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-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Genetic deletion of myosin light chain kinase (MLCK) reverses intestinal hyperpermeability and improves survival in a murine model of intra-abdominal sepsis. In an attempt to determine whether these findings could be translated using a more clinically relevant strategy, this study aimed to determine if pharmacologic inhibition of MLCK using the membrane permeant inhibitor of MLCK (PIK) improved gut barrier function and survival following sepsis. ⋯ Examination of jejunal tight junctions for potential mechanisms underlying increased leak permeability revealed that mice that received PIK had increased phosphorylated MLC without alterations in occludin, ZO-1, or JAM-A. PIK administration was not associated with significant differences in systemic or peritoneal bacterial burden, cytokines, splenic or Peyer's Patches immune cells or intestinal integrity. These results demonstrate that pharmacologic inhibition of MLCK unexpectedly increases mortality, associated with worsened intestinal permeability through the leak pathway, and suggest caution is required in targeting the gut barrier as a potential therapy in sepsis.
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Resuscitative endovascular balloon occlusion of the aorta (REBOA) allows for effective temporization of exsanguination from non-compressible hemorrhage (NCTH) below the diaphragm. However, the therapeutic window for aortic occlusion is time-limited given the ischemia-reperfusion injury generated. Significant effort has been put into translational research to develop new strategies to alleviate the ischemia-reperfusion injury and extend the application of endoaortic occlusion. ⋯ The objective of TRO is to reduce the degree of ischemia caused by complete aortic occlusion while providing control of distal hemorrhage. This review provides a synopsis of the concept of TRO, pre-clinical, translational experiences with TRO and early clinical outcomes. Early results from TRO strategies are promising; however, further studies are needed prior to large-scale implementation into clinical practice.
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Randomized Controlled Trial
Estrogen As A Safe Therapeutic Adjunct in Reducing The Inflammatory Storm in Trauma Hemorrhagic Shock Patients.
Trauma is a major cause of death and disability throughout the world. It is a leading cause of death with or without sepsis in about 50% of patients. Limited therapeutic options are available besides definitive care with a mortality benefit. ⋯ In conclusion, this preliminary study showed that intravenous estrogen therapy is safe and reduced the inflammatory insult due to trauma hemorrhagic shock. It may protect THS patients from sepsis-associated complications. Future clinical trials are required to study the efficacy and mechanistic pathway.
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Multicenter Study
Incidence and Impact of Dysglycemia in Patients with Sepsis Under Moderate Glycemic Control.
Glycemic control strategies for sepsis have changed significantly over the last decade, but their impact on dysglycemia and its associated outcomes has been poorly understood. In addition, there is controversy regarding the detrimental effects of hyperglycemia in sepsis. To evaluate the incidence and risks of dysglycemia under current strategy, we conducted a preplanned subanalysis of the sepsis cohort in a prospective, multicenter FORECAST study. ⋯ In conclusion, a significantly high incidence of dysglycemia was observed in our sepsis cohort under moderate glycemic control. Late hyperglycemia in addition to early hypoglycemia was associated with poor outcomes at least in nondiabetic patients. More sophisticated approaches are necessary to reduce the incidence of these serious complications.