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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

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


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

BC: Articoli scritti da F. Ceriotti

Colesterolo HDL: mortalità e rischio cardiovascolare
Biochimica Clinica ; 47(1) 010-011
Editoriale - Editorial
Saliva: Challenges, possibilities, and limits of the diagnostic use Part 2 – Pre-analytical and analytical aspects
<p><span style="font-size:12px">Part I of this review was dedicated to the biological complexity of saliva and its relationship with the pathophysiology of many organs. In Part II, issues related to the pre-analytical and analytical phases are illustrated, focusing first the attention on the main sources of variability, starting from the few data available on biological variation to the different approaches for sample collection under basal or stimulated conditions. Up to now, published data, obtained on small groups of healthy or diseased individuals, seem to be indicative of wide pre-analytical errors and/or individual variability. The established clinical use of salivary tests is then reviewed and a series of possible new applications are presented. Methodologies employed in saliva are presented, ranging from commonly applied techniques, such as colorimetric enzymatic methods and ELISA, to more sophisticated technologies (gas chromatography&ndash;mass spectrometry, liquid chromatography-mass spectrometry and 1H NMR spectroscopy) to investigate proteomics and metabolomics. The aim of this review is to present the pre-analytical issues related to its collection and storage and to illustrate the knowledge gaps and the numerous opportunities that the analysis of this interesting biological fluid may offer.</span></p>
Biochimica Clinica ; 47(1) 012-028
Rassegne - Reviews
Saliva: challenges, possibilities, and limits of the diagnostic use Part 1 - Anatomical and basic pathophysiological aspects
Saliva: challenges, possibilities, and limits of the diagnostic use Part 1 - Anatomical and basic pathophysiological aspects
<p><span style="color:rgb(34, 30, 31); font-size:9pt">This review presents a detailed description of the saliva physiology (sources, composition, regulation of secretion) illustrating the complexity of this body fluid and its relationship with the pathophysiology of many organs. The knowledge of these aspects are of paramount importance to deeply understand main sources of variability, in keeping under control the pre-analytical phase and also to try to explain some contradictory results found in literature.&nbsp;</span><span style="color:rgb(34, 30, 31); font-size:9pt">Saliva is a biofluid with very interesting advantages: it is easy to self-collect, transport, and store. It is expected that saliva will have a key future role in the diagnosis of many diseases (metabolic disorders, cancer, oral and dental diseases, etc.) and useful for point-of-care testing.&nbsp;</span><span style="color:rgb(34, 30, 31); font-size:9pt">Part I of this review is a basic introduction to the saliva biological complexity; part II will follow, dealing with issues related to the pre-analytical and analytical phase.</span></p>
Biochimica Clinica ; 46(4) 292-300
Rassegne - Reviews
Sviluppo e validazione di un metodo analitico per la misurazione in neonati dell'ormone della crescita in campioni eluiti da carte filtro
Development and validation of a method for the measurement of growth hormone in newborns on dried blood spots.
<p>Introduction: severe deficiency of Growth Hormone (GHD) of the newborn is a rare but potentially life-threatening disease. GH can be measured during the first week of life when levels are physiologically higher. Aim of the study was to validate a method to measure GH in newborns from dried blood spots (DBS) for reference interval estimation. Methods: whole EDTA-blood and serum were&nbsp; collected from patients attending the Endocrinology Unit. 50 &micro;L of EDTA-blood was spotted onto Guthrie cards (LTA Srl) which were air dried at room temperature (RT) for 4 hours and processed or stored at -20&deg;C up to 8 months. Three disks (5.5 mm) were punched out into a 2 mL polypropylene tube and 250 &micro;L of PBS1x were added. Samples were incubated at RT for 16 hours and then centrifuged at 12 500 rpm for 1 min. GH in supernatants or undiluted sera was determined by Immulite 2000 (Siemens Healthineers) and a calibration curve was built. Results: linearity was verified (R2 &gt;0.99) up to 50 &micro;g/L. At 1 &micro;g/L, considered the Limit of Quantification (LOQ), CV% resulted to be 11%. Repeatability at 8 concentrations (from 1.5 to 50 &micro;g/L) ranged from 2.4% to 11.1%. At 7 &micro;g/L, the cut-off previously reported by literature for GHD, CV% was 3.7%. Within-laboratory imprecision, evaluated in a period of 8 months at two different concentrations (3.4 &micro;g/L and 10.1 &micro;g/L) was 13% and 5.9%, respectively. Conclusions. The new method displayed good analytical performances, suggesting it can be used to measure GH in newborns using DBS for reference interval estimation.</p>
Biochimica Clinica ; 46(4) 325
Contributi Scientifici - Scientific Papers
Preziose informazioni dall’esame del liquido pericardico
Valuable information from the examination of the pericardial fluid
<p><span style="font-family:calibri,sans-serif; font-size:9.0pt">A 63-year-old man, without previously known cancer disease, arrived at the Emergency room because of severe dyspnea. Electrocardiogram revealed right branch block and low ventricular repolarization voltages. Chest X ray and echocardiogram, instead, showed right pleural effusion and cardiac massive effusion. The patient underwent pericardiocentesis. The morphological study of pericardial fluid revealed the presence of numerous nonhematopoietic cells and the patient was admitted to the hosptital Thoracentesis was performed during hospitalization. The analysis of pleural fluid showed similar results to those obtained in pericardial fluid. A subsequent paracentesis was performed. Accordingly, this fluid showed similar atypical cells. Adenopathy in the supraclavicular area was found at the TC scan. Lymphnode biopsy confirmed a poorly differentiated proliferation, consistent with squamous cell carcinoma. In conclusion, morphological analysis of the pericardial fluid is a simple examination that, in a short time, may alert about the presence of unexpected atypical cells.</span></p>
