bluuebunny/crossref_metadata_2025_split huggingface dataset:
351 Claudin 6 Expression in Atypical Teratoid/Rhabdoid Tumors is a Target for CAR-T Cell Therapy
Authors: Madsen Peter J. , Stern Allison , Griffin Crystal , Oehm Petr , Rengstl Benjamin , Flemmig Carina , Tucker Alexander , Storm Phillip B. , Resnick Adam C. , Foster Jessica 
Published: March 2023

INTRODUCTION:
Novel therapies for atypical teratoid/rhabdoid tumor (ATRT) are desperately needed. Claudin-6 (CLDN6) is a tight junction protein present during early development and in some tumors, but not at appreciable levels in normal tissue. CLDN6-targeted chimeric antigen receptor (CAR) T cells with a CAR-T cell–amplifying RNA vaccine have demonstrated antitumor activity against CLDN6-expressing cancers in pre-clinical and clinical trials (NCT04503278; Haanen J et al AACR, 2022).

METHODS:
CLDN6 expression was assessed on primary ATRT specimens by RNAseq and immunohistochemistry and on tumor-derived cell lines by flow cytometry. CLDN6-positive and negative cell lines were co-cultured with CLDN6-targeting CAR-T cells and killing efficacy was measured. A second-generation mRNA CAR with a 4-1BB costimulatory domain and single-chain variable fragment directed against CLDN6 was used (Reinhard et al, 2020). Cell lines were modified with reporter assays and intracranial xenografts were created in NSG mice.

RESULTS:
50% of specimens had CLDN6 expression greater than 2 FPKM (N = 28). Immunohistochemistry was positive in 53% of specimens (N = 15). Multiple CLDN6-positive ATRT cell lines were identified by flow cytometry. Co-culture of CLDN6-directed mRNA CAR-T cells with ATRT line 7316-2187 resulted in tumor-specific cytotoxicity versus CD19-directed control CAR-T cells (92% versus 15% at 10:1, p < 0.0001; 86% versus 0% at 5:1, p < 0.0001). Similar results were seen with an additional CLDN6-positive ATRT cell line 7316-2141 (75% versus 7% at 10:1, p < 0.0001; 53% versus 0% at 5:1, p < 0.0001). Both CLDN6- and CD19-directed CAR-T cells showed no cytotoxicity against a CLDN6-negative cell line, 7316-4149. Xenografts were successfully created, and ongoing work is evaluating locoregional administration of CLDN6-directed CAR-T cells.

CONCLUSIONS:
This work highlights the potential of targeting CLDN6 with CAR-T cell therapy as a novel treatment strategy for patients with ATRT.
353 Cerebellar Tonsil Reduction for Surgical Treatment of Chiari I Malformation in Children
Authors: Montgomery Eric , Swift Dale , Pernik Mark Nicholas , Whittemore Brett A. , Weprin Bradley , Price Angela V. , de Oliveira Sillero Rafael , Braga Bruno 
Published: March 2023

INTRODUCTION:
There remains much debate around ideal surgical technique for Chiari Malformation Type 1. Although recent trends favor less invasive techniques, growing evidence may support tonsillar reduction via resection or coagulation.

METHODS:
We retrospectively reviewed 456 consecutive children (<18 years of age) surgically treated for Chiari I malformation. Procedures were classified into four groups: bone decompression (PFD) and duraplasty (PFDD), PFDD with arachnoid dissection (PFDD + AD), PFDD with coagulation of at least one cerebellar tonsil (PFDD + TC) and PFDD with subpial resection of at least one tonsil (PFDD + TR).

RESULTS:
Preoperatively, univariate analysis showed that brainstem/spinal cord symptoms, use of cine MRI, tonsil length, and distance from the opisthion to brainstem were correlated with the surgical technique used. Multivariate analysis demonstrated that only tonsil length was independently associated with surgical technique choice: it was directly associated with utilization of PFDD + TR over PFDD (p = 0.001) or PFDD + AD (p = 0.005) and with PFDD + TC over PFDD (p = 0.005). Postoperatively, symptoms improved in 56/71 (78.9%) of patients in the PFDD group, 23/26 (88.5%) in PFDD + AD, 77/92 (83.7%) in PFDD + TC and 235/267 (88.0%) in PFDD + TR. Syringomyelia improved greater than 50% in 80.4% of patients in PFDD + TC/TR versus only 58.8% of PFDD + D/AD (p = 0.001). Reoperation rates and postoperative headaches were decreased (3.1% and 14.5%, respectively) in the PFDD + TC/TR group compared to the PFDD + D/AD group (8.3% and 25.8%, respectively), and they were both statistically significant (p-value = 0.023 and 0.008, respectively). Postoperative complication rates were not statistically different between the groups.

