Publications by authors named "Matteo Vidali"

60 Publications

Preliminary reference intervals of Glycated Albumin in healthy Caucasian pregnant women.

Clin Chim Acta 2021 Aug 12;519:227-230. Epub 2021 May 12.

Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy; Department of Laboratory Medicine, University Hospital "P. Giaccone", Palermo, Italy. Electronic address:

Background And Aims: Glycated albumin (GA) could represent a useful biomarker in pregnant women for diagnosing and monitoring gestational diabetes mellitus (GDM). The establishment of reference intervals (RI) is mandatory before assessing its clinical usefulness. The RIs of GA in healthy pregnant women are not well defined. The aim of the current study was to establish the RI in a cohort consisting of Caucasian pregnant women without overt diabetes mellitus or gestational diabetes mellitus.

Methods: The study included 183 healthy pregnant women. GA was measured on plasma by an enzymatic method (quantILab Glycated Albumin, IL Werfen, Germany). The RI was calculated by the non-parametric and robust methods.

Results: The RI of GA in the whole population was 10.16% (90%CI 9.60-10.70) and 15.44% (90%CI 14.90-16.90). GA levels decreased during pregnancy, with lower levels in the third trimester: 10.11 (90%CI 9.48-10.79) and 15.72 (90%CI 15.15-16.27) in the first trimester, 10.49 (90%CI 10.05-10.96) and 15.49 (90%CI 15.05-15.92) in the second trimester, 9.84 (90%CI 9.50-10.22) and 14.57 (90%CI 14.11-15.01) in the third trimester. Finally, a weak negative correlation was found between GA levels and body mass index.

Conclusion: This is the first study establishing the RIs of GA in Caucasian healthy pregnant women.
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http://dx.doi.org/10.1016/j.cca.2021.05.009DOI Listing
August 2021

A new tool for sepsis screening in the Emergency Department.

Clin Chem Lab Med 2021 Apr 13. Epub 2021 Apr 13.

Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Palermo, Italy.

Objectives: In this study, we developed and evaluated the diagnostic accuracy of the Sepsis Index for early sepsis screening in the Emergency Department (ED).

Methods: Sepsis Index is based on the combination of monocyte distribution width (MDW) and mean monocyte volume (MMV). Sepsis Index≥1 was selected to define sepsis. We tested its diagnostic accuracy in an ED population stratified in four groups: controls, Systemic Inflammatory Response Syndrome (SIRS), infection, and sepsis, according to Sepsis-2 criteria.

Results: Patients with sepsis displayed higher median Sepsis Index value than patients without sepsis. At the receiver operating characterictis (ROC) curve analysis for the prediction of sepsis, the area under the curve (AUC) of MDW and Sepsis Index were similar: 0.966 (95%CI 0.947-0.984), and 0.964 (95%CI 0.942-0.985), respectively. Sepsis Index showed increased specificity than MDW (94.7 vs. 90.6%), without any decrease in sensitivity (92.0%). Additionally, LR+ increased from 9.8 (MDW) to 17.4 (Sepsis Index), without any substantial change in LR- (respectively 0.09 vs. 0.08). Finally, PPV increased from 0.286 (MDW) to 0.420 (Sepsis Index).

Conclusions: Sepsis Index improves the diagnostic accuracy of MDW alone for sepsis screening.
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http://dx.doi.org/10.1515/cclm-2021-0208DOI Listing
April 2021

FOXP3 and GATA3 Polymorphisms, Vitamin D3 and Multiple Sclerosis.

Brain Sci 2021 Mar 25;11(4). Epub 2021 Mar 25.

Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, 90127 Palermo, Italy.

Background: Regulatory T cells (Tregs) alterations have been implicated in the pathogenesis of Multiple Sclerosis (MS). Recently, a crucial role of the X-Linked Forkhead Box P3 (FoxP3) for the development and the stability of Tregs has emerged, and FOXP3 gene polymorphisms have been associated with the susceptibility to autoimmune diseases. The expression of Foxp3 in Tregs is regulated by the transcription factor GATA binding-protein 3 (GATA3) and vitamin D. The aim of this retrospective case-control study was to investigate the potential association between FOXP3 and GATA3 genetic variants, Vitamin D, and MS risk.

Methods: We analyzed two polymorphisms in the FOXP3 gene (rs3761547 and rs3761548) and a polymorphism in the GATA3 gene (rs3824662) in 106 MS patients and 113 healthy controls. Serum 25(OH)D3 was also measured in all participants.

Results: No statistically significant genotypic and allelic differences were found in the distribution of FOXP3 rs3761547 and rs3761548, or GATA3 rs3824662 in the MS patients, compared with controls. Patients that were homozygous for rs3761547 had lower 25(OH)D3 levels.

Conclusions: Our findings did not show any association among FOXP3 and GATA3 SNPs, vitamin D, and MS susceptibility.
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http://dx.doi.org/10.3390/brainsci11040415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066599PMC
March 2021

Tau protein as a diagnostic and prognostic biomarker in amyotrophic lateral sclerosis.

Eur J Neurol 2021 Jun 19;28(6):1868-1875. Epub 2021 Mar 19.

Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Palermo, Italy.

Background And Purpose: To test the hypothesis that total tau (tTau), tau phosphorylated at threonine 181 (pTau) and pTau/tTau ratio in the cerebrospinal fluid (CSF) are diagnostic and prognostic biomarkers of amyotrophic lateral sclerosis (ALS), we performed a retrospective observational study in a large cohort of ALS patients and controls.

Methods: We enrolled 196 ALS patients and 91 controls, who included patients with ALS-mimicking diseases and those with non-neurodegenerative diseases. All patients underwent lumbar puncture for CSF analysis at the time of the diagnostic evaluation or to first referral. We measured tTau and pTau levels in the CSF by chemiluminescence enzyme immunoassay.

