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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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.
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We aimed to evaluate the impact of metformin use on lactate kinetics in patients with severe sepsis and septic shock. ⋯ Lactate levels in metformin users were initially elevated in the early phase of resuscitation from severe sepsis and septic shock. However, there was no significant difference in lactate levels, LC, and normalization over the initial 24 h period based on metformin use.
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Review Meta Analysis
Does Respiratory Variation in Inferior Vena Cava Diameter Predict Fluid Responsiveness: A Systematic Review and Meta-Analysis.
The aim of fluid resuscitation is to increase stroke volume, yet this effect is observed in only 50% of patients. Prediction of fluid responsiveness may allow fluid resuscitation to be administered to those most likely to benefit. The aim of this study was to systematically review the test characteristics of respiratory variation in inferior vena cava (IVC) diameter as a predictor of fluid responsiveness in patients with acute circulatory failure. ⋯ Respiratory variation in IVC diameter has limited ability to predict fluid responsiveness, particularly in spontaneously ventilating patients. A negative test cannot be used to rule out fluid responsiveness. Clinical context should be taken into account when using IVC ultrasound to help make treatment decisions.
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Choosing the appropriate endpoint for a trauma hemorrhage control trial can determine the likelihood of its success. Recent Phase 3 trials and observational studies have used 24-h and/or 30-day all-cause mortality as the primary endpoint and some have not used exception from informed consent (EFIC), resulting in multiple failed trials. Five recent high-quality prospective studies among 4,064 hemorrhaging trauma patients provide new evidence to support earlier primary endpoints. ⋯ Primary endpoints should be congruent with the timing of the disease process. Therefore, if a resuscitation/hemorrhage control intervention is under study, a primary endpoint of all-cause mortality evaluated within the first 6 h is appropriate. Before choosing the timing of the primary endpoint for a large multicenter trial, we recommend performing a Phase 2 trial under EFIC to better understand the effects of the hemorrhage control intervention and distribution of time to death. When early primary endpoints are used, patients should be monitored for multiple subsequent secondary safety endpoints, including 24 h and 30-day all-cause mortality as well as the customary safety endpoints.
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Combat-related blast trauma results in massive tissue injury and tends to involve multiple systems. Further, an acute measure of injury severity based on underlying biological mechanisms may be important for the triage and treatment of these types of patients. We hypothesized that urinary biomarkers (UBs) would reflect severity of injury and that they would be elevated for blast injuries compared with gunshot wounds (GSW) in a cohort of combat casualties. ⋯ After adjusting for injury severity score and time of UB draw, KIM-1 (2.80 vs. 2.31; P = 0.03) and LFABP (-1.11 vs. -1.92; P = 0.02) were significantly higher for patients with a blast mechanism of injury. There were no significant differences in UBs between burn and non-burn civilian trauma patients. Future studies are needed to understand the physiologic response to trauma and the extent that UBs reflect these underlying processes.