bluuebunny/crossref_metadata_2025_split huggingface dataset:
195 3D Genome Structure and Epigenetic Transcription Regulation in Pediatric High-Grade Glioma
Authors: Saratsis Amanda M. , Huang Tina , Wang Juan , Hu Ye , Piunti Andrea , Bartom Elizabeth , Shilatifard Ali , Yue Feng 
Published: March 2022

INTRODUCTION:
Pediatric high-grade gliomas (pHGGs), including glioblastoma multiforme (GBM) and diffuse intrinsic pontine glioma (DIPG), are highly morbid brain tumors. Up to 80% of DIPGs harbor a somatic missense mutation in genes encoding Histone H3. To investigate whether the H3K27M mutant protein is associated with distinct chromatin structure affecting transcription regulation, we generated the first high-resolution Hi-C and ATAC-Seq maps of pHGG cell lines, and integrated these with tissue and cell genomic data.

METHODS:
We sequenced patient-derived cell lines (DIPG n = 6, GBM n = 3, normal n = 2) and frozen tissue specimens (DIPG n = 1, normal brainstem n = 1). Analyses included cell line RNA-Seq, ChIP-Seq (H3K27ac, H3K27me3, H3K27M) and genome-wide chromatin conformation capture (Hi-C), as well as tissue ATAC-Seq. Publicly available pediatric glioma tissue ChIP-Seq data was integrated with cell data.

RESULTS:
We identified tumor-specific enhancers and regulatory networks for known oncogenes in DIPG and GBM. In DIPG, FOX, SOX, and STAT families were among top H3K27Ac enriched motifs. Significant differences in Topologically Associating Domains (TADs) and DNA looping were observed at OLIG2 and MYCN in H3K27M mutant DIPG, relative to wild-type GBM and normal cells. Pharmacologic treatment targeting H3K27Ac (BET and Bromodomain inhibition) altered these 3D structures. Functional analysis of differentially enriched enhancers in DIPG implicated SOX2, SUZ12, and TRIM24 as top activated upstream regulators. Distinct genomic structural variations leading to enhancer hijacking and gene co-amplification were identified at A2M, JAG2, and FLRT1.

CONCLUSION:
We show genome structural variations enhancer-promoter interactions that impact gene expression in pHGG in the presence and absence of the H3K27M mutation. Our results imply that tridimensional genome alterations may play a critical role in the pHGG epigenetic landscape and thereby contribute to pediatric gliomagenesis. Further studies examining the impact of the alterations are therefore underway.
301 1000 Cases of Surgically Treated Aneurysmal Subarachnoid Haemorrhage: Changes in Practice and Clinical Outcomes
Authors: Budohoski Karol P. , Tajsic Tamara , Bal Jarnail , Levrini Virginia , Guilfoyle Mathew , Helmy Adel , Kirkpatrick Peter , Kirollos Ramez , Trivedi Rikin 
Published: March 2022

INTRODUCTION:
Aneurysmal subarachnoid haemorrhage (aSAH) remains a complex and multidisciplinary pathology. With endovascular methods expanding fewer patients are treated surgically.

METHODS:
All patients following surgery for aSAH between 2007 - 2019 were included. Baseline characteristics outcomes were analysed. We compared outcomes between experienced (=50 independent cases) and non-experienced surgeons (<50 independent cases), and high-volume (=20 cases/year) and low-volume surgeons (<20 cases/year).

RESULTS:
970 patients with 1003 aneurysms were identified with median age 56. 73.8% were WFNS grade 1 or 2. The majority of aneurysm were on the middle cerebral artery (41.4%), anterior communicating artery (27.6%) and posterior communicating artery (17.5%). 37.4% of aneurysm were <7 mm in size. Technical error rate was 6%, resulting in a post-operative infarct in 4.9% of patients. 19 patients (2%) died within 30 days of admission. There were no significant changes in technical error rates or post-operative infarcts or death (p = 0.79 and p = 0.77 respectively) over the study period. There was no difference in post-operative infarctions between experienced and non-experienced surgeons (p = 0.28), but there was a difference when comparing high-volume vs. low-volume surgeons (p = 028).

