BACKGROUND AND OBJECTIVES:In recent years, there has been an outpouring of scoring systems that were built to predict outcomes after various surgical procedures; however, research validating these studies in spinal surgery is quite limited. In this study, we evaluated the predictability of the American College of Surgeons National Surgical Quality Improvement Program Surgical Risk Calculator (ACS NSQIP SRC) for various postoperative outcomes after spinal deformity surgery. METHODS:A retrospective chart review was conducted to identify patients who underwent spinal deformity surgery at our hospital between January 1, 2014, and December 31, 2022. Demographic and clinical data necessary to use the ACS NSQIP SRC and postoperative outcomes were collected for these patients. Predictability was analyzed using the area under the curve (AUC) of receiver operating characteristic curves and Brier scores. RESULTS:Among the 159 study patients, the mean age was 64.5 ± 9.5 years, mean body mass index was 31.9 ± 6.6, and 95 (59.7%) patients were women. The outcome most accurately predicted by the ACS NSQIP SRC was postoperative pneumonia (observed = 5.0% vs predicted = 3.2%, AUC = 0.75, Brier score = 0.05), but its predictability still fell below the acceptable threshold. Other outcomes that were underpredicted by the ACS NSQIP SRC were readmission within 30 days (observed = 13.8% vs predicted = 9.0%, AUC = 0.63, Brier score = 0.12), rate of discharge to nursing home or rehabilitation facilities (observed = 56.0% vs predicted = 46.6%, AUC = 0.59, Brier = 0.26), reoperation (observed 11.9% vs predicted 5.4%, AUC = 0.60, Brier = 0.11), surgical site infection (observed 9.4% vs predicted 3.5%, AUC = 0.61, Brier = 0.05), and any complication (observed 33.3% vs 19%, AUC = 0.65, Brier = 0.23). Predicted and observed length of stay were not significantly associated (β = 0.132, P = .47). CONCLUSION:The ACS NSQIP SRC is a poor predictor of outcomes after spinal deformity surgery.

BACKGROUND AND OBJECTIVES:C5 nerve palsy is a debilitating complication of cervical spine surgery that can occur after certain approaches. To our knowledge, no previous systematic reviews have compared the rates of C5 nerve palsy after different cervical approaches, identifying the rate at which this complication becomes permanent. We aimed to compare the rates of C5 palsy after different cervical spine surgery approaches and the rates of recovery when C5 palsy was present. METHODS:A literature search of the PubMed and Embase databases from their inception to July 1, 2023, was completed to identify studies that focused on cervical spine surgery. Studies were excluded if they did not provide the rate of C5 palsy occurrence or define which surgical approaches were used. A pooled, weighted prevalence rate of C5 palsy was calculated for each approach, including the rate of permanent C5 palsy. RESULTS:A total of 155 studies met the inclusion criteria. Of these studies, 22 (14.2%) reported on laminectomies, 77 (49.7%) on laminoplasties, 38 (24.5%) on posterior cervical decompression and fusion, 39 (25.2%) on anterior cervical diskectomy and fusion, and 4 (2.6%) on corpectomies. Patients who had laminectomies had the highest incidence of C5 palsy at a pooled rate of 8%, of which 1.44% of cases were permanent. This was followed by posterior cervical decompression and fusion with a rate of 7.03% and a permanence rate of 1.02%. Patients receiving laminoplasties had a C5 palsy incidence of 5.11%; of these, 0.28% of cases were permanent. Patients who had corpectomies had an incidence of 4.16%; those who had anterior cervical diskectomy and fusions had the lowest incidence of 2.61%, of which 1.06% of cases were permanent. CONCLUSION:C5 nerve palsy is a known complication after cervical spine surgeries, with increased rates in posterior approaches, although the rate of these complications becoming permanent is minimal.

