bluuebunny/crossref_metadata_2025_split huggingface dataset:
348 Risk of Rupture and Treatment Outcomes of Giant Pediatric Aneurysms: Multi-Institutional Case Series and Meta-Meta-Analysis
Authors: Gupta Saksham , Hauser Blake Marie , Catapano Joshua , Farhadi Dara , Smith Edward R. , Lawton Michael T. , Du Rose 
Published: March 2023

INTRODUCTION:
Giant pediatric aneurysms are vascular malformations that can cause significant neurologic morbidity and mortality. Their rarity has precluded large cohort studies to inform their management.

METHODS:
Multi-institutional cohort study of cases from Boston Children’s Hospital (BCH) and the Barrow Neurologic Institute (BNI) along with systematic review and meta-analysis of previously reported cases.

RESULTS:
A total of 15 patients were included in the multi-institutional cohort, and an additional 88 patients were included from 14 series to yield 103 patients within the meta-analysis. Amongst the BCH patients, male sex was associated with giant size (OR .2; 95% CI 1.2-162.0).The most common aneurysm locations were in the MCA (38%), ICA (25%), vertebral artery (VA; 11%), and VBJ (8%). Within 69 reports containing radiographic data within the meta-analysis, 38% of aneurysms were saccular. Twenty-eight cases presented with rupture (28%). 0% of cavernous ICA aneurysms, 26% of other anterior circulation aneurysms, and 44% of posterior circulation aneurysms presented with rupture. Increasing age (OR 1.2; 95% CI 1.0-1.4) and saccular morphology (OR 5.3, 95% CI 1.5-18.9) were associated with presentation with rupture, while posterior location trended towards an association (OR 3.1, 95% CI 0.9-11.0). The majority of cases in the systematic review were treated (97%) rather than observed (3%). Endovascular and open treatments were utilized in 40 and 56% of cases. Survival was 97% for unruptured aneurysms and 82% for ruptured aneurysms. A favorable neurologic outcome occurred in 80% of unruptured cases and 54% of ruptured cases. Unruptured presentation (OR 3.7, 95% CI 1.3-11.1) and endovascular treatment modality were associated with a favorable outcome (OR 5.0; 95% CI 1.6-15.8).

CONCLUSIONS:
Giant pediatric aneurysms are unlikely to be discovered incidentally and often merit treatment. Increasing age and saccular morphology are r predict rupture, and should elevate the concern for semi-urgent treatment.
355 Robotic and Navigated Pedicle Screws Are Safer and More Accurate than Freehand Screws: A Systematic Review and Meta-Analysis
Authors: Matur Abhijith V. , Duah Henry , Palmisciano Paolo , Chilakapati Sai , Cheng Joseph S. , Adogwa Owoicho 
Published: March 2023

INTRODUCTION:
Navigation and robotic pedicle screw placement systems have been developed to improve the accuracy of screw placement. However, the literature comparing the safety and accuracy of robotic and navigated screw placement with freehand screw placement in thoracolumbar spine surgery has been limited.

METHODS:
PubMed and EMBASE were systematically searched according to PRISMA guidelines. The search included indexed terms and text words from database inception to the date of the search (April 7th, 2022). Only randomized controlled trials comparing robotic assisted or navigated screws with fluoroscopic freehand screws in the thoracolumbar spine were included. Data and estimates were pooled using random-effects meta-analysis. Risk of bias was assessed using the Joanna Briggs Institute risk of bias tool. The main outcome measures were odds ratio estimates for screw accuracy according to the Gertzbein-Robbins scale and relative risk for various complications.

RESULTS:
A total of 14 papers encompassing 12 randomized controlled trials were identified. The pooled analysis demonstrated that robotic and navigated pedicle screw placement techniques were associated with increased odds of screw accuracy (OR 2.66, 95% CI 1.24-5.72, p = 0.0118). Robotic and navigated screw placement was associated with a lower risk of facet joint violations (RR 0.09, 95% CI 0.02-0.38, p = 0.0011) and major complications (RR 0.31, 95% CI 0.11-0.84, p = 0.0215). No differences were found in nerve root injury (RR 0.50, 95% CI 0.11-2.30, p = 0.3704), return to the operating room for screw revision (RR 0.28, 95% CI 0.07-1.13, p = 0.0744).

