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No studies evaluating the rapidity of response to biological therapies are available for Crohn's disease (CD). The aim of this study was to evaluate rapidity of onset of clinical response and impact on quality of life (QoL) of adalimumab therapy in adult anti-TNF-naïve patients with moderately-to-severely active CD.RAPIDA was an open-label, single-arm, prospective, multicenter clinical trial. Adult patients with moderately-to-severely active luminal CD, anti-TNF-naïve, and unresponsive to conventional therapy were treated with adalimumab. Clinical disease activity, QoL and inflammatory biomarkers were measured at day 4, and weeks 1, 2, 4, and 12 after treatment initiation.Eighty-six patients were included in the intention-to-treat (ITT) analyses. Clinical disease activity was reduced from a median of 9.0 points to 6.0 points at day 4. Clinical response (≥ 3-point reduction in the Harvey-Bradshaw Index, HBI) was achieved by 61.6% (d4) and 75.6% (w1) of patients in the ITT population (median 2.5 days) and with non-responder imputation (NRI), by 55.8% and 53.4%, respectively. The proportion of patients in clinical remission (HBI5) at weeks 2 and 4 in the ITT population was 54.7% and 62.8%, respectively (median 7.0 days), and 38.4% and 45.3% in the NRI population. All QoL scores significantly improved and inflammatory biomarkers significantly decreased from day 4 onwards (p0.0001).Rapid clinical response and remission, improvement in QoL and fatigue, and a reduction of inflammatory biomarkers were achieved with adalimumab as early as day 4 in adult anti-TNF-naïve patients with moderately-to-severely active CD.

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

Introduction A substantial proportion of adult patients with celiac disease on a gluten-free diet exhibit persistent villous atrophy, and inadvertent gluten exposure may be one of the causes. The aim of the present study was to evaluate villous atrophy persistence after 2 years on a gluten-free diet in de novo adult patients with celiac disease with strict control of gluten exposure. Methods Symptomatic de novo adult patients with celiac disease were prospectively included. Clinical visits and dietary surveillance were scheduled every 6 months during a 2-year follow-up period. At each visit, fecal samples were collected and stored at -20 °C until analysis for gluten immunogenic peptides (f-GIPs). A follow-up duodenal biopsy was performed at 2 years. We evaluated the variables associated with persistent villous atrophy. Results Seventy-six patients completed the study (36.5 ± 1.6 years, 73% women); persistent villous atrophy was observed in 40 (53%), whereas 72.5% were asymptomatic and 75% had negative serology. Detectable f-GIP >0.08 μg/g in at least 1 fecal sample was seen in 69% of patients. There were no significant differences in the median f-GIP at each visit and median area under the curve over the serial measurements between patients with persistent villous atrophy and those who recovered. On multivariate analysis, only older age was associated with persistent villous atrophy (32% for 16-30 years; 67% for >30 years; P = 0.016). Discussion The rate of persistent villous atrophy after 2 years was high in adult patients with celiac disease on an intentionally strict gluten-free diet. Low-level ongoing inadvertent gluten exposure could be a contributing factor to persistent villous atrophy.

The ENEIDA registry, promoted by the Spanish Working Group on Crohn's Disease and Ulcerative Colitis (GETECCU), was created in 2005 by a group of gastroenterologists interested in improving the management of patients with inflammatory bowel disease. The main objectives of the registry were to facilitate the collection of clinical data of interest for clinical care practice, as well as to carry out collaborative studies using clinical data and biological samples. In its 15 years of existence, ENEIDA has evolved in many aspects, from its content or technological support to the number of participating centres, to become one of the reference registries for the study and care of patients with inflammatory bowel disease, with a continuous and high quality scientific production that has positioned it as an example of collaborative scientific exploitation at an international level. This article reviews the objectives, design, structural characteristics, monitoring and scientific exploitation of the ENEIDA registry. (C) 2020 The Author(s). Published by Elsevier Espana, S.L.U.

Resumen Objetivos El objetivo de este trabajo fue evaluar el efecto de la vacunacion antigripal en la prevencion de casos graves asociados a gripe en pacientes adultos atendidos en un hospital de tercer nivel durante la temporada epidemica 2017-2018. Metodologia Se realizo un analisis descriptivo con toda la poblacion de sujetos con gripe confirmada por laboratorio en la temporada 2017-2018. Se definio caso grave como el ingreso en unidades de criticos o muerte. El efecto de la vacuna en la poblacion adulta se determino mediante analisis de regresion logistica multivariante. Resultados Entre las semanas epidemiologicas 44/2017 y 19/2018, el laboratorio del hospital detecto 706 muestras positivas de virus influenza. De los 551 pacientes confirmados de 18 anos o mas, cuarenta y tres fueron ingresados en alguna de las unidades de criticos del hospital y 26 fallecieron durante el ingreso. El modelo multivariante explicativo mostro la vacunacion de la gripe durante la temporada de estudio como factor protector del desarrollo de gravedad [OR: 0,27 (0,11-0,65), p = 0,004], ajustada por edad [1,03 (1,01-1,06), p = 0,04], sexo, tipo de virus (H1N1-pdm09, H3N2 o B) y el estar clasificado como Paciente Cronico Complejo o Enfermedad Avanzada Cronica. Conclusiones La vacuna de la gripe se muestra como factor protector frente al desarrollo de complicaciones en una temporada en la que la vacuna no contiene el virus que mas ha circulado entre la poblacion. Se debe recomendar la vacuna antigripal con periodicidad anual a los grupos de riesgo establecidos por las autoridades sanitarias.

