Endoscopic endonasal resection of olfactory tract hamartoma for pediatric epilepsy.

BACKGROUND: Non-hypothalamic glioneural hamartomas are rare entities known to cause medically refractory epilepsy. Olfactory bulb hamartomas, in particular, are exceptionally rare. METHODS: We describe a case of an olfactory bulb hamartoma that was surgically resected at our institution. We also performed a literature review of all glioneural hamartomas and discuss the clinical presentation, diagnosis, and management of these lesions. RESULTS: Herein, we present the unusual case of a typically developing 17-year-old boy with a near life-long history of drug-resistant epilepsy, found to have a 0.8 × 1.0 cm right olfactory bulb hamartoma. Endoscopic endonasal trans-cribriform resection of the lesion led to seizure freedom in the 6-month follow-up period (Engel class 1 outcome). Comprehensive literature review revealed only one other sporadic case, which was also successfully treated with total surgical resection. CONCLUSIONS: Our case of an olfactory bulb hamartoma adds to the limited literature currently available, illustrating key clinical characteristics of these exceedingly rare lesions and outlining an effective, minimally invasive, and low-morbidity treatment strategy.

High inpatient-opioid consumption predicts extended length of hospital stay in patients undergoing spinal fusion for adolescent idiopathic scoliosis.

OBJECTIVES: Opioids are common medications used following spine surgery. However, few studies have assessed the impact of increased inpatient-opioid consumption on outcomes following posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). The aim of this study was to determine the impact of increased inpatient-opioid consumption on hospital length of stay (LOS) following PSF for AIS. METHODS: A retrospective cohort study was performed using the Premier Healthcare Database (2016-2017). Adolescent patients (11-17 years old) who underwent PSF for AIS, identified using ICD-10-CM coding, were stratified by inpatient MME (morphine milligram equivalent) consumption into Low (< 25th percentile for the cohort), Medium (25-75th percentile), and High (> 75th percentile) cohorts. Demographics, comorbidities, intraoperative procedures, perioperative adverse events (AEs), length of hospital stay (LOS), non-routine discharge rates, cost of admission, and 30-day readmission rates were assessed. A logistic multivariate regression analysis was performed to determine the association between inpatient MME consumption and extended LOS. RESULTS: Of the 1042 study patients, 260 (24.9%) had Low-MME consumption, 523 (50.2%) had Medium-MME consumption, and 259 (24.9%) had High-MME consumption. A greater proportion of patients in the High cohort identified as non-Hispanic white (Low: 46.5% vs Medium: 61.4% vs High: 65.3%, p < 0.001), while the proportion of patients reporting any comorbidity did not vary across the cohorts (p = 0.940). The number of post-operative AEs experienced also did not vary across the cohorts (p = 0.629). A greater proportion of patients in the High cohort had an extended LOS (Low: 6.5% vs Medium: 8.6% vs High: 19.7%, p < 0.001), while a greater proportion of patients in the Low cohort had an increased cost of admission (Low: 33.1% vs Medium: 20.3% vs High: 26.6%, p < 0.001). The High cohort had increased 30-day readmission rates relative to the Low and Medium cohorts (Low: 0.8% vs Medium: 0.2% vs High: 1.5%, p = 0.049). Non-routine discharge rates did not vary among the cohorts (p = 0.441). On multivariate analysis, High-MME consumption was significantly associated with extended LOS, while Medium-MME consumption was not [Medium: aOR: 1.48, CI (0.83, 2.74), p = 0.193; High: aOR: 4.43, CI (2.47, 8.31), p < 0.001]. CONCLUSIONS: Our study showed that high post-operative-MME consumption was significantly associated with extended LOS in patients undergoing PSF for AIS. In light of these findings, changes to existing protocols that decrease the reliance on opioids for post-operative analgesia are merited to improve patient outcomes and reduce health-care expenditures.

Primary intraosseous xanthoma of the frontal bone in a child: illustrative case.

BACKGROUND: Skull lesions are a common finding in children, with dermoid cysts and eosinophilic granulomas observed most frequently. However, primary intraosseous xanthomas of the calvaria, which are lytic, expansile lesions that develop without underlying hyperlipidemic disease, are rare in children, with only one prior case reported. OBSERVATIONS: The authors describe the case of a healthy 6-year-old male who presented with a 2-month history of an enlarging midline skull mass that developed after a recent minor trauma. Imaging showed a full-thickness, lytic frontal bone lesion with an aggressive appearance and heterogeneous contrast enhancement. The patient underwent gross-total resection of the lesion with placement of a mesh cranioplasty. Histopathology revealed a primary intraosseous xanthoma. The patient was discharged on postoperative day 2 and required no further treatment at the 1-month follow-up. LESSONS: This is the first reported case of a primary intraosseous xanthoma in the frontal bone of a pediatric patient. It emphasizes the need to include primary xanthomas in the differential diagnosis for pediatric skull lesions, particularly when the lesion has an aggressive radiographic appearance or the patient has a history of focal trauma. Furthermore, our findings indicate that resection, together with subsequent monitoring for lesion reccurrence, is an adequate first-line treatment.

Isolated unilateral alar ligamentous injury: illustrative cases.

