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Von Willebrand disease is a commonly inherited bleeding disorder caused by defects of von Willebrand factor (vWF). In the most common valve diseases, aortic valve stenosis (AVS) and mitral valve regurgitation (MVR), a bleeding tendency has been described in a number of patients. This has been associated to a high turbulence of blood flow through the compromised valve, promoting degradation of vWF with loss of high-molecular-weight multimers of vWF (HMWM), leading to an acquired von Willebrand syndrome (AvWS). We analysed three groups of patients, one affected by AVS, treated with transcatheter aortic valve implantation (TAVI), the second group of patients affected by MVR, treated with Mitraclip® mitral valve repair. The third group was represented by patients also affected by AVS, but not eligible for TAVI and treated with standard surgery. A fourth group of patients that underwent percutaneous coronary intervention (PCI) with stenting was used as a control. Our results demonstrated that the level of vWF measured as antigen concentration (vWF:Ag) increases in all cohorts of patients after treatment, while in control PCI patients, no modification of vWF:Ag has been registered. Western blot analysis showed only a quantitative loss of vWF in the pre-treatment time, but without significant HMWM modification. The monitoring of the vWF:Ag concentration, but not the quality of HMWM, can indicate the status of blood flow in the treated patients, thus introducing the possibility of using the vWF antigen detection in monitoring the status of replaced or repaired valves.

Background PLATO study showed that Ticagrelor (Ti) significantly reduced the rate of death from vascular causes, myocardial infarction or stroke without a significant increase of major bleeding vs Clopidogrel (Cl). Previous studies demonstrated the stronger direct anti-platelet effect of Ti versus Cl. Few data exist about the indirect anti-platelet properties and pleiotropic effects, eventually involved in the positive effect of Ti on acute coronary syndrome (ACS) outcome. Aim As Ti has multiple pleiotropic effects, we sought to assess whether the different outcome of Ti versus Cl in NSTE-ACS patients could be explained, at least in part, by different modulation of circulating microRNA (miRNA). The primary endpoint was to characterize the effect of the two different P2Y12 inhibitors on miRNA expression. Secondary endpoint was to correlate miRNA profile to clinical outcome. Methods Thirty-one patients with a diagnosis of NSTE-ACS were enrolled in this study. Patients were randomized for Ti or Cl assumption before undergoing PCI. Clinical characteristics were homologues between Ti and Cl groups. Blood samples were drawn at different time point (T0, T1 and T2) to test miRNA modulation and stability (T0, at baseline; T1, three hours after drug administration; T2, twenty-four hours after coronarography). Plasma RNA was extracted and pooled for microarray PCR based panel of ninety miRNA analysis. MiRNA expression was normalized on the global mean of each patient. Levels of circulating miRNAs were compared using statistical tests, assuming significance at P Results A panel of seven circulating miRNAs associated with atherosclerosis, thrombosis and inflammation were selected for validation (miR-652-3p; miR-26-5p; miR-25-3p; miR-let7c; miR-155-5p; miR-222-3p; miR-223-3p). Microarray analysis showed an opposite modulation of most miRNAs at T0, T1 and T2 in patients with Cl or Ti treatment. In particular, Cl group showed an upregulation of most miRNAs, while Ti administration caused their down-regulation. Of the seven miRNA selected for validation, miR-652-3p, expression at T1 showed a significantly modulation in patients in Cl treatment compared to Ti (T1 Cl 2,637±1,092, T1 Ti 0,660±0,171; p=0.03). MiRNA-652-3p has a validated pro-atherogenic role. On five-years follow, an higher rate (40%) of cardiovascular events (new ACS, recurrent ischemia and stent thrombosis) was reported in the Cl group compare to Ti. Indeed, no one death or bleeding occurred. Conclusion This data suggest that Ti has a protective role down-regulating pro-atherogenic and pro-thrombotic miRNAs (miR-652-3p, miR-let7c, miR-223-3p, miR-155-5p) and promoting the expression of anti-atherogenic miRNAs (miR-25-3p) when compared to Cl. This may contribute to explain the positive effect on clinical outcome of Ti. Although the small number of patients, this pilot study gives another evidence about the multiple positive pleiotropic effect of Ti. Figure 1. miRNA 652-3p expression Funding Acknowledgement Type of funding source: None

