Background: Inflammatory bowel diseases (IBDs) are chronic progressive conditions, and their management has evolved over time, not only in the number of available medications but also in therapeutic strategies, resulting in a paradigm shift from treat-on-flare to treat-to-target, with the ultimate goal of modifying disease course. Several studies have shown a reduction in the risk of surgery associated with the concomitant increase in anti-tumor necrosis factor α (TNFα) drug prescription, thus inferring a positive impact of anti-TNFα therapy on IBD natural history. However, establishing a causal relationship is complex, as multiple factors influence disease progression. Methods: To investigate this relationship, a narrative review applying the Bradford-Hill criteria to the existing literature has been conducted. Results: The potential causal link between the introduction and increased use of biologic drugs, particularly anti-TNFα agents, and the reduction in surgical risk in patients affected by IBD are critically reviewed. Conclusions: Establishing a direct causal link between increased anti-TNFα prescriptions and long-term outcomes remains a difficult issue. Multiple factors like greater awareness, early diagnosis, multidisciplinary approaches, introduction of guidelines, and ongoing education also contribute to improved prognosis.

SummaryBackgroundFew data are available addressing the impact of post‐operative management of Crohn's disease (CD) on long‐term clinical course.AimTo assess the evolution of post‐operative management strategies over the last 40 years and their impact on the re‐operation rate of CD.MethodsWe included 657 patients with CD who had undergone their first radical ileo‐caecal resection between 1980 and 2020. Three cohorts were defined according to year of surgery: cohort 1 (1980–1998; n = 198), cohort 2 (1999–2009; n = 218) and cohort 3 (2010–2020; n = 241). We estimated exposure to immunomodulators and anti‐TNFα agents after surgery and rates of re‐operation using Kaplan–Meier survival analyses. We used Cox proportional hazards regression to assess the association of clinical variables with time to re‐operation.ResultsImmunosuppressants, (IMMs) and anti‐TNFα exposure within 5 years after surgery increased significantly from cohort 1 to cohort 2 and cohort 3 (IMMs: 1.6%, 38.2% and 28.0%, respectively, p < 0.001; anti‐TNFα: 0.0%, 20.7% and 52.0%, respectively, p < 0.001). There was no significant difference across cohorts regarding the cumulative probability of re‐operation within 5 and 10 years. Multivariate analysis identified IMMs/anti‐TNFα exposure before the first surgery (HR 9.15; 95% CI 2.77–30.21) and post‐operatively (HR: 0.24; 95% CI 0.07–0.74) as variables associated with the risk of re‐operation. However, these associations had a time‐varying effect and become non‐significant after 5 and 2 years after surgery, respectively.ConclusionDespite increased post‐operative use of IMMs and anti‐TNFα agents in the last two decades, the impact of these strategies on the risk of long‐term re‐operation rate has been modest.

Objectives: Elderly hospitalized patients with inflammatory bowel disease (IBD) flare and concurrent Clostridioides difficile infection (CDI) are considered at high risk of IBD-related complications. We aimed to evaluate the short-,intermediate-, and long-term post-discharge complications among these patients. Methods: A retrospective multicenter cohort study assessing outcomes of elderly individuals (>= 60 years) hospitalized for an IBD flare who were tested for CDI (either positive or negative) and discharged. The primary outcome was the 3-month post-discharge IBD-related complication rates defined as steroid dependency, re-admissions (emergency department or hospitalization), IBD-related surgery, or mortality. We assessed post-discharge IBD-related complications within 6 month and mortality at 12 month among secondary outcomes. Risk factors for complication were assessed by multivariable logistic regression. Results: In a cohort of 654 patients hospitalized for IBD {age 68.9 (interquartile range [IQR]): 63.9-75.2 years, 60.9% ulcerative colitis (UC)}, 23.4% were CDI-positive. Post-discharge complication rates at 3 and 6 months, and 12 months mortality, did not differ significantly between CDI-positive and CDI-negative patients (32% vs 33.1%, p = 0.8; 40.5% vs 42.5%, p = 0.66; and 4.6% vs 8%, p = 0.153, respectively). The Charlson comorbidity index was the only significant risk factor for complications within 3 months (aOR 1.1), whereas mesalamine (5-aminosalicylic acid [5-ASA]) use was protective (aOR 0.6). An UC diagnosis was the sole risk factor for complication at 6 months (aOR 1.5). Clostridioides difficile infection did not significantly impact outcomes or interact with IBD type. Conclusions: In elderly IBD patients hospitalized for IBD flare and subsequently discharged, a concurrent CDI infection was not associated with post-discharge IBD-related complications or mortality up to 1 year.

