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Biochimica Clinica: VOL.44 N.3

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Una lezione che arriva da lontano
P. Pezzati  | 
TAG: certificazione ISO   metodiche analitiche   Africa Health Agenda International Conference  
Biochimica Clinica 2020; 44(3) 215-216
DOI: 10.19186/BC_2020.064
Published online: 26.08.2020
Editoriale - Editorial
Gestire, integrare e comunicare l’informazione di laboratorio: il futuro della medicina di laboratorio
TAG: medicina di laboratorio   diagnostica biochimica   informazioni diagnostiche  
Biochimica Clinica 2020; 44(3) 217-218
DOI: 10.19186/BC_2020.066
Published online: 26.08.2020
Editoriale - Editorial
Il deficit di G6PD in Medicina di Laboratorio
G6PD deficiency in Laboratory Medicine
<p>Glucose 6-phosphate dehydrogenase has a key role in the production of the reducing power necessary to face oxidative stress and for providing ribose, which is a basic constituent of nucleic acids. It is therefore not surprising that the gene is present in all organisms, and that is also highly conserved during the evolution. The occurrence of G6PD mutants may have important consequences in carriers, depending on the class of the mutants, triggering events and various comorbidities. Acute and chronic hemolytic anemias are the most typical clinical hallmarks. The determination and characterization of G6PD can be achieved by qualitative tests, various quantitative catalytic activity determinations, and by molecular biology techniques. Sample collection and stability is not a critical problem, but some pre-analytical conditions in vivo(previous transfusions, recent blood losses) should be known by the laboratory before measuring G6PD. A number of quantitative methods is available and there is no consensus on the measuring temperature (30 or 37&deg;C) and on the reference ranges. The consequence is that the state-of-the-art of the various methods is variable, as clearly proven from recent EQAS analyses. Moreover, analytical goals have not been defined yet. In conclusion, we believe that this test needs better attention from laboratory professionals in order to offer an improved service to patients with G6PD deficiency anemias and related complications.</p>
TAG: G6PD   NADPH   diagnostica molecolare  
Biochimica Clinica 2020; 44(3) 219-231
DOI: 10.19186/BC_2020.040
Published online: 08.07.2020
Rassegne - Reviews
Effetti della restrizione calorica sullo stress ossidativo nell'obesità: sono miglioramenti transitori?
Effect of caloric restriction on oxidative stress in obesity: are these transient improvements?
A. Bolner  |  A. Vanzo  |  D. Giavarina  |  G. Nordera  |  O. Bosello  | 
<p>Background: the effects of caloric restriction (CR) on oxidative stress in obesity has been previously studied using markers that not always were able to describe all the components of the oxidative-inflammatory picture.<br />Methods: in this study, the redox state of 20 obese was evaluated at baseline and after 30 and 60 days of CR using a complete panel of markers: the majority of them were determined using HPLC methods.<br />Results: before CR (V0), serum peroxides (dROMs) were very high, total antioxidant barrier (BAP) was at the lower limit of the reference interval and C-reactive protein (hsCRP) was increased; on the opposite, glutathione was well within the reference intervals in both total and reduced form. Despite the imbalance of the dROMs/BAP equilibrium, the markers of oxidative damage, such 3-nitrotyrosine (3NT) and 8-hydroxy-deoxyguanosine (8OHdG), index of a mild oxidative-inflammatory imbalance, were not particularly relevant.<br />After 30 days of CR (V30), in addition to the slight improvements of glucose, fructosamine and HOMA-IR, hsCRP was decreased, while BAP and total glutathione were increased, with consequent improvement of the oxidative stress-inflammatory balance (oxidative-inflammation). After 60 days of CR (V60) the improvements observed at V30 appeared to be slowing down for glucose and fructosamine, in slight inverse tendency for HOMA-IR and hsCRP, and decreasing for BAP and glutathione. The slight increase of inter-quartile range (IQR) of 3NT showed a lower counter-regulatory antioxidant response capacity, as if the ameliorative effects of CR in the first period had turned off.<br />Conclusion: the improvements of the oxidative-inflammatory equilibrium appear to be transient in the course of CR. The rearrangements of the gut microbiota during CR and the consequent epigenetic modulations could be responsible for this peculiar trend.</p>
TAG: obesità   microbioma   glutatione  
Biochimica Clinica 2020; 44(3) 232-238
DOI: 10.19186/BC_2020.016
Published online: 06.03.2020
Contributi Scientifici - Scientific Papers
ISO 15189 all'ombra dell'Equatore. Descrizione dell’esperienza del North Kinangop Catholic Hospital Laboratory in Kenya
ISO 15189 in the shadow of the Equator. Description of the experience in the North Kinangop Catholic Hospital Laboratory (Kenya).
