bluuebunny/crossref_metadata_2025_split huggingface dataset:
146 Human Interictal Epileptiform Discharges are Traveling Waves Reflecting Ictal Self-organization
Authors: Smith Elliot , Liou Jyun-you , Merricks Edward , Davis Tyler , Thomson Kyle , Greger Bradley , House Paul A. , Emerson Ronald , Goodman Robert R. , McKhann Guy M. , Schevon Catherine , Rolston John D. 
Published: March 2022

INTRODUCTION:
Interictal epileptiform discharges (IEDs), are large intermittent electrophysiological events observed between seizures in epileptic patients. While seizures are infrequent and unpredictable, IEDs are far more common, occurring several times per minute (0.67 IEDs per minute in this dataset). The relative frequency of IEDs makes them an alluring indicator of epileptogenic brain, especially when compared to more scarce and unpredictable seizures. Yet despite the relative abundance of IEDs, it remains unknown how they relate to seizures.

METHODS:
To better understand this relationship, we examined semi-chronic, multi-day recordings of 96-channel microelectrode arrays implanted in human epilepsy patients. These recordings—spanning single cell action potentials to local field potentials—allowed us to study the microscale spatiotemporal organization of over 45,000 IEDs across 10 patients. We used ordinary multivariate linear regression to estimiate IED speed and direction, and vonMises Mixture models to cluster bimodal IED directions in to sub-distributions.

RESULTS:
These recordings showed that the majority (66.4%) of IEDs propagate across neocortex as traveling waves with a dominant direction (Hermans-Rasson Tests, all p < 10-3). IED traveling wave direction distributions were bimodal in 8 of the 10 subjects, with a median difference between sub-distributions of 178 degrees. Firing rates and voltages of IEDs in each sub distribution were not significantly different, however, the proportion of IEDs in each sub-distrbution and their speeds and directions were different among sub-distributions, and mimicked sub-distributions of ictal discharges.

CONCLUSION:
These results show that IEDs propagate across the surface of the brain as traveling waves, and the that their directions mimic those of discharges occuring during seizures. Furthermore, these results provide a new understanding of epileptic brian tissue, and suggest that spatial features of IEDs may be used to help diagnose and treat medically refractory epilepsy.
147 Cranial Nerve Metastasis Treated with Stereotactic Radiosurgery: A Single Institution Experience
Authors: Shahsavari Nastaran , Ahmad Maleeha , Ding Victoria , Pollom Erqi , Han Summer , Soltys Scott G. , Chang Steven D. , Meola Antonio 
Published: March 2022

INTRODUCTION:
Cranial nerves are rarely affected in patients with solid, extra-axial malignant tumors. Involvement of the cranial nerves can severely impact the patient’s symptoms and quality of life. Cancer invasion of cranial nerves typically occurs either as leptomeningeal disease (LMD) by CSF spread or as direct spread (DS) from the primary and metastatic head and neck tumors.

METHODS:
All patients with cranial nerve metastases treated with SRS at our institution between April 2003 and February 2021 were retrospectively identified from electronic health records. Clinical assessment and magnetic resonance imaging (MRI) were performed pre-SRS, and 1 to 3 months post-SRS. Kaplan-Meier estimator was used for evaluating overall and progression-free survival (OS and PFS) at 6 months and the log-rank test was applied to compare survival by each disease subgroup.

RESULTS:
Our study cohort consisted of 17 patients including 8 LMD and 9 DS patients. The median age was 60.9 years at initial SRS. In total, 30 cranial nerve metastases were treated with SRS. The median duration of follow-up was 17 months. Among 13 pre-SRS symptomatic patients, symptoms improved in 5 patients (38.4%), remained unchanged in 7 patients (53.8%), and worsened in one patient (7.6%). Local tumor control was achieved in 12 patients (70.6%). Three patients died within 6 months of the initial SRS date, all of whom belonged to the LMD group. Overall survival at 6 months was 82.4% for the entire cohort, with 62.5% and 100% for the LMD and DS subgroups, respectively (P = 0.048). There was insufficient evidence to suggest a difference in progression-free survival between subgroups (p = 0.198).

