Parkinson’s disease is an incurable neurodegenerative disorder caused by the aggregation of α-synuclein (AS). This amyloid protein contains a 12-residue-long segment, AS71–82, that triggers AS ...pathological aggregation. This peptide is then essential to better understand the polymorphism and the dynamics of formation of AS fibrillar structures. In this work, vibrational circular dichroism showed that AS71–82 is random coil in solution and forms parallel β-sheet fibrillar aggregates in the presence of anionic vesicles. Vibrational circular dichroism, with transmission electronic microscopy, revealed that the fibrillar structures exhibit a nanoscale tape-like morphology with a preferential supramolecular helicity. Whereas the structure handedness of some other amyloid peptides has been shown to be driven by pH, that of AS71–82 is controlled by peptide concentration and peptide-to-lipid (P:L) molar ratio. At low concentrations and low P:L molar ratios, AS71–82 assemblies have a left-twisted handedness, whereas at high concentrations and high P:L ratios, a right-twisted handedness is adopted. Left-twisted assemblies interconvert into right-twisted ones with time, suggesting a maturation of the amyloid structures. As fibril species with two chiralities have also been reported previously in Parkinson’s disease Lewy bodies and fibrils, the present results seem relevant to better understand AS amyloid assembly and fibrillization in vivo. From a diagnosis or therapeutic point of view, it becomes essential that future fibril probes, inhibitors, or breakers target pathological assemblies with specific chirality and morphology, in particular, because they may change with the stage of the disease.
Self-Medication in Animals de Roode, Jacobus C.; Lefèvre, Thierry; Hunter, Mark D.
Science (American Association for the Advancement of Science),
04/2013, Volume:
340, Issue:
6129
Journal Article
Peer reviewed
The concept of antiparasite self-medication in animals typically evokes images of chimpanzees seeking out medicinal herbs to treat their diseases (1, 2). These images stem partly from the belief that ...animals can medicate themselves only when they have high cognitive abilities that allow them to observe, learn, and make conscious decisions (3). However, any concept of self-medication based solely on learning is inadequate. Many animals can use medication through innate rather than learned responses. The growing list of animal pharmacists includes moths (4), ants (5), and fruit flies (6). The fact that these animals self-medicate has profound implications for the ecology and evolution of animal hosts and their parasites.
Abstract Background The SAPIEN 3 (Edwards Lifesciences Inc., Irvine, California) transcatheter valve incorporates features designed to address the well-known deficiencies of transcatheter aortic ...valve replacement (TAVR). An ultra–low-profile delivery system facilitates safe, controlled, and accurate implantation and an external seal minimizes paravalvular regurgitation. Objectives The study evaluated whether TAVR with this third-generation valve would be a viable alternative to high- or intermediate-risk surgery for severe aortic stenosis. Methods The prospective study enrolled 150 patients at 16 sites in Europe and Canada. Clinical and echocardiographic outcomes were assessed at baseline, post-procedure, and 30 days. New sizing recommendations were developed during the course of the study. Results Patients were 83.6 ± 5.0 years of age, with multiple comorbidities reflected by a Society of Thoracic Surgeons score of 7.4 ± 4.5% and logistic EuroSCORE of 21.6 ± 12.3%. A transfemoral approach was chosen in 64.0% and alternative access (transapical/direct aortic) in the remainder. At 30 days, paravalvular regurgitation was none to mild in 96.4% and moderate in 3.5%. No patient had severe regurgitation. Transfemoral implantation was associated with low mortality (2.1%), no disabling stroke (0.0%), and fully percutaneous access and closure in 95.8%. Nontransfemoral alternative access was associated with higher rates of mortality (11.6%) and stroke (5.6%). Conclusions This third-generation device addresses major deficiencies of earlier valves in terms of ease of use, accuracy of positioning, and paravalvular sealing. The rates of mortality and stroke with transfemoral access are among the lowest reported and support further evaluation as an alternative to open surgery in intermediate-risk patients. (Safety and Performance Study of the Edwards SAPIEN 3 Transcatheter Heart Valve SAPIEN3; NCT01808287 )
Transcatheter aortic valve implantation was developed to mitigate the mortality and morbidity associated with high-risk traditional aortic valve replacement. The Edwards SAPIEN valve was approved for ...transcatheter aortic valve implantation transfemoral delivery in the European Union in November 2007 and for transapical delivery in January 2008.
