Low Intensity Shockwave Treatment Modulates Macrophage Functions Beneficial to Healing Chronic Wounds.

Extracorporeal Shock Wave Therapy (ESWT) is used clinically in various disorders including chronic wounds for its pro-angiogenic, proliferative, and anti-inflammatory effects. However, the underlying cellular and molecular mechanisms driving therapeutic effects are not well characterized. Macrophages play a key role in all aspects of healing and their dysfunction results in failure to resolve chronic wounds. We investigated the role of ESWT on macrophage activity in chronic wound punch biopsies from patients with non-healing venous ulcers prior to, and two weeks post-ESWT, and in macrophage cultures treated with clinical shockwave intensities (150-500 impulses, 5 Hz, 0.1 mJ/mm2). Using wound area measurements and histological/immunohistochemical analysis of wound biopsies, we show ESWT enhanced healing of chronic ulcers associated with improved wound angiogenesis (CD31 staining), significantly decreased CD68-positive macrophages per biopsy area and generally increased macrophage activation. Shockwave treatment of macrophages in culture significantly boosted uptake of apoptotic cells, healing-associated cytokine and growth factor gene expressions and modulated macrophage morphology suggestive of macrophage activation, all of which contribute to wound resolution. Macrophage ERK activity was enhanced, suggesting one mechanotransduction pathway driving events. Collectively, these in vitro and in vivo findings reveal shockwaves as important regulators of macrophage functions linked with wound healing. This immunomodulation represents an underappreciated role of clinically applied shockwaves, which could be exploited for other macrophage-mediated disorders.

Excluder Stent Graft-Related Outcomes in Patients with Aortic Neck Anatomy Outside of Instructions For Use (IFU) within the Global Registry for Endovascular Aortic Treatment (GREAT): Mid-term Follow-Up Results.

BACKGROUND: The utilisation rate of endovascular aortic aneurysm repair has increased continuously over the past 2 decades. Endovascular aortic aneurysm repair is still performed frequently in patients with an unfavourable proximal seal zone, despite the associated late complications. PURPOSE: We aimed to evaluate the mid-term durability of the GORE® EXCLUDER® AAA Endoprosthesis, featuring the C3 delivery system, in patients with a proximal neck anatomy outside the instructions for use (IFU). METHODS: A retrospective sub-analysis of the Global Registry for Endovascular Aortic Treatment including patients treated for abdominal aortic aneurysms with the GORE EXCLUDER AAA Endoprosthesis (W.L. Gore & Associates, Inc, Flagstaff, Arizona) was performed. A "challenging neck" was defined as those treated outside the IFU with an aortic neck length <15 mm and/or aortic neck angle >60°. Cox proportional analyses were used to test for time-to-event differences between those treated within and outside the IFU while accounting for covariates, specifically proximal neck length and neck angle. The main outcomes assessed were 5-year all-cause mortality, 5-year endoleak development (type I or III), and 5-year device-related reinterventions. FINDINGS: Of the 3,324 patients included in the analysis, 411 (12.4%) had a challenging neck and 2,913 (87.6%) did not. The patients in the challenging neck group were significantly older (74.9 years vs. 73.2 years, p≤0.0001) and had a significantly larger aortic aneurysm diameter at the time of the intervention than those treated within the IFU (61.2 mm vs. 56.4 mm, P< 0.0001), shorter proximal neck length (18 mm vs. 30 mm, P< 0.0001) and larger infrarenal neck angle (60.8° vs. 25.8°, P< 0.0001). In the multivariate analysis, brachial access site and challenging neck were not independent risk factors; increased age was associated with a shorter time to mortality (hazard ratio 1.051, 95% confidence interval 1.039-1.062, P< 0.0001), as was the use of tobacco (hazard ratio 1.329, 95% confidence interval 1.124-1.571, P= 0.0009). The 5-year all-cause mortality (36.2% vs. 27.5%, P= 0.002) and aorta-related mortality (3.8% vs. 1.1%, P= 0.002) were significantly higher in the challenging neck group. The risk of death within 5 years also increased significantly at 1.1% per millimetre increase in the abdominal aortic aneurysm diameter (P= 0.0005). Furthermore, the rates of type Ia endoleak development (7% vs. 1.2%, P< 0.001) and requirement for reintervention (13.3% vs. 9.7%, P< 0.001) were higher in those treated outside the IFU (challenging neck group). CONCLUSIONS: Treatment with the Excluder AAA Endograft outside the IFU was associated with higher 5-year mortality values, increased type Ia endoleak development rates, and a greater need for reintervention compared with treatment within the IFU. This reiterates that fenestrated and open treatments should be strongly considered in cases with aortic neck anatomies outside the IFU. Infrarenal endovascular intervention outside the IFU should only be used when there is no alternative, with meticulous procedural planning and intervention to promote satisfactory outcomes.

