Genetic biomarkers of methotrexate response and safety in Crohn's disease: Data from the Spanish ENEIDA registry.

AIMS: Methotrexate (MTX) is used to induce and maintain remission in patients with steroid-dependent Crohn's disease (CD). Despite its proven efficacy, its use is limited due to associated adverse events. Polymorphisms involving folate pathway genes might influence MTX efficacy and toxicity. We aimed to assess the impact of certain polymorphisms on the therapeutic outcomes of MTX in CD. METHODS: Patients with CD who exclusively followed MTX monotherapy and fulfilled inclusion criteria were identified from the GETECCU ENEIDA registry. Variants of ATIC, DHFR, MTHFR, SLC19A1, ABCB1 and ABCC3 genes were analysed and their association with efficacy and toxicity was assessed. RESULTS: A total of 129 patients were included in the analysis. MTX was used at a median weekly dose of 25 mg (interquartile range, 15-25 mg) and a median time of 14 months (interquartile range, 4-52 months). Thirty-seven percent of the patients achieved disease remission with MTX monotherapy, while 34% were nonresponders (MTX failure). MTX-related toxicity occurred in 40 patients (30%), leading to MTX discontinuation in 19%. DHFR rs408626 (odds ratio [OR] 3.12, 95% confidence interval [CI] 1.22-7.69; P = .017) and MTHFR rs1801133 (OR 2.86, 95% CI 1.23-6.68; P = .015) variants, and smoking (OR 2.61, 95% CI 1.12-6.05; P = .026) were associated with a higher risk of MTX failure. Additionally, the MTHFR rs1801131 variant was associated with a higher risk of MTX-related adverse effects (OR 2.78, 95% CI 1.26-6.13, P = .011). CONCLUSION: Our study shows that variants of MTHFR and DHFR genes may be associated with MTX efficacy and adverse events in patients with CD.

Initial management of intraabdominal abscesses and preventive strategies for abscess recurrence in penetrating Crohn's disease: a national multicenter study based on ENEIDA registry.

INTRODUCTION: Intra-abdominal abscesses complicating Crohn's disease (CD) are a challenging situation. Their management, during the hospitalization and after resolution, is still unclear. METHODS: Adult patients with CD complicated with intraabdominal abscess who required hospitalization were included from the prospectively maintained ENEIDA registry from GETECCU. Initial strategy effectiveness and safety to resolve abscess was assessed. Survival analysis was performed to evaluate recurrence risk. Predictive factors associated with resolution were evaluated by multivariate regression and predictive factors associated with recurrence were assessed by Cox regression. RESULTS: 520 patients from 37 Spanish hospitals were included; 322 (63%) were initially treated with antibiotics alone, 128 (26%) with percutaneous drainage, and 54 (17%) with surgical drainage. The size of the abscess was critical to the effectiveness of each treatment. In abscesses < 30mm, the antibiotic was as effective as percutaneous or surgical drainage. However, in larger abscesses, percutaneous or surgical drainage was superior. In abscesses > 50mm, surgery was superior to percutaneous drainage, although it was associated with a higher complication rate. After abscess resolution, luminal resection was associated with a lower 1-year abscess recurrence risk (HR 0.43, 95% CI 0.24-0.76). However, those patients who initiated anti-TNF therapy had a similar recurrence risk whether luminal resection had been performed. CONCLUSIONS: Small abscesses (<30mm) can be managed with antibiotics alone, while larger ones require drainage. Percutaneous drainage will be effective and safer than surgery in many cases. After discharge, anti-TNF therapy reduces abscess recurrence risk in a similar way to bowel resection.

C4BP(ß-)-mediated immunomodulation attenuates inflammation in DSS-induced murine colitis and in myeloid cells from IBD patients.

