Rapid detection of IDH mutations in gliomas by intraoperative mass spectrometry.

The development and performance of two mass spectrometry (MS) workflows for the intraoperative diagnosis of isocitrate dehydrogenase (IDH) mutations in glioma is implemented by independent teams at Mayo Clinic, Jacksonville, and Huashan Hospital, Shanghai. The infiltrative nature of gliomas makes rapid diagnosis necessary to guide the extent of surgical resection of central nervous system (CNS) tumors. The combination of tissue biopsy and MS analysis used here satisfies this requirement. The key feature of both described methods is the use of tandem MS to measure the oncometabolite 2-hydroxyglutarate (2HG) relative to endogenous glutamate (Glu) to characterize the presence of mutant tumor. The experiments i) provide IDH mutation status for individual patients and ii) demonstrate a strong correlation of 2HG signals with tumor infiltration. The measured ratio of 2HG to Glu correlates with IDH-mutant (IDH-mut) glioma (P < 0.0001) in the tumor core data of both teams. Despite using different ionization methods and different mass spectrometers, comparable performance in determining IDH mutations from core tumor biopsies was achieved with sensitivities, specificities, and accuracies all at 100%. None of the 31 patients at Mayo Clinic or the 74 patients at Huashan Hospital were misclassified when analyzing tumor core biopsies. Robustness of the methodology was evaluated by postoperative re-examination of samples. Both teams noted the presence of high concentrations of 2HG at surgical margins, supporting future use of intraoperative MS to monitor for clean surgical margins. The power of MS diagnostics is shown in resolving contradictory clinical features, e.g., in distinguishing gliosis from IDH-mut glioma.

Repeated surgical resections for management of high-grade glioma and its impact on quality of life.

PURPOSE: High-grade gliomas (HGG) are aggressive cancers, and their recurrence is inevitable, despite advances in treatment options. While repeated tumor resection has been shown to increase survival rate, its impact on quality of life is not clearly defined. To address this gap, we compared quality of life (QoL) changes in HGG patients who underwent first-time (FTR) versus repeat surgical resections (RSR) for management of recurrence. METHODS: Forty-four adults with HGG who underwent tumor resection were included in this study and classified into either the FTR group (n = 23) or the RSR group (n = 21). All patients completed comprehensive neuropsychological evaluations that included the Functional Assessment of Cancer Therapy-General (FACT-G) and Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) scales, pre-operatively and at two weeks post-operatively. RESULTS: There was no difference between the FTR and RSR groups in any of the QoL indices (all p > .05), except for improved emotional well-being and worsened social well-being, suggesting minimal detrimental effects of repeat surgeries on QoL in comparison to first time surgery. CONCLUSIONS: These results suggest that repeated resection is a viable strategy in certain cases for management of HGG recurrence, with similar impact on QoL as observed in patients undergoing first time surgery. These encouraging outcomes provide useful insight to guide treatment strategies and patient and clinician decision making to optimize surgical and functional outcomes.

SARS-CoV2 entry factors are expressed in primary human glioblastoma and recapitulated in cerebral organoid models.

PURPOSE: Glioblastoma (GBM) is the most common and malignant primary brain tumor in adults with a median overall survival of only 14.6 months despite aggressive treatment. While immunotherapy has been successful in other cancers, its benefit has been proven elusive in GBM, mainly due to a markedly immunosuppressive tumor microenvironment. SARS-CoV-2 has been associated with the development of a pronounced central nervous system (CNS) inflammatory response when infecting different cells including astrocytes, endothelial cells, and microglia. While SARS-CoV2 entry factors have been described in different tissues, their presence and implication on GBM aggressiveness or microenvironment has not been studied on appropriate preclinical models. METHODS: We evaluated the presence of crucial SARS-CoV-2 entry factors: ACE2, TMPRSS2, and NRP1 in matched surgically-derived GBM tissue, cells lines, and organoids; as well as in human brain derived specimens using immunohistochemistry, confocal pixel line intensity quantification, and transcriptome analysis. RESULTS: We show that patient derived-GBM tissue and cell cultures express SARS-CoV2 entry factors, being NRP1 the most crucial facilitator of SARS-CoV-2 infection in GBM. Moreover, we demonstrate that, receptor expression remains present in our GBM organoids, making them an adequate model to study the effect of this virus in GBM for the potential development of viral therapies in the future. CONCLUSION: Our findings suggest that the SARS-CoV-2 virus entry factors are expressed in primary tissues and organoid models and could be potentially utilized to study the susceptibility of GBM to this virus to target or modulate the tumor microenviroment.