BACKGROUND: Isolated unilateral alar ligament injury (IUALI) is a rare and likely underreported occurrence after upper cervical trauma, with only 16 cases documented in the literature to date. Patients generally present with neck pain, and definitive diagnosis is typically made by magnetic resonance imaging (MRI). Unfortunately, likely due in part to its rarity, there are no formal guidelines for the treatment of an IUALI. Furthermore, there is a limited understanding of the long-term consequences associated with its inadequate treatment. OBSERVATIONS: Here, the authors report on three pediatric patients, each found to have an IUALI after significant trauma. All patients presented with neck tenderness, and two of the three had associated pain-limited range of neck motion. Imaging revealed either a laterally deviated odontoid process on cervical radiographs and/or MRI evidence of ligamentous strain or discontinuity. Each patient was placed in a hard cervical collar for 1 to 2 months with excellent resolution of symptoms. A comprehensive review of the literature showed that all patients with IUALI who had undergone external immobilization with either rigid cervical collar or halo fixation had favorable outcomes at follow-up. LESSONS: For patients with IUALI, a moderate course of nonsurgical management with rigid external immobilization appears to be an adequate first-line treatment.

Reduced racial disparities among newborns with intraventricular hemorrhage.

INTRODUCTION: Intraventricular hemorrhage (IVH) can ensue permanent neurologic dysfunction, morbidity, and mortality. While previous reports have identified disparities based on patient gender or weight, no prior study has assessed how race may influence in neonatal or infantile IVH patients. The aim of this study was to investigate the impact of race on adverse event (AE) rates, length of stay (LOS), and total cost of admission among newborns with IVH. METHODS: Using the 2016-2019 National Inpatient Sample database, newborns diagnosed with IVH were identified using ICD-10-CM codes. Patients were stratified based on race. Patient characteristics and inpatient outcomes were assessed. Multivariate logistic regression analyses were used to identify the impact of race on extended LOS and exorbitant cost. RESULTS: Of 1435 patients, 650 were White (45.3%), 270 African American (AA) (18.8%), 300 Hispanic (20.9%), and 215 Other (15.0%). A higher percentage of AA and Other patients than Hispanic and White patients were < 28 days old (p = 0.008). Each of the cohorts had largely similar presenting comorbidities and symptoms, although AA patients did have significantly higher rates of NEC (p < 0.001). There were no observed differences in rates of AEs, rates of mortality, mean LOS, or mean total cost of admission. Similarly, on multivariate analysis, no race was identified as a significant independent predictor of extended LOS or exorbitant cost. CONCLUSIONS: Our study found that in newborns with IVH, race is not associated with proxies of poor healthcare outcomes like prolonged LOS or excessive cost. Further studies are needed to validate these findings.

Impact of a quality improvement initiative and monthly multidisciplinary meetings on outcomes after posterior spinal fusion for adolescent idiopathic scoliosis.

INTRODUCTION: Several studies have demonstrated the benefits of enhanced recovery after surgery (ERAS) protocols for patients with adolescent idiopathic scoliosis (AIS) undergoing posterior spinal instrumented fusion (PSIF). However, there are relatively few studies investigating the effect of regular multidisciplinary team meetings on level selection, surgical performance parameters, and patient outcomes after PSIF for AIS. The aim of this study was to assess changes in intra- and postoperative outcomes following multidisciplinary team meeting implementation for patients undergoing PSIF for AIS. METHODS: The medical records of 96 adolescents (10 to 18 years old) diagnosed with AIS and undergoing PSIF at a major academic institution from 2017 to 2022 were retrospectively reviewed. A quality improvement (QI) initiative was implemented in February 2020, including institution of monthly multidisciplinary conferences focusing on preoperative indications, level selection, postoperative review of surgical performance parameters for previous cases, and discussion and optimization of postoperative ambulation and pain control protocols. Patients were placed into "Pre-QI" (treated pre-February 2020) and "Post-QI" (treated post-February 2020) cohorts. Patient demographics, comorbidities, deformity characteristics, intraoperative variables, ambulation status, postoperative complications, length of stay (LOS), and unplanned readmission rates were assessed. RESULTS: Of the 96 study patients, 44 (45.8%) were in the Pre-QI cohort, and 52 (54.2%) were in the Post-QI cohort. Mean major curve was not significantly different between the two cohorts (Pre-QI: 58.0 ± 7.3° vs Post-QI: 57.9 ± 14.5°, p = 0.169). The Pre-QI cohort had a greater mean minor curve degree (Pre-QI: 42.7 ± 11.8° vs Post-QI: 36.8 ± 12.4, p = 0.008). The Pre-QI cohort had significantly greater mean spinal levels fused (Pre-QI: 11.7 ± 1.7 vs Post-QI: 10.4 ± 2.6, p = 0.009), significantly greater mean estimated blood loss (Pre-QI: 1063.6 ± 631.5 ml vs. Post-QI: 415.8 ± 189.9 ml, p < 0.001), significantly greater mean operative time normalized to levels fused (Pre-QI: 0.6 ± 0.1 h/level fused vs Post-QI: 0.4 ± 0.1 h/level fused, p < 0.001), and a significantly greater proportion of patients with intraoperative drain placement (Pre-QI: 93.2% vs Post-QI: 5.8%, p < 0.001). The Post-QI cohort had significantly shorter time to postoperative ambulation (Pre-QI: 2.1 ± 0.9 days vs Post-QI: 1.3 ± 0.5 days, p < 0.001). A significantly greater proportion of patients in the Pre-QI cohort developed any postoperative complication (Pre-QI: 72.7% vs Post-QI: 34.6%, p < 0.001), and mean LOS was significantly greater among Pre-QI patients (Pre-QI: 4.5 ± 1.1 days vs Post-QI: 3.2 ± 0.8 days, p < 0.001). Discharge disposition (p = 0.758) and 30-day unplanned readmissions (p = 0.207) were similar between the cohorts. CONCLUSIONS: Our findings suggest that monthly multidisciplinary pediatric spine team meetings may improve patient care. Further studies exploring the incorporation of QI implementation with frequent multidisciplinary team meetings into existing ERAS protocols are merited.

