Verifying measurements on Siemens Atellica® instruments using clinically acceptable analytical performance specifications.

Measurements on clinical chemistry analysers must be verified to demonstrate applicability to their intended clinical use. We verified the performance of measurements on the Siemens Atellica® Solution chemistry analysers against the clinically acceptable analytical performance specifications, CAAPS, including the component of intra-individual biological variation, CVI. The relative standard uncertainty of measurement, i.e. analytical variation, CVA, was estimated for six example measurands, haemoglobin A1c in whole blood (B-HbA1c), albumin in urine (U-Alb), and the following measurands in plasma: sodium (P-Na), pancreatic amylase (P-AmylP), low-density lipoprotein cholesterol (P-LDL-C), and creatinine (P-Crea). Experimental CVA was calculated from single-instrument imprecision using control samples, variation between measurements on parallel instruments, and estimation of bias with pooled patient specimens. Each obtained CVA was compared with previously developed CAAPS. The calculated CVA was 1.4% for B-HbA1c (CAAPS 1.9% for single diagnostic testing, CAAPS 2.0% for monitoring after duplicate tests; IFCC units), 10.9% for U-Alb (CAAPS 44.9%), 1.2% for P-Na (CAAPS 0.6%, after triplicate testing 1.5%), 8.2% for P-AmylP (CAAPS 22.9%). The CVA was 4.9% for P-LDL-C (CAAPS for cardiovascular risk stratification 4.9% after four replicates), and 4.2% for P-Crea (CAAPS 8.0%). Three of the six measurands fulfilled the estimated clinical need. Results from P-Na measurements indicate a general need for improving the P-Na assays for emergency patients. It is necessary to consider CVI when creating diagnostic targets for laboratory tests, as emphasised by the CAAPS estimates of B-HbA1c and P-LDL-C.

Changing Immunochemistry Platforms: Thyroid Function Test Comparison and Reference Intervals Based on Clinical Needs.

BACKGROUND: Diagnosis of thyroid dysfunction relies on thyroid stimulating hormone (TSH), free thyroxine (FT4), and free tri-iodothyronine (FT3) tests against valid reference intervals (RIs). We changed the immunoassay platform from Abbott Architect to Siemens Atellica and aimed to establish Atellica RIs based on laboratory information system (LIS) patient data. METHODS: Atellica thyroid hormone immunoassays were verified against those of Architect. Real-life patient results were retrieved from LIS. A single result per patient dataset was used to establish the RIs by the indirect method. RESULTS: Atellica and Architect assays correlated well but Atellica showed a positive bias between 13% and 53%, the largest for FT4. Variations of the Atellica assays were ≤4%. The 95% Atellica RIs were 0.4-3.8 mU/L for TSH, 0.9-1.6 ng/dL for FT4, and 227-416 pg/dL for FT3. Considering the accumulating clinical experience with Atellica, the RIs for clinical use were adjusted as 0.5-4.0 mU/L, 0.9-1.8 ng/dL, and 169-409 pg/dL, respectively. CONCLUSIONS: We verified thyroid hormone RIs for Atellica by the indirect method for the first time. Our model proved reliable for selecting results of presumably healthy individuals from LIS data. Critical review of the RIs with local endocrinologists is essential.

Evaluation of OneTouch Verio(®), a new blood glucose self-monitoring system for patients with diabetes.

