A mRNA panel for differentiation between acute exacerbation or pneumonia in COPD patients.

Introduction: Patients suffering from chronic obstructive pulmonary disease (COPD) are prone to acute exacerbations (AECOPD) or community acquired pneumonia (CAP), both posing severe risk of morbidity and mortality. There is no available biomarker that correctly separates AECOPD from COPD. However, because CAP and AECOPD differ in aetiology, treatment and prognosis, their discrimination would be important. Methods: This study analysed the ability of selected candidate transcripts from peripheral blood mononuclear cells (PBMCs) to differentiate between patients with AECOPD, COPD & CAP, and CAP without pre-existing COPD. Results: In a previous study, we identified differentially regulated genes between CAP and AECOPD in PBMCs. In the present new cohort, we tested the potential of selected candidate PBMC transcripts to differentiate at early time points AECOPD, CAP+COPD, and CAP without pre-existing COPD. Expression of YWHAG, E2F1 and TDRD9 held predictive power: This gene set predicted diseases markedly better (model accuracy up to 100%) than classical clinical markers like CRP, lymphocyte count and neutrophil count (model accuracy up to 82%). Discussion: In summary, in our cohort expression levels of YWHAG, E2F1 and TDRD9 differentiated with high accuracy between COPD patients suffering from acute exacerbation or CAP.

Survival following Multimodality Treatment Including Surgery for Stage IA-IIIB Small-Cell Lung Cancer.

BACKGROUND: Prognosis in limited disease small-cell lung cancer (SCLC) after concurrent chemoradiotherapy is poor. While some studies show better survival after multimodality treatment including surgery, other trials failed to prove a surgery-related survival benefit. Therefore, this study investigated survival in stage IA-IIIB SCLC following surgery combined with chemotherapy and/or thoracic radiotherapy. METHODS: We retrospectively reviewed all stage IA-IIIB SCLC patients without supraclavicular lymph node involvement at a single institution between January 1999 and August 2016 after multimodality treatment with curative intent. This comprised surgery consisting of primary tumor resection and systematic lymph node dissection combined with chemotherapy, chemoradiotherapy, or thoracic radiotherapy. Survival was determined using the Kaplan-Meier method, and differences were compared using log-rank tests. The risk of locoregional relapse was calculated. RESULTS: A total of 47 patients (29 men, 18 women; mean age: 62 years) were included. Thirty-day mortality was 0%. Overall median survival was 56 months, and 2-, 3-, 5-, and 10-year survival rates were 69, 54, 46, and 30%, respectively. The only significant prognostic factor (p = 0.006) was R0 resection (n = 40) increasing median survival to 64 versus 17 months in case of technical inoperability (n = 5). The risk of locoregional relapse was 2.5% (n = 1) after R0 resection. CONCLUSIONS: Multimodality treatment including surgery was safe and led to considerable survival. R0 resection was the only factor extending survival. It could be achieved in most patients and was associated with a low risk of locoregional relapse. Prospective randomized controlled studies are needed to define best practice in stage IA-IIIB SCLC.

Increased myocardial oxygen consumption by TNF-alpha is mediated by a sphingosine signaling pathway.

The present study investigated the effect of tumor necrosis factor (TNF)-alpha on myocardial energy metabolism as estimated by myocardial oxygen consumption (MVo(2)). MVo(2) of electrically stimulated isolated trabeculae of right ventricular Wistar rat myocardium was analyzed using a Clark-type oxygen probe. After the initial data collection in the absence of TNF-alpha, measurements were repeated after TNF-alpha stimulation. In separate experiments, pretreatment with the nitric oxide (NO) synthase inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME) or the ceramidase inhibitor n-oleoylethanolamine (NOE) was done to investigate NO/sphingosine-related effects. TNF-alpha impaired myocardial economy at increasing stimulation frequencies without altering baseline MVo(2). Incubation with TNF-alpha in the presence of l-NAME further impaired myocardial economy. NOE preincubation abrogated the TNF-alpha effect on myocardial economy. Moreover, the negative inotropic effect of TNF-alpha was observed in NOE-pretreated but not l-NAME-pretreated muscle fibers. Exogenous sphingosine mimicked the TNF-alpha effect on mechanics and energetics. We conclude that TNF-alpha impairs the economy of chemomechanical energy transduction primarily through a sphingosine-mediated pathway.