Melania Puddu

Università degli studi di Cagliari, Cagliari, Sardinia, Italy

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Publications (36)58.32 Total impact

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    ABSTRACT: Neonatal sepsis still remain a major cause of morbidity and mortality in neonatal intensive care unit (NICU). Recently, soluble CD14 subtype (sDC14-ST) also named presepsin, was proposed as an effective biomarker for diagnosing, monitoring, and assessing the risk of neonatal sepsis and septic shock. The aim of this study was to investigate the diagnostic accuracy of sCD14-ST presepsin in diagnosing neonatal bacterial sepsis and in discriminating non-bacterial systemic inflammatory response syndrome (SIRS) from bacterial sepsis. This study involved 65 critically ill full-term and preterm newborns admitted to the neonatal intensive care unit (NICU), divided into three groups: 25 newborns with bacterial neonatal sepsis (group A); 15 newborns with a diagnosis of non-bacterial SIRS and with no localizing source of bacterial infection (group B); 25 babies with no clinical or bacteriological signs of systemic or local infection receiving routine NICU care, most of them treated with phototherapy for neonatal jaundice (group C). A total of 102 whole blood samples were collected, 40 in group A, 30 in group B and 32 in group C. In 10 babies included in group A, sCD14-ST presepsin was also measured in an additional second blood sample collected 3days after the start of antibiotic treatment. sCD14-ST presepsin was measure by a commercially available chemiluminescent enzyme immunoassay (CLEIA) optimized on an automated immunoassay analyzer. Statistical analysis was performed by means of MedCalc® statistical package; receiver operating characteristic (ROC) analysis was computed, and the area under the ROC curve (AUC) was used to evaluate the ability of sCD14-ST to discriminate neonatal bacterial sepsis from non-bacterial SIRS. Blood sCD14-ST presepsin levels were found significantly higher in bacterial sepsis when compared with controls (p<0.0001); similarly, they were higher in non-bacterial SIRS when compared with controls (p<0.0001). However, no statistically significant difference was found between bacterial sepsis and non-bacterial SIRS (p=0.730). In our population, CRP and sCD14-ST did not correlate each other. ROC analysis revealed that sCD14-ST presepsin has an area under the curve (AUC) of 0.995 (95%C.I.: 0.941-1.00) greater than that of CRP (0.827; 95% C.I.: 0.72-0.906). Similarly, in the group of babies with non-infectious SIRS, sCD14-ST AUC was greater than CRP AUC (0.979; 95% C.I.: 0.906-0.999 versus 0.771; 95% C.I.: 0.647-0.868). In controls, preliminary reference intervals for sCD14-ST ranged 223.4-599.7ng/L, being significantly different from those previously published elsewhere. In conclusion, sCD14-ST presepsin could be introduced in clinical practice as a diagnostic tool for improving the management of neonatal sepsis and non-bacterial SIRS. Copyright © 2015. Published by Elsevier B.V.
    Clinica chimica acta; international journal of clinical chemistry 07/2015; DOI:10.1016/j.cca.2015.07.025 · 2.76 Impact Factor
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    ABSTRACT: The aim of this study was to better define, by immunohistochemistry, the molecular markers of renal stem/progenitor cells localized in the different niches of ten human preterm kidneys with gestational age ranging from 11 up to 25 weeks. Our data evidence the existence of multiple stem/progenitor pools in different zones of the human developing kidney that are characterized by different phenotypes: capsular stem cells were EMA (MUC1)+, MDM2+, Vimentin+ and Wnt1+; progenitors of the sub-capsular nephrogenic zone were MDM2+ and Wnt1+; cap mesenchymal cells were EMA (MUC1)+, CD15+, vimentin+, Wt1+, CD10+, Bcl2+, Wnt1+ and PAX2+; interstitial progenitor cells were Vimentin+, Wt1+ and α1Anti-tripsin+. Our data evidence the existence of multiple stem/progenitor cell pools in the fetal and neonatal human kidney. Progenitors of these different pools are characterized by a peculiar phenotype, indicating a different differentiation stage of these renal progenitors. A better knowledge of the molecular markers expressed by renal stem/progenitors might represent a relevant datum for researchers involved in renal regenerative medicine. Copyright © 2015 Elsevier GmbH. All rights reserved.