Biochimica Clinica ; 46(3) e18-e21
Casi Clinici - Case Report
Performance evaluation of ARKRAY HA-8190V system for measuring glycated hemoglobin
Performance evaluation of ARKRAY HA-8190V system for measuring glycated hemoglobin
R. Paleari  |  F. Ceriotti  |  A. Mosca  | 
<p>Introduction: the new fully automated HPLC ion-exchange system ADAMS A1c HA-8190V analyzer, developed by ARKRAY Inc., running in two different modes (Variant and Fast) has been evaluated.<br />Methods: reproducibility was evaluated according to the EP-15A3 standard. Method comparison was performed on 122 fresh blood samples, according to the EP-9 standard. The system was compared to 3 other HPLC analyzers, based on ion-exchange (Tosoh G11 and Bio-Rad D-100) and boronate affinity chromatography (Trinity Biotech Premier Hb9210). Usability was evaluated by using to a score evaluation system.<br />Results: reproducibility proved to be very good at normal and high HbA1c concentration, with total CVs always &lt;0.7 %, when HbA1c was expressed in mmol/mol as well as in % units. The HA-8190V system was well correlated to the other HPLC analyzers, with a mean bias not clinically relevant. Finally, the usability of the system was evaluated and proved to be well acceptable.<br />Conclusions: the ARKRAY HA-8190 V system was found to be a reliable and suitable method for routine HbA1c measurement in clinical chemistry laboratories.</p>
Biochimica Clinica ; 46(1) 068-073
Contributi Scientifici - Scientific Papers
Il laboratorio clinico al tempo del COVID-19
F. Ceriotti  | 
Biochimica Clinica ; 45(4) 335
Editoriale - Editorial
Antibody identification in COVID-19 pandemic: a comparison between immunochemiluminescence and immunochromatography methods
<p>Introduction: in the fight against the COVID-19 pandemic, the determination of the serum antibodies against SARS-CoV-2 is highly relevant, although the reliability of the results delivered is sometimes questionable. The aim of this paper is to evaluate the performances of a rapid immunochromatography test for IgG and IgM antibodies, comparing them with an immunochemiluminescence method.<br />Methods: we analyzed 357 sera for the presence of IgG anti-SARS-CoV-2 spike proteins S1/S2 with an automated immunochemiluminescent test (DiaSorin&reg;) and the presence of IgG and IgM anti-SARS-CoV-2 nucleocapside protein with an immunochromatography method (LEPU&reg;) based on lateral flow technology.<br />Results: with Diasorin&reg; method, 248 subjects resulted to be negative and 109 positives, whereas LEPU&reg; test was positive (IgM+ and/or IgG+) in 98 subjects. The overall concordance between LEPU&reg; and DiaSorin&reg;, was 94.1% (95% CI 91.0-96.2). Cohen&rsquo;s kappa was 0.86 (95% CI 0.80-0.92), indicating good agreement. 21 out of 357 (5.9%) samples had a discordant result and were re-analyzed with a third method (Roche Diagnostics Electrochemiluminescence&reg;): 4 out of 5 DiaSorin&reg; negative/LEPU&reg; positive samples were confirmed as negative by Roche&reg;; conversely, among the 16 DiaSorin&reg; positive/LEPU&reg; negative samples, 5 were confirmed as positive by Roche&reg;, 6 as negative and 5 were not retested due to insufficient sample volume.<br />Conclusions: despite the methods were designed to detect different antibodies an overall high agreement between techniques was found. Discrepant results were found and were likely due to different antigen targets recognized by methods. The observation that only 6 out of 11 DiaSorin&reg; positive samples were not confirmed by ROCHE&reg;, supports the antigen-dependent hypothesis.</p>
Biochimica Clinica ; 45(2) 153-157
Contributi Scientifici - Scientific Papers
Valutazione di IgG e IgM anti-SARS-CoV-2 su Maglumi 800 (Snibe)
Evaluation of Anti-SARS-CoV-2 immunoglobulin G and M on Snibe Maglumi 800
<p>Introduction: the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a due to new beta-coronavirus causing the pandemic called Coronavirus disease 2019 (COVID-19). The evaluation of the presence of immunoglobulin G and M anti-SARS-CoV-2 (IgG and IgM) is important to understand the epidemiology of the disease and to confirm the presence of the disease when clinical signs are present, but RNA is not detected.<br />Methods: leftover serum samples from different types of patients were used: sera from biobank collected in 2018 as negative controls; patients recovering from the disease as positive controls; patients presenting at the Emergency Room with a positive rhino-pharyngeal swab; patients in Intensive Care Units. Anti-SARS-CoV-2 IgG and IgM were measured with MAGLUMI 2019-nCoV IgM/IgG Kits on Maglumi 800.<br />Results: one out of 61 expected negative resulted positive, and 2 were borderline for IgG (95% specificity, 95%CI 89.6-100), 1 positive for IgM (98.4% specificity, 95%CI 95.2-100); one out of 41 expected IgG positive resulted negative (97.6% sensitivity, 95%CI 92.8-100). All the 13 Intensive Care patients were positive for IgG, 11 for IgM. IgG were negative in 50.9% of the 55 swab positive from Emergency Room patients, while IgM were negative in 87.3%.<br />Discussion: sensitivity and specificity of the test appear good for IgG, some false positive is expected and low antibody titles in subjects with no disease story should be rechecked with an alternative method. IgM show a good specificity, but the unexpected low percentage of positivity in Emergency Room patients compared to IgG, pose some relevant doubts on the sensitivity of the test.</p>