The oral health status of patients with peripheral vascular disorders: A systematic review.

OBJECTIVES: Periodontal disease and tooth loss were found to be associated with several peripheral vascular disorders. Nonetheless, an evaluation of the literature on the broader domains of oral health in individuals with peripheral vascular disorders is lacking. This systematic review aims to collate the current evidence on the oral health status of individuals with peripheral vascular disorders. METHODS: Five electronic databases were searched for studies assessing oral health parameters in individuals with peripheral vascular disorders. Outcome measures considered were periodontal health, dentition status, caries indices, oral prostheses, oral pathologies and oral hygiene behaviours. The Newcastle-Ottawa scale was used to appraise the quality of the studies. RESULTS: From 3025 records identified, 24 studies involving 1232 participants with peripheral vascular disorders were included in this review. In nine studies, periodontitis was significantly more prevalent in peripheral vascular disorders compared to non-peripheral vascular disorders participants. A further six studies reported individuals with peripheral vascular disorders also had significantly fewer teeth and increased rates of edentulism. Only one study reported a higher incidence of dental caries in peripheral vascular disorders participants. Other aspects of oral health such as oral prosthesis, oral pathology and oral hygiene behaviours were seldom assessed. CONCLUSIONS: The scarcity of studies reporting on broader domains limited our ability to arrive at a conclusion regarding the oral health status of individuals with peripheral vascular disorders. Future studies ought to assess these domains in individuals with peripheral vascular disorders and controls to gain a more complete understanding of oral health and its potential association with peripheral vascular disorders.

Gallbladder necrosis and small bowel ischaemia following fenestrated endovascular aneurysm repair for juxtarenal abdominal aortic aneurysm: a case report.

Anatomical variation may result in unexpected complications after fenestrated endovascular aneurysm repair (FEVAR). We report a 78-year-old gentleman who was admitted for elective FEVAR procedure for a juxtarenal abdominal aortic aneurysm. Three days post-operatively, he deteriorated clinically. Computed tomography (CT) angiogram showed small bowel ischaemia and a replaced right hepatic artery originating from superior mesenteric artery. A necrotic gallbladder found during laparotomy required cholecystectomy following small bowel resection that required a relook for anastomosis and drainage of bile collection. He had prolonged ICU stay requiring treatment for multiple organ dysfunction then spent 4 weeks in hospital. Following multidisciplinary team approach in management of his complications during post-operative phase, he recovered well enough for rehabilitation and discharge home. Surveillance CT aorta at 1 month and 6 months post FEVAR showed satisfactory FEVAR appearance with no endoleak.

Mid-term outcomes of endovascular aneurysm repair in challenging aortic neck anatomy based on experience from the GREAT C3 registry.

BACKGROUND: The European C3 module of the Global Registry for Endovascular Aortic Treatment (GREAT) evaluates the outcome and deployment mechanism of the C3 Gore Excluder stent-graft. We aimed to assess the mid- to long-term durability of the C3 Gore Excluder stent-graft in the management of challenging aortic neck morphology, outside the instruction of use (IFU). METHODS: The prospectively collected data from GREAT were retrospectively analyzed. For each subject demographic, pre/intra- and postoperative variables were collected. The main outcomes measured were serious adverse events (device-related, cerebrovascular, cardiac, pulmonary, pulmonary embolism, limb ischemia, and renal complications) and re-intervention at the 6-year follow-up. In this study, outside IFU was defined as aortic neck length <15 mm and/or aortic neck angle >60°. RESULTS: A total of 399 subjects (86.7% male, mean age 73.9 years) were identified. Sixty-eight subjects (17%) from 11 recruiting sites underwent endovascular aneurysm repair (EVAR) outside IFU, and 399 devices were implanted. Of these, 47% had neck length <15 mm, 72.3% had neck angulation > 60°, and 21% had both. Mean follow-up duration was 53.5 months (SD=22.3). At the 6-year follow-up, the group with challenging anatomy required significantly more re-interventions (23.5% vs. 13.3%, P<0.05) and reported more serious adverse events (42.6% vs. 30.6%, P<0.005) than those within IFU. CONCLUSIONS: Midterm outcomes of the C3 Gore Excluder stent-graft are safe and effective within IFU. Outside IFU patients required significantly more all or device related re-interventions; however, they did not sustain significantly more serious adverse events.