    Acta histochemica 03/2015; 117(4-5). DOI:10.1016/j.acthis.2015.02.014 · 1.76 Impact Factor
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    ABSTRACT: With the incidence of end-stage renal disease increasing dramatically during the last ten years, its prevalence rising about 8% per year, chronic kidney disease (CKD) represents one of the most problematic public health problems worldwide. CKD represents a growing clinical problem that, in its terminal stages, requires renal replacement therapy. Kidney transplant has been proposed as the definitive therapy able to address the growing clinical, social and economic problems related to the increasing prevalence of end-stage kidney disease (ESKD). Traditional stem cell-based regenerative medicine, when applied to kidneys disrupted by end-stage renal disease, has been shown to be unable to regenerate the damaged organ. The theme of this work is to hypothesize a new approach to the prevention of CKD, based on the management of the huge amount of stem/progenitor cells physiologically present in the kidney of preterm babies at birth. Here a new concept of primary prevention of renal disease is suggested: a true primary prevention, starting in the perinatal period aimed at increasing the number of functioning glomeruli. This approach has been defined as "physiological regenerative medicine", in order to underline the use of physiological tools, including endogenous renal stem cells and stem cell stimulators physiologically expressed in our cells. Copyright © 2015. Published by Elsevier B.V.
    Clinica Chimica Acta 02/2015; 444. DOI:10.1016/j.cca.2015.02.023 · 2.82 Impact Factor
  • Italian Journal of Pediatrics 10/2014; 40(Suppl 2):A14-A14. DOI:10.1186/1824-7288-40-S2-A14 · 1.52 Impact Factor
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    ABSTRACT: Objective: In the present review article we have summarized the use of the metabolomics approach to study the metabolic modifications occurring in several bio-fluids due to viral infections. The aim is to highlight the ability of metabolomics to find early fingerprints, which are related to the infections. Methods: The H-1-NMR, UHPLC/MS/MS 2, UPLC/ESI-SYNAPT-HDMS, UPLC-Q-TOF-HDMS analyses were used for the determination of several metabolites representative of the viral infections. The data were analyzed by Principal Component Analysis (PCA), Partial Least Square Discriminant Analysis (PLS-DA) and by regression techniques. Results: The major changes were related to nucleotide, carbohydrates, lipids and amino acid metabolisms. Conclusions: The metabolomics approach could be considered a viable option for characterization of the viral infection and for detecting on going differences in the bio-fluids composition.
    Journal of Maternal-Fetal and Neonatal Medicine 10/2014; 27 Suppl 2(S2):53-7. DOI:10.3109/14767058.2014.955963 · 1.21 Impact Factor
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    ABSTRACT: The development of the mammalian kidney is a complex and in part unknown process which requires interactions between pluripotential/stem cells, undifferentiated mesenchymal cells, epithelial and mesenchymal components, eventually leading to the coordinate development of multiple different specialized epithelial, endothelial and stromal cell types within the kidney architectural complexity. We will describe the embryology and molecular nephrogenetic mechanisms, a fascinating traffic of cells and tissues which takes place in five stages: (1) ureteric bud (UB) development; (2) cap mesenchyme formation; (3) mesenchymal-epithelial transition (MET); (4) glomerulogenesis and tubulogenesis; (5) interstitial cell development. In particular, we will analyze the multiple cell types involved in these dramatic events as characters moving between different worlds, from the mesenchymal to the epithelial world and back, and will start to define the multiple factors that propel these cells during their travels throughout the developing kidney. Moreover, according with the hypothesis of renal perinatal programing, we will present the results reached in the fields of immunohistochemistry and molecular biology, by means of which we can explain how a loss or excess of molecular factors governing nephrogenesis may cause the onset of pathologies of different gravity, in some cases leading to a chronic kidney disease at different times from birth.
