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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 M. Panteghini

Determinazione della concentrazione dell’inibitore C1 esterasi nel siero: un invito alla standardizzazione
Determination of C1-esterase inhibitor concentration in serum: a call for standardization
I. Infusino \| C. Timpanaro \| D. Szoke \| M. Panteghini \|

Biochimica Clinica ; 42(1) 79-81 Lettere all'Editore - Letters to the Editor

Valutazione del sistema Optilite™ per la misura delle catene leggere libere delle immunoglobuline nel siero
Evaluation of the Optilite™ system for the determination of immunoglobulin free light chains in serum (sFLC)
I. Infusino \| S. Borille \| M. Panteghini \|
<p>The measurement of sFLC<span style="font-size:14px"><span style="color:rgb(35, 31, 32); font-family:symbol">k</span></span> and l and <span style="color:rgb(35, 31, 32); font-family:symbol; font-size:14px">k</span>/<span style="color:#231F20; font-family:symbol; font-size:12.0pt">l</span> ratio calculation is recommended for evaluation and management of plasma cell disorders. However, some analytical issues persist in their measurements, among which a too large long-term imprecision seems to be the main challenge. We evaluated the new Optilite system (The Binding Site) for sFLC determination by comparing its performance with specifications for bias, imprecision (as CV) and total error derived from biological variation of sFLC. We collected data during one year of routine use by employing three reagent lots. The system alignment was checked using the two-level (L and H) Optilite control material by comparing the obtained long-term experimental mean (n=233, both levels) with the manufacturer’s assigned values. The protocol for CV evaluation employed the liquid-frozen BioRad Liquichek Control and a frozen serum pool tested for 125 and 79 runs, respectively. Inaccuracy was evaluated by results of four UK-NEQAS exercises [system-specific (Optilite) consensus value as reference]. Average cumulative bias [1.1% (L) and -2.0% (H) for sFLC<span style="color:rgb(35, 31, 32); font-family:symbol; font-size:14px">k</span>; 5.4% (L) and 0.1% (H) for sFLC<span style="color:rgb(35, 31, 32); font-family:symbol; font-size:16px">l</span>, respectively] fulfilled the desirable goals. CVs for sFLC<span style="color:rgb(35, 31, 32); font-family:symbol; font-size:14px">k</span> (7.1% for Liquichek and 6.6% for the pool, respectively), sFLC<span style="color:rgb(35, 31, 32); font-family:symbol; font-size:16px">l</span> (7.8% for both Liquichek and the pool) and <span style="color:rgb(35, 31, 32); font-family:symbol; font-size:14px">k</span>/<span style="color:rgb(35, 31, 32); font-family:symbol; font-size:12pt">l </span>ratio (8.9% for Liquichek and 10.2% for the pool, respectively) failed however to reach minimum quality goals. In EQAS evaluation, all sFLC <span style="color:rgb(35, 31, 32); font-family:symbol; font-size:14px">k</span> and <span style="color:rgb(35, 31, 32); font-family:symbol; font-size:16px">l</span> and 3 out of 4 <span style="color:rgb(35, 31, 32); font-family:symbol; font-size:14px">k</span>/<span style="color:rgb(35, 31, 32); font-family:symbol; font-size:12pt">l</span> ratio results were within the allowable total error. In our experience, the Optilite system shows a good method alignment suitable for sFLC interpretation using fixed cut-offs. However, the assay reproducibility is probably not suitable for optimal long-term monitoring of individual patients.</p>
Biochimica Clinica ; 42(1) 32-38 Contributi scientifici - Scientific papers

Il laboratorio nella medicina della riproduzione
Laboratory and Reproductive Medicine
R. Tomaiuolo \| M. Panteghini \|

Biochimica Clinica ; 41(4) 292-293 Editoriale - Editorial

Ringraziamento

M. Panteghini \|

Biochimica Clinica ; 41(4) 291 -

Anemia acquisita da ospedalizzazione: il ruolo delle perdite di sangue a scopo diagnostico
Hospital-acquired anemia: the role of diagnostic blood loss
E. Aloisio \| S Pasqualetti \| A. Dolci \| M. Panteghini \|
<p>Hospital-acquired anemia (HAA) is defined by a reduction of blood hemoglobin concentrations in hospitalized patients, in absence of bleeding episodes occurring during the hospital stay. One of the most important causes of HAA is the considerable amount of blood drawn for diagnostic purposes, which mainly affects critical patients in the intensive care units. Although usually underestimated by healthcare providers, HAA can be a significant problem, because it may increase the necessity of allogenic transfusions, the morbidity and mortality rates and healthcare costs. Strategies to minimize diagnostic blood loss should be implemented by both clinical wards and laboratories within wider patient blood management programs, with the aim of improving patient clinical outcome. These should include using small-volume test tubes, reduction of sample waste, optimization of testing frequency, early removal of central catheters and healthcare professional education.</p>
Biochimica Clinica ; 41(3) 208-215 Rassegne - Reviews

