Immune Modulation as a Treatment for Abdominal Aortic Aneurysms

In the United States, over 200,000 new patients are diagnosed with abdominal aortic aneurysm (AAA) each year. Consequently, over 40,000 highly morbid aortic reconstructions are performed each year to prevent aneurysm rupture, a catastrophic event associated with near-certain mortality. No pharmaceutical currently exists to slow aneurysm growth, but a 50% reduction in diameter growth per annum could halve the number of aortic reconstructions required. Therefore, successful use of cell therapy to modulate chronic inflammation hallmark to AAA to slow diameter expansion represents a potentially paradigm-altering treatment

Combined transbrachial and transfemoral strategy to deploy an iliac branch endoprosthesis in the setting of a pre-existing endovascular aortic aneurysm repair

This article describes brachial access to position a long sheath in the abdominal aorta in conjunction with a large caliber sheath via the femoral artery ipsilateral to the target site to deliver a 0.018 bodyfloss wire. This bodyfloss wire is inserted into the precannulation port of the iliac branch endoprosthesis (W. L. Gore and Associates, Flagstaff, Ariz), which is then advanced from the groin. Once the bifurcated device is deployed, hypogastric access and stenting is achieved from the upper extremity. This technique is an alternative to safely extend the distal seal while preserving the hypogastric artery and has the advantage of limited iliac bifurcation manipulation

Staged endovascular repair of an abdominal aortic aneurysm adjacent to a chronic high-flow iliocaval traumatic arteriovenous fistula

Large-vessel chronic traumatic arteriovenous fistulas are a rare complication after trauma. Delayed presentation can consist of one or more features of high-output cardiac failure, pulsatile abdominal mass, bruit, limb ischemia, and venous congestion. We describe a patient with a complex iliocaval fistula secondary to a remote gunshot wound associated with a large 8.5-cm aortic aneurysm. Informed consent of the patient was obtained for publication of the case

Aggressive Surveillance Is Needed to Detect Endoleaks and Junctional Separation between Device Components after Zenith Fenestrated Aortic Reconstruction

Background Junctional separation and resulting type IIIa endoleak is a well-known problem after EVAR (endovascular aneurysm repair). This complication results in sac pressurization, enlargement, and eventual rupture. In this manuscript, we review the incidence of this late finding in our experience with the Cook Zenith fenestrated endoprosthesis (ZFEN, Bloomington, IN). Methods A retrospective review was performed of a prospectively maintained institutional ZFEN fenestrated EVAR database capturing all ZFENs implanted at a large-volume, academic hospital system. Patients who experienced junctional separation between the fenestrated main body and distal bifurcated graft (with or without type IIIa endoleak) at any time after initial endoprosthesis implantation were subject to further evaluation of imaging and medical records to abstract clinical courses. Results In 110 ZFENs implanted from October 2012 to December 2017 followed for a mean of 1.5 years, we observed a 4.5% and 2.7% incidence of clinically significant junctional separation and type IIIa endoleak, respectively. Junctional separation was directly related to concurrent type Ib endoleak in all 5 patients. Three patients presented with sac enlargement. One patient did not demonstrate any evidence of clinically significant endoleak and had a decreasing sac size during follow-up imaging. The mean time to diagnosis of modular separation in these patients was 40 months. Junctional separation was captured in surveillance in 2 patients and reintervened upon before manifestation of endoleak. However, the remaining 3 patients completed modular separation resulting in rupture and emergent intervention in 2 and an aortic-related mortality in the other. Conclusions Junctional separation between the fenestrated main and distal bifurcated body with the potential for type IIIa endoleak is an established complication associated with the ZFEN platform. Therefore, we advocate for maximizing aortic overlap during the index procedure followed by aggressive surveillance and treatment of stent overlap loss captured on imaging

Diagnosis and management of the venous malformations of Klippel-Trénaunay syndrome

Objective A dearth of information exists in the literature regarding current practice in the management of Klippel-Trénaunay syndrome (KTS), a rare condition. We review and describe the etiology, diagnosis, and treatment of KTS. Methods Relevant data were synthesized from a Medline review using a combination of the keyterms “Klippel” and “Trénaunay.” The majority of hits described singular case reports and were subsequently excluded. The remaining papers were then reviewed and included on the basis of the quality of evidence and the authors' discretion. Conclusions KTS is characterized by a clinical triad of extremity varicosities, cutaneous vascular malformations, and hypertrophy of soft tissues and long bones. The diagnosis is clinically supplemented with magnetic resonance imaging and computed tomography. Although this syndrome is associated with significant comorbidities, such as pain, edema, ulcerations, and pruritus, it is rarely the cause of death. The backbone of treatment is nonoperative in nature but should be supplemented with minimally invasive, endovascular, and rarely open surgical procedures for refractory cases

Renal Autotransplant and Celiac Artery Bypass for Aneurysmal Degeneration Related to Neurofibromatosis Type 1

