bluuebunny/crossref_metadata_2025 huggingface dataset:
213 Acute Flow Diversion for Ruptured Cerebral Aneurysms Arising From Vessels of Small Caliber Using FRED Jr: A Clinical Case Series
Authors: Doron Omer , McLellan Rachel , Vranic Justin , Regenhardt Robert , Stapleton Christopher James , Patel Aman B.
Published: March 2024

INTRODUCTION:

Ruptured aneurysms arising from small caliber (<2.5 mm) or distal vessels beyond the circle of Willis are considered challenging for all treatment modalities. Recently, the FRED Jr stent, designed for flow diversion in small arteries, was approved in the US for the treatment of non-ruptured aneurysms.

METHODS:

Clinical and radiological records of patients sustaining SAH treated with FRED Jr between June 2020 and October 2022 were reviewed. Treatment course including anti-platelet therapy, external ventricular drain (EVD) management, and vasospasm, as well as clinical outcomes were analyzed. Angiographic results were assessed according to the O’Kelly-Marotta (OKM) scale.

RESULTS:

Nine patients with at a median age of 62 (27-75) were included. The median Hunt Hess score was 2 (IQR 1) and modified Fischer score was 4 (IQR 1). Six aAneurysms’ morphologies included were saccular (6 case), 1 blister (1 case) and 2 were and dissecting (2 cases) type, located at the ACOM complex (3), A2/A3 (3), M2/M3 (1), V4 (1), and P2 (1) segments. All stents were deployed successfully with no intraprocedural complications. Post-operatively, no re-bleeding events were encountered. Vasospasm therapy was initiated in 6 cases, and no symptomatic EVD-related hematomas were observed. Post- operative ischemic events were encountered in 2 cases. Median 3-month mRS was 2 (IQR 1) for the7 surviving patients, and 3-months radiographic follow-up revealed OKM scale D in 4/7 cases.

CONCLUSIONS:

Flow diversion as a potential treatment strategy for acutely ruptured aneurysms arising from small caliber vessels is feasible using FRED Jr. Since As the complication profile reported in this series is comparable to historical microsurgical cohorts and effective protection was conferred by this treatment modality, our small cohort provides a glimpse into acute flow diversion for this subset of difficult-to-treat aneurysms.
218 Cost-Effectiveness and Quality-Adjusted Life Years Analysis for Endovascular Management of Acute Stroke With a Large Ischemic Region
Authors: Adeeb Nimer
Published: March 2024

INTRODUCTION:

Mechanical thrombectomy (MT) for acute ischemic stroke is generally avoided when the infarction is large (defined as ASPECT score of < 5). However, a recent trial (RESCUE-Japan) published in NEJM, showed that patients with large cerebral infarctions had better functional outcomes, measured as mRS of 0-3 at 90 days, with MT compared to best medical management (BMM) alone.

METHODS:

Treeage, a decision-analytic software, was used to construct a cost effectiveness analysis model that compares the cost-effectiveness of MT vs. BMM alone based on the RESCUE-Japan study. The model includes a short-term decision model that examines costs and clinical outcomes of patients with acute ischemic stroke during the initial three months of treatment. Additionally, a long-term Markov state transition model is created to estimate expected outcomes and costs annually over a 20-year timeframe, with patients potentially experiencing recurrent strokes, transitioning to lower health states, and death from stroke. The success of each treatment was evaluated using QALYs. Then, to assess the robustness of this model, a sensitivity analysis was performed.

RESULTS:

In the base–case analysis of the total study population using a time horizon of 20 years, MT and BMM alone were found to have a 2.86 QALY and 1.44 QALY, respectively. This increase in the number of QALY by MT came at a lower cost of $275,805 compared to BMM alone, which had a cost $282,476. The incremental cost-effectiveness ratio (ICER) was determined at $-4697/QALY. The results were further supported by the 1-way deterministic and probabilistic sensitivity analyses.

CONCLUSIONS:

This study shows that, besides having a better clinical outcome, MT was more cost effective and associated with higher QALYs compared to BMM alone, when accounting for health care cost associated with treatment outcome.
231 Postoperative Seizure Outcome of a Cohort of Patients With Drug Resistant Epilepsy and Malformations of Cortical Development Selected Predominantly by Non-invasive Evaluation
Authors: Malla Bhaskara Rao , Rewatkar Ajinkya , Arimappamagan Arivazhagan , Sinha Sanjib
Published: March 2024

INTRODUCTION:

Optimizing the surgical outcome of people with drug-resistant epilepsy (DRE) and malformations of cortical development (MCD) can be quite challenging. The studies are limited in this regard, especially from the low and middle income countries (LAMIC).

METHODS:

Between April, 2011 and March, 2023, 584 people with drug resistant epilepsy underwent surgery at NIMHANS, Bangalore, India. MCD as an underlying substrate have been identified among 170 patients. Different types of MCD, their pre-surgical evaluation, surgical strategy and outcome predictors have been studied.

