Publications

Although the proof of concept of the bioresorbable vascular scaffold (BRS) is well documented, device-related adverse outcomes with first-generation BRS indicate longer-term surveillance. The current study provides insights into the safety and performance of the MeRes100, a novel second-generation sirolimus-eluting BRS, beyond one-year up to three-year follow-up (FU).A total of 108 enrolled patients with de novo coronary artery lesions who underwent implantation of MeRes100 as part of the first-in-human MeRes-1 trial were followed up clinically beyond one year at two and three years and with multiple modality imaging at six months and two years. At three-year FU, the cumulative major adverse cardiac events rate was 1.87%, in the form of two ischaemia-driven target lesion revascularisations. No scaffold thrombosis was reported. Between six months and two years at quantitative coronary angiography, in-segment late lumen loss (LLL) (0.15±0.22 mm vs. 0.23±0.32 mm; p=0.18) and in-scaffold LLL (0.13±0.22 mm vs. 0.24±0.34 mm; p=0.10) changed insignificantly. IVUS subset analysis revealed a non-significant reduction in mean lumen area (6.17±1.28 mm2 vs. 5.47±1.50 mm2; p=0.21) and minimum lumen area (5.14±1.19 mm2 vs. 4.05±1.42 mm2; p=0.10) at two years compared to post-procedural measurements. OCT subset analysis demonstrated 99.24±2.27% neointimal strut coverage.The extended outcomes of the MeRes-1 trial demonstrated sustained efficacy and safety of the MeRes100 BRS with maintained lumen patency up to two years by multimodality imaging and no very late scaffold thrombosis up to three-year clinical FU.The MeRes-1 trial is registered at the Clinical Trials Registry-India. CTRI Number: CTRI/2015/04/005706.

GATA-binding proteins are a subfamily of zinc finger transcription factors with six members (GATA-1-6) that interact with the GATA deoxyribonucleic acid (DNA) sequence. This sequence is found in the regulatory regions of many genes including those encoding T-helper 2 (Th2)-like cytokines, receptors, adhesion molecules and enzymes, which may be important in the pathogenesis of bronchial asthma. The expression of GATA-3, -4 and -6 was investigated in peripheral blood T-lymphocytes and monocytes and bronchial biopsies from 11 normal subjects and 10 steroid-naïve asthmatic patients. Using Western blot analysis, T-cells from asthmatic subjects expressed 5 times the level of GATA-3 compared to that in normals. Confocal microscopy indicated that GATA-3 expression was both nuclear and cytoplasmic. GATA DNA binding complex containing GATA-3 was elevated in Th2 cells as determined by electrophorectic mobility shift assay. In contrast, monocytes from normal and asthmatic subjects expressed GATA-4 and -6 in equal amounts, but no GATA-3 was found. Using immunohistochemistry in bronchial biopsies, epithelial cells expressed high levels of GATA-3, GATA-4 and GATA-6 proteins. Comparison of Western blots of bronchial biopsies showed no significant differences between normal and asthmatic subjects. In conclusion, the increased expression of GATA-3 in asthmatic T-cells may underlie augmented T-helper 2-like cytokines in this disease. However, the unaltered GATA-3 expression in epithelial cells suggests a distinct role for GATA-3 in these cells unrelated to T-helper 2-like cytokine release. Finally, no evidence was found for an increased expression of GATA-4 and GATA-6 in asthma.

The physiology and pathology of the respiratory and gastrointestinal tracts are closely related. This similarity between the two organs may underlie why dysfunction in one organ may induce illness in the other. For example, smoking is a major risk factor for COPD and IBD and increases the risk of developing Crohn’s disease. Probiotics have been defined as “live microorganisms which, when administered in adequate amounts, confer health benefits on the host.” In model systems probiotics regulate innate and inflammatory immune responses. Commonly used probiotics include lactic acid bacteria, particularly Lactobacillus , Bifidobacterium , and Saccharomyces , and these are often used as dietary supplements to provide a health benefit in gastrointestinal diseases including infections, inflammatory bowel disease, and colon cancer. In this respect, probiotics probably act as immunomodulatory agents and activators of host defence pathways which suggest that they could influence disease severity and incidence at sites distal to the gut. There is increasing evidence that orally delivered probiotics are able to regulate immune responses in the respiratory system. This review provides an overview of the possible role of probiotics and their mechanisms of action in the prevention and treatment of respiratory diseases.