CONCLUSIONS:
These analyses suggest that robotic and navigated screw placement techniques are associated with higher odds of screw accuracy and superior safety profile compared to freehand techniques. Additional randomized controlled trials will be needed to further validate these findings.
361 Awake Spinal Fusion Leads to Decreased Postoperative Opioid Use and Decreased Length of Stay Compared to General Anesthesia: A Matched Cohort Study
Authors: Sykes David , Tabarestani Troy , Chaudhry Nauman Shaukat , Berger Miles , Ayoub Chakib , Gadsden Jeffrey , Gupta Dhanesh Kumar , Shaffrey Christopher I. , Abd-El-Barr Muhammad M. 
Published: March 2023

INTRODUCTION:
Over the past several years, there has been increasing interest in performing spinal fusion under awake spinal anesthesia (SA) as an alternative to general anesthesia (GA). The evidence supporting its use has been positive, albeit limited.

METHODS:
The authors performed a retrospective review of a single surgeon’s patients who underwent lumbar interbody fusions under SA vs GA. Each SA patient was compared to a demographically-matched GA counterpart undergoing a comparable procedure by parametric T-tests. Analyzed outcomes include operative time, opioid usage in morphine milligram equivalents (MME), time to ambulation (TTA), and length of stay (LOS).

RESULTS:
8 SA patients were matched to 8 GA counterparts; the cohort had a mean age of 66.8, a mean BMI of 26.4, and a mean American Society of Anesthesiologists Physical Status (ASA-PS) of 2.81. GA and SA patients demonstrated no statistically significant differences in age, BMI, or ASA-PS. All patients received erector spinae plane blocks with 1.3% liposomal bupivacaine. Postoperative opioid use was reduced in SA patients compared to GA patients (18.86 vs 54.34 MME, p = 0.026). SA patients also demonstrated a shorter hospital LOS (0.52 vs 2.63 days, p = 0.029). SA patients did not demonstrate a statistically significant reduction in procedure duration (138 vs 169 minutes, p = 0.207) nor a statistically significantly reduced TTA (3.85 vs 31.33 hours, p = 0.092).

CONCLUSIONS:
These preliminary retrospective results suggest the use of SA rather than GA for lumbar fusions is associated with lower opioid utilization and reduced hospital length of stay. Future randomized prospective studies are warranted to determine if SA usage truly leads to these beneficial outcomes.
365 Awake Spine Surgery for Traditionally Poor Surgical Candidates: An Illustrative Cohort
Authors: Sykes David , Tabarestani Troy , Chaudhry Nauman Shaukat , Berger Miles , Ayoub Chakib , Gadsden Jeffrey , Gupta Dhanesh Kumar , Shaffrey Christopher I. , Abd-El-Barr Muhammad M. 
Published: March 2023

INTRODUCTION:
Annually, hundreds of thousands of patients undergo surgery for degenerative spine disease (DSD). This represents only a fraction of patients that present for surgical consideration. Procedures are often avoided due to comorbidities that make patients poor candidates for general anesthesia (GA) and its associated risks. With increasing interest in awake surgery under spinal anesthesia (SA), the authors have observed that SA may facilitate spine surgery in patients with relative contraindications to GA.

METHODS:
Case logs of a single surgeon were reviewed, and patients undergoing spine surgery with SA were identified. Within this group, patients were selected that were only able to receive surgery under SA due to their relative contraindications to GA. For this final cohort, the medical records were consulted to report demographic information, as well as patient outcomes.

RESULTS:
8 patients were identified who were only able to receive lumbar spine surgery for DSD under SA due to their relative contraindications to GA. Comorbidities included octogenarian status, obesity, and chronic health conditions such as Parkinson’s and ischemic heart disease. The cohort was 25% female with a mean age of 72.9, a mean BMI of 30.1 kg/m2, and a mean ASA score of 3.0. The average procedure duration was 142.13 minutes. Mean time to ambulation was 23.18 hours and the average hospital length of stay was 1.67 days. The patients used an average of 28.69 morphine milligram equivalents for pain control in the operative and postoperative days.

CONCLUSIONS:
For patients with symptomatic, refractory DSD and relative contraindications to GA, SA may facilitate safe surgical intervention with excellent outcomes.
371 Activated PPARβ/QKI Signaling in Macrophage/Microglia Sensitizes Glioblastoma to Immunotherapy
Authors: Zeng Ailiang , Hu Jian 
Published: March 2023

INTRODUCTION:
Glioblastomas (GBMs) share overwhelmingly immunosuppressive tumor microenvironments that are enriched in glioblastoma-associated macrophages and microglia (GAMs). Notably, GAMs have distinctive reshuffling of lipid composition and dysfunctional lipid metabolism. The peroxisome proliferator-activated receptor (PPAR) family members are master regulators of lipid metabolism in macrophages. One of the PPARs, PPARβ is a pivotal modulator of lipid metabolism in macrophages that orchestrates timely disposal of GBM cells.