RESULTS:

Cohort consists of 170 people with a mean age at surgery of 17.01 ± 10.94 (range 1.2 – 60) years. Mean age at seizure onset of 7.45 ± 7.39 (range 1 month to 40) years. The mean duration of epilepsy before surgery of 9.17 ± 7.58 (range 1-32) years. Males constituted 62.35% of patients (n= 106). Mean seizure score of the cohort was at 8.61 ± 1.34 (range 4-12 on a scale of 0 -12). Lifetime drugs tried by the cohort ranged from 1- 6 with mean of 2.85 ± 0.95. FCD was noted in 120 patients (70.587%). At a mean follow up of 4.66 ± 2.80 years, cohort had an Engel outcome class Ia, I, II, III and IV of 71.1%, 83.6%, 3.1%, 7.80% and 5.5 % respectively. Range of current AEDs used by the cohort is nil to 5, with mean of 2.28 ± 1.41.

CONCLUSIONS:

In this study, three variables were found to influence the outcome towards favourable arm of Engel class Ia. These factors are histopathology of FCD with balloon cells, glioneuronal aetiology and an age of less than 18 years at the time of surgery.
232 Onco-functional Outcome After Resection for Eloquent Glioblastoma (GLIOFO): A Propensity-score Matched Analysis of an International, Multicenter, Cohort Study
Authors: Gerritsen Jasper , Mekary Rania , Pisica Dana , Zwarthoed Rosa , Kilgallon John , Lee Ahmad Nawabi Noah , Jessurun Charissa , Versyck Georges , Pruijn Koen , Fisher Fleur , Larivière Emma , Solie Lien , Kloet Alfred , Tewarie Rishi Nandoe , Schouten Joost , Bos Eelke , Smith Timothy R. , Dirven Clemens M. F. , Broekman Marike , Vincent Arnaud , De Vleeschouwer Steven
Published: March 2024

INTRODUCTION:

Minimizing residual tumor volume and preventing functional loss are the primary goal in glioblastoma resections in eloquent areas. However, their combined impact on patient outcomes remains poorly understood.

METHODS:

Propensity-score matching was used to match OFO 1 (gross-total resection with no functional loss), OFO 2 (no gross-total resection with no functional loss), OFO 3 (gross-total resection with functional loss) and OFO 4 patients (no gross-total resection with functional loss) for the overall cohort and subgroups. Cox proportional-hazard regressions were performed to analyze the association between OFO class and surgical outcomes. Logistic regressions were performed to identify preoperative predictors for OFO class.

RESULTS:

Between 2010 and 2020, 858 patients were included as the overall unmatched cohort. After matching, the cohort comprised of 512 patients: 256 received OFO 1 and 256 received non-OFO 1. OFO 1 resulted in fewer postoperative neurological deficits at 6 weeks (10.2% vs. 25.8%, p < 0.001), 3 months (12.7% vs. 9.9%, p < 0.001), and 6 months (21.0% vs. 35.1%, p = 0.0010); lower rates of KPS deterioration at 3 months (14.2% vs. 52.4%, p < 0.001), and 6 months (26.5% vs. 52.9%, p < 0.001); higher rate of receipt of adjuvant therapy (HR 3.91, p < 0.001), longer overall survival (median 21.0 vs. 13.0 months, p < 0.001), and longer progression-free survival (median 10.0 vs. 7.5 months, p < 0.001). Patients who underwent awake craniotomy more often received OFO 1 (43.0% vs. 26.9%, p < 0.001; OR 1.92, p = 0.0070).

CONCLUSIONS:

OFO 1 is beneficial in patients with eloquent glioblastoma to improve outcomes - irrespective of age, preoperative NIHSS, or KPS - in terms of survival, functional outcomes, and receipt of adjuvant therapy. Awake craniotomy was significantly associated with achieving this.
240 Impact of a Large Geographical Area on Outcomes in Acute Traumatic Intracranial Extra-axial Haemorrhage Requiring Urgent Surgical Evacuatio
Authors: Mantha Sidharth , Olson Sarah
Published: March 2024

INTRODUCTION:

The Princess Alexandra Hospital (PAH) Department of Neurosurgery services a population of 1.85 million people over a 420,000 km2 area in Queensland, Australia. Increased distance from a neurosurgical centre has previously been correlated with poorer outcomes in traumatic brain injury.

METHODS:

This single-centre retrospective study identified patients aged 16-85 who underwent evacuation of an acute traumatic subdural (ASDH) or extradural haemorrhage (EDH) between 2016 and 2022. Initial Glasgow Coma Score (GCS), pupillary abnormalities, time to intervention, distance from PAH and the Extended Glasgow Outcome Scale (GOS-E) at 6 months were recorded.

RESULTS:

106 and 50 patients underwent evacuation of ASDH and EDH respectively. In the ASDH group, age was inversely correlated (p = 0.03, r2 = 0.04) and the motor component of the initial GCS was directly correlated (p = 0.002, r2 = 0.09) with GOS-E at 6 months. Distance from PAH directly correlated with an increased time to intervention (p<0.0001, r2 = 0.23) but did not correlate with GOS-E at 6 months (p = 0.09). There was no difference between survivors and non-survivors regarding distance from PAH (43.43 ± 75.05 km vs. 25.56 ± 41.32 km, p = 0.15) or time to operation (276.14 ± 192.77 mins vs. 217.40 ± 147.27 mins, p = 0.08). This was also found for survivors with poor (GOS-E <6) and fair (GOS-E = 6) recovery at 6 months. In the EDH group there was no correlation between distance, time to operative intervention, age or initial motor score with outcomes at 6 months.

