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1.
Pathogens ; 12(12)2023 Nov 28.
Artículo en Inglés | MEDLINE | ID: mdl-38133281

RESUMEN

Bronchiolitis is a viral respiratory infection, with respiratory syncytial virus (RSV) being the most frequent agent, requiring hospitalization in 1% of affected children. However, there continues to be a noteworthy incidence of antibiotic prescription in this setting, further exacerbating the global issue of antibiotic resistance. This study, conducted at Severo Ochoa Hospital in Madrid, Spain, focused on antibiotic usage in children under 2 years of age who were hospitalized for bronchiolitis between 2004 and 2022. In that time, 5438 children were admitted with acute respiratory infection, and 1715 infants (31.5%) with acute bronchiolitis were included. In total, 1470 (87%) had a positive viral identification (66% RSV, 32% HRV). Initially, antibiotics were prescribed to 13.4% of infants, but this percentage decreased to 7% during the COVID-19 pandemic thanks to adherence to guidelines and the implementation of rapid and precise viral diagnostic methods in the hospital. HBoV- and HAdV-infected children and those with viral coinfections were more likely to receive antibiotics in the univariate analysis. A multivariate logistic regression analysis revealed a statistically independent association between antibiotic prescription and fever > 38 °C (p < 0.001), abnormal chest-X ray (p < 0.001), ICU admission (p = 0.015), and serum CRP (p < 0.001). In conclusion, following guidelines and the availability of rapid and reliable viral diagnostic methods dramatically reduces the unnecessary use of antibiotics in infants with severe bronchiolitis.

2.
Sci Transl Med ; 11(476)2019 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-30674657

RESUMEN

Retinoblastoma is a pediatric solid tumor of the retina activated upon homozygous inactivation of the tumor suppressor RB1 VCN-01 is an oncolytic adenovirus designed to replicate selectively in tumor cells with high abundance of free E2F-1, a consequence of a dysfunctional RB1 pathway. Thus, we reasoned that VCN-01 could provide targeted therapeutic activity against even chemoresistant retinoblastoma. In vitro, VCN-01 effectively killed patient-derived retinoblastoma models. In mice, intravitreous administration of VCN-01 in retinoblastoma xenografts induced tumor necrosis, improved ocular survival compared with standard-of-care chemotherapy, and prevented micrometastatic dissemination into the brain. In juvenile immunocompetent rabbits, VCN-01 did not replicate in retinas, induced minor local side effects, and only leaked slightly and for a short time into the blood. Initial phase 1 data in patients showed the feasibility of the administration of intravitreous VCN-01 and resulted in antitumor activity in retinoblastoma vitreous seeds and evidence of viral replication markers in tumor cells. The treatment caused local vitreous inflammation but no systemic complications. Thus, oncolytic adenoviruses targeting RB1 might provide a tumor-selective and chemotherapy-independent treatment option for retinoblastoma.


Asunto(s)
Adenoviridae/fisiología , Terapia Molecular Dirigida , Virus Oncolíticos/fisiología , Proteína de Retinoblastoma/metabolismo , Retinoblastoma/metabolismo , Transducción de Señal , Animales , Línea Celular Tumoral , Citotoxicidad Inmunológica , Humanos , Ratones , Metástasis de la Neoplasia , Conejos , Retinoblastoma/inmunología , Retinoblastoma/patología , Análisis de Supervivencia , Distribución Tisular , Investigación Biomédica Traslacional , Resultado del Tratamiento , Replicación Viral , Ensayos Antitumor por Modelo de Xenoinjerto
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