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Mattiuzzi C.,Servizio Governance Clinica | Favaloro E.J.,Westmead Hospital
Seminars in Thrombosis and Hemostasis | Year: 2013

Thrombolytic therapy by infusion of analogs of tissue plasminogen activator (tPA), other recombinant-based plasminogen activators (e.g., alteplase, reteplase, and tenecteplase), streptokinase, and urokinase (uPA) aims to clear blood clots and restore blood flow in occluded blood vessels. Thrombolytic therapy is thereby frequently used in patients with myocardial infarction, stroke, peripheral arterial disease, and massive pulmonary embolism. The leading drawbacks of thrombolysis and associated therapy are represented by a significant burden of inefficacy combined with a high risk of bleeding complications. Recent advances in understanding the complex pathophysiology of vascular occlusions, combined with important technological innovations, are notably improving the therapeutic armamentarium against thrombotic and occlusive disorders. Most of the past and ongoing research in this area have entailed thrombus-targeted fibrinolytic therapy with either tissue- and fibrin-specific immunoconjugates, fibrinolytic-bearing erythrocytes, or fibrinolytic-bearing nanoparticles. The greatest advantages of thrombus-targeted fibrinolysis, especially with biocompatible nanoparticles, are represented by their preferential localization within developing clots, effectual thrombolysis and enhanced safety due to substantial reduction of the dosage of fibrinolytic agents, and reduced onstream adverse effects. These positive biological features, coupled with minimal extravasation and favorable clearance from the circulation, appear advantageous for obtaining more efficacious and durable thrombolytic effects while concomitantly lowering or even eliminating the risk of systemic bleeding complications that typically accompany the injection of free or soluble plasminogen activators. Although an ideal technique has not been definitely established so far, tPA-bearing nanoparticles exhibiting affinity for clot-specific cells and biomolecules coupled with low-frequency ultrasound seem to bear the greatest advantages for prevention and therapy of acute thrombosis, with the possibility to specifically guide and concentrate the thrombolytic agent at the site of pathologic thrombi and clear preexisting clots by a series of mechanisms combining mechanical stress and increased penetration and effectiveness of the drugs employed. © 2013 by Thieme Medical Publishers, Inc.


Mattiuzzi C.,Servizio Governance Clinica | Comelli I.,Unita Operativa Pronto Soccorso e Medicina dUrgenza | Cervellin G.,Unita Operativa Pronto Soccorso e Medicina dUrgenza
Biochemia Medica | Year: 2013

Background: Early diagnosis is crucial for management of patients with suspected acute myocardial infarction (AMI). Among innovative and promising biomarkers, the recent interest raised on glycogen phosphorylase isoenzyme BB (GPBB) has prompted us to perform a meta-analysis of published studies. Materials and methods: A systematic electronic search was carried out on PubMed, Web of Science and Google Scholar, with no date restriction, to retrieve all articles that have investigated the early diagnostic performance of GPBB in patients with suspected AMI, and directly reported or allowed calculation of sensitivity and specificity. A meta-analysis of the reported sensitivity and specificity of each study and pooled area under the curve (AUC) was then performed by random effect approach. Heterogeneity was assessed by I-square statistics. Results: Eight studies were finally selected for analysis (941 subjects; 506 cases and 435 controls), with a high heterogeneity (I-squared, 86.3%). The resulting pooled estimates and 95% confidence interval were 0.854 (0.801-0.891) for sensitivity, 0.767 (0.713-0.815) for specificity, 0.826 (0.774--0.870) for negative predictive value, 0.802 (0.754-0.844) for positive predictive value, and 0.754 (0.602-0.907) for AUC. In those studies that have simultaneously assessed GPBB and a troponin immunoassay, the combination of these biomarkers did not significantly improve the performance of troponin alone. Conclusion: GPBB does not meet the current requirements for an efficient diagnosis of AMI when used as a stand-alone test, whereas its combination with troponin merits further investigation in larger trials.


Mattiuzzi C.,Servizio Governance Clinica
Rivista Italiana della Medicina di Laboratorio | Year: 2012

Background: There is now evidence that the advantages of screening for prostate cancer based only on prostate specific antigen (PSA) are probably offset by the health and economic disadvantages arising from over-diagnosis and over-treatment. Among novel and promising biomarkers, attention has recently been focused on the PSA isoform p2PSA, alone or in combination with free PSA (as %p2PSA), and in combination with total and free PSA as the prostate health index (phi). Methods: We performed an electronic search for original articles published in English, French, Spanish and Italian reporting studies that assessed the diagnostic performance of %p2PSA for prostate cancer screening in direct comparison with PSA, using the keywords "Prostate Cancer", and "Measurement" or "Screening", and "proPSA" or "p2PSA" or "[-2]proPSA". Titles, abstracts and full texts were carefully read, and articles not matching the inclusion criteria were excluded. Heterogeneity was evaluated by the I-squared test. The pooled estimates of accuracy and the resulting area under the receiver operator characteristic curve (AUC) were calculated using a random effect model. Results: On the basis of the electronic search, 11 articles and 12 studies, including a total of 5,139 subjects (2,338 with prostate cancer) and with modest heterogeneity (Isquared, 66%) were selected. The %p2PSA pooled estimates were always greater than those of PSA, and so was the cumulative pooled AUC (0.687 versus 0.538; p<0.001). The diagnostic odds ratio was more than double for %p2PSA than for total PSA (4.0 versus 1.7). With a sensitivity of 0.95, routine p2PSA testing may result in up to 10% fewer unnecessary biopsies than the use of PSA for screening. The AUC of phi was slightly but not significantly better than that of %p2PSA (0.736 versus 0.717; p=0.21). Conclusions: These findings provide a rationale for planning further studies to assess whether %p2PSA testing may generate more favourable outcomes in terms of mortality and quality of life. Direct comparison does not permit the conclusion that the phi is globally superior to %p2PSA for detecting prostate cancer. © 2012 Springer-Verlag Italia Riassunto.