Biochimica Clinica ; 44(4) 025-026
Variabilità biologica dei parametri dell’esame emocromocitometrico in soggetti sani
Biological variation estimates of complete blood count parameters in healthy subjects
<p>Background: the complete blood count (CBC) is the test more frequently requested in clinical practice. Therefore, estimating the biological variation (BV) of CBC parameters is essential for assessing the analytical performance of hematological analyzers and for enabling accurate data interpretation and appropriate clinical management. This study was aimed to define BV estimates and reference change value (RCV) of CBC parameters.<br />Methods: the study population consisted of 21 healthy volunteers, who had BV of CBC parameters assessed with Sysmex XN. The study protocol, the analytical measurements and the statistical analysis were carried out according to current recommendations of the European Federation for Clinical Chemistry and Laboratory Medicine (EFLM).<br />Results: Within-subject BV ranged between 0,3% for mean cell hemoglobin (MCH) and 19,7% for immature granulocytes (IG), whilst between-subjects BVs ranged between 0,9% for mean corpuscolar haemoglobin concentration (MCHC) and 66,6% for microcytic red blood cells (Micro-R). The RCV ranged between 2,3% for MCH and 73,5% for IG.<br />Conclusion: This study has allowed the estimation of BV of many CBC parameters, some of which have not been currently explored, thus leading the way to use RCV calculated according to time of monitoring and/or differentiated by sex.</p>
Biochimica Clinica ; 43(4) 384-393
Contributi Scientifici - Scientific Papers
L’interferenza dell’emolisi sulla misura dell’insulina
Analytical interference of hemolysis on serum insulin measurement
<p>Insulin is a polypeptide hormone, secretedfrom pancreatic &beta;-cell, involved in the regulation of glucose and lipid metabolism. Insulin measurement is a useful toolto identify some clinical conditions, such as fasting hypoglycemia, some types of diabetes, the presence of insulinresistance. An important pre-analytical aspect that influences the determination of insulin serum concentration is thepresence of hemolysis. In fact, it is well known that insulin is degraded by a protease released by red blood cells afterhemolysis. The aim of this study is to evaluate the interference of hemolysis on insulin measurements performed bya chemiluminescence method. To study the effect of hemolysis on insulin degradation, we added increasingconcentrations of red blood cell hemolysate to a serum pool with known insulin concentration. The reduction of insulinlevels was affected by the degree of hemolysis, by the time elapsed before the assay and by the temperature ofsamples storage. Our results show that insulin values do not decrease significantly (&lt;10%) when hemolysis is &lt;2.0g/L of free hemoglobin (corresponding to H-index=200) if samples are maintained at low temperatures (i.e. in an ice-water slurry) until the assay is performed.</p>
Biochimica Clinica ; 43(3) 273-277
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
Utilità dell’esame citologico del liquido cerebrospinale
Clinical utility of cerebrospinal fluid cytological examination
<p>Cerebrospinal fluid (CSF) of a 64 year old malepatient was sent from the hematology unit to laboratory for cell count and morphology and chemical-physicalexamination. CSF was clear, colourless and with increased total protein concentration. Cell count was first performedin Burker camera with a result of 40/&mu;L; some of the cells showed an abnormal morphology. Our laboratory workflowincludes the CSF examination utilizing an automatic cell counter: it showed a few white blood cells (3/&mu;L), but a highnumber of total cells (64/&mu;L). The morphological evaluation, with cytocentrifugation and May-Grunwald Giemsa stain,identified the elements as mature plasma cells; the result was then confirmed by immunophenotyping.<br />These findings suggest a neurological localization of a multiple myeloma (MM). Actually, the patient had beendiagnosed as IgA lambda MM, with bone involvement that caused progressive loss of walk. Positron EmissionTomography revealed hyperdense areas, but it wasn&rsquo;t able to distinguish between lymphoproliferative disease andthrombotic phlogosis. In spite of the therapy, patient neurological conditions worsened till irreversible coma. He dieda few days later.</p>
Biochimica Clinica ; 43(2) e17-e19
Casi Clinici - Case Report
Importanza dell’utilizzo di Biological Variation Data Critical Appraisal Checklist nel disegno sperimentale di studi di variabilità biologica. Valutazione a confronto di due pubblicazioni sulla variabilità biologica della proteina S100βe dell’enolasi neu
The importance of the Biological Variation Data Critical Appraisal Checklist when designing experimental studies on biological variation. Comparison of two papers reporting biological variation results for S100-β and neuron-specific enolase proteins
<p>The Biological Variation Data Critical Appraisal Checklist (BIVAC) has been designed to evaluate biological variation (BV) studies and the reliability of the associated BV estimates. To illustrate its utility, two studies delivering within-subject BV (CVI) data for S100-&beta; protein and neuron-specific enolase (NSE), markers typically used for melanoma and neuroendocrine tumors, respectively, were appraised using BIVAC. Data from the European Biological Variation Study (EuBIVAS) and the recently published Johnson et al. study (ref n 11) were scored using the 14 BIVAC quality items (QI), with alternatives A, B, C and/or D to verify whether the elements required to obtain reliable BV data, were present and appropriately documented. Grade A indicates compliance with all the QIs and D indicates non compliance. The sizes of the confidence interval (CI) around the CVI estimates were also compared. Johnson&rsquo;s study received a BIVAC grade C, EuBIVAS a grade A. EuBIVAS is a large scale study, with&nbsp;1609 and 1728 results for NSE and S100-&beta;, respectively. In Johnson&rsquo;s study, only 40 results were available. The EuBIVAS CVI estimates [NSE, 10.9% (10.3-11.5); S100-&beta; , 10.2% (9.6-10.7)] were clearly lower than Johnson&rsquo;s CVIs [NSE, 22.1% (9.9-34.3); S100-&beta;, 18.9% (8.5-29.4)]. The overlapping CI between the two estimates are caused by Johnson&rsquo;s CI being about 20 times larger than the corresponding EuBIVAS CI. It is likely that studies that do not comply with all BIVAC QI deliver less reliable, and possibly too high, CVI estimates. Adherence to the BIVAC ensures safe clinical application of BV estimates.</p><p>&nbsp;</p>
