Endovascular versus open repair of asymptomatic popliteal artery aneurysm.

BACKGROUND: Popliteal artery aneurysm (PAA) is a focal dilatation and weakening of the popliteal artery. If left untreated, the aneurysm may thrombose, rupture or the clot within the aneurysm may embolise causing severe morbidity. PAA may be treated surgically by performing a bypass from the arterial segment proximal to the aneurysm to the arterial segment below the aneurysm, which excludes the aneurysm from the circulation. It may also be treated by a stent graft that is inserted percutaneously or through a small cut in the groin. The success of the procedure is gauged by the ability of the graft to stay patent over an extended duration. While surgical treatment is usually preferred in an emergency, the evidence on first line treatment in a non-emergency setting is unclear. This is an update of a review first published in 2014. OBJECTIVES: To assess the effectiveness of an endovascular stent graft versus conventional open surgery for the treatment of asymptomatic popliteal artery aneurysms (PAA) on primary and assisted patency rates, hospital stay, length of the procedure and local complications. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 29 January 2019. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) comparing endovascular stent grafting versus conventional open surgical repair in patients undergoing unilateral or bilateral prophylactic repair of asymptomatic PAAs. DATA COLLECTION AND ANALYSIS: We collected data on primary and assisted primary patency rates (primary endpoints) as well as operating time, the length of hospital stay, limb salvage and local wound complications (secondary endpoints). We presented results as risk ratio or mean difference with 95% confidence intervals and assessed the certainty of the evidence using GRADE. MAIN RESULTS: No new studies were identified for this update. A single RCT with a total of 30 PAAs met the inclusion criteria. There was a low risk of selection bias and detection bias. However, the risks of performance bias, attrition bias and reporting bias were unclear from the study. Despite being an RCT, the certainty of the evidence was downgraded to moderate due to the small sample size, resulting in wide confidence intervals (CIs); only 30 PAAs were randomised over a period of five years (15 PAAs each in the groups receiving endovascular stent graft and undergoing conventional open surgery). The primary patency rate at one year was 93.3% in the endovascular group and 100% in the surgery group (RR 0.94, 95% CI 0.78 to 1.12; moderate-certainty evidence). The assisted patency rate at one year was similar in both groups (RR 1.00, 95% CI 0.88 to 1.13; moderate-certainty evidence). There was no clear evidence of a difference between the two groups in the primary or assisted patency rates at four years (13 grafts were patent from 15 PAA treatments in each group; RR 1.00, 95% CI 0.76 to 1.32; moderate-certainty evidence); the effects were imprecise and compatible with the benefit of either endovascular stent graft or surgery or no difference. Mean hospital stay was shorter in the endovascular group (4.3 days for the endovascular group versus 7.7 days for the surgical group; mean difference (MD) -3.40 days, 95% CI -4.42 to -2.38; P < 0.001; moderate-certainty evidence). Mean operating time was also reduced in the endovascular group (75.4 minutes in the endovascular group versus 195.3 minutes in the surgical group; MD -119.90 minutes, 95% CI -137.71 to -102.09; P < 0.001; moderate-certainty evidence). Limb salvage was 100% in both groups. Data on local wound complications were not published in the trial report. AUTHORS' CONCLUSIONS: Evidence to determine the effectiveness of endovascular stent graft versus conventional open surgery for the treatment of asymptomatic PAAs is limited to data from one small study. At one year there is moderate-certainty evidence that primary patency may be improved in the surgery group but assisted primary patency rates were similar between groups. At four years there was no clear benefit from either endovascular stent graft or surgery to primary or assisted primary patency (moderate-certainty evidence). As both operating time and hospital stay were reduced in the endovascular group (moderate-certainty evidence), it may represent a viable alternative to open repair of PAA. A large multicenter RCT may provide more information in the future. However, difficulties in recruiting enough patients are likely, unless it is an international collaboration including a number of high volume vascular centres.

Is long-term follow-up of adequately coil-occluded ruptured cerebral aneurysms always necessary? A single-center study of recurrences after endovascular treatment.

