bluuebunny/crossref_metadata_2025_split huggingface dataset:
272 Integrative Genomics Implicates Primary Impact on Cortical Development in Spina Bifida
Authors: Phan Duy , Shaffrey Mark Edwin , Park Min S. 
Published: March 2024

INTRODUCTION:
Spina bifida is one of the most common malformation of the central nervous system that is associated with poor neurodevelopmental outcomes. Altered neurodevelopment in spina bifida has been attributed to venting of CSF through the neural tube defect. Despite correction of the spinal defect, some patients still develop hydrocephalus with poor neurodevelopmental outcomes, suggesting incomplete understanding of disease pathogenesis. Recent human genetic efforts have identified candidate genes that confer spina bifida risk, however, the mechanisms linking gene mutations to altered neurodevelopment remain poorly understood.

METHODS:
We curated a list of 439 genes that confer risk to spina bifida from a whole-genome sequencing study of 310 individuals. We then mapped the spatiotemporal and cell-type specific expression of these risk genes onto bulk and single-cell RNA sequencing data of normally developing human brains covering the entire lifespan of human development.

RESULTS:
We found that spina bifida risk genes are enriched at post-conception weeks 5-6 and 25-38 in the developing human brain. After birth, spina bifida risk genes are enriched at postnatal months 6-10 and then after 60 years of age. At the cell type level, spina bifida risk genes are enriched in proliferative neuroprogenitor cells and microglia in the prenatal human cortex.

CONCLUSIONS:
Our analyses show that spina bifida risk genes are expressed in the developing human brain, suggesting a primary impact on brain development that is independent from the open caudal end of the neural tube defect. The finding that spina bifida risk genes continue to be expressed postnatally suggests a window for therapeutic intervention to optimize neurodevelopmental outcomes after birth in at least a subset of patients.
290 A Rib-Sparing Unilateral Transpedicular Thoracic Corpectomy Using the Ultrasonic Bone Scalpel: A Novel Technique and Pictorial Guide
Authors: Foster Chase H. , Mehta Aadit Piyush , Floyd Calvin , Herzig David Warren , Levine Zachary , Rhee Jay W. 
Published: March 2024

INTRODUCTION:
Posterior thoracic corpectomies typically require removal of the costotransverse articulation and some amount of the adjoining rib, an accompaniment that has been shown to result in significant post-operative morbidity. There are several well-described approaches to pathology of the thoracic spine, each with advantages, disadvantages, and inherent limitations.

METHODS:
The technique is demonstrated step-by-step in a videographic pictorial description of the procedure performed on both a molded plastic spine model and on a cadaveric specimen. A retrospective chart review was conducted on patients having undergone this thoracic corpectomy technique since its implementation at the senior author’s institution. Patient data, operative metrics, and outcomes were collected and analyzed.

RESULTS:
A total of 36 corpectomies were performed on 32 patients (mean age = 63 years). There were oncological (n = 22, 69%), degenerative/traumatic (n = 7, 22%), and infection (n = 3, 9%) indications. EBL averaged 853 cc for 30/32 cases. Operative time averaged 177.83 minutes. Length of stay averaged 6.47 days. One clinically inconsequential iatrogenic durotomy occurred. One patient had a surgical site infection three weeks later that required wound washout without hardware revision.

CONCLUSIONS:
Rib resection correlates with significant post-operative pain. This thoracic corpectomy technique mitigates morbidity by avoiding manipulation, destabilization, or resection of the rib, potentially permitting faster recovery and discharge. The technique is dependent on the UBS as it expediently creates a tailored window for an expandable corpectomy cage. A rib-sparing thoracic corpectomy can be effectively, efficiently, and safely performed using a combination of the UBS and an expandable cage during a single stage posterior-only unilateral transpedicular approach with which most spine surgeons are familiar.
295 High Volume Centers Provide Superior Value of Care in the Surgical Treatment of Malignant Brain Tumor
Authors: Vazquez Sima , Dominguez Jose Fernando , Spirollari Eris , Soldozy Sauson , Ivan Michael E. , Merenzon Martin Andres , Hanft Simon Jeremy , Komotar Ricardo Jorge 
Published: March 2024

INTRODUCTION:
Improved outcomes in surgical patients have been associated with increasing volume of cases. This has led to the development of centers that facilitate care for a specific patient population.

