Summary Background Patients with gastrointestinal bleeding during anticoagulant and/or antiplatelet therapy represent a clinical challenge. Aim To determine the risk/rates of rebleeding, vascular events and death in patients treated with antiplatelet or anticoagulant agents who developed major gastrointestinal bleeding Methods This was an observational cohort study of patients who developed gastrointestinal bleeding while on antiplatelet and/or anticoagulant therapy. Drug use information was collected prospectively during bleeding events. Cox proportional hazards models were used to evaluate rebleeding, vascular events and death. Results Among 871 patients (mean age 78.9 ± 8.6 years), 38.9% used an anticoagulant, 52.5% used an antiplatelet and 8.6% used both; 93.1% interrupted treatment after gastrointestinal bleeding and 80.5% restarted therapy within 7.6 ± 36.4 days; 38.7% had upper gastrointestinal bleeds, 46.7% lower gastrointestinal bleeds and 14.6% gastrointestinal bleeds of unknown origin. Median follow‐up was 24.9 months (IQR: 7.0‐38.0). Resumption of both therapies was associated with a higher risk of rebleeding, lower risk of ischaemic events or death and a similar risk for upper and lower gastrointestinal events. Resumption of therapy ≤ 7 days after bleeding showed a similar pattern with no differences in death. Rebleeding rates were higher in anticoagulant vs antiplatelet patients (138.0 vs 99.0 events per 1000 patient‐years), and the bleeding location was identical in 61.8% of cases. Conclusions Resumption of anticoagulant or antiplatelet therapy after a gastrointestinal bleeding event was associated with a lower risk of vascular events and death and a higher rebleeding risk. The benefits of early reinstitution of anticoagulant/antiplatelet therapy outweigh the gastrointestinal‐related risks.

Background Management of Helicobacter pylori infection has been expanded from the gastroenterology specialist (GS) to primary care physicians (PCPs), with a large increase in requests for urea breath tests (UBT). Due to the lack of evidence at this level, we evaluated the appropriateness of UBT indications and treatment for H pylori infections between PCPs and GSs and the effect of introducing specific counseling to PCPs. Materials and Methods This was a quasi‐experimental study. Phase I included 650 consecutive UBT requested by PCPs (400) and GSs (250). Indications and treatments were classified as appropriate or inappropriate based on national guidelines. Data on eradication rates were also collected. In phase II, 240 UBT and patients' treatment outcomes were analyzed after individually counseling PCPs on both aspects. Results Of 1049 UBT, inappropriate indications in phase I were significantly higher in tests requested by PCP compared with GS (35.9% vs 7.2%; P < 0.001). Inappropriate treatment regimens were significantly higher for PCPs in phase I (65.8% vs 26.4%; P < 0.001). Consequently, eradication rates were significantly lower in patients treated by PCPs compared with those treated by GS (63.7% vs 81.4%; P = 0.004). A significant increase in adherence to appropriate treatment regimens (75.8% vs 34.2%; P < 0.001) and eradication rates (79.2% vs 63.7%; P = 0.002) were observed in the PCP group after counseling; however, the appropriateness of indications did not improve. Conclusions Patients infected with H pylori managed at the primary care level had poorer outcomes. The introduction of specific counseling for PCPs significantly improved treatment management, but not indications.

Background and Aims Clinical trials and real-life studies with ustekinumab in Crohn's disease (CD) have shown a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. Methods Elderly patients (&gt;60 years old) from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-TNF use and smoking habit. Values for the Harvey-Bradshaw Index (HBI), endoscopic activity, C-reactive protein (CRP), and faecal calprotectin (FC) were recorded at baseline and at weeks 16, 32 and 54. Results 648 patients were included, 212 elderlies. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remision was similar at week 16 (54.6 vs 51.4%, p=0.20), 32 (53.0% vs 54.5%, p=0.26) and 54 (57.8% vs 51.1%, p=0.21). Persistence of ustekinumab as maintenance therapy was similar in both age groups (log-rank test; p=0.91). There was no difference in the rate of adverse effects (14.2% vs 11.2%, p=0.350), including severe infections (7.1% vs 7.3%, p=1.00), except for the occurrence of de novo neoplasms, which was higher in older patients (0.7% vs 4.3%, p= 0.003). Conclusions Ustekinumab is as effective in elderly patients with CD, as it is in non-elderly. Safety profile seems to be also similar but for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.