Enhanced sensitivity of electrocorticography during awake craniotomy using a novel circular grid electrode.

PURPOSE: Awake craniotomy with intraoperative functional brain mapping (FBM) bedside neurological testing is an important technique used to optimize resective brain surgeries near eloquent cortex. Awake craniotomy performed with electrocorticography (ECoG) and direct electrical stimulation (DES) for FBM can delineate eloquent cortex from lesions and epileptogenic regions. However, current electrode technology demonstrates spatial limitations. Our group has developed a novel circular grid with the goal of improving spatial recording of ECoG to enhance detection of ictal and interictal activity. METHODS: This retrospective study was approved by the institutional review board at Mayo Clinic Florida. We analyzed patients undergoing awake craniotomy with ECoG and DES and compared ECoG data obtained using the 22 contact circular grid to standard 6 contact strip electrode. RESULTS: We included 144 cases of awake craniotomy with ECoG, 73 using circular grid and 71 with strip electrode. No significant differences were seen regarding preoperative clinical and demographic data, duration of ECoG recording (p = 0.676) and use of DES (p = 0.926). Circular grid was more sensitive in detecting periodic focal epileptiform discharges (PFEDs) (p = 0.004), PFEDs plus (p = 0.032), afterdischarges (ADs) per case (p = 0.022) at lower minimum (p = 0.012) and maximum (p < 0.0012) intensity stimulation, and seizures (p = 0.048). PFEDs (p < 0.001), PFEDs plus (p < 0.001), and HFOs (p < 0.001) but not ADs (p = 0.255) predicted electrographic seizures. CONCLUSION: We demonstrate higher sensitivity in detecting ictal and interictal activity on ECoG during awake craniotomy with a novel circular grid compared to strip electrode, likely due to better spatial sampling during ECoG. We also found association between PFEDs and intraoperative seizures.

Systemic Therapy for Melanoma Brain and Leptomeningeal Metastases.

OPINION STATEMENT: Melanoma has a high propensity to metastasize to the brain which portends a poorer prognosis. With advanced radiation techniques and targeted therapies, outcomes however are improving. Melanoma brain metastases are best managed in a multi-disciplinary approach, including medical oncologists, neuro-oncologists, radiation oncologists, and neurosurgeons. The sequence of therapies is dependent on the number and size of brain metastases, status of systemic disease control, prior therapies, performance status, and neurological symptoms. The goal of treatment is to minimize neurologic morbidity and prolong both progression free and overall survival while maximizing quality of life. Surgery should be considered for solitary metastases, or large and/or symptomatic metastases with edema. Stereotactic radiosurgery offers a benefit over whole-brain radiation attributed to the relative radioresistance of melanoma and reduction in neurotoxicity. Thus far, data supports a more durable response with systemic therapy using combination immunotherapy of ipilimumab and nivolumab, though targeting the presence of BRAF mutations can also be utilized. BRAF inhibitor therapy is often used after immunotherapy failure, unless a more rapid initial response is needed and then can be done prior to initiating immunotherapy. Further trials are needed, particularly for leptomeningeal metastases which currently require the multi-disciplinary approach to determine best treatment plan.

Cervical chordomas: multicenter case series and meta-analysis.

