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The LACE+ index (Length of stay, Acuity of admission, Charlson Comorbidity Index score, and Emergency department [ED] visits in the past 6 months) is a tool used to predict 30-day readmissions. We sought to examine this predictive tool in patients undergoing brain tumor surgery.Admissions and readmissions for patients undergoing craniotomy for supratentorial neoplasm at a single multihospital academic medical center were analyzed. All brain tumor cases for which the patient was alive at 30 days after surgery were included (n = 352). Simple logistic regression analyses were used to assess the ability of the LACE+ index and subsequent single variables to accurately predict the outcome measures of 30-day readmission, reoperation, and ED visit. Analysis of the model's or variable's discrimination was determined by the receiver operating characteristic curve as represented by the C-statistic.The sample included admissions for craniotomy for supratentorial neoplasm (n = 352). Assessment of the LACE+ index demonstrates a 1.02× increased odds of 30-day readmission for every 1-unit increase in LACE+ score (P = 0.031, CI = 1.00-1.03). Despite this, analysis of the receiver operating characteristic curve indicates that LACE+ index has poor specificity in predicting 30-day readmission (C-statistic = 0.58). A 1-unit increase in LACE+ score also predicts a 0.98× reduction in odds of home discharge (P0.001, CI = 0.97-0.99, C-statistic = 0.70). But LACE+ index does not predict 30-day reoperation (P = 0.945) or 30-day ED visits (P = 0.218).The results of this study demonstrate that the LACE+ index is not yet suitable as a prediction model for 30-day readmission in a brain tumor population.

BACKGROUND Limited data exist on the safety of overlapping surgery, a practice that has recently received widespread attention. OBJECTIVE To examine the association of overlapping neurosurgery with patient outcomes. METHODS A total of 3038 routinely scheduled, elective neurosurgical procedures were retrospectively reviewed at a single, multihospital academic medical center. Procedures were categorized into any overlap or no overlap and further subcategorized into beginning overlap (first 50% of procedure only), end overlap (last 50% of procedure only), and middle overlap (overlap at the midpoint). RESULTS A total of 1030 (33.9%) procedures had any overlap, whereas 278 (9.2%) had beginning overlap, 190 (6.3%) had end overlap, and 476 (15.7%) had middle overlap. Compared with no overlap patients, patients with any overlap had lower American Society of Anesthesiologists scores (P = .0018), less prior surgery (P

Intervertebral disc degeneration is strongly associated with chronic low back pain, a leading cause of disability worldwide. Current back pain treatment approaches (both surgical and conservative) are limited to addressing symptoms, not necessarily the root cause. Not surprisingly therefore, long‐term efficacy of most approaches is poor. Cell‐based disc regeneration strategies have shown promise in preclinical studies, and represent a relatively low‐risk, low‐cost, and durable therapeutic approach suitable for a potentially large patient population, thus making them attractive from both clinical and commercial standpoints. Despite such promise, no such therapies have been broadly adopted clinically. In this perspective we highlight primary obstacles and provide recommendations to help accelerate successful clinical translation of cell‐based disc regeneration therapies. The key areas addressed include: (a) Optimizing cell sources and delivery techniques; (b) Minimizing potential risks to patients; (c) Selecting physiologically and clinically relevant efficacy metrics; (d) Maximizing commercial potential; and (e) Recognizing the importance of multidisciplinary collaborations and engaging with clinicians from inception through to clinical trials.

Chordomas are rare, locally aggressive neoplasms that develop from remnants of the notochord. The typical approach to chordomas of the clivus and axial cervical spine often limits successful en bloc resection. In this case report, authors describe the first-documented transoral approach using both transoral robotic surgery (TORS) for exposure and the Sonopet bone scalpel under navigational guidance to achieve en bloc resection of a cervical chordoma. This 27-year-old man had no significant past medical history (Charlson Comorbidity Index 0). During a trauma workup following a motor vehicle collision, a CT of the patient’s cervical spine demonstrated an incidental 2.2-cm lesion situated along the posterior aspect of the C2 vertebral body. Postoperative imaging showed successful en bloc resection with adequate placement of hardware, and the pathology report demonstrated negative resection margins. The patient tolerated the procedure well, and because of the successful en bloc resection, radiation has been deferred. At 7 months postoperatively, the patient returned to work in New York City. Contrasted MRI at 15 months postoperatively showed the patient to be disease free. This approach offers a promising way forward in the treatment of these complex tumors.

Background Bundled care payment models are becoming more prevalent in neurosurgery. Such systems place the cost of postsurgical facilities in the hands of the discharging health system. Opportunity exists to leverage prediction tools for discharge disposition by identifying patients who will not benefit from prolonged hospitalization and facilitating discharge to post-acute care facilities. Objective To validate the use of the Risk Assessment and Predictive Tool (RAPT) along with other clinical variables to predict discharge disposition in a cervical spine surgery population. Methods Patients undergoing cervical spine surgery at our institution from June 2016 to February 2017 and over 50 yr old had demographic, surgical, and RAPT variables collected. Multivariable regression analyzed each variable's ability to predict discharge disposition. Backward selection was used to create a binomial model to predict discharge disposition. Results A total of 263 patients were included in the study. Lower RAPT score, RAPT walk subcomponent, older age, and a posterior approach predicted discharge to a post-acute care facility compared to home. Lower RAPT also predicted an increased risk of readmission. RAPT score combined with age increased the predictive capability of discharge disposition to home vs skilled nursing facility or acute rehabilitation compared to RAPT alone (P Conclusion RAPT score combined with age is a useful tool in the cervical spine surgery population to predict postdischarge needs. This tool may be used to start early discharge planning in patients who are predicted to require post-acute care facilities. Such strategies may reduce postoperative utilization of inpatient resources.

OBJECTIVE Our objective was to determine the impact of total preincision infusion time on surgical site infections (SSIs) and establish an optimal time threshold for subsequent prospective study. BACKGROUND SSIs remain a major cause of morbidity. Although regulated, the total time of infusion of preincision antibiotics varies widely. Impact of infusion time on SSI risk is poorly understood. METHODS All consecutive patients (n = 46,791) undergoing inpatient surgical intervention were retrospectively enrolled (2014-2015) and monitored for 1 year. Primary outcomes: the presence of SSI infection as predicted by reduced preoperative antibiotic infusion time. SECONDARY OUTCOMES preintervention compliance, the impact of a quality improvement algorithm to optimize infusion time compliance. Multivariate logistic regression of the retrospective cohort demonstrated predictors of infection. Receiver-operating characteristic analysis demonstrated the timing threshold predictive of infection. Cost impact of avoidable infections was analyzed. RESULTS Only 36.1% of patients received preincision infusion of vancomycin in compliance with national and institutional standards (60-120 min). Cephalosporin infusion times were 53 times more likely to be compliant [odds ratio (OR) 53.33, P < 0.001]. Vancomycin infusion times that were not compliant with national standards (less than standard 60-120 min) did not predict infection. However, significantly noncompliant, reduced preincision infusion time, significantly predicted SSI (

OBJECTIVEEnhanced recovery after surgery (ERAS) protocols address pre-, peri-, and postoperative factors of a patient’s surgical journey. The authors sought to assess the effects of a novel ERAS protocol on clinical outcomes for patients undergoing elective spine or peripheral nerve surgery.METHODSThe authors conducted a prospective cohort analysis comparing clinical outcomes of patients undergoing elective spine or peripheral nerve surgery after implementation of the ERAS protocol compared to a historical control cohort in a tertiary care academic medical center. Patients in the historical cohort (September–December 2016) underwent traditional surgical care. Patients in the intervention group (April–June 2017) were enrolled in a unique ERAS protocol created by the Department of Neurosurgery at the University of Pennsylvania. Primary objectives were as follows: opioid and nonopioid pain medication consumption, need for opioid use at 1 month postoperatively, and patient-reported pain scores. Secondary objectives were as follows: mobilization and ambulation status, Foley catheter use, need for straight catheterization, length of stay, need for ICU admission, discharge status, and readmission within 30 days.RESULTSA total of 201 patients underwent surgical care via an ERAS protocol and were compared to a total of 74 patients undergoing traditional perioperative care (control group). The 2 groups were similar in baseline demographics. Intravenous opioid medications postoperatively via patient-controlled analgesia was nearly eliminated in the ERAS group (0.5% vs 54.1%, p < 0.001). This change was not associated with an increase in the average or daily pain scores in the ERAS group. At 1 month following surgery, a smaller proportion of patients in the ERAS group were using opioids (38.8% vs 52.7%, p = 0.041). The ERAS group demonstrated greater mobilization on postoperative day 0 (53.4% vs 17.1%, p < 0.001) and postoperative day 1 (84.1% vs 45.7%, p < 0.001) compared to the control group. Postoperative Foley use was decreased in the ERAS group (20.4% vs 47.3%, p < 0.001) without an increase in the rate of straight catheterization (8.1% vs 11.9%, p = 0.51).CONCLUSIONSImplementation of this novel ERAS pathway safely reduces patients’ postoperative opioid requirements during hospitalization and 1 month postoperatively. ERAS results in improved postoperative mobilization and ambulation.