<p>Introduction: it is nowadays recognized that, in low income countries, the development of quality-assured laboratory services is a major part of a greater framework of health system strengthening and that limited laboratory capacity represents a major barrier to implementation and sustainability of prevention, treatment and care programs. Acknowledging this need, the North Kinangop Catholic Hospital clinical laboratory (Kenya) pursued and obtained ISO 15189 accreditation in clinical biochemistry and haematology.<br />Methods: the present paper describes the steps that led to this accomplishment in January 2019, as a result of a three-year project. Methodological support was provided by the School of Medicine (Maryland University, USA) as part of an American government program aimed to reinforce laboratory services in resource-poor countries. The iterative plan&ndash;do&ndash;check&ndash;act method was applied.<br />Results: major changes in laboratory management were introduced to meet the requirements of the standard. Analytical quality issues were reviewed; Internal Quality Control and External Quality Assessment procedures were implemented; reorganization of laboratory areas was made. The North Kinangop Catholic Hospital Laboratory obtained ISO 15189 accreditation in January 2019, as a result of a process started in March 2016.<br />Conclusions: a key to the success was professional commitment, sharing of values and external support, although careful planning resulted to be the key issue; actually, in low income countries social, political and even logistical peculiarities pose unique challenges.</p>
TAG: diagnostica di laboratorio   laboratorio clinico   accreditamento  
Biochimica Clinica 2020; 44(3) 239-248
DOI: 10.19186/BC_2020.023
Published online: 14.04.2020
Contributi Scientifici - Scientific Papers
Pharmacogenetic markers able to predict lipid-related parameters in a cohort of ritonavir treated patients
<p>Introduction: Ritonavir (RTV) could cause lipodistrofy and body fat redistribution. Pharmacogenetics could explain part of variability in RTV treatment outcome, but few data are present in literature concerning its influence on lipid-associated parameters. For these reasons, aim of this study is to describe the role of single nucleotide polymorphisms (SNPs) in genes involved in lipids and RTV transport and metabolism in affecting lipid-related biomarkers in a cohort of HIV-infected patients.<br />Methods: adult HIV-affected patients, being on RTV-containing antiretroviral treatment for at least 6 months, were enrolled at the &ldquo;Amedeo di Savoia&rdquo; hospital in Turin (Italy). Genotypes were assessed through real-time PCR.<br />Results: 99 patients were recruited for the study. The following associations were suggested: ABCB13435 TT on total cholesterol and triglycerydes, ABCB12677 on viral load, ABCC2-1249 AA on glucose,ABCC2 -24 GA/AA on total cholesterol, low density lipoproteins cholesterol and triglycerides, ABCG21194+928 CC on pancreatic amylase, HNF4 975 CG/GG on total cholesterol, low density lipoproteins cholesterol, VEGF-1154 AA on lactate dehydrogenase.<br />Discussion: This work was the first analyzing genetic polymorphisms affecting lipid-related markers in a cohort of RTV-treated patients. Further analyses are warranted to confirm these data and evaluate their influence on cardiovascular risk.</p>
TAG: HIV   SNPs   cholesterol  
Biochimica Clinica 2020; 44(3) 249-254
DOI: 10.19186/BC_2020.031
Published online: 08.07.2020
Contributi Scientifici - Scientific Papers
A wide next-generation-sequencing panel improves the molecular diagnosis of dyslipidemias
<p>Introduction: dyslipidemias are common clinical conditions associated to cardiovascular diseases. Among these, Familial Hypercholesterolemia (FH) and severe Hypertriglyceridemia (sHTG) are the most frequent ones. The aim of this study is to evaluate the possible use of a wide next-generation-sequencing (NGS) panel of 28 genes involved in lipid metabolism, to improve the molecular diagnosis of dyslipidemias.<br />Methods: a reanalysis of 25 patients (21 FH and 4 sHTG) previously analyzed for a few causative genes has been carried on. Patients bearing different types of variants [single nucleotide variants (SNVs) and copy number variations (CNVs)] in different genes, previously analyzed with Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) have been selected. DNA libraries have been prepared using Agilent SureSelect target enrichment protocol; the sequencing has been performed using Illumina MiSeq (V2 150x2 Micro). The results of the sequencing have been evaluated by Agilent SureCall and Agilent Alissa Align&amp;Call and Intrepret pipelines.<br />Results: all previously identified SNVs and CNVs have been confirmed by NGS. Additional rare variants, not always associated with dyslipidemias, were found in 23/25 patients. An additional pathogenic variant in the APOBgene has been identified in a sHTG patient carrying only 1 pathogenic variant in the APOA5gene (causative of sHTG).<br />Conclusions: the NGS-method confirmed all the results obtained with direct sequencing and MLPA methodologies. Additional rare variants were detected, even if most of them turned out to be variant of uncertain significance (VUS). In conclusion, this NGS approach may enhance the molecular diagnosis of different types of dyslipidemias, thereby leading to a better understanding and detection of complex phenotypes.</p>
