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Resumen Introduccion La capsula endoscopica de intestino delgado (CEID) es una tecnica diagnostica poco invasiva cuyo empleo en la enfermedad inflamatoria intestinal (EII) se ha extendido. Se ha desarrollado recientemente una capsula panenterica, PillCamCrohn's (PCC). Carecemos de informacion sobre la disponibilidad y el uso de la CEID y la PCC en nuestro medio. Metodos Realizamos una encuesta electronica y anonima entre los miembros del Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa y la Asociacion Espanola de Gastroenterologia consistente en 37 preguntas de respuesta multiple. Resultados Participaron 150 miembros, la mayoria con dedicacion especial a la EII (69,3%). El 72,8% trabajaban en centros con unidad de EII. El 79% tenian la CEID disponible en su hospital, y el 14% la derivaban a otro centro. El 22% tenian disponible la PCC, y el 9% la derivaban a otro centro. El 79,3% de encuestados con CEID disponible la utilizaban en un pequeno porcentaje de pacientes con EII y el 15,6% en la mayoria. Los escenarios mas frecuentes fueron la sospecha de enfermedad de Crohn (76,3%), la valoracion de actividad inflamatoria (54,7%) y la evaluacion de la extension de la enfermedad (54,7%). Mas de la mitad (59,7%) utilizaban preferentemente la capsula Patency® para valoracion de la permeabilidad intestinal. Casi todos los encuestados (99,3%) consideraban que se deberian implementar recursos formativos en esta tecnica. Conclusiones La CEID cuenta con una amplia disponibilidad en los hospitales espanoles para el manejo de la EII, si bien su uso es todavia limitado. Existe una oportunidad para aumentar la formacion en esta tecnica, y, con ella, su empleo.

BACKGROUND Crohn's disease (CD) with upper gastrointestinal involvement (UGI) may have a more aggressive and refractory course. However, evidence on this phenotype of patients is scarce. AIMS To identify the clinical characteristics, therapeutic requirements and complications associated with UGI in CD METHODS: Nationwide study of cases (UGI, UGI plus ileal/ileocolonic involvement) paired with controls (ileal/ileocolonic involvement) from the ENEIDA registry. Cases were matched to 2 controls by year of diagnosis ± 2.5 years. Patients with exclusive/predominant colonic location or complex perianal fistula were excluded. RESULTS Of 24 738 patients with CD in the ENEIDA registry, we identified 4058 with UGI (16% of the total CD cohort). Finally, 854 cases and 1708 controls were included. Cases were independently associated to extensive involvement (OR 2.7 [2.2-3.3], P

Colonic inflammatory bowel diseases have a higher risk of developing colorectal cancer compared to the general population, which is why they require endoscopic screening techniques with specific follow-up intervals based on the different risk factors described on the literature. This position paper analyzes the current scientific evidence for the different endoscopic techniques available today, how their implementation should be carried out in endoscopic units and describes in detail how their implementation should be carried out, in which patients and with what interval, and finally, what should be the response to finding dysplasia, proposing a specific follow-up algorithm.

Resumen Los pacientes con enfermedades inflamatorias intestinales de localizacion colonica tienen mayor riesgo de desarrollar cancer colorrectal que la poblacion general, por lo que precisan de tecnicas endoscopicas de cribado con intervalos de seguimiento basados en los diferentes factores de riesgo descritos. En el presente documento de posicionamiento analizamos la evidencia cientifica vigente para las diferentes tecnicas endoscopicas disponibles en la actualidad, como debe realizarse su implementacion en las unidades de endoscopia, y se describe con detalle como debe ser tecnicamente su realizacion, a que pacientes y con que intervalo debe realizarse, y finalmente, cual debe ser nuestra actitud ante el hallazgo de displasia, proponiendo un algoritmo de seguimiento especifico.

espanolLa ecografia tiene un excelente rendimiento diagnostico tanto cuando se sospecha una enfermedad de Crohn como en la valoracion de la actividad o en determinar su extension y localizacion, muy similar a otras exploraciones como resonancia magnetica o tomografia computarizada. Tiene una buena correlacion con las lesiones endoscopicas y permite la deteccion de complicaciones como estenosis, fistulas o abscesos. Complementa a la colonoscopia en el diagnostico y dada su tolerancia, coste e inmediatez, es una buena herramienta para la monitorizacion de la enfermedad. En la colitis ulcerosa su papel es menos relevante, limitandose a valorar la extension y actividad cuando no sea posible o haya dudas con otras tecnicas diagnosticas. A pesar de sus ventajas, su empleo en la enfermedad inflamatoria intestinal (EII) no esta muy extendido en nuestro pais. Por este motivo, el presente documento revisa las virtudes e inconvenientes de la tecnica para favorecer su conocimiento e implantacion en las Unidades de EII. EnglishUltrasound has an excellent diagnostic performance when Crohn's disease is suspected, when performing an activity assessment, or determining the extension and location of Crohn's disease, very similar to other examinations such as MRI or CT. It has a good correlation with endoscopic lesions and allows the detection of complications such as strictures, fistulas or abscesses. It complements colonoscopy in the diagnosis and, given its tolerance, cost and immediacy, it can be considered as a good tool for disease monitoring. In ulcerative colitis, its role is less relevant, being limited to assessing the extent and activity when it is not possible with other diagnostic techniques or if there are doubts with these. Despite its advantages, its use in inflammatory bowel disease (IBD) is not widespread in Spain. For this reason, this document reviews the advantages and disadvantages of the technique to promote knowledge about it and implementation of it in IBD Units.

