Robbert Meerwaldt

Skin Autofluorescence, a Measure of Cumulative Metabolic Stress and Advanced Glycation End Products, Predicts Mortality in Hemodialysis Patients

Tissue advanced glycation end products (AGE) are a measure of cumulative metabolic stress and trigger cytokines driven inflammatory reactions. AGE are thought to contribute to the chronic complications of diabetes and ESRD. Tissue autofluorescence is related to the accumulation of AGE. Therefore, skin autofluorescence (AF) may provide prognostic information on mortality in hemodialysis (HD) patients. Skin AF was measured noninvasively with an AF reader at baseline in 109 HD patients. Overall and cardiovascular mortality was monitored prospectively during a period of 3 yr. The AF reader was validated against AGE contents in skin biopsies from 29 dialysis patients. Forty-two of the 109 (38.5%) HD patients died. Cox regression analysis showed that AF was an independent predictor of overall and cardiovascular mortality (for overall mortality odds ratio [OR] 3.9), as were pre-existing cardiovascular disease (CVD; OR 3.1), C-reactive protein (OR 1.1), and serum albumin (OR 0.3). Multivariate analysis revealed that 65% of the variance in AF could be attributed to the independent effects of age, dialysis and renal failure duration, presence of diabetes, triglycerides levels, and C-reactive protein. AF was also independently linked to the presence of CVD at baseline (OR 8.8; P < 0.001). AF correlated with collagen-linked fluorescence (r = 0.71, P < 0.001), pentosidine (r = 0.75, P < 0.001), and carboxy(m)ethyllysine (both r = 0.45, P < 0.01). Skin AF is a strong and independent predictor of mortality in ESRD. This supports a role for AGE as a contributor to mortality and CVD and warrants interventions specifically aimed at AGE accumulation.

Simple Noninvasive Measurement of Skin Autofluorescence

Abstract: Accumulation of advanced glycation end products (AGEs) is thought to play a role in the pathogenesis of chronic complications of diabetes mellitus and renal failure. Several studies indicate that AGE accumulation in tissue may reflect the cumulative effect of hyperglycemia and oxidative stress over many years. Simple quantitation of AGE accumulation in tissue could provide a tool for assessing the risk of long‐term complications. Because several AGEs exhibit autofluorescence, we developed a noninvasive autofluorescence reader (AFR). Skin autofluorescence measured with the AFR correlates with collagen‐linked fluorescence and specific skin AGE levels from skin biopsy samples. Furthermore, skin autofluorescence correlates with long‐term glycemic control and renal function, and preliminary results show correlations with the presence of long‐term complications in diabetes. The AFR may be useful as a clinical tool for rapid assessment of risk for AGE‐related long‐term complications in diabetes and in other conditions associated with AGE accumulation.

Accuracy of FDG-PET–CT in the Diagnostic Work-up of Vascular Prosthetic Graft Infection

OBJECTIVES To investigate the diagnostic accuracy of fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) compared with computed tomography (CT) scanning and added value of fused FDG-PET-CT in diagnosing vascular prosthetic graft infection. DESIGN Prospective cohort study with retrospective analysis. MATERIALS Twenty five patients with clinically suspected vascular prosthetic infection underwent CT and FDG-PET scanning. METHODS Two nuclear medicine physicians assessed the FDG-PET scans; all CT scans were assessed by two radiologists. Fused FDG-PET/CT were judged by the radiologist and the nuclear medicine physician. The concordance between CT and FDG-PET and the inter-observer agreement between the different readers were investigated. RESULTS Fifteen patients had a proven infection by culture. Single FDG-PET had the best results (sensitivity 93%, specificity 70%, positive predictive value 82% and negative predictive value 88%). For CT, these values were 56%, 57%, 60% and 58%, respectively. Fused CT and FDG-PET imaging also showed high sensitivity and specificity rates and high positive and negative values. Inter-observer agreement for FDG-PET analysis was excellent (kappa = 1.00) and moderate for CT and fused FDG-PET-CT analysis (0.63 and 0.66, respectively). CONCLUSION FDG-PET scanning showed a better diagnostic accuracy than CT for the detection of vascular prosthetic infection. This study suggests that FDG-PET provides a useful tool in the work-up for diagnosis of vascular prosthetic graft infection.

