Results of the Seventh Scientific Workshop of ECCO: Precision Medicine in IBD – Challenges and Future Directions 

Robin J Dart, Pierre Ellul, Michael Scharl, Christopher A Lamb Scientific Workshop Steering Committee

doi : 10.1093/ecco-jcc/jjab049

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1407–1409

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Results of the Seventh Scientific Workshop of ECCO: Precision Medicine in IBD—What, Why, and How 

Claudio Fiocchi, Gabriele Dragoni, Dimitrios Iliopoulos, Konstantinos Katsanos, Vicent Hernandez Ramirez, Kohei Suzuki, Scientific Workshop Steering Committee

doi : 10.1093/ecco-jcc/jjab051

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1410–1430

Many diseases that affect modern humans fall in the category of complex diseases, thus called because they result from a combination of multiple aetiological and pathogenic factors. Regardless of the organ or system affected, complex diseases present major challenges in diagnosis, classification, and management. Current forms of therapy are usually applied in an indiscriminate fashion based on clinical information, but even the most advanced drugs only benefit a limited number of patients and to a variable and unpredictable degree. This ‘one measure does not fit all’ situation has spurred the notion that therapy for complex disease should be tailored to individual patients or groups of patients, giving rise to the notion of ‘precision medicine’ [PM].

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Results of the Seventh Scientific Workshop of ECCO: Precision Medicine in IBD—Disease Outcome and Response to Therapy 

Bram Verstockt, Nurulamin M Noor, Urko M Marigorta, Polychronis Pavlidis, Parakkal Deepak, Ryan C Ungaro, Scientific Workshop Steering Committee

doi : 10.1093/ecco-jcc/jjab050

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1431–1442

Inflammatory bowel diseases [IBD] are a heterogeneous spectrum with two extreme phenotypes, Crohn’s disease [CD] and ulcerative colitis [UC], which both represent numerous phenotypical variations. Hence, we should no longer approach all IBD patients similarly, but rather aim to rethink clinical classifications and modify treatment algorithms to usher in a new era of precision medicine in IBD. This scientific ECCO workshop aims to provide a state-of-the-art overview on prognostic and predictive markers, shed light on key questions in biomarker development, propose best practices in IBD biomarker development [including trial design], and discuss the potential for multi-omic data integration to help drive further advances to make precision medicine a reality in IBD.

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Results of the Seventh Scientific Workshop of ECCO: Precision Medicine in IBD—Prediction and Prevention of Inflammatory Bowel Disease 

Joana Torres, Jonas Halfvarson, Iago Rodríguez-Lago, Charlotte R H Hedin, Tine Jess, Marla Dubinsky, Kenneth Croitoru, Jean-Frédéric Colombel Scientific Workshop Steering Committee

doi : 10.1093/ecco-jcc/jjab048

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1443–1454

Inflammatory bowel disease [IBD] is a complex chronic disorder with no clear aetiology and no known cure. Despite recent advances in overall disease management and improved therapeutics, patients with IBD still experience a substantial burden. Furthermore, as the incidence continues to increase in developing areas of the world, it is expected that the burden of IBD to society will increase and exert tremendous pressure on health care systems worldwide. Therefore, new strategies to prevent the global increase of IBD are urgently required. Data are being progressively acquired on the period preceding disease diagnosis, which support the concept that IBD has a preclinical period that may reveal the triggers of disease and may be amenable to early intervention. Having a better knowledge of this preclinical period will increase the potential not only for improved understanding of disease pathogenesis and improved therapeutics, but also for disease prediction and prevention.

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Prevalence and Progression of Incidental Terminal Ileitis on Non-diagnostic Colonoscopy: A Systematic Review and Meta-analysis

Manasi Agrawal, Mario Bento- Miranda, Samantha Walsh, Neeraj Narula, Jean-Frederic Colombel, Ryan C Ungaro

doi : 10.1093/ecco-jcc/jjab030

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1455–1463

Incidentally diagnosed terminal ileitis [IDTI] has been reported among asymptomatic persons undergoing non-diagnostic colonoscopy. The purpose of our study was to determine the prevalence and long-term outcomes of asymptomatic terminal ileitis.

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Increased Risk of High-grade Cervical Neoplasia in Women with Inflammatory Bowel Disease: A Case-controlled Cohort Study 

R L Goetgebuer, J E Kreijne, C A Aitken, G Dijkstra, F Hoentjen, N K de Boer, B Oldenburg, A E van der Meulen, C I J Ponsioen, M J Pierik, F J van Kemenade, I M C M de Kok, A G Siebers, J Manniën, C J van der Woude, A C de Vries on behalf of the Dutch Initiative on Crohn and Colitis [ICC]

doi : 10.1093/ecco-jcc/jjab036

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1464–1473

Women with inflammatory bowel disease [IBD] may be at higher risk for cervical intraepithelial neoplasia [CIN]. However, data are conflicting. The aim of this study was to assess the risk of high-grade dysplasia and cancer [CIN2+] in IBD women and identify risk factors.

