Introduction: This guideline (GL) is aimed at providing a reference for the management of prolactin (PRL)-secreting pituitary adenoma in adults. However, pregnancy is not considered.Methods: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinologi (AME) has identified potentially relevant outcomes, which have then been rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" have been considered in the systematic review of evidence and only those classified as "critical" have been considered in the formulation of recommendations.Results: The present GL provides recommendations regarding the role of pharmacological and neurosurgical treatment in the management of prolactinomas. We recommend cabergoline (Cab) vs. bromocriptine (Br) as the first-choice pharmacological treatment to be employed at the minimal effective dose capable of achieving the regression of the clinical picture. We suggest that medication and surgery are offered as suitable alternative first-line treatments to patients with non-invasive PRL-secreting adenoma, regardless of size. We suggest Br as an alternative drug in patients who are intolerant to Cab and are not candidates for surgery. We recommend pituitary tumor resection in patients 1) without any significant neuro-ophthalmologic improvement within two weeks from the start of Cab, 2) who are resistant or do not tolerate Cab or other dopamine-agonist drugs (DA), 3) who escape from previous efficacy of DA, and 4) who are unwilling to undergo a chronic DA treatment. We recommend that patients with progressive disease notwithstanding previous tumor resection and ongoing DA should be managed by a multidisciplinary team with specific expertise in pituitary diseases using a multimodal approach that includes repeated surgery, radiotherapy, DA, and possibly, the use of temozolomide.Conclusion: The present GL is directed to endocrinologists, neurosurgeons, and gynecologists working in hospitals, in territorial services or private practice, and to general practitioners and patients.

Prolactinomas are the most frequent pituitary adenomas. Prolactinoma may occur in different clinical settings and always require an individually tailored approach. This is the reason why a panel of Italian neuroendocrine experts was charged with the task to provide indications for the diagnostic and therapeutic approaches that can be easily applied in different contexts. The document provides 15 recommendations for diagnosis and 54 recommendations for treatment, issued according to the GRADE system. The level of agreement among panel members was formally evaluated by RAND-UCLA methodology. In the last century, prolactinomas represented the paradigm of pituitary tumors for which the development of highly effective drugs obtained the best results, allowing to avoid neurosurgery in most cases. The impressive improvement of neurosurgical endoscopic techniques allows a far better definition of the tumoral tissue during surgery and the remission of endocrine symptoms in many patients with pituitary tumors. Consequently, this refinement of neurosurgery is changing the therapeutic strategy in prolactinomas, allowing the definitive cure of some patients with permanent discontinuation of medical therapy.

Vitamin D deficiency is very common and prescriptions of both assay and supplementation are increasing more and more. Health expenditure is exponentially increasing, thus it is timely and appropriate to establish rules. The Italian Association of Clinical Endocrinologists appointed a task force to review literature about vitamin D deficiency in adults. Four topics were identified as worthy for the practicing clinicians. For each topic recommendations based on scientific evidence and clinical practice were issued according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) System. (1) What cut-off defines vitamin D deficiency: even though 20 ng/mL (50 nmol/L) can be considered appropriate in the general population, we recommend to maintain levels above 30 ng/mL (75 nmol/L) in categories at risk. (2) Whom, when, and how to perform screening for vitamin D deficiency: categories at risk (patients with bone, liver, kidney diseases, obesity, malabsorption, during pregnancy and lactation, some elderly) but not healthy people should be screened by the 25-hydroxy-vitamin D assay. (3) Whom and how to treat vitamin D deficiency: beyond healthy lifestyle (mostly sun exposure), we recommend oral vitamin D (vitamin D2 or vitamin D3) supplementation in patients treated with bone active drugs and in those with demonstrated deficiency. Dosages, molecules and modalities of administration can be profitably individually tailored. (4) How to monitor the efficacy of treatment with vitamin D: no routine monitoring is suggested during vitamin D treatment due to its large therapeutic index. In particular conditions, 25-hydroxy-vitamin D can be assayed after at least a 6-month treatment. We are confident that this document will help practicing clinicians in their daily clinical practice.

