Refinement of intrathecal catheter design to enhance neuraxial distribution.

BACKGROUND: Delivery of therapeutics via indwelling intrathecal catheters is highly efficacious for targeting of pain, spasticity, neuraxial cancer and neurodegenerative disorders. However, current catheter designs have some major limitations. Given limited CSF flow, fixed intrathecal volume and the large distance of the rostro-caudal spinal axis, current intrathecal delivery routes fail to achieve adequate drug distribution. Additionally open catheter systems are plagued with cellular ingrowth and debris accumulation if used intermittently. NEW METHOD: RESULTS/COMPARISON WITH EXISTING METHOD(S): High speed imaging showed micro-valve catheters greatly increase fluid exit velocities compared to typical open-ended catheters, which prevents pooling of injectate proximal to the opening. When implanted intrathecally in rats, small injection volumes (7.5 µL) of dye or AAV9-RFP, resulted in an even rostro-caudal distribution along the spinal axis and robust transfection of neurons from cervical to lumbar dorsal root ganglia. In contrast, such injections with an open-ended catheter resulted in localized distribution and transfection proximal to the delivery site. Our poly micro-valve catheter design resulted in equivalent transfection rates of cervical DRG neurons using 100x lower titer of AAV9-RFP. Unlike open port catheters, no debris accumulation was observed in the lumen of implanted catheters, showing potential for long-term intermittent use. CONCLUSIONS: This catheter platform, suitable for small animal models is easily scalable for human use and addresses many of the problems observed with common catheter systems.

CD163+ macrophages monitor enhanced permeability at the blood-dorsal root ganglion barrier.

In dorsal root ganglia (DRG), macrophages reside close to sensory neurons and have largely been explored in the context of pain, nerve injury, and repair. However, we discovered that most DRG macrophages interact with and monitor the vasculature by sampling macromolecules from the blood. Characterization of the DRG vasculature revealed a specialized endothelial bed that transformed in molecular, structural, and permeability properties along the arteriovenous axis and was covered by macrophage-interacting pericytes and fibroblasts. Macrophage phagocytosis spatially aligned with peak endothelial permeability, a process regulated by enhanced caveolar transcytosis in endothelial cells. Profiling the DRG immune landscape revealed two subsets of perivascular macrophages with distinct transcriptome, turnover, and function. CD163+ macrophages self-maintained locally, specifically participated in vasculature monitoring, displayed distinct responses during peripheral inflammation, and were conserved in mouse and man. Our work provides a molecular explanation for the permeability of the blood-DRG barrier and identifies an unappreciated role of macrophages as integral components of the DRG-neurovascular unit.

Insights into FcγR involvement in pain-like behavior induced by an RA-derived anti-modified protein autoantibody.

Joint pain is one of the most debilitating symptoms of rheumatoid arthritis (RA) and patients frequently rate improvements in pain management as their priority. RA is hallmarked by the presence of anti-modified protein autoantibodies (AMPA) against post-translationally modified citrullinated, carbamylated and acetylated proteins. It has been suggested that autoantibody-mediated processes represent distinct mechanisms contributing to pain in RA. In this study, we investigated the pronociceptive properties of monoclonal AMPA 1325:01B09 (B09 mAb) derived from the plasma cell of an RA patient. We found that B09 mAb induces pain-like behavior in mice that is not associated with any visual, histological or transcriptional signs of inflammation in the joints, and not alleviated by non-steroidal anti-inflammatory drugs (NSAIDs). Instead, we found that B09 mAb is retained in dorsal root ganglia (DRG) and alters the expression of several satellite glia cell (SGC), neuron and macrophage-related factors in DRGs. Using mice that lack activating FcγRs, we uncovered that FcγRs are critical for the development of B09-induced pain-like behavior, and partially drive the transcriptional changes in the DRGs. Finally, we observed that B09 mAb binds SGC in vitro and in combination with external stimuli like ATP enhances transcriptional changes and protein release of pronociceptive factors from SGCs. We propose that certain RA antibodies bind epitopes in the DRG, here on SGCs, form immune complexes and activate resident macrophages via FcγR cross-linking. Our work supports the growing notion that autoantibodies can alter nociceptor signaling via mechanisms that are at large independent of local inflammatory processes in the joint.

