Magnetic Resonance Imaging-Guided Frameless Stereotactic Injections of the Bilateral Cerebellar Dentate Nuclei in Nonhuman Primates: Technical Note.

BACKGROUND AND OBJECTIVES: Nonhuman primates (NHPs) are important preclinical models for evaluating therapeutics because of their anatomophysiological similarities to humans, and can be especially useful for testing new delivery targets. With the growing promise of cell and gene therapies for the treatment of neurological diseases, it is important to ensure the accurate and safe delivery of these agents to target structures in the brain. However, a standard guideline or method has not been developed for stereotactic targeting in NHPs. In this article, we describe the safe use of a magnetic resonance imaging-guided frameless stereotactic system to target bilateral cerebellar dentate nuclei for accurate, real-time delivery of viral vector in NHPs. METHODS: Seventeen rhesus macaques (Macaca mulatta) underwent stereotactic surgery under real-time MRI guidance using the ClearPoint® system. Bilateral cerebellar dentate nuclei were targeted through a single parietal entry point with a transtentorial approach. Fifty microliters of contrast-impregnated infusate was delivered to each dentate nucleus, and adjustments were made as necessary according to real-time MRI monitoring of delivery. Perioperative clinical outcomes and postoperative volumes of distribution were recorded. RESULTS: All macaques underwent bilateral surgery successfully. Superficial pin site infection occurred in 4/17 (23.5%) subjects, which resolved with antibiotics. Two episodes of transient neurological deficit (anisocoria and unilateral weakness) were recorded, which did not require additional postoperative treatment and resolved over time. Volume of distribution of infusate achieved satisfactory coverage of target dentate nuclei, and only 1 incidence (2.9%) of cerebrospinal fluid penetration was recorded. Mean volume of distribution was 161.22 ± 39.61 mm3 (left, 173.65 ± 48.29; right, 148.80 ± 23.98). CONCLUSION: MRI-guided frameless stereotactic injection of bilateral cerebellar dentate nuclei in NHPs is safe and feasible. The use of this technique enables real-time modification of the surgical plan to achieve adequate target coverage and can be readily translated to clinical use.

Neurological Surgery Residency Programs in the United States: A National Cross-Sectional Survey.

BACKGROUND AND OBJECTIVES: The Accreditation Council for Graduate Medical Education has approved 117 neurological surgery residency programs which develop and educate neurosurgical trainees. We present the current landscape of neurosurgical training in the United States by examining multiple aspects of neurological surgery residencies in the 2022-2023 academic year and investigate the impact of program structure on resident academic productivity. METHODS: Demographic data were collected from publicly available websites and reports from the National Resident Match Program. A 34-question survey was circulated by e-mail to program directors to assess multiple features of neurological surgery residency programs, including curricular structure, fellowship availability, recent program changes, graduation requirements, and resources supporting career development. Mean resident productivity by program was collected from the literature. RESULTS: Across all 117 programs, there was a median of 2.0 (range 1.0-4.0) resident positions per year and 1.0 (range 0.0-2.0) research/elective years. Programs offered a median of 1.0 (range 0.0-7.0) Committee on Advanced Subspecialty Training-accredited fellowships, with endovascular fellowships being most frequently offered (53.8%). The survey response rate was 75/117 (64.1%). Of survey respondents, the median number of clinical sites was 3.0 (range 1.0-6.0). Almost half of programs surveyed (46.7%) reported funding mechanisms for residents, including R25, T32, and other in-house grants. Residents received a median academic stipend of $1000 (range $0-$10 000) per year. Nearly all programs (93.3%) supported wellness activities for residents, which most frequently occurred quarterly (46.7%). Annual academic stipend size was the only significant predictor of resident academic productivity (R 2 = 0.17, P = .002). CONCLUSION: Neurological surgery residency programs successfully train the next generation of neurosurgeons focusing on education, clinical training, case numbers, and milestones. These programs offer trainees the chance to tailor their career trajectories within residency, creating a rewarding and personalized experience that aligns with their career aspirations.

Cell Replacement Therapy for Brain Repair: Recent Progress and Remaining Challenges for Treating Parkinson's Disease and Cortical Injury.

