Endovascular aortic repair versus open surgical repair for descending thoracic aortic disease a systematic review and meta-analysis of comparative studies.

OBJECTIVES: The purpose of this study was to determine whether thoracic endovascular aortic repair (TEVAR) reduces death and morbidity compared with open surgical repair for descending thoracic aortic disease. BACKGROUND: The role of TEVAR versus open surgery remains unclear. Metaregression can be used to maximally inform adoption of new technologies by utilizing evidence from existing trials. METHODS: Data from comparative studies of TEVAR versus open repair of the descending aorta were combined through meta-analysis. Metaregression was performed to account for baseline risk factor imbalances, study design, and thoracic pathology. Due to significant heterogeneity, registry data were analyzed separately from comparative studies. RESULTS: Forty-two nonrandomized studies involving 5,888 patients were included (38 comparative studies, 4 registries). Patient characteristics were balanced except for age, as TEVAR patients were usually older than open surgery patients (p = 0.001). Registry data suggested overall perioperative complications were reduced. In comparative studies, all-cause mortality at 30 days (odds ratio [OR]: 0.44, 95% confidence interval [CI]: 0.33 to 0.59) and paraplegia (OR: 0.42, 95% CI: 0.28 to 0.63) were reduced for TEVAR versus open surgery. In addition, cardiac complications, transfusions, reoperation for bleeding, renal dysfunction, pneumonia, and length of stay were reduced. There was no significant difference in stroke, myocardial infarction, aortic reintervention, and mortality beyond 1 year. Metaregression to adjust for age imbalance, study design, and pathology did not materially change the results. CONCLUSIONS: Current data from nonrandomized studies suggest that TEVAR may reduce early death, paraplegia, renal insufficiency, transfusions, reoperation for bleeding, cardiac complications, pneumonia, and length of stay compared with open surgery. Sustained benefits on survival have not been proven.

MR-IMPACT II: Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary artery disease Trial: perfusion-cardiac magnetic resonance vs. single-photon emission computed tomography for the detection of coronary artery disease: a comparative multicentre, multivendor trial.

Aims Perfusion-cardiac magnetic resonance (CMR) has emerged as a potential alternative to single-photon emission computed tomography (SPECT) to assess myocardial ischaemia non-invasively. The goal was to compare the diagnostic performance of perfusion-CMR and SPECT for the detection of coronary artery disease (CAD) using conventional X-ray coronary angiography (CXA) as the reference standard. Methods and results In this multivendor trial, 533 patients, eligible for CXA or SPECT, were enrolled in 33 centres (USA and Europe) with 515 patients receiving MR contrast medium. Single-photon emission computed tomography and CXA were performed within 4 weeks before or after CMR in all patients. The prevalence of CAD in the sample was 49%. Drop-out rates for CMR and SPECT were 5.6 and 3.7%, respectively (P = 0.21). The primary endpoint was non-inferiority of CMR vs. SPECT for both sensitivity and specificity for the detection of CAD. Readers were blinded vs. clinical data, CXA, and imaging results. As a secondary endpoint, the safety profile of the CMR examination was evaluated. For CMR and SPECT, the sensitivity scores were 0.67 and 0.59, respectively, with the lower confidence level for the difference of +0.02, indicating superiority of CMR over SPECT. The specificity scores for CMR and SPECT were 0.61 and 0.72, respectively (lower confidence level for the difference: -0.17), indicating inferiority of CMR vs. SPECT. No severe adverse events occurred in the 515 patients. Conclusion In this large multicentre, multivendor study, the sensitivity of perfusion-CMR to detect CAD was superior to SPECT, while its specificity was inferior to SPECT. Cardiac magnetic resonance is a safe alternative to SPECT to detect perfusion deficits in CAD.

Adeno-associated virus (AAV) vectors achieve prolonged transgene expression in mouse myocardium and arteries in vivo: a comparative study with adenovirus vectors.

