Anand Veeravagu

Risk Factors for Postoperative Spinal Wound Infections After Spinal Decompression and Fusion Surgeries

Study Design. This is a multivariate analysis of a prospectively collected database. Objective. To determine preoperative, intraoperative, and patient characteristics that contribute to an increased risk of postoperative wound infection in patients undergoing spinal surgery. Summary of Background Data. Current literature sites a postoperative infection rate of approximately 4%; however, few have completed multivariate analysis to determine factors which contribute to risk of infection. Methods. Our study identified patients who underwent a spinal decompression and fusion between 1997 and 2006 from the Veterans Affairs’ National Surgical Quality Improvement Program database. Multivariate logistic regression analysis was used to determine the effect of various preoperative variables on postoperative infection. Results. Data on 24,774 patients were analyzed. Wound infection was present in 752 (3.04%) patients, 287 (1.16%) deep, and 468 (1.89%) superficial. Postoperative infection was associated with longer hospital stay (7.12 vs. 4.20 days), higher 30-day mortality (1.06% vs. 0.5%), higher complication rates (1.24% vs. 0.05%), and higher return to the operating room rates (37% vs. 2.45%). Multivariate logistic regression identified insulin dependent diabetes (odds ratios [OR] = 1.50), current smoking (OR = 1.19) ASA class of 3 (OR = 1.45) or 4 to 5 (OR = 1.66), weight loss (OR = 2.14), dependent functional status (1.36) preoperative HCT <36 (1.37), disseminated cancer (1.83), fusion (OR = 1.24) and an operative duration of 3 to 6 hours (OR = 1.33) or >6 hours (OR = 1.40) as statistically significant predictors of postoperative infection. Conclusion. Using multivariate analysis of a large prospectively collected data from the National Surgical Quality Improvement Program database, we identified the most important risk factors for increased postoperative spinal wound infection. We have demonstrated the high mortality, morbidity, and hospitalization costs associated with postoperative spinal wound infections. The information provided should help alert clinicians to presence of these risks factors and the likelihood of higher postoperative infections and morbidity in spinal surgery patients.

Moyamoya disease in pediatric patients: outcomes of neurosurgical interventions

Neurosurgical interventions for moyamoya disease (MMD) in pediatric patients include direct, indirect, and combined revascularization procedures. Each technique has shown efficacy in the treatment of pediatric MMD; however, no single study has demonstrated the superiority of one technique over another. In this review, the authors explore the various studies focused on the use of these techniques for MMD in the pediatric population. They summarize the results of each study to clearly depict the clinical outcomes achieved at each institution that had utilized direct, indirect, or combined techniques. In certain studies, multiple techniques were used, and the clinical or radiological outcomes were compared accordingly. Direct techniques have been shown to aid a reduction in perioperative strokes and provide immediate revascularization to ischemic areas; however, these procedures are technically challenging, and not all pediatric patients are appropriate candidates. Indirect techniques have also shown efficacy in the pediatric population but may require a longer period for revascularization to occur and perfusion deficits to be reversed. The authors concluded that the clinical efficacy of one technique over another is still unclear, as most studies have had small populations and the same outcome measures have not been applied. Authors who compared direct and indirect techniques noted approximately equal clinical outcomes with differences in radiological findings. Additional, larger studies are needed to determine the advantages and disadvantages of the different techniques for the pediatric age group.

