The correlation between immune subtypes and consensus molecular subtypes in colorectal cancer identifies novel tumour microenvironment profiles, with prognostic and therapeutic implications

Background Solid tumour growth is the consequence of a complex interplay between cancer cells and their microenvironment. Recently, a new global transcriptomic immune classification of solid tumours has identified six immune subtypes (ISs) (C1–C6). Our aim was to specifically characterise ISs in colorectal cancer (CRC) and assess their interplay with the consensus molecular subtypes (CMSs). Methods Clinical and molecular information, including CMSs and ISs, were obtained from The Cancer Genome Atlas (TCGA) (N = 625). Immune cell populations, differential gene expression and gene set enrichment analysis were performed to characterise ISs in the global CRC population by using CMSs. Results Only 5 ISs were identified in CRC, predominantly C1 wound healing (77%) and C2 IFN-γ dominant (17%). CMS1 showed the highest proportion of C2 (53%), whereas C1 was particularly dominant in CMS2 (91%). CMS3 had the highest representation of C3 inflammatory (7%) and C4 lymphocyte depleted ISs (4%), whereas all C6 TGF-β dominant cases belonged to CMS4 (2.3%). Prognostic relevance of ISs in CRC substantially differed from that reported for the global TCGA, and ISs had a greater ability to stratify the prognosis of CRC patients than CMS classification. C2 had higher densities of CD8, CD4 activated, follicular helper T cells, regulatory T cells and neutrophils and the highest M1/M2 polarisation. C2 had a heightened activation of pathways related to the immune system, apoptosis and DNA repair, mTOR signalling and oxidative phosphorylation, whereas C1 was more dependent of metabolic pathways. Conclusions The correlation of IS and CMS allows a more precise categorisation of patients with relevant clinical and biological implications, which may be valuable tools to improve tailored therapeutic interventions in CRC patients.This work was funded by projects DTS15/00157 , PI16/01827 and CIBER-ONC CB16/12/00442 from the Instituto de Salud Carlos III ( Ministry of Economy, Industry and Competitiveness, Spain ) and cofunded by the European Regional Development Fund (ERDF, European Union), and approved by the Ethics Committee or our Institution. BS is funded by AECC (Spain). MCR is funded by Instituto de Salud Carlos III and SEOM (Spain) CCP and BRC are funded by CAM (Programa de Empleo Juvenil (YEI)

International nosocomial infection control consortium (INICC) report, data summary of 36 countries, for 2004-2009

The results of a surveillance study conducted by the International Nosocomial Infection Control Consortium (INICC) from January 2004 through December 2009 in 422 intensive care units (ICUs) of 36 countries in Latin America, Asia, Africa, and Europe are reported. During the 6-year study period, using Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN; formerly the National Nosocomial Infection Surveillance system [NNIS]) definitions for device-associated health care-associated infections, we gathered prospective data from 313,008 patients hospitalized in the consortium's ICUs for an aggregate of 2,194,897 ICU bed-days. Despite the fact that the use of devices in the developing countries' ICUs was remarkably similar to that reported in US ICUs in the CDC's NHSN, rates of device-associated nosocomial infection were significantly higher in the ICUs of the INICC hospitals; the pooled rate of central line-associated bloodstream infection in the INICC ICUs of 6.8 per 1,000 central line-days was more than 3-fold higher than the 2.0 per 1,000 central line-days reported in comparable US ICUs. The overall rate of ventilator-associated pneumonia also was far higher (15.8 vs 3.3 per 1,000 ventilator-days), as was the rate of catheter-associated urinary tract infection (6.3 vs. 3.3 per 1,000 catheter-days). Notably, the frequencies of resistance of Pseudomonas aeruginosa isolates to imipenem (47.2% vs 23.0%), Klebsiella pneumoniae isolates to ceftazidime (76.3% vs 27.1%), Escherichia coli isolates to ceftazidime (66.7% vs 8.1%), Staphylococcus aureus isolates to methicillin (84.4% vs 56.8%), were also higher in the consortium's ICUs, and the crude unadjusted excess mortalities of device-related infections ranged from 7.3% (for catheter-associated urinary tract infection) to 15.2% (for ventilator-associated pneumonia). Copyright © 2012 by the Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved

Surgical treatment of esophageal leiomyoma: an analysis of our experience Tratamiento quirúrgico de leiomioma esofágico: análisis de nuestra experiencia

