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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.

Stricture formation is a common complication of Crohn's disease, resulting from the disease process, surgery, or drugs. Endoscopic balloon dilation has an important role in the management of strictures, with emerging techniques, such as endoscopic electroincision and stenting, showing promising results. The underlying disease process, altered bowel anatomy from disease or surgery, and concurrent use of immunosuppressive drugs can make endoscopic procedures more challenging. There is an urgent need for the standardisation of endoscopic procedures and peri-procedural management strategies. On the basis of an extensive literature review and the clinical experience of the consensus group, which consisted of representatives from the Interventional Inflammatory Bowel Disease Group, we propose detailed guidance on all aspects of the principles and techniques for endoscopic procedures in the treatment of inflammatory bowel disease-associated strictures.

OBJECTIVES 1)To analyze evidence about poor adherence / non-adherence including their prevalences, associated factors, and interventions in ulcerative colitis (UC) patients; 2)To provide a framework to improve poor adherence / non-adherence. METHODS A qualitative approach was applied. A literature review was performed using Medline. Primary searches were performed with Mesh and free texts to identify articles that analyzed prevalence, causes, associated factors, and interventions designed to improve poor adherence/ non-adherence in UC patients. The studies' quality was evaluated using the Oxford scale. The results were presented and discussed in a nominal group meeting, comprising a multidisciplinary committee of six gastroenterologists, one psychologist, one nurse, and one patient. Several overarching principles and recommendations were generated. A consensus procedure was implemented via a Delphi process during which each committee member produced a score ranging from 0 = totally disagree to 10 = totally agree. Agreement was considered if at least 70% of the participants voted ≥7. RESULTS The literature review included 75 articles. Non-adherence rates ranged from 7%-72%. We found a great variability in the methods employed to assess adherence, associated factors, and interventions designed to improve adherence. Overall, eight overarching principles and six recommendations were generated, all of them achieving the pre-established agreement level, including, among others, the identification, classification, and management of non-adherence. CONCLUSIONS Poor adherence / non-adherence are common in UC patients, being a relevant clinical concern. Health professionals should address this issue and actively involve the patients in implementing effective and individualized interventions to improve adherence.

BACKGROUND AIMS Current therapeutic goals in ulcerative colitis (UC) include clinical and endoscopic remission, named mucosal healing (MH). Despite MH, a proportion of patients suffer a clinical relapse, which has been related to histological inflammation. We aimed to identify which histopathological features or histopathological index cut-off was associated with endoscopic relapse (ER) in UC patients with MH. METHODS Retrospective analysis of UC patients who underwent surveillance colonoscopy showing complete MH (endoscopic Mayo subscore=0) with random biopsies, and at least one more endoscopy along the follow-up. After a consensus meeting, expert pathologist performed histological assessment according to Simplified Geboes Score (SGS), Nancy Index (NI) and Robarts Histopathological Index (RHI). Other histopathological features were also evaluated. Patients were followed until ER or last endoscopy performed showing persistence of MH. RESULTS A total of 95 patients (150 colonoscopies) were included. After mean follow-up of 31.2 months (SD 21.7), 33 patients (34.7%) suffered ER. Neutrophils in lamina propria (OR 2.6; P = 0.037), within the epithelium (OR 2.6; P = 0.03), SGS ≥3.1 (OR 2.6; P = 0.037), NI ≥2 (OR 2.6; P = 0.03) and RHI ≥5 (OR 2.6; P = 0.037) were associated with ER in univariate analysis. In multivariate analysis, eosinophils in the lamina propria (HR 2.5; P = 0.01) and clinical remission

Background Post-marketing data are required to confirm the durability and the long-term benefit and safety of UST in CD in clinical practice. Our aims were: (1) to evaluate the retention rate of UST in CD patients and to identify predictive factors of UST discontinuation; (2) to assess UST short-term effectiveness; (3) to analyse the durability of the response to UST in the long-term; and (4) to evaluate the safety of UST in clinical practice. Methods Retrospective, multicentre study (>60 centres). Patients with active CD [(Harvey–Bradshaw (HBI) >4)] that received at least one dose of UST intravenously before July 2018 were included. Clinical activity plus biochemical parameters were assessed at every UST administration. Clinical remission was defined as HBI score ≤4, and clinical response as a decrease in HBI ≥3 points. Loss of efficacy was defined as reappearance of symptoms that led to intensify the treatment dose, add another medication to control CD, switching or surgery in patients with short-term remission. The retention rate of UST treatment and the cumulative incidence of loss of efficacy were evaluated by survival curves, and predictive factors were assessed by Cox-regression. The short-term response was evaluated at week 8 and after the induction (week 16). Factors associated with short-term remission were assessed by multivariate analysis. Adverse events were recorded. Data quality was assured by remote monitoring. Results 331 CD patients have been included up to date (Table 1). The incidence rate of UST discontinuation was 15% per patient-year of follow-up: 8%, 13% and 20% at 6, 12 and 18 months (Figure 1). Previous surgery was the only factor associated with a higher risk of UST discontinuation [Hazard ratio (HR) = 2.03, 95% confidence interval (CI) = 1.1–3.6]. Short-term efficacy is shown in Figure 2. Previous surgery (OR = 0.3, 95% CI = 0.2–0.6) and higher HBI score at baseline (OR = 0.8, 95% CI=0.8–0.9) were associated with an impaired response to UST at week 16. The cumulative incidence of loss of response was 32% per-patient-year of follow-up (Figure 3); A higher HBI score at baseline was associated with a higher risk of losing response (HR = 1.2, 95% CI = 1.1–1.3). Neither the concomitant treatment with immunosuppressants nor the number of previous biologics were associated with UST short- and long-term benefit. Thirty adverse events were reported in 25 (7%) patients (Table 2). Conclusion Sustain is the largest real clinical practice study of UST to treat CD patients with the longest follow-up reported to date. UST was demonstrated to be effective in real-world use in the short and long run. Safety was consistent with the known profile of UST.

Background and aims Diagnosis and monitoring of ulcerative colitis (UC) includes conventional colonoscopy. This procedure is invasive and does not exclude small-bowel Crohn’s disease (CD). Current therapeutic goals include mucosal healing which may lead to an increased number of endoscopic procedures in many patients. The small-bowel colon capsule endoscopy (SBC-CE) system visualizes the small bowel and colon. The aim of this study was to evaluate the performance and adverse events of SBC-CE in patients with UC. Methods This was a prospective, feasibility study involving two study sites. Patients with active UC underwent SBC-CE and colonoscopy. Kappa statistics were performed to assess the agreement between SBC-CE and colonoscopy. Adverse events (AEs) data were collected throughout and following the procedure. Results In total, 30 consecutive patients were recruited, and 23 of those were included in the final analysis. For the primary end point, evaluation of the extent of UC disease in the colon, the percent agreement between SBC-CE and colonoscopy was moderate (56.5 %); kappa coefficient 0.42. The percent agreement between SBC-CE and colonoscopy for UC disease activity, based on Mayo endoscopic sub-score, was 95.7 %; kappa coefficient 0.86. Disease activity in the more proximal small bowel was detected in two patients with SBC-CE. No SBC-CE device-related AEs were reported. Conclusions When comparing SBC-CE to conventional colonoscopy, there was a moderate agreement for the extent of UC disease and a very good overall agreement between the two modalities for UC disease activity.

