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
☩Howard Morris Australia
Mario Plebani Italy
Sverre Sandberg Norway
Ana-Maria Simundic Croatia
☩Jill Tate Australia
Tommaso Trenti Italy
Cas Weykamp The Netherlands
Maria Willrich USA
Paul Yip Canada

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BC: Articoli scritti da M. Plebani

Ridurre l’inappropriatezza in medicina di laboratorio: come, quando e perchè
Improving appropriateness in laboratory medicine: how, when and why
<p><span style="color:rgb(33, 29, 30); font-size:9pt">The issue of the appropriateness in laboratory medicine has been discussed from several years in association to theparallel onset of two aspects: 1) the significant increase in tests demand and utilization, thanks to the developmentof laboratory automation and information laboratory systems (LIS), that allow to provide timely and reliable results toclinicians; 2) the opportunity, thanks to new pathophysiological knowledge and new technologies to introduce newand more sophisticated tests in clinical practice, providing a relevant support to the clinician in the management ofpatients, according to the improved vision of personalized medicine. As a consequence, the potentialinappropriateness in test utilization and the need to manage demand and to reduce the redundant testing havereceived increasing concern. Several papers, in the recent literature, demonstrated that the inappropriateness inlaboratory test utilization may represent a potential source of errors, and interesting strategies have been proposedand progressively adopted in order to limit this problematic outcome. An essential issue is to assure appropriatenessnot only in test request, but in all steps of the testing cycle. In particular, some of the more relevant issues has beenlinked to: rationalization of laboratory test ordering prescription, thanks to development of a computerized clinicaldecision support systems; implementation of the reflexing tests rule; definition of the minimum retesting intervalaccording to the clinical and pathophysiological criteria; timely revision of the available panel tests in order to deletethose considered obsolete from clinical and analytical point-of-view and, finally, improving the education in demandmanagement. The &ldquo;clinical laboratory stewardship&rdquo; seems to be the new and shared strategy, that guarantees notonly the appropriate utilization and interpretation of laboratory tests improving efficacy and providing efficiency but,more importantly, the future of the discipline and the role of laboratory professionals in the context of new and morecomplicated clinical and economical scenarios.</span></p>
Biochimica Clinica ; 43(3) 305-312
Documenti SIBioC - SIBioC Documents
Garantire la comparabilità dei risultati nel rispetto dei requisiti di qualità e delle esigenze organizzative: l’esempio di una procedura operativa
How to guarantee the comparability of test results in compliance with the quality requirements andorganizational needs: the example of an operative procedure
<p>Medical laboratories are responsible for the qualityof test results, also when the same patient sample is evaluated using different analytical systems within the same lab.Indeed, as stated by ISO 15189:2012, laboratories should define means to compare procedures for evaluating thecomparability of patients&rsquo; samples results within the same healthcare system. In this study we report the approachused to define a procedure for assessing results comparability, developed in our laboratory before the ISO15189:2012 accreditation in 2016. Firstly, the approach was focused on the identification of all the different situationsthat may potentially require alignment of test results within the laboratory. Therefore, after evaluating guidelines anddocuments available in the literature, we defined a workflow applicable both to quantitative and qualitative methods.For quantitative methods, bias was estimated by means of statistical analyses such as Bland Altman and PassingBablok. For qualitative methods, results comparability was assessed by concordance. Criteria for defining theacceptability of systematic errors were also included in the procedure.</p>
Biochimica Clinica ; 43(2) 135-142
Contributi Scientifici - Scientific Papers
Gli esami urgenti nel consolidamento dei laboratori: analisi decentrate, “Point-of-Care and Near-Patient testing”
Urgent testing and laboratory consolidation: Extra-laboratory, Point-of-care and Near-Patient testing.
M. Plebani  | 
<p>Urgenttests requesting is variable across different institutions in the same country and at international level. The percentageof urgent testing has been found to be about 33% in Italy, but only some of these tests are really related to clinicalneeds. Various reports are available to document the growth of extra-laboratory testing, otherwise referred to as nearpatient, bedside or Point-of-Care testing (POCT). The key objective of extra-laboratory testing, particularly POCT, isto generate a result quickly so that appropriate treatment can be implemented rapidly, but few data are available todemonstrate an effective improvement in operational and clinical outcomes. This paper sets out the requirements fordelivering an effective extra-laboratory testing by reviewing the data of the literature as well as the performancespecifications for assuring quality and patient safety.</p>
Biochimica Clinica ; 43(2) 162-167
Opinioni - Opinion
La valutazione delle prestazioni analitiche dei laboratori mediante programmi di valutazione esterna di qualità: una analisi multifattoriale
The evaluation of laboratories’ analytical performance through external quality assessment programs: amultifaceted analysis
<p>The Italian accreditation body, Accredia, requires that clinical laboratories obtained positiveanalytical performances in the last four External Quality Assessment (EQA) surveys in order to undertake theaccreditation with flexible scope (document RT-26).<br />In addition to the choice of acceptability limits (AL), other factors contribute to define the analytical performance:nature and commutability of control materials, definition of target value (TV), homogeneous group classification, dataelaboration, procedures for outliers exclusion.<br />In this study, the creatinine performances of 106 participants, obtained in the last four surveys of the year 2017 ofthe Centre of Biomedical Research (CRB) EQA program, have been evaluated using two different AL and TV: the ALproposed by the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) and by the RegionalReference Centre of the Azienda Ospedaliera Universitaria &ldquo;Careggi&rdquo; of Firenze (Italy) (CRRVEQ); the TV assignedwith the reference method (RV) and as consensus value, i.e. median of the results obtained with the same method(AV).<br />The percentage of laboratories satisfying the RT-26 requisite was different on the basis of the AL and TV considered:with the EFLM-AL, 68.8 % laboratories complied the requisite if AV was used and 60.4% if RV was applied; with theCRRVEQ-AL, 50.0% and 48.1%, respectively.<br />These data demonstrate that harmonized criteria and procedures for evaluation of EQA results are needed to obtainhomogeneous classification of laboratories&rsquo; performance.<br />In order to support the laboratory professionals in accreditation processes and, above all, to guarantee theirperformance reliability, time has come that the Scientific Societies of Laboratory Medicine promote the merging of thedifferent Italian EQA schemes in a consolidated network of EQA providers.</p>
Biochimica Clinica ; 43(2) 168-172
Opinioni - Opinion
Laboratorio clinico: non sempre più grande è migliore
Clinical laboratories: not always bigger is better.
