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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Sepsis is a life-threatening organ dysfunction initiated by a dysregulated response to infection, with imbalanced inflammation and immune homeostasis. Macrophages play a pivotal role in sepsis. N-[1-(1-oxopropyl)-4-piperidinyl]-N'-[4-(trifluoromethoxy)phenyl)-urea (TPPU) is an inhibitor of soluble epoxide hydrolase (sEH), which can rapidly hydrolyze epoxyeicosatrienoic acids (EETs) to the bio-inactive dihydroxyeicosatrienoic acids. TPPU was linked with the regulation of macrophages and inflammation. Here, we hypothesized that sEH inhibitor TPPU ameliorates cecal ligation and puncture (CLP)-induced sepsis by regulating macrophage functions. ⋯ sEH inhibitor TPPU ameliorates cecal ligation and puncture-induced sepsis by regulating macrophage functions, including improved phagocytosis and reduced inflammatory response. Our data indicate that sEH inhibition has potential therapeutic effects on polymicrobial-induced sepsis.
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Multicenter Study
Pharmacokinetics, Pharmacodynamics and Safety of Nivolumab in Patients With Sepsis-induced immunosuppression: A multicenter, open-label phase 1/2 study.
Sepsis often induces an immunosuppressive state, which is associated with high mortality rates. Immunostimulation may be beneficial for sepsis. We investigated the pharmacokinetics, pharmacodynamics, and safety of nivolumab, a human programmed death-1 immune checkpoint inhibitor approved for the treatment of several cancers. ⋯ A single dose of 960 mg nivolumab appeared to be well tolerated and sufficient to maintain nivolumab blood concentrations. Both 480 mg and 960 mg nivolumab seemed to improve immune system indices over time.
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Comparative Study
Pharmacokinetics of Tranexamic Acid Given as an Intramuscular Injection Compared to Intravenous Infusion in a Swine Model of Ongoing Hemorrhage.
Tranexamic acid (TXA) improves survival in traumatic hemorrhage, but difficulty obtaining intravenous (IV) access may limit its use in austere environments, given its incompatibility with blood products. The bioavailability of intramuscular (IM) TXA in a shock state is unknown. We hypothesized that IM and IV administration have similar pharmacokinetics and ability to reverse in vitro hyperfibrinolysis in a swine-controlled hemorrhage model. ⋯ The pharmacokinetics of IM TXA were similar to IV TXA during hemorrhagic shock in our swine model. IV administration resulted in a higher serum concentration only during the infusion, but all levels were able to successfully correct in vitro hyperfibrinolysis. There was no difference in total body exposure to equal doses of TXA between the two routes of administration. IM TXA may prove beneficial in scenarios where difficulty establishing dedicated IV access could otherwise limit or delay its use.
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Multicenter Study Observational Study
Venous-To-Arterial Carbon Dioxide Partial Pressure Difference: Predictor of Septic Patient Prognosis Depending on Central Venous Oxygen Saturation.
This study aimed to assess the viability of using the venous-to-arterial carbon dioxide partial pressure difference (P(v-a)CO2) to predict clinical worsening of septic shock, depending on central venous oxygen saturation (ScvO2). The prospective, observational, multicentric study conducted in three intensive care units (ICUs) included all patients with a septic shock episode during the first 6 h, with 122 patients assessed. Clinical worsening was defined as an increase of sequential organ failure assessment (SOFA) scores ≥1 (ΔSOFA ≥1) within 2 days. ⋯ ROC analysis confirmed that Lac [1-6] and P(v-a)CO2 [1-6] were significantly associated with ΔSOFA at least 1, whereas ScvO2 [1-6] was not. Finally, ΔSOFA at least 1 was associated with higher 28-day (76% vs. 10%, P = 0.001) and ICU (83% vs. 12%, P = 0.001) mortality rates, which were higher in patients with P(v-a)CO2 [1-6] more than 5.8 mmHg (57% vs. 33%; P = 0.012). In conclusion, P(v-a)CO2 may help predict outcomes for septic shock patients regardless of ScvO2 values.
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Vitamin D deficiency is associated with various cardiovascular diseases, including sudden cardiac arrest (SCA). Profound cardiogenic shock is associated with morbidity and mortality in patients with SCA. This study investigated the association of vitamin D deficiency with profound cardiogenic shock in patients resuscitated from SCA. ⋯ Severe vitamin D deficiency was strongly associated with profound cardiogenic shock and mortality in patients resuscitated from SCA.