An Interpretable Machine Learning Approach to Predict Survival Outcomes in Spinal and Sacropelvic Chordomas.

STUDY DESIGN: Retrospective, population-based cohort study. OBJECTIVE: This study aimed to develop machine learning (ML) models to predict five-year and 10-year mortality in spinal and sacropelvic chordoma patients and integrate them into a web application for enhanced prognostication. SUMMARY OF BACKGROUND DATA: Past research has uncovered factors influencing survival in spinal chordoma patients. While identifying individual predictors is important, personalized survival predictions are equally vital. Though prior efforts have resulted in nomograms aiming to serve this purpose, they cannot capture complex interactions within data and rely on statistical assumptions that may not fit real-world data. METHODS: Adult spinal and sacropelvic chordoma patients were identified from the National Cancer Database. Sociodemographic, clinicopathologic, diagnostic, and treatment-related variables were utilized as predictive features. Five supervised ML algorithms (TabPFN, CatBoost, XGBoost, LightGBM, and Random Forest) were implemented to predict mortality at five and 10 years postdiagnosis. Model performance was primarily evaluated using the area under the receiver operating characteristic (AUROC). SHapley Additive exPlanations (SHAP) values and partial dependence plots provided feature importance and interpretability. The top models were integrated into a web application. RESULTS: From the NCDB, 1206 adult patients diagnosed with histologically confirmed spinal and sacropelvic chordomas were retrieved for the five-year mortality outcome [423 (35.1%) with five-year mortality] and 801 patients for the 10-year mortality outcome [588 (73.4%) with 10-year mortality]. Top-performing models for both of the outcomes were the models created with the CatBoost algorithm. The CatBoost model for five-year mortality predictions displayed a mean AUROC of 0.801, and the CatBoost model predicting 10-year mortality yielded a mean AUROC of 0.814. CONCLUSIONS: This study developed ML models that can accurately predict five-year to 10-year survival probabilities in spinal chordoma patients. Integrating these interpretable, personalized prognostic models into a web application provides quantitative survival estimates for a given patient. The local interpretability enables transparency into how predictions are influenced. Further external validation is warranted to support generalizability and clinical utility.

Intraspinal cervicothoracic junction chondrosarcoma: illustrative case.

BACKGROUND: Chondrosarcoma is an uncommon spinal tumor that can present as an extraskeletal mass. Rarely, these tumors present as dumbbell tumors through the neural foramina, mimicking schwannomas or neurofibromas. OBSERVATIONS: A 46-year-old female presented with 2 years of worsening right-arm radiculopathy. Magnetic resonance imaging of the thoracic spine revealed a peripherally enhancing extramedullary mass through the right T1 foramen and compressing the spinal cord. Computed tomography showed the mass to be partially calcified. She underwent C7-T2 laminectomy and C6-T3 posterior instrumented fusion with gross-total resection of an extradural mass. Pathology revealed a grade I chondrosarcoma. Her symptoms improved postoperatively, with some residual right-arm radicular pain. LESSONS: Intraspinal extradural dumbbell conventional chondrosarcoma is rare, with only 9 cases, including ours, reported. Patient ages range from 16 to 72 years old, and male sex is more common in these cases. The most common location is the thoracic spine, and our case is the only reported one in the cervicothoracic junction. These tumors often mimic schwannomas on imaging, but chondrosarcoma should remain in the differential diagnosis, because management of these tumors differs. Chondrosarcoma may benefit from more aggressive resection, including en bloc resection, and may require adjuvant radiotherapy.

Ultra-Early (<5 Hours) Decompression for Thoracolumbar Spinal Cord Injury: A Case Series.

