A Clerico

Fondazione Toscana Gabriele Monasterio, Pisa, Tuscany, Italy

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Publications (320)910.92 Total impact

  • Clinical chemistry and laboratory medicine : CCLM / FESCC. 11/2014;
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    ABSTRACT: Renin-angiotensin-aldosterone system (RAAS), participated by kidney, liver, vascular endothelium, and adrenal cortex, and counter-regulated by cardiac endocrine function, is a complex endocrine system regulating systemic functions, such as body salt and water homeostasis and vasomotion, in order to allow the accomplishment of physiological tasks, such as orthostasis, physical and emotional stimuli, and to react towards the hemorrhagic insult, in tight conjunction with other neurohormonal axes, namely the sympathetic nervous system, the endothelin and vasopressin systems. The systemic as well as the tissue RAAS are also dedicated to promote tissue remodeling, particularly relevant after damage, when chronic activation may configure as a maladaptive response, leading to fibrosis, hypertrophy and apoptosis, and organ dysfunction. RAAS activation is a fingerprint of systemic arterial hypertension, kidney dysfunction, vascular atherosclerotic disease, and is definitely an hallmark of heart failure, which rapidly shifts from organ disease to a disorder of neurohormonal regulatory systems. Chronic RAAS activation is an indirect or direct target of most effective pharmacological treatments in heart failure, such as beta-blockers, inhibitors of angiotensin converting enzyme, angiotensin receptor blockers, direct renin inhibitors, and mineralocorticoid receptor blockers. Biomarkers of RAAS activation are available, with different feasibility and accuracy, such as plasma renin activity, renin, angiotensin II, and aldosterone, which all accompany the increasing clinical severity of heart failure disease, and are well recognized prognostic factors, even in patients with optimal therapy. Polymorphisms influencing the expression and activity of RAAS pathways have been recognized as clinically relevant biomarkers, likely influencing either the individual clinical phenotype, or the response to drugs. This solid, growing evidence strongly suggests the rationale for the use of biomarkers of the RAAS activation, as a guide to tailor individual therapy in the current practice, and their implementation as a rule-in marker for future trials on novel drugs in the heart failure setting. Copyright © 2014 Elsevier B.V. All rights reserved.
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    ABSTRACT: Abstract The lack of interchangeable laboratory results and consensus in current practices has underpinned greater attention to standardization and harmonization projects. In the area of method standardization and harmonization, there is considerable debate about how best to achieve comparability of measurement for immunoassays, and in particular heterogeneous proteins. The term standardization should be used only when comparable results among measurement procedures are based on calibration traceability to the International System of Units (SI unit) using a reference measurement procedure (RMP). Recently, it has been promoted the harmonization of methods for many immunoassays, and in particular for thyreotropin (TSH), as accepted RMPs are not available. In a recent paper published in this journal, a group of well-recognized authors used a complex statistical approach in order to reduce variability between the results observed with the 14 TSH immunoassay methods tested in their study. Here we provide data demonstrating that data from an external quality assessment (EQA) study allow similar results to those obtained using the reported statistical approach.
    Clinical chemistry and laboratory medicine : CCLM / FESCC. 09/2014;
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    ABSTRACT: Aim of this study is to determine the 99th upper-reference limit (URL) for cardiac troponin T (cTnT) in Italian apparently healthy subjects.
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    ABSTRACT: Ventricular remodeling occurs progressively in untreated patients after large myocardial infarction and in those with cardiomyopathy. The pathologic changes of increased left ventricular (LV) volume and perturbation in the LV chamber geometry involves not only the myocytes, but also non-myocyte cells and the extracellular matrix. Inflammation, fibrosis, neuro-hormonal activation, and ongoing myocardial damage are the mechanisms underlying remodeling. The detection of an ongoing remodeling process by means of biomarkers such as cytokines, troponins, neurohormones, metalloproteinases, galectin-3, ST-2 and others, may hold clinical value and could, to some extent, drive the therapeutical strategy in patients after a myocardial infarction or with heart failure. For this reason, there is an increasing interest in the development of new biomarkers and a great number of laboratory tests have been recently proposed, whose clinical usefulness, however, is not fully established yet.
