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Editor-in-chief
Maria Stella Graziani

Deputy Director
Martina Zaninotto

Associate Editors
Ferruccio Ceriotti
Davide Giavarina
Bruna Lo Sasso
Giampaolo Merlini
Martina Montagnana
Andrea Mosca
Paola Pezzati
Rossella Tomaiuolo
Matteo Vidali

EIC Assistant
Francesco Busardò

International Advisory Board Khosrow Adeli Canada
Sergio Bernardini Italy
Marcello Ciaccio Italy
Eleftherios Diamandis Canada
Philippe Gillery France
Kjell Grankvist Sweden
Hans Jacobs The Netherlands
Eric Kilpatrick UK
Magdalena Krintus Poland
Giuseppe Lippi Italy
Mario Plebani Italy
Sverre Sandberg Norway
Ana-Maria Simundic Croatia
Tommaso Trenti Italy
Cas Weykamp The Netherlands
Maria Willrich USA
Paul Yip Canada


Publisher
Biomedia srl
Via L. Temolo 4, 20126 Milano

Responsible Editor
Giuseppe Agosta

Editorial Secretary
Chiara Riva
Biomedia srl
Via L. Temolo 4, 20126 Milano
Tel. 0245498282
email: biochimica.clinica@sibioc.it

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ISSN print: 0393 – 0564
ISSN digital: 0392- 7091



BC: Articoli scritti da A. Padoan

Big Data e Intelligenza Artificiale in Medicina di Laboratorio
Artificial intelligence and big data in laboratory medicine
<p><span style="color:rgb(33, 29, 30); font-family:calibri,sans-serif; font-size:9pt">In the last few years, artificial intelligence (AI) is gaining attention in several medical disciplines, including laboratory medicine (LM). The raised interest on AI has been fueled not only by the huge amounts of information daily generated, but also by the special natural context offered by laboratories, where digitalization have already occupied an important part of the routine workflow of patients&rsquo; data. Motivated by these topics and under the auspices of SIBioC, a conference on AI and big data was organized in May 2022 in Bologna, Italy. This conference covered several topics of AI and big data, including but not limited to the current and future perspectives, comprising ethical challenges and the role of laboratory specialists, including young professionals, the productive integration of AI with information technologies and with other digital infrastructure, such as the LOINC and the block chain. Furthermore, some examples of real application of AI in LM were reported, including diagnosis and monitoring of familiar hypercholesterolemia, management of insulin treatments for diabetes, reference intervals identification and verification by indirect methods, COVID-19 diagnosis and the monitoring of outpatients monoclonal gammopathy treatment by digital healthcare</span></p>
Biochimica Clinica ; 47(1) 074-081
Documenti - Documents
 
Big data e intelligenza artificiale in medicina di laboratorio: una indagine SiBioC nei i laboratori clinici italiani
A survey on Artificial Intelligence and Big Data utilisation in Italian Clinical Laboratories
<p>Objectives: the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) Big Data and Artificial Intelligence (BAI) Working Group promoted a survey to frame the knowledge, skills, and technological predisposition in Clinical Laboratories. Methods: questionnaire, focusing on digitization, IT infrastructures, data accessibility, and BAI projects underway was sent to 1351 SIBioC participants. The responses were evaluated using SurveyMonkey software and Google Sheets. Results: the 227 respondents (17%) from all over Italy (47% of 484 labs), mainly biologists, laboratory physicians and managers, mostly from laboratories of public hospitals, revealed lack of hardware, software and corporate Wi-Fi, and dearth of PCs. Only 25% work daily on clouds, while 65%-including Laboratory Directors-cannot acquire health data from sources other than laboratories. Only 50% of those with access can review a clinical patient&rsquo;s health record, while the other access only to laboratory information. The integration of laboratory data with other health data is mostly incomplete, which limits BAI-type analysis. Many are unaware of integration platforms. Over 90% report pulling data from the LIS, with varying degrees of autonomy. Very few have already undertaken BAI projects, frequently relying on IT partnerships. The majority consider BAI as crucial in helping professional judgments, indicating a growing interest. Conclusions: the questionnaire received relevant feedback from SIBioC participants. It highlighted the level of expertise and interest in BAI applications. None of the obstacles stands out more than the others, emphasising the need to allaround work: IT infrastructures, data warehouses, BAI analysis software acquisition, data accessibility and training.</p>
Biochimica Clinica ; 47(1) 056-064
Contributi Scientifici - Scientific Papers
 