CONCLUSIONS:

Whilst increased distance from treatment centre correlated with increased time to surgical intervention for ASDH, it did not impact on survival or functional outcomes at 6 months. For ASDH requiring urgent evacuation, increasing age and severity of primary brain injury are predictors of poorer long-term outcomes.
260 Pediatric Penetrating Head Trauma: Do Children Need to be Taken to Pediatric Trauma Centers?
Authors: Wathen Connor , Howard Susanna , Kaufman Elinore , Cannon Jeremy , Petrov Dmitriy , Schuster James M.
Published: March 2024

INTRODUCTION:

Gun violence has become the leading cause of death in children. Debate exists regarding the optimal treatment setting for pediatric trauma patients at either Adult Trauma Centers (ATC) or Pediatric Trauma Centers (PTC).

METHODS:

A retrospective analysis of the National Trauma Data Bank (NTDB) was performed from 2017-2020. Inclusion criteria included age 18 years or younger, firearm related mechanism, and associated ICD-10 code corresponding to intracranial injury. Patient characteristics and outcomes were compared across groups.

RESULTS:

2,662 cases met inclusion criteria. Overall mortality was 52.1%. 57.4% of patients presented to ATC, 12.8% to PTC, and 29.7% to dual-certified centers. The median age of patients treated at ATC was 17, 13 at PTC, and 16 at dual-certified centers. While mortality was lower for patients presenting to PTC relative to ATC and dual-certified centers (38.2% vs. 55.6% vs. 52.9%, respectively, p < 0.001), PTC patients had higher GCS scores (7.8 vs. 6.5 vs. 6.7, p < 0.001) and lower rates of bilaterally fixed and dilated pupils at presentation (38.9% vs 53% vs 6.7%, p < 0.001). In a logistic regression analysis controlling for baseline pupillary response, GCS, age, ISS, and treatment center type, no significant association was seen between center type and mortality (p = 0.550).

CONCLUSIONS:

Although mortality was significantly higher for patients presenting to ATC, when baseline injury severity was controlled for, no statistically significant effect was seen with respect to mortality. These results show that the bulk of pediatric GSW are already being treated at ATC and suggest that there is no significant difference in mortality relative to PTC.
269 Risk Factors for Fusion Failure in Children Undergoing Occipital to C2 Rigid Instrumentation and Fusion
Authors: Eremiev Alexander , Kurland David B. , Cheung Alexander , Dastagirzada Yosef Michael , Harter David H. , Rodriguez-Olaverri Juan , Brockmeyer Douglas L. , Pahys Joshua , Hedequist Daniel J. , Oetgen Matthew , Anderson Richard C.E.
Published: March 2024

INTRODUCTION:

Studies of pediatric occipital-cervical fusions have been limited, and there is substantial variation among surgical constructs with reported failure rates as high as 20%.

METHODS:

The Pediatric Spine Study Group (PSSG) registry was queried to identify patients </= 21-years-old who had: (1) O-C2 posterior rigid instrumentation and fusion, (2) 2-year clinical and radiographic follow-up, and (3) available post-operative lateral cervical radiograph or CT. Failure was defined as hardware revision surgery >30 days following the index procedure or the presence of screw haloing or breakage on the most recent imaging study. Univariate comparisons were made using Mann-Whitney U-tests, Chi-square tests, and Fisher’s Exact tests followed by multivariable logistic regression.

RESULTS:

76 patients were included. The median age at surgery was 9 years (range, 0.2 to 17.2 years), and 51% of the cohort was male. 55% percent of patients had syndromic etiology (41/75), and the most frequent diagnosis was Down Syndrome (28%). Of the 74 patients with complete information, 28/74 (38%) had fusion failure (95% CI, 27%-50%). Rib autographs were used more frequently in patients with successful fusions compared to failures (52% vs 25%; p = 0.04). Multivariable logistic regression determined that patients with rib autograft have a 75% decrease in the odds of failure compared to those without rib autograft (OR = 0.25; 95% CI = 0.08-0.75; p = 0.01). Other variables did not influence the risk for failure.

CONCLUSIONS:

In this multicenter, international registry study of children undergoing O-C2 rigid instrumentation, fusion failure was seen in 38% of patients, a higher rate than previously reported. Based on this study, the use of structural rib autograft should be considered to reduce fusion failure.
276 Outpatient Versus Inpatient Laminoplasty for Cervical Spondylosis: A Non-inferiority Analysis of Surgical Outcomes
Authors: Nathani Karim , Ghanem Marc , Ibrahim Sufyan , Ghaith Abdul Karim , Jarrah Ryan , Bydon Mohamad , Dominari Asimina
Published: March 2024

INTRODUCTION:

A rising trend of outpatient spinal procedures has been observed recently due to increasing evidence of lower risk of hospital-associated risks and better value-based healthcare delivery.

METHODS:

The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried for patients undergoing cervical laminoplasty for spinal spondylosis. Patients with a hospital stay of more than 48 hours were excluded from the comparative analysis to increase baseline comparability between the two groups. Patients undergoing other spinal procedures during the same hospital stay were also excluded. The outcomes of interest were postoperative complications, nonroutine discharge, readmissions, and reoperations within 30 days after surgery. The non-inferiority of outpatient compared with inpatient surgery was defined as a risk difference of <10.0% at a one-sided 97.5% confidence interval.

