Transcatheter aortic valves produce unphysiological flows which may contribute to thromboembolic events: An in-vitro study.

PURPOSE: Transcatheter aortic valve implantation (TAVI) has been associated with large incidence of ischemic events, whose sources are still unclear. In fact, sub-acute complications cannot be directly related to the severity of the calcification in the host tissues, nor with catheter manipulation during the implant. A potential cause could be local flow perturbations introduced by the implantation approach, resulting in thrombo-embolic consequences. In particular, contrary to the surgical approach, TAVI preserves the presence of the native leaflets, which are expanded in the paravalvular space inside the Valsalva sinuses. The purpose of this study is to verify if this configuration can determine hemodynamic variations which may promote blood cell aggregation and thrombus formation. METHODS: The study was performed in vitro, on idealized models of the patient anatomy before and after TAVI, reproducing a range of physiological operating conditions on a pulse duplicator. The fluid dynamics in the Valsalva sinuses was analyzed and characterized using phase resolved Particle Image Velocimetry. RESULTS: Comparison of the flow downstream the valve clearly indicated major alterations in the fluid mechanics after TAVI, characterized by unphysiological conditions associated with extended stagnation zones at the base of the sinuses. CONCLUSION: The prolonged stasis observed in the Valsalva sinuses for the configuration modelling the presence of transcatheter aortic valves provides a fluid dynamic environment favourable for red blood cell aggregation and thrombus formation, which may justify some of the recently reported thromboembolic and ischemic events. This suggests the adoption of anticoagulation therapies following TAVI, and some caution in the patients׳ selection

Sofosbuvir-based therapies in genotype 2 hepatitis C virus cirrhosis: A real-life experience with focus on ribavirin dose

This study aimed to investigate the efficacy and safety of sofosbuvir-based therapies for the treatment of cirrhosis from hepatitis C virus (HCV) genotype 2 infection. Data of all consecutive HCV genotype 2 cirrhotic patients who started sofosbuvir-based treatments between January 2015 and March 2017 in eight Italian tertiary hospitals were collected retrospectively. Overall, 273 patients (Child A: 94.5%) were enrolled. In the 194 subjects treated with sofosbuvir/ribavirin, median initial ribavirin dosage was 13.9 mg/kg/day, and therapy duration was 16 weeks. Sustained virological response (SVR) rates were 93.8% in intention-to-treat (ITT) and 95.3% in per-protocol (PP) analyses for the 129 treatment-naïve patients, and 96.9% (ITT) and 98.4% (PP) for the 65 treatment-experienced subjects. Adverse events were reported in 142 patients (73.2%), but only 1.5% discontinued treatment. Eighty-eight subjects with treatment-induced anemia (mild: 34.5%, moderate: 7.7%, severe: 3.1%) had to reduce ribavirin dosage, but SVR rates were comparable to the weight-based dose group, both in ITT (95.4% and 94.3%) and PP (97.7% and 95.2%) analyses, respectively. Moreover, ITT and PP SVR rates were similar between shorter (<20 weeks) (94.1% and 96.0%, respectively) and prolonged (≥20 weeks) regimens (95.7% and 96.7%, respectively). SVR rates in the 79 subjects treated with sofosbuvir/daclatasvir (without ribavirin) were similar (ITT: 96.2%; PP: 97.4%, respectively), without de novo/worsening anemia. In conclusion, in a real-life study centered on genotype 2 patients with well-compensated cirrhosis, sofosbuvir-based regimens were associated with good SVR and tolerability rates, regardless of previous antiviral treatments, without a significant impact of on treatment ribavirin dose reductions

SAT0460 INGESTION OF LEMON JUICE MAY MODULATE BONE METABOLISM.

