A phase I/IIa clinical trial of a recombinant Rho protein antagonist in acute spinal cord injury.

Multiple lines of evidence have validated the Rho pathway as important in controlling the neuronal response to growth inhibitory proteins after central nervous system (CNS) injury. A drug called BA-210 (trademarked as Cethrin(®)) blocks activation of Rho and has shown promise in pre-clinical animal studies in being used to treat spinal cord injury (SCI). This is a report of a Phase I/IIa clinical study designed to test the safety and tolerability of the drug, and the neurological status of patients following the administration of a single dose of BA-210 applied during surgery following acute SCI. Patients with thoracic (T2-T12) or cervical (C4-T1) SCI were sequentially recruited for this dose-ranging (0.3 mg to 9 mg Cethrin), multi-center study of 48 patients with complete American Spinal Injury Association assessment (ASIA) A. Vital signs; clinical laboratory tests; computed tomography (CT) scans of the spine, head, and abdomen; magnetic resonance imaging (MRI) of the spine, and ASIA assessment were performed in the pre-study period and in follow-up periods out to 1 year after treatment. The treatment-emergent adverse events that were reported were typical for a population of acute SCI patients, and no serious adverse events were attributed to the drug. The pharmacokinetic analysis showed low levels of systemic exposure to the drug, and there was high inter-patient variability. Changes in ASIA motor scores from baseline were low across all dose groups in thoracic patients (1.8±5.1) and larger in cervical patients (18.6±19.3). The largest change in motor score was observed in the cervical patients treated with 3 mg of Cethrin in whom a 27.3±13.3 point improvement in ASIA motor score at 12 months was observed. Approximately 6% of thoracic patients converted from ASIA A to ASIA C or D compared to 31% of cervical patients and 66% for the 3-mg cervical cohort. Although the patient numbers are small, the observed motor recovery in this open-label trial suggests that BA-210 may increase neurological recovery after complete SCI. Further clinical trials with Cethrin in SCI patients are planned, to establish evidence of efficacy

Association of Pneumonia, Wound Infection, and Sepsis with Clinical Outcomes after Acute Traumatic Spinal Cord Injury.

Pneumonia, wound infections, and sepsis (PWS) are the leading causes of acute mortality after traumatic spinal cord injury (SCI). However, the impact of PWS on neurological and functional outcomes is largely unknown. The present study analyzed participants from the prospective North American Clinical Trials Network (NACTN) registry and the Surgical Timing in Acute SCI Study (STASCIS) for the association between PWS and functional outcome (assessed as Spinal Cord Independence Measure subscores for respiration and indoor ambulation) at 6 months post-injury. Neurological outcome was analyzed as a secondary end-point. Among 1299 participants studied, 180 (14%) developed PWS during the acute admission. Compared with those without PWS, participants with PWS were mostly male (76% vs. 86%; p = 0.007), or presented with mostly American Spinal Injury Association Impairment Scale (AIS) grade A injury (36% vs. 61%; p < 0.001). There were no statistical differences between participants with or without PWS with respect to time from injury to surgery, and administration of steroids. Dominance analysis showed injury level, baseline AIS grade, and subject pre-morbid medical status collectively accounted for 77.7% of the predicted variance of PWS. Regression analysis indicated subjects with PWS demonstrated higher odds for respiratory (odds ratio [OR] 3.91, 95% confidence interval [CI]: 1.42-10.79) and ambulatory (OR 3.94, 95% CI: 1.50-10.38) support at 6 month follow-up in adjusted analysis. This study has shown an association between PWS occurring during acute admission and poorer functional outcomes following SCI

Association of Pneumonia, Wound Infection, and Sepsis with Clinical Outcomes after Acute Traumatic Spinal Cord Injury

