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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Observational Study
Demographics to define pediatric burn patients at risk of adverse outcomes.
Background: There is currently no standard definition of a severe burn in the pediatric patient population to identify those at higher risk of infectious complications. Our aim was to correlate total burn surface area (TBSA), burn depth, and type of burn injury to nosocomial infection rates and systemic immune system responses to better define risk factors associated with adverse outcomes. Methods: A prospective observational study at a single-center, quaternary-care, American Burn Association-verified pediatric burn center was conducted from 2016 to 2021. ⋯ Both burn injury characteristics were also associated with a significant increase in unstimulated IL-6 and IL-10 and soluble immunoregulatory checkpoint proteins. We observed a significant decrease in soluble B- and T-lymphocyte attenuator for those with a flame injury, but there were no other differences between flame injury and scald/contact burns in terms of innate and adaptive immune function. Conclusion: Burns with ≥20% TBSA or ≥5% full thickness in pediatric patients are associated with systemic immune dysfunction and increased risk of nosocomial infections.
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Background: Obesity increases the risk for morbidity and mortality after trauma. These complications are associated with profound vascular damage. Traumatic hemorrhage acutely attenuates vascular responsiveness, but the impact of obesity on this dysfunction is not known. ⋯ The attenuated vascular responsiveness after hemorrhage is absent in obese rats, while the elevated vascular inflammation persists. A HF diet amplifies the arterial inflammation after hemorrhage. Altered vascular responsiveness and vascular inflammation may contribute to worse outcomes in obese trauma patients.
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Sepsis and trauma remain the leading causes of morbidity and mortality. Our understanding of the molecular pathogenesis in the development of multiple organ dysfunction in sepsis and trauma has evolved as more focus is on secondary injury from innate immunity, inflammation, and the potential role of endogenous danger molecules. Studies of the past several decades have generated evidence for extracellular RNAs (exRNAs) as biologically active mediators in health and disease. Here, we review studies on plasma exRNA profiling in mice and humans with sepsis and trauma, the role and mode of action by exRNAs, such as ex-micro(mi)RNAs, in host innate immune response, and their potential implications in various organ injury during sepsis and trauma.
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Background: Immunosuppression is critically involved in the development of sepsis and is closely associated with poor outcomes. The novel role of the anti-inflammatory cytokine IL-35 in sepsis was examined. Methods: Sepsis was induced by in C57BL/6 mice cecal ligation and puncture (CLP). ⋯ Sepsis-induced autophagy activation was protective in effector CD4 + T cells and was blocked by rIL-35. The inhibitory effect of IL-35 on autophagy was observed in activated effector CD4 + T cells in vitro , and this effect was mediated by restricting high mobility group box-1 protein (HMGB1) translocation. Conclusion: IL-35 is an immunosuppressive cytokine that impairs CD4 + T-cell proliferation and differentiation in sepsis, and the effect might be mediated by reducing HMGB1-dependent autophagy.
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There is growing appreciation that skeletal muscle is a fully functional component of the body's innate immune system with the potential to actively participate in the host response to invading bacteria as opposed to being a passive target. In this regard, skeletal muscle in general and myocytes specifically possess an afferent limb that recognizes a wide variety of host pathogens via their interaction with multiple classes of cell membrane-bound and intracellular receptors, including toll-like receptors, cytokine receptors, NOD-like receptors, and the NLRP inflammasome. ⋯ Moreover, because there are important differences, this review focuses specifically on systemic infection and inflammation as opposed to the response of muscle to direct injury and various types of muscular dystrophies. To date, however, there are few definitive muscle-specific studies that are necessary to directly address the relative importance of muscle-derived immune activation as a contributor to either the systemic immune response or the local immune microenvironment within muscle during sepsis and the resultant downstream metabolic disturbances.