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Objective: In patients with Crohn's disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn's disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse (>6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn's Disease Patients in Sustained Steroid-free Remission on Combination Therapy)., Design: In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE)., Results: In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting short-term (0.76-0.80 vs 0.74 vs 0.71 vs 0.69, respectively) and mid/long-term relapse (0.66-0.68 vs 0.61 vs 0.52 vs 0.59, respectively)., Conclusion: In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal., Trial Registration Number: NCT00571337 and NCT02177071., Competing Interests: Competing interests: PB has received research grants from AbbVie, Amgen, Celltrion, Mylan, Pfizer and Takeda; lecture fees from AbbVie, Celltrion, Janssen, Lilly and Takeda; and consulting fees from AbbVie, Arena Pharmaceuticals, Bristol Myers Squibb, Celltrion, Dr Falk Pharma, Galapagos, Janssen, Lilly, Pentax, PSI-CRO, Roche, Takeda and Tetrameros. LV has received fees from AbbVie, Amgen, Biogen, Mylan, Takeda, MSD, Janssen, Pfizer, Ferring and Galapagos. SV has received speaker’s fees from AbbVie, Ferring, Janssen and Takeda. J-FC has received grants from AbbVie, Janssen Pharmaceuticals, Prometheus, Takeda and Bristol Myers Squibb; receiving payment for lectures from AbbVie, and Takeda; receiving consulting fees from AbbVie, Amgen, AnaptysBio, Allergan, Arena Pharmaceuticals, Boehringer Ingelheim, Bristol Myers Squibb, Celgene Corporation, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Galmed Research, Glaxo Smith Kline, Genentech (Roche), Janssen Pharmaceuticals, Kaleido Biosciences, Immunic, Invea, Iterative Scopes, Merck, Landos, Microba Life Science, Novartis, Otsuka Pharmaceutical, Pfizer, Protagonist Therapeutics, Prometheus, Sanofi, Seres, Takeda, Teva, TiGenix, Vifor; and hold stock options in Intestinal Biotech Development. EL has received educational and research grants from Janssen, Pfizer, AbbVie and Takeda, Fresenius-Kabi; speaker fees from AbbVie, Dr Falk Pharma, Ferring, Janssen, Pfizer, Celgene, Bristol Myers Squibb (BMS), Galapagos and Takeda; advisory board fees for AbbVie, Celgene, Ferring, Janssen, BMS, Pfizer, Takeda, Gilead-Galapagos, Arena and Elli Lilly; and consultancy fees from AbbVie., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Study Aims: Monitoring the symptoms of inflammatory bowel diseases (IBD) patients is now frequently made in the form of patient reported outcomes (PRO), rather than historical clinical activity scores. Unlike several chronic diseases, the role of telemonitoring in IBD has not yet been defined, particularly in terms of patient compliance with remote monitoring; the aim of our study was to assess patient compliance with digital monitoring of PRO as part of routine medical follow-up., Patients and Methods: we performed a monocentric prospective study in the Gastroenterology Unit of Liège's University Hospital between May 2023 and February 2024. Adherence was considered optimal if 50% of the recordings planned for the duration of the follow-up were carried out., Results: 31% of the patients included achieved at least 50% total encoding of their PRO over the 9 months of follow-up. The main cause of failure cited by patients was technical difficulties, well ahead of poor motivation. The overall satisfaction of practitioners and patients was generally good. Male gender was the only factor associated with adherence., Conclusion: Overall adherence to PRO telemonitoring in IBD was around 40% and was mainly impaired by technical difficulties. Despite this, both patients and healthcare professionals found this type of monitoring relevant., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

Introduction: Ulcerative colitis is a chronic inflammatory bowel disease, affecting the colorectal mucosae, with a relapsing-remitting course, characterized by the trafficking and gathering of lymphocytes in the inflammatory intestinal mucosa. Sphingosine-1-phosphate (S1P) receptor modulators preventing lymphocytes egress from lymphoid tissues to the active inflammation site is an alternative therapeutic option in this condition., Area Covered: We carried out a comprehensive review of the literature available on Medline, Scopus and Embase regarding the pharmacokinetics of S1P receptor modulators. For each compound, we reviewed the mechanism of action, pharmacokinetic data and efficacy and safety data from phase 3 studies and real-life studies when available., Expert Opinion: S1P receptor modulators, including ozanimod and etrasimod (both currently on the market) as well as VTX002 (under development), are a new class of drugs for the treatment of moderate to severe ulcerative colitis, inducing and maintaining the remission. Due to its pharmacokinetic features, this class of drugs has certain advantages such as an oral administration, a short half-life, a high volume of distribution, and no immunogenicity. On the other hand, there are risks of cardiological and ophthalmological side-effects, as well as drug-drug interactions risk, that require special attention from the healthcare providers.

Introduction: Patients with ulcerative colitis (UC) receiving immunosuppressive drugs are at substantial risk of colectomy. We aimed to assess the risk of postoperative complications of tofacitinib exposure before colectomy in comparison with biologics., Methods: A multicenter, retrospective, observational study was conducted in patients with UC who underwent total colectomy for medically refractory disease, exposed to tofacitinib or a biologic before surgery. Primary outcome was the occurrence of any complication within 30 (early) and 90 (late) days after surgery. Secondary outcomes were the occurrence of infections, sepsis, surgical site complications, venous thromboembolic events (VTE), hospital readmissions, and redo surgery within the same timepoints., Results: Three hundred one patients (64 tofacitinib, 162 anti-tumor necrosis factor-α agents, 54 vedolizumab, and 21 ustekinumab) were included. No significant differences were reported in any outcome, except for a higher rate of early VTE with anti-tumor necrosis factor-α agents ( P = 0.047) and of late VTE with vedolizumab ( P = 0.03). In the multivariate analysis, drug class was not associated with a higher risk of any early and late complications. Urgent colectomy increased the risk of any early (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.06-3.48) complications, early hospital readmission (OR 4.79, 95% CI 1.12-20.58), and early redo surgery (OR 7.49, 95% CI 1.17-47.85). A high steroid dose increased the risk of any early complications (OR 1.96, 95% CI 1.08-3.57), early surgical site complications (OR 2.03, 95% CI 1.01-4.09), and early redo surgery (OR 7.52, 95% CI 1.42-39.82). Laparoscopic surgery decreased the risk of any early complications (OR 0.54, 95% CI 0.29-1.00), early infections (OR 0.39, 95% CI 0.18-0.85), and late hospital readmissions (OR 0.34, 95% CI 0.12-1.00)., Discussion: Preoperative tofacitinib treatment demonstrated a postoperative safety profile comparable with biologics in patients with UC undergoing colectomy., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

