Preoperative Plasma Levels of Total Testosterone Associated with High Grade Pathology-Detected Prostate Cancer: Preliminary Results of a Prospective Study in a Contemporary Cohort of Patients.

OBJECTIVES: To investigate the associations, if any, between preoperative plasma levels of total testosterone (TT) and pathology Gleason score (pGS) in a contemporary cohort of prostate cancer (PCa) patients. MATERIALS AND METHODS: Between November 2014 and June 2015, plasma levels of TT were measured in 142 patients who underwent radical prostatectomy. Exclusion criteria were as follows: 5α-reductase inhibitors, LH-releasing hormone analogues, or testosterone replacement treatment. The entire cohort, assessed by continuous and categorical variables, was classified into two groups according to the pGS that included low-intermediate (pGS 6-7) and high grade (pGS > 7) cases. TT was evaluated as a continuous variable. RESULTS: The cohort included 128 cases. High grade PCa was detected in 28 (21.8%) patients. Median plasma levels of both TT and prostate specific antigen (PSA) were significantly higher in these cases. In the clinical multivariate model, independent and positive predictors of pGS > 7 were TT (p = 0.041; OR = 1.004), PSA (p = 0.006; OR = 1.191), and bGS > 6 (p = 0.004; OR = 5.0); that is, a single unit increase in TT plasma levels increases the odds of having high grade PCa by 4%. CONCLUSION: In a contemporary cohort of patients, preoperative plasma levels of TT directly and independently associated with high grade PCa. High baseline plasma levels of TT might have clinical applications for managing PCa. New and well designed prospective studies dealing with this subject are required.

Troponin I measured with a high sensitivity immunoassay is significantly increased after a half marathon run.

Only a few studies have assessed the kinetics of cardiac troponins after endurance exercise by using the novel high-sensitive (HS) immunoassays. These were based on the measurement of HS-TroponinT (TnT), but not HS-Troponin I (TnI), and exclusively involved marathon or ultra-marathon contests. TnI was measured in 17 healthy trained Caucasian males performing a 21 km, half-marathon, with the conventional AccuTnI and the HS-AccuTnI immunoassays. The concentration of HS-AccuTnI significantly increased from the mean baseline value of 2.9 ng/L (Interquartile range [IQR], 2.4- 4.3 ng/L) to 4.8 (IQR, 3.0-5.7 ng/L) after the run (p = 0.002), 9.0 ng/L (IQR, 5.8-15.3 ng/L) at 3h (p < 0.001), 12.3 ng/L (IQR, 7.1-21.5 ng/L) at 6h (p < 0.001), and 4.5 ng/L (IQR, 2.8-6.0 ng/L) at 24 h (p = 0.003) afterwards. The variation throughout the study period was statistically significant (p < 0.001). Age, training history, finishing time and exercise intensity were not associated with changes of HS-AccuTnI. The values of the TnI measured with the conventional AccuTnI immunoassay were always below the 99th percentile reference limit, except in one subject 3 h after the run, and in two subjects 6 h after the run. These results attest that TnI values measured with the novel HS-AccuTnI immunoassay were significantly increased in athletes participating in a half marathon.

Analytical performance of the new ACL AcuStar HemosIL D-Dimer.

Several lines of clinical evidence as well as guidelines and recommendations suggest that the overall diagnostic performance of D-dimer testing outstrips that of any other biomarker in the diagnostic approach of patients with venous thromboembolism or disseminated intravascular coagulation. Along with specific technical characteristics, the analytical performance of each D-dimer immunoassay should, however, be assessed before implementation in clinical practice. The aim of this study was to evaluate the analytical performance of HemosIL AcuStar D-Dimer immunoassay, a novel chemiluminescent immunoassay specifically designed for the instrument Instrumentation Laboratory ACL AcuStar. The within and between-run imprecision (n = 20) was comprised between 3.6 and 5.8%. The linearity was excellent up to 16 200 ng/ml (r = 1.00; P < 0.001), and optimal between 224 and 69 900 ng/ml (r = 0.992; P < 0.001). A significant agreement of values was observed between HemosIL AcuStar D-Dimer and HemosIL D-Dimer HS for ACL TOP (r = 0.884; P < 0.001), as well as with Vidas D-Dimer (r = 0.791; P < 0.001). Results of HemosIL AcuStar D-Dimer displayed a modest negative bias as compared with those of Vidas D-dimer (mean bias -22%; 95% Confidence Interval, -122% to 49%). The analytical accuracy assessed against Vidas D-dimer also yielded an area under the curve of 0.998 (P < 0.001). As regards, the preliminary definition of cutoff value, optimal sensitivity (100%) and specificity (96%) were found at a diagnostic threshold of 466 ng/ml. The results of this investigation attest that the novel HemosIL AcuStar D-Dimer is characterized by remarkable accuracy and precision, optimal linearity and excellent agreement with the reference immunoassay. As such, its technical and analytical performance would make it a suitable method for the rapid and accurate quantification of D-dimer in clinical laboratories.

Inherited and acquired factor V deficiency.

