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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

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
Andrea di Bello
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



Biochimica Clinica: VOL.45 N.1

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Diagnosi biochimica precoce di preeclampsia: un traguardo possibile?
TAG: diagnosi   biochimica   preeclampsia  
Biochimica Clinica 2021; 45(1) 011-012
DOI: 10.19186/BC_2021.006
Published online: 10.02.2021
Editoriale - Editorial
 
I Big Data e la Medicina di Laboratorio
M. Vidali  | 
TAG: big data   medicina di laboratorio   tecnologie  
Biochimica Clinica 2021; 45(1) 013-014
DOI: 10.19186/BC_2021.007
Published online: 10.02.2021
Editoriale - Editorial
 
Il ruolo del laboratorio clinico nella diagnosi precoce di preeclampsia
The role of the clinical laboratory in the early diagnosis of preeclampsia
M. Montagnana  |  A. Tagetti  |  C. Fava  | 
<p>Hypertensive pregnancy disorders include a large spectrum of conditions, including pre-existing chronic hypertension, gestational hypertension, preeclampsia (PE) and eclampsia. In particular, PE is one of the most important causes of maternal morbidity and mortality and perinatal death, preterm birth, and delayed intrauterine growth. The studies support a pathogenetic model of insufficient placentation which results in a vicious circle clinically dominated by an increase in blood pressure and proteinuria in the first phase, and by the involvement of the central nervous system up to convulsions in the more advanced stages. A crucial aspect of patient management is therefore represented by the identification of biological markers measurable in maternal blood (circulating) useful in the diagnosis, prognostic stratification and monitoring. In particular, in recent years many resources have been used to identify a biophysical and biochemical screening test aimed at identifying women at greater risk of PE, but none of these tools when used alone has demonstrated a significant predictive value. Few biomarkers are currently used in clinical practice. The analysis of the literature suggests that angiogenic and anti-angiogenic molecules, in particular the fms-like-tyrosine-kinase receptor 1 and placental growth factor (sFlt-1/PlGF) ratio, can be considered the biomarkers with the best diagnostic performance in the second trimester of pregnancy. However, doubts remain about their use in clinical practice before the 20th gestational week.</p>
TAG: ipertensione   preeclampsia   biomarcatori  
Biochimica Clinica 2021; 45(1) 015-025
DOI: 10.19186/BC_2020.093
Published online: 14.01.2021
Rassegne -
 
I micro-RNA quali potenziali biomarcatori per la diagnosi e la prognosi del cancro del pancreas: scelte metodologiche e criticità
Micro-RNAs as potential diagnostic and prognostic biomarkers in pancreatic cancer: methodological choices and issues
<p>Pancreatic cancer is the fourth cause of the death by cancer worldwide. It remains the only cancer whose survival has not improved in the last 40 years (only 18% of patients are still alive after 1 year, and 5% after 5 years), because of the high metastatic capacity and chemoresistance of the tumour. Complete tumour resection offers a chance to improve prognosis, but only 20% of patients are suitable for surgery. Although carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) are commonly used biomarkers in clinical practice, they are not sufficiently sensitive and specific for early diagnosis neither for predicting response to treatment. The search for biomarkers for early diagnosis, post-operative surveillance and prognosis prediction is therefore fundamental in the context of pancreatic cancer.<br />Circulating micro-RNAs (miRNAs), emerging regulators of gene expression, have been reported by several studies as powerful non-invasive biomarkers in the pancreatic cancer setting, because of their presence and stability in human body fluids. Distinctive miRNAs expression profiles have been associated to pancreatic cancer; furthermore, changes in their expression seems to identify cancer development and response to treatment. Although many papers have been published in this field, the results are still controversial and no consensus has reached about sample type, methodologies and protocols to be adopted thus hampering their introduction into routine practice. This paper aims to summarize the methodological choices in the analysis of circulating miRNAs with particular focus on the critical points of the different phases of the process.</p>
TAG: miro-RNA   biomarcatori   pancreas  
Biochimica Clinica 2021; 45(1) 026-034
DOI: 10.19186/BC_2020.097
Published online: 23.02.2021
Rassegne - Reviews
 
