Postoperative C5 Palsy after Anterior or Posterior Decompression for Degenerative Cervical Myelopathy: A Subgroup Analysis of the Multicenter, Prospective, Randomized, Phase III, CSM-Protect Clinical Trial.

STUDY DESIGN: Retrospective cohort study of prospectively accrued data. OBJECTIVE: To evaluate a large, prospective, multicentre dataset of surgically-treated DCM cases on the contemporary risk of C5 palsy with surgical approach. SUMMARY OF BACKGROUND DATA: The influence of surgical technique on postoperative C5 palsy after decompression for degenerative cervical myelopathy (DCM) is intensely debated. Comprehensive analyses are needed using contemporary data and accounting for covariates. METHODS: Patients with moderate to severe DCM were prospectively enrolled in the multicenter, randomized CSM-Protect clinical trial and underwent either anterior or posterior decompression between Jan 31, 2012, to May 16, 2017. The primary outcome was the incidence of postoperative C5 palsy, defined as onset of muscle weakness by at least one grade in manual muscle test at the C5 myotome with slight or absent sensory disruption after cervical surgery. Two comparative cohorts were made based on anterior or posterior surgical approach. Multivariate hierarchical mixed-effects logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI) for C5 palsy. RESULTS: A total of 283 patients were included, and 53.4% underwent posterior decompression. The total incidence of postoperative C5 palsy was 7.4% and was significantly higher in patients that underwent posterior decompression compared to anterior decompression (11.26% vs. 3.03%, P=0.008). After multivariable regression, posterior approach was independently associated with greater than four times the likelihood of postoperative C5 palsy (P=0.017). Rates of C5 palsy recovery were comparable between the two surgical approaches. CONCLUSION: The odds of postoperative C5 palsy are significantly higher after posterior decompression compared to anterior decompression for DCM. This may influence surgical decision-making when there is equipoise in deciding between anterior and posterior treatment options for DCM. LEVEL OF EVIDENCE: Therapeutic Level II.

A Clinical Practice Guideline for the Management of Patients With Acute Spinal Cord Injury: Recommendations on Hemodynamic Management.

STUDY DESIGN: Clinical practice guideline development following the GRADE process. OBJECTIVES: Hemodynamic management is one of the only available treatment options that likely improves neurologic outcomes in patients with acute traumatic spinal cord injury (SCI). Augmenting mean arterial pressure (MAP) aims to improve blood perfusion and oxygen delivery to the injured spinal cord in order to minimize secondary ischemic damage to neural tissue. The objective of this guideline was to update the 2013 AANS/CNS recommendations on the hemodynamic management of patients with acute traumatic SCI, acknowledging that much has been published in this area since its publication. Specifically, we sought to make recommendations on 1. The range of mean arterial pressure (MAP) to be maintained by identifying an upper and lower MAP limit; 2. The duration of such MAP augmentation; and 3. The choice of vasopressor. Additionally, we sought to make a recommendation on spinal cord perfusion pressure (SCPP) targets. METHODS: A multidisciplinary guideline development group (GDG) was formed that included health care professionals from a wide range of clinical specialities, patient advocates, and individuals living with SCI. The GDG reviewed the 2013 AANS/CNS guidelines and voted on whether each recommendation should be endorsed or updated. A systematic review of the literature, following PRISMA standards and registered in PROSPERO, was conducted to inform the guideline development process and address the following key questions: (i) what are the effects of goal-directed interventions to optimize spinal cord perfusion on extent of neurological recovery and rates of adverse events at any time point of follow-up? and (ii) what are the effects of particular monitoring techniques, perfusion ranges, pharmacological agents, and durations of treatment on extent of neurological recovery and rates of adverse events at any time point of follow-up? The GDG combined the information from this systematic review with their clinical expertise in order to develop recommendations on a MAP target range (specifically an upper and lower limit to target), the optimal duration for MAP augmentation, and the use of vasopressors or inotropes. Using methods outlined by the GRADE working group, recommendations were formulated that considered the balance of benefits and harms, financial impact, acceptability, feasibility and patient preferences. RESULTS: The GDG suggested that MAP should be augmented to at least 75-80 mmHg as the "lower limit," but not actively augmented beyond an "upper limit" of 90-95 mmHg in order to optimize spinal cord perfusion in acute traumatic SCI. The quality of the evidence around the "target MAP" was very low, and thus the strength of this recommendation is weak. For duration of hemodynamic management, the GDG "suggested" that MAP be augmented for a duration of 3-7 days. Again, the quality of the evidence around the duration of MAP support was very low, and thus the strength of this recommendation is also weak. The GDG felt that a recommendation on the choice of vasopressor or the use of SCPP targets was not warranted, given the dearth of available evidence. CONCLUSION: We provide new recommendations for blood pressure management after acute SCI that acknowledge the limitations of the current evidence on the relationship between MAP and neurologic recovery. It was felt that the low quality of existing evidence and uncertainty around the relationship between MAP and neurologic recovery justified a greater range of MAP to target, and for a broader range of days post-injury than recommended in previous guidelines. While important knowledge gaps still remain regarding hemodynamic management, these recommendations represent current perspectives on the role of MAP augmentation for acute SCI.

