Nuestros investigadores

Nerea Varo Cenarruzabeitia

Publicaciones científicas más recientes (desde 2010)

Autores: Macias, Monica; Alegre, Estíbaliz; Díaz-Lagares, A.; et al.
ISSN 0065-2423  Vol. 83  Nº 73  2018  págs. 73 - 119
Liquid biopsy refers to the molecular analysis in biological fluids of nucleic acids, subcellular structures, especially exosomes, and, in the context of cancer, circulating tumor cells. In the last 10 years, there has been an intensive research in liquid biopsy to achieve a less invasive and more precise personalized medicine. Molecular assessment of these circulating biomarkers can complement or even surrogate tissue biopsy. Because of this research, liquid biopsy has been introduced in clinical practice, especially in oncology, prenatal screening, and transplantation. Here we review the biology, methodological approaches, and clinical applications of the main biomarkers involved in liquid biopsy.
Autores: Pérez-Pevida, Belén; Idoate, Miguel Ángel; Fernández, Sara; et al.
ISSN 1046-3976  Vol. 27  Nº 1  2016  págs. 50-54
The most common cause of organic fasting hypoglycemia in adults is the presence of an insulin-producing pancreatic adenoma, but when high insulin levels are not found, the differential diagnosis is challenging. Misdiagnosis can lead to an unnecessary pancreatectomy. Insulin concentrations may be low in some cases despite a clinical history suggestive of insulinoma. In these cases, a proinsulinoma should be suspected, although the rarity of this condition requires an extensive workup before reaching a final diagnosis. We describe an unusual case of a 38-year-old man with a severe hypoglycemic syndrome due to a proinsulin-secreting pancreatic adenoma. Insulin was measured by the specific assay and suppressed under the lower detection limit during fasting hypoglycemia. Serum proinsulin and C-peptide levels were abnormally elevated, and further tests revealed an islet cell tumor. The tumor was surgically removed, relieving the fasting hypoglycemia. Histopathological study showed a conventional well-differentiated neuroendocrine tumor with high immunoreactivity against proinsulin and with lesser intensity against insulin. Interestingly, GS-9A8 antibody clone used for immunostaining proinsulin did not cross-react with human insulin or C-peptide, providing an unbiased picture of proinsulin secretion. The resolution of symptoms, the fall of proinsulin concentrations after tumor removal and the histopathology study confirmed the diagnosis of proinsulinoma
Autores: González, Jéssica; Restituto, Patricia; et al.
ISSN 1073-449X  Vol. 193  2016  págs. A3554
Autores: Lawrie, A.; Varo, N;
ISSN 1687-8337  Vol. 2015  2015  págs. 564934
Osteoprotegerin (OPG), a glycoprotein traditionally implicated in bone remodelling, has been recently related to cardiovascular disease (CVD). Human studies show a positive relationship between circulating OPG, vascular damage, and CVD, and as such OPG has emerged as a potential biomarker for CVD. This review focuses on the relationship between circulating OPG and different endocrine cardiometabolic alterations such as type 1 and 2 diabetes. The association of OPG with diabetic complications (neuropathy, nephropathy, or retinopathy) as well as with atherosclerosis, coronary artery calcification, morbidity, and mortality is pointed out. Moreover, OPG modulation by different treatments is also established. Besides, other associated diseases such as obesity, hypertension, and metabolic syndrome, which are known cardiovascular risk factors, are also considered.
Autores: Ravassa, S; Kuznetsova, T.; Varo, N; et al.
ISSN 0167-5273  Vol. 185  2015  págs. 177 - 185
BACKGROUND/OBJECTIVES: The validation of effective screening tools for the identification of patients with subclinical myocardial remodelling is a major clinical need. Thus, we explored the associations of circulating biomarkers of cardiomyocyte injury and stress with subclinical cardiac remodelling and dysfunction, and with biomarkers reflecting collagen turnover. METHODS: We randomly recruited 727 subjects from a general population (51.2% women; mean age 51.3 years). Measurements included echocardiographic left atrial (LA) and left ventricular (LV) structure and function, quantification of high sensitivity cardiac Troponin T (hs-cTnT), NT-proBNP, and biomarkers of collagen types I and III turnover. RESULTS: In unadjusted and adjusted analyses, the prevalence of LA enlargement (LAE), LV hypertrophy (LVH) and LV diastolic dysfunction (LVDD) increased with higher hs-cTnT (P ¿ 0.031). NT-proBNP was independently associated with LVDD (P=0.009). Both biomarkers combined yielded significant integrated discrimination and net reclassification improvements (P ¿ 0.014 and P ¿ 0.009, respectively) for LAE, LVH and LVDD, over the conventional risk factors, and were independently and positively associated with biomarkers of collagen type I turnover. In a sensitivity analysis, after excluding participants with previous cardiac diseases, our findings remained consistent. CONCLUSIONS: Our population-based study suggested that subclinical LV and LA remodelling were associated with hs-cTnT, and that, in combination with NT-proBNP, hs-cTnT showed incremental diagnostic utility over the conventional risk factors. Both biomarkers were associated with biomarkers of collagen type I turnover. Thus, biomarkers of cardiomyocyte microinjury and hemodynamic stress may stimulate fibrosis-related mechanisms and facilitate the diagnosis of subclinical LA and LV remodelling and dysfunction in the general population.