Background: Urine culture is the most frequently requested test for a Microbiology Lab. A reliable screening tool would be of paramount importance both to clinicians and laboratorians, provided that it could get fast and accurate negative results in order to rule-out urinary tract infection (UTI).Materials and methods: We evaluated 1907 consecutive urine samples from outpatients. Culture was performed on chromogenic agar with 1 mu L loop, using 105 CFU/mL as a limit of positive growth. Using Sysmex Uf-1000i analyzer we evaluated bacteria forward scatter (B_FSC) and fluorescent light scatter (B_FLH) in a preliminary discrimination step for UTI caused by Gram+ or Gram- bacteria.Results: We got 512 positive samples. A mono-microbial infection was observed in 490 samples; two bacterial strains were isolated in 22 samples, so 534 bacterial strains were found: 392 Gram, 133 Gram+ and 9 yeasts. Comparing Gram+ and Gram- bacteria we observed a statistically significant difference for B_FSC but not for B_FLH. In this application experimental cut-off value for B_FSC was 25ch. Using this cut-off to perform a presumptive identification of UTI sustained by Gram-+ bacteria, we observed a SE 0.68, SP 0.84.Conclusion: Our data although preliminary suggest that B_FSC could be useful in presumptive exclusion of UTI caused by Gram-positive bacteria. (C) 2014 Elsevier B.V. All rights reserved.

Objective: We performed a multicenter study to calculate the upper reference limits (URL) for urine particle quantification in mid-stream samples by using automated urine analyzers.Design & methods: Two laboratories tested 283 subjects using a Sysmex UF-100, two other laboratories tested 313 subjects using Sysmex UF-1000i, whereas two other laboratories tested 267 subjects using Iris IQ (R) 200.Results: The URLs of UF-100 in females and males were 7.8/mu L and 6.7/mu L for epithelial cells (EC), 11.1/mu L and 9.9/mu L for red blood cells (RBC), 10.2/mu L and 9.7/mu L for white blood cells (WBC), and 0.85/mu L and 0.87/mu L for cylinders (CAST). The URLs of UF-1000i in females and males were 7.6/mu L and 7.1/mu L for EC, 12.2/mu L and 11.1/mu L for RBC, 11.9/mu L and 11.7/mu L for WBC, and 0.88/mu L and 0.86/mu L for CAST. The URLs of Iris IQ (R) 200 in females and males were 7.8/mu L and 6.6/mu L for EC, 12.4/mu L and 10.1/mu L for RBC, 10.9/mu L and 9.9/mu L for WBC, and 1.1/mu L and 1.0/mu L for CAST.Conclusion: The URLs obtained in this study were comparable to the lowest values previously reported in the literature. Moreover, no gender-related difference was observed, and analyzer-specific upper reference limits were very similar. (C) 2013 Elsevier B.V. All rights reserved.

Why this document Neuroendocrine neoplasms (NENs) can arise almost throughout the entire body and share common morphological, ultrastructural, and immunohistochemical characteristics. Neuroendocrine neoplasms are an emerging entity that can occur at any age, with the median age at diagnosis in the late fifth decade and an age-related incidence increase. About two-thirds involve the gastro-entero-pancreatic (GEP) tract and epidemiological studies show their increasing incidence [1]. In the last decades, the overall reported incidence of GEP-NENs increased from 1.0 to 5.25/100.000 persons/year, with a present estimated prevalence of 35/100.000 [1–10]. Physicians’ awareness, endoscopic screening and increased sensitivity of diagnostic tools may at least in part explain this growing trend. Most guidelines are focused on staging, treatment and follow-up of NENs. However, an appropriate clinical suspicion and a correct diagnostic work-up are critical starting points. A multidisciplinary approach, moreover, is crucial to provide a timely and integrated care. Hence, this document is neither a review, nor a guideline; rather, it is a clinical guide for a stepwise and integrated diagnostic work-up of GEP-NENs. Hopefully, this will result in a correct utilization of resources and optimization of the cost/benefit ratio.