CONCLUSION:
Our study shows that SRS may be an effective treatment for cranial nerve metastasis providing 70.6% local tumor control, and clinical stability or improvement in over 92% of symptomatic cases.
152 Intraoperative Detection of IDH Mutation Status and Residual Tumor in Glioma
Authors: Garcia Diogo P. , Brown Hannah , Chen Rong , Jentoft Mark E. , Middlebrooks Erik , Chaichana Kaisorn L. , Quinones-Hinojosa Alfredo , Cooks Graham 
Published: March 2022

INTRODUCTION:
Maximizing surgical resection in gliomas is associated with a survival benefit, which can be negated by surgery-inflicted neurological deficits, making it imperative to achieve extensive resection without compromising non-infiltrated tissue. Current technologies are sub-optimal in providing intra-operative molecular characterization.

METHODS:
This is a prospective cohort study using intraoperative DESI-MS analysis of smears produced from freshly obtained brain tumor biopsy samples under neuro-navigation guidance to evaluate IDH mutation status via 2-hydroxyglutarate (2-HG) intensity and TCP via measurement of N-acetylaspartic acid (NAA) intensity and characteristic lipid profiles. Blinded review of the smears by a senior neuropathologist was used for validation of IDH mutation status and TCP estimates.

RESULTS:
A total of 465 tumor biopsies from 77 enrolled patients have been collected and analyzed. Evaluation of TCP in an optimization stage based on NAA intensity in 203 biopsies yielded sensitivity, specificity, and accuracy values of 91, 76, and 83%, while assessment through lipid profiling yielded 76, 85, and 81%, respectively. Assessment of IDH mutation status from 71 core biopsies resulted in sensitivity, specificity, and accuracy values of 89, 100 and 94%, respectively. Further optimization of IDH assessment by measurement of the relative intensity of 2-HG against its endogenous standard, glutamate, in nine patients yielded 100% sensitivity, specificity, and accuracy.

CONCLUSION:
We present preliminary results from the first and largest study using DESI-MS to intraoperatively evaluate TCP and IDH mutation status in gliomas. Prospectively, we propose a further modification to allow estimation of TCP and IDH mutation status in surgical cavities without the need of a biopsy by placing a surgical material (e.g. cottonoid) along the surgical margin and transferring material from the blot to a microscope slide prior to DESI-MS analysis.
154 Pituitary Adenomas Evade Apoptosis via Noxa Degradation in Cushing’s Disease
Authors: Asuzu David , Alvarez Reinier , Mandal Debjani , Chittiboina Prashant 
Published: March 2022

INTRODUCTION:
Cushing’s disease (CD) arising from ACTH-secreting pituitary adenomas is associated with severe morbidity and mortality. Pathogenic mechanisms of sporadic CD are poorly understood. Using novel syngeneic, pairwise transcriptomic analysis of surgical tissues, we identified transcriptional upregulation of PMAIP1 (encoding pro-apoptotic noxa) in CD adenomas compared to adjacent normal gland.

METHODS:
We investigated noxa protein levels by immunohistochemistry in 10 CD adenoma/normal pairs and by Western blotting in two syngeneic pairs of primary human cell lines from CD adenomas. We validated our key findings in ATT20 murine pituitary corticotroph tumor cells and in corticotroph-enriched murine cell lines mCortEFGF. Proteasomal-mediated degradation was assessed by cycloheximide chase assay. Bortezomib was used for proteasomal inhibition. Cell viability was assessed using CellTiterGlo (Promega).