Resumen La evidencia de que el seguimiento de las recomendaciones sobre el cribado y tratamiento de la infeccion tuberculosa no evita totalmente la aparicion de tuberculosis en pacientes con enfermedad inflamatoria intestinal, y el uso reciente de nuevos farmacos biologicos y de nuevos inmunomoduladores, ha llevado al Grupo Espanol de Trabajo en Enfermedad de Crohn y en Colitis Ulcerosa a actualizar sus recomendaciones para la prevencion de la tuberculosis en los pacientes con enfermedad inflamatoria intestinal. Se revisan los metodos de diagnostico de la infeccion tuberculosa latente, los distintos escenarios en los que se va a realizar el cribado, las estrategias para disminuir el riesgo de tuberculosis una vez iniciado el tratamiento biologico, las pautas de quimioprofilaxis de la infeccion tuberculosa latente y el manejo de la tuberculosis activa durante el tratamiento biologico. Finalmente, se resumen las recomendaciones en el texto y en un algoritmo.

Crohn's disease (CD) is a complex and multifactorial illness. There are still considerable gaps in our knowledge regarding its pathophysiology. A transcriptomic approach could shed some light on little-known biological alterations of the disease. We therefore aimed to explore the ileal transcriptome to gain knowledge about CD. We performed whole transcriptome gene expression analysis on ileocecal resections from CD patients and inflammatory bowel disease-free controls, as well as on a CD-independent cohort to replicate selected results. Normalized data were hierarchically clustered, and gene ontology and the molecular network were studied. Cell cultures and molecular methods were used for further evaluations. Genome-wide expression data analysis identified a robust transmembrane immunoglobulin domain-containing 1 (TMIGD1) gene underexpression in CD tissue, which was even more marked in inflamed ileum, and which was replicated in the validation cohort. Immunofluorescence showed TMIGD1 to be located in the apical microvilli of well-differentiated enterocytes but not in intestinal crypt. This apical TMIGD1 was lower in the noninflamed tissue and almost disappeared in the inflamed mucosa of surgical resections. In vitro studies showed hypoxic-dependent TMIGDI decreased its expression in enterocyte-like cells. The gene enrichment analysis linked TMIGD1 with cell recovery and tissue remodeling in CD settings. involving guanylate cyclase activities. Transcriptomics may be useful for finding new targets that facilitate studies of the CD pathology. This is how TMIGD1 was identified in CD patients, which was related to multiciliate ileal epithelial cell differentiation. NEW & NOTEWORTHY This is a single-center translational research study that aimed to look for key targets involved in Crohn's disease and define molecular pathways through different functional analysis strategies. With this approach, we have identified and described a novel target, the almost unknown TMIGD1 gene, which may be key in the recovery of injured mucosa involving intestinal epithelial cell differentiation.

Resumen Introduccion Desde la publicacion de la primera edicion de la Guia en 2013, se ha generado mucha informacion en torno al tratamiento de la colitis ulcerosa, y se han introducido nuevos farmacos y protocolos de actuacion. La practica clinica ha variado substancialmente, lo que justifica nuevas aproximaciones y una revision exhaustiva, asi como la actualizacion de la evidencia. Material y metodos Se utiliza nuevamente metodologia GRADE, apoyados en una herramienta electronica ( https://gradepro.org ). Los escenarios clinicos son los mismos que en la version previa (induccion y mantenimiento en brote grave y en brote leve-moderado), asi como las variables y su evaluacion. En la guia actualizada, en relacion a la version previa, se eliminan tres preguntas, se anaden 14 y se mantienen 30, con un total de 44 preguntas clinicas. Tras una exhaustiva revision de la evidencia, se actualizan las recomendaciones. Resultados De las 44 preguntas analizadas, en dos de ellas no se ha podido establecer ninguna recomendacion por muy baja calidad de la evidencia, mientras que en las 42 restantes, basados en diferentes grados de calidad de evidencia, se ha formulado una recomendacion de acuerdo con el sistema GRADE. En 25 de estas preguntas la recomendacion final es fuerte a favor; en seis, fuerte en contra; mientras que en siete es debil a favor, y en cuatro debil en contra. Siguiendo los escenarios y las recomendaciones, se proponen seis algoritmos como guia sencilla en la toma de decisiones practicas. Conclusiones Esta actualizacion de la guia previa publicada en 2013 intenta dar respuesta basada en la metodologia GRADE a las diferentes preguntas que nos hacemos diariamente a la hora de decidir el tratamiento mas adecuado de nuestros pacientes con colitis ulcerosa en los diferentes escenarios clinicos.