Early surgical decompression within 24 hours for traumatic spinal cord injury (SCI) is associated with improved neurological recovery. However, the ideal timing of decompression is still up for debate. The objective of this study was to utilize our retrospective single-institution series of ultra-early (<5 hours) decompression to determine if ultra-early decompression led to improved neurological outcomes and was a feasible target over previously defined early decompression targets. Retrospective data on patients with SCI who underwent ultra-early (<5 hours) decompression at a level one metropolitan trauma center were extracted and collected from 2015-2018. American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade improvement was the primary outcome, with ASIA Motor score improvement and complication rate as secondary outcomes. Four individuals met the criteria for inclusion in this case series. All four suffered thoracolumbar SCI. All patients improved neurologically by AIS grade, and there were no complications directly related to ultra-early surgery. Given the small sample size, there was no statistically significant difference in outcomes compared to a control group who underwent early (5-24 hour) decompression in the same period. Ultra-early decompression is a feasible and safe target for thoracolumbar SCI and may lead to improved neurological outcomes without increased risk of complications. This case series can help create the foundation for future, larger studies that may definitively show the benefit of ultra-early decompression.

Development and internal validation of machine learning models for personalized survival predictions in spinal cord glioma patients.

BACKGROUND CONTEXT: Numerous factors have been associated with the survival outcomes in patients with spinal cord gliomas (SCG). Recognizing these specific determinants is crucial, yet it is also vital to establish a reliable and precise prognostic model for estimating individual survival outcomes. OBJECTIVE: The objectives of this study are twofold: first, to create an array of interpretable machine learning (ML) models developed for predicting survival outcomes among SCG patients; and second, to integrate these models into an easily navigable online calculator to showcase their prospective clinical applicability. STUDY DESIGN: This was a retrospective, population-based cohort study aiming to predict the outcomes of interest, which were binary categorical variables, in SCG patients with ML models. PATIENT SAMPLE: The National Cancer Database (NCDB) was utilized to identify adults aged 18 years or older who were diagnosed with histologically confirmed SCGs between 2010 and 2019. OUTCOME MEASURES: The outcomes of interest were survival outcomes at three specific time points post-diagnosis: 1, 3, and 5 years. These outcomes were formed by combining the "Vital Status" and "Last Contact or Death (Months from Diagnosis)" variables. Model performance was evaluated visually and numerically. The visual evaluation utilized receiver operating characteristic (ROC) curves, precision-recall curves (PRCs), and calibration curves. The numerical evaluation involved metrics such as sensitivity, specificity, accuracy, area under the PRC (AUPRC), area under the ROC curve (AUROC), and Brier Score. METHODS: We employed five ML algorithms-TabPFN, CatBoost, XGBoost, LightGBM, and Random Forest-along with the Optuna library for hyperparameter optimization. The models that yielded the highest AUROC values were chosen for integration into the online calculator. To enhance the explicability of our models, we utilized SHapley Additive exPlanations (SHAP) for assessing the relative significance of predictor variables and incorporated partial dependence plots (PDPs) to delineate the influence of singular variables on the predictions made by the top performing models. RESULTS: For the 1-year survival analysis, 4,913 patients [5.6% with 1-year mortality]; for the 3-year survival analysis, 4,027 patients (11.5% with 3-year mortality]; and for the 5-year survival analysis, 2,854 patients (20.4% with 5-year mortality) were included. The top models achieved AUROCs of 0.938 for 1-year mortality (TabPFN), 0.907 for 3-year mortality (LightGBM), and 0.902 for 5-year mortality (Random Forest). Global SHAP analyses across survival outcomes at different time points identified histology, tumor grade, age, surgery, radiotherapy, and tumor size as the most significant predictor variables for the top-performing models. CONCLUSIONS: This study demonstrates ML techniques can develop highly accurate prognostic models for SCG patients with excellent discriminatory ability. The interactive online calculator provides a tool for assessment by physicians (https://huggingface.co/spaces/MSHS-Neurosurgery-Research/NCDB-SCG). Local interpretability informs prediction influences for a given individual. External validation across diverse datasets could further substantiate potential utility and generalizability. This robust, interpretable methodology aligns with the goals of precision medicine, establishing a foundation for continued research leveraging ML's predictive power to enhance patient counseling.

From Text to Insight: A Natural Language Processing-Based Analysis of Topics and Trends in Neurosurgery.

