Epigenetic age biomarkers and risk assessment in adult spinal deformity: a novel association of biological age with frailty and disability.

OBJECTIVE: Surgery for spinal deformity has the potential to improve pain, disability, function, self-image, and mental health. These surgical procedures carry significant risk and require careful selection, optimization, and risk assessment. Epigenetic clocks are age estimation tools derived by measuring the methylation patterns of specific DNA regions. The study of biological age in the adult deformity population has the potential to shed insight onto the molecular basis of frailty and to improve current risk assessment tools. METHODS: Adult patients who underwent deformity surgery were prospectively enrolled. Preoperative whole blood samples were used to assess epigenetic age and telomere length. DNA methylation patterns were quantified and processed to extract 4 principal component (PC)-based epigenetic age clocks (PC Horvath, PC Hannum, PC PhenoAge, and PC GrimAge) and the instantaneous pace of aging (DunedinPACE). Telomere length was assessed using both quantitative polymerase chain reaction (telomere to single gene [T/S] ratio) and a methylation-based telomere estimator (PC DNAmTL). Patient demographic and surgical data included age, BMI, American Society of Anesthesiologists Physical Status Classification System class, and scores on the Charlson Comorbidity Index, adult spinal deformity frailty index (ASD-FI), Edmonton Frail Scale (EFS), Oswestry Disability Index, and Scoliosis Research Society-22r questionnaire (SRS-22r). Medical or surgical complications within 90 days of surgery were collected. Spearman correlations and beta coefficients (ß) from linear regression, adjusted for BMI and sex, were calculated. RESULTS: Eighty-three patients were enrolled with a mean age of 65 years, and 45 were women (54%). All patients underwent posterior fusion with a mean of 11 levels fused and 33 (40%) 3-column osteotomies were performed. Among the epigenetic clocks adjusted for BMI and sex, DunedinPACE showed a significant association with ASD-FI (ß = 0.041, p = 0.002), EFS (ß = 0.696, p = 0.026), and SRS-22r (ß = 0.174, p = 0.013) scores. PC PhenoAge showed associations with ASD-FI (ß = 0.029, p = 0.028) and SRS-22r (ß = 0.159, p = 0.018) scores. PC GrimAge showed associations with ASD-FI (ß = 0.029, p = 0.037) and SRS-22r (ß = 0.161, p = 0.025) scores. Patients with postoperative complications were noted to have shorter telomere length (T/S 0.790 vs 0.858, p = 0.049), even when the analysis controlled for BMI and sex (OR = 1.71, 95% CI 1.07-2.87, p = 0.031). CONCLUSIONS: Epigenetic clocks showed significant associations with markers of frailty and disability, while patients with postoperative complications had shorter telomere length. These data suggest a potential role for aging biomarkers as components of surgical risk assessment. Integrating biological age into current risk calculators may improve their accuracy and provide valuable information for patients, surgeons, and payers.

Failure in Adult Spinal Deformity Surgery: A Comprehensive Review of Current Rates, Mechanisms, and Prevention Strategies.

STUDY DESIGN: Literature review. OBJECTIVE: The aim of this review is to summarize recent literature on adult spinal deformity (ASD) treatment failure as well as prevention strategies for these failure modes. SUMMARY OF BACKGROUND DATA: There is substantial evidence that ASD surgery can provide significant clinical benefits to patients. The volume of ASD surgery is increasing, and significantly more complex procedures are being performed, especially in the aging population with multiple comorbidities. Although there is potential for significant improvements in pain and disability with ASD surgery, these procedures continue to be associated with major complications and even outright failure. METHODS: A systematic search of the PubMed database was performed for articles relevant to failure after ASD surgery. Institutional review board approval was not needed. RESULTS: Failure and the potential need for revision surgery generally fall into 1 of 4 well-defined phenotypes: clinical failure, radiographic failure, the need for reoperation, and lack of cost-effectiveness. Revision surgery rates remain relatively high, challenging the overall cost-effectiveness of these procedures. CONCLUSION: By consolidating the key evidence regarding failure, further research and innovation may be stimulated with the goal of significantly improving the safety and cost-effectiveness of ASD surgery.

