Long-term evaluation of home-based pulmonary rehabilitation in patients with COPD.

INTRODUCTION: Personalized, global pulmonary rehabilitation (PR) management of patients with COPD is effective, regardless of the place in which this rehabilitation is provided. The objective of this retrospective observational study was to study the long-term outcome of exercise capacity and quality of life during management of patients with COPD treated by home-based PR. METHODS: Home-based PR was administered to 211 patients with COPD (mean age, 62.3±11.1 years; mean forced expiratory volume in 1 second, 41.5%±17.7%). Home-based PR was chosen because of the distance of the patient's home from the PR center and the patient's preference. Each patient was individually managed by a team member once a week for 8 weeks with unsupervised continuation of physical exercises on the other days of the week according to an individual action plan. Exercise conditioning, therapeutic patient education, and self-management were included in the PR program. The home assessment comprised evaluation of the patient's exercise capacity by a 6-minute stepper test, Timed Up and Go test, ten times sit-to-stand test, Hospital Anxiety and Depression score, and quality of life (Visual Simplified Respiratory Questionnaire, VQ11, Maugeri Respiratory Failure 28). RESULTS: No incidents or accidents were observed during the course of home-based PR. The 6-minute stepper test was significantly improved after completion of the program, at 6 months and 12 months, whereas the Timed Up and Go and ten times sit-to-stand test were improved after PR and at 6 months but not at 12 months. Hospital Anxiety and Depression and quality of life scores improved after PR, and this improvement persisted at 6 months and 12 months. CONCLUSION: Home-based PR for unselected patients with COPD is effective in the short term, and this effectiveness is maintained in the medium term (6 months) and long term (12 months). Home-based PR is an alternative to outpatient management provided all activities, such as exercise conditioning, therapeutic education, and self-management are performed.

Predictors of advanced His-Purkinje conduction disturbances in patients with unexplained syncope and bundle branch block.

BACKGROUND: For patients presenting with syncope and bundle branch block (BBB), results during electrophysiological studies (EPS) might depend on the electrocardiographic pattern of conduction disturbances. We sought to identify predictors of advanced His-Purkinje conduction disturbances (HPCDs) in these patients. METHODS: In this retrospective multicentre study, patients were included who: (1) presented with unexplained syncope; (2) had BBB (QRS duration ≥ 120 ms); and (3) were investigated with EPS. HPCD was diagnosed if the baseline His-ventricular interval was ≥ 70 ms or if second- or third-degree His-Purkinje block was observed during atrial pacing or pharmacological challenge. RESULTS: Of the 171 patients studied (72 ± 13 years, 64% male sex, mean left ventricular ejection fraction 57 ± 9%), advanced HPCD was found in 73 patients (43%). The following electrocardiographic features were associated with HPCD (P = 0.01): isolated right BBB (34.4%), right BBB with left anterior fascicular block (36.4%), left BBB (46.2%), and right BBB with left posterior fascicular block (LPFB, 78.6%). Multivariate analysis identified first-degree atrioventricular block (odds ratio, 2.4; 95% confidence interval, 1.2-4.7; P = 0.01) and LPFB (odds ratio, 4.8; 95% confidence interval, 1.3-18.5; P = 0.02) as the only 2 independent predictors of advanced HPCD. CONCLUSIONS: For patients presenting with syncope and BBB, first-degree atrioventricular block and LPFB increased the likelihood of finding HPCDs during EPS. However, no single electrocardiographic feature could consistently predict the outcome of EPS, so this investigation is still necessary in assessing the need for pacemaker implantation, irrespective of the precise appearance of abnormalities on ECG.

Colon cancer cells escape 5FU chemotherapy-induced cell death by entering stemness and quiescence associated with the c-Yes/YAP axis.

PURPOSE: Metastasis and drug resistance are the major limitations in the survival and management of patients with cancer. This study aimed to identify the mechanisms underlying HT29 colon cancer cell chemoresistance acquired after sequential exposure to 5-fluorouracil (5FU), a classical anticancer drug for treatment of epithelial solid tumors. We examined its clinical relevance in a cohort of patients with colon cancer with liver metastases after 5FU-based neoadjuvant chemotherapy and surgery. RESULTS: We show that a clonal 5F31 cell population, resistant to 1 µmol/L 5FU, express a typical cancer stem cell-like phenotype and enter into a reversible quiescent G0 state upon reexposure to higher 5FU concentrations. These quiescent cells overexpressed the tyrosine kinase c-Yes that became activated and membrane-associated upon 5FU exposure. This enhanced signaling pathway induced the dissociation of the Yes/YAP (Yes-associated protein) molecular complex and depleted nuclear YAP levels. Consistently, YES1 silencing decreased nuclear YAP accumulation and induced cellular quiescence in 5F31 cells cultured in 5FU-free medium. Importantly, YES1 and YAP transcript levels were higher in liver metastases of patients with colon cancer after 5FU-based neoadjuvant chemotherapy. Moreover, the YES1 and YAP transcript levels positively correlated with colon cancer relapse and shorter patient survival (P < 0.05 and P < 0.025, respectively). CONCLUSIONS: We identified c-Yes and YAP as potential molecular targets to eradicate quiescent cancer cells and dormant micrometastases during 5FU chemotherapy and resistance and as predictive survival markers for colon cancer.