Background and study aims Chromoendoscopy with targeted biopsy is the technique of choice for colorectal cancer screening in longstanding inflammatory bowel disease. We aimed to analyze results of a chromoendoscopy screening program and to assess the possibility of identifying low-risk dysplastic lesions by their endoscopic appearance in order to avoid histological analysis. Materials and methods We retrospectively reviewed chromoendoscopies performed between February 2011 and June 2017 in seven Spanish hospitals in a standardized fashion. We analyzed the findings and the diagnostic yield of the Kudo pit pattern for predicting dysplasia. Results A total of 709 chromoendoscopies (569 patients) were reviewed. Median duration of disease was 16.7 years (SD 8.1); 80.4 % had ulcerative colitis. A total of 2025 lesions (3.56 lesions per patient) were found; two hundred and thirty-two lesions were neoplastic (11.5 %) (223 were LGD (96.1 %), eight were HGD (3.4 %), and one was colorectal cancer (0.5 %). The correlation between dysplasia and Kudo pit patterns predictors of dysplasia (≥ III) was low, with an area under the curve of 0.649. Kudo I and II lesions were correctly identified with a high negative predictive value (92 %), even by non-experts. Endoscopic activity, Paris 0-Is classification, and right colon localization were risk factors for dysplasia detection, while rectum or sigmoid localization were protective against dysplasia. Conclusions Chromoendoscopy in the real-life setting detected 11 % of dysplastic lesions with a low correlation with Kudo pit pattern. A high negative predictive value would prevent Kudo I and, probably, Kudo II biopsies in the left colon, reducing procedure time and avoiding complications.

Thiopurines are classically used in Crohn’s disease (CD). Treatment fails in a proportion of patients either due to adverse events (AE) or lack of efficacy. Increasing use of anti-TNFα biologic drugs may have had impact on thiopurines usage. To evaluate the evolving use of azathioprine (AZA) monotherapy in the era of biologics. The study retrospectively analyzed clinical records of all CD patients who started treatment with AZA monotherapy at our center since 1990. Dates of starting AZA and treatment failure (TF) were collected. We defined AZA TF if it was withdrawn due to lack of efficacy or AE, or biologics were added. A total of 383 patients were included: 46.5% were males and mean age was 31 (range 17–84) years. Median follow-up was 43 (range 0.2–289) months. Overall, 147 patients (38%) experienced TF. Median cumulative survival time of AZA was 126 (95% CI 105–147) months. Proportion of patients with AZA TF increased along time: 7 patients in 1990–1995 (4.7% of all TF); 8 in 1996–2000 (5.4%); 22 in 2001–2005(15%); 41 in 2006–2010 (28%); 69 in 2011–2014 (47%) (p = 0.04). 7%, 21%, 4%, 45%, and 33.3% of patients moved to biologics in each period, respectively (χ2 = 13.07; p

INTRODUCTION: COVID-19 has altered the usual practice of medicine and the state of emergency declared in Spain on March 14th has considerably changed the activity of inflammatory bowel disease (IBD) units. The aim of this study was to evaluate the consequences of COVID-19 on the IBD Unit's activity and provide information on restructuring with available resources. METHODS: an observational study was performed in a referral hospital in Madrid (Spain). Type of appointment, loss of follow-up, hospital admission, treatment changes, endoscopic activity, surgeries and blood tests were evaluated between March 15th and May 15th, 2020. This data was compared with the usual activity a year before. RESULTS: among the 510 patients included, 476 (93.33 %) received had a remote consultation, representing an increase of 92.38 % compared with the previous year (0.95 %). There was a loss of follow-up in 26 patients (5.1 %) vs 15 (3.58 %) the previous year. A total of 60 (35.09 %) blood tests, 64 (76.19 %) endoscopies and all scheduled surgeries were suspended. Besides, 484 (94.9 %) patients remained adherent vs 417/419 (99.5 %) in the pre-pandemic period and 48 (9.41 %) reported symptoms of an IBD flare. Thirty-nine (7.6 %) patients developed symptoms suggestive of COVID-19. CONCLUSION: a large number of tests and on-site outpatient visit consultations were suspended. However, a rapid adaptation to telemedicine allowed these patients to be closely followed up. Although it was possible to maintain therapeutic compliance, with a loss to follow-up slightly higher than the previous year, suspensions and delays of tests could have significant negative consequences in the long term.

Purpose: biosimilar infliximab (CTP-13) has been recently approved for the treatment of several immune-mediated inflammatory disorders, including inflammatory bowel disease (IBD). Comparative studies between this biosimilar and original infliximab in the real clinical practice are scarce. The objective of this study was to compare short and long-term safety and efficacy of original (O) and biosimilar infliximab (B-IFX) in biologic-naive, IBD patients in the real life clinical practice. Methods: a retrospective, multicentric study was performed in five Spanish hospitals. Consecutive IBD, biologic-naive patients from an historic cohort who initiated O-IFX from January 2013 were compared with biologic-naive patients, who started treatment with B-IFX since its approval in January 2015. The evaluation of efficacy was assessed after the induction phase, at week 14 and week 54 of treatment. Time to dose escalation or treatment persistence of both O-IFX and B-IFX was also considered. The appearance of serious adverse events was recorded. Results: two hundred and thirty-nine IBD biologic-naive patients who started with O-IFX or B-IFX were included: 153 patients were diagnosed with Crohn’s disease (95 treated with O- and 58 treated with B-IFX) and 86 with ulcerative colitis (40 received O- and 46 received B-IFX). At weeks 14 and 54, both O-IFX and B-IFX groups reached a similar clinical response and remission rates. Time to dose escalation, treatment persistence and safety profile were comparable between both groups. Conclusions: this long-term real-life experience provides additional evidence of the similarity of O- and B-IFX CTP-13 in terms of efficacy and safety in IBD patients.

