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BC: Articoli scritti da A. Padoan

Valutazione precoce del danno cardiaco da farmaci chemioterapici: importanza della misura delle troponine cardiache I e T con metodi ad alta-sensibilità analitica
High-sensitivity cardiac troponin I and T methods for the early detection of myocardial injury in patients on chemotherapy
<p>Important advances achieved in pharmacological cancer treatment have led progressively to a reduction in mortality from many forms of cancer, and increasing numbers of previously incurable patients can now hope to become cancer-free. Yet, to achieve these improved outcomes a high price has been paid in terms of untoward side effects associated with treatment, cardiotoxicity in particular. Several recent studies have reported that cardiac troponin assay using high-sensitivity methods (hs-cTn) can enable the early detection of myocardial injury related to chemotherapy or abuse of drugs that are potentially cardiotoxic. Several authors have recently suggested that changes in hs-cTn values enable the early diagnosis of cardiac injury from chemotherapy, thus potentially benefitting cancer patients with increased troponin values by initiating early cardioprotective therapy. However, large randomised clinical trials are needed in order to evaluate the cost/benefit ratio of standardised protocols for the early detection of cardiotoxicity using the hs-cTn assay in patients treated with chemotherapy.</p>
Biochimica Clinica ; 44(3) 279-286
Documenti SIBioC - SIBioC Documents
Calcolo e valutazione dei valori di riferimento della troponina cardiaca I (cTnI) misurata in un gruppo di volontari sani italiani con metodi immunometrici ad alta sensibilità: uno studio multicentrico
Establishment and evaluation of cardiac troponin I reference values measured in a group of Italian healthy volunteers using high-sensitivity methods: a multi-center study.
<p>Introduction: this study compares the cardiac troponin I (cTnI) values measured with three high-sensitivity (hs) different methods in apparently healthy volunteers enrolled in a multicenter study.<br />Methods: heparinized plasma samples were collected from 1511 volunteers in 8 Italian clinical institutions (mean age 51.5 years, SD 14.2, range 18-86, female to male ratio 0.94). All volunteers denied chronic or acute diseases and had normal values of routine laboratory tests and ECG. The reference laboratory of the study (Laboratorio Fondazione CNR Regione Toscana G. Monasterio, Pisa, Italy) assayed all plasma samples with three hs-methods: Architect hs-cTnI, Access hs-cTnIand ADVIA Centaur XPT hs-cTnI. After the exclusion of outlier values, calculation of 99th percentile (Upper Reference Limit, URL) values was performed using both robust nonparametric and bias corrected and accelerated bootstrap methods.<br />Results: large between-method differences were found. ADVIA Centaur measured higher cTnI values (up to 2-fold) than the two other methods. cTnI values were significantly higher in men than in women, and progressively increased with age over 55 years. Moreover, 99th percentile URL values also depended on the statistical approach used for calculation (robust non-parametric versusbootstrap). All 99th percentile URL values calculated with non-parametric robust method were on average slightly lower than those suggested by manufacturers (mean difference 4.2 ng/L, standard error 1.7, p=0.0273).<br />Conclusion: clinicians should be advised that plasma samples from the same patient should be measured for hs-cTnI in the same laboratory. Specific clinical studies are needed to establish the most appropriate statistical approach to calculate 99th percentile URL values for hs-cTnI methods.</p>
Biochimica Clinica ; 44(2) S032-S047
Contributi Scientifici - Scientific Papers
La misura combinata dei biomarcatori cardio-specifici è utile nei pazienti con sospetto di malattie cardiovascolari
The combined measurement of cardio-specific biomarkers is a useful tool in patients with suspected cardiovascular disease
<p>A huge amount of experimental and clinical evidences clearly demonstrate that the measurement of cardio-specific biomarkers [cardiac natriuretic peptides (CNP), and cardiac troponins (cTns)] can significantly and independently improve the diagnostic accuracy and risk stratification in cardiovascular diseases. Furthermore, several recent studies report that the measurement of cardio-specific biomarkers has a beneficial impact also on management and outcome of patients with cardiovascular diseases. Considering the significant and independent information associated to cardio-specific biomarkers, several studies have recently reported that the combined assay of CNP and cTns may be cost effective not only for diagnosis, prognosis and treatment of cardiac disease, but also for screening in general population of individuals at high cardiovascular risk. Due to the higher cost of their measurement in comparison to other laboratory tests, the clinical appropriateness of the combined measurement of CNP and cTns should be accurately evaluated. Accordingly, an increase in clinical utilization of a laboratory test should be based not only on the peculiar pathophysiological characteristics of a biomarker, but also on the high performance of immunoassay methods used for the biomarker measurement. From a pathophysiological point of view, elevated CNP values indicate that some stressor substances or situations are having an adverse impact on cardiac function; while an increase in cTn levels above the cut-off value indicates that a sustained or powerful stress has actually produced a damage on cardiomyocytes (i.e. a myocardial injury). Consequently , the combined measurement of CNP and cTns gives complementary and distinct rather than redundant clinical information. These two distinct pathophysiological mechanisms also explain why cardiovascular risk is strongly increased in patients with both CNP and cTns elevated. In conclusions, the combined measurement of CNP and cTns is a useful tool for diagnosis, follow-up, and stratification of risk in all patients with suspected cardiac disease, especially those admitted to the emergence department.</p>
Biochimica Clinica ; 44(2) S017-S031
Rassegne - Reviews
Le troponine I e T sono biomarcatori cardiaci interscambiabili?