METHODS:
The 2016-2020 National Inpatient Sample (NIS) was queried for patients undergoing resection of malignant brain tumors. Teaching hospitals with high case load (greater than two standrad deviations above the mean, or >140 cases) were categorized as high-volume centers (HVC). Value of care was computed by adding one point for each of the following variables: lower length of stay, lower total charges, discharge to home, and lack of major comorbidity or complication, as defined per DRG codes.

RESULTS:
A total of 118,390 patients underwent resection of malignant brain tumors in 3,009 hospitals. HVC criteria was met by 91 (3%) hospitals, which represented 20,230 (17.1%) of total cases. The Mid-Atlantic and South Atlantic regions had the highest percentage of cases (22.7% and 20.2%, respectively) and number of HVC (21 and 17, respectively). Value of care was higher at HVC (OR = 1.35 95%CI 1.31-1.39 p < 0.01). After controlling for baseline risk factors and high risk admissions, HVC was associated with decreased complications of intracranial hemorrhage, deep venous thrombosis, aspiration pneumonitis, acute kidney injury, and external ventricular drain requirement (p < 0.01 for all). HVC was also associated with decreased length of stay and increased rate of discharge to home (p < 0.01 for both).

CONCLUSIONS:
Patients undergoing craniotomy for malignant brain neoplasms have superior outcomes in HVC. Trends of centralization are likely a reflection of the benefits of multidisciplinary treatment for these patients. Improvement of access to care at these institutions may improve the efficiency of the delivery of care for these patients.
297 Impact of Navigated Intraoperative Ultrasound on Brain Shift and Gross Tumor Resection
Authors: West Timothy , Mazurek Mercy H. , Razak Shahaan S. , Gal Zsombor Tamas , Perez Nicole , Burrows Akeive , Choi Bryan D. , Nahed Brian V. 
Published: March 2024

INTRODUCTION:
Intraoperative imaging and neuronavigation aid in achieving maximum tumor resection. However, tissue removal during surgery can cause brain shift, which alters the relative anatomy and “de-calibrates” the standard approaches. While intraoperative MRI (iMRI) is the gold-standard to correct for brain shift, it is expensive, time-consuming, and logistically difficult. As an alternative, we investigated an approach which combines intraoperative ultrasound (ioUS) technology with preoperative imaging to allow for real-time compensation of brain shift and assessment of extent of resection (EOR).

METHODS:
We prospectively enrolled patients undergoing neurosurgical tumor resection at Massachusetts General Hospital beginning April 2023. Patients were registered with Brainlab Ultrasound Navigation prior to surgery. ioUS sweeps were acquired before cortex incision, mid-resection, and post-resection with bkActiv and fused to preoperative MRIs. Four points around the tumor were longitudinally tracked to assess brain shift. Data included sweep duration, image processing speed, extent of brain shift as determined by intraoperative markers, and EOR assessed from the ioUS compared with postoperative MRIs.

RESULTS:
Seven patients were enrolled (average age 62 ± 15, 75% male) with frontal (n = 5), temporal (n = 1), and occipital (n = 1) gliomas (n = 4) and metastases (n = 3). All patients exhibiting total resection as determined by ioUS also demonstrated total resection on post-operative MRI, evaluated independently by a neuroradiologist. The average time of scan and image processing (n = 19) was 5.7 ± 1.9 and 27.8 ± 6.5 seconds respectively.

CONCLUSIONS:
Navigated ioUS offers accurate and efficient assessment of EOR during surgery for tumor resections. Furthermore, when brain shift is detected, navigated ioUS can allow for compensation and continued utilization of navigation via the acquisition of a brand new, navigable, intraoperatively acquired dataset.
300 Intracranial Tumors Hijack the Meningeal Venolymphatic Network Through VEGFR-2 Signaling
Authors: Ampie Leonel , McGavern D. 
Published: March 2024

INTRODUCTION:
Glioblastoma and other intracranial neoplasms have been associated with breakdown of the blood brain barrier. Other protective CNS barriers have sparsely been studied in brain tumors. Here, we identify the ability of intracranial neoplasms to hijack the meningeal venolymphatic network, which is driven through VEGFR-2/VEGF-A signaling.

METHODS:
C57BL/6J mice were stereotactically injected with syngeneic SB28 (glioblastoma) cell lines. Mice were treated with either isotype control or a VEGFR-2 inhibitor. Two-photon microscopy was used to visualize vascular cytoarchitecture and dynamics in vivo. Meningeal whole mounts, brains and spleens were also collected and analyzed by confocal microscopy and high parameter flow cytometry. Human dura mater from glioblastoma patients underwent multiplex immunohistochemistry to confirm the translatability of our findings.