Background and aims Crohn’s disease [CD] can develop penetrating complications at any time during the disease course. Enterocutaneous fistulae [ECF] are disease-related complications with an important impact on quality of life. Our aim was to describe the outcomes of this complication, including its medical and/or surgical management and their temporal trends. The primary endpoint was fistula closure, defined as the absence of drainage, with no new abscess or surgery, over the preceding 6 months. Methods Clinical information from all adult patients with CD and at least one ECF—excluding perianal fistulae—were identified from the prospectively-maintained ENEIDA registry. All additional information regarding treatment for this complication was retrospectively reviewed. Results A total of 301 ECF in 286 patients [January 1970-September 2020] were analysed out of 30 088 records. These lesions were mostly located in the ileum [67%] and they had a median of one external opening [range 1-10]. After a median follow-up of 146 months (interquartile range [IQR], 69-233), 69% of patients underwent surgery. Fistula closure was achieved in 84%, mostly after surgery, and fistula recurrence was uncommon [13%]. Spontaneous and low-output fistulae were associated with higher closure rates (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.17-1.93, p = 0.001, and HR 1.49, 95% CI 1.07-2.06, p = 0.03, respectively); this was obtained more frequently with medical therapy since biologics have been available. Conclusions ECF complicating CD are rare but entail a high burden of medical and surgical resources. Closure rates are high, usually after surgery, and fistula recurrence is uncommon. A significant proportion of patients receiving medical therapy can achieve fistula closure.

BACKGROUND: Anti-TNF agents are the only effective biological agents for the prevention of postoperative recurrence (POR) in Crohn's disease (CD). However, they are contraindicated or have been shown to fail in some patients. Although ustekinumab and vedolizumab were licensed for CD some years ago, data in this setting are scarce.; METHODS: All CD patients in whom ustekinumab or vedolizumab was prescribed for the prevention of POR within three months of ileocolonic resection with anastomosis were identified from the ENEIDA registry. The development of endoscopic, clinical and surgical POR was registered.; RESULTS: Forty patients were treated for the prevention of POR with ustekinumab and 25 were treated with vedolizumab. Eighty per cent had at least one risk factor for POR (prior resections, active smoking, perianal disease or penetrating disease behaviour). All the patients had been exposed to anti-TNF therapy. After a median follow-up of 17 and 26 months, the cumulative probability of clinical POR at 12 months after surgery was 32% and 30% for ustekinumab and vedolizumab, respectively. Endoscopic assessment within the first 18 months after surgery was available for 80% of the patients on ustekinumab and 70% for those on vedolizumab. The rate of endoscopic POR was 42% for ustekinumab and 40% for vedolizumab. One patient treated with ustekinumab and two with vedolizumab underwent a new intestinal resection.; CONCLUSIONS: Ustekinumab and vedolizumab seem to be effective in the prevention of POR in patients at high risk. Our results warrant controlled trials comparing these drugs with conventional therapies. Copyright © 2022. Published by Elsevier Ltd.

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).

Background and Aims Patient-reported outcome measures [PROMs] aim to measure patients’ perception of how their disorder influences everyday functioning. The objective of this study was to develop a PROM to assess disease activity in microscopic colitis [MC] fulfilling the requirements of the Food and Drug Administration [FDA]. Methods The European Microscopic Colitis Activity Index [E-MCAI] was developed in four steps. [1] A list of symptoms associated with active MC was created by a group of experts in the field. [2] Content validity of the symptoms was performed by experts [n = 14] and patients [n = 79] using the Content Validity Index. [3] Questions and response alternatives were created for each symptom, and validity of the E-MCAI was evaluated with cognitive interviews with patients [n = 7] and by the experts. [4] A pilot postal survey was performed to ensure usability. Results Seven of the symptoms related to active MC fulfilled the criteria for content validity and were included in the E-MCAI: stool consistency, stool frequency, stools at night, feel a need to pass more stools shortly after a bowel movement, urgent need to empty the bowel, leakage of stool and abdominal pain. The development and validation process resulted in the current version of the E-MCAI consisting of six questions related to MC. Conclusions The E-MCAI was developed using the methods advocated by the FDA. The evaluation indicates good content validity. Further evaluation will be performed to achieve construct validity, reliability and responsiveness in future cross-sectional and longitudinal studies.

Introducción: Diferentes vacunas frente a SARS-CoV-2 están actualmente en el mercado y se recomiendan en pacientes con Enfermedad Inflamatoria Intestinal (EII). No tenemos suficiente evidencia sobre la aceptación de este tipo de vacunas. El objetivo del estudio fue evaluar la aceptación de la vacuna frente a SARS-CoV-2 por parte de gastroenterólogos y pacientes con EII. Métodos: Se realizó una encuesta online a 8000 pacientes de ACCU-España y 1000 miembros de GETECCU. Se enviaron tres invitaciones entre Octubre-Diciembre 2020. Se realizó un análisis descriptivo, comparando las respuestas de médicos y pacientes. Resultados: 144 gastroenterólogos [63% mujeres, edad media 43 años (DE 9,5)], y1302 pacientes [72% mujeres, edad media 43 años (DE 12)] respondieron a la encuesta. 95% de los médicos recomendaban la vacuna frente a SARS-CoV-2 en pacientes con EII, 87% consideraron que su estrategia de vacunación frente a diferentes vacunas no había cambiado tras la pandemia frente al 12% que consideraban que actualmente remitían más pacientes a vacunación. En cuanto a los pacientes con EII, sólo 43% aceptaban la vacunación frente a SARS-CoV-2, frente a 43% que no estaban seguros. El sexo masculino (p

