Coronavirus disease 2019 (COVID-19) may have a wide spectrum of clinical presentations, leading in some cases to a critical condition with poor long-term outcomes and residual disability requiring post-acute rehabilitation. A major concern in severe COVID-19 is represented by a concomitant prothrombotic state. However, contrasting data are available about the prevalence of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and/or pulmonary embolism (PE). A detailed search on the association of COVID-19 with thromboembolic complications was conducted in the main electronic databases (PubMed, Web of Science, and Scopus) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The weighted mean prevalence (WMP) with 95% confidence interval (95% CI) was calculated with the random-effects model. Twenty studies enrolling 1,988 COVID-19 patients were included. The WMP of VTE was 31.3% (95% CI: 24.3–39.2%). The WMP of DVT was 19.8% (95% CI: 10.5–34.0%), whereas the WMP of PE was 18.9% (95% CI: 14.4–24.3%). Similar results were obtained when specifically analyzing studies on patients admitted to intensive care units and those on patients under antithrombotic prophylaxis. Regression models showed that an increasing age was associated with a higher prevalence of VTE (Z-score: 3.11, p = 0.001), DVT (Z-score: 2.33, p = 0.002), and PE (Z-score: 3.03, p = 0.002), while an increasing body mass index was associated with an increasing prevalence of PE (Z-score = 2.01, p = 0.04). Male sex did not impact the evaluated outcomes. The rate of thromboembolic complications in COVID-19 patients is definitely high. Considering the risk of fatal and disabling complications, adequate screening procedures and antithrombotic strategies should be implemented.

Background: Endothelial dysfunction has a key role in the pathogenesis of coronavirus disease 2019 (COVID-19) and its disabling complications. We designed a case-control study to assess the alterations of endothelium-dependent flow-mediated dilation (FMD) among convalescent COVID-19 patients. Methods: COVID-19 patients referred to a Pulmonary Rehabilitation Unit within 2 months from swab test negativization were consecutively evaluated for inclusion and compared to controls matched for age, gender, and cardiovascular risk factors. Results: A total of 133 convalescent COVID-19 patients (81.2% males, mean age 61.6 years) and 133 matched controls (80.5% males, mean age 60.4 years) were included. A significantly lower FMD was documented in convalescent COVID-19 patients as compared to controls (3.2% ± 2.6 vs. 6.4% ± 4.1 p < 0.001), confirmed when stratifying the study population according to age and major clinical variables. Among cases, females exhibited significantly higher FMD values as compared to males (6.1% ± 2.9 vs. 2.5% ± 1.9, p < 0.001). Thus, no significant difference was observed between cases and controls in the subgroup analysis on females (6.1% ± 2.9 vs. 5.3% ± 3.4, p = 0.362). Among convalescent COVID-19 patients, FMD showed a direct correlation with arterial oxygen tension (rho = 0.247, p = 0.004), forced expiratory volume in 1 s (rho = 0.436, p < 0.001), forced vital capacity (rho = 0.406, p < 0.001), and diffusing capacity for carbon monoxide (rho = 0.280, p = 0.008). Overall, after adjusting for major confounders, a recent COVID-19 was a major and independent predictor of FMD values (β = −0.427, p < 0.001). Conclusions: Post-acute COVID-19 syndrome is associated with a persistent and sex-biased endothelial dysfunction, directly correlated with the severity of pulmonary impairment.

For many years, it has been recognized that hypertension tends to cluster with various anthropometric and metabolic abnormalities including abdominal obesity, elevated triglycerides, reduced high-density lipoprotein cholesterol, glucose intolerance, insulin resistance and hyperuricemia. This constellation of various conditions has been transformed from a pathophysiological concept to a clinical entity, which has been defined metabolic syndrome (MetS). The consequences of the MetS have been difficult to assess without commonly accepted criteria to diagnose it. For this reason, on 2009 the International Diabetes Federation, the American Heart Association and other scientific organizations proposed a unified MetS definition. The incidence of the MetS has been increasing worldwide in parallel with an increase in overweight and obesity. The epidemic proportion reached by the MetS represents a major public health challenge, because several lines of evidence showed that the MetS, even without type 2 diabetes, confers an increased risk of cardiovascular morbidity and mortality in different populations including also hypertensive patients. It is likely that the enhanced cardiovascular risk associated with MetS in patients with high blood pressure may be largely mediated through an increased prevalence of preclinical cardiovascular and renal changes, such as left ventricular hypertrophy, early carotid atherosclerosis, impaired aortic elasticity, hypertensive retinopathy and microalbuminuria. Indeed, many reports support this notion, showing that hypertensive patients with MetS exhibit, more often than those without it, these early signs of end organ damage, most of which are recognized as significant independent predictors of adverse cardiovascular outcomes.

