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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Observational Study
Shock-Induced Endothelial Dysfunction is Present in Patients With Occult Hypoperfusion After Trauma.
Shock-induced endothelial dysfunction, evidenced by elevated soluble thrombomodulin (sTM) and syndecan-1 (Syn-1), is associated with poor outcomes after trauma. The association of endothelial dysfunction and overt shock has been demonstrated; it is unknown if hypoperfusion in the setting of normal vital signs (occult hypoperfusion [OH]) is associated with endothelial dysfunction. We hypothesized that sTM and Syn-1 would be elevated in patients with OH when compared to patients with normal perfusion. ⋯ Arrival OH was associated with elevated sTM and Syn-1, indicating endothelial dysfunction. Treatments aiming to stabilize the endothelium may be beneficial for injured patients with evidence of hypoperfusion, regardless of vital signs.
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Comparative Study
Distinctive Biomarker Features in The Endotheliopathy of COVID-19 and Septic Syndromes.
Endotheliopathy is a key element in COVID-19 pathophysiology, contributing to both morbidity and mortality. Biomarkers distinguishing different COVID-19 phenotypes from sepsis syndrome remain poorly understood. ⋯ COVID-19 patients present with increased circulating endothelial stress products, complement activation, and fibrinolytic dysregulation, associated with disease severity. COVID-19 endotheliopathy differs from SS, in which endothelial damage is also a critical feature of pathobiology. These biomarkers could help to stratify the severity of COVID-19 disease and may also provide information to guide specific therapeutic strategies to mitigate endotheliopathy progression.
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Vitamin C combined with hydrocortisone is increasingly being used to treat septic patients, even though this treatment regimen is based on questionable evidence. When used, a marked effect on key players of innate immunity would be expected, as sepsis is featured by a dysregulated immune response. Here, we explored the effect of vitamin C and hydrocortisone alone and combined, in an ex vivo human whole-blood model of Escherichia coli- or Staphylococcus aureus-induced inflammation. ⋯ The oxidative burst of monocytes and granulocytes was reduced for both drugs alone and their combination, (ranging 8-19%, P < 0.05). Using S. aureus, neither of the drugs, alone nor in combination, had any effects on the nine biomarkers. In conclusion, despite the limitation of the ex vivo model, the effect of vitamin C and hydrocortisone on bacteria-induced inflammatory response in human whole blood is limited and following the clinical data.
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Matrix Metalloproteinases (MMP) respond to tissue damage during sepsis. Higher plasma concentrations of MMPs and the tissue-inhibitor of matrix metalloproteinases (TIMP) have been reported in sepsis compared with healthy controls. The objective of this study was to examine if plasma levels of MMP-3, MMP-9, and TIMP-1 associate with mortality and organ dysfunction during sepsis. ⋯ Elevated plasma concentrations of TIMP-1 associate with organ dysfunction and mortality in sepsis. Higher plasma levels of MMP-3 associate with shock and mortality. Plasma MMP and TIMP-1 may warrant further investigation as emerging sepsis theragnostic biomarkers.
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Randomized Controlled Trial Multicenter Study
Biomarker Analysis for Combination Therapy of Vitamin C and Thiamine In Septic Shock: A Post-HOC Study of The Atess Trial.
We evaluated the effects of vitamin C and thiamine administration on biomarkers in patients with septic shock. ⋯ Vitamin C and thiamine administration during the early phase of septic shock did not significantly change prognostic biomarker levels of IL-6, IL-10, AP2, and S100β.