Gene Therapy and Spinal Fusion: Systematic Review and Meta-Analysis of the Available Data.

OBJECTIVE: To analyze the extant literature describing the application of gene therapy to spinal fusion. METHODS: A systematic review of the English-language literature was performed. The search query was designed to include all published studies examining gene therapy approaches to promote spinal fusion. Approaches were classified as ex vivo (delivery of genetically modified cells) or in vivo (delivery of growth factors via vectors). The primary endpoint was fusion rate. Random effects meta-analyses were performed to calculate the overall odds ratio (OR) of fusion using a gene therapy approach and overall fusion rate. Subgroup analyses of fusion rate were also performed for each gene therapy approach. RESULTS: Of 1179 results, 35 articles met criteria for inclusion (all preclinical), of which 26 utilized ex vivo approaches and 9 utilized in vivo approaches. Twenty-seven articles (431 animals) were included in the meta-analysis. Gene therapy use was associated with significantly higher fusion rates (OR 77; 95% confidence interval {CI}: [31, 192]; P < 0.001); ex vivo strategies had a greater effect (OR 136) relative to in vivo strategies (OR 18) (P = 0.017). The overall fusion rate using a gene therapy approach was 80% (95% CI: [62%, 93%]; P < 0.001); overall fusion rates were significantly higher in subjects treated with ex vivo compared to in vivo strategies (90% vs. 42%; P = 0.011). For both ex vivo and in vivo approaches, the effect of gene therapy on fusion was independent of animal model. CONCLUSIONS: Gene therapy may augment spinal fusion; however, future investigation in clinical populations is necessary.

Perioperative Blindness in Spine Surgery: A Scoping Literature Review.

Perioperative vision loss (POVL) is a devastating surgical complication that impacts both the recovery from surgery and quality of life, most commonly occurring after spine surgery. With rates of spine surgery dramatically increasing, the prevalence of POVL will increase proportionately. This scoping review aims to aggregate the literature pertinent to POVL in spine surgery and consolidate recommendations and preventative measures to reduce the risk of POVL. There are several causes of POVL, and the main contribution following spine surgery is ischemic optic neuropathy (ION). Vision loss often manifests immediately following surgery and is irreversible and severe. Diffusion weighted imaging has recently surfaced as a diagnostic tool to identify ION. There are no effective treatments; therefore, risk stratification for counseling and prevention are vital. Patients undergoing prone surgery of long duration and/or with significant expected blood loss are at greatest risk. Future research is necessary to develop effective treatments.

Scoping review on the state of racial disparities literature in the treatment of neurosurgical disease: a call for action.

OBJECTIVE: Racial disparities are ubiquitous across medicine in the US. This study aims to assess the evidence of racial disparities within neurosurgery and across its subspecialties, with a specific goal of quantifying the distribution of articles devoted to either identifying, understanding, or reducing disparities. METHODS: The authors searched the MEDLINE, EMBASE, and Scopus databases by using keywords to represent the concepts of neurosurgery, patients, racial disparities, and specific study types. Two independent reviewers screened the article titles and abstracts for relevance. A third reviewer resolved conflicts. Data were then extracted from the included articles and each article was categorized into one of three phases: identifying, understanding, or reducing disparities. This review was conducted in accordance with the PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines. RESULTS: Three hundred seventy-one studies published between 1985 and 2023 were included. The distribution of racial disparities literature was not equally spread among specialties, with spine representing approximately 48.3% of the literature, followed by tumor (22.1%) and general neurosurgery (12.9%). Most studies were dedicated to identifying racial disparities (83.6%). The proportion of literature devoted to understanding and reducing disparities was much lower (15.1% and 1.3%, respectively). Black patients were the most negatively impacted racial/ethnic group in the review (63.3%). The Hispanic or Latino ethnic group was the second most negatively impacted (25.1%). The following categories-other outcomes (28.0%), the offering of treatment (21.6%), complications (18.6%), and survival (16.7%)-represented the most frequently measured outcomes. CONCLUSIONS: Although strides have been taken to identify racial disparities within neurosurgery, fewer studies have focused on understanding and reducing these disparities. The tremendous rise of literature within this domain but the relative paucity of solutions necessitates the study of targeted interventions to provide equitable care for all patients undergoing neurosurgical treatment.

Robotic-Assisted Minimally Invasive Spinopelvic Fixation for Traumatic Sacral Fractures: Case Series Investigating Early Safety and Efficacy.

