Genomic Alterations in Molecularly Defined Oligodendrogliomas.

BACKGROUND AND OBJECTIVES: Oligodendrogliomas are defined by IDH1/2 mutation and codeletion of chromosome arms 1p/19q. Although previous studies identified CIC, FUBP1, and TERTp as frequently altered in oligodendrogliomas, the clinical relevance of these molecular signatures is unclear. Moreover, previous studies predominantly used research panels that are not readily available to providers and patients. Accordingly, we explore genomic alterations in molecularly defined oligodendrogliomas using clinically standardized next-generation sequencing (NGS) panels. METHODS: A retrospective single-center study evaluated adults with pathologically confirmed IDH-mutant, 1p/19q-codeleted oligodendrogliomas diagnosed between 2005 and 2021. Genetic data from formalin-fixed, paraffin-embedded specimens were analyzed with the NGS Solid Tumor Panel at the Johns Hopkins Medical Laboratories, which tests more than 400 cancer-related genes. Kaplan-Meier plots and log-rank tests compared progression-free survival (PFS) and overall survival by variant status. χ2 tests, t-tests, and Wilcoxon rank-sum tests were used to compare clinical characteristics between genomic variant status in the 10 most frequently altered genes. RESULTS: Two hundred and seventy-seven patients with molecularly defined oligodendrogliomas were identified, of which 95 patients had available NGS reports. Ten genes had 9 or more patients with a genomic alteration, with CIC, FUBP1, and TERTp being the most frequently altered genes (n = 60, 23, and 22, respectively). Kaplan-Meier curves showed that most genes were not associated with differences in PFS or overall survival. At earlier time points (PFS <100 months), CIC alterations conferred a reduction in PFS in patients (P = .038). CONCLUSION: Our study confirms the elevated frequency of CIC, FUBP1, and TERTp alterations in molecularly defined oligodendrogliomas and suggests a potential relationship of CIC alteration to PFS at earlier time points. Understanding these genomic variants may inform prognosis or therapeutic recommendations as NGS becomes routine.

Machine Learning Identifies Variation in Timing of Palliative Care Consultations Among Traumatic Brain Injury Patients.

Background and Objective Timely palliative care involvement offers demonstrable benefits for traumatic brain injury (TBI) patients; however, palliative care consultations (PCCs) are used inconsistently during TBI management. This study aimed to employ advanced machine learning techniques to elucidate the primary drivers of PCC timing variability for TBI patients. Methods Data on admission, hospital course, and outcomes were collected for a cohort of 232 TBI patients who received both PCCs and neurosurgical consultations during the same hospitalization. Principal Component Analysis (PCA) and K-means clustering were used to identify patient phenotypes, which were then compared using Kaplan-Meier analysis. An extreme gradient boosting model (XGBoost) was employed to determine drivers of PCC timing, with model interpretation performed using SHapley Additive exPlanations (SHAP). Results Cluster A (n = 86) consisted mainly of older (median [IQR] = 87 [78, 94] years), White females with mild TBIs and demonstrated the shortest time-to-PCC (2.5 [1.0, 7.0] days). Cluster B (n = 108) also sustained mild TBIs but comprised moderately younger (81 [75, 86] years) married White males with later PCC (5.0 [3.0, 10.8] days). Cluster C (n = 38) represented much younger (46.5 [29.5, 59.8] years), more severely injured, non-White patients with the latest PCC initiation (9.0 [4.2, 17.0] days). The clusters did not differ by discharge disposition (p = 0.4) or frequency inpatient mortality (p > 0.9); however, Kaplan-Meier analysis revealed a significant difference in the time from admission to PCC (p < 0.001), despite no differences in time from admission to mortality (p = 0.18). SHAP analysis of the XGBoost model identified age, sex, and race as the most influential drivers of PCC timing. Conclusions This study highlights crucial disparities in PCC timing for TBI patients and underscores the need for targeted strategies to ensure timely and equitable palliative care integration for this vulnerable population.

Perceived Barriers to Pursuing a Career in Neurosurgery in Nigeria: A Cross-Sectional Survey of Nigerian Medical Students and Unspecialized Physicians.

