bluuebunny/crossref_metadata_2025_split huggingface dataset:
172 No Difference in Reoperation Rates for Adjacent Segment Disease (Operative ASD) in Posterior Cervical Fusions Stopping at C7 Versus T1/T2: A Cohort of 875 Patients
Authors: Guppy Kern H. , Brara Harsimran S. , Royse Kathryn E. , Fennessy Jacob , Norheim Elizabeth , Harris Jessica 
Published: March 2022

INTRODUCTION:
The biomechanics at of the cervicothoracic junction (CTJ) have shown that adjacent segment disease (ASD) can occur more frequently if fusions are stopped at C7 although there is varying clinical evidence to support this belief.

METHODS:
A retrospective cohort study from the Kaiser Permanente Spine Registry was completed on adult patients (=18 years old) with the diagnosis of cervical degenerative disc disease, cervical trauma, or cervical deformity who underwent primary PCFs stopping at -C7 or -T1/T2. Reoperation for adjacent segment disease (operative ASD) was the primary outcome and patients were followed until operative ASD, membership termination, death, or 03/31/2020. Time-dependent crude and adjusted, multivariable Cox-Proportional Hazards models were used to evaluate operative ASD rates with adjustment for covariates or risk change estimates more than 10%.

RESULTS:
The cohort consisted of 875 patients with PCFs (between C3 to T1/T2) stopping at either -C7 (n = 470) or -T1/T2 (n = 405) with average follow-up of 4.6 (±3.3) years and average time to operative ASD of 2.7 (±2.8) years. Crude overall incidence rates for stopping at -C7 (2.12% (1.02%-3.86%)) and -T1/T2 (2.48% (1.25%-4.40%)) were comparable with no statistical difference in risk (adjHR = 1.47, 95% CI = 0.61-3.53, p = 0.39). Additionally, we observed no differences in the probability of operative ASD in time-dependent models accounting for a competing risk of membership termination (Grey’s Test p = 0.448).

CONCLUSION:
In our cohort of 875 patients with PCFs ranging from C3 to T1/T2 stopping at -C7 or -T1/T2, with an average follow-up of >4 years, we found no statistical difference in reoperation rates for adjacent segment disease (operative ASD). This is one of the largest series of patients in the literature on reoperation rates for adjacent segment disease in PCFs stopping at -C7 versus -T1/T2.
173 Hydrogel Matrix Human Stem Cell Based Nucleus Pulposus Intervertebral Disc Regeneration
Authors: Perez-Cruet Mick J. , Chaudhry Rasul , Chieng Lee O. , McKee Christina , Rapp Aaron 
Published: March 2022

INTRODUCTION:
Degenerative disc disease (DDD) is one of the major causes of chronic debilitating low back pain. DDD is characterized by changes in cell populations that result in loss of extracellular matrix (ECM) water holding capacity of the nucleus pulposus. DDD can lead to translation of physiologic loads from the anterior 2/3 to the posterior 1/3 of the spinal column resulting in stress placed on the facets and ligamentum flavum resulting in hypertrophy and canal stenosis. Novel stem cell regenerative therapies could restore the anterior column load via nucleus pulposus regeneration.

METHODS:
A hydrogel scaffold was created composed of self-assembling polyethylene glycol (PEG) functionalized with acrylate and thiol end groups. The scaffold was impregnated with nucleus pulposus (NP) cells differentiated from human umbilical cord mesenchymal stem cells (MSCs). Impregnated NP-scaffolds were then implanted into an ex vivo rabbit model of DDD and the viability and function of NP cells analyzed.

RESULTS:
The NP-scaffolds limited leakage and retained the cells in the NP region of the degenerated disc. Both the NP-scaffold and disc environment promoted differentiation of the MSCs into cells types capable of producing the ECM including sulfated glycoaminoglycans at levels higher than MSCs injected into the intervertebral disc. NP-scaffold cells also expressed chrondrogenic markers like SOX9, COL2 and ACAN at higher levels as well as NP markers FOXF1, K19, and Vimentin determined by real-time polymerase chain reaction (PCR) and immunostaining.

