Contemporary Antithrombotic Treatment in Patients with Non-valvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: Rationale and Design of the Greek AntiPlatElet Atrial Fibrillation (GRAPE-AF) Registry

Background

Approximately 5 to 7% of patients undergoing percutaneous coronary intervention (PCI) for the treatment of coronary artery disease require chronic oral anticoagulation (OAC) on top of aspirin and a P2Y₁₂ receptor antagonist, mainly due to non-valvular atrial fibrillation (AF). The advent of non-vitamin K antagonist oral anticoagulants (NOACs) increased treatment options, while there is cumulative evidence that dual combination of a NOAC and a P2Y₁₂ receptor antagonist attenuates risk of bleeding, compared to traditional triple therapy, consisting of a vitamin K antagonist (VKA), aspirin, and a P2Y₁₂ receptor antagonist, without significantly compromising efficacy.

Study Design

Greek AntiPlatElet Atrial Fibrillation (GRAPE-AF, NCT 03362788) is an observational, nationwide study of non-valvular AF patients undergoing PCI, planning to enroll over 1-year period >?500 participants in 25 tertiary and non-tertiary PCI centers in Greece. Key data to be collected pre-discharge include demographics, detailed past medical history, and antithrombotic and concomitant treatment. Patients will be followed up at 1, 6, and 12 months post hospital discharge. Αt each follow-up visit, data on antithrombotic treatment, ischemic, bleeding, and adverse events will be collected. Study’s primary endpoint is clinically significant bleeding (Bleeding Academic Research Consortium, BARC ≥?2) at 12 months, between VKAs and NOACs-treated patients, analyzed using Cox proportional hazards models, by an intention-to-treat principle. An independent endpoint committee will adjudicate all clinical events.

Conclusions

This study aims at providing “real-world” information on current antithrombotic treatment patterns and clinical outcome of patients with non-valvular AF undergoing PCI.

     

Serum total adiponectin in nonalcoholic fatty liver disease: a systematic review and meta-analysis

Hypoadiponectinemia might represent a risk factor for nonalcoholic fatty liver disease (NAFLD). We performed a systematic review and meta-analysis to evaluate the serum total adiponectin levels in patients with simple nonalcoholic fatty liver (NAFL), those with nonalcoholic steatohepatitis (NASH), and controls. Data were extracted from PubMed, EMBASE, and Cochrane Central Register of Controlled Trials electronic databases (up to December 2009). The main outcome was the weighted mean differences (WMDs) in adiponectin between comparison groups. Twenty-eight studies were included in the systematic review. A meta-analysis of 27 studies that reported data on 2243 subjects (698 controls and 1545 patients with NAFLD) was performed. Controls had higher serum adiponectin compared with NAFL patients (12 studies, random-effects WMD [95% confidence interval {CI}] = 3.00 [1.57-4.43], I² = 80.4%) or NASH patients (19 studies, random-effects WMD [95% CI] = 4.75 [3.71-5.78], I² = 84.1%). The NASH patients demonstrated lower adiponectin compared with NAFL patients (19 studies, random-effects WMD [95% CI] = 1.81 [1.09-2.53], I² = 71.7%). By performing a meta-regression analysis, body mass index, age, sex, and type 2 diabetes mellitus failed to account for heterogeneity. However, the performance of liver biopsy on controls had significant effect on the outcome and accounted for 76.7%, 85.5%, and 22.8% of the between-study variance for comparisons between controls vs NAFLD, NAFL, and NASH patients, respectively. Based on liver histology, serum adiponectin levels are similar in NAFL patients and controls, but hypoadiponectinemia may play an important pathophysiological role in the progression from NAFL to NASH.     