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
G. Lippi \| M. Panteghini \| S. Bernardini \| L. Bonfanti \| P. Carraro \| I. Casagranda \| M. Cavazza \| F. Ceriotti \| M. Ciaccio \| D. Coen \| D. Giavarina \| F. Giostra \| C. Paolillo \| M. Plebani \| G. Ricci \| G. Cervellin \|
<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 “highly recommended”, 2 “recommended in specific conditions” and 3 identified “highly discouraged” tests. The results of the questionnaire are shown as mean (±SD) of individual responses, thus allowing to define a scale of priority comprised between “highly recommended” and “highly discouraged”. Overall, 24 tests were classified as “highly recommended”, whereas 6 were “highly discouraged”. The remaining 16 tests were classified as “somehow recommended” or “somehow discouraged”. 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
F. Ceriotti \| M. Panteghini \| E. Guerra \| R. Leoncini \| G. Cevenini \|
<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 >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 <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

Ricordo di Carlo Franzini
In memory of Carlo Franzini
M. Panteghini \|

Biochimica Clinica ; 41(2) 119 Editoriale - Editorial

Validazione per l’impiego clinico delle determinazioni di emoglobina ed ematocrito sull’emogasanalizzatore GEM Premier 4000
Validation of clinical use of hemoglobin and hematocrit measurements on GEM Premier 4000 blood gas analyzer
E. Aloisio \| A. Panzeri \| S. Birindelli \| A. Dolci \| M. Panteghini \|

Biochimica Clinica ; 41(2) 189-191 Lettere all'Editore - Letters to the Editor

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
F. Braga \| E. Frusciante \| I. Infusino \| E. Aloisio \| E. Guerra \| F. Ceriotti \| M. Panteghini \|
<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 (≤±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

Verifica dell’accuratezza di tre glucometri “point-of-care” per l’utilizzo in ambito ospedaliero
Verification of accuracy of 3 glucose point-of-care testing (POCT) devices for their use in a hospital setting
E. Aloisio \| E. Frusciante \| A. Dolci \| M. Panteghini \|
<p>Inaccuracy in glucose POCT can lead to inappropriate therapeutic decisions. In this study, we evaluated the performance of 3 POCT glucometers by comparing results to those by an automated system traceable to higher-order references. Thirty-one heparinized venous blood samples were collected and assayed in duplicate for whole blood glucose concentrations with Roche Accu-Check Compact Plus, Nova Biomedical NovaPro and OK Biotech OKmeterDirect glucometers. All systems were calibrated to report plasma-equivalent results. Samples were then centrifuged and plasma glucose immediately determined by the hexokinase assay on Abbott Architect c16000 platform. The traceability of Abbott assay was checked by comparison with the hexokinase reference procedure performed on 3 samples. POCT performance was evaluated according to Cinical and Laboratory Standards Institute (CLSI) POCT12-A3 criteria [max. 5% of results >±12 mg/dL (for reference results <100 mg/dL) or >±12.5% (for reference results ≥100 mg/dL)] and consensus error grid (CEG) analysis. The Architect assay was perfectly standardized (mean bias, 0.2%). Sample glucose concentrations ranged from 62 to 326 mg/dL, with hematocrit spanning from 0.27 to 0.58 L/L. Average CV on duplicates was 3.5% for Roche, 3.6% for Nova and 5.9% for OK Biotech. All meters gave more than 5% of results (Roche 19.4%, Nova 16.1% and OK Biotech 22.6%) outside the CLSI criteria. However, all results, except two borderline values for OK Biotech, were within the low-risk zone according to CEG. In conclusion, by using CLSI acceptability criteria, the evaluated glucometers were not accurate enough for clinical use in a hospital setting. CEG analysis suggests, however, that this inaccuracy would not have any significant impact on patients’ outcome.</p>
Biochimica Clinica ; 41(1) 079-084 Contributi scientifici - Scientific papers

La diagnostica ematologica nel laboratorio clinico tra evoluzione tecnologica, analisi morfologica e tecniche innovative
The laboratory in hematology diagnostics between new technologies, morphological analysis and innovation
A. Marini \| S. Buoro \| M. Panteghini \|

Biochimica Clinica ; 40(3) 177-179 Editoriale - Editorial

Valutazione dell’imprecisione dell’esame emocromocitometrico eseguito con analizzatore Sysmex XN-9000
Evaluation of imprecision of automated complete blood cell count performed on Sysmex XN-9000 platform
S. Birindelli \| A. Carnevale \| E. Aloisio \| D. Szoke \| M. Panteghini \|

Biochimica Clinica ; 40(3) 282-284 Lettere all'Editore - Letters to the Editor

Il futuro della Medicina di Laboratorio
The future of Laboratory Medicine
S. Ferraro \| M. Panteghini \|

Biochimica Clinica ; 40(2) 075-077 Editoriale - Editorial

Biochimica Clinica fra passato e futuro
Biochimica Clinica between past and future
M. Panteghini \|

Biochimica Clinica ; 40(1) 12 Editoriale - Editorial

Diminuzione del “turnaround time” intralaboratorio della troponina attraverso un processo di miglioramento organizzativo continuo
Decreasing troponin intralaboratory turnaround time through a process improvement study
I. Conti \| A. Carnevale \| S. Pasqualetti \| S. Birindelli \| D. Szőke \| A. Dolci \| M. Panteghini \|

