Inhibition of prolyl hydroxylase domain proteins selectively enhances venous thrombus neovascularisation.

BACKGROUND: Hypoxia within acute venous thrombi is thought to drive resolution through stabilisation of hypoxia inducible factor 1 alpha (HIF1α). Prolyl hydroxylase domain (PHD) isoforms are critical regulators of HIF1α stability. Non-selective inhibition of PHD isoforms with l-mimosine has been shown to increase HIF1α stabilisation and promote thrombus resolution. OBJECTIVE: The aim of this study was to investigate the therapeutic potential of PHD inhibition in venous thrombus resolution. METHODS: Thrombosis was induced in the inferior vena cava of mice using a combination of flow restriction and endothelial activation. Gene and protein expression of PHD isoforms in the resolving thrombus was measured by RT-PCR and immunohistochemistry. Thrombus resolution was quantified in mice treated with pan PHD inhibitors AKB-4924 and JNJ-42041935 or inducible all-cell Phd2 knockouts by micro-computed tomography, 3D high frequency ultrasound or endpoint histology. RESULTS: Resolving venous thrombi demonstrated significant temporal gene expression profiles for PHD2 and PHD3 (P < 0.05), but not for PHD1. PHD isoform protein expression was localised to early and late inflammatory cell infiltrates. Treatment with selective pan PHD inhibitors, AKB-4924 and JNJ-42041935, enhanced thrombus neovascularisation (P < 0.05), but had no significant effect on overall thrombus resolution. Thrombus resolution or its markers, macrophage accumulation and neovascularisation, did not differ significantly in inducible all-cell homozygous Phd2 knockouts compared with littermate controls (P > 0.05). CONCLUSIONS: This data suggests that PHD-mediated thrombus neovascularisation has a limited role in the resolution of venous thrombi. Directly targeting angiogenesis alone may not be a viable therapeutic strategy to enhance venous thrombus resolution.

Diagnosis of Aortic Graft Infection: A Case Definition by the Management of Aortic Graft Infection Collaboration (MAGIC).

OBJECTIVE/BACKGROUND: The management of aortic graft infection (AGI) is highly complex and in the absence of a universally accepted case definition and evidence-based guidelines, clinical approaches and outcomes vary widely. The objective was to define precise criteria for diagnosing AGI. METHODS: A process of expert review and consensus, involving formal collaboration between vascular surgeons, infection specialists, and radiologists from several English National Health Service hospital Trusts with large vascular services (Management of Aortic Graft Infection Collaboration [MAGIC]), produced the definition. RESULTS: Diagnostic criteria from three categories were classified as major or minor. It is proposed that AGI should be suspected if a single major criterion or two or more minor criteria from different categories are present. AGI is diagnosed if there is one major plus any criterion (major or minor) from another category. (i) Clinical/surgical major criteria comprise intraoperative identification of pus around a graft and situations where direct communication between the prosthesis and a nonsterile site exists, including fistulae, exposed grafts in open wounds, and deployment of an endovascular stent-graft into an infected field (e.g., mycotic aneurysm); minor criteria are localized AGI features or fever ≥38°C, where AGI is the most likely cause. (ii) Radiological major criteria comprise increasing perigraft gas volume on serial computed tomography (CT) imaging or perigraft gas or fluid (≥7 weeks and ≥3 months, respectively) postimplantation; minor criteria include other CT features or evidence from alternative imaging techniques. (iii) Laboratory major criteria comprise isolation of microorganisms from percutaneous aspirates of perigraft fluid, explanted grafts, and other intraoperative specimens; minor criteria are positive blood cultures or elevated inflammatory indices with no alternative source. CONCLUSION: This AGI definition potentially offers a practical and consistent diagnostic standard, essential for comparing clinical management strategies, trial design, and developing evidence-based guidelines. It requires validation that is planned in a multicenter, clinical service database supported by the Vascular Society of Great Britain & Ireland.

18F-FDG PET-CT uptake is a feature of both normal diameter and aneurysmal aortic wall and is not related to aneurysm size.

