bluuebunny/crossref_metadata_2025_split huggingface dataset:
361 The Frailty-Driven Predictive Model for Failure to Rescue After Cervical Decompression and Fusion: An ACS-NSQIP Analysis of 3,632 Cases (2011-2020)
Authors: Covell Michael , Rumalla Kranti , Rumalla Kavelin , Kassicieh Alex James , Roy Joanna , Kazim Syed Faraz , Skandalakis Georgios P. , Bowers Christian 
Published: March 2024

INTRODUCTION:
Cervical decompression & fusion (CDF) outcome prognostication relies on preoperative risk factors to predict complications and outcomes in order to help guide pre- and perioperative decision-making.

METHODS:
CDF cases were queried from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database 2011-2020. Patients who underwent CDF and experienced a major complication were identified. Within this cohort, FTR was calculated as death or hospice within 30 days of a major complication. Frailty was measured by the Risk Analysis Index-Revised (RAI-Rev). Demographics and baseline characteristics of patients were compared by FTR. Significant factors were assessed by univariate and multivariable regression for the development of a frailty-driven predictive model for FTR. The discriminative ability of the predictive model was assessed using a receiving operating characteristic curve analysis.

RESULTS:
There were 3,632 patients who suffered a major complication from CDF, and 7.6% (277 patients) experienced FTR. Independent predictors of FTR were non-elective surgery, frailty status, preoperative intubation, thrombosis or embolism complication, unplanned intubation, prolonged ventilator use (>48 hours), cardiac arrest, and septic shock. Frailty, and a combination of preoperative and postoperative risk factors in a predictive model for FTR achieved outstanding discriminatory accuracy (C-statistic = 0.901, CI: 0.883-0.919).

CONCLUSIONS:
Preoperative and postoperative risk factors yield a highly accurate predictive model for FTR in CDF patients. Our model may guide surgical management and/or prognostication following the development of a major complication. Future studies may determine the predictive ability of this model in other neurosurgical patient populations. Our predictive model may be deployed by-the-beside here: https://nsgyfrailtyoutcomeslab.shinyapps.io/FailureToRescueCervicalFusion/
362 Enhanced Measures to Quantify Gait and Balance Impairment in Degenerative Cervical Myelopathy: A Prospective Cohort Study
Authors: Perez Tess , Soufi Khadija , Balatbat Patricia , Martin Allan R. 
Published: March 2024

INTRODUCTION:
Gait and balance impairment are among the cardinal symptoms of Degenerative Cervical Myelopathy, however, utilizing objective measurements of these functions is highly challenging.

METHODS:
A prospective cross-sectional cohort study with manual and quantitative gait/balance testing using a Protokinetics Zeno Walkway electronic pressure mat (self/fast-paced, tandem gait/stance, Romberg, one foot standing).

RESULTS:
95 DCM and 78 healthy subjects were included. For quantitave gait assesment, Velocity (p = 4.56x 10-8, 3.39x10-7), Gait Variability Index (p = 1.788x10-8, p = 0.00169), and stability ratio, single stance time/ double stance time, (p = 4.167x10^-7, p = 1.438x10^-5) were significantly different between groups for both self and fast-paced gait assessments, respectively. Balance was assessed by the variability of the center of pressure (COP). The standard deviation variability of COP in both the X (p = 0.00171) and Y directions (p = 0.000104) and cadence (p = 0.00175) were significant for tandem gait, walking heel-to-toe. Standing on either the Left or Right foot also showed a difference in the variability of COP in both directions X (p = 4.21x10^-7 Left Foot, p = 8.27x10^-7 Right Foot) and Y (p = 6.64x10^-4 Left Foot, p = 1.32x10^-4 Right Foot). On, manual assesment, DCM patients scored significantly worse in all parameters such as self-paced (p = 5.54x10^-2), fast-paced (p = 6.28x10^-2), tandem gait (p = 3.60x10^-8), Romberg eyes open (p = 1.58x10^-2), Romberg eyes closed (p = 1.90x10^-2), L foot stance (p = 6.78x10^-6), R foot stance (2.1x10^-6), and tandem stance (p = 8.83x10^-5).

