Rapid tumor DNA analysis of cerebrospinal fluid accelerates treatment of central nervous system lymphoma.

ABSTRACT: 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 cause. Participants underwent genotyping of CSF-derived DNA using a quantitative polymerase chain reaction-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 of 33 cases (21.2%) of newly diagnosed neoplasms, resulting in significantly accelerated initiation of disease-directed treatment (median, 3 vs 12 days; P = .027). This assay was then implemented in a Clinical Laboratory Improvement Amendments environment, with 2-day median turnaround for diagnosis of CNS lymphoma from 66 patients across 4 clinical sites. Our study prospectively demonstrates that targeted rapid CSF genotyping influences oncologic management for suspected CNS tumors.

A rapid genotyping panel for detection of primary central nervous system lymphoma.

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.

Clinical Prediction Modeling in Intramedullary Spinal Tumor Surgery.

Artificial intelligence is poised to influence various aspects of patient care, and neurosurgery is one of the most uprising fields where machine learning is being applied to provide surgeons with greater insight about the pathophysiology and prognosis of neurological conditions. This chapter provides a guide for clinicians on relevant aspects of machine learning and reviews selected application of these methods in intramedullary spinal cord tumors. The potential areas of application of machine learning extend far beyond the analyses of clinical data to include several areas of artificial intelligence, such as genomics and computer vision. Integration of various sources of data and application of advanced analytical approaches could improve risk assessment for intramedullary tumors.

Assessment of the efficacy of teriparatide treatment for osteoporosis on lumbar fusion surgery outcomes: a systematic review and meta-analysis.

Treatment of osteoporosis with medications like teriparatide, a parathyroid hormone, is known to improve bone density and reduce the risk of osteoporotic vertebral fractures. Anecdotal and limited surgical series have described the utility of this treatment for osteoporotic patients prior to spinal fusion surgery, but there is variability in adoption of this strategy as well as consensus regarding optimal treatment duration before and after surgery. In this study, the clinical results of the use of teriparatide for this application are reviewed and critically examined. We conducted a systematic review of electronic databases using different MeSH terms from 1980 to 2020. Pooled and subgroup analyses were performed using fixed and random effect models based upon the heterogeneity (I2). The results were reported as either mean difference (MD) or odds ratio (OR) with 95% confidence interval (CI). A total of 771 patients from 12 studies were identified. Three hundred seventy-seven patients (90.8% females) were treated with teriparatide. Lumbar spinal fusion rates were significantly higher among patients who received teriparatide compared to the non-teriparatide group (OR 2.15, 95%CI 1.56-2.97, p < 0.00001). Subgroup analysis revealed that patients receiving teriparatide demonstrated 2.12-fold and 2.23-fold higher likelihood of fusion compared to those in the bisphosphonate (OR 2.12, 95%CI 1.45-3.11, p = 0.0001) and placebo (OR 2.23, 95%CI 1.22-4.08, p = 0.009) cohorts, respectively. The treatment effect of teriparatide was associated with significantly reduced subsequent vertebral fractures (OR 0.16, 95%CI 0.06-0.41, p = 0.0002), sagittal malalignment (MD - 3.85, 95%CI: -6.49 to - 1.21, p = 0.004), limb visual analogue score (VAS) (MD - 0.36, 95%CI - 0.64 to - 0.09, p = 0.008), and spinal VAS (MD - 0.24, 95%CI - 0.44 to - 0.04, p = 0.02) compared to the non-teriparatide group. Patients using teriparatide had 30% less likelihood of screw loosening at last follow-up compared to the non-teriparatide group; however, this was not statistically significant (OR 0.70, 95%CI 0.43-1.14, p = 0.15). There did not exist any statistically significant difference between the two comparative groups in terms of pseudoarthrosis (OR 0.54, 95%CI 0.24-1.21, p = 0.13), cage subsidence (OR 1.30, 95%CI 0.38-4.52, p = 0.68), and bone mineral density (MD 0.04, 95%CI - 0.19-0.29, p = 0.74) at last follow-up examination. This meta-analysis corroborates the effectiveness of teriparatide resulting in higher fusion rates. Further study is required to determine the optimal duration of treatment and timing of surgery.

Advances in surgical hemostasis: a comprehensive review and meta-analysis on topical tranexamic acid in spinal deformity surgery.

