High seroprevalence but short-lived immune response to SARS-CoV-2 infection in Paris.

Although the COVID-19 pandemic peaked in March/April 2020 in France, the prevalence of infection is barely known. Using high-throughput methods, we assessed herein the serological response against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) of 1847 participants working in three sites of an institution in Paris conurbation. In May-July 2020, 11% (95% confidence interval [CI]: 9.7-12.6) of serums were positive for IgG against the SARS-CoV-2 N and S proteins, and 9.5% (95% CI: 8.2-11.0) were neutralizer in pseudo-typed virus assays. The prevalence of seroconversion was 11.6% (95% CI: 10.2-13.2) when considering positivity in at least one assay. In 5% of RT-qPCR positive individuals, no systemic IgGs were detected. Among immune individuals, 21% had been asymptomatic. Anosmia (loss of smell) and ageusia (loss of taste) occurred in 52% of the IgG-positive individuals and in 3% of the negative ones. In contrast, 30% of the anosmia-ageusia cases were seronegative, suggesting that the true prevalence of infection may have reached 16.6%. In sera obtained 4-8 weeks after the first sampling, anti-N and anti-S IgG titers and neutralization activity in pseudo-virus assay declined by 31%, 17%, and 53%, resulting thus in half-life of 35, 87, and 28 days, respectively. The population studied is representative of active workers in Paris. The short lifespan of the serological systemic responses suggests an underestimation of the true prevalence of infection.

Validation of a high performance functional assay for individual radiosensitivity in pediatric oncology: a prospective cohort study (ARPEGE).

BACKGROUND: Approximately 900 children/adolescents are treated with radiotherapy (RT) every year in France. However, among the 80% of survivors, the cumulative incidence of long-term morbidity - including second malignancies - reach 73.4% thirty years after the cancer diagnosis. Identifying a priori the subjects at risk for RT sequelae is a major challenge of paediatric oncology. Individual radiosensitivity (IRS) of children/adolescents is unknown at this time, probably with large variability depending on the age when considering the changes in metabolic functions throughout growth. We previously retrospectively showed that unrepaired DNA double strand breaks (DSB) as well a delay in the nucleoshuttling of the pATM protein were common features to patients with RT toxicity. We aim to validate a high performance functional assay for IRS prospectively. METHODS/DESIGN: ARPEGE is a prospective open-label, non-randomized multicentre cohort study. We will prospectively recruit 222 children/adolescents who require RT as part of their routine care and follow them during 15 years. Prior RT we will collect blood and skin samples to raise a primary dermal fibroblast line to carry out in blind the IRS assay. As a primary objective, we will determine its discriminating ability to predict the occurrence of unusual early skin, mucous or hematological toxicity. The primary endpoint is the measurement of residual double-strand breaks 24 h after ex vivo radiation assessed with indirect immunofluorescence (γH2AX marker). Secondary endpoints include the determination of pATM foci at 10 min and 1 h (pATM marker) and micronuclei at 24 h. In parallel toxicity including second malignancies will be reported according to NCI-CTCAE v4.0 reference scale three months of the completion of RT then periodically during 15 years. Confusion factors such as irradiated volume, skin phototype, previous chemotherapy regimen, smoking, comorbities (diabetes, immunodeficiency, chronic inflammatory disease...) will be reported. DISCUSSION: ARPEGE would be the first study to document the distribution of IRS in the pediatric subpopulation. Screening hypersensitive patients would be a major step forward in the management of cancers, opening a way to personalized pediatric oncology. TRIAL REGISTRATION: ID-RCB number: 2015-A00975-44, ClinicalTrials.gov Identifier: NCT02827552 Registered 7/6/2016.

Application of Machine Learning Prediction of Individual SARS-CoV-2 Vaccination and Infection Status to the French Serosurveillance Survey From March 2020 to 2022: Cross-Sectional Study.

BACKGROUND: The seroprevalence of SARS-CoV-2 infection in the French population was estimated with a representative, repeated cross-sectional survey based on residual sera from routine blood testing. These data contained no information on infection or vaccination status, thus limiting the ability to detail changes observed in the immunity level of the population over time. OBJECTIVE: Our aim is to predict the infected or vaccinated status of individuals in the French serosurveillance survey based only on the results of serological assays. Reference data on longitudinal serological profiles of seronegative, infected, and vaccinated individuals from another French cohort were used to build the predictive model. METHODS: A model of individual vaccination or infection status with respect to SARS-CoV-2 obtained from a machine learning procedure was proposed based on 3 complementary serological assays. This model was applied to the French nationwide serosurveillance survey from March 2020 to March 2022 to estimate the proportions of the population that were negative, infected, vaccinated, or infected and vaccinated. RESULTS: From February 2021 to March 2022, the estimated percentage of infected and unvaccinated individuals in France increased from 7.5% to 16.8%. During this period, the estimated percentage increased from 3.6% to 45.2% for vaccinated and uninfected individuals and from 2.1% to 29.1% for vaccinated and infected individuals. The decrease in the seronegative population can be largely attributed to vaccination. CONCLUSIONS: Combining results from the serosurveillance survey with more complete data from another longitudinal cohort completes the information retrieved from serosurveillance while keeping its protocol simple and easy to implement.