Differential gene expression of bone marrow-derived CD34+ cells is associated with survival of patients suffering from myelodysplastic syndrome

One feature of the molecular pathology of myelodysplastic syndromes (MDS) is aberrant gene expression. Such aberrations may be related to patient survival, and may indicate to novel diagnostic and therapeutic targets. Therefore, we aimed at identifying aberrant gene expression that is associated with MDS and patient survival. Bone marrow-derived CD34+ hematopoietic progenitor cells from six healthy persons and 16 patients with MDS were analyzed on cDNA macroarrays comprising 1,185 genes. Thereafter, our patients were followed-up for 54 months. We found differential expression of genes that were hitherto unrecognized in the context of MDS. Differential expression of 10 genes was confirmed by quantitative real-time RT-PCR. Hierarchical cluster analysis facilitated the separation of CD34+ cells of normal donors from patients with MDS. More importantly, it also distinguished MDS-patients with short and long survival. Scrutinizing our cDNA macroarray data for genes that are associated with short survival, we found, among others, increased expression of six different genes that encode the proteasome subunits. On the other hand, the most differentially down-regulated gene was IEX-1, which encodes an anti-apoptotic protein. We confirmed its decreased expression on RNA and protein level in an independent validation set of patient samples. The presented data broadens our notion about the molecular pathology of MDS and may lend itself to better identify patients with short survival. Furthermore, our findings may help to define new molecular targets for drug development and therapeutic approaches for patients with poor prognosis.     

Lipidomics in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD), the most common chronic liver disorder in Western countries, comprises steatosis to nonalcoholic steatohepatitis (NASH), with the latter having the potential to progress to cirrhosis. The transition from isolated steatosis to NASH is still poorly understood, but lipidomics approach revealed that the hepatic lipidome is extensively altered in the setting of steatosis and steatohepatitis and these alterations correlate with disease progression. Recent data suggest that both quantity and quality of the accumulated lipids are involved in pathogenesis of NAFLD. Changes in glycerophospholipid, sphingolipid, and fatty acid composition have been described in both liver biopsies and plasma of patients with NAFLD, implicating that specific lipid species are involved in oxidative stress, inflammation, and cell death. In this article, we summarize the findings of main human lipidomics studies in NAFLD and delineate the currently available information on the pathogenetic role of each lipid class in lipotoxicity and disease progression.     

New insights into the effects of biomaterial chemistry and topography on the morphology of kidney epithelial cells

Increasing incidence of renal pathology in the western world calls for innovative research for the development of cell‐based therapies such as a bioartificial kidney (BAK) device. To fulfil the multitude of kidney functions, the core component of the BAK is a living membrane consisting of a tight kidney cell monolayer with preserved functional organic ion transporters cultured on a polymeric membrane surface. This membrane, on one side, is in contact with blood and therefore should have excellent blood compatibility, whereas the other side should facilitate functional monolayer formation. This work investigated the effect of membrane chemistry and surface topography on kidney epithelial cells to improve the formation of a functional monolayer. To achieve this, microtopographies were fabricated with high resolution and reproducibility on polystyrene films and on polyethersulfone‐polyvinyl pyrrolidone (PES‐PVP) porous membranes. A conditionally immortalized proximal tubule epithelial cell line (ciPTEC) was cultured on both, and subsequently, the cell morphology and monolayer formation were assessed. Our results showed that L‐dopamine coating of the PES‐PVP was sufficient to support ciPTEC monolayer formation. The polystyrene topographies with large features were able to align the cells in various patterns without significantly disruption of monolayer formation; however, the PES‐PVP topographies with large features disrupted the monolayer. In contrast, the PES‐PVP membranes with small features and with large spacing supported well the ciPTEC monolayer formation. In addition, the topographical PES‐PVP membranes were compatible as a substrate membrane to measure organic cation transporter activity in Transwell® systems. Copyright © 2016 John Wiley & Sons, Ltd.     

Electrophysiological markers predicting impeding AV‐block during ablation of atrioventricular nodal reentry tachycardia

1 Background

Radiofrequency (RF) ablation of the slow pathway (SP) in atrioventricular nodal reentry tachycardia (AVNRT) is occasionally complicated with atrioventricular block (AVB) often predicted by junctional beats (JB) with loss of ventriculo‐atrial (VA) conduction.

2 Methods

We analyzed retrospectively 153 patients undergoing ablation of SP for typical AVNRT. Patients were divided into two age groups: 127 ≤ 70 years and 26 > 70 years. We analyzed the interval between the atrial electrogram in the His‐bundle position and the distal ablation catheter [A(H)‐A(RFd)] and between the distal ablation catheter and the proximal coronary sinus catheter [A(RFd)‐A(CS)] before RF applications with and without JB. We evaluated if these intervals can be used as predictors of JB incidence and also of JB with loss of VA conduction. We also assessed if age influences the risk of loss of VA conduction.

