bluuebunny/crossref_metadata_2025_split huggingface dataset:
311 A Feasibility Study for a Multicenter Phase-III Randomized Clinical Trial of Encephaloduroarteriosynagiosis Revascularization for Symptomatic Intracranial Atherosclerosis
Authors: Nisson Peyton Lubbock , Quintero-Consuegra Miguel D. , Chang Daniel , Saver Jeffrey L. , Chimowitz Marc , Gonzalez Nestor R. 
Published: March 2023

INTRODUCTION:
Stroke due to intracranial-atherosclerotic-disease (ICAD) remains a major public health concern, accounting for more than one-tenth of all ischemic-strokes in the US.

METHODS:
New data from advanced cerebral imaging and angiographic studies showed that revascularization after indirect-bypass occurs earlier than appreciated before. A pilot study of EDAS in ICAD patients demonstrated angiographic neovascularization as early as 1 month. An NINDS-funded phase-II objective-performance-criterion trial demonstrated reduction in the rate of stroke and death from 21.1% in the medical group to 9.6% in the surgical group at 2 years, passing the threshold for advancement to phase III. In collaboration with the NIH-StrokeNet, a national feasibility survey was sent to sites across the country to evaluate the feasibility of a phase-III clinical trial of EDAS in ICAD.

RESULTS:
Among 72 surveys completed by prospective sites, 90% (n = 65) indicated interest in participating and 96% of these (n = 63) had neurosurgeons and anesthesiologists with sufficient experience in EDAS and cerebrovascular disorders. The mean number of direct/indirect cerebral bypass surgeries per year completed at the prospective 40 sites was 19 (Range = 10-37). StrokeNet sites cared for a median of 42.5 patients/site/year (IQR = 25-100 patients/site/year) who met enrollment criteria. With 40 participating sites, the rate of enrollment needed for successful recruitment of 516 patients in a phase-III trial is 0.28 patients/site/month (3-4 patients/year), which is an order of magnitude less than the number of relevant cases receiving care at the sites (3.54 patients/month).

CONCLUSIONS:
EDAS is a promising technique in the management of ICAD and its performance is feasible within 40 high volume institutions. Engagement of the neurosurgical community on revitalizing a surgical form of revascularization can expand the role of neurosurgery in stroke management.
314 Radiographic Risk Factors for Intracranial Hemorrhage in Patients with Left Ventricular Assist Devices
Authors: Kanter Matthew , Hernandez Nicholas , Yu-Der Wang Andy , Sharma Vaishnavi , Riesenburger Ron I. , Kryzanski James 
Published: March 2023

INTRODUCTION:
Intracranial hemorrhage (ICH) in patients with left ventricular assist devices (LVAD) is a complication with significant morbidity and mortality. Many studies have identified demographic risk factors for ICH in LVAD patients; however, anatomic pre-disposition to ICH in these patients has not yet been investigated.

METHODS:
We reviewed 440 patients who received an LVAD at our institution. We then selected patients who received CT scans of the head for any reason near the time of LVAD placement. 288 patients (21 ICH, 278 Control) with CT scans were included in the analysis. A detailed chart review was then performed to collect data on patient demographics, radiographic findings, and complications.

RESULTS:
The incidence of ICH in our complete cohort was 8.6% (38/440). The presence of pump thrombosis (p = 0.001), driveline infection (p = 0.034), other hemorrhage (p = 0.001), or previous placement of a cardio-defibrillator (p = .003) during the period of LVAD implantation was associated with increased risk for ICH. An analysis of patient imaging revealed that the presence of a mass (p = 0.006), vascular malformation (p = 0.001), and microangiopathy (p = 0.04) was significantly associated with ICH in LVAD patients. We further validated the significance of these radiographic features using a multivariate logistic regression which showed that the presence of a mass (aOR 332.1, 95% CI: 14.7-7485.1, p < 0.001), vascular malformation (aOR 69.7, 95% CI: 1.8-2658.8, p = 0.022), and microangiopathy (aOR 6.5, 95% CI: 1.1-37.6, p = 0.035) were independently associated with ICH.

