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Second European evidence-based consensus on the prevention, diagnosis and management of opportunistic infections in inflammatory bowel disease

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Genome-wide association studies and follow-up meta-analyses in Crohn's disease (CD) and ulcerative colitis (UC) have recently identified 163 disease-associated loci that meet genome-wide significance for these two inflammatory bowel diseases (IBD). These discoveries have already had a tremendous impact on our understanding of the genetic architecture of these diseases and have directed functional studies that have revealed some of the biological functions that are important to IBD (e.g. autophagy). Nonetheless, these loci can only explain a small proportion of disease variance (~14% in CD and 7.5% in UC), suggesting that not only are additional loci to be found but that the known loci may contain high effect rare risk variants that have gone undetected by GWAS. To test this, we have used a targeted sequencing approach in 200 UC cases and 150 healthy controls (HC), all of French Canadian descent, to study 55 genes in regions associated with UC. We performed follow-up genotyping of 42 rare non-synonymous variants in independent case-control cohorts (totaling 14,435 UC cases and 20,204 HC). Our results confirmed significant association to rare non-synonymous coding variants in both IL23R and CARD9, previously identified from sequencing of CD loci, as well as identified a novel association in RNF186. With the exception of CARD9 (OR = 0.39), the rare non-synonymous variants identified were of moderate effect (OR = 1.49 for RNF186 and OR = 0.79 for IL23R). RNF186 encodes a protein with a RING domain having predicted E3 ubiquitin-protein ligase activity and two transmembrane domains. Importantly, the disease-coding variant is located in the ubiquitin ligase domain. Finally, our results suggest that rare variants in genes identified by genome-wide association in UC are unlikely to contribute significantly to the overall variance for the disease. Rather, these are expected to help focus functional studies of the corresponding disease loci. © 2013 Beaudoin et al.

Genome-wide association studies and follow-up meta-analyses in Crohn's disease (CD) and ulcerative colitis (UC) have recently identified 163 disease-associated loci that meet genome-wide significance for these two inflammatory bowel diseases (IBD). These discoveries have already had a tremendous impact on our understanding of the genetic architecture of these diseases and have directed functional studies that have revealed some of the biological functions that are important to IBD (e.g. autophagy). Nonetheless, these loci can only explain a small proportion of disease variance (~14% in CD and 7.5% in UC), suggesting that not only are additional loci to be found but that the known loci may contain high effect rare risk variants that have gone undetected by GWAS. To test this, we have used a targeted sequencing approach in 200 UC cases and 150 healthy controls (HC), all of French Canadian descent, to study 55 genes in regions associated with UC. We performed follow-up genotyping of 42 rare non-synonymous variants in independent case-control cohorts (totaling 14,435 UC cases and 20,204 HC). Our results confirmed significant association to rare non-synonymous coding variants in both IL23R and CARD9, previously identified from sequencing of CD loci, as well as identified a novel association in RNF186. With the exception of CARD9 (OR = 0.39), the rare non-synonymous variants identified were of moderate effect (OR = 1.49 for RNF186 and OR = 0.79 for IL23R). RNF186 encodes a protein with a RING domain having predicted E3 ubiquitin-protein ligase activity and two transmembrane domains. Importantly, the disease-coding variant is located in the ubiquitin ligase domain. Finally, our results suggest that rare variants in genes identified by genome-wide association in UC are unlikely to contribute significantly to the overall variance for the disease. Rather, these are expected to help focus functional studies of the corresponding disease loci. © 2013 Beaudoin et al.

M Cottone, V CriscuoliBiomedical Department of Internal and Specialist Medicine, Division of Medicine, Villa Sofia-V Cervello Hospital, Palermo University, Palermo, ItalyAbstract: Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract characterized by recurring flares followed by periods of inactive disease and remission. The etiology is unknown, although the common opinion is that the disease arises from a disordered immune response to the gut contents in genetically predisposed individuals. Infliximab (IFX), a chimeric immunoglobulin G1 monoclonal antibody to tumor necrosis factor, has dramatically changed the approach to managing patients with CD and improving their treatment, by achieving treatment goals, such as mucosal healing, and decreasing the need for hospitalizations and surgeries. This review provides an update on existing evidence for the use of IFX in CD, taking into account the safety profile in clinical practice and special situations such as pregnancy. Antitumor necrosis factor therapy has been evaluated as an induction and maintenance therapy in CD in several randomized controlled trials and meta-analyses, showing efficacy in both clinical settings. Early use of biologics may improve patient outcomes in active CD. However, a widespread use of a “top-down” approach in all CD patients cannot be recommended. Clinical factors at diagnosis may predict poor outcome in CD, and should be taken into account when determining the initial therapeutic approach.Keywords: Crohn’s disease, infliximab, adult

