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Background Autologous bone marrow-derived stem cells have been ascribed an important therapeutic role in No-Option Critical limb Ischemia (NO-CLI). One primary endpoint for evaluating NO-CLI therapy is major amputation (AMP), which is usually combined with mortality for AMP-free survival (AFS). Only a trial which is double blinded can eliminate physician and patient bias as to the timing and reason for AMP. We examined factors influencing AMP in a prospective double-blinded pilot RCT (2:1 therapy to control) of 48 patients treated with site of service obtained bone marrow cells (BMAC) as well as a systematic review of the literature. Methods Cells were injected intramuscularly in the CLI limbs as either BMAC or placebo (peripheral blood). Six month AMP rates were compared between the two arms. Both patient and treating team were blinded of the assignment in follow-up examinations. A search of the literature identified 9 NO-CLI trials, the control arms of which were used to determine 6 month AMP rates and the influence of tissue loss. Results Fifteen amputations occurred during the 6 month period, 86.7% of these during the first 4 months. One amputation occurred in a Rutherford 4 patient. The difference in amputation rate between patients with rest pain (5.6%) and those with tissue loss (46.7%), irrespective of treatment group, was significant (p = 0.0029). In patients with tissue loss, treatment with BMAC demonstrated a lower amputation rate than placebo (39.1% vs. 71.4%, p = 0.1337). The Kaplan-Meier time to amputation was longer in the BMAC group than in the placebo group (p = 0.067). Projecting these results to a pivotal trial, a bootstrap simulation model showed significant difference in AFS between BMAC and placebo with a power of 95% for a sample size of 210 patients. Meta-analysis of the literature confirmed a difference in amputation rate between patients with tissue loss and rest pain. Conclusions BMAC shows promise in improving AMP-free survival if the trends in this pilot study are validated in a larger pivotal trial. The difference in amp rate between Rutherford 4 & 5 patients suggests that these patients should be stratified in future RCTs.

Surgical bypass of peripheral arterial occlusive disease with autologous vein grafts provides an effective means of restoring blood flow to the lower extremity, and has been a standard therapy for patients with disabling claudication or critical limb ischemia (CLI). However, failure rates may run as high as 50% within 5 years. These graft failures occur as a result of neointimal hyperplasia, a ubiquitous biologic response of blood vessel walls to injury, which is characterized by the migration and proliferation of smooth muscle cells (SMC). The E2F family of transcription factors regulates the expression of genes controlling SMC proliferation. Edifoligide (E2F Decoy) is a novel therapy that inhibits E2F function, thus attenuating neointimal hyperplasia. Its use in conjunction with a patented drug delivery pressurization chamber is under investigation. Using this system, edifoligide is administered to vein grafts in a single, ex vivo treatment following vein harvest and before implantation, resulting in minimal systemic drug exposure and excellent patient compliance. This Phase 3, randomized, double-blind, multicenter clinical trial is designed to evaluate the safety and efficacy of edifoligide in a population of approximately 1400 patients with CLI undergoing infrainguinal bypass for peripheral arterial disease (PAD). The primary outcome measure will be the time to occurrence of non-technical graft failure resulting in either graft revision or major amputation at 12 months after enrollment. A governing Clinical Events Classification committee (CEC) will adjudicate each graft failure to determine its etiology. The PREVENT III trial is the largest multicenter trial ever performed in patients receiving autologous vein bypass grafts for CLI. This landmark study will determine if edifoligide is safe and effective at preventing vein graft failure in patients undergoing lower extremity bypass, but it also provides a unique opportunity to observe current treatment practices in vascular surgery.

Whether clinically stable small abdominal aortic aneurysms should be surgically repaired or monitored with periodic noninvasive imaging is controversial. This study compared the two approaches in patients with aneurysms 4.0 to 5.4 cm in diameter. After a mean follow-up of nearly five years, there was no survival advantage associated with immediate surgical repair. This study compared the two approaches in patients with aneurysms of 4.0 to 5.4 cm. There was no survival advantage with immediate surgical repair. Each year in the United States, 9000 deaths result from rupture of abdominal aortic aneurysms. 1 Another 33,000 patients undergo elective repair of asymptomatic abdominal aortic aneurysms to prevent rupture, which results in 1400 to 2800 operative deaths. 2 , 3 Because most abdominal aortic aneurysms never rupture, 4 elective repair is undertaken only when the risk of rupture is considered high. The strongest known predictor of rupture is the maximal diameter of the aneurysm. 5 , 6 Elective repair has been recommended for patients with aneurysms of 4.0 cm or more in diameter who do not have medical contraindications, 7 although others have advocated the use . . .