Ustekinumab is effective in Crohn's disease. However, a substantial proportion of patients will not respond or lose response to ustekinumab. The current evidence to support the effectiveness of dose-optimisation for ustekinumab nonresponse is limited., info:eu-repo/semantics/published

Background and Aims An expanding number of monogenic defects have been identified as causative of severe forms of very early-onset inflammatory bowel diseases [VEO-IBD]. The present study aimed at defining how next-generation sequencing [NGS] methods can be used to improve identification of known molecular diagnosis and to adapt treatment. Methods A total of 207 children were recruited in 45 paediatric centres through an international collaborative network [ESPGHAN GENIUS working group] with a clinical presentation of severe VEO-IBD [n = 185] or an anamnesis suggestive of a monogenic disorder [n = 22]. Patients were divided at inclusion into three phenotypic subsets: predominantly small bowel inflammation, colitis with perianal lesions, and colitis only. Methods to obtain molecular diagnosis included functional tests followed by specific Sanger sequencing, custom-made targeted NGS, and in selected cases whole exome sequencing [WES] of parents-child trios. Genetic findings were validated clinically and/or functionally. Results Molecular diagnosis was achieved in 66/207 children [32%]: 61% with small bowel inflammation, 39% with colitis and perianal lesions, and 18% with colitis only. Targeted NGS pinpointed gene mutations causative of atypical presentations, and identified large exonic copy number variations previously missed by WES. Conclusions Our results lead us to propose an optimised diagnostic strategy to identify known monogenic causes of severe IBD.

Background and aims Our objective was to define, describe and organize (on the basis of consensus) the patient's preferences in the management of ulcerative colitis (UC), in order to further incorporate them in daily practice and improve patients satisfaction, adherence to the treatment and quality of care. Methods Qualitative study. A narrative literature review in Medline using Mesh and free-text terms was conducted to identify articles on UC patient preferences as well as clinical scenarios that may influence the preferences. The results were presented and discussed in a multidisciplinary nominal group meeting composed of six gastroenterologists, one primary care physician, one nurse practitioner and one expert patient. Key clinical scenarios and patient preferences were then defined, generating a series of points to consider and recommendations. The level of agreement with the final selection of preferences was established following a Delphi process. Results The narrative review retrieved 69 articles of qualitative design and moderate quality. The following key clinical scenarios were identified: diagnosis, follow-up, surgery, and special situations/patients profiles such as adolescents or women. Patient preferences were classified into information, treatment (pharmacological and non-pharmacological), follow-up, relations with health professionals, relations with the health system and administration. Finally, 11 recommendations on patient preferences for UC in relation to its management reached the level of agreement established. Conclusion The consensual description of patient's preferences contribute to identify different areas for improvement in healthcare practice.

Extraintestinal manifestations, in general, and in particular arthropathies, are a common problem in patients with inflammatory bowel disease. In fact, the relationship between those 2 entities is close and there are increasingly more data which suggest that the bowel plays a significant role in the aetiopathogenesis of spondyloarthritis. The association of inflammatory bowel disease with any kind of spondyloarthritis represents a challenging clinical scenario. It is therefore necessary that both gastroenterologists and rheumatologists work together and establish a fluent communication that enables the patient to receive the most appropriate treatment for each specific situation. The aim of this review is to make some recommendations about the treatment of patients with inflammatory bowel disease and associated spondyloarthritis, in each different clinical scenario., Las manifestaciones extraintestinales en general, y entre ellas las articulares en particular, suponen un problema frecuente en los pacientes con enfermedad inflamatoria intestinal. De hecho, la relación entre ambas entidades parece estrecha y cada vez hay más datos que sugieren que el intestino desempeña un importante papel en la patogenia de las espondiloartritis. La asociación de la enfermedad inflamatoria intestinal con algún tipo de espondiloartritis supone un escenario clínico complejo. Es necesario, por tanto, que gastroenterólogos y reumatólogos puedan trabajar juntos y establecer una comunicación fluida que permita a cada paciente recibir el tratamiento más adecuado para cada situación concreta. El objetivo de esta revisión es el de establecer unas recomendaciones sobre el tratamiento de los pacientes con enfermedad inflamatoria intestinal y espondiloartritis asociada, en cada uno de los distintos escenarios clínicos

Background The exhaustive registry of COVID-19 cases in patients with IBD is a unique opportunity to learn how to deal with this infection, especially in reference to the management of immunosuppressive treatment, isolation measures or if the disease is more severe in IBD patients due to immunosuppression. With these premises, the aims of this study were to know the incidence and characteristics of COVID-19 in the ENEIDA cohort during the first wave of the pandemic; the outcomes among those under immunosuppressants/biologics for IBD; the risk factors for contracting the infection and poor outcomes; and the impact of the infection after three-month follow-up. Methods Prospective observational cohort study of all IBD patients with COVID-19 included in the ENEIDA registry (with 60.512 patients in that period) between March and July 2020, with at least 3 months of follow-up. Any patient with a confirmed (by PCR or SARS-CoV-2 serology) or probable (suggestive clinical picture) infection was considered as a case. Results A total of 484 patients with COVID-19 from 63 centres were included: 247 Crohn’s disease, 223 ulcerative colitis and 14 unclassified colitis; median age 52 years (IQR: 42–61), 48% women and 44% ≥1 comorbidity. Diagnosis was made by PCR: 63% and serology: 35%. The most frequent symptoms: fever (69%), followed by cough (63%) and asthenia (38%). During lockdown 78% followed strict isolation. 35% required hospital admission (ICU: 2.7%) and 12% fulfilled criteria for SIRS upon admission. 16 patients died from COVID-19 (mortality:3.3%). 12% stop IBD medication during COVID-19. At 3 months, taken into account all included cases, 76% were in remission of IBD. Male gender (OR 1.56; 95%CI:1–2.4, p=0.05), ≥40 years of age (OR 2.55; 95% CI:1.4–4.8; p=0.004), Charlson score ≥1 (OR 2.1; 95% CI:1.3–3.5; p=0.004), and systemic steroids Conclusion IBD does not seem to worsen the prognosis of COVID-19, even when immunosuppressants and biological drugs are used. Age and comorbidity are the most important prognostic factors for more severe COVID-19 in IBD patients. The use of aminosalicylates and the risk of a worse outcome deserves a deeper analysis. Funded by the Carlos III Health Institute (COV20 / 00227).

To evaluate numerous publications that question the bone and extraosseous benefits of vitamin D diet supplementation based on results, which often transcend to public opinion, but are not well interpreted. This may have negative consequences on compliance of patients under vitamin D supplementation. Critical appraisal of several articles on vitamin D supplementation and its relationship with fractures, falls, cardiovascular diseases, and cancer incidence. Such publications have certain limitations (i.e. patients excluded because of a diagnosis of osteoporosis, or at a higher risk for fractures and falls, or because they have a vitamin D deficiency, etc.), and conclusions and/or subsequent recommendations should be approached with caution. Our research shows that patients with osteoporosis, vitamin D deficiency, and at high risk of fractures and falls should not discontinue vitamin D supplementation (often associated with calcium). It is becoming increasingly evident that patients with hypovitaminosis D are those that gain a maximal benefit from vitamin D supplementation.