Self-compression Technique vs Standard Compression in Mammography: A Randomized Clinical Trial.

Importance: Many women dread undergoing mammography, and some may not attend or reattend breast cancer screening because of the discomfort or pain induced by breast compression. Objective: To evaluate the noninferiority of the self-compression mammography technique for reducing breast thickness compared with standard compression. Design, Setting, and Participants: This prospective, parallel-group, noninferiority randomized clinical trial was conducted from May 7, 2013, to October 26, 2015, at 6 cancer care centers in France. Participants were women aged 50 to 75 years, without a history of recent breast surgical procedure or treatment, and who could perform self-compression. Analyses were performed on intention-to-treat basis from January 27, 2017, to March 30, 2018. Interventions: Patients were randomized 1:1 to the self-compression group or the standard compression group. Main Outcomes and Measures: Primary end point was breast thickness expressed as the mean of 4 views: right and left craniocaudal and right and left mediolateral oblique. The predefined noninferiority margin was a difference of 3 mm, with a 1-sided 95% CI. Secondary end points included compression force, image quality, requirement for additional views, pain, and patient satisfaction and radiographer assessment questionnaires. Results: Among the 549 women randomized, 548 (97.3%) completed the trial. Of these, 275 (48.8%) (mean [SD] age, 61.35 [6.34] years) were randomized to the self-compression arm and 273 (48.5%) (mean [SD] age, 60.84 [6.41] years) to the standard compression arm. The difference in the mean thickness between the 2 arms was lower than the noninferiority margin, with an upper 1-sided 95% CI less than 3 mm (-0.17; 95% CI,-∞ to 1.89 mm; P < .05). Compression force was higher in the self-compression group compared with the standard compression arm for the 4 mammographic views. Pain was statistically significantly lower in the self-compression group (n = 274) compared with the standard compression group (n = 269) (median [interquartile range (IQR)] score, 2 [1-5] vs 3 [1-5]; P = .009). No difference was reported in the image quality scores of the 2 groups or in the number of additional views performed (median [IQR] extra views, 2 [2-2] vs 2 [2-3] extra views; P = .64), whatever the indication, including insufficient image quality (29 [16.8%] vs 27 [15.0%] insufficient quality views; P = .65). No adverse effects or pain were reported by the participants after the self-compression mammography. Conclusions and Relevance: Self-compression does not appear to be inferior to standard compression mammography in achieving minimal breast thickness without increasing pain or compromising image quality; this technique may be an effective option for women who want to be involved in their breast examination. Trial Registration: ClinicalTrials.gov identifier: NCT02866591.

Anticancer Drug Delivery: An Update on Clinically Applied Nanotherapeutics.

The development of chemotherapy using conventional anticancer drugs has been hindered due to several drawbacks related to their poor water solubility and poor pharmacokinetics, leading to severe adverse side effects and multidrug resistance in patients. Nanocarriers were developed to palliate these problems by improving drug delivery, opening the era of nanomedicine in oncology. Liposomes have been by far the most used nanovectors for drug delivery, with liposomal doxorubicin receiving US FDA approval as early as 1995. Antibody drug conjugates and promising drug delivery systems based on a natural polymer, such as albumin, or a synthetic polymer, are currently undergoing advanced clinical trials or have received approval for clinical applications. However, despite attractive results being obtained in preclinical studies, many well-designed nanodrugs fell short of expectations when tested in patients, evidencing the gap between nanoparticle design and their clinical translation. The aim of this review is to evaluate the extent of nanotherapeutics used in oncology by providing an insight into the most successful concepts. The reasons that prevent nanodrugs from expanding to clinic are discussed, and the efforts that must be taken to take full advantage of the great potential of nanomedicine are highlighted.

[Salvage surgery for upper aerodigestive tract tumours]. / Chirurgie de rattrapage dans les tumeurs des VADS.

Salvage surgeries of head and neck tumors are considered as poor satisfactory either for disease control results or for aesthetic and functional outcomes. Several improvements have been made possible since few years in all fields of oncologic treatments. A new approach must be initiated in that context, moreover since take in charge for head and neck region (exclusive initial medical treatment) let us consider an increasement of clinical situations for which a salvage therapy could be performed. The new surgery techniques have to be considered, reconstructive and guided by systems, which can improve surgical skills (navigation, robotic, sentinel node procedure, nervous detection and so on), the help of reirradiation techniques, the use of medical therapy during surgical procedure, the photodynamic therapy and all the help provided by new medical imaging and modern biology, which can determine more precisely the status of the cancer when it is taken in charge. The mastery of those techniques improvements must follow on an evolution of the concepts in the field of combined salvage treatments performed by multidisciplinary teams. Those treatments have to be realized in structures, which have the techniques and the multiple skills for allowing increasement of outcomes of those severe diseases.