    Clinica Chimica Acta 09/2014; · 2.85 Impact Factor
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    International journal of cardiology. 08/2014;
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    ABSTRACT: Diagnosis of heart failure (HF) is not based on a single test, but on a combination of history, physical examination and appropriate investigations. For these reasons, the accuracy of diagnosis by clinical means alone is often inadequate, especially in the early, asymptomatic stages of the HF. Thus, there is an increasing interest in the development of new cardiovascular biomarkers and, consequently, a great number of laboratory tests have recently been proposed for their assay. The aim of this article is to provide a general overview on the biomarkers, recommended by international guidelines, for the diagnosis, risk stratification, and follow-up of patients with HF. Cardiac natriuretic peptides and in particular the B-type related peptides, which are considered to be the first line biomarker for HF by international guidelines, will be discussed with special emphasis.
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    ABSTRACT: The measurement of free cortisol would be preferable with respect to the total hormone content, since it yields more reliable information about the plasma levels of the biologically active cortisol. We have developed a new method for the determination of the apparent free plasma cortisol concentration (AFCC) by means of direct radioimmunological measurement of dialyzed cortisol. The AFCC was measured in 23 plasma pools obtained from normal pregnant women at various gestational times and in 18 nonpregnant women. The mean AFCC was 19.5 +/- 7.1 ng/ml in pregnant women and 9.0 +/- 6.2 ng/ml in nonpregnant women (p less than 0.005). The percent of free cortisol (%FC) showed a progressive increase during pregnancy reaching the lower limits of the normal range at the third trimester. However, the mean of %FC was significantly lower (p less than 0.005) in pregnant women than in nonpregnant women. Our data show a progressive increase of biologically active cortisol during pregnancy.
    Journal of endocrinological investigation 04/2014; 3(2):185-7. · 1.65 Impact Factor
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    ABSTRACT: Abstract Although the perioperative event rate has declined over the past 30 years, as a consequence of the developments in anesthesiology and surgical techniques, perioperative cardiovascular complications are still a significant clinical problem. At the end of the last century, a pooled analysis of several large studies found a 30-day incidence of cardiac events of 2.5% in unselected patients aged >40 years. The identification of myocardial injury after non-cardiac surgery is a problematic and tough challenge, since up to 50% of cardiac deaths actually occur in patients with no history of overt heart disease. Recently, among novel sensitive and specific cardiovascular risk markers, the European Society of Cardiology and European Society of Anesthesiology guidelines for preoperative cardiac risk assessment have recommended that preoperative brain natriuretic peptide (BNP) or N-terminal fragment of proBNP (NT-proBNP) measurement should be considered in high-risk patients undergoing non-cardiac surgery. However, several recent studies and meta-analyses, published in the last 5 years, strongly support the use of both assays of cardiac B-type natriuretic peptides and troponins, for risk stratification in patients undergoing non-cardiac surgery, in order to improve operative and postoperative outcome. Indeed, an increase in specific cardiac biomarkers, as it is the case for natriuretic peptides and troponins, always indicates that the heart is under a stress condition or even actually injured, respectively. In conclusion, the authors suggest that future guidelines on cardiovascular risk evaluation in patients undergoing major surgical procedures should take into account the following evidence.