M. Plebani  | 
<p>Laboratory services are undergoing substantial consolidation and changes through mechanisms ranging from mergers, acquisitions and outsourcing, primarily based on the expectation towards increasing volumes, improving efficiency, and reducing cost per test. However, in laboratory medicine the relationship between volume and costs is not linear, as numerous variables may influence the comprehensive costs. In particular, the relationship between volumes and costs does not span the entire pattern of clinical laboratories: high costs are associated with low volumes up to a threshold of about one million test per year. Over this threshold, there is no linear association between volumes and costs, as the laboratory organization rather than test volumes affects the final costs more significantly. Available evidence collected in the last decades, namely data on laboratory errors and associated diagnostic errors and risk for patient harm emphasizes the need for a paradigmatic shift: from a focus on volumes and efficiency to a patient-centered vision restoring the nature of laboratory services as an integral part of the diagnostic and therapy process. In particular, the vulnerability of extraanalytical phases and the lack of reliable quality specifications in pre- and post-analytical steps do not allow an improvement in the ultimate laboratory information. Process and outcome quality indicators have been proposed as effective tools to measure and improve laboratory services by stimulating a competition based on intra- and extraanalytical performance specifications, intermediate outcomes and customer satisfaction. Rather than competing with economic value, clinical laboratories should adopt a strategy based on a set of harmonized quality indicators and performance specifications, active laboratory stewardship, and improved patient safety.</p>
Biochimica Clinica ; 43(2) 156-161
Opinioni - Opinions
Siero o plasma? Un quesito non nuovo che attende risposte nuove
Serum or plasma? An old question awaiting for new answers.
<p>There is a continual debate on what type of sample a clinical laboratory should use. While serum is still considered the gold standard and remains the required sample matrix for some assays, laboratories must consider turn-around time, which is an important metric for laboratory performance and, more importantly, plays a critical role in patient care. In addition, a body of evidence emphasize the choice of plasma samples in order to prevent modifications of some measurands due to the coagulation process and related interferences. Advantages and disadvantages of serum and plasma are discussed on the basis of current literature and evidence. In addition, data are provided on the current utilization of the matrix (serum or plasma) in Italy and in other Countries. Finally, a rational for a possible shift from serum to plasma is provided.</p>
Biochimica Clinica ; 43(2) 178-186
Documenti - Documents
In ricordo di Jillian (Jill) Tate
In memory of Jillian (Jill) Tate
Biochimica Clinica ; 43(1) 115-117
Notizia SiBioC - News SIBioC
Qualità delle raccomandazioni o raccomandazioni di qualità? Il caso antigene prostatico specifico nello screening del carcinoma della prostata
Quality of recommendations or recommandations of quality? The case of PSA-based screening for prostate cancer
M. Plebani  | 
<p>Quality of recommendations or recommandations of quality? The case of PSA-based screening for prostate cancer. The l&rsquo;US Preventive Services Task Force (USPSTF) has recently revisited the evidence on PSA-based screening for prostate cancer recognizing the consistent 25% to 30% relative reduction in deaths from prostate cancer observed in two clinical trials. The most recent Task Force recommendation statement, supported by the evidence report and systematic review, has rightly changed the recommendation for prostate cancer screening - from a grade of D to a grade of C - stating that men aged 55 to 69 years should make an informed decision whether to undergo screening. This change was based on a better understanding of the evidence supporting early detection and recognition that active surveillance, rather than treatment, of low-risk cancers was becoming much more common. The USPSTF has provided a timely and careful approach to reassessment of the benefits and harms of PSA-based screening for prostate cancer. Patients, together with their physicians, should decide whether prostate cancer screening is right for the individual patient.</p>
Biochimica Clinica ; 42(4) 318-320
Opinioni - Opinions
Specifiche di qualità, terminologia e definizione dei metodi di misura delle troponine cardiache Ie T
Quality specifications, terminology and definition of the methods for the measurement of cardiac troponins
<p>All guidelines recommend that cardiac troponin I (cTnI) and T (cTnT) should be considered the preferred biomarkers for the differential diagnosis of acute coronary syndrome (ACS), and also that the 99th upper reference population limit value for cardiac troponins should be measured with an imprecision &le;10 CV%. However, only after the year 2006, some cTn methods showed analytical performances in accordance with the quality specifications required by guidelines. The cTn methods with the best analytical performances (currently named &ldquo;high-sensitivity&rdquo; methods) should be preferred for the early diagnosis of ACS and also for risk stratification of cardiovascular disease both in general population and cardiac patients. The most recent international guidelines recommend that two basic criteria are needed to define the characteristics required for cTn immunoassays in order to be defined as &ldquo;high-sensitivity&rdquo; methods. The first criterion is that the total imprecision (CV) at the 99th percentile value should be &le;10%. The second criterion is that these methods should measure cTn concentrations at least in 50% (and ideally &gt;95%) of both healthy adult men and women with value above the assay&rsquo;s limit of detection. The aim of this SIBioC document is to discuss some critical aspects related to definition of &ldquo;high-sensitivity&rdquo; cTn methods, including: analytical performance, pathophysiological interpretations, and clinical relevance of &ldquo;high-sensitivity&rdquo; cTn assays with particular attention to routine practice of clinical laboratories in Italy, recommending the use of an accurate terminology to avoid the usage of potentially misleading terms.</p>
