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1. Controversies in the management of anti-TNF therapy in patients with Crohn’s disease: a Delphi consensus

Author: Ignacio Marin-Jimenez, Guillermo Bastida, Daniel Carpio, Fernando Muñoz, Yago González-Lama, Elena Ricart, Daniel Ceballos, Daniel Ginard, and Luis Menchen
Subjects: Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Background Despite research, there are still controversial areas in the management of Crohn’s disease (CD).Objective To establish practical recommendations on using anti-tumour necrosis factor (TNF) drugs in patients with moderate-to-severe CD.Methods Clinical controversies in the management of CD using anti-TNF therapies were identified. A comprehensive literature review was performed, and a national survey was launched to examine current clinical practices when using anti-TNF therapies. Their results were discussed by expert gastroenterologists within a nominal group meeting, and a set of statements was proposed and tested in a Delphi process.Results Qualitative study. The survey and Delphi process were sent to 244 CD-treating physicians (response rate: 58%). A total of 14 statements were generated. All but two achieved agreement. These statements cover: (1) use of first-line non-anti-TNF biological therapy; (2) role of HLA-DQA1*05 in daily practice; (3) attitudes in primary non-response and loss of response to anti-TNF therapy due to immunogenicity; (4) use of ustekinumab or vedolizumab if a change in action mechanism is warranted; (5) anti-TNF drug level monitoring; (6) combined therapy with an immunomodulator.Conclusion This document sought to pull together the best evidence, experts’ opinions, and treating physicians’ attitudes when using anti-TNF therapies in patients with CD.
Published: 2024
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2. Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committeeResearch in context

Author: Raffaella Greco, Tobias Alexander, Nicoletta Del Papa, Fabian Müller, Riccardo Saccardi, Fermin Sanchez-Guijo, Georg Schett, Basil Sharrack, John A. Snowden, Karin Tarte, Francesco Onida, Isabel Sánchez-Ortega, Joachim Burman, Cristina Castilla Llorente, Ricard Cervera, Fabio Ciceri, Andrea Doria, Jörg Henes, James Lindsay, Andreas Mackensen, Paolo A. Muraro, Elena Ricart, Montserrat Rovira, Tsila Zuckerman, Ibrahim Yakoub-Agha, and Dominique Farge
Subjects: Autoimmune diseases, Mesenchymal stem cells, Regulatory T cells, Chimeric antigen receptor (CAR) T cells, Medicine (General), R5-920
Abstract: Summary: Autoimmune diseases (ADs) are characterized by loss of immune tolerance, high chronicity, with substantial morbidity and mortality, despite conventional immunosuppression (IS) or targeted disease modifying therapies (DMTs), which usually require repeated administration. Recently, novel cellular therapies (CT), including mesenchymal stromal cells (MSC), Chimeric Antigen Receptors T cells (CART) and regulatory T cells (Tregs), have been successfully adopted in ADs. An international expert panel of the European Society for Blood and Marrow Transplantation and the International Society for the Cell and Gene Therapy, reviewed all available evidence, based on the current literature and expert practices, on use of MSC, CART and Tregs, in AD patients with rheumatological, neurological, and gastroenterological indications. Expert-based consensus and recommendations for best practice and quality of patient care were developed to support clinicians, scientists, and their multidisciplinary teams, as well as patients and care providers and will be regularly updated.
Published: 2024
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3. Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease

Author: Alba Garrido-Trigo, Ana M. Corraliza, Marisol Veny, Isabella Dotti, Elisa Melón-Ardanaz, Aina Rill, Helena L. Crowell, Ángel Corbí, Victoria Gudiño, Miriam Esteller, Iris Álvarez-Teubel, Daniel Aguilar, M. Carme Masamunt, Emily Killingbeck, Youngmi Kim, Michael Leon, Sudha Visvanathan, Domenica Marchese, Ginevra Caratù, Albert Martin-Cardona, Maria Esteve, Ingrid Ordás, Julian Panés, Elena Ricart, Elisabetta Mereu, Holger Heyn, and Azucena Salas
Subjects: Science
Abstract: Abstract Ulcerative colitis and Crohn’s disease are chronic inflammatory intestinal diseases with perplexing heterogeneity in disease manifestation and response to treatment. While the molecular basis for this heterogeneity remains uncharacterized, single-cell technologies allow us to explore the transcriptional states within tissues at an unprecedented resolution which could further understanding of these complex diseases. Here, we apply single-cell RNA-sequencing to human inflamed intestine and show that the largest differences among patients are present within the myeloid compartment including macrophages and neutrophils. Using spatial transcriptomics in human tissue at single-cell resolution (CosMx Spatial Molecular Imaging) we spatially localize each of the macrophage and neutrophil subsets identified by single-cell RNA-sequencing and unravel further macrophage diversity based on their tissue localization. Finally, single-cell RNA-sequencing combined with single-cell spatial analysis reveals a strong communication network involving macrophages and inflammatory fibroblasts. Our data sheds light on the cellular complexity of these diseases and points towards the myeloid and stromal compartments as important cellular subsets for understanding patient-to-patient heterogeneity.
Published: 2023
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4. Trends in Targeted Therapy Usage in Inflammatory Bowel Disease: TRENDY Study of ENEIDA

Author: Celia Gómez-Labrador, Elena Ricart, Marisa Iborra, Eva Iglesias, María Dolores Martín-Arranz, Luisa de Castro, Ruth De Francisco, Francisco Javier García-Alonso, Ana Sanahuja, Carla J. Gargallo-Puyuelo, Francisco Mesonero, María José Casanova, Míriam Mañosa, Montserrat Rivero, Marta Calvo, Mónica Sierra-Ausin, Carlos González-Muñoza, Xavier Calvet, Santiago García-López, Jordi Guardiola, Lara Arias García, Lucía Márquez-Mosquera, Ana Gutiérrez, Yamile Zabana, Mercè Navarro-Llavat, Rufo Lorente Poyatos, Marta Piqueras, Leyanira Torrealba, Fernando Bermejo, Ángel Ponferrada-Díaz, José L. Pérez-Calle, Manuel Barreiro-de Acosta, Coral Tejido, José Luis Cabriada, Ignacio Marín-Jiménez, Óscar Roncero, Yolanda Ber, Luis Fernández-Salazar, Blau Camps Aler, Alfredo J. Lucendo, Jordina Llaó, Luis Bujanda, Carmen Muñoz Villafranca, Eugeni Domènech, María Chaparro, and Javier P. Gisbert
Subjects: biologics, biosimilars, targeted therapy, inflammatory bowel disease, Crohn’s disease, ulcerative colitis, Pharmacy and materia medica, RS1-441
Abstract: Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn’s disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment.
Published: 2024
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5. Author Correction: Macrophage and neutrophil heterogeneity at single-cell spatial resolution in human inflammatory bowel disease

Author: Alba Garrido-Trigo, Ana M. Corraliza, Marisol Veny, Isabella Dotti, Elisa Melón-Ardanaz, Aina Rill, Helena L. Crowell, Ángel Corbí, Victoria Gudiño, Miriam Esteller, Iris Álvarez-Teubel, Daniel Aguilar, M. Carme Masamunt, Emily Killingbeck, Youngmi Kim, Michael Leon, Sudha Visvanathan, Domenica Marchese, Ginevra Caratù, Albert Martin-Cardona, Maria Esteve, Ingrid Ordás, Julian Panés, Elena Ricart, Elisabetta Mereu, Holger Heyn, and Azucena Salas
Subjects: Science
Published: 2024
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6. Autologous hematopoietic stem cell transplantation for refractory Crohn's disease

Author: Antonio Giordano and Elena Ricart
Subjects: Transplant. Crohn. Refractory. Hematopoietic., Dermatology, RL1-803, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Despite recent advances in Crohn’s disease (CD) therapy, with ever-new treatments available, there is still a relevant percentage of patients with refractory disease who do not achieve adequate clinical response and are not amenable to intestinal surgery. A joint consensus of the European societies for blood and marrow transplantation and inflammatory bowel disease has recognized the therapeutic role of autologous hematopoietic stem cell (HSCs) transplantation in this cluster of patients. The therapy produces a reset of patients’ immune system and the subsequent recovery of more self-tolerant inflammatory cells. In several case series and prospective clinical trials, this treatment was demonstrated to be able to induce clinical remission and heal mucosal damage, although providing only a temporary improvement. The use of deep immunosuppression as part of transplanting protocols represents the major limitation of this technique as causes a high adverse event rate, including mortality of up to 2%. Many new protocols have been assessed and are under investigation with the intent to reduce complications. The present review summarizes evidence of the efficacy and safety of autologous HSCs transplantation in refractory CD.
Published: 2022
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7. Experimental and genetic evidence for the impact of CD5 and CD6 expression and variation in inflammatory bowel disease

Author: Sergi Casadó-Llombart, María Velasco-de Andrés, Cristina Català, Alejandra Leyton-Pereira, Rebeca Gutiérrez-Cózar, Belén Suárez, Noelia Armiger, Esther Carreras, Miriam Esteller, Elena Ricart, Ingrid Ordás, Javier P. Gisbert, María Chaparro, María Esteve, Lucía Márquez, David Busquets, Eva Iglesias, Esther García-Planella, María Dolores Martín-Arranz, Juliane Lohmann, C. Korcan Ayata, Jan Hendrik Niess, Pablo Engel, Julián Panés, Azucena Salas, Eugeni Domènech, Francisco Lozano, ENEIDA Project of GETECCU, Alfredo J. Lucendo, Jordi Guardiola, Xavier Calvet, Lorenzo Olivá́n, and Marta Piqueras
Subjects: Crohn’s disease, inflammatory bowel disease, ulcerative colitis, CD5, CD6, Immunologic diseases. Allergy, RC581-607
Abstract: Crohn’s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) resulting from the interaction of multiple environmental, genetic and immunological factors. CD5 and CD6 are paralogs encoding lymphocyte co-receptors involved in fine-tuning intracellular signals delivered upon antigen-specific recognition, microbial pattern recognition and cell adhesion. While CD5 and CD6 expression and variation is known to influence some immune-mediated inflammatory disorders, their role in IBD remains unclear. To this end, Cd5- and Cd6-deficient mice were subjected to dextran sulfate sodium (DSS)-induced colitis, the most widely used experimental animal model of IBD. The two mouse lines showed opposite results regarding body weight loss and disease activity index (DAI) changes following DSS-induced colitis, thus supporting Cd5 and Cd6 expression involvement in the pathophysiology of this experimental IBD model. Furthermore, DNA samples from IBD patients of the ENEIDA registry were used to test association of CD5 (rs2241002 and rs2229177) and CD6 (rs17824933, rs11230563, and rs12360861) single nucleotide polymorphisms with susceptibility and clinical parameters of CD (n=1352) and UC (n=1013). Generalized linear regression analyses showed association of CD5 variation with CD ileal location (rs2241002CC) and requirement of biological therapies (rs2241002C-rs2229177T haplotype), and with poor UC prognosis (rs2241002T-rs2229177T haplotype). Regarding CD6, association was observed with CD ileal location (rs17824933G) and poor prognosis (rs12360861G), and with left-sided or extensive UC, and absence of ankylosing spondylitis in IBD (rs17824933G). The present experimental and genetic evidence support a role for CD5 and CD6 expression and variation in IBD’s clinical manifestations and therapeutic requirements, providing insight into its pathophysiology and broadening the relevance of both immunomodulatory receptors in immune-mediated disorders.
Published: 2022
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8. Immigrant IBD Patients in Spain Are Younger, Have More Extraintestinal Manifestations and Use More Biologics Than Native Patients

Author: Ana Gutiérrez, Pedro Zapater, Elena Ricart, María González-Vivó, Jordi Gordillo, David Olivares, Isabel Vera, Míriam Mañosa, Javier P. Gisbert, Mariam Aguas, Eugenia Sánchez-Rodríguez, Maia Bosca-Watts, Viviana Laredo, Blau Camps, Ignacio Marín-Jiménez, Yamile Zabana, María Dolores Martín-Arranz, Roser Muñoz, Mercè Navarro, Eva Sierra, Lucía Madero, Milagros Vela, José Lázaro Pérez-Calle, Empar Sainz, Xavier Calvet, Lara Arias, Victor Morales, Fernando Bermejo, Luis Fernández-Salazar, Manuel Van Domselaar, Luisa De Castro, Cristina Rodríguez, Carmen Muñoz-Villafranca, Rufo Lorente, Montserrat Rivero, Eva Iglesias, Belén Herreros, David Busquets, Joan Riera, María Pilar Martínez-Montiel, Marta Roldón, Oscar Roncero, Esther Hinojosa, Mónica Sierra, Jesús Barrio, Ruth De Francisco, José Huguet, Olga Merino, Daniel Carpio, Daniel Ginard, Fernando Muñoz, Marta Piqueras, Pedro Almela, Federico Argüelles-Arias, Guillermo Alcaín, Luis Bujanda, Noemí Manceñido, Alfredo J. Lucendo, Pilar Varela, Iago Rodríguez-Lago, Laura Ramos, Laura Sempere, Eva Sesé, Manuel Barreiro-de Acosta, Eugeni Domènech, and Rubén Francés
Subjects: immigrant, phenotype, biologics, inflammatory bowel disease, Crohn's disease, ulcerative colitis, Medicine (General), R5-920
Abstract: BackgroundPrevious studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain.MethodsProspective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients.ResultsWe included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p < 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p < 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p < 0.001) than native patients. Family history of IBD (9 vs. 14%, p < 0.001) and smoking (30 vs. 40%, p < 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p < 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p < 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92–2.58, p < 0.001)] and using biologics [OR: 1.13 (1.0–1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses.ConclusionsCompared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe.
Published: 2022
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9. The Genetic Diversity and Dysfunctionality of Catalase Associated with a Worse Outcome in Crohn’s Disease

Author: Marisa Iborra, Inés Moret, Enrique Busó, José Luis García-Giménez, Elena Ricart, Javier P. Gisbert, Eduard Cabré, Maria Esteve, Lucía Márquez-Mosquera, Esther García-Planella, Jordi Guardiola, Federico V. Pallardó, Carolina Serena, Francisco Algaba-Chueca, Eugeni Domenech, Pilar Nos, and Belén Beltrán
Subjects: catalase, inflammatory bowel disease, Crohn’s disease, oxidative stress, antioxidant genes, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract: Chronic gut inflammation in Crohn’s disease (CD) is associated with an increase in oxidative stress and an imbalance of antioxidant enzymes. We have previously shown that catalase (CAT) activity is permanently inhibited by CD. The purpose of the study was to determine whether there is any relationship between the single nucleotide polymorphisms (SNPs) in the CAT enzyme and the potential risk of CD associated with high levels of oxidative stress. Additionally, we used protein and regulation analyses to determine what causes long-term CAT inhibition in peripheral white mononuclear cells (PWMCs) in both active and inactive CD. We first used a retrospective cohort of 598 patients with CD and 625 age-matched healthy controls (ENEIDA registry) for the genotype analysis. A second human cohort was used to study the functional and regulatory mechanisms of CAT in CD. We isolated PWMCs from CD patients at the onset of the disease (naïve CD patients). In the genotype-association SNP analysis, the CAT SNPs rs1001179, rs475043, and rs525938 showed a significant association with CD (p < 0.001). Smoking CD patients with the CAT SNP rs475043 A/G genotype had significantly more often penetrating disease (p = 0.009). The gene expression and protein levels of CAT were permanently reduced in the active and inactive CD patients. The inhibition of CAT activity in the PWMCs of the CD patients was related to a low concentration of CAT protein caused by the downregulation of CAT-gene transcription. Our study suggests an association between CAT SNPs and the risk of CD that may explain permanent CAT inhibition in CD patients together with low CAT gene and protein expression.
Published: 2022
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10. Fecal Calprotectin for Small Bowel Crohn’s Disease: Is It a Cutoff Issue?

