bluuebunny/crossref_metadata_2025_split huggingface dataset:
518 Identification of Tumor Infiltrating Leukocytes in Glioblastoma and Clinical Outcomes
Authors: Orozco Andres Restrepo , Goodyke Austin , Zagorski Joseph , Vitaz Todd 
Published: March 2023

INTRODUCTION:
Glioblastoma (GBM) accounts for 60% of all malignant brain tumors in adults with a dismal 5-year survival rate of 5%. Treatment challenges stem from GBM’s intricate biology, therapy-resistant tumor cells, favorable milieu, invasive properties, and immunosuppressive tumor-infiltrating leukocytes (TIL). These cells are pro-repair and provide an immune inhibitory function, thereby conferring an elusive and protective phenotype to malignant cells. The clinical association with outcomes and response of these cell types to chemotherapeutics remains largely uncharacterized.

METHODS:
Fresh GBM tumor samples were collected. Using flow cytometry, tumor-specific and TIL-specific antibodies are used to label these cells. GBM and TIL phenotype within each sample is correlated to patient outcome to understand how those are related to the successes and failures of treatment. In addition, these cells are subjected to a different chemotherapeutics to assess their response to therapy.

RESULTS:
Patients’ mean age was 66.3 y, 15 patients (62%) were female. There was variable expression of EFGR and PDFRA within and between tumors. TIL represent approximately 20% of the cells in the samples. Myeloid cells represent most TIL (86%) in most samples. MGMT promoter un-methylated status was associated with high proportion of MDSC (34%) and poor survival. Correlations between TIL and GBM immunophenotypes were observed such as an inverse correlation between EGFR expression and MDSCs. Drug-screening is currently underway.

CONCLUSIONS:
The MDSC and EGFR inverse correlation suggests a possible relationship between tumor cells and TIL, supported by studies showing a release of pro-repair cytokines with EGFR signaling. Similarly, T-cells were positively correlated with EGFR expression. These findings strengthen the evidence of the protective role of TIL in GBM. Chemotherapeutics are being currently studied to assess impact on tumor viability.
552 Quantifying the Blood-Brain Barrier in Acute Ischemic Stroke Using Novel MR Imaging
Authors: Mouchtouris Nikolaos , Alizadeh Mahdi , Ailes Isaiah , Piper Keenan , Gooch M. Reid , Tjoumakaris Stavropoula I. , Rosenwasser Robert H. , Wu Chengyuan , Jabbour Pascal 
Published: March 2023

INTRODUCTION:
Acute ischemic stroke causes endothelial cell and tight junction damage, resulting in blood-brain barrier (BBB) disruption. BBB disruption is a significant risk factor for hemorrhagic conversion, which is seen in up to 20-40% of patients, increasing mortality by 7.9-fold. A number of processes, such as reperfusion injury, neuroinflammation, and neoangiogenesis impact the BBB permeability, which can fluctuate for several weeks after stroke. Despite its significance, BBB permeability is not taken into consideration in the management of this patient population.

METHODS:
We used two MRI sequences, diffusion-prepared pseudocontinuous arterial spin labeling (DP-pCASL) and Neurite Orientation Dispersion and Density Imaging (NODDI) to scan patients greater than 18 years old who presented with acute ischemic stroke. DP-pCASL generates cerebral blood flow, arterial transit time (ATT), and BBB permeability. NODDI generates neurite dispersion index (NDI), orientation dispersion index (ODI), and free water index (ISO) maps. Normalized BBB permeability above the 75th percentile of the vascular territories was defined as high permeability.

RESULTS:
Ten patients were enrolled with a mean age of 66.8 ± 13.9 and NIHSS of 15.8 ± 8.0. Patients were scanned at a mean 83.4 ± 78.8 hours from symptom onset. Two patients had received alteplase and 6 patients underwent mechanical thrombectomy. Multivariable logistic regression showed that increasing ATT (p <0.001), decreasing ODI signal (p = 0.001), increasing relative monocyte count (p = 0.001) were significant predictors of increased BBB permeability. Intubation/general anesthesia decreased the odds of high BBB permeability (OR 0.072, p < 0.001).

