Precision oncology in neurofibromatosis type 1: quantification of differential sensitivity to selumetinib in plexiform neurofibromas using single-cell RNA sequencing.

PURPOSE: Selumetinib is an FDA-approved targeted therapy for plexiform neurofibromas in neurofibromatosis type 1(NF1) with durable response rates seen in most, but not all patients. In this proof-of-concept study, we demonstrate single-cell RNA sequencing(scRNAseq) as a technique for quantifying drug response to selumetinib at the single cell level. METHODS: scRNAseq data from neurofibroma biopsies was obtained from a public genomics repository. Schwann cell populations were identified through standard clustering techniques and single-cell selumetinib sensitivity was quantified on a scale of 0(resistant) to 1(sensitive) based on the expression pattern of a 500 gene selumetinib sensitivity signature from the BeyondCell sensitivity library. RESULTS: A total of seven plexiform neurofibromas were included in our final analysis. The median absolute number of Schwann cells across samples was 658 cells (IQR: 1,029 cells, Q1-Q3: 135 cells to 1,163 cells). There was a statistically significant difference in selumetinib sensitivity profiles across samples (p < 0.001). The tumor with the highest median selumetinib sensitivity score had a median selumetinib sensitivity score of 0.64(IQR: 0.14, Q1-Q3: 0.59-0.70, n = 112 cells) and the tumor with the lowest median selumetinib sensitivity score had a median score of 0.37 (IQR: 0.21, Q1-Q3: 0.27-0.48, n = 1,034 cells). CONCLUSIONS: scRNAseq of plexiform neurofibroma biopsies reveals differential susceptibilities to selumetinib on a single cell level. These findings may explain the partial responses seen in clinical trials of selumetinib for NF1 and demonstrate the value of collecting scRNAseq data for future NF1 trials.

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.

An Integrated Voice Recognition and Natural Language Processing Platform to Automatically Extract Thoracolumbar Injury Classification Score Features From Radiology Reports.

BACKGROUND: Many predictive models for estimating clinical outcomes after spine surgery have been reported in the literature. However, implementation of predictive scores in practice is limited by the time-intensive nature of manually abstracting relevant predictors. In this study, we designed natural language processing (NLP) algorithms to automate data abstraction for the thoracolumbar injury classification score (TLICS). METHODS: We retrieved the radiology reports of all Mayo Clinic patients with an International Classification of Diseases, 9th or 10th revision, code corresponding to a fracture of the thoracolumbar spine between January 2005 and October 2020. Annotated data were used to train an N-gram NLP model using machine learning methods, including random forest, stepwise linear discriminant analysis, k-nearest neighbors, and penalized logistic regression models. RESULTS: A total of 1085 spine radiology reports were included in our analysis. Our dataset included 483 compression, 401 burst, 103 translational/rotational, and 98 distraction fractures. A total of 103 reports had documented an injury of the posterior ligamentous complex. The overall accuracy of the random forest model for fracture morphology feature detection was 76.96% versus 65.90% in the stepwise linear discriminant analysis, 50.69% in the k-nearest neighbors, and 62.67% in the penalized logistic regression. The overall accuracy to detect posterior ligamentous complex integrity was highest in the random forest model at 83.41%. Our random forest model was implemented in the backend of a web application in which users can dictate reports and have TLICS features automatically extracted. CONCLUSIONS: We have developed a machine learning NLP model for extracting TLICS features from radiology reports, which we deployed in a web application that can be integrated into clinical practice.

Characterizing T-cell dysfunction and exclusion signatures in malignant peripheral nerve sheath tumors reveals susceptibilities to immunotherapy.