BACKGROUND: Nigeria has an inadequate number of neurosurgeons to meet the population's demand for neurosurgical care. Furthermore, few Nigerian neurosurgeons are female. This study sought to evaluate perceived barriers to pursuing neurosurgery among Nigerian trainees. METHODS: A 60-question survey was distributed electronically to medical students at the College of Medicine, University of Ibadan, and unspecialized intern physicians at the University College Hospital, Ibadan, Nigeria. Participation was voluntary. RESULTS: One hundred fifty-seven respondents participated in the survey. A greater proportion of males indicated an interest in neurosurgery than females (40% vs. 18%, P = 0.010). Over 75% of respondents identified decreased family and personal time, long work hours, and limited access to maternity or paternity leave as potential barriers to neurosurgery, with no differences by gender. Respondents overall saw being female and low-income as disadvantageous to pursuing neurosurgery in Nigeria. Although they universally viewed research as important in neurosurgery, 59% of respondents reported inadequate access to research opportunities; this did not vary by gender. However, 65% of female respondents reported that having a female neurosurgery mentor would increase their interest in neurosurgery (vs. 37% of males, P = 0.001). CONCLUSIONS: Nigerian medical trainees perceived the time commitment of neurosurgery as a major barrier to pursuing the specialty. Regardless of gender, they also reported low exposure to neurosurgery and inadequate access to research and mentorship opportunities. However, we found that enhanced female representation among neurosurgery mentors and improved work-life balance could increase interest in neurosurgery and help expand Nigeria's neurosurgical workforce.

Evaluation of the Glasgow Coma Scale-Pupils score for predicting inpatient mortality among patients with traumatic subdural hematoma at United States trauma centers.

OBJECTIVE: The Glasgow Coma Scale-Pupils (GCS-P) score has been suggested to better predict patient outcomes compared with GCS alone, while avoiding the need for more complex clinical models. This study aimed to compare the prognostic ability of GCS-P versus GCS in a national cohort of traumatic subdural hematoma (SDH) patients. METHODS: Patient data were obtained from the National Trauma Data Bank (2017-2019). Inclusion criteria were traumatic SDH diagnosis with available data on presenting GCS score, pupillary reactivity, and discharge disposition. Patients with severe polytrauma or nonsurvivable head injury at presentation were excluded. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of GCS-P versus GCS scores for inpatient mortality prediction were evaluated across the entire cohort, as well as in subgroups based on age and traumatic brain injury (TBI) type (blunt vs penetrating). Calibration curves were plotted based on predicted probabilities and actual outcomes. RESULTS: A total of 196,747 traumatic SDH patients met the study inclusion criteria. Sensitivity (0.707 vs 0.702), specificity (0.821 vs 0.823), and AUC (0.825 vs 0.814, p < 0.001) of GCS-P versus GCS scores for prediction of inpatient mortality were similar. Calibration curve analysis revealed that GCS scores slightly underestimated inpatient mortality risk, whereas GCS-P scores did not. In patients > 65 years of age with blunt TBI (51.9%, n = 102,148), both GCS-P and GCS scores underestimated inpatient mortality risk. In patients with penetrating TBI (2.4%, n = 4,710), the AUC of the GCS-P score was significantly higher (0.902 vs 0.851, p < 0.001). In this subgroup, both GCS-P and GCS scores underestimated inpatient mortality risk among patients with lower rates of observed mortality and overestimated risk among patients with higher rates of observed mortality. This effect was more pronounced in the GCS-P calibration curve. CONCLUSIONS: The GCS-P score provides better short-term prognostication compared with the GCS score alone among traumatic SDH patients with penetrating TBI. The GCS-P score overestimates inpatient mortality risk among penetrating TBI patients with higher rates of observed mortality. For penetrating TBI patients, which comprised 2.4% of our SDH cohort, a low GCS-P score should not justify clinical nihilism or forgoing aggressive treatment.

Exploring the impact of primary care utilization and health information exchange upon treatment patterns and clinical outcomes of glioblastoma patients.

PURPOSE: There is limited literature describing care coordination for patients with glioblastoma (GBM). We aimed to investigate the impact of primary care and electronic health information exchange (HIE) between neurosurgeons, oncologists, and primary care providers (PCP) on GBM treatment patterns, postoperative outcomes, and survival. METHODS: We identified adult GBM patients undergoing primary resection at our institution (2007-2020). HIE was defined as shared electronic medical information between PCPs, oncologists, and neurosurgeons. Multivariate logistic regression analyses were used to determine the effect of PCPs and HIE upon initiation and completion of adjuvant therapy. Kaplan-Meier and multivariate Cox regression models were used to evaluate overall survival (OS). RESULTS: Among 374 patients (mean age ± SD: 57.7 ± 13.5, 39.0% female), 81.0% had a PCP and 62.4% had electronic HIE. In multivariate analyses, having a PCP was associated with initiation (OR: 7.9, P < 0.001) and completion (OR: 4.4, P < 0.001) of 6 weeks of concomitant chemoradiation, as well as initiation (OR: 4.0, P < 0.001) and completion (OR: 3.0, P = 0.007) of 6 cycles of maintenance temozolomide thereafter. Having a PCP (median OS [95%CI]: 14.6[13.1-16.1] vs. 10.8[8.2-13.3] months, P = 0.005) and HIE (15.40[12.82-17.98] vs. 13.80[12.51-15.09] months, P = 0.029) were associated with improved OS relative to counterparts in Kaplan-Meier analysis and in multivariate Cox regression analysis (hazard ratio [HR] = 0.7, [95% CI] 0.5-1.0, P = 0.048). In multivariate analyses, chemoradiation (HR = 0.34, [95% CI] 0.2-0.7, P = 0.002) and maintenance temozolomide (HR = 0.5, 95%CI 0.3-0.8, P = 0.002) were associated with improved OS relative to counterparts. CONCLUSION: Effective care coordination between neurosurgeons, oncologists, and PCPs may offer a modifiable avenue to improve GBM outcomes.

