Pitfalls and premature failure of the Freedom SOLO stentless valve.

OBJECTIVES This study reports a series of pitfalls, premature failures and explantations of the third-generation Freedom SOLO (FS) bovine pericardial stentless valve. METHODS A total of 149 patients underwent aortic valve replacement using the FS. Follow-up was 100% complete with an average observation time of 5.5 ± 2.3 years (maximum 8.7 years) and a total of 825 patient-years. Following intraoperative documentation, all explanted valve prostheses underwent histological examination. RESULTS Freedom from structural valve deterioration (SVD) at 5, 6, 7, 8 and 9 years was 92, 88, 80, 70 and 62%, respectively. Fourteen prostheses required explantation due to valve-independent dysfunction (n = 5; i.e. thrombus formation, oversizing, aortic dilatation, endocarditis and suture dehiscence) or valve-dependent failure (acute leaflet tears, n = 4 and severe stenosis, n = 5). Thus, freedom from explantation at 5, 6, 7, 8 and 9 years was 95, 94, 91, 81 and 72%, respectively. An acute vertical tear along the non-coronary/right coronary commissure to the base occurred at a mean of 6.0 years (range 4.3-7.3 years) and affected size 25 and 27 prostheses exclusively. Four FS required explantation after a mean of 7.5 years (range 7.0-8.3 years) due to severe functional stenosis and gross calcification that included the entire aortic root. CONCLUSIONS The FS stentless valve is safe to implant and shows satisfying mid-term results in our single institution experience. Freedom from SVD and explantation decreased markedly after only 6-7 years, so that patients with FS require close observation and follow-up. Exact sizing, symmetric positioning and observing patient limitations are crucial for optimal outcome.

Impaired DNase1-mediated degradation of neutrophil extracellular traps is associated with acute thrombotic microangiopathies.

BACKGROUND Acute thrombotic microangiopathies (TMAs) are characterized by excessive microvascular thrombosis and are associated with markers of neutrophil extracellular traps (NETs) in plasma. NETs are composed of DNA fibers and promote thrombus formation through the activation of platelets and clotting factors. OBJECTIVE The efficient removal of NETs may be required to prevent excessive thrombosis such as in TMAs. To test this hypothesis, we investigated whether TMAs are associated with a defect in the degradation of NETs. APPROACH AND RESULTS We show that NETs generated in vitro were efficiently degraded by plasma from healthy donors. However, NETs remained stable after exposure to plasma from TMA patients. The inability to degrade NETs was linked to a reduced DNase activity in TMA plasma. Plasma DNase1 was required for efficient NET-degradation and TMA plasma showed decreased levels of this enzyme. Supplementation of TMA plasma with recombinant human DNase1 restored NET-degradation activity. CONCLUSIONS Our data indicates that DNase1-mediated degradation of NETs is impaired in patients with TMAs. The role of plasma DNases in thrombosis is, as of yet, poorly understood. Reduced plasma DNase1 activity may cause the persistence of pro-thrombotic NETs and thus promote microvascular thrombosis in TMA patients. This article is protected by copyright. All rights reserved.