Autores: Martín, Paloma Leticia; Varo, N; Martín, Nerea; et al.
ISSN 1660-8151  Vol. 131  Nº 1  2015  págs. 51-58
We evaluated the effectiveness of oral sodium citrate versus intravenous (IV) sodium bicarbonate for CI-AKI prophylaxis as well as their influence on kidney injury biomarkers. Material and Methods: A randomized, controlled, single-center study including 130 hospitalized patients (62.3% men), who were randomized to receive sodium bicarbonate (1/6 men, 3 ml/kg/h for 1 h; n = 43), oral sodium citrate (75 ml/10 kg divided into 4 doses; n = 43) or nonspecific hydration (n = 44) before contrast administration, was conducted. Serum creatinine and kidney injury biomarkers (cystatin C, neutrophil gelatinase-associated lipocalin, interleukin-8, F2-isoprostanes and cardiotrophin-1 [CT-1]) were assessed. Results: Incidence of CI-AKI was 9.2% with no differences found between hydration groups: 7.0% in sodium bicarbonate group, 11.6% in oral sodium citrate group and 9.1% in the nonspecific hydration group. Urinary creatinine and urinary CT-1/creatinine ratio decreased 4 h after contrast infusion (p < 0.001), but none of the biomarkers assessed were affected by the treatments. Conclusions: There were no differences in hydration with oral sodium citrate and IV sodium bicarbonate for the prophylaxis of CI-AKI. Therefore, oral hydration represents a safe, inexpensive and practical method for preventing CI-AKI in low-risk patients. No effect on biomarkers for kidney injury could be demonstrated.
Autores: Iñarrairaegui, Mercedes; Páramo, José Antonio; et al.
ISSN 1478-3223  Vol. 35  Nº 5  2015  págs. 1590 - 96
BACKGROUND & AIMS: Radioembolization may rarely induce liver disease resulting in a syndrome that is similar to veno-occlusive disease complicating bone marrow transplantation where inflammation, endothelial cell activation and thrombosis are likely involved. We hypothesized that similar mechanisms could be implicated in radioembolization-induced liver disease (REILD). Moreover, lobar radioembolization may induce hypertrophy of the non-treated hemiliver most probably by inducing liver regeneration. METHODS: In patients with hepatocellular carcinoma, we prospectively studied serum levels of markers of liver regeneration, oxidative stress, pro-inflammatory pathways, endothelial activation and coagulation parameters over 2 months after radioembolization. RESULTS: Although REILD did not occur among 14 treated patients, a decrease in effective liver blood flow was observed. Radioembolization was followed by a persistent increase in pro-inflammatory (interleukin 6 and 8) and oxidative stress (malondyaldehide) markers, an induction of endothelial injury markers (vW factor and PAI-1) and an activation of the coagulation cascade (factor VIII, PAI-1, D-Dimer) as well as a significant increase in factors related to liver regeneration (FGF-19 and HGF). CONCLUSION: Radioembolization activates liver regeneration, produces oxidative stress, activates inflammatory cytokines and induces endothelial injury with partial activation of the coagulation cascade. These findings may have implicati
Autores: Restituto, Patricia; et al.
ISSN 0009-9120  Vol. 47  Nº 18  2014  págs. 272-8
This study shows that OPG may potentially be a biomarker for cardiovascular risk/damage in the MS and identifies adipose tissue as a potential source of OPG.
Autores: Restituto, Patricia; Monreal, José Ignacio; et al.