Lippi G.,U.O. Diagnostica Ematochimica | Mattiuzzi C.,Servizio Governance Clinica | Banfi G.,University of Milan | Buttarello M.,Laboratorio Analisi | And 11 more authors.
Biochimica Clinica | Year: 2013

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


Mattiuzzi C.,Servizio Governance Clinica | Cervellin G.,Unita Operativa di Pronto Soccorso e Medicina dUrgenza
Clinical Biochemistry | Year: 2013

An early diagnosis is crucial for effective triage and management of patients with suspected acute myocardial infarction (AMI). Although troponin testing is the cornerstone of diagnosis, the sensitivity of this biomarker is still suboptimal at patient admission. The heart-type fatty acid binding protein (H-FABP) is an early and sensitive biomarker of myocardial ischemia, whose appropriate setting is in combination with troponin testing. We performed a systematic review and meta-analysis of articles that have assessed the combination of troponin and H-FABP in the early diagnosis of AMI. Eight studies, totaling 2735 patients, met the inclusion criteria but none of them used a high-sensitivity troponin immunoassay. The between-study variation was high (98.5%), and attributable to heterogeneity. When considered alone, troponin exhibited a significantly greater pooled area under the curve (AUC) than H-FABP alone (0.820 versus 0.784; p < 0.001). The pooled specificity was also higher for troponin alone than for H-FABP alone (0.94 versus 0.83; p < 0.001), whereas the cumulative sensitivity was lower for troponin than for H-FABP (0.73 versus 0.80; p. =0.02). The combination of both biomarkers exhibited a greater AUC than troponin alone (0.881; p < 0.001), as well as a higher pooled sensitivity (0.91; p < 0.001), which was however counterbalanced by a lower specificity (0.82; p < 0.001). These results attest that the combination of H-FABP with a conventional troponin immunoassay seems advantageous for increasing the sensitivity of the former biomarker, at the expense of a lower specificity. The introduction of H-FABP testing would hence require careful assessment of laboratory data or clinical signs and symptoms for excluding sources of elevation different from AMI. Further studies are needed to assess the diagnostic effectiveness of combining H-FABP with a high-sensitivity troponin immunoassay. © 2012 The Canadian Society of Clinical Chemists.


Mattiuzzi C.,Servizio Governance Clinica | Banfi G.,Instituto Ortopedico IRCCS Galeazzi
Bioanalysis | Year: 2013

The use of illicit substances and methods contravenes the ethics of sports and may be associated with side effects. Antidoping testing is an essential tool for preventing or limiting the consequences of cheating in sports. As for conventional laboratory testing, major emphasis has been placed on analytical quality, overlooking the inherent risks that may arise from analysis of unsuitable doping samples. The adherence to scrupulous criteria for collection, handling, transportation and storage of samples, especially blood and urine samples, is essential. The leading preanalytical variables that influence doping sample quality include biological variability, sample collection, venous stasis, spurious hemolysis and presence of other interfering substances, sample manipulation and degradation, and inappropriate conditions for transportation and storage. This article provides a personal overview about the current challenges in preanalytical management of doping samples, as well as potential solutions for preventing the negative impact of preanalytical variables on sample quality and test results. © 2013 Future Science Ltd.


Cervellin G.,Unita Operativa Pronto Soccorso e Medicina dUrgenza | Mattiuzzi C.,Servizio Governance Clinica
Biochemia Medica | Year: 2013

Background: A number of preanalytical activities strongly infl uence sample quality, especially those related to sample collection. Since blood drawing through intravenous catheters is reported as a potential source of erythrocyte injury, we performed a critical review and meta-analysis about the risk of catheter-related hemolysis. Materials and methods: We performed a systematic search on PubMed, Web of Science and Scopus to estimate the risk of spurious hemolysis in blood samples collected from intravenous catheters. A meta-analysis with calculation of Odds ratio (OR) and Relative risk (RR) along with 95% Confi dence interval (95% CI) was carried out using random effect mode. Results: Fifteen articles including 17 studies were fi nally selected. The total number of patients was 14,796 in 13 studies assessing catheter and evacuated tubes versus straight needle and evacuated tubes, and 1251 in 4 studies assessing catheter and evacuated tubes versus catheter and manual aspiration. A signifi cant risk of hemolysis was found in studies assessing catheter and evacuated tubes versus straight needle and evacuated tubes (random effect OR 3.4; 95% CI = 2.9-3.9 and random effect RR 1.07; 95% CI = 1.06-1.08), as well as in studies assessing catheter and evacuated tubes versus catheter and manual aspiration of blood (OR 3.7; 95% CI = 2.7-5.1 and RR 1.32; 95% CI = 1.24-1.40). Conclusions: Sample collection through intravenous catheters is associated with signifi cant higher risk of spurious hemolysis as compared with standard blood drawn by straight needle, and this risk is further amplifi ed when intravenous catheter are associated with primary evacuated blood tubes as compared with manual aspiration.


