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Mauro Panteghini

Publications and source records attributed to Mauro Panteghini.

At least 19 recordsLinked to original sources
PubMed2006

Toward standardization of cardiac troponin I measurements part II: assessing commutability of candidate reference materials and harmonization of cardiac troponin I assays.

BACKGROUND: Cardiac tropoin I (cTnI) measurements show an approximately 20- to 40-fold difference between assays, and better standardization and harmonization are needed. Toward this goal, the AACC cTnI Standardization Committee collaborated with the National Institute of Standards and Technology (NIST) in an earlier study to select 2 candidate reference materials (cRMs). METHODS: Two troponin cRMs, a troponin C-troponin I-troponin T (CIT) complex from human heart tissue and a CIT complex from recombinant technology, were supplied to NIST for assessment of composition and purity, and cTnI value assignment. These cRMs and 6 cTnI-positive human serum pools were shipped to manufacturers of 15 cTnI assays. Commutability of the materials was examined by determining the numerical relationship for the cRM preparations between each manufacturer-specified field method and each of the other 14 field methods. These relationships were then compared with the corresponding numerical relationships for the human serum pools. Harmonization of methods was accomplished by determining regression parameters relative to the analytical system yielding values closest to the median for each serum pool. These regression parameters were used to recalculate pool values to harmonize the assays. Interassay CVs before and after harmonization were determined. RESULTS: Characterization of the CIT and CI cRMs showed that these materials were of specified composition. The proportion of cTnI methods that demonstrated commutability for the CIT cRM was 45%; for the CI cRM, 39% of methods demonstrated commutability. Interassay cTnI variability for the field methods ranged from 82% to 97%, median 88%. After harmonization, variability of the serum pools for the cTnI methods was decreased to between 9.0% and 23%, median 15.5%. CONCLUSIONS: The proportion of methods demonstrating commutability was too low for use as a common calibrator for the cTnI field methods. However a simple strategy using serum pools can improve harmonization of field cTnI methods by more than 5-fold. The CIT cRM was selected by the AACC cTnI standardization committee, and a new lot has been classified as the cTnI certified reference material Standard Reference Material 2921 by NIST.

Calibration↗
PubMed2006

Trueness verification and traceability assessment of results from commercial systems for measurement of six enzyme activities in serum: an international study in the EC4 framework of the Calibration 2000 project.

BACKGROUND: The in vitro diagnostics directive of the European Union requires traceability to higher order reference measurement procedures and materials for analytes in assuring the result trueness and comparability of laboratory measurements. Manufacturers must ensure that the systems they market are calibrated against available reference systems. Validation of metrologically traceable calibrations is, however, required. METHODS: A commutable serum-based material was analyzed in three reference laboratories and target values for six enzymes (ALT, AST, CK, GGT, LD, amylase) were assigned using IFCC reference measurement procedures. 70 laboratories in Germany, Italy, and The Netherlands measured the same enzymes in the material using procedures from six commercial companies. A system for maximum allowable error was developed from the biological variation model and the results of the various procedures were tested on their compliance to trueness and between-laboratory and within-laboratory variations relative to the maximum allowable. RESULTS: For ALT results were relatively good. >95% of laboratories using systems from Dade, Olympus, Ortho and Roche are expected to comply traceability within the biologically derived limits, and 94% respectively 89% from Abbott and Beckman. For AST and GGT only Dade respectively Olympus fully complied. For CK all companies showed significant bias. Nevertheless >95% of laboratories applying Abbott, Beckman and Roche systems will comply. Finally, LD and amylase measurements require significant improvement. Some manufacturers continue to sell on the European market assays giving results which are not traceable to the internationally accepted reference systems. CONCLUSIONS: The traceability of enzyme measurements obtained with routine procedures to internationally accepted IFCC reference systems is not yet satisfactorily accomplished in clinical practice.

Biomedical Research↗
PubMed2006

The importance of analytical quality specifications for biomarker assays currently used in acute cardiac care.

It is very important that cardiac biomarkers on which clinically relevant decisions will rest are measured with highly reliable assays. Adequate studies are needed before new methods can be implemented in the laboratory routine, and only well-documented assays should be considered for clinical use. Therefore, it is critical that, as new biomarkers are proposed, quality specifications are developed. Only after appropriate analytical quality specifications are addressed, the issues pertaining to methodological differences that result in non-harmonized concentration values, and clinical interpretation of biomarker concentrations will be reconciled. Today, the technology to address many analytic problems is at hand, but commitment on the part of manufacturers and their customers in the laboratory and clinical communities is essential. The design control loop is not closed until the finished in vitro diagnostic system is adequately validated to meet the customer needs, including analytical quality specifications. It is essential to determine the attributes and performance characteristics of relevant competitive systems and their degree of acceptance by clinical laboratories in order to demonstrate that user needs are definitely met. The responsibility of defining and implementing these issues must be a shared responsibility among laboratorians, clinicians, industry, and regulatory agencies on an international front. To date, two sets of quality specifications have been published, one for cardiac troponin assays and one for B-type natriuretic peptide assays. Both address analytical factors, such as calibrator characterization, antibody specificity, assay sensitivity and imprecision, and interferents, as well as preanalytical factors, such as sample type and stability. It would be ideal if regulatory agencies, such as FDA in the United States, accept these criteria for premarket approval clearance applications.

