Neurosurgery
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Differences between centers in patient outcome after subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysms could be of relevance for the design of multicenter studies, particularly randomized clinical trials (RCTs), and standardization of management practices for improved quality of care for all patients. This study was aimed at investigating whether differences in outcome exist between centers enrolling patients into RCTs in SAH, and, if so, quantifying such center effect. ⋯ The outcomes of patients who are enrolled into multicenter clinical trials in SAH differ considerably between centers and regions. The reasons and implications of these findings should be studied, as such might lead to improvement in some aspects of trial design and management practices.
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Glioblastoma is the most common and aggressive primary human brain cancer. Noninvasive characterization of intratumor blood flow parameters may help guide clinical decision making. Beyond risk stratification and prognostication, tumor perfusion may inform treatment selection and serial monitoring of newer antiangiogenic targeted therapies. In this study, intra- and intertumor variations in blood volume were quantified by using a novel 3-D volumetric, dynamic-susceptibility contrast-enhanced (DSCE), T2*-weighted perfusion magnetic resonance (MR) analysis to determine associations with molecular features and clinical outcomes. ⋯ A distinct vasculogenic subtype of glioblastoma identified by quantitative MR perfusion voxel-based analysis was associated with unique molecular features and worse overall survival. Quantitative volumetric MR perfusion holds potential in characterizing intra- and intertumoral heterogeneity, and identifying biologically distinct, clinically relevant subsets of patients for risk stratification and treatment selection.
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Low-grade gliomas (LGGs) comprise a diverse set of intrinsic brain tumors that correlate strongly with survival. Data on the effect of reoperation are sparse. ⋯ This is among the largest studies to assess variables associated with outcome in patients with reoperated LGG. Reresection appears to provide significant benefit, and extent of resection remains the strongest predictor of OS.
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Human ether a go-go-related-1 (hERG) is a voltage-dependent K+ channel overexpressed in GBM cell lines, and linked to aberrant proliferation. The FDA mandates all drugs undergo cardiotoxicity profiling that includes hERG inhibition. We analyzed hERG expression in glioblastoma stemlike cell (GSC)-derived tumor models and a clinically annotated human GBM tissue microarray (TMA) to correlate with patient survival after hERG expression stratification. ⋯ We showed that GBM xenografts with higher hERG expression had higher proliferation rates, and the addition of 2 known hERG inhibitors (phenytoin, E-4031) inhibited sphere formation in high hERG-expressing GSC lines. GBM TMA analyses showed significantly better survival in high hERG-expressing GBM patients treated with hERG inhibitory drugs. These data suggest clinical trials for already FDA-approved drugs that also inhibit hERG in high hERG-expressing GBM patients.
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Our recent study showed that maintaining a higher hemoglobin threshold after severe traumatic brain injury (TBI) offers no clinical benefit. The present study aimed to determine if a higher transfusion threshold was independently associated with an increased risk of progressive hemorrhagic injury (PHI), thereby contributing to higher rates of morbidity and mortality. ⋯ Our analysis shows that a higher transfusion threshold of 10 g/dL after severe TBI increased the risk of severe PHI events. These results indicate the potential adverse effect of using a higher transfusion threshold after severe TBI.