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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

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

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Via L. Temolo 4, 20126 Milano

Responsible Editor
Giuseppe Agosta

Editorial Secretary
Andrea di Bello
Biomedia srl
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ISSN print: 0393 – 0564
ISSN digital: 0392- 7091

Biochimica Clinica: VOL.43 N.1

Scarica intero fascicolo
L’avanzamento della biologia molecolare clinica nella diagnostica dilaboratorio richiede importanti attività di armonizzazione
Biochimica Clinica 2019; 43(1) 011-012
DOI: 10.19186/BC_2019.007
Pubblicato online il: 19.02.2019
Editoriale - Editorial
Nota all'Editoriale sul Documento della Organizzazione Mondiale della Sanità
Biochimica Clinica 2019; 43(1) 013
Pubblicato online il: 19.02.2019
Editoriale - Editorial
Il ruolo della metabolomica nella diagnosi e nel monitoraggio delle malattie metaboliche ereditarie
Metabolomics: a challenge for detecting and monitoring inborn errors of metabolism.
M. Mussap  |  M. Zaffanello  |  V. Fanos  | 

Timely newborn screening and genetic profile are crucial in early recognition and treatment of inborn errors of metabolism (IEMs). A proposed nosology of IEMs has inserted 1015 well-characterized IEMs causing alterations in specific metabolic pathways. With the increasing expansion of metabolomics in the clinical biochemistry and laboratory medicine communities, several research groups have focused their interest the analysis of metabolites and their interconnections in IEMs. Metabolomics has the property to extend metabolic information leading to achieve an accurate diagnosis for an individual patient and to discover novel IEMs. Structural and functional information on 247 metabolites associated with 147 IEMs and 202 metabolic pathways involved in various IEMs have been reported in the human metabolome data base (HMDB). For each metabolic gene, a new computational approach can be developed for predicting a set of metabolites that are expected to change their concentration in urine, blood and other biological fluids after gene knockout. Both the targeted and the untargeted mass spectrometry (MS)-based metabolomic approaches have been used to expand the range of disease-associate metabolites. The quantitative targeted approach, in conjunction with chemometrics, can be considered a basic tool for validating known diagnostic biomarkers in various metabolic disorders. The untargeted approach increases the identification of new biomarkers in known IEMs and allows pathways analysis. Urine is an ideal biological fluid for metabolomics in neonatology; however, the lack of standardization of the preanalytical phase may originate potential interferences in metabolomic studies. Integrating genomic with metabolomic data represents the current challenge for improving diagnosis and prognosis of IEMs. The goals consist of the identification of both metabolically active loci and genes relevant to a disease phenotype, that means deriving disease-specific biological insights.

TAG: errori congeniti del metabolismo (ECM)   malattie metaboliche ereditarie   programmi nazionali di screening del neonato.  
Biochimica Clinica 2019; 43(1) 014-023
DOI: 10.19186/BC_2019.002
Pubblicato online il: 22.01.2019
Rassegne - Reviews
La biologia molecolare clinica nella valutazione e prevenzione del rischio cardiologico nell’attività sportiva e nell’attività motoria intensa
Clinical molecular biology in the assessment and prevention of cardiological risk in case of participation in sports activity and intense physical activity

We review the clinical molecular biology approach for the prevention of cardiological diseases, essentially via risk assessment at personal level by DNA analysis. Intense physical activity, particularly during athletic performances, can result in syncope or even cardiac arrest, often followed by sudden
cardiac death. An approach to the prevention of such tragic events is predictive medicine (presence of pathogenic mutations in cardiac genes), besides the conventional tools used in cardiology (mainly electro and echocardiogram under stress conditions). Accordingly, we list the major cardiac diseases and their related genes and derivative proteins which are instrumental for normal heart function. Alterations can occur in ion channel genes, in genes
encoding desmosomial and junctional proteins, sarcomeric and Z-disc proteins, proteins for the cytoskeleton at the nuclear envelope, and in genes encoding mitochondrial proteins. Thus, we constructed two sets of gene panels: one set to discriminate among confounding heart diseases, and another set based on a cost-benefit criterion according to the most or less frequent genes bearing pathogenic variants that entail a higher or lower predisposing risk. This
approach should be used to monitor pre-participation athletes and also amateurs who belong to families in which at least 1-2 subjects are affected by cardiac alterations. The risk should be identified with the aim to monitor subjects in order to prevent cardiac arrest and even sudden cardiac death.