The clotting factor V, also known as proaccelerin or labile factor, is synthesized by the liver and possibly by the megakaryocytes. Factor V exerts a pivotal role in hemostasis, as it participates in both procoagulant and anticoagulant pathways, being an essential cofactor of the prothrombinase complex in the former case and participating in the inactivation of factor VIII (FVIII) in the latter. Isolated factor V deficiency due to mutations in the F5 gene is a rare inherited coagulopathy typically associated with a broad spectrum of bleeding symptoms, ranging from easy bruising, delayed bleeding after haemostatic challenges such as trauma or surgery to more severe joint bleeds. The combined deficiency of factor V and FVIII, commonly known as F5F8D, is a recessive disorder not attributable to the association of isolated factor V and FVIII deficiencies, but rather to defective intracellular processing of both proteins due to mutations involving the LMAN1 and MCFD2 genes, which encode two proteins forming an essential cargo receptor complex. Overall, patients affected by F5F8D do not bleed more in terms of both frequency and severity than those carrying specific deficiencies of both factors and the bleeding phenotype is generally mild. Although now increasingly rare, inhibitors directed against factor V may also develop in individuals of any age and are characterized by a very heterogeneous clinical phenotype. The aim of the current review is to provide an overview on the physiopathology, diagnostics, and clinical management of both inherited and acquired factor V deficiency.

Serine/threonine kinase 39 is a candidate gene for primary hypertension especially in women: results from two cohort studies in Swedes.

BACKGROUND: As recently pinpointed by a genome-wide association study the serine/threonine kinase 39 (STK39) is a candidate gene for hypertension. This kinase is strongly implicated in sodium reabsorption by the kidney through its modulating effect on furosemide-sensitive and thiazide-sensitive channels. The aim of our study was to test the effects of the STK39 rs35929607A>G polymorphism on blood pressure (BP) levels and the prevalence and incidence of hypertension in middle-aged Swedes participating in two urban-based surveys in Malmö (Sweden). METHODS: The rs35929607A>G polymorphism was genotyped in 5634 participants included in the cardiovascular cohort of the 'Malmö Diet and Cancer-cardiovascular arm' (MDC-CVA) study and successively in 17 894 participants of the 'Malmö Preventive Project' (MPP) both at baseline and at reinvestigation after a mean of 23 years. The effect of the same single nucleotide polymorphism on salt sensitivity was tested in 39 participants of the Salt Reduction to Avoid Hypertension study. RESULTS: Both before and after adjustment for covariates, the functional rs35929607A>G polymorphism was associated with higher SBP and DBP values in the MDC-CVA, but not in the MPP. In both surveys, the polymorphism was associated with hypertension prevalence; after adjustment using the autosomal-dominant model, the odds ratio for hypertension ranged between 1.077 (MPP at baseline) and 1.151 (MDC-CVA) with P-value less than 0.05. After stratification for sex, the results remained statistically significant in women, but not in men. Carriers of the G-allele displayed an increase in salt sensitivity. CONCLUSION: Our results from two large cohort studies support previous evidence about the association of the STK39 rs35929607A>G variant with hypertension, especially in women. If further confirmed in successive studies, owing to its pivotal role in sodium reabsorption at the renal tubule level, STK39 might prove to be a suitable target for antihypertensive therapy. The greater effect of the STK39 rs35929607A>G polymorphism in women with respect to men deserves further investigation.

Performance of the automated and rapid HemosIL D-Dimer HS on the ACL TOP analyzer.

We evaluated the analytical performance of the new commercial HemosIL D-Dimer HS, a latex-enhanced turbidimetric immunoassay, from Instrumentation Laboratory for D-dimer measurement on the ACL TOP automated analyzer. The recommended cut-off for this immunoassay is 243 ng/ml. The within-run and between-run coefficients of variations of D-Dimer HS for low, intermediate and high D-dimer concentrations were: 3.3-6.6%, 2.3-2.6%, 2.4-3.2%, respectively. The assay was proven linear in a range of D-dimer concentrations comprised between 319 and 2274 ng/ml. Results of 171 citrated plasma samples were compared with those of the reference commercial immunoassay VIDAS D-Dimer. Although the nonparametric regression according to the method of Passing and Bablok and the relative Spearman's correlation coefficient were excellent (HemosIL D-Dimer HS = 1.30 x VIDAS - 384; r = 0.964, P < 0.001), some discrepancies could be observed in Bland-Altman plots analysis. On the basis of the present evaluation, we conclude that the analytical performance and the main technical features of new HemosIL D-Dimer HS assay make it a suitable method for the rapid quantification of D-dimer in clinical laboratories. Further studies are however needed to confirm the safety of the assay and to determine the most optimal cutoff level in patients with venous thromboembolism.

Prevalence and type of pre-analytical problems for inpatients samples in coagulation laboratory.

RATIONALE, AIMS AND OBJECTIVES: Total quality in coagulation testing is a necessary requisite to achieve clinically reliable results. Evidence was provided that poor standardization in the extra-analytical phases of the testing process has the greatest influence on test results, though little information is available so far on prevalence and type of pre-analytical variability in coagulation testing. METHODS: The present study was designed to describe all pre-analytical problems on inpatients routine and stat samples recorded in our coagulation laboratory over a 2-year period and clustered according to their source (hospital departments). RESULTS: Overall, pre-analytic problems were identified in 5.5% of the specimens. Although the highest frequency was observed for paediatric departments, in no case was the comparison of the prevalence among the different hospital departments statistically significant. The more frequent problems could be referred to samples not received in the laboratory following a doctor's order (49.3%), haemolysis (19.5%), clotting (14.2%) and inappropriate volume (13.7%). Specimens not received prevailed in the intensive care unit, surgical and clinical departments, whereas clotted and haemolysed specimens were those most frequently recorded from paediatric and emergency departments, respectively. The present investigation demonstrates a high prevalence of pre-analytical problems affecting samples for coagulation testing. CONCLUSIONS: Full implementation of a total quality system, encompassing a systematic error tracking system, is a valuable tool to achieve meaningful information on the local pre-analytic processes most susceptible to errors, enabling considerations on specific responsibilities and providing the ideal basis for an efficient feedback within the hospital departments.