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Bone Biopsy (BB) with histomorphometric analysis still represents the gold standard for the diagnosis and classification of different forms of renal osteodystrophy. Bone biopsy is the only technique able to provide comprehensive information on all bone parameters, measuring static and dynamic parameters of turnover, cortical and trabecular microarchitecture, and mineralization defects. In nephrological practice, bone biopsy yields relevant indications to support therapeutic choices in CKD, heavily impacting the management and prognosis of uremic patients. Unfortunately, the use of bone biopsy has decreased; a lack of expertise in performing and interpreting, perceived procedure invasiveness and pain, and reimbursement issues have all contributed to this decline. Nevertheless, both bone biomarkers and instrumental images cannot be considered reliable surrogates for histological findings, being insufficiently accurate to properly evaluate underlying mineral and bone disorders. This is a multidisciplinary position paper from the Nephrology and Osteoporosis Italian Scientific Societies with the purpose of restating the role of bone biopsy in CKD patient management and of providing strong solutions to allow diffusion of this technique in Italy, but potentially also in other countries. The Italian approach through the optimization and standardization of bone biopsy procedure, the construction of the Italian Hub and Spoke network, and a request for adjustment and national homogenization of reimbursement to the Italian Health Ministry has led the way to implement bone biopsy and to improve CKD patient management and prognosis.

Since the beginning of laboratory medicine, the main focus was to provide high quality analytics. Over time the importance of the extra-analytical phases and their contribution to the overall quality became evident. However, as the initial preanalytical processes take place outside of the laboratory and mostly without its supervision, all professions participating in these process steps, from test selection to sample collection and transport, need to engage accordingly. Focusing solely on intra-laboratory processes will not be sufficient to achieve the best possible preanalytical quality. The Working Group for the Preanalytical Phase (WG-PRE) of the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) has provided several recommendations, opinion papers and scientific evidence over the past years, aiming to standardize the preanalytical phase across Europe. One of its strategies to reach this goal are educational efforts. As such, the WG-PRE has organized five conferences in the past decade with the sole focus on preanalytical quality. This year's conference mainly aims to depict the views of different professions on preanalytical processes in order to acquire common ground as basis for further improvements. This article summarizes the content of this 6th preanalytical conference.

Additional file 1: Figure S1. Anti-N antibody titres and dynamics in vaccinated and unvaccinated subjects; Figure S2. Anti-N antibody titres of vaccinated and unvaccinated individuals previously exposed to SARS-CoV-2 infection differ according to age; Figure S3. Correlation among DiaSorin S1/S2, DiaSorin trimeric tests and neutralisation assay; Figure S4. Features of the cohorts analysed in this study. Table S1. Concordance between S1/S2 and trimericS DiaSorin assays.

The TRAPID-AMI (High Sensitivity Cardiac Troponin T assay for rapid Rule-out of Acute Myocardial Infarction) study evaluated a rapid "rule-out" acute myocardial infarction (AMI). We evaluated what symptoms were associated with AMI as part of a substudy of TRAPID-AMI. There were 1282 patients evaluated from 12 centers in Europe, the United States of America, and Australia from 2011 to 2013. Multiple symptom variables were prospectively obtained and evaluated for association with the final diagnosis of AMI. Multivariate logistic regression analysis was done, and odds ratios (OR) were calculated. There were 213/1282 (17%) AMIs. Four independent predictors for the diagnosis of AMI were identified: radiation to right arm or shoulder [OR = 3.0; confidence interval (CI): 1.8-5.0], chest pressure (OR = 2.5; CI: 1.3-4.6), worsened by physical activity (OR = 1.7; CI: 1.2-2.5), and radiation to left arm or shoulder (OR = 1.7; CI: 1.1-2.4). In the entire group, 131 (10%) had radiation to right arm or shoulder, 897 (70%) had chest pressure, 385 (30%) worsened with physical activity, and 448 (35%) had radiation to left arm or shoulder. Duration of symptoms was not predictive of AMI. There were no symptoms predictive of non-AMI. Relationship between AMI size and symptoms was also studied. For 213 AMI patients, cardiac troponins I values were divided into 4 quartiles. Symptoms including pulling chest pain, supramammillary right location, and right arm/shoulder radiation were significantly more likely to occur in patients with larger AMIs. In a large multicenter trial, only 4 symptoms were associated with the diagnosis of AMI, and no symptoms that were associated with a non-AMI diagnosis.