TAG: Prestazione atletica   valutazione del rischio   proteine mitocondriali  
Biochimica Clinica 2019; 43(1) 024-043
DOI: 10.19186/BC_2019.006
Pubblicato online il: 04.02.2019
Rassegne - Review
La riorganizzazione del settore dedicato alla diagnostica proteica: un esempio virtuoso fondato su criteri di Evidence Based Laboratory Medicine e di sostenibilità economica
The organization of the protein unit: a beneficial example founded on evidence based laboratory medicine criteria and on the appropriate use of the available resources
P. Natali  |  T. Trenti  | 

The sustainability of the National Health Service is a current subject of debate  due to the pressure that the changes in our societies are having on health systems. Reviewing diagnostic processes is increasingly urgent to contain costs and to maintain the quality of the health services provided.The Evidence Based Laboratory Medicine (EBLM) approach allows to identify and eliminate obsolete methods, replacing them with more adequate ones. The EBLM approach can also provide higher diagnostic accuracy, a rationalisation of diagnostic pathways, a reduction of turnaround-time and a decrease of costs. To reach these objectives, a careful analysis of production processes and assessment of the costs are both necessary. The EBLM approach has been applied to the Protein Unit of Laboratory of Modena. The change in the workflow of the Bence Jones protein determination and the consolidation of the measurement of a number of serum proteins on clinical chemistry analysers allowed a better diagnostic accuracy coupled to important economical savings. The savings made it possible to extend the availability of the free light chains measurements (that before was restricted to patients admitted to the haematology department) to the out-patients of the Province of Modena. The EBLM approach is the most effective way to reach such objectives: really, providing better quality performance does not necessarily correspond to an increase of costs. In addition to developing an adequate level of scientific expertise, the laboratory professional must acquire managerial skills to introduce up-to-date diagnostic methods and to optimize the use of assigned resources, in all areas of laboratory medicine.


TAG: Ematologia   proteine   flusso di lavoro   diagnostica di laboratorio  
Biochimica Clinica 2019; 43(1) 044-051
DOI: 10.19186/BC_2018.065
Pubblicato online il: 31.10.2018
Contributi Scientifici - Scientific Paper
Disegno e sviluppo di una applicazione per dispositivi mobili per migliorare l’appropriatezza prescrittiva degli esami di laboratorio del medico di medicina generale: focus sull’ipertensione arteriosa
An application for mobile devices to improve the appropriateness of laboratory test request by general practitioners: focus on blood hypertension

The prevalence of consultations of general practitioners (GPs) is huge, and for an unknown number of patients a consistent amount of diagnostic laboratory tests is requested. One of the tasks of GPs is to identify patients in need of specific laboratory tests, to improve the patient outcomes taking at the same time into consideration the risk of over-diagnosis and treatment and the available resources as well. To support GPs in their decisional process, we developed a dedicated software application (APP) for mobile devices; the APP contents were developed in collaboration with GPs, with students of a GP training course and with laboratory medicine specialists. We identified the laboratory tests useful for the management of the most frequent diseases observed in GPs' offices,  that are supported by the best available evidence. The first attempt was made considering blood hypertension. Aim of the paper is the description of the process of the APP development,  that  includes data available from national and international guidelines. This promising tool could help GPs to prescribe suitable laboratory tests in different clinical scenario (diagnosis, evaluation of therapy, monitoring) and to promote the implementation of the evidence-based practice of laboratory medicine, reducing the requests of inappropriate tests and accurately identifying patients who need a second level referral (nephrologist, endocrinologist).

TAG: General Practitioners   Hypertension   Diagnostic tests  
Biochimica Clinica 2019; 43(1) 052-058
DOI: 10.19186/BC_2018.068
Pubblicato online il: 26.11.2018
Contributi Scientifici - Scientific Paper
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

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-β 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’s study received a BIVAC grade C, EuBIVAS a grade A. EuBIVAS is a large scale study, with 1609 and 1728 results for NSE and S100-β, respectively. In Johnson’s study, only 40 results were available. The EuBIVAS CVI estimates [NSE, 10.9% (10.3-11.5); S100-β , 10.2% (9.6-10.7)] were clearly lower than Johnson’s CVIs [NSE, 22.1% (9.9-34.3); S100-β, 18.9% (8.5-29.4)]. The overlapping CI between the two estimates are caused by Johnson’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.


TAG: variabilità biologica   enolasi neurone-specifica   proteina S100-β  
Biochimica Clinica 2019; 43(1) 059-066
DOI: 10.19186/BC_2019.001
Pubblicato online il: 14.01.2019
Contributi Scientifici - Scientific Paper
La catena di custodia: problematiche generali ed esperienza nella Azienda Sanitaria Locale Napoli 1 Centro
The chain of custody: general issues and the experience of the Azienda Sanitaria Locale of Naples (Italy)

