bluuebunny/crossref_metadata_2025 huggingface dataset:
209 Detection and Characterization of Glioma and Therapy-associated Biomarkers in CSF
Authors: Carlstrom Lucas P. , Riviere-Cazaux Cecile , Casabella Amanda , Rahman Masum , Burns Terry C.
Published: March 2022

INTRODUCTION:

Molecular characterization of human gliomas currently requires access to tissue samples. While tumor-associated cell-free DNA has been detected in CSF and cell-free DNA, utility is limited to those harboring specific detectable mutations. Gliomas with IDH-mutations produce high levels of D-2-Hydroxyglutarate (D2-HG), a stable and quantifiable oncometabolite that is correlated with tumor burden as assessed within the tumor mass. However, the reliability of D2-HG in CSF as an in vivo pharmacodynamic biomarker is unknown.

METHODS:

A brain tumor CSF biorepository has been launched, including prospective samples obtained intra-operatively and via ventriculoperitoneal shunts, Ommaya reservoirs, or lumbar punctures at clinically-relevant time points. Analyses included targeted and untargeted metabolomic analyses, and PCR for patient-specific chromosomal junctions utilizing primers specific to junctions predicted to be stable over time.

RESULTS:

Twenty-one CSF samples were utilized for one or more analyses. Patients with IDH-mutant gliomas had over twenty-fold higher levels of D2HG in CSF (median 4.1 uM, range 1.6-13.2 uM, n = 7) compared to IDH-wild type gliomas (median 0.19 uM; range 0.89-0.35, n = 14) (p < 0.001). A total of 13 CSF samples from 8 patients were evaluated via targeted and untargeted untargeted metabolomics. 282 metabolites were identified consistently in all 13-samples. In addition to IDH-mutant status, signatures were identified conveying patient identity Correlation and Principle component analyses identified distinct clustering of CSF samples by patient identify, prior radiation status, and clinical/collection variables including plasma contamination, and NPO status. Samples obtained after prior radiation were enriched for curated metabolite sets including TCA cycle and Warburg effect. Relative CNS levels of several pharmacologic agents (acetaminophen/levetiracetam/mannitol/caffeine) could also be quantified from the untargeted metabolomic profiles. Multiple unique patient tumor-specific chromosomal junctions were robustly quantifiable in all evaluated CSF samples, but no plasma samples, correlating with tumor burden across serial samples.

CONCLUSION:

Mutation-specific oncometabolites, cell-free DNA mutations and signatures of prior therapy were sensitively and dynamically detected in intra-operative and ventricular CSF samples. CSF may provide an underutilized resource to monitor glioma burden and phenotype.
211 Deep Phenotyping Reveals Germline Determinants of Disease Severity in Neurofibromatosis Type 2
Authors: Celano Emma , Nwokoye Diana , Chittiboina Prashant
Published: March 2022

INTRODUCTION:

Neurofibromatosis type 2 (NF2) is an autosomal dominant tumor predisposition syndrome with central and peripheral nervous system tumors and non-neoplastic manifestations including peripheral neuropathy. NF2 presents with a large variation in penetrance and severity. Although germline nonsense and frameshift NF2mutations are hypothesized to confer severe disease, the relationship between mutation type and manifestations of this disease is not completely understood.

METHODS:

Patients (n = 169) with NF2 (Manchester criteria) were enrolled in a Natural History protocol (NCTNCT00598351). Deep phenotypic profiles were created (serially for 5 years) including clinical evaluations, self-reported functional measures, lifetime interventions (surgical, radiation and drug treatments), and imaging (tumor number, type and volume using volumetric MRI of the neuroaxis). Validated germline mutation data (n = 68) was used to examine relationships between genotype and phenotype with attention to NF2 mutation type (indel/large deletion), genomic effect (missense/nonsense/frameshift), predicted protein effect (truncating/non-truncating) and location (exonic/intronic/splice-site).

RESULTS:

Tumor burden varied greatly between patients (tumor number range 1-165, median 25). We found that cranial meningiomas were a major determinant of total tumor burden. Total tumor burden (number and volume) was associated with worse KPS and decline in KPS over the study protocol (p < 0.001). We found that truncating mutations in exons 11-12 were associated with more severe disease in terms of tumor number on MRI (p = 0.0439).

CONCLUSION:

This is the first large scale study to deeply phenotype patients with NF2 including longitudinal analysis and demonstrates several previously unrecognized trends related to germline mutations type, imaging findings, and measures of disease severity.
304 Cannabis Use and Increased Non-aneurysmal Subarachnoid Hemorrhage in the Last Decade
Authors: Lai Pui M. R. , Ng Isaac , Gormley William , Patel Nirav J. , Frerichs Kai U. , Du Rose
Published: March 2022

INTRODUCTION:

Spontaneous subarachnoid hemorrhage is often due to rupture of an intracranial aneurysm, but some patients present with no identifiable source. Increased incidence of non-aneurysmal subarachnoid hemorrhage (naSAH) has been reported over time.

METHODS:

We performed a retrospective analysis of naSAH from 2008-2017 to determine the rate of naSAH change over time, and its association with cannabis use. Univariable and multivariable regression analyses were performed to study the trend over time, radiographic patterns of hemorrhage, and clinical outcome at the time of discharge. Additionally, we compared the rate of naSAH with the rate of aneurysmal SAH (aSAH) to adjust for changes in hospital volume and prevalence/reporting of cannabis use in the population over time.

RESULTS:

A total of 86 naSAH and 328 aSAH patients were identified, with an increase in naSAH over time compared to aSAH (p = 0.0034). Increased cannabis use was associated with naSAH (OR 2.1, 95% CI 1.1, 4.1, p = 0.035), but not aSAH over time. Cannabis use was also associated with different subarachnoid hemorrhage patterns (p = 0.0065) in naSAH. Multivariable analysis demonstrated good neurological outcome after naSAH to be inversely associated with cocaine use (OR 0.008 [0.002-0.4]), ventriculostomy placement (OR 0.004 [0.03-0.50]), and anticoagulant use (OR 0.016 [0.003-0.54]), but was not associated with cannabis use.

