Head-to-head comparison of two angiography-derived fractional flow reserve techniques in patients with high-risk acute coronary syndrome: A multicenter prospective study.

FFRangio and QFR are angiography-based technologies that have been validated in patients with stable coronary artery disease. No head-to-head comparison to invasive fractional flow reserve (FFR) has been reported to date in patients with acute coronary syndromes (ACS). This study is a subset of a larger prospective multicenter, single-arm study that involved patients diagnosed with high-risk ACS in whom 30-70% stenosis was evaluated by FFR. FFRangio and QFR - both calculated offline by 2 different and blinded operators - were calculated and compared to FFR. The two co-primary endpoints were the comparison of the Pearson correlation coefficient between FFRangio and QFR with FFR and the comparison of their inter-observer variability. Among 134 high-risk ACS screened patients, 59 patients with 84 vessels underwent FFR measurements and were included in this study. The mean FFR value was 0.82 ± 0.40 with 32 (38%) being ≤0.80. The mean FFRangio was 0.82 ± 0.20 and the mean QFR was 0.82 ± 0.30, with 27 (32%) and 25 (29%) being ≤0.80, respectively. The Pearson correlation coefficient was significantly better for FFRangio compared to QFR, with R values of 0.76 and 0.61, respectively (p = 0.01). The inter-observer agreement was also significantly better for FFRangio compared to QFR (0.86 vs 0.79, p < 0.05). FFRangio had 91% sensitivity, 100% specificity, and 96.8% accuracy, while QFR exhibited 86.4% sensitivity, 98.4% specificity, and 93.7% accuracy. In patients with high-risk ACS, FFRangio and QFR demonstrated excellent diagnostic performance. FFRangio seems to have better correlation to invasive FFR compared to QFR but further larger validation studies are required

Under-reporting bicycle accidents to police in the COST TU1101 international survey: Cross-country comparisons and associated factors

Police crash reports are often the main source for official data in many countries. However, with the exception of fatal crashes, crashes are often underreported in a biased manner. Consequently, the countermeasures adopted according to them may be inefficient. In the case of bicycle crashes, this bias is most acute and it probably varies across countries, with some of them being more prone to reporting accidents to police than others. Assessing if this bias occurs and the size of it can be of great importance for evaluating the risks associated with bicycling. This study utilized data collected in the COST TU1101 action “Towards safer bicycling through optimization of bicycle helmets and usage”. The data came from an online survey that included questions related to bicyclists' attitudes, behaviour, cycling habits, accidents, and patterns of use of helmets. The survey was filled by 8655 bicyclists from 30 different countries. After applying various exclusion factors, 7015 questionnaires filled by adult cyclists from 17 countries, each with at least 100 valid responses, remained in our sample. The results showed that across all countries, an average of only 10% of all crashes were reported to the police, with a wide range among countries: from a minimum of 0.0% (Israel) and 2.6% (Croatia) to a maximum of a 35.0% (Germany). Some factors associated with the reporting levels were type of crash, type of vehicle involved, and injury severity. No relation was found between the likelihood of reporting and the cyclist's gender, age, educational level, marital status, being a parent, use of helmet, and type of bicycle. The significant under-reporting – including injury crashes that do not lead to hospitalization – justifies the use of self-report survey data for assessment of bicycling crash patterns as they relate to (1) crash risk issues such as location, infrastructure, cyclists' characteristics, and use of helmet and (2) strategic approaches to bicycle crash prevention and injury reduction.Fil: Shinar, D.. Ben Gurion University of the Negev; IsraelFil: Valero Mora, Pedro. Universidad de Valencia; EspañaFil: van Strijp Houtenbos, M.. Institute For Road Safety Research; Países BajosFil: Haworth, N.. Queensland University of Technology; AustraliaFil: Schramm, A.. Queensland University of Technology; AustraliaFil: de Bruyne, G.. Universiteit Antwerp; BélgicaFil: Cavallo, V.. No especifíca;Fil: Chliaoutakis, J.. No especifíca;Fil: Pereira Dias, Joao. Instituto Superior Tecnico; PortugalFil: Ferraro, Ottavia Eleonora. Universita Degli Studi Di Pavia; ItaliaFil: Fyhri, Aslak. No especifíca;Fil: Sajatovic, Anika Hursa. No especifíca;Fil: Kuklane, Kalev. Lund University; SueciaFil: Ledesma, Ruben Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Psicología Básica, Aplicada y Tecnología. Universidad Nacional de Mar del Plata. Facultad de Psicología. Instituto de Psicología Básica, Aplicada y Tecnología.; ArgentinaFil: Calvé Mascarell, Oscar. Ben Gurion University of the Negev; IsraelFil: Morandi, A.. Universita Degli Studi Di Pavia; ItaliaFil: Muser, Markus. No especifíca;Fil: Otte, Diettmar. No especifíca;Fil: Papadakaki, M.. No especifíca;Fil: Sanmartín, J.. Universidad de Valencia; EspañaFil: Dulf, D.. No especifíca;Fil: Saplioglu, M.. No especifíca;Fil: Tzamalouka, Georgia. No especifíca

Insulin-like growth factor I activates the invasion suppressor function of E-cadherin in MCF-7 human mammary carcinoma cells in vitro.

