bluuebunny/crossref_metadata_2025_split huggingface dataset:
381 Repeated Opening of the Blood-Brain Barrier With the Skull-implantable SonoCloud-9 (SC9) Device: Phase 1 Trial of Nab-Paclitaxel and SC9 in Recurrent Glioblastoma
Authors: Sonabend Adam M. , Gould Andrew , Luan Yu , Hou Ye , Chen Le , Kobayashi Mikoto , Castro Brandyn , Zhang Daniel , Korobova Farida , Amidei Christina , Youngblood Mark William , Bebawy John Patrick , Liu Benjamin P. , Horbinski Craig , Desseaux Carole , Helenowski Irene , Zhang Hui , Muzzio Miguel , Yue Feng , Caney Michael , Stupp Roger 
Published: March 2023

INTRODUCTION:
The blood-brain barrier (BBB) is a major impediment to pharmacological treatment of gliomas, as these infiltrate the brain. Low-intensity pulsed ultrasound with concomitant intravenous microbubbles (LIPU/MB), opens the BBB.

METHODS:
To perform LIPU/MB-based BBB opening prior to ABX infusions, we used a novel 6 x 6 cm device with 9 ultrasound emitters (SC9) that is implanted in a skull window after tumor resection. A Phase 1 dose-escalation trial using Bayesian adaptive design was initiated at our institution (NCT04528680). Patients with recurrent operable glioblastoma, a WHO PS ≤ 2 and normal bone marrow and organ function were eligible. After tumor resection and implantation of SC9, repeated cycles of BBB opening by LIPU/MB immediately followed by ABX, were performed Q3W. Intraoperative LIPU/MB and low dose ABX was given prior to tumor resection for pharmacokinetic studies.

RESULTS:
Seventeen patients were enrolled, and dose levels 40-260 mg/m2 were investigated. At dose of 260 mgm2, a grade 3 reversible taxane-associated encephalopathy was observed in one patient, considered a dose-limiting toxicity. The patient continued treatment at a lower dose in subsequent cycles. A second patient exhibited encephalopathy on cycle 2. Pharmacokinetic studies showed that ABX tissue concentrations in non-enhancing peri-tumoral brain were increased 3.7-fold after LIPU/MB. sc-RNA-sequencing showed transcriptional dysregulation of membrane transporters, pathways related to trans-cytosis as well as cell-cell and cell-matrix adhesion. Ultrastructural analysis of brain capillaries revealed that LIPU/MB led to time-dependent emergence of vesicles in endothelial cells

CONCLUSIONS:
The LIPU/MB using skull-implantable ultrasound enhances the penetration of ABX in large regions of the brain, a procedure that can be performed repeatedly and safely. LIPU-based BBB opening leads to ultrastructural transcriptional alterations in brain endothelium.

Funding:
NIH/NCI 1R01CA245969-01A1, CarThera (SC9 devices), BMS/Celgene (Abraxane®).
387 ICU Utilization in Elective Endovascular Treatment of Unruptured Intracranial Aneurysms
Authors: Padmanaban Varun , Cohrs Austin , Jareczek Francis , Hazard Sprague , Zacko Chris Christopher , Church Ephraim W. , Simon Scott Douglas , Cockroft Kevin M. , Leslie Douglas , Wilkinson D. Andrew 
Published: March 2023

INTRODUCTION:
Evidence suggests routine post-operative intensive care unit (ICU) admission in high-risk neurosurgical procedures, including endovascular treatment of unruptured intracranial aneurysms (UIA), may be unnecessary, though current practice patterns are undescribed. We sought to evaluate trends in ICU utilization in patients undergoing elective endovascular repair of UIA in the United States.

METHODS:
This is a retrospective cohort study utilizing commercial claims from a nationwide longitudinal database of multiple payors in the U.S. (MarketScan) to evaluate ICU use in patients undergoing elective, endovascular repair of UIA between 2005 and 2019. Our initial cohort was defined using diagnosis codes and CPT procedural codes. Patients with ruptured aneurysms were excluded, and the remaining unruptured patients were separated by ICU revenue codes to identify those who were likely admitted to the ICU post-operatively. A combination of diagnosis codes and procedural codes were utilized to evaluate demographics, pre-operative comorbidities, post-procedural complications, and discharge status. Cost analysis was also performed.

RESULTS:
Of 6218 patients who underwent elective endovascular treatment of UIA, 78.6% (4890) of patients were placed in the ICU post-operatively, and this percentage remained stable over the study period. No differences in age, sex, comorbidity scores, or smoking history were found between patients admitted to the ICU versus those admitted to the floor. ICU utilization was more common in urban locations (p < 0.001). The average total payment was higher in patients admitted to the ICU post-operatively ($46,429 versus $40,552, p < 0.0001).

