In vivo effects of cell seeding technique in an ex vivo regional gene therapy model for bone regeneration.

When delivering cells on a scaffold to treat a bone defect, the cell seeding technique determines the number and distribution of cells within a scaffold, however the optimal technique has not been established. This study investigated if human adipose-derived stem cells (ASCs) transduced with a lentiviral vector to overexpress bone morphogenetic protein 2 (BMP-2) and loaded on a scaffold using dynamic orbital shaker could reduce the total cell dose required to heal a critical sized bone defect when compared with static seeding. Human ASCs were loaded onto a collagen/biphasic ceramic scaffold using static loading and dynamic orbital shaker techniques, compared with our labs standard loading technique, and implanted into femoral defects of nude rats. Both a low dose and standard dose of transduced cells were evaluated. Outcomes investigated included BMP-2 production, radiographic healing, micro-computerized tomography, histologic assessment, and biomechanical torsional testing. BMP-2 production was higher in the orbital shaker cohort compared with the static seeding cohort. No statistically significant differences were noted in radiographic, histomorphometric, and biomechanical outcomes between the low-dose static and dynamic seeding groups, however the standard-dose static seeding cohort had superior biomechanical properties. The standard-dose 5 million cell dose standard loading cohort had superior maximum torque and torsional stiffness on biomechanical testing. The use of orbital shaker technique was labor intensive and did not provide equivalent biomechanical results with the use of fewer cells.

The Effect of Osteoporosis on Complications and Reoperation Rates After Surgical Management of Adult Thoracolumbar Spinal Deformity: A Systematic Review and Meta Analysis.

STUDY DESIGN: Systematic Review. OBJECTIVES: While substantial research has explored the impact of osteoporosis on patients undergoing adult spinal deformity (ASD) correction, the literature remains inconclusive. As such, the purpose of this study is to synthesize and analyze existing studies pertaining to osteoporosis as a predictor of postoperative outcomes in ASD surgery. METHODS: We performed a systematic review and meta-analysis to determine the effect that a diagnosis of osteoporosis, based on ICD-10 coding, dual-energy X-ray absorptiometry (DEXA) or computed tomography, has on the incidence of adverse outcomes following surgical correction of ASD. Statistical analysis was performed using Comprehensive Meta-Analysis (Version 2) using a random effects model to account for heterogeneity between studies. RESULTS: After application of inclusion and exclusion criteria, 36 and 28 articles were included in the systematic review and meta-analysis, respectively. The meta-analysis identified greater rates of screw loosening amongst osteoporotic patients (70.5% vs 31.9%, P = .009), and decreased bone mineral density in patients who developed proximal junctional kyphosis (PJK) (.69 vs .79 g/cm2, P = .001). The systematic review demonstrated significantly increased risk of any complication, reoperation, and proximal junctional failure (PJF) associated with reduced bone density. No statistical difference was observed between groups regarding fusion rates, readmission rates, and patient-reported and/or functional outcome scores. CONCLUSION: This study demonstrates a higher incidence of screw loosening, PJK, and revision surgery amongst osteoporotic ASD patients. Future investigations should explore outcomes at various follow-up intervals in order to better characterize how risk changes with time and to tailor preoperative planning based on patient-specific characteristics.

Systematic Review and Meta-Analysis of the Effect of Osteoporosis on Fusion Rates and Complications Following Surgery for Degenerative Cervical Spine Pathology.

