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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Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related mortality and morbidity. Combination of TBI and HS (TBI + HS) is highly lethal, and the optimal resuscitation strategy for this combined insult remains unclear. A critical limitation is the lack of suitable large animal models to test different treatment strategies. ⋯ Hex treatment decreased the swelling (29% ± 1.6%) without reducing the lesion size. Early administration of FFP reduces the size of brain lesion and associated swelling in a large animal model of TBI + HS. In contrast, artificial colloid (Hex) decreases swelling without reducing the actual size of the brain lesion.
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Randomized Controlled Trial Multicenter Study
Normal-range blood lactate concentration in septic shock is prognostic and predictive.
We hypothesized that lactate levels even within the normal range are prognostic and that low lactate levels predict a beneficial response to vasopressin infusion in septic shock. We conducted a retrospective analysis using the Vasopressin in Septic Shock Trial (VASST) as a derivation cohort (n = 665), then validated using another single-center septic shock cohort, St Paul's Hospital (SPH) cohort (n = 469). Lactate levels were divided into quartiles. ⋯ Lactate concentrations of 1.4 mmol/L or less predicted a beneficial response in those randomized to vasopressin compared with noradrenaline in VASST (P < 0.05). Lactate concentrations within the "normal" range can be a useful prognostic indicator in septic shock. Furthermore, patients whose lactate level is less than or equal to 1.4 mmol/L may benefit from vasopressin infusion.
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Comparative Study
A comparison of the time from sepsis to inception of continuous renal replacement therapy versus RIFLE criteria in patients with septic acute kidney injury.
We hypothesized that the time from sepsis to inception of continuous renal replacement therapy (CRRT) can be used to predict survival rates in patients with septic acute kidney injury (AKI). The survival predictability of CRRT inception time was compared with that of RIFLE criteria, which were previously used in clinical practice. We retrospectively analyzed outcomes in 55 patients with septic AKI admitted to the medical intensive care unit at Asan Medical Center (Seoul, Korea) between April 2009 and October 2010. ⋯ Ventilator-free day at day 28 was longer in the early group than that in the late group (7.5 vs. 0 d; P = 0.033). After adjustment for covariates, we found that the late group (hazard ratio, 3.106; 95% confidence interval, 1.066-9.047) and Sequential Organ Failure Assessment at sepsis (hazard ratio, 1.410; 95% confidence interval, 1.108-1.796) were independent factors associated with 28-day mortality. This study suggests that the time interval from sepsis to CRRT inception may be a more useful predictor of 28-day mortality than RIFLE criteria in patients with septic AKI.
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Glucocorticoids remain a recommended therapy in advanced septic shock despite the often unpredictable response, and our understanding of the mechanisms regulating the steroid and stress response remains limited. Since the initial sequencing of the human glucocorticoid receptor α and β gene (hGRα and hGRβ), only three additional splice variants have been identified--all of which have been postulated to contribute to steroid resistance. During a survey of 97 healthy humans' blood, we identified two novel hGR splice isoforms (hGR-S1 and hGR-S1(-349A) retaining intron H between exons 8 and 9. ⋯ Removal of the 3' untranslated region (3'UTR) of the hGR-S1(-349A) mRNA sequence resulted in a loss of the augmented response. The isoform hGR-S1(-349A) augments the response to steroids, and this significant response appears to be critically regulated by the 3'UTR. The identification and evaluation of these unique hGR isoforms helps further the understanding of the complex genetic regulation of the stress and steroid response.
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Sex influences the severity and evolution of various inflammatory conditions. Although many studies have demonstrated the role of sex hormones in immune response modulation, recent clinical data revealed significant sex differences in inflammatory markers in prepubertal children, suggesting a genetic contribution. We studied several immune functions depending on X-linked genes in healthy adults of both sexes: the respiratory burst of purified neutrophils, the CD99 and CD11b expression of stimulated leukocytes as markers of adhesion and diapedesis, and the production of inflammatory cytokines in whole blood after incubation with lipopolysaccharide for 24 h. ⋯ Tumor necrosis factor α production significantly correlated with monocyte count, with men having a higher monocyte count than women. When cytokine levels were normalized to monocyte counts, a higher IL-8 production was found in women, which may explain the higher neutrophil count observed in girls with acute inflammatory diseases, because IL-8 is a major neutrophil chemoattractant. These sex differences regarding the activation of certain X-linked genes involved in innate immunity confirm our clinical observations, thus supporting the role of sex chromosomes in inflammatory response.