Are troponin I and T interchangeable biomarkers?
<p>The most recent international guidelines recommend that high-sensitivity (hs) methods should be preferred for the measurement of cardiac troponin I (cTnI) and T (cTnT) for the detection of myocardial injury and the differential diagnosis of acute coronary syndromes. Furthermore, these guidelines state that there is no significant difference in accuracy among hs cTnI and cTnT methods for diagnosis of acute myocardial infarction. Myocardial injury is a prerequisite for the diagnosis of acute myocardial infarction, but it is also a distinct entity. The 2018 Fourth Universal Definition of Myocardial Infarction states that myocardial injury is detected when at least one value above the 99th percentile upper reference limit is measured in a patient by high-sensitivity methods for cTnI or cTnT. Occasionally, discrepancies between hs-cTnI and hs-cTnT test results can be found, when tested in the same blood sample. Several studies have reported discrepancies between hs-cTnI and hs-cTnT test results in some clinical conditions (especially chronic neuromuscular diseases) or even in apparently healthy subjects. This review, summarizes and discusses the biochemical, pathophysiological and analytical possible mechanisms causing discrepancies between hs-cTnI and hs-cTnT test results.</p>
Biochimica Clinica ; 44(2) S008-S016
Rassegne - Reviews
Metodo ad alta sensibilità per la misura della troponina I ed efficienza: risultati di un'esperienza
High-sensitive method to measure troponin I and efficiency: the results of an experience
AI. Leahu  |  MM. Mion  |  A. Padoan  |  M. Zaninotto  |  M. Plebani  | 
<p>Background: the development of improved methods for cardiac troponins measurement, characterized by higher analytical sensitivity, allows to adopt rapid rule-in and rule-out strategies by increasing diagnostic accuracy and optimizing the clinical and organizational pathways.<br />Methods: the efficiency achieved with the adoption of a high sensitive troponin I method, defined by its analytical characteristics a &ldquo;new generation&rdquo; method (STAT high sensitive troponin I, hs-TnI, Abbott Diagnostics), in place of a previous assay (LOCI CTNI, Siemens Health Care Diagnostics), has been evaluated. The results obtained in 1000 consecutive patients admitted to the Emergency Department (ED) with acute chest pain, in 2015 (before the new method) have been compared with those obtained in 1004 consecutive patients admitted in 2017 (after theintroduction of the hs-TnI method).<br />Results: in 2017 an increased number of troponin I baseline values higher than 99th percentile (10.7 versus8.3% in 2015, p = 0.089) has been observed. Furthermore, an improvement on the following clinical and organizational aspects has been detected in 2017: the adoption of an accelerated algorithm, being the median interval between two consecutive measurements 3 h and 18 min in 2017 and 4 h and 30 min in 2015 (p &lt;0.001); in the 75% of patients showing either positive or negative value at admission, the second measurement has been carried out within 180 min and 225 min (p = 0.024), respectively (in 2015 the timings were 239 e 337 min, p &lt;0.001, respectively). Finally, in 2017 a third troponin I measurement has been carried out in 0.4% of patients only (it was 3.5% in 2015, p = 0.044).<br />Conclusions: These data demonstrate a significant improvement in the patient management as well as an optimization of human and organizational resources with the adoption of a method with improved analytical performances to measure troponin I in ED.</p>
Biochimica Clinica ; 44(2) S054-S058
Contributi Scientifici - Scientific Papers
Troponina cardiaca ad alta sensibilità: risultati preliminari di un confronto tra un nuovo strumento “point-of-care” e i più comuni analizzatori impiegati nei laboratori clinici
High sensitivity cardiac troponin: preliminary results of a new point-of-care analyzer compared with the analyzers routinely used in clinical laboratories
<p>Introduction: cardiac troponin concentration measured using a point-of-care testing (POCT) analyzer could accelerate the management of patients awaiting assessment for suspected acute coronary syndrome without persistent ST-segment elevation in the emergency department (ED).<br />Methods: we evaluated a new high sensitivity cardiac troponin I (hs-cTnI) assay applied to the POCT PATHFAST&trade; (Gepa, Italia). The study of imprecision was carried out using commercial control materials and lithium-heparin plasma pools. The percentages of detectable hs-cTnI values between the Limit of Detection (LoD) and the 99th percentile as declared by the manufacturer were studied in a population of reference donors. The clinical diagnostic performance was evaluated in a population of patients presenting to the ED with chest pain (lithium-heparin plasma samples were collected at admission and 3 hours later), in comparison to the most common methods that measure hs-cTnI in clinical laboratories: Architect PLUS i2000SR, Dimension Vista, Advia Centaur XPT, UniCel DXI 800. Using the gender-specific 99thpercentile as declared from each manufacturer, the percentages of agreement and disagreement for the classification of hs-cTnI results were calculated as well as the Cohen&rsquo;s Kappa values.