CONCLUSIONS:
Quantitative parameters from an electronic pressure mat can be used to assess gait and balance impairment with high sensitivity and strong correlation with subjective measures. Manual scoring of tandem gait, standing on one foot, and tandem stance also provided robust differences and can be easily adopted into routine assessment of DCM patients.
364 Traumatic Dens Fracture Patients Comprise Distinct Subpopulations Distinguished by Differences in Age, Sex, and Injury Mechanism and Severity
Authors: Cloney Michael Brendan , Roumeliotis Anastasios , Thirunavu Vineeth , Texakalidis Pavlos , Swong Kevin , El Tecle Najib , Dahdaleh Nader S. 
Published: March 2024

INTRODUCTION:
Dens fractures are an increasingly common cervical fractures, yet their epidemiology and its implications remain under-examined.

METHODS:
We retrospectively analyzed all traumatic dens fracture patients managed at our institution over a ten year period with respect to demographic, clinical, and outcomes data. Patient subsets were compared across these parameters.

RESULTS:
303 traumatic dens fracture patients were identified, who showed a bimodal age distribution with strong goodness of fit centered at age 22.3 ± 5.7 (R = 0.8781) and at 77.7 ± 13.9 (R = 0.9686). A population pyramid demonstrated a bimodal distribution among male patients, but not among female patients, which was confirmed with a strong goodness of fit for two distinct male patient subpopulations age <35 (R = 0.9791) and age =35 (R = 0.8843), but a weak fit for a second female subpopulation age <35 (24.5 ± 14.2, R = 0.5957). Patients age <35 were more likely to be male (82.4% vs. 46.9%, OR = 5.29 [1.54, 17.57], p = 0.0052). Moreover, patients age <35 were more likely to have MVC as their mechanism of injury (64.7% vs. 14.1%, OR = 11.18 [3.77, 31.77], p < 0.0001), were more likely to have a severe trauma injury severity score (17.6% vs. 2.9%, OR = 7.23 [1.88, 28.88], p = 0.0198). There was no difference with respect to underlying fracture morphology, likelihood of undergoing surgery, having concomitant atlas or subaxial fractures, or Nurick scores at presentation. Patients age <35 were less likely to have fracture nonunion at follow (18.2% vs. 53.7%, OR = 0.19 [0.041, 0.76], p = 0.0288).

CONCLUSIONS:
The dens fracture patient population comprises two subpopulations, distinguished by differences in age, sex, and injury mechanism and severity, with male dens fracture patients demonstrating a bimodal age distribution. While young patients were more likely to high-energy injury mechanisms leading severe trauma, they were less likely to have fracture nonunion at follow up.
369 Camptocormia in Parkinsons Disease: Systematic Review of Management Using Spine Surgery
Authors: Khan Ali Saif , Nandoliya Khizar Rehan , Mattei Tobias A. , Mercier Philippe , Cloney Michael Brendan , Dahdaleh Nader S. , Koski Tyler R. , El Tecle Najib 
Published: March 2024

INTRODUCTION:
Postural instability or deformity manifests in a variety of ways for a Parkinson's disease (PD) patient, including the classical stooped posture, as well as antecollis, pisa syndrome, degenerative scoliosis, and a debilitating forward flexion of the trunk termed camptocormia. Camptocormia was first described in the midst of World War 1, where young soldiers were found to have a non-fixed forward-bent trunk attributed to the stress of battle.

METHODS:
PubMed was queried for studies involving spine surgery as treatment of PD-associated camptocormia. Studies that described nonsurgical management, deep brain stimulation (DBS), repetitive tran-spinal magnetic stimulation (rTSMS), or were descriptive in nature were excluded.

RESULTS:
The screening process resulted in 5 studies that reported on the use of spine surgery in PD-associated camptocormia. The total number of patients was 19, 12 of which experienced hardware failure warranting revision surgery (63.1%). Clinical and radiologic improvement was inconsistent. Patient outcomes were ultimately satisfactory, only after high reoperation and complication rates.

CONCLUSIONS:
Evidence for the feasibility of spine surgery as management for PD-associated camptocormia is lacking in the literature. In this particular patient population, these procedures carry a high risk of complications and subsequent revision operations, which may negatively affect long-term quality of life. In the absence of or resistance to conservative management, DBS, or rTSMS, spine surgery may be the only option for some patients. Continued investigation via longitudinal and large-scale studies is crucial in order to provide definitive recommendations and treatment algorithms for providers to adhere to.
373 Modified 5-Item Frailty Index: A Useful Tool for Assessing the Impact of Frailty on Postoperative Morbidity and Mortality Following Surgical Fixation of Thoracolumbar Fractures
Authors: Taghlabi Khaled , Santosh Bhenderu Lokeshwar Sai , Guerrero Jaime , Tahanis Aboud , Cruz-Garza Jesus , Faraji Amir H. 
Published: March 2024

INTRODUCTION:
The modified 5-item frailty index (mFI-5) is a comorbidity-based risk stratification tool that has been shown to predict adverse events following various neurological surgeries.