CONCLUSION:
We present real world data on surgical indications and outcomes after aSAH. We believe that this constitutes important data demonstrating good retention of skills and good clinical outcomes in a very dynamic field of cerebrovascular surgery. We also demonstrate a relationship between surgical case volume and outcomes.
305 Characterizing and Comparing Brain Injury Associated With Traditional Self-Retracting Brain Retractors With Novel Tubular Retractors
Authors: Naeem Abdul , Dryden Georgia , Hammond Robert , Speechley Mark , Wade Kevin A. , Boulton Melfort R. 
Published: March 2022

INTRODUCTION:
Tubular retractors are FDA approved and in the Neurosurgical marketplace, but adaptation has been hampered by lack of evidence showing superiority over traditional retractors when performing subcortical surgery.

METHODS:
Nine porcine models underwent a simulated neurosurgical operation. Retractors were inserted for four hours after which the porcine model was euthanized. The en-bloc extracted porcine brain was fixed in 10% formalin, paraffin embedded, sectioned at 4 um and stained with hematoxylin and eosin (H&E) using standard laboratory protocols. Computer algorithms were generated to calculate areas of cerebral edema and hemorrhage adjacent to retractor surfaces.

RESULTS:
Using a two-tailed t-test with a significance level of 0.05, traditional brain retractors were associated with statistically significantly greater cerebral edema when compared to tubular retractors (17.36 um2 vs. 12.42 um2; p = 0.0038). There was no statistically significant difference in mean areas of hemorrhage between traditional brain retractors and tubular retractors noted (3.43 um2 vs 3.60 um2; p = 0.8297).

CONCLUSION:
Tubular retractors are associated with significantly less edema in surrounding brain than traditional retractors. On histopathological merits, this study supports the application of tubular retractors over traditional retractors.
314 Spinal Versus General Anesthesia for Lumbar Spine Surgery: Prospective Analysis of Quality of Life, Postoperative Fatigue and Cognitive Dysfunction
Authors: De Biase Gaetano , Gruenbaum Shaun , Quinones-Hinojosa Alfredo , Abode-Iyamah Kingsley 
Published: March 2022

INTRODUCTION:
Low back pain is the leading cause of years lost to disability worldwide, and this burden is increasing as our population ages. Postoperative fatigue and postoperative cognitive dysfunction (POCD) commonly affect patients during their recovery period and diminish their quality of life. There has recently been increasing interest in the use of spinal anesthesia (SA) for lumbar spine surgery. To date the literature that has compared spine surgery under SA versus general anesthesia (GA) has been focused exclusively on safety, perioperative outcomes and costs.

METHODS:
We conducted a prospective non-randomized study in patients undergoing elective lumbar spine surgery under SA or GA by a single surgeon. Fatigue was assessed with a fatigue VAS scale (0-10) and with Chalder Fatigue Scale (CFQ); quality of life with the Medical Outcomes Study 12-item Short Form (SF-12); differences in cognition with the Mini-Mental State Exam(MMSE). Patients were assessed before the surgery to acquire their baseline and again 1 month after surgery.

RESULTS:
Fifty patients completed the study, 25 underwent surgery under spinal and 25 under general anesthesia. The groups were homogeneous for baseline clinical characteristics; with no differences in preoperative baseline fatigue, quality of life and cognition, and physical and mental components of the SF-12 between the SA and GA groups. At 1-month after surgery spinal anesthesia when compared to general anesthesia had better fatigue scores: i) fatigue VAS (2.9 ± 1.5 versus 5.6 ± 2.3, (p < 0.0001)); ii) fatigue CFQ (11.2 ± 3.1 versus 16.5 ± 3.9 (p < 0.0001)). At 1-month after surgery we observed a significant difference in the physical component of SF-12, spinal anesthesia having 38.8 ± 8.9 versus 29.4 ± 10.3 (p = 0.002). We did not observe significant postoperative differences in mental component of SF-12. There was no significant difference in MMSE at 1-month follow-up.

CONCLUSION:
At 1 month postop patients that underwent surgery under spinal anesthesia had less postoperative fatigue and better quality of life.
317 Comparison of One-Day Combined Versus Staged Anterior and Posterior Cervical Decompression, Fixation and Fusion
Authors: Mozaffari Khashayar , Chalif Eric , Stellon Michael A. , Patrick Hayes , Sparks Andrew , Almeida Neil , Rosner Michael K. 
Published: March 2022

INTRODUCTION:
Current management of cervical stenosis at times can involve both anterior and posterior decompression, stabilization and fusion. Although these procedures can be done in a combined or staged fashion, there is a scarcity of literature on this topic.

METHODS:
A retrospective cohort analysis was conducted on consecutive patients at a single institution between July 2015 and April 2019 who underwent either single day combined or separate day staged surgeries. Demographics, comorbidities, length of stay, perioperative complications, and inpatient medication use were compared between cohorts. Multivariable analysis was used to adjust for differences in demographics and other confounding covariates.