METHODS:
Co-immunoprecipitation using an anti-Qki antibody was followed by detecting PPARβ. PPARβ and QKI levels were compared between GAMs inside GBMs and paired macrophages/microglia outside GBMs, as well as human low-grade versus high-grade gliomas. Survival was collected from CX3CR1-CreERT2; PpardL/L/Qki+/+ mice (PPARβ KO) (Ppard is the gene name for PPARβ), CX3CR1-CreERT2; Ppard+/+/QkiL/L mice (QKI KO) and control CX3CR1-CreERT2; Ppard+/+/Qki+/+ (Ctrl) mice given tamoxifen when implanted with GL261 cells. Survival was collected for GBM bearing mice given PPARβ agonist, KD3010 and/or anti-PD-1 therapy.

RESULTS:
PPARβ co-activates the QKI-mediated complex, which is an essential mediator of phagocytosis in macrophage/microglia. Moreover, PPARβ/QKI signaling is markedly decreased in GAMs relative to paired macrophages/microglia within boundary brain parenchyma (P < 0.001). Myeloid cell–specific PPARβ; or QKI knockout shorten overall survival of GBM–bearing mice (P < 0.05), and inhibited PPARβ/QKI signaling in GAMs correlates with grade progression in human gliomas (P < 0.01) and worse prognosis for GBM (P = 0.0034). Therapeutically, PPARβ agonist plus anti-PD-1 greatly prolongs survival of mice GBMs relative to anti-PD-1 monotherapy (P < 0.05).

CONCLUSIONS:
We characterize dysfunctional lipid metabolism in GAMs and elucidates the mechanism underlying immunosuppression of GAMs caused by PPARβ/QKI loss. The study supports for therapeutic options for restoring PPARβ/QKI-mediated lipid metabolism in GAMs and development of novel strategies to sensitize GBM to immunotherapy.
374 Cell Cycle as a Biological Marker of Aggressiveness and Therapeutic Target in Meningiomas
Authors: Lombardi Ismael , Zanini Marco Antonio , Ferrasi Adriana Camargo , Clara Carlos Afonso , Vieira Reis Rui Manuel , Feijó Adriane 
Published: March 2023

INTRODUCTION:
Meningiomas are the most common intracranial tumors, accounting for 36% of cases. The World Health Organization (WHO) classifies these tumors into three histological grades: benign (grade I), atypical (grade II) and anaplastic (grade III). Although most lesions are benign, the treatment that is currently widely recommended is restricted to surgery and/or radiotherapy, which are often insufficient for aggressive lesions or lesions that involve neurovascular structures, making the treatment of meningiomas a challenge even today. The understanding of molecular changes in meningiomas may contribute to the identification of aggressiveness markers and possible new therapeutic targets.

METHODS:
The expressions of approximately 800 genes were evaluated, using the PanCancer Nanostring Kit, in 17 meningiomas (6 benign, 6 atypical and 5 anaplastic) and 6 control arachnoids. Comparisons of gene expression between samples of different histological grades and between tumor and control arachnoid samples were performed and the results tabulated in heatmaps after analysis by bioinformatics tools (NSolver, R Statistics, and DAVID, ROSALIND and COSMIC online databases).

RESULTS:
The molecular cell cycle pathway has components upregulated in the three grades of meningiomas analyzed and significantly induced in histologically more aggressive meningiomas. Hyper-regulated genes may be candidates for markers of aggression. In addition, cell cycle induction can be a therapeutic target in more aggressive meningiomas, with the introduction of cell cycle blocking drugs.

CONCLUSIONS:
The hyper-regulated cell cycle pathway may be associated with aggressiveness in meningiomas. Cell cycle induction in meningiomas can be a therapeutic target for the treatment of these tumors, through cell cycle blockers. Additional studies are needed to corroborate the findings of this study.
379 Human Endogenous Retrovirus-K (HML-2) Contributes to a Unique Stem-Cell Niche in Glioblastoma
Authors: Shah Ashish Harish , Rivas Sarah , Doucet-Ohare Tara , Govindarajan Vaidya , DeMarino Catherine , Ampie Leonel , Banasavadi-Siddegowda Yeshavanath , Maric Dragan , Suter Rob , Lee Myoung-hwa , Zaghloul Kareem A. , Walbridge Stuart , Garcia-Montojo Marta , Steiner Joe , Johnson Kory , Gilbert Mark R. , Heiss John D. , Nath Avindra 
Published: March 2023

INTRODUCTION:
Human Endogenous Retrovirus (HERV) are ancestral viral relics that comprise nearly 8% of the human genome. Although silenced in normal tissues, the most recently integrated provirus HERV-K (HML-2) can be pathologically reactivated in certain cancers.