METHODS:
The 2011-2021 American College of Surgeons - National Surgical Quality Improvement Program (ACS-NSQIP) dataset was used to identify patients undergoing fusion surgeries for thoracolumbar spine fractures. The mFI-5 score was calculated based on the presence of the 5 comorbidities: congestive heart failure, diabetes mellitus, chronic obstructive pulmonary disease, partially dependent or totally dependent functional health status, and hypertension. Multivariate analysis was used to assess the independent impact of increasing mFI-5 score on postoperative 30-day morbidity and mortality while controlling for baseline clinical characteristics.

RESULTS:
A total of 66,904 patients were included in our analysis (54.2% female, mean age 62.27 ± 12.93 years). On univariate analysis, higher mFI-5 score was significantly associated with increased risks of superficial surgical site infection(SSI), deep SSI, wound dehiscence, unplanned reoperation, pneumonia, unplanned intubation, postoperative ventilator use, progressive renal insufficiency, acute renal failure, urinary tract infection, stroke, myocardial infarction, cardiac arrest, pulmonary embolism, deep vein thrombosis, bleeding requiring transfusion, sepsis, septic shock, and longer hospital length of stay (LOS). On multivariate logistic regression, increasing mFI-5 score versus mFI-5 = 0 was associated with higher odds of overall complications (mFI-5 =2: odds ratio [OR] 1.44 CI: 1.35–1.52, p < 0.001; mFI-5 = 1: OR 1.18 CI: 1.12–1.24, p < 0.001) and 30-day mortality (mFI-5 =2: OR 2.32 CI: 1.60–3.37, p < 0.001).

CONCLUSIONS:
This study demonstrates that frailty, when measured using the mFI-5, independently predicts postoperative complications, hospital LOS, and 30-day mortality after surgical repair of thoracolumbar fractures. These findings are important for risk stratification in patients undergoing thoracolumbar fusion surgery and for standardization in reporting outcomes after those procedures.
376 Laser Interstitial Thermal Therapy for Deep-Seated Perivascular Brain Tumors: Evaluating the Risk of Distal Ischemia
Authors: Reese Jared C. , Samir Mariam , Fadel Hassan Ali , Pawloski Jacob Andrew , Haider Sameah A. , Robin Adam M. , Kalkanis Steven N. , Lee Ian Yu 
Published: March 2024

INTRODUCTION:
Laser interstitial thermal therapy (LITT) is a novel minimally invasive cytoreductive treatment option for primary and metastatic brain tumors. By relying on stereotactic guidance, the use of LITT carries a risk for direct and thermal vascular injury, especially when targeting deep-seated tumors with surrounding critical vasculature. It is thought that nearby blood vessels act as heat sinks from thermal injury, however, the risk of ablation causing an ischemic stroke is not well reported.

METHODS:
A retrospective review identified patients who underwent LITT between 2013 – 2021 for brain tumors located within the insula, basal ganglia, and thalamus. Demographic, clinical, and volumetric characteristics were collected. The primary outcome was radiographic evidence of distal ischemia on post-ablation imaging.

RESULTS:
A total of 50 patients underwent 59 ablations for perivascular brain tumors located in the insula (52%), basal ganglia (24%), and thalamus (24%). Of the tumors treated, 22 (37%) were low-grade gliomas, 32 (54%) were high-grade gliomas, and 5 (8%) were metastatic. No coagulopathies were identified in any patient. A biopsy was performed in 72% of patients. The mean volume of ablation was 12.4 cm3 (S.D. 13.9) with a median extent of ablation of 92% (IQR 30%, 100%). Two patients developed symptomatic intracerebral hemorrhage. One developed a tract hemorrhage attributed to vessel injury from fiber insertion. The other presented with delayed onset hemorrhage one week later due to uncontrolled hypertension. In all patients, there was no radiographic evidence of distal ischemia following LITT on DWI sequencing . The median length of stay was 2 days with 81% of patients being discharged home.