Spondyloarthritis (SpA) is the most frequent extraintestinal manifestation in patients with inflammatory bowel diseases (IBD). When IBD and spondyloarthritis coexist, musculoskeletal and intestinal disease features should be considered when planning a therapeutic strategy. Treatment options for IBD and SpA have expanded enormously over the last few years, but randomized controlled trials with specific endpoints focused on SpA are not available in the IBD setting. To address this important clinical topic, the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) and the Italian Society of Rheumatology (SIR) jointly planned to draw updated therapeutic recommendations for IBD-associated SpA using a pseudo-Delphi method. This document presents the official recommendations of IG-IBD and SIR on the management of IBD-associated SpA in the form of 34 statements and 4 therapeutic algorithms. It is intended to be a reference guide for gastroenterologists and rheumatologists dealing with IBD-associated SpA.

We appreciate the interest of Dai, Huang and Jiang [ [1] Dai C Huang YH Jiang M. Use of biologics for the management of Crohn's disease. Dig Liver Dis. 2023; 55: 989 Abstract Full Text Full Text PDF Google Scholar ] in the clinical guidelines of the Italian Group for the Study of Inflammatory Bowel Disease (IG-IBD) on the use of biologics for the management of Crohn's disease (CD) [ [2] Macaluso FS Papi C Orlando A et al. Use of biologics for the management of Crohn's disease: IG-IBD clinical guidelines based on the GRADE methodology. Dig Liver Dis. 2023; 55: 442-453 Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar ]. The key for answering the issues raised by the colleagues lies in the technical review that accompanies the guidelines and provides a detailed analysis of the evidence upon which the IG-IBD clinical recommendations are based [ [3] Bonovas S, Piovani D, Pansieri C, et al. Use of biologics for the management of Crohn's disease: IG-IBD technical review based on the GRADE methodology. Dig Liver Dis. 2023:S1590-8658(23)00484-X Google Scholar ]. Use of biologics for the management of Crohn's diseaseDigestive and Liver DiseaseVol. 55Issue 7PreviewWe read with interest the article by Macaluso et al. developing new guidelines focused on the use of biologics for managing the intestinal manifestations of Crohn's disease (CD) and based on the GRADE methodology [1]. The author points out that there is very low-quality evidence for ustekinumab (UST) to treat adults with moderate-to-severe CD refractory to conventional therapy who are naive to biologics and at least one biologic. Because these statements are different from previous guidelines and important to current practice, several questions deserve attention. Full-Text PDF

Background/Aims: Endoscopic stenting for stricturing Crohn's disease (CD) is an emerging treatment that achieves more persistent dilatation of the stricture over time than endoscopic balloon dilatation (EBD). We aimed to explore the efficacy and safety of stenting for the treatment of CD strictures.Methods: A systematic electronic literature search was performed (PROSPERO; no. CRD42022308033). The primary outcomes were technical success, efficacy, complication rate, and the need for further interventions due to reobstruction. The outcomes of partially covered self-expanding metal stents (PCSEMS) with scheduled retrieval after seven days were also analyzed.Results: Eleven eligible studies were included in the review. Overall, 173 patients with CD were included in this study. Mean percentage of technical success was 95% (range, 80%–100%), short-term efficacy was 100% in all studies, and long-term efficacy was 56% (range, 25%–90%). In patients with a scheduled PCSEMS retrieval, the long-term efficacy was 76% (range, 59%–90%), the mean complication rate was 35% (range, 15%–57%), and the major complication rate was 11% (range, 0%–29%).Conclusions: Endoscopic stenting with scheduled PCSEMS retrieval may be considered a feasible second-line treatment for short CD strictures to postpone surgery. However, larger head-to-head prospective studies are needed to understand the role of stenting as an alternative or additional treatment to EBD in CD.