The most recent and promising therapeutic strategies for inflammatory bowel disease (IBD) have engaged biologics targeting single effector components involved in major steps of the immune-inflammatory processes, such as tumor necrosis factor, interleukins or integrins. Nevertheless, these molecules have not yet met expectations regarding efficacy and safety, resulting in a significant percentage of refractory or relapsing patients. Thus, novel treatment options are urgently needed. The minor isoform of the complement inhibitor C4b-binding protein, C4BP(ß-), has been shown to confer a robust anti-inflammatory and immunomodulatory phenotype over inflammatory myeloid cells. Here we show that C4BP(ß-)-mediated immunomodulation can significantly attenuate the histopathological traits and preserve the intestinal epithelial integrity in dextran sulfate sodium (DSS)-induced murine colitis. C4BP(ß-) downregulated inflammatory transcripts, notably those related to neutrophil activity, mitigated circulating inflammatory effector cytokines and chemokines such as CXCL13, key in generating ectopic lymphoid structures, and, overall, prevented inflammatory immune cell infiltration in the colon of colitic mice. PRP6-HO7, a recombinant curtailed analogue with only immunomodulatory activity, achieved a similar outcome as C4BP(ß-), indicating that the therapeutic effect is not due to the complement inhibitory activity. Furthermore, both C4BP(ß-) and PRP6-HO7 significantly reduced, with comparable efficacy, the intrinsic and TLR-induced inflammatory markers in myeloid cells from both ulcerative colitis and Crohn's disease patients, regardless of their medication. Thus, the pleiotropic anti-inflammatory and immunomodulatory activity of PRP6-HO7, able to "reprogram" myeloid cells from the complex inflammatory bowel environment and to restore immune homeostasis, might constitute a promising therapeutic option for IBD.

Endoscopic treatment (endoscopic balloon dilation/self-expandable metal stent) vs surgical resection for the treatment of de novo stenosis in Crohn's disease (ENDOCIR study): an open-label, multicentre, randomized trial.

BACKGROUND: Stenosis is one of the most common complications in patients with Crohn's disease (CD). Endoscopic balloon dilation (EBD) is the treatment of choice for a short stenosis adjacent to the anastomosis from previous surgery. Self-expandable metal stents (SEMS) may be a suitable treatment option for longer stenoses. To date, however, there is no scientific evidence as to whether endoscopic (EBD/SEMS) or surgical treatment is the best approach for de novo or primary stenoses that are less than 10 cm in length. METHODS/DESIGN: Exploratory study as "proof-of-concept", multicentre, open-label, randomized trial of the treatment of de novo stenosis in the CD; endoscopic treatment (EBD/SEMS) vs surgical resection (SR). The type of endoscopic treatment will initially be with EDB; if a therapeutic failure occurs, then a SEMS will be placed. We estimate 2 years of recruitment and 1 year of follow-up for the assessment of quality of life, costs, complications, and clinical recurrence. After the end of the study, patients will be followed up for 3 years to re-evaluate the variables over the long term. Forty patients with de novo stenosis in CD will be recruited from 15 hospitals in Spain and will be randomly assigned to the endoscopic or surgical treatment groups. The primary aim will be the evaluation of the patient quality of life at 1 year follow-up (% of patients with an increase of 30 points in the 32-item Inflammatory Bowel Disease Questionnaire (IBDQ-32). The secondary aim will be evaluation of the clinical recurrence rate, complications, and costs of both treatments at 1-year follow-up. DISCUSSION: The ENDOCIR trial has been designed to determine whether an endoscopic or surgical approach is therapeutically superior in the treatment of de novo stenosis in CD. TRIAL REGISTRATION: ClinicalTrials.gov NCT04330846. Registered on 1 April 1 2020. https://clinicaltrials.gov/ct2/home.

Clinical and endoscopic outcomes of patients with colonic Crohn's disease treated with 5-aminosalicylates as monotherapy / Resultados clínicos y endoscópicos de pacientes con enfermedad de Crohn colónica tratados con 5-aminosalicilatos como monoterapia

