Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disorder with a prominent genetic component. Individuals of African ancestry (AA) experience the disease more severely and with an increased co-morbidity burden compared to European ancestry (EA) populations. We hypothesize that the disparities in disease prevalence, activity, and response to standard medications between AA and EA populations is partially conferred by genomic influences on biological pathways. To address this, we applied a comprehensive approach to identify all genes predicted from SNP-associated risk loci detected with the Immunochip. By combining genes predicted via eQTL analysis, as well as those predicted from base-pair changes in intergenic enhancer sites, coding-region variants, and SNP-gene proximity, we were able to identify 1,731 potential ancestry-specific and trans-ancestry genetic drivers of SLE. Gene associations were linked to upstream and downstream regulators using connectivity mapping, and predicted biological pathways were mined for candidate drug targets. Examination of trans-ancestral pathways reflect the well-defined role for interferons in SLE and revealed pathways associated with tissue repair and remodeling. EA-dominant genetic drivers were more often associated with innate immune and myeloid cell function pathways, whereas AA-dominant pathways mirror clinical findings in AA subjects, suggesting disease progression is driven by aberrant B cell activity accompanied by ER stress and metabolic dysfunction. Finally, potential ancestry-specific and non-specific drug candidates were identified. The integration of all SLE SNP-predicted genes into functional pathways revealed critical molecular pathways representative of each population, underscoring the influence of ancestry on disease mechanism and also providing key insight for therapeutic selection.
versus 5.2% (P ¼ .02), MALE was noted in 12.2% versus 11.1% (P ¼ .25) and amputation rates were 5.2% versus 4.9% (P ¼ .53). When only high clinical risk patients were considered (n ¼ 4019), MACE was experienced in 7.3% versus 9.9% (P ¼ .003), MALE by 10.9% versus 10.3% (P ¼ .54) and amputation by 5.6% versus 5.1% (P ¼ .53). After inverse probability weighting, comparing the IEI to the reference LEB, MALE (adjusted odds ratio [AOR], 1.06; 95% confidence interval [CI], 0.94-1.20), MACE (AOR, 0.64; 95% CI, 0.54-0.76), and major amputation (AOR, 1.1; 95% CI, 0.95-1.3).Conclusions: Endovascular outcomes no longer demonstrate inferiority in MALE or major amputation. Endovascular intervention has a significantly reduced incidence of MACE. These results demonstrate an improvement in endovascular MACE, MALE and amputation rates in recent years relative to surgical bypass.
Diversity, equity, and inclusion represent interconnected goals meant to ensure that all individuals, regardless of their innate identity characteristics, feel welcomed and valued among their peers. Equity is achieved when all individuals have equal access to leadership and career advancement opportunities as well as fair compensation for their work. It is well-known that the unique backgrounds and perspectives contributed by a diverse workforce strengthen and improve medical organizations overall. The Society for Vascular Surgery (SVS) is committed to supporting the highest quality leadership, patient care, surgical education, and societal recommendations through promoting diversity, equity, and inclusion within the SVS. The overarching goal of this document is to provide specific context and guidance for enhancing diversity, equity, and inclusion within the SVS as well as setting the tone for conduct and processes beyond the SVS, within other national and regional vascular surgery organizations and practice settings.
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