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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Hydrogen sulfide (H2S) has many beneficial biological properties, including the ability to promote vasodilation. It has been shown to be released from stem cells and increased by hypoxia. Therefore, H2S may be an important paracrine factor in stem cell-mediated intestinal protection. We hypothesized that H2S created through conventional pathways would be a critical component of stem cell-mediated intestinal protection after ischemic injury. ⋯ Knocking down conventional H2S-producing enzymes only impacted gas production in normoxic conditions. When cells were transfected in hypoxic conditions, as would be expected in the ischemic intestines, H2S gas was not depressed. These data, along with unchanged perfusion and histological injury parameters with conventional enzyme knockdown, would indicate that alternative H2S production pathways may be initiated during hypoxic and/or ischemic events.
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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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Patients who experience severe burn injuries face a massive inflammatory response resulting in hemodynamic and cardiovascular complications. Even after immediate and appropriate resuscitation, removal of burn eschar and covering of open areas, burn patients remain at high risk for serious morbidity and mortality. As a result of the massive fluid shifts following the initial injury, along with large volume fluid resuscitation, the cardiovascular system is critically affected. ⋯ The use of anabolic and anticatabolic agents has been shown to be beneficial for short- and long-term outcomes of burn survivors. Administration of propranolol (non-selective β-receptor antagonist) or oxandrolone (synthetic testosterone) for up to 12 months post-burn counteracts hypermetabolism during hospital stay and improves cardiac function. A comprehensive understanding of how burns lead to cardiac dysfunction and new therapeutic options could contribute to better outcomes in this patient population.
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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.