Silver nanoparticles impair retinoic acid-inducible gene I mediated mitochondrial anti-viral immunity by blocking the autophagic flux in lung epithelial cells

Silver nanoparticles (AgNPs) are microbicidal agents which could be potentially used as alternative to antivirals to treat human infectious diseases, especially Influenza virus infection where antivirals have generally proven unsuccessful. However, concerns about the use of AgNPs on humans arise from their potential toxicity, although mechanisms are not well-understood. We show here, in the context of Influenza virus infection of lung epithelial cells, that AgNPs down-regulated Influenza induced-CCL-5 and -IFN-β release (two cytokines important in anti-viral immunity) through RIG-I inhibition, while enhancing IL-8 production, a cytokine important for mobilizing host antibacterial responses. AgNPs activity was independent of coating and was not observed with gold nanoparticles. Down-stream analysis indicated that AgNPs disorganized the mitochondrial network and prevented the anti-viral IRF-7 transcription factor influx into the nucleus. Importantly, we showed that the modulation of RIG-I-IRF-7 pathway was concomitant with inhibition of either classical or alternative autophagy (ATG-5- and Rab-9 dependent, respectively), depending on the epithelial cell type used. Altogether, this demonstration of a AgNPs-mediated functional dichotomy (down-regulation of IFN-dependent anti-viral responses and up-regulation of IL-8 -dependent antibacterial responses) may have practical implications for their use in the clinic

Cost-effectiveness analysis of stand-alone or combined non-invasive imaging tests for the diagnosis of stable coronary artery disease: results from the EVINCI study

Aim: This study aimed at evaluating the cost-effectiveness of different non-invasive imaging-guided strategies for the diagnosis of obstructive coronary artery disease (CAD) in a European population of patients from the Evaluation of Integrated Cardiac Imaging in Ischemic Heart Disease (EVINCI) study. Methods and results: Cost-effectiveness analysis was performed in 350 patients (209 males, mean age 59 ± 9 years) with symptoms of suspected stable CAD undergoing computed tomography coronary angiography (CTCA) and at least one cardiac imaging stress-test prior to invasive coronary angiography (ICA) and in whom imaging exams were analysed at dedicated core laboratories. Stand-alone stress-tests or combined non-invasive strategies, when the first exam was uncertain, were compared. The diagnostic end-point was obstructive CAD defined as > 50% stenosis at quantitative ICA in the left main or at least one major coronary vessel. Effectiveness was defined as the percentage of correct diagnosis (cd) and costs were calculated using country-specific reimbursements. Incremental cost-effectiveness ratios (ICERs) were obtained using per-patient data and considering “no-imaging” as reference. The overall prevalence of obstructive CAD was 28%. Strategies combining CTCA followed by stress ECHO, SPECT, PET, or stress CMR followed by CTCA, were all cost-effective. ICERs values indicated cost saving from − 969€/cd for CMR-CTCA to − 1490€/cd for CTCA-PET, − 3092€/cd for CTCA-SPECT and − 3776€/cd for CTCA-ECHO. Similarly when considering early revascularization as effectiveness measure. Conclusion: In patients with suspected stable CAD and low prevalence of disease, combined non-invasive strategies with CTCA and stress-imaging are cost-effective as gatekeepers to ICA and to select candidates for early revascularization

Cost-effectiveness analysis of stand-alone or combined non-invasive imaging tests for the diagnosis of stable coronary artery disease: results from the EVINCI study