The Impact of Interhospital Transfer on the Extent of Neurological Recovery in Acute Traumatic Spinal Cord Injury: Analysis of a Prospective Multicenter Data Set in 970 Cases.

BACKGROUND AND OBJECTIVES: Interhospital transfer from community hospitals to centers specialized in managing traumatically injured individuals can strain patients, healthcare systems, and delay appropriate care. The purpose was to compare long-term neurological outcomes in transferred or directly admitted patients with traumatic spinal cord injury (SCI). METHODS: An ambispective cohort study was conducted using prospectively collected data (between 2005 and 2018) from 11 specialized level 1 trauma centers across the United States and Canada. All patients who underwent surgical management for SCI were included and placed into 2 comparison cohorts: (1) direct admission and (2) transfer from intermediate hospital. Outcomes were change in American Spinal Injury Association Impairment Scale grade and its components: upper-extremity motor, lower-extremity motor, pinprick, and light touch scores from baseline (assessed ≤72 hours after injury) to follow-up (12-52 weeks). Nearest-neighbor 1:1 propensity score matching between the transferred and directly admitted cohorts was performed. Paired analysis using McNemar's test and paired Student's t -test was used to determine the extent of the difference in neurological outcomes. RESULTS: Nine hundred seventy patients (55.5% male, 55.2 ± 18.9 years) with traumatic SCI were directly admitted to a specialized trauma center (N = 474, 48.9%) or transferred from an intermediate hospital (N = 496, 51.1%). After propensity score matching, 283 pairs were matched. Compared with a matched cohort of transferred patients, American Spinal Injury Association Impairment Scale grade improved more in directly admitted patients (56.2% vs 46.3%, P = .024), as did upper-extremity motor score (13.7 ± 12.8 vs 10.4 ± 11.5, P = .018) and light touch score (22.0 ± 29.7 vs 16.9 ± 26.6, P = .034). CONCLUSION: Patients with SCI directly admitted to specialized trauma centers have greater neurological recovery compared with patients transferred from an intermediate hospital. Feasibility of direct admission to a center specialized in the management of acute SCI through implementation of a standardized code program must be further investigated. LEVEL OF EVIDENCE: Therapeutic level II.

Influence of Body Mass Index on Surgical and Patient Outcomes for Cervical Spine Surgery.

STUDY DESIGN: Secondary analysis of prospectively collected registry. OBJECTIVE: We aim to investigate the effects of body mass index (BMI) on postsurgical cervical spine surgery outcomes and identify a potential substratification of obesity with worse outcomes. SUMMARY OF BACKGROUND DATA: The impact of BMI on cervical spine surgery is unknown, with controversial outcomes for patients high and low BMI. METHODS: The cervical spine Quality Outcomes Database was queried for a total of 10,381 patients who underwent single-stage cervical spine surgery. Patients were substratified into 6 groups based on BMI. Surgical outcomes, complications, hospitalization outcomes, and patient-reported outcomes for each cohort, including modified Japanese Orthopedic Association Score, Numeric Rating Scale arm pain, Numeric Rating Scale neck pain, Neck Disability Index, and EuroQol Health Survey, were assessed. Univariate analysis was performed for 3- and 12-month follow-up after surgical intervention. RESULTS: Obese patients (class I, II, and III) requiring spine surgery were statistically younger than nonobese patients and had higher rates of diabetes compared with normal BMI patients. The surgical length was found to be longer for overweight and all classes of obese patients ( P < 0.01). Class III obese patients had higher odds of postoperative complications. Patients with class II and III obesity had lower odds of achieving optimal modified Japanese Orthopedic Association Score at 3 months [OR = 0.8 (0.67-0.94), P < 0.01, OR = 0.68 (0.56-0.82), P < 0.001, respectively] and 12 months [OR = 0.82 (0.68-0.98), P = 0.03, OR = 0.79 (0.64-0.98), P = 0.03, respectively]. CONCLUSIONS: This study investigates the relationship between substratified BMI and postoperative outcomes of cervical spine surgery. Class II and III obese patients have substantially greater risk factors and poor outcomes postoperatively. In addition, low BMI also presents unique challenges for patients. Further research is needed for comprehensive analysis on outcomes of cervical spine surgery after correcting BMI.

