Leveraging single-cell sequencing to classify and characterize tumor subgroups in bulk RNA-sequencing data.

PURPOSE: Accurate classification of cancer subgroups is essential for precision medicine, tailoring treatments to individual patients based on their cancer subtypes. In recent years, advances in high-throughput sequencing technologies have enabled the generation of large-scale transcriptomic data from cancer samples. These data have provided opportunities for developing computational methods that can improve cancer subtyping and enable better personalized treatment strategies. METHODS: Here in this study, we evaluated different feature selection schemes in the context of meningioma classification. To integrate interpretable features from the bulk (n = 77 samples) and single-cell profiling (∼ 10 K cells), we developed an algorithm named CLIPPR which combines the top-performing single-cell models, RNA-inferred copy number variation (CNV) signals, and the initial bulk model to create a meta-model. RESULTS: While the scheme relying solely on bulk transcriptomic data showed good classification accuracy, it exhibited confusion between malignant and benign molecular classes in approximately ∼ 8% of meningioma samples. In contrast, models trained on features learned from meningioma single-cell data accurately resolved the sub-groups confused by bulk-transcriptomic data but showed limited overall accuracy. CLIPPR showed superior overall accuracy and resolved benign-malignant confusion as validated on n = 789 bulk meningioma samples gathered from multiple institutions. Finally, we showed the generalizability of our algorithm using our in-house single-cell (∼ 200 K cells) and bulk TCGA glioma data (n = 711 samples). CONCLUSION: Overall, our algorithm CLIPPR synergizes the resolution of single-cell data with the depth of bulk sequencing and enables improved cancer sub-group diagnoses and insights into their biology.

Targeting GBM with an Oncolytic Picornavirus SVV-001 alone and in combination with fractionated Radiation in a Novel Panel of Orthotopic PDX models.

BACKGROUND: Animal models representing different molecular subtypes of glioblastoma multiforme (GBM) is desired for developing new therapies. SVV-001 is an oncolytic virus selectively targeting cancer cells. It's capacity of passing through the blood brain barrier makes is an attractive novel approach for GBM. MATERIALS AND METHODS: 23 patient tumor samples were implanted into the brains of NOD/SCID mice (1 × 105 cells/mouse). Tumor histology, gene expression (RNAseq), and growth rate of the developed patient-derived orthotopic xenograft (PDOX) models were compared with the originating patient tumors during serial subtransplantations. Anti-tumor activities of SVV-001 were examined in vivo; and therapeutic efficacy validated in vivo via single i.v. injection (1 × 1011 viral particle) with or without fractionated (2 Gy/day x 5 days) radiation followed by analysis of animal survival times, viral infection, and DNA damage. RESULTS: PDOX formation was confirmed in 17/23 (73.9%) GBMs while maintaining key histopathological features and diffuse invasion of the patient tumors. Using differentially expressed genes, we subclassified PDOX models into proneural, classic and mesenchymal groups. Animal survival times were inversely correlated with the implanted tumor cells. SVV-001 was active in vitro by killing primary monolayer culture (4/13 models), 3D neurospheres (7/13 models) and glioma stem cells. In 2/2 models, SVV-001 infected PDOX cells in vivo without harming normal brain cells and significantly prolonged survival times in 2/2 models. When combined with radiation, SVV-001 enhanced DNA damages and further prolonged animal survival times. CONCLUSION: A panel of 17 clinically relevant and molecularly annotated PDOX modes of GBM is developed, and SVV-001 exhibited strong anti-tumor activities in vitro and in vivo.

Integrated clinical genomic analysis reveals xenobiotic metabolic genes are downregulated in meningiomas of current smokers.

