Fibrosis-4 (FIB-4) Index and mortality in COVID-19 patients admitted to the emergency department

Liver damage worsens the prognosis of coronavirus 19 disease (COVID-19). However, the best strategy to stratify mortality risk according to liver damage has not been established. The aim of this study is to test the predictive value of the validated Fibrosis-4 (FIB-4) Index and compared it to liver transaminases and to the AST-to-Platelet ratio index (APRI). Multicenter cohort study including 992 consecutive COVID-19 patients admitted to the Emergency Department. FIB-4 > 3.25 and APRI > 0.7 were used to define liver damage. Multivariable Cox regression and ROC curve analysis for mortality were performed. Secondary endpoints were (1) need for high-flow oxygen and (2) mechanical ventilation. 240 (24.2%) patients had a FIB-4 > 3.25. FIB-4 > 3.25 associated with an increased mortality (n = 119, log-rank test p  3.25 was also superior to APRI > 0.7 (AUC 0.58, 95% CI 0.553-0.615, p = 0.0008). Using an optimized cut-off > 2.76 (AUC 0.689, 95% CI 0.659-0.718, p  3.25 (p = 0.0302), APRI > 0.7 (p  51 (p = 0.0119) and ALT > 42 (p < 0.0001). FIB-4 was also associated with high-flow oxygen use (n = 255, HR 1.69, 95% CI 1.25-2.28, p = 0.001) and mechanical ventilation (n = 39, HR 2.07, 95% CI 1.03-4.19, p = 0.043). FIB-4 score predicts mortality better than liver transaminases and APRI score. FIB-4 score may be an easy tool to identify COVID-19 patients at worse prognosis in the emergency department

Urinary 11-dehydro-thromboxane B2 is associated with cardiovascular events and mortality in patients with atrial fibrillation

BACKGROUND: Patients with nonvalvular atrial fibrillation (AF) show high residual cardiovascular (CV) risk despite oral anticoagulants. Urinary 11-dehydro-thromboxane B2 (TxB2) is associated with an increased risk of CV events (CVEs), but its predictive value in patients with anticoagulated AF is unknown. METHODS: A prospective single-center cohort study, including 837 patients with AF, was conducted. Mean time of follow-up was 30.0 months, yielding 2,062 person-years of observation. Urinary 11-dehydro-TxB2 was measured at baseline. The primary end point was the occurrence of a CVE including fatal/nonfatal myocardial infarction and ischemic stroke, transient ischemic attack, cardiac revascularization, and CV death. RESULTS: Mean age of patients was 73.1 years, and 43.6% were women. Median 11-dehydro-TxB2 levels were 100 (interquartile range 50-187) ng/mg of urinary creatinine. Overall, the anticoagulation control was adequate (63.9% of mean time in therapeutic range). A CVE occurred in 99 (11.8%) patients, and 55 were CV deaths. At baseline, 11-dehydro-TxB2 levels were higher in patients with a CVE compared with those without (186 [107-400] vs 98 [52-170], P &lt; .001). An increased rate of CVEs (log-rank test, P &lt; .001) and CV deaths (P &lt; .001) was observed across tertiles of 11-dehydro-TxB2. Cardiovascular events were associated with age (hazard ratios [HR] 1.72 per 1 SD, 95% CI 1.33-2.21, P &lt; .001), diabetes mellitus (HR 1.89, 95% CI 1.20-2.96, P = .005), heart failure (HR 1.60, 95% CI 1.01-2.54, P = .044), history of stroke/transient ischemic attack (HR 1.96, 95% CI 1.25-3.06, P = .003), and 11-dehydro-TxB2 (HR 1.64 per 1 SD, 95% CI 1.42-1.89, P &lt; .001). CONCLUSIONS: Urinary 11-dehydro-TxB2 levels are associated with a residual risk of CVEs and CV mortality in patients with AF despite anticoagulant treatment

Reply to. "monitoring antivitamin K anticoagulants in antiphospholipid syndrome. a challenge in quality"

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Antiphospholipid syndrome and anticoagulation quality: A clinical challenge

BACKGROUND AND AIMS: Antiphospholipid Syndrome (APS) is often complicated by ischemic vascular events. Vitamin K Antagonists (VKAs) reduce the risk of recurrent thrombosis. Quality of VKAs treatment, as assessed by the Time in Therapeutic Range (TTR), has never been investigated in APS patients. METHODS: We performed a prospective observational study including 30 APS and 30 Atrial Fibrillation (AF) patients balanced by age and gender. All patients were treated with VKAs (INR target 2.5), and TTR was calculated. RESULTS: Median TTR of APS was 53.5% vs. 68% of AF patients (p = 0.001). A multivariable linear regression analysis confirmed that the presence of APS (vs. AF) was independently associated with a worse TTR (B: -14.067, 95% Confidence Interval -25.868/-2.266, p = 0.020). The weekly dosage of VKAs was significantly higher in APS than AF patients. CONCLUSIONS: APS patients disclose a lower quality of anticoagulation compared to those with AF, requiring higher doses of VKAs. The efficacy of non-vitamin K oral anticoagulants in this high-risk patients should be tested

Response to "Digoxin or digoxin prescribed patient? Randomized trials are essential to discriminate the principal risk factor for the association of digoxin and increased mortality".

