Characterizing utilization patterns and reoperation risk factors of interspinous process devices: analysis of a national claims database.

INTRODUCTION: Interspinous process devices (IPDs) were developed as minimally invasive alternatives to open decompression surgery for spinal stenosis. However, given high treatment failure and reoperation rates, there has been minimal adoption by spine surgeons. This study leveraged a national claims database to characterize national IPD usage patterns and postoperative outcomes after IPD implantation. METHOD: Using the PearlDiver database, we identified all patients who underwent 1- or 2-level IPD implantation between 2010 and 2018. Univariate and multivariable logistic regression was performed to identify predictors of the number of IPD levels implanted and reoperation up to 3 years after the index surgery. Right-censored Kaplan-Meier curves were plotted for duration of reoperation-free survival and compared with log-rank tests. RESULTS: Patients (n = 4865) received 1-level (n = 3246) or 2-level (n = 1619) IPDs. Patients who were older (adjusted odds ratio [aOR] 1.02, 95% confidence interval [CI] 1.01-1.03, P < .001), male (aOR 1.31, 95% CI 116-1.50, P < .001), and obese (aOR 1.19, 95% CI 1.05-1.36, P < .01) were significantly more likely to receive a 2-level IPD than to receive a 1-level IPD. The 3-year reoperation rate was 9.3% of patients when mortality was accounted for during the follow-up period. Older age decreased (aOR 0.97, 95% CI 0.97-0.99, P = .0039) likelihood of reoperation, whereas 1-level IPD (aOR 1.37, 95% CI 1.01-1.89, P = .048), Charlson Comorbidity Index (aOR 1.07, 95% CI 1.01-1.14, P = .018), and performing concomitant open decompression increased the likelihood of reoperation (aOR 1.68, 95% CI 1.35-2.09, P = .0014). CONCLUSION: Compared with 1-level IPDs, 2-level IPDs were implanted more frequently in older, male, and obese patients. The 3-year reoperation rate was 9.3%. Concomitant open decompression with IPD placement was identified as a significant risk factor for subsequent reoperation and warrants future investigation.

Predictors of In-Hospital Mortality and Home Discharge in Patients with Aneurysmal Subarachnoid Hemorrhage: A 4-Year Retrospective Analysis.

BACKGROUND: Factors associated with discharge disposition and mortality following aneurysmal subarachnoid hemorrhage (aSAH) are not well-characterized. We used a national all-payer database to identify factors associated with home discharge and in-hospital mortality. METHODS: The National Inpatient Sample was queried for patients with aSAH within a 4-year range. Weighted multivariable logistic regression models were constructed and adjusted for age, sex, race, household income, insurance status, comorbidity burden, National Inpatient Sample SAH Severity Score, disease severity, treatment modality, in-hospital complications, and hospital characteristics (size, teaching status, and region). RESULTS: Our sample included 37,965 patients: 33,605 were discharged alive and 14,350 were discharged home. Black patients had lower odds of in-hospital mortality compared with White patients (adjusted odds ratio [aOR] = 0.67, 95% confidence interval [CI] 0.52-0.86, p = 0.002). Compared with patients with private insurance, those with Medicare were less likely to have a home discharge (aOR = 0.58, 95% CI 0.46-0.74, p < 0.001), whereas those with self-pay (aOR = 2.97, 95% CI 2.29-3.86, p < 0.001) and no charge (aOR = 3.21, 95% CI 1.57-6.55, p = 0.001) were more likely to have a home discharge. Household income percentile was not associated with discharge disposition or in-hospital mortality. Paradoxically, increased number of Elixhauser comorbidities was associated with significantly lower odds of in-hospital mortality. CONCLUSIONS: We demonstrate independent associations with hospital characteristics, patient characteristics, and treatment characteristics as related to discharge disposition and in-hospital mortality following aSAH, adjusted for disease severity.

Unexpected Roles for the Second Brain: Enteric Nervous System as Master Regulator of Bowel Function.