Resumen Introduccion La complejidad y el volumen crecientes de los pacientes con enfermedad inflamatoria intestinal (EII) obligan a desarrollar equipos multidisciplinares. La enfermeria especializada deberia ser parte de estas unidades tal y como se recoge en diferentes documentos de consenso. Objetivos Evaluar el impacto que la incorporacion de la enfermeria a la Unidad de EII del Hospital Universitario Puerta de Hierro Majadahonda (HUPHM) ha tenido desde el punto de vista asistencial, economico e investigador. Metodos Recogida prospectiva de la actividad desempenada por la enfermera de la Unidad de EII del HUPHM desde marzo del 2010 hasta diciembre del 2014. Resultados En este periodo se ha producido un aumento progresivo de la demanda asistencial, que ha alcanzado los 1.558 pacientes atendidos por nuestra Unidad. La asistencia proporcionada por la enfermera alcanzo un total de 5.293 correos electronicos y de 678 llamadas telefonicas. Con ello, se estima que esta actividad ha supuesto un ahorro de 3.504 consultas medicas presenciales asi como de 852 visitas al Servicio de Urgencias. Otras actividades realizadas han sido la monitorizacion de tratamientos con medicamentos biologicos y no biologicos (8.371 controles analiticos), la extraccion de 342 analiticas, el seguimiento de 1.047 pruebas diagnosticas e interconsultas a otras especialidades medicas, la educacion sanitaria en la autoadministracion de medicamentos a 114 pacientes, la realizacion de 158 granulocitoaferesis y la participacion en 25 proyectos de investigacion. Conclusiones La incorporacion de la enfermera especializada a la Unidad de EII tiene un gran impacto beneficioso tanto desde el punto de vista asistencial y economico como investigador.

Introduction Multidisciplinary units are needed because of the growing complexity and volume of patients with inflammatory bowel disease (IBD). Objectives To evaluate the healthcare, economic and research impact of incorporating a nurse into the IBD unit of the Puerta de Hierro Majadahonda University Hospital. Methods We prospectively recorded the activity carried out by the nurse of the IBD unit from March 2010 to December 2014. Results During this period, healthcare demand progressively increased, with 1558 patients being attended by our unit. The healthcare provided by the nurse included 5293 electronic mails and 678 telephone calls. We estimated that this activity represented a saving of 3504 in-person medical consultations and 852 accident and emergency department visits. Other activities consisted of monitoring treatments with biological and non-biological agents (8371 laboratory tests), extraction of 342 blood samples, follow-up of 1047 diagnostic tests and consultations with other medical specialties, health education in self-administration of drugs in 114 patients, the performance of 158 granulocyte apheresis procedures, and participation in 25 research projects. Conclusion The incorporation of a specialised nurse in an IBD unit had major economic, healthcare and research benefits.

Copyright © 2018 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved, Clinical indexes are useful for standardising disease activity. However, despite widespread use, no score has been validated in clinical practice.

Resumen Introduccion Nuestro objetivo fue evaluar el impacto clinico y la seguridad, asi como estimar el gasto de la capsula endoscopica (CE) en nuestro centro. Resultados Se analizaron retrospectivamente los estudios realizados en nuestro centro desde el ano 2009 hasta 2012. Las indicaciones mas frecuentes fueron el estudio de anemia (39%),el estudio de la hemorragia digestiva de origen incierto (HDOO) (19%) y de la enfermedad inflamatoria intestinal (EII) (18%). Se encontraron hallazgos positivos en un 51% de los casos, lo que tuvo impacto clinico en el 36,5%. La EII fue la indicacion en la que la CE tuvo mayor impacto clinico (74,5%, p Una aproximacion al gasto de las exploraciones recogidas supone una inversion de al menos 132.600 €; dado que el 63,5% de las exploraciones no tuvo impacto clinico quiere decir que la inversion de hasta 84.200 € no tuvo repercusion en el manejo de los pacientes. En aquellos pacientes que recibieron CE por un cuadro de HDOO se relaciono la realizacion precoz de la prueba ( Conclusiones En nuestra experiencia, la realizacion de la CE tuvo mayor impacto clinico en el estudio de la EII, y de la HDOO si se realiza de forma precoz; por el contrario, seria necesario un esfuerzo en mejorar las indicaciones de CE en el estudio de anemia para conseguir un mayor impacto clinico en este contexto.

Objective: to describe the experience at two tertiary centres during the first year of use of magnetic resonance enterography (MRE) for the management of Crohn's disease (CD): indications and influence of the technique in clinical decision making. Material and method: retrospective descriptive study in which patients who underwent MRE were included consecutively. Epidemiological and clinical data were collected from the patients, as well as the indication for the study and how it influenced clinical decision making in the 10 days following the radiological study. Results: 24 MREs were performed in suspected CD and 126 known CD; partial bowel obstruction in 53 patients (42%), monitoring of medical treatment in 34 (27%), due to incomplete ileocolonoscopy in 16 (13%), extension study of the small intestine in 15 (12%) and suspected complicated CD in 8 patients (6%). The MRE influenced in a change in treatment in 83 (55.3%) patients: 16 (10.7%) started with immunosuppressants, 41 (27.3%) with anti-TNFα were started on or switched, 15 (10%) were ordered surgery and in 3 (2%) changed from combined therapy to monotherapy. The MRE had less influence on clinical decision making in the group in which the indication was suspected CD (p < 0.05). Conclusions: the use of MRE helped on decision making in more than half of patients, especially with regards to decisions related to the use of biological therapies and the indication for surgery. MRE was less useful in suspected CD patients.

Thiopurines (azathioprine and mercaptopurine) are one of the immunosuppressive mainstays for the treatment of inflammatory bowel disease. In spite of its widespread use, thiopurine metabolism is still not fully understood, and a significant proportion of patients suffer toxicity or lack of efficacy. Different enzymatic pathways with individual variations constitute a pharmacogenetic model that seems to be suitable for monitoring and therapeutic intervention. This review is focused on current concepts and recent research that may help clinicians to rationally optimise thiopurine treatment in patients with inflammatory bowel disease.

