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-associated encephalopathy (SAE) is a serious complication of sepsis, which is characterized by cognitive dysfunction, a poor prognosis, and high incidences of morbidity and mortality. Substantial levels of systemic inflammatory factors induce neuroinflammatory responses during sepsis, ultimately disrupting the central nervous system's (CNS) homeostasis. This disruption results in brain dysfunction through various underlying mechanisms, contributing further to SAE's development. ⋯ They serve an important regulatory role in CNS homeostasis and can be activated through multiple pathways. Consequently, activated microglia are involved in several pathogenic mechanisms related to SAE and play a crucial role in its development. This article discusses the role of microglia in neuroinflammation, dysfunction of neurotransmitters, disruption of the blood-brain barrier, abnormal control of cerebral blood flow, mitochondrial dysfunction, and reduction in the number of good bacteria in the gut as main pathogenic mechanisms of SAE and focuses on studies targeting microglia to ameliorate SAE to provide a theoretical basis for targeted microglial therapy for SAE.
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Randomized Controlled Trial
Acetate Ringer's Solution versus Normal Saline Solution in Sepsis: A Randomized, Controlled Trial.
Background: Normal saline solution (NSS) and Ringer's acetate solution (RAS) are commonly given to critically ill patients as a fundamental fluid therapy. However, the effect of RAS and NSS on sepsis patient outcomes remains unknown. Methods: We conducted a single-center prospective open-label parallel controlled trial to enroll adult patients (>18 years old) diagnosed with sepsis. ⋯ The patients in the NSS-only group had a longer invasive mechanical ventilation days and a trend toward the accumulation of serum chloride. Conclusion: This study observed no statistically significant difference on MAKE28 and secondary outcomes among sepsis patients receiving RAS and NSS. However, it is unclear whether the large amount of fluid resuscitation before ICU admission and carrier NSS narrowed the difference between BSSs and NSSs.
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Objective: Extracellular purines such as adenosine triphosphate (ATP), uridine triphosphate (UTP), and uridine diphosphate (UDP) and the ATP degradation product adenosine are biologically active signaling molecules, which accumulate at sites of metabolic stress in sepsis. They have potent immunomodulatory effects by binding to and activating P1 or adenosine and P2 receptors on the surface of leukocytes. Here we assessed the levels of extracellular purines, their receptors, metabolic enzymes, and cellular transporters in leukocytes of septic patients. ⋯ Conclusion: Because CD39 degrades ATP to adenosine monophosphate (AMP), the lower ATP levels in septic individuals may be the result of increased CD39 expression. This increased degradation of ATP did not lead to increased adenosine levels, which may be explained by the decreased expression of CD73, which converts AMP to adenosine. Altogether, our results demonstrate differential regulation of components of the purinergic system in PBMCs during human sepsis.