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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Clinical Trial Observational Study
Mechanisms of Thrombocytopenia During Septic Shock: A Multiplex Cluster Analysis of Endogenous Sepsis Mediators.
Thrombocytopenia is a common feature of sepsis and may involve various mechanisms often related to the inflammatory response. This study aimed at evaluating factors associated with thrombocytopenia during human septic shock. In particular, we used a multiplex analysis to assess the role of endogenous sepsis mediators. ⋯ Multiple mechanisms seemed involved in thrombocytopenia during septic shock, including endothelial dysfunction/coagulopathy, hemodilution, and altered thrombopoiesis.
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No pharmacological interventions are currently available to provide neuroprotection for patients suffering from cardiac arrest. Dichloroacetate (DCA) is a pyruvate dehydrogenase kinase inhibitor, which activates pyruvate dehydrogenase (PDH), and increases cell adenosine triphosphate (ATP) production by promoting influx of pyruvate into the Krebs cycle. In this study, we investigated the effects of DCA on post-resuscitation neurological injury in an asphyxial cardiac arrest rat model. ⋯ In addition, DCA reduced the messenger RNA expression of tumor necrosis factor α and interleukin 1β in brain hippocampus and cortex after ROSC. Furthermore, DCA treatment significantly increased ATP production, PDH activity, and decreased blood glucose, lactate, and brain pyruvate levels after ROSC. Our results suggested that DCA has neuroprotective effects on brain injury after cardiac arrest, and its salutary effects were associated with an increase of mitochondrial energy metabolism in the brain through activation of PDH activity.
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Sepsis is a systemic inflammatory response as a result of uncontrolled infections. Neutrophils are the first cells to reach the primary sites of infection, and chemokines play a key role in recruiting neutrophils. However, in sepsis chemokines could also contribute to neutrophil infiltration to vital organs leading to multiple organ failure. ⋯ Consistent with these results, WT mice under nonsevere sepsis (90% survival) had higher expression of ACKR2 in these organs than mice under severe sepsis (no survival). Finally, the lungs from septic patients showed increased number of ACKR2 cells compared with those of nonseptic patients. Our data indicate that ACKR2 may have a protective role during sepsis, and the absence of ACKR2 leads to exacerbated chemokine accumulation, neutrophil infiltration, and damage to vital organs.
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Comparative Study Clinical Trial Observational Study
Expression and Clinical Correlations of Co-Stimulatory Molecules on Peripheral T Lymphocyte Subsets of Early-Stage Severe Sepsis: A Prospective Observational Study.
The aim of the study was to investigate the expression and clinical correlations of costimulatory molecules on peripheral T-cell subsets of severe sepsis (SS) patients. ⋯ Early-stage SS patients exhibited an activated T-cell phenotype. Imbalanced OX40 and 4-1BB expression presented on Tregs and Tconvs may contribute to a functional imbalance of Tregs/Tconvs. The frequency of CD4+CD27+ T cells and OX40+ on CD4+CD27-CD28- T cells predicted 28-day mortality of SS.
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Clinical Trial Observational Study
Associations of Plasma Nitrite, L-Arginine and Asymmetric Dimethylarginine with Morbidity and Mortality in Patients with Necrotizing Soft Tissue Infections.
The nitric oxide system could play an important role in the pathophysiology related to necrotizing soft tissue infection (NSTI). Accordingly, we investigated the association between plasma nitrite level at admission and the presence of septic shock in patients with NSTI. We also evaluated the association between nitrite, asymmetric dimethylarginine (ADMA), L-arginine, L-arginine/ADMA ratio, and outcome. ⋯ In patients with NSTI, we found no difference in baseline nitrite levels according to septic shock. High baseline ADMA level was associated with the use of RRT and patients with a low baseline L-arginine/ADMA ratio were at higher risk of dying within 28 days after hospital admission.