A cure for Crohn's disease (CD), a chronic inflammatory disease of the gastrointestinal tract of unknown etiology, is not available, so patients require lifelong management to keep inflammation under control. The therapeutic armamentarium has expanded with approval of several biological drugs, including infliximab, adalimumab, vedolizumab and ustekinumab – monoclonal antibodies that target different inflammatory pathways – and darvadstrocel, a suspension of expanded human allogeneic, adipose-derived, mesenchymal stromal cells for the treatment of refractory complex perianal fistula. Notwithstanding existing practice guidelines on medical therapy for CD, the Italian Group for the Study of Inflammatory Bowel Disease felt the need to issue new guidelines focused on the use of biologics for managing the intestinal manifestations of CD and based on the GRADE methodology. This document presents recommendations regarding six clinical settings, from the induction to the maintenance of clinical remission, and from optimization and de-escalation of treatments to dealing with perianal CD and post-operative recurrence. The 19 evidence-based statements are supported by information on the quality of the evidence, agreement rate among panel members, and panel comments mainly based on evidence from real world studies.

The authors report a case of synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in a patient with Crohn’s disease (CD). SAPHO syndrome is a rare disease characterised by the association, even if not simultaneous, of joint and skin manifestations. A young patient with CD was admitted to the authors’ hospital for the onset of bloody diarrhoea, persistent chest pain, headache, and fever while on maintenance therapy with vedolizumab. At visit, sternocostoclavicular and temporomandibular joints were tender and painful. Magnetic resonance was performed, and showed bone oedema of involved joints, while ileocolonoscopy revealed ulcers in the transverse colon. At laboratory, tests marked phlogosis and Campylobacter jejuni infection was observed. A challenge in differential diagnosis arose: atypical drug-induced extraintestinal manifestations, reactive arthritis, or extraintestinal manifestation directly associated with intestinal flare? In relation to the patient’s age, the involved joints, and magnetic resonance findings, SAPHO syndrome was diagnosed. Systemic steroids were used with a rapid clinical improvement; vedolizumab was withdrawn and ustekinumab was started with sustained clinical response.

Inflammatory bowel diseases (IBD) are chronic, progressive and relapsing inflammatory disorders of unknown etiology that may cause disability over time. Data from epidemiologic studies indicate that diet may play a role in the risk of developing and the course of IBD. It is known that the group of beneficial bacteria was reduced in the IBD and that the Mediterranean diet (MD)—which is defined as eating habits characterized by high consumption of plant foods, mainly cereals, vegetables, fruit as well as olive oil, and small portions of dairy products, sweets, sugar and meat products—affects gut microbiota, enriching beneficial bacteria, which support gut barrier function and reduce inflammation. Although several studies support different favorable effects of MD on IBD, adherence to MD by IBD patients is generally low, including patients from the Mediterranean Basin. Patients avoid many products which are elements of MD because there cause gastrointestinal symptoms. Patients should be encouraged to have a healthy and well-balanced diet according to individual tolerance of products. A good option seems to be good modified MD, changing hard-to-digest products to easy digest.

We have recently used Tofacitinib (TOFA) in a patient with severe ulcerative colitis (UC) refractory to intensive intravenous steroid treatment (IIVT) and with concomitant SARS-CoV-2 infection. Data addressing characteristics and outcomes of TOFA-treated UC patients with COVID-19 are limited and, to our knowledge, no cases of intentional TOFA therapy for steroid refractory UC in COVID-19 patients have been reported.

Colorectal cancer (CRC) risk is increased in Inflammatory Bowel Disease (IBD) and surveillance needs to be tailored according to individual risk. The open issues include the role of the characteristics of IBD and CRC in determining the long-term outcome. These issues were assessed in our multicenter study, including a cohort of 56 IBD patients with incident CRC. The clinical and histopathological features of IBD patients and of CRC were recorded. Incident CRC in IBD occurred at a young age (≤40 years) in 25% of patients (median age 55.5 (22–76)). Mucinous signet-ring carcinoma was detected in 6 out of the 56 (10.7%) patients, including 4 with Ulcerative Colitis (UC) and 2 with Crohn’s disease (CD). CRC was more frequently diagnosed by colonoscopy in UC (85.4% vs. 50%; p = 0.01) and by imaging in Crohn’s Disease CD (5.8% vs. 31.8%; p = 0.02). At onset, CRC-related symptoms occurred in 29 (51.9%) IBD patients. The time interval from the diagnosis of IBD to CRC was shorter in UC and CD patients with >40 years (p = 0.002; p = 0.01). CRC-related death occurred in 10 (29.4%) UC and in 6 (27.2%) CD patients (p = 0.89), with a short time interval from CRC to death (UC vs. CD: 6.5 (1–68) vs. 14.5 (8–40); p = 0.85; IBD: 12 months (1–68)). CRC occurring at a young age, a short time interval from the diagnosis of IBD to CRC-related death in the elderly, CRC-symptoms often mimicking IBD relapse and the observed high mortality rate may support the need of closer surveillance intervals in subgroups of patients.

