Publications

Little is known about the elastic behavior of the coronary vessel wall directly after percutaneous transluminal coronary angioplasty (PTCA). Minimal luminal cross-sectional areas of 151 successfully dilated lesions were studied in 136 patients during balloon inflation and directly after withdrawal of the balloon. To circumvent geometric assumptions about the shape of the stenosis after PTCA, a videodensitometric analysis technique was used for the assessment of vascular cross-sectional areas. Elastic recoil was defined as the difference between balloon cross-sectional area of the largest balloon used at the highest pressure and minimal luminal cross-sectional area after PTCA. Mean balloon cross-sectional area was 5.2 ± 1.6 mm2 with a mean minimal cross-sectional area of 2.8 ± 1.4 mm2 immediately after inflation. Oversizing of the balloon (balloon artery ratio >1) led to more recoil (0.8 ± 0.3 vs 0.6 ± 0.3 mm, p < 0.001), suggestive of an elastic phenomenon. A difference in recoil of the 3 main coronary branches was observed: left anterior descending artery 2.7 ± 1.3 mm2, circumflex artery 2.3 ± 1.2 mm2 and right coronary artery 1.9 ± 1.5 mm2 (p < 0.025). The difference was still statistically significant if adjusted for reference area. Thus, nearly 50% of the theoretically achievable cross-sectional area (i.e., balloon cross-sectional area) is lost shortly after balloon deflation.

No abstract is provided for this article.

Among patients who had undergone successful PCI for acute coronary syndromes, potent P2Y12 inhibitor monotherapy was not found to be noninferior to dual antiplatelet therapy with respect to a composite of death or ischemic events at 12 months. (Funded by the Brazilian Ministry of Health; NEO-MINDSET ClinicalTrials.gov number, NCT04360720.).

Background ST-elevation myocardial infarctions (STEMI) caused by proximal left-anterior descending (LAD) lesions have more myocardium at risk and worse outcomes than those located in other segments. The aim is to compare outcomes of patients with STEMI and proximal-LAD lesions treated with bare-metal stents (BMS) versus everolimus-eluting stents (EES). Methods The EXAMINATION trial randomized 1498 STEMI patients to BMS versus EES. The primary end point was the patient-oriented combined of all-cause death, any-recurrent myocardial infarction (MI) and any-revascularization. The secondary end point included the device-oriented combined of cardiac death, target-vessel MI and target-lesion revascularization (TLR). Results STEMI with a proximal-LAD occlusion was observed in 290 patients (BMS = 132 and EES = 158). Both groups were similar except for diabetes (12.9% vs 24.1%; P = .016). At 1 year, the primary end point was observed in 18.9% and 9.5% of patients treated with BMS and EES, respectively (P = .023). The secondary end point was observed in 11.4% and 5.1%, respectively (P = .053). There were no differences in cardiac death (4.5% vs 3.8%; P = .750) and MI (1.5% vs 0%; P = .121). BMS had higher rate of TLR compared to EES (6.8% vs 1.3%; P = .014). Patients with proximal-LAD STEMI had higher mortality than patients with non proximal-LAD STEMI (5.5% vs 2.9%; P = .027). Proximal-LAD lesions treated with BMS tended to increase the risk of the primary end point compared with other segments (18.9% vs 13.0%; P = .079). However, EES implanted in proximal-LAD had similar outcomes compared with other locations (9.5% vs 12.0%; P = .430). Adjusting for confounders, the interaction between BMS and proximal-LAD location was associated with the primary end point. Conclusion Patients with STEMI and proximal-LAD lesions treated with EES have better outcomes compared with BMS at 1 year. Although further investigations are required, it seems reasonable to consider EES for proximal-LAD STEMI-lesions.

Abstract Culture filtrate protein 10 kD (CFP10) and early secreted antigenic target of 6 kD (ESAT-6), are required in pathogenesis of tuberculosis in part by manipulation of host immunity. We reported the immune modulatory effects of ESAT-6, and the effect of CFP10 in this regard remains unexplored. We now demonstrate that recombinant CFP10 binds to peripheral blood B cells and monocytes, but not to T-cells. Stimulation of B cells through the B cell receptor BCR plus TLR9 induced IL-6, IL-8 and IL-10 production, and CFP10 but not rAg85 markedly reduced IL-10 secretion and mRNA expression, without affecting IL-6 and IL-8. CFP10 did not affect LPS-stimulated cytokine production by monocytes. CFP10 reduced BCR plusTLR9 stimulated B cell proliferation and IgG secretion. Using B cells as antigen-presenting cells, we found that CFP10 inhibited expression of CD80 and CD86, but not that of CD69 and MHC-II expression, resulting in reduced M. tuberculosis-specific T cell IFN-γ production. The effects of CFP10 on B cells were not due to changes in B-cell TLR9 expression, viability or apoptosis. However, CFP10 inhibited BCR plus TLR9 stimulated nuclear translocation of NF-κB, activation of AP-1 transcription factors and expression of BLIMP1, the master regulator of B cell maturation and activation. We conclude that CFP10 inhibits B functions by blocking TLR9 and BCR signaling, suggesting potential cell specific immune regulatory functions for CFP10 during tuberculosis infection.