Plasmid DNA and adenovirus vectors currently used in cardiovascular gene therapy trials are limited by low efficiency and short-lived transgene expression, respectively. Recombinant adeno-associated virus (AAV) has recently emerged as an attractive vector for cardiovascular gene therapy. In the present study, we have compared AAV and adenovirus vectors with respect to gene transfer efficiency and the duration of transgene expression in mouse hearts and arteries in vivo. AAV vectors (titer: 5 x 10(8) transducing units (TU)/ml) and adenovirus vectors (1.2 x 10(10) TU/ml) expressing a green fluorescent protein (EGFP) gene were injected either intramyocardially (n=32) or intrapericardially (n=3) in CD-1 mice. Hearts were harvested at varying time intervals (3 days to 1 year) after gene delivery. After intramyocardial injection of 5 microl virus stock solution, cardiomyocyte transduction rates with AAV vectors were 4-fold lower than with adenovirus vectors (1.5% (range: 0.5-2.6%) vs. 6.2% (range: 2.7-13.7%); P<0.05), but similar to titer-matched adenovirus vectors (0.7%; range: 0.2-1.2%). AAV-mediated EGFP expression lasted for at least 1 year. AAV vectors instilled into the pericardial space transduced epicardial myocytes. Arterial gene transfer was studied in mouse carotids (n=26). Both vectors selectively transduced endothelial cells after luminal instillation. Transduction rates with AAV vectors were 8-fold lower than with adenovirus vectors (2.0% (range: 0-3.2%) vs. 16.2% (range: 8.5-20.2%); P<0.05). Prolonged EGFP expression was observed after AAV but not adenovirus-mediated gene transfer. In conclusion, AAV vectors deliver and express genes for extended periods of time in the myocardium and arterial endothelium in vivo. AAV vectors may be useful for gene therapy approaches to chronic cardiovascular diseases.

Comparative vascular and renal tabular effects of angiotensin II receptor blockers combined with a thiazide diurectic in humans

Rapport de synthese :Comparaison des effets vasculaires et tubulaires rénaux de plusieurs antagonistes des récepteurs de |'angiotensine II en combinaison avec un diurétique thiazidique chez l'humainObjectif : Le but de ce travail était d'investiguer si les antagonistes des récepteurs AT1 de l'angiotensine II (ARA2) entraînent un blocage équivalent des récepteurs au niveau vasculaire et au niveau rénal, en particulier lorsque le système rénine- angiotensine est stimulé par l'administration d'un diurétique thiazidique. Méthode : trente volontaires masculins en bonne santé ont participé à cette étude randomisée, contrôlée, en simple insu. Nous avons mesuré les variations de pression artérielle, d'hémodynamique rénale ainsi que la réponse tubulaire rénale à une perfusion d'angiotensine II 3ng/kg/min administrée sur 1 heure. Ceci avant traitement puis après sept jours d'administration, 24 heures après la dernière dose de médicament. Nous avons comparé l'irbésartan 300 mg seul ou en association avec 12.5 ou 25 mg d'hydrochlorothiazide. (irbésartan 300/12.5 ; irbésartan 300/25). Nous avons également comparé les effets de l'irbésartan 300/25 au losartan 100 mg, au valsartan 160 mg ainsi qu'à l'olmésartan 20 mg, tous administrés avec 25 mg d'hydrochlorothiazide. Chaque participant a été randomisé pour recevoir 2 traitements de 7 jours espacés d'une période d'une semaine sans traitement. Résultats: La réponse de la pression artérielle à |'angiotensine II exogène était bloquée >90% avec l'irbésartan 300 mg seul ou en association avec le diurétique. Il en était de même avec l'olmésartan 20/25. Par contre le blocage n'était que de 60% environ dans les groupes valsartan 160/25 et losartan 100/25. Au niveau rénal, |'angiotensine II exogène réduisait le flux plasmatique rénal de 36% en pré- traitement. Dans les groupes recevant l'irbésartan 300 mg et l'olmésartan 20 mg associés à l'hydrochlorothiazide 25 mg, la vasoconstriction rénale était bloquée presque entièrement alors qu'el|e ne |'était que partiellement avec le valsartan 160/25 et le losartan 100/25 (34 et 45%, respectivement). En pré-traitement, au niveau tubulaire, l'angiotensine II exogène réduisait le volume urinaire de 84% et l'excrétion urinaire de sodium de 65 %. Les effets tubulaires n'étaient que partiellement bloqués par l'administration d'ARA2. Conclusion: Ces résultats démontrent que les ARA; aux doses maximales recommandées ne bloquent pas aussi efficacement les récepteurs ATI au niveau tubulaire qu'au niveau vasculaire. Cette observation pourrait constituer une justification à l'hypothèse selon laquelle des doses plus importantes d'ARA2 seraient nécessaires afin d'obtenir une meilleure protection d'organe. De plus, nos résultats confirment qu'i| y a d'importantes différences entre les ARA2, relatives à leur capacité d'induire un blocage prolongé sur 24 heures des récepteurs AT1 au niveau vasculaire et tubulaire.