This paper addresses the modelling of the static and fatigue behaviour of as-built and machined wire arc additively manufactured (WAAM) steel, with particular focus on the effects of surface undulations, which arise due to process-induced irregularities in heat input, material deposition, and melt pool dynamics. Based on 3D laser scans of WAAM coupons, finite element (FE) models are developed and validated against experimental results obtained using digital image correlation (DIC). The FE method, though accurate, is computationally expensive, since very fine meshes are required to model the as-built undulating surfaces of the WAAM coupons. Therefore, two simplified analytical models, one based on bending and the other on surface curvature, are proposed for the local stress analysis of the WAAM coupons, allowing for the influence of undulating surface and material thickness. The proposed methods are shown to predict the local stresses in the WAAM steel with reasonable accuracy, achieving errors as low as approximately 8–9 %, while maintaining high computational efficiency. The obtained local stresses are further used for the prediction of the fatigue crack initiation location and fatigue life of WAAM steel, achieving good agreement with the experimental results. Two fatigue design classes of FAT 145 and FAT 135 with endurance limits of 270 MPa and 250 MPa, respectively, are derived for WAAM ER70S-6 steel using the proposed models. • Effect of surface undulation as a result of manufacturing process on fatigue is studied. • Numerical simulations of static and fatigue behaviour of WAAM steel are conducted. • Two analytical models are proposed to predict local stresses in WAAM material. • Accuracy of models in fatigue life and crack initiation prediction is demonstrated. • Formation mechanisms of stress concentrations in WAAM material change with thickness.

Objectives. This study was designed to compare the long-term clinical and angiographic effects of successful directional atherectomy and stent implantation and to examine whether restenosis is related to the mechanism of lumen improvement as well as the extent of lumen gain. Background. Directional atherectomy and coronary stent implantation have been shown to achieve a more optimal immediate result that may lead to a more favorable long-term angiographic outcome and fewer target vessel revascularizations than does angioplasty. However, it remains to be determined whether one of the devices used in these interventions provides consistently better results than the other. Methods. To allow meaningful comparisons, a prospectively collected series of 117 patients successfully treated with atherectomy were individually matched with a prospectively collected series of 117 patients successfully treated with stent implantation. Matching for baseline characteristics identified patients with identical lesion location and lesion severity, and immediate and late angiographic and clinical outcome were compared. To evaluate the possibility of a procedure effect on restenosis, patients were further matched for both immediate angiographic outcome and baseline characteristics, providing 150 matched patients for comparison. As confirmatory analysis, multivariate models were constructed to predict late lumen diameter. Results. Matching resulted in two comparable groups with equivalent baseline clinical and stenosis characteristics (n = 117 pairs). Atherectomy led to a smaller immediate gain than stenting and, because late loss was similar in both groups, stenting resulted in a larger late lumen (1.96 ± 0.51 vs.1.66 ± 0.55 mm, p < 0.0001). When patients were matched for immediate gain and baseline characteristics (n = 75 pairs), lumen loss was more pronounced after atherectomy, and thus the minimal lumen diameter at follow-up differed significantly between the two groups (1.66 ± 0.53 vs 1.90 ± 0.47 mm, p = 0.004). This beneficial angiographic effect of stenting was accompanied by a reduced need for repeat interventions. Multivariate analysis confirmed the independent effect of the interventional device used, whereby less loss and greater lumen diameter at follow-up were predicted for stent implantation than for atherectomy. Conclusions. Successful stent implantation provided a more favorable long-term angiographic outcome and lower rates of restenosis and need for target lesion revascularization than did atherectomy. This favorable effect of stenting not only is related to a larger immediate gain, but also seems to attenuate late lumen loss.

To determine the incidence, timing and predictors of periprocedural valve dislodgment with the Medtronic Corevalve System (MCS).Periprocedural valve dislodgment may occur during transcatheter aortic valve implantation (TAVI).Ninety-eight consecutive patients underwent TAVI with the MCS after a comprehensive baseline assessment including invasive angiography, echocardiography, and Multi-Slice Computed Tomography (MSCT). The invasive monitoring charts and angiographic studies of all TAVI procedures were reviewed to determine the incidence and timing of valve dislodgment.Valve dislodgment occurred in 18 patients. Patients with valve dislodgment had a larger Aortic Valve Area (0.76 ± 0.25 cm(2) vs. 0.61 ± 0.19 cm(2) , P = 0.007), lower mean transaortic gradient (37.65 ± 14.62 mm Hg vs. 47.11 ± 16.08 mm Hg, P = 0.03) and significantly less aortic root calcification (Agatston score median 1951 AU (IQR, 799-3103) vs. 3289 AU (IQR 2097-4481), P = 0.016). A lower aortic root calcium score (Agatston score < 2359 AU) was the single independent predictor for valve dislodgment (OR 3.10, 1.09-8.84). After valve dislodgment, the valve could be successfully retrieved and implanted in the proper anatomic location in all cases. Valve dislodgment was associated with a lower incidence of post-procedural AR ≥ 2 (11.1% vs. 34.6%, P = 0.05). There were no relevant procedural or clinical implications to valve dislodgment.The incidence of periprocedural valve dislodgment was 18% in these series. Less aortic root calcification appeared the single independent predictor.

