Monitoring of cardiovascular risk factors in competitive athletes

It is well known that physical activity can improve cardiovascular risk factors, but it is also true that strenuous activity may result detrimental for the athlete health. Among the emerging markers of cardiovascular risk, plasma homocysteine (Hcy) plays a prominent role, since it has been shown its significant increase in competitive athletes. Some research has concluded that Hcy levels may be influenced by the duration, intensity and type of exercise, whereas other studies have identified lifestyle factors, such as smoking, eating habits, alcohol consumption, age, elevated blood pressure and genetic factors, as factors that contribute to increased plasma concentrations of Hcy. Polymorphisms in the methylenetetrahydrofolate reductase gene (MTHFR) (677C/T, 1298A/C) are reported to modulate homocysteine levels. The aim of this work was to identify a genetic profile of risk for cardiovascular disease in two populations of competitive athletes, football players (n = 19) and those engaged in athletics (n=37). The distribution of MTHFR A1298C and C677T polymorphisms was examined by Real-time PCR allelic discrimination on genomic DNA isolated from lymphocytes of whole peripheral blood. The serum levels of Hcy were determined by HPLC method, while vitamin B12 and folate by RIA technique. The data showed that 50% of the subjects in both groups are carrier of MTHFR C677T polymorphism either in heterozygous or homozygous state. In addition, all subjects had mild hyperhomocysteinemia (13-27 micromol/L). The highest mean levels of Hcy were recorded in the football players, and the differences compared to those engaged in athletics were very significant (21.8 ± 11.6 vs. 13.5 ± 6.6, p <0.05). The increase of Hcy could be ascribed mainly to the diet style of the recruited subjects, characterized by a high consumption of red meat and very low intake of B vitamins. Moreover, this increase may also be explained in relation to the type of exercise required in football, that is considered an intermittent intensity sport. The preliminary results of this study suggest that screening for the MTHFR variants C677T and A1298C should be included in the panel of screening for cardiovascular risk in competitive athletes

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P<0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)

Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial (Journal of Translational Medicine, (2020), 18, 1, (405), 10.1186/s12967-020-02573-9)

Following publication of the original article [1] the authors identified that the collaborators of the TOCIVID-19 investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged. For clarity, all collaborators are listed in this correction article