Delivering optimal care for inflammatory bowel disease patients in Scotland in 2014

The inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis, present an ever increasing burden to the healthcare systems in the Western world. Scotland in particular has seen a significant increase in both diseases, particularly Crohn's disease. It is thus of paramount importance that secondary care services within Scotland are equipped to cope with this increased demand at a time when the treatment options are broadening, patients expectations are increasing and healthcare budgets face major restriction. This article outlines some aspects of optimal delivery of an IBD service in secondary care

Long-term follow-up of endoscopic histoacryl glue injection for the management of gastric variceal bleeding

Background: Variceal bleeding is an acute medical emergency with high mortality. Although less common than oesophageal variceal haemorrhage, gastric variceal bleeding is more severe and more difficult to control. The optimal therapy for gastric variceal bleeding remains unclear although endoscopic injection of N-Butyl-2-Cyanoacrylate (Histoacryl) glue is often used. However, its long-term efficacy is poorly described. We studied the immediate and long-term effects of Histoacryl glue injection as treatment for bleeding gastric varices in a large UK hospital. Method: Endoscopy records and case notes were used to identify patients receiving Histoacryl injection for gastric variceal bleeding over a 4-year period. Results: Thirty-one patients received Histoacryl for gastric variceal bleeding. Seventy-four per cent patients had alcohol-related liver disease and 61% of cirrhotics were Childs Pugh grade B or C. Fifty-eight per cent were actively bleeding during the procedure with 100% haemostasis rates achieved. Two patients developed pyrexia within 24 h of injection settling with antibiotics. No other complications were encountered. Mean overall follow-up was 35 months, with mean follow-up of survivors 57 months. Forty-eight per cent patients had endoscopic ultrasound assessment of varices during follow-up with no effect on rebleeding rates. Thirteen per cent required subsequent transjugular intrahepatic portosystemic shunt placement. Gastric variceal rebleeding rate was 10% at 1 year and 16% in total. One- and two-year mortality was 23% and 35%, respectively. Conclusion: Endoscopic injection of Histoacryl glue appears to be a safe and effective treatment for gastric variceal bleeding. Further data are required to compare it with other therapies in this situation

Faecal calprotectin in the assessment of Crohn's disease activity

Background: Clinical and laboratory assessment of activity in Crohn's disease (CD) correlate poorly with endoscopic findings. Calprotectin is a calcium-binding protein abundant in neutrophil cytosol, and extremely stable in faeces. Faecal calprotectin (FC) is an excellent surrogate marker of neutrophil influx into the bowel lumen. Aim: To assess whether FC concentration from a spot stool sample reliably detects active inflammation in patients with CD. Design: Cross-sectional comparative study. Methods: Subjects had a previously confirmed diagnosis of CD and were suspected on clinical grounds to be in the midst of a relapse. Thirty-five entered the study; they underwent radiolabelled white cell scanning (WCS) and had a stool sample collected for calprotectin measurement on the same day. A Crohn's disease activity index (CDAI) was also calculated for each. The WCS scans were scored at six standard sites to give a mean total, ‘extent‘, ‘severity’ and ‘combined extent and severity’ scores. Results: FC was significantly and positively correlated with mean total (r = 0.73, p<0.001), ‘extent’ (r = 0.71, p<0.001), ‘severity’ (r = 0.64, p<0.001) and combined ‘extent and severity’ WCS scores (r = 0.71, p<0.001). A cut-off of faecal calprotectin >100 µg/g gave a sensitivity of 80%, specificity of 67%, positive predictive value of 87% and a negative predictive value of 64% in identifying those with and without any inflammation on WCS. There was, however, no significant correlation between CDAI and mean total WCS score (r = 0.21, p = 0.24), nor between CDAI and FC (r = 0.33, p = 0.06). Discussion: While the CDAI does not accurately reflect inflammatory activity in CD, a one-off FC reliably detects the presence or absence of intestinal inflammation in adult patients with CD, compared to WCS

Outpatient management of patients with low-risk upper-gastrointestinal haemorrhage: multicentre validation and prospective evaluation

