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BC: Articoli scritti da F. Braga

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
Armonizzazione in Medicina di Laboratorio
Harmonization in Laboratory Medicine
Biochimica Clinica ; 39(6) 546-547
Editoriale - Editorial
Riferibilità metrologica come strumento per la standardizzazione delle misure in Medicina di Laboratorio
Metrological traceability as a tool to standardize measurements in Laboratory Medicine
<p>Basics for the correct application of the concept of metrological traceability in laboratory measurements are the univocal definition of the measurand and of an unbroken metrological traceability chain, the demonstration of the commutability of calibration materials, the correction of the measurement bias and the estimate of combined uncertainty at each level of the metrological chain. In vitro diagnostics (IVD) manufacturers should ensure traceability of their analytical systems to recognized higher-order references (materials and/or methods) and estimate the combined uncertainty of calibrators. End-users should check the IVD traceability through the verification that control materials of analytical systems are in the manufacturer&rsquo;s declared validation range and through the organization of EQAS that meet metrological criteria. Separately, they should also estimate the contribution to measurement uncertainty by random effects. Main unsolved issues are the lack of full information about sources of traceability and uncertainty of commercial calibrators, the lack of objective analytical specifications and the need to properly define and use &lsquo;traceable&rsquo; reference intervals.</p>
Biochimica Clinica ; 39(6) 551-558
Rassegne - Reviews
Un “Task and Finish Group” dell’”European Federation of Clinical Chemistry and Laboratory Medicine” (EFLM) per la creazione di un nuovo “database” elettronico per i dati di variabilità biologica
First report from the EFLM Task and Finish Group for the Biological Variation Database
F. Braga  | 
Biochimica Clinica ; 39(3) 225-226
Notizie SIBioC - SIBioC News
La misura delle proteine totali per la quantificazione del crioprecipitato è “evidence-based”?
Is the total protein measurement for cryocrit quantification evidence-based?
F. Braga  |  A.  Dolci  |  M. Panteghini  | 
Biochimica Clinica ; 38(1) 73
Lettere all'Editore - Letters to the Editor
Report dal congresso satellite EuroMedLab sulle proteine plasmatiche
Report from the EuroMedLab Satellite Meeting on plasma proteins
F. Braga  | 
Biochimica Clinica ; 37(6) 508-509
Notizie SIBioC - SIBioC News
Verifica della riferibilità metrologica dei dispositivi medico-diagnostici in vitro: responsabilità e strategie
Verification of in vitro medical diagnostics (IVD) metrological traceability: strategies and responsibilities
<p>To&nbsp;be accurate and equivalent laboratory results should be traceable to higher-order references. Furthermore, their&nbsp;analytic quality should fulfil acceptable measurement uncertainty as defined to fit the intended clinical use. To this&nbsp;aim, IVD manufacturers should define a calibration hierarchy to assign traceable values to their system calibrators&nbsp;and to fulfil during this process uncertainty limits for calibrators that should represent a proportion of the uncertainty&nbsp;budget allowed for clinical laboratory results. It is important that end-users may know and verify how manufacturers&nbsp;have implemented the traceability of their calibrators and estimated the corresponding uncertainty. Currently, the full&nbsp;information about traceability and uncertainty of calibrator is not available as manufacturers only provide the name of&nbsp;higher-order reference material and/or procedure to which the assay calibration is traceable without any description&nbsp;of steps and their corresponding uncertainty of the implemented traceability chain. Important post-market tools for&nbsp;IVD traceability surveillance are related to the verification by clinical laboratories of the consistency of declared&nbsp;performance during daily operations performed in accordance with the manufacturer&rsquo;s instructions and the&nbsp;organization of appropriately structured EQAS. The former activity should be accomplished by analyzing system&nbsp;control materials and confirming that current measurements are in the manufacturer&rsquo;s established control range. With&nbsp;regard to EQAS, it is mandatory that target values to materials are assigned with reference procedures by an&nbsp;accredited reference laboratory, that materials are commutable and a clinically allowable inaccuracy for participant&rsquo;s&nbsp;results is defined in order to prove the suitability of laboratory measurements in clinical setting.</p>
Biochimica Clinica ; 37(6) 470-478
Opinioni - Opinions
Variabilità biologica delle catene leggere libere delle immunoglobuline nel siero
Biologic variation of immunoglobulin free light chains in serum