INTRODUCTION: Meningiomas are the most common primary intracranial tumor. Recently, various genetic classification systems for meningioma have been described. We sought to identify clinical drivers of different molecular changes in meningioma. As such, clinical and genomic consequences of smoking in patients with meningiomas remain unexplored. METHODS: 88 tumor samples were analyzed in this study. Whole exome sequencing (WES) was used to assess somatic mutation burden. RNA sequencing data was used to identify differentially expressed genes (DEG) and genes sets (GSEA). RESULTS: Fifty-seven patients had no history of smoking, twenty-two were past smokers, and nine were current smokers. The clinical data showed no major differences in natural history across smoking status. WES revealed absence of AKT1 mutation rate in current or past smokers compared to non-smokers (p = 0.046). Current smokers had increased mutation rate in NOTCH2 compared to past and never smokers (p < 0.05). Mutational signature from current and past smokers showed disrupted DNA mismatch repair (cosine-similarity = 0.759 and 0.783). DEG analysis revealed the xenobiotic metabolic genes UGT2A1 and UGT2A2 were both significantly downregulated in current smokers compared to past (Log2FC = - 3.97, padj = 0.0347 and Log2FC = - 4.18, padj = 0.0304) and never smokers (Log2FC = - 3.86, padj = 0.0235 and Log2FC = - 4.20, padj = 0.0149). GSEA analysis of current smokers showed downregulation of xenobiotic metabolism and enrichment for G2M checkpoint, E2F targets, and mitotic spindle compared to past and never smokers (FDR < 25% each). CONCLUSION: In this study, we conducted a comparative analysis of meningioma patients based on their smoking history, examining both their clinical trajectories and molecular changes. Meningiomas from current smokers were more likely to harbor NOTCH2 mutations, and AKT1 mutations were absent in current or past smokers. Moreover, both current and past smokers exhibited a mutational signature associated with DNA mismatch repair. Meningiomas from current smokers demonstrate downregulation of xenobiotic metabolic enzymes UGT2A1 and UGT2A2, which are downregulated in other smoking related cancers. Furthermore, current smokers exhibited downregulation xenobiotic metabolic gene sets, as well as enrichment in gene sets related to mitotic spindle, E2F targets, and G2M checkpoint, which are hallmark pathways involved in cell division and DNA replication control. In aggregate, our results demonstrate novel alterations in meningioma molecular biology in response to systemic carcinogens.

XCVATR: detection and characterization of variant impact on the Embeddings of single -cell and bulk RNA-sequencing samples.

BACKGROUND: RNA-sequencing has become a standard tool for analyzing gene activity in bulk samples and at the single-cell level. By increasing sample sizes and cell counts, this technique can uncover substantial information about cellular transcriptional states. Beyond quantification of gene expression, RNA-seq can be used for detecting variants, including single nucleotide polymorphisms, small insertions/deletions, and larger variants, such as copy number variants. Notably, joint analysis of variants with cellular transcriptional states may provide insights into the impact of mutations, especially for complex and heterogeneous samples. However, this analysis is often challenging due to a prohibitively high number of variants and cells, which are difficult to summarize and visualize. Further, there is a dearth of methods that assess and summarize the association between detected variants and cellular transcriptional states. RESULTS: Here, we introduce XCVATR (eXpressed Clusters of Variant Alleles in Transcriptome pRofiles), a method that identifies variants and detects local enrichment of expressed variants within embedding of samples and cells in single-cell and bulk RNA-seq datasets. XCVATR visualizes local "clumps" of small and large-scale variants and searches for patterns of association between each variant and cellular states, as described by the coordinates of cell embedding, which can be computed independently using any type of distance metrics, such as principal component analysis or t-distributed stochastic neighbor embedding. Through simulations and analysis of real datasets, we demonstrate that XCVATR can detect enrichment of expressed variants and provide insight into the transcriptional states of cells and samples. We next sequenced 2 new single cell RNA-seq tumor samples and applied XCVATR. XCVATR revealed subtle differences in CNV impact on tumors. CONCLUSIONS: XCVATR is publicly available to download from https://github.com/harmancilab/XCVATR .

Molecular profiling predicts meningioma recurrence and reveals loss of DREAM complex repression in aggressive tumors.

Meningiomas account for one-third of all primary brain tumors. Although typically benign, about 20% of meningiomas are aggressive, and despite the rigor of the current histopathological classification system there remains considerable uncertainty in predicting tumor behavior. Here, we analyzed 160 tumors from all 3 World Health Organization (WHO) grades (I through III) using clinical, gene expression, and sequencing data. Unsupervised clustering analysis identified 3 molecular types (A, B, and C) that reliably predicted recurrence. These groups did not directly correlate with the WHO grading system, which classifies more than half of the tumors in the most aggressive molecular type as benign. Transcriptional and biochemical analyses revealed that aggressive meningiomas involve loss of the repressor function of the DREAM complex, which results in cell-cycle activation; only tumors in this category tend to recur after full resection. These findings should improve our ability to predict recurrence and develop targeted treatments for these clinically challenging tumors.