The Socioeconomic Distressed Communities Index Predicts 90-Day Mortality Among Intracranial Tumor Patients.

BACKGROUND: Socioeconomic status (SES) is a major determinant of quality of life and outcomes. However, SES remains difficult to measure comprehensively. Distress communities index (DCI), a composite of 7 socioeconomic factors, has been increasingly recognized for its correlation with poor outcomes. As a result, the objective of the present study is to determine the predictive value of the DCI on outcomes following intracranial tumor surgery. METHODS: A single institution, retrospective review was conducted to identify adult intracranial tumor patients undergoing resection (2016-2021). Patient ZIP codes were matched to DCI and stratified by DCI quartiles (low:0-24.9, low-intermediate:25-49.9, intermediate-high:50-74.9, high:75-100). Univariate followed by multivariate regressions assessed the effects of DCI on postoperative outcomes. Receiver operating curves were generated for significant outcomes. RESULTS: A total of 2389 patients were included: 1015 patients (42.5%) resided in low distress communities, 689 (28.8%) in low-intermediate distress communities, 445 (18.6%) in intermediate-high distress communities, and 240 (10.0%) in high distress communities. On multivariate analysis, risk of fracture (adjusted odds ratio = 1.60, 95% confidence interval 1.26-2.05, P < 0.001) and 90-day mortality (adjusted odds ratio = 1.58, 95% confidence interval 1.21-2.06, P < 0.001) increased with increasing DCI quartile. Good predictive accuracy was observed for both models, with receiver operating curves of 0.746 (95% CI 0.720-0.766) for fracture and 0.743 (95% CI 0.714-0.772) for 90-day mortality. CONCLUSIONS: Intracranial tumor patients from distressed communities are at increased risk for adverse events and death in the postoperative period. DCI may be a useful, holistic measure of SES that can help risk stratifying patients and should be considered when building healthcare pathways.

The Johns Hopkins Physician-Scientist Training Program to Enhance Institutional Retention and Entry Into Academic Positions: An Evaluation of Program Effectiveness and Outcomes.

PURPOSE: The Johns Hopkins Physician-Scientist Training Program (PSTP) was implemented to overcome well-documented challenges in training and retaining physician-scientists by providing physician-scientist pathway training for residents and clinical fellows. The program's core tenets include monthly seminars, individualized feedback on project proposals, access to mentors, and institutional funding opportunities. This study evaluated the effectiveness and outcomes of the PTSP and provides a framework for replication. METHOD: A query of institutional demographic data and bibliometric variables of the PSTP participants (2017-2020) at a single academic medical center was conducted in 2021. In addition, a voluntary survey collected personal and program evaluation information. RESULTS: Of 145 PSTP scholars, 59 (41%) were women, and 41 (31%), 8 (6%), and 6 (5%) of scholars self-identified as Asian, Hispanic, and Black, respectively. Thirty-three (23%) scholars received PSTP research support or career development microgrants. Of 66 PSTP graduates, 29 (44%) remained at Johns Hopkins as clinical fellows or faculty. Of 48 PSTP graduates in a post-training position, 42 (88%) were in academia, with the majority, 29 (76%), holding the rank of assistant professor. Fifty-nine of 140 available participants responded to the survey (42% response rate). The top-cited reason for joining the PSTP was exposure to mentors and administration (50/58 respondents, 86%), followed by seeking scholarly opportunities (37/58 respondents, 64%). Most scholars intended to continue a career as a physician-scientist. CONCLUSIONS: The PSTP provides internal research support and institutional oversight. Although establishing close mentor-mentee relationships requires individualized approaches, the PSTP provided structured academic pathways that enhanced participating scholars' ability to apply for grants and jobs. The vast majority continued their careers as physician-scientists after training. In light of the national evidence of a "leaky physician-scientist pipeline," programs such as the PSTP can be critical to entry into early academic career positions and institutional retention.

