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Matrix metalloproteinases and risk stratification in patients undergoing surgical revascularisation for critical limb ischaemia.

ABSTRACT: Critical limb ischaemia (CLI) is the most advanced form of peripheral artery disease (PAD) and it is often associated with foot gangrene, which may lead to major amputation of lower limbs, and also with a higher risk of death due to fatal cardiovascular events. Matrix metalloproteinases (MMPs) seem to be involved in atherosclerosis, PAD and CLI. Aim of this study was to evaluate variations in MMP serum levels in patients affected by CLI, before and after lower limb surgical revascularisation through prosthetic or venous bypass. A total of 29 patients (7 females and 22 males, mean age 73·4 years, range 65-83 years) suffering from CLI and submitted to lower extremity bypass (LEB) in our Institution were recruited. Seven patients (group I) underwent LEB using synthetic polytetrafluoroethylene (PTFE) graft material and 22 patients (group II) underwent LEB using autogenous veins. Moreover, 30 healthy age-sex-matched subjects were also enrolled as controls (group III). We documented significantly higher serum MMPs levels (P < 0·01) in patients with CLI (groups I and II) with respect to control group (group III). Finally, five patients with CLI (17·2%) showed poor outcomes (major amputations or death), and enzyme-linked immunosorbent assay (ELISA) test showed very high levels of MMP-1 and MMP-8. MMP serum levels seem to be able to predict the clinical outcomes of patients with CLI.

SUBMITTER: De Caridi G

PROVIDER: S-EPMC7949845 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Patients with critical limb ischemia (CLI) are a heterogeneous population with respect to risk for mortality and limb loss, complicating clinical decision-making. Endovascular options, compared with bypass, offer a tradeoff between reduced procedural risk and inferior durability. Risk stratified data predictive of amputation-free survival (AFS) may improve clinical decision making and allow for better assessment of new technology in the CLI population.This was a retrospective analysis of prospectively collected data from patients who underwent infrainguinal vein bypass surgery for CLI. Two datasets were used: the PREVENT III randomized trial (n = 1404) and a multicenter registry (n = 716) from three distinct vascular centers (two academic, one community-based). The PREVENT III cohort was randomly assigned to a derivation set (n = 953) and to a validation set (n = 451). The primary endpoint was AFS. Predictors of AFS identified on univariate screen (inclusion threshold, P < .20) were included in a stepwise selection Cox model. The resulting five significant predictors were assigned an integer score to stratify patients into three risk groups. The prediction rule was internally validated in the PREVENT III validation set and externally validated in the multicenter cohort.The estimated 1-year AFS in the derivation, internal validation, and external validation sets were 76.3%, 72.5%, and 77.0%, respectively. In the derivation set, dialysis (hazard ratio [HR] 2.81, P < .0001), tissue loss (HR 2.22, P =.0004), age >or=75 (HR 1.64, P = .001), hematocrit <or=30 (HR 1.61, P = .012), and advanced CAD (HR 1.41, P = .021) were significant predictors for AFS in the multivariable model. An integer score, derived from the ss coefficients, was used to generate three risk categories (low <or= 3 [44.4% of cohort], medium 4-7 [46.7% of cohort], high >or=8 [8.8% of cohort]). Stratification of the patients, in each dataset, according to risk category yielded three significantly different Kaplan-Meier estimates for 1-year AFS (86%, 73%, and 45% for low, medium, and high risk groups, respectively). For a given risk category, the AFS estimate was consistent between the derivation and validation sets.Among patients selected to undergo surgical bypass for infrainguinal disease, this parsimonious risk stratification model reliably identified a category of CLI patients with a >50% chance of death or major amputation at 1 year. Calculation of a "PIII risk score" may be useful for surgical decision making and for clinical trial designs in the CLI population.

