Background
Tocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.
Methods
A 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.
Results
In 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.
Conclusions
Tocilizumab 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).
Rhodococcus equi is a gram-positive, coryneform bacterium that causes zoonotic infection mainly in horses and foals. It sometimes affects humans presenting as cavitary pneumonia. Immunocompromised patients, including HIV-infected patients, are more susceptible to R. equi infection. We present 10 cases of R. equi infection in HIV-positive patients admitted to our institute from 1991 to June 2008. Moreover, we have reviewed 272 cases of R. equi infection in HIV-infected persons, published from 1986 through 2008. With respect to the literature data, the R. equi strains isolated in our case series showed lower sensitivity to ceftriaxone, amoxicillin/clavulanic acid, and cotrimoxazole. Prompt diagnosis, early initiation of antiretroviral treatment and combined antimicrobial treatment seem to be effective to eradicate the infection and to improve the outcome.
A small urachal remnant, especially at birth, may be viewed as physiological. Urachal remnants in patients younger than 6 months are likely to resolve with nonoperative management. However, if symptoms persist or the urachal remnant fails to resolve after 6 months of age, it should be excised to prevent recurrent infections.
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