Background The causes of seronegative villous atrophy can be grouped as coeliac or noncoeliac related. There is no consensus on how to approach subjects with seronegative coeliac disease. Aim To evaluate the accuracy of both an increase in CD3+ T-cell receptor gamma delta+ (TCRγδ+ ) intraepithelial lymphocytes and coeliac lymphogram for the diagnosis of coeliac disease in patients with seronegative villous atrophy. Methods Sixty-seven consecutive patients with seronegative villous atrophy were included. Duodenal biopsies to assess TCRγδ+ and CD3- by flow cytometry were performed at the index endoscopy. Coeliac lymphogram was defined as an increase in TCRγδ+ plus a decrease in CD3- intraepithelial lymphocytes. Sensitivity, specificity and Fagan's nomogram were calculated. Results Coeliac disease was diagnosed in 37 patients and noncoeliac villous atrophy in 30. Coeliac patients were younger (39 ± 3 vs 55 ± 3 years; P = 0.001), more often showed HLA-DQ2/8 (97.6% vs 61%; P = 0.002) and had a more severe histology (61% vs 32% Marsh 3b-c; P = 0.055), as compared to noncoeliac ones. Coeliac lymphogram was associated with a sensitivity of 87% (CI, 73.7-95) and specificity of 96.7% (82.7-99.9), whereas evaluating only TCRγδ+ yielded a sensitivity of 91.3% (79.2-97.6) and specificity of 83.3% (65.3-94.3). Among patients with a pre-test coeliac disease probability of 30%, post-test probabilities were 92% and 5% for positive and negative coeliac lymphogram, and 70% and 4% for positive and negative TCRγδ+ . Conclusions Coeliac lymphogram was associated with a high level of diagnostic evidence either against or in favour of coeliac disease in patients with seronegative villous atrophy.

Resumen Aunque un elevado porcentaje de pacientes con colitis ulcerosa deberia recibir tratamiento topico por via rectal, los estudios de practica clinica han demostrado que este esta infrautilizado. El proposito de este articulo es el de responder a 10 preguntas concretas sobre que farmacos estan disponibles para uso topico, su forma de presentacion, formulacion y metodos de aplicacion, asi como cual de ellos es mas eficaz e idoneo en los distintos escenarios clinicos de la colitis ulcerosa. Asimismo, se evalua la posibilidad de combinar diferentes formulaciones y vias de administracion, y la utilidad en la fase de remision de la enfermedad. Por ultimo, se hacen una serie de recomendaciones para una mejor informacion de los pacientes acerca de una correcta aplicacion y administracion.

IntroductionBCG vaccination modulates immune responses to unrelated pathogens. This off-target effect could reduce the impact of emerging pathogens. As a readily available, inexpensive intervention that has a well-established safety profile, BCG is a good candidate for protecting healthcare workers (HCWs) and other vulnerable groups against COVID-19.Methods and analysisThis international multicentre phase III randomised controlled trial aims to determine if BCG vaccination reduces the incidence of symptomatic and severe COVID-19 at 6 months (co-primary outcomes) compared with no BCG vaccination. We plan to randomise 10 078 HCWs from Australia, The Netherlands, Spain, the UK and Brazil in a 1:1 ratio to BCG vaccination or no BCG (control group). The participants will be followed for 1 year with questionnaires and collection of blood samples. For any episode of illness, clinical details will be collected daily, and the participant will be tested for SARS-CoV-2 infection. The secondary objectives are to determine if BCG vaccination reduces the rate, incidence, and severity of any febrile or respiratory illness (including SARS-CoV-2), as well as work absenteeism. The safety of BCG vaccination in HCWs will also be evaluated. Immunological analyses will assess changes in the immune system following vaccination, and identify factors associated with susceptibility to or protection against SARS-CoV-2 and other infections.Ethics and disseminationEthical and governance approval will be obtained from participating sites. Results will be published in peer-reviewed open-access journals. The final cleaned and locked database will be deposited in a data sharing repository archiving system.Trial registrationClinicalTrials.gov NCT04327206

Background Information on the use of fecal markers in microscopic colitis screening is limited. Aim To evaluate the risk variables associated with a diagnosis of microscopic colitis including fecal calprotectin. Methods Patients submitted for a colonoscopy due to chronic watery diarrhea fulfilling criteria of functional disease were evaluated. Colonic mucosa was normal but mild erythema and edema was allowed. Fecal calprotectin was analyzed. A logistic regression was used to evaluate variables associated with both raised fecal calprotectin and a diagnosis of microscopic colitis. Results 94 patients were included, 30 were diagnosed with microscopic colitis and 64 made up the control group. Median calprotectin levels were 175 (IQR, 59–325) for the microscopic colitis and 28 (IQR, 16–111) for the control group (p 100 μg/g (AUC, 0.73), with 67% sensitivity and 75% specificity. The number of drugs used ≥3 (OR, 3.9; CI, 1.4–10.4) and microscopic colitis diagnosis (OR, 6; CI, 2.2–16.3) were associated with raised calprotectin levels. Age >60 years (OR, 3.8; CI, 1.4–10.1) and calprotectin levels (OR, 5.3; CI, 2–14.1) were associated with a risk of microscopic colitis. Conclusions Elevated fecal calprotectin concentrations are often seen in microscopic colitis, and may be helpful in the diagnosis of women over 60 with chronic watery diarrhea.

The production of antibodies to anti-tumor necrosis factor alpha (TNF) agents is one of the main causes of treatment failure in Crohn’s disease (CD). To date, however, the contribution of genetics to anti-TNF immunogenicity in CD is still unknown. The objective of the present study was to identify genetic variation associated with anti-TNF immunogenicity in CD. We performed a two-stage genome-wide association study in a cohort of 96 and 123 adalimumab-treated patients, respectively. In the discovery stage, we identified a genome-wide significant association between the CD96 locus and the production of antibodies to anti-TNF treatment (P = 1.88e–09). This association was validated in the replication stage (P

BACKGROUND Cohort studies comparing the characteristics of childhood-onset and adulthood-onset inflammatory bowel disease (IBD) in the biologics era are scarce. AIM To compare disease characteristics, the use of immunomodulators and biologic agents and the need for surgery between childhood- and adulthood-onset IBD. METHODS Inflammatory bowel disease patients from the ENEIDA registry diagnosed between 2007 and 2017 were included. The childhood-onset cohort comprised patients diagnosed at ≤16 years of age and the adulthood-onset cohort those diagnosed at >16 years. The cumulative incidences of immunosuppressive therapy, biologic therapy and surgery were estimated using Kaplan-Meier curves, compared by the log-rank test. Cox regression analysis was performed to identify potential predictive factors of treatment with immunosuppressants, biologic agents or surgery. RESULTS The adulthood-onset cohort comprised 21 200 patients out of 20 354 (96%) and the childhood-onset cohort 846 (4%). Median follow-up was 54 months in the childhood-onset cohort and 38 months in the adulthood-onset cohort (P

