Elevated Levels of Procalcitonin and Interleukin-6 are Linked with Postoperative Complications in Cardiac Surgery.

BACKGROUND: Cardiac surgery-associated acute kidney injury is a frequent and serious postoperative complication of cardiac surgery and is associated with an increased risk of morbidity, mortality, and length stay. In this study, we hypothesized that persistent elevation in inflammation in the first 48 h might be a powerful predictor of clinical outcome. Our aim was to elucidate the usefulness of interleukin-6 and procalcitonin postoperative levels in predicting mortality and renal complications in cardiac surgery patients. METHODS: A total of 122 cardiac surgery patients were enrolled. Procalcitonin and interleukin-6 concentrations were measured on the second postoperative day, and their levels were evaluated versus a number of conditions and endpoints. RESULTS: Procalcitonin has a good predictive value for adverse renal outcome (p < 0.05). Interleukin-6 has a good predictive value for 30 days and overall mortality in cardiac surgery population (p < 0.05). We did not observe a significant difference in procalcitonin and interleukin-6 levels among patients with different types of surgery and different extracorporeal circulation time, but the levels of both the molecules increase significantly depending on number of transfusions received by patients (p < 0.01). CONCLUSION: We speculated that procalcitonin and interleukin-6 could be two effective biomarkers. There is a possibility of having a combined inflammatory multi-biomarker panel, with procalcitonin for predicting renal outcome and interleukin-6 for predicting mortality.

TSH receptor autoantibody immunoassay in patients with Graves' disease: improvement of diagnostic accuracy over different generations of methods. Systematic review and meta-analysis.

BACKGROUND: TSH receptor antibodies (TRAb) are the diagnostic hallmark of Graves' disease (GD) and immunoassays for their detection have been available for more than 30 years over three generations of laboratory methods. Despite a growing body of data produced by clinical and laboratory research which demonstrates its elevated sensitivity and specificity, TRAb testing is poorly used for diagnosing GD. The aim of our systematic review and meta-analysis is to verify the diagnostic performance of TRAb detected with 2nd and 3rd generation immunoassay methods. METHODS: We searched for English articles using MEDLINE with the search terms "TSH receptor antibody assay", "TSH Receptor antibody tests" and "Graves' disease". We analyzed studies reporting on TSH receptor antibody tests performed by quantitative immunoassays, on untreated patients with GD as the index disease (sensitivity) and on a control group of either healthy subjects or patients affected by other thyroid diseases (specificity). A total of 681 titles were initially identified with the search strategy described. 560 publications were excluded based on abstract and title. Full-text review was undertaken as the next step on 111 publications providing data on TRAb testing; 58 articles were subsequently excluded because they did not include untreated GD patients, or used either bioassays or 1st generation immunoassays. 32 were also excluded because they included data only on sensitivity or only on specificity of the assay, or were duplicates. Finally, 21 articles were selected for meta-analysis. Extraction of data from selected articles was performed by two authors independently, using predefined criteria: the number of patients with GD and the number of healthy or diseased controls; specification of the analytical method used to detect TRAb; sensitivity and specificity of the assay. RESULTS: The meta-analysis showed that the overall pooled sensitivity and specificity of the 2nd and 3rd generation TRAb assays are 97.1% and 97.4%, and 98.3% and 99.2%, respectively, with little difference between the types of immunoassay methods employed (human or porcine receptor, manual or automated procedure). The likelihood of a TRAb-positive individual to have GD is 1367- to 3420-fold greater (depending upon the type of assay) compared to a TRAb-negative person. CONCLUSIONS: Data from the meta-analysis showed that TRAb measured with 2nd and 3rd generation immunoassay methods have very high sensitivity and specificity in the diagnosis of GD. The difference between 2nd and 3rd generation methods is small and is equally useful. In contrast with recommendations made by clinical endocrinologists who are not familiar with the state of the art in diagnostic technologies of autoimmunology laboratories, we propose a wide application of these tests in clinical practice to screen all hyperthyroid patients.

