Publications

Background: Balloon post-dilatation (BPD) is often needed for optimizing transcatheter heart valve (THV) implantation, since paravalvular leak (PVL) after transcatheter aortic valve implantation is associated with poor outcome and mortality. Quantitative assessment of PVL severity before and after BPD is mandatory to properly assess PVL, thus improving implantation results and outcomes. Objective: To investigate a quantitative angiographic assessment of aortic regurgitation (AR) by videodensitometry before and after BPD. Methods: Videodensitometric-AR assessments (VD-AR) before and after BPD were analysed in 61 cases. Results: VD-AR decreased significantly from 24.0[18.0-30.5]% to 12.0[5.5-19.0]% (p < 0.001, a two-tailed p < 0.05 defined the statistical significance). The relative delta of VD-AR after BPD ranged from -100% (improvement) to +40% (deterioration) and its median value was -46.2%. The frequency of improvement, no change, and deterioration were 70% (n = 43), 25% (n = 15) and 5% (n = 3), respectively. Significant AR (VD-AR > 17%) was observed in 47 patients (77%) before and in 19 patients (31%) after BPD. Conclusions: VD-AR after THV implantation provides a quantitative assessment of post-TAVI regurgitation and can help in the decision-making process on performing BPD and in determining its efficacy.

The objective of this preclinical study was to evaluate the feasibility and safety of transcatheter endocardial alginate hydrogel injection (TEAi) in a large animal model, utilizing the high-stiffness XDROP® alginate hydrogel in combination with the dedicated EndoWings® catheter-based system. All swine ( n = 9) successfully underwent TEAi without complications. Acute results from a subset of animals ( n = 5) demonstrated the ability of the catheter to access a wide range of endomyocardial areas and achieve consecutive circumferential hydrogel distribution patterns within the mid-left ventricular wall. Histological examinations at 6 months ( n = 4) demonstrated that the XDROP® remained localized within the cardiac tissue. In addition, serial echocardiographic imaging showed that XDROP® had no adverse impacts on LV systolic and diastolic functions. In conclusion, this innovative combination technology has the potential to overcome the translational barriers related to alginate hydrogel delivery to the myocardium. Graphical abstract

The aim of the study was to evaluate the effect of strut protrusion (SP) on wall shear stress (WSS) and neointimal growth (NG) one and five years after implantation of an Absorb bioresorbable vascular scaffold.Eight patients were selected from a first-in-man study. Following three-dimensional (3D) reconstruction of coronaries, WSS was quantified using Newtonian steady-flow simulation in each cross-section at 5° subunits (sectors) of the circumferential luminal surface. At one year, neointimal thickness (NT) was measured by optical coherence tomography (OCT) and correlated to WSS and SP post procedure. Median SP was 112.9 (90.8, 133.1) µm post implantation. Post procedure, a logarithmic inverse relationship between SP and post-implantation WSS (r=-0.425, p<0.001; correlation coefficients in a range from -0.143 to -0.553) was observed, whereas a correlation between baseline logarithm-transformed WSS (log-WSS) and NT (r=-0.451, p<0.001; correlation coefficients ranged from -0.140 to -0.662) was documented at one year. Mixed-effects analysis between baseline log-WSS and NT at follow-up yielded a slope of 30 µm/ln Pascal (Pa) and a y-intercept of 98 µm. As a result of NG, median flow area decreased from 6.91 (6.53, 7.48) mm2 post implantation to 5.65 (5.47, 6.02) mm2 at one-year follow-up (p=0.01) and to 5.75±1.37 mm2 at five-year follow-up (p=0.024). However, the vessel surface exposed to low WSS (<1 Pa) decreased significantly post procedure (42%) to one year (35.9%) and five years (15.2%) (p-overall <0.0001).SP disturbs laminar flow, creates regions of low WSS (<1.0 Pa) that are associated with NG and lumen area reduction. Low WSS post implantation reduced significantly at long-term follow-up. Thin struts with effective embedment would substantially reduce NG and accelerate homogenisation of WSS towards physiological values.

Over 5.4 million adults receive treatment for asthma in the UK. Asthma is a chronic allergic disorder characterised by chronic inflammation. Type 2 T helper (T H 2) are an important component in the development of the asthma and the response to allergens, producing the cytokines interleukin (IL) -4 and IL-13. In T H 2 cells, production of the cytokines IL-4, IL-5, and IL-13 in a co-ordinate manner. Th2 cytokine expression is controlled by cooperation between transcription factors GATA-3 and Nuclear factor of activated T-cells -1 (NFAT1). The genes encoding these cytokines are located together the same chromosomal region, 5q31.1 in humans. We have investigated the co-ordinated expression of IL4 and IL13 in the T H 2 model cell line HUT78. Using chromatin immunoprecipitation (ChIP) and re-ChIP analysis we have shown that in HUT78 cells GATA-3 is associated with the IL4 and IL13 promoter regions. Additionally, following stimulation CD3/28 antibodies NFAT1 rapidly translocates to the nucleus and becomes associated with the promoter regions and GATA3. Finally, using Chromatin Conformation Capture (3C) we demonstrate looping of DNA at the IL4 and IL13 promoters to bring them into close proximity with each other. This suggests that the formation of a transcriptional hub under the control of GATA-3 and NF-AT drives co-ordinate T H 2 cytokine production.

