Severe and refractory gastrointestinal toxicity due to immune checkpoint inhibitors: clinical experience in a tertiary referral hospital.

INTRODUCTION: immune checkpoint inhibitors (ICI) are increasingly used to treat several types of cancer. These drugs lead to a wide range of toxicities. Immune-related gastrointestinal adverse events are common and potentially severe. In this manuscript, we recount the real clinical experience in a tertiary center. METHODS: a retrospective and observational study was conducted in adult patients under ICI treatment. Included patients had been referred to the Gastrointestinal Service of Hospital Universitario Vall d'Hebron for evaluation of severe toxicities, from January 2017 to January 2020, for whom the clinical, epidemiological and evolutive data were collected. RESULTS: a total of 18 patients were included. Fifty-five percent received anti-programmed cell death protein 1 (PD-1)/anti-programmed death-ligand 1 (anti PD-L1), 11 % received anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) and 33 % received both treatments. The toxicities were manifested as enterocolitis, microscopic colitis and gastritis. Upper gastrointestinal endoscopy was performed in seven patients; all were proved to have histological changes on duodenum biopsies. Treatment was stopped in all patients and steroids were initiated. Sixty-six per cent achieved clinical remission with steroids. Five patients received anti-TNF treatment (infliximab). Only one of the five had responded. Two anti-TNF refractory patients received ustekinumab, with an appropriate clinical response. One patient received apheresis granulocyte as concomitant treatment. A patient with a steroid-dependent course started vedolizumab. Three patients had other immune-related adverse events. CONCLUSION: gastrointestinal immune-related adverse events are acquiring a higher profile in daily practice and gastroenterologists play an even greater role in the management of these patients.

Alterations in Gut Microbiome in Cirrhosis as Assessed by Quantitative Metagenomics: Relationship With Acute-on-Chronic Liver Failure and Prognosis.

BACKGROUND AND AIMS: Cirrhosis is associated with changes in gut microbiome composition. Although acute-on-chronic liver failure (ACLF) is the most severe clinical stage of cirrhosis, there is lack of information about gut microbiome alterations in ACLF using quantitative metagenomics. We investigated the gut microbiome in patients with cirrhosis encompassing the whole spectrum of disease (compensated, acutely decompensated without ACLF, and ACLF). A group of healthy subjects was used as control subjects. METHODS: Stool samples were collected prospectively in 182 patients with cirrhosis. DNA library construction and sequencing were performed using the Ion Proton Sequencer (ThermoFisher Scientific, Waltham, MA). Microbial genes were grouped into clusters, denoted as metagenomic species. RESULTS: Cirrhosis was associated with a remarkable reduction in gene and metagenomic species richness compared with healthy subjects. This loss of richness correlated with disease stages and was particularly marked in patients with ACLF and persisted after adjustment for antibiotic therapy. ACLF was associated with a significant increase of Enterococcus and Peptostreptococcus sp and a reduction of some autochthonous bacteria. Gut microbiome alterations correlated with model for end-stage liver disease and Child-Pugh scores and organ failure and was associated with some complications, particularly hepatic encephalopathy and infections. Interestingly, gut microbiome predicted 3-month survival with good stable predictors. Functional analysis showed that patients with cirrhosis had enriched pathways related to ethanol production, γ-aminobutyric acid metabolism, and endotoxin biosynthesis, among others. CONCLUSIONS: Cirrhosis is characterized by marked alterations in gut microbiome that parallel disease stages with maximal changes in ACLF. Altered gut microbiome was associated with complications of cirrhosis and survival. Gut microbiome may contribute to disease progression and poor prognosis. These results should be confirmed in future studies.

Intercontinental Gut Microbiome Variances in IBD.