Results: Patients with ALS showed significantly higher levels of CSF tTau and a lower pTau/tTau ratio than controls (tTau: 245 vs. 146 pg/ml; p < 0.001; pTau/tTau ratio: 0.12 vs. 0.18; p < 0.001, respectively). No differences in pTau levels were detected. Receiver-operating characteristic curve analysis showed a good diagnostic accuracy of tTau and pTau/tTau ratio (tTau: area under the curve [AUC] 0.685, 95% confidence interval [CI] 0.616-0.754, p = 0.039; pTau/tTau ratio: AUC 0.777, 95% CI 0.707-0.848, p < 0.001). Among ALS patients, increased tTau levels were associated with advanced age of onset, increased revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) score (ΔFS) rate of progression, and spinal onset. Multivariate analysis showed that in ALS patients, this biomarker was an independent negative predictor of overall survival.

Conclusions: Our findings suggest that tTau and pTau/tTau ratio can be diagnostic biomarkers of ALS. In addition, CSF tTau level at diagnosis might play a relevant prognostic role in the disease.
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http://dx.doi.org/10.1111/ene.14789DOI Listing
June 2021

Validation of monocyte distribution width decisional cutoff for sepsis detection in the acute setting.

Int J Lab Hematol 2021 Feb 26. Epub 2021 Feb 26.

Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy.

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http://dx.doi.org/10.1111/ijlh.13496DOI Listing
February 2021

Standardization and harmonization in hematology: Instrument alignment, quality control materials, and commutability issue.

Int J Lab Hematol 2021 Jun 10;43(3):364-371. Epub 2020 Nov 10.

Clinical Chemistry Laboratory, Hospital Papa Giovanni XXIII, Bergamo, Italy.

Introduction: In the hub and spoke laboratory network, the number of hematology analyzers (HAs) within each core center has increased, and the control of HAs alignment is becoming necessary requirement to ensure analytical quality. In this scenario, HA alignment can be assessed by analyzing the same control material used for internal quality control on multiple HAs, assuming its commutability. The aim of the study was to verify the applicability of a protocol for the alignment of HAs based on control material rather than on fresh whole-blood samples.

Methods: The alignment of five HAs was evaluated for red (RBC, Hb, MCV, RET), white (WBC, NE, LY, MO, EO, BA, IG), and platelet (PLT) series parameters, following a protocol by SIBioC, using human sample (HS) and quality control material (QC), after the verification of commutability, according to the IFCC protocol. Maximum bias was derived from biological variation data.

Results: A complete alignment between instruments was confirmed for the majority of the parameters investigated both for HS and QC material. Partial misalignments or inconcludent results were instead evident for MCV, MO, EO, BA, and IG. Interestingly, QC material was found to be not commutable for LY, MO, and BA.

Conclusion: The alignment of hematologic analyzers for main cell population parameters may be verified with both QC and HS, displaying consistent results and interpretation. The evaluation for some white series parameters (EO, BA, and IG) is critical, and particular attention must be paid to the values of the material used for the alignment.
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http://dx.doi.org/10.1111/ijlh.13379DOI Listing
June 2021

Monocyte distribution width as a biomarker of sepsis in the intensive care unit: A pilot study.

Ann Clin Biochem 2021 01 16;58(1):70-73. Epub 2020 Nov 16.

Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Palermo, Italy.

Background: Monocyte distribution width has been recently proposed as a sepsis biomarker in the emergency department. The aim of this study was to assess the role of monocyte distribution width as a diagnostic biomarker of sepsis in the intensive care unit.

Methods: In this prospective observational study, we included all consecutive patients admitted to the intensive care unit of the University Hospital "P. Giaccone" of Palermo. Patients were classified into three groups according to Sepsis-3 criteria: (1) patients without sepsis; (2) patients developing sepsis during their hospital stay; (3) patients admitted with sepsis. Monocyte distribution width was measured at admission (groups 1, 2, 3) and daily until the developing of sepsis (group 2) or the end of hospitalization (group 1).

Results: Monocyte distribution width was significantly higher in group 3 than group 1 and group 2 (30.9 [25.6-36.0] vs. 20.3 [18.3-23.6] and 21.4 [19.4-25.2]). Among patients belonging to group 2, monocyte distribution width values, measured at the day when sepsis was clinically diagnosed, were significantly higher than those found at admission: 29.4 (26.7-36.0) vs. 21.4 (19.4-25.2),  = 0.001.

Conclusion: Monocyte distribution width could represent a reliable biomarker of sepsis in the intensive care unit.
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http://dx.doi.org/10.1177/0004563220970447DOI Listing
January 2021

Reduced activity of B lymphocytes, recognised by Sysmex XN-2000™ haematology analyser, predicts mortality in patients with coronavirus disease 2019.

Int J Lab Hematol 2021 02 7;43(1):e5-e8. Epub 2020 Sep 7.

Division of Internal Medicine, Department of Translational Medicine, University of Eastern Piedmont Amedeo Avogadro, Novara, Italy.

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http://dx.doi.org/10.1111/ijlh.13331DOI Listing
February 2021

Reference interval of monocyte distribution width (MDW) in healthy blood donors.

Clin Chim Acta 2020 Nov 22;510:272-277. Epub 2020 Jul 22.

Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy; Department of Laboratory Medicine, University Hospital "P. Giaccone", Palermo, Italy. Electronic address:

Background: The aim of the study was to accurately establish the reference interval (RI) of monocyte distribution width (MDW) in healthy blood donors by the direct method using different statistical approaches.

Methods: MDW was measured in 486 subjects. RI of MDW was calculated by the non-parametric method, the robust method and, the Harrell-Davis bootstrap method and using different tests to identify potential outliers (Dixon-Reed and Tukey).

Results: Lower and upper reference limits of the RI calculated by the non-parametric method were, 16.22 (90%CI 15.78-16.47) - 23.15 (90%CI 22.80-24.10) (without outlier removal), and 16.44 (90%CI 16.21-16.67) - 22.99 (90%CI 22.33-23.22) (after outlier removal). The RIs based on the robust method were, respectively, 16.29-22.98 (without) and 16.50-22.67 (with outlier removal). Finally, the RIs calculated by the Harrell-Davis bootstrap method, without or after outlier removal, were 16.19-23.24 and 16.43-22.93. Thus, the RIs obtained by the three calculation methods were very similar. Additionally, no RI partition was done since no significant gender or age association was found.