PURPOSE: Aortic metabolic activity is suggested to correlate with presence and progression of aneurysmal disease, but has been inadequately studied. This study investigates the 2-[(18)F] fluoro-2-deoxy-D-glucose ((18)F-FDG) uptake in a population of infra-renal abdominal aortic aneurysms (AAA), compared to a matched non-aneurysmal control group. METHODS: The Positron Emission Tomography - Computed Tomography (PET/CT) database was searched for infra-renal AAA. Exclusion criteria were prior repair, vasculitis, and saccular/mycotic thoracic or thoraco-abdominal aneurysms. Matching of 159 non-aneurysmal (<3 cm diameter) controls from the same population was assessed. Infra-renal aortic wall FDG uptake was assessed using visual analysis; maximum standardized uptake value (SUVmax) and target to background mediastinal blood pool ratio (TBR) were documented. Predictors of FDG uptake (age, sex, aortic diameter, hypertension, statin use, and diabetes) were assessed using univariate analysis. Follow-up questionnaires were sent to referring clinicians. RESULTS: Aneurysms (n = 151) and controls (n = 159) were matched (p > 0.05) for age, sex, diabetes, hypertension, smoking status, statin use, and indication for PET/CT. Median aneurysm diameter was 5.0 cm (range 3.2-10.4). On visual analysis there was no significant difference in the overall numbers with increased visual uptake 24% (36/151) in the aneurysm group vs. 19% (30/159) in the controls, p = ns. SUVmax was slightly lower in the aneurysm group vs. controls (mean (2 SD) 1.75(0.79) vs. 1.84(0.58), p = 0.02). However there was no difference in TBR between the AAA group and controls (mean (2 SD) 1.03 (0.46) vs. 1.05(0.31), p = 0.36). During a median 18 (interquartile range 8-35) months' follow-up 20 were repaired and four were confirmed ruptured. CONCLUSIONS: The level of metabolic activity as assessed by (18)F-FDG PET/CT in infra-renal AAA does not correlate with aortic size and does not differ between aneurysms and matched controls.

Pathology specific early outcome after thoracic endovascular aortic repair.

OBJECTIVES: Endovascular intervention is established for treatment of thoracic aortic dissection and aneurysm. The aim of this study was to compare the incidence of all-cause and aortic-related in-hospital mortality, stroke, spinal cord ischaemia, and major adverse event rate for patients undergoing thoracic aortic endovascular intervention to see if there is a pathology-specific effect. METHODS: Data were collected prospectively and analysed retrospectively for a cohort of 309 consecutive patients with either thoracic aortic dissection or aneurysm over a 14-year period. RESULTS: There were 209 men and 100 women with a median age of 72 years (interquartile range [IQR] 63-78 years). Aneurysm affected 62% (193/309) of patients and 37% (116/309) had complicated type B aortic dissection, of whom 43% (50/116) had acute and 57% (66/116) chronic presentations. In patients with aortic dissection compared to aneurysm, there was no significant difference in all-cause in-hospital mortality (6.9% vs. 8.3% respectively, p = 0.827, relative risk [RR] 0.83, 95% confidence interval [CI] 0.37-1.88), stroke (6.0% vs 6.2%, p = 1.00, RR 0.971, CI 0.39-2.39), spinal cord ischaemia (6.0% vs 6.2%, p = 1.00, RR 1.030, CI 0.42-2.54), or major adverse event rate (16.4% vs. 16.6%, p = 1.00, RR 0.988, CI 0.59-1.66). The rate of aortic related death was four times greater in the dissection than in the aneurysm group (4/8 = 50% vs 2/16 = 12.5%, p = 0.06, RR 6.99, CI 0.92-52.5) although this did not reach statistical significance. CONCLUSIONS: There was no difference in the incidence of in-hospital mortality, stroke, and spinal cord ischaemia between aneurysm and dissection. The higher rate of aortic related death in the dissection group may indicate the need to refine the clinical management of these patients, including procedural planning, endograft design, and operative technique.

A grossly abnormal trachea- severe tracheal diverticulosis and Mounier-Kuhn syndrome.

A 53-year-old smoker presented with a history of recurrent lower respiratory tract infections. A diagnosis of Tracheal Diverticulosis due to Tracheobronchomegaly (Mounier-Kuhn Syndrome) was made. The clinical history, diagnosis and treatment options are discussed.

Venous thromboembolism prophylaxis in acute medical admissions to a university teaching hospital.

The objective of this study was to assess appropriate thromboprophylaxis prescription rates in a university hospital and to re-audit after a series of interventions. The notes of all acute medical patient admissions over a 4-week period were assessed for VTE risk factors and prescription of thromboprophylaxis. Subsequently, a series of hospital wide interventions including educational initiatives and a new drug prescription chart were introduced. 2 years post intervention the audit was repeated. Pre-intervention, 104 of 265 (39%) "at risk" patients were prescribed appropriate thromboprophylaxis. Post intervention the prescription rate increased to 108 of 188 (57%) "at risk patients". The results of the pre- intervention audit are consistent with the published literature. While there was a significant increase in prescription rates post intervention, over 40% of "at risk" patients still did not receive thromboprophylaxis highlighting the challenge in attempting to close the gap between guidelines and actual practice.