Metal artifact reduction around cervical spine implant using diffusion tensor imaging at 3T: A phantom study.

PURPOSE: Diffusion MRI continues to play a key role in non-invasively assessing spinal cord integrity and pre-operative injury evaluation. However, post-operative Diffusion Tensor Imaging (DTI) acquisition of patients with metal implants results in severe geometric distortion. We propose and demonstrate a method to alleviate the technical challenges facing the acquisition of DTI on post-operative cases and longitudinal evaluation of therapeutics. MATERIAL AND METHODS: The described technique is based on the combination of the reduced Field-Of-View (rFOV) strategy and the phase segmented EPI, termed rFOV-PS-EPI. A custom-built phantom based on a cervical spine model with metal implants was used to collect DTI data at 3 Tesla scanner using: rFOV-PS-EPI, reduced Field-Of-View single-shot EPI (rFOV-SS-EPI), and conventional full FOV techniques including SS-EPI, PS-EPI, and readout-segmented EPI (RS-EPI). Geometric distortion, SNR, and signal void were assessed to evaluate images and compare the sequences. A two-sample t-test was performed with p-value of 0.05 or less to indicate statistical significance. RESULTS: The reduced FOV techniques showed better capability to reduce distortions compared to the Full FOV techniques. The rFOV-PS-EPI method provided DTI images of the phantom at the level of the hardware whereas the conventional rFOV-SS-EPI is useful only when the metal is approximately 20 mm away. In addition, compared to the rFOV-SS-EPI technique, the suggested approach produced smaller signal voids area as well as significantly reduced geometric distortion in Circularity (p < 0.005) and Eccentricity (p < 0.005) measurements. No statistically significant differences were found for these geometric distortion measurements between the rFOV-PS-EPI DTI sequence and conventional structural T2 images (p > 0.05). CONCLUSION: The combination of rFOV and a phase-segmented acquisition approach is effective for reducing metal-induced distortions in DTI scan on spinal cord with metal hardware at 3 T.

An Introduction to the North American Clinical Trials Network for Spinal Cord Injury Special Edition: Reflections on Accomplishments and a Look to the Future.

The North American Clinical Trials Network (NACTN) has been established as a network of translational clinical research centers focused on traumatic spinal cord injury (SCI) with the goals of facilitating clinical translational research, promotion of enhanced clinical care protocols including the principle of early surgery for SCI, and improving outcomes for individuals with acute SCI. Since its foundation in 2004 by Dr. Robert Grossman, NACTN has evolved into a powerful multi-stakeholder consortium of eight neurosurgical department faculties at university-affiliated institutions in the United States and Canada, a data management center, and a pharmacological center. To date, high-quality data from more than 1000 patients have been prospectively collected, providing us with a strong body of evidence surrounding SCI epidemiology, the natural history, and complications of acute and subacute SCI management. Key accomplishments of NACTN are summarized in this Focus issue. They include the launch, in collaboration with AO Spine, of the international, multi-center, placebo-controlled, Phase III Riluzole in Acute Spinal Cord Injury Study (RISCIS) that recruited 192 patients. While the primary analyses did not achieve the predetermined endpoint of efficacy for Riluzole, likely related to insufficient power, pre-planned secondary analyses demonstrated that all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with Riluzole showed significant gains in functional recovery. The Focus Issue also includes a detailed analysis of the pharmacokinetics and pharmacodynamics of riluzole in the setting of acute SCI (RISCIS-PK study). Additional achievements include key contributions to the evidence supporting the role of early surgery in acute SCI, and a better understanding of the impact of complications on the outcomes of SCI. Future directions of NACTN will build on past accomplishments and focus on enhanced collaborations with other SCI networks, advanced analytics to examine large datasets, and a greater focus on chronic SCI.

Secondary analysis of a James Lind Alliance priority setting partnership to facilitate knowledge translation in degenerative cervical myelopathy (DCM): insights from AO Spine RECODE-DCM.

