Faecal calprotectin effectively excludes inflammatory bowel disease in 789 symptomatic young adults with/without alarm symptoms: a prospective UK primary care cohort study.

BACKGROUND: Primary care faecal calprotectin testing distinguishes inflammatory bowel disease (IBD) from functional gut disorder in young patients presenting with abdominal symptoms; however, previous evaluations have excluded patients with alarm symptoms. AIMS: We sought to evaluate the diagnostic accuracy of calprotectin to distinguish IBD from functional gut disorder in young adults in whom general practitioners (GPs) suspected IBD; including patients reporting gastrointestinal alarm symptoms. We hypothesised that calprotectin would reduce secondary care referrals and healthcare costs. METHODS: We undertook a prospective cohort study of 789 young adults (18-46 years old) presenting with gastrointestinal symptoms to 49 local general practices that had undergone calprotectin testing (1053 tests: between Jan 2014 and May 2016) because of suspected IBD. We considered calprotectin levels of ≥100 µg/g positive. Primary and secondary care records over 12 months from the point of calprotectin testing were used as the reference standard. RESULTS: Overall, 39% (308/789) patients reported gastrointestinal alarm symptoms and 6% (50/789) tested patients were diagnosed with IBD. The positive and negative predictive values of calprotectin testing for distinguishing IBD from functional gut disorder in patients with gastrointestinal alarm symptoms were 50% (95% CI 36%-64%) and 98% (96%-100%): and in patients without gastrointestinal alarm symptoms were 27% (16%-41%) and 99% (98%-100%), respectively. We estimate savings of 279 referrals and £160 per patient. CONCLUSIONS: Calprotectin testing of young adults with suspected IBD in primary care accurately distinguishes IBD from functional gut disorder, even in patients with gastrointestinal alarm symptoms and reduces secondary care referrals and diagnostic healthcare costs.

Exclusive enteral nutrition provides an effective bridge to safer interval elective surgery for adults with Crohn's disease.

BACKGROUND: Few studies have reported the systematic use of exclusive enteral nutrition in the perioperative setting. AIM: To test the hypothesis that exclusive enteral nutrition provides a safe and effective bridge to surgery and reduces post-operative complications, in adult patients with Crohn's disease requiring urgent surgery for stricturing or penetrating complications. METHODS: Patients treated with exclusive enteral nutrition prior to surgery were each matched with two control patients for disease behaviour, type of surgery, age at diagnosis and disease duration. Data on disease phenotype, nutritional status, operative course and post-operative complications were obtained. RESULTS: Twenty-five per cent [13/51] patients treated with exclusive enteral nutrition avoided surgery. Exclusive enteral nutrition had no effect on pre-operative weight, but it significantly reduced serum CRP [median at baseline 36 (interquartile range, IQR: 13-91] vs. pre-operation 8 (4-31) mg/L, P = 0.02]. The median (IQR) length of surgery was shorter in patients pre-optimised with exclusive enteral nutrition than controls [3.0 (2.5-3.5) vs. 3.5 (3.0-4.0) hours respectively, P < 0.001]. Multivariable logistic regression analysis confirmed that going straight-to-surgery compared exclusive enteral nutrition pre-optimisation was associated with a ninefold increase in the incidence of post-operative abscess and/or anastomotic leak [OR 9.1; 95% CI (1.2-71.2), P = 0.04]. CONCLUSIONS: Exclusive enteral nutrition frequently down-stages the need for surgery in patients presenting with stricturing or penetrating complications of Crohn's disease; it is associated with a reduction in systemic inflammation, operative times and the incidence of post-operative abscess or anastomotic leak. Further trials are needed to elucidate how exclusive enteral nutrition may improve operative outcomes.

Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling.

OBJECTIVE: Our previous coeliac disease genome-wide association study (GWAS) implicated risk variants in the human leucocyte antigen (HLA) region and eight novel risk regions. To identify more coeliac disease loci, we selected 458 single nucleotide polymorphisms (SNPs) that showed more modest association in the GWAS for genotyping and analysis in four independent cohorts. DESIGN: 458 SNPs were assayed in 1682 cases and 3258 controls from three populations (UK, Irish and Dutch). We combined the results with the original GWAS cohort (767 UK cases and 1422 controls); six SNPs showed association with p<1 x 10(-04) and were then genotyped in an independent Italian coeliac cohort (538 cases and 593 controls). RESULTS: We identified two novel coeliac disease risk regions: 6q23.3 (OLIG3-TNFAIP3) and 2p16.1 (REL), both of which reached genome-wide significance in the combined analysis of all 2987 cases and 5273 controls (rs2327832 p = 1.3 x 10(-08), and rs842647 p = 5.2 x 10(-07)). We investigated the expression of these genes in the RNA isolated from biopsies and from whole blood RNA. We did not observe any changes in gene expression, nor in the correlation of genotype with gene expression. CONCLUSIONS: Both TNFAIP3 (A20, at the protein level) and REL are key mediators in the nuclear factor kappa B (NF-kappaB) inflammatory signalling pathway. For the first time, a role for primary heritable variation in this important biological pathway predisposing to coeliac disease has been identified. Currently, the HLA risk factors and the 10 established non-HLA risk factors explain approximately 40% of the heritability of coeliac disease.