Sphingosine 1 phosphate S1P is a bioactive lipid mediator involved in the regulation of several cellular processes though the activation of a G protein-coupled receptor family known as the S1P ...receptors S1PRs. Advances in the understanding of the biological activities mediated by S1PRs have sparked great interest in the S1P/S1PRs axes as new therapeutic targets for the modulation of several cellular processes. In particular, the S1P/S1PR1 axis has been identified as key regulator for lymphocyte migration from lymph nodes. The blockade of this axis is emerging as a new therapeutic approach to control the aberrant leukocyte migration into the mucosa in inflammatory bowel disease IBD. This review briefly summarises the current evidence coming from clinical studies, and discusses the future prospects of S1P inhibitors for treatment of inflammatory bowel disease.
Colonoscopy CS is the standard for assessing disease activity in ulcerative colitis UC, although invasive and poorly tolerated. Bowel ultrasound BUS may be a valid alternative in UC patients; ...however, the comparative accuracy between BUS and CS is unknown.
Consecutive patients with UC were prospectively assessed by CS and BUS. Colonic wall thickening CWT >3 mm, colonic wall flow at power Doppler CWF, colonic wall pattern CWP, and presence of lymph nodes evaluated at BUS were compared with CS. The endoscopic activity was assessed according to the Mayo endoscopic sub-score 0-3. All BUS investigations were performed by two independent gastroenterologists and the kappa statistic for agreement was calculated. Ultrasonography-based criteria (Humanitas Ultrasound Criteria HUC) were developed.
A total of 53 UC patients 56% with left-sided colitis, 19% with pancolitis were prospectively enrolled. Of these, 22 patients had mucosal healing Mayo endoscopic sub-score 0-1 and 31 patients were in endoscopic activity. CWT, CWF, hypoechogenic CWP and the presence of lymph nodes significantly correlated with endoscopic activity p < 0.05. CWT p = 0.01 and CWF p = 0.09 were independent predictors for endoscopic activity. The HUC developed are: i the presence of a CWF and CWT > 3 mm; or ii the absence of a CWF and CWT > 4.43 mm. They showed high accuracy for the detection of disease activity sensitivity 0.71, specificity 1.00. The interobserver agreement for BUS was excellent kappa 0.86.
BUS is a non-invasive, easy-to-use tool to manage UC patients in clinical practice. HUC were very accurate in assessing disease activity in UC patients.
The risk of coronavirus disease-19 infection for healthcare professionals and patients in hospitals remains unclear.
We investigated whether precautions adopted in our inflammatory bowel disease ...(IBD) unit have minimized the risks of infection for all patients accessing our facilities in a 1-month period by assessing the rate of coronavirus disease-19 infection in the follow-up period.
Three hundred-twenty patients with IBD were included. None were infected from severe acute respiratory syndrome-coronavirus 2 in the follow-up period. None of the IBD team members were infected.
Neither pharmacological immunosuppression nor access to the hospital seem to be risk factors for infection in patients with IBD.
Alterations in signaling pathways that regulate resolution of inflammation (resolving pathways) contribute to pathogenesis of ulcerative colitis (UC). The resolution process is regulated by lipid ...mediators, such as those derived from the ω-3 docosahexaenoic acid (DHA), whose esterified form is transported by the major facilitator superfamily domain containing 2A (MFSD2A) through the endothelium of brain, retina, and placenta. We investigated if and how MFSD2A regulates lipid metabolism of gut endothelial cells to promote resolution of intestinal inflammation.
We performed lipidomic and functional analyses of MFSD2A in mucosal biopsies and primary human intestinal microvascular endothelial cells (HIMECs) isolated from surgical specimens from patients with active, resolving UC and healthy individuals without UC (controls). MFSD2A was knocked down in HIMECs with small hairpin RNAs or overexpressed from a lentiviral vector. Human circulating endothelial progenitor cells that overexpress MFSD2A were transferred to CD1 nude mice with dextran sodium sulfate–induced colitis, with or without oral administration of DHA.
Colonic biopsies from patients with UC had reduced levels of inflammation-resolving DHA-derived epoxy metabolites compared to healthy colon tissues or tissues with resolution of inflammation. Production of these metabolites by HIMECs required MFSD2A, which is required for DHA retention and metabolism in the gut vasculature. In mice with colitis, transplanted endothelial progenitor cells that overexpressed MFSD2A not only localized to the inflamed mucosa but also restored the ability of the endothelium to resolve intestinal inflammation, compared with mice with colitis that did not receive MFSD2A-overexpressing endothelial progenitors.
Levels of DHA-derived epoxides are lower in colon tissues from patients with UC than healthy and resolving mucosa. Production of these metabolites by gut endothelium requires MFSD2A; endothelial progenitor cells that overexpress MFSD2A reduce colitis in mice. This pathway might be induced to resolve intestinal inflammation in patients with colitis.