We present a case of an 18-year-old female with neurofibromatosis type 1 who presented with abdominal pain and weight loss secondary to chronic mesenteric ischemia due to celiac axis occlusion and was subsequently found to have multiple visceral artery aneurysms. Of clinical significance, 2 aneurysms of the right renal artery were noted at the hilum, with the larger one having a diameter of 2.4 cm. After initial endovascular treatment with stenting of a concurrent pancreaticoduodenal artery pseudoaneurysm, staged aorto-hepatic bypass and right nephrectomy with renal autotransplantation after back table resection of the aneurysmal segments were successfully completed

Treatment of a traumatic aortic bifurcation injury with an iliac branch endoprosthesis

We present the case of a 62-year-old man who sustained a traumatic distal aortic injury associated with an adjacent lumbar vertebral body fracture resulting from a 20-ft fall. Given the site of injury, an iliac artery branched endograft was deployed off-label to preserve the aortic bifurcation and cover a limited amount of healthy aorta to preserve the collaterals. The procedure was successful, with no intraoperative complications or evidence of an endoleak. The aortic bifurcation and distal iliac arteries remained widely patent by computed tomography angiography at the follow-up examination without evidence of sequelae

TSG-6 is highly expressed in human abdominal aortic aneurysms

BACKGROUND: The formation of abdominal aortic aneurysms (AAA) is characterized by a dominance of proinflammatory forces that result in smooth muscle cell apoptosis, extracellular matrix degradation, and progressive diameter expansion. Additional defects in the antiinflammatory response may also play a role but have yet to be fully characterized. TSG-6 (TNF-stimulated gene-6) is a potent antiinflammatory protein involved in extracellular matrix stabilization and cell migration active in many pathological conditions. Here, we describe its role in AAA formation. METHODS: Blood and/or aortic tissue samples were collected from organ donors, subjects undergoing elective AAA screening, and open surgical AAA repair. Aortic specimens collected were preserved for IHC or immediately assayed after tissue homogenization. Protein concentrations in tissue and plasma were assayed by ELISA. All immune cell populations were assayed using FACS. In vitro, macrophage polarization from monocytes was performed with young, healthy donor PBMCs. RESULTS: TSG-6 was found to be abnormally elevated in both the plasma and aortic wall of patients with AAA compared with healthy and risk-factor matched non-AAA donors. We observed the highest tissue concentration of TSG-6 in the less-diseased proximal and distal shoulders compared with the central aspect of the aneurysm. IHC localized most TSG-6 to the tunica media with minor expression in the tunica adventitia of the aortic wall. Higher concentrations of both M1 and M2 macrophages where also observed, however M1/M2 ratios were unchanged from healthy controls. We observed no difference in M1/M2 ratios in the peripheral blood of risk-factor matched non-AAA and AAA patients. Interesting, TSG-6 inhibited the polarization of the antiinflammatory M2 phenotype in vitro. CONCLUSIONS: AAA formation results from an imbalance of inflammatory forces causing aortic wall infiltration of mononuclear cells leading to the vessel breakdown. In the AAA condition, we report an elevation of TSG-6 expression in both the aortic wall and the peripheral circulation

Metformin does not reduce inflammation in diabetics with abdominal aortic aneurysm or at high risk of abdominal aortic aneurysm formation

Introduction The protective effect of diabetes mellitus on abdominal aortic aneurysm formation and growth has been repeatedly observed in population studies but continues to be poorly understood. However, recent investigations have suggested that metformin, a staple antihyperglycemic medication, may be independently protective against abdominal aortic aneurysm formation and growth. Therefore, we describe the effect of metformin in abdominal aortic aneurysm and at-risk patients on markers of inflammation, the driver of early abdominal aortic aneurysm formation and growth. Methods Peripheral blood was collected from patients previously diagnosed with abdominal aortic aneurysm or presenting for their U.S. Preventive Task Force-recommended abdominal aortic aneurysm screening. Plasma and circulating peripheral blood mononuclear cells were isolated using Ficoll density centrifugation. Circulating plasma inflammatory and regulatory cytokines were assessed with enzyme-linked immunosorbent assays. CD4+ cell phenotyping was performed using flow cytometric analysis and expressed as a proportion of total CD4+ cells. To determine the circulating antibody to self-antigen response, a modified enzyme-linked immunosorbent assay was performed against antibodies to collagen type V and elastin fragments. Results Peripheral blood was isolated from 266 patients without diabetes mellitus (n=182), with diabetes mellitus not treated with metformin (n=34), and with diabetes mellitus actively taking metformin (n=50) from 2015 to 2017. We found no differences in the expression of Tr1, Th17, and Treg CD4+ fractions within diabetics ± metformin. When comparing inflammatory cytokines, we detected no differences in IL-1β, IL-6, IL-17, IL-23, IFN-γ, and TNF-α. Conversely, no differences were observed pertaining to the expression to regulatory cytokines IL-4, IL-10, IL-13, TSG-6, or TGF-β. Lastly, no differences in expression of collagen type V and elastin fragment antigen and/or antibodies were detected with metformin use in diabetics. Conclusion Metformin in diabetics at-risk for abdominal aortic aneurysm or diagnosed with abdominal aortic aneurysm does not seem to alter the peripheral inflammatory environment