Predicting surgical decision-making in vestibular schwannoma using tree-based machine learning.

OBJECTIVE: Vestibular schwannomas (VSs) are the most common neoplasm of the cerebellopontine angle in adults. Though these lesions are generally slow growing, their growth patterns and associated symptoms can be unpredictable, which may complicate the decision to pursue conservative management versus active intervention. Additionally, surgical decision-making can be controversial because of limited high-quality evidence and multiple quality-of-life considerations. Machine learning (ML) is a powerful tool that utilizes data sets to essentialize multidimensional clinical processes. In this study, the authors trained multiple tree-based ML algorithms to predict the decision for active treatment versus MRI surveillance of VS in a single institutional cohort. In doing so, they sought to assess which preoperative variables carried the most weight in driving the decision for intervention and could be used to guide future surgical decision-making through an evidence-based approach. METHODS: The authors reviewed the records of patients who had undergone evaluation by neurosurgery and otolaryngology with subsequent active treatment (resection or radiation) for unilateral VS in the period from 2009 to 2021, as well as those of patients who had been evaluated for VS and were managed conservatively throughout 2021. Clinical presentation, radiographic data, and management plans were abstracted from each patient record from the time of first evaluation until the last follow-up or surgery. Each encounter with the patient was treated as an instance involving a management decision that depended on demographics, symptoms, and tumor profile. Decision tree and random forest classifiers were trained and tested to predict the decision for treatment versus imaging surveillance on the basis of unseen data using an 80/20 pseudorandom split. Predictor variables were tuned to maximize performance based on lowest Gini impurity indices. Model performance was optimized using fivefold cross-validation. RESULTS: One hundred twenty-four patients with 198 rendered decisions concerning management were included in the study. In the decision tree analysis, only a maximum tumor dimension threshold of 1.6 cm and progressive symptoms were required to predict the decision for treatment with 85% accuracy. Optimizing maximum dimension thresholds and including age at presentation boosted accuracy to 88%. Random forest analysis (n = 500 trees) predicted the decision for treatment with 80% accuracy. Factors with the highest variable importance based on multiple measures of importance, including mean minimal conditional depth and largest Gini impurity reduction, were maximum tumor dimension, age at presentation, Koos grade, and progressive symptoms at presentation. CONCLUSIONS: Tree-based ML was used to predict which factors drive the decision for active treatment of VS with 80%-88% accuracy. The most important factors were maximum tumor dimension, age at presentation, Koos grade, and progressive symptoms. These results can assist in surgical decision-making and patient counseling. They also demonstrate the power of ML algorithms in extracting useful insights from limited data sets.

Varied histomorphology and clinical outcomes of FGFR3-TACC3 fusion gliomas.

Targeted therapies for driver gene fusions in cancers have yielded substantial improvements in care. Here, the authors outline a case series of 6 patients with FGFR3-TACC3 fusion in primary brain tumors ranging from polymorphous low-grade neuroepithelial tumor of the young to papillary glioneuronal tumors and glioblastoma (GBM). Previous studies indicated the FGFR3-TACC3 fusion provides survival benefit to GBM patients. Consistent with this, 2 patients with GBM had unexpectedly good outcomes and survived for 5 and 7 years, respectively. In contrast, 2 patients with initially lower graded tumors survived only 3 years and 1 year, respectively. One patient received erdafitinib, a targeted FGFR inhibitor, for 3 months at late disease recurrence and no response was seen. There were varied histomorphological features, including many cases that lacked the characteristic FGFR3-TACC3 pathology. The findings of this cohort suggest that molecular testing is justified, even for glioma cases lacking classic histopathological signatures. Currently, FGFR3-TACC3 fusion gliomas are often classified on the basis of histopathological features. However, further research is needed to examine whether IDH1/2-wild-type tumors with FGFR3-TACC3 fusion should be classified as a subtype on the basis of this molecular fusion. Because patients with IDH1/2-wild-type GBM with FGFR3-TACC3 fusion have improved survival, routine molecular testing for this mutation in patients enrolled in clinical trials and subsequent stratification may be warranted.

Forniceal deep brain stimulation rescues hippocampal memory in Rett syndrome mice.