Data on management and long-term follow-up of Helicobacter pylori-associated MALT-lymphoma in clinical practice are scanty. We evaluate the long-term efficacy of H. pylori eradication on low-grade MALT-lymphoma, and the efficacy of further therapies in refractory patients.

The legislation regarding marine pollution caused by ships has been developed on several regulatory levels (international, european and national) and has frequently been fragmented and heterogeneous, creating problems of application and harmonisation of the subject. The Marpol Convention 73/78, still remains the most important international ruling in force with regard to marine pollution caused by ships. In the course of the struggle against biological marine pollution, the international community adopted, on 13 th February 2004, the International Convention for the Control and Management of Ship's Ballast Water and sediments, which is not currently in force. On a national level, there exists the law of 8th February 2006, no. 61, which foresees the institution of ecological protected areas beyond the outer national sea limits; in these areas, the state of Italy will be able to oblige foreign ships to respect the increased safety standards (see law no. 979/82, art. 16, 17 e 20) in order to safeguard the marine environment

Although the stomach is the most frequent site of intestinal lymphomas, few data are available on both clinical endoscopic presentation of gastric lymphoma and possible differences between low-grade and high-grade lymphomas.

In the literature there are indications of associations between health-related quality of life (HRQoL) in inflammatory bowel disease and disease activity, psychological status, coping, stressful life events, and social support. The aim of this study was to examine whether a relation exists between quality of health care and HRQoL, taking possible confounding variables into account. For this purpose, one single questionnaire was compiled from existing validated questionnaires. A population-based inception cohort of 1056 patients with inflammatory bowel disease in eight countries, diagnosed 6 to 8 years prior to the study, was approached to participate. In total, 824 patients responded (78%), and 517 could be included in statistical analyses. It was shown that in inflammatory bowel disease HRQoL was indeed influenced by quality of care (particularly with regard to the parameters of "providing information," " costs," and "courtesy"), as well as by disease activity, psychological status, type of hospital, social support, stressful life events, and way of administration of the questionnaire. Patients with active disease had lower psychological status and HRQoL scores at the time of the survey than patients without active disease. However, quality of care scores did not differ between these groups. The care aspect "costs" was scored worse by CD compared with UC patients, probably caused by a potentially more expensive treatment. In conclusion, it is shown in a large exploratory study, for the first time, that in inflammatory bowel disease, quality of care has a significant role in determining health-related quality of life.

In the literature there are indications of associations between health-related quality of life (HRQoL) in inflammatory bowel disease and disease activity, psychological status, coping, stressful life events, and social support. The aim of this study was to examine whether a relation exists between quality of health care and HRQoL, taking possible confounding variables into account. For this purpose, one single questionnaire was compiled from existing validated questionnaires. A population-based inception cohort of 1056 patients with inflammatory bowel disease in eight countries, diagnosed 6 to 8 years prior to the study, was approached to participate. In total, 824 patients responded (78%), and 517 could be included in statistical analyses. It was shown that in inflammatory bowel disease HRQoL was indeed influenced by quality of care (particularly with regard to the parameters of "providing information," " costs," and "courtesy"), as well as by disease activity, psychological status, type of hospital, social support, stressful life events, and way of administration of the questionnaire. Patients with active disease had lower psychological status and HRQoL scores at the time of the survey than patients without active disease. However, quality of care scores did not differ between these groups. The care aspect "costs" was scored worse by CD compared with UC patients, probably caused by a potentially more expensive treatment. In conclusion, it is shown in a large exploratory study, for the first time, that in inflammatory bowel disease, quality of care has a significant role in determining health-related quality of life.