Five-Year Outcomes of a Randomized Trial of Treatments for Varicose Veins.

BACKGROUND: Endovenous laser ablation and ultrasound-guided foam sclerotherapy are recommended alternatives to surgery for the treatment of primary varicose veins, but their long-term comparative effectiveness remains uncertain. METHODS: In a randomized, controlled trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of laser ablation, foam sclerotherapy, and surgery. Primary outcomes at 5 years were disease-specific quality of life and generic quality of life, as well as cost-effectiveness based on models of expected costs and quality-adjusted life-years (QALYs) gained that used data on participants' treatment costs and scores on the EuroQol EQ-5D questionnaire. RESULTS: Quality-of-life questionnaires were completed by 595 (75%) of the 798 trial participants. After adjustment for baseline scores and other covariates, scores on the Aberdeen Varicose Vein Questionnaire (on which scores range from 0 to 100, with lower scores indicating a better quality of life) were lower among patients who underwent laser ablation or surgery than among those who underwent foam sclerotherapy (effect size [adjusted differences between groups] for laser ablation vs. foam sclerotherapy, -2.86; 95% confidence interval [CI], -4.49 to -1.22; P<0.001; and for surgery vs. foam sclerotherapy, -2.60; 95% CI, -3.99 to -1.22; P<0.001). Generic quality-of-life measures did not differ among treatment groups. At a threshold willingness-to-pay ratio of £20,000 ($28,433 in U.S. dollars) per QALY, 77.2% of the cost-effectiveness model iterations favored laser ablation. In a two-way comparison between foam sclerotherapy and surgery, 54.5% of the model iterations favored surgery. CONCLUSIONS: In a randomized trial of treatments for varicose veins, disease-specific quality of life 5 years after treatment was better after laser ablation or surgery than after foam sclerotherapy. The majority of the probabilistic cost-effectiveness model iterations favored laser ablation at a willingness-to-pay ratio of £20,000 ($28,433) per QALY. (Funded by the National Institute for Health Research; CLASS Current Controlled Trials number, ISRCTN51995477.).

Thoracic endovascular repair (TEVAR) versus open surgery for blunt traumatic thoracic aortic injury.

BACKGROUND: Blunt traumatic thoracic aortic injury (BTAI) is a life-threatening surgical emergency associated with mortality up to 8000 per year, most commonly caused by rapid acceleration/deceleration injury sustained through motor vehicle accident and/or blunt thoracic trauma. BTAI has high pre-hospital mortality following the primary injury, with only 10% to 15% of patients surviving long enough to reach the hospital. Open surgical repair had remained the standard treatment option for BTAI since successfully introduced in 1959. However, with technological advances, thoracic endovascular repair (TEVAR) offers an alternative treatment option for BTAI. TEVAR is a less invasive surgical approach for management of these already critical patients; many reports have described favourable early outcomes.Thoracic endovascular repair may appear to be superior to open repair for treatment of BTAI. However, its long-term results and efficacy remain unknown. No randomised controlled trials (RCTs) have provided evidence to support the superiority of the endovascular approach versus open repair in the treatment of BTAI. This review aims to address this matter. This is an update of a review first published in 2015. OBJECTIVES: To determine whether use of thoracic endovascular repair (TEVAR) for treatment of blunt traumatic thoracic aortic injury (BTAI) is associated with reduced mortality and morbidity when compared with conventional open surgery. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL and AMED databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 20 August 2018. SELECTION CRITERIA: We considered all published and unpublished randomised controlled trials (RCTs) comparing TEVAR and open surgery for BTAI. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed all RCTs identified by the Cochrane Vascular Information Specialist. MAIN RESULTS: We found no RCTs that met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: We found no RCTs conducted to determine whether use of TEVAR for the treatment of BTAI is associated with reduced mortality and morbidity when compared to conventional open repair. Hence, we are unable to provide any evidence to guide the treatment option for this life-threatening condition. To perform a randomised controlled trial to clarify the optimal management of BTAI would be highly challenging due to the natural history of the condition. Despite the lack of RCT evidence, clinicians are moving forward with endovascular treatment of BTAI on the basis of meta-analyses of cohort studies and large clinical series.

Extracorporeal shock wave therapy for the healing and management of venous leg ulcers.