CONCLUSION:
This study demonstrated that a hydrogen scaffold impregnated with NP cells was much more effective at disc regeneration than NP cells alone and can lead to novel therapies for treating DDD.
177 Impact of Socioeconomics on Loss to Follow-up Following Emergent Surgery for Acute Subdural Hematoma
Authors: Guidry Bradley , Tang Alan R. , Thomas Harrison , Sermarini Anthony , Dambrino Robert J. , Yengo-Kahn Aaron M. , Chambless Lola B. , Morone Peter J. , Chotai Silky 
Published: March 2022

INTRODUCTION:
Loss to follow-up (LTF) represents an obstacle in the post-surgical management of patients following acute subdural hematoma (aSDH) evacuation. Identifying the factors associated with LTF is required to improve patient care. We sought to examine potential factors with an emphasis on socioeconomic status (SES).

METHODS:
A retrospective analysis of patients treated surgically for aSDH from 2009-2019 at a level 1 regional trauma center was conducted. The primary outcome was LTF, defined as being scheduled but not receiving any follow-up care post-discharge. The main exposure was Area Deprivation Index (ADI), a neighborhood level composite of education, employment, housing quality, and poverty; this was used to measure SES with higher ADI corresponding to lower SES. Additional candidate factors were identified in the literature and through univariate comparisons of group characteristics. To reduce the number of variables, principal components analysis (PCA) was used; the first six principal components (PCs) contained 82% of the total variance. Multivariable logistic regression was performed to identify the PCs associated with LTF.

RESULTS:
Of the 172 patients included in the study, 36 patients were LTF (21%). The predominant PCs were as follows: increasing age, craniotomy instead of craniectomy, and decreased LOS in PC1; ADI and distance to hospital in PC2; unfavorable discharge mRS and non-home disposition in PC3; uninsured/Medicaid status and increased LOS in PC4; number of comorbidities in PC5; and transfer from OSH and use of craniectomy instead of craniotomy for PC6. In multivariable analysis for LTF, greater ADI and distance to hospital via PC2 (P = 0.009) and uninsured/Medicaid status and increased LOS via PC4 (P = 0.009) were associated with increased odds of LTF.

CONCLUSION:
Socioeconomic factors including increased neighborhood disadvantage, increased distance to hospital and uninsured/Medicaid status impact LTF following emergent surgery for aSDH. These patients with limited resources are at increased risk of losing continuity of care. The health care system must direct efforts to reduce healthcare disparity in these high-risk population.
179 Clinical Outcomes From a Single-Site Phase I Study of Neural Stem Cell Transplantation for Chronic Spinal Cord Injury
Authors: Martin Joel , Curtis Erik , Cleary Daniel , Mendoza Michelle , Jamieson Catriona , Marsala Martin , Ciacci Joseph D. 
Published: March 2022

INTRODUCTION:
We previously reported safe implantation and improvement in motor and sensory scores using neural stem cell line (NSC) NSI-566 in chronic thoracic complete spinal cord injury (SCI) patients.

METHODS:
A total of four subjects received NSI-566 spinal cord implantation. All subjects tolerated the procedure well with no serious adverse events in the immediate post-procedure period. Prospective data have been collected including ISNCSCI scores, functional and pain surveys, SCIM scores, electromyography (EMG), Brain Motor Control Assessment (BMCA), and serial MRI.

RESULTS:
Two patients experienced improvements in neurological level of injury (NLI), motor score, and sensory score. BMCA showed newly developed muscle responsiveness in lower limbs to reinforcement maneuvers in one patient. Three subjects experienced new EMG activity in lower muscle groups. Two patients had overall decreased pain scores post-operatively, which included both discomfort and allodynia in the transition zone, surgical site pain, and neuropathic and nociceptive pain elsewhere. MR imaging showed no radiographical evidence of immediate or delayed complications after the stem cell injections.

CONCLUSION:
Our current clinical data demonstrate that spinal grafting of the human NSI-566 cell line in chronic spinal trauma patients is safe with no detectable side effects identified at 60 months after cell delivery. Despite the small sample size, the key strengths of the study are the extensive follow-up period and the timeline of treatment. Like other Phase I studies, this study was intended to provide proof of safety and tolerability and proof of concept data that will justify the next cohort.
181 Frameless Neuronavigation With Computer Vision and Real Time Tracking for Bedside External Ventricular Drain Placement: A Cadaveric Study
Authors: Robertson Faith C. , Sha Raahil , Amich Jose , Lee Benjamin , Lal Avinash , Calvachi Paola , Wu Kyle , Gormley William , Weaver James , Tokuda Junichi 
Published: March 2022

INTRODUCTION:
A major obstacle to improving ventriculostomy safety and accuracy with image guidance technologies is the lack of a rapidly deployable, real-time registration and tracking system for a moving patient.