The recent pandemic outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and associated with the pathology called COVID-19 (coronavirus disease 2019), has now become one of the most strenuous health care challenges since the emergence of the three pandemics caused by influenza viruses during the past century. Throughout the clinical decision-making of COVID-19, laboratory tests are essential for supporting the screening, diagnosis, prognostication and therapeutic monitoring of this severe infectious disease. Serological testing, that reflects the humoral immune response developing after interaction between the host and the virus (or its components), enables to garner a vast array of clinical information which can be especially used in seroprevalence or seroconversion studies. To this end, the Task Force on COVID-19 of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) has endorsed a series of technical, practical and clinical ad interim recommendations, aimed at facilitating and optimizing the introduction, clinical usage and governance of SARS-CoV-2 serological immunoassays in routine practice.

Additional file 1: Figure S1. Study flow-chart and design. Figure S2. LDL-cholesterol levels in patients with events according to event site and lipid-lowering treatments.

Receiver operating characteristic curves of the predictive value of plasma copeptin and free cortisol and intensive care unit (ICU) death and poor 12-month outcome. There was no difference in the areas under the curve (AUCs) of copeptin and cortisol for the prediction of ICU mortality (0.91) or poor 12-month outcome (0.97).

Insuline-Naaïve type 2 diabetic patients: a multidimensional evaluation on the role of glycated albuminIntroduction: glycated Albumin (GA) is an innovative glycemic marker, that could be used in the clinical practice, asan add-on strategy, to the traditional glycemic monitoring systems, such as glycated haemoglobin (Hb1Ac) and fastingplasma glucose (FPG). The study aims at presenting the results of a multidimensional analysis conducted in Italy,exploring the main clinical, economic, ethical, social and organizational implications, related to the introduction of GA.Methods: an Health Technology Assessment (HTA) approach was implemented. The analysis considered the ItalianNational Healthcare Service (NHS) perspective, and assumed a 12-month time horizon, focusing on type 2 diabetespatients insulin-naïve, assuming oral therapy. The 9 HTA dimensions (derived from the Core Model developed by theEuropean Network of HTA – EUnetHTA) were deployed, considering scientific evidence, health economics tools andqualitative approaches, through the administration of specific questionnaires to 15 diabetes experts.Results: literature reported better GA safety and efficacy profiles, thus being a predictor of the relative risk for diabetescomplications development, and increasing the therapeutic success after 3 months of therapy (97.0% versus71.6%).From an economic point of view, GA introduction resulted in an economic advantage of 1.06% and in a better trade-off between costs sustained and efficacy gained. Considering a 7-item Likert Scale (ranging from -3 to +3), negativeperceptions emerged with regard to equity aspects (0.13 versus0.72) due to GA limited accessibility, whereas it wouldimprove both patients (2.17 versus1.33) and care givers (1.50 versus0.83) quality of life. In the short term, GArequired training courses and equipment update, whereas, in the long term, it could be considered the preferablesolution from an organizational perspective (0.30 versus0.01).Conclusions: the results of this study demonstrated GA strategic relevance, its economic sustainability and feasibility,as well as the potential clinical pathway improvement.

Vitamin K acts as a coenzyme of carboxylase, catalyzing the carboxylation of several vitamin K dependent proteins. Beyond its well-known effects on blood coagulation, it also exerts relevant effects on bone and the vascular system. In this review, we point out the relevance of an adequate vitamin K intake to obtain sufficient levels of carboxylated (active form) vitamin K dependent proteins (such as Osteocalcin and matrix Gla protein) to prevent bone health. Another bone-related action of Vitamin K is being a ligand of the nuclear steroid and xenobiotic receptor (SXR). We also discuss the recommended intake, deficiency, and assessment of vitamin K. Furthermore, we review the few available studies that have as pre-specified outcome bone fractures, indicating that we need more clinical studies to confirm that vitamin K is a potential therapeutic agent for bone fractures. View Full-Text

