Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Universal Dependencies 2.3

Universal Dependencies is a project that seeks to develop cross-linguistically consistent treebank annotation for many languages, with the goal of facilitating multilingual parser development, cross-lingual learning, and parsing research from a language typology perspective. The annotation scheme is based on (universal) Stanford dependencies (de Marneffe et al., 2006, 2008, 2014), Google universal part-of-speech tags (Petrov et al., 2012), and the Interset interlingua for morphosyntactic tagsets (Zeman, 2008)

Universal Dependencies 2.11

Universal Dependencies is a project that seeks to develop cross-linguistically consistent treebank annotation for many languages, with the goal of facilitating multilingual parser development, cross-lingual learning, and parsing research from a language typology perspective. The annotation scheme is based on (universal) Stanford dependencies (de Marneffe et al., 2006, 2008, 2014), Google universal part-of-speech tags (Petrov et al., 2012), and the Interset interlingua for morphosyntactic tagsets (Zeman, 2008)

Centrality dependence of the charged-particle multiplicity density at mid-rapidity in Pb-Pb collisions at sNN\sqrt{s_{NN}} = 2.76 TeV

The centrality dependence of the charged-particle multiplicity density at mid-rapidity in Pb-Pb collisions at $\sqrt{s_{NN}}$ = 2.76 TeV is presented. The charged-particle density normalized per participating nucleon pair increases by about a factor 2 from peripheral (70-80%) to central (0-5%) collisions. The centrality dependence is found to be similar to that observed at lower collision energies. The data are compared with models based on different mechanisms for particle production in nuclear collisions.The centrality dependence of the charged-particle multiplicity density at mid-rapidity in Pb-Pb collisions at $\sqrt{s_{\rm NN}}$ = 2.76 TeV is presented. The charged-particle density normalized per participating nucleon pair increases by about a factor 2 from peripheral (70-80%) to central (0-5%) collisions. The centrality dependence is found to be similar to that observed at lower collision energies. The data are compared with models based on different mechanisms for particle production in nuclear collisions

Production of Λ\Lambda and KS0{\rm K}^{0}_{\rm S} in jets in p-Pb collisions at sNN=5\sqrt{s_{\rm NN}} = 5 TeV and pp collisions at s=7\sqrt{s} = 7 TeV

The production of $\Lambda$ baryons and ${\rm K}^{0}_{\rm S}$ mesons (${\rm V}^{0}$ particles) was measured in p-Pb collisions at $\sqrt{s_{\rm NN}} = 5$ TeV and pp collisions at $\sqrt{s} = 7$ TeV with ALICE at the LHC. The production of these strange particles is studied separately for particles associated with hard scatterings and the underlying event to shed light on the baryon-to-meson ratio enhancement observed at intermediate transverse momentum ($p_{\rm T}$) in high multiplicity pp and p-Pb collisions. Hard scatterings are selected on an event-by-event basis with jets reconstructed with the anti-$k_{\rm T}$ algorithm using charged particles. The production of strange particles associated with jets $p_{\rm T,\;jet}^{\rm ch}>10$ GeV/$c$ is reported as a function of $p_{\rm T}$ in both systems; and its dependence on $p_{\rm T}$ with jets $p_{\rm T,\;jet}^{\rm ch}>20$ GeV/$c$ and on angular distance from the jet axis, $R({\rm V}^{0},\;{\rm jet})$, for jets with $p_{\rm T,\;jet}^{\rm ch} > 10$ GeV/$c$ are reported in p-Pb collisions. The results are compared with the strange particle production in the underlying event. The $\Lambda/{\rm K}^{0}_{\rm S}$ ratio associated with jets in p-Pb collisions for $R({\rm V}^{0},\;{\rm jet})<0.4$ is consistent with the ratio measured in pp collisions and with the expectation of jets fragmenting in vacuum given by the PYTHIA event generator

Λc+\Lambda^+_c production in pppp and in pp-Pb collisions at sNN\sqrt {s_{NN}}=5.02 TeV

International audienceThe production cross section of prompt $\mathrm{\Lambda_{c}^{+}}$ charm baryons was measured with the ALICE detector at the LHC at midrapidity in proton-proton (pp) and proton-lead (p-Pb) collisions at a centre-of-mass energy per nucleon pair of $\sqrt{s_\mathrm{NN}} = 5.02$ TeV. The $\mathrm{\Lambda_{c}^{+}}$ and $\rm {\overline{\Lambda}{}_c^-}$ baryons were reconstructed in the hadronic decay channels $\rm \Lambda_{c}^{+} \rightarrow p K^{-}\pi^{+}$ and $\rm \Lambda_{c}^{+}\to p K^{0}_{S}$ and respective charge conjugates. The measured differential cross sections as a function of transverse momentum ($p_{\rm T}$) and the $p_{\rm T}$-integrated $\mathrm{\Lambda_{c}^{+}}$ production cross section in pp and in p-Pb collisions are presented. The $\mathrm{\Lambda_{c}^{+}}$ nuclear modification factor ($R_\mathrm{pPb}$), calculated from the cross sections in pp and in p-Pb collisions, is presented and compared with the $R_\mathrm{pPb}$ of D mesons. The $\mathrm {\Lambda_{c}^{+}}/\mathrm {D^0}$ ratio is also presented and compared with the light-flavour baryon-to-meson ratios p$/\pi$ and $\Lambda /\mathrm {K^0_S}$, and measurements from other LHC experiments. The results are compared to predictions from model calculations and Monte Carlo event generators