At a clinical level, ileal and colonic Crohn's disease (CD) are considered as separate entities. These subphenotypes need to be better supported by biological data to develop personalised medicine in CD. To this end, we combined different technologies (proximity extension assay, selected reaction monitoring, and high-sensitivity turbidimetric immunoassay (hsCRP)) to measure 207 immune-related serum proteins in CD patients presenting no endoscopic lesions (endoscopic remission) (n = 23), isolated ileal ulcers (n = 17), or isolated colonic ulcers (n = 16). We showed that isolated ileal ulcers and isolated colonic ulcers were specifically associated with 6 and 18 serum proteins, respectively: (high level: JUN, CNTNAP2; low level: FCRL6, LTA, CLEC4A, NTF4); (high level: hsCRP, IL6, APCS, CFB, MBL2, IL7, IL17A, CCL19, CXCL10, CSF3, IL10, CLEC4G, MMP12, VEGFA; low level: CLEC3B, GSN, TNFSF12, TPSAB1). Isolated ileal ulcers and isolated colonic ulcers were detected by hsCRP with an area under the receiver operating characteristics curve of 0.64 (p-value = 0.07) and 0.77 (p-value = 0.001), respectively. We highlighted distinct serum proteome profiles associated with ileal and colonic ulcers in CD, this finding might support the development of therapeutics and biomarkers tailored to disease location. SIGNIFICANCE: Although ileal and colonic Crohn's disease present important clinical differences (eg, progression, response to treatment and reliability of biomarkers), these two entities are managed with the same therapeutic strategy. The biological specificities of ileal and colonic Crohn's disease need to be better characterised to develop more personalised approaches. The present study used robust technologies (selected reaction monitoring, proximity extension assays and turbidimetric immunoassay) to quantify precisely 207 serum immune-related proteins in three groups of Crohn's disease patients presenting: 1) no endoscopic lesions (endoscopic remission) (n = 23); 2) isolated ileal ulcers (n = 17); 3) isolated colonic ulcers (n = 16). We found distinct serum proteome signatures associated with ileal and colonic ulcers. Our findings could foster the development of biomarkers and treatments tailored to Crohn's disease location., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Aims: Data regarding the effectiveness and safety of Janus kinase [JAK] inhibitors and sphingosine-1-phosphate [S1P] receptor modulators in antibiotic refractory chronic pouchitis [CARP] are lacking., Methods: This ECCO-CONFER project retrospectively collected data for JAK inhibitor or S1P receptor modulator treatments for CARP with at least 3 months of follow-up. The outcomes included corticosteroid- and antibiotic-free clinical response and remission at 3 and 12 months, and trends in modified pouchitis disease activity index [mPDAI], endoscopic PDAI, C-reactive protein, and calprotectin., Results: Seventeen treatments in 15 patients were evaluated. Previous pouchitis treatments included infliximab [5/15], adalimumab [4/15], vedolizumab [9/15], and ustekinumab [5/15]. Pooling data on JAK inhibitors [eight tofacitinib, one filgotinib, and six upadacitinib] after 3 months [T3], steroid- and antibiotic-free clinical response was achieved in 53.3% [8/15], and steroid- and antibiotic-free clinical remission was achieved in 40% [6/15]. Of the patients with at least 12 months of follow-up, steroid- and antibiotic-free clinical response was achieved in 50% [3/6] and remission in one patient [16.7%], endoscopic response in 50% [3/6], and endoscopic remission in 50% [3/6]. Of the two ozanimod treatments at T3, steroid- and antibiotic-free clinical response was achieved in one patient, without remission; both discontinued ozanimod before T12. No side effects were reported., Conclusions: Small molecules may represent a suitable option for CARP refractory to multiple biologics, deserving further investigation., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Recruitment for randomized controlled trials [RCTs] in inflammatory bowel diseases [IBD] has substantially dropped over time. This study aimed to assess reasons why IBD patients are not included in sponsored multicentre phase IIb-III RCTs., Methods: All IOIBD members [n = 58] were invited to participate. We divided barriers to participation as follows: [1] reasons patients with active IBD were not deemed appropriate for an RCT; [2] reasons qualified patients did not wish to participate; and [3] reasons for screen failure [SF] in patients agreeing to participate. We assess these in a 4-week prospective study including, consecutively, all patients with symptomatic disease for whom a treatment change was required. In addition, we performed a 6-month retrospective study to further evaluate reasons for SF., Results: A total of 106 patients (60 male [56.6%], 63 Crohn's disease [CD] [59.4%]), from ten centres across the world, were included in the prospective study. An RCT has not been proposed to 65 of them [mainly due to eligibility criteria]. Of the 41 patients to whom an RCT was offered, eight refused [mainly due to reluctance to receive placebo] and 28 agreed to participate. Among these 28 patients, five failed their screening and 23 were finally included in an RCT. A total of 107 patients (61 male [57%], 67 CD [62.6%]), from 13 centres worldwide, were included in our retrospective study of SFs. The main reason was insufficient disease activity., Conclusion: This first multicentre study analysing reasons for non-enrolment in IBD RCTs shows that we lose patients at each step. Eligibility criteria, the risk of placebo assignment, and insufficient disease activity were part of the main barriers., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Inflammatory bowel disease [IBD] is associated with an increased risk of developing lymphoma. Although recent data have clarified the epidemiology of lymphoma in IBD patients, the clinical and pathological characteristics of lymphoma in IBD remain poorly known., Methods: Patients with IBD and lymphoma were retrospectively identified in the framework of a national collaborative study including the Groupe d'Étude Thérapeutique des Affections Inflammatoires du Tube Digestif [GETAID] and the Lymphoma Study Association [LYSA]. We characterized clinical and prognostic features for the three most frequent lymphoma subtypes occurring in IBD. We performed a multicentre case-control study. Controls [lymphoma de novo] were matched [5:1] to cases on gender, age at diagnosis, lymphoma subtype, year of diagnosis, and IPI/FLIPI indexes. Overall survival and progression-free survival were compared between cases and controls., Results: In total, 133 IBD patients with lymphoma were included [males = 62.4%, median age at lymphoma diagnosis = 49 years in males; 42 years in females]. Most had Crohn's disease [73.7%] and were exposed to thiopurines [59.4%]. The most frequent lymphoma subtypes were diffuse large B cell lymphoma [DLBCL, 45.1%], Hodgkin lymphoma [HL, 18.8%], and follicular lymphoma [FL, 10.5%]. When matched with 365 controls, prognosis was improved in IBD patients with DLBCL compared to controls [p = 0.0064, hazard ratio = 0.36] or similar [HL and FL]., Conclusions: Lymphomas occurring in IBD patients do not seem to have a worse outcome than in patients without IBD. Due to the rarity of this situation, such patients should be managed in expert centres., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: While the efficacy of tofacitinib to induce and maintain clinical and endoscopic remission is well established in ulcerative colitis (UC), little is known about its efficacy to induce histological remission., Methods: We conducted a retrospective multicentric cohort study. UC patients ≥ 16 years treated by tofacitinib in whom histological activity has been evaluated before and after induction were eligible. The primary endpoint was the histological remission at the end of induction, assessed by the Nancy index and the epithelial neutrophilic infiltrate., Results: A total of 42 patients with UC (93% previously exposed to an anti-TNF and 81% to vedolizumab) were included between July 2018 and April 2022 and were followed for a median duration of 84 weeks [IQR, 35-134]. At the end of induction period (whether prolonged or not), 19% and 24% of patients achieved histological remission, using the Nancy index and the epithelial neutrophilic infiltrate, respectively. Survival without tofacitinib discontinuation was significantly longer in patients without epithelial neutrophilic infiltrate at the end of induction (whether prolonged or not) compared with patients with epithelial neutrophilic infiltrate (p = 0.036)., Conclusion: Tofacitinib induced histological remission in one fifth to one quarter of patients with UC who have previously failed anti-TNF or/and vedolizumab after induction (whether prolonged or not)., Competing Interests: