Auditive direct in utero observation (Audio): A randomized controlled trial for a prenatal demonstration of fetal hearing

Introduction: The objective of this randomized controlled study was to demonstrate whether acoustic stimulation in utero is associated with fetal reactivity which is documentable by car-diotocography. Materials and methods: A monocentric randomized controlled trial was performed at a single university tertiary hospital between September 2016 and July 2017. This study was registered as a randomized clinical trial on clinicaltrail.gov (registration number NCT04622059). Unselected pregnancies at term of gestation were consecutively recruited for the purpose of this study. After 10 min of normal cardiotocography without accelerations (non-stress-test with a basal frequency between 110 and 150 beats/min, normal variability between 6 and 15 b/min, no accelerations, and no fetal movements), fetuses were randomized at a 1:1 ratio to either of the two groups. Fetuses in group A (n = 105) received acoustic stimulation after 10 min from the beginning of the CTG, whereas fetuses in group B received no stimulation (n = 105). The outcome variables investigated were the lapse of time between the beginning of the CTG and the occurrence of the first accelera-tion, and the lapse of time between the beginning of the CTG and the first fetal movement noticed. Results: The lapse of time between the beginning of the CTG and the occurrence of the first acceleration was significantly shorter in the group with acoustic stimulation compared to the other group (14.87 ± 5.01 vs. 21.90 ± 6.94 min, p-value < 0.001 log-rank test). Similarly, the lapse of time between the beginning of the CTG and the occurrence of the first fetal movement was significantly shorter in group A compared to group B (17.77 ± 7.62 vs. 23.28 ± 7.61 min, p-value < 0.001, log-rank test). Fetal cardiac acceleration and the occurrence of a fetal movement during the first 20 min of the CTG were more frequently recorded in group A compared to group B (respectively, 15% vs. 5% and 20% vs. 8%). Conclusion: This RCT showed an early fetal reaction following auditive stimulus, documentable by cardiotocography. Further research is needed to investigate a possible role of acoustic stimulation in utero for the prenatal diagnosis of congenital hypoacusis

How reliable is assessment of true vocal cord-arytenoid unit mobility in patients affected by laryngeal cancer? a multi-institutional study on 366 patients from the ARYFIX collaborative group

Purpose: In clinical practice the assessment of the "vocal cord-arytenoid unit" (VCAU) mobility is crucial in the staging, prognosis, and choice of treatment of laryngeal squamous cell carcinoma (LSCC). The aim of the present study was to measure repeatability and reliability of clinical assessment of VCAU mobility and radiologic analysis of posterior laryngeal extension. Methods: In this multi-institutional retrospective study, patients with LSCC-induced impairment of VCAU mobility who received curative treatment were included; pre-treatment endoscopy and contrast-enhanced imaging were collected and evaluated by raters. According to their evaluations, concordance, number of assigned categories, and inter- and intra-rater agreement were calculated. Results: Twenty-two otorhinolaryngologists evaluated 366 videolaryngoscopies (total evaluations: 2170) and 6 radiologists evaluated 237 imaging studies (total evaluations: 477). The concordance of clinical rating was excellent in only 22.7% of cases. Overall, inter- and intra-rater agreement was weak. Supraglottic cancers and transoral endoscopy were associated with the lowest inter-observer reliability values. Radiologic inter-rater agreement was low and did not vary with imaging technique. Intra-rater reliability of radiologic evaluation was optimal. Conclusions: The current methods to assess VCAU mobility and posterior extension of LSCC are flawed by weak inter-observer agreement and reliability. Radiologic evaluation was characterized by very high intra-rater agreement, but weak inter-observer reliability. The relevance of VCAU mobility assessment in laryngeal oncology should be re-weighted. Patients affected by LSCC requiring imaging should be referred to dedicated radiologists with experience in head and neck oncology

GJ 273: On the formation, dynamical evolution, and habitability of a planetary system hosted by an M dwarf at 3.75 parsec

Context. Planets orbiting low-mass stars such as M dwarfs are now considered a cornerstone in the search for life-harbouring planets. GJ 273 is a planetary system orbiting an M dwarf only 3.75 pc away, composed of two confirmed planets, GJ 273b and GJ 273c, and two promising candidates, GJ 273d and GJ 273e. Planet GJ 273b resides in the habitable zone. Currently, due to a lack of observed planetary transits, only the minimum masses of the planets are known: Mb sin ib=2.89 M⊕, Mc sin ic=1.18 M⊕, Md sin id=10.80 M⊕, and Me sin ie=9.30 M⊕. Despite being an interesting system, the GJ 273 planetary system is still poorly studied. Aims. We aim at precisely determine the physical parameters of the individual planets, in particular to break the mass–inclination degeneracy to accurately determine the mass of the planets. Moreover, we present thorough characterisation of planet GJ 273b in terms of its potential habitability. Methods. First, we explored the planetary formation and hydration phases of GJ 273 during the first 100 Myr. Secondly, we analysed the stability of the system by considering both the two- and four-planet configurations. We then performed a comparative analysis between GJ 273 and the Solar System, and searched for regions in GJ 273 which may harbour minor bodies in stable orbits, i.e. main asteroid belt and Kuiper belt analogues. Results. From our set of dynamical studies, we obtain that the four-planet configuration of the system allows us to break the mass– inclination degeneracy. From our modelling results, the masses of the planets are unveiled as: 2:89 ≤ Mb ≤ 3:03 M⊕, 1:18 ≤ Mc ≤ 1:24 M⊕, 10:80 ≤ Md ≤ 11:35 M⊕ and 9:30 ≤ Me ≤ 9:70 M⊕. These results point to a system likely composed of an Earth-mass planet, a super-Earth and two mini-Neptunes. From planetary formation models, we determine that GJ 273b was likely an efficient water captor while GJ 273c is probably a dry planet. We found that the system may have several stable regions where minor bodies might reside. Collectively, these results are used to comprehensively discuss the habitability of GJ 273bSpanish Ministry of Science and Education Ramón y Cajal programme ESP2017-87676-2-2 RYC-2012-09913CONICYT- FONDECYT/Chile Postdoctorado 3180405MIT’s Kavli Institut

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men