Author: Cristina Romero-Mascarell, Gloria Fernández-Esparrach, Cristina Rodríguez-De Miguel, Maria Carme Masamunt, Sonia Rodríguez, Jordi Rimola, Miguel Urpí, Gherzon Simon Casanova, Ingrid Ordás, Elena Ricart, Berta Caballol, Agnès Fernández-Clotet, Julià Panés, Josep Llach, and Begoña González-Suárez
Subjects: Crohn’s disease, inflammatory bowel disease, small bowel capsule endoscopy, magnetic resonance enterography, fecal calprotectin, Medicine (General), R5-920
Abstract: (1) Background: Fecal calprotectin (FC) correlates well with colonic inflammatory activity of Crohn’s disease (CD); data about relation of FC and small bowel (SB) lesions are still contradictory. The main aim was to analyze the relationship between FC levels and SB inflammatory activity in patients with established or suspected Crohn’s disease, assessed by small bowel capsule endoscopy (SBCE) or magnetic resonance enterography (MRE). (2) Methods: Two cohorts of patients were included: 1. Prospective data were collected from patients with established or suspected CD who underwent SBCE and FC (Cohort A); 2. A retrospective cohort of patients who underwent MRE and FC determination (Cohort B). Different cutoffs for FC were tested in both cohorts. (3) Results: 83 patients were included and 66 were finally analyzed. A total of 69.6% had SB lesions seen by SBCE (n = 25) or MRE (n = 21). FC mean levels were 605.74 + 607.07 μg/g (IQ range: 99.00–878.75), being significantly higher in patients with SB lesions compared to patients without lesions (735.91 + 639.70 μg/g (IQ range: 107.75–1366.25) vs. 306.35 + 395.26 μg/g (IQ range: 78.25–411.0), p < 0.005). For cohort A, 25 out of 35 patients had SB lesions and a significant correlation between Lewis Score and FC levels was achieved (R2: 0.34; p = 0.04). FC sensitivity (S), specificity (E), positive predictive value (PPV), and negative predictive values (NPV) for predicting SB lesions were 80%, 50%, 80%, and 50%, respectively, for FC > 100 µg/g. For cohort B, inflammatory SB activity, measured by MaRIA score, was detected in 21 out of 31 patients (67.7%). Patients with positive findings in MRE had significantly higher values of FC than those with no lesions (944.9 + 672.1 µg/g vs. 221 + 212.2 µg/g, p < 0.05). S, E, PPV, and NPV of FC were 89%, 50%, 77.2%, and 71.4% for FC levels > 100 µg/g. The higher sensitivity and specificity of the FC levels for the detection of SB lesions with SBCE and MRE was obtained for an FC cutoff >265 μg/g and >430 μg/g, respectively. (4) Conclusions: FC has a good correlation with the presence of SB lesions, assessed by SBCE and MRE, in patients with established or suspected Crohn’s disease. However, the ideal cutoff is here proven to be higher than previously reported. Multicenter and large prospective studies are needed in order to establish definitive FC cutoff levels.
Published: 2022
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11. A Novel Strategy to Study the Invasive Capability of Adherent-Invasive Escherichia coli by Using Human Primary Organoid-Derived Epithelial Monolayers

Author: Aida Mayorgas, Isabella Dotti, Marta Martínez-Picola, Miriam Esteller, Queralt Bonet-Rossinyol, Elena Ricart, Azucena Salas, and Margarita Martínez-Medina
Subjects: organoid-derived epithelial monolayers (ODM), adherent-invasive E. coli (AIEC), bacterial infection, intestinal epithelial cells (IECs), inflammatory bowel disease (IBD), Immunologic diseases. Allergy, RC581-607
Abstract: Over the last decades, Adherent-Invasive Escherichia coli (AIEC) has been linked to the pathogenesis of Crohn’s Disease. AIEC’s characteristics, as well as its interaction with the gut immune system and its role in intestinal epithelial barrier dysfunction, have been extensively studied. Nevertheless, the currently available techniques to investigate the cross-talk between this pathogen and intestinal epithelial cells (IECs) are based on the infection of immortalized cell lines. Despite their many advantages, cell lines cannot reproduce the conditions in tissues, nor do they reflect interindividual variability or gut location-specific traits. In that sense, the use of human primary cultures, either healthy or diseased, offers a system that can overcome all of these limitations. Here, we developed a new infection model by using freshly isolated human IECs. For the first time, we generated and infected monolayer cultures derived from human colonic organoids to study the mechanisms and effects of AIEC adherence and invasion on primary human epithelial cells. To establish the optimal conditions for AIEC invasion studies in human primary organoid-derived epithelial monolayers, we designed an infection-kinetics study to assess the infection dynamics at different time points, as well as with two multiplicities of infection (MOI). Overall, this method provides a model for the study of host response to AIEC infections, as well as for the understanding of the molecular mechanisms involved in adhesion, invasion and intracellular replication. Therefore, it represents a promising tool for elucidating the cross-talk between AIEC and the intestinal epithelium in healthy and diseased tissues.
Published: 2021
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12. Multi-omic modelling of inflammatory bowel disease with regularized canonical correlation analysis.

Author: Lluís Revilla, Aida Mayorgas, Ana M Corraliza, Maria C Masamunt, Amira Metwaly, Dirk Haller, Eva Tristán, Anna Carrasco, Maria Esteve, Julian Panés, Elena Ricart, Juan J Lozano, and Azucena Salas
Subjects: Medicine, Science
Abstract: BackgroundPersonalized medicine requires finding relationships between variables that influence a patient's phenotype and predicting an outcome. Sparse generalized canonical correlation analysis identifies relationships between different groups of variables. This method requires establishing a model of the expected interaction between those variables. Describing these interactions is challenging when the relationship is unknown or when there is no pre-established hypothesis. Thus, our aim was to develop a method to find the relationships between microbiome and host transcriptome data and the relevant clinical variables in a complex disease, such as Crohn's disease.ResultsWe present here a method to identify interactions based on canonical correlation analysis. We show that the model is the most important factor to identify relationships between blocks using a dataset of Crohn's disease patients with longitudinal sampling. First the analysis was tested in two previously published datasets: a glioma and a Crohn's disease and ulcerative colitis dataset where we describe how to select the optimum parameters. Using such parameters, we analyzed our Crohn's disease data set. We selected the model with the highest inner average variance explained to identify relationships between transcriptome, gut microbiome and clinically relevant variables. Adding the clinically relevant variables improved the average variance explained by the model compared to multiple co-inertia analysis.ConclusionsThe methodology described herein provides a general framework for identifying interactions between sets of omic data and clinically relevant variables. Following this method, we found genes and microorganisms that were related to each other independently of the model, while others were specific to the model used. Thus, model selection proved crucial to finding the existing relationships in multi-omics datasets.
Published: 2021
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13. An RORγt Oral Inhibitor Modulates IL-17 Responses in Peripheral Blood and Intestinal Mucosa of Crohn's Disease Patients

Author: Helena Bassolas-Molina, Ernest Raymond, Mark Labadia, Joseph Wahle, Elena Ferrer-Picón, Mark Panzenbeck, Jie Zheng, Christian Harcken, Robert Hughes, Michael Turner, Dustin Smith, Elisabeth Calderón-Gómez, Míriam Esteller, Anna Carrasco, Maria Esteve, Isabella Dotti, Ana Maria Corraliza, Maria Carme Masamunt, Clàudia Arajol, Jordi Guardiola, Elena Ricart, Gerald Nabozny, and Azucena Salas
Subjects: Th17, commensal antigens, T-cell-transfer, RORγt inhibition, Crohn's disease, Immunologic diseases. Allergy, RC581-607
Abstract: Background and Aims: Despite the negative results of blocking IL-17 in Crohn's disease (CD) patients, selective modulation of Th17-dependent responses warrants further study. Inhibition of retinoic acid-related orphan receptor gamma (RORγt), the master regulator of the Th17 signature, is currently being explored in inflammatory diseases. Our aim was to determine the effect of a novel oral RORγt antagonist (BI119) in human CD and on an experimental model of intestinal inflammation.Methods: 51 CD patients and 11 healthy subjects were included. The effects of BI119 were tested on microbial-stimulated peripheral blood mononuclear cells (PBMCs), intestinal crypts and biopsies from CD patients. The ability of BI119 to prevent colitis in vivo was assessed in the CD4+CD45RBhigh T cell transfer model.Results: In bacterial antigen-stimulated PBMCs from CD patients, BI119 inhibits Th17-related genes and proteins, while upregulating Treg and preserving Th1 and Th2 signatures. Intestinal crypts cultured with supernatants from BI119-treated commensal-specific CD4+ T cells showed decreased expression of CXCL1, CXCL8 and CCL20. BI119 significantly reduced IL17 and IL26 transcription in colonic and ileal CD biopsies and did not affect IL22. BI119 has a more profound effect in ileal CD with additional significant downregulation of IL23R, CSF2, CXCL1, CXCL8, and S100A8, and upregulation of DEFA5. BI119 significantly prevented development of clinical, macroscopic and molecular markers of colitis in the T-cell transfer model.Conclusions: BI119 modulated CD-relevant Th17 signatures, including downregulation of IL23R while preserving mucosa-associated IL-22 responses, and abrogated experimental colitis. Our results provide support to the use of RORγt antagonists as a novel therapy to CD treatment.
Published: 2018
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14. Immunological Changes in Blood of Newborns Exposed to Anti-TNF-α during Pregnancy

Author: Ana Esteve-Solé, Àngela Deyà-Martínez, Irene Teixidó, Elena Ricart, Macarena Gompertz, Maria Torradeflot, Noemí de Moner, Europa Azucena Gonzalez, Ana Maria Plaza-Martin, Jordi Yagüe, Manel Juan, and Laia Alsina
Subjects: adalimumab, inflammatory bowel disease, infliximab, monoclonal antibodies, pregnancy, prenatal exposure, Immunologic diseases. Allergy, RC581-607
Abstract: BackgroundAlthough anti-TNF-α monoclonal antibodies are considered safe during pregnancy, there are no studies on the development of the exposed-infant immune system. The objective was to study for the first time the impact of throughout pregnancy exposure to anti-TNF-α has an impact in the development of the infant’s immune system, especially B cells and the IL-12/IFN-γ pathway.MethodsProspective study of infants born to mothers with inflammatory bowel disease treated throughout pregnancy with anti-TNF-α (adalimumab/infliximab). Infants were monitored both clinically and immunologically at birth and at 3, 6, 12, and 18 months.ResultsWe included seven patients and eight healthy controls. Exposed infants had detectable levels of anti-TNF-α until 6 months of age; they presented a more immature B- and helper T-phenotype that normalized within 12 months, with normal immunoglobulin production and vaccine responses. A decreased Treg cell frequency at birth that inversely correlated with mother’s peripartum anti-TNF-α levels was observed. Also, a decreased response after mycobacterial challenge was noted. Clinically, no serious infections occurred during follow-up. Four of seven had atopia.ConclusionThis study reveals changes in the immune system of infants exposed during pregnancy to anti-TNF-α. We hypothesize that a Treg decrease might facilitate hypersensitivity and that defects in IL-12/IFN-γ pathway might place the infant at risk of intracellular infections. Pediatricians should be aware of these changes. Although new studies are needed to confirm these results, our findings are especially relevant in view of a likely increase in the use of these drugs during pregnancy in the coming years.
Published: 2017
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15. Pancreatitis-associated protein does not predict disease relapse in inflammatory bowel disease patients.

Author: Tiago Nunes, Maria Josefina Etchevers, Maria Jose Sandi, Susana Pinó Donnay, Teddy Grandjean, Maria Pellisé, Julián Panés, Elena Ricart, Juan Lucio Iovanna, Jean-Charles Dagorn, Mathias Chamaillard, and Miquel Sans
Subjects: Medicine, Science
Abstract: BackgroundThe pancreatitis-associated protein (PAP) is increased in the serum of active inflammatory bowel disease (IBD) patients and its levels seem to be correlated with disease activity. Our aim was to evaluate the usefulness of serum and fecal PAP measurements to predict relapse in patients with inactive IBD.Materials and methodsWe undertook a 12-month prospective study that included 66 Crohn's disease (CD) and 74 ulcerative colitis (UC) patients. At inclusion, patients were in clinical remission, defined by a Harvey-Bradshaw (HB) Index≤4 (CD) or a partial Mayo Score (MS)ResultsActive CD patients had an increased mean serum PAP at the diagnosis of the flare (104.1 ng/ml) and 3 months prior to activity (22.68 ng/ml) compared with patients in remission (13.26 ng/ml), pConclusionSerum PAP is increased only in active CD patients, but this marker does not predict disease activity. Inactive UC patients have marked low levels of PAP in fecal samples compared with CD patients.
Published: 2014
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16. Gram-negative enterobacteria induce tolerogenic maturation in dexamethasone conditioned dendritic cells.