The SAPIEN Aortic Bioprosthesis European Outcome (SOURCE) Registry was designed to assess the initial clinical results of the Edwards SAPIEN valve in consecutive patients in Europe after commercialization. Cohort 1 consists of 1038 patients enrolled at 32 centers. Patients who were treated with the transapical approach (n=575) suffered more comorbidities than the transfemoral patients (n=463), resulting in a significantly higher logistic EuroSCORE (29.1% versus 25.7%; P<0.001). Therefore, these groups are considered different, and outcomes cannot be compared. Overall short-term procedural success was observed in 93.8%. The incidence of valve embolization was 0.3% (n=3), and coronary obstruction was reported for 0.6% (n=6 cases). Incidence of stroke was 2.5% and similar for both procedural approaches. Thirty-day mortality was 6.3% in transfemoral patients and 10.3% in transapical patients. The occurrence of vascular complications was not a predictor of <30-day mortality in the transfemoral population.
Technical proficiency can be learned and adapted readily as demonstrated by the short-term procedural success rate and low 30-day mortality rates reported in the SOURCE Registry. Specific complication management and refinement of patient selection are needed to further improve outcomes.
Transcatheter aortic-valve implantation (TAVI) is an emerging intervention for the treatment of high-risk patients with severe aortic stenosis and coexisting illnesses. We report the results of a ...prospective multicenter study of the French national transcatheter aortic-valve implantation registry, FRANCE 2.
All TAVIs performed in France, as listed in the FRANCE 2 registry, were prospectively included in the study. The primary end point was death from any cause.
A total of 3195 patients were enrolled between January 2010 and October 2011 at 34 centers. The mean (±SD) age was 82.7±7.2 years; 49% of the patients were women. All patients were highly symptomatic and were at high surgical risk for aortic-valve replacement. Edwards SAPIEN and Medtronic CoreValve devices were implanted in 66.9% and 33.1% of patients, respectively. Approaches were either transarterial (transfemoral, 74.6%; subclavian, 5.8%; and other, 1.8%) or transapical (17.8%). The procedural success rate was 96.9%. Rates of death at 30 days and 1 year were 9.7% and 24.0%, respectively. At 1 year, the incidence of stroke was 4.1%, and the incidence of periprosthetic aortic regurgitation was 64.5%. In a multivariate model, a higher logistic risk score on the European System for Cardiac Operative Risk Evaluation (EuroSCORE), New York Heart Association functional class III or IV symptoms, the use of a transapical TAVI approach, and a higher amount of periprosthetic regurgitation were significantly associated with reduced survival.
This prospective registry study reflected real-life TAVI experience in high-risk elderly patients with aortic stenosis, in whom TAVI appeared to be a reasonable option. (Funded by Edwards Lifesciences and Medtronic.).
The 15
th
European Bifurcation Club (EBC) meeting was held in Barcelona in October 2019. It facilitated a renewed consensus on coronary bifurcation lesions (CBL) and unprotected left main (LM) ...percutaneous interventions. Bifurcation stenting techniques continue to be refined, developed and tested. It remains evident that a provisional approach with optional side branch treatment utilising T, T and small protrusion (TAP) or culotte continues to provide flexible options for the majority of CBL patients. Debate persists regarding the optimal treatment of side branches, including assessment of clinical significance and thresholds for bail-out treatment. In more complex CBL, especially those involving the LM, adoption of dedicated two-stent techniques should be considered. Operators using such techniques have to be fully familiar with their procedural steps and should acknowledge associated limitations and challenges. When using two-stent techniques, failure to perform a final kissing inflation is regarded as a technical failure, since it may jeopardise clinical outcome. The development of novel technical tools and drug regimens deserves attention. In particular, intracoronary imaging, bifurcation simulation, drug-eluting balloon technology and tailored antiplatelet therapy have been identified as promising tools to enhance clinical outcomes. In conclusion, the evolution of a broad spectrum of bifurcation PCI components has resulted from studies extending from bench testing to randomised controlled trials. However, further advances are still needed to achieve the ambitious goal of optimising the clinical outcomes for every patient undergoing PCI on a CBL.