At the most fundamental level, the bowel facilitates absorption of small molecules, regulates fluid and electrolyte flux, and eliminates waste. To successfully coordinate this complex array of functions, the bowel relies on the enteric nervous system (ENS), an intricate network of more than 500 million neurons and supporting glia that are organized into distinct layers or plexi within the bowel wall. Neuron and glial diversity, as well as neurotransmitter and receptor expression in the ENS, resembles that of the central nervous system. The most carefully studied ENS functions include control of bowel motility, epithelial secretion, and blood flow, but the ENS also interacts with enteroendocrine cells, influences epithelial proliferation and repair, modulates the intestinal immune system, and mediates extrinsic nerve input. Here, we review the many different cell types that communicate with the ENS, integrating data about ENS function into a broader view of human health and disease. In particular, we focus on exciting new literature highlighting relationships between the ENS and its lesser-known interacting partners.

Sympathetic Input to Multiple Cell Types in Mouse and Human Colon Produces Region-Specific Responses.

BACKGROUND & AIMS: The colon is innervated by intrinsic and extrinsic neurons that coordinate functions necessary for digestive health. Sympathetic input suppresses colon motility by acting on intrinsic myenteric neurons, but the extent of sympathetic-induced changes on large-scale network activity in myenteric circuits has not been determined. Compounding the complexity of sympathetic function, there is evidence that sympathetic transmitters can regulate activity in non-neuronal cells (such as enteric glia and innate immune cells). METHODS: We performed anatomical tracing, immunohistochemistry, optogenetic (GCaMP calcium imaging, channelrhodopsin), and colon motility studies in mice and single-cell RNA sequencing in human colon to investigate how sympathetic postganglionic neurons modulate colon function. RESULTS: Individual neurons in each sympathetic prevertebral ganglion innervated the proximal or distal colon, with processes closely opposed to multiple cell types. Calcium imaging in semi-intact mouse colon preparations revealed changes in spontaneous and evoked neural activity, as well as activation of non-neuronal cells, induced by sympathetic nerve stimulation. The overall pattern of response to sympathetic stimulation was unique to the proximal or distal colon. Region-specific changes in cellular activity correlated with motility patterns produced by electrical and optogenetic stimulation of sympathetic pathways. Pharmacology experiments (mouse) and RNA sequencing (human) indicated that appropriate receptors were expressed on different cell types to account for the responses to sympathetic stimulation. Regional differences in expression of α-1 adrenoceptors in human colon emphasize the translational relevance of our mouse findings. CONCLUSIONS: Sympathetic neurons differentially regulate activity of neurons and non-neuronal cells in proximal and distal colon to promote distinct changes in motility patterns, likely reflecting the distinct roles played by these 2 regions.

Inpatient virtual shared medical appointments to improve health literacy, increase patient self-efficacy, and reduce provider burnout in acute cerebrovascular pathology patients and their caregivers: a pilot study.

OBJECTIVE: Admission to the hospital for an acute cerebrovascular condition such as stroke or brain hemorrhage can be a traumatic and disorienting experience for patients and their family members. The COVID-19 pandemic has further intensified this experience in addition to exacerbating clinician and resident burnout. To ameliorate some of these concerns, a team of resident and medical student trainees implemented a virtual shared medical appointment (vSMA) program for inpatients with acute cerebrovascular disorders and their caregivers. The authors hypothesized that an early intervention in the form of a vSMA improves patient and caregiver health literacy and preparedness while simultaneously educating clinical trainees on effective communication skills and reducing clinician burnout. METHODS: Patients and caregivers of admitted patients were identified through a census of neurosurgery, neurocritical care, and neurology electronic medical records. A weekly 60-minute secure virtual session consisted of introductions and a 10-minute standardized presentation on cerebrovascular disease management, followed by participant-guided discussion. Participants completed presession and postsession surveys. Through this small feasibility study data were obtained regarding present challenges, both expected and unforeseen. RESULTS: A total of 170 patients were screened, and 13 patients and 26 caregivers participated in at least 1 vSMA session. A total of 6 different healthcare providers facilitated sessions. The vSMA program received overwhelmingly positive feedback from caregivers. Survey responses demonstrated that 96.4% of caregivers and 75% of patients were satisfied with the session, 96.4% of caregivers and 87.5% of patients would recommend this type of appointment to a friend or family member, and 88.8% of providers reported feeling validated by conducting the session. The participant group had a 20% greater percentage of patients discharged home without home needs compared to the nonparticipant group. The primary obstacles encountered included technological frustrations with the consent process and the sessions themselves. CONCLUSIONS: Implementation of a vSMA program at a tertiary care center during a pandemic was feasible. Themes caregivers expressed on the postsession survey included better understanding of caring for a stroke patient and coping with the unpredictability of a patient's prognosis. The pandemic has precipitated shifts toward telehealth, but this study highlights the importance of avoiding marginalization of elderly and less technologically inclined populations.