The development of biomarkers for inflammatory bowel disease (IBD) diagnosis would be relevant in a generalized context. However, intercontinental investigation on these microbial biomarkers remains scarce. We examined taxonomic microbiome variations in IBD using published DNA shotgun metagenomic data. For this purpose, we used sequenced data from our previous Spanish Crohn's disease (CD) and ulcerative colitis (UC) cohort, downloaded sequence data from a Chinese CD cohort, and downloaded taxonomic and functional profiling tables from a USA CD and UC cohort. At the global level, geographical location and disease phenotype were the main explanatory covariates of microbiome variations. In healthy controls (HC) and UC, geography turned out to be the most important factor, while disease intestinal location was the most important one in CD. Disease severity correlated with lower alpha-diversity in UC but not in CD. Across geography, alpha-diversity was significantly different independently of health status, except for CD. Despite recruitment from different countries and with different disease severity scores, CD patients may harbor a very similar microbial taxonomic profile. Our study pointed out that geographic location, disease activity status, and other environmental factors are important contributing factors in microbiota changes in IBD. We therefore strongly recommend taking these factors into consideration for future IBD studies to obtain globally valid and reproducible biomarkers.

Normalization of long-term quality of life in Crohn's disease patients receiving ustekinumab.

BACKGROUND AND AIM: ustekinumab is a fully human monoclonal antibody against IL-12/23, approved for induction and maintenance treatment of Crohn's disease (CD). Real-life data shows its true effectiveness in terms of clinical and endoscopic response. However, there is little information regarding health-related quality of life (HRQoL) in CD patients receiving ustekinumab. The main aim of this study was to define long-term clinical remission and HRQoL normalization. The clinical predictive factors of clinical remission were investigated as a secondary aim. METHODS: a retrospective, observational study was performed in CD patients under ustekinumab treatment in the Hospital Vall d'Hebron, between January 2009 and January 2019. Clinical remission was defined using the Crohn's Disease Activity Index (CDAI) and HRQoL normalization was defined by the 36-item Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: thirty-three patients were included. The average disease evolution was eleven years (standard deviation [SD]: 8), perianal disease was present in 13 patients (39 %), 30 patients (91 %) had previously been treated with alfa tumor necrosis factor antagonists (anti-TNF) agents and 22 patients (67 %) had a history of intestinal resection. Twenty-four patients (73 %) had undergone one year of treatment. Seventeen patients (51 %) reached clinical remission and six (18 %) restored the HRQoL. No predictors of clinical remission were identified. CONCLUSIONS: ustekinumab shows clinical effectiveness in real-life conditions similar to previous data. Normalization of HRQoL is low compared to clinical remission, which may be due to the inaccuracy of the indicator and the severe disease course. Such normalization is a challenge for physicians dealing with inflammatory bowel diseases.

Impact of the COVID-19 pandemic on the activity of advanced-practice nurses on a reference unit for inflammatory bowel disease.

OBJECTIVE: To report the impact of the COVID-19 pandemic on the activity of nurses working on an inflammatory bowel disease (IBD) unit and to identify reasons for telehealth care and its relationship to certain characteristics. BACKGROUND: The COVID-19 pandemic had led to an increase in demand for remote care in patients with inflammatory bowel disease who require monitoring and frequent access to health services. DESIGN - METHODS: A retrospective study of all activity (in person and by phone call or email) done on the unit during the acute phase of the pandemic at a reference hospital in Spain. Numbers of activities done by nurses, reasons for telehealth care and sociodemographic and clinical data were collected. Statistical analysis was performed using frequency, chi-squared and analysis of variance tests. RESULTS: A total of 1095 activities for 561 patients who received care were reported. Among them, 1042 (95.2%) were telemedicine activities, amounting to a 47.3% increase over the prior year. COVID-19-related activities numbered 588 (59.5%). Consultations due to disease flare-up numbered 134 (13.7%), representing a 145% increase compared to 2019. Significant differences were found between reasons for using telemedicine and diagnosis, occupational status, contact week and treatment. CONCLUSION: The acute phase of the pandemic has changed the activity managed by the nursing staff on the unit. Identifying and analysing these changes has yielded valuable information to achieve more efficient management and better care quality for patients in special situations.

Multidisciplinary, evidence-based consensus guidelines for human papillomavirus (HPV) vaccination in high-risk populations, Spain, 2016.