BACKGROUND: Perilipin 2 (PLIN2) is a protein that potentially facilitates atherogenesis in native coronary arteries or arteries with an implanted drug-eluting stent (DES). The aim of the study was to determine PLIN2 protein levels in peripheral monocytes of enrolled subjects and compare them between patients with native coronary artery disease (CAD) and those with an in-stent restenosis (ISR) due to neoatherosclerosis occurring >1 year after DES implantation. METHODS: Forty-two patients were prospectively enrolled in the study in 3:1 fashion and underwent coronary catheterization. Both groups were angiographically matched for CAD burden with respect to the number of diseased vessels. Neoatherosclerosis was determined by intracoronary optical coherence tomography (OCT) among patients with ISR. RESULTS: Patients with ISR due to neoatherosclerosis had significantly higher PLIN2 protein levels in peripheral blood monocytes compared to patients with native CAD (342.47 ± 75.63[SE] versus 119.51 ± 20.95, p < 0.001). PLIN2 protein levels did not significantly differ between unstable and stable disease phenotype (125.59 ± 131.02 vs. 146.14 ± 111.87, p = 0.109). CONCLUSIONS: In this explorative study, PLIN2 protein levels are significantly increased in patients with neoatherosclerosis, irrespective of clinical presentation, implicating that it might play a pathogenetic role in accelerated atherosclerosis after DES implantation. Further larger clinical studies are warranted to confirm these initial findings.

BACKGROUND Multidrug resistance protein-4 (MRP4) is an ATP binding cassette membrane transporter, actively involved in the efflux of important pharmacological and physiological molecules. Recently, its over-expression has been associated with reduced aspirin (ASA) efficacy after by-pass surgery. MicroRNAs (miRNAs) are small molecules of non-coding RNA involved in the regulation of many physiological and pathophysiological pathways, are abundant in platelets, and can be modulated by several drugs. In the present study, we assessed the role of platelet miRNAs in modulating MRP4 function in response to ASA. METHODS MRP4 mRNA expression has been analyzed by RealTime PCR in platelets from patients on chronic ASA treatment versus a control group. A panel of miRNAs was run on the pool of each cohort. MiRNAs validation was performed by RealTime PCR. To verify whether MRP4 is the target of miR-26b also in platelets, miR-26b was transfected in platelet and DAMI cells with miRNA mimic technology. MRP4 expression was evaluated by flow cytometry and western blotting. RESULTS We observed a higher MRP4 mRNA expression in platelets of patients under ASA treatment compared to the control group (p

Infectious meningitis and encephalitis are potentially life-threatening conditions caused mostly by bacterial and viral agents. Rapid diagnosis and prompt treatment are associated with a more favorable outcome. In recent years nucleic acid amplification tests have been developed to speed detection and identification of pathogens directly from cerebrospinal fluid (CSF). The aim of this study was to compare the diagnostic accuracy of a commercially available multiplex PCR assay for etiological diagnosis of infectious meningitis directly from CSF samples with culture. A secondary endpoint was to look for a possible screening threshold based on main CSF indices and urgent blood test results, to define CSF samples with low pre-test probability of PCR and/or culture-positive result. We performed a secondary analysis of results of CSF samples already processed as part of routine clinical care from February 2016 to December 2018. In all, 109 CSF samples were included in the study and a total of 14 bacteria were identified by either PCR, culture or both methods, along with nine samples positive for viruses. The comparison of PCR results with culture showed no significant difference: 7/109 (6.4%) vs 13/109 (11.9%) respectively, p=0.07. After exclusion of the isolates not detectable by the multiplex PCR panel, the diagnostic accuracy was: 100% (95% confidence interval (CI): 54.1% to 100%) sensitivity; 98.9% (95% CI: 93.5% to 99.9%) specificity; 85.7% (95% CI: 42% to 99.2%) positive predictive value; 100% (95% CI: 95.1% to 100%) negative predictive value; 96 (95% CI: 13.6 to 674.6) LR+; Zero LR-; Cohen's kappa: 0.918, p0.0001. CSF protein value ≤ 28 mg/dl and CSF glucose/blood glucose ratio ≥0.78 were associated with both PCR-negative result for bacteria or viruses and culture-negative result. The multiplex PCR evaluated in this study showed a very good diagnostic performance compared to culture, and the thresholds found can be a useful tool to best choose which samples to test.