CONCLUSIONS:
Almost 80% of patients undergoing elective endovascular repair of UIA are admitted to the ICU postoperatively, despite multiple studies suggesting this practice is unnecessary. Costs are significantly higher in patients utilizing the ICU. Reducing routine ICU use in this subgroup of patients may reduce costs and resource utilization in a safe manner.
392 A Morphological Study of Non-Stenotic Carotid Atheromas Causing Recurrent Strokes: Chronicle of Disruption and Stabilization
Authors: Madhani Sarosh Irfan , Larco Jorge Arturo , Abbasi Mehdi , Liu Yang , Shahid Adnan , Reade Quinton , Seibel Eric , Savastano Luis 
Published: March 2023

INTRODUCTION:
Symptomatic non-stenotic carotid (SyNC) artery disease is a recognized etiology of ischemic strokes with a putative thromboembolic mechanism. To date, the structural phenotypes expressed at the lumen/wall interface of these lesions are not completely understood resulting in misdiagnosis and hindering the development of targeted therapies.

METHODS:
After IRB approval, en block endarterectomy specimen were obtained from patients with recurrent strokes from SyNC (n=9). Additionally, segments of superficial temporal artery (STA) of patients undergoing cerebral artery bypass surgeries were obtained as controls (n=3). The endovascular surfaces of the samples were imaged with laser microangioscopy and scanning electron microscopy (SEM). Images were benchmarked with histological sections and immunohistochemistry (IHC).

RESULTS:
Normal endothelial surfaces in STA were light pink, smooth and homogenous by angioscopy with typical cobblestone endothelial pattern. Features recognized as those associated with plaque disruption and thrombosis were de-endothelialization, inflammatory infiltrates within and under the endothelium, delamination (flaps oriented to the flow) with superficial intimal hemorrhages, plaque erosion and disruption of the fibrous cap with fissuring, ulceration, excavation and plaque hemorrhage. Additionally, cellular and acellular structures actively involved in plaque stabilization, seen on SEM and confirmed with histology and IHC, were also identified including activated platelets, fibrin band, bridges and webs, neutrophil extracellular traps and endothelial progenitor cells.

CONCLUSIONS:
This ultrastructural study of the vascular surface of SyNC specimens reveals concurrent phenotypes of flow-dependent disruption and stabilization that could become new imaging biomarkers and enable the development of targeted therapies.
395 The “Hub-Spoke” Telemedicine Model in a Large Cohort of Stroke Patients
Authors: El Naamani Kareem , Herial Nabeel , Abbas Rawad , Sioutas Georgios Georgios , Amllay Abdelaziz , Munoz Alfredo , Morse Charles , Moylan Daniel , Joffe Daniel , Knapp Michael , Tjoumakaris Stavropoula I. , Gooch Michael Reid , lRosenwasser Robert H. , Jabbour Pascal 
Published: March 2023

INTRODUCTION:
Stroke is a leading cause of death and disability worldwide. According to the World Health Organization, stroke patients should be treated in dedicated stroke units. However, stroke units require multidisciplinary stroke expertise which is usually scarce in rural areas.

METHODS:
This is a retrospective single-center study encompassing patients suffering from strokes and receiving pre-hospital and in-hospital tele-stroke expertise based on a spoke/hub stroke network. Data from 38 hospital networks between December 2014 and January 2018 were collected.

RESULTS:
The study cohort consisted of 9702 patients. The majority were females (n = 3556, 55.3%) and the mean age was 67 (67 +16.7, 66.7 - 67.4, 26 -122). Of all patients, tissue plasminogen activator (tPA) was recommended in 1313 (16.3%) patients, and from these, 810 (61.7%) patients were actually given tPA. As for endovascular intervention, only 187 (2.3%) patients underwent mechanical thrombectomy at our institution.

CONCLUSIONS:
Tele-stroke networks have proven to be a pivotal development in the treatment of strokes, especially those that are remote. With the additional expertise and the shorter duration from onset to diagnosis to treatment, these networks have substantially improved patient care and decreased healthcare costs, avoiding unnecessary transfers from spoke hospitals to hub.
398 Towards Catheter-Clot Engagement Detection Via Classification of Vacuum and Motion Signature During Aspiration Thrombectomy
Authors: Veliky Madison , Lawson Jared , Chitale Rohan V. , Simaan Nabil 
Published: March 2023

INTRODUCTION:
While acute ischemic stroke caused by large vessel occlusion is effectively treated with aspiration thrombectomy, procedural success depends on the quality of engagement between the catheter tip and the thrombus. Currently, there is no method to identify whether the catheter tip is truly in contact with the clot surface. Poor thrombus engagement can result in failure of recanalization.