Association of Malnutrition with Surgical and Hospital Outcomes after Spine Surgery for Spinal Metastases: A National Surgical Quality Improvement Program Study of 1613 Patients.

Background: Malnutrition is a common condition that may exacerbate many medical and surgical pathologies. However, few have studied the impact of malnutrition on surgical outcomes for patients undergoing surgery for metastatic disease of the spine. This study aims to evaluate the impact of malnutrition on perioperative complications and healthcare resource utilization following surgical treatment of spinal metastases. Methods: We conducted a retrospective cohort study using the 2011-2019 American College of Surgeons National Surgical Quality Improvement Program database. Adult patients with spinal metastases who underwent laminectomy, corpectomy, or posterior fusion for extradural spinal metastases were identified using the CPT, ICD-9-CM, and ICD-10-CM codes. The study population was divided into two cohorts: Nourished (preoperative serum albumin values ≥ 3.5 g/dL) and Malnourished (preoperative serum albumin values < 3.5 g/dL). We assessed patient demographics, comorbidities, intraoperative variables, postoperative adverse events (AEs), hospital LOS, discharge disposition, readmission, and reoperation. Multivariate logistic regression analyses were performed to identify the factors associated with a prolonged length of stay (LOS), AEs, non-routine discharge (NRD), and unplanned readmission. Results: Of the 1613 patients identified, 26.0% were Malnourished. Compared to Nourished patients, Malnourished patients were significantly more likely to be African American and have a lower BMI, but the age and sex were similar between the cohorts. The baseline comorbidity burden was significantly higher in the Malnourished cohort compared to the Nourished cohort. Compared to Nourished patients, Malnourished patients experienced significantly higher rates of one or more AEs (Nourished: 19.8% vs. Malnourished: 27.6%, p = 0.004) and serious AEs (Nourished: 15.2% vs. Malnourished: 22.6%, p < 0.001). Upon multivariate regression analysis, malnutrition was found to be an independent and associated with an extended LOS [aRR: 3.49, CI (1.97, 5.02), p < 0.001], NRD [saturated aOR: 1.76, CI (1.34, 2.32), p < 0.001], and unplanned readmission [saturated aOR: 1.42, CI (1.04, 1.95), p = 0.028]. Conclusions: Our study suggests that malnutrition increases the risk of postoperative complication, prolonged hospitalizations, non-routine discharges, and unplanned hospital readmissions. Further studies are necessary to identify the protocols that pre- and postoperatively optimize malnourished patients undergoing spinal surgery for metastatic spinal disease.

Impact of Procedure Time on First Pass Effect in Mechanical Thrombectomy for Anterior Circulation Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: First pass effect (FPE) is a metric increasingly used to determine the success of mechanical thrombectomy (MT) procedures. However, few studies have investigated whether the duration of the procedure can modify the clinical benefit of FPE. We sought to determine whether FPE after MT for anterior circulation large vessel occlusion acute ischemic stroke is modified by procedural time (PT). METHODS: A multicenter, international data set was retrospectively analyzed for anterior circulation large vessel occlusion acute ischemic stroke treated by MT who achieved excellent reperfusion (thrombolysis in cerebral infarction 2c/3). The primary outcome was good functional outcome defined by 90-day modified Rankin scale scores of 0-2. The primary study exposure was first pass success (FPS, 1 pass vs ≥2 passes) and the secondary exposure was PT. We fit-adjusted logistic regression models and used marginal effects to assess the interaction between PT (≤30 vs >30 minutes) and FPS, adjusting for potential confounders including time from stroke presentation. RESULTS: A total of 1310 patients had excellent reperfusion. These patients were divided into 2 cohorts based on PT: ≤30 minutes (777 patients, 59.3%) and >30 minutes (533 patients, 40.7%). Good functional outcome was observed in 658 patients (50.2%). The interaction term between FPS and PT was significant ( P = .018). Individuals with FPS in ≤30 minutes had 11.5% higher adjusted predicted probability of good outcome compared with those who required ≥2 passes (58.2% vs 46.7%, P = .001). However, there was no significant difference in the adjusted predicted probability of good outcome in individuals with PT >30 minutes. This relationship appeared identical in models with PT treated as a continuous variable. CONCLUSION: FPE is modified by PT, with the added clinical benefit lost in longer procedures greater than 30 minutes. A comprehensive metric for MT procedures, namely, FPE 30 , may better represent the ideal of fast, complete reperfusion with a single pass of a thrombectomy device.

Influence of affective disorders on outcomes after suboccipital decompression for adult Chiari I malformation.