BACKGROUND: The role of mesalazine in preventing the clinical recurrence of Crohn's disease after surgery has been shown in a meta-analysis of all published studies. No clear relationship, however, has been shown between dosage and response. AIM: To evaluate whether 4.0 g/day of mesalazine may offer therapeutic advantages over 2.4 g/day in the prevention of both endoscopic and clinical post-operative recurrence of Crohn's disease. METHODS: The study was a double-blind, randomized, multi-centre, prospective, controlled clinical trial. Two hundred and six patients, submitted to first or second intestinal resection for Crohn's disease limited to the terminal ileum, with or without involvement of the caecum/ascending colon, were enrolled. Of these, 101 were randomly allocated to receive 4.0 g/day of mesalazine (Asacol, Giuliani SpA, Milan, Italy) and 105 to receive 2.4 g/day, starting 2 weeks after surgery. The primary outcome was endoscopic recurrence, at 12 months after surgery. Three different degrees of endoscopic recurrence were evaluated (endoscopic scores: > 0, > 1 and > 2). The secondary outcome was clinical recurrence, defined as a Crohn's disease activity index of more than 150 points or an increase in the Crohn's disease activity index of 100 points or more. For statistical analysis, chi-square, Wilcoxon and Cox regression model tests were used, when appropriate. RESULTS: Eighty-four patients in the 4.0 g/day group and 81 patients in the 2.4 g/day group were evaluable by endoscopy. Endoscopic recurrence of > 0 was significantly higher in the 2.4 g/day group than in the 4.0 g/day group (62% vs. 46%; P < 0.04). No difference was observed between the two groups with regard to the other two endoscopic outcomes (> 1 and > 2) or clinical recurrence. CONCLUSIONS: A 4.0 g/day regimen of mesalazine does not offer a clinically significant advantage over a 2.4 g/day regimen in the prevention of post-operative endoscopic and clinical recurrence of Crohn's disease at 1 ye

BACKGROUND: Although previous studies have shown increased mortality in patients with coeliac disease and their relatives, no data are available in relation to different patterns of clinical presentation. We assessed mortality in patients with coeliac disease and their first-degree relatives. METHODS: We enrolled, in a prospective cohort study, 1072 adult patients with coeliac disease consecutively diagnosed in 11 gastroenterology units between 1962 and 1994, and their 3384 first-degree relatives. We compared the number of deaths up to 1998 with expected deaths and expressed the comparison as standardised mortality ratio (SMR) and relative survival ratio. FINDINGS: 53 coeliac patients died compared with 25.9 expected deaths (SMR 2.0 [95% CI 1.5-2.7]). A significant excess of mortality was evident during the first 3 years after diagnosis of coeliac disease and in patients who presented with malabsorption symptoms (2.5 [1.8-3.4]), but not in those diagnosed because of minor symptoms (1.1 [0.5-2.2]) or because of antibody screening (1.2 [0.1-7.0]). SMR increased with increasing delay in diagnosis and for patients with poor compliance with gluten-free diet. Non-Hodgkin lymphoma was the main cause of death. No excess of deaths was recorded in relatives with coeliac disease. INTERPRETATION: Prompt and strict dietary treatment decreases mortality in coeliac patients. Prospective studies are needed to clarify the progression of mild or symptomless coeliac disease and its relation to intestinal lymphoma.

The distribution of HLA A, B, C, DR antigens was investigated in a British population with ulcerative colitis. Fifty six patients were typed for HLA, A, B, C and 46 additionally for DR. No association was found between the HLA phenotype and the presence or absence of ulcerative colitis. Serum from 52 patients was tested for the presence of the anticolon antibody. There was no relation between the presence of the antibody and the HLA phenotype. Finally, no correlation was found between the HLA phenotypes, the age of onset of the disease, the extent and the clinical course.

The distribution of HLA A, B, C, DR antigens was investigated in a British population with ulcerative colitis. Fifty six patients were typed for HLA, A, B, C and 46 additionally for DR. No association was found between the HLA phenotype and the presence or absence of ulcerative colitis. Serum from 52 patients was tested for the presence of the anticolon antibody. There was no relation between the presence of the antibody and the HLA phenotype. Finally, no correlation was found between the HLA phenotypes, the age of onset of the disease, the extent and the clinical course.