Critical care : the official journal of the Critical Care Forum
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The TraumaRegister DGU™ (TR-DGU) has used the Revised Injury Severity Classification (RISC) score for outcome adjustment since 2003. In recent years, however, the observed mortality rate has fallen to about 2% below the prognosis, and it was felt that further prognostic factors, like pupil size and reaction, should be included as well. Finally, an increasing number of cases did not receive a RISC prognosis due to the missing values. Therefore, there was a need for an updated model for risk of death prediction in severely injured patients to be developed and validated using the most recent data. ⋯ The updated RISC II prognostic score has several advantages over the previous RISC model. Discrimination, precision and calibration are improved, and patients with partial missing values could now be included. Results were confirmed in a validation dataset.
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Sepsis and other infections are associated with late cardiovascular events. Although persistent inflammation is implicated, a causal relationship has not been established. We tested whether sepsis causes vascular inflammation and accelerates atherosclerosis. ⋯ Using a combination of existing murine models for atherosclerosis and sepsis, we found that CLP, a model of intra-abdominal sepsis, accelerates atheroma development. Accelerated atheroma burden was associated with prolonged systemic, endothelial and intimal inflammation and was not explained by ongoing infection. These findings support observations in humans and demonstrate the feasibility of a long-term follow-up murine model of sepsis.
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Acute kidney injury (AKI) is a common and feared complication of sepsis. The pathogenesis of sepsis-induced AKI is largely unknown, and therapeutic interventions are mainly supportive. In the present study, we tested the hypothesis that pharmacological inhibition of Toll-like receptor 4 (TLR4) would improve renal function and reduce renal damage in experimental sepsis, even after AKI had already developed. ⋯ These results show that treatment with a TLR4 inhibitor is able to reverse a manifest impairment in renal function caused by sepsis. In addition, the results provide evidence that the mechanism underlying the effect of TAK-242 on renal function does not involve improved macro-circulation or micro-circulation, enhanced renal oxygen delivery, or attenuation of tubular necrosis. TLR4-mediated inflammation resulting in glomerular endothelial swelling may be an important part of the pathogenesis underlying Gram-negative septic acute kidney injury.
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The most common cause of acute kidney injury (AKI) in hospitalized patients is sepsis. However, the molecular pathways and mechanisms that mediate septic AKI are not well defined. Experiments performed over the past 20 years suggest that there are profound differences in the pathogenesis between septic and ischemic AKI. ⋯ This failure is likely due to the protean nature of septic AKI, whereby different patients present at different points along the immunologic spectrum. While one patient may benefit from targeted therapy at one end of the spectrum, another patient at the other end may be harmed by the same therapy. We propose that a next important step in septic AKI research will be to identify where patients lie on the immunologic spectrum in order to appropriately target therapies at the inflammatory cascade, TLRs, and possibly apoptosis.