The Role of Kinase Signaling in Resistance to Bevacizumab Therapy for Glioblastoma Multiforme.

Glioblastoma multiforme (GBM) is the most malignant primary brain tumor and is characterized by vascular hyperplasia, necrosis, and high cell proliferation. Despite current standard therapies, including surgical resection and chemoradiotherapy, GBM patients survive for only about 15 months after diagnosis. Recently, the U.S. Food and Drug Administration (FDA) has approved an antiangiogenesis medication for recurrent GBM-bevacizumab-which has improved progression-free survival in GBM patients. Although bevacizumab has resulted in significant early clinical benefit, it inescapably predisposes tumor to relapse that can be represented as an infiltrative phenotype. Fundamentally, bevacizumab antagonizes the vascular endothelial growth factor A (VEGFA), which is consistently released on both endothelial cells (ECs) and GBM cells. Actually, VEGFA inhibition on the ECs leads to the suppression of vascular progression, permeability, and the vasogenic edema. However, the consequence of the VEGFA pathway blockage on the GBM cells remains controversial. Nevertheless, a piece of evidence supports the relationship between bevacizumab application and compensatory activation of kinase signaling within GBM cells, leading to a tumor cell invasion known as the main mechanism of bevacizumab-induced tumor resistance. A complete understanding of kinase responses associated with tumor invasion in bevacizumab-resistant GBMs offers new therapeutic opportunities. Thus, this study aimed at presenting a brief overview of preclinical and clinical data of the tumor invasion and resistance induced by bevacizumab administration in GBMs, with a focus on the kinase responses during treatment. The novel therapeutic strategies to overcome this resistance by targeting protein kinases have also been summarized.

Early detection of nonneurologic organ failure in patients with severe traumatic brain injury: Multiple organ dysfunction score or sequential organ failure assessment?

OBJECTIVE: The aim of this study is to compare the discriminant function of multiple organ dysfunction score (MODS) and sequential organ failure assessment (SOFA) components in predicting the Intensive Care Unit (ICU) mortality and neurologic outcome. MATERIALS AND METHODS: A descriptive-analytic study was conducted at a level I trauma center. Data were collected from patients with severe traumatic brain injury admitted to the neurosurgical ICU. Basic demographic data, SOFA and MOD scores were recorded daily for all patients. Odd's ratios (ORs) were calculated to determine the relationship of each component score to mortality, and area under receiver operating characteristic (AUROC) curve was used to compare the discriminative ability of two tools with respect to ICU mortality. RESULTS: The most common organ failure observed was respiratory detected by SOFA of 26% and MODS of 13%, and the second common was cardiovascular detected by SOFA of 18% and MODS of 13%. No hepatic or renal failure occurred, and coagulation failure reported as 2.5% by SOFA and MODS. Cardiovascular failure defined by both tools had a correlation to ICU mortality and it was more significant for SOFA (OR = 6.9, CI = 3.6-13.3, P < 0.05 for SOFA; OR = 5, CI = 3-8.3, P < 0.05 for MODS; AUROC = 0.82 for SOFA; AUROC = 0.73 for MODS). The relationship of cardiovascular failure to dichotomized neurologic outcome was not significant statistically. ICU mortality was not associated with respiratory or coagulation failure. CONCLUSION: Cardiovascular failure defined by either tool significantly related to ICU mortality. Compared to MODS, SOFA-defined cardiovascular failure was a stronger predictor of death. ICU mortality was not affected by respiratory or coagulation failures.

Anatomical Variations of Brachial Plexus in Adult Cadavers; A Descriptive Study.

BACKGROUND: Variations of the brachial plexus are common and a better awareness of the variations is of crucial importance to achieve successful results in its surgical procedures. The aim of the present study was to evaluate the anatomical variations of the brachial plexus in adult cadavers. METHODS: Bilateral upper limbs of 32 fresh cadavers (21 males and 11 females) consecutively referred to Guilan legal medicine organization from November 2011 to September 2014, were dissected and the trunks, cords and terminal nerves were evaluated. RESULTS: Six plexuses were prefixed in origin. The long thoracic nerve pierced the middle scalene muscle in 6 cases in the supra clavicular zone. The suprascapular nerve in 7 plexuses was formed from posterior division of the superior trunk. Five cadavers showed anastomosis between medial brachial cutaneous nerve and T1 root in the infra clavicular zone. Terminal branches variations were the highest wherein the ulnar nerve received a communicating branch from the lateral cord in 3 cases. The median nerve was formed by 2 lateral roots from lateral cord and 1 medial root from the medial cord in 6 cadavers. Some fibers from C7 root came to the musculocutaneous nerve in 8 cadavers. CONCLUSION: The correlation analysis between the variations and the demographic features was impossible due to the small sample size. The findings of the present study suggest a meta-analysis to assess the whole reported variations to obtain a proper approach for neurosurgeons.

Posttraumatic Temporal Bone Meningocele Presenting as a Cystic Mass in the External Auditory Canal.