    International Urology and Nephrology 09/2014; 47(1). DOI:10.1007/s11255-014-0784-0 · 1.29 Impact Factor
  • P P Bassareo · L Saba · M Puddu · V Fanos · G G Mercuro
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    ABSTRACT: Intrauterine growth retardation and prematurity at birth constitute risk factors for future cardiovascular adverse events. Some previous reports have highlighted that subjects born preterm may develop peripheral arterial dysfunction. However, central (aortic) arterial distensibility has not yet been fully investigated in these subjects.
    International angiology: a journal of the International Union of Angiology 07/2014; · 1.01 Impact Factor
  • P.P. Bassareo · V. Fanos · M. Puddu · G. Flore · G. Mercuro
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    ABSTRACT: Background High blood levels of asymmetric dimethylarginine (ADMA) are associated with future development of adverse cardiovascular events. The ADMA/symmetric dimethylarginine (SDMA) ratio is a marker of ADMA catabolism, with a high ADMA/SDMA ratio being suggestive of reduced ADMA excretion. Aims This study aimed a) to verify the presence of a statistically significant difference between ADMA/SDMA ratio levels in a group of young adult subjects who were born preterm with an extremely low birth weight (ex-ELBW) and a group of healthy adults born at term and b) to seek correlations between ADMA/SDMA ratio levels in ex-ELBW and anthropometric and clinical parameters (gender, chronological age, gestational age, birth weight, and length of stay in the Neonatal Intensive Care Unit). Subjects, study design, outcome measures Thirty-seven ex-ELBW subjects (11 males [M] and 26 females [F], aged 17–28 years, mean age: 22.2 ± 1.8 years) were compared with 37 controls (11 M and 26 F). ADMA/SDMA ratio levels were assessed for each patient included in the study. Results ADMA/SDMA ratio in ex-ELBW subjects was higher compared to controls (1.42 ± 0.31 vs 0.95 ± 0.14, p < 0.002) and inversely correlated with birth weight (r = − 0.68, p < 0.0001) and gestational age (r = − 0.54, p < 0.0005). Conclusions ADMA catabolism is significantly decreased in ex-ELBW subjects compared to controls, underlining a probable correlation with restriction of intrauterine growth. These results suggest the onset of early circulatory dysfunction predictive of increased cardiovascular risk in ex-ELBW.
    Early human development 04/2014; 90(4). DOI:10.1016/j.earlhumdev.2014.01.010 · 1.93 Impact Factor
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    ABSTRACT: To look for differences in the urinary metabolic profile and in the hematic asymmetric dimethylarginine (ADMA) levels between a group of young adults born preterm with an extremely low birthweight (< 1,000g; ex-ELBW; n=19) and a control group of subjects born at term with a weight appropriate for their gestational age (AGA; n=13); to look for a possible correlation between the urinary metabolic profile in ex-ELBW and their hematic levels of ADMA. Urine samples were analyzed by 1H-nuclear magnetic resonance spectroscopy, and then submitted to unsupervised and supervised multivariate analysis. Samples of blood were collected and ADMA concentration was assessed by high-performance liquid chromatography. Using supervised PLS-DA (partial least squares discriminant analysis) model, the Authors were able to discriminate between ex-ELBW and AGA. Statistically significant differences were detected in the ADMA levels between ex-ELBW and AGA (p<0.02). Ex-ELBW metabolic profile correlated with ADMA concentrations (r=0.456, p<0.05). Conversely, ADMA levels in AGA did not correlated with their metabolic profiles. This study demonstrates the relevance of the metabolomic technique as a predictive tool of the metabolic status in exELBW. The relationship between ex-ELBW urinary metabolic profile and their blood ADMA levels suggests the presence of a subclinical cardio-renal involvement in these subjects.