1. Background: The long-term effect of a gluten-free diet (GFD) on functional bowel disorders (FBDs) has been scarcely studied. The aim was to assess the effect of a GFD on FBD patients, and to assess the role of both the low-grade coeliac score and coeliac lymphogram in the probability of response to a GFD. 2. Methods: 116 adult patients with either predominant diarrhoea or abdominal bloating, fulfilling Rome IV criteria of FBD, were treated with a GFD. Duodenum biopsies were performed for both pathology studies and intraepithelial lymphocyte subpopulation patterns. Coeliac lymphogram was defined as an increase in TCRγδ+ cells plus a decrease in CD3− cells. A low-grade coeliac score &gt, 10 was considered positive. 3. Results: Sustained response to GFD was observed in 72 patients (62%) after a median of 21 months of follow-up, who presented more often with coeliac lymphogram (37.5 vs. 11.4%, p = 0.02) and a score &gt, 10 (32 vs. 11.4%, p = 0.027) compared to non-responders. The frequency of low-grade coeliac enteropathy was 19.8%. 4. Conclusion: A GFD is effective in the long-term treatment of patients with previously unexplained chronic watery diarrhoea- or bloating-predominant symptoms fulfilling the criteria of FBD. The response rate was much higher in the subgroup of patients defined by the presence of both a positive low-grade coeliac score and coeliac lymphogram.

Background and AimsVedolizumab is an anti-α4β7 antibody approved for the treatment of ulcerative colitis [UC]. Although it is assumed that vedolizumab blocks intestinal homing of lymphocytes, its effects on different intestinal cell populations are not fully stablished. In order to establish the unique mechanisms of action of vedolizumab in UC patients, we compared its effects to those induced by anti-tumour necrosis factor [TNF].MethodsPatients with active UC [endoscopic Mayo score >1] starting vedolizumab [n = 33] or anti-TNF [n = 45] and controls [n = 22] were included. Colon biopsies [at weeks 0, 14 and 46] and blood samples [at weeks 0, 2, 6, 14, 30 and 46] were used for cell phenotyping, transcriptional analysis [qPCR], and to measure receptor occupancy.ResultsVedolizumab, in contrast to anti-TNF, significantly reduced the proportion of α4β7+ cells within intestinal T subsets while preserving the percentage of α4β7+ plasma cells. The marked decrease in α4β7 did not change the percentage of colonic αEβ7+ cells [at 46 weeks]. Both vedolizumab and anti-TNF significantly downregulated inflammation-related genes in the colon of responders [Mayo score < 2]. Moreover, both treatments significantly decreased the percentage of intestinal, but not blood, total lymphocytes [T and plasma cells], as well as the proportion of α4β1+ cells within intestinal T lymphocytes.ConclusionsOur data show that while vedolizumab and anti-TNF block two unrelated targets, they induce remarkably similar effects. On the other hand, vedolizumab’s unique mechanism of action relies on blocking intestinal trafficking of α4β7 T cells, despite effectively binding to B and plasma cells that express α4β7.

International audience; BACKGROUND/AIMS: Few data on the evolution of endoscopic findings are available in patients with acute severe ulcerative colitis (ASUC). The aim of this study was to describe this evolution in a prospective cohort. METHODS: Patients admitted for a steroid-refractory ASUC and included in a randomized trial comparing infliximab and cyclosporine were eligible if they achieved steroid-free clinical remission at day 98. Flexible sigmoidoscopies were performed at baseline, days 7, 42 and 98. Ulcerative colitis endoscopic index of severity (UCEIS) and its sub-scores - vascular pattern, bleeding and ulceration/erosion - were post-hoc calculated. Global endoscopic remission was defined by a UCEIS of 0, and partial endoscopic remission by any UCEIS sub-score of 0. RESULTS: Among the 55 patients analyzed (29 infliximab and 26 cyclosporine), 49 (83%) had UCEIS >= 6 at baseline at baseline. Partial endoscopic remission rates were higher for bleeding than for vascular pattern and for ulcerations/erosions at day 7 (20% vs. 4% and 5% (n = 55); p

Background The diagnosis of coeliac disease (CD) in individuals that have started a gluten-free diet (GFD) without an adequate previous diagnostic work-out is a challenge. Several immunological assays such as IFN-γ ELISPOT have been developed to avoid the need of prolonged gluten challenge to induce the intestinal damage. We aimed to evaluate the diagnostic accuracy of activated gut-homing CD8+ and TCRγδ+ T cells in blood after a 3-day gluten challenge and to compare it with the performance of IFN-γ ELISPOT in a HLA-DQ2.5 subsample. Methods A total of 22 CD patients and 48 non-CD subjects, all of them following a GFD, underwent a 3-day 10-g gluten challenge. The percentage of two T cell subsets (CD8+ CD103+ β7hi CD38+/total CD8+ and TCRγδ+ CD103+ β7hi CD38+/total TCRγδ+) in fresh peripheral blood drawn baseline and 6 days after the challenge was determined by flow cytometry. IFN-γ ELISPOT assays were also performed in HLA-DQ2.5 participants. ROC curve analysis was used to assess the diagnostic performance of the CD8+ T cell response and IFN-γ ELISPOT. Results Significant differences between the percentage of the two studied subsets of CD8+ and TCRγδ+ cells at days 0 and 6 were found only when considering CD patients (p < 10−3 vs. non-CD subjects). Measuring activated CD8+ T cells provided accurate CD diagnosis with 95% specificity and 97% sensitivity, offering similar results than IFN-γ ELISPOT. Conclusions The results provide a highly accurate blood test for CD diagnosis in patients on a GFD of easy implementation in daily clinical practice.

Background and Aims The development programm UNIFI has shown promising results of ustekinumab in ulcerative colitis [UC] treatment which should be confirmed in clinical practice. We aimed to evaluate the durability, effectiveness, and safety of ustekinumab in UC in real life. Methods Patients included in the prospectively maintained ENEIDA registry, who received at least one intravenous dose of ustekinumab due to active UC [Partial Mayo Score [PMS]>2], were included. Clinical activity and effectiveness were defined based on PMS. Short-term response was assessed at Week 16. Results A total of 95 patients were included. At Week 16, 53% of patients had response [including 35% of patients in remission]. In the multivariate analysis, elevated serum C-reactive protein was the only variable significantly associated with lower likelihood of achieving remission. Remission was achieved in 39% and 33% of patients at Weeks 24 and 52, respectively; 36% of patients discontinued the treatment with ustekinumab during a median follow-up of 31 weeks. The probability of maintaining ustekinumab treatment was 87% at Week 16, 63% at Week 56, and 59% at Week 72; primary failure was the main reason for ustekinumab discontinuation. No variable was associated with risk of discontinuation. Three patients reported adverse events; one of them had a fatal severe SARS-CoV-2 infection. Conclusions Ustekinumab is effective in both the short and the long term in real life, even in a highly refractory cohort. Higher inflammatory burden at baseline correlated with lower probability of achieving remission. Safety was consistent with the known profile of ustekinumab.