TAG: dyslipidemias   molecular diagnosis   next-generation-sequencing  
Biochimica Clinica 2020; 44(3) 255-262
DOI: 10.19186/BC_2020.038
Published online: 08.07.2020
Contributi Scientifici - Scientific Papers
Il futuro della Medicina di Laboratorio: un Manifesto per i suoi professionisti
Future of laboratory medicine: a Manifesto for laboratory professionals
M. Plebani  | 
<p>In the last decades, the landscape of clinical laboratories has experienced monumental changes due to both technological developments and new challenges. Laboratory medicine has been strongly influenced by technological developments, but also by a wide range of other issues such as the healthcare system organization, medical practice and, more recently, patient empowerment. In the coming decade, many and different trends will intersect, interact, and over lap each other, and with current laboratory practices. These dramatic innovations make of critical importance for leaders to prepare for a future with the understanding of possible collisions between linear trends and nonlinear external forces. The aim of the present paper is to discuss the future of clinical laboratories according to two different approaches: technological and professional viewpoints. In particular, a revised version of the &ldquo;ten points manifesto&rdquo; for the future of laboratory professionals is described, with a focus on the main drivers and efforts that should be done to demonstrate the added value and true role of laboratory medicine in modern health care systems. The main goal of the manifesto is to emphasize the central role and the vital contribution of clinical laboratories and their professionals to improved health care, patient safety and clinical outcomes.</p>
TAG: medicina di laboratorio   esami di laboratorio   brain-to-brain loop  
Biochimica Clinica 2020; 44(3) 263-269
DOI: 10.19186/BC_2020.030
Opinioni - Opinions
Misura e identificazione delle componenti monoclonali plasmatiche: risultati di uno studio multicentrico internazionale
The measurement and the identification of plasma monoclonal proteins: results from an international multicentre study.
M. Mussap  | 
<p>The measurement of monoclonal proteins (MP) is basic for diagnosis, risk stratification, and evaluation of the response to the therapeutic treatment of plasma cells dyscrasias and lymphoproliferative disorders. Quality specifications of the MP measurement have been evaluated in a multicentre study involving 14 clinical laboratories and 2 In vitro Diagnostics Companies across three continents. Aliquots of human serum pools with normal, hypo- and hyper &gamma;-globulinemia spiked with different amounts of therapeutic monoclonal drugs migrating in the &gamma;-globulin zone, mimicking a MP and serum aliquots with a MP migrating in &beta;-globulin zone were distributed to participants. Two articles, published in Clinical Chemistry and Laboratory Medicine, reported detailed results emerging from the study; the most significant have been condensed in the present paper. The MP concentration, the amount of the co-migrating proteins, especially the polyclonal immunoglobulins background, and the MP migration pattern significantly affect accuracy and precision of the MP quantification. When MP is &lt;1 g/L, the unacceptable imprecision and the loss of accuracy, strongly discourage to report any numeric data, even though the presence of MP in the serum protein electrophoresis (SPE) must be reported qualitatively. The two gating techniques, namely perpendicular drop (DP) and tangent skimming (TS), lead to overestimation and underestimation of small MP, respectively. All the tested SPE methods, two agarose gel- and one capillary zone electrophoresis, detected 100% of MP &ge;1 g/L; as expected, the limit of detection of immunofixation and immunosubtraction were moderately more sensitive. The overall mean intra-laboratory coefficient of variation (CV) for MP ranging 1-10 g/L was found around 5.0%; thus, the monitoring of changes in MP level over time within the same laboratory is considered reliable provided that the intensity of the polyclonal background remains stable.</p>