Biochimica Clinica ; 40(1) 69-71 Lettere all'Editore - Letters to the Editor

Appropriatezza prescrittiva ed esami di laboratorio: benvenuta l’idea ma necessita gestirla in modo più “appropriato”
Laboratory test appropriateness: the idea is welcome, but we need to manage it in an "appropriate" way
M. Panteghini \|

Biochimica Clinica ; 39(6) 548-550 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. 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 \| E. Fiorio \| L. Crinò \| M. A. V. Willrich \| A. Modenese \| M. Berardi \| G. Nordera \| M. Girelli \| R. Tomaiuolo \| D. Giavarina \| R. Dittadi \| L. Pighi \| 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 \| 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. 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 \| E. Fiorio \| L. Crinò \| M. A. V. Willrich \| A. Modenese \| M. Berardi \| G. Nordera \| M. Girelli \| R. Tomaiuolo \| D. Giavarina \| R. Dittadi \| L. Pighi \| 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 \| L. Belloni \| A. D'Avolio \| T. Trenti \| A. Fortunato \| T. Trenti \|

Biochimica Clinica ; 39(6) 546-547 Editoriale - Editorial

La diagnostica di laboratorio della malattia renale cronica in Italia: armonizzare è d’obbligo
The laboratory role in chronic kidney disease (CKD) in Italy: need of harmonization
M.S. Graziani \| S. Secchiero \| A. Terreni \| A. Caldini \| M. Panteghini \|
<p>The diagnosis and classification of CKD are based on laboratory tests. Aim of this paper is to examine different aspects of the laboratory contribution to verify their harmonization at national level. We review relationships between laboratory and clinical organizations, the role of 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines, the quality of creatinine and urine albumin measurements, the status of estimated glomerular filtration rate (eGFR) reporting, the use of cystatin C and testing plans. Questionnaires examining different aspects of the CKD diagnostics were sent out and EQAS for creatinine and urine albumin measurements were carried out. For creatinine measurement, enzymatic assays show the best performance, while for urine albumin a bias still exists between different methods. The eGFR is routinely reported by 75% of surveyed laboratories, but only 15% of them use the equation derived by the CKDEpidemiology Collaboration (CKD-EPI) study. For urine albumin, the recommended first morning void sample is used by ~60% of laboratories, but the wrong terminology of “microalbuminuria” is still used by >40% of them. Cystatin C is offered by a minority of laboratories. In conclusion, even if an improvement can be observed during the recent years, efforts for a better alignment to international recommendations are needed. Often they just require cultural and organizational changes, without the availability of additional economic resources.</p>
Biochimica Clinica ; 39(6) 617-626 Opinioni - Opinions

Riferibilità metrologica come strumento per la standardizzazione delle misure in Medicina di Laboratorio
Metrological traceability as a tool to standardize measurements in Laboratory Medicine
F. Braga \| M. Panteghini \|
<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’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 ‘traceable’ reference intervals.</p>
Biochimica Clinica ; 39(6) 551-558 Rassegne - Reviews

Impiego dell’indice itterico come esame di primo livello per l’identificazione dei campioni con concentrazioni anormali di bilirubinemia
Suitability of icteric index (II) as front-line test for the identification of blood samples with abnormal total bilirubin (TB) concentrations
S. Pasqualetti \| D. Szőke \| M. Panteghini \|
<p>The use of II as a front-line test for the preliminary identification of blood samples with abnormal TB concentrations was recently proposed. However, laboratories should validate this approach on their own analyzers. In this study we validated the diagnostic accuracy of II on the Abbott Architect c16000 platform. TB concentrations (diazo-based colorimetric assay) and corresponding II values (derived from absorbance measurements of samples diluted with saline) in heparinised plasma and serum samples were collected for a 3- month period. Linear regression analysis (LRA) (II vs. TB) was performed for both samples. The diagnostic performance of II to discriminate between abnormal (>1.2 mg/dL) and physiological TB concentrations was evaluated using the ROC curve analysis. The optimal II cut-off was selected at a negative predictive value (NPV) >99% for detection of abnormal TB values. TB and relative II were obtained from 18,486 serum and 3700 plasma samples. LRA showed a strong correlation between II and TB (serum: <em>r</em><sup>2</sup>=0.951; plasma: <em>r</em><sup>2</sup>=0.941). ROC curve analysis gave the following areas under the curve: serum, 0.948 (CI: 0.945-0.951), and plasma, 0.922 (CI: 0.913-0.930), showing the high accuracy of II for detecting abnormal TB on both sample types. An II ≤0.8 reliably excluded abnormal (>1.2 mg/dL) TB concentrations (serum, prevalence 25.4%: sensitivity 99.6%, NPV 99.7%; plasma, prevalence 16.7%: sensitivity 98.6%, NPV 99.4%). In our laboratory the use of an II value 0.8 as front-line test should allow the accurate “zero-cost” detection of samples with normal TB concentrations avoiding TB measurement in ~35% of serum and <span style="font-family:symbol">~</span>40% of plasma samples.</p>
Biochimica Clinica ; 39(4) 270-274 Contributi scientifici - Scientific Papers

Armonizzazione in laboratorio: verso una visione globale
Harmonization in Laboratory Medicine: towards a global vision
M. Plebani \| M. Panteghini \|

