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Iglesias P.,Hospital Ramon y Cajal | Pedro-Botet J.,Hospital Del Mar | Arrieta F.,Hospital Ramon y Cajal | Aguilar M.,Hospital Puerta Del Mar | Escobar F.,Hospital Clinico
Current Diabetes Reviews | Year: 2015

The prevalence of type 2 diabetes mellitus (T2DM) has risen in recent decades, and cardiovascular disease (CVD) remains the leading cause of death in this population. Several studies have shown that, in clinical practice, identifying diabetic patients at high risk for CVD is essential, since these patients benefit from aggressive strategies to achieve a greater risk reduction. In recent years, new markers of CV risk have been added to the list of those already known. These new emerging markers, such as inflammatory, bone and hormonal markers, act as new indicators of subclinical atherosclerosis and CV mortality. Therefore, we reviewed the ongoing scientific research on these new biomarkers and discuss their clinical impact on the identification of T2DM patients at high CV risk. © 2015 Bentham Science Publishers.

Alvarez-Garcia J.,Autonomous University of Barcelona | Ferrero-Gregori A.,Autonomous University of Barcelona | Puig T.,Autonomous University of Barcelona | Vazquez R.,Hospital Puerta Del Mar | And 8 more authors.
European Journal of Heart Failure | Year: 2015

Aims Prevention of hospital readmissions is one of the main objectives in the management of patients with heart failure (HF). Most of the models predicting readmissions are based on data extracted from hospitalized patients rather than from outpatients. Our objective was to develop a validated score predicting 1-month and 1-year risk of readmission for worsening of HF in ambulatory patients. Methods and results A cohort of 2507 ambulatory patients with chronic HF was prospectively followed for a median of 3.3 years. Clinical, echocardiographic, ECG, and biochemical variables were used in a competing risk regression analysis to construct a risk score for readmissions due to worsening of HF. Thereafter, the score was externally validated using a different cohort of 992 patients with chronic HF (MUSIC registry). Predictors of 1-month readmission were the presence of elevated natriuretic peptides, left ventricular (LV) HF signs, and estimated glomerular filtration rate (eGFR) <60 mL/min/m2. Predictors of 1-year readmission were elevated natriuretic peptides, anaemia, left atrial size >26 mm/m2, heart rate >70 b.p.m., LV HF signs, and eGFR <60 mL/min/m2. The C-statistics for the models were 0.72 and 0.66, respectively. The cumulative incidence function distinguished low-risk (<1% event rate) and high-risk groups (>5% event rate) for 1-month HF readmission. Likewise, low-risk (7.8%), intermediate-risk (15.6%) and high-risk groups (26.1%) were identified for 1-year HF readmission risk. The C-statistics remained consistent after the external validation (<5% loss of discrimination). Conclusion The Redin-SCORE predicts early and late readmission for worsening of HF using proven prognostic variables that are routinely collected in outpatient management of chronic HF. © 2015 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Garcia-Baquero R.,Tumor Markers Group | Puerta P.,Tumor Markers Group | Beltran M.,Hospital Puerta Del Mar | Alvarez M.,Hospital Central de Asturias | And 3 more authors.
Journal of Urology | Year: 2013

Purpose: Changes in DNA methylation of tumor suppressor genes early in carcinogenesis represent potential indicators of cancer detection and disease evolution. We examined the diagnostic, stratification and prognostic biomarker roles in urine of the methylation of a novel panel of tumor suppressor genes in bladder cancer. Material and Methods: We evaluated the methylation of 18 tumor suppressor genes in 2 prospective, independent sets of urine samples (training set of 120 preparations and validation set of 128) from patients with bladder cancer (170) and controls (78) using methylation specific multiplex ligation-dependent probe amplification. Diagnostic performance was evaluated with ROC curves. Recurrence, progression and disease specific survival were analyzed using univariate and multivariate Cox models. Results: PRDM2, HLTF, ID4, DLC1, BNIP3, H2AFX, CACNA1G, TGIF and CACNA1A were methylated in bladder cancer. CCND2, SCGB3A1, BNIP3, ID4 and RUNX3 were the most frequently methylated tumor suppressor genes in each urine set. Methylation of several tumor suppressor genes correlated with clinicopathological variables, such as stage, tumor grade, focality or age. ROC analysis revealed significant diagnostic accuracy for RUNX3 and CACNA1A in the training set, and for RUNX3 and ID4 in the validation set. On univariate and multivariate analysis CACNA1A methylation correlated with recurrence in the training set, while in the validation set PRDM2 and BNIP3 were significantly associated with recurrence and disease specific survival, respectively. Conclusions: Tumor suppressor gene methylation allowed for histopathological and clinical stratification. Urine methylation has noninvasive usefulness not only for diagnostic assessment but also as independent bladder cancer prognosticators. © 2013 American Urological Association Education and Research, Inc.

