Jacob H. Bagley

Thrombin and hemin as central factors in the mechanisms of intracerebral hemorrhage–induced secondary brain injury and as potential targets for intervention

Intracerebral hemorrhage (ICH) is a subtype of stoke that may cause significant morbidity and mortality. Brain injury due to ICH initially occurs within the first few hours as a result of mass effect due to hematoma formation. However, there is increasing interest in the mechanisms of secondary brain injury as many patients continue to deteriorate clinically despite no signs of rehemorrhage or hematoma expansion. This continued insult after primary hemorrhage is believed to be mediated by the cytotoxic, excitotoxic, oxidative, and inflammatory effects of intraparenchymal blood. The main factors responsible for this injury are thrombin and erythrocyte contents such as hemoglobin. Therapies including thrombin inhibitors, N-methyl-D-aspartate antagonists, chelators to bind free iron, and antiinflammatory drugs are currently under investigation for reducing this secondary brain injury. This review will discuss the molecular mechanisms of brain injury as a result of intraparenchymal blood, potential targets for therapeutic intervention, and treatment strategies currently in development.

Vestibular schwannomas in the modern era: epidemiology, treatment trends, and disparities in management.

OBJECT There are a variety of treatment options for the management of vestibular schwannomas (VSs), including microsurgical resection, radiotherapy, and observation. Although the choice of treatment is dependent on various patient factors, physician bias has been shown to significantly affect treatment choice for VS. In this study the authors describe the current epidemiology of VS and treatment trends in the US in the modern era. They also illustrate patient and tumor characteristics and elucidate their effect on tumor management. METHODS Patients diagnosed with VS were identified through the Surveillance, Epidemiology, and End Results database, spanning the years 2004-2009. Age-adjusted incidence rates were calculated and adjusted using the 2000 US standard population. The chi-square and Student t-tests were used to evaluate differences between patient and tumor characteristics. Multivariate logistic regression was performed to determine the effects of various patient and tumor characteristics on the choice of tumor treatment. RESULTS A total of 6225 patients with VSs treated between 2004 and 2009 were identified. The overall incidence rate was 1.2 per 100,000 population per year. The median age of patients with VS was 55 years, with the majority of patients being Caucasian (83.16%). Of all patients, 3053 (49.04%) received surgery only, with 1466 (23.55%) receiving radiotherapy alone. Both surgery and radiation were only used in 123 patients (1.98%), with 1504 patients not undergoing any treatment (24.16%). Increasing age correlated with decreased use of surgery (OR 0.95, 95% CI 0.95-0.96; p<0.0001), whereas increasing tumor size was associated with the increased use of surgery (OR 1.04, 95% CI 1.04-1.05; p<0.0001). Older age was associated with an increased likelihood of conservative management (OR 1.04, 95% CI 1.04-1.05; p<0.0001). Racial disparities were also seen, with African American patients being significantly less likely to receive surgical treatment compared with Caucasians (OR 0.50, 95% CI 0.35-0.70; p<0.0001), despite having larger tumors at diagnosis. CONCLUSIONS The incidence of vestibular schwannomas in the US is 1.2 per 100,000 population per year. Although many studies have demonstrated improved outcomes with the use of radiotherapy for small- to medium-sized VSs, surgery is still the most commonly used treatment modality for these tumors. Racial disparities also exist in the treatment of VSs, with African American patients being half as likely to receive surgery and nearly twice as likely to have their VSs managed conservatively despite presenting with larger tumors. Further studies are needed to elucidate the reasons for treatment disparities and investigate the nationwide trend of resection for the treatment of small VSs.

Cancer after spinal fusion: the role of bone morphogenetic protein.

BACKGROUND Bone morphogenetic protein (BMP) is used in tens of thousands of spinal fusions each year. A trial evaluating a high-dose BMP formulation demonstrated that its use may be associated with an increased risk of cancer. OBJECTIVE To evaluate whether BMP, as commonly used today, is associated with an increased risk of cancer or benign tumors. METHODS We performed a retrospective study using the Thomson Reuter MarketScan database. We retained all patients who had no previous diagnosis of cancer or benign tumor and had at least 2 years of uninterrupted enrollment in the database before and after their operations. A propensity score--matched cohort was created to ensure greater covariate balance between treatment groups. RESULTS Within the propensity score--matched cohort (n = 4698), BMP-exposed patients had a nonsignificant increase in the rate of cancer diagnosis (9.37% vs 7.92%; P = .08). After adjustment for covariates, BMP exposure was associated with a 31% increased risk of benign tumor diagnosis (odds ratio, 1.31; 95% confidence interval, 1.02-1.68; P < .05). When the benign tumor diagnoses were stratified by organ type, BMP patients had significantly more diagnoses of benign nervous system tumors (0.81% vs 0.34%; P = .03), and within this group, benign tumors of the spinal meninges were much more common in the BMP-treated group (0.13% vs 0.02%; P = .002). CONCLUSION The results of this large, independent, propensity-matched study suggest that the use of BMP in lumbar fusions is associated with a significantly higher rate of benign neoplasms but not malignancies.