<br />Results: imprecision: concentration range (CV% range)=14.6-12227.3 ng/L (2.8-9.8%); % of hs-cTnI &gt;LoD and &lt;99th percentile in males and females were 30.0% and 18.5% respectively. The percentage ranges of agreement versus disagreement observed in the clinical study were 76.8-96.3% versus3.7-23.2% respectively, and the corresponding Cohen&rsquo;s Kappa values ranged from 0.532 to 0.864. The prevalence of discordant results was obtained on admission sample (range=59.1-83.3%).<br />Discussion: the observed analytical imprecision was satisfactory while the percentages of subjects with hs-cTnI&gt;LoD and &lt;99thpercentile were lower than those declared by the manufacturer because a limited number of subjects has been evaluated. The clinical performance has shown an overall satisfactory agreement with all the analytical platforms used.</p>
Biochimica Clinica ; 44(2) S059-S066
Contributi Scientifici - Scientific Papers
Valutazione del rischio cardiovascolare e del danno cardiaco asintomatico nella popolazione generale utilizzando la misura della troponina cardiaca con metodi ad alta sensibilità
Evaluation of cardiovascular risk and asymptomatic myocardial injury in the general population with high-sensitivity methods for cardiac troponin assay
<p>Only very recently the set-up of some immunoassay methods with high-sensitivity analytical performance allowed the accurate detection of cardiac troponin I (cTnI) and T (cTnT) levels in healthy adult subjects. Several studies have demonstrated the association between the risk of major cardiovascular events and cardiac troponin concentrations even for biomarker values within the reference intervals. High-sensitivity cTnI and cTnT methods enable to monitor myocardial renewal and remodelling, and to promptly identify patients at highest risk to heart failure development. An early and effective treatment of individuals at higher cardiovascular risk may revert the initial myocardial remodelling and slow down heart failure progression. Dedicated trials are needed also in Italian population to demonstrate the efficiency of general population screening by means of cost benefit analysis for individuals at higher risk for heart failure progression.</p>
Biochimica Clinica ; 44(2) S086-S096
Documenti SIBioC - SIBioC Documents
Determinazione della presepsina: non solo diagnosi di sepsi
Presepsin measurement: beyond sepsis diagnosis
G. Bragato  |  MM. Mion  |  A. Padoan  |  M. Zaninotto  |  M. Plebani  | 
<p>As sepsis is the leading cause of death among critically ill patients, early diagnosis is essential for the subsequent treatment to improve the outcome. Several diagnostic pathways have been proposed considering multiparametric approaches that combine clinical and biochemical evaluations. Among the several biomarkers proposed, procalcitonin measurement has been obtained significant consensus particularly in the evaluation of the efficacy of the therapeutic treatment. However, the need to define the prognosis and the outcome and to identify the patients at major risk of events during the hospitalization or at a short time later, seems to be an additional clinical value. The soluble cluster of differentiation 14 (S-CD14-ST or presepsin) is a free fragment of a glycoprotein expressed on monocytes and macrophages; several studies have demonstrated the significative prognostic value of the biomarker blood concentrations (at admission in particular) while the diagnostic performance of presepsin remains unclear. In a study carried out in a population of old patients (67-102 years) suffering from suspected pneumonia (n=50) the results of presepsin at admission in association with a Muldimensional Prognostic Index (MPI) score allow to identify the patients at major risk of adverse events (mortality) within 30 days. The prognostic efficiency of presepsin has been evaluated in different studies confirming, in different patient populations, the additional clinical value of this biomarker. Therefore, presepsin and prolacitonin measurements may provide complementary information that, in addition to clinical score and blood culture or molecular biology, can improve the management of patients with suspected sepsis.</p>
Biochimica Clinica ; 44(1) 068-072
Opinioni - Opinions
Interferenza da biotina negli immunodosaggi: raccomandazioni del Gruppo di Studio SIBioC sulla Variabilità Extra-Analitica (SIBioC-VEA)
Biotin interference in immunoassays: recommendations of the SIBioC Working Group on Extra-AnalyticalVariability (WG-VEA).
