Anti‑TNF agents and new biological agents (Vedolizumab and Ustekinumab) in the prevention and treatment of postoperative recurrence after surgery in crohn’s disease

Surgery for Crohn’s disease (CD) is not curative, as postoperative recurrence (POR) after ileocolonic resection is the rule in the absence of prophylactic treatment. In the present article, we critically review available data on the role of anti-tumour necrosis factor (TNF) agents and new biologics (including vedolizumab and ustekinumab) in the prevention and treatment of POR after surgery in CD. Several studies (summarised in various meta-analyses) have confrmed the efcacy of anti-TNFs in the prevention of POR. We identifed 37 studies, including 1863 CD patients, with mean endoscopic POR at 6–12 months of 29%. Only few randomised controlled trials (RCTs) have directly compared thiopurines and anti-TNFs, with controversial results, although the superiority of the latter is supported by several meta-analyses. Infiximab and adalimumab seem equally efective. The combination of anti-TNFs and immunosuppressives should be considered in patients previously exposed to anti-TNFs. Several studies have shown that anti-TNFs remain an efective option to prevent POR also in patients with anti-TNF failure before surgery. In fact, the use of the same anti-TNF before and after surgery might be efective for the prevention of POR. Prophylactic anti-TNF treatment, once started, should be continued long term. Anti-TNFs are also efective for the treatment of established POR. Retreatment with anti-TNFs for POR is a valid strategy even after their preoperative failure. In six studies (including 156 patients) evaluating vedolizumab, mean endoscopic POR at 6–12 months was 41%. The non-randomised comparison of anti-TNFs and vedolizumab has provided controversial results. One placebo-controlled RCT confrmed that vedolizumab is quite efective in preventing POR in CD patients with increased risk of recurrence. Seven studies (including 162 patients) evaluated ustekinumab, with a mean endoscopic POR at 6–12 months of 41%. The comparative efcacy of ustekinumab and anti-TNFs is still unclear. Ustekinumab and vedolizumab seem to be equally efective, although the experience is very limited. In conclusion, to date, anti-TNFs are the most efective agents in preventing and treating POR in CD. Anti-TNFs remain an efective option to prevent POR also in patients with anti-TNF failure before surgery. Vedolizumab seems to be quite efective in the prevention of POR in patients with increased risk of recurrence. Ustekinumab is probably also efective in the postoperative setting, although the comparative efcacy with anti-TNFs or vedolizumab is still unclea

Frequency and effectiveness of empirical anti-tnf dose intensification in inflammatory bowel disease: Systematic review with meta-analysis

Loss of response to antitumor necrosis factor (anti-TNF) therapies in inflammatory bowel disease occurs in a high proportion of patients. Our aim was to evaluate the loss of response to anti-TNF therapy, considered as the need for dose intensification (DI), DI effectiveness and the possible variables influencing its requirements. Bibliographical searches were performed. Selection: prospective and retrospective studies assessing DI in Crohn’s disease and ulcerative colitis patients treated for at least 12 weeks with an anti-TNF drug. Exclusion criteria: studies using anti-TNF as a prophylaxis for the postoperative recurrence in Crohn’s disease or those where DI was based on therapeutic drug monitoring. Data synthesis: effectiveness by intention-to-treat (random effects model). Data were stratified by medical condition (ulcerative colitis vs. Crohn’s disease), anti-TNF drug and follow-up. Results: One hundred and seventy-three studies (33,241 patients) were included. Overall rate of the DI requirement after 12 months was 28% (95% CI 24–32, I2 = 96%, 41 studies) in naïve patients and 39% (95% CI 31–47, I2 = 86%, 18 studies) in non-naïve patients. The DI requirement rate was higher both in those with prior anti-TNF exposure (p = 0.01) and with ulcerative colitis (p = 0.02). The DI requirement rate in naïve patients after 36 months was 35% (95% CI 28–43%; I2 = 98%; 18 studies). The overall short-term response and remission rates of empirical DI in naïve patients were 63% (95% CI 48–78%; I2 = 99%; 32 studies) and 48% (95% CI: 39–58%; I2 = 92%; 25 studies), respectively. The loss of response to anti-TNF agents—and, consequently, DI—occurred frequently in inflammatory bowel disease (approximately in one-fourth at one year and in one-third at 3 years). Empirical DI was a relatively effective therapeutic option