RESULTS:

A total of 808 cervical laminoplasty surgeries were identified. The study cohorts consisted of 107 and 701 patients in outpatient and inpatient groups, respectively. All recorded baseline characteristics, except age (58.3 ± 10.6 vs. 61.4 ± 11.5, p=0.01), were similar between the two groups. The incidences of postoperative complications were 2.8% and 3.4% for the outpatient and inpatient groups, respectively, while the non-routine discharge rates were 6.5% and 3.5%. Both groups had a 30-day readmission rate of 3.7%. In addition, the 30-day reoperation rates were 2.8 % and 1.4% for the outpatient and inpatient groups, respectively. Noninferiority of outpatient surgery was documented at a risk difference of 10% for postoperative complications, non-routine discharge, and readmission and reoperation rates.

CONCLUSIONS:

Outpatient cervical laminoplasty demonstrated similar early postoperative outcomes compared to inpatient surgery. Noninferiority in surgical outcomes after surgery was documented for outpatient compared with inpatient cervical laminoplasty surgery.
286 Bone Quality as Measured by Hounsfield Units More Accurately Predicts Proximal Junctional Kyphosis Than Vertebral Bone Quality Following Long-segment Thoracolumbar Fusion
Authors: Pennington Zach , Mikula Anthony L. , Lakomkin Nikita , Martini Michael Louis , Pinter Zachariah , Nassr Ahmad , Freedman Brett , Sebastian Arjun , Clarke Michelle J. , Krauss William E. , Bydon Mohamad , Fogelson Jeremy L. , Elder Benjamin D.
Published: March 2024

INTRODUCTION:

Both Hounsfield units (HU) on computed tomography and Vertebral Bone Quality (VBQ) score on MRI have been advanced as means of assessing underlying bone quality and predicting mechanical complications amongst spine patients.

METHODS:

Patients = 50 with =12-month follow-up following long-segment thoracolumbar fusion were included. Bone quality around the upper instrumented vertebrae (UIV) was measured using HU on preoperative CT and VBQ on preoperative MRI. Spinopelvic parameters were also measured. PJK was defined as a change of =10° in the Cobb angle between the cephalad endplate of UIV+2 and caudal endplate of UIV. Univariable analysis to identify predictors of the occurrence of PJK and survival analyses with Kaplan-Meier method and Cox regression were performed to identify predictors of time to PJK. Sensitivity analyses showed thresholds of HU < 164 and VBQ > 2.7 to be most predictive for PJK.

RESULTS:

Seventy-six patients (66.0 ± 7.0 yr; 27.6% male) were identified, with 15 suffering PJK. On univariable analyses PJK was predicted by high postoperative pelvic tilt (p = 0.038), postoperative T1-pelvic angle (p=0.041), and postoperative PI-LL mismatch (p = 0.028). On multivariable survival analysis, bone quality, as assessed by average HU of the UIV and UIV+1 was the only significant predictor of time to PJK (OR=3.053; 95%CI [1.032, 9.032]; p = 0.044). VBQ measured using the UIV, UIV+1, UIV+2, and UIV-1 vertebrae approached, but did not reach significance (2.913; [0.797, 10.646]; 0.106).

CONCLUSIONS:

In larger cohorts, VBQ may prove to be a significant predictor of PJK following long-segment thoracolumbar fusion. However, it has less predictive power than Hounsfield units on CT, suggesting preoperative workup for patients undergoing long-segment thoracolumbar fusion may benefit from CT versus MRI alone to identify those at increased risk of PJK.
287 What is the Velocity of Return-to-work After Circumferential Minimally-Invasive Surgery Versus Open Correction for Adult Spinal Deformity?
Authors: Macki Mohamed , Bess Shay , Uribe Juan S. , Mundis Gregory M. , Nunley Pierce D. , Le Vivian , Jamieson Alysha , Fu Kai-Ming G. , Wang Michael Y. , Anand Neel , Okonkwo David O. , Park Paul , Passias Peter G.
Published: March 2024

INTRODUCTION:

While faster recovery is a touted benefit of minimally-invasive spinal operations, these differences have been poorly described for return-to-work after larger fusion constructs for adult spinal deformity.

METHODS:

Adult spinal deformity (ASD) patients =18 yr were queried from a multicenter, prospective database across the USA. To ensure equal cohorts for comparing the impact of MIS vs. open correction technique, propensity score matched gender, age, BMI, pelvic incidence-lumbar lordosis mismatch, and sagittal vertical axis. Of 190 patients with baseline surveys, 173 respondents (91.0%) had both baseline employment and 2-year follow-up. The open and cMIS cohorts were compared with a chi-squared test. The rate of return-to-work was calculated via discrete-time proportional hazards model—reporting an adjusted odds ratio (ORadj)—at three follow-up intervals: 6 weeks, 1-year, and 2-years.

