This study was undertaken to investigate the role of afferent spontaneous electrical activity in regulating death of target cells in the developing mammalian visual system. We show here that naturally occurring cell death in the rat superior colliculus is greatly augmented when the spontaneous firing of retinal ganglion cells is transiently blocked with TTX. An increased number of dying cells is already observed after 1 hr of afferent blockade. A 50% increase of cell death is reached after 3 hr of blockade, an effect that closely parallels increased cell death caused by eye enucleation after similar intervals of time. These results suggest that, during development, input cells exert a trophic action on target cells, which is prevented by silencing input electrical activity. A likely explanation of this effect is that the spontaneous firing of input cells causes the release by afferent fibers of a trophic agent promoting the survival of target cells.
Objective
To summarize evidence regarding efficacy of anti-TNFα in childhood chronic uveitis, refractory to common DMARDs.
Methods
An updated systematic search was conducted between November 2012 and January 2020. Studies investigating the efficacy of anti-TNFα therapy, in children of ages <16 years, as the first biologic treatment for childhood chronic uveitis, refractory to topical and/or systemic steroid and at least one DMARD were eligible for inclusion. The primary outcome measure was the improvement of intraocular inflammation according to Standardization of Uveitis Nomenclature Working Group criteria. A combined estimate of the proportion of children responding to etanercept (ETA), infliximab (INF), and adalimumab (ADA) was determined.
Results
We identified 1677 articles of which 37 articles were eligible. Three were randomized controlled trials, one on ETA and two on ADA, and were excluded from pooled analysis. From the observational studies, a total of 487 children were identified: 226 received ADA, 213 INF and 48 ETA. The proportion of responding children was 86% (95% CI: 76%, 95%) for ADA, 68% (95% CI: 50%, 85%) for INF and 36% (95% CI: 9%, 67%) for ETA. Pooled analysis showed clear differences (χ2 = 32.2, P < 0.0001): ADA and INF were both significantly superior to ETA (χ2 = 26.8, P < 0.0001, and χ2 = 7.41, P < 0.006, respectively), ADA significantly superior to INF (χ2 = 13.4, P < 0.0002).
Conclusion
This meta-analysis, consistent with recent randomized controlled trial data, suggests the efficacy of ADA and INF in childhood chronic uveitis treatment. However, ADA results were superior to those of INF in this clinical setting.
The fast diffusion of the SARS-CoV-2 pandemic have called for an equally rapid evolution of the therapeutic options.The Human recombinant monoclonal antibodies (mAbs) have recently been approved by the Food and Drug Administration (FDA) and by the Italian Medicines Agency (AIFA) in subjects aged ≥12 with SARS-CoV-2 infection and specific risk factors.Currently the indications are specific for the use of two different mAbs combination: Bamlanivimab+Etesevimab (produced by Eli Lilly) and Casirivimab+Imdevimab (produced by Regeneron).These drugs have shown favorable effects in adult patients in the initial phase of infection, whereas to date few data are available on their use in children.AIFA criteria derived from the existing literature which reports an increased risk of severe COVID-19 in children with comorbidities. However, the studies analyzing the determinants for progression to severe disease are mainly monocentric, with limited numbers and reporting mostly generic risk categories.Thus, the Italian Society of Pediatrics invited its affiliated Scientific Societies to produce a Consensus document based on the revision of the criteria proposed by AIFA in light of the most recent literature and experts’ agreement.This Consensus tries to detail which patients actually have the risk to develop severe disease, analyzing the most common comorbidities in children, in order to detail the indications for mAbs administration and to guide the clinicians in identifying eligible patients.
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