Conflict of interests S Vieujean lecture and/or consulting fees from Abbvie, Ferring, Janssen, Takeda. D Laharie counselling, boards, transports and/or fees from Abbvie, Biogaran, Biogen, Ferring, HAC-pharma, Janssen, MSD, Novartis, Pfizer, Prometheus, Roche, Takeda, Theradiag, Tillots. A Buisson received consulting fees from AbbVie, Amgen, Arena, Biogen, Celltrion Healthcare, CTMA, Galapagos, Janssen, MSD, Nexbiome, Pfizer, Roche, Takeda, and Tillotts; and lecture fees from AbbVie, Amgen, Biogen, Galapagos, Janssen, Mayoli-Spindler, MSD, Norgine, Pfizer, Roche, Takeda, Tillotts, and Vifor Pharma. X Roblin served as a speaker, a consultant, and/or an advisory board member for MSD, Pfizer, Celltrion, Janssen, Takeda, AbbVie, Amgen, Biogen, Galapagos, Roche, and Theradiag. M Fumery declares financial support from Abbvie, MSD, Ferring, Boehringer, Pfizer, Takeda, Biogen, Amgen, Gilead, Sandoz, Celgene, Galapagos, Janssen, and Tillots Pharma. S Nancey declares lecture and/or consulting fees from Abbvie, Janssen, Ferring, Takeda, Amgen, Biogen, Novartis, Celltrion, Pfizer, MEDAC, NORDIC Pharma, Maat Pharma. P Wils declares lecture and/or consulting fees from Abbvie, Ferring, Biogen, Janssen, Celltrion, Takeda. R Altwegg declares counselling, boards, transports or fees from Abbvie, Amgen, Biogen, Ferring, Janssen, MSD, Pfizer, Takeda, Tillotts. L Seidel has no conflict of interest. B Caron declares lecture and/or consulting fees from Abbvie, Amgen, Celltrion, Ferring, Janssen, Lilly, and Takeda. L Peyrin-Biroulet declares consulting fees from AbbVie, Adacyte, Alimentiv, Alma Bio Therapeutics, Amgen, Applied Molecular Transport, Arena, Biogen, BMS, Celltrion, CONNECT Biopharm, Cytoki Pharma, Enthera, Ferring, Fresenius Kabi, Galapagos, Genentech, Gilead, Gossamer Bio, GSK, HAC-Pharma, IAG Image Analysis, Index Pharmaceuticals, Inotrem, Janssen, Lilly, Medac, Mopac, Morphic, MSD, Norgine, Nordic Pharma, Novartis, OM Pharma, ONO Pharma, OSE Immunotherapeutics, Pandion Therapeutics, Par'Immune, Pfizer, Prometheus, Protagonist, Roche, Sanofi, Sandoz, Takeda, Theravance, Thermo Fisher, Tigenix, Tillots, Viatris, Vifor, Ysopia, Abivax, Samsung, Ventyx, Roivant, Vectivbio., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background: The inactive dephosphorylated and uncarboxylated form of the matrix Gla protein (dp-ucMGP) has been shown to be increased in plasma of inflammatory bowel disease (IBD) patients. Our aim was to assess if the plasmatic level of dp-ucMGP could reflect disease endoscopic activity, presence of strictures and cumulative structural bowel damage in Crohn's disease (CD) patients., Methods: The plasmatic level of dp-ucMGP was measured in a monocentric cohort of prospectively recruited patients. The analysis was done by chemiluminescent immunoassay on blood samples collected the day of a planned ileocolonoscopy. In addition to classical clinical data (gender, age, body mass index (BMI), disease duration, current treatment), endoscopic data (disease location, Crohn's Disease Endoscopic Index of Severity (CDEIS), mucosal healing (MH), presence of 9 CD lesion types) and biological markers (faecal calprotectin and C-reactive protein (CRP)) were collected. The association between dp-ucMGP level and Lémann index was also investigated. Univariate linear regression was used to investigate the relationship between dp-ucMGP level and different parameters collected., Results: A total of 82 ileocolonoscopies and dp-ucMGP assays were performed in 75 CD patients (45 females; 37 ileocolonic, 19 ileal and 19 colonic diseases) between October 2012 and November 2019. A total of 24 patients (29.3%) showed MH. The dp-ucMGP levels were not associated with MH, CDEIS, faecal calprotectin or CRP levels. Plasmatic dp-ucMGP levels increased significantly with age ( p  = 0.0032), disease duration ( p  = 0.0033), corticosteroids use ( p  = 0.019) and tended to increase in patients with intestinal strictures ( p  = 0.086) but not with the Lémann index., Conclusion: The significant increase of plasmatic dp-ucMGP levels with age, disease duration and the trend observed in patients with non-ulcerated strictures may suggest that this extracellular matrix protein could be a marker of tissue remodelling and physiological ageing of the gut.

Background and Aims: Confocal endomicroscopy is a technique allowing the in vivo assessment of the superficial layers of the mucosa. Preliminary studies have already suggested its added value in the assessment of endoscopic remission in inflammatory bowel disease. However, most of these studies were performed on patients still having incomplete mucosal healing. Our aim was to disclose persisting endomicroscopic anomalies in patients with full endoscopic remission and to compare them between vedolizumab- and anti-tumor necrosis factor-treated patients., Methods: We screened patients with Crohn's disease (CD) or ulcerative colitis (UC) treated for more than 6 months with biologic therapy, and being in steroid-free clinical and biological remission. White light endoscopy and probe-based confocal laser endomicroscopy (pCLE) analysis were performed in the ileum, right colon, transverse colon, left colon, and rectum. Full endoscopic remission was defined by a Mayo endoscopic score of 0 in UC and no remaining ulcer or erosion in CD. Patients were prospectively followed up and clinical relapses were recorded., Results: Seventy-two CD and UC patients treated by biologic therapy and in clinical and biological remission were screened. A total of 37 were also in full endoscopic remission and were included in our study; 183 intestinal segments were analyzed. We found residual pCLE anomalies in most of the patients. These anomalies were not significantly associated with any demographic or clinical characteristic including the treatment received, nor were they associated with histological parameters, levels of C-reactive protein or fecal calprotectin. Among the 37 patients, 7 (18.9%) relapsed over a median follow-up of 33.7 months. The risk of relapse was not associated with any clinical, biological, histologic, or pCLE feature at baseline., Conclusion: Despite endoscopic, biological, and even histological remission, we found a high prevalence of endomicroscopic abnormalities, which were not different between anti-tumor necrosis factor- and vedolizumab-treated patients. The clinical significance of these anomalies remains to be clarified., (© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The gut microbiota play a pivotal role in human health. Dysbiosis, alterations in microbiota composition and function, is associated with gastrointestinal disorders, including inflammatory bowel disease (IBD). This international survey aimed to assess physicians' experiences, perceptions, and practices related to microbiome modulation for gastrointestinal conditions, with a focus on IBD. Results from 142 healthcare professionals, predominantly gastroenterologists, confirmed a consensus on the relevance of the gut microbiota in IBD pathogenesis. However, the utilization of microbial composition analysis and probiotics in clinical practice was limited, primarily due to the lack of standardized guidelines and supporting evidence. Physicians held conflicting views on antibiotics, recognizing their potential for inducing remission but also causing flares in IBD. Respondents also had varying opinions on the efficacy of fecal microbiota transplantation (FMT) for different gastrointestinal conditions, with higher confidence in FMT effectiveness for irritable bowel syndrome with diarrhea, pouchitis, and ulcerative colitis. Concerns on FMT included uncertainty about effect duration, administration intervals, and conflicting evidence. Donor selection was believed to be a crucial factor in FMT outcomes. This survey highlights the need for further research and evidence-based guidelines to optimize the use of microbiome-based therapies in clinical practice. As our understanding of the gut microbiome continues to evolve, these insights will contribute to more informed and personalized approaches to managing gastrointestinal disorders.