BACKGROUND AND OBJECTIVES: Neurosurgical research is a rapidly evolving field, with new research topics emerging continually. To provide a clearer understanding of the evolving research landscape, our study aimed to identify and analyze the prevalent research topics and trends in Neurosurgery. METHODS: We used BERTopic, an advanced natural language processing-based topic modeling approach, to analyze papers published in the journal Neurosurgery . Using this method, topics were identified based on unique sets of keywords that encapsulated the core themes of each article. Linear regression models were then trained on the topic probabilities to identify trends over time, allowing us to identify "hot" (growing in prominence) and "cold" (decreasing in prominence) topics. We also performed a focused analysis of the trends in the current decade. RESULTS: Our analysis led to the categorization of 12 438 documents into 49 distinct topics. The topics covered a wide range of themes, with the most commonly identified topics being "Spinal Neurosurgery" and "Treatment of Cerebral Ischemia." The hottest topics of the current decade were "Peripheral Nerve Surgery," "Unruptured Aneurysms," and "Endovascular Treatments" while the cold topics were "Chiari Malformations," "Thromboembolism Prophylaxis," and "Infections." CONCLUSION: Our study underscores the dynamic nature of neurosurgical research and the evolving focus of the field. The insights derived from the analysis can guide future research directions, inform policy decisions, and identify emerging areas of interest. The use of natural language processing in synthesizing and analyzing large volumes of academic literature demonstrates the potential of advanced analytical techniques in understanding the research landscape, paving the way for similar analyses across other medical disciplines.

Ultra-early (≤8 hours) surgery for thoracolumbar spinal cord injuries: A systematic review and meta-analysis.

Background: The impact of the timing of surgery on neurological recovery in thoracolumbar spinal cord injuries (tSCI) is still a subject of discussion. Accumulating evidence is supporting early decompression (<24 hours) following tSCI. However, the potential advantages of earlier decompression remain uncertain. This systematic review and meta-analysis summarize and analyze the current evidence on the effectiveness of ultra-early decompression surgery on clinical outcomes following tSCI. Methods: A search was conducted in the electronic databases Medline, Embase, Scopus, and Web of Science from their inception until May 2022 for human studies. Groups were stratified into ultra-early (surgery within 8 hours of injury) vs control group operated >8 hours of injury. The authors included the study data from their institutional case series of thoracolumbar spinal cord injury from 2015 to 2018. An arm-based meta-analysis was performed on all studies using the R Studio. For studies that qualified, a contrast-based meta-analysis was also performed with a standardized mean difference (SMD). Outcomes were reported as effect size, treatment effect, and effect difference, all with 95% confidence intervals (CI). Results: Of the 133 patients, 74.4% patients were male. 76 (57.1%) underwent decompression ≤8 hours, while 57 (42.9%) underwent decompression >8 hours from injury. Quantitative analysis using the SMD model showed a significant difference in mean AIS improvement in the ultra-early group (Effect size 1.15 [0.62-1.67], p<.0001). On arm-based meta-analysis, a statistically significant treatment effect was found for the ultra-early arm (1.25 [0.91-1.67]), while > 8-hour arm did not show significance (0.30 [-0.08-0.71]). There was a statistically significant effect difference between the two arms (0.96 [0.49-1.48]). Conclusions: This study observed a significant improvement in the mean AIS score in patients undergoing decompression within 8 hours of tSCI. Given the scant literature regarding ultra-early decompression of tSCI, this study solidifies the need to further explore the role of early interventions for tSCIs to improve patient outcomes.

Da Vinci Meets Globus Excelsius GPS: A Totally Robotic Minimally Invasive Anterior and Posterior Lumbar Fusion.

BACKGROUND: Minimally invasive approaches to the spine via anterior and posterior approaches have been increasing in popularity, culminating in the development of robot-assisted spinal fusions. The da Vinci surgical robot has been used for anterior lumbar interbody fusion (ALIF), with promising results. Similarly, multiple spinal robots have been developed to assist placement of posterior pedicle screws. However, no previous cases have reported on using robots for both anterior and posterior fixation in a single surgery. We present a technical note on the first reported case of a totally robotic minimally invasive anterior and posterior lumbar fusion and instrumentation. METHODS: A 65-year-old man with chronic low back pain and left greater than right lower extremity radiculopathy was found to have grade 1 spondylolisthesis at L5/S1 that worsened on standing upright. He underwent ALIF using a da Vinci robotic approach, followed by percutaneous posterior instrumented fusion with the Globus Excelsius GPS robot. RESULTS: The patient did well postoperatively, with improvement of back and leg pain at 3 months follow-up. Radiography confirmed appropriate placement of the interbody cage and pedicle screws. CONCLUSIONS: All-robotic placement of both ALIF and posterior lumbar pedicle fixation may be safe, feasible, and efficacious.

