Journal of neurotrauma
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Journal of neurotrauma · Sep 2023
Randomized Controlled TrialThe RISCIS-PK substudy: An analysis of pharmacokinetics, pharmacodynamics, and impact on axonal degradation of riluzole in patients with traumatic cervical spinal cord injury enrolled in the RISCIS Phase III Randomized Controlled Trial.
To date, no drug therapy has shown significant efficacy in improving functional outcomes in patients with acute spinal cord injury (SCI). Riluzole is an approved benzothiazole sodium channel blocker to attenuate neurodegeneration in amyotrophic lateral sclerosis (ALS) and is of interest for neuroprotection in SCI. In a Phase I clinical trial (ClinicalTrials.gov Identifier: NCT00876889), riluzole was well tolerated with a 2-week treatment at the dose level approved for ALS and exhibited potential efficacy in patients with SCI. ⋯ The development of effective treatment for SCI is challenging. However, the future model-informed and PK-guided drug development and regimen modification can be rationally executed with the optimal dosing regimen design based on the developed 3D PK/PD model. The PK/PD/CO model can serve as a rational guide for future drug development, PKPD model refinement, and extension to other studies in SCI settings.
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Journal of neurotrauma · Sep 2023
Demographics, Mechanism of Injury and Outcomes for Acute Upper and Lower Cervical Spinal Cord Injuries - An Analysis of 470 Patients in the Prospective, Multicenter North American Clinical Trials Network (NACTN) Registry.
There is a paucity of data comparing the demographics, mechanism of injury, and outcomes of upper versus lower cervical spinal cord injuries (cSCI). The study objective was to define different clinical manifestations of cSCI. Data were collected prospectively through centers of the North American Clinical Trials Network (NACTN). ⋯ In conclusion, there appears to be a natural demarcation of injury type between C3 and C4. Upper cSCI (C1-C3) was more associated with falls and diabetes, whereas lower cSCI (C4-C7) was more associated with sports, worse ASIA scores, and more complications. Further research will be needed to understand the mechanistic and biological differences between these two groups and whether different treatments may be appropriate for each of these groups.
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Journal of neurotrauma · Sep 2023
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. ⋯ 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.
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Journal of neurotrauma · Sep 2023
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. ⋯ 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.
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Traumatic spinal cord injury (SCI) causes a sudden onset multi-system disease, permanently altering homeostasis with multiple complications. Consequences include aberrant neuronal circuits, multiple organ system dysfunctions, and chronic phenotypes such as neuropathic pain and metabolic syndrome. Reductionist approaches are used to classify SCI patients based on residual neurological function. ⋯ To better understand the evolution from acute SCI to chronic SCI multi-system states, we propose a topological phenotype framework integrating bioinformatics, physiological data, and allostatic load tested against accepted established recovery metrics. This form of correlational phenotyping may reveal critical nodal points for intervention to improve recovery trajectories. This study examines the limitations of current classifications of SCI and how these can evolve through systems medicine.