In Crohn's disease, the treat-to-target strategy has been greatly encouraged and has become a standard of care. In this context, defining the target [remission] constitutes a major stake and is fuelling the literature. Currently, clinical remission [symptom control] is no longer the only objective of treatments since it does not allow to closely control inflammation-induced tissue damage. The introduction of endoscopic remission as a therapeutic target clearly represented progress but this examination remains invasive, costly, not well accepted by patients and does not allow tight control of disease activity. More fundamentally, morphological techniques [e.g. endoscopy, histology, ultrasonography] are limited since they do not evaluate the biological activity of the disease but only its consequences. Besides, emerging evidence suggests that biological signs of disease activity could better guide treatment decisions than clinical parameters. In this context, we stress the necessity to define a novel treatment target: biological remission. Based on our previous work, we propose a conceptual definition of biological remission which goes beyond the classical normalization of inflammatory markers [C-reactive protein and faecal calprotectin]: absence of biological signs associated with the risk of short-term relapse and mid-/long-term relapse. The risk of short-term relapse seems essentially to be characterized by a persistent inflammatory state while the risk of mid-/long-term relapse implies a more heterogeneous biology. We discuss the value of our proposal [guiding treatment maintenance, escalation or de-escalation] but also the fact that its clinical implementation would require overcoming major challenges. Finally, future directions are proposed to better define biological remission., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Crohn's disease (CD) mostly affects the terminal ileum and ileocecal region and up to 80% of patients end up requiring surgery. Previously reserved for complicated or refractory forms, surgery is now considered as an alternative to medical treatment in localized ileocecal disease., Areas Covered: This review examines factors associated with response to medical treatment and those associated with the need for surgery in ileocecal CD to identify the patients' profile for whom pharmacotherapy might be enough. Factors associated with the recurrence and the postoperative complications are also reviewed to help the clinician identify patients for whom medical therapy might be preferred., Expert’s Opinion: LIR!C study long-term follow-up data show that 38% of infliximab-treated patients were still treated with infliximab at the end of their follow-up, while 14% had switched to another biologic or had received immunomodulator or corticosteroid and 48% had CD-related surgery. Only the combination with an immunomodulator was associated with a greater likelihood of continuing infliximab. Patients with ileocecal CD for whom pharmacotherapy might be sufficient are probably those with no risk factors for CD-related surgery.In addition, patients with high risk of recurrence or of post-operative complications may benefit more from medical treatment than from surgery.

Background and Aims: Solid organ transplantation, with the exception of liver, has rarely been reported in patients affected by inflammatory bowel diseases [IBD]., Methods: This is an ECCO-CONFER project collecting cases of solid organ transplants [with the exclusion of liver] that were performed in IBD patients. We evaluated the change in the IBD therapy, need for bowel resection due to medically refractory IBD, or need for hospitalisation due to IBD relapse ['severe IBD course'] before and after transplantation., Results: in total, 34 organ transplantations [28 kidney, five heart, one lung] in 33 IBD patients were collected [67% male, 55% Crohn's disease, mean age 53 ± 16 years]. The median follow-up was 4.3 years (interquartile range [IQR] 3.2-10.7); 29 patients [87.9%] were treated with tacrolimus, 25 [76%] with systemic steroids, 22 [67%] with mycophenolate mofetil, 11 [33%] with everolimus, six with cyclosporine [18%]. One patient was treated with infliximab, two patients with adalimumab, two patients with vedolizumab, one patient with ustekinumab. Overall, a severe IBD course was observed in three [9.3%] patients before transplantation and in four [11.7%] in the post-transplant setting [p = 0.26]. Three cases of cancer [excluding skin non-melanoma] [9.1%] were recorded in the post-transplantation period versus two in the pre-transplantation period [6.1%, p = 0.04]. Six patients [18.2%] died during the period of observation. No deaths were associated with IBD or complications of the transplant., Conclusions: In IBD patients, solid organ transplantation does not seem to impact on the IBD severity. However, the risk of malignancy needs further investigation., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: Inflammatory bowel disease (IBD) can affect patients during their childbearing years. Literature evidence is scarce regarding the level of knowledge among health care professionals (HCPs) and patients about the impact of IBD on fertility. The aim of this survey was to investigate HCPs' and patients' knowledge on fertility, pregnancy, and sexual function, to evaluate how HCPs approach this topic and to report patients' reproductive outcomes., Methods: Subjects were invited to anonymously complete an online questionnaire collecting data on demographics, patients' disease characteristics, Crohn's and colitis pregnancy-specific disease-related knowledge (CCPKnow), family planning, reason of childlessness, pregnancy outcomes, need for assisted reproductive technology, impact on sexual function, and availability of patients' information regarding IBD and pregnancy., Results: A total of 257 HCPs from 40 countries and 793 patients (615 females, 176 males and 2 who preferred not to disclose their gender; 396 (50%) with ulcerative colitis, 381 (48%) with Crohn's disease, 14 (1.8%) with undetermined IBD) from 4 countries completed the survey. In total, 98.4% of HCPs had good or very good pregnancy-specific knowledge according to CCPKnow score, compared to only 29.3% of patients. Of the women surveyed, 56.3% had no children (14.1% due to a voluntary choice). A total of 427 pregnancies and 401 live births were reported in 266 women. Twenty-four pregnancies (5.6%) in 22 women required assisted reproductive technologies (ART). There were no more complications in pregnancies resulting from ART compared with spontaneous conception (5/24; 20.8% vs 81/401; 20.2%). Three quarters of IBD patients (75.6%) had breastfed. An impaired sexual function was found in one-fifth (21.9%) of men with IBD, while two-thirds (66.1%) of the women reported sexual function impairment. Surprisingly, 63% of patients reported not having received any information about IBD and pregnancy, and only 10% of patients had received information from their IBD specialist. In addition, 42.1% and 36% of HCPs had already referred a patients to a medically assisted reproduction center to receive general information about their reproductive health and about options of fertility preservation (e.g., cryopreservation), respectively., Conclusion: IBD patients have a poor knowledge about the impact of IBD on fertility and pregnancy and HCPs do not sufficiently inform their patients. More information on these topics is needed for IBD patients., Competing Interests: Conflict of interest S Vieujean declares no conflict of interest. M De Vos has received speaker fees from Ferring, Merck, Gedeon Richter, Organon and Cooper Surgical. F D'Amico has served as a speaker for Janssen, Galapagos, Sandoz, and Omega Pharma. R Dudkowiak declares no conflict of interest. S Danese has served as a speaker, consultant, and advisory board member