Biochimica Clinica ; 42(4) 335-342
Documenti SIBioC - SIBioC Documents
Comunicare i risultati critici: raccomandazioni e stato-dell’arte
Management of critical results: recommendations and state of the art
M. Plebani  | 
Biochimica Clinica ; 42(2) 093-094
Editoriale - Editorial
La check list in medicina di laboratorio quale strumento di assicurazione della qualità e sicurezza del paziente: l'esempio del prelievo venoso
Check-list in laboratory medicine: an important tool to improve patient safety. The blood collection
A. Aita  |  R. Marin  |  C. Pozzato  |  E. Piva  |  L. Sciacovelli  |  M. Plebani  | 
<p>This work aims to describe the results concerning the implementation of a check-list (CL) on blood collection procedures as a tool to prevent errors in laboratory medicine. Literature and operating procedures carried out in three outpatients phlebotomy sites (SMa, SMb, PN) were analysed to identify check-points (CPs). CL draft was evaluated by a multidisciplinary team and tested for one month (September 2014) by 25 physicians and 15 nurses. The filled in CLs were analysed together with the involved staff and a final version was released. CL effectiveness was evaluated immediately after experimentation and one year later. 5661 CL were filled in, out of 9469 venipunctures (59.8%). The percentages of CPs filled in within SMa, SMb and PN were respectively: 100% patient identification and label-sample-identification matching; 80.2, 73.1 and 51.9% vein selection; 96.7, 95.8 and 97.9% needle selection; 82.5, 85.8 and 89.9% tourniquet application time; 98.9, 97.9 and 98.7% tubes filling; 98.4, 97.4 and 98.7% tubes mixing; 27.6, 23.5 and 15% temperature transport; 16.4, 20.8 and 1.3% time transport. The percentages of unsuitable samples in SM and PN were respectively: 0.040 and 0.013% (September 2014); 0.041 and 0.012% (October 2014); 0.024 and 0.16% (September-October 2015). The insufficient number of available CLs, difficulties over communication concerning purpose and methodology, and patients crowding affected the results in SM; anyway the CL was very helpful for trainees. An effective CL should: include only critical CPs, be shared with the staff, take into account organizational peculiarities. CL is a powerful tool to ensure patient safety only when it becomes an integral part of quality management system.</p>
Biochimica Clinica ; 42(2) 131-140
Contributi Scientifici - Scientific papers
Un caso di anemia multifattoriale
A case of anemia from intricate causes
<p>A 52 year old female, born in Ecuador, was admitted to the medical ward because of dizziness, blurred vision, sweating and vomiting started 3 days earlier. Complete blood count showed a severe anemia, while mean corpuscolar volume, mean corpuscolar hemoglobin, white blood cell, differential and platelet count were normal. Biochemical tests revealed a very high LDH and a low haptoglobin value. The blood smear revealed marked anisocytosis, hypocromia, oval erythrocytes, teardrop cells and fragments, with the presence of hypersegmented neuthrophils. These morphological features, together with the information obtained by the hematology analyzers, gave rise to the suspicion of vitamin B12 deficiency. Further investigation confirmed a low level of vitamin B12. Variant hemoglobin was detected by high performance liquid chromatography and capillary electrophoresis; an elevated soluble transferrin receptor value was observed. A diagnosis of sickle cell disorder associated to alpha thalassemia with iron and B12 deficiency was formulated.</p>
Biochimica Clinica ; 42(2) e18-e21
Casi clinici - Case report
Valutazione delle caratteristiche analitiche dei metodi di misura delle troponine cardiache I e T: dalla teoria alla pratica di laboratorio. Documento congiunto del Gruppo di Studio Biomarcatori Cardiovascolari di SIBioC-Medicina di Laboratorio ed Europea
Evaluation of analytical performance of immunoassay methods for cardiac troponin I and T: from theory to laboratory practice. Joint document of SIBioC and European Ligand Assay Society
<p>All the national and international guidelines recommend that cardiac troponins (cTnI and cTnT) should be considered the preferred biomarkers for the differential diagnosis of acute coronary syndrome (ACS), and also that the 99th upper reference population limit (URL) value for cardiac troponins should be measured with an imprecision &le;10 CV%. Indeed, the measurement of the 99th URL of cTnI and cTnT is a very hard analytical challenge due to low biomarker concentrations in healthy subjects. For this reason, only after the year 2006, some manufacturers set up the first new generation of cTnI and cTnT immunoassays with improved analytical sensitivity in accordance with the quality specifications indicated by international guidelines. The most recent international guidelines recommend that immunoassays for cTnI and cTnT measurement, able to completely satisfy these quality specifications, should be defined high-sensitivity methods. These methods should be preferred for early diagnosis of ACS syndrome and also for stratification of cardiovascular risk in both general population and cardiac patients. Therefore, understanding the analytical performance of immunoassay methods for cTnI and cTnT, especially at the low normal concentration range, is critically important for both laboratory professionals and clinicians. The aim of this document is to discuss some theoretical considerations related to the definition of analytical sensitivity, as well as some critical aspects concerning the experimental protocols commonly adopted for evaluation and comparison of analytical performances of cardiac troponin immunossays.</p>
Biochimica Clinica ; 42(2) 155-166
Documenti - Documents
Il ricordo di un Maestro del laboratorio clinico: Giovanni Ceriotti
In memory of Giovanni Ceriotti
M. Plebani  | 
Biochimica Clinica ; 42(1) 83-84
Notizie SIBioC - SIBioC News
Appropriatezza della richiesta di esami ed esiti clinici: il caso delle malattie renali, tiroidee e della celiachia
Appropriateness of test request and clinical outcome: the example of kidney, thyroid and coeliac disease