Background Whereas the exact aetiology of microscopic colitis [MC] remains unknown, a dysregulated immune response to luminal factors or medications is the most accepted pathogenesis hypothesis. Methods We conducted a systematic review of the pathogenesis of MC. We applied the Joanna Briggs Institute methodologies and the PRISMA statement for the reporting of systematic reviews [PROSPERO Trial Identifier: CRD42020145008]. Populations, Exposure of interest, and Outcome [PEO] questions were used to explore the following topics in MC: 1] intestinal luminal factors; 2] autoimmunity; 3] innate immunity; 4] adaptive immunity; 5] extracellular matrix; 6] genetic risk factors; and 7] mechanism of diarrhoea. A search was done in PubMed, Embase, and Web of Science up to February 2020. A narrative description was performed explaining the findings for each aspect of MC aetiopathogenesis. Results Thirty-eight documents provided evidence for PEO1, 100 for PEO2, 72 for PEO3 and 4, 38 for PEO5, 20 for PEO6, and 23 for PEO7. The majority of documents were cohorts, case reports, and case series, with a few case-control and some experimental studies. Consistency among data provided by different studies was considered to support pathogenetic hypotheses. MC is a multifactorial disease believed to involve innate and adaptive immune responses to luminal factors, genetic risk, autoimmunity, and extracellular matrix alterations, all contributing by varied mechanisms to watery diarrhoea. Conclusions This is the first systematic review on the aetiology of MC supporting the notion that MC is a multifactorial disease. However, high-profile studies are lacking, and most evidence derives from small heterogeneous studies.

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.

INTRODUCTION : The introduction and broad use of new immunosuppressive agents, including biologic agents and JAK inhibitors, have revolutionised treatment of inflammatory bowel disease [IBD] in recent decades. With such immunosuppression, the potential for opportunistic infection is a key safety concern. [...]

Background: One of the most valued targets in inflammatory bowel disease (IBD) is for physicians to provide and patients to receive a high-level quality of care. This study aimed to evaluate the implementation of a nationwide quality certification programme for IBD units. Methods: Identification of quality indicators (QI) for IBD Unit certification was based on Delphi methodology that selected 53 QI, which were subjected to a normalisation process. Selected QI were then used in the certification process. Coordinated by GETECCU, this process began with a consulting round and an audit drill followed by a formal audit carried out by an independent certifying agency. This audit involved the scrutiny of the selected QI in medical records. If 80%–90% compliance was achieved, the IBD unit audited received the qualification of “advanced”, and if it exceeded 90% the rating was “excellence”. Afterwards, an anonymous survey was conducted among certified units to assess satisfaction with the programme for IBD units. Results: As of January 2021, 66 IBD units adhere to the nationwide certification programme. Among the 53 units already audited by January 2021, 31 achieved the certification of excellence, 20 the advanced certification, and two did not obtain the certification. The main survey results indicated high satisfaction with an average score of 8.5 out of 10. Conclusion: Certification of inflammatory bowel disease units by GETECCU is the largest nationwide certification programme for IBD units reported. More than 90% of IBD units adhered to the programme achieved the certification, AbbVie sponsored the CUE programme. AbbVie had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Small bowel capsule endoscopy (SBCE) is a non-invasive diagnostic technique whose use in inflammatory bowel disease (IBD) has spread. A panenteric capsule, PillCam Crohn's (PCC), has recently been developed. We lack information on the availability and use of the CEID and PCC in our environment.We conducted an electronic and anonymous survey among the members of the Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa (GETECCU) [Spanish Working Group on Crohn's Disease and Ulcerative Colitis] and the Asociación Española de Gastroenterología (AEG) [Spanish Association of Gastroenterology], consisting of 37 multiple-choice questions.One hundred and fifty members participated, the majority dedicated to IBD (69.3%). 72.8% worked at centres with an IBD unit. 79% had SBCE available at their hospital, 14% referred patients to another centre; 22% had a PCC available, 9% referred patients to another centre. 79.3% of respondents with available SBCE used it in a small percentage of patients with IBD and 15.6% in the majority. The most frequent scenarios were suspicion of Crohn's disease (76.3%), assessment of inflammatory activity (54.7%) and assessment of the extent of the disease (54.7%). More than half (59.7%) preferentially used the Patency capsule to assess intestinal patency. Almost all respondents (99.3%) considered that training resources should be implemented in this technique.SBCE is widely available in Spanish hospitals for the management of IBD, although its use is still limited. There is an opportunity to increase training in this technique, and consequently its use.

Background The outbreak of COVID-19 has rapidly evolved into a pandemic that has represented a challenge to health systems worldwide. Inflammatory bowel disease (IBD) units have been forced to change their practices to address the disease and to ensure the quality of care. Methods We conducted a national survey among IBD gastroenterologist members of the Spanish Working Group on Crohn’s Disease and Colitis regarding changes of practice, IBD treatments, and diagnosis and treatment of COVID-19. Results We received 54 answers from Spanish hospitals. One hundred percent of the IBD units rescheduled onsite visits to telematic consultation, and elective endoscopic and surgical procedures were delayed. Protective measures were also taken in the infusion units (100% of health centers) and hospital pharmacies, with 40.7% sending subcutaneous medications to patients. No switching between intravenous and subcutaneous anti-tumor necrosis factor drugs were made. We also found that 96.1% of IBD units advised their patients to maintain treatment if they were asymptomatic for COVID-19. For patients with COVID-19 symptoms, 92.6% of IBD units referred them to primary care or the emergency department. In addition, 7.5% of IBD units made a COVID-19 diagnosis through polymerase chain reaction and/or chest x-ray. Modifications in IBD treatment and treatment recommended for COVID-19 are also discussed. Conclusions We report a representative national survey of changes made in the structure, diagnosis of COVID-19, and modifications in IBD treatments within IBD units.

