Panagiotis Kougias

Long-Term Comparison of Endovascular and Open Repair of Abdominal Aortic Aneurysm

BACKGROUND Whether elective endovascular repair of abdominal aortic aneurysm reduces long-term morbidity and mortality, as compared with traditional open repair, remains uncertain. METHODS We randomly assigned 881 patients with asymptomatic abdominal aortic aneurysms who were candidates for both procedures to either endovascular repair (444) or open repair (437) and followed them for up to 9 years (mean, 5.2). Patients were selected from 42 Veterans Affairs medical centers and were 49 years of age or older at the time of registration. RESULTS More than 95% of the patients underwent the assigned repair. For the primary outcome of all-cause mortality, 146 deaths occurred in each group (hazard ratio with endovascular repair versus open repair, 0.97; 95% confidence interval [CI], 0.77 to 1.22; P=0.81). The previously reported reduction in perioperative mortality with endovascular repair was sustained at 2 years (hazard ratio, 0.63; 95% CI, 0.40 to 0.98; P=0.04) and at 3 years (hazard ratio, 0.72; 95% CI, 0.51 to 1.00; P=0.05) but not thereafter. There were 10 aneurysm-related deaths in the endovascular-repair group (2.3%) versus 16 in the open-repair group (3.7%) (P=0.22). Six aneurysm ruptures were confirmed in the endovascular-repair group versus none in the open-repair group (P=0.03). A significant interaction was observed between age and type of treatment (P=0.006); survival was increased among patients under 70 years of age in the endovascular-repair group but tended to be better among those 70 years of age or older in the open-repair group. CONCLUSIONS Endovascular repair and open repair resulted in similar long-term survival. The perioperative survival advantage with endovascular repair was sustained for several years, but rupture after repair remained a concern. Endovascular repair led to increased long-term survival among younger patients but not among older patients, for whom a greater benefit from the endovascular approach had been expected. (Funded by the Department of Veterans Affairs Office of Research and Development; OVER ClinicalTrials.gov number, NCT00094575.).

Comparison of percutaneous ultrasound-accelerated thrombolysis versus catheter-directed thrombolysis in patients with acute massive pulmonary embolism.

Acute massive pulmonary embolism (PE) is a life-threatening condition that requires prompt and aggressive interventions, including anticoagulation, catheter-directed thrombolysis (CDT), mechanical thrombectomy, or surgical thromboembolectomy. The aim of this study was to evaluate the treatment outcome in patients with massive PE who were treated with either ultrasound-accelerated thrombolysis using the EkoSonic Endovascular System (EKOS) or CDT intervention. During a recent 10-year period, the clinical records of all patients with massive PE undergoing catheter-directed interventions were evaluated. Patients were divided into two treatment groups: EKOS versus CDT interventions. Comparisons were made with regard to the treatment outcome between the two groups. Twenty-five patients underwent 33 catheter-directed interventions for massive PE during the study period. Among them, EKOS or CDT was performed in 15 (45%) and 18 (55%) procedures, respectively. In the EKOS group, complete thrombus removal was achieved in 100% cases. In the CDT cohort, complete or partial thrombus removal was accomplished in 7 (50%) and 2 (14%) cases, respectively. Comparing treatment success based on thrombus removal, EKOS treatment resulted in an improved treatment outcome compared with the CDT group (p ≤ .02). The mean time of thrombolysis in EKOS and CDT group was 17.4 ± 5.23 and 25.3 ± 7.35 hours, respectively (p = .03). The mortality rate in the EKOS and CDT group was 9.1% and 14.2%, respectively (not significant). Treatment-related hemorrhagic complication rates in the EKOS and CDT group were 0% and 21.4%, respectively (p = .02). A significant reduction in Miller scores was noted in both groups following catheter-based interventions. No significant difference in relative Miller score improvement was observed between groups. Ultrasound-accelerated thrombolysis using the EkoSonic system is an effective treatment modality in patients with acute massive PE. When compared with CDT, this treatment modality provides similar treatment efficacy with reduced thrombolytic infusion time and treatment-related complications.

