Glioblastoma (GBM) remains one of the most challenging brain malignancies due to the restrictive nature of the blood-brain barrier (BBB), which severely limits effective drug and gene delivery. To overcome this, we introduce Biodegradable Acoustic Targeting for Ultrasound-Supported Gene Therapy (BATUS), a modular platform that enables safe, repeated, and targeted gene delivery to the brain. BATUS integrates an implantable, fully biodegradable glycine-based ultrasound (US) transducer, surgically placed via craniotomy for precise BBB opening, along with customizable peptide-targeted liposomal gene carriers. This system combines US-mediated transient BBB disruption with ligand-directed cellular targeting to enable efficient delivery across both vascular and cellular barriers. As a proof-of-concept, BATUS was evaluated using tLyp1-functionalized liposomes carrying PD-L1-targeting siRNA for GBM immunotherapy: in vitro evaluations confirmed efficient siRNA entrapment, stability, and specific cellular uptake, while in vivo studies in orthotopic GL261 GBM mouse models showed enhanced BBB permeability, significant PD-L1 silencing, reduced tumor growth, and prolonged survival. Crucially, BATUS exhibited a favorable safety profile, with no detectable local or systemic toxicity in animal models. By providing a modular framework where targeting ligands and genetic cargo are easily adaptable, BATUS is established as a strategy for precision gene delivery across the BBB, as demonstrated here for GBM.

BACKGROUND:Traumatic spinal cord injury (SCI) causes profound and lasting disability. Early neurological recovery, as captured by conversion in American Spinal Injury Association Impairment Scale (AIS) grade, is a key prognostic indicator. While preclinical studies suggest sex-based neuroprotective mechanisms, the impact of biological sex on AIS conversion remains unclear. The objective of this study was to determine whether female sex is independently associated with increased odds of AIS conversion during hospitalization for SCI. METHODS:We conducted a retrospective cohort study using data from the Spinal Cord Injury Model Systems database (2012-2021). Patients with non-missing sex and AIS discharge data were included. The primary exposure was reported sex at admission, and the primary outcome was AIS conversion during hospitalization. Multivariable logistic regression models adjusted for demographic and clinical covariates, including age, mechanism of injury, multiple trauma, spinal surgery, and baseline AIS grade. Sensitivity analyses excluded patients with AIS grade A injuries and those ≥65 years of age. A propensity score-matched analysis was also performed. RESULTS:Among 7,910 patients (median age, 40 years; interquartile range, 26-56 years), 20% were female. Association Impairment Scale conversion occurred in 31% of patients. Female sex was independently associated with higher odds of AIS conversion (odds ratio, 1.23; 95% confidence interval, 1.07-1.42; p  = 0.004). This association remained significant across sensitivity analyses and after propensity score matching (odds ratio, 1.26; 95% confidence interval, 1.09-1.46; p  = 0.002). CONCLUSION:Female sex was independently associated with greater odds of early neurologic recovery after SCI, as measured by AIS conversion. These findings suggest biological or biomechanical differences may influence short-term SCI recovery and underscore the need for sex-informed approaches in SCI research and rehabilitation. ( J Trauma Acute Care Surg . 2026;100: 942-948. Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.). LEVEL OF EVIDENCE:Retrospective Cohort Study; Level III.

