CXCL10 deficiency limits macrophage infiltration, preserves lung matrix, and enables lung growth in bronchopulmonary dysplasia.

Preterm infants with oxygen supplementation are at high risk for bronchopulmonary dysplasia (BPD), a neonatal chronic lung disease. Inflammation with macrophage activation is central to the pathogenesis of BPD. CXCL10, a chemotactic and pro-inflammatory chemokine, is elevated in the lungs of infants evolving BPD and in hyperoxia-based BPD in mice. Here, we tested if CXCL10 deficiency preserves lung growth after neonatal hyperoxia by preventing macrophage activation. To this end, we exposed Cxcl10 knockout (Cxcl10-/-) and wild-type mice to an experimental model of hyperoxia (85% O2)-induced neonatal lung injury and subsequent regeneration. In addition, cultured primary human macrophages and murine macrophages (J744A.1) were treated with CXCL10 and/or CXCR3 antagonist. Our transcriptomic analysis identified CXCL10 as a central hub in the inflammatory network of neonatal mouse lungs after hyperoxia. Quantitative histomorphometric analysis revealed that Cxcl10-/- mice are in part protected from reduced alveolar. These findings were related to the preserved spatial distribution of elastic fibers, reduced collagen deposition, and protection from macrophage recruitment/infiltration to the lungs in Cxcl10-/- mice during acute injury and regeneration. Complimentary, studies with cultured human and murine macrophages showed that hyperoxia induces Cxcl10 expression that in turn triggers M1-like activation and migration of macrophages through CXCR3. Finally, we demonstrated a temporal increase of macrophage-related CXCL10 in the lungs of infants with BPD. In conclusion, our data demonstrate macrophage-derived CXCL10 in experimental and clinical BPD that drives macrophage chemotaxis through CXCR3, causing pro-fibrotic lung remodeling and arrest of alveolarization. Thus, targeting the CXCL10-CXCR3 axis could offer a new therapeutic avenue for BPD.

Características clínicas y evolución del reflujo vesicoureteral en la infancia / Clinical characteristics and outcome of childhood vesicoureteral reflux

Introducción. El objetivo fue evaluar las características clínicas y la evolución del reflujo vesicoureteral (RVU) según el sexo y grado de RVU.Población y métodos. Se incluyeron pacientes con RVU vistos durante el seguimiento de rutina entre enero de 2014 y enero de 2015. Se registraron las características demográficas, la evolución, los laboratorios y las imágenes.Resultados. Se seleccionó a 220 pacientes, cuya media de edad del diagnóstico era 3,17 ± 3,08 años; en ese momento, los varones eran menores que las niñas (2,00 ± 2,59 vs. 3,81 ± 3,15, p < 0,001). La infección urinaria fue la presentación más frecuente, seguida de hidronefrosis prenatal (HNP). El 22 % de los pacientes tuvo reflujo de grado 1-2; el 51 %, de grado 3; y el 27 %, de grado 4-5. En el reflujo de grado 4-5, las ecografías y gammagrafías con ácido dimercaptosuccínico (DMSA) marcado con 99mTc presentaron más anomalías, y se realizaron más cirugías (p < 0,001). En los varones, fueron más comunes el reflujo de grado 4-5 (43,6 % vs. 18,3 %) y las anomalías ecográficas (77 % vs. 54 %) y en la DMSA (77 % vs. 59 %) (p < 0,05). En las niñas, hubo mayores tasas de infección urinaria, disfunción de las vías urinarias inferiores y resolución espontánea (p < 0,05).Conclusiones. A pesar de la menor edad al momento del diagnóstico, la resolución espontánea fue menor en los varones, y estos presentaron HNP, reflujo grave y anomalías radiológicas más frecuentemente.