Background: In spite of the lack of evidence regarding the clinical benefits of oral 5-aminosalicylic acid (5-ASA) compounds in Crohn's disease (CD), these drugs are frequently used in daily clinical practice, particularly for colonic CD. Our aim is to assess the use and clinical outcomes of 5-ASA of those patients with colonic CD treated with 5-ASA as monotherapy. Methods: Patients diagnosed with isolated colonic CD and treated with 5-ASA but never exposed to immunosuppressants or biologicals were identified from the local databases of five referral centres. A retrospective review of clinical and endoscopic outcomes was performed. Results: Out of 545 patients with isolated colonic CD, 106 (19%) were treated with oral 5-ASA in monotherapy as maintenance therapy. The median follow-up was 144 months (interquartile range [IQR], 48–234). Almost all of the patients (92%) presented an inflammatory pattern and 11% developed perianal disease. Half of the patients had already received 5-ASA at diagnosis, and the median duration of 5-ASA treatment was 107 months (IQR 22.5–187). Endoscopic remission, as defined by the absence of ulcers at the last complete colonoscopy, was observed in 65% of those patients undergoing at least one colonoscopy during follow-up. Male gender and extraintestinal manifestations were associated with a lower likelihood of achieving endoscopic remission. Nine patients required colectomy, but mostly soon after CD diagnosis. Conclusions: 5-ASA seems to be of benefit in the long-term in one fifth of patients with colonic CD as the only maintenance therapy and should be considered in fragile patients with Crohn's colitis.(AU)

Antecedentes: A pesar de la falta de evidencia sobre los beneficios clínicos de los 5-aminosalicíilatos (5-ASA) orales en la enfermedad de Crohn (EC), estos medicamentos se utilizan con frecuencia en la práctica clínica diaria, particularmente para la EC cólica. Nuestro objetivo es evaluar el uso y los resultados clínicos del 5-ASA en aquellos pacientes con EC cólica tratados con 5-ASA en monoterapia. Métodos: Los pacientes diagnosticados con EC cólica aislada y tratados con 5-ASA pero nunca expuestos a inmunosupresores o agentes biológicos fueron identificados a partir de las bases de datos locales de 5 centros de referencia. Se realizó una revisión retrospectiva de los resultados clínicos y endoscópicos. Resultados: De 545 pacientes con EC cólica aislada, 106 (19%) fueron tratados con 5-ASA oral en monoterapia como terapia de mantenimiento. La mediana de seguimiento fue de 144 meses (rango intercuartílico: 48-234). Casi todos los pacientes (92%) presentaban un patrón inflamatorio y un 11% desarrollaron enfermedad perianal. La mitad de los pacientes ya habían recibido 5-ASA en el momento del diagnóstico y la mediana de duración del tratamiento con 5-ASA fue de 107 meses (rango intercuartílico: 22,5-187). La remisión endoscópica, definida por la ausencia de úlceras en la última colonoscopia completa, se observó en el 65% de los pacientes a los que se les realizó al menos una colonoscopia durante el seguimiento. El género masculino y las manifestaciones extraintestinales se asociaron con una menor probabilidad de lograr la remisión endoscópica. Nueve pacientes requirieron colectomía, pero en su mayoría poco después del diagnóstico de EC. Conclusiones: Los 5-ASA parecen ser beneficiosos a largo plazo en una quinta parte de los pacientes con EC cólica como única terapia de mantenimiento y deben considerarse en pacientes frágiles con EC con afectación exclusiva del colon.(AU)

Clinical Presentation, Management, and Evolution of Lymphomas in Patients with Inflammatory Bowel Disease: An ENEIDA Registry Study.

An increased risk of lymphoma has been described in patients with inflammatory bowel disease (IBD). The aims of our study were to determine the clinical presentation, the previous exposure to immunosuppressive and biologic therapies, and the evolution of lymphomas in patients with IBD. IBD patients with diagnosis of lymphoma from October 2006 to June 2021 were identified from the prospectively maintained ENEIDA registry of GETECCU. We identified 52 patients (2.4 cases of lymphoma/1000 patients with IBD; 95% CI 1.8-3.1). Thirty-five were men (67%), 52% had ulcerative colitis, 60% received thiopurines, and 38% an anti-TNF drug before lymphoma diagnosis. Age at lymphoma was lower in those patients treated with thiopurines (53 ± 17 years old) and anti-TNF drugs (47 ± 17) than in those patients not treated with these drugs (63 ± 12; p < 0.05). Five cases had relapse of lymphoma (1.7 cases/100 patient-years). Nine patients (17%) died after 19 months (IQR 0-48 months). Relapse and mortality were not related with the type of IBD or lymphoma, nor with thiopurines or biologic therapies. In conclusion, most IBD patients had been treated with thiopurines and/or anti-TNF agents before lymphoma diagnosis, and these patients were younger at diagnosis of lymphoma than those not treated with these drugs. Relapse and mortality of lymphoma were not related with these therapies.

