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.
Antimicrobial lock solutions (ALT) in combination with systemic antibiotics can represent a valid option to attempt central venous catheter (CVC) salvage in the case of catheter-related and central-line-associated bloodstream infections (CRBSI and CLABSI). However, data concerning the effectiveness and safety of ALT in children are limited. We aimed to share our center’s experience in order to contribute to investigations into the causes of ALT failure in the pediatric population. All children consecutively admitted to Meyer Children’s Hospital, University of Florence, Italy, from 1 April 2016 to 30 April 2022, who received salvage ALT to treat an episode of CRBSI/CLABSI, were reviewed. According to ALT failure or success, children were compared with the aim of identifying the risk factors for unsuccessful ALT outcome. Data from 28 children, 37 CLABSI/CRBSI episodes, were included. ALT was associated with clinical and microbiologic success in 67.6% (25/37) of children. No statistically significant differences were observed between the two groups, successes and failures, considering age, gender, reason for use, duration, insertion, type and presence of insertion site infection of the CVC, laboratory data and number of CRBSI episodes. Nevertheless, a trend towards a higher success rate was observed for a dwell time of 24 h for the entire duration of ALT (88%; 22/25 vs. 66.7%; 8/12; p = 0.1827), while the use of taurolidine and the infections sustained by MDR bacteria were associated with a tendency toward greater failure (25%; 3/12 vs. 4%; 1/25; p = 0.1394; 60%; 6/10 vs. 33.3%; 8/24; p = 0.2522). No adverse events, except one CVC occlusion, were observed. ALT combined with systemic antibiotics appears to be an effective and safe strategy for treating children with CLABSI/CRBSI episodes.
Immunoglobulin A vasculitis (IgAV) is the most common childhood vasculitis affecting small vessels. No clear recommendations are available for severe pediatric cases, and until now, anti‐TNF agents have had a limited role in IgAV management. In this report, we describe a pediatric case of severe IgAV, successfully treated with combined therapy including the anti‐TNF, infliximab.
BackgroundHenoch-Schönlein purpura (HSP) is a systemic small vessel vasculitis and represent the most common cause of non-thrombocytopenic purpura in children; vasculitis very rarely can involve internal organs. Central nervous system (CNS) is exceptional.ObjectivesWe report the case of a patient with CNS vasculitis who presented HSP 4 months after the stroke and during corticosteroid withdrawal.MethodsCase reportResultsA 9-year-old Caucasian boy was admitted to our hospital due to sudden onset of severe headache and left faciobrachial hemiparesis associated with facial palsy and dysarthria. Brain MRI revealed hyperintense signal changes in amygdala, putamen, and internal capsule, suggestive of recent cerebral ischemic lesion. Magnetic resonance angiography showed asymmetry of internal carotid arteries and middle cerebral artery stenosis, suggestive for a vasculitic-inflammatory nature. He received high dose intravenous methylprednisolone, followed by oral corticosteroids with nearly complete recovery. He was discharged on oral prednisone and low-dose aspirin. In the following months a slow tapering of prednisone was attempted. Four months after the stroke, while receiving prednisolone 0.5 mg/kg/day, he presented with sudden onset of purpuric rash on extensor surfaces of the lower extremities, buttocks and arthralgia of the upper and lower extremities. Painful scrotal swelling and abdominal pain were also present. Serial urinalyses were normal. The patient underwent a second MRI of the brain, which ruled out new-onset inflammatory lesions. Therefore, he received intravenous high dose steroids, with complete remission. Sequencing of adenosine deaminase 2 (ADA2) gene ruled out ADA2 deficiency.ConclusionWe report a case of CNS vasculitis preceding HSP by several months; intriguingly, HSP developed while the patient was under corticosteroid treatment. The exact nature of the association needs to be clarified, to determine if the association was determined by a common pathogenic mechanism or by chance.References[1] AkÇaboy M, Fidan K, Kandur Y, et al. Cerebral Vasculitis in Henoch-Schönlein Purpura: A Case Report. Arch Rheumatol. 2017. Mar 24;32(3):264-267.[2] Bérubé MD, Blais N, Lanthier S. Neurologic manifestations of Henoch-Schönlein purpura. Handb Clin Neurol. 2014;120:1101-11.[3] Suh JS, Hahn WH, Cho BS, Kim SD, Hong IK. A rare case of cerebral vasculitis in Henoch-Schönlein purpura with emphasis on the diagnostic value of magnetic resonance angiography (MRA) and single-photon emission computed tomography (SPECT) given normal magnetic resonance imaging (MRI). Int J Dermatol. 2010 Jul;49(7):803-5.AcknowledgementFederica Barbati, MD; Sara Abu-Rumeileh, MDDisclosure of Interestsedoardo marrani: None declared, Gabriele Simonini Grant/research support from: Abbvie, Speakers bureau: Abbvie, Eleonora Fusco: None declared, Ilaria Maccora: None declared, Anna Rosati: None declared, Rolando Cimaz: None declared, Teresa Giani: None declared
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