Disease severity in familial cases of IBD

Background: Phenotypic traits of familial IBD relative to sporadic cases are controversial, probably related to limited statistical power of published evidence. Aim: To know if there are phenotype differences between familial and sporadic IBD, evaluating the prospective Spanish registry (ENEIDA) with 11,983 cases. Methods: 5783 patients (48.3%) had ulcerative colitis (UC) and 6200 (51.7%) Crohn's disease (CD). Cases with one or more 1st, 2nd or 3rd degree relatives affected by UC/CD were defined as familial case. Results: In UC and CD, familial cases compared with sporadic cases had an earlier disease onset (UC: 33 years [IQR 25–44] vs 37 years [IQR 27–49]; p b 0.0001); (CD: 27 years [IQR 21–35] vs 29 years [IQR 22–40]; p b 0.0001), higher prevalence of extraintestinal immune-related manifestations (EIMs) (UC: 17.2% vs 14%; p = 0.04); (CD: 30.1% vs 23.6%; p b 0.0001). Familial CD had higher percentage of ileocolic location (42.7% vs 51.8%; p = 0.0001), penetrating behavior (21% vs 17.6%; p = 0.01) and perianal disease (32% vs 27.1%; p = 0.003). Differences are not influenced by degree of consanguinity. Conclusion: When a sufficiently powered cohort is evaluated, familial aggregation in IBD is associated to an earlier disease onset, more EIMs and more severe phenotype in CD. This feature should be taken into account at establishing predictors of disease course

Unraveling the real magnitude of illegal wildlife poisoning to halt cryptic biodiversity loss

Illegal wildlife poisoning is a global threat for biodiversity, yet the magnitude of its impact on ecosystems is largely underestimated as most of poisoning episodes remain undetected. Here, we conducted a large-scale field experiment to better understand the real dimension of the illegal wildlife poisoning in terms of composition and number of species and abundance of impacted individuals, as well as the ecological factors driving it. We used camera traps to monitor simulated poison baits placed in 25 study areas in SW Europe and applied Good–Turing theory to estimate the richness of species of the entire assemblage (observed plus undetected). We recorded 3095 individuals from 39 vertebrate species that consumed 94 % of the baits (N = 590). Yet, using sample completeness to estimate the entire species assemblage yielded a total of 47 species exposed to illegal poisoning. The observed assemblage included different trophic and functional groups (from lizards and snakes to apex species among birds and mammals), as well as a 38 % of threatened and near threatened species (according to Spanish and Portuguese vertebrate red list and UICN list). The size (weight) of the bait outstands as a reliable predictor of the number of species (0–8 species/bait, mean = 2) and individuals (0–99 individuals/bait, mean = 5) susceptible to poisoning. The habitat where the bait was placed modulated the abundance of individuals affected (greater in open than in closed habitats). Type of bait and habitat drove the compositional variation of species. Our approach enables uncover entire species assemblages prone to illegal poisoning and their ecological drivers associated, advancing the understanding of the impact of wildlife poisoning in ecosystemsThis work was supported by the project TOXICO funding by “BBVA FOUNDATION GRANTS TO SCIENTIFIC RESEARCH TEAMS, CALL 2018”. WWF Spain and SEO/BirdLife provided access to the ANTíDOTO database of wildlife poisoning in Spain. The Ohio Wesleyan University supported with logistical material (5 camera-traps). JVLB was supported by the Spanish Ministry of Economy, Industry and Competitiveness (RYC-2015-18932; CGL2017-87528-R AEI/FEDER EU). JVLB and PMT were supported by a GRUPIN research grant from the Regional Government of Asturias (AYUD/2021/51314). In Portugal, this study was financed through the Sentinelas project funded by Fundo Ambiental – Minist´erio do Ambiente e da Aç˜ ao Clim´ atica. We are grateful to Instituto da Conservaçao ˜ da Natureza e das Florestas (ICNF), Principado de Asturias, Junta de Castilla y Leon, ´ Xunta de Galicia, Gobierno de Cantabria, Comunidad de Madrid, Junta de Andalucía, Picos de Europa National Park, Sierra de Guadarrama National Park, Cabaneros ˜ National Park and Monfragüe National Park for granted permission

Effectiveness and Safety of the Sequential Use of a Second and Third Anti-TNF Agent in Patients with Inflammatory Bowel Disease: Results from the Eneida Registry

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

Evolution after Anti-TNF Discontinuation in Patients with Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study

OBJECTIVES:The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed.METHODS:This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included.RESULTS:A total of 1, 055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn''s disease and ulcerative colitis patients, respectively. In both Crohn''s disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn''s disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe.CONCLUSIONS:The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe

Treatment patterns and intensification within 5 year of follow-up of the first-line anti-TNFα used for the treatment of IBD: results from the VERNE study

Background Anti-TNFα represent one of the main treatment approaches for the management of inflammatory bowel diseases (IBD). Therefore,the evaluation of their treatment patterns over time provides valuable insights about the clinical value of therapies and associated costs. Aims To assess the treatment patterns with the first anti-TNFα in IBD. Methods Retrospective, observational study. Results 310 IBD patients were analyzed along a 5-year follow-up period. 56.2% of Crohn's disease (CD) patients started with adalimumab (ADA), while 43.8% started with infliximab (IFX). 12.9% of ulcerative colitis (UC) patients initiated with ADA, while 87.1% initiated with IFX. Treatment intensification was required in 28.9% of CD and 37.1% of UC patients. Median time to treatment intensification was shorter in UC than in CD (5.3 vs. 14.3 months; p = 0.028). Treatment discontinuation due to reasons other than remission were observed in 40.7% of CD and 40.5% of UC patients, although, in UC patients there was a trend to lower discontinuation rates with IFX (36.6%) than with ADA (66.7%). Loss of response accounted for approximately one-third of discontinuations, in both CD and UC. Conclusions Around one-third of IBD biologic-naive patients treated with an anti-TNFα required treatment intensification (earlier in UC) and around 40% discontinued the anti-TNFα due to inappropriate disease control

Identification by Real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues

MicroRNAs (miRNAs) are short non-coding RNA molecules playing regulatory roles by repressing translation or cleaving RNA transcripts. Although the number of verified human miRNA is still expanding, only few have been functionally described. However, emerging evidences suggest the potential involvement of altered regulation of miRNA in pathogenesis of cancers and these genes are thought to function as both tumours suppressor and oncogenes. In our study, we examined by Real-Time PCR the expression of 156 mature miRNA in colorectal cancer. The analysis by several bioinformatics algorithms of colorectal tumours and adjacent non-neoplastic tissues from patients and colorectal cancer cell lines allowed identifying a group of 13 miRNA whose expression is significantly altered in this tumor. The most significantly deregulated miRNA being miR-31, miR-96, miR-133b, miR-135b, miR-145, and miR-183. In addition, the expression level of miR-31 was correlated with the stage of CRC tumor. Our results suggest that miRNA expression profile could have relevance to the biological and clinical behavior of colorectal neoplasia