Neural transplantation represents a promising approach to repairing damaged brain circuitry. Cellular grafts have been shown to promote functional recovery through "bystander effects" and other indirect mechanisms. However, extensive brain lesions may require direct neuronal replacement to achieve meaningful restoration of function. While fetal cortical grafts have been shown to integrate with the host brain and appear to develop appropriate functional attributes, the significant ethical concerns and limited availability of this tissue severely hamper clinical translation. Induced pluripotent stem cell-derived cells and tissues represent a more readily scalable alternative. Significant progress has recently been made in developing protocols for generating a wide range of neural cell types in vitro. Here, we discuss recent progress in neural transplantation approaches for two conditions with distinct design needs: Parkinson's disease and cortical injury. We discuss the current status and future application of injections of dopaminergic cells for the treatment of Parkinson's disease as well as the use of structured grafts such as brain organoids for cortical repair.

Quantifying interictal intracranial EEG to predict focal epilepsy.

Introduction: Intracranial EEG (IEEG) is used for 2 main purposes, to determine: (1) if epileptic networks are amenable to focal treatment and (2) where to intervene. Currently these questions are answered qualitatively and sometimes differently across centers. There is a need for objective, standardized methods to guide surgical decision making and to enable large scale data analysis across centers and prospective clinical trials. Methods: We analyzed interictal data from 101 patients with drug resistant epilepsy who underwent presurgical evaluation with IEEG. We chose interictal data because of its potential to reduce the morbidity and cost associated with ictal recording. 65 patients had unifocal seizure onset on IEEG, and 36 were non-focal or multi-focal. We quantified the spatial dispersion of implanted electrodes and interictal IEEG abnormalities for each patient. We compared these measures against the "5 Sense Score (5SS)," a pre-implant estimate of the likelihood of focal seizure onset, and assessed their ability to predict the clinicians' choice of therapeutic intervention and the patient outcome. Results: The spatial dispersion of IEEG electrodes predicted network focality with precision similar to the 5SS (AUC = 0.67), indicating that electrode placement accurately reflected pre-implant information. A cross-validated model combining the 5SS and the spatial dispersion of interictal IEEG abnormalities significantly improved this prediction (AUC = 0.79; p<0.05). The combined model predicted ultimate treatment strategy (surgery vs. device) with an AUC of 0.81 and post-surgical outcome at 2 years with an AUC of 0.70. The 5SS, interictal IEEG, and electrode placement were not correlated and provided complementary information. Conclusions: Quantitative, interictal IEEG significantly improved upon pre-implant estimates of network focality and predicted treatment with precision approaching that of clinical experts. We present this study as an important step in building standardized, quantitative tools to guide epilepsy surgery.

Protocol for human brain organoid transplantation into a rat visual cortex to model neural repair.

Human stem-cell-derived organoids represent a promising substrate for transplantation-based neural repair. Here, we describe a protocol for transplanting forebrain organoids into an injured adult rat visual cortex. This protocol includes surgical details for craniectomy, aspiration injury, organoid transplantation, and cranioplasty. This platform represents a valuable tool for investigating the efficacy of organoids as structured grafts for neural repair. For complete details on the use and execution of this protocol, please refer to Jgamadze et al.1.

Effect of Race and Insurance Type on Access to, and Outcomes of, Epilepsy Surgery: A Literature Review.

BACKGROUND: Despite higher rates of seizure freedom, a large proportion of patients with medically refractory seizures who could benefit from epilepsy surgery do not receive surgical treatment. This literature review describes the association of race and insurance status with epilepsy surgery access and outcomes. METHODS: Searches in Scopus and PubMed databases related to disparities in epilepsy surgery were conducted. The inclusion criteria consisted of data that could be used to compare epilepsy surgery patient access and outcomes by insurance or race in the United States. Two independent reviewers determined article eligibility. RESULTS: Of the 289 studies reviewed, 26 were included. Most of the studies were retrospective cohort studies (23 of 26) and national admissions database studies (13 of 26). Of the 17 studies that evaluated epilepsy surgery patient demographics, 11 showed that Black patients were less likely to receive surgery than were White patients or had an increased time to surgery from seizure onset. Nine studies showed that patients with private insurance were more likely to undergo epilepsy surgery and have shorter time to surgery compared with patients with public insurance. No significant association was found between the seizure recurrence rate after surgery with insurance or race. CONCLUSIONS: Black patients and patients with public insurance are receiving epilepsy surgery at lower rates after a prolonged waiting period compared with other patients with medically refractory epilepsy. These results are consistent across the current reported literature. Future efforts should focus on additional characterization and potential causes of these disparities to develop successful interventions.

