Hypoxia-Mediated Mechanisms Associated with Antiangiogenic Treatment Resistance in Glioblastomas.

Glioblastomas (GBMs) are malignant tumors characterized by their vascularity and invasive capabilities. Antiangiogenic therapy (AAT) is a treatment option that targets GBM-associated vasculature to mitigate the growth of GBMs. However, AAT demonstrates transient effects because many patients eventually develop resistance to this treatment. Several recent studies attempt to explain the molecular and biochemical basis of resistance to AAT in GBM patients. Experimental investigations suggest that the induction of extensive intratumoral hypoxia plays a key role in GBM escape from AAT. In this review, we examine AAT resistance in GBMs, with an emphasis on six potential hypoxia-mediated mechanisms: enhanced invasion and migration, including increased expression of matrix metalloproteinases and activation of the c-MET tyrosine kinase pathway; shifts in cellular metabolism, including up-regulation of hypoxia inducible factor-1α's downstream processes and the Warburg effect; induction of autophagy; augmentation of GBM stem cell self-renewal; possible implications of GBM-endothelial cell transdifferentiation; and vasoformative responses, including vasculogenesis, alternative angiogenic pathways, and vascular mimicry. Juxtaposing recent studies on well-established resistance pathways with that of emerging mechanisms highlights the overall complexity of GBM treatment resistance while also providing direction for further investigation.

Intraoperative Spinal Cord and Nerve Root Monitoring: A Hospital Survey and Review.

Intraoperative monitoring (IOM) of spinal cord and nerve root injury through somatosensory evoked potentials (SSEP), transcranial motor evoked potentials (TcMEP), spontaneous electromyography (sEMG), and triggered electromyography (tEMG) modalities is vital during spinal surgery. However, there are currently no practice guidelines or practice patterns for the utilization of unimodal and multimodal IOM for specific surgeries. This study reviews IOM modalities and documents practice patterns of spine surgeons at our single-center tertiary hospital about their use of various IOM modalities on 23 spinal procedures. As different intraoperative monitoring modalities have shown to have different sensitivities and specificities, devising practice guidelines for IOM utilization in specific spinal procedures should be considered.

Efficacy of tranexamic acid on surgical bleeding in spine surgery: a meta-analysis.

BACKGROUND CONTEXT: Spine surgery is usually associated with large amount of blood loss, necessitating blood transfusions. Blood loss-associated morbidity can be because of direct risks, such as hypotension and organ damage, or as a result of blood transfusions. The antifibrinolytic, tranexamic acid (TXA), is a lysine analog that inhibits activation of plasminogen and has shown to be beneficial in reducing surgical blood loss. PURPOSE: To consolidate the findings of randomized controlled trials (RCTs) investigating the use of TXA on surgical bleeding in spine surgery. STUDY DESIGN: A metaanalysis. STUDY SAMPLE: Randomized controlled trials investigating the effectiveness of intravenous TXA in reducing blood loss in spine surgery, compared with a placebo/no treatment group. METHODS: MEDLINE, Embase, Cochrane controlled trials register, and Google Scholar were used to identify RCTs published before January 2014 that examined the effectiveness of intravenous TXA on reduction of blood loss and blood transfusions, compared with a placebo/no treatment group in spine surgery. Metaanalysis was performed using RevMan 5. Weighted mean difference with 95% confidence intervals was used to summarize the findings across the trials for continuous outcomes. Dichotomous data were expressed as risk ratios with 95% confidence intervals. A p<.05 was considered statistically significant. RESULTS: Eleven RCTs were included for TXA (644 total patients). Tranexamic acid reduced intraoperative, postoperative, and total blood loss by an average of 219 mL ([-322, -116], p<.05), 119 mL ([-141, -98], p<.05), and 202 mL ([-299, -105], p<.05), respectively. Tranexamic acid led to a reduction in proportion of patients who received a blood transfusion (risk ratio 0.67 [0.54, 0.83], p<.05) relative to placebo. There was one myocardial infarction (MI) in the TXA group and one deep vein thrombosis (DVT) in placebo. CONCLUSIONS: Tranexamic acid reduces surgical bleeding and transfusion requirements in patients undergoing spine surgery. Tranexamic acid does not appear to be associated with an increased incidence of pulmonary embolism, DVT, or MI.