Evacuated systems for collection of venous blood are integrated systems of medical and in vitro diagnostic medical devices regulated under European Directives and Italian Legislative Decrees. Both Directives and Decrees endorse the requirement that the whole combination of devices, representing an integrated apparatus, must be safe and not impair the specific performance of each single device. According to mandatory requirements, manufacturers must ensure full compatibility between each component of the system, while the users are responsible for verifying the compatibility of different devices in order to avoid potential quality and safety problems. The acquisition of various devices from different manufacturers may lead to combinations that are not validated by manufacturers themselves and are thus expected to be validated and verified by the users to demonstrate that the system remains safe and will not impair the performance of the individual elements. Therefore, the possibility of purchasing different devices separately should be carefully weighted in terms of risk-benefit, taking into consideration the additional costs of the validation/ verification process that should be carried out by the potential user. Since preanalytical problems are the major source of errors in the total testing process, the selection and acquisition of close evacuated systems for blood collection should be considered a critical issue for assuring quality, safety and efficiency of the preanalytical phase of laboratory diagnostics and, therefore, of the total testing process.

Il prelievo venoso rappresenta una procedura inevitabile per ottenere campioni biologici per l’esecuzione dei test di laboratorio. Malgrado la pratica della flebotomia sia sovente considerata semplice e scevra da complicazioni e complicanze, essa causa la maggior parte degli errori di laboratorio, determinando inaccuratezza dei risultati se eseguita con imperizia, negligenza e scarsa professionalità. Si è quindi ritenuto opportuno provvedere alla redazione di un documento nella forma semplificata di checklist, composta da un semplice ma esaustivo elenco di attività da svolgere o da verificare da parte del prelevatore, al fine di prevenire i principali errori di prelievo. Nell’intento dei redattori e delle Società italiane di Medicina di Laboratorio, questa sintetica checklist rappresenta uno strumento modulabile e potenzialmente adattabile ai differenti contesti locali, diffondibile in maniera facile e graduale, supportata da evidenze scientifiche e dal consenso di esperti, redatta con il contributo di professionisti di diversi contesti sanitari, aderente alle best practice e che richiede risorse minime per essere implementata. È ragionevole supporre che questo strumento sia in grado di sostenere sia i cambiamenti di sistema sia i cambiamenti dei comportamenti individuali, rafforzando gli standard per la sicurezza di operatori e pazienti, contrastando i possibili fattori di fallimento. Auspichiamo, inoltre, che la checklist possa essere adottata dalle strutture sanitarie in cui si renda necessaria la raccolta di campioni di sangue venoso, adattandola alle caratteristiche dell’organizzazione locale.

The collection of venous blood is central in clinical laboratory activity. Although there is widespread perception that this practice is simple and free of complications and side effects, it is undeniable that the vast majority of laboratory errors arises from ignorance, incompetence or negligence during venipuncture. It has hence become advisable to prepare a document in simplified form of checklist, consisting of a concise but comprehensive list of activities to be completed or verified in order to prevent errors during venous blood collection. In the intention of authors, this synthetic checklist is a modular tool, adaptable to different local contexts, it can be easily and gradually implemented, it is supported by scientific evidence and consensus of experts and created with the support of different healthcare professionals and it is adherent to the best practices and requires minimal resources for implementation. It is reasonable to assume that this checklist may be able to withstand system and individual changes, strengthening the standards for safety of both operators and patients, limiting potential failure patterns. We hope that the checklist may be implemented in all healthcare facilities where routine venous blood collection is performed, after adaptation to suit characteristics of local organization.