CONCLUSION:

As cannabis use becomes more prevalent with legalization, it is important to further investigate this association with spontaneous SAH.
306 Nationwide Readmission Rates and Costs for Patients With Surgical Evacuation of Nontraumatic Subdural Hematomas: Part 1—Craniotomy
Authors: Shaftel Kelly T. , Cole Tyler S. , Jubran Jubran H. , Schriber Tyler , Little Andrew S.
Published: March 2022

INTRODUCTION:

Despite patients experiencing high recurrence and readmission rates after surgical management of nontraumatic subdural hematomas (SDHs), few studies have examined the causes and predictors of unplanned readmissions in this population on a national scale.

METHODS:

Using the Nationwide Readmissions Database, we identified patients who underwent craniotomy for nontraumatic SDH evacuation (2010-2015) using a retrospective cohort observational study design. National estimates and variances within the cohort were calculated after stratifying, hospital clustering, and weighting variables.

RESULTS:

Among 49,013 patients, 10,643 (21.7%) had at least 1 readmission within 30 days of their index treatment and 38,370 (78.3%) were not readmitted. Annual readmission rates did not change during the study period (P = 0.74). The most common primary causes of 30-day readmissions were recurrent SDH (37.1%), venous thromboembolism (12.9%), and delayed hyponatremia and SIADH (syndrome of inappropriate antidiuretic hormone secretion) (12.8%). Comorbidities that independently predicted readmission included congestive heart failure, chronic obstructive pulmonary disease, coagulopathy, diabetes mellitus, liver disease, lymphoma, fluid and electrolyte disorders, metastatic cancer, peripheral vascular disease, psychosis, and renal failure (P = 0.03). Household income in the 51st-75th percentile was associated with a decreased risk of readmission.

CONCLUSION:

National trends in 30-day readmission rates after nontraumatic SDH treatment via craniotomy provide quality benchmarks that can be used to drive quality improvement efforts on a national level.
308 Comparison of Demographics and Outcomes Between Surgical and Conservative Management in Patients Undergoing Treatment for Posterior Cranial Fossa Hemorrhages—Experience from a Low-Resource Country
Authors: Aziz Hafiza F. , Hani Ummey , Suleman Fatima , Qadeer Namra , Nazir Danyal , Shamim Shahzad M. , Zahid Nida
Published: March 2022

INTRODUCTION:

Posterior Cranial Fossa Hemorrhages (PCFH) often require surgical intervention. However, comparison between outcomes in surgical vs conservative management has ben rarely sought in the literature.

METHODS:

Retrospective review of patient data was conducted under IRB approval. All patients managed for PCFH at Aga Khan University, Karachi, Pakistan, from January 2009 to December 2020 were included. SPSS (IBM) was utilized to analyze data.

RESULTS:

Surgery vs Conservative: Out of 79 patients, 30.7% vs 69.6% patients underwent each, respectively. Mean age 51 +/- 16.4 vs 56+/-10.7. Males (62.5% vs 70.9%), and females (37.5% v 29.1%). Median GCS at presentation was 9 vs 13. Surgery was indicated at initial presentation (54.2%) or if clinical deterioration was observed (29.2%). Radiographically, significant differences were noted in the mean Intracranial Hemorrhage Score (ICH) (3 vs 2; p = 0.036), maximum hematoma diameter (3.37 vs 2.31 cm; p < 0.001), brainstem involvement (2 vs 32; p < 0.001), 4th ventricle abnormality (100% vs 23%; p < 0.001); intraventricular hemorrhage (78.3% vs 29.4%; p < 0.001), tight posterior fossa (87% vs 37.3%; p < 0.001); clot location (hemispheric vs brainstem; 41.7% vs 52.9%; p = 0.001); median temporal horn width (2.1 vs 0.38 cm; p < 0.001) and clot volume (14.7 cm3 vs 5.5 cm3; p < 0.001). Differences in median length of hospital, ventilator, and ICU stays (14.5 vs 4; p < 0.001, 1.5 vs 0; p < 0.001 and 3 vs 0 days; p < 0.001 respectively), tracheostomy (5% vs 1%; p = 0.003), Infection rate (66.6 vs 29.1%; p < 0.001) and median overall survival (53 vs 10 months; p = 0.046) were all significant.

CONCLUSION:

While surgery increased survival, significant morbidity and late hospital discharge was observed in patients undergoing surgery for PCFH.
310 Impact of Obesity on Morbidity Associated With Endoscopic Spine Surgery
Authors: Bergquist Julia , Greil Madeline , Hofstetter Christoph P.
Published: March 2022

INTRODUCTION:

Obesity has profound impact on traditional spine surgery and is associated with increased surgical complexity and postoperative complications.

METHODS:

A retrospective review of a single-surgeon database was conducted for all adult patients undergoing unilateral laminotomies for bilateral decompression between November 2015 and March 2021. Data collected included operating room induction time, procedure time, length of hospital stay, use of analgesics, post-operative complications, post-operative pain reduction measured by visual analogue scale (VAS), and quality of life measured by EQ-5D-5L and Oswestry Disability Index (ODI). For statistical analysis, patients were categorized into non-obese and obese groups as defined by the World Health Organization based on body mass index (BMI, kg/m2): 18-29.9 and 30+. Data between groups were compared using Kolmogorov-Smirnov test. Recovery complications, analgesics use, and need for same-level revision were assessed using logistic regression.

RESULTS:

Our patient cohort included 181 patients with an average age of 63.5 years. Patients with higher BMI suffered more pronounced back pain disability (P < 0.01) preoperatively. Operative details including number of segments operated on were similar within our cohort. Surgical induction times increased significantly with BMI (Pearson correlation 0.228, P < 0.01), while procedure times were not affected. Mean follow-up was 22.8 +/-1.4 months. There were no differences between obese and non-obese patient populations’ low-level analgesic use at two weeks post-operation, need for revision, and degree of VAS, ODI, and EQ-5D-5L improvement. However, there were significant positive correlations between BMI and length of hospital stay (P < 0.009), two-week post-operative narcotic use (P = 0.001), and postoperative complications (P = 0.027).