Biochimica Clinica ; 39(1) 012-014 Editoriale - Editorial

Casi clinici: un approccio nuovo per Biochimica Clinica, uno strumento utile per i professionisti di laboratorio
Case reports: a new approach by Biochimica Clinica, a useful tool for laboratory professionals
D. Giavarina \| G. Merlini \| M.S. Graziani \| M. Panteghini \|

Biochimica Clinica ; 39(1) 015-016 Editoriale - Editorial

Inibizione della glicolisi e accuratezza preanalitica nella misura della glicemia: come gestire l’impatto sul paziente?
Glycolysis inhibition and reliable plasma glucose results: is the clinical impact carefully considered?
D. Szőke \| C. Valente \| S. Pasqualetti \| M. Panteghini \|

Biochimica Clinica ; 39(1) 076-077 Lettere all'Editore - Letters to the Editor

Caratteristiche biochimiche e funzionali della proteina 4 dell’epididimo umano (HE4)
Biochemical and functional characteristics of human epididymis protein 4 (HE4)
D. Schiumarini \| S. Ferraro \| M. Panteghini \|
<p>Serum carbohydrate antigen 125 (CA125) is the established biomarker for detecting ovarian cancer (OC) recurrence and monitoring therapeutic response. The recent evidence calls into question the better performance of serum HE4 to detect patients with OC. The replacement of CA125 with HE4 appears advisable, but more focus is needed on the biochemical characterization of the protein structure, which is an overriding prerequisite to overcome possible methodological limitations. By resorting to published literature, we sought to review the available information on the protein structure, activity, functions and tissue expression under physiologic and pathologic conditions. The gene encoding for HE4, WFDC2, is composed by six exons. Five HE4 isoforms have been identified and recognized to define specific patterns differently expressed in neoplasm and normal tissues. Under physiologic conditions, HE4 is reported as protease inhibitor playing a crucial role in sperm maturation. In pathophysiology, HE4 is likely involved in cancer progression and metastases. In particular, HE4 is overexpressed in serous and endometrioid OC. Further information on the HE4 expression pattern in cancer progression will likely improve the clinical performance of the marker.</p>
Biochimica Clinica ; 38(5) 368-373 Rassegne - Reviews

Determinazione della vitamina B12 nel siero: indicazioni per la richiesta e l’interpretazione dei risultati
Determination of vitamin B12 in serum: recommendations for test request and result interpretation
S. Ferraro \| A. Dolci \| R. Mozzi \| M. Panteghini \|
<p>The measurement of vitamin B<sub>12</sub> (B12) in serum has an overall poor capability to rule out subjects for B12 deficiency. Furthermore, trying to identify those subjects by resorting to one solely test threshold level (e.g., the lower reference limit) may mislead the clinical diagnosis. Clinical laboratories should therefore optimize the test interpretation by replacing in their report the standard reference interval with a categorization of risk for B12 deficiency. Accordingly, a B12 concentration <100 ng/L may indicate a probable B12 deficiency and the need for vitamin supplementation. A possible or unlikely deficiency may be associated with marker results, respectively, below and above 300 ng/L. Finally, in subjects with B12 concentrations >400 ng/L, the vitamin deficiency may be excluded. Hemodialysis patients and pregnant woman have emerged as a target for B12 testing, although cost-effectiveness evaluations are difficult to perform in absence of reliable literature data. Monitoring B12 concentrations in serum to evaluate the effectiveness of B12 supplementation is not clinically useful.</p>
Biochimica Clinica ; 38(4) 326-329 Documenti - Documents

Determinazione dell’omocisteina plasmatica: indicazioni per la richiesta
Determination of plasma homocysteine: recommendations for test requesting
D. Szőke \| A. Dolci \| U. Russo \| M. Panteghini \|
<p>High plasma homocysteine concentrations can be caused by various factors, including low blood concentrations of B-complex vitamins. Hyperhomocysteinemia is widely believed to be associated with an increased risk of atherosclerotic disease; recent emerging evidence made, however, doubtful its role as cardiovascular risk factor. The aim of this document was to examine the appropriateness of homocysteine requesting in our clinical setting. Clinical guidelines, meta-analyses and systematic reviews were used as source of high level evidence. During the last two decades, the role of hyperhomocysteinemia was examined in a number of clinical conditions; however, the analysis of available data made us clear that determination of plasma homocysteine has only limited clinical role. Test requesting results to be appropriate only in case of suspected homocystinuria (an inherited disorder of the metabolism of the amino acid methionine), in patients with previous venous or arterial thromboembolism and in patients with severe (>100 μmol/L) [and possibly moderate (>30 μmol/L)] hyperhomocysteinemia treated with B-complex vitamins. Determination of plasma homocysteine is not recommended as a primary prevention tool for cardiovascular disease in the general population.</p>
Biochimica Clinica ; 38(3) 234-237 Documenti - Documents

Malattie del sistema nervoso e laboratorio: molto più che un settore di nicchia
Neurological disease and laboratory: much more than a niche
D. Giavarina \| M. Panteghini \|