Pitfalls and premature failure of the Freedom SOLO stentless valve

Gebiet: Chirurgie Abstract: Objectives This study reports a series of pitfalls, premature failures and explantations of the third generation Freedom SOLO bovine pericardial stentless valve. – – Methods 149 patients underwent aortic valve replacement (AVR) using the FS. Follow-up was 100% complete with an average observation time of 5.5±2.3 years (max. 8.7 years) and a total of 825 patient years. Following intraoperative documentation, all explanted valve prostheses underwent histological examination. – – Results Freedom from structural valve deterioration (SVD) at 5, 6, 7, 8 and 9 years was 92%, 88%, 80% and 70% and 62%, respectively. 14 prostheses required explantation due to valve-independent dysfunction (n=5, i.e. thrombus formation, oversizing, aortic dilatation, endocarditis and suture dehiscence) or valve-dependent failure (acute leaflet tears, n=4, severe stenosis, n=5). Thus freedom from explantation at 5, 6, 7, 8 and 9 years was 95%, 94%, 91% and 81% and 72%, respectively. An acute vertical tear along the non-coronary/right-coronary commissure to the base occurred at a mean of 6.0 years [range 4.3?7.3 years] and affected size 25 and 27 prostheses exclusively. Four FS required explantation after a mean of 7.5 years [range 7.0?8.3 years] due to severe functional stenosis and gross calcification that included the entire aortic root. – – Conclusions The Freedom SOLO stentless valve is safe to implant and shows satisfying mid-term results in our single institution experience. Freedom from SVD and explantation decreased markedly after only 6 ? 7 years, so that patients with FS require close observation and follow-up. Exact sizing, symmetric positioning and observing patient limitations are crucial for optimal outcome.

Failure of fixed orthodontic retainers: A systematic review

OBJECTIVE To evaluate the risk of failure of fixed orthodontic retention protocols. DATA Screening for inclusion eligibility, quality assessment of studies and data extraction was performed independently by two authors. SOURCES The electronic databases MEDLINE, EMBASE and CENTRAL were searched with no restrictions on publication date or language using detailed strategies. The main outcome assessed was bond failure. STUDY SELECTION Twenty-seven studies satisfied the inclusion criteria. Randomised controlled trials and prospective studies were evaluated according to the Cochrane risk of bias tool. Retrospective studies were graded employing the predetermined criteria of Bondemark. RESULTS Nine randomised controlled trials, four of which were of low quality, were identified. Six studies had a prospective design and all were of low quality. Twelve studies were retrospective. The quality of trial reporting was poor in general. Four studies assessing glass-fibre retainers, three RCTs and one prospective, reported bond failures from 11 to 71%, whereas twenty studies evaluating multistranded retainers – nine RCTs, two prospective and nine retrospective – reported failures ranging from 12 to 50%. One comparison was performed, multistranded wires vs. polyehtylene woven ribbon (RR: 1.74; 95% CI: 0.45, 6.73; p=0.42). CONCLUSION The quality of the available evidence is low. No conclusive evidence was found in order to guide orthodontists in the selection of the best protocol. CLINICAL SIGNIFICANCE Although fixed orthodontic retainers have been used for years in clinical practice, the selection of the best treatment protocol still remains a subjective issue. The available studies, and their synthesis, cannot provide reliable evidence in this field.

Regulation of Neutrophil Serine Proteases by Intracellular Serpins

Neutrophil granules contain serine proteases that are central components of the antimicrobial weapons of the innate immune system. Neutrophil proteases also contribute to the amplification and resolution of inflammatory responses through defined proteolytic cleavage of mediators, cell surface receptors, and extracellular matrix proteins. In the blood and at mucosal surfaces, neutrophil serine proteases are regulated by serpins found in plasma and by non-serpin secreted inhibitors. Distinct mechanisms leading to neutrophil cell death have been described for the granule serine proteases, neutrophil elastase, cathepsin G, and proteinase-3. Granule leakage in neutrophils triggers death pathways mediated by cathepsin G and proteinase-3, and both proteases are tightly regulated by their inhibitor SERPINB1 in a cell intrinsic manner. Although stored in the same types of granules, neutrophil elastase does not significantly contribute to cell death following intracellular release from granules into the cytoplasm. However, heterozygous mutations in ELANE, the gene encoding elastase, are the cause of severe congenital neutropenia, a life-threatening condition characterized by the death of neutrophils at an early precursor stage in the bone marrow. This chapter focuses on recent work exploring the biology of clade B intracellular serpins that inhibit neutrophil serine proteases and their functions in neutrophil homeostasis and serine protease control at sites of inflammation.

