Modelo para la mejora del acceso y permanencia de grupos vulnerables en educación secundaria postobligatoria (APESE)

El presente documento es resultado del Proyecto 'Acceso y permanencia de grupos vulnerables en la educación secundaria no obligatoria. Creación y validación de un modelo de intervención' financiado por la convocatoria de I+D RETOS (EDU2013-47452-R). Presenta el Modelo de Acceso y Permanencia en la Educación Secundaria Postobligatoria [APESE] desarrollado para el contexto de la educación secundaria postobligatoria, con el objetivo de asegurar una transición más pertinente desde la enseñanza secundaria obligatoria y mayores tasas de éxito en esta etapa para los colectivos identificados como vulnerables (prioritariamente, estudiantes con un nivel socioeconómico bajo, inmigrantes, gitanos, personas con discapacidad y género

IL-6 serum levels predict severity and response to tocilizumab in COVID-19: An observational study

Background: Patients with coronavirus disaese 2019 (COVID-19) can develop a cytokine release syndrome that eventually leads to acute respiratory distress syndrome requiring invasive mechanical ventilation (IMV). Because IL-6 is a relevant cytokine in acute respiratory distress syndrome, the blockade of its receptor with tocilizumab (TCZ) could reduce mortality and/or morbidity in severe COVID-19. Objective: We sought to determine whether baseline IL-6 serum levels can predict the need for IMV and the response to TCZ. Methods: A retrospective observational study was performed in hospitalized patients diagnosed with COVID-19. Clinical information and laboratory findings, including IL-6 levels, were collected approximately 3 and 9 days after admission to be matched with preadministration and postadministration of TCZ. Multivariable logistic and linear regressions and survival analysis were performed depending on outcomes: need for IMV, evolution of arterial oxygen tension/fraction of inspired oxygen ratio, or mortality. Results: One hundred forty-six patients were studied, predominantly males (66%); median age was 63 years. Forty-four patients (30%) required IMV, and 58 patients (40%) received treatment with TCZ. IL-6 levels greater than 30 pg/mL was the best predictor for IMV (odds ratio, 7.1; P < .001). Early administration of TCZ was associated with improvement in oxygenation (arterial oxygen tension/fraction of inspired oxygen ratio) in patients with high IL-6 (P = .048). Patients with high IL-6 not treated with TCZ showed high mortality (hazard ratio, 4.6; P = .003), as well as those with low IL-6 treated with TCZ (hazard ratio, 3.6; P = .016). No relevant serious adverse events were observed in TCZ-treated patients. Conclusions: Baseline IL-6 greater than 30 pg/mL predicts IMV requirement in patients with COVID-19 and contributes to establish an adequate indication for TCZ administrationThis study was funded by Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and Instituto de Salud Carlos III (grant nos. RD16/0011/0012 and PI18/ 0371 to I.G.A., grant no. PI19/00549 to A.A., and grant no. SAF2017-82886-R to F.S.-M.) and co-funded by the European Regional Development Fund. The study was also funded by ‘‘La Caixa Banking Foundation’’ (grant no. HR17-00016 to F.S.-M.) and ‘‘Fondos Supera COVID19’’ by Banco de Santander and CRUE. None of these sponsors have had any role in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publicatio

Spatiotemporal Characteristics of the Largest HIV-1 CRF02_AG Outbreak in Spain: Evidence for Onward Transmissions

Background and Aim: The circulating recombinant form 02_AG (CRF02_AG) is the predominant clade among the human immunodeficiency virus type-1 (HIV-1) non-Bs with a prevalence of 5.97% (95% Confidence Interval-CI: 5.41–6.57%) across Spain. Our aim was to estimate the levels of regional clustering for CRF02_AG and the spatiotemporal characteristics of the largest CRF02_AG subepidemic in Spain.Methods: We studied 396 CRF02_AG sequences obtained from HIV-1 diagnosed patients during 2000–2014 from 10 autonomous communities of Spain. Phylogenetic analysis was performed on the 391 CRF02_AG sequences along with all globally sampled CRF02_AG sequences (N = 3,302) as references. Phylodynamic and phylogeographic analysis was performed to the largest CRF02_AG monophyletic cluster by a Bayesian method in BEAST v1.8.0 and by reconstructing ancestral states using the criterion of parsimony in Mesquite v3.4, respectively.Results: The HIV-1 CRF02_AG prevalence differed across Spanish autonomous communities we sampled from (p &lt; 0.001). Phylogenetic analysis revealed that 52.7% of the CRF02_AG sequences formed 56 monophyletic clusters, with a range of 2–79 sequences. The CRF02_AG regional dispersal differed across Spain (p = 0.003), as suggested by monophyletic clustering. For the largest monophyletic cluster (subepidemic) (N = 79), 49.4% of the clustered sequences originated from Madrid, while most sequences (51.9%) had been obtained from men having sex with men (MSM). Molecular clock analysis suggested that the origin (tMRCA) of the CRF02_AG subepidemic was in 2002 (median estimate; 95% Highest Posterior Density-HPD interval: 1999–2004). Additionally, we found significant clustering within the CRF02_AG subepidemic according to the ethnic origin.Conclusion: CRF02_AG has been introduced as a result of multiple introductions in Spain, following regional dispersal in several cases. We showed that CRF02_AG transmissions were mostly due to regional dispersal in Spain. The hot-spot for the largest CRF02_AG regional subepidemic in Spain was in Madrid associated with MSM transmission risk group. The existence of subepidemics suggest that several spillovers occurred from Madrid to other areas. CRF02_AG sequences from Hispanics were clustered in a separate subclade suggesting no linkage between the local and Hispanic subepidemics