OUTCOMES AFTER REPEAT TRANSSPHENOIDAL SURGERY FOR RECURRENT CUSHING'S DISEASE

OBJECTIVETo systematically analyze patient outcomes after repeat transsphenoidal (TS) surgery for recurrent Cushings disease. METHODSWe retrospectively reviewed records of all patients with recurrent Cushings disease who underwent repeat TS surgery for resection of a pituitary corticotroph adenoma at the University of Virginia Medical Center from 1992 to 2006. Remission at follow-up was defined as a normal postoperative 24-hour urine free cortisol, or continued need for glucocorticoid replacement after repeat TS surgery. Recurrence of the disease was defined as an elevated 24-hour urine free cortisol with clinical symptoms consistent with Cushings disease while not receiving glucocorticoid replacement. Multivariate logistic regression was performed to evaluate the effect of potential predictors on remission. Recurrence rates, subsequent treatments, and the final endocrine status of the patients are presented. RESULTSWe identified 36 patients who underwent repeat TS surgery for recurrent Cushings disease. The mean age of the patients was 40.3 years (range, 17.1–63.0 yr), and 26 were women. The median time to recurrence after initial successful TS surgery was 36 months (range, 4 mo–16 yr). Remission after repeat TS surgery was observed in 22 (61%) of the 36 patients. During the same time period, of the 338 patients who underwent first-time TS surgery for Cushings disease, remission was achieved in 289 (85.5%). The odds of failure (to achieve remission) for patients with repeat TS surgery for recurrent Cushings disease were 3.7 times that of patients undergoing first-time TS surgery (odds ratio, 3.7; 95% confidence interval, 1.8–7.8). Two of the 22 patients with successful repeat TS surgery had a second recurrence at 6 and 11 months, respectively. Complete biochemical and clinical remission after stereotactic radiosurgery, adrenalectomy, and ongoing ketoconazole therapy was achieved in 30 (83.3%) of the 36 patients, and active disease continued in 6 patients (16.7%). CONCLUSIONAlthough the success of repeat TS surgery for recurrence of Cushings disease is less than that of initial surgery, a second procedure offers a reasonable possibility of immediate remission. If the operation is not successful, other treatments, including pituitary radiation, medical therapy, and even bilateral adrenalectomy, are required.

Craniotomy for resection of meningioma in the elderly: a multicentre, prospective analysis from the National Surgical Quality Improvement Program

Object Whether there is an increased surgical risk in elderly patients who undergo craniotomy for meningioma resection remains a point of controversy. Utilising multicentre, prospective data from the National Surgical Quality Improvement Program, the present study sought to address this controversy. Methods All patients who underwent a craniotomy for resection of intracranial meningioma (current procedural terminology codes 61512 and 61519) between 1997 and 2006 at 123 VA hospitals around the country were included. After controlling for preoperative factors such as ASA class, race, diabetes mellitus, disseminated cancer, tobacco use, tumour location and functional health status in a multivariate logistic regression model, the effect of elderly age (age greater than 70 years) on 30 day mortality was determined. Results Our study included 1281 patients who underwent surgical resection of an intracranial meningioma. Although each VA completed a different number of operations, we are able to provide case volume data for approximately 60 of the 123 hospitals. The elderly cohort represented 21.2% (n=258) of our total study population. Elderly patients had a higher 30 day mortality (12.0%) than younger subjects (4.6%) (p<0.0001). Similarly, elderly patients were more likely to have one or more complications (29.8% vs 13.1%, p<0.0001). Multivariate logistic regression identified age, functional status, preoperative disseminated cancer and tumour location as important predictors of 30 day mortality. After controlling for preoperative comorbidities and risk factors, the odds of perioperative mortality in elderly patients were three times that of younger patients (OR 3.0, 95% CI 1.7 to 5.3, p=0.0102). Conclusion After carefully controlling for various patient characteristics, ASA class and functional status, elderly patients have poorer outcome after surgical resection of intracranial meningioma than younger subjects.

Revision rates and complication incidence in single- and multilevel anterior cervical discectomy and fusion procedures: an administrative database study.