BACKGROUND: En bloc spondylectomy is the gold standard for surgical resection of sacral chordomas (CHO), but the effect of extent of resection on recurrence and survival in patients with CHO of the cervical spine remains elusive. METHODS: MEDLINE, Embase, Scopus, and Cochrane were systematically reviewed. Patients with cervical CHO treated at three tertiary-care academic institutions were reviewed for inclusion. We performed an individual participant data meta-analysis to assess the overall survival (OS) and progression free survival (PFS) after en bloc-gross total resection (GTR) and intralesional-GTR compared to subtotal resection (STR). We then performed an intention-to-treat analysis including all patients with attempted en bloc resection in the en bloc group, regardless of the surgical margins. RESULTS: There was a total of 13 series including 161 patients with cervical CHO, including our current series of 22 patients. GTR (en bloc-GTR + intralesional-GTR) was associated with a significant decrease in the risk of local progression (pooled hazard ratio (PHR) = 0.22; 95% CI 0.08-0.59; p = 0.003) and risk of death (PHR 0.31; 95%; CI 0.12-0.83; p = 0.020). A meta-regression analyses determined that intralesional-GTR improved PFS (PHR 0.35; 95% CI 0.16-0.76; p = 0.009) as well as OS (PHR 0.25; 95% CI 0.08-0.79; p = 0.019) when compared to STR. En bloc-GTR was associated with a significant reduction in the risk of local progression (PHR 0.06; 95% CI 0.01-0.77; p = 0.030), but not a decreased OS (PHR 0.50; 95% CI 0.19-1.27; p = 0.145). Our intention-to-treat analyses revealed a near significant improvement in OS for the en bloc group (PHR: 0.15; 95% CI 0.02-1.22; p = 0.054), and nearly identical improvement in PFS. Radiation data was not available for the studies included in the meta-analysis. CONCLUSION: This is the first and only meta-analysis of patients with cervical CHO. We found that both en bloc-GTR and intralesional-GTR resulted in improved local tumor control when compared to STR.

The Adaptive Immune Landscape of the Colorectal Adenoma-Carcinoma Sequence.

BACKGROUND: The tumor immune microenvironment exerts a pivotal influence in tumor initiation and progression. The aim of this study was to analyze the immune context of sporadic and familial adenomatous polyposis (FAP) lesions along the colorectal adenoma-carcinoma sequence (ACS). METHODS: We analyzed immune cell counts (CD3+, CD4+, CD8+, Foxp3+, and CD57+), tumor mutation burden (TMB), MHC-I expression and PD-L1 expression of 59 FAP and 74 sporadic colorectal lesions, encompassing adenomas with low-grade dysplasia (LGD) (30 FAP; 30 sporadic), adenomas with high-grade dysplasia (22 FAP; 30 sporadic), and invasive adenocarcinomas (7 FAP; 14 sporadic). RESULTS: The sporadic colorectal ACS was characterized by (1) a stepwise decrease in immune cell counts, (2) an increase in TMB and MHC-I expression, and (3) a lower PD-L1 expression. In FAP lesions, we observed the same patterns, except for an increase in TMB along the ACS. FAP LGD lesions harbored lower Foxp3+ T cell counts than sporadic LGD lesions. A decrease in PD-L1 expression occurred earlier in FAP lesions compared to sporadic ones. CONCLUSIONS: The colorectal ACS is characterized by a progressive loss of adaptive immune infiltrate and by the establishment of a progressively immune cold microenvironment. These changes do not appear to be related with the loss of immunogenicity of tumor cells, or to the onset of an immunosuppressive tumor microenvironment.

Genomic prediction of breeding values for carcass traits in Nellore cattle.

BACKGROUND: The objective of this study was to evaluate the accuracy of genomic predictions for rib eye area (REA), backfat thickness (BFT), and hot carcass weight (HCW) in Nellore beef cattle from Brazilian commercial herds using different prediction models. METHODS: Phenotypic data from 1756 Nellore steers from ten commercial herds in Brazil were used. Animals were offspring of 294 sires and 1546 dams, reared on pasture, feedlot finished, and slaughtered at approximately 2 years of age. All animals were genotyped using a 777k Illumina Bovine HD SNP chip. Accuracy of genomic predictions of breeding values was evaluated by using a 5-fold cross-validation scheme and considering three models: Bayesian ridge regression (BRR), Bayes C (BC) and Bayesian Lasso (BL), and two types of response variables: traditional estimated breeding value (EBV), and phenotype adjusted for fixed effects (Y*). RESULTS: The prediction accuracies achieved with the BRR model were equal to 0.25 (BFT), 0.33 (HCW) and 0.36 (REA) when EBV was used as response variable, and 0.21 (BFT), 0.37 (HCW) and 0.46 (REA) when using Y*. Results obtained with the BC and BL models were similar. Accuracies increased for traits with a higher heritability, and using Y* instead of EBV as response variable resulted in higher accuracy when heritability was higher. CONCLUSIONS: Our results indicate that the accuracy of genomic prediction of carcass traits in Nellore cattle is moderate to high. Prediction of genomic breeding values from adjusted phenotypes Y* was more accurate than from EBV, especially for highly heritable traits. The three models considered (BRR, BC and BL) led to similar predictive abilities and, thus, either one could be used to implement genomic prediction for carcass traits in Nellore cattle.

