A review of vascular endothelial growth factor and its potential to improve functional outcomes following spinal cord injury.

Spinal cord injuries (SCI) are traumatic events with limited treatment options. Following injury, the lesion site experiences a drastic change to both its structure and vasculature which reduces its ability for tissue regeneration. Despite the lack of clinical options, researchers are investigating therapies to induce neuronal regeneration. Cell-based therapies have long been assessed in the context of SCI to promote neuronal protection and repair. Vascular endothelial growth factor (VEGF) not only demonstrates this ability, but also demonstrates angiogenic potential to promote blood vessel formation. While there have been numerous animal studies investigating VEGF, further research is still warranted to pinpoint its role following SCI. This review aims to discuss the literature surrounding the role of VEGF following SCI and its potential in promoting functional recovery.

Using machine learning to predict 30-day readmission and reoperation following resection of supratentorial high-grade gliomas: an ACS NSQIP study involving 9418 patients.

OBJECTIVE: High-grade gliomas (HGGs) are among the rarest yet most aggressive tumor types in neurosurgical practice. In the current literature, few studies have assessed the drivers of early outcomes following resection of these tumors and investigated their association with quality of care. The authors aimed to identify the clinical predictors for 30-day readmission and reoperation following HGG surgery using the American College of Surgeons (ACS) National Surgical Quality Improvement Project (NSQIP) database and sought to create web-based applications predicting each outcome. METHODS: Using the ACS NSQIP database, the authors conducted a retrospective, multicenter cohort analysis of patients who underwent resection of supratentorial HGGs between January 1, 2016, and December 31, 2020. Demographics and comorbidities were extracted. The primary outcomes were 30-day unplanned readmission and reoperation. A stratified 80:20 split of the available data was carried out. Supervised machine learning algorithms were trained to predict 30-day outcomes. RESULTS: A total of 9418 patients were included in our cohort. The observed rate of unplanned readmission within 30 days of surgery was 13.0% (n = 1221). In terms of predictors, weight, chronic steroid use, preoperative blood urea nitrogen level, and white blood cell count were associated with a higher risk of readmission. The observed rate of unplanned reoperation within 30 days of surgery was 5.2% (n = 489). In terms of predictors, increased weight, longer operative time, and more days between hospital admission and operation were associated with an increased risk of early reoperation. The random forest algorithm showed the highest predictive performance for early readmission (area under the curve [AUC] = 0.967), while the XGBoost algorithm showed the highest predictive performance for early reoperation (AUC = 0.985). Web-based tools for both outcomes were deployed (https://glioma-readmission.herokuapp.com/ and https://glioma-reoperation.herokuapp.com/). CONCLUSIONS: In this study, the authors provide the first nationwide analysis for short-term outcomes in patients undergoing resection of supratentorial HGGs. Multiple patient, hospital, and admission factors were associated with readmission and reoperation, confirmed by machine learning predicting patients' prognosis, leading to better planning preoperatively and subsequently improved personalized patient care.

Surgical management of sacral schwannomas: a 21-year mayo clinic experience and comparative literature analysis.

INTRODUCTION: Sacral and presacral schwannomas are rare, accounting for a minority of spinal schwannomas. We present our institution's experience surgically treating spinal schwannomas and compare it to the literature. METHODS: Data were collected for 27 patients treated surgically for sacral or presacral schwannoma between 1997 and 2018 at all Mayo Clinic locations and 93 patients in the literature. Kaplan-Meier disease-free survival analysis was conducted. Unpaired two-sample t tests and Fisher's exact tests assessed statistical significance between groups. RESULTS: Our patients and those in the literature experienced a similar age at diagnosis (49.9 y/o. vs 43.4 y/o., respectively). Most of our patients (59.3%) reported full recovery from symptoms, while a minority reported partial recovery (33.3%) and no recovery (11.1%). A smaller percentage in the literature experienced full recovery (31.9%) and partial recovery (29.8%) but also no recovery (1.1%). Our patients experienced fewer complications (14.8% versus 25.5%). Disease-free survival curves for all patients showed no significant variation in progression by extent of resection of schwannoma (log-rank P = 0.26). No lesion progression was associated with full or partial symptom improvement (p = 0.044), and female patients were more likely to undergo resection via a posterior approach (p = 0.042). CONCLUSION: Outcomes of patients with sacral or presacral schwannomas vary based on patient demographics, tumor characteristics, symptoms, and surgical treatment. Among the range of symptoms experienced by these patients, the most common is pain. Prognosis improves and overall survival is high when the surgical approach towards sacral schwannomas is prepared and executed appropriately.