BACKGROUND CONTEXT The natural history of cervical degenerative disease with operative management has not been well described. Even with symptomatic and radiographic evidence of multilevel cervical disease, it is unclear whether single- or multilevel anterior cervical discectomy and fusion (ACDF) procedures produce superior long-term outcomes. PURPOSE To describe national trends in revision rates, complications, and readmission for patients undergoing single and multilevel ACDF. STUDY DESIGN Administrative database study. PATIENT SAMPLE Between 2006 and 2010, 92,867 patients were recorded for ACDF procedures in the Thomson Reuters MarketScan database. Restricting to patients with >24 months follow-up, 28,777 patients fulfilled our inclusion criteria, of which 12,744 (44%) underwent single-level and 16,033 (56%) underwent multilevel ACDFs. OUTCOME MEASURES Revision rates and postoperative complications. METHODS We used the MarketScan database from 2006 to 2010 to select ACDF procedures based on Current Procedural Terminology coding at inpatient visit. Outcome measures were ascertained using either International Classification of Disease version 9 or Current Procedural Terminology coding. RESULTS Perioperative complications were more common in multilevel procedures (odds ratio [OR], 1.4; 95% confidence interval [CI], 1.2-1.6; p<.0001). Single-level ACDF patients had higher rates of postoperative cervical epidural steroid injections (OR, 0.88; 95% CI, 0.8-1.0; p=.01). Within 30 days after index procedure, the multilevel ACDF cohort was 1.6 times more likely to have undergone revision (OR, 1.6; 95% CI, 1.1-2.4; p=.02). At 2 years follow-up, revision rates were 9.13% in the single-level ACDF cohort and 10.7% for multilevel ACDFs (OR, 1.2; 95% CI, 1.1-1.3; p<.0001). In a multivariate analysis at 2 years follow-up, patients from the multilevel cohort were more likely to have received a surgical revision (OR, 1.1; 95% CI, 1.0-1.2; p=.001), to be readmitted into the hospital for any cause (OR, 1.2; 95% CI, 1.1-1.4; p=.007), and to have suffered complications (OR, 1.3; 95% CI, 1.1-1.5; p=.0003). CONCLUSIONS In this study, we report rates of adverse events and the need for revision surgery in patients undergoing single versus multilevel ACDFs. Increasing number of levels fused at the time of index surgery correlated with increased rate of reoperations. Multilevel ACDF patients requiring additional surgery more often underwent more extensive revision surgeries.

Integrin αvβ3-Targeted Radioimmunotherapy of Glioblastoma Multiforme

Purpose: Abegrin is a monoclonal antibody to human integrin αVβ3, a cell adhesion molecule highly expressed on actively angiogenic endothelium and glioblastoma multiforme tumor cells. The purpose of this study was to evaluate the efficacy of a novel 90Y-Abegrin radioimmunotherapeutic agent in murine xenograft glioblastoma models with noninvasive in vivo molecular imaging modalities. Experimental Design: A s.c. U87MG human glioblastoma xenograft model was used to determine maximum tolerated dose (MTD), biodistribution, dose response, and efficacy of 90Y-Abegrin. Antitumor efficacy was also characterized in an orthotopic U87MG and in a HT-29 colorectal cancer model, a low integrin-expressing carcinoma. Small-animal positron emission tomography imaging was used to correlate histologic findings of treatment efficacy. Results: MTD and dose response analysis revealed 200 μCi per mouse as appropriate treatment dose with hepatic clearance and no organ toxicity. 90Y-Abegrin–treated U87MG tumor mice showed partial regression of tumor volume, with increased tumor volumes in 90Y-IgG, Abegrin, and saline groups. 18F-FDG imaging revealed a reduction of cell proliferation and metabolic activity whereas 18F-FLT reflected decreased DNA synthesis in the 90Y-Abegrin group. Ki67 analysis showed reduced proliferative index and quantitative terminal deoxynucleotidyl transferase dUTP nick-end labeling–positive analysis revealed increased DNA fragmentation and apoptosis in 90Y-Abegrin animals. CD31 and 4′,6-diamidino-2-phenylindole staining showed increased vascular fragmentation and dysmorphic vessel structure in 90Y-Abegrin animals only. Orthotopic U87MG tumors treated with 90Y-Abegrin displayed reduced tumor volume. HT-29 tumors showed no significant difference among the various groups. Conclusion: Radioimmunotherapy with 90Y-labeled Abegrin may prove promising in the treatment of highly vascular, invasive, and heterogeneous malignant brain tumors.

Vascular endothelial growth factor and vascular endothelial growth factor receptor inhibitors as anti-angiogenic agents in cancer therapy.

New blood vessel formation (angiogenesis) is fundamental to the process of tumor growth, invasion, and metastatic dissemination. The vascular endothelial growth factor (VEGF) family of ligands and receptors are well established as key regulators of these processes. VEGF is a glycoprotein with mitogenic activity on vascular endothelial cells. Specifically, VEGF-receptor pathway activation results in signaling cascades that promote endothelial cell growth, migration, differentiation, and survival from pre-existing vasculature. Thus, the role of VEGF has been extensively studied in the pathogenesis and angiogenesis of human cancers. Recent identification of seven VEGF ligand variants (VEGF [A-F], PIGF) and three VEGF tyrosine kinase receptors (VEGFR- [1-3]) has led to the development of several novel inhibitory compounds. Clinical trials have shown inhibitors to this pathway (anti-VEGF therapies) are effective in reducing tumor size, metastasis and blood vessel formation. Clinically, this may result in increased progression free survival, overall patient survival rate and will expand the potential for combinatorial therapies. Having been first described in the 1980s, VEGF patenting activity since then has focused on anti-cancer therapeutics designed to inhibit tumoral vascular formation. This review will focus on patents which target VEGF-[A-F] and/or VEGFR-[1-3] for use in anti-cancer treatment.