Normal Human Fibroblasts Express Pattern Recognition Receptors for Fungal (1→3)-β-d-Glucans

ABSTRACT Fungal cell wall glucans nonspecifically stimulate various aspects of innate immunity. Glucans are thought to mediate their effects via interaction with membrane receptors on macrophages, neutrophils, and NK cells. There have been no reports of glucan receptors on nonimmune cells. We investigated the binding of a water-soluble glucan in primary cultures of normal human dermal fibroblasts (NHDF). Membranes from NHDF exhibited saturable binding with an apparent dissociation constant (KD) of 8.9 ± 1.9 μg of protein per ml and a maximum binding of 100 ± 8 resonance units. Competition studies demonstrated the presence of at least two glucan binding sites on NHDF. Glucan phosphate competed for all binding sites, with a KD of 5.6 μM (95% confidence interval [CI], 3.0 to 11 μM), while laminarin competed for 69% ± 6% of binding sites, with a KD of 3.7 μM (95% CI, 1.9 to 7.3 μM). Glucan (1 μg/ml) stimulated fibroblast NF-κB nuclear binding activity and interleukin 6 (IL-6) gene expression in a time-dependent manner. NF-κB was activated at 4, 8, and 12 h, while IL-6 mRNA levels were increased by 48% at 8 h. This is the first report of pattern recognition receptors for glucan on human fibroblasts and the first demonstration of glucan binding sites on cells other than leukocytes. It also provides the first evidence that glucans can directly modulate the functional activity of NHDF. These results provide new insights into the mechanisms by which the host recognizes and responds to fungal (1→3)-β-d-glucans and suggests that the response to glucans may not be confined to cells of the immune system.

Biogas Upgrading via Hydrogenotrophic Methanogenesis in Two-Stage Continuous Stirred Tank Reactors at Mesophilic and Thermophilic Conditions

This study proposes an innovative setup composed by two stage reactors to achieve biogas upgrading coupling the CO2 in the biogas with external H2 and subsequent conversion into CH4 by hydrogenotrophic methanogenesis. In this configuration, the biogas produced in the first reactor was transferred to the second one, where H2 was injected. This configuration was tested at both mesophilic and thermophilic conditions. After H2 addition, the produced biogas was upgraded to average CH4 content of 89% in the mesophilic reactor and 85% in the thermophilic. At thermophilic conditions, a higher efficiency of CH4 production and CO2 conversion was recorded. The consequent increase of pH did not inhibit the process indicating adaptation of microorganisms to higher pH levels. The effects of H2 on the microbial community were studied using high-throughput Illumina random sequences and full-length 16S rRNA genes extracted from the total sequences. The relative abundance of archaeal community markedly increased upon H2 addition with Methanoculleus as dominant genus. The increase of hydrogenotrophic methanogens and syntrophic Desulfovibrio and the decrease of aceticlastic methanogens indicate a H2-mediated shift toward the hydrogenotrophic pathway enhancing biogas upgrading. Moreover, Thermoanaerobacteraceae were likely involved in syntrophic acetate oxidation with hydrogenotrophic methanogens in absence of aceticlastic methanogenesis.

miRNAs: roles and clinical applications in vascular disease.

miRNAs are small, endogenously expressed noncoding RNAs that regulate gene expression, mainly at the post-transcriptional level, via degradation or translational inhibition of their target mRNAs. Functionally, an individual miRNA can regulate the expression of multiple target genes. The study of miRNAs is rapidly growing and recent studies have revealed a significant role of miRNAs in vascular biology and disease. Many miRNAs are highly expressed in the vasculature, and their expression is dysregulated in diseased vessels. Several miRNAs have been found to be critical modulators of vascular pathologies, such as atherosclerosis, lipoprotein metabolism, inflammation, arterial remodeling, angiogenesis, smooth muscle cell regeneration, hypertension, apoptosis, neointimal hyperplasia and signal transduction pathways. Thus, miRNAs may serve as novel biomarkers and/or therapeutic targets for vascular disease. This article summarizes the current studies related to the disease correlations and functional roles of miRNAs in the vascular system and discusses the potential applications of miRNAs in vascular disease.

Management of chronic mesenteric ischemia. The role of endovascular therapy.

Chronic mesenteric ischemia is an uncommon disorder manifested most commonly as abdominal pain. Surgical revascularization has traditionally been the treatment of choice. Endovascular management of this entity was originally attempted as an alternative for high-risk patients. Improvements in stent technology, refinement in technique, and increased efficiency of antiplatelet regimens have, over time, increased the popularity of this minimally invasive approach. We present a review of the available series on endovascular treatment of chronic mesenteric ischemia, with emphasis on short- and longterm outcome and morbidity and mortality results. Principles of operative technique and controversial issues and topics of interest are also discussed.

