The oft-overlooked cardiovascular complications of inflammatory bowel disease.

INTRODUCTION: Inflammatory bowel disease (IBD) may be associated with several extraintestinal comorbidities, including cardiovascular disease (CVD). Chronic inflammation is recognized as an important factor in atherogenesis, thrombosis, and myocarditis. AREAS COVERED: IBD patients may be at increased risk for developing early atherosclerosis, cardiovascular events, peripheral artery disease, venous thromboembolism, myocarditis, and arrhythmias. Anti-tumor necrosis factor agents and thiopurines have been shown to have a protective effect against acute arterial events, but more research is needed. However, an increased risk of venous thromboembolism and major cardiovascular events has been described with the use of Janus kinase inhibitors. EXPERT OPINION: CVD risk is slightly increased in patients with IBD, especially during flares. Thromboprophylaxis is strongly recommended in hospitalized patients with active disease as the benefit of anticoagulation outweighs the risk of bleeding. The pathogenetic relationship between CVD and IBD and the impact of IBD drugs on CVD outcomes are not fully elucidated. CVD risk doesn't have the strength to drive a specific IBD treatment. However, proper CVD risk profiling should always be done and the best strategy to manage CVD risk in IBD patients is to combine appropriate thromboprophylaxis with early and durable remission of the underlying IBD.

Acute mesenteric ischemia and small bowel imaging findings in COVID-19: A comprehensive review of the literature.

BACKGROUND: Coronavirus disease 2019 (COVID-19), an infectious condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread worldwide since its first description in Wuhan in December 2019. Even though respiratory manifestations are the most prevalent and responsible for disease morbidity and mortality, extrapulmonary involvement has progressively gained relevance. In particular, gastrointestinal (GI) signs and symptoms, reported in up to two-thirds of patients with COVID-19, might represent the first and, in some cases, the only disease presentation. Their presence has been associated in some studies with an increased risk of a severe disease course. Proposed pathogenic mechanisms explaining GI tract involvement are either direct viral access to intestinal cells via angiotensin-converting enzyme 2 or indirect damage of the intestinal wall through mesenteric ischemia induced by the hypercoagulable state associated with COVID-19 infection. Although not typical of SARS-CoV-2 infection, several small bowel manifestations have been described in infected patients who underwent any form of abdominal imaging. The radiological findings were mainly reported in patients with abdominal symptoms, among which abdominal pain was the most common. AIM: To discuss small bowel radiological manifestations of SARS-CoV-2 infection in abdominal imaging studies. METHODS: Bibliographical searches were performed in PubMed, using the following keywords: "COVID-19" AND "imaging" AND "gastrointestinal" OR "abdominal" OR "small bowel". RESULTS: Of 62 patients with described radiologic small bowel alterations, mesenteric ischemia was diagnosed in 31 cases (50%), small bowel wall thickening in 10 cases (16%), pneumatosis in nine cases (15%), intussusception in eight cases (13%), pneumoperitoneum in two cases (3%) and paralytic ileus in two cases (3%). We also reported mesenteric adipose tissue hypertrophy and lymph nodes enlargement in a young woman. CONCLUSION: So far it is difficult to establish whether these manifestations are the direct consequence of SARS-CoV-2 infection or collateral findings in infected patients, but their recognition would be pivotal to set a closer follow-up and to reduce missed diagnoses.

Virtual Chromoendoscopy With FICE for the Classification of Polypoid and Nonpolypoid Raised Lesions in Ulcerative Colitis.

GOALS: The aim of this study was to analyze the performance of Fuji Intelligent Color Enhancement (FICE) using the classification of Kudo in the differentiation of neoplastic and non-neoplastic raised lesions in ulcerative colitis (UC). BACKGROUND: The Kudo classification of mucosal pit patterns is an aid for the differential diagnosis of colorectal polyps in the general population, but no systematic studies are available for all forms of raised lesions in UC. STUDY: All raised, polypoid and nonpolypoid, lesions found during consecutive surveillance colonoscopies with FICE for long-standing UC were included. In the primary prospective analysis, the Kudo classification was used to predict the histology by FICE. In a post hoc analysis, further endoscopic markers were also explored. RESULTS: Two hundred and five lesions (mean size, 8 mm; range, 2 to 30 mm) from 59 patients (mean age, 56 y; range, 21 to 79 y) were analyzed. Twenty-three neoplastic (11%), 18 hyperplastic (9%), and 164 inflammatory (80%) lesions were found. Thirty-one lesions (15%), none of which were neoplastic, were unclassifiable according to Kudo. After logistic regression, a strong negative association resulted between endoscopic activity and neoplasia, whereas the presence of a fibrin cap was significantly associated with endoscopic activity. Using FICE, the sensitivity, specificity, and positive and negative likelihood ratios of the Kudo classification were 91%, 76%, 3.8, and 0.12, respectively. The corresponding values by adding the fibrin cap as a marker of inflammation were 91%, 93%, 13, and 0.10, respectively. CONCLUSIONS: FICE can help to predict the histology of raised lesions in UC. A new classification of pit patterns, based on inflammatory markers, should be developed in the setting of UC to improve the diagnostic performance.

