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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Despite advancements in critical care and resuscitation, traumatic injuries are one of the leading causes of death around the world and can bring about long-term disabilities in survivors. One of the primary causes of death for trauma patients are secondary phase complications that can develop weeks or months after the initial insult. These secondary complications typically occur because of systemic immune dysfunction that develops in response to injury, which can lead to immunosuppression, coagulopathy, multiple organ failure, unregulated inflammation, and potentially sepsis in patients. ⋯ In this review, we will discuss the role of EVs in the posttrauma pathologies that arise after burn injuries, trauma to the central nervous system, and infection. In addition, we will examine the use of EVs as biomarkers for predicting late-stage trauma outcomes and as therapeutics for reversing the pathological processes that develop after trauma. Overall, EVs have emerged as critical mediators of trauma-associated pathology and their use as a therapeutic agent represents an exciting new field of biomedicine.
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Sepsis is a major health issue and a leading cause of death in hospitals globally. The treatment of sepsis is largely supportive, and there are no therapeutics available that target the underlying pathophysiology of the disease. The development of therapeutics for the treatment of sepsis is hindered by the heterogeneous nature of the disease. ⋯ However, there has been limited studies of immune cell function during sepsis and even fewer correlating omics and biomarker alterations to functional consequences. In this review, we will discuss how the heterogeneity of sepsis and associated immune cell phenotypes result from changes in the omic makeup of cells and its correlation with leukocyte dysfunction. We will also discuss how emerging techniques such as in silico modeling and machine learning can help in phenotyping sepsis patients leading to precision medicine.
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Review
Variables Influencing the Differential Host Response to Burns in Pediatric and Adult Patients.
Burn injury is a significant source of morbidity and mortality in the pediatric population. Although 40,000 pediatric patients in the United States are admitted to the hospital with burn wounds annually, significant differences exist in the management and treatment of these patients, even among highly specialized burn centers. ⋯ This review compares and contrasts a wide array of physiologic and immune responses between children and adults after burn injury. Such a review elucidates where robust research has been conducted, where adult research is applicable to pediatric patients, and where additional pediatric burn research needs to be conducted.
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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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Sepsis is a life-threatening organ dysfunction, caused by dysregulation of the host response to infection. To understand the underlying mechanisms of sepsis, the vast spectrum of extracellular vesicles (EVs) is gaining importance in this research field. A connection between EVs and sepsis was shown in 1998 in an endotoxemia pig model. ⋯ Extracellular vesicles of different cellular origin, such as leucocytes, macrophages, platelets, and granulocytes, have been suggested as potential sepsis biomarkers. They ensure the diagnosis of sepsis earlier than classical clinical inflammation markers, such as C-reactive protein, leucocytes, or IL-6. This review summarizes the three roles of EVs in sepsis-mediator/inducer, biomarker, and therapeutic tool.