Fibromyalgia patients with elevated levels of anti-satellite glia cell immunoglobulin G antibodies present with more severe symptoms.

ABSTRACT: Transferring fibromyalgia patient immunoglobulin G (IgG) to mice induces pain-like behaviour, and fibromyalgia IgG binds mouse and human satellite glia cells (SGCs). These findings suggest that autoantibodies could be part of fibromyalgia pathology. However, it is unknown how frequently fibromyalgia patients have anti-SGC antibodies and how anti-SGC antibodies associate with disease severity. Here, we quantified serum or plasma anti-SGC IgG levels in 2 fibromyalgia cohorts from Sweden and Canada using an indirect immunofluorescence murine cell culture assay. Fibromyalgia serum IgG binding to human SGCs in human dorsal root ganglia tissue sections was also assessed by immunofluorescence. In the cell culture assay, anti-SGC IgG levels were increased in both fibromyalgia cohorts compared with control group. Elevated anti-SGC IgG was associated with higher levels of self-reported pain in both cohorts, and higher fibromyalgia impact questionnaire scores and increased pressure sensitivity in the Swedish cohort. Anti-SGC IgG levels were not associated with fibromyalgia duration. Swedish fibromyalgia (FM) patients were clustered into FM-severe and FM-mild groups, and the FM-severe group had elevated anti-SGC IgG compared with the FM-mild group and control group. Anti-SGC IgG levels detected in culture positively correlated with increased binding to human SGCs. Moreover, the FM-severe group had elevated IgG binding to human SGCs compared with the FM-mild and control groups. These results demonstrate that a subset of fibromyalgia patients have elevated levels of anti-SGC antibodies, and the antibodies are associated with more severe fibromyalgia symptoms. Screening fibromyalgia patients for anti-SGC antibodies could provide a path to personalized treatment options that target autoantibodies and autoantibody production.

Odontoid Fracture as Proximal Junctional Failure in Patients With Multilevel Spine Fusions.

STUDY DESIGN: Retrospective study. OBJECTIVE: Proximal junctional failure (PJF) commonly occurs as a recognized potential outcome of fusion surgery. Here we describe a unique series of patients with multilevel spine fusion including the cervical spine, who developed PJF as an odontoid fracture. METHODS: We performed a single site retrospective review of patients with prior fusion that included a cervical component, who presented with an odontoid fracture between 2012 and 2019. Radiographic measurements included C2-C7 SVA, C2-C7 lordosis, T1 slope, Occiput-C2 angle, proximal junctional kyphosis, and cervical mismatch. Associated fractures, medical comorbidities, and treatments were determined via chart review after IRB approval. RESULTS: Nine patients met inclusion criteria. 5 reported trauma with subsequent onset of pain. All patients sustained a Type II odontoid fracture. 5 with associated C1/Jefferson fractures. In all patients, pre-injury Occiput-C2 angle was outside normative range; C2-C7 SVA was greater than 4 cm in 6 patients; T1-slope minus cervical lordosis was greater than 18.5 degrees in 6 patients. 7 patients were treated operatively with extension of fusion to C1 and 2 patients declined operative treatment. CONCLUSION: In this series of 9 patients with multilevel fusion with type II odontoid fractures, all patients demonstrated abnormal pre-fracture sagittal alignment parameters and a greater than normal association of C1 fractures was noted. Further study is needed to establish the role of poor sagittal alignment with compensatory occiput-C2 angulation as a predisposing factor for odontoid fracture as a proximal junctional failure mechanism.

Predicting Glioblastoma Cellular Motility from In Vivo MRI with a Radiomics Based Regression Model.