Systematic review: The gut microbiome and its potential clinical application in inflammatory bowel disease

Inflammatory bowel disease (IBD) is a chronic relapsing-remitting systemic disease of the gastrointestinal tract. It is well established that the gut microbiome has a profound impact on IBD pathogenesis. Our aim was to systematically review the literature on the IBD gut microbiome and its usefulness to provide microbiome-based biomarkers. A systematic search of the online bibliographic database PubMed from inception to August 2020 with screening in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted. One-hundred and forty-four papers were eligible for inclusion. There was a wide heterogeneity in microbiome analysis methods or experimental design. The IBD intestinal microbiome was generally characterized by reduced species richness and diversity, and lower temporal stability, while changes in the gut microbiome seemed to play a pivotal role in determining the onset of IBD. Multiple studies have identified certain microbial taxa that are enriched or depleted in IBD, including bacteria, fungi, viruses, and archaea. The two main features in this sense are the decrease in beneficial bacteria and the increase in pathogenic bacteria. Significant differences were also present between remission and relapse IBD status. Shifts in gut microbial community composition and abundance have proven to be valuable as diagnostic biomarkers. The gut microbiome plays a major role in IBD, yet studies need to go from casualty to causality. Longitudinal designs including newly diagnosed treatment-naïve patients are needed to provide insights into the role of microbes in the onset of intestinal inflammation. A better understanding of the human gut microbiome could provide innovative targets for diagnosis, prognosis, treatment and even cure of this relevant disease.This work is supported by Sara Borrell contract CD19/00247 from the Instituto de Salud Carlos III (ISCIII) to L.A.-G

¿Es rentable para el sector público invertir en educación?

The present paper analyzes one of the advantages that a country can derive from people with higher educational levels, i.e. higher tax revenues resulting from the higher earnings from higher school attainment.More specifically, we test whether the marginal revenue obtained by the public sector from taxpayers holding an additional educational level is higher than the marginal public expenditure on them. To accomplish this aim, we extend Psacharopoulos (1981) analysis and calculate internal rates of return for public expenditure in schooling. Our results suggest that taxpayers with an additional educational level, including those attaining post-compulsory educational levels, are profitable for the public sector.Education expenditure, tax burden, internal rate of return.

The Receptor-Like Kinase SERK3/BAK1 Is Required for Basal Resistance against the Late Blight Pathogen Phytophthora infestans in Nicotiana benthamiana

BACKGROUND The filamentous oomycete plant pathogen Phytophthora infestans causes late blight, an economically important disease, on members of the nightshade family (Solanaceae), such as the crop plants potato and tomato. The related plant Nicotiana benthamiana is a model system to study plant-pathogen interactions, and the susceptibility of N. benthamiana to Phytophthora species varies from susceptible to resistant. Little is known about the extent to which plant basal immunity, mediated by membrane receptors that recognise conserved pathogen-associated molecular patterns (PAMPs), contributes to P. infestans resistance. PRINCIPAL FINDINGS We found that different species of Phytophthora have varying degrees of virulence on N. benthamiana ranging from avirulence (incompatible interaction) to moderate virulence through to full aggressiveness. The leucine-rich repeat receptor-like kinase (LRR-RLK) BAK1/SERK3 is a major modulator of PAMP-triggered immunity (PTI) in Arabidopsis thaliana and N. benthamiana. We cloned two NbSerk3 homologs, NbSerk3A and NbSerk3B, from N. benthamiana based on sequence similarity to the A. thaliana gene. N. benthamiana plants silenced for NbSerk3 showed markedly enhanced susceptibility to P. infestans infection but were not altered in resistance to Phytophthora mirabilis, a sister species of P. infestans that specializes on a different host plant. Furthermore, silencing of NbSerk3 reduced the cell death response triggered by the INF1, a secreted P. infestans protein with features of PAMPs. CONCLUSIONS/SIGNIFICANCE We demonstrated that N. benthamiana NbSERK3 significantly contributes to resistance to P. infestans and regulates the immune responses triggered by the P. infestans PAMP protein INF1. In the future, the identification of novel surface receptors that associate with NbSERK3A and/or NbSERK3B should lead to the identification of new receptors that mediate recognition of oomycete PAMPs, such as INF1.This work was supported by the Gatsby Charitable Foundation, BBSRC, Nuffield Foundation and the German Research Foundation (DFG). SS was supported by a personal research fellowship (SCHO1347/1-1). JPR is an Australian Research Council Future Fellow (FT0992129). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Editorial: Teaching history in the era of globalization: epistemological and methodological challenges