INTRODUCTION: C5 nerve palsy is a debilitating operative complication of cervical surgery and occurs commonly as many surgical approaches operate near the exiting nerve root. No prior study has attempted to identify the recovery rate of C5 nerve palsy after cervical operations, and identify the rate of which this complication becomes permanent. METHODS: A literature search of the PubMed and Embase databases was completed to identify all papers focused on cervical surgery. Studies were excluded if they did not provide the rate of C5 palsy occurrence or if they did not define what type of cervical surgery was completed. A pooled, weighted prevalence rate of C5 palsy was calculated for each type of surgery, including the rate of these becoming permanent. RESULTS: A total of 118 studies were identified and met all inclusion criteria. Of these studies, 52 were focused on laminoplasties, 24 on anterior cervical discectomy fusions (ACDF), 22 on laminectomies without fusion, and 20 on posterior cervical fusions (PCF). Laminectomies had the highest incidence of C5 palsy at a pooled rate of 7.08% (95% Confidence Interval [CI], 4.74%-10.46%, I2 = 87%, P < .01), of which 0.05% (CI = 0.00%-0.90%) were permanent. This was followed by PCFs with a rate of 6.70% (CI = 4.50%-9.85%), with the effects being permanent at a rate of 0.04% (CI = 0.00%-1.20%). Laminoplasties had a C5 palsy incidence of 5.49% (CI = 4.65%-6.47%), of these 0.02% (CI = 0.00%-0.11%) were permanent. ACDFs had the lowest incidence at a rate of 4.50% (CI = 2.56%-7.79%), of which only 0.02% (CI = 0.04%-0.08%) were permanent. CONCLUSIONS: C5 nerve palsy is a relatively common complication after all types of cervical surgeries with increased rates in posterior approaches, however the rate of these becoming permanent is minimal.

Background Survival is variable in patients with glioblastoma IDH wild-type (GBM), even after comparable surgical resection of radiographically detectable disease, highlighting the limitations of radiographic assessment of infiltrative tumor anatomy. The majority of postsurgical progressive events are failures within 2 cm of the resection margin, motivating supramaximal resection strategies to improve local control. However, which patients benefit from such radical resections remains unknown. Methods We developed a predictive model to identify which IDH wild-type GBMs are amenable to radiographic gross-total resection (GTR). We then investigated whether GBM survival heterogeneity following GTR is correlated with microscopic tumor burden by analyzing tumor cell content at the surgical margin with a rapid qPCR-based method for detection of TERT promoter mutation. Results Our predictive model for achievable GTR, developed on retrospective radiographic and molecular data of GBM patients undergoing resection, had an area under the curve of 0.83, sensitivity of 62%, and specificity of 90%. Prospective analysis of this model in 44 patients found that 89% of patients were correctly predicted to achieve a residual volume (RV) < 4.9cc. Of the 44 prospective patients undergoing rapid qPCR TERT promoter mutation analysis at the surgical margin, 7 had undetectable TERT mutation, of which 5 also had a GTR (RV < 1cc). In these 5 patients at 30 months follow-up, 75% showed no progression, compared to 0% in the group with TERT mutations detected at the surgical margin (P = .02). Conclusions These findings identify a subset of patients with GBM that may derive local control benefits from radical resection to undetectable molecular margins.

Delays and risks associated with neurosurgical biopsies preclude timely diagnosis and treatment of central nervous system (CNS) lymphoma and other CNS neoplasms. We prospectively integrated targeted rapid genotyping of cerebrospinal fluid (CSF) into the evaluation of 70 patients with CNS lesions of unknown etiology. Participants underwent genotyping of CSF-derived DNA using a qPCR-based approach for parallel detection of single-nucleotide variants in the MYD88, TERT promoter, IDH1, IDH2, BRAF and H3F3A genes within 80 minutes of sample acquisition. Canonical mutations were detected in 42% of patients with neoplasms, including cases of primary and secondary CNS lymphoma, glioblastoma, IDH-mutant brainstem glioma and H3K27M-mutant diffuse midline glioma. Genotyping results eliminated the need for surgical biopsies in 7/33 (21.2%) cases of newly diagnosed neoplasms, resulting in significantly accelerated initiation of disease-directed treatment (median 3 vs 12 days; p = 0.027). This assay was then implemented in a Clinical Laboratory Improvement Amendments (CLIA) environment, with 2-day median turnaround for diagnosis of central nervous system lymphoma from 66 patients across 4 clinical sites. Our study prospectively demonstrates that targeted rapid CSF genotyping influences oncologic management for suspected CNS tumors.-