CONCLUSION:

Working channel endoscope can mitigate some procedural challenges related to obesity, however, the obese patient population requires increased health care resources and suffers from more frequent postoperative complications.
312 Dural Injury Treatment with a Full-endoscopic Approach: A Case Report and Description of the Surgical Technique
Authors: Sandon Luiz H. , Bergamaschi João P.
Published: March 2022

INTRODUCTION:

The incidence of dural sac injuries during lumbar decompression surgery is highly variable, ranging from 1% to 17% in the literature. When present, these lesions can be small and punctate. Repairs are unnecessary; however, more complex, larger lesions may occur, in which repairs become necessary. Conversion to open surgery and repair in the traditional manner is usually recommended.

METHODS:

A technical description showing the possibility of primary correction of dural injury via endoscopy.

RESULTS:

A 5–0 Prolene thread with two needles was used. One of the needles must be passed through the working channel of the endoscope to the injury site. After the needle passes through the two edges of the lesion, the two ends of the thread are externalized to make the sliding knot. The execution of this knot allows it to slide to the lesion site without the need to pull the two ends of the wire. Bergamaschi's technique differs from Youn's technique by performing an RHAP sliding knot (reversing half-hitch alternating post knot) instead of a simple knot. The tension must be applied equally at both ends to tighten the knot.

CONCLUSION:

Endoscopic repair of dural lesions is a challenge for spine surgeons. The Bergamaschi technique described here represents an advance method of treatment capable of allowing more surgeons to treat dural injuries without the need to convert to open surgery.
313 Sacroiliac Joint Fusion Using Robotic Navigation: Technical Note and Case Series
Authors: Wang Timothy Y. , Bergin Stephen M. , Murphy Kelly R. , Mehta Vikram , Sankey Eric W. , Abd-El-Barr Muhammad M. , Grossi Peter M. , Than Khoi Duc
Published: March 2022

INTRODUCTION:

Degenerative sacroiliac (SI) joint disease can cause significant pain and disability. Patients undergoing SI fusion can oftentimes experience significant improvements in pain and quality of life.

METHODS:

Patients undergoing standalone SI joint fusion from July 2020 through June 2021 were retrospectively enrolled. Demographic and comorbid variables collected included age, sex, body mass index, and laterality. Recorded operative variables included operative time, estimated blood loss, and any intraoperative complications. Pain scores in the post-anesthesia care unit (PACU) were recorded using the visual analogue scale (VAS) every 30 minutes, as were total morphine equivalents for PACU administered intravenous and oral narcotic pain medications according to pain scales. Length of stay and any postoperative complications including 30-day inpatient admissions or emergency department (ED) presentations were also recorded. Intraoperative radiation exposure was also recorded.

RESULTS:

A total of 8 patients were analyzed. Average patient age was 65.6 ± 7.6 years with BMI of 28.2 ± 3.6 kg/m2. Four (50.0%) patients were female and equal numbers of left and right-sided SI joint fusions were performed. Average operative time was 56 ± 9 minutes, and average estimated blood loss was 22.5 ± 18.7cc. Average intraoperative radiation exposure was 12.7 ± 6.7 mGy and there were no intraoperative complications. Average pain scores in PACU were 5.1 ± 1.0 with average maximum pain score of 7.6 ± 1.7 and average minimum pain score of 2.0 ± 2.2. Average narcotic administration in PACU was 22.8 ± 11.1 morphine equivalents. Average length of stay was 0.4 ± 0.8 days, with 75% of patients discharged on the same day of surgery. Two patients required inpatient stay: one patient required intravenous pain medications overnight and one patient had shortness of breath without clear etiology, resolved without sequela. No patients presented back to the ED or were admitted within 30-days of surgery.

CONCLUSION:

Robot-navigated SI joint fusion is a feasible and reproducible method for addressing refractory sacroiliac joint disease. Further investigation on clinical outcomes and long-term fusion rates is needed, as are studies comparing robot-navigated SI joint fusion to more traditional techniques.
322 Neuroinflammatory Biomarkers for Traumatic Brain Injury Diagnosis and Prognosis: Results From the TRACK-TBI Pilot Study
Authors: Yue John K. , Kobeissy Firas , Yang Zhihui , Xu Haiyan , Deng Hansen , Han Kasey , Puccio Ava , Sun Xiaoying , Rabinowitz Miri , Markowitz Amy , Okonkwo David O. , Diaz-Arrastia Ramon , Manley Geoffrey T. , Wang Kevin
Published: March 2022

INTRODUCTION:

The relationship between systemic inflammation and traumatic brain injury (TBI) is complex. Primary injury triggers release of pro- and anti-inflammatory cytokines, chemokines, and alarmins/alarmin response proteins.

METHODS:

The prospective, multicenter TRACK-TBI Pilot study was used. Subjects received head CT and blood draw within 24h of TBI. Biomarkers were extracted from plasma and included: cytokines (IL-6, IL-10, IL-15, IL-16), chemokines (monocyte chemoattractant protein 4 (MCP-4), thymus activation-regulated chemokine (TARC)), alarmin/alarmin response proteins (high mobility group box 1 (HMGB-1), serum amyloid A (SAA), c-reactive protein (CRP)), and others. Area Under the Curve (AUC) was used to evaluate marker discriminability for clinical diagnosis (TBI vs. orthopedic control (OC)/healthy control (HC)), TBI severity (GCS 3-12 vs. 13-15), radiographic injury on CT, and unfavorable vs. favorable 3- and 6-month outcome (Glasgow Outcome Scale Extended (GOSE) 1-4 vs. 5-8). Statistical significance was assessed at p<0.05.

