A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2): an open-label, randomised, multicentre, phase 3 trial.

BACKGROUND: Chronic limb-threatening ischaemia is the severest manifestation of peripheral arterial disease and presents with ischaemic pain at rest or tissue loss (ulceration, gangrene, or both), or both. We compared the effectiveness of a vein bypass first with a best endovascular treatment first revascularisation strategy in terms of preventing major amputation and death in patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. METHODS: Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL)-2 was an open-label, pragmatic, multicentre, phase 3, randomised trial done at 41 vascular surgery units in the UK (n=39), Sweden (n=1), and Denmark (n=1). Eligible patients were those who presented to hospital-based vascular surgery units with chronic limb-threatening ischaemia due to atherosclerotic disease and who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. Participants were randomly assigned (1:1) to receive either vein bypass (vein bypass group) or best endovascular treatment (best endovascular treatment group) as their first revascularisation procedure through a secure online randomisation system. Participants were excluded if they had ischaemic pain or tissue loss considered not to be primarily due to atherosclerotic peripheral artery disease. Most vein bypasses used the great saphenous vein and originated from the common or superficial femoral arteries. Most endovascular interventions comprised plain balloon angioplasty with selective use of plain or drug eluting stents. Participants were followed up for a minimum of 2 years. Data were collected locally at participating centres. In England, Wales, and Sweden, centralised databases were used to collect information on amputations and deaths. Data were analysed centrally at the Birmingham Clinical Trials Unit. The primary outcome was amputation-free survival defined as time to first major (above the ankle) amputation or death from any cause measured in the intention-to-treat population. Safety was assessed by monitoring serious adverse events up to 30-days after first revascularisation. The trial is registered with the ISRCTN registry, ISRCTN27728689. FINDINGS: Between July 22, 2014, and Nov 30, 2020, 345 participants (65 [19%] women and 280 [81%] men; median age 72·5 years [62·7-79·3]) with chronic limb-threatening ischaemia were enrolled in the trial and randomly assigned: 172 (50%) to the vein bypass group and 173 (50%) to the best endovascular treatment group. Major amputation or death occurred in 108 (63%) of 172 patients in the vein bypass group and 92 (53%) of 173 patients in the best endovascular treatment group (adjusted hazard ratio [HR] 1·35 [95% CI 1·02-1·80]; p=0·037). 91 (53%) of 172 patients in the vein bypass group and 77 (45%) of 173 patients in the best endovascular treatment group died (adjusted HR 1·37 [95% CI 1·00-1·87]). In both groups the most common causes of morbidity and death, including that occurring within 30 days of their first revascularisation, were cardiovascular (61 deaths in the vein bypass group and 49 in the best endovascular treatment group) and respiratory events (25 deaths in the vein bypass group and 23 in the best endovascular treatment group; number of cardiovascular and respiratory deaths were not mutually exclusive). INTERPRETATION: In the BASIL-2 trial, a best endovascular treatment first revascularisation strategy was associated with a better amputation-free survival, which was largely driven by fewer deaths in the best endovascular treatment group. These data suggest that more patients with chronic limb-threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion should be considered for a best endovascular treatment first revascularisation strategy. FUNDING: UK National Institute of Health Research Health Technology Programme.

Meta-analysis of direct surgical versus endovascular revascularization for aortoiliac occlusive disease.

