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We seek correlation consistent double- and triple-zeta basis sets that perform optimally for extrapolating the correlation energy to the one-electron complete basis set limit. Since the methods used are approximate, the novel basis sets become method specific in the sense of performing best for the chosen level of theory. Such basis sets are also shown to perform accurately for tensorial properties and do not significantly alter the Hartree-Fock energy. Quantitatively, the extrapolated correlation energies from (oVdZ, oVtZ) outperform typically by three- to fivefold those obtained from traditional ansatzes with similar flexibility, thus being (VtZ, VqZ) type or even better. They may even outperform explicitly correlated ones. Not surprisingly, the outperformance in relative energies (e.g., atomization and dissociation energies, and ionization potential) is somewhat downscaled, albeit consistently better than with traditional basis sets. As a case study, we also consider the polarizability of p-nitroaniline, a sizeable system for which complete basis set (CBS)(oVdZ, oVtZ) calculations are shown to outperform equally expensive CBS(VdZ, VtZ) results.

A methodology previously suggested for niobium clusters is here applied to the prediction of the ground spin-state of the niobium clusters doped with aluminum atoms. By using all-electron density functional theory with Douglas-Kroll-Hess correction, the spin-state, geometry, hardness, binding energy, ionization potential, electron affinity, and mean static dipole polarizability of the Nb x Al y clusters are examined. The ground spin-states obtained from the energy minimization were confronted with the results provided by the maximum hardness principle (MHP) and by the minimum polarizability principle (MPP). In general, the MHP and MPP have yielded the expected results, i.e., in agreement with the ones obtained from the minimum energy. Additionally, were compared the theoretical results for polarizability, ionization potential, and reactivity with the available experimental values.

A detailed analysis of the electronic structure of the ground and first excited spin state of three diatomic molecules ( N2, BH and CO) under static applied electric field is performed at CCSD(T), DFT, MRCI and MRCI(Q) levels of theory. Our findings have revealed that by boosting the applied field one induces changes in the occupation numbers of molecular orbitals, giving rise to changes in the equilibrium geometry and in the HOMO-LUMO energy gap. Specifically, singlet to triplet spin transition can be induced by increasing the applied electric field beyond a critical value. Accordingly, affecting the accuracy of the widely used expression of energy expanded in Taylor series with respect to the applied electric field. © 2018 Wiley Periodicals, Inc.

The performance of various hierarchized basis sets has been assessed by extrapolating the correlation energy to the estimated one-electron complete basis set limit. New hierarchical numbers are obtained which are found to lie close to previously reported ones for the Dunning correlation-consistent basis. Universal hierarchical numbers are also suggested, with correlation extrapolations showing a significantly better performance than when based on traditional protocols. It is observed that the accuracy of the extrapolation is enhanced when the underlying plot approaches linearity.

A simple scheme is suggested to extrapolate the valence electron correlation to the one-electron complete-basis-set limit in species formed by atoms of hydrogen through neon. The performance of the novel scheme is benchmarked for the correlation energy with a data set of 106 systems and, for the polarizability, with 8 molecules. For the former, the results are excellent, most often better than when extrapolated with the best available two-parameter protocols. For the polarizability, they show an enhancement relative to the raw ab initio values, and good agreement with the experimental ones.

Supporting InformationABSTRACT: A method previously suggested to calculate the correlation energyat the complete one-electron basis set limit by reassigning the basis hierarchicalnumbers and using the unified singlet- and triplet-pair extrapolation scheme is hereutilized to extrapolate tensorial properties, with specific use for the polarizabilitiesof eight molecules whose raw values are obtained with second-order Moller−Plesset perturbation theory and coupled-cluster singles and doubles excitationmethods, both without and with inclusion of the perturbative triples correction.Good agreement is obtained with the best available estimates even when the (d, t)pair of hierarchical numbers is utilized to perform the extrapolations. Thisconceivably reinforces our previous finding that there is no good reason to excludedouble-ζ results in extrapolations, especially if the basis is calibrated to complywith the theoretical model.

In this paper, an augmented all-electron double-ζ basis set is used in calculations of the structure and electronic properties of small niobium clusters. The B3PW91 and M06 DFT functionals with and without second order Douglas–Kroll–Hess (DKH) scalar relativistic corrections are also utilized. Furthermore, an additional d Gaussian type function is introduced in the standard basis sets in order to improve the description of the clusters orbitals in the valence band. Our findings show that the extra d function is important to yield accurate results of electronic properties and, in addition, the DKH corrections can be relevant when the all-electron basis sets are used in the calculations. Our best results are obtained with the M06 functional together with the DKH second order corrections and with the extra d function added to the all-electron basis set.

It is shown that Hartree–Fock calculations using basis sets of the correlation consistent family and arbitrary hierarchical numbers can be extrapolated to the complete basis set limit with an accuracy higher or at least similar than achieved thus far with the best available schemes. The same protocol is valid for multireference self-consistent-field energies including only the nondynamical correlation. Test sets containing neutral and ionic species as well as closed-shell and open-shell systems are used for numerical illustration.

By using density functional theory, spin states, geometries, and mean static dipole polarizabilities of group VIIIA metallocenes M(C5H5)2 (M = Fe, Co, Ni, Ru, Rh, Pd, Os, Ir, and Pt) are examined. For all metallocenes studied, comparison of the polarizability of the accessible spin states reveals that the lowest polarizability was found for the spin ground state. Therefore, our findings indicate that the minimum polarizability principle might be useful in determining the ground state multiplicity for transition metal metallocenes. The metallocenes from the group 8 and group 9 possess the same multiplicity, singlet and doublet, respectively. Additionally, one observes that the polarizability increases monotonically with the atomic number of the central metal atom for metallocenes from the same column. The B3LYP/ADZP is one of the most reliable procedure tested so far to predict the static dipole polarizability of the complexes studied here, with mean absolute deviation from the experimental data smaller than 1.8 au.