Determinazione di anticorpi anti SARS-CoV-2 in matrice salivare in individui vaccinati e in pazienti COVID-19
Determination of anti-sars-cov-2 antibodies in salivary samples from vaccinated individuals and COVID-19 patients.
<p>Introduction: Saliva is a promising biological fluid to be used for measuring a number of analytes. Aim of this ppaperis to verify if salivary anti-SARS-CoV-2 antibodies determination could be suitable for monitoring the viral spread andvaccination efficacy during the COVID-19 epidemic.Methods: a total of 69 subjects were enrolled at the Padova University Hospital: 39 COVID-19 patients and 30 health careworkers (HCW), who underwent a complete vaccination cycle with BNT162b2. All subjects collected a salivary sample,using Salivette, (SARSTEDT AG &amp; Co, N&uuml;mbrecht, Germany). For 9 HCW, salivary samples were collected at threedifferent times within the same day. A serum sample was also obtained for all individuals. Salivary COVID-19 N/S1 RBD(sal-IgG) and serum anti-SARS-CoV-2 S-RBD IgG Ab (ser-IgG) were used for determining anti SARS-CoV-2 antibodies.Results: positive sal-IgG were found in 67/69 (97.1%) samples; in serum samples, the positivity for ser-IgG was foundin 68/69 (98.6%). The sal-IgG median levels differed from COVID-19 to vaccinated HCW, being 0,21 kAU/L in patientssamples and 0,8 kAU/L in vaccinated HCV samples (p =0.030). Median levels for ser-IgG in COVID-19 and patientsvaccinated HCW were 121 kBAU/L and 940 kBAU/L (p &lt;0.001) respectively. A statistically significant correlation was foundbetween ser-IgG levels and time post-vaccination in HCW (rho =-0.6292, p &lt;0.001). Sal-IgG levels were not influencedby the daytime of collection (rho =0.148, p=0.373). Passing-Bablok regressions showed that sal-IgG and ser-IgGcomparability was assessable only when ser-IgG values were divided by 1000, showing slope and intercept values of 0.016(95%CI: 0.016-0.078) and 0,221 (95%CI:-0.097 to 0.786), respectively.Conclusions: sal-IgG are detectable both in COVID-19 and in vaccinated individuals and the values are not influencedby the daytime of collection. As expected sal-IgG were much lower than ser-IgG.</p>
Biochimica Clinica ; 47(1) 041-045
Contributi Scientifici - Scientific Paper
 