ISSN 0021-972X  Vol. 98  Nº 11  2013  págs. E1740 - E1748
Context: Bone turnover markers (BTMs) may identify changes in bone remodeling within a relatively short time interval before changes in bone mineral density can be detected. New markers such as osteoprotegerin, receptor activator of nuclear factor-B ligand, and sclerostin have emerged, but there is little information about their potential use in clinical practice. Design, Patients, and Setting: We performed an observational prospective study in pre-and postmenopausal ambulatory women (n =72 and n =152, respectively). Intervention: Postmenopausal women with osteoporosis (n =18) were treated with risedronate and calcium. Womenfilled out a questionnaire and underwent bone mineral density measurement using dual-energy x-ray absorptiometry at the time of enrollment and after 1 year of follow-up. BTMs were measured at baseline, at 6 months, and after 1 year. Results: Increased levels of N-terminal propeptide of type 1 procollagen (P1NP) and beta-type I collagen telopeptides (CTXs) were associated with low bone mineral density in the premenopausal (P =.02 and P =.04, respectively) and postmenopausal (P =.03 and P =.02) groups. The best analytical performance to diagnose osteoporosis was for = -CTX, osteocalcin, and P1NP, with areas under the curve of 0.70 (P =.005), 0.64 (P =.048), and 0.71 (P =.003). A significant decrease was found in P1NP, osteocalcin, tartrate-resistant acid phosphatase-5b, =-CTX, and bone alkaline phosphatase after 1 year of treatment (all P =.05). Conclusions: Our data suggest that measurement of beta beta-CTX and P1NP shows adequate analytical performance and could potentially be included in algorithms for the screening of osteoporosis. Furthermore, these two markers, along with osteocalcin and tartrate-resistant acid phosphatase5b, are useful to monitor the response to risedronate.
Autores: Ravassa, S; Beloqui, Óscar; Varo, N; et al.
ISSN 0263-6352  Vol. 31  Nº 3  2013  págs. 587 - 594
Objectives: Cardiotrophin-1 (CT-1) induces hypertrophic growth and contractile dysfunction in cardiomyocytes. This cross-sectional study was aimed to analyze CT-1 associations with echocardiographically assessed left ventricular systolic properties taking into account the influence of left ventricular growth [i.e. left ventricular hypertrophy (LVH) and inappropriate left ventricular mass (iLVM)] in asymptomatic hypertensive patients. Methods: Serum CT-1 was measured by ELISA in 278 asymptomatic hypertensive patients with a left ventricular ejection fraction more than 50% and in 25 age and sex-matched normotensive patients. Results: Serum CT-1 was increased in hypertensive patients as compared to normotensive patients. CT-1 was directly correlated with parameters of left ventricular mass (LVM) and inversely correlated with parameters assessing myocardial systolic function and left ventricular chamber contractility in hypertensive patients, these associations being independent of a number of potential confounding factors. Interestingly, the associations of CT-1 with myocardial systolic function were independent of LVM even in patients with LVH or iLVM. In addition, there was a significant increment of serum CT-1 in hypertensive patients with LVH or iLVM, especially in those in whom LVH or iLVM were accompanied by impaired myocardial systolic function, as compared to the remaining hypertensive patients and normotensive patients. Plasma amino-terminal pro-brain natriuretic peptide was not correlated with any of the assessed left ventricular systolic parameters in either group of patients. Conclusion: These findings suggest that serum CT-1 is associated with myocardial systolic dysfunction in asymptomatic hypertensive patients, independently of LVM, even in those patients with pathologic left ventricular growth.
Autores: Pinto, Victor; Casanova, Ciro; Müllerova, Hana; et al.
ISSN 1465-993X  Vol. 13  Nº 1  2012  págs. 71
Background: The relationship between serum biomarkers and clinical expressions of COPD is limited. We planned to further describe this association using markers of inflammation and injury and repair. Methods: We studied lung function, comorbidities, exercise tolerance, BODE index, and quality of life in 253 COPD patients and recorded mortality over three years. Serum levels of Interleukins 6,8 and 16, tumor necrosis factor alpha (TNF alpha) [inflammatory panel], vascular endothelial growth factor (VEGF), and matrix metalloproteinase 9 (MMP-9)[injury and repair panel] and pulmonary and activation-regulated chemokine (PARC/CCL-18) and monocyte chemotactic protein 1 (MCP-1/CCL2) [chemoattractant panel] were measured. We related the pattern of the biomarker levels to minimal clinically important differences (MCID) using a novel visualization method [ObServed Clinical Association Results (OSCAR) plot]. Results: Levels of the inflammatory markers IL-6, TNF alpha were higher and those of injury and repair lower (p < 0.01) with more advanced disease (GOLD 1 vs. 4). Using the OSCAR plot, we found that patients in the highest quartile of inflammatory and lowest quartile of injury and repair biomarkers level were more clinically compromised and had higher mortality (p < 0.05). Conclusions: In COPD, serum biomarkers of inflammation and repair are distinctly associated with important clinical parameters and survival.
Autores: Gállego, Jaime; Irimia, Pablo; Martínez Vila, E.; et al.
