Personalize, participate, predict, and prevent: 4Ps in inflammatory bowel disease

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC), is a complex, immune-mediated, disorder which leads to several gastrointestinal and systemic manifestations determining a poor quality of life, disability, and other negative health outcomes. Our knowledge of this condition has greatly improved over the last few decades, and a comprehensive management should take into account both biological (i.e., disease-related, patient-related) and non-biological (i.e., socioeconomic, cultural, environmental, behavioral) factors which contribute to the disease phenotype. From this point of view, the so called 4P medicine framework, including personalization, prediction, prevention, and participation could be useful for tailoring ad hoc interventions in IBD patients. In this review, we discuss the cutting-edge issues regarding personalization in special settings (i.e., pregnancy, oncology, infectious diseases), patient participation (i.e., how to communicate, disability, tackling stigma and resilience, quality of care), disease prediction (i.e., faecal markers, response to treatments), and prevention (i.e., dysplasia through endoscopy, infections through vaccinations, and post-surgical recurrence). Finally, we provide an outlook discussing the unmet needs for implementing this conceptual framework in clinical practice

Use of biosimilars in inflammatory bowel diseases: A survey among the clinicians members of the Italian Group for the Study of Inflammatory Bowel Disease (IGIBD)

The first infliximab biosimilar for the treatment of inflammatory bowel disease (IBD) was introduced in 2013, and today eight anti-TNF alpha biosimilars (three for infliximab and five for adalimumab) have been approved and licensed by the European Medicines Agency. Biosimilars present great potential in terms of cost saving and possible consequential reinvestment in the health care system. The increasing knowledge about the process of biosimilar development and use in IBD and the publication of many prospective clinical studies and real-life clinical experiences have progressively changed the point of view of IBD physicians. In the present position paper, the Italian Group for the Study of Inflammatory Bowel Disease present and discuss their updated statements and positions on this topic, with emphasis on the concepts of biosimilarity and extrapolation across indications, safety and immunogenicity, interchangeability and switching, automatic substitution, and, finally, patient education about biosimilars

Nutrition in Patients with Inflammatory Bowel Diseases: A Narrative Review

Inflammatory bowel diseases (IBD) affect the gastrointestinal tract: they include Crohn’s disease (CD) and ulcerative colitis (UC). Each has a different phenotypic spectrum, characterized by gastrointestinal and extra-intestinal manifestations. People living with IBD are very interested in diet, but little is known about the impact of diet on these patients; no guidelines are available yet. In this review, we analyze the dietary patterns of patients with IBD and the approach to the choices of foods both in adults and pediatric patients. Very often, IBD patients report an intentional avoidance of gluten to manage the disease; furthermore, a proportion of IBD patients believe that dairy products worsen their symptoms and that avoidance may help the disease. They have a low compliance with the Mediterranean Diet, which is considered to have potential benefits but is little used in practice. In conclusion, the review underscores the pivotal role of nutritional counselling in IBD patients, and the importance of future clinical studies to evaluate the beneficial effects of dietary recommendations in the management of IBD

Microbiota dysbiosis influences immune system and muscle pathophysiology of dystrophin‐deficient mice

Abstract Duchenne muscular dystrophy (DMD) is a progressive severe muscle‐wasting disease caused by mutations in DMD, encoding dystrophin, that leads to loss of muscle function with cardiac/respiratory failure and premature death. Since dystrophic muscles are sensed by infiltrating inflammatory cells and gut microbial communities can cause immune dysregulation and metabolic syndrome, we sought to investigate whether intestinal bacteria support the muscle immune response in mdx dystrophic murine model. We highlighted a strong correlation between DMD disease features and the relative abundance of Prevotella. Furthermore, the absence of gut microbes through the generation of mdx germ‐free animal model, as well as modulation of the microbial community structure by antibiotic treatment, influenced muscle immunity and fibrosis. Intestinal colonization of mdx mice with eubiotic microbiota was sufficient to reduce inflammation and improve muscle pathology and function. This work identifies a potential role for the gut microbiota in the pathogenesis of DMD

ATP-gated ionotropic P2X7 receptor controls follicular T helper cell numbers in Peyer's patches to promote host-microbiota mutualism.