    Clinical Chemistry and Laboratory Medicine 02/2014; · 3.01 Impact Factor
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    ABSTRACT: The aim of this article is to review the diagnostic and prognostic relevance of measurement of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in pediatric patients with heart failure caused by various acquired and congenital heart diseases (CHD). In January 2013, we performed a computerized literature search in the National Library of Medicine (PubMed access to MEDLINE citations; http://www.ncbi.nlm.nih.gov/PubMed/ ). The search strategy included a mix of Medical Subject Headings and free-text terms for the key concepts, starting from BNP assay and 'NT-proBNP assay', children, CHD. The search was further refined by adding the keywords neonate/s, newborn/s, heart failure, cardiomyopathy, screening, prognosis, follow-up, and management. BNP values are age and method dependent, even in pediatric populations. Regardless of age, there is great variability in BNP/NT-proBNP values within CHD characterized by different hemodynamic and clinical conditions. There is enough evidence to support the use of BNP/NT-proBNP as an adjunctive marker in the integrated evaluation of patients with congenital and acquired heart disease to help define severity and progression of heart failure as well in the monitoring of response to treatment. BNP/NT-proBNP can also be used for the screening of heart failure and as a prognostic marker in children undergoing cardiac surgery; however, to date, there are studies with heterogeneous patient groups, and diverse outcome measures selected are still few. BNP/NT-proBNP can be used as adjunctive markers in the integrated screening, diagnosis, management, and follow-up of children with heart failure caused by various acquired and congenital heart disease.
    Heart Failure Reviews 01/2014; · 4.45 Impact Factor
  • The Journal of thoracic and cardiovascular surgery 01/2014; 147(1):541. · 3.41 Impact Factor
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    ABSTRACT: Background There is strong clinical and experimental evidence that altered thyroid homeostasis negatively affects survival in cardiac patients, but a negative effect of the low triiodothyronine (T3) syndrome on the outcome of coronary artery bypass grafting (CABG) has not been demonstrated. This study was designed to evaluate the prognostic significance of low T3 syndrome in patients undergoing CABG. Methods The thyroid profile was evaluated at hospital admission in 806 consecutive CABG patients. Known thyroid disease, severe systemic illness, and use of drugs interfering with thyroid metabolism were considered exclusion criteria. The effect of the baseline free T3 (fT3) concentration and of preoperative low T3 syndrome (fT3 <2.23 pmol/L) on the risk of low cardiac output (CO) and death was analyzed in a logistic regression model. Results There were 19 (2.3%) deaths, and 64 (7.8%) patients experienced major complications. After univariate analysis, fT3, low T3, New York Heart Association class greater than II, low left ventricular ejection fraction (LVEF), and emergency were associated with low CO and hospital death. History of atrial fibrillation, cardiopulmonary bypass time, and peripheral vascular disease were associated only with low CO. At multivariate analysis, only fT3, low T3, emergency, and LVEF were associated with low CO, and fT3 (odds ratio, 0.172, 95% confidence interval, 0.078 to 0.379; p < 0.0001) and LVEF (odds ratio, 0.934, 95% confidence interval, 0.894 to 0.987; p = 0.03) were the only independent predictors of death. Conclusions Our study demonstrates that low T3 is a strong predictor of death and low CO in CABG patients. For this reason, the thyroid profile should be evaluated before CABG, and patients with low T3 should be considered at higher risk and treated accordingly.
    The Annals of thoracic surgery 01/2014; · 3.45 Impact Factor
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    ABSTRACT: The natriuretic peptide (NP) family includes atrial (ANP), brain or B-type (BNP) and C-type NP (CNP). A huge number of experimental and clinical studies, published in the 1st decade of this century, have added further support to the hypothesis that endocrine function in the human heart is a relevant component of a complex network including endocrine, nervous and immune systems. The NP hormones constitute a well-integrated regulatory system and share a similar spectrum of biological actions, although there are some differences in biological potency between ANP, BNP and CNP. However, several important issues on this field need to be investigated further. The production, secretion and peripheral degradation pathways of both BNP and CNP should be clarified in detail. In particular, the hypothesis that the circulating plasma pool of the prohormone can function as a precursor of the active peptide hormone should be demonstrated definitively. Recent findings indicate that peripheral processing of circulating prohormones could likely be submitted to regulatory rules, which might be impaired in patients with heart failure, opening up new perspectives even in the treatment of heart failure. This hypothesis suggests a novel pharmacological target for drugs inducing and/or modulating the maturation of the prohormone into active hormone. © 2014 S. Karger AG, Basel.