RESULTS:
Despite PMAIP1 mRNA overexpression in CD, we found consistently low noxa protein in CD adenomas compared to surrounding normal glands but not in growth hormone secreting adenomas or prolactinomas. A cycloheximide assay demonstrated proteasomal-mediated noxa degradation mCortEFGF cells, which was rescued by proteasomal inhibition using bortezomib. Bortezomib treatment decreased cell viability and induced apoptosis in mCortEFGF cells, and also inhibited growth with apoptosis induction in CD adenoma primary cells.

CONCLUSION:
We identified proteasomal-mediated noxa degradation as a mechanism of escape from apoptosis in CD adenomas despite PMAIP1 transcriptional upregulation. Proteasomal inhibition using bortezomib rescued noxa protein levels and induced apoptosis in a dose-dependent fashion. Bortezomib, an FDA approved medication for mantle cell lymphoma, may represent a novel therapeutic target for patients with CD.
157 Supramarginal Resection Impact on Overall Survival for IDH-Wildtype Glioblastoma According to Their Cell Density Distribution and Infiltration Profile: A Mathematical Model
Authors: Vivas-Buitrago Tito , Domingo Ricardo , Tripathi Shashwat , De Biase Gaetano , Ramos-Fresnedo; Desmond A. Brown Andres , Akinduro Oluwaseun , Sherman Wendy , Sabsevitz David S. , Bendok Bernard R. , Parney Ian F. , Chaichana Kaisorn L. , Swanson Kristin R. , Quinones-Hinojosa Alfredo 
Published: March 2022

INTRODUCTION:
Supramarginal resection of the T2-FLAIR beyond the T1 contrast enhancement has been suggested to further improve overall survival in glioblastoma (GBM) patients, with a potentially enhanced role in IDH-wildtype. GBMs present with high variability in tumor cell density, distribution, and infiltration patterns evidenced in imaging and histological analysis. Preoperative estimation of GBM grow kinetics with advanced mathematical models can provide further insight for surgical planning.

METHODS:
Volumetric measurements from T1 contrast-enhancing (CE) and T2-FLAIR regions of interest from retrospective pre and postoperative MRIs of patients that underwent a gross total resection of the CE were obtained. Tumor invasiveness profile (proliferation/diffusion (ρ/D) ratio) was calculated using the following formula: where VFL and VT1 are the preoperative FLAIR and contrast-enhancing volumes, respectively. Patients were then split into nodular (ND), moderately diffuse (MD), and highly diffuse (HD) subgroups based on their tumor invasiveness profile. SMR extension and survival analyses were performed among groups.

RESULTS:
101 patients met the criteria for this study. Tumors were classified as ND (n = 34), MD (n = 34), and HD (n = 33) tumors. On multivariate analysis, increasing SMR had a significant positive correlation with OS only in MD and HD tumors (HR 0.98; 95% CI, 0.98–0.99; p = 0.05, and HR 0.98; 95% CI, 0.97–0.99; p = 0.02), respectively. On threshold analysis, OS benefit was seen with SMR from 10% to 29%, 10%-59%, and 30%-90%, for ND, MD, and HD, respectively.

CONCLUSION:
SMR impact on overall survival in this cohort of IDH-wildtype is significantly influenced by the degree of tumor invasiveness. The results of this study showed increased overall survival with increasing SMR for moderate and highly invasive tumors. Further analysis with SMR grouped in 10% intervals demonstrated an increase in overall survival for all groups, with a lower SMR extension to benefit nodular tumors.
158 Comparison of Cost and Complication Rates for Profiling Hospital Performance in Lumbar Fusion for Spondylolisthesis
Authors: Greenberg Jacob K. , Olsen Margaret , Dibble Christopher , Zhang Justin , Pennicooke Brenton Henry , Yamaguchi Ken , Kelly Michael , Hall Bruce , Ray Zack 
Published: March 2022

INTRODUCTION:
Despite growing interest among payers in profiling both the cost and safety of common surgeries, such as lumbar fusion, there is sparse evidence describing the statistical reliability of such measures when applied to lumbar fusion for spondylolisthesis.