Conclusions: Our results support the use of a unique RI of MDW, independently of sex and age.
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http://dx.doi.org/10.1016/j.cca.2020.07.036DOI Listing
November 2020

Monocyte distribution width (MDW) as a screening tool for sepsis in the Emergency Department.

Clin Chem Lab Med 2020 10;58(11):1951-1957

Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy.

Objectives The diagnosis of sepsis in the Emergency Department (ED) is challenging and a reliable biomarker is needed. The current study aimed to evaluate the diagnostic accuracy of monocyte distribution width (MDW) for the early identification of sepsis in the ED. Methods We performed a large observational study including consecutive adult patients (≥18 years of age) presenting to the ED between September and November 2019, with an order for complete blood count (CBC) evaluation. A total of 2,215 patients were enrolled and classified based on Sepsis-2 criteria as the control group (1,855), infection group (172), Systemic Inflammatory Response Syndrome (SIRS) group (100), and sepsis group (88). Results MDW levels were higher in patients with sepsis than in all other groups (p<0.001). ROC curve analysis showed an optimal diagnostic accuracy of MDW for sepsis prediction at a cut-off point of 23.5, with an AUC of 0.964, sensitivity and specificity of 0.920 and 0.929, respectively. Conclusions Our findings encourage further investigation to validate the use of MDW as a screening tool for the early identification of patients at risk of sepsis in the ED.
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http://dx.doi.org/10.1515/cclm-2020-0417DOI Listing
October 2020

Multicenter evaluation of analytical performances of platelet counts and platelet parameters: Carryover, precision, and stability.

Int J Lab Hematol 2020 Oct 18;42(5):552-564. Epub 2020 Apr 18.

Clinical Chemistry Laboratory, Papa Giovanni XXIII Hospital, Bergamo, Italy.

Introduction: The correctness of the results of automated platelet analysis is still highly debated. The aim of this multicenter study, conducted according to international guidelines, was to verify the analytical performance of nine different types of hematology analyzers (HAs) in the automated platelet analysis.

Methods: Four hundred eighty-six peripheral blood samples (PB), collected in K EDTA tubes, were analyzed by ABX Pentra, ADVIA2120i, BC-6800, BC-6800 Plus, Cell-DYN Sapphire, DxH800, XE-2100, XE-5000, XN-20 with PLT-F App. Within-run imprecision and between-run imprecision were carried out using PB and material control, respectively. The carryover, low limit of quantification (LoQ), and the PB stability were evaluated.

Results: The carryover was absent for all HAs. The LoQ of PLT ranged between 2.0 (Cell-Dyn Sapphire) and 25.0 × 10 /L (ADVIA 2120i), while immature platelet fraction (IPF) ranged between 1.0 (XN-20) and 12.0 × 10 /L (XE-5000). The imprecision (%CV) increases as the platelet count decreases. No HAs showed desirable CV for PLT counts less than 50.0 × 10 /L, with the exception of Cell-DYN Sapphire (CV 3.0% with PLT-O mean value of 26.7 × 10 /L), XN-20 (CV 2.4% with PLT-F mean value of 21.5 × 10 /L), and BC-6800 Plus (CV 1.9% with PLT-O mean value of 26.5 × 10 /L). The sample stability ranged between under two hours for MPV by ADVIA2120i and 8 hours for other PLT parameters and HAs.

Conclusion: The findings of this study may provide useful information regarding carryover, precision, and stability of platelet counts and parameters, especially in thrombocytopenic samples. Moreover, the stability of sample for platelet analysis is conditioned by the HA and by temperature and storage time.
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http://dx.doi.org/10.1111/ijlh.13204DOI Listing
October 2020

Diagnostic accuracy of cerebrospinal fluid biomarkers measured by chemiluminescent enzyme immunoassay for Alzheimer disease diagnosis.

Scand J Clin Lab Invest 2020 Jul 7;80(4):313-317. Epub 2020 Apr 7.

Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Palermo, Italy.

In the last decades, an important role of cerebrospinal fluid (CSF) biomarkers for Alzheimer disease (AD) diagnosis has emerged. The evaluation of the triad consisting of 42 aminoacid-long amyloid-beta peptide (Aβ42), total Tau (tTau) and Tau phosphorylated at threonine 181 (pTau) have been recently integrated into the research diagnostic criteria of AD. For a long time, the enzyme-linked immunosorbent assay (ELISA) has represented the most commonly used method for the measurement of CSF biomarkers levels. This study aimed to assess the diagnostic accuracy of CSF biomarkers, namely Aβ42, tTau and pTau and their ratio, measured by fully automated CLEIA assay (Lumipulse). We included 96 patients clinically diagnosed as AD (48) and non-AD (48). All CSF biomarkers levels were measured on Lumipulse G1200 fully automated platform (Fujirebio Inc. Europe, Gent, Belgium). Aβ42 levels, 42/40 ratio, 42/tTau ratio, 42/PTau ratio were significantly reduced, and tTau and PTau levels were significantly increased in AD patients in comparison with non-AD patients. The receiving operator curve (ROC) analysis showed good diagnostic accuracy of all CSF biomarkers and their ratios for discriminating AD patients from non-AD patients, with 42/40 ratio having the best AUC (0.724, 95%CI 0.619-0.828;  < 0.001). Our findings support the use of CSF biomarkers measured by CLEIA method on a fully automated platform for AD diagnosis.
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http://dx.doi.org/10.1080/00365513.2020.1740939DOI Listing
July 2020

Biochemical, immunochemical and serology analytes validation of the lithium heparin BD Barricor blood collection tube on a highly automated Roche COBAS8000 instrument.

Acta Biomed 2020 03 19;91(1):47-55. Epub 2020 Mar 19.

Laboratory Medicine Service, San Raffaele Hospital, Milano, Italy.

Background: Recently developed blood tubes with a barrier to provide plasma are becoming widespread. We compared 43 biochemical, 35 immunochemical and 7 serology analytes in a BD-Vacutainer® Barricor tube for local clinical validation of this lithium-heparin tube with a barrier.

Methods: Samples from 70 volunteers were collected in different BD-tubes: a clot-activator tube with gel (SST), a lithium-heparin tube with gel (PST), and a lithium-heparin tube with barrier (BAR). Biases from Bland-Altman plots and 95% confidence intervals were compared with the desirable specification from the Ricos database in order to verify whether measurements from different tubes were significantly different.