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

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

Introduction Endoscopic ultrasound (EUS) is a more sensitive technique than transabdominal ultrasound for the diagnosis of gallstones. This greater sensitivity, especially in the diagnosis of microlithiasis/biliary sludge, facilitates the indication of cholecystectomy in patients with symptoms of probable biliary origin but may result in over-indication of this surgery. Objectives Evaluate the role of EUS in the diagnosis of minilithiasis/biliary sludge in patients with digestive symptoms of probable biliary origin by resolving the symptoms after cholecystectomy. Analyse factors related to the remission of symptoms following cholecystectomy. Patients and methods Retrospective, longitudinal, single-centre study based on a prospective database of 1.121 patients undergoing EUS. Seventy-four patients were identified as meeting inclusion-exclusion criteria (diagnosed with minilithiasis/sludge by EUS after presenting digestive symptoms of probable biliary origin without a history of complicated cholelithiasis). A telephone questionnaire for symptoms was conducted with cholecystectomized patients. Factors related to a good response were analysed with logistic regression analysis. Results Of the 74 patients, 50 were cholecystectomized (67.5%), mean age 49 years (SEM 2.26) (41 women). Seventy percent of patients (35/50) presented remission of symptoms with median follow-up 353.5 days (95% CI, 270–632.2). The only variable associated with remission of symptoms was the presence of typical biliary colic with an OR of 7.8 (95% CI, 1.8–34; p = 0.006). No complications associated with EUS were recorded. One patient (2%) suffered haemoperitoneum and 18% (9/50) suffered diarrhoea following cholecystectomy. Conclusions EUS is a very useful technique for the indication of cholecystectomy in patients with minilithiasis/sludge and typical symptoms of biliary colic.

Introduction Influenza vaccination rates in risk groups remain suboptimal. Evidence supporting a significant association between influenza vaccination and severe illness is limited. Methods We retrospectively analyzed the epidemiological characteristics of out- and inpatients with laboratory-confirmed influenza infection attended during the 2018–19 epidemic season. Influenza vaccination coverage by indication was analyzed. Logistic regression was used to compare the odds of vaccination between severe and non-severe influenza-positive patients. Severe cases were defined as presenting pneumonia, admission to critical care units and/or death. Results The overall vaccination coverage among influenza-positive patients was 30.4%. In subjects with ≥ 1 indication for vaccination, the vaccination coverage was 42.4%. By indication, coverage rates were: 52.5% in patients aged ≥ 59 years, 42.2% in obese patients, 29.2% in immunosuppressed subjects and 6.5% in pregnant women. In patients with underlying chronic diseases, a higher coverage was found in patients with cognitive impairment (77%), muscular dystrophy (63.6%) and renal disease (60.4%). The multivariate logistic regression model showed severe influenza-related illness was associated with a lack of influenza vaccination before seeking care during the 2018–2019 season [0.59 (95%CI 0.36–0.97); p = 0.038], older age [1.01 (95%CI 1.00–1.02); p = 0.009] and current or former smoking status [1.63 (95%CI 0.84–3.18) and 2.03 (95%CI 1.16–3.57); p = 0.031], adjusted by underlying disease. Conclusion Adjusting by age, smoking status and underlying disease, a moderate association between the influenza vaccine and severe laboratory-confirmed influenza-related illness was found in an epidemic season in which there was matching between the vaccine and circulating strains. Protection against complications, especially in older subjects and in those with underlying disease is postulated as one of the strengths of annual influenza vaccination. However, influenza vaccination is a pending issue in these groups, especially in pregnant women and obese people. To avoid suboptimal vaccination coverages, health professionals should recommend the seasonal influenza vaccination according to the annual instructions of the health authorities.

This is the peer reviewed version of the following article: Changes in the requirement for early surgery in inflammatory bowel disease in the era of biological agents. Journal of Gastroenterology and Hepatology (2020): 29 April, which has been published in final form at https://doi.org/10.1111/jgh.15084. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions, Biological therapies may be changing the natural history of inflammatory bowel diseases, reducing the need for surgical intervention. We aimed to assess whether the availability of anti‐TNF agents impacts the need for early surgery in Crohn's disease (CD) and ulcerative colitis (UC). Methods Retrospective, cohort study of patients diagnosed within a 6‐year period before and after the licensing of anti‐TNFs (1990‐1995 and 2007‐2012 for CD; 1995‐2000 and 2007‐2012 for UC) were identified in the ENEIDA Registry. Surgery‐free survival curves were compared between cohorts. Results A total of 7,370 CD patients (2,022 in Cohort 1 and 5,348 in Cohort 2) and 8,069 UC patients (2,938 in Cohort 1 and 5,131 in Cohort 2) were included. Immunosuppressants were used significantly earlier and more frequently in both CD and UC post‐biological cohorts. The cumulative probability of surgery was lower in CD following anti‐TNF approval (16% and 11%, 22% and 16%, and 29% and 19%, at 1, 3 and 5 years, respectively p

Background Personalized medicine requires finding relationships between variables that influence a patient’s phenotype and predicting an outcome. Sparse generalized canonical correlation analysis identifies relationships between different groups of variables. This method requires establishing a model of the expected interaction between those variables. Describing these interactions is challenging when the relationship is unknown or when there is no pre-established hypothesis. Thus, our aim was to develop a method to find the relationships between microbiome and host transcriptome data and the relevant clinical variables in a complex disease, such as Crohn’s disease. Results We present here a method to identify interactions based on canonical correlation analysis. We show that the model is the most important factor to identify relationships between blocks using a dataset of Crohn’s disease patients with longitudinal sampling. First the analysis was tested in two previously published datasets: a glioma and a Crohn’s disease and ulcerative colitis dataset where we describe how to select the optimum parameters. Using such parameters, we analyzed our Crohn’s disease data set. We selected the model with the highest inner average variance explained to identify relationships between transcriptome, gut microbiome and clinically relevant variables. Adding the clinically relevant variables improved the average variance explained by the model compared to multiple co-inertia analysis. Conclusions The methodology described herein provides a general framework for identifying interactions between sets of omic data and clinically relevant variables. Following this method, we found genes and microorganisms that were related to each other independently of the model, while others were specific to the model used. Thus, model selection proved crucial to finding the existing relationships in multi-omics datasets.

