Validity of the Richmond Agitation-Sedation Scale (RASS) in critically ill children

Abstract Background The Richmond Agitation-Sedation Scale (RASS) is a single tool that is intuitive, is easy to use, and includes both agitation and sedation. The RASS has never been formally validated for pediatric populations. The objective of this study was to assess inter-rater agreement and criterion validity of the RASS in critically ill children. Methods To evaluate validity, the RASS score was compared to both a visual analog scale (VAS) scored by the patient’s nurse, and the University of Michigan Sedation Scale (UMSS), performed by a researcher. The nurse completed the VAS by drawing a single line on a 10-cm scale anchored by “unresponsive” and “combative.” The UMSS was used to validate the sedation portion of the RASS only, as it does not include grades of agitation. For inter-rater agreement, one researcher and the patient’s nurse simultaneously but independently scored the RASS. Results One hundred patient encounters were obtained from 50 unique patients, ages 2 months to 21 years. Of these, 27 assessments were on children who were mechanically ventilated and 73 were on children who were spontaneously breathing. In validity testing, the RASS was highly correlated with the nurse’s VAS (Spearman correlation coefficient 0.810, p < .0001) and with the UMSS (weighted kappa 0.902, p < .0001). Inter-rater agreement between nurse- and researcher-assessed RASS was excellent, with weighted kappa of 0.825 (p < .0001). Conclusions The RASS is a valid responsiveness tool for use in critically ill children. It allows for accurate assessment of awareness in mechanically ventilated and spontaneously breathing patients, and may improve our ability to titrate sedatives and assess for delirium in pediatrics

Safety and clinical activity of autologous RNA chimeric antigen receptor T-cell therapy in myasthenia gravis (MG-001): a prospective, multicentre, open-label, non-randomised phase 1b/2a study

Summary Background Chimeric antigen receptor (CAR) T cells are highly effective in treating haematological malignancies, but associated toxicities and the need for lymphodepletion limit their use in people with autoimmune disease. To explore the use of CAR T cells for the treatment of people with autoimmune disease, and to improve their safety, we engineered them with RNA (rCAR-T)—rather than the conventional DNA approach—to target B-cell maturation antigen (BCMA) expressed on plasma cells. To test the suitability of our approach, we used rCAR-T to treat individuals with myasthenia gravis, a prototypical autoantibody disease mediated partly by pathogenic plasma cells. Methods MG-001 was a prospective, multicentre, open-label, phase 1b/2a study of Descartes-08, an autologous anti-BCMA rCAR-T therapy, in adults (ie, aged ≥18 years) with generalised myasthenia gravis and a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 6 or higher. The study was done at eight sites (ie, academic medical centres or community neurology clinics) in the USA. Lymphodepletion chemotherapy was not used. In part 1 (phase 1b), participants with Myasthenia Gravis Foundation of America (MGFA) disease class III–IV generalised myasthenia gravis received three ascending doses of Descartes-08 to determine a maximum tolerated dose. In part 2 (phase 2a), participants with generalised myasthenia gravis with MGFA disease class II–IV received six doses at the maximum tolerated dose in an outpatient setting. The primary objective was to establish safety and tolerability of Descartes-08; secondary objectives were to assess myasthenia gravis disease severity and biomarkers in participants who received Descartes-08. This trial is registered with clinicaltrials.gov, NCT04146051. Findings We recruited 16 individuals for screening between Jan 7, 2020 and Aug 3, 2022. 14 participants were enrolled (n=3 in part 1, n=11 in part 2). Ten participants were women and four were men. Two individuals did not qualify due to low baseline MG-ADL score (n=1) or lack of generalised disease (n=1). Median follow-up in part 2 was 5 months (range 3–9 months). There was no dose-limiting toxicity, cytokine release syndrome, or neurotoxicity. Common adverse events were headache (six of 14 participants), nausea (five of 14), vomiting (three of 14), and fever (four of 14), which resolved within 24 h of infusion. Fevers were not associated with increased markers of cytokine release syndrome (IL-6, IL-2, and TNF). Mean improvements from baseline to week 12 were –6 (95% CI –9 to –3) for MG-ADL score, –7 (–11 to –3) for Quantitative Myasthenia Gravis score, –14 (–19 to –9) for Myasthenia Gravis Composite score, and –9 (–15 to –3) for Myasthenia Gravis Quality of Life 15-revised score. Interpretation In this first study of an rCAR-T therapy in individuals with an autoimmune disease, Descartes-08 appeared to be safe and was well tolerated. Descartes-08 infusions were followed by clinically meaningful decreases on myasthenia gravis severity scales at up to 9 months of follow-up. rCAR-T therapy warrants further investigation as a potential new treatment approach for individuals with myasthenia gravis and other autoimmune diseases. Funding Cartesian Therapeutics and National Institute of Neurological Disorders and Stroke of the National Institutes of Health

The Phase-2 Upgrade of the CMS Tracker

This is the final version, approved by the LHCC, of the CMS TDR devoted to the upgrade of the CMS tracker in view of the HL-LHC running

The Phase-2 Upgrade of the CMS Tracker

This is the final version, approved by the LHCC, of the CMS TDR devoted to the upgrade of the CMS tracker in view of the HL-LHC running

Search for long-lived particles decaying in the CMS muon detectors in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search for long-lived particles (LLPs) decaying in the CMS muon detectors is presented. A data sample of proton-proton collisions at $\sqrt{s}$ = 13 TeV corresponding to an integrated luminosity of 138 fb$^{-1}$ recorded at the LHC in 2016-2018, is used. The decays of LLPs are reconstructed as high multiplicity clusters of hits in the muon detectors. In the context of twin Higgs models, the search is sensitive to LLP masses from 0.4 to 55 GeV and a broad range of LLP decay modes, including decays to hadrons, $\tau$ leptons, electrons, or photons. No excess of events above the standard model background is observed. The most stringent limits to date from LHC data are set on the branching fraction of the Higgs boson decay to a pair of LLPs with masses below 10 GeV. This search also provides the best limits for various intervals of LLP proper decay length and mass. Finally, this search sets the first limits at the LHC on a dark quantum chromodynamic sector whose particles couple to the Higgs boson through gluon, Higgs boson, photon, vector, and dark-photon portals, and is sensitive to branching fractions of the Higgs boson to dark quarks as low as 2$\times$10$^{-3}$

Search for long-lived particles decaying in the CMS muon detectors in proton-proton collisions at s\sqrt{s} = 13 TeV

International audienceA search for long-lived particles (LLPs) decaying in the CMS muon detectors is presented. A data sample of proton-proton collisions at $\sqrt{s}$ = 13 TeV corresponding to an integrated luminosity of 138 fb$^{-1}$ recorded at the LHC in 2016-2018, is used. The decays of LLPs are reconstructed as high multiplicity clusters of hits in the muon detectors. In the context of twin Higgs models, the search is sensitive to LLP masses from 0.4 to 55 GeV and a broad range of LLP decay modes, including decays to hadrons, $\tau$ leptons, electrons, or photons. No excess of events above the standard model background is observed. The most stringent limits to date from LHC data are set on the branching fraction of the Higgs boson decay to a pair of LLPs with masses below 10 GeV. This search also provides the best limits for various intervals of LLP proper decay length and mass. Finally, this search sets the first limits at the LHC on a dark quantum chromodynamic sector whose particles couple to the Higgs boson through gluon, Higgs boson, photon, vector, and dark-photon portals, and is sensitive to branching fractions of the Higgs boson to dark quarks as low as 2$\times$10$^{-3}$