METHODS:
We used State Inpatient Databases from nine states to study patients undergoing lumbar fusion for spondylolisthesis from 2010-2017. The study outcome was the statistical reliability of three distinct quality/value metrics. Statistical reliability was measured as the amount of variation between hospitals relative to the total amount of variation for each measure. Total variation includes both between-hospital variation (“signal”) and within-hospital variation (“statistical noise”). Thus, reliability equals signal over (signal plus noise) and ranges from 0-1. We evaluated the reliability of each measure by study year and examined the number of hospitals meeting different thresholds of reliability.

RESULTS:
We included 66,571 elective lumbar fusion surgeries performed at 244 hospitals. 12.0% of patients experienced a complication within 90 days of surgery, including 7.8% with a serious complication. The median reliability of 90-day cost ranged from 0.97-0.99 across study years. By comparison, the median reliability for the overall complication metric ranged from 0.22-0.44, and the reliability of the serious complication measure ranged from 0.30-0.49 across the study years. While some low-volume hospitals had reliabilities for cost as low as 0.51, at least 96% of hospitals had high (>0.7) reliability for cost in any year. By comparison, the reliability of the overall and serious complication rate varied substantially by hospital case volume, and only 0-9% and 0-11% of hospitals had high (>0.7) reliability in any year.

CONCLUSION:
90-day inpatient costs following lumbar fusion for spondylolisthesis are highly reliable for assessing variation across hospitals, whereas overall and serious complications are only moderately reliable for profiling performance.
160 Administrative Data are Unreliable for Ranking Hospital Performance Based on Serious Complications After Spine Fusion
Authors: Greenberg Jacob K. , Olsen Margaret , Poe John , Dibble Christopher , Yamaguchi Ken , Kelly Michael , Hall Bruce , Ray Zack 
Published: March 2022

INTRODUCTION:
While payers are increasingly focused on implementing pay- for-performance measures, quality metrics must reliably reflect true differences in performance among the hospitals profiled.

METHODS:
tWe used State Inpatient Databases from nine states to characterize serious complications after elective cervical and thoracolumbar fusion. Hierarchical logistic regression was used to risk-adjust differences in case mix, along with variability from low case volumes. The statistical reliability of this risk-stratified complication rate (RSCR) was assessed as the amount of variation between hospitals relative to the total amount of variation for each measure, calculated separately by fusion type and year. In other words, statistical reliability reflected the amount of variation between hospitals that was not due to chance alone. Finally, we estimated the proportion of hospitals that had sufficient case volumes to obtain reliable (>0.7) complication estimates.

RESULTS:
From 2010-2017 we identified 154,078 cervical and 213,133 thoracolumbar fusion surgeries. 4.2% of cervical fusion patients had a serious complication, and the median RSCR increased from 4.2% in 2010 to 5.5% in 2017. The reliability of the RSCR for cervical fusion was poor and varied substantially by year (range 0.04-0.28). Overall, 7.7% of thoracolumbar fusion patients experienced a serious complication, and the median RSCR varied from 6.8%-8.0% during the study period. Although still modest, the RSCR reliability was higher for thoracolumbar fusion (range 0.16-0.43). Depending on the study year, 0-4.5% of hospitals had sufficient cervical fusion case volume to report reliable (> 0.7) estimates, whereas 15-36% of hospitals reached this threshold for thoracolumbar fusion.

CONCLUSION:
A metric of serious complications was unreliable for benchmarking cervical fusion outcomes and only modestly reliable for thoracolumbar fusion.
164 Racial Disparities in Surgical Recommendations for Primary Central Nervous System Tumors
Authors: Butterfield Jack , Golzarian Sina , Johnson Reid A. , Fellows Emily , Dhawan Sanjay , Marcotte Erin , Venteicher Andrew S. 
Published: March 2022

INTRODUCTION:
Racial disparities in treatment and outcomes disproportionately affect patients of color in many surgical fields. There is limited research on these disparities within the field of neurosurgery and most studies report solely on outcomes, not management, of populations at a single institution.