Evaluation of the cardiovascular risk in patients undergoing major non-cardiac surgery: role of cardiac-specific biomarkers
Evaluation of the cardiovascular risk in patients undergoing major non-cardiac surgery: role of cardiac-specific biomarkers
<p>Cardiovascular risk evaluation in patients undergoing major non-cardiac surgery: role of cardiac-specific biomarkers.</p><p>Joint document of the Italian Societies of Clinical Biochemistry: European Ligand Assay Society, Sezione Italiana (ELAS), Societ&agrave; Italiana di Biochimica Clinica e Biologia Molecolare Clinica (SIBioC), Societ&agrave; Italiana di Patologia Clinica e Medicina di Laboratorio (SIPMeL) Patients undergoing major surgery have a substantial risk of cardiovascular events during the perioperative period.</p><p>Despite the introduction of several risk scores based on medical history, classical risk factors and non-invasive cardiac tests, the possibility to predict cardiovascular events in patients undergoing non-cardiac surgery remains limited. The cardiac-specific biomarkers natriuretic peptides (NPs) and cardiac troponins (cTn) have been proposed as additional tools for risk prediction in the peri-operative period. This Consensus Document aims to discuss the value of preoperative levels and perioperative changes in cardiac-specific biomarkers to predict adverse outcomes in patients undergoing major non-cardiac surgery. Based on several prospective observational studies and 6 meta-analyses, some guidelines recommended the measurement of NPs to refine perioperative cardiac risk estimation in patients undergoing noncardiac surgery. More recently, several studies reported a higher mortality in surgical patients presenting an elevation in high-sensitivity cTnT and cTnI, especially in elderly patients or those with comorbidities. This evidence should be considered in future international guidelines on the evaluation of perioperative risk in patients undergoing major noncardiac surgery.</p>
Biochimica Clinica ; 46(3) 255-267
Documenti SIBioC - SIBioC Documents
 
Il ruolo del laboratorio nel monitoraggio della gravidanza fisiologica
Laboratory tests to monitoring physiological pregnancy.
A. Padoan  |  S. Visentin  | 
<p><span style="font-family:calibri,sans-serif; font-size:12px">A series of profound physiological changes happen during pregnancy in women body, mainly to facilitate the proper growth and development of the embryo and fetus. These changes include any organ and system in the body, causing hormonal and metabolic modifications and plasma volume increase. In the clinical laboratory the measurement of several biological constituents simultaneously is possible and, hence, laboratory tests play an essential role in monitoring physiological pregnancy as well as in detecting pathological alterations when present. Further, the assessment of laboratory parameters during pregnancy is considered as part of the routine examination for pregnant women, and it is included in National and International antenatal care programs. For this purpose, antenatal screening programs usually include complete blood count, blood group and antibody screen as well as urine evaluation and measurement of glycemic conditions. Syphilis, HIV and Hepatitis are also usually evaluated to prevent transmission to the newborn. Appropriate pregnancy reference intervals are also needed to help clinicians to interpret correctly laboratory results in pregnant women</span></p>
Biochimica Clinica ; 46(3) S011-S018
Rassegne - Reviews
 
Diagnostica molecolare per il SARS-CoV-2: un programma sperimentale per la Valutazione Esterna di Qualità del Centro di Ricerca Biomedica per la Qualità in Medicina di Laboratorio
Molecular diagnostic for SARS-CoV-2: an experimental External Quality Assessment Scheme
<p>Introduction: External Quality Assessment (EQA) is a valuable tool to monitor and improve the analytical performances of clinical laboratories. To guarantee suitable results also during the COVID-19 pandemic, EQA scheme providers have implemented specific schemes assessing different SARS-CoV-2 diagnostic systems. This study aims to describe the results collected in an experimental EQA scheme for molecular diagnostic of SARS-CoV-2 managed by INSTAND e.V. with the collaboration of the Centre of Biomedical Research for Quality in Laboratory Medicine for Veneto Region Laboratories. Methods: the qualitative EQA results collected in three surveys (two in 2020 and one in 2021) for 18 samples total, have been summarized to identify the percentage of laboratory results per sample. Control samples were provided by NationalesKonsiliarlaboratorium fur Coronaviren of Berlin. Results: even though the average of the participating laboratories strongly decreased between surveys, a good agreement was found among results (95% to 99.8%). A totally of 0.2% - 4% of incorrect results and 0% - 1.1% of indeterminate results were reported. In addition, the sequencing analysis and the point mutations analysis, included in the last analyzed survey, revealed a good agreement between participating laboratories with an overall score from 74.8% to 89.6% for the sequencing and from 90.65% to 95.33% for the point mutations, respectively. Conclusions: the EQA programs are a fundamental quality assurance tool to evaluate the laboratory performance and to appreciate the State-of-the-Art of the different diagnostic systems used by participating laboratories. The need for an EQA scheme for every test performed in the laboratory is mandatory to guarantee patient safety.</p>
Biochimica Clinica ; 46(2) 126-133
Contributi Scientifici - Scientific Papers
 