Purpose: To audit the caseloads of vascular surgery residents in the management of disabling claudication and assess the influence of endovascular procedures on overall operative experience. Methods: A retrospective review was conducted of vascular surgery resident experience in the open and endovascular management of lower limb claudication during two 3-year periods (January 2000 to December 2002 and January 2003 to December 2005). The time periods differed with regard to number of surgical faculty with advanced endovascular skills (3 in the first period and 4 in the second) and the availability of portable operating room angiography equipment. Results: During the 6-year period, the operative logs of vascular surgery residents indicated participation in 283 procedures [170 (60%) open surgical interventions, including 146 suprainguinal procedures] performed for claudication. The number of procedures increased by 62% (p<0.05) from the first period (n=108) to the second (n=175). Endovascular intervention to treat aortoiliac occlusive disease increased 4-fold (14 versus 56 interventions, p=0.01) compared to a decrease in open (bypass grafting, endarterectomy) surgical repair (45 to 31 procedures, p=0.22). The greatest change in resident experience was in endovascular intervention of infrainguinal occlusive disease: the case volume increased from 4 to 39 procedures (p=0.07) during the 2 time intervals. By contrast, the number of open surgical bypass procedures was similar (45 versus 49) in each 3-year period. Conclusion: An audit of resident experience demonstrated intervention for claudication has increased during the past 6 years. The increased operative experience reflects more endovascular treatment (atherectomy, angioplasty, stent-graft placement) of femoropopliteal and aortoiliac occlusive disease, but no decrease in open surgical operative experience for claudication. This increase in endovascular intervention may be related to a decrease in the threshold for intervention.

The objective of this study was to describe the risk factors and to determine the outcomes after recurrent gastrointestinal hemorrhage after successful mesenteric arterial embolization A retrospective analysis was undertaken of a single-center experience with mesenteric arterial embolization performed for gastrointestinal hemorrhage over a 5-year period. Statistical analyses including Student's t test and Fisher's exact test were used to compare results. For the years 2001 through 2005, 36 patients (10 women; average age, 60.8 years) underwent 37 technically successful mesenteric embolizations for acute gastrointestinal hemorrhage. Two (5.4%) cases required surgical intervention for cessation of hemorrhage, and six (16.2%) patients died during their hospitalization after technically successful embolization. Nine (24.3%) patients experienced in-hospital rehemorrhage, and of these, five (55.6%) died. Risk factors for rehemorrhage included intra-abdominal malignancy (P < 0.05), transfusion requirement greater than 10 units before angiography (P < 0.05), and the source of hemorrhage other than solitary gastroduodenal artery hemorrhage (P < 0.05). The failure of initial embolization was associated with an increased incidence of death (55.6% vs 5.0%; P < 0.05) and operative intervention to cease hemorrhage (P < 0.05). The failure of technically successful mesenteric embolization is not uncommon and is associated with identifiable risk factors. Risk factor awareness should assist in patient selection for and timing of mesenteric embolization.

This study was undertaken to evaluate the efficacy of the cardiac risk stratification protocol proposed by the American College of Cardiology/American Heart Association (ACC/AHA) in predicting cardiac morbidity and mortality associated with elective, major arterial surgery. Cardiac risk stratification using ACC/AHA guidelines was done on 425 consecutive patients before 481 elective cerebrovascular (n=146), aortic/inflow (n=166), or infrainguinal (n=169) procedures at an academic Veterans Affairs Medical Center. Cardiac risk was stratified as low, intermediate, or high based on clinical risk factors, such as, Eagle criteria, history of cardiac intervention, patient functional status, results of noninvasive cardiac stress testing, and coronary angiography with coronary revascularization performed when appropriate. Outcomes (myocardial infarction, unstable angina, congestive heart failure, ventricular arrhythmia, cardiac death, and mortality) within 30 days of surgery were compared between the various risk stratification groups. Univariate and multivariate analyses were used to identify clinically useful prognostic variables from the preoperative cardiac evaluation algorithm. Overall mortality (1.7%), cardiac death (0.4%), and adverse cardiac event (4.8%) rates were low, but cardiac death and morbidity were increased (p<0.05) in high-risk stratified patients (3.4%, 11.9%) compared to intermediate (0%, 2.8%) and low (0%, 4.0%) cardiac risk groups. The presence of 3-vessel angiographic coronary artery occlusive disease was an independent predictor of cardiac morbidity, while inducible ischemia by cardiac stress imaging was not. Previous coronary revascularization was associated with increased mortality as was the development of a non-cardiac complication. Cardiac risk assessment identified 78 (18%) patients with indications for coronary angiography. Angiographic findings resulted in coronary artery intervention (9-angioplasty; 4-bypass grafting) in 13 (3%) patients who experienced no adverse cardiac events after the planned vascular surgery (15 procedures). Cardiac risk stratification using ACC/AHA guidelines can predict adverse cardiac events associated with elective vascular surgery; however, protocol modification by increased reliance on Eagle criteria and less use of cardiac stress testing can improve identification of the “highest risk” patients who may benefit from prophylactic coronary intervention.

