Donato Pacione

Decreased risk of wound infection after posterior cervical fusion with routine local application of vancomycin powder.

Study Design. A retrospective cohort study. Objective. To assess the ability of local vancomycin powder to prevent wound infection after posterior cervical fusion. Summary of Background Data. Wound infections are a significant source of morbidity and cost associated with spine surgery. Intraoperative application of vancomycin powder to the wound edges has been shown to lower the infection risk after posterior instrumented thoracolumbar fusion. There is little data on the efficacy and safety of local vancomycin powder in cervical spine surgery. Methods. All cases of posterior cervical fusion by a single surgeon were reviewed from 2007 to 2011. Routine application of 1 gram of vancomycin powder was started in August 2009. Baseline characteristics, operative details, and rates of wound infection and pseudarthrosis were compared between untreated patients and those who received vancomycin powder. Results. A total 171 patients underwent posterior cervical fusion between 2007 and 2011. Baseline and operative variables were similar between untreated patients (n = 92) and those who received vancomycin powder (n = 79). Patients were followed for a minimum of 1 year (range, 1.1–5.7 yr). The infection rate fell from 10.9% to 2.5% (P = 0.0384) following the introduction of vancomycin powder. The untreated and treated groups had similar rates of pseudarthrosis (5.4% vs. 5.1%). No complications attributable to vancomycin powder were identified. Conclusion. Routine local application of vancomycin powder is a low-cost effective strategy for preventing wound infection after posterior cervical fusion. Further studies are needed to optimize dosing, assess long-term safety, and evaluate use in other spinal operations. Level of Evidence: 2

Lumbar laminectomy and fusion with routine local application of vancomycin powder: decreased infection rate in instrumented and non-instrumented cases.

OBJECTIVE Wound infections are one of the most common and potentially devastating complications of spinal surgery. Intra-wound application of vancomycin powder has been shown to lower the infection risk following posterior instrumented fusion, but little evidence supports use in other spinal operations. The goal of this study is to assess the efficacy of vancomycin powder for lumbar laminectomy and fusion, both instrumented and non-instrumented. METHODS All cases of lumbar laminectomy and posterior fusion (with or without pedicle screw fixation) by a single surgeon were reviewed from 2007 to 2011. Routine application of 1g vancomycin powder was started in August 2009. Baseline characteristics and operative data were compared between untreated patients and those who received vancomycin powder. Rates of wound infection were compared for all fusions, and then separately for instrumented and non-instrumented cases. RESULTS 253 patients underwent lumbar laminectomy and fusion between 2007 and 2011. Baseline and operative variables were similar between untreated patients (n=97) and those who received vancomycin powder (n=156). Patients were followed for at least one year. The infection rate fell significantly following introduction of vancomycin powder (from 11% to 0%, p=0.000018). Subgroup analysis revealed significant infection reduction for both instrumented cases (from 12% to 0%, p=0.000806) and non-instrumented cases (from 10% to 0%, p=0.0496). No complications attributable to vancomycin powder were identified. CONCLUSION Local vancomycin powder appears to lower the risk of wound infection following lumbar laminectomy and fusion, both instrumented and non-instrumented. Further studies are needed to optimize dosing of vancomycin powder, assess long-term safety and efficacy, and evaluate use in other spinal operations.