CONCLUSIONS:
Higher ATT, higher monocyte count, lower ODI, and lack of anesthesia were significant predictors of high BBB permeability in stroke patients. We provide a detailed account of our addition of DP-pCASL and NODDI into the stroke imaging protocol.
563 Post-Approval Three Year Outcomes Study of the Neuroform Atlas Stent for Treatment of Wide-Neck Intracranial Aneurysms
Authors: Jankowitz Brian , Swanson Thomas , Zaidat Osama O. 
Published: March 2023

INTRODUCTION:
Favorable safety and effectiveness outcomes were presented previously for the Neuroform Atlas Stent following the completion of its pre-market study (ATLAS trial [Safety and Effectiveness of the Treatment of Wide Neck, Saccular, Intracranial Aneurysms with the Neuroform Atlas Stent System]) in anterior and posterior cohorts.

METHODS:
The ATLAS post-approval study was a multicenter, prospective, single-arm, open-label study of wide neck (neck ≥ 4mm or dome-to-neck ratio <2) intracranial aneurysms in the anterior and posterior circulations treated with the Neuroform Atlas Stent and approved coils. The primary effectiveness endpoint was complete occlusion (Raymond-Roy class 1) on angiography in the absence of retreatment or significant parent artery stenosis (>50%) through 3 years post-procedure. The primary safety endpoint was occurrence of major stroke, ipsilateral stroke, or neurological death through 3 years post-procedure. Independent adjudication of primary endpoint outcomes was completed by an Imaging Core Laboratory and Clinical Events Committee.

RESULTS:
A total of 146 anterior and 101 posterior cohort subjects from the pre-market study population were enrolled for continued follow-up. Subject demographics and aneurysm anatomy were representative of pivotal trial findings. For anterior subjects, the mean aneurysm size was 6.1±2.4 mm and the mean dome-to-neck ratio was 1.2±0.3 mm. In posterior subjects, the mean aneurysm size was 7±2.7 mm and the mean dome-to-neck ratio was 1.2±0.4 mm. At 3-year follow-up, the percent of target aneurysm progressive occlusion rated the same or better was 84.4% (95% CI, 67.2% - 94.7%) of anterior subjects and 90.0% (95% CI, 73.5% - 97.9%) of posterior subjects. A primary safety event was reported in 0.7% (1/146) of anterior and 1.0% (1/101) of posterior subjects, respectively, with no neurological deaths.

CONCLUSIONS:
The results of the ATLAS post-approval study demonstrate durable treatment effectiveness and favorable safety outcomes.
567 Drivers of 30-day Readmission, Drivers of 30-day Readmission, Reoperation, and Length of Stay Following Clipping Surgery of Unruptured Aneurysms in Elderly: A National Surgical Quality Improvement Program (NSQIP) Study
Authors: Ghaith Abdul Karim , Ghanem Marc , Bendok Bernard R. , Bydon Mohamad 
Published: March 2023

INTRODUCTION:
Elderly population is increasing worldwide with a consistent increase in the incidence of aneurysms. There are limited data evaluating the rate and predictors of reoperation and readmission after microsurgical clipping of unruptured aneurysms in elderly.

METHODS:
Data on elderly patients (≥65 years) who underwent surgical clipping of an unruptured aneurysm between 2016 and 2020 were extracted from the prospective National Surgical Quality Improvement Program registry (NSQIP). Multivariable logistic regression evaluated the independent predictors of nonroutine hospital discharge, length of stay (LOS), 30-day reoperation, and readmission. Shapley additive explanations (SHAP) were calculated for feature importance using the best-performing model.

RESULTS:
A total of 367 elderly patients underwent surgical clipping for both ruptured (N = 142) and unruptured aneurysms (N = 225). Among the 225 unruptured cases, 11.6% (N=26) were readmitted and 6.2% (N = 14) were reoperated after 30 days. The mean LOS is 6.53 days (± 7.15). Most patients were discharged home (N = 160; 71.1%). Morbidity and morbidity probabilities were 2.15% and 3.8%, respectively. Male sex; preoperative BUN; preoperative creatinine and preoperative platelet count (p < 0.05) are more likely to predict 30-day readmission. Male sex, history of cancer , and history of COPD (p < 0.05) are more likely to predict reoperation. LOS was predicted with simple aneurysm , history of sepsis; history of COPD; elective surgery; operative time and days till the operation (p < 0.05). Machine learning using SHAP showed that BUN, platelet count, and sex had the highest impact on readmission; WBC, hematocrit, and sodium levels had the highest impact on reoperation; while operative time and history of sepsis had the highest impact on LOS.