Inferior Clinical Outcomes for Patients with Medicaid Insurance After Surgery for Degenerative Lumbar Spondylolisthesis: A Prospective Registry Analysis of 608 Patients.

BACKGROUND: It remains unclear how type of insurance coverage affects long-term, spine-specific patient-reported outcomes (PROs). This study sought to elucidate the impact of insurance on clinical outcomes after lumbar spondylolisthesis surgery. METHODS: The prospective Quality Outcomes Database registry was queried for patients with grade 1 degenerative lumbar spondylolisthesis who underwent single-segment surgery. Twenty-four-month PROs were compared and included Oswestry Disability Index, Numeric Rating Scale (NRS) back pain, NRS leg pain, EuroQol-5D, and North American Spine Society Satisfaction. RESULTS: A total of 608 patients undergoing surgery for grade 1 degenerative lumbar spondylolisthesis (mean age, 62.5 ± 11.5 years and 59.2% women) were selected. Insurance types included private insurance (n = 319; 52.5%), Medicare (n = 235; 38.7%), Medicaid (n = 36; 5.9%), and Veterans Affairs (VA)/government (n = 17; 2.8%). One patient (0.2%) was uninsured and was removed from the analyses. Regardless of insurance status, compared to baseline, all 4 cohorts improved significantly regarding ODI, NRS-BP, NRS-LP, and EQ-5D scores (P < 0.001). In adjusted multivariable analyses, compared with patients with private insurance, Medicaid was associated with worse 24-month postoperative Oswestry Disability Index (ß = 10.2; 95% confidence interval [CI], 3.9-16.5; P = 0.002) and NRS leg pain (ß =1.3; 95% CI, 0.3-2.4; P = 0.02). Medicaid was associated with worse EuroQol-5D scores compared with private insurance (ß = -0.07; 95% CI -0.01 to -0.14; P = 0.03), but not compared with Medicare and VA/government insurance (P > 0.05). Medicaid was associated with lower odds of reaching ODI minimal clinically important difference (odds ratio, 0.2; 95% CI, 0.03-0.7; P = 0.02) compared with VA/government insurance. NRS back pain and North American Spine Society satisfaction did not differ by insurance coverage (P > 0.05). CONCLUSIONS: Despite adjusting for potential confounding variables, Medicaid coverage was independently associated with worse 24-month PROs after lumbar spondylolisthesis surgery compared with other payer types. Although all improved postoperatively, those with Medicaid coverage had relatively inferior improvements.

Decision tree-based machine learning analysis of intraoperative vasopressor use to optimize neurological improvement in acute spinal cord injury.

OBJECTIVE: Previous work has shown that maintaining mean arterial pressures (MAPs) between 76 and 104 mm Hg intraoperatively is associated with improved neurological function at discharge in patients with acute spinal cord injury (SCI). However, whether temporary fluctuations in MAPs outside of this range can be tolerated without impairment of recovery is unknown. This retrospective study builds on previous work by implementing machine learning to derive clinically actionable thresholds for intraoperative MAP management guided by neurological outcomes. METHODS: Seventy-four surgically treated patients were retrospectively analyzed as part of a longitudinal study assessing outcomes following SCI. Each patient underwent intraoperative hemodynamic monitoring with recordings at 5-minute intervals for a cumulative 28,594 minutes, resulting in 5718 unique data points for each parameter. The type of vasopressor used, dose, drug-related complications, average intraoperative MAP, and time spent in an extreme MAP range (< 76 mm Hg or > 104 mm Hg) were collected. Outcomes were evaluated by measuring the change in American Spinal Injury Association Impairment Scale (AIS) grade over the course of acute hospitalization. Features most predictive of an improvement in AIS grade were determined statistically by generating random forests with 10,000 iterations. Recursive partitioning was used to establish clinically intuitive thresholds for the top features. RESULTS: At discharge, a significant improvement in AIS grade was noted by an average of 0.71 levels (p = 0.002). The hemodynamic parameters most important in predicting improvement were the amount of time intraoperative MAPs were in extreme ranges and the average intraoperative MAP. Patients with average intraoperative MAPs between 80 and 96 mm Hg throughout surgery had improved AIS grades at discharge. All patients with average intraoperative MAP > 96.3 mm Hg had no improvement. A threshold of 93 minutes spent in an extreme MAP range was identified after which the chance of neurological improvement significantly declined. Finally, the use of dopamine as compared to norepinephrine was associated with higher rates of significant cardiovascular complications (50% vs 25%, p < 0.001). CONCLUSIONS: An average intraoperative MAP value between 80 and 96 mm Hg was associated with improved outcome, corroborating previous results and supporting the clinical verifiability of the model. Additionally, an accumulated time of 93 minutes or longer outside of the MAP range of 76-104 mm Hg is associated with worse neurological function at discharge among patients undergoing emergency surgical intervention for acute SCI.