INTRODUCTION: To compare Engerix-B and Fendrix hepatitisBvirus for primo vaccination in inflammatory bowel disease (IBD). METHODS: Patients with IBD were randomized 1:1 to receive Engerix-B double dose or Fendrix single dose at months 0, 1, 2, and 6. Anti-HBs titers were measured 2 months after the third and fourth doses. Response to vaccination was defined as anti-HBs >= 100 UI/L. Anti-HBs titers were measured 2 months after the third and fourth doses and again at 6 and 12 months after the fourth dose. RESULTS: A total of 173 patients were randomized (54% received Engerix-B and 46% Fendrix). Overall, 45% of patients responded (anti-HBs >= 100 IU/L) after 3 doses and 71% after the fourth dose. The response rate after the fourth dose was 75% with Fendrix vs 68% with Engerix-B (P 5 0.3). Older age and treatment with steroids, immunomodulators, or anti-tumor necrosis factor were associated with a lower probability of response. However, the type of vaccine was not associated with the response. Anti-HBs titer negativization occurred in13% of patients after 6months and 20% after12months. Anti-HBs 100 IU/L after vaccination was the only factor associated with maintaining anti-HBs titers during follow-up. DISCUSSION: We could not demonstrate a higher response rate of Fendrix (single dose) over Engerix-B (double dose). A 4-dose schedule is more effective than a 3-dose regimen. Older age and treatment with immunomodulators or anti-tumor necrosis factors impaired the success. A high proportion of IBD patients with protective anti-HBs titers after vaccination loose them over time. The risk of losing protective anti-HBs titers is increased in patients achieving anti-HBs

Background Patients with inflammatory bowel disease (IBD) may present extraintestinal manifestations (EIMs) that affect the joints, skin, eyes, and hepatobiliary area, among others. Aims Our aim was to analyse the prevalence and characteristics of EIMs in patients with IBD and to identify the possible risk factors associated with the development of EIMs in the largest series published to date. Methods Observational, cross-sectional study including patients from the Spanish ENEIDA registry promoted by GETECCU. We retrospectively identified all cases of EIMs in the ENEIDA registry until January 2018. Results The study included 31,077 patients, 5779 of whom had at least one EIM (global prevalence 19%; 95% CI 18.2-19.0). Among the different types of EIMs, rheumatic manifestations had a prevalence of 13% (95% CI 12.9-13.7; 63% of EIMs), with a prevalence of 5% (95% CI 4.7-5.2) for mucocutaneous manifestations, 2.1% (95% CI 1.9-2.2) for ocular manifestations, and 0.7% (95% CI 0.6-0.8) for hepatobiliary manifestations. The multivariable analysis showed that the type of IBD (Crohn's disease,p < 0.001), gender (female,p < 0.001), the need for an immunomodulator (p < 0.001) or biologic drugs (p < 0.001), a previous family history of IBD (p < 0.001), and an extensive location of IBD (p < 0.001) were risk factors for the presence of EIMs. Conclusions One-fifth of patients with IBD may have associated EIMs, with rheumatic manifestations as the most frequent (> 60% of EIMs). Female patients with severe Crohn's disease represent the group with the highest risk of developing EIMs. These patients should therefore be specially monitored and referred to the corresponding specialist when suggestive symptoms appear.

Background The effectiveness of the switch to another anti–tumor necrosis factor (anti-TNF) agent is not known. The aim of this study was to analyze the effectiveness and safety of treatment with a second and third anti-TNF drug after intolerance to or failure of a previous anti-TNF agent in inflammatory bowel disease (IBD) patients. Methods We included patients diagnosed with IBD from the ENEIDA registry who received another anti-TNF after intolerance to or failure of a prior anti-TNF agent. Results A total of 1122 patients were included. In the short term, remission was achieved in 55% of the patients with the second anti-TNF. The incidence of loss of response was 19% per patient-year with the second anti-TNF. Combination therapy (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.8–3; P < 0.0001) and ulcerative colitis vs Crohn’s disease (HR, 1.6; 95% CI, 1.1–2.1; P = 0.005) were associated with a higher probability of loss of response. Fifteen percent of the patients had adverse events, and 10% had to discontinue the second anti-TNF. Of the 71 patients who received a third anti-TNF, 55% achieved remission. The incidence of loss of response was 22% per patient-year with a third anti-TNF. Adverse events occurred in 7 patients (11%), but only 1 stopped the drug. Conclusions Approximately half of the patients who received a second anti-TNF achieved remission; nevertheless, a significant proportion of them subsequently lost response. Combination therapy and type of IBD were associated with loss of response. Remission was achieved in almost 50% of patients who received a third anti-TNF; nevertheless, a significant proportion of them subsequently lost response.

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

Ferrer-Picón et al. show that in active IBD patients, tumor necrosis factor alpha affects the response of the intestinal epithelium to bacteria-derived butyrate. This observation raises questions about the beneficial effects of butyrate supplementation during active inflammation., Background Butyrate-producing gut bacteria are reduced in patients with active inflammatory bowel disease (IBD), supporting the hypothesis that butyrate supplementation may be beneficial in this setting. Nonetheless, earlier studies suggest that the oxidation of butyrate in IBD patients is altered. We propose that inflammation may decrease epithelial butyrate consumption. Methods Non-IBD controls and IBD patients were recruited for the study. Stool samples were used for short-chain fatty acid and bacterial butyryl CoA:acetate CoA-transferase quantification. Colonic biopsies and ex vivo differentiated epithelial organoids (d-EpOCs) treated with butyrate and/or tumor necrosis factor alpha (TNFα) were used for analyzing the expression of transporters MCT1 and ABCG2, metabolic enzyme ACADS, and butyrate receptor GPR43, and for butyrate metabolism and consumption assays. Results We observed that lower stool content of butyrate-producing bacteria in active IBD patients did not correlate with decreased butyrate concentrations. Indeed, the intestinal epithelial expression of MCT1, ABCG2, ACADS, and GPR43 was altered in active IBD patients. Nonetheless, d-EpOCs derived from IBD patients showed SLC16A1 (gene encoding for MCT1 protein), ABCG2, ACADS, and GPR43 expression levels comparable to controls. Moreover, IBD- and non-IBD-derived d-EpOCs responded similarly to butyrate, as assessed by transcriptional regulation. TNFα significantly altered SLC16A1, ABCG2, and GPR43 transcription in d-EpOCs, mimicking the expression profile observed in biopsies from active IBD patients and resulting in reduced butyrate consumption. Conclusions We provide evidence that the response to butyrate is not intrinsically altered in IBD patients. However, TNFα renders the epithelium less responsive to this metabolite, defeating the purpose of butyrate supplementation during active inflammation.