Inflammatory bowel disease is a chronic and progressive disorder of the gastrointestinal tract. A relevant proportion of patients develop complicated lesions, defined as strictures, fistulas and/or abscesses already at diagnosis, and this proportion increases over time. The preclinical phase defines the period of time from the appearance of the first immune disturbances until the development of overt disease, and it may be present months to years before the diagnosis. Multiple biomarkers (e.g., C-reactive protein, interleukin-6, fecal calprotectin) and cellular mechanisms (e.g., complement cascade, lysosomes, innate immunity, and glycosaminoglycan metabolism) are already altered during this period. Research in this area allows the description of the initial immune disturbances that may identify potential targets and lead to the development of new drug therapies. During this period, different interventions in high-risk individuals, including drugs or environmental factors, will open the possibility of innovative strategies focused on the reduction of complications, or even prevention trials for inflammatory bowel disease. Here, we review the most relevant findings regarding the characteristics, prevalence and biomarkers associated with preclinical disease, along with their possible use in our future clinical practice.

Introduction Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, non-bloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder. Methods Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method. Results These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice. Conclusion These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis. Funding Agencies|UEG Activity Grant

Patients with ulcerative colitis (UC) have an increased risk of colorectal cancer. Scarce data regarding the development of adenomas in these patients are available both for normal and colitic mucosa.The objective of this article is to evaluate the prevalence of adenomatous polyps and associated risk factors in patients with UC.Patients with UC were identified from the databases of two tertiary referral centers. Medical, endoscopic and histologic reports were reviewed.A total of 403 patients were included (53% male; 33% extensive colitis) and 1065 colonoscopies (median per patient, 2) were recorded and analyzed. Seventy-four adenomas in 47 patients (11.7%) and three cases of colorectal cancer were found during a median follow-up of 6.3 years. The cumulative risk of colorectal adenoma was 4.7%, 16.7%, 23.6% and 34.4% at 10, 20, 30 and 40 years from UC diagnosis, respectively. The cumulative risk of developing metachronous colorectal adenoma was 66.7%, 87.9%, and 90.9% at 5, 10, and 15 years from first adenoma detection. Older age at UC diagnosis and longer disease duration were independent risk factors for colorectal adenoma development.The prevalence of colorectal adenomas among UC patients seems to be higher than previously reported, although lower than in the background population.

Resumen Objetivos Establecer recomendaciones para el manejo de los aspectos psicologicos de los pacientes con enfermedad inflamatoria intestinal (EII). Metodos Se llevo a cabo una reunion con un grupo de expertos en EII formado por medicos, psicologos, enfermeras y representantes de pacientes. Se presentaron resultados de: 1) un grupo focal previo, 2) encuestas a medicos y pacientes y 3) una revision sistematica sobre instrumentos de cribado de ansiedad y depresion. Se realizo una discusion guiada sobre los aspectos psicologicos y emocionales mas importantes en EII, los criterios de derivacion apropiados y situaciones a evitar. Se selecciono el instrumento validado mas aplicable a la practica clinica. Se diseno un documento con recomendaciones, asi como una encuesta Delphi. La encuesta fue enviada al grupo y a un comite cientifico seleccionado del grupo GETECCU, con el objetivo de establecer el grado de apoyo a las recomendaciones establecidas. Resultados Se establecieron 15 recomendaciones, pertenecientes a 3 procesos clave: 1) que pasos dar para identificar problemas psicologicos en consulta de EII, 2) criterios de derivacion a profesionales de la salud mental y 3) abordaje de los problemas psicologicos. Conclusiones Se deben facilitar recursos a los profesionales sanitarios para que puedan tratar estos aspectos en consulta, identificar los trastornos que puedan afectar el curso de la enfermedad o su impacto en la vida del paciente, para ser tratados y seguidos por el profesional mas adecuado. Estas recomendaciones pueden servir de base para el rediseno de los servicios o procesos de EII y como justificacion para la formacion del personal sanitario.

Background: Onset during old age has been reported in upto 10% of total cases of inflammatory bowel disease (IBD). Aim: To evaluate phenotypic characteristics and the use of therapeutic resources in patients with elderly onset IBD. Methods: Case-control study including all those patients diagnosed with IBD over the age of 60 years since 2000 who were followed-up for >12 months, identified from the IBD databases. Elderly onset cases were compared with IBD patients aged 18 to 40 years at diagnosis, matched by year of diagnosis, gender and type of IBD (adult-onset). Results: One thousand three hundred and seventy-four elderly onset and 1374 adult-onset cases were included (62% ulcerative colitis (UC), 38% Crohn's disease (CD)). Among UC patients, elderly onset cases had a lower proportion of extensive disease (33% vs 39%; P < 0.0001). In CD, elderly onset cases showed an increased rate of stenosing pattern (24% vs 13%; P < 0.0001) and exclusive colonic location (28% vs 16%; P < 0.0001), whereas penetrating pattern (12% vs 19%; P < 0.0001) was significantly less frequent. Regarding the use of therapeutic resources, there was a significantly lower use of corticosteroids (P < 0.0001), immunosuppressants (P < 0.0001) and anti-TNFs agents (P < 0.0001) in elderly onset cases. Regarding surgery, we found a significantly higher surgery rate among elderly onset UC cases (8.3% vs 5.1%; P < 0.009). Finally, elderly onset cases were characterised by a higher rate of hospitalisations (66% vs 49%; P < 0.0001) and neoplasms (14% vs 0.5%; P < 0.0001). Conclusions: Elderly onset IBD shows specific characteristics and they are managed differently, with a lower use of immunosuppressants and a higher rate of surgery in UC.

