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The report of the medical laboratory is the final result of the complex analytical activity that requires technology, automation, organization and competence. The content of the report has been defined since 2015, but the application of the legislative requirements is still incomplete. The need for interoperability of the medical laboratory reports in order to be easily accessible and understandable throughout Europe, increases the requirements for the development of standards for reporting of test names, units of measurement, qualitative expressions. The adoption of LOINC codes may improve interoperability, but the codes have to be used correctly and a stewardship from Scientific Societies is needed. The laboratory reports are moving from paper to electronic format, and this should help the readability and simplicity favoring the interpretation, but the increasing amount of data and information may make them more difficult to read. This aspect together with the rapid development of new analytical technologies increases the need for interpretative comments, that should be clear, avoid acronyms or excessive technical terms and tackle the real relevant aspects. Being the final product of our activity, the report deserves more attention from our profession. [ABSTRACT FROM AUTHOR]

Introduction: the increase of Mean Corpuscolar Hemoglobin Concentration (MCHC) in the Complete Blood Count (CBC) test is a complex issue, deserving great attention. Erytrocytes (RBC) count by impedance and the photometric hemoglobin (HGB) measurement can be influenced by both biological variables (cold agglutinins, lipemia, icterus, hemolysis, RBC alterations) and pre-analytical factors (collection, storage and transport of the sample). In this paper, the Complete Blood Count-Optical (CBC-O) algorithm is evaluated for the identification of the cause of the MCHC increase and for the suggested corrective action to correctly report the CBC parameters. Methods: 255 samples, collected with K2-EDTA anticoagulant, for the CBC test were used. The algorithm was triggered after the reticulocytes reflex testing (XN-RET) using the XN hematology analyzer (Sysmex), when MCHC was >365 g/L. The CBC-O tool uses a number of RBC and HGB measures and indices. Results: the samples were classified by the CBC-O algorithm into 5 groups according to the causes of the MCHC increase: cold agglutinins (n=70), cold agglutinins and HGB interferences (n=10), HGB interferences (n=6), RBC pathologies or hemolysis (n=32) and unclear situations with normal RBC profile (n=137). Discussion: MCHC elevation is a rare occurrence in routine daily practice, but it needs to be managed properly. The CBC-O algorithm is a useful tool since, in a short time, it allows to give indications on the probable causes of the increase and to report correct erythrocyte indices, without the need to treat the sample, which would otherwise lengthen the turn around time. [ABSTRACT FROM AUTHOR]

Introduction: in spite of the introduction of automated systems for urine sediment analysis, microscopy examination remains the gold standard. External Quality Assessment (EQA) programs on urine sediment are rare. This paper provides an analysis of results from 2012 to date of the EQA Italian program (Centro di Ricerca Biomedica, Regione Veneto) which involves today 255 laboratories. Methods: the EQA program includes four surveys/year. Participants are asked to identify and provide the clinical association of the presence of specific particles (2 surveys) and formulate the diagnosis of clinical cases presented (2 surveys). In 11 years, 202 images were proposed: 64 cells (9 types), 10 lipids (4 types), 59 casts (16 types), 36 crystals (13 types), 14 microorganisms (5 types), 19 contaminants (8 types) and 22 clinical cases were presented. Results: the correct identification rate (median; interquartiles) was very high for micro organisms (96.4; 91.9-99.9); high for crystals (92.2; 80.2-96.3) and lipids (91.1; 90.5-93.6); followed by casts (87.7; 80.1-91.8); contaminants (87.3; 77.2-96.0) and cells (82.8; 74.4-91.3). For clinical associations, the rate of correct answers was 96.5 (range 48.7- 100%). For clinical cases, due to the overall rate of particle misidentification throughout surveys, only 58.6% (44.9- 68.8%) of participants achieved access to clinical diagnosis. Of these, 92,0% (78.1-95.5%) were able to indicate the correct diagnosis. Conclusions: the program can be used as a tool to improve the identification of urine particles and the knowledge of their clinical significance and to encourage specialists of laboratory medicine to correlate urine findings with other laboratory data and the clinical history of the patient, an aspect that improves the value of the day by day work. [ABSTRACT FROM AUTHOR]

The term "laboratory stewardship" refers to the proper ordering and evaluation of laboratory tests. The inappropriateness of the request is not only the overuse of laboratory tests, ordering low-value tests that have no impact on patient outcomes, but also the underuse of tests that would be necessary for the patient. In addition, the large number of tests offered by the laboratory, sometimes highly specialized, can cause difficult or incomplete interpretation of results. Accordingly, errors in requesting and interpreting results can lead from suboptimal patient management to very negative consequences for the patient. Communication and collaboration between clinicians and laboratory specialists can be an important tool in providing the right test, for the right patient, at the right time as well as the right interpretation and use. In this opinion paper, we propose a strategic plan aimed at strengthening the biunivocal clinical-laboratory interaction with the ultimate goal of improving the quality of patient care and reducing costs for both patients and the health care system. [ABSTRACT FROM AUTHOR]