INTRODUCTION: Affective disorders (AD) have been shown to influence patient outcomes and healthcare resource utilization across several pathologies, though this relationship has not been described in patients with Chiari I malformations (CM-I). The aim of this study was to determine the impact of comorbid AD on postoperative events and healthcare resource utilization in adults following suboccipital decompression for CM-I. METHODS: A retrospective study was performed using the 2016-2019 National Inpatient Sample database. Adults who underwent suboccipital decompression for CM-I were identified using ICD-10-CM codes. Patients were stratified into two cohorts, those with AD and those without (No AD). Patient demographics, comorbidities, operative characteristics, perioperative adverse events (AEs), and healthcare resource utilization were assessed. Multivariate logistic regression analyses were used to identify independent predictors of prolonged length of stay (LOS), exorbitant admission costs, and non-routine discharge (NRD). RESULTS: A total of 3985 patients were identified, of which 2780 (69.8%) were in the No AD cohort and 1205 (30.2%) were in the AD cohort. Patient demographics were similar, except for a greater proportion of Female patients than the No AD cohort (p = 0.004). Prevalence of some comorbidities varied between cohorts, including obesity (p = 0.030), ADHD (p < 0.001), GERD (p < 0.001), smoking (p < 0.001), and chronic pulmonary disease (p < 0.001). The AD cohort had a greater proportion of patients with 1-2 (p < 0.001) or ≥ 3 comorbidities (p < 0.001) compared to the No AD cohort. A greater proportion of patients in the AD cohort presented with headache compared to the No AD cohort (p = 0.003). Incidence of syringomyelia was greater in the No AD cohort (p = 0.002). A greater proportion of patients in the No AD cohort underwent duraplasty only (without cervical laminectomy) compared to the AD cohort (p = 0.021). Healthcare resource utilization was similar between cohorts, with no significant differences in mean LOS (No AD: 3.78 ± 3.51 days vs. 3.68 ± 2.71 days, p = 0.659), NRD (No AD: 3.8% vs. AD: 5.4%, p = 0.260), or mean admission costs (No AD: $20,254 ± 14,023 vs. AD: $29,897 ± 22,586, p = 0.284). On multivariate analysis, AD was not independently associated with extended LOS [OR (95%CI): 1.09 (0.72-1.65), p = 0.669], increased hospital costs [OR (95%CI): 0.98 (0.63-1.52), p = 0.930], or NRD [OR (95%CI): 1.39 (0.65-2.96), p = 0.302]. CONCLUSION: Our study suggests that the presence of an AD may not have as much of an impact on postoperative events and healthcare resource utilization in adult patients undergoing Chiari decompression. Additional studies may be warranted to identify other potential implications that AD may have in other aspects of healthcare in this patient population.

Implications of Frailty on Postoperative Health Care Resource Utilization in Ankylosing Spondylitis Patients Undergoing Spine Surgery for Spinal Fractures.

OBJECTIVE: The rise of spinal surgery for ankylosing spondylitis (AS) necessitates balancing health care costs with quality patient care. Frailty has been independently associated with adverse outcomes and increased costs. This study investigates whether frailty is an independent predictor of poor outcomes after elective surgery for AS. METHODS: Using the National Inpatient Sample (NIS) database, a retrospective study was conducted on adult patients with AS who underwent posterior spinal fusion for fracture between 2016 and 2019. Each patient was assigned a modified frailty index (mFI) score and categorized as prefrail (mFI = 0 or 1), moderately frail (mFI = 2), and highly frail (mFI≥3). Multivariate logistic regression analyses were used to identify independent predictors of extended length of stay, non-routine discharge (NRD), and exorbitant admission costs. RESULTS: Of the 1910 patients, 35.3% were prefrail, 31.2% moderately frail, and 33.5% highly frail. Age was significantly different across groups (P < 0.001), and frailty was associated with increased comorbidities (P < 0.001). Mean length of stay (P = 0.007), NRD rate (P < 0.001), and mean cost of admission (P = 0.002) all significantly increased with increasing frailty. However, frailty was not an independent predictor of extended hospital stay, NRD, or higher costs on multivariate analysis. Instead, predictors included multiple adverse events, number of comorbidities, and race. CONCLUSIONS: While frailty in patients with AS is associated with older age, greater comorbidities, and increased adverse events, it was not an independent predictor of extended hospital stay, NRD, or higher hospital costs. Further research is required to understand the full impact of frailty on surgical outcomes and develop effective interventions.

Racial/Ethnic Disparities Among Patients Undergoing Anterior Cervical Discectomy and Fusion or Posterior Cervical Decompression and Fusion for Cervical Spondylotic Myelopathy: A National Administrative Database Analysis.

INTRODUCTION: The aim of this study was to investigate the impact of racial disparities on surgical outcomes for cervical spondylotic myelopathy (CSM). METHODS: Adult patients undergoing anterior cervical discectomy and fusion (ACDF) or posterior cervical decompression and fusion (PCDF) for CSM were identified from the 2016 to 019 National Inpatient Sample Database using the International Classification of Diseases codes. Patients were categorized based on approach (ACDF or PCDF) and race/ethnicity (White, Black, Hispanic). Patient demographics, comorbidities, operative characteristics, adverse events, and health care resource utilization were assessed. Multivariate logistic regression analyses were used to identify independent predictors of extended length of stay (LOS), nonroutine discharge (NRD), and exorbitant costs. RESULTS: A total of 46,500 patients were identified, of which 36,015 (77.5%) were White, 7465 (16.0%) were Black, and 3020 (6.5%) were Hispanic. Black and Hispanic patients had a greater comorbidity burden compared to White patients (P = 0.001) and a greater incidence of any postoperative complication (P = 0.001). Healthcare resource utilization were greater in the PCDF cohort than the ACDF cohort and greater in Black and Hispanic patients compared to White patients (P < 0.001). Black and Hispanic patient race were significantly associated with extended hospital LOS ([Black] odds ratio [OR]: 2.24, P < 0.001; [Hispanic] OR: 1.64, P < 0.001) and NRD ([Black] OR: 2.33, P < 0.001; [Hispanic] OR: 1.49, P = 0.016). Among patients who underwent PCDF, Black race was independently associated with extended hospital LOS ([Black] OR: 1.77, P < 0.001; [Hispanic] OR: 1.47, P = 0.167) and NRD ([Black] OR: 1.82, P < 0.001; [Hispanic] OR: 1.38, P = 0.052). CONCLUSIONS: Our study suggests that patient race may influence patient outcomes and healthcare resource utilization following ACDF or PCDF for CSM.

