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Objective: To evaluate the role of brain natriuretic peptide (BNP) in predicting the progression of heart failure (HF) after cardiac resynchronization therapy (CRT). Background: It has been shown that BNP predicts the prognosis and can guide the treatment of HF. Methods: We studied 50 consecutive patients (61±10 years, 23 male) with HF (8 with ischaemic cardiomyopathy), NYHA class III, left bundle branch block, left ventricular ejection fraction (LVEF) ≤35% (mean 24±6%) who underwent CRT. All patients were taking conventional HF therapy and were clinically stable. Plasma BNP levels were evaluated by two-site dual-monoclonal immunochemiluminescent assay before, and 1 month after CRT. The predictive value of BNP was assessed using univariate and multivariate regression analyses. Results: During follow-up (mean 19±12 months), HF progression was observed in 14 patients (11 were hospitalised and 3 died after worsening of HF). Multivariate analysis showed that BNP levels before (HR: 2.07; CI: 1.19–3.62; p=0.01) and 1 month after CRT (HR: 2.23; CI: 1.26–3.94; p=0.006) were significantly related to events. At 1 month, a BNP level >91.5 pg/ml had 89% sensitivity, 59% specificity, and negative and positive predictive values of 96% and 33%, respectively, for HF progression after 12 months. Conclusions: HF patients with high BNP values after 1 month of CRT have worse prognosis during follow-up. Therefore, in these patients other therapeutic options should be considered.

Background Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting the joints. A number of novel treatment modalities have been introduced over the past years, and rheumatologists are now attempting to institute optimal treatment in recent-onset arthritis. To facilitate diagnosis during the early stages of disease, when often not all clinical symptoms are manifest, a good serological marker is needed. Methods Antibodies directed to citrullinated proteins provide this ability. The most sensitive assay for detecting these antibodies is the so-called anti-cyclic citrullinated peptide, second generation (CCP II) enzyme-linked immunosorbent assay (ELISA). Results The diagnostic and prognostic potential of anti-CCP antibodies and the availability of a fully automated assay method lead us to conclude that the test is satisfactory for routine use as a serological marker of RA. In addition, we consider the potential of multiplex autoantibody assays, including miniaturized, high-throughput microarray technology, to improve diagnosis and prognostication in early onset arthritis patients.

Background Autoantibodies against cyclic citrullinated peptide (anti-CCP) are considered to be a sensitive and specific marker for rheumatoid arthritis (RA). This study evaluated the analytical performance and clinical correlation of an automated enzyme immunoassay (DSX, DINEX Technologies), for the detection of anti-CCP autoantibodies (DIASTAT™ anti-CCP, Axis-Shield, DUNDEE UK). Methods Commercial controls and serum pools were used to determine its precision, analytical sensitivity, functional sensitivity and linearity. Sera from 83 patients with established RA and from 140 controls, including patients with various autoimmune diseases, viral infections and cancer, as well as sex- and age-matched healthy subjects, were studied. The rheumatoid factor (RF) was also assayed in each sample, and the results were compared to the anti-CCP findings. Results The total imprecision (CV%) was 4.7–7.2% for concentrations ranging between 1.98 and 71.81 U/mL. The lower detection limit was 0.038 U/mL. At a cut-off of 5 U/mL, the sensitivity and specificity for RA were 67.5% and 99.3%, respectively. The RF had a sensitivity of 66.3% and a lower specificity 82.1% than anti-CCP. When the two antibodies were used together, the specificity was 99.1%. Conclusions The anti-CCP assay we examined on a fully automated system showed a good analytical performance (analytical and functional sensitivity, linearity) and good clinical correlation. We conclude that this system can provide rapid, useful data.