Tranexamic acid (TXA) is an effective and commonly used hemostatic agent for perioperative blood loss in various surgical specialties. It is being increasingly used in spinal deformity surgery. We aimed to evaluate the safety and efficacy of topical TXA (tTXA) compared to both placebo and/or intravenous (IV) TXA in patients undergoing spinal deformity surgery. We conducted a systematic review of the electronic databases using different MeSH terms from January 1970 to August 2019. Pooled and subgroup analysis was performed using fixed and random-effect model based upon the heterogeneity (I2). A total of 609 patients (tTXA: n = 258, 42.4%) from 8 studies were included. We found that there was a statistically significant difference in terms of (i) postoperative blood loss [mean difference (MD) - 147.1, 95% CI - 189.5 to - 104.8, p < 0.00001], (ii) postoperative hemoglobin level (MD 1.09, 95% CI 0.45 to 1.72, p = 0.0008), (iii) operative time (MD 7.47, 95% CI 2.94 to 12.00, p < 0.00001), (iv) postoperative transfusion rate [odds ratio (OR) 0.39, 95% CI 0.20 to 0.78, p = 0.007], postoperative drain output (MD, - 184.0, 95% CI - 222.03 to - 146.04, p < 0.00001), and (v) duration of hospital stay (MD - 1.14, 95% CI - 1.44 to - 0.85, p < 0.00001) in patients treated with tTXA compared to the control group. However, there was no significant difference in terms of intraoperative blood loss (p = 0.13) and complications (p = 0.23) between the two comparative groups. Furthermore, low-dose (250-500 mg) tTXA (p < 0.00001) reduced postoperative blood loss more effectively compared to high-dose tTXA (1-3 g) (p = 0.001). Our meta-analysis corroborates the effectiveness and safety of tTXA in spinal deformity surgery.

Genotype-targeted local therapy of glioma.

Aggressive neurosurgical resection to achieve sustained local control is essential for prolonging survival in patients with lower-grade glioma. However, progression in many of these patients is characterized by local regrowth. Most lower-grade gliomas harbor isocitrate dehydrogenase 1 (IDH1) or IDH2 mutations, which sensitize to metabolism-altering agents. To improve local control of IDH mutant gliomas while avoiding systemic toxicity associated with metabolic therapies, we developed a precision intraoperative treatment that couples a rapid multiplexed genotyping tool with a sustained release microparticle (MP) drug delivery system containing an IDH-directed nicotinamide phosphoribosyltransferase (NAMPT) inhibitor (GMX-1778). We validated our genetic diagnostic tool on clinically annotated tumor specimens. GMX-1778 MPs showed mutant IDH genotype-specific toxicity in vitro and in vivo, inducing regression of orthotopic IDH mutant glioma murine models. Our strategy enables immediate intraoperative genotyping and local application of a genotype-specific treatment in surgical scenarios where local tumor control is paramount and systemic toxicity is therapeutically limiting.

Safety and efficacy of cement augmentation with fenestrated pedicle screws for tumor-related spinal instability.

OBJECTIVE: Achieving rigid spinal fixation can be challenging in patients with cancer-related instability, as factors such as osteopenia, radiation, and immunosuppression adversely affect bone quality. Augmenting pedicle screws with cement is a strategy to overcome construct failure. This study aimed to assess the safety and efficacy of cement augmentation with fenestrated pedicle screws in patients undergoing posterior, open thoracolumbar surgery for spinal metastases. METHODS: A retrospective review was performed for patients who underwent surgery for cancer-related spine instability from 2016 to 2019 at the Massachusetts General Hospital. Patient demographics, surgical details, radiographic characteristics, patterns of cement extravasation, complications, and prospectively collected Patient-Reported Outcomes Measurement Information System Pain Interference and Pain Intensity scores were analyzed using descriptive statistics. Logistic regression was performed to determine factors associated with cement extravasation. RESULTS: Sixty-nine patients underwent open posterior surgery with a total of 502 cement-augmented screws (mean 7.8 screws per construct). The median follow-up period for those who survived past 90 days was 25.3 months (IQR 10.8-34.6 months). Thirteen patients (18.8%) either died within 90 days or were lost to follow-up. Postoperative CT was performed to assess the instrumentation and patterns of cement extravasation. There was no screw loosening, pullout, or failure. The rate of cement extravasation was 28.9% (145/502), most commonly through the segmental veins (77/145, 53.1%). Screws breaching the lateral border of the pedicle but with fenestrations within the vertebral body were associated with a higher risk of leakage through the segmental veins compared with screws without any breach (OR 8.77, 95% CI 2.84-29.79; p < 0.001). Cement extravasation did not cause symptoms except in 1 patient who developed a symptomatic thoracic radiculopathy requiring decompression. There was 1 case of asymptomatic pulmonary cement embolism. Patients experienced significant pain improvement at the 3-month follow-up, with decreases in Pain Interference (mean change 15.8, 95% CI 14.5-17.1; p < 0.001) and Pain Intensity (mean change 28.5, 95% CI 26.7-30.4; p < 0.001). CONCLUSIONS: Cement augmentation through fenestrated pedicle screws is a safe and effective option for spine stabilization in the cancer population. The risk of clinically significant adverse events from cement extravasation is very low.

