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.

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 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.

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.

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.

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.

Management of dynamic cervical kyphosis with dorsal epidural lipomatosis: a Hirayama disease variant? Illustrative case.

BACKGROUND: Hirayama disease, a cervical myelopathy characterized most commonly by a self-limiting atrophic weakness of the upper extremities, is a rare entity, scarcely reported in the literature. Diagnosis is made by spinal magnetic resonance imaging (MRI), which typically shows loss of normal cervical lordosis, anterior displacement of the cord during flexion, and a large epidural cervical fat pad. Treatment options include observation or cervical immobilization by collar or surgical decompression and fusion. OBSERVATIONS: Here, the authors report an unusual case of a Hirayama-like disease in a young White male athlete who presented with rapidly progressive paresthesia in all 4 extremities and no weakness. Imaging showed characteristic findings of Hirayama disease as well as worsened cervical kyphosis and spinal cord compression in cervical neck extension, which has not previously been reported. Two-level anterior cervical discectomy and fusion and posterior spinal fusion improved both cervical kyphosis on extension and symptoms. LESSONS: Given the disease's self-limiting nature, and a lack of current reporting, there remains no consensus on how to manage these patients. Such findings presented here demonstrate the potentially heterogeneous MRI findings that can be observed in Hirayama disease and emphasize the utility of aggressive surgical management in young, active patients whereby a cervical collar may not be tolerated.

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.

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.

Prevalence and Influence of Frailty on Hospital Outcomes After Surgical Resection of Spinal Meningiomas.

OBJECTIVE: Frailty has been shown to affect patient outcomes after medical and surgical interventions. The Hospital Frailty Risk Score (HFRS) is a growing metric used to assess patient frailty using International Classification of Diseases, Tenth Revision codes. The goal of this study was to investigate the impact of frailty, assessed by HFRS, on health care resource utilization and outcomes in patients undergoing surgery for spinal meningiomas. METHODS: A retrospective cohort study was performed using the 2016-2019 National Inpatient Sample database. Adult patients with benign or malignant spinal meningiomas, identified using International Classification of Diseases, Tenth Revision, Clinical Modification codes, were stratified by HFRS: low frailty (HFRS <5) and intermediate-high frailty (HFRS ≥5). Patient demographics, hospital characteristics, comorbidities, procedural variables, adverse events, length of stay (LOS), discharge disposition, and cost of admission were assessed. Multivariate regression analysis was used to identify predictors of increased LOS, discharge disposition, and cost. RESULTS: Of the 3345 patients, 530 (15.8%) had intermediate-high frailty. The intermediate-high cohort was significantly older (P < 0.001). More patients in the intermediate-high cohort had ≥3 comorbidities (P < 0.001). In addition, a greater proportion of patients in the intermediate-high cohort experienced ≥1 perioperative adverse events (P < 0.001). Intermediate-high patients experienced greater mean LOS (P < 0.001) and accrued greater costs (P < 0.001). A greater proportion of intermediate-high patients had nonroutine discharges (P < 0.001). On multivariate analysis, increased HFRS (≥5) was independently associated with extended LOS (adjusted odds ratio [aOR], 3.04; P < 0.001), nonroutine discharge (aOR, 1.98; P = 0.006), and increased costs (aOR, 2.39; P = 0.004). CONCLUSIONS: Frailty may be associated with increased health care resource utilization in patients undergoing surgery for spinal meningiomas.

A current review of spinal meningiomas: epidemiology, clinical presentation and management.

PURPOSE: To provide an up-to-date review of the epidemiology, histopathology, molecular biology, and etiology of spinal meningiomas, as well as discuss the clinical presentation, clinical evaluation, and most recent treatment recommendations for these lesions. METHODS: PubMed and Google Scholar search was performed for studies related to meningiomas of the spine. The terms "meningioma," "spinal meningioma," "spine meningioma," "meningioma of the spine," "benign spinal tumors," and "benign spine tumors," were used to identify relevant studies. All studies, including primary data papers, meta-analyses, systematic reviews, general reviews, case reports, and clinical trials were considered for review. RESULTS: Eighty-four studies were identified in the review. There were 22 studies discussing adverse postoperative outcomes, 21 studies discussing tumor genetics, 19 studies discussing epidemiology and current literature, 9 studies discussing radiation modalities and impact on subsequent tumor development, 5 studies on characteristic imaging findings, 5 studies discussing hormone use/receptor status on tumor development, 2 discussing operative techniques and 1 discussing tumor identification. CONCLUSION: Investigations into spinal meningiomas generally lag behind that of intracranial meningiomas. Recent advancements in the molecular profiling of spinal meningiomas has expanded our understanding of these tumors, increasing our appreciation for their heterogeneity. Continued investigation into the defining characteristics of different spinal meningiomas will aid in treatment planning and prognostication.