OBJECTIVES: To explore whether a James Lind Alliance Priority Setting Partnership could provide insights on knowledge translation within the field of degenerative cervical myelopathy (DCM). DESIGN: Secondary analysis of a James Lind Alliance Priority Setting Partnership process for DCM. PARTICIPANTS AND SETTING: DCM stake holders, including spinal surgeons, people with myelopathy and other healthcare professionals, were surveyed internationally. Research suggestions submitted by stakeholders but considered answered were identified. Sampling characteristics of respondents were compared with the overall cohort to identify subgroups underserved by current knowledge translation. RESULTS: The survey was completed by 423 individuals from 68 different countries. A total of 22% of participants submitted research suggestions that were considered 'answered'. There was a significant difference between responses from different stakeholder groups (p<0.005). Spinal surgeons were the group which was most likely to submit an 'answered' research question. Respondents from South America were also most likely to submit 'answered' questions, when compared with other regions. However, there was no significant difference between responses from different stakeholder regions (p=0.4). CONCLUSIONS: Knowledge translation challenges exist within DCM. This practical approach to measuring knowledge translation may offer a more responsive assessment to guide interventions, complementing existing metrics.

Safety and Efficacy of Riluzole in Acute Spinal Cord Injury Study (RISCIS): A Multi-Center, Randomized, Placebo-Controlled, Double-Blinded Trial.

Riluzole is a sodium-glutamate antagonist that attenuates neurodegeneration in amyotrophic lateral sclerosis (ALS). It has shown favorable results in promoting recovery in pre-clinical models of traumatic spinal cord injury (tSCI) and in early phase clinical trials. This study aimed to evaluate the efficacy and safety of riluzole in acute cervical tSCI. An international, multi-center, prospective, randomized, double-blinded, placebo-controlled, adaptive, Phase III trial (NCT01597518) was undertaken. Patients with American Spinal Injury Association Impairment Scale (AIS) A-C, cervical (C4-C8) tSCI, and <12 h from injury were randomized to receive either riluzole, at an oral dose of 100 mg twice per day (BID) for the first 24 h followed by 50 mg BID for the following 13 days, or placebo. The primary efficacy end-point was change in Upper Extremity Motor (UEM) scores at 180 days. The primary efficacy analyses were conducted on an intention to treat (ITT) and completed cases (CC) basis. The study was powered at a planned enrolment of 351 patients. The trial began in October 2013 and was halted by the sponsor on May 2020 (and terminated in April 2021) in the face of the global COVID-19 pandemic. One hundred ninety-three patients (54.9% of the pre-planned enrolment) were randomized with a follow-up rate of 82.7% at 180 days. At 180 days, in the CC population the riluzole-treated patients compared with placebo had a mean gain of 1.76 UEM scores (95% confidence interval: -2.54-6.06) and 2.86 total motor scores (CI: -6.79-12.52). No drug-related serious adverse events were associated with the use of riluzole. Additional pre-planned sensitivity analyses revealed that in the AIS C population, riluzole was associated with significant improvement in total motor scores (estimate: standard error [SE] 8.0; CI 1.5-14.4) and upper extremity motor scores (SE 13.8; CI 3.1-24.5) at 6 months. AIS B patients had higher reported independence, measured by the Spinal Cord Independence Measure score (45.3 vs. 27.3; d: 18.0 CI: -1.7-38.0) and change in mental health scores, measured by the Short Form 36 mental health domain (2.01 vs. -11.58; d: 13.2 CI: 1.2-24.8) at 180 days. AIS A patients who received riluzole had a higher average gain in neurological levels at 6 months compared with placebo (mean 0.50 levels gained vs. 0.12 in placebo; d: 0.38, CI: -0.2-0.9). The primary analysis did not achieve the predetermined end-point of efficacy for riluzole, likely related to insufficient power. However, on pre-planned secondary analyses, all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with riluzole showed significant gains in functional recovery. The results of this trial may warrant further investigation to extend these findings. Moreover, guideline development groups may wish to assess the possible clinical relevance of the secondary outcome analyses, in light of the fact that SCI is an uncommon orphan disorder without an accepted neuroprotective treatment.

Mortality in ASIA Impairment Scale grade A to D Patients With Odontoid Fracture and Magnetic Resonance Imaging Evidence of Spinal Cord Injury.

