Transforming Research and Clinical Knowledge in Spinal Cord Injury (TRACK-SCI): an overview of initial enrollment and demographics.

OBJECTIVE: Traumatic spinal cord injury (SCI) is a dreaded condition that can lead to paralysis and severe disability. With few treatment options available for patients who have suffered from SCI, it is important to develop prospective databases to standardize data collection in order to develop new therapeutic approaches and guidelines. Here, the authors present an overview of their multicenter, prospective, observational patient registry, Transforming Research and Clinical Knowledge in SCI (TRACK-SCI). METHODS: Data were collected using the National Institute of Neurological Disorders and Stroke (NINDS) common data elements (CDEs). Highly granular clinical information, in addition to standardized imaging, biospecimen, and follow-up data, were included in the registry. Surgical approaches were determined by the surgeon treating each patient; however, they were carefully documented and compared within and across study sites. Follow-up visits were scheduled for 6 and 12 months after injury. RESULTS: One hundred sixty patients were enrolled in the TRACK-SCI study. In this overview, basic clinical, imaging, neurological severity, and follow-up data on these patients are presented. Overall, 78.8% of the patients were determined to be surgical candidates and underwent spinal decompression and/or stabilization. Follow-up rates to date at 6 and 12 months are 45% and 36.3%, respectively. Overall resources required for clinical research coordination are also discussed. CONCLUSIONS: The authors established the feasibility of SCI CDE implementation in a multicenter, prospective observational study. Through the application of standardized SCI CDEs and expansion of future multicenter collaborations, they hope to advance SCI research and improve treatment.

The ED-SED Study: A Multicenter, Prospective Cohort Study of Practice Patterns and Clinical Outcomes Associated With Emergency Department SEDation for Mechanically Ventilated Patients.

OBJECTIVES: To characterize emergency department sedation practices in mechanically ventilated patients, and test the hypothesis that deep sedation in the emergency department is associated with worse outcomes. DESIGN: Multicenter, prospective cohort study. SETTING: The emergency department and ICUs of 15 medical centers. PATIENTS: Mechanically ventilated adult emergency department patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All data involving sedation (medications, monitoring) were recorded. Deep sedation was defined as Richmond Agitation-Sedation Scale of -3 to -5 or Sedation-Agitation Scale of 2 or 1. A total of 324 patients were studied. Emergency department deep sedation was observed in 171 patients (52.8%), and was associated with a higher frequency of deep sedation in the ICU on day 1 (53.8% vs 20.3%; p < 0.001) and day 2 (33.3% vs 16.9%; p = 0.001), when compared to light sedation. Mean (SD) ventilator-free days were 18.1 (10.8) in the emergency department deep sedation group compared to 20.0 (9.8) in the light sedation group (mean difference, 1.9; 95% CI, -0.40 to 4.13). Similar results according to emergency department sedation depth existed for ICU-free days (mean difference, 1.6; 95% CI, -0.54 to 3.83) and hospital-free days (mean difference, 2.3; 95% CI, 0.26-4.32). Mortality was 21.1% in the deep sedation group and 17.0% in the light sedation group (between-group difference, 4.1%; odds ratio, 1.30; 0.74-2.28). The occurrence rate of acute brain dysfunction (delirium and coma) was 68.4% in the deep sedation group and 55.6% in the light sedation group (between-group difference, 12.8%; odds ratio, 1.73; 1.10-2.73). CONCLUSIONS: Early deep sedation in the emergency department is common, carries over into the ICU, and may be associated with worse outcomes. Sedation practice in the emergency department and its association with clinical outcomes is in need of further investigation.

Safety and effectiveness of early chemical deep venous thrombosis prophylaxis after spinal cord injury: pilot prospective data.

OBJECTIVE Spinal cord injuries (SCIs) occur in approximately 17,000 people in the US each year. The average length of hospital stay is 11 days, and deep venous thrombosis (DVT) rates as high as 65% are reported in these patients. There is no consensus on the appropriate timing of chemical DVT prophylaxis for this critically injured patient cohort. The object of this study was to determine if low-molecular-weight heparin (LMWH) was safe and effective if given within 24 hours of SCI. METHODS The Transforming Research and Clinical Knowledge in SCIs study is a prospective observational study conducted by the UCSF Brain and Spinal Injury Center. Protocol at this center includes administration of LMWH within 24 hours of SCI. Data were retrospectively reviewed to determine DVT rate, pulmonary embolism (PE) rate, and hemorrhagic complications. RESULTS Forty-nine patients were enrolled in the study. There were 3 DVTs (6.1%), 2 PEs (4.1%), and no hemorrhagic complications. Regression modeling did not find an association between DVT and/or PE and age, American Spinal Injury Association grade, sex, race, or having undergone a neurosurgical procedure. CONCLUSIONS A standardized protocol in which LMWH is given to patients with SCI within 24 hours of injury is effective in keeping venous thromboembolism at the lower end of the reported range, and is safe, with a zero rate of adverse bleeding events.