Although macrophages (Mϕ) maintain intestinal immune homoeostasis, there is not much available information about their subset composition, phenotype and function in the human setting. Human intestinal Mϕ (CD45+HLA-DR+CD14+CD64+) can be divided into subsets based on the expression of CD11c, CCR2 and CX3CR1. Monocyte-like cells can be identified as CD11chighCCR2+CX3CR1+ cells, a phenotype also shared by circulating CD14+ monocytes. On the contrary, their Mϕ-like tissue-resident counterparts display a CD11c−CCR2−CX3CR1− phenotype. CD11chigh monocyte-like cells produced IL-1β, both in resting conditions and after LPS stimulation, while CD11c− Mϕ-like cells produced IL-10. CD11chigh pro-inflammatory monocyte-like cells, but not the others, were increased in the inflamed colon from patients with inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis. Tolerogenic IL-10-producing CD11c− Mϕ-like cells were generated from monocytes following mucosal conditioning. Finally, the colonic mucosa recruited circulating CD14+ monocytes in a CCR2-dependent manner, being such capacity expanded in IBD. Mϕ subsets represent, therefore, transition stages from newly arrived pro-inflammatory monocyte-like cells (CD11chighCCR2+CX3CR1+) into tolerogenic tissue-resident (CD11c−CCR2−CX3CR1−) Mϕ-like cells as reflected by the mucosal capacity to recruit circulating monocytes and induce CD11c− Mϕ. The process is nevertheless dysregulated in IBD, where there is an increased migration and accumulation of pro-inflammatory CD11chigh monocyte-like cells.

Background COVID-19 vaccine hesitancy seems to be universal across countries and subgroups, and so are its determinants. We studied the willingness and factors associated with the decision to be vaccinated against COVID-19 in healthcare workers (HCW) in a Spanish tertiary hospital. Furthermore, we compared the percentage of willingness to vaccinate against COVID with actual vaccination rates among HCW in our hospital. Methods From December 21, 2020 to January 4, 2021, before initiation of the COVID-19 HCW vaccination campaign at Germans Trias i Pujol University Hospital (HUGTiP), an anonymous self-administered questionnaire was administered to HCW. Univariate and multivariate logistic regression of the association of variables with the outcome “intention to receive the COVID-19 vaccine as soon as possible” was conducted. Vaccination rates were extracted from the hospital information systems. Results Forty-four percent of HCW included in the study declared a willingness to be vaccinated against COVID-19 as soon as possible. This was associated with male sex [1.66 (95%CI 1.13–2.43); p = 0.009], older age [1.02 (95%CI 1.00–1.03); p = 0.014], belonging to the occupational groups “physician” or “other” [5.76 (95%CI 3.44–9.63) and 2.15 (95%CI 1.25–3.70); p Conclusions COVID-19 vaccination uptake was higher than previously estimated according to the stated intentions of HCW. Doubts and fears must be addressed, particularly in persons less inclined to be vaccinated: females, younger people and those not vaccinated against influenza in recent seasons. The study of barriers and strategies aimed at promoting COVID-19 vaccination must be adapted in relation to occupational groups’ attitudes, understanding their idiosyncrasies with respect to this and other vaccines.

Despite the availability of new, powerful drugs for Crohn's disease, a significant proportion of patients will undergo an intestinal resection to control the disease as it develops. In the absence of an effective preventative treatment, the appearance of new intestinal lesions after surgery for Crohn's disease is the norm; this is known as post-operative recurrence and may appear very early on, even a few weeks after the surgical resection. Furthermore, the drugs that are currently available for the prevention of post-operative recurrence have a limited effect; up to 50% of cases present recurrent Crohn's disease activity despite the preventative treatment, which may require further surgery with the consequent loss of intestinal function, leading some patients to suffer from short bowel syndrome as an irreversible complication. The management of Crohn's disease patients who undergo an intestinal resection should thus be geared towards prevention, early detection and, in the worst case scenario, the treatment of post-operative recurrence. This article reviews the natural history, diagnostic measures, monitoring, prevention and treatment of post-operative recurrence, and proposes recommendations based on existing knowledge.

Resumen Introduccion El Blastocystis hominis (B. hominis) es un protozoo comunmente encontrado en el tracto gastrointestinal. Existen dudas sobre su significado clinico. El metronidazol (MTZ) es el tratamiento aconsejado de primera linea. Material y metodos Se realizo una revision retrospectiva entre 2011 y 2012. Se seleccionaron de forma aleatoria 151 de 383 muestras positivas para B. hominis . Los criterios de inclusion fueron: clinica sugestiva, indicacion de tratamiento y realizacion de control microbiologico. Se realizo una revision sistematica de los estudios que evaluan el efecto de MTZ sobre la infestacion por B. hominis . Resultados Cuarenta y seis pacientes cumplian criterios de inclusion (el 64% eran mujeres; edad, 44,2 ± 2 anos). Se utilizo MTZ en 39 pacientes, de los cuales 31 obtuvieron respuesta clinica (79,5%) pero solo 15 respuesta microbiologica (48,4%). No se aprecio una relacion dosis-efecto. Veinte pacientes sin respuesta microbiologica inicial recibieron una segunda tanda de tratamiento (MTZ, cotrimoxazol, paramomicina, otros), con una respuesta microbiologica del 70%. De forma global, se consiguio la curacion de B. hominis en un 72% (IC95%: 57-83%). De 54 tratamientos asociados a respuesta clinica, se produjo respuesta microbiologica en 31 (57%); mientras que de los 12 que se siguieron de ausencia de respuesta clinica solo se observo la curacion microbiologica en 2 (17%) (p = 0,022). La tasa de erradicacion en la revision sistematica oscilo entre 0 y 100%. Conclusiones Parece existir relacion entre la respuesta clinica y microbiologica al tratamiento de B. hominis . En nuestro entorno geografico la respuesta microbiologica al tratamiento con MTZ es insuficiente. La revision sistematica muestra que la respuesta a MTZ es muy variable.

