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).
Anisakis pathology is due mainly to two mechanisms: allergic reactions (from isolated urticaria and angioedema to life-threatening anaphylactic shock associated with gastrointestinal symptoms or 'gastroallergic anisakiasis'), and direct tissue damage, due to invasion of the gut wall, development of eosinophilic granuloma, or perforation (gastric or intestinal anisakiasis). Anisakiasis is a misdiagnosed and underestimated cause of acute abdomen: most patients undergo laparotomy, and virtually no cases are diagnosed before surgery. In some cases, diagnosis is obtained accidentally during other pathologic investigations. We report a case of acute abdomen due to terminal ileum involvement. Microscopic examination of the resected segment showed the presence of helminthic sections consistent with larvae of Anisakis spp. A history of raw fish ingestion was recorded. Histopathologic features are illustrated. A short but up-to-date review of the literature on diagnostic devices (particularly imaging and serology), clinical aspects and therapy is presented.
We measured severe acute respiratory syndrome coronavirus 2 spike protein subunits S1/S2 antibodies by using capillary electrophoresis and a chemiluminescence immunoassay for 5,444 active healthcare workers in Italy. Seroprevalence was 6.9% and higher among participants having contact with patients. Seroconversion was not observed in 37/213 previously infected participants.
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