Does crenolanib inhibit the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors?
Crenolanib is a potent inhibitor of imatinib-resistant PDGFRA kinases associated with GIST, including the PDGFRA D842V mutation found in approximately 5% of GISTs. The spectrum of activity of crenolanib suggests that this drug is a type I inhibitor (inhibitor of activated conformation of kinase). Based in part on these results, a phase II clinical study of this agent to treat GIST with the PDGFRA D842V mutation has been initiated.
Isolated eardrum perforation in survivors of explosions does not appear to be a marker of concealed pulmonary blast injury nor of a poor prognosis. Therefore, in a mass casualty event, persons who have sustained isolated eardrum perforation from explosions may safely be discharged from the emergency department after chest radiography and a brief observation period.