ISSN 0091-2751  Vol. 40  Nº 8  2012  págs. 479 - 485
Background. The assessment of carotid intima-media thickness (CIMT) may improve cardiovascular risk prediction. The optimal protocol for CIMT measurement is unclear. CIMT may be measured in the common carotid artery (CCA), carotid bifurcation (CB), and internal carotid artery (ICA), but measurements from CB and ICA are more difficult to obtain. We studied the influence of body mass index (BMI) and atheroma plaques on the capacity to obtain CIMT measurements at different carotid sites. Methods. Using an automatic system, CIMT was measured in 700 subjects aged 4575, in the near and far walls of CCA, CB, and ICA bilaterally. The presence of atheroma plaques, BMI and vascular risk factors were recorded. Results. CIMT measurements in CCA were possible in all except one subject. It was not possible to obtain CIMT measurements at CB or ICA in 24.1% of normal weight and 58.8% of obese subjects. The likelihood of obtaining CIMT measurement at all carotid sites decreased as the BMI increased. Atheroma plaques in a carotid segment did not preclude CIMT measurement at this site. Conclusions. CIMT measurements in distal carotid segments are more challenging in obese subjects. Measuring CIMT at CCA remains feasible in obese subjects and should be the primary endpoint in these subjects. Nevertheless, CB and ICA measurements, when feasible, would improve risk classification.
Autores: Roncal, Carmen; calvayrac, o; et al.
Revista: Arteriosclerosis, thrombosis and vascular biology (Print)
ISSN 1079-5642  Vol. 32  Nº 6  2012  págs. 1477 - 1487
Autores: Lorente, L; Martin, M; Varo, N; et al.
Revista: Critical care medicine
ISSN 0090-3493  Vol. 15  Nº 2  2011  págs. 1 - 8
Autores: Córdoba, Elizabeth; Baz, Rebeca; De Torres, Juan P; et al.
Revista: B M C Medical Genetics-(BioMed Central Ltd.)
ISSN 1471-2350  Vol. 12  2011  págs. 132
Autores: Varo, N; Mugueta, Carmen; et al.
Revista: Nutricion Hospitalaria
ISSN 0212-1611  Vol. 26  Nº 1  2011  págs. 144 - 151
Autores: de Torres, Juan Pablo; Casanova, C.; Pinto-Plata, V.; et al.
Revista: PLoS One
ISSN 1932-6203  Vol. 6  Nº 1  2011  págs. e1602
Autores: Missiou, A; Köstlin, K; Varo, N; et al.
Revista: Circulation
ISSN 0009-7322  Vol. 121  Nº 18  2010  págs. 2033 - 2044
Autores: Restituto, Patricia; Colina, María Inmaculada; Varo, José Javier; et al.
Revista: American journal of physiology: endocrinology and metabolism
ISSN 0193-1849  Vol. 298  Nº 5  2010  págs. 1072 - 1077
Autores: Missiou, A; Rudolf, P; Stachon, P; et al.
Revista: Circulation Research
ISSN 0009-7330  Vol. 107  Nº 6  2010  págs. 757 - 766
Autores: Moreno, MU; Beloqui, Óscar; et al.
ISSN 0263-6352  Vol. 28  Nº 11  2010  págs. 2219 - 2226
Autores: Missiou, A; Wolf, D; Platzer, I; et al.
Revista: Thrombosis and haemostasis
ISSN 0340-6245  Vol. 103  Nº 4  2010  págs. 788 - 796
Autores: Stachon, P; Missiou, A; Walter, C; et al.
Revista: PLoS One
ISSN 1932-6203  Vol. 5  Nº 7  2010  págs. e11589
Autores: Salgado, Josefa; González, Álvaro; Alegre, Estíbaliz; et al.
Libro:  Principios de bioquímica clínica y patología molecular
2014  págs. 341-346
Complejo de glucoproteínas asociadas con la distrofina, distrofias musculares de Duchenne y Becker, técnicas bioquímicas diagnósticas de las distrofias musculares de Duchenne y Becker, otras distrofias.
Autores: González, Álvaro; Alegre, Estíbaliz; Monreal, José Ignacio; et al.
Libro:  Principios de bioquímica clínica y patología molecular
2014  págs. 347-353
Cadena respiratoria mitocondrial y fosforilación oxidativa, ADN mitocondrial, origen de las proteínas mitocondriales, alteraciones del ADN mitocondrial y envejecimiento, enfermedades mitocondriales o citopatías mitocondriales, estudio bioquímico general de las citopatías mitocondriales.
Autores: Salgado, Josefa; González, Álvaro; Alegre, Estíbaliz; et al.
Libro:  Principios de bioquímica clínica y patología molecular
2014  págs. 275 - 285
Desarrollo tumoral, marcadores tumorales, determinación de los marcadores tumorales, principales marcadores tumorales séricos, aplicación de los marcadores tumorales farmacogenómica y farmacogenética.
Autores: Mugueta, Carmen; Varo, N;
Libro:  Fundamentos de Nutrición y Dietética. Bases metodológicas y aplicaciones
2011  págs. 251 - 255
Autores: Varo, N; Mugueta, Carmen;
Libro:  Fundamentos de Nutrición y Dietética. Bases metodológicas y aplicaciones
2011  págs. 263 - 267