Microbial colonization of the gut induces the development of gut-associated lymphoid tissue (GALT). The molecular mechanisms that regulate GALT function and result in gut-commensal homeostasis are poorly defined. T follicular helper (Tfh) cells in Peyer's patches (PPs) promote high-affinity IgA responses. Here we found that the ATP-gated ionotropic P2X7 receptor controls Tfh cell numbers in PPs. Lack of P2X7 in Tfh cells enhanced germinal center reactions and high-affinity IgA secretion and binding to commensals. The ensuing depletion of mucosal bacteria resulted in reduced systemic translocation of microbial components, lowering B1 cell stimulation and serum IgM concentrations. Mice lacking P2X7 had increased susceptibility to polymicrobial sepsis, which was rescued by Tfh cell depletion or administration of purified IgM. Thus, regulation of Tfh cells by P2X7 activity is important for mucosal colonization, which in turn results in IgM serum concentrations necessary to protect the host from bacteremia

COVID-19 Vaccination Willingness and Hesitancy in Patients With Inflammatory Bowel Diseases: Analysis of Determinants in a National Survey of the Italian IBD Patients' Association

Vaccine hesitancy and willingness in patiente and parents of patients with inflammatory bowel diseas

Translation and initial validation of the Medication Adherence Report Scale (MARS) in Italian patients with Crohn's Disease

The MARS-5 (Medication Adherence Report Scale) was developed in English. The aim of this project was to analyse the MARS-5I (\ua9 Prof Rob Horne) psychometric properties and to identify whether its Italian translation is suitable for assessing medication adherence in Crohn Disease (CD) Italian patients. The MARS was translated and linguistically validated in Italian. The MARS-5I was used for evaluating medication adherence in the SOLE study, conducted in Italy on 552 subjects with CD. In order to un-bias the questionnaire results from the effects of treatment change and/or effectiveness, the analyses were performed on the 277 patients whose disease activity remained stable, selected among the 371 patients who maintained the same treatment between two consecutive visits. Internal consistency was high (Cronbach's alpha of 0.86). Pearson's correlation coefficient was 0.50 (p < 0.001) and 0.86 (p < 0.001- outliers removed), indicating satisfactory test-retest. MARS 5I scores were not correlated with Treatment Satisfaction Questionnaire for Medication but a small and statistically significant correlation was shown with physician-evaluated medication adherence, indicating convergent validity. MARS-5I, the Italian translation of the English MARS, showed satisfactory internal consistency and test-retest, and a low but statistically significant convergent validity. We confirmed the utility of this tool in patients with CD

SARS-CoV-2 infection in patients with inflammatory bowel disease: comparison between the first and second pandemic waves

Background: In Italy, the incidence of SARS-CoV-2 infection peaked in April and November 2020, defining two pandemic waves of coronavirus disease 2019 (COVID-19). This study compared the characteristics and outcomes of patients with inflammatory bowel disease (IBD) and SARS-CoV-2 infections between pandemic waves. Methods: Observational longitudinal study of IBD patients with SARS-CoV-2 infection. Patients with established diagnoses of IBD and of SARS-CoV-2 infection were consecutively enrolled in two periods: (i) first wave, from 1 March 2020 to 31 May 2020; and (ii) second wave, from 15 September to 15 December 2020. Results: We enrolled 937 IBD patients (219 in the first wave, 718 in the second wave). Patients of the first wave were older (mean ± SD: 46.3 ± 16.2 vs. 44.1 ± 15.4 years, p = 0.06), more likely to have ulcerative colitis (58.0% vs. 44.4%, p < 0.001) and comorbidities (48.9% vs. 38.9%; p < 0.01), and more frequently residing in Northern Italy (73.1% vs. 46.0%, p < 0.001) than patients of the second wave. There were no significant differences between pandemic waves in sex (male: 54.3% vs. 53.3%, p = 0.82) or frequency of active IBD (44.3% vs. 39.0%, p = 0.18). The rates of negative outcomes were significantly higher in the first than second wave: pneumonia (27.8% vs. 11.7%, p < 0.001), hospital admission (27.4% vs. 9.7%, p < 0.001), ventilatory support (11.9% vs. 5.4%, p < 0.003) and death (5.5% vs. 1.8%, p < 0.007). Conclusion: Between the first and second SARS-CoV-2 pandemic waves, demographic, clinical and geographical features of IBD patients were different as were the symptoms and outcomes of infection. These differences are likely due to the different epidemiological situations and diagnostic possibilities between the two waves