METHODS:
Computer vision technology was used to develop an algorithm for near continuous, automatic, and marker-less image registration. The program fuses a subject’s pre-procedure CT scan to live 3D camera images (Snap-Surface), and movement is incorporated by artificial intelligence driven recalibration (Real-Track). Surface registration error (SRE) and target registration error (TRE) were calculated for five cadaver heads that underwent serial movements (fast and slow velocity roll, pitch, and yaw motions), and several test conditions. Six catheters were placed in each cadaver (30 placements). Post-procedure CT scans allowed comparison of planned and actual catheter position for user error calculation.

RESULTS:
Registration was successful for all five cadaveric specimens (average SRE 0.429 mm, ±0.108). Accuracy of TRE was under 1.2mm throughout specimen movements of low and high velocities of roll, pitch, and yaw movements, with the slowest recalibration time of 0.23 seconds. There were no statistically significant differences in SRE when the specimens were draped or fully undraped (p-value = 0.336). Addition of bright light or performance under dim light did not significantly affect SRE (p-value = 0.742 and 0.859, respectively). Average TRE for catheter placements was 0.862 mm (±0.322), and average user error for the was 1.674 mm (±1.195).

CONCLUSION:
This computer vision-based registration system provides real-time tracking of cadaveric heads with recalibration time of less than one-quarter of a second with sub-millimetric accuracy, and enabled catheter placements with millimetric accuracy. Using this approach to guide bedside ventriculostomy could reduce complications, improve safety, and could be extrapolated to other frameless stereotactic applications in awake, non-immobilized patients.
182 Predictors of Six-Month Inability to Return to Work in Previously Employed Subjects After Mild Traumatic Brain Injury: A TRACK-TBI Pilot Study
Authors: Yue John K. , Phelps Ryan R. L. , Hemmerle Debra P. , Upadhyayula Pavan S. , Winkler Ethan A. , Deng Hansen , Chang Diana , Vassar Mary , Taylor Sabrina , Schnyer David , Lingsma Hester F. , Puccio Ava , Yuh Esther , Mukherjee Pratik , Huang Michael C. , Ngwenya Laura B. , Valadka Alex B. , Markowitz Amy , Okonkwo David O. , Manley Geoffrey T. 
Published: March 2022

INTRODUCTION:
Return to work (RTW) is an important milestone of mild traumatic brain injury (mTBI) recovery.

METHODS:
Adult subjects from the prospective multicenter TRACK-TBI Pilot study with mTBI (GCS 13-15) who were employed at baseline, with completed three-and six-month RTW status, and three-month Acute Concussion Evaluation (ACE), were extracted. Univariate and multivariable analyses were performed for six-month RTW, focusing on baseline employment, three-month RTW, and three-month ACE domains (physical, cognitive, sleep, and/or emotional postconcussional symptoms (PCS)). Odds ratios (OR) and 95% confidence intervals [CI] were reported.

RESULTS:
In 152 patients aged 40.7 ± 15.0 years, 72% were employed full-time at baseline. Three- and six-month RTW were 77.6% and 78.9%, respectively. At three months, 59.2%, 47.4%, 46.1% and 31.6% scored positive for ACE physical, cognitive, sleep, and emotional PCS domains, respectively. Three-month RTW predicted six-month RTW (OR = 19.80, 95% CI [7.61-51.52]). On univariate analysis, scoring positive in any three-month ACE domain predicted inability for six-month RTW (OR = 0.10-0.11). On multivariable analysis, emotional symptoms predicted inability to six-month RTW (OR = 0.19 [0.04-0.85]). Subjects who scored positive in all four ACE domains were more likely to be unable to RTW at six-months (4 domains: RTW = 58.3%, vs. 0-to-3 domains: RTW = 9.5%; multivariable OR = 0.09 [0.02-0.33]).

