Fabrizio Cappellini

Normal Fasting Plasma Glucose and Risk of Type 2 Diabetes

OBJECTIVE To investigate the association of normal fasting plasma glucose (FPG) and the risk for type 2 diabetes. RESEARCH DESIGN AND METHODS Data concerning 13,845 subjects, aged 40–69 years, who had their FPG measured at least three times between 1992 and 2008 were extracted from a database. Three FPG groups were defined (51–82, 83–90, and 91–99 mg/dL). A Cox proportional hazards analysis was applied to estimate the risk of incident diabetes adjusted for other risk factors. RESULTS During 108,061 person-years of follow-up (8,110 women and 5,735 men), 307 incident cases of type 2 diabetes were found. The final model demonstrated a hazard ratio of 2.03 (95% CI 1.18–3.50) for 91–99 mg/dL and 1.42 (0.42–4.74) for 83–90 mg/dL. CONCLUSIONS Our data suggest that FPG between 91 and 99 mg/dL is a strong independent predictor of type 2 diabetes and should be used to identify people to be further investigated and aided with preventive measures.

Iron Stores, Hepcidin, and Aortic Stiffness in Individuals with Hypertension.

Background & Aims Iron accumulation within the arterial wall has been hypothesized to promote atherosclerosis progression. Aim of this study was to evaluate whether the hormone hepcidin and iron stores are associated with arterial stiffness in subjects with essential hypertension. Methods Circulating hepcidin, ferritin, and mutations in the hemochromatosis gene were compared between subjects included in the first vs. third tertile (n=284 each) of carotid-femoral pulse wave velocity (PWV) in an unselected cohort of patients with arterial hypertension. Results At univariate logistic regression analysis, high PWV was associated with higher ferritin levels (p=0.010), but lower hepcidin (p=0.045), and hepcidin ferritin/ratio (p<0.001). Hemochromatosis mutations predisposing to iron overload were associated with high PWV (p=0.025). At multivariate logistic regression analysis, high aortic stiffness was associated with older age, male sex, lower BMI, higher systolic blood pressure and heart rate, hyperferritinemia (OR 2.05, 95% c.i. 1.11-3.17 per log ng/ml; p=0.022), and lower circulating hepcidin concentration (OR 0.29, 95% c.i. 0.16-0.51 per log ng/ml; p<0.001). In subgroup analyses, high PWV was associated with indices of target organ damage, including micro-albuminuria (n=125, p=0.038), lower ejection fraction (n=175, p=0.031), cardiac diastolic dysfunction (p=0.004), and lower S wave peak systolic velocity (p<0.001). Ferritin was associated with cardiac diastolic dysfunction, independently of confounders (p=0.006). Conclusions In conclusion, hyperferritinemia is associated with high aortic stiffness and cardiac diastolic dysfunction, while low circulating hepcidin with high aortic stiffness.

Heart-type fatty acid-binding protein may exclude acute myocardial infarction on admission to emergency department for chest pain

Abstract Chest pain is one of the most frequent reasons for presentation to the emergency department (ED), although the estimated prevalence of AMI (acute myocardial infarction) in the ED is about 4%. One criterion for diagnosis of AMI is the demonstration of a rise and/or fall in cardiac troponins, but time is needed for this to happen. Thus, the use of an additional ‘early marker’ of cardiac injury may aid to exclude AMI rapidly. The aim of the study was to evaluate the possibility of excluding AMI with the determination of heart-type fatty acid-binding protein (H-FABP) on baseline samples of patients referring to the ED for chest pain. 26 AMI patients and 41 non-AMI comparisons were included in the study. Both H-FABP and high sensitivity cardiac troponin T (hs-cTnT) were measured in baseline samples from these subjects. H-FABP had a negative predictive value of 100%, thus indicating the possibility of its usage in a rule-out strategy for AMI in ED for patients presenting with chest pain.

Feto-maternal correlation of PTX3, sFlt-1 and PlGF in physiological and pre-eclamptic pregnancies

Objective: PTX3, sFlt-1 and PlGF levels in maternal blood are altered in some obstetric diseases, such as preeclampsia (PE). Nonetheless, only few data on their expression in the fetal compartment have been reported so far. Study Design: An observational study was performed by prospectively collecting maternal and fetal serum samples in 51 singleton pregnancies divided into two groups: 22 PE women and 29 healthy controls. The relationships between maternal and fetal marker serum levels were evaluated by Spearman correlation. Results: A feto-maternal correlation was neither identified for PTX3 in either PE or control groups (1.1 versus 3.8 ng/ml, p = 0.17 and 0.9 versus 1.3 ng/ml, p = 0.30, respectively), nor for sFlt-1 and PlGF in healthy pregnancies (158.2 versus 3326.0 pg/ml, p = 0.28 and 11.0 versus 230.9 pg/ml, p = 0.51). In contrast, PE patients showed a significant positive feto-maternal correlation for both sFlt-1 and PlGF (324.1 versus 10 825.0 pg/ml and 7.8 versus 31.6 pg/ml, respectively, p = 0.02 for both markers). Conclusion: According to our results, an independent fetal production of the analyzed soluble angiogenic markers can be hypothesized in pregnancies complicated by PE.