RESULTS:

Of 173 patients, baseline employment status was nearly equal between open (n = 85) vs cMIS (n = 88) cohorts: employed (20.0% vs 21.5%), unemployed (3.5% vs 4.5%), disabled (4.7% vs 6.8%), and retired (71.7% vs 67.0%) (p = 0.888). The number of employed patients between the open vs cMIS cohort statistically significantly differed at 1-year (10.5% vs 21.5%, p = 0.049), but not at 6 weeks (14.1% vs 15.9%, p = 0.741) or 2-years (14.1% vs 19.3%, p = 0.277). The velocity of return-to-work did not differ (OR = 1.2, p = 0.549). In a sub-analysis of 36 patients who were employed at baseline, the number of employed patients between the open vs cMIS cohort statistically significantly differed at 1-year (47.0% vs 89.4%, p = 0.006), but not at 6 weeks (70.5% vs 73.6%, p = 0.636) or 2-years (58.8% vs 78.9%, p = 0.191). The velocity of return-to-work was also similar (ORadj = 1.57, p = 0.481).

CONCLUSIONS:

Despite an equivalent baseline employment status, more patients in the cMIS cohort were employed at 1-year; however, there was no difference at 2-years. Similar trends were appreciated in a sub-analysis of patients who were employed at baseline.
294 Multi-omic Screening of Invasive GBM Cells in Engineered Biomaterials and Patient Biopsies Reveals Targetable Transsulfuration Pathway Alterations
Authors: Choudhary Nikita , Garcia Joseph , Akins Erin , Jain Saket , Wolf Kayla , Zhang Jason , Lad Meeki , Shukla Poojan , Gill Sabraj , Carette Luis , Zheng Allison , Kumar Sanjay , Aghi Manish Kumar
Published: March 2024

INTRODUCTION:

The poor prognosis of glioblastoma (GBM) is driven by tumor invasion; however, little is known of the metabolic alterations that drive invasion in glioblastoma.

METHODS:

We integrated spatially addressable hydrogel biomaterial platforms, patient site-directed biopsies, and multi-omics analyses to define metabolic drivers of invasive glioblastoma cells. A CRISPR metabolic gene screen was utilized to identify metabolic genes crucial for GBM invasion. We further targeted an identified hit from our high-throughput screens by utilizing a sgRNA to generate a knockdown cell line and assessing invasion in vitro and in vivo in a patient-derived xenograft orthotopic mouse model.

RESULTS:

Metabolomics and lipidomics revealed elevations in the redox buffers cystathionine, hexosylceramides, and glucosyl ceramides in the invasive front of both hydrogel-cultured tumors and patient site-directed biopsies, with immunofluorescence indicating elevated reactive oxygen species (ROS) markers in invasive cells. Transcriptomics confirmed upregulation of ROS-producing and response genes at the invasive front in both hydrogel models and patient tumors. Amongst oncologic ROS, hydrogen peroxide specifically promoted glioblastoma invasion in 3D hydrogel spheroid cultures. A CRISPR metabolic gene screen revealed cystathionine gamma lyase (CTH), an enzyme which converts cystathionine to the non-essential amino acid cysteine in the transsulfuration pathway, to be essential for glioblastoma invasion. Correspondingly, supplementing CTH knockdown cells with exogenous cysteine rescued invasion. Pharmacologic CTH inhibition suppressed glioblastoma invasion, while CTH knockdown slowed glioblastoma invasion in vivo.

CONCLUSIONS:

Our studies highlight the importance of ROS metabolism in invasive glioblastoma cells and support further exploration of the transsulfuration pathway as a mechanistic and therapeutic target.
296 Towards Nose-to-brain Inhibition of NFB: Activity of a Novel p65 Inhibitor in Glioblastoma and Feasibility of Intranasal Delivery With a Near-infrared Fluorescent HMC-Chitosan Nanoparticle
Authors: Tusa Lavieri Miguel Eduardo , Michel Michelot , Mohyeddinipour Sarah , Israel Liron , Wang Hongqiang , Miyaguchi Ken , Rajiv Subashni , Chatterjee Avradip , Watanabe Junji , Murali Ramachandran , Yu John
Published: March 2024

INTRODUCTION:

Constitutive NFκB inflammatory signaling is a driving force of tumor progression, immune evasion, and therapeutic resistance in glioblastoma (GBM). CRL1101 is a novel small molecule inhibitor of RelA (p65), a transcription factor of NFκB-mediated gene expression. Previously, we have shown that heptamethine carbocyanine (HMC) conjugated nanoparticles target GBM tumor sites via organic anion transporter proteins. The activity of CRL1101 in GBM has not been explored. Poor blood-brain barrier (BBB) penetration and theoretical toxicities related to p65 inhibition pose challenges to its implementation in vivo.

METHODS:

GBM transcriptomic analysis was performed using Gene Profiling Interactive Analysis. In vitro cytotoxicity and migration assays were performed in U87 and GL261. Western blot was used to confirm the mechanism of CRL1101. Quantitative PCR was used to assess the relative expression of NFκB-regulated genes. HMC-chitosan-CRL1101 nanoparticles were synthesized by cross-linking chitosan with HMC and their uptake was visualized using immunocytochemistry. For survival analysis, we implanted GL261 cells into immunocompetent mice and treated intranasally with HMC-chitosan-CRL1101.

RESULTS:

RelA is overexpressed in GBM relative to normal brain tissue. CRL1101 alone effectively kills U87 cells (IC50 = 16.0 uM) and prevents migration in vitro (p < 0.0001) by disabling the nuclear translocation of RelA. Treatment with CRL1101 was associated with a decrease in IL-8 (p = 0.01) and PD-L1 (p = 0.44) expression. HMC-chitosan-CRL1101 demonstrated an IC50 of 25.23 uM in U87. Near-infrared imaging confirmed intranasal delivery of HMC-chitosan-CRL1101 across the BBB in vivo.