The toxicology laboratories were created at the end of 1996 within the city area of Naples (Italy) and, so far, have gained an important experience. Their tasks are to monitor drug abuse, the use of metadone and buprenorphine and the diagnosis and monitoring of alcoholism through the screening of urine and serum samples. From this long-lasting experience, we realized that one of the main critical concern of this activity is the implementation and the maintenance of the custody chain, that is especially needed in the presence of forensic issues. The aim of this paper is to analyze the Italian national and regional laws and administrative indications on this topic. We dedicated a particular interest to the rules established by the Regione Campania, where the laboratory is situated. After considering that a high percentage of samples non-conformities were due to the lack of a proper chain of custody (i.e. 66.7%), we adopted a specific procedure based on the use of a dedicated kit containing both the tubes for a safe sample collection and the related documents. A large amount of time was dedicated to illustrate and diffuse the procedure to the nurses and the other personnel working mainly in the First Aid centers of the Azienda Sanitaria Locale of Naples. The collected data show that the percentage of the unsuitable samples decreased to 38% at the end of the year 2017 when the information and training courses succeeded in involving all the dedicated personnel. We plan to revise periodically the procedures and reinforce the message to further optimize the results

TAG: Metadone   buprenorfina   alcolismo   droghe di abuso  
Biochimica Clinica 2019; 43(1) 067-075
DOI: 10.19186/BC_2018.067
Pubblicato online il: 15.11.2018
Opinioni - Opinions
Il Grading of Recommendations Assessment Development and Evaluation(GRADE) quale metodologia sistematica e trasparente per valutare l’esame di laboratorio nella formulazione di raccomandazioni e linee guida
The Grading of Recommendations Assessment Development and Evaluation (GRADE) methodology assystematic and transparent framework to evaluate diagnostic test value in supporting guide lines andrecommendations issuing.

A multidimensional pathway based on GRADE Evidence to Decision (EtD) frameworkis presented. The aim of the document is to define a valid process to assess the adoption of a diagnostic test and theconsequences of the decision. The framework includes three sections reflecting the main steps of GRADE EtD:formulating the relevant question, making an assessment of the evidence, and drawing conclusions. As a matter ofexample, the EtD framework is used to present the evidence concerning the molecular diagnosis of sepsis inneonates including seven dimensions: (1) formulating the question; (2) assessment of diagnostic test accuracy; (3)certainty of the evidence; (4) effects of test on the main patient outcome; (5) balance between the desirable andundesirable effects; (6) resource use; (7) equity, acceptability and feasibility. The example is used to better elucidatethe concepts and to show how reviewers may complete each dimension with the relevant information avaiable.Several factors could influence the final decisions: the relevance of the problem, the values of diagnostic accuracy,the effects of the test on main patient outcome; other issues may play a role. The framework consists of acomprehensive decision aid model to ensure that all important criteria are considered to explain a judgment. Thisapproach could help health professionals to use the best available research evidence in a structured and transparentway to inform decisions in the context of laboratory medicine.

TAG: framework   EBML   sepsis  
Biochimica Clinica 2019; 43(1) 076-089
DOI: 10.19186/BC_2019.004
Pubblicato online il: 04.02.2019
Documenti - Documents
Glossario di biologia molecolare e biologia molecolare clinica. Parte I: termini generali
Glossary of molecular biology and clinical molecular biology. Part I: general terms.

This glossary has beenconceived to help readers, who are less experienced with molecular biology, to approach this field of laboratorymedicine, which is gaining increasing importance in the analytical and diagnostic processes. The glossary isorganized into two separate sections: general terms of molecular biology and clinical molecular biology (molecularbiology techniques, and molecular diagnostic testing). For some of the terms, a link to articles published in BiochimicaClinica, where these terms are employed is included. For each term the corresponding English version is reported;in addition, all the entries of the glossary are listed in the Appendix both in Italian and in English alphabetical order.

TAG: Biologia molecolare   biologia molecolare clinica   termini generali  
Biochimica Clinica 2019; 43(1) 090-105
DOI: 10.19186/BC_2019.008
Pubblicato online il: 19.02.2019
Documenti - Documents
Raccomandazioni per l’esecuzione di indagini molecolari su biopsia liquida in oncologia
Reccomendations for using of molecular assays on liquid biopsy: the first document provided by intersociety Group AIOM, SIF, SIAPEC-IAP, SIBioC.

Liquid biopsy in cancer patients is mainly based on the analysis of circulating tumor DNA (ctDNA) enriched from biological fluids. This approach has more recently been proposed for the detection of oncogenic alterations in blood, cerebrospinal fluid (CSF), or urine through the use of sensitive technologies, mainly digital PCR (ddPCR) and massive parallel sequencing (MPS). Liquid biopsies have the advantage of overcoming some of the drawbacks associated with tumor biopsies, being blood samples easy to obtain from patients. Plasma ctDNA may better represent the total landscape of oncogenic alterations found across all tumor sites. Several commercially available liquid biopsy platforms based on MPS technology are currently analytically validated, with sensitivities, specificities, false negative rates, false positive rates, positive predictive values, and negative predictive values evaluated in comparison with tissue. The specificity of ctDNA is generally high while the sensitivity varies between different platforms. However, these data have not yet led to the incorporation of ctDNA into
routine clinical practice. The present Reccomandation represents a synthesis of the main evidences supporting use of liquid biopsy based assays in clinical setting. This inter-society approved document was prepared by a panel of expert belonging to four scientific societies who tried to provide the main useful information for the implementation of liquid biopsy-based test in clinical and laboratory practice.

