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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Cardiopulmonary bypass (CPB), an extracorporeal method necessary for the surgical correction of complex congenital heart defects, incites significant inflammation that affects vascular function. These changes are associated with alterations in cellular metabolism that promote energy production to deal with this stress. Utilizing laser-doppler perfusion monitoring coupled with iontophoresis (LDPMI) in patients undergoing corrective heart surgery, we hypothesized that temporal, untargeted metabolomics could be performed to assess the link between metabolism and vascular function. ⋯ Correlation of metabolic profiles with endothelial-dependent (acetylcholine, ACh) or endothelial-independent (sodium nitroprusside, SNP) vascular reactivity identified purine metabolism being most consistently associated with either vascular response. Concerning ACh-mediated responses, acetylcarnitine levels were most strongly associated, while glutamine levels were associated with both ACh and SNP responsiveness. These data provide insight into the metabolic landscape of children undergoing CPB for corrective heart surgery and provide detail into how these metabolites relate to physiological aberrations in vascular function.
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Hemodynamic support using vasoactive agents is a mainstay in the management of patients with pediatric Fluid-Refractory Septic Shock (FRSS). However, evidence supporting the appropriate choice of vasoactive agent is limited. This study aimed to perform a systematic review and meta-analysis on the effect of different first-line vasoactive strategies on mortality in pediatric FRSS. ⋯ Of the 26,284 identified articles, 13 were included, for a total of 997 children. Twelve studies included 748 patients receiving a single vasoactive agent. Of these, 361 received dopamine, 271 epinephrine, and 116 norepinephrine. Overall pooled mortality for patients receiving a single vasoactive was 12% (95% CI 6-21%) of which 11% (95% CI 3-36%) for patients receiving dopamine, 17% (95% CI 6-37%) for epinephrine, 7% (95% CI 1-48%) for norepinephrine. Four first-line dopamine (176 patients) and first-line epinephrine (142 patients): dopamine showed a tendency towards higher mortality (PR 1.38, 95% CI 0.81-2.38) and a significant higher need for mechanical ventilation (MV) (PR 1.12, 95% CI 1.02-1.22).InterpretationAmong children with FRSS receiving a single vasoactive agent, norepinephrine was associated with the lowest mortality rate. Comparing dopamine and epinephrine, patients receiving epinephrine needed less MV and showed a trend for lower mortality rate. Further research is needed to better delineate the first-line vasoactive agent in this population.
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Previous preclinical studies have demonstrated a pathobiome after traumatic injury; however, the impact of post-injury sepsis on gut epithelial permeability and bacterial translocation remains unknown. We hypothesized that polytrauma with post-injury pneumonia would result in impaired gut permeability leading to specific blood microbiome arrays. ⋯ Multicompartmental trauma with post-injury pneumonia results in increased intestinal permeability and bacteremia with a unique blood biome, with sexual dimorphisms evident in the blood biome composition. These findings suggest that post-injury sepsis has clinical significance and could influence outcomes after severe trauma and critical illness.
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Infection of wounds delays healing, increases treatment costs, and leads to major complications. Current methods to manage such infections include antibiotic ointments and antimicrobial wound dressings, both of which have significant drawbacks, including frequent reapplication and contribution to antimicrobial resistance. In this work we developed wound dressings fabricated with a medical-grade polyurethane coating composed of natural plant secondary metabolites, cinnamaldehyde and alpha terpineol. ⋯ Our antimicrobial wound dressings reduced the burden of clinically relevant bacteria more than commercial antimicrobial wound dressings. In an in vivo infected burn wound model, our coatings performed as well or better than bacitracin. We anticipate that our wound dressings would be useful for the treatment of various types of acute and chronic wounds.
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Restoration of mesenteric lymphatic microcirculation is crucial for alleviating severe hemorrhagic shock-induced death. Exercise preconditioning (EP) enhances adaptability and resistance to injury and disease. The mitochondria-associated endoplasmic reticulum membrane (MAM) plays a crucial role in the energy and information exchange between the two organelles. ⋯ Importantly, treatment with 2-APB (IP3R1 inhibitor) or VBIT-12 (VDAC1 inhibitor) prolonged the survival time, improved mesenteric lymphatic contractility in vivo, ameliorated the MAM ultrastructure injury, and decreased the IP3R1 or VDAC1 expressions in LSMCs in rats following hemorrhagic shock. In contrast, the administration of drinking water containing CdCl2 (IP3R1 activator) abolished the beneficial effect of EP on hemorrhagic shock. Taken together, the protective effect of EP on lymphatic contractility following hemorrhagic shock was achieved by improving MAM in LSMCs.