Because it is inexpensive, theophylline remains one of the most widely prescribed drugs for the treatment of airway diseases world-wide. In many industrialized countries, however, theophylline has become a third-line treatment used only in poorly controlled patients. This has been reinforced by various guidelines to therapy. Some have even questioned whether theophylline is indicated in any patients with asthma [1], although others have emphasized the special beneficial effects of theophylline which still give it an important place in management of asthma and chronic obstructive pulmonary disease (COPD) [2•]. However, the frequency of side effects and the relative low efficacy of theophylline have led to reduced usage, because inhaled β2-agonists are far more effective as bronchodilators, and inhaled corticosteroids have a greater anti-inflammatory effect. Considerable uncertainty about the mode of action of theophylline in asthma and its logical place in therapy remain, despite its long-term use in asthma therapy. Because of problems with side effects, there have been attempts to improve on theophylline; recently, there has been increasing interest in selective phosphodiesterase (PDE) inhibitors. Selective PDE4 inhibitors, a cAMP-specific family that negatively regulates the function of almost all pro-inflammatory and immune cells and exerts widespread anti-inflammatory activity in animal models of asthma, have the possibility of improving the beneficial effects and reducing the adverse effects of theophylline, although existing inhibitors are limited by the same side effects as theophylline [3].
This study investigated the differences in clinical outcomes between patients with bifurcation lesions (BL) treated with a biolimus-eluting stent (BES) with a biodegradable polymer, and a sirolimus-eluting stent (SES) with a durable polymer.The clinical outcomes were assessed in the 497 patients (BES 258, SES 239) enrolled in the multicentre, randomised LEADERS trial who underwent treatment of ≥1 BL (total=534 BL). At 12-months follow-up there was no significant difference in the primary endpoint of MACE, a composite of cardiac death, myocardial infarction and clinically indicated target vessel revascularisation (BES 12.8% vs. SES 16.3%, p=0.31). Patients treated with BES had comparable rates of cardiac death (BES 2.7% vs. SES 2.9%, p=1.00), numerically higher rates of myocardial infarction (BES 8.9% vs. SES 5.4%, p=0.17), and significantly lower rates of clinically indicated target vessel revascularisation (4.3% vs. 11.3%, p=0.004) when compared to those treated with SES. The rate of stent thrombosis at 12-months was 4.3% and 3.8% for BES and SES, respectively (p=0.82).In the treatment of BL the use of BES lead to superior efficacy and comparable safety compared to SES.
The presence of thrombus is associated with adverse clinical outcomes. Our aim was to develop a classification of thrombus burden (TB) in patients with ST-segment elevation myocardial infarction (STEMI).We retrospectively analyzed 900 consecutive patients treated with percutaneous coronary intervention for STEMI. Drug-eluting stents were used in 90.1%. TB was graded (G) as G0 = no thrombus, G1 = possible thrombus, G2 = small [greatest dimension ≤ 1/2 vessel diameter (VD)], G3 = moderate (> 1/2 but < 2VD), G4 = large (≥ 2VD), G5 = unable to assess TB due to vessel occlusion. Patients with G5 were reclassified to a thrombus category after flow achievement either with a guidewire or a small (1.5 mm) balloon. The incidence of major adverse cardiac events (MACE) - defined as death, myocardial infarction and infarct-related artery revascularization - was computed using the Kaplan-Meier method.Median duration of follow-up was 18.5 months. G5 patients constituted 57.7% of all patients and reclassification was achieved in 97.9%. TB after reclassification was G0, 8.1%; G1, 19%; G2, 24.5%, G3,16.6%, G4, 30%, G5, 1.9%. The 2-year cumulative MACE-free survival was comparable in G1, G2, G3 (84.5%, 85.9% and 87% respectively, p = 0.83), while G0 (75.8%) and G4 (75%) did significantly worse (p = 0.001). After stratification in two groups of small (G0-3) and large (G4) TB, the latter was found to be an independent predictor for 2-year mortality (HR: 1.66, 95% CI: 1.04-2.68, p = 0.035) and MACE rate (HR: 2.04, 95% CI: 1.44-2.88, p < 0.001).In patients with STEMI, TB can be reliably estimated in occluded infarct-related arteries. Large thrombus (≥ 2 VD) is a significant independent predictor for mortality and MACE.
Advances in additive manufacturing are increasingly allowing bespoke, carefully designed, metamaterial lattice structures to be constructed for enhanced mechanical performance. For instance, in structural elements that are designed to absorb energy and shield a more valuable structure, the properties combining a high initial stiffness followed by a practically zero underlying stiffness, ensure that a desired energy quantity may be absorbed within a limited displacement and that any stress transfer to the valuable structure is minimized. Presently, a lattice structure is studied that is deliberately designed to switch locally under compression between conventional material behaviour to that exhibiting auxetic (negative Poisson's ratio) behaviour through a sequence of snap-through instabilities within layers of individual lattice cells. The sequence of buckling instabilities can potentially be controlled to maintain the loading level alongside the low structural stiffness while the required energy quantity is absorbed, without necessarily damaging the material in the process. This departs from the usual paradigm where such structures are presently designed to be sacrificial and opens up the intriguing possibility of introducing such structural elements that are repairable and therefore reusable.
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