BACKGROUND: High-energy traumatic sacral fractures, particularly U-type or AOSpine classification type C fractures, may lead to significant functional deficits. Traditionally, spinopelvic fixation for unstable sacral fractures was performed with open reduction and fixation, but robotic-assisted minimally invasive surgical methods now present new, less invasive approaches. The objective here was to present a series of patients with traumatic sacral fractures treated with robotic-assisted minimally invasive spinopelvic fixation and discuss early experience, considerations, and technical challenges. METHODS: Between June 2022 and January 2023, 7 consecutive patients met the inclusion criteria. Intraoperative fluoroscopic images were merged with intraoperative computed tomography images using a robotic system to plan the trajectories for placement of bilateral lumbar pedicle and iliac screws. Intraoperative computed tomography was performed after pedicle and pelvic screw insertion to confirm appropriate placement before insertion of rods percutaneously without the need for a side connector. RESULTS: The cohort consisted of 7 patients (4 female, 3 male) with ages ranging from 20 to 74. Intraoperatively, the mean blood loss was 85.7 ± 84.0 mL, and mean operative time was 178.4 ± 63.9 minutes. There were no complications in 6 patients; 1 patient experienced both a medially breached pelvic screw and a complicated rod pullout. All patients were safely discharged to their homes or an acute rehabilitation facility. CONCLUSIONS: Our early experience reveals that robotic-assisted minimally invasive spinopelvic fixation for traumatic sacral fractures is a safe and feasible treatment option with the potential to improve outcomes and reduce complications.

Characteristics of patients who return to work after undergoing surgery for cervical spondylotic myelopathy: a Quality Outcomes Database study.

OBJECTIVE: Return to work (RTW) is an important surgical outcome for patients who are employed, yet a significant number of patients with cervical spondylotic myelopathy (CSM) who are employed undergo cervical spine surgery and fail to RTW. In this study, the authors investigated factors associated with failure to RTW in the CSM population who underwent cervical spine surgery and who were considered to have a good surgical outcome yet failed to RTW. METHODS: This study retrospectively analyzed prospectively collected data from the cervical myelopathy module of a national spine registry, the Quality Outcomes Database. The CSM data set of the Quality Outcomes Database was queried for patients who were employed at the time of surgery and planned to RTW postoperatively. Distinct multivariable logistic regression models were fitted with 3-month RTW as an outcome for the overall population to identify risk factors for failure to RTW. Good outcomes were defined as patients who had no adverse events (readmissions or complications), who had achieved 30% improvement in Neck Disability Index score, and who were satisfied (North American Spine Society satisfaction score of 1 or 2) at 3 months postsurgery. RESULTS: Of the 409 patients who underwent surgery, 80% (n = 327) did RTW at 3 months after surgery. At 3 months, 56.9% of patients met the criteria for a good surgical outcome, and patients with a good outcome were more likely to RTW (88.1% vs 69.2%, p < 0.01). Of patients with a good outcome, 11.9% failed to RTW at 3 months. Risk factors for failing to RTW despite a good outcome included preoperative short-term disability or leave status (OR 3.03 [95% CI 1.66-7.90], p = 0.02); a higher baseline Neck Disability Index score (OR 1.41 [95% CI 1.09-1.84], p < 0.01); and higher neck pain score at 3 months postoperatively (OR 0.81 [95% CI 0.66-0.99], p = 0.04). CONCLUSIONS: Most patients with CSM who undergo spine surgery reenter the workforce within 3 months from surgery, with RTW rates being higher among patients who experience good outcomes. Among patients with good outcomes who were employed, failure to RTW was associated with being on preoperative short-term disability or leave status prior to surgery as well as higher neck pain scores at baseline and at 3 months postoperatively.

Intraoperative localization and "snowman" muscle pledget repair for ventral dural defect in a case of spontaneous intracranial hypotension.

BACKGROUND: This image report with technical notes is the first to illustrate and describe the technique used to treat spinal cerebrospinal fluid (CSF) leaks with the "snowman" muscle pledget. A 49-year-old male presented with orthostatic headaches as well as the left abducens nerve palsy. Patient's workup including findings of diffuse meningeal enhancement on magnetic resonance imaging, lumbar puncture opening pressure of 4 cm H2O, and CT myelogram demonstrating evidence of ventral spinal thoracic CSF leak. CASE DESCRIPTION: Procedure took place in a hybrid biplane operating room so that simultaneous digital subtraction myelogram may also be performed for intraoperative localization. Dural defect was identified intraoperatively and repaired with thoracic laminectomy and "snowman" muscle pledget technique. Postoperatively, the patient did well with resolution of his symptoms. CONCLUSION: The authors have proposed a grading scale to aid in the work up and management of intracranial hypotension. The use of a hybrid biplane operating room and "snowman" muscle pledget technique is a safe and effective technique to treat spontaneous spinal CSF leaks resulting from dural defects.