Pneumonia, wound infections, and sepsis (PWS) are the leading causes of acute mortality after traumatic spinal cord injury (SCI). However, the impact of PWS on neurological and functional outcomes is largely unknown. The present study analyzed participants from the prospective North American Clinical Trials Network (NACTN) registry and the Surgical Timing in Acute SCI Study (STASCIS) for the association between PWS and functional outcome (assessed as Spinal Cord Independence Measure subscores for respiration and indoor ambulation) at 6 months post-injury. Neurological outcome was analyzed as a secondary end-point. Among 1299 participants studied, 180 (14%) developed PWS during the acute admission. Compared with those without PWS, participants with PWS were mostly male (76% vs. 86%; p  = 0.007), or presented with mostly American Spinal Injury Association Impairment Scale (AIS) grade A injury (36% vs. 61%; p  < 0.001). There were no statistical differences between participants with or without PWS with respect to time from injury to surgery, and administration of steroids. Dominance analysis showed injury level, baseline AIS grade, and subject pre-morbid medical status collectively accounted for 77.7% of the predicted variance of PWS. Regression analysis indicated subjects with PWS demonstrated higher odds for respiratory (odds ratio [OR] 3.91, 95% confidence interval [CI]: 1.42-10.79) and ambulatory (OR 3.94, 95% CI: 1.50-10.38) support at 6 month follow-up in adjusted analysis. This study has shown an association between PWS occurring during acute admission and poorer functional outcomes following SCI

Acute Adverse Events After Spinal Cord Injury and Their Relationship to Long-term Neurologic and Functional Outcomes: Analysis From the North American Clinical Trials Network for Spinal Cord Injury

There are few contemporary, prospective multicenter series on the spectrum of acute adverse events and their relationship to long-term outcomes after traumatic spinal cord injury. The goal of this study is to assess the prevalence of adverse events after traumatic spinal cord injury and to evaluate the effects on long-term clinical outcome. Multicenter prospective registry. Consortium of 11 university-affiliated medical centers in the North American Clinical Trials Network. Eight-hundred one spinal cord injury patients enrolled by participating centers. Appropriate spinal cord injury treatment at individual centers. A total of 2,303 adverse events were recorded for 502 patients (63%). Penalized maximum logistic regression models were fitted to estimate the likelihood of neurologic recovery (ASIA Impairment Scale improvement ≥ 1 grade point) and functional outcomes in subjects who developed adverse events at 6 months postinjury. After accounting for potential confounders, the group that developed adverse events showed less neurologic recovery (odds ratio, 0.55; 95% CI, 0.32-0.96) and was more likely to require assisted breathing (odds ratio, 6.55; 95% CI, 1.17-36.67); dependent ambulation (odds ratio, 7.38; 95% CI, 4.35-13.06) and have impaired bladder (odds ratio, 9.63; 95% CI, 5.19-17.87) or bowel function (odds ratio, 7.86; 95% CI, 4.31-14.32) measured using the Spinal Cord Independence Measure subscores. Results from this contemporary series demonstrate that acute adverse events are common and are associated with worsened long-term outcomes after traumatic spinal cord injury

Does MIS Surgery Allow for Shorter Constructs in the Surgical Treatment of Adult Spinal Deformity?

BackgroundThe length of construct can potentially influence perioperative risks in adult spinal deformity (ASD) surgery. A head-to-head comparison between open and minimally invasive surgery (MIS) techniques for treatment of ASD has yet to be performed.ObjectiveTo examine the impact of MIS approaches on construct length and clinical outcomes in comparison to traditional open approaches when treating similar ASD profiles.MethodsTwo multicenter databases for ASD, 1 involving MIS procedures and the other open procedures, were propensity matched for clinical and radiographic parameters in this observational study. Inclusion criteria were ASD and minimum 2-year follow-up. Independent t -test and chi-square test were used to evaluate and compare outcomes.ResultsA total of 1215 patients were identified, with 84 patients matched in each group. Statistical significance was found for mean levels fused (4.8 for circumferential MIS [cMIS] and 10.1 for open), mean interbody fusion levels (3.6 cMIS and 2.4 open), blood loss (estimated blood loss 488 mL cMIS and 1762 mL open), and hospital length of stay (6.7 days cMIS and 9.7 days open). There was no significant difference in preoperative radiographic parameters or postoperative clinical outcomes (Owestry Disability Index and visual analog scale) between groups. There was a significant difference in postoperative lumbar lordosis (43.3° cMIS and 49.8° open) and pelvic incidence-lumbar lordosis correction (10.6° cMIS and 5.2° open) in the open group. There was no significant difference in reoperation rate between the 2 groups.ConclusionMIS techniques for ASD may reduce construct length, reoperation rates, blood loss, and length of stay without affecting clinical and radiographic outcomes when compared to a similar group of patients treated with open techniques

