Design, manufacturing and testing of a green non-isocyanate polyurethane prosthetic heart valve.

peer reviewedThe sole effective treatment for most patients with heart valve disease is valve replacement by implantation of mechanical or biological prostheses. However, mechanical valves represent high risk of thromboembolism, and biological prostheses are prone to early degeneration. In this work, we aim to determine the potential of novel environmentally-friendly non-isocyanate polyurethanes (NIPUs) for manufacturing synthetic prosthetic heart valves. Polyhydroxyurethane (PHU) NIPUs are synthesized via an isocyanate-free route, tested in vitro, and used to produce aortic valves. PHU elastomers reinforced with a polyester mesh show mechanical properties similar to native valve leaflets. These NIPUs do not cause hemolysis. Interestingly, both platelet adhesion and contact activation-induced coagulation are strongly reduced on NIPU surfaces, indicating low thrombogenicity. Fibroblasts and endothelial cells maintain normal growth and shape after indirect contact with NIPUs. Fluid-structure interaction (FSI) allows modeling of the ideal valve design, with minimal shear stress on the leaflets. Injection-molded valves are tested in a pulse duplicator and show ISO-compliant hydrodynamic performance, comparable to clinically-used bioprostheses. Poly(tetrahydrofuran) (PTHF)-NIPU patches do not show any evidence of calcification over a period of 8 weeks. NIPUs are promising sustainable biomaterials for the manufacturing of improved prosthetic valves with low thrombogenicity

Does Speciation between Arabidopsis halleri and Arabidopsis lyrata Coincide with Major Changes in a Molecular Target of Adaptation?

Ever since Darwin proposed natural selection as the driving force for the origin of species, the role of adaptive processes in speciation has remained controversial. In particular, a largely unsolved issue is whether key divergent ecological adaptations are associated with speciation events or evolve secondarily within sister species after the split. The plant Arabidopsis halleri is one of the few species able to colonize soils highly enriched in zinc and cadmium. Recent advances in the molecular genetics of adaptation show that the physiology of this derived ecological trait involves copy number expansions of the AhHMA4 gene, for which orthologs are found in single copy in the closely related A. lyrata and the outgroup A. thaliana. To gain insight into the speciation process, we ask whether adaptive molecular changes at this candidate gene were contemporary with important stages of the speciation process. We first inferred the scenario and timescale of speciation by comparing patterns of variation across the genomic backgrounds of A. halleri and A. lyrata. Then, we estimated the timing of the first duplication of AhHMA4 in A. halleri. Our analysis suggests that the historical split between the two species closely coincides with major changes in this molecular target of adaptation in the A. halleri lineage. These results clearly indicate that these changes evolved in A. halleri well before industrial activities fostered the spread of Zn- and Cd-polluted areas, and suggest that adaptive processes related to heavy-metal homeostasis played a major role in the speciation process

Long-term volumetric analysis of vestibular schwannomas following stereotactic radiotherapy: Practical implications for follow-up.

Transient tumor swelling is a well-known phenomenon following radiotherapy for vestibular schwannomas (VS). We analyzed the long-term volumetric changes of VS after LINAC radiosurgery, in order to determine a time interval during which a true tumor progression can be distinguished from a pseudoprogression. Among 63 patients with VS treated by one fraction or fractionated radiotherapy, we selected 52 of them who had a minimal follow-up of 5 years. Maximal axial diameter and three-dimensional tumor volume were measured on each MRI scan. Volume changes were interpreted using different error margins ranging from 10 to 20%. Patients were categorized according to the tumor evolution pattern over time. Median follow-up was 83 months. One tumor (1.9%) remained stable and 26.9% had continuous shrinkage. Applying an error margin of 13%, a transient tumor enlargement was observed in 63.5% of patients, with a first peak at 6-12 months and a late peak at 3-4 years. A true progression was suspected in 4 (7.7%) patients, tumor regrowth starting after the 3rd or 4th year post-treatment. Only one patient required salvage radiotherapy. Transient swelling of VS following radiotherapy is generally an early phenomenon but may occur late. In the first 5 years, a true tumor progression cannot be differentiated from a pseudoprogression. A significant tumor expansion observed on 3 sequential MRI scans after the 3rd year may be suggestive of treatment failure. Long-term follow-up is therefore mandatory and no decision of salvage treatment should be made until the 6th year

Effect of neuro-orthopaedic surgery for spastic equinovarus foot after stroke. A prospective longitudinal study based on a goal-centered approach.