Robust, 3-Dimensional Visualization of Human Colon Enteric Nervous System Without Tissue Sectioning.

BACKGROUND & AIMS: Small, 2-dimensional sections routinely used for human pathology analysis provide limited information about bowel innervation. We developed a technique to image human enteric nervous system (ENS) and other intramural cells in 3 dimensions. METHODS: Using mouse and human colon tissues, we developed a method that combines tissue clearing, immunohistochemistry, confocal microscopy, and quantitative analysis of full-thickness bowel without sectioning to quantify ENS and other intramural cells in 3 dimensions. RESULTS: We provided 280 adult human colon confocal Z-stacks from persons without known bowel motility disorders. Most of our images were of myenteric ganglia, captured using a 20× objective lens. Full-thickness colon images, viewed with a 10× objective lens, were as large as 4 × 5 mm2. Colon from 2 pediatric patients with Hirschsprung disease was used to show distal colon without enteric ganglia, as well as a transition zone and proximal pull-through resection margin where ENS was present. After testing a panel of antibodies with our method, we identified 16 antibodies that bind to molecules in neurons, glia, interstitial cells of Cajal, and muscularis macrophages. Quantitative analyses demonstrated myenteric plexus in 24.5% ± 2.4% of flattened colon Z-stack area. Myenteric ganglia occupied 34% ± 4% of myenteric plexus. Single myenteric ganglion volume averaged 3,527,678 ± 573,832 mm3 with 38,706 ± 5763 neuron/mm3 and 129,321 ± 25,356 glia/mm3. Images of large areas provided insight into why published values of ENS density vary up to 150-fold-ENS density varies greatly, across millimeters, so analyses of small numbers of thin sections from the same bowel region can produce varying results. Neuron subtype analysis revealed that approximately 56% of myenteric neurons stained with neuronal nitric oxide synthase antibody and approximately 33% of neurons produce and store acetylcholine. Transition zone regions from colon tissues of patients with Hirschsprung disease had ganglia in multiple layers and thick nerve fiber bundles without neurons. Submucosal neuron distribution varied among imaged colon regions. CONCLUSIONS: We developed a 3-dimensional imaging method for colon that provides more information about ENS structure than tissue sectioning. This approach could improve diagnosis for human bowel motility disorders and may be useful for other bowel diseases as well.

Prone Position Ventilation in Neurologically Ill Patients: A Systematic Review and Proposed Protocol.

OBJECTIVES: Prone positioning has been shown to be a beneficial adjunctive supportive measure for patients who develop acute respiratory distress syndrome. Studies have excluded patients with reduced intracranial compliance, whereby patients with concomitant neurologic diagnoses and acute respiratory distress syndrome have no defined treatment algorithm or recommendations for management. In this study, we aim to determine the safety and feasibility of prone positioning in the neurologically ill patients. DESIGN AND SETTING: A systematic review of the literature, performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses 2009 guidelines, yielded 10 articles for analysis. Using consensus from these articles, in combination with review of multi-institutional proning protocols for patients with nonneurologic conditions, a proning protocol for patients with intracranial pathology and concomitant acute respiratory distress syndrome was developed. MEASUREMENTS AND MAIN RESULTS: Among 10 studies included in the final analysis, we found that prone positioning is safe and feasible in the neurologically ill patients with acute respiratory distress syndrome. Increased intracranial pressure and compromised cerebral perfusion pressure may occur with prone positioning. We propose a prone positioning protocol for the neurologically ill patients who require frequent neurologic examinations and intracranial monitoring. CONCLUSIONS: Although elevations in intracranial pressure and reductions in cerebral perfusion pressure do occur during proning, they may not occur to a degree that would warrant exclusion of prone ventilation as a treatment modality for patients with acute respiratory distress syndrome and concomitant neurologic diagnoses. In cases where intracranial pressure, cerebral perfusion pressure, and brain tissue oxygenation can be monitored, prone position ventilation should be considered a safe and viable therapy.

Loss of Tbx3 in murine neural crest reduces enteric glia and causes cleft palate, but does not influence heart development or bowel transit.