Urine albumin is a well-known biomarker of proven clinical utility for relevant pathological conditions and a risk factor for cardiovascular mortality. This paper is aimed to illustrate the state-of-art of albuminuria measurement and the adherence to the official recommendations in scientific writing. In spite of the urine albumin clinical importance, the standardisation of the analyte is not completed yet, but the adoption of decisional values (established in 2013) would require standardized methods to allow the correct classification of patients. The Italian EQA scheme for albuminuria shows variable bias to the consensus value, depending on the analytical system: a typical situation originating from the lack of international standardisation. The harmonisation of the measure is more advanced: the EQA data show that 74% of participants use the albumin/creatinine ratio to report the urine albumin excretion. A recent systematic review examined how the albuminuria data are reported in clinical studies. A sub-optimal situation is illustrated: the laboratory information is often lacking or incorrectly reported. The obsolete term "microalbuminuria" is used in >40% of the studies, only 20% of the studies uses the correct sample (first morning void). The data about the post-analytical are more encouraging: the measurement units and the decisional values are correctly reported in the majority of the studies. The correction of this situation, that makes it difficult to transfer the results from clinical studies to the daily practice, requires a stringent collaboration between laboratory professionals and clinicians: working together in multidisciplinary groups to understand the respective needs is to be promoted. [ABSTRACT FROM AUTHOR]

The protein concentration in urine is a valuable parameter in assessing kidney function. Usually, blood proteins do not pass through the renal filter in healthy subjects; proteinuria, which can sometimes be detected as a simple, occasional laboratory finding, is a relatively common condition of which those affected are unaware. Epidemiologically, it is a condition that involves almost 10% of the population worldwide. The mechanisms underlying the release of proteins by the kidneys are different: a newly detected proteinuria may precede the onset of renal disease or systemic diseases, and the physician must appropriately evaluate it. This paper provides a hint of epidemiology, some notes of pathophysiology, an overview of the types of proteinuria, a rundown on laboratory techniques and a brief, certainly not exhaustive, review of some non-oncological pathologies associated with proteinuria. The aim is to show the extent to which proteinuria can play a decisive role in the patient's overall assessment. The urine protein test, a basic, non-invasive test, easy to perform by any laboratory, even the most poorly equipped, is a fundamental indicator of a subject's health status in combination with other markers. Thus, it confirms once again the crucial role of the laboratory in providing the physician with necessary diagnostic and prognostic data that is easy to perform, inexpensive and yet of great benefit for the patient management. [ABSTRACT FROM AUTHOR]

Catecholamines are produced by the sympathetic nervous system or by the medullary adrenal glands and play a key role both as hormones and as neurotransmitters. An increase in their production can lead to hypertension, due to neuroendocrine tumors like pheochromocytoma, paraganglioma and neuroblastoma. Among tumors of neuroendocrine derivation, there are also carcinoids that can cause carcinoid syndrome, associated with an excess of serotonin release. Proper biochemical analysis of patients suffering from these tumors is crucial to confirm the presence of excess production of catecholamines or serotonin and their metabolites. Serious and life-threatening cardiovascular complications related to cathecolamines and their metabolites pose a challenge to the laboratory for a timely and accurate diagnosis of neuroendocrine tumors. The application of innovative technologies to determine these analytes, such as LC-MS/MS, potentially associated with a metabolomic approach, may provide an efficient tool to help physicians recognizing and appropriately treating these still difficult-to-find clinical entities. As a complement to this paper, we present a personal experience about the analysis of biogenic amines and their metabolites performed on both 24-hour and spot urines. The LC-MS/MS method is used with three different preparation phases: total metanephrines (free and conjugate), catecholamines, free methanephrine and serotonin and vanillylmandelic acid (VMA), homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA). The organization of the chromatography and mass spectrometry division, based on expert technicians, includes centralized acceptance of samples, automation of the preparation phase and middleware-based validation of the results, offering to clinicians a valuable help in this challenging diagnostic. [ABSTRACT FROM AUTHOR]

The pathogenesis of urolithiasis is related to the presence of physico-chemical abnormalities in the urine environment. These anomalies can be highlighted and evaluated through specific biochemical investigations, often not included in the usual activities of a hospital laboratory. The laboratory activities include the adoption of the most appropriate procedures for the evaluation of urine saturation with respect to lithogenic salts (propensity to stone formation), the identification and analysis of precursors and inhibitors of crystallization, the biochemical investigation for the identification of pre-existing diseases, including the genetic ones, and the analysis of kidney stones. Over the years, in the medical approach to nephrolithiasis, the need for specialized analytical techniques has increasingly raised, requiring the use of versatile technology (HPLC, GC-LC/MS, FTIR), adaptable to the investigation of substances belonging to the most varied classes and present in different biological matrices. In this paper we describe the main analytical activities carried out by a specialized laboratory for the study of renal stone disease. [ABSTRACT FROM AUTHOR]