Resumen Introduccion La enfermedad inflamatoria intestinal (EII) es un factor de riesgo independiente para presentar fenomenos tromboembolicos (FTE). Evaluamos la prevalencia y los posibles factores de riesgo asociados a presentar FTE en pacientes con EII en nuestro centro. Material y metodos Se recogieron los datos de forma retrospectiva desde enero de 1995 hasta diciembre de 2011, obteniendo un total de 23 pacientes. Un 61% habia sido diagnosticado de enfermedad de Crohn (EC) y un 39% de colitis ulcerosa (CU) segun los criterios habituales. Resultados Utilizando la clasificacion de Montreal, el 58% de los pacientes con EC tenia un patron inflamatorio (B1), el 25% un patron estenosante (B2) y el 17% un patron fistulizante (B3). Respecto a la localizacion, la mitad de los pacientes tenian afectacion ileocolica (L3), un tercio afectacion colica (L2) y el resto afectacion ileal (L1). Entre los pacientes con CU segun la clasificacion de Montreal, el 78% sufria una colitis extensa (E3), el 11% tenia afectacion de colon izquierdo (E2) y el 11% proctocolitis (E1). Durante el episodio, casi la mitad de los pacientes con CU tenian actividad inflamatoria severa (S3: 44%), un 33% actividad leve-moderada (S1: 22%; S2: 11%) y solo el 22% se encontraba en periodo quiescente (S0). De forma global, en el momento del FTE, el 48% de los pacientes tenia actividad leve-moderada y el 22% actividad severa. Asimismo, un 44% se encontraban hospitalizados en el momento de sufrir el episodio. En la CU se encontro un aumento de la prevalencia entre aquellos que se encontraban ingresados (66%). Ningun paciente tenia antecedentes familiares, 2 de ellos (9%) presentaban trombofilia asociada y un 26% eran fumadores activos. No hubo ningun fenomeno durante la gestacion. Solo una paciente tomaba anticonceptivos en el momento de sufrir el episodio. El FTE que se produjo con mayor frecuencia fueron las trombosis venosas profundas (TVP) de miembros inferiores (55%) seguidas de la tromboembolia pulmonar (TEP) (25%). Conclusiones Los FTE en la EII son relativamente frecuentes, con un importante impacto en la morbimortalidad de estos pacientes. En nuestra serie supusieron factores de riesgo para presentarlos la afectacion intestinal mas extensa (en cualquiera de los grupos) y la actividad inflamatoria severa. No se encontro una asociacion significativa entre los factores de riesgo clasicos como el uso de anticonceptivos, el embarazo, las enfermedades de la coagulacion o el habito tabaquico y el riesgo de presentar fenomenos tromboembolicos.

To evaluate effectiveness and safety of adalimumab in CD patients of the Madrid area and identify predictors of response.Multicenter retrospective survey of all CD patients treated with adalimumab in 9 hospitals of the Madrid area (Spain). Univariate and multivariate analysis of predictors of response was performed.174 patients included (50% males) with a median follow-up of 40 weeks. 30% had active perianal fistulizing disease at the beginning of the therapy with adalimumab. 59% had been previously treated with infliximab, being the lost of response (42.2%) the most frequent cause of withdrawal of the drug. 33% of patients needed dose escalation from every-other week to every week. The median time for this dose escalation was 33 weeks (range 2-120). The percentages of complete response at 4 weeks, 6 months and end of follow-up were 63, 70 and 63% in luminal disease and 49, 50 and 41% in perianal disease respectively. The prevalence of adverse events was 18% (most frequent was: 5 abscesses) causing the withdrawal of the drug in 21% of them.Adalimumab is effective and safe for the management of CD, even in refractory cases to infliximab.

Aliment Pharmacol Ther 2011; 34: 544–554 Summary Background Low thiopurine-methyl-transferase (TPMT) activity and high 6-thioguanine-nucleotide (6TGN) concentrations have been linked to therapeutic success in inflammatory bowel disease patients treated with thiopurines; however, this has not been implemented in clinical practice. Aim To identify a therapeutic threshold value for TPMT or 6TGN concentrations, and their capability to predict treatment safety and efficacy. Methods Prospective multicentre study including steroid-resistant/dependent patients starting thiopurines. The TPMT activity was determined at inclusion (>5 U/mL required). Azathioprine metabolites [6TGN, 6-methyl-mercaptopurine ribonucleotides (6MMP), and 6TGN/6MMP and 6TGN/TPMT ratios] were periodically monitored during steroid tapering and after withdrawal for 6 months or until a new flare occurred. Results A total of 113 patients were analysed (62% clinical response). Areas under the receiver operating characteristic (ROC) curve (AUC) relating clinical response and metabolite levels at 2, 4 and 6 months after steroid withdrawal were less than 0.7. The AUCs relating final response and initial TPMT activity or metabolite concentrations at 2, 4, 8 and 16 weeks after starting thiopurines were less than 0.7. No cut-off point with worthwhile sensitivity/specificity was found. Eight (7%) patients developed thiopurine-related toxicity that could not be linked to TPMT activity or 6TGN levels. Conclusions Our results do not support determination of TPMT activity or 6TGN concentrations to predict treatment outcome, and no useful serum metabolites threshold value to adjust the drug’s dose was identified.

Immunosuppressive or biological treatment in patients with inflammatory bowel disease can modify the natural history of their disease, although these treatments are not universally effective and can have severe adverse effects. Attempts have been made to identify predictive factors of response to the various therapeutic options in order to aid the choice of the most appropriate therapeutic alternative in each patient. The possibility of modifying any one of these predictive factors would be of great interest since it would provide the opportunity to alter the course of the disease. Epidemiological, biological, clinical, endoscopic, radiological, genetic and even proteomic markers have been studied, in addition to others related to the disease itself or to specific treatments. The present article briefly discusses the real use of each of these markers and the evidence supporting their utility.

Background: The aim was to evaluate the efficacy and tolerance of oral and intravenous iron treatment in anemic inflammatory bowel disease (IBD) patients, considering both hematological and quality-of-life outcomes. Methods: We performed a prospective multicenter study in IBD patients with iron deficiency anemia. Patients having hemoglobin >10 g/dL were prescribed oral ferrous sulfate. If hemoglobin

Efficacy of infliximab in Crohn's disease (CD) showed by randomized controlled trials must be confirmed in clinical practice. We aimed to evaluate efficacy and safety of infliximab in CD patients of the Madrid area, looking for clinical predictors of response.Multicenter retrospective survey of all CD patients treated with infliximab in 8 University hospitals of the Madrid area (Spain) with a minimum follow up of 14 wks.169 patients included (48%males, mean age 39 +/- 12 yrs). 64% of them had perianal disease. 82% were under immunosuppressants. 1,355 infliximab infusions administered (mean 8, range 1-30). 90% response rate and 48% remission rate were obtained with induction therapy. 73% followed maintenance treatment, and 78% of them maintained or improved the response after a mean follow up of 28 months (range 3.5-86). 24 patients lost response during the follow up, after a mean of 41 wks (range 6-248). Only the prescription of maintenance therapy was predictive factor for favourable response (p0.01). 17 infusion reactions were reported (10% of the patients, 1.2% of the infusions; only one case was severe) and were the cause of treatment withdrawal in 7 patients. Co-treatment with immunosuppressive drugs and maintenance infliximab therapy were protective factors for infusion reactions (p0.05). Other adverse events occurred in 26% of the patients, and were cause of treatment withdrawal in 7 patients.Infliximab is effective and safe for CD management but concomitant immunosuppressive drugs and maintenance treatment should be prescribed to obtain the best outcome. That confirms in a real life clinical setting the favourable results obtained in randomized clinical trials.

