A Virtual National Diversity Mentoring Initiative to Promote Inclusion in Emergency Medicine.

INTRODUCTION: Trainees underrepresented in medicine (URiM) face additional challenges seeking community in predominantly white academic spaces, as they juggle the effects of institutional, interpersonal, and internalized racism while undergoing medical training. To offer support and a space to share these unique experiences, mentorship for URiM trainees is essential. However, URiM trainees have limited access to mentorship from URiM faculty. To address this gap, we developed a national virtual mentoring program that paired URiM trainees interested in emergency medicine (EM) with experienced mentors. METHODS: We describe the implementation of a virtual Diversity Mentoring Initiative (DMI) geared toward supporting URiM trainees interested in EM. The program development involved 1) partnering of national EM organizations to obtain funding; (2) identifying a comprehensive platform to facilitate participant communication, artificial intelligence-enabled matching, and ongoing data collection; 3) focusing on targeted recruitment of URiM trainees; and (4) fostering regular leadership meeting cadence to customize the platform and optimize the mentorship experience. CONCLUSION: We found that by using a virtual platform, the DMI enhanced the efficiency of mentor-mentee pairing, tailored matches based on participants' interests and the bandwidth of mentors, and successfully established cross-institutional connections to support the mentorship needs of URiM trainees.

Signal transduction inhibitors in treatment of myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) are a group of hematologic disorders characterized by ineffective hematopoiesis that results in reduced blood counts. Although MDS can transform into leukemia, most of the morbidity experienced by these patients is due to chronically low blood counts. Conventional cytotoxic agents used to treat MDS have yielded some encouraging results but are characterized by many adverse effects in the predominantly elderly patient population. Targeted interventions aimed at reversing the bone marrow failure and increasing the peripheral blood counts would be advantageous in this cohort of patients. Studies have demonstrated over-activated signaling of myelo-suppressive cytokines such as TGF-ß, TNF-α and Interferons in MDS hematopoietic stem cells. Targeting these signaling cascades could be potentially therapeutic in MDS. The p38 MAP kinase pathway, which is constitutively activated in MDS, is an example of cytokine stimulated kinase that promotes aberrant apoptosis of stem and progenitor cells in MDS. ARRY-614 and SCIO-469 are p38 MAPK inhibitors that have been used in clinical trials and have shown activity in a subset of MDS patients. TGF-ß signaling has been therapeutically targeted by small molecule inhibitor of the TGF-ß receptor kinase, LY-2157299, with encouraging preclinical results. Apart from TGF-ß receptor kinase inhibition, members of TGF-ß super family and BMP ligands have also been targeted by ligand trap compounds like Sotatercept (ACE-011) and ACE-536. The multikinase inhibitor, ON-01910.Na (Rigosertib) has demonstrated early signs of efficacy in reducing the percentage of leukemic blasts and is in advanced stages of clinical testing. Temsirolimus, Deforolimus and other mTOR inhibitors are being tested in clinical trials and have shown preclinical efficacy in CMML. EGF receptor inhibitors, Erlotinib and Gefitinib have shown efficacy in small trials that may be related to off target effects. Cell cycle regulator inhibitors such as Farnesyl transferase inhibitors (Tipifarnib, Lonafarnib) and MEK inhibitor (GSK1120212) have shown acceptable toxicity profiles in small studies and efforts are underway to select mutational subgroups of MDS and AML that may benefit from these inhibitors. Altogether, these studies show that targeting various signal transduction pathways that regulate hematopoiesis offers promising therapeutic potential in this disease. Future studies in combination with high resolution correlative studies will clarify the subgroup specific efficacies of these agents.