INTRODUCTION: The intersection of mental health and patient reported outcomes after various neurosurgical procedures has been well published. Although there is paucity in the literature focused on the surgical outcomes of patients after spinal fusion and their relationship with the patient’s mental state before surgery. METHODS: The National Inpatient Sample (NIS) database was utilized, with a search identifying all patients who underwent a spinal fusion in all years between 2009-2020. Once patients were identified, diagnosis codes for major psychiatric disorders (depression, anxiety, bipolar disorder) were utilized to separate sample into a psychiatric disorder cohort, and a control sample. Univariate and multivariate linear/logistic regression models were utilized to analyze data. RESULTS: A total of 2,877,241 patients were identified from this database, of which 647,951 (22.5%) of patients had a preoperative diagnosis of at least one of the psychiatric disorders. Univariate analysis of patient demographics in the psychiatric disorder cohort demonstrated that these patients were more likely to be female (67.26% vs. 50.74%, P < .001), and younger (58.88 years vs. 59.11 years, P < .001) when compared to control cohort. Increased rates of respiratory (P < .001), urinary (P < .001), cardiac (P < .001) complications were seen in the psychiatric disorder cohort. On multivariate analysis patients had increased odds of fusion disorders (OR, 1.62; 95% CI, 1.55-1.70, P < .001), mechanical injuries (OR, 1.27; 95% CI, 1.20-1.35, P < .001), and postoperative hematomas (OR, 1.29; 95% CI, 1.26-1.33; P < .001). CONCLUSIONS: Preoperative diagnosis of various psychiatric conditions have notable effects on postoperative outcomes after spinal fusion and should be evaluated preoperatively.

INTRODUCTION: The low yields of CSF studies and serologies in current diagnostic workflows for suspected CNS neoplasms often lead to neurosurgical biopsies of high-risk lesions. To address this need, we developed an assay to rapidly identify hallmark mutations of CNS neoplasms in CSF. METHODS: Targeted Rapid Sequencing (TetRS) was developed as a qPCR-based method to detect IDH1/2, TERT promoter, BRAF, H3F3A, and MYD88 mutations in CSF-derived DNA within 80 minutes of collection. CSF was prospectively collected over 18 months from 98 patients with suspected new CNS neoplasms. Results were utilized in clinical decision-making. RESULTS: 40 of 98 patients were ultimately diagnosed with a neoplasm. TetRS detected a mutation in 15 out of 40 patients with a neoplasm (37.5%), including cases of CNS lymphoma, glioblastoma, IDH-mutant brainstem glioma and H3K27M-mutant diffuse midline glioma. Detection of a mutation accelerated diagnosis in comparison to cases where a mutation was not detected (median 0.5 vs 10.5 days, p < 0.00001). In multiple cases, a positive TetRS result obviated the need for biopsy and enabled initiation of disease-directed therapy. In one such case, detection of the MYD88 L265P variant was diagnostic of CNS lymphoma, enabling methotrexate and rituximab initiation within 3 days of admission. Results of repeated CSF samplings correlated with treatment response and recurrence. In another case, detection of the IDH1 R132G variant was diagnostic of IDH-mutant brainstem glioma, enabling IDH inhibitor and radiation therapy, with clinical and radiographic response. CONCLUSIONS: The targeted cell-free DNA panel for CSF presented here is a novel tool to rapidly, cost-effectively and broadly diagnose CNS neoplasia, initiate therapies and follow disease progression in the absence of neurosurgical tissue sampling.

