Objective: Epigenetic mechanisms, including DNA methylation (DNAm), have been proposed to play a key role in Crohn's disease (CD) pathogenesis. However, the specific cell types and pathways affected as well as their potential impact on disease phenotype and outcome remain unknown. We set out to investigate the role of intestinal epithelial DNAm in CD pathogenesis.
View Article and Find Full Text PDFCell Mol Gastroenterol Hepatol
November 2022
Background & Aims: Human intestinal epithelial organoids (IEOs) are a powerful tool to model major aspects of intestinal development, health, and diseases because patient-derived cultures retain many features found in vivo. A necessary aspect of the organoid model is the requirement to expand cultures in vitro through several rounds of passaging. This is of concern because the passaging of cells has been shown to affect cell morphology, ploidy, and function.
View Article and Find Full Text PDFBackground And Aims: Thromboprophylaxis use in paediatric inflammatory bowel disease [IBD] is inconsistent. Current guidelines only support treating children with acute severe colitis with risk factors. We convened an international RAND panel to explore thromboprophylaxis in paediatric IBD inpatients in the context of new evidence.
View Article and Find Full Text PDFObjectives: Patients with paediatric inflammatory bowel disease (IBD) constitute one of the largest cohorts requiring transition from paediatric to adult services. Standardised transition care improves short and long-term patient outcomes. This study aimed to detail the current state of transition services for IBD in the United Kingdom (UK).
View Article and Find Full Text PDFObjective: Paediatric acute severe colitis (ASC) management during the novel SARS-CoV-2/COVID-19 pandemic is challenging due to reliance on immunosuppression and the potential for surgery. We aimed to provide COVID-19-specific guidance using the European Crohn's and Colitis Organisation/European Society for Paediatric Gastroenterology, Hepatology and Nutrition guidelines for comparison.
Design: We convened a RAND appropriateness panel comprising 14 paediatric gastroenterologists and paediatric experts in surgery, rheumatology, respiratory and infectious diseases.
Background: COVID-19 has impacted on healthcare provision. Anecdotally, investigations for children with inflammatory bowel disease (IBD) have been restricted, resulting in diagnosis with no histological confirmation and potential secondary morbidity. In this study, we detail practice across the UK to assess impact on services and document the impact of the pandemic.
View Article and Find Full Text PDFThe colorectal adenoma-carcinoma sequence has provided a paradigmatic framework for understanding the successive somatic genetic changes and consequent clonal expansions that lead to cancer. However, our understanding of the earliest phases of colorectal neoplastic changes-which may occur in morphologically normal tissue-is comparatively limited, as for most cancer types. Here we use whole-genome sequencing to analyse hundreds of normal crypts from 42 individuals.
View Article and Find Full Text PDFCerebral vein thrombosis is a severe complication of inflammatory bowel disease, can cause non-specific symptoms and hence lead to delay in diagnosis. We report the case of an adolescent with inflammatory bowel disease who developed extensive cerebral vein thrombosis requiring a ventriculoperitoneal shunt. Diagnosis was markedly delayed due to repeated misinterpretation of clinical signs and laboratory findings and the lack of reconsidering the working diagnosis despite the involvement of several medical subspecialties.
View Article and Find Full Text PDFThe disease course of children with ulcerative colitis (UC) varies substantially. Published data on predictors of disease outcomes in children remain scarce. We validate clinical predictors of outcomes in 93 children with UC in a single centre (age range: 2-18 years, minimum follow-up: 18 months).
View Article and Find Full Text PDFObjective: The aim of this study was to measure the effectiveness, safety, and use of anti-tumor necrosis Factor (TNF) therapy in pediatric inflammatory bowel disease in the United Kingdom (UK).
Methods: Prospective UK audit of patients newly starting anti-TNF therapy. Disease severity was assessed using Physician Global Assessment +/or the Paediatric Crohn Disease Activity Index.
Background: We studied the expression of sulphated glycosaminoglycans (GAGs) in coeliac disease (CD) mucosa, as they are critical determinants of tissue volume, which increases in active disease. We also examined mucosal expression of IL-6, which stimulates excess GAG synthesis in disorders such as Grave's ophthalmopathy.
Methods: We stained archival jejunal biopsies from 5 children with CD at diagnosis, on gluten-free diet and challenge for sulphated GAGs.
Background. The incidence of inflammatory bowel disease (IBD) is increasing in the paediatric population. Since 2007, a single surgeon whose main practice is in the treatment of adults has performed surgery for IBD in adults and children within two dedicated multidisciplinary teams.
