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 hemolytic-uremic syndrome (HUS) is a thrombotic microangiopathy which can occur as a severe systemic complication after an infection with Shiga-toxin-(Stx)-producing Escherichia coli (STEC). Elevated levels of proinflammatory cytokines associated with the classical nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) signaling pathway were detected in the urine of HUS patients. Thus, we hypothesize that the immune response of the infected organism triggered by Stx can affect the kidneys and contributes to acute kidney injury. ⋯ In kidneys of mice subjected to Stx or sham-treated mice, protein or gene expression analyses were performed to assess the expression of receptors activating the classical and non-canonical pathway, such as Fn14 and CD40, levels of NF-κB1/RelA and NF-κB2/RelB including its upstream signaling proteins, and expression of cytokines as target molecules of both pathways. In line with a higher expression of Fn14 and CD40, we detected an enhanced translocation of NF-κB1 and RelA as well as NF-κB2 and RelB into the nucleus accompanied by an increased gene expression of the NF-κB1-target cytokines Ccl20, Cxcl2, Ccl2, Cxcl1, IL-6, TNF-α, Cxcl10, and Ccl5, indicating an activation of the classical and non-canonical NF-κB pathway. Thereby, we provide, for the first time, in vivo evidence for an involvement of both NF-κB signaling pathways in renal pathophysiology of STEC-HUS.
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Recent data suggests improved outcomes among cardiac intensive care unit (CICU) patients treated with norepinephrine, especially patients with severe shock. We aimed to describe the association between norepinephrine and mortality in CICU patients with severe shock, defined as those requiring high-dose vasopressors (HDV). ⋯ Mortality is high among CICU patients requiring HDV, and rises with increasing vasopressor requirements. Use of NE was associated with lower mortality among patients requiring HDV, but not among those without HDV, implying that patients with more severe shock may benefit from preferential use of NE.
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Sepsis-associated acute kidney injury (SA-AKI) is a common problem in critically ill patients and is associated with high morbidity and mortality. Early prediction of the survival of hospitalized patients with SA-AKI is necessary, but a reliable and valid prediction model is still lacking. ⋯ Our SAKI model has predictive value for in-hospital mortality of SA-AKI in critically ill patients and outperforms generic scores.
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We sought to review the pharmacology of vasoactive therapy and fluid administration in sepsis and septic shock, with specific insight into the physiologic interplay of these agents. A PubMed/MEDLINE search was conducted using the following terms (vasopressor OR vasoactive OR inotrope) AND (crystalloid OR colloid OR fluid) AND (sepsis) AND (shock OR septic shock) from 1965 to October 2020. ⋯ Current guidelines are not in alignment with the data available, which suggests a potential benefit from low-dose fluid administration and early vasopressor exposure. Future data must account for the impact of both of these pharmacotherapies when assessing clinical outcomes and should assess personalization of therapy based on the possible interaction.
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Cardiac arrest (CA) is recognized as a life-threatening disease; however, the initial resuscitation success rate has increased due to advances in clinical treatment. Levosimendan has shown potential benefits in CA patients. However, its exact function on intestinal and systemic circulation in CA or post-cardiac arrest syndrome (PCAS) remained unclear. This study preliminarily investigated the link between dynamic changes in intestine and systemic hemodynamics post-resuscitation after levosimendan administration. ⋯ Levosimendan significantly reduced the cardiac injury and corrected the metabolic status in an experimental rat model of ventricular fibrillation induced CA and cardiopulmonary resuscitation. Levosimendan may ameliorate PCAS-induced intestinal microcirculation dysfunction, partly independent of its effects on macrocirculation.