This review summarizes boronic acid's contribution to the development of bioconjugates with a particular focus on the molecular mechanisms underlying its role in the construction and function of the bioconjugate, namely as a bioconjugation warhead, as a payload and as part of a bioconjugate linker.
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).
Psoriasis is a chronic, immune-mediated inflammatory skin disease which is associated with a substantial detriment to physical and psychological quality of life (Cozzani et al., 2010). For this reason, it is imperative to find an effective and safe therapy.A new class of biologic therapy that targets IL-17A has been discovered. One of these agents, secukinumab (Novartis Pharmaceuticals), is an injectable, fully human monoclonal antibody and was recently approved by the US Food and Drug Administration for treat-
COVID-19 "second wave" and vaccines: the dermatologists' perspective Dear Editor, Coronavirus disease 2019 (COVID-19) has affected tens of millions of people worldwide since it was declared a pandemic by the World Health Organization on March 11, 2020. During
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.