Na/K-ATPase as a target for anticancer drugs: studies with perillyl alcohol.

BACKGROUND: Na/K-ATPase (NKA) is inhibited by perillyl alcohol (POH), a monoterpene used in the treatment of tumors, including brain tumors. The NKA α1 subunit is known to be superexpressed in glioblastoma cells (GBM). This isoform is embedded in caveolar structures and is probably responsible for the signaling properties of NKA during apoptosis. In this work, we showed that POH acts in signaling cascades associated with NKA that control cell proliferation and/or cellular death. METHODS: NKA activity was measured by the amount of non-radioactive Rb(+) incorporation into cultured GBM cell lines (U87 and U251) and non-tumor cells (mouse astrocytes and VERO cells). Cell viability was measured by lactate dehydrogenase levels in the supernatants of POH-treated cells. Activated c-Jun N-terminal Kinase (JNK) and p38 were assessed by western blotting. Apoptosis was detected by flow cytometry and immunocytochemistry, and the release of interleukins was measured by ELISA. RESULTS: All four cell types tested showed a similar sensitivity for POH. Perillic acid (PA), the main metabolite of POH, did not show any effect on these cells. Though the cell viability decreased in a dose-dependent manner when cells were treated with POH, the maximum cytotoxic effect of PA obtained was 30% at 4 mM. 1.5 mM POH activated p38 in U87 cells and JNK in both U87 and U251 cells as well as mouse astrocytes. Dasatinib (an inhibitor of the Src kinase family) and methyl ß-cyclodextrin (which promotes cholesterol depletion in cell membranes) reduced the POH-induced activation of JNK1/2 in U87 cells, indicating that the NKA-Src complex participates in this mechanism. Inhibition of JNK1/2 by the JNK inhibitor V reduced the apoptosis of GBM cells that resulted from POH administration, indicating the involvement of JNK1/2 in programmed cell death. 1.5 mM POH increased the production of interleukin IL-8 in the U251 cell supernatant, which may indicate a possible strategy by which cells avoid the cytotoxic effects of POH. CONCLUSIONS: A signaling mechanism mediated by NKA may have an important role in the anti-tumor action of POH in GBM cells.

Single-Photon Emission Computed Tomography (SPECT-CT) as a Predictor of Pain Generators in Patients Undergoing Anterior Cervical Discectomy and Fusion (ACDF) for Axial Cervical Pain.

BACKGROUND: Axial neck pain is often associated with cervical instability, and surgical options are often reserved for patients with either neurological compromise or deformity of the spine. However, cervical facet arthropathy is often implicated with instability and the location of painful generators is often difficult to ascertain. Single-photon emission computed tomography (SPECT-CT) presents an adjunct to conventional imaging in the workup of patients with suspected facetogenic pain. We aimed to report our experience with patients undergoing anterior cervical discectomy and fusion (ACDF) guided by SPECT-CT for axial cervical pain. METHODS: We retrospectively identified all cases undergoing ACDF that presented with axial neck pain where correlating SPECT-CT high metabolism areas were identified. Patients were treated at a tertiary care institution between January 2018 and January 2021. Patients with positive radiotracer uptake pre-operatively were compared with patients undergoing ACDF without uptake on SPECT-CT. The pre- and post-operative patients who reported neck pain at one year were compared. RESULTS: Thirty-five patients were included in this retrospective cohort. The median pre- and post-intervention (at one-year follow-up) visual analog score (VAS) of patients undergoing ACDF without uptake on SPECT-CT was 7 and 3 (p<0.01), while the pre- and post-VAS for patients undergoing surgery with positive uptake on SPECT-CT was 8.5 and 0 (p<0.01). Improvement was significantly larger for patients undergoing SPECT-CT-guided ACDF (p=0.02). At one year after surgery, none of the assessed patients required additional surgical intervention. CONCLUSION: This case series represents the experience of our group to date with patients undergoing SPECT-CT-guided ACDF with results suggesting potential benefit in guiding fusion.

