634 Assessing the effects of systemic therapy for vascular malformations using RNAseq

Vascular malformations due to somatic mutation result in abnormal development of endothelial network. The disorder can associate with pain, ulceration, bleeding, recurrent infection, disfigurement, and organ dysfunction. Though surgical interventions including debulking, excision sclerotherapy have shown some success, recurrence disease progression are frequent. Complex cases often not amendable associated risks. FDA-approved medical treatment is yet be developed for these lesions. Following the serendipitous discovery benefit using sildenafil lymphatic (LM), a multicenter trial showed that clinical improvements were experienced by many patients regardless percentage volumetric reduction noted. This has expanded investigational drug repertoire malformations. More recently, sirolimus become most frequently used agent variety vascular anomalies its antiproliferative, antiangiogenic perhaps anti-inflammatory properties. To date, exact mechanism action or this context remains elucidated. In study, we investigated differential transcriptional signature blood from before after sirolimus. addition, compared changes peripheral radiological improvement measured as volume via magnetic resonance imaging (MRI). Our results show drugs distinct well overlapping effects on signatures, profiling cell proliferation, systemic inflammation, overall outcomes. Taken together, study delineates molecular medications been off label practice. approach our may also expedite therapeutic discoveries; enable noninvasive diagnosis optimization.