Primary hyperoxalurias (PH) are autosomal recessive metabolic disorders, characterised by overproduction and urinary excretion of oxalate, presenting with nephrolithiasis, nephrocalcinosis and kidney failure. Plasma oxalate is higher than normal in PH, and it rises further in renal failure. When glomerular filtration rate falls below 30 mL/min /1.73m2, oxalate levels increase sharply and plasma becomes supersaturated with calcium oxalate, which precipitates in body tissues (systemic oxalosis). Three types of PH are described; the most frequent is PH1 (70-80%), due to deficiency of L-alanine:glyoxylate aminotransferase (AGT), the enzyme which catalyses in hepatocytes the transamination of alanine and glyoxylate to pyruvate and glycine. That leads to accumulation of glyoxylate, which is converted both in oxalate (by lactate dehydrogenase, LDH) and glycolate (by glyoxylate reductase). Increased levels of glycolate, both in serum and urine, are the hallmark of PH1. PH2 is due to variants of gene encoding for the enzyme glyoxylate and hydroxypyruvate reductase (GRHPR), which converts both glyoxylate to glycolate and hydroxypiruvate to D-glycerate in many tissues. Pathologic variants of GRHPR gene induce increased levels of glyoxylate and hydroxypyruvate, converted by LDH to oxalate and L-glycerate respectively. High levels of glycerate, both in serum and urine, allow the metabolic diagnosis of PH2. PH3 is due to variants of HOGA gene, which catalyses the cleavage of 4-hydroxy-2- oxoglutarate (HOG) to pyruvate and glyoxylate. Increased levels of both HOG and 4-hydroxy glutamate are metabolic hallmark of PH3. In this paper, an overview of oxalate metabolism was reported, and the main features of the pathophysiology, diagnosis, clinical course and treatment of PH as well. [ABSTRACT FROM AUTHOR]

Indirect methods are data mining techniques for establishing or verifying reference intervals. They present many advantages over the traditional direct approach, including reduced costs, closeness of preanalytical and analytical conditions to routine conditions and usefulness in specific age groups or with uncommon sample types. After discussing advantages and limitations of the indirect approach, in this paper the main statistical algorithms, and their implementation in open-source software as well, are briefly introduced by a practical example. Moreover, key aspects of data selection and preparation are discussed. The indirect methods represent a powerful and valuable approach for the definition or validation of reference intervals, whose knowledge and correct use should be part of the laboratorian's toolbox. [ABSTRACT FROM AUTHOR]

Introduction: kappa index (ratio between cerebrospinal fluid (CSF)/serum kappa free light chains and CSF/serum albumin) is an emerging CSF biomarker, easily and quickly evaluable using a complete automatic technique that offers a quantitative result, to integrate the qualitative assessment of oligoclonal bands (OCB). These parameters can be further supplemented with the central vein sign (CVS), an imaging parameter indicative of inflammatory injury in the white matter in patients with Multiple Sclerosis (MS). Methods: we analyzed CSF biomarkers, OCB and kappa index in patients who underwent on CSF examination in our MS Center in Firenze (Italy) during 2020-2022. The patients were divided in MS and not MS (nMS) groups and further divided in OCB+ or OCB-, kappa index+ or kappa index-, and CVS+ or CVS-patients. Results: the study population is composed by 114 patients (77 women and 37 men) with an average age of 42.2 years. Among the 114 participants, 68 (59.6%) were MS and 46 (40.4%) nMS. We also analyzed a subgroup of 49 patients with 3T Magnetic Resonance (n=31 MS and n=18 nMS). When the kappa index was compared between the two groups, it showed higher sensitivity, Positive Predictive Value and Negative Predictive Value than OCB; the combination of CVS and kappa index showed the best ratio of sensitivity to specificity compared with the other groups analyzed. Discussion: these results also suggest that kappa index can be used as a screening test in MS even before performing OCB, in a reflex approach that can improve MS diagnosis. Using both MRI and CSF biomarkers ameliorate remarkably the MS diagnosis. [ABSTRACT FROM AUTHOR]