PURPOSE: Malignant peripheral nerve sheath tumors (MPNSTs) are malignant tumors that arise from peripheral nerves and are the leading cause of mortality in Neurofibromatosis Type 1 (NF1). In this study, we characterized whether transcriptomic signatures of T-cell dysfunction (TCD) and exclusion (TCE) that inversely correlate with response to immune checkpoint blockade (ICB) immunotherapy exist in MPNSTs. METHODS: MPNST transcriptomes were pooled from Gene Expression Omnibus (GEO). For each sample, a tumor immune dysfunction and exclusion (TIDE) score, TCD and TCE subscores, and cytotoxic T-cell(CTL) level were calculated. In the TIDE predictive algorithm, tumors are predicted to have an ICB response if they are either immunologically hot (CTL-high) without TCD or immunologically cold (CTL-low) without TCE. TIDE scores greater than zero correspond with ICB nonresponse. RESULTS: 73 MPNST samples met inclusion criteria, including 50 NF1-associated MPNSTs (68.5%). The average TIDE score was + 0.41 (SD = 1.16) with 22 (30.1%) predicted ICB responders. 11 samples were CTL-high (15.1%) with an average TCD score of + 0.99 (SD = 0.63). Among 62 CTL-low tumors, 21 were predicted to have ICB response with an average TCE score of + 0.31(SD = 1.20). Age(p = 0.18), sex(p = 0.41), NF1 diagnosis (p = 0.17), and PRC2 loss(p = 0.29) were not associated with ICB responder status. CONCLUSIONS: Transcriptomic analysis of TCD and TCE signatures in MPNST samples reveals that a select subset of patients with MPNSTs may benefit from ICB immunotherapy.

Bariatric surgery reduces odds of perioperative complications after inpatient hysterectomy: Analysis from a national database, 2016 to 2018.

BACKGROUND: Increased body mass index is a known risk factor for increased adverse events post-hysterectomy. The effects of previous bariatric surgery on outcomes after inpatient hysterectomy are not well elucidated. METHODS: The 2016 to 2018 National Inpatient Sample was queried for patients who underwent hysterectomy using International Classification of Disease 10 Procedure Codes before a matched analysis was performed to neutralize the potential confounding effects of comorbidities, body mass index, and age. Patients were divided into the following 2 groups: a case group (those with a history of bariatric surgery) and a control group (those without a history of bariatric surgery). Patients in the respective groups were matched 1:2 by age, Elixhauser comorbidity score, and body mass index at the time of surgery to analyze the risk of complications and mean length of stay. RESULTS: When 1:2 case-control matching was performed, women with a history of bariatric surgery (N = 595) had significantly fewer complications and decreased mean length of stay than the non-bariatric group (N = 1,190), even after controlling for body mass index at the time of hysterectomy. CONCLUSIONS: When matched for age, body mass index, and comorbidity score, patients with previous bariatric surgery had fewer complications and shorter lengths of stay than patients without a history of bariatric surgery. Women with a body mass index ≥40 kg/m2 requiring non-urgent hysterectomy may benefit from undergoing bariatric surgery first.

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.

Microfluidic 'brain-on chip' systems to supplement neurological practice: development, applications and considerations.

Among the greatest general challenges in bioengineering is to mimic human physiology. Advanced efforts in tissue engineering have led to sophisticated 'brain-on-chip' (BoC) microfluidic devices that can mimic structural and functional aspects of brain tissue. BoC may be used to understand the biochemical pathways of neurolgical pathologies and assess promising therapeutic agents for facilitating regenerative medicine. We evaluated the potential of microfluidic BoC devices in various neurological pathologies, such as Alzheimer's, glioblastoma, traumatic brain injury, stroke and epilepsy. We also discuss the principles, limitations and future considerations of BoC technology. Results suggest that BoC models can help understand complex neurological pathologies and augment drug testing efforts for regenerative applications. However, implementing organ-on-chip technology to clinical practice has some practical limitations that warrant greater attention to improve large-scale applicability. Nevertheless, they remain to be versatile and powerful tools that can broaden our understanding of pathophysiological and therapeutic uncertainties to neurological diseases.

In this paper, the authors describe the role of microfluidic 'brain-on-chip' systems as a tool to model and study the human brain. While animal studies have provided significant insights, they lack the complexity of human brain tissue in order to verify the effects of drugs on patients, study complex physiological pathways or personalize regenerative therapies. This makes studying diseases of complex human organs challenging. Microfluidics is a field of study that can address these challenges by developing sophisticated and miniaturized devices that can chamber human tissue. These devices could allow scientists to better study diseases on a model that is accurate and controllable, allowing researchers to better understand complex diseases, assess drug efficacy to specific areas of the brain and potentially accelerate the development of new therapies. Herein, we characterize the principles, development and challenges of microfluidics and the role they have served in different neurological diseases.