Representation in the ROC space of studies in EOS. Representation in the ROC space of studies on PCT for diagnosis of EOS. (ROC, receiver operating characteristic). (PDF 157Â kb)

Forest plot of studies on PCT for diagnosis of sepsis in neonatal age. The forest plot represents in each study the sensitivity and the specificity of PCT, together with the 95% CI for diagnosis of sepsis in neonatal age stratified according cut-off subgroup. (CI, confidence interval; FP, false positive; FN, false negative; PCT, procalcitonin; TP, true positive; TN, true negative). (PDF 743Â kb)

Forest plot of studies on PCT for diagnosis of sepsis in paediatric age. The forest plot represents in each study the sensitivity and the specificity of PCT, together with the 95% CI for diagnosis of sepsis in paediatric age stratified according cut-off subgroup. (PDF 377Â kb)

This work talks about the enhanced neoatherosclerosis after drug-eluting stent implantation by the novel peptide - perilipin 2.

Representation in the ROC space of studies in LOS and paediatric sepsis. Representation in the ROC space of studies on PCT for diagnosis in LOS and paediatric sepsis. (PDF 154Â kb)

Representation in the ROC space of neonatal studies divided in EOS and LOS. Representation in the ROC space of studies on PCT for diagnosis of sepsis in neonatal age, divided by cut-off subgroup and EOS/LOS. (ROC, receiver operating characteristic). (PDF 46Â kb)

Aim : To assess eosinophil cationic protein (ECP) and C-reactive protein (CRP) serum levels at three time points according to different stent types. Methods : 54 patients (age 64 ± 10 years, male 78%), undergoing Bare Metal Stent (BMS) ( n = 11), mammalian Target Of Rapamycin (mTOR)-inhibitor DES ( n = 27) and mTOR-inhibitor bioabsorbable DES (BES) ( n = 16) implantation for stable angina (SA) or non-ST-elevation acute coronary syndromes (NSTE-ACS), were prospectively enrolled. ECP and CRP serum levels were assessed before revascularization, at 1-month and at 1-year after the procedure. Moreover, 21 patients found to have inducible ischemia or angina symptoms at 6 month-stress test underwent 1-year follow-up (FU) angiography. Results : Baseline and 1-month ECP levels were similar among the 3 groups, whilst 1-year ECP was significantly higher in m-TOR-DES [8.61 (6.55–19.77) μg/ml] compared with m-TOR-BES [2.03 (1.78–5.53) μg/ml] and BMS-treated patients [2.23 (1.45–8.95) μg/ml] ( p = 0.02), without significant difference between BES and BMS. CRP was similar among the 3 groups at all time points. 1-year ECP significantly correlated with late loss in patients undergoing FU angiography ( r = 0.64, p = 0.002), while CRP did not ( p = NS). Conclusions : Our finding suggests that mTOR-DES stent type is associated with an increase of ECP levels at 1-year, possibly reflecting a persistent eosinophil activation triggered by permanent polymer.

Clinical examination and m-mode, b-mode, and two-dimensional speckle tracking evaluations with X-Strain® software were carried out in two dogs with dilated cardiomyopathy before and during therapy. During follow-up, the two dogs presented not only in better clinical condition, but also with improvements in m-mode and b-mode indices, as well as increased values of strain and strain rate. Consequently, X-Strain® evaluation should be included in routine echocardiography to better understand the pathogenesis and evolution of disease characterized by reduced myocardial contractility, optimize the therapeutic protocol during follow-up, and contribute to finding the range of normal values for strain and strain rate in the dog.

Congenital cardiac defects are anatomic conditions present at birth. Few references to such conditions in goats are available in the current scientific literature. This report describes, for the first time, a congenital cardiac disease clinically characterized by polypnea from birth and exercise intolerance in a 2-month-old pygmy goat. An atrioventricular dysplasia known as Ebstein's anomaly, an atrial septal defect, and a mild subaortic stenosis were ultrasonographically diagnosed.