Mongersen, an oral SMAD7 antisense oligonucleotide, and Crohn's disease.

BACKGROUND: Crohn's disease-related inflammation is characterized by reduced activity of the immunosuppressive cytokine transforming growth factor ß1 (TGF-ß1) due to high levels of SMAD7, an inhibitor of TGF-ß1 signaling. Preclinical studies and a phase 1 study have shown that an oral SMAD7 antisense oligonucleotide, mongersen, targets ileal and colonic SMAD7. METHODS: In a double-blind, placebo-controlled, phase 2 trial, we evaluated the efficacy of mongersen for the treatment of persons with active Crohn's disease. Patients were randomly assigned to receive 10, 40, or 160 mg of mongersen or placebo per day for 2 weeks. The primary outcomes were clinical remission at day 15, defined as a Crohn's Disease Activity Index (CDAI) score of less than 150, with maintenance of remission for at least 2 weeks, and the safety of mongersen treatment. A secondary outcome was clinical response (defined as a reduction of 100 points or more in the CDAI score) at day 28. RESULTS: The proportions of patients who reached the primary end point were 55% and 65% for the 40-mg and 160-mg mongersen groups, respectively, as compared with 10% for the placebo group (P<0.001). There was no significant difference in the percentage of participants reaching clinical remission between the 10-mg group (12%) and the placebo group. The rate of clinical response was significantly greater among patients receiving 10 mg (37%), 40 mg (58%), or 160 mg (72%) of mongersen than among those receiving placebo (17%) (P=0.04, P<0.001, and P<0.001, respectively). Most adverse events were related to complications and symptoms of Crohn's disease. CONCLUSIONS: We found that study participants with Crohn's disease who received mongersen had significantly higher rates of remission and clinical response than those who received placebo. (Funded by Giuliani; EudraCT number, 2011-002640-27.).

ABO histo-blood group might modulate predisposition to Crohn's disease and affect disease behavior.

BACKGROUND AND AIMS: ABO encodes a glycosyltranferase which determines the major human histo-blood group. The FUT2 fucosyltransferase allows expression of ABO antigens on the gastrointestinal mucosa and in bodily secretions (secretor phenotype). A nonsense allele in FUT2 represents a susceptibility variant for Crohn's disease, and both the secretor and ABO blood group status affect the composition of the gut microbiota. Thus, we evaluated if variants in ABO might represent good candidates as Crohn's disease susceptibility loci. METHODS: We recruited two case-control cohorts, from Italy (n=1301) and Belgium (n=2331). Subjects were genotyped for one SNP in FUT2 and two variants in ABO. RESULTS: No effect on Crohn's disease risk was detected for ABO variants, whereas an association was observed between the FUT2 polymorphism and Crohn's disease susceptibility in the Belgian sample, but not in the Italian cohort. The effect of histo-blood groups was evaluated using group O as the reference. Most non-O groups had odds ratios (ORs) higher than 1 in both cohorts, and combined analysis of the two samples indicated a predisposing effect for the A and B groups (OR=1.17, 95% CI: 1.02-1.32 and OR=1.33, 95% CI: 1.09-1.58, respectively). In Crohn's disease patients, the non-O blood group and the non-secretor status were associated with higher risk of developing a stricturing or penetrating disease. CONCLUSIONS: ABO histo-blood group might confer susceptibility to Crohn's disease and modulate disease severity.

Crohn's disease loci are common targets of protozoa-driven selection.

Previous studies indicated that a few risk variants for autoimmune diseases are subject to pathogen-driven selection. Nonetheless, the proportion of risk loci that has been targeted by pathogens and the type of infectious agent(s) that exerted the strongest pressure remain to be evaluated. We assessed whether different pathogens exerted a pressure on known Crohn's disease (CD) risk variants and demonstrate that these single-nucleotide polymorphisms (SNPs) are preferential targets of protozoa-driven selection (P = 0.008). In particular, 19% of SNPs associated with CD have been subject to protozoa-driven selective pressure. Analysis of P values from genome-wide association studies (GWASs) and meta-analyses indicated that protozoan-selected SNPs display significantly stronger association with CD compared with nonselected variants. This same behavior was not observed for GWASs of other autoimmune diseases. Thus, we integrated selection signatures and meta-analysis results to prioritize five genic SNPs for replication in an Italian cohort. Three SNPs were significantly associated with CD risk, and combination with meta-analysis results yielded P values < 4 × 10(-6). The bona fide risk alleles are located in ARHGEF2, an interactor of NOD2, NSF, a gene involved in autophagy, and HEBP1, encoding a possible mediator of inflammation. Pathway analysis indicated that ARHGEF2 and NSF participate in a molecular network, which also contains VAMP3 (previously associated to CD) and is centered around miR-31 (known to be disregulated in CD). Thus, we show that protozoa-driven selective pressure had a major role in shaping predisposition to CD. We next used this information for the identification of three bona fide novel susceptibility loci.