Objectives: To assess the diagnostic accuracy of erythrocyte sedimentation rate (ESR) and C- reactive protein (CRP) in acute inflammation. Methods: PubMed and Scopus were searched and eligible articles were screened for methodologic quality using the Quality Assessment of the Diagnostic Accuracy Studies– Revised. Meta-analysis with calculation of pooled sensitivity (Se), specificity (Sp), and summary area under the curve (SAUC) was performed. Results: Twenty-nine studies were eligible. Se and Sp were 0.78 and 0.68 (SAUC = 0.80) for ESR in orthopedic infections and 0.79 and 0.70 (SAUC = 0.81) for CRP. For the diagnosis of other various inflammatory conditions, CRP had a superior diagnostic accuracy, with a Se of 0.86, Sp of 0.67, and SAUC of 0.86 compared with a Se of 0.77, Sp of 0.59, and SAUC of 0.75 for ESR. Heterogeneity among studies was elevated. Combined use of ESR and CRP yielded higher diagnostic accuracy. Conclusions: Despite observed heterogeneity among studies, ESR and CRP have a similar diagnostic accuracy in assessment of inflammation, especially in orthopedic conditions.

Procalcitonin (PCT)-guided antibiotic stewardship (ABS) has been shown to reduce antibiotics (ABxs), with lower side-effects and an improvement in clinical outcomes. The aim of this experts workshop was to derive a PCT algorithm ABS for easier implementation into clinical routine across different clinical settings. Clinical evidence and practical experience with PCT-guided ABS was analyzed and discussed, with a focus on optimal PCT use in the clinical context and increased adherence to PCT protocols. Using a Delphi process, the experts group reached consensus on different PCT algorithms based on clinical severity of the patient and probability of bacterial infection. The group agreed that there is strong evidence that PCT-guided ABS supports individual decisions on initiation and duration of ABx treatment in patients with acute respiratory infections and sepsis from any source, thereby reducing overall ABx exposure and associated side effects, and improving clinical outcomes. To simplify practical application, the expert group refined the established PCT algorithms by incorporating severity of illness and probability of bacterial infection and reducing the fixed cut-offs to only one for mild to moderate and one for severe disease (0.25 μg/L and 0.5 μg/L, respectively). Further, guidance on interpretation of PCT results to initiate, withhold or discontinue ABx treatment was included. A combination of clinical patient assessment with PCT levels in well-defined ABS algorithms, in context with continuous education and regular feedback to all ABS stakeholders, has the potential to improve the diagnostic and therapeutic management of patients suspected of bacterial infection, thereby improving ABS effectiveness.

Laboratory diagnostics in the emergency setting encompasses the identification of appropriate testing according to specific acute conditions. Since the pathway of ordering tests in the Italian Emergency Departments (EDs) is rather heterogeneous, SIBioC-Medicina di Laboratorio and the Academy of Emergency Medicine and Care designed a survey aimed to generate consensus pertaining to appropriate laboratory tests in most frequent acute conditions. A questionnaire including a panel of laboratory tests was administered to 8 representative members of each of the two societies, who were asked to provide a score between 1 and 3 for the various tests, where a score of 1 entailed "highly recommended", 2 "recommended in specific conditions" and 3 identified "highly discouraged" tests. The results of the questionnaire are shown as mean (±SD) of individual responses, thus allowing to define a scale of priority comprised between "highly recommended" and "highly discouraged". Overall, 24 tests were classified as "highly recommended", whereas 6 were "highly discouraged". The remaining 16 tests were classified as "somehow recommended" or "somehow discouraged". In the expectations of the two societies, this document may represent a first step towards harmonizing the laboratory test ordering in Italian EDs.