A novel SMARCC1 BAFopathy implicates neural progenitor epigenetic dysregulation in human hydrocephalus.

Hydrocephalus, characterized by cerebral ventriculomegaly, is the most common disorder requiring brain surgery in children. Recent studies have implicated SMARCC1, a component of the BRG1-associated factor (BAF) chromatin remodelling complex, as a candidate congenital hydrocephalus gene. However, SMARCC1 variants have not been systematically examined in a large patient cohort or conclusively linked with a human syndrome. Moreover, congenital hydrocephalus-associated SMARCC1 variants have not been functionally validated or mechanistically studied in vivo. Here, we aimed to assess the prevalence of SMARCC1 variants in an expanded patient cohort, describe associated clinical and radiographic phenotypes, and assess the impact of Smarcc1 depletion in a novel Xenopus tropicalis model of congenital hydrocephalus. To do this, we performed a genetic association study using whole-exome sequencing from a cohort consisting of 2697 total ventriculomegalic trios, including patients with neurosurgically-treated congenital hydrocephalus, that total 8091 exomes collected over 7 years (2016-23). A comparison control cohort consisted of 1798 exomes from unaffected siblings of patients with autism spectrum disorder and their unaffected parents were sourced from the Simons Simplex Collection. Enrichment and impact on protein structure were assessed in identified variants. Effects on the human fetal brain transcriptome were examined with RNA-sequencing and Smarcc1 knockdowns were generated in Xenopus and studied using optical coherence tomography imaging, in situ hybridization and immunofluorescence. SMARCC1 surpassed genome-wide significance thresholds, yielding six rare, protein-altering de novo variants localized to highly conserved residues in key functional domains. Patients exhibited hydrocephalus with aqueductal stenosis; corpus callosum abnormalities, developmental delay, and cardiac defects were also common. Xenopus knockdowns recapitulated both aqueductal stenosis and cardiac defects and were rescued by wild-type but not patient-specific variant SMARCC1. Hydrocephalic SMARCC1-variant human fetal brain and Smarcc1-variant Xenopus brain exhibited a similarly altered expression of key genes linked to midgestational neurogenesis, including the transcription factors NEUROD2 and MAB21L2. These results suggest de novo variants in SMARCC1 cause a novel human BAFopathy we term 'SMARCC1-associated developmental dysgenesis syndrome', characterized by variable presence of cerebral ventriculomegaly, aqueductal stenosis, developmental delay and a variety of structural brain or cardiac defects. These data underscore the importance of SMARCC1 and the BAF chromatin remodelling complex for human brain morphogenesis and provide evidence for a 'neural stem cell' paradigm of congenital hydrocephalus pathogenesis. These results highlight utility of trio-based whole-exome sequencing for identifying pathogenic variants in sporadic congenital structural brain disorders and suggest whole-exome sequencing may be a valuable adjunct in clinical management of congenital hydrocephalus patients.

Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations.

To elucidate the pathogenesis of vein of Galen malformations (VOGMs), the most common and most severe of congenital brain arteriovenous malformations, we performed an integrated analysis of 310 VOGM proband-family exomes and 336,326 human cerebrovasculature single-cell transcriptomes. We found the Ras suppressor p120 RasGAP (RASA1) harbored a genome-wide significant burden of loss-of-function de novo variants (2042.5-fold, p = 4.79 x 10-7). Rare, damaging transmitted variants were enriched in Ephrin receptor-B4 (EPHB4) (17.5-fold, p = 1.22 x 10-5), which cooperates with p120 RasGAP to regulate vascular development. Additional probands had damaging variants in ACVRL1, NOTCH1, ITGB1, and PTPN11. ACVRL1 variants were also identified in a multi-generational VOGM pedigree. Integrative genomic analysis defined developing endothelial cells as a likely spatio-temporal locus of VOGM pathophysiology. Mice expressing a VOGM-specific EPHB4 kinase-domain missense variant (Phe867Leu) exhibited disrupted developmental angiogenesis and impaired hierarchical development of arterial-capillary-venous networks, but only in the presence of a "second-hit" allele. These results illuminate human arterio-venous development and VOGM pathobiology and have implications for patients and their families.

Socioeconomic and Racial/Ethnic Disparities in Perception of Health Status and Literacy in Spine Oncological Patients: Insights from the All of Us Research Program.

STUDY DESIGN: A cross-sectional study was performed using the National Institutes of Health All of Us survey database. OBJECTIVE: The aim of this study was to assess socioeconomic and racial disparities in the perception of personal health, health literacy, and healthcare access among spine oncology patients. SUMMARY OF BACKGROUND DATA: Racial, ethnic, and socioeconomic disparities in health literacy and perception of health status have been described for many disease processes. However, few studies have assessed the prevalence of these disparities among spine oncology patients. METHODS: Adult spine oncology patients, identified using ICD-9/10-CM codes, were categorized by race/ethnicity: White/Caucasian (WC), Black/African-American (BAA), and Non-White Hispanic (NWH). Demographics and socioeconomic status were assessed. Questionnaire responses regarding baseline health status, perception of health status, health literacy, and barriers to healthcare were compared. RESULTS: Of the 1,175 patients identified, 207 (17.6%) were BAA, 267 (22.7%) were NWH, and 701 (59.7%) were WC. Socioeconomic status varied among cohorts, with WC patients reporting higher levels of education ( P<0.001 ), annual income greater than $50K ( P<0.001 ), and home ownership ( P<0.001 ). BAA and NWH patients reported greater rates of 7-day "Severe fatigue" ( P<0.001 ) and "10/10 pain" ( P<0.001 ) and lower rates of "Completely" able to perform everyday activities ( P<0.001 ). WC patients had a higher response rate for "Excellent/Very Good" regarding their own general health ( P<0.001 ) and quality ( P<0.001 ). The WC cohort had a significantly higher proportion of patients responding "Never" when assessing difficulty understanding ( P<0.001 ) and needing assistance with health materials ( P<0.001 ). BAA and NWH were significantly less likely to report feeling "Extremely" confident with medical forms ( P<0.001 ). BAA and NWH had significantly higher response rates to feeling "Somewhat Worried" about healthcare costs ( P<0.001 ) and with delaying medical care given "Can't Afford Co-pay" ( P<0.001 ). CONCLUSION: We identified disparities in perception of health status, literacy, and access among spine oncology patients. LEVEL OF EVIDENCE: 4.

