Concordancia interobservador del electroencefalograma integrado por amplitud en el neonato con asfixia perinatal

Introduction: Amplitude integrated electroencephalography (aEEG) is a widely tool used for neuromonitoring in the critical neonate. In the patient with perinatal asphyxia, its interpretation is key to identifying candidates for therapeutic hypothermia, detecting subclinical seizures and providing pronostic information. Our aim was to analyze the concordance in the interpretation of aEEG among neonatologists with different level of experience. Material and methods: Unicenter retrospective study of newborns ≥35 weeks with perinatal asphyxia included consecutively over a two-year period and monitored with aEEG for at least 6 h. The bedside neonatologist interpreted aEEG regarding background pattern, sleep-wake cycling, and seizures. The aEEG tracings were blindly reviewed by two neonatologists with different experience. The aEEG tracings were divided into periods of 0–3 h and 3-6 h of life, and the concordance (Cohen Kappa coefficient, k), between the two examiners and that of their consensus with the bedside neonatologist, was analyzed. Results: Seventy-five newborns were included, 5 of them were not aEEG-monitored. 132 tracings were analyzed with a very good concordance between the two examiners in the three characteristics of the aEEG. The k for the bedside neonatologist was very good for background pattern (k = 0.93), moderate (k = 0.52) for sleep-wake cycling, and weak (k = 0.32) for seizures. Conclusions: This study supports that background pattern is easily interpreted compared to sleep-wake cycling or crisis, improving when targeted training on aEEG is receivedLa electroencefalografía integrada por amplitud (aEEG) es una herramienta utilizada en la neuromonitorización del neonato crítico. En el paciente con asfixia perinatal, su interpretación es clave para identificar a los candidatos a hipotermia terapéutica, detectar crisis subclínicas y aportar información pronóstica. Nuestro objetivo fue analizar la concordancia en la interpretación del aEEG entre neonatólogos con distinto nivel de experiencia. Material y métodos: Estudio retrospectivo unicéntrico de los recién nacidos ≥ 35 semanas con asfixia perinatal incluidos consecutivamente durante un periodo de dos años y monitorizados con aEEG durante al menos 6 horas. El médico de guardia interpretó el aEEG respecto al trazado de base, los ciclos vigilia-sueño y las crisis. Los aEEG fueron revisados de forma ciega por dos neonatólogas con distinta experiencia. Se analizó la concordancia (coeficiente Kappa de Cohen, k) de los aEEG divididos en periodos de 0-3 horas y 3-6 horas de vida, entre ambas y la de su consenso con el médico de guardia. Resultados: Se incluyeron 75 neonatos, 5 de ellos no se monitorizaron. Se analizaron 132 tra- zados con una concordancia muy buena entre las dos examinadoras en las tres características del aEEG. El k respecto al médico de guardia fue muy bueno para el trazado de base (k= 0,93), moderado (k= 0,52) para los ciclos vigilia-sueño y débil (k= 0,32) para las crisis. Conclusiones: Este estudio apoya una mayor facilidad para interpretar adecuadamente el trazado de base frente a los ciclos vigilia-sueño o las crisis, mejorando cuando se recibe una formación dirigida en el aEEGEste estudio ha sido parcialmente financiado por la Gerencia Regional de Salud de Castilla y León (N.◦ de expediente GRS 827/A/13

Enhanced anti-inflammatory effects of mesenchymal stromal cells mediated by the transient ectopic expression of CXCR4 and IL10

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliationsBackground Mesenchymal stromal cells (MSCs) constitute one of the cell types most frequently used in cell therapy. Although several studies have shown the efficacy of these cells to modulate inflammation in different animal models, the results obtained in human clinical trials have been more modest. Here, we aimed at improving the therapeutic properties of MSCs by inducing a transient expression of two molecules that could enhance two different properties of these cells. With the purpose of improving MSC migration towards inflamed sites, we induced a transient expression of the C-X-C chemokine receptor type 4 (CXCR4). Additionally, to augment the anti-inflammatory properties of MSCs, a transient expression of the anti-inflammatory cytokine, interleukin 10 (IL10), was also induced. Methods Human adipose tissue-derived MSCs were transfected with messenger RNAs carrying the codon-optimized versions of CXCR4 and/or IL10. mRNA-transfected MSCs were then studied, first to evaluate whether the characteristic phenotype of MSCs was modified. Additionally, in vitro and also in vivo studies in an LPS-induced inflamed pad model were conducted to evaluate the impact associated to the transient expression of CXCR4 and/or IL10 in MSCs. Results Transfection of MSCs with CXCR4 and/or IL10 mRNAs induced a transient expression of these molecules without modifying the characteristic phenotype of MSCs. In vitro studies then revealed that the ectopic expression of CXCR4 significantly enhanced the migration of MSCs towards SDF-1, while an increased immunosuppression was associated with the ectopic expression of IL10. Finally, in vivo experiments showed that the co-expression of CXCR4 and IL10 increased the homing of MSCs into inflamed pads and induced an enhanced anti-inflammatory effect, compared to wild-type MSCs. Conclusions Our results demonstrate that the transient co-expression of CXCR4 and IL10 enhances the therapeutic potential of MSCs in a local inflammation mouse model, suggesting that these mRNA-modified cells may constitute a new step in the development of more efficient cell therapies for the treatment of inflammatory diseasesThis work was supported by the following public grants: Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III Ministerio de Ciencia, Innovación y Universidades and Fondo Europeo de Desarrollo Regional (FEDER) ((RETICS-RD16/0011/0011, PIE15/00048, PI18-01379), and Dirección General de Investigación de la Comunidad de Madrid (AvanCell-CM; Ref S2017/BMD-3692