ATF3 is a neuron-specific biomarker for spinal cord injury and ischaemic stroke.

BACKGROUND: Although many molecules have been investigated as biomarkers for spinal cord injury (SCI) or ischemic stroke, none of them are specifically induced in central nervous system (CNS) neurons following injuries with low baseline expression. However, neuronal injury constitutes a major pathology associated with SCI or stroke and strongly correlates with neurological outcomes. Biomarkers characterized by low baseline expression and specific induction in neurons post-injury are likely to better correlate with injury severity and recovery, demonstrating higher sensitivity and specificity for CNS injuries compared to non-neuronal markers or pan-neuronal markers with constitutive expressions. METHODS: In animal studies, young adult wildtype and global Atf3 knockout mice underwent unilateral cervical 5 (C5) SCI or permanent distal middle cerebral artery occlusion (pMCAO). Gene expression was assessed using RNA-sequencing and qRT-PCR, while protein expression was detected through immunostaining. Serum ATF3 levels in animal models and clinical human samples were measured using commercially available enzyme-linked immune-sorbent assay (ELISA) kits. RESULTS: Activating transcription factor 3 (ATF3), a molecular marker for injured dorsal root ganglion sensory neurons in the peripheral nervous system, was not expressed in spinal cord or cortex of naïve mice but was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Additionally, ATF3 protein levels in mouse blood significantly increased 1 day after SCI or ischemic stroke. Importantly, ATF3 protein levels in human serum were elevated in clinical patients within 24 hours after SCI or ischemic stroke. Moreover, Atf3 knockout mice, compared to the wildtype mice, exhibited worse neurological outcomes and larger damage regions after SCI or ischemic stroke, indicating that ATF3 has a neuroprotective function. CONCLUSIONS: ATF3 is an easily measurable, neuron-specific biomarker for clinical SCI and ischemic stroke, with neuroprotective properties. HIGHLIGHTS: ATF3 was induced specifically in neurons of the spinal cord or cortex within 1 day after SCI or ischemic stroke, respectively. Serum ATF3 protein levels are elevated in clinical patients within 24 hours after SCI or ischemic stroke. ATF3 exhibits neuroprotective properties, as evidenced by the worse neurological outcomes and larger damage regions observed in Atf3 knockout mice compared to wildtype mice following SCI or ischemic stroke.

Correction: Expert-augmented automated machine learning optimizes hemodynamic predictors of spinal cord injury outcome.

[This corrects the article DOI: 10.1371/journal.pone.0265254.].

Safety and comparative efficacy of initiating low-molecular-weight heparin within 24 hours of injury or surgery for venous thromboembolism prophylaxis in patients with spinal cord injury: a prospective TRACK-SCI registry study.

OBJECTIVE: Venous thromboembolism (VTE) following traumatic spinal cord injury (SCI) is a significant clinical concern. This study sought to determine the incidence of VTE and hemorrhagic complications among patients with SCI who received low-molecular-weight heparin (LMWH) within 24 hours of injury or surgery and identify variables that predict VTE using the prospective Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database. METHODS: The TRACK-SCI database was queried for individuals with traumatic SCI from 2015 to 2022. Primary outcomes of interest included rates of VTE (including deep vein thrombosis [DVT] and pulmonary embolism [PE]) and in-hospital hemorrhagic complications that occurred after LWMH administration. Secondary outcomes included intensive care unit and hospital length of stay, discharge location type, and in-hospital mortality. RESULTS: The study cohort consisted of 162 patients with SCI. Fifteen of the 162 patients withdrew from the study, leading to loss of data for certain variables for these patients. One hundred thirty patients (87.8%) underwent decompression and/or fusion surgery for SCI. DVT occurred in 11 (7.4%) of 148 patients, PE in 9 (6.1%) of 148, and any VTE in 18 (12.2%) of 148 patients. The analysis showed that admission lower-extremity motor score (p = 0.0408), injury at the thoracic level (p = 0.0086), admission American Spinal Injury Association grade (p = 0.0070), and younger age (p = 0.0372) were significantly associated with VTE. There were 3 instances of postoperative spine surgery-related bleeding (2.4%) in the 127 patients who had spine surgery with bleeding complication data available, with one requiring return to surgery (0.8%). Thirteen (8.8%) of 147 patients had a bleeding complication not related to spine surgery. There were 2 gastrointestinal bleeds associated with nasogastric tube placement, 3 cases of postoperative non-spine-related surgery bleeding, and 8 cases of other bleeding complications (5.4%) not related to any surgery. CONCLUSIONS: Initiation of LMWH within 24 hours was associated with a low rate of spine surgery-related bleeding. Bleeding complications unrelated to SCI surgery still occur with LMWH administration. Because neurosurgical intervention is typically the limiting factor in initializing chemical DVT prophylaxis, many of these bleeding complications would have likely occurred regardless of the protocol.