Comparison of estimated glomerular filtration rate (eGFR) using the MDRD and CKD-EPI equations for CKD screening in a large population.

BACKGROUND/AIMS: recently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) proposed a new equation for estimating glomerular filtration rate (eGFR), which could potentially replace the Modified Diet for Renal Disease Study (MDRD) equation in routine clinical use. Our aim was to evaluate the correlation between them and to compare the prevalence of each CKD stage using these two equations. METHODS: we measured serum creatinine in 38,188 consecutive patients and calculated eGFR using the CKD-EPI and MDRD equations. We also compared the distribution of CKD stages for both equations. RESULTS: there was very good correlation between eGFR estimated by CKD-EPI and MDRD at values < 60 ml/min × 1.73 m2, but not at higher values. Estimated prevalence of CKD (eGFR < 60 ml/min × 1.73 m2) was 5.9% with CKD-EPI and 7.5% with MDRD. Furthermore, the prevalence of CKD Stage 2 was lower with CKD-EPI (33.8% vs. 49.1%. with MDRD). CONCLUSION: the use of the CKD-EPI equation results in a lower estimated prevalence of CKD, compared to the MDRD equation. This may have important implications for public health and clinical practice, as well as for future modification of guidelines for laboratories.

An electronic thesaurus of Evidence Based Laboratory Medicine hematological and biochemical diagnostic tests.

The adoption of Evidence Based Laboratory Medicine (EBLM) has been hampered until today by the lack of effective tools. The SIMeL EBLM e-Thesaurus (on-line Repertoire of the diagnostic effectiveness of the laboratory, radiology and cardiology test) provides a useful support to clinical laboratory professionals and to clinicians for the interpretation of the diagnostic tests. The e-Thesaurus is an application developed using Microsoft Active Server Pages technology and carried out with Web Server Microsoft Internet Information Server and is available at the SIMeL website using a browser running JavaScript scripts (Internet Explorer is recommended). It contains a database (in Italian, English and Spanish) of the sensitivity and specificity (including the 95% confidence interval), the positive and negative likelihood ratios, the Diagnostic Odds Ratio and the Number Needed to Diagnose of more than 2000 diagnostic (most laboratory but also cardiology and radiology) tests. The e-Thesaurus improves the previous SIMeL paper and CD Thesaurus; its main features are a three languages search and a continuous and an easy updating capability.

Interchangeability and diagnostic accuracy of two assays for total and free prostate-specific antigen: two not always related items.

The variation between different PSA assays seems to influence the interpretation of individual PSA values and the clinical decisions about prostate cancer. One reason for this variability could be the different reactivity of antibodies for the various molecular forms of serum PSA; as a result, samples containing the same amount of tPSA but different proportions of fPSA can produce very different values. In this study, serum samples were collected prospectively from 152 consecutive patients referred to 2 institutions (Regional Hospital, Venice, 90 subjects; San Bortolo Hospital, Vicenza, 62 subjects) for PSA elevation and/or symptoms. Serum samples were assessed according to the manufacturers' instructions on the following 2 analyzers: the Immulite 2000 assay (Diagnostic Products Corporation, Los Angeles, USA), which measures tPSA and fPSA, and the ADVIA Centaur (Bayer Diagnostics, Tarrytown, USA), which assays tPSA and cPSA. cPSA values were transformed into fPSA by the equation fPSA=tPSA-cPSA. When taking Immulite tPSA and f/tPSA values as 100%, ADVIA Centaur values were 92.6% and 122%, respectively, which means that 20% of patients would be classified differently according to the traditional biopsy cutoff. In conclusion, there are considerable differences between the 2 methods, which could affect clinical decisions.

External Quality Assessment of stat test intralaboratory turnaround times. Pilot study from the Members of the Working Group for the Standardization and Promotion of Turnaround Time Control under the Auspices of the Comitato Italiano per la Standardizzazione dei Metodi Ematologici e di Laboratorio.

