Research Letters

Lower-limb arterial disease

The simulation of limb ischemia in large laboratory animals is a complex and currently topical task in experimental medicine. Meanwhile, there is a demand for a reliable and effective model of limb ischemia for further testing of medicines to stimulate circulation and induce angiogenesis, gene medicines in particular. Aim of this study was to develop and experimentally test an effective method of simulation of hind limb ischemia.

Female Vietnamese pot-bellied pigs were chosen as biological models. The reproduction of the pathology was evaluated using the following methods: laser doppler flowmetry, laboratory test of venous blood, immunohistochemical reaction with antibodies against CD31, a specific marker of endothelial cells, Van Gieson's staining of muscles for presence of connective tissue and clinical observation to detect the presence of lameness in pigs.

Laser doppler flowmetry recorded a significant decrease in the intensity of the blood circulation and a marked decrease in temperate in the operated limb. Increased lactate and creatine kinase were registered immediately after the surgery and were absent 3 or more days later. Clinical observation demonstrated presence of walking lameness. Histological and immunohistochemical methods revealed a credible increase in connective tissue area and a reduction in the number of blood vessels in the muscles, confirming the presence of ischemia.

An effective approach to modeling limb ischemia has been developed and experimentally tested. The proposed model may be used in cardiovascular surgery and will allow further testing of new medications designed to treat ischemia of hind limbs.

Readmission to the hospital after revascularization for peripheral artery disease (PAD) is frequently reported. No consensus exists as to the exact frequency and risk factors for readmission. This review aimed to determine the incidence of and risk factors for 30-day readmission after revascularization for PAD.

PubMed/Medline (Ovid), Scopus, Web of Science, the Cochrane Library, and CINAHL were searched systematically from inception until May 20, 2018. Studies were eligible for inclusion if they included patients with diagnosed PAD undergoing revascularization and reported the readmission rate and a statistical evaluation of the association of at least one risk factor with readmission. Studies were excluded if data for other procedures could not be distinguished from revascularization. Two authors undertook study selection independently with the final inclusion decision resolved through consensus. The PRISMA and Meta-analyses of Observational Studies in Epidemiology guidelines were followed regarding data extraction and quality assessment, which was performed by two authors independently. Data were pooled using a random effects model.

The primary outcome was readmission within 30 days of revascularization. Fourteen publications reporting the outcomes of 526,008 patients were included. Reported readmission rates ranged from 10.9% to 30.0% with a mean of 16.4% (95% confidence interval [CI], 15.1%-17.9%). Meta-analyses suggested the following risk factors had a significant association with readmission: female sex (odds ratio [OR], 1.13; 95% CI, 1.05-1.21), black race (OR, 1.36; 95% CI, 1.28-1.46), dependent functional status (OR, 1.72; 95% CI, 1.43-2.06), critical limb ischemia (OR, 2.12; 95% CI, 1.72-2.62), emergency admission (OR, 1.75; 95% CI, 1.43-2.15), hypertension (OR, 1.39; 95% CI, 1.26-1.54), heart failure (OR, 1.82; 95% CI, 1.50-2.20), chronic pulmonary disease (OR, 1.19; 95% CI, 1.08-1.32), diabetes (OR, 1.47; 95% CI, 1.32-1.63), chronic kidney disease (OR, 1.93; 95% CI, 1.62-2.31), dialysis dependence (OR, 2.08; 95% CI, 1.75-2.48), smoking (OR, 0.83; 95% CI, 0.78-0.89), postoperative bleeding (OR, 1.70; 95% CI, 1.23-2.35), and postoperative sepsis (OR, 4.13; 95% CI, 2.02-8.47).

Approximately one in six patients undergoing revascularization for PAD are readmitted within 30 days of their procedure. This review identified multiple risk factors predisposing to readmission, which could potentially serve as a way to target interventions to reduce readmissions.

Patients with peripheral artery disease (PAD) are at substantial risk of cardiovascular events. There is interest in using blood markers, such as C-reactive protein (CRP), to monitor prognosis and treatment efficacy in PAD patients. The aim of this meta-analysis was to assess the association between CRP and major cardiovascular events in PAD patients.