Emerging innovations for lumbar spondylolisthesis management: a systematic review of active and prospective clinical trials.

The literature has had some conflicting evidence regarding the effective management of lumbar spondylolisthesis (LS). Herein, we review active and prospective clinical trials to identify the emerging trends for the management of LS. A systematic search was conducted utilizing the NIH Clinical Trials database using the search term "lumbar spondylolisthesis" on February 2, 2022. Currently active and prospective clinical trials for LS were included and analyzed. All statistical analyses were performed on R 4.1.2. We identified 37 clinical trials. Nearly half the trials (n = 18, 48.6%) include novel technologies; 6 (16.2%) are comparing surgical approaches, of which 4 (67%) include decompression alone versus decompression with instrumented fusion; 6 (16.2%) are evaluating perioperative pain management protocols, of which 3 (50%) include bupivacaine or ropivacaine; 3 (8.1%) are evaluating alternative medicines in LS; 2 (5.4%) are observational studies about the natural history of LS; 1 (2.7%) involves surgical infection prophylaxis; and 1 (2.7%) is evaluating AK1320 microspheres. The 18 trials involving novel technologies include 3D-printed titanium cages (n = 3, 16.7%), interbody implants (n = 4, 22.2%), bone graft materials (n = 4, 22.2%), and miscellaneous intraoperative devices (n = 7, 38.9%). The top 3 outcomes measured were Oswestry Disability Index (n = 28, 75.7%), visual analog scale (n = 21, 56.7%), and postoperative radiographs (n = 16, 43.2%). Patient-reported outcome measures (PROMs) were included in 34 (91.9%) trials, while 23 (62.2%) trials included lumbar spine imaging. LS can often require a multifaceted approach. Novel technologies and utilization of PROMs appear to be a significant emerging trend in LS management.

R2 advances in robotic-assisted spine surgery: comparative analysis of options, future directions, and bibliometric analysis of the literature.

Spine surgery has undergone rapid advancements over the past several decades with the emergence of robotic and minimally invasive surgery (MIS). While conventional MIS spine surgery has had relative success, its complication profile has warranted continued efforts to improve clinical outcomes. We discuss the functional, clinical, and financial aspects of four robotic options for spinal pathologies, namely ROSA, Mazor X, Da Vinci, and ExcelsiusGPS, and conduct a bibliometric analysis to better understand current trends and applications of these robots as the field of robotic spine surgery continues to grow. An extensive search of English-language published literature on robotic-assisted spinal surgery was performed in Elsevier's Scopus database. A bibliometric analysis was then performed on the top 100 most cited papers. The search yielded articles regarding robotic-assisted spine surgery application, limitations, and functional outcomes secondary to spine pathology. Accuracy analyses of 1733 screw placements were reviewed. The top 100 papers were published between 1992 and 2020, with a significant increase from 2015 onwards. The top publishing institution was John Hopkins University (n = 8). The top contributing author was Dr. Isador H. Lieberman (n = 6). The USA (n = 34) had the most articles on robotic spinal surgery, followed by Germany (n = 12). This review examines robotic applications in spine surgery, including four available options: ROSA, Mazor X, Da Vinci, and ExcelsiusGPS. Publication output over time, surgical outcomes, screw accuracy, and cost-effectiveness of these technologies have been investigated here. Certain robots have functional, clinical, and financial differences worth noting. Given the dearth of existing literature reporting postoperative complications and long-term comparative outcomes, there is a clear need for further studies on this matter.

Systems neuroimmunology: a review of multiomics methodologies to characterize neuroimmunological interactions in spinal and cranial diseases.