Seizure onset patterns predict outcome after stereo-electroencephalography-guided laser amygdalohippocampotomy.

OBJECTIVE: Stereotactic laser amygdalohippocampotomy (SLAH) is an appealing option for patients with temporal lobe epilepsy, who often require intracranial monitoring to confirm mesial temporal seizure onset. However, given limited spatial sampling, it is possible that stereotactic electroencephalography (stereo-EEG) may miss seizure onset elsewhere. We hypothesized that stereo-EEG seizure onset patterns (SOPs) may differentiate between primary onset and secondary spread and predict postoperative seizure control. In this study, we characterized the 2-year outcomes of patients who underwent single-fiber SLAH after stereo-EEG and evaluated whether stereo-EEG SOPs predict postoperative seizure freedom. METHODS: This retrospective five-center study included patients with or without mesial temporal sclerosis (MTS) who underwent stereo-EEG followed by single-fiber SLAH between August 2014 and January 2022. Patients with causative hippocampal lesions apart from MTS or for whom the SLAH was considered palliative were excluded. An SOP catalogue was developed based on literature review. The dominant pattern for each patient was used for survival analysis. The primary outcome was 2-year Engel I classification or recurrent seizures before then, stratified by SOP category. RESULTS: Fifty-eight patients were included, with a mean follow-up duration of 39 ± 12 months after SLAH. Overall 1-, 2-, and 3-year Engel I seizure freedom probability was 54%, 36%, and 33%, respectively. Patients with SOPs, including low-voltage fast activity or low-frequency repetitive spiking, had a 46% 2-year seizure freedom probability, compared to 0% for patients with alpha or theta frequency repetitive spiking or theta or delta frequency rhythmic slowing (log-rank test, p = .00015). SIGNIFICANCE: Patients who underwent SLAH after stereo-EEG had a low probability of seizure freedom at 2 years, but SOPs successfully predicted seizure recurrence in a subset of patients. This study provides proof of concept that SOPs distinguish between hippocampal seizure onset and spread and supports using SOPs to improve selection of SLAH candidates.

Neurosurgeons Deliver Similar Quality Care Regardless of First Assistant Type: Resident Physician versus Nonphysician Surgical Assistant.

OBJECTIVE: There are limited data evaluating the outcomes of attending neurosurgeons with different types of first assistants. This study considers a common neurosurgical procedure (single-level, posterior-only lumbar fusion surgery) and examines whether attending surgeons deliver equal patient outcomes, regardless of the type of first assistant (resident physician vs. nonphysician surgical assistant [NPSA]), among otherwise exact-matched patients. METHODS: The authors retrospectively analyzed 3395 adult patients undergoing single-level, posterior-only lumbar fusion at a single academic medical center. Primary outcomes included readmissions, emergency department visits, reoperation, and mortality within 30 and 90 days after surgery. Secondary outcome measures included discharge disposition, length of stay, and length of surgery. Coarsened exact matching was used to match patients on key demographics and baseline characteristics known to independently affect neurosurgical outcomes. RESULTS: Among exact-matched patients (n = 1402), there was no significant difference in adverse postsurgical events (readmission, emergency department visits, reoperation, or mortality) within 30 days or 90 days of the index operation between patients who had resident physicians and those who had NPSAs as first assistants. Patients who had resident physicians as first assistants demonstrated a longer length of stay (mean: 100.0 vs. 87.4 hours, P < 0.001) and a shorter duration of surgery (mean: 187.4 vs. 213.8 minutes, P < 0.001). There was no significant difference between the two groups in the percentage of patients discharged home. CONCLUSIONS: For single-level posterior spinal fusion, in the setting described, there are no differences in short-term patient outcomes delivered by attending surgeons assisted by resident physicians versus NPSAs.

Distinguishing Progression from Pseudoprogression in Glioblastoma Using 18F-Fluciclovine PET.