Resection of an incidentally discovered spinal arachnoid web: illustrative case.

BACKGROUND: Spinal arachnoid webs (SAWs) are rare pathologies of the spinal meninges often associated with syringomyelia and the radiographic "scalpel sign." Patients can experience pain, numbness, gait disturbances, or no symptoms at all. They are typically diagnosed via magnetic resonance imaging and treated with laminectomy and excision. OBSERVATIONS: A 61-year-old male presented after a mechanical fall and had an incidentally discovered SAW on imaging. He was initially asymptomatic and was therefore conservatively managed. Several years later, however, the patient experienced new-onset back pain, paresthesia, and balance problems, with interval imaging demonstrating worsening of the edema surrounding his SAW. The patient subsequently underwent resection of the SAW, which led to significant resolution of his symptoms. LESSONS: An SAW can be asymptomatic or can manifest with a wide variety of symptoms. When this condition is incidentally discovered in asymptomatic patients, neurosurgeons should guide these patients to follow-up urgently if they develop any neurological symptoms. At that time, further imaging can be performed to determine if surgical treatment is indicated. Although SAW is rare, clinicians should be aware of the signs and symptoms, because prompt surgical intervention can significantly improve neurological symptoms.

Exploring disparities in surgical recommendations for patients with primary intramedullary spinal cord tumors: an analysis of the Surveillance, Epidemiology, and End Results database from 2000 to 2019.

OBJECTIVE: Factors that may drive recommendations for operative intervention for patients with intramedullary spinal cord tumors (ISCTs) have yet to be extensively studied. The authors investigated racial and socioeconomic disparities in the management of patients with primary spinal cord ependymomas and nonependymal gliomas, with the aim of determining the associations between socioeconomic patient characteristics, survival, and recommendations for the resection of primary ISCTs. METHODS: The Surveillance, Epidemiology, and End Results registry was queried to identify all patients > 18 years of age with ISCTs diagnosed between 2000 and 2019. Univariable and multivariable logistic regression analyses were used to calculate odds ratios for variables associated with receiving a surgical recommendation. Log-rank tests and multivariable Cox proportional hazards models were used to investigate overall survival (OS) and disease-specific survival (DSS). RESULTS: The authors identified 2325 patients (mean age 49 [SD 16] years; 48.8% female; 67.4% non-Hispanic White, 7.8% non-Hispanic Black, 16.2% Hispanic, 6.5% Asian/Pacific Islander, 0.6% Native American; 56.7% married; 64.4% with household income < $75,000; 73.8% with spinal ependymoma; and 26.2% with nonependymal spinal glioma). Eighty-seven percent of patients received a surgical recommendation. In multivariable models, marriage was associated with higher odds of receiving a surgical recommendation for ependymomas (OR 1.80, p = 0.005). In multivariable models for nonependymal spinal gliomas, older age (OR 0.98, p = 0.001) and increased number of tumors (OR 0.62, p = 0.015) were associated with decreased odds of receiving surgical recommendations. Among ependymomas, marriage (HR 0.59, p = 0.001), younger age (HR 0.93, p < 0.001), female sex (HR 0.43, p = 0.006), and decreased number of tumors (HR 0.56, p < 0.001) were associated with improved OS. Among nonependymal spinal gliomas, median household income ≥ $75,000 (HR 0.69, p = 0.020) and younger age (HR 0.98, p < 0.001) were associated with improved DSS, while Black race (HR 4.65, p = 0.027) and older age (HR 1.05, p < 0.001) were associated with worse OS. CONCLUSIONS: In patients with spinal ependymomas and nonependymal spinal gliomas, recommendations for surgery appear to be unaffected by patient sex, race, or income. Survival disparities appear to exist among unmarried, male, Black, and lower-income cohorts. Continued initiatives to identify drivers of disparities while improving health equity in this patient population are needed.