Background: Setting specifications for analytical quality is always difficult. The risk-management approach might be a way to do so. In this approach, the definition of the required analytical quality is based on the evaluation of patient risk. Risk derives from the probability of error and from the damage that such an error might cause.Methods: Eight Italian laboratories took part in this experiment. Measurements of glucose and total calcium were taken as examples. Analytical quality was evaluated using a specific ring trial with a frozen serum pool and by means of internal quality-control data. The total allowable error was defined according to biological variation specifications. The probability of error was extracted from the imprecision and comparative bias data of each laboratory. The damage caused by a wrong result was evaluated using the absolute probability judgment approach.Results: According to the iso-risk plots (standardized hyperboles on a graph where the x-axis represents damage and the y-axis represents probability) for glucose, all the laboratories were working with an analytical quality that guaranteed low risk for patients. On the contrary, for total calcium none of the laboratories exhibited sufficient quality to guarantee low risk for patients, the presence of bias being the most relevant problem.Conclusions: The results seem to demonstrate the applicability of the risk approach to the analytical phase, indicating a new possible way to define analytical quality targets.

The presence of hemolysis in a biological blood sample is mainly caused by hemolytic anemia or hemolysis in vitro. The latter is caused by inappropriate collection and processing of biological samples, which may affect the reliability of test results. Hemolysis is assessed by free hemoglobin quantification, whose limit is 0.02 g/L in plasma and 0.05 g/L in serum, and visually observed when the concentration of free hemoglobin exceeds 0.30 g/L. Since hemolysis is the most frequent cause of unsuitable biological samples in clinical laboratories, with a prevalence approaching 3% of all received samples, these recommendations have been drafted specifically to assist laboratory professionals in detection and management of hemolysed specimens. In summary, the recommended approach is based on: (i) systematic detection and quantification of hemolysis, by visual inspection and subsequent quantification of the hemolysis index on all samples with visually detectable hemolysis;(ii) immediate notification to the referring department of the presence of hemolysis in the sample, as locally determined; (iii) suppression of all results affected by the presence and/or degree of hemolysis; and (iv) timely request of a second sample, on which the previously deleted tests can be performed.

La presenza di emolisi in un campione biologico è causata principalmente da anemia emolitica o emolisi in vitro. La seconda circostanza è conseguente ad attività inappropriate per la raccolta e il trattamento del campione biologico che possono inficiare l’attendibilità dei risultati di molti esami di laboratorio. L’emolisi è valutabile mediante la determinazione dell’emoglobina libera, il cui limite è 20 mg/L nel plasma e 50 mg/L nel siero. L’emolisi si rende visivamente palese quando la concentrazione di emoglobina libera supera 300 mg/L. Poiché i campioni emolizzati sono la causa più frequente di non conformità dei campioni biologici nei laboratori clinici, con prevalenza prossima al 3% di tutti i campioni ricevuti, queste raccomandazioni di consenso sono state redatte specificatamente per assistere i professionisti di laboratorio nella rilevazione e gestione dei campioni emolitici. In sintesi, l’approccio raccomandato si basa su: (i) rilevazione e quantificazione sistematica dell’emolisi mediante ispezione visiva e successiva determinazione dell’indice di emolisi in tutti i campioni con emolisi visibile; (ii) immediata notifica al reparto della presenza di emolisi del campione secondo modalità definite localmente; (iii) soppressione di tutti i test influenzati dalla presenza e/o grado di emolisi; (iv) richiesta tempestiva di un secondo campione sul quale eseguire gli esami precedentemente soppressi.

