Landscape of TPMT and NUDT15 Pharmacogenetic Variation in a Cohort of Canadian Pediatric Inflammatory Bowel Disease Patients.

Background: Patients with inflammatory bowel disease (IBD) exhibit considerable interindividual variability in medication response, highlighting the need for precision medicine approaches to optimize and tailor treatment. Pharmacogenetics (PGx) offers the ability to individualize dosing by examining genetic factors underlying the metabolism of medications such as thiopurines. Pharmacogenetic testing can identify individuals who may be at risk for thiopurine dose-dependent adverse reactions including myelosuppression.

Microbiota signatures and mucosal healing in the use of enteral nutrition therapy . corticosteroids for the treatment of children with Crohn's disease: a systematic review and meta-analysis.

Corticosteroids (CS) and exclusive and partial enteral nutrition (EEN and PEN) are effective therapies in paediatric Crohn's disease (CD). This systematic review of randomised controlled trials (RCT) and cohort studies analyses the impact of EEN/PEN . CS on intestinal microbiota, mucosal healing as well as other clinically important outcomes, including clinical remission, relapse, adherence, adverse events and health-related quality of life (HRQL) in paediatric CD.

Venous thromboembolism in pediatric inflammatory bowel disease: an 11-year population-based nested case-control study in Canada.

To investigate the occurrence of venous thromboembolism (VTE), clinical characteristics, risk factors, treatment outcomes, and anticoagulation safety in pediatric inflammatory bowel disease (IBD) over an 11-year period. A nested case-control study within an identified cohort was performed amongst children with IBD from 2009 to 2020 in Canada. There were 890 hospitalizations during the study period, and 15 venous thromboembolic events (1.

Nutritional Therapies and Their Influence on the Intestinal Microbiome in Pediatric Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic, autoimmune disorder of the gastrointestinal tract with numerous genetic and environmental risk factors. Patients with Crohn's disease (CD) or ulcerative colitis (UC) often demonstrate marked disruptions of their gut microbiome. The intestinal microbiota is strongly influenced by diet.

Effect of Exclusive Enteral Nutrition and Corticosteroid Induction Therapy on the Gut Microbiota of Pediatric Patients with Inflammatory Bowel Disease.

Introduction: Exclusive enteral nutrition (EEN) and corticosteroids (CS) are effective induction therapies for pediatric Crohn's Disease (CD). CS are also therapy for ulcerative colitis (UC). Host-microbe interactions may be able to explain the effectiveness of these treatments.

Hydrogels Embedded With Melittin and Tobramycin Are Effective Against Biofilms in an Animal Wound Model.

We demonstrate that the antimicrobial peptide, melittin, is effective alone and in combination with the aminoglycosides tobramycin to kill growing as biofilms both and . Melittin and tobramycin show enhanced activity in combination at micromolar concentrations, resulting in a 2-log reduction in the number of cells within mature PAO1 biofilms after 6-h of treatment. Alternatively, either agent alone resulted in half-a-log reduction.

The ionophore oxyclozanide enhances tobramycin killing of Pseudomonas aeruginosa biofilms by permeabilizing cells and depolarizing the membrane potential.

Objectives: To assess the ability of oxyclozanide to enhance tobramycin killing of Pseudomonas aeruginosa biofilms and elucidate its mechanism of action.

Methods: Twenty-four hour biofilms formed by the P. aeruginosa strain PAO1 and cystic fibrosis (CF) isolates were tested for susceptibility to oxyclozanide and tobramycin killing using BacTiter-Glo™ and cfu.

Triclosan Is an Aminoglycoside Adjuvant for Eradication of Pseudomonas aeruginosa Biofilms.

One of the most important clinical obstacles in cystic fibrosis (CF) treatment is antibiotic treatment failure due to biofilms produced by The ability of this pathogen to survive eradication by tobramycin and pathoadapt into a hyperbiofilm state leading to chronic infections is key to its success. Retrospective studies have demonstrated that preventing this pathoadaptation by improving eradication is essential to extend the lives of CF patients. To identify adjuvants that enhance tobramycin eradication of , we performed a high-throughput screen of 6,080 compounds from four drug-repurposing libraries.

Enteral nutritional therapy for induction of remission in Crohn's disease.

Background: Corticosteroids are often preferred over enteral nutrition (EN) as induction therapy for Crohn's disease (CD). Prior meta-analyses suggest that corticosteroids are superior to EN for induction of remission in CD. Treatment failures in EN trials are often due to poor compliance, with dropouts frequently due to poor acceptance of a nasogastric tube and unpalatable formulations.

Barriers and Facilitators to a Good Bowel Preparation for Colonoscopy in Children: A Qualitative Study.