SUMMARY After a long-standing tradition of analytical quality and analytical quality control programs, most medical laboratories that are aware of the need for total quality management, are experiencing new systems designed to assure quality throughout the entire total testing process, from the pre-analytical to the post-analytical steps. The availability of a new International Standard, ISO 15189:2003, specifically developed and designed to satisfy the requirements for quality management and competence in medical laboratories, should promote the harmonization of accreditation programs at an international level, and implementation of an effective quality system at a local level. The importance of the pre- and post-analytical phases are well recognized in the new International Standard and, therefore, efforts to comply with this standard might assure an approach that safeguards and continuously improves total quality in medical laboratories.

Additional file 2: Intermediate data results. Intermediate results generated step-by-step, following the manuscript details.

Additional file 13: Table S4. The significant MS-MS fragmentation patterns of the serum features analyzed using MALDI-TOF/MS set at CID conditions.

Additional file 9: Table S3. A comparison of MALDI-TOF/MS serum and urinary features. Mean and standard error are reported in arbitrary units. Blank spaces are missing features.

Additional file 5: Results. Monte Carlo simulations results confirmed that substituting the limit of detection (LOD) with LOD/2 does not affect the reliability of ICC estimation; The measurement error structure of peptidomi MALDI-TOF/MS-based analysis of the urinary and serum features

Supplementary Material 1, MSJ779951_supplementary_material_1 for Peripheral imbalanced TFH/TFR ratio correlates with intrathecal IgG synthesis in multiple sclerosis at clinical onset by Marco Puthenparampil, Antonio Zito, Giorgia Pantano, Lisa Federle, Erica Stropparo, Silvia Miante, Giustina De Silvestro, Mario Plebani and Paolo Gallo in Multiple Sclerosis Journal

Additional file 8: Table S2. Free prostate specific antigen (fPSA), total PSA (tPSA), free to total PSA (f/tPSA) and prostate cancer antigen3 (PCA3) median and IQR values for the four classifications utilized in the PCa study.

Supplementary Material 2, MSJ779951_supplementary_material_2 for Peripheral imbalanced TFH/TFR ratio correlates with intrathecal IgG synthesis in multiple sclerosis at clinical onset by Marco Puthenparampil, Antonio Zito, Giorgia Pantano, Lisa Federle, Erica Stropparo, Silvia Miante, Giustina De Silvestro, Mario Plebani and Paolo Gallo in Multiple Sclerosis Journal

Additional file 1: Materials and methods. Urine and serum samples preparation before MALDI-TOF/MS analyses; within and between subject variability of serum MALDI-TOF/MS peptidomic features and variability of MALDI-TOF/MS serum peptidomic features; Within- and between-subjects variability of urinary MALDI-TOF/MS peptidomic analysis; Spectra processing; sLOD estimation of MALDI-TOF/MS peptidomic features; Simulation analyses to examine the reliability of ICC for datasets with measurement error and LOD issues; LOD adjustment, data normalization and log2 transformation of MALDI-TOF/MS features; RCAL and SIMEX for logistic regression analyses.

Additional file 3: Table S1. Monte Carlo simulation results. The ICC estimates were obtained by increasing the measurement error (σε) from 0.01 to 0.64 and considering three different limit of detection (LOD) conditions (12.5%, 25% and 50% of values set below LOD) using four different adjustment methods (Richardson and Ciampi’s method, Schisterman’s method, substitution of W < LOD by zeros and substitution of W < LOD by LOD/2). The mean ICCs and Monte Carlo standard errors are shown.

Supplementary Material 3, MSJ779951_supplementary_material_3 for Peripheral imbalanced TFH/TFR ratio correlates with intrathecal IgG synthesis in multiple sclerosis at clinical onset by Marco Puthenparampil, Antonio Zito, Giorgia Pantano, Lisa Federle, Erica Stropparo, Silvia Miante, Giustina De Silvestro, Mario Plebani and Paolo Gallo in Multiple Sclerosis Journal

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease characterized by the loss of lower motor neurons. SBMA is caused by expansions of a polyglutamine tract in the gene coding for androgen receptor (AR). Expression of polyglutamine-expanded AR causes damage to motor neurons and skeletal muscle cells. Here we investigated the effect of β-agonist stimulation in SBMA myotube cells derived from mice and patients, and in knock-in mice. We show that treatment of myotubes expressing polyglutamine-expanded AR with the β-agonist clenbuterol increases their size. Clenbuterol activated the phosphatidylinositol-3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway and decreased the accumulation of polyglutamine-expanded AR. Treatment of SBMA knock-in mice with clenbuterol, which was started at disease onset, ameliorated motor function and extended survival. Clenbuterol improved muscle pathology, attenuated the glycolytic-to-oxidative metabolic alterations occurring in SBMA muscles and induced hypertrophy of both glycolytic and oxidative fibers. These results indicate that β-agonist stimulation is a novel therapeutic strategy for SBMA.

