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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Immune depression after trauma-hemorrhage has been implicated as an important factor in the pathogenesis of sepsis and septic-organ failure. Although recent studies have implicated immune-cell apoptosis as an important factor in the evolution of this posttrauma immune-suppressed state, neither the initial triggers that induce this response nor the cellular pathways through which these triggering pathways act have been fully defined. Thus, the current study tests the hypothesis that acute splenic and thymic immune-cell apoptosis developing after trauma-hemorrhagic shock (T/HS) is due to gut-derived factors carried in intestinal lymph and that this T/HS lymph-induced immune depressed state is mediated through Toll-like receptor 4 (TLR4). ⋯ However, the TLR4mut mice were resistant to T/HS lymph-induced splenic apoptosis. Furthermore, the WT, but not the TLR4mut mice developed splenic apoptosis after actual T/HS. In conclusion, gut-derived factors appear to initiate a sequence of events that leads to an acute increase in splenic and thymic immune-cell apoptosis, and this process is TLR4-dependent.
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Circulating microRNAs (miRNAs) are an emerging biomarker for sepsis patients. The purpose of this study was to identify novel miRNAs in the sera of sepsis patients and determine their prognostic value. Ninety-four serum samples were collected from sepsis patients within 24 h of intensive care unit admission. ⋯ Conjoint analysis of the six miRNAs and severity scores (Acute Physiology and Chronic Health Evaluation II score and Sequential Organ Failure Assessment score) showed that the area under the receiver operating characteristic curve for the predictive value of the six miRNAs was 0.969 (95% confidence interval, 0.930-1.000). When the cutoff point was set at 0.714, the six miRNAs and severity score provided a sensitivity of 100% and a specificity of 82.6%. In conclusion, 41 novel miRNAs were detectable in the sera of sepsis patients, and six of them might be related to sepsis outcome.
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With animal models, death as an intentional end point is ethically unacceptable. However, in the study of septic shock, death is still considered the only relevant end point. We defined eight humane end points into four stages of severity (from healthy to moribund) and used to design a clinically relevant scoring tool, termed "the mouse clinical assessment score for sepsis" (M-CASS). ⋯ The M-CASS displayed a high internal consistency (Cronbach α = 0.97) with a high level of agreement and an intraclass correlation coefficient equal to 0.91. The plasma levels of cytokines and markers of oxidative stress were all associated with the M-CASS score (Kruskal-Wallis test, P < 0.05). The M-CASS allows tracking of disease progression and animal welfare requirements.