PURPOSE: Aneurysm recurrence following coil occlusion is well recognized. However, there is controversy as to how long these patients should be followed up after coiling to detect reopening. We aimed to identify the rate of late reopening and the risk factors for reopening in a large single-center cohort of ruptured aneurysms that appeared adequately occluded at 6 months. We also aimed to assess whether rates of recurrence have altered over time with improving coil and angiographic technology. METHODS: Patients treated between 1996 and 2010 were assessed and those with both 6-month initial and subsequent long-term follow-up with either digital subtraction angiography or magnetic resonance angiography were included. Aneurysms were stratified by features such as size, neck width, anatomical location and time of treatment: 1996-2005 (cohort 1) and 2006-2010 (cohort 2). ORs for risk of recurrence were calculated for aneurysm features and rates of recurrence in each cohort were compared using a χ(2) test. RESULTS: 437 patients with 458 adequately occluded aneurysms at 6 months had mean long-term follow-up of 31 months; 57 (12.4%) were large (≥ 10 mm) and 104 (22.7%) were wide-necked (>4 mm). Nine aneurysms (2%) showed significant late anatomical deterioration whereby retreatment was considered or undertaken. The risk was greater for large aneurysms (≥ 10 mm) (OR 15.61, 95% CI 3.79 to 64.33, p=0.0001) or wide-necked aneurysms (>4 mm) (OR 12.70, 95% CI 2.60 to 62.13, p=0.0017). The frequency of significant late anatomical deterioration and retreatment was also less common in those treated in cohort 2 (p<0.05). No completely occluded aneurysm at 6 months demonstrated significant late recurrence. CONCLUSIONS: Most aneurysms adequately occluded at 6 months did not show evidence of late recurrence. Large and wide-neck aneurysms are, however, at greater risk of later recurrence.

Endovascular versus open repair of asymptomatic popliteal artery aneurysm.

BACKGROUND: Popliteal artery aneurysm (PAA) is a focal dilatation and weakening of the popliteal artery. If left untreated, the aneurysm may thrombose, rupture or the clot within the aneurysm may embolise causing severe morbidity. PAA may be treated surgically by performing a bypass from the arterial segment proximal to the aneurysm to the arterial segment below the aneurysm, which excludes the aneurysm from the circulation. It may also be treated by a stent graft that is inserted percutaneously or through a small cut in the groin. The success of the procedure is gauged by the ability of the graft to stay patent over an extended duration. While surgical treatment is usually preferred in an emergency, the evidence on first line treatment in a non-emergency setting is unclear. OBJECTIVES: To assess the effectiveness of an endovascular stent graft versus conventional open surgery for the treatment of asymptomatic popliteal artery aneurysms (PAA) on primary and assisted patency rates, hospital stay, length of the procedure and local complications. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched their Specialised Register (last searched June 2014) and CENTRAL (2014, Issue 5). Clinical trials databases were searched for any ongoing or unpublished studies. SELECTION CRITERIA: All randomised controlled trials (RCTs) comparing endovascular stent grafting versus conventional open surgical repair in patients undergoing unilateral or bilateral prophylactic repair of asymptomatic PAAs were included. DATA COLLECTION AND ANALYSIS: Data were collected on primary and secondary patency rates (primary endpoints) as well as operating time, the length of hospital stay, limb salvage and local wound complications (secondary endpoints). MAIN RESULTS: A single RCT was identified that conformed to the inclusion criteria. There was a low risk of selection bias and detection bias. However, the risks of performance bias, attrition bias and reporting bias were unclear from the study. Despite being an RCT, the level of evidence was downgraded to moderate due to the small sample size, resulting in wide confidence intervals (CIs); only 30 PAAs were randomised over a period of five years (15 PAAs each in the groups receiving endovascular stent graft and undergoing conventional open surgery). The primary patency rate at one year was 100% in the surgery group and 93.3% in the endovascular group (P = 0.49). However, the assisted patency rate at one year was similar in both groups (100% patency). There was no clear evidence of a difference between the two groups in the primary or secondary patency rates at four years (13 grafts were patent from 15 PAA treatments in each group). However, the effects were imprecise and compatible with the benefit of either endovascular stent graft or surgery or no difference. Mean hospital stay was shorter in the endovascular group (4.3 days for the endovascular group versus 7.7 days for the surgical group; mean difference (MD) -3.40 days, 95% CI -4.42 to -2.38; P < 0.001). Mean operating time was also reduced in the endovascular group (75.4 minutes in the endovascular group versus 195.3 minutes in the surgical group; MD -119.20 minutes, 95% CI -137.71 to -102.09; P < 0.001). Limb salvage was 100% in both groups. Data on local wound complications were not published in the trial report. AUTHORS' CONCLUSIONS: Due to the limitations of the current evidence from one small underpowered study, we are unable to determine the effectiveness of endovascular stent graft versus conventional open surgery for the treatment of asymptomatic PAAs. A larger ongoing multicentre RCT should provide more information in the future. However, it seems reasonable to suggest that endovascular repair should be considered as a viable alternative to open repair of PAA on a case by case basis.