Wireless Stimulation of Motor Cortex Through a Collagen Dura Substitute Using an Ultra-Thin Implant Fabricated on Parylene/PDMS.

We present the design, fabrication, and in vivo testing of an ultra-thin (100 µm) wireless and battery-free implant for stimulation of the brain's cortex. The implant is fabricated on a flexible and transparent parylene/PDMS substrate, and it is miniaturized to dimensions of 15.6 × 6.6 mm 2. The frequency and pulse width of the monophasic voltage pulses are determined through On-Off keying (OOK) modulation of a wireless transmission at 2.45 GHz. Furthermore, the implant triggered a motor response in vivo when tested in 6 rodents. Limb response was observed by wireless stimulation of the brain's motor cortex through an FDA-approved collagen dura substitute that was placed on the dura in the craniotomy site, with no direct contact between the implant's electrodes and the brain's cortical surface. Therefore, the wireless stimulation method reported herein enables the concept of an e-dura substitute, where wireless electronics can be integrated onto a conventional dura substitute to augment its therapeutic function and administer any desired stimulation protocol without the need for post-surgical intervention for battery replacement or reprogramming stimulation parameters.

A Wireless Battery-Free Implant With Optical Telemetry for In Vivo Cortical Stimulation.

We present a 100 µm-thick, wireless, and battery-free implant for brain stimulation through a U.S. Food and Drug Administration-approved collagen dura substitute without contact with the brain's surface, while providing visible-light spectrum telemetry to track the onset of stimulation. The device is fabricated on a 16 × 6.67 mm2 biocompatible parylene/PDMS substrate and is encapsulated with a 2 µm-thick transparent parylene layer that enables the relay of the LED brightness. The in vivo rodent testing confirmed the implant's ability to trigger motor response while generating observable brightness through the skin. The results reveal the prospect of wireless stimulation with enhanced safety by eliminating contact between the implant and the brain, with optical telemetry for facilitated tracking.

What Factors Predict the Development of Neurologic Deficits Following Resection of Intramedullary Spinal Cord Tumors: A Multi-Center Study.

BACKGROUND: Intramedullary spinal cord tumors are challenging to resect, and their postoperative neurological outcomes are often difficult to predict, with few studies assessing this outcome. METHODS: We reviewed the medical records of all patients surgically treated for Intramedullary spinal cord tumors at our multisite tertiary care institution (Mayo Clinic Arizona, Mayo Clinic Florida, Mayo Clinic Rochester) between June 2002 and May 2020. Variables that were significant in the univariate analyses were included in a multivariate logistic regression. "MissForest" operating on the Random Forest algorithm, was used for data imputation, and K-prototype was used for data clustering. Heatmaps were added to show correlations between postoperative neurological deficit and all other included variables. Shapley Additive exPlanations were implemented to understand each feature's importance. RESULTS: Our query resulted in 315 patients, with 160 meeting the inclusion criteria. There were 53 patients with astrocytoma, 66 with ependymoma, and 41 with hemangioblastoma. The mean age (standard deviation) was 42.3 (17.5), and 48.1% of patients were women (n = 77/160). Multivariate analysis revealed that pathologic grade >3 (OR = 1.55; CI = [0.67, 3.58], P = 0.046 predicted a new neurological deficit. Random Forest algorithm (supervised machine learning) found age, use of neuromonitoring, histology of the tumor, performing a midline myelotomy, and tumor location to be the most important predictors of new postoperative neurological deficits. CONCLUSIONS: Tumor grade/histology, age, use of neuromonitoring, and myelotomy type appeared to be most predictive of postoperative neurological deficits. These results can be used to better inform patients of perioperative risk.

