Introduction: Severe COVID-19 patients present with a hypercoagulable state, complement activation and endothelial perturbation, which result from an excessive inflammatory response. Thromboinflammation is one important mechanism underlying the COVID-19-associated coagulopathy and the increased risk of thrombosis. Bergamo city is one of the first and most affected area by SARS-CoV-2 infection in the world. For this reason, since the beginning we were actively involved in recruiting convalescent COVID-19 patients, in a program of selection of candidates for convalescent plasma donation. In a large cohort of convalescent COVID-19 patients, we aimed to characterize markers of coagulation activation and endothelial perturbation, in order to explore whether the COVID-19-related hemostasis activation might persist afterwards and evaluate its possible association with the degree of severity of the previous infection, and/or with demographic characteristics, or anti-SARS-CoV-2 antibody levels. Methods: In 392 convalescent COVID-19 patients (216M/176F, median age: 46 years) plasma levels of fibrinogen, protein C, protein S, factor V, factor VIII, factor XIII, D-dimer, von Willebrand factor (vWF), prothrombin fragment F1+2 were measured at the recruitment, i.e. 1-5 months from recovery. Samples were tested for the anti-SARS-CoV-2 antibodies, including anti-S IgG (Anti-S Ab) and anti-N IgG (Anti-N Ab) antibodies at enrollment and at each scheduled subsequent visits. Results: Levels of fibrinogen, D-dimer, von Willebrand factor, protein S and protein C were significantly higher (p<0.05) in patients who were hospitalized for severe COVID-19 as compared to patients who were treated at home. There was no correlation between levels of coagulation biomarkers and days from end of symptoms. Male gender, age > 40 years, and severe form of COVID-19 were identified as independent predictors of high levels of both anti-S and anti-N Ab (p<0.001). Among hemostatic biomarkers, fibrinogen (p<0.01) and vWF (p<0.05) independently predict high levels of anti-S Ab. In particular, vWF levels positively correlated with anti-S Ab levels (vWF-antigen r=0.188; vWF-activity r=0.241 and vWF-RiCof r=0.223, p<0.01). Evaluation of anti-SARS-CoV2 antibody levels at different time points during follow up revealed that 30% of patients displayed high levels of anti-S Ab until more than 8 months from the end of symptoms. Conclusions: Convalescent patients, with a history of severe COVID-19 had a persistent endothelium activation, despite of disease clinical remission even after 9 months from end of symptoms. Furthermore, fibrinogen and vWF levels predicted high levels of Anti-S Ab. Among demographic characteristics, gender, age and severe disease can be predictors of increased antibody response. These findings suggest that inflammation, coagulation and endothelial dysfunction may persist after recovery and may explain the findings of persistent clinical symptoms reported in these patients after healing from COVID-19. Disclosures Falanga: Bayer: Honoraria; Leo Pharma: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria.
INTRODUCTION AND OBJECTIVE: European guidelines on prostate cancer strongly recommend multiparametric magnetic resonance imaging (mpMRI) before prostate biopsy in patients with clinical suspicion of prostate cancer (PCa). This led to the diffusion of mpMRI even in small non-academic centers. This could have an impact on mpMRI-targeted biopsy (TB) detection rate, given by possible "false positive targets". We aimed to evaluate the PCa detection rate on TB according to the mpMRI canter's volume and experience.METHODS: We retrospectively analyzed data of 737 patients who underwent mpMRI-TB at our clinic for suspicion of PCa, using Toshiba Aplio 500ä mpMRI-TRUS Fusion platform. Transrectal approach was chosen for TB, taking 3 biopsy cores targeted to the index lesion. TB were performed by 4 expert urologists. Specimens were processed by dedicated pathologists. Patients were stratified according to the center in which mpMRI is performed: high volume mpMRI academic (Hub; >300 mpMRI per year) vs. low volume mpMRI non-academic (Spoke; <300 mpMRI per year) centers. In each center, all lesions were scored using the PI-RADS-v2. Differences in detection rate for any PCa and for clinically significant PCa (csPCa) between the two groups were explored. We evaluated predictors of csPCa on TB with multivariable logistic regression. The adjustment for casemix included: age, PSA, mpMRI center (Hub vs. Spoke), lesion's location, PSA density, PI-RADS-v2 score and index lesion's size.RESULTS: Overall, 449 (60.9%) and 288 (39.1%) patients underwent mpMRI at a Hub or Spoke center, respectively. Significantly lower rate of PIRADS 3 lesions were reported in Spoke group compared to Hub group (36.1% vs 49%; p<0.001). Patients in the Hub group had higher detection rate for any PCa (60.3% vs 48.1%) and csPCa (46.9% vs 38.7%; all p 0.001). After stratifying for PI-RADS-v2 score, patients in Hub group had higher detection rate for PI-RADS-v2 score 3 (any PCa 43.6% vs. 28.2% and csPCA 25.2% vs. 15.7%; all p 0.04) and PI-RADS-v2 score 4 (any PCa 74.7% vs. 55% and csPCa 65.7% vs. 45.7%; all p 0.001) compared to patients in Spoke group. At multivariable analyses patients with mpMRI performed in a Spoke center was found to be an independent predictor for detection of csPCa at TB (OR 0.65; p[0.04).CONCLUSIONS: Our study shows that mpMRI performed in Hub centers provided a significantly higher PCa yield on TB. Dedicated radiologist for mpMRI is essential to avoid unnecessary and potentially harmful procedures.
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