Comprehensive RNA analysis of CSF reveals a role for CEACAM6 in lung cancer leptomeningeal metastases.

Non-small cell lung cancer (NSCLC) metastatic to the brain leptomeninges is rapidly fatal, cannot be biopsied, and cancer cells in the cerebrospinal fluid (CSF) are few; therefore, available tissue samples to develop effective treatments are severely limited. This study aimed to converge single-cell RNA-seq and cell-free RNA (cfRNA) analyses to both diagnose NSCLC leptomeningeal metastases (LM), and to use gene expression profiles to understand progression mechanisms of NSCLC in the brain leptomeninges. NSCLC patients with suspected LM underwent withdrawal of CSF via lumbar puncture. Four cytology-positive CSF samples underwent single-cell capture (n = 197 cells) by microfluidic chip. Using robust principal component analyses, NSCLC LM cell gene expression was compared to immune cells. Massively parallel qPCR (9216 simultaneous reactions) on human CSF cfRNA samples compared the relative gene expression of patients with NSCLC LM (n = 14) to non-tumor controls (n = 7). The NSCLC-associated gene, CEACAM6, underwent in vitro validation in NSCLC cell lines for involvement in pathologic behaviors characteristic of LM. NSCLC LM gene expression revealed by single-cell RNA-seq was also reflected in CSF cfRNA of cytology-positive patients. Tumor-associated cfRNA (e.g., CEACAM6, MUC1) was present in NSCLC LM patients' CSF, but not in controls (CEACAM6 detection sensitivity 88.24% and specificity 100%). Cell migration in NSCLC cell lines was directly proportional to CEACAM6 expression, suggesting a role in disease progression. NSCLC-associated cfRNA is detectable in the CSF of patients with LM, and corresponds to the gene expression profile of NSCLC LM cells. CEACAM6 contributes significantly to NSCLC migration, a hallmark of LM pathophysiology.

A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2-Induced Glycolytic Reprogramming in Glioblastoma.

PURPOSE: Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel PET tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[18F]fluorophenyl)sulfonyl)-4-((4-methoxyphenyl)sulfonyl)piperazine ([18F]DASA-23) in cell culture, mouse models of GBM, healthy human volunteers, and patients with GBM. EXPERIMENTAL DESIGN: [18F]DASA-23 was synthesized with a molar activity of 100.47 ± 29.58 GBq/µmol and radiochemical purity >95%. We performed initial testing of [18F]DASA-23 in GBM cell culture and human GBM xenografts implanted orthotopically into mice. Next, we produced [18F]DASA-23 under FDA oversight, and evaluated it in healthy volunteers and a pilot cohort of patients with glioma. RESULTS: In mouse imaging studies, [18F]DASA-23 clearly delineated the U87 GBM from surrounding healthy brain tissue and had a tumor-to-brain ratio of 3.6 ± 0.5. In human volunteers, [18F]DASA-23 crossed the intact blood-brain barrier and was rapidly cleared. In patients with GBM, [18F]DASA-23 successfully outlined tumors visible on contrast-enhanced MRI. The uptake of [18F]DASA-23 was markedly elevated in GBMs compared with normal brain, and it identified a metabolic nonresponder within 1 week of treatment initiation. CONCLUSIONS: We developed and translated [18F]DASA-23 as a new tracer that demonstrated the visualization of aberrantly expressed PKM2 for the first time in human subjects. These results warrant further clinical evaluation of [18F]DASA-23 to assess its utility for imaging therapy-induced normalization of aberrant cancer metabolism.

Randomized Controlled Trials in Functional Neurosurgery-Association of Device Approval Status and Trial Quality.