Mutant IDH1 and seizures in patients with glioma

Objective: Because the d-2-hydroxyglutarate (D2HG) product of mutant isocitrate dehydrogenase 1 (IDH1mut) is released by tumor cells into the microenvironment and is structurally similar to the excitatory neurotransmitter glutamate, we sought to determine whether IDH1mut increases the risk of seizures in patients with glioma, and whether D2HG increases the electrical activity of neurons. Methods: Three WHO grade II-IV glioma cohorts from separate institutions (total N = 712) were retrospectively assessed for the presence of preoperative seizures and tumor location, WHO grade, 1p/19q codeletion, and IDH1mut status. Rat cortical neurons were grown on microelectrode arrays, and their electrical activity was measured before and after treatment with exogenous D2HG, in the presence or absence of the selective NMDA antagonist, AP5. Results: Preoperative seizures were observed in 18%–34% of IDH1 wild-type (IDH1wt) patients and in 59%–74% of IDH1mut patients (p < 0.001). Multivariable analysis, including WHO grade, 1p/19q codeletion, and temporal lobe location, showed that IDH1mut was an independent correlate with seizures (odds ratio 2.5, 95% confidence interval 1.6–3.9, p < 0.001). Exogenous D2HG increased the firing rate of cultured rat cortical neurons 4- to 6-fold, but was completely blocked by AP5. Conclusions: The D2HG product of IDH1mut may increase neuronal activity by mimicking the activity of glutamate on the NMDA receptor, and IDH1mut gliomas are more likely to cause seizures in patients. This has rapid translational implications for the personalized management of tumor-associated epilepsy, as targeted IDH1mut inhibitors may improve antiepileptic therapy in patients with IDH1mut gliomas.

The utility of a multimaterial 3D printed model for surgical planning of complex deformity of the skull base and craniovertebral junction.

Utilizing advanced 3D printing techniques, a multimaterial model was created for the surgical planning of a complex deformity of the skull base and craniovertebral junction. The model contained bone anatomy as well as vasculature and the previously placed occipital cervical instrumentation. Careful evaluation allowed for a unique preoperative perspective of the craniovertebral deformity and instrumentation options. This patient-specific model was invaluable in choosing the most effective approach and correction strategy, which was not readily apparent from standard 2D imaging. Advanced 3D multimaterial printing provides a cost-effective method of presurgical planning, which can also be used for both patient and resident education.

GPR133 (ADGRD1), an adhesion G-protein-coupled receptor, is necessary for glioblastoma growth.

Glioblastoma (GBM) is a deadly primary brain malignancy with extensive intratumoral hypoxia. Hypoxic regions of GBM contain stem-like cells and are associated with tumor growth and angiogenesis. The molecular mechanisms that regulate tumor growth in hypoxic conditions are incompletely understood. Here, we use primary human tumor biospecimens and cultures to identify GPR133 (ADGRD1), an orphan member of the adhesion family of G-protein-coupled receptors, as a critical regulator of the response to hypoxia and tumor growth in GBM. GPR133 is selectively expressed in CD133+ GBM stem cells (GSCs) and within the hypoxic areas of PPN in human biospecimens. GPR133 mRNA is transcriptionally upregulated by hypoxia in hypoxia-inducible factor 1α (Hif1α)-dependent manner. Genetic inhibition of GPR133 with short hairpin RNA reduces the prevalence of CD133+ GSCs, tumor cell proliferation and tumorsphere formation in vitro. Forskolin rescues the GPR133 knockdown phenotype, suggesting that GPR133 signaling is mediated by cAMP. Implantation of GBM cells with short hairpin RNA-mediated knockdown of GPR133 in the mouse brain markedly reduces tumor xenograft formation and increases host survival. Analysis of the TCGA data shows that GPR133 expression levels are inversely correlated with patient survival. These findings indicate that GPR133 is an important mediator of the hypoxic response in GBM and has significant protumorigenic functions. We propose that GPR133 represents a novel molecular target in GBM and possibly other malignancies where hypoxia is fundamental to pathogenesis.

Patient-Specific Screening Using High-Grade Glioma Explants to Determine Potential Radiosensitization by a TGF-β Small Molecule Inhibitor

High-grade glioma (HGG), a deadly primary brain malignancy, manifests radioresistance mediated by cell-intrinsic and microenvironmental mechanisms. High levels of the cytokine transforming growth factor-β (TGF-β) in HGG promote radioresistance by enforcing an effective DNA damage response and supporting glioma stem cell self-renewal. Our analysis of HGG TCGA data and immunohistochemical staining of phosphorylated Smad2, which is the main transducer of canonical TGF-β signaling, indicated variable levels of TGF-β pathway activation across HGG tumors. These data suggest that evaluating the putative benefit of inhibiting TGF-β during radiotherapy requires personalized screening. Thus, we used explant cultures of seven HGG specimens as a rapid, patient-specific ex vivo platform to test the hypothesis that LY364947, a small molecule inhibitor of the TGF-β type I receptor, acts as a radiosensitizer in HGG. Immunofluorescence detection and image analysis of γ-H2AX foci, a marker of cellular recognition of radiation-induced DNA damage, and Sox2, a stem cell marker that increases post-radiation, indicated that LY364947 blocked these radiation responses in five of seven specimens. Collectively, our findings suggest that TGF-β signaling increases radioresistance in most, but not all, HGGs. We propose that short-term culture of HGG explants provides a flexible and rapid platform for screening context-dependent efficacy of radiosensitizing agents in patient-specific fashion. This time- and cost-effective approach could be used to personalize treatment plans in HGG patients.