BACKGROUND We sought to develop estimates of biological variation (BV) for 9 enzymes in blood serum as part of the European Biological Variation Study. METHODS Ninety-one healthy study participants (38 male and 53 female, 21–69 years old) were phlebotomized in each of 10 consecutive weeks at 6 European laboratories. The same preanalytical sample-handling protocol was followed at each center before transport to San Raffaele Hospital, Milan, Italy, for analysis. Sera were stored at −80 °C before analysis in duplicate within a single run on an ADVIA 2400 Clinical Chemistry System (Siemens Healthcare) following a protocol designed to minimize analytical imprecision. Assay traceability was established using frozen sera with target values assigned by reference methods. The results were subjected to outlier analysis before CV-ANOVA to deliver valid BV estimates. Results for 9 enzymes were subsequently partitioned for graphical display allowing visual assessment of the effects of country of origin, sex, and age on BV estimates. RESULTS We found no effect of country upon the observed variation, but overall sex-related differences were evident for alanine amino transferase (ALT), γ-glutamyl transferase (GGT), and creatine kinase (CK). The following estimates for within-subject BV (CVI) and between-subject BV (CVG), respectively, were obtained: ALT: 9.3%, 28.2%; aspartate aminotransferase: 9.5%, 20.3%; GGT: 8.9%, 41.7%; alkaline phosphatase : 5.3%, 24.9%; lactate dehydrogenase: 5.2%, 12.6%; CK: 14.5%, 31.5%; amylase: 6.8%, 30.4%; pancreatic α-amylase: 6.3%, 24.9%; and lipase (LIP): 7.7%, 23.8%. CONCLUSIONS All CVI and some CVG estimates were lower than those reported in the online BV 2014 updated database. Analytical performance specifications derived from BV can be applied internationally.

Background Sensitization to profilins and other cross-reacting molecules might hinder proper specific immunotherapy (SIT) prescription in polysensitized patients with pollen-related allergic rhinitis (AR). In these patients, component-resolved diagnosis (CRD) might modify SIT prescription by improving the identification of the disease-eliciting pollen sources. Objectives We sought to measure the effect of CRD on SIT prescription in children with pollen-related AR. Methods Children (n = 651) with moderate-to-severe pollen-related AR were recruited between May 2009 and June 2011 in 16 Italian outpatient clinics. Skin prick test (SPT) reactivity to grass, cypress, olive, mugwort, pellitory, and/or Betulaceae pollen was considered clinically relevant if symptoms occurred during the corresponding peak pollen season. IgE sensitization to Phl p 1, Phl p 5, Bet v 1, Cup a 1, Art v 1, Ole e 1, Par j 2, and Phl p 12 (profilin) was measured by using ImmunoCAP. SIT prescription was modeled on SPT responses first and then remodeled considering also CRD according to GA2LEN-European Academy of Allergology and Clinical Immunology guidelines and the opinions of 14 pediatric allergists. Results No IgE to the respective major allergens was detected in significant proportions of patients with supposed clinically relevant sensitization to mugwort (45/65 [69%]), Betulaceae (146/252 [60%]), pellitory (78/257 [30%]), olive (111/390 [28%]), cypress (28/184 [15%]), and grass (56/568 [10%]). IgE to profilins, polcalcins, or both could justify 173 (37%) of 464 of these SPT reactions. After CRD, the SPT-based decision on SIT prescription or composition was changed in 277 (42%) of 651 or 315 (48%) of 651 children according to the European or American approach, respectively, and in 305 (47%) of 651 children according to the opinion of the 14 local pediatric allergists. Conclusions In children with pollen-related AR, applying CRD leads to changes in a large proportion of SIT prescriptions as opposed to relying on clinical history and SPT alone. The hypothesis that CRD-guided prescription improves SIT efficacy deserves to be tested. © 2014 American Academy of Allergy, Asthma and Immunology.