Performance assessment of the metastatic spinal tumor frailty index using machine learning algorithms: limitations and future directions.

OBJECTIVE: Frailty is recognized as an important consideration in patients with cancer who are undergoing therapies, including spine surgery. The definition of frailty in the context of spinal metastases is unclear, and few have studied such markers and their association with postoperative outcomes and survival. Using national databases, the metastatic spinal tumor frailty index (MSTFI) was developed as a tool to predict outcomes in this specific patient population and has not been tested with external data. The purpose of this study was to test the performance of the MSTFI with institutional data and determine whether machine learning methods could better identify measures of frailty as predictors of outcomes. METHODS: Electronic health record data from 479 adult patients admitted to the Massachusetts General Hospital for metastatic spinal tumor surgery from 2010 to 2019 formed a validation cohort for the MSTFI to predict major complications, in-hospital mortality, and length of stay (LOS). The 9 parameters of the MSTFI were modeled in 3 machine learning algorithms (lasso regularization logistic regression, random forest, and gradient-boosted decision tree) to assess clinical outcome prediction and determine variable importance. Prediction performance of the models was measured by computing areas under the receiver operating characteristic curve (AUROCs), calibration, and confusion matrix metrics (positive predictive value, sensitivity, and specificity) and was subjected to internal bootstrap validation. RESULTS: Of 479 patients (median age 64 years [IQR 55-71 years]; 58.7% male), 28.4% had complications after spine surgery. The in-hospital mortality rate was 1.9%, and the mean LOS was 7.8 days. The MSTFI demonstrated poor discrimination for predicting complications (AUROC 0.56, 95% CI 0.50-0.62) and in-hospital mortality (AUROC 0.69, 95% CI 0.54-0.85) in the validation cohort. For postoperative complications, machine learning approaches showed a greater advantage over the logistic regression model used to develop the MSTFI (AUROC 0.62, 95% CI 0.56-0.68 for random forest vs AUROC 0.56, 95% CI 0.50-0.62 for logistic regression). The random forest model had the highest positive predictive value (0.53, 95% CI 0.43-0.64) and the highest negative predictive value (0.77, 95% CI 0.72-0.81), with chronic lung disease, coagulopathy, anemia, and malnutrition identified as the most important predictors of postoperative complications. CONCLUSIONS: This study highlights the challenges of defining and quantifying frailty in the metastatic spine tumor population. Further study is required to improve the determination of surgical frailty in this specific cohort.

DMD genomic deletions characterize a subset of progressive/higher-grade meningiomas with poor outcome.

Progressive meningiomas that have failed surgery and radiation have a poor prognosis and no standard therapy. While meningiomas are more common in females overall, progressive meningiomas are enriched in males. We performed a comprehensive molecular characterization of 169 meningiomas from 53 patients with progressive/high-grade tumors, including matched primary and recurrent samples. Exome sequencing in an initial cohort (n = 24) detected frequent alterations in genes residing on the X chromosome, with somatic intragenic deletions of the dystrophin-encoding and muscular dystrophy-associated DMD gene as the most common alteration (n = 5, 20.8%), along with alterations of other known X-linked cancer-related genes KDM6A (n =2, 8.3%), DDX3X, RBM10 and STAG2 (n = 1, 4.1% each). DMD inactivation (by genomic deletion or loss of protein expression) was ultimately detected in 17/53 progressive meningioma patients (32%). Importantly, patients with tumors harboring DMD inactivation had a shorter overall survival (OS) than their wild-type counterparts [5.1 years (95% CI 1.3-9.0) vs. median not reached (95% CI 2.9-not reached, p = 0.006)]. Given the known poor prognostic association of TERT alterations in these tumors, we also assessed for these events, and found seven patients with TERT promoter mutations and three with TERT rearrangements in this cohort (n = 10, 18.8%), including a recurrent novel RETREG1-TERT rearrangement that was present in two patients. In a multivariate model, DMD inactivation (p = 0.033, HR = 2.6, 95% CI 1.0-6.6) and TERT alterations (p = 0.005, HR = 3.8, 95% CI 1.5-9.9) were mutually independent in predicting unfavorable outcomes. Thus, DMD alterations identify a subset of progressive/high-grade meningiomas with worse outcomes.