Resumen Colitis microscopica es un termino generico que incluye 2 formas principales, colitis colagena y colitis linfocitica, que describe una forma de enfermedad inflamatoria intestinal con curso cronico y recidivante. La incidencia de colitis microscopica es entre 2 y 8 veces mas alta en mujeres que en hombres; sin embargo, la edad contribuye mas que el sexo en el riesgo de colitis colagena (OR 8,3 para edad ≥ 65 vs.

Background Vδ1+ and Vδ2+ are TCRγδ lymphocytes of the gut intraepithelial compartment that recognise proteins without help of antigen-presenting cells. Its relevance in inflammatory bowel disease (IBD) is unknown. Aim To measure Vδ1+ and Vδ2+ in T-cell subtypes [CD4+, CD8+, double positive (DP,CD4+CD8+), double negative (DN,CD4−CD8−) and CD103+] of healthy and IBD inflammed gut mucosa. Methods Twenty-six active IBD patients without immunosuppressants (n = 18 Crohn’s disease (CD), eight ulcerative colitis (UC)) and 10 healthy controls (paired biopsies of ileum, right and left colon) were included. Lymphocytes were analysed with LSRFortessa cytometer. Results expressed as % median (25–75%IQI). Results Healthy mucosa: reduction in ileum of total CD3+Vδ1+ due to CD3+CD8+Vδ1+ and CD3+DN_Vδ1+ Conclusion Reduction of Vδ1+ and Vδ2+, mainly of CD103+, may play a role in IBD pathophysiology by perpetuating inflammation. Increase of CD3+Vδ1+CD4+ in both Ileal CD and UC may compensate this decrease with a selective increase in ‘helper’ function.

In this issue of the Young GI Angle, we have the opportunity to share the personal experience of four experienced clinicians with a successful career in different fields of gastroenterology. Here, you will find some of their most important decisions that have been a crucial turning point in their life. Many young fellows will face similar situations. Therefore, the testimony of these authors may help those taking difficult decisions during their professional career.

Background &amp, Aims: Determining whether patients with lymphocytic enteritis (LE) have coeliac disease is a challenge. We analysed the variables associated with a low-grade coeliac enteropathy diagnosis in patients with suspected coeliac disease but without villous atrophy, and developed a scoring system to identify them. Methods: We collected data from 2010 through to 2016 on patients with lymphocytic enteritis and persistent symptoms compatible with the clinical spectrum of coeliac disease. One hundred and four patients starting on a gluten-free diet (GFD) were included. Duodenal biopsies were collected before the GFD and analysed for numbers of CD3+ T-cell receptor gamma delta+ (TCR&gamma, &delta, +), and CD3&minus, intraepithelial lymphocytes. We performed a logistic regression analysis to identify factors associated with a low-grade coeliac enteropathy diagnosis. Results: Sixty-two patients achieved clinical remission after the GFD. Fifty of these 62 patients were diagnosed with low-grade coeliac enteropathy. Multivariate analysis identified the presence of &gt, 25% intraepithelial lymphocytosis, HLA-DQ2.5, positive serology, and increased numbers of TCR&gamma, + cells with a low-grade coeliac enteropathy diagnosis. We developed a scoring system that identified patients with an area under the ROC curve (AUC) of 0.91. Scores of &gt, 10 had 86% sensitivity and 85% specificity. Conclusion: We developed a scoring system that identifies patients likely to be diagnosed with low-grade coeliac enteropathy with an AUC value of 0.91.

BACKGROUND Thiopurines are the most widely used immunosuppressants in IBD although drug-related adverse events (AE) occur in 20%-30% of cases. AIM To evaluate the safety of thiopurines in elderly IBD patients METHODS: Cohort study including all adult patients in the ENEIDA registry who received thiopurines. Patients were grouped in terms of age at the beginning of thiopurine treatment, specifically in those who started thiopurines over 60 years or between 18 and 50 years of age. Thiopurine-related AEs registered in the ENEIDA database were compared. RESULTS Out of 48 752 patients, 1888 started thiopurines when over 60 years of age and 15 477 under 50 years of age. Median treatment duration was significantly shorter for those who started thiopurines >60 years (13 [IQR 2-55] vs 32 [IQR 5-82] months; P 60 years had higher rates of all types of myelotoxicity, digestive intolerance and hepatotoxicity. Thiopurines were discontinued due to AEs (excluding malignancies and infections) in more patients starting >60 years (67.2% vs 63.1%; P

Background and Aims There is controversy as to whether the risk of relevant infection in IBD is related to immunosuppressants or the disease itself. The aims of this study were to evaluate: [1] the life-long prevalence and types of relevant infections in patients with IBD related to immunosuppressive treatment, and [2] the relationship of both infection and patient comorbidity to mortality. Methods Observational multicentre retrospective study of IBD patients that presented a relevant infection. For each case, four periods of infection exposure were analysed: P1: pre-IBD diagnosis, P2: from IBD diagnosis to immunosuppressant initiation, P3: during immunosuppressant therapy, and P4: after treatment withdrawal. Results The life-long prevalence of relevant infection in the total cohort of patients [6914] was 3%, and 5% in immunosuppressed patients [4202]. 366 relevant infections were found in 212 patients [P1: 9, P2: 17, P3: 334, and P4: 6]. Differences between periods were significant [p < 0.0001]. The most frequent types of infection were respiratory, intestinal and urinary. The most frequent opportunistic infections were tuberculosis [prevalence: 2.6/1000] and herpes zoster [prevalence: 3.9/1000]. Herpes zoster infection was associated with thiopurines alone or in combination with anti-TNF in 75% of the cases, whereas tuberculosis was associated with anti-TNF in 94% of patients. The overall mortality was 4.2%. Infection-related mortality was 2.8% and it was not influenced by comorbidity. Conclusions Relevant infections in IBD patients are rare and appear to be related to immunosuppression. Relevant infection is a major cause of death in IBD.

