Sarcomas are rare but highly aggressive mesenchymal tumors with a median survival of 10–18 months for metastatic disease. Mutation and/or overexpression of many receptor tyrosine kinases (RTKs) including c-Met, PDGFR, c-Kit and IGF1-R drive defective signaling pathways in sarcomas. MGCD516 (Sitravatinib) is a novel small molecule inhibitor targeting multiple RTKs involved in driving sarcoma cell growth. In the present study, we evaluated the efficacy of MGCD516 both in vitro and in mouse xenograft models in vivo. MGCD516 treatment resulted in significant blockade of phosphorylation of potential driver RTKs and induced potent anti-proliferative effects in vitro. Furthermore, MGCD516 treatment of tumor xenografts in vivo resulted in significant suppression of tumor growth. Efficacy of MGCD516 was superior to imatinib and crizotinib, two other well-studied multi-kinase inhibitors with overlapping target specificities, both in vitro and in vivo. This is the first report describing MGCD516 as a potent multi-kinase inhibitor in different models of sarcoma, superior to imatinib and crizotinib. Results from this study showing blockade of multiple driver signaling pathways provides a rationale for further clinical development of MGCD516 for the treatment of patients with soft-tissue sarcoma.

Although several interventions resulted in improved child development outcomes for children aged 0 to 3 years, comparison across studies and interventions is limited by use of different outcome measures, time of evaluation, and variability of results.

Immune alterations in MDS are complex, heterogeneous, and intertwined with clonal hematopoiesis and stromal cell dysfunction. Inflammation in MDS proceeds as a vicious cycle, mediated in large part by secreted factors, which induce cell death and activate innate immune signaling. Therapeutic targeting of this variable immune dysregulation has led to modest responses thus far, but incorporation of the growing repertoire of immunotherapy brings new potential for improved outcomes. The immune milieu is variable across the spectrum of MDS subtypes, with a changing balance of inflammatory and suppressive cellular forces from low- to high-risk disease.

In recent years there has been increasing emphasis on active and engaged learning in medical education. The purpose of this study was to determine medical student satisfaction and performance in a module where 44% of the educational time was spent in a combination of large group engaged learning sessions and at-home modules. Methods: Over two years a week-long dermatology course was transitioned to a format that included numerous large group interactive sessions. Course satisfaction results, exam performance, and a questionnaire on engaged learning were assessed. Results: Overall course satisfaction improved from 94% to 99% of students ranking the course as good or excellent as did the percent of students who rated lecture delivery as engaging (88% to 98%). The percent of students responding that the module provided opportunities for collaboration among students rose from 50% to 92%. We took away a number of learning points from these sessions based on student feedback, including a need to be sensitive to the time required for pre-class learning modules and the format of such modules. Conclusions: Based on student feedback, we found that large group teaching was effective in fostering collaboration as well as improving self-reported comprehension and overall course satisfaction.