Introduction. The aim of the study was to assess the clinical features and outcome parameters of children with vesicoureteral reflux (VUR) based on gender and VUR grade.Population and methods. Patients with VUR who were seen during routine follow-up visits at Ankara University Children's Hospital between January 2014-January 2015 were included in this retrospective study. Patient demographics, clinical course, laboratory investigations, imaging were noted.Results. Two hundred and twenty patients were recruited. Mean age at the time of diagnosis was 3,17 ± 3,08 years. Boys were diagnosed at younger ages as compared to girls (2.00 ± 2,59 vs. 3,81 ± 3.15, p < 0.001). Urinary tract infection (UTI) was the most common presentation. The second presentation form was antenatal hydronephrosis (AHN) which was more common in males (25.6 %, p < 0.001). Twenty-two percent of the patients had grade 1-2, 51 % grade 3 and 27 % grade 4-5 reflux. Patients with grade 4-5 reflux had more abnormal ultrasound (US) and Tech 99m dimercaptosuccinic acid scintigraphy (DMSA) findings and surgery was performed more frequently in this group (p < 0.001). In males, grade 4-5 reflux (43.6 % vs. 18.3 %), abnormal US (77 % vs. 54 %) and DMSA (77 % vs. 59 %) findings were more frequent (p < 0.05). In girls higher rates of UTIs, lower urinary tract dysfunction (LUTD) and spontaneous reflux resolution were seen (p < 0.05).Conclusions: Despite younger age at diagnosis, spontaneous resolution was found lower in boys and they had more frequent AHN, more severe reflux, and radiological abnormalities.

Clinical characteristics and outcome of childhood vesicoureteral reflux. / Características clínicas y evolución del reflujo vesicoureteral en la infancia.

INTRODUCTION: The aim of the study was to assess the clinical features and outcome parameters of children with vesicoureteral reflux (VUR) based on gender and VUR grade. POPULATION AND METHODS: Patients with VUR who were seen during routine follow-up visits at Ankara University Children's Hospital between January 2014-January 2015 were included in this retrospective study. Patient demographics, clinical course, laboratory investigations, imaging were noted. RESULTS: Two hundred and twenty patients were recruited. Mean age at the time of diagnosis was 3,17 ± 3,08 years. Boys were diagnosed at younger ages as compared to girls (2.00 ± 2,59 vs. 3,81 ± 3.15, p < 0.001). Urinary tract infection (UTI) was the most common presentation. The second presentation form was antenatal hydronephrosis (AHN) which was more common in males (25.6 %, p < 0.001). Twenty-two percent of the patients had grade 1-2, 51 % grade 3 and 27 % grade 4-5 reflux. Patients with grade 4-5 reflux had more abnormal ultrasound (US) and Tech 99m dimercaptosuccinic acid scintigraphy (DMSA) findings and surgery was performed more frequently in this group (p < 0.001). In males, grade 4-5 reflux (43.6 % vs. 18.3 %), abnormal US (77 % vs. 54 %) and DMSA (77 % vs. 59 %) findings were more frequent (p < 0.05). In girls higher rates of UTIs, lower urinary tract dysfunction (LUTD) and spontaneous reflux resolution were seen (p < 0.05). CONCLUSIONS: Despite younger age at diagnosis, spontaneous resolution was found lower in boys and they had more frequent AHN, more severe reflux, and radiological abnormalities.

Introducción: El objetivo fue evaluar las características clínicas y la evolución del reflujo vesicoureteral (RVU) según el sexo y grado de RVU. Población y métodos: Se incluyeron pacientes con RVU vistos durante el seguimiento de rutina entre enero de 2014 y enero de 2015. Se registraron las características demográficas, la evolución, los laboratorios y las imágenes. Resultados: Se seleccionó a 220 pacientes, cuya media de edad del diagnóstico era 3,17 ± 3,08 años; en ese momento, los varones eran menores que las niñas (2,00 ± 2,59 vs. 3,81 ± 3,15, p < 0,001). La infección urinaria fue la presentación más frecuente, seguida de hidronefrosis prenatal (HNP). El 22 % de los pacientes tuvo reflujo de grado 1-2; el 51 %, de grado 3; y el 27 %, de grado 4-5. En el reflujo de grado 4-5, las ecografías y gammagrafías con ácido dimercaptosuccínico (DMSA) marcado con 99mTc presentaron más anomalías, y se realizaron más cirugías (p < 0,001). En los varones, fueron más comunes el reflujo de grado 4-5 (43,6 % vs. 18,3 %) y las anomalías ecográficas (77 % vs. 54 %) y en la DMSA (77 % vs. 59 %) (p < 0,05). En las niñas, hubo mayores tasas de infección urinaria, disfunción de las vías urinarias inferiores y resolución espontánea (p < 0,05). Conclusiones: A pesar de la menor edad al momento del diagnóstico, la resolución espontánea fue menor en los varones, y estos presentaron HNP, reflujo grave y anomalías radiológicas más frecuentemente.