Potential role of erythropoietin receptors and ligands in attenuating apoptosis and inflammation in critical limb ischemia.

OBJECTIVE: Managing critical limb ischemia (CLI) is challenging. Furthermore, ischemic myopathy prevents good functional outcome after revascularization. Hence, we have focused on limiting the tissue damage rather than angiogenesis, which has traditionally been the motivation to develop nonsurgical treatments for CLI. Erythropoietin (EPO) protects ischemic tissue, and this property may also benefit CLI. The objective of this study was to examine the expression of the tissue-protective EPO receptor complex (EPOR-CD131 [ß-chain of interleukin (IL)-3/IL-5/granulocyte macrophage colony-stimulating factor receptor]) in skeletal muscle obtained from humans with CLI. Because native EPO is thrombogenic, the antiapoptotic and anti-inflammatory effects of a nonhematopoietic helix-B peptide of EPO (ARA 290) were investigated on ischemic myotubes in vitro. METHODS: Tissue was obtained from gastrocnemius muscle of 12 patients undergoing amputation for CLI and from 12 patients without limb ischemia. The expression of EPOR and CD131 was demonstrated by immunohistochemistry and Western blot. A validated in vitro model of myotube ischemia was used in which mature C2C12 myotubes were cultured 6 to 12 hours in a depleted media and gas mixture (20% CO2 and 80% N2). The myotubes were pretreated with EPO or ARA 290 before exposure to simulated ischemia. Apoptosis and cell death were determined by cleaved caspase-3 assay and lactate dehydrogenase release assay. Enzyme-linked immunosorbent assay measured the inflammatory cytokines. RESULTS: EPOR and CD131 were expressed and significantly upregulated in CLI (average optical density [OD] in Western blot [control vs CLI] EPOR, 0.05 U vs 0.1 U; CD131, 0.10 U vs 0.22 U; P < .01). There was colocalization of EPOR and CD131 in the sarcolemma (cell membrane) of the skeletal myofiber. There was no difference in the distribution of colocalization between the CLI and the normal muscle. The ischemic myotubes treated by ARA 290 in vitro had a significantly decreased number of apoptotic cells (ischemia vs ischemia plus ARA 290: 71.1% vs 55.1%; P < .01), cleaved caspase-3 (OD of ischemia vs ischemia plus ARA 290: 0.15 U vs 0.02 U; P < .01), lactate dehydrogenase release (ischemia vs ischemia plus ARA 290: 32.5 U/L vs 21.3 U/L; P < .01), and IL-6 release (OD at 450 nm, ischemia vs ischemia plus ARA 290: 0.18 vs 0.13; P < .01). CONCLUSIONS: This study demonstrates the expression and the upregulation of EPOR and CD131 in CLI and also shows that EPOR and CDI are colocalized in the cell membrane of both ischemic and control muscle fiber. The in vitro experiments demonstrate that ARA 290 decreases inflammation and apoptosis of ischemic myotubes. ARA 290 may potentially be used as adjunctive treatment for CLI.

Potential of Novel EPO Derivatives in Limb Ischemia.

Erythropoietin (EPO) has tissue-protective properties, but it increases the risk of thromboembolism by raising the haemoglobin concentration. New generation of EPO derivatives is tissue protective without the haematopoietic side effects. Preclinical studies have demonstrated their effectiveness and safety. This paper summarizes the development in EPO derivatives with emphasis on their potential use in critical limb ischaemia.

Development of an in vitro model of myotube ischemia.

Critical limb ischemia causes severe damage to the skeletal muscle. This study develops a reproducible model of myotube ischemia by simulating, in vitro, the critical parameters that occur in skeletal muscle ischemia. Monolayers of C2C12 myoblasts were differentiated into mature myotubes and exposed to nutrition depletion, hypoxia and hypercapnia for variable time periods. A range of culture media and gas mixture combinations were used to obtain an optimum ischemic environment. Nuclear staining, cleaved caspase-3 and lactate dehydrogenase (LDH) release assay were used to assess apoptosis and myotube survival. HIF-1α concentration of cell lysates, pH of conditioned media as well as partial pressures of oxygen (PO2) and carbon dioxide (PCO2) in the media were used to confirm ischemic simulation. Culturing myotubes in depleted media, in a gas mixture containing 20% CO+80% N2 for 6-12 h increased the PCO2 and decreased the pH and PO2 of culture media. This attempts to mimic the in vivo ischemic state of skeletal muscle. These conditions were used to study the potential tissue-protective effects of erythropoietin (EPO) in C2C12 myotubes exposed to ischemia. EPO (60 ng/ml) suppressed LDH release, decreased cleaved caspase-3 and reduced the number of apoptotic nuclei, suggesting significantly decreased ischemia-induced apoptosis in myotubes (P<0.01) and a potential role in tissue protection. Additional therapeutic agents designed for tissue protection can also be evaluated using this model.