CONCLUSIONS:
Radiographic evidence of microangiopathy, intracranial mass, and vascular malformation are independent risk factors for ICH which may be identified at or before the time of LVAD implantation. We advocate that CT imaging may be used to further stratify patients at highest risk of ICH during treatment with an LVAD.
350 A Comparison of Incidental and Symptomatic Unruptured Brain Arteriovenous Malformations in Children
Authors: Lu Alex Y. , Winkler Ethan A. , Garcia Joseph , Raygor Kunal P. , Fullerton Heather , Fox Christine , Kim Helen , Auguste Kurtis Ian , Sun Peter P. , Hetts Steven , Lawton Michael T. , Abla Adib Adnan , Gupta Nalin 
Published: March 2023

INTRODUCTION:
Unruptured brain arteriovenous malformations (AVMs) may present with headaches, seizures, and/or neurologic deficits. A smaller number of cases may be discovered incidentally. These lesions remain incompletely understood due to their sparse reporting.

METHODS:
We performed a retrospective analysis of patients presenting with brain AVMs from 1998 to 2021 at the University of California, San Francisco. Inclusion criteria included age ≤18 at time of presentation with angiographically-proven unruptured AVM diagnosed postnatally.

RESULTS:
Of 76 children with unruptured AVMs, 66 (86.8%) presented with headaches, seizures, and/or neurologic deficit. Ten (13.1%) were incidentally discovered through unrelated disease workup (50%), cranial trauma (40%), or research study participation (10%). Compared to symptomatic unruptured AVMs, incidental unruptured AVMs possessed smaller mean nidus maximum diameter (2.82 ± 1.1 vs. 3.98 ± 1.52 cm, p = 0.025) and deep venous drainage proportion (20% vs. 61%, p = 0.036). They also presented at earlier ages (10 ± 5.2 vs. 13.5 ± 4 years, p = 0.043) with longer durations to first treatment (541 ± 922 vs. 196 ± 448 days, p = 0.005). During the period of observation, one patient developed recurring headaches and demonstrated AVM nidus growth. Four AVMs greater than 3 centimeters or in deep location were treated with radiosurgery. Six other AVMs were treated with surgical resection with 2 receiving preoperative embolization. Seven AVMs (70%) were obliterated on last follow-up. Postprocedural complications included 2 transient neurologic deficits following resection and 1 delayed seizure development following radiosurgery. The mean follow-up period was 5.1 ± 5.8 years without any hemorrhage episodes.

CONCLUSIONS:
A substantial proportion of pediatric patients with unruptured AVMs are discovered incidentally. With earlier presentation and more elementary angioarchitecture than symptomatic unruptured AVMs, these incidental lesions provide a snapshot into AVM natural history before symptom development or rupture.
364 Fibrous Non-Union of Odontoid Fracture: Is it Safe to Accept Non-Operative Management? A Systematic Review
Authors: Gerstl Jakob V. E. , Kilgallon John , Riesenburger Ron I. , Florman Jeffrey 
Published: March 2023

INTRODUCTION:
Non-operative management of odontoid fractures can result in solid fusion, unstable non-union and fibrous non-union. Those with fibrous non-union do not demonstrate dynamic instability on imaging but the safety of accepting this as an outcome is debatable. There are multiple reports of fibrous non-union accepted without adverse consequence however reports remain scarce and there is a lack of consensus.

METHODS:
The Pubmed and Embase databases were searched in January 2022 for terms “odontoid”, “dens”, “fracture” and “nonunion”. Outcomes were extracted and categorized according to mortality, neurologic sequelae, pain, neck disability index and satisfaction.

RESULTS:
Of a total 700 abstracts screened, 79 full texts were assessed of which 13 studies were included. A total 142 patients had a fibrous non-union, all described in observational studies. Follow-up ranged between studies ranged from 0.6 to 5.8 years. None of the 142 patients had a neurologic event. One patient had a trauma-related mortality, however causality was not exposed. The majority of studies reported good to excellent pain scores. The majority of neck disabilities reported were in the range of mild to moderate apart from one study with five patients reporting severe disability. All patients reported good or excellent satisfaction.

CONCLUSIONS:
The evidence supports it is safe to forgo surgery in carefully selected patients with non-united odontoid fractures when there is near-anatomic alignment, lack of dynamic instability on imaging, normal neurologic exam and low risk for neck injury. Further study is needed to define the full natural history of fibrous non-union of odontoid fracture.
418 Early Outcomes of the American Academy of Neurological Surgery Emerging Investigator Program in Promoting Neurosurgeon-Scientists
Authors: Srienc Anja I. , Church Sophie , Korn Stephen J. , Lonser Russell R. , Zipfel Gregory J. 
Published: March 2023

INTRODUCTION:
Neurosurgeon-scientists have unique expertise to make important contributions to medicine. However, the transition from residency/fellowship training to becoming junior faculty, with the accompanying expectation of securing NIH funding, is a vulnerable period of an academic neurosurgeon’s career. The Emerging Investigator Program (EIP) is an Academy-sponsored mentorship program to support early career neurosurgeon-scientists through their transition from training to independence.