Author: Raquel Cabezón, Elena Ricart, Carolina España, Julián Panés, and Daniel Benitez-Ribas
Subjects: Medicine, Science
Abstract: Dendritic cells have been investigated in clinical trials, predominantly with the aim of stimulating immune responses against tumours or infectious diseases. Thus far, however, no clinical studies have taken advantage of their specific immunosuppressive potential. Tolerogenic DCs may represent a new therapeutic strategy for human immune-based diseases, such as Crohn's disease, where the perturbations of the finely tuned balance between the immune system and the microflora result in disease. In the present report, we describe the generation of tolerogenic DCs from healthy donors and Crohn's disease patients using clinical-grade reagents in combination with dexamethasone as immunosuppressive agent and characterize their response to maturation stimuli. Interestingly, we found out that dexamethasone-conditioned DCs keep their tolerogenic properties to Gram-negative bacteria. Other findings included in this study demonstrate that the combination of dexamethasone with a specific cytokine cocktail yielded clinical-grade DCs with the following characteristics: a semi-mature phenotype, a pronounced shift towards anti-inflammatory versus inflammatory cytokine production and low T-cell stimulatory properties. Importantly, in regard to their clinical application, the tolerogenic phenotype of DCs remained stable after the elimination of dexamethasone and after a second stimulation with LPS or bacteria. All these properties make this cell product suitable to be tested in clinical trials of inflammatory conditions including Crohn's disease.
Published: 2012
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17. Neutrophilic dermatoses in a patient with collagenous colitis

Author: Didac Barco, Maria A. Barnadas, Esther Roé, Francisco J. Sancho, Elena Ricart, and Agustín Alomar
Subjects: Neutrophilic dermatoses, Sweet's syndrome, neutrophilic panniculitis, inflammatory bowel disease, collagenous colitis, Dermatology, RL1-803
Abstract: We report the case of a 75-year old woman with collagenous colitis who presented with erythematous and edematous plaques on the periorbital and eyelid regions, accompanied by oral ulcers. Histopathology showed a dermal neutrophilic infiltrate plus mild septal and lobular panniculitis with lymphocytes, neutrophils and eosinophils. Five years earlier she had presented a flare of papules and vesicles on the trunk, together with oral ulcers; a skin biopsy revealed a neutrophilic dermal infiltrate and Sweet’s syndrome was diagnosed. Both the neutrophilic panniculitis and the Sweet’s syndrome were accompanied by fever, malaise and diarrhea. Cutaneous and intestinal symptoms disappeared with corticoid therapy. The two types of neutrophilic dermatoses that appeared in periods of colitis activity suggest that intestinal and cutaneous manifestations may be related.
Published: 2010
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18. Serrated polyposis syndrome associated with long-standing inflammatory bowel disease

Author: Jesús Castro, Miriam Cuatrecasas, Francesc Balaguer, Elena Ricart, and María Pellisé
Subjects: Serrated polyposis syndrome, Ulcerative colitis, Crohn's disease, Inflammatory bowel disease, Colonoscopy, Colorectal cancer, Chromoendoscopy, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract: Inflammatory bowel disease (IBD) patients are at an increased risk of developing colorectal cancer (CRC), which is thought to develop via the adenoma-carcinoma pathway. Since the discovery of the serrated carcinogenesis pathway and serrated polyposis syndrome (SPS), the incidence of carcinomas arising from serrated lesions in IBD patients has increased. We report three cases of long-standing IBD patients with associated serrated polyposis syndrome. At present, the pathophysiology of serrated lesions in IBD patients is not fully understood and there is a lack of strong evidence to confirm whether the manifestation of both conditions represents an increased risk of developing cancer. Therefore, more accurate surveillance guidelines are needed and are being actively investigated at present.
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19. Recommendations of the Spanish Group on Crohn’s Disease and Ulcerative Colitis on the importance, screening and vaccination in inflammatory bowel disease patients

Author: Rocío Ferreiro-Iglesias, Marta Piqueras, Elena Ricart, Laura Sempere, Mariona Roca, Javier Martín de Carpi, Olga Benítez, Yamile Zabana, Míriam Mañosa, Francisco Rodríguez-Moranta, and Manuel Barreiro-de Acosta
Subjects: General Medicine
Published: 2022

20. Predictors of bowel damage in the long-term progression of Crohn’s disease

Author: Agnes Fernández-Clotet, Julian Panés, Elena Ricart, Jesús Castro-Poceiro, Maria Carme Masamunt, Sonia Rodríguez, Berta Caballol, Ingrid Ordás, and Jordi Rimola
Subjects: General Medicine
Abstract: Crohn's disease (CD) is a chronic inflammatory bowel disorder that progresses to bowel damage (BD) over time. An image-based index, the Lémann index (LI), has been developed to measure cumulative BD.To characterize the long-term progression of BD in CD based on changes in the LI and to determine risk factors for long-term progression.This was a single-center longitudinal cohort study. Patients who had participated in prospective studies on the accuracy of magnetic resonance imaging using endoscopy as a gold standard and who had a follow-up of at least 5 years were re-evaluated after 5-12 years.Seventy-two patients were included. LI increased in 38 patients (52.8%), remained unchanged in 9 patients (12.5%), and decreased in 25 patients (34.7%). The small bowel score and surgery subscale significantly increased (BD, as assessed by the LI, progressed in half of the patients with CD over a period of 5-12 years. The main determinants of BD progression were ileal location, stricturing/fistulizing phenotype, and disease duration.
Published: 2022

21. Motorized Spiral Enteroscopy Is Effective in Patients with Prior Abdominal Surgery

Author: Antonio Giordano, Gherzon Casanova, Miriam Escapa, Gloria Fernández-Esparrach, Àngels Ginès, Oriol Sendino, Isis K. Araujo, Andrés Cárdenas, Henry Córdova, Julia Martínez-Ocon, Graciela Martínez-Palli, Francesc Balaguer, Josep Llach, Elena Ricart, and Begoña González-Suárez
Subjects: Physiology, Gastroenterology
Abstract: Motorized Spiral Enteroscopy (MSE) reduces procedure time and increases insertion depth into the small bowel; however, there is scarce evidence on factors affecting MSE efficacy.To evaluate diagnostic yield and adverse events of MSE including patients with prior major abdominal surgery.A prospective observational study was conducted on patients undergoing MSE from June 2019 to December 2021. Demographic characteristics, procedure time, depth of maximum insertion (DMI), technical success, diagnostic yield, and adverse events were collected.Seventy-four anterograde (54.4%) and 62 retrograde (45.6%) enteroscopies were performed in 117 patients (64 males, median age 67 years). Fifty patients (42.7%) had prior major abdominal surgery. Technical success was 91.9% for anterograde and 90.3% for retrograde route. Diagnostic yield was 71.6% and 61.3%, respectively. The median DMI was 415 cm (264-585) for anterograde and 120 cm (37-225) for retrograde enteroscopy. In patients with prior major abdominal surgery, MSE showed significantly longer small bowel insertion time (38 vs 29 min, p = 0.004), with similar diagnostic yield (61 vs 71.4%, p = 0.201) and DMI (315 vs 204 cm, p = 0.226). The overall adverse event rate was 10.3% (SAE 1.5%), with no differences related to prior abdominal surgery (p = 0.598). Patients with prior surgeries directly involving the gastrointestinal tract showed lower DMI (189 vs 374 cm, p = 0.019) with equal exploration time (37.5 vs 38 min, p = 0.642) compared to those with other abdominal surgeries.MSE is effective and safe in patients with major abdominal surgery, although longer procedure times were observed. A lower depth of insertion was detected in patients with gastrointestinal surgery.
Published: 2022

22. Autologous hematopoietic stem cell transplantation for refractory Crohn's disease

Author: Antonio Giordano and Elena Ricart
Published: 2023

23. Medical consultation in ulcerative colitis: Key elements for improvement

Author: Yago González-Lama, Elena Ricart, Ana Cábez, Pilar Fortes, Susana Gómez, Francesc Casellas, Institut Català de la Salut, [González-Lama Y] Inflammatory Bowel Disease Unit, Department of Gastroenterology and Hepatology, Hospital Universitario Puerta de Hierro-Majadahonda, Madrid, Spain. [Ricart E] Inflammatory Bowel Disease Unit, Department of Gastroenterology, Hospital Clínic, Barcelona, Spain. Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain. [Cábez A] Department of Medical, Pfizer Spain, Madrid, Spain. [Fortes P] Department of Medical, Pfizer Spain, Madrid, Spain. [Gómez S] Servicio de Reumatología, Hospital Universitario de Salamanca, Salamanca, Spain. [Casellas F] Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBERehd), Barcelona, Spain. Servei de l’Aparell Digestiu, Vall d'Hebron Institut de Recerca (VHIR), Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
Subjects: Colitis ulcerosa - Tractament, enfermedades del sistema digestivo::enfermedades gastrointestinales::gastroenteritis::colitis::colitis ulcerosa [ENFERMEDADES], Diagnosis::Clinical Decision-Making [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Gastroenterology, diagnóstico::toma de decisiones clínicas [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Presa de decisions, General Medicine, Other subheadings::/therapy [Other subheadings], Digestive System Diseases::Gastrointestinal Diseases::Gastroenteritis::Colitis::Colitis, Ulcerative [DISEASES], Otros calificadores::/terapia [Otros calificadores]
Abstract: Medical consultation; Shared decision making; Ulcerative colitis Consulta médica; Toma de decisiones compartida; Colitis ulcerosa Consulta mèdica; Presa de decisions compartida; Colitis ulcerosa Ulcerative colitis (UC) is a chronic inflammatory disease with a high impact. In order to improve patient outcomes, the clinician-patient relationship in daily practice is critical. Clinical guidelines provide a framework for UC diagnosis and treatment. However, standard procedures and the medical content focused upon medical consultations in UC patients has not yet been defined. Moreover, UC is a complex disease, given that patient characteristics and patient needs have been proven to vary during clinical consultation since establishing the diagnosis and upon the course of the disease. In this article, we have discussed the key elements and specific objectives to consider in medical consultation, such as diagnosis, first visits, follow-up visits, active disease patients, patients on topical therapies, new treatment initiation, refractory patients, extra-intestinal manifestations, as well as challenging situations. The key elements have been mentioned to comprise effective communication techniques, motivational interviewing (MI), as well as information and educational aspects, or organizational issues. The key elements to be implemented in daily practice were reported to comprise several general principles like duly prepared consultations, in addition to honesty and empathy with patients, as well as effective communication techniques, MI, information and educational points, or organizational issues. The role of other healthcare professionals such as specialized nurses, psychologists, or the use of checklists was also discussed and commented on.
Published: 2023

24. Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU

Author: Manuel Barreiro-de, Acosta, Agnès, Fernández-Clotet, Francisco, Mesonero, Francisco Javier, García-Alonso, María José, Casanova, Margarita, Fernández-de la Varga, Fiorella, Cañete, Luisa, de Castro, Ana, Gutiérrez, Beatriz, Sicilia, Victoria, Cano, Olga, Merino, Ruth, de Francisco, Irene, González-Partida, Gerard, Surís, Leyanira, Torrealba, Rocío, Ferreiro-Iglesias, Beatriz, Castro, Lucía, Márquez, Ana, Sobrino, Ainara, Elorza, Xavier, Calvet, Pilar, Varela, Raquel, Vicente, Luis, Bujanda, Laura, Lario, Noemí, Manceñido, Mariana F, García-Sepulcre, Eva, Iglesias, Cristina, Rodríguez, Marta, Piqueras, Juan Ángel, Ferrer Rosique, Alfredo J, Lucendo, Olga, Benítez, Melody, García, David, Olivares, Carlos, González-Muñoza, Beatriz, López-Cauce, Victor Jair, Morales Alvarado, Katerina, Spicakova, Alicia, Brotons, Fernando, Bermejo, Pedro, Almela, Nahia, Ispízua, Pau, Gilabert, Carlos, Tardillo, Fernando, Muñoz, Pablo, Navarro, Rosa Eva, Madrigal Domínguez, Pau, Sendra, Esther, Hinojosa, Empar, Sáinz, María Dolores, Martín-Arranz, Daniel, Carpio, Elena, Ricart, Berta, Caballol, Laura, Núñez, Jesús, Barrio, Javier P, Gisbert, Marisa, Iborra, Margalida, Calafat, Vicent, Hernández, Roser Muñoz, Pérez, José Luis, Cabriada, Eugeni, Domènech, and Iago, Rodríguez-Lago
Subjects: Hepatology, Gastroenterology
Abstract: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease.Adult patients with CD-related fistulae who received at least one biologic agent for this condition from the prospectively-maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic or periostomal fistulae. The primary endpoint was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses.A total of 760 patients from 53 hospitals (673 receiving anti-TNFs, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (IQR, 26-102), 240 patients required surgery, with surgery rates of 32%, 41%, 24% among those under anti-TNF, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, while non-smokers, and combination therapy with an immunomodulator reduced this risk.Biologic therapy is beneficial in approximately three quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one third still undergo surgery due to refractory disease. Some patient and lesion-related factors can identify patients who will obtain more benefit from these drugs.
Published: 2023

25. Macrophage and neutrophil heterogeneity at single-cell spatial resolution in inflammatory bowel disease

Author: Alba Garrido-Trigo, Ana M. Corraliza, Marisol Veny, Isabella Dotti, Elisa Melon-Ardanaz, Aina Rill, Helena L. Crowell, Ángel Corbí, Victoria Gudiño, Miriam Esteller, Iris Álvarez-Teubel, Daniel Aguilar, M Carme Masamunt, Emily Killingbeck, Youngmi Kim, Michael Leon, Sudha Visvanathan, Domenica Marchese, Ginevra Caratù, Albert Martin-Cardona, Maria Esteve, Julian Panés, Elena Ricart, Elisabetta Mereu, Holger Heyn, and Azucena Salas
Abstract: Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic inflammatory intestinal diseases that show a perplexing heterogeneity in manifestations and response to treatment. The molecular basis for this heterogeneity remains uncharacterized. We applied single-cell RNA sequencing and CosMx™ Spatial Molecular Imaging to human colon and found the highest diversity in cellular composition in the myeloid compartment of UC and CD patients. Besides resident macrophage subsets (M0 and M2), patients showed a variety of activated macrophages including classical (M1 CXCL5 and M1 ACOD1) and new inflammation-dependent alternative (IDA) macrophages. In addition, we captured intestinal neutrophils in three transcriptional states. Subepithelial IDA macrophages expressedNRG1, which promotes epithelial differentiation. In contrast,NRG1lowIDA macrophages were expanded within the submucosa and in granulomas, in proximity to abundant inflammatory fibroblasts, which we suggest may promote macrophage activation. We conclude that macrophages sense and respond to unique tissue microenvironments, potentially contributing to patient-to-patient heterogeneity.
Published: 2022