Introduction: the use of antioxidant supplements in athletes is frequent but rarely the choice is based on preliminary biochemical tests. Aim of our work was to verify the usefulness of some blood and urinary markers of oxidative and inflammatory balance in a case of antioxidant supplementation involving athletes of an elite women's football team. Methods: in preparation for an increased workload, 22 players took a food supplement containing N-acetylcysteine (NAC) for 30 days. At the beginning and at the end of this period, some biomarkers of muscle physiology, inflammation, redox balance and oxidative damage were measured. Results: after supplementation, total antioxidant barrier remained unchanged and anti-inflammatory capacity increased despite the higher workload. However, the measurement of oxidative damage markers did not allow us to reach useful conclusions. Discussion: redox balance, glutathione, IL-6 and IL-10 measurements before supplementation showed an initial oxidative-inflammatory balance, and have proven useful for evaluating the effects of the antioxidant treatment. The maintenance of oxidative balance and the increase in anti-inflammatory capacity seem to indicate its effectiveness. Unfortunately, the lack of a control group prevented us from attributing the beneficial effects to the treatment alone. Supplementation with antioxidants in sport should be a thoughtful choice based on a preliminar assessment of the athlete's real needs. The role of the laboratory is crucial to evaluate the oxidative balance of athletes, to plan the integration and subsequently to measure the effects of supplementation. [ABSTRACT FROM AUTHOR]

Introduction: the analysis of cerebrospinal fluid (CSF) and the determination of free light chains (FLC) are routinely used in the clinical laboratory. We investigated the utility of kappa index (Qkappa FLC/Qalb) as a specific biomarker for the differential diagnosis of multiple sclerosis and inflammatory neurological disorders in a pediatric population. Methods: among 978 patients enrolled from January 2019 to May 2022, we analyzed 53 pediatric samples (0-17 years old). Albumin, IgG and kappa FLC in serum and CSF were measured by turbidimetric method, while isoelectrofocusing was performed to check for the presence of oligoclonal bands. The related CSF/serum indices (kappa index and IgG index) are also calculated. Results: according to the clinical diagnosis, four groups of patients have been identified: multiple sclerosis, inflammatory neurological disorders, non-inflammatory diseases, negative controls. The kappa index cut-off of 6.2, obtained from our previous study, yielded 83.3% sensitivity and 85.7% specificity in the comparison between multiple sclerosis patients and the other groups. The IgG index (showing 50% sensitivity and 45.5% specificity at a threshold of 0.50) confirmed its poor diagnostic performance. In the comparison between inflammatory and non-inflammatory disorders a kappa index cut-off of 3.3 was associated with 80.6% sensitivity and 76.5% specificity. Conclusion: the kappa index cut off (6.2) in use in our laboratory for multiple sclerosis diagnosis in the adult population can be confirmed in a pediatric cohort. Moreover, a lower kappa index cut-off (3.3) seems useful to discriminate pediatric inflammatory diseases, as recently reported by other Authors, and can be applied in the differential diagnosis of inflammatory processes of the central nervous system. [ABSTRACT FROM AUTHOR]

Background: the poor adherence to guidelines approved by scientific societies are widely described as a possible cause of criticisms in the management of several diseases. In the setting of dyslipidemia, a lack of compliance with clinical and biochemical recommendations defining the informations that should be included in the laboratory report, could be a relevant issue. Methods: in order to verify the state-of-the art of this specific topic, a survey containing 8 questions spanning from the pre-analitycal phase (panel of tests, nonfasting testing), to analytical (types of methods and equations) and to post-analytical phase (reference interval, desirable values, therapeutic goals) was sent to the laboratory professionals registered in the Italian Society of Clinical Biochemistry and Molecular Biology (SIBioC). Results: the most interesting results demonstrate that: about 40% of the laboratories add to the traditional lipid panels (total, LDL and HDL cholesterol, tryglicerides) the recommended measurement of apolipoproteins (Apo-A1, Apo-B and Lpa); 89% adopt the fasting testing; 73.6% use direct methods to measure HDL-C and 29% calculate LDL-C using Friedewald equation; 87.3% of the values are reported using the traditional (mg/dL) units; 64.5% use the reference interval as comparator, inadequate for the most part of lipid tests, 51.4% desirable levels, only 5.61% the recommended therapeutic goals. Discussion: on the basis of the obtained data, a shared improvement in the adoption and application of the recommendations published by SIBioC but poorly adopted until now, seems to be a fundamental activity that should be undertaken in the near future. [ABSTRACT FROM AUTHOR]