Accurate differentiation between tumor progression (TP) and pseudoprogression remains a critical unmet need in neurooncology. 18F-fluciclovine is a widely available synthetic amino acid PET radiotracer. In this study, we aimed to assess the value of 18F-fluciclovine PET for differentiating pseudoprogression from TP in a prospective cohort of patients with suspected radiographic recurrence of glioblastoma. Methods: We enrolled 30 glioblastoma patients with radiographic progression after first-line chemoradiotherapy for whom surgical resection was planned. The patients underwent preoperative 18F-fluciclovine PET and MRI. The relative percentages of viable tumor and therapy-related changes observed in histopathology were quantified and categorized as TP (≥50% viable tumor), mixed TP (<50% and >10% viable tumor), or pseudoprogression (≤10% viable tumor). Results: Eighteen patients had TP, 4 had mixed TP, and 8 had pseudoprogression. Patients with TP/mixed TP had a significantly higher 40- to 50-min SUVmax (6.64 + 1.88 vs. 4.11 ± 1.52, P = 0.009) than patients with pseudoprogression. A 40- to 50-min SUVmax cutoff of 4.66 provided 90% sensitivity and 83% specificity for differentiation of TP/mixed TP from pseudoprogression (area under the curve [AUC], 0.86). A maximum relative cerebral blood volume cutoff of 3.672 provided 90% sensitivity and 71% specificity for differentiation of TP/mixed TP from pseudoprogression (AUC, 0.779). Combining a 40- to 50-min SUVmax cutoff of 4.66 and a maximum relative cerebral blood volume of 3.67 on MRI provided 100% sensitivity and 80% specificity for differentiating TP/mixed TP from pseudoprogression (AUC, 0.95). Conclusion: 18F-fluciclovine PET uptake can accurately differentiate pseudoprogression from TP in glioblastoma, with even greater accuracy when combined with multiparametric MRI. Given the wide availability of 18F-fluciclovine, larger, multicenter studies are warranted to determine whether amino acid PET with 18F-fluciclovine should be used in the routine posttreatment assessment of glioblastoma.

Matched Analysis of the Risk Assessment and Prediction Tool for Discharge Planning Following Single-Level Posterior Lumbar Fusion.

OBJECTIVES: Predicting patient needs for extended care after spinal fusion remains challenging. The Risk Assessment and Prediction Tool (RAPT) was externally developed to predict discharge disposition after nonspine orthopedic surgery but remains scarcely used in neurosurgery. The present study is the first to use coarsened exact matching-which incorporated patient characteristics known to independently affect outcomes-for 1:1 matching across a large population of single-level, posterior lumbar fusions, to isolate the predictive value of preoperative RAPT score on postoperative discharge disposition. METHODS: Preoperative RAPT scores were prospectively calculated for 1066 patients undergoing consecutive single-level, posterior-only lumbar fusion within a single, university healthcare system. The primary outcome was discharge disposition. Logistic regression was executed across all patients, evaluating the RAPT score as a continuous variable to predict home discharge. Subsequently, patients were retrospectively clustered into predicted risk cohorts-validated within prior orthopedic joint research-based on the RAPT score (Lowest, Intermediate, and Highest Risk). Coarsened exact matching was performed among predicted risk cohorts, and outcomes were compared between exact-matched groups. RESULTS: Among all patients, single-point increases in the RAPT score (i.e., decrease in predicted risk) were associated a 75% increased odds of home discharge (P < 0.001). Exact-matched analysis demonstrated increased odds of home discharge by 400% when comparing the Lowest versus Highest Risk cohorts (P = 0.004), by 750% when comparing the Intermediate versus Highest Risk cohorts (P < 0.001), and by 200% when comparing the Lowest versus Intermediate Risk cohorts (P < 0.001). CONCLUSIONS: The RAPT score, captured in preoperative evaluations, can be highly predictive of discharge disposition following single-level, posterior lumbar fusion.

Do-It-Yourself Augmented Reality Heads-Up Display (DIY AR-HUD): A Technical Note.

BACKGROUND: We present a "Do-It-Yourself" method to build an affordable augmented reality heads-up display system (AR-HUD) capable of displaying intraoperative images. All components are commercially available products, which the surgeons may use in their own practice for educational and research purposes. METHODS: Moverio BT 35-E smart glasses were connected to operating room imaging modalities (ie, fluoroscopy and 3D navigation platforms) via a high-definition multimedia interface (HDMI) converter, allowing for continuous high-definition video transmission. The addition of an HDMI transmitter-receiver makes the AR-HUD system wireless. RESULTS: We used our AR-HUD system in 3 patients undergoing instrumented spinal fusion. AR-HUD projected fluoroscopy images onto the surgical field, eliminating shift of surgeon focus and procedure interruption, with only a 40- to 100-ms delay in transmission, which was not clinically impactful. CONCLUSIONS: An affordable AR-HUD capable of displaying real-time information into the surgeon's view can be easily designed, built, and tested in surgical practice. As wearable heads-up display technology continues to evolve rapidly, individual components presented here may be substituted to improve its functionality and usability. Surgeons are in a unique position to conduct clinical testing in the operating room environment to optimize the augmented reality system for surgical use.