RESULTS:

One-hundred sixty-eight TBI subjects, 28 OC, and 18 HCs were included. Markers associated with TBI clinical diagnosis were: IL-6, IL-10, IL-16, MCP-4, TARC, HMGB-1, SAA, CRP. Markers for TBI severity: IL-6, IL-10, IL-15, IL-16, TARC, HMGB-1, SAA, CRP. Markers for radiographic TBI: IL-6, IL-10, IL-15, IL-16, HMGB-1, SAA, CRP. Predictors (AUC > 0.70) for TBI vs. OC: HMGB-1 (AUC = 0.84), IL-16 (AUC = 0.78), TARC (AUC = 0.73). Predictors for TBI vs. HC: IL-6 (AUC = 0.92), IL-10 (AUC = 0.87), HMGB-1 (AUC = 0.87), IL-16 (AUC = 0.72). Predictors for radiographic TBI: SAA (AUC = 0.77), IL-6 (AUC = 0.76), CRP (AUC = 0.73). IL-15 predicted 3- and 6-month GOSE (AUC = 0.74/0.70, respectively). SAA predicted 6-month GOSE (AUC = 0.70).

CONCLUSION:

We identified a distinct profile of cytokines, chemokines and alarmin/alarmin response proteins detectable systemically within 24h of TBI. These markers may have unique importance in TBI detection, severity differentiation, and prognosis. Future research on neuroinflammatory pathways will elucidate the evolution of injury and yield potential targets for therapeutic intervention.
326 Concussion Subtype Symptomatology in Complicated Mild Traumatic Brain Injury Patients
Authors: Knott Maxon , Folz Caroline , Viel Amy , Thomas Andrea , Ngwenya Laura B.
Published: March 2022

INTRODUCTION:

Post-concussive symptom scales (PCSS) can help discern recently defined concussion subtypes such as cognitive, ocular-motor, headache/migraine, vestibular, and anxiety/mood with concussion-associated sleep disturbance and cervical strain. However, there is limited knowledge as to the utility of using subtype symptomatology in the assessment of complicated mild traumatic brain injury (TBI) patients.

METHODS:

We included mild TBI patients who presented to a neurosurgery TBI clinic and had completed a Rivermead Post Concussion Questionnaire (RPQ). Patient demographic factors such as age, sex, mechanism of injury, and arrival GCS were extracted from the medical record. Patients were characterized into groups based on imaging findings including epidural and subdural hematomas (extra-axial), or intraparenchymal, subarachnoid, or intraventricular blood (intra-axial) or both. We excluded patients with negative head CT results. We used the RPQ itemized questions to define symptom subtypes. Differences between groups were analyzed using an ANOVA and general linear model analysis in SPSS.

RESULTS:

We included a total of 163 patients, 52 showed intra-axial bleeds, 40 showed extra-axial bleeds, and 71 exhibited both intra- and extra-axial bleeds. ANOVA results show statistically significant differences in ocular-motor (p = 0.035), headache/migraine (p = 0.010), and vestibular (p = 0.032) subtype scores between groups. Specifically, multiple comparisons revealed the extra-axial means were lower in the ocular-motor (0.947 ± 0.235 SEM vs. 2.13 ± 0.312; p = 0.011), headache/migraine (1.50 ± 0.310 vs. 2.79 ± 0.258; p=0.003), and vestibular (1.18 ± 0.226 vs. 2.09 ± 0.198; p = 0.011) subtypes. Further analysis to determine the effects of several covariates found that age contributed significantly to the associated condition of sleep disturbance (p=0.049).

CONCLUSION:

Patients with complicated mild TBI have post-injury symptoms that can be classified into concussion subtypes. Patients with extra-axial bleeds exhibited consistently better subtype scores compared to those with intra-axial bleeds. Understanding subtype symptomatology may allow for subtype directed therapy to improve symptom recovery for mild TBI patients.
341 SOncomagnetics: A Potential New Noninvasive Magnetic Stimulation Technology to Treat Glioblastoma
Authors: Baskin David S. , Sharpe Martyn , Hambarde Shashank , Helekar Santosh
Published: March 2022

INTRODUCTION:

A new noninvasive oscillating magnetic field (OMF)-generating device called Oncomagnetic (OM) device, developed in our laboratory, disrupts mitochondrial electron transport to elevate intracellular reactive oxygen species (ROS) levels in patient derived glioblastoma (GBM) cells.

METHODS:

GBM cell death, ROS elevation and caspase 3 activation were studied by bright-field and fluorescence microscopy involving specific fluorescent probes. Device treatment of FOXN1-Nude mice with GBM xenografts was for 4 hours twice a day. Treatment of a 53-year-old male patient with recurrent GBM was done under a compassionate use protocol for 2–6 hours each weekday. Contrast-enhanced MRI scans assessed tumor size.

RESULTS:

OMF caused selective death of GBM cells, but not normal human cortical neurons and astrocytes. It altered mitochondrial oxygen consumption, increased mitochondrial and cellular ROS, and activated caspase 3. The overall survival of xenografted mice was prolonged by 6 days with treatment. A 26-day device treatment was well tolerated by the patient and decreased contrast-enhanced tumor volume by >30%. Patient’s autopsy after his death from closed head injury showed treatment effect, no tumor mass, and some evidence of active tumor.

CONCLUSION:

Noninvasive stimulation with the OM device is a potential powerful new treatment for GBM involving a novel mechanism of action.
346 Cancer-associated Fibroblasts in Glioblastoma Mouse Model Impact the Lymphoid Cells in the Tumor Microenvironment
Authors: Kim Timothy Y. , Srivastava Siddhartha , Patel Kisha K. , Pant Ayush , Lim Michael
Published: March 2022

INTRODUCTION:

Cancer-associated fibroblasts (CAFs) have been demonstrated to play a prominent role in various solid tumors by remodeling and reprogramming the tumor microenvironment. Recently, they have been identified in glioblastoma (GBM) patients and believed to have a protumoral effect in GBM progression. Not only have CAFs been found to affect the myeloid compartment, but also the lymphoid compartment. Studies have shown that CAFs may mediate dysfunction of CD8 T-cells, decrease their cytotoxicity, and induce apoptosis.