Do social determinants of health impact access to neurosurgical care in the United States? A workforce perspective.

OBJECTIVE: This study attempts to use neurosurgical workforce distribution to uncover the social determinants of health that are associated with disparate access to neurosurgical care. METHODS: Data were compiled from public sources and aggregated at the county level. Socioeconomic data were provided by the Brookings Institute. Racial and ethnicity data were gathered from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research. Physician density was retrieved from the Health Resources and Services Administration Area Health Resources Files. Catchment areas were constructed based on the 628 counties with neurosurgical coverage, with counties lacking neurosurgical coverage being integrated with the nearest covered county based on distances from the National Bureau of Economic Research's County Distance Database. Catchment areas form a mutually exclusive and collectively exhaustive breakdown of the entire US population and licensed neurosurgeons. Socioeconomic factors, race, and ethnicity were chosen as independent variables for analysis. Characteristics for each catchment area were calculated as the population-weighted average across all contained counties. Linear regression analysis modeled two outcomes of interest: neurosurgeon density per capita and average distance to neurosurgical care. Coefficient estimates (CEs) and 95% confidence intervals were calculated and scaled by 1 SD to allow for comparison between variables. RESULTS: Catchment areas with higher poverty (CE = 0.64, 95% CI 0.34-0.93) and higher prime age employment (CE = 0.58, 95% CI 0.40-0.76) were significantly associated with greater neurosurgeon density. Among categories of race and ethnicity, catchment areas with higher proportions of Black residents (CE = 0.21, 95% CI 0.06-0.35) were associated with greater neurosurgeon density. Meanwhile, catchment areas with higher proportions of Hispanic residents displayed lower neurosurgeon density (CE = -0.17, 95% CI -0.30 to -0.03). Residents of catchment areas with higher housing vacancy rates (CE = 2.37, 95% CI 1.31-3.43), higher proportions of Native American residents (CE = 4.97, 95% CI 3.99-5.95), and higher proportions of Hispanic residents (CE = 2.31, 95% CI 1.26-3.37) must travel farther, on average, to receive neurosurgical care, whereas people living in areas with a lower income (CE = -2.28, 95% CI -4.48 to -0.09) or higher proportion of Black residents (CE = -3.81, 95% CI -4.93 to -2.68) travel a shorter distance. CONCLUSIONS: Multiple factors demonstrate a significant correlation with neurosurgical workforce distribution in the US, most notably with Hispanic and Native American populations being associated with greater distances to care. Additionally, higher proportions of Hispanic residents correlated with fewer neurosurgeons per capita. These findings highlight the interwoven associations among socioeconomics, race, ethnicity, and access to neurosurgical care nationwide.

Evaluating the Clinical Utility and Cost of Imaging Strategies in Adults with Newly Diagnosed Primary Intradural Spinal Tumors.

