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Limb ischemia, acute [keywords]
- Defining utility and predicting outcome of cadaveric lower extremity bypass grafts in patients with critical limb ischemia. [JOURNAL ARTICLE]
- J Vasc Surg 2014 Jul 16.
Despite poor long-term patency, acceptable limb salvage has been reported with cryopreserved saphenous vein bypass (CVB) for various indications. However, utility of CVB in patients with critical limb ischemia (CLI) remains undefined. The purpose of this analysis was to determine the role of CVB in CLI patients and to identify predictors of successful outcomes.A retrospective review of all lower extremity bypass (LEB) procedures at a single institution was completed, and CVB in CLI patients were further analyzed. The primary end point was amputation-free survival. Secondary end points included primary patency and limb salvage. Life tables were used to estimate occurrence of end points. Cox regression analysis was used to determine predictors of limb salvage.From 2000 to 2012, 1059 patients underwent LEB for various indications, of whom 81 received CVB for either ischemic rest pain or tissue loss. Mean age (±standard deviation) was 66 ± 10 years (male, 51%; diabetes, 51%; hemodialysis dependence, 12%), and 73% (n = 59) had history of failed ipsilateral LEB or endovascular intervention. None had sufficient autogenous conduit for even composite vein bypass. Infrainguinal CVB (infrapopliteal target, 96%; n = 78) was completed for multiple indications including Rutherford class 4 (42%; n = 34), class 5 (40%; n = 32), and class 6 (18%; n = 15). Eleven (14%) had CLI and concomitant graft infection (n = 8) or acute on chronic ischemia (n = 3). Intraoperative adjuncts (eg, profundaplasty, suprainguinal stent or bypass) were completed in 49% (n = 40) of cases. Complications occurred in 36% (n = 29), with 30-day mortality of 4% (n = 3). Median follow-up for CLI patients was 11.8 (interquartile range, 0.4-28.4) months with corresponding 1- and 3-year actuarial estimated survival (±standard error mean) of 84% ± 4% and 62% ± 6%. Primary patency of CVB for CLI was 27% ± 6% and 17% ± 6% at 1 and 3 years, respectively. Amputation-free survival was 43% ± 6% and 23% ± 6% at 1 and 3 years, respectively, and significantly higher for rest pain (59% ± 9%, 36% ± 10%) compared with tissue loss (31% ± 7%, 14% ± 7%; log-rank, P = .04). Freedom from major amputation after CVB for CLI was 57% ± 6% and 43% ± 7% at 1 and 3 years. Multivariable predictors of limb salvage for the CVB CLI cohort included postoperative warfarin (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.2-0.8), dyslipidemia (HR, 0.4; 95% CI, 0.2-0.9), and rest pain (HR, 0.4; 95% CI, 0.2-0.9). Predictors of major amputation included graft infection (HR, 3.1; 95% CI, 1.1-9.0).In CLI patients with no autologous conduit and prior failed infrainguinal bypass, CVB outcomes are disappointing. CVB performs best in patients with rest pain, particularly those who can be anticoagulated with warfarin. However, it may be an acceptable option in patients with minor tissue loss or concurrent graft infection, but consideration should be weighed against the known natural history of nonrevascularized CLI and nonbiologic conduit alternatives, given potential cost implications.
- Thrombolysis of occluded femoropopliteal graft with locally delivered human plasmin. [Journal Article]
- Srp Arh Celok Lek 2014 May-Jun; 142(5-6):342-6.
Acute lower limb ischemia results from thrombosis or embolization of diseased native artery or previously implanted bypass graft. When this occurs, several options are available to restore blood flow: catheter-directed thrombolysis, mechanical thrombectomy or open surgery. Fundamental reasons to apply percutaneous interventions are avoiding open procedures in high risk patients, and avoiding difficult dissection through scar tissue.A 67-year-old male was admitted at our Institution for critical limb ischemia. After performed angiography the diagnosis of occluded femoropopliteal graft was established. Occlusion was resolved by catheter-directed thrombolysis with plasmin. Culprit lesions were treated by angioplasty.Our patient underwent a successful thrombolysis of occluded femoropopliteal graft with locally-delivered human plasmin.
- Safety, feasibility, and effect of remote ischemic conditioning in patients undergoing lung transplantation. [JOURNAL ARTICLE]
- J Heart Lung Transplant 2014 May 9.
