Publications by authors named "Joshua D Bernstock"

Glioblastoma (GBM) is a highly aggressive brain tumor, associated with hypercoagulability and thrombosis. Tumor Treating Fields (TTFields), a non-invasive therapy that uses low-intensity, alternating electric fields to disrupt cancer cell division, prolongs survival when used concomitantly with radiochemotherapy. TTFields-treated patients often exhibit distinct recurrence patterns, suggesting a local interaction between TTFields and tumor-associated coagulation, underlying mechanisms remain unclear.

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Importance: A 2024 US study reported that veterans of the Iraq and Afghanistan wars affected by traumatic brain injury (TBI) had an increased risk of developing brain tumors. However, studies among civilians have shown conflicting results and have not replicated the association between TBI and brain tumor risk.

Objective: To examine whether history of TBI in US adult civilians is associated with a risk of subsequent development of malignant brain tumors.

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The RNA medicine revolution has been spurred by lipid nanoparticles (LNPs). The effectiveness of an LNP is determined by its lipid components and their ratios; however, experimental optimization is laborious and does not explore the full design space. Computational approaches such as deep learning can be greatly beneficial, but the composite nature of LNPs limits the effectiveness of existing single molecule-based algorithms to LNPs.

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ObjectiveMechanical thrombectomy (MT) is well-established for the treatment of acute ischemic stroke (AIS) from large vessel occlusion (LVO), with growing data supporting the expansion to distal and medium vessel occlusions (DMVO). Despite successful recanalization in DMVO, certain patients still experience poor long-term clinical outcomes, prompting our study to comprehensively explore pre-MT factors influencing outcome despite excellent recanalization (final modified Thrombolysis in Cerebral Infarction [mTICI] score ≥2c).MethodsWe retrospectively examined data from patients who consecutively underwent MT for a primary middle cerebral artery (MCA) DMVO across 37 centers in North America, Asia, and Europe.

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Glial fibrillary acidic protein (GFAP) is an emerging biomarker for the detection of acute intracranial pathology following acute brain injuries such as traumatic brain injury (TBI), stroke, and hypoxic-ischaemic encephalopathy. We undertake a proof-of-concept technical assessment of a commercial lateral flow test (LFT) for the detection of GFAP [the Upfront DX LVOne GFAP lateral flow assay (LFA)], against GFAP concentrations measured using a gold-standard assay [Single Molecule Arrays (Simoa®)-based Human Neurology 4-Plex B assay] in a TBI population. The ability of the LVOne GFAP LFA for identification of samples with GFAP concentrations above the manufacturer's reported lower limit of detection (≥ 0.

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Background: Meningioma is the most common primary CNS tumor, with high-grade cases exhibiting aggressive behavior, frequent recurrence, and poor prognosis. Currently, no systemic therapies are approved for recurrent or malignant meningiomas. Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in hematologic malignancies and promise for solid tumors but its use for meningiomas has been underexplored.

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Background: Years of Life Lost (YLL) is a disease burden measure quantifying the number of years lost due to premature mortality for a given disease. The present study sought to assess YLL for primary brain and other central nervous system (CNS) tumor histopathologies in the United States.

Methods: Mortality, incidence, and life expectancy data for mortalities occurring in 2018 were obtained from the National Vital Statistics System and the National Program of Cancer Registries.

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Reversible contraceptives empower women to prevent unintended pregnancies and enable family planning. However, the need for frequent dosing with pills or injections often leads to suboptimal medication adherence and reduced effectiveness-an issue common to many chronic conditions. Long-acting drug delivery implants offer a compelling alternative by enabling autonomous, multi-year drug release, thereby improving real-world adherence and treatment outcomes.

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BackgroundEndovascular therapy (EVT) for stroke due to distal or medium vessel occlusion (DMVO) is safe. Due to the distinct anatomical characteristics of DMVOs, further evaluation of EVT is crucial to determine which devices may yield better outcomes.MethodsA retrospective analysis of adults with DMVO treated in 37 centers (11 countries) was queried.

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Neuronal-glioma interactions are increasingly recognized as critical in the development and progression of central nervous system tumors. Recent research highlights that gliomas can integrate into neural circuits through various mechanisms, including the synaptogenic factor thrombospondin-1 (TSP-1). This new mechanistic understanding of cancer neuroscience allows for novel insights into target discovery.

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Background And Objectives: Grade 2 meningiomas are associated with variable rates of local recurrence, and the role of adjuvant radiation therapy (RT) remains debated.

Methods: This was a multi-institutional retrospective cohort study including all adult patients with newly diagnosed and previously untreated grade 2 meningioma treated at Mass General Brigham hospitals from 2006 to 2020. Cox proportional-hazards modeling was used to analyze the impact of adjuvant RT on progression-free survival (PFS).

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: Hydrogen peroxide (HO) is a well-known hemostatic and antiseptic agent in neurosurgical practice. While there are concerns regarding the use of HO due to its potential for neuronal damage, the pathophysiological effect on neuronal cells is not clearly understood. : An online survey concerning the use of HO was conducted in a board-certified platform, and an experimental study was designed to investigate the effect of HO on neuronal and tumor cells.