OBJECTIVEHealthcare costs continue to escalate. Approaches to care that have comparable outcomes and complications are increasingly assessed for quality improvement and, when possible, cost containment. Efforts to identify components of care to reduce length of stay (LOS) have been ongoing. Spinal anesthesia (SA), for select lumbar spine procedures, has garnered interest as an alternative to general anesthesia (GA) that might reduce cost and in-hospital LOS and accelerate recovery. While clinical outcomes with SA or GA have been studied extensively, few authors have looked at the cost-analysis in relation to clinical outcomes. The authors' objectives were to compare the clinical perioperative outcomes of patients who received SA and GA, as well as the direct costs associated with each modality of care, and to determine which, in a retrospective analysis, can serve as a dominant procedural approach.METHODSThe authors retrospectively analyzed a homogeneous surgical population of 550 patients who underwent hemilaminotomy for disc herniation and who received either SA (n = 91) or GA (n = 459). All clinical and billing data were obtained via each patient's chart and the hospital's billing database, respectively. Additionally, the authors prospectively assessed patient-reported outcome measures for a subgroup of consecutively treated patients (n = 75) and compared quality-adjusted life year (QALY) gains between the two cohorts. Furthermore, the authors performed a propensity score-matching analysis to compare the two cohorts (n = 180).RESULTSDirect hospital costs for patients receiving SA were 40% higher, in the hundreds of dollars, than for patients who received GA (p0.0001). Furthermore, there was a significant difference with regard to LOS (p0.0001), where patients receiving SA had a considerably longer hospital LOS (27.6% increase in hours). Patients undergoing SA had more comorbidities (p = 0.0053), specifically diabetes and hypertension. However, metrics of complications, including readmission (p = 0.3038) and emergency department (ED) visits at 30 days (p = 1.0), were no different. Furthermore, in a small pilot group, QALY gains were statistically no different (n = 75, p = 0.6708). Propensity score-matching analysis demonstrated similar results as the univariate analysis: there was no difference between the cohorts regarding 30-day readmission (p = 1.0000); ED within 30 days could not be analyzed as there were no patients in the SA group; and total direct costs and LOS were significantly different between the two cohorts (p0.0001 and p = 0.0126, respectively).CONCLUSIONSBoth SA and GA exhibit the qualities of a good anesthetic, and the utilization of these modalities for lumbar spine surgery is safe and effective. However, this work suggests that SA is associated with increased LOS and higher direct costs, although these differences may not be clinically or fiscally meaningful.

The impact of underlying liver disease on surgical outcomes has been recognized in a wide variety of surgical disciplines. However, less empiric data are available about the importance of liver disease in spinal surgery.To measure the independent impact of underlying liver disease on 30-day outcomes following surgery for the degenerative cervical spine.Retrospective comparative study.A cohort of 21,207 patients undergoing elective surgery for degenerative disease of the cervical spine from the American College of Surgeons National Surgical Quality Improvement Program.Outcome measures included mortality, hospital length of stay, and postoperative complications within 30 days of surgery.The NSQIP dataset was queried for patients undergoing surgery for degenerative disease of the cervical spine from 2006 to 2015. Assessment of underlying liver disease was based on aspartate aminotransferase-to-platelet ratio index and Model of End-Stage Liver Disease-Sodium scores, computed from preoperative laboratory data. The effect of liver disease on outcomes was assessed by bivariate and multivariate analyses, in comparison with 16 other preoperative and operative factors.Liver disease could be assessed in 21,207 patients based on preoperative laboratory values. Mild liver disease was identified in 2.2% of patients, and advanced liver disease was identified in 1.6% of patients. The 30-day mortality rates were 1.7% and 5.1% in mild and advanced liver diseases, respectively, compared with 0.6% in patients with healthy livers. The 30-day complication rates were 11.8% and 31.5% in these patients, respectively, compared with 8.8% in patients with healthy livers. In multivariate analysis, the presence of any liver disease (mild or advanced) was independently associated with an increased risk of mortality (OR=2.00, 95% CI=1.12-3.55, p=.019), morbidity (OR=1.35, 95% CI=1.07-1.70, p=.012), and length of hospital stay longer than 7 days (OR=1.73, 95% CI=1.40-2.13, p.001), when compared with 18 other preoperative and operative factors. Liver disease was also independently associated with perioperative respiratory failure (OR=1.80, 95% CI=1.21-2.68, p=.004), bleeding requiring transfusion (OR=1.43, 95% CI=1.01-2.02, p=.044), wound disruption (OR=2.82, 95% CI=1.04-7.66, p=.042), and unplanned reoperation (OR=1.49, 95% CI=1.05-2.11, p=.025).Liver disease independently predicts poor perioperative outcome following surgery for degenerative disease of the cervical spine. Based on these findings, careful consideration of a patient's underlying liver function before surgery may prove valuable in surgical decision-making, preoperative patient counseling, and postoperative patient care.

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient β-glucuronidase activity, which leads to the accumulation of incompletely degraded glycosaminoglycans (GAGs). MPS VII patients present with severe skeletal abnormalities, which are particularly prevalent in the spine. Incomplete cartilage-to-bone conversion in MPS VII vertebrae during postnatal development is associated with progressive spinal deformity and spinal cord compression. The objectives of this study were to determine the earliest postnatal developmental stage at which vertebral bone disease manifests in MPS VII and to identify the underlying cellular basis of impaired cartilage-to-bone conversion, using the naturally-occurring canine model. Control and MPS VII dogs were euthanized at 9 and 14 days-of-age, and vertebral secondary ossification centers analyzed using micro-computed tomography, histology, qPCR, and protein immunoblotting. Imaging studies and mRNA analysis of bone formation markers established that secondary ossification commences between 9 and 14 days in control animals, but not in MPS VII animals. mRNA analysis of differentiation markers revealed that MPS VII epiphyseal chondrocytes are unable to successfully transition from proliferation to hypertrophy during this critical developmental window. Immunoblotting demonstrated abnormal persistence of Sox9 protein in MPS VII cells between 9 and 14 days-of-age, and biochemical assays revealed abnormally high intra and extracellular GAG content in MPS VII epiphyseal cartilage at as early as 9 days-of-age. In contrast, assessment of vertebral growth plates and primary ossification centers revealed no significant abnormalities at either age. The results of this study establish that failed vertebral bone formation in MPS VII can be traced to the failure of epiphyseal chondrocytes to undergo hypertrophic differentiation at the appropriate developmental stage, and suggest that aberrant processing of Sox9 protein may contribute to this cellular dysfunction. These results also highlight the importance of early diagnosis and therapeutic intervention to prevent the progression of debilitating skeletal disease in MPS patients.

Study Design Prospective observational study. Objective To determine whether preference-based health utility scores for common spinal radiculopathies vary by specific spinal level. Methods We employed a standard gamble study using the general public to calculate individual preference-based quality of life for four common radiculopathies: C6, C7, L5, and S1. We compared utility scores obtained for each level of radiculopathy with analysis of variance and t test. Multivariable regression was used to test the effects of the covariates age, sex, and years of education. We also reviewed the literature for publications reporting EuroQol-5 Dimensions (EQ-5D) scores for patients with radiculopathy. Results Two hundred participants were included in the study. Average utility for the four spinal levels fell within a narrow range (0.748 to 0.796). There were no statistically significant differences between lumbar and cervical radiculopathies, nor were there significant differences among the different spinal levels ( F = 0.0850, p = 0.086). Age and sex had no significant effect on utility scores. There was a significant correlation between years of education and utility values for S1 radiculopathy ( p = 0.037). On review of the literature, no study separated utility values by specific spinal level. EQ-5D utilities for both cervical and lumbar radiculopathy were considerably lower than the results of our study. Conclusions Utility values associated with the most common levels of cervical and lumbar radiculopathy do not significantly differ from each other, validating the current practice of grouping utility by spinal segment rather than by specific root levels. The discrepancy in average utility values between our study and the EQ-5D highlights the need to be mindful of the underlying instruments used when assessing outcomes studies from different sources.

