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Aim: To determine the relationship between blood tests and oesophageal histology in Eosinophilic oesophagitis (EoE). Methods: All children diagnosed with EoE at one hospital from 2000 to 2009 were considered for inclusion in this study. Three blood test results were analysed, blood eosinophil count, serum total immunoglobulin E (IgE) and radioallergosorbent tests (RAST) to common food allergens. Oesophageal histology was prospectively re-reviewed, and mean eosinophil counts were enumerated. Blood test results were correlated with oesophageal eosinophil counts using Spearman's rank test. Results: Forty children (70% boys) were included in this study, median age at diagnosis 6.5 years (range 0-15). At the time of diagnosis, 78% of children had a raised blood eosinophil count, 90% had a raised serum total IgE and 83% had one or more positive RAST tests. The mean oesophageal eosinophil count was significantly correlated with both blood eosinophil count (p = 0.008) and serum total IgE level (p = 0.008). Conclusion: This study shows that blood tests are often abnormal in children with EoE at the time of diagnosis. Our data demonstrate an association between histological abnormalities and blood test results in children with EoE. [ABSTRACT FROM AUTHOR]

Aim: To assess self-reported Quality of life (QoL) in children with Gastro-oesophageal reflux disease (GORD) aged 5–18 and compare this with both disease and healthy control children in a prospective consecutive sample. Methods: All children attending a tertiary paediatric gastroenterology clinic from February 2009 to May 2009 with GORD, chronic constipation and inflammatory bowel disease (IBD) were asked to complete the validated PedsQL generic QoL assessment (self-report) at their clinic appointment. The PedsQL considers physical, emotional, social and school domains and is scored from 0 to 100. Healthy children were also recruited from the same site. Groups were compared using the independent samples Student’s t-test. Results: A total of 184 children completed the assessment [103 (56%) male, mean age 10.7 years ± 3.3] including 40 children with GORD, 44 with chronic constipation, 59 with IBD and 41 healthy children. QoL was significantly lower in the GORD group compared with both children with IBD (74 vs. 82) and healthy children (74 vs. 84), and was comparable to that of children with chronic constipation (74 vs. 74). Conclusions: Self-reported QoL in children with GORD attending a tertiary paediatric gastroenterology clinic is significantly reduced compared with both healthy children and children with IBD. [ABSTRACT FROM AUTHOR]

Background: The gastrointestinal microbiota has an important role in mucosal immune homoeostasis and may contribute to maintaining mucosal healing in Crohn's disease (CD)., Aim: To identify changes in the microbiota, metabolome and protease activity associated with mucosal healing in established paediatric CD METHODS: Twenty-five participants aged 3-18 years with CD, disease duration of over 6 months, and maintenance treatment with biological therapy were recruited. They were divided into a low calprotectin group (faecal calprotectin <100 μg/g, "mucosal healing," n = 11), and a high calprotectin group (faecal calprotectin >100 μg/g, "mucosal inflammation," n = 11). 16S gene-based metataxonomics, 1 H-NMR spectroscopy-based metabolic profiling and protease activity assays were performed on stool samples., Results: Relative abundance of Dialister species was six-times greater in the low calprotectin group (q = 0.00999). Alpha and beta diversity, total protease activity and inferred metagenomic profiles did not differ between groups. Pentanoate (valerate) and lysine were principal discriminators in a machine-learning model which differentiated high and low calprotectin samples using NMR spectra (R 2 0.87, Q 2 0.41). Mean relative concentration of pentanoate was 1.35-times greater in the low calprotectin group (95% CI 1.03-1.68, P = 0.036) and was positively correlated with Dialister. Mean relative concentration of lysine was 1.54-times greater in the high calprotectin group (95% CI 1.05-2.03, P = 0.028)., Conclusions: This multiomic study identified an increase in Dialister species and pentanoate, and a decrease in lysine, in patients with "mucosal healing." It supports further investigation of these as potential novel therapeutic targets in CD., (© 2020 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Objective: To systematically review the evidence base for the medical (pharmaceutical and nutritional) treatment of paediatric inflammatory bowel disease., Methods: Key clinical questions were formulated regarding different treatment modalities used in the treatment of paediatric (not adult-onset) IBD, in particular the induction and maintenance of remission in Crohn disease and ulcerative colitis. Electronic searches were performed from January 1966 to December 2006, using the electronic search strategy of the Cochrane IBD group. Details of papers were entered on a dedicated database, reviewed in abstract form, and disseminated in full for appraisal. Clinical guidelines were appraised using the AGREE instrument and all other relevant papers were appraised using Scottish Intercollegiate Guidelines Network methodology, with evidence levels given to all papers., Results: A total of 6285 papers were identified, of which 1255 involved children; these were entered on the database. After critical appraisal, only 103 publications met our criteria as evidence on medical treatment of paediatric IBD. We identified 3 clinical guidelines, 1 systematic review, and 16 randomised controlled trials; all were of variable quality, with none getting the highest methodological scores., Conclusions: This is the first comprehensive review of the evidence base for the treatment of paediatric IBD, highlighting the paucity of trials of high methodological quality. As a result, the development of clinical guidelines for managing children and young people with IBD must be consensus based, informed by the best-available evidence from the paediatric literature and high-quality data from the adult IBD literature, together with the clinical expertise and multidisciplinary experience of paediatric IBD experts.