Prognostic value of programmed cell death ligand 1 (PD-L1) expression in patients with stage III non-small cell lung cancer under different treatment types: a retrospective study.

OBJECTIVE: Currently programmed cell death protein 1 (PD-1) inhibitors in combination with other therapies are being evaluated to determine their efficacy in cancer treatment. However, the effect of PD-ligand (L) 1 expression on disease outcomes in stage III (EC III) non-small cell lung cancer is not completely understood. Therefore, this study aimed to assess the influence of PD-L1 expression on the outcomes of EC III non-small cell lung cancer. METHODS: This study was conducted on patients diagnosed with EC III non-small cell lung cancer who underwent treatment at a tertiary care hospital. PD-L1 expression was determined using immunohistochemical staining, all patients expressed PD-L1. Survival was estimated using the Kaplan-Meier method. Relationships between variables were assessed using Cox proportional regression models. RESULTS: A total of 49 patients (median age=69 years) with EC III non-small cell lung cancer and PD-L1 expression were evaluated. More than half of the patients were men, and most were regular smokers. The patients were treated with neoadjuvant chemotherapy, surgery, or sequential or combined chemotherapy and radiotherapy. The median progression-free survival of the entire cohort was 14.2 months, and the median overall survival was 20 months. There was no significant association between PD-L1 expression and disease progression, clinical characteristics, or overall survival. CONCLUSIONS: PD-L1 expression was not correlated with EC III non-small cell lung cancer outcomes. Whether these findings differ from the association with immune checkpoint inhibitors remains to be addressed in future studies.

Frailty as a Predictor of Postoperative Morbidity and Mortality in Patients Aged 80 Years and Older Undergoing Instrumented Fusion.

BACKGROUND AND OBJECTIVES: Degenerative spine disease is a leading cause of disability, with increasing prevalence in the older patients. While age has been identified as an independent predictor of outcomes, its predictive value is limited for similar older patients. Here, we aimed to determine the most predictive frailty score of adverse events in patients aged 80 and older undergoing instrumented lumbar fusion. METHODS: We proceeded with a multisite (3 tertiary academic centers) retrospective review including patients undergoing instrumented fusion aged 80 and older from January 2010 to present. A composite end point encompassing 30-day return to operating room, readmission, and mortality was created. We estimated the area under the receiver operating characteristic curve for frailty scores (Modified Frailty Index-5 [MFI-5], Modified Frailty Index-11 [MFI-11], and Charlson Comorbidity Index [CCI]) in relation to that composite score. In addition, we estimated the association between each score and the composite end point by means of logistic regression. RESULTS: A total of 153 patients with an average age of 85 years at the time of surgery were included. We observed a 30-day readmission rate of 11.1%, reoperation of 3.9%, and mortality of 0.6%. The overall rate of the composite end point at 30 days was 25 (15.1%). The AUC for MFI-5 was 0.597 (0.501-0.693), for MFI-11 was 0.620 (0.518-0.723), and for CCI was 0.564 (0.453-0.675). The association between the scores and composite end point did not reach statistical significance for MFI-5 (odds ratio [OR] = 1.45 [0.98-2.15], P = .061) and CCI (OR = 1.13 [0.97-1.31], P = .113) but was statistically significant for MFI-11 (OR = 1.46 [1.07-2.00], P = .018). CONCLUSION: This is the largest study comparing frailty index scores in octogenarians undergoing instrumented lumbar fusion. Our findings suggest that while MFI-11 score correlated with adverse events, the predictive ability of existing scores remains limited, highlighting the need for better approaches to identify select patients at age extremes.

Intracranial aneurysms in patients with acute ischemic stroke prevalence and influence on mechanical thrombectomy over 14 years in a tertiary-care center.