Background:An association between bone health and consumption of citrus fruits have been previously reported; however, the effect of lemon juice on bone metabolism have not been explored yet.Objectives:To investigate bone metabolic changes in postmenopausal women assuming lemon juice.Methods:Participants were postmenopausal osteoporotic women without history of clinical fractures who agreed to enrich their diet with lemon juice (Acti Lemon, Polenghi) over a 2-month period. The daily juice dose of 30 ml we suggested was equivalent to one Sicilian organic lemon. Surrogate markers of bone formation as procollagen type 1 N-propeptide (P1NP) and of bone resorption as C-terminal telopeptide of type I collagen (CTX), but also some regulators of bone metabolism as RANK-L, OPG, RANK-L/OPG ratio and sclerostin were assessed at baseline and then at 1 and 2 months after lemon juice administration. Controls were represented by a placebo group of age-matched osteoporotic postmenopausal women.Results:47 participants [mean age 60.2 ± 4.1 yr.] completed the study, without reporting any adverse events. Lemon juice was well tolerated. Over the observation period modifications of bone metabolism occurred: we detected a decreased RANK-L/OPG ratio and increased CTX levels at all time points vs. baseline. Particularly, change at month-1 of sclerostin (versus baseline) has been positively associated with change at month-1 and month-2 of CTX (r=0.46, p=0.01 and r=0.43, p=0.01, respectively). Change at month-1 of OPG was positively associated with change at month-1 of P1NP (r=0.49, p=0.006). Change at month-1 of RANKL/OPG has been related with variation at day 30 of P1NP (r=-0.44, p=0.013). Variation of P1NP at month-1 was related with sclerostin variation at day 30 (r=-0.56, p=0.02) and month-2 vs. baseline value (r=0.44, p=0.017) and with sclerostin variation between month-1 and month-2 (r=0.69, p<0.001). Variation of P1NP between month-1 and month-2 was associated with RANKL change at month-1 (r=-0.35, p=0.05), with sclerostin change at month-1 (r=-0.49, p=0.008) and with sclerostin change between month-1 and month-2 (r=0.41, p=0.028). At a multiple regression analysis the change of P1NP between month-1 and month-2 was independently predicted by the change of sclerostin at month-1 (ß=-1.5, SE 0.5, p=0.006), after correcting for age, BMI and change of RANKL and CTX levels at month-1. No significant modifications raised from controls.Conclusion:Drinking lemon juice may boost bone metabolic changes involving both bone resorption and bone formation.Disclosure of Interests:None declare

17β-Oestradiol Protects from Hepatitis C Virus Infection through Induction of Type I Interferon

Background and Aims: Sex hormones are widely recognised to act as protective factors against several viral infections. Specifically, females infected by the hepatitis C virus display higher clearance rates and reduced disease progression than those found in males. Through modulation of particle release and spread, 17β-oestradiol controls HCV’s life cycle. We investigated the mechanism(s) behind oestrogen’s antiviral effect. Methods: We used cell culture-derived hepatitis C virus in in vitro assays to evaluate the effect of 17β-oestradiol on the innate immune response. Host immune responses were evaluated by enumerating gene transcripts via RT-qPCR in cells exposed to oestrogen in the presence or absence of viral infection. Antiviral effects were determined by focus-forming unit assay or HCV RNA quantification. Results: Stimulation of 17β-oestradiol triggers a pre-activated antiviral state in hepatocytes, which can be maintained for several hours after the hormone is removed. This induction results in the elevation of several innate immune genes, such as interferon alpha and beta, tumour necrosis factor, toll-like receptor 3 and interferon regulatory factor 5. We demonstrated that this pre-activation of immune response signalling is not affected by a viral presence, and the antiviral state can be ablated using an interferon-alpha/beta receptor alpha inhibitor. Finally, we proved that the oestrogen-induced stimulation is essential to generate an antiviral microenvironment mediated by activation of type I interferons. Conclusion: Resulting in viral control and suppression, 17β-oestradiol induces an interferon-mediated antiviral state in hepatocytes. Oestrogen-stimulated cells modulate the immune response through secretion of type I interferon, which can be countered by blocking interferon-alpha/beta receptor alpha signalling

A gas chromatography-mass spectrometry untargeted metabolomics approach to discriminate Fiore Sardo cheese produced from raw or thermized ovine milk.