Incomplete removal of great saphenous vein is the most common cause for recurrent varicose veins.

OBJECTIVE: Hie-tie and great saphenous vein (GSV) stripping decreases recurrence of varicose veins (VVs). However, varying lengths of residual-GSV are observed in patients with previous GSV stripping. This may explain high recurrence rates of VVs. The proportion of recurrent VV occurring secondary to suboptimal GSV stripping is calculated. METHODS: Patients with recurrent VV (CEAP-class > C2) underwent venous duplex-ultrasound. RESULTS: 419 limbs were investigated in 298 patients (189 women and 109 men); median age for women and men was 60 and 61 years, respectively; 32.2% had reflux in residual-GSV; 30.3% had groin-reflux; 20% had reflux in sapheno-popliteal confluence (SPC); 10.2% had primary segmental deep-venous incompetence (DVI), and 6.9% had reflux at multiple sites. The frequency of reflux in the residual-GSV was significantly greater than that of reflux in the SPC (P < .0001) and DVI (P < .0001) but not groin (P = .3652). CONCLUSION: Residual-GSV is an important cause for recurrent VV.

Review of the role of erythropoietin in critical leg ischemia.

There is a need to develop alternative treatment strategies for the 30% of patients with critical leg ischemia (CLI) for whom conventional modes of revascularization fail. The efficacy erythropoietin (EPO) in this regard has been verified in preclinical models. Erythropoietin receptors are expressed in the human skeletal muscle and possibly, upregulated in CLI. Furthermore, EPO induces angiogenesis and prevents apoptosis in the ischemic skeletal muscle. The use of EPO in conjunction with autologous bone marrow cells or gene-induced angiogenesis with vascular endothelial growth factor may be more effective in inducing angiogenesis and protecting the critically ischemic leg than EPO alone. The recently synthesized nonhemopoietic derivatives of EPO (eg, asialo erythropoietin and carbamylated erythropoietin) allow higher doses to be administered to achieve tissue protective effects, without an unwanted increase in hematocrit. This may allow translation of preclinical studies into clinical trials.

A computationally efficient approach to the estimation of two- and three-dimensional hidden Markov models.

Statistical modeling methods are becoming indispensable in today's large-scale image analysis. In this paper, we explore a computationally efficient parameter estimation algorithm for two-dimensional (2-D) and three-dimensional (3-D) hidden Markov models (HMMs) and show applications to satellite image segmentation. The proposed parameter estimation algorithm is compared with the first proposed algorithm for 2-D HMMs based on variable state Viterbi. We also propose a 3-D HMM for volume image modeling and apply it to volume image segmentation using a large number of synthetic images with ground truth. Experiments have demonstrated the computational efficiency of the proposed parameter estimation technique for 2-D HMMs and a potential of 3-D HMM as a stochastic modeling tool for volume images.

A computationally efficient evolutionary algorithm for real-parameter optimization.

Due to increasing interest in solving real-world optimization problems using evolutionary algorithms (EAs), researchers have recently developed a number of real-parameter genetic algorithms (GAs). In these studies, the main research effort is spent on developing an efficient recombination operator. Such recombination operators use probability distributions around the parent solutions to create an offspring. Some operators emphasize solutions at the center of mass of parents and some around the parents. In this paper, we propose a generic parent-centric recombination operator (PCX) and a steady-state, elite-preserving, scalable, and computationally fast population-alteration model (we call the G3 model). The performance of the G3 model with the PCX operator is investigated on three commonly used test problems and is compared with a number of evolutionary and classical optimization algorithms including other real-parameter GAs with the unimodal normal distribution crossover (UNDX) and the simplex crossover (SPX) operators, the correlated self-adaptive evolution strategy, the covariance matrix adaptation evolution strategy (CMA-ES), the differential evolution technique, and the quasi-Newton method. The proposed approach is found to consistently and reliably perform better than all other methods used in the study. A scale-up study with problem sizes up to 500 variables shows a polynomial computational complexity of the proposed approach. This extensive study clearly demonstrates the power of the proposed technique in tackling real-parameter optimization problems.