Background: The aim of the study was to evaluate the incidence of abnormality of liver tests (LTs) or hepatotoxicity in a large group of inflammatory bowel disease (IBD) patients and, specifically, to assess the incidence of azathioprine (AZA) / mercaptopurine (MP)-induced liver injury in a long-term follow-up study. Methods: All consecutive IBD patients followed for at least 5 years were included in this retrospective study. LTs including alanine transaminase, aspartate transaminase, alkaline phosphatase, γ-glutamyl transferase, and bilirubin were periodically monitored. “Abnormality-of-LTs” was defined as LTs between N (upper limit of the normal range) and 2 N, and “liver injury/hepatotoxicity” as LTs >2 N. Results: A total of 786 patients were included, and 138 received AZA/MP; 120 patients (15%) and 39 (5%) presented abnormality of LTs or hepatotoxicity, respectively, during follow-up. The most frequent explanations were AZA/MP treatment and fatty liver disease. Among AZA/MP-treated patients (690 patient-years follow-up) the incidence of abnormal LTs and hepatotoxicity was, respectively, 7.1% and 2.6% per patient-year. Most patients spontaneously normalized LTs despite maintaining AZA/MP. These drugs were withdrawn due to hepatotoxicity (LTs >5 N and lack of decrease despite 50% dose reduction) in 3.6% of the patients and all of them normalized LTs. Conclusions: In IBD patients, AZA or MP treatment induces abnormality of LTs in a relatively high proportion of the cases, but the development of true hepatotoxicity/liver injury is exceptional. Moreover, most of the cases of thiopurine-induced hepatotoxicity in IBD patients are mild, and the abnormalities in LTs spontaneously return to normal values despite AZA/MP being maintained, therapy withdrawal being necessary in only ≈4% of the patients. (Inflamm Bowel Dis)

The mean prevalence of azathioprine (AZA) or 6-mercaptopurine (MP)-induced liver injury in patients with inflammatory bowel disease was approximately 3%, and the mean annual drug-induced liver disorder rate was only 1.4%. However, this low figure calculated from retrospective studies contrasts with a much higher incidence (10%) reported by a prospective study. Thiopurine-induced hepatotoxicity can be grouped into three syndromes: hypersensitivity, idiosyncratic cholestatic reaction, and endothelial cell injury (with resultant raised portal pressures, veno-occlusive disease, or peliosis hepatis). A small percentage of patients present with a slight elevation of liver tests (LTs) that do not have clinical implications and LTs return to normal values during the follow-up, indicating that it is not always necessary to adjust the dose of the immunomodulator. However, when abnormalities in LTs are more marked, the dose of AZA/MP may be reduced 50%, with posterior clinical and analytical controls. With this strategy, LTs frequently normalize spontaneously, and the initial AZA/MP dose may be cautiously prescribed again. Thiopurines may induce an unusual severe cholestatic jaundice that may not regress but even progress despite thiopurine withdrawal. Therefore, these drugs should be completely withdrawn, and not only tapered, in those patients presenting clinically significant jaundice. Despite a lack of evidence that monitoring of LTs is necessary in patients receiving AZA/MP, routinely performed laboratory controls including LTs seem recommendable. However, the optimal monitoring schedule remains to be established. As long-term hepatotoxicity seems to be an unpredictable and potentially severe adverse drug reaction of 6-thioguanine, this drug should not be administered outside a clinical trial setting. (Am J Gastroenterol 2007;102:1518-527).

Nephrotoxicity has been described in some patients with inflammatory bowel disease (IBD) treated with 5-aminosalicylic acid (5-ASA). Studies with 5-ASA treatment in which serum creatinine or creatinine clearance was measured regularly show that nephrotoxicity is exceptional (mean rate of only 0.26% per patient-year). There have been several case reports, including 46 patients, of renal disease associated with 5-ASA treatment in patients with IBD. 5-ASA treatment-related nephrotoxicity is reported most often within the first 12 months, but also delayed presentation after several years has been shown. The absence of a clear relationship between 5-ASA dose and the risk of nephrotoxicity suggests that this complication is idiosyncratic rather than dose-related. Most of the patients with renal disease associated with 5-ASA treatment suffered interstitial nephritis, with symptoms and signs being nonspecific, which may delay detection for many months. The nephrotoxicity potential of mesalazine and sulfasalazine seems to be similar. The risk with different oral preparations of 5-ASA is probably too small to influence the choice of agent. Mesalazine should be withdrawn when renal impairment manifests in a patient with IBD; if this does not result in a fall in serum creatinine, then renal biopsy should be considered. A trial of high-dose steroid may be recommended in patients whose renal function does not respond to drug withdrawal. The optimal monitoring schedule of serum creatinine in patients receiving 5-ASA treatment remains to be established, as there is no evidence to date that either the test, or the frequency of testing, improves patient outcomes.

The role played by the distinct biological markers in chronic inflammatory bowel disease (IBD) remains insufficiently characterized. C-reactive protein (CRP) has a short half-life and consequently it is elevated early after the onset of the inflammatory process and rapidly decreases after its resolution, making it an attractive marker of disease activity. Moreover, this test is inexpensive and easy to perform and is unaffected by medication. While Crohn's disease is associated with a marked CRP response, there is little or no elevation in the synthesis of this protein in ulcerative colitis. Erythrocyte sedimentation rate provides some advantages such as its ease of determination, availability, and reduced cost. Nevertheless, it also has several disadvantages, notably the fact that its concentration depends on age, the presence of anemia, smoking, and the use of certain drugs. Moreover, its utility is limited by its long half life and consequent prolonged latency period after changes in chronic IBD activity. In theory, fecal markers have the advantages of showing greater specificity in the diagnosis of chronic IBD. Several gastrointestinal diseases, including chronic IBD, show greater leukocyte elimination in feces and a close correlation has been described between fecal calprotectin concentration and leukocyte excretion quantified by 111indium. Advantages of this fecal marker are that it can be detected through a simple and inexpensive technique and also shows excellent stability in feces for prolonged periods. Like calprotectin, fecal lactoferrin is also quantified by a simple and inexpensive ELISA method, although there is considerably less experience with this latter marker.