CONCLUSIONS:
In this single center retrospective series, cerebellar tonsil reduction, by either coagulation or sub-pial resection, results in superior reduction of syringomyelia in Chiari I patients with less reoperations and without increased complications.
356 Intraoperative Robotic Planning Software is Accurate at Predicting Postoperative Lumbar Lordosis After Anterior Column Reconstruction
Authors: Shah Vaibhavi , Haider Ghani , Stienen Martin N. , Veeravagu Anand 
Published: March 2023

INTRODUCTION:
Re-establishment of lumbar lordosis with spine deformity surgery is considered a pre-requisite for long term positive results with less biomechanical loading on the adjacent segments, reducing the likelihood of developing adjacent segment disease. The pre-operative planning softwares of robotic systems now allow the surgeon to plan a patient-specific surgical plan and are also able to predict the degree of lumbar lordosis following the instrumentation surgery based on pre-operative imaging by using vertebral segmentation.

METHODS:
We conducted a retrospective review of patients aged 18 or older who underwent pedicle screw spinal instrumentation using the Mazor X Robot (Medtronic Inc., Minneapolis, MN, USA), performed by one surgeon over a five-year period. The robotic guidance software (Mazor X-Align, Medtronic Inc., Minneapolis, MN, USA) was used to calculate the predicted lumbar lordosis based on pre-operative imaging. Wilcoxon Rank test was used to compare the predicted angles to the observed lumbar lordosis on post-operative radiographs.

RESULTS:
A total of 15 patients (46.6% female) with a mean age of 61.5 ± 10.9 years were identified, who underwent posterior lumbo-sacral spinal fusion with the robotic system using both percutaneous and open approach. Instrumentation was done across a mean of 3.27 levels per case and 11 patients (73.3%) underwent anterior column reconstruction prior to posterior fixation without the need for an intra-operative CT spin. There was no statistical difference between the predicted and the actual post-operative lumbar lordosis (p-value: 0.334) while there was a significant statistical difference between the pre-operative and post-operative angles (p-value: 0.02).

CONCLUSIONS:
Our study suggests that the intraoperative robotic planning software of the Mazor X system is accurate at predicting postoperative lumbar lordosis which can be useful and help guide surgical decision making and planning.
360 Assessment of Pedicle Screw Placement Accuracy Utilizing a Novel Augmented Reality and Artificial Intelligence Surgical Guidance System
Authors: Luciano Cristian , Cornwall Bryan , Malone Hani , St. Clair Selvon , Parfeniuk Katya , Trzmiel Michal , Siemionow Krzysztof 
Published: March 2023

INTRODUCTION:
The integration of artificial intelligence (AI) and augmented reality (AR) technologies in spine navigation has the potential to minimize pedicle screw misplacement, decrease radiation exposure, and improve procedural efficiency, addressing some of the challenges associated with spinal instrumentation.

METHODS:
Sixty lumbosacral pedicle screws were placed by 4 Orthopedics surgeons in 6 cadavers using the AR/AI surgical navigation system. Two CT intraoperative scans (before and after screw placement) of the cadaveric specimens were obtained for the study to measure the 3D positional and angular discrepancies between virtual and real screws. The validation procedure consisted of 3 steps: (1) automatic registration and 3D coordinate transformation, where the preop CT scan was aligned with the postop scan to determine the virtual screw 3D positions and orientations in postop scan; (2) analysis of the postop scan to determine the real screw 3D positions and orientations as they appeared in the scan volume; (3) automatic comparison between the 3D positions and orientations of the virtual and real screws.

RESULTS:
A one-sample t-test statistical analysis yielded a mean positional error of 2.16 mm ± 1.00 mm (99% CI: 1.81-2.49 mm), and a mean angular error of 1.49± 0.73° (99% CI: 1.25-1.74°). These results were independent of anatomical level, side, and surgeon.