BACKGROUND: Leg ulcers are chronic wounds of the lower leg, caused by poor blood flow, that can take a long time to heal. The pooling of blood in the veins can damage the skin and surrounding tissues, causing an ulcer to form. Venous leg ulcers are associated with impaired quality of life, reduced mobility, pain, stress and loss of dignity. The standard treatment for venous leg ulcers is compression bandages or stockings. Shock wave therapy may aid the healing of these wounds through the promotion of angiogenesis (the formation and development of blood vessels) and reduction of inflammation, though this process is poorly understood at present. OBJECTIVES: To assess the effects of extracorporeal shock wave therapy on the healing and management of venous leg ulceration. SEARCH METHODS: In April 2018 we searched the Cochrane Wounds Specialised Register; the Cochrane Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE (including In-Process & Other Non-Indexed Citations); Ovid Embase and EBSCO CINAHL Plus. We also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses and health technology reports to identify additional studies. We applied no restrictions with respect to language, date of publication or study setting. SELECTION CRITERIA: We considered all published and unpublished randomised controlled trials (RCTs) assessing the effectiveness of extracorporeal shock wave therapy in the healing and management of venous leg ulceration. DATA COLLECTION AND ANALYSIS: Two review authors independently performed study selection. We planned that two review authors would also assess the risk of bias of included studies, extract study data and rate the certainty of the evidence using GRADE. MAIN RESULTS: We found no RCTs that met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: We found no RCTs assessing the effectiveness of extracorporeal shock wave therapy in the healing and management of venous leg ulceration. The lack of high-quality evidence in this area highlights a gap in research and may serve to justify the need for further research and evidence to provide guidance concerning the use of this treatment option for this condition. Future trials should be of clear design and include concomitant use of the current best practice treatment, multilayer compression therapy. Recruitment should aspire to best represent patients seen in clinical practice and patient-related outcome measures should be included in study design.

Clinical Agreement between Nurses in the Ultrasound Measurement of Abdominal Aortic Diameter within a National Screening Programme.

BACKGROUND: Accurate measurement is central to abdominal aortic aneurysm screening, but information concerning differences between observers using modern ultrasound devices is lacking. Our aim was to assess clinical agreement among nurses within a national screening programme. METHODS: Between-observer repeatability was assessed among 2 pairs of nurses (A & B and C & D) screening a consecutive series of men at a single-community clinic in Grampian, Scotland. All 4 nurses used the same ultrasound device (GE-LOGIQe 1.5-4.6 MHz curvilinear probe) to measure maximal infrarenal inner-to-inner (ITI) anteroposterior diameter in longitudinal and transverse planes. Nurses alternated in their measurements and were blinded to their partners' measurements. Participants remained supine while "double-scanned." Clinical agreement was assessed as twice the standard deviation (2 SD) of mean differences. Analysis was undertaken using IBM-SPSS-Statistics (version 22) using the Bland-Altman "limits of agreement" (95% LoA) approach (mean difference ±2 SD) and related plots. RESULTS: A total of 63 consecutive men underwent assessment (30 men by nurses A & B; 33 men by nurses C & D). Mean age 65.5 years, brachial blood pressure 145/88 mm Hg, current smokers 14%, never smoked 41%, diabetic 18%, arterial disease 11%, daily aspirin 16%, antihypertensives 35%, and statin therapy 44%. Mean aortic diameter (ITI) was 1.81 centimeters (cm; range 1.28-2.45; SD 0.18). Pooled mean differences between nurses was 0.05 cm (95% confidence interval 0.02-0.08); 2 SD ± 0.23 with 95% LoA -0.18 to 0.28 cm. Repeatability was similar in both planes and for both pairs of nurses. CONCLUSIONS: Nurses can achieve a high level of agreement in the measurement of aortic diameter in a routine clinical setting.

Thoracic endovascular repair (TEVAR) versus open surgery for blunt traumatic thoracic aortic injury.

