S. Harrison Farber

The Incidence of Spinal Cord Injury in Implantation of Percutaneous and Paddle Electrodes for Spinal Cord Stimulation

Spinal cord stimulation (SCS) has been proven effective for multiple chronic pain syndromes. Over the past 40 years of use, the complication rates of SCS have been well defined in the literature; however, the incidence of one of the most devastating complications, spinal cord injury (SCI), remains largely unknown. The goal of the study was to quantify the incidence of SCI in both percutaneous and paddle electrode implantation.

Prospect of rindopepimut in the treatment of glioblastoma

ABSTRACT Introduction: Rindopepimut (CDX-110) is a peptide vaccine that targets epidermal growth factor receptor variant III (EGFRvIII), a tumor-specific epitope expressed in the most common and lethal primary malignant neoplasm of the brain – glioblastoma (GBM). Areas covered: The EGFRvIII mutation introduces an 801 base pair in-frame deletion of the extracellular domain of the transmembrane tyrosine kinase, resulting in constitutive kinase activity, amplification of cell growth, and inhibition of apoptosis. Rindopepimut contains a 14mer amino acid peptide spanning the EGFRvIII mutation site that is conjugated to keyhole limpet hemocyanin (KLH). The EGFRvIII neoantigen is exclusively present on GBM cells, providing rindopepimut tumor-specific activity. The authors review rindopepimut’s clinical efficacy, administration, safety, and prospects in the treatment of GBM. Expert opinion: Rindopepimut showed clinical benefit and significant efficacy in phase II clinical trials, including as part of a multi-immunotherapy approach. A phase III clinical trial was terminated early, however, as it was deemed likely the study would fail to meet its primary endpoint. Longer term and sub-group analyses will be necessary to better understand rindopepimut’s future role in GBM therapy.

Impact of Increasing Age on Outcomes of Spinal Fusion in Adult Idiopathic Scoliosis.

OBJECTIVE To investigate the role of advancing age on postoperative complications and revision surgery after fusion for scoliosis. METHODS A retrospective, cohort study was performed using the Thomson Reuters MarketScan database, examining patients with adult scoliosis who underwent spinal fusion from 2000 to 2009. Primary outcomes included infection, hemorrhage and pulmonary embolism (PE) within 90 days of surgery, and refusion. The effect of increasing age was estimated using the odds ratio (OR) of complications in a multivariate logistic regression analysis, and a Cox proportional hazard model estimated the hazard ratio of refusion. RESULTS A total of 8432 patients were included in this study. Overall, the average age was 53.3 years, with 26.90% males and 39% with a Charlson Comorbidity Score of ≥ 1. Most patients had commercial insurance (66.81%), with 26.03% and 7.16% covered by Medicare and Medicaid, respectively. Increasing age (per 5-year increment) was a significant predictor of hemorrhagic complication (OR, 1.06; confidence interval [CI], 1.01-1.11; P = 0.0196), PE (OR, 1.09; CI, 1.03-1.16; P = 0.0031), infection (OR, 1.04; CI, 1.01-1.07; P = 0.0053), and refusion (hazard ratio, 1.07; CI, 1.02-1.13; P = 0.0103). CONCLUSIONS In this study, age was associated with increased risk of hemorrhage, PE, infection, and refusion. With the aging population, the role of patient age on postoperative healing and outcomes deserves deeper investigation after repair of adult idiopathic scoliosis.

Comparison of Bilateral vs. Staged Unilateral Deep Brain Stimulation (DBS) in Parkinson's Disease in Patients Under 70 Years of Age

The most popular surgical method for deep brain stimulation (DBS) in Parkinsons disease (PD) is simultaneous bilateral DBS. However, some centers conduct a staged unilateral approach advocating that reduced continuous intraoperative time reduces postoperative complications, thus justifying the cost of a second operative session. To test these assumptions, we performed a retrospective analysis of the Truven Health MarketScan® Database.

Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors

T cell dysfunction contributes to tumor immune escape in patients with cancer and is particularly severe amidst glioblastoma (GBM). Among other defects, T cell lymphopenia is characteristic, yet often attributed to treatment. We reveal that even treatment-naïve subjects and mice with GBM can harbor AIDS-level CD4 counts, as well as contracted, T cell–deficient lymphoid organs. Missing naïve T cells are instead found sequestered in large numbers in the bone marrow. This phenomenon characterizes not only GBM but a variety of other cancers, although only when tumors are introduced into the intracranial compartment. T cell sequestration is accompanied by tumor-imposed loss of S1P1 from the T cell surface and is reversible upon precluding S1P1 internalization. In murine models of GBM, hindering S1P1 internalization and reversing sequestration licenses T cell–activating therapies that were previously ineffective. Sequestration of T cells in bone marrow is therefore a tumor-adaptive mode of T cell dysfunction, whose reversal may constitute a promising immunotherapeutic adjunct.Patients with glioblastoma experience lymphopenia and sequestration of T cells in the bone marrow, which is recapitulated in mice with brain tumors, where the reversible nature of this effect is demonstrated by an approach that enables the efficacy of other immunotherapeutics.