Characterizing the motile properties of glioblastoma tumor cells could provide a useful way to predict the spread of tumors and to tailor the therapeutic approach. Radiomics has emerged as a diagnostic tool in the classification of tumor grade, stage, and prognosis. The purpose of this work is to examine the potential of radiomics to predict the motility of glioblastoma cells. Tissue specimens were obtained from 31 patients undergoing surgical resection of glioblastoma. Mean tumor cell motility was calculated from time-lapse videos of specimen cells. Manual segmentation was used to define the border of the enhancing tumor T1-weighted MR images, and 107 radiomics features were extracted from the normalized image volumes. Model parameter coefficients were estimated using the adaptive lasso technique validated with leave-one-out cross validation (LOOCV) and permutation tests. The R-squared value for the predictive model was 0.60 with p-values for each individual parameter estimate less than 0.0001. Permutation test models trained with scrambled motility failed to produce a model that out-performed the model trained on the true data. The results of this work suggest that it is possible for a quantitative MRI feature-based regression model to non-invasively predict the cellular motility of glioblastomas.

DRGquant: A new modular AI-based pipeline for 3D analysis of the DRG.

BACKGROUND: The dorsal root ganglion (DRG) is structurally complex and pivotal to systems processing nociception. Whole mount analysis allows examination of intricate microarchitectural and cellular relationships of the DRG in three-dimensional (3D) space. NEW METHOD: We present DRGquant a set of tools and techniques optimized as a pipeline for automated image analysis and reconstruction of cells/structures within the DRG. We have developed an open source software pipeline that utilizes machine learning to identify substructures within the DRG and reliably classify and quantify them. RESULTS: Our methods were sufficiently sensitive to isolate, analyze, and classify individual DRG substructures including macrophages. The activation of macrophages was visualized and quantified in the DRG following intrathecal injection of lipopolysaccharide, and in a model of chemotherapy induced peripheral neuropathy. The percent volume of infiltrating macrophages was similar to a commercial source in quantification. Circulating fluorescent dextran was visualized within DRG macrophages using whole mount preparations, which enabled 3D reconstruction of the DRG and DRGquant demonstrated subcellular spatial resolution within individual macrophages. COMPARISON WITH EXISTING METHOD(S): Here we describe a reliable and efficient methodologic pipeline to prepare cleared and whole mount DRG tissue. DRGquant allows automated image analysis without tedious manual gating to reduce bias. The quantitation of DRG macrophages was superior to commercial solutions. CONCLUSIONS: Using machine learning to separate signal from noise and identify individual cells, DRGquant enabled us to isolate individual structures or areas of interest within the DRG for a more granular and fine-tuned analysis. Using these 3D techniques, we are better able to appreciate the biology of the DRG under experimental inflammatory conditions.

Acute failure of S2-alar-iliac screw pelvic fixation in adult spinal deformity: novel failure mechanism, case series, and review of the literature.

OBJECTIVE: Pelvic fixation with S2-alar-iliac (S2AI) screws is an established technique in adult deformity surgery. The authors' objective was to report the incidence and risk factors for an underreported acute failure mechanism of S2AI screws. METHODS: The authors retrospectively reviewed a consecutive series of ambulatory adults with fusions extending 3 or more levels, and which included S2AI screws. Acute failure of S2AI screws was defined as occurring within 6 months of the index surgery and requiring surgical revision. RESULTS: Failure occurred in 6 of 125 patients (5%) and consisted of either slippage of the rods or displacement of the set screws from the S2AI tulip head, with resultant kyphotic fracture. All failures occurred within 6 weeks postoperatively. Revision with a minimum of 4 rods connecting to 4 pelvic fixation points was successful. Two of 3 (66%) patients whose revision had less fixation sustained a second failure. Patients who experienced failure were younger (56.5 years vs 65 years, p = 0.03). The magnitude of surgical correction was higher in the failure cohort (number of levels fused, change in lumbar lordosis, change in T1-pelvic angle, and change in coronal C7 vertical axis, each p < 0.05). In the multivariate analysis, younger patient age and change in lumbar lordosis were independently associated with increased failure risk (p < 0.05 for each). There was a trend toward the presence of a transitional S1-2 disc being a risk factor (OR 8.8, 95% CI 0.93-82.6). Failure incidence was the same across implant manufacturers (p = 0.3). CONCLUSIONS: All failures involved large-magnitude correction and resulted from stresses that exceeded the failure loads of the set plugs in the S2AI tulip, with resultant rod displacement and kyphotic fractures. Patients with large corrections may benefit from 4 total S2AI screws at the time of the index surgery, particularly if a transitional segment is present. Salvage with a minimum of 4 rods and 4 pelvic fixation points can be successful.