Hypotension requiring vasopressor treatment and increased cardiac complications in elderly spinal cord injury patients: a prospective TRACK-SCI registry study.

OBJECTIVE: Increasing life expectancy has led to an older population. In this study, the authors analyzed complications and outcomes in elderly patients following spinal cord injury (SCI) using the established multi-institutional prospective study Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) database collected in the Department of Neurosurgical Surgery at the University of California, San Francisco. METHODS: TRACK-SCI was queried for elderly individuals (≥ 65 years of age) with traumatic SCI from 2015 to 2019. Primary outcomes of interest included total hospital length of stay, perioperative complications, postoperative complications, and in-hospital mortality. Secondary outcomes included disposition location, and neurological improvement based on the American Spinal Injury Association Impairment Scale (AIS) grade at discharge. Descriptive analysis, Fisher's exact test, univariate analysis, and multivariable regression analysis were performed. RESULTS: The study cohort consisted of 40 elderly patients. The in-hospital mortality rate was 10%. Every patient in this cohort experienced at least 1 complication, with a mean of 6.6 separate complications (median 6, mode 4). The most common complication categories were cardiovascular, with a mean of 1.6 complications (median 1, mode 1), and pulmonary, with a mean of 1.3 (median 1, mode 0) complications, with 35 patients (87.5%) having at least 1 cardiovascular complication and 25 (62.5%) having at least 1 pulmonary complication. Overall, 32 patients (80%) required vasopressor treatment for mean arterial pressure (MAP) maintenance goals. The use of norepinephrine correlated with increased cardiovascular complications. Only 3 patients (7.5%) of the total cohort had an improved AIS grade compared with their acute level at admission. CONCLUSIONS: Given the increased frequency of cardiovascular complications associated with vasopressor use in elderly SCI patients, caution is warranted when targeting MAP goals in these patients. A downward adjustment of blood pressure maintenance goals and prophylactic cardiology consultation to select the most appropriate vasopressor agent may be advisable for SCI patients ≥ 65 years of age.

Is the Centers for Medicare and Medicaid Services Hierarchical Condition Category Risk Adjustment Model Satisfactory for Quantifying Risk After Spine Surgery?

BACKGROUND: The Centers for Medicare and Medicaid Services (CMS) hierarchical condition category (HCC) coding is a risk adjustment model that allows for the estimation of risk-and cost-associated with health care provision. Current models may not include key factors that fully delineate the risk associated with spine surgery. OBJECTIVE: To augment CMS HCC risk adjustment methodology with socioeconomic data to improve its predictive capabilities for spine surgery. METHODS: The National Inpatient Sample was queried for spinal fusion, and the data was merged with county-level coverage and socioeconomic status variables obtained from the Brookings Institute. We predicted outcomes (death, nonroutine discharge, length of stay [LOS], total charges, and perioperative complication) with pairs of hierarchical, mixed effects logistic regression models-one using CMS HCC score alone and another augmenting CMS HCC scores with demographic and socioeconomic status variables. Models were compared using receiver operating characteristic curves. Variable importance was assessed in conjunction with Wald testing for model optimization. RESULTS: We analyzed 653 815 patients. Expanded models outperformed models using CMS HCC score alone for mortality, nonroutine discharge, LOS, total charges, and complications. For expanded models, variable importance analyses demonstrated that CMS HCC score was of chief importance for models of mortality, LOS, total charges, and complications. For the model of nonroutine discharge, age was the most important variable. For the model of total charges, unemployment rate was nearly as important as CMS HCC score. CONCLUSION: The addition of key demographic and socioeconomic characteristics substantially improves the CMS HCC risk-adjustment models when modeling spinal fusion outcomes. This finding may have important implications for payers, hospitals, and policymakers.

