European journal of clinical investigation
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Eur. J. Clin. Invest. · Dec 2018
ReviewC5a anaphylatoxin and its role in critical illness-induced organ dysfunction.
Critical illness is an aetiologically and clinically heterogeneous syndrome that is characterised by organ failure and immune dysfunction. Mortality in critically ill patients is driven by inflammation-associated organ damage and a profound vulnerability to nosocomial infection. Both factors are influenced by the activated complement protein C5a, released by unbridled activation of the complement system during critical illness. ⋯ Whilst several recent reports have added key knowledge of the cellular signalling pathways triggered by C5a, there remain a number of areas that are incompletely understood and therapeutic opportunities are still being evaluated. In this review, we summarise the cellular basis for C5a-induced vulnerability to nosocomial infection and organ dysfunction. We focus on cells of the innate immune system, highlighting the major areas in need of further research and potential avenues for targeted therapies.
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Eur. J. Clin. Invest. · Dec 2018
Comparative Study Observational StudyAge-dependent effect of targeted temperature management on outcome after cardiac arrest.
In elder patients after out-of-hospital cardiac arrest, diminished neurologic function as well as reduced neuronal plasticity may cause a low response to targeted temperature management (TTM). Therefore, we investigated the association between TTM (32-34°C) and neurologic outcome in cardiac arrest survivors with respect to age. ⋯ In our cohort, it seems that TTM might not be able to achieve the same benefit for neurologic outcome in all age groups. Although the results of this study should be interpreted with caution, TTM was associated with improved neurologic outcome only in younger individuals, patients with 65 years of age or older did not benefit from this treatment.
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Eur. J. Clin. Invest. · Dec 2018
Variants in cardiac GATA genes associated with bicuspid aortic valve.
Bicuspid aortic valve (BAV) is a heterogeneous and still not fully understood condition, with diverse genetic aetiology and associated phenotypes ranging from aortic stenosis or regurgitation to aneurysm and dissection. Several genes have been associated with the presence of BAV, notably some members of the GATA family of transcription factors that play important roles in cardiac embryogenesis. ⋯ This study associates additional genetic variants in GATA4 and GATA5 with BAV, supporting the implication of these genes in the development of this valvulopathy. The discovery of all the genetic factors involved will contribute to a better understanding of the process and, therefore, to detect a genetic predisposition and even to the identification of therapeutic targets.