Impact of an in-hospital endocarditis team and a state-wide endocarditis network on perioperative outcomes

Background: Infective endocarditis (IE) requires multidisciplinary management. We established an endocarditis team within our hospital in 2011 and a state-wide endocarditis network with referring hospitals in 2015. We aimed to investigate their impact on perioperative outcomes. Methods: We retrospectively analyzed data from patients operated on for IE in our center between 01/2007 and 03/2018. To investigate the impact of the endocarditis network on referral latency and pre-operative complications we divided patients into two eras: before ( n = 409) and after ( n = 221) 01/2015. To investigate the impact of the endocarditis team on post-operative outcomes we conducted multivariate binary logistic regression analyses for the whole population. Kaplan–Meier estimates of 5-year survival were reported. Results: In the second era, after establishing the endocarditis network, the median time from symptoms to referral was halved (7 days (interquartile range: 2–19) vs. 15 days (interquartile range: 6–35)), and pre-operative endocarditis-related complications were reduced, i.e., stroke (14% vs. 27%, p < 0.001), heart failure (45% vs. 69%, p < 0.001), cardiac abscesses (24% vs. 34%, p = 0.018), and acute requirement of hemodialysis (8% vs. 14%, p = 0.026). In both eras, a lack of recommendations from the endocarditis team was an independent predictor for in-hospital mortality (adjusted odds ratio: 2.12, 95% CI: 1.27–3.53, p = 0.004) and post-operative stroke (adjusted odds ratio: 2.23, 95% CI: 1.12–4.39, p = 0.02), and was associated with worse 5-year survival (59% vs. 40%, log-rank < 0.001). Conclusion: The establishment of an endocarditis network led to the earlier referral of patients with fewer pre-operative endocarditis-related complications. Adhering to endocarditis team recommendations was an independent predictor for lower post-operative stroke and in-hospital mortality, and was associated with better 5-year survival

Antiviral Interferon-Beta Signaling Induced by Designed Transcription Activator-Like Effectors (TALE)

<div><p>Here we show that designed transcription activator-like effectors (TALEs) that bind to defined areas of the interferon beta promoter are capable to induce IFN-beta expression and signaling in human cells. Importantly, TALE-mediated IFN-beta signaling occurs independently of pathogen pattern recognition but effectively prohibits viral RNA replication as demonstrated with a hepatitis C virus replicon. TALEs were thus indicated to be valuable tools in various applications addressing, for example, virus-host interactions.</p></div

TALE binding sites within the IFN-beta promoter (see also Fig. 1A).

<p>TALE binding sites within the IFN-beta promoter (see also <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0114288#pone-0114288-g001" target="_blank">Fig. 1A</a>).</p

TALE-induced expression of IFN-beta.

<p><i>(A)</i> Organization of the IFN-beta promoter (region at −134 to −13 nt upstream of transcriptional start). The nucleosome (nuc) and TALE binding sites are schematized as well as the interaction sites of transcription factors that associate with the IFN-beta promoter in activated cells forming the enhanceosome. <i>(B)</i> Expression levels of TALEs1–6 and of a control TALE (without human target sequence) in Huh7 cells, detected by western blot in comparison with the housekeeping protein Glyceraldehyde-3-Phosphate Dehydrogenase (GAPDH). <i>(C)</i> IFN-beta mRNA level in Huh7 cells at 24 h post-transfection (p.t.) of TALE-expressing plasmids (IFN-beta mRNA level in control set as 1). Error bars indicate standard deviations of seven independent experiments. (* = <i>P</i><0,05, ** = <i>P</i><0,01).</p