Wojciech Poncyljusz

Molecular basis of human CD36 gene mutations.

CD36 is a transmembrane glycoprotein of the class B scavenger receptor family. The CD36 gene is located on chromosome 7 q11.2 and is encoded by 15 exons. Defective CD36 is a likely candidate gene for impaired fatty acid metabolism, glucose intolerance, atherosclerosis, arterial hypertension, diabetes, cardiomyopathy, Alzheimer disease, and modification of the clinical course of malaria. Contradictory data concerning the effects of antiatherosclerotic drugs on CD36 expression indicate that further investigation of the role of CD36 in the development of atherosclerosis may be important for the prevention and treatment of this disease. This review summarizes current knowledge of CD36 gene structure, splicing, and mutations and the molecular, metabolic, and clinical consequences of these phenomena.

The LVIS/LVIS Jr. stents in the treatment of wide-neck intracranial aneurysms: multicentre registry

Background Wide-necked intracranial aneurysms have been a challenge for endovascular techniques. With the advent of adjunctive devices such as balloons or stents, recanalisation rates have decreased secondary to better packing. Purpose The purpose of this registry was to evaluate the safety and effectiveness of the new Low-profiled Visualized Intraluminal Support LVIS and LVIS Jr. stents in the treatment of unruptured wide-neck intracranial aneurysms. Methods The LVIS or LVIS Jr. stent-assisted coil embolisation was performed in 78 patients harbouring 78 intracranial aneurysms. There were 59 aneurysms located in the anterior circulation and 19 in the posterior circulation. Clinical data and 6-month follow-up angiograms are presented. Results The LVIS and LVIS Jr. stents were successfully delivered to the target aneurysm; however, there were seven cases in which the LVIS/LVIS Jr. stents had suboptimal opening and apposition to the parent vessel wall. The overall technical success for all groups was 91% (71 of 78 stents). There was complete angiographic occlusion in 66 (85%) of 78 cases and residual neck remnants in 12 (15%) cases. All patients had 6-month angiographic follow-up, which demonstrated complete occlusion of the target aneurysm in 64 (82%) cases, residual neck remnants in 5 (6%) cases and there was aneurysm filling in 9 (12%) cases. Conclusions The LVIS/LVIS Jr. stent system is safe and effective for the treatment of wide-neck intracranial aneurysms, providing suitable support of the coil mass, which allows for a high level of occlusion with low rates of recanalisation and subsequent treatments.

Initial experience with implantation of novel dual layer flow-diverter device FRED

Flow-diverting stents can help treat complex and wide-necked cerebral aneurysms. The aim of the study was to evaluate initial experiences related to the safety and effectiveness of eight aneurysms treated with a new dual layer coverage designed flow-diverter device. In 2012 Fred flow-diverter devices were used to treat 8 unruptured wide neck (dome-neck ratio ≤ 1.5) and sidewall aneurysms in 6 patients. All aneurysms were located in the anterior circulation on the internal carotid artery (ICA). In 4 larger aneurysms (> 10 mm) one 3D coil in association with Fred was used to reduce potential incidence of postoperative subarachnoid haemorrhage (SAH). Dual antiplatelet therapy was administered before the procedure and continued for 3 months after it. Clinical parameters, aneurysm features and 3-month follow-up angiograms are presented. All 6 patients with 8 aneurysms were successfully stented with the Fred flow-diverter device and were discharged in generally good condition on dual-antiplatelet therapy. No complications were related to the procedure. In 5 cases digital subtraction angiography (DSA) control examination was performed after 3 months, showing complete occlusion of the aneurysms with patency of the parent artery. In 1 case thrombosis of the Fred occurred but without any clinical consequences because of cross-flow from the other side. Use of the Fred flow-diverter device was efficacious in all 8 treated cerebral aneurysms. The system seems to be promising as a flow diverter with certain characteristics, which allow for easy delivery and implantation. Further clinical evaluation with a larger group of patients is needed.

Bioactive versus bare platinum coils for the endovascular treatment of intracranial aneurysms: systematic review and meta-analysis of randomized clinical trials