RESULTS:
80 patients were analyzed (combined = 58, staged = 22). Comparing combined versus staged, there were no differences in baseline demographics. The administration of morphine equivalents was similar comparing combined and staged (569 vs 681 morphine equivalents, P = 0.66). Staged patients had significantly longer time in the operating room (7.2 vs 8.5 hours, P < 0.01) and longer duration of general anesthesia (6.7 vs 7.6 hours, P < 0.01). Incidence of post-operation delirium was significantly higher in the staged group (13.2% vs 50.0%), with an adjusted odds ratio of 23.3 (95% CI: 2.6 – 212.1; P < 0.01). Dysphagia was the most common post-operative complication seen in 43 patients (53.7%). Patients age > 60 had total length of stay 39.1% ± 15.0% longer than those age = 60 (multivariable adjusted mean ± standard error; P = 0.02).

CONCLUSION:
Staging anterior and posterior cervical decompression, stabilization and fusion is associated with longer usage of the operating room, longer duration of general anesthesia, and increased incidence of perioperative complications.
319 Multi-level Stabilization Screws Prevent Proximal Junctional Failure and Kyphosis in Adult Spinal Deformity Surgery: A Comparative Cohort Study
Authors: Kaufmann Ascher , Claus Chad F. , Houseman Clifford M. , Tong Doris , Carr Daniel A. , Soo Teck M. 
Published: March 2022

INTRODUCTION:
Proximal Junctional Kyphosis (PJK) and Failure (PJF) occurred in up to 40% of adult spinal deformity (ASD) patients who underwent open thoracolumbar fusion. Proximal stabilization techniques were studied to prevent PJK/PJF without conclusive results.

METHODS:
This is an observational longitudinal cohort study comparing MLSS with standard stabilization instrumentation. We reviewed the charts of consecutive ASD patients who underwent open thoraco-lumbar (TL) fusion (>3 levels, extending cranially above T6 and caudally below L1) from 2009-2017 and were followed for >2 years postoperatively. We defined PJF using International Spine Study Group (ISSG) criteria and PJK as a Cobb angle increase >10o. We defined the upper-instrumented-vertebra (UIV) as the most cephalad vertebral body with bilateral MLSS. Confounders, MLSS-specific complications, radiographic outcomes were collected. We evaluated comparability between groups using univariate analyses. We adjusted for covariates by using multivariable regressions modeling PJF and PJK separately with a p-value <.008 considered significant after Bonferroni correction. We used sensitivity analysis to account for those lost to follow-up.

RESULTS:
Seventy-six patients (50 MLSS vs 26 controls) were included. MLSS patients were significantly older (64.5 ± 8.9 vs. 54.8 ± 19.9 years, p = .024). MLSS patients had significantly lower PJF incidence (10.0% vs. 30.8%, p = .023) and less kyphosis (1.3o ± 5.3o vs. 5.2o ± 6.3o, p = .014). MLSS was independently associated with decreased kyphosis compared to controls (B: -4.5, 95% CI: -7.72 – -1.29, p = .007). MLSS-specific complications were not significantly different between the cohorts.

CONCLUSION:
MLSS is safe and efficacious in reducing PJF/PJK in ASD patients undergoing open, long-construct TL fusion.
320 The Effects of the COVID-19 Pandemic on Penetrating Neurotrauma at a Level 1 Trauma Center
Authors: Yang George L. , Johnson Mark D. , Solomon Daniel , Ferguson Andrew , Wright James Monroe , Johnson Reid A. , Gerges Christina , Parr Ann M. , Ngwenya Laura B. 
Published: March 2022

INTRODUCTION:
The COVID-19 pandemic forced the implementation of social distancing guidelines to minimize spread of the coronavirus. However, it is not yet understood what effects these precautions had on the rates of penetrating neurotrauma.

METHODS:
We retrospectively analyzed neurotrauma data from our institutional trauma registry from distinct periods defined as pre-COVID-19 (March 2019-September 2019) and COVID-19 (March 2020-September 2020). Demographics, injury characteristics, mechanisms of trauma, and past medical history (including psychiatric diagnosis) were collected. Data were analyzed for between-group differences and presented as odds ratios.