BACKGROUND: Blunt traumatic thoracic aortic injury (BTAI) is a life-threatening surgical emergency associated with mortality up to 8000 per year, most commonly caused by rapid acceleration/deceleration injury sustained through motor vehicle accident and/or blunt thoracic trauma. BTAI has high pre-hospital mortality following the primary injury, with only 10% to 15% of patients surviving long enough to reach the hospital. Open surgical repair had remained the standard treatment option for BTAI since successfully introduced in 1959. However, with technological advances, thoracic endovascular repair (TEVAR) offers an alternative treatment option for BTAI. TEVAR is a less invasive surgical approach for management of these already critical patients; many reports have described favourable early outcomes.Thoracic endovascular repair may appear to be superior to open repair for treatment of BTAI. However, its long-term results and efficacy remain unknown. No randomised controlled trials (RCTs) have provided evidence to support the superiority of the endovascular approach versus open repair in the treatment of BTAI. This review aims to address this matter. OBJECTIVES: To determine whether use of TEVAR for treatment of BTAI is associated with reduced mortality and morbidity when compared with conventional open surgery. SEARCH METHODS: The Cochrane Vascular Trials Search Co-ordinator searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 7) and clinical trials databases for details of ongoing and unpublished studies. SELECTION CRITERIA: We considered all published and unpublished randomised controlled trials (RCTs) comparing TEVAR and open surgery for BTAI. DATA COLLECTION AND ANALYSIS: Two review authors independently reviewed all RCTs identified by the Trials Search Co-ordinator. MAIN RESULTS: We found no RCTs that met the inclusion criteria for this review. AUTHORS' CONCLUSIONS: We found no RCTs conducted to determine whether use of TEVAR for the treatment of BTAI is associated with reduced mortality and morbidity when compared to conventional open repair. Hence, we are unable to provide any evidence to guide the treatment option for this life-threatening condition. To perform a randomised controlled trial to clarify the optimal management of BTAI would be highly challenging due to the natural history of the condition. Despite the lack of RCT evidence, clinicians are moving forward with endovascular treatment of BTAI on the basis of meta-analyses and large clinical series.

Clinical effectiveness and cost-effectiveness of foam sclerotherapy, endovenous laser ablation and surgery for varicose veins: results from the Comparison of LAser, Surgery and foam Sclerotherapy (CLASS) randomised controlled trial.

BACKGROUND: Foam sclerotherapy (foam) and endovenous laser ablation (EVLA) have emerged as alternative treatments to surgery for patients with varicose veins, but uncertainty exists regarding their effectiveness in the medium to longer term. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of foam, EVLA and surgery for the treatment of varicose veins. DESIGN: A parallel-group randomised controlled trial (RCT) without blinding, and economic modelling evaluation. SETTING: Eleven UK specialist vascular centres. PARTICIPANTS: Seven hundred and ninety-eight patients with primary varicose veins (foam, n = 292; surgery, n = 294; EVLA, n = 212). INTERVENTIONS: Patients were randomised between all three treatment options (eight centres) or between foam and surgery (three centres). PRIMARY OUTCOME MEASURES: Disease-specific [Aberdeen Varicose Vein Questionnaire (AVVQ)] and generic [European Quality of Life-5 Dimensions (EQ-5D), Short Form questionnaire-36 items (SF-36) physical and mental component scores] quality of life (QoL) at 6 months. Cost-effectiveness as cost per quality-adjusted life-year (QALY) gained. SECONDARY OUTCOME MEASURES: Quality of life at 6 weeks; residual varicose veins; Venous Clinical Severity Score (VCSS); complication rates; return to normal activity; truncal vein ablation rates; and costs. RESULTS: The results appear generalisable in that participants' baseline characteristics (apart from a lower-than-expected proportion of females) and post-treatment improvement in outcomes were comparable with those in other RCTs. The health gain achieved in the AVVQ with foam was significantly lower than with surgery at 6 months [effect size -1.74, 95% confidence interval (CI) -2.97 to -0.50; p = 0.006], but was similar to that achieved with EVLA. The health gain in SF-36 mental component score for foam was worse than that for EVLA (effect size 1.54, 95% CI 0.01 to 3.06; p = 0.048) but similar to that for surgery. There were no differences in EQ-5D or SF-36 component scores in the surgery versus foam or surgery versus EVLA comparisons at 6 months. The trial-based cost-effectiveness analysis showed that, at 6 months, foam had the highest probability of being considered cost-effective at a ceiling willingness-to-pay ratio of £20,000 per QALY. EVLA was found to cost £26,107 per QALY gained versus foam, and was less costly and generated slightly more QALYs than surgery. Markov modelling using trial costs and the limited recurrence data available suggested that, at 5 years, EVLA had the highest probability (≈ 79%) of being cost-effective at conventional thresholds, followed by foam (≈ 17%) and surgery (≈ 5%). With regard to secondary outcomes, health gains at 6 weeks (p < 0.005) were greater for EVLA than for foam (EQ-5D, p = 0.004). There were fewer procedural complications in the EVLA group (1%) than after foam (7%) and surgery (8%) (p < 0.001). Participants returned to a wide range of behaviours more quickly following foam or EVLA than following surgery (p < 0.05). There were no differences in VCSS between the three treatments. Truncal ablation rates were higher for surgery (p < 0.001) and EVLA (p < 0.001) than for foam, and were similar for surgery and EVLA. CONCLUSIONS: Considerations of both the 6-month clinical outcomes and the estimated 5-year cost-effectiveness suggest that EVLA should be considered as the treatment of choice for suitable patients. FUTURE WORK: Five-year trial results are currently being evaluated to compare the cost-effectiveness of foam, surgery and EVLA, and to determine the recurrence rates following each treatment. This trial has highlighted the need for long-term outcome data from RCTs on QoL, recurrence rates and costs for foam sclerotherapy and other endovenous techniques compared against each other and against surgery. TRIAL REGISTRATION: Current Controlled Trials ISRCTN51995477. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 27. See the NIHR Journals Library website for further project information.