Degeneration of the intervertebral discs is strongly implicated as a cause of low back pain. Since current treatments for discogenic low back pain show poor long-term efficacy, a number of new biological strategies are being pursued. For such therapies to succeed, it is critical that they be validated in conditions that mimic the unique biochemical microenvironment of the nucleus pulposus (NP), which include low oxygen tension. Therefore, the objective of this study was to investigate the effects of oxygen tension on NP cell functional extracellular matrix elaboration in 3D culture. Bovine NP cells were encapsulated in agarose constructs and cultured for 14 or 42 days in either 20% or 2% oxygen in defined media containing transforming growth factor beta-3. At each time point, extracellular matrix composition, biomechanics, and mRNA expression of key phenotypic markers were evaluated. Results showed that while bulk mechanics and composition were largely independent of oxygen level, low oxygen promoted improved restoration of the NP phenotype, higher mRNA expression of extracellular matrix and NP specific markers, and more uniform matrix elaboration. These findings indicate that culture under physiological oxygen levels is an important consideration for successful development of cell and growth factor-based regenerative strategies for the disc.

Low back pain due to disc degeneration is a major cause of morbidity and health care expenditures worldwide. While stem cell-based therapies hold promise for disc regeneration, there is an urgent need to develop improved in vivo animal models to further develop and validate these potential treatments. The objectives of this study were to characterize a percutaneous needle injury model of intervertebral disc degeneration in the mouse caudal spine, and compare two non-invasive quantitative imaging techniques, microcomputed tomography and magnetic resonance imaging (MRI), as effective measures of disc degeneration in this model. Percutaneous needle injury of mouse caudal discs was undertaken using different needle sizes and injury types (unilateral or bilateral annulus fibrosus (AF) puncture). Mice were euthanized 4 weeks post-injury, and MRI and microcomputed tomography were used to determine T2 relaxation time of the NP and disc height index, respectively. Disc condition was then further assessed using semi-quantitative histological grading. Bilateral AF puncture with either 27 or 29G needles resulted in significantly lower T2 relaxation times compared to uninjured controls, while disc height index was not significantly affected by any injury type. There was a strong, inverse linear relationship between histological grade and NP T2 relaxation time. In this study, we demonstrated that quantitative MRI can detect disc degeneration in the mouse caudal spine 4 weeks following percutaneous needle injury, and may therefore serve as a surrogate for histology in longitudinal studies of both disc degeneration and cell-based therapies for disc regeneration using this model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2771-2779, 2018.

Objective Despite surgical, technological, medical, and anesthetic improvements, patient outcomes following elective neurosurgical procedures can be associated with high morbidity. Enhanced recovery after surgery (ERAS) protocols are multimodal care pathways designed to optimize patient outcomes by addressing pre-, peri-, and post-operative factors. Despite significant data suggesting improved patient outcomes with the adoption of these pathways, development and implementation has been limited in the neurosurgical population. Methods/Results This study protocol was designed to establish the feasibility of a randomized controlled trial to assess the efficacy of implementation of an ERAS protocol on the improvement of clinical and patient reported outcomes and patient satisfaction scores in an elective inpatient spine surgery population. Neurosurgical patients undergoing spinal surgery will be recruited and randomly allocated to one of two treatment arms: ERAS protocol (experimental group) or hospital standard (control group). The experimental group will undergo interventions at the pre-, peri-, and post-operative time points, which are exclusive to this group as compared to the hospital standard group. Conclusions The present proposal aims to provide supporting data for the application of these specific ERAS components in the spine surgery population and provide rationale/justification of this type of care pathway. This study will help inform the design of a future multi-institutional, randomized controlled trial. Results of this study will guide further efforts to limit post-operative morbidity in patients undergoing elective spinal surgery and to highlight the impact of ERAS care pathways in improving patient reported outcomes and satisfaction.

Recapitulation of developmental signals represents a promising strategy for treating intervertebral disc degeneration. During development, embryonic notochord-derived cells (NDCs) are the direct progenitors of cells that populate the adult nucleus pulposus (NP) and are an important source of secreted signaling molecules. The objective of this study was to define global gene expression profiles of NDCs at key stages of embryonic disc formation. NDCs were isolated from Shh-cre;ROSA:YFP mice at embryonic day 12.5 and postnatal day 0, representing opposite ends of the notochord to NP transformation. Differences in global mRNA abundance across this developmental window were established using RNA-Seq. Protein expression of selected molecules was confirmed using immunohistochemistry. Principal component analysis revealed clustering of gene expression at each developmental stage with more than 5000 genes significantly differentially expressed between E12.5 and P0. There was significantly lower mRNA abundance of sonic hedgehog pathway elements at P0 vs E12.5, while abundance of elements of the transforming growth factor-beta and insulin-like growth factors pathways, and extracellular matrix components including collagen 6 and aggrecan, were significantly higher at P0. This study represents the first transcriptome-wide analysis of embryonic NDCs. Results suggest signaling and biosynthesis of NDCs change dramatically as a function of developmental stage.

Objective Traumatic injuries, degenerative/rheumatologic conditions, tumors, or infections of the upper cervical spine may in certain circumstances require surgical stabilization. C1 lateral mass screws (Harms technique) in combination with C2 instrumentation (pars, pedicle, translaminar screws) have become a mainstay of surgical treatment. The surgical anatomy of the C1 lateral mass can be challenging especially with the robust venous plexus that often causes significant bleeding with exposure of the C1–C2 articular complex. The purpose of this study was to examine whether the use of navigation reduced intraoperative blood loss during atlantoaxial fixation. Methods We reviewed our institutional experience with atlantoaxial instrumentation with and without navigation from 2007 to 2016. We limited our cases to those requiring C1–C2 stabilization in traumatic and degenerative cases and not as part of more extensive surgical stabilizations. We identified 45 consecutive patients and compared intraoperative blood loss, need for transfusion, and time of procedure with and without the use of navigation. Results There was a significant reduction in the amount of intraoperative blood loss in the navigated (n = 20) versus non-navigated cases (n = 25). In addition, although the navigated cases initially were longer, currently there is no significant difference in the length of the cases. Conclusions In our series, surgical navigation significantly reduced blood loss compared with non-navigated cases without increasing surgical time or risk of complication. Furthermore, navigation has the potential to reduce operative times due to a reduction in blood loss.

The objective of this study is to investigate the prevalence and disparity of chronic opioid usage in surgical patients and the potential risk factors associated with chronic opioid usage.Chronic opioid usage is common in surgical patients; however, the characteristics of opioid usage in surgical patients is unclear. In this study, we hypothesize that the prevalence of chronic opioid usage in surgical patients is high, and that significant disparities may exist among different surgical populations.Data of opioid usage in outpatients among different surgical services were extracted from the electronic medical record database. Patient demographics, clinical characteristics of sex, age, race, body mass index (BMI), specialty visited, duration of opioid use, and opioid type were collected. Chronic opioid users were defined as patients who had been recorded as taking opioids for at least 90 days determined by the first and last visit dates under opioid usage during the investigation.There were 79,123 patients included in this study. The average prevalence is 9.2%, ranging from 4.4% to 23.8% among various specialties. The prevalence in orthopedics (23.8%), neurosurgery (18.7%), and gastrointestinal surgery (14.4%) ranked in the top three subspecialties. Major factors influencing chronic opioid use include age, Ethnicitiy, Subspecialtiy, and multiple specialty visits. Approximately 75% of chronic users took opioids that belong to the category II Drug Enforcement Administration classification.Overall prevalence of chronic opioid usage in surgical patients is high with widespread disparity among different sex, age, ethnicity, BMI, and subspecialty groups. Information obtained from this study provides clues to reduce chronic opioid usage in surgical patients.

The International Subarachnoid Aneurysm Trial heralded a paradigm shift in the treatment of intracranial aneurysms. During this same time frame, neurosurgical training programs increased in size and scope. The present study examines the impact of trends in surgical clipping and the endovascular treatment of intracranial aneurysms, over one decade, and the neurosurgical resident complement on the resident teaching environment using the Nationwide Inpatient Sample (NIS).The NIS was used to estimate the number of aneurysms treated with either surgical clipping and endovascular methods from 2002 through 2011 at teaching institutions. Teaching opportunities per year per resident or chief resident were calculated as the ratio of the number of specified cases to the average number of neurosurgical trainees by year. Annualized trends were assessed.Over the study period, the percent change in odds of occurrence of a clipped ruptured aneurysm was -15.6% per year (P0.001) and of ruptured aneurysms undergoing endovascular treatment was 18.7% per year (P 0.001) within teaching institutions. This corresponded to a decline in teaching opportunities for clipped ruptured aneurysms for both residents and chief residents (P 0.001). In contrast, teaching opportunities for endovascular treatment of both ruptured and unruptured aneurysms increased dramatically over the study period.There has been a significant decrease in opportunity for operative exposure to craniotomy for ruptured aneurysm clipping over the past decade, whereas the volume of endovascular procedures for aneurysms has dramatically increased, highlighting the need for a shift in training strategy for those neurosurgeons graduating from residency desiring to subspecialize in neurovascular neurosurgery.