BACKGROUND CONTEXT Primary tumors of the cervical and cervicothoracic junction (CTJ) are rare and anatomically constrained; oncologic control often requires en bloc spondylectomy with circumferential reconstruction. Mechanical risk is largely extrapolated from thoracolumbar cohorts and may not reflect CTJ-specific biomechanics. PURPOSE The purpose of this study was to characterize reconstruction strategies and mechanical failure patterns following cervical and cervicothoracic junction en bloc spondylectomy, and to identify exploratory risk signals associated with instrumentation failure in this anatomically and biomechanically distinct region. STUDY DESIGN/SETTING Retrospective cohort study. PATIENT SAMPLE Cervical and cervicothoracic junction spondylectomy patients at Johns Hopkins Hospital (2015–2025). OUTCOME MEASURES Mechanical complications and overall survival. METHODS Single-institution retrospective cohort (2015–2025) of consecutive cervical/CTJ primary tumors treated with en bloc spondylectomy and circumferential reconstruction. Demographics, pathology, construct details, bone quality by Hounsfield units (HU), and oncologic therapies were abstracted. The primary endpoint was instrumentation failure, including any mechanical event prompting or necessitating revision. Univariate analysis was conducted. RESULTS Twenty patients (mean age 49.1 ± 15.3 years; 55% male) were included: chordoma 50%, chondrosarcoma 15%, others 35%. Anterior column reconstruction used a titanium cage in 85%; posterior constructs used 2 rods in 75% (3.5 mm in 65%); CoCr rods in 5%. Instrumentation failure occurred in 3/20 (15%) at 4–44 months (median follow-up nonfailure 30 months, range 1–96; failure 60 months, range 44–94). Failure modes included 2 anterior column events (cage migration or delayed visceral erosion) and one posterior rod fracture. Failure patients more often had smaller (3.5 mm) 2-rod constructs and fewer levels instrumented above the resection; CoCr rod use was enriched among failures (33.3% vs 0%; p = 0.015). Thirty-day readmission was higher with failure (100% vs 17.6%; p = 0.004). HU values trended lower in failures, but no covariate reached significance in univariate analysis. CONCLUSIONS Mechanical complications occurred in 15% of cervical/CTJ spondylectomies, with a notable proportion involving anterior column failure. Although underpowered for definitive predictors, this exploratory analysis identified several risk signals: limited proximal fixation, small-diameter 2-rod constructs, and CoCr rod usage that may inform CTJ-specific reconstruction strategies. These findings support exploring the impact of robust proximal fixation, biologically supported anterior reconstruction, bone-health optimization, and long-term surveillance on mechanical complications in CTJ en bloc spondylectomy of primary spinal tumors. FDA Device/Drug Status This abstract does not discuss or include any applicable devices or drugs.

BackgroundDepression is common among elective lumbar spine surgery candidates and is associated with worse postoperative outcomes. Home-based transcranial direct current stimulation (tDCS) has demonstrated safety and feasibility, with evidence of antidepressant effects in remote randomized and open-label studies of major depressive disorder (MDD). Whether this approach can be feasibly and acceptably implemented as a preoperative intervention in lumbar spine surgical populations is unknown.MethodsWe propose a prospective, open-label, single-arm feasibility study evaluating preoperative, home-based tDCS for elective, non-revision lumbar spine surgery candidates with MDD. Adults aged 22–75 years with DSM-5 MDD and at least moderate depressive symptom severity [self-reported Montgomery–Åsberg Depression Rating Scale (MADRS-S) ≥ 20] being evaluated for elective lumbar spine surgery will receive home-based tDCS. Key exclusion criteria include history of seizure disorder, implanted cranial electronic or metallic devices, clinically unstable psychiatric conditions, prior brain stimulation therapy, and use of medications that significantly affect cortical excitability. Pre-surgical treatment follows a standardized cadence (5 sessions/week for 3 weeks, then 3 sessions/week) for a minimum of 4 weeks, continuing until surgery or up to 10 weeks. Feasibility will be assessed using a pre-specified tiered exposure framework based on the number of sessions completed before surgery.Anticipated resultsPrimary outcomes are feasibility and acceptability of preoperative home-based tDCS delivery. The principal exploratory clinical outcome is change in depressive symptom severity measured using MADRS-S. Exploratory perioperative recovery outcomes include spine-related disability, pain intensity, functional status, and opioid utilization. For participants who proceed to surgery, postoperative outcomes will be followed up to 12 months.DiscussionThis pilot study will generate feasibility, acceptability, and preliminary signal data to inform the design of future randomized controlled trials of preoperative neuromodulation in surgical populations.

OBJECTIVE:Pediatric cervical spinal cord injury (cSCI) is a severe form of trauma with age-dependent anatomical and physiological risks that affect treatment strategies and outcomes. Due to the lack of comprehensive national-level data, this study aimed to evaluate age-specific differences in epidemiology, injury patterns, and clinical outcomes in pediatric patients with traumatic cSCI. METHODS:The authors performed a retrospective analysis using the National Trauma Data Bank (2007-2018) to identify pediatric patients (≤ 18 years old) with traumatic cSCI and stratified them into newborns/infants, toddlers, children, and adolescents. The primary outcome was early mortality. Multivariable logistic regression identified predictors of mortality, complications, and discharge outcomes, adjusting for relevant clinical variables. RESULTS:A total of 4696 pediatric patients with cSCI were identified. While adolescents (71.9%) and children (20.5%) accounted for most cases, newborns/infants and toddlers had higher mortality rates (25.6% and 22.1%, respectively; p < 0.001). Motor vehicle traumas predominated in younger children, whereas firearm injuries were more common in adolescents. Younger groups experienced significantly longer intensive care unit stays, extended ventilator use, and higher complication rates. Toddlers (OR 1.86, p = 0.014), critical injury severity (OR 3.60), and Glasgow Coma Scale (GCS) scores of 3-5 (OR 51.51) were associated with significantly higher odds of death. Greater injury severity and lower GCS scores were also associated with a higher risk of complications. Use of protective devices and venous thromboembolism prophylaxis were associated with lower mortality. CONCLUSIONS:Among pediatric patients with cSCI, infants and toddlers predominantly experienced motor vehicle-related and more severe injury, and worse clinical outcomes, which requires aggressive early management and age-appropriate trauma protocols. In contrast, firearm and recreational injuries were more common among adolescents, reinforcing the necessity of targeted prevention and community education. These findings highlight the importance of age-specific strategies in both clinical care and injury prevention for this high-risk population.

