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.

Association of CSF and Serum Neurofilament Light and Glial Fibrillary Acidic Protein, Injury Severity, and Outcome in Spinal Cord Injury.

BACKGROUND AND OBJECTIVES: Traumatic spinal cord injury (SCI) is highly heterogeneous, and tools to better delineate pathophysiology and recovery are needed. Our objective was to profile the response of 2 biomarkers, neurofilament light (NF-L) and glial fibrillary acidic protein (GFAP), in the serum and CSF of patients with acute SCI to evaluate their ability to objectively characterize injury severity and predict neurologic recovery. METHODS: Blood and CSF samples were obtained from prospectively enrolled patients with acute SCI through days 1-4 postinjury, and the concentration of NF-L and GFAP was quantified using Simoa technology. Neurologic assessments defined the ASIA Impairment Scale (AIS) grade and motor score (MS) at presentation and 6 months postinjury. RESULTS: One hundred eighteen patients with acute SCI (78 AIS A, 20 AIS B, and 20 AIS C) were enrolled, with 113 (96%) completing 6-month follow-up. NF-L and GFAP levels were strongly associated between paired serum and CSF specimens, were both increased with injury severity, and distinguished among baseline AIS grades. Serum NF-L and GFAP were significantly (p = 0.02 to <0.0001) higher in AIS A patients who did not improve at 6 months, predicting AIS grade conversion with a sensitivity and specificity (95% CI) of 76% (61, 87) and 77% (55, 92) using NF-L and 72% (57, 84) and 77% (55, 92) using GFAP at 72 hours, respectively. Independent of clinical baseline assessment, a serum NF-L threshold of 170 pg/mL at 72 hours predicted those patients who would be classified as motor complete (AIS A/B) compared with motor incomplete (AIS C/D) at 6 months with a sensitivity of 87% (76, 94) and specificity of 84% (69, 94); a serum GFAP threshold of 13,180 pg/mL at 72 hours yielded a sensitivity of 90% (80, 96) and specificity of 84% (69, 94). DISCUSSION: The potential for NF-L and GFAP to classify injury severity and predict outcome after acute SCI will be useful for patient stratification and prognostication in clinical trials and inform communication of prognosis. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that higher serum NF-L and GFAP are associated with worse neurological outcome after acute SCI. TRIAL REGISTRATION INFORMATION: Registered on ClinicalTrials.gov: NCT00135278 (March 2006) and NCT01279811 (January 2012).

Secondary infections modify the overall course of hospitalized patients with COVID-19: a retrospective study from a network of hospitals across North India.

Objective: To gain better insight into the extent of secondary bacterial and fungal infections in hospitalized patients in India, and to assess how these alter the course of coronavirus disease 2019 (COVID-19) so that control measures can be suggested. Methods: In this retrospective, multicentre study, the data of all patients who tested positive for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) on reverse transcriptase polymerase chain reaction (RT-PCR), admitted to hospital between March 2020 and July 2021, were accessed from the electronic health records of a network of 10 hospitals across five states in North India. Results: Of 19,852 patients testing positive for SARS-CoV-2 on RT-PCR and admitted to the study hospitals during the study period, 1940 (9.8%) patients developed secondary infections (SIs). Patients with SIs were, on average, 8 years older than patients without SIs (median age 62.6 vs 54.3 years; P<0.001). The risk of SIs was significantly (P<0.001) associated with age, severity of disease at admission, diabetes, admission to the intensive care unit (ICU), and ventilator use. The most common site of infection was urine (41.7%), followed by blood (30.8%) and sputum/bronchoalveolar lavage/endotracheal fluid (24.8%); the least common was pus/wound discharge (2.6%). Gram-negative bacilli (GNB) were the most common organisms (63.2%), followed by Gram-positive cocci (GPC) (19.6%) and fungi (17.3%). Most patients with SIs were on multiple antimicrobials. The most commonly used antibiotics against GNB were beta-lactam/beta-lactamase inhibitors (76.9%), carbapenems (57.7%), cephalosporins (53.9%), and antibiotics against carbapenem-resistant Enterobacteriaceae (47.1%). Empirical use of antibiotics against GPC was seen in 58.9% of patients with SIs, and empirical use of antifungals was observed in 56.9% of patients with SIs. The average length of hospital stay for patients with SIs was almost twice as long as that of patients without SIs (median 13 vs 7 days). Overall mortality among patients with SIs (40.3%) was more than eight times higher than that among patients without SIs (4.6%). Only 1.2% of patients with SIs with mild COVID-19 at admission died, compared with 17.5% of those with moderate COVID-19 at admission and 58.5% of those with severe COVID-19 at admission (P<0.001). The mortality rate was highest in patients with bloodstream infections (49.8%), followed by those with hospital-acquired pneumonia (47.9%), urinary tract infections (29.4%), and skin and soft tissue infections (29.4%). The mortality rate in patients with diabetes with SIs was 45.2%, compared with 34.3% in those without diabetes (P<0.001). Conclusions: SIs complicate the course of patients hospitalized with COVID-19. These patients tend to have a much longer hospital stay, a higher requirement for oxygen and ICU care, and a significantly higher mortality rate compared with those without SIs. The groups most vulnerable to SIs are patients with more severe COVID-19, elderly patients and patients with diabetes. Judicious empirical use of combination antimicrobials in these groups of vulnerable patients can save lives. It is desirable to have region- or country-specific guidelines for appropriate use of antibiotics and antifungals to prevent their overuse.