We describe procedures, results and prospects of a pilot program in External Quality Assessment (EQA) of the stat test intralaboratory turnaround times. Our goals are to promote quality by systematic monitoring and comparison of performances by laboratories, continuous investigation into the state of the art of the processes from receipt of sample to transmission of results and creation of a data base for standardization of measures and definition of consensus values for turnaround time. Of 30 laboratories invited to participate, 25 took part, agreeing to record times of arrival and transmission for all determinations of three analytes (blood hemoglobin, serum/plasma potassium and plasma prothrombin time) for seven consecutive days and to continue for one or more further periods of seven days as necessary if there were less than 300 determinations for each analyte. Within a preset time limit, data were sent by e-mail on an Excel file and we sent back two reports per analyte, showing: i) the graph for time vs. percentage of tests completed and several measures of turnaround time; ii) results of all laboratories in graph form, allowing each laboratory to identify only its own data. The high proportion of participating laboratories among those invited (83%) encourages us to implement the EQA program systematically, on a half-yearly basis, extending it to all laboratories wishing to participate in Italy or elsewhere in Europe.

Free radicals and oxidative stress challenge dialysis patients: effects of two different membranes.

Patients with end-stage renal disease (ESRD) who undergo hemodialysis manifest pronounced oxidative stress (OS), for the antioxidant system is inadequate to correct the imbalance between generation and scavenging of reactive oxygen species (ROS). To clarify the role of two different membranes on the OS, we measured plasma lipid peroxidation (LPO) and erythrocyte concentration of several antioxidant enzymes on 20 controls and 6 patients on bicarbonate dialysis (BHD). At 7 days intervals, 2 BHD sessions were done on the same 6 hemodialysis patients: the two BHD sessions were similar, except for the membrane used (cuprophan, first study; regenerated cellulose = Bioflux, second study, 7 days later). Before, during, and after each session (0', 30', 60', 120', end, 30' after BHD end), several blood samples were drawn. Lipid peroxidation and erythrocyte glutathione (GSH), superoxide dismutase (SOD), and catalase were spectrophotometrically determined (Bioxytech, France), but for erythrocyte glutathione peroxidase (Gpx) and G-6-PD, Gunzler's and Beutler's methods were used, respectively. Both membranes induce a significant decrease in LPO (p < 0.01) and an increase in erythrocyte SOD (p < 0.05). Bioflux shows some peculiar effects: a significant increase in erythrocyte GSH (p < 0.05) and erythrocyte catalase (p < 0.01) with a gradual increase of erythrocyte SOD and catalase/SOD ratio. Cuprophan, on the contrary, causes a sudden increase in erythrocyte SOD, while erythrocyte catalase decreases. These data support the view that Bioflux induces an OS lower than cuprophan because with the former, increased H2O2 production leads (thanks to catalase and GPx action) to water generation. With cuprophan, instead the reduced SOD/catalase ratio causes a greater H2O2 generation and a lower conversion to water.

Estimating mean pulmonary wedge pressure in patients with chronic atrial fibrillation from transthoracic Doppler indexes of mitral and pulmonary venous flow velocity.