Deep brain stimulation (DBS) has improved the prospects for many individuals with diseases affecting motor control, and recently it has shown promise for improving cognitive function as well. Several studies in individuals with Alzheimer disease and in amnesic rats have demonstrated that DBS targeted to the fimbria-fornix, the region that appears to regulate hippocampal activity, can mitigate defects in hippocampus-dependent memory. Despite these promising results, DBS has not been tested for its ability to improve cognition in any childhood intellectual disability disorder. Such disorders are a pressing concern: they affect as much as 3% of the population and involve hundreds of different genes. We proposed that stimulating the neural circuits that underlie learning and memory might provide a more promising route to treating these otherwise intractable disorders than seeking to adjust levels of one molecule at a time. We therefore studied the effects of forniceal DBS in a well-characterized mouse model of Rett syndrome (RTT), which is a leading cause of intellectual disability in females. Caused by mutations that impair the function of MeCP2 (ref. 6), RTT appears by the second year of life in humans, causing profound impairment in cognitive, motor and social skills, along with an array of neurological features. RTT mice, which reproduce the broad phenotype of this disorder, also show clear deficits in hippocampus-dependent learning and memory and hippocampal synaptic plasticity. Here we show that forniceal DBS in RTT mice rescues contextual fear memory as well as spatial learning and memory. In parallel, forniceal DBS restores in vivo hippocampal long-term potentiation and hippocampal neurogenesis. These results indicate that forniceal DBS might mitigate cognitive dysfunction in RTT.

Identification of novel fusion transcripts in meningioma.

INTRODUCTION: Meningiomas are the most common primary intracranial tumor. Recent next generation sequencing analyses have elaborated the molecular drivers of this disease. We aimed to identify and characterize novel fusion genes in meningiomas. METHODS: We performed a secondary analysis of our RNA sequencing data of 145 primary meningioma from 140 patients to detect fusion genes. Semi-quantitative rt-PCR was performed to confirm transcription of the fusion genes in the original tumors. Whole exome sequencing was performed to identify copy number variations within each tumor sample. Comparative RNA seq analysis was performed to assess the clonality of the fusion constructs within the tumor. RESULTS: We detected six fusion events (NOTCH3-SETBP1, NF2-SPATA13, SLC6A3-AGBL3, PHF19-FOXP2 in two patients, and ITPK1-FBP2) in five out of 145 tumor samples. All but one event (NF2-SPATA13) led to extremely short reading frames, making these events de facto null alleles. Three of the five patients had a history of childhood radiation. Four out of six fusion events were detected in expression type C tumors, which represent the most aggressive meningioma. We validated the presence of the RNA transcripts in the tumor tissue by semi-quantitative RT PCR. All but the two PHF19-FOXP2 fusions demonstrated high degrees of clonality. CONCLUSIONS: Fusion genes occur infrequently in meningiomas and are more likely to be found in tumors with greater degree of genomic instability (expression type C) or in patients with history of cranial irradiation.

Virtual education in neurosurgery during the COVID-19 pandemic.

OBJECTIVE: Neurosurgical education in the US has changed significantly as a consequence of the novel coronavirus (COVID-19) pandemic. Institutional social distancing requirements have resulted in many neurosurgical programs utilizing video conferencing for educational activities. However, it is unclear how or if these practices should continue after the pandemic. The objective of this study was to characterize virtual education in neurosurgery and understand how it should be utilized after COVID-19. METHODS: A 24-question, 3-part online survey was administered anonymously to all 117 US neurosurgical residency programs from May 15, 2020, to June 15, 2020. Questions pertained to the current use of virtual conferencing, preferences over traditional conferences, and future inclinations. The Likert scale (1 = strongly disagree, 3 = neutral, 5 = strongly agree) was used. Comparisons were calculated using the Mann-Whitney U-test. Statistical significance was set at 0.05. RESULTS: One-hundred eight responses were recorded. Overall, 38 respondents (35.2%) were attendings and 70 (64.8%) were trainees. Forty-one respondents (38.0%) indicated attending 5-6 conferences per week and 70 (64.8%) attend national virtual conferences. When considering different conference types, there was no overall preference (scores < 3) for virtual conferences over traditional conferences. In regard to future use, respondents strongly agreed that they would continue the practice at some capacity after the pandemic (median score 5). Overall, respondents agreed that virtual conferences would partially replace traditional conferences (median score 4), whereas they strongly disagreed with the complete replacement of traditional conferences (median score 1). The most common choices for the partial replacement of tradition conferences were case conferences (59/108, 55%) and board preparation (64/108, 59%). Lastly, there was a significant difference in scores for continued use of virtual conferencing in those who attend nationally sponsored conferences (median score 5, n = 70) and those who do not (median score 4, n = 38; U = 1762.50, z = 2.97, r = 0.29, p = 0.003). CONCLUSIONS: Virtual conferences will likely remain an integral part of neurosurgical education after the COVID-19 pandemic has abated. Across the country, residents and faculty report a preference for continued use of virtual conferencing, especially virtual case conferences and board preparation. Some traditional conferences may even be replaced with virtual conferences, in particular those that are more didactic. Furthermore, nationally sponsored virtual conferences have a positive effect on the preferences for continued use of virtual conferences.