Profilo molecolare multigenico somatico di pazienti affette da cancro ovarico sieroso ad alto grado a lunga sopravvivenza e BRCA-negative
Molecular profile of BRCA-negative long survivor High Grade Serous Ovarian Cancer patients using a somatic multigene panel
<p>Introduction: High Grade Serous Ovarian Cancer (HGSOC) is the most common subtype of ovarian cancer. Approximately half of HGSOCs are characterized by inactivation of Homologous Recombination (HR) genes, such as BRCA1/2. Given the practical certainty of recurrence in relapsed HGSOC after platinum-based chemotherapy, a maintenance approach with Poly-ADP Ribose Polymerase inhibitors (PARPi) has improved progression-free survival in BRCA1/2 mutated patients. Besides BRCA1/2 defects, there are no predictive biomarkers for sensitivity to platinum-based chemotherapy and PARPi. Molecular studies of BRCA-negative long survivor patients could be of help in identifying additional biomarkers of prolonged response.<br />Methods: a total of 20 fresh frozen tumor samples obtained from long survivor BRCA-negative HGSOC patients were investigated using a Next Generation Sequencing (NGS) multigene panel. Nucleotide variants and copy number variations of ATM, BARD1, BRIP1, CDH1, CHEK2, NBN, PALB2, PTEN, RAD51C, RAD51D, STK11 and TP53 genes were tested.<br />Results: in this cohort 17 mutated subjects (17/20; 85%) with 15 pathogenic/variants of unknown clinical significance (VUS) in TP53 have been found; nucleotide variants have been identified also in ATM (n=1), PALB2 (n=1), BRIP1 (n=2), BARD1 (n=1) and NBN (n=1).<br />Discussion: the durable response to therapy observed in our patients may be multifactorial and partially driven by germline/somatic mutations in HR genes. An extended investigation is mandatory to obtain a more comprehensive overview on the genetic status of this selected cohort of patients. Querying genes other than BRCA1/2 would be of an extremely important benefit, allowing the clinicians to evaluate the correlation between molecular and clinical features and to acquire more appropriate genetic information useful in the eligibility to target therapy.</p>
TAG: cancro ovarico   BRCA-negative   HRD  
Biochimica Clinica 2021; 45(1) 035-043
DOI: 10.19186/BC_2020.070
Published online: 24.11.2020
Contributi Scientifici - Scientific Papers
 
Il calcolo del kappa index come valida alternativa alla determinazione delle bande oligoclonali nell’iter diagnostico dei pazienti con sclerosi multipla
The Kappa Index as a valid alternative to oligoclonal bands determination in the diagnostic process of patients with multiple sclerosis
<p>Introduction: the role of the kappa free light chains (KFLC) index in the diagnostic workup of multiple sclerosis (MS) is still a matter of debate.<br />Methods: 667 subjects from three reference laboratories have been enrolled, including 181 MS patients and 486 controls with other immune-mediated or non-inflammatory disorders. Serum and cerebrospinal fluid KFLC index, serum and cerebrospinal fluid albumin and IgG concentrations were measured on BNII nephelometer (Siemens Healthineers. Marburg. Germany), while oligoclonal bands (OCB) were detected by isoelettrofocusing on Hydrasys system (Sebia. Bagno a Ripoli. Italia).<br />Results: KFLC index was higher in MS than in controls [median (interquartile range - IQR) 76.56 (35.05) versus 17.99 (2,34), p &lt;0.001]. A cut-off of 5.0 resulted in 93.9% (min-max 82.6-96.0) sensitivity and 77.4% (70.3-80.3) specificity, with positive and negative predictive values of 60.7% (41.4-69.3) and 97.2% (93.6-98.0), respectively. OCB assessment yielded 94.6% (87.9-96.5) sensitivity and 91.4% (86.6-94.8) specificity, with positive and negative predictive values of 87.5% (78.6-92.0) and 96.4 (93.6-98.0), respectively. The three laboratories showed similar results, making it possible to adopt common thresholds. The relatively low specificity of KFLC may be related to the characteristics of the control population, in particular to the percentage of subjects with inflammatory conditions associated with intratechal immunoreactivity.<br />Conclusions: an algorithm for the diagnostic management of MS could be suggested based on the KFLC index as screening test, followed by the detection of OCB, in case of a positive result. Future studies are needed to evaluate possible relationships between KFLC index, as a quantitative variable, and other clinical features of MS, such as severity of the disease and prognostic scores.</p>
TAG: kappa index   sclerosi multipla   bande oligoclonali  
Biochimica Clinica 2021; 45(1) 044-051
DOI: 10.19186/BC_2020.087
Published online: 14.01.2021
Contributi Scientifici - Scientific Papers
 