Abstract Background: The biochemical determination of cardiac natriuretic peptides, primarily brain natriuretic peptide (BNP) and the amino-terminal fragment of its pro-hormone proBNP (NT-proBNP), are reliable tools for diagnosing cardiac disease, establishing prognosis and evaluating the effectiveness of treatment. These biomarkers have proven to be of particular value in the management of chronic and acute heart failure patients, and in the outpatient and the emergency setting. Methods: A multicenter evaluation was performed to assess the practicability, and the analytical and clinical performance of a new point-of-care testing (POCT) PATHFAST™ NT-proBNP assay. This is an immunochemiluminescent assay using two polyclonal antibodies in a sandwich test format, and performed with a PATHFAST™ automated analyzer. Results: The limit of detection (mean+3 SD of the signal of 20 replicates of the zero calibrator obtained in one run) was 0.535 ng/L. An imprecision study, performed in accordance with the CLSI protocol, showed coefficients of variation of 4.0%–6.4% (within-run imprecision), 0.0%–3.4% (between-run imprecision), 5.5%–7.2% (between-day imprecision), 7.6%–8.9% (total imprecision). The method was linear to 28,755 ng/L. Slopes and intercepts ranged from 0.89 to 0.90 and from 10.96 to 22.85, respectively when lithium-heparin plasma samples (n=100) were used to compare the assay under evaluation with the routine laboratory methods (Dimension RxL®, Stratus® CS). When testing matched samples (n=52), a significant difference was found between the 50th percentile NT-proBNP concentration in K2EDTA whole blood, K2EDTA plasma, lithium-heparin plasma and serum. No significant interference was observed for NT-proBNP in lipemic (tryglicerides up to 28.54 mmol/L), icteric (total and conjugated bilirubin up to 513 and 13 μmol/L, respectively) or hemolyzed (hemoglobin up to 13.50 g/L) samples. The NT-proBNP concentration in a group of 180 healthy donors was significantly influenced by age and gender. In a selected population of patients (n=56) with acute dyspnea admitted to the emergency department, a marked reduction in cardiac natriuretic peptide concentrations was observed in hospitalized patients suffering from heart failure who had a better prognosis compared with those with a poorer prognosis (NT-proBNP mean Δ change, % from –22 to –71 vs. +9 to –11). Conclusions: The satisfactory analytical and clinical performance of the PATHFAST™ NT-proBNP assay, together with its excellent practicability, suggests that it would be a reliable tool in clinical practice, in the emergency setting for point-of-care testing, as well as in the central laboratory. Clin Chem Lab Med 2010;48:1029–34.

Part of this document has been endorsed as a Position Statement on Point of Care testing (in-hospital setting) of the Italian Society of Laboratory Medicine (Societa Italiana di Medicina di Laboratorio, SIMeL) and also refers to official documents and International standards to for generalities (ISO 15189/2003) and specific items (ISO 22870/2006). As such, this article is based on to professional standards, guidelines and peer reviews documents, and it is aimed to improve the pre-analytical, analytical and post-analytical phase of point of care testing (POCT), by providing insights into definitions, key aspects in developing a diagnostic system for POCT, benefits and risks of POCT and leading sources of errors.

Background: Cardiac troponins are considered the cornestore for risk stratification and diagnosis of patients whit acute coronary syndrome (ACS). Following Clinical Laboratory Standards Institute (CLSI) guidelines, we assessed the analytical performances of the Pathfast (R) (Mitsubishi, Japan) cTnI method.Methods: We evaluated different sample types. Control materials and lithium heparin plasma pools were used to determine: limit of blank (LoB), limit of detection (LoD), imprecision and linearity. The effects of potential endogenous interfering substances and the possibility of falsely increased cardiac troponin I (cTnI) concentrations attributable to the presence of heterophilic antibodies (HA), rheumatoid factor (RF) and human anti-mouse antibodies (HAMA) in high concentrations were evaluated. The 99th percentile limit of the cTnI value distribution was determined from 320 Caucasian reference individuals.Results: No significant differences were found when cTnI concentrations of 40 lithium-heparin plasma samples were compared with the matched values of K-2-EDTA plasma, whole blood and serum samples. The LoB and the LoD of the cTnI method were 0.0048 and 0.0066 mu g/L, respectively. cTnI mean values from 0.66 to 6.0 mu g/L showed a total CV% from 6.0 to 6.4. cTnI at a concentration of 0.02 mu g/L was associated with a total CV of 9.6%. The method gave a linear response for cTnI concentrations within the measurement range. In six of 12 samples containing HA, a positive interference was demonstrated. The 99th percentile limit of the cTnI distribution in the reference population was 0.013 mu g/L.Conclusions: The data indicate that the cTnI Pathfast method may be suitable for helping clinicians in the management of patients with ACS. Clin Chem Lab Med 2009; 47: 829-33.

