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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has a direct impact on the gastrointestinal system, as up to 50% of fecal samples from coronavirus disease 2019 (COVID-19) patients contain detectable viral RNA despite a negative rhino-pharyngeal swab. This finding, together with an intestinal expression of angiotensin conversion enzyme 2 protein, suggests a possible fecal-oral transmission for SARSCoV-2. Furthermore, gastrointestinal (GI) symptoms are common in COVID-19 patients including watery diarrhea, vomiting particularly in children nausea, and abdominal pain. Pathogenesis of SARS-CoV-2 infection presents significant similarities to those of some immune-mediated diseases, such as inflammatory bowel diseases or rheumatoid arthritis, leading to the hypothesis that targeted therapies used for the treatment of immune-mediated disease could be effective to treat (and possibly prevent) the main complications of COVID-19. In this review, we synthesize the present and future impact of SARS-CoV-2 infection on the gastrointestinal system and on gastroenterology practice, hypothesizing a potential role of the "gut-lung axis" and perhaps of the gut and lung microbiota into the interindividual differential susceptibility to COVID-19 19 disease. Finally, we speculate on the reorganization of outpatient gastroenterology services, which need to consider, among other factors, the major psychological impact of strict lockdown measures on the whole population.

Colorectal cancer (CRC) is one of the most prevalent and deadly forms of cancer in Western countries. Inflammation is a well-known driver of colonic carcinogenesis; however, its role in CRC extends beyond colitis-associated cancer. Over the last decades, numerous associations between intestinal dysbiosis and CRC have been identified, with more recent studies providing mechanistic evidence of a causative relationship. Nonetheless, much remains to be discovered regarding the precise implications of microbiome alterations in the pathogenesis of CRC. Research confirms the importance of a bidirectional crosstalk between the gut microbiome and the mucosal immune system in which inflammasomes, multiprotein complexes that can sense “danger signals,” serve as conduits by detecting microbial signals and activating innate immune responses, including the induction of microbicidal activities that can alter microbiome composition. Current evidence strongly supports an active role for this “inflammasome–microbiome axis” in the initiation and development of CRC. Furthermore, the gasdermin (GSDM) family of proteins, which are downstream effectors of the inflammasome that are primarily known for their role in pyroptosis, have been recently linked to CRC pathogenesis. These findings, however, do not come without controversy, as pyroptosis is reported to exert both anti- and protumorigenic functions. Furthermore, the multi-faceted interactions between GSDMs and the gut microbiome, as well as their importance in CRC, have only been superficially investigated. In this review, we summarize the existing literature supporting the importance of the inflammasome–microbiota axis, as well as the activation and function of GSDMs, to gain a better mechanistic understanding of CRC pathogenesis.

Background: During the COVID-19 pandemic, many inflammatory bowel disease (IBD) centres had to reorganise their work, and multidisciplinary teams, including IBD nurses, have had to try to deliver services to patients as safely as possible. Aims: This survey aimed to assess the thoughts, opinions and feelings of IBD patients on biologics regarding the efforts of IBD nurses to organise care during the COVID-19 pandemic. Methods: An evaluation survey based on an anonymous questionnaire was distributed to IBD nurses in five Italian IBD centres, in parallel. Findings: Of 306 participants, 55.6% had Crohn’s disease and 44.4% had ulcerative colitis. Most (79.1%) were aware of the specialist IBD nurse role, and 75.8% could distinguish it from generalist nurses. Of patients, 99.7% felt IBD nurses were competent to care for their condition and 91.2% felt that IBD nurses could provide valid scientific information. Meanwhile, 81.4% had a good or excellent relationship with their IBD nurse. Patients reported that most nurses wore personal protective equipment (94.4%), promoted self-care (91.8%), asked about presence of fever or cough (84.3%), asked about patient health status (83.7%) and covered pandemic safety and social distancing rules (69.3%), but fewer spoke about patient mood (44.4%) or relevant benefits, rules and exemptions (26.8%). Most participants (77.8%) faced pandemic-related issues for infusions. Nearly all (97.4%) knew immunosuppressed people were vulnerable to COVID-19, but only 42.8% spoke to their nurse about it. Some 61.8% of patients were concerned about COVID-19, but only 39.2% raised this with the IBD nurse. However, many more patients spoke to a nurse about concerns regarding biologics (41.8%) and worsening IBD symptoms (46.4%) in the pandemic than the actual number experiencing these issues (13.7% and 4.3%, respectively). Conclusion: The results show that IBD patients appreciate the role of the specialist nurse in their care.