    Frontiers of hormone research 01/2014; 43:134-43. · 1.24 Impact Factor
  • Journal of the American College of Cardiology 12/2013; · 14.09 Impact Factor
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    ABSTRACT: The high prevalence of obesity in children may increase the magnitude of lifetime risk of cardiovascular disease (CD). At present, explicit data for recommending biomarkers as routine pre-clinical markers of CD in children are lacking. C-type natriuretic peptide (CNP) is assuming increasing importance in CD; in adults with heart failure, its plasma levels are related to clinical and functional disease severity. We have previously reported five different reference intervals for blood CNP as a function of age in healthy children; however, data on plasma CNP levels in obese children are still lacking. Aim of this study was to assess CNP levels in obese adolescents and verify whether they differ from healthy subjects. Plasma CNP was measured in 29 obese adolescents (age:11.8±0.4 years; BMI=29.8±0.82) by radioimmunoassay and compared with the reference values of healthy subjects. BNP was also measured. Both plasma CNP and BNP levels were significantly lower in the obese adolescents compared to the appropriate reference values (CNP:3.4±0.2 vs 13.6±2.3pg/ml, p<0.0001; BNP:18.8±2.6 vs 36.9±5.5pg/ml, p=0.003). There was no significant difference between CNP values in males and females. As reported in adults, we observed lower plasma CNP and BNP levels in obese children, suggesting a defective natriuretic peptide system in these patients. An altered regulation of production, clearance and function of natriuretic peptides, already operating in obese adolescents, may possibly contribute to the future development of CD. Thus, the availability of drugs promoting the action of natriuretic peptides may represent an attractive therapeutic option to prevent CD.
    Peptides 10/2013; · 2.52 Impact Factor
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    ABSTRACT: Background: Results collected from the 2010-2012 cycles of the 'Immunocheck' external quality assessment scheme for 25-hydroxyvitamin D, conducted by QualiMedLab CNR (Italy) and ProBioQual (France; 250 among Italian and French laboratories) are presented in this article. Methods: Details of how QualiMedLab operates can be found in QualiMedLab website. Results: Interlaboratory imprecision was 19 (2010), 15 (2011) and 13% (2012). The LIAISON(®) analyzer (DiaSorin, Italy) was the most utilized, followed by Roche (UK), ImmunoDiagnostic Systems methods (UK), ARCHITECT (Abbott, IL, USA), radioimmunoassay (DiaSorin) and others. The within-method variability between laboratories (percentage coefficient of variation) were 15, 12.7 versus 9.8% for LIAISON, 27.8, 16.5 versus 11.7% for Roche, 15, 12 versus 17% for ImmunoDiagnostic Systems and 17.4, 18.6 versus 17.5% for radioimmunoassay in the 2010, 2011 versus 2012 cycles, and 15 versus 8.9% for ARCHITECT in the 2011 versus 2012, respectively. Conclusion: Significant differences in specific samples and discrepancies between laboratories and methods still exist, making the actuation of appropriate external quality assessment schemes mandatory.
    Biomarkers in Medicine 10/2013; 7(5):691-9. · 3.22 Impact Factor
  • Journal of the American College of Cardiology 09/2013; · 14.09 Impact Factor
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    ABSTRACT: Since the discovery of the influence of the endocrine system on cardiac endocrine function 30 years ago, an increasing number of experimental and clinical studies have consolidated endocrine function of human heart as being a relevant component of a complex network including endocrine, nervous and immune systems. Many aspects, however, still remain unclear as to the production, secretion and peripheral degradation pathways of B- and C-type natriuretic peptides. In particular, the hypothesis that the circulating plasma pool of the pro-hormone can function as precursor of the active peptide hormone is yet to be fully demonstrated. According to recent studies, peripheral processing of circulating pro-hormone likely undergoes regulation pathways which seem to be impaired in patients with heart failure. This would open new perspectives also in the treatment of heart failure, and identify novel pharmacological targets for drugs inducing and/or modulating the maturation of the pro-hormone into active hormone.