Anthracyclines are used extensively in the therapy of hematologic malignancies. However, their use has been limited by acute and chronic cardiotoxicity. Cardiac troponins have emerged as sensitive and specific markers of even minor myocardial damage. In this study we prospectively evaluated serial measurements of serum cardiac markers and echocardiography in patients with de novo acute myeloid and lymphoid leukemias (AML and ALL, respectively) treated with anthracyclines. We examined and subdivided 79 patients into 3 groups: group 1 (37 patients with AML, all60 years), group 2 (25 with AML, all 260 years), group 3 (17 with ALL). Serum specimens were collected before treatment and during and after therapy and were analyzed for troponin I (Tnl), myoglobin, creatine phosphokinase-muscle myocardium isoenzyme B, and lactate dehydrogenase concentrations. In group 1, 4 of the 37 patients (11%) had increased levels of Tnl on the 14th day of induction therapy, but by the 28th day the Tnl level had returned to normal in 3 of these 4 patients. In group 2, 3 of the 25 patients (12%) demonstrated increased Tnl concentrations on the 7th day of induction therapy, but by the 14th day these levels had normalized in 2 of the 3. In group 3, we detected no increased Tnl concentrations. Echographic study did show a significant correlation with the Tnl levels (P.001), involving a reversible decrease in left ventricular ejection fraction among patients with increased Tnl levels (0.15 ng/mL) on day 14 in group 1 and on day 7 in group 2. These results may aid the clinician in the treatment of patients by identifying high-risk patients who may benefit from closer observation or supportive cardiac therapy.

Background: Acute coronary syndrome is a major cause of death, morbidity and access in emergency departments (ED). Methods: We evaluated a point-of-care testing (POCT) for the determinations of cardiac markers in an emergency department (ED), defining the clinical efficiency (management of patient with chest pain) and economic effectiveness (rationalization of preanalytical phase) related to data of Core Lab. Results: The results of analytical performances showed a good correlation (cTnI r2=0.89, myoglobin r2=0.84, CK-MB r2=0.9) between POCT and Core Lab and a significant decrease of the turn around time (TAT): difference of medians=−54 min, 95% CI from −48 to −60 min. Conclusions: Our data confirmed that the accurate utilization of POCT in the ED assumes an effective triage of patient with chest pain and the improvement of preanalytical phase out of the laboratory (delivery of specimens) and within the laboratory reception, centrifugation. However, efficiency must be linked to methodological and quality control of the Core Lab, mainly through connectivity.

Background: The heavy burden of the costs of medical care has brought changes in the public health policy. The changes are partly related to the health management factors, but several cultural, social and environmental factors have also had a significant impact on healthcare. The role of the laboratory is now considered amidst changes that have occurred in the American health model (free-trader) and in the European–Canadian model (universalistic). Moreover, costs and clinical decision-making in laboratories in Italy have also changed in response to the new focus on the pre- and post-analytical phases of the testing process. Methods: In the present study, we used the Laboratory Information System (LIS) to evaluate whether the time involved in stages in the turnaround time (TAT) (admission, performance of tests, validation and decision-making for treatment) were reduced following improvements made to the laboratory organization and management of the pre-analytical and post-analytical phases. In particular, an analysis was made of laboratory testing for myocardial markers in patients with acute coronary syndrome. Results: TAT for myocardial markers in an emergency setting was reduced by 30% following changes made in the laboratory organization and in the management of the pre-analytical and post-analytical phases of the testing process. Conclusions: Thanks to changes in healthcare service/system in Italy, laboratory services will now play a crucial role in cultural and socioeconomic changes, particularly where testing processes and techniques are concerned.

