Critical care : the official journal of the Critical Care Forum
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Comparative Study
PD-L1 blockade improves survival in experimental sepsis by inhibiting lymphocyte apoptosis and reversing monocyte dysfunction.
Lymphocyte apoptosis and monocyte dysfunction play a pivotal role in sepsis-induced immunosuppression. Programmed death-1 (PD1) and its ligand programmed death ligand-1 (PD-L1) exert inhibitory function by regulating the balance among T cell activation, tolerance, and immunopathology. PD-1 deficiency or blockade has been shown to improve survival in murine sepsis. However, PD-L1 and PD-1 differ in their expression patterns and the role of PD-L1 in sepsis-induced immunosuppression is still unknown. ⋯ PD-L1 blockade exerts a protective effect on sepsis at least partly by inhibiting lymphocyte apoptosis and reversing monocyte dysfunction. Anti-PD-L1 antibody administration may be a promising therapeutic strategy for sepsis-induced immunosuppression.
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During the past decade, there have been an increasing number of studies investigating the precise role of T regulatory cells in human disease. First recognized for their ability to prevent autoimmunity, T regulatory cells control effector CD4+ and CD8+ T lymphocytes and innate immune cells by several different suppressive mechanisms, like cell to cell contact, secretion of inhibitory cytokines and cytolysis. This suppressive function of T regulatory cells could contribute in a similar way to the profound immune dysfunction seen in critical illness whether the latter is due to sepsis or severe injury.
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Comment Letter
Increased blood flow by insulin infusion targeting normoglycemia in patients with severe sepsis: friend or foe?
A small study in patients with severe sepsis suggested that insulin infused to normalize blood glucose levels increased forearm flow. This clinical observation supports the effect of insulin on the endothelium, as previously shown by in vitro studies and by in vivo animal models of critical illness, but the clinical consequences remain unclear.
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Goal-directed therapy (GDT) can be a vague term, meaning different things to different people and, depending on the clinical environment, sometimes even different things to the same person. It can refer to perioperative fluid management, clinicians driving oxygen delivery to supramaximal values, early treatment of sepsis in the emergency department, and even to restriction of perioperative crystalloids with the goal of maintaining preadmission body weight. Understandably, strong opinions about GDT vary; some clinicians consider it essential for perioperative care, others completely ineffective in critically ill patients. This commentary aims to further position the excellent review by Lees and colleagues in the context of the critical care and perioperative setting.
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We found that pulse pressure variation (PPV) did not predict volume responsiveness in patients with increased pulmonary artery pressure. This study tests the hypothesis that PPV does not predict fluid responsiveness during an endotoxin-induced acute increase in pulmonary artery pressure and right ventricular loading. ⋯ Fluid responsiveness cannot be predicted with PPV during acute pulmonary hypertension in porcine endotoxemia. Even following severe hemorrhage during endotoxemia, the predictive value of PPV is marginal.