Third Ventricular Subependymomas: Clinical Features and Outcomes Over Two Decades.

BACKGROUND: Subependymomas are uncommon, benign slow-growing neoplasms of the central nervous system preferentially arising within the fourth and lateral ventricles. Third ventricle involvement has been described rarely. The aim of this study is to provide the first systematic review of third ventricular subependymomas (TVSE) by analyzing all reported cases over 2 decades and describing a case example. METHODS: MEDLINE and Embase databases were searched for the 20 years ending January 1, 2022, using relevant MeSH and non-MeSH terms, including "subependymoma" and "third ventricle." Methodology followed PRISMA guidelines. RESULTS: Of 804 identified studies, 131 met inclusion eligibility. The literature yielded 17 patients with TVSE plus our example (18 total). Of these patients, 83% (15/18) presented in adulthood (average age, 42 ± 19 years), of whom 73% were women. The pediatric cohort age was 5 ± 1 years, 67% (4/6) of whom were girls. The most common presenting symptom in both cohorts was headache (80%), followed by memory disturbances and vomitus. In adults, symptomatic tumors were approached by open craniotomy in all but 1 case, most using a transcallosal approach. Gross total resection was obtained in 73%. A ventriculoperitoneal shunt was inserted in 2/15 adult and 4/6 pediatric patients. Overall, both cohorts showed symptomatic improvement without disease recurrence. One patient died perioperatively. CONCLUSIONS: Subependymomas should be considered in the differential diagnosis of third ventricular tumors. The clinical presentation of TVSE mainly parallels hydrocephalus symptoms and, hence, awareness is of vital importance for timely treatment. The surgical goal should be gross total resection, which can be curative and offers greatest clinical improvement across the population.

Brainstem Hemorrhage Following Lumbar Drain for Post-traumatic Hydrocephalus.

Post-traumatic hydrocephalus is common after traumatic brain injury (TBI), particularly following decompressive craniectomy. Cerebrospinal fluid (CSF) removal by lumbar drain (LD) aids in the workup of post-traumatic hydrocephalus and serves as a bridge to definitive CSF diversion. Hemorrhagic complications following LD are rare but can include intracranial hemorrhage. We present a case of fatal brainstem hemorrhage following LD in a patient three months after craniectomy. A 32-year-old male presented with severe TBI and an acute subdural hematoma. He underwent emergent decompressive craniectomy and hematoma evacuation. The next day, he required ventriculostomy for elevated intracranial pressure (ICP), which was able to be successfully removed. Three months after the injury, the patient's neurological exam declined, and computed tomography (CT) findings were consistent with communicating hydrocephalus. An LD was placed with 15 mL of CSF and drained every two hours. Five days after LD placement, the CSF became blood-tinged, and a repeat head CT demonstrated an acute brainstem hemorrhage. The patient ultimately expired. Given the prevalence of post-traumatic hydrocephalus and the frequent use of CSF diversion in the management of this condition, it is important for neurosurgeons to remain cognizant of the potential risk for catastrophic brainstem hemorrhage following LD in decompressive craniectomy patients.

Resolution and Re-ossification of Orbital-Wall Langerhans Cell Histiocytosis Following Stereotactic Needle Biopsy.

Introduction Langerhans cell histiocytosis (LCH) is a rare disease that encompasses a spectrum of clinical syndromes. It is characterized by the proliferation and infiltration of white blood cells into organs or organ systems. Reports of management of these lesions have included biopsy, resection, curettage, radiation, and/or chemotherapy. Case Presentation A 40-year-old man presented with a history of right proptosis and retro-orbital pain and was found to have a lytic mass involving the greater wing of the sphenoid extending into the right orbit. A stereotactic needle biopsy using neuronavigation demonstrated this to be LCH. After no further treatment, the mass spontaneously resolved, with virtual normalization of the orbital magnetic resonance imaging at 10 months following the needle biopsy. The bony defect of the temporal bone caused by the mass also re-ossified following the needle biopsy. Discussion This report highlights the potential for an isolated LCH lesion to regress after simple needle biopsy, an outcome only rarely reported previously. Thus, expectant management of such lesions following biopsy or initial debridement should be considered prior to proceeding with additional treatment.