Expert-augmented automated machine learning optimizes hemodynamic predictors of spinal cord injury outcome.

Artificial intelligence and machine learning (AI/ML) is becoming increasingly more accessible to biomedical researchers with significant potential to transform biomedicine through optimization of highly-accurate predictive models and enabling better understanding of disease biology. Automated machine learning (AutoML) in particular is positioned to democratize artificial intelligence (AI) by reducing the amount of human input and ML expertise needed. However, successful translation of AI/ML in biomedicine requires moving beyond optimizing only for prediction accuracy and towards establishing reproducible clinical and biological inferences. This is especially challenging for clinical studies on rare disorders where the smaller patient cohorts and corresponding sample size is an obstacle for reproducible modeling results. Here, we present a model-agnostic framework to reinforce AutoML using strategies and tools of explainable and reproducible AI, including novel metrics to assess model reproducibility. The framework enables clinicians to interpret AutoML-generated models for clinical and biological verifiability and consequently integrate domain expertise during model development. We applied the framework towards spinal cord injury prognostication to optimize the intraoperative hemodynamic range during injury-related surgery and additionally identified a strong detrimental relationship between intraoperative hypertension and patient outcome. Furthermore, our analysis captured how evolving clinical practices such as faster time-to-surgery and blood pressure management affect clinical model development. Altogether, we illustrate how expert-augmented AutoML improves inferential reproducibility for biomedical discovery and can ultimately build trust in AI processes towards effective clinical integration.

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.

Appendicular Fracture and Polytrauma Correlate with Outcome of Spinal Cord Injury: A Transforming Research and Clinical Knowledge in Spinal Cord Injury Study.

Spinal cord injuries (SCIs) frequently occur in combination with other major organ injuries, such as traumatic brain injury (TBI) and injuries to the chest, abdomen, and musculoskeletal system (e.g., extremity, pelvic, and spine fractures). However, the effects of appendicular fractures on SCI recovery are poorly understood. We investigated whether the presence of SCI-concurrent appendicular fractures is predictive of a less robust SCI recovery. Patients enrolled in the Transforming Research and Clinical Knowledge in SCI (TRACK-SCI) prospective cohort study were identified and included in this secondary analysis study. Inclusion criteria resulted in 147 patients, consisting of 120 with isolated SCIs and 27 with concomitant appendicular fracture. The primary outcome was American Spinal Injury Association (ASIA) Impairment Scale (AIS) neurological grades at hospital discharge. Secondary outcomes included hospital length of stay, intensive care unit (ICU) length of stay, and AIS grade improvement during hospitalization. Multivariable binomial logistical regression analyses assessed whether SCI-concomitant appendicular fractures associate with SCI function and secondary outcomes. These analyses were adjusted for age, gender, injury severity, and non-fracture polytrauma. Appendicular fractures were associated with more severe AIS grades at hospital discharge, though covariate adjustments diminished statistical significance of this effect. Notably, non-fracture injuries to the chest and abdomen were influential covariates. Secondary analyses suggested that appendicular fractures also increased hospital length of stay. Our study indicated that SCI-associated polytrauma is important for predicting SCI functional outcomes. Further statistical evaluation is required to disentangle the effects of appendicular fractures, non-fracture solid organ injury, and SCI physiology to improve health outcomes among SCI patients.

Topological network analysis of patient similarity for precision management of acute blood pressure in spinal cord injury.