Tumor Innervation: Cancer Has Some Nerve.

Over the past decade, several landmark reports have demonstrated that the nervous system plays an active role in cancer initiation and progression. These studies demonstrate that ablation of specific nerve types (parasympathetic, sympathetic, or sensory) abrogates tumor growth in a tissue-specific manner. Further, many tumor types are more densely innervated than their normal tissues of origin. These striking results raise fundamental questions regarding tumor innervation, how it is initiated, and how it molecularly contributes to disease. In this review, we aim to address what is currently known about the origin of tumor-infiltrating nerves, how they may be recruited to tumors, and how their presence may give rise to aggressive disease.

Predicting short-term outcomes following supratentorial tumor surgery.

OBJECTIVES: The LACE+ index risk prediction tool has not been successfully used to predict short-term outcomes after neurosurgery. This study assessed the ability of LACE+ to predict 30-day (30D) adverse outcomes after supratentorial brain tumor surgery. PATIENTS AND METHODS: LACE+ scores were retrospectively calculated for consecutive patients (n = 624) who received surgery for supratentorial tumors at one multi-center health system (2017-2019). Coarsened exact matching was employed to control for confounding variables. Outcomes including unplanned hospital readmission, emergency department visits, and death were compared for patients with different LACE+ score quartiles (Q1, Q2, Q3, Q4). RESULTS: 134 patients were matched between Q1 and Q4; 152 patients between Q2 and Q4; 192 patients between Q3 and Q4. LACE+ score was not found to predict readmission within 30D of discharge for Q1 vs Q4 (p = 0.239), Q2 vs Q4 (p = 0.336), or Q3 vs Q4 (p = 0.739). LACE + score also did not predict 30D risk of emergency department visits for Q1 vs Q4 (p = 0.210), Q2 vs Q4 (p = 0.839), or Q3 vs Q4 (p = 0.167). LACE + did predict death within 30D of surgery for Q3 vs Q4 (1.04 % vs 7.29 %, p = 0.039), but not for Q1 vs Q4 (p = 0.625) or Q2 vs Q4 (p = 0.125). CONCLUSION: LACE + may not be suitable for characterizing short-term risk of certain perioperative events in a patient population undergoing supratentorial brain tumor surgery.

A Primer on Human Brain Organoids for the Neurosurgeon.

Human brain organoids emerged in 2013 as a technology that, unlike prior in Vitro neural models, recapitulates brain development with a high degree of spatial and temporal fidelity. As the platform matured with more accurate reproduction of cerebral architecture, brain organoids became increasingly valuable for studying both normal cortical neurogenesis and a variety of congenital human brain disorders. While the majority of research utilizing human brain organoids has been in the realm of basic science, clinical applications are forthcoming. These present and future translational efforts have the potential to make a considerable impact on the field of neurosurgery. For example, glioma organoids are already being used to study tumor biology and drug responses, and adaptation for the investigation of other neurosurgery-relevant diseases is underway. Moreover, organoids are being explored as a structured neural substrate for repairing brain circuitry. Thus, we believe it is important for our field to be aware and have an accurate understanding of this emerging technology. In this review, we describe the key characteristics of human brain organoids, review their relevant translational applications, and discuss the ethical implications of their use through a neurosurgical lens.

Penetrating Spinal Column Injuries (pSI): An Institutional Experience with 100 Consecutive Cases in an Urban Trauma Center.

