A5002988667- Cystic Fibrosis Research Advances
- Pancreatitis Pathology and Treatment
- Neonatal Respiratory Health Research
- Tracheal and airway disorders
- Pediatric Hepatobiliary Diseases and Treatments
- Pancreatic and Hepatic Oncology Research
- Asthma and respiratory diseases
- Gastrointestinal disorders and treatments
- Diabetes and associated disorders
- Inhalation and Respiratory Drug Delivery
- Child Nutrition and Feeding Issues
- Intestinal Malrotation and Obstruction Disorders
- Congenital Ear and Nasal Anomalies
- Childhood Cancer Survivors' Quality of Life
- Infant Development and Preterm Care
- IgG4-Related and Inflammatory Diseases
- Infant Nutrition and Health
- Pediatric health and respiratory diseases
- Esophageal and GI Pathology
- Digestive system and related health
- Ion Transport and Channel Regulation
- Child and Adolescent Health
- Advanced biosensing and bioanalysis techniques
- Adolescent and Pediatric Healthcare
- Neuroendocrine Tumor Research Advances
University of Toronto
2015-2024
SickKids Foundation
2015-2024
Hospital for Sick Children
2015-2024
Rush Children's Hospital
2023
Rush University Medical Center
2023
Yale University
2023
University of North Carolina Hospitals
2023
University of North Carolina at Chapel Hill
2023
Translational Research Institute
2023
The University of Texas MD Anderson Cancer Center
2022
Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator recently approved for patients with CF age 6 and older the G551D mutation.To evaluate ivacaftor in postapproval setting determine mechanism of action response clinically relevant markers.We conducted longitudinal cohort study 2012-2013 no prior exposure to ivacaftor. Study assessments were performed at baseline, 1, 3, months after initiation. Substudies evaluated mucociliary clearance, β-adrenergic sweat...
Pediatric acute recurrent pancreatitis (ARP) and chronic (CP) are poorly understood.To characterize identify risk factors associated with ARP CP in childhood.A multinational cross-sectional study of children or at the time enrollment to INSPPIRE (International Study Group Pancreatitis: In Search for a Cure) participant institutions Consortium. From August 22, 2012, February 8, 2015, 155 146 (aged ≤19 years) were enrolled. Their demographic clinical information was entered into REDCap...
Although the incidence of acute pancreatitis (AP) in children is increasing, management recommendations rely on adult published guidelines. Pediatric-specific are needed.The North American Society for Pediatric Gastroenterology, Hepatology and Nutrition Pancreas committee performed a MEDLINE review using several preselected key terms relating to considerations pediatric AP. The literature was summarized, quality evidence reviewed, statements developed. authorship met discuss evidence,...
B-cell-depletion therapy with rituximab is efficacious against steroid-dependent nephrotic syndrome (NS) in children and adults. Safety data are limited. Results of small studies have suggested that usually well tolerated but adverse events (such as severe mucocutaneous reactions, fatal infusion progressive multifocal leukoencephalopathy, bowel perforation) can occur. We report here the first case (to our knowledge) a pediatric patient refractory minimal-change NS who developed...
Cystic fibrosis (CF) is caused by mutations in the cystic transmembrane conductance regulator (CFTR) gene. Next to progressive airway disease, CF also associated with intestinal inflammation and dysbiosis. Ivacaftor, a CFTR potentiator, has improved pulmonary nutritional status but its effects on microbiota are unclear. Hence, we assessed changes microbial communities (16S rRNA variable 3 gene region) inflammatory markers (calprotectin M2-pyruvate kinase [M2-PK]) 16 individuals (8 children 8...
Positive results in pre-clinical studies of the triple combination elexacaftor, tezacaftor and ivacaftor, performed airway epithelial cell cultures obtained from patients harbouring class II cystic fibrosis transmembrane conductance regulator (CFTR) mutation F508del-CFTR, translated to impressive clinical outcomes for subjects carrying this trials approval Trikafta.Encouraged by correlation, we were prompted evaluate effect ivacaftor on primary nasal individuals with rare CF-causing...