The association between bone mineral density and proximal junctional kyphosis in adult spinal deformity: a systematic review and meta-analysis.

OBJECTIVE: Proximal junctional kyphosis (PJK) is a complication of surgical management for adult spinal deformity (ASD) with a multifactorial etiology. Many risk factors are controversial, and their relative importance is not fully understood. The authors aimed to elucidate the association between bone mineral density (BMD) and PJK. METHODS: A systematic literature search was performed using PubMed and Web of Science keywords of "Proximal Junctional Kyphosis [MeSH] OR Proximal Junctional Failure [MeSH]" AND "Bone Mineral Density [MeSH] OR Hounsfield Units [MeSH] OR DEXA [MeSH]" set to the date range of January 2002 to July 2022. Studies required a minimum of 10 patients and 12 months of follow-up. Articles were included if they were in the English language and presented a primary retrospective cohort that included a comparison of patients with and without PJK, as well as a radiographic biomarker for BMD, such as Hounsfield units (HU) or T-score. RESULTS: A total of 18 unique studies with 2185 patients who underwent ASD surgery were identified. Of these, 537 patients (24.6%) developed PJK. Eight studies provided T-scores that were amenable to comparison, which found that patients who developed PJK were found to have lower BMD T-scores by a mean of -0.69 (95% CI -0.88 to -0.50; I2 = 63.9%, p < 0.001). The HU at the UIV among patients with the PJK group (n = 101) compared with the non-PJK group (n = 156) was found to be significantly lower (mean difference -32.35, 95% CI -46.05 to -18.65; I2 = 28.7%, p < 0.001). CONCLUSIONS: This meta-analysis suggests that low preoperative BMD as measured by T-score and a diagnosis of osteoporosis were associated with higher postoperative PJK. Additionally, lower HU on CT at the UIV were found to be significant risk factors for postoperative PJK as well. These findings suggest that more attention to preoperative BMD is a risk factor for PJK among ASD patients is warranted.

Peritumoral edema in meningiomas: pathophysiology, predictors, and principles for treatment.

Meningiomas is a tumor of the meninges and is among the most common intracranial neoplasms in adults, accounting for over a third of all primary brain tumors in the United States. Meningiomas can be associated with peritumoral brain edema (PTBE) which if not managed appropriately can lead to poor clinical outcomes. In this review, we summarize the relevant pathophysiology, predictors, and principles for treatment of PTBE. The results of various case-reports and case-series have found that meningioma-associated PTBE have patterns in age, tumor size, and hormone receptor positivity. Our study describes how increased age, increased tumor size, tumor location in the middle fossa, and positive expression of hormone receptors, VEGF, and MMP-9 can all be predictors for worse clinical outcomes. We also characterize treatment options for PTBE such as glucocorticoids and VEGF inhibitors along with the ongoing clinical trials attempting to alleviate PTBE in meningioma cases. The trends summarized in this review can be used to better predict the behavior of meningioma-associated PTBE and establish prognosis models to identify at risk patients.

The LazyBox Educational Intervention Trial: Can Longitudinal Practice on a Low-Fidelity Microsurgery Simulator Improve Microsurgical Skills?

Introduction Every surgical trainee must acquire microsurgical skills within a limited timeframe. Therefore, identifying effective educational strategies to help learners attain these skills is crucial. Objective Establish the effectiveness of a low-fidelity microsurgery simulator to improve the execution and one's perception of the difficulty of basic surgical techniques. Methods From 2021 to 2022, 24 medical students were randomized to either (1) a treatment group (n=12) that engaged in longitudinal practice on a low-fidelity microsurgery simulator (the LazyBox) or (2) a control group (n=12) that did not practice. Students performed vessel loop ligation, catheter macroanastomosis, and synthetic vessel microanastomosis prior to and six weeks after intervention. Both objective metrics and subjective metrics (Swedish Occupational Fatigue Inventory (SOFI) and Surgery Task Load Index (SURG-TLX)) were obtained. Results The treatment and control arms had 1.2 (SD = 2.6) and 2.1 (SD = 2.4) points increase in the vessel loop ligation, respectively (p = 0.39). The treatment and control arms had a 3.4 (SD = 4.1) and 2.9 (SD = 3.6) points increase in the macroanastomosis task, respectively (p = 0.74). In the synthetic vessel microanastomosis task training, the experimental and control arms showed a 5.4 (SD = 8.3) and a 2.9 (SD = 5.6) points increase, respectively (p = 0.30). No differences were found between the groups regarding survey metrics of mental (p = 0.82), temporal (p = 0.23), and physical demands (p = 0.48). Conclusion In our randomized educational intervention, we found no significant difference in objective and subjective metrics of microsurgical task performance between learners who did and did not use the LazyBox simulator.