Background Gastroenteropancreatic neuroendocrine neoplasms [GEP-NENs] have rarely been reported in association with inflammatory bowel diseases [IBDs]. Methods An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collects cases of GEP-NENs diagnosed in patients with IBD. Results GEP-NEN was diagnosed in 100 IBD patients; 61% female, 55% Crohn’s disease, median age 48 years (interquartile range [IQR] 38-59]). The most common location was the appendix [39%] followed by the colon [22%]. Comprehensive IBD-related data were available for 50 individuals with a median follow-up of 30 months [IQR 11-70] following NEN diagnosis. Median duration of IBD at NEN diagnosis was 84 months [IQR 10-151], and in 18% of cases NEN and IBD were diagnosed concomitantly. At diagnosis, 20/50 were stage-I [T1N0M0], and 28/50 were graded G1 [ki67 ≤2%]. Incidental diagnosis of NEN and concomitantly IBD diagnosis were associated with an earlier NEN stage [p = 0.01 and p = 0.02, respectively]. Exposure to immunomodulatory or biologic therapy was not associated with advanced NEN stage or grade. Primary GEP-NEN were more frequently found in the segment affected by IBD [62% vs 38%]. At the last follow-up data, 47/50 patients were alive, and only two deaths were related to NEN. Conclusions In the largest case series to date, prognosis of patients with GEP-NEN and IBD seems favourable. Incidental NEN diagnosis correlates with an earlier NEN stage, and IBD-related therapies are probably independent of NEN stage and grade. The association of GEP-NEN location and the segment affected by IBD may suggest a possible role of inflammation in NEN tumorigenesis

Background: The effectiveness of ustekinumab in patients with refractory Crohn’s disease (CD) has been investigated in several real-world studies. However, very few data concerning the real-life experience in Italy have been reported. Therefore, this study assessed the effectiveness of ustekinumab in a large cohort of Italian patients with refractory CD. Methods: All patients who had started on ustekinumab after failure of or intolerance to antitumour necrosis factor-α (TNF-α) treatment at five tertiary centres between November 2018 and February 2020 were retrospectively enrolled. The coprimary outcome was corticosteroid-free clinical remission, defined as a Harvey–Bradshaw Index (HBI) score of ⩽4, at weeks 26 and 52. The secondary outcomes were changes in the HBI and C-reactive protein (CRP) values at weeks 8, 26, and 52 from baseline and the normalization of CRP in patients with initially abnormal values. Results: Totally, 140 patients who had previously received at least one anti-TNF-α agent were enrolled; 40.0% received two anti-TNF-α agents and 20.0% received vedolizumab. At baseline, 108 patients (77.1%) had HBI scores of >4; of these, 56.5% and 58.3% achieved corticosteroid-free clinical remission at weeks 26 and 52, respectively. Significant decreases in HBI and CRP values were observed at weeks 8, 26, and 52 in the entire study cohort (all p < 0.0001). The CRP values were normalized in 34.9%, 37.8%, and 49.3% of the patients by weeks 8, 26, and 52, respectively. The baseline HBI score of ⩾8 was a negative predictor of corticosteroid-free clinical remission at week 52 (odds ratio: 0.21, 95% confidence interval: 0.08–0.56, p = 0.002). The probability of remaining on ustekinumab after 52 weeks was 92.1%. Eleven (7.9%) patients discontinued ustekinumab (three for adverse events). Conclusion: Our study findings confirm the effectiveness and safety of ustekinumab in patients with CD after failure of or intolerance to anti-TNF-α therapy.