Studies evaluating the association between CRP and major cardiovascular events (myocardial infarction, stroke, cardiac revascularisation and mortality) were identified using MEDLINE and the Cochrane library. Studies that did not include participants with PAD, measure CRP, or follow-up patients for cardiovascular events were excluded. Meta-analyses of published adjusted hazard ratios (HR) were conducted using an inverse variance-weighted random effects model, and heterogeneity was assessed with the I² index.

A total of 16 studies involving 5041 participants met the inclusion criteria for the systematic review. Eight studies were included in the meta-analyses. Summary effect estimates were reported as HR comparing higher and lower quantiles, and HR per unit increase in log_eCRP. PAD patients with higher CRP had a significantly greater risk of major cardiovascular events compared with those with lower CRP (HR 2.26, 95% CI 1.65–3.09, p < 0.001). The HR for major cardiovascular events was 1.38 (95% CI 1.16–1.63, p < 0.001) per unit increase in log_eCRP.

The present findings suggest that high circulating CRP is predictive of major cardiovascular events in PAD patients.

The association of vitamin D deficiency with cardiovascular disease is controversial. The present meta-analysis was performed to examine if circulating levels of 25-hydroxyvitamin D [25(OH)D] were lower in patients with peripheral artery disease (PAD) when compared to non-PAD controls.

A comprehensive database search was conducted in Web of science, Scopus, PubMed, EMBASE and The Cochrane Library to identify observational studies reporting 25(OH)D concentrations in PAD patients and non-PAD participants. Data extraction and study quality assessments were conducted independently. A random-effects model was used to meta-analyse extracted data and generate standardized mean differences (SMDs) in circulating 25(OH)D levels between PAD patients and non-PAD controls. Subgroup analyses were conducted focussing on patients presenting with intermittent claudication (IC) and critical limb ischaemia (CLI).

Six case-control studies assessing 6418 individuals fulfilled the inclusion criteria. Two studies were considered to be of moderate methodological quality and four were considered to be of high quality. A meta-analysis of data from 1217 PAD patients and 5201 non-PAD participants showed that circulating 25(OH)D concentrations were lower in PAD patients compared with non-PAD participants (SMD = −0.32, 95% CI: −0.58, −0.05; P = 0.02). Subgroup analyses showed that 25(OH)D levels were significantly lower among PAD patients with CLI, but not IC, when compared to non-PAD controls (SMD = −1.29, 95% CI: −1.66, −0.91; P < 0.001 and SMD = −0.01, 95% CI: −0.15, 0.13; P = 0.88, respectively).

This meta-analysis suggests that low levels of circulating 25(OH)D are associated with PAD presence, particularly in patients presenting with CLI. These data suggest the possibility that vitamin D insufficiency may contribute to the development of more advanced PAD although this remains to be confirmed.

3D-ultrasound (US) imaging systems offer many advantages such as convenience, low operative costs and multiple scanning options. Most 3D-US freehand tracking systems are not optimally adapted for the quantification of lower limb arterial stenoses because their performance depends on the scanning length, on ferro-magnetic interferences or because they require a constant line of sight with the US probe. Robotic systems represent a promising alternative since they can control and standardize the 3D-US acquisition process for large scanning distances without requiring a specific line of sight. The performance of a new prototype medical robot, in terms of positioning and inter-target accuracies (i.e., difference between measurements and ground truth values) was evaluated with a lower-limb mimicking phantom throughout the robot workspace. The teach/replay repeatability (i.e., difference between taught and replayed points) was also assessed. A mean positioning accuracy between 0.46 mm and 0.75 mm was found on all scanning zones. The mean inter-target distance accuracy varied between 0.26 mm and 0.61 mm. Teach/replay repeatability below 0.20 mm was also obtained. Additionally, a 3D reconstruction of in-vitro stenoses was performed with the robotic US scanner. The quantification error of a 80% area reduction (AR) stenosis was 3.0%, whereas it was −0.9% for a less severe 75% AR stenosis. Altogether, these results suggest that the robot may be of value for the clinical evaluation of lower limb vessels over long and tortuous segments starting from the iliac artery down to the popliteal artery below the knee.