Biochimica Clinica ; 43(1) 059-066
Contributi Scientifici - Scientific Paper
Nota all'Editoriale sul Documento della Organizzazione Mondiale della Sanità
Biochimica Clinica ; 43(1) 013
Editoriale - Editorial
Il documento dell’Organizzazione Mondiale della Sanità sulla diagnostica in vitro: una riflessione critica è necessaria
<p>Nello scorso mese di maggio, l&rsquo;Organizzazione Mondiale della Sanit&agrave; (OMS) ha reso disponibile un documento denominato &ldquo;Model List of Essential in Vitro Diagnostics&rdquo; che costituisce un catalogo degli esami di laboratorio che dovrebbero essere universalmente disponibili per la diagnosi e la cura delle pi&ugrave; comuni condizioni cliniche. La pubblicazione di questo documento deve senza dubbio essere salutata come un importante contributo al processo che impegna i governi alla costruzione del repertorio degli esami di laboratorio di base (essenziali), che dovrebbero essere disponibili in ogni tipologia di servizio sanitario e affianca il &ldquo;WHO Model List of Essential Medicines&rdquo; che &egrave; il corrispondente catalogo dedicato ai farmaci.&nbsp;Il documento ha il pregio di riconoscere alla diagnostica di laboratorio un ruolo essenziale per le tre priorit&agrave; strategiche del WHO: migliorare la copertura sanitaria universale, affrontare le emergenze sanitare e promuovere popolazioni pi&ugrave; sane. Una attenta lettura del documento rivela tuttavia alcune criticit&agrave; che ci sembra necessario portare alla attenzione dei laboratoristi Italiani, dopo essere stato oggetto di riflessioni analoghe a livello internazionale.</p>
Biochimica Clinica ; 42(4) 283-284
Editoriale - Editorial
Il Syllabus EFLM per la formazione post-laurea per specialisti in Medicina di Laboratorio: versione n 5 (2018)
<p>The European Federation of Clinical Chemistry and Laboratory Medicine syllabus for postgraduate education and training for Specialists in Laboratory Medicine: version 5 &ndash; 2018. Although laboratory medicine practise varies across the European Union&rsquo;s (EU) member states, the extent of overlap in scope is such that a common syllabus describing the education and training associated with high-quality, specialist practise can be identified. In turn, such a syllabus can help define the common set of skills, knowledge and competence in a Common Training Framework (CTF) for non-medical Specialists in Laboratory Medicine under EU Directive 2013/55/ EU (The recognition of Professional Qualifications). In meeting the requirements of the directive&rsquo;s CTF patient safety is particularly enhanced when specialists seek to capitalise on opportunities for free professional migration across EU borders. In updating the fourth syllabus, the fifth expands on individual discipline requirements, new analytical techniques and use of statistics. An outline structure for a training programme is proposed together with expected responsibilities of trainees and trainers; reference is provided to a trainee&rsquo;s log book. In updating the syllabus, it continues to support national programmes and the aims of EU Directive 2013/55/EU in providing safeguards to professional mobility across European borders at a time when the demand for highly qualified professionals is increasing in the face of a disparity in their distribution across Europe. In support of achieving a CTF, the syllabus represents EFLM&rsquo;s position statement for the education and training that underpins the framework.</p><p>&nbsp;</p>
Biochimica Clinica ; 42(3) 247-262
Documenti - Documents
Breve curriculum del Prof. Giovanni Ceriotti
F. Ceriotti  | 
Biochimica Clinica ; 42(1) 85
Notizie SIBioC - SIBioC News
Appropriatezza della richiesta di esami ed esiti clinici: il caso delle malattie renali, tiroidee e della celiachia
Appropriateness of test request and clinical outcome: the example of kidney, thyroid and coeliac disease
<p>This document analyzes the topic of appropriateness of test request. It is organized in 4 parts. The first deals with the theme of appropriateness, the consequences of insufficient or excessive test request and the need to balance guideline indications with the clinical need of a single patient. The other 3 parts present the cases of thyroid, chronic kidney and coeliac disease. With regard to the thyroid function, population screening, excluding neonates, is not recommended; on the contrary, it is highly recommended to evaluate the thyroid function in any individual with even only a minimal clinical suspect. The thyrotropin (TSH) is the test of choice with reflex free T4 and free T3, according to specific algorithms. The contemporaneous measurement of free FT3, free FT4 and TSH, except for specific cases, should be discouraged due to the high frequency of unjustified abnormal findings. Anti-thyroperoxidase antibodies are the test of choice for autoimmune thyroid diseases. In chronic kidney disease (CKD), the estimated glomerular filtration rate (eGFR) based on serum creatinine in most cases is the best indicator of renal function, provided that creatinine is measured with the accurate enzymatic method. In borderline situations, a confirmatory eGFR calculation based on cystatin C is recommended. Urinary albumin, expressed as albumin/creatinine ratio, is an essential complement for CKD staging. The diagnosis of coeliac disease requires integration between clinical, histological and serological data. The anti-transglutaminase IgA is the test of choice; only when an IgA deficit is present, the test to be used is IgG antigliadin deamidate peptides. The genetic HLA DQ2/DQ8 test is indicated for screening of subjects at risk: if negative, coeliac disease can be excluded.</p>
