No abstract

No abstract

It has been postulated that brain tumor stem cells (TSCs) may be the population of cells responsible for the maintenance and recurrence of glioblastoma multiforme (GBM). The purpose of this study was to optimize a reproducible protocol for generating TSCs for their subsequent transfection or transduction. Patient GBMs were enzymatically and mechanically dissociated and tumor spheres were resuspended in appropriate media and analyzed to ensure they met stem cell criteria. These cells were then transfected with a plasmid or transduced with a viral vector to introduce a previously absent gene and then allowed to form tumor spheres. Tumor spheres were generated from patient GBMs without contamination. These cells met stringent criteria as stem cells, including multipotentiality and self-renewal. High efficiency transfection and transduction of tumor spheres was possible, even at the core of the sphere. This allowed for the introduction of new genes to the TSCs, as evidenced by fluorescent microscopy and Western blot analysis. This study is a guide to optimize the generation of patient derived GBM tumor spheres without RBC and dead cell contamination. GBM TSCs within tumor spheres can easily be transfected with plasmids or transduced with a virus. This is important from a therapeutic perspective if gene replacement is to be successful in replacing genes lost in GBM progression or to knock down or silence genes that are over-expressed in malignant brain tumors.

It has been hypothesized that cancer stem cells (CSC) may account for the pathogenesis underlying various tumors, including GBM. Markers of these CSCs can be potentially used as therapeutic targets. In this review, we discuss the most recent information regarding CSCs, their molecular biology and their potential role in GBM.

No abstract

IntroductionTraumatic rib fractures result in significant patient morbidity and mortality, which increases with patient age and number of rib fractures. A dedicated acute pain service (APS) providing expertize in multimodal pain management may reduce these risks and improve outcomes. We aimed to test the hypothesis that protocolized APS consultation decreases mortality and morbidity in traumatic rib fracture patients.MethodsThis is a retrospective observational, propensity-matched cohort study of adult patients with trauma with rib fractures from 2012 to 2015, at a single, large level 1 trauma center corresponding to introduction and incorporation of APS consultation into the institutional rib fracture pathway. Using electronic medical records and trauma registry data, we identified adult patients presenting with traumatic rib fractures. Patients with hospital length of stay (LOS) ≥2 days were split into two cohorts based on presence of APS consult using 1:1 propensity matching of age, gender, comorbidities and injury severity. The primary outcome was difference in hospital mortality. Secondary outcomes included LOS and pulmonary morbidity.Results2486 patients were identified, with a final matched cohort of 621 patients receiving APS consult and 621 control patients. The mortality rate was 1.8% among consult patients and 6.6% among control patients (adjusted OR 0.25, 95% CI 0.13 to 0.50; p=0.001). The average treatment effect of consult on mortality was 4.8% (95% CI 1.2% to 8.5%;. p<0.001). APS consultation was associated with increased intensive care unit (ICU) LOS (1.19 day; 95% CI 0.48 to 1.90; p=0.001) and hospital LOS (1.61 days; 95% CI 0.81 to 2.41 days; p<0.001). No difference in pulmonary complications was observed.DiscussionAn APS consult in rib fracture patients is associated with decreased mortality and no difference in pulmonary complications yet increased ICU and hospital LOS.

No abstract

No abstract