Primary graft dysfunction (PGD) remains a significant problem after lung transplantation. Data from animal and clinical studies suggest that remote ischemic conditioning (RIC) may reduce ischemia-reperfusion injury in solid organ transplantation.A pilot randomized controlled trial of 60 patients undergoing bilateral sequential lung transplantation assessed the utility of RIC in attenuating PGD. Treated recipients underwent 3 cycles of lower limb ischemic conditioning before allograft reperfusion. The primary outcome measure was a comparison of the partial pressure of arterial oxygen/fraction of inspired oxygen ratio (P/F ratio) between treatment groups.No adverse effects of tourniquet application were observed. The mean lowest P/F ratio during the first 24 hours after transplantation was 271.3 mm Hg in the treatment arm vs 256.1 mm Hg in the control arm (p = 0.46). PGD grade and severity and the rate of acute rejection also showed a tendency to favor the treatment arm. Sub-group analysis demonstrated a significant benefit of treatment in patients with a primary diagnosis of restrictive lung disease, a group at high risk for the development of PGD. RIC was not accompanied by systemic release of high-molecular-weight group box 1. Levels of cytokines, high-molecular-weight group box 1, and endogenous secretory receptor for advanced glycation end products peaked within 2 hours after reperfusion and likely reflected donor organ quality rather than an effect of RIC.RIC did not significantly improve P/F ratios or PGD in this randomized controlled trial. However, encouraging results in this small study warrant a large multicenter trial of RIC in lung transplantation.
- The CD133(+) Cell as Advanced Medicinal Product for Myocardial and Limb Ischemia. [JOURNAL ARTICLE]
- Stem Cells Dev 2014 Aug 20.
Ischemic diseases are the major cause of death and morbidity in Western countries. In the last decade, cell therapy has been suggested to be a promising treatment both in acute/chronic myocardial and peripheral ischemia. Different cell lineages have been tested, including endothelial progenitor cells. A subpopulation of bone marrow-derived immature ECPs, expressing the highly conserved stem cell glycoprotein antigen prominin-1 or CD133 marker, was shown to possess pro-angiogenic and antiapoptotic effects on ischemic tissues. The mechanisms implicated in CD133(+) cells ability to contribute to neovascularization processes have been attributed to their ability to directly differentiate into newly forming vessels and to indirectly activate pro-angiogenic signaling by paracrine mechanisms. A large body of in vivo experimental evidences has demonstrated the potential of CD133(+) cells to reverse ischemia. Moreover, several clinical trials have reported promising beneficial effects after infusion of autologous CD133(+) into ischemic heart and limbs exploiting various delivery strategies. These trials have contributed to characterize the CD133(+) manufacturing process as an advanced cell product (AMP). The aim of this review is to summarize available experimental and clinical data on CD133(+) cells in the context of myocardial and peripheral ischemia, and to focus on the development of the CD133(+) cell as an anti-ischemic AMP.
- Vasospastic limb ischemia presenting acute and chronic limb ischemia. [Journal Article]
- Ann Vasc Dis 2014; 7(2):169-72.
Vasospastic limb ischemia might have been underappreciated compared to vasospasm in other territories such as heart and brain. However, an increasing awareness of this vascular disorder can be translated to an improved patients' care. Herein, we report a case of vasospasm presenting acute and chronic limb ischemia in four extremities.
- Hybrid revascularization for critical limb ischemia triggered by multiple organ dysfunction due to acute pneumonia; urgent catheter intervention followed by low-density-lipoprotein apheresis and elective peripheral bypass surgery. [Journal Article]
- Ann Vasc Dis 2014; 7(2):159-64.
A 66-year-old man was referred for treatment of critical limb ischemia arising with multiple organ dysfunction due to acute pneumonia. Angiographic examinations demonstrated total obstruction of the bilateral external iliac arteries and the bilateral superficial femoral arteries with collateral circulation to the distal vessels. Urgent percutaneous transluminal angioplasty dissolved the obstruction of the left external iliac artery, and subsequent low-density-lipoprotein apheresis ameliorated his progressive ischemia in the lower extremities. Femoro-femoral and bilateral femoro-popliteal bypasses were performed 31 days after the endovascular intervention, which achieved successful limb salvage with the relief of ischemic symptoms related to arteriosclerotic obliterans.
- Novel adjunctive treatments of myocardial infarction. [Journal Article, Review]
- World J Cardiol 2014 Jun 26; 6(6):434-43.
Myocardial infarction is a major cause of death and disability worldwide and myocardial infarct size is a major determinant of prognosis. Early and successful restoration of myocardial reperfusion following an ischemic event is the most effective strategy to reduce final infarct size and improve clinical outcome, but reperfusion may induce further myocardial damage itself. Development of adjunctive therapies to limit myocardial reperfusion injury beyond opening of the coronary artery gains increasing attention. A vast number of experimental studies have shown cardioprotective effects of ischemic and pharmacological conditioning, but despite decades of research, the translation into clinical effects has been challenging. Recently published clinical studies, however, prompt optimism as novel techniques allow for improved clinical applicability. Cyclosporine A, the GLP-1 analogue exenatide and rapid cooling by endovascular infusion of cold saline all reduce infarct size and may confer clinical benefit for patients admitted with acute myocardial infarcts. Equally promising, three follow-up studies of the effect of remote ischemic conditioning (RIC) show clinical prognostic benefit in patients undergoing coronary surgery and percutaneous coronary intervention. The discovery that RIC can be performed noninvasively using a blood pressure cuff on the upper arm to induce brief episodes of limb ischemia and reperfusion has facilitated the translation of RIC into the clinical arena. This review focus on novel advances in adjunctive therapies in relation to acute and elective coronary procedures.