METHODS:
An analysis of the EIP was performed using demographic data provided by the EIP coordinator (author S.C.). Qualitative feedback on the program was obtained through an informal survey sent to EIP scholars (past and present) and mentors.

RESULTS:
Thirty-four scholars have participated in the EIP– fifteen have completed the program while 19 are currently participating. Eight female scholars have been accepted into the EIP (23.5%). Fifteen scholars have a PhD (44%), and 22 have had prior grant funding as residents (65%). Of the 15 EIP scholars who completed the two-year program, 10 have thus far obtained NIH funding (67%). Scholars reported the most valuable benefits of participating in the EIP were (i) feedback on grant applications and (ii) additional mentorship from outside their home institutions. Mentors reported that predictors of success included having a strong mentorship team, institutional support, and an attitude of perseverance. Scholars and mentors indicated a willingness to maintain ongoing mentor-mentee relationships outside of the sponsored EIP mentoring sessions.

CONCLUSIONS:
Scholars and mentors have had positive perceptions of the EIP. Two thirds of the program’s alumni have obtained NIH funding, suggesting early success of the EIP. Future analyses should include a more quantitative assessment of participant outcome will be pursued once more scholars have completed the program, and more detailed diversity metrics.
427 Cognitive Function and Catastrophizing in the Adult Deformity Population: Single Center Series of 111 Patients
Authors: Scheer Justin Kemp , Lui Austin , Burke John Frederick , Jedwood Chloe , Wang Albert , Wang Elaina , Catalan Tony , Chang Diana , Belfield Bethany , Thapar Isabelle Thapar , Safaee Michael , Lau Darryl , Fury Marissa , Theologis Alekos , Clark Aaron John , Ames Christopher P. 
Published: March 2023

INTRODUCTION:
Baseline cognitive impairment (CI) in adult spinal deformity (ASD) pts is unknown and may affect how they report PROMs/experience pain. Goal of this study was to determine baseline CI prevalence and how it’s related to PROMs/pain catastrophizing.

METHODS:
Single center prospective study. PROMs included the Montreal Cognitive Assessment(MOCA), Pain Catastrophizing Scale (PainCS), back pain numerical score, Oswestry Disability Index(ODI), and Scoliosis Research Society-22 (SRS22) questionnaires. Pts were stratified by normal cognition (MOCA scores 26-30), mild CI (MOCA 18-25), moderate CI (MOCA 10-17) and Severe CI (MOCA <10). PainCS (higher = more catastrophizing) has total scor e(T,max = 52) and 3 subdomains (Rumination [R,max = 16], Magnification [M,max = 12], Helplessness [H,max = 24]). Comparisons were made between pts with normal (NORM) and any type of CI (CI) as well as correlations between MOCA and PROMS. MOCA scores were compared postop.

RESULTS:
Total 111 pts enrolled (mean age 64.1 ± 9.8 yrs, 57.5% F). Mean baseline MOCA score was 25.0±3.0 (mild CI, range 14-30), 59/111(53.1%) had mild/moderate CI. No severe CI. CI pts had significantly higher mean baseline PainCS-T, PainCS-R, and PainCS-M scores than NORM. CI pts had significantly worse baseline ODI (55.2 ± 15 vs 47.9 ± 14.4, p = 0.02) but better self-reported SRS Mental score (3.3 ± 1 vs 2.7 ± 0.8, p = 0.004) than NORM. Lower baseline MOCA scores significantly correlated with higher baseline ODI(r=-0.24,p=0.015), SRS Mental (r = -0.21, p = 0.037), current back pain (r = -0.26, p=0.006), and PainCS-R (r=-0.38, p<0.001), PainCS-M(r = -0.37, p < 0.001), PainCS-H (r = -0.27, p = 0.004), PainCS-T(r = -0.36, p < 0.001). Mean pre/postop MOCA scores were not significantly different (p > 0.05).