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

Background INFEII registry (ClinicalTrials.gov: NCT02904590) is a prospective study promoted by GETECCU to determine the incidence and risk factors of infection in an inception cohort of IBD patients. Despite preventive measures and recommendations of scientific societies, TB remains a problem in patients with IBD treated with immunosuppressants (IMM) and biologics. AIMS To asses: (1) the screening of TB performed at the time of inclusion of a patient in the INFEII registry, (2) the incidence of latent TB; and (3) compliance with national and European recommendations. Methods A longitudinal prospective study of incident cases with IBD, initiated in October 2016 and with a planned follow-up of 5 years. In September 2019, INFEII registry had 1241 patients from 28 centres throughout Spain. The study protocol determines the mandatory fulfilment of TB screening in every patient, leaving to the centre the freedom of decision on what procedures to perform. Guidelines recommend a mandatory study before starting immunosuppression, especially with biological treatment, using the combination of tuberculin skin test (TST) and interferon-gamma release assay (IGRA) or at least one TST with a booster test1,2. Results Of the 1241 patients 233 (19%) had no screening, 494 (40%) had one [TST 158, IGRA 299, thorax-X-ray 37], 288 (23%) two [TST + IGRA 87, IGRA + thorax-X-ray 130, TST + thorax-X-ray 30, TST + booster 41], 128 (10%) three [TST + IGRA + thorax-X-ray 65, TST + booster + IGRA 23, TST + booster + thorax-X-ray 40] and 98 (7.9%) the four tests [TST + booster + IGRA + thorax-X-ray]. 486 patients (48%) receive pharmacological immunosuppression (172 IMMS, 195 biologics, 119 COMBO) and from them 198 (41%) followed the guidelines recommendation (131 TST and IGRA and 118 TST-booster), 245 (50%) had some method for TB screening [TST 43, IGRA 112, thorax-X-ray 15, IGRA + thorax-X-ray 57, TST + thorax-X-ray 18] and 43 patients (8.8%) had no screening. With the baseline screening, latent TB was detected in 134 patients (13%), 63 (47%) receiving anti-TB chemotherapy. In patients initiating immunosuppression, latent TB was detected in 35 cases [of which 28 received prophylaxis but 7 under IMM did not]. Active TB was detected in 4 cases: 2 during baseline screening, one without screening and one with negative screening (negative TST and IGRA, without booster receiving biological treatment). Conclusion Despite TB in IBD is a relevant problem, there is ample room for improvement for the implementation of mandatory minimum screening recommendations, even in prospective protocolised projects. References

It has been suggested that in doubtful cases of coeliac disease, a high CD3+ T-cell receptor gamma delta+ (TCR&gamma, &delta, +) intraepithelial lymphocyte count increases the likelihood of coeliac disease. Aim: To evaluate the diagnostic accuracy of both an isolated increase of TCR&gamma, + cells and a coeliac lymphogram (increase of TCR&gamma, + plus decrease of CD3&minus, intraepithelial lymphocytes) evaluated by flow cytometry in the diagnosis of coeliac disease. Methods: The literature search was conducted in MEDLINE and EMBASE. The inclusion criteria were: an article that allows for the construction of a 2 &times, 2 table of true and false positive and true and false negative values. A diagnostic accuracy test meta-analysis was performed. Results: The search provided 49 relevant citations, of which 6 were selected for the analysis, which represented 519 patients and 440 controls. Coeliac lymphogram: The pooled S and Sp were 93% and 98%, without heterogeneity. The area under the SROC curve (AUC) was 0.98 (95% CI, 0.97&ndash, 0.99). TCR&gamma, +: Pooled S and Sp were both 95%, with significant heterogeneity. The AUC was 0.97 (95% CI, 0.95&ndash, 0.98). Conclusions: Both TCR&gamma, + count and coeliac lymphogram assessed by flow cytometry in duodenal mucosal samples are associated with a high level of diagnostic accuracy for and against coeliac disease.

Background Fatigue is a common symptom in patients with inflammatory bowel disease (IBD), and it often persists despite clinical remission. Acupuncture has been shown to be effective for treating fatigue in patients with many chronic diseases. The main objective of the study was to assess the efficacy of electroacupuncture (EAc), compared with sham EAc (ShEAc) or being on a waitlist (WL), for treating fatigue in patients with quiescent IBD in a single-blind randomized trial. Methods Fifty-two patients with IBD in clinical remission and fatigue were randomly assigned to 1 of 3 groups: EAc, ShEAc, or WL. Patients in the EAc and ShEAc groups received 9 sessions over 8 weeks. Fatigue was evaluated with the IBD-validated Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-FS). Results Baseline characteristics were similar in the 3 groups. Both EAc and ShEAc presented improved Functional Assessment of Chronic Illness Therapy-Fatigue Scale scores compared with baseline: the respective improvements were 9.53 (95% confidence intervals, 6.75–12.3, P < 0.001) and 5.46 points (95% confidence intervals, 2.7–9.7, P = 0.015), respectively. No significant changes were observed in the WL group. In the comparison of treatment groups, EAc was nonsignificantly better than ShEAc (EAc, 33.27 and ShEAc, 28.13, P = 0.168); both EAc and ShEAc improved fatigue scores significantly compared to WL (24.5; P = 0.01 and 0.04, respectively). Conclusions Both EAc and ShEAc reduced fatigue scores in IBD patients when compared to WL. No differences were observed between EAc and ShEAc, although the study was not powered to rule out a difference. Acupuncture may offer improvements to patients with few other treatment alternatives. Clinical Trials Org Id: NCT02733276.