CONCLUSIONS:
We demonstrate that LITT has minimal risk for new onset distal ischemia for deep-seated perivascular brain tumors.
377 CDKN2A Alterations Are Associated With Increased Postoperative Seizure Risk After Resection of Brain Metastases
Authors: Cummins Daniel Dighton , Garcia Joseph , Nguyen Minh , Saggi Satvir , Chung Jason , Goldschmidt Ezequiel , Berger Mitchel S. , Theodospoulos Philip , Chang Edward , Daras Mariza , Hervey-Jumper Shawn L. , Aghi Manish Kumar 
Published: March 2024

INTRODUCTION:
Seizures are common and significantly disabling for patients with brain metastases (BMs). While surgical resection can provide seizure control, a subset of patients with BMs may continue to suffer seizures postoperatively. Molecular BM characteristics may influence which patients are at-risk for postoperative seizures.

METHODS:
All patients underwent BM resection at one institution with available clinical and sequencing data on > 500 oncogenes. Clinical seizures were documented preoperatively and postoperatively. Random forest machine learning classification was used to determine candidate genomic alterations associated with postoperative seizures, and clinical and top genomic variables were correlated with postoperative seizures using Cox proportional hazards models.

RESULTS:
There were 112 patients with BMs who underwent 114 surgeries and had at least one month of postoperative follow-up. Seizures occurred preoperatively in 26 (22.8%) patients and postoperatively in 25 (21.9%). Engel classification (EC) at six months achieved for those with preoperative seizures was EC I in 13 (50%); II in 6 (23.1%); III in 5 (19.2%), and IV in 2 (7.7%). In those with postoperative seizures, only 8 (32.0%) had seizures preoperatively. Preoperative seizures were not a significant predictor of postoperative seizures (hazards ratio (HR) = 1.84; 95% confidence interval (CI) = 0.79 – 4.37; p = 0.156). On random forest classification and multivariate Cox analysis controlling for factors including recurrence, extent of resection, and number of BMs, CDKN2A alterations were associated with postoperative seizures (HR = 3.22; 95% CI = 1.27–8.16; p = 0.014). Melanoma BMs were associated with higher risk of postoperative seizures compared with all other malignancies (HR = 5.23; 95% CI = 1.37–19.98; p = 0.016).

CONCLUSIONS:
CDKN2A alterations and melanoma primary malignancy are associated with increased postoperative seizure risk following resection of BMs. These results may help guide postoperative seizure prophylaxis in patients undergoing resection of BMs.
382 Precision and Individualized Medicine: Quantification of Brain Cancer Cell Invasion in Confined Microfluidic Spaces Predicts Prognosis
Authors: Suarez-Meade Paola Suarez , Ifembi Brent , Teeter Caroline , Brooks Mieu , Figueredo Luisa Fernanda , Altamirano Alice , Schiapparelli Paula , Chaichana Kaisorn L. , Konstantopolous Konstantinos , Quinones-Hinojosa Alfredo 
Published: March 2024

INTRODUCTION:
Clinical prognosis of patients with glioblastoma (GBM) is calculated with clinical scores, extent of resection, molecular markers, and tumor subtypes. However, these are often hampered by patient comorbidities, drug toxicity, and other confounding factors. We designed a confined 3D microfluidic technology based on the brain cytoarchitecture by mimicking the diameters of the perivascular spaces and white matter tracts utilized by GBM to invade.

METHODS:
Patient-derived GBM cell lines (n = 13) were obtained from patients undergoing surgery. After cell culture, the GBM cells’ abilities to migrate and proliferate with MAqCI were evaluated. MAqCI score was calculated via logistic regression. Patients were categorized into low- and high-PFS. Predicted scores were correlated with the clinical status of patients. Cells were treated with gold standard and experimental drugs, and scores were calculated to predict response to treatment.

RESULTS:
MAqCI Predicted PFS with 83% accuracy, 84.6% sensitivity, and 75% specificity and allowed for the classification of short- and long-PFS (*p = 0.035). Survival based on MAqCI scores separated by short-term (n = 5) and long-term (n = 8) PFS, showed a significant difference between groups (**p = 0.002). After treatment with gold-standard therapy, responder patients were identified based on changes in the MAqCI score. RNAseq of highly motile cells isolated from MAqCI allowed for the identification of druggable targets. An FDA-approved antidepressant against the adrenomedullin gene was selected for MAqCI testing. Changes in MAqCI score after treatment allowed for the identification of responder patients.

