Evaluation of Clinical and Genetic Determinants of Treatment OutCome In EGFR Mutation Positive Advanced Lung Adenocarcinoma.

Background: The aim of this research was to evaluate clinical and low-cost genetic determinants of treatment outcome in EGFR mutation positive advanced lung adenocarcinoma patients. Material and Methods: EGFR mutation testing and EGFR 181946C>T genotyping were performed in 101 advanced lung adenocarcinoma patients using qRT-PCR and PCR-RFLP, respectively. Progression-free survival was defined as the time from the start of TKI therapy to date of progression, and overall survival as the time from diagnosis to death from any cause. Pain level was evaluated using a Numerical Rating Scale and the Verbal Descriptor Scale. Statistical significance was considered for P < .05. Results: Patients were treated with EGFR-TKIs for a period of 1-39months (median 9), with a median PFS of 12.0 months (10.4-13.6, CI 95%), and a median OS of 19.0 months (15.1-22.7, CI 95%). The presence of pain was significantly correlated with the existence of bone (P < .001) and adrenal glands metastases (P = .029). Genetic factors did not have a direct impact on pain management but had a significant effect on the response to TKIs leading to pain alleviation. Conclusions: EGFR mutation subtype and the EGFR 181946 C>T SNP had a significant effect on the response to TKI inducing an indirect anti-dolorous effect.

Hematological parameters in EGFR-mutated advanced NSCLC patients treated with TKIs: predicting survival and toxicity.

Background: The aim of this study was to analyze the prognostic value of pre-treatment hematological parameters in EGFR-mutated non-small cell lung cancer patients treated with tyrosine-kinase inhibitors (TKIs).Patients and methods: Patients with EGFR mutations were treated with EGFR-TKIs in the first line until progression/unacceptable toxicity. Hematological parameters were derived from the absolute baseline differential counts of a complete blood count. The associations between the patients' and tumor characteristics were analyzed using Pearson Chi-Square, Fisher's exact, t-test, and Mann-Whitney tests. Cutoff values were determined using ROC curves, and correlation with survival was examined by Kaplan-Meier method and Cox regression.Results: Patients with NMR<12.62 had a longer PFS compared to patients with higher NMR values (12.0 vs. 10.0 months, p = 0.054) and a significantly longer OS (20.0 vs. 11.0 months, p = 0.010). The same parameter was confirmed as a predictors of favorable response in the patient subgroup with activating EGFR mutations. Patients with NLR>2.9 and LMR<2.5 more often presented with paronichia and diarrhea, and patients with PLR>190 more often had paronichia, diarrhea and hyperbilirubinemia.Conclusion: Low baseline value of the hematological parameter NMR has shown potential as a routine, low-cost, and minimally invasive predictor of survival in EGFR-TKI-treated NSCLC patients.

Cardiac Arrhythmias in Patients with Chronic Kidney Disease: Implications of Renal Failure for Antiarrhythmic Drug Therapy.

The kidney has numerous complex interactions with the heart, including shared risk factors (e.g., hypertension, dyslipidemia, etc.) and mutual amplification of morbidity and mortality. Both cardiovascular diseases and chronic kidney disease (CKD) may cause various alterations in cardiovascular system, metabolic homeostasis and autonomic nervous system that may facilitate the occurrence of cardiac arrhythmias. Also, pre-existent or incident cardiac arrhythmias such as atrial fibrillation (AF) may accelerate the progression of CKD. Patients with CKD may experience various cardiac rhythm disturbances including sudden cardiac death. Contemporary management of cardiac arrhythmias includes the use of antiarrhythmic drugs (AADs), catheter ablation and cardiac implantable electronic devices (CIEDs). Importantly, AADs are not used only as the principal treatment strategy, but also as an adjunct therapy in combination with CIEDs, to facilitate their effects or to minimize inappropriate device activation in selected patients. Along with their principal antiarrhythmic effect, AADs may also induce cardiac arrhythmias and the risk for such proarrhythmic effect(s) is particularly increased in patients with reduced left ventricular systolic function or in the setting of electrolyte imbalance. Moreover, CKD itself can induce profound alterations in the pharmacokinetics and pharmacodynamics of many drugs including AADs, thus facilitating the drug accumulation and increased exposure. Hence, the use of AADs in patients with CKD may be challenging. In this review article, we provide an overview of the characteristics of arrhythmogenesis in patients with CKD with special emphasis on the complexity of pharmacokinetics and risk for proarrhythmias when using AADs in patients with cardiac arrhythmias and CKD.

Non-Vitamin K Oral Anticoagulant Drugs for Stroke Prevention in Patients with Atrial Fibrillation and Chronic Kidney Disease.

Atrial fibrillation (AF) and chronic kidney disease (CKD) are disorders with increasing prevalence. The presence of CKD increases the risk of incident AF and vice versa, and the presence of AF may accelerate CKD progression. Nearly a third of patients with established CKD also have AF, whilst half of AF patients may have some degree of renal dysfunction. Both AF and CKD are associated with increased cardiovascular morbidity and mortality, including significantly increased risk of stroke or systemic embolism. Oral anticoagulant therapy (OAC), either with vitamin K antagonists or with non-vitamin K oral anticoagulants (NOACs) is essential to optimise prevention of stroke and systemic embolism in AF patients with one or more stroke risk factors, and NOACs are more convenient and generally safer than vitamin K antagonists mostly due to consistently reduced risk of intracranial bleeding. The use of OAC must be balanced against the risk of OAC-related bleeding, which depends on the presence of bleeding risk factors. Renal failure is a well-established bleeding risk factor and renal function should be routinely assessed in all patients presenting with AF. Since the risk of bleeding increases in parallel with CKD severity, the clinical decision to use OAC in AF patients with severe CKD may be challenging. In this review article we summarize the OAC agents currently used in clinical practice and discuss the role of NOACs for stroke prevention in patients with AF and CKD.