Project description:BACKGROUND:Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients the disease progresses to critical limb ischaemia (CLI). In a substantial number of patients with CLI, no effective treatment option other than amputation is available and around a quarter of these patients will require a major amputation during the following year. This is an update of the review first published in 2011. OBJECTIVES:To determine the effectiveness and safety of local intramuscular transplantation of autologous adult bone marrow mononuclear cells (BMMNCs) as a treatment for critical limb ischaemia (CLI). SEARCH METHODS:For this update the Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched February 2014) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 1). SELECTION CRITERIA:We included all randomised controlled trials of CLI in which participants were randomly allocated to intramuscular administration of autologous adult BMMNCs or control (either no intervention or conventional conservative therapy). We excluded studies on patients with intermittent claudication. DATA COLLECTION AND ANALYSIS:Two authors independently selected trials, assessed trials for eligibility and methodological quality, and extracted data. Disagreements were resolved by consensus or by the third author. MAIN RESULTS:Only two small studies, with a combined total of 57 participants, met our inclusion criteria and were finally included. They were classified as having a moderate risk of bias with unclear issues regarding their methods, and according to the GRADE approach, the overall quality of the evidence would be considered as moderate. In one study the effects of intramuscular injections of BMMNCs in the ischaemic lower limbs of patients with CLI were compared with control (standard conservative treatment). No deaths were reported and no significant difference was observed between the two groups for either pain (P = 0.37) or the ankle brachial index (ABI) parameter. However, the treatment group showed a significantly smaller proportion of participants undergoing amputation compared with the control group (P = 0.026).In the other study, following subcutaneous injections of granulocyte colony-stimulating factor (G-CSF) for five days, peripheral blood derived mononuclear cells were collected and then transplanted by intramuscular injections into ischaemic lower limbs. The effects were compared with daily intravenous prostaglandin E1 injections (control group). No deaths were reported. Pain reduction was greater in the treatment group than in the control group (P < 0.001) as was increase in ABI (mean increase 0.13 versus 0.02, P < 0.01). The treatment group experienced a statistically significant increase in pain-free walking distance (PFWD) compared with the control group (mean increase 306.4 m versus 78.6 m, P = 0.007). A smaller proportion of participants underwent amputation in the treatment group compared with the control group (0% versus 36%, P = 0.007). AUTHORS' CONCLUSIONS:The data from the published trials suggest that there is insufficient evidence to support this treatment. These results were based on only two trials which had a very small number of participants. Therefore evidence from larger randomised controlled trials is needed in order to provide adequate statistical power to assess the role of intramuscular mononuclear cell implantation in patients with CLI.

Project description:BackgroundIschaemic ulcerations have been reported to persist and/or deteriorate despite technically successful revascularisations; a higher incidence of which affects patients with diabetes and critical limb ischaemia. In the context of wound healing, it is unclear if applications of the angiosome concept in 'direct revascularisation' (DR) would be able to aid the healing of chronic foot ulcerations better than the current 'best vessel' or 'indirect revascularisation' (IR) strategy in patients with co-morbid diabetes and critical limb ischaemia.MethodsA literature search was conducted in eight electronic databases, namely AMED, CINAHL, The Cochrane Library, ProQuest Health & Medicine Complete, ProQuest Nursing & Allied Health Source, PubMed, ScienceDirect and TRIP database. Articles were initially screened against a pre-established inclusion and exclusion criteria to determine eligibility and subsequently appraised using the Newcastle-Ottawa Scale.ResultsFive retrospective studies of varying methodological quality were eligible for inclusion in this review. Critical analysis of an aggregated population (n = 280) from methodologically stronger studies indicates better wound healing outcomes in subjects who had undergone DR as compared to IR (p < 0.001; p = 0.04). DR also appears to result in a nearly twofold increase in probability of wound healing within 12 months (hazard ratio, 1.97; 95% CI, 1.34-2.90). This suggests that achieving direct arterial perfusion to the site of ulceration may be important for the healing of chronic diabetic foot ulcerations.ConclusionIncorporating an angiosome-directed approach in the lower limb revascularisation strategy could be a very useful adjunct to a solely indirect approach, which could increase the likelihood of wound healing. With the limited data currently available, findings appear promising and merit from further investigation. Additional research to form a solid evidence base for this revised strategy in patients with co-morbid diabetes and critical limb ischaemia is warranted.

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Matrix metalloproteinases and risk stratification in patients undergoing surgical revascularisation for critical limb ischaemia.

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