Odontoid fractures are common, often presenting in the elderly after a fall and infrequently associated with traumatic spinal cord injury (tSCI). The goal of this study was to analyze predictors of mortality and neurological outcome when odontoid fractures were associated with signal change on magnetic resonance imaging (MRI) at admission. Over an 18-year period (2001-2019), 33 patients with odontoid fractures and documented tSCI on MRI were identified. Mean age was 65.3 years (standard deviation [SD] = 17.2), and 21 patients were male. The mechanism of injury was falls in 25 patients, motor vehicle accidents in 5, and other causes in 3. Mean Injury Severity Score (ISS) was 40.5 (SD = 30.2), Glasgow Coma Scale (GCS) score was 13 (SD = 3.4), and American Spinal Injury Association (ASIA) motor score (AMS) was 51.6 (SD = 42.7). ASIA Impairment Scale (AIS) grade was A, B, C, and D in 9, 2, 3, and 19 patients, respectively. Mean intramedullary lesion length was 32.3 mm (SD = 18.6). The odontoid peg was displaced ventral or dorsal in 15 patients. Twenty patients had surgical intervention: anterior odontoid screw fixation in 7 and posterior spinal fusion in 13. Eleven (33.3%) patients died in this series: withdrawal of medical care in 5; anoxic brain injury in 4; and failure of critical care management in 2. Univariate logistic regression indicated that GCS score (p < 0.014), AMS (p < 0.002), AIS grade (p < 0.002), and ISS (p < 0.009) were risk factors for mortality. Multi-variate regression analysis indicated that only AMS (p < 0.002) had a significant relationship with mortality when odontoid fracture was associated with tSCI (odds ratio, 0.963; 95% confidence interval, 0.941-0.986).

North American Clinical Trials Network for Spinal Cord Injury Registry: Methodology and Analysis.

The North American Clinical Trials Network (NACTN) for Spinal Cord Injury (SCI) is a consortium of neurosurgery departments at university affiliated hospitals with medical, nursing, and rehabilitation personnel who are skilled in the assessment, evaluation, and management of SCI. NACTN was established with the goal of consistently advancing the quality of life of people with SCI through clinical trials of new therapies that provide robust evidence of safety and effectiveness. A prospective multi-center Registry was created to collect the natural course of the acute traumatic SCI patient from time of injury to 12 months follow-up. NACTN's network of hospitals enrolls a significant number of patients, defines and adheres to standard protocols, and provides the infrastructure and highly skilled personnel to conduct trials of therapy for SCI. Registry data have been used by academic institutions and by the biotechnology and pharmaceutical sectors to create comparison datasets for Phase I clinical trials of new therapies.

Variability in Early Surgery for Acute Cervical Spinal Cord Injury Patients: An Opportunity for Enhanced Care Delivery.

Data supporting the benefits of early surgical intervention in acute spinal cord injury (SCI) is growing. For early surgery to be accomplished, understanding the causes of variabilities that effect the timing of surgery is needed to achieve this goal. The purpose of this analysis is to determine factors that affect the timing of surgery for acute cervical SCI within the North American Clinical Trials Network (NACTN) for SCI registry. Patients in the NACTN SCI registry from 2005 to 2019 with a cervical SCI, excluding acute traumatic central cord syndrome, were analyzed for time elapsed from injury to arrival to the hospital, and time to surgery. Two categories were defined: 1) Early Arrival with Early Surgery (EAES) commenced within 24 h of injury, and 2) Early Arrival but Delayed Surgery (EADS), with surgery occurring between 24 to 72 h post-injury. Patients' demographic features, initial clinical evaluation, medical comorbidities, neurological status, surgical intervention, complications, and outcome data were correlated with respect to the two arrival groups. Of the 222 acute cervical SCI patients undergoing surgery, 163 (73.4%) were EAES, and 59 (26.6%) were EADS. There was no statistical difference in arrival time between the EAES and EADS groups. There was a statistical difference in the median arrival time to surgery between the EAES group (9 h) compared with the EADS group (31 h; p < 0.05). There was no statistical difference in race, sex, age, mechanism of injury, Acute Physiologic Assessment and Chronic Health Evaluation (APACHE) II scores, or medical comorbidities between the two groups, but the EAES group did present with a significantly lower systolic blood pressure (p < 0.05). EADS patients were more likely to present as an American Spinal Injury Association Impairment Scale (AIS) D than EAES (p < 0.05). Early surgery was statistically more likely to occur if the injury occurred over the weekend (p < 0.05). There were variations in the rates of early surgery between the eight NACTN sites within the study, ranging from 57 to 100%. Of the 114 patients with 6-month outcome data, there was no significant change between the two groups regarding AIS grade change and motor/pin prick/light touch score recovery. A trend towards improved motor scores with early surgery was not statistically significant (p = 0.21). Although there is data that surgery within 24 h of injury improves outcomes and can be performed safely, there remain variations in care outside of clinical trials. In the present study of cervical SCI, NACTN achieved its goal of early surgery in 73.4% of patients from 2005-2019 who arrived within 24 h of their injury. Variability in achieving this goal was related to severity of neurological injury, the day of the week, and the treating NACTN center. Evaluating variations within our network improves understanding of potential systemic limitations and our decision-making process to accomplish the goal of early surgery.