Introduction: leiomyoma is the most common benign esophageal neoplasm. Surgical treatment (enucleation) has traditionally been the therapy of choice. The advent of minimally invasive techniques has produced an increase in endoscopic approaches to the detriment of open surgery. Objective: the aim of this study was to compare the results obtained with open surgery and with laparoscopic surgery in this kind of pathology. Material and methods: we performed a retrospective study of all leiomyomas operated for in our center between 1986 and 2004, and obtained 9 cases of esophageal leiomyoma. Four were women and five men, between the ages of 40 and 70, with a mean age of 53.5 years. The most frequent symptoms were heartburn (5 cases), dysphagia (3 cases), and retrosternal pain (3 cases). Surgery was in all the cases an enucleation. An open approach was performed in 5 cases (3 thoracotomies and 2 laparotomies), and an endoscopic approach in 4 (2 thoracoscopies and 2 laparoscopies). Results: the mean postoperative hospital stay was 5.12 days (range 2-8 days). This was shorter for endoscopic approaches versus open surgery (3.25 vs. 7 days). There was no case of esophageal mucosal perforation or reconversion. No death, intraoperative complication, or tumor relapse was described. Only 2 patients had complications: post-surgical thoracic pain, and intestinal obstruction by adhesions 8 years after surgery. Conclusion: enucleation is an easier procedure and constitutes the therapy of choice for esophageal leiomyoma. This approach has to be laparoscopic. We think that muscle borders should be closed after enucleation, and that biopsy is not indicated preoperatively.Introducción: el leiomioma es el tumor benigno más frecuente del esófago. Tradicionalmente el tratamiento quirúrgico de estos pacientes consistía en la enucleación. El avance en las técnicas mínimamente invasivas ha provocado un aumento del abordaje endoscópico en detrimento de la cirugía abierta. Objetivo: el objetivo del trabajo fue comparar los resultados obtenidos por vía abierta y por vía laparoscópica en este tipo de patología. Material y métodos: realizamos un estudio retrospectivo de los leiomiomas intervenidos en nuestro centro entre 1986-2004, obteniéndose 9 leiomiomas esofágicos. Cuatro eran mujeres y cinco varones, con unas edades comprendidas entre los 40-70 años, siendo la edad media de 53,5 años. Los síntomas más frecuentes eran pirosis (5 casos), disfagia (3 casos) y dolor retroesternal (3 casos). El tratamiento quirúrgico fue en todos los casos la enucleación. En cinco pacientes se realizó un abordaje abierto (3 toracotomías y 2 laparotomías) y en 4 casos se realizó una laparoscopia (2 toracoscopias y 2 laparoscopias). Resultados: la estancia hospitalaria postoperatoria oscila entre los 2-8 días, con una media de 5,12 días, siendo esta menor en el grupo en el que se realizó cirugía laparoscópica en comparación con el grupo de cirugía abierta (3,25-7 días). No existe ningún caso de perforación de la mucosa esofágica ni de reconversión. Tampoco se describe ningún caso de mortalidad, complicación intraoperatoria ni de recidiva tumoral. Dos pacientes presentan algún tipo de complicaciones: dolor torácico post cirugía, obstrucción intestinal por bridas 8 años después de la cirugía. Conclusión: la enucleación es un procedimiento fácilmente realizable y constituye el tratamiento de elección del leiomioma esofágico. Actualmente el abordaje debe ser laparoscópico. Somos partidarios del cierre de la muscular y bajo nuestro punto de vista la biopsia preoperatoria no está indicada

Structural improvement of higher education in environmental toxicology in Latin America and Europe

The paper reports the results of an international, EU-supported concerted action between Europe and Latin America involving 13 academic institutions from 10 different countries (5 from Europe and 5 from Latin America) aiming to develop a joint core curriculum for higher education and training in environmental toxicology

Structural improvement of higher education in environmental toxicology in Latin America and Europe

Industrial development has resulted in an increased release of chemicals and other agents into the environment, resulting in damage to the environment as well as increasing the risk of adverse effects on human health. Environmental toxicology (ET) is the discipline responsible for assessing the risks to human health and the environment from the effects of new chemicals and those already present in the environment. The development of human resources in toxicology is therefore a priority in both Latin America (LA) and the European Union (EU), although LA professionals are more involved in risk evaluation than in risk assessment compared to their EU colleagues. A solid background in general toxicology will enable those interested in environmental issues to tackle local problems. Moreover, the increasing globalization of markets and, therefore, of the necessary regulations, requires harmonisation of postgraduate programmes to ensure that risk assessment and management related to the environment are dealt with uniformly and by highly qualified scientists. The Inaugural Meeting of the ALFA-OMET project ‘Development, Integration and Harmonisation of Training in Occupational Medicine and Environmental Toxicology’, a 2-year programme supported by the European Commission, offered the opportunity to discuss a number of these issues. The present status of existing ET courses in the EU and LA and the corresponding professional profiles in the two regions were examined, and a harmonized academic curriculum for a postgraduate course in environmental toxicology was developed. Finally, a course programme for toxicology and a specialization in environmental toxicology designed by a panel of experts was discussed, and its relevance as a model for other specialisation programmes was analysed. Exercises such as those performed by ALFA-OMET may be useful not only in promoting discussion for the implementation of national and international professional registers in LA, but also in encouraging the same, ongoing process in the EU