Quantification of ICG-based fluorescence angiography appears to be useful for intraoperative monitoring of arterial patency and regional cerebral blood flow.

Cancer cells upregulate anabolic processes to maintain high rates of cellular turnover. Limiting the supply of macromolecular precursors by targeting enzymes involved in biosynthesis is a promising strategy in cancer therapy. Several tumors excessively metabolize glutamine to generate precursors for nonessential amino acids, nucleotides, and lipids, in a process called glutaminolysis. Here we show that pharmacological inhibition of glutaminase (GLS) eradicates glioblastoma stem-like cells (GSCs), a small cell subpopulation in glioblastoma (GBM) responsible for therapy resistance and tumor recurrence. Treatment with small molecule inhibitors compound 968 and CB839 effectively diminished cell growth and in vitro clonogenicity of GSC neurosphere cultures. However, our pharmaco-metabolic studies revealed that only CB839 inhibited GLS enzymatic activity thereby limiting the influx of glutamine derivates into the TCA cycle. Nevertheless, the effects of both inhibitors were highly GLS specific, since treatment sensitivity markedly correlated with GLS protein expression. Strikingly, we found GLS overexpressed in in vitro GSC models as compared with neural stem cells (NSC). Moreover, our study demonstrates the usefulness of in vitro pharmacometabolomics to score target specificity of compounds thereby refining drug development and risk assessment.

BACKGROUND AND PURPOSE: Impairment of tissue oxygenation caused by inhomogeneous microscopic blood flow distribution, the so-called capillary transit time heterogeneity, is thought to contribute to delayed cerebral ischemia after aneurysmal SAH but has so far not been systematically evaluated in patients. We hypothesized that heterogeneity of the MTT, derived from CTP parameters, would give insight into the clinical course of patients with aneurysmal SAH and may identify patients at risk of poor outcome. MATERIALS AND METHODS:We retrospectively analyzed the heterogeneity of the MTT using the coefficient of variation in CTP scans from 132 patients. A multivariable logistic regression model was used to model the dichotomized mRS outcome. Linear regression was used to eliminate variables with high linear dependence. T tests were used to compare the means of 2 groups. Furthermore, the time of the maximum coefficient of variation for MTT after bleeding was evaluated for correlation with the mRS after 6 months. RESULTS:On average, each patient underwent 5.3 CTP scans during his or her stay. Patients with high coefficient of variation for MTT presented more often with higher modified Fisher (P ¼ .011) and World Federation of Neurosurgical Societies grades (P ¼ .014). A high coefficient of variation for MTT at days 3-21 after aneurysmal SAH correlated significantly with a worse mRS score after 6 months (P ¼ .016). We found no correlation between the time of the maximum coefficient of variation for MTT after bleeding and the patients' outcomes after 6 months (P ¼ .203).CONCLUSIONS: Heterogeneity of MTT in CTP after aneurysmal SAH correlates with the patients' outcomes. Because the findings are in line with the pathophysiologic concept of the capillary transit time heterogeneity, future studies should seek to verify the coefficient of variation for MTT as a potential imaging biomarker for outcome. ABBREVIATIONS: aSAH ¼ aneurysmal SAH; CTH ¼ capillary transit time heterogeneity; cvMTT ¼ coefficient of variation for MTT; cvMTT-peak ¼ maximum cvMTT after bleeding; DCI ¼ delayed cerebral ischemia; EVD ¼ external ventricular drainage; ICP ¼ intracranial pressure; RTH ¼ relative transit time heterogeneity; Tmax ¼ time-to-maximum; WFNS ¼ World Federation of Neurosurgical Societies

Objectives Lennox‐Gastaut syndrome (LGS) is among the most severe epileptic and developmental encephalopathies. A meta‐analysis was performed to evaluate the effectiveness of adjunctive vagus nerve stimulation (VNS Therapy) in patients with LGS. Materials & Methods PubMed database was queried (January 1997 to September 2018) to identify publications reporting on the efficacy of VNS Therapy in patients with LGS, with or without safety findings. Primary endpoint of the meta‐analysis was the proportion of responders (≥50% reduction in seizure frequency). Random‐effects analysis was used to calculate weighted mean estimates and confidence intervals. Heterogeneity was evaluated by statistical tests including I2. Results Of 2752 citations reviewed, 17 articles (480 patients) were eligible including 10 retrospective studies and seven prospective studies. A random‐effects model produced a pooled proportion of 54% (95% confidence intervals [CI]: 45%, 64%) of patients with LGS who responded to adjunctive VNS Therapy (p for heterogeneity <0.001, I2=72.9%). Per an exploratory analysis, the calculated incidence of serious adverse events associated with VNS Therapy was 9% (95% CI: 5%, 14%); the rate was higher than in long‐term efficacy studies of heterogeneous cohorts with drug‐resistant epilepsy and likely attributed to variable definitions of serious adverse events across studies. Conclusions The meta‐analysis of 480 patients with LGS suggests that 54% of patients responded to adjunctive VNS Therapy and that the treatment option was safe and well‐tolerated. The response in patients with LGS was comparable to heterogeneous drug‐resistant epilepsy populations. A clinical and surgical overview has been included to facilitate the use of VNS in LGS.