Introduction: this study was designed to measure ethyl alcohol concentrations in blood samples of different matrices (Li-He plasma, K2-EDTA plasma and serum) with the DRI® method on the ILab Taurus analyzer. The aim of the protocol was to compare the values between the matrices K2-EDTA and serum with Li-He plasma. Furthermore, 18 real samples from the emergency room were used to compare the results obtained with the enzymatic method on both Li-He and K2-EDTA plasma in comparison with the GC/HS reference method. Methods: serum, Li-He and K2-EDTA samples were obtained from left-over routine samples to obtain different pools (serum, Li-He plasma and K2-EDTA plasma pools). Samples with different expected concentrations of ethanol (range 0.00-2.22 g/L) were prepared in situ (60 samples for each matrix) by precise additions of a 10% ethanol solution. All these samples were stored at -20°C until use. Results: in the expected concentration range between 0.42 and 0.85 g/L and around 0.8 and 1.5 g/L [which incorporates most of the legally permitted levels of BAC (Blood Alcohol Concentration) in Europe including Italy] the CV% obtained are all <5.0%. The GC/HS correlation with ILab Taurus for both plasma matrices, LI-He and K2-EDTA evaluated in 18 genuine samples was excellent. Discussion: all the obtained results show that for all the matrices evaluated in the study, the analytical performances are highly satisfactory. [ABSTRACT FROM AUTHOR]

The revolutionary new cystic fibrosis (CF) drug combination of ivacaftor (IVA), tezacaftor (TEZ) and elexacaftor (ELX) directly modulates the activity and trafficking of the transmembrane conductance defect (CFTR) regulatory protein underlying CF disease. Limited information is currently available in the literature on plasmatic concentrations of IVA, TEZ and ELX. However, significant interindividual pharmacokinetic variability has been reported in patients receiving the IVA/TEZ/ELX combination, exacerbated by several previously documented drug-drug interactions. Therapeutic drug monitoring (TDM) could therefore be useful in optimizing treatments with CFTR modulators. The purpose of this paper is to provide an overview of currently available information on pharmacokinetics/pharmacodynamics (PK/PD) of the drugs and their relationships to better understand the basis for differences in treatment response. Relevant articles reporting PK/PD data on IVA, TEZ, ELX administered for the treatment of CF were obtained from the PubMed database. [ABSTRACT FROM AUTHOR]

The recent position paper by the European Federation of Laboratory Medicine (EFLM) advises against following the US recommendations on the use of the new race-free version of the Chronic Kidney Disease-Epidemiology Consortium (CKD-EPI 2021) equation to estimate the glomerular filtration rate (eGFR). The main concern derives from a possible poor CKD estimation, causing an underestimation of renal impairment for the Caucasian population, and therefore for all Europeans. Considering the relevance of the EFLM indication, Biochimica Clinica published the Italian translation of the document and an accompanying editorial suggesting that the European position could be an end point for a better eGFR harmonization. However, the use of different equations for eGFR in US and Europe will entail rather a worse harmonisation: the eGFR values are used for patients enrolment in numerous clinical studies, for the admission to diagnostic procedures or therapies and for the evaluation of their complications and adverse effects. As a consequence, many clinical trials will not be comparable, guidelines and recommendations will be less easily transferable from one country to another and the "regionality" of the equations will not slow down the search for new equations, for different groups and different countries. With equally shared responsibility between US and Europe, this situation seems to be a paradigmatic example of how recommendations in laboratory medicine should not be developed. Nevertheless, the EFLM indication not to adopt the CKD-EPI 2021 race-free equation should be accepted for the moment in Europe, since the harmonization between neighbouring and regional sanitary structures is a priority in the patient care. It should be strengthened that the problem has not been solved yet, and that a greater harmonization action must be rapidly sought, with the aim of a homogeneous calculation and reporting of this widely diffused estimate. [ABSTRACT FROM AUTHOR]

Introduction: monoclonal antibodies therapeutic (t-mAbs) are used in the treatment of multiple myeloma (MM). They are composed of IgG-k and may interfere with the patient's endogenous IgG-k monoclonal component (MC). The Hydrashift test (Sebia, Lisses, FR), the daratumumab immunofixation reflex test (DIRA test), is able to eliminate interference by t-mAbs. This work aims to determine how many DIRA tests were performed in the laboratory of the Department of Laboratory Medicine of Modena (Italy) and how the DIRA test has been used in our daily practice and its impact on the clinical management of the patient as well. Methods: the DIRA test was applied by the laboratory on patients selected on the basis of: their clinical history, of monoclonal components, comparison with previous electrophoresis, the characteristic pattern of the gamma zone, and evidence of an additional peak in the gamma zone. The data were extracted from the laboratory information system. Results: from August 2021 to December 2022 we performed the DIRA test on 240 samples for a total of 160 patients. 198 (82.5%) samples came from onco-haematological wards or day hospitals, the remaining 17.5% included samples from external sampling centers or non-onco-haematological. In 88 (55%) patients the DIRA test was positive. Conclusions: the use of the DIRA test allowed a correct diagnosis in 55% of the patients undergoing electrophoretic examination. DIRA is an inexpensive test, easily performed in any laboratory; however, an effective use of the test requires a close collaboration between haematologists and the laboratory. [ABSTRACT FROM AUTHOR]

