Exosomes decorated with a recombinant SARS-CoV-2 receptor-binding domain as an inhalable COVID-19 vaccine

The first two mRNA vaccines against infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that were approved by regulators require a cold chain and were designed to elicit systemic immunity via intramuscular injection. Here we report the design and preclinical testing of an inhalable virus-like-particle as a COVID-19 vaccine that, after lyophilisation, is stable at room temperature for over three months. The vaccine consists of a recombinant SARS-CoV-2 receptor-binding domain (RBD) conjugated to lung-derived exosomes which, with respect to liposomes, enhance the retention of the RBD in both the mucus-lined respiratory airway and in lung parenchyma. In mice, the vaccine elicited RBD-specific IgG antibodies, mucosal IgA responses and CD4+ and CD8+ T cells with a Th1-like cytokine expression profile in the animals’ lungs, and cleared them of SARS-CoV-2 pseudovirus after a challenge. In hamsters, two doses of the vaccine attenuated severe pneumonia and reduced inflammatory infiltrates after a challenge with live SARS-CoV-2. Inhalable and room-temperature-stable virus-like particles may become promising vaccine candidates

Outcomes of minimally invasive partial nephrectomy among very elderly patients: Report from the resurge collaborative international database

The aim of the study was to perform a comprehensive investigation of clinical outcomes of robot-assisted partial nephrectomy (RAPN) or laparoscopic partial nephrectomy (LPN) in elderly patients presenting with a renal mass.The REnal SURGery in Elderly (RESURGE) collaborative database was queried to identify patients aged 75 or older diagnosed with cT1-2 renal mass and treated with RAPN or LPN. Study outcomes were: overall complications (OC); warm ischemia time (WIT) and 6-month estimated glomerular filtration rate (eGFR); positive surgical margins (PSM), disease recurrence (REC), cancer-specific mortality (CSM) and other-cause mortality (OCM). Descriptive statistics, Kaplan-Meier, smoothed Poisson plots and logistic and linear regression models (MVA) were used.Overall, 216 patients were included in this analysis. OC rate was 34%, most of them being of low Clavien grade. Median WIT was 17 minutes and median 6-month eGFR was 54 ml/min/1.73 m(2). PSM rate was 5%. After a median follow-up of 20 months, the 5-year rates of REC, CSM and OCM were 4, 4 and 5%, respectively. At MVA predicting perioperative morbidity, RAPN relative to LPN (odds ratio [OR] 0.33; p <0.0001) was associated with lower OC rate. At MVA predicting functional outcomes, RAPN relative to LPN was associated with shorter WIT (estimate [EST]-4.09; p <0.0001), and with higher 6-month eGFR (EST 6.03; p = 0.01).In appropriately selected patients with small renal masses, minimally-invasive PN is associated with acceptable perioperative outcomes. The use of a robotic approach over a standard laparoscopic approach can be advantageous with respect to clinically relevant outcomes, and it should be preferred when available

Success with antiretroviral treatment for children in Kigali, Rwanda: Experience with health center/nurse-based care

BACKGROUND: Although a number of studies have shown good results in treating children with antiretroviral drugs (ARVs) in hospital settings, there is limited published information on results in pediatric programs that are nurse-centered and based in health centers, in particular on the psychosocial aspects of care. METHODS: Program treatment and outcome data were reported from two government-run health centers that were supported by Médecins Sans Frontières (MSF) in Kigali, Rwanda between October 2003 and June 2007. Interviews were held with health center staff and MSF program records were reviewed to describe the organization of the program. Important aspects included adequate training and supervision of nurses to manage ARV treatment. The program also emphasized family-centered care addressing the psychosocial needs of both caregivers and children to encourage early diagnosis, good adherence and follow-up. RESULTS: A total of 315 children (< 15 years) were started on ARVs, at a median age of 7.2 years (range: 0.7-14.9). Sixty percent were in WHO clinical stage I/II, with a median CD4% of 14%. Eighty-nine percent (n = 281) started a stavudine-containing regimen, mainly using the adult fixed-dose combination. The median follow-up time after ARV initiation was 2 years (interquartile range 1.2-2.6). Eighty-four percent (n = 265) of children were still on treatment in the program. Thirty (9.5%) were transferred out, eight (2.6%) died and 12 (3.8%) were lost to follow-up. An important feature of the study was that viral loads were done at a median time period of 18 months after starting ARVs and were available for 87% of the children. Of the 174 samples, VL was < 400 copies/ml in 82.8% (n = 144). Two children were started on second-line ARVs. Treatment was changed due to toxicity for 26 children (8.3%), mainly related to nevirapine. CONCLUSION: This report suggests that providing ARVs to children in a health center/nurse-based program is both feasible and very effective. Adequate numbers and training of nursing staff and an emphasis on the psychosocial needs of caregivers and children have been key elements for the successful scaling-up of ARVs at this level of the health system

The ERUS curriculum for robot-assisted partial nephrectomy: structure definition and pilot clinical validation

Background: No validated training program for robot-assisted partial nephrectomy (RAPN) exists.Objective: To define the structure and provide a pilot clinical validation of a curriculum for robot-assisted partial nephrectomy (RAPN).Design, setting, and participants: A modified Delphi consensus methodology involving 27 experts defined curriculum structure. One trainee completed the curriculum under the mentorship of an expert. A total of 40 patients treated with curriculum RAPN (cRAPN) were compared with 160 patients treated with standard of care (sRAPN).Outcome measurements and statistical analysis: To define curriculum structure, consensus was defined as >= 90% expert agreement. To investigate curriculum safety, perioperative morbidity, renal function, and pathologic outcomes were evaluated. To investigate curriculum efficacy, RAPN steps and modules attempted and completed by the trainee were evaluated. Propensity score matching identified comparable cRAPN and sRAPN cases. Mann-Whitney U test, chi-square test, and linear regression were used to investigate the impact of the curriculum on patient's outcome and the impact of trainee's experience on surgical independence.Results and limitations: Consensus-based key statements defined curriculum structure. No difference was recorded between cRAPN and sRAPN with respect to intraoperative or overall and grade-specific postoperative complications, blood loss, ischemia time, postoperative estimated glomerular filtration rate, and positive surgical margins (all p > 0.05). Conversely, operative time was longer after cRAPN (p < 0.0001). The trainee completed all phases of the curriculum and the trainee's experience was associated with more steps attempted/completed and increasing complexity of module attempted/completed (all p < 0.0001). The limitations of the study are the enrolment of a single trainee at a single institution and the small sample size. Accordingly, the large confidence intervals observed cannot exclude inferior outcomes in case of cRAPN and further study is required to confirm safety.Conclusions: The European Association of Urology (EAU) Robotic Urology Section (ERUS) curriculum for RAPN can protect patients from suboptimal outcome during the learning curve of the surgeon and can aid surgeons willing to start an RAPN program.Patient summary: Patients should be aware that structured training programs can reduce the risk of suboptimal outcome due to the learning curve of the surgeon. (C) 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.</p

Estrogenic activity of a polyphenolic extract of the leaves of Epimedium brevicornum

The estrogenic activity of a polyphenolic extract of the leaves of Epimedium brevicornum and five fractions obtained by solid-phase extraction were investigated using estrogen-responsive bioassays, a yeast cell assay and the Ishikawa Var-I assay. The extract was found to exhibit significant estrogenic activity in both assays. Furthermore, bioassay-guided fractionation led to localisation of the estrogenicity in the relatively non-polar fractions of the polyphenolic extract. (C) 2004 Elsevier B.V. All rights reserved