; for the CORIMUNO-19 Collaborative Group IMPORTANCE Severe pneumonia with hyperinflammation and elevated interleukin-6 is a common presentation of coronavirus disease 2019 (COVID-19). OBJECTIVE To determine whether tocilizumab (TCZ) improves outcomes of patients hospitalized with moderate-to-severe COVID-19 pneumonia. DESIGN, SETTING, AND PARTICPANTS This cohort-embedded, investigator-initiated, multicenter, open-label, bayesian randomized clinical trial investigating patients with COVID-19 and moderate or severe pneumonia requiring at least 3 L/min of oxygen but without ventilation or admission to the intensive care unit was conducted between March 31, 2020, to April 18, 2020, with follow-up through 28 days. Patients were recruited from 9 university hospitals in France. Analyses were performed on an intention-to-treat basis with no correction for multiplicity for secondary outcomes. INTERVENTIONS Patients were randomly assigned to receive TCZ, 8 mg/kg, intravenously plus usual care on day 1 and on day 3 if clinically indicated (TCZ group) or to receive usual care alone (UC group). Usual care included antibiotic agents, antiviral agents, corticosteroids, vasopressor support, and anticoagulants. MAIN OUTCOMES AND MEASURES Primary outcomes were scores higher than 5 on the World Health Organization 10-point Clinical Progression Scale (WHO-CPS) on day 4 and survival without need of ventilation (including noninvasive ventilation) at day 14. Secondary outcomes were clinical status assessed with the WHO-CPS scores at day 7 and day 14, overall survival, time to discharge, time to oxygen supply independency, biological factors such as C-reactive protein level, and adverse events. RESULTS Of 131 patients, 64 patients were randomly assigned to the TCZ group and 67 to UC group; 1 patient in the TCZ group withdrew consent and was not included in the analysis. Of the 130 patients, 42 were women (32%), and median (interquartile range) age was 64 (57.1-74.3) years. In the TCZ group, 12 patients had a WHO-CPS score greater than 5 at day 4 vs 19 in the UC group (median posterior absolute risk difference [ARD] −9.0%; 90% credible interval [CrI], −21.0 to 3.1), with a posterior probability of negative ARD of 89.0% not achieving the 95% predefined efficacy threshold. At day 14, 12% (95% CI −28% to 4%) fewer patients needed noninvasive ventilation (NIV) or mechanical ventilation (MV) or died in the TCZ group than in the UC group (24% vs 36%, median posterior hazard ratio [HR] 0.58; 90% CrI, 0.33-1.00), with a posterior probability of HR less than 1 of 95.0%, achieving the predefined efficacy threshold. The HR for MV or death was 0.58 (90% CrI, 0.30 to 1.09). At day 28, 7 patients had died in the TCZ group and 8 in the UC group (adjusted HR, 0.92; 95% CI 0.33-2.53). Serious adverse events occurred in 20 (32%) patients in the TCZ group and 29 (43%) in the UC group (P = .21). CONCLUSIONS AND RELEVANCE In this randomized clinical trial of patients with COVID-19 and pneumonia requiring oxygen support but not admitted to the intensive care...

Background Patients with COVID-19 pneumonia have an excess of inflammation and increased concentrations of cytokines including interleukin-1 (IL-1). We aimed to determine whether anakinra, a recombinant human IL-1 receptor antagonist, could improve outcomes in patients in hospital with mild-to-moderate COVID-19 pneumonia.Methods In this multicentre, open-label, Bayesian randomised clinical trial (CORIMUNO-ANA-1), nested within the CORIMUNO-19 cohort, we recruited patients from 16 University hospitals in France with mild-to-moderate COVID-19 pneumonia, severe acute respiratory syndrome coronavirus 2 infection confirmed by real-time RT-PCR, requiring at least 3 L/min of oxygen by mask or nasal cannula but without ventilation assistance, a score of 5 on the WHO Clinical Progression Scale (WHO-CPS), and a C-reactive protein serum concentration of more than 25 mg/L not requiring admission to the intensive care unit at admission to hospital. Eligible patients were randomly assigned (1:1) using a web-based secure centralised system, stratified by centre and blocked with varying block sizes (randomly of size two or four), to either usual care plus anakinra (200 mg twice a day on days 1-3, 100 mg twice on day 4, 100 mg once on day 5) or usual care alone. Usual care was provided at the discretion of the site clinicians. The two coprimary outcomes were the proportion of patients who had died or needed non-invasive or mechanical ventilation by day 4 (ie, a score of >5 on the WHO-CPS) and survival without need for mechanical or non-invasive ventilation (including high-flow oxygen) at day 14. All analyses were done on an intention-to-treat basis. The trial is registered with ClinicalTrials.gov, NCT04341584, and is now closed to accrual. FindingsBetween April 8 and April 26, 2020, we screened 153 patients. The study was stopped early following the recommendation of the data and safety monitoring board, after the recruitment of 116 patients: 59 were assigned to the anakinra group, and 57 were assigned to the usual care group. Two patients in the usual care group withdrew consent and were not analysed. In the analysable population, the median age was 66 years (IQR 59 to 76) and 80 (70%) participants were men. In the anakinra group, 21 (36%) of 59 patients had a WHO-CPS score of more than 5 at day 4 versus 21 (38%) of 55 in the usual care group (median posterior absolute risk difference [ARD] -2•5%, 90% credible interval [CrI] -17•1 to 12•0), with a posterior probability of ARD of less than 0 (ie, anakinra better than usual care) of 61•2%. At day 14, 28 (47%; 95% CI 33 to 59) patients in the anakinra group and 28 (51%; 95% CI 36 to 62) in the usual care group needed ventilation or died, with a posterior probability of any efficacy of anakinra (hazard ratio [HR] being less than 1) of 54•5% (median posterior HR 0•97; 90% CrI 0•62 to 1•52). At day 90, 16 (27%) patients in the anakinra group and 15 (27%) in the usual care group had died. Serious adverse events occurred in 27 (46%) patients in the anakinra group and 21 (38%) in the usu...