Selfmonitoring of blood glucose (SMBG) performed by point-of-care (POC) instruments in diabetic patients is considered as an integral part of home management of this disease. Accordingly, the current recommendations by the American Diabetes Association for the use of POC in glucose monitoring include the following: (a) to achieve and maintain glycemic control, (b) to prevent and detect hypoglycemia, (c) to prevent severe hyperglycemia, (d) to adjust lifestyle changes, and (e) to determine the need to begin treatment with insulin in gestational diabetes mellitus. However, the results from glucometers are not as accurate as those from laboratory methods, since several factors could affect them: user errors, incorrect calibration and quality control or biological and analytical interferences. These recommendations aim to review the clinical indications for SMGB and to identify essential requirements and goals for proper management, evaluation and use of glucometers at home.

The self-monitoring of blood glucose (SMBG), traditionally performed by “point-of-care” (POC) devices called portable glucose monitors (PGM) is now considered an integral part of managed care of diabetic patients, especially type 1 diabetics and those on insulin therapy. In patients with type 2 diabetes, SMBG can help to achieve a better glycaemic control, although there is not sufficient evidence to attest that strict monitoring in these patients is associated with an improved outcome. The outcome of several clinical studies, especially in diabetics on insulin therapy, has shown that SMBG plays a key role in preventing complications in the short, medium and long term. According to the current recommendations, SMBG is aimed to achieve and maintain glycaemic control, prevent and identify hypoglycaemia, prevent severe hyperglycaemia, adjust lifestyle changes and establish the need to begin treatment with insulin in gestational diabetes mellitus. However, as clearly highlighted by the American Diabetes Association (ADA) and the National Academy of Clinical Biochemistry (NACB), patients and healthcare personnel should be trained on the appropriate use of the device, as well as on the correct interpretation of data. Moreover, definite analytical targets and appropriate acceptance criteria for performance should be fulfilled before a new device is introduced in the hospital environment, or recommended to the patients. Performance limitations such as hematocrit extremes and analytical interferences should be clearly acknowledged by the operators, before taking test results for granted. The current article aims to review the current indications for SMGB and highlight the most important criteria for the appropriate use of PGMs.

Despite some laboratory errors might still occur in the analytical phase, most of them arise on activities that precede (preanalytical phase) or follow (postanalytical phase) sample testing. In particular, a percentage ranging from 60 to 70% of errors occur in the preanalytical phase, particularly in those activities where the human involvement is still necessary (e.g., during venous blood collection). Therefore, consistent with the inevitable subjectivity and with variables related to both the environment and the patient, the collection of suitable flood samples require implementation of appropriate and standardized procedures, whenever possible. The Study Group on "Standardization of extra-analytical variability of laboratory data" has preparated this document to provide recommendations on the proper procedure for collecting venous blood samples.

Critical values (also known as panic or alarm values) highlight a laboratory test result associated with a serious risk for the patient's health, requiring immediate communication to the physician to establish appropriate therapeutic interventions. Although critical values are universally recognized as essential tools for the good laboratory practice, their implementation and management still represent matter of debate. Since the implementation of standardized and universally accepted procedures appears as yet an essential policy to provide rational and efficient solutions to this issue, the present document is aimed to provide consensus recommendations for detection and management of critical values in clinical laboratories. The document is issued by SIBioC and the Italian Society of Laboratory Medicine (SIMeL), together with the Italian Committee for Standardization of Laboratory and Haematological Methods (CISMEL), through the Intersocietary Study Group on Standardization of extra-analytical variability of laboratory results.