INTRODUCTION: Although human papillomavirus (HPV) routine vaccination programmes have been implemented around the world and recommendations have been expanded to include other high-risk individuals, current recommendations often differ between countries in Europe, as well as worldwide. AIM: To find and summarise the best available evidence of HPV vaccination in high-risk patients aiding clinicians and public health workers in the day-to-day vaccine decisions relating to HPV in Spain. METHODS: We conducted a systematic review of the immunogenicity, safety and efficacy/effectiveness of HPV vaccination in high-risk populations between January 2006 and June 2016. HPV vaccination recommendations were established with levels of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: A strong recommendation about HPV vaccination was made in the following groups: HIV infected patients aged 9-26 years; men who have sex with men aged 9-26 years; women with precancerous cervical lesions; patients with congenital bone marrow failure syndrome; women who have received a solid organ transplant or hematopoietic stem cell transplantation aged 9-26 years; and patients diagnosed with recurrent respiratory papillomatosis. CONCLUSIONS: Data concerning non-routine HPV vaccination in populations with a high risk of HPV infection and associated lesions were scarce. We have developed a document to evaluate and establish evidence-based guidelines on HPV vaccination in high-risk populations in Spain, based on best available scientific evidence.

A microbial signature for Crohn's disease.

OBJECTIVE: A decade of microbiome studies has linked IBD to an alteration in the gut microbial community of genetically predisposed subjects. However, existing profiles of gut microbiome dysbiosis in adult IBD patients are inconsistent among published studies, and did not allow the identification of microbial signatures for CD and UC. Here, we aimed to compare the faecal microbiome of CD with patients having UC and with non-IBD subjects in a longitudinal study. DESIGN: We analysed a cohort of 2045 non-IBD and IBD faecal samples from four countries (Spain, Belgium, the UK and Germany), applied a 16S rRNA sequencing approach and analysed a total dataset of 115 million sequences. RESULTS: In the Spanish cohort, dysbiosis was found significantly greater in patients with CD than with UC, as shown by a more reduced diversity, a less stable microbial community and eight microbial groups were proposed as a specific microbial signature for CD. Tested against the whole cohort, the signature achieved an overall sensitivity of 80% and a specificity of 94%, 94%, 89% and 91% for the detection of CD versus healthy controls, patients with anorexia, IBS and UC, respectively. CONCLUSIONS: Although UC and CD share many epidemiologic, immunologic, therapeutic and clinical features, our results showed that they are two distinct subtypes of IBD at the microbiome level. For the first time, we are proposing microbiomarkers to discriminate between CD and non-CD independently of geographical regions.

Enterotypes of the human gut microbiome.

Our knowledge of species and functional composition of the human gut microbiome is rapidly increasing, but it is still based on very few cohorts and little is known about variation across the world. By combining 22 newly sequenced faecal metagenomes of individuals from four countries with previously published data sets, here we identify three robust clusters (referred to as enterotypes hereafter) that are not nation or continent specific. We also confirmed the enterotypes in two published, larger cohorts, indicating that intestinal microbiota variation is generally stratified, not continuous. This indicates further the existence of a limited number of well-balanced host-microbial symbiotic states that might respond differently to diet and drug intake. The enterotypes are mostly driven by species composition, but abundant molecular functions are not necessarily provided by abundant species, highlighting the importance of a functional analysis to understand microbial communities. Although individual host properties such as body mass index, age, or gender cannot explain the observed enterotypes, data-driven marker genes or functional modules can be identified for each of these host properties. For example, twelve genes significantly correlate with age and three functional modules with the body mass index, hinting at a diagnostic potential of microbial markers.

Predictive value of early restoration of quality of life in Crohn's disease patients receiving antitumor necrosis factor agents.