Introduction: nephrolithiasis is one of the most frequent urologic diseases and the determination of molecular composition and the quantification of stone components are helpful to establish the etiology of urinary stone disease, with important clinical implications for the management of these patients. Stone analysis plays a valuable role in the diagnosis of kidney stone disease, specifically in uncommon kidney stones such as uric acid, cystine, infectioninduced and drug-induced stones. Methods: among the many different methods available for urinary stone analysis, the Fourier-trasform infrared spettroscopy (FT-IR) is one the most reliable method providing unambiguous information about stone composition. In the Padova laboratory is routinely used ThermoFisher Nicolet IS5, a infrared spettroscopy instrumentation that emits a beam of infrared light through the sample, which interacts with the molecules in the sample producing a spectrum which is compared with a library. From January 2016 to December 2021 we analyzed 9265 urinary stones with FT-IR. Results: 55% of stones were made of calcium oxalate, followed by uric acid stones (14%) and calcium phosphate (10.3%); inflammatory stones, mixed stones and cystine stones have been found in variable quantities. Conclusions: stone analysis provides valuable information about the cause and risk factors and can help in identifying the type of stone, which is important for determining the underlying metabolic disorder and for monitoring the effectiveness of treatment. Therefore, urinary stone analysis is an essential part of the evaluation and management of patients with kidney stone disease. [ABSTRACT FROM AUTHOR]

Introduction: the Coordination Regional Center for Laboratory Medicine of Lombardy Region provides the External Quality Assessment (EQA) scheme of urine particle evaluation with the aim to verify the inter-laboratory reproducibility of the morphological identification of urine particles. In 2022 we evaluated the concordance between the results obtained testing the same images proposed in two different exercises. Methods: the EQA material consisted of digitalized images of two urine sediments (Case 1 and Case 2) in phase contrast microscopy, where the recognition of the most relevant elements (maximun 4) and the correlation to a clinical condition were requested. To each correct recognition a score of 1 was assigned. Results: in the image of Case 1 leukocytes, bacteria, isomorphic red blood cells and aggregated leukocytes, the typical elements of a urinary tract infection, were recognizable. In the image of Case 2 leukocytes, dysmorphic red blood cells and acanthocytes, the typical elements in a haematuria condition in glomerulonephritis, were recognizable. The percentage of recognition incresead from the first to the second exercise in both the Cases, although few laboratories obtained a full score and many laboratories did not recognized the most common elements frequently present in a urine sediment. Discussion: this EQA scheme was very helpful to verify and strengthen basic skills for the recognition of urinary sediment particles in order to support the clinical decision-making process, although there is some work to be done in order to improve the skills of the operators and the culture of quality in this specific field of laboratory medicine. [ABSTRACT FROM AUTHOR]

Introduction: to evaluate the qualitative test performance and inter-assay variations of SARS-CoV-2 nucleic acid detection tests by analysing the results of the External Quality Assessment (EQA) programme carried out in Lombardy in 2021. Methods: the 2021 EQA for SARS-CoV-2 molecular test programme consisted on testing of 12 exercise (12 samples of cells culture supernatants): 5 were SARS-CoV-2-negative and 7 SARS-CoV-2-positive samples [3 had viral load (VL) >5x10³ copies/mL, 4 VL=1-5x10³ copies/mL]. Participating laboratories provided qualitative (positive/negative) and quantitative (Cycle threshold, Ct value) results for each molecular test in use. Qualitative test performance was evaluated by positive/negative percent agreement (PPA/NPA); inter-assay variation of quantitative results was evaluated by coefficient of variation (CV). Results: 79 to 90 laboratories participated by using 199 to 231 systems, returning 2 623 qualitative/quantitative results. PPA ranged between 99.5% and 100%, NPA between 69.9% and 100%. NPA range was 99.1-100% by ruling out the "invalid" results (n=89). CV ranged between 11.6% and 13.5% (samples with VL=1-5x10³ copies/mL) and between 10.8% and 14.2% (samples with high VL). The two most used systems gave the following results. System A (275 results) and B (245 results): CV by viral target ranged between 2.4-3.8% and 6.4-9% (samples with VL=1-5x10³copies/mL) and between 2.8-4.2% and 7.3-11.9% (samples with high VL) respectively. Discussion: within 2021 EQA for SARS-CoV-2 molecular test, PPA and NPA were above 99.1%. However, the inter-assay variability among systems was notable and related both to viral load and to viral target detected by the test. This variability, thought limited, needs to be carefully evaluated and continuously monitored within quality assurance programs. [ABSTRACT FROM AUTHOR]