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Implantable systems for neurological chronotherapy are poised to revolutionize the treatment of central nervous system diseases and disorders. These devices enable precise, time-controlled drug delivery aligned with the body's circadian rhythms, optimizing therapeutic outcomes. By bypassing the blood-brain barrier, they achieve high local drug concentrations while minimizing systemic side effects, offering significant advantages for conditions where traditional therapies often fall short.

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Purpose: Recently, the temporalis muscle thickness on cranial CT scan was proposed as a surrogate marker for patients' baseline frailty that correlates with outcome in primary and metastatic brain tumor patients. In this study, we investigated whether the velocity of temporalis muscle atrophy (TMA) affects the outcome of patients with cerebral metastases.

Methods: We analyzed radiological and clinical data sets of 96 patients who received craniotomy for cerebral metastasis resection in our institution.

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Neuroinflammation plays a crucial role in traumatic brain injury (TBI), contributing to both damage and recovery, yet no effective therapy exists to mitigate central nervous system (CNS) injury and promote recovery after TBI. In the present study, we found that nasal administration of an anti-CD3 monoclonal antibody ameliorated CNS damage and behavioral deficits in a mouse model of contusional TBI. Nasal anti-CD3 induced a population of interleukin (IL)-10-producing regulatory T cells (T cells) that migrated to the brain and closely contacted microglia.

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Background And Objectives: The purpose of this systematic review was to provide a comprehensive overview of the available literature on 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX (PpIX) fluorescence-guided surgery (FGS) for the resection of brain metastases (BMs).

Methods: A comprehensive search of the PubMed database for literature on 5-ALA use in BMs surgery was performed. For inclusion, BMs studies had to have data on the observed intraoperative fluorescence available.

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Article Synopsis
  • This study investigates the effects of pre-stroke low-dose aspirin on patients with acute ischemic stroke due to distal medium vessel occlusion undergoing mechanical thrombectomy.
  • Findings show that aspirin users had significantly better functional outcomes and lower mortality rates after treatment, with no increase in bleeding risks.
  • The results suggest that pre-stroke low-dose aspirin could be beneficial and safe for these patients, highlighting the need for more research on this topic.
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Introduction: Mechanical thrombectomy (MT) efficacy in medium vessel occlusion (MeVO) stroke, particularly in patients with low Alberta Stroke Program Early Computed Tomography Score (ASPECTS), remains less explored.

Methods: This retrospective study analyzed data from 443 AIS patients treated with MT for MeVO and low ASPECTS (4-7) at 37 centers across North America, Asia, and Europe, from September 2017 to July 2021. Patients were categorized into ASPECTS of 4-5 and 6-7.

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Article Synopsis
  • Adoptive cell therapy (ACT) with retrovirally transduced T cells and TriVax vaccination shows promise in boosting antitumor immune responses by expanding specific T cell populations.
  • Stat5, a transcription factor, is crucial for T cell proliferation and differentiation, and the study investigates engineered CD8 T cells with active STAT5 in combination with TriVax.
  • Results demonstrate that CA-STAT5 enhances T cell expansion, functional capabilities, and reduces exhaustion, leading to a stronger antitumor effect in melanoma models by inhibiting the PD-1/PD-L1 pathway.
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Significance: Accurate identification between pathologic (e.g., tumors) and healthy brain tissue is a critical need in neurosurgery.

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The development of novel therapeutics in the field of spinal neurosurgery faces a litany of translational challenges. Achieving precise drug targeting within the confined spaces associated with the spinal cord, canal and vertebra requires the development of next generation delivery systems and devices. These must be capable of overcoming inherent barriers related to drug diffusion, whilst concurrently ensuring optimal drug distribution and retention.

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Article Synopsis
  • CPA meningiomas are challenging to treat due to their location near vital nerves and blood vessels, leading to potential postoperative complications and unpredictable recovery outcomes.
  • A study of 95 patients at Mass General Brigham found that common symptoms included hearing loss, ataxia, and headaches, with gross total resection achieved in 62.1% of cases, which was more likely with smaller tumors and when the internal auditory canal was drilled.
  • Post-surgery, most patients experienced stable or improved hearing, but 25.3% showed tumor progression or recurrence, with lower odds of progression linked to complete resection grades and older age.
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Background: Despite the proven effectiveness of endovascular therapy (EVT) in acute ischemic strokes (AIS) involving anterior circulation large vessel occlusions, isolated posterior cerebral artery (PCA) occlusions (iPCAo) remain underexplored in clinical trials. This study investigates the comparative effectiveness and safety of EVT against medical management (MM) in patients with iPCAo.

Methods: This multinational, multicenter propensity score-weighted study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe.

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Background And Purpose: Progression-free survival (PFS) remains to be validated as an outcome measure for diffuse WHO grade 2 gliomas, and knowledge about the relationships between PFS, post-progression survival (PPS), and overall survival (OS) in this subset of tumors is limited. We sought to assess correlations between PFS and OS, and identify factors associated with PFS, PPS, and OS in patients treated for diffuse supratentorial WHO grade 2 gliomas.

Material And Methods: We included 319 patients from three independent observational cohorts.

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