RESULTS:
We observed a significant rise in the number of neurotrauma cases in 2020 (558 vs. 630, OR 1.129 [1.0071, 1.2657]). There was a decrease in the proportion of male victims (71.3% vs. 68.6%, p = 0.03). There were significant differences noted in the mechanism of injury between groups. Patients in 2020 were less likely to present with falls (42.3% vs. 34.3%, OR 0.7119 [0.5627, 0.9005]) and more likely to present with GSW (4.48% vs. 7.78%, OR 1.7981 [1.0951, 2.9523]). Of the patients with penetrating cranial injuries, the most common motive was assault (56.7% vs. 60.0%), followed by self-inflicted (13.3% vs. 20.0%) and accidental (20.0% vs. 18.3%) with a significant difference between years (p = 0.0043). The presence of comorbid psychiatric illness or substance abuse did not confer an increased odds of presenting with penetrating injuries. No significant differences were noted in mean arrival or discharge GCS or injury severity as measured by ISS. However we did observe significant increases in patients presenting with bilaterally reactive pupils (48.3% vs 59.3%, p = 0.0025), patients discharged home (27.6% vs 37.3%, p = 0.0002), and survival at 6 months (41.4% vs. 54.2%, p = 0.0188).

CONCLUSION:
We observed a higher rate of penetrating neurotrauma while social distancing measures were in place. It is unclear if the psychosocial effects of quarantine and social distancing had a causative relationship with the increased rates of assault and self-inflicted penetrating injuries.
323 Prevalence and Predictors of Inappropriate Pre-injury Antithrombotic Use in Patients Presenting with TBI
Authors: Mashouf Leila A. , Nieves Amber , Matos Jason , Yaffe Michael , Stippler Martina 
Published: March 2022

INTRODUCTION:
A growing proportion of the US population is on antithrombotic therapy (AT), expanding most significantly within the elderly subpopulation. The intended benefits of AT are balanced by known increased bleeding risk, salient after traumatic brain injury (TBI). Inappropriate pre-injury AT (IAT) in patients presenting with TBI confers unbalanced risk of poor outcomes and has yet to be described in existing literature.

METHODS:
A retrospective chart review was performed on all patients with TBI and pre-injury AT who presented to our institution between January 2016 and September 2020. Demographic and clinical data was collected from the medical record. IAT status was determined through established clinical algorithms in combination with American College of Cardiology practice guidelines. Clinical predictors were determined by logistic regression.

RESULTS:
Of 169 included patients, 59% were male (n = 100) and mean age was 82 years. AT agents included aspirin (n = 46), clopidogrel (n = 45), coumadin (n = 77), dabigatran (n = 4), rivaroxaban (n = 17), and apixaban (n = 30). Overall surgical intervention, complication, and death rates were 7.7%, 15.4%, and 20.1%, respectively. IAT was found in 10.6% of patients overall: in 41% (n = 6) of patients with documented indication of pulmonary embolism, in 6.2% with documented indication of atrial fibrillation (AF) (n = 6), in 24% with documented indication of cardiac stents (n = 5). Age was a significant negative predictor of IAT use in patients with documented indication of AF (p=0.009). Gender, race, and AT agent were not significant predictors.

CONCLUSION:
1 in 10 patients presenting with TBI were found to be on IAT. Our study is the first to describe this population and warrants investigation into workflow interventions that initiate verification or deprescription of AT by neurosurgeons treating TBI and outpatient prescribers.
327 Prophylactic Antibiotics Do Not Prevent CNS Infection in Civilian Gunshot Wounds to the Head
Authors: Gilbert Olivia , Podet Adam , Hayden Ellery , Wilson John , Crutcher Clifford , Tender Gabriel C. 
Published: March 2022

INTRODUCTION:
Civilian gunshot wounds to the head (GSWH) are an ongoing epidemic in the US, with incidence rising each year. They are frequently devastating, with case fatality rates approaching 91%, accounting for fatalities occurring in the hospital and at the scene of injury. Although military GSWH are robust, data and management guidelines for civilian GSWH is relatively lacking. Specifically, the administration of prophylactic antibiotics in GSWH patients remains controversial. Prior studies indicate the incidence of intracranial infection after civilian GSWH to be as high as 25%, with significant impact on morbidity and mortality.

METHODS:
We retrospectively reviewed survivable GSWH at our level 1 trauma center between 2012-2017. Patients were assessed for CNS infection, and categorized with regard to the use of prophylactic antibiotics, length of stay, GCS at presentation, bullet trajectory, and demographics.

