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
-
Observational Study
Toll like receptor 2 and 9 expression on circulating neutrophils is associated with increased mortality in critically ill patients.
Toll-like receptors (TLRs) play an important role in inflammatory processes in critically ill patients by binding to pathogen-associated molecular patterns and danger-associated molecular patterns (DAMPs). Whether neutrophil or monocyte TLR expression patterns are associated with outcome in critical illness is unknown. ⋯ We provide evidence for prognostic properties of neutrophil TLR-2 and TLR-9 expression regarding 30-day mortality in unselected critically ill patients, independent from baseline clinical characteristics, and laboratory values. These findings suggest that specific TLR-dependent activation of the innate immune system via neutrophils possibly caused by cell damage and release of otherwise intracellular components may play a significant role in the pathophysiology of critical illness.
-
Damage control laparotomy has increased survival for critically injured patient with penetrating abdominal trauma. There has been a slower adoption of a damage control strategy for thoracic trauma despite the considerable mortality associated with emergent thoracotomy for patients in profound shock. We postulated admission physiology, not blood pressure or shock index, would identify patients who would benefit from thoracic damage control. ⋯ Mortality in this series of severely injured, profoundly physiologically altered patients undergoing thoracic damage control is substantially lower than previously reported. Rather than relying on blood pressure and shock index, early recognition of shock identifies patients in whom thoracic damage control is beneficial.
-
Cardiac dysfunction, a common complication from severe sepsis, is associated with increased morbidity and mortality. However, the molecular mechanisms of septic cardiac dysfunction are poorly understood. SIRT1, a member of the sirtuin family of NAD+-dependent protein deacetylases, is an important immunometabolic regulator of sepsis, and sustained SIRT1 elevation is associated with worse outcomes and organ dysfunction in severe sepsis. Herein, we explore the role of SIRT1 in septic cardiac dysfunction using a murine model of sepsis. ⋯ Our findings reveal that SIRT1 expression increases in isolated cardiomyocytes and cardiac tissue after sepsis inflammation. Moreover, rebalancing SIRT1 excess in late sepsis improves cardiac performance, suggesting that SIRT1 may serve as a therapeutic target for septic cardiomyopathy.
-
The impact of diabetes mellitus on outcomes in trauma patients continues to attract interest, but data regarding the impact of longer term glycemic control are still lacking. This study evaluated the effect of long-term glycemic control on outcomes. Trauma patients presenting to the University of Alabama at Birmingham Hospital, between 2011 and 2018, were stratified into 4 groups, based on admission Hemoglobin A1c (HbA1c) level. ⋯ Observed associations were of similar strength for pneumonia and mortality for all less-than-excellent glycemic control groups. In conclusion, trauma patients with worse long-term glycemic control had increased risks of developing pneumonia, renal failure, urinary tract infection, and death. HbA1c can prognosticate the risks and outcomes of diabetic trauma patients.
-
In the treatment of disseminated intravascular coagulation (DIC), which is a complication of underlying diseases such as infections and malignant tumors, effective plasma concentrations of thrombomodulin (TM) alfa range from 300 to 900 ng/mL; however, appropriate concentrations when treating sepsis-induced DIC are unknown. Thus, our aim was to determine the relationship between plasma concentrations of TM alfa and its therapeutic effects, and hemorrhagic adverse events. First, we calculated the plasma trough concentrations of TM alfa in septic DIC patients. ⋯ The 90-day survival rate was significantly higher in the high-concentration group (85.4%) than in the low-concentration group (49.0%) (hazard ratio, 0.27; 95% confidence interval: 0.09-0.86). In contrast, the incidence of serious hemorrhage was not significantly different between the groups. The recommended plasma concentration of TM alfa in the treatment of septic DIC was determined to be higher than 600 ng/mL, and a dose of 380 U/kg (0.06 mg/kg) was necessary to achieve this concentration.