Volume 40, Issue s1 - Translations

The detection of autoantibodies is well established in daily clinical practice for evaluation of systemic autoimmune diseases like rheumatoid arthritis (RA), connective tissue diseases and vasculitides. Rheumatoid factor (RF) or the anti-citrullinated protein antibody (ACPA) is only observed in approximately 80% of patients suffering from rheumatoid arthritis. Anti-CarP autoantibodies might serve as a novel marker, filling this gap. The detection of anti-nuclear antibody (ANA) facilitates the diagnosis of connective tissue diseases. Elevated levels of anti-centromer antibodies, anti-topoisomerase I [anti-Scl-70] antibodies and the anti-RNA polymerase III antibodies, which belong to the group of ANA, are frequently present in the serum of patients suffering from systemic sclerosis and are therefore incorporated into the new classification criteria. To establish the diagnosis of an antiphospholipid syndrome, the detection of the lupus anticoagulant and the aCL-/anti-β2GPI-antibodies of IgG, IgM and IgA isotypes plays a pivotal role. The anti-neutrophil cytoplasmic antibodies (ANCAs) are associated with vasculitides of small vessels. Screening with immunofluorescence testing (IFT) is established as the first step followed by additional immunoassays specific for proteinase 3 (PR3) and myeloperoxidase (MPO) autoantibodies. Novel bedside test procedures for these antibodies allow an early diagnosis in critically ill patients. New biomarkers for polymyalgia rheumatic and for spondyloarthritides are also described, but their clinical relevance remains uncertain and necessitates further studies.

Diagnostic flow cytometry has been established in laboratory diagnostics as an indispensable, deeply specialized method. Because of the special needs of the analysis in vital cells, the introduction and maintenance of quality management systems stays a challenge. Meanwhile, experience has been collected for quality controls and validation in diagnostic flow cytometry. This will be summarized in this article. The focus will be on the relevant rules and regulations for diagnostic laboratories and the associated requirements for medical diagnostics, as well the guidelines of the German Medical Association, Bundesärztekammer , (RiliBÄK) and in particular the accreditation according to DIN EN ISO 15189. In detail, factors influencing flow cytometry analyses, strategies for the standardization and harmonization in flow cytometry, and possibilities for verification and validation in the flow cytometry laboratory are given. A summary of the most frequent quality problems rounds up this overview.

Background: Pediatric reference intervals for iron-related parameters are determined continuously over time from a highly standardized sample collection by application of the R-package generalized additive models for location, scale and shape (GAMLSS), which is little known in laboratory medicine. Methods: Two thousand seven hundred and seventy-eight samples from Leipzig research center for civilization diseases (LIFE) Child participants at the age of 2.5–19 years were analyzed on a Sysmex XN-9000 for hemoglobin and reticulocytes and on a Roche Cobas 8000 for transferrin and ferritin. Reference intervals were established by repeated model calculation by use of the LMS (λ-µ-σ) method from Cole with specifically weighted subsamples. Results: Continuous and gender-specific reference intervals as well as smoothed percentile curves were established for hemoglobin, ferritin, reticulocytes and transferrin. In the case of repeated model calculations, single curves and averaged percentile curves were shown. The single curves outlined potential variations of the different parameter trends. The averaged percentile curves submitted a stable assessment of curve trends over time for iron-related parameters in childhood and adolescence. Conclusions: For the first time current age- and gender- specific reference intervals are available by application of the R-package GAMLSS and the laboratory techniques applied here. Compared to earlier studies, previous findings can be completed and discrepancies related to different methodical approaches, can be pointed out. Relevant findings for the diagnosis of iron deficiency anemia, such as gender-dependent assessment of hemoglobin starting at the age of 11 instead of 15 [according to the World Health Organization (WHO)], are presented.