Biochimica Clinica ; 41(3) 266-285
Documenti - Documents
Esami di laboratorio in Pronto Soccorso: una proposta di consenso SIBioC - Medicina di Laboratorio e Academy of Emergency Medicine and Care
Laboratory tests in the Emergency Department: a consensus document by SIBioC-Medicina di Laboratorio and the Academy of Emergency Medicine and Care
<p>Laboratory diagnostics in the emergency setting encompasses the identification of appropriate testing according to specific acute conditions. Since the pathway of ordering tests in the Italian Emergency Departments (EDs) is rather heterogeneous, SIBioC-Medicina di Laboratorio and the Academy of Emergency Medicine and Care designed a survey aimed to generate consensus pertaining to appropriate laboratory tests in most frequent acute conditions. A questionnaire including a panel of laboratory tests was administered to 8 representative members of each of the two societies, who were asked to provide a score between 1 and 3 for the various tests, where a score of 1 entailed &ldquo;highly recommended&rdquo;, 2 &ldquo;recommended in specific conditions&rdquo; and 3 identified &ldquo;highly discouraged&rdquo; tests. The results of the questionnaire are shown as mean (&plusmn;SD) of individual responses, thus allowing to define a scale of priority comprised between &ldquo;highly recommended&rdquo; and &ldquo;highly discouraged&rdquo;. Overall, 24 tests were classified as &ldquo;highly recommended&rdquo;, whereas 6 were &ldquo;highly discouraged&rdquo;. The remaining 16 tests were classified as &ldquo;somehow recommended&rdquo; or &ldquo;somehow discouraged&rdquo;. In the expectations of the two societies, this document may represent a first step towards harmonizing the laboratory test ordering in Italian EDs.</p>
Biochimica Clinica ; 41(2) 183-188
Documenti SIBioC - SIBioC Documents
Intervalli di riferimento standardizzati della fosfatasi alcalina sierica in soggetti pediatrici
Traceable reference intervals for alkaline phosphatase in serum of pediatrics
<p>The definition of pediatric reference intervals for alkaline phosphatase (ALP) in serum represents a challenging task due to the high and variable concentrations of this enzyme in children compared to adults. Aim of this work was the establishment of ALP pediatric reference intervals in an Italian population using an indirect method and traceable assays for ALP measurements. A data mining approach involving 12 centers was applied. To verify the analytical quality of the participating centers, 3 pools with ALP target values established by the reference procedure were distributed and analyzed by the centers at the beginning and at regular intervals during the data collection period (May-September 2016). When needed (deviation from target &gt;2%), the results obtained on the 3 pools were used to recalculate ALP results of reference individuals, thus making them traceable to the reference procedure. Each center selected from its database the ALP results of outpatients, aged 0-20 years, excluding those from oncological or orthopedic clinics and the results from subjects that repeated the test more than once. Very high and very low ALP values were investigated for excluding liver, kidney or bone disease. The results were elaborated with a modification of the algorithm proposed by Concordet et al. 4824 ALP values were collected (2372 from females and 2452 from males, respectively). The lower reference limit was the same for boys and girls &lt;12 years old (140 U/L), reaching down the adult concentrations at 16 years for females and 18 years for males. The pubertal peak was at 9-11 years for females (430 U/L) and 12-14 years for males (465 U/L).</p>
Biochimica Clinica ; 41(2) 166-174
Contributi scientifici - Scientific papers
Attività di SIBioC - Medicina di Laboratorio e soddisfazione dei soci: risultati di un questionario
Survey on the satisfaction of SIBioC members on the society’s activities
S. Buoro  |  M. Ciaccio  |  F. Ceriotti  | 
<p>This report presents the results of a survey performed on Oct-Nov 2015 on SIBioC member satisfaction. The survey addressed event attendance/received value, networking opportunities and overall benefit of SIBioC membership. An on-line questionnaire was sent to all SIBioC members through the web-based SurveyMonkey platform and the resulting database was statistically analyzed. The respondents (514 out of 2000 members) can be considered a representative sample of the associates, since different professional branches were represented proportionally. The large majority of respondents were familiar with SIBioC Newsletter and expressed a positive opinion on it. 71% of the respondents declared to access the official website from 1 to 5 times per month. Finally, 50,8% of respondents declared that they were aware of the existence of Lab Tests Online (LTO) website, with the majority of them (78.2%) being satisfied with it. Overall, the survey data showed a good level of satisfaction with SIBioC educational offer. The only aspect not completely positive was the limited knowledge of LTO, despite the large investment made on it by the society. Regarding the current scenario of reorganization of the laboratory network, many respondents addressed specific requests related to both enhancing the ad hoc education and improving the dialogue with institutions and other scientific societies. In these two fields, SIBioC is currently putting large efforts. Overall, the survey gave a positive feed-back stimulating the SIBioC management to further ameliorate the service to members, with the aim of contributing in continuously improving the quality of laboratory services and then the patient care.</p>
