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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Background: Critical illness stemming from severe traumatic injury is a leading cause of morbidity and mortality worldwide and involves the dysfunction of multiple organ systems, driven, at least in part, by dysregulated inflammation. We and others have shown a key role for genetic predisposition to dysregulated inflammation and downstream adverse critical illness outcomes. Recently, we demonstrated an association among genotypes at the single-nucleotide polymorphism (SNP) rs10404939 in LYPD4 , dysregulated systemic inflammation, and adverse clinical outcomes in a broad sample of ~1,000 critically ill patients. ⋯ In the patient subset with genotypically dysregulated inflammation, our analysis suggested the co-localization to lipid rafts of LYPD4 and the complement receptor CD55, as well as the neurally related CNTNAP2 and RIMS4. Segregation of trauma patients based on genotype of the CD55 SNP rs11117564 showed distinct trajectories of organ dysfunction and systemic inflammation despite similar demographics and injury characteristics. Conclusion: These analyses define novel interactions among SNPs that could enhance our understanding of the response to traumatic injury and critical illness.
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Observational Study
Impact of ABCC8 and TRPM4 genetic variation in central nervous system dysfunction associated with pediatric sepsis.
Background: Sepsis-associated brain injury is associated with deterioration of mental status, persistent cognitive impairment, and morbidity. The SUR1/TRPM4 channel is a nonselective cation channel that is transcriptionally upregulated in the central nervous system with injury, allowing sodium influx, depolarization, cellular swelling, and secondary injury. We hypothesized that genetic variation in ABCC8 (SUR1 gene) and TRPM4 would associate with central nervous system dysfunction in severe pediatric sepsis. ⋯ Structural mapping showed that rare variants concentrated in the nucleotide-binding domains of ABCC8 and N-terminal melastatin homology region of TRPM4. Conclusion : This study suggests a role for the ABCC8/TRPM4 channel in central nervous system dysfunction in severe pediatric sepsis. Although exploratory, the lack of therapies to prevent or mitigate central nervous system dysfunction in pediatric sepsis warrants further studies to clarify the mechanism and confirm the potential protective effect of these rare ABCC8/TRPM4 variants.
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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 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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Background: 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. ⋯ Interpretation: Among 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 mechanical ventilation 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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Pelvic fractures are severe traumatic injuries often accompanied by potentially fatal massive bleeding. Rapid control of hemorrhages in prehospital emergency settings is critical for improving outcomes in traumatic bleeding. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a promising technique for controlling active bleeding from pelvic fractures. ⋯ This paper provides a comprehensive overview of the initial management of noncompressive trunk hemorrhage caused by pelvic fractures, introduces the technical principles and developments of REBOA, and explores its extensive application in prehospital emergency care. It delves into the operational details and outlines strategies for effectively managing potential complications. We aim to offer a theoretical framework for the future utilization of REBOA in managing uncontrollable hemorrhage associated with pelvic fractures in prehospital emergencies.