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).

There is the urgent need to study the effects of immunomodulating agents as therapy for Covid-19. An observational, cohort, prospective study with 30 days of observation was carried out to assess clinical outcomes in 88 patients hospitalized for Covid-19 pneumonia and treated with canakinumab (300 mg sc). Median time from diagnosis of Covid-19 by viral swab to administration of canakinumab was 7.5 days (range 0–30, IQR 4–11). Median PaO2/FiO2 increased from 160 (range 53–409, IQR 122–210) at baseline to 237 (range 72–533, IQR 158–331) at day 7 after treatment with canakinumab (p < 0.0001). Improvement of oxygen support category was observed in 61.4% of cases. Median duration of hospitalization following administration of canakinumab was 6 days (range 0–30, IQR 4–11). At 7 days, 58% of patients had been discharged and 12 (13.6%) had died. Significant differences between baseline and 7 days were observed for absolute lymphocyte counts (mean 0.60 vs 1.11 × 109/L, respectively, p < 0.0001) and C-reactive protein (mean 31.5 vs 5.8 mg/L, respectively, p < 0.0001).Overall survival at 1 month was 79.5% (95% CI 68.7–90.3). Oxygen-support requirements improved and overall mortality was 13.6%. Confirmation of the efficacy of canakinumab for Covid-19 warrants further study in randomized controlled trials.

The proposed grading system allows to stratify for ischemic complications in MMD patients that receive bilateral, one-staged revascularization surgery. Future studies will have to investigate its use for predicting ischemic complications in other revascularization strategies for MMD.

Background The introduction of exoscopes in neurosurgery has been welcomed due to their maneuverability, ergonomics, and low-profile frame. 3D devices have further enabled a better stereoscopic visualization. Reports on their application, albeit more and more frequent, are still at their beginning stages. We present our experience with the Olympus ORBEYE 4K-3D exoscope for major cranial procedures. The strengths and weaknesses of the exoscope are presented, and the nuances associated with the learning curve are illustrated. Methods Over 2 weeks, patients undergoing surgery for major cranial pathologies were offered to participate in this evaluation of the Olympus ORBEYE 4K-3D exoscope. Information on the use of the exoscope was collected to assess the features and struggles in the learning curve. A comparison with the operating microscope was made. Results Fourteen patients with different intracranial pathologies were operated on with the exoscope. No surgery-related complications occurred. The microsurgical part was performed with the exoscope in six cases. The exoscope was used for 72.9% (±37.5%) of the whole microsurgical time vs. 27.1% (±37.5%) microscope time (p = 0.02). Conclusion The Olympus ORBEYE 4K-3D exoscope represents a useful evolution of the operating microscope. It requires time to overcome potential difficulties, mostly related to previous motor schemes acquired with operating microscopes. Its features could represent the basis for a paradigm shift in microsurgery.

In this multicentre retrospective study, patients with viraemia >500,000 copies/ml who start a first-line regimen containing PI+INI or NNRTI yield a better VS compared to those receiving a PI-based regimen.