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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Introduction : COVID-19-induced coagulopathy (CIC) can increase the risk of thromboembolism without underlying clotting disorders, even when compared with other respiratory viruses. Trauma has a known association with hypercoagulability. Trauma patients with concurrent COVID-19 infection potentially have an even greater risk of thrombotic events. ⋯ Positive patients had longer median ICU LOS ( P = 0.0012) and total LOS ( P < 0.001). Conclusion : There were no increased rates of VTE complications between COVID-19-positive and -negative trauma patients, despite a longer time to initiation of chemoprophylaxis in the COVID-19-positive group. COVID-19-positive patients had increased ICU LOS, total LOS, and mortality, which are likely due to multifactorial causes but primarily related to their underlying COVID-19 infection.
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Studies in animal models of sepsis have elucidated an intricate network of signaling pathways that lead to the dysregulation of myocardial Ca 2+ handling and subsequently to a decrease in cardiac contractile force, in a sex- and model-dependent manner. After challenge with a lethal dose of LPS, male animals show a decrease in cellular Ca 2+ transients (ΔCa i ), with intact myofilament function, whereas female animals show myofilament dysfunction, with intact ΔCa i. Male mice challenged with a low, nonlethal dose of LPS also develop myofilament desensitization, with intact ΔCa i. ⋯ Myofilament dysfunction is due to hyperphosphorylation of troponin I, troponin T cleavage by caspase-3, and overproduction of cGMP by NO-activated soluble guanylate cyclase. Depleted, dysfunctional, or uncoupled mitochondria likely synthesize less ATP in both sexes, but the role of energy deficit is not clear. NO produced by NO synthase (NOS)-3 and mitochondrial NOSs, protein kinases and phosphatases, the processes of autophagy and sarco/endoplasmic reticulum stress, and β-adrenergic insensitivity may also play currently uncertain roles.
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Background : Cecal ligation and perforation (CLP) is currently considered the criterion standard model of sepsis; however, there are some deficiencies, such as low clinical relevance, inconsistency in severity grading, and an unknown proportion of CLP animals meeting the requirements of sepsis-3. Methods : Adult rats were randomly divided into the following three groups: modified CLP (M-CLP) group, CLP group, and sham group. The vital organ function of rats was evaluated 24 hours postoperatively by blood pressure, behavioral testing, histopathology, and blood test. ⋯ In addition, disease development and severity, which was indicated by the stable survival rates of model animals, were more stable in the M-CLP group. Conclusions : More rats could meet Sepsis-3 criteria with this novel surgical procedure, which may reduce the number of animals needed in preclinical sepsis experiments. This stable M-CLP model may contribute to the development of new therapies.
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Introduction: Cell-free DNA (CFDNA) has emerged as a prognostic biomarker in patients with sepsis. Circulating CFDNA is hypothesized to be associated with histones in the form of nucleosomes. In vitro, DNA activates coagulation and inhibits fibrinolysis, whereas histones activate platelets and are cytotoxic to endothelial cells. ⋯ Monotherapies may be improving survival by reducing blood bacterial loads, citrullinated histone-H3, and thrombin-antithrombin complexes, and improving protein C levels. Conclusions: Compared with saline- and combination-treated mice, administration of monotherapies to septic mice improved survival. These findings suggest that there may be a negative drug-drug interaction between DNase I and LMWH when DNase I is administered intraperitoneally in a murine model of polymicrobial abdominal sepsis.
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Introduction: Little is known regarding peripheral blood mononuclear cell telomere length (PBMC-TL) and response to traumatic injury. The objective of this study was to characterize the role of PBMC-TL in coagulation and clinical outcomes after injury. Methods: Plasma and buffy coats were prospectively collected from trauma patients and healthy volunteers. ⋯ Older patients in the bottom quartile of PBMC-TL had shorter lag time (2.78 min [2.33, 3.00] vs. 3.33 min [3.24, 3.89], P = 0.030) and were less likely to be discharged home (22% vs. 90%, P = 0.006) than those in the top quartile of PBMC-TL. Multivariable logistic regression models revealed both increased age and shorter PBMC-TL to be independent predictors of discharge disposition other than home. Conclusion: In older trauma patients, shorter PBMC-TL is associated with accelerated initiation of thrombin generation and lower likelihood of being discharged to home.