Results: For most of the analytes tested, the measurements using SST, PST or BAR tubes were equivalent. Only BIC, GLU, K, LAD, LPA, P, TP, CTX, Ferritin, HGH, vitD3 and ANTIS showed statistically significant, between-tubes, differences which might have clinical implication.

Conclusions: The study demonstrates that SST, PST and BAR can be used interchangeably for most of the analytes tested, including serology analytes. This allows the use of the same tube for assaying multiple analytes, increasing the laboratory efficiency while decreasing patients discomfort by minimizing blood withdrawal.
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http://dx.doi.org/10.23750/abm.v91i1.9195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7569594PMC
March 2020

Lipoprotein-associated phospholipase A2 predicts lower limb ischemia in hemodialysis subjects.

Ther Apher Dial 2020 Oct 21;24(5):548-553. Epub 2020 Jan 21.

Department of Health Sciences, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.

Hemodialyzed patients (HD) have high prevalence of peripheral arterial disease. In the general population, lipoprotein-associated phospholipase A2 (Lp-PLA ) is associated with peripheral arterial disease but no data are available for renal subjects. The aim of this study was to evaluate the relationship between Lp-PLA and lower limb ischemia among dialyzed patients. One hundred and two dialyzed subjects, with median (IQR) age of 71 (59-78) years, enrolled in June 2013 and followed until June 2018, were investigated for Lp-PLA activity and the occurrence of peripheral arterial disease and lower limb ischemia. The median (IQR) levels of Lp-PLA were 184 nmol/min/mL (156.5-214.5). The 43 HD patients with abnormal Lp-PLA activity (>194 nmol/min/mL) had higher levels of total and LDL-cholesterol, ApoB/A1 ratio, and higher occurrence of lower limb ischemia during the follow up (44% vs 17%, P = .003). In multivariate analysis, Lp-PLA activity (P = .018) and diabetes (P < .001) were independently associated with time to lower limb ischemia, and when the presence of previous PAD was added to the multivariate model, only presence of previous PAD (P < .001) and Lp-PLA (P = .003) remained associated. Lp-PLA is an independent predictor of lower limb ischemia in dialyzed patients.
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http://dx.doi.org/10.1111/1744-9987.13465DOI Listing
October 2020

Reference interval by the indirect approach of serum thyrotropin (TSH) in a Mediterranean adult population and the association with age and gender.

Clin Chem Lab Med 2019 Sep;57(10):1587-1594

Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy.

Background The serum concentration of thyrotropin (TSH) represents a first-line test in diagnostic algorithms. The estimation of TSH reference intervals (RIs) is still a matter of debate due to the high prevalence of subclinical disease making difficult the definition of truly healthy subjects. The aim of this study was to estimate TSH RIs in healthy subjects and to evaluate the effect of age and gender on TSH concentration. Methods Forty-four thousand one hundred and fifty-six TSH data were collected between July 2012 and April 2018 at the Department of Laboratory Medicine, University-Hospital, Palermo. Common and sex-specific RIs were estimated by Arzideh's indirect method after exclusion of individuals younger than 15 years, subjects with repeated TSH tests and with abnormal free thyroxine (fT4), free triiodothyronine (fT3) or anti-thyroid-peroxidase antibodies. The combined effect of age and gender on TSH values was evaluated. Results RIs estimated in the selected individuals (n = 22602) were, respectively, 0.18-3.54 mIU/L (general), 0.19-3.23 mIU/L (men) and 0.18-3.94 mIU/L (women). Women showed significantly higher median TSH than men (1.46 vs. 1.39 mIU/L; p < 0.0001). Both in men and in women, median TSH decreased along with age; however, although up to 60 years in both men and women showed similar values, afterwards women showed constantly higher TSH than men. Accordingly, statistical analysis showed a significant interaction between gender and age (p = 0.001), suggesting that the effect of age on TSH is different between genders. Conclusions Our findings suggest that the indirect method, with appropriate cleaning of data, could be useful to define TSH RIs.
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http://dx.doi.org/10.1515/cclm-2018-0957DOI Listing
September 2019

A collaborative study by the Working Group on Hemostasis and Thrombosis of the Italian Society of Clinical Biochemistry and Clinical Molecular Biology (SIBioC) on the interference of haemolysis on five routine blood coagulation tests by evaluation of 269 paired haemolysed/non-haemolysed samples.

Biochem Med (Zagreb) 2018 Oct;28(3):030711

Section of Clinical Biochemistry, University of Verona, Verona, Italy.

Introduction: Haemolysis is the leading cause of sample rejection in laboratory haemostasis. Most studies focused on artificially haemolysed samples. The aim of this study was a prospective assessment of spontaneous haemolysis on haemostasis tests, by comparing results of haemolysed (H) new, non-haemolysed (NH) specimens, collected within 4hrs. As new coagulometers can identify interfering substances, visual assessment of haemolysis was also compared with instrumental haemolysis index and stratified in subclasses.

Materials And Methods: Two hundred and sixty nine paired samples were collected and analysed using ACL TOP750-CTS (Instrumentation Laboratory, Bedford, USA), for prothrombin time (PT), activated partial thromboplastin time (aPTT), D-Dimer (DD), fibrinogen (Fib) and antithrombin (AT). Bias between H and NH was calculated and compared with the respective critical difference (CD).

Results: Mean bias was - 0.1 s for PT (P = 0.057), - 1.1 s for aPTT (P < 0.001), 1025 ng/mL for DD (P < 0.001), - 0.04 g/L for Fib (P = 0.258) and 1.4% for AT (P = 0.013). Bias exceeding the CD varied according to the method, with larger differences for aPTT (36.1%) and DD (17.1%) and < 8% for PT, Fib and AT. No correlation emerged between free haemoglobin values and difference in haemostasis tests in H and NH samples for any tests. Moderate/severe haemolysis involved > 95% of samples. The agreement between visual assessment and instrumental evaluation of haemolysis was 0.62.

