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 and septic shock usually show a high mortality rate and frequently need of intensive care unit admissions. After fluid resuscitation, norepinephrine (NE) is the first-choice vasopressor in septic shock patients. However, high-NE doses are associated with increased rates of adverse effects and mortality. ⋯ Only few clinical data actually support selepressin administration in this setting. Here, we review the current literature on this topic analyzing some pathophysiological aspects, the rationale about the use of NAV, the possible use of selepressin differentiating animal, and human studies. Various issues remain unresolved and future trials should be focused on early interventions based on a multimodal activation of the vasopressive pathways using both alpha and V1A receptors pathways.
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Extracellular vesicles (EVs) are nano-sized membrane-bound particles containing biologically active cargo molecules. The production and molecular composition of EVs reflect the physiological state of parent cells, and once released into the circulation, they exert pleiotropic functions via transferring cargo contents. Thus, circulating EVs not only serve as biomarkers, but also mediators in disease processes or injury responses. ⋯ Taken together, these data suggest that burn injury promotes the production of EVs containing unique cargo proteins in a time-dependent manner; the response correlates with injury severity and worsened clinical outcomes. Functionally, burn EVs serve as a potent mediator capable of reducing endothelial barrier resistance and impairing junction integrity, a pathophysiological process underlying burn-associated tissue dysfunction. Thus, further in-depth characterization of circulating EVs will contribute to the development of new prognostic tools or therapeutic targets for advanced burn care.
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Observational Study
Impaired Lymphocyte Responses in Pediatric Sepsis Vary by Pathogen Type and are Associated with Features of Immunometabolic Dysregulation.
Sepsis is the leading cause of death in hospitalized children worldwide. Despite its hypothesized immune-mediated mechanism, targeted immunotherapy for sepsis is not available for clinical use. ⋯ Pediatric sepsis patients exhibit a complex, dynamic physiologic state characterized by impaired T cell function and immunometabolic dysregulation which varies by pathogen type.
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Functional Transcriptomic Studies of Immune Responses and Endotoxin Tolerance In early Human Sepsis.
Limited studies have functionally evaluated the heterogeneity in early ex vivo immune responses during sepsis. Our aim was to characterize early sepsis ex vivo functional immune response heterogeneity by studying whole blood endotoxin responses and derive a transcriptional metric of ex vivo endotoxin response. ⋯ An attenuated ex vivo endotoxin response in early sepsis is associated with greater host in vivo inflammation and a worse clinical outcome.
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Randomized Controlled Trial
Modulation of LTCC Pathways by A Melusin Mimetic Increases Ventricular Contractility During LPS-Induced Cardiomyopathy.
Sepsis-induced cardiomyopathy is commonplace and carries an increased risk of death. Melusin, a cardiac muscle-specific chaperone, exerts cardioprotective function under varied stressful conditions through activation of the AKT pathway. The objective of this study was to determine the role of melusin in the pathogenesis of lipopolysaccharide (LPS)-induced cardiac dysfunction and to explore its signaling pathway for the identification of putative therapeutic targets. ⋯ This study identifies AKT / Melusin as a key pathway for preserving cardiac function following LPS challenge. The cell-permeable mimetic peptide (R7W-MP) represents a putative therapeutic for sepsis-induced cardiomyopathy.