<p>The measurement of serum <span style="font-family:symbol">k</span> and <span style="font-family:symbol">l</span> free light&nbsp;chains (FLC) and <span style="font-family:symbol">k</span>/<span style="font-family:symbol">l</span> FLC ratio calculation are recommended for screening, prognostic evaluation and monitoring of&nbsp;multiple myeloma and related plasma cell disorders. Given the lack of reliable data available in literature, in this study&nbsp;we assessed biologic variability components of FLCs and FLC ratio by an accurately designed protocol. We collected&nbsp;five blood specimens from each of 21 healthy volunteers (9 men and 12 women; age range, 23-54 years) on the same&nbsp;day, every two weeks for two months. Serum specimens were stored at -80 &deg;C until analysis and analyzed in a single&nbsp;run in duplicate using a SPAPLuS immunoturbidimetric platform and Freelite reagents (The Binding Site). Data were&nbsp;analyzed by ANOVA. Serum <span style="font-family:symbol">l</span> FLC concentrations were significantly (P &lt;0.01) higher in men. The inter-individual&nbsp;variance of <span style="font-family:symbol">l</span> FLC was higher than that of <span style="font-family:symbol">k</span> FLC. Within- and between-subject CVs were 8.1% and 14.1% for <span style="font-family:symbol">k</span> FLC,&nbsp;7.0% and 27.5% for <span style="font-family:symbol">l</span> FLC, and 4.5% and 15.3% for FLC ratio. All parameters had marked individuality showing that&nbsp;the use of population-based reference intervals could be inadequate for test interpretation. The reference change&nbsp;value was between 20% and 30% depending from the assay imprecision. Desirable analytical goals for imprecision&nbsp;(CV), bias and total error were &lt;4.0%, &plusmn;4.1% and &plusmn;10.7% for <span style="font-family:symbol">k</span> FLC, &lt;3.5%, &plusmn;7.1% and &plusmn;12.9% for <span style="font-family:symbol">l</span> FLC, and&nbsp;&lt;2.3%, &plusmn;4.0% and &plusmn;7.7% for FLC ratio.</p>
Biochimica Clinica ; 37(5) 376-382
Contributi Scientifici - Scientific Papers
Serum human epididymis protein 4 vs. carbohydrate antigen 125 for ovarian cancer diagnosis: a systematic review
<p>Human epididymis protein 4 (HE4) measurements in serum have been proposed for improving the specificity of&nbsp;laboratory identification of ovarian cancer (OC). This study sought to critically revise the available literature on the&nbsp;comparison between the diagnostic accuracy of HE4 and carbohydrate antigen 125 (CA-125) to provide evidence of&nbsp;HE4 additional clinical value. Literature search was undertaken on electronic databases and references from&nbsp;retrieved articles, and articles analyzed according to predefined criteria. Meta-analyses for HE4 and CA-125&nbsp;biomarkers with odds ratio (OR), diagnostic sensitivity, specificity, positive (LR+) and negative (LR&ndash;) likelihood ratios&nbsp;as effect sizes were performed. Sixteen articles were originally included in meta-analyses, but two for HE4 and one&nbsp;for CA-125 were eliminated as outliers. Furthermore, for HE4 a publication bias was detected. ORs for both HE4&nbsp;(37.2, 95% CI: 19.0-72.7, adjusted for publication bias) and CA-125 (15.4, 95% CI: 10.4-22.8) were significant,&nbsp;although in a heterogeneous set of studies (P &lt;0.0001). By combining sensitivity and specificity, the overall LR+ and&nbsp;LR&ndash; were 13.0 (95% CI: 8.2-20.7) and 0.23 (95% CI: 0.19-0.28) for HE4 and 4.2 (95% CI: 3.1-5.6) and 0.27 (95% CI:&nbsp;0.23-0.31) for CA-125, respectively. HE4 measurement seems to be superior to CA-125 in terms of diagnostic&nbsp;performance for identification of OC in women with suspected gynecological disease. Due to the high prevalence of&nbsp;OC in post-menopausal women and the need of data focused on early tumor stages, more studies tailored on these&nbsp;specific subsets are needed.</p>
Biochimica Clinica ; 37(3) 179-189
Rassegne - Reviews
Standardizzazione della misura e traguardi analitici per l’emoglobina glicata
Measurement standardization and analytical goals for glycated hemoglobin
<p><span style="font-size:small">Glycated hemoglobin (HbA<span style="font-size:x-small">1c</span>) plays a key role in diagnosing diabetes and monitoring the glycemic state. To guarantee the reliability of its measurement at global level, IFCC has defined a reference measurement system, based on the definition of the measurand as hemoglobin molecules having a special hexapeptide in common, which is the stable adduct of glucose to the N-terminal valine of the hemoglobin b-thechain. In addition to the traceability of HbA1c results to the reference </span>system, the establishment of analytical goals to make HbA<span style="font-size:x-small">1c </span><span style="font-size:small">measurements clinically reliable becomes crucial. </span>However, allowable goals will depend on the assay specificity (i.e., selectivity) and, consequently, on units in which <span style="font-size:small">HbA<span style="font-size:x-small">1c</span> results are expressed [mmol/mol for IFCC-aligned systems or % for National Glycohemoglobin Standardization Program (NGSP) converted numbers]. In this regard, analytical goals derived from biologic variability studies in which </span><span style="font-size:small">the determination of HbA<span style="font-size:x-small">1c</span> has been carried out by an assay providing the same selectivity for the measurand as </span><span style="font-size:small">defined </span>by the IFCC are recommended. Only these targets should be used for evaluating the performance of commercial assays traceable to the IFCC system and of clinical laboratories using them through appropriately structured quality controls. Analytical systems following different calibration hierarchies (e.g., the NGSP-aligned assays) will require different analytical goals.</p>