STUDY DESIGN Cost-effectiveness analysis with decision analysis and meta-analysis. OBJECTIVE To determine the relative cost-effectiveness of anterior cervical discectomy with fusion (with autograft, allograft, or spacers), anterior cervical discectomy without fusion (ACD), and cervical disc replacement (CDR) for the treatment of 1-level cervical disc disease. SUMMARY OF BACKGROUND DATA There is debate as to the optimal anterior surgical strategy to treat single-level cervical disc disease. Surgical strategies include 3 techniques of anterior cervical discectomy with fusion (autograft, allograft, or spacer-assisted fusion), ACD, and CDR. Several controlled trials have compared these treatments but have yielded mixed results. Decision analysis provides a structure for making a quantitative comparison of the costs and outcomes of each treatment. METHODS A literature search was performed and yielded 156 case series that fulfilled our search criteria describing nearly 17,000 cases. Data were abstracted from these publications and pooled meta-analytically to estimate the incidence of various outcomes, including index-level and adjacent-level reoperation. A decision analytic model calculated the expected costs in US dollars and outcomes in quality-adjusted life years for a typical adult patient with 1-level cervical radiculopathy subjected to each of the 5 approaches. RESULTS At 5 years postoperatively, patients who had undergone ACD alone had significantly (P < 0.001) more quality-adjusted life years (4.885 ± 0.041) than those receiving other treatments. Patients with ACD also exhibited highly significant (P < 0.001) differences in costs, incurring the lowest societal costs ($16,558 ± $539). Follow-up data were inadequate for comparison beyond 5 years. CONCLUSION The results of our decision analytic model indicate advantages for ACD, both in effectiveness and costs, over other strategies. Thus, ACD is a cost-effective alternative to anterior cervical discectomy with fusion and CDR in patients with single-level cervical disc disease. Definitive conclusions about degenerative changes after ACD and adjacent-level disease after CDR await longer follow-up. LEVEL OF EVIDENCE 4.

Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease characterized by deficient α-L-iduronidase activity, leading to the accumulation of poorly degraded glycosaminoglycans (GAGs). Children with MPS I exhibit high incidence of spine disease, including accelerated disc degeneration and vertebral dysplasia, which in turn lead to spinal cord compression and kypho-scoliosis. In this study we investigated the efficacy of neonatal enzyme replacement therapy (ERT), alone or in combination with oral simvastatin (ERT+SIM) for attenuating cervical spine disease progression in MPS I, using a canine model. Four groups were studied: normal controls; MPS I untreated; MPS I ERT treated; and MPS I ERT+SIM treated. Animals were euthanized at one year-of-age. Intervertebral disc condition and spinal cord compression were evaluated from MRIs and plain radiographs, vertebral bone condition and odontoid hypoplasia were evaluated using microcomputed tomography, and epiphyseal cartilage to bone conversion was evaluated histologically. Untreated MPS I animals exhibited more advanced disc degeneration and more severe spinal cord compression than normal animals. Both treatment groups resulted in partial preservation of disc condition and cord compression, with ERT+SIM not significantly better than ERT alone. Untreated MPS I animals had significantly lower vertebral trabecular bone volume and mineral density, while ERT treatment resulted in partial preservation of these properties. ERT+SIM treatment demonstrated similar, but not greater, efficacy. Both treatment groups partially normalized endochondral ossification in the vertebral epiphyses (as indicated by absence of persistent growth plate cartilage), and odontoid process size and morphology. These results indicate that ERT begun from a very early age attenuates the severity of cervical spine disease in MPS I, particularly for the vertebral bone and odontoid process, and that additional treatment with simvastatin does not provide a significant additional benefit over ERT alone.

Background Traditionally, lumbar discectomy has involved overnight hospital admission. Recent literature supports the shift to same-day lumbar discectomy because of improved outcomes and better patient satisfaction scores. A successful protocol for outpatient lumbar discectomies was proposed and implemented at a single institution. The aim of this study is to perform a quantitative and qualitative analysis of this institutional model. Methods Retrospective clinical data were collected for patients who underwent a lumbar discectomy during the period 2008–2012. Admission and readmission rates, emergency department (ED) visit rates, surgical complications, and differences between neurosurgeons specializing in spinal procedures and neurosurgeons not specializing in spinal procedures were analyzed before and after implementation of the outpatient surgery protocol. Results Of 1011 cases identified, 643 cases of lumbar discectomy were performed before the implementation of the protocol, and 368 cases were performed after implementation. The admission rate before the start date of the outpatient protocol was 96.4% versus 50.3% after implementation. After protocol implementation, the most common reasons for admission were uncontrolled pain (18.9%), late operative start times (14.1%), comorbidities (13%), and intraoperative operating room complications (11.9%). Intraoperative complications consisted almost exclusively of dural tears. The 30-day readmission rate after protocol initiation was 4.6% ( n = 17 of 368) versus 2.3% ( n = 15 of 643) before initiation ( P = 0.046), and ED visit rate not requiring an admission was 2.2% ( n = 8 of 368) versus 1.1% ( n = 7 of 643) before initiation ( P = 0.170). Conclusions Our data demonstrate that a collaborative protocol for outpatient discectomy can be implemented in a safe and effective manner despite a statistical increase in hospital readmissions. The percentage rates of readmissions and ED visits accounted for a very small percentage of the overall number of cases after protocol implementation. Improvements in perioperative pain management and ensuring that outpatient lumbar discectomies are scheduled early in the day may further decrease the number of admissions. Future studies should examine the societal and financial impact of same-day discectomy versus overnight hospital stays.

Intervertebral disc degeneration is implicated as a major cause of low-back pain. There is a pressing need for new regenerative therapies for disc degeneration that restore native tissue structure and mechanical function. To that end we investigated the therapeutic potential of an injectable, triple-interpenetrating-network hydrogel comprised of dextran, chitosan, and teleostean, for functional regeneration of the nucleus pulposus (NP) of the intervertebral disc in a series of biomechanical, cytotoxicity, and tissue engineering studies. Biomechanical properties were evaluated as a function of gelation time, with the hydrogel reaching ∼90% of steady-state aggregate modulus within 10 h. Hydrogel mechanical properties evaluated in confined and unconfined compression were comparable to native human NP properties. To confirm containment within the disc under physiological loading, toluidine-blue-labeled hydrogel was injected into human cadaveric spine segments after creation of a nucleotomy defect, and the segments were subjected to 10,000 cycles of loading. Gross analysis demonstrated no implant extrusion, and further, that the hydrogel interdigitated well with native NP. Constructs were next surface-seeded with NP cells and cultured for 14 days, confirming lack of hydrogel cytotoxicity, with the hydrogel maintaining NP cell viability and promoting proliferation. Next, to evaluate the potential of the hydrogel to support cell-mediated matrix production, constructs were seeded with mesenchymal stem cells (MSCs) and cultured under prochondrogenic conditions for up to 42 days. Importantly, the hydrogel maintained MSC viability and promoted proliferation, as evidenced by increasing DNA content with culture duration. MSCs differentiated along a chondrogenic lineage, evidenced by upregulation of aggrecan and collagen II mRNA, and increased GAG and collagen content, and mechanical properties with increasing culture duration. Collectively, these results establish the therapeutic potential of this novel hydrogel for functional regeneration of the NP. Future work will confirm the ability of this hydrogel to normalize the mechanical stability of cadaveric human motion segments, and advance the material toward human translation using preclinical large-animal models.

Circumferential decompression has been demonstrated to be the first-line therapy for patients with metastatic tumors in the thoracic spine requiring surgical intervention. However, there is significant debate regarding whether these tumors are best accessed anteriorly utilizing a thoracotomy or posteriorly. We used decision analysis to determine which approach yields greater health-related quality of life (QOL). We searched Medline, Embase, and the Cochrane Library for relevant articles published between 1990 and 2011 on anterior and posterior approaches to metastatic disease in the thoracic spine. QOL values for major treatment outcomes were determined using the existing literature. Separate models were created for ambulatory and nonambulatory patients. A Monte Carlo simulation and sensitivity analyses were used to determine which treatment strategy resulted in the highest QOL. For ambulatory patients, an anterior approach resulted in a slightly higher QOL, and for nonambulatory patients, a posterior approach was favored, but these differences were not statistically significant. Using a decision-analytic model, we found no significant difference in QOL resulting from anterior versus posterior approaches to metastatic lesions in the thoracic spine. Decisions should instead be based on surgeon comfort, tumor characteristics, anatomy of the lesion, patient-related factors, and goals of the operation.

