Ferritin: A Biomarker Requiring Caution in Clinical Decision.

OBJECTIVES: To determine the ferritin inter-assay differences between three "Conformité Européenne" (CE) marked tests, the impact on reference intervals (RI), and the proportion of individuals with iron deficiency (ID), we used plasma and serum from healthy blood donors (HBD) recruited in three different Switzerland regions. DESIGN AND METHODS: Heparinized plasma and serum from HBD were obtained from three different transfusion centers in Switzerland (Fribourg, Geneva, and Neuchatel). One hundred forty samples were recruited per center and per matrix, with a gender ratio of 50%, for a total of 420 HBD samples available per matrix. On both matrices, ferritin concentrations were quantified by three different laboratories using electrochemiluminescence (ECL), latex immunoturbidimetric assay (LIA), and luminescent oxygen channeling immunoassay (LOCI) assays, respectively. The degree of agreement between matrices and between the three sites/methods was assessed by Passing-Bablok and we evaluated the proportion of individuals deemed to have ID per method. RESULTS: Overall, no difference between serum and heparinized plasma ferritin values was observed according to Passing-Bablok analyses (proportional bias range: 1.0-3.0%; maximum constant bias: 1.84 µg/L). Significant median ferritin differences (p < 0.001 according to Kruskal-Wallis test) were observed between the three methods (i.e., 83.6 µg/L, 103.5 µg/L, and 62.1 µg/L for ECL, LIA, and LOCI in heparinized plasma, respectively), with proportional bias varying significantly between ±16% and ±32% on serum and from ±14% to ±35% on plasma with no sign of gender-related differences. Affecting the lower end of RI, the proportion of ID per method substantially varied between 4.76% (20/420) for ECL, 2.86% (12/420) for LIA, and 9.05% (38/420) for LOCI. CONCLUSIONS: Serum and heparinized plasma are exchangeable for ferritin assessment. However, the order of magnitude of ferritin differences across methods and HBD recruitment sites could lead to diagnostic errors if uniform RI were considered. Challenging the recently proposed use of uniform ferritin thresholds, our results highlight the importance of method- and region-specific RI for ferritin due to insufficient inter-assay harmonization. Failing to do so significantly impacts ID diagnosis.

High-sensitive cardiac troponin T as a marker of hemorrhagic complications in elderly patients anticoagulated for non-massive pulmonary embolism.

BACKGROUND: Recent data have raised concerns about the risk/benefit ratio of thrombolysis in non-high risk pulmonary embolism patients due to increased serious bleeding events. Whether cardiac biomarkers could be of help for bleeding risk stratification in this setting remains elusive. OBJECTIVES: To determine the prognostic accuracy of hs-cTnT, NT-proBNP, RIETE and PESI score for the occurrence of clinically relevant bleeding (CRB) in elderly patients under conventional anticoagulation therapy for non-massive pulmonary embolism (NMPE). METHODS: We evaluated 230 elderly patients with available blood sample taken within one day from diagnosis. The primary study endpoint was CRB at 1, 3 and 24 months. Prognostic accuracies and associations were determined using C-statistics and subhazard ratios (SHR), respectively. RESULTS: hs-cTnT displayed the highest discriminatory power at 1 month (C-statistics: 0.77, 95% CI: 0.68-0.88) which remained stable over time. Although C-statistics comparison indicated that hs-cTnT was not statistically superior to RIETE score (0.77 vs 0.67, p = 0.11), adding hs-cTnT to RIETE score significantly improved the C-statistics from 0.67 to 0.78 (p = 0.02). SHRs indicated that for each hs-cTnT log-unit increase, there was a 58% increase in the risk of CRB independently of the RIETE score (adjusted SHR: 1.58, 95% CI: 1.31-1.92). At the pre-specified cut-off of 14 ng/l, the negative predictive value of hs-cTnT was 96.9% (95% CI: 91.4-99.0) and 94.9 (95%CI: 88.6-97.8) at 1 and 3 months, respectively. CONCLUSION: In elderly, hs-cTnT provides incremental prognostic information over the RIETE score and could represent a valuable tool to identify NMPE patients at low risk of bleeding.

CRP-Based Cardiovascular Risk Assessment: New Conventional CRP Assay Fit for Purpose?

BACKGROUND: Subclinical inflammation was shown to play a role in the context of cardiovascular disorder processes. American College of Cardiology/American Heart Association guidelines on cardiovascular risk assessment in specific clinical contexts recommend the use of C-reactive protein (CRP) measurement with high sensitive (hs)-CRP assays that meet the precision requirements for values <2 mg/L. Until now, only hs-CRP assays reached the required limit of quantification. However, new regular CRP assays allow measuring CRP down to 0.6 mg/L. METHODS: A multisite comparative study between hs-CRP and a new conventional CRP assay (Tina-quant) was performed to evaluate the possibility of using regular CRP assays for cardiovascular risk assessment. RESULTS: A satisfactory concordance was observed between regular CRP assays and the hs-CRP assay. Both assays met the analytical precision requirements at the different cutpoints tested (1.00, 2.00, and 3.00 mg/L). CONCLUSION: These results suggest that this new regular CRP assay can be used for cardiovascular risk assessment, which is expected to provide substantial operational and financial advantages when compared with hs-CRP assays.