<p>This document analyzes the topic of appropriateness of test request. It is organized in 4 parts. The first deals with the theme of appropriateness, the consequences of insufficient or excessive test request and the need to balance guideline indications with the clinical need of a single patient. The other 3 parts present the cases of thyroid, chronic kidney and coeliac disease. With regard to the thyroid function, population screening, excluding neonates, is not recommended; on the contrary, it is highly recommended to evaluate the thyroid function in any individual with even only a minimal clinical suspect. The thyrotropin (TSH) is the test of choice with reflex free T4 and free T3, according to specific algorithms. The contemporaneous measurement of free FT3, free FT4 and TSH, except for specific cases, should be discouraged due to the high frequency of unjustified abnormal findings. Anti-thyroperoxidase antibodies are the test of choice for autoimmune thyroid diseases. In chronic kidney disease (CKD), the estimated glomerular filtration rate (eGFR) based on serum creatinine in most cases is the best indicator of renal function, provided that creatinine is measured with the accurate enzymatic method. In borderline situations, a confirmatory eGFR calculation based on cystatin C is recommended. Urinary albumin, expressed as albumin/creatinine ratio, is an essential complement for CKD staging. The diagnosis of coeliac disease requires integration between clinical, histological and serological data. The anti-transglutaminase IgA is the test of choice; only when an IgA deficit is present, the test to be used is IgG antigliadin deamidate peptides. The genetic HLA DQ2/DQ8 test is indicated for screening of subjects at risk: if negative, coeliac disease can be excluded.</p>
Biochimica Clinica ; 41(3) 266-285
Documenti - Documents
Verso l’armonizzazione dell’analisi delle urine con striscia reattiva: il ruolo di un programma di VEQ
Towards harmonization in dipstick urinalysis: the role of EQAS
<p>We reviewed the results of our 2013 to 2016 EQAS to evaluate the performance of the most used dipstick urinalysis methods in Italy. 67,450 results from 32 control samples were analyzed by using a normalized scale. For pH, the mean of the most frequent results was 72.1%&plusmn;15.6. For specific gravity, the mean for values &lt;1.020 Kg/L was 77.9%&plusmn;9.5. For glucose detection, in negative samples 97.4%&plusmn;3.1 of dipsticks provided correct results, while for samples with 300-500 mg/L, 10.8%&plusmn;6.2 provided negative results, mainly Siemens dipsticks. For proteins, in negative samples 99.7%&plusmn;0.2 of dipsticks supplied correct results, but for samples with 100-250 mg/L of proteins 25.6%&plusmn;10.7 still resulted negative. For hemoglobin, in negative samples 94.8%&plusmn;5.5 of dipsticks provided correct results; for samples with 0.1-0.3 mg/L 10.0%&plusmn;0.8 of dipsticks resulted negative. For ketones, in negative samples 99.8%&plusmn;0.2 of dipsticks provided correct results; however, Uropaper Alpha3-9L never revealed their presence in positive controls. For leucocyte esterase, in negative samples 97.6%&plusmn;0.9 of dipsticks provided correct results. For nitrites, results were consistent both with negative and positive controls (99.3%&plusmn;0.6). For protein/creatinine ratio, in samples with ~150 mg/g 14.3%&plusmn;5.3 of dipsticks provided a normal ratio. The study demonstrates the importance of an EQAS in providing to participants an evaluation of their performance and a reliable view of the degree of harmonization among results of different types of dipsticks.</p>
Biochimica Clinica ; 41(3) 248-257
Contributi scientifici - Scientific papers
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
<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 &ldquo;highly recommended&rdquo;, 2 &ldquo;recommended in specific conditions&rdquo; and 3 identified &ldquo;highly discouraged&rdquo; tests. The results of the questionnaire are shown as mean (&plusmn;SD) of individual responses, thus allowing to define a scale of priority comprised between &ldquo;highly recommended&rdquo; and &ldquo;highly discouraged&rdquo;. Overall, 24 tests were classified as &ldquo;highly recommended&rdquo;, whereas 6 were &ldquo;highly discouraged&rdquo;. The remaining 16 tests were classified as &ldquo;somehow recommended&rdquo; or &ldquo;somehow discouraged&rdquo;. 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
Armonizzazione della diagnostica ematologica: lo stato della valutazione dei reticolociti
Harmonization in hematology: the status of reticulocyte count
E. Piva  |  S. Secchiero  |  F. Spolaore  |  F. Tosato  |  M. Plebani  | 
<p>Harmonization is a crucial step in laboratory&nbsp;medicine to provide reliable information. The reticulocyte count and even more maturity parameters and indices seem&nbsp;to be still highly variable, despite their proven clinical usefulness. Three hematology analyzers (Siemens Advia 2120,&nbsp;Sysmex XN-1000, Mindray BC-6800) were used to assess reticulocyte count (percentage and absolute count),&nbsp;parameters and indices of blood samples from 82 adult patients. Results from 92 participant laboratories to the last&nbsp;3 cycles (2012-2015) of EQA program of the Center of Biomedical Research were also evaluated. Statistical&nbsp;comparisons demonstrated an excellent correlation among the 3 instruments for reticulocyte count, both in&nbsp;percentage and absolute values. A systematic, not proportional difference in immature reticulocyte fraction results&nbsp;was observed between Advia 2120 and the other two analyzers, which conversely showed an excellent correlation&nbsp;between them. For the measurement of reticulocyte hemoglobin content, we found a systematic proportional&nbsp;difference between Advia 2120 and XN-1000, an excellent concordance between Advia 2120 and BC 6800 and a&nbsp;systematic not proportional difference between XN-1000 and BC 6800. Comparison between reticulocyte mean&nbsp;volume results obtained with Advia 2120 and BC 6800 showed a good correlation, even if systematic differences&nbsp;between the two methods were observed. For the reticulocyte counts the interlaboratory variability showed a CV&nbsp;Z10%, except for Advia 2120. EQA demonstrated the need of harmonization of reference intervals, which should go&nbsp;together with the harmonization of analytical methods for a correct clinical interpretation.</p>
Biochimica Clinica ; 40(3) 208-216
Contributi scientifici - Scientific Papers
Contenimento dei costi nel laboratorio clinico: razionamento o razionalizzazione?