INTRODUCTION: Randomized controlled trials (RCTs) have been critical in evaluating the safety and efficacy of functional neurosurgery interventions. Given this, we sought to systematically assess the quality of functional neurosurgery RCTs. METHODS: We used a database of neurosurgical RCTs (trials published from 1961 to 2016) to identify studies of functional neurosurgical procedures (N = 48). We extracted data on the design and quality of these RCTs and quantified the quality of trials using Jadad scores. We categorized RCTs based on the device approval status at the time of the trial and tested the association of device approval status with trial design and quality parameters. RESULTS: Of the 48 analyzed functional neurosurgery RCTs, the median trial size was 34.5 patients with a median age of 51. The most common indications were Parkinson's disease (N = 20), epilepsy (N = 10), obsessive-compulsive disorder (N = 4), and pain (N = 4). Most trials reported inclusion and exclusion criteria (95.8%), sample size per arm (97.9%), and baseline characteristics of the patients being studied (97.9%). However, reporting of allocation concealment (29.2%), randomization mode (66.7%), and power calculations (54.2%) were markedly less common. We observed that trial quality has improved over time (Spearman r, 0.49). We observed that trials studying devices with humanitarian device exemption (HDE) and experimental indications (EI) tended to be of higher quality than trials of FDA-approved devices (p = 0.011). A key distinguishing quality characteristic was the proportion of HDE and EI trials that were double-blinded, compared to trials of FDA-approved devices (HDE, 83.3%; EI, 69.2%; FDA-approved, 35.3%). Although more than one-third of functional neurosurgery RCTs reported funding from industry, no significant association was identified between funding source and trial quality or outcome. CONCLUSION: The quality of RCTs in functional neurosurgery has improved over time but reporting of specific metrics such as power calculations and allocation concealment requires further improvement. Device approval status but not funding source was associated with trial quality.

Difference-Frequency Ultrasound Imaging With Non-Linear Contrast.

Conventional ultrasound imaging is based on the scattering of sound from inhomogeneities in the density and the speed of sound and is often used in medicine to resolve pathologic compared to normal tissue. Here we demonstrate a difference-frequency ultrasound (dfUS) imaging method that is based on the interaction of two sound pulses that propagate non-collinearly and intersect in space and time. The dfUS signal arises primarily from the second-order non-linear coefficient, a contrast mechanism that differs from linear and harmonic US imaging. The distinct contrast mechanism allows dfUS to image anatomic features that are not identifiable in conventional US images of salmon and pig kidney tissue. Further, dfUS produces enhanced contrast of glioblastoma tumor implanted in the mouse brain, revealing its potential for improving medical diagnosis. Progress towards a real-time system is discussed.

Diffusion tensor magnetic resonance imaging of the optic nerves in pediatric hydrocephalus.

OBJECTIVE: While conventional imaging can readily identify ventricular enlargement in hydrocephalus, structural changes that underlie microscopic tissue injury might be more difficult to capture. MRI-based diffusion tensor imaging (DTI) uses properties of water motion to uncover changes in the tissue microenvironment. The authors hypothesized that DTI can identify alterations in optic nerve microstructure in children with hydrocephalus. METHODS: The authors retrospectively reviewed 21 children (< 18 years old) who underwent DTI before and after neurosurgical intervention for acute obstructive hydrocephalus from posterior fossa tumors. Their optic nerve quantitative DTI metrics of mean diffusivity (MD) and fractional anisotropy (FA) were compared to those of 21 age-matched healthy controls. RESULTS: Patients with hydrocephalus had increased MD and decreased FA in bilateral optic nerves, compared to controls (p < 0.001). Normalization of bilateral optic nerve MD and FA on short-term follow-up (median 1 day) after neurosurgical intervention was observed, as was near-complete recovery of MD on long-term follow-up (median 1.8 years). CONCLUSIONS: DTI was used to demonstrate reversible alterations of optic nerve microstructure in children presenting acutely with obstructive hydrocephalus. Alterations in optic nerve MD and FA returned to near-normal levels on short- and long-term follow-up, suggesting that surgical intervention can restore optic nerve tissue microstructure. This technique is a safe, noninvasive imaging tool that quantifies alterations of neural tissue, with a potential role for evaluation of pediatric hydrocephalus.

Patient Satisfaction and Press Ganey Scores for Spine Versus Nonspine Neurosurgery Clinics.