Objectives: To determine the diagnostic accuracy of hysteroscopy in the diagnosis of endometrial hyperplasia in women with abnormal uterine bleeding. Methods: From 1993 through 1995, 980 women referred to our institution for abnormal uterine bleeding underwent diagnostic hysteroscopy with eye direct biopsy of the endometrium in case of macroscopic abnormalities. Hysteroscopic features were compared with pathologic findings in order to detect the reliability of the endoscopic procedure. Statistical analysis was performed with the McNemar test. Results: Positive predictive value of hysteroscopy in the diagnosis of endometrial hyperplasia accounted for 63%. In fact hysteroscopic diagnosis of endometrial hyperplasia was confirmed at pathologic examination in 81 out of 128 patients. Sensitivity and specificity of the endoscopic procedure accounted for 98% and 95%, respectively. Negative predictive value accounted for 99%, as only two cases of atypical hyperplasia were missed at hysteroscopy. Positive predictive value was higher in postmenopausal patients compared to women in the fertile age (72 vs. 58%). Conclusions: Overall, results appear encouraging, since no case of endometrial hyperplasia was missed by hysteroscopy. The high diagnostic accuracy, associated with a minimal trauma, renders hysteroscopy the ideal procedure for both diagnosis and follow-up of conservative management of endometrial hyperplasia.

Guidelines aim to assist physicians about appropriate health care for specific clinical circumstances. Therefore, they must be continuously updated, integrated and tailored to local situations.We applied recently developed guidelines for autoantibody testing by assessing their economic (efficiency) and clinical (effectiveness) impact. Since June 2002, a test order algorithm has been adopted for autoantibody testing requests (3258). In particular, the guidelines were modified taking into account the needs of different departments and the results were compared to those (2762) of the previous period (January-May 2002) that had not been integrated with any diagnostic algorithm.A significant reduction in the number of anti-double stranded DNA (anti-dsDNA) (21.4%) and anti-Extractable Nuclear Antigens (anti-ENA) (19%) was found (p0.0001), while the number of anti-nuclear antibody (ANA) test was unchanged (p=n.s.); further reduction in clinically inappropriate test request rates (23%) was observed.The application of guidelines allowed the improvement of diagnostic tests' efficiency and clinical effectiveness (patient's outcomes), thus confirming the need to apply eventual modifications to the diagnostic process taking into consideration different clinical needs.

Study Objective To evaluate the quantity of biopsy tissue obtained by hysteroscopic grasp technique compared with classic punch technique. Design Observational study (Canadian Task Force classification II-2). Setting University hospital. Patients One thousand two hundred seventy-six women. Interventions Targeted biopsies performed in an office setting using two biopsy forceps, classic spoon and crocodile, and two methods, classic punch and grasp technique. Measurements and Main Results With either biopsy forceps, the mean increase in amount of tissue obtained by grasp technique compared with punch technique was statistically significant (p Conclusion Targeted biopsy, when performed with the appropriate instrument and applying correct technique, can provide the pathologist with a large amount of tissue (mean 5.7 mm2) that is invariably adequate for histologic examination.

The aim of this study was to identify patients with myocardial necrosis in pre-hospital phase during transport by ambulance, without ST-segment elevation (NSTE) on the ambulance ECG. The analytical performance of the i-STAT troponin I (cTnI) method was assessed. A total of 53 NSTE ambulance ECG patients admitted to hospital were followed. The ambulance had experimental software able to receive data from the i-STAT device and transmit it to a protected address and server. cTnI mean values from 2.0 to 34 microg/L showed a total CV of 3.0-5.6%. The detection limit was 0.016 microg/L. A mean cTnI concentration of 0.09 microg/L was associated with a CV of 8.0% (decision limit). The i-STAT cTnI method was linear for concentrations from 0 to 35 microg/L. There was no effect (p0.05) of interfering substances. For point-of-care testing (POCT), cTnI was0.09 microg/L in 20 AMI patients (91%). The median ambulance turnaround time (TAT) was 12 min and median hospital TAT was 40 min, a difference of 28 min. The high sensitivity of the i-STAT cTnI method integrated with tele-medicine procedures could play an important role in the management of acute coronary syndrome patients related to the pre-hospital phase (early diagnosis and treatment in the ambulance). These approaches may allow improvements in patient outcomes and continuous monitoring of the POCT network in the central laboratory, thus meeting quality requirements.

