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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Aims: Targeted temperature management is recommended for at least 24 h in comatose survivors of in-hospital cardiac arrest (IHCA) after the return of spontaneous circulation; however, whether an extension for 72 h leads to better neurological outcomes is uncertain. Methods: We included data from the Qilu Hospital of Shandong University between July 20, 2019, and June 30, 2022. Unconscious patients who had return of spontaneous circulation lasting >20 consecutive min and received endovascular cooling (72 h) or normothermia treatment were compared in terms of survival-to-discharge and favorable neurological survival. ⋯ However, good neurological outcomes did not differ significantly. Before matching, Cox regression analysis, using mortality as the event, showed that extended endovascular cooling independently affected the survival of IHCA patients. Conclusions: Among comatose patients who had been resuscitated from IHCA, the use of endovascular cooling for 72 h might confer a benefit on survival-to-discharge.
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Recent research has revealed that aerobic glycolysis has a strong correlation with sepsis-associated pulmonary fibrosis (PF). However, at present, the mechanism and pathogenesis remain unclear. We aimed to test the hypothesis that the adenosine monophosphate-activated protein kinase (AMPK) activation and suppression of hypoxia-inducible factor 1α (HIF-1α)-induced aerobic glycolysis play a central role in septic pulmonary fibrogenesis. ⋯ In addition, pretreatment with metformin, which is an AMPK activator, suppresses HIF-1α expression and alleviates PF associated with sepsis, which is caused by aerobic glycolysis, in mice. Hypoxia-inducible factor 1α knockdown demonstrated similar protective effects in vivo. Our research implies that targeting AMPK activation and HIF-1α-induced aerobic glycolysis with metformin might be a practical and useful therapeutic alternative for sepsis-associated PF.
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Sepsis is defined as a life-threatening organ dysfunction caused by excessive host response to infection, and represents the most common cause of in-hospital deaths. Sepsis accounts for 30% of all critically ill patients in the intensive care unit (ICU), and has a global mortality rate of 20%. ⋯ Von Willebrand factor (VWF) and ADAMTS13 are two important regulators of blood coagulation that may be important links between sepsis and mortality in the ICU. Herein we review our current understanding of VWF and ADAMTS13 in sepsis and other critical illnesses and discuss their contribution to disease pathophysiology, their use as markers of severe illness, and potential targets for new therapeutic development.
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Extracellular vesicles (EVs) are a new revelation in cross-kingdom communication, with increasing evidence showing the diverse roles of bacterial EVs (BEVs) in mammalian cells and host-microbe interactions. Bacterial EVs include outer membrane vesicles released by gram-negative bacteria and membrane vesicles generated from gram-positive bacteria. Recently, BEVs have drawn attention for their potential as biomarkers and therapeutic tools because they are nano-sized and can deliver bacterial cargo into host cells. ⋯ Next, the mechanisms and pathways identified by BEVs that stimulate either proinflammatory or anti-inflammatory responses are highlighted. In addition, we discuss the mechanisms by which BEVs regulate host-microbe interactions and their effects on the immune system. Finally, this review focuses on the contribution of BEVs to the pathogenesis of sepsis/septic shock and their therapeutic potential for the treatment of sepsis.