Conservative treatment of vascular prosthetic graft infection is associated with high mortality

BACKGROUND The aim of this study was to identify patient-related and/or disease-related factors that influence outcomes in patients with vascular prosthetic graft infections. METHODS Through the hospital patient administration system, between January 1997 and December 2007, a total of 44 patients were diagnosed with central prosthetic graft infections. Univariate and multivariate analyses were performed to define factors predictive of mortality. RESULTS Thirty-three men and 11 women (mean age, 71 years) were included. There was considerable comorbidity. Coagulase-negative Staphylococcus and S aureus were isolated in almost 50% of the patients. The mean follow-up duration was 5 years, during which 20 patients (46%) died. The main causes of death were related to vascular disease. Conservative treatment with antibiotics was the only variable with significant predictive value on multivariate analysis (hazard ratio, 3.62; 95% confidence interval, 1.17-11.24; P = .02). CONCLUSIONS Conservative treatment of prosthetic graft infections was associated with high mortality; therefore, it should be limited to a specific group. Patients who are not capable of undergoing open repair may benefit from conservative management. Otherwise, aggressive open treatment seems indicated.

Accumulation of Advanced Glycation End Products and Chronic Complications in ESRD Treated by Dialysis

Cardiovascular and connective tissue disorders are very common in patients with end-stage renal disease (ESRD), and the accumulation of advanced glycation end products (AGEs) is significantly increased in these patients. Accumulation of AGEs is believed to have a role in tissue protein aging and the pathogenesis of such age-related diseases as diabetes and ESRD. AGEs accumulate in patients with ESRD as a result of nonenzymatic glycation, oxidative stress, and diminished clearance of AGE precursors. Some AGEs show characteristic brown pigmentation and fluorescence, form protein-protein cross-links, and may ligate with AGE-specific receptors, inducing oxidative stress and cytokine production. This review focuses on the clinical relevance of AGE accumulation in patients with ESRD treated by dialysis for the development of long-term complications. The formation and accumulation of AGEs in patients with ESRD are discussed, as well as the relationship between AGE accumulation and such major complications of ESRD as cardiovascular and connective tissue disorders.

The Ongoing Battle Between Infrapopliteal Angioplasty and Bypass Surgery for Critical Limb Ischemia

BACKGROUND Critical limb ischemia (CLI) represents the extreme of the peripheral arterial occlusive disease spectrum and is associated with high mortality. Limb salvage often requires infrapopliteal revascularization by either angioplasty or bypass surgery. The past decade has witnessed a paradigm shift in CLI management toward endovascular treatment. This narrative review describes the clinical outcome, treatment strategy, and limitations of both modalities. METHOD A literature search was performed of the PubMed and Cochrane databases. All articles, published until September 2011, describing treatment by infrapopliteal arterial revascularization were included. RESULTS Angioplasty and bypass surgery are both related to a limb salvage rate of approximately 80% at 3-year follow-up. Patency rates appear to be higher after surgery. A reliable comparison of the two modalities, however, is complicated by various confounders, including patient selection, lesion characteristics, and complication rates. Additionally, most studies did not describe the standard use of best medical treatment or outcome for relief of ischemic pain, wound healing, or functional improvement. CONCLUSION Infrapopliteal angioplasty and bypass surgery both provide an acceptable limb salvage rate, but patency appears to be better after bypass surgery. Both modalities are likely to be complementary. Additional randomized trials are indicated to provide a treatment algorithm for patients with CLI and infrapopliteal arterial occlusive disease.

Dutch experience with the fenestrated Anaconda endograft for short-neck infrarenal and juxtarenal abdominal aortic aneurysm repair

OBJECTIVE In the past decennium, the management of short-neck infrarenal and juxtarenal aortic aneurysms with fenestrated endovascular aneurysm repair (FEVAR) has been shown to be successful, with good early and midterm results. Recently, a new fenestrated device, the fenestrated Anaconda (Vascutek, Renfrewshire, Scotland), was introduced. The aim of this study was to present the current Dutch experience with this device. METHODS A prospectively held database of patients treated with the fenestrated Anaconda endograft was analyzed. Decision to treat was based on current international guidelines. Indications for FEVAR included an abdominal aortic aneurysm (AAA) with unsuitable neck anatomy for EVAR. Planning was performed on computed tomography angiography images using a three-dimensional workstation. RESULTS Between May 2011 and September 2013, 25 patients were treated in eight institutions for juxtarenal (n = 23) and short-neck AAA (n = 2). Median AAA size was 61 mm (59-68.5 mm). All procedures except one were performed with bifurcated devices. A total of 56 fenestrations were incorporated, and 53 (94.6%) were successfully cannulated and stented. One patient died of bowel ischemia caused by occlusion of the superior mesenteric artery. On completion angiography, three type I endoleaks and seven type II endoleaks were observed. At 1 month of follow-up, all endoleaks had spontaneously resolved. Median follow-up was 11 months (range, 1-29 months). There were no aneurysm ruptures or aneurysm-related deaths and no reinterventions to date. Primary patency at 1 month of cannulated and stented target vessels was 96%. CONCLUSIONS Initial and short-term results of FEVAR using the fenestrated Anaconda endograft are promising, with acceptable technical success and short-term complication rates. Growing experience and long-term results are needed to support these findings.