Biological Assay↗
PubMed2006

The importance of metrological traceability on the validity of creatinine measurement as an index of renal function.

The glomerular filtration rate (GFR) is currently considered the best overall index of kidney function. The possibility that laboratories might routinely report an estimated GFR has become practically feasible with the development of a formula, the "four-variable" Modification of Diet in Renal Disease study (MDRD) equation that uses age, sex, race, and serum creatinine parameters. However, a limitation of this equation for general implementation in healthcare is related to the use of differently calibrated creatinine measurement procedures among laboratories. The only way to achieve universal implementation of the GFR prediction equation, with the associated clinical benefits for patients, is, therefore, to promote worldwide standardization of methods to determine creatinine, together with the introduction of a revised GFR-estimating equation appropriate for use with standardized creatinine methods.

Carbon Radioisotopes↗
PubMed2006

[Biochemical markers for predicting chemotherapy-induced cardiotoxicity: systematic review of the literature and recommendations for use].

Chemotherapy is a well established therapeutic approach for several malignancies, but its clinical efficacy is often limited by related cardiotoxicity leading to cardiomyopathy evolving towards heart failure that may worsen the patient outcome. To detect cardiac damage, the most frequently adopted diagnostic approach is the estimation of left ventricular ejection fraction by echocardiography, showing, however, low sensitivity in early prediction of cardiomyopathy, when appropriate treatments could still improve the patient's outcome. Cardiospecific biomarkers, like cardiac troponins, show high diagnostic efficacy in the early, subclinical phase of disease, becoming positive approximately 3 months before clinical onset of cardiomyopathy. Furthermore, the increase in their concentrations is well correlated with the disease severity and may predict the occurrence of major cardiac events during follow-up. On the other hand, negative troponin concentrations may identify patients with a very low risk of cardiomyopathy (negative predictive value = 99%). For cardiac natriuretic peptides, definitive evidence about a diagnostic or prognostic role in predicting chemotherapy-induced cardiomyopathy is lacking and their practical use in this context cannot be recommended until their clinical efficacy is clearly defined.

Biomarkers↗
PubMed2005

Recommendations for improving serum creatinine measurement: a report from the Laboratory Working Group of the National Kidney Disease Education Program.

BACKGROUND: Reliable serum creatinine measurements in glomerular filtration rate (GFR) estimation are critical to ongoing global public health efforts to increase the diagnosis and treatment of chronic kidney disease (CKD). We present an overview of the commonly used methods for the determination of serum creatinine, method limitations, and method performance in conjunction with the development of analytical performance criteria. Available resources for standardization of serum creatinine measurement are discussed, and recommendations for measurement improvement are given. METHODS: The National Kidney Disease Education Program (NKDEP) Laboratory Working Group reviewed problems related to serum creatinine measurement for estimating GFR and prepared recommendations to standardize and improve creatinine measurement. RESULTS: The NKDEP Laboratory Working Group, in collaboration with international professional organizations, has developed a plan that enables standardization and improved accuracy (trueness) of serum creatinine measurements in clinical laboratories worldwide that includes the use of the estimating equation for GFR based on serum creatinine concentration that was developed from the Modification of Diet in Renal Disease (MDRD) study. CONCLUSIONS: The current variability in serum creatinine measurements renders all estimating equations for GFR, including the MDRD Study equation, less accurate in the normal and slightly increased range of serum creatinine concentrations [<133 micromol/L (1.5 mg/dL)], which is the relevant range for detecting CKD [<60 mL.min(-1).(1.73 m2)(-1)]. Many automated routine methods for serum creatinine measurement meet or exceed the required precision; therefore, reduction of analytical bias in creatinine assays is needed. Standardization of calibration does not correct for analytical interferences (nonspecificity bias). The bias and nonspecificity problems associated with some of the routine methods must be addressed.

Calibration↗
PubMed2005

The new definition of myocardial infarction and the impact of troponin determination on clinical practice.

OBJECTIVE: To discuss the more controversial clinical and laboratory aspects in the application of the new biochemical diagnostic standard for myocardial infarction, 4 years after its introduction, and to make some suggestions, which could allow for a more realistic application of the new definition in the current clinical practice. METHODS: Studies published in the last 4 years in the most important cardiology and laboratory medicine journals (including proceedings of the international meetings), discussing advantages and limits of the new definition of myocardial infarction, were reviewed and pertinent data were discussed and compared with similar information available in literature. RESULTS AND CONCLUSIONS: Although the exact status of implementation of the new definition of myocardial infarction cannot yet be known, the trend toward such recommendation is evolving significantly, even if at different rates in different countries. To make the transition smoother, major educational efforts are required to disseminate the conceptual reasoning behind the new guidelines. On the other hand, more knowledge is needed for some relevant issues, such as the different analytical performance of cardiac troponin assays or the prognostic significance of biomarker changes after a percutaneous coronary intervention.