BACKGROUND AND AIM: Crohn's disease (CD) impairs patients' health-related quality of life (HRQoL), therefore a goal of treatment is to improve their health. Recently, a more ambitious therapeutic target has been proposed, to reestablish patients' HRQoL to normal standards. There is no information on long-term prognostic value of restoring the health of patients with CD. Our aim was to determine if early restoration of HRQoL with antitumor necrosis factor (anti-TNF) agents is associated with long-term clinical remission. METHODS: Retrospective longitudinal study in patients with active CD treated with anti-TNF agents. Patients completed the Inflammatory Bowel Disease Questionnaire (IBDQ)-36 at baseline and weeks 2, 6, 14, 28, and 52. Early restoration of health was defined as an IBDQ-36 score > 209 at week 14, and long-term clinical remission as a Cohn's disease activity index (CDAI) score < 150 maintained through week 52. RESULTS: Ninety-four patients were included. Sixty-three patients maintained long-term remission, with 47 (75%) of them achieving early restoration of HRQoL. Of the 31 patients who did not maintain long-term remission, only 4 (13%) restored their HRQoL early (P < 0.01). There was a strong negative correlation between the IBDQ-36 at week 14 and CDAI values at week 52 (rs = - 0.64, P < 0.01). Ninety-two percent of patients with early restoration of HRQoL maintained long-term remission versus 37% who did not restore their HRQoL (P < 0.01). To predict long-term remission, the cutoff point of 209 of the early IBDQ-36 had an area under the receiver operating characteristic (AUROC) curve of 0.87. CONCLUSION: Achieving early restoration of HRQoL with anti-TNF agents is associated with sustained long-term remission. This could be a therapeutic goal of treatment in clinical trials and daily practice.

Treatment preferences of patients with Crohn's disease: Development of the IMPLICA questionnaire.

INTRODUCTION AND OBJECTIVE: Patient preferences with respect to available therapies must be taken into account if the quality of care of patients with Crohn´s disease is to be improved. The objective was to develop the IMPLICA preferences questionnaire for Crohn´s disease patients treated with biological therapies. METHODS: As per standard methodology, the questionnaire was developed in Spanish language, in five stages: 1. Literature review to identify attributes related to biological therapies in Crohn´s disease; 2. Expert meeting to identify attributes most relevant for patients; 3. Scoring of the most relevant attributes and generation of scenarios; 4. Patient comprehension test for selection and validation of scenarios; and 5. Final list of scenarios and qualitative evaluation of those most accepted by patients. RESULTS: Three attributes related to various characteristics of biological treatments were selected: route of administration, place/duration of administration and person administering the treatment; a combination of them produced seven possible scenarios. The comprehension test gave rise to significant modifications in the instructions, text of the scenarios and response categories. CONCLUSION: IMPLICA is the first questionnaire to evaluate treatment preferences of Crohn´s disease patients receiving biological therapies. This questionnaire facilitates patient´s selection of the most appropriate real world treatment option and, therefore, it can be considered a useful tool when deciding the most appropriate and feasible treatment in normal clinical practice.

Vaccination of patients with inflammatory bowel disease. Practical recommendations.

Patients with inflammatory bowel disease (IBD) have a greater risk of infection associated with the endogenous immunosuppression brought about by their underlying disease as well as the exogenous immunosuppression resulting from their therapies. In the last few years guidelines and consensus papers have been issued on the indication of vaccines for these patients as primary prevention of infection. However, vaccine coverage is low, likely because the risk for infection and both safety and efficacy concerns regarding vaccines are scarcely perceived in such cases. The available scientific evidence shows that immunization is safe for most preparations, and bears no association with an increased risk for disease activity. This paper reviews the available scientific literature, and provides recommendations on the vaccination of adults with IBD.

Questionnaries for measuring fatigue and its impact on health perception in inflammatory bowel disease.

INTRODUCTION: fatigue impacts perceived health, but its importance in inflammatory bowel disease is not known. OBJECTIVES: to define the applicability of the fatigue measurement questionnaires and analyze it in patients with Crohn´s disease and ulcerative colitis. MATERIAL AND METHODS: in a first phase, the psychometric properties of 3 fatigue measurement questionnaires were determined in 99 patients: Daily Fatigue Impact Scale, Fatigue Severity Scale, and Modified Fatigue Impact Scale. In a second phase, fatigue status and its relationship to disease and quality of life was determined in 127 patients and 69 healthy controls. RESULTS: the first part of the study showed the applicability of the questionnaires listed in inflammatory bowel disease, the Daily Fatigue Impact Scale (DFIS) having the best correlation with the quality of life and clinical activity. In the second phase, significantly higher levels of fatigue were observed in active disease than in disease in remission and healthy controls (p < 0,05). The severity of fatigue was significantly correlated with quality of life (r = -0.66 and -0.72 between IBDQ-9 and DFIS and in Crohn´s disease and ulcerative colitis, respectively) and with disease activity (r = 0.25 and Crohn´s disease and ulcerative colitis, respectively, p < 0.05). CONCLUSIONS: in inflammatory bowel disease, fatigue measurement questionnaires have good properties and show that fatigue is an important manifestation of the disease, which has a significant impact on quality of life of patients.