The purpose of this study was to evaluate the effects of dichloroacetate sodium (DCA), a drug that inactivates pyruvate dehydrogenase kinase (PDH-K), on pyruvate dehydrogenase (PDH) activity, lactate level, and function of skeletal muscle in an experimental model of acute limb ischemia. Thirty-two male Sprague-Dawley rats underwent right iliac artery ligation to produce hindlimb ischemia. After 2 hours of ischemia, 16 animals received intravenous DCA (15 mg/100 g body weight) and 16 control animals received an equivalent volume of normal saline. After an additional 1 hour of ischemia (total 3 hours) tibialis anterior muscle from the ischemic limb and contralateral nonischemic limb was excised, rapidly freeze-clamped with Wallenberg tongs cooled in liquid nitrogen, and stored at -70 degrees C. Muscles specimens were subsequently assayed for PDH activity and lactate level by use of spectrophotometric techniques. An additional 16 animals (DCA-treated, n = 8; control, n = 8) underwent ex-vivo gastrocnemius muscle fatigue testing with a 10 g tension preload after 3 hours of limb ischemia. In ischemic hind limbs, DCA treatment significantly (p = 0.025) increased PDH activity (19.6 +/-1.6 micromol/min/g dry weight) compared to controls (13.1 +/-1.3 micromol/min/g dry weight). DCA treatment did not increase (p = 0.13) skeletal muscle PDH activity in the nonischemic limbs (9.6 +/-1.1 micromol/min/g dry weight, controls; 13.2 +/-1.3 micromol/min/g dry weight, DCA group). In DCA-treated animals, hind limb ischemia resulted in no significant increase in muscle lactate levels compared to the nonischemic limb, while control animals demonstrated a significant (p = 0.005) elevation in lactate level in ischemic limbs compared to contralateral nonischemic limb. Ischemia induced a significant decrease in time to muscle fatigue in both DCA-treated and control animals (p = 0.002 and 0.001, respectively). Time to muscle fatigue in DCA-treated animals was increased compared to controls (2.6 +/-0.3 versus 2 +/-0.6 minutes; p < 0.05)in ischemic limbs but was not significantly different in nonischemic limbs (DCA = 3.3 +/-0.5 minutes; control = 3.1 +/-0.6 minutes). Treatment with DCA during acute limb ischemia reduced the depression of PDH activity and lactate level of skeletal muscle. Ischemic muscle function was also improved by DCA treatment. Further investigation of the potential beneficial effects of DCA treatment on muscle injury during ischemia and reperfusion is warranted.

Multimodal (thrombolysis, surgical decompression, venous reconstruction, oral anticoagulation) treatment of primary axillary-subclavian venous thrombosis was reviewed to assess the impact of venous patency on functional outcome. Since 1996, 7 patients (6 men, 1 woman) of ages 16-53 years (mean 33 years) presented with symptomatic acute axillosubclavian venous thrombosis as a result of a recent athletic or strenuous arm activity. Five patients had undergone previous (>2 weeks) catheter-directed thrombolysis and venous angioplasty. Diagnostic contrast venography followed by repeat catheter-directed thrombolysis demonstrated abnormal (residual stenosis [n =6] or occlusion En = I1) axillosubclavian venous segments in all patients. Surgical intervention was performed at a mean interval of 7 days (range 1-19 days) after thrombolysis and consisted of thoracic outlet decompression with scalenectomy and 1st rib resection via a paraclavicular (n =4) or supraclavicular (n = 3) approach. Medial claviculectomy or cervical rib resection was performed in 2 patients. Concomitant venous surgery was performed in all patients to restore normal venous patency by circumferential venolysis (n = 7) and balloon catheter thrombectomy (n = 3), or vein-patch angioplasty (n=2), or endovenectomy (n=5), or internal jugular transposition (n=2). Postoperative venous duplex testing beyond 1 month identified recurrent thrombosis in 4 patients despite therapeutic oral anticoagulation. Subsequent venous recanalization was documented in 3 patients. Poor functional outcome was associated with an occluded venous repair and extensive venous thrombosis on initial presentation. A patent or recanalized venous repair present in 6 of 7 patients was associated with good functional outcome and may justify multimodal intervention in patients with primary axillosubclavian effort thrombosis presenting with recurrent thrombosis and significant residual disease after thrombolysis.