CONCLUSIONS:
Our predictive model validates risk stratification of outcomes of patients undergoing microsurgical clipping of unruptured cerebral aneurysms in the elderly.
749 Medical Student Milestones for Neurosurgery Sub-Interns: A Pilot Study of a Novel Competency-Based Evaluation Tool to Quantitatively Differentiate Residency Applicants
Authors: Bowden Stephen , Tan Hao , Rothbaum Michael , Cook Steven H. , Hanft Simon Jeremy , Heth Jason , Mullin Jeffrey Paul , Orina Josiah N. , Wilson Jonathan Lee , Winer Jesse , Wolfe Stacey Q. , Selden Nathan R. , Chambless Lola Blackwell 
Published: March 2023

INTRODUCTION:
Resident selection is guided by few objective, quantitative datapoints. Utility of a standardized letter of recommendation (SLOR) has been limited by “grade inflation”. The Milestones program in neurosurgery residency standardizes “competence” definitions, recognizes domains of competence beyond patient care and medical knowledge, and highlights deficient areas. A similar approach for neurosurgery sub-interns could provide objective performance data to aid applicant evaluation.

METHODS:
Medical student milestones were adapted from the residency milestones or newly created according to group consensus of relevant competencies. Competency levels were graded ordinally 1 (level of 3rd-year medical student) to 4 (2nd-year resident). Faculty and self-evaluations were completed for 35 sub-interns across eight programs. Evaluators were surveyed on its usefulness. Average and cumulative milestone scores (CMS) within and across programs were evaluated using descriptive statistics. Kendall’s W tested inter-rater agreement. CMS were compared against percentile assignments on LOR using analysis of variance with post-hoc testing.

RESULTS:
The average faculty rating overall was 3.20, similar to that expected of an intern. Students scored highest in coachability and feedback (3.49; 3.67) and lowest in bedside procedural aptitude (2.90; 2.85) in faculty and self-evaluations. Median CMS was 26.5 (IQR 21.75-29.75; range 14-32). CMS in four programs evaluating at least five students ranged at least 11 points. A program with three faculty raters demonstrated scoring agreement across five students (p = 0.024). CMS differed significantly between SLOR percentile assignments, despite 25% of students assigned to top 5%ile while CMS-driven assignment of percentiles significantly differentiated quartiles of students. Faculty and students strongly endorsed the milestones form.

CONCLUSIONS:
The medical student milestones form was well-received and considered useful in objectively differentiating students within and across programs.
771 Levetiracetam Dosing for Seizure Prophylaxis in Neurocritical Care Patients
Authors: Findlay Matt , Hedges Ashley , Menacho Sarah Tamara , Ansari Safdar , Hawryluk Gregory W. J. , Davis Gary , Wolfe Brianne , Lingenfelter Erin 
Published: March 2023

INTRODUCTION:
Levetiracetam has emerged as a safer alternative to phenytoin for seizure prophylaxis in patients presenting with subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI). However, it remains unclear which Levetiracetam dosing regimen is most effective at preventing seizures.

METHODS:
A retrospective cohort study captured adult patients at a quaternary care center presenting with SAH or TBI who received levetiracetam as a total daily dose (TDD) equivalent to or greater than 1000 mg. The primary outcome was the combined seizure incidence, including clinical and subclinical seizures.

RESULTS:
Among the 139 patients identified, 49.6% were male, and the mean age was 53 years. For patients receiving 1000 mg TDD levetiracetam, the administration was 500 mg twice daily. For patients receiving >1000 mg TDD, 77/78 patients received 1000 mg twice daily, and the remaining patient received 750 mg twice daily. A higher seizure incidence was observed, 11.5% vs 1.3%, in patients receiving 1000 mg TDD compared with doses >1000 mg TDD, respectively (p = 0.01), despite no difference in examined confounders, including history of alcoholism (14.8% vs. 19.2%, p = 0.49), benzodiazepine use (65.6% vs. 73.1%, p = 0.28), or propofol use (62.3% vs. 62.8%, p = 0.17). No difference in adverse effects were observed (anemia 1.6% vs. 3.8%, p = 0.44; leukopenia 6.6% vs. 9.0%, p = 0.60; thrombocytopenia 1.6% vs. 1.3%, p = 0.86).