Deeper insight into the structure of the anaerobic digestion microbial community; the biogas microbiome database is expanded with 157 new genomes

This research aimed to better characterize the biogas microbiome by means of high throughput metagenomic sequencing and to elucidate the core microbial consortium existing in biogas reactors independently from the operational conditions. Assembly of shotgun reads followed by an established binning strategy resulted in the highest, up to now, extraction of microbial genomes involved in biogas producing systems. From the 236 extracted genome bins, it was remarkably found that the vast majority of them could only be characterized at high taxonomic levels. This result confirms that the biogas microbiome is comprised by a consortium of unknown species. A comparative analysis between the genome bins of the current study and those extracted from a previous metagenomic assembly demonstrated a similar phylogenetic distribution of the main taxa. Finally, this analysis led to the identification of a subset of common microbes that could be considered as the core essential group in biogas production.

Effect of organic loading rate and feedstock composition on foaming in manure-based biogas reactors

Foaming is one of the major problems that occasionally occur in biogas plants, affecting negatively the overall digestion process. In the present study, the effect of organic loading rate (OLR) and feedstock composition on foaming was elucidated in continuous reactor experiments. By stepwise increasing the OLR and the concentration of proteins or lipids in the substrate, foaming in biogas reactors was investigated. No foam formation was observed at the OLR of 3.5 g volatile solids/(L-reactor·day). Organic loading was the main factor affecting foam formation in manure digester, while the organic composition, such as content of proteins or lipids were factors that in combination with the organic loading were triggering foaming. More specifically, gelatine could initiate foam formation at a lower OLR than sodium oleate. Moreover, the volume of foam produced by gelatine was relatively stable and was not increased when further increasing either OLR or gelatine concentration in the feed.

Defensins and cathelicidins: Neutrophil peptides with roles in inflammation, hyperlipidemia and atherosclerosis

Atherosclerosis is a disease that begins in fetal life and represents a leading cause of morbidity and mortality associated with significant socioeconomic consequences. A central concept with regard to its pathogenesis is that of endothelial cell dysfunction, which is associated with the release of a large number of mediators secreted by leukocytes that are present in large numbers at the sites of atheroma formation. Neutrophil peptides defensins and cathelicidins are essential elements of the innate immunity and have been present in high concentrations in atherosclerotic plaques in humans. Recently, their role as potential mediators of vascular disease was investigated. Defensins are involved in the lipoprotein metabolism in the vessel wall, favoring LDL and lipoprotein (a) accumulation and modification in the endothelium and the extracellular matrix. They also interfere with the vascular smooth muscle cell function, exhibit prothrombotic activity, and play an inhibitory role in various phases of angiogenesis. Cathelicidins were recently found to enhance endothelial proliferation in cultures, induce functionally significant angiogenesis in animal models, and regulate endothelial cell apoptosis. Further study of these peptides could provide useful insight in the relationship between inflammation and atherosclerosis and is anticipated to have therapeutic and prognostic ramifications.

Clinical Outcome of Staged Versus Combined Treatment Approach of Hybrid Repair of Thoracoabdominal Aortic Aneurysm With Visceral Vessel Debranching and Aortic Endograft Exclusion

Although visceral vessel debranching and endovascular aneurysm exclusion represents a hybrid treatment approach in patients with thoracoabdominal aortic aneurysm, the effect of timing with regard to the visceral debranching procedure and endovascular aneurysm exclusion in this treatment strategy remains unclear. In this study, the authors analyzed their recent institutional experience of visceral debranching and aneurysm stent-grafting procedures. Specifically, the authors compared the effect of staged (n = 27) versus combined (n = 31) hybrid treatment in patients with complex aortic aneurysms. This study showed a higher incidence of renal insufficiency in patients undergoing a combined hybrid repair than the staged hybrid approach. The possibility of aneurysm rupture may exist in the staged treatment approach if the duration of staged repair is prolonged. The combined hybrid treatment strategy should be performed with caution as it is associated with significantly higher complication rates than the staged hybrid treatment modality.