METHODS:
An in vitro arterial occlusion was modeled with Tygon tubing representing the blood vessel and a synthetic thrombus made from TrueClot simulants. A 6Fr microcatheter was controllably inserted into the mock vessel until it contacted the synthetic thrombus. A motorized syringe and pressure sensor were connected proximally to the catheter to precisely control and measure the cyclic vacuum excitation in the catheter. The cyclic vacuum excitation was performed with a stroke of ±0.5 mm at 2 Hz, 4 Hz, and 8 Hz at catheter-clot distances of 150 mm, 20 mm, 10 mm, 5 mm, and in contact on 17 different clot models. Control and sensing data was collected at 1000 Hz frequency. For each catheter-clot distance, 1000 vacuum measurements were collected and pressure traces were saved. The change in the pressure mean per a change in insertion depth of the catheter was used to train a support vector machine (SVM) classifier that confirms clot contact.

RESULTS:
Using 30% of the clot model samples to train the SVM classifier and the remaining samples for validation, the quality of classification was determined. The accuracy (and F1 score) of clot detection at 2 Hz, 4 Hz, and 8 Hz were 98.31% (95.65%), 100% (100%), and 93.22% (80.00%) respectively.

CONCLUSIONS:
Accurate detection of catheter-clot contact is feasible via small excitation of the aspiration syringe and concurrent measurement of vacuum pressure.
409 Effect of Social Determinants of Health on Post-Discharge Adverse Outcomes After Surgical Resection of Meningioma
Authors: Wong Gunther , Tang Alan Ruigang , Guidry Bradley , Grisham Candace , McDermott Jake , Morone Peter J. , Thompson Reid C. , Chambless Lola Blackwell , Chotai Silky 
Published: March 2023

INTRODUCTION:
Understanding the role of social determinants of health (SDoH) is critical in informing preoperative care and postoperative follow-up for meningioma patients undergoing surgery.

METHODS:
A retrospective cohort study of adults presenting for meningioma resection from 1999-2020 was conducted. Primary outcomes included recurrence, readmission, and LTF (6-month and total). The main exposure of interest was Area Deprivation Index (ADI), a composite score of socioeconomic disadvantages. Additional SDoH factors analyzed included drive time to the hospital, insurance, and race. Multivariable logistic regression analyses for LTF and Cox regression for recurrence- and readmission-free survival were conducted. Covariates included age, WHO grade, and extent of resection.

RESULTS:
In total, 736 patients were included. Recurrence was observed in 90 patients, and 99 patients were readmitted following discharge. 121 patients missed initial and 6-month follow-up, but 107 of those eventually followed-up after six months. Fourteen patients were entirely LTF. ADI (OR = 1.11 per 10-point increase, 95% CI 1.02-1.21, p = 0.017) and drive time (OR = 1.03 per 30-minute increase, 95% CI 1-1.06, p = 0.022) predicted 6-month LTF. Drive time predicted complete LTF (OR = 1.04 per 30-minute increase, 95% CI 1-1.07, p = 0.017). Medicare/Military insurance predicted lower recurrence risk (HR = 0.43, 95% CI 0.23-0.81, p = 0.009) and higher readmission risk (HR = 2.00, 95% CI 1.17-3.41, p = 0.011). Other SDoH factors were not associated with recurrence or readmission. Lower WHO grade predicted lower recurrence risk (HR = 0.5, 95% CI 0.33-0.78, p = 0.002), while age (HR = 0.75 per 10-year increase, 95% CI 0.62-0.89, p < 0.001) and gross total resection (HR = 0.56, 95% CI 0.35-0.9, p = 0.016) predicted lower readmission risk.

CONCLUSIONS:
Socioeconomically disadvantaged neighborhoods and further distance from the hospital were barriers to follow-up after meningioma resection. Other SDoH associated with readmission and recurrence are reported. Individualized follow-up plans should consider these SDoH to ensure care continuity and improve outcomes.
410 Treatment of Idiopathic Normal Pressure Hydrocephalus With a Novel Programmable Valve With Gravitational Unit: Prospective Evaluation of Efficacy, Safety and Costs
Authors: Reis Rodolfo , Yamashita Renata , Fontoura Solla Davi Jorge , Ramin Laís , Almeida de Oliveira Teixeira Manoel Jacobsen , Gomes Pinto Fernando Campos 
Published: March 2023

INTRODUCTION:
Programmable valves provide an equal or superior neurological outcome when compared to fixed pressure ones, with fewer complications, in treating idiopathic normal pressure hydrocephalus (iNPH) patients. Long-term costs of these treatments have not been properly compared in literature.