Background Bioactive coils were introduced in 2002 in an attempt to improve aneurysm healing and durability of angiographic results. Evidence demonstrating superior efficacy to justify the routine use of bioactive coils over bare coils is limited. We compared the periprocedural and clinical outcome after bioactive and bare platinum coiling for intracranial aneurysms. Methods MEDLINE, EMBASE, Cochrane Library, and ISI Web of Knowledge Conference Proceedings Citation Index—Science were searched for randomized clinical trials (RCTs) comparing bioactive and bare coils. The methodological quality was evaluated to assess bias risk. Periprocedural outcomes and mid-term outcomes were compared. Results Five independent RCTs comparing bioactive (n=1084) and bare coils (n=1084) were identified. Periprocedural outcome was similar for both groups. Bioactive coiling increased the rate of complete aneurysm occlusion (47% vs 40%; RR 1.17 (95% CI 1.05 to 1.31); p=0.006) and reduced the rate of residual aneurysm neck at 10 months compared with bare coiling in the mid-term (26% vs 31%; RR 0.82 (95% CI 0.70 to 0.96); p=0.01). There were no differences in aneurysm recurrence, aneurysm rupture, stroke, neurological death, modified Rankin Scale score and reinterventions. Subgroup analysis for the three RCTs on hydrogel coils demonstrated reduction of residual aneurysms compared with bare coiling (25% vs 34%; RR 0.76 (95% CI 0.58 to 0.99); p=0.04). Conclusions Bioactive coils ensure a higher rate of medium-term complete aneurysm occlusion while reducing the rate of residual neck aneurysms compared with bare coiling in the mid-term. Hydrogel coils reduce residual aneurysms compared with bare coils. While there is level 1a evidence to show more complete aneurysm occlusion, longer term follow-up is needed to determine if this translates into clinical significance.

Is plasma soluble CD36 associated with cardiovascular risk factors in early onset coronary artery disease patients

Abstract Background and purpose. This is the first study to investigate the relationship between plasma concentration of soluble CD36 (sCD36) and CD36 gene polymorphisms as well as clinical and echocardiographic parameters in patients with early onset coronary artery disease (CAD). Methods. sCD36 concentrations were measured by the ELISA kits. CD36 sequence alterations detected by the DHPLC technique comprised single nucleotide substitutions: rs3173798, rs3211892, rs5956 and rs141680676. Results. There were significant negative correlations between sCD36 and red blood cell count, hemoglobin, hematocrit and glucose concentration, ApoB/ApoA1 ratio, patients’ weight and waist circumference, BMI, WHR, systolic blood pressure, MAP values, left ventricular end-diastolic diameter and volume, left atrium diameter, right ventricular end-diastolic diameter. There were significant positive correlations between sCD36 and patients’ age, mean corpuscular volume of erythrocytes, HDL-cholesterol, ApoA1 concentrations. Significantly higher CD36 plasma levels were found in female subgroup. There was no association between CD36 genotypes and sCD36 concentrations. Multiple linear regression analysis revealed that significant independent predictors of higher plasma sCD36 level were female gender, older age, lower serum glucose and lower RBC. Conclusion. The presented data suggest possible protective effects of higher sCD36 concentration in relation to metabolic syndrome components in CAD patients. Higher sCD36 concentration is also associated with lower risk of left ventricular hypertrophy, but on the other hand is a potential risk factor of impaired left ventricle diastolic function.

Analysis of human CD36 gene sequence alterations in the oxidized low-density lipoprotein-binding region using denaturing high-performance liquid chromatography.

Denaturing high-performance liquid chromatography (DHPLC) has been employed as a prescreening tool to reduce the amount of DNA sequencing. It could be a simple and cost-effective screening method for mutations and polymorphisms in exons 4, 5, and 6 of the CD36 gene, which encode the protein region responsible for the removal of oxidized low-density lipoprotein. Genomic DNA was isolated from 306 Caucasian infants of Polish origin. Six single-nucleotide substitutions were detected by DHPLC and confirmed by direct sequencing. The A591T, G550A, and C572T alterations have not been described so far. Each of two nonsynonymous substitutions (Asp184Asn, Pro191Leu) was found in one subject (0.2% minor allele frequency). The results suggest that nonsynonymous alterations in the analyzed CD36 region are rare in Caucasians. DHPLC is a specific and cost-effective technique that may prove to be particularly useful for the identification of polymorphisms and mutations in the CD36 gene.

Bare platinum coils vs. HydroCoil in the treatment of unruptured intracranial aneurysms-A single center randomized controlled study.

PURPOSE The HydroCoil Embolic System (HES) was developed to improve aneurysm filling to provide superior occlusion efficacy, reduce retreatment rates and enhance long-term durability. We performed a randomized clinical trial to compare the effectiveness of bare platinum coils (BPC) vs. HES for unruptured intracranial aneurysms. METHODS Ninety-six patients underwent endovascular coiling of unruptured intracranial aneurysms. The aneurysms were randomized equally to receive BPC or HES. Immediate angiographic results, number of coils used and complications were evaluated and all cases had 12-month follow-up angiography. RESULTS Immediate angiographic results demonstrated that 84.0% of aneurysms treated with HES were completely occluded compared to 76.1% of aneurysms treated with BPC (p=0.3310). The mean number of coils utilized to fill the aneurysm was significantly lower in the HES arm (5.04 vs. 6.93). Additional adjunctive techniques were performed in 51.1% of all cases. There were seven patients (7.3%) with postoperative complications during the study period. The coil type used during the treatment did not demonstrate any significant differences on the overall recurrence rate (HES - 18.0%, BPC - 17.4%, p=0.9712). There was a statistically significant difference in the aneurysm size and the neck width between completely occluded aneurysms and aneurysms with residual flow in both immediate angiographic and mid-term follow-up. CONCLUSIONS Overall, aneurysm size and neck width are the main risk factors associated with aneurysm recurrence. HES compared to BPC required less total number of coils to provide a denser aneurysm filling. However, there were equivocal results with both devices, at the mid-term angiographic follow-up.

