Chronic Obstructive Pulmonary Disease and Lung Cancer: Underlying Pathophysiology and New Therapeutic Modalities

Chronic obstructive pulmonary disease (COPD) and lung cancer are major lung diseases affecting millions worldwide. Both diseases have links to cigarette smoking and exert a considerable societal burden. People suffering from COPD are at higher risk of developing lung cancer than those without, and are more susceptible to poor outcomes after diagnosis and treatment. Lung cancer and COPD are closely associated, possibly sharing common traits such as an underlying genetic predisposition, epithelial and endothelial cell plasticity, dysfunctional inflammatory mechanisms including the deposition of excessive extracellular matrix, angiogenesis, susceptibility to DNA damage and cellular mutagenesis. In fact, COPD could be the driving factor for lung cancer, providing a conducive environment that propagates its evolution. In the early stages of smoking, body defences provide a combative immune/oxidative response and DNA repair mechanisms are likely to subdue these changes to a certain extent; however, in patients with COPD with lung cancer the consequences could be devastating, potentially contributing to slower postoperative recovery after lung resection and increased resistance to radiotherapy and chemotherapy. Vital to the development of new-targeted therapies is an in-depth understanding of various molecular mechanisms that are associated with both pathologies. In this comprehensive review, we provide a detailed overview of possible underlying factors that link COPD and lung cancer, and current therapeutic advances from both human and preclinical animal models that can effectively mitigate this unholy relationship

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Characteristics of Overvoltage Protection with Cascade Application of Surge Protective Devices in Low-Voltage AC Power Circuits

Surge Protective Devices (SPDs) are widely used for protection of the equipment in low-voltage AC power circuits against wide variety of surges. Cascade application of SPDs starting at the service entrance of a building and downstream toward near sensitive equipment is intended to ensure optimal energy distribution among installed SPDs, as well as proper equipment protection against surges. Characteristics of overvoltage protection with two-stage application of SPDs have been analyzed in the paper through performed measurements, followed by simulations and numerical modeling using the ATP/EMTP and MATLAB Simulink. Parametric analysis of the protection's characteristics in wide range of influencing factors has been performed in order to define a set of applicable solutions for proper selection and performance of SPDs

Least Squares Modeling of Voltage Harmonic Distortion Due to PC Cluster Operation

Regarding the possibility of harmonic generation, personal computers (PCs) are very significant within the category of non-linear low power loads. In modern distribution systems, the number of PCs simultaneously connected to distribution grid constantly increases. This PC clustering can negatively affect the quality of supply. The paper deals with mathematical modeling of the voltage total harmonic distortion (THDU) caused by operation of PC cluster. The proposed model is based on the power quality measurements carried out in a computer centre and computer simulations. It takes into account the THDU dependence on the PC cluster size and grid stiffness. Model parameters are derived in the least squares sense. The influences of cable cross-section and pre-existing THDU of the phase voltage are also discussed. The accuracy of the proposed model is confirmed by additional measurements performed in a commercial building

The Impact of the Load Side Parameters on PC Cluster's Harmonics Emission

Harmonics current emission from personal computers (PCs) is of special interest to power quality researchers, due to their wide spread application and the fact that they are usually concentrated in large groups (clusters). The input current total harmonic distortion (THDI) dependence on number of connected PCs in a cluster (NPC) is affected by network parameters and load side parameters of each cluster's PC simultaneously. As the impact of grid parameters on the THDI=f(NPC) dependence is analyzed in the author's previous papers, special emphasis is given on the impact of the DC side smoothing capacitor (C) in PCs power supply unit. For engineering application it is convenient to present the THDI=f(NPC) function with simple mathematical expressions which include these effects. In the paper authors are proposing an improved mathematical expression to presents impact of load side (DC capacitance) parameters. To achieve this goal, results of the measurements of harmonic emission from a large computer center with 167 clustered PCs and the computer simulation for even larger number of PCs are used

The role of amiodarone in contemporary management of complex cardiac arrhythmias

Amiodarone is an iodinated benzofuran derivative, a highly lipophilic drug with unpredictable pharmacokinetics. Although originally classified as a class III agent due to its ability to prolong refractoriness in cardiac regions and prevent/terminate re-entry, amiodarone shows antiarrhythmic properties of all four antiarrhythmic drug classes. Amiodarone is a potent coronary and peripheral vasodilator and can be safely used in patients with left ventricular dysfunction after myocardial infarction or those with congestive heart failure or hypertrophic cardiomyopathy. Its use is regularly accompanied with QT and QTc-interval prolongation but rarely with ventricular proarrhythmia. It is the most powerful pharmacological agent for long-term sinus rhythm maintenance in patients with atrial fibrillation. Amiodarone, particularly if co-administered with beta-blockers, reduces the rate of arrhythmic death due to ventricular tachyarrhythmias in patients with heart failure, but its benefit on cardiovascular and overall survival in these patients is uncertain. In addition, amiodarone is an important adjuvant drug for the reduction of shocks in patients with an implantable cardioverter-defibrillator. Over the past 40 years, amiodarone became the most prescribed antiarrhythmic. Nevertheless, the slow onset of its antiarrhythmic action requires a loading dose while the high risk of non-cardiac toxicity and common drug-drug interactions limit its long-term use. Furthermore patients treated with amiodarone require a close supervision by the treating physician. Therefore amiodarone is generally considered a secondary therapeutic option. Long-term treatment with amiodarone should be based on the use of minimal doses for satisfactory arrhythmia outcome and serial screening for thyroid, liver and pulmonary toxicity