Genomics and epidemiology of the P.1 SARS-CoV-2 lineage in Manaus, Brazil

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness

The impact of a patient’s social status on the cost of vaginal deliveries: an observational study in a French university hospital

International audienceINTRODUCTION:We aimed to assess the association between a patient's social status and the cost of stay for a single uncomplicated vaginal delivery. Currently, few data have been reported.MATERIAL AND METHODS:We conducted an observational study with data retrieved from the medical and administrative databases of a university hospital in North-West France. We included all patients admitted in 2014 and classified in either Diagnosis-Related Group (DRG) « Single uncomplicated vaginal deliveries in a primiparous patient » or DRG « Single uncomplicated vaginal deliveries in a multiparous patient ». Criteria defining poor social status were: a specific healthcare benefit in relation to low income or for foreign undocumented patients, and/or a consultation with a social worker during the hospital stay except if no social problem was diagnosed. We compared the cost of stay between patients with poor social status and patients with good social status using a multivariate median regression stratified on parity, and adjusted for age, gestational age and neonatal hospitalization.RESULTS:Among 686 primiparous patients, 21% had poor social status, which was associated with an increase in the median cost of stay (+€475; 95% CI [+334 to +616]), mostly explained by a 1-day increase in the median length of stay.Among 899 multiparous patients, 29% had poor social status, which was not associated with the cost of stay.DISCUSSION:Social status had an impact on the cost of vaginal deliveries in primiparous patients. Our findings suggest a need to redefine the DRG classification according to patients' social status

Are patients living far from hospital at higher risk of late adjuvant chemotherapy for colon cancer?

AimsLate adjuvant chemotherapy (aCT) administration after colectomy (>56 d) is known to be associated with impaired prognosis. We aim to identify risk factors associated with late aCT, especially the travel time between patients' home and hospital.MethodsWe performed a retrospective monocentre cohort study. Patients included had a colectomy for a stage III or high risk stage II colon cancer between 2009 and 2015 performed at a French university hospital. Risk factors for late aCT were identified using a fractional polynomial logistic regression.ResultsNinety-four patients were included. The risk of late aCT was associated with travel time length, emergent colectomy, the need for scheduled care before aCT, and length of time between colectomy and postoperative multidisciplinary meeting advising aCT.ConclusionOur study suggests that, in patients with colon cancer, factors unrelated to disease severity and complexity could be associated with a higher risk of late aCT

Role of periosteum during healing of alveolar critical size bone defects in the mandible: a pilot study

Minipigs present advantages for studying oral bone regeneration; however, standardized critical size defects (CSD) for alveolar bone have not been validated yet. The objectives of this study are to develop a CSD in the mandibular alveolar bone in Aachen minipigs and to further investigate the specific role of periosteum

Totally implanted venous access-associated adverse events in oncology: Results from a prospective 1-year surveillance programme

International audienceDuring the last decade, most studies on totally implanted venous access-associated adverse events (TIVA-AE) were conducted retrospectively and/or were based on a limited sample size. The aim of our survey was two-fold: to estimate the incidence of TIVA-AE and to identify risk factors in patients with cancer

Immunodynamics of explanted human tumors for immuno-oncology

International audienceDecision making in immuno-oncology is pivotal to adapt therapy to the tumor microenvironment (TME) of the patient among the numerous options of monoclonal antibodies or small molecules. Predicting the best combinatorial regimen remains an unmet medical need. Here, we report a multiplex functional and dynamic immuno-assay based on the capacity of the TME to respond to ex vivo stimulation with twelve immunomodulators including immune checkpoint inhibitors (ICI) in 43 human primary tumors. This "in sitro" (in situ/in vitro) assay has the potential to predict unresponsiveness to anti-PD-1 mAbs, and to detect the most appropriate and personalized combinatorial regimen. Prospective clinical trials are awaited to validate this in sitro assay

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