The management of moderate to severe ulcerative colitis has undergone significant changes over the past 15 years due to the regulatory approval of several new drugs. In particular, following the approval of the first biological, i.e. infliximab, a number of further biological drugs, such as adalimumab, golimumab, vedolizumab and ustekinumab, and small molecules, such as tofacitinib, have been approved, thus enriching the therapeutic armamentarium for ulcerative colitis. Choice of therapy must take into consideration not only the need to induce and maintain disease remission according to the patient's profile, but also age, co-morbidities, and prior treatments. To guide these decisions, the Italian Group for the Study of Inflammatory Bowel Disease has developed clinical guidelines that supersede its earlier document from 2011. These new guidelines were developed following the GRADE methodology for rating the quality of the evidence and for determining the strength of the recommendations. This article presents the methodology and results, in the form of 20 statements with commentary on the use of the five biologics and tofacitinib for managing the intestinal manifestations of active ulcerative colitis and for maintaining remission. A separate technical review reports the analyses of the evidence upon which the present recommendations are based.

The drug pipeline for the treatment of inflammatory bowel disease (IBD) has dramatically expanded over the last two decades, and it is expected to further grow in the upcoming years with the introduction of new agents with different mechanisms of action. However, such an increase of therapeutic options needs to be paralleled with an appropriate development of research to help physicians in the decision-making process when choosing which drug to prescribe. On the population level, comparative effectiveness research (CER) is intended to explore and identify relevant differences-in terms of both efficacy and safety outcomes-amongst different therapeutic regimens and/or strategies, in order to find the correct placement for each treatment in the therapeutic algorithm. CER revolves around three cornerstones: network meta-analyses, head-to-head trials and real-world studies, each of which has specific pros and cons, and can therefore offer answers to different questions. In this review, we aim to provide an overview on the methodological features specific to each of these research approaches, as well as to illustrate the main findings coming from CER on IBD target therapies (i.e., biologics and small molecules) and to discuss their appropriate interpretation.

BACKGROUND & AIMS: Colonoscopy (CS) is the gold standard to assess postoperative recurrence (POR) in Crohn's disease (CD). However, CS is invasive and may be poorly tolerated by patients. The aim of this study was to prospectively assess the diagnostic accuracy of a noninvasive approach in detecting POR, using the endoscopic Rutgeerts' score (RS) as the reference standard. METHODS: Consecutive patients with CD who underwent ileo-cecal resection were prospectively enrolled in 3 referral Italian centers. Patients underwent CS and bowel ultrasound within 1 year of surgery. Uni-and multivariable analyses were used to assess the correlation between nonin-vasive parameters and endoscopic recurrence, defined by a RS >= 2. RESULTS: Ninety-one patients were enrolled. Sixty patients (66%) experienced endoscopic POR. The multivariable analysis identified bowel wall thickness (BWT) per 1-mm increase (odds ratio [OR], 2.43; 95% confidence interval [CI], 1.21-4.89; P = .012), the presence of mesenteric lymph nodes (OR, 15.63; 95% CI, 1.48-164.54; P = .022), and fecal calprotectin (FC) values >= 50 mcg/g (OR, 8.58; 95% CI, 2.45-29.99; P < .001) as independent predictors for endoscopic recurrence. The presence of lymph nodes or the combination of BWT >= 3 mm and FC values >= 50 mcg/g correctly classified 56% and 75% of patients, with less than 5% of patients falsely classified as having endoscopic recurrence. Conversely, the combination of BWT <3 mm and FC <50 mcg/g correctly classified 74% of patients with only 4.5% of patients falsely classified as not having endoscopic recurrence. CONCLUSIONS: A noninvasive approach combining bowel ultrasound and FC can be used with confidence for detecting POR in patients with CD without the requirement for CS.