26. 43 - LOS HALLAZGOS DE LA ENTERO-RM A LA SEMANA 46 DESPUÉS DE INICIAR UN TRATAMIENTO BIOLÓGICO PREDICEN LA EVOLUCIÓN A LARGO PLAZO EN PACIENTES CON ENFERMEDAD DE CROHN

Author: Agnès Fernández-Clotet, Ingrid Ordás, Berta Caballol, Maria Carme Masamunt, Sonia Rodríguez, Julian Panés, Elena Ricart, and Jordi Rimola
Subjects: Hepatology, Gastroenterology
Published: 2023

27. 34 - POSICIONAMIENTO DE LAS TERAPIAS DIRIGIDAS EN LA ENFERMEDAD INFLAMATORIA INTESTINAL (EII) EN VIDA REAL: ESTUDIO TRENDY DEL REGISTRO ENEIDA

Author: Celia Gómez-Labrador, Elena Ricart, Marisa Iborra, Eva Iglesias, M. Dolores Martín-Arranz, Luisa de Castro, Ruth de Francisco, Francisco Javier García-Alonso, Ana Sanahuja Martínez, Carla J. Gargallo-Puyuelo, Francisco Mesonero, María José Casanova, Miriam Mañosa, Montserrat Rivero, Marta Calvo, Mónica Sierra-Ausin, Carlos González-Muñoza, Xavier Calvet, Santiago García-López, Jordi Guardiola, Lara Arias García, Lucía Márquez-Mosquera, Ana Gutiérrez, Yamile Zabana, Merce Navarro, Rufo Lorente Poyatos, Marta Piqueras, Leyanira Torrealba, Fernando Bermejo, Ángel Ponferrada Díaz, José L Pérez-Calle, Manuel Barreiro-de Acosta, Coral Tejido, José Luis Cabriada, Ignacio Marín-Jiménez, Óscar Roncero, Yolanda Ber, Luis Fernández-Salazar, Blau Camps Aler, Alfredo J Lucendo Villarín, Jordina Llaó, Luis Bujanda, Carmen Muñoz Villafranca, Eugeni Domènech, María Chaparro, and Javier P. Gisbert
Subjects: Hepatology, Gastroenterology
Published: 2023

28. 79 - EFICACIA, SEGURIDAD Y ACEPTABILIDAD DEL CAMBIO DE INFLIXIMAB ENDOVENOSO A SUBCUTÁNEO EN PRÁCTICA CLÍNICA DE ENFERMEDAD INFLAMATORIA INTESTINAL

Author: Berta Caballol, Agnès Fernández-Clotet, Julià Panés, Maria Carme Masamunt, Marta Gallego, Rebeca Barastegui, Alejandro Vara, Àngel Giner, Elena Ricart, and Ingrid Ordàs
Subjects: Hepatology, Gastroenterology
Published: 2023

29. 98 - CONSULTA MÉDICA PARA PACIENTES CON COLITIS ULCEROSA: ELEMENTOS CLAVE PARA MEJORARLA

Author: Yago González-Lama, Elena Ricart, Ana Cabez, Pilar Fortes, Susana Gómez, and Francesc Casellas
Subjects: Hepatology, Gastroenterology
Published: 2023

30. 41 - BENEFICIO DE LOS PROGRAMAS DE TRANSICIÓN EN ENFERMEDAD INFLAMATORIA INTESTINAL: ESTUDIO BUTTERFLY DE GETECCU Y SEGHNP

Author: Cristina Rubín de Célix, Javier Martín-de-Carpi, Gemma Pujol-Muncunill, Laura María Palomino, Marta Velasco Rodríguez-Belvís, Rafael Martín-Masot, Víctor Manuel Navas-López, Elena Ricart, María José Casanova, Alejandro Rodríguez Martínez, Eduardo Leo-Carnerero, Alba Alcaraz, Miriam Mañosa, Vicent Hernández, María Consuelo Cobelas Cobelas, César Sánchez, Luis Menchén, Francisco Mesonero, Manuel Barreiro-De Acosta, Nazareth Martínon, Coral Tejido Sandoval, Alicia Rendo Vázquez, Pilar Corsino, Raquel Vicente, Alejandro Hernández-Camba, José Ramón Alberto Alonso, I. Alonso-Abreu, Ana María Castro Millán, Laia Peries Reverter, Beatriz Castro, Estela Fernández-Salgado, M Mercedes Busto Cuiñas, José Manuel Benítez, Lucía Madero, Fernando Clemente, Sabino Riestra, Santiago Jiménez- Treviño, Maia Boscá-Watts, Elena Crehuá-Gaudiza, Marta Calvo Moya, José María Huguet, Ester-María Largo-Blanco, Leticia González Vives, Rocío Plaza, Iván Guerra, Josefa Barrio, Laura Escartín, Erika Alfambra, Noelia Cruz, M Carmen Muñoz, María Guadalupe Muñoz Pino, Manuel Van Domselaar, Belén Botella, David Monfort Miquel, M Carmen Rodríguez Grau, Agustín De La Mano, Yolanda Ber, María Calvo Iñiguez, Teresa de Jesús Martínez-Pérez, María Chaparro, and Javier P. Gisbert
Subjects: Hepatology, Gastroenterology
Published: 2023

31. Validation of the Simplified Magnetic Resonance Index of Activity [sMARIA] Without Gadolinium-enhanced Sequences for Crohn’s Disease

Author: Victor Sapena, Nunzia Capozzi, Sonia Rodríguez, Ingrid Ordás, Jordi Rimola, Ignacio Alfaro, Julián Panés, Jesús Castro-Poceiro, Maria Carme Masamunt, Elena Ricart, and Agnès Fernández-Clotet
Subjects: Adult, Male, medicine.medical_specialty, Gadolinium, chemistry.chemical_element, Disease, Severity of Illness Index, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Internal medicine, Outcome Assessment, Health Care, Humans, Medicine, Derivation, Inflammation, Biological Products, Crohn's disease, medicine.diagnostic_test, business.industry, Patient Acuity, Area under the curve, Magnetic resonance imaging, Colonoscopy, General Medicine, Gold standard (test), medicine.disease, Magnetic Resonance Imaging, Endoscopy, Immunity, Active, chemistry, 030220 oncology & carcinogenesis, Female, Tumor Necrosis Factor Inhibitors, 030211 gastroenterology & hepatology, Immunotherapy, business
Abstract: Background Gadolinium-enhanced sequences are not included in the simplified Magnetic Resonance Index of Activity [sMARIA], but in the derivation of this index readers had access to these sequences. The current study aimed to validate the sMARIA without gadolinium-enhanced sequences for assessing disease activity, severity, and response to treatment in patients with Crohn’s disease. Methods We prospectively included patients with active Crohn’s disease and at least one segment with severe inflammation [ulcers] at ileocolonoscopy, who required treatment with biologic drugs. Patients were evaluated by both magnetic resonance enterography [MRE] and ileocolonoscopy at baseline and 46 weeks after initiation of medical treatment. We compared the quantification of disease activity and response to treatment with sMARIA versus with ileocolonoscopy Crohn’s Disease Index of Severity [CDEIS], considered the gold standard. Results Data from both MRE and ileocolonoscopy 46 weeks after treatment initiation were available for 39 of the 50 patients. As in the derivation study, the optimal cutoffs were sMARIA ≥1 for predicting active disease (area under the curve [AUC] 0.92) and sMARIA ≥2 for predicting the presence of ulcers at ileocolonoscopy [AUC 0.93]. In evaluating the response to treatment, the sMARIA detected endoscopic ulcer healing at the segment level [sMARIA Conclusions The sMARIA is accurate and reliable in quantifying disease activity and response to treatment in luminal Crohn’s disease, without the need for gadolinium-enhanced sequences.
Published: 2020

32. Recomendaciones del Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) sobre el tratamiento tópico en la colitis ulcerosa

Author: Maria Esteve, Miguel Minguez, Eugeni Domènech, Elena Ricart, Ignacio Marín-Jiménez, Daniel Ginard, Manuel Barreiro-de Acosta, and Javier P. Gisbert
Subjects: 03 medical and health sciences, 0302 clinical medicine, Hepatology, business.industry, 030220 oncology & carcinogenesis, Gastroenterology, Medicine, 030211 gastroenterology & hepatology, business, Humanities
Abstract: Resumen Aunque un elevado porcentaje de pacientes con colitis ulcerosa deberia recibir tratamiento topico por via rectal, los estudios de practica clinica han demostrado que este esta infrautilizado. El proposito de este articulo es el de responder a 10 preguntas concretas sobre que farmacos estan disponibles para uso topico, su forma de presentacion, formulacion y metodos de aplicacion, asi como cual de ellos es mas eficaz e idoneo en los distintos escenarios clinicos de la colitis ulcerosa. Asimismo, se evalua la posibilidad de combinar diferentes formulaciones y vias de administracion, y la utilidad en la fase de remision de la enfermedad. Por ultimo, se hacen una serie de recomendaciones para una mejor informacion de los pacientes acerca de una correcta aplicacion y administracion.
Published: 2020

33. Risk Factors for COVID-19 in Inflammatory Bowel Disease: A National, ENEIDA-Based Case–Control Study (COVID-19-EII)

Author: Yamile, Zabana, Ignacio, Marín-Jiménez, Iago, Rodríguez-Lago, Isabel, Vera, María Dolores, Martín-Arranz, Iván, Guerra, Javier, P Gisbert, Francisco, Mesonero, Olga, Benítez, Carlos, Taxonera, Ángel, Ponferrada-Díaz, Marta, Piqueras, Alfredo, J Lucendo, Berta, Caballol, Míriam, Mañosa, Pilar, Martínez-Montiel, Maia, Bosca-Watts, Jordi, Gordillo, Luis, Bujanda, Noemí, Manceñido, Teresa, Martínez-Pérez, Alicia, López, Cristina, Rodríguez-Gutiérrez, Santiago, García-López, Pablo, Vega, Montserrat, Rivero, Luigi, Melcarne, María, Calvo, Marisa, Iborra, Manuel, Barreiro de Acosta, Beatriz, Sicilia, Jesús, Barrio, José Lázaro, Pérez Calle, David, Busquets, Isabel, Pérez-Martínez, Mercè, Navarro-Llavat, Vicent, Hernández, Federico, Argüelles-Arias, Fernando, Ramírez Esteso, Susana, Meijide, Laura, Ramos, Fernando, Gomollón, Fernando, Muñoz, Gerard, Suris, Jone, Ortiz de Zarate, José María, Huguet, Jordina, Llaó, Mariana Fe, García-Sepulcre, Mónica, Sierra, Miguel, Durà, Sandra, Estrecha, Ana, Fuentes Coronel, Esther, Hinojosa, Lorenzo, Olivan, Eva, Iglesias, Ana, Gutiérrez, Pilar, Varela, Núria, Rull, Pau, Gilabert, Alejandro, Hernández-Camba, Alicia, Brotons, Daniel, Ginard, Eva, Sesé, Daniel, Carpio, Montserrat, Aceituno, José Luis, Cabriada, Yago, González-Lama, Laura, Jiménez, María, Chaparro, Antonio, López-San Román, Cristina, Alba, Rocío, Plaza-Santos, Raquel, Mena, Sonsoles, Tamarit-Sebastián, Elena, Ricart, Margalida, Calafat, Sonsoles, Olivares, Pablo, Navarro, Federico, Bertoletti, Horacio, Alonso-Galán, Ramón, Pajares, Pablo, Olcina, Pamela, Manzano, Eugeni, Domènech, Maria, Esteve, On Behalf Of The Eneida Registry Of Geteccu, Universidad de Sevilla. Departamento de Medicina, Instituto de Salud Carlos III, FEDER (Fondo Europeo de Desarrollo Regional), [Zabana Y] Hospital Universitari Mútua Terrassa, Terrassa, Spain. Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain. [Marín-Jiménez I] Hospital Gregorio Marañón, Madrid, Spain. [Rodríguez-Lago I] Gastroenterology Department, Hospital Universitario de Galdakao, Galdakao, Spain. Biocruces Bizkaia Health Research Institute, Galdakao, Spain. [Vera I] Hospital Universitario Puerta de Hierro, Majadahonda, Spain. [Martín-Arranz MD] Hospital Universitario La Paz, Madrid, Spain. [Guerra I] Hospital Universitario de Fuenlabrada, Fuenlabrada, Spain. Instituto de Investigación Hospital Universitario La Paz (IdiPaz), Madrid, Spain. [Piqueras M, Mena R] Servei de Digestologia, Hospital de Terrassa, Consorci Sanitari de Terrassa, Terrassa, Spain, and Consorci Sanitari de Terrassa
Subjects: COVID-19, SARS-CoV-2, inflammatory bowel disease, 5-aminosalicylates, immunosuppression, Immunosupressió, Factors de risc en les malalties, Risk factors in diseases, terapéutica::terapia biológica::inmunomodulación::inmunoterapia::inmunosupresión [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS], Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [DISEASES], General Medicine, Inflammatory bowel diseases, COVID-19 (Malaltia), enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades del sistema digestivo::enfermedades gastrointestinales::enfermedades intestinales::enfermedad inflamatoria intestinal [ENFERMEDADES], Therapeutics::Biological Therapy::Immunomodulation::Immunotherapy::Immunosuppression [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT], Inflammatory bowel disease, Malalties inflamatòries intestinals, virosis::infecciones por virus ARN::infecciones por Nidovirales::infecciones por Coronaviridae::infecciones por Coronavirus [ENFERMEDADES], Digestive System Diseases::Gastrointestinal Diseases::Digestive System Diseases::Gastrointestinal Diseases::Intestinal Diseases::Inflammatory Bowel Diseases [DISEASES], Intestins - Inflamació, Immunosuppression
Abstract: COVID-19; Immunosuppression; Inflammatory bowel disease COVID-19; Immunosupressió; Malaltia inflamatòria intestinal COVID-19; Inmunosupresión; Enfermedad inflamatoria intestinal (1) Scant information is available concerning the characteristics that may favour the acquisition of COVID-19 in patients with inflammatory bowel disease (IBD). Therefore, the aim of this study was to assess these differences between infected and noninfected patients with IBD. (2) This nationwide case−control study evaluated patients with inflammatory bowel disease with COVID-19 (cases) and without COVID-19 (controls) during the period March−July 2020 included in the ENEIDA of GETECCU. (3) A total of 496 cases and 964 controls from 73 Spanish centres were included. No differences were found in the basal characteristics between cases and controls. Cases had higher comorbidity Charlson scores (24% vs. 19%; p = 0.02) and occupational risk (28% vs. 10.5%; p < 0.0001) more frequently than did controls. Lockdown was the only protective measure against COVID-19 (50% vs. 70%; p < 0.0001). No differences were found in the use of systemic steroids, immunosuppressants or biologics between cases and controls. Cases were more often treated with 5-aminosalicylates (42% vs. 34%; p = 0.003). Having a moderate Charlson score (OR: 2.7; 95%CI: 1.3−5.9), occupational risk (OR: 2.9; 95%CI: 1.8−4.4) and the use of 5-aminosalicylates (OR: 1.7; 95%CI: 1.2−2.5) were factors for COVID-19. The strict lockdown was the only protective factor (OR: 0.1; 95%CI: 0.09−0.2). (4) Comorbidities and occupational exposure are the most relevant factors for COVID-19 in patients with IBD. The risk of COVID-19 seems not to be increased by immunosuppressants or biologics, with a potential effect of 5-aminosalicylates, which should be investigated further and interpreted with caution.
Published: 2022

34. Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn's Disease: Real World Evidence From the ENEIDA Registry

Author: Diego Casas-Deza, Luis Javier Lamuela-Calvo, Fernando Gomollón, José Miguel Arbonés-Mainar, Berta Caballol, Javier P Gisbert, Montserrat Rivero, Eugenia Sánchez-Rodríguez, Lara Arias García, Ana Gutiérrez Casbas, Olga Merino, Lucía Márquez, Viviana Laredo, María Dolores Martín-Arranz, Pilar López Serrano, Sabino Riestra Menéndez, Carlos González-Muñoza, Luisa de Castro Parga, Marta Calvo Moya, Esteban Fuentes-Valenzuela, Maria Esteve, Marisa Iborra, Miguel Dura Gil, Manuel Barreiro-De Acosta, Rufo Humberto Lorente-Poyatos, Noemí Manceñido, Margalida Calafat, Iago Rodríguez-Lago, Jordi Guardiola Capo, Maria Antonia Payeras, Víctor Jair Morales Alvarado, Carlos Tardillo, Luis Bujanda, José Fernando Muñoz-Nuñez, Yolanda Ber Nieto, Fernando Bermejo, Pedro Almela, Mercè Navarro-Llavat, Pilar Martínez Montiel, Cristina Rodríguez Gutiérrez, Manuel Van Domselaar, Eva Sesé, Teresa Martínez Pérez, Elena Ricart, María Chaparro, María José García, Antonio López-Sanromán, Beatriz Sicilia, Beatriz Orts, Alicia López-García, Eduardo Martín-Arranz, José Lázaro Pérez-Calle, Ruth de Francisco, Esther García-Planella, Eugeni Domènech, and y Santiago García-López
Subjects: Crohn's disease, treatment, inflammatory bowel disease, Gastroenterology, General Medicine, elderly, ustekinumab
Abstract: Background and Aims Clinical trials and real-life studies with ustekinumab in Crohn’s disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. Methods Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey–Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. Results In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. Conclusions Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.
Published: 2022

35. I-CARE, a European Prospective Cohort Study Assessing Safety and Effectiveness of Biologics in Inflammatory Bowel Disease

Author: Laurent Peyrin-Biroulet, Jean-François Rahier, Julien Kirchgesner, Vered Abitbol, Sebastian Shaji, Alessandro Armuzzi, Konstantinos Karmiris, Javier P. Gisbert, Peter Bossuyt, Ulf Helwig, Johan Burisch, Henit Yanai, Glen A. Doherty, Fernando Magro, Tamás Molnar, Mark Löwenberg, Jonas Halfvarson, Edyta Zagorowicz, Hélène Rousseau, Cédric Baumann, Filip Baert, Laurent Beaugerie, Jean-Marc Gornet, Jean-Marie Reimund, Xavier Hebuterne, Aurélien Amiot, Franco Armelao, Pierre Blanc, Claudio Papi, Guillaume Pineton De Chambrun, Xavier Roblin, null Chu, Sohail Shariq, Nikolaos Viazis, Jimmy Limdi, Piotr Eder H, Georgios Michalopoulos, Andrew Bell, Livia Biancone, Marie Dewitte, Zia Mazhar, Denis Franchimont, Stephane Nancey, Gilles Macaigne, Maria Beatrice Principi, Mathurin Fumery, Gareth Parkes, Jean-Christophe Valats, Glen Doherty, Guillaume Bouguen, Hersin Tsai, Mohsin Gangi, Natalia Pedersen, Frédéric Heluwaert, Richard Shenderey, Sebastian Zeissig, Jeffrey Butterworth, Fabiana Castiglione, Lynsey Corless, Camille Zallot, Salil Singh, Sunil Sonwalkar, Elizabeth Clayton, Deven Vani, Guy Bellaiche, Martine De Vos, Uri Kopylov, Triana Lobaton, Christophe Locher, Gerassimos Mantzaris, George Abouda, Katie Smith, Michael Sprakes, Angeliki Theodoropoulou, Emma Wesley, Joëlle Bonnet, David Elphick, Cyrielle Gilletta, John Gordon, David Laharie, Antoine Nakad, Ambrogio Orlando, Patrick Dubois, Peter Hasselblatt, Christophe Michiels, Cathryn Preston, Anca Staicu, Lucine Vuitton, Mehdi Kaassis, Ally Speight, Deb Ghosh, Nicolas Mathieu, Anne-Laure Pelletier, Anne Phillips, Romain Altwegg, Irit Avni, null biron, Jonathon Landy, Maria Nachury, Achuth Shenoy, Caroline Trang, Georgios Bamias, Klaudia Farkas, Christian Maaser, Ariella Shitrit, Britta Siegmund, Jérôme Filippi, Colm O'morain, Laurent Costes, David Hobday, Zoltán Szepes, Emma Calabrese, Helen Dallal, Michael Fung, Arvind Ramadas, Bijay Baburajan, Konrad Koss, Christophe Barberis, Anthony Buisson, Morgane Amil, Paola Balestrieri, Matthew Johnson, Maria Tzouvala, Stéphanie Viennot, Ferenc Nagy, Nick Thompson, Laurent Alric, Sunil Samuel, Anne Bourrier, Elise Chanteloup, Emilie Del Tedesco, Marcus Harbord, Alan Lobo, Sally Myers, Richard Pollok, Tariq Ahmad, Rakesh Chaudhary, Christos Karakoidas, Ashraf Soliman, Carmen Stefanescu, Georgios Theocharis, Stijn Vanden Branden, Belén Beltran, Yoram Bouhnik, Arnaud Bourreille, Joana Branco, Ben Colleypriest, Rami Eliakim, Paul Knight, Aoibhlinn O'toole, Virgina Robles, Konstantinos Triantafyllou, Marta Maia Bosca, Guy Lambrecht, Lucia Marquez Mosquera, Simon Panter, Aikaterini Pappa, Marion Simon, Ganesh Sivaji, Christophe Bellanger, Arthur Belle, Natalia Borruel, Laurence Egan, Harald Peeters, Daniel Sharpstone, Ramesh Arasaradnam, José Manuel Benitez, Jens Frederik Dahlerup, Olga Giouleme, Miguel Minguez, Eftychia Tsironi, Angela Variola, Patrick Allen, Lucille Boivineau, Andy Cole, Nina Dib, Fernando Gomollon, Richard Johnston, Konstantinos Katsanos, Nick Kennedy, Marianne Kiszka-Kanowitz, Ignacio Marin-Jimenez, Pál Miheller, Pilar Nos, Othman Saraj, Lars Vinter-Jensen, Eran Zittan, Clotilde Baudry, Xavier Calvet, Marie-Christine Cazelles-Boudier, Jean-Louis Coenegrachts, Garret Cullen, Marco Daperno, Anjan Dhar, Romain Gerard, Nanna Jensen, Nitsan Maharshak, Mark Mcalindon, Simon Mcloughlin, Miles Parkes, Kamal Patel, Armando Peixoto, Dimitrios Polymeros, Francisco Portela, Rodolfo Rocca, Philippe Seksik, Sreedhar Subramanian, Ruth Tennenbaum, Raja Atreya, Oliver Bachmann, Arthur Berger, Renáta Bor, Maire Buckley, Daniel Carpio, María Chaparro, Francesco Costa, Eugeni Domenech, Maria Esteve, Stephen Foley, Jordi Guardiola, Ioannis Koutroubakis, Tanja Kuehbacher, Cécilia Landman, Alessandro Lavagna, Noemí Manceñido, Míriam Mañosa, Maria Dolores Martín-Arranz, Laurianne Plastaras, Maria Lia Scribano, Subhasish Sengupta, Nils Teich, My-Linh Tran-Minh, Evanthia Zampeli, Leila Amininejad, Teresa Arroyo, Alain Attar, Ann-Sofie Backman, Anita Bálint, John Beckly, Shomron Ben Horin, Sónia Bernardo, Ludovic Caillo, Bénédicte Caron, María Shanika de Silva, Anna FábiáN, Gionata Fiorino, Ana Gutierrez, Adi Lahat, Mohamed Masmoudi, Marco Mendolaro, Vinciane Muls, Florian Poullenot, Christopher Probert, Catherine Reenaers, Mariann Rutka, Zaman Sarwari, Joanne Sayer, Beatriz Sicilia, Helena Sousa, Catherine van Kemseke, Yamile Zabana, Marco Astegiano, Paul Banim, Dominik Bettenworth, Médina Boualit, Jacob Broder Brodersen, Angeliki Christidou, Rachel Cooney, João Cortez Pinto, Portugal Marília Cravo, Anneline Cremer, Silvio Danese, Antonio di Sabatino, Jan Fallingborg, Antonio Ferronato, Esther Garcia Planella, Sanjay Gupta, Eran Israeli, Samantha Kestenbaum, Lone Larsen, Elisabeth Macken, Nicoletta Mathou, Ágnes Milassin, Joanna Pofelski, Chiara Ricci, Francisco Rodriguez-Moranta, Martin Schmidt-Lauber, Ian Shaw, Marta Soares, Heithem Soliman, Christos Triantos, Konstantinos Zografos, Anurag Agrawal, Alexandre Aubourg, Manuel Barreiro-de Acosta, Jesús Barrio, Daniel Bergemalm, Fernando Bermejo, Giorgia Bodini, Johan Bohr, Dimitrios Christodoulou, Christophe Claessens, Paul Collins, Ruth de Francisco, Santiago Garcia, Sotirios Georgopoulos, Felix Goutorbe, Chrisostomos Kalantzis, Anastasia Kourikou, Vincent Mace, Georgia Malamut, Paula Ministro, Isabelle Nion Larmurier, Elena Ricart, Mélanie Serrero, Juliette Sheridan, Petra Weimers, Vibeke Andersen, Bruno Arroja, Bernd Bokemeyer, Luis Bujanda, Thibault Degand, Carl Eriksson, Cécile Garceau, Henning Glerup, Idan Goren, Lucina Jackson, Stéphane Koch, Francisco Mesonero, Ingrid Ordas, Pauline Riviere, Simone Saibeni, João Soares, Noémie Tavernier, Klaus Theede, Bella Ungar, Elke Bästlein, Antonio Gasbarrini, Andreas Protopapas, Wolfgang Reindl, Fabrizio Bossa, Ailsa Hart, Franz-Josef Heil, Anthony O'Connor, Bas Oldenburg, Luca Pastorelli, null Stephen patchett, Subramaniam Ramakrishnan, John de Caestecker, Ana Echarri, David Kevans, Jürgen Büning, Rosa Coelho, Jeroen Jansen, Benjamin Koslowski, Christopher Wells, Daniel Ceballos, Ingrid König, Hari Padmanabhan, Timi Patani, Raheel Qureshi, Matthieu Allez, Emmanouil Archavlis, Delphine Bonnet, Luisa Guidi, Deirdre Mcnamara, Piero Vernia, Michael Weidenhiller, Lang Alon, Trine Boysen, Charlotte Delattre, Richard Farrell, Rolf-Achim Krüger, Thierry Paupard, Ida Vind, Flavio Caprioli, Vladimir Gancho, Vincent Quentin, Benjamin Avidan, Geert D’Haens, Jane Mccarthy, Jonathon Snook, Konstantinos Soufleris, Frank Zerbib, Dan Carter, Annekatrien Depla, Thomas Eisenbach, Walter Fries, Nikolaos Grammatikos, Saskia Ilegems, Antonio Lopez-Sanroman, Jacques Moreau, Gabriele Riegler, Svend Rietdijk, Marta Rocha, Isabelle Rosa, Barbara Ryan, Yelena Yeremenko, Arnaud Boruchowicz, Filipe Damião, Foteini Laoudi, Andreas Lügering, Giampiero Macarri, Konstantinos Thomopoulos, Luísa Barros, Thomas Blixt, Aurélien Garros, Sam Khorrami, Harry Sokol, Andreas Sturm, Dan Livovsky, Jochen Maul, Heinrich Miks, Vasileios Papadopoulos, Carsten Schmidt, Yifat Snir, Lise Svenningsen, Wafaa Ahmed, Yelena Broitman, Emmanuel Cuillerier, Prashant Kant, Jan Leyden, Lev Lichtenstein, Susana Lopes, Chloé Martineau, Hugh Mulcahy, Axel Schweitzer, Fiona Van Schaik, Hagar Banai, Pauline Danion, Charlotte Dulery, Herma Fidder, Claire Gay, Hervé Hagege, Florence Harnois, Søren Peter Jørgensen, Jens Müller-Ziehm, Michail Oikonomou, Carolina Palmela, Jörg Schulze/Röske, Mark Smith, Tamar Thurm, Francesca Bresso, Hedia Brixi, John Jones, Padraig Macmathuna, Claire Painchart, Yulia Ron, Marianne Vester-Andersen, Gonçalo Alexandrino, Norbert Börner, Mariana Cardoso, Cristina Chagas, Axel Dignaß, Iris Dotan, Charlotte Hedin, Pantelis Karatzas, Panagiotis Kasapidis, Károly Palatka, Georgios Sakizlis, Ana Wilson, Nick Bosanko, Paulo Caldeira, Charlotte Gagniere, Louise Libier, Camille Meunier, Gero Moog, Audrey Pasquion, Roberta Pica, Ayesha Akbar, Nadia Arab, Guillaume Cadiot, João Carvalho, Claire Charpignon, Laus Fellermann, Sigal Fishman, Gerald Fraser, Nathan Gluck, Mark Hoesl, Jarosław Kierkus, Maria Klopocka, Eduardo Martin Arranz, Luis Menchen, Susanna Nikolaus, Anca Petrache, Cyriel Ponsioen, Sabino Riestra, Pilar Robledo, Cristina Rodriguez, Misheal Samer, Matthias Tischer, Joanna Wypych, Julien Baudon, Cristina Bezzio, Gilles Boschetti, Tom Creed, Maria Giulia Demarzo, Stefano Festa, Andrés Figueroa, Mette Julsgaard, Pablo Navarro, Pablo Perez-Galindo, Cléa Rouillon, Emanuele Sablich, Joan Tosca, Mathias Vidon, Marine Vidon, René-Louis Vitte, Anne Wampach, Isabelle Clerc Urmes, Marc Borie, Mathieu Uzzan, Kelly Chatten, Rimmer Peter, Iqbal Tariq, Marta Cossignani, Fiorella Cañete, Tom Holvoet, Susanne Krasz, Sandra Dias, Hadas Abalia, Aziza Abaza, Gal Abramovich, Ingrid Ackzell, Carol Adams, Catherine Addleton, Erika Alfambra, Alicia Algaba, Clare Allcock, Joanna Allison, Karine Amouriaux, Julie Anderson, Emma Anderson, Saskia Appelmans, Lisa Armstrong, Stacey Atkins, Masoumeh Attaran-Bandarabadi, Yvonne Bailey, Stephanie Bardot, Natasha Beck, Lillie Bennett, Jonathan Phil Bergfeld, Ramdane Berkane, Hanne Boey, Louise Bowlas, Joanne Bradley-Potts, Tracy Brear, Nicole Bretlander-Peters, Ellen Brown, Johanna Brown, Elizabeth Buckingham, Katrien Buellens, Rhian Bull, Maura Burke, Leighanne Burns, Julie Burton, Agness Bwalya, Karine Cabanas, Muriel Callaghan, Océane Camou, Debbie Campbell, Elvira Capoferro, Mandy Carnahan, Cornelia Carnio, Anne Carter, Concetta Casali Clack, Leïla Chedouba, Bessie Cipriano, Sophie Claeys, Manon Closset, Dilek Coban, Sara Cococcia, Carolann Coe, Helen Cole, Emilie Collet, Kayleigh Collins, Isabelle Combes, Emma Connor, Kathryn Constantin, Susan Cooke, Nathanaëlle Cornet, Estelle Corrihons, Pilar Corsino, Rosie Cortaville, Donna Cotterill, Amanda Cowton, Harriet Cox, Viktoria Cripps, Amanda Crowder, Tzufit Cukier, Amelia Daniel, Chris Dawe, Jose de Haan, Rosanna de la Croix, Evva Dejonckheere, Juan Delare Villanegro, Guillaume Delaval, Mariangela Delliponti, Aude Delommez, Emilie Detry, Melanie Dhanaratne, Laura Diez Galan, Marie Dodel, Emma Dooks, Joseph Du Cheyron, Linda Duane, Jennifer Dulling Vulgo Cochran, Simona Dyer, Harvey Dymond, Charlotte Ekblad, Kerry Elliott, Ingrid Emmerson, Irène Eugene-Jolchine, Lorna Fleming, Eve Fletcher, Sarah Ford, Greg Forshaw, Angela Foulds, Caroline Francois, Nicole Fuge, Gal Gafni, Miri Ganon, Olga Garcia Nuñez, Laura Garcia Ramirez, Sophie Gelder, Raimonda Gettkowski, Daniela Gilardi, Paolo Giuffrida, Vincent Gobert, Jo Godden, Nuala Godwin, Kay Goulden, Sharon Graham, Charlotte Green, Marie Green, Aboubakar Gueye, Tuba Guler, Ida Gustavsson, Helena Hadjisavvas, Fiona Hammonds, Christina Hantzi, Marion Hauke, Julie Haydock, Orla Hayes, Lizette Helbo Nislev, Jessica Hochstodter, Ashleigh Hogg, Manuela Hölbing, Maureen Holland, Maartje Holsbergen, Linda Howard, Aviya Hoyda, Robert Hull, Jane Irish, Wendy Jackson, Wendy Janssen, Lesley Jeffrey, Sofia Jourdan, Izabela Jutrowska, Chava Kaniel, Theofilos Karezos, Niamh Kelly, Jessica Kelly, Mary Kennedy, Una Kennedy, Joyce Kibaru, Gemma Kirkman, Janine Klaproth, Corinna Kneese, Andrea Koch, Kathleen Kokke, Martha Koppelow, Sabine Krause, Sabine Krauspe, Petra Kwakkenbos, Nunzia Labarile, Hannah Lang, Marianne Lassailly, Martine Leconte, Linda Lepczynski, Emma Levell, Nina Levhar, Kerstin Lindhort, Jessica Lisle, Beatriz Lopez Cauce, Gabriele Lorenz, Ambra Lovati, Tracey Lowry, Margareta Lund, Anne Lutz Vorderbrügge, Suzanne Maansson, Videsheka Madapathage, Maelys Cheviakoff, Alison Magness, Orla Manley, Catherine Manyoni, Ingke Marg, Antonella Marra, Carole Martins, Arianna Massella, Aurore Mathias, Danielle Mervyn, Charlotte Minsart, Sally Mitchell, Kathleen Monks, Mélanie Montero, Alson Moore, Maren Moser, Alison Moss, Angela Mullen, M. Francisca Murciano, Deanna Naylor, Ansgar Nehus, Anne Nicholson, Sarah Nöding, Sinead Nolan, Janet Nörenberg, Clare Northcott, Jim O'Connell, Alison O’Kelly, Noam Orbach-Zingboim, Judit Orobitg, Charlene Otieno, Charlotte Owen, Sarah Patch, Maor Pauker, Renate Pauli, Harriet Pearson, Falgon Peggy, Séverine Petit, Christine Petrissans, Simona Piergallini, Lucy Pippard, Laura Pitt, Gabriella Pócsik, Yoann Poher, Chloé Pomes, Lucy Pritchard, Laura Puchades, Sheena Quaid, Aleem Rana, Dana Raynard, Mykla Reilly, Sonja Reinert, Manuela Reinknecht, Baerbel Renner, Rob Reynolds, Giulia Rizzuto, Matthew Robinson, Joke Robrechts, Eva M. Rodriguez, Efrat Rosenblum, Tamlyn Russel, Ibiyemi Sadare, Noa Salama, Toos Schakel, Anja Schauer, Elisa Schiavoni, Caroline Shaw, Sarah Shelton, Virginie Sicart, Elodie Siouville, Orla Smith, Théo Soude, Sophie Stephenson, Elaine Stephenson, Marjan Steppe, An Sterkx, Jo Stickley, Kathleen Sugrue, Natalia Swietec, Charlotte Tasiaux, Bhavneet Thamu, Susane Thomas, Ogwa Tobi, Kahina Touabi, Shifra Tovi, Julie Tregonning, Laura Turchini, Julia Unkhoff, Olesya Unruh, Nurcan Uzun, Frauke Van Aert, Sandrine Vanden Bergh, Louise Vandenbroucke, Laura Vansteenkiste, Shay Vardit, Valentin Vergriete, Elaine Walker, Eleanor Warner, Olivia Watchorn, Ekaterina Watson, Marie-Claire Wauthier, Belgium Maria Weetman, Margaret Weston, Wiebke West-Petroschka, Susann Wienecke, Kerstin Wierling, Miriam Wiestler, Rebecca Wilcox, Elva Wilhelmsen, Angharad Williams, Georgina Williamson, Deborah Wilson, Kate Wistance, Nicolas Wortmann, Subie Wurie, Karin Yadgar, Gail Young, Megan Young, Julien Aucouturier, Marie- Jo Bertin, Hasnae Bougrine, Marie Coisnon, Antoine Defrance, Kati Gutierrez, Amel Harouz, Laure Jerber, Aida Khlifi, Amina Kirati, Nasaladjine Liworo, Maude Logoltat, Charlotte Mailhat, Chancely M'Bayi, Yasmina Medane, Dalal Merkhoufa, Saouda Mohamed Elhad, Bertille Monthe, Fanny Moyon, Pascaline Rabiega, Jennifer Sekela, Charlotte Thilloy, Naima Hamamouche, Frederic Partisotti, Patrick Blandin, Hocine Mokhtari, Laure Coutard, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Gastroenterology and hepatology, Gastroenterology and Hepatology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
Subjects: Biological Products, Hepatology, Efficacy, Lymphoma, Tumor Necrosis Factor-alpha, Inflammatory Bowel Disease, Gastroenterology, Biologics, Crohn Disease/diagnosis, Inflammatory Bowel Diseases/chemically induced, Colitis, Ulcerative/diagnosis, Cohort Studies, Necrosis, Immunologic Factors/adverse effects, Humans, Female, 03.02. Klinikai orvostan, Prospective Studies, Safety, I-CARE, Cancer, Immunosuppressive Agents
Abstract: BACKGROUND AND AIMS: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators.METHODS: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment.RESULTS: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia.CONCLUSIONS: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).
Published: 2022

