Critical care : the official journal of the Critical Care Forum
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Sepsis leads to microcirculatory dysfunction and therefore a disturbed neurovascular coupling in the brain. To investigate if the dysfunction is also present in less severe inflammatory diseases we studied the neurovascular coupling in patients suffering from community acquired pneumonia. ⋯ Our study underlines the role of an early microcirculatory dysfunction in inflammatory syndromes that become evident in pre-septic conditions with a gradual decline according to disease severity.
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Fever is considered a key actor of innate immunity aimed to fight infection. A new investigation reports an association of the use of antipyretic drugs with poorer outcome among patients with sepsis. In contrast, high temperature in non-infectious intensive care patients is associated with higher mortality.
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Cannabinoid receptor 2 (CB2R) expression is upregulated during sepsis. However, there are conflicting results regarding the effects of CB2R modulation in the hyperinflammatory phase of the disease. The aim of this study was therefore to investigate the effects of CB2R manipulation on leukocyte activation within the intestinal microcirculation in two acute experimental sepsis models. ⋯ CB2R activation reduces leukocyte activation and systemic release of inflammatory mediators in acute experimental sepsis. Drugs targeting the CB2R pathway may have therapeutic potential in sepsis.
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Blockade of the CXC chemokine receptor 3 (CXCR3) attenuates inflammation and improves survival in a murine model of near lethal polymicrobial sepsis. However, given the multitude of cellular responses and inflammatory mediators that orchestrate sepsis syndrome, more detailed investigations will be required before a complete understanding of the mechanism(s) of CXCR3 blockade and its therapeutic potential are revealed.
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There is a plethora of experimental data on the potential therapeutic benefits of recombinant human erythropoietin (rhEPO) and its synthetic derivatives in critical care medicine, in particular in ischemia/reperfusion injury. Most of the recent clinical trials have not shown clear benefits, and, in some patients, EPO-aggravated morbidity and mortality was even reported. Treatment with rhEPO has been successfully used in patients with anemia resulting from chronic kidney disease, but even a subset of this patient population does not adequately respond to rhEPO therapy. The following viewpoint uses rhEPO as an example to highlight the possible pitfalls in current practice using young healthy animals for the evaluation of therapies to treat patients of variable age and underlying chronic co-morbidity.