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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]

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 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]

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]

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]

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]

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]

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]

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]

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]