Introduction: new equations for the estimation of the glomerular filtration rate (eGFR) have been recently proposed. Equation changes may result in differences regarding the Chronic Kidney Disease (CKD) classification of the studied populations. Methods: the serum creatinine-based equations elaborated by Modified Diet for Renal Disease Study (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 and 2021, European Kidney Function Consortium (EKFC) were compared for correlation, concordance and effect on CKD staging. Serum creatinine concentration from 38118 consecutive subjects (18 to 75 years, 51% female) were measured by an IDMS traceable method. Results: compared to the 2009 CKD-EPI, the mean difference (limits of agreement) of the MDRD, 2021 CKD-EPI and EKFC equations were -5.8 (-19.3 to 7.8), 3.4 (1.0 to 5.9), -4.9 (-12.6 to 2.7) mL/min x 1.73m² respectively. The concordance, in the same comparisons, was evaluated as excellent (K-Cohen >0.80). The prevalence of CKD [Kidney Disease: Improving Global Outcomes (KDIGO) classes G3a to G5] was 7.6% by MDRD, 5.9% by CKD-EPI 2009, 7.6% by EKFC and 4.8% according to CKD-EPI 2021. The recognized MDRD equation limits regarding age ranges and normal/high eGFR values were confirmed. Discussion: these data confirm that MDRD equation has less accuracy and limited age-related applicability. The other three studied equations demonstrate high level of correlation and very small quantitative differences. However, these differences significantly affect the staging and prevalence of CKD, especially for mild to moderate classes. Awareness of the problem and appropriate communication are required to be addressed before any change to the eGFR equations can be prosed and used. Greater worldwide harmonization of the eGFR would also be desirable. [ABSTRACT FROM AUTHOR]

Background: sepsis is a serious disease with high mortality rate, threatening human health. Clinicians need to diagnose the condition in time to develop an effective treatment plan; therefore, a quick and early screening to rule in or rule out sepsis has become an urgent problem in clinical laboratories. Different markers are used to diagnose sepsis, but they have limitations and require additional examination. The aim of this study is to use leucocyte count and other haematological parameters obtained by Mindray BC-6800-plus, to identify sepsis biomarkers that are early, quickly, conveniently, and at low cost. Methods: a total of 479 venous whole blood samples were collected: 63 control samples (blood donors), and 416 samples hospitalized at the emergency department with symptoms attributable to sepsis with a procalcitonin request. Morphometric parameters are reported using Mindray BC-6800 plus analyzer: white blood cell count-related parameters like cell population data named X, Y, Z, neutrophil-lymphocyte ratio, and index of immature granulocytes. Statistical analysis was performed using the Kruskal-Wallis test to evaluate significative differences among the groups. ROC curves were also examined to extrapolate a cut-off of pathogenicity. Results: we found a significant statistically difference between the control and the sepsis groups for a number of haematological parameters. The ROC curves highlight acceptable sensitivity and specificity values for some parameters, and suggest possible cut-offs. Discussion: some qualitative and quantitative parameters of total count blood can be of help with the screening of sepsis upon admission to the emergency department. [ABSTRACT FROM AUTHOR]

Introduction: cryoproteinemia is associated with a broad spectrum of clinical symptoms and significant variability among patients; in this context, laboratory diagnostics play a crucial role in diagnosis and treatment. However, diagnosing cryoglobulinemia is difficult from a clinical point of view and in the laboratory. SIBioC (Italian Society of Clinical Biochemistry and Molecular Biology) has proposed a survey to the Italian laboratories to assess the adopted methods. Methods: the survey consisted of 40 questions: 8 concerning general items, 9 on the pre-analytical phase, 14 on the analytical phase, 4 on the post-analytical phase, and 5 on the cryofibrinogen. Results: sixty-six laboratories responded to the survey, mainly from Northern Italy. The results show non-homogeneous situation. Preanalytical phase: some laboratories are not equipped with adequate devices for transporting the sample maintaining a temperature-controlled chain. Analytical phase: not all laboratories apply the same procedures to separate the serum, to wash the cryo-precipitate and to measure the cryocrit. Postanalytical phase: almost all laboratories apply the Brouet classification. 11% of laboratories perform cryofibrinogen testing, 20% participate in an external quality assessment, and 62% of participants feel the need for an adequate scientific information and training. Conclusions: the survey shows that the procedures for cryoprotein testing vary widely among laboratories. The need of recommendations emerges strongly; these could start from the existing literature in the field, the already available procedures, trying make a synthesis where the processes are diversified. It is also crucial to participate to External Quality Assessment and to spread the culture of continuous dialogue with clinicians. [ABSTRACT FROM AUTHOR]

