End of April 2020, French clinicians observed an increase in cases presenting with paediatric inflammatory multisystem syndrome (PIMS). Nationwide surveillance was set up and demonstrated temporospatial association with the coronavirus disease (COVID-19) epidemic for 156 reported cases as at 17 May: 108 were classified as confirmed (n = 79), probable (n = 16) or possible (n = 13) post-COVID-19 PIMS cases. A continuum of clinical features from Kawasaki-like disease to myocarditis was observed, requiring intensive care in 67% of cases.

Transcranial Doppler (TCD) is used to detect children with sickle cell anemia (SCA) who are at risk for stroke, and transfusion programs significantly reduce stroke risk in patients with abnormal TCD. We describe the predictive factors and outcomes of cerebral vasculopathy in the Cré teil newborn SCA cohort (n ‫؍‬ 217 SS/ S␤ 0 ), who were early and yearly screened with TCD since 1992. Magnetic resonance imaging/magnetic resonance angiography was performed every 2 years after age 5 (or earlier in case of abnormal TCD). A transfusion program was recommended to patients with abnormal TCD and/or stenoses, hydroxyurea to symptomatic patients in absence of macrovasculopathy, and stem cell transplantation to those with human leukocyte antigengenoidentical donor. Mean follow-up was 7.7 years (1609 patient-years). The cumulative risks by age 18 years were 1.9% (95% confidence interval [95% CI] 0.6%-5.9%) for overt stroke, 29.6% (95% CI 22.8%-38%) for abnormal TCD, which reached a plateau at age 9, whereas they were 22.6% (95% CI 15.0%-33.2%) for stenosis and 37.1% (95% CI 26.3%-50.7%) for silent stroke by age 14. Cumulating all events (stroke, abnormal TCD, stenoses, silent strokes), the cerebral risk by age 14 was 49.9% (95% CI 40.5%-59.3%); the independent predictive factors for cerebral risk were baseline reticulocytes count (hazard ratio 1.003/L ؋ 10 9 /L increase, 95% CI 1.000-1.006; P ‫؍‬ .04) and lactate dehydrogenase level (hazard ratio 2.78/1 IU/mL increase, 95% CI1.33-5.81; P ‫؍‬ .007). Thus, early TCD screening and intensification therapy allowed the reduction of stroke-risk by age 18 from the previously reported 11% to 1.9%. In contrast, the 50% cumulative cerebral risk suggests the need for more preventive intervention. (Blood. 2011;117(4):1130-1140)

Polymorphonuclear neutrophil (PMN) migration across basement membrane is thought to be dependent on the degradation of membrane constituents. PMN gelatinase B, a metalloproteinase able to degrade type IV collagen, may be involved in this phenomenon. PMN gelatinase B is released in the extracellular medium as a latent proform and then activated, mainly by PMN elastase. We investigated the role of gelatinase B in PMN migration across a Matrigel basement membrane matrix coated onto a filter, in a Boyden chamber. The effects of gelatinase and elastase inhibitors on PMN migration in this system were tested. Chemokinesis of PMN was tested in the same Boyden chamber across a filter free of basement membrane. The agarose method was used to test the same inhibitors for effects on PMN chemotaxis. In both systems, FMLP 10(-7)M was used as a chemoattractant. Addition of 10(-8)M TIMP-1 (the preferential gelatinase B inhibitor) inhibited trans-basement membrane PMN migration by 52 +/- 6% (P<0.05), without affecting PMN chemokinesis, chemotaxis, or degranulation. Also, (Ala)(2) Pro Val chloromethyl ketone (AAPVCK) 100 micron, a specific elastase inhibitor, inhibited trans-basement membrane PMN migration by 51 +/- 8% (P<0.05), without affecting PMN chemokinesis, chemotaxis, or degranulation. The AAPVCK-TIMP combination led to a decrease in migration across Matrigel basement membrane (46 +/- 2%, P,0.05)similar to that seen with TIMP alone. AAPVCK was responsible for inhibition of gelatinase B activation, leading to a decrease in activated gelatinase from 14% to 2% of total gelatinase release (P<0.05). All these results strongly suggest that gelatinase B is a major factor of PMN migration across basement membrane and that elastase may contribute to this process by activating pro-gelatinase B.

Studies based on skin and challenge tests have shown that 12-60% of children with suspected betalactam hypersensitivity were allergic to betalactams. Responses in skin and challenge tests were studied in 1865 children with suspected betalactam allergy (i) to confirm or rule out the suspected diagnosis; (ii) to evaluate diagnostic value of immediate and non-immediate responses in skin and challenge tests; (iii) to determine frequency of betalactam allergy in those children, and (iv) to determine potential risk factors for betalactam allergy. The work-up was completed in 1431 children, of whom 227 (15.9%) were diagnosed allergic to betalactams. Betalactam hypersensitivity was diagnosed in 50 of the 162 (30.9%) children reporting immediate reactions and in 177 of the 1087 (16.7%) children reporting non-immediate reactions (p<0.001). The likelihood of betalactam hypersensitivity was also significantly higher in children reporting anaphylaxis, serum sickness-like reactions, and (potentially) severe skin reactions such as acute generalized exanthematic pustulosis, Stevens-Johnson syndrome, and drug reaction with systemic symptoms than in other children (p<0.001). Skin tests diagnosed 86% of immediate and 31.6% of non-immediate sensitizations. Cross-reactivity and/or cosensitization among betalactams was diagnosed in 76% and 14.7% of the children with immediate and non-immediate hypersensitivity, respectively. The number of children diagnosed allergic to betalactams decreased with time between the reaction and the work-up, probably because the majority of children with severe and worrying reactions were referred for allergological work-up more promptly than the other children. Sex, age, and atopy were not risk factors for betalactam hypersensitivity. In conclusion, we confirm in numerous children that (i) only a few children with suspected betalactam hypersensitivity are allergic to betalactams; (ii) the likelihood of betalactam allergy increases with earliness and/or severity of the reactions; (iii) although non-immediate-reading skin tests (intradermal and patch tests) may diagnose non-immediate sensitizations in children with non-immediate reactions to betalactams (maculopapular rashes and potentially severe skin reactions especially), the diagnostic value of non-immediate-reading skin tests is far lower than the diagnostic value of immediate-reading skin tests, most non-immediate sensitizations to betalactams being diagnosed by means of challenge tests; (iv) cross-reactivity and/or cosensitizations among betalactams are much more frequent in children reporting immediate and/or anaphylactic reactions than in the other children; (v) age, sex and personal atopy are not significant risk factors for betalactam hypersensitivity; and (vi) the number of children with diagnosed allergy to betalactams (of the immediate-type hypersensitivity especially) decreases with time between the reaction and allergological work-up. Finally, based on our experience, we also propose a practical diagnostic approach in children with suspecte...