Biopsy of enlarging lesions after stereotactic radiosurgery for brain metastases frequently reveals radiation necrosis

Background Stereotactic radiosurgery (SRS) offers excellent local control for brain metastases (BM) with low rates of toxicity. Radiation necrosis (RN) may occur after treatment and is challenging to distinguish from local recurrence (LR). We evaluated enlarging brain lesions following SRS that were subsequently biopsied to differentiate RN versus LR. Methods This study reviewed patients receiving SRS for BM between 2008 and 2012 who underwent a biopsy for suspicion of RN versus LR on MRI. Data collection included demographics, radiation parameters, imaging findings, and post-biopsy pathology. Kaplan-Meier methods determined overall survival. Fishers exact test assessed for association between lesion biopsy result and variables of interest. Results Thirty-four patients with 35 biopsied BM were included. Lesions were biopsied a median of 8.8 months after SRS. Most patients had primary lung cancer (11; 31.4%). Eleven (31.4%) biopsies were positive for LR and 24 (68.6%) showed RN only. Median overall survival was longer for patients with RN (31.0 mo) than for patients with LR (14.5 mo; P = 0.135). Time from SRS to biopsy was significantly different between RN and LR groups; 10 lesions (52.5%) biopsied ≤9 months after SRS showed LR, whereas 1 lesion (6.3%) biopsied >9 months after SRS showed LR (P = 0.004). For 16 (65.7%) lesions, management was changed or directed by the biopsy results. Conclusions Stereotactic biopsy for accessible enlarging lesions after SRS appears diagnostically valuable in patients with few lesions and changes clinical management. RN should be suspected in patients with an enlarging lesion more than 9 months post-SRS.

Embracing rejection: Immunologic trends in brain metastasis

ABSTRACT Brain metastases represent the most common type of brain tumor. These tumors offer a dismal prognosis and significantly impact quality of life for patients. Their capacity for central nervous system (CNS) invasion is dependent upon induced disruptions to the blood–brain barrier (BBB), alterations to the brain microenvironment, and mechanisms for escaping CNS immunosurveillance. In the emerging era of immunotherapy, understanding how metastases are influenced by the immunologic peculiarities of the CNS will be crucial to forging therapeutic advances. In this review, the immunology of brain metastasis is explored.

The Safety of available immunotherapy for the treatment of glioblastoma

ABSTRACT Introduction: Glioblastoma (GBM) is the most common malignant primary brain tumor in adults. Current standard of care involves maximal surgical resection combined with adjuvant chemoradiation. Growing support exists for a role of immunotherapy in treating these tumors with the goal of targeted cytotoxicity. Here we review data on the safety for current immunotherapies being tested in GBM. Areas covered: Safety data from published clinical trials, including ongoing clinical trials were reviewed. Immunotherapeutic classes currently under investigation in GBM include various vaccination strategies, adoptive T cell immunotherapy, immune checkpoint blockade, monoclonal antibodies, and cytokine therapies. Trials include children, adolescents, and adults with either primary or recurrent GBM. Expert opinion: Based on the reviewed clinical trials, the current immunotherapies targeting GBM are safe and well-tolerated with minimal toxicities which should be noted. However, the gains in patient survival have been modest. A safe and well-tolerated combinatory immunotherapeutic approach may be essential for optimal efficacy towards GBM.

Do obese patients have worse outcomes after direct lateral interbody fusion compared to non-obese patients?

Obese patients undergoing lumbar spinal fusion surgery are a challenge to the operating surgeon. Direct lateral interbody fusion (DLIF) has been performed for degenerative disease of the lumbar spine with good outcomes; nevertheless, how obese patients fare compared to non-obese patients after DLIF remains unknown. The primary aim of this study is to compare rates of postoperative complications and long-term outcomes between obese and non-obese patients undergoing DLIF. Sixty-three patients (obese: 29, non-obese: 34) undergoing index DLIF for degenerative disease of the spine between 2010 and 2012 at our institution were retrospectively enrolled. We analyzed data on demographics, postoperative complications, back and leg pain, and functional disability over 2 years. Patients completed the Oswestry Disability Index (ODI) and Visual Analog Scale (VAS) back and leg pain numerical rating scores before surgery, then at 12 and 24 months after surgery. Outcomes and complication rates were compared between the cohorts. The cohorts were similar at baseline. Postoperative complications rates were similar between obese and non-obese patients. There was no statistically significant difference in the incidence of durotomy (p=0.91), anterior thigh numbness (p=0.60), cerebrospinal fluid leak (p=0.91), postoperative infection (p=0.37), or bleeding requiring transfusion (p=0.16). No patient experienced a nerve injury or psoas hematoma. Both cohorts had similar 2 year improvement in VAS for back pain, leg pain, and ODI. Our study demonstrates that obese and non-obese patients undergoing DLIF have similar complication profiles; hence, a patients weight should not be a contraindication to DLIF.

Comparing outcomes of early, late, and non-surgical management of intraspinal abscess

Intraspinal abscesses (ISAs) are rare lesions that are often neurologically devastating. Current treatment paradigms vary widely including early surgical decompression, drainage, and systemic antibiotics, delayed surgery, and sole medical management. The National Inpatient Sample (NIS) database was queried for cases of ISA from 2003 to 2012. Early and late surgery were defined as occurring before or after 48h of admission. Outcome measures included mortality, incidence of major complications, length of stay (LOS), and inpatient costs. A total of 10,150 patients were included (6281 early surgery, 3167 delayed surgery, 702 medical management). Paralysis, the main comorbidity, was most associated with early surgery (p<0.0001). In multivariate analysis, the rates of postoperative infection and paraplegia were highest with early surgery (p<0.0001), but the incidence of sepsis was higher with delayed surgery (p<0.0001). Early surgery was least associated with in-hospital mortality (p=0.0212), sepsis (p<0.001), and had the shortest LOS (p<0.001). Charges were highest with delayed surgery, and least with medical management (p<0.001). Medical management was associated with lower rates of complications (p<0.001). This is the largest study of patients with ISAs ever performed. Our results suggest that patients with ISAs undergoing surgical management have better outcomes and lower costs when operated on within 48h of admission, emphasizing the importance of accurate and early diagnosis of ISA.