Patients undergoing surgery for spinal metastases often have limited physiologic reserve. Although hypoalbuminemia is a recognized risk marker, its graded association with short-term postoperative outcomes and discharge disposition has not been well defined in large national cohorts. We evaluated the relationship between preoperative serum albumin and early postoperative outcomes following surgery for spinal metastases. Adults undergoing surgery for metastatic extradural spinal tumors (laminectomy or tumor excision with or without fusion) were identified in ACS-NSQIP (2010–2022). Hypoalbuminemia was defined as albumin < 3.5 g/dL and stratified as mild (3.0–3.49), moderate (2.5–2.99), or severe (< 2.5). Primary outcomes were any 30-day complication, 30-day mortality, and non-home discharge. Multivariable logistic regression adjusted for demographic, clinical, and operative factors. Exploratory machine-learning models assessed discrimination and variable importance. Among 4,126 patients, 1,534 (37.2

e14042 Background: Metastatic cancers to the central nervous system (CNS) usually affect the brain. A small but clinically significant proportion also develop intradural spinal disease, though little is known about lesions to this compartment. Here, we characterize the molecular features of intradural spinal disease that spread from non-CNS cancers and describe the metastatic chronology such lesions go through to reach this space. Methods: All patients with MRI spine report findings of intramedullary or leptomeningeal lesions from 2020–2025 at a tertiary academic center were screened for intradural spinal disease. Patients with primary CNS cancer or non-cancer diagnoses were excluded. Demographic information, CSF cytopathology results, imaging characteristics of intradural spinal disease, dates of primary cancer and metastasis detection (CNS and non-CNS sites), and immunohistochemistry and next generation sequencing data of all disease sites were collected wherever available. The primary outcome of interest was overall survival (OS) from date of primary diagnosis. Results: 1401 patients were screened and 69 met inclusion criteria. The most common primary pathologies were lung (23/69, 33.3%) and breast (22/69, 31.9%). 30 (43.5%) patients had lumbar punctures for CSF cytopathology, of which 16 (23.2%) detected tumor cells. 8/69 (11.6%) patients underwent surgery for intradural disease. The distribution of intradural spine disease on initial detection was 38 (55.1%) cervical, 45 (65.2%) thoracic, and 53 (76.8%) lumbar. The mortality rate was 87.0% (60/69) within a median follow-up of 20.6 (IQR 42.0-72.9) months after primary cancer diagnosis. The median time from primary diagnosis to any metastasis was 0.5 (0-6.7), to the brain was 14.9 (0.6-42.7), to the osseous spine was 19.4 (0.7-38.9), and to the intradural spine was 29.5 (14.0-52.6) months. Mutations with common targetable therapeutics were noted in 32/69 (46.4%) primary lesions and patients with such actionable mutations trended towards improved OS (51.7 months, 31.2-105.2) compared to patients without (30.1 months, 12.6-58.9, p=0.072). The molecular profile of the intradural spine lesions were notably different from systemic markers for actionable mutations in 2/8 (25%) cases. Conclusions: Actionable mutations are present in nearly 50% of patients who develop spinal intradural disease, and so regular molecular characterization and sequencing of this space (e.g. CSF liquid biopsy) could have a clinically meaningful impact on these patients. Further, surveillance imaging of patients concerning for spinal intradural disease can miss >25% of intradural spinal disease if MRI of only one part of the spine is regularly imaged.

