Glioblastoma multiforme (GBM) is a devastating tumour with abysmal prognoses. We desperately need novel approaches to understand GBM biology and therapeutic vulnerabilities. Extracellular vesicles (EVs) are membrane-enclosed nanospheres released locally and systemically by all cells, including tumours, with tremendous potential for intercellular communication. Tumour EVs manipulate their local environments as well as distal targets; EVs may be a mechanism for tumourigenesis in the recurrent GBM setting. We hypothesized that GBM EVs drive molecular changes in normal human astrocytes (NHAs), yielding phenotypically tumour-promoting, or even tumourigenic, entities. We incubated NHAs with GBM EVs and examined the astrocytes for changes in cell migration, cytokine release and tumour cell growth promotion via the conditioned media. We measured alterations in intracellular signalling and transformation capacity (astrocyte growth in soft agar). GBM EV-treated NHAs displayed increased migratory capacity, along with enhanced cytokine production which promoted tumour cell growth. GBM EV-treated NHAs developed tumour-like signalling patterns and exhibited colony formation in soft agar, reminiscent of tumour cells themselves. GBM EVs modify the local environment to benefit the tumour itself, co-opting neighbouring astrocytes to promote tumour growth, and perhaps even driving astrocytes to a tumourigenic phenotype. Such biological activities could have profound impacts in the recurrent GBM setting.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.

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Background Coagulopathy is associated with massive transfusion (MT) in trauma, yet most clinical scores to predict this outcome do not incorporate coagulation assays. Previous work has identified that shock increases circulating tissue plasminogen activator(tPA). When tPA levels saturate endogenous inhibitors, systemic hyperfibrinolysis can occur. Therefore, the addition of tPA to a patient’s blood sample could stratify a patients underlying degree of shock and early coagulation changes to predict progression to MT. We hypothesize that a modified thrombelastography (TEG) assay with exogenous tPA, will unmask patients impending risk of MT. Study Design Trauma activations were analyzed using rapid TEG(R-TEG) and a modified TEG assay wuth low (Lt-TEG) and high dose of tPA(Ht-TEG). Clinical scores(Shock Index [SI], ABC, and TASH,) were compared to TEG measurements to predict the need for MT, using the areas under the receiver operating characteristic curves. Results 324 patients were analyzed, 17% required MT. MT patients had a median SI=1.2, ABC score=1, and TASH score=12. R-TEG and tPA TEG parameters were different significantly different in all MT patients compared to non-MT patients (all p<0.02). The Lt-LY30 (lysis at 30 minutes) had the largest AUROC (0.86, 95%CI 0.79–0.93) for prediction of MT similar to INR0.86 (95%CI 0.81–0.91) followed by TASH (0.83, (95%CI 0.77–0.89). Combing INR and tPA-TEG variables results in a positive prediction of MT in 49% of patients with a 98% negative predictive value. Conclusion tPA-TEG identifies trauma patients who require MT efficiently, in a single assay that can be completed in a shorter time than other scoring systems, which has improved performance when combined with INR. This new method is consistent with our understanding of the molecular events responsible for trauma-induced coagulopathy.

OBJECTIVE Prophylactic use of antiepileptic drugs (AEDs) in seizure-naïve brain tumor patients remains a topic of debate. This study aimed to characterize a subset of patients at highest risk for new-onset perioperative seizures (i.e., intraoperative and postoperative seizures occurring within 30 days of surgery) who may benefit from prophylactic AEDs. METHODS The authors conducted a retrospective case-control study of all adults who had undergone tumor resection or biopsy at the authors' institution between January 1, 2004, and June 31, 2015. All patients with a history of preoperative seizures, posterior fossa tumors, pituitary tumors, and parasellar tumors were excluded. A control group was matched to the seizure patients according to age (± 0 years). Demographic data, clinical status, operative data, and postoperative course data were collected and analyzed. RESULTS Among 1693 patients who underwent tumor resection or biopsy, 549 (32.4%) had never had a preoperative seizure. Of these 549 patients, 25 (4.6%) suffered a perioperative seizure (Group 1). A total of 524 patients (95.4%) who remained seizure free were matched to Group 1 according to age (± 0 years), resulting in 132 control patients (Group 2), at an approximate ratio of 1:5. There were no differences between the patient groups in terms of age, sex, race, relationship status, and neurological deficits on presentation. Histological subtype (infiltrating glioma vs meningioma vs other, p = 0.041), intradural tumor location (p < 0.001), intraoperative cortical stimulation (p = 0.004), and extent of resection (less than gross total, p = 0.002) were associated with the occurrence of perioperative seizures. CONCLUSIONS While most seizure-naïve brain tumor patients do not benefit from perioperative seizure prophylaxis, such treatment should be considered in high-risk patients with supratentorial intradural tumors, in patients undergoing intraoperative cortical stimulation, and in patients in whom subtotal resection is likely.