Approcci diagnostici innovativi per le malattie infiammatorie croniche intestinali
New diagnostic approaches for inflammatory bowel diseases
<p>Inflammatory bowel diseases (IBD), that include ulcerative colitis (UC) and Crohn&rsquo;s disease (CD) are among the most serious and perplexing digestive diseases. Indeed, diagnosis is sometimes delayed due to the variability and subtlety of its initial manifestations, especially in CD. Since no gold standard is currently defined for the diagnosis and monitoring of IBD, a number of genomic, metabolomic and proteomic studies have tried to address this issue. After illustrating the traditional diagnostic approach (mainly fecal calprotectin), this Opinion Paper reports about the utility of some new biomarkers (micro-RNA, proteomic and metabolomic markers). In particular, the results of a study on fecal peptides are commented. After verifying that proteolytic degradation was clearly visible in fecal samples of a number of control (n=34) and patients with IBD (n=133), the matrix-assisted laser desorption ionization (MALDI) time of flight (TOF) mass spectrometry was used to evaluate peptides patterns of fecal samples, in a range from 1000 to 4000 Da. This cohort was used to derive an algorithm for IBD diagnosis. Diagnostic performances were then estimated using an additional validation cohort, including subjects with IBD (n=42) and without IBD (n= 28). Sensitivity was 54.8% (95%CI: 38.7%&ndash;70.2%) and specificity 96.4% (95%CI: 81.7%&ndash;99.9%) with a positive and a negative predictive value of 95.8% (95%CI: 76.7%&ndash;99.4%) and 58.7% (95%CI: 50.3&ndash;66.6%), respectively. In comparison, fecal calprotectin, achieved sensitivity and specificity of 78.6% (95%CI: 63.2%&ndash;89.7%) and 42.9% (95%CI: 24.5%&ndash;62.8%). In spite of the obtained good diagnostic performances, any candidate biomarker, once identified, should be carefully validated before being translated into clinical practice.</p>
TAG: proteomica   peptidomica   malattie infiammatorie croniche  
Biochimica Clinica 2021; 45(1) 052-056
DOI: 10.19186/BC_2020.105
Published online: 23.02.2021
Opinioni - Opinions
 