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.

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.

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.

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.

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.

Characterization of Hyperacute Neuropathic Pain after Spinal Cord Injury: A Prospective Study.

There is currently a lack of information regarding neuropathic pain in the very early stages of spinal cord injury (SCI). In the present study, neuropathic pain was assessed using the Douleur Neuropathique 4 Questions (DN4) for the patient's worst pain within the first 5 days of injury (i.e., hyperacute) and on follow-up at 3, 6, and 12 months. Within the hyperacute time frame (i.e., 5 days), at- and below-level neuropathic pain were reported as the worst pain in 23% (n = 18) and 5% (n = 4) of individuals with SCI, respectively. Compared to the neuropathic pain observed in this hyperacute setting, late presenting neuropathic pain was characterized by more intense painful electrical and cold sensations, but less itching sensations. Phenotypic differences between acute and late neuropathic pain support the incorporation of timing into a mechanism-based classification of neuropathic pain after SCI. The diagnosis of acute neuropathic pain after SCI is challenged by the presence of nociceptive and neuropathic pains, with the former potentially masking the latter. This may lead to an underestimation of the incidence of neuropathic pain during the very early, hyperacute time points post-injury. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT01279811) PERSPECTIVE: This article presents distinct pain phenotypes of hyperacute and late presenting neuropathic pain after spinal cord injury and highlights the challenges of pain assessments in the acute phase after injury. This information may be relevant to clinical trial design and broaden our understanding of neuropathic pain mechanisms after spinal cord injury.

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.

An updated management algorithm for incorporating minimally invasive techniques to treat thoracolumbar trauma.

OBJECTIVE: Minimally invasive surgery (MIS) techniques can effectively stabilize and decompress many thoracolumbar injuries with decreased morbidity and tissue destruction compared with open approaches. Nonetheless, there is limited direction regarding the breadth and limitations of MIS techniques for thoracolumbar injuries. Consequently, the objectives of this study were to 1) identify the range of current practice patterns for thoracolumbar trauma and 2) integrate expert opinion and literature review to develop an updated treatment algorithm. METHODS: A survey describing 10 clinical cases with a range of thoracolumbar injuries was sent to 12 surgeons with expertise in spine trauma. The survey results were summarized using descriptive statistics, along with the Fleiss kappa statistic of interrater agreement. To develop an updated treatment algorithm, the authors used a modified Delphi technique that incorporated a literature review, the survey results, and iterative feedback from a group of 14 spine trauma experts. The final algorithm represented the consensus opinion of that expert group. RESULTS: Eleven of 12 surgeons contacted completed the case survey, including 8 (73%) neurosurgeons and 3 (27%) orthopedic surgeons. For the 4 cases involving patients with neurological deficits, nearly all respondents recommended decompression and fusion, and the proportion recommending open surgery ranged from 55% to 100% by case. Recommendations for the remaining cases were heterogeneous. Among the neurologically intact patients, MIS techniques were typically recommended more often than open techniques. The overall interrater agreement in recommendations was 0.23, indicating fair agreement. Considering both literature review and expert opinion, the updated algorithm indicated that MIS techniques could be used to treat most thoracolumbar injuries. Among neurologically intact patients, percutaneous instrumentation without arthrodesis was recommended for those with AO Spine Thoracolumbar Classification System subtype A3/A4 (Thoracolumbar Injury Classification and Severity Score [TLICS] 4) injuries, but MIS posterior arthrodesis was recommended for most patients with AO Spine subtype B2/B3 (TLICS > 4) injuries. Depending on vertebral body integrity, anterolateral corpectomy or mini-open decompression could be used for patients with neurological deficits. CONCLUSIONS: Spine trauma experts endorsed a range of strategies for treating thoracolumbar injuries but felt that MIS techniques were an option for most patients. The updated treatment algorithm may provide a foundation for surgeons interested in safe approaches for using MIS techniques to treat thoracolumbar trauma.

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.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Perioperative Spine: Preoperative Pulmonary Evaluation and Optimization.