RESULTS:
Our imaging studies revealed that glioblastomas can generate an extensive de novo network of meningeal blood vessels and lymphatics both in mice and humans. Lymphatic vessels were often observed developing in parallel to the newly formed vasculature. Intravital two-photon microscopy further revealed that the peritumoral vascular bed in the meninges of mice was leaky, dysfunctional, and generated a hypoxic microenvironment. Importantly, inhibition of VEGFR signaling impeded formation of this faulty venolymphatic network, which slowed tumor growth, reduced peritumoral hypoxia, enhanced immune infiltration, and increased survival.

CONCLUSIONS:
Our results demonstrate that glioblastomas can invade the meninges and hijack the venolymphatic network through VEGFR-2 and PECAM-1 signaling. While VEGFR-2 is associated with angiogenesis, our data suggest that it may also have an important role in regulating the simultaneous development of de novo meningeal venous and lymphatic drainage during glioblastoma.
303 Long-Term Volumetric Analysis of Non-functioning Pituitary Microadenomas: An International, Multi-center Cohort Study
Authors: Kilgallon John , Sarkar Sauradeep , Omara Chady , Sajed Sulaiman , Bakker Leontine , Biermasz Nienke , Van Furth Wouter Ralph , Verstegen Marco , Lobatto Daniel , Drexler Richard , Flitsch Jörg , Ricklefs Franz Lennard , Ryba Alice , Guaraldi Federica , Smith Timothy R. , Min Le 
Published: March 2024

INTRODUCTION:
The incidental finding of pituitary microadenomas (PmAs) is increasingly common due to the widespread use of MRI. To date, no comprehensive volumetric analyses of PmAs growth patterns have been conducted. A greater understanding of how these lesions progress could influence an array of management strategies, including frequency of imaging and the use of surgical versus conservative medical intervention.

METHODS:
Patients who underwent = 2 pituitary MRIs for suspected PmAs were identified retrospectively across 4 referral centers worldwide. Patient demographics, presenting symptoms, clinical variables, MRIs, and treatment course were collected and analyzed.

RESULTS:
A total of 447 patients (Male = 126; 28.2%) referred to the 4 centers from 2003 to 2022 were identified. Median age at first MRI was 43 years [IQR 32–54]. Median number of MRIs per patient was 3 [IQR 2–5] and median follow-up time was 55 months [IQR 29–100]. 300 PmAs (67.1%) were solid, 102 (22.8%) were cystic, 47 (10.5%) were uncertain, and 24 (5.4%) were mixed. At baseline, median suspected tumor volume was 45 mm3 [15–103]. 77 patients (17.2%) presented with subclinical hyperpituitarism, most often hyperprolactinemia, while 67 (15.0%) experienced hypopituitarism such as hypogonadism, hypothyroidism, and growth hormone deficiency. During follow-up, new onset hyperpituitarism was detected in 20 patients (4.5%) along with hypopituitarism in 9 (2.0%). During the study period, 225 patients (50.3%) had no change in suspected PmA growth, 144 (32.2%) had a decreased size, and 101 (22.6%) had an increased size. 80 patients (17.9%) received medical therapy and 48 (10.7%) underwent transsphenoidal surgery.

CONCLUSIONS:
With the forthcoming volumetric analysis, we hope to gain further insights into predictors of long-term volumetric evolution of PmAs to improve patient management.
332 Descriptive Analysis of State and Federal Malpractice Litigation in the United States Related to Neuroendovascular Procedures
Authors: Amjadi Nazaneen , Desai Sohum 
Published: March 2024

INTRODUCTION:
Medical malpractice interests the medical community at large. While previous neurosurgical review articles have analyzed malpractice in the context of spinal surgery, few have reviewed malpractice data surrounding neurovascular procedures as a whole.

METHODS:
In this retrospective review Google Scholar Case Law, Casetext and Westlaw legal databases were searched for verdict and settlement reports pertaining to neurovascular procedures from 1984 to 2023. Data were collected regarding type of procedure, patient age and gender, defendant specialty, outcome, award, and alleged cause of malpractice. Search terms included “arteriovenous malformation,” “brain aneurysm,” “aneurysm coiling,” “subarachnoid hemorrhage,” “large vessel occlusion,” “mechanical thrombectomy,” “cerebral angiography,” “carotid angioplasty and stenting,” and “carotid stenosis.” Initial search produced 212 cases, after which exclusion criteria were applied to eliminate duplicates and cases unrelated to neurovascular surgery/diagnoses or malpractice, yielding 27 cases total.