Errori di identificazione del paziente: un progetto SIBioC orientato alla gestione di un problema persistente
Wrong blood in tube: a SIBioC project for a persistent problem
A. Aita  |  A. Padoan  |  R. Guerranti  |  M. Fiorini  |  C. Bellini  |  F. Tosato  |  M. Pelloso  |  E. Piva  |  R. Pajola  |  M. Lorubbio  |  B. Cremonesi  |  A. Bassi  |  R. Rolla  |  G. Introcaso  |  M. Plebani  |  S. Buoro  |  F. Balboni  | 
<p>Introduction: recently, multi-analytes delta-check (MDC) has been proposed as a more effective tool in identification errors (IE) prevention. In this context, &ldquo;Haematology&rdquo; and &ldquo;Clinical Risk&rdquo; SIBioC working groups launched a project aiming to develop a cell blood count (CBC) MDC. This work is aimed to describe the project and some preliminary results.<br />Methods: the project consists of four phases: collection of CBC results from 15 Italian laboratories to create an original dataset (OD); pilot study on a smaller dataset (SD) i.e., creation of an artificial mix-up dataset-MD containing IE by casual resampling of the SD and identification of the best statistical model to create a MDC; identification of the most accurate MDC on OD; testing the MDC in involved labs and verification of its effectiveness.<br />Results: the SD included 2,367 pair of consecutive results for the same patient (patients&rsquo; age: 0-100 years; the majority of repetitions were within days). The SD casual resampling generated a MD with 2,000 pair of patient-mixed consecutive results. When one of the most frequent used delta-check alert (&Delta;MCV=7fL) was applied to detect IE in MD, the method accuracy was low (AUC=0.542). On the contrary, testing of a multivariate model, obtained by a stepwise logistic analysis, allowed to obtain a more accurate MDC in IE detection (AUC=0.931, sensitivity=91.6%, specificity=94%).<br />Conclusions: MDC may offer a practical strategy to identify IE prior to test reporting, improving patient safety. However a good planning of project workflow, selection of methodology, tools and staff competence are key elements to reach the objectives.</p>
Biochimica Clinica ; 46(1) 051-057
Contributi Scientifici - Scientific Papers
 
Utilizzo in Pronto Soccorso dei metodi ad alta sensibilità per le troponine cardiache per i pazienti con sospetto di infarto acuto del miocardio senza sopraslivellamente del tratto ST Documento Congiunto del Gruppo di Studio Inter-Societario sui Biomarcatori Cardiaci delle Società Italiane di Biochimica Clinica: European Ligand Assay Society, Sezione Italiana (ELAS), Società Italiana di Biochimica Clinica e Biologia Molecolare Clinica (SIBioC), Società Italiana di Patalogia Clinica e Medicina di Laboratorio
Use of the high-sensitivity methods for cardiac troponins measurement in patients admitted to the Emergency Department with a clinical suspicion of a non-ST segment elevation myocardial infarction Joint document of the Italian Societies of Clinical Biochemistry: European Ligand Assay Society, Sezione Italiana (ELAS), Società Italiana di Biochimica Clinica e Biologia Molecolare Clinica (SIBioC), Società Italiana di Patologia Clinica e Medicina di Laboratorio (SIPMeL).
<p>The use of serial measurement of cardiac troponin (cTn) is recommended by international guidelines for the diagnosis of myocardial infarction (MI) since 2000. However, the are some relevant differences among the recommendations proposed by the three different international guidelines published in 2020-2021 for the management of patients admitted to the Emergency Department (ED) with a clinical suspicion of a non-ST-segment elevation MI (NSTEMI). In particular, there is no agreement among these authoritative international guidelines about the cut-off or absolute change values to be used for diagnosis of MI. Another important controversial issue is whether there are, at present time, sufficient evidences on the diagnostic accuracy and cost effectiveness related to cut-off values suggested for the most rapid algorithms (0-1 or 0-2 hours) recommended for the rule-in/rule-out of NSTEMI. Finally, another important issue concerns the possible bias existing between the demographic and clinical characteritics of the patients enrolled in some multicenter trials compared to those routinely admitted to ED of the city Hospitals of some European countries, including Italy, for the diagnosis of NSTEMI. Considering the recommendations from these international guidelines, the Study Group of Cardiac Biomarkers, supported by the Italian Scientific Societies SIBioC&nbsp;(Societ&agrave; Italiana di Biochimica Clinica), ELAS (Italian Society of the European Ligand Assay Society) and SIPMeL (Societ&agrave; Italiana di Patologia Clinica e medicina di Laboraratorio), decided to revise the document previously published in 2013 about the management of patients admitted to ED with suspect NSTEMI, and so to prepare suggestions more specifically designed for the clinical institutions operating in the healthcare system in Italy.</p>
Biochimica Clinica ; 45(4) 412-426
Documenti SIBioC - SIBioC Documents
 
