Traumatic pedestrian and bicyclist injuries associated with intoxication.

BACKGROUND: Drug and alcohol use are risk factors for trauma among operators of motor vehicles and contribute to trauma in pedestrians and bicyclists. We describe the prevalence of drug and alcohol use and clinical consequences in a cohort of pedestrians and bicyclists with trauma. METHODS: We analyzed a 25-month data set of 916 trauma team activations from January 2017-January 2019 at an urban, level I trauma center. Blood ethanol levels and urine toxicology screens were obtained in 94 pedestrian and bicyclist trauma activations. We compared pedestrians or bicyclists with a positive urine or blood screen (n = 69) to those with negative screens (n = 25). We conducted a retrospective chart review to determine mechanism of injury, injury pattern, and disposition from the emergency department (ED). RESULTS: Overall, 38 (55%) of injured patients with positive screen were pedestrians and 31 (45%) were bicyclists. Fentanyl was the most commonly detected drug (n = 38; 40%), followed by opiates (n = 27; 29%), and tetrahydrocannabiol (THC) (n = 23; 25%). Twenty-one patients were positive for ethanol. Pedestrians and bicyclists with positive toxicology screens were significantly more likely to sustain fractures (p < .01), require an operative procedure (p < .05), or intensive care unit admission (p < .05). CONCLUSION: Our study builds on previous literature which suggests that intoxicated bicyclists and pedestrians suffer frequent and more severe injury than their sober counterparts. Public health campaigns should educate bicyclists and pedestrians about the risks of cycling or walking in areas of road traffic while under the influence of alcohol or illicit drugs.

Age-Dependent Metabolic and Immunosuppressive Effects of Tacrolimus.

Immunosuppression in elderly recipients has been underappreciated in clinical trials. Here, we assessed age-specific effects of the calcineurin inhibitor tacrolimus (TAC) in a murine transplant model and assessed its clinical relevance on human T cells. Old recipient mice exhibited prolonged skin graft survival compared with young animals after TAC administration. More important, half of the TAC dose was sufficient in old mice to achieve comparable systemic trough levels. TAC administration was able to reduce proinflammatory interferon-γ cytokine production and promote interleukin-10 production in old CD4+ T cells. In addition, TAC administration decreased interleukin-2 secretion in old CD4+ T cells more effectively while inhibiting the proliferation of CD4+ T cells in old mice. Both TAC-treated murine and human CD4+ T cells demonstrated an age-specific suppression of intracellular calcineurin levels and Ca2+ influx, two critical pathways in T cell activation. Of note, depletion of CD8+ T cells did not alter allograft survival outcome in old TAC-treated mice, suggesting that TAC age-specific effects were mainly CD4+ T cell mediated. Collectively, our study demonstrates age-specific immunosuppressive capacities of TAC that are CD4+ T cell mediated. The suppression of calcineurin levels and Ca2+ influx in both old murine and human T cells emphasizes the clinical relevance of age-specific effects when using TAC.