Intramedullary spinal cord tumors (IMSCTs) pose a high risk of iatrogenic neurologic injury during resection, yet no blood-based assay is available to quantify intra-operative neuroglial damage in real time. A 36-year-old woman with a C7–T3 WHO grade II ependymoma underwent laminoplasty and microsurgical gross total resection. Peripheral blood was collected at five peri-operative time points. Spinal cord-derived cell free DNA was quantified by droplet-digital PCR, and 119-plex proteomics measured four previously validated proteins (FABP-3, REST, IL-6, NF-H). The Spinal Cord Injury Index (SCII)—a dimensionless composite generated from these analytes—was calculated at each time point. SCII increased after initial myelotomy, peaking at myelotomy completion, then returned to pre-myelotomy levels by postoperative day 1. In contrast, glial fibrillary acidic protein and neurofilament-light concentrations were lagging indicators that continued increasing after completion of myelotomy and into postoperative day 1. SCII demonstrated temporal fidelity to the patient’s neurologic trajectory and outcome. SCII may allow for high temporal fidelity, molecular monitoring that parallels surgical manipulation and precedes classical protein biomarker elevations, suggesting potential future utility as a real-time liquid biopsy for spinal-cord monitoring during neurosurgical oncology.

BACKGROUND:Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are aggressive sarcomas often arising in the spine, characterized by high metastatic potential and poor prognosis. While photon radiation therapy (RT) has been employed for local control, the role of proton RT in spinal MPNST remains poorly defined. Our objective is to compare treatment patterns, survival outcomes, and predictors of mortality among spinal MPNST patients treated with photon vs. proton RT. METHODS:This retrospective cohort study utilized the National Cancer Database (2004-2017) to identify patients with spinal MPNST. Demographics, tumor characteristics, treatment details, and outcomes were compared between patients receiving no radiation, photon RT, or proton RT. Survival was assessed using Kaplan-Meier analysis and Cox proportional hazards models. Machine learning-based survival models evaluated predictive performance, feature importance, and SHAP values. RESULTS:Of 5,664 spinal MPNST patients, 3,264 (57.3%) received RT (photon: 97.5%; proton: 2.5%). Proton therapy recipients were younger, had smaller tumors, and more frequently received adjuvant chemoradiation (p < 0.001). Proton therapy was associated with significantly improved 10-year survival (88.5% vs. 73.8%; p = 0.003) and lower long-term mortality (HR: 0.47; p = 0.024). Comorbidity burden, distant metastasis, and high biologically effective dose (BED > 70 Gy) were predictors of both short- and long-term mortality on the multivariate model. The Gradient Boosting model identified BED, CDCC score, and tumor size as the most influential predictors, with a highest AUC for 10-year mortality of 0.715. CONCLUSION:Proton therapy is associated with superior long-term survival compared to photon therapy in spinal MPNST patients, particularly among the subtotal resection cohort. Radiation dose, tumor size, and comorbidity burden are strong predictors of mortality. These findings support the integration of proton therapy into treatment algorithms and emphasize the importance of individualized, risk-adapted strategies to improve survival in patients with spinal MPNST.

Abstract Metastatic cancers to the central nervous system (CNS) usually affect the brain, but a small and clinically significant portion also affect the intradural spinal space. Here, we characterize the molecular features of metastatic intradural spinal disease and describe the metastatic chronology such lesions go through to reach this space. All patients with MRI spine findings of intramedullary or leptomeningeal lesions from 2020–2025 at a tertiary academic center were screened. Patients with primary CNS cancer or non-cancer diagnoses were excluded. Demographic information, imaging findings, dates of primary cancer and metastasis detection, and molecular data across disease sites were collected. The primary outcome of interest was overall survival (OS) after primary diagnosis. 69 patients met inclusion criteria out of 1401 patients screened. The most common primary pathologies were lung (33.3%) and breast (31.9%). 11.6% of patients underwent surgery for intradural disease. The distribution of intradural spine disease on initial detection was 55.1% cervical, 65.2% thoracic, and 76.8% lumbar. The mortality rate was 87.0% within a median follow-up of 20.6 (IQR 42.0-72.9) months. The median time to any metastasis was 0.5 (0-6.7), to the brain was 14.9 (0.6-42.7), to the osseous spine was 19.4 (0.7-38.9), and to the intradural spine was 29.5 (14.0-52.6) months. Targetable mutations were noted in 46.4% of primary lesions and such patients trended towards improved OS (51.7 months, 31.2-105.2) compared to patients without (30.1 months, 12.6-58.9, p = 0.072). Actionable mutations are present in nearly 50% of patients who develop spinal intradural disease, and so regular molecular characterization and sequencing of this space (e.g. CSF liquid biopsy) could have a clinically meaningful impact on these patients. Further, surveillance imaging of patients concerning for spinal intradural disease can miss >25% of intradural spinal disease if MRI of only one part of the spine is regularly imaged.