OBJECTIVE: There is a paucity of good-quality evidence comparing direct surgical (DS) with endovascular/hybrid (EVH) revascularization for aortoiliac occlusive disease (AIOD). We aimed to perform a meta-analysis of studies comparing DS and EVH revascularization for AIOD. METHODS: PubMed, Ovid MEDLINE, Cochrane, and Embase databases were searched for studies comparing DS and EVH revascularization for AIOD from 2000 to 2018. Risk of bias assessment was performed using the Methodological Index for Non-Randomized Studies. Demographics, clinical presentation, and comorbidities of the two groups were compared. Kaplan-Meier curves from selected studies were digitized with WebPlotDigitizer. Meta-analysis was conducted using Review Manager, and outcome measures were compared. Subgroup analysis was performed for primary patency in the EVH group. RESULTS: Eleven observational studies were identified comparing a sample of 4030 patients. The median Methodological Index for Non-Randomized Studies score was 19 of 24. A total of 1679 and 2351 patients underwent DS and EVH techniques, respectively. No significant difference was found between means for sex, claudication, rest pain, tissue loss, preoperative ankle-brachial pressure index, and TransAtlantic Inter-Society Consensus C and D lesions in the two groups averaged across studies. However, the DS group had significantly younger patients (average age, 61.83 vs 66.77; P = .0011). The risk factors of the two groups, such as smoking, diabetes, ischemic heart disease, hypertension, hyperlipidemia, renal failure, and chronic lung disease, were comparable. Average hospital stay was significantly higher for the DS group (7.76 days vs 3.12 days; P = .025). Change in ankle-brachial pressure index, 30-day mortality, and 30-day graft/stent thrombosis were not significantly different for the groups. Overall, primary patency for a median follow-up of 50 months favored the DS group (hazard ratio [HR], 0.51; confidence interval [CI], 0.36-0.73; P = .0002). There was moderate heterogeneity among studies (I2 = 46%). The HR for the subgroup for which endovascular procedures were combined with common femoral endarterectomy was 0.43 compared with 0.88 for endovascular revascularization alone. Limb salvage was similar in both groups (HR, 1.10; CI, 0.74-1.64; P = .63), but overall survival after the procedure favored the DS group (HR, 0.75; CI, 0.60-0.94; P = .01; I2 = 0%). CONCLUSIONS: Moderate-quality studies showed that DS revascularization had significantly better primary patency than EVH revascularization for AIOD, although DS patients were younger and may have differed on other confounding variables. Both techniques had similar limb salvage rates, and the primary patency was better for endovascular revascularization combined with common femoral endarterectomy than for endovascular revascularization alone.

Artery Ligation for Infected Femoral Pseudoaneurysms Does Carry a High Risk of Major Amputation.

BACKGROUND: Arterial ligation has been described in the literature as a safe and effective procedure with a relatively low number of patients requiring major amputations. METHODS: We performed a retrospective analysis of a prospectively held database of all patients who underwent arterial ligation for infected femoral pseudoaneurysms due to chronic intravenous drug abuse from January 2012 to March 2018. Information recorded for each patient included age, gender, blood investigations, microbiologic results, diagnostic modality, operative details, outcome of surgery, postoperative complications, and follow-up. RESULTS: There were 25 patients identified, with 2 of them undergoing bilateral ligations. It was more common in men (4:1), and the mean age at presentation was 39.7 years (standard deviation 8.2 y). Nine patients underwent major limb amputation for severe limb ischemia (7 transfemoral amputations and two 53 hip disarticulation). Average hospital stay was 24 days, and there was no mortality. We found a trend with a higher level of arterial ligation, leading to a higher rate of amputation. CONCLUSIONS: Our study is the first to show that there is a trend toward a higher risk of amputation with a higher level of ligation in this cohort of patients, and therefore, we suggest avoidance of external iliac artery ligation even at the most distal part just under the ligament, leaving the circumflex iliac vessel in circuit. Arterial ligation also carries a higher risk of major amputation than previously reported.

Prior Radiological Investigations in 65-Year-Old Men Screened for AAA.

