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Item does not contain fulltext BACKGROUND: Inflammatory bowel disease (IBD) care and education might differ around Europe. Therefore, we conducted this European Variation In IBD PracticE suRvey (VIPER) to investigate potential differences between countries. METHODS: This trainee-initiated survey, run through SurveyMonkey®, consisted of 47 questions inquiring basic demographics, IBD training, and clinical care. Results were compared according to gross domestic product (GDP) per capita, for which countries were divided into 2 groups (low/high income, according to the World Bank). RESULTS: The online survey was completed by 1,285 participants from 40 European countries, with a majority of specialists (65.3%) working in academic institutions (50.4%). Significant differences in IBD-specific training (55.9% vs. 38.4%), as well as availability of IBD units (58.4% vs. 39.7%) and multidisciplinary meetings (73.2% vs. 40.1%), were observed between respondees from high and low GDP countries (p < 0.0001). In high GDP countries, IBD nurses are more common (85.9% vs. 36.0%), also mirrored by more nurse-led IBD clinics (40.6% vs. 13.7%; p < 0.0001). IBD dieticians (33.4% vs. 16.5%) and psychologists (16.8% vs. 7.5%) are mainly present in high GDP countries (p < 0.0001). In the current COVID era, telemedicine is available in 73.2% versus 54.1% of the high/low GDP countries, respectively (p < 0.0001). Treat-to-target approaches are implemented everywhere (85.0%), though access to biologicals and small molecules differs significantly. CONCLUSION: Much variability in IBD practice exists across Europe, with marked differences between high and low GDP countries. Further work is required to help address some of these inequalities, aiming to improve and standardize IBD care and training across Europe.

iNKT cells account for a relevant fraction of effector T-cells in the intestine and are considered an attractive platform for cancer immunotherapy. Although iNKT cells are cytotoxic lymphocytes, their functional role in colorectal cancer (CRC) is still controversial, limiting their therapeutic use. Thus, we examined the immune cell composition and iNKT cell phenotype of CRC lesions in patients (n = 118) and different murine models. High-dimensional single-cell flow-cytometry, metagenomics, and RNA sequencing experiments revealed that iNKT cells are enriched in tumor lesions. The tumor-associated pathobiont Fusobacterium nucleatum induces IL-17 and Granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in iNKT cells without affecting their cytotoxic capability but promoting iNKT-mediated recruitment of neutrophils with polymorphonuclear myeloid-derived suppressor cells-like phenotype and functions. The lack of iNKT cells reduced the tumor burden and recruitment of immune suppressive neutrophils. iNKT cells in-vivo activation with α-galactosylceramide restored their anti-tumor function, suggesting that iNKT cells can be modulated to overcome CRC-associated immune evasion. Tumor co-infiltration by iNKT cells and neutrophils correlates with negative clinical outcomes, highlighting the importance of iNKT cells in the pathophysiology of CRC. Our results reveal a functional plasticity of iNKT cells in CRC, suggesting a pivotal role of iNKT cells in shaping the tumor microenvironment, with relevant implications for treatment.

ObjectivesUlcerative colitis (UC) is a chronic inflammatory disorder of unknown aetiology. Gut virome dysbiosis is fundamental in UC progression, although its role in the early phases of the disease is far from fully understood. Therefore, we sought to investigate the role of a virome-associated protein encoded by theOrthohepadnavirusgenus, the hepatitis B virus X protein (HBx), in UC aetiopathogenesis.DesignHBx positivity of UC patient-derived blood and gut mucosa was assessed by RT-PCR and Sanger sequencing and correlated with clinical characteristics by multivariate analysis. Transcriptomics was performed on HBx-overexpressing endoscopic biopsies from healthy donors.C57BL/6 mice underwent intramucosal injections of liposome-conjugated HBx-encoding plasmids or the control, with or without antibiotic treatment. Multidimensional flow cytometry analysis was performed on colonic samples from HBx-treated and control animals. Transepithelial electrical resistance measurement, proliferation assay, chromatin immunoprecipitation assay with sequencing and RNA-sequencing were performed onin vitromodels of the gut barrier. HBx-silencing experiments were performedin vitroandin vivo.ResultsHBx was detected in about 45% of patients with UC and found to induce colonic inflammation in mice, while its silencing reverted the colitis phenotypein vivo. HBx acted as a transcriptional regulator in epithelial cells, provoking barrier leakage and altering both innate and adaptive mucosal immunityex vivoandin vivo.ConclusionThis study described HBx as a contributor to the UC pathogenesis and provides a new perspective on the virome as a target for tailored treatments.