Background: Data from trials of vedolizumab for inflammatory bowel disease and from real-world studies suggest an exposure-response relationship, such that vedolizumab trough levels may predict clinical and endoscopic outcomes. Objective: The purpose of this study was to evaluate in a prospective observational study the utility of an early vedolizumab trough level assay for predicting the first-year vedolizumab therapy outcome. Methods: This prospective observational study included consecutive inflammatory bowel disease patients. We measured vedolizumab trough levels and anti-vedolizumab antibodies at weeks 6 and 14. Clinical outcome was assessed at weeks 6, 14, 22 and 54. The primary endpoint was the correlation between early vedolizumab trough levels and vedolizumab persistence over the first year of treatment, defined as the maintenance of vedolizumab therapy due to sustained clinical benefit. Results: We included 101 patients initiating vedolizumab. A cut-off vedolizumab trough level of 16.55 µg/ml at week 14 predicted vedolizumab persistence within the first year of therapy, with 73.3% sensitivity and 59.4% specificity (p = 0.0009). Week 14 vedolizumab trough level was significantly higher in patients with clinical remission at weeks 14, 22 and 54; and in patients achieving mucosal healing within 54 weeks. Conclusion: High vedolizumab trough level at week 14 was associated with a higher probability of maintaining vedolizumab therapy over the first year due to sustained clinical benefit.

Background: Switching from IFX originator to CT-P13 is safe; however, little data on immunogenicity exists. Research design and methods: Consecutive IBD patients on IFX originator were switched to CT-P13 and followed-up for 12 months. Clinical activity, infliximab trough levels (ITLs), anti-drug antibodies (ATIs), and adverse events were recorded at predefined timepoints (baseline, second CT-P13 infusion, 6 and 12 months). The outcomes investigated were immunogenicity, pharmacokinetics, effectiveness and safety. Results: 119 patients were switched to CT-P13 after a median time with IFX of 5.8 years. No changes in mean ITLs were observed. ATIs were detected in 30 patients (25.2%): 14 before and 16 after switch. Mean persistent ATIs were significantly higher compared to mean transient ones (109.74 ng/mL ±84.70 vs 18.22 ng/mL ±11.37, p < 0.001), with significantly lower ITLs associated (mean 0.32 µg/mL ±0.6 vs 3.08 µg/mL ±3.22, p < 0.001). A significant decrease of patients in steroid-fee clinical remission was observed after the switch (p = 0.004), with subsequent improvement at 6 months (p = 0.005). Eighteen patients (15.1%) discontinued IFX, only 6 (5%) for loss of response. Conclusions: Switching from infliximab originator to CT-P13 seems safe and effective, without differences in immunogenicity. A temporary reduction of clinical benefit after switching could be potentially explained by a ‘nocebo-effect response’.

OBJECTIVE: The role of nurses has great educational-scientific potential in COVID-19 vaccination. The aim of this work is to clarify whether the educational role of IBD nurses in vaccination is perceived by IBD patients. MATERIALS AND METHODS: A cross-sectional study was carried out, through a questionnaire, to evaluate how many IBD patients received health education about vaccinations from the dedicated nurses (IBD nurses). RESULTS: There were four hundred questionnaires, 310 patients (77.5%) answered all questions. The nurse does not appear to help educate patients on influenza vaccination (66.1%) or pneumococcal vaccination (81.6%). Disclosed patients have many doubts about the new COVID-19 vaccination (74.4%) and many seek information (74.8%) and think that the nurse can provide the necessary information (70%). CONCLUSIONS: IBD nurses do not seem very active in the vaccination education role, and they do not meet patients’ expectations, which are conversely very high.

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Inflammatory bowel diseases (IBD) are chronic conditions that primarily affect the gas-trointestinal tract, with a complex pathogenesis; they are characterized by a significant heterogene-ity of clinical presentations and of inflammatory pathways that sustain intestinal damage. After the introduction of the first biological therapies, the pipeline of therapies for IBD has been constantly expanding, and a significant number of new molecules is expected in the next few years. Evidence from clinical trials and real-life experiences has taught us that up to 40% of patients do not respond to a specific drug. Unfortunately, to date, clinicians lack a valid tool that can predict each patient’s response to therapies and that could help them in choosing what drug to administer. Several candidate biomarkers have been investigated so far, with conflicting results: clinical, genetic, immuno-logical, pharmacokinetic and microbial markers have been tested, but no ideal marker has been identified so far. Based on recent evidence, multiparametric models seemingly hold the greatest potential for predicting response to therapy. In this narrative review, we aim to summarize the current knowledge on predictors and early markers of response to biological therapies in IBD.

Background: Combining immunosuppressors has been proposed as a strategy to enhance treatment efficacy in Inflammatory Bowel Disease (IBD). Aim: To summarize current evidence on combinations of targeted therapies with traditional immunosuppressors or with other targeted therapies. Methods: A literature search on PubMed and Medline databases was performed to identify relevant articles. Results: Current evidence supports that the combination of infliximab and thiopurines is more effective than monotherapy with both agents in inducing remission in Crohn's Disease and Ulcerative colitis. Data on other combinations of other biologics and traditional immunosuppressors is lacking or show conflicting results. Vedolizumab seems a potentially effective maintenance regimen after calcineurin inhibitors-based rescue therapy in acute severe ulcerative colitis, as an alternative to thiopurines. Dual Targeted Therapy, which is the combination of 2 targeted therapies, might be a reasonable choice in patients with concomitant IBD and extraintestinal manifestations, or in patients with medical-refractory IBD who lack valid alternatives. Combinations with thiopurines are associated with an increased risk of infections and lymphoma. Data on other combinations is scarcer, but no specific safety issue has emerged so far. Conclusions: Combination therapies seem to be effective in selected patients, with an overall acceptable safety profile.

