Multicenter evaluation of analytical performances of platelet counts and platelet parameters: Carryover, precision, and stability.

INTRODUCTION: The correctness of the results of automated platelet analysis is still highly debated. The aim of this multicenter study, conducted according to international guidelines, was to verify the analytical performance of nine different types of hematology analyzers (HAs) in the automated platelet analysis. METHODS: Four hundred eighty-six peripheral blood samples (PB), collected in K3 EDTA tubes, were analyzed by ABX Pentra, ADVIA2120i, BC-6800, BC-6800 Plus, Cell-DYN Sapphire, DxH800, XE-2100, XE-5000, XN-20 with PLT-F App. Within-run imprecision and between-run imprecision were carried out using PB and material control, respectively. The carryover, low limit of quantification (LoQ), and the PB stability were evaluated. RESULTS: The carryover was absent for all HAs. The LoQ of PLT ranged between 2.0 (Cell-Dyn Sapphire) and 25.0 × 109 /L (ADVIA 2120i), while immature platelet fraction (IPF) ranged between 1.0 (XN-20) and 12.0 × 109 /L (XE-5000). The imprecision (%CV) increases as the platelet count decreases. No HAs showed desirable CVAPS for PLT counts less than 50.0 × 109 /L, with the exception of Cell-DYN Sapphire (CV 3.0% with PLT-O mean value of 26.7 × 109 /L), XN-20 (CV 2.4% with PLT-F mean value of 21.5 × 109 /L), and BC-6800 Plus (CV 1.9% with PLT-O mean value of 26.5 × 109 /L). The sample stability ranged between under two hours for MPV by ADVIA2120i and 8 hours for other PLT parameters and HAs. CONCLUSION: The findings of this study may provide useful information regarding carryover, precision, and stability of platelet counts and parameters, especially in thrombocytopenic samples. Moreover, the stability of sample for platelet analysis is conditioned by the HA and by temperature and storage time.

Analytical validation of a highly sensitive point-of-care system for cardiac troponin I determination.

Background Highly sensitive cardiac troponin assays (hs-cTn) are not available as point-of-care (POC) measurements. As rapid testing cannot be achieved at the expense of clinical performance, there is an urgent need to develop and rigorously validate POC hs-cTn. Konica Minolta (KM) has recently developed a surface plasmon-field enhanced fluorescence spectroscopy-based POC hs-cTn I system. Methods We validated the analytical characteristics of the KM POC system according to the international guidelines. Results Limit of blank (LoB) and limit of detection (LoD) were 0.35 and 0.62 ng/L, respectively, hs-cTn I concentrations corresponding to a total CV of 20%, 10% and 5% were 1.5, 3.9 and 11.0 ng/L, respectively. Method comparison studies showed that KM calibration was successfully traced to higher-order references. Limit of quantitation (LoQ), i.e. the hs-cTn I concentration having a total error of measurement of ≤34%, was 10.0 ng/L. The upper reference limit (URL) for 600 healthy blood donors was calculated at 12.2 ng/L (90% confidence interval [CI]: 9.2-39.2), while sex-partitioned URLs were 20.6 (males) and 10.7 ng/L (females), respectively (p < 0.0001). KM assay measured hs-cTn I concentrations >LoD in 65.7% of all reference individuals, in 76.7% of males and in 54.7% of females, respectively. Conclusions The KM system joins the characteristics of POC systems to the analytical performance of hs-cTn.

Knee hyperextension and a small lateral condyle are associated with greater quantified antero-lateral rotatory instability in the patients with a complete anterior cruciate ligament (ACL) rupture.

PURPOSE: To identify factors associated with quantified rotatory stability (pivot-shift phenomenon) in the anterior cruciate ligament (ACL)-injured knee joint. METHODS: A consecutive sample of 54 patients who were diagnosed with an ACL injury and admitted to our hospital to undergo ACL reconstruction were enrolled in this study. Antero-lateral rotatory laxity of the knee joint was quantified using a Kinematic Rapid Assessment device (KiRA; Orthokey LTD) under spinal block before initiating reconstruction of the ACL. Univariate and multivariate regressions were performed assuming relationships between patient characteristics (independent variables) and quantified antero-lateral rotatory stability (a dependent variable). RESULTS: It was observed that a low BMI (t = - 1.659, n.s.), greater passive knee extension angle (t = 2.374, P = 0.023), and a narrower lateral femoral condyle width index (t = - 1.712, n.s.) could be candidates associated with the antero-lateral rotatory instability, using univariate analysis. Employing multivariate analysis controlling for these three variables, that the range of passive knee extension was found to be significantly associated with antero-lateral rotatory instability in the ACL-injured knee joint (t = 2.21, P = 0.035). Patients were then divided into two groups (pivot-shift negative versus positive groups) based on the KiRA-documented quantified pivot-shift test. Interestingly, 23.3% of patients were pivot-shift negative, even though their ACL was confirmed as a complete rupture by arthroscopic observations. The degree of passive knee extension was 2.3 ± 4.5 (mean ± SD) in the pivot-shift negative group, while it was 6.8 ± 6.6 in the pivot-shift positive group (n.s.). The lateral femoral condyle width index was 36.6 ± 2.0% in the pivot-shift negative group, and it was significantly wider than in the pivot-shift positive group (33.8 ± 2.6%, P = 0.0046). Finally, we estimated that the risk of positive pivot-shift depends on the degree of knee extension. The logistic regression analysis revealed that genu recurvatum significantly increased the odds ratio for positive pivot-shift (OR = 3.08, P = 0.047, 95% CI = 1.017-9.350). CONCLUSIONS: This study revealed that greater antero-lateral rotatory instability in patients with a complete ACL rupture was associated with genu recurvatum and small lateral femoral condyle. These factors should be considered as predictors of a poor outcome from an ACL reconstruction due to a higher load on the ACL graft, and therefore, the attending physicians should modify the treatment strategies accordingly. This study indicates that joint hyperlaxity and bone morphology contribute to the rotational stability of the knee joint, in addition to the ACL and antero-lateral complex (ALC). LEVEL OF EVIDENCE: IV.

