[Impact of precariousness on breast cancer care in the Île-de-France region: Results of the DESSEIN study]. / Impact de la précarité sur la prise en charge du cancer du sein en Île-de-France : résultats de l'étude DESSEIN.

INTRODUCTION: Precariousness has been associated with an increase in breast cancer mortality, but the links between precariousness, stage at diagnosis and care pathways are little explored. The objective of the DESSEIN study was to assess the impact of precariousness on disease and care pathways. METHODS: Prospective observational study in Île-de-France comparing precarious and non-precarious patients consulting for breast cancer and followed for 1 year. RESULTS: In total, 875 patients were included between 2016 and 2019 in 19 institutions: 543 non-precarious patients and 332 precarious patients. Precarious patients had a more advanced stage at diagnosis (55% T1 vs. 63%, 30% N+ vs 19%, P=0.0006), had a higher risk of not receiving initially planned treatment (4 vs. 1%, P=0.004), and participated less in clinical trials (5 vs. 9%, P=0.03). Non-use of supportive oncology care was 2 times more frequent among patients in precarious situations (P<0.001). During treatment, 33% of deprived patients reported a loss of income, compared with 24% of non-deprived patients (P<0.001). At 12 months from diagnosis, lay-offs were 2 times more frequent in precarious patients (P=0.0001). DISCUSSION: Precariousness affects all stages of the cancer history and care pathway. Particular attention needs to be paid to vulnerable populations, considering issues of accessibility and affordability of care, health literacy and possible implicit bias from the care providers.

Suture versus open mesh repair for small umbilical hernia: Results of a propensity-matched cohort study.

BACKGROUND: The objective was to compare the outcomes of open mesh repair versus suture repair for small (≤1 cm in diameter) umbilical hernia. The primary endpoint was the 30-day outcomes including pain, and secondary endpoints were the 2-year outcomes including recurrences and patient-reported outcomes. METHODS: This propensity-matched, multicenter study was carried out on data collected prospectively in the Hernia-Club database between 2011 and 2021. A total of 590 mesh repairs and 590 suture repairs were propensity score matched (age, sex, body mass index) at a ratio of 1:1. Postoperative pain was assessed using the Verbal Rating Scale-4 and 0‒10 Numerical Rating Scale-11. RESULTS: Mesh insertion was intraperitoneal in 331 patients (56.1%), extraperitoneal in 249 (42.2%), and onlay in 10 (1.7%). The rate of 30-day complications and Numerical Rating Scale-11 pain scores on postoperative days 8 and 30 were similar between the groups, including surgical site occurrences (2.2 vs 1.4% after suture repair). At 1 month, postoperative discomfort (sensation of something different from before) was significantly (P < .0001) more frequent after mesh repair, whereas the rate of relevant (moderate or severe) pain (mesh repair: 1.1% vs suture repair: 2.6%) and the distribution of Numerical Rating Scale-11 scores did not differ between the groups. At the 2-year follow-up, mesh repair patients had fewer reoperated recurrences (0.2% vs 1.7%; P = .035) and no more pain or discomfort than suture repair patients. CONCLUSION: Both techniques are effective and safe. Mesh repair is likely to reduce the rate of recurrences. Concerns about postoperative pain and infection might not prevent the use of mesh in smallest umbilical hernias.

Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza.

Recent approval of mRNA vaccines for emergency use against COVID-19 is likely to promote rapid development of mRNA-based vaccines targeting a wide range of infectious diseases. Compared to conventional approaches, this vaccine modality promises comparable potency while substantially accelerating the pace of development and deployment of vaccine doses. Already demonstrated successfully for single antigen vaccines such as for COVID-19, this technology could be optimized for complex multi-antigen vaccines. Herein, utilizing multiple influenza antigens, we demonstrated the suitability of the mRNA therapeutic (MRT) platform for such applications. Seasonal influenza vaccines have three or four hemagglutinin (HA) antigens of different viral subtypes. In addition, influenza neuraminidase (NA), a tetrameric membrane protein, is identified as an antigen that has been linked to protective immunity against severe viral disease. We detail the efforts in optimizing formulations of influenza candidates that use unmodified mRNA encoding full-length HA or full-length NA encapsulated in lipid nanoparticles (LNPs). HA and NA mRNA-LNP formulations, either as monovalent or as multivalent vaccines, induced strong functional antibody and cellular responses in non-human primates and such antigen-specific antibody responses were associated with protective efficacy against viral challenge in mice.

Immunogenicity and efficacy of mRNA COVID-19 vaccine MRT5500 in preclinical animal models.

Emergency use authorization of COVID vaccines has brought hope to mitigate pandemic of coronavirus disease 2019 (COVID-19). However, there remains a need for additional effective vaccines to meet the global demand and address the potential new viral variants. mRNA technologies offer an expeditious path alternative to traditional vaccine approaches. Here we describe the efforts to utilize an mRNA platform for rational design and evaluations of mRNA vaccine candidates based on the spike (S) glycoprotein of SARS-CoV-2. Several mRNA constructs of S-protein, including wild type, a pre-fusion stabilized mutant (2P), a furin cleavage-site mutant (GSAS) and a double mutant form (2P/GSAS), as well as others, were tested in animal models for their capacity to elicit neutralizing antibodies (nAbs). The lead 2P/GSAS candidate was further assessed in dose-ranging studies in mice and Cynomolgus macaques, and for efficacy in a Syrian golden hamster model. The selected 2P/GSAS vaccine formulation, designated MRT5500, elicited potent nAbs as measured in neutralization assays in all three preclinical models and more importantly, protected against SARS-CoV-2-induced weight loss and lung pathology in hamsters. In addition, MRT5500 elicited TH1-biased responses in both mouse and non-human primate (NHP), thus alleviating a hypothetical concern of potential vaccine-associated enhanced respiratory diseases known associated with TH2-biased responses. These data position MRT5500 as a viable vaccine candidate for entering clinical development.

A Prospective, Observational Study of Conversion From Immediate- to Prolonged-Release Tacrolimus in Renal Transplant Recipients in France: The OPALE Study.

BACKGROUND Potential benefits of once-daily, prolonged-release tacrolimus over the immediate-release formulation include improved adherence to immunosuppressives post transplantation. An observational study was performed to characterize real-world practice surrounding conversion from immediate- to prolonged-release tacrolimus in kidney transplant recipients. MATERIAL AND METHODS We performed a prospective, observational study of renal transplant recipients converted from immediate- to prolonged-release tacrolimus capsules. Conversion took place at the baseline visit, within the first 6 months of transplantation (early conversion group) or between 6 and 12 months of transplantation (late conversion group). Data collection was performed at routine follow-up at 6 and 12 months. Endpoints included conversion ratio from immediate- to prolonged-release tacrolimus, reasons for conversion, additional visits due to conversion, safety, and tolerability. RESULTS The analysis population comprised 591 patients. Baseline characteristics were similar between the 2 groups. The mean conversion ratio of the daily dose of tacrolimus was 0.98±0.17 in the early group and 0.99±0.09 in the late group. Time from conversion (mean ±SD) to first measurement of trough tacrolimus blood concentration was 12.1±11.6 and 27.6±26.7 days in the early and late groups, respectively. The highest number of additional visits required was 6 in the early conversion group, in 3 patients (0.7%), and 3 in the late conversion group, in 2 patients (1.6%). Conversion from immediate- to prolonged-release tacrolimus was associated with a very low rate of graft rejection. CONCLUSIONS Favorable clinical outcomes and safety profiles were observed with conversion from immediate- to prolonged-release tacrolimus over 1 year following renal transplantation, with no marked differences between the early and late conversion groups.