Mechanical aortic valve may no longer be a contraindication to inner branch aortic arch endografts.

OBJECTIVES: The presence of a mechanical aortic valve has been a contraindication to the use of an arch branch aortic endograft due to the risk of damaging the valve, resulting in acute aortic regurgitation, or a trapped endograft. METHODS: We present a 67-year-old woman, with a background of Marfan's syndrome and a previous Bentall's procedure, who presented with a symptomatic enlarging aortic arch and descending thoracic aortic aneurysm, with a type 1A endoleak. RESULTS: Using an inner branch arch endograft (Cook Medical, Bloomington, Indiana), the nose cone of the delivery system was passed laterally through the semi-circular aperture of the mechanical aortic valve to facilitate deployment just distal to the coronary buttons. CONCLUSIONS: With advancement of endovascular technology, techniques and experience, endovascular aortic arch repair in the presence of a mechanical aortic valve is feasible.

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, γ-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: γ-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 γ-H2AX or pATM expression after open repair. Leg protection abrogated γ-H2AX and pATM response after branched endovascular aortic repair/fenestrated endovascular aortic repair. The expression of γ-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.

Mycotic Aneurysm following a Dog Bite: The Value of the Clinical History and Molecular Diagnostics.

A 63-year-old Caucasian taxi driver presented with a 3-week history of malaise, night sweats, 7 kg weight loss, generalized arthralgia, and persistent mid-lower abdominal pain. Blood inflammatory markers were raised, and a computed tomography scan demonstrated an irregular degeneration of the infrarenal aorta, with a differential diagnosis including aortic infection. An urgent type IV thoracoabdominal aneurysm repair was performed with a rifampicin-soaked aortic tube graft during an open procedure. No organisms were grown from multiple peripheral blood cultures or culture of the affected aorta. However, subsequent 16S ribosomal polymerase chain reaction analysis of the resected aorta identified Capnocytophaga canimorsus as the causative organism-a commensal that lives in the mouth of dogs and cats. The patient subsequently gave a history of multiple bites from his pet dog over recent months-the likely source of infection. He was treated with 8 weeks of intravenous antibiotics before switching to oral antibiotics for an additional 6 weeks.

Antiangiogenic therapy inhibits venous thrombus resolution.

OBJECTIVE: Venous thromboembolism is a common complication in patients with cancer, resulting in significant morbidity and mortality. Clinical studies suggest that the incidence of venous thromboembolic events increased after treatment of these patients with antiangiogenic agents. Thrombi resolve through a process of remodeling, involving the formation of microvascular channels within the thrombus. Our aim was to determine whether inhibiting angiogenesis affects venous thrombus resolution. APPROACH AND RESULTS: Thrombus was induced in the inferior vena cava of mice. These mice were treated with axitinib (50 mg/kg per day), 2-methoxyestradiol (2ME, 150 mg/kg per day), or vehicle control. Thrombus size, recanalization, neovascularization, inflammatory cell content, and collagen content were assessed after axitinib (days 3, 10, 17) and 2ME (day 10 only) treatment (n=6/group). Axitinib treatment resulted in reduced thrombus resolution (P<0.002) and vein recanalization (P<0.001) compared with vehicle-treated controls. This was associated with inhibition of organization as seen through reduced thrombus neovascularization (P<0.0001) and collagen (P<0.0001) content, as well as reduced macrophage accumulation in the thrombus (P<0.001). Treatment with a second antiangiogenic agent, 2ME, mirrored these findings, with a similar order of magnitude of effect of treatment over vehicle control in all of the parameters measured, with the exception of neutrophil content, which was significantly reduced after 2ME treatment but not affected by axitinib. CONCLUSIONS: Antiangiogenic therapy (using axitinib and 2ME) inhibits the resolution of venous thrombi, which could lead to persistent venous obstruction and the possibility of thrombus extension. This potential prolongation of venous occlusion by antiangiogenic agents should therefore be taken into consideration in trials of these agents and when managing the complications of venous thromboembolic events in patients with cancer.

Magnetic resonance T1 relaxation time of venous thrombus is determined by iron processing and predicts susceptibility to lysis.

BACKGROUND: The magnetic resonance longitudinal relaxation time (T1) changes with thrombus age in humans. In this study, we investigate the possible mechanisms that give rise to the T1 signal in venous thrombi and whether changes in T1 relaxation time are informative of the susceptibility to lysis. METHODS AND RESULTS: Venous thrombosis was induced in the vena cava of BALB/C mice, and temporal changes in T1 relaxation time correlated with thrombus composition. The mean T1 relaxation time of thrombus was shortest at 7 days following thrombus induction and returned to that of blood as the thrombus resolved. T1 relaxation time was related to thrombus methemoglobin formation and further processing. Studies in inducible nitric oxide synthase (iNOS(-/-))-deficient mice revealed that inducible nitric oxide synthase mediates oxidation of erythrocyte lysis-derived iron to paramagnetic Fe3+, which causes thrombus T1 relaxation time shortening. Studies using chemokine receptor-2-deficient mice (Ccr2(-/-)) revealed that the return of the T1 signal to that of blood is regulated by removal of Fe3+ by macrophages that accumulate in the thrombus during its resolution. Quantification of T1 relaxation time was a good predictor of successful thrombolysis with a cutoff point of <747 ms having a sensitivity and specificity to predict successful lysis of 83% and 94%, respectively. CONCLUSIONS: The source of the T1 signal in the thrombus results from the oxidation of iron (released from the lysis of trapped erythrocytes in the thrombus) to its paramagnetic Fe3+ form. Quantification of T1 relaxation time appears to be a good predictor of the success of thrombolysis.