Ustekinumab and vedolizumab for the prevention of postoperative recurrence of Crohn's disease: Results from the ENEIDA registry.

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.

Clinical and endoscopic outcomes of patients with colonic Crohn's disease treated with 5-aminosalicylates as monotherapy.

BACKGROUND: In spite of the lack of evidence regarding the clinical benefits of oral 5-aminosalicylic acid (5-ASA) compounds in Crohn's disease (CD), these drugs are frequently used in daily clinical practice, particularly for colonic CD. Our aim is to assess the use and clinical outcomes of 5-ASA of those patients with colonic CD treated with 5-ASA as monotherapy. METHODS: Patients diagnosed with isolated colonic CD and treated with 5-ASA but never exposed to immunosuppressants or biologicals were identified from the local databases of five referral centres. A retrospective review of clinical and endoscopic outcomes was performed. RESULTS: Out of 545 patients with isolated colonic CD, 106 (19%) were treated with oral 5-ASA in monotherapy as maintenance therapy. The median follow-up was 144 months (interquartile range [IQR], 48-234). Almost all of the patients (92%) presented an inflammatory pattern and 11% developed perianal disease. Half of the patients had already received 5-ASA at diagnosis, and the median duration of 5-ASA treatment was 107 months (IQR 22.5-187). Endoscopic remission, as defined by the absence of ulcers at the last complete colonoscopy, was observed in 65% of those patients undergoing at least one colonoscopy during follow-up. Male gender and extraintestinal manifestations were associated with a lower likelihood of achieving endoscopic remission. Nine patients required colectomy, but mostly soon after CD diagnosis. CONCLUSIONS: 5-ASA seems to be of benefit in the long-term in one fifth of patients with colonic CD as the only maintenance therapy and should be considered in fragile patients with Crohn's colitis.

Lessons learnt from the implementation of a colorectal cancer screening programme for lynch syndrome in a tertiary public hospital.

BACKGROUND: Lynch syndrome (LS) is the first cause of inherited colorectal cancer (CRC), being responsible for 2-4% of all diagnoses. Identification of affected individuals is important as they have an increased lifetime risk of multiple CRC and other neoplasms, however, LS is consistently underdiagnosed at the population level. We aimed to evaluate the yield of LS screening in CRC in a single-referral centre and to identify the barriers to its effective implementation. METHODS: LS screening programme included individuals with CRC < 70 years, multiple CRC, or endometrial cancer at any age. Mismatch repair (MMR) protein immunohistochemistry (IHC) analysis was performed in routine practice on the surgical specimen and, if MLH1 IHC was altered, MLH1 gene promoter methylation was analysed. Results were collected in the CRC multidisciplinary board database. LS suspected individuals (altered MMR IHC without MLH1 promoter methylation) were referred to the Cancer Genetic Counselling Unit (CGCU). If accepted, a genetic study was performed. Two checkpoints were included: review of the pathology data and verification of patient referral by a genetic counsellor. RESULTS: Between 2016 and 2019, 381 individuals were included. MMR IHC analysis was performed in 374/381 (98.2 %) CRC cases and MLH1 promoter methylation in 18/21 (85.7 %). Seventeen of the 20 LS suspected individuals were invited for referral at the CGCU. Two cases were not invited and the remaining patient died of cancer before completion of tumour screening. Fifteen individuals attended and a genetic analysis was performed in 15/20 (75 %) LS suspected individuals. Ten individuals were diagnosed with LS, in concordance with the IHC profile (2.7 % of the total cohort). This led to cascade testing in 58/75 (77.3 %) of the available adult relatives at risk, identifying 26 individuals with LS. CONCLUSIONS: Establishing a standardized institutional LS screening programme with checkpoints in the workflow is key to increasing the yield of LS identification.

The Genetic Diversity and Dysfunctionality of Catalase Associated with a Worse Outcome in Crohn's Disease.

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.

Performance of Screening Strategies for Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease: Results from the ENEIDA Registry of GETECCU.