Neuro-orthopaedic surgery is recognized as an effective treatment to improve walking capacity in case of spastic equinovarus foot. However, the effect of surgery on the 3 domains of the International Classification of Functioning, Disability and Health (ICF) has never been studied. To assess the efficacy of the neuro-orthopaedic surgery for spastic equinovarus foot after stroke based on a goal-centered approach and on the 3 domains of the International Classification of Functioning, Disability and Health (ICF). Prospective, single blind, case-series, intervention study (before-after trial) with a 1-year follow-up. Eighteen hemiplegic patients with spastic equinovarus foot. A selective tibial neurotomy and/or an Achille tendon lengthening and/or a tibialis anterior tendon transfer were performed to correct a disabling SEF. The primary outcome measure was the goal attainment scale. The secondary outcome measures included body function and structure (spasticity, strength, range of motion, pain, gait speed, ankle kinematics), activities (walking aids, functional ambulation category, functional walking category, ABILOCO) and social participation and quality of life (Satispart-Stroke, SF-36) assessment before and 2 months and 1 year after surgery. An increase in the goal attainment scale score, in the body function and activity/participation domains of the ICF, a decrease in triceps spasticity and pain, an increase in ankle range of motion and gait speed, an improvement in equinus and a reduction in walking aids were observed. This study confirms the efficacy of the neuro-orthopaedic surgical treatment of spastic equinovarus foot after stroke to improve walking capacities and to achieve personal goals in the body function and activity/participation domains of the ICF

Platelets and aortic valve calcification: insights from a rabbit model and from patients with severe aortic stenosis

Background Calcific aortic stenosis (CAS) is the most frequent valvular heart disease in industrialized countries. CAS is characterized by progressive aortic valve remodelling and calcification, which leads to valvular dysfunction and subsequent cardiac impairment. The extent of aortic valve calcification accurately predicts AS severity and prognosis. A recent preclinical study proposed a role for activated platelets in valvular calcification through transforming growth factor-b (TGF-b) or autotaxin-lysophosphatidic acid (LPA). Platelet parameters may therefore represent new circulating biomarkers of CAS progression and outcome. Aim To perform a longitudinal analysis of platelet markers in a new rabbit model of aorta and aortic valve calcification and study their correlation with aortic valve calcium score in patients with severe AS. Methods Twelve-week old male New Zealand White rabbits were fed for 16 weeks (W) with a palm oil-enriched diet (5% palm oil) supplemented with vitamin D2 (25.000U/day/2.5kg) during the first two weeks. Computed tomography (CT) was performed at baseline, W4, W8, W12 and W16 to analyze the appearance of macrocalcifications. Blood samples were collected at the same time points to study the evolution of platelet count. ADP closure time (CT-ADP) was measured in whole blood on a PFA-200. After 16 weeks, the heart and the aorta were collected and fixed for histological analyses of tissue structure (hematoxylin-eosin staining) and calcification (alizarin red staining). In parallel, platelet count, number of activated platelets (CD62P+), CT-ADP, plasma levels of autotaxin, LPA and TGF-b, and CT aortic valve calcium score (CT-AVC) were studied in 36 patients with severe AS undergoing transcatheter aortic valve replacement implantation (TAVI). Results After 16 weeks, all rabbits fed with the palm-oil enriched diet exhibited massive aortic wall calcification, characterized by the presence of large calcification nodules in the aortic media. These aortic macrocalcifications were detectable in vivo by CT in 5 rabbits out of 6. Calcification nodules were also detected in the aortic valve fibrosa of 2 rabbits out of 6 via histological alizarin red staining of explanted hearts. Platelet count decreased as early as after 8 weeks of diet (489 K/μl vs 373K/μl, P<0.05) and kept decreasing progressively along with calcification development. No changes in CT-ADP values were observed over time. In AS patients, as expected, CT-AVC correlated well with peak aortic jet velocity (r=0.49, P=0.0054). Interestingly, CT-AVC was inversely correlated to platelet count (r=-0.52, P=0.0012) and to the number of circulating CD62P+ platelets (r=-0.45, P=0.0073). Although CT-ADP values were above normal values for AS patients, CT-ADP did not correlate with CTAVC. Finally, in agreement with a role for activated platelets as a major source of TGF-b, levels of this cytokine showed good correlation with the number of CD62P+ platelets (r=0.46, P=0.0053). Conclusions Platelet consumption is associated with aortic valve calcification both in our rabbit model and in AS patients. These findings support a role for platelets in this process, possibly via TGF-b. Hence, platelet count might help assessing AS severity and provide prognostic information. This warrants further investigations