Cortical screw trajectory for instrumentation and fusion in the setting of osteopathic compression fracture allows for percutaneous kyphoplasty for adjacent level compression fractures

Spinal fixation in the osteoporotic patient can be challenging due to the poor trabecular bone quality of the vertebral body. Patients with osteoporotic vertebral body compression fractures are at risk for future compression fractures at adjacent levels, especially after cement augmentation. The purpose of this technical report is to describe the utilization of a cortical screw trajectory along with kyphoplasty for a patient with an osteoporotic compression fracture as well as degenerative spinal disease. This trajectory allows for the possibility of percutaneous pedicle access in the event of future compression fractures. Our patient underwent a decompressive laminectomy and kyphoplasty at the level of an osteoporotic compression fracture. The fracture was stabilized with cortical screw instrumentation and fusion at a level above and a level below the fracture. Subsequently the patient developed an adjacent level fracture within the fusion construct. Due to the utilization of a cortical screw trajectory for the initial fusion, the traditional pedicle trajectory was still accessible. As a result, the new fracture was treated with a percutaneous kyphoplasty through a standard pedicle trajectory. In conclusion, the use of a cortical screw trajectory for stabilization of osteoporotic compression fractures provides for a stronger bone screw interface and avoids osteoporotic trabecular vertebral body bone. At the same time this trajectory allows for future percutaneous pedicular access in the event that the patient suffers future compression fractures.

Antibiotic prophylaxis for subdural and subgaleal drains

OBJECTIVE The authors sought to determine the effects of eliminating the use of prolonged prophylactic systemic antibiotics (PPSAs) in patients with subdural and subgaleal drains. METHODS Using a retrospective database, the authors collected data for patients over the age of 17 years who had undergone cranial surgery at their institution between December 2013 and July 2014 (PPSAs period) or between December 2014 and July 2015 (non-PPSAs period) and had subdural or subgaleal drains left in place postoperatively. RESULTS One hundred five patients in the PPSAs period and 80 in the non-PPSAs period were identified. The discontinuation of PPSAs did not result in an increase in the frequency of surgical site infection (SSI). The frequency of Clostridium difficile (CDI) and the growth of resistant bacteria were reduced in the non-PPSAs period in comparison with the PPSAs period. In the 8 months after the drain prophylaxis protocol was changed,

Anaplastic pleomorphic xanthoastrocytoma with spinal leptomeningeal spread at the time of diagnosis in an adult

93,194.63 were saved in the costs of antibiotics and complications related to antibiotics. CONCLUSIONS After discontinuing PPSAs for patients with subdural or subgaleal drains at their institution, the authors did not observe an increase in the frequency of SSI. They did, however, note a decrease in the frequency of CDI and the growth of resistant organisms. It appears that not only can patients in this population do without PPSAs, but also that complications are avoided when antibiotic use is limited to 24 hours after surgery.

Coagulation abnormalities in children undergoing epilepsy surgery.

We describe the first patient, to our knowledge, with anaplastic pleomorphic xanthoastrocytoma (PXA) with spinal leptomeningeal spread at the time of diagnosis and present a review of the literature. PXA is a tumor that typically has an indolent course but occasionally, when anaplastic features are present, behaves in a more aggressive manner. We found that PXA with spinal leptomeningeal spread at the time of diagnosis confers a worse prognosis. Craniospinal imaging should be obtained at time of diagnosis of PXA and the presence of leptomeningeal spread may be indicative of a more aggressive disease process.