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.

A 14-year experience with aortic endograft infection: management and results.

OBJECTIVES: The management of thoracic and abdominal aortic endograft infection is complex and associated with high mortality. Cases are rare: a recent systematic review identified 117 reported cases; the largest reported series comprises 12 infected endografts. METHODS: We report 22 consecutive patients with infected abdominal or thoracic aortic endovascular devices implanted from 1998 to 2012. Management included extension with new devices, aneurysm sac drainage of pus/irrigation with antibiotics, endograft explantation, and axillo-(bi)femoral reconstruction. RESULTS: Twenty-two patients (16 men) were identified. Median age was 71 years (range, 43-88 years). Index devices were infra-renal endovascular repair (n = 13), and thoracic endovascular repair (n = 9) all for aneurysmal or pseudoaneurysmal disease. Seven (32%) had prior aortic surgery. Follow-up was complete in all cases; in survivors follow-up was a median of 29 (range, 12-45) months. The mortality from explantation of ten infra-renal devices was 1/10 (10%) on-table and a further 2/10 (20%) within 30 days. Device retention led to disease progression and death in all patients with infected endografts. Sac drainage/irrigation provided only temporary control of sepsis. Device extension can treat rupture, but additional devices became infected. CONCLUSION: Abdominal endograft explantation is high risk but may be curative. Appropriate selection of patients for infected endograft explantation remains a major challenge.

Predictors of outcome after endovascular repair for chronic type B dissection.

OBJECTIVES: To assess the durability of endovascular repair (TEVAR) in chronic type B dissection (CD) and identify factors predictive of outcome. DESIGN: Retrospective analysis of a prospective database. MATERIALS: Patients undergoing TEVAR for CD at a tertiary referral centre 2000-2010. METHODS: Analysis of pre-operative characteristics, operative outcome, false lumen thrombosis, aortic diameter and survival. RESULTS: 58 consecutive patients were included (49 elective, 9 urgent, mean age 66 years). Mean aortic diameter was 6.4 cm (Standard deviation SD 1.3 cm). Three patients died perioperatively (5%, 1 urgent, 2 elective). Complications included retrograde type A dissection (n = 3), paraplegia (1), and transient ischaemic attack (1). Estimated survival (Kaplan-Meier) was 89% (1-year) and 64% (3-years). Forty-seven patients had mid-term imaging follow-up at mean 38 months. Reintervention rate was 15% at 1-year and 29% at 3-years. Aortic diameter decreased in 24, was stable in 15 and increased in 8. Mid-term survival was higher in patients with aortic remodelling (reduction of aortic diameter >0.5 cm; 3-year 89%) than without (54%; Log Rank p = 0.005). Remodelling occurred with extensive false lumen thrombosis. CONCLUSION: Satisfactory mid-term outcome after TEVAR for CD remains a challenge. Survival is associated with aortic remodelling, which is related to persistence of flow in the false lumen.

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.

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.

Ruptured thoracoabdominal aortic aneurysm in a renal transplant patient with Alport's syndrome.

Alport's syndrome is a rare genetic disorder of type IV basement membrane collagen synthesis that typically presents with nephropathy, deafness, and ocular abnormalities. To the best of our knowledge, this is the first report in the world's literature of ruptured thoracoabdominal aortic aneurysm in a young patient with Alport's syndrome and a renal transplant. Hypotheses on an association between collagen disease in Alport's syndrome and aortic aneurysms are discussed.

Use of the double pigtail stent in stone retrieval following unsuccessful ureteroscopy.

Insertion of a double pigtail stent is known to cause ureteric dilatation. We analysed the effect of an indwelling double pigtail stent on the success rate of calculus extraction by second ureteroscopy when the initial ureteroscopy fails. Over a 12-month period, a first ureteroscopy failed in 42 patients; 30 were then treated by ureteroscopy combined with a ureteric stent and 12 were treated without a ureteric stent. The group with an indwelling stent had a successful second ureteroscopy or spontaneously passed the calculus in 24 cases (84%) compared with 5 unstented cases (45%). Ureterolithotomy was necessary in 2 patients with a stent and 3 with no stent. It was concluded that following failed ureteroscopic manipulation of calculi, insertion of a double pigtail stent was associated with a higher subsequent success rate for removal of stone by ureteroscopy and a consequent lower rate of ureterolithotomy.