A randomized trial comparing treatments for varicose veins.

BACKGROUND: Ultrasound-guided foam sclerotherapy and endovenous laser ablation are widely used alternatives to surgery for the treatment of varicose veins, but their comparative effectiveness and safety remain uncertain. METHODS: In a randomized trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of foam, laser, and surgical treatments. Primary outcomes at 6 months were disease-specific quality of life and generic quality of life, as measured on several scales. Secondary outcomes included complications and measures of clinical success. RESULTS: After adjustment for baseline scores and other covariates, the mean disease-specific quality of life was slightly worse after treatment with foam than after surgery (P=0.006) but was similar in the laser and surgery groups. There were no significant differences between the surgery group and the foam or the laser group in measures of generic quality of life. The frequency of procedural complications was similar in the foam group (6%) and the surgery group (7%) but was lower in the laser group (1%) than in the surgery group (P<0.001); the frequency of serious adverse events (approximately 3%) was similar among the groups. Measures of clinical success were similar among the groups, but successful ablation of the main trunks of the saphenous vein was less common in the foam group than in the surgery group (P<0.001). CONCLUSIONS: Quality-of-life measures were generally similar among the study groups, with the exception of a slightly worse disease-specific quality of life in the foam group than in the surgery group. All treatments had similar clinical efficacy, but complications were less frequent after laser treatment and ablation rates were lower after foam treatment. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN51995477.).

Pseudoaneurysm of the sural artery: a rare complication of lower limb angioplasty.

INTRODUCTION: Percutaneous transluminal angioplasty (PTA) is a common therapeutic option for the treatment of peripheral vascular disease. Pseudoaneurysm at the puncture site is a well-documented complication in patients. CASE PRESENTATION: This case report describes a patient who presented to hospital several days following a left superficial femoral and popliteal artery PTA with lower limb pain and swelling. The working diagnosis included a deep vein thrombosis based on the Wells criteria. However, a combination of a duplex scan and computed tomography angiography confirmed a clinically rare occurrence of pseudoaneurysm of the sural artery, a branch of the popliteal artery. This was managed successfully with a thrombin injection, leading to complete resolution of the patient's symptoms. CONCLUSION: This case highlights the importance of the technical aspects of performing a PTA. We believe that the guide-wire position was not confirmed to be completely in the popliteal artery upon inflation of the balloon.

Effect of Omega-3 fatty acid supplementation on markers of platelet and endothelial function in patients with peripheral arterial disease.

OBJECTIVE: Omega-3 fatty acids have been shown to reduce platelet and endothelial activation in patients with or at risk of cardiac disease. We aimed to determine if Omega-3 fatty acid supplementation in addition to best medical therapy can reduce the increased platelet and endothelial activity that is present in patients with intermittent claudication. METHODS: One hundred and fifty patients who were receiving aspirin and statin therapy were recruited into a randomised cross-over double blind study involving 6 week supplementation with OMACOR fish oil (850-882 mg eicosapentaenoic and docosahexaenoic acid) versus placebo. A 12 week washout period occurred between treatments. Patients with diabetes were excluded. For each outcome a random effects model was fitted in which treatment and period were fixed effects and patients were random effects. RESULTS: Omega-3 supplementation had no effect on the primary outcome measure von Willebrand factor. Similarly Omega-3 supplementation resulted in no change in unstimulated or stimulated P-selectin expression and fibrinogen binding, or platelet aggregation (Ultegra point of care). Pulse wave velocity was also unchanged. High-sensitivity C-reactive protein, s-ICAM and IL-6 were also unchanged. CONCLUSION: Supplementation with Omega-3 fatty acids had no affect on platelet and endothelial activation or markers of inflammation in patients with peripheral arterial disease.

Endovascular stents for intermittent claudication.

