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.

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.

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.

The role of tissue factor in patients undergoing open repair of ruptured and nonruptured abdominal aortic aneurysms.

BACKGROUND: Ruptured abdominal aortic aneurysm (AAA) is associated with the development of a procoagulant and hypofibrinolytic state. Tissue factor (TF) and its naturally occurring inhibitor, tissue factor pathway inhibitor (TFPI), play a central role in the initiation and progression of such a hypercoagulable state, but their role in patients undergoing open AAA repair has not previously been examined. METHODS: A prospective study was conducted of 17 patients undergoing elective AAA repair and 10 patients undergoing emergency AAA repair. Blood was taken before induction, and 5 minutes, 24 hours, and 48 hours after aortic cross-clamp release and assayed for plasma TF, TFPI, tissue plasminogen activator (t-PA), plasminogen activator inhibitor (PAI), and thrombin-activatable fibrinolysis inhibitor (TAFI) activities. RESULTS: TF activity was significantly higher at all time points in patients with ruptured AAA compared with nonruptured AAA. The median (interquartile range, IRQ) TF activity (AU/mL) was 9.9 vs 3.2 (IRQ, 5.9 to 12.6 vs 2.0 to 7.6; P = .005) at preinduction; 10.7 vs 1.5 (IRQ, 9.2 to 18.3 vs 0.1 to 6.6; P = .003) at 5 minutes after clamp release; 9.5 vs 3.3 (IRQ, 7.0 to 13.5 vs 1.0 to 7.9; P = .013) at 24 hours, and 9.6 vs 3.9 (IRQ, 7.6 to 12.6 vs 2.4 to 8.7; P = .006) at 48 hours. TFPI levels were not significantly different between ruptured AAA and nonruptured AAA before or during operation but became significantly elevated at 24 and 48 hours in patients who had undergone repair of ruptured AAA. Ruptured AAA repair was associated with a hypofibrinolytic state compared with nonruptured AAA. CONCLUSIONS: The present study has demonstrated for the first time, to our knowledge, that ruptured AAA is associated with significantly higher perioperative levels of circulating TF compared with nonruptured AAA. Furthermore, in the immediate perioperative period, the high levels of TF are not associated with a corresponding rise in TFPI levels, indicating an unopposed prothrombotic state. Direct inhibition of TF by administration of anti-TF antibodies or recombinant TFPI remains to be evaluated in subjects presenting with hemorrhage due to ruptured AAA, but if given early enough, it may attenuate the early deleterious effects of unopposed TF expression and ultimately contribute to improved outcomes.

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.

The constitutive procoagulant and hypofibrinolytic state in patients with intermittent claudication due to infrainguinal disease significantly improves with percutaneous transluminal balloon angioplasty.

BACKGROUND: Patients with intermittent lower limb claudication (IC) exhibit a prothrombotic diathesis that is acutely exacerbated by exercise. This may occur because of ischemia/reperfusion injury within the leg muscles during walking and may contribute to the increased risk of thrombotic vascular events in this group of patients. This randomized study compared the effect of lower limb revascularization by percutaneous transluminal balloon angioplasty (PTA), supervised exercise, and best medical therapy (BMT) alone on this prothrombotic state. METHODS: Twenty-three patients (16 men and 7 women; median age, 67 years; range, 57-77 years) with IC due to infrainguinal disease were randomized to receive BMT alone (n = 7), BMT plus PTA (n = 9), or BMT plus supervised exercise (n = 7) as part of the Health Technology Assessment-funded EXercise vs Angioplasty in Claudication Trial (EXACT). Patients were assessed at baseline and at 3 and 6 months. Thrombin-antithrombin complex (TAT) was determined as a marker of thrombin generation, and plasminogen activator inhibitor (PAI) antigen was determined as a marker of fibrinolysis. Increased TAT indicates a procoagulant state, and increased PAI antigen indicates a hypofibrinolytic state. RESULTS: At 6 months, subjects randomized to BMT plus PTA demonstrated a significant improvement in ankle-brachial pressure index (P = .013) and maximal walking distance (P = .008), a significant decline in resting thrombin generation (median [interquartile range] TAT, 6.4 microg/L [2.7-13.5 microg/L] to 1.5 microg/L [0.3-2.9 microg/L]; P = .038), and an improvement in resting fibrinolysis (median [interquartile range] PAI-1, 10.0 ng/mL [1.0-20.5 ng/mL] to 1.0 ng/mL [1.0-14.8 ng/mL]; P = .043). There was no significant change in any of these parameters in patients randomized to BMT plus supervised exercise or to BMT alone. CONCLUSIONS: The addition of lower limb revascularization by PTA to BMT in patients with IC due to infra-inguinal disease results in a medium-term improvement in the resting procoagulant and hypofibrinolytic state. This may translate into a reduction in morbidity and mortality from thrombotic vascular events in this group of patients.