JAK inhibitors: A new dawn for oral therapies in inflammatory bowel diseases.

Inflammatory bowel disease (IBD) is a chronic immune-mediated condition of the gastrointestinal tract that requires chronic treatment and strict surveillance. Development of new monoclonal antibodies targeting one or a few single cytokines, including anti-tumor necrosis factor agents, anti-IL 12/23 inhibitors, and anti-α4ß7 integrin inhibitors, have dominated the pharmacological armamentarium in IBD in the last 20 years. Still, many patients experience incomplete or loss of response or develop serious adverse events and drug discontinuation. Janus kinase (JAK) is key to modulating the signal transduction pathway of several proinflammatory cytokines directly involved in gastrointestinal inflammation and, thus, probably IBD pathogenesis. Targeting the JAK-STAT pathway offers excellent potential for the treatment of IBD. The European Medical Agency has approved three JAK inhibitors for treating adults with moderate to severe Ulcerative Colitis when other treatments, including biological agents, have failed or no longer work or if the patient cannot take them. Although there are currently no approved JAK inhibitors for Crohn's disease, upadacitinib and filgotinib have shown increased remission rates in these patients. Other JAK inhibitors, including gut-selective molecules, are currently being studied IBD. This review will discuss the JAK-STAT pathway, its implication in the pathogenesis of IBD, and the most recent evidence from clinical trials regarding the use of JAK inhibitors and their safety in IBD patients.

Implementation of the recommendations for the psychological management of patients with spondyloarthritis and inflammatory bowel disease.

OBJECTIVE: To assess and improve the level of implementation of the recommendations for the psychological management of patients with spondyloarthritis (SpA) and associated inflammatory bowel disease (IBD). METHODS: Qualitative study. We performed a narrative literature review to identify the recommendations for the psychological management of SpA and associated IBD and to explore their level of implementation. Based on the findings, we developed a national survey to assess: (1) current level of knowledge and implementation of the recommendations; (2) attitudes towards the recommendations; and (3) barriers and facilitators to their implementation. The results of the review and survey were discussed by a multidisciplinary group of 9 expert rheumatologists and gastroenterologists, who defined implementation strategies to increase the uptake of the recommendations. RESULTS: The review included 4 articles, 2 of them included direct recommendations on the identification and management of psychological problems in patients with SpA and IBD. None assessed the level of implementation of the recommendations in routine clinical practice. Our survey showed a great lack of awareness and implementation of the recommendations, even though psychological issues are very relevant for health professionals. Lack of time, resources, and knowledge are considered the main barriers to adherence to the recommendations. We propose several implementation strategies related to educational activities, clinical practice, and others to increase the uptake of reported recommendations. CONCLUSIONS: Further research and efforts are required to achieve behaviour changes in clinical practice to improve the identification and management of psychological problems and needs in patients with SpA and IBD.

A Core Outcome Set for inflammatory bowel diseases: development and recommendations for implementation in clinical practice through an international multi-stakeholder consensus process.