CONCLUSIONS:

RelA-targeted NFκB inhibition with CRL1101 is a promising immunotherapeutic strategy in GBM. Intranasal nanoparticle delivery is a practical route to bypass the BBB and minimize systemic toxicities in mouse models of GBM, with expected survival benefit in vivo.
306 Endothelial Infiltrating Regulatory B Cells and NK T Cells Precipitate Inflammatory Cascade That Leads to Aneurysmal Rupture
Authors: Antonios Joseph Paul , Barak Tanyeri , Gultekin Batur , Yalcin Kanat , Adenu-Mensah Nana , Sujijantarat Nanthiya , Koo Andrew B. , Haynes Joseph , Hebert Ryan Matthew , Matouk Charles Christian , Gunel Murat
Published: March 2024

INTRODUCTION:

Current literature examining the mechanisms delineating intracranial aneurysm development and subsequent rupture is sparse. Studies from decades prior defined the aneurysm model as being one largely driven by flow changes. However, the scope of these models is limited and does not fully explain why only a subset of patients with existing intracranial aneurysms subsequently go on to rupture.

METHODS:

We obtained aneurysm endothelial lining from 20 patients with ruptured, unruptured, sentinel hemorrhage, and recurrent aneurysms during endovascular coil embolization, which were processed and analyzed using mass spectrometry.

RESULTS:

Compared to unruptured aneurysms, ruptured aneurysms had significantly increased infiltrating populations of NK cells (5.5% vs 1.4%, p < 0.01), regulatory B cells (27.6% vs 16.0%, p < 0.05), and cytotoxic CD8 T cells (23.7% vs 13.5%, p < 0.05). To understand whether these cells were recruited at the time of rupture or whether they were present prior to the ictus event, we examined aneurysms that were treated after presenting with sentinel hemorrhages – again these patients had that same population of early-NK cells (7.5%, p = 0.2), suggesting that these cells were present at the nexus point immediately prior to rupture. Further, the regulatory B cells were even more prominent in the sentinel population, (45.6%, p < 0.01).

CONCLUSIONS:

These findings all point to a complex, coordinated immune response that is driving the remodeling of the aneurysm vessel wall. We interpret the results to suggest that regulatory B cell driven destabilization of the aneurysmal wall leads to a series of events; namely the recruitment of NK cells, subsequent inflammatory cascade, and ultimate rupture. While there remains much to be understood about this multi-faceted picture, these findings provide the basis for further studies looking at targets for adjunctive immune therapies in both our unruptured and ruptured patient populations.
333 Financial Toxicity in Malignant Brain Tumors
Authors: Terrell Danielle , Camarano Joseph Gayle , Whipple Stephen Garrett , Guthikonda Bharat , Newman W. Christopher
Published: March 2024

INTRODUCTION:

As costs for cancer care continue to rise, ongoing development of novel therapeutics have increased the number of patients living with cancer. Cancer survivors are at increased risk of having high medical debt burdens, bankruptcy, delayed treatments, poor compliance with therapy, and even death as a result of financial toxicity.

METHODS:

Hospital billing database was queried for patients with ICD code C71 who had a bad debt discharge (unpaid balance) on record from 2020-2022. The corresponding hospital chart was then queried for demographic data, patient factors, and clinical factors.

RESULTS:

43 total patients had data available for analysis. The patient diagnoses were GBM (50%), Other (45.2%), followed by metastatic disease (4.7%). White patients had an average bad debt of $2742.10, while Black patients averaged $9851.6 (p = 0.017). 38.5% of White patients had more than $2000 in bad debt, compared to 81.8% of Black patients in that category (p = 0.014). The amount of debt differed significantly between tumor types; with 66.7% of GBM patients having more than $2000 in bad debt (p = 0.052). Difference in debt amount based on pre-operative employment status trended towards significance but fell short (p = 0.08). Most patients were unemployed (58.9%), followed by employed patients (33%), and retired patients (7.6%). 61.5% of employed patients had greater than $2000 in bad debt, compared with 56.5% of unemployed patients. 40% of patients had a pre-operative deficit, and of those patients, 54% had a bad debt amount in excess of $2000. 71% of patients without a pre-operative deficit had more than $2000 in bad debt.

CONCLUSIONS:

Bad debt is a major contributor to financial toxicity in patients with malignant brain tumors.
348 Comparison of Brain Functional Imaging of Pain States Using Resting-State fMRI and Multi-Delay pCASL to Clinical Scores of Pain in Chronic Low Back Pain Patients Implanted With Thoracic Spinal Cord Stimulation
Authors: Ashok Arjun Balaji , Oghli Yazan Shamli , Ailes Isaiah , Syed Mashaal , Kang KiChang , Naghizadehkashani Sara , Fayed Islam , Matias Caio M. , Mohamed Feroze , Krisa Laura , Alizadeh Mahdi
Published: March 2024

INTRODUCTION:

Thoracic spinal cord stimulation (tSCS) is an interventional option for patients with refractory chronic low back pain (cLBP). The use of functional imaging of brain regions involved in pain as a quantitative method to evaluate treatment effectiveness has not yet been studied.