RESULTS:
The verdict favored the defendant physician(s) individually or represented by a healthcare entity in 8 of the 27 cases selected for analysis. Of 19 cases with verdicts in favor of the plaintiff, settlement values ranged from $30,000 to $15.65 million. In settlement cases, the most commonly involved procedures included AVM embolization followed by aneurysm coiling. Amongst cases where interventionist was the defendant, the most common specialty was neurointerventional radiology, followed by neurosurgery. Failure to diagnose was the most cited alleged malpractice cause (51.8%) amongst all cases, regardless of verdict.

CONCLUSIONS:
Neurovascular emergencies are often addressed by a team of medical specialists including endovascular neurosurgeons, interventional neuroradiologists, and interventional neurologists. In this review, malpractice claims related to neurovascular emergencies most likely to result in plaintiff award were related to failure to diagnose, and interventional neuroradiologists appear to be at greater risk for alleged malpractice.
385 Genomic Alterations Associated With Postoperative Nodular Leptomeningeal Disease After Resection of Brain Metastases
Authors: Morshed Ramin , Cummins Daniel Dighton , Nguyen Minh P. , Saggi Satvir , Vasudevan Harish , Braunstein Steve , Goldschmidt Ezequiel , Chang Edward F. , McDermott Michael William , Berger Mitchel S. , Theodosopoulos Philip V. , Daras Mariza , Hervey-Jumper Shawn L. , Aghi Manish Kumar 
Published: March 2024

INTRODUCTION:
The relationship between brain metastasis resection and risk of nodular leptomeningeal disease (nLMD) is unclear. Prior studies have not explored genomic alterations associated with postoperative nLMD.

METHODS:
A retrospective, single-center study was conducted with patients who underwent resection of a BM with available clinical and genomic data available. Postoperative nLMD was the primary endpoint of interest. Targeted next-generation sequencing of over 500 oncogenes using a CLIA certified assay was performed in brain metastases. Cox proportional hazards analyses were performed to identify clinical features and genomic alterations associated with nLMD.

RESULTS:
One hundred and one patients composed the cohort with tumors originating from multiple cancer types. There were 15 cases of nLMD (14.9% of the cohort) with a median time from surgery to nLMD diagnosis of 8.2 months. Two supervised machine learning algorithms consistently identified CDKN2A/B co-deletion and ERBB2 amplification as the top predictors associated with postoperative nLMD across all cancer types. In a multivariate Cox proportional hazard analysis including clinical factors and genomic alterations observed in the cohort, tumor volume (HR 8.8, 95% CI 1.1-69, p = 0.04), CDKN2A/B co-deletion (HR 5.3, 95% CI 1.7-16.9, p = 0.004), and ERBB2 amplification (HR 3.9, 95% CI 1.1-14.4, p = 0.04) were associated with decreased time to postoperative nLMD.

CONCLUSIONS:
In addition to increased resected tumor volume, ERBB2 amplification and CDKN2A/B deletion were independently associated with an increased risk of postoperative nLMD across multiple cancer types. Additional work is needed to determine if targeted therapy decreases this risk in the postoperative setting.
414 Exploration and Validation of CSF miRNAs as Predictors of Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage: A Prospective Clinical Study
Authors: Blackburn Spiros L. , Ali Shafeeque Mohammed , Mcbride Devin , Zeineddine Hussein A , Thankamanipandit Peeyush 
Published: March 2024

INTRODUCTION:
Approximately one-third of the patients who survive Aneurysmal Subrachnoid Hemorrhage (aSAH) have delayed cerebral ischemia (DCI) which contributes to poor clinical outcome.

METHODS:
A prospectively maintained clinical database was utilized under IRB approval for determination of clinical DCI and collection of biological samples. CSF samples were collected at 2-time points (<24 hours and 72 hours) post-aSAH from patients treated with external ventricular drainage. miRNAs were extracted from exosomes isolated from the CSF. In the first group of patients (exploratory phase), a CSF panel containing 84 miRNAs was analyzed using quantitative real-time PCR as an exploratory phase. Using the findings from the exploratory phase, we subsequently validated 26miRNAs in a second group of patients.