Neuroimmunology plays a critical role in our understanding of the pathophysiological processes that underlie a variety of diseases treated by neurosurgeons, including degenerative disc disease (DDD), glioblastoma (GBM), aneurysmal subarachnoid hemorrhage (aSAH), and others. Compared with traditional methods in neuroimmunology, which study one pathway or gene at a time, emerging multiomics methodologies allow for holistic interrogation of multiple immune-signaling pathways to test hypotheses and the effects of therapeutics at a systems level. In this review, the authors summarize key concepts for gathering and analyzing multiomics data so that neurosurgeons can contribute to the emerging field of systems neuroimmunology. Additionally, they describe 3 use cases, based on original research published by their group and others, that utilize transcriptomic, metabolomic, and proteomic analyses to study immune-signaling pathways in DDD, aSAH, and GBM. Through these use cases, techniques for performing machine learning and network-based analyses to generate new clinical insights from multiomics data are shared. The authors hope that neurosurgeons might use this review as a summary of common tools and principles in systems immunology to better engage in creating the immunotherapies of tomorrow.

Outcomes of Acute Respiratory Failure in Patients With Cancer in the United States.

OBJECTIVE: To determine the epidemiological effect-magnitude and outcomes of patients with cancer vs those without cancer who are hospitalized with acute respiratory failure (ARF). PATIENTS AND METHODS: We reviewed hospitalizations within the National Inpatient Sample (NIS) database between January 1, 2016, and December 31, 2018. Patients were classified based on a diagnosis of solid-organ cancer, hematologic cancer, or no cancer. Noninvasive positive pressure ventilation (NIPPV) failure was defined as patients who initially received NIPPV and had progression to invasive mechanical ventilation. Weighted samples were used to derive population estimates. RESULTS: During the study period, there were an estimated 8,837,209 admissions with ARF in the United States, 8.9% (783,625) of which had solid-organ cancer and 2.0% (176,095) had hematologic cancers. Annually, 319,907 patients with cancer are admitted with ARF, with 27.3% (87,302) requiring invasive mechanical ventilation and 10.0% (31,998) requiring NIPPV. In-hospital mortality was higher in patients with cancer vs those without cancer (24.0% [76,813] vs 12.3% [322,465]; P<.001), and this proprotion persisted when stratified by the highest method of oxygen delivery. Patients with cancer had longer hospital length of stay (7.0 days [3.0 to 12.0 days] vs 5.0 days [3.0 to 10.0 days]; P<.001) and were more likely to have NIPPV failure (14.9% [3,992] vs 12.8% [41,875]). Compared with those with solid-organ cancer, patients with hematologic cancers experienced worse outcomes. The association between underlying cancer diagnosis and outcomes remained consistent when adjusted for age, sex, and comorbidities. CONCLUSION: In the United States, patients with cancer account for over 10% of ARF hospital admissions (959,720 of 8,837,209). They experience an approximately 2-fold higher mortality versus those without cancer. Those with hematologic cancers appear to experience worse outcomes than patients with solid-organ cancers.

High-Value Epilepsy Care in the United States: Predictors of Increased Costs and Complications from the National Inpatient Sample Database 2016-2019.

BACKGROUND: For patients with medically refractory epilepsy, newer minimally invasive techniques such as laser interstitial thermal therapy (LITT) have been developed in recent years. This study aims to characterize trends in the utilization of surgical resection versus LITT to treat medically refractory epilepsy, characterize complications, and understand the cost of this innovative technique to the public. METHODS: The National Inpatient Sample database was queried from 2016 to 2019 for all patients admitted with a diagnosis of medically refractory epilepsy. Patient demographics, hospital length of stay, complications, and costs were tabulated for all patients who underwent LITT or surgical resection within these cohorts. RESULTS: A total of 6019 patients were included, 223 underwent LITT procedures, while 5796 underwent resection. Significant predictors of increased patient charges for both cohorts included diabetes (odds ratio: 1.7, confidence interval [CI]: 1.44-2.19), infection (odds ratio: 5.12, CI 2.73-9.58), and hemorrhage (odds ratio: 2.95, CI 2.04-4.12). Procedures performed at nonteaching hospitals had 1.54 greater odds (CI 1.02-2.33) of resulting in a complication compared to teaching hospitals. Insurance status did significantly differ (P = 0.001) between those receiving LITT (23.3% Medicare; 25.6% Medicaid; 44.4% private insurance; 6.7 Other) and those undergoing resection (35.3% Medicare; 22.5% Medicaid; 34.7% private Insurance; 7.5% other). When adjusting for patient demographics, LITT patients had shorter length of stay (2.3 vs. 8.9 days, P < 0.001), lower complication rate (1.9% vs. 3.1%, P = 0.385), and lower mean hospital ($139,412.79 vs. $233,120.99, P < 0.001) and patient ($55,394.34 vs. $37,756.66, P < 0.001) costs. CONCLUSIONS: The present study highlights LITT's advantages through its association with lower costs and shorter length of stay. The present study also highlights the associated predictors of LITT versus resection, such as that most LITT cases happen at academic centers for patients with private insurance. As the adoption of LITT continues, more data will become available to further understand these issues.