<p><span style="background-color:rgb(255, 255, 255); color:rgb(51, 51, 51); font-family:sans-serif,arial,verdana,trebuchet ms; font-size:13px">Biotin is a water-soluble vitamin, which participates to a vast array of metabolic pathwaysinvolving fatty acids, carbohydrates and amino acids metabolism. This vitamin is also capable to form high-affinitybonds with various molecules, including streptavidin and avidin, which are essential components of manyimmunoassays based on the principle of biotin-streptavidin or biotin-avidin binding. In patients assuming high dosesof biotin, therefore, some competitive and non-competitive immunoassays may exhibit falsely increased and falselydecreased test results, respectively, with magnitude of interference depending on biotin concentration in the testsample and on specific vulnerability of the immunoassay. With the aim to provide some expert guidance foridentifying, preventing and managing biotin interference in clinical laboratory practice, this document contains a seriesof consensus recommendations endorsed by the Working Group on Extra-Analytical Variability of the Italian Societyof Clinical Chemistry and Clinical Molecular Biology (SIBioC). Briefly, the most important recommendationsencompass local evaluation of possible biotin interference, routine history taking on biotin intake for both inpatientsand outpatients, informing clinicians on potentially biotin-sensitive immunoassays, sample retesting 24-48 hours afterthe last biotin administration, along with possible consideration to add a note in the laboratory report highlighting themethods more vulnerable to biotin interference. Routine biotin measurement in all samples is currently discouraged.</span></p>
Biochimica Clinica ; 43(3) 327-331
Garantire la comparabilità dei risultati nel rispetto dei requisiti di qualità e delle esigenze organizzative: l’esempio di una procedura operativa
How to guarantee the comparability of test results in compliance with the quality requirements andorganizational needs: the example of an operative procedure
<p>Medical laboratories are responsible for the qualityof test results, also when the same patient sample is evaluated using different analytical systems within the same lab.Indeed, as stated by ISO 15189:2012, laboratories should define means to compare procedures for evaluating thecomparability of patients&rsquo; samples results within the same healthcare system. In this study we report the approachused to define a procedure for assessing results comparability, developed in our laboratory before the ISO15189:2012 accreditation in 2016. Firstly, the approach was focused on the identification of all the different situationsthat may potentially require alignment of test results within the laboratory. Therefore, after evaluating guidelines anddocuments available in the literature, we defined a workflow applicable both to quantitative and qualitative methods.For quantitative methods, bias was estimated by means of statistical analyses such as Bland Altman and PassingBablok. For qualitative methods, results comparability was assessed by concordance. Criteria for defining theacceptability of systematic errors were also included in the procedure.</p>
Biochimica Clinica ; 43(2) 135-142
Contributi Scientifici - Scientific Papers
Protocollo operativo per la verifica della comparabilità dei risultati di laboratorio ottenuti su più procedure analitiche
Protocol to verify the comparability of quantitative laboratory results obtained with different measurementprocedures.