3 Results

The A(H)‐A(RFd) and A(RFd)‐A(CS) intervals were significantly shorter in RF applications causing JB than those without JB (33 ± 11 ms vs 39 ± 9 ms, P < 0.001, 14 ± 9 ms vs 20 ± 7 ms, P < 0.001, respectively). The A(H)‐A(RFd) and A(RFd)‐A(CS) intervals were also significantly shorter in RFs causing JB with VA block than those with VA conduction (29 ± 11 ms vs 35 ± 11 ms, P < 0.001, 8 ± 8 ms vs 17 ± 8 ms, P < 0.001, respectively). Patients > 70 years had shorter intervals (36 ± 11 ms vs 29 ± 8 ms, P  =  0.012, 17 ± 8 ms vs 13 ± 7 ms, P  =  0.027, respectively), while VA block was more common in this age group.

4 Conclusions

The A(H)‐A(RFd) and A(RFd)‐A(CS) intervals can be used as markers for predicting JB occurrence as well as impending AVB. JB with loss of VA conduction occur more often in older patients possibly due to a higher position of SP.     

Endoglin (CD105) as a prognostic factor in head and neck squamous cell carcinoma

Endoglin (CD105) is a proliferation-associated protein abundantly expressed in angiogenic endothelial cells. Recent studies revealed that CD105 is intensively expressed in tumor vasculature, whereas intratumoral microvessel density (MVD) determined with the use of antibodies to CD105 has been found to be an important prognostic indicator for the outcome in a number of malignancies. In the current study, we investigated endoglin expression and evaluated MVD in 108 patients with head and neck squamous cell carcinoma. Endoglin was intensively expressed in intratumoral blood vessels, whilst lymphatics were rarely positive for CD105. High microvessel density was associated with a more aggressive tumor phenotype, including advanced clinical stage (p=0.008) and the presence of lymph node metastasis at the time of diagnosis (p=0.02). When microvessel counts were assessed for their prognostic values (high vs low MVD), there was a statistically significant difference in the overall survival among patients with tumors of the oral cavity and larynx (p<0.001) and in the disease-free survival among patients with tumors of the lower lip (p=0.01). The prognostic impact of microvessel density was not dependent on clinical stage or lymph node status. The results of the current study suggest that CD105 is a promising target for tumor imaging and prognosis.     

Effect of air-abrasion pre-treatment with bioactive glass 45S5 on enamel surface loss after erosion/abrasion challenge

ObjectivesThe aim of this in vitro study was to evaluate the effect of air-abrasion surface pre-treatment with bioactive glass (BAG) 45S5 on enamel surface loss after erosion/abrasion challenge.MethodsTwenty-four sound bovine incisors were used for this study. Four experimental groups (n = 12) were assigned as follows: Group 1 was the negative control group, Group 2 specimens were treated with a SnF₂ gel (positive control group), Group 3 specimens were air-abraded with BAG 45S5 (ProSylc) and Group 4 received both treatments. The specimens were submitted to erosion/abrasion challenge using a common soft drink. Enamel surface loss was evaluated using an optical profilometer. Additionally, surface roughness (VSI method) and surface microhardness (Vickers method) changes were evaluated, as well as SEM and EDS analyses were performed on enamel surface. The data were statistically analyzed using one-way ANOVA and Tukey’s post-hoc test at a level of significance a = 0.05.ResultsSurface pre-treatment with BAG 45S5 reduced surface loss in comparison with negative control group (p < 0.001), which exhibited the highest surface loss of the experimental groups (p < 0.05). The positive control group (SnF₂ treatment) and Group 4 specimens, which received both air-abrasion pre-treatment and SnF₂ treatment, presented the lowest surface loss (p < 0.05), but did not show significant differences to each other (p = 0.65).SignificanceAir-abrasion pre-treatment with BAG 45S5 may be beneficial as an in-office preventive method for the limitation of enamel erosive wear induced by excessive consumption of soft drinks. The clinical significance of the results regarding this preventive method should be confirmed by clinical studies.