Bhandarkar, Archis R.

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.

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.

OBJECTIVE At present, females constitute less than 10% of neurosurgeons in the US, despite representing approximately half of all medical students. Multiple barriers have been described for females entering the neurosurgical field, particularly academic neurosurgery. Understanding the environment that female neurosurgeons face and any potential barriers preventing career advancement is needed to recruit, promote, and retain females in neurosurgery. METHODS The gender composition of editorial boards for 5 high-impact neurosurgery journals was analyzed from 2000 to 2020. The names of editorial board members were obtained directly from the journal administration, physical copies of the published journal, or publicly available data through each journal’s website. The gender, degrees, academic titles, H-index, and country were determined for each individual and statistical tests were performed to identify significant differences. RESULTS Of the 466 identified individuals that served on at least one editorial board between 2000 and 2020, there were 36 females (7.7%) and 430 males (92.3%). There were no significant differences between males and females serving on multiple editorial boards. Most females possessed an additional graduate degree (58.3%), while only one-third of males (33.5%) obtained such a degree (p = 0.002). In addition, males had significantly higher average H-indices than females (p = 0.002). These trends were also observed when analyzing only US-based editorial board members. Although females were more likely overall to be identified as associate professors, males were more likely to be appointed as full professors (p = 0.001); this trend did not remain true in the US-based cohort. When analyzing the editorial boards for individual journals, all 5 journals experienced an increase of female representation since 2000 or since their inception after 2000. The highest proportion of females for a single journal was 27.3% in 2020. All other journals ranged from 11.0% to 13.5% in 2020. CONCLUSIONS When entering the field of neurosurgery, females continue to face significant social and academic barriers. While the proportion of females on editorial boards for neurosurgery journals in 2020 is consistent with the proportion of practicing female neurosurgeons, there is a statistically significantly higher likelihood that females possess additional graduate degrees and lower H-indices compared to their male counterparts. The authors encourage neurosurgical journals to continue expanding female representation on editorial boards.

The authors describe an endoscopic strip craniectomy through a single incision for the treatment of sagittal craniosynostosis in a young infant. The endoscopic strip craniectomy was first introduced with the use of two incisions on either end of the fused suture. This single-incision technique offers several advantages. There is a cosmetic advantage and a reduced risk of wound complications. This technique also allows for early control of emissary veins and an inside-out identification of the lambdoid sutures. Endoscopic visualization is optimized to reduce the risk of blood loss, especially because circulating blood volume is very limited in these young infants. The video can be found here: https://vimeo.com/514366415

OBJECTIVE Metric tracking of grant funding over time for academic neurosurgeons sorted by gender informs the current climate of career development internationally for women in neurosurgery. METHODS Multivariate linear trend analysis of grant funding awarded to neurosurgeons in the NIH and World Research Portfolio Online Reporting Tools Expenditures and Results (RePORTER) was performed. Traveling fellowships for international neurosurgery residents sponsored by the AANS and Congress of Neurological Surgeons (CNS) were also analyzed. RESULTS Within the US, funding awarded to female neurosurgeons has remained static from 2009 to 2019 after adjusting for inflation and overall trends in NIH funding (β = −$0.3 million per year, p = 0.16). Internationally, female neurosurgeons represented 21.7% (n = 5) of project leads for World RePORTER grants. Traveling fellowships are also an important building block for young international female neurosurgeons, of which 7.4% (n = 2) of AANS international traveling fellowships and 19.4% (n = 7) of AANS/CNS pediatrics international traveling fellowships are women. CONCLUSIONS Over the past decade, funding has increased in neurosurgery without a concordant increase in funding awarded to women. Recognition of this trend is essential to focus efforts on research and career development opportunities for women in neurosurgery. Worldwide, female neurosurgeons head one-fifth of the funded project leads and constitute a minority of international traveling fellowships awarded by organized neurosurgery.

Oncolytic viruses (OVs) are a class of immunotherapeutic agents with promising preclinical results for the treatment of glioblastoma (GBM) but have shown limited success in recent clinical trials. Advanced bioengineering principles from disciplines such as synthetic and systems biology are needed to overcome the current challenges faced in developing effective OV-based immunotherapies for GBMs, including off-target effects and poor clinical responses. Synthetic biology is an emerging field that focuses on the development of synthetic DNA constructs that encode networks of genes and proteins (synthetic genetic circuits) to perform novel functions, whereas systems biology is an analytical framework that enables the study of complex interactions between host pathways and these synthetic genetic circuits. In this review, the authors summarize synthetic and systems biology concepts for developing programmable, logic-based OVs to treat GBMs. Programmable OVs can increase selectivity for tumor cells and enhance the local immunological response using synthetic genetic circuits. The authors discuss key principles for developing programmable OV-based immunotherapies, including how to 1) select an appropriate chassis, a vector that carries a synthetic genetic circuit, and 2) design a synthetic genetic circuit that can be programmed to sense key signals in the GBM microenvironment and trigger release of a therapeutic payload. To illustrate these principles, some original laboratory data are included, highlighting the need for systems biology studies, as well as some preliminary network analyses in preparation for synthetic biology applications. Examples from the literature of state-of-the-art synthetic genetic circuits that can be packaged into leading candidate OV chassis are also surveyed and discussed.