Integrin αvβ3 Antagonists for Anti-Angiogenic Cancer Treatment

Direct contact between cellular and extracellular matrix (ECM) proteins is necessary for a diverse array of physiologic processes including cellular activation, migration, proliferation, and differentiation. These direct interactions are modulated by cell adhesion molecules (CAMs) such as integrins, selectins, cadherins, and immunoglobulins. Integrin signaling also plays a key role in tumor growth, angiogenesis, and metastasis. Recent advances in the discovery and characterization of CAMs and their receptors, most notably integrin αvβ3, and the clarification of their roles in disease states have laid the groundwork for the development and clinical implementation of novel anti-cancer treatments. Integrin αvβ3 is a glycoprotein membrane receptor which recognizes ECM proteins expressing an arginine-glycine-aspartic acid (RGD) peptide sequence. The receptor is highly expressed on activated tumor endothelial cells, but not resting endothelial cells and normal organ systems, thus making αvβ3 an appropriate target for anti-angiogenic therapeutics. In addition, αvβ3 is also expressed on tumor cells, allowing for both tumor cell and tumor vasculature targeting of anti-integrin therapy. Throughout the past decade, numerous patents have been published and issued using αvβ3 antagonists for the prevention and/or treatment of cancer, with many antagonists demonstrating positive pre-clinical anti-angiogenic and anti-tumor results. This review will focus on the key points and distinguishing factors for patents which use antibodies, RGD peptides, non-RGD peptides, peptidomimetics, and amine salts as αvβ3 antagonists.

Acute Lung Injury in Patients with Subarachnoid Hemorrhage: A Nationwide Inpatient Sample Study

OBJECTIVE To determine national trends for patients with subarachnoid hemorrhage (SAH) and pulmonary complications including acute respiratory distress syndrome (ARDS). METHODS The Nationwide Inpatient Sample database was used to sample 193,209 admissions for SAH with and without ARDS during the period 1993-2008 using International Classification of Diseases, Ninth Revision, Clinical Modification coding. A multivariate stepwise regression analysis was performed. RESULTS The incidence of ARDS in patients with SAH increased from 35.51% in 1993 to 37.60% in 2008. However, the overall mortality in patients with SAH and in patients with SAH and ARDS decreased in the same period, from 42.30% to 31.99% and from 75.13% to 60.76%, respectively. Multivariate analysis showed that the predictors of developing ARDS in patients with SAH include older age; larger hospital size; and comorbidities such as epilepsy, cardiac arrest, sepsis, congestive heart failure, hypertension, chronic obstructive pulmonary disease, hematologic dysfunction, renal dysfunction, and neurologic dysfunction. Predictors of mortality in patients with SAH include age and hospital complications, such as coronary artery disease, ARDS, cancer, hematologic dysfunction, and renal dysfunction. CONCLUSIONS Patients with SAH are at increased risk of developing ARDS. The identification of certain risk factors may alert and aid practitioners in preventing worsening disease.

The role of radiosurgery in the treatment of craniopharyngiomas

The treatment of craniopharyngiomas is composed of an intricate balance of multiple modalities. Resection and radiotherapy have been combined to synergistically control tumor growth while preventing undue harm to crucial neurovascular structures. Although a craniopharyngioma is a benign lesion pathologically, it may induce severe neurological injury due to its location and rate of growth. More recently, the advent of targeted, fractionated radiotherapy has allowed for more aggressive tumor control while reducing the necessity for large resections. Initial studies have demonstrated significant tumor control in patients who are treated with resection combined with radiation therapy, versus surgery alone, with a lower rate of treatment-associated neurological deficits. In this review, a detailed account of the current studies evaluating the role of stereotactic radiosurgery in the management of craniopharyngiomas is presented. The authors also provide a short account of their experience to aid in defining the role of CyberKnife radiosurgery.