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Background: Carotid endarterectomy (CEA) for the prevention of upcoming vascular and cerebral events is necessary in patients with high-grade stenosis (=70%). In the framework of the Italian National project Age.It, a pilot study was proposed aiming at the discovery of amolecular signature with predictive potential of carotid stenosis comparing 65+ asymptomatic and symptomatic inpatients. Methods: A total of 42 inpatients have been enrolled, including 26 men and 16 women, with a mean age of 74 ± 6 years. Sixteen symptomatic and 26 asymptomatic inpatients with =70% carotid stenosis underwent CEA, according to the recommendations of the European Society for Vascular Surgery and the Society for Vascular Surgeons. Plaque biopsies and peripheral blood samples from the same individuals were obtained. Hematobiochemical analyses were conducted on all inpatients, and plasma cytokines/molecules, such as microRNAs (miRs), IL-6, sIL-6Ralpha, sgp130, myostatin (GDF8), follistatin, activin A, CXCL9, FGF21, and fibronectin, were measured using the ELISA standard technique. MiR profiles were obtained in the discovery phase including four symptomatic and four asymptomatic inpatients (both plasma and plaque samples), testing 734 miRs. MiRs emerging from the profiling comparison were validated through RT-qPCR analysis in the total cohort. Results and conclusion: The two groups of inpatients differ in the expression levels of blood c-miRs-126-5p and -1271-5p (but not in their plaques), which are more expressed in symptomatic subjects. Three cytokines were significant between the two groups: IL-6, GDF8, and CXCL9. Using receiver operating characteristic (ROC) analysis with a machine learning-based approach, the most significant blood molecular signature encompasses albumin, C-reactive protein (CRP), the percentage of monocytes, and CXCL9, allowing for the distinction of the two groups (AUC = 0.83, 95% c.i. [0.85, 0.81], p = 0.0028). The potential of the molecular signature will be tested in a second cohort of monitored patients, allowing the application of a predictive model and the final evaluation of cost/benefit for an assessable screening test. [ABSTRACT FROM AUTHOR]

Idiopathic inflammatory myopathies (IIMs) are a group of rare diseases characterized by muscle pain and weakness associated with lymphocyte infiltration in the muscle tissue. Etiopathogenesis is not yet fully understood and the diagnosis is long-lasting and costly, often leading to a delay in the therapy. The diagnosis requires several steps, including an accurate clinical and laboratory investigation, EMG and muscle biopsy. The latter permits to define the diagnosis, distinguishing between IIM and hereditary myopathies, but it is an invasive procedure. The identification of new biomarkers able to differentiate patients with myositis by simple, low cost and non-invasive tests could improve the diagnostic efficiency, reducing the time to diagnosis/handling patients, and the costs generated by wrongly or untreated patients. MicroRNAs (miRs) are post transcriptional regulators of gene expression and the circulating ones are appealing non-invasive potential biomarkers. We have analyzed the expression of plasma circulating-miRs (cmiRs) in patients with or without IIM, compared with healthy subjects, and we have identified an index, based on the ratio between two c-miRs, which is able to distinguish with high specificity and sensitivity among patients with IIM or with other neuromuscular disorders with clinical signs similar to myositis. The study has been conducted in blind and confirmed by standard diagnostic tools. The index, based on a simple and rapid method of analysis, is patent protected and has a great potential as non-invasive diagnostic biomarkers for IIMs. Current experiments are focused on the identification of molecular mechanisms underpinning the alteration of the two identified c-miRs. [ABSTRACT FROM AUTHOR]