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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Despite the known deleterious effects of obesity, clinical data indicate that overweight or obese patients experience higher rates of sepsis survival compared to normal and underweight patients; a phenomenon called the obesity paradox. Results from preclinical sepsis studies have not been able to replicate these findings. The objective of this study was to test the existence of the obesity paradox in a murine model of cecal slurry (CS)-induced sepsis with insulin-resistant diet-induced obese mice. ⋯ This murine study corroborates clinical data that obesity confers a survival benefit in sepsis, albeit at the expense of more significant organ injury. The mechanisms promoting survival in the obese remain unknown; however, this model appears to be well-poised to begin answering this question. Differences in glucose utilization are a novel target to investigate this paradox.
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Review
Sepsis-Induced Myopathy and Gut Microbiome Dysbiosis: Mechanistic Links and Therapeutic Targets.
Sepsis is currently defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The skeletal muscle system is among the host organ systems compromised by sepsis. The resulting neuromuscular dysfunction and impaired regenerative capacity defines sepsis-induced myopathy and manifests as atrophy, loss of strength, and hindered regeneration after injury. ⋯ The gut microbiome is an immunological and homeostatic entity that interacts with and controls end-organ function, including the skeletal muscle system. Sepsis induces alterations in the gut microbiota composition, which is globally termed a state of "dysbiosis" for the host compared to baseline microbiota composition. In this review, we critically evaluate existing evidence and potential mechanisms linking sepsis-induced myopathy with gut microbiota dysbiosis.
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Acute traumatic coagulopathy (ATC) is an endogenous impairment in hemostasis that often contributes to early mortality after trauma. Endothelial glycocalyx damage is associated with trauma-induced coagulation abnormalities; however, the specific relationship between hyaluronan (HA), a key glycocalyx constituent, and ATC has not been evaluated. ⋯ Shed HA is associated with early coagulation abnormalities in trauma patients, which may contribute to worse outcomes. These findings highlight the need for additional studies to evaluate the mechanistic role of HA in ATC.
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Randomized Controlled Trial Multicenter Study
Biomarker Analysis for Combination Therapy of Vitamin C and Thiamine In Septic Shock: A Post-HOC Study of The Atess Trial.
We evaluated the effects of vitamin C and thiamine administration on biomarkers in patients with septic shock. ⋯ Vitamin C and thiamine administration during the early phase of septic shock did not significantly change prognostic biomarker levels of IL-6, IL-10, AP2, and S100β.
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Microglial activation is a vital process in the neuroinflammatory response induced by I/R injury. It has been reported that myocyte enhancer factor (MEF)2D expression in activated microglia is associated with microglia-induced inflammatory responses and plays an important role in neuronal survival. This research aimed to investigate the role and mechanism of MEF2D in microglial activation and neuroinflammation in cerebral I/R in vitro and in vivo. ⋯ These results indicate that MEF2D is a necessary molecule for neuroinflammation regulation and neuronal injury in cerebral ischemia.