Dynamic fibroblast-immune interactions shape recovery after brain injury.

Fibroblasts and immune cells coordinate tissue regeneration and necessary scarring after injury. In the brain, fibroblasts are border-enriched cells whose dynamic molecular states and immune interactions after injury remain unclear. Here we define the shared fibroblast-immune response to brain injury.

An engineered glioblastoma model yields macrophage-secreted drivers of invasion.

While the accumulation of tumor-associated macrophages (TAMs) in glioblastoma (GBM) has been well documented, targeting TAMs has thus far yielded limited clinical success in slowing GBM progression due, in part, to an incomplete understanding of TAM function. Using an engineered 3D hydrogel-based model of the brain tumor microenvironment (TME), we show that M2-polarized macrophages stimulate transcriptional and phenotypic changes in GBM stem cells (GSCs) closely associated with the highly aggressive and invasive mesenchymal subtype. By combining proteomics with GBM patient single-cell transcriptomics, we identify multiple TAM-secreted proteins with putative proinvasive functions and validate TGF-β induced (TGFBI, also known as BIGH3) as a targetable TAM-secreted tumorigenic factor.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for the Role of Imaging for Patients With Functioning Pituitary Adenomas.

Background: Patients with functioning pituitary adenomas (FPA) present a diagnostic challenge with identification of microadenomas and/or invasion of the cavernous sinus.

Objective: The aim of this study was to provide evidence-based recommendations on the use of imaging to facilitate an accurate diagnosis.

Methods: PubMed and Embase were searched from the inception of the database to June 8, 2021, using search terms and search strategies to identify pertinent abstracts.

Factors associated with matching into highly ranked U.S. neurosurgical residencies.

Objective: To identify applicant characteristics independently associated with matching into highly ranked U.S. neurosurgical residency programs.

Functional Gonadotroph Adenomas in Male Patients: Clinical Characteristics, Surgical Outcomes, and Hormonal Follow-up.

Background And Objectives: Functional gonadotroph adenomas (FGAs) are rare pituitary neuroendocrine tumors derived from the steroidogenic factor 1 (SF-1) lineage that present clinically with elevated serum levels of follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH). While previous research has predominantly featured female patients, this study specifically aims to better understand the clinical characteristics and postoperative outcomes of FGAs in male patients.

Methods: A retrospective review of medical records from a single institution, encompassing 1306 pituitary adenomas, identified 12 male patients who underwent transsphenoidal resection for FGAs.

Developmental Plasticity and Stromal Co-option Shape a Pituitary Neuroendocrine Tumor Transcriptional Continuum.

Pituitary neuroendocrine tumors (PitNETs) are common intracranial neoplasms with complex biology underpinned by unresolved cellular origins, molecular heterogeneity, and microenvironment interactions. Here, we employ single-nuclei RNA-sequencing (snRNA-seq) of 419,874 cells from human normal pituitaries and PitNETs with spatial transcriptomics to resolve these challenges. We identify multi-hormonal neuroendocrine cells in both normal and tumor tissues, originating as early pseudotime intermediates from pituitary stem cells, revealing an inherent plasticity that blurs traditional lineage boundaries.

Association of non-English language preference with tumor characteristics and postoperative outcomes following pituitary neuroendocrine tumor resection: a retrospective review of 1143 cases.

Objective: Non-English language preference (NELP) poses a barrier to healthcare access and may contribute to delays in seeking care, understanding treatment plans, and communicating health concerns. This study assesses the relationship between NELP and the clinical characteristics and outcomes of patients with pituitary neuroendocrine tumors (PitNETs) at a high-volume tertiary center.

Methods: A retrospective analysis was conducted on 1143 adult patients who underwent PitNET surgery between 2012 and 2019 at a single institution.

IL-6 underlies microenvironment immunosuppression and resistance to therapy in glioblastoma.

The glioblastoma tumor immune microenvironment (TIME) is an immunosuppressive barrier to therapy that encumbers glioblastoma responses to immune checkpoint inhibition (ICI). Immunosuppressive cytokines, pro-tumor myeloid cells, and exhausted T-cells are hallmarks of the glioblastoma TIME. Here we integrate spatial and single-cell analyses of patient-matched human glioblastoma samples before and after ICI with genetic, immunologic, single-cell, and pharmacologic studies in preclinical models to reveal that interleukin-6 (IL-6) inhibition reprograms the glioblastoma TIME to sensitize mouse glioblastoma to ICI and radiotherapy.

Dynamic fibroblast-immune interactions shape wound healing after brain injury.

Fibroblasts coordinate the response to tissue injury, directing organ regeneration versus scarring. In the central nervous system (CNS), fibroblasts are uncommon cells enriched at tissue borders, and their molecular, cellular, and functional interactions after brain injury are poorly understood. Here we define the fibroblast response to sterile brain damage across time and space.

Association of lower tumor mutation burden with rapid local progression in patients with brain metastases.

Objective: Tumor mutational burden (TMB) has been proposed as a prognostic biomarker in patients with metastatic cancer, as well as in patients who receive immune checkpoint inhibitor (ICI) therapy. However, the role of TMB as a biomarker for progression after resection of brain metastases, as well as perioperative ICI treatment response, is less defined. This study examined the impact of TMB on local CNS progression events in patients who underwent resection of a brain metastasis, as well as in those who received postoperative ICI treatment.

Druggable genome CRISPRi screen in 3D hydrogels reveals regulators of cortactin-driven actin remodeling in invading glioblastoma cells.