Clinical Considerations and Outcomes for Spine Surgery Patients with a History of Transplant: A Systematic Scoping Review Protocol.

Spine surgery patients with a history of organ transplantation are a complex population due to their unique anesthetic considerations, immunologic profiles, drug interactions, and potential organ dysfunction. It is common for these patients to develop neck/back pain and pathology that warrants surgical intervention. However, there is a relative dearth of literature examining their outcomes and clinical considerations. The purpose of this protocol is to investigate their clinical outcomes following spine surgery and medical management. We perform a systematic literature search using PRISMA-ScR guidelines to include case reports, cohort studies, and retrospective analyses. The search terms include kidney, liver, heart, pancreas, lung, and bone marrow for transplants of interest and contain an extensive list of terms covering spine surgery. The search is conducted using Medline, Embase, and the Cochrane Central Register of Controlled Trials. A thorough examination of titles and abstracts is performed followed by data extraction. The data points include patient demographics, past medical history, spine procedural information, and clinical outcomes. This systematic review will aid clinicians in identifying demographics, medical management, and clinical outcomes for spine surgery patients with a previous organ transplant. These findings will highlight the gaps in the knowledge of this complex population and stimulate further research.

Seventy-five years of neurosurgery residency training at The Mount Sinai Hospital.

The Department of Neurosurgery's residency program at The Mount Sinai Hospital was founded in 1946. The department has its origins in 1914 as a division of general surgery, with Charles Elsberg at the helm. Neurosurgery then became a separate department in 1932 under the leadership of Ira Cohen. Dr. Cohen oversaw the creation of the neurosurgery residency training program 75 years ago. Since its inception, the residency program has graduated 120 residents. For more than 100 years, The Mount Sinai Hospital has been a site of clinical excellence, groundbreaking research, and technological innovation in neurosurgery. Currently, the Department of Neurosurgery has 39 clinical faculty members, performs more than 5300 surgeries and endovascular procedures annually, and is in the top 25 neurosurgical departments for NIH funding.

The Richmond Acute Subdural Hematoma Score: A Validated Grading Scale to Predict Postoperative Mortality.

BACKGROUND: Traumatic acute subdural hematomas (aSDHs) are common, life-threatening injuries often requiring emergency surgery. OBJECTIVE: To develop and validate the Richmond acute subdural hematoma (RASH) score to stratify patients by risk of mortality after aSDH evacuation. METHODS: The 2016 National Trauma Data Bank (NTDB) was queried to identify adult patients with traumatic aSDHs who underwent craniectomy or craniotomy within 4 h of arrival to an emergency department. Multivariate logistic regression modeling identified risk factors independently associated with mortality. The RASH score was developed based on a factor's strength and level of association with mortality. The model was validated using the 2017 NTDB and the area under the receiver operating characteristic curve (AUC). RESULTS: A total of 2516 cases met study criteria. The patients were 69.3% male with a mean age of 55.7 yr and overall mortality rate of 36.4%. Factors associated with mortality included age between 61 and 79 yr (odds ratio [OR] = 2.3, P < .001), age ≥80 yr (OR = 6.3, P < .001), loss of consciousness (OR = 2.3, P < .001), Glasgow Coma Scale score of ≤8 (OR = 2.6, P < .001), unilateral (OR = 2.8, P < .001) or bilateral (OR = 3.9, P < .001) unresponsive pupils, and midline shift >5 mm (OR = 1.7, P < .001). Using these risk factors, the RASH score predicted progressively increasing mortality ranging from 0% to 94% for scores of 0 to 8, respectively (AUC = 0.72). Application of the RASH score to 3091 cases from 2017 resulted in similar accuracy (AUC = 0.74). CONCLUSION: The RASH score is a simple and validated grading scale that uses easily accessible preoperative factors to predict estimated mortality rates in patients with traumatic aSDHs who undergo surgical evacuation.

The Effect of Radiation on Meningioma Volume Change.