Extra-aortic mycotic aneurysm due to group A Streptococcus after pharyngitis.

Mycotic aneurysms, especially outside the aorta, are uncommon, with group A Streptococcus a particularly rare cause. We report a case of extra-aortic mycotic aneurysm following a sore throat without demonstrable bacteremia where identification of the pathological organism was made by molecular diagnostic techniques after a standard laboratory culture was negative.

Endovascular repair of the aorta and aortic arch arteries damaged during mediastinoscopy.

Despite advances in imaging techniques, mediastinoscopy remains an important tool for the staging of the mediastinum in non-small cell lung cancer and diagnosing lymphoma with mediastinal adenopathy. Injury to the arterial system during mediastinoscopy is infrequent but a potentially fatal complication. We report three cases of injury to the aorta and supra-aortic arteries sustained during mediastinoscopy. These were effectively managed by endovascular techniques. Patient recovery was uncomplicated and median length of stay was 3 days. This technique avoids major open surgery in a high-risk group of patients and may offer a mortality benefit and more rapid resumption of oncological treatment.

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.

Endovascular treatment of acute aortic syndrome.

BACKGROUND: The term acute aortic syndrome (AAS) encompasses a range of conditions that have a risk of imminent aortic rupture and where delays in treatment result in increased mortality. Endovascular treatment offers an attractive alternative to open surgery but little is known about the durability of the repair and the factors that predict mortality. METHODS: Prospective data were collected for a cohort of 110 consecutive patients with endovascular treatment for AAS. Patient and procedural characteristics were related to short- and midterm outcome using multivariate logistic regression analysis. RESULTS: There were 75 men and 35 women with a median age of 68 (range 57-76) years. The pathologies treated were acute dissection (35), symptomatic aneurysm (32), infected aneurysm (18), transection (12), chronic dissection (9), penetrating ulcer (3), and intramural hematoma (1). Thirty-day mortality was 12.7% and this was associated with hypotension (odds ratio [OR], 5.25), use of general anesthetic (OR, 5.23), long procedure duration (OR, 2.03), and increasing age (OR, 1.07). The causes of death were aortic rupture (4), myocardial infarction (4), stroke (3), and multisystem organ failure (3). The stroke and paraplegia rates were 7.3% and 6.4%, respectively. The 1-year survival was 81% and the 5-year survival 63%. Secondary procedures were required in 13 (11.8%) patients. Factors associated with death at 1 year were presence of an aortic fistula (OR, 9.78), perioperative stroke (OR, 5.87), and use of general anesthetic (OR, 3.76); and at 5 years were aortic fistula (OR, 12.31) and increasing age (OR, 1.06). CONCLUSIONS: Acute aortic syndrome carries significant early and late mortality. Emergency endovascular repair offers a minimally invasive treatment option associated with acceptable short and midterm results. Continued surveillance is important as secondary procedures and aortic-related deaths continue to occur throughout the follow-up period.

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.

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

OBJECTIVES: This study aimed to determine the role played by academic foundation programmes in influencing junior doctors' desire to pursue a career in academic medicine. METHODS: We conducted an online questionnaire-based study of doctors who were enrolled on or had completed academic foundation programmes in the UK. There were 92 respondents (44 men, 48 women). Of these, 32 (35%) possessed a higher degree and 73 (79%) had undertaken a 4-month academic placement during Foundation Year 2. Outcomes were measured using Likert scale-based ordinal response data. RESULTS: From a cohort of 115 academic foundation trainees directly contacted, 46 replies were obtained (40% response rate). A further 46 responses were obtained via indirect notification through local programme directors. From the combined responses, the majority (77%) wished to pursue a career in academia at the end of the academic Foundation Year (acFY) programme. Feeling well informed about academic careers (odds ratio [OR] 16.9, p=0.005) and possessing a higher degree (OR 31.1, p=0.013) were independently associated with an increased desire to continue in academia. Concern about reduced clinical experience whilst in academic training dissuaded from continuing in academia (OR 0.15, p=0.026). Many respondents expressed concerns about autonomy, the organisation of the programme and the quantity and quality of academic teaching received. However, choice of work carried out during the academic block was the only variable independently associated with increasing the desire of respondents to pursue a career in academia following their experiences in the acFY programme (OR 6.3, p=0.007). CONCLUSIONS: The results support the provision of well-organised academic training programmes that assist junior clinical academics in achieving clinical competencies whilst providing protected academic time, information about further academic training pathways and autonomy in their choice of academic work.