SUMMARY Glial progenitor cells (GPCs) are a potential source of malignant gliomas. We used A2B5-based sorting to extract tumorigenic GPCs from human gliomas spanning WHO grades II-IV. mRNA profiling identified a cohort of genes that distinguished tumor-initiating progenitor cells (TPCs) from A2B5+ GPCs isolated from normal white matter. A core set of genes and pathways was substantially dysregulated in A2B5+ TPCs, that included the transcription factor SIX1, and its principal co-factors, EYA1 and DACH2. shRNAi silencing of SIX1 inhibited the expansion of glioma TPCs in vitro and in vivo, suggesting a critical and unrecognized role of the SIX1-EYA1-DACH2 system in glioma genesis or progression. By comparing the expression patterns of glioma TPCs to normal GPCs, we have identified a discrete set of pathways by which glial tumorigenesis may be better understood, and more specifically targeted.

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Background Stroke mechanisms and the risk of recurrent thromboembolism are incompletely understood in patients with primary brain tumors. We sought to better delineate these important clinical features. Methods We performed a retrospective cohort study of adults with primary brain tumors diagnosed with MRI-confirmed acute ischemic stroke at Memorial Sloan Kettering Cancer Center from 2005 to 2015. Study neurologists collected data on patients’ cancer history, stroke risk factors, treatments, and outcomes. Stroke mechanisms were adjudicated by consensus. The primary outcome was recurrent thromboembolism (arterial or venous) and the secondary outcome was recurrent ischemic stroke. Kaplan-Meier statistics were used to calculate cumulative outcome rates, and Cox hazards analysis was used to evaluate the association between potential risk factors and outcomes. Results We identified 83 patients with primary brain tumors and symptomatic acute ischemic stroke. Median survival after index stroke was 2.2 years (interquartile range, 0.5–7.0). Tumors were mostly gliomas (72%) and meningiomas (13%). Most strokes were from unconventional mechanisms, particularly radiation vasculopathy (36%) and surgical manipulation (18%). Small-or large-vessel disease or cardioembolism caused 13% of strokes, while 29% were cryptogenic. Cumulative recurrent thromboembolism rates were 11% at 30 days, 17% at 180 days, and 27% at 365 days; while cumulative recurrent stroke rates were 5% at 30 days, 11% at 180 days, and 13% at 365 days. We found no significant predictors of outcomes. Conclusions Patients with primary brain tumors generally develop strokes from rare mechanisms and their risk of recurrent thromboembolism, including stroke, is high.

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Introduction: Narrative approaches to assessment provide meaningful and valid representations of trainee performance. Yet, narratives are frequently perceived as vague, nonspecific and low quality. To date, there is little research examining factors associated with narrative evaluation quality, particularly in undergraduate medical education. The purpose of this study was to examine associations of faculty-and student-level characteristics with the quality of faculty member's narrative evaluations of clerkship students. Methods:The authors reviewed faculty narrative evaluations of 50 students' clinical performance in their inpatient medicine and neurology clerkships, resulting in 165 and 87 unique evaluations in the respective clerkships. The authors evaluated narrative quality using the Narrative Evaluation Quality Instrument (NEQI). The authors used linear mixed effects modelling to predict total NEQI score. Explanatory covariates included the following: time to evaluation completion, number of weeks spent with student, faculty total weeks on service per year, total faculty years in clinical education, student gender, faculty gender, and an interaction term between student and faculty gender.Results: Significantly higher narrative evaluation quality was associated with a shorter time to evaluation completion, with NEQI scores decreasing by approximately 0.3 points every 10 days following students' rotations (p = .004).Additionally, women faculty had statistically higher quality narrative evaluations with NEQI scores 1.92 points greater than men faculty (p = .012). All other covariates were not significant. Conclusions:The quality of faculty members' narrative evaluations of medical students was associated with time to evaluation completion and faculty gender but not faculty experience in clinical education, faculty weeks on service, or the amount of time spent with students. Findings advance understanding on ways to improve the quality of narrative evaluations which are imperative given assessment models that will increase the volume and reliance on narratives.

