assessment of crohn s disease activity magnetic resonance enterography in comparison with clinical and endoscopic evaluations

Crohn's disease (CD) is a chronic inflammatory transmural disease of the gastrointestinal tract. The small bowel is the most frequently involved site. Assessment of the bowel is essential in guiding therapeutic decisions, medical or surgical therapy. Personalized medicine is a new concept that has the potential to improve therapeutic efficacy, reduce the risk of drug adverse events, and decrease costs if the therapy is the most suitable treatment for selected patients. Many techniques have been verified and standardised for small bowel CD. Among radiological techniques, CT enterography (CTE) and MRI-enterography (MRE) are the most widely accepted techniques, although MRI is generally preferable as it avoids radiation. In this review, we will present the current role and new innovative technological perspectives of MR enterography in comparison with clinical and endoscopic evaluations for the assessment of CD activity in adult patients. In particular, many studies have been performed to validate MRE signs such as biomarkers of active Crohn's disease (such as mural thickening, mural T2 hyperintense signal, target sign, comb sign, ulceration and extramural mesenteric signs) and to select the most appropriate index for identifying active disease or severe inflammation (such as MaRIA score, Clermont index, and others). We conclude that MRE is a minimally invasive tool for the evaluation of disease activity and shows a very good correlation with the presence and severity of endoscopic lesions, so to allow a personalized medicine in patients with CD

Interleukin-1β blockade reduces intestinal inflammation in a murine model of Tumor Necrosis Factor-independent ulcerative colitis

Background & aimsInflammatory bowel diseases (IBDs) are multifactorial diseases commonly treated with either immunomodulatory drugs or anti-tumor necrosis factor (TNF). Currently, failure to respond to anti-TNF therapy (assessed not prior to 8-12 weeks after starting treatment) occurs in 20-40% of patients enrolled in clinical trials and 10-20% in clinical practice. Murine models of IBD provide important tools to better understand disease mechanism(s). In this context and among the numerous models available, Winnie-TNF-KO mice were recently reported to display characteristics of ulcerative colitis (UC) that are independent of TNF, and with increased IL-1β production.MethodsHerein, the efficacy of recombinant (r) IL-1 receptor antagonist (IL-1Ra, Anakinra) administration was evaluated in Winnie-TNF-KO mice, utilized as an UC model of primary anti-TNF non-responders.ResultsWe analyzed gut mucosal biopsies and circulating cytokine profiles of a cohort of 30 UC patients; approximately 75% of primary non-responders were characterized by abundant IL-1β in both the serum and local intestinal tissues. In Winnie-TNF-KO mice, administration of Anakinra efficiently reduced the histological score of the distal colon, which represents the most common site of inflammation in Winnie mice. Furthermore, among lamina propria and mesenteric lymph node-derived T cells, IFNγ-expressing CD8+ T cells were significantly reduced following Anakinra administration.ConclusionsOur study provides new insight and alternative approaches to treat UC patients, and point to anti-IL-1 strategies (i.e., Anakinra) that may be a more effective therapeutic option for primary non-responders to anti-TNF therapy

International consensus conference on stool banking for faecal microbiota transplantation in clinical practice

Although faecal microbiota transplantation (FMT) has a well-established role in the treatment of recurrent Clostridioides difficile infection (CDI), its widespread dissemination is limited by several obstacles, including lack of dedicated centres, difficulties with donor recruitment and complexities related to regulation and safety monitoring. Given the considerable burden of CDI on global healthcare systems, FMT should be widely available to most centres. Stool banks may guarantee reliable, timely and equitable access to FMT for patients and a traceable workflow that ensures safety and quality of procedures. In this consensus project, FMT experts from Europe, North America and Australia gathered and released statements on the following issues related to the stool banking: general principles, objectives and organisation of the stool bank; selection and screening of donors; collection, preparation and storage of faeces; services and clients; registries, monitoring of outcomes and ethical issues; and the evolving role of FMT in clinical practice, Consensus on each statement was achieved through a Delphi process and then in a plenary face-to-face meeting. For each key issue, the best available evidence was assessed, with the aim of providing guidance for the development of stool banks in order to promote accessibility to FMT in clinical practice.Peer reviewe

Nutrition and IBD: Malnutrition and/or Sarcopenia? A Practical Guide

Malnutrition is a major complication of inflammatory bowel disease (IBD). This mini review is focusing on main determinants of malnutrition in IBD, the most important components of malnutrition, including lean mass loss and sarcopenia, as an emerging problem. Each one of these components needs to be well considered in a correct nutritional evaluation of an IBD patient in order to build a correct multidisciplinary approach. The review is then focusing on possible instrumental and clinical armamentarium for the nutritional evaluation

Harmful Effects and Potential Benefits of Anti-Tumor Necrosis Factor (TNF)-α on the Liver

