLE.

Non-vitamin K antagonist oral anticoagulants (NOACs) for thromboembolic prevention, are they safe in congenital heart disease? Results of a worldwide study.

Background: Current guidelines consider vitamin K antagonists (VKA) the oral anticoagulant agents of choice in adults with atrial arrhythmias (AA) and moderate or complex forms of congenital heart disease, significant valvular lesions, or bioprosthetic valves, pending safety data on non-VKA oral anticoagulants (NOACs). Therefore, the international NOTE registry was initiated to assess safety, change in adherence and quality of life (QoL) associated with NOACs in adults with congenital heart disease (ACHD).

Methods: An international multicenter prospective study of NOACs in ACHD was established.

Do emissions from landfill fires affect pregnancy outcomes? A retrospective study after arson at a solid waste facility in Sicily.

Objectives: In response to public health concern about effects of arson at solid waste management plants in July 2012, we analysed vital statistics data to evaluate any potential effect on pregnancies at different gestational ages of pollutants emitted from the landfill on fire.

Setting: A community living near the largest landfill plant in Sicily.

Participants: The study group comprised 551 births, live births and stillbirths from pregnancies of mothers residing in the extra-urban exposed area, conceived during a 40 week period during which the highest fire's peak might have influenced pregnancy.

Non-vitamin K antagonist oral anticoagulants in adults with a Fontan circulation: are they safe.

Background: In Fontan patients with atrial arrhythmias (AA), non-vitamin K antagonist oral anticoagulants(NOACs) have a class III recommendation according to the Pediatric & Congenital Electrophysiology Society (PACES)/Heart Rhythm Society (HRS) guideline in 2014, due to lack of data on outcomes as opposed to evidence of harm. To address this gap in data, we investigated the safety and efficacy of NOACs in adults with a Fontan circulation in a worldwide study.

Methods: This is an international multicentre prospective cohort study, using data from the NOTE (on-vitamin K antagonist ral anticoagulants for hrombombolic prevention in patients with congenital heart disease) registry.

Occupational therapy for epidermolysis bullosa: clinical practice guidelines.

The purpose of this article is to summarize the Dystrophic Epidermolysis Bullosa Research Association (DEBRA) International evidence-based Clinical Practice Guidelines (CPGs) for the provision of occupational therapy (OT) for children and adults living with inherited epidermolysis bullosa (EB). This is a rare genetic disorder characterized by skin fragility leading to blister formation occurring spontaneously or following minor trauma. Current OT practice for persons with EB is based on anecdotal care, clinical expertise and trial and error with collaboration between caregiver and patient.

Rivaroxaban, a direct Factor Xa inhibitor, versus acetylsalicylic acid as thromboprophylaxis in children post-Fontan procedure: Rationale and design of a prospective, randomized trial (the UNIVERSE study).

Background: The Fontan procedure is the final step of the 3-stage palliative procedure commonly performed in children with single ventricle physiology. Thrombosis remains an important complication in children after this procedure. To date, guideline recommendations for the type and duration of thromboprophylaxis after Fontan surgery are mainly based on extrapolation of knowledge gained from adults at risk for thrombosis in other clinical settings.

A Rotavirus-Induced Mouse Model to Study Biliary Atresia and Neonatal Cholestasis.

Biliary atresia is a devastating neonatal cholangiopathy that affects both extra- and intrahepatic bile ducts progressing to fibrosis and end-stage liver disease by 2 years of age. Despite re-establishment of biliary drainage following a Kasai portoenterostomy (surgical procedure), many infants develop fibrosis requiring liver transplant. In the murine model of biliary atresia, rhesus rotavirus infection of newborn pups results in a cholangiopathy paralleling human biliary atresia and is used to study mechanistic aspects of the disease.

Utility Measures in Pediatric Temporary Health States: Comparison of Prone Positioning Valuation Through 5 Assessment Tools.

Background: Assessment of health-related quality of life (HRQOL or utility) is a complex issue especially in children with temporary health states.

Objectives: To assess the utility of prone positioning as a prophylactic postsurgical approach with the aid of 5 frequently used general instruments.

Methods: Visual analogue scale (VAS), time trade-off (TTO), modified TTO (m-TTO), standard gamble (SG), and chain of gambles (ChGs) instruments and interview with the parent caregivers were used to measure the HRQOL (utility value) of patients who were admitted in the surgical wards of Children's Medical Center Hospital between July and November 2015.

Changes in norovirus genotype diversity in gastroenteritis outbreaks in Alberta, Canada: 2012-2018.

Background: The emergence of norovirus genotype GII.4 variants has been associated with gastroenteritis pandemics worldwide, prompting molecular surveillance for early detection of novel strains. In this study, we aimed to analyze the outbreak activity of norovirus and characterize the norovirus strains circulating in Alberta between July 2012 and February 2018.

Health-Related Quality of Life of Pediatric Spinal Surgery Complications.

Background: Health-related quality of life (utility) measures are essential components of effectiveness analyses. The health-related quality of life of health states in pediatric patients who underwent spinal surgery have not been reported previously.

Objectives: To estimate the utility of complications after spinal surgeries and side effects of acetazolamide administration.

Antisense oligonucleotide eluforsen improves CFTR function in F508del cystic fibrosis.

Background: Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. In this study we assessed the effect of antisense oligonucleotide eluforsen on CFTR biological activity measured by Nasal Potential Difference (NPD) in patients with the most common mutation, F508del-CFTR.

Methods: This multi-centre, exploratory, open-label study recruited adults with CF homozygous or compound heterozygous for the F508del-CFTR mutation.

An open label pilot study of a dexmedetomidine-remifentanil-caudal anesthetic for infant lower abdominal/lower extremity surgery: The T REX pilot study.

Background: Concern over potential neurotoxicity of anesthetics has led to growing interest in prospective clinical trials using potentially less toxic anesthetic regimens, especially for prolonged anesthesia in infants. Preclinical studies suggest that dexmedetomidine may have a reduced neurotoxic profile compared to other conventional anesthetic regimens; however, coadministration with either anesthetic drugs (eg, remifentanil) and/or regional blockade is required to achieve adequate anesthesia for surgery. The feasibility of this pharmacological approach is unknown.