Awake Versus Asleep Craniotomy for Patients With Eloquent Glioma: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Awake vs asleep craniotomy for patients with eloquent glioma is debatable. This systematic review and meta-analysis sought to compare awake vs asleep craniotomy for the resection of gliomas in the eloquent regions. METHODS: MEDLINE and PubMed were searched from inception to December 13, 2022. Primary outcomes were the extent of resection (EOR), overall survival (month), progression-free survival (month), and rates of neurological deficit, Karnofsky performance score, and seizure freedom at the 3-month follow-up. Secondary outcomes were duration of operation (minute) and length of hospital stay (LOS) (day). RESULTS: Fifteen studies yielded 2032 patients, from which 800 (39.4%) and 1232 (60.6%) underwent awake and asleep craniotomy, respectively. The meta-analysis concluded that the awake group had greater EOR (mean difference [MD] = MD = 8.52 [4.28, 12.76], P < .00001), overall survival (MD = 2.86 months [1.35, 4.37], P = .0002), progression-free survival (MD = 5.69 months [0.75, 10.64], P = .02), 3-month postoperative Karnofsky performance score (MD = 13.59 [11.08, 16.09], P < .00001), and 3-month postoperative seizure freedom (odds ratio = 8.72 [3.39, 22.39], P < .00001). Furthermore, the awake group had lower 3-month postoperative neurological deficit (odds ratio = 0.47 [0.28, 0.78], P = .004) and shorter LOS (MD = -2.99 days [-5.09, -0.88], P = .005). In addition, the duration of operation was similar between the groups (MD = 37.88 minutes [-34.09, 109.86], P = .30). CONCLUSION: Awake craniotomy for gliomas in the eloquent regions benefits EOR, survival, postoperative neurofunctional outcomes, and LOS. When feasible, the authors recommend awake craniotomy for surgical resection of gliomas in the eloquent regions.

Craniotomy versus craniectomy for traumatic acute subdural hematoma-coarsened exact matched analysis of outcomes.

BACKGROUND AND OBJECTIVES: Acute subdural hematoma (aSDH) after traumatic brain injury frequently requires emergent craniotomy (CO) or decompressive craniectomy (DC). We sought to determine the variables associated with either surgical approach and to compare outcomes between matched patients. METHODS: A multi-center retrospective review was used to identify traumatic aSDH patients who underwent CO or DC. Patient variables independently associated with surgical approach were used for coarsened exact matching.Multivariate logistic regression and multivariate Cox proportional-hazards regression wereconducted on matched patients to determine independent predictors of mortality. RESULTS: Seventy-six patients underwent CO and sixty-two underwent DC for aSDH evacuation. DC patients were21.4 years younger (P < 0.001), more likely to be male (80.6 % vs 60.5 %,P = 0.011), and present with GCS ≤ 8 (64.5 % vs 36.8 %,P = 0.001). Age (P < 0.001), epidural hematoma (P = 0.01), skull fracture (P = 0.001), and cisternal effacement (P = 0.02) were independently associated with surgical approach. After coarsened exact matching, DC (P = 0.008), older age (P = 0.007), male sex (P = 0.04), and intraventricular hemorrhage (P = 0.02), were independently associated with inpatient mortality. Multivariate Cox proportional-hazards regression demonstrated that DC was independently associated with mortality at 90-days (P = 0.001) and 1-year post-operation (P = 0.003). CONCLUSION: aSDH patients who receive surgical evacuation via DC as opposed to CO are younger, more likely to be male, and have worse clinical exam. After controlling for patient differences via coarsened exact matching, DC is independently associated with mortality.

Impact of Antithrombotic Medications and Reversal Strategies on the Surgical Management and Outcomes of Traumatic Acute Subdural Hematoma.

OBJECTIVE: Careful hematologic management is required in surgical patients with traumatic acute subdural hematoma (aSDH) taking antithrombotic medications. We sought to compare outcomes between patients with aSDH taking antithrombotic medications at admission who received antithrombotic reversal with patients with aSDH not taking antithrombotics. METHODS: Retrospective review identified patients with traumatic aSDH requiring surgical evacuation. The cohort was divided based on antithrombotic use and whether pharmacologic reversal agents or platelet transfusions were administered. A 3-way comparison of outcomes was performed between patients taking anticoagulants who received pharmacologic reversal, patients taking antiplatelets who received platelet transfusion, and patients not taking antithrombotics. Multivariable regressions, adjusted for injury severity, further investigated associations with outcomes. RESULTS: Of 138 patients who met inclusion criteria, 13.0% (n = 18) reported taking anticoagulants, 16.7% (n = 23) reported taking antiplatelets, and 3.6% (n = 5) reported taking both. Patients taking antiplatelets who received platelet transfusion had longer intraoperative times (P = 0.040) and higher rates of palliative care consultations (P = 0.046) compared with patients taking anticoagulants who received pharmacologic reversal and patients not taking antithrombotics. Across groups, no significant differences were found in frequency of in-hospital intracranial hemorrhage and venous thromboembolism, length of hospital stay, rate of inpatient mortality, or follow-up health status. In multivariable analysis, intraoperative time remained longest for the antiplatelets with platelet transfusion group. Other outcomes were not associated with patient group. CONCLUSIONS: Among surgical patients with traumatic aSDH, those taking antiplatelet medications who receive platelet transfusions experience longer intraoperative procedure times and higher rates of palliative care consultation. Comparable outcomes were observed between patients receiving antithrombotic reversal and patients not taking antithrombotics.

