The Robotic Intracorporeal Vesuvian Orthotopic Neobladder (VON)—A New Technique for Continent Urinary Diversion: Initial Experience and Description of the Technique

Orthotopic neobladder reconstruction is becoming an increasing option as a urinary diversion following cystectomy for bladder cancer. The purpose of the following article is to describe, step-by-step, our technique for the robotic intracorporeal neobladder, the Vesuvian Orthotopic Neobladder. The primary aim of this new surgical procedure is to simplify and speed up the reservoir reconstruction, while at the same time obtaining an appropriate reservoir capacity. The Vesuvian Orthotopic Neobladder was performed employing an intestinal tract of 36 cm which was successively shaped in order to form a reservoir with three horns (left, right, and caudal), formed via the use of a mechanical stapler. Both ureters were stented and anastomosed to the left and right horn while the urethral-neobladder anastomosis was performed with the caudal horn. In this initial experience, two male patients with non-metastatic muscle-invasive bladder cancer underwent radical cystectomy followed by Vesuvian Orthotopic Neobladder reconfiguration. The mean age was 58.5 ± 3.53 years while the mean overall operative time was 435 ± 35.35 min, with an average neobladder reconstruction time of 59 ± 4.24 min. No intraoperative or postoperative complications were reported. The new intracorporeal Vesuvian Orthotopic Neobladder technique is a feasible and good alternative to traditional robotic intracorporeal orthotopic bladder procedures, permitting us to reduce operative time and obtain a neobladder with a fair reservoir capacity

TGFβ responsive tyrosine phosphatase promotes rheumatoid synovial fibroblast invasiveness

In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLS) that line joint synovial membranes aggressively invade the extracellular matrix, destroying cartilage and bone. As signal transduction in FLS is mediated through multiple pathways involving protein tyrosine phosphorylation, we sought to identify protein tyrosine phosphatases (PTPs) regulating the invasiveness of RA FLS. We describe that the transmembrane receptor PTPκ (RPTPκ), encoded by the transforming growth factor (TGF) β-target gene, PTPRK, promotes RA FLS invasiveness

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)

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