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
-
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.
-
Multicenter Study
Incidence and Impact of Dysglycemia in Patients with Sepsis Under Moderate Glycemic Control.
Glycemic control strategies for sepsis have changed significantly over the last decade, but their impact on dysglycemia and its associated outcomes has been poorly understood. In addition, there is controversy regarding the detrimental effects of hyperglycemia in sepsis. To evaluate the incidence and risks of dysglycemia under current strategy, we conducted a preplanned subanalysis of the sepsis cohort in a prospective, multicenter FORECAST study. ⋯ In conclusion, a significantly high incidence of dysglycemia was observed in our sepsis cohort under moderate glycemic control. Late hyperglycemia in addition to early hypoglycemia was associated with poor outcomes at least in nondiabetic patients. More sophisticated approaches are necessary to reduce the incidence of these serious complications.
-
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.
-
Studies have shown nonlinear relationships between systolic blood pressure (SBP) and outcomes, with increased risk observed at both low and high blood pressure levels. However, the relationships between cumulative times at different SBP levels and outcomes in critically ill patients remain unclear. We hypothesized that an appropriate SBP level is associated with a decrease in adverse outcomes after intensive care unit (ICU) admission. ⋯ SBP at 120 mm Hg to 140 mm Hg was associated with decreased adverse outcomes. Randomized trials are required to determine whether the outcomes in critically ill patients improve with early maintenance of a SBP level at 120 mm Hg to 140 mm Hg.
-
Levels of the apoptosis regulator Fas ligand (FasL) are associated with severity of sepsis, but its association with the mortality of sepsis and necroptosis, a regulated cell death mechanism, is not yet clear. We aimed to assess the association of FasL level with outcomes of sepsis and receptor interacting protein kinase-3 (RIPK3), an essential necroptosis mediator, for determining the relationship between FasL and necroptosis. ⋯ The plasma level of FasL was associated with severity of sepsis and was predictive of mortality. However, it was not correlated with RIPK3 level.