Biochimica Clinica ; 41(1) 096-101
Documenti - Documents
Valutazione dell’esattezza della misura della fosfatasi alcalina sierica in un gruppo di laboratori italiani
Evaluation of the trueness of serum alkaline phosphatase (ALP) measurement in a group of Italian laboratories
<p>The reference measurement procedure for ALP published in 2011 by the IFCC allowed to define the metrological traceability chain for the standardization of ALP measurement. This paper reports the results of an EQA experiment conducted to evaluate the level of ALP standardization among different Italian laboratories enrolled for a scientific project with the final aim to derive ALP traceable reference intervals for pediatric population. Three frozen serum pools with a target value assigned by the IFCC reference procedure were distributed to 13 centers and analyzed in triplicates for 3 different days. Only 3 laboratories averagely fulfilled the desirable goal of bias (&le;&plusmn;5.5%) at all 3 concentrations (59.9 U/L, 186.9 U/L and 401.5 U/L), but only one provided data with a dispersion always within the uncertainty of the target result. The different ability to meet the goal clearly depended on the analytical system used. Focusing on the two most used analytical platforms, the Cobas systems (Roche Diagnostics) underestimated the ALP values, while the AU systems (Beckman Coulter) overestimated them. The regression parameters between the average values obtained by laboratories and the target values indicate that it would be possible to correct the results of all analytical systems and make them unbiased by a simple recalibration approach. The analysis of the commercial calibrator package inserts of the IVD companies involved in this study showed that, with the exception of Roche still aligned to the old Tietz method published in 1983, all companies offer at least two options, sometimes (e.g., Beckman AU) both not in line with the recommended standardization approach.</p>
Biochimica Clinica ; 41(1) 064-071
Contributi scientifici - Scientific papers
La diagnostica di laboratorio delle dislipidemie
The laboratory diagnosis of dyslipidemia
<p>Dyslipidemias represent a major contributor to cardiovascular risk in Western countries, including Italy, that can be modified. After examining familial dyslipidemias and describing the essential issues for clinical and laboratory diagnostics, the paper considers the laboratory testing in detail. The preanalytical sources of variability (biological, sample collection and handling) are reviewed and essential indications to reduce them are given. About the analytical variability, the paper examines the methods routinely used for measuring the basic lipid parameters (total, LDL and HDL cholesterol, triglycerides and apolipoproteins A-I and B) and describes the state of art of the standardization of these analytes. The last section of the document deals with the reporting of laboratory results. The main indications of the document are the following: a) report the desirable values established by the European guidelines besides the measured concentrations; b) make always clear that the reported values are decisional cut points and not reference limits; c) add a note stating that the reported desirable values refer to individuals at low risk; d) report as critical values lipid concentrations deserving rapid clinical attention, i.e., total cholesterol, &ge;8,00 mmol/L (310 mg/dL); LDL cholesterol, &ge;4,90 mmol/L (190 mg/dL); triglycerides, &ge;10,0 mmol/L (880 mg/dL).</p>
Biochimica Clinica ; 40(4) 338-346
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
Il progetto pilota SIBioC di VEQ della misura dell’emoglobina glicata
Pilot SIBioC EQAS project on glycated hemoglobin measurement
<p>Two fresh blood samples collected with EDTA&nbsp;were distributed by courier in December 2014 to 206 Italian laboratories asking for the determination of their HbA<sub>1c</sub> concentrations. Target HbA<sub>1c</sub> values were assigned by the IFCC reference measurement procedure based on HPLC capillary&nbsp;electrophoresis. The results, collected from 193 laboratories using analytical systems mainly from five&nbsp;manufacturers (Bio-Rad Laboratories, A. Menarini Diagnostics, Roche Diagnostics, Sebia and Tosoh), showed a&nbsp;global variability (in terms of CV) of 5.3% and 3.8% at HbA<sub>1c</sub> values of 37.4 mmol/mol (sample 1) and 62.0 mmol/mol&nbsp;(sample 2), respectively. Globally, 84% of the participants reported HbA<sub>1c</sub> results within the total allowable error (TE)&nbsp;of 8.6% (sample 1) and 93% for sample 2. These percentages decreased to 70% and 77%, respectively, when using&nbsp;a goal for the allowable TE of 6.0% as criterion. Inter-laboratory CVs, calculated per group of methods, were between&nbsp;3.3% and 5.0% and between 2.2% and 3.7% for sample 1 and 2, respectively. Tosoh users registered the smaller&nbsp;inter-laboratory CV in sample 1 and Sebia&rsquo;s in sample 2. With regard to trueness, all methods had a mean bias &le;2.8%&nbsp;respect to the target values, with the exception of Tosoh (bias of +6.1% and +5.8%, for samples 1 and 2, respectively).</p>
Biochimica Clinica ; 39(6) 568-574
Contributi scientifici - Scientific Papers
La stima dell'incertezza delle misure nel laboratorio clinico
Measurement uncertainty calculation in clinical laboratories
