The neurocognitive effects of a conducted electrical weapon compared to high intensity interval training and alcohol intoxication - implications for Miranda and consent.

While the physiologic effects of conducted electrical weapons (CEW) have been the subjects of numerous studies over nearly two decades, their effects on neurocognitive functioning, both short-term and long-term, have only recently been studied. In a 2014 study involving use-of-force scenarios, including a CEW scenario, we found that there was a decline in neurocognitive performance immediately post-scenario in all groups; however this effect was transient, of questionable clinical/legal significance, not statistically different between the groups, and, returned to baseline by one hour post-scenario. Two subsequent studies by other authors have also found transient neurocognitive effects in the immediate post-exposure period; however, in one study, the effect was greater in one measure (of 5) for the CEW compared to exertion, and the authors suggested that this effect could have implications for the Miranda waiver obtained before custodial interrogation as well as consent. In our current study, we compared the neurocognitive effects of an exposure to a CEW to another exertion regimen, as well as to alcohol intoxication given the latter has significant established case law with regard to the Miranda waiver and consent. Such a comparison may offer more insight into the clinical/legal significance of any measured changes. As with the prior studies, the neurocognitive performance decrements of the CEW and exertion regimens, found only in one measure in this study (of three), were transient, and here, non-significant. Only alcohol intoxication resulted in statistically significant performance declines across all measures and these were persistent over the study period. Given that the neurocognitive changes associated with the CEW were non-significant, but were significant for alcohol intoxication, and given that current case law does not use intoxication as a per se or bright line barrier to Miranda and consent, our results do not suggest that a CEW exposure should preclude waiving of Miranda rights or obtaining consent.

Predictors of mortality in veterans with traumatic spinal cord injury.

STUDY DESIGN: Retrospective. OBJECTIVES: To determine the predictors of mortality in veterans with traumatic spinal cord injury (tSCI). SETTING: Tertiary clinic in the state of Oklahoma. METHODS: One hundred and forty-seven patients with tSCI who were enrolled in our Spinal Cord Injury program from 1 January 2000 to 31 December 2011 were retrospectively studied. The study sample was divided into two groups, based on the survival status by 31 December 2011. RESULTS: In this sample of 147 patients with tSCI, survival at the end of the 12-year study period was 60%. There were three major causes of death: infection-related, such as pneumonia (21%), urinary infection (14%), and infection of the pressure ulcers (11%); cardiovascular-related, such as congestive heart failure (16%), coronary arterial disease (13%), and atrial fibrillation (2%); and cancer-related (16%). In veterans with complete SCI, deaths were mainly infection-related and occurred in the hospital (51%), while deaths in veterans with incomplete SCI were primarily cardiovascular and cancer-related and occurred in the community. A Cox regression analysis showed the age at the time of injury to be the main predictor of SCI-related mortality. CONCLUSION: This study suggests that an older age at the time of injury is a significant predictor of mortality following tSCI with patients more likely to die from cardiovascular deaths than the general population. These findings support the need for preventative strategies, including a focus on cardiovascular risk factor management, in order to decrease long-term mortality.

Coated-platelet levels and progression from mild cognitive impairment to Alzheimer disease.

OBJECTIVES: Coated-platelets are a subset of platelets produced by dual-agonist activation with collagen and thrombin. These platelets retain full-length amyloid precursor protein on their surface, are elevated in patients with amnestic as compared to nonamnestic mild cognitive impairment (MCI), and correlate with disease progression in Alzheimer disease (AD). Prompted by these findings, we investigated the association between coated-platelet production in amnestic MCI and rate of progression to AD. METHODS: Coated-platelet levels were assayed in 74 patients with amnestic MCI who were subsequently followed longitudinally for up to 36 months in an outpatient dementia clinic. Levels are reported as percent of cells converted into coated-platelets. Subjects were categorized into tertiles of coated-platelet levels. The distributions of time to progression to AD were estimated for each tertile using cumulative incidence curves and compared statistically using a log-rank test. Cox proportional hazards regression was used to adjust for potential confounders. RESULTS: The 24-month cumulative incidence of progression to AD was different among tertiles: 4% for the first tertile (lowest coated-platelet levels), 13% for the second tertile, and 37% for the third tertile (overall log-rank test, p = 0.02). The hazard rate of progression to AD for patients in the highest coated-platelet tertile was 5.1 times that for patients in the lowest tertile (p = 0.04), whereas the hazard rate for the middle tertile was similar to that for the lowest tertile (hazard rate ratio = 1.5, p = 0.7). CONCLUSIONS: Elevated coated-platelet levels in patients with amnestic MCI are associated with increased risk for progression to AD.