CONCLUSIONS:
This study indicates that this AR/AI surgical guidance system provides mean positional and angular errors lower than 3.0 mm and 3.0° respectively, thus complying with FDA-required regulatory acceptance criteria. The system was FDA-cleared as a US 510k Orthopedic Stereotaxic Instrument.
376 From Core to Margin: Intratumoral Differences in Cancer Hallmarks Depend on Spatial Localization of Cells in Glioblastoma
Authors: Suarez-Meade Paola , Figueredo Luisa F. , Roberts Mckinley , Brooks Mieu , Zarco Natanael , Guerrero-Cazares Hugo , Chaichana Kaisorn L. , Schiapparelli Paula , Quinones-Hinojosa Alfredo 
Published: March 2023

INTRODUCTION:
Glioblastoma (GBM) carries a dismal prognosis due to its invasive nature. Studies show that GBMs have transcriptionally heterogeneous cell populations within the same tumor. However, information regarding the biological behavior of different intratumoral populations has never been demonstrated in vitro.

METHODS:
GBM patients who underwent resective surgery were consented for research. MRI-guided images were registered during resection to localize the area where samples were obtained. Two GBM cell lines were established from the same patient for each case: margin and core cell line. Proliferation, migration, and stemness experiments were performed in vitro and intracranial implantation of tumors was then carried out to evaluate tumor behavior in vivo.

RESULTS:
10 cell lines from 5 patients were established from the margin and the core. There were no differences in cell proliferation. Sphere area and limiting dilution assay (p < 0.01) show that cells derived from the margin have greater stemness capabilities. Cells from the margin have higher migratory abilities in transwell migration assay (p < 0.01 in 4/5 patients) and in real-time cell invasion monitoring (p < 0.01). Trend which was later noted in sphere invasion assay. In vivo studies demonstrate that both cell populations were capable of tumor engraftment with no differences in tumor growth by bioluminescence (p > 0.05). Nonetheless, tumors from the marginal area demonstrated a more diffuse phenotype and greater extension when compared core-derived tumors on histopathology .

CONCLUSIONS:
There is a large degree of behavioral heterogeneity between cells from the tumor core versus the margin. GBM cells from the margin have higher migration and stemness properties when compared to their core counterparts in vitro; suggesting that peripheral cells carry more aggressive phenotypes that could be responsible for treatment resistance and tumor recurrence
408 Racial Disparities in Long-Term Functional Outcome After Traumatic Brain Injury: An Update
Authors: Bah Momodou , Eden Sonia Veronica , Chen Alex , Simo Leticia , Tummala Shalini , Mahas Rachel 
Published: March 2023

INTRODUCTION:
Racial disparities in outcomes have been reported in various medical conditions and in patients with traumatic brain injury (TBI). Despite equal access to acute rehabilitation, blacks had significantly worse long-term functional outcomes after TBI than non-Hispanic whites (NHWs). Much effort has been placed on raising awareness, improving access to care, expanding research, and on closing racial disparity gaps in healthcare.

METHODS:
Patients followed and tracked in the Southeastern Michigan Traumatic Brain Injury System (SEMTBIS) database were inquired, including 95 non-Hispanic whites (NHWs) and 97 blacks. Severe TBI was defined as Abbreviated Injury Scale [AIS] score of 3–5. Patients from February 2010 to December 2019 were included. Long-term outcomes were measured by 1) the percentage of patients discharged to home, and 2) the Glasgow Outcome Scale-Extended (GOSE) score after 1 year. Student’s T-test was used for numeric data analysis. Chi-square was used for categorical data comparison.

RESULTS:
There were no significant differences in initial TBI severity between non-Hispanic whites (NHWs) and blacks, measured by the admission Glasgow Coma Scale (GCS), the percentage of people who had midline shift >5 mm on brain CT, the number of days from injury to date out of posttraumatic amnesia, and of days from injury to following commands. More NHWs were discharged to low acuity facilities (80% versus 58.8%, P = 0.0014). A higher percentage of NHWs had an upper good recovery score, which is a GOSE score of 8 (23.1% versus 9.3%, P = 0.074) after 1-year follow-up.

CONCLUSIONS:
Despite efforts to mitigate racial disparities in medical outcomes after TBI, the blacks in Southeastern Michigan continue to score lower than NHWs on their long-term functional outcomes at one-year follow-up.
419 Integration of Trainees with Mobility Impairment in Neurological Surgery
Authors: Lawrence Jesse D. , Konrad Peter , Sedney Cara L. 
Published: March 2023

INTRODUCTION:
Increasing attention has been paid to diversity amongst neurosurgical trainees in recent years; but representation of individuals with mobility impairment within neurosurgical training has not been previously demonstrated.