Background: Complications of coronavirus disease 2019 (COVID-19) include coagulopathy. We performed a meta-analysis on the association of COVID-19 severity with changes in hemostatic parameters. Methods: Data on prothrombin time (PT), activated partial thromboplastin time (aPTT), D-Dimer, platelets (PLT), or fibrinogen in severe versus mild COVID-19 patients, and/or in non-survivors to COVID-19 versus survivors were systematically searched. The standardized mean difference (SMD) was calculated. Results: Sixty studies comparing 5487 subjects with severe and 9670 subjects with mild COVID-19 documented higher PT (SMD: 0.41; 95%CI: 0.21, 0.60), D-Dimer (SMD: 0.67; 95%CI: 0.52, 0.82), and fibrinogen values (SMD: 1.84; 95%CI: 1.21, 2.47), with lower PLT count (SMD: −0.74; 95%CI: −1.01, −0.47) among severe patients. Twenty-five studies on 1511 COVID-19 non-survivors and 6287 survivors showed higher PT (SMD: 0.67; 95%CI: 0.39, 0.96) and D-Dimer values (SMD: 3.88; 95%CI: 2.70, 5.07), with lower PLT count (SMD: −0.60, 95%CI: −0.82, −0.38) among non-survivors. Regression models showed that C-reactive protein values were directly correlated with the difference in PT and fibrinogen. Conclusions: Significant hemostatic changes are associated with COVID-19 severity. Considering the risk of fatal complications with residual chronic disability and poor long-term outcomes, further studies should investigate the prognostic role of hemostatic parameters in COVID-19 patients.

Background: Growing evidence points to a key role of endothelial dysfunction in the pathogenesis of COVID-19. In this study, we evaluated changes in endothelium-dependent flow-mediated dilation (FMD) in a cohort of convalescent COVID-19 patients undergoing pulmonary rehabilitation (PR). Methods: After swab test negativization, convalescent COVID-19 patients referring to a post-acute care facility for PR were consecutively screened for inclusion. Study procedures were performed at the time of hospitalization and discharge. Results: We enrolled 82 convalescent COVID-19 patients (85.4% males, mean age 60.4 years). After PR, a significant improvement in most pulmonary function tests and exercise capacity was documented. FMD changed from 2.48% ± 2.01 to 4.24% ± 2.81 (p < 0.001), corresponding to a 70.9% increase. Significantly higher changes in FMD were found in patients without a history of vascular events as compared to those with (+2.04% ± 2.30 vs. +0.61% ± 1.83, p = 0.013). Values of forced expiratory volume in 1 s (FEV1%), forced vital capacity (FVC%) and diffusion capacity for carbon monoxide (DLCO%) significantly and directly correlated with FMD both at baseline and after PR. Patients with normal FEV1% (≥80% predicted) during the overall study period or those normalizing FEV1% after PR showed a more significant FMD change as compared to patients with persistently impaired FEV1% (<80% predicted) (p for trend = 0.029). This finding was confirmed in a multivariate analysis. Conclusions: Clinically evaluated endothelial function improves after PR in convalescent COVID-19 patients. A direct and persistent association between the severity of pulmonary and vascular disease can be hypothesized. Endothelial function testing may be useful in the follow-up of convalescent COVID-19 patients.

Despite an increasing access to prophylaxis with clotting factor concentrates, arthropathy still represents the main chronic complication of hemophilia. Whereas previous studies described hemophilic arthropathy (HA) as a degenerative arthropathy, somehow resembling osteoarthritis (OA), most recent evidence suggests that complex inflammatory and immunologic mechanisms are also involved in the pathophysiology of HA. In the present review, we described available data on major mechanisms leading to arthropathic changes in patients with hemophilia, with a specific focus on the role of synovium. The presence of hemosiderin in the joint space induces synovium proliferation, thus leading to formation of several lytic enzymes determining chondrocytes apoptosis and proteoglycans levels reduction. This leads to a direct joint "chemical" damage representing early damages in the pathogenesis of HA (first hit). In parallel, synovial membrane and synovial endothelial cells become a dynamic reservoir of inflammatory cells and mediators, and propagate the inflammatory response (second hit), switching the process from a chemical damage to an inflammatory damage. Overall, consistent data pointed out synovitis as the keystone in HA pathophysiology. This opens novel potential therapeutic targets in this clinical setting.

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Limited and conflicting data are available about the association between short-term blood pressure (BP) variability and urinary albumin excretion rate (uAER). The objective of our study was to analyze the relationships between microalbuminuria (MAU), defined as an uAER between 20 and 200 μg min(-1), and short-term BP variability (BPV), assessed as average real variability (ARV), weighted s.d. of 24-h BP and as s.d. of daytime and night-time BP. The study population consisted of 315 untreated essential hypertensives with normal estimated glomerular filtration rate (>60 ml min(-1) per 1.73 m(2)), who underwent 24-h ambulatory BP monitoring and 24-h uAER determination. MAU was detected in 82 (26%) patients. ARV of 24-h systolic BP (SBP) was significantly higher in patients with MAU (9.8 (8.5-11.1) mm Hg) when compared with those without it (9.1 (8-10.2) mm Hg; P=0.007). This difference held (P=0.026) after adjustment for age, mean levels of BP and other potential confounders by analysis of covariance. A statistically significant correlation was also found between ARV of 24-h SBP and uAER (r=0.17; P=0.003). This association remained significant (β=0.15; P=0.01), also taking into account the effect of 24-h average systolic and diastolic BP, age, gender, diabetes, serum uric acid, triglycerides, estimated glomerular filtration rate in multiple regression analyses. All the other indices of short-term BPV tested were not independently associated with MAU. Our results seem to suggest that in essential hypertension, short-term BPV, only when estimated by ARV of 24-h SBP, is independently associated with MAU.