Background: The metabolic syndrome (MetS) is a cluster of metabolic changes which is associated with insulin resistance (IR). Cutoff values for the homeostasis model of insulin resistance (HOMA-IR) – a surrogate marker of IR-to identify subjects with MetS are not established. Methods: Cross-sectional data of 446 younger (53% women, 28±3 years old) and 1271 elderly study participants (52% women, 68±4 years old) without diabetes were available for the current analysis. MetS was defined according to the IDF/AHA/NHLBI (International Diabetes Federation/American Heart Association/National Heart, Lung, and Blood Institute) criteria of 2009. Using receiving operating characteristics (ROC) analysis cutoff values for HOMA-IR were calculated above which participants with MetS could be identified with highest sensitivity and specificity. Finally, binary logistic regression models were calculated. Results: The prevalence of MetS was 6.7% in young and 28.3% in elderly subjects. HOMA-IR cutoff values for the detection of MetS were HOMA-IR >1.88 (young subjects; sensitivity 80%, specificity 85.3%, positive predictive value 80%, negative predictive value 15%) and HOMAIR >1.98 (elderly subjects; sensitivity 73.6%, specificity 72.9%, positive predictive value 74%, negative predictive value 27%). In adjusted regression models [age, body mass index (BMI), sex, physical activity and age groups] subjects above these cutoff-values had odds of 5.7 [95% confidence interval (CI): 4.1–7.9] in elderly and 22.2 (95% CI: 7.0–70.5) in younger study participants to have MetS. Conclusions: Cutoff values for HOMA-IR are not established in clinical practice; however, they could be used to identify subjects with MetS, even if a diagnosis of MetS cannot made based solely on HOMA-IR considering the negative predictive values.

This review summarizes recent studies and evidence-based recommendations on management of thyroid disorders, including Graves’ disease and Graves’ orbitopathy, laboratory and clinical issues on hypothyroidism and its treatment, risk assessment of thyroid nodules and novel concepts for risk adapted management of thyroid cancer.

To date more than 400 medical laboratories in Germany are accredited based on DIN EN ISO 15189 (Medical laboratories – requirements for quality and competence). In Germany, a new version of the DIN EN ISO 15189 has been published in 2014. This standard includes overall criteria but no requirements specific for certain disciplines of laboratory medicine. The present study examined how technical requirements, mainly for quality assurance and analytic methods, influence the correctness of results in clinical virology. Experts from laboratories, industry, DAkkS (German Accreditation Body) and from standardization have been interviewed. The qualitative content analysis showed that fulfilling technical requirements increased the correctness of examination results and minimized the risks for patient care and safety. Furthermore, we studied how effective internal quality controls, assay-controls as well as additional controls, assure HIV-p24-antigen and anti-HBs results. Additional controls recommended by DIN EN ISO 15189 (so called “run controls”) clearly indicated inaccuracies of HIV antigen measurement that were undetected by manufacturer’s controls. Also for anti-HBs examination, such internal controls provided by the manufacturer did not guarantee correct results. Therefore, we conclude that fulfilling DIN EN ISO 15189, usually confirmed by accreditation, has a positive influence on correctness of results in clinical virology, ultimately improving patient care.

Cytologic examination of cerebrospinal fluid (CSF) is a technically simple, yet productive diagnostic procedure. The cytocentrifuge technique is the most commonly utilized method to concentrate the generally scant cellular components of CSF. There are several preanalytical and analytical pitfalls causing artefacts and making proper assessment of the CSF cell preparation more difficult or even impossible. The common cell types of CSF are lymphocytes and monocytes including their activated forms. Cytologic examination of inflammatory conditions puts emphasis on the cellular composition of CSF caused by bacterial infections compared to viral infections and noninfectious inflammatory diseases of the brain. Concerning non-neoplastic disorders, diagnosis of subarachnoidal hemorrhage is of special interest and a main field of application of CSF cytology. The cytology of neoplastic disorders encounters three typical constellations the investigator is usually confronted with: either a primary malignancy is already known and dissemination to the meninges shall be evaluated or clinical and neuroradiological findings are suggestive of neoplastic meningitis though without sufficient evidence of the primary tumor. And third, a spinal tap is performed for other reasons and malignant cells are an incidental finding.