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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Sepsis is defined as a life-threatening organ dysfunction, caused by a dysregulated host response to an infection and can progress to septic shock, which represents a major challenge in critical care with a high mortality rate. Currently, there is no definitive treatment available for the dysregulated immune response in sepsis. Therefore, a better understanding of the pathophysiological mechanisms may be useful for elucidating the molecular basis of sepsis and may contribute to the development of new therapeutic strategies. ⋯ This review addresses the main functionality of CB1 and CB2 in sepsis, which can contribute to a better understanding about the pathophysiology of sepsis. Specifically, we discuss the role of CB1 in the cardiovascular system which is one of the biological systems that are strongly affected by sepsis and septic shock. We are also reviewing the role of CB2 in sepsis, specially CB2 activation, which exerts anti-inflammatory activities with potential benefit in sepsis.
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Myeloid-derived suppressor cells (MDSCs) are a heterogenous population of immature myeloid cells hallmarked by their potent immunosuppressive function in a vast array of pathologic conditions. MDSCs have recently been shown to exhibit marked expansion in acute inflammatory states including traumatic injury, burn, and sepsis. Although MDSCs have been well characterized in cancer, there are significant gaps in our knowledge of their functionality in trauma and sepsis, and their clinical significance remains unclear. ⋯ Whether MDSCs may serve as the target for novel therapeutics or an important biomarker in trauma and sepsis is yet to be determined. In this review, we will discuss the current understanding of MDSCs within the context of specific traumatic injury types and sepsis. To improve delineation of their functional role, we propose a systemic approach to MDSC analysis including phenotypic standardization, longitudinal analysis, and expansion of clinical research.
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"Cytokine storm" has been used to implicate increased cytokine levels in the pathogenesis of serious clinical conditions. Similarities with Severe Acute Respiratory Syndrome Coronoavirus-2 (SARS CoV-2) and the 2012 Middle Eastern Respiratory Syndrome led early investigators to suspect a "cytokine storm" resulting in an unregulated inflammatory response associated with the significant morbidity and mortality induced by SARS CoV-2. The threshold of blood cytokines necessary to qualify as a "cytokine storm" has yet to be defined. ⋯ The misleading term "cytokine storm" implies increased blood levels of cytokines are responsible for a grave clinical condition. Not all inflammatory conditions resulting in worsened disease states are correlated with significantly elevated cytokine levels, despite an association with the term "cytokine storm". "Cytokine storm" should be removed from the medical lexicon since it does not reflect the mediators driving the disease nor does it predict which diseases will respond to cytokine inhibitors.
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Thrombin is the central coagulation enzyme that catalyzes the conversion of fibrinogen to form insoluble fibrin blood clots. In vivo, thrombin production results from the concerted effort of plasma enzymatic reactions with essential contributions from circulating and vessel wall cells. ⋯ Thus, understanding determinants of thrombin generation following traumatic injury is of high clinical importance. This review will focus on patterns and mechanisms of thrombin generation in severely injured patients, the role of fluid resuscitation in modulating thrombin generation and implications for outcomes.
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In the last few decades, obesity became one of the world's greatest health challenges reaching a size of global epidemic in virtually all socioeconomic statuses and all age groups. Obesity is a risk factor for many health problems and as its prevalence gradually increases is becoming a significant economic and health burden. In this manuscript we describe how normal respiratory and cardiovascular physiology is altered by obesity. We review past and current literature to describe how obesity affects outcomes of patients facing critical illnesses and discuss some controversies related to this topic.