RESUMEN
OBJECTIVE: To evaluate associations between postnatal imaging features and outcome of left-sided congenital diaphragmatic hernia, as defined by overall survival and a requirement for extracorporeal membrane oxygenation (ECMO). STUDY DESIGN: Newborns diagnosed prenatally with left-sided congenital diaphragmatic hernia between January 2013 and September 2021 were studied retrospectively. The esophageal deviation index was newly defined as the largest diameter from the midline to deviated gastric tube divided by the largest transverse diameter of the thoracic cavity on the radiograph. Regression analyses were performed to identify postnatal imaging features associated with overall survival and a requirement for ECMO. The predictive power (ie, area under the curve [AUC] of a time-dependent receiver operating characteristic curve) of prenatal, postnatal, and intraoperative findings for predicting survival were calculated. RESULTS: Ninety-seven patients (54 males; mean gestational age, 38.3 ± 1.9 weeks; mean birth weight, 2956.5 ± 540.0 g) were analyzed. The esophageal deviation index (adjusted hazard ratio [HR], moderate [≥0.19 to <0.24], 6.427 [P = .029]; severe [≥0.24], 33.007 [P < .001]) and right pneumothorax (adjusted HR, 8.763; P = .002) were associated with overall survival and with a requirement for ECMO. Liver herniation on postnatal ultrasound also was associated with overall survival (P < .001) and need for ECMO (P = .001). In addition, the AUC for prediction of 1-year survival from postnatal ultrasound was comparable with that of prenatally or intraoperatively detected liver herniation (0.93; 95% CI, 0.88-0.97). CONCLUSIONS: The esophageal deviation index, right pneumothorax, and liver herniation observed by postnatal imaging have prognostic value in patients with left-sided congenital diaphragmatic hernia.
Asunto(s)
Hernias Diafragmáticas Congénitas , Neumotórax , Embarazo , Masculino , Femenino , Humanos , Recién Nacido , Lactante , Hernias Diafragmáticas Congénitas/diagnóstico por imagen , Hernias Diafragmáticas Congénitas/cirugía , Estudios Retrospectivos , Ultrasonografía Prenatal/métodos , Hígado/diagnóstico por imagenRESUMEN
Nek2 (NIMA-related kinase 2) is a serine/threonine-protein kinase that localizes to centrosomes and kinetochores, controlling centrosome separation, chromosome attachments to kinetochores, and the spindle assembly checkpoint. These processes prevent centrosome amplification (CA), mitotic dysfunction, and chromosome instability (CIN). Our group and others have suggested that Nek2 maintains high levels of CA/CIN, tumor growth, and drug resistance. We identified that Nek2 overexpression correlates with poor survival of breast cancer. However, the mechanisms driving these phenotypes are unknown. We now report that overexpression of Nek2 in MCF10A cells drives CA/CIN and aneuploidy. Besides, enhanced levels of Nek2 results in larger 3D acinar structures, but could not initiate tumors in a p53+/+ or a p53-/- xenograft model. Nek2 overexpression induced the epithelial-to-mesenchymal transition (EMT) while its downregulation reduced the expression of the mesenchymal marker vimentin. Furthermore, either siRNA-mediated downregulation or INH6's chemical inhibition of Nek2 in MDA-MB-231 and Hs578t cells showed important EMT changes and decreased invasion and migration. We also showed that Slug and Zeb1 are involved in Nek2 mediated EMT, invasion, and migration. Besides its role in CA/CIN, Nek2 contributes to breast cancer progression through a novel EMT mediated mechanism.