METHODS:

6-week C57BL/6J wild-type female mice were intracranially implanted with either Gl261-luciferase (Gl261-luc) tagged cells alone or in combination with NIH/3T3 embryonic fibroblasts. Mice were monitored for survival in 4 arms (Gl261 vs Gl261 + anti-PD-1 vs Gl261 + NIH3T3 vs Gl261 + NIH3T3 + anti-PD-1) or sacrificed on post-implantation day 18 for flow cytometry analysis. Anti-PD-1 treatments occurred on post-implantation D10, 12, and 14. For flow cytometry, immune cells were isolated, were plated in a 96-well plate, and stained with antibodies for CD45, CD3, CD8, PD1, TIM3, LAG3, IFN-gamma, and TNF-alpha.

RESULTS:

The fibroblast-glioblastoma arms had significantly worse survival than non-fibroblast arms. Anti-PD-1 significantly improved survival in the fibroblast-glioblastoma arm. Fibroblast arms had statistically significant increased Cd8+ T-cell infiltration, reduced TIM-3 expression, reduced LAG3 expression, reduced IFN-gamma production in CD8+ T-cells, and trended toward significantly increased PD-1 expression.

CONCLUSION:

The addition of fibroblasts led to greater CD8+ T-cell infiltration but resulted in worse survival and an overall exhausted T-cell phenotype, as evidenced by equal or increased expression of LAG3 and PD-1. This corroborates why anti-PD-1 administration resulted in greater survival. Interestingly, TIM-3 expression was decreased in the fibroblast arms.
349 Locally Recurrent GBM Treated with Resection and Immediate Initiation of Radiation Therapy: Results from a Prospective Trial
Authors: Smith Kris , Nakaji Peter , Thomas Theresa , Pinnaduwage Dilini , Wallstrom Garrick , Brachman David
Published: March 2022

INTRODUCTION:

Treatment for recurrent GBM remains problematic. Resection (R) alone is insufficient, and survivals achieved with systemic therapy with or without radiation therapy (RT) are typically <1 year.

METHODS:

From 2/2013-2/2018, locally recurrent GBM were treated in a single arm trial (ClinicalTrials.gov, NCT#03088579) of R plus implantation of a surgically targeted radiation therapy (STaRT) device utilizing Cs-131 in bioresorbable collagen tiles (GammaTile, GT Medical Technologies, Tempe AZ USA).

RESULTS:

28 patients (pts) were treated, 20 at first recurrence (range 1-3). Median age 58 (range 21-80), KPS 80 (60-100), female:male ratio 10:18. Median OS 10.7 mo., radiographic LC 8.8 mo., and no first failure was local. MGMT, KPS, and sex were non-predictive. Post hoc analysis disclosed after R+STaRT, 17 pts (54%) received >1 cycle of systemic (Sys) treatment (“Sys+”) and 13 pts (46%) did not (“Sys- “). Sys was given as adjuvant, salvage, or both, either alone or in combination. 15 pts received bevacizumab (BEV), 12 temozolomide (TMZ) and 8 lomustine (CCNU). Median OS (mo.) for Sys+ vs. Sys- was 15.1/6.5 (hazard ratio (HR) .38, p = .017); OS for BEV+ vs. BEV- was 16.7/4.5 (HR .38, p = .017), TMZ+ vs. TMZ- 17.5/6.7 (HR .40, p = .025) and for CCNU+ vs. CCNU- 17.5/7.9 (HR .61, p = .25), respectively. LC was 11.4 mo. for Sys+ vs. 2.1 mo. for Sys- (HR .44; p = .16). Three attributed serious AE occurred, 1 wound infection requiring surgery and 2 radiation brain effects, managed medically.

CONCLUSION:

Post hoc analysis suggests R+STaRT+Sys may have the potential to impact OS in locally recurrent GBM, possibly by allowing sufficient time for biologically slower but effective treatments to have an impact.
355 Use of Novel Telemedicine Software to Automate Cranial Nerve and Neuro-Ophthalmic Remote Testing
Authors: Mouchtouris Nikolaos , Yu Si Yuan , Karsy Michael , Sergott Robert , Moster Mark , Farrell Christopher J. , Evans James J.
Published: March 2022

INTRODUCTION:

Despite the rapid surge in telemedicine use due to the COVID-19 pandemic, there is still a paucity of telemedicine tools for the remote assessment of patients with neurological diagnoses. Current telemedicine platforms lack the capabilities to perform thorough cranial nerve and neuro-ophthalmic testing. To address this need, we developed a novel software that patients can use to undergo cranial nerve and neuro-ophthalmic testing remotely via their own personal computer.

METHODS:

We conducted a pilot study of patients above 18 years old diagnosed with a brain tumor who receive their care at our institution. Ten patients were enrolled to undergo a comprehensive cranial nerve and neuro-ophthalmic testing using our proprietary telemedicine software. We assessed visual acuity, visual fields, extraocular movements, facial sensitivity, facial symmetry, hearing, uvula/palatal movement, shoulder elevation, tongue deviation, and speech. Their performance on the telemedicine software to physical examination by their treating physician. All patients were given a patient satisfaction survey upon completion of the telemedicine visit.

RESULTS:

Ten patients have been enrolled so far with a mean age of 47±14.3 years old (4 males, 6 females). Diagnoses included brain metastases, pituitary adenoma, craniopharyngioma and meningiomas. Visual acuity, facial sensitivity, facial symmetry, shoulder elevation, tongue deviation were consistent with physical examination findings in all six patients. Extraocular movements were consistent in 80% of patients. Assessment of the uvula was the most challenging, comparable to physical examination in only 20% of patients. Visual fields were equivalent in 80% of patients and superior than confrontation testing in 10% of patients.

