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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Observational Study
Predictive Factors of Duration of Continuous Renal Replacement Therapy in Acute Kidney Injury Survivors.
The factors influencing continuous renal replacement therapy (CRRT) duration for critically ill patients with acute kidney injury (AKI) are unclear. Therefore, we investigated the clinical factors that could influence the duration of CRRT for AKI survivors. In this retrospective observational study, the medical records of all hospital survivors who required CRRT for AKI in intensive care units were analyzed. ⋯ A clinical model demonstrated a good discriminatory ability to predict long-duration CRRT (area under the curve, 0.84; 95% confidence interval, 0.76-0.90). The urine output immediately before CRRT initiation and factors associated with disease severity significantly affected the duration of CRRT. Simultaneously considering the urine output, mechanical ventilation use, and ECMO use predicted CRRT duration in AKI survivors.
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Significant impairments in mitochondrial function are associated with the development of multi-organ failure in sepsis/endotoxaemia, but the data on the dynamics of simultaneous mitochondrial impairment in multiple organs are limited. The aim of this study was to evaluate the changes in heart, brain and kidney mitochondrial function in an experimental model of lipopolysaccharide (LPS)-induced endotoxaemia. Samples were collected 4 and 24 h after single injection of LPS (10 mg/kg) in mice. ⋯ The brain mitochondria demonstrated a slightly impaired mitochondrial functionality just 24 h after the induction of endotoxaemia. In conclusion, among studied tissues kidney mitochondria are the most sensitive to endotoxaemia and do not recover from LPS-induced damage, whereas in brain, mitochondrial function was not significantly altered. In heart, endotoxaemia induces a decrease in the mitochondrial fatty acid oxidation capacity, but during the phase of suppressed inflammatory response, the ET efficiency is improved despite the marked increase in reactive oxygen species production.
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Vitamin D deficiency is related to various cardiovascular diseases, including sudden cardiac arrest (SCA). This study investigated the association of vitamin D level with neurologic outcome and mortality after resuscitation from SCA. ⋯ Vitamin D deficiency is very prevalent and strongly associated with both unfavorable neurologic outcome and mortality in patients resuscitated from SCA.
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The clinical use of gentamicin over prolonged periods is limited because of dose and time-dependent nephrotoxicity, in which intracellular oxidative stress and heightened inflammation have been implicated. Macroautophagy/autophagy is an essential and highly conserved self-digestion pathway that plays important roles in the maintenance of cellular function and viability under stress. The aim of this study was to determine changes in autophagy in response to the antioxidant N-acetylcysteine (NAC), via its effects on oxidative stress, inflammation, apoptosis, and renal function, following treatment with gentamicin in mini pigs. ⋯ NAC also caused a significant reduction in oxidative damage markers, including 4-hydroxy-2-nonenal, protein carbonyls, γ-H2AX (gamma histone variant H2AX), and 8-hydroxy-2'-deoxyguanosine, in gentamicin-treated animals. These data show that the protective effects of NAC might be related, at least in part, to a reduced inflammatory response, as observed in animals treated with both gentamicin and NAC. These results suggest that autophagy could be a new therapeutic target for preventing gentamicin-induced kidney injury, and that NAC might ameliorate gentamicin-induced nephrotoxicity by autophagy.
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Lipopolysaccharide Stress Induces Cryptic Exon Splice Variants of the Human Glucocorticoid Receptor.
Glucocorticoids are widely used in the treatment of numerous inflammatory conditions, including sepsis. Unfortunately, patient response to glucocorticoid therapy can be inconsistent. Variations in the human glucocorticoid receptor (hGR) may contribute to the differential patient response. ⋯ This shows that PBMCs are able to produce variant hGR isoforms in response to stress. Furthermore, lipopolysaccharide stress appears to induce these hGR variants, potentially by influencing mRNA splicing. In the future, identifying hGR expression profiles may be a key component in individually tailoring a patient's treatment to sepsis and injury.