    Pharmacological Research 08/2013; · 4.35 Impact Factor
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    ABSTRACT: Abstract The purpose of this document is to develop recommendations on the use of the latest generation of cardiac troponins in emergency room settings for the diagnosis of myocardial infarction in patients with suspected acute coronary syndrome (ACS) without persistent ST-segment elevation (NSTE-ACS). The main points which have been addressed reaching a consensus are represented by: Suitability and appropriateness of the terminology. Appropriateness of the request. Confirmation of the diagnosis of myocardial infarction (rule-in). Exclusion of the diagnosis of myocardial infarction (rule-out). Work method: Each point has been analyzed by taking into account the evidence presented in medical publications. Recommendations were developed using the criteria adopted by the European Society of Cardiology and the American Heart Association/American College of Cardiology (www.escardio.org/guidelines). Each point of the recommendation was submitted for validation to an external audit by a Group of Experts (named above).
    Clinical Chemistry and Laboratory Medicine 07/2013; · 3.01 Impact Factor
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    ABSTRACT: Recent studies suggested that there are marked systematic differences among BNP immunoassays. In this study we compared the BNP data and clinical results obtained with different immunoassays, including a new method (ST-AIA-PACK, TOSOH Corporation). BNP was measured on plasma-EDTA samples of healthy subjects (HS, n=126) and patients with heart failure (HF, n=31 NYHA I, II; n=46 NYHA III, IV) using the ST-AIA-PACK and the Triage Biosite (Beckman Coulter) methods. Control samples distributed in the CardioOrmoCheck external quality assessment were also measured with TOSOH and the most used BNP immunoassays in Italy. TOSOH method showed a good correlation (R=0.976; n=327) but a mean bias (-46.9%) compared to Triage Biosite. On the base of the results obtained in 10 samples of the CardioOrmoCheck study, TOSOH method showed a strict agreement with ADVIA Centaur, while it underestimated BNP in comparison with Triage (-52.5%) and ARCHITECT methods (-39.4%). The agreement of ST-AIA-PACK and Triage Biosite methods for classification of HF patients was tested using 100 ng/L of BNP; the positive agreement between methods was 65%, overall agreement was 73%. Our results confirm that there are marked differences in measured values among commercial methods for BNP assay.
    Clinica chimica acta; international journal of clinical chemistry 07/2013; · 2.54 Impact Factor

Publication Stats

3k Citations
910.92 Total Impact Points


  • 2008–2014
    • Fondazione Toscana Gabriele Monasterio
      Pisa, Tuscany, Italy
  • 2003–2014
    • Scuola Superiore Sant'Anna
      Pisa, Tuscany, Italy
  • 2013
    • The Children’s Hospital at Montefiore (CHAM)
      New York City, New York, United States
  • 1986–2013
    • National Research Council
      • Institute of Clinical Physiology IFC
      Roma, Latium, Italy
  • 2007–2008
    • Scuola Normale Superiore di Pisa
      Pisa, Tuscany, Italy
  • 1979–2006
    • Università di Pisa
      • Department of Clinical and Experimental Medicine
      Pisa, Tuscany, Italy
  • 2004
    • Università degli Studi di Brescia
      Brescia, Lombardy, Italy
  • 1998
    • Charles University in Prague
      • 1. lékařská fakulta
      Praha, Hlavni mesto Praha, Czech Republic
  • 1995
    • University of Ferrara
      Ferrare, Emilia-Romagna, Italy