Spectroscopy to improve identification of vulnerable plaques in cardiovascular disease

Many apparent healthy persons die from cardiovascular disease, despite major advances in prevention and treatment of cardiovascular disease. Traditional cardiovascular risk factors are able to predict cardiovascular events in the long run, but fail to assess current disease activity or nearby cardiovascular events. There is a clear relation between the occurrence of cardiovascular events and the presence of so-called vulnerable plaques. These vulnerable plaques are characterized by active inflammation, a thin cap and a large lipid pool. Spectroscopy is an optical imaging technique which depicts the interaction between light and tissues, and thereby shows the biochemical composition of tissues. In recent years, impressive advances have been made in spectroscopy technology and intravascular spectroscopy is able to assess the composition of plaques of interest and thereby to identify and actually quantify plaque vulnerability. This review summarizes the current evidence for spectroscopy as a measure of plaque vulnerability and discusses the potential role of intravascular spectroscopic imaging techniques.

Prospective Randomized Study of Carotid Endarterectomy with Fluoropassiv™ Thin Wall Carotid Patch versus Venous Patch

INTRODUCTION The practice of carotid endarterectomy (CEA) with patch angioplasty is more effective compared to primary closure. However, the type of patch material remains a controversy. The Fluoropassiv thin wall carotid patch is a polyester patch with an interpenetrating, nanometer-scale, solvent-applied surface modification, based on a biocompatible fluoropolymer. The present pilot study is the first clinical trial evaluating results of CEA with Fluoropassiv versus venous patch. MATERIALS/METHODS Eighty-seven patients were randomized to 42 Fluoropassiv patching and 45 venous patching. Patients were observed by a vascular surgeon and a neurologist and scanned using duplex ultrasound with a follow-up of 2 years. No patients were lost to follow-up. Restenosis was defined as a Peak Systolic Velocity ratio >2.6, lumen reduction >50%. RESULTS Perioperative stroke rate was 2.4% in the Fluoropassiv group and 8.9% in the venous group (p=0.02; 1 regressive, 4 non-regressive strokes). Multivariate analysis showed that bilateral carotid stenosis and stroke as indication for CEA were related to perioperative stroke. There was no link between perioperative stroke and patch type after correction for these factors. Patch type had no influence on operation time, clamp time, cranial nerve damage, hypertension, hematoma, infections, time to discharge, or early thromboembolic events. There were no significant differences between the Fluoropassiv and the venous group for cumulative mortality (respectively 4.4 vs 4.8%), patch occlusion (4.8 vs 2.2%), or stroke rate during 2 year follow-up (2.2 vs 2.4%). CONCLUSION This first clinical study with the Fluoropassiv thin wall carotid patch showed no enhanced thrombogenicity compared to a venous patch. The Fluoropassiv patch is not related to a higher rate of postoperative bleeding events either.

Relation between B-mode gray-scale median and clinical features of carotid stenosis vulnerability.

BACKGROUND Vulnerability of the carotid plaque might be useful as a predictor for ischemic stroke risk. The gray-scale median (GSM) of the carotid plaque at B-mode imaging has been described as an objective tool to quantify vulnerability. However, its use is disputed in the published literature. This study sought to validate the GSM as a predictor for carotid plaque vulnerability. METHODS We included 89 consecutive patients (64 men; mean ± SD age: 68 ± 1 years) who were evaluated for carotid endarterectomy. The GSM was derived from preoperative B-mode images and related to the presence of clinical symptoms, the presence of ipsilateral infarction on neuroimaging, and to the number of intraoperative ipsilateral microemboli (ME) detected by transcranial Doppler ultrasonography. In addition, we combined the GSM with its standard deviation (GSM-SD), which we hypothesized to be a measure for plaque heterogeneity and thereby vulnerability. RESULTS B-mode imaging revealed a wide variety in GSM among all plaques (median: 36; range: 6-89). The GSM could not be related to cardiovascular risk factors and was not different between symptomatic and asymptomatic patients (37.8 ± 8.9 vs 37.6 ± 17.1; P = 0.97). The GSM of plaques in patients with ipsilateral ischemic lesions on neuroimaging did also not differ from plaques in patients without (36.0 ± 14.6 vs 37.8 ± 16.9; P = 0.64). Finally, no relation between GSM and the presence of intraoperative ME (Spearman correlation; n = 73; ρ = 0.039; P = 0.75) was found. Combining GSM with its GSM-SD also could not identify more vulnerable plaques. CONCLUSIONS No relation was found between the GSM and any clinical, radiologic, or intra- and postoperative neurologic phenomena. These data showed no additional value of the use of GSM in evaluating plaque vulnerability.