OBJECTIVE:The purpose of this work is to develop a data-driven framework for real-time prediction of focused ultrasound pressure fields in the spinal cord, addressing the limitations of computationally intensive acoustic simulations. Focused ultrasound therapy offers submillimeter precision for targeted treatment of spinal cord injuries, but its efficacy depends critically on transducer placement due to the spinal cord's complex geometry and acoustic heterogeneity across anatomical layers. METHODS:Conventional computational models rely on wave propagation simulations to generate patient-specific pressure maps, but these can take hours to complete parameter sweeps and are impractical for surgical decision-making. To address this bottleneck, we introduce a vision transformer-based Deep Operator Network (ViT-DeepONet), benchmarked against a convolutional DeepONet (convolutional neural network [CNN]-DeepONet) and a geometry-aware Fourier Neural Operator. By learning the solution operator of the governing partial differential equations, these models generalize across transducer positions and spinal geometries without new simulations. RESULTS:Trained on 8000 simulated pressure maps from porcine spinal cords (n=25), ViT-DeepONet achieves realtime predictions with 3.1% test loss and generalizes to human ultrasound images with 4.4% loss, reducing computation time by more than 91,000-fold relative to central processing unit-based high-fidelity solvers. ViT-DeepONet outperforms CNN-DeepONet (5.1% loss) while using fivefold fewer parameters. A geometry-aware Fourier Neural Operator attains the lowest loss (2.6%), but with eightfold higher complexity. CONCLUSION:ViT-DeepONet accurately captures spatial and geometric dependencies in heterogeneous acoustic domains, enabling real-time ultrasound pressure prediction with a lower computational burden. These results demonstrate the feasibility of operator learning as a powerful framework for accelerating acoustic modeling and optimizing patient-specific therapeutic ultrasound imaging.

Spine oncology patients often experience a multidimensional symptom burden beyond pain. Despite improvements in survival outcomes, changes in patients’ physical and psychosocial domains following spine tumor surgery remains poorly characterized, and minimal clinically important differences (MCIDs) in this complex group have not been established. Patient-Reported Outcomes (PROs) of adult patients undergoing spine tumor surgery between 2023 and 2025 were measured using PROMIS-29 questionnaires. Longitudinal trajectories were described and modeled using linear mixed-effects model. MCIDs were calculated in subpopulations stratified by baseline pain severity. Physical and psychosocial symptoms are heavily interconnected. Pain intensity correlated most strongly with pain interference (ρ = 0.80) and physical function (ρ = 0.54). Patients with high baseline pain (≥ 4) were more likely to achieve MCID despite greater overall symptom burden. Pain improved significantly within 3 months postoperatively; however, it does not synchronously transform into functional improvement. Recovery trajectory varied across domains and subgroups, while a biphasic pattern of early improvement followed by transient worsening that later improved or stabilized was observed across multiple domains. Recovery following spine tumor surgery is domain-specific and dynamic. Baseline pain level delineates both symptom profiles and recovery pattern, which needs to be considered in counseling patients. Multidisciplinary management involving both functional rehabilitation and psychosocial intervention are needed.

CFR-PEEK is an alternative to Titanium-based instrumentation offering reduced artifact and comparable biomechanical properties. However, its clinical outcomes, complication profile, and cost-effectiveness remain underexplored. In this study, we aim to: (1) Evaluate clinical results of patients who underwent surgical decompression and stabilization using CFR-PEEK instrumentation for primary or metastatic spinal tumors; (2) Perform a systematic review summarizing the published literature on CFR-PEEK in spinal oncology, and (3) Present a model for cost-effectiveness analysis of ‘Hybrid’ CFR-PEEK versus titanium instrumentation strategies. We conducted: 1) A retrospective review of patients who underwent surgery for primary/metastatic spinal tumors using ‘Hybrid’ CFR-PEEK/Titanium. We assessed demographics, perioperative characteristics, hardware complications, local recurrence, and mortality. 2) Systematic review of CFR-PEEK instrumentation in spinal oncology. 3) Decision modeling-based economic evaluation comparing cost () and effectiveness (QALYs) of ‘Hybrid’ versus Titanium-only constructs. ICERs were calculated using a150,000/QALY WTP threshold. Twenty-four patients (52.2