CONCLUSION:

While this is a very early experience with a new telemedicine software, we demonstrate the feasibility of performing comprehensive cranial nerve and neuro-ophthalmic testing. We provide a detailed account of the challenges encountered, the patient experience and satisfaction results.
359 The Cost of Illness of an Aneurysm Rupture: A Prospective Study to Quantity the Unseen Cost of Aneurysmal Subarachnoid Hemorrhage
Authors: Mohammadi Nicki , Spica Natalia R. , Yaeger Kurt , Chada Deeksha , Smith Colton , Reynolds Alexandra , Lay Cappi C. , Mocco J. D. , Dangayach Neha , Kellner Christopher P.
Published: March 2022

INTRODUCTION:

Subarachnoid hemorrhage (SAH) is a devastating neurological event affecting 1/10,000 adults globally with a mortality of more than 30%. SAH is financially straining for both the patient and caretaker due to its high morbidity, prolonged hospital stay, intensive treatments, and involved recovery. In this prospective study, we aim to quantify the total direct and indirect costs of SAH throughout the acute and subacute care periods.

METHODS:

Patients and their self-reported primary caregivers were prospectively followed for up to a year after the ictus hemorrhagic event, and queried monthly about expenses related to the recovery process. Additional clinical and cost information was obtained from the hospital finance department and directly from patient/caregiver follow-up interviews.

RESULTS:

Thirty-three patients were enrolled in this prospective study including 28 females (85%) and 5 males (15%) with a median (quartile range) age of 58 (47-66). Thirty-nine designated caregivers were also enrolled. The median ICU and hospital length of stay were 14 (11-19) and 19 (15-23) days, respectively. The median total cost for these patients was $135,568 ($38,082 - $644,688) and the median direct cost was $73,161 ($55,138 - $91,596) with a median expected patient payment of $114,453 ($70,772 -$204,855). The median percentage of direct costs attributed to the ICU was 40% (32-45). Patients with Medicare had smaller ranges of costs. Additionally indirect hospital costs reported were for travel related costs (hotels, ride shares, metro cards), toiletries, home modifications and medications ranging from $0 to $1000 a day.

CONCLUSION:

SAH is consistently a devastating neurological event affecting active members of society and their social networks. Its complicated course and recovery process can leave patients confined to a hospital for extended periods of time. As providers, we must investigate avenues to mitigate the costs and burdens patients and their support networks face.
373 Transependymal Cerebrospinal Fluid Flow is Etiology and Region Specific
Authors: Yang Peter H. , Almgren-Bell Alison , Dupepe Esther , Strahle Jennifer
Published: March 2022

INTRODUCTION:

Transependymal movement of cerebrospinal fluid (CSF) is a recognized imaging finding in the setting of hydrocephalus. However it is not well known which ependymal regions display transependymal flow (TEF) and which etiologies of CSF disturbances are associated with TEF. Furthermore, the association of specific TEF patterns with underlying pathology is not known.

METHODS:

We performed a cross-sectional study of 219 pediatric patients at St. Louis Children’s Hospital between 2008 and 2019 who were found to have TEF on imaging with images available for direct review. TEF pattern, degree, location, underlying pathology and other radiographic and clinical features pertaining to CSF autoregulation and intracranial pressure were noted.

RESULTS:

Average age of the cohort was 8.2 years and 45.4% were female. TEF was most commonly seen in the setting of an obstructive tumor (70.8%) and rarely in the setting of myelomeningocele (1.8%). TEF was most frequently found in the anterior aspect of the frontal horns and posterior aspect of the occipital horns of the lateral ventricles (typical TEF pattern) and this pattern was seen in 69.4%. TEF less frequently occurred across the ependyma of the third ventricle (37.4%). TEF extension to the splenium of the corpus callosum was more commonly seen in those with medulloblastoma compared to patients with pilocytic astrocytoma (P = .0149). Patients who required temporary, but not ultimately permanent, CSF diversion had a larger degree of TEF, presence of papilledema, a typical TEF pattern, and higher opening pressure. Conversely, patients who ultimately required permanent CSF diversion had a smaller degree of TEF, lack of papilledema, an atypical TEF pattern, and a lower opening pressure.

CONCLUSION:

TEF is commonly confined to the lateral ventricles (anterior aspect of the frontal horns and posterior aspect of the occipital horns) and is etiology specific. Atypical TEF patterns are associated with need for permanent CSF diversion. Finally, tumor pathology may dictate variations in TEF, suggesting a possible tumor-CSF-ependymal interaction distant from the tumor.
375 Volume-Outcome Relationships in Pediatric Neurosurgery: An Analysis of the Kids’ Inpatient Database
Authors: Brandel Michael G. , Rennert Robert , Steinberg Jeffrey , Gonda David D. , Levy Michael L.
Published: March 2022

INTRODUCTION:

Surgical volume has been established as an important determinant of patient outcomes, with progressive regionalization and subspecialization of care.

METHODS:

We identified patients 0-20 years of age who underwent neurosurgical treatment for 1 of 11 conditions in the Kids’ Inpatient Database (KID), 2003-2009: malignant brain tumor, adolescent idiopathic scoliosis (AIS), tethered cord, Chiari malformation, craniosynostosis, traumatic brain injury (TBI), traumatic spinal injury, unruptured intracranial aneurysm, hydrocephalus, peripheral nerve injury, and epilepsy. High-volume (HV) surgeons/hospitals were those in the top tertile of annual case volume. We used multivariable two-level mixed-effects logistic regression analyses to account for clustering of patients within surgeons and clustering of surgeons within hospitals.