BACKGROUND: The National Health Service abdominal aortic aneurysm screening programme (NAAASP) is now fully operational. Those who have previously been formally investigated for abdominal aortic aneurysm (AAA) are excluded; however, many patients undergo radiological investigation of the abdomen for other reasons. Such practices may find incidental AAA which may be eroding the performance of the NAAASP. We investigated the rates of preinvestigation before invitation to screening in our local AAA screening programme. METHODS: Electronic patient records were retrospectively reviewed for all patients called between March 2013 and February 2016 in 1 local AAA screening programme. Their records were interrogated to identify any abdominal imaging within 5 years of their invitation to screening. RESULTS: Two thousand six hundred thirty-eight men were invited for screening; of these, 563 (21.3%) had been "prescreened". Median time between prescreening and screening was 19 months (0-60 months). Ultrasound abdomen was the most prevalent at 248 (44.0%). Two thousand two hundred forty-three (85.0%) men attended screening, and 6 (0.27%) were excluded for known AAA. Prevalence of AAA was 1.8% (n = 41). Of these, 15 (36.6%) had prior investigation with 6 (40.0%) having AAA diagnosed. Therefore, 9 (22.0%) had potential missed AAA on "prescreening" (mean diameter 35 mm [30-45], mean time lapse between investigation and screening 21.1 months [1-49]). Incidence of missed aneurysm in the "prescreened" cohort was 1.6% (9/563). CONCLUSIONS: Large numbers of men invited for AAA screening have undergone preinvestigation of their abdominal aorta, with 60% of the present AAA being missed. Reliance on incidental detection of AAA would leave many patients undiagnosed in the community-at risk of future rupture.

A new technique to explant an infected aortic endograft.

The management of an infected aortic endograft can be challenging both operatively and clinically. Although aortic endograft infection is rare, the incidence is likely to increase in the coming years because of ever rising numbers of endovascular aneurysm repairs. Definitive management involves the removal of the endograft through laparotomy. Removal of the graft is technically challenging; no manufacturer's device is available to assist in disengagement of barbed hooks that hold the endograft in position. We present a new technique using the disposable proctoscope as a device to facilitate safe removal of the endograft with minimal damage to the aortic wall.

Popliteal endarterectomy for localized popliteal artery disease.

BACKGROUND: The incidence of localized popliteal disease is rare. Currently, patients presenting with symptomatic popliteal disease are offered femoropopliteal or tibial bypass if the disease is not amenable to radiologic intervention. We feel that popliteal endarterectomy by means of a posterior approach with patch angioplasty as a primary procedure is a viable surgical option. Our aim was to assess the durability of popliteal endarterectomy in patients with localized popliteal disease, in which radiologic intervention is not feasible. METHODS: This is a retrospective review of all patients who underwent popliteal endarterectomy for localized popliteal disease in our institution over the past 3 years. All patients underwent a preoperative assessment with computed tomography angiography. Angioplasty was attempted in all patients before surgical intervention. Patency was assessed radiologically 6 weeks after operation. Patients had follow-up appointments at intervals of 6 weeks, 3 months, 6 months, and a year after surgery. RESULTS: A total of 7 patients (5 men and 2 women) underwent popliteal endarterectomy. The mean age was 64.3 years, with a mean follow-up period of 9.9 months (range, 2-26 months). Four patients were treated for activity-limiting claudication (<100 yards), whereas 3 patients were treated for ischemic rest pain. The procedural success rate was 100% without mortalities or in-hospital morbidities. Symptomatic resolution was achieved in 6 patients. One patient occluded 1 month after endarterectomy because of a critical stenosis at the tibial bifurcation. CONCLUSIONS: Popliteal endarterectomy through posterior approach is advantageous in managing popliteal artery pathology restricted to the popliteal fossa. It is safe with good short-term results.

Embryo vitrification using a novel semi-automated closed system yields in vitro outcomes equivalent to the manual Cryotop method.