CONCLUSIONS:
Patients may experience a reduced incidence of clinical and electroencephalographic seizures with levetiracetam dosing greater than 1000 mg TDD.
805 External Validation of the McGovern Score for Predicting Pediatric Blunt Cerebrovascular Injury
Authors: Venkataraman Sidish Srinivas , Herbert Joseph , Ravindra Vijay , Bollo Robert John , Cox Charles S. , Gannon Stephen , Limbrick David Delmar , Naftel Robert Partlow , Ugalde Irma , Weiner Howard , Yorkgitis Brian , Shah Manish N. 
Published: March 2023

INTRODUCTION:
Blunt cerebrovascular injury (BCVI) is defined as blunt trauma to the head and neck leading to damage to the vertebral and/or carotid arteries. The risk factors for pediatric BCVI have not been clearly described and which pediatric patients are considered “high-risk” and in need of angiographic/vessel imaging is largely based on clinical and institutional treatment patterns. Our group previously proposed a screening tool, the McGovern score, to identify pediatric trauma patients at high risk for BCVI.

METHODS:
This multicenter, retrospective, hospital-based, cohort study involved data collected for all pediatric (<16 years) trauma patients who presented to the emergency department between 2003 and 2017 at 6 level 1 pediatric trauma centers. This trauma registry was then queried for patients who received a CTA as a screening method for BCVI. Patient age, arrival date, length of follow-up, and MOI were recorded. Glasgow Coma Scale (GCS) on arrival and the presence or absence of a focal neurological deficit. The obtained radiological variables included the presence or absence of a carotid canal fracture, petrous temporal bone fracture, and cerebral infarction as determined on CT scanning. Patients who were found to have BCVI were queried for mode of treatment, type of intracranial injury, artery damaged, and BCVI injury grade. The McGovern score was calculated for all patients who underwent CTA across all data groups.

RESULTS:
1012 patients underwent CTA. 72 of these patients were found to have BCVI, 51 of which were in the external cohort. Across all data groups, the McGovern score has a >80% sensitivity and >98% NPV.

CONCLUSIONS:
The McGovern score is an effective and generalizable screening tool for pediatric BCVI.
865 Survival Benefit of Stereotactic Laser Ablation (SLA) in Newly Diagnosed Glioblastoma Patients: A Matched Cohort Analysis
Authors: Bartek Jiri , Dhawan Sanjay , Chen Clark C C. 
Published: March 2023

INTRODUCTION:
Post-hoc analysis of a previously published matched cohort study suggests improved survival for glioblastoma patients who underwent stereotactic laser ablation (SLA) relative those who underwent a biopsy, particularly for tumors where contrast enhancing (CE) regions were completely covered by thermal ablation.

METHODS:
Thirteen patients with newly diagnosed isocitrate dehydrogenase (IDH) wild type glioblastomas (without H3K27 mutation) who underwent SLA with ablation coverage of >90% of the contrast enhancing region were identified. Control cohort was generated by screening patients who underwent stereotactic biopsy for a newly diagnosed tumor matched for: age (+/- 10 years), location, tumor volume (+/- 30% of CE volume), and methyl-guanine methyl-transferase (MGMT promoter methylation status). Post-operative course, complications, 30-day readmission, and overall survival data were collected.

RESULTS:
The mean KPS for the SLA and biopsy cohorts were comparable (SLA: 90+14; biopsy: 87+16). One patient (8%) in the SLA cohort experienced new-onset diplopia, and one biopsy-only patient (8%) suffered hemi-sensory alteration. There were no 30-day readmissions for either cohort. With a median follow-up of 283 days, the median survival (mOS) for 375 days (∼13 mo) for the SLA treated patient cohort and 264 days (∼ 9 mo) for the biopsy cohort (p = 0.026). To exclude the possibility that this survival difference was due to selection of prognostically favorable patients for SLA, the survival benefit was confirmed by comparison to a second matched biopsy-only glioblastoma cohort from another institution without capacity for SLA. When stratified by MGMT promoter methylation, SLA survival benefit was significant in only patients with methylated tumors (SLA mOS: 620 days (21 mo); biopsy mOS: 171 days (5.7 mo), p = 0.007)

CONCLUSIONS:
For MGMT promoter methylated glioblastomas, SLA treatment was associated with improved survival relative to biopsy-treated patients. Validation of this finding in a prospective study is warranted.
888 Artificial Neural Network Analysis of Evoked Auditory Brainstem Responses for Prediction of Active Auditory Brainstem Implant (ABI) Electrodes in Patients With Neurofibromatosis Type II
Authors: Fatima Nida , Rock Jordan , Galvin John , Peng Kevin , Barnard Zachary , Lekovic Gregory 
Published: March 2023

INTRODUCTION:
Auditory brainstem implantation (ABI) is used to provide auditory sensations through electric stimulation of the cochlear nucleus and is a key strategy for hearing rehabilitation in patients with neurofibromatosis type II (NF2). The exact position of the 3 by 7 electrode array with respect to the cochlear nucleus is not known, due to complex anatomy following tumor removal, procedures during surgery, potential distortions to the anatomy, and post-operative array migration, and other factors.

