Patient-Family and Provider Partnerships in the Management of Pediatric Uncomplicated Appendicitis.

In recent years, studies have demonstrated non-operative management with antibiotics alone to be a safe and effective treatment option for children with uncomplicated acute appendicitis. Shared decision-making is critical in the treatment of uncomplicated appendicitis due to the markedly different risks and benefits associated with surgery and non-operative management. In this report, we discuss the importance of shared decision-making in surgery using a case of uncomplicated appendicitis as an example. We present both the patient-family and provider perspectives on evaluating and deciding between operative and non-operative management and discuss the value of shared decision-making in the unique setting of an acute pathologic process with surgical and medical treatment options.

EGFR transactivates RON to drive oncogenic crosstalk.

Crosstalk between different receptor tyrosine kinases (RTKs) is thought to drive oncogenic signaling and allow therapeutic escape. EGFR and RON are two such RTKs from different subfamilies, which engage in crosstalk through unknown mechanisms. We combined high-resolution imaging with biochemical and mutational studies to ask how EGFR and RON communicate. EGF stimulation promotes EGFR-dependent phosphorylation of RON, but ligand stimulation of RON does not trigger EGFR phosphorylation - arguing that crosstalk is unidirectional. Nanoscale imaging reveals association of EGFR and RON in common plasma membrane microdomains. Two-color single particle tracking captured formation of complexes between RON and EGF-bound EGFR. Our results further show that RON is a substrate for EGFR kinase, and that transactivation of RON requires formation of a signaling competent EGFR dimer. These results support a role for direct EGFR/RON interactions in propagating crosstalk, such that EGF-stimulated EGFR phosphorylates RON to activate RON-directed signaling.