Radbruch L.,Universitatsklinikum Bonn | Torres L.M.,Hospital Puerta Del Mar | Ellershaw J.E.,Marie Curie Palliative Care Institute | Gatti A.,University of Rome Tor Vergata | And 2 more authors.
Supportive Care in Cancer | Year: 2012

Purpose: Previous studies show that fentanyl pectin nasal spray (FPNS) rapidly provides clinically meaningful pain relief in the treatment of breakthrough cancer pain (BTCP). This study assessed the long-term tolerability, acceptability and consistency of effect of FPNS in patients with BTCP. Methods: Patients (new and rolled over from earlier controlled studies) with cancer experiencing one to four episodes per day of BTCP whilst taking ≥60 mg/day of morphine (or equivalent) given orally for cancer pain entered an open-label 16-week safety study. Safety and tolerability were assessed by adverse events (AEs), adverse drug reactions (ADRs), withdrawal due to AEs and by nasal assessments. Acceptability assessments included ratings of overall satisfaction with each treated episode and ease of use and convenience of FPNS. Additional rescue medication and dose stability were used to evaluate the consistency of effect. Results: Four hundred three patients were included in the safety and intent-to-treat analysis (42,227 episodes), 356 entered the treatment phase and 110 completed 16 weeks. Overall, 24.6% of 403 patients reported treatment-related treatment-emergent AEs that were generally mild/moderate and typical of opioids; 20 patients discontinued treatment due to an AE (9 were ADRs). Nasal assessments revealed no clinically significant effects; 94% of FPNS-treated episodes required no additional rescue medication. More than 90% of patients did not have to increase their dose during the study. Patients reported overall satisfaction with FPNS for 90.1% of episodes. At week 12, 96.9% of patients were satisfied with the ease of use and 97.9% with the convenience of FPNS. Conclusions: FPNS was generally well tolerated and well accepted for the treatment of BTCP, and doses remained stable over the 4-month study period. © 2011 Springer-Verlag.

Puerta-Gil P.,Tumor Markers Group | Garca-Baquero R.,Hospital Puerta Del Mar | Jia A.Y.,Columbia University | Ocaa S.,Hospital Fundacion de Alcorcon | And 5 more authors.
American Journal of Pathology | Year: 2012

Altered microRNA (miRNA) expression may occur early in bladder cancer and may play a role in carcinogenesis and tumor behavior. We evaluated whether alterations in miRNA expression could improve disease stratification and outcome prognosis in bladder tumors and noninvasive diagnosis in urinary samples. miR-143, miR-222, and miR-452 expression levels were analyzed by quantitative RT-PCR (RT-qPCR) in paired urinary and matching tumors and in two independent prospective series of tumors and urinary specimens. Differential expression of miR-143, miR-222, and miR-452 in urine were verified by in situ hybridization in matching tumors. Tumor miRNA expression by RT-qPCR correlated with tumor grade, size, and presence of carcinoma in situ for miR-222, recurrence (miR-222 and miR-143), progression (miR-222 and miR-143), disease-specific survival (miR-222), and overall survival (miR-222). Protein expression patterns of potential miRNA targets, including vascular endothelial growth factor, BCL2, v-erb-b2 erythroblastic leukemia viral oncogene (ERBB) homolog 3, and ERBB4, were evaluated by IHC in tissue arrays containing tumors for which miRNAs were assessed by RT-qPCR. Target expression correlated with expression of their predicted regulatory miRNAs, recurrence (ERBB3), progression (ERBB4), disease-specific survival (ERBB3 and ERBB4), and overall survival (ERBB3 and ERBB4). Furthermore, RT-qPCR of miR-452 (area under the curve, 0.848) and miR-222 (area under the curve, 0.718) in urine provided high accuracies for bladder cancer diagnosis. Thus, bladder tumors were characterized by changes in miRNA expression that could aid in tumor stratification and clinical outcome prognosis, and miRNAs were detected in urinary specimens for noninvasive diagnosis. © 2012 American Society for Investigative Pathology.

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