Transcription factors that coordinate migration, differentiation or proliferation of enteric nervous system (ENS) precursors are not well defined. To identify novel transcriptional regulators of ENS development, we performed microarray analysis at embryonic day (E) 17.5 and identified many genes that were enriched in the ENS compared to other bowel cells. We decided to investigate the T-box transcription factor Tbx3, which is prominently expressed in developing and mature ENS. Haploinsufficiency for TBX3 causes ulnar-mammary syndrome (UMS) in humans, a multi-organ system disorder. TBX3 also regulates several genes known to be important for ENS development. To test the hypothesis that Tbx3 is important for ENS development or function, we inactivated Tbx3 in all neural crest derivatives, including ENS progenitors using Wnt1-Cre and a floxed Tbx3 allele. Tbx3 fl/fl; Wnt1-Cre conditional mutant mice die shortly after birth with cleft palate and difficulty feeding. The ENS of mutants was well-organized with a normal density of enteric neurons and nerve fiber bundles, but small bowel glial cell density was reduced. Despite this, bowel motility appeared normal. Furthermore, although Tbx3 is expressed in cardiac neural crest, Tbx3 fl/fl; Wnt1-Cre mice had structurally normal hearts. Thus, loss of Tbx3 within neural crest has selective effects on Tbx3-expressing neural crest derivatives.

Racial/ethnic differences in survival for patients with gliosarcoma: an analysis of the National cancer database.

PURPOSE: Gliosarcoma is characterized by the World Health Organization as a Grade IV malignant neoplasm and a variant of glioblastoma. The association of race and ethnicity with survival has been established for numerous CNS malignancies, however, no epidemiological studies have reported these findings for patients with gliosarcoma. The aim of this study was to examine differences by race and ethnicity in overall survival, 30-day mortality, 90-day mortality, and 30-day readmission. METHODS: Data were obtained by query of the National Cancer Database (NCDB) for years 2004-2014. Patients with gliosarcoma were identified by International Classification of Diseases for Oncology, Third Edition (ICD-O-3)-Oncology morphologic code 9442/3 and topographical codes C71.0-C71.9. Differences in survival by race/ethnicity were examined using univariable and multivariable Cox proportional hazards models. Readmission and mortality outcomes were examined with univariable and multivariable logistic regression. RESULTS: A total of 1988 patients diagnosed with gliosarcoma were identified (White Non-Hispanic n = 1,682, Black Non-Hispanic n = 165, Asian n = 40, Hispanic n = 101). There were no differences in overall survival, 30- and 90-day mortality, or 30-day readmission between the races and ethnicities examined. Median survival was 10.4 months for White Non-Hispanics (95% CI 9.8, 11.2), 10.2 months for Black Non-Hispanics (95% CI 8.6, 13.1), 9.0 months for Asian Non-Hispanics (95% CI 5.1, 18.2), and 10.6 months for Hispanics (95% CI 8.3,16.2). 7.3% of all patients examined had an unplanned readmission within 30 days. CONCLUSION: Race/ethnicity are not associated with differences in overall survival, 30-day mortality, 90-day mortality, or 30-day readmission following surgical intervention for gliosarcoma.

Successful delayed non-operative management of C2 neurosynchondrosis fractures in a pediatric patient: a case report and review of management strategies and considerations for treatment.

Upper cervical synchondrosis fractures are the most common types of cervical fractures in the pediatric population less than 7 years of age (Blauth et al (Eur Spine J 5:63-70, 1996); Connolly et al (Pediatr Radiol 25(Suppl1):S129-133, 1995); Mandabach et al (Pediatr Neurosurg 19(5):225-232, 1993); Schippers et al (Acta Neurochir 138:524-530, 1990)) The vast majority occur through the dentocentral or basilar synchondrosis. We present the second reported case in recent literature of a unilateral neurosynchondrosis fracture. The patient, a 4-year-old male, was initially managed conservatively with a rigid cervical collar for a period of 3 months. Despite multiple counseling sessions with family, the patient remained poorly compliant with cervical immobilization. After 3 months, imaging demonstrated partial fusion with persistent anterolisthesis of C2 on C3. The decision was made to place the child in external halo fixation as an attempt to achieve fusion prior to committing to internal surgical fixation and the associated sequelae. Immobilization with a hard cervical collar is often first line treatment. In the case of failed fusion, debate exists regarding surgical fixation in children. Occipito-atlanto-axial fusion leads to permanent loss of a significant degree of flexion, extension, and rotatory movement. The pediatric population has a strong propensity to fuse; however, compliance is often a barrier to conservative treatment due to age-related behavioral practices. We demonstrate that even with initial failed fusion and progression of deformity while in a cervical collar, conservative management with external halo fixation can potentially obviate the need for internal fixation.