Influence of Abutment Design on Stiffness, Strength, and Failure of Implant-Supported Monolithic Resin Nano Ceramic (RNC) Crowns

BACKGROUND Recent technical development allows the digital manufacturing of monolithic reconstructions with high-performance materials. For implant-supported crowns, the fixation requires an abutment design onto which the reconstruction can be bonded. PURPOSE The aim of this laboratory investigation was to analyze stiffness, strength, and failure modes of implant-supported, computer-assisted design and computer-aided manufacturing (CAD/CAM)-generated resin nano ceramic (RNC) crowns bonded to three different titanium abutments. MATERIALS AND METHODS Eighteen monolithic RNC crowns were produced and loaded in a universal testing machine under quasi-static condition according to DIN ISO 14801. With regard to the type of titanium abutment, three groups were defined: (1) prefabricated cementable standard; (2) CAD/CAM-constructed individualized; and (3) novel prefabricated bonding base. Stiffness and strength were measured and analyzed statistically with Wilcoxon rank sum test. Sections of the specimens were examined microscopically. RESULTS Stiffness demonstrated high stability for all specimens loaded in the physiological loading range with means and standard deviations of 1,579 ± 120 N/mm (group A), 1,733 ± 89 N/mm (group B), and 1,704 ± 162 N/mm (group C). Mean strength of the novel prefabricated bonding base (group C) was 17% lower than of the two other groups. Plastic deformations were detectable for all implant-abutment crown connections. CONCLUSIONS Monolithic implant crowns made of RNC seem to represent a feasible and stable prosthetic construction under laboratory testing conditions with strength higher than the average occlusal force, independent of the different abutment designs used in this investigation.

Cultural Legacies and Political Preferences: The Failure of Separatism in the Swiss Jura

The study of secession generally stresses the causal influence of cultural identities, political preferences, or ecological factors. Whereas these different views are often considered to be mutually exclusive, this paper proposes a two-stage model in which they are complementary. We posit that cultural identities matter for explaining secessionism, but not because of primordial attachments. Rather, religious and linguistic groups matter because their members are imbued with cultural legacies that lead to distinct political preferences – in this case preferences over welfare statism. Further, ecological constraints such as geography and topography affect social interaction with like-minded individuals. On the basis of both these political preferences and ecological constraints, individuals then make rational choices about the desirability of secession. Instrumental considerations are therefore crucial in explaining the decision to secede, but not in a conventional pocketbook manner. To examine this theory, we analyze the 2013 referendum on the secession of the Jura Bernois region from the Canton of Berne in Switzerland, using municipal level census and referendum data. The results lend support to the theory and suggest one way in which the politics of identity, based on factors like language and religion, can be fused with the politics of interest (preferences for more or less state intervention into the polity and economy) to better understand group behavior.

Computer simulation of electrophoretic aspects of enantiomer migration and separation in capillary electrochromatography with a neutral selector.

A computer simulation study describing the electrophoretic separation and migration of methadone enantiomers in presence of free and immobilized (2-hydroxypropyl)-β-CD is presented. The 1:1 interaction of methadone with the neutral CD was simulated by using experimentally determined mobilities and complexation constants for the complexes in a low-pH BGE comprising phosphoric acid and KOH. The use of complex mobilities represents free solution conditions with the chiral selector being a buffer additive, whereas complex mobilities set to zero provide data that mimic migration and separation with the chiral selector being immobilized, that is CEC conditions in absence of unspecific interaction between analytes and the chiral stationary phase. Simulation data reveal that separations are quicker, electrophoretic displacement rates are reduced, and sensitivity is enhanced in CEC with on-column detection in comparison to free solution conditions. Simulation is used to study electrophoretic analyte behavior at the interface between sample and the CEC column with the chiral selector (analyte stacking) and at the rear end when analytes leave the environment with complexation (analyte destacking). The latter aspect is relevant for off-column analyte detection in CEC and is described here for the first time via the dynamics of migrating analyte zones. Simulation provides insight into means to counteract analyte dilution at the column end via use of a BGE with higher conductivity. Furthermore, the impact of EOF on analyte migration, separation, and detection for configurations with the selector zone being displaced or remaining immobilized under buffer flow is simulated. In all cases, the data reveal that detection should occur within or immediately after the selector zone.