Conclusion: Spurious haemolysis deeply influences aPTT and DD, and to a lesser extent AT and Fib. Prothrombin time seems only slightly influenced, suggesting that PT can be accepted also in haemolysed samples. Although a good inter-observer correlation of haemolysis evaluation was found, the instrumental assessment of haemolysis seems recommendable.
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http://dx.doi.org/10.11613/BM.2018.030711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214687PMC
October 2018

Lipoprotein-associated phospholipase A2 predicts cardiovascular events in dialyzed patients.

J Nephrol 2019 Apr 27;32(2):283-288. Epub 2018 Aug 27.

Department of Health Sciences, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.

Background: Lipoprotein-associated phospholipase A (Lp-PLA) is a serine lipase that enhances the instability of the atherosclerotic plaques. While in the general and cardiac population Lp-PLA is recognized as an important determinant of cardiovascular (CV) accidents, no data are available for the renal population. The aim of this study was to evaluate the relationship between Lp-PLA2 and acute CV events in hemodialyzed patients.

Methods: We enrolled 102 dialyzed patients, 63% male, age 71 years (59-78), 35% with diabetes, 54% hypertension, 40% coronary artery disease and 31% peripheral vascular disease. They were investigated for Lp-PLA2 (cut-off < 194 nmol/min/ml), lipoprotein profile and the occurrence of acute CV events and death in the subsequent 3 years of follow-up.

Results: The median (interquartile ranges) levels of Lp-PLA2, total-, HDL-, LDL-cholesterol and ApoB/ApoA lipoprotein ratio were 184.5 (156.5-214.5) nmol/min/ml, 158 (127-191) mg/dl, 41 (33-51) mg/dl, 79 (63-102) mg/dl and 0.72 (0.58-0.89), respectively. In 42% of patients, Lp-PLA2 was > 194 nmol/min/ml and total- and LDL-cholesterol were higher, as well as CV morbidity and mortality. During follow-up, 51% of patients developed at least one CV event; the median survival time was 36 months, with a total and CV mortality of 42 and 29%, respectively. At multivariate Cox regression, Lp-PLA2 > 194 nmol/min/ml (HR = 2.98, p = 0.005), age (HR = 1.03, p = 0.029), diabetes (HR = 2.86, p = 0.002) and hypertension (HR = 2.93, p = 0.002) were independently associated with time to CV events.

Conclusions: Lp-PLA2 activity is elevated among dialyzed patients and is an independent risk factor for acute CV events in a mean follow-up of 3 years.
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http://dx.doi.org/10.1007/s40620-018-0521-3DOI Listing
April 2019

A Real-World Setting Study: Which Glucose Meter Could Be the Best for POCT Use? An Easy and Applicable Protocol During the Hospital Routine.

J Diabetes Sci Technol 2018 09 22;12(5):1053-1060. Epub 2018 May 22.

2 ASUR MARCHE AV2, O.U. Clinical Pathology, Via Cellini, 1, Senigallia (AN), Italy.

The aim of this retrospective study is to evaluate the reliability and robustness of six glucose meters for point-of-care testing in our wards using a brand-new protocol. During a 30-days study period a total of 50 diabetes patients were subjected to venous blood sampling and glucose meter blood analysis. The results of six glucose meters were compared with our laboratory reference assay. GlucoMen Plus (Menarini) with the 82% of acceptable results was the most robust glucose meter. Even if the Passing-Bablok analysis demonstrates the presence of constant systematic errors and the Bland-Altman test highlighted a possible overestimation, the surveillance error grid analysis showed that this glucose meter can be used safely. We proved that portable glucose meters are not always reliable in routinely clinical settings.
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http://dx.doi.org/10.1177/1932296818774077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6134620PMC
September 2018

Erythroblastaemia in natalizumab-treated patients with multiple sclerosis.

Mult Scler Relat Disord 2016 Jul 2;8:141-4. Epub 2016 Jun 2.

Clinical Chemistry Laboratory, Hospital Papa Giovanni XXIII, Piazza OMS 1, 24127 Bergamo, Italy. Electronic address:

Background: Natalizumab is a monoclonal antibody that significantly reduces the occurrence of relapses in relapse-remitting multiple sclerosis (RRMS) patients. Early papers on the clinical use of natalizumab in RRMS patients reported erythroblastemia as occasional and transient.

Objectives: to determine the prevalence and absolute count of erythroblasts (nucleated red blood cells, NRBCs) in peripheral blood of RRMS patients in different treatment groups and healthy controls from the same geographic area using the same equipment for laboratory analysis.

Methods: We retrospectively evaluated the samples of 203 consecutive RRMS patients including 26 subjects on natalizumab, 17 on fingolimod, 72 on interferon, 41 on glatiramer acetate, 47 treatment-naïve and 240 healthy controls from the same geographic area. Blood samples were processed using an XN-9000-Hematology Analyzer and subsequent microscopic verification. In the natalizumab-treated patients we performed an additional analysis in order to detect the expression of CD34+ cells in peripheral blood, as confirmation of a bone marrow mobilization.

Results: The prevalence of patients with NRBCs positivity was significantly higher in natalizumab-treated patients (92%) compared with the other treatment groups and healthy controls (0%) (p<0.0005). The median absolute NRBCs count was significantly higher in natalizumab-treated patients (median 0.020, p<0.0005) than in the other treatment groups and healthy controls. Natalizumab-treated patients also had higher levels of white blood cells than all other groups and lower haemoglobin levels than healthy subjects (p<0.01), but no morphologic alterations were evident at a subsequent review of red blood cells, platelets and white blood cells. CD34+ cells levels were consistent with mobilization of haematopoietic stem cells from the bone marrow (median 8 cells/µL, IQR 5-12).

Conclusions: We confirm erythroblastaemia as a frequent finding of natalizumab treatment in RRMS patients. More extended knowledge and adequate long-term observation of this phenomenon are essential to better understand any pathological implication.
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http://dx.doi.org/10.1016/j.msard.2016.05.020DOI Listing
July 2016

Polymorphisms Associated with Increased Cardiovascular Risk in the General Population do not Predict Acute Events in Hemodialysis Patients.