Introduction: point of care testing (POCT) is an alternative near to the patient approach to laboratory testing that should generate results comparable to those obtained in laboratory. In our study, we estimated the concordance of the blood cell count carried out on Norma Icon-5 POCT analyzer with that performed in laboratory on an automated blood cell count analyzer (Sysmex XN1000), to evaluate the possible utilization of the POCT in the Emergency Department (ED). Methods: Venous blood samples were collected in tubes containing K3EDTA anticoagulant from 40 patients admitted to the ED. The degree of concordance between POCT results of red blood cells (RBC), white blood cells (WBC), platelets (PLT) count and haemoglobin (Hb) concentration were evaluated. Results: The POCT versus XN1000 bias was -2.44% (95%CI: -3.45 to -1.43), 0.61% (95%CI: -0.70 to 1.92), 1.22% (95%CI: 0.612 to 1.83) and -10.45% (95%CI: -12.33 to -8.67) for RBC, WBC, Hb and PLT respectively. Passing-Bablok regression equation was y=-0.015 (95%CI: -0.309 to 0.240) +0.976x (95%CI: 0.915 to 1.0435); y=-0.186 (95%CI: -0.404 to 0.012) + 1.038x (95%CI: 1.008 to 1.068); y=-1.889 (95%CI: -7.224 to 1.500) + 1.030x (95%CI: 1.000 to 1.069) and y=-12.098 (95%CI: -21.500 to -3.824) + 0.964x (95%CI: 0.924 to 1.000) for RBC, WBC, Hb and PLT respectively. Conclusion: The blood cell counter POCT results were statistically concordant with those of the laboratory system only for WBC count, but showed a clinically acceptable bias also for RBC count and Hb concentration values. However, PLT showed an underestimation statistically significant and also exceeding the minimum clinical allowable bias. Therefore, the POCT blood cell counter can be used for clinical purpose only for RBC, WBC and Hb determination. [ABSTRACT FROM AUTHOR]

Artificial Intelligence (AI) introduced a new era of possibilities into Medicine and promises considerable socio-economic benefits and improvements in individual and public health. Although lagging behind other medical specialties, laboratory medicine is beginning to invest in AI, particularly in machine learning and deep learning applications. Despite many encouraging results, the clinical impact of AI models in clinical medicine is hindered by incorrect study design, reduced sample size, wide heterogeneity of algorithms and performance metrics used, as well as weak validation strategies. This review aims to present a balanced vision of the potential applications of AI in Medicine, opportunities and benefits, without minimizing or neglecting limitations or risks. A range of possible solutions to deal with potential threats are also discussed. In order to be an actor and no longer a spectator, specialists in Laboratory Medicine are encouraged to experiment and practice with these new concepts and methods, being engaged in multidisciplinary teams and multicentric studies. [ABSTRACT FROM AUTHOR]

Allergic diseases are among the top chronic diseases in Europe and developing countries, and the World Health Organisation now considers allergy a 'non-communicable, out-of-control disease' with a possible increase in prevalence of up to 50% in the latest generation. Allergology transversally involves different medical specialities, affecting different organs and apparatuses and opening up to numerous varieties of clinical pictures. In parallel, the Allergy Diagnostic Laboratory is assuming a major role in helping to provide a personalised, targeted and accurate approach for the allergic patient, based on the preliminary detection of an individual sensitisation profile. The aim of this document is to illustrate the whole range of new resources that Laboratory Medicine can provide for initial diagnostic guidance for Allergy, directing selected patients into the appropriate pathway, and referring those who really need an accurate specialist examination to the allergist. In a following document (part 2), specific allergies will be considered: food allergies, allergies to hymenoptera venoms and professional allergies (i.e. latex). [ABSTRACT FROM AUTHOR]

Driving under the influence of psychoactive substances has been shown to increase the risk of involvement in road traffic collisions. The assumption of these substances may impair the visual, cognitive, and/or motor abilities needed for safe driving. Over the years, countries have developed different strategies in order to face this relevant issue. In Italy the interdiction of driving in a state of psycho-physical impairment after taking narcotic and psychotropic substances is governed by the article of Legislative Decree n. 285/1992 but a series of interpretative and practical application issues leave its application to the different operators and especially to the police, the judicial authorities and the health structures; as a consequence, the results are not compliant. Hence the need to make available a shared technicalscientific document on analytical protocols and threshold values that can be used for the analysis and interpretation of narcotic and psychotropic substances in blood, in order to ascertain a possible psycho-physical impairment state due to the use of such substances in drivers. [ABSTRACT FROM AUTHOR]

The principal aim of this document is to provide a detailed documentation of the scientific activity carried out by the Italian Study Group on Cardiovascular biomarkers during these last three difficult years characterized by COVID-19 pandemic, that has put in strain the activity of all clinical laboratories (not only in Italy). Another important aim of this document is to discuss some important pathophysiological and clinical issues related to cardiac-specific biomarkers (i.e., cardiac natriuretic peptides and cardiac troponins), that still need not only further theoretical investigation, but also some multicenter clinical trials in order to evaluate and to improve their utilization in diagnosis, prognosis and managing of patients with cardiovascular disease. [ABSTRACT FROM AUTHOR]