Oliver Lyons

Genes regulating lymphangiogenesis control venous valve formation and maintenance in mice

Chronic venous disease and venous hypertension are common consequences of valve insufficiency, yet the molecular mechanisms regulating the formation and maintenance of venous valves have not been studied. Here, we provide what we believe to be the first description of venous valve morphogenesis and identify signaling pathways required for the process. The initial stages of valve development were found to involve induction of ephrin-B2, a key marker of arterial identity, by venous endothelial cells. Intriguingly, developing and mature venous valves also expressed a repertoire of proteins, including prospero-related homeobox 1 (Prox1), Vegfr3, and integrin-α9, previously characterized as specific and critical regulators of lymphangiogenesis. Using global and venous valve-selective knockout mice, we further demonstrate the requirement of ephrin-B2 and integrin-α9 signaling for the development and maintenance of venous valves. Our findings therefore identified molecular regulators of venous valve development and maintenance and highlighted the involvement of common morphogenetic processes and signaling pathways in controlling valve formation in veins and lymphatic vessels. Unexpectedly, we found that venous valve endothelial cells closely resemble lymphatic (valve) endothelia at the molecular level, suggesting plasticity in the ability of a terminally differentiated endothelial cell to take on a different phenotypic identity.

Leukocytes and the natural history of deep vein thrombosis: current concepts and future directions

Observational studies have shown that inflammatory cells accumulate within the thrombus and surrounding vein wall during the natural history of venous thrombosis. More recent studies have begun to unravel the mechanisms that regulate this interaction and have confirmed that thrombosis and inflammation are intimately linked. This review outlines our current knowledge of the complex relationship between inflammatory cell activity and venous thrombosis and highlights new areas of research in this field. A better understanding of this relationship could lead to the development of novel therapeutic targets that inhibit thrombus formation or promote its resolution.

Is endovascular repair of mycotic aortic aneurysms a durable treatment option

OBJECTIVE Endovascular repair for degenerative aortic aneurysms is well established, but its role in those with infective pathology remains controversial. This study aims to assess the durability of endovascular repair with a review of our midterm results. METHOD A retrospective analysis of a prospectively maintained endovascular database (1998-2008) was conducted, which identified 673 consecutive patients with aortic aneurysms. RESULTS Nineteen patients (2.8%) were identified with infected aortic aneurysms, in which there were a total of 23 separate aneurysms (16 thoracic and seven abdominal). Six patients (32%) presented with rupture. Eleven patients (58%) had received antibiotics preoperatively for a median duration of 11 days (1-54 days). Fifteen of the 19 (79%) had positive blood cultures, with Staphylococcus aureus being the most common organism. All 19 patients underwent endovascular repair. There were three Type I endoleaks (one requiring conversion to open repair) and two Type II endoleaks. One patient developed transient paraplegia, resolved by cerebrovascular fluid (CSF) drainage, and one patient had a stroke. The 30-day mortality was 11%, and survival at median follow-up of 20 months (0-83 months) was 73%. All eight deaths in the series were related to aneurysm. CONCLUSION Endovascular treatment of infective aortic pathology provides an early survival benefit; however, concerns over on-going graft infection remain.

Endovascular Treatment of Mycotic Aortic Aneurysms A European Multicenter Study

Background— Mycotic aortic aneurysm (MAA) is a rare and life-threatening disease. The aim of this European multicenter collaboration was to study the durability of endovascular aortic repair (EVAR) of MAA, by assessing late infection–related complications and long-term survival. Methods and Results— All EVAR treated MAAs, between 1999 and 2013 at 16 European centers, were retrospectively reviewed. One hundred twenty-three patients with 130 MAAs were identified. Mean age was 69 years (range 39–86), 87 (71%) were men, 58 (47%) had immunodeficiency, and 47 (38%) presented with rupture. Anatomic locations were ascending/arch (n=4), descending (n=34), paravisceral (n=15), infrarenal aorta (n=63), and multiple (n=7). Treatments were thoracic EVAR (n=43), fenestrated/branched EVAR (n=9), and infrarenal EVAR (n=71). Antibiotic was administered for mean 30 weeks. Mean follow-up was 35 months (range 1 week to 149 months). Six patients (5%) were converted to open repair during follow-up. Survival was 91% (95% confidence interval, 86% to 96%), 75% (67% to 83%), 55% (44% to 66%), and 41% (28% to 54%) after 1, 12, 60, and 120 months, respectively. Infection-related death occurred in 23 patients (19%), 9 after discontinuation of antibiotic treatment. A Cox regression analysis demonstrated non-Salmonella–positive culture as predictors for late infection–related death. Conclusions— Endovascular treatment of MAA is feasible and for most patients a durable treatment option. Late infections do occur, are often lethal, and warrant long-term antibiotic treatment and follow-up. Patients with non-Salmonella–positive blood cultures were more likely to die from late infection. # CLINICAL PERSPECTIVE {#article-title-32}Background— Mycotic aortic aneurysm (MAA) is a rare and life-threatening disease. The aim of this European multicenter collaboration was to study the durability of endovascular aortic repair (EVAR) of MAA, by assessing late infection–related complications and long-term survival. Methods and Results— All EVAR treated MAAs, between 1999 and 2013 at 16 European centers, were retrospectively reviewed. One hundred twenty-three patients with 130 MAAs were identified. Mean age was 69 years (range 39–86), 87 (71%) were men, 58 (47%) had immunodeficiency, and 47 (38%) presented with rupture. Anatomic locations were ascending/arch (n=4), descending (n=34), paravisceral (n=15), infrarenal aorta (n=63), and multiple (n=7). Treatments were thoracic EVAR (n=43), fenestrated/branched EVAR (n=9), and infrarenal EVAR (n=71). Antibiotic was administered for mean 30 weeks. Mean follow-up was 35 months (range 1 week to 149 months). Six patients (5%) were converted to open repair during follow-up. Survival was 91% (95% confidence interval, 86% to 96%), 75% (67% to 83%), 55% (44% to 66%), and 41% (28% to 54%) after 1, 12, 60, and 120 months, respectively. Infection-related death occurred in 23 patients (19%), 9 after discontinuation of antibiotic treatment. A Cox regression analysis demonstrated non-Salmonella–positive culture as predictors for late infection–related death. Conclusions— Endovascular treatment of MAA is feasible and for most patients a durable treatment option. Late infections do occur, are often lethal, and warrant long-term antibiotic treatment and follow-up. Patients with non-Salmonella–positive blood cultures were more likely to die from late infection.

