Factors related to limitation of life support within 48h of intensive care unit admission: A multicenter study.

OBJECTIVE: To determine factors related to limitations on life support within 48h of intensive care unit (ICU) admission. STUDY DESIGN: Prospective multicenter study. SETTING: Eleven ICUs. PATIENTS: All patients who died and/or had limitations on life support after ICU admission during a four-month period. VARIABLES: Patient characteristics, hospital characteristics, characteristics of limitations on life support. Time-to-first-limitation was classified as early (<48h of admission) or late (≥48h). We performed univariate, multivariate analyses and CHAID (chi-square automatic interaction detection) analysis of variables associated with limitation of life support within 48h of ICU admission. RESULTS: 3335 patients were admitted; 326 (9.8%) had limitations on life support. A total of 344 patients died; 247 (71.8%) had limitations on life support (range among centers, 58.6%-84.2%). The median (p25-p75) time from admission to initial limitation was 2 (0-7) days. CHAID analysis found that the modified Rankin score was the variable most closely related with early limitations. Among patients with Rankin >2, early limitations were implemented in 71.7% (OR=2.5; 95% CI: 1.5-4.4) and lung disease was the variable most strongly associated with early limitations (OR=12.29; 95% CI: 1.63-255.91). Among patients with Rankin ≤2, 48.8% had early limitations; patients admitted after emergency surgery had the highest rate of early limitations (66.7%; OR=2.4; 95% CI: 1.1-5.5). CONCLUSION: Limitations on life support are common, but the practice varies. Quality of life has the greatest impact on decisions to limit life support within 48h of admission.

Potencialidad de donación de órganos en muerte encefálica y limitación del tratamiento de soporte vital en los pacientes neurocríticos / Potential of organ donation in brain death and limitation of life support treatment in neurocritical patients

Objetivo. Analizar el perfil, la incidencia de limitaciónde tratamiento de soporte vital (LTSV) y la potencialidad de donación de órganos enpacientes neurocríticos. Diseño Multicéntrico prospectivo. Ámbito Nueve centros autorizados para extracción de órganos para trasplante...

ETV5 cooperates with LPP as a sensor of extracellular signals and promotes EMT in endometrial carcinomas.

Endometrial carcinoma (EC) is the most frequent among infiltrating tumors of the female genital tract, with myometrial invasion representing an increase in the rate of recurrences and a decrease in survival. We have previously described ETV5 transcription factor associated with myometrial infiltration in human ECs. In this work, we further investigated ETV5 orchestrating downstream effects to confer the tumor the invasive capabilities needed to disseminate in the early stages of EC dissemination. Molecular profiling evidenced ETV5 having a direct role on epithelial-to-mesenchymal transition (EMT). In particular, ETV5 modulated Zeb1 expression and E-Cadherin repression leading to a complete reorganization of cell-cell and cell-substrate contacts. ETV5-promoted EMT resulted in the acquisition of migratory and invasive capabilities in endometrial cell lines. Furthermore, we identified the lipoma-preferred partner protein as a regulatory partner of ETV5, acting as a sensor for extracellular signals promoting tumor invasion. All together, we propose ETV5-transcriptional regulation of the EMT process through a crosstalk with the tumor surrounding microenvironment, as a principal event initiating EC invasion.

Novel molecular profiles of endometrial cancer-new light through old windows.

Endometrial carcinoma (EC) is the most common gynecological malignancy in the western world. A widely accepted dualistic model, which has been established on a morphological basis, differentiates EC into two broad categories: Type I oestrogen-dependent adenocarcinoma with an endometrioid morphology and Type II non-oestrogen-dependent EC with a serous papillary or clear cell morphology. Molecular genetic evidence indicates that endometrial carcinoma, as described in other malignancies, likely develops as the result of a stepwise accumulation of alterations in cellular regulatory pathways, such as oncogene activation and tumor suppressor gene inactivation, which lead to dysfunctional cell growth. These molecular alterations appear to be specific in Type I and Type II cancers. In type I endometrioid endometrial cancer, PTEN gene silencing in conjunction with defects in DNA mismatch repair genes, as evidenced by the microsatellite instability phenotype, or mutations in the K-ras and/or beta-catenin genes, are recognized major alterations, which define the progression of the normal endometrium to hyperplasia, to endometrial intraepithelial neoplasia, and then on to carcinoma. In contrast, Type II cancers show mutations of TP53 and Her-2/neu and seem to arise from a background of atrophic endometrium. Nevertheless, despite the great effort made to establish a molecularly-based histological classification, the following issues must still be clarified: what triggers the tumor cells to invade the myometrium and what causes vascular or lymphatic dissemination, finally culminating in metastasis? RUNX1, a transcription factor, was recently identified as one of the most highly over-expressed genes in a microarray study of invasive endometrial carcinoma. Another candidate gene, which may be associated with an initial switch to myometrial infiltration, is the transcription factor ETV5/ERM. These studies, as well as those conducted for other genes possibly involved in the mitotic checkpoint as a major mechanism of carcinogenesis in non-endometrioid endometrial cancer, could help in understanding the differences in the biology and the clinical outcome among histological types.

Molecular determinants of invasion in endometrial cancer.

Endometrial carcinoma is the most common gynaecological malignancy in the western world and the most frequent among infiltrating tumours of the female genital tract. Despite the characterisation of molecular events associated with the development of endometrial carcinoma, those associated with the early steps of infiltration and invasion in endometrial cancer are less known. Deep myometrial invasion correlates with more undifferentiated tumours, lymph-vascular invasion, node affectation and decreased global survival. In this review we present an overview of the molecular pathology of myometrial infiltration that defines the initial steps of invasion in endometrial cancer. Down-regulation of E-cadherin as a main player of epithelial to mesenchymal transition, as well as modifications on other molecules involved in cell-cell contacts, render cells with a migratory phenotype. In addition, altered signalling pathways and transcription factors associate with myometrial invasion, histologic grade and metastasis.