Segmented all-electron contracted sextuple zeta valence plus polarization function (6ZP) basis sets for the elements from H to Ar were constructed to be used in conjunction with the non-relativistic and Douglas–Kroll–Hess Hamiltonians. The scalar relativistic effect at the coupled cluster level of theory on atomization energy for a sample of molecules was discussed. Additional improvements in the atomization energies were achieved by applying corrections due to core/valence correlation, atomic spin–orbit effects, and addition of tight d and f functions on second-row elements. This leads to estimates for the heat of formation of gaseous boron and carbon tetrafluoride.

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.

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.

A method previously suggested to calculate the correlation energy at the complete one-electron basis set limit by reassignment of the basis hierarchical numbers and use of the unified singlet- and triplet-pair extrapolation scheme is applied to a test set of 106 systems, some with up to 48 electrons. The approach is utilized to obtain extrapolated correlation energies from raw values calculated with second-order Moller-Plesset perturbation theory and the coupled-cluster singles and doubles excitations method, some of the latter also with the perturbative triples corrections. The calculated correlation energies have also been used to predict atomization energies within an additive scheme. Good agreement is obtained with the best available estimates even when the (d, t) pair of hierarchical numbers is utilized to perform the extrapolations. This conceivably justifies that there is no strong reason to exclude double-zeta energies in extrapolations, especially if the basis is calibrated to comply with the theoretical model.

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.

Contact hysteroscopy has been replaced by a new technique based on the use of a special hysteroscope. The instrument was designed to study the squamocolumnar junction and the lesions of the portio. A new technique, endometrial dating, uses the Hamou hysteroscope to study endometrial physiology. We improved endometrial dating and discovered a new pattern, the pseudofunctional dysvascular endometrium (PFDE), that seemed to pertain to uterine bleeding. We also studied the PFDE syndrome in the presence of dysfunctional uterine bleeding. In this study we reviewed the three procedures and assessed their results. We conclude that contact microhysteroscopy is a reliable diagnostic procedure, and should be considered part of diagnostic hysteroscopy, not an independent technique.

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.

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.

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.

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.

Hysteroscopy is a reliable procedure not only for diagnosis, but also for office treatment of uterine pathologies that, until recently, required general or at least topical anesthesia. The vaginoscopic approach without a speculum and tenaculum avoids discomfort to patients and ensures complete compliance. We treated 253 endometrial and cervical polyps with 5F instruments and an office hysteroscope with operative sheath. All polyps were removed on diagnosis, and the women were able to resume their normal activity soon after the procedure. Pretreatment with danazol or gonadotropin-releasing hormone analogs was necessary only for polyps larger than 2 cm. Recurrence at follow-up was 5%.

The development oflineage specific monoclonal antibodies has provided a means of identifying lymphoid lineage and the particular stage of differentiation of the leukemic cells [1–3]. Moreover, the application of several sophisticated investigations (dual fluorescence analysis, cytogenetic and genotypical studies) has led to a number of reports describing acute leukemias with the characteristics of two or more hematopoietic lineages [4–7]. A large number of studies analysing the expression of myeloid associated antigens (CD 13, CD33) in ALL (My + ALL) and T lymphoid antigens (CD2, CD3) in acute myeloblastic leukaemia (AML) [8–10) have been reported. Some Authors [11–14J have already emphasized the clinical significance of the co expression of myeloid and lymphoid antigens in the leukemic cells. This report describes the immunological characteristics of leukemic cells from a series of 68 ALL patients observed in our institution, evaluating a) the ALL immunophenotype at diagnosis and in relapse, and b) the possible prognostic significance of the expression of myeloid-associated antigens in ALL cells.

Despite an improved remission rate in patients with acute leukemia (AL) following the introduction of intensive chemotherapy programs, the incidence of relapsed and refractory patients still remains an important clinical problem. High-dose cytosine arabinoside (ARA-C) has been employed in patients with refractory or relapsed acute leukemia, alone or in combination with asparaginase [1], amsacrine [2] or idarubicin [3]. Recently, several clinical studies, investigating the combined use of mitoxantrone (MITOX) and ARA-C, have shown encouraging results in the treatment of relapsed or refractory acute leukemia [4–7]. In this work, we have investigated the efficacy and toxicity of MITOX in combination with continuous infusion of ARA-C in patients with refractory and relapsed acute leukemia.

Endometrial hyperplasia is considered to be a frequent cause of menorrhagia. Traditionally, this pathology was diagnosed from specimens obtained by uterine curettage or after hysterectomy for benign disease. With hysteroscopy one can visualize the uterine cavity directly and perform guided biopsies of the endometrial mucosa. We assessed the reliability of hysteroscopic procedures in the diagnosis of endometrial hyperplasia. We performed 980 hysteroscopies in 3 years for menorrhagia and found endometrial hyperplasia in 128 women. We compared the results with histologic findings. Statistical analysis was performed according to McNemar test. On the basis of the results, hysteroscopy diagnoses and monitors endometrial hyperplasia.

Infertility and menorrhagia in menopausal women are the most frequent indications for hysteroscopy. Often, however, the procedure turns out to be difficult or impossible due to stenosis and reduction in the size of the cervical canal. With the availability of more and more atraumatic endoscopic instrumentations and improvements in the technique, hysteroscopy can be performed in all women, whatever the obstacle. In our 5-year experience of 1500 hysteroscopies, we often found anatomic conditions that, besides being obstacles to performing the examination, increased patient discomfort. With the office hysteroscope with a 5F operative sheath one can rapidly overcome the obstacles and complete the examination without discomfort to the patient.