Acceptation de la vaccination SARS-CoV-2 par les femmes enceintes et allaitantes lors de la première vague de pandémie : Une étude transversale suisse

Alors que plusieurs études ont montré que les femmes enceintes représentent une population à risque de contamination par le SARS-CoV-2 et que la vaccination est maintenant disponible en Suisse, ce travail de thèse s’intéresse au taux d’acceptation du vaccin SARS-CoV-2 parmi les femmes enceintes et allaitantes suisses, ainsi qu’aux différents facteurs influençant le choix ou non de se faire vacciner. Les données concernant l’acceptation de la vaccination chez les femmes enceintes et allaitantes suisses, ainsi que les différents facteurs influençant cette décision, sont extraites d’une étude européenne multi-centrique conduite dans plusieurs pays (Suisse, Belgique, Irlande, Norvège, Pays- Bas et Angleterre) sous forme de questionnaire en ligne, accessible du 18.06.2020 au 12.07.2020 sur différents sites web, forums et médias sociaux. Cette étude, publiée en février 2021, a investigué l’impact global que la première vague de pandémie SARS-CoV-2 a eu sur les femmes enceintes et allaitantes, notamment sur leur expérience de grossesse ou allaitement, sur leur quotidien personnel et professionnel, leur santé psychique, leur relation avec les soignants, l’utilisation de médicaments ainsi que l’impact sur leur position face à la vaccination durant la grossesse ou l’allaitement. Ce travail de thèse montre que seul un tiers des femmes interrogées accepteraient de se faire vacciner contre le SARS-CoV-2, chiffre particulièrement bas en comparaison avec des études similaires menées dans d'autres pays. Il identifie différents facteurs contribuant à l'acceptation ou au refus d'une telle vaccination chez les femmes enceintes et allaitantes suisses et montre que ces éléments n'influençent pas uniquement la volonté de se faire vacciner contre le SARS-CoV-2, mais qu'ils concernent la majorité des autres vaccins préconisés pendant la grossesse ou l'allaitement. Ainsi, les patientes jeunes, étant en situation de précarité, ou avec un niveau d'éducation plus bas seraient plus réticentes à se faire vacciner. Les patientes résidant en Suisse Alémanique, moins touchée par la première vague, étaient également plus réticentes à la vaccination. Ce travail souligne l’importance d’identifier les barrières à la vaccination pendant la grossesse et l'allaitement pour optimiser la prise en charge et la protection des mères et de leurs enfants contre les virus passés, présents et futurs. -- As pregnant women are at high risk of severe SARS-CoV-2 infection and COVID-19 vac- cines are available in Switzerland, this study aimed to assess the willingness of Swiss pregnant and breastfeeding women to become vaccinated. Through a cross-sectional online study conducted after the first pandemic wave, vaccination practices and willingness to become vaccinated against SARS- CoV-2 if a vaccine was available were evaluated through binary, multi-choice, and open-ended questions. Factors associated with vaccine willingness were evaluated through univariable and multivariable analysis. A total of 1551 women responded to questions related to the primary out- come. Only 29.7% (153/515) of pregnant and 38.6% (400/1036) of breastfeeding women were willing to get vaccinated against SARS-CoV-2 if a vaccine had been available during the first wave. Positive predictors associated with SARS-CoV-2 vaccine acceptance were an age older than 40 years, a higher educational level, history of influenza vaccination within the previous year, having an obstetrician as the primary healthcare practitioner, and being in their third trimester of pregnancy. After the first pandemic wave, Switzerland had a low SARS-CoV-2 vaccination acceptance rate, emphasizing the need to identify and reduce barriers for immunization in pregnant and breastfeeding women, par- ticularly among the youngest and those with a lower educational level

SARS-CoV-2 Vaccine Willingness among Pregnant and Breastfeeding Women during the First Pandemic Wave: A Cross-Sectional Study in Switzerland.

As pregnant women are at high risk of severe SARS-CoV-2 infection and COVID-19 vaccines are available in Switzerland, this study aimed to assess the willingness of Swiss pregnant and breastfeeding women to become vaccinated. Through a cross-sectional online study conducted after the first pandemic wave, vaccination practices and willingness to become vaccinated against SARS-CoV-2 if a vaccine was available were evaluated through binary, multi-choice, and open-ended questions. Factors associated with vaccine willingness were evaluated through univariable and multivariable analysis. A total of 1551 women responded to questions related to the primary outcome. Only 29.7% (153/515) of pregnant and 38.6% (400/1036) of breastfeeding women were willing to get vaccinated against SARS-CoV-2 if a vaccine had been available during the first wave. Positive predictors associated with SARS-CoV-2 vaccine acceptance were an age older than 40 years, a higher educational level, history of influenza vaccination within the previous year, having an obstetrician as the primary healthcare practitioner, and being in their third trimester of pregnancy. After the first pandemic wave, Switzerland had a low SARS-CoV-2 vaccination acceptance rate, emphasizing the need to identify and reduce barriers for immunization in pregnant and breastfeeding women, particularly among the youngest and those with a lower educational level