CONCLUSIONS:
Cell invasion properties are directly correlated with patient prognosis. MAqCI could be utilized clinically as a companion assay for predicting tumor recurrence and selecting drugs for individualized GBM treatment.
383 Epigenetic Potentiation of Anti-tumor Immune Responses Using Viral Mimicry for Gliomas
Authors: Seetharam Deepa , Chandar Jay , Desgraves Jelisah , Govindarajan Vaidya , Mendez Valdez Mynor J. , Ramsoomair Christian , Castro Jesus , Rivas Sarah , Johnson Kory , Zhang Yong , Nath Avindra , Heiss John D. , Shah Ashish H. 
Published: March 2024

INTRODUCTION:
Human endogenous retroviruses (HERVs) account for approximately 8% of our genome and are evolutionary relics of a germline retroviral infection. Although normally silenced by a master epigenetic regulator, np220, HERVs may be re-expressed in cellular states with marked epigenetic dysregulation and induce innate anti-viral inflammatory responses. This viral mimicry immune response sensitizes tumors to immunotherapy by eliciting double-stranded RNAs (dsRNA)-mediated interferon signaling cascades. Hence, viral mimicry could serve as a predictor of clinical responses to immunotherapy.

METHODS:
We conducted a preclinical study on the role of np220 in GBM and mediating viral mimicry responses.

RESULTS:
Using a tailored bulk transcriptional dataset from 71 newly diagnosed high-grade GBMs, we demonstrated significantly negative correlations between np220 expression and 48 HERV superfamilies. Additionally, using a transcriptional deconvolution pipeline of low-and high-grade gliomas, we demonstrated that np220 is negatively correlated with innate antiviral immune response signatures (TLR3) (RTLR3 = -0.300, pTLR3 = 0.00006). Our in vitro studies have shown that NP220 knockdown induces intracellular HERV-mediated dsRNA-signaling cascades via RIG-1 and TLR3. NP220 knockdown exponentially increases PD-L1 expression (p-value: <0.001), and, increases cytoplasmic accumulation of cellular endogenous dsRNA in established human and mouse glioma cell lines which may induce the interferon-mediated response. This response was recapitulated in recurrent GBM samples with radiographic responses to checkpoint inhibition (anti-PD1) with widely increased expression of dsRNA, PD-L1 and perivascular CD8 cell infiltration, suggesting dsRNA-signaling may mediate response to immunotherapy. Furthermore, we showed np220 is linked to reduced immune cell infiltration (CD8, Dendritic Cells) in the glioma microenvironment through deconvolution of RNA-seq data from TCGA (RCD8 = -.202, RDC = -0.198) (pCD8 = 8.79E-06, pDC = 1.34E-05).

CONCLUSIONS:
Our findings suggest that np220 could serve as a target to potentiate glioma ICI for immune response.
390 Modelling Glioma Associated Macrophages Using Human Embryonic Stem Cell Derived Microglia
Authors: Hopland Kelsey , Hei Yu Kenny Kwok , Mrad Zaki Abou , Torckenczy Kristof , Bander Evan D. , Tabar Viviane S. 
Published: March 2024

INTRODUCTION:
Glioma associated macrophages/microglia (GAMs) are the most abundant immune cell type in glioblastoma and play a key role in immunotherapeutic resistance. The tumor microenvironment (TME) is thought to modulate GAM phenotype and function leading to a more pro-tumorigenic immune milieu however the exact nature of this crosstalk is unclear. Existing systems to study human GAMs are suboptimal as primary human GAMs are difficult to culture. There is therefore a need to develop human model systems of sufficient fidelity to probe GAM function. Here we report on the development of a human embryonic stem cell (hES)-based platform to derive microglia without recourse to immortalizing oncogenic transduction. This technology can assess the impact of tumor derived factors on the microglial phenotype and represents a novel, scalable model system to investigate GAM function.

METHODS:
hES-microglia were generated using a stepwise cytokine-based differentiation protocol. Upon exposure to conditioned media obtained from cultures of a panel of patient-derived glioblastoma cell lines (n=6 biological replicates), hES-GAMs were analyzed using flow cytometry, single cell RNA sequencing (scRNA). Functional assays included phagocytosis of pH rhodo particles, wound scratch migration assays and intracellular proteome analysis.

RESULTS:
Exposure to tumor media leads to transcriptional changes similar to those seen in primary GAMs with increased chemotactic genes such as CCL2(MCP1), CCL3 and CCL4, with corresponding changes in cytokine profile at the protein level. Other upregulated cytokines of note include VEGF, OSM, CCL4 and IL10RB. Functional impact of co-culture with tumor media included a dramatic increase in GAM motility (>30 fold) and a statistically significant decrease in phagocytic ability (29.1% p < 0.001).

CONCLUSIONS:
The hES-derived GAM model is a promising novel platform to dissect the impact of the TME on tumor-derived GAMs.