- Outcome and complications after intra-arterial thrombolysis for lower limb ischaemia with or without continuous heparin infusion. [JOURNAL ARTICLE]
- Br J Surg 2014 Jun 25.
Thrombolysis is a common treatment for acute leg ischaemia. The purpose of this study was to evaluate different thrombolytic treatment strategies, and risk factors for complications.This was a retrospective analysis of prospective databases from two vascular centres. One centre used a higher dose of heparin and recombinant tissue plasminogen activator (rtPA).Some 749 procedures in 644 patients of median age 73 years were studied; 353 (47·1 per cent) of the procedures were done in women. The aetiology of ischaemia was graft occlusion in 38·8 per cent, acute arterial thrombosis in 32·2 per cent, embolus in 22·3 per cent and popliteal aneurysm in 6·7 per cent. Concomitant heparin infusion was used in 63·2 per cent. The mean dose of rtPA administered was 21·0 mg, with a mean duration of 25·2 h. Technical success was achieved in 80·2 per cent. Major amputation and death within 30 days occurred in 13·1 and 4·4 per cent respectively. Bleeding complications occurred in 227 treatments (30·3 per cent). Blood transfusion was needed in 104 (13·9 per cent). Three patients (0·4 per cent of procedures) had intracranial bleeding; all were fatal. Amputation-free survival was 83·6 per cent at 30 days at both centres. In multivariable analysis, preoperative severe ischaemia with motor deficit was the only independent risk factor for major bleeding (odds ratio (OR) 2·98; P < 0·001). Independent risk factors for fasciotomy were severe ischaemia (OR 2·94) and centre (OR 6·50). Embolic occlusion was protective for major amputation at less than 30 days (OR 0·30; P = 0·003). Independent risk factors for death within 30 days were cerebrovascular disease (OR 3·82) and renal insufficiency (OR 3·86).Both treatment strategies were successful in achieving revascularization with acceptable complication rates. Continuous heparin infusion during intra-arterial thrombolysis appeared to offer no advantage.
- Remote Ischemic Preconditioning for Prevention of Acute Kidney Injury: A Meta-analysis of Randomized Controlled Trials. [JOURNAL ARTICLE]
- Am J Kidney Dis 2014 Jun 20.
Remote ischemic preconditioning (RIPC) to prevent acute kidney injury (AKI) following cardiac and vascular interventions is a controversial practice.We conducted a systematic review and meta-analysis using the MEDLINE database (1966 through November 2013), EMBASE (1988 through November 2013), and Cochrane Library database.Patients undergoing cardiac and vascular interventions.Randomized controlled trials comparing patient outcome with or without RIPC for prevention of AKI following cardiac and vascular interventions.RIPC using an inflatable tourniquet around the limb or cross-clamping the iliac arteries versus non-RIPC.AKI, need for renal replacement therapy, postoperative kidney biomarkers, in-hospital mortality, and length of intensive care unit and hospital stay.13 trials (1,334 participants) were included. RIPC decreased the risk of AKI for patients undergoing cardiac and vascular interventions compared with the control group (11 trials; 1,216 participants; risk ratio [RR], 0.70; 95%CI, 0.48-1.02; P=0.06; I(2)=45%) with marginal statistical significance. There were no differences in levels of postoperative kidney biomarkers (serum creatinine and glomerular filtration rate), incidence of renal replacement therapy, in-hospital mortality, hospital stay, or intensive care unit stay between the 2 groups. Metaregression analysis indicated that contrast intervention was not a covariate contributing significantly to heterogeneity on the risk estimate for AKI incidence; also, there was no dose effect of RIPC using tourniquet cuff around the limb on AKI prevention based on different ischemia duration.Different AKI definitions adopted in the trials included.RIPC might be beneficial for the prevention of AKI following cardiac and vascular interventions, but the current evidence is not robust enough to make a recommendation. Adequately powered trials are needed to provide more evidence in the future.
- Remote ischemic preconditioning as prevention of transfusion-related acute lung injury. [JOURNAL ARTICLE]
- Med Hypotheses 2014 Jun 7.
Transfusion-related acute lung injury (TRALI) is a serious complication of transfusion medicine, considered now as the leading cause of transfusion-related mortality. It may occur in up to 1 in 5000 transfusions and carries an elevated morbidity and mortality. Clinically it presents as hypoxia and non-cardiogenic pulmonary edema, usually within 6h of transfusion. It consists of an immunological phenomenon involving the activation of neutrophils and endothelial injury, leading to capillary leak and pulmonary edema, mechanisms shared with lung ischemia-reperfusion (IR) injury. Brief and repetitive periods of ischemia in an organ or limb have been shown to protect against subsequent major IR injury in distant organs, a phenomenon called remote ischemic preconditioning (RIPC). Limb RIP has been shown to protect the lung against IR injury trough modulation of endothelial function as well as neutrophil activation and infiltration. The protective effects of RIPC on the lung have been confirmed in clinical trials of orthopedic and cardiothoracic surgery. RIPC is a safe, tolerable and cheap procedure. I propose that limb RIPC could be used as a preventive strategy against the development of TRALI.