CONCLUSION:
Three-month post-injury is an important time point at which RTW status and PCS should be assessed, as both are prognostic markers for six-month RTW. Clinicians should be particularly vigilant of patients presenting with emotional symptoms and/or with symptoms across multiple PCS categories, as these patients are at further risk of inability to RTW and may benefit from targeted evaluation and support.
183 Predicting Vasospasm and Mortality in Early Severe TBI: A Model Using Serum Cytokines and Clinical Data
Authors: Rindler Rima S. , Robertson Henry , DeYampert LaShondra , Eshraghi Sheila , Schobel-McHugh; Eric Elster Seth , Boulis Nicholas M. , Grossberg Jonathan A. 
Published: March 2022

INTRODUCTION:
It is difficult to predict outcomes in patients with severe traumatic brain injury (sTBI) using current clinical tools.

METHODS:
Adult civilian patients were prospectively enrolled in the sTBI arm of the Surgical Critical Care Initiative (SC2i). Patient clinical and serum inflammatory and neuronal protein data were combined and evaluated using the machine learning methods of LASSO and CART to construct parsimonious models for predicting development of post-traumatic vasospasm and mortality. Cross validations were performed to assess the robustness of conclusions. Missing data were imputed with random forest techniques; only variables with less than 10% missingness were included.

RESULTS:
There were 53 patients, of whom 36 (67.9%) developed vasospasm and 10 (18.9%) died. The mean age was 39.2; 22.6% were female. There were an equal number of white (25) and black (25) patients. For vasospasm, LASSO identified Eotaxin and Marshall classification of traumatic brain injury as predictors (XV AUC = 0.77). CART identified S100B as a predictor (full data AUC = 0.75). For mortality, LASSO identified S100B and sRAGE (XV AUC = 0.97), while CART identified S100B (full data AUC = 0.912).

CONCLUSION:
Inflammatory and glial-specific protein levels following sTBI may have predictive value that exceeds conventional clinical variables for certain outcomes. Eotaxin, S100B and radiographic findings highly predict development of post-traumatic vasospasm. S100B and sRAGE highly predict mortality. These results warrant validation in a prospective cohort.
184 Placental Mesenchymal Stromal Cells Seeded on an Extracellular Matrix Scaffold Improve Motor Function Recovery After Acute Spinal Cord Injury
Authors: Kulubya Edwin , Jackson Jordan , Bhaskara Mounika , Kumar Priya , Pivetti Christopher , Avallone Samantha , Paxton Zachary , Reed Camille , Mor Sirjan , Wang Aijun , Farmer Diana 
Published: March 2022

INTRODUCTION:
Spinal cord injury (SCI) is a devasting disease associated with severe disability and no effective cure. SCI involves a primary traumatic injury followed by a secondary injury characterized by inflammation, ischemia, and formation of a glial scar. Cellular therapies aim to minimize the secondary injury by protecting the remaining cells and promoting neuronal and glial regeneration. We have shown placental mesenchymal stromal cells (PMSCs) applied in utero improve ambulatory function and preserve motor neurons in an ovine model of spina bifida and have begun a first-in-human clinical trial for fetal spina bifida.

METHODS:
Female Sprague Dawley rats were given a right C5 hemi-contusion injury using an RWD Precise Impactor and 8 rats served as sham surgery controls. Immediately following injury, rats were treated with an ECM only (n = 9) or an ECM seeded with 3 x 105 PMSCs (PMSC-ECM, n = 11). Weekly motor function testing included Irvine, Beatties, and Bresnahan (IBB) Forelimb Recovery Scale testing by blinded reviewers. After 8 weeks, rats were euthanized, and tissue collected for histology.

RESULTS:
Four second trimester PMSC cell lines were evaluated with our established anti-apoptotic neuroprotection assay and a single cell line was chosen based on increased neurite outgrowths. Within the PMSC-ECM group, rats had statistically significant improvement in their IBB scores between week 1 and week 8 (p = 0.002) compared to ECM only group, where rats did not show improvement (p = 0.063). When comparing IBB scores between groups at week 8, PMSC-ECM rats had a significantly higher IBB score compared to ECM only rats (p = 0.015).

CONCLUSION:
PMSCs improved motor function recovery in a rodent model of SCI. Further studies include immunohistochemical analysis and delivering PMSC derived exosomes as a cell-free treatment.
186 Dorsal Root Ganglion Stimulation as Rescue Therapy for Intractable Pain Following Failed Spinal Cord Stimulation
Authors: Mandelberg Nataniel , Chapman Kenneth , Spiegel Matthew , van Helmond Noud , Patel Kiran , Yang Ajax , Deer Timothy R. , Mogilner Alon Y. 
Published: March 2022

INTRODUCTION:
Despite the demonstrated benefits of spinal cord stimulation (SCS) in patient suffering from chronic pain, loss of efficacy continues to be the primary reason for explant. In order to restore relief in these failed patients, delivery of alternative electrical current can be considered to ‘salvage’ the therapy. Dorsal root ganglion stimulation (DRG-S) is a neuromodulatory technique which acts on a different anatomic target, thereby yielding distinct mechanisms of action and should be considered for such salvage therapy.