The widespread diffusion of the coronavirus disease 2019 (COVID-19) has been one of the most dramatic challenges for health-care systems worldwide. Because of the huge number of symptomatic patients requiring hospitalization and intensive care treatment for severe COVID-19, most hospitals had to reset their priorities and to adapt their clinical activities to the management of patients affected by COVID-19. Several units have been reconverted into COVID-19 facilities, requiring the recruitment of medical and nursing staff taken from both medical and surgical departments; this rapid reorganization of service provision has led to a significant impact on daily health care for patients affected by other medical conditions, particularly patients with chronic diseases requiring long-term regular use of health-care resources. In Italy, a substantial change of practice has been recorded in most Gastroenterology Units through the entire country: although urgent and emergent services have been generally guaranteed, outpatient consultations, endoscopic and ultrasound procedures have been significantly reduced and limited to urgencies and oncologic indications [1Maida M. Sferrazza S. Savarino E. et al.Impact of the COVID-19 pandemic on gastroenterology divisions in Italy: a national survey.Dig Liver Dis. 2020; 52: 808-815Abstract Full Text Full Text PDF PubMed Scopus (47) Google Scholar]. The restructuring of clinical activities also affected inflammatory bowel disease (IBD) units, most of them temporarily stopped and postponed non-urgent activities and implemented virtual follow-up clinics (telemedicine, phone calls and/or Email consultation) in order to reduce the risk of viral transmission while maintaining the minimum standard of IBD care [2Saibeni S. Scucchi L. Dragoni G. et al.Activities related to inflammatory bowel disease management during and after the coronavirus disease 2019 lockdown in Italy: how to maintain standards of care.United European Gastroenterol J. 2020; 8: 1228-1235Crossref PubMed Scopus (15) Google Scholar]. Little is known about the potential impact of these restructuring activities on IBD-related outcomes such as risk of flare, complications, hospitalization or surgery. Emerging data suggest a potential collateral damage caused by the COVID-19 pandemic because of a decline in seeking medical attention and/or hospital admissions from several other conditions. A reduced rate of hospital admissions for acute coronary syndrome during Covid-19 outbreak has been reported in northern Italy as well as in the United States [3De Filippo O. D'Ascenzo F. Angelini F. et al.Reduced rate of hospital admissions for ACS during Covid-19 outbreak in Northern Italy.N Engl J Med. 2020; 383: 88-89Crossref PubMed Scopus (798) Google Scholar,4Solomon M.D. McNulty E.J. Rana J.S. et al.The Covid-19 pandemic and the incidence of acute myocardial infarction.N Engl J Med. 2020; 383: 691-693Crossref PubMed Scopus (520) Google Scholar] and an inflation in acute cardiovascular deaths, not related to COVID-19 infection, has been reported, probably because patients were not promptly referred to hospital during the pandemic [5Wu J. Mamas M.A. Mohamed M.O. et al.Place and causes of acute cardiovascular mortality during the COVID-19 pandemic.Heart. 2021; 107: 113-119Crossref PubMed Scopus (127) Google Scholar]. Moreover, a reduction in the number of patients diagnosed with various gastro-intestinal cancers has been reported as a consequence of the substantial drop in endoscopy services [6Lui T.K.L. Leung K. Guo C.G. et al.Impacts of the coronavirus 2019 pandemic on gastrointestinal endoscopy volume and diagnosis of gastric and colorectal cancers: a population-based study.Gastroenterology. 2020; 159: 1164-1166Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar,7Khan A. Bilal M. Morrow V. et al.Impact of the coronavirus disease 2019 pandemic on gastrointestinal procedures and cancers in the United States: a multicenter research network study.Gastroenterology. Mar 2021; ([Epub ahead of print])https://doi.org/10.1053/j.gastro.2021.02.055Abstract Full Text Full Text PDF Scopus (24) Google Scholar]; an increase in cancer deaths because of delay in diagnosis and screening procedures is expected in the near future [8Maringe C. Spicer J. Morris M. et al.The impact of the COVID-19 pandemic on cancer deaths due to delays in diagnosis in England, UK: a national, population-based, modelling study.Lancet Oncol. 2020; 21: 1023-1034Abstract Full Text Full Text PDF PubMed Scopus (1100) Google Scholar,9Ricciardiello L. Ferrari C. Cameletti M. et al.Pandemic on colorectal cancer screening delay: effect on stage shift and increased mortality.Clin Gastroenterol Hepatol. Sep 2020; ([Epub ahead of print])https://doi.org/10.1016/j.cgh.2020.09.008Abstract Full Text Full Text PDF PubMed Scopus (79) Google Scholar]. We aimed to investigate if the reorganization of our IBD Unit and resetting clinical activities during the lockdown period has had an impact on IBD-related outcomes in the post lockdown phase. Our IBD Unit cares for 2500 patients; a dedicated outpatient clinic, including first visits and scheduled follow up visits, takes place every day of the week. An operational room for the administration of biotechnological drugs and dedicated endoscopic sessions are also available. Our Gastroenterology ward includes 16 beds for patients with any gastroenterological disease referred by the Emergency Room, outpatients clinics or other hospitals. IBD patients who require hospitalization for acute, severe disease, can be admitted directly to the gastroenterology ward. Finally, a dedicated phone line is available to allow patients direct contact with the IBD medical staff if necessary. We have compared our IBD Unit activities (number of outpatients visits and endoscopies) performed during lockdown (March 2020 to May 2020) with the same period of the previous year. Then we have analyzed outpatients visits in the 7 months post lockdown period (June to December 2020) comparing these data with the same period of 2019. Month by month, we have classified patients in: 1) clinical remission; 2) mild disease activity; 3) moderate disease activity; and 4) severe disease activity, according to treatment decisions during each visit: no