Mucopolysaccharidosis (MPS) VII is a lysosomal storage disorder characterized by deficient activity of β-glucuronidase, leading to progressive accumulation of incompletely degraded heparan, dermatan, and chondroitin sulfate glycosaminoglycans (GAGs). Patients with MPS VII exhibit progressive skeletal deformity including kyphoscoliosis and joint dysplasia, which decrease quality of life and increase mortality. Previously, using the naturally-occurring canine model, we demonstrated that one of the earliest skeletal abnormalities to manifest in MPS VII is failed initiation of secondary ossification in vertebrae and long bones at the requisite postnatal developmental stage. The objective of this study was to obtain global insights into the molecular mechanisms underlying this failed initiation of secondary ossification. Epiphyseal tissue was isolated postmortem from the vertebrae of control and MPS VII-affected dogs at 9 and 14 days-of-age (n = 5 for each group). Differences in global gene expression across this developmental window for both cohorts were measured using whole-transcriptome sequencing (RNA-Seq). Principal Component Analysis revealed clustering of samples within each group, indicating clear effects of both age and disease state. At 9 days-of-age, 1375 genes were significantly differentially expressed between MPS VII and control, and by 14 days-of-age, this increased to 4719 genes. A targeted analysis focused on signaling pathways important in the regulation of endochondral ossification was performed, and a subset of gene expression differences were validated using qPCR. Osteoactivin (GPNMB) was the top upregulated gene in MPS VII at both ages. In control samples, temporal changes in gene expression from 9 to 14 days-of-age were consistent with chondrocyte maturation, cartilage resorption, and osteogenesis. In MPS VII samples, however, elements of key osteogenic pathways such as Wnt/β-catenin and BMP signaling were not upregulated during this same developmental window suggesting that important bone formation pathways are not activated. In conclusion, this study represents an important step towards identifying therapeutic targets and biomarkers for bone disease in MPS VII patients during postnatal growth.

e18307 Background: Metastatic spinal cord compression (MSCC) and symptomatic brain metastases (mets) are potential emergencies that demand coordinated multidisciplinary management. Patients (pts) with concerning symptoms are often referred to the Emergency Department (ED) for expedited imaging, but most do not require subsequent ED or inpatient management. Unnecessary ED visits incur substantial cost to the health system and patients, and cause psychosocial stress for patients often near the end-of-life. To improve access to expedited outpatient imaging for high-risk pts and reduce unnecessary ED visits, we developed outpatient rapid MRI protocols and pathways to rule out MSCC and brain mets. Methods: Tailored abbreviated MRI protocols were developed to allow rapid acquisition of brain ( < 13 minutes) and full spine ( < 25 minutes) exams. Dedicated appointments were reserved on the daily MRI schedule. Exams were immediately interpreted and reported by Radiology to the ordering clinician. This pathway was piloted within the Thoracic Oncology group beginning in 10/2018. Results: Referring specialties included Radiation Oncology (50%), Medical Oncology (36%), Pulmonology (7%), and Surgery (7%). For 6 pts who had outpatient rapid brain imaging, median time from order to exam start was 4.3 h (1.8-31) and order to final report 6.8 h (3.2-34.1). Brain mets were found in 4/6 patients. Only 1/4 positive studies required subsequent ED management. For 8 pts referred for rapid spine imaging, median time from order to exam start was 14.4 h (2.2-72.5) and order to final report 16.7 h (4.0-74.4). Only 1 patient was found to have cord compression and required ED/inpatient management. Overall, 86% of patients did not require ED or inpatient admission. 3 pts (all with negative imaging) died a median 13.4 d (1.4-28.3) after order placement. Conclusions: Outpatient rapid MRI protocols facilitate same-day imaging, interpretation, and management, improving care for thoracic oncology pts with new concerning neurologic symptoms and reducing unnecessary ED visits. Future work will expand access beyond Thoracic Oncology and further quantify improvements in cost savings and patient quality of life.

Object Gunshot wounds to the atlantoaxial spine are uncommon injuries and rarely require treatment, as a bullet traversing this segment often results in a fatal injury. Additionally, these injuries are typically biomechanically stable. The authors report a series of 10 patients with gunshot wounds involving the lateral mass and/or bodies of the atlantoaxial complex. Their care is discussed and conclusions are drawn from these cases to identify the optimal treatment for these injuries. Methods A retrospective review was conducted of patients presenting to the emergency rooms of 3 institutions with gunshot wounds involving the atlantoaxial spine. Mechanism of injury and neurological status were obtained, as was the extent of the osteoligamentous, vascular, and neurological injuries. Nonoperative and operative treatment, complications, and clinical and radiographic outcome were recorded. The data were then analyzed to determine the neurological and biomechanical prognosis of these injuries, the utility of the various diagnostic modalities in the acute management of the injuries, and the nature and effectiveness of the nonoperative and operative treatment modalities. Results Ten patients with gunshot wounds involving the lateral mass and/or bodies of the atlantoaxial complex were identified. All but 2 patients sustained a vertebral artery injury. Each patient was evaluated using cervical radiographs, CT scans, and vascular imaging, 8 in the form of digital subtraction angiography and 2 with high-resolution CT angiography. Uncomplicated patients were treated conservatively using cervical collar immobilization, local wound care, and antibiotics. One patient was treated using a halo for instability and 1 underwent posterior fusion following a posterolateral decompression for delayed myelopathy. One patient underwent transoral resection of a bullet fragment. One patient underwent embolization for a symptomatic arteriovenous fistula and a second patient underwent a neck exploration and a jugular vein ligation. None of the patients received anticoagulation therapy. The mean follow-up duration was 13 months. All but 2 patients regained their previous functional status and all ultimately attained a mechanically stable spine. Conclusions These 10 patients represent a rare form of cervical spine penetrating injury. Unilateral gunshot wounds to the atlantoaxial complex are usually stable and the need for acute surgical intervention is rare. Unilateral vertebral artery injury is well tolerated and any information provided by angiography does not alter the acute management of the patient. Vascular complications from gunshot wounds can be managed effectively by endovascular techniques.

Background Digital radiology enhances productivity and results in long-term cost savings. However, the viewing, storage, and sharing of outside imaging studies on compact discs at ambulatory offices and hospitals pose a number of unique challenges to a surgeon's efficiency and clinical workflow. Objective To improve the efficiency and clinical workflow of an academic neurosurgical practice when evaluating patients with outside radiological studies. Methods Open-source software and commercial hardware were used to design and implement a departmental picture archiving and communications system (PACS). Results The implementation of a departmental PACS system significantly improved productivity and enhanced collaboration in a variety of clinical settings. Using published data on the rate of information technology problems associated with outside studies on compact discs, this system produced a cost savings ranging from $6250 to $33600 and from $43200 to $72000 for 2 cohorts, urgent transfer and spine clinic patients, respectively, therefore justifying the costs of the system in less than a year. Conclusion The implementation of a departmental PACS system using open-source software is straightforward and cost-effective and results in significant gains in surgeon productivity when evaluating patients with outside imaging studies.

Object A positive correlation between outcomes and the volume of patients seen by a provider has been supported by numerous studies. Volume-outcome relationships (VORs) have been well documented in the setting of both neurosurgery and trauma care and have shaped regionalization policies to optimize patient outcomes. Several authors have also investigated the correlation between patient volume and cost of care, known as the volume-cost relationship (VCR), with mixed results. The purpose of the present study was to investigate VORs and VCRs in the treatment of common intracranial injuries by testing the hypotheses that outcomes suffer at small-volume centers and costs rise at large-volume centers. Methods The authors performed a cross-sectional cohort study of patients with neurological trauma using the 2006 Nationwide Inpatient Sample, the largest nationally representative all-payer data set. Patients were identified using ICD-9 codes for subdural, subarachnoid, and extradural hemorrhage following injury. Transfers were excluded from the study. In the primary analysis the association between a facility's neurotrauma patient volume and patient survival was tested. Secondary analyses focused on the relationships between patient volume and discharge status as well as between patient volume and cost. Analyses were performed using logistic regression. Results In-hospital mortality in the overall cohort was 9.9%. In-hospital mortality was 14.9% in the group with the smallest volume of patients, that is, fewer than 6 cases annually. At facilities treating 6–11, 12–23, 24–59, and 60+ patients annually, mortality was 8.0%, 8.3%, 9.5%, and 10.0%, respectively. For these groups there was a significantly reduced risk of in-hospital mortality as compared with the group with fewer than 6 annual patients; the adjusted ORs (and corresponding 95% CIs) were 0.45 (0.29–0.68), 0.56 (0.38–0.81), 0.63 (0.44–0.90), and 0.59 (0.41–0.87), respectively. For these same groups (once again using < 6 cases/year as the reference), there were no statistically significant differences in either estimated actual cost or duration of hospital stay. Conclusions A VOR exists in the treatment of neurotrauma, and a meaningful threshold for significantly improved mortality is 6 cases per year. Emergency and interfacility transport policies based on this threshold might improve national outcomes. Cost of care does not differ significantly with patient volume.