Mattiuzzi C.,Servizio Governance Clinica | Comelli I.,Unita Operativa Pronto Soccorso e Medicina dUrgenza | Cervellin G.,Unita Operativa Pronto Soccorso e Medicina dUrgenza
Blood Coagulation and Fibrinolysis | Year: 2013

It is now widely acknowledged that larger platelets are biologically more active and express a greater prothrombotic potential, but there is no definitive evidence on the diagnostic accuracy role of mean platelet volume (MPV) in patients with ischemic heart disease. We performed an electronic search for articles that have assessed the diagnostic accuracy of MPV in patients admitted at the emergency department with a suspected diagnosis of ischemic heart disease, including articles in which the exact number of true-positive, false-positive, false-negative and true-negative test results could be either directly or indirectly extracted. Heterogeneity was assessed by I test. The cumulative estimates and 95% confidence interval (95% CI) of sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), area under the receiver operator characteristic (ROC) curve (AUC) and diagnostic odds ratio (DOR) were calculated using a random effect model. Three studies were finally included in our analysis (mean quality score, 10.8) totaling 3577 participants (566 cases and 3011 controls). The between-study variation was high (I, 96.2%; P<0.001). The pooled estimates were 0.820 (95% CI 0.786-0.851) for sensitivity, 0.461 (95% CI 0.443-0.479) for specificity, 0.932 (95% CI 0.918-0.944) for NPV and 0.222 (95% CI 0.205-0.241) for PPV and 0.652 (95% CI 0.596-0.707) for AUC. The DOR was 3.9 (95% CI 2.3-6.5), with 0.52 diagnostic accuracy. The outcome of this meta-analysis suggests that MPV does not meet the requirements for efficient triage of patients in emergency department when used as stand-alone test, whereas its combination with high-sensitive troponin immunoassays merits further investigations. © 2013 Wolters Kluwer Health Lippincott Williams & Wilkins.


Lippi G.,UO Diagnostica Ematochimica | Mattiuzzi C.,Servizio Governance Clinica | Banfi G.,University of Milan | Buttarello M.,Laboratorio Analisi | And 11 more authors.
Rivista Italiana della Medicina di Laboratorio | Year: 2013

Summary: The collection of venous blood is essential to obtain biological samples for performance of laboratory testing. Although there is widespread perception that this practice is simple and free of complications and side effects, it is undeniable that the vast majority of laboratory errors arises from ignorance, incompetence or negligence during venipuncture. It has hence become advisable to edit a document in simplified form of checklist, consisting of a concise but comprehensive list of activities to complete or verify, in order to prevent the onset of errors during venous blood collection. In the intention of authors and of the Italian societies of laboratory medicine, this synthetic checklist is a modular tool, adaptable to different local contexts, it can be easily and gradually implemented, is supported by scientific evidence and consensus of experts, has been created with the support of different healthcare professionals, is adherent to the best practices and requires minimal resources for implementation. It is reasonable to assume that this checklist may be able to withstand system and individual changes, strengthening the standards for safety of both operators and patients, limiting potential failure patterns. We also hope that the checklist may be implemented in all healthcare facilities where routine venous blood collection is performed, after adaptation to suit characteristics of local organization. © 2013 Springer-Verlag Italia. Parole chiave: Emolisi ChecklistCampioni non idoneiVariabilità preanalitica Prelievo venoso Raccomandazioni.


Lippi G.,UO Diagnostica Ematochimica | Mattiuzzi C.,Servizio Governance Clinica
Recenti Progressi in Medicina | Year: 2014

Cardiovascular disease is a leading cause of mortality around the globe. The atherosclerotic disease is a systemic chronic condition that begins in early childhood and progresses throughout adulthood. Since atherosclerosis is a preventable condition and is largely caused by accumulation of cholesterol in the arteries, the treatment of hypercholesterolemia is one of the mainstay in primary and secondary prevention. According to the new guidelines of the American College of Cardiology and American Heart Association (ACC/AHA), which substantially revise those previously published by the National Cholesterol Education Program (NCEP), statin treatment should be extended to all individuals with low density lipoprotein (LDL) cholesterol ≥70 mg/dL (1.81 mmol/L), presence of diabetes or cardiovascular risk ≥10 years 7.5%, thus generating a number of important clinical (i.e., increased number of subjects at risk of statin-related myopathy) and economic (incremental cost of the drugs) consequences, that will be discussed in this article.

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