Viral inhibitor of apoptosis vFLIP/K13 protects endothelial cells against superoxide-induced cell death.

Human herpesvirus 8 (HHV-8) is the etiological agent of Kaposi's sarcoma (KS). HHV-8 encodes an antiapoptotic viral Fas-associated death domain-like interleukin-1beta-converting enzyme-inhibitory protein (vFLIP/K13). The antiapoptotic activity of vFLIP/K13 has been attributed to an inhibition of caspase 8 activation and more recently to its capability to induce the expression of antiapoptotic proteins via activation of NF-kappaB. Our study provides the first proteome-wide analysis of the effect of vFLIP/K13 on cellular-protein expression. Using comparative proteome analysis, we identified manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant and an important antiapoptotic enzyme, as the protein most strongly upregulated by vFLIP/K13 in endothelial cells. MnSOD expression was also upregulated in endothelial cells upon infection with HHV-8. Microarray analysis confirmed that MnSOD is also upregulated at the RNA level, though the differential expression at the RNA level was much lower (5.6-fold) than at the protein level (25.1-fold). The induction of MnSOD expression was dependent on vFLIP/K13-mediated activation of NF-kappaB, occurred in a cell-intrinsic manner, and was correlated with decreased intracellular superoxide accumulation and increased resistance of endothelial cells to superoxide-induced death. The upregulation of MnSOD expression by vFLIP/K13 may support the survival of HHV-8-infected cells in the inflammatory microenvironment in KS.

Comparative assessment of intimal hyperplasia development after 14 days in two different experimental settings: tissue culture versus ex vivo continuous perfusion of human saphenous vein.

BACKGROUND: Intimal hyperplasia (IH) is a vascular remodeling process which often leads to failure of arterial bypass or hemodialysis access. Experimental and clinical work have provided insight in IH development; however, further studies under precise controlled conditions are required to improve therapeutic strategies to inhibit IH development. Ex vivo perfusion of human vessel segments under standardized hemodynamic conditions may provide an adequate experimental approach for this purpose. Therefore, chronically perfused venous segments were studied and compared to traditional static culture procedures with regard to functional and histomorphologic characteristics as well as gene expression. MATERIALS AND METHODS: Static vein culture allowing high tissue viability was performed as previously described. Ex vivo vein support system (EVVSS) was performed using a vein support system consisting of an incubator with a perfusion chamber and a pump. EVVSS allows vessel perfusion under continuous flow while maintaining controlled hemodynamic conditions. Each human saphenous vein was divided in two parts, one cultured in a Pyrex dish and the other part perfused in EVVSS for 14days. Testing of vasomotion, histomorphometry, expression of CD 31, Factor VIII, MIB 1, alpha-actin, and PAI-l were determined before and after 14days of either experimental conditions. RESULTS: Human venous segments cultured under traditional or perfused conditions exhibited similar IH after 14 days as shown by histomorphometry. Smooth-muscle cell (SMC) was preserved after chronic perfusion. Although integrity of both endothelial and smooth-muscle cells appears to be maintained in both culture conditions as confirmed by CD31, factor VIII, and alpha-actin expression, a few smooth-muscle cells in the media stained positive for factor VIII. Cell-proliferation marker MIB-1 was also detected in the two settings and PAI-1 mRNA expression and activity increased significantly after 14 days of culture and perfusion. CONCLUSION: This study demonstrates the feasibility to chronically perfuse human vessels under sterile conditions with preservation of cellular integrity and vascular contractility. To gain insights into the mechanisms leading to IH, it will now be possible to study vascular remodeling not only under static conditions but also in hemodynamic environment mimicking as closely as possible the flow conditions encountered in reconstructive vascular surgery.