The calcium-dependent cell-cell adhesion molecule E-cadherin has been shown to counteract invasion of epithelial neoplastic cells. Using three monoclonal antibodies, we have demonstrated the presence of E-cadherin at the surface of human MCF-7/6 mammary carcinoma cells by indirect immunofluorescence coupled to flow cytometry and by immunocytochemistry. Nevertheless, MCF-7/6 cells failed to aggregate in a medium containing 1.25 mM CaCl2, and they were invasive after confrontation with embryonic chick heart fragments in organ culture. Treatment of MCF-7/6 cells with 0.5 microgram ml-1 insulin-like growth factor I (IGF-I) led to homotypic aggregation within 5 to 10 min and inhibited invasion in vitro during at least 8 days. The effect of IGF-I on cellular aggregation was insensitive to cycloheximide. However, monoclonal antibodies that interfered with the function of either the IGF-I receptor (alpha IR3) or E-cadherin (HECD-1, MB2) blocked the effect of IGF-I on aggregation. The effects of IGF-I on aggregation and on invasion could be mimicked by 1 microgram ml-1 insulin, but not by 0.5 microgram ml-1 IGF-II. The insulin effects were presumably not mediated by the IGF-I receptor, since they could not be blocked by an antibody against this receptor (alpha IR3). Our results indicate that IGF-I activates the invasion suppressor role of E-cadherin in MCF-7/6 cells

The Disrupt CAD II Study

BACKGROUND: The feasibility of intravascular lithotripsy (IVL) for modification of severe coronary artery calcification (CAC) was demonstrated in the Disrupt CAD I study (Disrupt Coronary Artery Disease). We next sought to confirm the safety and effectiveness of IVL for these lesions. METHODS: The Disrupt CAD II study was a prospective multicenter, single-arm post-approval study conducted at 15 hospitals in 9 countries. Patients with severe CAC with a clinical indication for revascularization underwent vessel preparation for stent implantation with IVL. The primary end point was in-hospital major adverse cardiac events (cardiac death, myocardial infarction, or target vessel revascularization). An optical coherence tomography substudy was performed to evaluate the mechanism of action of IVL, quantifying CAC characteristics and calcium plaque fracture. Independent core laboratories adjudicated angiography and optical coherence tomography, and an independent clinical events committee adjudicated major adverse cardiac events. RESULTS: Between May 2018 and March 2019, 120 patients were enrolled. Severe CAC was present in 94.2% of lesions. Successful delivery and use of the IVL catheter was achieved in all patients. The post-IVL angiographic acute luminal gain was 0.83±0.47 mm, and residual stenosis was 32.7±10.4%, which further decreased to 7.8±7.1% after drug-eluting stent implantation. The primary end point occurred in 5.8% of patients, consisting of 7 non-Q-wave myocardial infarctions. There was no procedural abrupt closure, slow or no reflow, or perforations. In 47 patients with post-percutaneous coronary intervention optical coherence tomography, calcium fracture was identified in 78.7% of lesions with 3.4±2.6 fractures per lesion, measuring 5.5±5.0 mm in length. CONCLUSIONS: In patients with severe CAC who require coronary revascularization, IVL was safely performed with high procedural success and minimal complications and resulted in substantial calcific plaque fracture in most lesions. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03328949

Fractional flow reserve versus angiography for guidance of PCI in patients with multivessel coronary artery disease (FAME): 5-year follow-up of a randomised controlled trial

In the Fractional Flow Reserve Versus Angiography for Multivessel Evaluation (FAME) study, fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) improved outcome compared with angiography-guided PCI for up to 2 years of follow-up. The aim in this study was to investigate whether the favourable clinical outcome with the FFR-guided PCI in the FAME study persisted over a 5-year follow-up

Tasquinimod suppresses tumor cell growth and bone resorption by targeting immunosuppressive myeloid cells and inhibiting c-MYC expression in multiple myeloma

Background: Immunotherapy emerged as a promising treatment option for multiple myeloma (MM) patients. However, therapeutic efficacy can be hampered by the presence of an immunosuppressive bone marrow microenvironment including myeloid cells. S100A9 was previously identified as a key regulator of myeloid cell accumulation and suppressive activity. Tasquinimod, a small molecule inhibitor of S100A9, is currently in a phase Ib/IIa clinical trial in MM patients (NCT04405167). We aimed to gain more insights into its mechanisms of action both on the myeloma cells and the immune microenvironment. Methods: We analyzed the effects of tasquinimod on MM cell viability, cell proliferation and downstream signaling pathways in vitro using RNA sequencing, real-time PCR, western blot analysis and multiparameter flow cytometry. Myeloid cells and T cells were cocultured at different ratios to assess tasquinimod-mediated immunomodulatory effects. The in vivo impact on immune cells (myeloid cell subsets, macrophages, dendritic cells), tumor load, survival and bone disease were elucidated using immunocompetent 5TMM models. Results: Tasquinimod treatment significantly decreased myeloma cell proliferation and colony formation in vitro, associated with an inhibition of c-MYC and increased p27 expression. Tasquinimod-mediated targeting of the myeloid cell population resulted in increased T cell proliferation and functionality in vitro. Notably, short-term tasquinimod therapy of 5TMM mice significantly increased the total CD11b+ cells and shifted this population toward a more immunostimulatory state, which resulted in less myeloid-mediated immunosuppression and increased T cell activation ex vivo. Tasquinimod significantly reduced the tumor load and increased the trabecular bone volume, which resulted in prolonged overall survival of MM-bearing mice in vivo. Conclusion: Our study provides novel insights in the dual therapeutic effects of the immunomodulator tasquinimod and fosters its evaluation in combination therapy trials for MM patients