Occupational Radiation Exposure During Endovascular Aortic Procedures

OBJECTIVES To measure the radiation exposure of the operating team during endovascular aortic procedures, and to determine factors that predict high exposures. MATERIALS AND METHODS Electronic dosimeters placed over and under protective lead garments, were used to prospectively record radiation exposure during endovascular aortic repairs performed in a designated interventional radiology suite. Univariate and multivariate linear regression analyses of predictors of radiation exposure were performed. RESULTS A total of 26 infra-renal and 10 thoracic endovascular cases were studied. Median (IQR) patient age and body mass index were 76.0 (70.0-81.8) years and 26.2 (23.9-28.9) kg/m(2) respectively. Over-lead exposure to the operator was higher for thoracic than for infra-renal procedures (421.0 [233.8-597.8] μSv vs. 52.5 [27.8-179.8] μSv, p = .0003), reflecting a significant exposure to unprotected parts of the body. Under-lead exposures for operator and assistant were 5.5 (2.0-14.2) μSv and 1.0 (0.0-2.3) μSv respectively, which for an average caseload would comply with total body effective dose limits. Type of case and percentage of digital subtraction angiography (DSA) time in left anterior oblique angulations predicted dose to the operator (p < .0001). CONCLUSIONS Thoracic procedures, DSA runs and obliquity of the C-arm are strong predictors of radiation exposure during endovascular aortic repairs. Understanding scatter radiation dynamics and instigating measures to minimise radiation exposure should be mandatory.

Successful Endovascular Repair of Acute Type B Aortic Dissection in Undiagnosed Ehlers-Danlos Syndrome Type IV

A 61-year-old man presented with an acute type B aortic dissection for which a stent-graft was introduced. He remains complication-free 4 years onwards and has since been diagnosed with Ehlers-Danlos syndrome type IV (EDS IV). His particular mutation is predicted to result in lesser levels of normal collagen and may explain his favourable outcome from endovascular intervention. Understanding the genotype-phenotype correlation may influence the choice of therapy offered to patients with EDS IV.

Impact of UK academic foundation programmes on aspirations to pursue a career in academia

Medical Education 2010: 44: 996–1005

Endovascular repair of a tuberculous mycotic thoracic aortic aneurysm with a custom-made device

Mycotic aortic aneurysms are rare and it is unlikely that any center will obtain extensive experience in their management. The aim of treatment is to repair the aorta and eradicate the infection with minimal operative and postoperative risk. We describe a case in which a custom-made endovascular stent graft provided the optimal treatment strategy and remained durable at 4 years of follow-up.

Radiation-Induced DNA Damage in Operators Performing Endovascular Aortic Repair

Background: Radiation exposure during fluoroscopically guided interventions such as endovascular aortic repair (EVAR) is a growing concern for operators. This study aimed to measure DNA damage/repair markers in operators perfoming EVAR. Methods: Expression of the DNA damage/repair marker, &ggr;-H2AX and DNA damage response marker, phosphorylated ataxia telangiectasia mutated (pATM), were quantified in circulating lymphocytes in operators during the peri-operative period of endovascular (infrarenal, branched, and fenestrated) and open aortic repair using flow cytometry. These markers were separately measured in the same operators but this time wearing leg lead shielding in addition to upper body protection and compared with those operating with unprotected legs. Susceptibility to radiation damage was determined by irradiating operators’ blood in vitro. Results: &ggr;-H2AX and pATM levels increased significantly in operators immediately after branched endovascular aortic repair/fenestrated endovascular aortic repair (P<0.0003 for both). Only pATM levels increased after infrarenal endovascular aortic repair (P<0.04). Expression of both markers fell to baseline in operators after 24 hours (P<0.003 for both). There was no change in &ggr;-H2AX or pATM expression after open repair. Leg protection abrogated &ggr;-H2AX and pATM response after branched endovascular aortic repair/fenestrated endovascular aortic repair. The expression of &ggr;-H2AX varied significantly when operators’ blood was exposed to the same radiation dose in vitro (P<0.0001). Conclusions: This is the first study to detect an acute DNA damage response in operators performing fluoroscopically guided aortic procedures and highlights the protective effect of leg shielding. Defining the relationship between this response and cancer risk may better inform safe levels of chronic low-dose radiation exposure.

Endovascular management of Stanford type a dissection or intramural hematoma with a distal primary entry tear.

A systematic review was conducted of all published cases of endovascular repair of retrograde Stanford type A dissection or intramural hematoma to determine mortality of this less invasive approach to treatment. Using the PRISMA guidelines, databases were searched for any of the terms ‘dissect