The Role of γδ T-Lymphocytes in Glioblastoma: Current Trends and Future Directions.

Cell-based immunotherapy for glioblastoma (GBM) encounters major challenges due to the infiltration-resistant and immunosuppressive tumor microenvironment (TME). γδ T cells, unconventional T cells expressing the characteristic γδ T cell receptor, have demonstrated promise in overcoming these challenges, suggesting great immunotherapeutic potential. This review presents the role of γδ T cells in GBM and proposes several research avenues for future studies. Using the PubMed, ScienceDirect, and JSTOR databases, we performed a review of the literature studying the biology of γδ T cells and their role in GBM treatment. We identified 15 studies focused on γδ T cells in human GBM. Infiltrative γδ T cells can incite antitumor immune responses in certain TMEs, though rapid tumor progression and TME hypoxia may impact the extent of tumor suppression. In the studies, available findings have shown both the potential for robust antitumor activity and the risk of protumor activity. While γδ T cells have potential as a therapeutic agent against GBM, the technical challenges of extracting, isolating, and expanding γδ T cells, and the activation of antitumoral versus protumoral cascades, remain barriers to their application. Overcoming these limitations may transform γδ T cells into a promising immunotherapy in GBM.

Reduction of cervicothoracic spondyloptosis in an ambulatory patient: when traction fails.

INTRODUCTION: Cervical spondyloptosis is a rare complication of high-energy trauma which often results in significant patient morbidity and mortality. The authors present a case of spondyloptosis of C7 over T1 with minimal radicular symptoms and otherwise complete spinal cord sparing. This case highlights the surgical challenges faced with cervical spondyloptosis and the techniques used when traction fails. CASE PRESENTATION: A 21-year-old man with no significant past medical history presented after a high-speed motor vehicle collision with cervicothoracic pain and mild hand grip weakness in addition to numbness of the fourth and fifth digits bilaterally (American Spinal Injury Association Impairment Scale Grade D). Computed tomography imaging revealed spondyloptosis of C7 over T1, a fracture of the C2 vertebral body, and a burst fracture of C3. To relieve spinal cord compression and restore sagittal realignment, closed reduction was attempted, however this resulted in perching of the bilateral C7-T1 facets, leading to an open posterior approach. The patient underwent C7 laminectomy, bilateral C7-T1 facetectomy, and manual reduction using a Mayfield skull clamp followed by C2-T3 fixation. Postoperatively, pain was diminished, sensory disturbances were resolved and the patient was otherwise neurologically stable. DISCUSSION: There is a role for closed traction for reduction of cervical spondyloptosis, however, its role is debated especially when the patient is predominately neurologically intact. In this setting, the spine surgeon may be required to change traction and operative strategies in order to minimize potentially harmful manipulation while restoring sagittal realignment and stabilizing the spine for preservation of neurological function.

Management and Molecular Characterization of Intraventricular Glioblastoma: A Single-Institution Case Series.

While the central nervous system (CNS) tumor classification has increasingly incorporated molecular parameters, there is a paucity of literature reporting molecular alterations found in intraventricular glioblastoma (IVGBM), which are rare. We present a case series of nine IVGBMs, including molecular alterations found in standardized next-generation sequencing (NGS). We queried the clinical charts, operative notes, pathology reports, and radiographic images of nine patients with histologically confirmed IVGBM treated at our institution (1995-2021). Routine NGS was performed on resected tumor tissue of two patients. In this retrospective case series of nine patients (22% female, median (range) age: 64.3 (36-85) years), the most common tumor locations were the atrium of the right lateral ventricle (33%) and the septum pellucidum (33%). Five patients had preoperative hydrocephalus, which was managed with intraoperative external ventricular drains in three patients and ventriculoperitoneal shunts in one patient. Hydrocephalus was managed with subtotal resection of a fourth ventricular IVGBM in one patient. The most common surgical approach was transcortical intraventricular (56%). Gross total resection was achieved in two patients, subtotal resection was achieved in six patients, and one patient received a biopsy only. Immunohistochemistry for IDH1 R132H mutant protein was performed in four cases and was negative in all four. Genetic alterations common in glioblastoma, IDH-wildtype, were seen in two cases with available NGS data, including EGFR gene amplification, TERT promoter mutation, PTEN mutation, trisomy of chromosome 7, and monosomy of chromosome 10. Following surgical resection, four patients received adjuvant chemoradiation. Median survival among our cohort was 4.7 months (IQR: 0.9-5.8 months). Management of IVGBM is particularly challenging due to their anatomical location, presentation with obstructive hydrocephalus, and fast growth, necessitating prompt intervention. Additional studies are needed to better understand the genetic landscape of IVGBM compared to parenchymal glioblastoma and may further elucidate the unique pathophysiology of these rare tumors.