Rapid Neurological Recovery Following Partial Surgical Resection of Spinal Glioblastoma Multiforme in a Pediatric Patient Presenting With Complete Paraplegia.

Pediatric spinal cord glioblastoma multiforme is a rare entity with a poor prognosis often presenting with lower extremity weakness or paralysis. Previous literature suggests that aggressive surgical resection may provide overall survival benefit; however, there is limited concurrent analysis demonstrating neurological recovery following surgical resection. We report the case of a 9-year-old boy who presented with complete paraplegia and regained the ability to ambulate independently following subtotal surgical resection, radiation, and chemotherapy. The case demonstrates the balance between meaningful neurological recovery and overall survival when deciding on the extent of resection in cases of pediatric spinal glioblastoma multiforme.

Secreted amyloid ß-proteins in a cell culture model include N-terminally extended peptides that impair synaptic plasticity.

Evidence for a central role of amyloid ß-protein (Aß) in the genesis of Alzheimer's disease (AD) has led to advanced human trials of Aß-lowering agents. The "amyloid hypothesis" of AD postulates deleterious effects of small, soluble forms of Aß on synaptic form and function. Because selectively targeting synaptotoxic forms of soluble Aß could be therapeutically advantageous, it is important to understand the full range of soluble Aß derivatives. We previously described a Chinese hamster ovary (CHO) cell line (7PA2 cells) that stably expresses mutant human amyloid precursor protein (APP). Here, we extend this work by purifying an sodium dodecyl sulfate (SDS)-stable, ∼8 kDa Aß species from the 7PA2 medium. Mass spectrometry confirmed its identity as a noncovalently bonded Aß40 homodimer that impaired hippocampal long-term potentiation (LTP) in vivo. We further report the detection of Aß-containing fragments of APP in the 7PA2 medium that extend N-terminal from Asp1 of Aß. These N-terminally extended Aß-containing monomeric fragments are distinct from soluble Aß oligomers formed from Aß1-40/42 monomers and are bioactive synaptotoxins secreted by 7PA2 cells. Importantly, decreasing ß-secretase processing of APP elevated these alternative synaptotoxic APP fragments. We conclude that certain synaptotoxic Aß-containing species can arise from APP processing events N-terminal to the classical ß-secretase cleavage site.

Emergence of nanoscale viscoelasticity from single cancer cells to established tumors.

Tumors are complex materials whose physical properties dictate growth and treatment outcomes. Recent evidence suggests time-dependent physical properties, such as viscoelasticity, are crucial, distinct mechanical regulators of cancer progression and malignancy, yet the genesis and consequences of tumor viscoelasticity are poorly understood. Here, using Wide-bandwidth AFM-based ViscoElastic Spectroscopy (WAVES) coupled with mathematical modeling, we probe the origins of tumor viscoelasticity. From single carcinoma cells to increasingly sized carcinoma spheroids to established tumors, we describe a stepwise evolution of dynamic mechanical properties that create a nanorheological signature of established tumors: increased stiffness, decreased rate-dependent stiffening, and reduced energy dissipation. We dissect this evolution of viscoelasticity by scale, and show established tumors use fluid-solid interactions as the dominant mechanism of mechanical energy dissipation as opposed to fluid-independent intrinsic viscoelasticity. Additionally, we demonstrate the energy dissipation mechanism in spheroids and established tumors is negatively correlated with the cellular density, and this relationship strongly depends on an intact actin cytoskeleton. These findings define an emergent and targetable signature of the physical tumor microenvironment, with potential for deeper understanding of tumor pathophysiology and treatment strategies.

Machine learning-based detection of sarcopenic obesity and association with adverse outcomes in patients undergoing surgical treatment for spinal metastases.