METHODS:
We utilized a combination approach using scRNA-seq, multiplex immunofluorescence, and TEM to characterize HERV-K expression in malignant gliomas. Using CRISPR engineering and CHIP-qPCR, we downregulated HML-2 in both patient-derived glioma neurospheres and intracranial orthotopic models and identified interactions between HERV-K and pluirpotency transcription factors.

RESULTS:
We identified pathological expression of HML-2 in human malignant gliomas in CSF (HERV-K DNA/RPP30 = 35.2 ± 8.8 vs 23.1 ± 6.7, n = 18, p = 0.02) and tumors (HERV-K RNA/HPRT mean = 1.15 ± 0.2 vs. 0.5 ± 0.2, p = 0.01, n = 20) compared to epilepsy controls. Aberrant HML-2 expression corresponded to a unique stem-cell niche using multivoxel automated segmentation. Using a tailored scRNA-seq sequencing pipeline, we identified glioblastoma cellular populations with elevated HML-2 transcripts in neural progenitor-like cells that can drive cellular plasticity (ANOVA, p < 0.001). Using CRISPR technology, we demonstrate that HML-2 is critical to maintenance of glioblastoma stemness and tumorigenesis in both glioblastoma neurospheres and intracranial orthotopic murine models (OS: 26 days vs. 18.6, p=0.0008, n=20). Downregulation of HERV-K using CRISPRi reduces the glioblastoma neurosphere formation (2-way ANOVA, p < 0.0001) and HERV-K env, Polymerase, OCT4 and Nestin transcripts (2-way ANOVA p < 0.001). Moreover, using Transmission Electron Microscopy, we discovered that some glioma stem-cells form immature retroviral virions in glioblastoma.
Inhibiting HML-2 expression with nucleoside reverse transcriptase inhibitors reduces extracellular reverse transcriptase (One-way ANOVA, p < 0.05), tumor viability (IC50 = 75.8-123.1 uM), and pluripotency (1-way ANOVA, p < 0.01).

CONCLUSIONS:
Our results suggest that HML-2 is overexpressed in the glioblastoma stem-cell niche. Since persistence of glioblastoma stem-cells is considered responsible for treatment resistance/recurrence, HML-2 may serve as a unique therapeutic target in glioblastoma.
384 Characterization of Ex Vivo and In Vivo Intraoperative Neurosurgical Confocal Laser Endomicroscopy Imaging
Authors: Xu Yuan , Abramov Irakliy , Mignucci-Jiménez Giancarlo , Koskay Grant , Belykh Evgenii , Park Marian , Eschbacher Jennifer , Preul Mark C. 
Published: March 2023

INTRODUCTION:
The new FDA-cleared fluorescein sodium (FNa)-based confocal laser endomicroscopy (CLE) imaging system allows for intraoperative on-the-fly cellular level imaging. Two feasibility studies have been completed with intraoperative use of this CLE system in ex vivo and in vivo modalities.

METHODS:
Images acquired from two prospective CLE clinical studies, one ex vivo and one in vivo, were analyzed quantitatively. Two image quality parameters – brightness and contrast – were measured using Fiji software and compared between ex vivo and in vivo images for imaging timing from FNa dose and in glioma, meningioma, and intracranial metastatic tumor cases. The diagnostic performance of the two studies was compared.

RESULTS:
Overall, the in vivo images have higher brightness and contrast than the ex vivo images (p < 0.001). A weak negative correlation exists between image quality and timing of imaging after FNa dose for the ex vivo images, but not the in vivo images. In vivo images have higher brightness and contrast than ex vivo images acquired after FNa redosing. In vivo images have higher image quality than ex vivo images (p < 0.001) in glioma, meningioma, and intracranial metastatic tumor cases. In vivo imaging yielded higher sensitivity (90% vs. 72%) and negative predictive value (81% vs 38%) than ex vivo imaging.