Epidemiology and survival outcomes of synchronous and metachronous brain metastases: a retrospective population-based study.

OBJECTIVE: Brain metastases (BMs) are the most common CNS tumors, yet their prevalence is difficult to determine. Most studies only report synchronous metastases, which make up a fraction of all BMs. The authors report the incidence and prognosis of patients with synchronous and metachronous BMs over a decade. METHODS: Study data were obtained from the TriNetX Research Network. Patients were included if they had a primary cancer diagnosis and a BM diagnosis, with primary cancer occurring between January 1, 2013, and January 1, 2023. Metachronous BM was defined as BM diagnosed more than 2 months after the primary cancer. Cohorts were balanced by propensity score matching for age, extracranial metastasis, and antineoplastic or radiation therapy. Kaplan-Meier plots were used to evaluate survival differences between synchronous and metachronous BMs and associations with clinical conditions. A log-rank test was used to evaluate BM-free survival for metachronous BM and overall survival (OS) for all BMs. Hazard ratios and 95% CIs were calculated. RESULTS: Of the 11,497,663 patients with 15 primary cancers identified, 300,863 (2.6%) developed BMs. BMs most commonly arose from lung and breast cancers and melanoma. Of all BMs, 113,827 (37.8%) presented synchronously and 187,036 (62.2%) presented metachronously. Lung and bronchial cancer had the highest metastasis rate (11.0%) and the highest synchronous presentation (51.0%). For metachronous presentations, the time from primary diagnosis to metastasis ranged from 1.3 to 2.5 years, averaging 1.8 years. Metachronous BM diagnosis was associated with longer survival over synchronous BM from primary diagnosis (11.54 vs 37.41 months, p < 0.0001), but shorter survival than extracranial metastases without BM (38.75 vs 69.18 months, p < 0.0001). Antineoplastic therapy prior to BM was associated with improved BM-free survival (4.46 vs 17.80 months, p < 0.0001) and OS (25.15 vs 42.26 months, p < 0.0001). Radiotherapy showed a similar effect that was statistically significant but modest for BM-free survival (5.25 vs 11.44 months, p < 0.0001) and OS (30.13 vs 32.82 months, p < 0.0001). CONCLUSIONS: The majority of BMs present metachronously and arise within 2 years of primary cancer diagnosis. The substantial rate of BMs presenting within 6 months of primary cancer, especially liver, lung, and pancreatic cancer, may guide future recommendations on intracranial staging. Antineoplastic therapy prior to the development of BM may prolong the time before metastasis and improve survival. Further characterization of this population can better inform screening, prevention, and treatment efforts.

Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid.

It is often challenging to distinguish cancerous from non-cancerous lesions in the brain using conventional diagnostic approaches. We introduce an analytic technique called Real-CSF (repetitive element aneuploidy sequencing in CSF) to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) are PCR amplified with a single primer pair, and the PCR products are evaluated by next-generation sequencing. Real-CSF assesses genome-wide copy-number alterations as well as focal amplifications of selected oncogenes. Real-CSF was applied to 280 CSF samples and correctly identified 67% of 184 cancerous and 96% of 96 non-cancerous brain lesions. CSF analysis was considerably more sensitive than standard-of-care cytology and plasma cell-free DNA analysis in the same patients. Real-CSF therefore has the capacity to be used in combination with other clinical, radiologic, and laboratory-based data to inform the diagnosis and management of patients with suspected cancers of the brain.

ME3BP-7 is a targeted cytotoxic agent that rapidly kills pancreatic cancer cells expressing high levels of monocarboxylate transporter MCT1.

Nearly 30% of Pancreatic ductal adenocarcinoma (PDAC)s exhibit a marked overexpression of Monocarboxylate Transporter 1 (MCT1) offering a unique opportunity for therapy. However, biochemical inhibitors of MCT1 have proven unsuccessful in clinical trials. In this study we present an alternative approach using 3-Bromopyruvate (3BP) to target MCT1 overexpressing PDACs. 3BP is a cytotoxic agent that is known to be transported into cells via MCT1, but its clinical usefulness has been hampered by difficulties in delivering the drug systemically. We describe here a novel microencapsulated formulation of 3BP (ME3BP-7), that is effective against a variety of PDAC cells in vitro and remains stable in serum. Furthermore, systemically administered ME3BP-7 significantly reduces pancreatic cancer growth and metastatic spread in multiple orthotopic models of pancreatic cancer with manageable toxicity. ME3BP-7 is, therefore, a prototype of a promising new drug, in which the targeting moiety and the cytotoxic moiety are both contained within the same single small molecule. One Sentence Summary: ME3BP-7 is a novel formulation of 3BP that resists serum degradation and rapidly kills pancreatic cancer cells expressing high levels of MCT1 with tolerable toxicity in mice.