    Clinical biochemistry 12/2013; 47(6). DOI:10.1016/j.clinbiochem.2013.11.018 · 2.28 Impact Factor
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    ABSTRACT: Metabolomics is a new analytical technique defined as the study of the complex system of metabolites that is capable of describing the biochemical phenotype of a biological system. In recent years the literature has shown an increasing interest in paediatric obesity and the onset of diabetes and the metabolic syndrome in adulthood. Some studies show that fetal malnutrition, both excessive and insufficient, may permanently alter the metabolic processes of the fetus and increase the risk of future chronic pathologies. At present then, attention is being focused mainly on the formulation of new hypotheses, by means of metabolomics, concerning the biological mechanisms to departure from fetal-neonatal life that may predispose to the development of these diseases.
    Molecules 10/2013; 18(10):11724-32. DOI:10.3390/molecules181011724 · 2.42 Impact Factor
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    ABSTRACT: Abstract Background: Prematurity at birth is a known risk factor for the development of an early chronic renal disease. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a well established biomarker of kidney injury, while high blood levels of asymmetric dimethylarginine (ADMA) are associated with the future development of adverse cardiovascular events and cardiac death. Aims: (1) to verify the presence of statistically significant differences between urinary NGAL and hematic ADMA levels in young adults born preterm at extremely low birth weight (<1000 g; ex-ELBW) and those of a control group of healthy adults born at term (C) (2) to seek correlations between NGAL and ADMA levels, which would indicate the presence of an early cardio-renal involvement in ex-ELBW. Methods: Twelve ex-ELBW subjects (six males and six female, mean age: 23.9 ± 3.2 years) were compared with 12 C (six males and six female). Urinary NGAL and hematic ADMA levels were assessed. Results: Urinary NGAL levels were higher in ex- ELBW subjects compared to C (p < 0.05), as well as hematic ADMA concentrations (p < 0.05). A statistically significant correlation was found between urinary NGAL and ADMA (r = -0.60, p < 0.04). Conclusions: Our preliminary findings support the hypothesis that in ex-ELBW subjects the development of an early chronic kidney disease contributes towards inducing an increase in the atherosclerotic process and in the risk of future adverse cardiovascular events.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 10/2013; 26 Suppl 2(S2):80-3. DOI:10.3109/14767058.2013.829698 · 1.21 Impact Factor
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    ABSTRACT: Metabolomics (or metabonomics) is based on the systematic study of the complete set of metabolites in a biological sample and is considered the most innovative of the 'omics' sciences. The metabolome is currently regarded as the 'new clinical biochemistry' it is the most predictive phenotype, through consideration of epigenetic differences. Among more than 5000 papers listed in PubMed on this topic in the last three years, less than 60 refer to neonatal life. Aim of this review is to present the clinical applications of metabolomics in neonatology, including results of recent studies performed in experimental models and newborns.