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.

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.

The role of bevacizumab for treatment-refractory intracranial meningiomas: a single institution's experience and a systematic review of the literature.

INTRODUCTION: Meningiomas account for over 30% of all primary brain tumors. While surgery can be curative for these tumors, several factors may lead to a higher likelihood of recurrence. For recurrent meningiomas, bevacizumab may be considered as a therapeutic agent, but literature regarding its efficacy is sparse. Thus, we present a systematic review of the literature and case series of patients from our institution with treatment-refractory meningiomas who received bevacizumab. METHODS: Patients at our institution who were diagnosed with recurrent meningioma between January 2000 and September 2020 and received bevacizumab monotherapy were included in this study. Bevacizumab duration and dosages were noted, as well as progression-free survival (PFS) after the first bevacizumab injection. A systematic review of the literature was also performed. RESULTS: Twenty-three patients at our institution with a median age of 55 years at initial diagnosis qualified for this study. When bevacizumab was administered, 2 patients had WHO grade I meningiomas, 10 patients had WHO grade II meningiomas, and 11 patients had WHO grade III meningiomas. Median PFS after the first bevacizumab injection was 7 months. Progression-free survival rate at 6 months was 57%. Two patients stopped bevacizumab due to hypertension and aphasia. Systematic review of the literature showed limited ability for bevacizumab to control tumor growth. CONCLUSION: Bevacizumab is administered to patients with treatment-refractory meningiomas and, though its effectiveness is limited, outperforms other systemic therapies reported in the literature. Further studies are required to identify a successful patient profile for utilization of bevacizumab.

Outcomes and Principles of Patient Selection for Laser Interstitial Thermal Therapy for Metastatic Brain Tumor Management: A Multisite Institutional Case Series.

BACKGROUND: Laser interstitial thermal therapy (LITT) is an emerging treatment modality for both primary brain tumors and metastases. We report initial outcomes after LITT for metastatic brain tumors across 3 sites at our institution and discuss potential strategies for optimal patient selection and outcomes. METHODS: International Classification of Diseases, Ninth Revision and Tenth Revision codes were used to identify patients with malignant brain tumors treated via LITT across all 3 Mayo Clinic sites with at least 6 months follow-up. Local control was based on radiologic and clinical evidence. Overall survival was measured from time of receiving LITT until death or end of the study period. RESULTS: Twenty-three patients were treated for progression of a single (n = 21) or multiple (n = 2) previously radiated metastatic lesions and/or radiation necrosis. Median age was 56 years (interquartile range, 47-66.5 years). LITT achieved local control of the lesion in most patients with metastatic tumors or radiation necrosis (n = 18; 81.8%) for the duration of follow-up. One patient did not have local control data available. Thirteen (56.5%) patients remained alive at the end of the study period. No other patients died of their treated disease during the study period; 5 of 10 deaths were attributable to central nervous system progression outside the treated lesion. Although median survival for this cohort has not yet been reached, the current median survival is 16 months (interquartile range, 12-48.5 months) after LITT for metastatic/radiation necrosis lesions. CONCLUSIONS: LITT was associated with sustained local control in 81.8% of patients treated for radiographic progression of metastatic central nervous system disease.

Rate of C8 Radiculopathy in Patients Undergoing Cervicothoracic Osteotomy: A Systematic Appraisal of the Literature.