Background: Predicting neurological recovery after spinal cord injury (SCI) is challenging. Using topological data analysis, we have previously shown that mean arterial pressure (MAP) during SCI surgery predicts long-term functional recovery in rodent models, motivating the present multicenter study in patients. Methods: Intra-operative monitoring records and neurological outcome data were extracted (n = 118 patients). We built a similarity network of patients from a low-dimensional space embedded using a non-linear algorithm, Isomap, and ensured topological extraction using persistent homology metrics. Confirmatory analysis was conducted through regression methods. Results: Network analysis suggested that time outside of an optimum MAP range (hypotension or hypertension) during surgery was associated with lower likelihood of neurological recovery at hospital discharge. Logistic and LASSO (least absolute shrinkage and selection operator) regression confirmed these findings, revealing an optimal MAP range of 76-[104-117] mmHg associated with neurological recovery. Conclusions: We show that deviation from this optimal MAP range during SCI surgery predicts lower probability of neurological recovery and suggest new targets for therapeutic intervention. Funding: NIH/NINDS: R01NS088475 (ARF); R01NS122888 (ARF); UH3NS106899 (ARF); Department of Veterans Affairs: 1I01RX002245 (ARF), I01RX002787 (ARF); Wings for Life Foundation (ATE, ARF); Craig H. Neilsen Foundation (ARF); and DOD: SC150198 (MSB); SC190233 (MSB).

Spinal cord injury is a devastating condition that involves damage to the nerve fibers connecting the brain with the spinal cord, often leading to permanent changes in strength, sensation and body functions, and in severe cases paralysis. Scientists around the world work hard to find ways to treat or even repair spinal cord injuries but few patients with complete immediate paralysis recover fully. Immediate paralysis is caused by direct damage to neurons and their extension in the spinal cord. Previous research has shown that blood pressure regulation may be key in saving these damaged neurons, as spinal cord injuries can break the communication between nerves that is involved in controlling blood pressure. This can lead to a vicious cycle of dysregulation of blood pressure and limit the supply of blood and oxygen to the damaged spinal cord tissue, exacerbating the death of spinal neurons. Management of blood pressure is therefore a key target for spinal cord injury care, but so far, the precise thresholds to enable neurons to recover are poorly understood. To find out more, Torres-Espin, Haefeli et al. used machine learning software to analyze previously recorded blood pressure and heart rate data obtained from 118 patients that underwent spinal cord surgery after acute spinal cord injury. The analyses revealed that patients who suffered from either low or high blood pressure during surgery had poorer prospects of recovery. Statistical models confirming these findings showed that the optimal blood pressure range to ensure recovery lies between 76 to 104-117 mmHg. Any deviation from this narrow window would dramatically worsen the ability to recover. These findings suggests that dysregulated blood pressure during surgery affects to odds of recovery in patients with a spinal cord injury. Torres-Espin, Haefeli et al. provide specific information that could improve current clinical practice in trauma centers. In the future, such machine learning tools and models could help develop real-time models that could predict the likelihood of a patient's recovery following spinal cord injury and related neurological conditions.