Thiopurines have been a cornerstone in the treatment of inflammatory bowel disease (IBD). Although they have been used for more than 50 years, there are still some unsolved issues about their efficacy and, also, some safety concerns, mainly the risk of myelosuppression and life-threatening lymphoproliferative disorders. Furthermore, the development of biological therapy raises the question whether there is still a role for thiopurines in the IBD treatment algorithm. On the other hand, limited cost and wide availability make thiopurines a reasonable option in settings of limited resources and increasing prevalence of IBD. In fact, there is a growing interest in optimizing thiopurine therapy, since pharmacogenomic findings suggest that a personalized approach based on the genotyping of some molecules involved in its metabolism could be useful to prevent side effects. Polymorphisms of thiopurine methyltransferase enzyme (TPMT) that result in low enzymatic activity have been associated with an increased risk of myelotoxicity, especially in Caucasians; however, in Asians it is assumed that the variants of nudix hydrolase 15 (NUDT15) are more relevant in the development of toxicity. Age is also important, since in elderly patients the risk of complications seems to be increased. Moreover, the primo-infection of Epstein Barr virus and cytomegalovirus under thiopurine treatment has been associated with severe lymphoproliferative disorders. In addition to assessing individual characteristics that may influence thiopurines treatment outcomes, this review also discusses other strategies to optimize the therapy. Low-dose thiopurines combined with allopurinol can be used in hypermethylators and in thiopurine-related hepatotoxicity. The measurement of metabolites could be useful to assess compliance, identify patients at risk of adverse events and also facilitating the management of refractory patients. Thioguanine is also a rescue therapy in patients with toxicity related to conventional thiopurine therapy. Finally, the current indications for thiopurines in monotherapy or in combination with biologics, as well as the optimal duration of treatment, are also reviewed.

Background. Calcineurin inhibitor-induced neurotoxicity (CIIN) is a common and debilitating side effect after liver transplantation (LT). Risk factors and impact on patient outcomes are not well defined. Our aim was to assess the incidence, risk factors, and clinical outcomes of CIIN. Methods. We retrospectively analyzed 175 LTs performed at our center between January 2010 and September 2016. Donor and recipient demographics as well as clinical variables pre-LT, intra-LT, and post-LT were assessed. All patients were on once-daily prolonged-release tacrolimus. Results. CIIN was described in 37 (21.4%) recipients. In univariate analysis, history of hepatic encephalopathy (P = 0.033), immunosuppressant treatment protocol (P = 0.041), donor age (P = 0.002), and pre-LT sodium serum levels (P = 0.004) were associated with CIIN. Patients undergoing LT for hepatocellular carcinoma had lower rates of CIIN (P = 0.040). In multivariate analysis, hepatic encephalopathy (odds ratio [OR], 2.728; 95% confidence interval [CI], 1.098-6.779; P = 0.031), pre-LT serum sodium levels (OR, 1.118 per mEq/L increase, 95% CI, 1.021-1.224; P = 0.016), and donor age (OR, 1.032 per y increase; 95% CI, 1.004-1.062; P = 0.027) were independent risk factors for developing CIIN. In the CIIN group, patients had longer intensive care unit (P = 0.024) and hospital (P = 0.008) stays and more changes in immunosuppressive treatment (54.1% vs 20.4%; P < 0.001). Conclusions. Neurotoxicity remains frequent in patients on once-daily prolonged-release tacrolimus. Antecedents of hepatic encephalopathy, pre-LT sodium serum levels, and donor age are independent risk factors for developing CIIN after LT. CIIN is associated with longer hospital stays and changes in immunosuppressive treatment.