RESULTS:
236 patients sustained survivable GSWH. 12/236 (5.1%) patients developed CNS infection following GSWH, and 3/12 (25%) of those patients had not received prophylactic antibiotics. Of the 133 patients who received prophylactic antibiotics, 10 (7.5%) subsequently developed CNS infection. Infection was diagnosed more commonly in patients who received antibiotics, but this was not statistically significant (p = 0.138). Bullet trajectories through the paranasal sinuses or oropharynx were significantly more likely to result in CNS infection (OR 3.04, p = 0.0624). Patients who underwent decompressive surgery and patients who underwent invasive ICP monitoring had significantly higher odds of developing CNS infections (OR 17.7, p = 0.00616; OR = 0.24, p = 0.048).

CONCLUSION:
Decompressive surgery, invasive ICP monitoring, and bullet trajectory were statistically significant factors associated with development of CNS infection following GSWH. Prophylactic antibiotics did not reduce the incidence of CNS infection, and may have increased the risk of infection.
332 Speech Dysfunction in Deep Brain Stimulation Patients
Authors: Chandra Vyshak , Wong Joshua , Hegland Karen , Herndon Nicole , Foote Kelly D. 
Published: March 2022

INTRODUCTION:
Deep brain stimulation (DBS) is a neuromodulatory therapy that is predictably effective for treatment of Parkinson’s disease (PD). The precise effect of DBS on speech function is variable, however, and patients with more impaired speech function prior to surgery are thought to be at increased risk of worsening speech function post surgically.

METHODS:
Patients with a diagnosis of Parkinson's disease who are at least 40 years old (at first DBS surgery) that have had speech assessments as part of normal clinical care 12 or fewer months prior to DBS surgery (pre-DBS) and within 12 months after surgery completion (post-DBS) were included in the study - 130 total patients. Preoperative and postoperative speech testing data was compiled, along with DBS programming settings including lead type (directional or conventional), pulse width, frequency, amplitude, active contacts, and battery type at time of speech evaluations (estimated to be 6- and 12-months post DBS surgery).

RESULTS:
A mixed effect linear model with lognormal errors to analyze the speech pathology severity scores. Site (STN, GPi), and hemisphere involvement (Unilateral, Bilateral) were modeled as completely crossed between-patient fixed effects. Speech severity, respiratory severity, and laryngeal severity were found to be significantly worsened post-operatively in patients that obtained GPi DBS, contrary to our original hypothesis. Orofacial severity worsened post-operatively in patients that obtained STN DBS.

CONCLUSION:
GPI DBS patients had several categories of statistically significant worsening of speech, contrary to our hypothesis. A future study based on target alone will not be useful, but preliminary data studying specific neuroanatomic localization of stimulation and activation of fibers should prove more fruitful.
338 Disparate Use of Deep Brain Stimulation for Parkinson’s Disease in Black Patients is Driven by Barriers to Access that Arise Before Surgical Referral
Authors: Skelton Henry M. , Grogan Dayton , Laxpati Nealen , Miocinovic Svjetlana , Gross Robert E. , Yong Nicholas A. 
Published: March 2022

INTRODUCTION:
Deep brain stimulation (DBS) is an effective therapy for Parkinson’s disease (PD) that can provide substantial improvements in quality of life for patients inadequately controlled with medication. However, there is severe racial disparity in its use, with Black PD patients being much less likely to be treated with DBS than White patients. We hypothesized that the extensive process of patient selection and workup limits access to DBS, and we analyzed the records of a major movement disorder and DBS center to determine if this barrier to access was apparent.

METHODS:
We reviewed a database that includes every patient considered for DBS between 2016 and February of 2021. We cross-tabulated the patients by race, as documented in the medical record, and progression to surgical intervention. We determined whether there was a significant difference in the proportion of patients who were not treated with DBS via Fisher’s exact test.

RESULTS:
Out of 211 PD patients evaluated by a DBS movement specialist and referred for preoperative workup since 2016, 10 (5%) were indicated to be Black, compared to 160 (76%) White, 7 (3%) Asian, and 34 (16%) Unknown. Of those, 7/10 (70%) Black patients were treated with surgery, compared to 123/160 (77%) White, 5/7 (71%) Asian, and 23/34 (68%) Unknown (p = 0.61, Fisher’s Exact Test).

CONCLUSION:
While very few Black patients were referred to DBS Clinic, there was no significant difference between racial groups in the likelihood of receiving surgery once referred. This suggests that the disparity arises before preoperative workup, with potential candidates for treatment never reaching DBS clinic. Future work should attempt to identify factors driving this disparity, with particular attention paid to referral patterns. Notably, these results do not exclude the possibility that the general burden of preoperative evaluation and postoperative management might influence decisions on whether to refer patients.