BACKGROUND: Gunshot wound (GSW) injuries are among the leading causes of penetrating spinal column injury (pSI). Patients with pSI often have concurrent polytrauma that complicates management. METHODS: We retrospectively reviewed charts between January 2012 to June 2018 at an urban Level 1 trauma center and analyzed bracing and surgical indications, antibiotic and magnetic resonance imaging (MRI) use, and patient outcomes. RESULTS: We identified 100 patients with pSI with an average age of 27.2 (range, 15-58) years. Five patients had knife injuries and 95 suffered GSW. Polytrauma occurred in 90% of patients with an average of 3.39 bullets per patient (range, 1-23). Fourteen patients underwent either decompressive surgery (n = 8) or decompression and fusion (n = 6). Thirty-five patients were externally braced. A total of 43% of patients presented as American Spinal Injury Association-A compared with 26% who were intact. Although 14 patients received prophylactic antibiotics for retained bullets or durotomies, only 2 patients had postoperative wound infections and 4 had extraspinal infections from retained bullets. All inpatient mortalities (n = 5) were patients with cervical pSI. Thirteen patients with GSW obtained MRI scans without complications. Among our cohort, only 65 patients had follow-up with a median follow-up period of 1.25 (range, 1-60) months. CONCLUSIONS: Management of pSI in urban trauma centers is complex, as these victims routinely have polytrauma that takes precedence. Indications for surgical intervention are narrow and secondary to surgery for polytrauma. External bracing may be overutilized. The efficacy of prophylactic antibiotics remains unclear. MRI can contribute valuable information but is limited by uncertainty regarding bullet compatibility. Lack of follow-up limits the study of this population.

Association of spinal instability due to metastatic disease with increased mortality and a proposed clinical pathway for treatment.

OBJECTIVE: Multidisciplinary treatment including medical oncology, radiation oncology, and surgical consultation is necessary to provide comprehensive therapy for patients with spinal metastases. The goal of this study was to review the use of radiation therapy and/or surgical intervention and their impact on patient outcomes. METHODS: In this retrospective series, the authors identified at their institution those patients with spinal metastases who had received radiation therapy alone or had undergone surgery with or without radiation therapy within a 6-year period. Data on patient age, chemotherapy, surgical procedure, radiation therapy, Karnofsky Performance Status (KPS), primary tumor pathology, Spinal Instability Neoplastic Score (SINS), and survival after treatment were collected from the patient electronic medical records. N - 1 chi-square testing was used for comparisons of proportions. The Student t-test was used for comparisons of means. A p value < 0.05 was considered statistically significant. A survival analysis was completed using a multivariate Cox proportional hazards model. RESULTS: Two hundred thirty patients with spinal metastases were identified, 109 of whom had undergone surgery with or without radiation therapy. Among the 104 patients for whom the surgical details were reviewed, 34 (33%) had a history of preoperative radiation to the surgical site but ultimately required surgical intervention. In this surgical group, a significantly increased frequency of death within 30 days was noted for the SINS unstable patients (23.5%) as compared to that for the SINS stable patients (2.3%; p < 0.001). The SINS was a significant predictor of time to death among surgical patients (HR 1.11, p = 0.037). Preoperative KPS was not independently associated with decreased survival (p > 0.5) on univariate analysis. One hundred twenty-six patients met the criteria for inclusion in the radiation-only analysis. Ninety-eight of these patients (78%) met the criteria for potential instability (PI) at the time of treatment, according to the SINS system. Five patients (5%) with PI in the radiation therapy group had a documented neurosurgical or orthopedic surgery consultation prior to radiation therapy. CONCLUSIONS: At the authors' institution, patients with gross mechanical instability per the SINS system had an increased rate of 30-day postoperative mortality, which remained significant when controlling for other factors. Surgical consultation for metastatic spine patients receiving radiation oncology consultation with PI is low. The authors describe an institutional pathway to encourage multidisciplinary treatment from the initial encounter in the emergency department to expedite surgical evaluation and collaboration.

Undiagnosed Obstructive Sleep Apnea as Predictor of 90-Day Readmission for Brain Tumor Patients.