TAG: profilo proteico   elettroforesi capillare zonale   componente monoclonale  
Biochimica Clinica 2020; 44(3) 270-278
DOI: 10.19186/BC_2020.033
Published online: 08.07.2020
Opinioni - Opinions
Valutazione precoce del danno cardiaco da farmaci chemioterapici: importanza della misura delle troponine cardiache I e T con metodi ad alta-sensibilità analitica
High-sensitivity cardiac troponin I and T methods for the early detection of myocardial injury in patients on chemotherapy
<p>Important advances achieved in pharmacological cancer treatment have led progressively to a reduction in mortality from many forms of cancer, and increasing numbers of previously incurable patients can now hope to become cancer-free. Yet, to achieve these improved outcomes a high price has been paid in terms of untoward side effects associated with treatment, cardiotoxicity in particular. Several recent studies have reported that cardiac troponin assay using high-sensitivity methods (hs-cTn) can enable the early detection of myocardial injury related to chemotherapy or abuse of drugs that are potentially cardiotoxic. Several authors have recently suggested that changes in hs-cTn values enable the early diagnosis of cardiac injury from chemotherapy, thus potentially benefitting cancer patients with increased troponin values by initiating early cardioprotective therapy. However, large randomised clinical trials are needed in order to evaluate the cost/benefit ratio of standardised protocols for the early detection of cardiotoxicity using the hs-cTn assay in patients treated with chemotherapy.</p>
TAG: danno miocardiaco   troponine cardiache   metodi ad alta sensibilità  
Biochimica Clinica 2020; 44(3) 279-286
DOI: 10.19186/BC_2020.062
Published online: 09.07.2020
Documenti SIBioC - SIBioC Documents
Il contributo del laboratorio alla corretta gestione del paziente in terapia ipolipemizzante: le raccomandazioni di EFLM e della Società Europea di Aterosclerosi (EAS)
TAG: apolipoproteina   malattia cardiovascolare aterosclerotica   particelle LDL  
Biochimica Clinica 2020; 44(3) 287-289
DOI: 10.19186/BC_2020.078
Published online: 26.08.2020
Documenti SIBioC - SIBioC Documents
Quantificazione delle lipoproteine aterogeniche per le terapie ipolipemizzanti: Raccomandazioni di Consenso della European Atherosclerosis Society (EAS) e di EFLM
Quantifying atherogenic lipoproteins for lipid-lowering strategies: consensus-based recommendations from EAS and EFLM
<p>The joint consensus panel of the European Atherosclerosis Society (EAS) and the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) recently addressed present and future challenges in the laboratory diagnostics of atherogenic lipoproteins. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), LDL cholesterol (LDLC), and calculated non-HDLC (=total &ndash; HDLC) constitute the primary lipid panel for estimating risk of atherosclerotic cardiovascular disease (ASCVD) and can be measured in the nonfasting state. LDLC is the primary target of lipidlowering therapies. For on-treatment follow-up, LDLC shall be measured or calculated by the same method to attenuate errors in treatment decisions due to marked between-method variations. Lipoprotein(a) [Lp(a)]- cholesterol is part of measured or calculated LDLC and should be estimated at least once in all patients at risk of ASCVD, especially in those whose LDLC declines poorly upon statin treatment. Residual risk of ASCVD even under optimal LDL-lowering treatment should be also assessed by non-HDLC or apolipoprotein B (apoB), especially in patients with mild-to-moderate hypertriglyceridemia (2&ndash;10 mmol/L). Non-HDLC includes the assessment of remnant lipoprotein cholesterol and shall be reported in all standard lipid panels. Additional apoB measurement can detect elevated LDL particle (LDLP) numbers often unidentified on the basis of LDLC alone. Reference intervals of lipids, lipoproteins, and apolipoproteins are reported for European men and women aged 20&ndash;100 years. However, laboratories shall flag abnormal lipid values with reference to therapeutic decision thresholds.</p>
TAG: apolipoproteina   malattia cardiovascolare aterosclerotica   particelle LDL  
Biochimica Clinica 2020; 44(3) 290-313
DOI: 10.19186/BC_2020.078
Published online: 26.08.2020
Documenti - Documents
Il ruolo del laboratorio di Biochimica Clinica nell’organizzazione di un evento sportivo internazionale: la XXX Universiade Estiva
TAG: universiadi   indagini ematochimiche   intervalli di riferimento  
Biochimica Clinica 2020; 44(3) 314-317
DOI: 10.19186/BC_2020.044
Published online: 09.07.2020
Lettere all'Editore - Letters to the Editor
Il sedimento urinario: atlante per immagini
M. Plebani  | 
Biochimica Clinica 2020; 44(3) 318-319
DOI: 10.19186/BC_2020.080