Clinical laboratories have undergone major changes due to technological progress and economic pressure. While costs of laboratory testing continue to be the dominant issue within the healthcare service worldwide, quality, effectiveness and impact on outcomes are also emerging as critical value-added features. Five Italian laboratories are therefore promoting a network of excellence by investigating markers of effectiveness of laboratory services and sharing their experience of using them in clinical practice. In the present study we report preliminary data on indicators of quality in all phases of the so-called total testing process, the key to evaluating all phases of the total testing process, including the appropriateness of test requests and data interpretation. Initial findings in evaluating pre-analytical causes of specimen rejection in three different laboratories and the effects of introducing three laboratory clinical guidelines are reported. These data should stimulate debate in the scientific community and encourage more clinical laboratories to use the same indicators to improve clinical effectiveness and clinical outcomes within the healthcare service.

Background Cardiac multimarker strategy is recommended by the IFCC, ESC and the ACC for an early risk stratification in non-ST-segment elevation (NSTE) ECG patients with chest pain. A new approach, based on protein biochip array technology, performs simultaneously: cTnI, CK-MB, myoglobin, CAIII, GFBB and FABP using a single chip. Methods We evaluated the analytical performance of the Randox-Evidence Investigator™-biochip cardiac panel according to IFCC recommendations and NCCLS guidelines; a preliminary clinical evaluation was carried out on chest pain NSTE ECG patients, to evaluate the accuracy of the multimarker approach in an early diagnosis of AMI, related to the final diagnosis (ACC/ESC criteria). Results Troponin, CK-MB and FABP methods provide reproducible within-run and between-day results (total %CVs from 5.9% to 9.7%), and myoglobin and CAIII methods showed the total %CVs from 16.4% to 25.8%. Our preliminary clinical data suggests that FABP had a better diagnostic performance (sensibility = 100%) than myoglobin (sensibility = 75%) to detect AMI in the first hours after the onset of the chest pain and myoglobin/CAIII ratio (specificity = 92.9%) improved the myoglobin specificity. Conclusions Cardiac markers have different diagnostic roles and, in this contest, biochip technology could be an interesting approach supporting clinical expectations.

Methods to quantify B-type natriuretic peptide (BNP) and N-terminal-propeptide (NT-proBNP) in plasma or serum samples are well established. We assessed the analytical performance of the Dimension RxL NT-proBNP method (Dade-Behring). Evaluation of different sample types was carried out. Controls and heparin plasma pools were used to determine the detection limit, precision, and linearity. Sample stability and the effect of interfering substances on the NT-proBNP concentrations were evaluated. Agreement between Dimension RxL and Elecsys 2010 (Roche Diagnostics) NT-proBNP methods was assessed. The influence of age and sex on NT-proBNP concentrations was evaluated in healthy subjects. Heparin plasma should be the matrix of choice. The detection limit was 2.0ng/L. The total imprecision was 2.6–3.6% for concentrations from 231 to 9471ng/L; mean NT-proBNP concentrations of 21 and 15ng/L were associated with coefficients of variation of 9.9% and 14.7%, respectively. The method was linear up to 32,650ng/L. There was no effect of temperature, freeze-thaw cycles and interfering substances. A bias was detected when Dimension RxL and Elecsys 2010 NT-proBNP methods were compared. Age and sex were significantly and independently related to NT-proBNP concentrations. The Dimension RxL NT-proBNP method, like the Elecsys 2010, is suitable for routine use in the diagnosis of heart failure.

