Evaluation of accuracy and reproducibility in manual point picking during 3D cephalometry on CBCT data

Three-dimensional cephalometry is currently emerging as an innovative diagnos- tic tool, due to accessibility and radiation low dose of Cone Beam CT (CBCT) scan ners (1). Despite annotation made by specialists is now considered the gold standard in clinical practice and research, reliability of manual point picking can be biased by intra and inter-operator differences (2). In order to estimate the variability of the manual procedure, in this study an evaluation of accuracy, precision and reproducibility was performed. Three experienced operators analyzed ten CBCT images, retrospectively selected from the SST Dentofacial Clinic database. They annotated 9 chosen landmarks on all the images for three times, under the same conditions and at least one week of distance. Accuracy and precision were calculated as the median and the interquartile range of the distances from each landmark to the corresponding barycenter, calculated as the mean of all operator annotations. Kruskal-Wallis test was performed to evaluate reproducibility, and post-hoc tests were carried out to assess whether the significance depended from operators. A remarkable difference was found in accuracy between anatomic and geometrical landmarks, in both the intra and inter-operator repetitions. The intra-operator analysis showed higher accuracy and precision values than the inter-operator one. Statistical analyses revealed significant differences in reproducibility (p<0.05) for all landmarks except for Sella turcica, but the post-hoc tests did not show a clear pattern between operators. Results demonstrate that both accuracy and reproducibility may vary, depending on the operators, suggesting the need for automatic or semiautomatic tools that will help the operator during annotation

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA 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.ResultsIn 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.ConclusionsTocilizumab 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)

Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial (Journal of Translational Medicine, (2020), 18, 1, (405), 10.1186/s12967-020-02573-9)

Following publication of the original article [1] the authors identified that the collaborators of the TOCIVID-19 investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged. For clarity, all collaborators are listed in this correction article