Laser interstitial thermal therapy followed by minimal-access transsulcal resection for the treatment of large and difficult to access brain tumors.

OBJECTIVE Laser interstitial thermal therapy (LITT), sometimes referred to as "stereotactic laser ablation," has demonstrated utility in a subset of high-risk surgical patients with difficult to access (DTA) intracranial neoplasms. However, the treatment of tumors larger than 10 cm3 is associated with suboptimal outcomes and morbidity. This may limit the utility of LITT in dealing with precisely those large or deep tumors that are most difficult to treat with conventional approaches. Recently, several groups have reported on minimally invasive transsulcal approaches utilizing tubular retracting systems. However, these approaches have been primarily used for intraventricular or paraventricular lesions, and subtotal resections have been reported for intraparenchymal lesions. Here, the authors describe a combined approach of LITT followed by minimally invasive transsulcal resection for large and DTA tumors. METHODS The authors retrospectively reviewed the results of LITT immediately followed by minimally invasive, transsulcal, transportal resection in 10 consecutive patients with unilateral, DTA malignant tumors > 10 cm3. The patients, 5 males and 5 females, had a median age of 65 years. Eight patients had glioblastoma multiforme (GBM), 1 had a previously treated GBM with radiation necrosis, and 1 had a melanoma brain metastasis. The median tumor volume treated was 38.0 cm3. RESULTS The median tumor volume treated to the yellow thermal dose threshold (TDT) line was 83% (range 76%-92%), the median tumor volume treated to the blue TDT line was 73% (range 60%-87%), and the median extent of resection was 93% (range 84%-100%). Two patients suffered mild postoperative neurological deficits, one transiently. Four patients have died since this analysis and 6 remain alive. Median progression-free survival was 280 days, and median overall survival was 482 days. CONCLUSIONS Laser interstitial thermal therapy followed by minimally invasive transsulcal resection, reported here for the first time, is a novel option for patients with large, DTA, malignant brain neoplasms. There were no unexpected neurological complications in this series, and operative characteristics improved as surgeon experience increased. Further studies are needed to elucidate any differences in survival or quality of life metrics.

BAP1 is required prenatally for differentiation and maintenance of postnatal murine enteric nervous system.

Epigenetic regulatory mechanisms are underappreciated, yet are critical for enteric nervous system (ENS) development and maintenance. We discovered that fetal loss of the epigenetic regulator Bap1 in the ENS lineage caused severe postnatal bowel dysfunction and early death in Tyrosinase-Cre Bap1fl/fl mice. Bap1-depleted ENS appeared normal in neonates; however, by P15, Bap1-deficient enteric neurons were largely absent from the small and large intestine of Tyrosinase-Cre Bap1fl/fl mice. Bowel motility became markedly abnormal with disproportionate loss of cholinergic neurons. Single-cell RNA sequencing at P5 showed that fetal Bap1 loss in Tyrosinase-Cre Bap1fl/fl mice markedly altered the composition and relative proportions of enteric neuron subtypes. In contrast, postnatal deletion of Bap1 did not cause enteric neuron loss or impaired bowel motility. These findings suggest that BAP1 is critical for postnatal enteric neuron differentiation and for early enteric neuron survival, a finding that may be relevant to the recently described human BAP1-associated neurodevelopmental disorder.

RIM promotes calcium channel accumulation at active zones of the Drosophila neuromuscular junction.