STUDY QUESTION: Can the equilibration steps prior to embryo vitrification be automated? SUMMARY ANSWER: We have developed the 'Gavi' system which automatically performs equilibration steps before closed system vitrification on up to four embryos at a time and gives in vitro outcomes equivalent to the manual Cryotop method. WHAT IS KNOWN ALREADY: Embryo cryopreservation is an essential component of a successful assisted reproduction clinic, with vitrification providing excellent embryo survival and pregnancy outcomes. However, vitrification is a manual, labour-intensive and highly skilled procedure, and results can vary between embryologists and clinics. A closed system whereby the embryo does not come in direct contact with liquid nitrogen is preferred by many clinics and is a regulatory requirement in some countries. STUDY DESIGN, SIZE, DURATION: The Gavi system, an automation instrument with a novel closed system device, was used to equilibrate embryos prior to vitrification. Outcomes for embryos automatically processed with the Gavi system were compared with those processed with the manual Cryotop method and with fresh (non-vitrified) controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: The efficacy of the Gavi system (Alpha model) was assessed for mouse (Quackenbush Swiss and F1 C57BL/6J x CBA) zygotes, cleavage stage embryos and blastocysts, and for donated human vitrified-warmed blastocysts. The main outcomes assessed included recovery, survival and in vitro embryo development after vitrification-warming. Cooling and warming rates were measured using a thermocouple probe. MAIN RESULTS AND THE ROLE OF CHANCE: Mouse embryos vitrified after processing with the automated Gavi system achieved equivalent in vitro outcomes to that of Cryotop controls. For example, for mouse blastocysts both the Gavi system (n = 176) and manual Cryotop method (n = 172) gave a 99% recovery rate, of which 54 and 50%, respectively, progressed to fully hatched blastocysts 48 h after warming. The outcomes for human blastocysts processed with the Gavi system (n = 23) were also equivalent to Cryotop controls (n = 13) including 100% recovery for both groups, of which 17 and 15%, respectively, progressed to fully hatched blastocysts 48 h after warming. The cooling and warming rates achieved with the Gavi system were 14 136°C/min and 11 239°C/min, respectively. LIMITATIONS, REASONS FOR CAUTION: Testing of the Gavi system described here was limited to in vitro development of embryos from two mouse strains and a limited number of human embryos. Validation of Gavi system advanced production models is now required to confirm the success of semi-automated vitrification, including clinical evaluation of pregnancy outcomes from the transfer of Gavi vitrified-warmed human embryos. WIDER IMPLICATIONS OF THE FINDINGS: The Gavi system has the potential to revolutionize and standardize vitrification of embryos and oocytes. The success of the Gavi system shows that it is possible to semi-automate complicated labour-intensive ART methods and processes, and opens up the possibility for further improvements in clinical outcomes and efficiencies in the ART clinic. STUDY FUNDING/COMPETING INTERESTS: This study was funded by Genea Ltd. S.B., N.M.T., T.T.P., S.J.M., M.C.B. and T.S. are shareholders of Genea Ltd. E.V., C.H., C.L., S.R.L. and S.M.D. are shareholders of Planet Innovation Pty Ltd. The remaining authors are employees of either Genea Ltd. or Planet Innovation Pty Ltd.

Utility of a Multi-Marker Panel with Ultrasound for Enhanced Classification of Adnexal Mass.

Pre-surgical clinical assessment of an adnexal mass typically relies on transvaginal ultrasound for comprehensive morphological assessment, with further support provided by biomarker measurements and clinical evaluation. Whilst effective for masses that are obviously benign or malignant, a large proportion of masses remain sonographically indeterminate at surgical referral. As a consequence, post-surgical diagnoses of benign disease can outnumber malignancies up to 9-fold, while less than 50% of cancer cases receive a primary referral to a gynecological oncology specialist. We recently described a blood biomarker signature (multi-marker panel-MMP) that differentiated patients with benign from malignant ovarian disease with high accuracy. In this study, we have examined the use of the MMP, both individually and in combination with transvaginal ultrasound, as an alternative tool to CA-125 for enhanced decision making in the pre-surgical referral process.

ReClassification of Patients with Ambiguous CA125 for Optimised Pre-Surgical Triage.

Pre-surgical clinical assessment of an adnexal mass is a complex process, and ideally requires accurate and rapid identification of disease status. Gold standard biomarker CA125 is extensively used off-label for this purpose; however its performance is typically inadequate, particularly for the detection of early stage disease and discrimination between benign versus malignant status. We recently described a multi-marker panel (MMP) and associated risk index for the differentiation of benign from malignant ovarian disease. In this study we applied a net reclassification approach to assess the use of MMP index to rescue those cases where low CA125 incorrectly excludes cancer diagnoses, or where benign disease is incorrectly assessed as "high risk" due to elevated CA125. Reclassification of such patients is of significant value to assist in the timely and accurate referral for patients where CA125 titer is uninformative.