BACKGROUND: Endovascular stents have been suggested as a means to improve the patency of arteries after angioplasty in patients with intermittent claudication. This is an update of a Cochrane review published in 2002. OBJECTIVES: The null hypothesis to be tested by this review is that for individuals with claudication the use of an endovascular stent, in addition to percutaneous transluminal angioplasty, does not improve symptoms of life-style limiting claudication when compared to percutaneous angioplasty alone. SEARCH STRATEGY: For this update the Cochrane Peripheral Vascular Diseases Group searched their Specialised Register (last searched August 2009) and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (last searched 2009, Issue 3). SELECTION CRITERIA: Randomised trials comparing angioplasty alone versus angioplasty with endovascular stents in patients with intermittent claudication. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted the data. Only published trial data were used but unpublished data were sought for the update. Effectiveness was measured by the pre-defined primary outcome measures restenosis or reocclusion rates and maximum walking distance. MAIN RESULTS: Two studies were included involving a total of 104 participants. Both studies included only individuals with femoro-popliteal disease. They compared angioplasty and stenting with the Palmaz stent against angioplasty alone. Although one study showed a slight statistical advantage in arterial patency after angioplasty alone, this was not found when the two studies were combined. No differences in the secondary outcomes were detected in either study. AUTHORS' CONCLUSIONS: The small number of relevant studies identified together with the small sample sizes and methodological weaknesses severely limit the usefulness of this review in guiding practice. The results from larger multicentre trials are needed.

Does knee replacement surgery lead to chronic limb ischemia?

Total knee replacement (TKR) may be associated with chronic limb ischemia (CLI) due to arterial injury intraoperatively. The aim of this study was to determine the incidence of CLI after TKR surgery. Patients who received a unilateral TKR in 2003-2004 were identified from our database. Patients with diabetes mellitus and preexisting peripheral arterial disease were excluded. Patient assessment was by collection of demographic details, completion of the Oxford Knee Score, Short Form-12 Health Survey, and King's College Hospital's Vascular Quality of Life Questionnaire, and measurement of the ankle brachial pressure index (ABPI). Of the 209 eligible patients, 86 (41%) participated (median age, 73 years; 50% male). Five (5.8%) patients had a reduced ABPI compared with population norms of 4.6 to 7%. Patients with reduced ABPI measurements had higher Oxford Knee Scores, but no relationships between other variables were demonstrated. TKR surgery does not appear to increase the risk of CLI.

Randomized controlled trial of aspirin and clopidogrel versus aspirin and placebo on markers of smooth muscle proliferation before and after peripheral angioplasty.

OBJECTIVE: In peripheral arterial disease (PAD) patients, a limiting factor in the success of percutaneous transluminal angioplasty (PTA) is the development of restenosis secondary to vascular smooth muscle cell (SMC) proliferation. Following endothelial damage and platelet activation, there is release of factors and adhesion molecules which affect SMC proliferation. The aim of this study was to determine the effect of combination antiplatelet therapy (clopidogrel and aspirin compared with aspirin and placebo) on the ability of plasma from PAD patients undergoing PTA to stimulate SMCs in vitro. We further aimed to investigate the effect of combination treatment on the levels of circulating adhesion molecules and factors, which are known to mediate SMC proliferation in experimental models. METHODS: Fifty patients were randomized to receive blinded clopidogrel or placebo, for thirty days, in addition to their daily 75 mg aspirin. To measure proliferative capacity, diluted plasma was incubated for 15 minutes with 24 hour-growth-arrested rat vascular smooth muscle cells, and extracellular regulated kinase (ERK)1/2 activation was analyzed by Western blotting at baseline, one hour pre-PTA, one hour, 24 hours and 30 days post-PTA. Plasma platelet-derived growth factor (PDGF), sE-selectin, intracellular adhesion molecule-1 (sICAM-1), and von Willebrand factor (vWF) were measured by ELISA, at the same five timepoints. Platelet activation was measured by flow cytometry of ADP-stimulated platelet fibrinogen binding at baseline and one hour post-PTA. RESULTS: ADP-stimulated platelet fibrinogen binding was significantly inhibited by clopidogrel before and after PTA. ERK 1/2 activation was significantly increased post-PTA in both the aspirin/clopidogrel and aspirin/placebo groups (P < .001). There was a statistically significant decrease in PDGF (P = .004), and increase in vWF (P = .026), following loading with clopidogrel. sICAM-1 levels significantly decreased (P = .016) in the aspirin/placebo group following PTA. There were no other significant changes and also there was no statistically significant difference between the two treatment groups for each of ERK 1/2, sICAM-1, sE-selectin, or vWF. CONCLUSIONS: This is the first study to show in-vitro ERK 1/2 activation (a surrogate marker of SMC proliferation) increases post-PTA. Combination antiplatelet therapy had no significant effect on this, although it did reduce PDGF. Further work is required to evaluate potential therapeutic treatments, which may reduce peripheral PTA-induced smooth muscle cell activation. CLINICAL RELEVANCE: High rates of restenosis remain the major limitation of peripheral arterial angioplasty and stenting.The restenotic lesion occurs secondary to platelet activation, released circulating factors, and subsequent smooth musclecell proliferation and migration into the intima. Methods to limit the restenotic lesion are poorly understood. This paperinvestigates the effect of PTA on smooth muscle cell activation and the release of factors in plasma which mediate SMCproliferation. It also examines the effect of combination antiplatelet therapy as a potential therapeutic strategy.

