Ranjith Babu

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.

2012 Young Investigator Award winner: The distribution of body mass as a significant risk factor for lumbar spinal fusion postoperative infections.

Study Design. A retrospective review. Objective. The purpose of this study was to determine the role in body habitus and weight distribution on developing a surgical site infection (SSI). Summary of Background Data. SSI after lumbar spine surgery remains a significant cause of morbidity. The literature demonstrates an increased risk of postoperative infections associated with obesity, diabetes, and multilevel surgeries. Methods. A retrospective review was performed on a consecutive cohort of 298 adult patients who underwent lumbar spine fusion surgeries between 2006 and 2008 at the Duke University Medical Center. Previously identified risk factors (i.e., number of levels, diabetes, body mass index [BMI]) were collected, as well as the horizontal distance from the lamina to the skin surface (measured at L4) and thickness of subcutaneous fat at the surgical site. Results. Among the 298 patients, 24 (8%) had postoperative infections. Of the previously identified risk factors, number of levels (P = 0.0078) was found to be significantly associated with infections, whereas BMI (P = 0.16) and diabetes (P = 0.13) were found not to be statistically significant. Obesity (BMI ≥30) (P = 0.025), skin to lamina distance (P = 0.046), and thickness of the subcutaneous fat (P = 0.035) were found to be significant risk factors for SSI. Conclusion. Our findings suggest that in obese patients, the distribution of body mass is more predictive of SSI than the absolute BMI and deserves attention in preoperative evaluation.

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.

Rindopepimut: an evidence-based review of its therapeutic potential in the treatment of EGFRvIII-positive glioblastoma

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults and is universally fatal. Despite surgical resection, radiotherapy, and systemic chemotherapy, the median overall survival is less than 15 months. As current therapies are not tumor-specific, treatment commonly results in toxicity. The epidermal growth factor receptor variant III (EGFRvIII) is a naturally occurring mutant of EGFR and is expressed on approximately 20% to 30% of GBMs. As it is not expressed on normal cells, it is an ideal therapeutic target. Rindopepimut is a peptide vaccine which elicits EGFRvIII-specific humoral and cellular immune responses. Phase I and II clinical trials have demonstrated significantly higher progression-free and overall survival times in vaccinated patients with EGFRvIII-expressing GBM tumors. Side effects are minimal and mainly consist of hypersensitivity reactions. Due to the efficacy and safety of rindopepimut, it is a promising therapy for patients with GBM. Currently, rindopepimut is undergoing clinical testing in an international Phase III trial for newly diagnosed GBM and a Phase II trial for relapsed GBM.

Thickness of subcutaneous fat as a risk factor for infection in cervical spine fusion surgery.

BACKGROUND Surgical site infections increase the incidence of morbidity and mortality as well as health-care expenses. The cost of care increases threefold to fourfold as a consequence of surgical site infection after spinal surgery. The aim of the present study was to determine the role of subcutaneous fat thickness in the development of surgical site infection following cervical spine fusion surgery. METHODS We performed a retrospective review of a consecutive cohort of 213 adult patients who underwent posterior cervical spine fusion between 2006 and 2008 at Duke University Medical Center. The horizontal distance from the lamina to the skin surface at the C5 level and the thickness of subcutaneous fat were measured, and the ratio of the fat thickness to the total distance at the surgical site was determined. Previously identified risk factors for the development of surgical site infection were also recorded. RESULTS Twenty-two of the 213 patients developed a postoperative infection. Obesity (body mass index ≥ 30 kg/m2) was not a significant risk factor for surgical site infection; the body mass index (and 95% confidence interval) was 29.4 ± 1.2 kg/m2 in the patients who developed a surgical site infection compared with 28.9 ± 0.94 kg/m2 in the patients without an infection. However, the thickness of subcutaneous fat and the ratio of the fat thickness to the lamina-to-skin distance were both significant risk factors for infection. The thickness of subcutaneous fat was 27.0 ± 2.5 mm in the patients who developed a surgical site infection group compared with 21.4 ± 0.88 mm in the patients without an infection (p = 0.042). The ratio of fat thickness to total thickness was 0.42 ± 0.019 in the patients who developed a surgical site infection compared with 0.35 ± 0.01 in the patients without an infection (p = 0.020). Multivariate analysis revealed this ratio to be an independent risk factor for developing a postoperative infection (odds ratio, 3.18; 95% confidence interval, 1.02 to 9.97). CONCLUSIONS The study demonstrated that the thickness of subcutaneous fat at the surgical site is a factor in the development of surgical site infection following cervical spine fusion and deserves assessment in the preoperative evaluation.

Spinal surgery: variations in health care costs and implications for episode-based bundled payments.

Study Design. Retrospective, observational. Objective. To simulate what episodes of care in spinal surgery might look like in a bundled payment system and to evaluate the associated costs and characteristics. Summary of Background Data. Episode-based payment bundling has received considerable attention as a potential method to help curb the rise in health care spending and is being investigated as a new payment model as part of the Affordable Care Act. Although earlier studies investigated bundled payments in a number of surgical settings, very few focused on spine surgery, specifically. Methods. We analyzed data from MarketScan. Patients were included in the study if they underwent cervical or lumbar spinal surgery during 2000–2009, had at least 2-year preoperative and 90-day postoperative follow-up data. Patients were grouped on the basis of their diagnosis-related group (DRG) and then tracked in simulated episodes-of-care/payment bundles that lasted for the duration of 30, 60, and 90 days after the discharge from the index-surgical hospitalization. The total cost associated with each episode-of-care duration was measured and characterized. Results. A total of 196,918 patients met our inclusion criteria. Significant variation existed between DRGs, ranging from

Morbidity, mortality, and health care costs for patients undergoing spine surgery following the ACGME resident duty-hour reform: Clinical article.

11,180 (30-day bundle, DRG 491) to

Worse outcomes for patients undergoing brain tumor and cerebrovascular procedures following the ACGME resident duty-hour restrictions.

107,642 (30-day bundle, DRG 456). There were significant cost variations within each individual DRG. Postdischarge care accounted for a relatively small portion of overall bundle costs (range, 4%–8% in 90-day bundles). Total bundle costs remained relatively flat as bundle-length increased (total average cost of 30-day bundle:

Comparison of superior-level facet joint violations during open and percutaneous pedicle screw placement.

33,522 vs.