Single versus dual operative spine fractures in ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis, the most common spondyloarthritis, fuses individual spinal vertebrae into long segments. The unique biomechanics of the ankylosed spine places patients at unusually high risk for unstable fractures secondary to low-impact mechanisms. These injuries are unique within the spine trauma population and necessitate thoughtful management. Therefore, the authors aimed to present a richly annotated data set of operative AS spine fractures with a significant portion of patients with simultaneous dual noncontiguous fractures. METHODS: Patients with ankylosing spondylitis with acute fractures who received operative management between 2012 and 2020 were reviewed. Demographic, admission, surgical, and outcome parameters were retrospectively collected and reviewed. RESULTS: In total, 29 patients were identified across 30 different admissions. At admission, the mean age was 71.7 ± 11.8 years. The mechanism of injury in 77% of the admissions was a ground-level fall; 30% also presented with polytrauma. Of admissions, 50% were patient transfers from outside hospitals, whereas the other half presented primarily to our emergency departments. Fifty percent of patients sustained a spinal cord injury, and 35 operative fractures were identified and treated in 32 surgeries. The majority of fractures clustered around the cervicothoracic (C4-T1, 48.6%) and thoracolumbar (T8-L3, 37.11%) junctions. Five patients (17.2%) had simultaneous dual noncontiguous operative fractures; these patients were more likely to have presented with a higher-energy mechanism of injury such as a bicycle or motor vehicle accident compared with patients with a single operative fracture (60% vs 8%, p = 0.024). On preoperative MRI, 56.3% of the fractures had epidural hematomas (EDHs); 25% were compressive of the underlying neural elements, which dictated the number of laminectomy levels performed (no EDH, 2.1 ± 2.36; noncompressive EDH, 2.1 ± 1.85; and compressive EDH, 7.4 ± 4 [p = 0.003]). The mean difference in instrumented levels was 8.7 ± 2.6 with a mean estimated blood loss (EBL) of 1183 ± 1779.5 mL. Patients on a regimen of antiplatelet therapy had a significantly higher EBL (2635.7 mL vs 759.4 mL, p = 0.015). Overall, patients had a mean hospital length of stay of 15.2 ± 18.5 days; 5 patients died during the same admission or after transfer to an outside hospital. Nine of 29 patients (31%) had died by the last follow-up (the mean follow-up was 596.3 ± 878.9 days). CONCLUSIONS: Patients with AS who have been found to have unstable spine fractures warrant a thorough diagnostic evaluation to identify secondary fractures as well as compressive EDHs. These patients experienced prolonged inpatient hospitalizations with significant morbidity and mortality.

The Morbidity and Mortality of Surgery for Traumatic Brain Injury in Geriatric Patients: A Study of Over 100 000 Patient Cases.

BACKGROUND: Geriatric patients have the highest rates of Traumatic Brain Injury (TBI)-related hospitalization and death. This contributes to an assumption of futility in aggressive management in this population. OBJECTIVE: To evaluate the effect of surgical intervention on the morbidity and mortality of geriatric patients with TBI. METHODS: A retrospective analysis of patients ≥80 yr old with TBI from 2003 to 2016 was performed using the National Trauma Data Bank. Univariate and multivariate analyses were performed to compare outcomes between surgery and nonsurgery groups. RESULTS: A total of 127 129 patient incidents were included: 121 185 (95.3%) without surgery and 5944 (4.7%) with surgery. The surgical group was slightly younger (84.0 vs 84.3, P < .001) and predominantly male (60.2% vs 44.4%, P < .001). Mean emergency department (ED) Glasgow Coma Scale (GCS) was lower in surgical patients (12.4 vs 13.7, P < .001). Complications (OR = 1.91, CI:1.80-2.02, P < .001) and hospital length of stay (LOS, ß = 5.25, CI:5.08-5.42, P < .001) were independently associated with surgery. Intensive care unit (ICU) LOS (ß = 3.19, CI:3.05-3.34, P < .001), ventilator days (ß = 1.57, CI:1.22-1.92, P < .001), and reduced discharge home (OR = 0.434, CI:0.400-0.470, P < .001) were also independently associated with surgery. However, surgery was not independently associated with mortality on multivariate analysis (OR = 1.03, CI:0.955-1.12, P = .423). Recursive partitioning analysis identified ED GCS and injury severity score (ISS) as prognosticators of mortality following surgical intervention. CONCLUSION: Surgical treatment of geriatric patients with TBI is associated with increased complications, hospital LOS, ICU LOS, and ventilator days as well as reduced discharge to home. However, surgery is not associated with increased mortality. ISS and ED GCS are prognosticators of mortality following surgical intervention.

Telemedicine in Neurosurgery: Standardizing the Spinal Physical Examination Using A Modified Delphi Method.