Clin Lab 2016 ;62(4):639-44

Background: Cardiovascular diseases are the leading cause of morbidity and mortality in hemodialysis patients (HP). The aim of the study was to analyze a series of polymorphisms (known to be associated with increased cardiovascular risk in the general population) in HP, in order to better understand the mechanisms of cardiovascular disease and to find new prevention strategies.

Methods: 102 hemodialysis patients were investigated for polymorphisms associated with increased cardiovascular risk in unselected population (FV Leiden R506Q; FV H1299R; FII G20210A; PAI-1 var 4G/5G; GpIIIA T1565C; FXIII var G/T; β-FIBRINOGENO var G/A; ACE I/D; AGT var M/T; ATR-1A1166C; APOE T112C; APOE T158C; MTHFR C677T; MTHFR A1298C; CBS 844ins68).

Results: No difference was observed in the prevalence of the analysed polymorphisms between HP and Caucasian unselected population, with the exception of FV H1299R, PAI-1 (4G/5G), and Factor XIII V34L, which were significantly higher in HP. However none of the genetic factors analysed was associated in HP with the cardiovascular events (non-fatal and fatal) recorded at the time of recruitment or during the eighteen months -follow up.

Conclusions: In HP, the traditional genetic risk factors for cardiovascular disease are not able to predict acute cardiac events, peripheral vascular events, and cerebral vascular events recorded during a follow up period of eighteen months.
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http://dx.doi.org/10.7754/clin.lab.2015.150813DOI Listing
June 2016

"Real life use" of troponin in the emergency department: a survey of over 3000 cases.

Biochem Med (Zagreb) 2015 15;25(3):421-9. Epub 2015 Oct 15.

Dipartimento di Medicina Traslazionale, Universitŕ del Piemonte Orientale, Novara, Italy ; Medicina e Chirurgia d'Accettazione e d'Urgenza, Azienda Ospedaliero-Universitaria Maggiore della Caritŕ, Novara, Italy.

Introduction: The aim of this study was to identify clinical variables which may be independently associated with positivity of a cardiac troponin I (cTnI) assay in a large population of patients admitted to the emergency department (ED).

Materials And Methods: 3166 subjects, with at least two troponin I tests ordered within 6 hours in the ED, were studied. Patient data were statistically analyzed to identify clinical associations with increased values of Troponin I.

Results: Although patients with diagnosis of acute coronary syndrome displayed troponin I values significantly higher than those of other groups, positivity to troponin I (>40 ng/L) was also observed in patients with other clinical conditions. In multivariate analysis, age, elevated heart rate and electrocardiographic changes were independently associated with troponin I positivity at admission. In the whole study population troponin I positivity exhibited high sensitivity and negative predictive value, counterbalanced by low specificity and limited positive predictive value.

Conclusions: Troponin I positivity should be combined with history and clinical evaluation and cautiously interpreted in the ED, especially in patients exhibiting factors associated with higher troponin I levels such as older age, elevated heart rate or ECG changes.
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http://dx.doi.org/10.11613/BM.2015.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4622198PMC
December 2015

Usefulness of suPAR in the risk stratification of patients with sepsis admitted to the emergency department.

Intern Emerg Med 2015 Sep 9;10(6):725-30. Epub 2015 Jul 9.

Emergency Department, SS. Antonio e Biagio e Cesare Arrigo Hospital, Via Venezia 16, 15100, Alessandria, Italy,

To investigate the role of suPAR in patients with sepsis admitted to the Emergency Department (ED). We performed multicentre prospective trial including patients admitted to the ED of three different Italian hospitals. Patients were studied upon admission on day 1, 2, 4 and 7. They were subdivided into two groups: sepsis (group 1) and severe sepsis or septic shock (group 2). The two groups were comparable for age, gender and CRP level on day 1. Patients with severe sepsis or septic shock displayed significantly higher baseline levels of suPAR, PCT and lactate. In both groups, suPAR decreased across the time (p < 0.0005). Group 1 was not different from group 2 (p = 0.545) in mortality at 7 days, while group 2 had higher mortality at 30 days than group 1 (p = 0.022). At the multivariate analysis, lactate1 (p = 0.012) and age (p = 0.019) were independent predictors of mortality at 7 days, whereas suPAR1 (p = 0.023) and age (p = 0.032) were independent predictors of mortality at 30 days. Lactate and suPAR resulted the most predictive biomarkers in the risk stratification of patients with suspected infection initially admitted to the ED, according to their role in predicting 7- and 30-day mortality, respectively.
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http://dx.doi.org/10.1007/s11739-015-1268-7DOI Listing
September 2015

High Prevalence of Vitamin D Deficiency in Native versus Migrant Mothers and Newborns in the North of Italy: A Call to Act with a Stronger Prevention Program.

PLoS One 2015 11;10(6):e0129586. Epub 2015 Jun 11.

Division of Pediatrics, Department of Health Sciences, University of "Piemonte Orientale Amedeo Avogadro", Novara, Italy; IRCAD (Interdisciplinary Research Center of Autoimmune Diseases), Novara, Italy.

Background: Vitamin D status during pregnancy is related to neonatal vitamin D status. Vitamin D deficiency has been associated with an increased risk of rickets in children and osteomalacia in adults. Aim of this study was to investigate 25OHD levels in maternal serum and in neonatal blood spots in native and migrant populations living in Novara (North Italy, 45°N latitude).

Methods And Findings: We carried out a cross sectional study from April 1st 2012 to March 30th 2013, in a tertiary Care Center. Maternal blood samples after delivery and newborns' blood spots were analyzed for 25OHD levels in 533 pairs. Maternal country of origin, skin phototype, vitamin D dietary intake and supplementation during pregnancy were recorded. Multivariate regression analysis, showed a link between neonatal and maternal 25OHD levels (R-square:0.664). Severely deficient 25OHD values (<25 nmol/L) were found in 38% of Italian and in 76.2% of migrant's newborns (p <0.0001), and in 18% of Italian and 48,4% of migrant mothers (p <0.0001) while 25OHD deficiency (≥25 and <50 nmol/L) was shown in 40.1% of Italian and 21.7% of migrant's newborns (p <0.0001), and in 43.6% of Italian and 41.3% of migrant mothers (p <0.0001). Italian newborns and mothers had higher 25OHD levels (34.4±19.2 and 44.9±21.2 nmol/L) than migrants (17.7±13.7 and 29.7±16.5 nmol/L; p<0.0001). A linear decrease of 25OHD levels was found with increasing skin pigmentation (phototype I 42.1 ±18.2 vs phototype VI 17.9±10.1 nmol/l; p<0.0001). Vitamin D supplementation resulted in higher 25OHD values both in mothers and in their newborns (p<0.0001).

