Critical care : the official journal of the Critical Care Forum
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Review
Bench-to-bedside review: endotoxin tolerance as a model of leukocyte reprogramming in sepsis.
Endotoxin tolerance is defined as a reduced responsiveness to a lipopolysaccharide (LPS) challenge following a first encounter with endotoxin. Endotoxin tolerance protects against a lethal challenge of LPS and prevents infection and ischemia-reperfusion damage. Endotoxin tolerance is paralleled by a dramatic reduction of tumor necrosis factor (TNF) production and some other cytokines in response to LPS. ⋯ Studies on cellular signaling within leukocytes from septic and SIRS patients reveal numerous alterations reminiscent of those observed in endotoxin tolerant cells. However, altered responsiveness to LPS of leukocytes from sepsis and SIRS patients is not synonymous with a global down-regulation of cellular reactivity. The term 'cellular reprogramming', which has been proposed to qualify the process of endotoxin tolerance, defines well the immune status of circulating leukocytes in septic and SIRS patients.
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Donation after circulatory death (DCD) can be performed on neurologically intact donors who do not fulfill neurologic or brain death criteria before circulatory arrest. This commentary focuses on the most controversial donor-related issues anticipated from mandatory implementation of DCD for imminent or cardiac death in hospitals across the USA. We conducted a nonstructured review of selected publications and websites for data extraction and synthesis. ⋯ Legislative abandonment of the dead donor rule to permit the recovery of transplantable organs is necessary in the absence of an adequate scientific foundation for DCD practice. The designation of organ procurement organizations or affiliates to obtain organ donation consent introduces self-serving bias and conflicts of interest that interfere with true informed consent. It is important that donors and their families are not denied a 'good death', and the impact of DCD on quality of end-of-life care has not been satisfactorily addressed to achieve this.
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Cognitive dysfunction is common in critically ill patients, not only during the acute illness but also long after its resolution. A large number of pathophysiologic mechanisms are thought to underlie critical illness-associated cognitive dysfunction, including neuro-transmitter abnormalities and occult diffuse brain injury. ⋯ Although recent therapeutic advances in this area are exciting, they are still too immature to influence patient care. Additional research is needed if we are to understand better the relative contributions of specific mechanisms to the development of critical illness-associated cognitive dysfunction and to determine whether these mechanisms might be amenable to treatment or prevention.
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Comparative Study
Decreases in procalcitonin and C-reactive protein are strong predictors of survival in ventilator-associated pneumonia.
This study sought to assess the prognostic value of the kinetics of procalcitonin (PCT), C-reactive protein (CRP) and clinical scores (clinical pulmonary infection score (CPIS), Sequential Organ Failure Assessment (SOFA)) in the outcome of ventilator-associated pneumonia (VAP) at an early time point, when adequacy of antimicrobial treatment is evaluated. ⋯ Measurement of PCT and CRP at onset and on the fourth day of treatment can predict survival of VAP patients. A decrease in either one of these marker values predicts survival.
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Review Historical Article
Bench-to-bedside review: human subjects research--are more standards needed?
There are many controversial issues surrounding ethics in study design and conduct of human subjects research. In this review we briefly touch on the origin of ethics in clinical research and how the current regulations and standards came into practice. ⋯ We address this question by reviewing and commenting on relevant literature. We conclude that what is needed are not more standards per se, but rather refinement and uniformity of current standards, and their interpretation and application both to protect human subjects and to advance medicine.