BACKGROUND: The emergence of C8 radiculopathy is a known complication following cervicothoracic osteotomies. However, the clinical profile of C8 radiculopathy is not well understood. The aim of this study was to investigate the rate of C8 radiculopathy after cervicothoracic osteotomies and to form a clinical profile describing the characteristics through a systematic review of the literature. METHODS: An electronic database search for full-text English articles was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The search yielded results on indications for cervicothoracic osteotomies, surgical approaches, mean follow-up time, and significant complications, including C8 radiculopathy. RESULTS: Our literature search yielded 2135 articles, of which 12 qualified to be included in the analysis. The 12 articles comprised 451 patients undergoing various osteotomy approaches. The mean age of subjects was 51.0 years (range, 11.4-63.2 years), and the majority of patients were male (66%, n = 298). Ankylosing spondylitis was the most frequent indication for surgery (44.8%, n = 202). The number of patients with postoperative C8 radiculopathy was found to decrease over time (1997-2020) by showing statistical significance (r = -0.65, P = 0.021). CONCLUSIONS: Of the 451 patients included in this study, 53 had C8 radiculopathy (11.8% of the total patient population). Moreover, the rate of C8 radiculopathy decreased over time in a statistically significant manner. An understanding of the factors associated with the incidence of C8 radiculopathy is essential for future improvement of patient outcomes.

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.

Transcatheter aortic valve replacement outcomes in solid organ transplant recipients.

BACKGROUND AND AIMS: Transcatheter aortic valve replacement (TAVR) has become the primary treatment for severe symptomatic aortic stenosis in patients >65 years with volumes exceeding surgical aortic valve replacements (SAVR) since 2019. As a less invasive procedure with lower complication rates, TAVR is preferable in most patient populations, particularly those with increased surgical risk. One such population is patients who have undergone solid organ transplant (SOT). We aimed to evaluate periprocedural outcomes and complication rates following TAVR in SOT recipients as compared to the general TAVR population. METHODS: The 2016-2018 National Inpatient Sample (NIS) was queried by ICD-10 PCS codes to identify TAVR cases; hospitalizations were subsequently stratified by SOT history. Multivariate analyses were completed to evaluate complication rates, length of stay (LOS), and cost of stay (COS). RESULTS: No significant difference was observed in mortality rates or post-procedural complications between SOT recipients (n = 223) and those without transplant history undergoing TAVR (n = 29,448) except for increased thromboembolic events captured in transplant patients (p < .001). There was no significant variation in LOS or COS between the two populations; female sex and Black or Hispanic race were predictors of increased inpatient time. CONCLUSIONS: SOT recipients have no increased risk of mortality or periprocedural complications when undergoing TAVR. Though the rate of thromboembolic events was higher in SOT recipients, observation size was small (n = 27 TAVR, n = 4 TAVR + SOT) thus external validity is limited. Based on these data, transplant recipients experience no difference in outcomes following TAVR as compared to patients without a history of organ transplant.

Hybrid surgery: a comparison of early postoperative outcomes between anterior cervical discectomy and fusion and cervical disc arthroplasty.

OBJECTIVE: Hybrid surgery (HS) is the combination of anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA) at different levels in the same operation. The aim of this study was to investigate perioperative variables, 30-day postoperative outcomes, and complications of HS in comparison with those of CDA and ACDF. METHODS: The authors queried the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) registry for patients who underwent multilevel primary HS, CDA, and ACDF for degenerative disc disease from 2015 to 2019. The authors compared these three operations in terms of 30-day postoperative outcomes, specifically readmission and reoperation rates, discharge destination, and complications. RESULTS: This analysis included 439 patients who underwent HS, 976 patients who underwent CDA, and 27,460 patients who underwent ACDF. Patients in the HS and CDA groups were younger, had fewer comorbidities, and myelopathy was less often the indication for surgery compared with patients who underwent ACDF. For the HS group, the unplanned readmission rate was 0.7%, index surgery-related reoperation rate was 0.3%, and nonroutine discharge rate was 2.1%. Major and minor complications were also rare, with rates of 0.2% for each. The mean length of stay in the HS group was 1.5 days. The association of HS with better outcomes in univariate analysis was not evident after adjustment for confounding factors. CONCLUSIONS: The authors found that HS was noninferior to ACDF and CDA in terms of early postoperative outcomes among patients treated for degenerative disc disease.