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).
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In this report we introduce CSF Elastase-alpha 1-Proteinase inhibitor as a valuable indicator for differentiating bacterial meningitis from aseptic meningitis and other neurological disorders. All patients (n = 26) with bacterial meningitis had increased CSF concentrations of E-alpha 1-PI above the range of normal (range of reference values: 0.0-2.3 micrograms/l, n = 79; bacterial meningitis: 30-3490 micrograms/l, n = 26). Concentrations of E-alpha 1-PI in bacterial meningitis were significantly elevated when compared with those in aseptic meningitis (0.0-194 micrograms/l, n = 37), polyneuropathy (0-23 micrograms/l, n = 24) and cerebrovascular attack (0-23.2 micrograms/l, n = 17).
Angiosarcoma is a rare malignancy of vascular origin, mostly originating from skin, soft tissues, and breast, but rarely also from the pleura. We present the case of a 55-year-old man who referred to our hospital for a spontaneous bilateral hemothorax. The CT angiography did not show any source of active bleeding; plus, no pleural or lung masses were observable. Cytological and microbiological analyses made on a sample of pleural fluid resulted negative. Despite numerous blood transfusions and thoracenteses, the patient deceased from hemorrhagic shock ten days later and the diagnosis of primary pleural epithelioid angiosarcoma was obtained only by autopsy. Additionally, we present a review of the literature about primary pleural angiosarcomas.
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