Effects of delayed ambulation following posterior spinal fusion for adolescent idiopathic scoliosis: a single institutional study.

OBJECTIVE: Mobilizing out of bed and ambulation are key components of recovery following posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS). However, there remains a paucity of studies identifying risk factors associated with delayed ambulation and its impact on postoperative outcomes. The aim of this study was to investigate patient- and surgical-level risk factors associated with delayed ambulation and the ramifications of delayed ambulation on healthcare utilization for patients undergoing PSF for AIS. METHODS: The medical records of 129 adolescent (10-18 years) patients diagnosed with AIS undergoing posterior spinal fusion at a major academic institution between 2013 and 2020 were reviewed. Patients were categorized based on days from surgery to ambulation: early (≤ 1 day), intermediate (2 days), or late (≥ 3 days). Patient demographics, comorbidities, spinal deformity characteristics, intraoperative variables, postoperative complications, LOS, and unplanned readmissions were assessed. The odds ratios for risk-adjusted delayed ambulation and extended LOS were determined via multivariate stepwise logistic regressions. RESULTS: One Hundred and Twenty Nine patients were included in this study, of which 10.8% (n = 14) were classified as Early ambulators, 41.9% (n = 54) Intermediate ambulators, and 47.3% (n = 61) were Late ambulators. Late ambulators were significantly younger than early and intermediate ambulators (Early: 15.7 ± 1.9 years vs. Intermediate: 14.8 ± 1.7 years vs. Late: 14.1 ± 1.9 years, p = 0.010). The primary and secondary spinal curves were significantly worse among Late ambulators (p < 0.001 and p = 0.002 respectively). Fusion levels (p < 0.01), EBL (p = 0.014), and the rate of RBC transfusions (p < 0.001) increased as time to ambulation increased. Transition time from IV to oral pain medications (Early: 1.6 ± 0.8 days vs. Intermediate: 2.2 ± 0.6 days vs. Late: 2.4 ± 0.6 days, p < 0.001) and total hospital length of stay (Early: 3.9 ± 1.4 days vs. Intermediate: 4.7 ± 0.9 days vs. Late: 5.1 ± 1.2 days, p < 0.001) were longer in Late ambulators. On multivariate analysis, significant predictors of delayed ambulation included primary curve degree ≥ 70° [aOR: 5.67 (1.29‒31.97), p = 0.030] and procedure time [aOR: 1.66 (1.1‒2.59), p = 0.019]. CONCLUSIONS: Our study suggests that there may be patient- and surgical-level factors that are independently associated with late ambulation following PSF for AIS, including extent of major curve and length of operative time. Additionally, delayed ambulation has implications to length of hospital stay and postoperative complications.

Association Between Intravenous to Oral Opioid Transition Time and Length of Hospital Stay After Posterior Spinal Fusion for Adolescent Idiopathic Scoliosis.

BACKGROUND: Transitioning from intravenous (IV) to oral opioids after posterior spinal fusion (PSF) for adolescent idiopathic scoliosis (AIS) is necessary during the postoperative course. However, few studies have assessed the effects of longer transition times on hospital length of stay (LOS). This study investigated the impact of longer IV to oral opioid transition times on LOS after PSF for AIS. METHODS: The medical records of 129 adolescents (10-18 years old) with AIS undergoing multilevel PSF at a major academic institution from 2013 to 2020 were reviewed. Patients were categorized by IV to oral opioid transition time: normal (≤2 days) vs prolonged (≥3 days). Patient demographics, comorbidities, deformity characteristics, intraoperative variables, postoperative complications, and LOS were assessed. Multivariate analyses were used to determine odds ratios for risk-adjusted extended LOS. RESULTS: Of the 129 study patients, 29.5% (n = 38) had prolonged IV to oral transitions. Demographics and comorbidities were similar between the cohorts. The major curve degree (P = 0.762) and median (interquartile range) levels fused (P = 0.447) were similar between cohorts, but procedure time was significantly longer in the prolonged cohort (normal: 6.6 ± 1.2 hours vs prolonged: 7.2 ± 1.3 hours, P = 0.009). Postoperative complication rates were similar between the cohorts. Patients with prolonged transitions had significantly longer LOS (normal: 4.6 ± 1.3 days vs prolonged: 5.1 ± 0.8 days, P < 0.001) but similar discharge disposition (P = 0.722) and 30-day readmission rates (P > 0.99). On univariate analysis, transition time was significantly associated with extended LOS (OR: 2.0, 95% CI [0.9, 4.6], P = 0.014), but this assocation was not significant on multivariate analysis (adjusted OR: 2.1, 95% CI [1.3, 4.8], P = 0.062). CONCLUSIONS: Longer postoperative IV to oral opioid transitions after PSF for AIS may have implications for hospital LOS.

Impact of insurance status on healthcare resource utilization and outcomes in adolescent patients presenting with spinal cord injuries.

