Enteropathic spondyloarthropathy:A common genetic background with inflammatory bowel disease?

The association between spondyloarthropathy and in flammatory bowel disease(IBD) is largely established, although prevalence is variable because of different population selection and diagnostic methodologies.Most studies indicate that as many as 10%15% of cases of IBD are complicated by ankylosing spondylitis(AS) or other forms of spondylarthritis(SpA).Of note, ileal inflammation resembling IBD has been reported in up to two thirds of cases of SpA, and it has been suggested that the presence of ileitis is associated with the chronic ity of articular complications.Although this observation is of interest to unravel the pathophysiology of the disease, systematic screening of patients with SpA by ileocolonos copy is not indicated in the absence of gut symptoms, as only a small proportion of patients with subclinical gut inflammation will develop overt IBD over time.The existence of familial clustering of both IBD and AS, the coexistence of both conditions in a patient, the evidence of an increased risk ratio among f irstand seconddegree relatives of affected AS or IBD patients and f inally, the increased crossrisk ratios between AS and IBD, strongly suggest a shared genetic background.So far, however, IL23R is the only identified susceptibility gene shared by both IBD and AS.Although functional studies are still needed to better understand its pathogenic role, great ef fort is being spent therapeutically targeting this pathway that may prove effective for both disorders.

Replication of interleukin 23 receptor and autophagy-related 16-like 1 association in adult-and pediatric-onset inflammatory bowel disease in Italy

AIM: To investigate gene variants in a large Italian inflammatory bowel disease (IBD) cohort, and to analyze the correlation of sub-phenotypes (including age at diagnosis) and epistatic interaction with other IBD genes. METHODS: Total of 763 patients with Crohn's disease (CD, 189 diagnosed at age < 19 years), 843 with ulcerative colitis (UC, 179 diagnosed <19 years), 749 healthy controls, and 546 healthy parents (273 trios) were included in the study. The rs2241880 [autophagy-related 16-like 1 (ATG16L1)], rs11209026 and rs7517847 [interleukin 23 receptor (IL23R)], rs2066844, rs2066845, rs2066847 (CARD15), rs1050152 (OCTN1), and rs2631367 (OCTN2) gene variants were genotyped. RESULTS: The frequency of G allele of ATG16L1 SNP (Ala197Thr) was increased in patients with CD compared with controls (59% vs 54% respectively) (OR = 1.25, CI = 1.08-1.45, P = 0.003), but not in UC (55%). The frequency of A and G (minor) alleles of Arg381Gln, rs11209026 and rs7517847 variants of IL23R were reduced significantly in CD (4%, OR = 0.62, CI = 0.45-0.87, P = 0.005; 28%, OR = 0.64, CI = 0.55-0.75, P < 0.01), compared with controls (6% and 38%, respectively). The A allele (but not G) was also reduced signifi cantly in UC (4%, OR = 0.69, CI = 0.5-0.94, P = 0.019). No association was demonstrated with sub-phenotypes and interaction with CARD15 , and OCTN1/2 genes, although both gene variants were associated with pediatric-onset disease. CONCLUSION: The present study confirms the association of IL23R polymorphisms with IBD, and ATG16L1 with CD, in both adult- and pediatric-onset subsets in our study population.

How evidence-based are current guidelines for managing patients with peptic ulcer bleeding?

Current guidelines for managing ulcer bleeding state that patients with major stigmata should be managed by dual endoscopic therapy(injection with epinephrine plus a thermal or mechanical modality) followed by a high dose intravenous infusion of proton pump inhibitors(PPIs).This paper aims to review and critically evaluate evidence supporting the purported superiority of a continuous infusion over less intensive regimens of PPIs administration and the need for adding a second hemostatic endoscopic procedure to epinephrine injection.Systematic searches of PubMed,EMBASE and the Cochrane library were performed.There is strong evidence for an incremental benefit of PPIs over H2receptor antagonists or placebo for the outcome of patients with peptic ulcer bleeding following endoscopic hemostasis.However,the benefit of PPIs is unrelated to either the dosage(intensive vs standard regimen) or the route of administration(intravenous vs oral).There is significant heterogeneity among the 15 studies that compared epinephrine with epinephrine plus a second modality,which might preclude the validity of reported summary estimates.Studies without second look endoscopy plus re-treatment of re-bleeding lesions showed a signif icant benef it of adding a second endoscopic modality for hemostasis,while studies with second-look and re-treatment showed equal efficacy between endoscopic mono and dual therapy.Inconclusive experimental evidence supports the current recommendation of the use of dual endoscopic hemostatic means and infusion of high-dose PPIs as standard therapy for patients with bleeding peptic ulcers.Presently,the combination of epinephrine monotherapy with standard doses of PPIs constitutes an appropriate treatment for the majority of patients.

Clinical and economic impact of infliximab one-hour infusion protocol in patients with inflammatory bowel diseases:A multicenter study

AIM To assess the impact of short infliximab(IFX) infusion on hospital resource utilization and costs.METHODS All inflammatory bowel diseases(IBD) patients who received IFX 1 h infusion from March 2007 to September 2014 in eight centers from Southern Italy were included in the analysis. Demographic, clinical and infusion related data were collected. The potential benefits related to the short infusion protocol were assessed both in terms of time saving and increased infusion unit capacity. In addition, indirect patient-related cost savings were evaluated.RESULTS One hundred and twenty-five patients were recruited(64 with ulcerative colitis and 61 with Crohn's disease). Median duration of disease was of 53 mo and mean age of pts at diagnosis was of 34 years(SD: ± 13). Adverse infusion reactions were reported in less than 4% both before and after short infusion. The total number of infusions across the selected centers was of 2501(30.5% short infusions). In the analyzed cohort, 1143 h were saved(762 in the infusion and 381 in observation phases) through the rapid IFX infusion protocol. This time saving(-15% compared to the standard protocol in infusion phase) represents, from the hospital perspective, an opportunity to optimize infusion unit capacity by allocating the saved time in alternative cost-effective treatments. This is the case of opportunity cost that represents the value of forgone benefit which could be obtained from a resource in its next-best alternative use. Hence, an extra hour of infusion in the case of standard 2-h IFX represents a loss in opportunity to provide other cost effective services. The analysis showed that the short infusion increased the infusion units capacity up to 50% on days when the IFX infusions were scheduled(infusion phase). Furthermore, the analysis showed that the short IFX infusion protocol leads to time savings also in the post-infusion phase(observation) leading to a time saving of 10% on average among the analyzed centers. Finally, the short infusion protocol has been demonstrated to lead to indirect cost savings of €138/patient(average-€17.300 on the whole cohort).CONCLUSION A short IFX infusion protocol can be considered time and cost saving in comparison to the standard infusion protocol both from the hospital's perspective, as it contributes to increase infusion units capacity, and the patients' perspective, as it reduces indirect costs and the impact of treatment on everyday life and work productivity.