Applicability of Transcutaneous Oxygen Tension Measurement in the Assessment of Chronic Limb-Threatening Ischemia.

Transcutaneous oxygen tension measurement (TcPO2) is widely applied for the evaluation of chronic limb-threatening ischemia (CLTI). Nevertheless, studies that focused on the clinical value of TcPO2 have shown varying results. We identified factors that potentially play a role in TcPO2 measurement variation such as probe placement, probe temperature, and the use of a reference probe. In this review of the current literature, we assessed the application of these factors. A systematic search was conducted. Parameters that were assessed were probe placement, probe temperature, and mentioning and/or use of a reference probe. In total, 36 articles were eligible for analysis. In 24 (67%) studies, probes were placed on specific anatomical locations. Seven (19%) studies placed probes, regardless of the location of the ulcer, adjacent to an ischemic lesion or ulcer (perilesion). Selected temperature setting of the probe differed; in 18 (50%), a default probe temperature of 44°C was selected, and in 13 (36%), a different temperature was selected. In 31 (84%) studies, the use of a reference probe was not reported. Transcutaneous oxygen tension measurement is applied diversely in patients with CLTI. Homogeneity in TcPO2 protocols is warranted for reliable clinical application and to compare future TcPO2 research.

[Diabetic foot syndrome: importance of calf muscles MR spectroscopy in the assessment of limb ischemia and effect of revascularization]. / Syndrom diabetické nohy: význam MR spektroskopie lýtkových svalu pro hodnocení koncetinové ischemie a efektu revaskularizace.

AIM: The standard method for assessment of effect of revascularization in patients with diabetic foot (DF) and critical limb ischemia (CLI) is transcutaneous oxygen pressure (TcPO2). Phosphorus magnetic resonance spectroscopy (31P MRS) enables to evaluate oxidative muscle metabolism that could be impaired in patients with diabetes and its complications. The aim of our study was to compare MRS of calf muscle between patients with DF and CLI and healthy controls and to evaluate the contribution of MRS in the assessment of the effect of revascularization. METHODS: Thirty-four diabetic patients with DF and CLI treated either by autologous cell therapy (ACT; 15 patients) or percutaneous transluminal angioplasty (PTA; 12 patients) in our foot clinic during 2013-2016 and 19 healthy controls were included into the study. TcPO2 measurement was used as a standard method of non-invasive evaluation of limb ischemia. MRS examinations were performed using the whole-body 3T MR system 1 day before and 3 months after the procedure. Subjects were examined in a supine position with the coil fixed under the m. gastrocnemius. MRS parameters were obtained at rest and during the exercise period. Rest MRS parameters of oxidative muscle metabolism such as phosphocreatine (PCr), inorganic phosphate (Pi), phosphodiesters (PDE), adenosine triphosphate (ATP), dynamic MRS parameters such as recovery constant PCr (τPCr) and mitochondrial capacity (Qmax), and pH were compared between patients and healthy controls, and also before and 3 months after revascularization. RESULTS: Patients with CLI had significantly lower PCr/Pi (p < 0.001), significantly higher Pi and pH (both p < 0.01), significantly lower Qmax and prolonged τPCr (both p < 0.001) in comparison with healthy controls. We observed a significant improvement in TcPO2 at 3 months after revascularization (from 26.4 ± 11.7 to 39.7 ± 17.7 mm Hg, p < 0.005). However, the rest MRS parameters did not change significantly after revascularization. In individual cases we observed improvement of dynamic MRS parameters. There was no correlation between MRS parameters and TcPO2 values. CONCLUSION: Results of our study show impaired oxidative metabolism of calf muscles in patients with CLI in comparison with healthy controls. We observed an improvement in dynamic MRS parameters in individual cases; this finding should be verified in a large number of patients during longer follow-up.Key words: autologous cell therapy - critical limb ischemia - diabetic foot - MR spectroscopy.

Assessment of microvascular endothelial function in type 1 diabetes using laser speckle contrast imaging.

OBJECTIVE: To test whether laser speckle contrast imaging (LSCI) coupled with physiological post-occlusive reactive hyperemia (PORH) and pharmacological iontophoresis of acetylcholine (ACh) as local vasodilator stimuli could distinguish between cutaneous microvascular responses of Type 1 Diabetes (T1DM)'s patients with endothelial dysfunction and that of healthy controls. METHODS: Patients with T1DM aged ≥12years completed a clinical-epidemiological questionnaire. Data detailing patients' such as daily insulin dose, duration of diabetes, and use of pharmaceuticals such as antihypertensive drugs and statins that could interfere with endothelial function were obtained. Vascular reactivity was assessed in the forearm by LSCI and PORH at baseline and during iontophoresis of ACh using increasing anodic currents of 30, 60, 90, 120, 150 and 180µA in 10second intervals. RESULTS: This study included 50 patients with T1DM and 30 control subjects. The mean resting flux did not differ between patients and control subjects. T1DM patients exhibited endothelial dysfunction upon challenge with physiological or pharmacological stimuli. The microvascular response to both ACh and PORH (i.e., maximum response at peak and amplitude) were significantly reduced in patients with diabetes compared with control subjects (p<0.001). CONCLUSION: We demonstrated that endothelium-dependent skin microvascular vasodilator responses are significantly impaired in patients with T1DM compared to healthy subjects investigated using LSCI coupled with ACh iontophoresis and PORH. Additionally, we find that LSCI is a promising methodology for studying physiological vascular reactivity in T1DM.