Published online: 26.08.2020
Recensioni - Book Review
In ricordo di Jan-Olof Jeppsson
A. Mosca  |  V. Bianchi  | 
Biochimica Clinica 2020; 44(3) 320
DOI: 10.19186/BC_2020.065
Published online: 14.07.2020
Notizie SIBioC - SIBioC News
52° Congresso Nazionale: Virtual Edition
Biochimica Clinica 2020; 44(3) 321
DOI: 10.19186/BC_2020.083
Published online: 26.08.2020
Notizie SIBioC - SIBioC News
Una variante emoglobinica rara
A rare hemoglobin variant
<p>When arrived to our observation, BS was an African origin newborn of a few days. His hemoglobin concentration and complete blood count were within normal ranges, and he had no jaundice; however, his parents are heterozygous carriers of hemoglobin variant: HbC trait the mother and HbS trait the father. Screening was therefore required for hemoglobin variants. The request is appropriate since the evidence of a double heterozygosis S/C (SCD) would allow timely treatment of these patients. Screening was performed in capillary electrophoresis but was not conclusive because the presence of a small concentration of HbS and of another variant did us not allow to make a diagnosis, although the presence of HbA allowed to exclude the state of SCD. Hemoglobin electrophoresis was then performed, but it was not conclusive. It was necessary resorting to the molecular analysis, that highlights the presence of HbS trait and a mutation in heterozygosis at the charge of the gamma-globin chain consistent with HbF Granada. The recognition of HbF Granada was meaningless from a clinical point of view, but allowed to exclude the presence of a hemoglobin compound, the main clinical question of this clinical case.</p>
TAG: emoglobinopatia   screening neonatale   elettroforesi capillare  
Biochimica Clinica 2020; 44(3) e019-e021
DOI: 10.19186/BC_2020.035
Published online: 08.07.2020
Casi Clinici - Case Report
È tempo di ridefinire gli intervalli di riferimento e terapeutici della cupruria nella malattia di Wilson?
Is it time to redefine cupruria reference and therapeutic intervals in Wilson's Disease?
<p>Wilson&rsquo;s Disease (WD) is an autosomal recessive genetic disease caused by mutations to the copper-transporting gene <em>ATP7B</em>. WD leads to hepatic copper retention with subsequently clinical manifestations in different organs. The biochemical diagnostic approach includes measurement of serum ceruloplasmin levels and 24-hour urinary copper excretion (uCu/24h). WD patients are generally treated with D-penicillamine and cupruria is necessary to confirm the efficacy of maintenance treatment and the patient&#39;s adherence to therapy. A 30-year-old man was diagnosed with WD at the age of 5 and, since then, was treated with D-penicillamine. In this patient the uCu/24h values never fell within the range recommended by International Guidelines, but no clinical or subclinical progressions of the disease were found. The information derived from this single WD patient, monitored by serial clinical and laboratory checks for more than twenty years, may be useful for a better long-term management of WD, although we suggest that multicenter studies to re-define cupruria reference and therapeutic intervals are needed.</p>
TAG: malattia di Wilson   gene ATP7B   cupruria  
Biochimica Clinica 2020; 44(3) e022-e025
DOI: 10.19186/BC_2020.041
Published online: 09.07.2020
Casi Clinici - Case Report
Una variante emoglobinica co-migrante con le normali frazioni emoglobiniche in HPLC
A hemoglobin variant co-migrating with normal hemoglobin fractions in HPLC
A. Guastini  |  LA. Rizzi  |  F. Santoni  |  S. Vinci  |  G. Barberio  |  G. Ivaldi  | 
<p>To date, approximately 1700 hemoglobin (Hb) variants have been identified, many of which are clinically silent. We report a hemoglobin variant visible only with capillary electrophoresis (CE). In a 65-year-old woman, using a high-performance liquid chromatography system (HPLC), HbF and HbA2were 19.3% and 0.7%, respectively, and no abnormal peaks were observed. Subsequent analysis by capillary electrophoresis (CE) showed an atypical profile with a clear presence of an abnormal Hb in the &quot;zone Z14&quot;. The molecular investigation of the globin genes confirmed a variation of the alpha1 c.271 A&gt; G gene corresponding to Hb Sudbury. The HPLC analysis initially led to an incorrect interpretation of defects on gamma genes with production of hereditary persistence of HbF (HPFH) and on delta genes, a delta thalassemia. The combination of different technologies (such as CE and HPLC) can certainly be useful to detect new variants of hemoglobin and allowsmore correct diagnostic conclusions.</p>
TAG: variante emoglobinica   emoglobinopatie   parametri emocromocitometrici  
Biochimica Clinica 2020; 44(3) e026-e027
DOI: 10.19186/BC_2020.076
Published online: 14.07.2020
Casi Clinici - Case Report