<h3>Introduction:</h3> COPD is associated with cellular senescence, hallmarks of which include increased cell size, autofluorescence, senescence associated-β-galactosidase (SA-β-Gal) staining, mitochondrial dysfunction, reduced proliferation and cell cycle inhibitor expression. Dilution of these markers due to proliferation of non-senescent cells makes studying senescence in proliferative cells, such as fibroblasts, challenging. <h3>Aim:</h3> Assess whether senescent fibroblasts can be isolated from a mixed COPD fibroblast population. <h3>Method:</h3> Fibroblasts were isolated from COPD patient lung resections (n=6). Cells were sorted using a FACSAria Fusion into a "senescence-enriched population" (largest and most autofluorescence) and a "non-senescent population" (smallest, least autofluorescence). Senescence was investigated in these populations using SA-β-Gal for senescent cell identification, iCELLigence technology to assess proliferation, Seahorse assay to investigate mitochondrial function and RT-qPCR to measure cell cycle inhibitor expression. <h3>Results:</h3> Senescence-enriched fibroblasts were larger and more autofluorescence and displayed greater SA-β-Gal staining. These cells trended towards reduced proliferation over the first 48h of growth compared to the non-senescent population. Senescence-enriched fibroblasts showed increased basal mitochondrial function (p&lt;0.05), maximal respiration (p&lt;0.05) and ATP production (p=0.06). Senescence-enriched fibroblasts also exhibited elevated p16^INK4a (p&lt;0.05), p21^WAF1/CIP1 (p&lt;0.05) and p15^INK4b (p=0.10) gene expression. <h3>Conclusion:</h3> These data suggest FACS isolate senescent-enriched fibroblasts. This technique can be used to study fibroblast senescence mechanisms and provide therapeutic targets for COPD.

No abstract is provided for this article.

The SYNTAX study compared PCI with TAXUS Express stents to CABG for the treatment of de novo 3-vessel and/or left main coronary disease. This study aimed to determine patient characteristics and five-year outcomes after a staged PCI strategy compared to single-session PCI.In the SYNTAX trial, staged procedures were discouraged but were allowed within 72 hours or, if renal insufficiency or contrast-induced nephropathy occurred, within 14 days (mean 9.8±18.1 days post initial procedure). A total of 125 (14%) patients underwent staged PCI. These patients had greater disease severity and/or required a more complex procedure. MACCE was significantly increased in staged patients (48.1% vs. 35.5%, p=0.004), as was the composite of death/stroke/MI (32.2% vs. 19%, p=0.0007). Individually, cardiac death and stroke occurred more frequently in the staged PCI group (p=0.03). Repeat revascularisation was significantly higher in staged patients (32.8% vs 24.8%, p=0.035), as was stent thrombosis (10.9% vs. 4.7%, p=0.005).There is a higher incidence of MACCE in patients undergoing staged compared to single-session PCI for 3-vessel and/or left main disease over the first five years of follow-up. However, these patients had more comorbidities and more diffuse disease.

Abstract In the framework of the revision of Eurocode 3, Part 1–1, several amendments have been proposed and accepted in order to improve the rules for the resistance to member buckling. For clarification, a flow chart connecting the global analysis (first or second order), the imperfections and the type of verification has been implemented for ease of use. Since the publication of the standard in 2005, many research projects have been conducted across Europe on this topic and their results have contributed to provide appropriate answers to problems identified in practice. Therefore, the revised code provides new design rules for stability. Important works of calibration have been performed in these different projects to derive appropriate values of the partial factor on the resistance side. For example, a new formulation for lateral–torsional buckling has been introduced for the calculation of the reduction factor. The consequence is a reduction of the discrepancy between the results obtained by these new methods and those from experimental or numerical tests. In order to extend the scope of Eurocode 3, Part 1–1, additional methods have been implemented in an annex to cover the stability of members with mono‐symmetric cross‐section under compression axial force, biaxial bending, with or without torsion. The format of the resistance criteria remains similar to the format of the current interaction formulae so that the designers can easily identify the evolution of the rules. This article presents in a systematic way the new implementations in the formal vote version FprEN 1993‐1‐1 of the code.