Primordial germ cells as a potential shared cell of origin for mucinous cystic neoplasms of the pancreas and mucinous ovarian tumors

Mucinous ovarian tumors (MOTs) morphologically and epidemiologically resemble mucinous cystic neoplasms (MCNs) of the pancreas, sharing a similar stroma and both occurring disproportionately among young females. Additionally, MOTs and MCNs share similar clinical characteristics and immunohistochemical phenotypes. Exome sequencing has revealed frequent recurrent mutations in KRAS and RNF43 in both MOTs and MCNs. The cell of origin for these tumors remains unclear, but MOTs sometimes arise in the context of mature cystic teratomas and other primordial germ cell (PGC) tumors. We undertook the present study to investigate whether non-teratoma-associated MOTs and MCNs share a common cell of origin. Comparisons of the gene expression profiles of MOTs [including both the mucinous borderline ovarian tumors (MBOTs) and invasive mucinous ovarian carcinomas (MOCs)], high-grade serous ovarian carcinomas, ovarian surface epithelium, Fallopian tube epithelium, normal pancreatic tissue, pancreatic duct adenocarcinomas, MCNs, and single-cell RNA-sequencing of PGCs revealed that both MOTs and MCNs are more closely related to PGCs than to either eutopic epithelial tumors or normal epithelia. We hypothesize that MCNs may arise from PGCs that stopped in the dorsal pancreas during their descent to the gonads during early human embryogenesis, while MOTs arise from PGCs in the ovary. Together, these data suggest a common pathway for the development of MCNs and MOTs, and suggest that these tumors may be more properly classified as germ cell tumor variants

Intra-Tumoral Nerve-Tracing in a Novel Syngeneic Model of High-Grade Serous Ovarian Carcinoma

Dense tumor innervation is associated with enhanced cancer progression and poor prognosis. We observed innervation in breast, prostate, pancreatic, lung, liver, ovarian, and colon cancers. Defining innervation in high-grade serous ovarian carcinoma (HGSOC) was a focus since sensory innervation was observed whereas the normal tissue contains predominantly sympathetic input. The origin, specific nerve type, and the mechanisms promoting innervation and driving nerve-cancer cell communications in ovarian cancer remain largely unknown. The technique of neuro-tracing enhances the study of tumor innervation by offering a means for identification and mapping of nerve sources that may directly and indirectly affect the tumor microenvironment. Here, we establish a murine model of HGSOC and utilize image-guided microinjections of retrograde neuro-tracer to label tumor-infiltrating peripheral neurons, mapping their source and circuitry. We show that regional sensory neurons innervate HGSOC tumors. Interestingly, the axons within the tumor trace back to local dorsal root ganglia as well as jugular–nodose ganglia. Further manipulations of these tumor projecting neurons may define the neuronal contributions in tumor growth, invasion, metastasis, and responses to therapeutics

Location of Mutation in BRCA2 Gene and Survival in Patients with Ovarian Cancer

Purpose: BRCA2 plays a central role in homologous recombination by loading RAD51 on DNA breaks. The objective of this study is to determine whether the location of mutations in the RAD51-binding domain (RAD51-BD; exon 11) of BRCA2 gene affects the clinical outcome of ovarian cancer patients.Experimental Design: A study cohort of 353 women with ovarian cancer who underwent genetic germline testing for BRCA1 and BRCA2 genes was identified. Progression-free survival (PFS), platinum-free interval (PFI), and overall survival (OS) were analyzed. The Cancer Genome Atlas (TCGA) cohort of ovarian cancer (n = 316) was used as a validation cohort.Results: In the study cohort, 78 patients were carriers of germline mutations of BRCA2 After adjustment for FIGO stage and macroscopic residual disease, BRCA2 carriers with truncating mutations in the RAD51-BD have significantly prolonged 5-year PFS [58%; adjusted HR, 0.36; 95% confidence interval (CI), 0.20-0.64; P = 0.001] and prolonged PFI (29.7 vs. 15.5 months, P = 0.011), compared with noncarriers. BRCA2 carriers with mutations located in other domains of the gene do not have prolonged 5-year PFS (28%, adjusted HR, 0.67; 95% CI, 0.42-1.07; P = 0.094) or PFI (19 vs. 15.5 months, P = 0.146). In the TCGA cohort, only BRCA2 carriers harboring germline or somatic mutations in the RAD51-BD have prolonged 5-year PFS (46%; adjusted HR, 0.30; 95% CI, 0.13-0.68; P = 0.004) and 5-year OS (78%; adjusted HR, 0.09; 95% CI, 0.02-0.38; P = 0.001).Conclusions: Among ovarian cancer patients, BRCA2 carriers with mutations located in the RAD51-BD (exon 11) have prolonged PFS, PFI, and OS. Clin Cancer Res; 24(2); 326-33. ©2017 AACR