Synaptic communication requires the controlled release of synaptic vesicles from presynaptic axon terminals. Release efficacy is regulated by the many proteins that comprise the presynaptic release apparatus, including Ca(2+) channels and proteins that influence Ca(2+) channel accumulation at release sites. Here we identify Drosophila RIM (Rab3 interacting molecule) and demonstrate that it localizes to active zones at the larval neuromuscular junction. In Drosophila RIM mutants, there is a large decrease in evoked synaptic transmission because of a significant reduction in both the clustering of Ca(2+) channels and the size of the readily releasable pool of synaptic vesicles at active zones. Hence, RIM plays an evolutionarily conserved role in regulating synaptic calcium channel localization and readily releasable pool size. Because RIM has traditionally been studied as an effector of Rab3 function, we investigate whether RIM is involved in the newly identified function of Rab3 in the distribution of presynaptic release machinery components across release sites. Bruchpilot (Brp), an essential component of the active zone cytomatrix T bar, is unaffected by RIM disruption, indicating that Brp localization and distribution across active zones does not require wild-type RIM. In addition, larvae containing mutations in both RIM and rab3 have reduced Ca(2+) channel levels and a Brp distribution that is very similar to that of the rab3 single mutant, indicating that RIM functions to regulate Ca(2+) channel accumulation but is not a Rab3 effector for release machinery distribution across release sites.

Vitamin D deficiency during the perioperative period increases the rate of hardware failure and the need for revision fusion in adult patients undergoing single-level lumbar spine instrumentation surgery.

Background: Vitamin D has been shown to play important roles in both calcium homeostasis and bone healing. Only three studies have directly examined the relationship between vitamin D deficiency and hardware failure, nonunion, and/or revision surgery. Results are contradictory and none were large enough to provide the statistical power necessary to make definitive conclusions. Methods: A retrospective analysis was performed utilizing the PearlDiver national insurance claims database consisting of 91 million individual patient records. Patients aged 30 and over who underwent a non-segmental posterior lumbar fusion procedure (CPT-22840) in 2012-2019 were included. Data collected included, hardware failure, revision surgery occurrence, and vitamin D deficiency. Hardware failure and revision rates were compared between vitamin D deficient and non-deficient groups. We ran a logistic regression analysis using the following variables: age, Charlson Comorbidity Index (CCI), gender, vitamin D deficiency, obesity, tobacco use, diabetes, osteoporosis, rheumatoid arthritis, and Crohn's disease. Results: 108,137 patients matching inclusion criteria were identified, with an overall hardware failure rate of 2.7% and revision rate of 4.1%. Failure rates were significantly higher for patients diagnosed with vitamin D deficiency during the full queried period (3.3% vs. 2.6%, OR = 1.26; p < 0.0001), as were revision rates (4.3% vs 3.5%, OR = 1.25; p < 0.0001). Patients diagnosed with deficiency pre-surgery, higher failure (3.1% vs 2.6%, OR = 1.19; p < 0.01) and rates of revision (4.4% vs 3.5%, OR = 1.27; p < 0.0001) were increased compared to the non-deficient group. In the logistic regression analysis, vitamin D deficiency remains a significant contributor to hardware failure and revision surgery. Conclusions: These results demonstrate that pre- and/or post-operative vitamin D deficiency is independently correlated with risk for hardware failure and revision surgery in single-level lumbar fusion patients.

Cervical, thoracolumbar, and sacral spine trauma classifications: past, present, and future.

OBJECTIVE: Traumatic spine injuries are a relatively common occurrence and are associated with functional impairment, loss of neurologic function, and spinal deformity. A number of spinal trauma classification systems have been developed with varying degrees of acceptance. This review provides a chronological overview of spinal trauma classification systems, with special consideration towards the benefits and pitfalls related to each. Cervical, thoracolumbar, and sacral trauma classification systems are discussed. METHODS: A review of the literature was performed. Published articles that reported on bony spinal trauma classification systems were examined. No year exemptions were identified. The reference lists of all selected articles were screened for additional studies. Article inclusion and exclusion criteria were defined a priori. RESULTS: A total of 20 classification systems were identified from years 1938-2017. Of these 20 classification systems, 6 were cervical, 11 were thoracolumbar and 3 were sacral. The modernization of bony spinal trauma classification has been characterized by the development of weighted scales that include injury morphology, integrity of associated ligamentous structures and neurologic status. CONCLUSION: For widespread acceptance and adoption in the clinical setting, future spinal trauma scoring classification will need to remain simple, highly reproducible, and impart information with regard to clinical decision-making and prognosis that may be effectively communicated across each medical specialty involved in the care of these patients.

Nonsteroidal Anti-inflammatory Drugs in the Acute Post-operative Period Are Associated With an Increased Incidence of Pseudarthrosis, Hardware Failure, and Revision Surgery Following Single-level Spinal Fusion.