OBJECTIVE: In patients with new primary intradural spinal tumors, the best screening strategy for additional central nervous system (CNS) lesions is unclear. The goal of this study was to document the rate of additional CNS tumors in these patients. METHODS: Adults with primary intradural spinal tumors were retrospectively reviewed. Imaging strategy at diagnosis was classified as focused spine (cervical, thoracic, or lumbar), total spine, or complete neuraxis (brain and total spine). Tumor pathology, genetic syndromes, and presence of additional CNS lesions at diagnosis or follow-up were collected. RESULTS: The study comprised 319 patients with mean age of 51 years and mean follow-up of 41 months. In 151 patients with focused spine imaging, 3 (2.0%) were found to have new lesions with 2 (1.4%) requiring treatment. In 35 patients with total spine imaging, there were no additional lesions. In 133 patients with complete neuraxis imaging, 4 (3.0%) were found to have new lesions with 2 (1.5%) requiring treatment. There was no difference in the identification of new lesions (P = 0.542) or new lesions requiring treatment (P = 0.772) across imaging strategies. Among patients without genetic syndromes, rates of new lesions requiring treatment were 1.4% for focused spine, 0% for total spine, and 2.2% for complete neuraxis (P = 0.683). There were no cases of delayed identification causing risk to life or neurological function. Complete neuraxis imaging carried an increased charge of $4420 per patient. CONCLUSIONS: Among patients without an underlying genetic syndrome, the likelihood of identifying additional CNS lesions requiring treatment is low. In appropriate cases, focused spine imaging may be a more cost-effective strategy.

Concordance of common data elements for assessment of subjective cognitive complaints after mild-traumatic brain injury: a TRACK-TBI Pilot Study.

OBJECTIVE: To determine characteristics and concordance of subjective cognitive complaints (SCCs) 6 months following mild-traumatic brain injury (mTBI) as assessed by two different TBI common data elements (CDEs). RESEARCH DESIGN: The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Pilot Study was a prospective observational study that utilized the NIH TBI CDEs, Version 1.0. We examined variables associated with SCC, performance on objective cognitive tests (Wechsler Adult Intelligence Scale, California Verbal Learning Test, and Trail Making Tests A and B), and agreement on self-report of SCCs as assessed by the acute concussion evaluation (ACE) versus the Rivermead Post Concussion Symptoms Questionnaire (RPQ). RESULTS: In total, 68% of 227 participants endorsed SCCs at 6 months. Factors associated with SCC included less education, psychiatric history, and being assaulted. Compared to participants without SCC, those with SCC defined by RPQ performed significantly worse on all cognitive tests. There was moderate agreement between the two measures of SCCs (kappa = 0.567 to 0.680). CONCLUSION: We show that the symptom questionnaires ACE and RPQ show good, but not excellent, agreement for SCCs in an mTBI study population. Our results support the retention of RPQ as a basic CDE for mTBI research. ABBREVIATIONS: BSI-18: Brief Symptom Inventory; 18CDEs: common data elements; CT: computed tomography; CVLT: California Verbal Learning Test; ED: emergency department; GCS: Glasgow coma scale; LOC: loss of consciousnessm; TBI: mild-traumatic brain injury; PTA: post-traumatic amnesia; SCC: subjective cognitive complaints; TBI: traumatic brain injury; TRACK-TBI: Transforming Research and Clinical Knowledge in Traumatic Brain Injury; TMT: Trail Making Test; WAIS-PSI: Wechsler Adult Intelligence Scale, Fourth Edition, Processing Speed Index.

Bone Morphogenic Protein Use in Spinal Surgery.

Bone morphogenic protein (BMP) provides excellent enhancement of fusion in many spinal surgeries. BMP should be a cautionary tale about the use of industry-sponsored research, perceived conflicts of interest, and holding the field of spinal surgery to the highest academic scrutiny and ethical standards. In the case of BMP, not having a transparent base of literature as it was approved led to delays in allowing this superior technology to help patients.