INTRODUCTION: Temporal bone meningoencephalic herniation may occur in head trauma. It is a rare condition with potentially dangerous complications. Several different routes for temporal bone meningoencephalocele have been proposed. CLINICAL REPORT: An11-year-old boy with history of head trauma initially presented with a 9-months history of progressive right-sided hearing loss and facial weakness. The other complaint was formation of a cystic mass in the right external auditory canal. The patient underwent surgery via a mini middle cranial fossa craniotomy associated with a transmastoid approach. CONCLUSION: Although presenting symptoms can be subtle, early suspicion and confirmatory imaging aid in establishing the diagnosis. The combination of computed tomography and magnetic resonance imaging will help in proper preoperative diagnosis. The operation includes transmastoid, middle cranial fossa repair, or combination of both. The multilayer closure of bony defect is very important to avoid cerebrospinal fluid leak. Clinical manifestations, diagnosis, and surgical approaches for posttraumatic meningoencephaloceles arising in the head and neck region are briefly discussed.

Posterior lumbar interbody fusion and posterolateral fusion: Analogous procedures in decreasing the index of disability in patients with spondylolisthesis.

OBJECTIVE: The purpose of this study was to evaluate the disability in patients with spondylolisthesis who assigned either to posterolateral fusion (PLF) or posterior lumbar interbody fusion (PLIF) and to compare it between two groups. METHODS: In a prospective observational study, 102 surgical candidates with low-grade degenerative and isthmic spondylolisthesis enrolled from 2012 to 2014, and randomly assigned into two groups: PLF and PLIF. Evaluation of disability has been done by a questionnaire using Oswestry Disability Index (ODI). The questionnaire was completed by all patients before the surgery, the day after surgery, after 6 months and after 1-year. RESULTS: There were no statistically significant differences in terms of age and sex distribution and pre-operation ODI between groups (P > 0.05). Comparison of the mean ODI scores of two groups over the whole study period showed no significant statistical difference (P = 0.074). ODIs also showed no significant differences between two groups the day after surgery, 6(th) months and 1-year after surgery (P = 0.385, P = 0.093, P = 0.122 and P = 433) respectively. Analyzing the course of ODI over the study period, showed a significant descending pattern for either of groups (P < 0.0001). CONCLUSION: Both surgical fusion techniques (PLF and PLIF) were efficient to lessen the disability of patients with spondylolisthesis, and none of the fusion techniques were related to a better outcome in terms of disability.

Neuron-specific enolase and S100BB as outcome predictors in severe diffuse axonal injury.

BACKGROUND: Diffuse axonal injury (DAI) is a common type of traumatic brain injury, mostly associated with mild changes on computed tomography (CT) scan. Serum biomarkers might be used in the diagnosis and prognosis of this injury type. Our purpose was to determine temporal profile and predictive values of serum concentrations of protein S100BB and neuron-specific enolase (NSE) after DAI. METHODS: Twenty-eight isolated severe DAI patients (Glasgow Coma Scale score ≤ 8) with normal CT were enrolled in the study. Serum levels of S100BB and NSE were determined at 6 hours, 24 hours, 48 hours, and 72 hours after injury, using enzyme-linked immunosorbent assay. Clinical outcome variables of DAI comprised survival at discharge and Glasgow Outcome scale (GOS) after 3 months and also 2 years. RESULTS: S100BB concentration was maximum in 6 hours after injury (median = 280.75 ng/L) followed by a quick drop. Its value was significantly higher on third day in patients with unfavorable outcome (GOS score = 1-3) versus favorable outcome (GOS score = 4, 5) (p < 0.0001). The values of NSE had mild changes during 3 days; however, these measured values at 72 hours after trauma manifested higher in unfavorable outcome (p < 0.05). CONCLUSIONS: Increased serum concentrations of NSE and S100BB within first 3 days after DAI are associated with poor outcome despite mild CT findings. S100BB level at 72 hours after injury can predict late outcome in DAI patients. LEVEL OF EVIDENCE: Prognostic study, level III.

Effective factors on linguistic disorder during acute phase following traumatic brain injury in adults.

Traumatic brain injury (TBI) has been known to be the leading cause of breakdown and long-term disability in people under 45 years of age. This study highlights the effective factors on post-traumatic (PT) linguistic disorder and relations between linguistic and cognitive function after trauma in adults with acute TBI. A cross-sectional design was employed to study 60 post-TBI hospitalized adults aged 18-65 years. Post-traumatic (PT) linguistic disorder and cognitive deficit after TBI were respectively diagnosed using the Persian Aphasia Test (PAT) and Persian version of Mini-Mental State Examination (MMSE) at discharge. Primary post-resuscitation consciousness level was determined using the Glasgow Coma Scale (GCS). Paracilinical data was obtained by CT scan technique. Multiple logistic regression analysis illustrated that brain injury severity was the first powerful significant predictor of PT linguistic disorder after TBI and frontotemporal lesion was the second. It was also revealed that cognitive function score was significantly correlated with score of each language skill except repetition. Subsequences of TBI are more commonly language dysfunctions that demand cognitive flexibility. Moderate, severe and fronto-temporal lesion can increase the risk of processing deficit in linguistic macrostructure production and comprehension. The dissociation risk of cortical and subcortical pathways related to cognitive-linguistic processing due to intracranial lesions can augment possibility of lexical-semantic processing deficit in acute phase which probably contributes to later cognitive-communication disorder.