therapeutic changes = clinical remission; new prescription of aminosalicylates or aminosalicylates optimization = mild disease activity; prescription of systemic or low bioavailability steroids = moderate disease activity; new prescription of immunomodulators (IMMs) or biologics, biologic dose intensification or switch, hospital admission or surgical procedure = severe disease activity. Differences in the distribution of disease activity between the two periods in 2020 and 2019 have been analyzed using the chi square test. During lockdown outpatients follow up visits have been reduced by 37% compared to the same period in 2019 (405 vs 639). Elective endoscopic procedures have been reduced by 54.5% in the same period compared to 2019 (Fig. 1). Conversely, all patients receiving biologic therapies (both intravenous and subcutaneous) were regularly evaluated at scheduled intervals and scheduled infusions were maintained with no delay. Patients requiring hospitalization were regularly admitted to our gastroenterology ward. The decision of postponing follow up visits or endoscopic procedures was made on a case-by-case basis after a phone contact with the patient in which symptoms, laboratory tests and adherence to treatment were accurately assessed and recorded. In the 7 months post lockdown our IBD unit activity gradually returned toward normality; the number of follow up visits (1368 visits performed in 627 patients) was similar to the same period in 2019 (1329 visits performed in 636 patients). The distribution of disease activity month by month is shown in Fig. 2. No difference is observed compared to the same period of 2019. Although in August 2020, compared to August 2019, we have observed a significantly higher proportion of patients with active disease requiring escalation of therapy (38.3% vs 22.2%; p = 0.01), most of these patients had mild disease activity requiring only aminosalicylates optimization; no significant difference is observed in the proportion of patients with moderate to severe disease activity (23.4% vs 14.8%; p = 0.1). Compared to 2019, no significant differences have been observed in the number of urgent hospitalizations (46 vs 36; p = 0.2) or surgeries (22 vs 17; p = 0.3)Fig. 2Distribution of disease activity month by month in the post lockdown period and in the corresponding period in 2019.View Large Image Figure ViewerDownload Hi-res image Download (PPT) In summary, in our experience, restructuring clinical activities during lockdown had no significant impact on IBD clinical outcomes in the post lockdown phase. Some considerations can help to explain our results. The first one is how we have reset our priorities without reducing the level of care below acceptable standards for IBD patients. According to our Regional Health AuthoritY, during the lockdown period, in order to reduce the risk of transmission, outpatients' visits had to be limited only to those considered "urgent" according to the priorities code of the Italian health system (i.e. requiring medical assistance within 72 h or 10 days). In our opinion, these strict "urgency criteria" do not perfectly fit all IBD patients especially in the light of recent medical strategies such as early intervention, treat-to target and tight monitoring approaches [10Pugliese D. Papi C. Privitera G. et al.The management of inflammatory bowel diseases in the era of COVID-19 pandemic: when "non-urgent" does not mean "deferrable".Dig Liver Dis. 2020; 52: 1238-1240Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar]. According to this point of view, many "non urgent" interventions have been considered not deferrable and were regularly done. For example, patients in clinical remission ("non urgent" by definition) but requiring prompt evaluation and tight follow-up for planning long-term strategies have been regularly evaluated in a face-to-face setting. Secondly, we have implemented virtual follow-up using phone calls with a tailored approach. In fact, the decision of postponing follow up visits or endoscopic procedures was made on strict case by case criteria, after evaluation of symptoms, laboratory tests and adherence to treatment and taking into account the general course of the disease in individual patients. This approach allowed us to reschedule all procedures (visits or endoscopies) only in low-risk patients without negative impact on IBD-related outcomes. To our knowledge this is the first experience exploring the impact of restructuring an IBD unit during pandemic on IBD-related outcomes in the post lockdown period. The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Fabiola De Biasio: none Annalisa Aratari: None Stefano Festa has received consultancy fees and/or educational grants from Takeda, Sofar, Janssen Cilag Abbvie, Zambon. Roberto Lorenzetti: none Claudio Papi has received consultancy fees and/or educational grants from Abbvie, MSD, Takeda, Pfizer, Janssen-Cilag, Chiesi, Sofar, Ferring and Zambon. No other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The peak of incidence of inflammatory bowel disease (IBD) overlaps with the peak of reproductive age. Moreover, women affected by IBD are often concerned with the possible negative effects of their disease and medications on pregnancy and birth outcomes. From a physician point of view, managing IBD in pregnancy is challenging. Disease activity is the major cause of poor pregnancy outcomes and, therefore, achieving and maintaining IBD remission for the whole duration of pregnancy is the main therapeutic goal. The challenges in selecting therapy lie in balancing the proven efficacy of each drug with the level of safety uncertainty. Except for methotrexate and thalidomide, for which it exits an absolute contraindication in pregnancy, the evidence actually available suggest that most medications can be safely used during pregnancy if appropriately prescribed. The risks associated with drug withdrawal may be higher than the known risks of the medications themselves on pregnancy outcomes. However, all the decisions should be shared with the patient, all available information should be discussed and any therapeutic strategy must be tailored according to patient's context, including disease pattern, activity, severity and acceptance of risk.