Measurement Errors Should Always Be Incorporated in Phylogenetic Comparative Analysis

The evolution of continuous traits is the central component of comparative analyses in phylogenetics, and the comparison of alternative models of trait evolution has greatly improved our understanding of the mechanisms driving phenotypic differentiation. Several factors influence the comparison of models, and we explore the effects of random errors in trait measurement on the accuracy of model selection. We simulate trait data under a Brownian motion model (BM) and introduce different magnitudes of random measurement error. We then evaluate the resulting statistical support for this model against two alternative models: Ornstein-Uhlenbeck (OU) and accelerating/decelerating rates (ACDC). Our analyses show that even small measurement errors (10%) consistently bias model selection towards erroneous rejection of BM in favour of more parameter-rich models (most frequently the OU model). Fortunately, methods that explicitly incorporate measurement errors in phylogenetic analyses considerably improve the accuracy of model selection. Our results call for caution in interpreting the results of model selection in comparative analyses, especially when complex models garner only modest additional support. Importantly, as measurement errors occur in most trait data sets, we suggest that estimation of measurement errors should always be performed during comparative analysis to reduce chances of misidentification of evolutionary processes.

Analyse comparative des ressources financières des partis politiques suisses

Les partis politiques ont comme vocation de structurer le débat démocratique et de constituer un trait d'union entre le citoyen et l'Etat. En Suisse, ils sont fortement sollicités en raison de l'importante quantité de scrutins organisés chaque année aux échelons communal, cantonal et national, mais leur organisation reste très peu professionnalisée. Comme ils doivent par ailleurs faire face à l'effritement de leur base partisane et à l'inflation des coûts de la politique, le risque est grand qu'ils soient mis en difficulté dans l'accomplissement de leur tâche d'intégration et de formation de l'opinion. Cette étude se concentre sur les pratiques de financement des partis cantonaux et nationaux du PDC, du PRD, du PS, de l'UDC et des Verts. S'appuyant sur les données empriques récoltées en 1997 et en 2007, elle décrit dans quelle mesure les moyens financiers des partis ont évolué au cours des dix dernières années. Les analyses portent sur le volume et l'origine des fonds et elles permettent notamment de saisir comment s'articulent les clivages en matière de financement. Die politischen Parteien haben die Aufgabe, die demokratische Debatte zu strukturieren und ein verbindendes Element zwischen dem Bürger und dem Staat zu bilden. In der Schweiz werden sie angesichts der grossen Anzahl jährlich auf kommunaler, kantonaler und nationaler Ebene durchgeführten Wahlgänge besonders stark beansprucht, ihre Organisationen sind aber wenig professionalisiert. Da sich die Parteien heute mit abnehmenden Parteienbindungen und steigenden Kosten der Politik konfrontiert sehen, steigt das Risiko, dass sie ihre Aufgaben der Integration und der politischen Meinungsbildung kaum mehr wahrnehmen können. Diese Arbeit konzentriert sich auf die Finanzierungspraktiken der kantonalen und nationalen Parteien CVP, FDP, SP, SVP und Grüne. Die Analysen stützen sich ab auf empirische Angaben zu Herkunft und Umfang der Parteifinanzen, die in den Jahren 1997 und 2007 erhoben wurden und erlauben es, die Unterschiede hinsichtlich der Finanzierung zu erläutern.