OBJECTIVES:. To prospectively study infants with an inconclusive diagnosis of cystic fibrosis (CF) identified by newborn screening (NBS; "CF screen positive, diagnosis" [CFSPID]) for disease manifestations.METHODS:. Infants CFSPID and CF based on NBS from 8 centers were evaluated monitored. Genotype, phenotype, repeat sweat test, serum trypsinogen, microbiology data compared between subjects who did (CFSPID→CF) not (CFSPID→CFSPID) fulfill the criteria during first 3 years life.RESULTS:....
The most common mutation causing cystic fibrosis (CF), F508del, impairs conformational maturation of CF transmembrane conductance regulator (CFTR), thereby reducing its functional expression on the surface epithelia. Corrector compounds including C18 (VRT-534) and VX-809 have been shown to partially rescue misfolding F508del-CFTR enhance forward trafficking cell surface. Now, we show that there is an additional action conferred by these beyond their role in improving biosynthetic assembly....
Abstract The combination therapy of lumacaftor and ivacaftor (Orkambi ® ) is approved for patients bearing the major cystic fibrosis ( CF mutation: ΔF508 . It has been predicted that Orkambi could treat with rarer mutations similar “theratype”; however, a standardized approach confirming efficacy in these cohorts not reported. Here, we demonstrate rare c.3700 A>G, causing protein misprocessing altered channel function—similar to ΔF508‐ CFTR , are unlikely yield robust response. While...
Cystic fibrosis is realizing the promise of personalized medicine.Recent advances in drug development that target causal CFTR directly result lung function improvement, but variability response demanding better prediction outcomes to improve management decisions.The genetic modifier SLC26A9 contributes disease severity CF pancreas and intestine at birth here we assess its relationship with therapeutic airways.SLC26A9 association was assessed individuals from Canadian French Gene Modifier...
Glucagon-like peptide-2 (GLP-2) is an intestinal growth-promoting hormone used to treat short bowel syndrome. GLP-2 promotes growth through a mechanism that involves both IGF-1 and the intestinal-epithelial receptor (IE-IGF-1R). also enhances barrier function, but unknown mechanism. We therefore hypothesized GLP-2-enhanced function requires IE-IGF-1R mediated alterations in expression localization of tight junction proteins. Conditional IE-IGF-1R-null control mice were treated with vehicle...
Rationale: β-Adrenergically induced sweat secretion offers an expedient method to assess native cystic fibrosis transmembrane conductance regulator (CFTR) secretory function in vivo.Objectives: To evaluate the sensitivity, specificity, and reliability of a test based on activity CFTR gland.Methods: Primary validation trials with prospectively ascertained healthy control subjects, obligate heterozygotes, patients CFTR-related disorder CF (pancreatic sufficient insufficient).Measurements Main...
Pulmonary disease is the major cause of morbidity and mortality in patients with cystic fibrosis, a caused by mutations Cystic Fibrosis Transmembrane conductance Regulator (CFTR) gene. Heterogeneity CFTR genotype-phenotype relationships affected individuals plus escalation drug discovery targeting specific highlights need to develop robust vitro platforms which stratify therapeutic options using relevant tissue. Toward this goal, we adapted fluorescence plate reader assay apical...
The sweat chloride test remains the gold standard for confirmatory diagnosis of cystic fibrosis (CF) in support universal newborn screening programs. However, it provides ambiguous results intermediate cases while not reflecting disease progression when classifying complex CF spectrum given pleiotropic effects gene modifiers and environment. Herein we report first characterization metabolome from screen-positive infants identify metabolites associated with status that complement testing....
ABSTRACT Objectives: Acute recurrent pancreatitis (ARP) and chronic (CP) are rare poorly understood diseases in children. Better understanding of these disorders can only be accomplished via a multicenter, structured, data collection approach. Methods: The In ternational S tudy Group P ediatric ancreatitis: I n Search for Cu re (INSPPIRE) consortium was created to investigate the epidemiology, etiologies, pathogenesis, natural history, outcomes pediatric ARP CP. Patient physician...
BackgroundThe nonsense mutation, c.3846G>A (aka: W1282X-CFTR) leads to a truncated transcript that is susceptible nonsense-mediated decay (NMD) and produces shorter protein unstable lacks normal channel activity in patient-derived tissues. However, if overexpressed heterologous expression system, the mutant has been shown mediate CFTR function following addition of potentiators. In this study, we asked quadruple combination small molecules together inhibit mediated decay, stabilize both...