OBJECTIVE: Insurance disparities have been suggested to influence the medical and surgical outcomes of adult patients with spinal cord injury (SCI), with a paucity of studies demonstrating their impact on the outcomes of pediatric and adolescent SCI patients. The aim of this study was to assess the impact of insurance status on healthcare utilization and outcomes in adolescent patients presenting with SCI. METHODS: An administrative database study was performed using the 2017 admission year from 753 facilities using the National Trauma Data Bank. Adolescent patients (11-17 years old) with cervical/thoracic SCIs were identified using International Classification of Diseases, Tenth Revision, Clinical Modification coding. Patients were categorized by governmental insurance versus private insurance/self-pay. Patient demographics, comorbidities, imaging, procedures, hospital adverse events (AEs), and length of stay (LOS) data were collected. Multivariate regression analyses were used to determine the effect of insurance status on LOS, any imaging or procedure, or any AE. RESULTS: Of the 488 patients identified, 220 (45.1%) held governmental insurance while 268 (54.9%) were privately insured. Age was similar between the cohorts (p = 0.616), with the governmental insurance cohort (GI cohort) having a significantly lower proportion of non-Hispanic White patients than the private insurance cohort (PI cohort) (GI: 43.2% vs PI: 72.4%, p < 0.001). While transportation accident was the most common mechanism of injury for both cohorts, assault was significantly greater in the GI cohort (GI: 21.8% vs PI: 3.0%, p < 0.001). A significantly greater proportion of patients in the PI cohort received any imaging (GI: 65.9% vs PI: 75.0%, p = 0.028), while there were no significant differences in procedures performed (p = 0.069) or hospital AEs (p = 0.386) between the cohorts. The median (IQR) LOS (p = 0.186) and discharge disposition (p = 0.302) were similar between the cohorts. On multivariate analysis, with respect to governmental insurance, private insurance was not independently associated with obtaining any imaging (OR 1.38, p = 0.139), undergoing any procedure (OR 1.09, p = 0.721), hospital AEs (OR 1.11, p = 0.709), or LOS (adjusted risk ratio -2.56, p = 0.203). CONCLUSIONS: This study suggests that insurance status may not independently influence healthcare resource utilization and outcomes in adolescent patients presenting with SCIs. Further studies are needed to corroborate these findings.

Differences in Outcomes and Health Care Resource Utilization After Surgical Intervention for Metastatic Spinal Column Tumor in Safety-Net Hospitals.

STUDY DESIGN: Observational cohort study. OBJECTIVE: The aim of this study was to investigate the association between safety-net hospital (SNH) status and hospital length of stay (LOS), cost, and discharge disposition in patients undergoing surgery for metastatic spinal column tumors. SUMMARY OF BACKGROUND DATA: SNHs serve a high proportion of Medicaid and uninsured patients. However, few studies have assessed the effects of SNH status on outcomes after surgery for metastatic spinal column tumors. PATIENTS AND METHODS: This study was performed using the 2016-2019 Nationwide Inpatient Sample database. All adult patients undergoing metastatic spinal column tumor surgeries, identified using ICD-10-CM coding, were stratified by SNH status, defined as hospitals in the top quartile of Medicaid/uninsured coverage burden. Hospital characteristics, demographics, comorbidities, intraoperative variables, postoperative complications, and outcomes were assessed. Multivariable analyses identified independent predictors of prolonged LOS (>75th percentile of cohort), nonroutine discharge, and increased cost (>75th percentile of cohort). RESULTS: Of the 11,505 study patients, 24.0% (n = 2760) were treated at an SNH. Patients treated at SNHs were more likely to be Black-identifying, male, and lower income quartile. A significantly greater proportion of patients in the non-SNH (N-SNH) cohort experienced any postoperative complication [SNH: 965 (35.0%) vs . N-SNH: 3535 (40.4%), P = 0.021]. SNH patients had significantly longer LOS (SNH: 12.3 ± 11.3 d vs . N-SNH: 10.1 ± 9.5 d, P < 0.001), yet mean total costs (SNH: $58,804 ± 39,088 vs . N-SNH: $54,569 ± 36,781, P = 0.055) and nonroutine discharge rates [SNH: 1330 (48.2%) vs . N-SNH: 4230 (48.4%), P = 0.715) were similar. On multivariable analysis, SNH status was significantly associated with extended LOS [odds ratio (OR): 1.41, P = 0.009], but not nonroutine discharge disposition (OR: 0.97, P = 0.773) or increased cost (OR: 0.93, P = 0.655). CONCLUSIONS: Our study suggests that SNHs and N-SNHs provide largely similar care for patients undergoing metastatic spinal tumor surgeries. Patients treated at SNHs may have an increased risk of prolonged hospitalizations, but comorbidities and complications likely contribute greater to adverse outcomes than SNH status alone. LEVEL OF EVIDENCE: 3.

Genetic dysregulation of an endothelial Ras signaling network in vein of Galen malformations.

To elucidate the pathogenesis of vein of Galen malformations (VOGMs), the most common and severe congenital brain arteriovenous malformation, we performed an integrated analysis of 310 VOGM proband-family exomes and 336,326 human cerebrovasculature single-cell transcriptomes. We found the Ras suppressor p120 RasGAP ( RASA1 ) harbored a genome-wide significant burden of loss-of-function de novo variants (p=4.79×10 -7 ). Rare, damaging transmitted variants were enriched in Ephrin receptor-B4 ( EPHB4 ) (p=1.22×10 -5 ), which cooperates with p120 RasGAP to limit Ras activation. Other probands had pathogenic variants in ACVRL1 , NOTCH1 , ITGB1 , and PTPN11 . ACVRL1 variants were also identified in a multi-generational VOGM pedigree. Integrative genomics defined developing endothelial cells as a key spatio-temporal locus of VOGM pathophysiology. Mice expressing a VOGM-specific EPHB4 kinase-domain missense variant exhibited constitutive endothelial Ras/ERK/MAPK activation and impaired hierarchical development of angiogenesis-regulated arterial-capillary-venous networks, but only when carrying a "second-hit" allele. These results illuminate human arterio-venous development and VOGM pathobiology and have clinical implications.