Biochimica Clinica ; 38(3) 172-174 Editoriale - Editorial

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

Cancer biomarkers 2013: appunti a margine del convegno satellite EuroMedLab
Cancer biomarkers 2013: notes about the EuroMedLab satellite meeting
S. Ferraro \| R. Mozzi \| M. Panteghini \|
<p>Like all other interventions and devices in health care, cancer biomarkers should undergo a careful validation process before they are introduced into clinical practice for diagnostic or prognostic purposes. Particularly, for those candidate diagnostic markers, validation implies the assessment of their diagnostic accuracy according to pre-specified and standardized criteria. For prognostic purposes, large, protocol-driven prospective studies should assure unbiased results on the effectiveness of the investigated biomarkers in predicting patient’s risk of a future outcome, in aiding individual treatment choice and in patient counselling. The improvement of the methodology of research should finally contribute evidence of high level and strength useful to recommend or not the appropriate application of specific biomarkers in different clinical settings (screening, primary/secondary care, treatment monitoring, follow-up). In this presentation, we summarized the major issues highlighted during the recent EuroMedLab satellite meeting held in Venice (IT) on May 2013, in which standardized processes from the evaluation of biomarkers’ diagnostic accuracy and prognostic value for guideline development were discussed. In addition, current efforts on the research of novel molecules and therapeutic targets (proteins, exosomes, circulating nucleic acids) candidate to clinical introduction were briefly reviewed.</p>
Biochimica Clinica ; 37(6) 479-492 Opinioni - Opinions

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
F. Braga \| M. Panteghini \|
<p>To be accurate and equivalent laboratory results should be traceable to higher-order references. Furthermore, their analytic quality should fulfil acceptable measurement uncertainty as defined to fit the intended clinical use. To this aim, IVD manufacturers should define a calibration hierarchy to assign traceable values to their system calibrators and to fulfil during this process uncertainty limits for calibrators that should represent a proportion of the uncertainty budget allowed for clinical laboratory results. It is important that end-users may know and verify how manufacturers have implemented the traceability of their calibrators and estimated the corresponding uncertainty. Currently, the full information about traceability and uncertainty of calibrator is not available as manufacturers only provide the name of higher-order reference material and/or procedure to which the assay calibration is traceable without any description of steps and their corresponding uncertainty of the implemented traceability chain. Important post-market tools for IVD traceability surveillance are related to the verification by clinical laboratories of the consistency of declared performance during daily operations performed in accordance with the manufacturer’s instructions and the organization of appropriately structured EQAS. The former activity should be accomplished by analyzing system control materials and confirming that current measurements are in the manufacturer’s established control range. With regard to EQAS, it is mandatory that target values to materials are assigned with reference procedures by an accredited reference laboratory, that materials are commutable and a clinically allowable inaccuracy for participant’s results is defined in order to prove the suitability of laboratory measurements in clinical setting.</p>
Biochimica Clinica ; 37(6) 470-478 Opinioni - Opinions

Catene leggere libere delle immunoglobuline nel siero: un marcatore a metà del guado
Immunoglobulin free light chains in serum: a midstream biomarker
A. Dolci \| M. Panteghini \|

Biochimica Clinica ; 37(5) 344-346 Editoriale - Editorial

Valutazione delle prestazioni del sistema analitico SPAPLUS per la misura delle catene leggere libere del siero
Evaluation of the performance of SPAPLUS system for the measurement of free light chains in serum
I. Infusino \| A. Dolci \| M. Panteghini \|
<p>Measurements of serum immunoglobulin <span style="font-family:symbol">k</span> and <span style="font-family:symbol">l</span> free light chains (FLC) and FLC ratio calculation are recommended for the evaluation of plasma cell disorders. In this study we evaluated the performance of SPAPLUS analyzer using Freelite<span style="font-size:x-small"><sup>TM</sup></span> reagents (both from The Binding Site) for FLC determination. Particularly, we compared the system performance with allowable goals for bias, imprecision and total error derived from biological variation of FLC. We evaluated the SPAPLUS FLC using data collected during a 10-month period of routine use, employing three different reagent lots. The two-level (N and H) SPAPLUS control material was used for bias estimate by comparing the obtained long-term experimental means (n=54, both levels) to the corresponding manufacturer’s assigned values. The protocol for CV evaluation employed the liquid-frozen Bio-Rad Liquichek unassayed chemistry control, measured in each performed run (n=48). Inaccuracy was checked by results from five UK-NEQAS exercises [system-specific (SPAPLUS) consensus value as reference]. Average cumulative bias was -1.5% (control N) and -1.4% (control H) for <span style="font-family:symbol">k</span> FLC, and +6.6% (N) and +6.3% (H) for <span style="font-family:symbol">l</span> FLC, respectively. Overall CV at physiological concentrations resulted in 10.6% for <span style="font-family:symbol">k</span> FLC, 8.0% for <span style="font-family:symbol">l</span> FLC and 9.9% for FLC ratio. On EQAS evaluation, all <span style="font-family:symbol">l</span> FLC, four <span style="font-family:symbol">k</span> FLC and three FLC ratio results were within the minimum allowable total error. Considering our previous experience with other analytical systems, the SPAPLUS solution undoubtedly represents a significant step forward. However, a further improvement in measurement imprecision is probably needed to fulfill the stringent analytical goals derived from FLC biological variation.</p>
Biochimica Clinica ; 37(5) 370-375 Contributi Scientifici - Scientific Papers