A Novel Predictive Multi-Marker Test for the Pre-Surgical Identification of Ovarian Cancer.

Ovarian cancer remains the most lethal of gynecological malignancies, with the 5-year survival below 50%. Currently there is no simple and effective pre-surgical diagnosis or triage for patients with malignancy, particularly those with early-stage or low-volume tumors. Recently we discovered that CXCL10 can be processed to an inactive form in ovarian cancers and that its measurement has diagnostic significance. In this study we evaluated the addition of processed CXCL10 to a biomarker panel for the discrimination of benign from malignant disease. Multiple biomarkers were measured in retrospectively collected plasma samples (n = 334) from patients diagnosed with benign or malignant disease, and a classifier model was developed using CA125, HE4, Il6 and CXCL10 (active and total). The model provided 95% sensitivity/95% specificity for discrimination of benign from malignant disease. Positive predictive performance exceeded that of "gold standard" scoring systems including CA125, RMI and ROMA% and was independent of menopausal status. In addition, 80% of stage I-II cancers in the cohort were correctly identified using the multi-marker scoring system. Our data suggest the multi-marker panel and associated scoring algorithm provides a useful measurement to assist in pre-surgical diagnosis and triage of patients with suspected ovarian cancer.

Patency of infra-inguinal vein grafts--effect of intraoperative Doppler assessment and a graft surveillance program.

OBJECTIVE: To assess the value of intraoperative graft flow and resistance measurements and a graft surveillance program to predict at-risk infra-inguinal bypass grafts. METHODS: Four hundred sixty-eight infra-inguinal bypass procedures performed between 1995-2006 underwent intraoperative measurement of graft flow and resistance using a Scimed OpDop. These data were correlated with graft outcome at six weeks. Two hundred fifty-four (73%) grafts were entered into a graft surveillance program and the effect of this on primary-assisted graft patency was assessed. RESULTS: Overall primary and primary-assisted graft patency was 81% and 83% at six weeks and 42% and 64% at three years. Grafts failing by six weeks had significantly lower flow (130.5 mL/min vs. 150.5 mL/min, P = .009) and higher resistance (0.67 peripheral resistance units (PRU) vs. 0.57 PRU, P = .004) than those remaining patent. However, OpDop measured flow and resistance was a poor predictor of graft failure in individual cases (area under ROC curve, 0.57). While there was no statistical difference in primary 18-month patency rates between grafts undergoing surveillance and those undergoing clinical follow up (55% vs. 76%, P = .133), primary-assisted 18-month patency rates were significantly higher in the surveillance group (83% vs. 77%, P = .042). CONCLUSION: Intraoperative measurements of graft flow and resistance do not predict graft outcome at six weeks. However, surveillance does identify at-risk grafts and improves mid-term primary-assisted patency.

Effect of ramipril on renal function in patients with intermittent claudication.

BACKGROUND: The Heart Outcomes Prevention Study (HOPE) demonstrated that ramipril resulted in a blood-pressure-independent 25% reduction in cardiovascular events in patients with peripheral arterial disease (PAD). Despite this, general practitioners and vascular surgeons remain reluctant to prescribe ACE inhibitors in this group of patients because of concerns about renal artery stenosis (RAS). We aimed to define the effect of ramipril on renal function in patients with intermittent claudication (IC). METHODS AND RESULTS: Of 132 unselected patients with IC entering the study 78 (59%) were excluded due to: current ACE inhibitor use (38%), renal impairment (serum creatinine above normal range) (15%), known severe RAS (1%) or unwillingness to participate (5%). The remaining 54 patients were titrated to 10 mg ramipril and renal function was monitored at 1, 5, and 12 weeks. Treatment was discontinued during titration in 5 patients due to symptoms (3) or lack of compliance (2). In the remainder, median [IQR] serum creatinine increased (94 [85.8-103.3] to 98 [88.0-106.5] micromol/L, p < or = 0.001) and median [IQR] GFR decreased (71.5 [64.6-82.3] to 68.7 [59.8-74.7] mL/min per 1.73 m2, p < or = 0.001) between baseline and 5 weeks. These changes were not considered clinically significant. By 12 weeks these values had returned almost to baseline (Cr 95.5 [88.0-103.25] micromol/L, GFR 71.8 [65.3-77.4] mL/min). No patient had a serum creatinine rise > 30%. CONCLUSION: Most of patients with IC and a normal serum creatinine can be safely commenced on ramipril provided they are screened, titrated and monitored as described above. Studies in patients with borderline renal impairment (serum creatinine up to 30% above baseline) are on-going.