A novel SMARCC1 -mutant BAFopathy implicates epigenetic dysregulation of neural progenitors in hydrocephalus.

Importance: Hydrocephalus, characterized by cerebral ventriculomegaly, is the most common disorder requiring brain surgery. A few familial forms of congenital hydrocephalus (CH) have been identified, but the cause of most sporadic cases of CH remains elusive. Recent studies have implicated SMARCC1 , a component of the B RG1- a ssociated factor (BAF) chromatin remodeling complex, as a candidate CH gene. However, SMARCC1 variants have not been systematically examined in a large patient cohort or conclusively linked with a human syndrome. Moreover, CH-associated SMARCC1 variants have not been functionally validated or mechanistically studied in vivo . Objectives: The aims of this study are to (i) assess the extent to which rare, damaging de novo mutations (DNMs) in SMARCC1 are associated with cerebral ventriculomegaly; (ii) describe the clinical and radiographic phenotypes of SMARCC1 -mutated patients; and (iii) assess the pathogenicity and mechanisms of CH-associated SMARCC1 mutations in vivo . Design setting and participants: A genetic association study was conducted using whole-exome sequencing from a cohort consisting of 2,697 ventriculomegalic trios, including patients with neurosurgically-treated CH, totaling 8,091 exomes collected over 5 years (2016-2021). Data were analyzed in 2023. A comparison control cohort consisted of 1,798 exomes from unaffected siblings of patients with autism spectrum disorder and their unaffected parents sourced from the Simons simplex consortium. Main outcomes and measures: Gene variants were identified and filtered using stringent, validated criteria. Enrichment tests assessed gene-level variant burden. In silico biophysical modeling estimated the likelihood and extent of the variant impact on protein structure. The effect of a CH-associated SMARCC1 mutation on the human fetal brain transcriptome was assessed by analyzing RNA-sequencing data. Smarcc1 knockdowns and a patient-specific Smarcc1 variant were tested in Xenopus and studied using optical coherence tomography imaging, in situ hybridization, and immunofluorescence microscopy. Results: SMARCC1 surpassed genome-wide significance thresholds in DNM enrichment tests. Six rare protein-altering DNMs, including four loss-of-function mutations and one recurrent canonical splice site mutation (c.1571+1G>A) were detected in unrelated patients. DNMs localized to the highly conserved DNA-interacting SWIRM, Myb-DNA binding, Glu-rich, and Chromo domains of SMARCC1 . Patients exhibited developmental delay (DD), aqueductal stenosis, and other structural brain and heart defects. G0 and G1 Smarcc1 Xenopus mutants exhibited aqueductal stenosis and cardiac defects and were rescued by human wild-type SMARCC1 but not a patient-specific SMARCC1 mutant. Hydrocephalic SMARCC1 -mutant human fetal brain and Smarcc1 -mutant Xenopus brain exhibited a similarly altered expression of key genes linked to midgestational neurogenesis, including the transcription factors NEUROD2 and MAB21L2 . Conclusions: SMARCC1 is a bona fide CH risk gene. DNMs in SMARCC1 cause a novel human BAFopathy we term " S MARCC1- a ssociated D evelopmental D ysgenesis S yndrome (SaDDS)", characterized by cerebral ventriculomegaly, aqueductal stenosis, DD, and a variety of structural brain or cardiac defects. These data underscore the importance of SMARCC1 and the BAF chromatin remodeling complex for human brain morphogenesis and provide evidence for a "neural stem cell" paradigm of human CH pathogenesis. These results highlight the utility of trio-based WES for identifying risk genes for congenital structural brain disorders and suggest WES may be a valuable adjunct in the clinical management of CH patients. KEY POINTS: Question: What is the role of SMARCC1 , a core component of the B RG1- a ssociated factor (BAF) chromatin remodeling complex, in brain morphogenesis and congenital hydrocephalus (CH)? Findings: SMARCC1 harbored an exome-wide significant burden of rare, protein-damaging de novo mutations (DNMs) (p = 5.83 × 10 -9 ) in the largest ascertained cohort to date of patients with cerebral ventriculomegaly, including treated CH (2,697 parent-proband trios). SMARCC1 contained four loss-of-function DNMs and two identical canonical splice site DNMs in a total of six unrelated patients. Patients exhibited developmental delay, aqueductal stenosis, and other structural brain and cardiac defects. Xenopus Smarcc1 mutants recapitulated core human phenotypes and were rescued by the expression of human wild-type but not patient-mutant SMARCC1 . Hydrocephalic SMARCC1 -mutant human brain and Smarcc1 -mutant Xenopus brain exhibited similar alterationsin the expression of key transcription factors that regulate neural progenitor cell proliferation. Meaning: SMARCC1 is essential for human brain morphogenesis and is a bona fide CH risk gene. SMARCC1 mutations cause a novel human BAFopathy we term " S MARCC1- a ssociated D evelopmental D ysgenesis S yndrome (SaDDS)". These data implicate epigenetic dysregulation of fetal neural progenitors in the pathogenesis of hydrocephalus, with diagnostic and prognostic implications for patients and caregivers.