Clinical Outcomes After Ultra-Early Cranioplasty Using Craniectomy Contour Classification as a Patient Selection Criterion.

BACKGROUND: Although not a technically difficult operation, cranioplasty is associated with high rates of complications. The optimal timing of cranioplasty to mitigate complications remains the subject of debate. OBJECTIVE: To report outcomes between patients undergoing cranioplasty at ultra-early (0-6 weeks), intermediate (6 weeks to 6 months), and late (>6 months) time frames. We report a novel craniectomy contour classification (CCC) as a radiographic parameter to assess readiness for cranioplasty. METHODS: A single-institution retrospective analysis of patients undergoing cranioplasty was performed. Patients were stratified into ultra-early (within 6 weeks of index craniectomy), intermediate (6 weeks to 6 months), and late (>6 months) cranioplasty cohorts. We have devised CCC scores, A, B, and C, based on radiographic criteria, where A represents those with a sunken brain/flap, B with a normal parenchymal contour, and C with "full" parenchyma. RESULTS: A total of 119 patients were included. There was no significant difference in postcranioplasty complications, including return to operating room ( P = .212), seizures ( P = .556), infection ( P = .140), need for shunting ( P = .204), and deep venous thrombosis ( P = .066), between the cohorts. Univariate logistic regression revealed that ultra-early cranioplasty was significantly associated with higher rate of functional independence at >6 months (odds ratio 4.32, 95% CI 1.39-15.13, P = .015) although this did not persist when adjusting for patient selection features (odds ratio 2.90, 95% CI 0.53-19.03, P = .234). CONCLUSION: In appropriately selected patients, ultra-early cranioplasty is not associated with increased rate of postoperative complications and is a viable option. The CCC may help guide decision-making on timing of cranioplasty.

Profiling Immunological Phenotypes in Individuals During the First Year After Traumatic Spinal Cord Injury: A Longitudinal Analysis.

Abstract Individuals with SCI are severely affected by immune system changes, resulting in increased risk of infections and persistent systemic inflammation. While recent data support that immunological changes after SCI differ in the acute and chronic phases of living with SCI, only limited immunological phenotyping in humans is available. To characterize dynamic molecular and cellular immune phenotypes over the first year, we assess RNA (bulk-RNA sequencing), protein, and flow cytometry (FACS) profiles of blood samples from 12 individuals with SCI at 0-3 days and at 3, 6, and 12 months post injury (MPI) compared to 23 uninjured individuals (controls). We identified 967 differentially expressed (DE) genes in individuals with SCI (FDR <0.001) compared to controls. Within the first 6 MPI we detected a reduced expression of NK cell genes, consistent with reduced frequencies of CD56bright, CD56dim NK cells present at 12 MPI. Over 6MPI, we observed increased and prolonged expression of genes associated with inflammation (e.g. HMGB1, Toll-like receptor signaling) and expanded frequencies of monocytes acutely. Canonical T-cell related DE genes (e.g. FOXP3, TCF7, CD4) were upregulated during the first 6 MPI and increased frequencies of activated T cells at 3-12 MPI. Neurological injury severity was reflected in distinct whole blood gene expression profiles at any time after SCI, verifying a persistent 'neurogenic' imprint. Overall, 2876 DE genes emerge when comparing motor complete to motor incomplete SCI (ANOVA, FDR <0.05), including those related to neutrophils, inflammation, and infection. In summary, we identify a dynamic immunological phenotype in humans, including molecular and cellular changes which may provide potential targets to reduce inflammation, improve immunity, or serve as candidate biomarkers of injury severity.

Does axial cervical pain improve with surgical fusion? A meta-analysis.