AbstractBackgroundThe long‐term course of ulcerative colitis after a severe attack is poorly understood. Second‐line rescue therapy with cyclosporine or infliximab is effective for reducing short‐term colectomy but the impact in the long‐term is controversial.ObjectiveThe purpose of this study was to evaluate the long‐term course of acute severe ulcerative colitis patients who avoid early colectomy either because of response to steroids or rescue therapy.MethodsThis was a multicentre retrospective cohort study of adult patients with acute severe ulcerative colitis admitted to Italian inflammatory bowel disease referral centres from 2005 to 2017. All patients received intravenous steroids, and those who did not respond received either rescue therapy or colectomy. For patients who avoided early colectomy (within 3 months from the index attack), we recorded the date of colectomy, last follow‐up visit or death. The primary end‐point was long‐term colectomy rate in patients avoiding early colectomy.ResultsFrom the included 372 patients with acute severe ulcerative colitis, 337 (90.6%) avoided early colectomy. From those, 60.5% were responsive to steroids and 39.5% to the rescue therapy. Median follow‐up was 44 months (interquartile range, 21–85). Colectomy‐free survival probability was 93.5%, 81.5% and 79.4% at 1, 3 and 5 years, respectively. Colectomy risk was higher among rescue therapy users than in steroid‐responders (log‐rank test, p = 0.02). At multivariate analysis response to steroids was independently associated with a lower risk of long‐term colectomy (adjusted odds ratio = 0.5; 95% confidence interval, 0.2–0.8), while previous exposure to antitumour necrosis factor‐α agents was associated with an increased risk (adjusted odds ratio = 3.0; 95% confidence interval, 1.5–5.7). Approximately 50% of patients required additional therapy or new hospitalisation within 5 years due to a recurrent flare. Death occurred in three patients (0.9%).ConclusionsPatients with acute severe ulcerative colitis avoiding early colectomy are at risk of long‐term colectomy, especially if previously exposed to antitumour necrosis factor‐α agents or if rescue therapy during the acute attack was required because of steroid refractoriness.

We have read with interest the article of Zingone et al. "Screening for active COVID-19 infection and immunization status prior to biologic therapy in IBD patients at the time of the pandemic outbreak" recently published on Digestive and Liver Disease [1]. The authors, using a pragmatic approach, suggest updating the screening commonly recommended prior to the beginning of biological therapy in Inflammatory Bowel Disease (IBD) patients, adding SARS-CoV-2 RT-PCR and, when available, antibody testing.