bluuebunny/crossref_metadata_2025_split huggingface dataset:
389 Combination Therapy With Paclitaxel, Carboplatin, and Low-Intensity Ultrasound for Recurrent Glioblastoma: Rationale for Ongoing Phase II Clinical Trial
Authors: Habashy Karl , Dmello Crismita , Chen Li , Arrieta Victor Andrés , Kim Kwang-Soo , Gould Andrew , Canney Michael , Stupp Roger , Sonabend Adam M. 
Published: March 2024

INTRODUCTION:
We recently participated in Phase 1/2 clinical trials where patients with recurrent glioblastoma received surgery for resection of the tumor followed by implantation of an ultrasound device (SonoCloud-9, Carthera, Lyon, France) into a window in the skull for subsequent repeated blood-brain barrier (BBB) opening and concomitant delivery of chemotherapy. Intraoperative experiments demonstrated a 4-6-fold increase in the brain concentration of paclitaxel (NCT04528680) and carboplatin (NCT03744026) after BBB disruption.

METHODS:
We analyzed the cytotoxicity of paclitaxel and carboplatin in vitro against five human cell lines and six patient-derived xenografts (PDX) as monotherapy and in combination at concentrations derived from our human intraoperative pharmacokinetic studies. Synergy was assessed using the Loewe model and survival benefit was evaluated in two xenografts where drugs were delivered with ultrasound. We also examined the effects on cell cycle progression, DNA damage, and apoptosis.

RESULTS:
Cell lines exhibited non-overlapping susceptibility to paclitaxel and carboplatin, with 27% being exclusively susceptible to one drug. The combination covered 81% of cell lines, demonstrating synergy in 55% of cell lines. Notably, paclitaxel, carboplatin, and ultrasound proved more effective than monotherapy in two xenograft models. Combination therapy led to distinct effects on cell cycle progression and enhanced DNA damage and apoptosis.

CONCLUSIONS:
Combination therapy may be more effective than monotherapy, as has been shown in other cancers, due to synergy and independent susceptibility to each drug in glioma cell lines. This strategy is currently under investigation in an ongoing phase II clinical trial to further evaluate the safety and efficacy of this approach in patients with recurrent glioblastoma (NCT04528680).
394 Predicting STA-MCA Anastomosis Patency Using FLOW800
Authors: Lee Sangwon Karl , Liu Albert , Wiggan Daniel , Rabbin-Birnbaum Corinne , Alexander Alber Daniel , Rutledge Caleb , Russin Jonathan , Nossek Erez 
Published: March 2024

INTRODUCTION:
STA-MCA bypass is the “work horse” for cerebral flow augmentation that yields high rates of anastomosis patency. However, the persistence of no-flow due to insufficient local demand presents a challenge. Here, we assessed intraoperative real-time hemodynamics measured by ICG-based FLOW800 to characterize risk and predict patency prior to anastomosis, aiding surgeons in choosing the optimal recipient and anastomosis site.

METHODS:
A retrospective and exploratory data analysis of 39 patients were conducted using FLOW800 software to assess 4 regions of interest (proximal/distal recipient and adjacent/remote gyrus) for 4 hemodynamic parameters: speed, delay, rise-time, and time-to-peak. Medical records were used to classify patients into flow and no-flow groups based on immediate or long-term anastomosis patency. Pre-anastomosis hemodynamics were compared between the two groups via univariate and multivariate analysis. Principal Component Analysis (PCA) was used to identify “high-risk” and “low-risk” groups for no-flow.

RESULTS:
35 patients demonstrated immediate flow post-revascularization and were compared to 4 patients with immediate or long-term no-flow post-revascularization. No-flow groups had significantly greater Proximal Recipient Speed (238.3 ± 120.8) and Distal Recipient Speed (241.0 ± 117.0) than the flow group (138.5 ± 93.6; 142.1 ± 103.8, p < 0.05). Based on PCA, a “high-risk” group (n = 10) including no-flow patients was characterized by high flow speed, and a “low-risk” (n = 6) for opposite parameters. Patients with follow-ups in the “low-risk” group maintained robust flow (4/4), whereas patients with follow-up in the “high-risk" group demonstrated reduced or absent flow (5/7).