BACKGROUND: As the elderly population grows, the increasing prevalence of osteoporosis presents a unique challenge for surgeons. Decreased bone strength and quality are associated with hardware failure and impaired bone healing, which may increase the rate of revision surgery and the development of complications. The purpose of this review is to determine the impact of osteoporosis on postoperative outcomes for patients with cervical degenerative disease or deformity. METHODS: A systematic review using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Medical Subject Headings terms involving spine surgery for cervical degenerative disease and osteoporosis were performed. This review focused on radiographic outcomes, as well as surgical and medical complications. RESULTS: There were 16 studies included in the degenerative group and 9 in the deformity group. Across degenerative studies, lower bone mineral density was associated with increased rates of cage subsidence in osteoporotic patients undergoing operative treatment for cervical degenerative disease. Most studies reported varied results on the relationship between osteoporosis and other outcomes such as revision and readmission rates, costs, and perioperative complications. Our meta-analysis suggests that osteoporotic patients carry a greater risk of reduced fusion rates at 6 months and 1 year postoperatively. With respect to cervical deformity correction, although individual complication rates were unchanged with osteoporosis, the collective risk of incurring any complication may be increased in patients with poor bone stock. CONCLUSIONS: Overall, the literature suggests that outcomes for osteoporotic patients after cervical spine surgery are multifactorial. Osteoporosis seems to be a significant risk factor for developing cage subsidence and pseudarthrosis postoperatively, whereas reports on medical and hospital-related metrics were inconclusive. Our findings highlight the challenges of caring for osteoporotic patients and underline the need for adequately powered studies to understand how osteoporosis changes the risk index of patients undergoing cervical spine surgery. CLINICAL RELEVANCE: In patients undergoing cervical spine surgery for degenerative disease, osteoporosis is a significant risk factor for long-term postoperative complications-notably cage subsidence and pseudarthrosis. Given the elective nature of these procedures, interdisciplinary collaboration between providers should be routinely implemented to enable medical optimization of patients prior to cervical spine surgery.

Vertebral Aneurysmal Bone Cyst Mimicking Osteosarcoma: Case Report and Review of the Literature.

Aneurysmal bone cysts are benign osseous lesions containing blood-filled cavities separated by walls of connective tissue. They can be difficult to identify clinically due to similarities in presentation, imaging, and histology with other pathologies. Specifically, it is important to distinguish these benign lesions from malignant processes, as both surgical and medical management differ. We present the case of a 21-year-old patient who presented with impaired motor and sensory function in his lower extremities. Radiologic findings were concerning for an invasive neoplasm, and the intraoperative frozen section supported this conclusion. However, an additional histological investigation was confirmatory for a diagnosis of an aneurysmal bone cyst. The patient underwent corpectomy, laminectomy, and a posterior spinal fusion, and regained motor and sensory function shortly thereafter. This report details the importance of considering aneurysmal bone cysts in the differential of infiltrative bone lesions, despite their benign nature, as medical and surgical management can vary greatly.

3D-Printing for Critical Sized Bone Defects: Current Concepts and Future Directions.

The management and definitive treatment of segmental bone defects in the setting of acute trauma, fracture non-union, revision joint arthroplasty, and tumor surgery are challenging clinical problems with no consistently satisfactory solution. Orthopaedic surgeons are developing novel strategies to treat these problems, including three-dimensional (3D) printing combined with growth factors and/or cells. This article reviews the current strategies for management of segmental bone loss in orthopaedic surgery, including graft selection, bone graft substitutes, and operative techniques. Furthermore, we highlight 3D printing as a technology that may serve a major role in the management of segmental defects. The optimization of a 3D-printed scaffold design through printing technique, material selection, and scaffold geometry, as well as biologic additives to enhance bone regeneration and incorporation could change the treatment paradigm for these difficult bone repair problems.

Utility of the Simulated Outcomes Following Carotid Artery Laceration Video Data Set for Machine Learning Applications.