Introduzione ai Big Data e all’Intelligenza Artificiale in Medicina di Laboratorio
Introduction to Big Data and Artificial Intelligence in Laboratory Medicine
<p>Currently, thanks to the growing computing capacity and the increasing availability of digital data, Data Science is playing an important role in the future development of Laboratory Medicine. However, the concepts of Big Data (BD) and Artificial Intelligence (AI) can still be interpreted in various ways. Clinical laboratories are certainly among the health care organizations producing an important number of data that can be considered BD and it is certainly not a coincidence that they are among the first health organizations to have implemented computer systems within their workflows. Through a process called Data Mining it is possible to extract useful information from BD using automatic or semi-automatic methods that must be preceded by Data Cleaning in order to ensure the cleanliness and correctness of the data themself. Regarding Data Analysis, several Machine Learning or Deep Learning techniques based on different algorithms or on the functioning principle of neural networks can be used; for the development of these techniques, R and Python programming languages are really useful. Although many applications can be useful in Laboratory Medicine, there are still some obstacles to overcome, including poor harmonization of data or fragmentation of sources; moreover, the issue of data accessibility must be managed considering patient&rsquo;s privacy as a priority. Finally, there is an increase apprehension related to the awareness of the inevitable innovation in the Laboratory Medicine field in the near future, because of these new approaches. To face these challenges, it is necessary that these topics become familiar to the professionals of Laboratory Medicine. Aim of this Document is to share information about BD and AI in order to contribute to the introduction and development of these methodologies in the field of Laboratory Medicine.</p>
TAG: medicina di laboratorio   big data   intelligenza artificiale  
Biochimica Clinica 2021; 45(1) 057-067
DOI: 10.19186/BC_2020.085
Published online: 22.12.2020
Documenti - Documents
 
Biomarcatori cardiaci: dove stiamo andando?
Cardiac biomarkers: where are we going?
<p>The measurement of cardiac troponins (cTn) is recommended by all guidelines as the gold standard for the detection of differential myocardial injury and acute myocardial infarction (AMI). In this article, some key issues regarding both analytical characteristics of the high-sensitivity methods for cTn, which are still considered controversial or unresolved are discussed in details. These issues have been included in the activities of the Joint Working Group on &ldquo;Cardiac Biomarkers&rdquo; of the Italian Society of Clinical Biochemistry and the Italian branch of the European Ligand Assay Society. The major clinical concern regarding hs-cTn methods is the difficulty to differentiate the pathophysiological mechanism responsible for biomarker release from cardiomyocytes after reversible or irreversible injury, respectively. High-sensitivity cTnI and cTnT methods (hs-cTn) enable to monitor myocardial renewal and remodelling, and to promptly identify patients at highest risk of heart failure. In addition, several studies demonstrated that the cardiovascular risk progressively increases in the general population even for hs-cTn values well below the 99th percentile, i.e. the recognized cut-off for the detection of myocardial injury and diagnosis of AMI. An early and effective treatment of individuals at higher cardiovascular risk may revert the initial myocardial remodelling and slow down heart failure progression. Finally, recent studies support the working hypothesis that a new generation of hs-cTn methods should be set up based on monoclonal antibodies, specific for circulating peptide forms more characteristics for reversible rather than irreversible myocardial injury. Of course, screening programs of cardiovascular risk stratification and prevention strategies using hs-cTn methods require further investigation to define the optimal target populations, timing of measurement, and preventive interventions.</p>
TAG: biomarcatori   troponine cardiache   metodi ad alta sensibilità  
Biochimica Clinica 2021; 45(1) 068-074
DOI: 10.19186/BC_2020.088
Published online: 22.12.2020
Documenti - Documents
 