Serum α-fetoprotein in pediatric oncology: not a children's tale.

Background Measurement of α-fetoprotein (AFP) concentrations in the serum of infants is useful for the management of testicular germ cell tumors, hepatoblastoma and hepatocellular carcinoma. Here, we provide a critical review of the available information about pediatric reference intervals (RI), focusing on their utility in interpreting AFP as an aid for cancer diagnosis. Content Evidence sources in the available literature were critically appraised. Out of 3873 retrieved papers, 24 were finally selected and carefully inspected, and six of them overcame exclusion criteria (i.e. methodological limitations in the study design, statistical gaps, drawbacks in traceability of the AFP assay to higher order materials and/or biased reporting of AFP results). Preterm and term infants up to the 3rd month of life exhibited the highest average AFP concentrations, but the attempt of defining RI by data pooling and partitioning for age intervals was impeded by the wide variability of data. The inability of defining robust RI in the first months of life made difficult, if not impossible, using upper reference limits for ruling out malignancies with a single AFP result. Evaluating the behavior of AFP concentrations 5 days from the baseline result, if this exceeds risk thresholds partitioned for age, according to the formula Xt=X0*2-t/HL (where: t=days elapsed for AFP retest; HL=AFP half-life according to age; X0=AFP baseline concentration, and Xt=predicted AFP concentration at day 5), could give a better information. Summary Novel studies defining AFP RI in infants based on robust methodology are warranted to improve the interpretation of AFP results in pediatric oncology. In the meantime, algorithms based on both serum AFP absolute concentrations and HL may aid in cancer diagnosis.

Serum human epididymis protein 4 vs. carbohydrate antigen 125 in ovarian cancer follow-up.

BACKGROUND: The addition of human epididymis protein 4 (HE4) to carbohydrate antigen 125 (CA125) in ovarian cancer (OC) assessment has been proposed. We compared the clinical value of biomarker changes in a prospective series of patients undergoing OC monitoring. METHODS: We studied 43 patients (79% post-menopausal), followed for 3.5 ±â€¯3.1 years. Serous OC was prevalent (53.5%), with 81.4% of patients diagnosed at late stages. Both cut-offs and reference change values (RCV) were used for assessing significant marker changes. RESULTS: The use of cut-offs for CA125 and HE4 interpretation appeared equally fitting the evaluation of disease progression defined according to running guidelines, performing better than RCV criterion. However, both markers were simultaneously over cut-offs only in 46% of samples and changed in agreement in 35% of cases. The inspection of individual longitudinal trends indicated as main causes of disagreement the influence of renal impairment on HE4 concentrations and the more significant rate of decrease of CA125 vs. HE4 concentrations early after treatment. CA125 and HE4 changes according to RCV were not predictive of OC progression. CONCLUSIONS: CA125 appears the most reliable biomarker for OC monitoring, whereas HE4 contributes additional information only in a minority of cases.

Tackling serum folate test in European countries within the health technology assessment paradigm: request appropriateness, assays and health outcomes.

Several authors have recently claimed an excess in serum folate test ordering, suggesting phasing out it from clinical use. According to studies performed in countries undergoing folic acid fortification policies, it is indeed no more cost-effective to test folate in the face of deficiency prevalence <1%. In this paper, we sought to evaluate request appropriateness, analytical issues, and cost-effectiveness of serum folate determination for clinical purposes in the European context, considering if evidence retrieved in fortified countries may be generalized. Studies performed in non-fortified countries have generally reported a suboptimal folate intake and suggest a remarkable prevalence of folate deficiency. Our internal data suggest that ~20%-25% of the subjects undergoing serum folate test are at risk for deficiency. However, a reliable evaluation of the risk for deficiency implies the knowledge of all issues related to the total testing process of folate measurement as well as the identification of the appropriate population in which to perform the test. The cost-effectiveness of the test is maximized when the request is oriented to subjects suggestive/at risk for deficiency, becoming low if the test is used as a screening tool or for monitoring of vitamin intake/supplementation. Because the individual folate status has a key role in ensuring normal development, physiologic growth, and maintenance of optimal health, the evaluation of its serum levels has to be retained in the clinical use in non-fortified countries, boosting for more appropriate request, and evidence from countries following fortification policies should be cautionary interpreted.