for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring, Genentech, Grunenthal, Johnson and Johnson, Millenium Takeda, MSD, NikkisoEurope GmbH, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma and Vifor. L Peyrin-Biroulet : personal fees from Galapagos, AbbVie, Janssen, Genentech, Ferring, Tillots, Pharmacosmos, Celltrion, Takeda, Boerhinger Ingelheim, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma, Sterna, Nestle, Inotrem, Enterome, Allergan, MSD, Roche, Arena, Gilead, Hikma, Amgen, BMS, Vifor, Norgine ; Mylan, Lilly, Fresenius Kabi, Oppilan Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera, Theravance ; Pandion Therapeutics, grants from Abbvie, MSD, Takeda, Fresenius Kabi, stock options : CTMA., (Copyright © 2023 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Inflammatory bowel diseases (IBD) encompass two main entities including ulcerative colitis and Crohn's disease. Although having a common global pathophysiological mechanism, IBD patients are characterized by a significant interindividual heterogeneity and may differ by their disease type, disease locations, disease behaviours, disease manifestations, disease course as well as treatment needs. Indeed, although the therapeutic armamentarium for these diseases has expanded rapidly in recent years, a proportion of patients remains with a suboptimal response to medical treatment due to primary non-response, secondary loss of response or intolerance to currently available drugs. Identifying, prior to treatment initiation, which patients are likely to respond to a specific drug would improve the disease management, avoid unnecessary side effects and reduce the healthcare expenses. Precision medicine classifies individuals into subpopulations according to clinical and molecular characteristics with the objective to tailor preventative and therapeutic interventions to the characteristics of each patient. Interventions would thus be performed only on those who will benefit, sparing side effects and expense for those who will not. This review aims to summarize clinical factors, biomarkers (genetic, transcriptomic, proteomic, metabolic, radiomic or from the microbiota) and tools that could predict disease progression to guide towards a step-up or top-down strategy. Predictive factors of response or non-response to treatment will then be reviewed, followed by a discussion about the optimal dose of drug required for patients. The time at which these treatments should be administered (or rather can be stopped in case of a deep remission or in the aftermath of a surgery) will also be addressed. IBD remain biologically complex, with multifactorial etiopathology, clinical heterogeneity as well as temporal and therapeutic variabilities, which makes precision medicine especially challenging in this area. Although applied for many years in oncology, it remains an unmet medical need in IBD., Competing Interests: S Vieujean received speaker’s fees from Janssen, Takeda, Ferring and Abbvie. E Louis received research grant: Janssen, Pfizer, Ferring, Falk, Abbvie and Takeda; educational grant: AbbVie, Janssen, Fresenius-Kabi and Takeda; speaker fees: Abbvie, Falk, Ferring, Janssen, Pfizer, Galapagos and Takeda; advisory board: Abbvie, Celgene, Ferring, Janssen, BMS, Pfizer, and Takeda, Galapagos, Gilead, Arena, Elli Lilly; consultant: Abbvie, (© The Author(s), 2023.)

Introduction: Ustekinumab is a humanized monoclonal antibody, targeting the p40 subunit common to both human interleukin 12 and 23, approved by the European Medicines Agency and US Food and Drug Administration for the treatment of moderate-to-severe ulcerative colitis., Areas Covered: In this review, the results of the phase 3 UNIFI and the real-world studies assessing the efficacy and safety of ustekinumab in moderate-to-severe ulcerative colitis are discussed, as well as limitations of these studies. Predictive factors of response, the interest of therapeutic drug monitoring and the positioning of ustekinumab in specific situations are also addressed. Finally, in the light of data presented, the positioning of ustekinumab in the therapeutic algorithm of ulcerative colitis will also be considered., Expert Opinion: Ustekinumab has been shown to be effective to induce and maintain clinical, endoscopic and histologic remission in moderate-to-severe ulcerative colitis both in phase 3 and real-world studies, with a favorable safety profile. Overall, its favorable risk-benefit ratio, its efficacy on extra-intestinal manifestations and in biologics failure patients make ustekinumab an ideal candidate as first, second, or third-line therapy in ulcerative colitis.

Background: Patients with inflammatory bowel disease (IBD) consider that their diet is important for controlling symptoms and frequently ask their physician for additional guidance on this matter. The objectives of the present study of patients with IBD were to characterize the prevalence of exclusion diets and fasting and to identify associated risk factors., Methods: Using an anonymous questionnaire, we screened patients attending our IBD nutrition clinic between November 2021 and April 2022 for exclusion diets. The avoidance of a food category completely was defined as total exclusion and avoidance most of the time was defined as partial exclusion. We also asked patients whether they fasted totally, intermittently, or partially., Result: A total of 434 patients with IBD were included. On inclusion, 159 patients (36.6%) totally excluded at least one food category and 271 (62.4%) partially excluded at least one food. Intermittent, total, or partial fasting was reported by 30.8% of the patients. Disease activity (odds ratio (OR) [95% confidence interval] = 1.7 [1.1-2.7], p = 0.0130) and treatment with a small-molecule or an investigational drug (OR = 4.0 [1.5-10.6], p = 0.0059) were independently associated with an exclusion diet. A history of stenosis (OR = 2.0 [1.2-3.2], p = 0.0063) and active disease (OR = 1.9 [1.2-3.1], p = 0.0059) were associated with fasting., Conclusion: In this real-world study, approximately two-thirds of our patients with IBD reported the partial or total exclusion of at least one food category and one third reported fasting. A systematic nutritional evaluation might improve clinical management and quality of care for patients with IBD both Crohn's disease and ulcerative colitis., (© 2023 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Background: Treatment choices for patients with inflammatory bowel disease (IBD) are based on the balance between risks and benefits. Our AI was to compare the perspectives of patients and physicians in evaluating the risks and benefits before initiating therapy for IBD., Methods: An anonymous survey was conducted between March and August 2022. All patients with confirmed IBD and all physicians who attended an IBDscope webinar were invited to participate., Results: In total, 367 patients and 146 physicians participated. For most patients (71.4%) and physicians (89.0%), efficacy and safety were equally important. Clinical improvement and clinical remission were the most relevant outcomes for patients (90.9 and 88.4), while clinical remission and endoscopic remission were for physicians (90.0 and 87.6). The main factors in the benefit-risk assessment were quality of life (95.1%), disease activity (87.5%), and presence of comorbidities (84.5%) for patients, and presence of comorbidities (99.3%), disease activity (97.9%), and prior failure to biologics/small molecules (96.6%) for physicians. Based on patients' and physicians' opinions, the risk of serious infections, malignancies, cardiovascular events, death, relapse, all infections, surgery, and hospitalization should be included in the benefit-risk assessment., Conclusion: Physicians and patients have different priorities in evaluating the benefit-risk balance of a new therapy.

