Resolution of inflammation via RvD1/FPR2 signaling mitigates Nox2 activation and ferroptosis of macrophages in experimental abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) formation is characterized by inflammation, leukocyte infiltration, and vascular remodeling. Resolvin D1 (RvD1) is derived from ω-3 polyunsaturated fatty acids and is involved in the resolution phase of chronic inflammatory diseases. The aim of this study was to decipher the protective role of RvD1 via formyl peptide receptor 2 (FPR2) receptor signaling in attenuating abdominal aortic aneurysms (AAA). The elastase-treatment model of AAA in C57BL/6 (WT) mice and human AAA tissue was used to confirm our hypotheses. Elastase-treated FPR2-/- mice had a significant increase in aortic diameter, proinflammatory cytokine production, immune cell infiltration (macrophages and neutrophils), elastic fiber disruption, and decrease in smooth muscle cell α-actin expression compared to elastase-treated WT mice. RvD1 treatment attenuated AAA formation, aortic inflammation, and vascular remodeling in WT mice, but not in FPR2-/- mice. Importantly, human AAA tissue demonstrated significantly decreased FPR2 mRNA expression compared to non-aneurysm human aortas. Mechanistically, RvD1/FPR2 signaling mitigated p47phox phosphorylation and prevented hallmarks of ferroptosis, such as lipid peroxidation and Nrf2 translocation, thereby attenuating HMGB1 secretion. Collectively, this study demonstrates RvD1-mediated immunomodulation of FPR2 signaling on macrophages to mitigate ferroptosis and HMGB1 release, leading to resolution of aortic inflammation and remodeling during AAA pathogenesis.

Resolvin D2/GPR18 signaling enhances monocytic myeloid-derived suppressor cell function to mitigate abdominal aortic aneurysm formation.

Abdominal aortic aneurysm (AAA) formation is a chronic vascular pathology characterized by inflammation, leukocyte infiltration and vascular remodeling. The aim of this study was to delineate the protective role of Resolvin D2 (RvD2), a bioactive isoform of specialized proresolving lipid mediators, via G-protein coupled receptor 18 (GPR18) receptor signaling in attenuating AAAs. Importantly, RvD2 and GPR18 levels were significantly decreased in aortic tissue of AAA patients compared with controls. Furthermore, using an established murine model of AAA in C57BL/6 (WT) mice, we observed that treatment with RvD2 significantly attenuated aortic diameter, pro-inflammatory cytokine production, immune cell infiltration (neutrophils and macrophages), elastic fiber disruption and increased smooth muscle cell α-actin expression as well as increased TGF-ß2 and IL-10 expressions compared to untreated mice. Moreover, the RvD2-mediated protection from vascular remodeling and AAA formation was blocked when mice were previously treated with siRNA for GPR18 signifying the importance of RvD2/GPR18 signaling in vascular inflammation. Mechanistically, RvD2-mediated protection significantly enhanced infiltration and activation of monocytic myeloid-derived suppressor cells (M-MDSCs) by increasing TGF-ß2 and IL-10 secretions that mitigated smooth muscle cell activation in a GPR18-dependent manner to attenuate aortic inflammation and vascular remodeling via this intercellular crosstalk. Collectively, this study demonstrates RvD2 treatment induces an expansion of myeloid-lineage committed progenitors, such as M-MDSCs, and activates GPR18-dependent signaling to enhance TGF-ß2 and IL-10 secretion that contributes to resolution of aortic inflammation and remodeling during AAA formation.

Processing and Handling Cost of Single-use Versus Traditional Instrumentation for 1 Level Lumbar Fusions.

STUDY DESIGN: A single center, observational prospective clinical study. OBJECTIVE: The aim of this study was to compare the instrumentation-related cost and efficiency of single-use instrumentation versus traditional reusable instrument trays. SUMMARY OF BACKGROUND DATA: Single-use instrumentation provides the opportunity to reduce costs associated with cleaning and sterilizing instrumentation after surgery. Although previous studies have shown single-use instrumentation is effective in other orthopedic specialties, it is unclear if single-use instrumentation could provide economic advantages in spine surgery. MATERIALS AND METHODS: A total of 40 (20 reusable instrumentation and 20 single-use instrumentation) lumbar decompression (1-3 level) and fusion (1 level) spine surgeries were collected. Instrument handling, opening, setup, re-stocking, cleaning, sterilization, inspection, packaging, and storage were recorded by direct observation for both reusable and single-use instrumentation. The rate of infection was noted for each group. RESULTS: Mean time of handling instruments by the scrub nurse was 11.6 (±3.9) minutes for reusable instrumentation and 2.1 (±0.5) minutes for single-use instrumentation. Mean cost of handling reusable instruments was estimated to be $8.52 (±$2.96) per case, and the average cost to reprocess a single tray by Sterilization Processing Department (SPD) was $58. Thus, the median cost for sterilizing 2 reusable trays per case was $116, resulting in an average total Costresuable of $124.52 (±$2.96). Mean cost of handling single-use instrumentation was estimated to be $1.57 ($0.38) per case. CONCLUSION: Single-use instrumentation provided greater cost savings and reduced time from the opening of instrumentation to use in surgery when compared with reusable instrumentation.