METHODS:
A retrospective study of a prospectively maintained database of ABI users with evoked brainstem responses was carried out at an academic institution. Multi-class classification was conducted using the multilayer perceptron (MLP) feed forward neural network model (FF-NN) to classify and predict the post-operative active electrodes.

RESULTS:
1,177 electrodes were stimulated intraoperatively among 85 patients [females, n = 48 (56.6%)]. ABI was implanted to the right and left side in 44 patients (51.7%) and 43 patients (48.3%) respectively. The mean follow-up of ABI was 29.6 months (range, 18-33.4 months). Notably, the heat map showed that electrodes at the center and the medial end (E9-16) of the array showed higher likelihoods of being active, irrespective of right or left side. The network was trained for 500 epochs with a learning rate of 0.3 and achieved a mean classification of about 92.3%. The open accessible software for predicting the monopolar electrode stimulation postoperatively based on bipolar intraoperative stimulation can be found here at: https://hifla.org/abi

CONCLUSIONS:
An ideal MLP FF-NN structure was achieved and hence may result in understanding more precisely about the ABI stimulation and bringing consistency among the neurosurgeons and audiologists worldwide.
Softball Pitchers’ Body Segment Girths Are Associated with Varied Biomechanics at Ball Release of the Pitch
Authors: FRIESEN KENZIE B. , OLIVER GRETCHEN D. 
Published: March 2023

ABSTRACT

Purpose
The purpose of this study was to examine the relationships between pitcher trunk and throwing arm girth with kinematics at ball release of the softball pitch. Softball pitchers can be of various shapes and sizes; however, it is unknown if segment girth might influence pitch biomechanics. Because of the importance of body positioning at ball release of the windmill pitch, this study examined the relationship between segment girth and pitch biomechanics at ball release.

Methods
Forty-two pitchers volunteered to participate (1.706 ± 0.061 m, 74.98 ± 15.94 kg, 15.5 ± 1.7 yr). Participants’ throwing upper arm, chest, waist, and hip girth were measured. Participants then pitched fastballs to a catcher (43 ft) while an electromagnetic motion capture system synced with a force plate and motion analysis software collected kinematic data (sampled at 240 Hz).

Results
Linear regressions revealed that upper arm, chest, and waist girth were associated with throwing arm shoulder horizontal abduction. Greater segment girth was associated with less horizontal abduction at ball release of the pitch.

Conclusions
Segment girth is related to pitch biomechanics and may influence body positions at crucial softball pitch events such as ball release.

Clinical Relevance
Understanding biomechanical differences according to body segment girth is important for safe and optimal player development and performance.
The West Africa Lassa fever Consortium pre-positioned protocol for a Phase II/III adaptive, randomised, controlled, platform trial to evaluate multiple Lassa fever therapeutics
Authors: Bourner Josephine , Salam Alex Paddy , Jaspard Marie , Olayinka Adebola , Fritzell Camille , Goncalves Bronner , Vaillant Michel , Edwards Tansy , Erameh Cyril , Ajayi Nnennaya , Ramharter Michael , Olliaro Piero ,   The WALC Work Package 2 Working Group
Published: March 2023

Background: This is a standardized, pre-positioned protocol for the coordinated evaluation of Lassa fever therapeutics. The protocol is the product of discussions that took place in 2021 and 2022 among international investigators from a wide range of scientific and medical disciplines working together within the West Africa Lassa fever Consortium (WALC). Methods: This is a clinical Phase II/III multicentre randomised controlled platform trial using a superiority framework with an equal allocation ratio and a composite primary endpoint of all-cause mortality OR new onset of i) acute kidney failure (AKF), OR ii) acute respiratory failure (ARF), OR iii) shock assessed from enrolment (D0) to D28. Discussion: This pre-positioned protocol was developed by the WALC and made available for adaptation and implementation by the wider Lassa fever research community in order to generate efficient, reliable, and comparable evidence for Lassa fever therapeutics.