36. Differentially Deregulated MicroRNAs as Novel Biomarkers for Neoplastic Progression in Ulcerative Colitis

Author: Isabel Quintanilla, Gerhard Jung, Mireya Jimeno, Juan José Lozano, Julia Sidorova, Jordi Camps, Sabela Carballal, Luis Bujanda, Maria Isabel Vera, Enrique Quintero, Marta Carrillo-Palau, Miriam Cuatrecasas, Antoni Castells, Julià Panés, Elena Ricart, Leticia Moreira, Francesc Balaguer, and Maria Pellisé
Subjects: Adenoma, MicroRNAs, Gastroenterology, Humans, Colitis, Ulcerative, Real-Time Polymerase Chain Reaction, Biomarkers
Abstract: INTRODUCTION: Colorectal cancer (CRC) is a potentially life-threatening complication of long-standing ulcerative colitis (UC). MicroRNAs (miRNA) are epigenetic regulators that have been involved in the development of UC-associated CRC. However, their role as potential mucosal biomarkers of neoplastic progression has not been adequately studied. METHODS: In this study, we analyzed the expression of 96 preselected miRNAs in human formalin-fixed and paraffin-embedded tissue of 52 case biopsies (20 normal mucosa, 20 dysplasia, and 12 UC-associated CRCs) and 50 control biopsies (10 normal mucosa, 21 sporadic adenomas, and 19 sporadic CRCs) by using Custom TaqMan Array Cards. For validation of deregulated miRNAs, we performed individual quantitative real-time polymerase chain reaction in an independent cohort of 50 cases (13 normal mucosa, 25 dysplasia, and 12 UC-associated CRCs) and 46 controls (7 normal mucosa, 19 sporadic adenomas, and 20 sporadic CRCs). RESULTS: Sixty-four miRNAs were found to be differentially deregulated in the UC-associated CRC sequence. Eight of these miRNAs were chosen for further validation. We confirmed miR-31, -106a, and -135b to be significantly deregulated between normal mucosa and dysplasia, as well as across the UC-associated CRC sequence (all P < 0.01). Notably, these miRNAs also confirmed to have a significant differential expression compared with sporadic CRC (all P < 0.05). DISCUSSION: UC-associated and sporadic CRCs have distinct miRNA expression patterns, and some miRNAs indicate early neoplastic progression. This work was funded by grants from the Instituto de Salud Carlos III (PI12/01481; PI19/01050). Project PI19/ 01050 is funded by Instituto de Salud Carlos III (ISCIII) and co funded by the European Union. CIBEREHD is funded by the Insti tuto de Salud Carlos III and Beca Marató de TV3 (201932-30). Parts of this work were also supported by the Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d’Oncología de Catalunya (XBTC) and by the Hospital Clínics Premi Fi de Residència (G.J). None of the funding parties has been involved in collection, analysis, and interpretation of the data.
Published: 2021

37. Editorial

Author: Santiago Mu�oz-Fern�ndez, Llu�s Puig, and Elena Ricart
Published: 2021

38. Hematopoietic Stem Cell Transplantation an Alternative to Treat Crohn's Disease

Author: Montserrat Rovira, Milton Artur Ruiz, Richard K. Burt, Roberto Luiz Kaiser, and Elena Ricart
Subjects: Crohn's disease, business.industry, medicine.medical_treatment, Immunology, medicine, Hematopoietic stem cell transplantation, medicine.disease, business
Published: 2021

39. Estricturotomía Endoscópica versus Dilatación Endoscópica con Balón para el tratamiento de las estenosis intestinales en la Enfermedad de Crohn

Author: Agnès Fernández-Clotet, Miriam Escapa, Begoña González-Suárez, Julià Panés, Angels Ginès, Berta Carballol, Gloria Fernández-Esparrach, Ingrid Ordás, Elena Ricart, and Antonio Giordano
Published: 2021

40. Avoiding contrast-enhanced sequences does not compromise the precision of the simplified MaRIA for the assessment of non-penetrating Crohn's disease activity