Over the past decades, the advent of anti-TNF agents has dramatically changed the treatment algorithms for IBD. However, primarily and more importantly, secondary loss of response to anti-TNF agents, ...is often observed. Thus, new treatment options have been actively explored and some have already been incorporated in the current clinical practice. Among the class of anti-cytokine agents, the anti-IL12/IL23 monoclonal antibodies (mAbs) have been first presented, in clinical practice, by the anti-p40 mAb ustekinumab in Crohn's disease (CD). More selective anti-IL23 agents (anti-p19) have shown efficacy and are being further developed, in contrast to agents inhibiting IL-17 downstream, which have failed in IBD clinical trials despite their clear efficacy in psoriasis.
The current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has required a complete change in the management of patients ...with inflammatory bowel disease (IBD) who need to undergo endoscopic procedures. Several preventive measures must be taken to avoid the spread of infection among health-care professionals and patients with IBD, including the use of personal protective equipment, greater attention to endoscopic room hygiene and rescheduling of non-urgent procedures. This Perspective aims to provide a guide based on the Italian and French experience to better face the difficulties encountered by endoscopists during this global health emergency. In particular, recommendations regarding the use of personal protective equipment to prevent COVID-19 transmission, both for patients and health-care professionals, are proposed and different scenarios in endoscopic IBD management are evaluated to suggest when endoscopy could be rescheduled and replaced by alternative biomarkers.
SARS-CoV-2 is a novel coronavirus that expanded worldwide, generating a pandemic of acute respiratory syndrome called "coronavirus disease 2019" (COVID-19), which resulted in a global health crisis. ...The spectrum of COVID-19 manifestations ranges from none or mild symptoms to severe respiratory failure associated with systemic manifestations, mostly gastrointestinal symptoms. Hypercoagulability is an important feature of COVID-19 disease, which can potentially influence patients' prognosis. Therefore, gastroenterologists should focus on subjects with concomitant hypercoagulable gastrointestinal disorders as they may display a higher risk of thrombotic complications during SARS-CoV-2 infection. The aim of this review is to summarize the available evidence regarding the interplay of the prothrombotic pathogenetic mechanisms of both COVID-19 and hypercoagulable digestive diseases and the possible clinical implications. We summarized the potential interplay of prothrombotic mechanisms of both COVID-19 and hypercoagulable digestive diseases in the graphical abstract.
The potential of endoscopic evaluation in the management of inflammatory bowel diseases (IBD) has undoubtedly grown over the last few years. When dealing with IBD patients, histological remission ...(HR) is now considered a desirable target along with symptomatic and endoscopic remission, due to its association with better long-term outcomes. Consequently, the ability of endoscopic techniques to reflect microscopic findings in vivo without having to collect biopsies has become of upmost importance. In this context, a more accurate evaluation of inflammatory disease activity and the detection of dysplasia represent two mainstay targets for IBD endoscopists. New diagnostic technologies have been developed, such as dye-less chromoendoscopy, endomicroscopy, and molecular imaging, but their real incorporation in daily practice is not yet well defined. Although dye-chromoendoscopy is still recommended as the gold standard approach in dysplasia surveillance, recent research questioned the superiority of this technique over new advanced dye-less modalities narrow band imaging (NBI), Fuji intelligent color enhancement (FICE), i-scan, blue light imaging (BLI) and linked color imaging (LCI). The endoscopic armamentarium might also be enriched by new video capsule endoscopy for monitoring disease activity, and high expectations are placed on the application of artificial intelligence (AI) systems to reduce operator-subjectivity and inter-observer variability. The goal of this review is to provide an updated insight on contemporary knowledge regarding new endoscopic techniques and devices, with special focus on their role in the assessment of disease activity and colorectal cancer surveillance.
Biosimilars present a considerable potential to reduce costs related to clinical management allowing health-care providers to reinvest this money, leading to a wider access to an effective biological ...treatment with monoclonal antibodies (mAb). Infliximab biosimilars have already been incorporated in daily clinical practice and are currently used in all indications for which the reference product (RP) was approved. Areas covered: In the next few years, also adalimumab biosimilars will become available for the treatment of inflammatory bowel disease (IBD). In fact, several of them (ABP501, BI 695501, GP2017, and SB5) have been approved by the European Medicines Agency (EMA) with the same indications of the reference product (Humira ®). Initial preclinical data proved a strong similarity between all biosimilars and the RP. Moreover, phase 3 studies in rheumatoid arthritis and psoriasis showed no differences in terms of efficacy, safety, and immunogenicity. Data on IBD patients are urgently needed. Expert opinion: Biosimilars of adalimumab showed equivalent clinical efficacy to the RP in other immunemediated diseases. However, defining the ideal patient's profile to receive or to be switched to a biosimilar, choosing one biosimilar vs. another, or cross-switching among biosimilars, will become the next challenge in IBD.
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