Approcci diagnostici innovativi per le malattie infiammatorie croniche intestinali
New diagnostic approaches for inflammatory bowel diseases
<p>Inflammatory bowel diseases (IBD), that include ulcerative colitis (UC) and Crohn&rsquo;s disease (CD) are among the most serious and perplexing digestive diseases. Indeed, diagnosis is sometimes delayed due to the variability and subtlety of its initial manifestations, especially in CD. Since no gold standard is currently defined for the diagnosis and monitoring of IBD, a number of genomic, metabolomic and proteomic studies have tried to address this issue. After illustrating the traditional diagnostic approach (mainly fecal calprotectin), this Opinion Paper reports about the utility of some new biomarkers (micro-RNA, proteomic and metabolomic markers). In particular, the results of a study on fecal peptides are commented. After verifying that proteolytic degradation was clearly visible in fecal samples of a number of control (n=34) and patients with IBD (n=133), the matrix-assisted laser desorption ionization (MALDI) time of flight (TOF) mass spectrometry was used to evaluate peptides patterns of fecal samples, in a range from 1000 to 4000 Da. This cohort was used to derive an algorithm for IBD diagnosis. Diagnostic performances were then estimated using an additional validation cohort, including subjects with IBD (n=42) and without IBD (n= 28). Sensitivity was 54.8% (95%CI: 38.7%&ndash;70.2%) and specificity 96.4% (95%CI: 81.7%&ndash;99.9%) with a positive and a negative predictive value of 95.8% (95%CI: 76.7%&ndash;99.4%) and 58.7% (95%CI: 50.3&ndash;66.6%), respectively. In comparison, fecal calprotectin, achieved sensitivity and specificity of 78.6% (95%CI: 63.2%&ndash;89.7%) and 42.9% (95%CI: 24.5%&ndash;62.8%). In spite of the obtained good diagnostic performances, any candidate biomarker, once identified, should be carefully validated before being translated into clinical practice.</p>
Biochimica Clinica ; 45(1) 052-056
Opinioni - Opinions
 