Author: Agnès Fernàndez-Clotet, Víctor Sapena, Nunzia Capozzi, Sonia Rodríguez, Maria-Carme Masamunt, Elena Ricart, Ingrid Ordás, Julian Panés, and Jordi Rimola
Subjects: Adult, Crohn Disease, Contrast Media, Humans, Radiology, Nuclear Medicine and imaging, Gadolinium, General Medicine, Prospective Studies, Magnetic Resonance Imaging
Abstract: Patients with Crohn's disease (CD) require multiple assessments with magnetic resonance enterography (MRE) from a young age. Standard MRE protocols for CD include contrast-enhanced sequences. Gadolinium deposits in brain tissue suggest avoiding gadolinium could benefit patients with CD. This study aimed to compare the accuracy of the simplified Magnetic Resonance Index of Activity (sMaRIA) calculated with and without contrast-enhanced sequences in determining the response to biologic drugs in patients with CD.This post hoc analysis of a prospective study included patients with CD with endoscopic ulceration in ≥ 1 intestinal segment starting biologic drug therapy. Two blinded radiologists used the sMaRIA to score images obtained at baseline and week 46 of treatment first using only unenhanced sequences (T2-sMaRIA) and 1 month later using both unenhanced and enhanced images (CE-sMaRIA). We calculated the rates of agreement between T2-sMaRIA, CE-sMaRIA, and ileocolonoscopy for different conceptualizations of therapeutic response.A total of 46 patients (median age, 36 years [IQR: 28-47]) were included. Agreement with ileocolonoscopy was similar for CE-sMaRIA and T2-sMaRIA in identifying ulcer healing (kappa = 0.74 [0.55-0.93] and 0.70 [0.5-0.9], respectively), treatment response (kappa = 0.53 [0.28-0.79] and 0.44 [0.17 - 0.71]), and remission (kappa = 0.48 [0.22-0.73] and 0.43 [0.17-0.69]). The standardized effect size was moderate for both CE-sMaRIA = 0.63 [0.41-0.85] p 0.001 and T2-sMaRIA = 0.58 [0.36-0.80] p 0.001.sMaRIA with and without contrast-enhanced images accurately classified the response according to different therapeutic endpoints determined by ileocolonoscopy.• The simplified Magnetic Resonance Index of Activity is accurate for the assessment of Crohn's disease activity, severity, and therapeutic response, using four dichotomic components that can be evaluated without the need of using contrast-enhanced sequences, representing a practical and safety advantage, but concerns have been expressed as to whether the lack of contrast sequences may compromise precision. • The simplified Magnetic Resonance Index of Activity can assess the response to biologic therapy in patients with Crohn's disease without the need for intravenous contrast agents obtaining comparable results without and with contrast-enhanced sequences. • Avoiding intravenous contrast agents could reduce the duration of the MRE examination and its cost and would increase the acceptance and safety of MRE in clinical research in patients with Crohn's disease.
Published: 2021

41. Endoscopic response to tumor necrosis factor inhibitors predicts long term benefits in Crohn’s disease

Author: Azucena Salas, Alejandro Vara, A. Giner, R. Barastegui, Marta Gallego, Elena Ricart, Ingrid Ordás, Ignacio Alfaro, Julián Panés, Alicia López-García, Maria Carme Masamunt, Jesús Castro, and Núria Planell
Subjects: Crohn’s disease, Male, Time Factors, Disease, Single Center, Severity of Illness Index, Gastroenterology, 0302 clinical medicine, Crohn Disease, Prospective Studies, Intestinal Mucosa, Crohn's disease, medicine.diagnostic_test, Mucosal healing, Area under the curve, Colonoscopy, General Medicine, Middle Aged, Prognosis, Treatment Outcome, 030220 oncology & carcinogenesis, Biomarker (medicine), Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Tumor necrosis factor alpha, Adult, medicine.medical_specialty, Tumor necrosis factor, Colon, Crohn’s Disease Endoscopic Index of Severity, Young Adult, 03 medical and health sciences, Gastrointestinal Agents, Ileum, Predictive Value of Tests, Internal medicine, medicine, Humans, Aged, Tumor Necrosis Factor-alpha, business.industry, Adalimumab, Endoscopy, medicine.disease, Infliximab, Prospective Study, business
Abstract: BACKGROUND Identifying predictors of therapeutic response is the cornerstone of personalized medicine. AIM To identify predictors of long-term mucosal healing (MH) in patients with Crohn’s disease (CD) treated with tumor necrosis factor α (TNF-α) inhibitors. METHODS Prospective single center study. Consecutive patients with clinically active CD requiring treatment with a TNF-α inhibitor were included. A baseline segmental CD Endoscopic Index of Severity (CDEIS) ≥ 10 in at least one segment or the presence of ulcerations were required for inclusion. Clinical, biological and endoscopic data were obtained at baseline, weeks 14 and 46. Endoscopic response (ER) was defined as a decrease ≥ 50% from baseline CDEIS and MH as partial CDEIS ≤ 5 in all segments. RESULTS Of 62 patients were included. At baseline, median CD Activity Index and CDEIS were 201 and 6.7, respectively with a significant reduction after one year of treatment (53 and 3.0 respectively, P < 0.001). At week 14, 56% of patients achieved ER and 34% MH. At week 46, the corresponding percentages were 52% and 44%. Baseline disease characteristics or biomarkers did not predict MH. A decrease from baseline CDEIS at week 14 of at least 80% was the best predictor of MH at week 46 (59% sensitivity and 91% specificity; area under the curve = 0.778). CONCLUSION Clinical and biomarker data are not useful predictors of response to TNF-α inhibitors in CD, whereas ER to induction therapy, defined as 80% reduction in global CDEIS, is a robust predictor of long-term MH. Achievement of this endoscopic endpoint may be considered as a therapeutic target for anti-TNF-α therapy.
Published: 2019

42. Dissecting common and unique effects of anti-alpha4beta7 and anti-tumor necrosis factor treatment in ulcerative colitis

Author: Julián Panés, Agnès Fernández-Clotet, Ana Maria Corraliza, Helena Bassolas-Molina, Maria Carme Masamunt, Eva Tristán, Montserrat Arroyes, Alba Garrido-Trigo, Miriam Esteller, Maria Esteve, Marisol Veny, Ingrid Ordás, Elena Ricart, and Azucena Salas
Subjects: Male, Integrins, Malalties de l'aparell digestiu, Necrosis, Biopsy, Inflammatory bowel disease, Gastroenterology, Medicine, Receptor, Gastroenterologia, biology, Antibodies, Monoclonal, General Medicine, α4β1, Middle Aged, Ulcerative colitis, Tumor necrosis factor alpha, Female, medicine.symptom, Antibody, medicine.drug, Adult, medicine.medical_specialty, αEβ7, Plasma Cells, Antibodies, Monoclonal, Humanized, Vedolizumab, Gastrointestinal Agents, inflammatory bowel disease, Colon, Sigmoid, Colitis ulcerosa, Internal medicine, Humans, Lymphocyte Count, AcademicSubjects/MED00260, business.industry, Tumor Necrosis Factor-alpha, Adalimumab, Original Articles, medicine.disease, Infliximab, Mechanism of action, Case-Control Studies, biology.protein, Colitis, Ulcerative, Digestive system diseases, business
Abstract: Background and AimsVedolizumab is an anti-α4β7 antibody approved for the treatment of ulcerative colitis [UC]. Although it is assumed that vedolizumab blocks intestinal homing of lymphocytes, its effects on different intestinal cell populations are not fully stablished. In order to establish the unique mechanisms of action of vedolizumab in UC patients, we compared its effects to those induced by anti-tumour necrosis factor [TNF].MethodsPatients with active UC [endoscopic Mayo score >1] starting vedolizumab [n = 33] or anti-TNF [n = 45] and controls [n = 22] were included. Colon biopsies [at weeks 0, 14 and 46] and blood samples [at weeks 0, 2, 6, 14, 30 and 46] were used for cell phenotyping, transcriptional analysis [qPCR], and to measure receptor occupancy.ResultsVedolizumab, in contrast to anti-TNF, significantly reduced the proportion of α4β7+ cells within intestinal T subsets while preserving the percentage of α4β7+ plasma cells. The marked decrease in α4β7 did not change the percentage of colonic αEβ7+ cells [at 46 weeks]. Both vedolizumab and anti-TNF significantly downregulated inflammation-related genes in the colon of responders [Mayo score < 2]. Moreover, both treatments significantly decreased the percentage of intestinal, but not blood, total lymphocytes [T and plasma cells], as well as the proportion of α4β1+ cells within intestinal T lymphocytes.ConclusionsOur data show that while vedolizumab and anti-TNF block two unrelated targets, they induce remarkably similar effects. On the other hand, vedolizumab’s unique mechanism of action relies on blocking intestinal trafficking of α4β7 T cells, despite effectively binding to B and plasma cells that express α4β7.
Published: 2021

43. Escenoterapia con niños y adolescentes

Author: Cacho, José Manuel Ibáñez, primary and Carratalá, Elena Ricart, additional
Published: 2014
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44. Effectiveness and Safety of Ustekinumab in Ulcerative Colitis: Real-world Evidence from the ENEIDA Registry

Author: María Chaparro, Ana Garre, Marisa Iborra, Mónica Sierra-Ausín, Manuel Barreiro-de Acosta, Agnès Fernández-Clotet, Luisa de Castro, Maia Boscá-Watts, María José Casanova, Alicia López-García, Rufo Lorente, Cristina Rodríguez, Ana Y Carbajo, Maria Teresa Arroyo, Ana Gutiérrez, Joaquín Hinojosa, Teresa Martínez-Pérez, Albert Villoria, Fernando Bermejo, David Busquets, Blau Camps, Fiorella Cañete, Noemí Manceñido, David Monfort, Mercè Navarro-Llavat, José Lázaro Pérez-Calle, Laura Ramos, Montserrat Rivero, Teresa Angueira, Patricia Camo Monterde, Daniel Carpio, Irene García-de-la-Filia, Carlos González-Muñoza, Luis Hernández, José M Huguet, Víctor J Morales, Beatriz Sicilia, Pablo Vega, Isabel Vera, Yamile Zabana, Pilar Nos, Patricia Suárez Álvarez, Cristina Calviño-Suárez, Elena Ricart, Vicent Hernández, Miguel Mínguez, Lucía Márquez, Daniel Hervías Cruz, Saioa Rubio Iturria, Jesús Barrio, Carla Gargallo-Puyuelo, Rubén Francés, Esther Hinojosa, María del Moral, Xavier Calvet, Alicia Algaba, Xavier Aldeguer, Jordi Guardiola, Miriam Mañosa, Ramón Pajares, Marta Piqueras, Orlando García-Bosch, Pilar López Serrano, Beatriz Castro, Alfredo J Lucendo, Miguel Montoro, Elena Castro Ortiz, Francisco Mesonero, Esther García-Planella, David A Fuentes, Inmaculada Bort, Pedro Delgado-Guillena, Lara Arias, Agueda Iglesias, Marta Calvo, Maria Esteve, Eugeni Domènech, and Javier P Gisbert
Subjects: Male, medicine.medical_specialty, ustekinumab, Vedolizumab, 03 medical and health sciences, 0302 clinical medicine, remission, Colitis ulcerosa, Internal medicine, Ustekinumab, Humans, Medicine, Prospective Studies, Registries, Infusions, Intravenous, Adverse effect, real-world evidence, AcademicSubjects/MED00260, ulcerative colitis, Tofacitinib, response, biology, business.industry, Remission Induction, C-reactive protein, Gastroenterology, General Medicine, Middle Aged, medicine.disease, Ulcerative colitis, Discontinuation, 030220 oncology & carcinogenesis, Cohort, biology.protein, durability, Original Article, Colitis, Ulcerative, Female, Monoclonal antibodies, 030211 gastroenterology & hepatology, business, Anticossos monoclonals, medicine.drug
Abstract: Background and Aims The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life. Methods Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16. Results A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusions Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.
Published: 2021

45. Evolution of Endoscopic Lesions in Steroid-Refractory Acute Severe Ulcerative Colitis Responding to Infliximab or Cyclosporine

Author: Arnaud Bourreille, Julien Branche, Laurent Beaugerie, Yoram Bouhnik, Stéphane Nahon, Mathurin Fumery, Benoit Coffin, Philippe Marteau, Matthieu Allez, Guillaume Savoye, Javier P. Gisbert, Martine De Vos, Jean-Yves Mary, Jacques Moreau, Elena Ricart, Laurent Peyrin-Biroulet, Xavier Roblin, Jérôme Filippi, Franck Carbonnel, Maria Esteve, Olivier Dewit, Aurelien Amiot, David Laharie, Martti Färkkilä, Lucine Vuitton, Anthony Buisson, Antonio López-Sanromán, Gert Van Assche, Frank Zerbib, CHU Bordeaux [Bordeaux], CIC Bordeaux, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Haut-Lévêque [CHU Bordeaux], Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Hôtel-Dieu de Nantes, Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Claude Huriez [Lille], CHU Lille, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7), Hôpital Beaujon [AP-HP], Centre Hospitalier Universitaire de Nice (CHU Nice), Hôpital l'Archet, Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNIROUEN - UFR Santé (UNIROUEN UFR Santé), Normandie Université (NU)-Normandie Université (NU), Service d'Hépato-Gastroentérologie [CHU Rouen], Hôpital Charles Nicolle [Rouen]-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU), Hôpital Charles Nicolle [Rouen], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Hôpital JeanMinjoz, CHU Toulouse [Toulouse], Hôpital Henri Mondor, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de Gastroentérologie et nutrition [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centro de Investigación Biomédica en Red en el Área temática de Enfermedades Hepáticas y Digestivas (CIBERehd), Liver Unit, Clínica Universitaria, CIBER-EHD, Université Catholique de Louvain = Catholic University of Louvain (UCL), Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), CHU Amiens-Picardie, Périnatalité et Risques Toxiques - UMR INERIS_I 1 (PERITOX), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service d'Hépato-gastro-entérologie [APHP Kremlin-Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris-Sud - Paris 11 (UP11), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Clermont Auvergne (UCA), Infection Inflammation et Interaction Hôtes Pathogènes [CHU Clermont-Ferrand] (3IHP ), Direction de la recherche clinique et de l’innovation [CHU Clermont-Ferrand] (DRCI), CHU Clermont-Ferrand-CHU Clermont-Ferrand, Hôpital Louis Mourier - AP-HP [Colombes], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Hôpital Nord (Saint Etienne), University Hospitals Leuven [Leuven], University of Helsinki, CHU Tenon [AP-HP], Sorbonne Université (SU), Groupe Hospitalier Intercommunal Le Raincy-Montfermeil, Ghent University Hospital, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Equipe 2 : ECSTRA - Epidémiologie Clinique, STatistique, pour la Recherche en Santé (CRESS - U1153), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Department of Medicine, Gastroenterologian yksikkö, Helsinki University Hospital Area, Hôpital Archet 2 [Nice] (CHU), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Service de Gastro-Entérologie [CHRU Besançon], Service de Gastro-entérologie et Nutrition[Rangueil], CHU Toulouse [Toulouse]-Hôpital de Rangueil, Service de gastro-entérologie [Henri Mondor AP-HP, Créteil], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), Hospital Clínic de Barcelona, Cliniques Universitaires Saint-Luc [Bruxelles], Service d'Hépato Gastroenterologie [CHU Amiens-Picardie], Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie-Institut National de l'Environnement Industriel et des Risques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service d'Hépato-gastroentérologie [CHU Saint-Etienne], Hospital Universitario Mutua de Terrassa, Helsinki University Central Hospital [Finland] (HUCH), Universidad Autonoma de Madrid (UAM), Hospital Universitario de la Princesa, Service d'Hépato-gastro-entérologie [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Hépato-gastro-entérologie [CHRU Nancy], Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Association Francois Aupetit, CHU Rouen, Pôle Maladies de l'appareil digestif [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Hépatologie Gastro-entérologie [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), DESSAIVRE, Louise, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
Subjects: medicine.medical_specialty, MAINTENANCE THERAPY, UCEIS, [SDV]Life Sciences [q-bio], Gastroenterology, Severity of Illness Index, Mucosal Healing, law.invention, Vedolizumab, 03 medical and health sciences, 0302 clinical medicine, Maintenance therapy, Randomized controlled trial, law, Interquartile range, VEDOLIZUMAB, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, INDEX, OUTCOMES, Hepatology, business.industry, ulcerative Colitis, INDUCTION, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, REMISSION, medicine.disease, Ulcerative colitis, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Infliximab, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, 3121 General medicine, internal medicine and other clinical medicine, Cyclosporine, 030211 gastroenterology & hepatology, Colitis, Ulcerative, Steroids, business, Steroid refractory, medicine.drug
Abstract: International audience; BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS >= 6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p
Published: 2021