METHODS:
The National Cancer Institute Surveillance, Epidemiology, and End Results database (1971-2015) was used to collect demographic and clinical variables on patients with meningioma (n = 63674), glioblastoma (n = 35258), pituitary adenoma (n = 27506), vestibular schwannoma (n = 11525), astrocytoma (n = 5402), or oligodendroglioma (n = 3977). Univariate and multivariate logistic regression were performed to identify factors independently associated with recommendation against surgical resection.

RESULTS:
Independent of age at diagnosis, sex, tumor histology, grade, and size, Black patients with meningioma (OR 1.20, 95% CI 1.12-1.27, p < 0.001), glioblastoma (OR 1.15, 95% CI 1.02-1.30, p = 0.023), pituitary adenoma (OR 1.19, 95% CI 1.11-1.28, p < 0.001), and vestibular schwannoma (OR 1.56, 95% CI 1.26-1.93, p < 0.001) were more likely to be recommended against surgical resection compared to White patients. Results were consistent after accounting for patient insurance status and rural-urban continuum code for the county of treatment.

CONCLUSION:
On review of the NCI SEER database, Black patients were more likely to be recommended against surgery compared to White patients for a number of primary CNS neoplasms, independent of clinical and demographic factors. Further research is needed to identify specific contributions to this inequity.
165 National Reduction in Cerebral Arteriovenous Malformation Treatment Correlated with Increased Rupture Incidence
Authors: Luther Evan , McCarthy David J. , Burks Joshua D. , Govindarajan Vaidya , Silva Michael A. , Lang Michael J. , Gross Bradley A. , Starke Robert M. 
Published: March 2022

INTRODUCTION:
In 2014 “A Randomized Trial of Unruptured Brain Arteriovenous Malformations” (ARUBA) concluded that medical management alone was superior to interventional therapy for adult patients with unruptured brain arteriovenous malformations (AVMs).

METHODS:
154,297 weighted AVM admissions were identified in the United States from 2003 to 2017 in the National Inpatient Sample. Annual AVM intervention and rupture rates were computed and multivariable logistic regression assessed likelihood of AVM intervention pre- and post-ARUBA. Segmented regression identified significant change-points and fitted segmented linear models for annual intervention and rupture rates. Pearson and Spearman coefficients examined correlation between annual AVM intervention and rupture rates.

RESULTS:
For unruptured AVMs, intervention proportion and likelihood of receiving intervention decreased following ARUBA (28.1% to 22.3%, P < 0.0001; adjusted odds ratio 0.857, 95% CI 0.751-0.977, P = 0.02). Ruptured AVM admissions increased from 14.7% to 18.6% after ARUBA (P < 0.0001). Between 2003 and 2017, segmented linear regression identified one significant change-point in unruptured AVM intervention rate between 2014 and 2015. Average annual percent change for rupture incidence and intervention rate increased by 0.49% (P=0.0001) and decreased by 1.17% (P = 0.0001), respectively. Annual AVM intervention rates had a strong inverse correlation with annual AVM rupture incidence (Pearson coefficient = -0.82, P = 0.0002). In 2017, the annual AVM rupture rate (20.6%) surpassed the annual AVM intervention rate (19.7%) for the first time.

