Melissa Suh

Elastin-Derived Peptides Promote Abdominal Aortic Aneurysm Formation by Modulating M1/M2 Macrophage Polarization

Abdominal aortic aneurysm is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix degradation. Damage to elastin in the extracellular matrix results in release of elastin-derived peptides (EDPs), which are chemotactic for inflammatory cells such as monocytes. Their effect on macrophage polarization is less well known. Proinflammatory M1 macrophages initially are recruited to sites of injury, but, if their effects are prolonged, they can lead to chronic inflammation that prevents normal tissue repair. Conversely, anti-inflammatory M2 macrophages reduce inflammation and aid in wound healing. Thus, a proper M1/M2 ratio is vital for tissue homeostasis. Abdominal aortic aneurysm tissue reveals a high M1/M2 ratio in which proinflammatory cells and their associated markers dominate. In the current study, in vitro treatment of bone marrow–derived macrophages with EDPs induced M1 macrophage polarization. By using C57BL/6 mice, Ab-mediated neutralization of EDPs reduced aortic dilation, matrix metalloproteinase activity, and proinflammatory cytokine expression at early and late time points after aneurysm induction. Furthermore, direct manipulation of the M1/M2 balance altered aortic dilation. Injection of M2-polarized macrophages reduced aortic dilation after aneurysm induction. EDPs promoted a proinflammatory environment in aortic tissue by inducing M1 polarization, and neutralization of EDPs attenuated aortic dilation. The M1/M2 imbalance is vital to aneurysm formation.

Recurrent Admissions for Respiratory Distress Caused by Large Renal AVF.

Renal arteriovenous fistulas (AVFs) are an uncommon complication of nephrectomy. In this report, we present the case of a 66-year-old female presenting with progressive dyspnea on exertion and exercise intolerance. She was diagnosed and treated for adult onset reactive airway disease. The patient underwent nephrectomy at age 18 secondary to recurrent pyelonephritis from vesicoureteral reflux. She underwent a surveillance computed tomography (CT) scan to evaluate a small ascending aneurysm that was initially detected on cardiac echocardiogram. A large left renal AVF was detected incidentally on the CT scan. The fistula was successfully treated by ligation of the renal artery with resolution of pulmonary symptoms.

IL-1β (Interleukin-1β) and TNF-α (Tumor Necrosis Factor-α) Impact Abdominal Aortic Aneurysm Formation by Differential Effects on Macrophage Polarization

Objective— Abdominal aortic aneurysms are inflammatory in nature and are associated with some risk factors that also lead to atherosclerotic occlusive disease, most notably smoking. The purpose of our study was to identify differential cytokine expression in patients with abdominal aortic aneurysm and those with atherosclerotic occlusive disease. Based on this analysis, we further explored and compared the mechanism of action of IL (interleukin)-1&bgr; versus TNF-&agr; (tumor necrosis factor-&agr;) in abdominal aortic aneurysm formation. Approach and Results— IL-1&bgr; was differentially expressed in human plasma with lower levels detected in patients with abdominal aortic aneurysm compared with matched atherosclerotic controls. We further explored its mechanism of action using a murine model and cell culture. Genetic deletion of IL-1&bgr; and IL-1R did not inhibit aneurysm formation or decrease MMP (matrix metalloproteinase) expression. The effects of IL-1&bgr; deletion on M1 macrophage polarization were compared with another proinflammatory cytokine, TNF-&agr;. Bone marrow-derived macrophages from IL-1&bgr;−/− and TNF-&agr;−/− mice were polarized to an M1 phenotype. TNF-&agr; deletion, but not IL-1&bgr; deletion, inhibited M1 macrophage polarization. Infusion of M1 polarized TNF-&agr;−/− macrophages inhibited aortic diameter growth; no inhibitory effect was seen in mice infused with M1 polarized IL-1&bgr;−/− macrophages. Conclusions— Although IL-1&bgr; is a proinflammatory cytokine, its effects on aneurysm formation and macrophage polarization differ from TNF-&agr;. The differential effects of IL-1&bgr; and TNF-&agr; inhibition are related to M1/M2 macrophage polarization and this may account for the differences in clinical efficacy of IL-1&bgr; and TNF-&agr; antibody therapies in management of inflammatory diseases.

Transesophageal Echocardiogram-Guided Stent Placement in Superior Vena Cava Syndrome Secondary to Granulomatous Lung Disease: A Case Series and Literature Review

Obstruction of the superior vena cava (SVC) is an uncommon, but potentially life-threatening condition due to likely development of edema in the head and neck and potential respiratory compromise. Less than half of those affected by SVC syndrome survive more than a year. Obstruction can be from neoplasms or secondary to benign disease. Treatment for most cases of symptomatic SVC syndrome involves placement of a stent to relieve the stenosis. Serious complications such as stent migration, pulmonary embolism, and cardiac tamponade can occur in 5% to 10% of cases, and inadequate imaging of the SVC–atrial junction by fluoroscopy contributes to these problems. The overlapping contrast in the atrium makes it difficult to precisely place the distal end of the stent, potentially allowing for embolization of the stent to occur. We present a case series of 3 patients wherein transesophageal echocardiography was used for guidance of stent placement in the SVC and significantly aided in placement.

Model for prioritization of Graduate Medical Education funding at a university setting - Engagement of GME committee with the Clinical Enterprise

BACKGROUND Funding for graduate medical education (GME) is becoming scarce and is likely to worsen. There is a higher degree of accountability and return on investment demanded from public funds dedicated to GME. Academic centers (AC) partnered with clinical enterprises (CE) are finding it increasingly difficult to retain sustainable funding streams for GME activities. METHODS To develop and implement a novel algorithmic funding model at one AC in symbiotic partnership with the CE for all 50 GME programs with nearly 500 residents. RESULTS A new GME Finance and Workforce Committee was convened which was tasked with developing the novel algorithmic financial model to prioritize GME funding. Early outcomes measures that were monitored consisted of: satisfaction of all stakeholders and financial savings. CONCLUSIONS The model was presented to all the stakeholders and was well received and approved. Early signs, demonstrated AC and CE satisfaction with the model, financial savings and increased efficiency. This GME funding model may serve as a template for other academic centers with tailored modifications to suit their local needs, demands and constraints.