OBJECTIVE: The use of telemedicine has dramatically increased due to the coronavirus disease 2019 pandemic. Many neurosurgeons are now using telemedicine technologies for preoperative evaluations and routine outpatient visits. Our goal was to standardize the telemedicine motor neurologic examination, summarize the evidence surrounding clinical use of telehealth technologies, and discuss financial and legal considerations. METHODS: We identified a 12-member panel composed of spine surgeons, fellows, and senior residents at a single institution. We created an initial telehealth strength examination protocol based on published data and developed 10 agree/disagree statements summarizing the protocol. A blinded Delphi method was utilized to build consensus for each statement, defined as > 80% agreement and no significant disagreement using a 2-way binomial test (significance threshold of p < 0.05). Any statement that did not meet consensus was edited and iteratively resubmitted to the panel until consensus was achieved. In the final round, the panel was unblinded and the protocol was finalized. RESULTS: After the first round, 4/10 statements failed to meet consensus ( < 80% agreement, and p = 0.031, p = 0.031, p = 0.003, and p = 0.031 statistical disagreement, respectively). The disagreement pertained to grading of strength of the upper (3/10 statements) and lower extremities (1/10 statement). The amended statements clarified strength grading, achieved consensus ( > 80% agreement, p > 0.05 disagreement), and were used to create the final telehealth strength examination protocol. CONCLUSION: The resulting protocol was used in our clinic to standardize the telehealth strength examination. This protocol, as well as our summary of telehealth clinical practice, should aid neurosurgical clinics in integrating telemedicine modalities into their practice.

Elderly traumatic central cord syndrome in the USA: a review of management and outcomes.

INTRODUCTION: As the incidence of elderly spinal cord injury rises, improved understanding of risk profiles and outcomes is needed. This review summarizes clinical characteristics, management, and outcomes specific to the elderly (≥65-years) with acute traumatic central cord syndrome in the USA. EVIDENCE AQUISITION: Literature review of the PubMed, Embase, and CINAHL databases (01/2007-03/2020) regarding elderly subjects with acute traumatic central cord syndrome. EVIDENCE SYNTHESIS: Nine studies met inclusion criteria. Acute traumatic central cord syndrome was more common among married (50%), Caucasian (22-71%) males (63-86%) with an annual income <40,999 USA dollars (30%). Mechanisms consisted predominantly of traumatic falls (32-55%) and motor vehicle collisions (15-34%), with admission American Spinal Injury Association Impairment Scale grades D (25-79%) and C (21-51%). Mortality was 2-3%. American Spinal Injury Association Impairment Scale motor score, maximum canal compromise, and extent of parenchymal damage were predictors of one-year recovery. Greater comorbidities (heart failure, weight loss, coagulopathy, diabetes), lower income (<51,000 USA dollars), and age ≥80 were predictors of mortality. A substantial cohort underwent surgery (40-45%). Elderly patients were less likely to receive surgical intervention, and surgery timing had variable effects on recovery. CONCLUSIONS: Elderly patients with acute traumatic central cord syndrome are uniquely at risk due to cumulative comorbidities, protracted recovery times, and unclear effects of surgical timing on outcomes. Prospective research should focus on validating age-specific risk factors, formalizing surgical indications, and delineating the impact of time to surgery on acute and long-term outcomes for this condition.

The Natural History of Spinal Cord Injury.

The natural history of spinal cord injury is in a state of flux. Our knowledge about the prevalence, epidemiology, and natural history spinal cord injury is in evolution. In this article, we summarize these considerations to provide a state-of-the-art synopsis of the neurologic outcomes of this condition.

Diagnostic blood RNA profiles for human acute spinal cord injury.

Diagnosis of spinal cord injury (SCI) severity at the ultra-acute stage is of great importance for emergency clinical care of patients as well as for potential enrollment into clinical trials. The lack of a diagnostic biomarker for SCI has played a major role in the poor results of clinical trials. We analyzed global gene expression in peripheral white blood cells during the acute injury phase and identified 197 genes whose expression changed after SCI compared with healthy and trauma controls and in direct relation to SCI severity. Unsupervised coexpression network analysis identified several gene modules that predicted injury severity (AIS grades) with an overall accuracy of 72.7% and included signatures of immune cell subtypes. Specifically, for complete SCIs (AIS A), ROC analysis showed impressive specificity and sensitivity (AUC: 0.865). Similar precision was also shown for AIS D SCIs (AUC: 0.938). Our findings indicate that global transcriptomic changes in peripheral blood cells have diagnostic and potentially prognostic value for SCI severity.