A radiomics-based model for predicting local control of resected brain metastases receiving adjuvant SRS.

PURPOSE: Adjuvant radiosurgery to the cavities of surgically resected brain metastases provides excellent local tumor control while reducing the risk of deleterious cognitive decline associated with whole brain radiotherapy. A subset of these patients, however, will develop disease recurrence following radiosurgery. In this study, we sought to assess the predictive capability of radiomic-based models, as compared with standard clinical features, in predicting local tumor control. METHODS: We performed a retrospective chart review of patients treated with adjuvant radiosurgery for resected brain metastases at the "Institution" from 2009 to 2019. Shape, intensity and texture based radiomics features of the cavities were extracted from the pre-radiosurgery treatment planning MRI scans and trained using a gradient boosting technique with K-fold cross validation. RESULTS: In total, 71 cavities from 67 treated patients were included for analysis. The 6 and 12 month local control estimates were 86% and 76%, respectively. The 6 and 12 month overall survival was 78% and 55%, respectively. Thirty-six patients developed intracranial failures outside of the surgical cavity. The predictive model for local control trained on imaging features from the whole cavity achieved an area-under-the-curve (AUC) of 0.73 on the validation set versus an AUC of 0.40 for the clinical features. CONCLUSIONS: Here we report a single institutional experience using radiomic-based predictive modeling of local tumor control following adjuvant Gamma Knife radiosurgery for resected brain metastases. We found the radiomics features to provide more robust predictive models of local control rates versus clinical features alone. Such techniques could potentially prove useful in the clinical setting and warrant further investigation.

Improving Our Ability to Predict Resident Applicant Performance: Validity Evidence for a Situational Judgment Test.

Construct: We investigated whether a situational judgment test (SJT) designed to measure professionalism in physicians predicts residents' performance on (a) Accreditation Council for Graduate Medical Education (ACGME) competencies and (b) a multisource professionalism assessment (MPA). Background: There is a consensus regarding the importance of assessing professionalism and interpersonal and communication skills in medical students, residents, and practicing physicians. Nonetheless, these noncognitive competencies are not well measured during medical education selection processes. One promising method for measuring these noncognitive competencies is the SJT. In a typical SJT, respondents are presented with written or video-based scenarios and asked to make choices from a set of alternative courses of action. Interpersonally oriented SJTs are commonly used for selection to medical schools in the United Kingdom and Belgium and for postgraduate selection of trainees to medical practice in Belgium, Singapore, Canada, and Australia. However, despite international evidence suggesting that SJTs are useful predictors of in-training performance, end-of-training performance, supervisory ratings of performance, and clinical skills licensing objective structured clinical examinations, the use of interpersonally oriented SJTs in residency settings in the United States has been infrequently investigated. The purpose of this study was to investigate whether residents' performance on an SJT designed to measure professionalism-related competencies-conscientiousness, integrity, accountability, aspiring to excellence, teamwork, stress tolerance, and patient-centered care-predicts both their current and future performance as residents on two important but conceptually distinct criteria: ACGME competencies and the MPA. Approach: We developed an SJT to measure seven dimensions of professionalism. During calendar year 2017, 21 residency programs from 2 institutions administered the SJT. We conducted analyses to determine the validity of SJT and USMLE scores in predicting milestone performance in ACGME core competency domains and the MPA in June 2017 and 3 months later in September 2017 for the MPA and 1 year later, in June 2018, for ACGME domains. Results: At both periods, the SJT score predicted overall ACGME milestone performance (r = .13 and .17, respectively; p < .05) and MPA performance (r = .19 and .21, respectively; p < .05). In addition, the SJT predicted ACGME patient care, systems-based practice, practice-based learning and improvement, interpersonal and communication skills, and professionalism competencies (r = .16, .15, .15, .17, and .16, respectively; p < .05) 1 year later. The SJT score contributed incremental validity over USMLE scores in predicting overall ACGME milestone performance (ΔR = .07) 1 year later and MPA performance (ΔR = .05) 3 months later. Conclusions: SJTs show promise as a method for assessing noncognitive attributes in residency program applicants. The SJT's incremental validity to the USMLE series in this study underscores the importance of moving beyond these standardized tests to a more holistic review of candidates that includes both cognitive and noncognitive measures.