<p>With the growth and merging of clinical laboratories, very frequently analytical tests are performed onmultiple instruments within one or multiple locations. In these situations, there is the need of verifying thecomparability of patient results obtained with different analysers and/or different measurement procedures. Theimportance of this verification is further emphasised when considering that it is included into the ISO 15189specifications. This protocol provides step-by-step guidance on how to assess results comparability in differentscenarios. Up to four experimental designs are presented to meet laboratories&rsquo; needs, with details and examples onfrequency of testing, definition of acceptability criteria, samples selection, sample size calculation, statistical analysisand reporting.</p>
Biochimica Clinica ; 43(2) 228-243
Documenti SIBioC - SIBioC Documents
Gli indicatori di qualità nel processo di armonizzazione in Medicina di Laboratorio
Harmonization of quality indicators in Laboratory Medicine
<p>According to the International Standard for medical&nbsp;laboratories accreditation ISO 15189:2012, the laboratory should establish and periodically review quality indicators&nbsp;(QIs) to monitor and evaluate performance throughout critical aspects of pre-, intra and post-analytical processes.&nbsp;The use of QIs is needed to provide information and accountability to users and to establish a program of continuous&nbsp;improvement to ensure the quality of care and patient safety. In this context, we designed a QIs system as a part of&nbsp;a coherent and integrated quality improvement strategy. The management of QIs is based on an internal assessment&nbsp;system (IAS), which allows us to evaluate our performance over time and on the participation in an interlaboratory&nbsp;comparison managed as an EQA program, in order to compare our performance with other laboratories. The IAS&nbsp;includes a list of QIs, a form describing the specifications of each QI and a standard operating procedure. We&nbsp;participated in the project developed by the Working Group &ldquo;Laboratory errors and patient safety&rdquo; of IFCC on QIs.&nbsp;The project aims to identify a model of QIs that can be used worldwide through an EQA program. This paper aims to&nbsp;stimulate harmonization initiatives concerning QIs on the basis of the method and results of described experience.</p>
Biochimica Clinica ; 39(6) 601-608
Contributi scientifici - Scientific Papers
Identificazione di potenziali biomarcatori sierici di adenocarcinoma pancreatico
Identification of potential serum biomarkers of pancreatic cancer
A. Padoan  |  P. Fogar  |  E. Greco  |  E. Fadi  |  D. Bozzato  |  S. Moz  |  F. Navaglia  |  C.F. Zambon  |  R. Seraglia  |  M. Pelloso  |  A. Rossi  |  M. Plebani  | 
Biochimica Clinica ; 35(4) 280
Polimorfismi dei geni KLK3, RASA1 e NAALADL2: rischio di cancro alla prostata, aggressività della neoplasia e livelli sierici dell’Antigene Prostatico-Specifico
Polymorphisms of KLK3, RASA1 and NAALADL2 genes: prostate cancer risk, aggressiveness of neoplasia and serum PSA levels
D. Bozzato  |  C.F. Zambon  |  A. Padoan  |  M. Pelloso  |  A. Aita  |  S. Moz  |  F. Navaglia  |  T.P. Galetti  |  F. Zattoni  |  D. Basso  |  M. Plebani  | 
<p>Background: prostate cancer (Pca) is the second most common cancer among men and the sixth leading cause of death due to cancer among men worldwide. We aimed to verify if serum PSA levels and PCa risk/aggressiveness are modulated by polymorphisms of KLK3, RASA1 and NAALADL2 genes.<br />Methods: 1058 men have been studied; they consecutively underwent prostate biopsy for clinical suspicion of PCa. PCa was histologically diagnosed in 401 and ruled out in 657 men. Gleason score in PCa patients was &le;6 in 261, 7 in 83 and &gt;7 in the remaining 57 PCa. tPSA and f/tPSA levels were determined. Four polymorphisms were studied: rs35148638 (RASA1), rs78943174 (NAALADL2), rs2735839 and rs17632542 (KLK3).<br />Results: PCa diagnosis was significantly predicted by the KLK3 rs17632542 polymorphism (p&lt;0.001), tPSA (p&lt;0.001) and f/tPSA (p&lt;0.001). Carriers of the KLK3 rs17632542C rare allele had a significantly higher risk of PCa (p&lt;0.001) (OR 2.1, 95% CI 1.40-3.19). Gleason score &gt;7 was associated with increased tPSA (p&lt;0.001), decreased f/tPSA (p=0.003) and the KLK3 rs2735839 A rare allele (p= 0.004). In controls, tPSA was significantly lower in subjects bearing NAALADL2 rs78943174T rare allele (p=0.029). f/tPSA was higher in subjects with the KLK3 rs17632542C rare allele (p&lt;0.001) and with the RASA1 rs35148638 C/C genotypes (p=0.009). In PCa subjects, tPSA was not associated with the polymorphisms studied.<br />Conclusions: KLK3 rs17632542 and rs2735839 polymorphisms were significantly associated with the risk and aggressiveness of PCa respectively. NAALADL2, KLK3 rs17632542 and RASA1 polymorphisms were correlated with tPSA and f/tPSA serum levels, suggesting a genetically-based PSA expected values in absence of tumor. These results suggest a potential role of these polymorphisms as biomarkers for PCa in association with the diagnostic and prognostic indexes currently recognized.</p>
Biochimica Clinica ; 17(1)
Contributi Scientifici - Sscientific Papers