BACKGROUND AND AIMS: Standardising health outcome measurements supports delivery of care, enables data-driven learning systems, and secondary data use for research. As part of the Health Outcomes Observatory initiative and building on existing knowledge, a core outcome set (COS) for inflammatory bowel diseases (IBD) was defined through an international modified Delphi method. METHODS: Stakeholders rated 90 variables on a 9-point importance scale twice, allowing score modification based on feedback displayed per stakeholder group. Two consecutive consensus meetings were held to discuss results and formulate recommendations for measurement in clinical practice. Variables scoring 7 or higher by ≥80% of the participants, or based on consensus meeting agreement, were included in the final set. RESULTS: In total, 136 stakeholders (45 IBD patients (advocates), 74 healthcare professionals/researchers, 13 industry representatives and 4 regulators), from 20 different countries participated. The final set includes 18 case-mix variables, 3 biomarkers (haemoglobin to detect anaemia, C-reactive protein and faecal calprotectin to detect inflammation) for completeness and 28 outcomes (including 16 patient-reported outcomes (PROs) and 1 patient-reported experience). The PRO-2 and IBD-Control questionnaires were recommended to collect disease-specific PROs at every contact with an IBD practitioner, and the Subjective Health Experience model questionnaire, PROMIS Global Health and Self-Efficacy short form to collect generic PROs annually. CONCLUSIONS: A COS for IBD, including a recommendation for use in clinical practice, was defined. Implementation of this set will start in Vienna, Berlin, Barcelona, Leuven and Rotterdam, empowering patients to better manage their care. Additional centres will follow worldwide.

Co Treatment With Biologic Agents and Immunotherapy in the Setting of irAEs of Difficult Management.

In recent years, immunotherapy has become an important pillar of cancer treatment, with high response rates regardless of tumor histology or baseline mutations, sometime in patients without any alternative of treatment. Moreover, these treatments are moving from later line therapies to front-line therapies in the metastasic setting. However, immune activation associated with immune check-point inhibitors (ICI) is not selective and a large variety of immune-related adverse events, with an increasing frequency, have been associated with anti-PD1, anti-PD-1/L-1 and anti-CTLA-4 agents. In clinical trials, and sometimes also in real life practice, patients who develop severe toxicities on ICI-based therapies are usually not allowed to resume ICI once their disease progresses, because of the chance of developing severe irAEs on rechallenge with immunotherapies. Moreover, patients with irAEs suffer important side effects due to the high dose corticosteroids that are used to treat them. Therapy with ICI is sometimes the only alternative for certain patients, and for this reason co treatment with classic (DMARDS) or biologic immunosuppression therapy and ICI must be considered. Co-treatment with this type of immunosuppressant drugs, apart from allowing the maintenance of ICI therapy, drive to a lesser use of corticosteroids, with an improvement of the safety and quality of life of the patients. Such a tailored scheme of treatment is mostly an expert opinion based on recommendation and currently there is scarce evidence supporting it. Herein we present comprehensive, current recommendations and real-world data on the use of co-treatment with ICI and DMARDS and biologic immunosuppression.

Dysbiosis and relapse-related microbiome in inflammatory bowel disease: A shotgun metagenomic approach.

Crohn's disease (CD) and ulcerative colitis (UC), the two main forms of inflammatory bowel disease (IBD), affect several million people worldwide. CD and UC are characterized by periods of clinical remission and relapse. Although IBD patients present chronic alterations of the gut microbiome, called dysbiosis, little attention has been devoted to the relapse-related microbiome. To address this gap, we generated shotgun metagenomic data from the stools of two European cohorts-134 Spanish (followed up for one year) and 49 Belgian (followed up for 6 months) subjects-to characterize the microbial taxonomic and metabolic profiles present. To assess the predictive value of microbiome data, we added the taxonomic profiles generated from a previous study of 130 Americans. Our results revealed that CD was more dysbiotic than UC compared to healthy controls (HC) and that strategies for energy extraction and propionate production were different in CD compared to UC and HC. Remarkably, CD and UC relapses were not associated with alpha- or beta-diversity, or with a dysbiotic score. However, CD relapse was linked to alterations at the species and metabolic pathway levels, including those involved in propionate production. The random forest method using taxonomic profiles allowed the prediction of CD vs. non-CD with an AUC = 0.938, UC vs. HC with an AUC = 0.646, and CD relapse vs. remission with an AUC = 0.769. Our study validates previous taxonomic findings, points to different relapse-related growth and defence mechanisms in CD compared to UC and HC and provides biomarkers to discriminate IBD subtypes and predict disease activity.

Leishmania infantum asymptomatic infection in inflammatory bowel disease patients under anti-TNF therapy.