INTRODUCTION: The prevalence of intracranial aneurysms (IA) in patients with acute ischemic stroke (AIS) requiring mechanical thrombectomy (MT) is unclear. OBJECTIVE: To describe the prevalence of IA in patients with AIS and their influence on MT. MATERIALS & METHODS: This is a retrospective cohort study on all patients admitted with a diagnosis of AIS from January 2008 to March 2022 at a tertiary academic center. The records were reviewed for demographic, clinical, imaging, and outcomes data. Only patients who had CTA at admission were included in this analysis. RESULTS: Among 2265 patients admitted with AIS, this diagnosis was confirmed in 2113 patients (93.3 %). We included 1111 patients (52.6 %) who had head CTA and 321 (28.9 %) who underwent MT. The observed prevalence of aneurysms on CTA was 4.5 % (50/1111 patients), and 8 (16 %) had multiple aneurysms. MT was performed in 7 patients harboring IAs: 6 ipsilateral (5 proximal and 1 distal to the occlusion)and 1 contralateral aneurysm.. The patient with a contralateral aneurysm had a TICI 2B score In patients with ipsilateral aneurysms, TICI 2B or 3 was achieved in 3 cases (50 %), which is significantly lower than historical control of MT (91.6 %) without IA (p = 0.01). No aneurysms ruptured during MT. The aneurysm noted distal to the occlusion was mycotic. CONCLUSION: In this analysis, the observed prevalence of IA in patients with AIS was 4.5%. Ipsilateral aneurysms (proximal or distal to the occlusion site) deserve particular attention, given the potential risk of rupture during MT. Aneurysms located distal to the occlusion were mycotic and the rate of recanization in patients with ipsilateral aneurysms was low compared to historical controls. Further studies are needed to improve the outcomes in patients with IA requiring MT.

Awake Craniotomy Program Implementation.

Importance: Implementing multidisciplinary teams for treatment of complex brain tumors needing awake craniotomies is associated with significant costs. To date, there is a paucity of analysis on the cost utility of introducing advanced multidisciplinary standardized teams to enable awake craniotomies. Objective: To assess the cost utility of introducing a standardized program of awake craniotomies. Design, Setting, and Participants: A retrospective economic evaluation was conducted at Mayo Clinic Florida. All patients with single, unilateral lesions who underwent elective awake craniotomies between January 2016 and December 2021 were considered eligible for inclusion. The economic perspective of the health care institution and a time horizon of 1 year were considered. Data were analyzed from October 2022 to May 2023. Exposure: Treatment with an awake craniotomy before standardization (2016-2018) compared with treatment with awake craniotomy after standardization (2018-2021). Main Outcomes and Measures: Patient demographics, perioperative, and postoperative outcomes, including length of stay, intensive care (ICU) admission, extent of resection, readmission rates, and 1-year mortality were compared between patients undergoing surgery before and after standardization. Direct medical costs were estimated from Medicare reimbursement rates for all billed procedures. A cost-utility analysis was performed considering differences in direct medical costs and in 1-year mortality within the periods before and after standardization of procedures. Uncertainty was explored in probability sensitivity analysis. Results: A total of 164 patients (mean [SD] age, 49.9 [15.7] years; 98 [60%] male patients) were included in the study. Of those, 56 underwent surgery before and 108 after implementation of procedure standardization. Procedure standardization was associated with reductions in length of stay from a mean (SD) of 3.34 (1.79) to 2.46 (1.61) days (difference, 0.88 days; 95% CI, 0.33-1.42 days; P = .002), length of stay in ICU from a mean (SD) of 1.32 (0.69) to 0.99 (0.90) nights (difference, 0.33 nights; 95% CI, 0.06-0.60 nights; P = .02), 30-day readmission rate from 14% (8 patients) in the prestandardization cohort to 5% (5 patients) (difference, 9%; 95% CI, 19.6%-0.3%; P = .03), while extent of resection and intraoperative complication rates were similar between both cohorts. The standardized protocol was associated with mean (SD) savings of $7088.80 ($12 389.50) and decreases in 1-year mortality (dominant intervention). This protocol was found to be cost saving in 75.5% of all simulations in probability sensitivity analysis. Conclusions and Relevance: In this economic evaluation of standardization of awake craniotomy, there was a generalized reduction in length of stay, ICU admission time, and direct medical costs with implementation of an optimized protocol. This was achieved without compromising patient outcomes and with similar extent of resection, complication rates, and reduced readmission rates.