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.

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.

Vasopressor support in managing acute spinal cord injury: current knowledge.

INTRODUCTION: Managing neurogenic shock following acute traumatic spinal cord injury (SCI) is challenging. Current guidelines target mean arterial pressure (MAP) above 85-90 mmHg to maintain cord perfusion and reduce ischemia/secondary injury. While early vasopressor utilization has been associated with improved outcomes, recent updates regarding indications of specific vasopressors for refinement of existing guidelines are needed. EVIDENCE ACQUISITION: A comprehensive search was conducted using the National Library of Medicine PubMed database between 01/2010 and 01/2017 targeting vasopressor use in the setting of neurogenic/spinal shock and/or hypotension following acute SCI in adult patients. Special focus was provided for endpoints of comparative advantage, complications, and adjunctive agents. EVIDENCE SYNTHESIS: Seven reports met inclusion criteria. In complete and incomplete SCI, rates of vasopressor-associated complications were greater for dopamine compared to phenylephrine. Norepinephrine provided a comparative 2-mmHg increase to spinal cord perfusion pressure without differential MAP effects versus dopamine. In elderly SCI, more vasopressor and dopamine-specific complications were observed. A case series found adjunct oral pseudoephedrine to be successful in wean off intravenous vasopressors. One study of various MAP thresholds 65-90 mmHg found no correlations with neurological outcome. CONCLUSIONS: Class III evidence has been augmented regarding vasopressor usage following acute SCI, however comparative benefits between vasopressors remain in need of elucidation due to small sample sizes and/or inadequate specificity to spine injury levels. Large prospective multicenter studies targeting age cohorts, and characterizing associated comorbidities and complication profiles, are of high priority in order to determine judicious use criteria of specific vasopressors for relevant subpopulations.

Increased focal hemosiderin deposition in pediatric medulloblastoma patients receiving radiotherapy at a later age.

OBJECT: Focal hemosiderin deposition (FHD) is commonly observed on brain MRI scans of patients treated for childhood medulloblastoma (MB). The authors sought to determine the clinical significance of FHD and its relationship to patient age, radiation dose, and cognitive outcomes. METHODS: A single-institution retrospective study of 93 MB patients at Lucile Packard Children's Hospital at Stanford from 1998 to 2011 identified 41 patients with a negative baseline MRI scan and at least 2 posttreatment MRI scans obtained with T2* gradient recalled echo (GRE). The number and cumulative rate of FHDs detectable by GRE were compared between patients aged 6 years and younger (early age) and aged 7-21 years (late age) at the time of radiotherapy (RT) and between low-dose (1800-2340 cGy) and high-dose (2920-3960 cGy) RT. RESULTS: The median age at MB diagnosis was 7.3 years (range 0.9-21.0 years), the median clinical follow-up period was 5.8 years (range 0.8-13.4 years), and the median 5-year overall survival was 81% ± 7%. Of 30 school-aged children with MB, 21 (70%) required special education, and the median IQ of 10 tested patients was 100 (range 50-118). Thirty-three patients (80%) had FHD after a median latency of 1.9 years (range 0.1-5.9 years). Ninety-four percent (436 of 466) of the lesions arose in the supratentorial region of the brain, whereas 29 (6%) resided in the brainstem or the cerebellum. No spinal lesions were observed on routine spine MRI scans using T2 fast spin echo imaging. The mean cumulative lesion rate per year was 2.23 ± 3.05, and this rate was higher in older children at the time of RT compared with younger children (3.23 vs 0.67 per year, p = 0.002) but did not differ among different RT doses (p = 0.395). A child's IQ or need for special education showed no significant correlation with the rate of lesion development or number of lesions. None of the lesions resulted in symptomatic hemorrhage that required surgical intervention. CONCLUSIONS: More FHD was observed in children treated for MB at the older ages than in those treated at the younger ages. There was no significant association of the incidence of FHD with radiation dose or cognitive outcomes, and none of the lesions required surgical intervention.