METHODS:
A prospective cohort of iNPH patients treated with programmable valve between January 2018 and May 2020 was compared to a historical cohort of iNPH patients treated with fixed pressure valve from January 2016 through December 2017. Our primary outcome was the mean cost of treating iNPH up to one year. Cost variables assessed included number of surgeries, length of ICU and hospital stay, and number of imaging tests. Efficacy in treating iNPH, measured by mean NPH Japanese Scale, and safety, measured by complications rates, were assessed as secondary outcomes.

RESULTS:
A total of 19 patients were analyzed in each group (mean age 75 years, the majority male). Comorbidities and clinical presentation were similar between groups. Both fixed pressure and programmable valve patients had neurological improvement over time (p < 0.001), but no difference was seen between groups (p = 0.104). The fixed pressure valve group had more complications than programmable valve group (52.6% vs 10.5%, respectively, p = 0.013). Annual treatment cost per patient was US$ 3,820 ± 2,231 in the fixed pressure valve group and US$ 3,108 ± 553 in the programmable valve group. Mean difference was US$712 (95% CI, 393 – 1,805) in favor of the programmable valve group.

CONCLUSIONS:
The novel programmable valve with gravitational unit had one-year treatment cost not higher than that of fixed-pressure valve, and resulted in similar efficacy and fewer complications.
414 Competitive Advantage: An Analysis of Matched and Unmatched United States Neurological Surgery Residency Applicants From 2009-2021
Authors: Goldman Liam , Iyer Ankitha Mahesh , Barpujari Awinita , Rogers James Louis , Reddy Vamsi , Johnson Jeremiah N. 
Published: March 2023

INTRODUCTION:
National Resident Matching Program releases a detailed report of residency match statistics for each specialty. Securing a training position in a United States neurological surgery residency program is notoriously competitive, and the subspecialty has long maintained a match rate much lower than other specialties. There remains a paucity of recently studied longitudinal trends in academic and extracurricular characteristics of successfully matched neurological surgery residency applicants.

METHODS:
Residency applicant self-reported data, obtained from the American Association of Medical Colleges Electronic Residency Application Service, were collected from yearly “Results and Data: Main Residency Match” (2009-2021) and biennial “Charting Outcomes in the Match” (2009-2020) National Residency Match Program summary reports.

RESULTS:
From 2009-2021, the number of neurological surgery residency programs and positions increased from 97 to 115 and 191 to 234, respectively. Matched applicants’ average United States Medical Licensing Exam (USMLE) Step 1 scores significantly increased (239 to 248; p = 0.01332), while average USMLE Step 2 Clinical Knowledge scores rose (237 to 252; p = 0.05682) during the study period. Average number of distinct research experiences among matched applicants increased (3.3 to 6.1; p = 0.5398), while the average number of abstracts, presentations, and publications increased from 7.8 to 23.4 (p = 0.0746). Lastly, Alpha Omega Alpha (AOA) membership (p = 0.00077) and percentage graduating from a top National Institutes of Health-funded medical school (p = 0.00396) significantly differed between matched and unmatched neurological surgery residency applicants.

CONCLUSIONS:
Matched neurological surgery residency applicants had significantly fewer average number of distinct specialties ranked, higher USMLE Step 1 scores, greater AOA membership, and more frequently graduated from top 40 NIH-funded medical schools than their unmatched counterparts. Additional research considering applicant-level intersectional data is warranted to further understand the match process.
415 Gender Differences in Operative Autonomy Using the Surgical Autonomy Program
Authors: Kirsch Elayna P. , Suarez Alexander , Venkatraman Vishal , Murphy Kelly Ryan , McDaniel Kate , Dharmapurikar Rajeev , Lad Nandan P. , Haglund Michael M. 
Published: March 2023

INTRODUCTION:
While efforts to recruit females into surgical fields have increased, gender differences in surgical training exist.

METHODS:
The SAP divides a surgical case into four parts, or zones of proximal development (ZPD). For each ZPD, residents are evaluated on a 4-tier autonomy scale (TAGS scale). Using logistic regression analysis, we evaluated neurosurgery residents at Duke University Hospital from July 2017-July 2021 to compare differences in male and female trainee autonomy as rated by both attendings and residents.