Original Protocol Using Computed Tomographic Angiography for Diagnosis of Brain Death: A Better Alternative to Standard Two-Phase Technique?

BACKGROUND The application of computed tomographic angiography (CTA) for the diagnosis of brain death (BD) is limited because of the low sensitivity of the commonly used two-phase method consisting of assessing arterial and venous opacification at the 60th second after contrast injection. The hypothesis was that a reduction in the scanning delay might increase the sensitivity of the test. Therefore, an original technique using CTA was introduced and compared with catheter angiography as a reference. MATERIAL AND METHODS In a prospective multicenter trial, 84 clinically brain-dead patients were examined using CTA and catheter angiography. The sensitivities of original CTA technique, involving an arterial assessment at the 25th second and a venous assessment at the 40th second, and the standard CTA, involving an arterial and venous assessment at the 60th second, were compared to catheter angiography. RESULTS Catheter angiography results were consistent with the clinical diagnosis of BD in all cases. In comparison to catheter angiography, the sensitivity of original CTA technique was 0.93 (95%CI, 0.85-0.97; p<0.001) and 0.57 (95%CI, 0.46-0.68; p<0.001) for the standard protocol. The differences were statistically significant (p=0.03 for original CTA and p<0.001 for standard CTA). Decompressive craniectomy predisposes to a false-negative CTA result with a relative risk of 3.29 (95% CI, 1.76-5.81; p<0.001). CONCLUSIONS Our original technique using CTA for the assessment of the cerebral arteries during the arterial phase and the deep cerebral veins with a delay of 15 seconds is a highly sensitive test for the diagnosis of BD. This method may be a better alternative to the commonly used technique.

Association of CD36 gene polymorphisms with echo- and electrocardiographic parameters in patients with early onset coronary artery disease.

Introduction CD36 plays an important role in long-chain fatty acid homeostasis in skeletal muscle and the myocardium. CD36 deficiency may lead to reduced myocardial uptake of long-chain fatty acid. Therefore, different mutations of the CD36 gene may contribute to the clinical heterogeneity of cardiac hypertrophy. Material and methods The objective of the study was to investigate whether there is an association between the sequence changes in CD36 and echocardiographic and electrocardiographic parameters in Caucasian patients with early onset coronary artery disease. The study group comprised 100 patients. Electrocardiography and echocardiography were performed in all patients. Amplicons of exons 4 to 6 including fragments of introns were studied using the denaturing high-performance liquid chromatography technique. Results IVS3-6TC (rs3173798) heterozygotes had impaired left ventricle diastolic function. 573GA heterozygotes (rs5956) had higher frequency of pseudonormal left ventricular diastolic function and it was confirmed by the increase in wave A’ in the tissue Doppler. 591AT genotype was associated with borderline higher posterior wall end-diastolic thickness and lower E/A ratio. These results are consistent with electrocardiography parameters which could reflect left ventricular hypertrophy (higher RV5(6) and RV5(6) + SV1(2) parameters, depressed ST segments and tendency to longer Qtc II interval) in 591AT heterozygotes. Conclusions Detected variant alleles of CD36 may be associated with features of left ventricular hypertrophy and impaired diastolic function.

Visualization of novel microstents in patients with unruptured intracranial aneurysms with contrast-enhanced flat panel detector CT

OBJECTIVES The aim of our study was to evaluate the feasibility of contrast-enhanced flat panel detector CT (FPDCT) for visualizing the novel microstents implanted in patients with unruptured wide-necked intracranial aneurysms. METHODS Forty-four cases of patients who underwent stent assisted coiling at our department were retrospectively analyzed. In each case, FPDCT images were performed after stent and coils deployment and then assessed in the terms of stent struts and all radiopaque markers and tantalum strands visibility separately using a 3-grade scale (1 - inadequate, 2 - good, 3 - excellent). RESULTS Stent struts visibility was assessed to be inadequate for evaluation in all cases. All radiopaque markers and tantalum strands visibility was excellent in 61.4% and good in 38.6% of cases. We observed 4 (9.09%) cases of incomplete stent opening. Treated aneurysm size <10mm was an independent predictor of excellent stent all radiopaque markers and tantalum strands visibility (ρ=0.014). CONCLUSIONS Contrast-enhanced FPDCT is feasible for visualizing stents implanted in patients with intracranial aneurysms as it gives precise visualization of the relationships between the stent tantalum strands and the vessel wall. Stents used in the treatment of aneurysms ≥10 mm in size are worse visualized because of the coil streaking artifacts.