Thermization is a sub-pasteurization heat treatment of cheese milk (at 57-68°C for 15-30 s) aimed to reduce the number of undesirable microbial contaminants with reduced heat damage to the indigenous milk enzymes. In this work, the effects of milk thermization on the compositional parameters, proteolysis indices, free fatty acid levels, and low molecular weight metabolite profiles of ovine cheese were studied. Cheese samples at different ripening stages and produced in 2 different periods of the year were analyzed. While the effects of milk thermization on cheese macro-compositional parameters and free fatty acid levels were not evident due to the predominant effects of milk seasonality and cheese ripening stage, the gas chromatography-mass spectrometry based metabolomics approach of ovine cheese produced from raw and thermized milk highlighted strong differences at the metabolite level. Discriminant analysis applied to gas chromatography-mass spectrometry data provided an excellent classification model where cheese samples were correctly classified as produced from raw or thermized milk. The metabolites that mostly changed due to the thermization process belonged to the classes of free amino acids and saccharides. Gas chromatography-mass spectrometry-based metabolomics has proven to be a valid tool to study the effect of mild heat treatments on the polar metabolite profile in ovine cheese

Facteurs de production et qualité sensorielle des fromages

Cette revue fait le point sur les connaissances acquises au cours des 10 dernières années sur les relations entre les facteurs de conduite des animaux (génétiques, physiologiques, alimentaires) et la qualité sensorielle des fromages. Chez la vache, avec des fabrications au lait entier, la race peut modifier les caractéristiques de texture des fromages. Cet effet est essentiellement lié aux différences de composition chimique des laits et donc de gras/sec des fromages. Au sein d'une même race, des différences importantes de texture et de goût ont été observées en fonction des variants génétiques de la caséine β (espèce bovine) et surtout αs1 (espèce caprine). Le stade physiologique n'a un effet marqué sur la couleur, la texture et le goût qu'en tout début ou en toute fin de lactation. En revanche, les mammites ont un effet négatif important sur les caractéristiques sensorielles des fromages. L'utilisation d'ensilage de maïs conduit toujours à des fromages plus blancs et parfois à des différences de flaveur. Lorsqu'elle est correctement réalisée, la conservation de l'herbe sous forme d'ensilage comparativement au foin ne modifie pas ou peu les caractéristiques sensorielles des fromages, en dehors de leur couleur, plus jaune avec l'ensilage. Par contre, d'importantes différences de caractéristiques sensorielles sont observées entre des fromages selon que le lait provient de vaches recevant une ration à base d'herbe conservée ou conduites au printemps, au pâturage. Plusieurs essais récents ont mis en évidence un effet de la composition botanique des fourrages ingérés par les vaches laitières sur la texture et la flaveur des fromages. Ces différents effets sont dus à la présence dans le lait de molécules ou de structures issues directement de l'alimentation (carotènes, terpènes) ou produites par l'animal (plasmine, acides gras, structure des micelles de la caséine) en raison de ses caractéristiques génétiques ou physiologiques ou sous l'effet d'une alimentation spécifique

Modelling hospital bed necessity for COVID-19 patients during the decline phase of the epidemic trajectory

BACKGROUND: In the present study we aimed to create a model able to predict the short-term need of hospital beds for COVID-19 patients, during SARS-CoV-2 outbreak. METHODS: We retrospectively revised data about all COVID-19 patients hospitalized at a University Hospital in Northern Italy, between March 1 and April 29, 2020. Several polynomial models (from first to fourth order) were fitted to estimate the relationship between the time and the number of occupied hospital beds during the entire period and after the local peak of the outbreak and to provide the prediction of short-term hospital beds demand. Model selection was based on the adjusted R2 (aR2) Index and likelihood ratio test (LRT). RESULTS: We included 836 hospitalizations (800 COVID-19 patients). The median length of hospital in-stay was 12 days. According to the aR2, the fourth order models best fitted the data considering the entire time period. When only the data after the peak was selected, no statistical improvement was found adding terms of order 3 and 4 and lower order polynomial models were considered for the forecasting of the hospital beds demand. Both approaches had a decreasing trend in the number of occupied beds along with time; however, the quadratic one showed a faster reduction in the predicted number of beds required by patients affected by COVID-19. CONCLUSIONS: We propose a model to predict the hospital bed requirement during the descending phase of COVID-19 outbreak, the validation of which might contribute to decision makers policy in the next weeks of pandemic