RESUMO
BACKGROUND: Epidemiological data on paediatric acute kidney injury (AKI) in sub-Saharan Africa are limited and largely retrospective. We performed a prospective study of AKI among patients admitted through the emergency room. METHODS: Children admitted to the post-neonatal emergency room of the University College Hospital, Ibadan, Nigeria between February 2016 and January 2017 were studied. AKI was defined by Kidney Disease: Improving Global Outcomes serum creatinine criteria. AKI ascertainment relied on serum creatinine measurements carried out in routine care by post-admission Day 1. We compared in-hospital mortality by post-admission Day 7 for patients with and without AKI (no-AKI). RESULTS: Of the 1344 children admitted to the emergency room, 331 were included in the study. AKI occurred in 112 patients (33.8%) with a median age of 3.1 years [interquartile range (IQR) 0.9-9.4] and was Stage 3 in 50.5% of the cases. The no-AKI group had a median age of 1.8 (IQR 0.7-5.8) years. The underlying diagnoses in patients with AKI were sepsis (33.0%), malaria (12.5%) and primary renal disorders (13.4%). Twenty-four of the patients with AKI underwent dialysis: haemodialysis in 20 and peritoneal dialysis in 4. By Day 7 of admission, 7 of 98 (7.1%) patients in the AKI group had died compared with 5 of 175 (2.9%) patients in the no-AKI group [odds ratio 2.6 (95% confidence interval 0.8-8.5)]. Outcome data were not available for 58 (17.5%) patients. CONCLUSIONS: AKI is common among paediatric emergency room admissions in a tertiary care hospital in sub-Saharan Africa. It is associated with high mortality risk that may be worse in settings without dialysis.
RESUMO
Recently platelet derived growth factor receptor-alpha (PDGFRα) was recognized as a potential target to treat aggressive papillary thyroid cancer given its strong association with lymph node metastases. However, it is unclear how PDGFRα potentiates metastases and if it works through the canonical MAPK pathway traditionally linked to PTC oncogenesis. We explored the phenotypic changes driven by PDGFRα activation in human papillary thyroid cancer (PTC) cells and the downstream signalling cascades through which they are effected. We demonstrate that PDGFRα drives an impressive phenotypic change in PTC cell lines as documented by significant cytoskeletal rearrangement, increased migratory potential, and the formation of invadopodia. Cells lacking PDGFRα formed compact and dense spheroids, whereas cells expressing active PDGFRα exhibited invadopodia in three-dimensional culture. To achieve this, active PDGFRα provoked downstream activation of the MAPK/Erk, PI3K/Akt and STAT3 pathways. We further confirmed the role of PDGFRα as a transformative agent promoting the epithelial to mesenchymal transition of PTC cells, through the augmentation of Snail and Slug expression. Crenolanib, a small molecule inhibitor of PDGFRα, suppressed the levels of Snail and Slug and almost completely reversed all the phenotypic changes. We demonstrate that PDGFRα activation is an essential component that drives aggressiveness in PTC cells, and that the signaling pathways are complex, involving not only the MAPK/Erk but also the PI3K/Akt and STAT3 pathways. This argues for upstream targeting of the PDGFRα given the redundancy of oncogenic pathways in PTC, especially in patients whose tumors over-express this tyrosine kinase receptor.