Hospital complications and costs of spinal arteriovenous malformations in the United States from 2002-2014.

BACKGROUND: Spinal arteriovenous malformations (AVMs) are rare disease entities with significant morbidity if untreated. Risk factors of complications, hospitalization and costs-of-care remain in need of characterization. METHODS: Using the National Inpatient Sample years 2002-2014, adult subjects with spinal AVMs who underwent either laminectomy with lesion excision or endovascular embolization were extracted using ICD-9-CM diagnostic code 747.82. Predictors of inpatient complications, hospital length of stay (HLOS), and discharge home were evaluated using multivariable regression. Cost was evaluated using inflation-adjusted healthcare cost [charge*(cost/charge ratio)]. Mean differences (B), odds ratios (OR) and 95% CIs are reported. Significance was assessed at P<0.001. RESULTS: In 2546 weighted admissions, age was 54.4±16.5-years (laminectomy: 70.0%, embolization: 30.0%). Fifteen percent suffered inpatient complications. Cost of hospitalization was $ 41216±38511 and was elevated for subjects with complications ($67571±2636, vs. no complications: $36562±723, P<0.001). Increased costs for categories of complications ranged from $ 16525 (renal/urinary) to $62246 (thromboembolism). In surgical subjects, complications were more costly ($ 69761±2896, vs. no complications: 36520±809, P<0.001). On multivariable analysis, major/extreme disease severity and major/extreme mortality risk were associated with increased complications and HLOS (P<0.001). Elective admissions had shorter HLOS (B=-4.3-days, [-4.8, -3.8], P<0.001) and higher odds of discharge home (OR=2.6 [2.1-3.2], P<0.001). Laminectomy (vs. embolization) was associated with complications (OR=2.6, 95% CI [1.7-3.8], P<0.001), HLOS (B=3.4-days [2.9-4.0], P<0.001), and decreased discharge home (OR=0.3 [0.2-0.4], P<0.001). CONCLUSIONS: In spinal AVMs, high disease severity, non-elective admissions, and surgery are associated with complications, HLOS, and discharge to a non-home facility. Costs are elevated in patients suffering complications. Future studies are warranted.

Anterior Lumbar Interbody Fusion With Cage Retrieval for the Treatment of Pseudarthrosis After Transforaminal Lumbar Interbody Fusion: A Single-Institution Case Series.

BACKGROUND: The treatment of pseudarthrosis after transforaminal lumbar interbody fusion (TLIF) can be challenging, particularly when anterior column reconstruction is required. There are limited data on TLIF cage removal through an anterior approach. OBJECTIVE: To assess the safety and efficacy of anterior lumbar interbody fusion (ALIF) as a treatment for pseudarthrosis after TLIF. METHODS: ALIFs performed at a single academic medical center were reviewed to identify cases performed for the treatment of pseudarthrosis after TLIF. Patient demographics, surgical characteristics, perioperative complications, and 1-yr radiographic data were collected. RESULTS: A total of 84 patients were identified with mean age of 59 yr and 37 women (44.0%). A total of 16 patients (19.0%) underwent removal of 2 interbody cages for a total of 99 implants removed with distribution as follows: 1 L2/3 (0.9%), 6 L3/4 (5.7%), 37 L4/5 (41.5%), and 55 L5/S1 (51.9%). There were 2 intraoperative venous injuries (2.4%) and postoperative complications were as follows: 7 ileus (8.3%), 5 wound-related (6.0%), 1 rectus hematoma (1.1%), and 12 medical complications (14.3%), including 6 pulmonary (7.1%), 3 cardiac (3.6%), and 6 urinary tract infections (7.1%). Among 58 patients with at least 1-yr follow-up, 56 (96.6%) had solid fusion. There were 5 cases of subsidence (6.0%), none of which required surgical revision. Two patients (2.4%) required additional surgery at the level of ALIF for pseudarthrosis. CONCLUSION: ALIF is a safe and effective technique for the treatment of TLIF cage pseudarthrosis with a favorable risk profile.