Introduction: Patients with systemic cancer often develop acute ischemic stroke from unique mechanisms, including cancer-mediated hypercoagulability, and their risk of recurrence is high. Conversely, stroke mechanisms in patients with primary brain tumors are incompletely understood, and the risk of recurrent thromboembolism in these patients is uncertain. Methods: We performed a retrospective cohort study of adult patients treated for a primary brain tumor at Memorial Sloan Kettering Cancer Center who were diagnosed with MRI-confirmed acute ischemic stroke from 2005 to 2015. Study neurologists used all available electronic records to collect data on patients’ cancer history, stroke risk factors, treatments, and outcomes. Stroke mechanisms, including the TOAST stroke subtype classification, were adjudicated by consensus. The primary outcome was recurrent thromboembolism (arterial or venous) and the secondary outcome was recurrent ischemic stroke. Kaplan-Meier survival statistics were used to calculate cumulative outcome rates, and multivariate Cox proportional hazards analysis was used to evaluate the association between several prespecified potential risk factors and outcomes. Results: We identified 83 patients with primary brain tumors and acute ischemic stroke. Median age was 60 years (IQR 51-67) and 53% were women. Tumors were mostly gliomas (72%) and meningiomas (13%). Prior head and neck radiotherapy was common (71%). Most strokes were from unconventional mechanisms, particularly radiation vasculopathy (36%) and surgical manipulation (19%). Small- or large-vessel disease or cardioembolism caused 13% of strokes, while 28% were cryptogenic. Median survival from index stroke was 2.2 years. Cumulative rates of recurrent thromboembolism were 11% at 30 days, 17% at 180 days, and 27% at 360 days; while cumulative rates of recurrent stroke were 5% at 30 days, 8% at 180 days, and 13% at 360 days. We found no significant predictors of outcomes, although radiation vasculopathy was nonsignificantly associated with recurrent stroke (HR 2.4, 95% CI 0.7-7.8). Conclusions: Patients with primary brain tumors generally develop strokes from unique mechanisms and their risk of recurrence is high.

Background: About 5% of acute ischemic stroke (AIS) patients have active cancer. Previous work has shown that cancer patients are more likely to die after AIS than non-cancer patients. However, few data exist on how these disparities are changing over time. Methods: We identified all patients hospitalized with AIS in the National Inpatient Sample from 1996-2013 using validated ICD-9 diagnosis codes. Our primary predictor was systemic cancer, which was a composite of solid and hematologic tumors with or without metastases. Primary brain tumors were excluded. Our primary outcome was in-hospital death. Survey weights were used to estimate nationally-representative annual rates of in-hospital death among AIS patients with and without cancer. Multivariable logistic regression models adjusting for age, gender, and race were constructed to evaluate the relationship between time, cancer history, and mortality. Results: We identified 9.6 million patients with AIS, of whom 491,704 (5.1%) had cancer. The in-hospital death rate among stroke patients with cancer decreased from 21.7% (95% confidence interval [CI], 20.6-22.9%) in 1996 to 13.9% (95% CI, 13.0-14.7%) in 2013, while the death rate among stroke patients without cancer decreased from 9.9% (95% CI, 9.6-10.1%) in 1996 to 6.4% (95% CI, 6.2-6.6%) in 2013 (Figure). After adjustment for demographics, a cancer diagnosis was associated with more than a doubling in odds of death after AIS (odds ratio [OR] 2.34; 95% CI, 2.29-2.38). However, during the 18-year study period, the demographic-adjusted odds of in-hospital death after AIS decreased similarly over time in patients with cancer (OR per year 0.97; 95% CI, 0.96-0.97) as compared to those without (OR per year 0.97; 95% CI, 0.97-0.98). Conclusions: Despite improved mortality rates over time, cancer patients with AIS continue to face more than a two-fold increased risk of in-hospital death as compared to non-cancer AIS patients.