CONCLUSIONS:
Our results suggest that high recipient speed measured intraoperatively elevates the risk of no patency or reduced flow, potentially due to reduced local demand. Continued FLOW800-based ROI metric analysis could guide intraoperative decision making of specific recipient and anastomosis site selection.
421 GPT-4 Artificial Intelligence Model Outperforms ChatGPT, Medical Students, and Neurosurgery Residents on Neurosurgery Written Board-Like Questions
Authors: Guerra Gage , Hofmann Hayden , Sobhani Sina , Hofmann Grady , Gomez David , Soroudi Daniel , Hopkins Benjamin , Dallas Jonathan , Pangal Dhiraj J. , Cheok Stephanie , Nguyen Vincent , Mack William J. , Zada Gabriel 
Published: March 2024

INTRODUCTION:
Artificial intelligence (AI) and machine learning (ML) have transformed healthcare, with applications in various specialized medical fields. Neurosugery can benefit from AI in surgical planning, predicting patient outcomes, and analyzing neuroimaging data. GPT-4, an updated advanced language model by OpenAI with additional training parameters, has exhibited exceptional performance on standardized exams.

METHODS:
GPT-4's performance was examined on 643 Congress of Neurological Suregons (CNS) Self-Assessment Neurosurgery Exam (SANS) board-style questions from various neurosurgery subspecialities. Of those, 477 were text-based and 166 contained images. GPT-4 refused to answer 52 questions that contained no text. The remaining 591 questions were inputted into GPT-4, and its performance was evaluated based on first-time responses. Raw scores were analyzed across subspecialties and questions types, then compared to previous findings on ChatGPT performance against SANS users, medical students, and neurosurgery residents.

RESULTS:
GPT-4 attempted 91.9% of CNS SANS questions and achieved 76.6% accuracy. The model's accuracy increased to 79.0% for text-only questions. GPT-4 outperformed ChatGPT across all neurosurgery categories, scoring highest in Pain/Peripheral Nerve (84%) and lowest in Spine (73%). The model exceeded the performance of medical students (26.3%), neurosurgery residents (61.5%), and the national average of SANS users (69.3%) across all categories.

CONCLUSIONS:
GPT-4 outperformed medical students, neurosurgery residents, and the national average of SANS users. The model's notable accuracy suggests potential applications in educational settings and clinical decision-making, enhancing provider efficicency, and improving patient care.
422 Novel Application of a Mixed-Reality Platform for Learning Neuroanatomy
Authors: Xiao Tianqi , Crofton Andrew , Sathishkumar Buvaneshwari , Enterline Rebecca , Wish-Baratz Susanne 
Published: March 2024

INTRODUCTION:
Neuroanatomy is a difficult and intimidating, but also foundational, subject for many medical specialties, especially Neurosurgery. Yet, few modern tools exist for teaching neuroanatomy. This pilot study sought to evaluate the effectiveness of a novel mixed-reality (MR) neuroanatomy visualization software and headset compared to traditional methods of instruction.

METHODS:
This was a prospective randomized cross-over study of volunteer participants in a graduate neuroanatomy course. Students were randomly assigned to either traditional (Group-1) or MR (Group-2) modalities for 2 of 4 course units. All students participated in class lectures. Following each lecture, the MR group conducted MR lab modules while the traditional group conducted traditional cadaveric dissections or yarn and paper lab activities. All students then took the traditional Unit-lab exam. The two groups switched modalities between units. For logistical reasons, the MR laboratory sessions were taught in a separate location than traditional modalities with a teaching assistant. Student opinions were collected via survey and exam results were analyzed via Student’s t-test.

RESULTS:
Thirty-seven students volunteered to participate, with 23 completing the study (Group-1 n = 11 and Group-2 n = 12). Twenty-one students completed the post-course survey. Performance on both lab exams did not differ significantly between traditional and MR groups (p > 0.05). Most participants (95.2%) recommended traditional neuroanatomy teaching methods while 47.6% recommended the MR application. However, 95.2% of participants agreed that using MR with traditional methods would be better than either separately.

CONCLUSIONS:
Students’ neuroanatomy exam performance did not differ based on laboratory modality, though students preferred the traditional approach. Most students acknowledged the potential usefulness of MR in addition to traditional modalities. Further studies with larger sample sizes and a single location and instructor are needed to more fully elucidate the value of MR in learning neuroanatomy.
426 Effect of Visuospatial Feedback Versus Numeric Scores on Neurosurgical Tumor Resection Skills Among Medical Students in Virtual Reality Simulation Randomized Control Trial
Authors: Yilmaz Recai , Fazlollahi Ali , Winkler-Schwartz Alexander , Del Maestro Rolando 
Published: March 2024

INTRODUCTION:
Virtual reality (VR) simulation can be implemented with various feedback modalities to optimize learners’ surgical skills acquisition. The systems can present benchmark scores as either a numeric report or a visuospatial performance assessment. In this context, the optimal feedback methodology to enhance learning remains undefined.