Higher Hospital Frailty Risk Score is associated with increased complications and healthcare resource utilization after endovascular treatment of ruptured intracranial aneurysms.

AIM: To use the Hospital Frailty Risk Score (HFRS) to investigate the impact of frailty on complication rates and healthcare resource utilization in patients who underwent endovascular treatment of ruptured intracranial aneurysms (IAs). METHODS: A retrospective cohort study was performed using the 2016-2019 National Inpatient Sample database. All adult patients (≥18 years) undergoing endovascular treatment for IAs after subarachnoid hemorrhage were identified using ICD-10-CM codes. Patients were categorized into frailty cohorts: low (HFRS <5), intermediate (HFRS 5-15) and high (HFRS >15). Patient demographics, adverse events, length of stay (LOS), discharge disposition, and total cost of admission were assessed. Multivariate logistic regression analysis was used to identify independent predictors of prolonged LOS, increased cost, and non-routine discharge. RESULTS: Of the 33 840 patients identified, 7940 (23.5%) were found to be low, 20 075 (59.3%) intermediate and 5825 (17.2%) high frailty by HFRS criteria. The rate of encountering any adverse event was significantly greater in the higher frailty cohorts (low: 59.9%; intermediate: 92.4%; high: 99.2%, p<0.001). There was a stepwise increase in mean LOS (low: 11.7±8.2 days; intermediate: 18.7±14.1 days; high: 26.6±20.1 days, p<0.001), mean total hospital cost (low: $62 888±37 757; intermediate: $99 670±63 446; high: $134 937±80 331, p<0.001), and non-routine discharge (low: 17.3%; intermediate: 44.4%; high: 69.4%, p<0.001) with increasing frailty. On multivariate regression analysis, a similar stepwise impact was found in prolonged LOS (intermediate: OR 2.38, p<0.001; high: OR 4.49, p<0.001)], total hospital cost (intermediate: OR 2.15, p<0.001; high: OR 3.62, p<0.001), and non-routine discharge (intermediate: OR 2.13, p<0.001; high: OR 4.17, p<0.001). CONCLUSIONS: Our study found that greater frailty as defined by the HFRS was associated with increased complications, LOS, total costs, and non-routine discharge.

Impact of Affective Disorders on Inpatient Opioid Consumption and Hospital Outcomes Following Open Posterior Spinal Fusion for Adult Spine Deformity.

OBJECTIVE: Affective disorders (ADs) are common and have a profound impact on surgical recovery, though few have studied the impact of ADs on inpatient narcotic consumption. The aim of this study was to assess the impact of ADs on inpatient narcotic consumption and healthcare resource utilization in patients undergoing spinal fusion for adult spinal deformity. METHODS: A retrospective cohort study was performed using the 2016-2017 Premier Healthcare Database. Adults who underwent adult spinal deformity surgery were identified using International Classification of Disease, Tenth Revision, codes. Patients were grouped based on comorbid diagnosis of an AD. Demographics, comorbidities, intraoperative variables, complications, length of stay, admission costs, and nonroutine discharge rates were assessed. Increased inpatient opioid use was categorized by morphine milligram equivalents consumption greater than the 75th percentile. Multivariate regression analysis was used to identify predictors of increased healthcare recourse utilization. RESULTS: Of the 1831 study patients, 674 (36.8%) had an AD. A smaller proportion of patients in the AD cohort were 65+ years of age (P = 0.001), while a greater proportion of patients in the AD cohort identified as non-Hispanic White (P < 0.001). A greater proportion of patients in the AD cohort had increased morphine milligram equivalents consumption (P < 0.001). The AD cohort also had a longer mean length of stay (P < 0.001). A greater proportion of patients in the AD cohort had nonroutine discharges (P = 0.039) and unplanned 30-day readmission (P = 0.041). On multivariate analysis, AD was significantly associated with increased cost (odds ratio: 1.61, P < 0.001) and nonroutine discharge (odds ratio: 1.36, P = 0.035). CONCLUSIONS: ADs may be associated with increased inpatient opioid consumption and healthcare resource utilization.

Association of inpatient opioid consumption on postoperative outcomes after open posterior spinal fusion for adult spine deformity.