Background and Aim: In view of their frequent onset during childbearing years, the impact of inflammatory bowel diseases [IBD] on reproductive health is of important concern to young women and to the IBD physician. This study aims to assess the fertility and assisted reproductive technologies outcomes in non-surgically treated IBD females., Methods: A systematic review was conducted using MEDLINE, SCOPUS, and EMBASE [until March 2022] to identify studies assessing fertility and assisted reproductive technologies outcomes in women with non-operated IBD, compared with non-IBD patients. Two reviewers independently selected studies, assessed risk of bias, and extracted study data., Results: A total of 14 studies encompassing 18 012 patients with ulcerative colitis [UC] and 14 353 patients with Crohn's disease [CD] were included for analysis. The fertility rate in UC patients and in the general population was comparable, but UC patients tended to have fewer children, mainly by choice. On the contrary, the fertility of CD patients appeared to be reduced. Although a deliberate component cannot be not excluded, the disease itself could affect fertility. Disease activity was associated with reduced fertility in both UC and CD patients. In CD, the colonic involvement of the disease and perianal damage could be associated with subfertility, but data are less consistent. According to the only study reporting the assisted reproductive technologies outcomes, pregnancy rates after in vitro fertilization in subfertile non-operated UC patients and non-IBD patients were similar., Conclusions: There is low-quality evidence from observational studies that patients with CD and relapsing UC may have impaired fertility. After assisted reproductive technologies, pregnancy rates of subfertile non-operated UC patients were similar to those of the general population, although this observation requires further scrutiny in larger studies that should include UC and CD patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aim: Pneumocystis jirovecii pneumonia [PJP] is a very rare, potentially life-threatening pulmonary fungal infection that occurs in immunocompromised individuals including patients with inflammatory bowel disease [IBD]. Our aim was to describe immunosuppressive treatment exposure as well as the outcome in IBD patients with PJP., Methods: PJP cases were retrospectively collected through the COllaborative Network For Exceptionally Rare case reports of the European Crohn's and Colitis Organisation. Clinical data were provided through a case report form., Results: In all, 18 PJP episodes were reported in 17 IBD patients [10 ulcerative colitis and seven Crohn's disease]. The median age at PJP diagnosis was 55 years (interquartile range [IQR], 40-68 years]. Two PJP [11.1%] occurred in patients on triple immunosuppression, 10 patients [55.6%] had double immunosuppressive treatment, four patients [22.2%] had monotherapy and two PJP occurred in absence of immunosuppressive treatment [one in a human immunodeficiency virus patient and one in a patient with a history of autologous stem cell transplantation]. Immunosuppressive therapies included steroids [n = 12], thiopurines [n = 10], infliximab [n = 4], ciclosporin [n = 2], methotrexate [n = 1], and tacrolimus [n = 1]. None of the patients diagnosed with PJP had received prophylaxis. All patients were treated by trimethoprim/sulphamethoxazole or atovaquone and an intensive care unit [ICU] stay was required in seven cases. Two patients [aged 71 and 32 years] died, and one patient had a recurrent episode 16 months after initial treatment. Evolution was favourable for the others., Conclusion: This case series reporting potentially fatal PJP highlights the need for adjusted prophylactic therapy in patients with IBD on immunosuppressive therapy., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Although the therapeutic armamentarium of Inflammatory bowel diseases (IBD) physicians has expanded rapidly in recent years, a proportion of patients remain with a suboptimal response to medical treatment due to primary no response, loss of response or intolerance to currently available drugs. Our growing knowledges of IBD pathophysiology has led to the development of a multitude of new therapies over time, which may, 1 day, be able to address this unmet medical need. This review aims to provide physicians an update of emerging therapies in IBD by focusing on drugs currently in phase 3 clinical trials. Among the most promising molecules are anti-IL-23, JAK-inhibitors, anti-integrins and S1P modulators. While the results in terms of efficacy and safety are fairly clear for some classes, the question of safety remains more uncertain for other classes. Molecules at a more preliminary stage of development (phase 1 and 2), one of which may 1 day offer an optimal benefit-risk ratio, will also be presented as well as their respective mechanisms of action., (© 2022 The Authors. United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that encompass two main phenotypes, namely Crohn's disease and ulcerative colitis. These conditions occur in genetically predisposed individuals in response to environmental factors. Epigenetics, acting by DNA methylation, post-translational histones modifications or by non-coding RNAs, could explain how the exposome (or all environmental influences over the life course, from conception to death) could influence the gene expression to contribute to intestinal inflammation. We performed a scoping search using Medline to identify all the elements of the exposome that may play a role in intestinal inflammation through epigenetic modifications, as well as the underlying mechanisms. The environmental factors epigenetically influencing the occurrence of intestinal inflammation are the maternal lifestyle (mainly diet, the occurrence of infection during pregnancy and smoking); breastfeeding; microbiota; diet (including a low-fiber diet, high-fat diet and deficiency in micronutrients); smoking habits, vitamin D and drugs (e.g., IBD treatments, antibiotics and probiotics). Influenced by both microbiota and diet, short-chain fatty acids are gut microbiota-derived metabolites resulting from the anaerobic fermentation of non-digestible dietary fibers, playing an epigenetically mediated role in the integrity of the epithelial barrier and in the defense against invading microorganisms. Although the impact of some environmental factors has been identified, the exposome-induced epimutations in IBD remain a largely underexplored field. How these environmental exposures induce epigenetic modifications (in terms of duration, frequency and the timing at which they occur) and how other environmental factors associated with IBD modulate epigenetics deserve to be further investigated.