Measurement of Prompt D0^{0}, Λc+\Lambda_{c}^{+}, and Σc0,++\Sigma_{c}^{0,++}(2455) Production in Proton–Proton Collisions at s\sqrt s = 13 TeV

International audienceThe pT-differential production cross sections of prompt D0, Λc+, and Σc0,++(2455) charmed hadrons are measured at midrapidity (|y|&lt;0.5) in pp collisions at s=13  TeV. This is the first measurement of Σc0,++ production in hadronic collisions. Assuming the same production yield for the three Σc0,+,++ isospin states, the baryon-to-meson cross section ratios Σc0,+,++/D0 and Λc+/D0 are calculated in the transverse momentum (pT) intervals 2&lt;pT&lt;12 and 1&lt;pT&lt;24  GeV/c. Values significantly larger than in e+e- collisions are observed, indicating for the first time that baryon enhancement in hadronic collisions also extends to the Σc. The feed-down contribution to Λc+ production from Σc0,+,++ is also reported and is found to be larger than in e+e- collisions. The data are compared with predictions from event generators and other phenomenological models, providing a sensitive test of the different charm-hadronization mechanisms implemented in the models

Measurements of mixed harmonic cumulants in Pb–Pb collisions at sNN\sqrt {s_{NN}} = 5.02 TeV

Correlations between moments of different flow coefficients are measured in Pb–Pb collisions at $\sqrt {s_{NN}}$ = 5.02 TeV recorded with the ALICE detector. These new measurements are based on multiparticle mixed harmonic cumulants calculated using charged particles in the pseudorapidity region |η|<0.8 with the transverse momentum range 0.2 < $p_T$ < 5.0 GeV/c . The centrality dependence of correlations between two flow coefficients as well as the correlations between three flow coefficients, both in terms of their second moments, are shown. In addition, a collection of mixed harmonic cumulants involving higher moments of $v_2$ and $v_3$ is measured for the first time, where the characteristic signature of negative, positive and negative signs of four-, six- and eight-particle cumulants are observed, respectively. The measurements are compared to the hydrodynamic calculations using iEBE-VISHNU with AMPT and TRENTo initial conditions. It is shown that the measurements carried out using the LHC Run 2 data in 2015 have the precision to explore the details of initial-state fluctuations and probe the nonlinear hydrodynamic response of $v_2$ and $v_3$ to their corresponding initial anisotropy coefficients $ε_2$ and $ε_3$ . These new studies on correlations between three flow coefficients as well as correlations between higher moments of two different flow coefficients will pave the way to tighten constraints on initial-state models and help to extract precise information on the dynamic evolution of the hot and dense matter created in heavy-ion collisions at the LHC

Inclusive J/ψ\psi production at midrapidity in pp collisions at s = 13\sqrt{s}~=~13 TeV

We report on the inclusive J/$\psi$ production cross section measured at the CERN Large Hadron Collider in proton-proton collisions at a centre-of-mass energy $\sqrt{s}~=~13$ TeV. The J/$\psi$ mesons are reconstructed in the $\rm e^{+} e^{-}$ decay channel and the measurements are performed at midrapidity ($|y|<0.9$) in the transverse-momentum interval $0< p_{\rm T} <40$ GeV/$c$, using a minimum bias data sample corresponding to an integrated luminosity $L_{\text{int}} = 32.2~\text{nb}^{-1}$ and an Electromagnetic Calorimeter triggered data sample with $L_{\text{int}} = 8.3~\mathrm{pb}^{-1}$. The $p_{\rm T}$-integrated J/$\psi$ production cross section at midrapidity, computed using the minimum bias data sample, is $\text{d}\sigma/\text{d}y|_{y=0} = 8.97\pm0.24~(\text{stat})\pm0.48~(\text{syst})\pm0.15~(\text{lumi})~\mu\text{b}$. An approximate logarithmic dependence with the collision energy is suggested by these results and available world data, in agreement with model predictions. The integrated and $p_{\rm T}$-differential measurements are compared with measurements in pp collisions at lower energies and with several recent phenomenological calculations based on the non-relativistic QCD and Color Evaporation models