(1) Aims: Patients receiving antitumor necrosis factor (anti-TNF) therapy are at risk of developing tuberculosis (TB), usually due to the reactivation of a latent TB infection (LTBI). LTBI screening and treatment decreases the risk of TB. This study evaluated the diagnostic performance of different LTBI screening strategies in patients with inflammatory bowel disease (IBD). (2) Methods: Patients in the Spanish ENEIDA registry with IBD screened for LTBI between January 2003 and January 2018 were included. The diagnostic yield of different strategies (dual screening with tuberculin skin test [TST] and interferon-×¥-release assay [IGRA], two-step TST, and early screening performed at least 12 months before starting biological treatment) was analyzed. (3) Results: Out of 7594 screened patients, 1445 (19%; 95% CI 18−20%) had LTBI. Immunomodulator (IMM) treatment at screening decreased the probability of detecting LTBI (20% vs. 17%, p = 0.001). Regarding screening strategies, LTBI was more frequently diagnosed by dual screening than by a single screening strategy (IGRA, OR 0.60; 95% CI 0.50−0.73, p < 0.001; TST, OR 0.76; 95% CI 0.66−0.88, p < 0.001). Two-step TST increased the diagnostic yield of a single TST by 24%. More cases of LTBI were diagnosed by early screening than by routine screening before starting anti-TNF agents (21% [95% CI 20−22%] vs. 14% [95% CI 13−16%], p < 0.001). The highest diagnostic performance for LTBI (29%) was obtained by combining early and TST/IGRA dual screening strategies in patients without IMM. (4): Conclusions: Both early screening and TST/IGRA dual screening strategies significantly increased diagnostic performance for LTBI in patients with IBD, with optimal performance achieved when they are used together in the absence of IMM.

Comparative efficacy and safety of infliximab and vedolizumab therapy in patients with inflammatory bowel disease: a systematic review and meta-analysis.

BACKGROUND AND AIMS: There are limited comparative data for infliximab and vedolizumab in inflammatory bowel disease patients. METHODS: We conducted a systematic review and meta-analysis to compare the efficacy and safety of infliximab and vedolizumab in adult patients with moderate-to-severe Crohn's disease or ulcerative colitis. RESULTS: We identified six eligible Crohn's disease and seven eligible ulcerative colitis trials that randomised over 1900 participants per disease cohort to infliximab or vedolizumab. In the Crohn's disease and ulcerative colitis cohorts, infliximab yielded better efficacy than vedolizumab for all analysed outcomes (CDAI-70, CDAI-100 responses, and clinical remission for Crohn's disease and clinical response and clinical remission for ulcerative colitis) during the induction phase, with non-overlapping 95% confidence intervals. In the maintenance phase, similar proportions of infliximab- or vedolizumab-treated patients achieved clinical response, clinical remission, or mucosal healing in both Crohn's disease and ulcerative colitis. For the safety outcomes, rates of adverse events, serious adverse events, and discontinuations due to adverse events were similar in infliximab- and vedolizumab-treated patients in both diseases. The infection rate was higher in infliximab for Crohn's disease and higher in vedolizumab when treating patients with ulcerative colitis. There was no difference between the treatments in the proportions of patients who reported serious infections in both indications. CONCLUSIONS: Indirect comparison of infliximab and vedolizumab trials in adult patients with moderate-to severe Crohn's disease or ulcerative colitis demonstrated that infliximab has better efficacy in the induction phase and comparable efficacy during the maintenance phase and overall safety profile compared to vedolizumab.

Recomendaciones para la selección del donante para la transferencia de microbiota fecal. Documento de posicionamiento avalado por la Societat Catalana de Digestologia, la Societat Catalana de Malalties Infeccioses i Microbiologia Clínica y el grupo GEMBIOTA de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica / Recommendations for stool donor selection for fecal microbiota transplant. Consensus document endorsed by the Catalan Society of Digestology, Catalan Society of Infectious diseases and Clinical microbiology and the GEMBIOTA group from Spanish Society of Infectious Diseases and Clinical Microbiology

La transferencia de microbiota fecal (TMF) es un tratamiento eficaz y seguro para tratar la infección recurrente por Clostridioides difficile. Es esencial extremar esfuerzos para que la TMF se realice con rigor y en base a los conocimientos científicos. La selección del donante de microbiota fecal es un punto clave del proceso para garantizar la seguridad del receptor. Es necesario disponer de protocolos de actuación que permitan a los clínicos actuar con las máximas garantías y minimizar los riesgos del procedimiento. Por este motivo, en Cataluña se ha constituido un grupo de trabajo multidisciplinario con el objetivo de establecer unas recomendaciones para la selección del donante de microbiota fecal.