Background: A well-visualized colon during colonoscopy has a direct impact on interpretation of findings and need for repeat procedure. Studies have been conducted in the adult population to assess factors contributing to improved bowel preparation. The primary aim of this study was to determine barriers and facilitators to good preparation in children.

Infliximab-induced psoriasis and psoriasiform skin lesions in pediatric Crohn disease and a potential association with IL-23 receptor polymorphisms.

Background: Infliximab (IFX), an established therapy for pediatric Crohn disease (CD), is also efficacious in treating psoriasis, a skin disorder, in which tumor necrosis factor-α is implicated pathogenically. Paradoxically, there have been numerous reports of new-onset psoriasis following tumor necrosis factor-α antagonist therapy in adult patients with inflammatory bowel disease, but pediatric data are sparse.

Methods: A retrospective review of all IFX-treated patients with CD, who subsequently developed psoriasis, at a single pediatric inflammatory bowel disease center, was performed.

Drug-induced esophageal injury with an occult vascular ring.

Drug-induced esophageal injury is an under-recognized clinical problem, and is associated with antibiotic use in more than 50% of cases. The current report describes a teenage girl who presented with symptoms of pill-induced esophagitis following doxycycline use. Subsequent investigations identified a previously undiagnosed vascular ring.

IL-10R polymorphisms are associated with very-early-onset ulcerative colitis.

Background: Interleukin-10 (IL-10) signaling genes are attractive inflammatory bowel disease (IBD) candidate genes as IL-10 restricts intestinal inflammation, IL-10 polymorphisms have been associated with IBD in genome-wide association studies, and mutations in IL-10 and IL-10 receptor (IL-10R) genes have been reported in immunodeficient children with severe infantile-onset IBD. Our objective was to determine if IL-10R polymorphisms were associated with early-onset IBD (EO-IBD) and very-early-onset IBD (VEO-IBD).

Methods: Candidate-gene analysis of IL10RA and IL10RB was performed after initial sequencing of an infantile onset-IBD patient identified a novel homozygous mutation.

Determinants of quality of life in children with chronic somatic disease: pilot data from the GapS Questionnaire.

Purpose: Quality of life (QoL) is a ubiquitous yet poorly defined concept; the precise determinants of QoL are rarely identified. We used pilot data from the GapS Questionnaire to investigate the most important determinants of QoL in children with chronic somatic illness.

Methods: We enrolled 92 participants including 60 parents and 32 of their children.

Assessment of knowledge in adolescents with inflammatory bowel disease using a novel transition tool.

Background: In the transition from pediatric to adult care, patients are expected to increase their level of self-care. Knowledge of disease characteristics, medications, and resources is crucial. This study evaluated the knowledge of adolescents with inflammatory bowel disease (IBD) and their parents in four major domains: disease characteristics, treatments, medical history, and health services resources.

Vulvar inflammation as the only clinical manifestation of Crohn disease in an 8-year-old girl.

Recognition of Crohn disease in children who present with cutaneous vulvar lesions as their initial clinical manifestation is often difficult. We report here the case of an 8-year-old girl with chronic vulvar edema, which on biopsy revealed granulomatous inflammation of the vulva. Further investigation and biopsy of the terminal ileum demonstrated similar findings and was consistent with a diagnosis of Crohn disease.

Tubulointerstitial nephritis as an extraintestinal manifestation of Crohn's disease.

Background: A 12-year-old boy presented to hospital with a 6-month history of crampy pre-defecation abdominal pain, non-bloody diarrhea, anorexia and weight loss. Investigations revealed hypochromic microcytic anemia, a low serum iron level, a low serum ferritin level and an elevated serum creatinine level. Histopathological examination of tissue specimens obtained at esophagogastroduodenoscopy and colonoscopy revealed features of Crohn's disease, and a renal biopsy demonstrated tubulointerstitial nephritis.

Development, validation, and evaluation of a pediatric ulcerative colitis activity index: a prospective multicenter study.

Background And Aims: Colonoscopic appearance, the primary measure of disease activity in adult ulcerative colitis, is less acceptable to children. Our aim was to develop a noninvasive activity index of pediatric ulcerative colitis.

Methods: Item selection was performed judgmentally using a Delphi group of 36 experts in pediatric inflammatory bowel disease.

Enteral nutritional therapy for induction of remission in Crohn's disease.

Background: The role of enteral nutrition in Crohn's disease is controversial. Increasing research on the mechanisms by which nutritional therapy improves the clinical well being of patients with Crohn's disease has led to novel formula design and trials comparing two different forms of enteral nutrition. This meta-analysis aims to provide an update on the existing effectiveness data for both corticosteroids versus enteral nutrition and for one form of enteral nutrition versus another for inducing remission of active Crohn's disease.