STUDY DESIGN: Retrospective study. SUMMARY OF BACKGROUND DATA: Research has shown that the use of NSAIDs and COX-2 inhibitors increases the risk of pseudoarthrosis following spinal fusion surgery. Pseudoarthrosis can lead to complications such as chronic pain and the need for additional surgeries. OBJECTIVE: The purpose of this study was to examine the relationship between NSAID and COX-2 inhibitor use and pseudarthrosis, hardware complications, and revision surgeries in patients undergoing posterior spinal instrumentation and fusion. METHODS: We queried the PearlDiver database using CPT and ICD-10 codes to identify patients between the ages of 50 and 85 who underwent posterior spinal instrumentation between 2016 and 2019 and experienced pseudarthrosis, hardware failure, or revision surgery. Information regarding age, Charlson Comorbidity Index, tobacco use, osteoporosis, and obesity were extracted from the database along with COX-2 or NSAID use during the first 6-week post-surgery period. Logistic regression was used to identify associations while adjusting for confounders. RESULTS: There were 178,758 patients included in the cohort; 9,586 experienced pseudarthrosis (5.36%), 2828 (1.58%) experienced hardware failure, and 10,457 (5.85%) patients underwent revision fusion surgery. Of these patients 23,602 (13.2%) filled NSAID and 5278 (2.95%) filled COX-2 prescriptions. A significantly higher proportion of patients using NSAIDs experienced pseudarthrosis, hardware failure, and revision surgery compared to patients not taking NSAIDs. COX-2 inhibitors were also associated with a significantly higher rate of pseudarthrosis, hardware failure, and revision surgery. Postoperative ketorolac use was not associated with these complications. Regression models demonstrated that both NSAIDs and COX-2 inhibitors were associated with statistically higher pseudarthrosis, hardware failure, and revision surgery rates. CONCLUSIONS: Both NSAID and COX-2 inhibitor use in the early post-surgical period may be associated with increased rates of pseudarthrosis, hardware failure, and revision surgery in patients undergoing posterior spinal instrumentation and fusion.

Characterizing the Next Generation of Neurosurgeons: A Descriptive Analysis and Publicly Available Web Application of Neurosurgery Residency Programs' Website Data.

OBJECTIVE: Neurosurgery program websites serve as a valuable resource for applicants. However, each website exists in isolation, and it can be difficult to understand the general trends in U.S. neurosurgery resident demographics. In the present study, we collected data from program websites and analyzed the trends in the demographics of the current U.S. neurosurgery residents. METHODS: We used a program list obtained from the American Association of Medical Colleges Electronic Residency Application System to extract data from the current resident complement listed in each program's website, including program, year in program, medical school, sex (male vs. female), graduate and/or PhD degrees, and assessed the trends during 7 years of resident data using linear regression. RESULTS: We identified 116 neurosurgery residency programs in the United States, with 111 providing information on their current resident complement, yielding a dataset of 1599 residents. Of these 1599 residents, 348 (22%) were female, 301 (19%) had a graduate degree in addition to an MD or DO degree, 151 (9.4%) had a PhD degree, 300 (19%) had matched at the program affiliated with their medical school, and 121 (7.6%) had graduated from a foreign medical school. The proportion of matriculating female residents had increased an average of 2.1% annually (95% confidence interval, 0.6%-3.7%) from 2015 to 2021. The other demographic data had not changed significantly during the same period. CONCLUSIONS: In addition to summarizing the current resident demographics, our analysis identified a significant increase in the proportion of female residents between 2015 (15.1%) and 2021 (25.6%). This publicly available dataset should enable additional analyses of the evolution of neurosurgery resident demographics.

Single Nucleus Sequencing of Human Colon Myenteric Plexus-Associated Visceral Smooth Muscle Cells, Platelet Derived Growth Factor Receptor Alpha Cells, and Interstitial Cells of Cajal.