CONCLUSIONS:
Baseline CI is frequent in ASD pts and associated with higher baseline pain/disability and pain catastrophizing compared to ASD pts with normal cognition. The CI persists postoperatively.
462 RNA-Based Therapeutics Targeting the Oncogenic Splicing Factor TRA2β Rewire Glioblastoma Cell Transcriptomes and Inhibit Their Proliferation
Authors: Leclair Nathan , Park Sunghee , Brugiolo Mattia , Angarola Brittany , Urbanski Laura , Yurieva Marina , Anczukow Olga 
Published: March 2023

INTRODUCTION:
Glioblastomas are an aggressive brain tumor that, despite current treatment paradigms, carry a poor prognosis. Novel therapies aimed at specific glioblastoma alterations are needed. Alternative RNA splicing is a critical step in gene expression that allows a single gene to encode multiple RNA and subsequently protein isoforms. Alternative splicing becomes dysregulated in human tumors, including glioblastoma, through alterations in upstream regulatory splicing factor proteins such as TRA2β, an oncogene that enhances glioma cell proliferation. Despite these known alterations, targeting alternative splicing in glioblastomas has not been leveraged therapeutically.

METHODS:
U87MG glioblastoma cells were treated with splice-switching antisense oligonucleotides (ASOs) targeting the TRA2β transcript (ASO-1570) or non-targeting control (ASO-CTL). Cancer-relevant phenotypes, including proliferation and apoptosis, were measured using high-content imaging. Transcriptomic splicing signatures were defined using high-depth RNA-sequencing with computational tools that quantify percent splicing event inclusion (PSI) and validated using RT-PCR and western blotting.

RESULTS:
ASO-1570 treatment increased inclusion of a poison-exon in TRA2β leading to decreased coding transcripts and subsequent reductions in TRA2β protein expression compared to ASO-CTL. ASO-1570 significantly decreased cell proliferation and increased apoptosis. Mechanistically, ASO-1570 treated cells exhibited significant differences in alternatively spliced events, impacting genes involved in cancer-relevant pathways such as p53 and mTOR signaling. For example, ASO-1570 led to increased exon skipping in MDM2 leading to decreased MDM2 protein expression and increased p53 wild-type expression. ASO-1570 treatment also impacted growth of U87MG 3D-neurospheres, suggesting efficacy in advanced models that better capture in vivo conditions.

CONCLUSIONS:
Glioblastoma cells are sensitive to ASO-mediated TRA2β knockdown, which mechanistically induced transcriptome wide changes that impact cancer-related pathways. Further testing of this ASO in vivo may open novel avenues for its use as a targeted glioblastoma therapeutic.
472 Low-Field Portable Magnetic Resonance Imaging for Bedside Evaluation of Ischemic Stroke in Post-Thrombectomy Patients
Authors: Sujijantarat Nanthiya , Koo Andrew B. , Jambour Ivan , Malhotra Ajay , Crawford Anna , Mazurek Mercy , Parasuram Nethra , Chavva Isha , Sze Gordon , Renado Daniela , Antonios Joseph Paul , Elsamadicy Aladine A. , Hebert Ryan Matthew , Petersen Nils , Sheth Kevin , Matouk Charles Christian 
Published: March 2023

INTRODUCTION:
Timely brain imaging is an essential component in clinical decision-making for patients undergoing mechanical thrombectomy (MT). The requirement for controlled access suites for high-field conventional MRI (cMRI) precludes rapid access for examination. In this study, we examined the use of low-field portable MRI (pMRI) in the post-thrombectomy setting.

METHODS:
Low-field pMRI was used to obtain bedside imaging in patients who underwent MT between December 2021 to April 2022 at Yale-New Haven Hospital.All pMRI exams were conducted in the standard ferromagnetic environment of the IR suite, with clinical and research staff present. Clinical, procedural, and pMRI details were collected. Two neuroradiologists served as blinded raters and evaluated pMRIs and cMRIs independently. If cMRI was not available for comparison, a post-thrombectomy CT was used.

RESULTS:
A total of 18 patients (61% females, median age 77 years-old [IQR 70-84]) underwent pMRIs in the IR suite after MT. MT was performed with a median access to revascularization time of 15 minutes [IQR 8-19], and with a TICI score of 2B and above in all patients. The median pMRI examination time was 30 minutes [IQR 13-32]. Thirteen patients (72.2%) had cMRI within 72 hours post-thrombectomy, while 4 who did not have cMRI (80%) underwent CT. Blinded raters correctly identified the presence of stroke on pMRI in all cases. Intracranial hemorrhage was identified on pMRI in 33.3% of the cases. The median infarct volume was 5.7 cc [IQR 3.83-15.43] on pMRI and 4.37 cc [IQR 0.66-16.5] on cMRI or post-thrombectomy CT. There were no adverse events related to the examination.