Importance: Surgical data scientists lack video data sets that depict adverse events, which may affect model generalizability and introduce bias. Hemorrhage may be particularly challenging for computer vision-based models because blood obscures the scene. Objective: To assess the utility of the Simulated Outcomes Following Carotid Artery Laceration (SOCAL)-a publicly available surgical video data set of hemorrhage complication management with instrument annotations and task outcomes-to provide benchmarks for surgical data science techniques, including computer vision instrument detection, instrument use metrics and outcome associations, and validation of a SOCAL-trained neural network using real operative video. Design, Setting, and Participants: For this quailty improvement study, a total of 75 surgeons with 1 to 30 years' experience (mean, 7 years) were filmed from January 1, 2017, to December 31, 2020, managing catastrophic surgical hemorrhage in a high-fidelity cadaveric training exercise at nationwide training courses. Videos were annotated from January 1 to June 30, 2021. Interventions: Surgeons received expert coaching between 2 trials. Main Outcomes and Measures: Hemostasis within 5 minutes (task success, dichotomous), time to hemostasis (in seconds), and blood loss (in milliliters) were recorded. Deep neural networks (DNNs) were trained to detect surgical instruments in view. Model performance was measured using mean average precision (mAP), sensitivity, and positive predictive value. Results: SOCAL contains 31 443 frames with 65 071 surgical instrument annotations from 147 trials with associated surgeon demographic characteristics, time to hemostasis, and recorded blood loss for each trial. Computer vision-based instrument detection methods using DNNs trained on SOCAL achieved a mAP of 0.67 overall and 0.91 for the most common surgical instrument (suction). Hemorrhage control challenges standard object detectors: detection of some surgical instruments remained poor (mAP, 0.25). On real intraoperative video, the model achieved a sensitivity of 0.77 and a positive predictive value of 0.96. Instrument use metrics derived from the SOCAL video were significantly associated with performance (blood loss). Conclusions and Relevance: Hemorrhage control is a high-stakes adverse event that poses unique challenges for video analysis, but no data sets of hemorrhage control exist. The use of SOCAL, the first data set to depict hemorrhage control, allows the benchmarking of data science applications, including object detection, performance metric development, and identification of metrics associated with outcomes. In the future, SOCAL may be used to build and validate surgical data science models.

Systematic Review of Racial, Socioeconomic, and Insurance Status Disparities in Neurosurgical Care for Intracranial Tumors.

BACKGROUND: The impact of race, socioeconomic status (SES), insurance status, and other social metrics on the outcomes of patients with intracranial tumors has been reported in several studies. However, these findings have not been comprehensively summarized. METHODS: We conducted a PRISMA systematic review of all published articles between 1990 and 2020 that analyzed intracranial tumor disparities, including race, SES, insurance status, and safety-net hospital status. Outcomes measured include access, standards of care, receipt of surgery, extent of resection, mortality, complications, length of stay (LOS), discharge disposition, readmission rate, and hospital charges. RESULTS: Fifty-five studies were included. Disparities in mortality were reported in 27 studies (47%), showing minority status and lower SES associated with poorer survival outcomes in 14 studies (52%). Twenty-seven studies showed that African American patients had worse outcomes across all included metrics including mortality, rates of surgical intervention, extent of resection, LOS, discharge disposition, and complication rates. Thirty studies showed that privately insured patients and patients with higher SES had better outcomes, including lower mortality, complication, and readmission rates. Six studies showed that worse outcomes were associated with treatment at safety-net and/or low-volume hospitals. The influence of Medicare or Medicaid status, or inequities affecting other minorities, was less clearly delineated. Ten studies (18%) were negative for evidence of disparities. CONCLUSIONS: Significant disparities exist among patients with intracranial tumors, particularly affecting patients of African American race and lower SES. Efforts at the hospital, state, and national level must be undertaken to identify root causes of these issues.

Disparities in the Surgical Treatment of Adult Spine Diseases: A Systematic Review.