The occurrence in the neonatal period and into early infancy of two inflammatory conditions, necrotising enterocolitis (NEC), and allergic colitis, that do not occur in later life highlight the peculiar vulnerability of the gastrointestinal tract in the newborn period to otherwise innocuous insults. The pathogenesis of the relatively benign allergic colitis as a mucosal inflammatory process driven by dietary antigens is relatively well characterised, and its treatment with dietary manipulation is well established. For NEC, hypoxic/ischaemic insult, mucosal immaturity, and its interaction with the intestinal microflora are understood to be the main factors in pathogenesis. Thus far, the most productive interventions have been in preventative approaches, in particular feeding strategies, to reduce the incidence of the condition whilst establishing adequate growth and progression onto enteral feeding. For established NEC, supportive medical therapy or surgical intervention remains the mainstay or treatment, although novel therapies, such as platelet-activating factor (PAF) inhibitors and epidermal growth factor (EGF), have shown some promise in animal models of the condition.

We have been able to show that CT3211 is an effective oral treatment in children with active Crohn's disease. It was well tolerated, and there were minimal side effects. At the mucosal site of disease there was macroscopic and histological improvement, together with evidence of downregulation of the pro-inflammatory cytokines IL-1 beta, IL-8, and IFN-gamma.

Anti-TNF-alpha Ab therapy has been shown to be of benefit in the treatment of active Crohn's disease, but the tissue-injuring processes in the gut mediated by TNF-alpha that might be inhibited by neutralizing Ab are unknown. In this work, we have used a p55 TNF receptor-human IgG fusion protein (TNFR-IgG) to prevent the severe mucosal injury that ensues when lamina propria T cells in explant cultures of human fetal small intestine are directly activated with the lectin PWM. Following T cell activation and associated with mucosal injury, there is a marked elevation of soluble TNF-alpha in organ culture supernatants and a large increase in TNF-alpha mRNA transcripts. The addition of TNFR-IgG at the onset of cultures greatly reduced PWM-induced tissue injury, without inhibiting the increase in TNF-alpha and IFN-gamma transcripts seen following T cell activation. Mucosal injury in this model is mediated by endogenously-produced matrix metalloproteinases (MMPs). When TNFR-IgG was added to PWM-stimulated explants, there was a reduction in MMPs in the explant culture supernatants, especially stromelysin-1. Recombinant TNF-alpha and IL-1beta added directly to mucosal mesenchymal cell lines also caused an increase in MMP production, but only the former was inhibited by the TNFR-IgG. These results suggest that one of the ways in which TNF-alpha causes tissue injury in the gut is by stimulating mucosal mesenchymal cell to secrete matrix-degrading metalloproteinases. Neutralization of this activity should help maintain tissue integrity.