RESULTS:

Overall, 40,973 patients met inclusion criteria. Patients were more likely to be treated by a HV surgeon if they were at a HV hospital (range, 51.4% for peripheral nerve repair to 75.6% for aneurysm) for all conditions except for spinal injury (34.8%). There was reduced risk of complications for HV surgeons in tethered cord, TBI, AIS, and aneurysm (all p<0.05). Adjusted for hospital volume, the effect of HV surgeons was maintained only for TBI (OR=0.81, p=0.026). HV hospitals accounted for 42% of the HV surgeon effect for tethered cord, whereas HV surgeons accounted for 94% of the HV hospital effect for aneurysm. Adjusted for hospital volume, HV surgeons had lower length of stay (LOS) for tethered cord (OR=0.31, p=0.010), nerve injury (OR=0.44, p=0.004), hydrocephalus (OR=0.60, p<0.001), and AIS (OR=0.48, p<0.001). HV hospitals accounted for 60% of the effect of HV surgeons on LOS in tumor, whereas HV surgeons accounted for 88% of the effect of HV hospitals in tethered cord, 62% in hydrocephalus, and 31% in aneurysm. Adjusted for hospital volume, HV surgeons had reduced adverse discharge for craniosynostosis (OR=0.12, p=0.005) and hydrocephalus (OR=0.52, p<0.001). HV surgeons accounted for 89% of the effect of HV hospitals in craniosynostosis, and 26% in hydrocephalus.

CONCLUSION:

Although surgeon and hospital volume are sometimes used interchangeably, the two may have different effects on outcomes in pediatric neurosurgery, with one at times explaining variation in the other.
379 Timing of Intra-abdominal Surgery and Ventriculoperitoneal Shunt Placement in the Pediatric Population: Risk of Shunt Infection
Authors: Harward Stephen C. , Komisarow Jordan M. , Rames Jess , Hodges Sarah E. , Rice Henry , Thompson Eric M. , Fuchs Herbert E. , Muh Carrie R. , George Timothy M. , Grant Gerald A.
Published: March 2022

INTRODUCTION:

Patients requiring placement of a ventriculoperitoneal (VP) shunt during the first year of life often have other comorbidities necessitating additional intra-abdominal surgeries during this first year. Some have suggested that the temporal proximity and sequence of these procedures may lead to a higher risk of subsequent shunt infection; however, data supporting such suggestions have proven limited and inconsistent.

METHODS:

We performed a retrospective review of all children during the first year of life who underwent both a VP shunt and an intra-abdominal procedure at a single institution between January 1, 2000 and January 1, 2018. We examined the impact of timing as well as sequence of surgeries (VP shunt first versus intra-abdominal procedure first) on shunt infection rates within 1 year of the last procedure. We additionally examined the effect of gestation age, birth weight, and placement of a prior ventricular reservoir on shunt infection.

RESULTS:

We identified 53 total patients undergoing both procedures with 16 having the intra-abdominal procedure first compared to 33 having the VP shunt first. Patients who had the intra-abdominal procedure first had a significantly higher rate of infection – 44% (7 of 16 patients) – compared to those who had the VP shunt first – 3% (1 of 33 patients). Further analysis failed to attribute this difference in shunt infection rate to differences in gestational age, birth weight, or time between the procedures.

CONCLUSION:

In our study, for patients needing both a VP shunt and a separate intra-abdominal surgery, the order of surgery greatly impacted one’s subsequent risk of VP shunt infection. These data suggest that if at all possible, the VP shunt should be performed prior to an intraabdominal procedure.
412 Outcome Forecasting in Aneurysmal Subarachnoid Hemorrhage: Comparison of a Neural Network Model With Conventional Logistic Regression
Authors: Feghali James , Sattari Shahab Aldin , Wicks Elizabeth , Gami Abhishek , Rapaport Sarah , Azad Tej D. , Yang Wuyang , Xu Risheng , Tamargo Rafael J. , Huang Judy
Published: March 2022

INTRODUCTION:

Interest in machine-learning-(ML)-based predictive modeling has led to the development of models predicting aneurysmal subarachnoid hemorrhage (aSAH) outcome, including the Nijmegen acute Subarachnoid Hemorrhage calculator (Nutshell). Generalizability of such models to external data and their performance in comparison to more established conventional logistic-regression-based models, such as the Subarachnoid-Hemorrhage-International-Trialists-(SAHIT) calculator tool, remains unclear.

METHODS:

A prospectively-maintained database of aSAH patients presenting consecutively to our institution in the 2013-2018 period was used. The web-based Nutshell (https://nutshell-tool.com/) and SAHIT (http://sahitscore.com) calculators were used to derive the risks of poor long-term (12-18 month) outcome and 30-day mortality. Discrimination and calibration were evaluated using area under the curve (AUC) and calibration plots. Literature on relevant ML models was surveyed for a synopsis.

RESULTS:

The SAHIT models outperformed the Nutshell tool in predicting long-term functional outcome (AUC: 0.786 vs. 0.689, p = 0.025) and 30-day mortality (AUC: 0.810 vs. 0.636, p < 0.001). Calibration properties were additionally more favorable for the SAHIT models. Most published aneurysm-related ML-based outcome models lack external validation and usable testing platforms. In total, 24 studies utilizing ML models were identified in our literature review, evaluating various aSAH-related and aneurysm treatment outcomes. Only two studies pursued external validation, and only five provided a testing platform for their model to be used by external researchers (e.g. scoring system, calculator, decision tree etc.).

CONCLUSION:

The Nutshell tool demonstrated limited performance upon external validation in comparison to the SAHIT models. External validation and the dissemination of testing platforms for ML models must be emphasized.
414 Flow Diversion for Middle Cerebral Artery Bifurcation Aneurysms: A Multicenter Cohort
Authors: Salem Mohamed M. , Dmytriw Adam A. , Khorasanizadeh MirHojjat , Lay Sovann Vathana , Renieri Leonardo , Sweid Ahmad , Moore Justin M. , Jabbour Pascal , Ogilvy Christopher S. , Limbucci Nicola , Cognard Christophe , Thomas Ajith J.
Published: March 2022

INTRODUCTION:

Data regarding safety and efficacy of flow diversion in treatment of middle cerebral artery (MCA) bifurcations aneurysms are scarce and limited to small single center series, with particular concern for increased risk of ischemic complications with jailing one of the M2 branches.

METHODS:

We retrospectively reviewed prospectively-maintained databases for patients harboring MCA bifurcation aneurysms who underwent flow diversion treatment in 4 US and European centers in the period from 2011-2018. The relevant clinical and radiographic data was collected from the medical records. The primary outcome was aneurysm occlusion at the last follow up with secondary outcomes of clinical status and complications.