Trends in the Utilization of Surgical Modalities for the Treatment of Drug-Resistant Epilepsy: A Comprehensive 10-Year Analysis Using the National Inpatient Sample.

BACKGROUND AND OBJECTIVES: Epilepsy is considered one of the most prevalent and severe chronic neurological disorders worldwide. Our study aims to analyze the national trends in different treatment modalities for individuals with drug-resistant epilepsy and investigate the outcomes associated with these procedural trends in the United States. METHODS: Using the National Inpatient Sample database from 2010 to 2020, patients with drug-resistant focal epilepsy who underwent laser interstitial thermal therapy (LITT), open surgical resection, vagus nerve stimulation (VNS), or responsive neurostimulation (RNS) were identified. Trend analysis was performed using piecewise joinpoint regression. Propensity score matching was used to compare outcomes between 10 years prepandemic before 2020 and the first peak of the COVID-19 pandemic. RESULTS: This study analyzed a total of 33 969 patients with a diagnosis of drug-resistant epilepsy, with 3343 patients receiving surgical resection (78%), VNS (8.21%), RNS (8%), and LITT (6%). Between 2010 and 2020, there was an increase in the use of invasive electroencephalography monitoring for seizure zone localization (P = .003). There was an increase in the use of LITT and RNS (P < .001), while the use of surgical resection and VNS decreased over time (P < .001). Most of these patients (89%) were treated during the pre-COVID pandemic era (2010-2019), while a minority (11%) underwent treatment during the COVID pandemic (2020). After propensity score matching, the rate of pulmonary complications, postprocedural hematoma formation, and mortality were slightly higher during the pandemic compared with the prepandemic period (P = .045, P = .033, and P = .026, respectively). CONCLUSION: This study indicates a relative decrease in the use of surgical resections, as a treatment for drug-resistant focal epilepsy. By contrast, newer, minimally invasive surgical approaches including LITT and RNS showed gradual increases in usage.

Utilizing pre- and postoperative radiological parameters to predict surgical outcomes following untethering for tethered cord syndrome in a pediatric population.

OBJECTIVE: Tethered cord syndrome (TCS) can lead to significant downstream neurological deficits including gait deterioration, incontinence, and often unexplained chronic low-back pain. Surgical intervention may relieve symptoms, but there are no defined radiological parameters associated with surgical outcomes and functional status. The authors aimed to define pre- and postoperative radiological parameters for assessing surgical outcomes in TCS. METHODS: The authors performed a single-center retrospective review of all pediatric patients treated for TCS between 2016 and 2021. Patient baseline characteristics and operative metrics included age, sex, level of conus, level of procedure, tethering pathology, symptoms at presentation, complications, improvement of symptoms, and reoperation rate. MRI measurements included pre- and postoperative anterior canal distance (ACD) and bending angle (BA). RESULTS: Thirty-three pediatric patients were identified who underwent untethering of the spinal cord and had pre- and postoperative MRI between 2016 and 2021. The mean patient age was 5.64 ± 5.33 years. Twenty patients (60.60%) were female. Regarding the site of untethering, 31 procedures (93.93%) were performed at the lumbosacral region and 2 (6.06%) were performed at the thoracolumbar region. The conus medullaris was found above L3 in 21.21% of patients. Postoperatively, 18.18% of patients experienced complications, 48.48% showed improvement in their symptoms, and 48.48% were equivocal or had persistent symptoms. The mean preoperative ACD0 (measured from the posterior vertebral body margin [middle] to the anterior margin of the conus medullaris) was 6.15 ± 3.18 mm, the postoperative ACD0 was 2.25 ± 2.72 mm, and the average change in ACD0 was -0.90 ± 1.31 mm. The mean preoperative BA was 26.00° ± 11.56°, the mean postoperative BA was 15.92° ± 9.81°, and the average change in BA was -10.08° ± 8.80°. An optimal cutoff value for preoperative BA to predict reoperation in pediatric patients with complex TCS undergoing surgery was ≥ 31.70° (area under the curve = 0.83). CONCLUSIONS: In surgically treated patients with TCS, certain preoperative radiological parameters may be important in predicting postoperative surgical outcomes; these parameters can be evaluated and reported to indicate patients at high risk for complications. Further prospective multicenter research is warranted to offer robust evidence of association of patient outcomes with preoperative radiological parameters in TCS.