Amputation for osteomyelitis in a patient with spina bifida.

We describe a case of osteomyelitis in a patient with spina bifida presenting to the vascular surgeon and highlight the complex challenges encountered. We review the literature and demonstrate how good multidisciplinary care and early consideration for surgical amputation may benefit this unique group of patients.

The role of compression after endovenous ablation of varicose veins.

OBJECTIVE: The aim of this review was to identify the evidence regarding the optimal duration of compression therapy after endovenous ablation of varicose veins. METHODS: Electronic databases were searched for studies assessing the use of compression after endovenous ablation in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The primary outcomes for this study were pain score and complications. Secondary outcomes were time to full recovery, quality of life score, leg circumference, bruising score, and compliance rates. RESULTS: Following strict inclusion and exclusion criteria, five studies were included in our review, including a total of 734 patients. The short-duration compression therapy ranged from 4 hours to 2 days, whereas the longer duration ranged from 3 to 15 days. A single study showed a better outcome in terms of complications with a short compression therapy. A single study showed a benefit to pain and quality of life with extended compression therapy, whereas the others did not. There was no significant difference in terms of bruising, recovery time, and leg swelling. CONCLUSIONS: Our review showed that there is no evidence for the extended use of compression after endovenous ablation of varicose veins.

Screening for popliteal aneurysms should not be a routine part of a community-based aneurysm screening program.

INTRODUCTION: Several studies have found an increased incidence of peripheral aneurysms in patients with an abdominal aortic aneurysm (AAA). The aim of this study was to determine whether screening for popliteal aneurysms should be part of an AAA screening programme. SETTING: A community-based AAA screening programme. METHODS: The diameters of the internal abdominal aorta and both popliteal arteries were assessed by B-Mode ultrasound in a subgroup of the screened population. An AAA was defined as an infrarenal aortic diameter > 29 mm. A popliteal aneurysm was defined as a popliteal diameter > 19 mm. RESULTS: Information was available for 283 subjects, 112 subjects with a small AAA, and 171 subjects with a normal aorta. No popliteal aneurysms were found in the subjects with a normal aorta. Three popliteal aneurysms were found in patients with a small AAA. Scanning both popliteal arteries took an experienced sonographer on average three times as long as scanning for an AAA (5 vs 15 minutes). CONCLUSION: Popliteal artery aneurysms are seen in less than 3% of men with a small AAA and not at all in men with a normal aortic diameter. It is therefore not cost effective to include screening for popliteal aneurysms in population screening for AAA.

A case of Paget-Schroetter syndrome (PSS) in a young judo tutor: a case report.

BACKGROUND: We present a case of unsuspected Paget-Schroetter syndrome (also called effort thrombosis), one of the rare causes of upper extremity deep vein thrombosis. To the best of our knowledge, this was the first such case in our hospital. Our patient may have been discharged with an incomplete diagnosis and inappropriate management but for one of the few physicians who knew about effort thrombosis, made the diagnosis, and referred the patient promptly to the appropriate team. CASE PRESENTATION: A 37-year-old Caucasian man who was an active judo tutor presented to the acute medical unit in our hospital. He had initially presented to his primary care physician complaining of redness and swelling of his right arm and elbow of 1 week's duration. He had been prescribed some antibiotics by his general practitioner, but his symptoms worsened. At that point, he was referred to our hospital for further review of his arm swelling. CONCLUSIONS: When considering a diagnosis of deep vein thrombosis, the age, hobbies, and occupation, among other things, of individual patients should be put into context at all times to avoid missing rare causes such as Paget-Schroetter syndrome. This report is intended to raise awareness of this rare condition. Knowledge of this condition and its management is essential for all medical practitioners, especially medical doctors who are involved in unselected medical admissions in accident and emergency or medical admission units, where the majority of such patients are seen.