Variabilità biologica delle catene leggere libere delle immunoglobuline nel siero
Biologic variation of immunoglobulin free light chains in serum
F. Braga \| I. Infusino \| A. Dolci \| M. Panteghini \|
<p>The measurement of serum <span style="font-family:symbol">k</span> and <span style="font-family:symbol">l</span> free light 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 multiple myeloma and related plasma cell disorders. Given the lack of reliable data available in literature, in this study we assessed biologic variability components of FLCs and FLC ratio by an accurately designed protocol. We collected five blood specimens from each of 21 healthy volunteers (9 men and 12 women; age range, 23-54 years) on the same day, every two weeks for two months. Serum specimens were stored at -80 °C until analysis and analyzed in a single run in duplicate using a SPAPLuS immunoturbidimetric platform and Freelite reagents (The Binding Site). Data were analyzed by ANOVA. Serum <span style="font-family:symbol">l</span> FLC concentrations were significantly (P <0.01) higher in men. The inter-individual 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, 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 the use of population-based reference intervals could be inadequate for test interpretation. The reference change value was between 20% and 30% depending from the assay imprecision. Desirable analytical goals for imprecision (CV), bias and total error were <4.0%, ±4.1% and ±10.7% for <span style="font-family:symbol">k</span> FLC, <3.5%, ±7.1% and ±12.9% for <span style="font-family:symbol">l</span> FLC, and <2.3%, ±4.0% and ±7.7% for FLC ratio.</p>
Biochimica Clinica ; 37(5) 376-382 Contributi Scientifici - Scientific Papers

Il laboratorio nel cancro dell’ovaio: e pur si muove!
Laboratory and ovarian cancer: and yet it moves!
S. Ferraro \| M. Panteghini \|

Biochimica Clinica ; 37(3) 176-178 Editoriale - Editorial

Serum human epididymis protein 4 vs. carbohydrate antigen 125 for ovarian cancer diagnosis: a systematic review

S. Ferraro \| F. Braga \| M. Lanzoni \| P. Boracchi \| E.M. Biganzoli \| M. Panteghini \|
<p>Human epididymis protein 4 (HE4) measurements in serum have been proposed for improving the specificity of laboratory identification of ovarian cancer (OC). This study sought to critically revise the available literature on the comparison between the diagnostic accuracy of HE4 and carbohydrate antigen 125 (CA-125) to provide evidence of HE4 additional clinical value. Literature search was undertaken on electronic databases and references from retrieved articles, and articles analyzed according to predefined criteria. Meta-analyses for HE4 and CA-125 biomarkers with odds ratio (OR), diagnostic sensitivity, specificity, positive (LR+) and negative (LR–) likelihood ratios as effect sizes were performed. Sixteen articles were originally included in meta-analyses, but two for HE4 and one for CA-125 were eliminated as outliers. Furthermore, for HE4 a publication bias was detected. ORs for both HE4 (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, although in a heterogeneous set of studies (P <0.0001). By combining sensitivity and specificity, the overall LR+ and LR– 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: 0.23-0.31) for CA-125, respectively. HE4 measurement seems to be superior to CA-125 in terms of diagnostic performance for identification of OC in women with suspected gynecological disease. Due to the high prevalence of OC in post-menopausal women and the need of data focused on early tumor stages, more studies tailored on these specific subsets are needed.</p>
Biochimica Clinica ; 37(3) 179-189 Rassegne - Reviews

Un raro caso di mesotelioma multicistico del peritoneo associato ad aumento di CA 125 e CA 19.9 nel siero
A rare case of benign multicystic mesothelioma of the peritoneum associated to CA 125 and CA 19.9 elevations in serum
S. Ferraro \| R. Mozzi \| C. Villa \| M. Crespi \| M. Panteghini \|
<p>Markedly increased CA 125 and CA 19.9 concentrations in serum are considered specific enough to reliably identify malignant cancers (ovarian and gastrointestinal tumours, respectively), although a consistent body of literature has reported marker elevations in several benign conditions. Here we report the case of a woman in post-menopausal status, with a previous history of hysterectomy, presenting with a 12-cm pelvic mass at sonography and serum CA 125 and CA 19.9 concentrations >400 kU/L. One month after initial presentation, she underwent surgical evaluation for laparoscopy, repeating marker determinations. Concentrations of CA 125 and CA 19.9 were still elevated, but decreased if compared with the previous data (~200 kU/L). Magnetic resonance imaging characterized a multicystic mass in the mesentery, allowing to hypothesize a benign multicystic mesothelioma of the peritoneum (BMMP). The laparoscopy revealed multiple cysts, some of them resulting in colliquation, associated to ascites. Histological examination of biopsy specimens confirmed BMMP as composed of multiple, thin-walled, irregularly spaced cysts lined by flattened and cuboidal mesothelial cells. The cystic colliquation was though as the main cause for decrease in marker concentrations. To our knowledge, this is the first case of BMMP associated with significantly increased concentrations of CA 125 and CA 19.9 and their decrease before any surgical treatment.</p>
Biochimica Clinica ; 37(3) 241-245 Casi Clinici - Case Report