To identify new therapeutic targets that limit glioblastoma (GBM) invasion, we applied druggable-genome CRISPR screens to patient-derived GBM cells in micro-dissectible biomimetic 3D hydrogel platforms that permit separation and independent analysis of core vs. invasive fractions. We identified 12 targets whose suppression limited invasion, of which ACP1 (LMW-PTP) and Aurora Kinase B (AURKB) were validated in neurosphere assays.

Focused ultrasound therapy as a strategy for improving glioma treatment.

The infiltrative and diffuse nature of gliomas makes complete resection unfeasible. Unfortunately, regions of brain parenchyma with residual, infiltrative tumor are protected by the blood-brain barrier (BBB), making systemic chemotherapies, small-molecule inhibitors, and immunotherapies of limited efficacy. Low-frequency focused ultrasound (FUS) in combination with intravascular microbubbles can be used to disrupt the BBB transiently and selectively within the tumor and peritumoral region.

Preoperative predictors of biochemical remission in somatotroph adenoma resections: a single-institution retrospective review.

Objective: There is persistent debate in the literature surrounding the true predictors of biochemical remission after resection of somatotroph adenoma. A multimodal analysis of a large number of patients is needed to better understand which patients may be at higher or lower risk for remission failure after surgery.

Methods: A retrospective review was performed on patients undergoing somatotroph adenoma resection.

Viscoelastic High-Molecular-Weight Hyaluronic Acid Hydrogels Support Rapid Glioblastoma Cell Invasion with Leader-Follower Dynamics.

Hyaluronic acid (HA), the primary component of brain extracellular matrix, is increasingly used to model neuropathological processes, including glioblastoma (GBM) tumor invasion. While elastic hydrogels based on crosslinked low-molecular-weight (LMW) HA are widely exploited for this purpose and have proven valuable for discovery and screening, brain tissue is both viscoelastic and rich in high-MW (HMW) HA, and it remains unclear how these differences influence invasion. To address this question, hydrogels comprised of either HMW (1.

A propensity score-matched cost-effectiveness analysis of magnetic resonance-guided laser interstitial thermal therapy versus craniotomy for brain tumor radiation necrosis.

Objective: Radiation necrosis is becoming an increasingly prevalent complication in patients with brain tumors given the growing utility of stereotactic radiosurgery in modern treatment paradigms. Magnetic resonance-guided laser interstitial thermal therapy (MRgLITT) is a new minimally invasive modality that has exhibited an efficacy comparable to craniotomy in treating radiation necrosis. No studies to date have compared their cost-effectiveness despite the significant additional expenses associated with MRgLITT use.

Collagen VI deposition primes the glioblastoma microenvironment for invasion through mechanostimulation of β-catenin signaling.

While glioblastoma (GBM) progression is associated with extensive extracellular matrix (ECM) secretion, the causal contributions of ECM secretion to invasion remain unclear. Here we investigate these contributions by combining engineered materials, proteomics, analysis of patient data, and a model of bevacizumab-resistant GBM. We find that GBM cells cultured in engineered 3D hyaluronic acid hydrogels secrete ECM prior to invasion, particularly in the absence of exogenous ECM ligands.

Glioblastoma induces the recruitment and differentiation of dendritic-like "hybrid" neutrophils from skull bone marrow.

Tumor-associated neutrophil (TAN) effects on glioblastoma (GBM) biology remain under-characterized. We show here that neutrophils with dendritic features-including morphological complexity, expression of antigen presentation genes, and the ability to process exogenous peptide and stimulate major histocompatibility complex (MHC)II-dependent T cell activation-accumulate intratumorally and suppress tumor growth in vivo. Trajectory analysis of patient TAN scRNA-seq identifies this "hybrid" dendritic-neutrophil phenotype as a polarization state that is distinct from canonical cytotoxic TANs, and which differentiates from local precursors.

Acute hyponatremia post craniotomy resulting in a unilateral fixed and dilated pupil: A case study on diagnosis and management.

Background: Postoperative hyponatremia is a known complication of intracranial surgery, which can present with depressed mental status. Hyponatremia resulting in focal neurologic deficits is less frequently described.

Case Description: We describe a patient who, after a bifrontal craniotomy for olfactory groove meningioma, developed acute hyponatremia overnight with a decline in mental status from Glasgow coma scale (GCS) score 15 to GCS 7 and a unilateral fixed dilated pupil.

Viscoelastic high-molecular-weight hyaluronic acid hydrogels support rapid glioblastoma cell invasion with leader-follower dynamics.

Hyaluronic acid (HA), the primary component of brain extracellular matrix, is increasingly used to model neuropathological processes, including glioblastoma (GBM) tumor invasion. While elastic hydrogels based on crosslinked low-molecular-weight (LMW) HA are widely exploited for this purpose and have proven valuable for discovery and screening, brain tissue is both viscoelastic and rich in high-MW (HMW) HA, and it remains unclear how these differences influence invasion. To address this question, hydrogels comprised of either HMW (1.

Glioma Cells Secrete Collagen VI to Facilitate Invasion.

While glioblastoma (GBM) progression is associated with extensive extracellular matrix (ECM) secretion, the causal contributions of ECM secretion to invasion remain unclear. Here we investigate these contributions by combining engineered materials, proteomics, analysis of patient data, and a model of bevacizumab-resistant GBM. We find that GBM cells cultured in engineered 3D hyaluronic acid hydrogels secrete ECM prior to invasion, particularly in the absence of exogenous ECM ligands.