The therapeutic management of older patients with inflammatory bowel disease (IBD) is challenging, particularly because of the absence of evidence-based guidelines for these patients, who seem to frequently be excluded from clinical trials. In this systematic review we investigated the exclusion of older patients with IBD from phase 3 studies registered on PubMed and ClinicalTrials.gov, by assessing the upper limit of age exclusion criteria and the percentage of patients older than 65 years included in the trials. Exclusion criteria other than age were also recorded, and comorbidities were analysed separately. Our review of 222 phase 3 studies shows that older patients are frequently excluded from IBD clinical trials because of their age, which was used as an exclusion criterion in 129 (58%) of the 222 assessed trials. Of the 32 trials that detailed the percentage of included patients who were 65 years or older, only 763 (5·4%) patients of the 14 124 patients included were older than 65 years. In addition to age, patients were also excluded because of comorbidities (mainly renal, hepatic, and cardiovascular, and used as an exclusion criterion in 76% of trials), a history of dysplasia (45% of trials), and previous treatment for IBD (19% of trials). We propose a three-step process that should enable the inclusion of all older patients in IBD clinical trials, regardless of their age, comorbidities, and frailty., Competing Interests: Declaration of interests BC reports lecture fees from AbbVie, Amgen, Ferring Pharmaceuticals, Janssen Pharmaceuticals, and Takeda; and consulting fees from Celltrion and Janssen Pharmaceuticals. VJ has received consulting and advisory board fees from AbbVie, Alimentiv (formerly Robarts Clinical Trials), Arena Pharmaceuticals, Asahi Kasei Pharma, Asieris Pharmaceuticals, Bristol Myers Squibb, Celltrion, Eli Lilly, Ferring Pharmaceuticals, Fresenius Kabi, Galapagos, GlaxoSmithKline, Genentech, Gilead Sciences, Janssen Pharmaceuticals, Merck, Mylan, Pandion, Pendopharm, Pfizer, Protagonist Therapeutics, Reistone Biopharma, Roche, Sandoz, Second Genome, Takeda, Teva Pharmaceuticals, and Topivert Pharma; and speaker's fees from AbbVie, Ferring Pharmaceuticals, Galapagos, Janssen Pharmaceuticals, Pfizer, Shire, and Takeda. SD has served as a consultant for Schering-Plough, AbbVie, Actelion, Alphawasserman, AstraZeneca, Cellerix, Cosmo Pharmaceuticals, Ferring Pharmaceuticals, Genentech, Grünenthal, Johnson & Johnson, Millennium Takeda, Merck Sharp & Dohme, Nikkiso Europe, Novo Nordisk, Nycomed, Pfizer, Pharmacosmos, UCB Pharma, and Vifor; and as a speaker for Pfizer, Takeda, AbbVie, and Janssen Pharmaceuticals. EL reports research grants from Janssen Pharmaceuticals, Pfizer, Ferring Pharmaceuticals, Dr Falk Pharma, AbbVie, and Takeda; educational grants from AbbVie, Janssen Pharmaceuticals, Fresenius Kabi, and Takeda; speaker's fees from AbbVie, Dr Falk Pharma, Ferring Pharmaceuticals, Janssen Pharmaceuticals, Pfizer, Galapagos, and Takeda; advisory board membership of AbbVie, Celgene, Ferring Pharmaceuticals, Janssen Pharmaceuticals, Bristol Myers Squibb, Pfizer, Takeda, Galapagos, Gilead Sciences, Arena Pharmaceuticals, and Eli Lilly; and has served as a consultant for AbbVie. LP-B reports personal fees from Galapagos, AbbVie, Janssen Pharmaceuticals, Genentech, Ferring Pharmaceuticals, Tillots Pharma, Pharmacosmos, Celltrion, Takeda, Boerhinger Ingelheim, Pfizer, Index Pharmaceuticals, Sandoz, Celgene, Biogen, Samsung Bioepis, Alma Bio Therapeutics, Sterna Biologicals, Nestlé, Inotrem, Enterome, Allergan, Merck Sharp & Dohme, Roche, Arena Pharmaceuticals, Gilead Sciences, Hikma Pharmaceuticals, Amgen, Bristol Myers Squibb, Vifor Pharma, Norgine, Mylan, Eli Lilly, Fresenius Kabi, Oppilan Pharma, Sublimity Therapeutics, Applied Molecular Transport, OSE Immunotherapeutics, Enthera, Theravance, and Pandion Therapeutics; grants from AbbVie, Merck Sharp & Dohme, Takeda, and Fresenius Kabi; and stock options for Clinical Trials Mobile Application. SV and AB declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background and Aim: Mesenchymal stem cells [MSCs] have anti-inflammatory and anti-fibrotic properties and could be a potential therapy for Crohn's disease [CD] strictures. In this phase I-II pilot trial, we assessed safety and efficacy of local MSC injection to treat CD strictures., Methods: CD patients with a short [less than 5 cm in length] non-passable stricture accessible by ileocolonoscopy were included. Allogenic bone-marrow derived MSCs were injected in the four quadrants of the stricture. Adverse events and clinical scores were evaluated at each follow-up visit and endoscopy and magnetic resonance enterography were performed at baseline, Week [W]12 and W48. The main judgement criterion for efficacy was the complete [defined by the ability to pass the ileocolonoscope] or partial [defined by a diameter increase] resolution of the stricture at W12. Second efficacy criteria included assessment of the stricture at W48 and evolution of clinical scores at W12 and W48., Results: We performed 11 MSC injections in 10 CD patients [three primary and seven anastomotic strictures; one stricture injected twice]. MSC injections were well tolerated but four hospitalisations for occlusion were reported. At W12, five patients presented a complete or partial resolution of the stricture [two complete and three partial]. Seven patients were re-evaluated at W48 [one dilated, one operated, and one lost to follow-up] and four patients had a complete resolution. The evolution of clinical scores between W0, W12, and W48 was not statistically significant., Conclusions: MSCs injection in CD stricture was well tolerated and may offer a benefit., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: The small-bowel capsule endoscopy (VCE) has been validated in the investigation of obscure gastrointestinal bleeding (OGIB). The aim of this study was to evaluate the clinical impact of VCE for OGIB in routine practice, in terms of subsequent management and the risk of rebleeding., Methods: Our retrospective study analyzed the VCE at the CHU of Liège from March 2016 to December 2019 (cohort of 110 patients with OGIB)., Results: We found a diagnostic yield of 58 %, a change in therapeutic attitude in 39 % of patients and a recurrence rate of 22.5 % (out of 102 patients followed at 2 years). The rate of rebleeding was particularly low in patients with normal VCE and in those for whom a therapeutic modification was made. Finally, about 45 % of patients did not have any change in therapeutic attitude nor recurrence., Conclusion: VCE leads to a therapeutic modification in about 40 % of patients with a low risk of relapse. However, VCE could be avoided in some patients as evidenced by a subgroup representing 45 % of patients for whom there was no therapeutic modification nor recurrence.

Background and Aims: Intestinal fibrosis is a common complication of Crohn's disease [CD]. It is characterised by an accumulation of fibroblasts differentiating into myofibroblasts secreting excessive extracellular matrix. The potential role of the intestinal epithelium in this fibrotic process remains poorly defined., Methods: We performed a pilot proteomic study comparing the proteome of surface epithelium, isolated by laser-capture microdissection, in normal and fibrotic zones of resected ileal CD strictures [13 zones collected in five patients]. Proteins of interests were validated by immunohistochemistry [IHC] in ileal and colonic samples of stricturing CD [n = 44], pure inflammatory CD [n = 29], and control [n = 40] subjects. The pro-fibrotic role of one selected epithelial protein was investigated through in-vitro experiments using HT-29 epithelial cells and a CCD-18Co fibroblast to myofibroblast differentiation model., Results: Proteomic study revealed an endoplasmic reticulum [ER] stress proteins increase in the epithelium of CD ileal fibrotic strictures, including anterior gradient protein 2 homologue [AGR2] and binding-immunoglobulin protein [BiP]. This was confirmed by IHC. In HT-29 cells, tunicamycin-induced ER stress triggered AGR2 intracellular expression and its secretion. Supernatant of these HT-29 cells, pre-conditioned by tunicamycin, led to a myofibroblastic differentiation when applied on CCD-18Co fibroblasts. By using recombinant protein and blocking agent for AGR2, we demonstrated that the secretion of this protein by epithelial cells can play a role in the myofibroblastic differentiation., Conclusions: The development of CD fibrotic strictures could involve epithelial ER stress and particularly the secretion of AGR2., (© The Author(s) 2021. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Ileal and colonic Crohn's disease seem to be two separate entities., Aims: To describe the main physiological distinctions between the small and the large intestine and to analyse the differences between ileal and colonic Crohn's disease., Methods: The relevant literature was critically examined and synthesised., Results: The small and large intestine have fundamental distinctions (anatomy, cellular populations, immune defence, microbiota). The differences between ileal and colonic Crohn's disease are highlighted by a heterogeneous body of evidence including clinical features (natural history of the disease, efficacy of treatments, and monitoring), epidemiological data (smoking status, age, gender) and biological data (genetics, microbiota, immunity, mesenteric fat). However, the contribution of these factors to disease location remains poorly understood., Conclusion: The classification of ileal and colonic Crohn's disease as distinct subphenotypes is well supported by the literature. Understanding of these differences could be exploited to develop more individualised patient care., (© 2021 John Wiley & Sons Ltd.)

