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

Bullous pemphigoid, mucous membrane pemphigoid, and pemphigus vulgaris are different cutaneous autoimmune blistering diseases, with complex pathogenic mechanisms. In all of them, a type-2 response is thought to have a central role. Interleukin 4 and Interleukin 13 are crucial cytokines in type-2 response. Treatment of these conditions is often challenging. Dupilumab, a recombinant fully human IgG4 monoclonal antibody with binding specificity to human interleukin-4 receptor IL-4Rα, has the potential to inhibit both IL-4 and IL-13. We propose IL-4Rα as a theoretical drug target for cutaneous autoimmune bullous diseases. K E Y W O R D Sblistering diseases, bullous pemphigoid, dupilumab, mucous membrane pemphigoid, pemphigus vulgaris

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HLA-Cw6 is one of the most strongly associated psoriasis susceptibility alleles. Data regarding correlation between HLA-Cw6 status and biologic treatment outcomes are divergent. The aim of our study in our cohort of psoriatic patients was to explore if the HLA-Cw6 status influences the response rate to biologic therapies at 16 and 48 weeks. One hundred and one psoriatic patients eligible for biologic therapies were enrolled. HLA-C*06 alleles were detected from their blood samples. The effectiveness of antipsoriatic treatments was reported as 90% Psoriasis Area and Severity Index reduction (PASI90). All biologics showed efficacy at week 16, without significant differences between one another. HLA-Cw6 status did not seem to affect baseline characteristics, or treatment response at week 16. At week 48, IL-12/23 and IL-17 targeting drugs were more effective on Cw6-positive patients than on Cw6-negative patients. Conversely, TNF-targeting drugs seemed to be more effective on Cw6- negative patients than on Cw6-positive patients. The HLA-Cw6 test could well deserve to be integrated into the clinical laboratory work-up supporting the choice of the correct biologic.

Infective endocarditis in pregnancy has a low incidence, often being associated with a previous history of rheumatic or congenital heart disease. In most reports the disease tends to run a subacute course and to appear more frequently in the third trimester of pregnancy. We present the case of a 36-year-old woman with large vegetations on the mitral valve due to infective endocarditis detected at the 32nd week of her first pregnancy. The difficulties in selecting the appropriate management strategy, particularly optimal time and mode of delivery, optimal time and type of valve surgery, are emphasized.