From the Operating Room to the Laboratory: Role of the Neuroscience Tissue Biorepository in the Clinical, Translational, and Basic Science Research Pipeline.

OBJECTIVE: To establish a neurologic disorder-driven biospecimen repository to bridge the operating room with the basic science laboratory and to generate a feedback cycle of increased institutional and national collaborations, federal funding, and human clinical trials. METHODS: Patients were prospectively enrolled from April 2017 to July 2022. Tissue, blood, cerebrospinal fluid, bone marrow aspirate, and adipose tissue were collected whenever surgically safe. Detailed clinical, imaging, and surgical information was collected. Neoplastic and nonneoplastic samples were categorized and diagnosed in accordance with current World Health Organization classifications and current standard practices for surgical pathology at the time of surgery. RESULTS: A total of 11,700 different specimens from 813 unique patients have been collected, with 14.2% and 8.5% of patients representing ethnic and racial minorities, respectively. These include samples from a total of 463 unique patients with a primary central nervous system tumor, 88 with metastasis to the central nervous system, and 262 with nonneoplastic diagnoses. Cerebrospinal fluid and adipose tissue dedicated banks with samples from 130 and 16 unique patients, respectively, have also been established. Translational efforts have led to 42 new active basic research projects; 4 completed and 6 active National Institutes of Health-funded projects; and 2 investigational new drug and 5 potential Food and Drug Administration-approved phase 0/1 human clinical trials, including 2 investigator initiated and 3 industry sponsored. CONCLUSION: We established a comprehensive biobank with detailed notation with broad potential that has helped us to transform our practice of research and patient care and allowed us to grow in research and clinical trials in addition to providing a source of tissue for new discoveries.

Transient Neuropathic Pain Following Mechanically Assisted Manipulation of the Spine: A Clinical Case Study.

We describe the case of a patient developing acute neuropathic pain in the sciatic nerve distribution following spinal manipulation. Manipulative treatment with an Activator Adjusting Instrument (AAI) was recommended and performed. Within 24 hours, the patient developed severe 10/10 pain originating from the left gluteal area at the site of one of the activator deployments with radiation all the way down his left leg to the foot. He was able to maintain distal left leg strength and sensation. Relief was achieved with subsequent physical therapy techniques to relax his deep gluteal muscles, raising the hypothesis of temporary injury to the deep gluteal muscles, with painful contractions resulting in gluteal region pain as well as sciatic nerve inflammation as the nerve passed through that region. This clinical case illustrates some of the perils and risks of spinal manipulation, particularly in the elderly, and the need for careful patient selection.

Hybrid Minimally Invasive Endoscopic Approach for Gaseous Protrusion Causing L5 Radiculopathy.

We present an illustrative case of a hybrid approach between minimally invasive and endoscopic spine surgery techniques. We utilized this hybrid approach for the first 3 cases to help diminish the learning curve as we started a spinal endoscopy program. The patient is an 85-year-old woman with a prior history of arthrodesis at L3-5. She presented with severe leg pain and imaging evidence of degenerative disk disease with disk protrusion in the extraforaminal zone at L5-S1. Computed tomography imaging shows the disk protrusion to be gaseous in nature. Given failure of conservative management and patient refusal for extension of her prior fusion, she was offered a combined minimally invasive navigated technique and endoscopic approach for far lateral diskectomy. After obtaining the correct trajectory, with confirmation by intraoperative fluoroscopy, microscopic visualization was used to identify the protruded disk and the exiting nerve root (Video 1). Given the difficult visualization, a 30-degree endoscopic probe was used, which enabled real-time visualization of the gaseous protrusion being released in the liquid medium. After decompression, microscopic visualization was used for confirmation, with the patient obtaining a good surgical outcome and complete relief of her presenting pain. This case illustrates the synergism between endoscopic and minimally invasive spine surgery techniques and the unique advantages of enabling visualization of spinal anatomy through a liquid medium with the use of an endoscope.1-3.