METHODS:
This was multicenter retrospective chart review over years 2016-2020 of habituated SCS patients who were later salvaged with DRG-S. Primary endpoints were health related quality of life metrics. Data was gathered preop salvage DRG-S and compared to patients’ last follow-up.

RESULTS:
Fifty-five failed SCS patients were salvaged with DRG-S. The median age was 57 and the most common diagnoses were complex regional pain syndrome and failed back surgery syndrome. Failed waveforms included tonic (n = 27), high frequency (n = 9) and burst (n = 19). The majority of DRG-S leads were placed at bilateral T12 and S1. The mean follow up duration of salvage DRG-S was 27 months. All indices were significantly improved with salvage DRG-S. Numeric rating scale scores decreased from mean 8.7 to 3.8, with 80% of patients achieving at least one minimum clinically important difference ( = 30% improvement). Mean Oswestry disability index scores improved from 65 to 31, signifying an improvement from mostly crippled to moderate disability. EQ5D-5L improved from 0.402 to 0.732. Oral morphine equivalents declined from mean 62 to 38.

CONCLUSION:
These data strongly support DRG-S efficacy in the stable treatment of pain in patients who have previously failed to receive persistent benefit from dorsal column SCS. DRG-S therapy reduces pain and disability while improving quality of life.
193 Arachnoid Cysts as Genetically-encoded Harbingers of Neurodevelopmental Pathology
Authors: Kundishora Adam , Kiziltug Emre , Allington Garrett , Allocco August A. , Smith Hannah , Ocken Jack , Moreno-De-Luca Andres , DiLuna Michael , Jin Sheng C. , Kahle Kristopher 
Published: March 2022

INTRODUCTION:
Arachnoid cysts (ACs) are the most common congenital intracranial lesions. While familial cases implicate genetic factors, their ultimate cause remains unknown. Herein, we describe a multi-omics approach to disease state characterization including traditional whole exome sequencing, integrative genomics with analytics of large bulk-RNA and single cell RNA sequencing (scRNAseq) data, and a novel phenomics technique using natural language processing and Human Phenotypic Ontological (HPO) language clustering.

METHODS:
Whole exome sequencing was performed on 1560 individuals (520 parent-offspring "trios"). Genes with likely pathogenic mutations were defined as those with >1 de novo variant (DNV) reaching threshold for exome-wide significance (p<2.5 x 10-6) and having high pLI score (>0.9). This high-confidence pathogenic gene set and a secondary probable pathogenic gene set (>1 DNV, regardless of exome-wide significance or pLI score) were analyzed in bulk-RNA and scRNAseq datasets to assess spatiotemporal and cell-type relationships of gene expression. Phenomic analysis was conducted by subjecting patient medical records to a natural-language-processing (NLP) algorithm. Phenotypes were catalogued with the Human Phenotype Ontology (HPO) language tree and mapped with uniform manifold approximation and projection (UMAP) clustering.

RESULTS:
7 genes reached our pathogenic threshold, ADNP, ARIDB1, KDM5C, PURA, FOXP1, MAP2K1, and SCN2A. Strikingly, all but SCN2A play critical roles in epigenetic regulation of gene expression in the developing brain. Bulk-RNA datasets reveal that these genes converge in networks essential for chromatin remodeling and mRNA processing. scRNAseq datasets revealed an association with excitatory and inter-neurons known to play a role in developmental delay. HPO clustering revealed four major phenotypic clusters defined by neurodevelopmental delay (NDD), seizures, both or asymptomatic. In a subgroup of traditionally phenotyped patients, there was statistically significant enrichment of neuraxial phenotypes - including NDD - among those harboring DNVs.

CONCLUSION:
This novel association between ACs and multiple epigenetic regulators of gene expression provides the first insight into intracranial AC pathobiology. HPO clustering reveals clinically relevant subsets of ACs and implies that traditionally symptomatic or asymptomatic ACs may be harbingers of genetically-driven aberrant neurodevelopment.