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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Results from preclinical sepsis studies using rodents are often criticized as not being reproducible in humans. Using a murine model, we previously reported that visceral adipose tissues (VAT) are highly active during the acute inflammatory response, serving as a major source of inflammatory and coagulant mediators. The purpose of this study was to determine whether these findings are recapitulated in patients with sepsis and to evaluate their clinical significance. ⋯ In another cohort of septic patients stratified by incidence of AKI, circulating PAI-1 levels were higher in those with versus without AKI, thus extending these findings beyond intra-abdominal cases. This study is the first to translate upregulation of VAT mediators in sepsis from mouse to human. Collectively, the data suggest that development of AKI in septic patients is associated with high plasma levels of PAI-1, likely derived from resident cells within VAT.
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Recent studies have suggested the female hypercoaguable state may have a protective effect in trauma. However, whether this hypercoagulable profile confers a survival benefit in massively transfused trauma patients has yet to be determined. We hypothesized that females would have better outcomes than males after traumatic injury that required massive transfusion protocol (MTP). ⋯ Sex differences in coagulation profile do not result in a survival advantage for females when MTP is required.
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Observational Study
The Prognostic Value of Lactate in Cardiac Intensive Care Unit Patients with Cardiac Arrest and Shock.
Lactate is a prognostic marker in critically ill patients, although currently available illness severity scores do not include lactate as a predictive parameter. We sought to describe the association between lactate and hospital mortality in patients admitted to the cardiac intensive care unit (CICU) with cardiac arrest (CA) and shock. ⋯ Admission lactate levels are strongly associated with increased hospital mortality among CICU patients, including those with and without CA or shock. The prognostic value of lactate levels is independent of established ICU prognostic scores and dependent on admission diagnosis, which may help inform clinicians caring for CICU patients.
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Evidence implying that metabolism reprogramming plays an important role in the regulation of sepsis is increasing; however, whether it has a similar role in septic organ dysfunction remains unclear. Here, we provide evidence to support a new role of uncoupling protein-2 (UCP2)-regulated Warburg effect, i.e., aerobic glycolysis, in promoting mitochondrial injury in the kidney. ⋯ These results provide insights on a new mechanism of metabolic regulation of mitochondrial injury and the importance of targeting aerobic glycolysis for the treatment of septic acute kidney injury.