Conclusions: Vitamin D insufficiency in pregnancy and in newborns is frequent especially among migrants. A prevention program in Piedmont should urgently be considered and people identified as being at risk should be closely monitored. Vitamin D supplementation should be taken into account when considering a preventative health care policy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0129586PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4466139PMC
May 2016

Vitamin D levels at birth and risk of type 1 diabetes in childhood: a case-control study.

Acta Diabetol 2015 Dec 28;52(6):1077-81. Epub 2015 May 28.

Department of Medical Sciences, University of Turin, Corso Dogliotti 14, 10126, Turin, Italy.

Aims: To assess whether vitamin D levels at birth were associated with risk of having type 1 diabetes up to 10 years of age and the potential modifier effect of ethnic group.

Methods: The Piedmont Diabetes Registry and the Newborn Screening Regional data were linked to identify cases (n = 67 incident children aged ≤10 years at diabetes onset, 2002-2012) and up to five controls (n = 236) matched for birthday and ethnic group. Cards with neonatal blood spot were used and 25-hydroxyvitamin D(3) assessed with tandem mass spectroscopy.

Results: In conditional logistic regression, OR for unit increment of log vitamin D was 0.78 (95 % CI 0.56-1.10). Vitamin D was significantly lower in migrant than in Italian control newborn babies (p < 0.0001), and interaction between vitamin D and migrant status was statistically significant (p = 0.04). Compared to migrant newborns babies with vitamin D ≥ 2.14 ng/ml, migrants with lower levels had an OR of 14.02 (1.76-111.70), whereas no association was evident in Italians.

Conclusions: Our case-control study within the Piedmont Diabetes Registry showed no association between vitamin D levels at birth and risk of having type 1 diabetes up to 10 years of age, apart from the subgroup of migrant babies, which might have clinical implications if confirmed.
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http://dx.doi.org/10.1007/s00592-015-0772-6DOI Listing
December 2015

Lipoprotein profile, lipoprotein-associated phospholipase A2 and cardiovascular risk in hemodialysis patients.

J Nephrol 2015 Dec 14;28(6):749-55. Epub 2015 May 14.

Clinical Chemistry Laboratory, Department of Health Sciences, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.

Background: Cardiovascular disease is the leading cause of morbidity and mortality in hemodialysis patients; the increased risk of cardiovascular disease is due to accelerated atherosclerosis, inflammation and impaired lipoprotein metabolism. We aimed to evaluate lipoprotein-associated phospholipase A2 (Lp-PLA2) and some pro-inflammatory aspects of the lipoprotein profile in dialyzed patients in order to evaluate the relationship with the accelerated atherosclerosis and vascular accidents.

Methods: In 102 dialysis patients and 40 non-uremic controls, we investigated the lipoprotein plasma profile, high sensitivity C-reactive protein (CRP), ceruloplasmin and serum amyloid A protein (SAA), and followed patients for 1 year to analyze the risk of acute cardiovascular events.

Results: Total cholesterol, low-density lipoprotein and high-density lipoprotein plasma levels were significantly lower in uremic patients than controls, whereas CRP, SAA, ceruloplasmin, Lp-PLA2 and their ratio with apolipoprotein A1 were significantly higher. Patients with Lp-PLA2 levels >194 nmol/min/ml had more acute cardiovascular events than patients with lower values.

Conclusion: Our results show that in dialysis subjects: (1) low-density lipoproteins show a more atherogenic phenotype than in the general population; (2) high-density lipoproteins are less anti-inflammatory; (3) Lp-PLA2 could potentially be used to evaluate cardiovascular risk.
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http://dx.doi.org/10.1007/s40620-015-0194-0DOI Listing
December 2015

Oligonucleotide Array-based Comparative Genomic Hybridization Approach in Hematologic Malignancies With Normal/Failed Conventional Cytogenetics and Fluorescent In Situ Hybridization.

Appl Immunohistochem Mol Morphol 2016 Feb;24(2):120-7

*Pathology Unit, Department of Translational Medicine ‡Department of Medical Sciences §Oncology Unit, Department of Translational Medicine, Amedeo Avogadro University, Novara †Cytogenetics Unit, San Giovanni Battista Hospital, Turin, Italy.

Oligonucleotide array-based comparative genomic hybridization (oaCGH) was used to investigate 60 cases of hematologic malignancies, mainly acute myeloid leukemias and myelodysplastic syndromes, in order to evaluate its sensitivity and specificity and to search for genomic alterations undetected by previous investigation with conventional cytogenetics (CC) and fluorescent in situ hybridization (FISH). On the basis of CC and FISH results, we subdivided the series into group A (36 cases with a normal karyotype after CC and/or FISH testing) and group B (24 cases with anomalies detected by CC and/or FISH). oaCGH did not show alterations in 21 cases of the group A (58.3%); in the remaining 15 cases (41.7%), it detected 19 new abnormalities (14 amplifications and 5 deletions). In the group B, oaCGH confirmed 32/55 aneuploidies detected by FISH (58.1%). The sensitivity increased at 27/33 confirmed aneuploidies (81.8%) by placing as a cutoff a mosaic of 50%. Moreover, in the cases of this group oaCGH revealed 36 new alterations (15 amplifications and 21 deletions). From these results it is possible to assess a strong overlap between results obtained by FISH and oaCGH. However, oaCGH is a reliable alternative where CC and FISH are not feasible and is able to identify new alterations unexplored by FISH.
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http://dx.doi.org/10.1097/PAI.0000000000000159DOI Listing
February 2016

A comparison between serum carbohydrate-deficient transferrin and hair ethyl glucuronide in detecting chronic alcohol consumption in routine.