Introduction: Early stages of Crohn’s disease [CD] are predominantly inflammatory and early treatment could be useful to change the natural history of CD. We aimed to evaluate the impact of early treatment in our cohort of CD patients. Methods: We retrospectively reviewed clinical records of all CD patients at our centre who have received immunomodulators. Time from diagnosis to first CD-related major abdominal surgery or end of follow-up was considered. Dates of diagnosis, of starting immunomodulators (thiopurines / anti-tumour necrosis factor [TNF]), and of the first CD-related surgery when appropriate were collected. Results: Of 422 patients who received thiopurines, 189 operated patients started thiopurines after a median of 117 months (interquartile range [IQR] 44–196) since diagnosis; non-operated patients, after a median of 30 months [IQR 6–128], p < 0,005. Odds ratio [OR] for surgery was 1.006 (95% confidence interval [CI]1.004–1008) for each month of delay in starting thiopurines. Among 272 patients who received anti-TNFs, 137 operated patients started anti-TNFs after a median of 166 months [IQR 90–233] since diagnosis; non-operated patients after a median of 59 months [IQR 14–162]; p < 0,005. OR for surgery was 1.008 [95% CI 1.005–1.010] for each month of delay in starting anti-TNFs. Among 467 patients who received thiopurines and/or anti-TNF, 210 operated patients started any immunomodulator after a median of 120 months [IQR 48–197] since diagnosis and non-operated patients after a median of 30 months [IQR 6–126], p < 0,005. OR for surgery was 1.008 [95% CI 1.005–1.010] for each month of delay in starting immunomodulators. Conclusions: In our experience, time between diagnosis and thiopurine or anti-TNF initiation was associated with the risk of major abdominal surgery in Crohn’s disease.

Background: Current guidelines address the initiation of treatment to prevent postoperative recurrence (PR) after ileo-cecal resection in Crohn’s disease (CD), but appropriate management of postoperative CD patients who are already receiving treatment to prevent PR is yet to be defined. Usefulness of endoscopic monitoring in this scenario remains uncertain. Aims: To evaluate the usefulness of endoscopy-based management of postoperative CD patients who are already under pharmacological prevention of PR. Methods: Retrospective review of clinical outcome of all CD patients with ileo-cecal resection who underwent postoperative colonoscopy between 2004 and 2013 at our centre. Postoperative endoscopic findings were classified as no endoscopic recurrence (Rutgeerts i0-i1) or endoscopic recurrence (Rutgeerts i2-i4). Patients with endoscopic recurrence were classified as “endoscopy-based management (EBM)” if treatment step-up after endoscopy, or “non EBM (N-EBM)”. Clinical recurrence was considered if re-operation, CD related hospitalization or treatment change. Time until clinical recurrence or the end of the follow up was considered. Results: One hundred sixty six patients initially identified. One hundred twenty nine (77%) under pharmacological prevention of PR at the time of colonoscopy were analyzed: 34% were receiving aminosalicylates, 50% thiopurines, 11% anti-TNF, 5% combo. Colonoscopy showed endoscopic recurrence in 57% of patients; those with N-EBM were more likely to have clinical recurrence than patients with EBM along the follow up (p = 0.01). Conclussions: Endoscopic monitoring could be useful in postoperative CD patients also in patients already receiving pharmacological treatment to prevent PR.

espanolIntroduccion: entre los efectos adversos hepaticos secundarios al tratamiento tiopurinico en pacientes con enfermedad inflamatoria intestinal (EII), se ha descrito la posibilidad de desarrollar hipertension portal idiopatica. Esta patologia de etiologia y prevalencia real inciertas puede comprometer el pronostico de estos pacientes, por lo que se debe tener un alto grado de sospecha para su diagnostico precoz. Material y metodos: se ha llevado a cabo un estudio transversal en una cohorte de pacientes con EII en seguimiento en nuestra unidad para determinar la prevalencia del diagnostico de HTP idiopatica (HTPI) y su relacion con el tratamiento tiopurinico. Resultados: en nuestro centro, en el momento del analisis habia 1.419 pacientes en seguimiento por enfermedad inflamatoria intestinal. De estos, 927 pacientes se encuentran bajo tratamiento con farmacos tiopurinicos (o lo han estado durante la evolucion de su enfermedad), lo que supone el 65,3% de la poblacion: 689 pacientes con azatioprina (74,3%) y 238 con 6-mercaptopurina (25,7%). En total, se identificaron 4 pacientes con EII tipo enfermedad de Crohn con hipertension portal idiopatica en probable relacion con el tratamiento tiopurinico, lo que supuso un 4,3% del total, es decir, una incidencia de 4,3 casos por cada 1.000 pacientes con EII tratados con tiopurinicos. Las caracteristicas basales de los pacientes se describen en la tabla I. El 75% de los pacientes debuto con signos o sintomas de hipertension portal: 1 paciente con encefalopatia hepatica y 2 pacientes con hemorragia digestiva por varices esofagicas. Solo un paciente se encontraba asintomatico, pero se sospecho el diagnostico de HTP por trombopenia aislada. No obstante, cabe destacar que todos los pacientes presentaban trombopenia previamente aunque no se habia sospechado el diagnostico de HTP a pesar de un exhaustivo estudio. A todos los se realizo ecografia abdominal con fibroscan, cateterismo de venas suprahepaticas, asi como biopsia hepatica como parte del estudio etiologico de hipertension portal. En la ecografia abdominal se objetivaron datos indirectos de HTP en todos los pacientes (como esplenomegalia), descartandose asimismo cirrosis hepatica. El fibroscan mostraba datos de fibrosis hepatica significativa (F2-F3). Ademas, a todos los pacientes se les realizo una angiorresonancia en la que se descarto trombosis del eje esplenoportal como causa de HTP. Por ultimo, la anatomia patologica de la biopsia hepatica descarto la presencia de cirrosis hepatica, apoyando el diagnostico de HTP idiopatica (Tabla II). Conclusiones: la hipertension portal idiopatica secundaria a tratamiento tiopurinico en pacientes con enfermedad inflamatoria intestinal es un fenomeno poco frecuente, pero ha de ser tenido en cuenta en el diagnostico diferencial para un diagnostico precoz, principalmente en pacientes con tratamiento tiopurinico de larga evolucion. La presencia de trombopenia es a menudo el unico factor predictor de su desarrollo en fases preclinicas. EnglishIntroduction: The possibility of developing idiopathic portal hypertension has been described with thiopurine treatment despite compromises the prognosis of these patients, the fact its true prevalence is unknown. Material and methods: A cross-sectional study was conducted in a cohort of inflammatory bowel disease (IBD) patients followed at our unit, to determine the prevalence of diagnosis of idiopathic portal hypertension (IPH) and its relationship with thiopurine treatment. Results: At the time of the analysis, 927/1,419 patients were under treatment with thiopurine drugs (65%). A total of 4 patients with IBD type Crohn’s disease with idiopathic portal hypertension probably related to the thiopurine treatment were identified (incidence of 4.3 cases per 1,000). Seventy-five percent of patients started with signs or symptoms of portal hypertension. Only one patient was asymptomatic but the diagnosis of IPH because of isolated thrombocytopenia is suspected. However, note that all patients had thrombocytopenia previously. Abdominal ultrasound with fibroscan, hepatic vein catheterization and liver biopsy were performed on all of them as part of the etiology of portal hypertension. In the abdominal ultrasound, indirect portal hypertension data were observed in all patients (as splenomegaly) cirrhosis was also ruled out. The fibroscan data showed significant liver fibrosis (F2-F3). Conclusion: Idiopathic portal hypertension following thiopurine treatment in IBD patients is a rare occurrence, but it must be borne in mind in the differential diagnosis for early diagnosis, especially in patients undergoing thiopurine treatment over a long period. The presence of thrombocytopenia is often the only predictor of its development in the preclinical stage.