INTRODUCTION: Opioids are the most commonly used analgesic in the postoperative setting. However, few studies have analyzed the impact of high inpatient opioid use on outcomes following surgery, with no current studies assessing its effect on patients undergoing spinal fusion for an adult spinal deformity (ASD). Thus, the aim of this study was to investigate risk factors for high inpatient opioid use, as well as to determine the impact of high opioid use on outcomes such as adverse events (AEs), hospital length of stay (LOS), cost of hospital admission, discharge disposition, and readmission rates in patients undergoing spinal fusion for ASD. METHODS: A retrospective cohort study was performed using the Premier healthcare database from the years 2016 and 2017. All adult patients > 40 years old who underwent thoracic or thoracolumbar fusion for ASD were identified using the ICD-10-CM diagnostic and procedural coding system. Patients were then categorized into three cohorts based on inpatient opioid use: Low MME (morphine milligram equivalents), Medium MME, and High MME. Patient demographics, comorbidities, treating hospital characteristics, intraoperative variables, postoperative AEs, LOS, discharge disposition, and total cost of hospital admission were assessed in the analysis. Multivariate regression analysis was done to determine independent predictors of high inpatient MME, prolonged LOS, and increased hospital cost. RESULTS: Of 1673 patients included, 417 (24.9%) were classified as Low MME, 840 (50.2%) as Medium MME, and 416 (24.9%) as High MME. Age significantly decreased with increasing MME (Low: 71.0% 65 + years vs Medium: 62.0% 65 + years vs High: 47.4% 65 + years, p < 0.001), while the proportions of patients presenting with three or more comorbidities were similar across the cohorts (Low: 20.1% with 3 + comorbidities vs Medium: 18.0% with 3 + comorbidities vs High: 24.3% with 3 + comorbidities, p = 0.070). With respect to postoperative outcomes, the proportion of patients who experienced any AE (Low: 60.2% vs Medium: 68.8% vs High: 70.9%, p = 0.002), extended LOS (Low: 6.7% vs Medium: 20.7% vs High: 45.4%, p < 0.001), or non-routine discharge (Low: 66.6% vs Medium: 73.5% vs High: 80.1%, p = 0.003) each increased along with total MME. In addition, rates of 30-day readmission were greatest among the High MME cohort (Low: 8.4% vs Medium: 7.9% vs High: 12.5%, p = 0.022). On multivariate analysis, medium and high MME were associated with prolonged LOS [Medium: OR 4.41, CI (2.90, 6.97); High: OR 13.99, CI (8.99, 22.51), p < 0.001] and increased hospital cost [Medium: OR 1.69, CI (1.21, 2.39), p = 0.002; High: OR 1.66, CI (1.12, 2.46), p = 0.011]. Preadmission long-term opioid use [OR 1.71, CI (1.07, 2.7), p = 0.022], a prior opioid-related disorder [OR 11.32, CI (5.92, 23.49), p < 0.001], and chronic pulmonary disease [OR 1.39, CI (1.06, 1.82), p = 0.018] were each associated with a high inpatient MME on multivariate analysis. CONCLUSION: Our study demonstrated that increasing inpatient MME consumption was associated with extended LOS and increased hospital cost in patients undergoing spinal fusion for ASD. Further studies identifying risk factors for increased MME consumption may provide better risk stratification for postoperative opioid use and healthcare resource utilization.

Hospital Frailty Risk Score Predicts Adverse Events and Readmission Following a Ventriculoperitoneal Shunt Surgery for Normal Pressure Hydrocephalus.

OBJECTIVE: The aim of this study was to evaluate the impact of a Hospital Frailty Risk Score (HFRS) on unplanned readmission and health care resource utilization in normal pressure hydrocephalus (NPH) patients undergoing a ventriculoperitoneal (VP) shunt surgery. METHODS: A retrospective cohort study was performed using the 2016-2019 Nationwide Readmission Database. All NPH patients (≥60 years) undergoing a VP shunt surgery were identified using ICD-10-CM diagnostic and procedural codes. Patients were dichotomized into 2 cohorts as follows: Low HFRS (<5) and Intermediate-High HFRS (≥5). A multivariate logistic regression analysis was then used to identify independent predictors of adverse event (AE) and 30- and 90-day readmission. RESULTS: Of 13,262 patients, 4386 (33.1%) had an Intermediate-High HFRS score. A greater proportion of the Intermediate-High HFRS cohort experienced at least one AE (1.9 vs. 22.1, P < 0.001). The Intermediate-High HFRS cohort also had a longer length of stay (2.3 ± 2.4 days vs. 7.0 ± 7.7 days, P < 0.001), higher non-routine discharge rate (19.9% vs. 39.9%, P < 0.001), and greater admission cost ($14,634 ± 5703 vs. $21,749 ± 15,234, P < 0.001). The Intermediate-High HFRS cohort had higher rates of 30- (7.6% vs. 11.0%, P < 0.001) and 90-day (6.8% vs. 8.3%, P < 0.001) readmissions. On a multivariate regression analysis, Intermediate-High HFRS compared to Low HFRS was an independent predictor of any AE (odds ratio, 16.6; 95% confidence interval, [12.9-21.5]; P < 0.001) and 30-day readmission (odds ratio, 1.4; 95% confidence interval, [1.2-1.7]; P < 0.001). CONCLUSIONS: Our study suggests that frailty, as defined by HFRS, is associated with increased resource utilization in NPH patients undergoing VP shunt surgery. Furthermore, HFRS was an independent predictor of adverse events and 30-day hospital readmission.