METHODS:
A trainee with mobility impairment (JL) matriculated to neurosurgical residency in 2017 with programmatic and institutional support. Prior to matriculation he had independently developed standing wheelchairs and operating room protocols. Upon matriculation, a careful needs assessment was performed with the assistance of JL and the university ADA officer and accommodation recommendations were provided. These consisted of generally minor procedural or equipment alterations, including hand controls for surgical devices, cord covering mats in the operating rooms, minor changes to scrub stations and call room, parking access, etc. Minor iterative technique guidance was provided with respect to body mechanics and adaptive equipment which was not demonstrably different than that provided to other residents (eg left hand dominant residents).

RESULTS:
The trainee has successfully performed in all roles of neurosurgical residency, including the chief resident role, with no alteration of duties, expectations, or assignments. In regards to adaptive equipment, no one solution could be considered ideal for all situations. Specifically, operating room adaptations needed to optimize positioning and mobility while bedside adaptations needed to optimize ease of access and low profile.

CONCLUSIONS:
Integration and training of individuals with mobility impairment can be successful with minor procedural and equipment alterations, even in a small program with relatively limited resources. This experience demonstrates feasibility and provides a blueprint for other institutions and applicants with mobility impairment who desire to pursue neurosurgical training.
423 Trends in Utilization of Standardized Letters of Recommendation in the 2021-2022 Neurosurgery Application Process
Authors: Feldman Michael , Ortiz Alex , Roth Steven G. , Dambrino Robert J. , Yengo-Kahn Aaron Michael , Chitale Rohan V. , Chambless Lola Blackwell 
Published: March 2023

INTRODUCTION:
Standardized LORs (SLORs) were introduced during the 2020-2021 neurosurgery residency application cycle, but suffered from poor inter-rater reliability and significant grade inflation. Changes were made to the SLOR template and utilization patterns in response to these shortcomings.

METHODS:
This cross-sectional study analyzed all SLORs submitted to a single neurosurgery residency program over the 2021-2022 cycle. Data from seven competency domains and the overall rating were recorded and stratified by academic category of letter writer. Inter-rater reliability was evaluated using Krippendorff’s Alpha. Frequency of letters written was evaluated using Kruskal-Wallis H Test.

RESULTS:
90% of SLORs rated applicants among the Top 25%, but there was a significant decrease in the usage of the “Top 1%” and “Top 2-5%” ratings from the prior application cycle. Inter-rater reliability was poor across all competencies. Writers who completed one SLOR rated applicants higher and had a narrower range than those who completed multiple SLORs.

CONCLUSIONS:
Changes in the format and subsequent utilization patterns of SLORs have slightly decreased grade inflation; however, inter-rater reliability remains poor. The most wide-ranging evaluators submitted the highest number of SLORs, suggesting that future evaluation and usage of SLORs should emphasize letter-writer characteristics and numbers of SLORs written. Overall, SLORs have been well and broadly accepted with subtle improvements in the second year of utilization.
425 Intraoperative Surveillance of the Vertebral Artery Using Indocyanine Green Angiography and Doppler Sonography in Craniovertebral Junction Surgeries
Authors: Lee Dong Hoon 
Published: March 2023

INTRODUCTION:
The surgical approach for craniovertebral junction (CVJ) procedures may be complicated for many reasons due to sensitive relationships involved in the surrounding neurovascular structures and complex biomechanical issues.

METHODS:
In total, 344 consecutive patients enrolled who underwent CVJ surgery. Surgery was performed without intraoperative VA monitoring tools in 262 cases (control group) and with VA monitoring tools in 82 cases (monitoring group). The authors compared the incidence of VAI between groups. The procedure times of ICG angiography, change of VA flow velocity measured by Doppler sonography, and complication were investigated.

RESULTS:
There were 4 VAI cases in the control group, and the incidence of VAI was 1.5%. Meanwhile, there were no VAI cases in the monitoring group. The procedure time of ICG angiography was less than 5 minutes (mean [±SD] 4.6 ± 2.1 minutes) and VA flow velocity was 11.2 ± 4.5 cm/sec. The combined use of ICG angiography and Doppler sonography was useful not only to monitor VA patency but also to assess the quality of blood flow during CVJ surgery, especially in the high-risk group of patients.