Abstract This protocol describes a qPCR-based assay that is designed to detect twelve potential mutations from clinical specimens that are significant to CNS neoplasms. The assay is optimized for plasma and cerebrospinal fluid (CSF), where both cell-free DNA (cfDNA) and DNA derived from circulating tumor cells (CTCs) can be analyzed.

Diagnosing primary central nervous system lymphoma (PCNSL) frequently requires neurosurgical biopsy due to nonspecific radiologic features and the low yield of cerebrospinal fluid (CSF) studies. We characterized the clinical evaluation of suspected PCNSL (N = 1007 patients) and designed a rapid multiplexed genotyping assay for MYD88, TERT promoter, IDH1/2, H3F3A, and BRAF mutations to facilitate the diagnosis of PCNSL from CSF and detect other neoplasms in the differential diagnosis. Among 159 patients with confirmed PCNSL, the median time to secure a diagnosis of PCNSL was 10 days, with a range of 0 to 617 days. Permanent histopathology confirmed PCNSL in 142 of 152 biopsies (93.4%), whereas CSF analyses were diagnostic in only 15/113 samplings (13.3%). Among 86 archived clinical specimens, our targeted genotyping assay accurately detected hematologic malignancies with 57.6% sensitivity and 100% specificity (95% confidence interval [CI]: 44.1% to 70.4% and 87.2% to 100%, respectively). MYD88 and TERT promoter mutations were prospectively identified in DNA extracts of CSF obtained from patients with PCNSL and glioblastoma, respectively, within 80 minutes. Across 132 specimens, hallmark mutations indicating the presence of malignancy were detected with 65.8% sensitivity and 100% specificity (95% CI: 56.2%-74.5% and 83.9%-100%, respectively). This targeted genotyping approach offers a rapid, scalable adjunct to reduce diagnostic and treatment delays in PCNSL.

Primary central nervous system lymphoma (PCNSL) remains challenging to diagnose due to nonspecific clinical and radiologic features and low diagnostic yields of cerebrospinal fluid (CSF) studies. We sought to characterize the diagnostic approach of suspected PCNSL, in order to improve clinical workflow. We first reviewed 1,007 new brain lesions of unknown etiology that included PCNSL in the radiologic differential diagnosis. The most common final diagnoses included high-grade glioma (28.2%) and PCNSL (14.6%). Diagnostic biopsies were frequently performed for high-grade glioma (100%) and PCNSL (94.4%), while CSF was frequently sampled for PCNSL (78.7%). We next identified 159 patients with an established new diagnosis of PCNSL. CSF studies were non-diagnostic in 86.7% of cases, whereas biopsy was positive in 93%. However, intraoperative histopathology was inconclusive for PNCSL in 54.5%, likely contributing to 22% of patients undergoing surgical resection. These challenges resulted in 12 days median time to treatment initiation, and readmission for further workup or treatment initiation in 27% of patients. These results indicated the need for a rapid, sensitive and specific platform to segregate PCNSL and glioma using CSF and tissue samples. We developed a qPCR-based assay to genotype the MYD88 L265P hotspot mutation from CSF and plasma within 80 minutes of sample acquisition. Results were concordant with orthogonal DNA sequencing in extracts from 87 archived specimens, with detection limits of 490pg of input genomic DNA and 0.15% mutant allele frequency. When performed simultaneously with assays for TERT promoter, IDH1/2, H3F3A and BRAF point mutations, the resulting panel accurately segregated PCNSL and adult diffuse glioma molecular diagnoses in 87 archived specimens and 19 prospective liquid biopsies, including cases of lymphoma and glioma. We propose that inclusion of targeted analysis of these mutually exclusive recurrent molecular alterations characterizing gliomas and PCNSL will facilitate rapid, sensitive diagnosis from solid and liquid biopsies.