RESULTS:
We found three miRNAs i.e., miR-150-5p (p=0.02), miR-140-3p (p=0.03), and miR-26b-5p (p=0.01) were significantly upregulated in 72 vs 24 hours in patients that developed DCI. Moreover, we observed miR-451a (p=<0.0001) and miR-106a-5p (p=0.0001) were upregulated in No DCI at 72 hours.

CONCLUSIONS:
Our study identifies CSF exosomal miRNAs that could be crucial in progressing aSAH to DCI, and another set of miRNAs that possibly helps in aiding protection being entered into DCI. These miRNAs could be considered as potential biomarkers for DCI progression and prevention. Specifically miR-451a and miR-106a-5p may provide a protective role by reducing inflammation mediated by Matrix Metalloproteinases genes, thus crucial in the prevention of DCI. Further validation is important in additional patient cohorts.
415 Cryopreserved Human Umbilical Cord in the Treatment of Pediatric Tethered Cord Syndrome
Authors: Kiehna Erin Nicole 
Published: March 2024

INTRODUCTION:
Tethered cord syndrome (TCS) is characterized by neurological, gastrointestinal/genitourinary, and musculoskeletal dysfunction attributable to spinal cord traction. It is estimated that 20-50% of children with open and closed neural tube defects repaired after birth will require surgery to detether the spinal cord. The cryopreserved human umbilical cord (HUC) patch has regenerative, anti-inflammatory, and anti-scarring properties. In animal models, when HUC is used as a meningeal patch it allows regeneration of the arachnoid layer, prevents spinal cord tethering, and improves spinal cord function after in utero spina bifida repair. We hypothesized that this would benefit pediatric patients requiring detethering.

METHODS:
Serial patients with clinical and radiographic evidence of a tethered cord were enrolled following informed consent. At the time of surgery they underwent spinal cord detethering with neuromonitoring. At the time of closure a HUC graft (Clarix 1k) was placed as a dural underlay, the dura was closed primarily, and a second graft was placed as a dural overlay and sealed with tissue sealant. Serial neurologic assessments and urologic assessments were obtained. MRIs are performed annually or as indicated clinically.

RESULTS:
Four patients have been detethered with use of HUC as a dural underlay and overlay (2 lipomyelomeningocele, 1 lipoma/diastematomyelia, 1 tethered cord). One patient remains neurointact, with resolution of mild neurogenic bladder. Another patient has gained sensation of lower extremities, sensation to catheterization, with resolution of neurogenic bowel and bladder. One has gained sensation to catheterization, with resolution of neurogenic bowel and bladder. The fourth patient is stable.

CONCLUSIONS:
Early use of HUC as a dural underlay and overlay during closure for tethered cord surgery shows promise in improving spinal cord function in pediatric patients.
448 Motor Control of Bladder Function by Nerve Transfer
Authors: Johnston Benjamin , Brown Justin M. , De Elise , Ruggieri Michael , Lemos Nucelio , McGovern Francis 
Published: March 2024

INTRODUCTION:
A normal detrusor muscle is activated by parasympathetic efferents that release acetylcholine to muscarinic receptors to contract and expel urine. Through canine work by our group, the scientific underpinning of a somatic nerve transfer to a visceral target (hybrid synapse) was established. We present the scientific basis of this hybrid nerve transfer and report the first-in-human functional outcome.

METHODS:
Our patient presented with deteriorating bladder function over 1 year and underwent en bloc resection of a sacral chondrosarcoma in December 2020. The sacral roots from S1 caudally were divided – resulting in loss of bowel and bladder function. Urodynamics demonstrated an acontractile bladder (0 cm H20). In May 2021 bilateral obturator nerve transfers to the vesical branches (to bladder) of the inferior hypogastric plexus (6 months after surgery). Patient bladder function and pelvic visceral sensation were followed with serial urodynamic studies.

RESULTS:
The patient was asked to adduct the thighs and relax the abdomen to initiate a detrusor (bladder) contraction. This provided definitive activation of the nerve transfer in November 2022 (1.5 years after transfer), which was confirmed in January 2023 (∼20 cm H20). Concomitantly, the filling volume at which “full bladder” was perceived appeared at 6 months and progressed until detected within normal range of bladder volumes.

CONCLUSIONS:
This is a first-in-human nerve transfer that has clear evidence of visceral sensation recovery (need to void) at normal volumes, and functional detrusor contraction. While bladder pressures produced were not within normal range, we expect transfers earlier after loss of function (e.g. within 6 months instead of 18) will result in greater functional gains.