Nonsteroidal antiinflammatory drugs are associated with increased aortic stiffness.

OBJECTIVES: Nonsteroidal antiinflammatory drugs (NSAIDS) have been shown to retard aneurysm growth in animal models. In vitro studies have shown an inhibitory effect of NSAIDS on matrix metalloproteinase-9, interleukin-1beta, and IL-6 mediated arterial wall elastolysis. The aim of this study was to investigate the effects of NSAIDs on arterial stiffness, a surrogate marker of elastolysis. METHODS: 447 subjects enrolled in a community-based abdominal aortic aneurysm (AAA) screening program were assessed for age, blood pressure, smoking status, and drug history. Aortic diameter and stiffness were measured by M-Mode ultrasound. The concentration of the amino-terminal propeptide of type III procollagen was used as a proxy measurement of type III collagen turnover. RESULTS: NSAID ingestion was significantly (p = 0.006) associated with increased aortic wall stiffness after adjusting for age, aortic diameter, blood pressure, and smoking status. No such effect was seen for beta-blockers, calcium channel antagonists, nitrates, angiotensin-converting enzyme inhibitors, diuretics, or antiplatelet agents. DISCUSSION: These novel data show that NSAIDS are associated with increased aortic stiffness, possibly through the effects of cytokine mediated elastolysis. This in turn may prevent aortic expansion and the development of AAA.

The effect of supervised exercise and cilostazol on coagulation and fibrinolysis in intermittent claudication: a randomized controlled trial.

BACKGROUND: The prothrombotic, hypofibrinolytic state that develops in patients with intermittent claudication (IC) upon walking due to ischemia-reperfusion injury (IRI) of the leg muscles may contribute to the high incidence of life- and limb-threatening thrombotic events observed in this patient group. Treatments, such as angioplasty, that obtund the IRI also ameliorate the procoagulant diathesis. The effect on this diathesis of supervised exercise and cilostazol, both of which provide symptomatic benefit in IC, but without significantly obtunding IRI, is unknown. METHODS: Thirty-four patients (27 men and 7 women; median age, 67 years; range, 63-72 years) were randomized to receive best medical therapy (BMT) plus supervised exercise (n = 9), BMT plus cilostazol (n = 9), BMT plus supervised exercise plus cilostazol (n = 7), or BMT alone (n = 9) in a 2 x 2 factorial design. Thrombin-antithrombin complex and prothrombin fragments 1 and 2, both markers of thrombin generation; plasminogen activator inhibitor antigen and tissue plasminogen activator antigen, both markers of fibrinolysis; ankle-brachial pressure index (ABPI); and initial and absolute claudication distance (ACD) were measured at baseline and then 3 and 6 months after randomization. RESULTS: At 6 months, when compared with receiving BMT only, supervised exercise and cilostazol resulted in improvements in ABPI of 18% and 13% and in ACD of 40% and 64%, respectively. The effects on ABPI and ACD of combining supervised exercise and cilostazol were additive. Supervised exercise, cilostazol, and supervised exercise combined with cilostazol had no significant effect on any of the four hemostatic markers. CONCLUSIONS: Treatment of IC by supervised exercise or cilostazol results in significant improvements in ABPI and ACD but has no demonstrable effect on the prothrombotic diathesis. This suggests that supervised exercise and cilostazol, unlike angioplasty, are unlikely to have a long-term beneficial effect on the thrombotic risks faced by these patients.