BACKGROUND: There are no current recommendations for preoperative pulmonary evaluation and management of patients undergoing elective spine surgery. OBJECTIVE: The aim of this guideline is to determine preoperative risk factors for perioperative and postoperative pulmonary adverse events and to determine the optimal preoperative evaluation and management of at-risk patients. METHODS: A systematic review of the literature was performed using the National Library of Medicine PubMed database and the Cochrane Library for studies relevant to postoperative pulmonary adverse events in patients undergoing spine surgery. Clinical studies evaluating preoperative patient risk factors and preoperative diagnostic and treatment interventions were selected for review. RESULTS: The literature search yielded 152 abstracts relevant to the PICO (patient/population, intervention, comparison, and outcomes) questions included in this chapter. The task force selected 65 articles for full-text review, and 24 were selected for inclusion in this systematic review. Twenty-three articles addressed preoperative patient risk factors. One article addressed preoperative diagnostic studies of pulmonary function. There were no studies meeting the inclusion criteria for preoperative pulmonary treatment. CONCLUSION: There is substantial evidence for multiple preoperative patient factors that predict an increased risk of a postoperative pulmonary adverse event. Individuals with these risk factors (functional dependence, advanced age [≥65 yr], chronic obstructive pulmonary disease, congestive heart failure, weight loss, and obstructive sleep apnea) who are undergoing spine surgery should be counseled regarding the potential increased risk of a perioperative and postoperative pulmonary adverse events. There is insufficient evidence to support any specific preoperative diagnostic test for predicting the risk of postoperative pulmonary adverse events or any treatment intervention that reduces risk. It is suggested, however, to consider appropriate preoperative pulmonary diagnostic testing and treatment to address active pulmonary symptoms of existing or suspected disease.The full guidelines can be accessed at https://www.cns.org/guidelines/browse-guidelines-detail/5-preoperative-pulmonary-evaluation-optimization.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Perioperative Spine: Preoperative Opioid Evaluation.

BACKGROUND: Opioid use disorders in the United States have rapidly increased, yet little is known about the relationship between preoperative opioid duration and dose and patient outcomes after spine surgery. Likewise, the utility of preoperative opioid weaning is poorly understood. OBJECTIVE: The purpose of this evidence-based clinical practice guideline is to determine if duration and dose of preoperative opioids or preoperative opioid weaning is associated with patient-reported outcomes or adverse events after elective spine surgery for degenerative conditions. METHODS: A systematic review of the literature was performed using the National Library of Medicine/PubMed database and Embase for studies relevant to opioid use among adult patients undergoing spine surgery. Clinical studies evaluating preoperative duration, dose, and opioid weaning and outcomes were selected for review. RESULTS: A total of 41 of 845 studies met the inclusion criteria and none were Level I evidence. The use of any opioids before surgery was associated with longer postoperative opioid use, and longer duration of opioid use was associated with worse outcomes, such as higher complications, longer length of stay, higher costs, and increased utilization of resources. There is insufficient evidence to support the efficacy of opioid weaning on postoperative opioid use, improving outcome, or reducing adverse events after spine surgery. CONCLUSION: This evidence-based clinical guideline provides Grade B recommendations that preoperative opioid use and longer duration of preoperative opioid use are associated with chronic postoperative opioid use and worse outcome after spine surgery. Insufficient evidence supports the efficacy of an opioid wean before spine surgery (Grade I).The full guidelines can be accessed at https://www.cns.org/guidelines/browse-guidelines-detail/1-preoperative-opioid-evaluation.

Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines for Perioperative Spine: Preoperative Osteoporosis Assessment.

BACKGROUND: Osteoporosis is a metabolic bone disease that commonly affects the elderly. Degenerative spinal disease that may require surgical intervention is also prevalent in this susceptible population. If undiagnosed or untreated before spine surgery, osteoporosis may result in an increased risk of postoperative adverse events. Nontreatment of osteoporosis preoperatively may be related to a poor understanding of bone physiology, a lack of standardized treatment algorithms, limited cost-effective interventions, and reluctance by spine surgeons to be the primary provider of osteoporosis management. OBJECTIVE: The objective of this evidence-based review is to develop guidelines for the preoperative assessment and treatment of osteoporosis in patients undergoing spine surgery. METHODS: A systematic review of the literature was performed using the National Library of Medicine/PubMed database and Embase for studies relevant to preoperative diagnostic studies that predict increased risk of osteoporosis-related postoperative adverse events and whether the preoperative treatment of low bone mineral density (BMD) in patients with osteoporosis improves outcome. RESULTS: Out of 281 studies, 17 met the inclusion criteria and were included for systematic review. The task force affirmed a Grade B recommendation that preoperative osteoporosis testing with a dual-energy X-ray absorptiometry scan (T-score < -2.5), a computed tomography scan (Hounsfield units <97.9), and serum vitamin D3 level (<20 ng/mL) predict an increased risk of osteoporosis-related adverse events after spine surgery. The task force determined a Grade B recommendation that preoperative osteoporosis treatment with teriparatide increases BMD, induces earlier and more robust fusion, and may improve select patient outcomes. There is insufficient evidence regarding preoperative treatment with bisphosphonates alone and postoperative outcome. CONCLUSION: This evidence-based clinical guideline provides a recommendation that patients with suspected osteoporosis undergo preoperative assessment and be appropriately counseled about the risk of postoperative adverse events if osteoporosis is confirmed. In addition, preoperative optimization of BMD with select treatments improves certain patient outcomes.The full guidelines can be accessed at https://www.cns.org/guidelines/browse-guidelines-detail/3-preoperative-osteoporosis-assessment.