While community‐weighted means of plant traits have been linked to mean environmental conditions at large scales, the drivers of trait variation within communities are not well understood. Local environmental heterogeneity (such as microclimate variability), in addition to mean environmental conditions, may decrease the strength of environmental filtering and explain why communities support different amounts of trait variation. Here, we assess two hypotheses: first, that more heterogeneous local environments and second, that less extreme environments, should support a broader range of plant strategies and thus higher trait variation. We quantified drivers of trait variation across a range of environmental conditions and spatial scales ranging from sub‐meter to tens of kilometers in montane and alpine plant communities. We found that, within communities, both environmental heterogeneity and environmental means are drivers of trait variation. However, the importance of each environmental factor varied depending on the trait. Our results indicate that larger‐scale trait–climate linkages that hold across communities also apply at small spatial scales, suggesting that microclimate variation within communities is a key driver of community functional diversity. Microclimatic variation provides a potential mechanism for helping to maintain diversity in local communities and also suggests that small‐scale environmental heterogeneity should be measured as a better predictor of functional diversity.

IMPORTANCE Burnout is a highly prevalent issue among medical trainees, but there has been limited research characterizing burnout specifically among medical students from groups who are underrepresented in medicine (URIM).OBJECTIVE To assess the association between components of the medical school learning environment and burnout among medical students who are URIM vs those who are not. DESIGN, SETTING, AND PARTICIPANTSThis retrospective cross-sectional survey study evaluated responses of allopathic medical students graduating from all US allopathic medical schools in 2016 and 2017 to the American Medical Colleges Graduation Questionnaire. Analysis was completed

Warm autoimmune hemolytic anemia (AIHA) is a hematologic disorder with an incidence of 1-3 per 10 5 individuals/year. Patients with systemic lupus erythematosus (SLE) develop AIHA in 3% of adult cases and 14% of pediatric cases. We report a case of AIHA refractory to multiple lines of treatment in a patient with SLE, who eventually responded to a proteasome inhibitor-based combination. A patient with systemic lupus erythematous was diagnosed with symptomatic autoimmune hemolytic anemia. The patient was refractory to multiple lines of treatment including prednisone, intravenous immune globulin, methylprednisolone, rituximab, cyclophosphamide, mycophenolate mofetil, and splenectomy. She eventually had a beneficial response to a proteasome inhibitor-based combination with bortezomib plus mycophenolate mofetil. The treatment of refractory autoimmune hemolytic anemia can be challenging. Patients with AIHA refractory to primary or secondary treatments must resort to receiving novel therapeutic modalities including combinations targeting plasma cell, T-and B-cell proliferation. K E Y W O R D S autoimmune hemolytic anemia, proteasome inhibitor, systemic lupus erythematosus How to cite this article: Crawford LR, Neparidze N. Refractory autoimmune hemolytic anemia in a systemic lupus erythematosus patient: A clinical case report.

Introduction: Multiple myeloma (MM) is an incurable yet highly heterogeneous disease of clonal plasma cells. The role of induction therapy is to achieve a complete response, thereby reducing the number of malignant plasma cells in the bone marrow. Partial responses or less are considered suboptimal and are associated with poorer outcomes. Following the approval of monoclonal antibody (mAb) therapies in MM, little is known of their effect on primary refractory and suboptimal responses in real-world populations. Methods: This retrospective cohort study included patients with clinical MM who were diagnosed and treated within the Yale New Haven Health System between 2009-2019. Our primary aim was to evaluate the overall survival (OS) in patients with primary refractory (PriRef) or suboptimal responding disease compared to those who achieved at least a very good partial response (≥VGPR). PriRef disease was assessed following three months of induction therapy, and was defined as a partial response, stable disease, or progressive disease based on International Myeloma Working Group (IMWG) criteria. A stricter cutoff of less than a VGPR was chosen for our definition of PriRef, because deeper responses, including MRD-negative status, have demonstrated increasingly important prognostic value. Descriptive statistics and OS analysis were performed with 2-tailed contingency χ²-tests, t-tests, Kaplan Meier, and log-rank tests using GraphPad Prism v8. Results: 246 patients (pts) with adequate response data following 3 months of induction therapy were identified. Clinical features included median age at diagnosis of 61 years (range, 34-92), 26.8% of whom were 70 years or older, 54.9% male, 63.4% Caucasian, 24.3% Black or African American, and 11% Hispanic. 46.8% had International Staging System (ISS) stage II or III disease and 41.1% had Revised International Staging System (R-ISS) stage II or III disease. 33.3% of patients had high-risk cytogenetics, which was defined as a del17/17p, t(4:14), t(4;16), t(4;20), gain or amplification of 1q, deletion of 1p, and chromosome 1 translocations. 81.7% of this cohort received a triplet or quadruplet induction regimen. The majority of patients received triplet induction regimens that included immunomodulatory and proteasome inhibitor combinations, and only two patients were prescribed quadruplet therapy. 44.7% of patients received autologous stem cell transplant (ASCT) at some point in their treatment course, with 79.1% (87/110) in the upfront setting and 20.9% (23/110) having delayed ASCT (Table 1). In this cohort, 122 pts (49.6%) achieved ≥VGPR and 124 pts (50.4%) were PriRef. There were no significant differences in the baseline demographics, ISS, R-ISS, or cytogenetic characteristics between ≥VGPR and PriRef. PriRef patients were less likely to have been treated with at least a triplet induction regimen than ≥VGPR (74.2% vs. 89.3%, p <0.01), and they were also less likely to have undergone ASCT (37.1% % vs. 52.5%, p = 0.02). When the two cohorts were stratified by upfront versus delayed ASCT, PriRef pts still demonstrated lower rates of ASCT in both settings, but the differences were not statistically significant (Table 1). There was no significant difference in OS between PriRef and ≥VGPR pts. Median OS for PriRef was 102.9 months compared to 114.9 months in ≥VGPR (p = 0.27) (Figure 1). Out of the 124 PriRef pts, 78 (62.9%) went on to receive subsequent lines of therapy. 39.7% of these PriRef pts received a mAb, such as daratumumab, elotuzumab or isatuximab, in the 2 nd or 3 rd line setting. When stratified by whether they received mAb therapy, median OS of PriRef pts who did not receive a mAb was 86.6 months, whereas median OS was not reached for the PriRef pts who received a mAb (p=0.98) (Figure 2). Conclusions: Our cohort analysis showed that early primary refractoriness to induction in newly diagnosed MM patients was not associated with a lower overall survival, despite lower utilization of triplet regimens and ASCT. Treatment with monoclonal antibodies in the 2 nd and 3 rd line setting may explain this finding. Since the approval of mAbs for myeloma, OS appears to be beneficially impacted. However, the effect of this class of therapy is yet to be fully appreciated in the real-world setting. Therefore, longer follow up data is needed to better assess the true impact of monoclonal antibodies on primary refractory multiple myeloma patients. Figure 1 Figure 1. Disclosures Neparidze: GlaxoSmithKline: Research Funding; Janssen: Research Funding; Eidos Therapeutics: Membership on an entity's Board of Directors or advisory committees.