Ambulatory neurosurgery in the COVID-19 era: patient and provider satisfaction with telemedicine.

OBJECTIVE: Telemedicine has rapidly expanded in the recent years as technologies have afforded healthcare practitioners the ability to diagnose and treat patients remotely. Due to the COVID-19 pandemic, nonessential clinical visits were greatly limited, and much of the outpatient neurosurgical practice at the authors' institution was shifted quickly to telehealth. Although there are prior data suggesting that the use of telemedicine is satisfactory in other surgical fields, data in neurosurgery are limited. This study aimed to investigate both patient and provider satisfaction with telemedicine and its strengths and limitations in outpatient neurosurgery visits. METHODS: This quality improvement study was designed to analyze provider and patient satisfaction with telemedicine consultations in an outpatient neurosurgery clinic setting at a tertiary care, large-volume, academic center. The authors designed an 11-question survey for neurosurgical providers and a 13-question survey for patients using both closed 5-point Likert scale responses and multiple choice responses. The questionnaires were administered to patients and providers during the period when the clinic restricted in-person visits. At the conclusion of the study, the overall data were analyzed qualitatively and quantitatively. RESULTS: During the study period, 607 surveys were sent out to patients seen by telehealth at the authors' academic center, and 122 responses were received. For the provider survey, 85 surveys were sent out to providers at the authors' center and other academic centers, and 40 surveys were received. Ninety-two percent of patients agreed or strongly agreed that they were satisfied with that particular telehealth visit. Eighty-eight percent of patients agreed that their telehealth visit was more convenient for them than an in-person visit, but only 36% of patients stated they would like their future visits to be telehealth. Sixty-three percent of providers agreed that telehealth visits were more convenient for them than in-person visits, and 85% of responding providers stated that they wished to incorporate telehealth into their future practice. CONCLUSIONS: Although the authors' transition to telehealth was both rapid and unexpected, most providers and patients reported positive experiences with their telemedicine visits and found telemedicine to be an effective form of ambulatory neurosurgical care. Not all patients preferred telemedicine visits over in-person visits, but the high satisfaction with telemedicine by both providers and patients is promising to the future expansion of telehealth in ambulatory neurosurgery.

Gastrointestinal stromal tumor with intracranial metastasis: case presentation and systematic review of literature.

BACKGROUND: Intracranial metastasis of Gastrointestinal Stromal Tumors (GISTs) is rare but presents unique treatment challenges. We present a case of intracranial metastasis of GIST with a systematic review of the literature. A literature search using key terms "'gastrointestinal stromal tumor' AND brain AND metastasis"" was conducted through May 2019 via Embase and Pubmed according to PRISMA guidelines. Only cases describing intradural metastases rather than calvarial or intraorbital metastases were included. CASE PRESENTATION: A 57-year-old woman with history of GIST metastatic to the liver presented with a six-week history of left facial weakness, left hearing loss, and left facial numbness, and a one-week history of headaches, gait disturbance, and dizziness. MRI revealed a contrast-enhancing dural-based left middle cranial fossa mass measuring 2.9 cm × 3.1 cm × 3.4 cm with extension into the internal auditory canal and cerebral edema. A left temporal craniotomy was performed to excise the lesion, and the patient was discharged to a rehabilitation facility at her preoperative baseline. Intraoperative pathology revealed a spindle cell neoplasm, postoperative MRI demonstrated gross total resection of the lesion, and microscopic analysis demonstrated sheets of spindled tumor cells with short ovoid, irregular, hyperchromatic nuclei and scattered large atypical nuclei without extensive necrosis. Immunohistochemical staining was positive for KIT proto-oncogene (CD117, c-KIT), and the patient was put on imatinib (400 mg/day). CONCLUSIONS: Of the 18 cases analyzed and our present case, metastasis typically involved the cerebrum with only one in infratentorial elements. The tumors in seven of the cases involved the dura, and one case metastasized to the pituitary. Eight patients died following treatment. Surgery remains the mainstay of intracranial metastatic GIST, however there are many reports of good responses to radiation or chemotherapy alone. More investigation is required to determine the best treatment course for these patients.