iNKT cells account for a relevant fraction of effector T-cells in the intestine. Although iNKT cells are cytotoxic lymphocytes, their role in colorectal cancer (CRC) remains controversial. From the analysis of colonic LPMCs of human and murine CRC specimens we report that tumor-infiltrating iNKT cells are characterized by an IL17/GM-CSF pro-tumorigenic phenotype, while maintaining cytotoxic properties in the adjacent non-tumoral tissue. Exposure of iNKT cells to the tumor-associated pathobiontFusobacterium nucleatumblunted their cytotoxic capability and enhanced iNKT cell-mediated neutrophils chemotaxis, which upregulated PMN-MDSC gene signatures and functions. Importantly,in vivostimulation of iNKT cells with αGalCer restored their anti-tumorigenic functions. Survival analyses demonstrated that human CRC co-infiltration by iNKT cells and tumor-associated neutrophils correlates with negative outcomes.Our results reveal a functional plasticity of human intestinal iNKT cells with pro- and anti-tumorigenic activities in CRC, suggesting an iNKT pivotal role in shaping the cancer developmental trajectory.

The coronavirus disease 2019 (COVID-19) pandemic has not finished yet, and the most promising option towards its ending is widespread vaccination. Because patients with inflammatory bowel diseases (IBDs), namely Crohn’s disease (CD) and ulcerative colitis (UC), often require immune-modifying treatment, which might increase the risk of opportunistic infection,1 their vaccination history for several infectious diseases is routinely checked, and when inadequate, vaccination is performed at diagnosis or ideally before immune suppressive treatment is started.1 However, IBD patients were not found to be at an increased risk of developing COVID-19 or of experiencing a more severe disease course.2

Background Gastrointestinal infections represent a risk factor for functional gastrointestinal and somatoform extraintestinal disorders. We investigated the prevalence and relative risk (RR) of gastrointestinal and somatoform symptoms 5 months after SARS‐CoV‐2 infection compared with a control cohort. Methods One hundred and sixty‐four SARS‐CoV‐2 infected patients and 183 controls responded to an online questionnaire about symptoms and signs during the acute phase of the infection and after 4.8 ± 0.3 months. Presence and severity of gastrointestinal symptoms, somatization, anxiety, and depression were recorded with standardized questionnaires. Stool form and presence of irritable bowel syndrome (IBS) were also recorded. Any association between exposure to infection and symptoms was evaluated by calculating crude and adjusted RR values and score differences with 95% confidence intervals (CI). Key Results Fever, dyspnea, loss of smell/taste/weight, diarrhea, myalgia, arthralgia, and asthenia were reported by more than 40% of patients during the acute phase. Compared with controls, adjusted RRs for loose stools, chronic fatigue, and somatization were increased after infection: 1.88 (95% CI 0.99–3.54), 2.24 (95% CI 1.48–3.37), and 3.62 (95% CI 1.01–6.23), respectively. Gastrointestinal sequelae were greater in patients with diarrhea during the acute phase. Conclusions & Inferences Mild gastroenterological symptoms persist 5 months after SARS‐CoV‐2 infection, in particular in patients reporting diarrhea in the acute phase. Infected patients are at increased risk of chronic fatigue and somatoform disorders, thus supporting the hypothesis that both functional gastrointestinal and somatoform disorders may have a common biological origin., Mild gastrointestinal symptoms persist 5 months after SARS‐CoV‐2 infection together with an increased risk of chronic fatigue and somatoform symptoms. These results support the hypothesis that both functional gastrointestinal and somatoform disorders may have a common biological origin.

To the Editors, We thank Drs. R. Mungmunpuntipantip and V. Wiwanitkit1 for their comment on our recently published article, “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”.

Background and AimsA similar course of COVID-19 in patients with inflammatory bowel diseases [IBD] and in the general population has been reported. However, disease prevalence in IBD patients is presently unknown. In this prospective observational study, we aimed at determining SARS-CoV2 infection prevalence in IBD patients treated with biologic therapy.MethodsFrom IBD patients under biologic therapy and recruited from three different locations in Italy and Germany, 354 sera were evaluated for antibody presence by RBD ELISA. Control groups were: i] age-matched healthy subjects tested in the same time period in Milan, Italy; ii] healthy subjects collected in the pre-COVID era; iii] IBD patients under biologic therapy collected in the pre-COVID era.ResultsEight out of 354 patients tested positive for the anti-RBD-SARS-CoV2 IgG antibody [prevalence 2.3%]. The percentage of IgG-positive patients among those recruited from Milan was significantly higher than among those recruited from other locations [prevalence 5.4% vs 0.4%, p ConclusionsSeroprevalence of SARS-CoV2 in IBD patients treated with biologic therapy reflects values measured in the local general population. Specific symptoms and contact history with SARS-CoV2-infected individuals strongly increase the likelihood of SARS-CoV2 seropositivity.

