Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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We evaluated the potential utility of a new prototype noninvasive muscle oxygenation (MOx) measurement for the identification of shock severity in a population of patients admitted to the trauma resuscitation rooms of a Level I regional trauma center. The goal of this project was to correlate MOx with shock severity as defined by standard measures of shock: systolic blood pressure, heart rate, and lactate. ⋯ The results obtained from this pilot study indicate that MOx correlates with shock severity in a population of trauma patients. Noninvasive and continuous MOx holds promise to aid in patient triage and to evaluate patient condition throughout the course of resuscitation.
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Erythrocyte-derived microparticles (MPs) are sub-micrometer, biologically active vesicles shed by red blood cells as part of the biochemical changes that occur during storage. We hypothesized that MPs from stored red blood cells would activate endothelial cells. MPs from aged murine packed red blood cells (pRBCs) were isolated and used to treat confluent layers of cultured endothelial cells. ⋯ IL-6 in cell culture supernatants was increased after 12 h of MP stimulation compared with controls (1.24 vs. 0.73 ng/mL, P = 0.03). In vivo experiments demonstrated that MP injection increased ELAM-1 and ICAM-1 expression at 1 h (18.56 vs. 7.08 RFI, P < 0.01, and 23.66 vs. 6.87 RFI, P < 0.01, respectively) and caused increased density of pulmonary interstitial leukocytes by 4 h of treatment (69.25 vs. 29.25 cells/high powered field, P < 0.01). This series of experiments supports our hypothesis that erythrocyte-derived MPs are able to activate pulmonary endothelium, leading to the pulmonary sequestration of leukocytes following the transfusion of stored pRBCs.
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To effectively improve outcomes of septic patients, we first need to elucidate the multifaceted pathogenesis of sepsis syndromes and related inflammatory conditions. In fulfillment of such needs, in February 2016, new definitions for sepsis and septic shock were published under the acronym Sepsis-3. Although aimed at the clinical area, Sepsis-3 will have an inevitable influence upon the field of translational research as well. ⋯ This could be achieved, for example, by generating consensus guidelines that would support scientists in their study design and optimal sepsis modeling decision-making. An implementation of such hypothetical "Minimum Quality Threshold in Preclinical Sepsis Studies" guidelines across different species has a strong potential for making sepsis studies more reliable and transpolatable. We strongly believe that an internationally coordinated standardization effort in sepsis modeling will certainly serve the above purposes well.
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The neonatal innate immune system differs to microbial infection both quantitatively and qualitatively when compared with adults. Here, we provide the first genome-wide ex-vivo expression profile of umbilical cord blood (UCB) neutrophils from full-term infants prior to and in response to whole-blood lipopolysaccharide (LPS) stimulation. Additionally, we provide cytokine expression prior to and following LPS stimulation. The genomic expression and cytokine profile are compared with LPS-stimulated whole blood from healthy adult subjects (HC). ⋯ LPS-stimulated whole blood from UCB exhibited a markedly suppressed inflammatory cytokine production and PMN innate immune genome response. These differences in gene expression and cytokine production may be an adaptive response to a prior fetal environment, but may also explain their increased susceptibility to infections. Characterization of these deficits is the first step toward developing prophylactic and therapeutic interventions.