Visual summary
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15th consensus document from the European Bifurcation Club
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Owing to a considerable shift toward bioprosthesis implantation rather than mechanical valves, it is expected that patients will increasingly present with degenerated bioprostheses in the next few ...years. Transcatheter aortic valve-in-valve implantation is a less invasive approach for patients with structural valve deterioration; however, a comprehensive evaluation of survival after the procedure has not yet been performed.
To determine the survival of patients after transcatheter valve-in-valve implantation inside failed surgical bioprosthetic valves.
Correlates for survival were evaluated using a multinational valve-in-valve registry that included 459 patients with degenerated bioprosthetic valves undergoing valve-in-valve implantation between 2007 and May 2013 in 55 centers (mean age, 77.6 SD, 9.8 years; 56% men; median Society of Thoracic Surgeons mortality prediction score, 9.8% interquartile range, 7.7%-16%). Surgical valves were classified as small (≤21 mm; 29.7%), intermediate (>21 and <25 mm; 39.3%), and large (≥25 mm; 31%). Implanted devices included both balloon- and self-expandable valves.
Survival, stroke, and New York Heart Association functional class.
Modes of bioprosthesis failure were stenosis (n = 181 39.4%), regurgitation (n = 139 30.3%), and combined (n = 139 30.3%). The stenosis group had a higher percentage of small valves (37% vs 20.9% and 26.6% in the regurgitation and combined groups, respectively; P = .005). Within 1 month following valve-in-valve implantation, 35 (7.6%) patients died, 8 (1.7%) had major stroke, and 313 (92.6%) of surviving patients had good functional status (New York Heart Association class I/II). The overall 1-year Kaplan-Meier survival rate was 83.2% (95% CI, 80.8%-84.7%; 62 death events; 228 survivors). Patients in the stenosis group had worse 1-year survival (76.6%; 95% CI, 68.9%-83.1%; 34 deaths; 86 survivors) in comparison with the regurgitation group (91.2%; 95% CI, 85.7%-96.7%; 10 deaths; 76 survivors) and the combined group (83.9%; 95% CI, 76.8%-91%; 18 deaths; 66 survivors) (P = .01). Similarly, patients with small valves had worse 1-year survival (74.8% 95% CI, 66.2%-83.4%; 27 deaths; 57 survivors) vs with intermediate-sized valves (81.8%; 95% CI, 75.3%-88.3%; 26 deaths; 92 survivors) and with large valves (93.3%; 95% CI, 85.7%-96.7%; 7 deaths; 73 survivors) (P = .001). Factors associated with mortality within 1 year included having small surgical bioprosthesis (≤21 mm; hazard ratio, 2.04; 95% CI, 1.14-3.67; P = .02) and baseline stenosis (vs regurgitation; hazard ratio, 3.07; 95% CI, 1.33-7.08; P = .008).
In this registry of patients who underwent transcatheter valve-in-valve implantation for degenerated bioprosthetic aortic valves, overall 1-year survival was 83.2%. Survival was lower among patients with small bioprostheses and those with predominant surgical valve stenosis.
The European Bifurcation Club (EBC) was initiated in 2004 to support a continuous overview of the field of coronary artery bifurcation interventions and aims to facilitate a scientific discussion and ...an exchange of ideas on the management of bifurcation disease. The EBC hosts an annual, two-day compact meeting, dedicated to bifurcations, which brings together physicians, pathologists, engineers, biologists, physicists, mathematicians, epidemiologists and statisticians for detailed discussions. Every meeting is finalised with a consensus statement that reflects the unique opportunity of combining the opinion of interventional cardiologists with the opinion of a large variety of other scientists on bifurcation management. A series of consensus sessions dedicated to specific topics, to strengthen the consensus debates and focus the discussions, was introduced at this year's meeting. The sessions comprise an intensive overview of the present literature, a pro and con debate and a voting system, to guide the consensus-building process. The present document represents the summary of the up-to-date EBC consensus and recommendations from the 12th annual EBC meeting in 2016 in Rotterdam.
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