<p>The result of a measurement is only an estimate of&nbsp;the value of the measurand and it is complete only when accompanied by a statement of the measurement uncertainty.&nbsp;The ISO 15189 standard requires that &ldquo;the laboratory shall determine measurement uncertainty for each measurement&nbsp;procedure&rdquo;. The approach to calculate the measurement uncertainty proposed by the &ldquo;Guide to the expression of&nbsp;uncertainty in measurement&rdquo; (GUM) requires the quantification of every source of variability to sum them up for the&nbsp;final calculation (&ldquo;bottom-up&rdquo; approach). To overcome inherent difficulties in the systematic application of this approach&nbsp;in a clinical laboratory, a &quot;top-down&quot; approach is proposed, through the calculation of measurement uncertainty from&nbsp;already existing data of IQC. The proposed approach is checked by applying it to the IQC data for serum glucose and&nbsp;creatinine measurements collected from 19 clinical laboratories. Different approaches to cope with the issue of the&nbsp;estimate of systematic error (bias) are proposed, based either on value-assigned trueness control/reference materials,&nbsp;on the mean value of the employed material defined by the laboratory at the start of the IQC program or on the peer&nbsp;group mean of an interlaboratory program material. The availability of a standardized way to estimate the measurement&nbsp;uncertainty provides a tool to evaluate the analytical quality of results and it allows comparison of the quality of results&nbsp;made available by different laboratories.</p>
Biochimica Clinica ; 39(2) 108-115
Contributi scientifici - Scientific Papers
Standardizzazione e armonizzazione: SIBioC in prima linea
Standardization and harmonization: SIBioC at the front line
F. Ceriotti  | 
<p>Standardization and harmonization are probably the&nbsp;most relevant challenge for Laboratory Medicine. Rapidly available and precise results can indeed be of very limited&nbsp;value if they cannot be compared with each other, are produced on a wrong material or within an inappropriate&nbsp;diagnostic workflow. SIBioC is starting a strategy devoted to develop guidelines and to produce scientific evidence in&nbsp;order to improve harmonization of the total testing process. This paper summarizes all initiatives in the field that&nbsp;SIBioC has implemented, is developing or will try to develop in the foreseeable future to increase harmonization, by&nbsp;categorizing them in the different phases of the testing process, from pre-pre-analytical to post-post-analytical phase.&nbsp;A list of the proposed and programmed actions is further presented. An harmonized context will increase the value of&nbsp;laboratory results facilitating their interpretation and thus improving the patient&rsquo;s outcome.</p>
Biochimica Clinica ; 39(1) 048-055
Documenti - Documents
SIBioC e società internazionali di Medicina di Laboratorio: mai come ora
SIBioC and International Societies of Laboratory Medicine: now more than ever
F. Ceriotti  | 
Biochimica Clinica ; 38(1) 77-78
Notizie SIBioC - SIBioC News
L’importanza della qualità analitica
The value of analytical quality
F. Ceriotti  | 
Biochimica Clinica ; 37(6) 452-453
Editoriale - Editorial
Un aggiornamento sulle attività del Comitato “Reference systems for enzymes” (C-RSE) dell’IFCC
An update on the activities of IFCC Committee of “Reference systems for enzymes” (C-RSE)
F. Ceriotti  | 
Biochimica Clinica ; 37(3) 252
Notizie SIBioC - SIBioC News
Valutazione dell’impatto del processo di standardizzazione sulla qualità della misura della creatininemia nei laboratori italiani
Evaluation of the impact of standardization process on the quality of serum creatinine determination in Italian laboratories
<p style="text-align: justify;">Evaluation of the impact of standardization process on the quality of serum creatinine determination in Italian laboratories. Creatinine determination in serum is a key indicator of kidney glomerular function. A reference measurement system for standardization of creatinine measurements is now available and virtually all IVD manufacturers have aligned their creatinine assays to this system. The aim of this work was to verify if and how these standardization efforts have improved the state of the art of creatinine determination in Italy through the analysis of Prolarit EQAS results using control materials with target values assigned by a traceable method (enzymatic assay calibrated against the NIST SRM 967). Results obtained during 2006, 2010, and 2011 schemes by participating laboratories showed a general good alignment at creatinine concentrations <span style="font-family: symbol;">&#61566;</span>2.00 mg/dL, with 2011 results &#8211; except for one method group &#8211; well inside the desirable bias (<span style="font-family: symbol;">&#61617;</span>4%). At higher concentrations, whereas the overall bias was small in 2010, for some groups using alkaline picrate (AP) methods it became significantly negative in 2011. The performance markedly worsens at creatinine physiologic concentrations, where a significant positive bias (up to <span style="font-family: symbol;">&#61566;</span>20%) is still present for most of the AP-based analytical systems. Unexpectedly, with few exceptions, no evident improvement in individual assay bias was noted from pre- (2006) to post-standardization (2011) periods. The enzymatic method groups were the only always presenting an acceptable bias for all concentration levels, in addition to showing the lowest between-laboratory variability. The number of laboratories using enzymatic methods, however, still remains only 7% of the total. In conclusion, our EQAS performance data indicate that most of the current "standardized" creatinine methods based on AP reaction do not perform well, mainly at the lower creatinine concentrations. This inaccuracy of creatinine measurements can adversely impact the estimation of glomerular filtration rate by equations and the evaluation of kidney function in pediatrics.</p>
Biochimica Clinica ; 36(6) 414-424
Contributi Scientifici - Scientific Papers
Ottimizzazione di un metodo di misura della lipasi pancreatica con 1,2-o-dilauril-rac-glicero-3-glutarico (6-metilresorufina) estere come substrato
Optimization of a 1,2-o-dilauryl-rac-glycero-3-glutaric acid (6-methylresorufin) ester method for the measurement of pancreatic lipase catalytic activity.