Recent single-center and retrospective studies suggest that acute myocardial infarction (AMI) could be immediately excluded without serial sampling in patients with initial high-sensitivity cardiac troponin T (hs-cTnT) levels below the limit of detection (LoD) of the assay and no electrocardiogram (ECG) ischemia.We aimed to determine the external validity of those findings in a multicenter study at 12 sites in nine countries.TRAPID-AMI was a prospective diagnostic cohort study including patients with suspected cardiac chest pain within 6 hours of peak symptoms. Blood drawn on arrival was centrally tested for hs-cTnT (Roche; 99th percentile = 14 ng/L, LoD = 5 ng/L). All patients underwent serial troponin sampling over 4-14 hours. The primary outcome, prevalent AMI, was adjudicated based on sensitive troponin I (Siemens Ultra) levels. Major adverse cardiac events (MACE) including AMI, death, or rehospitalization for acute coronary syndrome with coronary revascularization were determined after 30 days.We included 1,282 patients, of whom 213 (16.6%) had AMI and 231 (18.0%) developed MACE. Of 560 (43.7%) patients with initial hs-cTnT levels below the LoD, four (0.7%) had AMI. In total, 471 (36.7%) patients had both initial hs-cTnT levels below the LoD and no ECG ischemia. These patients had a 0.4% (n = 2) probability of AMI, giving 99.1% (95% confidence interval [CI] = 96.7% to 99.9%) sensitivity and 99.6% (95% CI = 98.5% to 100.0%) negative predictive value. The incidence of MACE in this group was 1.3% (95% CI = 0.5% to 2.8%).In the absence of ECG ischemia, the detection of very low concentrations of hs-cTnT at admission seems to allow rapid, safe exclusion of AMI in one-third of patients without serial sampling. This could be used alongside careful clinical assessment to help reduce unnecessary hospital admissions.

Recommendations for the use of cardiac troponin (cTn) measurement in acute cardiac care have recently been published.1 Subsequently, a high-sensitivity (hs) cTn T assay was introduced into routine clinical practice.2 This assay, as others, called highly sensitive, permits measurement of cTn concentrations in significant numbers of apparently illness-free individuals. These assays can measure cTn in the single digit range of nanograms per litre (=picograms per millilitre) and some research assays even allow detection of concentrations 10% at the 99th percentile URL limiting that ability.5–7 However, the less precise cTn assays do not cause clinically relevant false-positive diagnosis of acute myocardial infarction (AMI) and a CV

Laboratory medicine, as a specialty that had prioritized quality control, has always been at the forefront of error reduction. In the last decades, a dramatic decrease of analytical errors has been experienced, while a relatively high frequency of errors has been documented in the pre-analytical phase. Most pre-analytical errors, which account for up to 70% of all mistakes made in laboratory diagnostics, arise during patient preparation, and sample collection, transportation, preparation for analysis and storage. However, while it has been reported that the pre-analytical phase is error-prone, only recently has it been demonstrated that most of these errors occur in the 'pre-pre-analytical phase', which comprises the initial procedures of the testing process performed outside the laboratory walls by healthcare personnel outside the direct control of the clinical laboratory. Developments in automation and information technologies have played a major role in decreasing some pre-analytical errors and, in particular, the automation of repetitive, error prone and bio-hazardous pre-analytical processes performed within the laboratory walls has effectively decreased errors in specimen preparation, centrifugation, aliquot preparation, pipetting and sorting. However, more efforts should be made to improve the appropriateness of test request, patient and sample identification procedures and other pre-analytical steps performed outside the laboratory walls.