Revisione e aggiornamento del documento di consenso SIBioC per la ricerca e quantificazione della proteina di Bence Jones
Update of the Italian Society of Clinical Biochemistry (SIBioC) Consensus document on the detection and quantification of the Bence Jones protein
<p>Bence Jones protein (BJP) refers to urine monoclonal free immunoglobulin light chains produced by the clonal expansion of a plasma cell in the bone marrow. BJP is strongly associated with systemic amyloidosis AL, light chain deposition disease, and multiple myeloma; less frequently, BJP may be recognized either in patients with monoclonal gammopathies of uncertain significance (MGUS) and with other plasma cell dyscrasias or in patients with malignant non-Hodgkin&#39;s lymphomas and chronic lymphocytic leukemia. This paper contains updated recommendations for the detection and the measurement of BJP in clinical practice from the Working Group &ldquo;Proteins&rdquo; of the Italian Society of Clinical Biochemistry (SIBioC), with specific indications for improving all the steps of the preanalytical, analytical, and postanalytical phases. The first morning void is the urine sample recommended for BJP detection, while 24-hours urine collection is preferred for BJP quantification. Native urine cannot be used for samples with low or very low content in urine total protein; in these cases, samples should be concentrated by using specific disposables, such as ultrafiltration membranes retaining proteins with molecular weight around 10 kDa. The required degree of concentration may vary according to sensitivity of the electrophoretic method utilized and the protein content of the sample. The detection of BJP may be performed directly by the recommended method agarose gel immunofixation (IFE) with specific polyvalent immunoglobulin antisera IgG-IgA-IgM, total  and  light chains; alternatively, an electrophoretic screening may be acceptable to rule out negative test results. However, positive test results should be confirmed by IFE. Tests based on immunometric methods can be used neither as screening test, nor for the BJP quantification; however, it could be useful for monitoring purposes, provided that the renal function of the patient is preserved. BJP measurement should be performed by the densitometric scanning of the electrophoretic peak corresponding to BJP, and results should be expressed as ratio of the BJP peak percentage to the urine total protein. Test results should be always integrated by standardized interpretative comments included in the laboratory reports.</p>
TAG: proteina di Bence Jones   discrasia plasmacellulare   catene leggere libere  
Biochimica Clinica 2021; 45(1) 075-086
DOI: 10.19186/BC_2020.084
Published online: 16.10.2020
Documenti SIBioC - SIBioC Documents
 
Cinetica e caratteristiche biologiche della risposta umorale all’infezione da SARS-CoV-2: implicazioni vaccinali
Kinetics and biological characteristics of humoral response developing after SARS-CoV-2 infection: implications for vaccination
<p>With the ongoing coronavirus disease 2019 (COVID-19) pandemic outbreak spreading all around the world, an extensive vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now universally regarded as one of the most effective strategies for counteracting the unremittent spread of this novel coronavirus. Nonetheless, the reasonable need to identify segments of the population in which vaccination shall be prioritized for avoiding a possible shortage of vaccines seems to collide with indications provided by many national and international healthcare organizations, that endorse widespread vaccination irrespective of a positive history of prior symptomatic or asymptomatic SARS-CoV-2 infection. To this end, this document provides an ad interim guidance aimed at prioritizing SARS-CoV-2 vaccination in people who are more likely to be infected, re-infected and/or to develop more aggressive COVID-19 illness, essentially based on routine assessment and monitoring of anti-SARS-CoV-2 immune response.</p>
TAG: COVID-19   anticorpi   vaccino  
Biochimica Clinica 2021; 45(1) 087-090
DOI: 10.19186/BC_2021.001
Published online: 11.01.2021
Documenti SIBioC - SIBioC Documents
 
Raccomandazioni ad interim di SIBioC per l’analisi sierologica dell’infezione da SARS-CoV-2
Ad interim SIBioC recommendations for serological assessment of SARS-CoV-2 infection
<p>The recent pandemic outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and associated with the pathology called COVID-19 (coronavirus disease 2019), has now become one of the most strenuous health care challenges since the emergence of the three pandemics caused by influenza viruses during the past century. Throughout the clinical decision-making of COVID-19, laboratory tests are essential for supporting the screening, diagnosis, prognostication and therapeutic monitoring of this severe infectious disease. Serological testing, that reflects the humoral immune response developing after interaction between the host and the virus (or its components), enables to garner a vast array of clinical information which can be especially used in seroprevalence or seroconversion studies. To this end, the Task Force on COVID-19 of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) has endorsed a series of technical, practical and clinical ad interim recommendations, aimed at facilitating and optimizing the introduction, clinical usage and governance of SARS-CoV-2 serological immunoassays in routine practice.</p>
TAG: coronavirus   SARS-CoV-2   COVID-19  
Biochimica Clinica 2021; 45(1) 091-099
DOI: 10.19186/BC_2021.002
Published online: 22.01.2021
Documenti SIBioC - SIBioC Documents
 