Cost containment in clinical laboratories: rationing or rationalization?
M. Plebani  | 
<p>Although expenditures for laboratory tests&nbsp;represent a relatively small part of total healthcare costs, clinical laboratories have not been spared from cost&nbsp;containment projects. In particular, the indiscriminate use and overuse of laboratory testing contribute a significant&nbsp;and unnecessary burden on the healthcare system. Controlling laboratory testing should be based on four strategies:&nbsp;1) reducing reimbursement; 2) linking test demand to medical necessity; 3) active management of test utilization by&nbsp;laboratory staff; and 4) developing formularies and controlling expenditures. The first approach, based on the simple&nbsp;reduction of reimbursement, is effective in the short run, but presents several fundamental flaws. The second&nbsp;approach aims to decrease utilization of tests that are not medically necessary, for example eliminating duplicate&nbsp;orders for tests within specified time frames. The third approach ranges from simply having laboratory staff acting as&nbsp;gatekeeper, namely for specific test at high costs, to more systematic approaches. Finally, the fourth approach is&nbsp;similar to mechanisms used to guide appropriate drug utilization and control expenditures. All strategies present&nbsp;advantages and limitations and the optimal approach should require a combination of different options. Laboratory&nbsp;professionals are expert in monitoring test utilization and clinical laboratories are an important checkpoint in any&nbsp;control measures. Cost saving and waste avoidance represent an ethical duty to permit universal coverage and&nbsp;patient safety.</p>
Biochimica Clinica ; 40(2) 123-128
Opinioni - Opinions
L’iniziativa dei laboratori della Regione Veneto “Passaggio al Litro”
"Switching to the Liter": the initiative of laboratories in Veneto Region
Biochimica Clinica ; 40(2) 166-167
Lettere all'Editore - Letters to the Editor
Il laboratorio nella terapia anticoagulante orale
The role of laboratory medicine in monitoring oral anticoagulant therapy
A. Tosetto  |  S. Testa  |  W Ageno  |  C. Legnani  |  O. Paoletti  |  M. Plebani  |  D. Poli  |  D. Giavarina  | 
<p>The oral anticoagulant therapy is used&nbsp;in the prevention and treatment of venous and arterial thromboembolism in many different clinical settings. For this&nbsp;purpose, vitamin K antagonists (VKA), which indirectly reduce the activity of factors II, VII, IX and X preventing the&nbsp;vitamin K-mediated carboxylation of specific glutamic acid residues, and direct oral anticoagulants (DOAC), providing&nbsp;direct inhibition of thrombin (factor IIa) or factor Xa, are available. The VKA monitoring represents a daily challenge for&nbsp;clinical laboratories, due to the increasing number of patients, frequency of needed controls and the management&nbsp;complexity. Several solutions have been proposed to improve the management of patients treated by VKA, such as&nbsp;surveillance in dedicated clinics and use of portable monitors to allow patient self-testing and self-management.&nbsp;Although DOAC have been declared not requiring a standard laboratory monitoring, laboratory testing for measuring&nbsp;drug anticoagulant activity is however needed in many situations, such as in case of bleeding or thromboembolic&nbsp;complications, surgery or invasive procedures, suspected overdose and drug interactions, noncompliance or presence&nbsp;of renal or liver disease.</p>
Biochimica Clinica ; 40(1) 13-20
Rassegne - Reviews
Medicina personalizzata e laboratorio clinico: osare con cura
Personalized medicine and clinical laboratories: challenges and opportunities
M. Plebani  | 
<p>Personalized medicine is an&nbsp;emerging field with the goal of applying the concept of individual variability to determine the predisposition to disease,&nbsp;timely and accurate diagnoses and tailored therapeutic strategies. Laboratory medicine plays a key role in translating&nbsp;the concepts of personalized medicine into clinical practice. Following the sequencing of human genome, many new&nbsp;&ldquo;omics&rdquo; disciplines have emerged. These new disciplines are the key to the development of personalized medicine&nbsp;as they contribute to the understanding of disease at a molecular level and to the identification of new biomarkers as&nbsp;quantified parameters predictive to the development of a disease, its prognosis or clinical response, and as target for&nbsp;new treatments. A multiple approach integrating various technologies needs to be pursued and the implementation&nbsp;of new statistical methods and novel algorithms is required. Laboratory professionals have to assure not only the&nbsp;development of robust and accurate assays, but to promote harmonized procedures for sample collection, handling&nbsp;and storage. Finally, a closer interaction with clinicians should be provided as there is an increasing recognition of the&nbsp;need of clinical advice for an appropriate test request and result interpretation and utilization.</p>
Biochimica Clinica ; 40(1) 33-39
Opinioni - Opinions
Sindrome POEMS: “Hevylite” e “Freelite” a confronto
POEMS syndrome: Heavy Light Chains vs Free Light Chains measurements
<p>POEMS syndrome is a rare paraneoplastic, multisystemic, plasma cell discrasia characterized by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes. Most patients have high serum free light chains (sFLC) concentrations but a normal sFLC ratio. Hevylite (HLC) is a new method that allows separated quantification of the serum k and l bounded levels of the six isotype specific immunoglobulins. In this study HLC and sFLC were measured in serum samples during the follow up of two patients with POEMS syndrome. The HLC ratio of the involved monoclonal immunoglobulin could provide additional information to assess residual disease, allowing&nbsp; detection of relapse earlier than clinical symptoms in patients with POEMS syndrome.</p>
Biochimica Clinica ; 40(1) e1-e3
Casi clinici - Case report
Armonizzazione della notifica dei valori critici come contributo al miglioramento della sicurezza e della cura del paziente
Harmonization of the notification of critical values as contribution to the improvement of patient safety and care