BACKGROUND: In recent years anti-TNF therapy has been associated with leishmaniasis in immunocompromised patients from endemic areas. Nevertheless, data on asymptomatic Leishmania infection in such patients is scarce. The aim of this study was to determine the prevalence of asymptomatic infection in inflammatory bowel disease (IBD) patients treated with TNF inhibitors living in an endemic area (Catalonia) and to follow up them to study how the infection evolved. METHODS: 192 IBD patients (143 Crohn's disease; 49 ulcerative colitis) from Catalonia (Spain), an area endemic for L. infantum, were recruited. Peripheral blood samples were collected and tested for anti-Leishmania antibodies by Western blotting (WB). Leishmania kinetoplast DNA was detected in peripheral blood mononuclear cells (PBMC) by a quantitative PCR. RESULTS: Serology was positive in 3.1% and Leishmania DNA was found in 8.8%, with a low parasitic load and humoral response. The prevalence was 10.9%, patients being considered infected if they tested positive by at least one of the techniques. Eight out of the 21 patients with asymptomatic leishmaniasis were monitored for 3-8 months after the first test. None of them showed an increased parasitemia or humoral response, or developed leishmaniasis during the follow-up period. CONCLUSION: The prevalence of Leishmania asymptomatic infection detected in our IBD cohort is similar to that found in healthy population in close endemic areas. Due to the short monitoring period, it is not possible to reach a conclusion about the risk of Leishmania reactivation from this study.

Critical role of interleukin (IL)-17 in inflammatory and immune disorders: An updated review of the evidence focusing in controversies.

Interleukin 17 (IL-17) is a proinflammatory cytokine that has been the focus of intensive research because of its crucial role in the pathogenesis of different diseases across many medical specialties. In this context, the present review in which a panel of 13 experts in immunology, dermatology, rheumatology, neurology, hematology, infectious diseases, hepatology, cardiology, ophthalmology and oncology have been involved, puts in common the mechanisms through which IL-17 is considered a molecular target for the development of novel biological therapies in these different fields. A comprehensive review of the literature and analysis of the most outstanding evidence have provided the basis for discussing the most relevant data related to IL-17A blocking agents for the treatment of different disorders, such as psoriasis, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, cardiovascular disorders, non alcoholic fatty liver disease, multiple sclerosis, inflammatory bowel disease, uveitis, hematological and solid cancer. Current controversies are presented giving an opening line for future research.

Fecal excretion of deoxyribonucleic acid in long-term follow-up of patients with inactive ulcerative colitis.

BACKGROUND: We have developed a technique for measuring fecal excretion of human DNA by assuming that luminal desquamation of epithelial and inflammatory cells increases in damaged colonic mucosa. However, the clinical usefulness of this technique in the follow-up of patients with ulcerative colitis has not been established. The aim of this study was to determine the stability of fecal DNA in inactive ulcerative colitis and its potential value as an indicator of relapse. METHODS: The 54 patients with clinically quiescent ulcerative colitis in this prospective study were followed for 12 months or until clinical relapse (clinical activity index > 7). Fecal calprotectin concentration was determined by ELISA, and fecal DNA concentration was determined by quantitative PCR. RESULTS: During the year of follow-up, 23 of the 54 patients relapsed, with a median increase in the colitis activity index from 1.0 to 8.0 (P < 0.01). Median fecal DNA remained unchanged in patients with stable, inactive colitis, ranging from 6.8 copies/microg at inclusion to 1.7 copies/microg at the end of follow-up. Fecal calprotectin level also was unchanged, ranging from 414.0 microg/g at inclusion to 128.9 microg/g at the end of follow-up. In contrast, fecal DNA concentration increased significantly in patients who relapsed (259.0 versus 3.9 copies/microg at entry; P < 0.01). Similar increases in relapsing patients were also observed with fecal calprotectin. ROC curve analysis to assess the accuracy of fecal DNA and calprotectin in detecting relapses during follow-up yielded similar results. CONCLUSIONS: Fecal DNA concentration remained stable in patients with inactive ulcerative colitis but increased significantly with relapses. Determining fecal DNA concentration may be a new objective instrument to use in the follow-up of patients.