Articoli in pubblicazione

The Biological Variation Data Critical Appraisal Checklist (BIVAC) has been designed to evaluate biological variation (BV) studies and the reliability of the associated BV estimates. To illustrate its utility, two studies delivering within-subject BV (CVI) data for S100-β protein and neuron-specific enolase (NSE), markers typically used for melanoma and neuroendocrine tumors, respectively, were appraised using BIVAC. Data from the European Biological Variation Study (EuBIVAS) and the recently published Johnson et al. study (ref n 11) were scored using the 14 BIVAC quality items (QI), with alternatives A, B, C and/or D to verify whether the elements required to obtain reliable BV data, were present and appropriately documented. Grade A indicates compliance with all the QIs and D indicates non compliance. The sizes of the confidence interval (CI) around the CVI estimates were also compared. Johnson’s study received a BIVAC grade C, EuBIVAS a grade A. EuBIVAS is a large scale study, with 1609 and 1728 results for NSE and S100-β, respectively. In Johnson’s study, only 40 results were available. The EuBIVAS CVI estimates [NSE, 10.9% (10.3-11.5); S100-β , 10.2% (9.6-10.7)] were clearly lower than Johnson’s CVIs [NSE, 22.1% (9.9-34.3); S100-β, 18.9% (8.5-29.4)]. The overlapping CI between the two estimates are caused by Johnson’s CI being about 20 times larger than the corresponding EuBIVAS CI. It is likely that studies that do not comply with all BIVAC QI deliver less reliable, and possibly too high, CVI estimates. Adherence to the BIVAC ensures safe clinical application of BV estimates.

 The prevalence of consultations of general practitioners (GPs) is huge, and for an unknown number of patients a consistent amount of diagnostic laboratory tests is requested. One of the tasks of GPs is to identify patients in need of specific laboratory tests, to improve the patient outcomes taking at the same time into consideration the risk of over-diagnosis and treatment and the available resources as well. To support GPs in their decisional process, we developed a dedicated software application (APP) for mobile devices; the APP contents were developed in collaboration with GPs, with students of a GP training course and with laboratory medicine specialists. We identified the laboratory tests useful for the management of the most frequent diseases observed in GPs' offices,  that are supported by the best available evidence. The first attempt was made considering blood hypertension. Aim of the paper is the description of the process of the APP development,  that  includes data available from national and international guidelines. This promising tool could help GPs to prescribe suitable laboratory tests in different clinical scenario (diagnosis, evaluation of therapy, monitoring) and to promote the implementation of the evidence-based practice of laboratory medicine, reducing the requests of inappropriate tests and accurately identifying patients who need a second level referral (nephrologist, endocrinologist).

The sustainability of the National Health Service is a current subject of debate  due to the pressure that the changes in our societies are having on health systems. Reviewing diagnostic processes is increasingly urgent to contain costs and to maintain the quality of the health services provided.The Evidence Based Laboratory Medicine (EBLM) approach allows to identify and eliminate obsolete methods, replacing them with more adequate ones. The EBLM approach can also provide higher diagnostic accuracy, a rationalisation of diagnostic pathways, a reduction of turnaround-time and a decrease of costs. To reach these objectives, a careful analysis of production processes and assessment of the costs are both necessary. The EBLM approach has been applied to the Protein Unit of Laboratory of Modena. The change in the workflow of the Bence Jones protein determination and the consolidation of the measurement of a number of serum proteins on clinical chemistry analysers allowed a better diagnostic accuracy coupled to important economical savings. The savings made it possible to extend the availability of the free light chains measurements (that before was restricted to patients admitted to the haematology department) to the out-patients of the Province of Modena. The EBLM approach is the most effective way to reach such objectives: really, providing better quality performance does not necessarily correspond to an increase of costs. In addition to developing an adequate level of scientific expertise, the laboratory professional must acquire managerial skills to introduce up-to-date diagnostic methods and to optimize the use of assigned resources, in all areas of laboratory medicine.

The toxicology laboratories were created at the end of 1996 within the city area of Naples (Italy) and, so far, have gained an important experience. Their tasks are to monitor drug abuse, the use of metadone and buprenorphine and the diagnosis and monitoring of alcoholism through the screening of urine and serum samples. From this long-lasting experience, we realized that one of the main critical concern of this activity is the implementation and the maintenance of the custody chain, that is especially needed in the presence of forensic issues. The aim of this paper is to analyze the Italian national and regional laws and administrative indications on this topic. We dedicated a particular interest to the rules established by the Regione Campania, where the laboratory is situated. After considering that a high percentage of samples non-conformities were due to the lack of a proper chain of custody (i.e. 66.7%), we adopted a specific procedure based on the use of a dedicated kit containing both the tubes for a safe sample collection and the related documents. A large amount of time was dedicated to illustrate and diffuse the procedure to the nurses and the other personnel working mainly in the First Aid centers of the Azienda Sanitaria Locale of Naples. The collected data show that the percentage of the unsuitable samples decreased to 38% at the end of the year 2017 when the information and training courses succeeded in involving all the dedicated personnel. We plan to revise periodically the procedures and reinforce the message to further optimize the results

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.

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.

A case of lymphadenopathy, hepatosplenomegaly and elevated serum tryptase level. Mastocytosis is a rare clonal disease characterized by neoplastic proliferation of mast cells in one or more organs, frequently skin and bone marrow. Diagnosis and classification of mastocytosis is based on the identification of neoplastic mast cells in according to the morphological, immunophenotypical and/or molecular criteria established by the WHO. For the diagnosis, serum levels of the tryptase which correlate with quantity and activity of mast cells is particulary useful. This case reports about a 60-year-old man with hepatosplenomegaly, modest monoclonal component, reactive lymph node hyperplasia and moderate macrocytic anemia (haemoglobin:129 gr/L). Bone marrow aspiration shows areas of infiltration of atypical mast cells type II and rarely type I with aberrant immunophenotype: CD45++CD117++CD2+CD25+. The tryptase concentration is significantly increased. According to WHO 2008 criteria, diagnosis of systemic mastocytosis is made. Early diagnosis of mastocytosis is pivotal because immunotherapy is often required to reduce the risk of allergic reactions or major bone complications.

Intraocular hemorrhage in a patient with acquired hemophilia A. Intraocular hemorrhage is frequently encountered by ophthalmologists and by emergency room professionals as well. Although the diagnosis of intraocular hemorrhage is  easy  by fundoscopic examination or ultrasonography, further investigation may be required to determine the underlying etiology. In the literature, several cases of intravascular bleeding caused by the use of warfarin and new oral anticoagulants (NOACs) are described. We report here  a case of intraocular hemorrhage in a patient with acquired hemophilia A (AHA).

Evaluation of response to treatment in a patient with light chain amyloidosis and low free light chain burden. In patients with light chain (AL) amyloidosis, reduction of amyloidogenic circulating free light chain (FLC) concentration translates in improvement of organ dysfunction and is associated with an increase in overall survival. Validated criteria for hematologic response to therapy are based on FLC quantification. However, patients with a difference between involved and uninvolved FLC (dFLC) <50 mg/L are not evaluable for hematologic response. Here we report the case of a 69 year old man with AL (λ) amyloidosis with renal involvement, presenting a low-FLC burden (dFLC 41 mg/L) at diagnosis. After two lines of treatment, a profound reduction of amyloidogenic FLC (dFLC 0 mg/L) was associated with an improvement of organ dysfunction. This case emphasizes the role of FLC assessment in the monitoring also of patients with a low-dFLC burden.