OBJECTIVES: We sought to obtain a noninvasive estimation of mean pulmonary wedge pressure (MPWP) in patients with chronic atrial fibrillation (AF). BACKGROUND: It has previously been demonstrated that MPWP can be reliably estimated from Doppler indexes of mitral and pulmonary venous flow (PVF) in patients with sinus rhythm. Doppler estimation of MPWP has not been validated in patients with AF. METHODS: MPWP was correlated with variables of mitral and pulmonary venous flow velocity as assessed by Doppler transthoracic echocardiography in 35 consecutive patients. The derived algorithm was prospectively tested in 23 additional patients. RESULTS: In all patients the mitral flow pattern showed only a diastolic forward component. A significant but relatively weak correlation (r = -0.50) was observed between MPWP and mitral deceleration time. In 12 (34%) of 35 patients, the pulmonary vein flow tracing demonstrated only a diastolic forward component; a diastolic and late systolic forward flow was noted in the remaining 23 patients (66%). A strong negative correlation was observed between MPWP and the normalized duration of the diastolic flow (r = -0.80) and its initial deceleration slope time (r = -0.91). Deceleration time > 220 ms predicted MPWP < or = 12 mm Hg with 100% sensitivity and 100% specificity. When estimating MPWP by using the equation MPWP = -94.261 PVF deceleration time -9.831 Interval QRS to onset of diastolic PVF -16.337 Duration of PVF + 44.261, the measured and predicted MPWP closely agreed with a mean difference of -0.85 mm Hg. The 95% confidence limits were 4.8 and -6.1 mm Hg. CONCLUSIONS: In patients with chronic AF, MPWP can be estimated from transthoracic Doppler study of PVF velocity signals.

The role of erythrocytes in the deperoxidative processes in people on hemodialysis.

The defenses against the production of free radicals and reactive oxygen species (ROS) are to be found in plasma (ascorbate, urate, alpha tocopherol) and in erythrocytes (superoxide dismutase or SOD; catalase or CAT; glutathione peroxidase or GPx). In chronic renal failure, an increased lipid peroxidation and a reduced antioxidant activity seem to be present, but previous reports are conflicting. To clarify the peroxidative status and the defense mechanisms taking place in patients on dialysis, in 30 patients on dialysis (15 men, 15 women) and in 20 control subjects (10 men, 10 women), the following parameters were measured: plasma 4-hydroxinonenal (4-HNE) and erythrocyte reduced glutathione (GSH), SOD, GPx, and glucose-6-phosphate dehydrogenase (G-6-PD). Patients on dialysis, in comparison with control subjects, had 1) increased levels of 4-HNE (p < 0.001); 2) a significant increase in erythrocyte-GSH (p < 0.05); and 3) significant decreases in erythrocyte-SOD (p < 0.001), erythrocyte-G-6-PD (p < 0.005), and the erythrocyte-SOD/GPx ratio (p < 0.001). The dialysis procedure induced a certain reduction in plasma 4-HNE, an increase in erythrocyte-SOD activity, and an important consumption of erythrocyte-GSH, while the erythrocyte-SOD/GPx ratio changed. The current study supports the view that 1) erythrocytes act as small detoxifying packets; 2) in chronic renal failure, the antioxidant system is largely inadequate; and 3) in patients on dialysis, the antioxidant mechanism of erythrocytes in scavenging ROS is effectively exerted during dialysis but remains largely inadequate, as signs of lipid peroxidation persist with time.

Serum paraoxonase activity is decreased in uremic patients.

Paraoxonase is a high-density lipoprotein (HDL)-associated enzyme capable of hydrolysing lipid peroxides. We measured the activity of serum paraoxonase together with serum concentrations of a variety of lipid constituents--total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL), cholesterol, triglycerides, apolipoproteins A-I and B--in 60 hemodialyzed (HD) patients. We found that the paraoxonase activity was significantly reduced in HD patients compared with 64 healthy controls (mean median and interquartile values: 93, 63, 87 IU/l in HD patients and 151, 120 and 135 IU/l in controls). In patients, the trimodal frequency of distribution of paraoxonase activity showed a shift toward lower levels. The effect of NaCl on enzyme activation was more pronounced in the patient group, as compared with controls, suggesting a higher frequency of the B allozyme (more responsive to NaCl) in this population. We suggest that altered HDL subfraction, present in HD patients, may be the main cause of the widespread depression of paraoxonase. Furthermore, the higher frequency of allozyme B among HD patients might increase the risk of coronary artery disease. In conclusion, paraoxonase activity may be an adjunctive index of altered lipoprotein metabolism with important repercussions on atherosclerosis.