Randomized comparison of biodegradable polymer sirolimus-eluting stents versus durable polymer everolimus-eluting stents for percutaneous coronary revascularization: Rationale and design of the BIOSCIENCE trial

Background Biodegradable polymers for release of antiproliferative drugs from metallic drug-eluting stents (DES) aim to improve long-term vascular healing and efficacy. We designed a large scale clinical trial to compare a novel thin strut, cobalt chromium DES with silicon carbide coating releasing sirolimus from a biodegradable polymer (Orsiro, O-SES) with the durable polymer-based Xience Prime everolimus-eluting stent (X-EES) in an all-comers patient population. Design The multicenter BIOSCIENCE trial (NCT01443104) randomly assigned 2,119 patients to treatment with biodegradable polymer SES or durable polymer EES at 9 sites in Switzerland. Patients with chronic stable coronary artery disease or acute coronary syndromes, including non-ST-elevation and ST-elevation myocardial infarction, were eligible for the trial if they had at least one lesion with a diameter stenosis >50% appropriate for coronary stent implantation. The primary endpoint target lesion failure (TLF) is a composite of cardiac death, target-vessel myocardial infarction, and clinically-driven target lesion revascularization within 12 months. Assuming a TLF rate of 8% at 12 months in both treatment arms and accepting 3.5% as a margin for non-inferiority, inclusion of 2,060 patients would provide 80% power to detect non-inferiority of the biodegradable polymer SES compared with the durable polymer EES at a one-sided type I error of 0.05. Clinical follow-up will be continued through five years. Conclusion The BIOSCIENCE trial will determine whether the biodegradable polymer SES is non-inferior to the durable polymer EES with respect to TLF.

Serotype epidemiology of invasive pneumococcal disease in Swiss adults: A nationwide population-based study.

BACKGROUND In Switzerland, the heptavalent (PCV7) and 13-valent pneumococcal conjugate vaccine (PCV13) were recommended for all infants aged <2 years in 2007 and 2011, respectively. Due to herd effects, a protective impact on the invasive pneumococcal disease (IPD) rates in adults had been expected. METHODS Within this study, data from the nationwide mandatory surveillance was analyzed for all adult patients ≥16 years with IPD of known serotype/serogroup during 2003-2012. Trend (for IPD cases from 2003 to 2012) and logistic regression analyses (2007-2010) were performed to identify changes in serotype distribution and to identify the association of serotypes with age, clinical manifestations, comorbidities and case fatality, respectively. FINDINGS The proportion of PCV7 serotypes among all IPD cases (n=7678) significantly declined in adults from 44.7% (2003) before to 16.7% (2012) after the recommendation of PCV7 (P<0.001). In contrast, the proportion of non-PCV7 serogroup/serotypes increased for non-PCV13 but also PCV13 serotypes (not included in PCV7) at the same time. Serotype distribution varied significantly across ages, clinical manifestations and comorbidities. Serotype was furthermore associated with case fatality (P=0.001). In a multivariable logistic regression model, analyzing single serotypes showed that case-fatality was increased for the serotypes 3 (P=0.008), 19A (P=0.03) and 19F (P=0.005), compared to serotype 1 and 7F. CONCLUSION There was a significant decline in PCV7 serotypes among adults with IPD in Switzerland after introduction of childhood vaccination with PCV7. Pneumococcal serotypes were associated with case fatality, age, clinical manifestation and comorbidities of IPD in adults. These results may prove useful for future vaccine recommendations for adults in Switzerland.

The Freedom SOLO bovine pericardial stentless valve: Single-center experience, outcome and long-term durability

Abstract Objectives We report our institutional experience and long-term results with the Sorin Freedom SOLO bovine pericardial stentless bioprosthesis. Methods Between January 2005 and November 2009, 149 patients (mean age 73.6±8.7 years, 68 [45.6%] female) underwent isolated (n=75) or combined (n=74) aortic valve replacement (AVR) using the SOLO in our institution. Follow-up was 100% complete with an average follow-up time of 5.9±2.6 years (maximum 9.6 years) and a total of 885.3 patient years. Results Operative (30-day) mortality was 2.7% (1.3% for isolated AVR [n=1] and 4.0% for combined procedures [n=3]). All causes of death were not valve-related. Preoperative peak (mean) gradients of 74.2±23.0 mmHg (48.6 ± 16.3 mmHg) decreased to 15.6±5.4 (8.8±3.0) after AVR, and remained low for up to 9 years. The postoperative effective orifice area (EOA) was 1.6 ±0.57 cm2, 1.90±0.45 cm2, 2.12±0.48 cm2 and 2.20±0.66 cm2 for the valve sizes 21, 23, 25 and 27, respectively; with absence of severe prosthesis-patient-mismatch (PPM) and 0.7% (n=1) moderate PPM. During follow-up, Twenty-six patients experienced structural valve deterioration (SVD) and 14 patients underwent explantation. Kaplan-Meier estimates for freedom from death, explantation and SVD at 9 years averaged 0.57 [0.47‒0.66], 0.82 [0.69‒0.90] and 0.70 [0.57‒0.79], respectively. Conclusions The Freedom SOLO stentless aortic valve is safe to implant and shows excellent early and mid-term hemodynamic performance. However, SVD was observed in a substantial number of patients after only 5 ̶ 6 years and the need for explantation increased markedly, suggesting low durability.