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Features of severe COVID-19: A systematic review and meta-analysis

To systematically review clinical and biochemical characteristics associated with the severity of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease (COVID-19)

Rosuvastatin reduces platelet recruitment by inhibiting NADPH oxidase activation

Rosuvastatin increased vascular endothelial NO and attenuated platelet activation after ischemia-reperfusion in mice; nevertheless, the influence of rosuvastatin on the activation of human platelets and the underlying mechanism has never been investigated. In an in vitro study platelets from 8 healthy donors were incubated with scalar concentrations of rosuvastatin (1-10 mu M) before activation. Platelet recruitment (PR), that mimics the propagation of platelet aggregation and is dependent upon isoprostane formation, was investigated. PR was inhibited by rosuvastatin in concentration-dependent manner concomitantly with down-regulation of platelet release of the pro-thrombotic molecule CD40L. This effect was associated with lower production of platelet reactive oxygen species (ROS), isoprostane and activation of the glycoprotein IIb/IIIa and was counteracted by exogenous addition of isoprostanes. Conversely, rosuvastatin concentration-dependently increased platelet NO. Platelet isoprostane formation mainly depends from NADPH oxidase. Rosuvastatin concentration-dependently inhibited platelet sNOX2-dp release, a specific marker of NADPH oxidase activation, PKC phosphorylation and p47(Phox) translocation from cytosol to membranes. In an ex vivo study 10 hypercolesterolemic patients were randomly allocated to diet or rosuvastatin (20 mg). We observed that as early as 2 h after rosuvastatin PR, platelet isoprostanes formation, platelet CD40L and sNOX2-dp decreased while platelet NO increased; no changes were detected in diet-assigned patients. This study shows that in vitro rosuvastatin impairs platelet activation via inhibition of NOX2-derived oxidative stress. This effect, which is associated ex vivo with acute inhibition of platelet activation, suggests that rosuvastatin behaves as an antiplatelet drug. (C) 2012 Elsevier Inc. All rights reserved

Anti Xa oral anticoagulants inhibit in vivo platelet activation by modulating glycoprotein VI shedding

Anti Xa non-vitamin K oral anticoagulants (anti Xa NOACs) seem to possess antiplatelet effect in vitro, but it is unclear if this occurs also in vivo. Aim of the study was to compare the effect on platelet activation of two anti Xa NOACs, namely apixaban and rivaroxaban, to warfarin, and to investigate the potential underlying mechanism by evaluating soluble glycoprotein GPVI (sGPVI), a protein involved in platelet activation. We performed a cross-sectional including AF patients treated with warfarin (n=30), or apixaban 10mg/day (n=40), or rivaroxaban 20mg/day (n=40). Patients were balanced for sex, age and cardiovascular risk factors. Platelet activation by urinary excretion of 11-dehydro-thromboxane (Tx) B2 and soluble GPVI (sGPVI) were analysed at baseline and after 3 months of treatment. Baseline TxB2 value was 155.2±42.7ng/mg creatinine. The 3 months-variation of urinary excretion of TxB2 was -6.5% with warfarin (p=0.197), -29% with apixaban (p&lt;0.001) and -31% with rivaroxaban (p&lt;0.001). Use of anti Xa NOACs was independently associated to the variation of urinary TxB2 (B: -0.469, p&lt;0.001), after adjustment for clinical characteristics; sGPVI was significantly lower in patients treated with NOACs at 3 months (p&lt;0.001), while only a trend for the warfarin group (p=0.116) was observed. The variation of sGPVI was correlated with that of TxB2 in the NOACs group (Rs: 0.527, p&lt;0.001). In 15 patients (5 per each group) platelet recruitment was significantly lowered at 3 months by NOACs (p&lt;0.001), but not by warfarin. The study provides evidence that anti Xa NOACs significantly inhibit urinary TxB2 excretion compared to warfarin, suggesting that NOACs possess antiplatelet propert

Extra virgin olive oil blunt post-prandial oxidative stress via NOX2 down-regulation.

Objective: Olive oil protects against cardiovascular disease but the underlying mechanism is still unclear. We speculated that olive oil could inhibit oxidative stress, which is believed to be implicated in the atherosclerotic process. Methods and results: Post-prandial oxidative stress and endothelial dysfunction were investigated in twenty-five healthy subjects who were randomly allocated in a cross-over design to a Mediterranean diet added with or without extra virgin olive oil (EVOO, 10 g) (first study, n ¼ 25) or Mediterranean diet with EVOO (10 g) or corn oil (10 g) (second study, n ¼ 25). Oxidative stress biomarkers including platelet reactive oxidant species (ROS) and 8-iso-PGF2a-III, activity of NOX2, the catalytic sub-unit of NADPH oxidase, as assessed in platelets and serum, serum vitamin E and endothelial dysfunction, were measured before and 2 h after lunch. In the first study a significant increase of platelet ROS, 8-iso-PGF2a-III, NOX2 activity, sE-selectin, sVCAM1 and a decrease of serum vitamin E were detected in controls but not when EVOO was included in the Mediterranean diet; oxidative stress and endothelial dysfunction increase were also observed in the second study in subjects given corn oil. A significant correlation was found between NOX2 activity and platelet oxidative stress. In vitro study demonstrated that EVOO but not corn oil significantly decreased platelet and PMNs oxidative stress and NOX2 activity. Conclusion: The study provides the first evidence that post-prandial oxidative stress may be triggered by NOX2 up-regulation. EVOO but not corn oil, is able to counteract such phenomenon suggesting that addition of EVOO to a Mediterranean diet protects against post-prandial oxidative stress