Assessment of the clinical effects of cholesteryl ester transfer protein inhibition with evacetrapib in patients at high-risk for vascular outcomes: Rationale and design of the ACCELERATE trial.

BACKGROUND: Potent pharmacologic inhibition of cholesteryl ester transferase protein by the investigational agent evacetrapib increases high-density lipoprotein cholesterol by 54% to 129%, reduces low-density lipoprotein cholesterol by 14% to 36%, and enhances cellular cholesterol efflux capacity. The ACCELERATE trial examines whether the addition of evacetrapib to standard medical therapy reduces the risk of cardiovascular (CV) morbidity and mortality in patients with high-risk vascular disease. STUDY DESIGN: ACCELERATE is a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. Patients qualified for enrollment if they have experienced an acute coronary syndrome within the prior 30 to 365 days, cerebrovascular accident, or transient ischemic attack; if they have peripheral vascular disease; or they have diabetes with coronary artery disease. A total of 12,092 patients were randomized to evacetrapib 130 mg or placebo daily in addition to standard medical therapy. The primary efficacy end point is time to first event of CV death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization. Treatment will continue until 1,670 patients reached the primary end point; at least 700 patients reach the key secondary efficacy end point of CV death, myocardial infarction, and stroke, and the last patient randomized has been followed up for at least 1.5 years. CONCLUSIONS: ACCELERATE will establish whether the cholesteryl ester transfer protein inhibition by evacetrapib improves CV outcomes in patients with high-risk vascular disease.

Resting energy expenditure in patients with intermittent claudication and critical limb ischemia.

OBJECTIVE: The primary aim of this study was to compare the resting energy expenditure of patients with intermittent claudication and critical limb ischemia. A secondary aim was to identify predictors of resting energy expenditure. METHODS: One hundred patients limited by intermittent claudication and 40 patients with critical limb ischemia participated in this study. Patients were assessed on resting energy expenditure, body composition, ankle brachial index (ABI), and calf blood flow. RESULTS: Patients with critical limb ischemia had a lower resting energy expenditure than patients with intermittent claudication (1429 +/- 190 kcal/day vs 1563 +/- 229 kcal/day; P = .004), and higher body fat percentage (34.8 +/- 7.8% vs 31.5 +/- 7.8%; P = .037), higher fat mass (30.0 +/- 9.3 kg vs 26.2 +/- 8.9 kg;P = .016), and lower ABI (0.31 +/- 0.11 vs 0.79 +/- 0.23; P < .001). Resting energy expenditure was predicted by fat free mass (P < .0001), age (P < .0001), ABI (P < .0001), ethnicity (P < .0001), calf blood flow (P = .005), and diabetes (P = .008). Resting energy expenditure remained lower in the patients with critical limb ischemia after adjusting for clinical characteristics plus fat free mass (1473 +/- 27.8 kcal/day [mean +/- SEM] vs 1527 +/- 19.3 kcal/day; P = .031), but it was no longer different between groups after further adjustment for ABI and calf blood flow (1494 +/- 25.2 kcal/day vs 1505 +/- 17.7 kcal/day; P = .269). CONCLUSION: Resting energy expenditure is decreased with a progression in peripheral arterial disease (PAD) symptoms from intermittent claudication to critical limb ischemia. Furthermore, patients with critical limb ischemia who are most susceptible for decline in resting energy expenditure are older, African American patients with diabetes. The lower resting energy expenditure of patients with critical limb ischemia, combined with their sedentary lifestyle, suggests that they are at high risk for long-term positive energy balance and weight gain.

Resting energy expenditure in subjects with and without intermittent claudication.

Subjects with peripheral arterial disease and intermittent claudication have ischemia of the lower extremities, but little is known how this influences resting energy expenditure. The objective of the study was to compare the resting energy expenditure of subjects with and without intermittent claudication. One hundred six subjects limited by intermittent claudication and 77 controls who did not have peripheral arterial disease and intermittent claudication participated in this study. Subjects were assessed on resting energy expenditure, body composition, ankle/brachial index (ABI), and calf blood flow. Subjects with intermittent claudication had a lower resting energy expenditure (1585 +/- 251 vs 1716 +/- 277 kcal/d, P = .019), higher body fat percentage (33.4% +/- 10.7% vs 29.6% +/- 7.7%, P = .016), higher fat mass (29.6 +/- 10.6 vs 24.2 +/- 8.9 kg, P = .011), and lower ABI (0.66 +/- 0.20 vs 1.19 +/- 0.12, P < .001). Resting energy expenditure was predicted by fat-free mass (P < .001), ABI (P = .027), and calf blood flow (P = .040). Resting energy expenditure remained lower in the subjects with intermittent claudication after adjusting for clinical characteristics plus fat-free mass (1611 +/- 171 vs 1685 +/- 209 kcal/d, P = .035), but was no longer different between groups after further adjustment for ABI and calf blood flow (1622 +/- 165 vs 1633 +/- 185 kcal/d, P = .500). Subjects with intermittent claudication have lower resting energy expenditure than controls, which is partially explained by ABI and calf blood flow.