INTRODUCTION: Self-monitoring of blood glucose (SMBG) is important in diabetes management. Reliable and user-friendly instruments are essential. OneTouch Verio(®) is a new blood glucose concentration-measuring system designed to be used by patients with diabetes and healthcare professionals. The objective of the present study was to evaluate the analytical performance of the OneTouch Verio(®). METHOD: The OneTouch Verio(®) was evaluated by the Scandinavian evaluation of laboratory equipment for primary healthcare (SKUP) according to a protocol based on ISO 15197 and the American Diabetes Association (ADA) quality goals. Blood samples were collected and measured on the OneTouch Verio(®) by laboratory personnel and patients with diabetes (n = 91, randomized into groups receiving personal training or mail instructions for the OneTouch Verio(®) system). Results were compared to a validated routine method, imprecision and bias were calculated. User-friendliness was evaluated with a questionnaire. RESULTS: Quality specifications for blood glucose concentration monitoring systems according to ISO 15197 were fulfilled. The mean coefficients of variation (CV%) of repeatability was 3.4% when tested by laboratory personnel and within the goal of imprecision suggested by ADA. Mean CV% of repeatability for patient self-monitoring was 5.0% and 5.1% in the training- and the mail group, respectively. Total error was 6.4-10.0%. The OneTouch Verio(®) showed no hematocrit interference or variation between strip lots. CONCLUSION: The OneTouch Verio(®) displayed sufficient analytical quality and satisfactory user-friendliness. It is suitable for point-of-care testing of blood glucose concentration when handled by patients and healthcare professionals.

Analysis of human chorionic gonadotropin (hCG): application of routine immunological methods for initial testing and confirmation analysis in doping control.

Human chorionic gonadotropin (hCG) is dimeric glycoprotein produced by placenta in pregnancy and also in low levels by pituitary gland. The main clinical use for exogenous hCG-administration is typically linked to infertility. The desired effect of hCG misuse in sport is due to the enhancement of testicular production of testosterone. Therefore, hCG is listed by the World Anti-Doping Agency (WADA) as a prohibited substance in male athletes and according to the recently published WADA guideline urinary concentrations of hCG > 5 IU/L may be an indicator of doping. In this study two independent immunoassays were used to implement the new WADA guideline. The assay for initial testing (Siemens Immulite 2000 XPi hCG assay) recognizes various hCG variants (e.g. hCG and ß-core fragment of hCG) whereas the confirmatory assay (PerkinElmer DELFIA Xpress hCG) is sensitive to intact and nicked hCG only. Both assays showed adequate sensitivity and were proven fit-for-purpose in routine doping control. Population-based distribution of the assays was in good agreement with results of earlier studies and supported well the current threshold of 5 IU/L.

Viral oncogene-induced DNA damage response is activated in Kaposi sarcoma tumorigenesis.

Kaposi sarcoma is a tumor consisting of Kaposi sarcoma herpesvirus (KSHV)-infected tumor cells that express endothelial cell (EC) markers and viral genes like v-cyclin, vFLIP, and LANA. Despite a strong link between KSHV infection and certain neoplasms, de novo virus infection of human primary cells does not readily lead to cellular transformation. We have studied the consequences of expression of v-cyclin in primary and immortalized human dermal microvascular ECs. We show that v-cyclin, which is a homolog of cellular D-type cyclins, induces replicative stress in ECs, which leads to senescence and activation of the DNA damage response. We find that antiproliferative checkpoints are activated upon KSHV infection of ECs, and in early-stage but not late-stage lesions of clinical Kaposi sarcoma specimens. These are some of the first results suggesting that DNA damage checkpoint response also functions as an anticancer barrier in virally induced cancers.

Gata3 is required for early morphogenesis and Fgf10 expression during otic development.

Inner ear develops from an induced surface ectoderm placode that invaginates and closes to form the otic vesicle, which then undergoes a complex morphogenetic process to form the membranous labyrinth. Inner ear morphogenesis is severely affected in Gata3 deficient mouse embryos, but the onset and basis of the phenotype has not been known. We show here that Gata3 deficiency leads to severe and unique abnormalities during otic placode invagination. The invagination problems are accompanied often by the formation of a morphological boundary between the dorsal and ventral otic cup and by the precocious appearance of dorsal endolymphatic characteristics. In addition, the endolymphatic domain often detaches from the rest of the otic epithelium during epithelial closure. The expression of several cell adhesion mediating genes is altered in Gata3 deficient ears suggesting that Gata3 controls adhesion and morphogenetic movements in early otic epithelium. Inactivation of Gata3 leads also to a loss of Fgf10 expression in otic epithelium and auditory ganglion demonstrating that Gata3 is an important regulator of Fgf-signalling during otic development.