Fecal microbiota transplantation (FMT) is an effective and safe treatment to treat recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and based on scientific knowledge. Selection of the fecal microbiota donor is a key point of the process to ensure recipient safety. It is necessary to have protocols of action that allow clinicians to act with the maximum guarantees and to minimize the risks of the procedure. For this reason, a multidisciplinary working group has been set up in Cataluña with the aim of establishing recommendations for the selection of the fecal microbiota donor.

Self-expandable metal stents versus endoscopic balloon dilation for the treatment of strictures in Crohn's disease (ProtDilat study): an open-label, multicentre, randomised trial.

BACKGROUND: Endoscopic balloon dilation (EBD) is the established endoscopic treatment for short strictures in Crohn's disease. Fully covered self-expandable metal stents (FCSEMS) have been used for endoscopic treatment of patients for whom EBD was unsuccessful. We aimed to determine the efficacy and safety of the two endoscopic treatments in patients with Crohn's disease with stenosis and compare the mean cost of both treatments. METHODS: This multicentre, open-label, randomised trial was done in 19 tertiary and secondary hospitals in Spain. Patients with Crohn's disease with obstructive symptoms and predominantly fibrotic strictures of less than 10 cm in length were eligible for inclusion. We excluded patients with stenosis treated with SEMS or EBD in the previous year and stenosis not accessible to a colonoscope. Patients were randomly assigned (1:1) to receive either EBD (EBD group) or FCSEMS (FCSEMS group) using a digital en-block randomisation system (block size of four). In the EBD group, dilation was done with a CRE Boston Scientific (Marlborough, MA, USA) pneumatic balloon with the diameter set at the discretion of the endoscopist; a maximum of two sessions of dilation were allowed with a minimum interval of 15-30 days between them. In the FCSEMS group, a 20 mm diameter Taewoong (Gimpo-si, South Korea) fully covered metal stent was placed; stent length was set at the discretion of the endoscopist. The primary outcome was to assess the efficacy of the endoscopic treatment, defined by the proportion of patients free of a new therapeutic intervention (EBD, FCSEMS, or surgery) due to symptomatic recurrence at 1 year of follow-up. Patients were analysed according to the intention-to-treat principle. Adverse events were recorded for all the patients; events were considered associated to be with the procedure when a causal association was possible, probable, or definite. This trial is registered with ClinicalTrials.gov, NCT02395354. FINDINGS: From Aug 28, 2013, to Oct 9, 2017, we assessed the eligibility of 99 patients, of whom 19 (19%) patients were excluded. Thus, 80 (81%) patients were randomly assigned to treatment: 39 (49%) patients to the FCSEMS group and 41 (51%) patients to the EBD group. 33 (80%) of 41 patients in the EBD group and 20 (51%) of 39 patients in the FCSEMS group were free of a new therapeutic intervention at 1 year (odds ratio [OR] 3·9 [95% CI 1·4-10·6]; p=0·0061). Two (3%) of 80 patients had severe adverse events (one [2%] patient in the EBD group and one [3%] patient in the FCSEMS group); both patients had perforations. INTERPRETATION: EBD is more effective than FCSEMS for Crohn's disease strictures, with a good safety profile for both treatments. FUNDING: Spanish National Institute of Health, Foundation of Spanish Society of Digestive Endoscopy, Catalan Society of Gastroenterology, and Taweoong.

EPAGE no es una estrategia eficaz para la gestión de colonoscopias durante la pandemia por COVID-19 / The EPAGE guidelines are not an effective strategy for managing colonoscopies during the COVID-19 pandemic

