Trends and disparities in cardiovascular deaths in systemic lupus erythematosus: A population-based retrospective study in the United States from 1999 to 2020.

PURPOSE: This study aimed to analyze two decades of consecutive mortality data to investigate cardiovascular deaths in Systemic Lupus Erythematosus (SLE) across the United States (US), identifying patterns and disparities in mortality rates. METHODS: A retrospective analysis was conducted using mortality data from the CDC WONDER database spanning 1999-2020. ICD-10 codes for diseases of circulatory system (I00-I99) and for SLE (M32) were used to identify cardiovascular-related deaths in SLE among adults aged 25 years and older at the time of death. Age-adjusted mortality rates (AAMRs) per 1,000,000 persons were calculated, and trends were assessed using Average Annual Percentage Change (AAPC) and Annual Percent Change (APC) using Joinpoint. Data were stratified by year, sex, race/ethnicity, and geographical regions. RESULTS: Between 1999 and 2020, cardiovascular-related deaths in SLE accounted for 6,548 deaths among adults aged 25 and older in the US. The overall AAMR for cardiovascular-related deaths in SLE decreased from 1.81 in 1999 to 1.53 in 2020, with an AAPC of -1.00 (95% CI: -1.91 to -0.24, p=0.025). A significant decline occurred from 1999 to 2014 with an APC of -3.20 (95% CI: -5.56 to -2.18; p=0.02), followed by a notable increase of 4.73 (95% CI: 0.41 to 18.29, p=0.23) from 2014 to 2020. Women exhibited higher AAMRs compared to men (women: 2.12, men: 0.53). The AAMR decreased for both men and women, with a steeper decline for men from 1999 to 2014 (APC: -4.85 95% CI: -15.58 to -2.62; p<0.02) compared to women in the same period (APC: -2.81 95% CI: -5.78 to -1.73; p<0.03). The Black cohort had a higher AAMR (3.54 95% CI: 3.37 to 3.70), compared to the White cohort (1.12 95% CI: 1.09 to 1.16). The highest mortality was in the Western region (AAMR: 1.60 95% CI: 1.52 to 1.68). Geographically, AAMRs ranged from 0.62 in Massachusetts to 3.11 in Oklahoma. Metropolitan areas had higher AAMRs than Non-metropolitan areas [(1.41 95% CI: 1.37 to 1.45) vs (1.29 95% CI: 1.21 to 1.37)], with a significant mortality reduction in Metropolitan area from 1999-2020 (AAPC: -1.04 95% CI: -1.95 to -0.28, p=0.0064) compared to Non-metropolitan areas in the same time frame (AAPC: -0.86, 95% CI: -2.43 to 0.33 p=0.152). CONCLUSIONS: This analysis highlights notable differences in mortality rates related to cardiovascular deaths in SLE. The target population was adult patients aged 25 and older in the United States. These results are based on demographic and geographic factors. Initially, there was a considerable decrease, but recently the mortality rates have started to rise. This highlights the importance of patient focused interventions to address disparities and improve health outcomes.

Mos1 Element-Mediated CRISPR Integration of Transgenes in Caenorhabditis elegans.

The introduction of exogenous genes in single-copy at precise genomic locations is a powerful tool that has been widely used in the model organism Caenorhabditis elegans Here, we have streamlined the process by creating a rapid, cloning-free method of single-copy transgene insertion we call Mos1 element-mediated CRISPR integration (mmCRISPi). The protocol combines the impact of Mos1 mediated single-copy gene insertion (mosSCI) with the ease of CRISPR/Cas9 mediated gene editing, allowing in vivo construction of transgenes from linear DNA fragments integrated at defined loci in the C. elegans genome. This approach was validated by defining its efficiency at different integration sites in the genome and by testing transgene insert size. The mmCRISPi method benefits from in vivo recombination of overlapping PCR fragments, allowing researchers to mix-and-match between promoters, protein-coding sequences, and 3' untranslated regions, all inserted in a single step at a defined Mos1 loci.