RESULTS:

Sixty-two patients (median age 57.1 years, 66% females) harboring 62 aneurysms were included. Majority of aneurysms were unruptured (79%); 74.2% were saccular and with a mean maximal diameter of 9 mm. Last imaging follow-up was performed at a median of 16.3 months after the treatment, showing complete occlusion in 61.3%, and near complete occlusion (90-99%) in 17.7% of aneurysms. The overall rate of ischemic and hemorrhagic complications were 11.3% and 1.6% respectively. Symptomatic and permanent complications were encountered in 4.8% and 3.2% of patients respectively. Retreatment was pursued in 3.2% of the patients. Jailed branch occlusion was detected in 12.9% of cases. Last follow up mRS of 0-2 was noted in 96.8% of patients.

CONCLUSION:

Flow diversion for MCA bifurcation aneurysms is feasible with reasonable safety and efficacy profile when utilized in carefully selected aneurysms. Jailing of M2 branches is not associated with a high risk of post-procedural ischemic complications.
440 Have We Made Temporal Advancements in Optimizing Surgical Outcomes and Recovery for High Risk Spinal Deformity Patients?
Authors: Passias Peter G. , Passfall Lara , Lafage Virginie , Lafage Renaud , Line Breton G. , Vira Shaleen , Tretiakov Peter S. , Gum Jeffrey L. , Kebaish Khaled , Than Khoi D. , Mundis Gregory M. , Hostin Richard A. , Gupta Munish C. , Eastlack Robert , Anand Neel , Ames Christopher P. , Hart Robert A. , Burton Douglas C. , Schwab Frank , Shaffrey Christopher I. , Smith Justin S. , Klineberg Eric , Bess Shay ,   International Spine Study Group
Published: March 2022

INTRODUCTION:

Surgical correction of adult spinal deformity (ASD) has high rates of complication. However, patients often derive significant benefits in functional status and quality of life from surgery despite high-risk status. It has yet to be investigated whether spine surgeons are improving surgery for high risk patients and minimizing poor outcomes.

METHODS:

Included: operative ASD pts =18 yrs with pre-(BL) and 2-year (2Y) postop radiographic/HRQL data. Pts were categorized as having undergone surgery from 2009 to 2013[Early] or 2014 to 2018[Late]. High risk [HR] pts were defined as meeting =2 of the following BL criteria: 1) ++PILL or SVA by SRS-Schwab, 2) elderly [=70yrs], 3) severe frailty[Miller index], 4) high CCI [=1 SD above cohort mean], 5) three column osteotomy, and 6) fusion of >12 levels, or >7 levels for elderly pts. Differences in Smith et al. best/worst clinical outcomes, radiographic alignment targets(SRS-Schwab, age-adjusted, GAP score), and complication rates were assessed by time of surgery(Early/Late) for HR pts.

RESULTS:

725 ASD pts included (61yrs, 77%F, CCI: 1.82±1.74, levels fused 11.0±4.4). 18.5% underwent 3CO. SRS-Schwab modifiers at BL: 41.4% ++PI-LL, 30.3% ++SVA, 28.8% ++PT. 47% of pts (n=338) had surgery prior to 2014[Early], and 53% (n=387) underwent surgery in 2014 or later[Late]. Overall, 52% of pts (n=377) were deemed high risk[HR]. There was a higher proportion of HR pts in the Late group (p=0.028). In terms of individual HR criteria: Late pts were older, more likely to be ++PI-LL at BL, had higher CCI, and were less likely to undergo 3CO (all p<0.05). Analysis of HR pts by Early/Late status showed no significant differences in radiographic alignment by SRS-Schwab, age-adjusted target, or GAP score by 2Y (all p>0.05). Late/HR pts were less likely to have a poor outcome by Smith et al. definition for SRS and ODI (both p<0.01). Late/HR pts had lower rates of complication, reoperation, deep surgical infection, early PJK (before 6 months), and PJF by 2Y (p<0.05).

CONCLUSION:

Over time in our data set, spine surgeons have both increased and optimized operating on high risk patients, while minimizing the occurrence of poor clinical outcomes and reducing complication rates.
445 Lumbar Intervertebral Disc mRNA Sequencing Identifies the Regulatory Pathway in Young Adult Patients with Disc Degeneration
Authors: Moinuddin F.M. , Bhandarkar Archis R. , Onyedimma Chiduziem , Jarrah Ryan , Bydon Mohamad
Published: March 2022

INTRODUCTION:

The process of intervertebral disc degeneration disease (DDD) is thought to be an age-related phenomenon that includes inflammation and cell apoptosis leading to decreased proteoglycan synthesis with resultant disc dehydration and loss of disc height. It has been reported that 42% of young adults have DDD characterized by a signal change on MRI, it seems beneficial to examine young adults to clarify the process of DDD.

METHODS:

We performed next generation RNA sequencing on 9 nucleus pulposus (NP) of the lumbar intervertebral disc from young adults (<40 years age, n = 4) and old adults (>40 years of age, n = 5) patients. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analyses were performed to identify the biological functions of differentially expressed mRNAs.

RESULTS:

A total of 98 genes were found to be significantly upregulated in young adults NP tissue compared to old adults NP tissue. These upregulated mRNAs were primarily involved in signal peptide, collagen, and extracellular matrix organization. Among the top upregulated genes such as LGALS1, COL6A2 and PTMS may have the key regulatory functions related to early age disc degeneration. In addition, we found 346 genes were significantly downregulated in young adults NP tissue compared to old adults NP tissue. They were primarily involved in glycoprotein, membrane, and immunoglobulin-like fold.

CONCLUSION:

This investigation provides a comprehensive overview of mRNA expression in the nucleus pulposus of intervertebral disc tissue in young adult patients compare with old adult patients. By applying computational analyses to our large dataset of human clinical specimens, we have been able to identify candidate gene regulatory networks that act in early age disc degeneration.