Strict adherence to an anticoagulation protocol significantly reduces the prevalence of SCI after catheter ablation of AF with RF energy.

Background: Ischemic stroke has no approved treatments to enhance recovery. ALD-401 is an enriched population of aldehyde dehydrogenase-bright stem cells, capable of reducing neurological deficits in animal models. The primary objective of this trial was to determine the safety of internal carotid artery, intra-arterially delivered autologous bone marrow–derived ALD-401 in patients with disabling middle cerebral artery stroke in comparison with sham harvest with sham infusion. Secondary objectives were to determine feasibility and efficacy. Methods: This was a prospective phase 2, industry-funded, randomized, sham-controlled, parallel-group, multicenter study with blinded assessments. One hundred subjects were planned, aged 30 to 83 years, with confirmed first-time middle cerebral artery ischemic stroke with modified Rankin scale ≥3. Study patients were randomly assigned 3:2 to bone marrow harvest at 11 to 17 days after stroke followed 2 days later by intracarotid infusion of ALD-401 versus sham harvest and then sham infusion in the same timeframe. The primary study outcome was safety based on the incidence of a 4-point National Institutes of Health Stroke Scale worsening and the proportion of serious adverse events. Efficacy was based on modified Rankin scale change at 90 days. Other secondary outcomes were the proportions of patients experiencing adverse events, disability by Barthel Index, quality of life using EQ-5D, rehabilitation utilization, disability at 1 year, and MRI evidence of complications. Results: There were no infusional or allergic reactions and no difference in treatment emergent adverse events. Four patients had small areas of asymptomatic restricted diffusion on MRI in the treatment group. There was no significant difference between the ALD-401 and placebo groups on the modified Rankin scale for the intent-to-treat population at day 90 (mean difference, 0.3; 95% CI, –0.3 to 0.8; P =0.330). There were no significant differences between the groups on any of the secondary efficacy measures. Conclusions: Intracarotid infusion of ALD-401 does not lead to clinical adverse events in patients with subacute ischemic stroke, although there was a higher incidence of small lesions on MRI in the treatment group. There was no difference in the primary efficacy end point between the groups. The study provides a framework for the design and conduct of future intra-arterial cell therapy trials in stroke. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01273337.

During the past decade, there has been an increasing interest in early diagnosis and treatment of traumatic brain injuries (TBI) that lead to chronic traumatic encephalopathy (CTE). The subjects involved range from soldiers exposed to concussive injuries from improvised explosive devices (IEDs) to a significant number of athletes involved in repetitive high force impacts. Although the forces from IEDs are much greater by a magnitude than those from contact sports, the higher frequency associated with contact sports allows for more controlled assessment of the mechanism of action. In our study, we report findings in university-level women soccer athletes followed over a period of four and a half years from accession to graduation. Parameters investigated included T1-, T2-, and susceptibility-weighted magnetic resonance images (SWI), IMPACT (Immediate Post-Concussion Assessment and Cognitive Testing), and C3 Logix behavioral and physiological assessment measures. The MRI Studies show several significant findings: first, a marked increase in the width of sulci in the frontal to occipital cortices; second, an appearance of subtle hemorrhagic changes at the base of the sulci; third was a sustained reduction in total brain volume in several soccer players at a developmental time when brain growth is generally seen. Although all of the athletes successfully completed their college degree and none exhibited long term clinical deficits at the time of graduation, the changes documented by MRI represent a clue to the pathological mechanism following an injury paradigm. The authors propose that our findings and those of prior publications support a mechanism of injury in CTE caused by an autoimmune process associated with the release of neural proteins from nerve cells at the base of the sulcus from a water hammer injury effect. As evidence accumulates to support this hypothesis, there are pharmacological treatment strategies that may be able to mitigate the development of long-term disability from TBI.

The use of rCBV as a response metric in clinical trials has been hampered, in part, due to variations in the biomarker consistency and associated interpretation across sites, stemming from differences in image acquisition and post-processing methods. This study leveraged a dynamic susceptibility contrast magnetic resonance imaging digital reference object to characterize rCBV consistency across 12 sites participating in the Quantitative Imaging Network (QIN), specifically focusing on differences in site-specific imaging protocols (IPs; n = 17), and PMs (n = 19) and differences due to site-specific IPs and PMs (n = 25). Thus, high agreement across sites occurs when 1 managing center processes rCBV despite slight variations in the IP. This result is most likely supported by current initiatives to standardize IPs. However, marked intersite disagreement was observed when site-specific software was applied for rCBV measurements. This study's results have important implications for comparing rCBV values across sites and trials, where variability in PMs could confound the comparison of therapeutic effectiveness and/or any attempts to establish thresholds for categorical response to therapy. To overcome these challenges and ensure the successful use of rCBV as a clinical trial biomarker, we recommend the establishment of qualifying and validating site- and trial-specific criteria for scanners and acquisition methods (eg, using a validated phantom) and the software tools used for dynamic susceptibility contrast magnetic resonance imaging analysis (eg, using a digital reference object where the ground truth is known).