CONCLUSIONS:
In our setting, in vivo CLE optical biopsy outperforms ex vivo CLE by producing higher quality images and less image deterioration, leading to better diagnostic performance. These results support the in vivo modality as the modality of choice for intraoperative CLE imaging.
385 A Cell Resolution Atlas of the Human Cerebrovasculature Reveals Angiogenic and Inflammatory Cell Programs in Arteriovenous Malformations
Authors: Winkler Ethan A. , Kim Chang , Ross Jayden , Garcia Joseph , Gil Eugene , Oh Irene , Chen Lindsay , Wu David , Catapano Joshua , Raygor Kunal P. , Narsinh Kazim , Kim Helen , Weinsheimer Shantel , Cooke Daniel , Walcott Brian Patrick , Lawton Michael T. , Gupta Nalin , Zlokovic Berislav , Chang Edward F. , Abla Adib Adnan , Lim Daniel A. , Nowakowski Tomasz 
Published: March 2023

INTRODUCTION:
Coordinated communications between multiple cell types is responsible for cerebrovascular structure and function. Cellular dysfunction results in cerebrovascular diseases, a leading cause of death and disability. However, we lack a complete census of human cerebrovascular cells necessary to advance understanding of disease mechanisms and therapeutic strategies.

METHODS:
To provide a human cerebrovascular cell atlas, we used single-cell RNA sequencing (scRNAseq) to molecularly profile dissociated vascular cells isolated from the adult human brain and AVMs. Joint comparative analyses profiled patterns of aberrant gene expression in AVMs and resolved cell states enriched in AVMs that bled. Results were validated with fluorescent in situ hybridization, immunostaining, and in vitro functional assays

RESULTS:
By performing scRNAseq on 181,388 single-cells, we identified > 40 molecularly-defined vascular or neighboring cell states from the human cerebrovasculature and AVMs. We identified endothelial molecular signatures underlying arteriovenous phenotypic changes known as “zonations.” Our study uncovered an expanded diversity of perivascular cells unique to humans. In AVMs, there was a loss of normal arteriovenous molecular patterning characterized by the emergence of an endothelial cell state with heightened angiogenic potential and immune cell cross-talk within the AVM nidus. We characterized the cellular ontology of cerebrovascular-derived immune cell response and identified infiltration of distinct immune cell states, such as GPNMB+ monocytes, which deplete stabilizing smooth muscle cells in AVMs that bled.

CONCLUSIONS:
Our single-cell atlas highlighted the heterogeneity underlying cell function and interaction in the human cerebrovasculature and defined molecular and cellular perturbations in AVMs, a leading cause of stroke in young people. The identified interplay between vascular and immune cells will aid development of therapeutics targeting angiogenic and inflammatory programs in vascular malformations.
388 Percutaneous Transluminal Angioplasty and/or Stenting for the Treatment of Basilar Artery Stenosis: A Systematic Review and Meta-Analysis
Authors: Palmisciano Paolo , Hoz Samer Saad , Algburi Hagar A. , Ventre Giancarlo Javier , Street Seth , Agyeman Nana , Robinson Michael , Smith Matthew , Shirani Peyman , Grossman Aaron W. , Prestigiacomo Charles J. 
Published: March 2023

INTRODUCTION:
Basilar artery stenosis (BAS) carries high morbidity and mortality, with variable outcomes reported after endovascular treatments.

METHODS:
PubMed, EMBASE, Web-of-Science, Scopus, and Cochrane were searched upon the PRISMA guidelines to include studies describing PTAS for BAS. Pooled rates of intervention-related complications and outcomes were analyzed with random-effect model meta-analyses.

RESULTS:
We included 25 studies comprising 1016 patients. Patients were mostly male (79.5%), with hypertension (81.1%) and/or dyslipidemia (56.4%), and presenting with transient ischemic attack (54.4%) or stroke (45.6%). BAS frequently involved the middle basilar artery (51.4%), and were mostly classified as Mori-B (57.4%). PTAS for BAS was indicated in patients with severe (≥50%-70%) symptomatic BAS refractory to dual antiplatelet therapy. Patients underwent angioplasty (95.5%) and/or stenting (92.2%), preferably using Wingspan or Apollo stents. Median baseline BAS was 81% (range, 53%-99%), while median post-intervention BAS was 13% (0%-75%). Actuarial rates of successful intervention and “good” final outcome were 100% (95% CI: 100%-100%) and 89% (95% CI: 85%-93%). Intervention-related recurrent ischemic stroke occurred in 85 patients (8.3%) with actuarial rates of 5% (95% CI: 4%-7%), and was differentiated into perforator (5.4%), in-stent (2.6%), and embolic (0.4%). Actuarial rates of intervention-related dissection, restenosis, and death were 0% (95% CI: 0%-0%), 1% (95%CI: 0%-1%), and 0% (95% CI: 0%-2%).

CONCLUSIONS:
Elective PTAS is safe and effective in selected patients with medically-refractory, severe, symptomatic, and non-acute BAS. Different stent types and angioplasty-assisted procedures should be considered based on specific clinico-radiological characteristics of the lesions.