Assessment of smoking status in patients with peripheral arterial disease.

OBJECTIVE: To assess the utility of a novel rapid urinary cotinine assay to detect and quantify the level of smoking in patients with peripheral arterial disease. METHODS: This was a cross-sectional study in a vascular surgical outpatient department of a large teaching hospital. Participants were 100 consecutive subjects presenting to a hospital outpatient clinic with a diagnosis of intermittent claudication confirmed by a positive Edinburgh claudication questionnaire and an ankle-brachial pressure index of less than 0.9. Main outcome measures were patient-offered smoking history, exhaled breath carbon monoxide levels, urinary cotinine levels as measured by a novel rapid assay, and laboratory-measured creatinine-adjusted urinary cotinine levels. Results Fifty-five subjects declared that they were current smokers, 40 declared that they were ex-smokers, and 5 declared that they were never-smokers. Of the 40 ex-smokers, 6 subjects (15%) had urinary cotinine levels greater than 500 ng/mL (regular smokers), and a further 2 (5%) had urinary cotinine levels between 100 and 500 ng/mL (light, irregular, or passive smokers). The rapid urinary cotinine assay had a sensitivity and specificity of 100% and 98%, respectively, in its ability to detect active smoking, and the degree of smoking correlated well with laboratory creatinine-corrected urinary cotinine levels (Spearman coefficient, 0.805; P < .001). By contrast, exhaled carbon monoxide had a sensitivity and specificity of 95% and 89%, respectively, and although it correlated well with urinary cotinine (Spearman coefficient, 0.782; P < .001), it was found on linear regression analysis to be unreliable in differentiating light smokers from nonsmokers. CONCLUSIONS: Patient-offered smoking history is unreliable because there is no correlation between the patient-reported number of cigarettes smoked per day and urinary cotinine levels. The novel rapid assay for urinary cotinine described here is superior to exhaled carbon monoxide measurement in detecting the level of smoking exposure among patients with intermittent claudication, and its results correlate well with laboratory-measured cotinine.

The prevalence of hyperhomocysteinemia, methylene tetrahydrofolate reductase C677T mutation, and vitamin B12 and folate deficiency in patients with chronic venous insufficiency.

INTRODUCTION: Hyperhomocysteinemia (HHcy) is a risk factor for venous thromboembolism, which in turn is a major cause of chronic venous insufficiency. HHcy may be more common in patients with chronic venous insufficiency, but the cause is unknown. METHODS: One hundred hospital outpatients (52 women; median age, 66.5 years [interquartile range, 53-77 years] with venous disease C(2-6) underwent assessment of serum vitamin B(12) and folate concentration, plasma Hcy concentration, and C677T methylene tetrahydrofolate reductase (MTHR) homozygosity with polymerase chain reaction. HHcy was defined as greater than 15 micromol/L, the 95th centile of the normal range. RESULTS: CEAP classification was C(2) in 39 patients, C(3) in 10 patients, C(4) in 13 patients, C(5) in 15 patients, and C(6) in 23 patients, with median Hcy concentration 11.6, 11.5, 12.5, 15.1, and 18.1 micromol/L, respectively (Kruskall-Wallis test, P <.001). Overall prevalence of HHcy was 39% (P <.001, binomial test vs normal population), and was significantly related (Pearson chi(2) for trend, 13.616; P <.009) to clinical grade: C(2), 23%; C(3), 20%; C(4), 39%; C(5), 53%; C(6), 65%. In a linear regression model, C(6) disease was a strong independent predictor (R(2) = 20.1%) for Hcy. Overall, 5 of 49 patients (10%, NS compared with normal population [5%]) with C(2-3) disease and 10 of 51 patients (20%) (P <.001, binomial test) with C(4-6) disease were homozygous for the C677T MTHFR polymorphism. Hcy levels and prevalence of HHcy were negatively correlated with vitamin B(12) levels (r = -0.248, P =.021, and r = -0.225;, P =.037, respectively). There was no significant relationship with folate. HHcy was present in 3 patients (all with C(5-6) disease) with either vitamin B(12) or folate deficiency, and in 8 of 15 patients homozygous for MTHFR C677T. No patient had HHcy, vitamin deficiency, and C677T mutation. CONCLUSION: HHcy is common in patients with chronic venous insufficiency, especially those with ulceration. However, inasmuch as fewer than a third of patients with HHcy were C677T MTHFR homozygous or had vitamin B(12) or folate deficiency, other mechanisms must be responsible in the majority. Further work is required to determine the cause of HHcy in chronic venous insufficiency, whether HHcy is causally related to development and progression of the disease, and whether treatment would be beneficial.