Background Demonstration and quantification of site-specific intracoronary administration of compounds has been confined thus far to the experimental animal laboratory. The aim of this study was to describe a scintigraphic method to demonstrate site-specific intracoronary drug delivery in humans. The methods allow on-line visualization and off-line quantification of site-specifically infused γ-emitting compounds. Methods and Results In 12 patients after balloon angioplasty, 99m Tc-labeled heparin was administered at the site of dilatation by use of a coil balloon. Both the infusion period and the washout period after the end of infusion were monitored with a γ-camera. A curve of counts per pixel as a function of time was derived that showed an accumulation phase during infusion followed by a washout phase after the end of infusion. Both phases were fitted by regression analysis and showed a linear accumulation pattern and a biexponential washout pattern. After correction for background counts, 99m Tc decay, and body attenuation, peak heparin amount and regional bioavailability were calculated. Peak amount was defined as the initial point of the slow washout component of the biexponential curve (elimination component), and regional bioavailability was defined as the area under the curve of accumulation and washout phase. Half-life and retention time, defined as seven half-lives, were obtained by use of the elimination component after correction for 99m Tc decay. Mean peak delivered amount was 45±44 IU (236±228 μg), corresponding to an efficiency of delivery ranging from 1% to 8% of the totally infused dose. Total regionally bioavailable heparin reached 244±194 IU·h (1.28±1.01 mg·h). Retention time varied from 12 to 90 hours (mean, 50:33±22:50 hours:minutes). Conclusions Site-specific intracoronary heparin delivery after angioplasty by means of the coil balloon was demonstrated in humans, and regional pharmacokinetics was quantified by use of a radioisotopic technique.

COPD is associated with increased numbers of highly-activated lung macrophages (mφ) with reduced phagocytic ability. Mφ may exist as M1-like (classically-activated) or M2-like (alternatively-activated) states. In COPD, M1-like mφ may persist, and not respond to the environment. To test this, monocyte-derived mφ from non-smokers (NS), smokers (S) and COPD patients were cultured in GM-CSF (G-mφ, M1-like) or M-CSF (M-mφ, M2-like) for 12d (n=6-12). Media was switched for 6d and mφ stimulated with LPS. TNFα and IL-10 were measured by ELISA (n=2-3). Beads, H.influenzae (HI) or S.pneumoniae (SP) phagocytosis was measured fluorimetrically (n=10), CD163 and CD16 by FACS (n=3). All G-mφ released similar levels of TNFα and IL-10. Switching to M-CSF, TNFα release decreased in NS and S, but not COPD whereas IL-10 increased in NS but not S and COPD (Table 1). M-mφ from NS and S released less TNFα vs COPD but more IL-10. Switching to GM-CSF, IL-10 decreased in all mφ (Table 1). View this table: Table 1 Bead phagocytosis was similar by all mφ. G-mφ phagocytosed less HI and SP vs M-mφ in all groups (50%, p<0.05). All COPD mφ phagocytosed ∼45% less HI and SP vs NS, and expressed less CD163 and CD16. Culturing G-mφ in M-CSF, increased phagocytosis of HI (400%) and SP (200%) in NS vs S and COPD. Culturing M-mφ in GM-CSF, HI and SP phagocytosis was less in all mφ. COPD mφ appear “hyper-inflammatory” regardless of environment suggesting lack of plasticity. Altering COPD mφ plasticity may be a therapeutic target.

Wire arc additive manufacturing (WAAM) is a metal three-dimensional (3D) printing method that enables large-scale structural elements with complex geometry to be built in a relatively efficient and cost-effective manner, offering revolutionary potential to the construction industry. However, fundamental experimental data on the structural performance of WAAM elements, especially at the member level, are lacking. Hence, an experimental study into the flexural buckling response of WAAM tubular columns has been conducted and is presented in this paper. A total of 18 stainless steel square and circular hollow section (SHS and CHS) columns were tested under axial compression with pin-ended boundary conditions. Regular SHS and CHS profiles were chosen to enable direct comparisons against equivalent, conventionally manufactured sections and, hence, to isolate the influence of the additive manufacturing process, whereas the cross-section sizes and column lengths were varied to achieve a broad spectrum of member slendernesses. Given the geometric undulations inherent to the WAAM process, 3D laser scanning was used to determine the as-built geometry and global geometric imperfections of the specimens; digital image correlation (DIC) was employed to monitor the surface deformations of the specimens during testing. Full details of the column testing program, together with a detailed discussion of the experimental results, are presented. The applicability of the current column design provisions in EN 1993-1-4 and AISC 370 to WAAM stainless steel members was assessed by comparing the test results with the codified strength predictions. The comparisons emphasized the need to allow for the weakening effect of the inherent geometric variability of WAAM elements to achieve safe-sided strength predictions.

AIMS: Recent trials in humans have given us insight into some of the consequences of intracoronary radiation. The authors describe a new observation noted on intravascular ultrasound: that of intraluminal echolucent tissue, dubbed the 'black hole', noted at six-month follow-up. METHODS AND RESULTS: One hundred and twenty-eight consecutive patients enrolled in brachytherapy protocols were analyzed. The control group (C) consisted of individuals who underwent percutaneous transluminal coronary angioplasty with (n = 48) and without (n = 22) stent implantation. Radiation groups included those who underwent low activity (LA) (n = 18), high activity (HA) (n = 26) and cold-end (CE) (n = 18) radioactive stenting. The Novoste Betacath (n = 39) and Guidant (n = 27) catheter-based radiation systems were also employed. At six-month follow-up echolucent tissue was identified in a total of 28 cases (22%). Angiographic restenosis occurred in 17 cases (61%). No echolucent tissue was seen in the control group or in the LA group. HA and CE radioactive stents were most commonly associated with echolucent tissue. Echolucent tissue was seen in all groups treated with catheter-based radiation with and without stenting. Pathology after atherectomy demonstrated smooth muscle cells scattered in extracellular matrix containing abundant proteoglycans and an absence of elastin and mature collagen. CONCLUSIONS: Echolucent tissue is common after radioactive stenting. It is composed of tissue rich in proteoglycans while poor in mature collagen and elastin. (Int J Cardiovasc Intervent 2003; 5: 137-142)

No abstract is provided for this article.