BACKGROUND: Our goal was to systematically review the literature on racial/ethnic, insurance, and socioeconomic disparities in adult spine surgery in the United States and analyze potential areas for improvement. METHODS: We conducted a database search of literature published between January 1990 and July 2020 using PRISMA guidelines for all studies investigating a disparity in any aspect of adult spine surgery care analyzed based on race/ethnicity, insurance status/payer, or socioeconomic status (SES). RESULTS: Of 2679 articles identified through database searching, 775 were identified for full-text independent review by 3 authors, from which a final list of 60 studies were analyzed. Forty-three studies analyzed disparities based on patient race/ethnicity, 32 based on insurance status, and 8 based on SES. Five studies assessed disparities in access to care, 15 examined surgical treatment, 35 investigated in-hospital outcomes, and 25 explored after-discharge outcomes. Minority patients were less likely to undergo surgery but more likely to receive surgery from a low-volume provider and experience postoperative complications. White and privately insured patients generally had shorter hospital length of stay, were more likely to undergo favorable/routine discharge, and had lower rates of in-hospital mortality. After discharge, white patients reported better outcomes than did black patients. Thirty-three studies (55%) reported no disparities within at least 1 examined metric. CONCLUSIONS: This comprehensive systematic review underscores ongoing potential for health care disparities among adult patients in spinal surgery. We show a need for continued efforts to promote equity and cultural competency within neurologic surgery.

Systematic Review of Racial, Socioeconomic, and Insurance Status Disparities in the Treatment of Pediatric Neurosurgical Diseases in the United States.

BACKGROUND: Increasing light is being shed on how race, insurance, and socioeconomic status (SES) may be related to outcomes from disease in the United States. To better understand the impact of these health care disparities in pediatric neurosurgery, we performed a systematic review of the literature. METHODS: We conducted a systematic review using PRISMA guidelines and MeSH terms involving neurosurgical conditions and racial, ethnic, and SES disparities. Three independent reviewers screened articles and analyzed texts selected for full analysis. RESULTS: Thirty-eight studies were included in the final analysis, of which all but 2 were retrospective database reviews. Thirty-four studies analyzed race, 22 analyzed insurance status, and 13 analyzed SES/income. Overall, nonwhite patients, patients with public insurance, and patients from lower SES were shown to have reduced access to treatment and greater rates of adverse outcomes. Nonwhite patients were more likely to present at an older age with more severe disease, less likely to undergo surgery at a high-volume surgical center, and more likely to experience postoperative morbidity and mortality. Underinsured and publicly insured patients were more likely to experience delay in surgical referral, less likely to undergo surgical treatment, and more likely to experience inpatient mortality. CONCLUSIONS: Health care disparities are present within multiple populations of patients receiving pediatric neurosurgical care. This review highlights the need for continued investigation into identifying and addressing health care disparities in pediatric neurosurgery patients.

Disparities in the Surgical Treatment of Cerebrovascular Pathologies: A Contemporary Systematic Review.

INTRODUCTION: This systematic review analyzes contemporary literature on racial/ethnic, insurance, and socioeconomic disparities within cerebrovascular surgery in the United States to determine areas for improvement. METHODS: We conducted an electronic database search of literature published between January 1990 and July 2020 using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for studies analyzing a racial/ethnic, insurance, or socioeconomic disparity within adult cerebrovascular surgery. RESULTS: Of 2873 articles screened for eligibility by title and abstract, 970 underwent full-text independent review by 3 authors. Twenty-seven additional articles were identified through references to generate a final list of 47 included studies for analysis. Forty-six were retrospective reviews and 1 was a prospective observational cohort study, thereby comprising Levels III and IV of evidence. Studies investigated carotid artery stenting (11/47, 23%), carotid endarterectomy (22/47, 46.8%), mechanical thrombectomy (8/47, 17%), and endovascular aneurysm coiling or surgical aneurysm clipping (20/47, 42.6%). Minority and underinsured patients were less likely to receive surgical treatment. Non-White patients were more likely to experience a postoperative complication, although this significance was lost in some studies using multivariate analyses to account for complication risk factors. White and privately insured patients generally experienced shorter length of hospital stay, had lower rates of in-hospital mortality, and underwent routine discharge. Twenty-five papers (53%) reported no disparities within at least one examined metric. CONCLUSIONS: This comprehensive contemporary systematic review demonstrates the existence of disparity gaps within the field of adult cerebrovascular surgery. It highlights the importance of continued investigation into sources of disparity and efforts to promote equity within the field.