CONCLUSIONS:
The combined use of ICG angiography and Doppler sonography enables real-time intraoperative monitoring of the VA by detecting blood flow and flow velocity. As the arteries get closer, they provide auditory and visual feedback to the surgeon. This real-time image guidance could be a useful tool, especially for high-risk patients and inexperienced surgeons, to avoid iatrogenic VAI during any CVJ surgery.
439 Percutaneous Electrical Nerve Stimulator for Treatment of Chronic Spinal Pain
Authors: Bindal Shriya , Bindal Maya , Lall Maureen 
Published: March 2023

INTRODUCTION:
The percutaneous electrical nerve stimulator (PENS) is a relatively new device for the treatment of chronic spinal pain. This programmable device is worn for a recommended 10 to 12 days on the external ear, stimulating the auricular vagus nerve. It is postulated to release endorphins and relieve pain. There is minimal literature on the use of PENS as an adjunct to pain management in patients with chronic spinal pain.

METHODS:
Patients who had the PENS placed for chronic refractory spinal pain were included in the study. All patients failed multiple forms of treatment such as physical therapy, epidural steroid injections, and medication.

RESULTS:
In 2021, 114 patients had the PENS placed. The mean patient follow-up was 34.9 weeks. 67 patients (58.7%) felt pain relief due to the PENS. In patients with neck pain, the mean Neck Disability Index scores decreased from 43.8% to 25.4%, and the mean Numerical Rating Scores (NRS) decreased from 7.9 to 3.9. In patients with low back pain, the mean Oswestry Disability Index scores decreased from 47.6% to 33.5%, and the mean NRS scores decreased from 7.9 to 5.1. The rate of improvement in patients with neck pain (71.9%) was significantly greater (p-value <0.02) than in patients with back pain (56.4%). Interestingly, 33.3% of patients who responded to treatment remained improved at one year follow-up.

CONCLUSIONS:
Our study shows that a significant number of patients experienced reduced pain and disability as a result of treatment with the PENS. Patients with neck pain responded better than patients with low back pain. Many patients in this difficult patient population experienced durable relief, lasting over one year. Our study suggests that the PENS may be a useful adjunct in the management of patients with chronic spinal pain.
450 A Shared Cortical Language Network for Multimodal Naming
Authors: Snyder Kathryn , Forseth Kiefer , Tandon Nitin 
Published: March 2023

INTRODUCTION:
Surgical resections for epilepsy or neoplasms often result in naming deficits. While various brain regions are hypothesized to support separable processes, the language network and its functional mapping to naming remain unclear. However, such knowledge could improve the localization of critical brain regions to preserve language function.

METHODS:
Data were obtained from epilepsy patients who underwent invasive electrophysiology. Recordings were acquired during three cued-naming tasks using pictures (n = 120), auditory descriptions (n = 82), and orthographic descriptions (n = 68). High-gamma power (65-115Hz) was used to measure activity, and group-level activity was estimated using surface-based mixed-effects multilevel analysis.

RESULTS:
Analyses showed left-lateralized heteromodal activity in the inferior frontal gyrus (IFG), the middle fusiform gyrus (mFus), and the intraparietal sulcus (IPS) following sensory processing. Activation of mFus peaked 150ms before stimulus offset for auditory (15.2%, p < 10-6) and orthographic (21.4%, p < 10-6) naming and 350ms after picture onset (39.0%, p < 10-6) for visual naming. IPS activation peaked just before stimulus offset for auditory (38.1%, p = 7.7*10-5) and orthographic (27.5%, p = 0.008) naming and 450ms following picture onset (43.0%, p < 10-6) for visual naming. IFG activation peaked just before stimulus offset for auditory (30.1%, p < 10-6) and orthographic (40.1%, p = 10-6) naming and 500ms after picture onset (36.4%, p < 10-6) for visual naming. The left posterior middle temporal gyrus (pMTG) showed heteromodal activity for auditory and orthographic but not visual stimuli with peak activation occurring before convergence of all tasks 250ms before stimulus offset (auditory = 34.1%, p < 10-6;orthographic = 25.5%, p = 0.0035).

CONCLUSIONS:
These results reveal a heteromodal network of IFG, mFus, and IPS supporting lexical access. Our findings also implicate the role of pMTG in phonological access. Altogether, this work characterizes the roles of key regions within language networks, which could influence surgical approaches to minimize postoperative language deficits.