Determinazione dell’epcidina: ma cosa stiamo “misurando”?
Quantification of hepcidin: what are we measuring?
I. Infusino \| A. Dolci \| M. Panteghini \|

Biochimica Clinica ; 37(2) 135-137 Lettere all'Editore - Letters to the Editor

Rilevazione, monitoraggio e trattamento di non conformità nella fase preanalitica: l’esperienza di un ospedale universitario metropolitano
Recording, monitoring, and managing pre-analytical issues in a metropolitan university hospital
R. Mozzi \| A. Carnevale \| C. Valente \| A. Dolci \| M. Panteghini \|
<p>Errors in laboratory testing process may have an adverse impact on patient care. The pre-analytical phase is responsible for ~70% of these errors. In this study we present our experience in assessing the frequency of pre-analytical errors in our university hospital, by monitoring their trend over time and comparing data with goals suggested in literature. The impact of corrective actions, if any, was also checked. A comprehensive retrospective analysis of pre-analytical nonconformities (NC) recorded through laboratory information system over a 5-year (2007-2011) time span was undertaken. Retrieved data were evaluated on a yearly basis, first for NC type and then for type of sample, laboratory section and hospital department involved. The relatively most frequent NC was the test request without the corresponding sample, accounting on average for 2.3% of all requested tests. Hemolysis occurred for in average 1.15% of all requested tests, affecting ~20,000 determinations per year, mostly interesting clinical wards taking care of critical patients, i.e. neonatology, oncology, and emergency department. Clotted and not sufficient samples showed a significant reduction over time after changing the analytical system measuring erythrocyte sedimentation rate and adopting more reliable tubes, easier to fill in and mix up. NC related to samples conveyed at wrong temperature were also relatively frequent. Our results show that recording, monitoring, and critically evaluating pre-analytical issues in laboratory testing process is mandatory for providing a good laboratory service, permitting to identify causes of NC and to apply corrective interventions that may help to reduce their incidence.</p>
Biochimica Clinica ; 37(2) 095-099 Contributi scientifici - Scientific Papers

Standardizzazione della misura e traguardi analitici per l’emoglobina glicata
Measurement standardization and analytical goals for glycated hemoglobin
F. Braga \| M. Panteghini \|
<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

Un ulteriore passo verso una migliore efficienza ed efficacia della determinazione della calprotectina fecale
A further step to improve the cost-effectiveness of calprotectin determination
S. Ferraro \| R. Mozzi \| M. Panteghini \|

Biochimica Clinica ; 37(2) 133-134 Lettere all'Editore - Letters to the Editor

Accuratezza nella misura e impiego clinico dell’esame di laboratorio: l’esempio dell’albumina sierica
Measurement accuracy and clinical use of laboratory tests: the case of serum albumin
I. Infusino \| M. Panteghini \|
<p>Albumin is the major plasma protein and its determination is used for the prognostic assessment of several diseases. Clinical guidelines call for monitoring of serum albumin with specific target cut-offs that are independent of the assay used. This requires accurate and equivalent results among different commercially available methods (i.e., result standardization) through a consistent definition and application of a reference measurement system. This should be associated with the definition of measurement uncertainty goals based on medical relevance of serum albumin to make results reliable for patient management. In this paper, we show that, in the current situation, if one applies the analytical goals for serum albumin measurement derived from its biologic variation, the uncertainty budget derived from each step of the albumin traceability chain is probably too high to fulfil the established quality levels for albumin measurement and to guarantee the accuracy needed for clinical usefulness of the test. The situation is further worsened if non-specific colorimetric methods are used for albumin measurement as they represent an additional random source of uncertainty.</p>
Biochimica Clinica ; 37(1) 48-52 Opinioni - Opinions

Etica e metodologia di scrittura di un lavoro scientifico
Publication ethics and scientific writing
F. Braga \| M.S. Graziani \| M. Panteghini \|
<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’ 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’ responsibility includes conflict of interest and confidentiality. Among the journal editor’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 “Title”, how to prepare a comprehensive “Abstract”, how to cope with the “Introduction”, how to improve the description of employed “Methods”, how to present data in the “Results” section, and how to better organize the results “Discussion”. 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

Procalcitonina: tra evidenze e criticità
Procalcitonin: between evidence and critical issues
M. Panteghini \|