Angioplasty, Balloon, Coronary↗
PubMed2005

Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome.

BACKGROUND: Evaluation of patients who present to the hospital with a complaint of chest pain or other signs or symptoms suggestive of acute coronary syndrome (ACS) is time-consuming, expensive, and problematic. Recent investigations have indicated that increases in biomarkers upstream from biomarkers of necrosis (cardiac troponins I and T), such as inflammatory cytokines, cellular adhesion molecules, acute-phase reactants, plaque destabilization and rupture biomarkers, biomarkers of ischemia, and biomarkers of myocardial stretch may provide earlier assessment of overall patient risk and aid in identifying patients with higher risk of an adverse event. APPROACH AND CONTENT: The purpose of this review is to provide an overview of the pathophysiology and clinical and analytical characteristics of several biomarkers that may have potential clinical utility to identify ACS patients. These biomarkers (myeloperoxidase, metalloproteinase-9, soluble CD40 ligand, pregnancy-associated plasma protein A, choline, ischemia-modified albumin, unbound free fatty acids, glycogen phosphorylase isoenzyme BB, and placental growth factor) have demonstrated promise and need to be more thoroughly evaluated for commercial development for implementation into routine clinical and laboratory practice. SUMMARY: Specifications that have been addressed for cardiac troponins and natriuretic peptides will need to be addressed with the same scrutiny for the biomarkers discussed in this review. They include validating analytical imprecision and detection limits, calibrator characterization, assay specificity and standardization, pre-analytical issues, and appropriate reference interval studies. Crossing boundaries from research to clinical application will require replication in multiple settings and experimental evidence supporting a pathophysiologic role and, ideally, interventional trials demonstrating that monitoring single or multiple biomarkers improves outcomes.

Acute Disease↗
PubMed2005

Quality specifications for B-type natriuretic peptide assays.

BACKGROUND: The objective of this report is to improve the quality of immunochemical measurements of B-type natriuretic peptide (BNP) and its N-terminal propeptide (NT-proBNP). The recommendations proposed are intended for use by manufacturers of commercial assays, by clinical laboratories using those assays, by clinical trial groups and research investigators, and by regulatory agencies, such as the United States Food and Drug Administration. METHODS: A group of cardiac biomarker experts reviewed and abstracted the scientific literature to provide recommendations pertaining to the quality specifications for BNP/NT-proBNP assays. RESULTS: The evidence-based recommendations encourage manufacturers to endorse and consistently follow the proposed recommendations; encourage that all package inserts for BNP/NT-proBNP immunoassays include uniform information on assay design, preanalytical performance characteristics, analytical performance characteristics, and clinical performance; and encourage regulatory agencies to adopt a minimal and uniform set of criteria for manufacturers to provide when seeking clearance for new and/or improved assays. CONCLUSIONS: These recommendations address the use of BNP and NT-proBNP as cardiac biomarkers and not their physiologic and/or pathophysiologic relevance.

Biomarkers↗
PubMed2005

Measurement of troponin I 48 h after admission as a tool to rule out impaired left ventricular function in patients with a first myocardial infarction.

Few studies have evaluated cardiac troponin I (cTnI) as a marker for infarct size and left ventricular (LV) dysfunction. Here we investigated the ability of a single-point cTnI, measured with a second-generation assay (Access AccuTnI), to estimate infarct size and assess LV function in patients with a first myocardial infarction (AMI). cTnI measurements were performed 12 and 48 h after admission in 63 consecutive AMI patients. LV function was evaluated by gated single-photon emission computed tomography (SPECT) and infarct size was estimated by CK-MB peak and SPECT myocardial perfusion. LV function and infarct size were evaluated by SPECT before hospital discharge. SPECT was also repeated 3 months later. Significant correlations (p<0.001) were found between cTnI at 12 and 48 h and both the peak CK-MB (r=0.61 and r=0.82, respectively) and the perfusion defect size at SPECT (r=0.55 and r=0.61, respectively). cTnI at 12 and 48 h were inversely related (p<0.001) to LV ejection fraction (LVEF) assessed both early (r=-0.45 and r=-0.57, respectively) and 3 months after AMI (r=-0.51 and r=-0.69, respectively). cTnI >14.8 microg/L at 48 h predicted an LVEF <40% at 3 months with a sensitivity of 100% [95% confidence interval (CI) 73.5-100%], specificity of 65% (CI 49-79%), and a negative predictive value of 100%. Our findings demonstrate that a single cTnI measurement 48 h after admission is useful for ruling out impaired LV function in a routine clinical setting.

Adult↗