Aim: This study aimed at evaluating the cost-effectiveness of different non-invasive imaging-guided strategies for the diagnosis of obstructive coronary artery disease (CAD) in a European population of patients from the Evaluation of Integrated Cardiac Imaging in Ischemic Heart Disease (EVINCI) study.Methods and results: Cost-effectiveness analysis was performed in 350 patients (209 males, mean age 59 ± 9 years) with symptoms of suspected stable CAD undergoing computed tomography coronary angiography (CTCA) and at least one cardiac imaging stress-test prior to invasive coronary angiography (ICA) and in whom imaging exams were analysed at dedicated core laboratories. Stand-alone stress-tests or combined non-invasive strategies, when the first exam was uncertain, were compared. The diagnostic end-point was obstructive CAD defined as > 50% stenosis at quantitative ICA in the left main or at least one major coronary vessel. Effectiveness was defined as the percentage of correct diagnosis (cd) and costs were calculated using country-specific reimbursements. Incremental cost-effectiveness ratios (ICERs) were obtained using per-patient data and considering “no-imaging” as reference. The overall prevalence of obstructive CAD was 28%. Strategies combining CTCA followed by stress ECHO, SPECT, PET, or stress CMR followed by CTCA, were all cost-effective. ICERs values indicated cost saving from − 969€/cd for CMR-CTCA to − 1490€/cd for CTCA-PET, − 3,09 €/cd for CTCA-SPECT and − 3776€/cd for CTCA-ECHO. Similarly when considering early revascularization as effectiveness measure.Conclusion: In patients with suspected stable CAD and low prevalence of disease, combined non-invasive strategies with CTCA and stress-imaging are cost-effective as gatekeepers to ICA and to select candidates for early revascularization.</p

Multi-modality imaging in cardiac ATTR familial amyloidosis: agreement between echocardiography, MRI and DPD-scintigraphy

From First European Congress on Hereditary ATTR amyloidosisParis, France. 2-3 November 2015International audienceBackgroundThree main imaging techniques are commonly used to identify cardiac transthyretin (ATTR) amyloidosis: echocardiography, MRI and DPD scintigraphy. Each one provides specific diagnostic and prognostic informations but also has its specific limitations. We sought to evaluate a multimodality imaging strategy to diagnose cardiac amyloidosis in ATTR.MethodsSeventy seven consecutive patients with multimodality imaging evaluation (echocardiography, 1.5T MRI and 99mTc-DPD scintigraphy) to diagnose cardiac amyloidosis were identified from the database of the French National Reference Center for Amyloidosis. Patients with pacemaker or severe renal failure did not undergo cardiac MRI and were analyzed on the basis of the echocardiography and scintigraphy (n=17). Three groups were compared: patients with positive agreement to diagnose cardiac ATTR (PA-ATTR group), patients with positive agreement to exclude cardiac ATTR (PA-normal) and patients with negative agreement (NA).ResultsThe mean age was 52 years [44-70]; 59% were male. Transthyretin mutations were Val30Met in 67%, other in 21%, and 12% had acquired ATTR from previous domino liver transplantation; 30 patients had a positive echocardiography, 37 positive MRI and 36 positive DPD scintigraphy. Positive imaging agreement was encountered in 50/77 patients (65%: 30 PA-ATTR and 20 PA-normal). Negative agreement was observed in 27/77 patients (35%). Compared with PA-ATTR patients, NA patients were younger (68 [64-72] years vs. 46 [41-64], had lower BNP levels (149 [94-248] pg/ml vs. 40 [25-102],) and thinner interventricular septum (17 [14-20] mm vs. 12 [10-14]), all p values <0.0001). The two main causes for negative agreement between techniques was the sole positivity of the MRI (n=10) and the sole negativity of the DPD scintigraphy(n=6). Compared with PA-ATTR patients, patients with a sole MRI positivity were younger (41 [39-44] years vs. 68 [64-72] p<0.001), more frequently women (80% vs.26% p=0,002), had thinner interventricular septum (9 [8-11] mm vs.17 [14-20], p<0.0001), had lower BNP levels (26 [24-36] vs 149 [92-249] p<0.0001) and had less diffuse late gadolinium enhancement pattern (10% vs. 66% patients; p<0.0001). As compared with PA-ATTR patients, patients with a sole negativity of the DPD scintigraphy had acquired ATTR from domino liver transplantation in all but one case (83% vs. 6% patients; p=0.02).ConclusionsIn transthyretin amyloidosis, the agreement between echocardiography, cardiac MRI and DPD scintigraphy to diagnose cardiac amyloidosis was observed in 65% of patients. Patients without agreement between these three techniques had distinct patterns of cardiac involvement: sole positivity of the MRI was encountered in patients in the early stages of ATTR; patients with acquired ATTR due to domino liver transplantation often had negative DPD scintigraphy