Use of surgical video-based automated performance metrics to predict blood loss and success of simulated vascular injury control in neurosurgery: a pilot study.

OBJECTIVE: Experts can assess surgeon skill using surgical video, but a limited number of expert surgeons are available. Automated performance metrics (APMs) are a promising alternative but have not been created from operative videos in neurosurgery to date. The authors aimed to evaluate whether video-based APMs can predict task success and blood loss during endonasal endoscopic surgery in a validated cadaveric simulator of vascular injury of the internal carotid artery. METHODS: Videos of cadaveric simulation trials by 73 neurosurgeons and otorhinolaryngologists were analyzed and manually annotated with bounding boxes to identify the surgical instruments in the frame. APMs in five domains were defined-instrument usage, time-to-phase, instrument disappearance, instrument movement, and instrument interactions-on the basis of expert analysis and task-specific surgical progressions. Bounding-box data of instrument position were then used to generate APMs for each trial. Multivariate linear regression was used to test for the associations between APMs and blood loss and task success (hemorrhage control in less than 5 minutes). The APMs of 93 successful trials were compared with the APMs of 49 unsuccessful trials. RESULTS: In total, 29,151 frames of surgical video were annotated. Successful simulation trials had superior APMs in each domain, including proportionately more time spent with the key instruments in view (p < 0.001) and less time without hemorrhage control (p = 0.002). APMs in all domains improved in subsequent trials after the participants received personalized expert instruction. Attending surgeons had superior instrument usage, time-to-phase, and instrument disappearance metrics compared with resident surgeons (p < 0.01). APMs predicted surgeon performance better than surgeon training level or prior experience. A regression model that included APMs predicted blood loss with an R2 value of 0.87 (p < 0.001). CONCLUSIONS: Video-based APMs were superior predictors of simulation trial success and blood loss than surgeon characteristics such as case volume and attending status. Surgeon educators can use APMs to assess competency, quantify performance, and provide actionable, structured feedback in order to improve patient outcomes. Validation of APMs provides a benchmark for further development of fully automated video assessment pipelines that utilize machine learning and computer vision.

A systematic review of paraneoplastic syndromes associated with thymoma: Treatment modalities, recurrence, and outcomes in resected cases.

OBJECTIVE: Paraneoplastic syndromes associated with thymomas remain incompletely understood. The objective was to examine the association between surgically resected thymomas and paraneoplastic syndromes over the past half century. METHODS: A primary PubMed/MEDLINE search was used to identify published articles describing paraneoplastic syndromes associated with thymomas from 1960 to 2019. A secondary search identified additional articles referenced in the articles found in the primary search. Kaplan-Meier and log-rank test were used for time-to-event data analyses. RESULTS: From 407 articles describing 507 patients, 123 different paraneoplastic syndromes were associated with thymoma. The 5 most common paraneoplastic syndromes were myasthenia gravis, pure red cell aplasia, lichen planus, Good syndrome, and limbic encephalitis. Complete or partial resolution of paraneoplastic syndrome symptoms after surgery was noted in 76% of patients, of whom 21% had a relapse or new paraneoplastic syndrome onset after surgery. The most common adjunctive therapy associated with resolution of paraneoplastic syndrome was corticosteroids (30%). For all patients after surgery, thymoma recurrence was observed in 17% of cases, whereas recurrence of paraneoplastic syndrome was observed in 34% of cases, and both were observed in approximately 11% of cases. The 5- and 10-year overall survivals were 78% and 66%, respectively. Improved overall survival was associated with patients who had total resolution from paraneoplastic syndrome. CONCLUSIONS: A comprehensive assessment of publications over the past half century suggests that a multimodal treatment approach that includes surgical resection of thymomas is able to achieve paraneoplastic syndrome resolution in a majority of patients. Onset of new paraneoplastic syndromes after surgery is associated with the recurrence of the first paraneoplastic syndrome, and resolution of paraneoplastic syndrome is associated with improved overall survival.