Treatment strategies for glioblastoma in older patients: age is just a number.

BACKGROUND/PURPOSE: Optimal care for elderly patients with glioblastoma (GBM) remains in question due to their exclusion from and underrepresentation in many clinical trials (including EORTC 22,981) as well as their historically poor overall survival. METHODS: A retrospective chart review was conducted at a single high-volume cancer center for newly diagnosed elderly (65 years old or older) GBM patients diagnosed from 2011 through 2017. RESULTS: A total of 158 newly diagnosed GBM patients aged 65 years and older were identified. One hundred forty-four patients (91.1%) received radiotherapy (RT) and 130 patients (90.3%) received concurrent temozolomide with RT. Sixty-one patients (38.6%) completed concurrent chemoradiation and 6 cycles of adjuvant temozolomide. 23% of patients discontinued temozolomide during concurrent or adjuvant treatment due to side effects or complications of chemotherapy. With a median follow-up time of 35.0 months, median overall survival (OS) time for the full cohort was 18.6 months, with estimated OS rates of 74.8%, 35.9%, and 9.5% at 1, 2, and 5 years, respectively. On multivariable analysis, higher KPS (p = 0.002, HR 0.46; 95% CI 0.63-0.82), completing planned RT course (p = 0.01, HR 0.29; 95% CI 0.11-0.75), and completing 6 cycles of adjuvant temozolomide (p = 0.01, HR 2.62; 95% CI 1.67-4.12) were independently associated with improved OS. CONCLUSIONS: Our cohort of elderly GBM patients was predominantly treated with standard of care therapy based on EORTC 22,981. Despite their age, these patients generally tolerated treatment well and had favorable outcomes compared to those reported for patients treated on EORTC 22,981. Based on these findings, using advanced age as the basis for treatment de-escalation or as an exclusionary criterion in clinical trials should be discouraged.

Effect of health disparities on overall survival of patients with glioblastoma.

BACKGROUND: Examine the potential effects of health disparities in survival of glioblastoma (GB) patients. METHODS: We conducted a retrospective chart review of newly diagnosed GB patients from 2000 to 2015 at a free standing dedicated cancer center (MD Anderson Cancer Center-MDACC) and a safety net county hospital (Ben Taub General Hospital-BT) located in Houston, Texas. We obtained demographics, insurance status, extent of resection, treatments, and other known prognostic variables (Karnofsky Score-KPS) to evaluate their role on overall GB survival (OS). RESULTS: We identified 1073 GB patients consisting of 177 from BT and 896 from MDACC. We found significant differences by ethnicity, insurance status, KPS at diagnosis, extent of resection, and percentage of patients receiving standard of care (SOC) between the two centers. OS was 1.64 years for MDACC patients and 1.24 years for BT patients (p < 0.0176). Only 81 (45.8%) BT patients received SOC compared to 577 (64%) of MDACC patients (p < 0.0001). However, there was no significant difference in OS for patients who received SOC, 1.84 years for MDACC patients and 1.99 years for BT patients (p < 0.4787). Of the 96 BT patients who did not receive SOC, 29 (30%) had KPS less than 70 at time of diagnosis and 77 (80%) lacked insurance. CONCLUSIONS: GB patients treated at a safety net county hospital had similar OS compared to a free standing comprehensive cancer center when receiving SOC. County hospital patients had poorer KPS at diagnosis and were often lacking health insurance affecting their ability to receive SOC.

Rh-BMP-2 for L5-S1 arthrodesis in long fusions to the pelvis for neuromuscular spinal deformity in the pediatric age group: analysis of 11 patients.