Racial disparities in outcomes of spinal surgery for lumbar stenosis.

Study Design. A retrospective, cross-sectional study. Objective. To evaluate racial disparities in outcomes of lumbar stenosis surgery. Summary of Background Data. Racial inequalities have been described in the outcomes of cardiovascular and orthopedic procedures. There have been minimal investigation of racial disparities in complications and costs of lumbar laminectomies and fusions. Methods. We analyzed the Medicaid data set of Thomson Reuters MarketScan database. African-American and non-Hispanic white patients who underwent laminectomy or fusion for lumbar stenosis with at least 2 years postoperative data were included. We examined the effect of race on the rate of reoperations, complications, and the cost associated with surgery. Results. African-American patients in the Medicaid database were at no higher risk for reoperation in the 2 years after an operation for lumbar stenosis than white patients (7.14% vs. 7.89%, P = 0.7895). However, we did find that African-American patients were more likely to experience postoperative complications of any kind, even after adjusting for length of hospital stay, comorbidities, sex, and age (adjusted odds ratio = 1.819, P = 0.0123 for immediate complication; adjusted odds ratio = 1.746, P = 0.0141 for 30-d complication; and adjusted odds ratio = 1.611, P = 0.0410 for 90-d complication). White patients had a significantly shorter length of stay (3 vs. 5 d, P < 0.007) and accrued fewer hospital-related costs (

Utilization of spinal cord stimulation in patients with failed back surgery syndrome.

16,148 vs.

Disparities in the outcomes of lumbar spinal stenosis surgery based on insurance status.

24,267, P < 0.0007). African-American patients, despite having more comorbidities in our sample, were prescribed significantly fewer medications in the 2 years after index procedures (91 vs. 138 prescriptions, P < 0.0007) and had fewer medication costs during the 2 years after surgery (

Low-grade astrocytomas: the prognostic value of fibrillary, gemistocytic, and protoplasmic tumor histology

5297 vs.

Arachnoiditis ossificans of the thoracic spine

8450, P < 0.0007). Conclusion. At the national level, there are several racial disparities in the rate of complications, length of stay, and costs after surgery for lumbar spinal stenosis. Level of Evidence: 3

Giant, Completely Calcified Lumbar Juxtafacet Cyst: Report of an Unusual Case:

Study Design. Retrospective analysis of a population-based insurance claims data set. Objective. To evaluate the use of spinal cord stimulation (SCS) and lumbar reoperation for the treatment of failed back surgery syndrome (FBSS), and examine their associated complications and health care costs. Summary of Background Data. FBSS is a major source of chronic neuropathic pain and affects up to 40% of patients who undergo lumbosacral spine surgery for back pain. Thus far, few economic analyses have been performed comparing the various treatments for FBSS, with these studies involving small sample sizes. In addition, the nationwide practices in the use of SCS for FBSS are unknown. Methods. The MarketScan data set was used to analyze patients with FBSS who underwent SCS or spinal reoperation between 2000 and 2009. Propensity score methods were used to match patients who underwent SCS with those who underwent lumbar reoperation to examine health care resource utilization. Postoperative complications were analyzed with multivariate logistic regression. Health care use was analyzed using negative binomial and general linear models. Results. The study cohort included 16,455 patients with FBSS, with 395 undergoing SCS implantation (2.4%). Complication rates at 90 days were significantly lower for SCS than spinal reoperation (P < 0.0001). Also in the matched cohort, hospital stay (P < 0.0001) and associated charges (P = 0.016) were lower for patients with SCS. However outpatient, emergency room, and medication charges were similar between the 2 groups. Overall cost totaling

Improved survival in the largest national cohort of adults with cerebellar versus supratentorial low-grade astrocytomas

82,586 at 2 years was slightly higher in the lumbar reoperation group than in the SCS group with total cost of