Alcohol Alcohol 2015 May 19;50(3):266-70. Epub 2015 Feb 19.

Department of Medical Sciences, University 'Amedeo Avogadro' of Eastern Piedmont, Novara, Italy Clinical Chemistry Unit, Maggiore della Carità Hospital, Novara, Italy

Aims: In heavy alcohol consumption laboratory tests represent an objective evidence. In this study we compared older and newer biomarkers in blood and in hair.

Methods: Carbohydrate-deficient transferrin (CDT), ethyl glucuronide (EtG), AST, ALT, GGT, MCV were measured in a large sample (n = 562). All people declared no alcohol consumption within the last 3 months. Serum CDT was measured by the candidate HPLC reference method and expressed as relative amount of disialotransferrin (%DST: cutoff 1.7%). EtG was measured in hair by a validated in-house method by LC-MS/MS (cutoff 30 pg/mg).

Results: Respectively, 42 (7.5%) and 76 (13.5%) subjects were positive to CDT and EtG. In particular, 30 (5.3%) subjects were positive to both tests, 12 (2.1%) only to CDT, while 46 (8.2%) only to EtG. The agreement (positive and negative pairs) between CDT and EtG was 89.7%. Interestingly, 6 out of 12 (50%) CDT-positive subjects had EtG < 15 pg/mg, whereas 27 out of 46 (59%) EtG-positive subjects had CDT < 1.1%. Forty-one out of 76 (54%) EtG-positive subjects display EtG values within 30-50 pg/mg.

Conclusion: Large variability exists between CDT and EtG in detecting chronic alcohol consumption. We suggest to use CDT, or a combination of different biomarkers, to identify alcohol abuse in a forensic context. EtG results close to the cutoff (30-50 pg/mg) should be cautiously considered before any sanction is assigned.
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http://dx.doi.org/10.1093/alcalc/agv005DOI Listing
May 2015

Routine coagulation tests are not useful as a screening tool for the FII G20210A polymorphism.

Clin Lab 2014 ;60(10):1725-33

Background: The identification of prothrombin G20210A polymorphism (PT20210) is normally included in the thrombophilia laboratory panel and evaluated by DNA-based molecular analysis. To date, a routine coagulation test that helps to identify PT20210 carriers has not been set, in contrast to the FV Leiden mutation, for which a functional coagulation test, the Activated Protein C Resistance test (APCR), is available as a screening tool. More- over the molecular tests are expensive and are used inappropriately. The aim of the study is to characterize the effects of the prothrombin G20210A mutation on routine clotting assays in order to identify, if any, coagulation tests that can be used as a first-line cost-effective assay for prothrombin G20210A polymorphism.

Methods: Our cohort consisted of 80 PT20210 polymorphism carriers and 82 age and gender matched controls. All subjects were investigated for PT-INR, aPTT, dRVVT, FII (%), and Endogenous Thrombin Potential (EPT) parameters.

Results: In heterozygotes and wild-type, PT, aPTT, and dRVVT values were not significantly different. The plasma activity of Factor II (%), AUC TG (%), and C max (%) of EPT were significantly higher in heterozygotes than in controls (p < 0.0001, Mann-Whitney test). In the absence of oral anticoagulant therapy and/or heparin, lupus anticoagulants, and liver disease, the discriminating abilities of the FII, AUC TG, and C max (%) to separate properly the study population into carriers and controls were equal to 0.99 (95% CI 0.98 to 1.00); 0.97 (95% CI 0.94 to 0.99), and 0.84 (95% CI 0.77 to 0.90), respectively.

Conclusions: All routine clotting assays performed in the present work are not useful as a screening tool for the G20210A prothrombin gene allele in a general population. Definitely, to date, the exclusive possible approach to identify the PT20210 mutation is molecular genetic testing, but unfortunately it is used inappropriately, contributing significantly to an uncontrolled waste of resources. It is mandatory to restrict the genetic thrombophilia test ordering to when it is actually recommended by the guidelines and to educate clinicians on the waste and danger of over-testing, particularly genetic tests, taking into account the fact that the PT20210 polymorphism is extremely variable (0.7 to 8% in Europe; 1.3-5% in the USA).
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http://dx.doi.org/10.7754/clin.lab.2014.140215DOI Listing
March 2015

CYP2E1 autoantibodies in liver diseases.

Redox Biol 2014 18;3:72-8. Epub 2014 Nov 18.

Department of Health Sciences, University "Amedeo Avogadro" of East Piedmont and Interdepartmental Research Centre for Autoimmune Diseases (IRCAD), Novara, Italy. Electronic address:

Autoimmune reactions involving cytochrome P4502E1 (CYP2E1) are a feature of idiosyncratic liver injury induced by halogenated hydrocarbons and isoniazid, but are also detectable in about one third of the patients with advanced alcoholic liver disease (ALD) and chronic hepatitis C (CHC). In these latter the presence of anti-CYP2E1 auto-antibodies is an independent predictor of extensive necro-inflammation and fibrosis and worsens the recurrence of hepatitis following liver transplantation, indicating that CYP2E1-directed autoimmunity can contribute to hepatic injury. The molecular characterization of the antigens recognized by anti-CYP2E1 auto-antibodies in ALD and CHC has shown that the targeted conformational epitopes are located in close proximity on the molecular surface. Furthermore, these epitopes can be recognized on CYP2E1 expressed on hepatocyte plasma membranes where they can trigger antibody-mediated cytotoxicity. This does not exclude that T cell-mediated responses against CYP2E1 might also be involved in causing hepatocyte damage. CYP2E1 structural modifications by reactive metabolites and molecular mimicry represent important factors in the breaking of self-tolerance against CYP2E1 in, respectively, ALD and CHC. However, genetic or acquired interferences with the mechanisms controlling the homeostasis of the immune system are also likely to contribute. More studies are needed to better characterize the impact of anti-CYP2E1 autoimmunity in liver diseases particularly in relation to the fact that common metabolic alterations such as obesity and diabetes stimulates hepatic CYP2E1 expression.
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http://dx.doi.org/10.1016/j.redox.2014.11.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4297929PMC
August 2015