BACKGROUND: Radiation therapy is a common treatment for meningiomas. Volume changes of meningiomas in response to radiation are not well characterized. This study seeks to quantify the volume change of meningiomas following radiation. METHODS: Data were collected from a retrospective single-institution database of cases from 2005-2015. Tumors were measured using T1-weighted post-contrast magnetic resonance imaging. Volumes were calculated using the ABC/2 ellipsoidal approximation. RESULTS: A total of 63 patients fit the inclusion criteria; 37 patients (59%) received radiation following resection, 19 (30%) received radiation alone, 4 (6%) received radiation following a biopsy, and 3 (5%) had unknown surgical status. A total of 39 patients (62%) had skull base meningiomas; 43 tumors were World Health Organization (WHO) grade I, and 12 tumors were WHO grade II. Thirteen patients received radiosurgery, 43 received radiotherapy, and 7 received an unknown number of treatments. Eight patients did not attain local control and were excluded from volume analyses. WHO grade I meningiomas saw an average of 33% ± 19% decrease in tumor volume; WHO grade II tumor volumes decreased by an average 30% ± 23%. Radiosurgery saw an average volume decrease of 34% ± 13%, while radiotherapy resulted in volume decrease of 31% ± 21%. For those who achieved local control, there was an average decrease in tumor size of 30% ± 19%, 30% ± 22%, and 41% ± 19% over 0.5-1.5, 2.5-3.5, and >5 years, respectively. CONCLUSIONS: Meningiomas treated with radiation exhibit nonlinear decrease in size over time. The greatest decrease in tumor volume occurs within the first year and begins to plateau 5 years post-radiation treatment.

Comorbid Medical Conditions as Predictors of Overall Survival in Glioblastoma Patients.

Glioblastoma (GBM) is an aggressive central nervous system tumor with a poor prognosis. This study was conducted to determine any comorbid medical conditions that are associated with survival in GBM. Data were collected from medical records of all patients who presented to VCU Medical Center with GBM between January 2005 and February 2015. Patients who underwent surgery/biopsy were considered for inclusion. Cox proportional hazards regression modeling was performed to assess the relationship between survival and sex, race, and comorbid medical conditions. 163 patients met inclusion criteria. Comorbidities associated with survival on individual-characteristic analysis included: history of asthma (Hazard Ratio [HR]: 2.63; 95% Confidence Interval [CI]: 1.24-5.58; p = 0.01), hypercholesterolemia (HR: 1.95; 95% CI: 1.09-3.50; p = 0.02), and incontinence (HR: 2.29; 95% CI: 0.95-5.57; p = 0.07). History of asthma (HR: 2.22; 95% CI: 1.02-4.83; p = 0.04) and hypercholesterolemia (HR: 1.99; 95% CI: 1.11-3.56; p = 0.02) were associated with shorter survival on multivariable analysis. Surgical patients with GBM who had a prior history of asthma or hypercholesterolemia had significantly higher relative risk for mortality on individual-characteristic and multivariable analyses.

Comparison of ABC/2 estimation and a volumetric computerized method for measurement of meningiomas using magnetic resonance imaging.

INTRODUCTION: Measurement of tumor growth rates over time for patients with meningiomas has important prognostic and therapeutic implications. Our objective was to compare two methods of measuring meningioma volume: (1) the simplified ellipsoid (ABC/2) method; and (2) perimetric volume measurements using imaging software modules. METHODS: Patients with conservatively managed meningiomas for at least 1.5 years were retrospectively identified from the VCU Brain and Spine Tumor Registry over a 10-year period (2005-2015). Tumor volumes were independently measured using the simplified ellipsoid and computerized perimetric methods. Intra class correlations (CC) and Bland-Altman analyses were performed. RESULTS: A total of 26 patients representing 29 tumors were identified. Across 146 images, there were 24 (16%) images that were non-measurable using standard application commands with the computerized perimetric method. The mean volume obtained using the ABC/2 and computerized perimetric methods were 3.2 ± 3.4 cm3 and 3.4 ± 3.5 cm3, respectively. The mean volume difference was 0.2 cm3 (SE = 0.12; p = 0.10) across measurement methods. The concordance correlation coefficient (CCC) between methods was 0.95 (95% CI 0.91, 0.98). CONCLUSIONS: There is excellent correlation between the simplified ellipsoid and computerized perimetric methods of volumetric analysis for conservatively managed meningiomas. The simplified ellipsoid method remains an excellent method for meningioma volume assessment and had an advantage over the perimetric method which failed to allow measurement of roughly one in six tumors on imaging.