RESULTS:
There were a total of 4,441 cases logged by 26 different residents and 30 attendings. 69% of residents were male (n = 18) and 31% (n = 8) were female. An ordinal regression analysis showed that female residents were given less autonomy than males by attendings (OR 0.59, 0.51-0.69 95% CI, p < 0.001). Females were also less likely to focus on a more complex ZPD (OR 0.53, 95% CI 0.46-0.61, p < 0.001). Based on self-evaluation, female residents rated their autonomy lower than males (OR 0.71, 0.61-0.82 95% CI, p < 0.001). Faculty provided greater intraoperative feedback in cases with female residents (84%, n = 539) compared to male residents (79%, n = 1,875) (X2 = 7.52, df = 1, p < 0.01). Female and male residents were fully autonomous on a similar proportion of cases in post-graduate year seven (73% and 72%, respectively).

CONCLUSIONS:
Female residents were given less autonomy compared to their male counterparts for index neurosurgical cases and were less likely to focus on a more complex portion of a case. Female residents were more self-critical, though received greater significant intraoperative feedback. Nonetheless, females and males were fully autonomous on a similar number of cases in their final residency year. Increased efforts are needed to address the gender gap within surgical education.
422 Utilizing Situational Judgment Test in Neurosurgery Residency Online Interviews
Authors: Feng Rui , Subramaniam Varun , Mocco J D. , Kellner Christopher P. , Shrivastava Raj K. 
Published: March 2023

INTRODUCTION:
Neurosurgery residency selection is heavily reliant on pre-residency factors and unstructured interviews. These metrics, however, have not been shown to reliably predict residency performance, and have potential to introduce bias and discrimination. Outside of medicine, the science of selection is much better developed, and methods such as structured interviews, situational judgment tests (SJT), and personality assessments are routinely used with robust evidence for efficacy and reliability at predicting job performance.

METHODS:
We designed a set of 4 SJT questions mimicking common situations a neurosurgery resident would encounter during residency. Each question had individualized grading rubrics scored on a scale of 1 to 4. For the 2021 residency application cycle, our program incorporated these SJT questions as part of the online interview process. Four volunteer faculty interview pairs delivered one question each for every candidate, and recorded the scores. Other traditional evaluation metrics from the candidate’s application and interview were also collected post interview.

RESULTS:
All 44 interview candidates applying to our program during the 2021 cycle were assessed. Due to time constraints, the number of questions each candidate responded to varied from 2 to 3. The average score was 3.6 (SD 0.44, range 2-4). The SJT score was not associated with USMLE Step 1 score (p = 0.31), number of publications (p = 0.42), or letter of recommendation score (p = 0.21). The SJT scores had a moderate positive correlation with personality on interview (r = 0.42, p < 0.01), and overall interview score (r = 0.30, p = 0.04).

CONCLUSIONS:
It is feasible to incorporate SJT questions into the neurosurgery resident online interview process. They may provide objective metrics independent of academic and research abilities. Further investigations with long term follow up is needed to see if SJT can be validated and correlated with residency performance.
431 An Observational Analysis of Randomized Controlled Trials (RCTs) Discontinuation and Non-Publication in Spine Disease
Authors: Tiefenbach Jakov , Demetriades Andreas K. , Park Jay 
Published: March 2023

INTRODUCTION:
Incompleteness and non-publication of Randomized Controlled Trials (RCTs) have been increasingly reported in the literature. This is a significant concern as RCTs demand monumental amounts of healthcare resources leading to wastage. Most importantly, both under-reporting and non-publication distorts evidence landscape and obscures rationale behind clinical decisions.

METHODS:
A list of RCTs was obtained from the U.S National Library of Medicine ClinicalTrials.gov database from January 1st, 2013, to December 31st, 2020. Two independent authors excluded all non-RCTs, trials unrelated to spinal diseases, and trials that are in or before the recruitment phase. We extracted the progress status, sources of funding, number of centers, type of intervention, principal investigator’s department affiliation, publication status, location, reason for discontinuation, publication date, and subtopics.

RESULTS:
A total of 112 trials were included in the study. Twenty-five (22%) trials were discontinued early, with slow recruitment being the major reason (38%). Only fifty-six (50%) of the trials were published in peer-reviewed journals. Trial discontinuation was much higher in trials registered in the United States (US) compared to other countries (P = 0.009). There were 11 (23.4%) industry-sponsored and 14 (21.5%) non-industry-sponsored studies that remained uncompleted. Over the study period, only 20% of the trials were fully compliant with the FDA reporting requirements.

CONCLUSIONS:
Nearly a quarter of all trials in spinal disorders were discontinued. Half of the trials were unpublished. These rates remain worrisome from an ethical and financial perspective. Both under-reporting and non-publication adversely affect patient safety and waste valuable healthcare resources. An organized effort is needed to address this important issue and improve the rates of trial completion and publication.