PURPOSE: Neuromuscular scoliosis is a challenging pathology to treat with high incidence of complications and failure of surgical fusion. Surgical correction can entail long fusion constructs extending to the pelvis. We report our experience in the use of bone morphogenetic protein (BMP) to augment L5-S1 arthrodesis in long segment fusions in pediatric patients with neuromuscular scoliosis. METHODS: Retrospective review of 11 pediatric patients with neuromuscular spinal deformity (mean, age 13.7 years; range, 10-20 years) who underwent long (mean, 15 levels; range, 10-18 levels) spinal instrumentation and fusion to the pelvis at a single institution from 2007 to 2012 with an average follow-up of 34 months (range, 11-62 months). RESULTS: Of the 11 patients, one had pseudoarthrosis at L5-S1. The average coronal Cobb angle measured 59° before surgery and 42° immediately after surgery. The average preoperative thoracic kyphosis and lumbar sagittal lordosis measured 34 and 59°, respectively. Immediately after surgery, the thoracic and lumbar angles measured 28 and 39°, respectively. At last follow-up, the average coronal Cobb angle was maintained at 43° and the thoracic and lumbar sagittal angles were 28 and 44°, respectively. An average of 14.2 mg of recombinant human bone morphogenetic protein-2 (rh-BMP-2) was used for each case. CONCLUSIONS: L5-S1 arthrodesis may be effectively achieved in long fusions for pediatric neuromuscular spinal deformity with posterolateral fusion supplemented with rh-BMP-2. This surgical strategy may be associated with lower complication rates, decreased blood loss, and shorter operative times than circumferential fusion, which is particularly important in this complex fragile patient population.

Virtual Interviews in Neurosurgery Resident Selection: A Follow-up Report.

BACKGROUND: The 2021 U.S. neurosurgery residency match interviews were conducted virtually; we surveyed applicants and interviewers to determine satisfaction with that virtual interview process. Subsequently, we conducted a follow-up survey to determine satisfaction with the virtual interview process after the residency match for faculty interviewers and 2022 interns. METHODS: A 22-question online faculty survey was sent to 116 U.S. neurosurgery training programs. A 26-question survey was sent to these programs for distribution to their intern classes. Data were analyzed quantitatively, including mean Likert score. Open-ended questionnaire responses were reviewed to identify themes. RESULTS: Overall, 32 interns representing 20 programs and 73 faculty representing 62 programs responded. Most respondents agreed that virtual interviews were more convenient (86% faculty, 90% interns) and cost-effective (100% interns) than in-person interviews. Faculty respondents agreed or strongly agreed that virtual interviews were effective to evaluate applicants' competence as residents (44%); fewer faculty agreed or strongly agreed that virtual interviews were an effective way to evaluate candidates' fit in the program (27%). For interns, 44% agreed or strongly agreed that virtual interviews gave them a good sense of the program faculty; 75% agreed or strongly agreed they were satisfied with the process related to where they matched. CONCLUSIONS: Virtual interviews offer an advantage in terms of time and cost but potentially at the expense of adequate faculty assessment of candidates' "fit" within a program's culture. Despite this, interns undergoing an all-virtual interview process report high satisfaction with the results of the residency match.

Firearm-Related Traumatic Brain Injuries in Adults: A Scoping Review.

BACKGROUND AND OBJECTIVES: Firearm-related traumatic brain injury (TBI) has emerged as a significant public health issue in the United States, coinciding with a rapid increase in gun-related deaths. This scoping review aims to update our understanding of firearm-related TBI in adult populations. METHODS: A comprehensive search of 6 online databases yielded 22 studies that met the inclusion criteria. The reviewed studies predominantly focused on young adult men who were victims of assault, although other vulnerable populations were also affected. RESULTS: Key factors in evaluating patients with firearm-related TBI included low Glasgow Coma Scale scores, central nervous system involvement, hypotension, and coagulopathies at presentation. Poor outcomes in firearm-related TBIs were influenced by various factors, including the location and trajectory of the gunshot wound, hypercoagulability, hemodynamic instability, insurance status, and specific clinical findings at hospital admission. CONCLUSION: Proposed interventions aimed to reduce the incidence and mortality of penetrating TBIs, including medical interventions such as coagulopathy reversal and changes to prehospital stabilization procedures. However, further research is needed to demonstrate the effectiveness of these interventions. The findings of this scoping review hope to inform future policy research, advocacy efforts, and the training of neurosurgeons and other treating clinicians in the management of firearm-related TBI.