    Early human development 06/2013; 89S1:S7-S10. DOI:10.1016/S0378-3782(13)70003-3 · 1.93 Impact Factor
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    ABSTRACT: Soluble CD14 subtype (sCD14-ST), also named presepsin, is a 13 kDa truncated form of soluble CD14 (sCD14), consisting of 64 amino acid residues. Systemic inflammation and sepsis are characterized by an early, significant increase in sCD14-ST presepsin blood concentration and thus, this small polypeptide has been proposed as a novel, reliable biomarker for the management of sepsis. We enrolled twenty-six consecutive non-septic preterm newborns with gestational age (GA) between 26 and 36 weeks) admitted to NICU after the first day of life for various severe diseases. sCD14-ST presepsin was measure on whole blood samples by a rapid commercial available chemiluminescent enzyme immunoassay (CLEIA) based on a non-competitive CLEIA. The mean sCD14-ST presepsin blood level in 26 preterm newborns was 643.1 ng/L, with a standard deviation (SD) of 303.8 ng/L; the median value was 578 ng/L. Our results clearly suggest no correlation between GA and sCD14-ST presepsin blood level between 26 and 36 weeks and thus it is reasonable to adopt a unique reference range for preterm newborns.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 10/2012; 25(Suppl 5):51-3. DOI:10.3109/14767058.2012.717462 · 1.21 Impact Factor
  • Proceedings and Selected abstracts of the 3rd International Conference on Clinical Neonatology, Turin; 05/2012
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    ABSTRACT: The survival rate for extremely low birth weight (ELBW) infants born preterm is on an increasing upward trend, despite the possibility of neuro-cerebral consequences in later life. To date, scarce information is available on the effect of extreme prematurity on cardiovascular system. To verify the presence of standard echocardiographic and ECG alterations in ex-ELBW young healthy adults. A color Doppler echocardiogram and an ECG were performed on 24 ex-ELBW (4 males and 20 females; mean: 23.2 ± 3.3 years), compared with 24 healthy subjects born at term (C). ECG parameters examined: PR, QT, QT(c), and QT dispersion (QT(d)). Gestational age, birth weight, and duration of stay in neonatal intensive care unit were obtained from clinical records. Transthoracic echocardiography did not reveal differences between ex-ELBW and C, while a significant difference was displayed by ex-ELBW with regard to PR (141.5 ± 13.4 ms vs. 164.2 ± 24.0 ms, p < 0.0003), QT(c) (417.0 ± 23.6 ms vs. 369.9 ± 19.5 ms, p =0.00001), and QT(d) (30.4 ± 14.1 ms vs. 24.6 ± 8.2 ms, p < 0.00001). In two patients (8.3%), QT(c) exceeded the upper limit of normal range. A statistically significant inverse correlation was observed between QT(c) and gestational age (r = -0.67, p < 0.0003). QT(c) and QT(d) in ex-ELBW were found to be at the upper limit of normal range and correlated with gestational age and birth weight; in two cases, QT(c) exceeded the upper limit. This study, irrespective of the pathophysiological mechanism involved, underlines a potential risk for ex-ELBW of developing ventricular arrhythmias when using drugs capable of prolonging QT interval. QT(c) and QT(d) in young adults previously born preterm with an ELBW (401-1000 g) were generally found to be at the upper limit of normal range and correlated with gestational age and birth weight. This finding underlines a potential risk for ex-ELBW of developing ventricular arrhythmias when using drugs capable of prolonging QT interval.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 09/2011; 24(9):1115-8. DOI:10.3109/14767058.2010.543600 · 1.21 Impact Factor
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    ABSTRACT: Clinical metabolomics is a recent "omic" technology which is defined as a global holistic overview of the personal metabolic status (fingerprinting). This technique allows to prove metabolic differences in different groups of people with the opportunity to explore interactions such as genotype-phenotype and genotype-environment type, whether normal or pathological. To study chronic kidney injury 1) using urine metabolomic profiles of young adults born extremely low-birth weight (ELBW) and 2) correlating a biomarker of kidney injury, urinary neutrophil gelatinase-associated lipocalin (NGAL), in order to confirm the metabolomic injury profile. Urine samples were collected from a group of 18 people (mean: 24-year-old, std: 4.27) who were born with ELBW and a group of 13 who were born at term appropriate for gestational age (AGA) as control (mean 25-year-old, std: 5.15). Urine samples were analyzed by (1)H-nuclear magnetic resonance spectroscopy, and then submitted to unsupervised and supervised multivariate analysis. Urine NGAL (uNGAL) was measured using ARCHITECT (ABBOTT diagnostic NGAL kit). With a multivariate approach and using a supervised analysis method, PLS-DA, (partial least squares discriminant analysis) we could correlate ELBW metabolic profiles with uNGAL concentration. Conversely, uNGAL could not be correlated to AGA. This study demonstrates the relevance of the metabolomic technique as a predictive tool of the metabolic status of exELBW. This was confirmed by the use of uNGAL as a biomarker which may predict a subclinical pathological process in the kidney such as chronic kidney disease.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 07/2011; 24 Suppl 2(S2):40-3. DOI:10.3109/14767058.2011.606678 · 1.21 Impact Factor
