Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Sekundärionen Massenspektrometrie in der Zentralabteilung für Chemische Analysen

Nach Beschreibungen des physikalischen Prinzips, der analytischenLeistungsdaten und der in der Zentralabteilung betriebenenSIMS-Geräte, wird eine Zusammenstellung durchgeführterEntwicklungsarbeiten und bearbeiteter Analysenanforderungengegeben. Ausgewählte Analysenaufgaben werdenhinsichtlich Zielsetzung und Ergebnis näher beschrieben.Dabei wird besonders auf die Leistungssteigerung durch dieInbetriebnahme des neuen SIMS-Gerätes IMS 4F eingegangen

Entwicklungsstand der leitprobenfreien Elementanalyse in der Funken-Massenspektrometrie mit Niedervolt-Vakuumbogenentladung und automatischer Fotoplattenauswertung

With an automatic photoplate-evaluation system in Spark-Source Mass Spectrometry, complete photoplate information is used for the concentration-procedure, that means, all isotopes of single and multiple-chargedions contribute to the analytical result. Experiments show that the ion-intensities of elements in their ionization states lie on parabolas. The parabola-position of impurity-elements within a matrix is mainly influenced by that matrix and shows a characteristic relation to the analytical result. Systematic investigations lead to a significant parameter, the so-called "mean charge number" Zi, which forms a common link between the very different parabola-positions of all elements within a matrix. This knowledge is the basis for a new evaluation procedure which, without using a calibration standard,leads to an essential improvement of the analytical result. Experiments in practical analysis work show that this method, used on many different matrices, show a maximum deviation from the certificate value by a factor of 2 (in many cases < 1.5). Analyzing the main components in alloys yields accuracies between 10 and 20%. For the standard-deviation of analysis results an upper limit of 10% was reached. The knowledge of the common Zi makes it possible, that also elements with a small amount of detected states of charge may be integrated within the normal determination of concentration. The appendix shows the detailed description of computer programs already applied for practical analysis work

Untersuchungen zur Sekundärionenbildung an sauerstoffbedeckten Oberflächen binärer metallischer Legierungen

Oxygen covered surfaces of the single phase alloys from the systems Cu-Ni and Cr-Ni were bombarded with o$_{2}^{+}$ ions. Sputtering yields were determined as a function of concentration by weight-loss measurements as were the intensities of all positivly charged secondary ions by mass spectrometry. The atomic ion emission was found to be representative for the total ion emission of an element. It means that the presence of cluster ions influences the intensities of atomic ions only insignificantly. For the atomic ions ionisation coefficients calculated from intensities, sputtering yields and concentrations are linearly dependent on the concentration for Ni-rich Cr-Ni-alloys. Cu-Ni-alloys show a nonlinear dependence. Possible reasons for these observations are discussed

Verbesserung der leitprobenfreien Analyse in der Funken-Massenspektrometrie durch vollständige Nutzung der Fotoplatteninformation

With an autanatic photoplate-evaluation systan in Spark-Source Mass Spectrometry, complete photoplate information is used for the concentration-procedure, that means, all isotopes of single and multiple-charged ions contribute to the analytical result. Experiments show that the ion-intensities of elements in their ionisation states lie on parabolas. The parabola-position of trace-elements within a matrix is mainly influenced by that matrix a.rrl shows a characteristic relation to theanalytical result. Systematic investigations lead to a significant parameter, the so-called "mean charge number" Zi, which forms a common link between the verydifferent parabola-positions of all elements within a matrix. This knowledge is the basis for a new evaluation procedure which, without using a calibration standard, leads to an essential improvement of the analytical result. Experiments with this method used on 5 different matrices show a maximum deviation fran the certificate value by a factor of 2. This result could be achieved with a low voltage discharge ion source