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Bariatric Surgery and Risk of New-onset Inflammatory Bowel Disease: A Nationwide Cohort Study

Kristine H Allin, Rikke K Jacobsen, Ryan C Ungaro, Jean-Frederic Colombel, Alexander Egeberg, Marie Villumsen, Tine Jess

doi : 10.1093/ecco-jcc/jjab037

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1474–1480

The aim of this study was to examine the risk of new-onset inflammatory bowel disease [IBD] following bariatric surgery.

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Validated Indices for Histopathologic Activity Predict Development of Colorectal Neoplasia in Ulcerative Colitis

Rish K Pai, Douglas J Hartman, Jonathan A Leighton, Shabana F Pasha, Claudia Ramos Rivers, Miguel Regueiro, David G Binion, Reetesh K Pai

doi : 10.1093/ecco-jcc/jjab042

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1481–1490

To correlate histologic activity in surveillance colonoscopies with the development of colorectal neoplasia in ulcerative colitis [UC].

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Expression of MAdCAM-1 and Gut-homing T Cells in Inflamed Pouch Mucosa

Manon de Krijger, Manon E Wildenberg, Aart Mookhoek, Sascha Verheul, Wouter J de Jonge, Cyriel Y Ponsioen

doi : 10.1093/ecco-jcc/jjab041

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1491–1499

Pouchitis is a common complication following formation of an ileal pouch-anal anastomosis [IPAA] after proctocolectomy for ulcerative colitis [UC]. Gut-specific lymphocyte trafficking mechanisms have been identified as players in the pathogenesis of UC. In the present study, we aimed to characterise the presence of lymphocyte subsets expressing gut-homing molecules in pouches and peripheral blood of UC patients with and without pouchitis.

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Diving into Inflammation: A Pilot Study Exploring the Dynamics of the Immune–Microbiota Axis in Ileal Tissue Layers of Patients with Crohn’s Disease

Edda Russo, Francesco Giudici, Federica Ricci, Stefano Scaringi, Giulia Nannini, Ferdinando Ficari, Cristina Luceri, Elena Niccolai, Simone Baldi, Mario D’Ambrosio, Matteo Ramazzotti, Amedeo Amedei

doi : 10.1093/ecco-jcc/jjab034

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1500–1516

The pathogenesis of Crohn’s disease [CD] is still unclear. Disorders in the mucosal immunoregulation and its crosstalk with the microbiota may represent an important component in tissue injury. We aimed to characterize the molecular immune response distribution within the ileal layers and to evaluate the correlated microbiota in pathological/healthy settings comparing first surgery/relapse clinical conditions.

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Therapeutic Potential of a Self-Assembling Peptide Hydrogel to Treat Colonic Injuries Associated with Inflammatory Bowel Disease 

Toshihiro Araki, Keiichi Mitsuyama, Hiroshi Yamasaki, Masaru Morita, Kozo Tsuruta, Atsushi Mori, Tetsuhiro Yoshimura, Shuhei Fukunaga, Kotaro Kuwaki, Shinichiro Yoshioka, Hidetoshi Takedatsu, Tatsuyuki Kakuma, Jun Akiba, Takuji Torimura

doi : 10.1093/ecco-jcc/jjab033

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1517–1527

The Self-assembling Peptide Hydrogel [SAPH, PuraMatrix], a fully synthetic peptide solution designed to replace collagen, has recently been used to promote mucosal regeneration in iatrogenic ulcers following endoscopic submucosal dissection. Herein, we evaluated its utility in ulcer repair using a rat model of topical trinitrobenzene sulphonic acid [TNBS]-induced colonic injuries.

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Colitis Linked to Endoplasmic Reticulum Stress Induces Trypsin Activity Affecting Epithelial Functions

Núria Solà Tapias, Alexandre Denadai-Souza, Claire Rolland-Fourcade, Muriel Quaranta-Nicaise, Catherine Blanpied, Marlène Marcellin, Anissa Edir, Corinne Rolland, Carla Cirillo, Gilles Dietrich, Laurent Alric, Guillaume Portier, Sylvain Kirzin, Delphine Bonnet, Emmanuel Mas, Odile Burlet-Schiltz, Céline Deraison, Chrystelle Bonnart, Nathalie Vergnolle, Frédérick Barreau

doi : 10.1093/ecco-jcc/jjab035

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1528–1541

Intestinal epithelial cells [IECs] from inflammatory bowel disease [IBD] patients exhibit an excessive induction of endoplasmic reticulum stress [ER stress] linked to altered intestinal barrier function and inflammation. Colonic tissues and the luminal content of IBD patients are also characterized by increased serine protease activity. The possible link between ER stress and serine protease activity in colitis-associated epithelial dysfunctions is unknown. We aimed to study the association between ER stress and serine protease activity in enterocytes and its impact on intestinal functions

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MALAT1 Maintains the Intestinal Mucosal Homeostasis in Crohn’s Disease via the miR-146b-5p-CLDN11/NUMB Pathway

Ying Li, Liguo Zhu, Peng Chen, Ying Wang, Guang Yang, Gaoshi Zhou, Li Li, Rui Feng, Yun Qiu, Jing Han, Baili Chen, Yao He, Zhirong Zeng, Minhu Chen, Shenghong Zhang

doi : 10.1093/ecco-jcc/jjab040

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1542–1557

Intestinal homeostasis disorder is critical for developing Crohn’s disease [CD]. Maintaining mucosal barrier integrity is essential for intestinal homeostasis, preventing intestinal injury and complications. Among the remarkably altered long non-coding RNAs [lncRNAs] in CD, we aimed to investigate whether metastasis-associated lung adenocarcinoma transcript 1 [MALAT1] modulated CD and consequent disruption of intestinal homeostasis.