Anti-tumor necrosis factor (TNF)-α agents represent an effective treatment for chronic inflammatory diseases. However, some concerns about their potentially undesirable effects on liver function have been reported. On the other hand, evidence of their therapeutic effects on certain liver diseases is accumulating. Many data showed the safety of anti-TNF-α in patients with chronic hepatitis B and C and in liver transplanted patients even if a strict follow-up and prophylaxis are recommended in well-defined subgroups. On the other side, anti-TNF-α-induced liver injury is not a rare event. However, it is often reversible after anti-TNF-α withdrawal. Anti-TNF-α agents have been tested in advanced stages of severe alcoholic hepatitis and non-alcoholic fatty liver disease. Limited data on the efficacy of anti-TNF-α in patients with autoimmune hepatitis and primary biliary cholangitis are also available. In this review, we explored the hepatic safety concerns in patients receiving anti-TNF-α agents with and without pre-existent hepatic diseases. In addition, the available evidence on their potential benefits in the treatment of specific hepatic diseases is discussed

Opposing functions of classic and novel IL-1 family members in gut health and disease

In addition to their well-established role(s) in the pathogenesis of gastrointestinal (GI)-related inflammatory disorders, including inflammatory bowel disease (IBD) and inflammation-associated colorectal cancer (CRC), emerging evidence confirms the critical involvement of the interleukin-1 (IL-1) cytokine family and their ligands in the maintenance of normal gut homeostasis. In fact, the paradigm that IBD occurs in two distinct phases is substantiated by the observation that classic IL-1 family members, such as IL-1, the IL-1 receptor antagonist (IL-1Ra), and IL-18, possess dichotomous functions depending on the phase of disease, as well as on their role in initiating vs. sustaining chronic gut inflammation. Another recently characterized IL-1 family member, IL-33, also possesses dual functions in the gut. IL-33 is upregulated in IBD and potently induces Th2 immune responses, while also amplifying Th1-mediated inflammation. Neutralization studies in acute colitis models, however, have yielded controversial results and recent reports suggest a protective role of IL-33 in epithelial regeneration and mucosal wound healing. Finally, although little is currently known regarding the potential contribution of IL-36 family members in GI inflammation/homeostasis, another IL-1 family member, IL-37, is emerging as a potent anti-inflammatory cytokine with the ability to downregulate colitis. This new body of information has important translational implications for both the prevention and treatment of patients suffering from IBD and inflammation-associated CRC

Fighting the Hype for Predictors of Efficacy in Inflammatory Bowel Disease

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Immune system and gut microbiota senescence in elderly IBD patients

In inflammatory bowel disease (IBD), the loss of immune tolerance against gut microbiota causes chronic inflammation and the progressive accumulation of organ damage in genetically susceptible individuals. In the elderly, IBD is often characterized by a different disease behaviour when compared with paediatric and young adult disease. Besides disease behaviour, another aspect of the multifaceted impact of age on elderly IBD course is increased susceptibility to infections. In this context, age-of-onset-dependent IBD behaviour and clinical course are two major contributors to immune system senescence and change of gut microbiota in older subjects. Here, we review the available literature linking immunosenescence and age-dependent changes in the gut microbiota composition to IBD pathogenesis speculating on their possible implications in disease expression in this age class

Focus on Anti-Tumour Necrosis Factor (TNF)-α-Related Autoimmune Diseases

Anti-tumour necrosis factor (TNF)-α agents have been increasingly used to treat patients affected by inflammatory bowel disease and dermatological and rheumatologic inflammatory disorders. However, the widening use of biologics is related to a new class of adverse events called paradoxical reactions. Its pathogenesis remains unclear, but it is suggested that cytokine remodulation in predisposed individuals can lead to the inflammatory process. Here, we dissect the clinical aspects and overall outcomes of autoimmune diseases caused by anti-TNF-α therapies

Interleukin 1β Blockade Reduces Intestinal Inflammation in a Murine Model of Tumor Necrosis Factor-Independent Ulcerative Colitis

BACKGROUND & AIMS: Inflammatory bowel diseases are multifactorial diseases commonly treated with either immunomodulatory drugs or anti-tumor necrosis factor (TNF). Currently, failure to respond to anti-TNF therapy (assessed no earlier than 8-12 weeks after starting treatment) occurs in 20%-40% of patients enrolled in clinical trials and in 10%-20% in clinical practice. Murine models of inflammatory bowel disease provide important tools to better understand disease mechanism(s). In this context and among the numerous models available, Winnie-TNF-knockout (KO) mice recently were reported to show characteristics of ulcerative colitis (UC) that are independent of TNF, and with increased interleukin (IL)1 beta production.METHODS: Herein, the efficacy of recombinant IL1-receptor antagonist (anakinra) administration was evaluated in Winnie-TNF-KO mice, used as a UC model of primary anti-TNF nonresponders.RESULTS: We analyzed gut mucosal biopsy specimens and circulating cytokine profiles of a cohort of 30 UC patients; approximately 75% of primary nonresponders were characterized by abundant IL1 beta in both the serum and local intestinal tissues. In Winnie-TNF-KO mice, administration of anakinra efficiently reduced the histologic score of the distal colon, which represents the most common site of inflammation in Winnie mice. Furthermore, among lamina propria and mesenteric lymph node-derived T cells, interferon gamma-expressing CD8(+) T cells were reduced significantly after anakinra administration.CONCLUSIONS: Our study provides new insight and alternative approaches to treat UC patients, and points to anti-IL1 strategies (ie, anakinra) that may be a more effective therapeutic option for primary nonresponders to anti-TNF therapy