OBJECTIVE: The distributions and proportions of lean and fat tissues may help better assess the prognosis and outcomes of patients with spinal metastases. Specifically, in obese patients, sarcopenia may be easily overlooked as a poor prognostic indicator. The role of this body phenotype, sarcopenic obesity (SO), has not been adequately studied among patients undergoing surgical treatment for spinal metastases. To this end, here the authors investigated the role of SO as a potential prognostic factor in patients undergoing surgical treatment for spinal metastases. METHODS: The authors identified patients who underwent surgical treatment for spinal metastases between 2010 and 2020. A validated deep learning approach evaluated sarcopenia and adiposity on routine preoperative CT images. Based on composition analyses, patients were classified with SO or nonsarcopenic obesity. After nearest-neighbor propensity matching that accounted for confounders, the authors compared the rates and odds of postoperative complications, length of stay, 30-day readmission, and all-cause mortality at 90 days and 1 year between the SO and nonsarcopenic obesity groups. RESULTS: A total of 62 patients with obesity underwent surgical treatment for spinal metastases during the study period. Of these, 37 patients had nonsarcopenic obesity and 25 had SO. After propensity matching, 50 records were evaluated that were equally composed of patients with nonsarcopenic obesity and SO (25 patients each). Patients with SO were noted to have increased odds of nonhome discharge (OR 6.0, 95% CI 1.69-21.26), 30-day readmission (OR 3.27, 95% CI 1.01-10.62), and 90-day (OR 4.85, 95% CI 1.29-18.26) and 1-year (OR 3.78, 95% CI 1.17-12.19) mortality, as well as increased time to mortality after surgery (12.60 ± 19.84 months vs 37.16 ± 35.19 months, p = 0.002; standardized mean difference 0.86). No significant differences were noted in terms of length of stay or postoperative complications when comparing the two groups (p > 0.05). CONCLUSIONS: The SO phenotype was associated with increased odds of nonhome discharge, readmission, and postoperative mortality. This study suggests that SO may be an important prognostic factor to consider when developing care plans for patients with spinal metastases.

Sub-Internship Academy: Implementation and Evaluation of Single-Day Resident-Driven Focused Sub-Internship Preparation Course.

OBJECTIVE: Strong performance in neurosurgical sub-internships is a vital component of a successful residency application and requires adequate familiarity with clinical knowledge and technical skills that may not be covered in standard medical school curricula. Accordingly, a need exists for immersive and comprehensive sub-internship preparation programs that respect time and resource limitations, are optimized based on longitudinal student feedback, provide opportunities for mentorship, and foster enthusiasm for neurosurgery. Therefore, residents at a single institution designed and implemented a comprehensive curriculum for a 1-day sub-internship academy. METHODS: Academy curriculum involved hands-on and discussion-based elements split into 3 workshops. Anonymous surveys were conducted immediately following the academy and upon completion of sub-internships to evaluate participant perceptions on the utility of the academy. RESULTS: Twelve medical students participated in the inaugural neurosurgery sub-internship academy. Nine responded to the immediate postsurvey, which revealed the following ratings: the overall program was rated as having maximal impact on sub-internship readiness and enthusiasm for neurosurgery by 8 (88.9%) and 7 (77.8%) respondents, respectively. A largely positive impact on access to mentorship was observed. Six participants responded to a postsub-internship survey, and all 6 indicated they agreed or strongly agreed that the academy prepared them to perform well. CONCLUSIONS: Student perceptions of the relevance and utility of the sub-internship academy were positive, and the program fostered enthusiasm for neurosurgery and provided opportunities for mentorship. The participants indicated the academy positively impacted their sub-internship performance, and areas for improvement to guide future iterations of the academy were identified.

Disparities in Surgical Intervention and Health-Related Quality of Life Among Racial/Ethnic Groups With Degenerative Lumbar Spondylolisthesis.