<p>A project for harmonizing the notification of critical values was performed in our department, which covers 3&nbsp;different hospitals. We achieved the harmonization of definitions by distinguishing critical values, critical tests and&nbsp;abnormal results, according to the Joint Commission proposal. For critical tests, the requesting physicians should&nbsp;verify the availability of results as soon as possible, while the laboratory professionals must ensure appropriate and&nbsp;timely results. As an example, all requests from the Emergency Room are relevant and considered as critical tests,&nbsp;avoiding overload of alarms or calls, which distract the busy medical team. Identification of critical values was based&nbsp;on consensus, guidelines and clinicians&rsquo; opinion. The practice was harmonized by automated notification systems&nbsp;and by establishing who should report critical values on an established time frame to the responsible licensed&nbsp;caregiver, so that the patient can be promptly treated. Timeliness was linked with clinical effectiveness with the aim<br />to provide the best outcome at the lowest cost. Finally, harmonization was directed to develop quality indicators&nbsp;regarding the policies of critical value communication, the monitoring of the timeliness in reporting and the need to&nbsp;evaluate how the effectiveness of improved communication assures better clinical outcomes. The realization of&nbsp;harmonized critical value notification may support the clinical decision making, leading to an improvement in patient&nbsp;safety and care.</p>
Biochimica Clinica ; 39(6) 595-600
Contributi scientifici - Scientific Papers
Armonizzazione in Medicina di Laboratorio
Harmonization in Laboratory Medicine
Biochimica Clinica ; 39(6) 546-547
Editoriale - Editorial
Gli indicatori di qualità nel processo di armonizzazione in Medicina di Laboratorio
Harmonization of quality indicators in Laboratory Medicine
<p>According to the International Standard for medical&nbsp;laboratories accreditation ISO 15189:2012, the laboratory should establish and periodically review quality indicators&nbsp;(QIs) to monitor and evaluate performance throughout critical aspects of pre-, intra and post-analytical processes.&nbsp;The use of QIs is needed to provide information and accountability to users and to establish a program of continuous&nbsp;improvement to ensure the quality of care and patient safety. In this context, we designed a QIs system as a part of&nbsp;a coherent and integrated quality improvement strategy. The management of QIs is based on an internal assessment&nbsp;system (IAS), which allows us to evaluate our performance over time and on the participation in an interlaboratory&nbsp;comparison managed as an EQA program, in order to compare our performance with other laboratories. The IAS&nbsp;includes a list of QIs, a form describing the specifications of each QI and a standard operating procedure. We&nbsp;participated in the project developed by the Working Group &ldquo;Laboratory errors and patient safety&rdquo; of IFCC on QIs.&nbsp;The project aims to identify a model of QIs that can be used worldwide through an EQA program. This paper aims to&nbsp;stimulate harmonization initiatives concerning QIs on the basis of the method and results of described experience.</p>
Biochimica Clinica ; 39(6) 601-608
Contributi scientifici - Scientific Papers
Caso atipico di orticaria
A case of atypical urticaria
<p>Adult onset Still&rsquo;s disease (AOSD) is a rare clinical entity with unknown etiology and&nbsp;pathogenesis, characterized by high spiking fevers, arthritis, typical evanescent, nonpruritic, macular and salmon<br />coloured rash, and multiorgan involvement. AOSD remains a diagnostic challenge due to the overlapping features&nbsp;with numerous infective, neoplastic and rheumatological conditions. A case of AOSD with atypical cutaneous&nbsp;manifestations in a 50-year-old female is reported. The patient&rsquo;s symptoms included: remittent fever, widespread&nbsp;urticarial, maculopapular erythema and a sore throat. Hematological investigations showed leukocytosis with&nbsp;neutrophilia. There were markedly elevated levels of serum ferritin (20.920 &mu;g/L) and mild liver dysfunction. A&nbsp;glycosylated ferritin assay was performed because of a severe hyperferritinemia, showing a reduction of the&nbsp;glycosylated fraction (&lt;20%), a newly proposed diagnostic criteria for AOSD. We emphasize the diagnostic value of&nbsp;low glycosylated ferritin concentration for the differential diagnosis of this rare disease, particularly in case of atypical&nbsp;presentation.</p>
Biochimica Clinica ; 39(5) e10-e12
Casi clinici - Case report
Armonizzazione in laboratorio: verso una visione globale
Harmonization in Laboratory Medicine: towards a global vision
Biochimica Clinica ; 39(1) 012-014
Editoriale - Editorial
I laboratori clinici nell’emergenza dei focolai epidemici infettivi: Ebola e oltre
Clinical laboratories and infectious outbreak emergencies: Ebola and beyond
G. Lippi  |  C. Mattiuzzi  |  M. Plebani  | 
Biochimica Clinica ; 38(6) 604-606
Editoriale - Editorial
In ricordo di Lauro Galzigna
In memory of Lauro Galzigna
M. Plebani  | 
Biochimica Clinica ; 38(4) 352
Notizie SIBioC - SIBioC News
Emoglobinuria parossistica notturna
Paroxysmal nocturnal hemoglobinuria
<p>Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired&nbsp;hematological disease of the hematopoietic stem cell. PNH arises as a consequence of non-malignant clonal&nbsp;expansion of hematopoietic stem cells and progeny mature blood cells of both myeloid and monocyte lineage, which&nbsp;are deficient in some surface proteins, including the two complement regulators CD55 and CD59. As a result, PNH&nbsp;erythrocytes are incapable to modulate on their surface physiologic complement activation, leading to complement-mediated&nbsp;intravascular hemolysis, which is the central clinical feature of PNH. Diagnosis and monitoring of PNH&nbsp;clones currently rely on the analysis of CD59 expression on red blood cells and FLAER (fluorescent aerolysin) and&nbsp;some glycophosphatidylinositol-anchored proteins on granulocyte and monocyte lineages by flow cytometry. Despite&nbsp;the availability of safe and effective targeted therapy that controls intravascular hemolysis, the management of PNH&nbsp;remains difficult because of disease heterogeneity and close association with bone marrow failure syndromes.</p>
Biochimica Clinica ; 37(4) 268-274
Rassegne - Reviews