STUDY DESIGN: Retrospective survey review. OBJECTIVE: We seek to evaluate satisfaction scores in patients seen in neurosurgical spine versus neurosurgical nonspine clinics. SUMMARY OF BACKGROUND DATA: The Press Ganey survey is a well-established metric for measuring hospital performance and patient satisfaction. These measures have important implications in setting hospital policy and guiding interventions to improve patient perceptions of care. METHODS: Retrospective Press Ganey survey review was performed to identify patient demographics and patient visit characteristics from January 1st, 2012 to October 10th, 2017 at Stanford Medical Center. A total of 40 questions from the Press Ganey survey were investigated and grouped in categories addressing physician and nursing care, personal concerns, admission, room, meal, operating room, treatment and discharge conditions, visitor accommodations and overall clinic assessment. Raw ordinal scores were converted to continuous scores of 100 for unpaired student t test analysis. We identified 578 neurosurgical spine clinic patients and 1048 neurosurgical nonspine clinic patients. RESULTS: Spine clinic patients reported lower satisfaction scores in aggregate (88.2 vs. 90.1; P=0.0014), physician (89.5 vs. 92.6; P=0.0002) and nurse care (91.3 vs. 93.4; P=0.0038), personal concerns (88.2 vs. 90.9; P=0.0009), room (81.0 vs. 83.1; P=0.0164), admission (90.8 vs. 92.6; P=0.0154) and visitor conditions (87.0 vs. 89.2; P=0.0148), and overall clinic assessment (92.9 vs. 95.5; P=0.005). CONCLUSIONS: This study is the first to evaluate the relationship between neurosurgical spine versus nonspine clinic with regards to patient satisfaction. The spine clinic cohort reported less satisfaction than the nonspine cohort in all significant questions on the Press Ganey survey. Our findings suggest that efforts should be made to further study and improve patient satisfaction in spine clinics. LEVEL OF EVIDENCE: Level III.

Minimally invasive lumbar pedicle screw fixation using cortical bone trajectory - Screw accuracy, complications, and learning curve in 100 screw placements.

Cortical bone trajectory (CBT) is a novel pedicle insertion technique with comparable or superior mechanical properties and reduced invasiveness compared to traditional methods. We describe the screw accuracy, complications, and learning curve associated with CBT use. A prospective cohort study was performed involving 22 patients who underwent lumbar fusion with CBT screw placement. A total of 100 cortical screws were placed. Post-operative CT scans were reviewed to assess the adequacy of screw placement and calculate the incidence of vertebral body and pedicle breaches from cortical screw placement. Technique-related complications were examined. The entire surgical cohort was divided into two groups: early experience (first 11 patients) and late experience (last 11 patients), to study the effect of learning curve on CBT screw placement. Medial pedicle breach was observed in 6/100 cases and lateral vertebral body breach was observed in 1/100 cases. The incidence of durotomy related to the technique was 4.5% (N = 1/22). Post-surgical wound infection was seen in 9.1% of patients (N = 2/22). 66.7% (N = 4/6) of medial pedicle breaches, 100% (N = 1/1) of lateral breaches, 100% (N = 1/1) of CBT technique-related CSF leaks, and 100% (N = 2/2) of wound infections occurred in the early experience phase of our study (p = 0.0945). A shift in surgical technique and greater efficiency over time decreased the incidence of overall complications in the late cohort. The difference, however, did not reach statistical significance. A lateralized starting point for the cortical screw on the pars interarticularis and use of smaller diameter screws resulted in fewer medial pedicle out-fractures and breaches.

Rapid-sequence brain magnetic resonance imaging for Chiari I abnormality.

OBJECTIVE Fast magnetic resonance imaging (fsMRI) sequences are single-shot spin echo images with fast acquisition times that have replaced CT scans for many conditions. Introduced as a means of evaluating children with hydrocephalus and macrocephaly, these sequences reduce the need for anesthesia and can be more cost-effective, especially for children who require multiple surveillance scans. However, the role of fsMRI has yet to be investigated in evaluating the posterior fossa in patients with Chiari I abnormality (CM-I). The goal of this study was to examine the diagnostic performance of fsMRI in evaluating the cerebellar tonsils in comparison to conventional MRI. METHODS The authors performed a retrospective analysis of 18 pediatric patients with a confirmed diagnosis of CM-I based on gold-standard conventional brain MRI and 30 controls without CM-I who had presented with various neurosurgical conditions. The CM-I patients were included if fsMRI studies had been obtained within 1 year of conventional MRI with no surgical intervention between the studies. Two neuroradiologists reviewed the studies in a blinded fashion to determine the diagnostic performance of fsMRI in detecting CM-I. For the CM-I cohort, the fsMRI and T2-weighted MRI exams were randomized, and the blinded reviewers performed tonsillar measurements on both scans. RESULTS The mean age of the CM-I cohort was 7.39 years, and 50% of these subjects were male. The mean time interval between fsMRI and conventional T2-weighted MRI was 97.8 days. Forty-four percent of the subjects had undergone imaging after posterior fossa decompression. The sensitivity and specificity of fsMRI in detecting CM-I was 100% (95% CI 71.51%-100%) and 92.11% (95% CI 78.62%-98.34%), respectively. If only preoperative patients are considered, both sensitivity and specificity increase to 100%. The authors also performed a cost analysis and determined that fsMRI was significantly cost-effective compared to T2-weighted MRI or CT. CONCLUSIONS Despite known limitations, fsMRI may serve as a useful diagnostic and surveillance tool for CM-I. It is more cost-effective than full conventional brain MRI and decreases the need for sedation in young children.