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

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

Background: In APPRECIA trial, Crohn's disease (CD) patients undergoing intestinal resection were randomized to postoperative adalimumab (ADA) or azathioprine (AZA). Aims: To evaluate health-related quality of life (HRQoL) in APPRECIA trial. Methods: HRQoL was evaluated using disease-specific shortened Spanish version of the IBDQ (SIBDQ-9) and generic European Quality of Life-5 Dimensions (EQ-5D) questionnaires, completed at baseline and at weeks 24 and 52. Results: Sixty-one patients (37 ADA and 24 AZA) had evaluable data for HRQoL. Patients treated with ADA or AZA had significant improvement from baseline to weeks 24 and 52 in SIBDQ-9 and EQ-5D (p < 0.001 and p = 0.006 for all comparisons, respectively). There were no differences between treatment arms in mean change in SIBDQ-9 and EQ-5D at weeks 24 and 52 vs baseline. Only patients without endoscopic recurrence had significant improvement in SIBDQ-9 (p < 0.001) and EQ-5D (p < 0.001) at week 52. At week 52, there was a high to moderate negative correlation between CDAI score with SIBDQ-9 score( Pearson's r: -0.768) and with EQ-5D index (r: -0.644). Conclusion: HRQoL improved after intestinal resection in CD, irrespective of the postoperative therapyused (ADA or AZA). Outcomes in HRQoL were associated with prevention of endoscopic recurrence, sinceimprovements in HRQoL were only significant in patients with endoscopic remission at 1 year. (c) 2019 Editrice Gastroenterologica Italiana S. r. l. Published by Elsevier Ltd. All rights reserved.

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

Healthcare workers (HCW) are exposed to preventable infectious diseases, notably hepatitis B (HB). The aim of this study was to determine the immunity of HCW against hepatitis B. We made a seroprevalence study using a self-administered survey and obtained blood samples. Antibodies against the HB surface antigen (anti-HBs) and against the HB core antigen (anti-HBc) were studied. The odds ratio (OR) and 95% confidence intervals (CI) were calculated. The adjusted OR were calculated using logistic regression. Of the 644 HCW who participated (29.7% physicians, 38.7% nurses, 13.4% other clinical workers and 18.3% non-clinical workers), 46.4% were primary care workers and 53.6% hospital workers. The overall prevalence of anti-HBs was 64.4%. HCW aged25 y had a significantly higher prevalence (86.7%) than those aged 35-44 y (adjusted OR 3.40; 95% CI 1.06-10.90). The prevalence of anti-HBc was 4.1%, and increased with age. Significant differences were found for HCW aged44 y with respect to those aged 25-34 y. 75.6% of HCW stated they were vaccinated, but only 39.3% had a vaccination card. In HCW who stated they were unvaccinated, 10.8% had a vaccinated serological pattern (anti-HBc-negative and anti-HBs -positive). Written, updated vaccination records are essential to reliably determine the vaccination status.

Chronic diarrhoea is a common presenting symptom in both primary care medicine and in specialized gastroenterology clinics. It is estimated that >5% of the population has chronic diarrhoea and nearly 40% of these patients are older than 60 years. Clinicians often need to select the best diagnostic approach to these patients and choose between the multiple diagnostic tests available. In 2014 the Catalan Society of Gastroenterology formed a working group with the main objective of creating diagnostic algorithms based on clinical practice and to evaluate diagnostic tests and the scientific evidence available for their use. The GRADE system was used to classify scientific evidence and strength of recommendations. The consensus document contains 28 recommendations and 6 diagnostic algorithms. The document also describes criteria for referral from primary to specialized care.

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

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

Health Care Workers (HCW) may have an occupational risk of latent tuberculosis infection (LTBI) and TB disease. The objective of this study was to evaluate the performance of the 2-step strategy: tuberculin skin test (TST) followed by confirmation with Interferon (IFN)-γ- release assays (IGRAs) in HCW. A secondary objective was to determine the factors related to conversions and reversions. HCW at risk of occupational exposure who attended the Occupational Department of the Hospital Germans Trias i Pujol were included during the study period (2013-2016). All professionals testing negative for LTBI were included in a cohort study. These workers were followed up with the administration of a TST and an IGRA quantification at least one year after inclusion in the study. Workers with positive TST, regardless of the results of the IGRA tests, were followed-up with an IGRA. 255 workers were enrolled in the study and 108 workers from the same cohort were followed up. During the follow-up period, seven workers presented TST test conversion. One of these conversions was also confirmed by an IGRA test. There were 2 conversions of cases only testing positive with the IGRA. There have been only 2 reversions of cases testing negative with the IGRA. In this study, not all TST conversions were confirmed when using the IGRA test, which highlights the importance of the 2-step strategy. We have detected a low number of conversions and reversions. Our conclusions should be confirmed in studies with a longer follow-up time.

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

Background A limited number of small-sized studies suggest that bile acid diarrhoea is frequent in patients with chronic watery diarrhoea and previous cholecystectomy. Aim To perform a systematic review and meta-analysis to assess the prevalence of bile acid diarrhoea in patients with chronic watery diarrhoea and previous cholecystectomy, and their response to colestyramine, including a new consecutive series of patients. Methods MEDLINE and EMBASE were searched up to January 2018. Selected studies included patients with previous cholecystectomy and chronic watery diarrhoea assessed by the 23-seleno-25-homotaurocholic acid (SeHCAT) test. We calculated the pooled rate of bile acid diarrhoea using the inverse double arcsine square root method. Additionally, the medical records of 291 consecutive patients with chronic watery diarrhoea in whom a SeHCAT test was performed were retrospectively reviewed and 74 with previous cholecystectomy were included in the meta-analysis. Results The search strategy identified eight relevant studies, which, together with the data of the present series, comprise 361 individuals. The pooled bile acid diarrhoea rate was 70% (95% CI 56%-82%), and was similar when using cut-offs of 10% or 15%. There was substantial heterogeneity (I2 = 84%). Five studies comprising 166 patients evaluated the effect of colestyramine in patients with bile acid diarrhoea. The pooled colestyramine response rate was 79% (95% CI 63%-91%) with substantial heterogeneity (I2 = 73%). Conclusions Two-thirds of patients with chronic watery diarrhoea and previous cholecystectomy have bile acid diarrhoea. Response to colestyramine in these patients is good.

Actualmente, el manejo de la enfermedad inflamatoria intestinal (EII) se basa en la evaluación objetiva de las lesiones intestinales. Por ello, es de interés disponer de herramientas sencillas y no invasivas con las que monitorizar la actividad de la EII e identificar la presencia de lesiones. La calprotectina fecal (CF) constituye la principal proteína citosólica de los neutrófilos, es resistente a la degradación bacteriana y estable a temperatura ambiente durante días, características que la hacen adecuada para su uso en la práctica clínica. Es útil para diferenciar entre procesos inflamatorios y funcionales, se correlaciona con la actividad endoscópica, se asocia con la respuesta clínica y endoscópica al tratamiento y tiene valor pronóstico a corto plazo. El presente documento pretende ofrecer una visión actualizada sobre la información que la CF puede proporcionar al clínico en el diagnóstico, la monitorización y el manejo de la EII.