Note metodologiche sull’acquisizione e sull’uso dei sistemi chiusi sottovuoto per il prelievo, il trattamento e la conservazione dei campioni ematici venosi destinati alla diagnostica di laboratorio
Methodological notes on acquisition and use of close evacuated systems for collection, handling and storage of venous blood samples for laboratory diagnostics
M. Plebani  |  M. Caputo  |  D. Giavarina  |  G. Lippi  | 
<p>Evacuated systems for collection of venous blood&nbsp;are integrated systems of medical and in vitro diagnostic medical devices regulated under European Directives and&nbsp;Italian Legislative Decrees. Both Directives and Decrees endorse the requirement that the whole combination of&nbsp;devices, representing an integrated apparatus, must be safe and not impair the specific performance of each single&nbsp;device. According to mandatory requirements, manufacturers must ensure full compatibility between each component&nbsp;of the system, while the users are responsible for verifying the compatibility of different devices in order to avoid&nbsp;potential quality and safety problems. The acquisition of various devices from different manufacturers may lead to&nbsp;combinations that are not validated by manufacturers themselves and are thus expected to be validated and verified&nbsp;by the users to demonstrate that the system remains safe and will not impair the performance of the individual&nbsp;elements. Therefore, the possibility of purchasing different devices separately should be carefully weighted in terms&nbsp;of risk-benefit, taking into consideration the additional costs of the validation/verification process that should be&nbsp;carried out by the potential user. Since preanalytical problems are the major source of errors in the total testing&nbsp;process, the selection and acquisition of close evacuated systems for blood collection should be considered a critical&nbsp;issue for assuring quality, safety and efficiency of the preanalytical phase of laboratory diagnostics and, therefore, of&nbsp;the total testing process.</p>
Biochimica Clinica ; 37(4) 303-311
Documenti SIBioC - SIBioC Documents
Un caso di emoglobinuria parossistica notturna associata a mielodisplasia
A case of paroxysmal nocturnal hemoglobinuria in a patient with myelodysplasia
<p>Paroxysmal nocturnal&nbsp;hemoglobinuria (PNH) is a rare acquired hematological disease of the hematopoietic stem cell. PNH arises as a&nbsp;consequence of non-malignant clonal expansion of hematopoietic stem cells and progeny mature blood cells of both&nbsp;myeloid and monocyte lineage, which are deficient in some surface proteins, including the two complement regulators&nbsp;CD55 and CD59. As a result, PNH erythrocytes are incapable to modulate on their surface physiologic complement&nbsp;activation, leading to complement-mediated intravascular hemolysis, which is the central clinical feature of PNH. We&nbsp;present a case of a 16 years old Ukrainian boy who presented with a diagnosis of myelodysplastic syndrome and&nbsp;who was found to be affected by PNH.</p>
Biochimica Clinica ; 37(4) 326-328
Casi clinici - Case Report
Necessità di una descrizione completa dei metodi di laboratorio e del trattamento del campione nella pubblicazione di studi clinici: un appello agli editori di riviste mediche
An appeal to medical journal editors: the need for a full description of laboratory methods and specimen handling in clinical study reports.
N. Rifai  |  T.M. Annesley  |  J.P. Berg  |  C. Brugnara  |  E. Delvin  |  E.J. Lamb  |  P.M. Ness  |  M. Plebani  |  M.R. Wick  |  A. Wu  |  J. Delanghe  | 
<p>As editors of the laboratory medicine journals we urge the medical journal editors to adopt and enforce the following requirements for clinical studies that include laboratory testing for biomarkers: 1) for commercial diagnostic tests, authors must include the actual name and generation of assay, the manufacturer and the instrument used for analyses; 2) authors must report performance characteristics, such as the imprecision of the assay in the investigators&#8217; laboratories, the assay&#8217;s reportable range, and any reference interval used in the study; 3) authors must clearly indicate the types of specimens analyzed and the storage conditions for these specimens.</p>
Biochimica Clinica ; 36(3) 193-195
Opinioni - Opinions
Una rilettura di “Funzione e compiti del laboratorio nell’ospedale moderno” a 40 anni di distanza
Re-reading the Ceriotti’s paper 40 years later
M. Plebani  | 
<p>In 1972, the opening lecture of the SIBioC Congress by Giovanni Ceriotti and Carlo Riga recognized two main missions of the clinical laboratory: its role in assuring a valuable diagnostic-therapeutic process and the need to improve the scientific knowledge for achieving a more effective clinical practice. In the same document, the Authors identified the main duties of laboratory professionals, ranging from the choice of analytical methods and their automation to the clinical advice on test request and result interpretation. In the same year, George Lundberg described the &#8220;brain-to-brain loop&#8221; concept that basically identified all pre-, intra- and post-analytical steps of the total testing process, stressing the need of assuring quality and safety in every step for finally achieving satisfactory clinical outcomes. The changing face of clinical laboratories due to the impressive advancement in analytical techniques, automation and informatics has led to a dramatic switch of the role and duties of laboratory professionals from diagnostic operators to designers of diagnostic operations. However, it is still debatable how laboratorians may better translate into clinical practice the innovation due to technological and scientific developments to assure a more visible and reliable appreciation of their role in the modern healthcare system.</p>
Biochimica Clinica ; 36(1) 33-35
Opinioni - Opinions
Identificazione di potenziali biomarcatori sierici di adenocarcinoma pancreatico
Identification of potential serum biomarkers of pancreatic cancer
A. Padoan  |  P. Fogar  |  E. Greco  |  E. Fadi  |  D. Bozzato  |  S. Moz  |  F. Navaglia  |  C.F. Zambon  |  R. Seraglia  |  M. Pelloso  |  A. Rossi  |  M. Plebani  | 
Biochimica Clinica ; 35(4) 280
Valore prognostico della determinazione di MR-proadrenomedullina e copeptina nello scompenso cardiaco cronico
MR-proadrenomedullin and copeptin: prognostic role in chronic heart failure