Cartilage-binding antibodies induce pain through immune complex-mediated activation of neurons.

Rheumatoid arthritis-associated joint pain is frequently observed independent of disease activity, suggesting unidentified pain mechanisms. We demonstrate that antibodies binding to cartilage, specific for collagen type II (CII) or cartilage oligomeric matrix protein (COMP), elicit mechanical hypersensitivity in mice, uncoupled from visual, histological and molecular indications of inflammation. Cartilage antibody-induced pain-like behavior does not depend on complement activation or joint inflammation, but instead on tissue antigen recognition and local immune complex (IC) formation. smFISH and IHC suggest that neuronal Fcgr1 and Fcgr2b mRNA are transported to peripheral ends of primary afferents. CII-ICs directly activate cultured WT but not FcRγ chain-deficient DRG neurons. In line with this observation, CII-IC does not induce mechanical hypersensitivity in FcRγ chain-deficient mice. Furthermore, injection of CII antibodies does not generate pain-like behavior in FcRγ chain-deficient mice or mice lacking activating FcγRs in neurons. In summary, this study defines functional coupling between autoantibodies and pain transmission that may facilitate the development of new disease-relevant pain therapeutics.

Controlled Pedicle Subtraction Osteotomy Site Closure Using Flexible Hinge-Powered Operating Table.

BACKGROUND AND IMPORTANCE: Pedicle subtraction osteotomy (PSO) is a 3-column osteotomy used to correct rigid, large magnitude sagittal spinal deformity. PSO is an inherently destabilizing procedure intraoperatively, with high risk of neurological deficits from vertebral body subluxation or translation during osteotomy closure. Traditionally, PSO closure has been performed utilizing compression or cantilevering forces across adjacent level instrumentation. Such forces can loosen the instrumentation or cause abrupt subluxation or translation due to the magnitude of force required for PSO closure, resulting in neurological injury. Here, we report using a flexible hinge-powered operating table for controlled closure of PSO in 1º increments via remote-control power of the table, without compression or cantilevering force required across implants. CLINICAL PRESENTATION: The patient is a 68-yr-old man with a history of prior L2-S1 anterior-posterior fusion, healed sacral fracture, and left sacroiliac joint fusion presenting to our institution with severe back pain while standing. X-rays demonstrated significant sagittal malalignment with pelvic incidence (PI) of 79º and lumbar lordosis (LL) of 37º, while computed tomography scan confirms complete bone healing around prior interbody fusion sites, resulting in rigid sagittal deformity. Due to rigid PI-LL mismatch of 42º, we planned for L2-pelvis revision fusion with L4 PSO. CONCLUSION: Here we demonstrate the utility of a flexible hinge-powered operating table for closure of PSO site. This technique eliminates force application to adjacent implants, minimizing vertebral body subluxation, or translation. We believe this allows for safer, more controllable osteotomy closure that minimizes risk of neurological injury.

Treatment Combining CD200 Immune Checkpoint Inhibitor and Tumor-Lysate Vaccination after Surgery for Pet Dogs with High-Grade Glioma.

Recent advances in immunotherapy have included inhibition of immune checkpoint proteins in the tumor microenvironment and tumor lysate-based vaccination strategies. We combined these approaches in pet dogs with high-grade glioma. Administration of a synthetic peptide targeting the immune checkpoint protein, CD200, enhanced the capacity of antigen-presenting cells to prime T-cells to mediate an anti-glioma response. We found that in canine spontaneous gliomas, local injection of a canine-specific, CD200-directed peptide before subcutaneous delivery of an autologous tumor lysate vaccine prolonged survival relative to a historical control treated with autologous tumor lysate alone (median survivals of 12.7 months and 6.36 months, respectively). Antigen-presenting cells and T-lymphocytes primed with this peptide suppressed their expression of the inhibitory CD200 receptor, thereby enhancing their ability to initiate immune reactions in a glioblastoma microenvironment replete with the immunosuppressive CD200 protein. These results support consideration of a CD200 ligand as a novel glioblastoma immunotherapeutic agent.