METHODS:

pCASL data using 5 post-label delays (0.5-2.5s) alongside rs-fMRI data was gathered from five patients (4 M, 1F) post-tSCS with cLBP post-implantation with the SCS device turned off at a 3.0T scanner. Arterial transit time (ATT), cerebral blood flow (CBF), and cerebral blood volume (CBV) were derived from pCASL data. Amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF), degree of centrality (DC) and regional homogeneity (ReHo) were derived from rs-fMRI data. These data were registered against a pain-ROI atlas. The following clinical pain scores were assessed in the same five patients: Numerical Pain Rating Scale (NPRS), Visual Analogue Scale (VAS), Central Sensitization Inventory (CSI), Oswestry Disability Index (ODI), Pain Catastrophizing Scale (PCS), Pittsburgh Sleep Quality Index (PSQI) and Hospital Anxiety and Depression Scale (HADS). Predictive linear associations between pain ROIs and clinical scores were investigated using linear regression.

RESULTS:

Significant linear associations (p-value < 0.001) were found between pCASL-derived ATT to the dorsolateral prefrontal cortex (DLPC) and the NPRS; CBF to the ventral posterolateral thalamus (VPL) and the VAS, and of the posterior cingulate cortex (PCC) and the VAS; CBV of the posterior short gyrus (PS) and the VAS; and rs-fMRI-derived fALFF of the amygdala and the CSI.

CONCLUSIONS:

A comparison of functional imaging results and clinical pain scores suggest predictive relationships between resting-state function/brain perfusion in regions involved in pain perception and processing and various clinical pain assessments.
357 Postoperative Outcomes and Decreases in Pain Medication Utilization Following Nucleus Caudalis DREZ Lesioning for Painful Trigeminal Neuropathy: A Case Series
Authors: Venkatraman Vishal , Futch Brittany Grace , Padron Kevin Bode , Parente Beth , Rahimpour Shervin , Lad Nandan P.
Published: March 2024

INTRODUCTION:

Painful trigeminal neuropathy is characterized by treatment-resistant trigeminal pain. Nucleus Caudalis Dorsal Root Entry Zone lesioning (NC-DREZ) has been utilized to treat this condition, but changes in medication utilization has not been studied in this population.

METHODS:

We retrospectively reviewed patients who underwent NC-DREZ at an academic medical center for the treatment of painful trigeminal neuropathy between March 2014 and December 2022, with a minimum 30-day follow-up. Postoperative complications, emergency department visits, readmissions, reoperations, changes in patients' subjective pain, and the longitudinal dosage of pain medications were collected as outcomes. The Fisher's exact and Kruskal-Wallis tests, with alpha set at 0.05, were used to compare the proportion and doses of medications used at each timepoint.

RESULTS:

Thirty-nine patients were included (mean age 55.7 years, 66.7% female) Prior interventions included trigeminal ablation (35.9%), microvascular decompression (59.0%), and stereotactic radiosurgery (41.0%).Twelve patients (30.8%) had postoperative complications, including five with transient ataxia and two with pseudomeningocele. Nine patients (23.1%) visited the ED after surgery, and 7 (17.9%) were readmitted. The rate of opioid use decreased from 56.4% at baseline to 32.3% six months following surgery (p = 0.03). Additionally, the use of carbamazepine, gabapentin, pregabalin, duloxetine, and amitriptyline decreased. One year after surgery, 11/26 patients (42.3%) reported sustained pain relief.

CONCLUSIONS:

In this case series of NC-DREZ patients, we demonstrated that postoperative complications and subjective pain outcomes were comparable to those previously reported in the literature. Importantly, we demonstrated a reduction in the use of opioids six months after surgery. This study's findings support the use of NC-DREZ as an alternative treatment for painful trigeminal neuropathy. Large scale prospective studies are needed to confirm these results.
363 Anatomic Study of Cervical Neural Foraminal Dimensions, Interpedicular Distance, and Disc Space Height From C2-T1 Using Computed Tomography of 1,000 Patients
Authors: Razzouk Jacob Anees , Case Trevor , Sajdak Grant , Kricfalusi Mikayla , Nguyen Kai , Taylor Rachel , Vyhmeister Ethan , Kagabo Whitney , Carter Mei , Carter Davis , Ramos Omar , Cheng Wayne K. , Danisa Olumide A.
Published: March 2024

INTRODUCTION:

The normative relationships among cervical neuroforaminal dimensions (NFD), interpedicular distance (IPD), and disc space height (DSH) remain unknown.

METHODS:

We reviewed CT imaging of 1,000 patients between 18 and 35 years of age without spinal pathology to measure cervical NFD, defined as follows: foraminal height, sagittal anterior-to-posterior width, and area. Anterior, middle, and posterior DSH, and IPD were also measured. Interobserver reliability was assessed via the intraclass correlation coefficient (ICC) two-way mixed model on absolute agreement.

RESULTS:

Bilateral NFD followed bimodal distribution patterns moving caudally from C2-T1, whereas DSH measurements exhibited multimodal distribution patterns and IPD demonstrated a unimodal distribution clustered at the lower cervical spine. Significant differences were observed in NFD, DSH, and IPD measurements with respect to patient sex and race taking into consideration patient demographic and anthropometric characteristics. The African American cohort demonstrated the smallest NFD, DSH, and IPD measurements, followed by the Hispanic cohort, followed by the Caucasian cohort. Weak-to-moderate correlations were observed among NFD, DSH, and IPD measurements across all levels.