CONCLUSIONS:
The use of low-field pMRI is feasible in a post-thrombectomy setting and can enable timely identification of ischemic changes at bedside. Low-field pMRI may be helpful in acquiring time-sensitive brain imaging which may impact clinical decision-making post-thrombectomy.
481 Troubleshooting the Bypass: Intraoperative Management of Initially Failed Anastomosis in Cerebral Extracranial – Intracranial Direct Revascularization Surgery
Authors: Doron Omer , Langer David J. , Nossek Erez Zeev 
Published: March 2023

INTRODUCTION:
Direct cerebral revascularization is considered one the most technically challenging operations in neurosurgery. Technical errors are often not identified during the completion of the anastomosis. Initial assessment and management at this moment can determine the success of the entire case, making re-circulation one of the most stressful moments in the procedure.

METHODS:
A retrospective analysis of direct bypass cases based on operative reports and available videos, were studied in detai. A case was defined as an “initially failed bypass”, irrespective of its final result, if after removal of the temporary clips, the bypass was not patent, or significant leak was encountered.

RESULTS:
138 cases were included (109 being STA-MCA) done for flow replacement (n = 49), or for flow augmentation (n = 89). 45 initially failed anastomosis, out of which 37 were the result of a technical error encounterd. Causes were clot(n = 10), vessel kinking(n = 5), spasm(n = 6), inappropriate donor(n = 3) or recipient(n = 2), competitive flow(n = 6) or a leak(n = 5). 31/37 cases were troubleshooted successfully resulting in a working bypass. Rescue maneuvers included: Partial re-opening of the suture line and irrigation for clot, graft repositioning for kinking, papaverine-vessel massage for spasm, and partial vessel cut at the donor site for anastomosis inspection. In “local” lack of demand, a new anastomosis was done by the same donor. 30-days follow-up showed similar rates of patency between successfully troubleshooted patients and the rest of the patients (82% vs 85%, p = 0.35).

CONCLUSIONS:
A comprehensive approach detailing technical “corrections”, describing maneuvers and the sequence of actions done in order to “revive” the bypass, as well as their prevalence, was not previously well described. In this study we present 3 of initial failure types: a leak, acute occlusion or delayed occlusion, presenting an algorithm for intra-operative management in these cases.
487 Clinical Outcomes of Decompressive Spine Surgery for Painless Cervical Myelopathy: An Analysis of the Michigan Spine Surgery Improvement Collaborative (MSSIC) Registry
Authors: Deshpande Nachiket , Fadel Hassan Ali , Schultz Lonni , Abdulhak Muwaffak , Chang Victor W. , Schwalb Jason M. 
Published: March 2023

INTRODUCTION:
Cervical myelopathy (CM) is the occurrence of neurologic dysfunction secondary to any etiology that results in direct cervical spinal cord compression. Although axial neck pain and radicular arm pain are common presenting features in CM, some patients present atypically with myelopathic symptoms in the absence of neck or arm pain. To date, little is known regarding the outcomes of surgical decompression in these patients.

METHODS:
This is a retrospective study of prospectively collected data from the Michigan Spine Surgery Improvement Collaborative (MSSIC) registry. A total of 340 patients undergoing spine surgery for painless CM were analyzed. Surgical and patient reported outcomes, including minimal clinically important difference (MCID) in modified Japanese Orthopedic Association (mJOA) scores and Patient-Reported Outcomes Measurement Information System Physical Function (PROMIS PF) scores, were assessed at 90 days, 1 year, and 2 years postoperatively.

RESULTS:
At 90 days following surgery, a MCID in PROMIS PF and mJOA scores was seen in 42% and 36% of patients, respectively. The proportion of patients with MCID in mJOA scores remained stable at 1- and 2-year follow-up, while the percentage of patients with MCID in PROMIS PF scores decreased to 22% at two years post-operatively. When stratifying by pre-operative CM severity, patient reported outcomes and surgical complications did not significantly vary. Importantly, patient satisfaction remained above 80% at 90 days, 1 year, and 2 years after surgery.

CONCLUSIONS:
Following surgical intervention, clinically significant improvement was seen in a modest number of patients. The high degree of sustained patient satisfaction suggests that our measured outcomes may not accurately capture the degree of improvement that is important to patients, or it may represent happiness from not experiencing further functional decline.