A robust numerical framework for the analysis of material failure of fibre reinforced soft tissue

In this work, robustness and stability of continuum damage models applied to material failure in soft tissues are addressed. In the implicit damage models equipped with softening, the presence of negative eigenvalues in the tangent elemental matrix degrades the condition number of the global matrix, leading to a reduction of the computational performance of the numerical model. Two strategies have been adapted from literature to improve the aforementioned computational performance degradation: the IMPL-EX integration scheme [Oliver,2006], which renders the elemental matrix contribution definite positive, and arclength-type continuation methods [Carrera,1994], which allow to capture the unstable softening branch in brittle ruptures. The IMPL-EX integration scheme has as a major drawback the need to use small time steps to keep numerical error below an acceptable value. A convergence study, limiting the maximum allowed increment of internal variables in the damage model, is presented. Finally, numerical simulation of failure problems with fibre reinforced materials illustrates the performance of the adopted methodology.

A robust numerical framework to the analysis of material failure of fibre reinforced soft tissue

In this work, robustness and stability of continuum damage models applied to material failure in soft tissues are addressed. In the implicit damage models equipped with softening, the presence of negative eigenvalues in the tangent elemental matrix degrades the condition number of the global matrix, leading to a reduction of the computational performance of the numerical model. Two strategies have been adapted from literature to improve the aforementioned computational performance degradation: the IMPL-EX integration scheme [Oliver,2006], which renders the elemental matrix contribution definite positive, and arclength-type continuation methods [Carrera,1994], which allow to capture the unstable softening branch in brittle ruptures. The IMPL-EX integration scheme has as a major drawback the need to use small time steps to keep numerical error below an acceptable value. A convergence study, limiting the maximum allowed increment of internal variables in the damage model, is presented. Finally, numerical simulation of failure problems with fibre reinforced materials illustrates the performance of the adopted methodology.

Statistical characterization of soft tissue inelastic parameters and application to the material failure of the aortic ach

Caracterización de los procesos de disipación mecánica basándose en la microestructura de los tejidos blandos. We present a continuous damage model with regularized softening (smeared crack models) for fiber reinforced soft tissues. Material parameters of the continuous model derive from the mesoscopic scale. In the mesoscopic scale continuum is considered as a collagenous fibrilreinforced composite. We want to study the continnumlevel response as a function of the nanoscale properties of the collagen and the adherent forces between the tropocollagen molecules.

Multiple proportion case-basing driven CBRE and its application in the evaluation of possible failure of firms

Case-based reasoning (CBR) is a unique tool for the evaluation of possible failure of firms (EOPFOF) for its eases of interpretation and implementation. Ensemble computing, a variation of group decision in society, provides a potential means of improving predictive performance of CBR-based EOPFOF. This research aims to integrate bagging and proportion case-basing with CBR to generate a method of proportion bagging CBR for EOPFOF. Diverse multiple case bases are first produced by multiple case-basing, in which a volume parameter is introduced to control the size of each case base. Then, the classic case retrieval algorithm is implemented to generate diverse member CBR predictors. Majority voting, the most frequently used mechanism in ensemble computing, is finally used to aggregate outputs of member CBR predictors in order to produce final prediction of the CBR ensemble. In an empirical experiment, we statistically validated the results of the CBR ensemble from multiple case bases by comparing them with those of multivariate discriminant analysis, logistic regression, classic CBR, the best member CBR predictor and bagging CBR ensemble. The results from Chinese EOPFOF prior to 3 years indicate that the new CBR ensemble, which significantly improved CBRs predictive ability, outperformed all the comparative methods.