Biochimica Clinica ; 37(2) 100-107
Opinioni - Opinions
Etica e metodologia di scrittura di un lavoro scientifico
Publication ethics and scientific writing
<p>Ethic issues and the structure of manuscripts are two main aspects when writing a research paper in the biomedical field with the aim to submit it to a scientific journal for publication. Considering publication ethics, the integrity of the scientific writing is under the responsibility of authors, reviewers, and editor of the journal and should be maintained across the entire process of publication. The authors&rsquo; responsibility includes unequivocal transgression (falsification of data, plagiarism, authorship, conflict of interest), which cannot be tolerated, and undesirable practice (self plagiarism, redundant publication) as well. The reviewers&rsquo; responsibility includes conflict of interest and confidentiality. Among the journal editor&rsquo;s responsibilities, there are conflict of interest, publication bias, willingness of publishing complaints, clarifications and apologies. A scientific article should usually have a definite structure, made up of different sections. Here suggestions are given on how to find an appealing &ldquo;Title&rdquo;, how to prepare a comprehensive &ldquo;Abstract&rdquo;, how to cope with the &ldquo;Introduction&rdquo;, how to improve the description of employed &ldquo;Methods&rdquo;, how to present data in the &ldquo;Results&rdquo; section, and how to better organize the results &ldquo;Discussion&rdquo;. Our experience as editors of this journal suggests that our colleagues should be more aware of both ethical aspects and correct procedures to follow before starting to write a scientific paper in order to prevent the rejection of their work.</p>
Biochimica Clinica ; 37(1) 40-47
Opinioni - Opinions
Saturazione della transferrina: c’era una volta il test
Transferrin saturation: once upon a time there was the test
D. Szoke  |  F. Braga  |  A.  Dolci  |  M. Panteghini  | 
<p>Despite the growing interest in hepcidin and other new biomarkers, guidelines and clinical pathways continue to recommend traditional markers, such as serum transferrin saturation (TS) and ferritin, as laboratory tests for the diagnostic evaluation of iron-related disorders. Here we aimed to critically evaluate the diagnostic role of TS relying on the highest level of available evidence by a comprehensive literature search. The role of TS in iron deficiency (ID) and iron overload (IO) syndrome as well as a risk marker was evaluated. The low accuracy of TS in the diagnosis and management of ID conditions does not permit recommending its use, even if recently published guidelines still consider the TS investigation as a complementary test for serum ferritin. If an IO is suspected, TS is often used even if it may not be the best test for detecting this condition. Nevertheless, clinical guidelines strongly recommend the use of TS as a first-level test for performing genetic&#160;diagnosis of hereditary hemochromatosis. Recent data indicating elevated TS as a risk factor for diabetes mellitus,cancer, and total mortality may provide useful additions to the debate over whether or not screen for IO using TS.</p>
Biochimica Clinica ; 36(5) 339-348
Rassegna - Reviews
Quando l’urina diventa rossa: un’inattesa macroematuria
If urines become red: an unexpected case of gross hematuria.
D. Szőke  |  C. Valente  |  F. Braga  |  A. Dolci  |  M. Panteghini  | 
<p>The physiological colour of urine is usually yellow. Urine discoloration is a common situation in clinical practice and a variety of colours may be seen. When a patient complains of green or blue urine, there is no confusion with a pathological origin. However, when the urine is red, the first thought is usually hematuria leading to anxiety for patient himself and for physicians too. We present a case of a 54 years old man presenting with asymptomatic apparent gross hematuria ruled out by chemical urinalysis and visual microscopic evaluation of the sediment showing neither hemoglobin nor red blood cells in his urine specimen. Possible causes of red urine not related to presence of blood are critically presented and discussed.</p>
Biochimica Clinica ; 36(2) 139-143
Casi Clinici - Case Report
Il "Joint Committee for Traceability in Laboratory Medicine" (JCTLM): una cooperazione internazionale per promuovere la standardizzazione dei risultati in Medicina di Laboratorio
The Joint Committee for Traceability in Laboratory Medicine (JCTLM): a global cooperation to promote the standardisation of test results in Laboratory Medicine
Biochimica Clinica ; 35(5) 377
Impact of the implementation of highly sensitive cardiac troponin T assay in a university hospital setting
Impact of the implementation of highly sensitive cardiac troponin T assay in a university hospital setting
Biochimica Clinica ; 35(4) 301
Valutazione della sensibilità diagnostica per l'infarto miocardico senza sopraslivellamento del tratto ST (NSTEMI) di due metodi ad alta sensibilità per la troponina cardiaca
Evaluation of the sensitivity of two highly sensitive troponin assays for early detection of non ST-elevation myocardial infarction (NSTEMI).
Biochimica Clinica ; 35(3) 186