Does MIS Surgery Allow for Shorter Constructs in the Surgical Treatment of Adult Spinal Deformity?

Abstract BACKGROUND: The length of construct can potentially influence perioperative risks in adult spinal deformity (ASD) surgery. A head-to-head comparison between open and minimally invasive surgery (MIS) techniques for treatment of ASD has yet to be performed. OBJECTIVE: To examine the impact of MIS approaches on construct length and clinical outcomes in comparison to traditional open approaches when treating similar ASD profiles. METHODS: Two multicenter databases for ASD, 1 involving MIS procedures and the other open procedures, were propensity matched for clinical and radiographic parameters in this observational study. Inclusion criteria were ASD and minimum 2-year follow-up. Independent t-test and chi-square test were used to evaluate and compare outcomes. RESULTS: A total of 1215 patients were identified, with 84 patients matched in each group. Statistical significance was found for mean levels fused (4.8 for circumferential MIS [cMIS] and 10.1 for open), mean interbody fusion levels (3.6 cMIS and 2.4 open), blood loss (estimated blood loss 488 mL cMIS and 1762 mL open), and hospital length of stay (6.7 days cMIS and 9.7 days open). There was no significant difference in preoperative radiographic parameters or postoperative clinical outcomes (Owestry Disability Index and visual analog scale) between groups. There was a significant difference in postoperative lumbar lordosis (43.3° cMIS and 49.8° open) and pelvic incidence-lumbar lordosis correction (10.6° cMIS and 5.2° open) in the open group. There was no significant difference in reoperation rate between the 2 groups. CONCLUSION: MIS techniques for ASD may reduce construct length, reoperation rates, blood loss, and length of stay without affecting clinical and radiographic outcomes when compared to a similar group of patients treated with open techniques

Acute Adverse Events After Spinal Cord Injury and Their Relationship to Long-term Neurologic and Functional Outcomes: Analysis From the North American Clinical Trials Network for Spinal Cord Injury.

ObjectivesThere are few contemporary, prospective multicenter series on the spectrum of acute adverse events and their relationship to long-term outcomes after traumatic spinal cord injury. The goal of this study is to assess the prevalence of adverse events after traumatic spinal cord injury and to evaluate the effects on long-term clinical outcome.DesignMulticenter prospective registry.SettingConsortium of 11 university-affiliated medical centers in the North American Clinical Trials Network.PatientsEight-hundred one spinal cord injury patients enrolled by participating centers.InterventionsAppropriate spinal cord injury treatment at individual centers.Measurements and main resultsA total of 2,303 adverse events were recorded for 502 patients (63%). Penalized maximum logistic regression models were fitted to estimate the likelihood of neurologic recovery (ASIA Impairment Scale improvement ≥ 1 grade point) and functional outcomes in subjects who developed adverse events at 6 months postinjury. After accounting for potential confounders, the group that developed adverse events showed less neurologic recovery (odds ratio, 0.55; 95% CI, 0.32-0.96) and was more likely to require assisted breathing (odds ratio, 6.55; 95% CI, 1.17-36.67); dependent ambulation (odds ratio, 7.38; 95% CI, 4.35-13.06) and have impaired bladder (odds ratio, 9.63; 95% CI, 5.19-17.87) or bowel function (odds ratio, 7.86; 95% CI, 4.31-14.32) measured using the Spinal Cord Independence Measure subscores.ConclusionsResults from this contemporary series demonstrate that acute adverse events are common and are associated with worsened long-term outcomes after traumatic spinal cord injury