N-terminal pro B-type natriuretic peptide is an independent predictor of postoperative myocardial injury in patients undergoing major vascular surgery.

OBJECTIVE: Myocardial ischemia and infarction after surgery remain leading causes of morbidity and mortality in patients undergoing major vascular surgery. B-type natriuretic peptide has been shown to predict early postoperative cardiac events in patients undergoing major noncardiac surgery. We aimed to determine if N-terminal pro B-type natriuretic peptide (NT-pro-BNP), with its longer half-life and greater plasma stability, can predict postoperative myocardial injury in vascular patients. METHODS: Recruited were 136 patients undergoing elective surgery for subcritical limb ischemia or abdominal aortic aneurysm (AAA) repair. Plasma NT-pro-BNP was measured preoperatively, and troponin-I was measured immediately after surgery and on postoperative days 1, 2, 3, and 5. RESULTS: Twenty-eight patients (20%) sustained postoperative myocardial injury (troponin-I rise of >0.1 ng/mL). The median NT-pro-BNP level of those with myocardial injury was significantly higher than those who did not (380 pg/mL [interquartile range (IQR), 223-967] vs 209 pg/mL [109-363]; P = .003). NT-pro-BNP predicted this outcome with an area under the receiver operating characteristic (ROC) curve of 68% (95% confidence interval [CI] 0.56%-0.78%). In a multivariate analysis, a NT-pro-BNP value of >/=308 pg/mL (the optimal ROC curve-derived cutoff) was associated with an increased incidence of myocardial injury (odds ratio, 3.4; 95% CI, 1.41-9.09, P =.01). CONCLUSION: Elevated preoperative plasma NT-pro-BNP levels independently predict postoperative myocardial injury, which is associated with adverse outcome in the short- and long-term regardless of the presence of symptoms of acute coronary syndrome.

Platelet activation increases with the severity of peripheral arterial disease: implications for clinical management.

INTRODUCTION: Patients with peripheral arterial disease (PAD) have increased mortality from cardiovascular events compared with age and sex matched controls Platelets play a major role in atherosclerosis and thrombotic vascular events. Platelet reactivity is increased in patients with PAD compared with healthy controls. We aimed to determine the relationship, if any, between platelet activation and severity of disease. METHODS AND RESULTS: One hundred eighty-two patients with intermittent claudication (IC) or subcritical limb ischemia (SLI), defined as the presence of rest pain or ulceration, had the following investigations performed: platelet P-selectin expression and bound fibrinogen by flow cytometric analysis and platelet aggregation using the rapid platelet function assay with arachidonic acid (AA) and thrombin receptor activation peptide (TRAP) as agonists. Patients with SLI compared with IC had significantly enhanced ADP stimulated P-selectin expression (median 42.45% [inter-quartile range 33.32% to 58.5%] vs 35.2% [26.07% to 46.32%], P = .002) and bound fibrinogen (73.7% [54.3% to 83.2%] vs 63.7% [43.8% to 76.5%], P = .001). TRAP stimulated aggregation was higher (207 [153 to 238] PAU vs 183[155 to 199] PAU, P = .04) but AA mediated aggregation was not significantly different. An ankle-brachial pressure index (ABPI) of less than 0.6 was associated with increased ADP stimulated P-selectin and bound fibrinogen (P < .05). ABPI correlated inversely with ADP stimulated P-selectin expression (r = -0.228, P = .003), ADP stimulated fibrinogen binding (r = -0.156, P = .043) and TRAP stimulated aggregation (r = -0.179, P = .04). CONCLUSION: We have demonstrated for the first time that progression of severity of PAD is not only reflected by symptoms, signs, and ABPI but also by increased platelet activity as assessed by both flow cytometry and aggregation. As patients with more severe PAD have increased cardiovascular mortality, our findings suggest that new strategies for platelet inhibitory therapy are indicated in these patients.