Consensus Treatment Plans for Severe Pediatric Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Objective: There is no standardized approach to the treatment of pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Because of the rarity of pediatric AAV, randomized trials have not been feasible. The present study of the Childhood Arthritis and Rheumatology Research Alliance (CARRA) was undertaken to establish consensus treatment plans (CTPs) for severe pediatric AAV to enable the future study of comparative effectiveness and safety.

Potential overdiagnosis of long QT syndrome using exercise stress and QT stand testing in children and adolescents with a low probability of disease.

Background: Long QT syndrome (LQTS) is a dangerous arrhythmia disorder that often presents in childhood and adolescence. The exercise stress test (EST) and QT-stand test may unmask QT interval prolongation at key heart rate transition points in LQTS, but their utility in children is debated.

Objective: To determine if the QT-stand test or EST can differentiate children with a low probability of LQTS from those with confirmed LQTS.

Maternal Diet and the Serum Metabolome in Pregnancy: Robust Dietary Biomarkers Generalizable to a Multiethnic Birth Cohort.

Background: Advances in metabolomics are anticipated to decipher associations between dietary exposures and health. Replication biomarker studies in different populations are critical to demonstrate generalizability.

Objectives: To identify and validate robust serum metabolites associated with diet quality and specific foods in a multiethnic cohort of pregnant women.

Estimated susceptibility of Canadian meningococcal B isolates to a meningococcal serogroup B vaccine (MenB-FHbp).

Background: Invasive meningococcal disease caused by Neisseria meningitidis serogroup B (MenB) remains a health risk in Canada and globally. Two MenB vaccines are now approved for use. An understanding of the genotype of Canadian strains and the potential strain coverage conferred by the MenB-FHbp vaccine is needed to inform immunization policies.

Capsule Endoscopy Complements Magnetic Resonance Enterography and Endoscopy in Evaluating Small Bowel Crohn's Disease.

Aims: Wireless capsule endoscopy (WCE) and magnetic resonance enterography (MRE) are increasingly utilized to evaluate the small bowel (SB) in Crohn's disease (CD). The primary aims were to compare the ability of WCE and MRE to detect SB inflammation in children with newly diagnosed CD, and in the terminal ileum (TI) to compare them to ileo-colonoscopy. Secondary aims were to compare diagnostic accuracy of WCE and MRE and changes in Paris classification after each study.

Intravenous immunoglobulin (IVIg) or IVIg-treated macrophages reduce DSS-induced colitis by inducing macrophage IL-10 production.

Intravenous immunoglobulin (IVIg) is used to treat immune-mediated diseases but its mechanism of action is poorly understood. We have reported that co-treatment with IVIg and lipopolysaccharide activates macrophages to produce large amounts of anti-inflammatory IL-10 in vitro. Thus, we asked whether IVIg-treated macrophages or IVIg could reduce intestinal inflammation in mice during dextran sulfate sodium (DSS)-induced colitis by inducing macrophage IL-10 production in vivo.

CAPS at 50: Now comfortably seated with the grownups.

The Canadian Association of Pediatric Surgeons was established 50 years ago, with 30 founding members. Since then, the CAPS membership has grown nearly 10-fold and has developed a global presence with representation from 15 countries. CAPS has 8 pediatric surgery training programs which contribute not only to the North American workforce, but also to profoundly underserved low and middle income countries, particularly in Africa.

Baylisascariasis: A young boy with neural larva migrans due to the emerging raccoon round worm.

A 17-month-old boy from Vancouver, Canada, presented with a 5-day history of progressive somnolence, ataxia, and torticollis. Additional investigations revealed eosinophilic encephalitis with deep white matter changes on MR imaging. On day 13, serology came back positive for antibodies.

Developing a Clinical Pathway for Somatic Symptom and Related Disorders in Pediatric Hospital Settings.

Somatic symptom and related disorders (SSRDs) are commonly encountered in pediatric hospital settings. There is, however, a lack of standardization of care across institutions for youth with these disorders. These patients are diagnostically and psychosocially complex, posing significant challenges for medical and behavioral health care providers.