Introduction: The study of intraepithelial lymphocytes (IEL) by flow cytometry is a useful tool in the diagnosis of coeliac disease (CD). Previous data showed that an increase in %TCRγδ+ and decrease of %CD3− IEL constitute a typical CD cytometric pattern with a specificity of 100%. However, there are no data regarding whether there are differences in the %TCRγδ+ related to sex, age, titers of serology, and degree of histological lesion. Study aims: To confirm the high diagnostic accuracy of the coeliac cytometric patterns. To determine if there are differences between sex, age, serology titers, and histological lesion grade. Results: We selected all patients who fulfilled “4 of 5” rule for CD diagnosis (n = 169). There were no differences in %TCRγδ+ between sexes (p = 0.909), age groups (p = 0.986), serology titers (p = 0.53) and histological lesion grades (p = 0.41). The diagnostic accuracy of complete CD cytometric pattern was: specificity 100%, sensitivity 82%, PPV 100%, NPV 47%. Conclusion: We confirmed, in a validation cohort, the high diagnostic accuracy of complete CD pattern irrespective of sex, age, serology titers, and grade of mucosal lesion.

Background and Aims: There is very limited information regarding region-specific immunological response in human intestine. We aimed to determine differences in immune compartmentalisation between ileum and colon in healthy and inflamed mucosa. Methods: T cell profile and its apoptosis were measured by flow cytometry, Th1, Th17, Treg [CD4+CD25+FOXP3+], double positive [DP, CD3+CD4+CD8+] and double negative T cells [DN, CD3+CD4-CD8-], immunohistochemistry \[FOXP3, caspase-3], and real-time polymerase chain reaction [PCR\] \[IFN-γ, IL-17-A, and FOXP3\] on biopsies from different regions of healthy intestine and of intestine in inflammatory bowel diseases. Results: Healthy colon showed higher percentages of Treg, Th17, and DN, and lower numbers of DP T cells compared with ileum [ p < 0.05]. Some but not all region-specific differences were lost in inflammatory conditions. Disease-specific patterns were found: a Th1/Th17 pattern and a Th17 pattern in Crohn’s disease and ulcerative colitis respectively, whereas a reduction in Th1/Th17 was found in microscopic colitis. In colonic Crohn’s disease and microscopic colitis, DN T cells had a pattern inverse to that of Th1/Th17 (increase in microscopic colitis [ p < 0.05] and decrease in Crohn’s disease [ p < 0.005]). Higher levels of lymphocyte apoptosis were found in healthy colon compared with the ileal counterparts [ p = 0.001]. All forms of colonic inflammation presented a dramatic decrease in apoptosis compared with healthy colon. By contrast ileal Crohn’s disease showed higher levels of cleaved-Caspase+ CD3+ cells. Conclusions: Immunological differences exist in healthy gastrointestinal tract. Inflammatory processes overwhelm some location-specific differences, whereas others are maintained. Care has to be taken when analysing immune response in intestinal inflammation, as location-specific differences may be relevant.

Background: Lymphocytic (LC) and collagenous (CC) colitis are the two major forms of microscopic colitis (MC). The aim of this study was to identify similarities and differences in their mucosal immune characteristics. Methods: Colonic biopsies from 15 CC, 8 LC, and 10 healthy controls were collected. Mucosal lymphocytes were assessed by flow cytometry. Tissue gene expression and protein levels were determined by real-time PCR and ELISA, respectively. Results: LC patients had lower numbers of CD4+ and double-positive CD4+CD8+mucosal T lymphocytes, and higher numbers of CD8+ and CD4+TCRγδ+ mucosal T cells, compared with controls and CC patients. Regulatory Treg (CD4+CD25+FOXP3+) and double-negative (CD3+CD4-CD8-) T cell percentages were higher in both CC and LC compared with controls, coupled with higher levels of the anti-inflammatory IL-10, both at mRNA and protein levels. By contrast, Th1 and Th17 cells were lower in both CC and LC, although gene expression of Th1/Th17 cytokines was higher in both. Conclusion: CC and LC share some regulatory and effector mechanisms, but not others. Higher IL-10 levels and higher Treg and double-negative T cell percentages, found in both CC and LC, could be responsible for the lack of progression of structural damage and the blockade of proinflammatory cytokine production. However, CC and LC are revealed as separate, independent entities, as they show clearly different mucosal lymphocyte profiles, which could be caused by different luminal triggers of the two diseases. Hence, CC and LC are two closely related but independent intestinal disorders.