Condyloma acuminatum (CA) is a manifestation of Human Papillomavirus (HPV) infection which usually occurs in genital and perianal regions. We report a 46-year-old man with an ulcerative proctitis diagnosed four years earlier, asymptomatic for a long time under azathioprine but without any follow-up for three years. A colonoscopy was performed prior to potential immunosuppressive treatment discontinuation and showed a circumferential "laterally spreading tumour" in the rectum. Surprisingly biopsies revealed a CA with a very focally high-grade intra-epithelial lesion. Azathioprine was stopped and a transanal surgical resection was performed. At guided anamnesis, patient confirmed to be a former active "men who have sex with men". No recurrence of proctitis occurred despite azathioprine discontinuation. A retrospective review of the histological sections suggests that it was, in fact, an intestinal spirochetosis misdiagnosed as inflammatory bowel disease. Involvement of the rectal mucosa by HPV is a rare condition and this may have been promoted by inappropriate immunosuppressive treatment., Competing Interests: The authors declare that they have no conflict of interest, (© Acta Gastro-Enterologica Belgica.)

We report the case of a 24-year-old female patient with spontaneous rupture of a splenic artery aneurysm in the third trimester of pregnancy. Pregnancy, throughout the physiological and hormonal changes it imposes, promotes the occurrence of aneurysm of the splenic artery and its rupture. Although this is a rare complication, its prognosis is severe and its typical clinical picture associating abdominal pain, hypotension and anemia is misleading for the clinician who likelier evokes a retroplacental hematoma or an uterine rupture. The maternal and foetal survival depends on rapid diagnosis and multidisciplinary management. Thus, it's important for the clinician to consider this differential diagnosis when abdominal pain or hemoperitoneum occurs in pregnant woman, particularly during the third trimester of pregnancy.

Background: The pivotal clinical trials have largely demonstrated the efficacy and safety of ustekinumab in Crohn's disease. Real-life cohorts published so far only include very few bio-naïve patients. This study assesses effectiveness and safety of ustekinumab in bio-naïve and bio-failure patients treated with ustekinumab in routine practice and look for predictors of response., Methods: We performed a retrospective monocentric study. Initial response was assessed by maintenance therapy beyond week 16. Sustained response was assessed by the continuation or cessation of therapy over time for another reason than stopping in sustained remission. Treatment persistence was assessed by Kaplan Meier curves and predictors of treatment persistence were studied by univariate and multivariate Cox model., Results: Out of 156 recorded patients, three patients were still in their induction phase at time of analysis and 5 patients were lost to follow-up, leaving 148 patients for clinical effectiveness analyses, including 35 bio-naïve when starting ustekinumab. A maintenance therapy was initiated in 79.7%. At one year, the probability to be still treated with ustekinumab was 73.8%. Treatment cessation increased with smoking in multivariate analysis. Previous biologic failure (as a whole), CRP and fecal calprotectin baseline levels did not influence initial response and treatment persistence., Conclusion: A large proportion of CD patients initially respond to ustekinumab and continue this treatment beyond one year. Treatment persistence is as high in bio-failure as in bio-naïve patients., Competing Interests: Declaration of Competing Interest E Louis has received fees for: Research Grant: Takeda, Pfizer; Educational Grant: Abbvie, Takeda, Janssen; Speaker Fees: Abbvie, Ferring, MSD, Falk, Takeda, Hospira, Janssen, Pfizer, Celgene; Advisory Board: Abbvie, Ferring, MSD, Takeda, Celgene, Hospira, Janssen; Consultant: Abbvie., (Copyright © 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Ulcerative colitis (UC) patients have a greater risk of developing colorectal cancer through inflammation-dysplasia-carcinoma sequence of transformation. The histopathological diagnosis of dysplasia is therefore of critical clinical relevance, but dysplasia may be difficult to distinguish from inflammatory changes., Methods: A proteomic pilot study on 5 UC colorectal dysplastic patients highlighted proteins differentially distributed between paired dysplastic, inflammatory and normal tissues. The best candidate marker was selected and immunohistochemistry confirmation was performed on AOM/DSS mouse model lesions, 37 UC dysplasia, 14 UC cancers, 23 longstanding UC, 35 sporadic conventional adenomas, 57 sporadic serrated lesions and 82 sporadic colorectal cancers., Results: Differential proteomics found 11 proteins significantly more abundant in dysplasia compared to inflammation, including Solute carrier family 12 member 2 (SLC12A2) which was confidently identified with 8 specific peptides and was below the limit of quantitation in both inflammatory and normal colon. SLC12A2 immunohistochemical analysis confirmed the discrimination of preneoplastic and neoplastic lesions from inflammatory lesions in mice, UC and in sporadic contexts. A specific SLC12A2 staining pattern termed "loss of gradient" reached 89% sensitivity, 95% specificity and 92% accuracy for UC-dysplasia diagnosis together with an inter-observer agreement of 95.24% (multirater κfree of 0.90; IC95%: 0.78 - 1.00). Such discrimination could not be obtained by Ki67 staining. This specific pattern was also associated with sporadic colorectal adenomas and cancers., Conclusions: We found a specific SLC12A2 immunohistochemical staining pattern in precancerous and cancerous colonic UC-lesions which could be helpful for diagnosing dysplasia and cancer in UC and non-UC patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: To compare dynamic contrast-enhanced (DCE)-MRI parameters in affected and unaffected segments of CD patients with those of a control group, and to assess the correlation between DCE-MRI parameters and clinical index of activity (HBI) as well as biomarkers (CRP and faecal calprotectin)., Methods: We performed a single-center prospective study of CD patients and control subjects who underwent DCE-MRI. Regions of interest were drawn in segments and the program (Olea Medical - Canon) provided values for transfer constant (Ktrans), fractional volume of extravascular-extracellular space (Ve), slope of enhancement (SoE), time to maximum enhancement (TME), maximum enhancement (ME) and enhancement ratio (ER) which were determined and compared., Results: Fifteen CD patients (mean age 42 years; 10 women) and 7 healthy subjects (mean age 40.4 years; 6 women) were included. Paired comparisons of affected and unaffected segments in CD showed a significant increase of all parameters in affected segments, except for ER and TME. When comparing to controls, the affected segments did not show any significant difference, while a significant decrease in most of the parameters (except for ER and TME) was observed when comparing unaffected segments of CD patients to controls. In CD, significant correlations between DCE-MRI parameters and biomarkers (CRP, faecal calprotectin) were more frequent in unaffected segments than in affected segments., Conclusions: Significant differences in perfusion parameters were observed between affected and unaffected segments of CD patients and between unaffected segments and those of control subjects. This suggests complex perfusion changes in both unaffected and affected intestinal segments in CD.