The COVID-19 pandemic has highlighted the need of several changes within the field of History Education. Firstly, the need of a methodological change that integrates active learning methods, digital resources, and emerging technologies in order to attend the non-presential lessons for the students. Secondly, the need of a multicultural approach on teaching history, social, and gender equality moving away from supremacists' dogma. It is necessary for teachers to change their conception of why and for what reasons they teach history. This need has become more acute with the COVID-19 pandemic: fighting vs. hate speeches through argumentation and critical analysis of sources to avoid fake news and to develop a learning perception evidences. This Research Topic is focused both on Primary and Secondary Education, but also on Higher Education, considering History teachers training courses. Particularly, this book focuses to know the development of the skills of active and future History teachers who are trained at programs at universities to bring a profound methodological and content change in the way History is taught..

The interplay between immune system and microbiota in inflammatory bowel disease: A narrative review

The importance of the gut microbiota in human health is currently well established. It contributes to many vital functions such as development of the host immune system, digestion and metabolism, barrier against pathogens or brain–gut communication. Microbial colonization occurs during infancy in parallel with maturation of the host immune system; therefore, an adequate cross‐talk between these processes is essential to generating tolerance to gut microbiota early in life, which is crucial to prevent allergic and immune‐mediated diseases. Inflammatory bowel disease (IBD) is characterized by an exacerbated immune reaction against intestinal microbiota. Changes in abundance in the gut of certain microorganisms such as bacteria, fungi, viruses, and archaea have been associated with IBD. Microbes that are commonly found in high abundance in healthy gut microbiomes, such as F. prausnitzii or R. hominis, are reduced in IBD patients. E. coli, which is usually present in a healthy gut in very low concentrations, is increased in the gut of IBD patients. Microbial taxa influence the immune system, hence affecting the inflammatory status of the host. This review examines the IBD microbiome profile and presents IBD as a model of dysbiosis.This study was supported by Instituto de Salud Carlos III (ISCIII), Spain (grant numbers PI16/01296 and PI19/01034), by Sara Borrell contract CD19/00247 to L.A.-G. and by CIBEReh

La problemática del aprendiz en la etapa productiva

El documento presenta los resultados de encuestas aplicadas a aprendices de diferentes especialidades en los tres periodos productivos asociadas a determinar los diferentes problemas y dificultades que el aprendiz de industria en etapa productiva puede encontrar en las empresa, describe la percepción del aprendiz con la empresa y viceversa, se analizan las condiciones laborales, grado de satisfacción, aplicación de conocimientos obtenidos en el SENA entre otros aspectosThe document presents the results of surveys applied to apprentices of different specialties in the three productive periods associated with determining the different problems and difficulties that the productive sector apprentice can find in the company, describes the apprentice's perception with the company and vice versa , the working conditions, degree of satisfaction, application of knowledge obtained in the SENA among other aspects are analyze