OBJECTIVE: Axial neck pain is a prevalent condition that causes significant morbidity and productivity loss. This study aimed to review the current literature and define the impact of surgical intervention on the management of cervical axial neck pain. METHODS: A search was conducted of three databases (Ovid MEDLINE, Embase, and Cochrane) for randomized controlled trials and cohort studies written in the English language with a minimum 6-month follow-up. The analysis was limited to patients with axial neck pain/cervical radiculopathy and preoperative/postoperative Neck Disability Index (NDI) and visual analog scale (VAS) scores. Literature reviews, meta-analyses, systematic reviews, surveys, and case studies were excluded. Two patient groups were analyzed: the arm pain predominant (pAP) cohort and the neck pain predominant (pNP) cohort. The pAP cohort had preoperative VAS neck scores that were lower than the arm scores, whereas the pNP cohort was defined as having preoperative VAS neck scores higher than the arm scores. A 30% reduction in patient-reported outcome measure (PROM) scores from the baseline represented the minimal clinically important difference (MCID). RESULTS: Five studies met the inclusion criteria, involving a total of 5221 patients. Patients with pAP showed a slightly higher percent reduction in PROM scores from baseline than those with pNP. The NDI reduction in patients with pNP was 41.35% (mean change in NDI score 16.3/mean baseline NDI score 39.42) (p < 0.0001), whereas those with pAP had a reduction of 45.12% (15.86/35.15) (p < 0.0001). Surgical improvement was slightly but similarly greater in pNP patients compared with pAP patients (16.3 vs 15.86 points, respectively; p = 0.3193). Regarding VAS scores, patients with pNP had a greater reduction in neck pain, with a change from baseline of 53.4% (3.60/6.74, p < 0.0001), whereas those with pAP had a change from baseline of 50.3% (2.46/4.89, p < 0.0001). The difference in VAS scores for neck pain improvement was significant (3.6 vs 2.46, p < 0.0134). Similarly, patients with pNP had a 43.6% (1.96/4.5) improvement in VAS scores for arm pain (p < 0.0001), whereas those with pAP had 66.12% (4.43/6.7) improvement (p < 0.0001). The VAS scores for arm pain were significantly greater in patients with pAP (4.43 vs 1.96 points, respectively; p < 0.0051). CONCLUSIONS: Overall, despite significant variations in the existing literature, there is mounting evidence that surgical intervention can lead to clinically meaningful improvements in patients with primary axial neck pain. The studies suggest that patients with pNP tend to have better improvement in neck pain than in arm pain. In both groups, the average improvements exceeded the MCID values and reached substantial clinical benefit in all studies. Further research is necessary to identify which patients and underlying pathologies will benefit most from surgical intervention for axial neck pain because it is a multifaceted condition with many causes.

Interhospital Transfer Delays Care for Spinal Cord Injury Patients: A Report from the North American Clinical Trials Network for Spinal Cord Injury.

Abstract The North America Clinical Trials Network (NACTN) for Spinal Cord Injury (SCI) is a consortium of tertiary medical centers that has maintained a prospective SCI registry since 2004, and it has espoused that early surgical intervention is associated with improved outcome. It has previously been shown that initial presentation to a lower acuity center and necessity of transfer to a higher acuity center reduce rates of early surgery. The NACTN database was evaluated to examine the association between interhospital transfer (IHT), early surgery, and outcome, taking into account distance traveled and site of origin for the patient. Data from a 15-year period of the NACTN SCI Registry were analyzed (years 2005-2019). Patients were stratified into transfers directly from the scene to a Level 1 trauma center (NACTN site) versus IHT from a Level 2 or 3 trauma facility. The main outcome was surgery within 24 hours of injury (yes/no), whereas secondary outcomes were length of stay, death, discharge disposition, and 6-month American Spinal Injury Association Impairment Scale (AIS) grade conversion. For the IHT patients, distance traveled for transfer was calculated by measuring the shortest distance between origin and NACTN hospital. Analysis was performed with Brown-Mood test and chi-square tests. Of 724 patients with transfer data, 295 (40%) underwent IHT and 429 (60%) were admitted directly from the scene of injury. Patients who underwent IHT were more likely to have a less severe SCI (AIS D; p = 0.002), have a central cord injury (p = 0.004), and have a fall as their mechanism of injury (p < 0.0001) than those directly admitted to an NACTN center. Of the 634 patients who had surgery, direct admission to an NACTN site was more likely to result in surgery within 24 hours compared with IHT patients (52% vs. 38%) (p < 0.0003). Median IHT distance was 28 miles (interquartile range [IQR] = 13-62 miles). There was no significant difference in death, length of stay, discharge to a rehab facility versus home, or 6-month AIS grade conversion rates between the two groups. Patients who underwent IHT to an NACTN site were less likely to have surgery within 24 hours of injury, compared with those directly admitted to the Level 1 trauma facility. Although there was no difference in mortality rates, length of stay, or 6-month AIS conversion between groups, patients with IHT were more likely be older with a less severe level of injury (AIS D). This study suggests there are barriers to timely recognition of SCI in the field, appropriate admission to a higher level of care after recognition, and challenges related to the management of individuals with less severe SCI.