A Comparison of the Existing Wellness Programs in Neurosurgery and Institution Champion's Perspectives.

Once the accepted norm during Harvey Cushing's time, the mantra of work to the exclusion of family and lifestyle is now recognized as deleterious to overall well-being. A number of neurosurgical residency training programs have implemented wellness programs to enhance the physical, mental, and emotional well-being of trainees and faculty. This manuscript highlights existing organized wellness education within neurosurgery residency programs in order to describe the motivations behind development, structure, and potential implementation strategies, cost of implementation, and identify successes and barriers in the integration process. This manuscript is designed to serve as a "how-to" guide for other programs who may identify a need in their own trainees and begins the discussion of how to develop wellness, leadership, grit, and resiliency within our future generation of neurosurgeons.

Development of New Analgesics: An Answer to Opioid Epidemic.

Management of pain is a fundamental imperative in medicine. Current analgesics suffer from limitations related to efficacy and adverse events of which abuse potential has assumed an important role. Here we highlight the factors that drive the development of novel analgesics and the advances made in the field.

Naturally Occurring Canine Glioma as a Model for Novel Therapeutics.

BACKGROUND: Current animal models of glioma are limited to small animal models, which are less predictive of treatment of human disease. Canines often develop gliomas de novo, but the natural history of the disease is not well described. OBJECTIVE: We provide data for naturally occurring canine gliomas; evaluating medical and surgical therapies. METHODS: We reviewed medical records of pet dogs with a presumptive diagnosis of glioma from MRI imaging that underwent surgery as part of the Canine Brain Tumor Clinical Trials Program. Breed, age, sex, median progression-free, and overall survival times and cause of death were recorded for multivariate analysis. RESULTS: Ninety five dogs (56 male; mean age = 8.3 years) were included, but nine were excluded as final pathology was non-neoplastic. Gross total resection was reported in 81 cases based on postoperative MRI. Seventy had high-grade tumors (grade III or IV). Eighty three dogs presented with seizures, being the most common presenting clinical sign. Median survival after surgery was 723 days (95% CI 343-1103) for grade II tumors, 301 days (197-404) for grade III and 200 days (126-274) for grade IV (p = .009 Kaplan-Meier survival analysis; Log Rank test). Age (cox regression, p = .14) or sex (Kaplan-Meier test, p = .22) did not predict survival. CONCLUSIONS: This study establishes normative data for a model exploiting dogs with naturally occurring glioma, which can be used to test novel therapies prior to translation to human trials. Further work will focus on the effects of different therapies, including chemotherapy, radiation therapy, and immunotherapy.

Near complete response to Pembrolizumab in microsatellite-stable metastatic sebaceous carcinoma.

BACKGROUND: Sebaceous carcinoma is an aggressive adnexal skin tumor with a predilection for the eyelids and sebaceous glands of the head and neck. CASE PRESENTATION: A 73 year-old man presented with confusion and was found to have widely disseminated sebaceous carcinoma with metastases to brain, lungs, liver, bowel, lymph nodes, and bone. Following initial treatment of the brain metastases with surgery he received post-operative radiosurgery. He then began systemic immunotherapy with pembrolizumab. After 6 months, he developed a near complete response to therapy by irRECIST and RECIST v.1.1. The response was associated with circulating CD8+ T cells with central memory (CM) and effector memory (EM) phenotype and mature CD16 + CD57+ NK cells. During treatment the patient developed adrenal insufficiency requiring high-dose systemic corticosteroids and later adrenal replacement therapy. After 12-months of follow-up he showed imaging evidence of progression in liver, mediastinum, and abdominal lymph nodes. Given persistent, strong PD-L1 expression he resumed pembrolizumab therapy and showed radiographic evidence of an ongoing response to therapy. CONCLUSIONS: This is the first report describing objective clinical and radiographic responses following immunotherapy for widely metastatic sebaceous carcinoma. The dramatic therapeutic response to pembrolizumab was associated with peripheral blood circulating memory T cells and mature Natural Killer cells after 6 months (24 weeks) of therapy. This report supports prospective clinical trials of anti-PD1 checkpoint blockade for metastatic sebaceous carcinoma.