Does state malpractice environment affect outcomes following spinal fusions? A robust statistical and machine learning analysis of 549,775 discharges following spinal fusion surgery in the United States.

OBJECTIVE: Spine surgery is especially susceptible to malpractice claims. Critics of the US medical liability system argue that it drives up costs, whereas proponents argue it deters negligence. Here, the authors study the relationship between malpractice claim density and outcomes. METHODS: The following methods were used: 1) the National Practitioner Data Bank was used to determine the number of malpractice claims per 100 physicians, by state, between 2005 and 2010; 2) the Nationwide Inpatient Sample was queried for spinal fusion patients; and 3) the Area Resource File was queried to determine the density of physicians, by state. States were categorized into 4 quartiles regarding the frequency of malpractice claims per 100 physicians. To evaluate the association between malpractice claims and death, discharge disposition, length of stay (LOS), and total costs, an inverse-probability-weighted regression-adjustment estimator was used. The authors controlled for patient and hospital characteristics. Covariates were used to train machine learning models to predict death, discharge disposition not to home, LOS, and total costs. RESULTS: Overall, 549,775 discharges following spinal fusions were identified, with 495,640 yielding state-level information about medical malpractice claim frequency per 100 physicians. Of these, 124,425 (25.1%), 132,613 (26.8%), 130,929 (26.4%), and 107,673 (21.7%) were from the lowest, second-lowest, second-highest, and highest quartile states, respectively, for malpractice claims per 100 physicians. Compared to the states with the fewest claims (lowest quartile), surgeries in states with the most claims (highest quartile) showed a statistically significantly higher odds of a nonhome discharge (OR 1.169, 95% CI 1.139-1.200), longer LOS (mean difference 0.304, 95% CI 0.256-0.352), and higher total charges (mean difference [log scale] 0.288, 95% CI 0.281-0.295) with no significant associations for mortality. For the machine learning models-which included medical malpractice claim density as a covariate-the areas under the curve for death and discharge disposition were 0.94 and 0.87, and the R2 values for LOS and total charge were 0.55 and 0.60, respectively. CONCLUSIONS: Spinal fusion procedures from states with a higher frequency of malpractice claims were associated with an increased odds of nonhome discharge, longer LOS, and higher total charges. This suggests that medicolegal climate may potentially alter practice patterns for a given spine surgeon and may have important implications for medical liability reform. Machine learning models that included medical malpractice claim density as a feature were satisfactory in prediction and may be helpful for patients, surgeons, hospitals, and payers.

Injury volume extracted from MRI predicts neurologic outcome in acute spinal cord injury: A prospective TRACK-SCI pilot study.

Conventional MRI measures of traumatic spinal cord injury severity largely rely on 2-dimensional injury characteristics such as intramedullary lesion length and cord compression. Recent advances in spinal cord (SC) analysis have led to the development of a robust anatomic atlas incorporated into an open-source platform called the Spinal Cord Toolbox (SCT) that allows for quantitative volumetric injury analysis. In the current study, we evaluate the prognostic value of volumetric measures of spinal cord injury on MRI following registration of T2-weighted (T2w) images and segmented lesions from acute SCI patients with a standardized atlas. This IRB-approved prospective cohort study involved the image analysis of 60 blunt cervical SCI patients enrolled in the TRACK-SCI clinical research protocol. Axial T2w MRI data obtained within 24 h of injury were processed using the SCT. Briefly, SC MRIs were automatically segmented using the sct_deepseg_sc tool in the SCT and segmentations were manually corrected by a neuro-radiologist. Lesion volume data were used as predictor variables for correlation with lower extremity motor scores at discharge. Volumetric MRI measures of T2w signal abnormality comprising the SCI lesion accurately predict lower extremity motor scores at time of patient discharge. Similarly, MRI measures of injury volume significantly correlated with motor scores to a greater degree than conventional 2-D metrics of lesion size. The volume of total injury and of injured spinal cord motor regions on T2w MRI is significantly and independently associated with neurologic outcome at discharge after injury.