Prognostic Value of Hospital Frailty Risk Score and Clinical Outcomes in Patients Undergoing Revascularization for Critical Limb-Threatening Ischemia.

Background The impact of medical record-based frailty assessment on clinical outcomes in patients undergoing revascularization for critical limb-threatening ischemia (CLTI) is unknown. Methods and Results This study included patients with CLTI aged ≥18 years from the nationwide readmissions database 2016 to 2018 who underwent endovascular revascularization (ER) or surgical revascularization (SR). The hospital frailty risk score, a previously validated International Classification of Diseases, Tenth Edition, Clinical Modification (ICD-10-CM) claims-based score, was used to categorize patients into low- (<5), intermediate- (5-15), and high-risk (>15) frailty categories. Primary outcomes were in-hospital mortality and major amputation at 6 months. A total of 64 338 patients were identified who underwent ER (82.3%) or SR (17.7%) for CLTI. The mean (SD) age of the cohort was 69.3 (11.8) years, and 63% of patients were male. This study found a nonlinear association between hospital frailty risk score and in-hospital mortality and 6-month major amputation. In both ER and SR cohorts, the intermediate- and high-risk groups were associated with a significantly higher risk of in-hospital mortality (high-risk group: ER: odds ratio [OR], 7.2 [95% CI, 4.4-11.6], P<0.001; SR: OR, 28.6 [95% CI, 3.4-237.6], P=0.002) and major amputation at 6 months (high-risk group: ER: hazard ratio [HR], 1.6 [95% CI, 1.5-1.7], P<0.001; SR: HR, 1.7 [95% CI, 1.4-2.2], P<0.001) compared with the low-risk group. Conclusions The hospital frailty risk score, generated from the medical record, can identify frailty and predict in-hospital mortality and 6-month major amputation in patients undergoing ER or SR for CLTI. Further studies are needed to assess if this score can be incorporated into clinical decision-making in patients undergoing revascularization for CLTI.

Transient exposure to elastase induces mouse aortic wall smooth muscle cell production of MCP-1 and RANTES during development of experimental aortic aneurysm.

PURPOSE: Abdominal aortic aneurysm (AAA) is associated with chronic transmural inflammation and destruction of the elastic media. The purpose of this study was to elucidate molecular mechanisms that might orchestrate leukocyte recruitment into the outer aortic wall by determining whether CC chemokines contribute to development of aneurysm degeneration in an elastase-induced mouse model of AAA. METHODS: Adult male C57BL/6J mice underwent transient elastase perfusion of the abdominal aorta to induce development of AAA. At various intervals after elastase perfusion (0, 4, 7, 14 days), real-time reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays were used to measure aortic wall expression of the CC (beta) chemokines, monocyte chemoattractant protein-1 (MCP-1) and regulated on activation, normal T-cell expressed and secreted (RANTES). Expression of these chemokines by cultured mouse aortic smooth muscle cells (AoSMC) was similarly assessed after transient (5 minutes) exposure to elastase solutions in vitro. RESULTS: Mouse aortic diameter (mean +/- SEM) increased to aneurysmal proportions by 14 days after elastase perfusion (from 0.51 +/- 0.03 mm to 1.34 +/- 0.32 mm; 163% increase; P <.05), with macrophage infiltration of the outer aortic wall beginning within 7 to 10 days. Increased aortic wall messenger RNA expression for MCP-1 (28-fold) and RANTES (11-fold) was observed on day 4, with maximal production of chemokine protein on day 7 (MCP-1, from 7.07 +/- 0.06 ng/mL to 19.60 +/- 0.19 ng/mL; P <.001; RANTES, from 0.23 +/- 0.006 ng/mL to 2.03 +/- 0.057 ng/mL; P <.001). Neither MCP-1 nor RANTES was detected in normal mouse aorta with immunohistochemistry, but both chemokines were abundant in AAA. Within 48 hours of transient exposure to elastase, cultured mouse AoSMC exhibited pronounced induction (>90-fold) of MCP-1 and RANTES, despite concomitant decrease in cell numbers. CONCLUSIONS: Increased mouse aortic wall expression of MCP-1 and RANTES occurs early in development of elastase-induced AAA and before onset of the chronic inflammatory response. Moreover, elastase directly stimulates AoSMC chemokine production in vitro. Elastase-induced medial SMC production of CC chemokines may therefore provide an important link between enzymatic injury, leukocyte recruitment, and aneurysmal degeneration of the aortic wall.

Secondary aortoesophageal fistula after endoluminal exclusion because of thoracic aortic transection.

Secondary aortoesophageal fistula (AEF) is a rare but catastrophic complication that occurs after thoracic aortic reconstruction. Recently endoluminal stent grafts have been used in selected patients with a thoracic aortic aneurysm, dissection, or traumatic aortic transection. A 24-year-old woman had massive upper gastrointestinal tract bleeding 15 months after endoluminal stent graft placement because of traumatic descending thoracic aortic transection. Evaluation demonstrated an AEF from the mid-esophagus to the endoluminal stent graft. The endoluminal graft was explanted, with primary repair of the thoracic aortic defect and simultaneous primary repair of the esophageal injury. The patient is well 15 months after open repair of the AEF.

Monocyte chemotactic activity in human abdominal aortic aneurysms: role of elastin degradation peptides and the 67-kD cell surface elastin receptor.

BACKGROUND: Chronic inflammation is a characteristic feature of abdominal aortic aneurysms (AAAs), but the molecular signals responsible for recruiting monocytes into the outer aortic wall are unresolved. The purpose of this study was to examine whether AAA tissues elaborate chemotactic activity for mononuclear phagocytes and to determine whether this activity is attributable to interactions between elastin degradation peptides (EDPs) and their cell surface receptor, the 67-kD elastin binding protein (EBP). MATERIAL AND METHODS: Soluble proteins were extracted from human AAA tissues, and chemotactic activity for differentiated U937 mononuclear phagocytes was measured by use of a modified Boyden chamber. Chemotactic activity induced by N -formyl-Met-Leu-Phe was used as a positive control and checkerboard analysis was used to distinguish chemotaxis from chemokinesis. Inhibition of chemotaxis was tested by peptide competition, blocking antibodies and galactosugar-mediated dissociation of the 67-kD EBP. RESULTS: AAA extracts stimulated a concentration-dependent increase in monocyte migration that reached up to 24% of the maximal effect induced by N -formyl-Met-Leu-Phe. Checkerboard analysis demonstrated that AAA extracts stimulated chemotaxis without a chemokinetic effect. AAA-derived chemotactic activity was eliminated by competition with Val-Gly-Val-Arg-Pro-Gly (VGVAPG), a repetitive peptide found in human elastin that binds to cellular elastin receptors, and decreased nearly 40% in the presence of BA-4, an antielastin monoclonal antibody that can block EDP-mediated chemotactic activity. Monocyte chemotaxis in response to both VGVAPG and AAA extracts was abolished in the presence of lactose, a galactosugar that specifically dissociates the 67-kD EBP, but it was unaffected by either glucose, fructose, or mannose. CONCLUSIONS: These findings indicate that soluble EDPs released within human AAA tissue can subsequently attract mononuclear phagocytes through ligand-receptor interactions with the 67-kD EBP, thereby providing a plausible molecular mechanism to explain the inflammatory response that accompanies aneurysmal degeneration. Better understanding of factors regulating inflammatory cell recruitment may lead to novel forms of therapy for early stages of aneurysmal degeneration.