Predicting Which Children with Juvenile Idiopathic Arthritis Will Not Attain Early Remission with Conventional Treatment: Results from the ReACCh-Out Cohort.

Objective: To estimate the probability of early remission with conventional treatment for each child with juvenile idiopathic arthritis (JIA). Children with a low chance of remission may be candidates for initial treatment with biologics or triple disease-modifying antirheumatic drugs (DMARD).

Methods: We used data from 1074 subjects in the Research in Arthritis in Canadian Children emphasizing Outcomes (ReACCh-Out) cohort.

IVIg and LPS Co-stimulation Induces IL-10 Production by Human Monocytes, Which Is Compromised by an FcγRIIA Disease-Associated Gene Variant.

Intravenous Immunoglobulin (IVIg) is used to treat autoimmune or inflammatory diseases, but its mechanism of action is not completely understood. We asked whether IVIg can induce interleukin-10 (IL-10) and reduce pro-inflammatory cytokine production in human monocytes, and whether this response is reduced in monocytes from people with an Fcγ receptor IIA (FcγRIIA) gene variant, which is associated with increased risk of inflammatory diseases and poor response to antibody-based biological therapy. IVIg increased IL-10 production and reduced pro-inflammatory cytokine production in response to bacterial lipopolysaccharide (LPS), which required FcγRI and FcγRIIB and activation of MAPKs, extracellular signal-regulated kinase 1/2 (ERK1/2), and p38.

Isolation and Characterization of Potentially Probiotic Bacterial Strains from Mice: Proof of Concept for Personalized Probiotics.

Modulation of the gut microbiota through the use of probiotics has been widely used to treat or prevent several intestinal diseases. However, inconsistent results have compromised the efficacy of this approach, especially in severe conditions such as inflammatory bowel disease (IBD). The purpose of our study was to develop a personalized probiotic strategy and assess its efficacy in a murine model of intestinal inflammation.

Perioperative Hypotensive Crisis in an Adolescent with a Pancreatic VIPoma and MEN1-Gene Variant.

Background: Vasoactive intestinal peptide-secreting tumours (VIPomas) lead to high-volume secretory diarrhoea with hypokalaemia, as well as hyperglycaemia and hypercalcaemia. Diagnosis is often delayed.

Case Description: We present a 13-year-old girl with a distal pancreatic VIPoma diagnosed on her second hospital presentation who became severely hypotensive on anaesthetic induction prior to tumour removal, likely due to the vasodilatory effect of supraphysiological VIP levels.

Prospective Determination of the Incidence and Risk Factors of New-Onset Uveitis in Juvenile Idiopathic Arthritis: The Research in Arthritis in Canadian Children Emphasizing Outcomes Cohort.

Objective: Identification of the incidence of juvenile idiopathic arthritis (JIA)-associated uveitis and its risk factors is essential to optimize early detection. Data from the Research in Arthritis in Canadian Children Emphasizing Outcomes inception cohort were used to estimate the annual incidence of new-onset uveitis following JIA diagnosis and to identify associated risk factors.

Methods: Data were reported every 6 months for 2 years, then yearly to 5 years.

The Muc2 mucin coats murine Paneth cell granules and facilitates their content release and dispersion.

Paneth cells are a key subset of secretory epithelial cells found at the base of small intestinal crypts. Unlike intestinal goblet cells, which secrete the mucin Muc2, Paneth cells are best known for producing an array of antimicrobial factors. We unexpectedly identified Muc2 staining localized around Paneth cell granules.

The value of patient registries in advancing pediatric surgical care.

Pediatric surgeons treat a variety of conditions that are distinguished by their low occurrence rate, complexity, and need for integrated multidisciplinary care. Although randomized controlled trials (RCTs) are considered the gold standard for generating evidence to inform best practice, they are poorly suited to rare diseases based on the variability of illness severity, unpredictability in clinical course, and the impact limitations of studying a single intervention at a time. An alternative to RCTs for comparative effectiveness research for rare diseases in pediatric surgery is the patient registry, which collects detailed and condition-specific patient level data related to illness severity, treatment, and outcome, and allows a large, disease-specific database to be created for the dual purposes of collaborative research and quality improvement across participating sites.