Verification of an immunoturbidimetric assay for heart-type fatty acid-binding protein (H-FABP) on a clinical chemistry platform and establishment of the upper reference limit.

BACKGROUND Heart-type fatty acid-binding protein (H-FABP) is an early biomarker of cardiac injury. Randox Laboratories developed an immunoturbidimetric H-FABP assay for non-proprietary automated clinical chemistry analysers that could be useful in the emergency department. We verified the analytical performances claimed by Randox Laboratories on Roche Cobas 6000 clinical chemistry platform in use in our laboratory, and we defined our own 99th percentile upper reference limit for H-FABP. METHODS For the verification of method performances, we used pools of spared patient samples from routine and two levels of quality control material, while samples for the reference value study were collected from 545 blood donors. Following CLSI guidelines we verified limit of blank (LOB), limit of detection (LOD), limit of quantitation (LOQ), repeatability and within-laboratory precision, trueness, linearity, and the stability of H-FABP in EDTA over 24h. RESULTS AND DISCUSSION The LOQ (3.19 μg/L) was verified with a CV% of 10.4. The precision was verified for the low (mean 5.88 μg/L, CV=6.7%), the medium (mean 45.28 μg/L, CV=3.0%), and the high concentration (mean 88.81 μg/L, CV=4.0%). The trueness was verified as well as the linearity over the indicated measurement interval of 0.747-120 μg/L. The H-FABP in EDTA samples is stable throughout 24h both at room temperature and at 4 °C. The H-FABP 99th percentile upper reference limit for all subjects (3.60 μg/L, 95% CI 3.51-3.77) is more appropriate than gender-specific ones that are not statistically different.

IgMκ-IgMλ pair quantitation in the clinical laboratory practice

BACKGROUND New Hevylite® assay quantifies the immunoglobulin classes, including IgM bound to light chains, allowing distinguishing immunoglobulins involved and uninvolved in plasma cell disorders. OBJECTIVE To compare data obtained by IgM Hevylite® (IgM-HLC) assay with conventional methods used in routine laboratory practice for monitoring IgM plasma cell disorders. METHODS Serum samples (n=122) from 50 patients with IgM monoclonal protein (MP) identified by Immunofixation (IFE) before the beginning of the study were collected during monitoring from December 2012 to September 2014 (2 Waldestroms macroglobulinemia, 4 NH-lymphoma, 44 MGUS) and were assessed using IgM Hevylite® (HLC) assay, Capillary Electrophoresis (CE), Immunofixation (IFE), serum Free Light Chain (FLC) assay and total IgM measurements. RESULTS IgM MP was detected by IFE in 85/122 samples (71 IgMk, 10 IgMl, 4 IgMk/IgMl), while in 37/122 was undetectable although CE measured small MP, probably as a consequence of disease stimulating inflammatory immuno-response. Among the 85 positive samples, the HLC ratio but not the FLC ratio was altered in 36 samples while in 4 sera only FLC was altered. Out of 37 IFE negative samples 24 had normal HLC and FLC ratios. CONCLUSIONS Since the partial overlap of abnormalities identified by HLC and FLC assays, IgM Hevylite assay can provide valuable information on the evolution of IgM monoclonal disease and may support the recognition of a transitory monoclonality leading to an improvement in routine laboratory practice.

The development of autoverification rules applied to urinalysis performed on the AutionMAX-SediMAX platform

BACKGROUND Fully automated urine analyzers integrated with expert software can help to select samples that need review in routine clinical laboratory. This study aimed to define review rules to be set in the expert software Director for routine urinalysis on the AutionMAX-SediMAX platform. METHODS A set of 1002 urinalysis data randomly extracted from the daily routine was used. The blind on-screen assessment was used as a reference. The data set was used to optimize the standard rules preset in the software to establish review criteria useful to intercept automated microscopy misidentification and particles suggestive of clinically significant profile. The review rate was calculated. The rules-set was also evaluated for the selection of clinically significant samples. RESULTS The review rules established were cross-checked between AutionMAX and SediMAX parameters, element reporting by SediMAX and strip results. For the complete rules-set the review rate was 47.6% and the efficiency for clinically significant sample selection was 58%. Finally, on the basis of the review rules an algorithm for routine practice was created. CONCLUSIONS Review rules applied to the algorithm for routine practice enhance workflow efficiency and optimize sample screening. Revision is not necessary for samples not flagged by the rules.