Impact of long distance rowing on biological health: A pilot study.

OBJECTIVES: To determine the impact of long distance rowing (160km, nonstop) on standard biological parameters and to study the relation between inflammation, myocardial necrosis, lipid profile, heart rate and energy expenditure. METHODS: Electrolytes, lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), procalcitonin (PCT), high-sensitive troponin T (hs-cTnT), and N-terminal pro-brain natriuretic peptide (NT-proBNP), were measured on non-fasting venous blood samples collected 8h before and after the rowing race on five healthy competitors. Heart rate and energy expenditure were measured using sporting self-measurement devices. RESULTS: After 16.5h of race, significant increases in median CRP (+25.2mg/l; p=0.04), IL-6 (+1.85pg/ml; p=0.04), TNF-α (+1.2pg/ml; p=0.04) and NT-proBNP levels (+88.8pg/ml; p=0.04) were observed, and a close to significant elevation for hs-cTnT(+6ng/l; p=0.06) and PCT (+0.14µg/l; p=0.07). On the other hand, significant decrease in median total cholesterol (-0.5mmol/l; p=0.04), triglycerides (-0.7mmol/l; p=0.04) were observed. Furthermore, significant correlations between the maximal heart rate reached during the race and CRP (r=0.90; p=0.03), IL-6 (r=0.90; p=0.03), and NT-proBNP (r=0.90; p=0.03) were observed, whereas no such associations were retrieved with median heart rate, the percentage of time passed over 70% of maximal heart rate or energy expenditure during the race. There was no association between PCT, NT-proBNP, hs-cTnT, inflammatory biomarkers, lipid profile or heart rate parameters. CONCLUSIONS: Long distance rowing induces inflammation and myocardial strain related to the maximal effort generated during the race, but has a favourable effect on lipid profile.

Allopurinol, oxidative stress and intestinal permeability in patients with cirrhosis: an open-label pilot study.

BACKGROUND: Cirrhosis is associated with intestinal barrier failure, related in part to enterocytes oxidative damage via xanthine oxidase overactivity. Experimentally, allopurinol, a xanthine oxidase inhibitor, reduces enterocytes' damage and bacterial translocation. AIM: To assess the short-term effects of allopurinol on intestinal permeability, oxidative stress and endotoxin-dependent cytokines in patients with cirrhosis. METHODS: Nineteen patients with cirrhosis, in a stable condition (age: 56 years; Child A/B/C: 6/7/6; ascites: 12; alcoholic cirrhosis: 16/19; abstinence >2 weeks), were included. At baseline and day 10 of allopurinol 400 mg/day, intestinal permeability [lactulose/mannitol (Lac/Man) ratio test], oxidative stress (serum malondialdehyde), as well as TNF-soluble receptor-1, IL-6 and lipopolysaccharide-binding protein (which reflects exposition to endotoxin) were measured. RESULTS: Malondialdehyde decreased significantly (-23%, P<0.05), whereas no effects were seen on intestinal permeability and the endotoxin-associated systemic inflammatory response. At baseline, portal pressure correlated to the Lac/Man ratio (r=0.55, P<0.02). At day 10, changes in malondialdehyde correlated to changes in the Lac/Man ratio (r=0.51, P<0.05). CONCLUSIONS: A 10-day course of allopurinol in patients with cirrhosis is associated with a significant reduction in oxidative stress but no effect on intestinal permeability and inflammatory markers. Whether intestinal damage in cirrhosis can be accessible to antioxidant therapy requires further study.

MODULAR ANALYTICS: A New Approach to Automation in the Clinical Laboratory.

MODULAR ANALYTICS (Roche Diagnostics) (MODULAR ANALYTICS, Elecsys and Cobas Integra are trademarks of a member of the Roche Group) represents a new approach to automation for the clinical chemistry laboratory. It consists of a control unit, a core unit with a bidirectional multitrack rack transportation system, and three distinct kinds of analytical modules: an ISE module, a P800 module (44 photometric tests, throughput of up to 800 tests/h), and a D2400 module (16 photometric tests, throughput up to 2400 tests/h). MODULAR ANALYTICS allows customised configurations for various laboratory workloads. The performance and practicability of MODULAR ANALYTICS were evaluated in an international multicentre study at 16 sites. Studies included precision, accuracy, analytical range, carry-over, and workflow assessment. More than 700 000 results were obtained during the course of the study. Median between-day CVs were typically less than 3% for clinical chemistries and less than 6% for homogeneous immunoassays. Median recoveries for nearly all standardised reference materials were within 5% of assigned values. Method comparisons versus current existing routine instrumentation were clinically acceptable in all cases. During the workflow studies, the work from three to four single workstations was transferred to MODULAR ANALYTICS, which offered over 100 possible methods, with reduction in sample splitting, handling errors, and turnaround time. Typical sample processing time on MODULAR ANALYTICS was less than 30 minutes, an improvement from the current laboratory systems. By combining multiple analytic units in flexible ways, MODULAR ANALYTICS met diverse laboratory needs and offered improvement in workflow over current laboratory situations. It increased overall efficiency while maintaining (or improving) quality.