Biomarcatori cardiaci: dove stiamo andando?
Cardiac biomarkers: where are we going?
<p>The measurement of cardiac troponins (cTn) is recommended by all guidelines as the gold standard for the detection of differential myocardial injury and acute myocardial infarction (AMI). In this article, some key issues regarding both analytical characteristics of the high-sensitivity methods for cTn, which are still considered controversial or unresolved are discussed in details. These issues have been included in the activities of the Joint Working Group on &ldquo;Cardiac Biomarkers&rdquo; of the Italian Society of Clinical Biochemistry and the Italian branch of the European Ligand Assay Society. The major clinical concern regarding hs-cTn methods is the difficulty to differentiate the pathophysiological mechanism responsible for biomarker release from cardiomyocytes after reversible or irreversible injury, respectively. High-sensitivity cTnI and cTnT methods (hs-cTn) enable to monitor myocardial renewal and remodelling, and to promptly identify patients at highest risk of heart failure. In addition, several studies demonstrated that the cardiovascular risk progressively increases in the general population even for hs-cTn values well below the 99th percentile, i.e. the recognized cut-off for the detection of myocardial injury and diagnosis of AMI. An early and effective treatment of individuals at higher cardiovascular risk may revert the initial myocardial remodelling and slow down heart failure progression. Finally, recent studies support the working hypothesis that a new generation of hs-cTn methods should be set up based on monoclonal antibodies, specific for circulating peptide forms more characteristics for reversible rather than irreversible myocardial injury. Of course, screening programs of cardiovascular risk stratification and prevention strategies using hs-cTn methods require further investigation to define the optimal target populations, timing of measurement, and preventive interventions.</p>
Biochimica Clinica ; 45(1) 068-074
Documenti - Documents
 
Introduzione ai Big Data e all’Intelligenza Artificiale in Medicina di Laboratorio
Introduction to Big Data and Artificial Intelligence in Laboratory Medicine
<p>Currently, thanks to the growing computing capacity and the increasing availability of digital data, Data Science is playing an important role in the future development of Laboratory Medicine. However, the concepts of Big Data (BD) and Artificial Intelligence (AI) can still be interpreted in various ways. Clinical laboratories are certainly among the health care organizations producing an important number of data that can be considered BD and it is certainly not a coincidence that they are among the first health organizations to have implemented computer systems within their workflows. Through a process called Data Mining it is possible to extract useful information from BD using automatic or semi-automatic methods that must be preceded by Data Cleaning in order to ensure the cleanliness and correctness of the data themself. Regarding Data Analysis, several Machine Learning or Deep Learning techniques based on different algorithms or on the functioning principle of neural networks can be used; for the development of these techniques, R and Python programming languages are really useful. Although many applications can be useful in Laboratory Medicine, there are still some obstacles to overcome, including poor harmonization of data or fragmentation of sources; moreover, the issue of data accessibility must be managed considering patient&rsquo;s privacy as a priority. Finally, there is an increase apprehension related to the awareness of the inevitable innovation in the Laboratory Medicine field in the near future, because of these new approaches. To face these challenges, it is necessary that these topics become familiar to the professionals of Laboratory Medicine. Aim of this Document is to share information about BD and AI in order to contribute to the introduction and development of these methodologies in the field of Laboratory Medicine.</p>
Biochimica Clinica ; 45(1) 057-067
Documenti - Documents
 
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 ; 44(4) 359-366
Contributi Scientifici - Sscientific Papers
 
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
Documenti SIBioC - SIBioC DOCUMENTS
 