Deep Learning Approaches for Glioblastoma Prognosis in Resource-Limited Settings: A Study Using Basic Patient Demographic, Clinical, and Surgical Inputs.

BACKGROUND: Glioblastoma (GBM) is the most common brain tumor in the United States, with an annual incidence rate of 3.21 per 100,000. It is the most aggressive type of diffuse glioma and has a median survival of months after treatment. This study aims to assess the accuracy of different novel deep learning models trained on a set of simple clinical, demographic, and surgical variables to assist in clinical practice, even in areas with constrained health care infrastructure. METHODS: Our study included 37,095 patients with GBM from the SEER (Surveillance Epidemiology and End Results) database. All predictors were based on demographic, clinicopathologic, and treatment information of the cases. Our outcomes of interest were months of survival and vital status. Concordance index (C-index) and integrated Brier scores (IBS) were used to evaluate the performance of the models. RESULTS: The patient characteristics and the statistical analyses were consistent with the epidemiologic literature. The models C-index and IBS ranged from 0.6743 to 0.6918 and from 0.0934 to 0.1034, respectively. Probabilistic matrix factorization (0.6918), multitask logistic regression (0.6916), and logistic hazard (0.6916) had the highest C-index scores. The models with the lowest IBS were the probabilistic matrix factorization (0.0934), multitask logistic regression (0.0935), and logistic hazard (0.0936). These models had an accuracy (1-IBS) of 90.66%; 90.65%, and 90.64%, respectively. The deep learning algorithms were deployed on an interactive Web-based tool for practical use available via https://glioblastoma-survanalysis.herokuapp.com/. CONCLUSIONS: Novel deep learning algorithms can better predict GBM prognosis than do baseline methods and can lead to more personalized patient care regardless of extensive electronic health record availability.

Alginate hydrogels: A potential tissue engineering intervention for intervertebral disc degeneration.

Intervertebral disc (IVD) degeneration is a major cause of low back pain and disability, affecting millions of people worldwide. Current treatments for IVD degeneration are limited to invasive surgery or pain management. Recently, there has been increasing interest in the use of biomaterials, such as alginate hydrogels, for the treatment of IVD degeneration. Alginate hydrogels are an example of such a biomaterial that is biocompatible and can be tailored to mimic the native extracellular matrix of the IVD. Derived from alginate, a naturally derived polysaccharide from brown seaweed that can be transformed into a gelatinous solution, alginate hydrogels are emerging in the field of tissue engineering. They can be used to deliver therapeutic agents, such as growth factors or cells, to the site of injury, providing a localized and sustained release that may enhance treatment outcomes. This paper provides an overview on the use of alginate hydrogels for the treatment of IVD degeneration. We discuss the properties of alginate hydrogels and their potential applications for IVD regeneration, including the mechanism against IVD degeneration. We also highlight the research outcomes to date along with the challenges and limitations of using alginate hydrogels for IVD regeneration, including their mechanical properties, biocompatibility, and surgical compatibility. Overall, this review paper aims to provide a comprehensive overview of the current research on alginate hydrogels for IVD degeneration and to identify future directions for research in this area.