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This study aimed at testing human skin wound healing improvement by a 21-day supplementation of 1.0 g ascorbic acid (AA) and 0.2 g pantothenic acid (PA). 49 patients undergoing surgery for tattoos, by the successive resections procedure, entered a double-blind, prospective and randomized study. Tests performed on both skin and scars determined: hydroxyproline concentrations, number of fibroblasts, trace element contents and mechanical properties. In the 18 supplemented patients, it was shown that in skin (day 8) Fe increased (p < 0.05) and Mn decreased (p < 0.05); in scars (day 21), Cu (p = 0.07) and Mn (p < 0.01) decreased, and Mg (p < 0.05) increased; the mechanical properties of scars in group A were significantly correlated to their contents in Fe, Cu and Zn, whereas no correlation was shown in group B. In blood, AA increased after surgery with supplementation, whereas it decreased in controls. Although no major improvement of the wound healing process could be documented in this study, our results suggest that the benefit of AA and PA supplementation could be due to the variations of the trace elements, as they are correlated to mechanical properties of the scars.

The aim of this prospective study was to evaluate the usefulness of fetal weight estimation in a prospective study, based on formulae derived from a previous retrospective study, using forward stepwise multiple regression analysis. Three-dimensional ultrasound was used to make reproducible measurement of limb circumferences, which formed the basis of our models. A total of 213 women with singleton pregnancies were scanned in the week prior to delivery and the following variables were measured: biparietal diameter, head circumference, transverse abdominal diameter, abdominal circumference, femur length, thigh circumference and arm circumference. The whole population was divided into three subgroups according to the abdominal circumference (< 10th centile, 10-90th centile, and > 90th centile). We demonstrated the need for only two models for accurate fetal weight estimation, one for the small-for-dates fetuses and a second for the others. The most accurate results were obtained for the macrosomic fetuses with a standard deviation of 8.8%. Our data confirm the usefulness of measurement of fetal thigh circumference for the the small-for-dates-fetuses and arm circumference for the other groups. We concluded that the use of three-dimensional ultrasound could facilitate the accurate prediction of fetal weight.

The improvement of the wound healing process in humans by vitamin supplements is still controversial because of the lack of a clearly demonstrated correlation with the mechanical properties of scars. Objective: The aim of this work was to study the effects of high doses of ascorbic acid (AA) and pantothenic acid (PA) on the wound healing process of human skin. Method: Two groups of patients undergoing surgery for tattoo removal by the successive resection procedure received AA (1 or 3 g/day) and PA (0.2 or 0.9 g/day). More than 80 mechanical, biological and histological parameters were investigated in both preoperated skin and the scars. Results: The breaking energy of scars was higher in group 2, and energy and treatment were directly correlated (p = 0.006). Mg and Mn significantly rose in group 2 whereas Fe decreased in a dose-dependent manner. Intragroup comparison showed patient and treatment effects for Mg, a time •treatment effect for Cu and a treatment effect for Fe. Conclusion: The degree and rapidity of variations rather than the variations of the absolute values themselves of fibroblasts, hydroxyproline, Fe, Cu and Mg are significantly related to the enhancement of the mechanical properties of scars. From this study, it may be assumed that in order to obtain ‘better’, more solid and resistant scars, the decrease of Fe must be quick and acute in order to avoid the harmful effects of toxic radicals; the increase of Cu, Mg and Mn must be early and high in order to have more stable and solid collagen.

A large number of formulae have been published for fetal weight estimation. This study examines the possibility of using three-dimensional ultrasound to measure the limb circumference. This technology provides us with the opportunity to visualize two simultaneous, orthogonal planes, allowing the exact determination of the transverse plane at the mid-point of the limb. A total of 157 patients were scanned in the week prior to delivery. The following variables were measured in 154 fetuses: biparietal diameter, head circumference, transverse abdominal diameter, abdominal circumference, femur length, thigh circumference and arm circumference. The whole population was split into three subgroups according to the abdominal circumference centile (< 10th centile, 10-90th centile, and > 90th centile), because this single variable has the strongest correlation with neonatal weight (R = 0.901). With forward stepwise multiple regression analysis, four models were elaborated, one for the whole population and one for each subgroup. The small-for-dates fetuses need a targeted formula including only two variables, thigh circumference and femur length. Our data suggest that the thigh circumference measurement improves the estimation for growth-retarded fetuses and that the arm circumference improves the weight prediction for the others. The measurement of the two variables, made possible with three-dimensional ultrasound, has improved our results in fetal weight estimation.