Komatiites constrain molybdenum isotope composition of the Earth's mantle

In order to estimate the Mo isotope composition and Mo abundance in the Bulk Silicate Earth (BSE), a total of thirty komatiite samples from five localities on three continents were analyzed using an isotope dilution double spike technique. Calculated Mo concentrations of the emplaced komatiite lavas range from 25±325±3 to 66±22 ng/g66±22 ng/g, and the inferred Mo concentrations in the deep mantle sources of the komatiites range between 17±417±4 and 30±12 ng/g30±12 ng/g, with an average value of 23±7 ng/g23±7 ng/g (2SE). This average value represents our best estimate for the Mo concentration in the BSE; it is identical, within the uncertainty, to published previous estimates of 39±16 ng/g39±16 ng/g, but is at least a factor of 2 more precise. The Mo isotope compositions of the komatiite mantle sources overlap within uncertainty and range from View the MathML sourceδMo98=−0.04±0.28 to 0.11±0.10‰0.11±0.10‰, with an average of 0.04±0.06‰0.04±0.06‰ (2SE). This value is analytically indistinguishable from published Mo isotope compositions of ordinary and enstatite chondrites and represents the best estimate for the Mo isotope composition of the BSE. The inferred δ98Mo for the BSE is therefore lighter than the suggested average of the upper continental crust (0.3 to 0.4‰). Thus, from the mass balance standpoint, a reservoir with lighter Mo isotope composition should exist in the Earth's mantle; this reservoir can potentially be found in subducted oceanic crust. The similarity of δ98Mo between chondritic meteorites and estimates for the BSE from this study indicates that during the last major equilibration between Earth's core and mantle, i.e., the one that occurred during the giant impact that produced the Moon, chemical and isotopic equilibrium of Mo between Fe metal of the core and the silicate mantle was largely achieved.

Fluid-related inclusions in Alpine high-pressure peridotite reveal trace element recycling during subduction-zone dehydration of serpentinized mantle (Cima di Gagnone, Swiss Alps).

Serpentinites release at sub-arc depths volatiles and several fluid-mobile trace elements found in arc magmas. Constraining element uptake in these rocks and defining the trace element composition of fluids released upon serpentinite dehydration can improve our understanding of mass transfer across subduction zones and to volcanic arcs. The eclogite-facies garnet metaperidotite and chlorite harzburgite bodies embedded in paragneiss of the subduction melange from Cima di Gagnone derive from serpentinized peridotite protoliths and are unique examples of ultramafic rocks that experienced subduction metasomatism and devolatilization. In these rocks, metamorphic olivine and garnet trap polyphase inclusions representing the fluid released during high-pressure breakdown of antigorite and chlorite. Combining major element mapping and laser-ablation ICP-MS bulk inclusion analysis, we characterize the mineral content of polyphase inclusions and quantify the fluid composition. Silicates, Cl-bearing phases, sulphides, carbonates, and oxides document post-entrapment mineral growth in the inclusions starting immediately after fluid entrapment. Compositional data reveal the presence of two different fluid types. The first (type A) records a fluid prominently enriched in fluid-mobile elements, with Cl, Cs, Pb, As, Sb concentrations up to 10(3) PM (primitive mantle), similar to 10(2) PM Tit Ba, while Rb, B, Sr, Li, U concentrations are of the order of 10(1) PM, and alkalis are similar to 2 PM. The second fluid (type B) has considerably lower fluid-mobile element enrichments, but its enrichment patterns are comparable to type A fluid. Our data reveal multistage fluid uptake in these peridotite bodies, including selective element enrichment during seafloor alteration, followed by fluid-rock interaction along with subduction metamorphism in the plate interface melange. Here, infiltration of sediment-equilibrated fluid produced significant enrichment of the serpentinites in As, Sb, B, Pb, an enriched trace element pattern that was then transferred to the fluid released at greater depth upon serpentine dehydration (type A fluid). The type B fluid hosted by garnet may record the composition of the chlorite breakdown fluid released at even greater depth. The Gagnone study-case demonstrates that serpentinized peridotites acquire water and fluid-mobile elements during ocean floor hydration and through exchange with sediment-equilibrated fluids in the early subduction stages. Subsequent antigorite devolatilization at subarc depths delivers aqueous fluids to the mantle wedge that can be prominently enriched in sediment-derived components, potentially triggering arc magmatism without the need of concomitant dehydration/melting of metasediments or altered oceanic crust.