Valor pronóstico de los factores clinicopatológicos y marcadores inmunohistoquímicos en pacientes con cáncer gástrico operado : modelos predictivos, afectación ganglionar y clasificación molecular

Tesis inédita de la Universidad Complutense de Madrid, Facultad de Medicina, leída el 17-05-2023. Tesis formato europeo (compendio de artículos)El cáncer gástrico (CG) es una enfermedad agresiva que suele diagnosticarse en estadios avanzados, con una tasa de supervivencia a 5 años inferior al 30%. Presenta variabilidad geográfica, con diferencias importantes entre pacientes asiáticos y occidentales. La única clasificación que determina el manejo del CG en la práctica clínica es el sistema anatómico TNM. Sin embargo, el CG es una entidad heterogénea que incluso ha mostrado variabilidad en el pronóstico de pacientes en el mismo estadio TNM y recidivas precoces en estadios tempranos. Puede clasificarse de acuerdo a diversos factores, como la localización de las lesiones o sus características macroscópicas, histológicas o moleculares. En cuanto a su morfología endoscópica o macroscópica, se utiliza el sistema de París en el CG temprano y la clasificación de Borrmann en el CG avanzado. Las clasificaciones histológicas más utilizadas son la de Laurén y la de la Organización Mundial de la Salud. El sistema de Laurén se desarrolló como una clasificación “histoclínica” y recientemente se ha correlacionado con las características moleculares del CG. Además, se han publicado diversas clasificaciones moleculares, siendo las más importantes las del Atlas del Genoma del Cáncer (TCGA) y el Grupo Asiático de Investigación en Cáncer (ACRG). A pesar de los avances que se han producido en la patología molecular del cáncer en los últimos años, el pronóstico de los pacientes con CG continúa siendo malo y los tratamientos disponibles han mostrado un beneficio limitado. Múltiples investigadores han destacado la necesidad de estratificar a los pacientes en base a otros factores tanto en ensayos clínicos como para la selección del tratamiento, porque la mala categorización de los casos podría ser una causa importante de la eficacia limitada del tratamiento actual del CG. Asimismo, la identificación de nuevos marcadores pronósticos y terapéuticos sería de gran utilidad para mejorar el pronóstico de los pacientes con CG...Gastric cancer (GC) is an aggressive disease with an estimated 5-year survival rate of less than 30%. It shows significant geographic variation, and important differences have been reported between patients from Western and Asian countries. The main prognostic tool for patient stratification is the TNM system. However, GC is a heterogeneous disease. Prognostic outcomes of patients at the same stage are variable, and some authors have reported early recurrences in cases of initial GC. GC can be classified according to several features, including tumor location, gross morphology, histology or molecular alterations. Macroscopically, the Paris system and the Borrmann classification are applicable in cases of early and advanced GC, respectively. The main histological classifications are the Laurén and the World Health Organization systems. Laurén classification was developed as a “histo-clinical” system, and it has been recently correlated to the molecular features of GC. In addition, several molecular classifications have been published, the most important being The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG) classifications. Despite recent advances in the molecular pathology of cancer, patient prognosis in GC is still poor, with limited treatment effectiveness. Several investigators have highlighted the need to refine the stratification of GC cases for clinical trials and patient management, because the deficiencies in the classification of GC may explain the limited value of the current therapeutic options. Moreover, the identification of new prognostic and therapeutic markers may be useful for improving patient prognosis...Fac. de MedicinaTRUEunpu

Hereditary Gastrointestinal Tumor Syndromes: When Risk Comes with Your Genes

Despite recent campaigns for screening and the latest advances in cancer therapy and molecular biology, gastrointestinal (GI) neoplasms remain among the most frequent and lethal human tumors. Most GI neoplasms are sporadic, but there are some well-known familial syndromes associated with a significant risk of developing both benign and malignant GI tumors. Although some of these entities were described more than a century ago based on clinical grounds, the increasing molecular information obtained with high-throughput techniques has shed light on the pathogenesis of several of them. The vast amount of information gained from next-generation sequencing has led to the identification of some high-risk genetic variants, although others remain to be discovered. The opportunity for genetic assessment and counseling in these families has dramatically changed the management of these syndromes, though it has also resulted in significant psychological distress for the affected patients, especially those with indeterminate variants. Herein, we aim to summarize the most relevant hereditary cancer syndromes involving the stomach and colon, with an emphasis on new molecular findings, novel entities, and recent changes in the management of these patients