BACKGROUND AND OBJECTIVES: Racial and socioeconomic disparities in spine surgery for degenerative lumbar spondylolisthesis persist in the United States, potentially contributing to unequal health-related quality of life (HRQoL) outcomes. This is important as lumbar spondylolisthesis is one of the most common causes of surgical low back pain, and low back pain is the largest disabler of individuals worldwide. Our objective was to assess the relationship between race, socioeconomic factors, treatment utilization, and outcomes in patients with lumbar spondylolisthesis. METHODS: This cohort study analyzed prospectively collected data from 9941 patients diagnosed with lumbar spondylolisthesis between 2015 and 2020 at 5 academic hospitals. Exposures were race, socioeconomic status, health coverage, and HRQoL measures. Main outcomes and measures included treatment utilization rates between racial groups and the association between race and treatment outcomes using logistic regression, adjusting for patient characteristics, socioeconomic status, health coverage, and HRQoL measures. RESULTS: Of the 9941 patients included (mean [SD] age, 67.37 [12.40] years; 63% female; 1101 [11.1%] Black, Indigenous, and People of Color [BIPOC]), BIPOC patients were significantly less likely to use surgery than White patients (odds ratio [OR] = 0.68; 95% CI, 0.62-0.75). Furthermore, BIPOC race was associated with significantly lower odds of reaching the minimum clinically important difference for physical function (OR = 0.74; 95% CI, 0.60; 0.91) and pain interference (OR = 0.77; 95% CI, 0.62-0.97). Medicaid beneficiaries were significantly less likely (OR = 0.65; 95% CI, 0.46-0.92) to reach a clinically important improvement in HRQoL when accounting for race. CONCLUSION: This study found that BIPOC patients were less likely to use spine surgery for degenerative lumbar spondylolisthesis despite reporting higher pain interference, suggesting an association between race and surgical utilization. These disparities may contribute to unequal HRQoL outcomes for patients with lumbar spondylolisthesis and warrant further investigation to address and reduce treatment disparities.

Genetic characterization and mutational profiling of foramen magnum meningiomas: a multi-institutional study.

OBJECTIVE: Foramen magnum (FM) meningiomas pose significant surgical challenges and have high morbidity and mortality rates. This study aimed to investigate the distribution of clinically actionable mutations in FM meningiomas and identify clinical characteristics associated with specific mutational profiles. METHODS: The authors conducted targeted next-generation sequencing of 62 FM meningiomas from three international institutions, covering all relevant meningioma genes (AKT1, KLF4, NF2, POLR2A, PIK3CA, SMO, TERT promoter, and TRAF7). Patients with a radiation-induced meningioma or neurofibromatosis type 2 (NF2) were excluded from the study. Additionally, patient and tumor characteristics, including age, sex, radiological features, and tumor location, were retrospectively collected and evaluated. RESULTS: The study cohort consisted of 46 female and 16 male patients. Clinically significant driver mutations were detected in 58 patients (93.5%). The most commonly observed alteration was TRAF7 mutations (26, 41.9%), followed by AKT1E17K mutations (19, 30.6%). Both mutations were significantly associated with an anterolateral tumor location relative to the brainstem (p = 0.0078). NF2 mutations were present in 11 cases (17.7%) and were associated with posterior tumor location, in contrast to tumors with TRAF7 and AKT1E17K mutations. Other common mutations in FM meningiomas included POLR2A mutations (8, 12.9%; 6 POLR2AQ403K and 2 POLR2AH439_L440del), KLF4K409Q mutations (7, 11.3%), and PIK3CA mutations (4, 6.5%; 2 PIK3CAH1047R and 2 PIK3CAE545K). POLR2A and KLF4 mutations exclusively occurred in female patients and showed no significant association with specific tumor locations. All tumors harboring AKT1E17K and POLR2A mutations displayed meningothelial histology. Ten tumors exhibited intratumoral calcification, which was significantly more frequent in NF2-mutant compared with AKT1-mutant FM meningiomas (p = 0.047). CONCLUSIONS: These findings provide important insights into the molecular genetics and clinicopathological characteristics of FM meningiomas. The identification of specific genetic alterations associated with tumor location, volume, calcification, histology, and sex at diagnosis may have implications for personalized treatment strategies in the future.

Wearable bio-adhesive metal detector array (BioMDA) for spinal implants.

Dynamic tracking of spinal instrumentation could facilitate real-time evaluation of hardware integrity and in so doing alert patients/clinicians of potential failure(s). Critically, no method yet exists to continually monitor the integrity of spinal hardware and by proxy the process of spinal arthrodesis; as such hardware failures are often not appreciated until clinical symptoms manifest. Accordingly, herein, we report on the development and engineering of a bio-adhesive metal detector array (BioMDA), a potential wearable solution for real-time, non-invasive positional analyses of osseous implants within the spine. The electromagnetic coupling mechanism and intimate interfacial adhesion enable the precise sensing of the metallic implants position without the use of radiation. The customized decoupling models developed facilitate the precise determination of the horizontal and vertical positions of the implants with incredible levels of accuracy (e.g., <0.5 mm). These data support the potential use of BioMDA in real-time/dynamic postoperative monitoring of spinal implants.