Background Vaccine hesitancy, the delay in acceptance or refusal of vaccination despite its availability, represents a threat to the diffusion and lethality of infectious diseases. COVID-19 vaccination has been recommended by national and international organizations in patients with Inflammatory Bowel Diseases (IBD). The aim of the study was to evaluate COVID-19 vaccine willingness and hesitancy in a population of Italian patients with IBD, and their determinants. Methods In February 2021 an online questionnaire focused on COVID-19 vaccine was proposed to a representative sample of Italian IBD patients. Socio-demographic characteristics, IBD features, lifestyle, perception of COVID-19, general attitude towards vaccinations and to COVID-19 vaccines were investigated. Patients were divided into willing, hesitant and refusive towards COVID-19 vaccine. The hesitation reasons were investigated. The associations between baseline characteristics and willingness (determinants) were evaluated by calculating crude and adjusted Odds Ratio (AdjOR) with 95% confidence intervals (CI). Results The baseline characteristics are shown below. 1252 surveys were collected. 1005 (80.3%), 222 (18.1%) and 33 (2.63 %) patients were defined as willing, hesitant and refusive, respectively. Concerns for vaccine adverse effects constituted the main reason for refusal (73.4%) (Figure). 49.1% of hesitant patients reported that presence of IBD exerted an influence on their answer. Among the patients willing to be vaccinated whenever possible, 78.2% (786) thought that their IBD represented a valid motivation to access vaccination with priority. Willingness to COVID-19 vaccine was significantly associated with adherence to previous vaccinations (AdjOR 17.6, 95% CI 11.4–27.2), male gender (1.68 95% CI 1.16–2.43), graduation degree (1.48, 95% CI 1.03–2.13), perceived higher risk of COVID-19 due to IBD (1.47, 95% CI 1.05–2.08), alcohol intake (1.69, 95% CI 1.16–2.45). Conversely, the hesitancy was significantly associated with use of complementary and alternative medicines (0.58, 95% CI 0.36–0.92). Notably, 54.5% of patients were under the impression to have a higher risk of COVID-19 and 31.8% a more severe course due to their IBD. Conclusion Most IBD patients would accept COVID-19 vaccines, though one out of five is hesitant to date, principally due to fear of adverse events. The knowledge of determinants and reasons for COVID-19 vaccination acceptance could be a key element in developing targeted communication strategies to address vaccine hesitancy.

Background and Aim During the recent COVID-19 pandemic, telemedicine has enabled many IBD patients worldwide to get access to remote assistance. Some positive reports on the use of telemedicine among patients and healthcare providers have been published1-4, but a patient’s trust perspective is not available yet. The aim of our study was to verify IBD patients’ trust in telemedicine. This study was approved by our local Ethics Committee. Material and Methods At our Gastroenterology Unit in Milan (Italy), 123 video-consultations were delivered to IBD patients with mild or moderate disease, in place of follow-up visits scheduled but not provided during the general lockdown (March-April 2020). Video-calling solutions from Google (Hangouts or Meet) or Microsoft Teams were used according to the patient’s preference. The patients’ trust in telemedicine was assessed through an adapted version of the PAtient Trust Assessment Tool (PATAT) questionnaire.5 The primary endpoint was expressed as a >75% percentage of patients giving a score of at least 4 out of 5 in a Likert Scale for three selected key statements: “I can trust video-consultation”, “I can trust that possible problems with the telemedicine service will be solved properly” and “I feel at ease when working with this website”. The questionnaire was formulated through the EUSurvey platform, widely used for clinical research questionnaires in Europe. Results One-hundred-fifteen (93.4%) video-consultations were performed out of the 123 scheduled. Among the 115 consultations, 100 questionnaires were completed (86.9%). The primary endpoint of trust in the telemedicine service was achieved in 95%, 90% and 84% of patients for the three selected key statements about the trust in the telemedicine service, its capability to solve clinical problems and its ease to use. While clinical outcomes were beyond our intentions, we reported no drugs withdrawal in this cohort nor major events. Conclusion Our results showed that during the COVID-19 pandemic most of our IBD patients accepted to receive a video-consultation in spite of the traditional in-person visit and trusted the video-consultation. References: 1. Bezzio C. et al. Gut 2020;69:1213–1217 2. George L.A., Raymond K. Current Gastroenterology Reports (2020) 22: 12 3. Lees C. W. et al. Gastroenterology 2020; 2020 May 28 4. Allocca M et al. Clin Gastroenterol Hepatol 2020;18:1882–1883 5. Velsen, L. V. et al, H. Int. J. Med. Inform 2017;97:52–58.