Single-Cell RNA-Sequencing in Glioma.

PURPOSE OF REVIEW: In this review, we seek to summarize the literature concerning the use of single-cell RNA-sequencing for CNS gliomas. RECENT FINDINGS: Single-cell analysis has revealed complex tumor heterogeneity, subpopulations of proliferating stem-like cells and expanded our view of tumor microenvironment influence in the disease process. Although bulk RNA-sequencing has guided our initial understanding of glioma genetics, this method does not accurately define the heterogeneous subpopulations found within these tumors. Single-cell techniques have appealing applications in cancer research, as diverse cell types and the tumor microenvironment have important implications in therapy. High cost and difficult protocols prevent widespread use of single-cell RNA-sequencing; however, continued innovation will improve accessibility and expand our of knowledge gliomas.

Massive Intradural Chondroma Masquerading as Lower Body Parkinsonism.

Intracranial chondromas of the dural convexity are exceedingly rare with less than 30 reported in the literature to date. We report a massive intradural convexity chondroma in a patient initially thought to have a frontal gait neurodegenerative disorder. This large tumor required a complex, piecemeal surgical resection due to the dense, fibrous nature of the tumor and the proximity of crucial structures. The patient had complete resolution of her preoperative symptoms after surgical excision.

A review of potential applications of MR-guided focused ultrasound for targeting brain tumor therapy.

Magnetic resonance-guided focused ultrasound (MRgFUS) has been used extensively to ablate brain tissue in movement disorders, such as essential tremor. At a lower energy, MRgFUS can disrupt the blood-brain barrier (BBB) to allow passage of drugs. This focal disruption of the BBB can target systemic medications to specific portions of the brain, such as for brain tumors. Current methods to bypass the BBB are invasive, as the BBB is relatively impermeable to systemically delivered antineoplastic agents. Multiple healthy and brain tumor animal models have suggested that MRgFUS disrupts the BBB and focally increases the concentration of systemically delivered antitumor chemotherapy, immunotherapy, and gene therapy. In animal tumor models, combining MRgFUS with systemic drug delivery increases median survival times and delays tumor progression. Liposomes, modified microbubbles, and magnetic nanoparticles, combined with MRgFUS, more effectively deliver chemotherapy to brain tumors. MRgFUS has great potential to enhance brain tumor drug delivery, while limiting treatment toxicity to the healthy brain.

National Trends for Reoperation in Older Patients with Glioblastoma.

BACKGROUND: Despite multimodal therapies extending patient survival, glioblastoma (GBM) recurrence is all but a certainty. To date, there are few single-center studies of reoperations. Our study aimed to assess GBM reoperation trends nationally in older patients, with emphasis on outcomes. METHODS: The linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database was searched to identify patients 66 years and older with GBM from 1997 to 2010. The primary outcome was survival after diagnosis. Kaplan-Meier curves and multivariate analysis with proportional hazard ratios were used. RESULTS: Three thousand nine hundred sixty-three patients with recurrent GBM who initially received a surgical resection were identified (mean age = 74.7 years). Four hundred ninety-six (12%) of the patients with recurrent GBM underwent at least one reoperation at an average of 7.2 months after the initial diagnosis. Reoperation increased survival in patients compared with those who did not have surgical resection (12 vs. 5 months; P < 0.0001; hazard ratio [HR] = 0.666). Within the reoperated cohort, gross total resection improved median survival over subtotal resection (HR = 0.779). Two or more reoperations upon GBM recurrence improved survival to 17 months (P = 0.002). The overall complication rate was 21.7% in the initial resection-only group, versus 20.4% in the 1-reoperation group and 25.3% in the 2-reoperation group. CONCLUSIONS: Although definitive conclusions cannot be made given the lack of granularity, our national database study supports gross total resection as the initial treatment of choice, followed by reoperation at the time of recurrence, if tolerated, even in older patients.