Summary Aim To perform a systematic review and meta-analysis on the efficacy and tolerance of infliximab in ulcerative colitis. Methods Selection of studies: evaluating efficacy of infliximab in ulcerative colitis. For the meta-analysis, randomized clinical trials comparing infliximab vs. placebo/steroids. Search strategy: electronic and manual. Study quality: independently assessed by two reviewers. Data synthesis: meta-analysis combining the odds ratios (OR). Results Thirty-four studies (896 patients) evaluated infliximab therapy in UC, with heterogeneous results. Mean short-term (2.3 weeks) response and remission with infliximab was 68% (95% CI 65–71%) and 40% (36–44%). Mean long-term (8.9 months) response and remission was 53% (49–56%) and 39% (35–42%). Five randomized double-blind studies compared infliximab with placebo, the meta-analysis showing an advantage (P

Determination of the activity of thiopurine methyltransferase (TPMT) and of thiopurine metabolites (6-thioguanine and 6-methylmercaptopurine nucleotides) could be useful for individualized monitoring of azathioprine (AZA) and 6-mercaptopurine (6-MP) doses. TPMT activity in the general population follows a trimodal distribution, in which approximately 0.3% of the population is homozygotic for the low-activity allele. A notable correlation has been observed between the low TPMP activity genotype or phenotype and the risk of myelotoxicity. Patients with a high TPMT activity genotype or homozygous phenotype should receive immunosuppressive doses that have clearly been demonstrated to be effective. In contrast, in patients with a low TPMT activity genotype or homozygous phenotype, the use of AZA/6-MP should be contraindicated or only very small doses should be administered. Importantly, TPMP deficiency explains only some cases of myelotoxicity and consequently periodic laboratory testing should be performed in patients receiving AZA/6-MP, even though TPMP function may be normal. Currently, the utility of routine thiopurine metabolite determinations in patients undergoing AZA/6-MP therapy has not been established and this practice should be limited to specific situations such as lack of response to thiopurine therapy or the occurrence of thiopurine-related adverse effects. Randomized trials comparing the routine strategy of AZA/6-MP dosing (based exclusively on the patient's weight) versus individualized monitoring (based on quantification of TPMP activity and/or thiopurine metabolites) are required before definitive conclusions on the most effective alternative can be drawn.

Resumen Introduccion Presentamos nuestra experiencia en el tratamiento endoscopico del diverticulo de Zenker. Pacientes y metodo Tres pacientes con diverticulos de Zenker de tamano medio fueron sometidos a una cricofaringomiotomia endoscopica realizada con un esfinterotomo de aguja modificado a traves de un gastroscopio terapeutico. El procedimiento se realize en la unidad de endoscopia digestiva bajo sedacion consciente sin apoyo anestesico. Resultado La cricofaringomiotomia endoscopica se completo en una unica sesion sin complicaciones inmediatas ni tardias. En los 3 pacientes desaparecio completamente la disfagia y todos fueron dados de alta a las 48 h con indicacion de dieta solida. Tras 12,18 y 17 meses de seguimiento no ha reaparecido la disfagia ni otros sintomas atribuibles al diverticulode Zenker. Conclusion La cricofaringomiotomia mediante endoscopio flexible es un tratamiento simple, eficaz y seguro del diverticulo de Zenker que ahorra la cirugia abierta cervical y la anestesia general.

Fundamento y objetivo El objetivo del presente estudio es describir la actividad enzimatica de la tiopurina metiltransferasa (TPMT) en un grupo muy numeroso de pacientes espanoles con enfermedad inflamatoria intestinal (EII), evaluar el efecto de algunas variables sobre dicha actividad y conocer la proporcion de pacientes con baja actividad y, por tanto, mayor riesgo de mielotoxicidad por azatioprina/6-mercaptopurina. Pacientes y metodo Se determino la actividad de TPMT mediante un metodo radioquimico en pacientes con EII. La asociacion entre diversas variables y la actividad de TPMT se estudio mediante regresion lineal multiple. Resultados Se incluyo a 7.046 pacientes, el 70% con enfermedad de Crohn, el 22% con colitis ulcerosa y un 8% con colitis indeterminada. El valor medio de TPMT fue de 20 U/ml (extremos: 0-46). La distribucion de actividad de TPMT fue: un 0,5% con valores bajos ( Conclusiones El 0,5% de los pacientes espanoles con EII tiene una baja actividad enzimatica de TPMT (

To the Editor: An increased risk of developing tuberculosis [TB] during anti-tumour necrosis factor [anti-TNF] therapy is well known. It is recommended to investigate the presence of latent tuberculosis infection [LTBI] or active TB before initiating biological therapy. We present a patient with LTBI who developed active TB despite having adopted correct preventive measures. A 45-year-old man with steroid-dependent ulcerative colitis was considered for a biological agent. Following current recommendations, screening for active and latent TB before anti-TNF was performed. A two-step tuberculin skin test was negative, but a chest X-ray image showed subcentimetric calcification, consistent with old …

Dear Sir, Opportunistic infections in patients with inflammatory bowel disease are gaining interest because of the new biologic therapies. We present the case of a Caucasian 53-year-old man with an extensive and steroid-dependent ulcerative colitis diagnosed 3 years ago. He had been previously been diagnosed (10 years ago) with mild chronic obstructive pulmonary disease, bronchiectasis and Hodgkin’s lymphoma (for which he received chemotherapy and is currently in remission). Because of his history of Hodgkin’s lymphoma, he wasn’t a suitable candidate to be treated with thiopurines; hence, he received treatment with oral mesalazine and granulocytapheresis in induction and maintenance dose, with loss of response. In …