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Schlafen 11 Is a Novel Target for Mucosal Regeneration in Ulcerative Colitis

Sho Watanabe, Ryu Nishimura, Tomoaki Shirasaki, Nobuhiro Katsukura, Shuji Hibiya, Susumu Kirimura, Mariko Negi, Ryuichi Okamoto, Yuka Matsumoto, Tetsuya Nakamura, Mamoru Watanabe, Kiichiro Tsuchiya

doi : 10.1093/ecco-jcc/jjab032

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1558–1572

Ulcerative colitis [UC] is a chronic inflammatory disease of the colon with an intractable course. Although the goal of UC therapy is to achieve mucosal healing, the pathogenesis of mucosal injury caused by chronic inflammation remains unknown. We therefore aim to elucidate molecular mechanisms of mucosal injury by establishing in vitro and in vivo humanised UC-mimicking models.

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The Burden of Inflammatory Bowel Disease in Europe in 2020

Mirabella Zhao, Lóránt Gönczi, Peter L Lakatos, Johan Burisch

doi : 10.1093/ecco-jcc/jjab029

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1573–1587

New data suggest that incidence and prevalence of inflammatory bowel diseases [IBD] are still increasing worldwide, and approximately 0.2% of the European population suffer from IBD at the present time. Medical therapy and disease management have evolved significantly in recent decades, with an emphasis on tight objective monitoring of disease progression and a treat-to-target approach in Europe and also worldwide, aiming to prevent early bowel damage and disability. Surgery rate declined over time in Europe, with 10–30% of CD and 5–10% of UC patients requiring a surgery within 5 years. The health economic burden associated with IBD is high in Europe. Direct health care costs [approximately €3500 in CD and €2000 in UC per patient per year] have shifted from hospitalisation and surgery towards drug-related expenditures with the increasing use of biologic therapy and other novel agents, and substantial indirect costs arise from work productivity loss [approximately €1900 per patient yearly]. The aim of this paper is to provide an updated review of the burden of IBD in Europe by discussing current data on epidemiology, disease course, risk for surgery, hospitalisation, and mortality and cancer risks, as well as the economic aspects, patient disability, and work impairment, by discussing the latest population-based studies from the region.

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Restored Macrophage Function Ameliorates Disease Pathophysiology in a Mouse Model for IL10 Receptor-deficient Very Early Onset Inflammatory Bowel Disease

Mania Ackermann, Adele Mucci, Amanda McCabe, Sandy Frei, Kayla Wright, Scott B Snapper, Nico Lachmann, David A Williams, Christian Brendel

doi : 10.1093/ecco-jcc/jjab031

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1588–1595

Mutations in IL10 or the IL10 receptor lead to very early onset [VEO] inflammatory bowel disease [IBD], a life-threatening disease which is often unresponsive to conventional medication. Recent studies have demonstrated that defective IL-10 receptor signalling in innate immune cells is a key driver of severe intestinal inflammation in VEO-IBD. Specifically, IL10 unresponsiveness of macrophages, which govern the tight balance between pro- and anti-inflammatory responses in the intestinal system, plays a central role in the events leading to excessive inflammatory responses and the development of IBD.

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Fucosylation and Sialylation of Fc-Fragment of anti-Tumour Necrosis Factor Alpha Antibodies do not Influence Their Immunogenicity in Monocyte-Derived Dendritic Cells

Marcin Wawrzyniak, Yasser Morsy, Radoslav Mladenov, Giulia Tontodonati, Yagmur Turgay, Stefan Herwig, Jonathan Back, Manuela Mally, Amirreza Faridmoayer, Michael Scharl

doi : 10.1093/ecco-jcc/jjab038

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Pages 1596–1601

Background and Aims: Antibodies targeting tumor necrosis factor-alpha [TNF-alpha] are a mainstay in the treatment of inflammatory bowel disease. However, they fail to demonstrate efficacy in a considerable proportion of patients. On the other hand, glycosylation of antibodies might influence not only their immunogenicity but also their structure and function. We investigated whether specific glycosylation patterns of the Fc-fragment would affect the immunogenicity of anti-TNF-alpha antibody in monocyte-derived dendritic cells.

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Corrigendum to: Abstracts of the 15th Congress of ECCO Vienna, Austria, February 12–15, 2020 

doi : 10.1093/ecco-jcc/jjaa246

Journal of Crohn's and Colitis, Volume 15, Issue 9, September 2021, Page 1602

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