METHODS:
One hundred and twenty medical students (mean age [SD], 23.1 [3.6] years, 41% women) from four institutions were recruited to practice a simulated subpial tumor resection in five attempts. They were randomly assigned to receive one of four interventions between each attempt: (1) no feedback (n = 30), (2) numerical feedback (n = 30), (3) visual feedback (n = 29), or (4) visuospatial feedback (n = 31). Performance on the first task determined baseline. Skill was evaluated using previously established 14-expert performance benchmarks. The primary outcome was the number of performance benchmarks achieved throughout the five attempts.

RESULTS:
Participants in all feedback groups significantly improved their performance compared to baseline. Between-subjects comparison demonstrated a significant increase in the number of metrics achieved with visual (mean difference 1.80, p = 0.001) and visuospatial (mean difference 1.89, p < 0.001) feedback compared to control, and no significant increase with numeric assessment (mean difference 1.10, p = 0.093). In the third attempt, visual feedback was significantly superior to numeric assessment (mean difference 1.63, p = 0.016).

CONCLUSIONS:
Neurosurgical skill acquisition is enhanced with visual and visuospatial feedback in VR simulation training. These engaging modes of performance assessment result in more accelerated rate of benchmark acquisition compared to numerical scores alone. Further research is warranted to explore the potential benefits of visual and visuospatial feedback in other domains of surgical training.
436 Use of Ventriculostomy for Severe Traumatic Brain Injury Is Associated With Reduced Mortality Compared to Intraparenchymal Monitor Use: A Propensity Score-Matched Analysis
Authors: Mouchtouris Nikolaos , Luck Trevor , Yudkoff Clifford , Locke Katherine , Andrews Carrie Elizabeth , Shah Syed O. , Jallo Jack 
Published: March 2024

INTRODUCTION:
There is a lack of data on whether intracranial pressure (ICP)-guided therapy with an intraparenchymal fiberoptic monitor (IPM) or an external ventricular drain (EVD) leads to superior mortality outcomes.

METHODS:
Retrospective analysis of patients with severe TBI that required IPM or EVD placement for ICP-guided therapy from 1/1/2010-12/31/2020. The data was obtained from the Pennsylvania Trauma Systems Foundation (PTSF) registry.

RESULTS:
A total of 2,305 patients met the inclusion criteria with 1,048 (45.5%) IPM and 1,257 (54.5%) EVD placed. A craniectomy was performed in 47.0% of the patients in the IPM cohort and 66.0% of the EVD cohort (p < 0.001). Multivariable logistic regression analysis showed that older age (OR 1.03, p < 0.001), decreasing GCS score (OR 1.16, p < 0.001), requiring craniectomy (OR 1.22, p = 0.049), and an IPM (OR 1.40, p = 0.001) were significant predictors of mortality. A propensity score-matched analysis was performed, adjusting the cohorts for age, gender, race, GCS, ISS, and craniotomy. EVD use is associated with a significant 28% decrease in inpatient mortality when compared to IPM (OR 0.72, p < 0.001). Hospital length of stay was also significantly shorter in the EVD cohort (OR 0.86, p = 0.03).

CONCLUSIONS:
A significant decrease in mortality was associated with the use of EVD in comparison to IPM based on our propensity score-matched analysis. Further investigation.
456 Arm Flexion to Overcome Gaps for Primary Radial Nerve Repair: An Anatomic Study
Authors: Thum Jasmine A. , Bazarek Stanley , Brown Justin M. 
Published: March 2024

INTRODUCTION:
It is now well known that direct nerve repairs fare better than grafted nerve repairs. There is currently renewed interest in direct repair of nerves achieved by limb flexion followed by serial distraction as it is the least morbid and most easily implemented surgical technique to provide extra nerve excursion. This is especially simple in the upper extremity, which can be easily immobilized post-operatively in a sling.

METHODS:
Four fresh and 11 fixed cadaver arms with shoulder intact were dissected to determine the relationship between degrees of EF (ranged from 0-90 degrees EF) and nerve gap length overcome with proximal excursion of the distal nerve. Additional excursion from brachialis branch neurectomy was also assessed.

RESULTS:
We found an approximately linear relationship between EF and RN excursion. Compliance of fresh cadaveric nerves more closely approximated that of surgical tissue. In fresh cadavers, there was 3mm of RN excursion per 10 degrees EF in the proximal half of the arm, and 4 mm excursion per 10 degrees EF with neurectomy.

