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Streptococcus equi subspecies zooepidemicus is a P-hemolytic streptococcus expressing Lancefield group C antigen and is 1 of 3 S. equi subspecies. S. equi subsp. zooepidemicus is an opportunistic pathogen that [...]

Objective:Mammographic screening and management of breast cancer (BC) in elderly women are controversial and continue to be an important health problem. To investigate, through members of the Senologic International Society (SIS), the current global practices in BC in elderly women, highlighting topics of debate and suggesting perspectives.Materials and Methods:The questionnaire was sent to the SIS network and included 55 questions on definitions of an elderly woman, BC epidemiology, screening, clinical and pathological characteristics, therapeutic management in elderly women, onco-geriatric assessment and perspectives.Results:Twenty-eight respondents from 21 countries and six continents, representing a population of 2.86 billion, completed and submitted the survey. Most respondents considered women 70 years and older to be elderly. In most countries, BC was often diagnosed at an advanced stage compared to younger women, and age-related mortality was high. For this reason, participants recommended that personalized screening be continued in elderly women with a long life expectancy.In addition, this survey highlighted that geriatric frailty assessment tools and comprehensive geriatric evaluations needed to be used more and should be developed to avoid undertreatment. Similarly, multidisciplinary meetings dedicated to elderly women with BC should be encouraged to avoid under- and over-treatment and to increase their participation in clinical trials.Conclusion:Due to increased life expectancy, BC in elderly women will become a more important field in public health. Therefore, screening, personalized treatment, and comprehensive geriatric assessment should be the cornerstones of future practice to avoid the current excess of age-related mortality. This survey described, through members of the SIS, a global picture of current international practices in BC in elderly women.

Abstract Chimeric antigen receptor T (CAR-T) cell therapy may achieve long-lasting remission in patients with B-cell malignancies not responding to conventional therapies. However, potentially severe and hard-to-manage side effects, including cytokine release syndrome (CRS), neurotoxicity and macrophage activation syndrome, and the lack of pathophysiological experimental models limit the applicability and development of this form of therapy. Here we present a comprehensive humanized mouse model, by which we show that IFNγ neutralization by the clinically approved monoclonal antibody, emapalumab, mitigates severe toxicity related to CAR-T cell therapy. We demonstrate that emapalumab reduces the pro-inflammatory environment in the model, thus allowing control of severe CRS and preventing brain damage, characterized by multifocal hemorrhages. Importantly, our in vitro and in vivo experiments show that IFNγ inhibition does not affect the ability of CD19-targeting CAR-T (CAR.CD19-T) cells to eradicate CD19+ lymphoma cells. Thus, our study provides evidence that anti-IFNγ treatment might reduce immune related adverse effect without compromising therapeutic success and provides rationale for an emapalumab-CAR.CD19-T cell combination therapy in humans.

Abstract Objective In Alzheimer's disease (AD), the presence of circadian dysfunction is well‐known and may occur early in the disease course. The melanopsin retinal ganglion cell (mRGC) system may play a relevant role in contributing to circadian dysfunction. In this study, we aimed at evaluating, through a multimodal approach, the mRGC system in AD at an early stage of disease. Methods We included 29 mild–moderate AD (70.9 ± 11 years) and 26 (70.5 ± 8 years) control subjects. We performed an extensive neurophtalmological evaluation including optical coherence tomography with ganglion cell layer segmentation, actigraphic evaluation of the rest‐activity rhythm, chromatic pupillometry analyzed with a new data‐fitting approach, and brain functional MRI combined with light stimuli assessing the mRGC system. Results We demonstrated a significant thinning of the infero‐temporal sector of the ganglion cell layer in AD compared to controls. Moreover, we documented by actigraphy the presence of a circadian‐impaired AD subgroup. Overall, circadian measurements worsened by age. Chromatic pupillometry evaluation highlighted the presence of a pupil‐light response reduction in the rod condition pointing to mRGC dendropathy. Finally, brain fMRI showed a reduced occipital cortex activation with blue light particularly for the sustained responses. Interpretation Overall, the results of this multimodal innovative approach clearly document a dysfunctional mRGC system at early stages of disease as a relevant contributing factor for circadian impairment in AD providing also support to the use of light therapy in AD.

Abstract Introduction To investigate whether the quarantine periods due to the COVID‐19 pandemic were associated with excessive gestational weight gain. Methods This single‐centre retrospective observational French cohort study studied 23 774 pregnant women from 2017 to 2020 who had an obstetrical follow‐up consultation with a weight measurement in Strasbourg University Hospitals. We defined four time periods according to the two quarantine periods in France: (1) prequarantine, (2) first quarantine (all‐day curfew); (3) between quarantines, and (4) second quarantine (all‐day curfew). Inferential analyses and models were conducted using Bayesian methods. Results We developed three Bayesian models to explore the impact of quarantines on GWG. Mean GWG was 8.3 kg (standard deviation 5.0 kg) for a mean gestational age at consultation of 28.5 weeks. Compared to the same calendar periods from 2017 to 2019, the probabilities of a clinically significant increase in GWG (≥1 kg) during the different quarantine periods were extremely low (