To achieve rapid assessment of chest pain in emergency/cardiology departments, a short turnaround time for cardiac marker testing is necessary. Nevertheless, Total Quality Management principles must be incorporated into the management of point-of-care testing (POCT); in this setting we implemented the Stratus CS assay as POCT for cardiac markers in our emergency/cardiology department. The analytical performance of the troponin I method was evaluated; information connectivity between the Stratus CS data management system and the laboratory information system was implemented and practical training of testing personnel was carried out at the POCT site. A total of 41 non-ST-segment elevation patients admitted to the hospital were followed to evaluate the appropriateness of hospital admission, formulated on the basis of the cardiac troponin-I level measured at the POCT site by clinical staff. Our preliminary clinical data suggest that the high sensitivity of the Stratus CS troponin method could play an important role in the early identification of patients with acute myocardial infarction in a low to intermediate-risk population for acute coronary syndrome. Our POCT model suggests that the central laboratory could ensure that the POCT program remains in compliance with quality requirements. Nevertheless, our comparison studies suggest that the implementation of POCT requires a high level of integration between cardiologists and pathologists to guarantee appropriate interpretation of the monitoring results for suspected ACS patients.

Background : The need to reduce costs in Laboratory Medicine is often related to the possibility of reducing test requests without taking into account patients' outcomes. Therefore, the term “appropriateness” in Laboratory Medicine as referred to the specific steps (pre-analytical, analytical, post-analytical) and related to the clinical process could allow the improvement of clinical effectiveness and economic efficiency. Methods : Our experience has shown an improvement in analytical appropriateness (reorganization and re-engineering by Laboratory automation) and pre-analytical appropriateness (critical revision of the panel for cardiac markers) by evaluating the workload and errors rate in the pre-analytical phase. Results : We obtained an economic saving (119,580 euro/year) in cardiac markers request (analytical appropriateness: 60%, pre-analytical appropriateness: 40%) and also an improvement in clinical appropriateness (diagnosis and therapy). Conclusions : Our data confirm the need to improve communications between physicians and Laboratory Medicine as regards the pre-analytical step and to implement educational programs for defining criteria and procedures. Appropriateness in analytical and post-analytical steps contribute to achieve economic saving (Core lab, POCT) and improvement of the turn-around time (TAT).

Cardiac troponin I (cTnI) is a sensitive and specific biochemical marker of myocardial damage. We assessed the analytical performance of the Vidas Troponin I assay (Biomerieux). Controls and serum pools were used to determine the precision, analytical sensitivity and linearity; 97.5 and 99.5 percentiles concentrations were determined from the reference population. Fifty corresponding samples of serum and plasma (lithium-heparin) were tested and the results compared. The in vitro stability of serum and plasma samples was assessed at 20 degrees C, 4 degrees C and -20 degrees C, respectively. Samples of serum were used to assess the agreement between the Vidas Troponin I method and the revised Dimension RxL cTnI method (Dade-Behring). The total imprecision (CVs) was 13.1-5.2% for concentrations ranging between 0.25 and 19.8 microg/l cTnI. The lower detection limit was0.1 microg/l. The upper reference limit (97.5 and 99.5 percentiles) was 0.11 microg/l and 0.12 microg/l, respectively (CV10%). The assay was linear up to 21 microg/l. The concentrations in lithium-heparin plasma were higher compared to those of the matched serum samples. The study of the agreement between the Vidas and Dimension RxL cTnI assays showed a total concordance of 96% with a bias value of -0.042. The Vidas Troponin I test is a fast, precise and sensitive method for the determination of cTnI.

Objective: To assess the diagnostic accuracy of office hysteroscopy by comparing the hysteroscopic findings with the histologic findings on the hysterectomy specimens. Design: Retrospective clinical study. Setting: University-affiliated hospital. Patient(s): Review of the hospital records of 443 patients who underwent office hysteroscopy and, within 2 months, hysterectomy. Intervention(s): We compared the hysteroscopic findings (including targeted biopsies) with the histologic findings that were obtained after hysterectomy. The results of this study were then compared with those of a previous study in which we examined the diagnostic accuracy of dilatation and curettage (D&C). Main Outcome Measure(s): We evaluated the diagnostic accuracy of office hysteroscopy. Result(s): When compared with the histologic diagnosis of the uterus, the hysteroscopic findings showed a diagnostic sensitivity of 98%, a specificity of 95%, a positive predictive value (PPV) of 96%, and a negative predictive value (NPV) of 98%. Hysteroscopy was found to have a greater diagnostic accuracy than D&C: the sensitivity and the NPV of the two diagnostic procedures were statistically different. Conclusion(s): Office hysteroscopy is confirmed as a powerful diagnostic tool, but targeted biopsies, performed with a small diameter operative hysteroscope, must be performed in cases of suspect endometrium to confirm the image-based diagnosis.