Introduction: Both microvascular decompression (MVD) and stereotactic radiosurgery (SRS) have been demonstrated to be effective in treating medically refractory trigeminal neuralgia. However, there is controversy over which one offers more durable pain relief and the patient selection for each treatment. We used a decision analysis model to calculate the health-related quality of life (QOL) for each treatment. Methods: We searched PubMed and the Cochrane Database of Systematic Reviews for relevant articles on MVD or SRS for trigeminal neuralgia published between 2000 and 2015. Using data from these studies, we modeled pain relief and complication outcomes and assigned QOL values. A sensitivity analysis using a Monte Carlo simulation determined which procedure led to the greatest QOL. Results: MVD produced a significantly higher QOL than SRS at a seven-year follow-up. Additionally, MVD patients had a significantly higher rate of complete pain relief and a significantly lower rate of complications and recurrence. Conclusions: With a decision-analytic model, we calculated that MVD provides more favorable outcomes than SRS for the treatment of trigeminal neuralgia.

Spinal conditions related to intervertebral disc (IVD) degeneration cost billions of dollars in the US annually. Despite the prevalence and soaring cost, there is no specific treatment that restores the physiological function of the diseased IVD. Thus, it is vital to develop new treatment strategies to repair the degenerating IVD. Persons with IVD degeneration without back pain or radicular leg pain often do not require any intervention. Only patients with severe back pain related to the IVD degeneration or biomechanical instability are likely candidates for cell therapy. The IVD progressively degenerates with age in humans, and strategies to repair the IVD depend on the stage of degeneration. Cell therapy and cell-based gene therapy aim to address moderate disc degeneration; advanced stage disease may require surgery. Studies involving autologous, allogeneic, and xenogeneic cells have all shown good survival of these cells in the IVD, confirming that the disc niche is an immunologically privileged site, permitting long-term survival of transplanted cells. All of the animal studies reviewed here reported some improvement in disc structure, and 2 studies showed attenuation of local inflammation. Among the 50 studies reviewed, 25 used some type of scaffold, and cell leakage is a consistently noted problem, though some studies showed reduced cell leakage. Hydrogel scaffolds may prevent cell leakage and provide biomechanical support until cells can become established matrix producers. However, these gels need to be optimized to prevent this leakage. Many animal models have been leveraged in this research space. Rabbit is the most frequently used model (28 of 50), followed by rat, pig, and dog. Sheep and goat IVDs resemble those of humans in size and in the absence of notochordal cells. Despite this advantage, there were only 2 sheep and 1 goat studies of 50 studies in this cohort. It is also unclear if a study in large animals is needed before clinical trials since some of the clinical trials proceeded without a study in large animals. No animal studies or clinical trials completely restored IVD structure. However, results suggest cause for optimism. In light of the fact that patients primarily seek medical care for back pain, attenuating local inflammation should be a priority in benchmarks for success. Clinicians generally agree that short-term back pain should be treated conservatively. When interventions are considered, the ideal therapy should also be minimally invasive and concurrent with other procedures such as discography or discectomy. Restoration of tissue structure and preservation of spinal motion are desirable.

Summary Objective The objective of this study was to establish a large animal model that recapitulates the spectrum of intervertebral disc degeneration that occurs in humans and which is suitable for pre-clinical evaluation of a wide range of experimental therapeutics. Design Degeneration was induced in the lumbar intervertebral discs of large frame goats by either intradiscal injection of chondroitinase ABC (ChABC) over a range of dosages (0.1U, 1U or 5U) or subtotal nucleotomy. Radiographs were used to assess disc height changes over 12 weeks. Degenerative changes to the discs and endplates were assessed via magnetic resonance imaging (MRI), semi-quantitative histological grading, microcomputed tomography (μCT), and measurement of disc biomechanical properties. Results Degenerative changes were observed for all interventions that ranged from mild (0.1U ChABC) to moderate (1U ChABC and nucleotomy) to severe (5U ChABC). All groups showed progressive reductions in disc height over 12 weeks. Histological scores were significantly increased in the 1U and 5U ChABC groups. Reductions in T2 and T1ρ, and increased Pfirrmann grade were observed on MRI. Resorption and remodeling of the cortical boney endplate adjacent to ChABC-injected discs also occurred. Spine segment range of motion (ROM) was greater and compressive modulus was lower in 1U ChABC and nucleotomy discs compared to intact. Conclusions A large animal model of disc degeneration was established that recapitulates the spectrum of structural, compositional and biomechanical features of human disc degeneration. This model may serve as a robust platform for evaluating the efficacy of therapeutics targeted towards varying degrees of disc degeneration.

OBJECTIVE As odontoid process fractures become increasingly common in the aging population, a technical understanding of treatment approaches is critical. 3D image guidance can improve the safety of posterior cervical hardware placement, but few studies have explored its utility in anterior approaches. The authors present in a stepwise fashion the technique of odontoid screw placement using the Medtronic O-arm navigation system and describe their initial institutional experience with this surgical approach. METHODS The authors retrospectively reviewed all cases of anterior odontoid screw fixation for Type II fractures at an academic medical center between 2006 and 2015. Patients were identified from a prospectively collected institutional database of patients who had suffered spine trauma. A standardized protocol for navigated odontoid screw placement was generated from the collective experience at the authors' institution. Secondarily, the authors compared collected variables, including presenting symptoms, injury mechanism, surgical complications, blood loss, operative time, radiographically demonstrated nonunion rate, and clinical outcome at most recent follow-up, between navigated and nonnavigated cases. RESULTS Ten patients (three female; mean age 61) underwent odontoid screw placement. Most patients presented with neck pain without a neurological deficit after a fall. O-arm navigation was used in 8 patients. An acute neck hematoma and screw retraction, each requiring surgery, occurred in 2 patients in whom navigation was used. Partial vocal cord paralysis occurred after surgery in one patient in whom no navigation was used. There was no difference in blood loss or operative time with or without navigation. One patient from each group had radiographic nonunion. No patient reported a worsening of symptoms at follow-up (mean duration 9 months). CONCLUSIONS The authors provide a detailed step-by-step guide to the navigated placement of an odontoid screw. Their surgical experience suggests that O-arm–assisted odontoid screw fixation is a viable approach. Future studies will be needed to rigorously compare the accuracy and efficiency of navigated versus nonnavigated odontoid screw placement.

Although the incidence of neurologic injury in deformity surgery is low, the repercussions are devastating; therefore, every measure available should be adopted to minimize that risk. Advances in instrumentation have been paralleled by the development and improved understanding of intraoperative neurophysiological monitoring which enables lower morbidity in increasingly complex surgeries. Currently, multimodality intraoperative neurophysiological monitoring includes somatosensory-evoked potentials, transcranial motor–evoked potentials, triggered electromyographic stimulation, and mixed neurogenic evoked potentials. The combination of these monitoring modalities provides the greatest sensitivity in detecting impending neurologic compromise during deformity surgery.

STUDY DESIGN Investigation of injectable nucleus pulposus (NP) implant. OBJECTIVE To assess the ability of a recently developed injectable hydrogel implant to restore nondegenerative disc mechanics through support of NP functional mechanics. SUMMARY OF BACKGROUND DATA Although surgical intervention for low back pain is effective for some patients, treated discs undergo altered biomechanics and adjacent levels are at increased risk for accelerated degeneration. One potential treatment as an alternative to surgery for degenerated disc includes the percutaneous delivery of agents to support NP functional mechanics. The implants are delivered in a minimally invasive fashion, potentially on an outpatient basis, and do not preclude later surgical options. One of the challenges in designing such implants includes the need to match key NP mechanical behavior and mimic the role of native nondegenerate NP in spinal motion. METHODS The oxidized hyaluronic acid gelatin implant material was prepared. In vitro mechanical testing was performed in mature ovine bone-disc-bone units in 3 stages: intact, discectomy, and implantation versus sham. Tested samples were cut axially for qualitative structural observations. RESULTS Discectomy increased axial range of motion (ROM) significantly compared with intact. Hydrogel implantation reduced ROM 17% (P < 0.05) compared with discectomy and returned ROM to intact levels (ROM intact 0.71 mm, discectomy 0.87 mm, postimplantation 0.72 mm). Although ROM for the hydrogel implant group was statistically unchanged compared with the intact disc, ROM for sham discs, which received a discectomy and no implant, was significantly increased compared with intact. The compression and tension stiffness were decreased with discectomy and remained unchanged for both implant and sham groups as expected because the annulus fibrosus was not repaired. Gross morphology images confirmed no ejection of NP implant. CONCLUSION An injectable implant that mimics nondegenerate NP has the potential to return motion segment ROM to normal subsequent to injury.