Single-Level Anterior Lumbar Interbody Fusion versus Minimally Invasive Transforaminal Lumbar Interbody Fusion at L5/S1 for an Obese Population.

STUDY DESIGN: Retrospective study. PURPOSE: To compare perioperative outcomes, patient-reported outcome measures (PROMs), and minimal clinically important difference (MCID) achievement rates for an obese patient cohort between single-level minimally invasive (MIS) transforaminal lumbar interbody fusion (TLIF) vs. anterior lumbar interbody fusion (ALIF). OVERVIEW OF LITERATURE: To the best of our knowledge, no study has compared the outcomes of MIS TLIF and ALIF in an obese population. METHODS: Obese patients (body mass index [BMI] ≥30.0 kg/m2) who underwent single-level MIS TLIF or ALIF at L5/S1 were included in the study. Demographic/perioperative variables, presenting patient pathology, and 1-year arthrodesis statistics were collected. PROM scores for Visual Analog Scale (VAS) back/leg, Oswestry Disability Index, 12-item Short Form Physical Composite Scale, and Patient-Reported Outcome Measurement Information System Physical Function (PROMIS-PF) were collected from preoperative and postoperative (6 weeks, 12 weeks, 6 months, 1 year, 2 years) PROMIS-PF. The obese patients were classified based on the procedure they underwent (MIS TLIF vs. ALIF). RESULTS: The criteria were met by 210 patients in total. After coarsened exact matching for Charlson comorbidity index score, degenerative spondylolisthesis, isthmic spondylolisthesis, degenerative scoliosis, foraminal stenosis, insurance, male, and ethnicity, 94 obese patients were included in the total cohort, with 59 receiving MIS TLIF and 35 receiving ALIF. ALIF recipients had higher PROMIS-PF scores at 6 weeks (p=0.014) and 12 weeks (p=0.030), as well as a higher VAS leg at 2 years (p=0.017). Following multiple regression accounting for differences in baseline BMI, only the 6-week PROMIS-PF significantly differed (p=0.028), with no other intergroup differences in mean PROMs between fusion types. Aside from a significantly higher 6-week MCID achievement rate for PROMIS-PF among ALIF recipients (p=0.006), no differences in attainment were observed. CONCLUSIONS: There were no statistically significant differences in perioperative characteristics, fusion rates, PROMs, or MCID achievement between obese patients receiving MIS TLIF vs. ALIF. As a result, our findings indicate that MIS TLIF and ALIF at L5/S1 are equally effective in an obese patient population.

The Virtual Vision of Neurosurgery: How Augmented Reality and Virtual Reality are Transforming the Neurosurgical Operating Room.

BACKGROUND: In this era of imagination and technological innovation, mixed reality systems such as virtual reality (VR) and augmented reality (AR) are contributing to a wide array of neurosurgical care, from the betterment of surgical planning and surgical comfort to novel treatments and improved resident education. These systems can augment procedures that require high-level dexterity such as minimally invasive surgery and tumor excisions, as well as peripheral and neurovascular surgery. We define and compare the technological features, indications, and characterized outcomes of VR and AR systems in the context of neurosurgery through a review of the literature to date. Moreover, this review discusses the limitations of VR and AR and includes an overview of the cost-effectiveness of each of these systems. METHODS: An extensive review of the literature on AR and VR was performed using PubMed, OVID Medline, and Embase from January 1, 2006 to April 2, 2022. Terms used for the search included AR, spinal surgery, VR, and neurosurgery. RESULTS: The search yielded full-text English language-related articles regarding VR and AR application, limitations, and functional outcomes in neurosurgery. An initial set of 121 studies were screened and reviewed for content. Thirteen studies were included, which involved 162 patients, 550 screw placements, 58 phantom spines, and learning points from simulation training of 276 involved residents. CONCLUSIONS: This literature review examines recent research into VR and AR applications in neurosurgical care. The literature establishes that there are technological features, indications, outcomes, limitations, and cost-effectiveness differences between these systems. Based on ongoing and evolving applications of the VR and AR systems, the innovative potential that they make available to the future of neurosurgical patient care makes clear the need for further studies to understand the nuances between their differing technological advances.