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
 
Armonizzazione in Medicina di Laboratorio
Harmonization in Laboratory Medicine
F. Ceriotti  |  M. Panteghini  |  A. Tosetto  |  V. Valentini  |  L. Politi  |  R. Rolla  |  T. Guastafierro  |  T. Köken  |  E. Capoluongo  |  C. Mazzaccara  |  V. D'Argenio  |  V. D'Argenio  |  G. Lippi  |  M. Plebani  |  D. Giavarina  |  M. Berardi  |   A survey on sample matrix and preanalytical management in clinical laboratories  |  D. Bozzato  |  G. Messeri  |  M. Zaninotto  |  M. Vidali  |  A. Padoan  |  G. Parigi  |  A. Clerico  |  L. Sciacovelli  |  M. Ciaccio  |  G.L. Salvagno  |  G. Barberio  |  G. Barberio  |  G.L. Salvagno  |  M. Pepe  |  M. Panteghini  |  F. Braga  |  G. Gessoni  |  M. Montagnana  |  N. Doğan  |  M. Barberis  |  M. Barberis  |  A. Marchetti  |  F. Borrillo  |  L. Bonfanti  |  P.M. Ness  |  G. Messeri  |  S. Nannini  |  J. Queraltò  |  M. Zaninotto  |  A. Mosca  |  BM. Henry  |  G. Santini  |  A. Coglianese  |  V. D'Argenio  |  E. Fiorio  |  L. Crinò  |  M. A. V. Willrich  |  A. Modenese  |  M. Berardi  |  G. Nordera  |  M. Girelli  |  R. Tomaiuolo  |  D. Giavarina  |  R. Dittadi  |  L. Pighi  |  V. Guaraldo  |  G. Bambagiotti  |  E. Franceschini  |  R. Danesi  |  M. Locatelli  |  F. Balboni  |  D. Cosseddu  |  M. Savoia  |  S. Bernardini  |  C. Domenichini  |  M. Lamonaca  |  M. Perrone  |  M. Perrone  |   per il Gruppo di Studio Intersocietario SIBioC-SIPMeL Diabete Mellito  |  P. Pradella  |  A. Padoan  |  M.T. Sandri  |  L. Belloni  |  A. D'Avolio  |  T. Trenti  |  A. Fortunato  |  T. Trenti  | 
Biochimica Clinica ; 39(6) 546-547
Editoriale - Editorial
 
Armonizzazione in Medicina di Laboratorio
Harmonization in Laboratory Medicine
F. Ceriotti  |  M. Panteghini  |  A. Tosetto  |  V. Valentini  |  L. Politi  |  R. Rolla  |  T. Guastafierro  |  T. Köken  |  E. Capoluongo  |  C. Mazzaccara  |  V. D'Argenio  |  V. D'Argenio  |  G. Lippi  |  M. Plebani  |  D. Giavarina  |  M. Berardi  |   A survey on sample matrix and preanalytical management in clinical laboratories  |  D. Bozzato  |  G. Messeri  |  M. Zaninotto  |  M. Vidali  |  A. Padoan  |  G. Parigi  |  A. Clerico  |  L. Sciacovelli  |  M. Ciaccio  |  G.L. Salvagno  |  G. Barberio  |  G. Barberio  |  G.L. Salvagno  |  M. Pepe  |  M. Panteghini  |  F. Braga  |  G. Gessoni  |  M. Montagnana  |  N. Doğan  |  M. Barberis  |  M. Barberis  |  A. Marchetti  |  F. Borrillo  |  L. Bonfanti  |  P.M. Ness  |  G. Messeri  |  S. Nannini  |  J. Queraltò  |  M. Zaninotto  |  A. Mosca  |  BM. Henry  |  G. Santini  |  A. Coglianese  |  V. D'Argenio  |  E. Fiorio  |  L. Crinò  |  M. A. V. Willrich  |  A. Modenese  |  M. Berardi  |  G. Nordera  |  M. Girelli  |  R. Tomaiuolo  |  D. Giavarina  |  R. Dittadi  |  L. Pighi  |  V. Guaraldo  |  G. Bambagiotti  |  E. Franceschini  |  R. Danesi  |  M. Locatelli  |  F. Balboni  |  D. Cosseddu  |  M. Savoia  |  S. Bernardini  |  C. Domenichini  |  M. Lamonaca  |  M. Perrone  |  M. Perrone  |   per il Gruppo di Studio Intersocietario SIBioC-SIPMeL Diabete Mellito  |  P. Pradella  |  A. Padoan  |  M.T. Sandri  |  L. Belloni  |  A. D'Avolio  |  T. Trenti  |  A. Fortunato  |  T. Trenti  | 
Biochimica Clinica ; 39(6) 546-547
Editoriale - Editorial
 
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
CONTRIBUTI SCIENTIFICI - CONTRIBUTI SCIENTIFICI