Impact of Racial Disparities on All-Cause Mortality in Patients With Tumors of the Spinal Cord or Spinal Meninges: A Propensity-Score Analysis.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The influence that race has on mortality rates in patients with spinal cord tumors is relatively unknown. The aim of this study was to investigate the influence of race on the outcomes of patients with primary malignant or nonmalignant tumors of the spinal cord or spinal meninges. METHODS: The Surveillance, Epidemiology, and End Results (SEER) Registry was used to identify all patients with a code for primary malignant or nonmalignant tumor of the spinal cord (C72.0) or spinal meninges (C70.1) from 1973 through 2016. Racial groups (African-American/Black vs. White) were balanced using propensity-score (PS) matching using a non-parsimonious 1:1 nearest neighbor matching algorithm. Overall survival (OS) estimates were obtained using the Kaplan-Meier method and compared across non-PS-matched and PS-matched groups using log-rank tests. Associations of survival with clinical variables was assessed using doubly robust Cox proportional-hazards (CPH) regression analysis. RESULTS: There were a total of 7,498 patients identified with 648 (6.8%) being African American. African-American patients with primary intradural spine tumors were more likely to die of all causes than were White patients in both the non-PS-matched [HR: 1.26, 95% CI: (1.04, 1.51), P = 0.01] and PS-matched cohorts [HR: 1.64, 95% CI: (1.28, 2.11), P < 0.0001]. On multivariate CPH regression analysis age at diagnosis [HR: 1.03, 95% CI: (1.02, 1.05), P < 0.0001], race [HR: 1.82, 95% CI: (1.22, 2.74), P = 0.004), and receipt of RT [HR: 2.62, 95% CI: (1.56, 4.37), P = 0.0002) were all significantly associated with all-cause mortality, when controlling for other demographic, tumor, and treatment variables. CONCLUSIONS: Our study provides population-based estimates of the prognosis for patients with primary malignant or nonmalignant tumors of the spinal cord or spinal meninges and suggests that race may impact all-cause mortality.

Hospital Frailty Risk Score and Healthcare Resource Utilization After Surgery for Primary Spinal Intradural/Cord Tumors.

OBJECTIVE: The Hospital Frailty Risk Score (HFRS) is a metric that measures frailty among patients in large national datasets using ICD-10 codes. While other metrics have been utilized to demonstrate the association between frailty and poor outcomes in spine oncology, none have examined the HFRS. The aim of this study was to investigate the impact of frailty using the HFRS on complications, length of stay, cost of admission, and discharge disposition in patients undergoing surgery for primary tumors of the spinal cord and meninges. METHODS: A retrospective cohort study was performed using the Nationwide Inpatient Sample database from 2016 to 2018. Adult patients undergoing surgery for primary tumors of the spinal cord and meninges were identified using ICD-10-CM codes. Patients were categorized into 2 cohorts based on HFRS score: Non-Frail (HFRS<5) and Frail (HFRS≥5). Patient characteristics, treatment, perioperative complications, LOS, discharge disposition, and cost of admission were assessed. RESULTS: Of the 5955 patients identified, 1260 (21.2%) were Frail. On average, the Frail cohort was nearly 8 years older (P < .001) and experienced more postoperative complications (P = .001). The Frail cohort experienced longer LOS (P < .001), a higher rate of non-routine discharge (P = .001), and a greater mean cost of admission (P < .001). Frailty was found to be an independent predictor of extended LOS (P < .001) and non-routine discharge (P < .001). CONCLUSION: Our study is the first to use the HFRS to assess the impact of frailty on patients with primary spinal tumors. We found that frailty was associated with prolonged LOS, non-routine discharge, and increased hospital costs.