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

Chemical composition, respiration and feeding rates of the new alien ctenophore, Beroe ovata, in the Black Sea

Maximum daily rations of the ctenophore Beroe ovata Brugiere and predatory impacts on the Mnemiopsis leidyi A. Agassiz population were estimated via digestion time, prey biomass and predator and prey density in Sevastopol Bay and adjacent water regions. Digestion times ranged from 0.5 to 5.2 h and depended on the prey/predator weight ratio. Overall, the mean daily ration was 45% of B. ovata wet weight. Preliminary conclusions are given on the B. ovata population as an effective control of the M. leidyi population and on the dynamics and structure of the planktonic community as a whole

The ecological and physiological state of the ctenophore Mnemiopsis leidyi (Agassiz) in the Black Sea in autumn 1996

The survey was made in off-shore waters of the Black Sea near the Anatolian coast of Turkey during a research cruise of the R/V Bilim (24 Sept - 4 Oct 1996). The biomass of gelatinous macroplankton and the glycogen content in the body of the ctenophore Mnemiopsis leidyi were studied at 14 stations. Though the ctenophore still dominated the plankton in terms of biomass (average biomass +/- standard deviation 276 +/- 115 g/m(2)), this estimate was significantly lower than corresponding estimates obtained for the same months in recent years. A simultaneous reduction in the stock of small-sized fodder zooplankton and the large copepod Calanus euxinus indicates this case may be due to a general aggravation of trophic conditions for ctenophores. Data on the ctenophore's body glycogen content varied from 21 to 44 mu g/g fresh weight and accounted for 52.5 +/- 14.2% of total polysaccharide content on average, the condition of M. leidyi observed during the conducted survey corresponded to that expected after a two-day fasting period. Tentative experiments have shown that metabolic rates of the examined ctenophores were notably reduced. The rate of oxygen consumption (R, mu l O-2 . ind(-1) . h(-1)) was 1.7-1.8 less than that which would indicate a sufficient food supply; depending on the estimate of fresh body weight (UT, g) at 12-14 degrees C, it may be described by the following equation: R = 2.50 W-0.83

Population dynamics, ingestion, growth and reproduction rates of the invader Beroe ovata and its impact on plankton community in Sevastopol Bay, the Black Sea

The impact of the introduced ctenophore Beroe ovata on its prey Mnemiopsis leidyi, another invader ctenophore voraciously feeding on mesozooplankton, and consequently on the mesozooplankton community, was evaluated by undertaking both laboratory and field studies in the northern Black Sea. Ingestion and growth rates as well as the gross growth efficiency of B. ovata were estimated from laboratory experiments. The daily ration of ctenophores was related to food abundance within a wide range of prey concentration and never reached saturation. Beroe ovata required high food rations (not less than 20% of body weight per day) for growth. The abundances, biomasses and population structures of these two introduced ctenophore species were also monitored, along with mesozooplankton, in inshore waters of the northern Black Sea (i.e. Sevastopol Bay and adjacent regions) over a period of 3 years (1999-2001) which is after B. ovata's arrival. The annual dynamics of the M. leidyi population were similar for the last 3 years: very low abundances and biomass values were observed during most of the year (unlike the previous years), with a sudden increase in summer-early autumn, but only for about a 2 month period. The B. ovata bloom during the peak M. leidyi biomass resulted in the M. leidyi biomass falling sharply to extremely low values. The predatory impact of M. leidyi on prey zooplanton was found to be reduced during the period of study compared with before

Nutritional condition of female Calanus euxinus from cyclonic and anticyclonic regions of the Black Sea

The content and composition of lipids in Calanus euxinus females were studied in cyclonic and anticyclonic regions in the southern Black Sea during the period of persistent density stratification (September 1996). The lipid content of C, euxinus from cyclonic regions was greater than of individuals from anticyclonic regions (average 101.9 and 58.8 mu g ind.(-1), respectively). Total Lipid content (mainly wax esters, 70 to 72%, and triacylglycerols, 8 to 13%) of female C. euxinus was correlated with chlorophyll a (chl a) (mean integrated concentration) (r = 0.92, p < 0.005). The high correlation with chi a was shown also for wax ester content. used as a long-term index of food supply (r = 0.89, p < 0.05). The correlation between triacylglycerol content (a short-term index) and chi a was not significant (r = 0.66, p < 0.2). In cyclonic regions the mean integrated chi a concentration (0.38 mg m(-3)) (as an indicator of phytoplankton food biomass) was 1.7-fold higher than in anticyclonic areas. The same trend occurred for mean integrated concentrations of nitrate and phosphate (0.996 and 0.299 mu M in cyclonic and 0.438 and 0.061 mu M in anticyclonic regions. respectively) in the chi a containing layer. Thus, conditions for total primary productivity in cyclonic regions were more favorable than in anticyclonic ones. This was consistent with lipid levels in female C, euxinus