The role of stem cell factor and c-KIT in keloid pathogenesis: do tyrosine kinase inhibitors have a potential therapeutic role?

BACKGROUND: Keloids are fibroproliferative disorders characterized by increased deposition of extracellular matrix components. Stem cell factor (SCF) and its receptor c-KIT are expressed in a wide variety of cells and have also been demonstrated to be important modulators of the wound healing process. OBJECTIVES: To examine the role of the SCF/c-KIT system in keloid pathogenesis. METHODS: Immunohistochemical staining and Western blot analyses were used to examine localization and expression of SCF and c-KIT in keloid and normal skin tissue. This was followed by the detection of SCF and c-KIT expression in fibroblasts cultured in vitro and fibroblasts exposed to serum. To investigate the effect of epithelial-mesenchymal interactions, a two-chamber system was employed in which keratinocytes on membrane inserts were cocultured with the fibroblasts. SCF and c-KIT expression levels in all cell extracts and conditioned media were assayed by Western blotting. In another set of experiments, the effect of imatinib (Glivec(®), Gleevec(®); Novartis Pharma AG, Basel, Switzerland) on keloid fibroblasts was examined. RESULTS: SCF and c-KIT were upregulated in keloid scar tissue and in cultured fibroblasts stimulated with serum, highlighting their importance in the initial phase of wound healing. We further demonstrated that epithelial-mesenchymal interactions, mimicked by coculture of keratinocytes and fibroblasts in vitro, not only stimulated secretion of the soluble form of SCF in keloid cocultures but also brought about shedding of the extracellular domain of c-KIT perhaps by upregulation of tumour necrosis factor-α converting enzyme which was also upregulated in keloid scars in vivo and keloid cocultures in vitro. In addition keloid cocultures expressed increased levels of phosphorylated c-KIT highlighting an activation of the SCF/c-KIT system. Finally, we demonstrated that imatinib, a tyrosine kinase inhibitor, may be a possible therapeutic agent for keloids. CONCLUSION: These data indicate that the SCF/c-KIT system plays an important role in scar pathogenesis, and underscore the role of imatinib as a key therapeutic agent in keloid scars.

Coated-platelets in ischemic stroke: differences between lacunar and cortical stroke.

BACKGROUND: Coated-platelets are a subset of platelets with procoagulant potential observed upon dual agonist stimulation with collagen and thrombin. OBJECTIVE: The goal was to investigate if coated-platelet production differs between patients with lacunar ischemic stroke and non-lacunar (cortical) ischemic stroke as compared with controls. PATIENTS AND METHODS: Blood samples from 60 patients with ischemic stroke (20 lacunar and 40 cortical) and 70 controls were analyzed for coated-platelet production. RESULTS: Coated-platelet production was significantly lower in patients with lacunar stroke (21.8 +/- 11.4%, mean +/- 1 SD) as compared with either controls (31.6 +/- 13.2%, P = 0.008) or patients with cortical stroke (39.4 +/- 12.7%, P < 0.001). The increase in coated-platelets for patients with cortical stroke as compared with controls was also significant (P = 0.008). CONCLUSIONS: Our results indicate a marked difference in coated-platelet synthesis in lacunar vs. non-lacunar stroke, thereby providing additional support for the existence of distinct pathological processes underlying these two subtypes of ischemic stroke. Further investigation of the role of coated-platelets in stroke, taking into account these preliminary findings, is warranted.