TAG: Oncogene   cancerogenesi   società scientifica   DNA del tumore circolante  
Biochimica Clinica 2019; 43(1) 106-114
DOI: 10.19186/BC_2019.005
Pubblicato online il: 04.02.2019
Documenti SIBioC - SIBioC Documents
In ricordo di Jillian (Jill) Tate
In memory of Jillian (Jill) Tate
Biochimica Clinica 2019; 43(1) 115-117
Pubblicato online il: 28.02.2019
Notizia SiBioC - News SIBioC
Un caso di linfoadenopatia, epatosplenomegalia e triptasi elevata
A case of lymphadenopathy, hepatosplenomegaly and elevated serum tryptase level

A case of lymphadenopathy, hepatosplenomegaly and elevated serum tryptase level. Mastocytosis is a rare clonal disease characterized by neoplastic proliferation of mast cells in one or more organs, frequently skin and bone marrow. Diagnosis and classification of mastocytosis is based on the identification of neoplastic mast cells in according to the morphological, immunophenotypical and/or molecular criteria established by the WHO. For the diagnosis, serum levels of the tryptase which correlate with quantity and activity of mast cells is particulary useful. This case reports about a 60-year-old man with hepatosplenomegaly, modest monoclonal component, reactive lymph node hyperplasia and moderate macrocytic anemia (haemoglobin:129 gr/L). Bone marrow aspiration shows areas of infiltration of atypical mast cells type II and rarely type I with aberrant immunophenotype: CD45++CD117++CD2+CD25+. The tryptase concentration is significantly increased. According to WHO 2008 criteria, diagnosis of systemic mastocytosis is made. Early diagnosis of mastocytosis is pivotal because immunotherapy is often required to reduce the risk of allergic reactions or major bone complications.

TAG: Mastocitosi   Triptasi   Immunoterapia  
Biochimica Clinica 2019; 43(1) e1-e3
DOI: 10.19186/BC_2018.051
Pubblicato online il: 06.09.2018
Casi Clinici - Clinic Case
Valutazione della risposta alla terapia in un paziente con amiloidosi AL e basse concentrazioni della catena leggera libera monoclonale
Evaluation of response to treatment in a patient with light chain amyloidosis and low free light chain burden

Evaluation of response to treatment in a patient with light chain amyloidosis and low free light chain burden. In patients with light chain (AL) amyloidosis, reduction of amyloidogenic circulating free light chain (FLC) concentration translates in improvement of organ dysfunction and is associated with an increase in overall survival. Validated criteria for hematologic response to therapy are based on FLC quantification. However, patients with a difference between involved and uninvolved FLC (dFLC) <50 mg/L are not evaluable for hematologic response. Here we report the case of a 69 year old man with AL (λ) amyloidosis with renal involvement, presenting a low-FLC burden (dFLC 41 mg/L) at diagnosis. After two lines of treatment, a profound reduction of amyloidogenic FLC (dFLC 0 mg/L) was associated with an improvement of organ dysfunction. This case emphasizes the role of FLC assessment in the monitoring also of patients with a low-dFLC burden.


TAG: immunoglobuline   disfunzione d'organo   sindrome nefrosica  
Biochimica Clinica 2019; 43(1) e4-e6
DOI: 10.19186/BC_2018.047
Pubblicato online il: 01.08.2018
Casi Clinici - Case Report
Caso di emofilia A acquisita in paziente con sanguinamento endooculare
Intraocular hemorrhage in a patient with acquired hemophilia A

Intraocular hemorrhage in a patient with acquired hemophilia A. Intraocular hemorrhage is frequently encountered by ophthalmologists and by emergency room professionals as well. Although the diagnosis of intraocular hemorrhage is  easy  by fundoscopic examination or ultrasonography, further investigation may be required to determine the underlying etiology. In the literature, several cases of intravascular bleeding caused by the use of warfarin and new oral anticoagulants (NOACs) are described. We report here  a case of intraocular hemorrhage in a patient with acquired hemophilia A (AHA).

TAG: Emorragia oculare   anticoagulanti   carenza fattore VIII   warfarin  
Biochimica Clinica 2019; 43(1) e7-e8
DOI: 10.19186/BC_2018.049
Pubblicato online il: 25.05.2018
Casi Clinici - Case Report