Introducción: La pandemia producida por el virus SARS-CoV-2 ha generado un grave impacto en el funcionamiento de las unidades de endoscopia digestiva. La Asociación Española de Gastroenterología y la Sociedad Española de Endoscopia Digestiva (AEG-SEED) han propuesto la utilización de la guía European Panel on the Appropriateness of Gastrointestinal Endoscopy II (EPAGE) para la gestión de las colonoscopias pospuestas.Objetivo: Evaluar la guía EPAGE como herramienta de gestión en comparación con el test de sangre oculta en heces inmunológico (TSOHi) y con una calculadora de riesgo (CR), que incluye la edad, el sexo y el TSOHi, para la detección de cáncer colorrectal (CCR) y lesión significativa colónica (LSC).Métodos: Estudio unicéntrico prospectivo. Se incluyeron 743 pacientes derivados para una colonoscopia diagnóstica. Se clasificó cada solicitud según EPAGE en apropiada, indeterminada e inapropiada. Se les entregó un TSOHi y se calculó el valor de la CR.ResultadosEl TSOHi (p<0,001), pero no EPAGE (p = 0,742), fue una variable independiente de riesgo de CCR. El área bajo la curva receiver operating characteristic (ROC) de EPAGE, TSOHi y CR fue: 0,61(IC 95% 0,49 a 0,75), 0,95 (0,93 a 0,97) y 0,90 (0,87 a 0,93) para CCR; y 0,55 (0,49 a 0,61), 0,75 (0,69 a 0,813) y 0,78 (0,73 a 0,83) para LSC, respectivamente. El número necesario de colonoscopias para detectar un CCR y una LSC fue de 38 y siete para EPAGE, de siete y dos para TSOHi, y de 19 y cuatro para CR ≥ cinco puntos, respectivamente.Conclusión: La EPAGE, a diferencia del TSOHi, no es adecuada para seleccionar a los pacientes candidatos a colonoscopia diagnóstica para la detección de CCR. El TSOHi, en combinación con la edad y el sexo, es la estrategia correcta para gestionar la demanda de endoscopia en un escenario de acceso restrictivo.

Introduction: The pandemic caused by the SARS-CoV-2 virus has had a serious impact on the functioning of gastrointestinal endoscopy Units. The Asociación Española de Gastroenterología (AEG) and the Sociedad Española de Endoscopia Digestiva (SEED) have proposed the EPAGE guidelines for managing postponed colonoscopies.ObjectiveTo evaluate the EPAGE guidelines as a management tool compared to the immunologic faecal occult blood test (iFOBT) and compared to risk score (RS) that combines age, sex and the iFOBT for the detection of colorectal cancer (CRC) and significant bowel disease (SBD).Methods: A prospective, single-centre study enrolling 743 symptomatic patients referred for a diagnostic colonoscopy. Each order was classified according to the EPAGE guidelines as appropriate, indeterminate or inappropriate. Patients underwent an iFOBT and had their RS calculated.Results: The iFOBT (p<0.001), but not the EPAGE guidelines (p = 0.742), was an independent predictive factor of risk of CRC. The ROC AUCs for the EPAGE guidelines, the iFOBT and the RS were 0.61 (95% CI 0.49-0.75), 0.95 (0.93-0.97) and 0.90 (0.87-0.93) for CRC, and 0.55 (0.49-0.61), 0.75 (0.69-0.813) and 0.78 (0.73-0.83) for SBD, respectively. The numbers of colonoscopies needed to detect a case of CRC and a case of SBD were 38 and seven for the EPAGE guidelines, seven and two for the iFOBT, and 19 and four for a RS ≥5 points, respectively.Conclusion: The EPAGE guidelines, unlike the iFOBT, is not suitable for screening candidate patients for a diagnostic colonoscopy to detect CRC. The iFOBT, in combination with age and sex, is the most suitable strategy for managing demand for endoscopy in a restricted-access situation

Recommendations for stool donor selection for fecal microbiota transplant. Consensus document endorsed by the Catalan Society of Digestology, Catalan Society of Infectious diseases and Clinical Microbiology and the GEMBIOTA group from Spanish Society of Infectious Diseases and Clinical Microbiology.

Fecal microbiota transplantation (FMT) is an effective and safe treatment to treat recurrent Clostridioides difficile infection. It is essential to make every effort to perform FMT rigorously and based on scientific knowledge. Selection of the fecal microbiota donor is a key point of the process to ensure recipient safety. It is necessary to have protocols of action that allow clinicians to act with the maximum guarantees and to minimise the risks of the procedure. For this reason, a multidisciplinary working group has been set up in Cataluña with the aim of establishing recommendations for the selection of the fecal microbiota donor.