BACKGROUND: Previously undiagnosed obstructive sleep apnea (OSA) is a known contributor to negative postoperative outcomes. The STOP-Bang questionnaire is a screening tool for OSA that has been validated in both medical and surgical populations. The authors have previously studied this screening tool in a brain tumor population at 30 days. The present study seeks to investigate the effectiveness of this questionnaire, for predicting 90-day readmissions in a population of brain tumor patients with previously undiagnosed OSA. METHODS: Included for analysis were all patients undergoing craniotomy for supratentorial neoplasm at a multihospital, single academic medical center. Data were collected from supratentorial craniotomy cases for which the patient was alive at 90 days after surgery (n = 238). Simple logistic regression analyses were used to assess the ability of the STOP-Bang questionnaire and subsequent single variables to accurately predict patient outcomes at 90 days. RESULTS: The sample included 238 brain tumor admissions, of which 50% were female (n = 119). The average STOP-Bang score was 1.95 ± 1.24 (range 0-7). A 1-unit higher increase in STOP-Bang score accurately predicted 90-day readmissions (odds ratio [OR] = 1.65, P = 0.001), 30- to 90-day emergency department visits (OR = 1.85, P < 0.001), and 30- to 90-day reoperation (OR = 2.32, P < 0.001) with fair accuracy as confirmed by the receiver operating characteristic (C-statistic = 0.65-0.76). However, the STOP-Bang questionnaire did not correlate with home discharge (P = 0.315). CONCLUSIONS: The results of this study suggest that undiagnosed OSA, as evaluated by the STOP-Bang questionnaire, is an effective predictor of readmission risk and health system utilization in a brain tumor craniotomy population with previously undiagnosed OSA.

A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity.

Glioblastomas exhibit vast inter- and intra-tumoral heterogeneity, complicating the development of effective therapeutic strategies. Current in vitro models are limited in preserving the cellular and mutational diversity of parental tumors and require a prolonged generation time. Here, we report methods for generating and biobanking patient-derived glioblastoma organoids (GBOs) that recapitulate the histological features, cellular diversity, gene expression, and mutational profiles of their corresponding parental tumors. GBOs can be generated quickly with high reliability and exhibit rapid, aggressive infiltration when transplanted into adult rodent brains. We further demonstrate the utility of GBOs to test personalized therapies by correlating GBO mutational profiles with responses to specific drugs and by modeling chimeric antigen receptor T cell immunotherapy. Our studies show that GBOs maintain many key features of glioblastomas and can be rapidly deployed to investigate patient-specific treatment strategies. Additionally, our live biobank establishes a rich resource for basic and translational glioblastoma research.

Transplantation of Human Brain Organoids: Revisiting the Science and Ethics of Brain Chimeras.

Recent demonstrations of human brain organoid transplantation in rodents have accentuated ethical concerns associated with these entities, especially as they relate to potential "humanization" of host animals. Consideration of established scientific principles can help define the realistic range of expected outcomes in such transplantation studies. This practical approach suggests that augmentation of discrete brain functions in transplant hosts is a more relevant ethical question in the near term than the possibility of "conscious" chimeric animals. We hope that this framework contributes to a balanced approach for proceeding with studies involving brain organoid transplantation and other forms of human-animal brain chimeras.

Association of Overlapping Neurosurgery With Patient Outcomes at a Large Academic Medical Center.

BACKGROUND: Limited data exist on the safety of overlapping surgery, a practice that has recently received widespread attention. OBJECTIVE: To examine the association of overlapping neurosurgery with patient outcomes. METHODS: A total of 3038 routinely scheduled, elective neurosurgical procedures were retrospectively reviewed at a single, multihospital academic medical center. Procedures were categorized into any overlap or no overlap and further subcategorized into beginning overlap (first 50% of procedure only), end overlap (last 50% of procedure only), and middle overlap (overlap at the midpoint). RESULTS: A total of 1030 (33.9%) procedures had any overlap, whereas 278 (9.2%) had beginning overlap, 190 (6.3%) had end overlap, and 476 (15.7%) had middle overlap. Compared with no overlap patients, patients with any overlap had lower American Society of Anesthesiologists scores (P = .0018), less prior surgery (P < .0001), and less prior neurosurgery (P < .0001), though they tended to be older (P < .0001) and more likely in-patients (P = .0038). Any-overlap patients had decreased overall mortality (2.8% vs 4.5%; P = .025), 30- to 90-d readmission rate (3.1% vs 5.5%; P = .0034), 30- to 90-d reoperation rate (1.0% vs 2.0%; P = .03), 30- to 90-d emergency room (ER) visit rate (2.1% vs 3.7%; P = .018), and future surgery on index admission (2.8% vs 7.3%; P < .0001). Multiple regression analysis validated noninferior outcomes for overlapping surgery, except for the association of increased future surgery on index admission with middle overlap (odds ratio 3.99; 95% confidence interval [1.91, 8.33]). CONCLUSION: Overlapping neurosurgery is associated with noninferior patient outcomes that may be driven by surgeon selection of healthier patients, regardless of specific overlap timing.