Molecular Classifications in Gastric Cancer: A Call for Interdisciplinary Collaboration

Gastric cancer (GC) is a heterogeneous disease, often diagnosed at advanced stages, with a 5-year survival rate of approximately 20%. Despite notable technological advancements in cancer research over the past decades, their impact on GC management and outcomes has been limited. Numerous molecular alterations have been identified in GC, leading to various molecular classifications, such as those developed by The Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG). Other authors have proposed alternative perspectives, including immune, proteomic, or epigenetic-based classifications. However, molecular stratification has not yet transitioned into clinical practice for GC, and little attention has been paid to alternative molecular classifications. In this review, we explore diverse molecular classifications in GC from a practical point of view, emphasizing their relationships with clinicopathological factors, prognosis, and therapeutic approaches. We have focused on classifications beyond those of TCGA and the ACRG, which have been less extensively reviewed previously. Additionally, we discuss the challenges that must be overcome to ensure their impact on patient treatment and prognosis. This review aims to serve as a practical framework to understand the molecular landscape of GC, facilitate the development of consensus molecular categories, and guide the design of innovative molecular studies in the field

Neuroendocrine neoplasms in rare locations: Clinicopathological features and review of the literature

Introduction: Neuroendocrine tumors (NETs) occur more often in lungs, gastrointestinal tract, or pancreas. Data about terminology and grading of NETs in rare locations are scarce and variable, and they have been reported mainly as case reports. Materials and Methods: We here describe our experience with NETs in unusual locations. We have reviewed all NETs diagnosed in our institution and summarized their clinicopathological features. We have also reviewed the literature and discussed the main characteristics of NETs in each site. Results: Two hundred and forty-three primary NETs were diagnosed. About 55.2% of patients were men and the mean age was 62 years. About 90.7% of NETs were located in lungs, gastrointestinal tract, or pancreas, and 50.8% of them were low-grade tumors. We identified 13 NETs in rare locations: breast, ovary, endometrium, vulva, uterine cervix, extrahepatic biliary tract, kidney, sinonasal tract, and thymus. Three additional tumors were diagnosed by the senior author in other institution. Patients were asymptomatic or presented with nonspecific symptoms. All NETs were treated with surgery and 31% of patients received adjuvant therapy. There were 10 Grade 3 (62.5%), 2 Grade 2 (12.5%), and 4 Grade 1 (25%) tumors. Mean follow-up was 72 months. About 60% of G3 tumors recurred or progressed. G2 tumors were located in breast, and both patients are stable. About 50% of G1 tumors recurred or progressed (both renal NETs). Conclusions: NETs in rare locations are heterogeneous, and their behavior does not seem to correlate absolutely with tumor grade. More studies are needed to clarify the role of proliferation rate in these tumors

Prognostic role of tissue transglutaminase 2 in colon carcinoma

24 p.-4 fig.Tissue transglutaminase 2 (TG2) is involved in many biological processes, from wound healing to neurodegeneration. Recently, there has been an increasing interest in this enzyme as a potential prognostic marker or therapy target in human neoplasms. The aim of this study was to analyze expression of TG2 messenger RNA (mRNA) and protein in colon cancer samples and to evaluate the potential value of TG2 as prognostic marker. We investigated not only expression level but also location of the protein in a series of human tumors. In silico analysis using the GSE39582 dataset showed that TG2 mRNA expression is associated with earlier relapse. The results of qPCR in our cohort showed TG2 mRNA to be up-regulated in 25 out of 70 samples (34 %). Kaplan-Meier plots and log-rank test showed that patients with high TG2 mRNA expression have significantly worse prognosis in terms of overall survival (OS) and a trend to earlier recurrence. Immunohistochemical staining of tumor sections for TG2 revealed stromal staining in 152 cases (88 %) and epithelial cell staining in 105 cases (62 %). In stage II patients, stromal expression showed a significant association with disease-free survival (DFS). In patients with metastatic disease, TG2 expression was also associated with poor prognosis. Cox multivariate analysis showed that TG2 expression in epithelial cells is significantly and independently associated with OS, together with node involvement and presence of metastasis. Stromal TG2 expression was associated with DFS. In summary, in non-metastatic colorectal cancer patients, stromal TG2 expression is significantly associated with DFS and epithelial TG2 expression with OS, independently of node involvement and metastasis.This research was supported by grants BIO2012–31,023 and BIO2015–66,489-R from the MINECO and PRB2 (IPT13/0001-ISCIII-SGEFI/FEDER) from the Instituto de Salud Carlos III-FEDER.Peer reviewe