Aims: (1) Assess the population-based incidence of severe olmesartan-associated enteropathy. (2) To describe patients of the Spanish registry. (3) Evaluate markers of potential coeliac disease and associated autoimmunity. Methods: Crude incidence rates in the area of Terrassa (Catalonia) were calculated. Clinical characteristics of patients in the Spanish registry were collected. Duodenal lymphocyte subpopulations and anti-TG2 IgA deposits were assessed in a subset of patients. Results: Annual incidence rates (2011-2014) ranged from 0 to 22 cases per 104 treated patients. Twenty patients were included in the Spanish registry. Nineteen (95%) exhibited villous atrophy and 16 (80%) had severe enteropathy. Lupus-like disease occurred during olmesartan treatment in 3 patients. HLA-DQ2/DQ8 was positive in 64%. Markers of potential coeliac disease were present in 4 out of 8 patients (positive anti-TG2 deposits and/or increased CD3+ gammadelta+ intraepithelial lymphocytes and reduced CD3-). Histopathological changes and clinical manifestations including autoimmune disorders improved after olmesartan discontinuation but not after gluten-free diet, irrespective of the presence or absence of coeliac markers. Conclusions: Incidence of severe olmesartan-associated enteropathy was low. Autoimmune phenomena were present in a subset of cases and reversed after olmesartan removal. A genetic coeliac disease background and the presence of potential coeliac markers might uncover predisposing factors. (C) 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Background CD161 is a type C lectin expressed in NKs cells and peripheral T cells (TCRγδ and αβ, NKTs), enriched in intestinal populations. Its expression can be modulated by infections and inflammation. MAIT cells are a subset of innate antimicrobial T-cells abundant in the mucosa but their role in immunological regulation is still unknown. Aim To measure CD161 levels in subtypes of T-lymphocytes of intestinal mucosa: CD4+, CD8+, double positive (DP,CD4+CD8+), double negative (DN,CD4−CD8−), MAIT cells (CD161+TCRVα7.2+) and intraepithelial cells (CD103+) Methods Twenty-six patients with active inflammatory bowel disease (IBD) without immunosuppressive treatment (n = 9 Crohn’s disease -CD- colon, 9 CD ileum, n = 8 ulcerative colitis -UC- and 10 healthy controls (paired biopsies of ileum, right and left colon) were included. Lymphocyte subpopulations were analysed with LSRFortessa cytometer. Non-parametric Kruskal–Wallis test was applied. Results are expressed as % of median (25–75%IQI). Results In healthy mucosa, we did not find differences related to location in any of CD161 subpopulations except for increase of CD3+CD161+CD103+ and decrease of CD3+CD161+CD103− in left colon compared with right colon and ileum. Regarding MAIT cells, a progressive decrease was observed in distal parts of intestine for CD3+MAIT+CD103+ while CD3+MAIT+CD103− subpopulation has a specular behaviour; CD3+CD8+MAIT+ was increased in ileum compared with colon (Table 1). Conclusion There is a regional specialisation for the subset CD103+ of both CD161+CD103+ and MAIT_CD103+ cells in healthy intestine. CD3+CD161+ T cells are reduced in IBD colonic inflammation and could serve as a marker of active IBD but not to sort between CD and UC.

Background and Aim Thiopurines prevent Crohn's disease (CD) endoscopic recurrence (ER) at least in 50% of patients 1 year after surgery. This study aimed to evaluate the value of adding mesalazine in patients with subclinical ER despite preventive thiopurine therapy. Methods Crohn's disease patients with ileocecal resection treated with thiopurines for postsurgical recurrence prevention in whom mesalazine was added (cases) to treat ER without clinical recurrence (CR) were identified and compared with those in whom no treatment was added to thiopurines (controls). All patients were followed up for at least 1 year from the index endoscopy. Development of CR as well as evolution of mucosal lesions was evaluated. Results Thirty-seven patients were included (19 cases and 18 controls). Initial Rutgeerts' score was i2 in 16 patients (9 cases and 7 controls), and i3 in 21 patients (10 cases and 11 controls). After a median clinical follow-up of 59 months (interquartile range 22–100) from the index endoscopy, six cases (32%) and two controls (11%) developed CR (P = 0.2). After a median time to last endoscopic follow-up of 23 months (interquartile range 17–71), 18 patients (49%) showed improvement in Rutgeerts' score, 11 patients (30%) demonstrated progression of mucosal lesions, and 8 (22%) had no changes, with no differences between study groups. Conclusions The addition of mesalazine seems to be of no benefit in patients with subclinical endoscopic recurrence while on thiopurine prevention. Moderate endoscopic postsurgical recurrence while on thiopurines may even revert with no additional therapy in some patients.

Background: Active smoking has been associated with a higher risk of developing Crohn's disease (CD). However, its impact on clinical outcomes has been controversial among studies. Aims: To evaluate the influence of active smoking on initial manifestations of CD, the development of disease-related complications, and therapeutic requirements. Methods: Patients diagnosed with CD within a ten-year period (1994-2003) were identified. Clinical and therapeutic features until October 2008 or loss of follow-up were recorded. Smoking status was assessed at each major disease-related event (e.g. penetrating and stricturing complications, perianal disease, intestinal resection, introduction of immunomodulators or biological agents). Results: A total of 259 patients were included in the study with a median follow-up period of 91 months. At diagnosis, 50.5% were active smokers and only 12% of them quit smoking during follow-up, mostly after a major disease-related event occurred. Smoking at diagnosis was not associated with a particular CD presentation. Active smoking did not influence the development of strictures, intraabdominal and perianal penetrating complications, or increased resectional surgery, biological therapy or immunomodulators requirements. Conclusions: Patients who develop CD while smoking seem to have a similar disease course to those who never smoked. (c) 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.