Biochimica Clinica ; 37(1) 12-14 Editoriale - Editorial

Frequenza e significato clinico di valori di antigene carboidratico (CA) 19.9 marcatamente elevati in una popolazione di pazienti ospedalizzati
Prevalence and clinical significance of enormously increased carbohydrate antigen (CA) 19.9 concentrations in hospitalised patients
R. Mozzi \| S. Ferraro \| C. Valente \| M. Panteghini \|
<p style="text-align: justify;">Markedly elevated CA 19.9 concentrations in serum are regarded as specific enough to reliably identify pancreatic cancer, even if a consistent body of literature shows CA 19.9 concentrations >1000 kU/L in a variety of benign conditions. Scarce data are, however, available on the prevalence and clinical significance of CA 19.9 values >10,000 kU/L. Here we present a case series of 18 consecutive patients admitted to our hospital in a time period of 14 months showing an enormous elevation of CA19.9 concentrations (11,568 to >100,000 kU/L), with the aim to assess the association of such concentrations with the presence of pancreatic cancer and, more in general, with tumours of the gastrointestinal system. We also tried to define whether the exact measurement of CA 19.9 concentrations in this range, which needs serial sample dilutions, is cost-effective. CA 19.9 measurements, including sample dilutions according to a defined laboratory protocol, were performed on Roche Modular EVO system. The yearly prevalence of hospitalized patients tested for CA 19.9 and with marker concentrations >10,000 kU/L was 2.9%. All recruited patients were diagnosed as malignancies: 15 had primary or secondary pancreatic cancer, two had gastric cancer, and one a cholangiocarcinoma. CA 19.9 concentrations ranged between >10,000-30,000 kU/L in 9 cases, >30,000-60,000 kU/L in two, >60,000-100,000 kU/L in three, and >100,000 kU/L in four cases, respectively. A surgical resection of the tumour was performed in five patients, independently of CA 19.9 concentrations. The median patient’s survival was <6 months. In conclusion, CA 19.9 concentrations >10,000 kU/L unequivocally identify a gastrointestinal malignancy, more frequently (~83%) a primary or secondary pancreatic cancer. Exactly measuring CA 19.9 concentrations >10,000 kU/L after multiple sample dilution does not add relevant information for patients’ prognosis and treatment.</p>
Biochimica Clinica ; 36(6) 436-440 Casi Clinici - Case Report

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
A. Carobene \| F. Ceriotti \| I. Infusino \| E. Frusciante \| M. Panteghini \|
<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;"></span>2.00 mg/dL, with 2011 results – except for one method group – well inside the desirable bias (<span style="font-family: symbol;"></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;"></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

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 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

Teoria e pratica degli intervalli di riferimento riferibili
Theory and practice of traceable reference intervals
F. Ceriotti \| I. Infusino \| M. Panteghini \|
<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

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

Standardisation of cardiac troponin I measurements - the way forward
Standardisation of cardiac troponin I measurements - the way forward
J. Tate \| M. Panteghini \|
<p><strong>Cardiac troponin I (cTnI) assays produce different results.</strong> To achieve closer comparability of cTnI values among assays, the use of a suitable reference material is proposed for use to calibrate commercial assays. To assign true cTnI concentrations to this material, establishment of a reference procedure for cTnI is also required.</p>
Biochimica Clinica ; 35(6) 461-464 OPINIONI - OPINIONI

Biomarcatori del carcinoma della prostata: la caccia è sempre aperta
Biomarkers for prostate cancer: the hunt is still open
A. Dolci \| MT. Sandri \| M. Panteghini \|

Biochimica Clinica ; 35(5) 353 EDITORIALE - EDITORIALE

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
I. Infusino \| F. Braga \| R. Paleari \| A. Mosca \| M. Panteghini \|

Biochimica Clinica ; 35(5) 377 OPINIONI - OPINIONI

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
F. Braga \| A. Dolci \| C. Valente \| A. Boido \| A. Moretti \| S. Guzzetti \| M. Panteghini \|

Biochimica Clinica ; 35(4) 301 CONTRIBUTI SCIENTIFICI - CONTRIBUTI SCIENTIFICI

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).
F. Braga \| A. Dolci \| A. Cavallero \| A. GhezzI \| I. Infusino \| M. Milano \| M. Rubino \| M. Panteghini \|

Biochimica Clinica ; 35(3) 186 CONTRIBUTI SCIENTIFICI - CONTRIBUTI SCIENTIFICI

Editoriale
Editorial
M. Panteghini \|

Biochimica Clinica ; 35(1) 9 EDITORIALE - EDITORIALE

Stima dell'incertezza della misura della concentrazione di attività catalitica dell'alanina amminotransferasi (ALT) nel siero mediante il metodo di riferimento IFCC
Calculation of uncertainty of measurement of the catalytic activity concentration of alanine amminotransferase (ALT) in serum by the IFCC reference procedure.
E. Frusciante \| I. Infusino \| M. Panteghini \|

Biochimica Clinica ; 35(1) 20 CONTRIBUTI SCIENTIFICI - CONTRIBUTI SCIENTIFICI

2009 Annual Report of the IFCC Scientific Division (SD)
2009 Annual Report of the IFCC Scientific Division (SD)
M. Panteghini \|

Biochimica Clinica ; 34(2) 153 NOTIZIE SIBioC - NOTIZIE SIBioC

Standardizzazione in enzimologia clinica: una sfida per la teoria della riferibilità metrologica
Standardization in clinical enzymology: a challenge for the theory of metrological traceability
I. Infusino \| F. Ceriotti \| M. Panteghini \|

Biochimica Clinica ; 34(2) 96 RASSEGNE - RASSEGNE

Un nuovo referto per l'emoglobina glicata: il futuro è qui
A new report for HbA1c: the future is here
M. Panteghini \|

Biochimica Clinica ; 34(2) 93 EDITORIALE - EDITORIALE

Laboratory evaluation of pancreatic diseases
Laboratory evaluation of pancreatic diseases
M. Panteghini \|

Biochimica Clinica ; 34(1) 19 RASSEGNE - RASSEGNE