Outcomes after craniotomy for resection of craniopharyngiomas in adults: analysis of the National Surgical Quality Improvement Program (NSQIP).

PURPOSE: Craniopharyngiomas occur in suprasellar locations that pose challenges for surgical management. This study evaluates the incidence of complications following craniotomy for craniopharyngioma in adults and investigates risk factors for these complications. METHODS: Patients who underwent craniotomy for excision of craniopharyngioma were identified from the 2005-2016 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Incidence of 30-day postoperative complications was determined. Multivariable logistic regression identified demographic, comorbid and perioperative characteristics associated with any complication and major (Clavien IV) complications.  RESULTS: There were 143 cases identified. Fifty-one (35.7%) had a complication, twenty (14.0%) experienced a major complication and there were four (2.8%) deaths. The most common complications were: unplanned readmission (13.3%), prolonged ventilation > 48 h (9.8%), and unplanned reoperation (9.3%). In multivariable analysis, variables significantly associated with any complication were: black race (OR 0.16; 95% CI 0.03-0.84; p = 0.03), hypertension (OR 5.04; 95% CI 1.79-14.17; p = 0.002) and longer duration of surgery (OR 1.27; 95% CI 1.01-1.58; p = 0.04). Hypertension (OR 9.33; 95% CI 1.61-54.21; p = 0.01) and longer duration of surgery (OR 1.51; 95% CI 1.05-2.17; p = 0.03) were also significant predictors for major complications. CONCLUSION: One-third of patients undergoing craniotomy for craniopharyngioma resection experienced a postoperative complication. While high, this contrasts previously reported rates of two-thirds. Prolonged operative time and hypertension are positive predictors of major complications. This information can assist in counseling patients and decision-making for management. We note that other treatment approaches, such as endoscopic surgical techniques, radiosurgery and radiation therapy likely have different profiles and predictors of complications.

Mapping an epitope in EBNA-1 that is recognized by monoclonal antibodies to EBNA-1 that cross-react with dsDNA.

INTRODUCTION: The Epstein Barr Virus (EBV) has been associated with the autoimmune disease, Systemic Lupus Erythematosus (SLE). EBV nuclear antigen-I (EBNA-1) is the major nuclear protein of EBV. We previously generated an IgG monoclonal antibody (MAb) to EBNA-1, 3D4, and demonstrated that it cross-reacts with double stranded DNA (dsDNA) and binds the 148 amino acid viral binding site (VBS) in the carboxyl region of EBNA-1. The aim of the present study was to characterize another antibody to EBNA-1 that cross-reacts with dsDNA, compare its immunoglobulin genes to 3D4, and finely map the epitope in EBNA-1 that is recognized by these cross-reactive antibodies. METHODS: We generated an IgM MAb to EBNA-1, 16D2, from EBNA-1 injected mice and demonstrated by ELISA that it cross-reacts with dsDNA and binds the 148 amino acid VBS. We sequenced the variable heavy and light chain genes of 3D4 and 16D2 and compared V gene usage. To more finely map the epitope in EBNA-1 recognized by these MAbs, we examined their binding by ELISA to 15 overlapping peptides spanning the 148 amino acid domain. RESULTS: Sequence analysis revealed that 3D4 and 16D2 utilize different VH and VL genes but identical JH and Jk regions with minimal junctional diversity. This accounts for similarities in their CDR3 regions and may explain their similar dual binding specificity. Epitope mapping revealed 3D4 and 16D2 bind the same peptide in the VBS. Based on the crystal structure of EBNA-1, we observed that this peptide resides at the base of an exposed proline rich loop in EBNA-1. CONCLUSION: We have demonstrated that two MAbs that bind EBNA-1 and cross-react with dsDNA, recognize the same peptide in the VBS. This peptide may serve as a mimetope for dsDNA and may be of diagnostic and therapeutic value in SLE.