Neutrophil Phenotypes in Coronary Artery Disease.

Clinical evidence indicates that innate immune cells may contribute to acute coronary syndrome (ACS). Our prospective study aimed at investigating the association of neutrophil phenotypes with ACS. 108 patients were categorized into chronic stable coronary artery disease (n = 37), unstable angina (UA) (n = 19), Non-ST-Elevation Myocardial Infarction (NSTEMI) (n = 25), and ST-Elevation Myocardial Infarction (STEMI) (n = 27). At the time of inclusion, blood neutrophil subpopulations were analysed by flow cytometry. Differential blood cell count and plasma levels of neutrophilic soluble markers were recorded at admission and, for half of patients, at six-month follow-up. STEMI and NSTEMI patients displayed higher neutrophil count and neutrophil-to-lymphocyte ratio than stable and UA patients (p < 0.0001), which normalized at six-month post-MI. Atypical low-density neutrophils were detected in the blood of the four patient groups. STEMI patients were characterized by elevated percentages of band cells compared to the other patients (p = 0.019). Multivariable logistic regression analysis revealed that plasma levels of total myeloperoxidase was associated with STEMI compared to stable (OR: 1.434; 95% CI: 1.119-1.837; P < 0.0001), UA (1.47; 1.146-1.886; p = 0.002), and NSTEMI (1.213; 1.1-1.134; p = 0.0001) patients, while increased neutrophil side scatter (SSC) signal intensity was associated with NSTEMI compared to stable patients (3.828; 1.033-14.184; p = 0.045). Hence, changes in neutrophil phenotype are concomitant to ACS

Platelet-rich plasma (PRP) and tendon healing: comparison between fresh and frozen-thawed PRP

Platelet-rich plasma (PRP) is increasingly used in the treatment of musculoskeletal diseases. Its preservation by freezing it for the realization of multiple injections in clinical use has never been discussed. Calcaneal tendons of rats were surgically sectioned. Platelet concentration of the PRP was 2.5 x 106/μl with autologous plasma of rats. Frozen-thawed PRP was prepared by performing two cycles of freezing and thawing on PRP aliquots. Both platelet preparations were injected in the lesion. Biomechanical and histological evaluations were carried out after 7, 20 or 40 days post surgery. After 7 and 40 days, no significant difference was observed between the PRP and the frozen-thawed PRP group. There is however a difference 20 days after surgery: the ultimate tensile strength (UTS) was greater in the fresh PRP group. No obvious difference with histological aspect was observed between the two groups. In conclusion, fresh PRP and frozen-thawed PRP injections can lead to similar results in the healing process of section calcaneal tendons of rats. Improvements with fresh PRP are slight. PRP could thus be frozen to be preserved if multiple injections are needed (e.g. osteoarthritis)