AimsTo address the incremental usefulness of biomarkers from different disease pathways for predicting risk of death in heart failure (HF). Methods and resultsWe used data from consecutive patients treated at a structured multidisciplinary HF unit to investigate whether a combination of biomarkers reflecting ventricular fibrosis, remodelling, and stretch [ST2 and N-terminal pro brain natriuretic peptide (NTproBNP)] improved the risk stratification of a HF patient beyond an assessment based on established mortality risk factors (age, sex, ischaemic aetiology, left ventricular ejection fraction, New York Heart Association functional class, diabetes, glomerular filtration rate, sodium, haemoglobin, and beta-blocker and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker treatments). ST2 was measured with a novel highsensitivity immunoassay. During a median follow-up time of 33.4 months, 244 of the 891 participants in the study (mean age 70.2 years at baseline) died. In the multivariable Cox proportional hazards model, both ST2 and NTproBNP significantly predicted the risk of death. The individual inclusion of ST2 and NTproBNP in the model with established mortality risk factors significantly improved the C statistic for predicting death [0.79 (0.76-0.81); P , 0.001]. The net improvement in reclassification after the separate addition of ST2 to the model with established risk factors and NTproBNP was estimated at 9.90% [95% confidence interval (CI) 4.34-15.46; P , 0.001] and the integrated discrimination improvement at 1.54 (95% CI 0.29 -2.78); P ¼ 0.015). ConclusionsOur data suggest that in a real-life cohort of HF patients, the addition of ST2 and NTproBNP substantially improves the risk stratification for death beyond that of a model that is based only on established mortality risk factors.--

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BackgroundMatrix metalloproteases (MMPs) are proteolytic enzymes that contribute to all stages of tumour progression, including the later stages of invasion and metastasis. Genetic variants in the MMP genes may influence the biological function of these enzymes and change their role in carcinogenesis and progression. We have investigated the association between the -735 C/T, the -1171 5A/6A, and the -1562 C/T polymorphisms in the MMP2, MMP3 and MMP9 genes, respectively, and the risk and survival of lung cancer.MethodsThe case-control study includes 879 lung cancer patients and 803 controls from a Caucasian population in Spain (CAPUA study). Genotypes were determined by PCR-RFLP. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression. The Kaplan-Meier method, long-rank test and Cox's were used for the survival analysis.ResultsThe MMP9 -1562 T/T genotype was associated with a statistically significant decreased risk of developing lung cancer (OR = 0.23; 95% CI: 0.06-0.85), whereas no association was found for the MMP2 -735 C/T and MMP3 -1171 5A/6A polymorphisms. The MMP2 -735 T/T genotype was statistically significantly associated with a decreased survival in non-small cell lung cancer (NSCLC) patients, identified as an independent prognosis factor of survival (hazard ratio (HR) = 1.79; 95% CI: 1.00-3.20). In contrast, no association was found between the MMP3 -1171 5A/6A and the MMP9 -1562 C/T polymorphisms and survival.ConclusionsThese findings support the hypothesis that the MMP9 -1562 C/T polymorphism is associated with a protective effect against the development of lung cancer and suggest that the MMP2 -735 C/T polymorphism modify the length of survival in NSCLC patients.

Summary This study was designed to assess the efficacy and safety of an infusional DA‐EPOCH (dose‐adjusted etoposide/vincristine/doxorubicin/bolus cyclophosphamide/prednisone) and rituximab (DA‐EPOCH‐R) regimen for patients with poor prognosis diffuse large B‐cell lymphoma (DLBCL). Thirty‐three patients, aged 21–76 years, with an age‐adjusted International Prognostic Index (IPI) of 2 or 3, were enrolled, and 31/33 patients were evaluable for response. Consolidative radiation therapy was given to eight patients with bulky (≥10 cm) disease at presentation. Overall, 26 patients (83·8%) achieved a complete remission (CR), four patients (12·9%) achieved a partial remission, and one patient (3·2%) died during induction. Two patients relapsed (7·6%) within 15 months. Grade 3–4 neutropenia developed in 52% of cycles and neutropenic fever in 14% of cycles (51% of patients). The estimates for event‐free survival (EFS) and overall survival at 2 years were 68% and 75% respectively. The only factor related to poor EFS was the presence of three age‐adjusted IPI‐risk factors. We conclude that DA‐EPOCH‐R has clinically significant activity with a favourable toxicity profile for poor‐prognostic DLBCL patients. The administration of DA‐EPOCH‐R as an outpatient regimen by using a single portable infusion pump may be a feasible alternative to improve the compliance and to reduce the total cost of this very effective regimen.