46. A Novel Strategy to Study the Invasive Capability of Adherent-Invasive Escherichia coli by Using Human Primary Organoid-Derived Epithelial Monolayers

Author: Queralt Bonet-Rossinyol, Isabella Dotti, Marta Martínez-Picola, Azucena Salas, Miriam Esteller, Margarita Martinez-Medina, Aida Mayorgas, Elena Ricart, and Agencia Estatal de Investigación
Subjects: 0301 basic medicine, lcsh:Immunologic diseases. Allergy, Immunology, Biology, Crohn, Malaltia de, Sistema immunològic, Microbiology, Pathogenesis, 03 medical and health sciences, 0302 clinical medicine, Immune system, Organoid, Escherichia coli, Immunology and Allergy, Pathogen, organoid-derived epithelial monolayers (ODM), bacterial infection, intestinal epithelial cells (IECs), Intestinal epithelium, inflammatory bowel disease (IBD), 3. Good health, Crohn, Malaltia de -- Patogènesi, Crohn's disease, Crohn's disease -- Pathogenesis, 030104 developmental biology, adherent-invasive E. coli (AIEC), Escheríchia coli, Cell culture, 030211 gastroenterology & hepatology, lcsh:RC581-607, Immortalised cell line, Intracellular
Abstract: Over the last decades, Adherent-Invasive Escherichia coli (AIEC) has been linked to the pathogenesis of Crohn’s Disease. AIEC’s characteristics, as well as its interaction with the gut immune system and its role in intestinal epithelial barrier dysfunction, have been extensively studied. Nevertheless, the currently available techniques to investigate the cross-talk between this pathogen and intestinal epithelial cells (IECs) are based on the infection of immortalized cell lines. Despite their many advantages, cell lines cannot reproduce the conditions in tissues, nor do they reflect interindividual variability or gut location-specific traits. In that sense, the use of human primary cultures, either healthy or diseased, offers a system that can overcome all of these limitations. Here, we developed a new infection model by using freshly isolated human IECs. For the first time, we generated and infected monolayer cultures derived from human colonic organoids to study the mechanisms and effects of AIEC adherence and invasion on primary human epithelial cells. To establish the optimal conditions for AIEC invasion studies in human primary organoid-derived epithelial monolayers, we designed an infection-kinetics study to assess the infection dynamics at different time points, as well as with two multiplicities of infection (MOI). Overall, this method provides a model for the study of host response to AIEC infections, as well as for the understanding of the molecular mechanisms involved in adhesion, invasion and intracellular replication. Therefore, it represents a promising tool for elucidating the cross-talk between AIEC and the intestinal epithelium in healthy and diseased tissues AM was supported by the Programa Estatal de Investigación, Desarrollo e Innovación del Ministerio de Economía, Industria y Competitividad, co-funded by the European Social Fund (ESF) under grant agreement number FPI BES-2016-076642. ID is funded by the Horizon 2020 Framework Programme (EU for Research and Innovation H2020), Grant 720905. QB-R was supported by the Programa d’Ajuts per a Investigadors en Formació de la Universitat de Girona – IFUdG 2019/21. AS is funded by the Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD) and Grant RTI2018- 096946-B-I00 from the Ministerio de Ciencia, Innovación y Universidades, Spain. MM-M is funded by the Spanish Ministry of Economy and Competitiveness through project SAF2017-82261-P, which is co-funded by the European Regional Development Fund
Published: 2021

47. Pre-treatment magnetic resonance enterography findings predict the response to TNF-alpha inhibitors in Crohn's disease

Author: Julián Panés, Jordi Rimola, Ingrid Ordás, Sònia Rojas-Farreras, Sonia Rodríguez, Elena Ricart, Agnès Fernández-Clotet, Nunzia Capozzi, Ignacio Alfaro, and Maria-Carme Masamunt
Subjects: Pre treatment, Adult, Male, medicine.medical_specialty, Time Factors, Colon, Anti-Inflammatory Agents, Disease, Gastroenterology, Severity of Illness Index, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Ileum, Internal medicine, Medicine, Humans, Immunologic Factors, Pharmacology (medical), 030212 general & internal medicine, Longitudinal Studies, Prospective Studies, Aged, Crohn's disease, Hepatology, business.industry, Tumor Necrosis Factor-alpha, Middle Aged, medicine.disease, Magnetic resonance enterography, Prognosis, Magnetic Resonance Imaging, Intestines, Treatment Outcome, 030211 gastroenterology & hepatology, Tumor necrosis factor alpha, Female, business, human activities
Abstract: Identifying predictors of therapeutic response is the cornerstone of personalised medicine.To identify predictors of long-term healing of severe inflammatory lesions based on magnetic resonance enterography (MRE) findings in patients with Crohn's disease (CD) treated with tumour necrosis factor alpha (TNF-α) inhibitors.This prospective longitudinal single-centre study included patients with clinically active CD requiring treatment with TNF-α inhibitors with at least one intestinal segment with a severe inflammatory lesion detected by MRE (segmental MaRIA ≥11). MRE data were obtained at baseline, and at weeks 14 and 46. The primary endpoint was healing of severe inflammatory lesions (MaRIA11) in each segment. The secondary endpoint was healing of all severe inflammatory lesions on a per-patient analysis.We included 58 patients with 86 intestinal segments with severe inflammatory lesions. At week 46, healing of severe lesions was found in 51/86 (59.3%) segments, and complete healing of inflammatory lesions in all segments was found in 28/58 (48.6%) patients. Multivariable analysis found baseline-negative predictors of long-term healing of severe inflammation were ileal (as opposed to colonic) location (OR 0.00, [0.00-0.56] P = 0.002) and presence of creeping fat on MRE (OR 0.00 [0.00-0.57]; P = 0.001). Persistence of segmental MaRIA score10.6 at week 14 was a negative predictor of healing at week 46 (OR 0.3 [0.04--0.38]; P 0.001).In patients with CD, the absence of creeping fat detected at baseline MRE and location of severe inflammatory lesions are clinically relevant predictors of long-term healing of severe inflammation under treatment with TNF-α inhibitors.
Published: 2020

48. Multi-omic modelling of inflammatory bowel disease with regularized canonical correlation analysis

Author: Anna Carrasco, Aida Mayorgas, Dirk Haller, Maria Esteve, Eva Tristán, Ana Maria Corraliza, Elena Ricart, A. Salas, Amira Metwaly, Julián Panés, Lluís Revilla, Juan José Lozano, and Maria Carme Masamunt
Subjects: 0301 basic medicine, Male, Multivariate analysis, Computer science, Cell Transplantation, Biopsy, Datasets as Topic, Crohn's Disease, Pathogenesis, Pathology and Laboratory Medicine, Inflammatory bowel disease, 0302 clinical medicine, Transcripció genètica, Medicine and Health Sciences, Blood and Lymphatic System Procedures, Gliomas, Neurological Tumors, Hyperparameter, Multidisciplinary, Genetic transcription, Hematopoietic Stem Cell Transplantation, Genomics, Glioma, Explained variation, Oncology, Neurology, Medical Microbiology, Generalized canonical correlation, Host-Pathogen Interactions, Medicine, 030211 gastroenterology & hepatology, Female, Canonical correlation, Transcriptome Analysis, Research Article, Adult, Adolescent, Science, Immunology, Microbiota intestinal, Surgical and Invasive Medical Procedures, Computational biology, Microbial Genomics, Gastroenterology and Hepatology, Biology, Microbiology, Autoimmune Diseases, 03 medical and health sciences, Young Adult, Hematopoesi, medicine, Genetics, Humans, Microbiome, Gastrointestinal microbiome, Transplantation, business.industry, Model selection, Inflammatory Bowel Disease, Biology and Life Sciences, Computational Biology, Cancers and Neoplasms, medicine.disease, Inflammatory Bowel Diseases, Genome Analysis, Hematopoiesis, Gastrointestinal Microbiome, Data set, 030104 developmental biology, Multivariate Analysis, Clinical Immunology, Personalized medicine, Clinical Medicine, business, Transcriptome, Stem Cell Transplantation
Abstract: Background Personalized medicine requires finding relationships between variables that influence a patient’s phenotype and predicting an outcome. Sparse generalized canonical correlation analysis identifies relationships between different groups of variables. This method requires establishing a model of the expected interaction between those variables. Describing these interactions is challenging when the relationship is unknown or when there is no pre-established hypothesis. Thus, our aim was to develop a method to find the relationships between microbiome and host transcriptome data and the relevant clinical variables in a complex disease, such as Crohn’s disease. Results We present here a method to identify interactions based on canonical correlation analysis. We show that the model is the most important factor to identify relationships between blocks using a dataset of Crohn’s disease patients with longitudinal sampling. First the analysis was tested in two previously published datasets: a glioma and a Crohn’s disease and ulcerative colitis dataset where we describe how to select the optimum parameters. Using such parameters, we analyzed our Crohn’s disease data set. We selected the model with the highest inner average variance explained to identify relationships between transcriptome, gut microbiome and clinically relevant variables. Adding the clinically relevant variables improved the average variance explained by the model compared to multiple co-inertia analysis. Conclusions The methodology described herein provides a general framework for identifying interactions between sets of omic data and clinically relevant variables. Following this method, we found genes and microorganisms that were related to each other independently of the model, while others were specific to the model used. Thus, model selection proved crucial to finding the existing relationships in multi-omics datasets.
Published: 2020
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49. INTRALESIONAL INJECTION OF ADALIMUMAB IN INTESTINAL STRICTURES OF PATIENTS WITH CROHN’S DISEASE: A RANDOMIZED, MULTICENTER, PROSPECTIVE CLINICAL TRIAL

Author: A Giordano, Lidia Argüello, A Gutiérrez, Begoña González-Suárez, Yago González Lama, CH Nadal, Carlos Romero, Lucía Márquez, Ana Echarri, Sam Khorrami, Julián Panés, Elena Ricart, and M D Martín Arranz
Subjects: Clinical trial, medicine.medical_specialty, Crohn's disease, business.industry, Internal medicine, medicine, Adalimumab, business, medicine.disease, Gastroenterology, medicine.drug
Published: 2020

50. Switching to a Second Thiopurine in Adult and Elderly Patients With Inflammatory Bowel Disease: A Nationwide Study From the ENEIDA Registry

Author: Margalida, Calafat, Míriam, Mañosa, Francisco, Mesonero, Jordi, Guardiola, Miguel, Mínguez, Pilar, Nos, Isabel, Vera, Carlos, Taxonera, Eva, Iglesias, Elena, Ricart, Javier P, Gisbert, Xavier, Calvet, Santiago, García-López, David, Monfort, José Lázaro, Pérez Calle, Sabino, Riestra, Fernando, Gomollón, Esther, Garcia-Planella, Fernando, Bermejo, Vicent, Hernández, María Dolores, Martín-Arranz, Ana, Gutiérrez, Paola, Torres, Fiorella, Cañete, Eugeni, Domènech, and Zabana, Yamile
Subjects: Adult, Male, medicine.medical_specialty, Drug-Related Side Effects and Adverse Reactions, Concordance, Inflammatory bowel disease, elderly, 03 medical and health sciences, 0302 clinical medicine, inflammatory bowel disease, Internal medicine, Azathioprine, medicine, Humans, 030212 general & internal medicine, Practice Patterns, Physicians', Adverse effect, Thiopurine, elderly, inflammatory bowel disease, Aged, Thiopurine methyltransferase, biology, Thiopurine, business.industry, Drug Substitution, Mercaptopurine, Gastroenterology, Age Factors, General Medicine, Odds ratio, Drug Tolerance, medicine.disease, Inflammatory Bowel Diseases, Confidence interval, digestive system diseases, Clinical Practice, Spain, biology.protein, Acute pancreatitis, 030211 gastroenterology & hepatology, Female, Risk Adjustment, Drug Monitoring, business, Immunosuppressive Agents
Abstract: Background and Aims Although commonly used in inflammatory bowel disease [IBD], thiopurines frequently cause intolerance, and switching to a second thiopurine has only been reported in some small series. Ours aims in this study were to evaluate the safety of switching to a second thiopurine in a large cohort, and to assess the impact of age on tolerance. Methods Adult IBD patients from the ENEIDA registry, who were switched to a second thiopurine due to adverse events [excluding malignancies and infections], were identified. At the beginning of thiopurine treatment, patients were divided by age into two groups: 18–50 and over 60 years of age. The rate and concordance of adverse events between the first and second thiopurines, treatment intolerance, and persistence with the second thiopurine were evaluated. Results A total of 1278 patients [13% over 60 years of age] were switched to a second thiopurine. At 12 months, the cumulative probability of switch intolerance was 43%, and persistence with treatment was 49%. Independent risk factors of switch intolerance were age over 60 years (odds ratio [OR] 1.49; 95% confidence interval [CI] 1.07–2.07; p = 0.017) , previous gastrointestinal toxicity [OR 1.4; 95% CI 1.11–1.78; p = 0.005], previous acute pancreatitis [OR 6.78; 95% CI 2.55–18.05; p Conclusions In a large series in clinical practice, switching to a second thiopurine proved to be a valid strategy. Tight monitoring of elderly IBD patients switching to a second thiopurine because of adverse events is recommended.
Published: 2020

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