Lab Tests Online Italia. Attività del 2020
TAG: LabTest   risultati   SIBioC  
Biochimica Clinica 2021; 45(1) 100
DOI: 10.19186/BC_2021.004
Notizie SIBioC - SIBioC News
 
Il valore aggiunto della diagnostica molecolare nelle forme monogeniche di diabete mellito
Advantages of molecular diagnosis in monogenic diabetes
<p>Maturity Onset Diabetes of the Young (MODY), the most frequent form of monogenic diabetes, comprises a group of heterogeneous disorders, characterized by non-autoimmune diabetes due to mutations of at least 14 different genes.<br />We report a case of a 38-years-old patient with non-autoimmune diabetes, where molecular analysis evidenced a large deletion on chromosome 17q12 including several genes, among them HNF1&beta; associated to MODY5. The analysis allowed us to clarify the complex phenotype of the patient including, in addition to diabetes, intellectual disability, seizures, kidney cysts and facial dimorphisms. This case shows that diabetes when caused by large deletions, can be just one of the symptoms of a &ldquo;clinical syndrome&rdquo; that includes other features due to the deletion of neighboring genes and confirms the important role of the molecular test to obtain a correct diagnosis in a patient with a suspicion of monogenic diabetes.</p>
TAG: diabete mellito   diagnostica molecolare   MODY  
Biochimica Clinica 2021; 45(1) e1-e3
DOI: 10.19186/BC_2020.060
Published online: 24.11.2020
Casi Clinici - Case Report
 
Rischio clinico ed ematologia di Laboratorio: è possibile affidarsi al solo Volume Corpuscolare Medio per scoprire l’errata identificazione del paziente?
Clinical risk management in laboratory haematology: is Mean Corpuscular Volume a reliable marker to recognize identification errors?
M. Berardi  |  F. Balboni  |  S. Buoro  | 
<p>Identification errors in laboratory medicine are a major issue. Delta checks rules have a fundamental function to identify this type of errors. In the haematology section of the laboratory, the mean corpuscular volume (MCV) is one of the parameters which delta checks rely on. Unfortunately, this approach is sub-optimal since many patients show similar MCV. We present here a case illustrating the problem and the potential drawbacks for patient safety.</p>
TAG: volume corpuscolare medio   ematologia   rischio clinico  
Biochimica Clinica 2021; 45(1) e4-e6
DOI: 10.19186/BC_2020.079
Published online: 24.11.2020
Casi Clinici - Case Report
 
Inspiegabili alterazioni di esami coagulativi
Unexpected coagulation test abnormalities
<p>A 72 year-old female was screened before a minor orthopaedic surgery with routine coagulation tests, that resulted highly altered. Prothrombin time and activated partial thromboplastin time (PT and aPTT) could not be calculated because the system registered a biphasic curve, protein C and protein S (PC and PS) levels were not measurable and antiphospholipid antibodies were highly positive. Reviewing previous laboratory findings, a serum protein electrophoresis showing the presence of a monoclonal peak in the gamma region was retrieved. A serum immunofixation was then performed, and an IgM kappa monoclonal component was typed; a cryoglobulin test was positive for cryoglobulin type II. To investigate the possible relationship between these laboratory findings, a pool of normal plasma was spiked with the patient IgM monoclonal component at progressively higher concentrations registering a prolongation of PT and aPTT and a slight reduction of PC and PS. The presence of an IgM paraprotein, although not quantitatively relevant, was therefore functionally able to interfere with the coagulation time calculation system. Although coagulation abnormalities in monoclonal gammopathy of undetermined significance are uncommon, these should be attentively investigated, to guarantee a correct laboratory report.</p>
TAG: coagulazione   MGUS   crioglobuline  
Biochimica Clinica 2021; 45(1) e7-e10
DOI: 10.19186/BC_2020.090
Published online: 24.02.2021
Casi clinici - Case report
 
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