The erythrocyte sedimentation rate (ESR) remains one of the most widely used laboratory tests. Its clinical usefulness and interpretation are in the monitoring of inflammatory diseases, in particular rheumatoid arthritis, temporal arteritis and polymyalgia rheumatica. At present, the reference method for measuring the ESR proposed by the International Committee for Standardization in Haematology (ICSH) utilizes EDTA-anticoagulated-undiluted blood to perform the test using the method described by Westergren in 1921. Current interest in the methodology focuses on the development of an automated closed system that allows the determination of the sedimentation rate with selected working methods, using a single sample for more than one haematological test, improving the bio-hazardous aspects of the testing procedures. As a consequence, standardization becomes necessary. ESR results should be reliable, despite the increased number of different methods and testing variables. Control materials and External Quality Assurance Schemes are now available, and should be used. In conclusion, innovative techniques may improve the appropriateness and usefulness of ESR in clinical practice, but in addition, they need to guarantee the traceability of results in comparison to the reference method in order to ensure comparability of results among different clinical laboratories.

The last few decades have seen a significant decrease in the rates of analytical errors in clinical laboratories, while a growing body of evidence demonstrates that the pre and post-analytical steps of the total testing process (TTP) are more error-prone than the analytical phase. In particular, most errors are identified in pre-preanalytic steps outside the walls of the laboratory, and beyond its control. However, in a patient-centered approach to the delivery of health care services, there is the need to investigate, in the total testing process, any possible defect that may have a negative impact on the patient, irrespective of which step is involved and whether the error depends on a laboratory professional (e.g. calibration or testing error) or a non-laboratory operator (e.g. inappropriate test request, error in patient identification and/or blood collection). In the pre-analytic phase, the frequency of patient/specimens misidentification and the presence of possible causes of specimen rejection (haemolysis, clotting, insufficient volume, etc.) represent a valuable risk for patient safety. Preventing errors in the pre-analytical steps requires both technological developments (wristband, barcodes, pre-analytical workstations) and closer relationships with the clinical world to achieve an effective team-working cooperation. The most important lesson we have learned, therefore, is that laboratory errors and injuries to patients can be prevented by redesigning systems that render it difficult for all caregivers and in all steps of the total testing process to make mistakes.

Calcitonin (CT) is currently the most sensitive serological marker of C-cell disease [medullary thyroid carcinoma (MTC) and C-cell hyperplasia]. Starting with a report on a case that occurred at our institution, this review focuses on trying to explain the reasons behind the poor specificity and sensitivity of the various CT immunoassays. A 15-year-old patient was referred to our institution in May 2014 for moderately elevated CT levels. Thyroid ultrasonography (US) documented a colloidal goiter. Secondary causes of the hypercalcitoninemia (hyperCT) were ruled out. The mismatch between the clinical picture and the laboratory results prompted us to search for other reasons for the patient’s high CT levels, so we applied the heterophilic blocking tube (HBT) procedure to the patient’s sera before the CT assay. Using this pretreatment step, his serum CT concentration dropped to

Pancreatic organ-specific autoimmunity in subjects at risk for type 1 diabetes (T1D) is associated with increased intestinal permeability and an aberrant gut microbiota, but these factors have not yet been simultaneously investigated in the same subjects. Thus, the aim of this study was to assess both intestinal permeability and gut microbiota composition in an Italian sample of children at risk for T1D.Ten Italian children with beta cell autoimmunity at risk for T1D and 10 healthy children were involved in a case-control study. The lactulose/mannitol test was used to assess intestinal permeability. Analysis of microbiota composition was performed using polymerase chain reaction followed by denaturing gradient gel electrophoresis, based on the 16S rRNA gene.Intestinal permeability was significantly higher in children at risk for T1D than in healthy controls. Moreover, the gut microbiota of the former differed from that of the latter group: Three microorganisms were detected - Dialister invisus, Gemella sanguinis and Bifidobacterium longum - in association with the pre-pathologic state.The results of this study validated the hypothesis that increased intestinal permeability together with differences in microbiota composition are contemporaneously associated with the pre-pathological condition of T1D in a sample of Italian children. Further studies are necessary to confirm the microbial markers identified in this sample of children as well as to clarify the involvement of microbiota modifications in the mechanisms leading to increased permeability and the autoimmune mechanisms that promote diabetes onset. Copyright © 2016 John WileySons, Ltd.