CONCLUSIONS:
Elbow flexion can significantly augment the ability to achieve an end-to-end repair of the RN. To simplify our findings, 90-degree EF should readily overcome a RN gap of 3.5 cm, and additional brachialis neurectomy allows for total RN excursion of 4.7 cm on average in the proximal arm with 90-degrees EF. Given nerve regeneration rates of 1-2 mm/day, we recommend 14-27 days prior to full elbow extension from a RN repair performed with 90-degree EF without neurectomy, and 18-36 days for repair at 90-degree EF with neurectomy.
463 Cervical Vertebral Bone Quality (C-VBQ) Score Independently Predicts Distal Junctional Kyphosis (DJK) Following Posterior Cervical Fusion
Authors: Aguirre Alexander Otilio , Soliman Mohamed A.R. , Kuo Cathleen , Ruggiero Nicco , Im Justin , Chintaluru Yaswanth , Khan Asham , Hess Ryan M. , Rho Kyungduk , Smolar David , Mullin Jeffrey Paul , Pollina John 
Published: March 2024

INTRODUCTION:
Posterior cervical fusion is the surgery of choice when fusing long segments of the cervical spine. However, due to the limited presence of this pathology, there is a paucity of data in the literature about the postoperative complication of distal junctional kyphosis (DJK).

METHODS:
A retrospective analysis of consecutive set of patients who underwent posterior cervical fusion at a single hospital between June 1, 2010 and May 31, 2020. Univariate analysis was completed between DJK and non-DJK groups, with multivariate regression completed for relevant clinical variables. Simple linear regression was completed to analyze correlation between the C-VBQ score and total degrees of kyphosis angle change.

RESULTS:
Ninety-three patients were identified, of whom 19 (20.4%) had DJK and 74 (79.6%) did not. The DJK group had a significantly greater number of patients with anemia than the non-DJK group (15.8% vs. 1.4%; P = .03). The DJK group had a significantly higher C-VBQ score than the non-DJK group (2.97 ± 0.40 vs. 2.26 ± 0.46; P < .001). A significant, positive correlation was found between the C-VBQ score and the total degrees of kyphosis angle change (r2 = 0.26, P < .001). On multivariate analysis, the C-VBQ score independently predicted DJK (OR, 1.50; 95% CI, 1.28-1.76; P < .001).

CONCLUSIONS:
We found that the C-VBQ score was an independent predictive factor of DJK after posterior cervical fusion.
465 Focused Ultrasound-Mediated Blood-Spinal Cord Barrier Permeabilization: A Promising Targeted Approach for Treating Chronic Spinal Cord Injury in Rat Models
Authors: Ghaith Abdul Karim , Moinuddin F.M. , Dhar Ashis , Zamanian Cameron , Nieves Antonio Bon , Windebank Anthony J. , Bydon Mohamad 
Published: March 2024

INTRODUCTION:
Focused ultrasound (FUS) with microbubble contrast agents can temporarily disrupt the blood-brain barrier (BBB), enabling drug delivery. FUS may also offer a minimally invasive method for delivering therapeutic agents to the affected area in chronic spinal cord injury (SCI) by transiently opening the blood-spinal cord barrier (BSCB).

METHODS:
Nine female Sprague-Dawley rats underwent a T9-T11 laminectomy with contusion SCI and were randomly allocated into FUS or control group. Three weeks later, FUS was administered intravenously with microbubbles. A pressure sweep was performed until ultra-harmonics were captured using a wideband hydrophone. We administered 2% Evans blue (EB) immediately after FUS confirmed the BSCB permeability. Transcardial perfusion was performed 2 hours later, and spinal cords were collected. Spectrophotometry was used to determine the EB concentration. Statistical analysis was performed using a student t-test.

RESULTS:
Five rats were treated with FUS while four were used as controls. Successful feedback control was achieved with FUS, and ultra-harmonics were observed in the FUS group at a mean peak pressure of 0.5 MPa. Macroscopic identification of EB in the spinal cord sections of animals exposed to FUS confirmed the localized opening of the BSCB. Spectrophotometry revealed an increase in EB concentration in the FUS group compared to controls: Mean EB concentration was 0.03 μg in the FUS group versus 0.016 μg in controls at 1-cm above the injury (p < 0.001); 0.27 μg versus 0.093 μg at the injury site (p < 0.001); and 0.25 μg versus 0.18 μg at 1-cm below the injury(p < 0.001).