Inflammatory bowel disease (IBD) is a chronic condition that requires continuous medical treatment. To date, the medical management of patients with moderately-to-severely active IBD who develop dependence or resistance to corticosteroids is based on immunomodulator drugs. Such therapies are licenced after passing through three phases of randomized controlled trials (RCTs), and are subsequently adopted in clinical practice. However, the real-life population of IBD patients who require these therapies can significantly differ from those included in RCTs. As a matter of fact, there is a number of exclusion criteria – nearly ubiquitous in all RCTs – that prevent the enrolment of specific patients: Chronic refractory pouchitis or isolated proctitis in ulcerative colitis, short-bowel syndrome and stomas in Crohn’s disease, ileorectal anastomosis in both ulcerative colitis and Crohn’s disease, and elderly age are some representative examples. In this frontier article, we aim to give an overview of current literature on this topic, in order to address the main knowledge gaps that need to be filled in the upcoming years.

Inflammatory bowel disease (IBD) management has changed dramatically over the past 20 years, after the introduction of targeted biological therapies. However, the impact of these new drugs in changing the natural history of disease is still under debate. Recent evidence seems to suggest that the extent of their efficacy might be, at least partially, dependent on the timing of their introduction and on the subsequent management strategy. In this complex landscape, the potential role for a more dynamic approach with treatments based on sequencing and combining targeted therapies has been explored only minimally so far. In this review, we aim to explore the potential biological rationale behind the use of sequential and combination therapies in IBD, to summarise the current knowledge on this topic and to propose a management algorithm that combines these notions.

Personalized Medicine (PM) has shifted the traditional top-down approach to medicine based on the identification of single etiological factors to explain diseases, which was not suitable for explaining complex conditions. The concept of PM assumes several interpretations in the literature, with particular regards to Genetic and Genomic Medicine. Despite the fact that some disease-modifying genes affect disease expression and progression, many complex conditions cannot be understood through only this lens, especially when other lifestyle factors can play a crucial role (such as the environment, emotions, nutrition, etc.). Personalizing clinical phenotyping becomes a challenge when different pathophysiological mechanisms underlie the same manifestation. Brain disorders, cardiovascular and gastroentero-logical diseases can be paradigmatic examples. Experiences on the field of Fondazione Policlinico Gemelli in Rome (a research hospital recognized by the Italian Ministry of Health as national leader in “Personalized Medicine” and “Innovative Biomedical Technologies”) could help understanding which techniques and tools are the most performing to develop potential clinical phenotypes person-alization. The connection between practical experiences and scientific literature highlights how this potential can be reached towards Systems Medicine using Artificial Intelligence tools.

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Background: Combining immunosuppressors has been proposed as a strategy to enhance treatment efficacy in Inflammatory Bowel Disease (IBD). Aim: To summarize current evidence on combinations of targeted therapies with traditional immunosuppressors or with other targeted therapies. Methods: A literature search on PubMed and Medline databases was performed to identify relevant articles. Results: Current evidence supports that the combination of infliximab and thiopurines is more effective than monotherapy with both agents in inducing remission in Crohn's Disease and Ulcerative colitis. Data on other combinations of other biologics and traditional immunosuppressors is lacking or show conflicting results. Vedolizumab seems a potentially effective maintenance regimen after calcineurin inhibitors-based rescue therapy in acute severe ulcerative colitis, as an alternative to thiopurines. Dual Targeted Therapy, which is the combination of 2 targeted therapies, might be a reasonable choice in patients with concomitant IBD and extraintestinal manifestations, or in patients with medical-refractory IBD who lack valid alternatives. Combinations with thiopurines are associated with an increased risk of infections and lymphoma. Data on other combinations is scarcer, but no specific safety issue has emerged so far. Conclusions: Combination therapies seem to be effective in selected patients, with an overall acceptable safety profile.

Crohnʹs disease (CD) is a chronic inflammatory bowel disease with a progressive course, potentially affecting the entire gastrointestinal tract from mouth to anus. Several studies have shown an increased risk of both intestinal and extra‐intestinal cancer in patients with CD, due to long‐standing transmural inflammation and damage accumulation. The similarity of symptoms among CD, its related complications and the de novo onset of gastrointestinal cancer raises difficulties in the differential diagnosis. In addition, once a cancer diagnosis in CD patients is made, selecting the appropriate treatment can be particularly challenging. Indeed, both surgical and oncological treatments are not always the same as that of the general population, due to the inflammatory context of the gastrointestinal tract and the potential exacerbation of gastrointestinal symptoms of patients with CD; moreover, the overlap of the neoplastic disease could lead to adjustments in the pharmacological treatment of the underlying CD, especially with regard to immunosuppressive drugs. For these reasons, a case‐by‐case analysis in a multidisciplinary approach is often appropriate for the best diagnostic and therapeutic evaluation of patients with CD after gastrointestinal cancer onset.