BACKGROUND AND AIMS: Smooth muscle cells (SMCs), interstitial cells of Cajal (ICCs), and platelet-derived growth factor receptor alpha (PDGFRα+) cells (PαCs) form a functional syncytium in the bowel known as the "SIP syncytium." The SIP syncytium works in concert with the enteric nervous system (ENS) to coordinate bowel motility. However, our understanding of individual cell types that form this syncytium and how they interact with each other remains limited, with no prior single-cell RNAseq analyses focused on human SIP syncytium cells. METHODS: We analyzed single-nucleus RNA sequencing data from 10,749 human colon SIP syncytium cells (5572 SMC, 372 ICC, and 4805 PαC nuclei) derived from 15 individuals. RESULTS: Consistent with critical contractile and pacemaker functions and with known enteric nervous system interactions, SIP syncytium cell types express many ion channels, including mechanosensitive channels in ICCs and PαCs. PαCs also prominently express extracellular matrix-associated genes and the inhibitory neurotransmitter receptor for vasoactive intestinal peptide (VIPR2), a novel finding. We identified 2 PαC clusters that differ in the expression of many ion channels and transcriptional regulators. Interestingly, SIP syncytium cells co-express 6 transcription factors (FOS, MEIS1, MEIS2, PBX1, SCMH1, and ZBTB16) that may be part of a combinatorial signature that specifies these cells. Bowel region-specific differences in SIP syncytium gene expression may correlate with regional differences in function, with right (ascending) colon SMCs and PαCs expressing more transcriptional regulators and ion channels than SMCs and PαCs in left (sigmoid) colon. CONCLUSION: These studies provide new insights into SIP syncytium biology that may be valuable for understanding bowel motility disorders and lead to future investigation of highlighted genes and pathways.

Projected timeline to achieve gender balance within the United States neurosurgical workforce exceeds 150 years: a National Plan and Provider Enumeration System analysis.

OBJECTIVE: Despite incremental progress in the representation and proportion of women in the field of neurosurgery, female neurosurgeons still represent an overwhelming minority of the current US physician workforce. Prior research has predicted the timeline by which the proportion of female neurosurgery residents may reach that of males, but none have used the contemporary data involving the entire US neurosurgical workforce. METHODS: The authors performed a retrospective analysis of the National Plan and Provider Enumeration System (NPPES) registry of all US neurosurgeons to determine changes in the proportions of women in neurosurgery across states, census divisions, and census regions between 2010 and 2020. A univariate linear regression was performed to assess historical growth, and then Holt-Winter forecasting was used to predict in what future year gender parity may be reached in this field. RESULTS: A majority of states, divisions, and regions have increased the proportion of female neurosurgeons from 2010. Given current growth rates, the authors found that female neurosurgeons will not reach the proportion of women in the overall medical workforce until 2177 (95% CI 2169-2186). Furthermore, they found that women in neurosurgery will not match their current proportion of the overall US population until 2267 (95% CI 2256-2279). CONCLUSIONS: Whereas many studies have focused on the overall increase of women in neurosurgery in the last decade, this one is the first to compare this growth in the context of the overall female physician workforce and the female US population. The results suggest a longer timeline for gender parity in neurosurgery than previous studies have suggested and should further catalyze the targeted recruitment of women into the field, an overhaul of current policies in place to support and develop the careers of women in neurosurgery, and increased self-reflection and behavioral change from the entire neurosurgery community.

Metastatic Breast Cancer to the Spine: Incidence of Somatic Gene Alterations and Association of Targeted Therapies With Overall Survival.

BACKGROUND: The increase in use of targeted systemic therapies in cancer treatments has catalyzed the importance of identifying patient- and tumor-specific somatic mutations, especially regarding metastatic disease. Mutations found to be most prevalent in patients with metastatic breast cancer include TP53, PI3K, and CDH1. OBJECTIVE: To determine the incidence of somatic mutations in patients with metastatic breast cancer to the spine (MBCS). To determine if a difference exists in overall survival (OS), progression-free survival, and progression of motor symptoms between patients who do or do not undergo targeted systemic therapy after treatment for MBCS. METHODS: This is a retrospective study of patients with MBCS. Review of gene sequencing reports was conducted to calculate the prevalence of various somatic gene mutations within this population. Those patients who then underwent treatment (surgery/radiation) for their diagnosis of MBCS between 2010 and 2020 were subcategorized. The use of targeted systemic therapy in the post-treatment period was identified, and post-treatment OS, progression-free survival, and progression of motor deficits were calculated for this subpopulation. RESULTS: A total of 131 patients were included in the final analysis with 56% of patients found to have a PI3K mutation. Patients who received targeted systemic therapies were found to have a significantly longer OS compared with those who did not receive targeted systemic therapies. CONCLUSION: The results of this study demonstrate that there is an increased prevalence of PI3K mutations in patients with MBCS and there are a significant survival benefit and delay in progression of motor symptoms associated with using targeted systemic therapies for adjuvant treatment.