CONCLUSIONS:
FUS increases the permeability of the BSCB in a chronic contusion SCI rat model. This suggests that FUS-mediated BSCB permeabilization may hold promise as a targeted approach for improving therapeutic outcomes in the treatment of chronic SCI.
509 Data-Driven Preoperative Hemoglobin Strata that Maximize the Likelihood of Blood Transfusion following Single-Level Lumbar Fusion Are Also Predictive of Major Complications and Deep Infections
Authors: Levy Hannon , Haft Mark , Agarwal Amil , Quan Theodore , Greenberg Marc , Raad Michael , Patel Tushar , Jain Amit 
Published: March 2024

INTRODUCTION:
Optimizing patients undergoing single-level lumbar spine fusion helps reduce the use of blood transfusions which are associated with an increased risk of major complications and deep infection. Current hemoglobin thresholds for anemia severity were published in 1968 and are not surgery specific.

METHODS:
A retrospective cohort analysis was performed using a national database to identify patients undergoing primary single-level lumbar fusion with recorded hemoglobin values 30 days before surgery. Stratum-specific likelihood ratio (SSLR) analysis defined sex-based hemoglobin strata associated with the risk of 90-day postoperative blood transfusion. Each stratum was propensity-score matched to the highest identified hemoglobin stratum. Incidence rates and risk of 90-day major complications and 2-year deep infection between strata were observed.

RESULTS:
For 90-day blood transfusion, SSLR identified three female [Strata, Likelihood ratio (5.0-10.9, 2.41; 11.0-12.4, 1.35; 12.5-17.0, 0.78)] and three male hemoglobin strata (5.0-11.9, 2.95; 12.0-13.4, 1.46; 13.5-13.9, 0.71). Increased risk of 90-day major complications was associated with two female (11.0-12.4 [RR: 1.52; p < 0.001], 5.0-10.9 [RR: 3.40; p < 0.001]) and one male stratum (5.0-11.9 [RR: 2.02; p < 0.001]). Increased risk of 2-year deep infection was associated with one female (5.0-10.9 [RR: 3.67; p < 0.001]) and one male stratum (5.0-11.9 [RR: 2.11; p = 0.005]).

CONCLUSIONS:
SSLR analysis established single-level lumbar fusion-specific hemoglobin strata that maximize the likelihood of 90-day blood transfusions and predict the risk of 90-day major complication and 2-year deep infection. We recommend using these thresholds during preoperative optimization, noting the sequential increase in risk of complications starting with a hemoglobin of less than 13.5 in males and 12.5 in females.
511 Iron Oxide Nanoplatform HMC-FMX for Targeted Chemotherapeutic Treatment of Glioblastoma
Authors: Mohyeddinipour Sarah , Israel Liron , Miyaguchi Ken , Wang Hongqiang , Michel Michelot , Tusa Lavieri Miguel Eduardo , Rajiv Subashni , Watanabe Junji , Yu John S. 
Published: March 2024

INTRODUCTION:
Glioblastoma multiforme (GBM), is the most common and aggressive form of primary brain tumors in adults with a high mortality rate. Despite the emergence of potent chemotherapies, clinical efficacy has been limited in part due to the blood-brain barrier (BBB). Therefore, recurrence rate is high, limiting life expectancy. Our nanoplatform is based on ferumoxytol (FMX), an FDA-approved MRI-sensitive supramagnetic iron oxide nanoparticle conjugated to heptamethine cyanine (HMC), a near infrared-flourescent ligand that specifically targets organic anion transporter polypeptides (OATP) expressed in GBM and endothelial cells.

METHODS:
To show the specificity of OATP-targeting by HMC-FMX nanoplatform, cells were pre-incubated with OATP inhibitors and then incubated with HMC-FMX. Fluorescent intensity and HMC uptake were assesed by flow cytometry. Cytotoxicity of the drug-loaded nanoparticles, HMC-FMX(SN38) and HMC-FMX(CPT) compared to SN38 and Camptothecin (CPT) in U87 cells was assessed by flow cytometry following cell staining with Annexin and 7-AAD.

RESULTS:
The HMC-FMX nanoplatform is successfully taken up by both U87 and endothelial cells. OATP inhibition significantly decreased HMC uptake (10%-30%) in comparison to control in U87 and endothelial cells. In addition, HMC-FMX(SN38) and HMC-FMX(CPT) exerted increased cytotoxic effect on U87 cells compared with SN38 and CPT alone. Furthermore, majority of apoptotic cells were observed in the HMC-positive cells in contrast to HMC-negative cells.

CONCLUSIONS:
HMC-FMX can encapsulate chemotherapeutic drugs, such as SN38 and CPT. HMC-FMX as a nanoplatform demonstrates specific, safe and efficient drug delivery through the BBB into GBM cells in vitro.