Development of a comprehensive assessment tool to measure the quality of care for individuals with traumatic spinal cord injuries.

OBJECTIVE: To develop a comprehensive assessment tool to evaluate the Quality of Care (QoC) in managing individuals with traumatic spinal cord injuries (TSCI). METHOD: At first, the concepts of QoC for TSCI were identified by conducting a qualitative interview along with re-evaluation of the results of a published scoping review (conceptualization). After operationalization of indicators, they were valued by using the expert panel method. Afterward, the content validity index (CVI) and content validity ratio (CVR) were calculated and served as cut-offs for indicator selection. Then specific questions were developed for each indicator and classified into three categories: pre-hospital, in-hospital, and post-hospital. Data availability of the National Spinal Cord Injury Registry of Iran (NSCIR-IR) was subsequently used to design questions that represent indicators in an assessment tool format. The comprehensiveness of the tool was evaluated using a 4-item Likert scale by the expert panel. RESULT: Twelve experts participated in conceptualization and 11 experts participated in operationalization phase. Overall, 94 concepts for QoC were identified from published scoping review (87 items) and qualitative interviews (7 items). The process of operationalization and indicator selection led to the development of 27 indicators with acceptable content validity. Finally, the assessment tool contained three pre-hospital, twelve in-hospital, nine post-hospital, and three mixed indicators. Ninety-one percent of experts evaluated the entire tool as comprehensive. CONCLUSION: Our study presents a health-related QoC tool that contains a comprehensive set of indicators to assess the QoC for individuals with TSCI. However, this tool should be used in various situations to establish construct validity further.

Pressure ulcers and acute risk factors in individuals with traumatic spinal fractures with or without spinal cord injuries: A prospective analysis of the National Spinal Column/Cord Injury Registry of Iran (NSCIR-IR) data.

PURPOSE: To identify risk factors for developing pressure ulcers (PUs) in the acute care period of traumatic spinal fracture patients with or without spinal cord injuries (SCIs). METHODS: Data were collected prospectively in participating the National Spinal column/Cord Injury Registry of Iran (NSCIR-IR) from individuals with traumatic spinal fractures with or without SCIs, inclusive of the hospital stay from admission to discharge. Trained nursing staff examined the patients for the presence of PUs every 8 h during their hospital stay. The presence and grade of PUs were assessed according to the European Pressure Ulcer Advisory Panel classification. In addition to PU, following data were also extracted from the NSCIR-IR datasets during the period of 2015 - 2021: age, sex, Glasgow coma scale score at admission, having SCIs, marital status, surgery for a spinal fracture, American Spinal Injury Association impairment scale (AIS), urinary incontinence, level of education, admitted center, length of stay in the intensive care unit (ICU), hypertension, respiratory diseases, consumption of cigarettes, diabetes mellitus and length of stay in the hospital. Logistic regression models were used to estimate the unadjusted and adjusted odds ratio (OR) with 95% confidence intervals (CI). RESULTS: Altogether 2785 participants with traumatic spinal fractures were included. Among them, 87 (3.1%) developed PU during their hospital stay and 392 (14.1%) had SCIs. In the SCI population, 63 (16.1%) developed PU during hospital stay. Univariate logistic regression for the whole sample showed that marital status, having SCIs, urinary incontinence, level of education, treating center, number of days in the ICU, age, and Glasgow coma scale score were significant predictors for PUs. However, further analysis by multiple logistic regression only revealed the significant risk factors to be the treating center, marital status, having SCIs, and the number of days in the ICU. For the subgroup of individuals with SCIs, marital status, AIS, urinary incontinence, level of education, the treating center, the number of days in the ICU and the number of days in the hospital were significant predictors for PUs by univariate analysis. After adjustment in the multivariate model, the treating center, marital status (singles vs. marrieds, OR = 3.06, 95% CI: 1.55 - 6.03, p = 0.001), and number of days in the ICU (OR = 1.06, 95% CI: 1.04 - 1.09, p < 0.001) maintained significance. CONCLUSIONS: These data confirm that individuals with traumatic spinal fractures and SCIs, especially single young patients who suffer from urinary incontinence, grades A-D by AIS, prolonged ICU stay, and more extended hospitalization are at increased risk for PUs; as a result strategies to minimize PU development need further refinement.