M.M. Mion  |  M. Zaninotto  |  B. Boffa  |  F. Tona  |  G. Masiero  |  F. Calabrò  |  S. Iliceto  |  M. Plebani  | 
Biochimica Clinica ; 35(3) 193
Linee guida per la gestione dei programmi di Valutazione Esterna di Qualità
Guidelines for External Quality Assessment Scheme organization
Biochimica Clinica ; 35(2) 107
Point-of-care testing - Needs, Opportunity, and innovation (3rd edition)
Point-of-care testing - Needs, Opportunity, and innovation (3rd edition)
M. Plebani  | 
Biochimica Clinica ; 35(1) 62
La Medicina di Laboratorio: gli specialisti di domani
Laboratory Medicine: specialists of tomorrow
<p>Laboratory Medicine rides the wave of technological progress, themetamorphosis of information systems and data management. The Young Specialist is not a mere observer, butrather takes a leading role in this change, taking advantage of the opportunities offered by &ldquo;omics&rdquo; technologies,capturing new ideas and innovative stimuli that lead to a new concept of work and research oriented to health andprevention. Thanks to the support of international web platforms, training and exchange programs supported by theInternational Scientific Societies and Federations that favor professional and scientific growth, Young Scientists workin a global context. In this scenario, the SIBioC Young Scientists Study Group, with the auspices of SIBioC, EFLMand IFCC, organized a meeting on &quot;Laboratory Medicine: Specialists of tomorrow&quot; with the aim of discussing andhighlighting some of the most important challenges, such as technological progress, training and internationalizationof young people. Finally, the future of laboratory medicine looks at a multidisciplinary approach that leads tointegrated diagnosis, identification of the frail patient, the use of the Point of Care Testing as an indispensable tool incrisis areas, making the dialogue between physician and laboratory specialist a fundamental step for the diagnosisand treatment with the final aim of a better outcome for the patient.</p>
Biochimica Clinica ; 17(1)
Documenti - Documents
Patologie cardiovascolari e troponine cardiache: la storia di un legame indissolubile
Cardiovascular diseases and cardiac troponins: the history of a lasting connection
<p>The evolution of thebiochemical diagnosis of cardiac diseases, represents a paradigm of the laboratory medicine evolution in the recent years.<br />Starting from the use of poor specific and sensitive biomarkers, the &ldquo;so-called&rdquo; cardiac enzymes (aspartateaminotransferase; lactate dehydrogenase; creatine kinase) recommended by World Health Organization for the acutemyocardial infarction (AMI) diagnosis, a fundamental development in biochemical knowledge has been obtained,providing new biomarkers (CK-MB, myoglobin) for a more specific and early diagnosis according to the clinical andtherapeutic needs. However, the revolutionary biochemical issue has been represented by the discovery of cardiactroponins and by the implementation of methods allowing their measurement in emergency setting in patients withacute chest pain. Cardiac troponins, are characterized by an absolute cardiac specificity and by a high sensitivity thatallow to carry out a timely and safe diagnosis of AMI, being recognized as &ldquo;gold standard&rdquo; in all clinical andbiochemical guidelines. In patients with acute chest pain and in ischemic clinical setting, a typical kinetic release ofbiomarker concentration may be suggestive of AMI even if ECG typical patterns are lacking. The actual improvementin analytical performance of troponins methods, particularly in the analytical sensitivity, allows to extend themeasurement also in diagnosis of minor myocardial damage in patients suffering from different cardiac disease, tomonitor the efficacy of therapy, the progression of the disease and to provide prognostic information and risk-stratification in addition to the clinical pathway.</p>
Biochimica Clinica ; 17(1)
Opinioni - Opinions
Pazienti diabetici di tipo 2, non in terapia insulinica e albumina glicata: una valutazione multidimensionale
Insuline-Naive type 2 diabetic patients: a multidimensional evaluation on the role of glycated albumin
<p>Insuline-Naa&iuml;ve type 2 diabetic patients: a multidimensional evaluation on the role of glycated albuminIntroduction: glycated Albumin (GA) is an innovative glycemic marker, that could be used in the clinical practice, asan add-on strategy, to the traditional glycemic monitoring systems, such as glycated haemoglobin (Hb1Ac) and fastingplasma glucose (FPG). The study aims at presenting the results of a multidimensional analysis conducted in Italy,exploring the main clinical, economic, ethical, social and organizational implications, related to the introduction of GA.Methods: an Health Technology Assessment (HTA) approach was implemented. The analysis considered the ItalianNational Healthcare Service (NHS) perspective, and assumed a 12-month time horizon, focusing on type 2 diabetespatients insulin-na&iuml;ve, assuming oral therapy. The 9 HTA dimensions (derived from the Core Model developed by theEuropean Network of HTA &ndash; EUnetHTA) were deployed, considering scientific evidence, health economics tools andqualitative approaches, through the administration of specific questionnaires to 15 diabetes experts.Results: literature reported better GA safety and efficacy profiles, thus being a predictor of the relative risk for diabetescomplications development, and increasing the therapeutic success after 3 months of therapy (97.0% versus71.6%).From an economic point of view, GA introduction resulted in an economic advantage of 1.06% and in a better trade-off between costs sustained and efficacy gained. Considering a 7-item Likert Scale (ranging from -3 to +3), negativeperceptions emerged with regard to equity aspects (0.13 versus0.72) due to GA limited accessibility, whereas it wouldimprove both patients (2.17 versus1.33) and care givers (1.50 versus0.83) quality of life. In the short term, GArequired training courses and equipment update, whereas, in the long term, it could be considered the preferablesolution from an organizational perspective (0.30 versus0.01).Conclusions: the results of this study demonstrated GA strategic relevance, its economic sustainability and feasibility,as well as the potential clinical pathway improvement.</p>
Biochimica Clinica ; 17(1)
Contributi Scientifici - Scientific Papers