Electronic Residency Application Service Application Characteristics Associated with Successful Residency Matching in Neurosurgery in 2009-2016.

BACKGROUND: Resident applicants in neurosurgery often wonder what factors impact their chances of successfully matching. Using data published by the National Residency Match Program for 2009-2016, we examined which components of the Electronic Residency Application Service application correlated with successful residency matching. METHODS: Data were collected from the National Residency Match Program publication Charting Outcomes in the Match from all years it was available for neurosurgery (2009, 2011, 2014, 2016). Individual factors reported (number of contiguous ranks, research projects, publications and presentations, work experiences, volunteer experiences, United States Medical Licensing Examination Step 1 and 2 score deciles, categorical data about Alpha Omega Alpha status, Ph.D. degree, other degree, and strength of medical school National Institutes of Health funding) were aggregated for all 3 years. Categorical data were available only for U.S. seniors. Spearman correlation and χ2 were used for ranked data and categorical data, respectively. Separate analyses were run for U.S. seniors and independent applicants. RESULTS: For U.S. seniors applying to neurosurgery, number of contiguous ranks, United States Medical Licensing Examination Step 1 and 2 scores, research projects, Alpha Omega Alpha status, and medical school top 40 National Institutes of Health funding were significantly associated with successful matching of applicants. Number of volunteer experiences was nearly statistically significant. For independent applicants, only United States Medical Licensing Examination Step 1 and 2 scores and number of research projects were statistically significant. CONCLUSIONS: This is the first study to analyze National Residency Match Program data for predictors of success in neurosurgical matching. Students applying to neurosurgery residency and their mentors should be aware of which baseline objective factors are associated with match success.

Autoantibodies Hurt: Transfer of Patient-Derived CASPR2 Antibodies Induces Neuropathic Pain in Mice.

In this issue of Neuron, Dawes et al. (2018) show that CASPR2 antibodies (Abs) isolated from patients bind specifically to primary afferent cell bodies and induce neuropathic pain in mice. Consequent decreased expression of Kv1 channels and their aberrant localization along myelinated axons explain the observed hyperexcitability and pain.

Incidence of and risk factors for major complications or death in dogs undergoing cytoreductive surgery for treatment of suspected primary intracranial masses.

OBJECTIVE To determine incidence of and risk factors for major complications occurring in dogs within 30 days after cytoreductive surgery performed by a single pair of surgeons for treatment of suspected primary intracranial masses. DESIGN Retrospective cohort study. ANIMALS 160 client-owned dogs that underwent cytoreductive surgery for treatment of suspected primary intracranial masses between January 2009 and December 2015 at a veterinary teaching hospital. PROCEDURES Medical records were retrospectively reviewed for complications occurring within 30 days after surgery. Data (eg, signalment, clinical signs, previous treatments, preoperative neurologic examination findings, neuroanatomical location, time from onset of clinical signs to surgery, surgical approach, and histopathologic diagnosis) were analyzed for associations with death and with development of major complications other than death. RESULTS 21 (13.1%) dogs died (11 during hospitalization and 10 after discharge) and 30 (18.8%) developed major complications other than death during the first 30 days after surgery. Dogs with abnormal preoperative neurologic examination findings were more likely to develop complications or die. Dogs undergoing a suboccipital approach were more likely to die. The most common postoperative complications other than death were seizures (n = 18 [11.3%]), worsening of neurologic status (6 [3.8%]), and aspiration pneumonia (6 [3.8%]). CONCLUSIONS AND CLINICAL RELEVANCE Results of the present study provided valuable information on predisposing factors, odds of major complications or death, and incidences of major complications or death in dogs during the first 30 days after undergoing cytoreductive surgery for treatment of suspected primary intracranial masses. Careful case selection may help improve outcomes and minimize complications.