L. Politi  |  F. Ceriotti  | 
<p>The measure of the catalytic activity of lipase in serum is a good indicator of acute pancreatitis. Today there is not an accepted reference method. Aim of this work was to optimize a method for measurement of catalytic activity of pancreatic lipase in serum, which could have the necessary characteristics to serve as a candidate reference method. Serum pools with different concentrations of lipase in native and inactivated form (heat inactivation at 56 &#176;C for 1 h) and control materials were used as samples. Optimal concentrations in the final reaction mixture were obtained through a series of experiments. Optimization was reached when higher catalytic activity and lower nonspecific signal were obtained. The following conditions were tested: buffer type and concentration, concentration of bile salts (taurodeoxycholate and deoycholate), concentration of calcium chloride, effect of different surfactants, substrate concentration, colipase concentration, and pH. The optimization experiments lead to the following reaction conditions (concentrations in the final reaction mixture): pH, 8.0; taurodeoxycholate, 21,9 mmol/L; deoxycholate, 5,28 mmol/L; calcium chloride, 6,43 mmol/L; colipase, 2,24 mg/L; 1,2-o-dilauryl-rac-glycero-3-glutaric acid (6-methylresorufin) ester, 0,11 mmol/L; Triton X-100, 0,75 g/L. Using the herein described measurement conditions, CV ranging from 1,4% to 2,9% were obtained. A comparison with the assay used in our clinical laboratory using the same substrate gave the following regression equation: y=1.56x + 2,4 U/L, r2=0.982.</p>
Biochimica Clinica ; 36(3) 177-186
Contributi Scientifici - Scientific Papers
Teoria e pratica degli intervalli di riferimento riferibili
Theory and practice of traceable reference intervals
<p>An issue associated with standardization efforts is the need to develop useful reference intervals. Lack of proper reference intervals may indeed hamper the implementation of standardization in Laboratory Medicine as standardization can modify analyte results and, without adequate reference intervals, this can impair the result interpretation. Once defined, reference intervals obtained with analytical procedures that produce results traceable to the corresponding reference system can be transferred among laboratories, providing that they use commercial assays that produce results traceable to the same reference system and populations have the same characteristics. Multicenter studies are needed for a robust definition of traceable reference intervals, using experimental protocols that include well defined prerequisites. Particularly, employed methods must produce results that are traceable to the reference system for that specific analyte. Thus, the trueness of laboratories producing reference values should be verified and, if necessary, experimental results corrected in accordance with correlation results wit h the selected reference. If requirements in the adoption of traceable reference intervals are fulfilled, the possibility of providing reference intervals that are applicable to any laboratory, able to produce results traceable to the reference system, is realistic. The definition of traceable reference intervals should hopefully cause the disappearance of different reference intervals employed for the same analyte, providing more effective information to clinicians.</p>
Biochimica Clinica ; 36(3) 171-176
Rassegna - Reviews
Funzioni e compiti del laboratorio nell’ospedale moderno: alcune considerazioni 40 anni dopo
Functions and tasks of the clinical laboratory in the modern hospital: some thoughts 40 years later.
F. Ceriotti  | 
<p>This paper comments the document prepared by Giovanni Ceriotti and Carlo Riga as opening lecture of the 2nd SIBioC Congress held in Padua in May 1972.Some key messages of that document still remain actual 40 years later: the central role of the medical laboratory for the clinical diagnosis, its essential support to the evidence-based medicine, and its pivotal function in the progress of medicine, being the privileged site for what we now call &#8220;translational research&#8221;. Unfortunately, the realization of some aspects, that were seen as ready to start in the &#8216;70s, is still under development nowadays. In particular, the result standardization is still far from a capillary implementation. Moreover, despite its enormous development in terms of number and types of performed tests, the clinical laboratory did not appear to assume the importance that was foreseen 40 years ago and seems to loose attractive for the new generations of students and graduates. Clinical laboratory professionals, driven by economic pressure and the enormous development of technology, seemed to dedicate more attention and efforts to organizational aspects, productivity and automation than to clinical research, clinical consultation and analytical quality, thus reducing the role of laboratory in clinical research and consequently its actracting power for young scientists.</p>
Biochimica Clinica ; 36(1) 29-32
Opinioni - Opinions
La fase preanalitica nella misura del [-2]propsa e dell'Indice di Salute Prostatica
Pre-analytical phase of [-2]proPSA measurement and Prostate Health Index calculation
Biochimica Clinica ; 35(5) 373
Linee guida per la gestione dei programmi di Valutazione Esterna di Qualità
Guidelines for External Quality Assessment Scheme organization
Biochimica Clinica ; 35(2) 107
Standardizzazione in enzimologia clinica: una sfida per la teoria della riferibilità metrologica
Standardization in clinical enzymology: a challenge for the theory of metrological traceability
Biochimica Clinica ; 34(2) 96
Determinazione della creatinina: per i laboratori è tempo di agire
Measurement of creatinine in clinical laboratories: it's time for action
F. Ceriotti  | 
Biochimica Clinica ; 34(1) 9