Cancer du sein traité par chimiothérapie néo-adjuvante, chirurgie conservatrice et radiothérapie (facteurs pronostiques de rechute locorégionale)

Objectifs : l objectif principal est l étude des facteurs pronostiques de rechute locorégionale. L objectif secondaire est l étude du rôle et des indications de la radiothérapie après chimiothérapie néo-adjuvante et traitement chirurgical conservateur. Matériels et méthodes : Analyse rétrospective de 290 patientes prises en charge, de 1990 à 2004, à l Institut Bergonié à Bordeaux, pour un cancer du sein non métastatique traité par une chimiothérapie première suivie d un traitement chirurgical conservateur et d une radiothérapie. Etude des taux de rechute locorégionale en fonction de plusieurs facteurs pronostiques potentiels. Résultats : L analyse univariée a permis d identifier cinq facteurs pronostiques de rechute locorégionale, statistiquement significatifs : l âge au diagnostique inférieur à 40 ans (p = 5.69x10-5), la négativité des récepteurs hormonaux (p = 0.0001), l envahissement ganglionnaire clinique initial (p = 0.006), l envahissement ganglionnaire au curage axillaire, après chimiothérapie (p 0.0008), la présence de carcinome canalaire in situ dans la pièce opératoire (p = 0.0006). En analyse multivariée, trois de ces facteurs sont indépendants : la négativité des récepteurs hormonaux (RR = 4.015 IC 95% [2.057-7.837], l âge initial inférieur à 40 ans (RR = 2.801 IC 95% [1.592-4.926]), et l envahissement ganglionnaire au curage axillaire (RR = 2.302 IC 95% [1.248-4.246]). Conclusion. Dans notre série, la négativité des récepteurs hormonaux, l âge inférieur à 40 ans et l envahissement ganglionnaire au curage axillaire sont des facteurs pronostiques de rechute locorégionale après chimiothérapie première et chirurgie conservatrice. Cela soulève la question de la prise en charge thérapeutique optimale pour ces patientes à haut risque : faut-il proposer une mastectomie, ou peut-on intensifier le traitement locorégional et notamment la radiothérapie afin de limiter ce risque de rechute ?BORDEAUX2-BU Santé (330632101) / SudocFORT-DE-FRANCE-CHRU-BU (972332102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Lifting Dyspnoea Invisibility: COVID-19 Face Masks, the Experience of Breathing Discomfort, and Improved Lung Health Perception \textendash a French Nationwide Survey

Question addressed In contrast with pain, dyspnoea is not visible to the general public, who lack the corresponding experiential baggage. We tested the hypothesis that the generalised use of face masks to fight severe acute respiratory syndrome coronavirus 2 dissemination could change this and sensitise people to respiratory health. Methods General population polling (1012-person panel demographically representative of the adult French population, quota sampling method; 517 (51%) female). 860 (85%) answered ``no'' to ``treated for a chronic respiratory disease'' (``respiratory healthy''), and 152 answered ``yes'' (``respiratory disease''). 14% of respiratory healthy respondents reported having a close family member treated for a chronic respiratory disease (RH-family + ). Respondents described mask-related attitudes, beliefs, inconveniencies, dyspnoea and changes in their respiratory health vision . Results Compliance with masks was high (94.7%). Dyspnoea ranked first among mask inconveniencies (respiratory disease 79.3%, respiratory healthy 67.3%; p=0.013). ``Air hunger'' was the main sensory dyspnoea descriptor. Mask-related dyspnoea was independently associated with belonging to RH-family + (OR 1.85, 95% CI 1.16\textendash 2.98) and removing masks to improve breathing (OR 5.21, 95% CI 3.73\textendash 7.28). It was negatively associated with considering masks effective to protect others (OR 0.42, 95% CI 0.25\textendash 0.75). Half the respondents were more concerned with their respiratory health since wearing masks; 41% reported better understanding patients' experiences. Answer to the question Wearing protective face masks leads to the mass discovery of breathing discomfort. It raises public awareness of what respiratory diseases involve and sensitivity to the importance of breathing. These data should be used as the fulcrum of respiratory health oriented communication actions

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Correction: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

International audienc

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population