To evaluate the efficiency of paracervical anesthesia in reducing pain and the incidence of vasovagal reactions during diagnostic hysteroscopy with endometrial biopsy in postmenopausal women.A randomized, placebo-controlled, double-blind study. Seventy-two postmenopausal women underwent diagnostic hysteroscopy and endometrial biopsy. Hysteroscopies were performed by using a lens-based endoscope with a diameter of4 mm and endometrial biopsies by using a 3-mm Novak's curette. Ten milliliters of 1.5 mepivacaine or saline solution was injected at the junction of the cervix and vagina (at the 4 and 8 o'clock positions) by means of an appropriate needle before performing the intrauterine procedures. Referred pain was evaluated by means of a visual analogue scale; continuous monitoring of heart rate and blood pressure was also performed.Paracervical anesthesia significantly reduced pain at hysteroscopy and biopsy. The incidence of vasovagal reactions was also significantly lower in the anesthetized group.Paracervical anesthesia is effective for hysteroscopy and endometrial biopsy in postmenopausal women and may be indicated particularly for patients with cervical stenosis, for very anxious subjects and in all situations where pain stimulation could trigger threatening side effects due to systemic pathologies.

Joint involvement in systemic sclerosis (SSc) commonly occurs as arthralgias, while a true arthritis is less frequent. The most common arthritis developing in SSc is rheumatoid arthritis (RA) and its diagnosis may be misled by concomitant joint contracture or tendon sheath involvement due to SSc. Anti-citrullinated cyclic peptide (CCP) antibodies are an emerging tool to diagnose RA and have shown to be more specific than rheumatoid factor. We assessed the prevalence of anti-CCP antibodies in SSc patients and evaluated their sensitivity and specificity for associated RA. Searching for RF and anti-CCP antibodies and joint examination were carried out in sixty consecutive SSc patients. Hands and feet standard x-rays were performed in patients complaining with arthralgia and/or arthritis. Six out of sixty (10%) SSc patients had RA according to 1987 ARA revised criteria. Anti-CCP were detected in 5 patients (sensitivity 83%) and RF was present in all RA patients (sensitivity 100%). However, anti-CCP antibodies had a much higher specificity (94%) than RF (41%) for RA. Our study suggests that anti-CCP antibodies are a useful test to identify patients with SSc having also RA. This is crucial in the management of SSc because may allow an adequate therapy of RA and prevent further joint damage in patients who already have a poor quality of life.

Twenty adult patients with relapsed or refractory acute lymphoblastic leukemias (ALL) received a regimen employing two courses of mitoxantrone 12 mg/m2 by rapid intravenous infusion on days 1, 2 and 3 and cytosine arabinoside (ARA-C) 200 mg/m2/day by continuous infusion on days 1-7. Complete remission (CR) was achieved in 10 of 20 (50%) patients (3 refractory and 7 relapsed). Median duration of CR was 5 months (range 2-9). The treatment was associated with minimal extrahematologic toxicity, with no cardiac toxicity. Our results are nearly in line with therapeutic responses obtained with regimens employing megadose therapy (HD ARA-C). Because of acceptable toxicity, mitoxantrone plus continuous infusion of a standard dose of ARA-C could be considered for relapsed of refractory ALL patients eligible for an intensive therapeutic approach (bone marrow transplantation) after a second CR.