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    ABSTRACT: To date, we have little knowledge on the overall metabolic status of neonates with intrauterine growth retardation (IUGR). In the last few years, the analysis of metabolomics has assumed an important clinical role in identifying "disorders" in the metabolic profile of patients. The aim of this work has been to analyze the urine metabolic profiles of neonates with IUGR and compare them with controls to define the metabolic patterns associated with this pathology. To our knowledge, this is the first study of metabolomics performed on neonates with IUGR. Recruited for the study were 26 neonates with IUGR diagnosed in the neonatal period and with weight at birth below the 10th percentile and 30 neonates of proper gestational weight at birth (controls). In the first 24 hours (prior to feeding) (T1) and about 4 days after birth (T2), a urine sample was taken non-invasively from each neonate. The samples were then frozen at -80°C up to the time of the analysis by proton nuclear magnetic resonance spectroscopy (1H-NMR). The data contained in the NMR spectra obtained from the single samples were statistically analyzed using the Principal Components Analysis and the Partial Least Squares-Discriminate Analysis. By means of a multivariate analysis of the NMR spectra obtained, it was possible to highlight the differences between the two groups (IUGRs and controls) owing to the presence of different metabolic patterns. The discriminants in the urine metabolic profiles derived essentially from significant differences in certain metabolites such as: myo-inositol, sarcosine, creatine and creatinine. The metabolomic analysis showed different urine metabolic profiles between neonates with IUGR and controls and made it possible to identify the molecules responsible for such differences.
    The journal of maternal-fetal & neonatal medicine: the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 07/2011; 24 Suppl 2(S2):35-9. DOI:10.3109/14767058.2011.605868 · 1.21 Impact Factor
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    ABSTRACT: Sporadic data present in literature report how preterm birth and low birth weight are risk factors for the development of cardiovascular diseases in later life. High levels of asymmetric dimethylarginine (ADMA), a strong inhibitor of nitric oxide synthesis, are associated with the future development of adverse cardiovascular events and cardiac death. Aims: 1) to verify the presence of a statistically significant difference between ADMA levels in young adults born preterm at extremely low birth weight (<1000 g; ex-ELBW) and those of a control group of healthy adults born at term (C) and 2) to seek correlations between ADMA levels in ex-ELBW and anthropometric and clinical parameters (gender, chronological age, gestational age, birth weight, and duration of stay in Neonatal Intensive Care Unit). Thirty-two ex-ELBW subjects (11 males [M] and 21 females [F], aged 17-29years, mean age 22.2 ± 2.3 years) were compared with 25 C (7 M and 18F). ADMA levels were assessed by high-performance liquid chromatography with highly sensitive laser fluorescent detection. ADMA levels were reduced in ex-ELBW subjects compared to C (0.606+0.095 vs 0.562+0.101 μmol/L, p<0.05), and significantly correlated inversely with gestational age (r=-0.61, p<0.00001) and birth weight (r=-0.57, p<0.0002). Our findings reveal a significant decrease in ADMA levels of ex-ELBW subjects compared to C, underlining a probable correlation with preterm birth and low birth weight. Taken together, these results may underlie the onset of early circulatory dysfunction predictive of increased cardiovascular risk.
    International journal of cardiology 03/2011; 159(3):217-9. DOI:10.1016/j.ijcard.2011.02.069 · 6.18 Impact Factor
  • Journal of Maternal-Fetal and Neonatal Medicine 10/2010; · 1.21 Impact Factor

Publication Stats

302 Citations
58.32 Total Impact Points

Institutions

  • 2008–2015
    • Università degli studi di Cagliari
      • • Department of Environmental and Life Science
      • • Department of Medical Science "Mario Aresu"
      • • Department of Biomedical Science
      Cagliari, Sardinia, Italy
    • Azienda Ospedaliera Universitaria Cagliari
      Cagliari, Sardinia, Italy