Background: Upper-gastrointestinal haemorrhage is a frequent reason for hospital admission. Although most risk scoring systems for this disorder incorporate endoscopic findings, the Glasgow-Blatchford bleeding score (GBS) is based on simple clinical and laboratory variables; a score of 0 identifies low-risk patients who might be suitable for outpatient management. We aimed to evaluate the GBS then assess the effect of a protocol based on this score for non-admission of low-risk individuals. Methods: Our study was undertaken at four hospitals in the UK. We calculated GBS and admission (pre-endoscopy) and full (post-endoscopy) Rockall scores for consecutive patients presenting with upper-gastrointestinal haemorrhage. With receiver-operating characteristic (ROC) curves, we compared the ability of these scores to predict either need for clinical intervention or death. We then prospectively assessed at two hospitals the introduction of GBS scoring to avoid admission of low-risk patients. Findings: Of 676 people presenting with upper-gastrointestinal haemorrhage, we identified 105 (16%) who scored 0 on the GBS. For prediction of need for intervention or death, GBS (area under ROC curve 0·90 [95% CI 0·88–0·93]) was superior to full Rockall score (0·81 [0·77–0·84]), which in turn was better than the admission Rockall score (0·70 [0·65–0·75]). When introduced into clinical practice, 123 patients (22%) with upper-gastrointestinal haemorrhage were classified as low risk, of whom 84 (68%) were managed as outpatients without adverse events. The proportion of individuals with this condition admitted to hospital also fell (96% to 71%, p<0·00001). Interpretation: The GBS identifies many patients presenting to general hospitals with upper-gastrointestinal haemorrhage who can be managed safely as outpatients. This score reduces admissions for this condition, allowing more appropriate use of in-patient resources

P014 Identification of Crohn’s Disease Immunopathotypes

Background: Crohn’s disease (CD) is a chronic inflammatory gastrointestinal condition, with globally increasing incidence. Patients with CD suffer from a loss of tolerance towards their commensal microbiota causing an aberrant immune response, occurring in a protracted relapse and remission cycle. Although a variety of frontline therapies is currently available, including targeted therapies such as biologic drugs, 30–40% of CD patients still require surgery to manage the disease. At present, the immunobiology of CD is not fully understood. However, differences in immune responses between patients might play an important role in diverse treatment responses. The aim of this study was to identify differences in peripheral and local immune responses of CD to understand differences in disease behaviour and treatment outcome. Methods: Peripheral blood mononuclear cells and plasma were isolated from whole blood of a cross-sectional CD patient cohort (nCD = 12) and normal controls (NC, nNC = 28). Flow cytometry analysis and multiplex assays were used to quantify immune cell populations and cytokine levels, respectively. The local immune response was analysed by bulk RNA sequencing of mucosal colonic biopsies either from inflamed CD or normal tissue. Gene signatures were then followed up by validation in publicly deposited gene expression datasets (nCD = 36, nNC = 24), and by measurement of specific proteins using our archived samples. Results: Peripheral immunophenotyping of the initial cross-sectional study displayed three different types of CD patients, characterised by either a decrease in leukocyte populations, an increase of cytokines, or a change in both. Analysis of the RNAseq data derived from colonic biopsies revealed four distinct clusters in genes associated with the immune response in CD patients. Further pathway analysis showed one cluster with an enriched B cell signature and another cluster with an elevated macrophage and neutrophil response. We utilised publicly available gene expression datasets to validate these signatures in a larger cohort and identified a selection of patients with an up-regulated pro-inflammatory macrophage response. Using correlation analysis, we suggest an immunopathotype with increased macrophage activation which is potentially associated with a more severe form of the disease. Conclusion: We have identified distinct immunopathotypes in both the peripheral and local immune response of CD patients. Further investigation will correlate these distinct immune responses in CD with clinical parameters, to understand associations between diverse treatment responses and disease behaviours

Multicentre comparison of the Glasgow Blatchford and Rockall scores in the prediction of clinical end-points after upper gastrointestinal haemorrhage

Background: The Glasgow Blatchford Score (GBS) is increasingly being used to predict intervention and outcome following upper gastrointestinal haemorrhage (UGIH). Aim: To compare the GBS with both the admission and full Rockall scores in predicting specific clinical end‐points following UGIH. Patients and methods: Data on consecutive patients presenting to four UK hospitals were collected. Admission history, clinical and laboratory data, endoscopic findings, treatment and clinical follow‐up were recorded. Using ROC curves, we compared the three scores in the prediction of death, endoscopic or surgical intervention and transfusion. Results: A total of 1555 patients (mean age 56.7 years) presented with UGIH during the study period. Seventy‐four (4.8%) died, 223 (14.3%) had endoscopic or surgical intervention and 363 (23.3%) required transfusion. The GBS was similar at predicting death compared with both the admission Rockall (area under ROC curve 0.804 vs. 0.801) and full Rockall score (AUROC 0.741 vs. 0.790). In predicting endo‐surgical intervention, the GBS was superior to the admission Rockall (AUROC 0.858 vs. 0.705; P < 0.00005) and similar to the full Rockall score (AUROC 0.822 vs. 0.797). The GBS was superior to both admission Rockall (AUROC 0.944 vs. 0.756; P < 0.00005) and full Rockall scores (AUROC 0.935 vs. 0.792; P < 0.00005) in predicting need for transfusion. Conclusions: Despite not incorporating age, the GBS is as effective as the admission and full Rockall scores in predicting death after UGIH. It is superior to both the admission and full Rockall scores in predicting need for transfusion, and superior to the admission Rockall score in predicting endoscopic or surgical intervention