Surgery or Endovascular Treatment in Patients with Anterior Communicating Artery Aneurysm: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Although randomized controlled trials have compared surgery versus endovascular treatment for intracranial aneurysms, the literature is sparse in terms of subgroup analysis for anterior communicating artery (ACoA) aneurysm management. This systematic review and meta-analysis sought to compare surgical versus endovascular treatment for ACoA aneurysms. METHODS: Medline, PubMed, and Embase were searched from inception to December 12, 2022. Primary outcomes were post-treatment modified Rankin Scale (mRS) >2 and mortality. Secondary outcomes were aneurysm obliteration, retreatment and recurrence, rebleeding, technical failure, vessel rupture, aneurysmal subarachnoid hemorrhage-related hydrocephalus, symptomatic vasospasm, and stroke. RESULTS: Eighteen studies yielded 2368 patients, from which 1196 (50.5%) and 1172 (49.4%) patients underwent surgery and endovascular treatment, respectively. The odds ratio (OR) of mortality was similar in total (OR = 0.92 [0.63-1.37], P = 0.69), ruptured (OR = 0.92 [0.62-1.36], P = 0.66), and unruptured cohorts (OR = 1.58 [0.06-39.60], P = 0.78). The OR of mRS > 2 was similar in total (OR = 0.75 [0.50-1.13], P = 0.17), ruptured (OR = 0.77 [0.49-1.20], P = 0.25), and unruptured cohorts (OR = 0.64 [0.21-1.96], P = 0.44). The OR of obliteration was higher with surgery in the total (OR = 2.52 [1.49-4.27], P = 0.0008) and ruptured cohorts (OR = 2.61 [1.33-5.10], P = 0.005) and unruptured group (OR = 3.46 [1.30-9.20], P = 0.01). The OR of retreatment was lower with surgery in the total (OR = 0.37 [0.17-0.76], P = 0.007) and ruptured cohorts (OR = 0.31 [0.11-0.89], P = 0.03), thought it was similar in the unruptured group (OR = 0.51 [0.08-3.03], P = 0.46). The OR of recurrence was lower with surgery in the total (OR = 0.22 [0.10, 0.47], P = 0.0001), ruptured (OR = 0.16 [0.03, 0.90], P = 0.04), and mixed (un) ruptured cohorts (OR = 0.22 [0.09-0.53], P = 0.0009). The OR of rebleeding in ruptured group was similar (OR = 0.66 [0.29-1.52], P = 0.33). The ORs of other outcomes were similar. CONCLUSIONS: ACoA aneurysms may be safely treated with either surgery or endovascular treatment, although microsurgical clipping demonstrates higher obliteration rates and lower rates of retreatment and recurrence.

The Ribbon Sign as a Radiological Indicator of Intramedullary Spinal Cord Subependymomas.

OBJECTIVE: Intramedullary spinal cord (IMSC) subependymomas are rare World Health Organization grade 1 ependymal tumors. The potential presence of functional neural tissue within the tumor and poorly demarcated planes presents a risk to resection. Anticipating a subependymoma on preoperative imaging can inform surgical decision-making and improve patient counseling. Here, we present our experience recognizing IMSC subependymomas on preoperative magnetic resonance imaging (MRI) based on a distinctive characteristic termed the "ribbon sign." METHODS: We retrospectively reviewed preoperative MRIs of patients presenting with IMSC tumors at a large tertiary academic institution between April 2005 and January 2022. The diagnosis was confirmed histologically. The "ribbon sign" was defined as a ribbon-like structure of T2 isointense spinal cord tissue interwoven between regions of T2 hyperintense tumor. The ribbon sign was confirmed by an expert neuroradiologist. RESULTS: MRIs from 151 patients were reviewed, including 10 patients with IMSC subependymomas. The ribbon sign was demonstrated on 9 (90%) patients with histologically proven subependymomas. Other tumor types did not display the ribbon sign. CONCLUSION: The ribbon sign is a potentially distinctive imaging feature of IMSC subependymomas and indicates the presence of spinal cord tissue between eccentrically located tumors. Recognition of the ribbon sign should prompt clinicians to consider a diagnosis of subependymoma, aiding the neurosurgeon in planning the surgical approach and adjusting the surgical outcome expectation. Consequently, the risks and benefits of gross-versus subtotal resection for palliative debulking should be carefully considered and discussed with patients.