CONCLUSIONS:

This study describes 70,800 DSH, NFD, and IPD measurements from C2-T1 using CT imaging of young patients without spinal pathology. Findings from this study may provide normative guidelines necessary to establish the foundation for diagnosis of cervical neuroforaminal stenosis. Surprisingly, this study found no strong, or even moderate, correlations between normative NFD, DSH, and IPD measurements across all levels from C2-T1. Patient sex, ethnicity, and height are associated with NFD, DSH, and IPD, though patient weight is not.
380 2021 WHO Grading Scheme Provides Minimal Incremental Improvement in Prognostic Stratification of a Retrospective IDH-Mutant Astrocytoma Cohort Compared to 2016 WHO Grading Scheme
Authors: Kalluri Anita , Myneni Saket , Parker Megan , Weber-Levine Carly , Arshad Umar , Shaw Jacob , Sarlin Samantha , Rempert Ashley , Dunseath Chloe , Materi Joshua , Raj Divyaansh , Rincon Torroella Jordina N. , Ye Xiaobu , Lucas Calixto-Hope , Bettegowda Chetan
Published: March 2024

INTRODUCTION:

The 2021 WHO Classification of CNS Tumors introduced prognostically relevant molecular alterations (ex. CDKN2A homozygous deletion) into grading criteria for select tumors.

METHODS:

We retrospectively identified 176 adult IDHmAstro patients with available next-generation sequencing (NGS). All tumors were regraded based on the 2021 and 2016 WHO grading schema using relevant histopathological (mitotic rate, microvascular proliferation, necrosis) and molecular (CDKN2A) features. The prognostic ability of each grading schema was evaluated with Kaplan-Meier and multivariate Cox Regression analyses.

RESULTS:

The cohort consisted of 76 grade 2 (43.2%), 45 grade 3 (25.6%), and 55 grade 4 (31.3%) IDHmAstro cases using the 2021 grading schema. Only four patients (2%) had a grade change from the 2016 WHO grading scheme - one prior 2016 WHO grade II and three grade III tumors, all regraded to Grade 4 based on present CDKN2A homozygous deletion. When assessed based on both classification schemas, WHO Grade 4/IV tumors were associated with lower OS than Grade 2/II tumors (HR [95% CI]: 4.20 [1.09–16.22], P = 0.037 per 2016 and 3.82 [1.04–14.09], P = 0.044 per 2021). There were no significant differences in OS between Grade 2/II and Grade 3/III tumors or Grade 3/III and Grade 4/IV tumors within either grading schema.

CONCLUSIONS:

Only four patients had a change in grade, implying the majority of IDHmAstro patients would have received similar treatment using either grading schema. Interestingly, outcomes for grade 3/III IDHmAstro were not significantly different from grade 2/II or grade 4/IV IDHmAstro in either schema, suggesting that grade 3/III tumors represent a biologically heterogeneous group. These results should be validated in other series but underscore a continued unmet need for novel biomarkers to improve IDHmAstro risk-stratification.
381 Glioma Three-Dimensional Shape Predicts Underlying Genetic Mutations
Authors: Warman Pranav , Adil Syed M. , Seas Andreas , Sexton Daniel , Calabrese Evan , Lad Nandan P. , Kolls Brad , Fuller Anthony , Dunn Timothy , Friedman Allan H. , Hasan David M. , Komisarow Jordan M. , Cook Steven H. , Codd Patrick James , Zomorodi Ali R. , Fecci Peter Edward , Patel Anoop , Grant Gerald A. , Tralie Christopher
Published: March 2024

INTRODUCTION:

Phenotype is the detectable expression of genotype. Despite this, little is known about how the three-dimensional structure of brain tumors correlates with their genetic biomarkers.

METHODS:

The UCSF-PDGM dataset was filtered for histopathologically-proven gliomas. Segmentation masks of the enhancing tumor, non-enhancing/necrotic tumor, and surrounding FLAIR abnormality were obtained from each patient’s preoperative brain MRI. All tumors were evaluated for IDH mutations and 1p/19q codeletion; all grade III and IV tumors were tested for MGMT methylation status. The segmentation masks were processed to create topological features describing the tumor’s 3D shape. These features, without other clinical variables, were used in a custom machine learning pipeline to predict the presence of IDH mutations, 1p/19q codeletion, and MGMT methylation.

RESULTS:

After filtration, 103 of 494 gliomas tested had an IDH mutation, 29 of 494 had a 1p/19q codeletion, and 247 of 409 had methylation of MGMT. On the blinded test-subset, the machine learning model, using only features describing shape, rendered an AUROC of 0.902 (95% CI: 0.875-0.929), specificity of 90.3% (83.9%-96.6%), and sensitivity of 75.7% (68.0%-83.3%) for IDH mutation. For 1p/19q codeletion, we found an AUROC of 0.949 (0.908-0.990), specificity of 94.5% (84.3%-100%), and sensitivity of 86.6% (79.6%-93.6%). For MGMT methylation, the performance was poor with an AUROC of 0.445 (0.385-0.504).

CONCLUSIONS:

The three-dimensional shape of a glioma may be used to predict the presence of some key underlying genetic mutations before biopsy. Additional research is needed to validate this, improve its fidelity, and generalize it to other biomarkers.
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.