Chronic inflammation in patients with Inflammatory Bowel Disease (IBD) leads to an increased risk of colorectal cancer, small bowel cancer, intestinal lymphoma and cholangiocarcinoma. However, treatments for IBD have also been associated with an increased risk of neoplasms. Patients receiving Thiopurines (TPs) have an increased risk of hematologic malignancies, non-melanoma skin cancer, urinary tract neoplasms and cervical cancer. Anti-TNFs have been associated with a higher risk of neoplasms, mainly lymphomas and melanomas; however, the data are controversial, and some recent studies do not confirm the association. Nevertheless, other biologic agents, such as ustekinumab and vedolizumab, have not shown an increased risk of any neoplasm to date. The risk of malignancies with tofacitinib exists, but its magnitude and relationship with previous treatment with TPs is not defined, so more studies from daily clinical practice are needed. Although biologic therapy seems to be safe for patients with current cancer or a prior history of cancer, as has been demonstrated in other chronic inflammatory conditions, prospective studies in this specific population are needed. Until that time, it is crucial to manage such conditions via the combined clinical expertise of the gastroenterologist and oncologist.

The availability of biologic therapies in inflammatory bowel disease (IBD) is increasing significantly. This represents more options to treat patients, but also more difficulties in choosing the therapies, especially in the context of bio-naïve patients. Most evidence of safety and efficacy came from clinical trials comparing biologics with placebo, with a lack of head-to-head studies. Network meta-analysis of biologics and real-world studies have been developed to solve this problem. Despite the results of these studies, there are also other important factors to consider before choosing the biologic, such as patient preferences, comorbidities, genetics, and inflammatory markers. Given that resources are limited, another important aspect is the cost of biologic therapy, since biosimilars are widely available and have been demonstrated to be effective with a significant decrease in costs. In this review, we summarize the evidence comparing biologic therapy in both Crohn´s disease (CD) and ulcerative colitis (UC) in different clinical situations. We also briefly synthesize the evidence related to predictors of biologic response, as well as the biologic use in extraintestinal manifestations and the importance of the drug-related costs.

BackgroundPrevious studies comparing immigrant ethnic groups and native patients with IBD have yielded clinical and phenotypic differences. To date, no study has focused on the immigrant IBD population in Spain.MethodsProspective, observational, multicenter study comparing cohorts of IBD patients from ENEIDA-registry who were born outside Spain with a cohort of native patients.ResultsWe included 13,524 patients (1,864 immigrant and 11,660 native). The immigrants were younger (45 ± 12 vs. 54 ± 16 years, p &lt; 0.001), had been diagnosed younger (31 ± 12 vs. 36 ± 15 years, p &lt; 0.001), and had a shorter disease duration (14 ± 7 vs. 18 ± 8 years, p &lt; 0.001) than native patients. Family history of IBD (9 vs. 14%, p &lt; 0.001) and smoking (30 vs. 40%, p &lt; 0.001) were more frequent among native patients. The most prevalent ethnic groups among immigrants were Caucasian (41.5%), followed by Latin American (30.8%), Arab (18.3%), and Asian (6.7%). Extraintestinal manifestations, mainly musculoskeletal affections, were more frequent in immigrants (19 vs. 11%, p &lt; 0.001). Use of biologics, mainly anti-TNF, was greater in immigrants (36 vs. 29%, p &lt; 0.001). The risk of having extraintestinal manifestations [OR: 2.23 (1.92–2.58, p &lt; 0.001)] and using biologics [OR: 1.13 (1.0–1.26, p = 0.042)] was independently associated with immigrant status in the multivariate analyses.ConclusionsCompared with native-born patients, first-generation-immigrant IBD patients in Spain were younger at disease onset and showed an increased risk of having extraintestinal manifestations and using biologics. Our study suggests a featured phenotype of immigrant IBD patients in Spain, and constitutes a new landmark in the epidemiological characterization of immigrant IBD populations in Southern Europe.