Objectives This study assessed changes in optical coherence tomography (OCT)-defined plaque composition in patients with ST-elevation myocardial infarction (STEMI) receiving high-intensity statin treatment. Background OCT is a high-resolution modality capable of measuring plaque characteristics including fibrous cap thickness (FCT) and macrophage infiltration. There is limited in vivo evidence regarding the effects of statins on OCT-defined coronary atheroma composition and no evidence in the context of STEMI. Methods In the IBIS-4 (Integrated Biomarker Imaging Study-4), 103 patients underwent intravascular ultrasonography and OCT of 2 noninfarct-related coronary arteries in the acute phase of STEMI. Patients were treated with high-dose rosuvastatin for 13 months. Serial OCT imaging was available in 153 arteries from 83 patients. We measured FCT by using a semi-automated method. Co-primary endpoints consisted of the change in minimum FCT (measured in fibroatheromas) and change in macrophage line arc. Results At 13 months, median low-density lipoprotein cholesterol had decreased from 128 mg/dl to 73.6 mg/dl. Minimum FCT, measured in 31 lesions from 27 patients, increased from 64.9 ± 19.9 μm to 87.9 ± 38.1 μm (p = 0.008). Macrophage line arc decreased from 9.6° ± 12.8° to 6.4° ± 9.6° (p < 0.0001). The secondary endpoint, mean lipid arc, decreased from 55.9° ± 37° to 43.5° ± 33.5°. In lesion-level analyses (n = 191), 9 of 13 thin-cap fibroatheromata (TCFAs) at baseline (69.2%) regressed to non-TCFA morphology, whereas 2 of 178 non-TCFA lesions (1.1%) progressed to TCFAs. Conclusions In this observational study, we found significant increase in minimum FCT, reduction in macrophage accumulation, and frequent regression of TCFAs to other plaque phenotypes in nonculprit lesions of patients with STEMI treated with high-intensity statin therapy.

Background The pathophysiological pattern of coronary artery disease (CAD) pre-procedure may affect the physiological response to percutaneous coronary intervention (PCI). Purpose The aim of this study was to evaluate whether the pathophysiological pattern of CAD, derived from virtual pullbacks of angiography-based fractional flow reserve, was predictive of the immediate hemodynamic outcome post-PCI. Methods Data from 206 patients with chronic coronary syndrome enrolled in the ASET (Acetyl Salicylic Elimination Trial) JAPAN study were analyzed. The ASET JAPAN study is a multi-center, single-arm, open-label, proof-of-concept trial to demonstrate the feasibility and safety of "aspirin-free" therapy with low-dose prasugrel (3.75 mg) monotherapy following PCI, Pre-procedural pathophysiological patterns in CAD were characterized by the physiological distribution and local severity of coronary atherosclerosis using Murray law-based quantitative flow ratio (µQFR)-derived indexes acquired from pre-PCI angiograms. The physiological distribution of CAD was defined as "predominant diffuse" or "focal" according to a µQFR pullback pressure gradient (PPG) index &amp;lt;0.78 or ≥0.78, respectively. Physiological local severity was assessed using µQFR gradient per 1 mm (dµQFR/ds), with a value ≥ 0.025/mm defining the presence of a "major gradient". The statistical association of preprocedural pathophysiological pattern of CAD with post-PCI µQFR &amp;lt;0.91 was investigated. Results Out of 207 vessels, 26.6% (n=55) were classified as predominantly focal (µQFR PPG index ≥0.78) with a major gradient (dµQFR/ds ≥0.025/mm, Group 1), 1.0% (n=2) predominantly focal without a major gradient (Group 2), 53.6% (n=111) predominantly diffuse (µQFR PPG index &amp;lt;0.78) with a major gradient (Group 3), and 18.8% (n=39) predominantly diffuse with no major gradient (Group 4)(Figure 1). Vessels with predominantly diffuse disease and no major gradient (Group 4) had significantly higher pre-PCI µQFR (mean difference, -0.163; 95%CI, -0.211 to -0.118) and lower post-PCI µQFR (mean difference, 0.031; 95% CI, 0.014 to 0.487; by bootstrapping using 2000 replications) than those with predominantly focal disease and major gradients (Group 1). Low pre-PCI µQFR values were significantly associated with an increased risk of a post-PCI µQFR &amp;lt;0.91 (Figure 2A). Similarly, low µQFR PPG index showed a significantly higher risk of a post-PCI µQFR &amp;lt;0.91 (Figure 2B). The highest dµQFR/ds had no significant impact on the risk of a post-PCI µQFR &amp;lt;0.91 (Figure 2C). In multivariable analysis, low µQFR PPG index (diffuse disease) was an independent factor for predicting a post-PCI µQFR &amp;lt;0.91 (per 0.1 decrease of µQFR PPG index, OR:1.68, 95% CI 1.17-2.46, p=0.005). Conclusions A physiological pattern of diffuse CAD pre-procedure was an independent factor in predicting an unfavorable immediate hemodynamic outcome post-PCI.