View Article and Find Full Text PDFObjectives: Allergic colitis shows overlap with classic inflammatory bowel disease (IBD). Clinically, allergic colitis is associated with dysmotility and abdominal pain, and mucosal eosinophilia is characteristic. We thus aimed to characterise mucosal changes in children with allergic colitis compared with normal tissue and classic IBD, focusing on potential interaction between eosinophils and mast cells with enteric neurones.
View Article and Find Full Text PDFObjective: The aetiology of necrotising enterocolitis (NEC) is unknown, but luminal factors and epithelial leakiness appear critical triggers of an inflammatory cascade. A separate finding has been suggested in mouse models, in which disruption of glial cells in the myenteric plexus induced a severe NEC-like lesion. We have thus looked for evidence of neuroglial abnormality in NEC.
View Article and Find Full Text PDFIntroduction: Single port laparoscopic surgery has been increasingly used for complex surgical procedures. To our knowledge, this is the first published report of a single port laparoscopic subtotal colectomy and ileostomy in an adolescent patient with ulcerative colitis.
Case Report: A 13-year old female patient with ulcerative colitis resistant to maximal medical therapy underwent a single port laparoscopic subtotal colectomy and ileostomy.
Background: Enterotoxin-producing Staphylococcus aureus may cause severe inflammatory intestinal disease, particularly in infants or immunodeficient or elderly patients. They are also recognized to be associated with sudden infant death syndrome. Little is known, however, about mucosal responses to staphylococci.
View Article and Find Full Text PDFAim: To assess feasibility of a finger prick-based kit as method for self-testing of first and second-degree relatives of coeliac disease (CD) patients.
Methods: A total number of 379 subjects were invited to participate in this study, consisting of 197 first-degree and 182 second-degree relatives of CD patients. The self-testing kit (Biocard™) was sent out with included instructions for use.
Background: Human beta-defensins (hBDs) are antimicrobial peptides known to play a major role in intestinal innate host defence. Altered mucosal expression of hBDs has been suggested to be implicated in chronic inflammatory bowel disease pathogenesis. However, little is known about expression of these peptides in children.
View Article and Find Full Text PDFJ Pediatr Gastroenterol Nutr
August 2009
Objectives: Although it is a well-described syndrome in infants, eosinophilic colitis is a loosely defined and poorly understood diagnosis in older children. The aims of this case series were to characterise colonic eosinophilia in children and to determine whether it represents a distinct clinicopathological condition.
Methods: We retrospectively reviewed symptomatic children older than 12 months with the principal diagnosis of colonic eosinophilia who presented between January 2000 and February 2007 (n = 38) and a further 10 children whose colonic biopsies were reported as histologically normal.
Background: Kwashiorkor, a form of severe malnutrition with high mortality, is characterized by edema and systemic abnormalities. Although extremely common, its pathophysiology remains poorly understood, and its characteristic physical signs are unexplained.
Objective: Because kwashiorkor can develop in protein-losing enteropathy, which is caused by a loss of enterocyte heparan sulfate proteoglycan (HSPG), and previous observations suggest abnormal sulfated glycosaminoglycan (GAG) metabolism, we examined whether intestinal GAG and HSPG are abnormal in children with kwashiorkor.
Background: Mutations in alpha6 or beta4 integrins (ITGA6, ITGB4) are known to cause junctional epidermolysis bullosa with pyloric atresia (JEB-PA), often lethal in infancy through skin desquamation. There is 1 report of pyloric atresia associated with a desquamatory enteropathy but without skin disease, of unknown molecular basis.
Patients And Methods: We report 2 Kuwaiti siblings with pyloric atresia and life-threatening intestinal desquamation without significant skin abnormality.
Typical enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) employ either Nck, TccP/TccP2, or Nck and TccP/TccP2 pathways to activate the neuronal Wiskott-Aldrich syndrome protein (N-WASP) and to trigger actin polymerization in cultured cells. This phenotype is used as a marker for the pathogenic potential of EPEC and EHEC strains.
View Article and Find Full Text PDFEnterohaemorrhagic Escherichia coli (EHEC) are an important cause of diarrhoeal and renal disease in man. Studies of a single prototypic O157 : H7 strain have shown tropism for follicle-associated epithelium (FAE) of distal ileal Peyer's patches without colonization of either small or large intestine. This study determined tropism in a range of Shiga toxin (Stx)-negative EHEC strains and looked for factors that might induce colonic colonization using human in vitro intestinal organ culture (IVOC).
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