CONCLUSION:
Following ARUBA, the odds of intervention for unruptured AVMs have decreased while ruptured AVM incidence has increased. These findings are inversely correlated suggesting that less unruptured AVM treatments may lead to a substantial increase in AVM rupture incidence.
167 Reversible VWF Inhibitor Lyses MCA Occlusion 6 Hours after Large Vessel Occlusion Stroke
Authors: Zakeri Amanda S. , Wheeler Debra , Milks Michael , Kini Aarushi , Carfora Arianna , Joseph Matthew , Gnyawali Surya , Anderson Cole , Stork Taggart , Shujaat Mohammad , Nimjee Shahid M. 
Published: March 2022

INTRODUCTION:
Acute ischemic stroke (AIS) is the leading cause of combined morbidity and mortality worldwide. Recombinant tissue plasminogen activator (rtPA) represents the only approved pharmacological treatment for AIS but is limited to treating those within 4.5 hours of stroke onset because of the risk of intracranial hemorrhage. Moreover, it is ineffective in treating large vessel occlusion (LVO) stroke. For this population, endovascular mechanical thrombectomy (MT) effectively recanalizes the occlusion but is limited to highly-specialized hospitals, leaving the vast majority without timely acute treatment.

METHODS:
Utilizing a canine embolic middle cerebral artery occlusion (eMCAO) model of LVO stroke, we assessed DTRI-031 on vessel recanalization after 6 hours of LVO stroke by digital subtraction angiography (DSA). We also measured the effect of recanalization on infarct volume (efficacy) and hemorrhage (safety) using magnetic resonance imaging (MRI). Finally, we assessed the ability of DTRI-025, an oligonucleotide that binds DTRI-031 to reverse DTRI-031 activity.

RESULTS:
DTRI-031 administration after 6 hours of LVO stroke resulted in >TICI 2A in 62.5% and >TICI 2B in 50% of canines (n = 8). Negative control group demonstrated no revascularization (n = 7). Recanalization resulted in reduced infarct volume compared to negative control (p < 0.05, unpaired t-test). None of the animals that received DTRI-031 had intracranial hemorrhage on MRI. Finally, DTRI-025 completely reversed the activity of DTRI-031 within 5 minutes of administration in both whole blood impedance aggregometry (WBA) and PFA-100.

CONCLUSION:
DTRI-031 effectively recanalizes LVO after 6 hours of stroke onset with reduced infarct volume and no incidence of hemorrhage. DTRI-025 rapidly reverses DTRI-031. This drug/reversal agent combination represents a robust yet safe approach to treat AIS.
168 International Study of Intracranial Aneurysm Embolization Using the Woven EndoBridge (WEB) Device: Results of the WorldWideWEB Consortium
Authors: Adeeb Nimer 
Published: March 2022

INTRODUCTION:
Pooled data from several registries have shown satisfactory efficacy of the WEB device to treat wide-neck aneurysms. The present study is the most extensive multi-center collaboration that endeavors to investigate the angiographic and clinical outcomes of real-world treatment of intracranial aneurysms with the device.

METHODS:
The World-Wide-WEB consortium is a retrospective multicenter collaboration of international centers with no limitation on aneurysm location or rupture status. Both bifurcation and sidewall aneurysms were included. Angiographic and clinical outcomes and complications were assessed among all consecutive patients along with determinants of adequate aneurysm occlusion (i.e. complete occlusion or neck remnant).

RESULTS:
The cumulative population comprised 674 patients (median age 61.3 years; 71.3% female) with 686 intracranial aneurysms. MCA bifurcation (30.2%) was the most common location. Adequate occlusion was observed in 85.7% of aneurysms at the last follow-up. Aneurysm retreatment was required in 7.9% of aneurysms. Thromboembolic complications were encountered in 7.6% of patients, but only 2.0% had permanent neurological deficits, while 3.1% had hemorrhagic complications. We identified subarachnoid hemorrhage, immediate remnant aneurysm (as compared to complete occlusion), and minor compaction or major compaction (as compared to no compaction) as significant determinants for lower rates of adequate aneurysm occlusion on last follow up (p < 0.01).

CONCLUSION:
This report suggests an adequate efficacy and safety profile of the WEB comparableto the currently availablesurgical andotherendovascular techniques fortreatment ofintracranial aneurysms.