SLC26A3 (DRA) prevents TNF-alpha-induced barrier dysfunction and dextran sulfate sodium-induced acute colitis.

SLC26A3 encodes a Cl/HCO ion transporter that is also known as downregulated in adenoma (DRA) and is involved in HCO/mucus formation. The role of DRA in the epithelial barrier has not been previously established. In this study, we investigated the in vivo and in vitro mechanisms of DRA in the colon epithelial barrier.

Tumor necrosis factor-α acts reciprocally with solute carrier family 26, member 3, (downregulated-in-adenoma) and reduces its expression, leading to intestinal inflammation.

Solute carrier family 26, member 3 (Slc26a3), also termed downregulated-in-adenoma (DRA) is a member of the Slc26 family of anion transporters and is mutated in congenital chloride diarrhea. Our previous study demonstrated that DRA deficiency is associated with severely reduced colonic HCO3‑ secretion, a loss of colonic fluid absorption, a lack of a firmly adherent mucus layer and a severely reduced colonic mucosal resistance to dextran sodium sulfate (DSS) damage. However, the direct effect of mediators that trigger intestinal inflammatory factors on DRA has not been fully investigated.

Optimization of liposomal topotecan for use in treating neuroblastoma.

The purpose of this work was to develop an optimized liposomal formulation of topotecan for use in the treatment of patients with neuroblastoma. Drug exposure time studies were used to determine that topotecan (Hycamtin) exhibited great cytotoxic activity against SK-N-SH, IMR-32 and LAN-1 neuroblastoma human cell lines. Sphingomyelin (SM)/cholesterol (Chol) and 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC)/Chol liposomes were prepared using extrusion methods and then loaded with topotecan by pH gradient and copper-drug complexation.

Milk Fat Globule Membrane Supplementation in Formula Modulates the Neonatal Gut Microbiome and Normalizes Intestinal Development.

Breast milk has many beneficial properties and unusual characteristics including a unique fat component, termed milk fat globule membrane (MFGM). While breast milk yields important developmental benefits, there are situations where it is unavailable resulting in a need for formula feeding. Most formulas do not contain MFGM, but derive their lipids from vegetable sources, which differ greatly in size and composition.

Predicting Which Children with Juvenile Idiopathic Arthritis Will Have a Severe Disease Course: Results from the ReACCh-Out Cohort.

Objective: We studied an inception cohort of children with juvenile idiopathic arthritis (JIA) to (1) identify distinct disease courses based on changes over 5 years in 5 variables prioritized by patients, parents, and clinicians; and (2) estimate the probability of a severe disease course for each child at diagnosis.

Methods: Assessments of quality of life, pain, medication requirements, patient-reported side effects, and active joint counts were scheduled at 0, 6, 12, 18, 24, 36, 48, and 60 months. Patients who attended at least 6 assessments were included.

Outcomes of Radiofrequency Perforation for Pulmonary Atresia and Intact Ventricular Septum: A Single-Centre Experience.

Percutaneous radiofrequency perforation (RFP) of the pulmonary valve is used as a primary therapy in neonates with pulmonary atresia and intact ventricular septum (PAIVS). We sought to determine the safety and efficacy of RFP for PAIVS in a single center and assess the pre-intervention anatomical parameters associated with a biventricular outcome. We retrospectively reviewed all cases of PAIVS treated with RFP at a single center from 1999 through 2012.

Respiratory rate and pulse oximetry derived information as predictors of hospital admission in young children in Bangladesh: a prospective observational study.

Objective: Hypoxaemia is a strong predictor of mortality in children. Early detection of deteriorating condition is vital to timely intervention. We hypothesise that measures of pulse oximetry dynamics may identify children requiring hospitalisation.