Study Design. Biomechanics of human intervertebral discs before and after nucleotomy. Objective. To noninvasively quantify the effect of nucleotomy on internal strains under axial compression inexion, neutral, and extension positions, and to determine whether the change in strains depended on degeneration. Summary of Background Data. Herniation and nucleotomy may accelerate the progression of disc degeneration. Removal of nucleus pulposus (NP) tissue has resulted in altered disc mechanics in vitro , including a decrease in internal pressure and an increase in the deformations at physiologically relevant strains. We recently presented a technique to quantify internal disc strains using magnetic resonance imaging (MRI). Methods. Degeneration was quantitatively assessed by the T 1 ρ relaxation time in the NP. Samples were prepared from human levels L3-L4 and/or L4-L5. A 1000-N compressive load was applied while in the magnetic resonance scanner. Nucleotomy was performed by removing 2 g of NP through the posterior-lateral annulusbrosus (AF). The discs were rehydrated, reimaged, and retested. The analyzed parameters include axial deformation, AF radial bulge, and strains. Results. The axial deformation was more compressive after nucleotomy. In the neutral position, the axial deformation after nucleotomy correlated with degeneration (as quantied by T 1 ρ in the NP), with minimal alteration in nondegenerated discs. Nucleotomy altered the radial displacements and strains in the neutral position, such that the inner AF radial bulge decreased and the radial strains were more tensile in the lateral AF and less tensile in the posterior AF. In the bending loading positions the radial strains were not affected by nucleotomy. Conclusion. Nucleotomy alters the internal radial and axial AF strains in the neutral position, which may leave the AF vulnerable to damage and microfractures. In bending, the effects of nucleotomy were minimal, likely due to more of the applied load being directed over the AF. Some of the nucleotomy effects are modulated by degeneration, where the mechanical effect of nucleotomy was magnied in degenerated discs and may further induce mechanical

Forms of convenience voting, including voting-by-mail (VBM), provide citizens the opportunity to cast ballots without being exposed to the information revealed in the final weeks leading up to Election Day. This creates the possibility that informational differences will cause VBM and polling place voters to vote differently. We test this hypothesis by looking at whether the increased use of VBM at the precinct-level relates to candidates' vote shares in the 2008 California presidential primary. An election administration policy in California, in which all voters are assigned to VBM based on an arbitrary threshold of the number of registered voters, is exploited to overcome the identification problem caused by the self-selection of voters into VBM. We show that the use of VBM affects the relative performance of candidates remaining in the race and increases the probability of selecting withdrawn candidates. Our findings have implications both for election administration policy and for the study o...

Dale and Strauss’s (DS) noticeable reminder theory (NRT) of voter mobilization posits that mobilization efforts that are highly noticeable and salient to potential voters, even if impersonal, can be successful. In an innovative experimental design, DS show that text messages substantially boost turnout, challenging previous claims that social connectedness is the key to increasing participation. We replicate DS’s research design and extend it in two key ways. First, whereas the treatment in DS’s experiment was a “warm” text message combined with contact, we test NRT more cleanly by examining the effect of “cold” text messages that are completely devoid of auxiliary interaction. Second, we test an implication of NRT that habitual voters should exhibit the largest treatment effects in lower salience elections whereas casual voters should exhibit the largest treatment effects in higher salience elections. Via these two extensions, we find support for NRT.

The authors examine how changes in perceptions of threat affect individuals’ policy views as well as the political implications of this relationship. They administered a survey experiment to a representative sample of the U.S. population in which they exogenously manipulated individuals’ perceived likelihood of a future terrorist attack on American soil and assessed subsequent changes in support for terrorism-related public policies. They find that reducing perceived threat substantially decreases support for policies intended to combat terrorism and that this effect is concentrated among Democrats who believe another terrorist attack is likely to occur. These results suggest that threat, as part of the larger information environment, can alter partisan divisions on controversial policies.

Object Chronic subdural hematoma (CSDH), a condition much more common in the elderly, presents an increasing challenge as the population ages. Treatment strategies for CSDH include bur-hole craniostomy (BHC), twist-drill craniostomy (TDC), and craniotomy. Decision analysis was used to organize existing data and develop recommendations for effective treatment. Methods A Medline search was used to identify articles about treatment of CSDH. Direct assessment by health care professionals of the relative health impact of common complications and recurrences was used to generate utility values for treatment outcomes. Monte Carlo simulation and sensitivity analyses allowed comparisons across treatment strategies. A second simulation examined whether intraoperative irrigation or postoperative drainage affect the outcomes following BHC. Results On a scale from 0 to 1, the utility of BHC was found to be 0.9608, compared with 0.9202 for TDC (p = 0.001) and 0.9169 for craniotomy (p = 0.006). Sensitivity analysis confirmed the robustness of these values. Craniotomy yielded fewer recurrences, but more frequent and more serious complications than did BHC. There were no significant differences for BHC with or without irrigation or postoperative drainage. Conclusions Bur-hole craniostomy is the most efficient choice for surgical drainage of uncomplicated CSDH. Bur-hole craniostomy balances a low recurrence rate with a low incidence of highly morbid complications. Decision analysis provides statistical and empirical guidance in the absence of well-controlled large trials and despite a confusing range of previously reported morbidity and recurrence.

Background context Rat models with altered loading are used to study disc degeneration and mechano-transduction. Given the prominent role of mechanics in disc function and degeneration, it is critical to measure mechanical behavior to evaluate changes after model interventions. Axial compression mechanics of the rat disc are representative of the human disc when normalized by geometry, and differences between the lumbar and caudal disc have been quantified in axial compression. No study has quantified rat disc torsional mechanics. Purpose Compare the torsional mechanical behavior of rat lumbar and caudal discs, determine the contribution of combined axial load on torsional mechanics, and compare the torsional properties of rat discs to human lumbar discs. Study design Cadaveric biomechanical study. Methods Cyclic torsion without compressive load followed by cyclic torsion with a fixed compressive load was applied to rat lumbar and caudal disc levels. Results The apparent torsional modulus was higher in the lumbar region than in the caudal region: 0.081±0.026 (MPa/°, mean±SD) for lumbar axially loaded; 0.066±0.028 for caudal axially loaded; 0.091±0.033 for lumbar in pure torsion; and 0.056±0.035 for caudal in pure torsion. These values were similar to human disc properties reported in the literature ranging from 0.024 to 0.21MPa/°. Conclusions Use of the caudal disc as a model may be appropriate if the mechanical focus is within the linear region of the loading regime. These results provide support for use of this animal model in basic science studies with respect to torsional mechanics.

Surgical treatment for lower back pain related to degenerative disc disease commonly includes discectomy and spinal fusion. While surgical intervention may provide short-term pain relief, it results in altered biomechanics of the spine and may lead to further degenerative changes in adjacent segments. One non-fusion technique currently being investigated is nucleus pulposus (NP) support via either an injectable hydrogel or tissue engineered construct. A major challenge for either approach is to mimic the mechanical properties of native NP. Here we adopt an unconfined compression testing configuration to assess toe-region and linear-region modulus and Poisson's ratio, key functional parameters for NP replacement. Human NP, experimental biocompatible hydrogel formulations composed of hyaluronic acid (HA), PEG-g-chitosan, and gelatin, and conventional alginate and agarose gels were investigated as injectable NP replacements or tissue engineering scaffolds. Testing consisted of a stress-relaxation experiment of 5% strain increments followed by 5-min relaxation periods to a total of 25% strain. Human NP had an average linear-region modulus of 5.39 +/- 2.56 kPa and a Poisson's ratio of 0.62 +/- 0.15. The modulus and Poisson's ratio are important parameters for evaluating the design of implant materials and scaffolds. The synthetic HA-based hydrogels approximated NP well and may serve as suitable NP implant materials.

Despite the prevalence of disc degeneration and its contributions to low back problems, many current treatments are palliative only and ultimately fail. To address this, nucleus pulposus replacements are under development. Previous work on an injectable hydrogel nucleus pulposus replacement composed of n-carboxyethyl chitosan, oxidized dextran, and teleostean has shown that it has properties similar to native nucleus pulposus, can restore compressive range of motion in ovine discs, is biocompatible, and promotes cell proliferation. The objective of this study was to determine if the hydrogel implant will be contained and if it will restore mechanics in human discs undergoing physiologic cyclic compressive loading. Fourteen human lumbar spine segments were tested using physiologic cyclic compressive loading while intact, following nucleotomy, and again following treatment of injecting either phosphate buffered saline (PBS) (sham, n = 7) or hydrogel (implant, n = 7). In each compressive test, mechanical parameters were measured immediately before and after 10,000 cycles of compressive loading and following a period of hydrated recovery. The hydrogel implant was not ejected from the disc during 10,000 cycles of physiological compression testing and appeared undamaged when discs were bisected following all mechanical tests. For sham samples, creep during cyclic loading increased (+15%) from creep during nucleotomy testing, while for implant samples creep strain decreased (−3%) toward normal. There was no difference in compressive modulus or compressive strains between implant and sham samples. These findings demonstrate that the implant interdigitates with the nucleus pulposus, preventing its expulsion during 10,000 cycles of compressive loading and preserves disc creep within human L5–S1 discs. This and previous studies provide a solid foundation for continuing to evaluate the efficacy of the hydrogel implant.