Preoperative depression, lumbar fusion, and opioid use: an assessment of postoperative prescription, quality, and economic outcomes.

OBJECTIVE Preoperative depression has been linked to a variety of adverse outcomes following lumbar fusion, including increased pain, disability, and 30-day readmission rates. The goal of the present study was to determine whether preoperative depression is associated with increased narcotic use following lumbar fusion. Moreover, the authors examined the association between preoperative depression and a variety of secondary quality indicator and economic outcomes, including complications, 30-day readmissions, revision surgeries, likelihood of discharge home, and 1- and 2-year costs. METHODS A retrospective analysis was conducted using a national longitudinal administrative database (MarketScan) containing diagnostic and reimbursement data on patients with a variety of private insurance providers and Medicare for the period from 2007 to 2014. Multivariable logistic and negative binomial regressions were performed to assess the relationship between preoperative depression and the primary postoperative opioid use outcomes while controlling for demographic, comorbidity, and preoperative prescription drug-use variables. Logistic and log-linear regressions were also used to evaluate the association between depression and the secondary outcomes of complications, 30-day readmissions, revisions, likelihood of discharge home, and 1- and 2-year costs. RESULTS The authors identified 60,597 patients who had undergone lumbar fusion and met the study inclusion criteria, 4985 of whom also had a preoperative diagnosis of depression and 21,905 of whom had a diagnosis of spondylolisthesis at the time of surgery. A preoperative depression diagnosis was associated with increased cumulative opioid use (ß = 0.25, p < 0.001), an increased risk of chronic use (OR 1.28, 95% CI 1.17-1.40), and a decreased probability of opioid cessation (OR 0.96, 95% CI 0.95-0.98) following lumbar fusion. In terms of secondary outcomes, preoperative depression was also associated with a slightly increased risk of complications (OR 1.14, 95% CI 1.03-1.25), revision fusions (OR 1.15, 95% CI 1.05-1.26), and 30-day readmissions (OR 1.19, 95% CI 1.04-1.36), although it was not significantly associated with the probability of discharge to home (OR 0.92, 95% CI 0.84-1.01). Preoperative depression also resulted in increased costs at 1 (ß = 0.06, p < 0.001) and 2 (ß = 0.09, p < 0.001) years postoperatively. CONCLUSIONS Although these findings must be interpreted in the context of the limitations inherent to retrospective studies utilizing administrative data, they provide additional evidence for the link between a preoperative diagnosis of depression and adverse outcomes, particularly increased opioid use, following lumbar fusion.

Neurosurgical Randomized Controlled Trials-Distance Travelled.

BACKGROUND: The evidence base for many neurosurgical procedures has been limited. We performed a comprehensive and systematic analysis of study design, quality of reporting, and trial results of neurosurgical randomized controlled trials (RCTs). OBJECTIVE: To systematically assess the design and quality characteristics of neurosurgical RCTs. METHODS: From January 1961 to June 2016, RCTs with >5 patients assessing any 1 neurosurgical procedure against another procedure, nonsurgical treatment, or no treatment were retrieved from MEDLINE, Scopus, and Cochrane Library. RESULTS: The median sample size in the 401 eligible RCTs was 73 patients with a mean patient age of 49.6. Only 111 trials (27.1%) described allocation concealment, 140 (34.6%) provided power calculations, and 117 (28.9%) were adequately powered. Significant efficacy or trend for efficacy was claimed in 226 reports (56.4%), no difference between the procedures was found in 166 trials (41.4%), and significant harm was reported in 9 trials (2.2%). Trials with a larger sample size were more likely to report randomization mode, specify allocation concealment, and power calculations (all P < .001). Government funding was associated with better specification of power calculations (P = .008) and of allocation concealment (P = .026), while industry funding was associated with reporting significant efficacy (P = .02). Reporting of funding, specification of randomization mode and primary outcomes, and mention of power calculations improved significantly (all, P < .05) over time. CONCLUSION: Several aspects of the design and reporting of RCTs on neurosurgical procedures have improved over time. Better powered and accurately reported trials are needed in neurosurgery to deliver evidence-based care and achieve optimal outcomes.