OBJECT The authors have established a multicenter registry to assess the efficacy and costs of common lumbar spinal procedures using prospectively collected outcomes. Collection of these data requires an extensive commitment of resources from each site. The aim of this study was to determine whether outcomes data from shorter-interval follow-up could be used to accurately estimate long-term outcome following lumbar discectomy. METHODS An observational prospective cohort study was completed at 13 academic and community sites. Patients undergoing single-level lumbar discectomy for treatment of disc herniation were included. SF-36 and Oswestry Disability Index (ODI) data were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. Quality-adjusted life year (QALY) data were calculated using SF-6D utility scores. Correlations among outcomes at each follow-up time point were tested using the Spearman rank correlation test. RESULTS One hundred forty-eight patients were enrolled over 1 year. Their mean age was 46 years (49% female). Eleven patients (7.4%) required a reoperation by 1 year postoperatively. The overall 1-year follow-up rate was 80.4%. Lumbar discectomy was associated with significant improvements in ODI and SF-36 scores (p < 0.0001) and with a gain of 0.246 QALYs over the 1-year study period. The greatest gain occurred between baseline and 3-month follow-up and was significantly greater than improvements obtained between 3 and 6 months or 6 months and 1 year(p < 0.001). Correlations between 3-month, 6-month, and 1-year outcomes were similar, suggesting that 3-month data may be used to accurately estimate 1-year outcomes for patients who do not require a reoperation. Patients who underwent reoperation had worse outcomes scores and nonsignificant correlations at all time points. CONCLUSIONS This national spine registry demonstrated successful collection of high-quality outcomes data for spinal procedures in actual practice. Three-month outcome data may be used to accurately estimate outcome at future time points and may lower costs associated with registry data collection. This registry effort provides a practical foundation for the acquisition of outcome data following lumbar discectomy.

[reaction: see text] The Yb(OTf)3-catalyzed annulation reactions of phenols with 5-alkylidene Meldrum's acids enabled the synthesis of structurally diverse heterocycles in high isolated yields. A series of 4-substituted 3,4-dihydrocoumarins, 2,2-disubstituted 4-chromanones, coumarins, and 2-substituted chromones were readily and efficiently assembled, including the naturally occurring coumarins citropten, scoparone, and ayapin. Addition of phenols to biselectrophilic 5-alkylidene Meldrum's acids proceeded through two distinct multibond-forming modes: Friedel-Crafts C-alkylation/O-acylation and Friedel-Crafts C-acylation/O-alkylation. The regioselectivity of the catalytic annulation reaction was controlled by the degree of substitution on the alkylidene moiety.

Fluid condensed from the breath of patients with acute asthma is acidic. Several features of asthma pathophysiology can be initiated by exposure of the airway to acid. In renal tubular epithelium, glutaminase produces ammonia to buffer urinary acid excretion. We hypothesized that human airway epithelium could also express glutaminase. Here, we demonstrate that human airway epithelial cells in vitro have biochemical evidence for glutaminase activity and express mRNA for two glutaminase isoforms (KGA and GAC). Glutaminase activity increased in response to acidic stress (media pH 5.8) and was associated with both increased culture medium pH and improved cell survival. In contrast, activity was inhibited by interferon-gamma and tumor necrosis factor-alpha. Glutaminase protein was expressed in the human airway in vivo. Further, ammonia levels in the breath condensate of subjects with acute asthma were low (30 microM [range: 0-233], n = 18, age 23 +/- 2.5 yr) compared with control subjects (327 microM [14-1,220], n = 24, age 24 +/- 2.4 yr, p < 0.001), and correlated with condensate pH (r = 0.58, p < 0.001). These data demonstrate that glutaminase is expressed and active in the human airway epithelium and may be relevant both to the regulation of airway pH and to the pathophysiology of acute asthmatic airway inflammation.

Degeneration of the intervertebral discs is strongly implicated as a cause of low back pain. Since current treatments for discogenic low back pain show poor long-term efficacy, a number of new, biological strategies are being pursued. For such therapies to succeed, it is critical that they be validated in conditions that mimic the unique biochemical microenvironment of the nucleus pulposus (NP), which include low oxygen tension. Therefore, the objective of this study was to investigate the effects of oxygen tension on NP cell functional extracellular matrix elaboration in 3D culture. Bovine NP cells were encapsulated in agarose constructs and cultured for 14 or 42 days in either 20% or 2% oxygen in defined media containing transforming growth factor beta-3. At each time point, extracellular matrix composition, biomechanics and mRNA expression of key phenotypic markers were evaluated. Results showed that while bulk mechanics and composition were largely independent of oxygen level, low oxygen promoted improved restoration of the NP phenotype, higher mRNA expression of extracellular matrix and NP specific markers, and more uniform matrix elaboration. These findings indicate that culture under physiological oxygen levels is an important consideration for successful development of cell and growth factor-based regenerative strategies for the disc.

Object There is significant practice variation and uncertainty as to the value of surgical treatments for lumbar spine disorders. The authors' aim was to establish a multicenter registry to assess the efficacy and costs of common lumbar spinal procedures by using prospectively collected outcomes. Methods An observational prospective cohort study was completed at 13 academic and community sites. Patients undergoing single-level fusion for spondylolisthesis or single-level lumbar discectomy were included. The 36-Item Short Form Health Survey (SF-36) and Oswestry Disability Index (ODI) data were obtained preoperatively and at 1, 3, 6, and 12 months postoperatively. Power analysis estimated a sample size of 160 patients: lumbar disc (125 patients) and lumbar listhesis (35 patients). The quality-adjusted life year (QALY) data were calculated using 6-dimension utility index scores. Direct costs and complication costs were estimated using Medicare reimbursement values from 2011, and indirect costs were estimated using the human capital approach with the 2011 US national wage index. Total costs equaled $14,980 for lumbar discectomy and $43,852 for surgery for lumbar spondylolisthesis. Results There were 198 patients enrolled over 1 year. The mean age was 46 years (49% female) for lumbar discectomy (n = 148) and 58.1 years (60% female) for lumbar spondylolisthesis (n = 50). Ten patients with disc herniation (6.8%) and 1 with listhesis (2%) required repeat operation at 1 year. The overall 1-year follow-up rate was 88%. At 30 days, both lumbar discectomy and single-level fusion procedures were associated with significant improvements in ODI, visual analog scale, and SF-36 scores (p = 0.0002), which persisted at the 1-year evaluation (p < 0.0001). By 1 year, more than 80% of patients in each cohort who were working preoperatively had returned to work. Lumbar discectomy was associated with a gain of 0.225 QALYs over the 1-year study period ($66,578/QALY gained). Lumbar spinal fusion for Grade I listhesis was associated with a gain of 0.195 QALYs over the 1-year study period ($224,420/QALY gained). Conclusions This national spine registry demonstrated successful collection of high-quality outcomes data for spinal procedures in actual practice. These data are useful for demonstrating return to work and cost-effectiveness following surgical treatment of single-level lumbar disc herniation or spondylolisthesis. One-year cost per QALY was obtained, and this cost per QALY is expected to improve further by 2 years. This work sets the stage for real-world analysis of the value of health interventions.

Mucopolysaccharidosis I (MPS I) is a lysosomal storage disease characterized by deficient α-L-iduronidase activity, leading to the accumulation of poorly degraded glycosaminoglycans (GAGs). Children with MPS I exhibit high incidence of spine disease, including accelerated disc degeneration and vertebral dysplasia, which in turn lead to spinal cord compression and kyphoscoliosis. In this study we investigated the efficacy of neonatal enzyme replacement therapy (ERT), alone or in combination with oral simvastatin (ERT + SIM) for attenuating cervical spine disease progression in MPS I, using a canine model. Four groups were studied: normal controls; MPS I untreated; MPS I ERT-treated; and MPS I ERT + SIM-treated. Animals were euthanized at age 1 year. Intervertebral disc condition and spinal cord compression were evaluated from magnetic resonance imaging (MRI) images and plain radiographs, vertebral bone condition and odontoid hypoplasia were evaluated using micro-computed tomography (µCT), and epiphyseal cartilage to bone conversion was evaluated histologically. Untreated MPS I animals exhibited more advanced disc degeneration and more severe spinal cord compression than normal animals. Both treatment groups resulted in partial preservation of disc condition and cord compression, with ERT + SIM not significantly better than ERT alone. Untreated MPS I animals had significantly lower vertebral trabecular bone volume and mineral density, whereas ERT treatment resulted in partial preservation of these properties. ERT + SIM treatment demonstrated similar, but not greater, efficacy. Both treatment groups partially normalized endochondral ossification in the vertebral epiphyses (as indicated by absence of persistent growth plate cartilage), and odontoid process size and morphology. These results indicate that ERT begun from a very early age attenuates the severity of cervical spine disease in MPS I, particularly for the vertebral bone and odontoid process, and that additional treatment with simvastatin does not provide a significant additional benefit over ERT alone.