Volume 43, Issue 3

Laboratory measurement values require interpretative assistance e.g. so-called guide limits (GL), as an interpretative aid. Legal and normative requirements for medical laboratories do not provide specific information for their implementation and verification. A German Society for Clinical Chemistry and Laboratory Medicine (DGKL) Working Group GL (WG-GL) has, therefore, developed recommendations to support medical laboratories in the management of GL. A specific objective was to create a framework that mainly takes into account those aspects that can be realistically implemented by routine laboratories and that should improve the management of GL of frequently requested quantitative measurement procedures in clinical chemistry. Thus, the focus of these recommendations is on the distinction between reference interval limits and clinical decision limits as well as the determination and verification of reference interval limits. Indirect approaches are highlighted, as they enable routine laboratories with a broad analytical spectrum but limited resources to evaluate or to establish reference limits.

Background The aim of this study was to validate a point-of-care C-reactive protein (CRP) test (QuikRead, wide-range [wr] CRP) against standard laboratory testing in neonates with suspected sepsis. Methods This was a single-centre prospective cohort study of neonates (n = 91). The main outcome measure was the paired evaluation of the wr-CRP point-of-care test and automated laboratory CRP tests in neonates with suspected sepsis. Results There were 126 measured CRP-sample pairs. The mean difference between the laboratory CRP and the wr-CRP point-of-care test values was 0.19 (95% confidence interval [CI]:‒1.0–0.65). Pearson’s correlation coefficient was 0.94. The area under the receiver operating characteristic (ROC) curve was 0.99 (95% CI: 0.98–1.00). At a QuikRead CRP cut-off of ≥6.2, the sensitivity and specificity were 77% and 100%, respectively. Conclusions Point-of-care wr-CRP testing can be used as a screening test in neonates with suspected sepsis. Rapid bed-side diagnostics and minimal blood volume requirements present an attractive alternative to common laboratory CRP testing.

Background Familial Mediterranean fever (FMF) is a disorder mainly present in the Mediterranean region, characterized by abdominal attacks that mimic acute peritonitis. Therefore, FMF might be confused with other conditions presenting with acute abdominal pain, particularly acute appendicitis (AA). We aimed to evaluate whether epithelial-derived neutrophil-activating peptide-78 (ENA-78) and fibrinogen levels and white blood cell (WBC) counts could be used as potential markers in the differential diagnosis of acute FMF attacks and AA. Methods The study involved three groups: patients with AA who underwent surgery (group 1, n = 30), patients with FMF attacks (group 2, n = 30), and patients with FMF who were attack-free (n = 30, controls), which included patients who were diagnosed as having FMF previously but had no attacks for a month. Results Significant differences were detected in the ENA-78 and fibrinogen levels between group 1 and group 2. No significant difference was found in the WBC count between group 1 and group 2. It was concluded that the WBC count was more sensitive (66%) for group 1, and fibrinogen showed higher sensitivity (86%) and specificity (96%) for group 2 compared with the other parameters. Conclusions We suggest that AA can be distinguished in patients with signs of peritonitis who were diagnosed as having FMF previously with the use of ENA-78 and fibrinogen levels; fibrinogen and ENA-78 might be helpful in discriminating between FMF attacks and AA.

Background When the dense fine speckled (DFS) pattern-antinuclear antibodies (ANA) are detected in the indirect immunofluorescence (IIF) assay, the presence of anti-dense fine speckles 70 (DFS70) antibodies has been suggested to facilitate the exclusion of ANA-associated rheumatic diseases (AARD). We evaluated the potential use of anti-DFS70 antibodies for verifying AARD in patients with a positive ANA result of the DFS pattern. Methods A total of 5509 patients who were requested ANA testing were included. The DFS pattern was confirmed using two IIF assays. Semiquantitative DFS70 ELISA (Euroimmun, Germany) was examined in samples with the DFS pattern. Results Among 639 ANA-positive patients, 19.6% displayed the DFS pattern. And 17.6% of patients with the DFS pattern were diagnosed with AARD. The low titer of 1:80 was more prevalent in the non-AARD group than in the AARD group (64.1% vs. 4.5%, p < 0.0001). Anti-DFS70 antibodies were positive in 60.0% of patients with the DFS pattern. The frequency of anti-DFS70 positivity was higher in the non-rheumatic disease (NRD) group (74.2%) than in the other rheumatic disease group (43.2%, p = 0.003) and the AARD group (45.5%, p = 0.019). Conclusions The DFS pattern is present in both AARD and non-AARD cases. In the DFS pattern, a low titer of 1:80 and isolated anti-DFS70 antibodies without AARD-associated antibodies represent a low likelihood of AARD. The presence of anti-DFS70 antibodies cannot exclude AARD and should be analyzed in combination with AARD-associated antibodies in the diagnostic algorithm.

Background The routine identification to the species level of Nocardia genus by conventional methods is a fastidious and time-consuming process owing to the limited biochemical reactivity of these microorganisms, often requiring 1 or more days to complete identification. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is a new technology for definitive and rapid species identification. Methods We evaluated the MALDI-TOF MS for the identification of 44 clinical isolates of Nocardia species in comparison to 16S ribosomal RNA (rRNA) gene sequencing. Nocardia isolates were identified by microbiological examination, phenotypical tests and MALDI-TOF MS and the results were compared by 16S rRNA gene sequencing. Results Of the 44 Nocardia strains, the identification of 28 isolates was determined with MALDI Biotyper database. According to this, 16 isolates (57.1%) of the strain log scores were ≥2. Two (7.1%) were identified to the species level (log scores of ≥2) as Nocardia otitidiscaviarum . The addition of a newly established Nocardia database (16 new Nocardia strains included to the original database) did significantly improve the scores. The results were 43 (97.7%) correct identification to the species level (log scores of ≥2). Conclusions This study showed that the identification of clinical Nocardia isolates by the Bruker MALDI Biotyper is highly reliable, whereas identification rates are generally lower than those for some Gram-negative bacteria and Gram-positive cocci. Based on our data, the identification rates can be improved by validated new database entries and the results can be confirmed with nucleic acid sequence analysis.

Background Immunoassays show variability in the detection of macroprolactin. The aim of this study was to detect the frequency of macroprolactinemia in hyperprolactinemic patients and the problems encountered in routine clinical practice. Methods The screening of macroprolactinemia was performed by precipitation with polyethylene glycol (PEG) in 900 patient samples with hyperprolactinemia over a period of approximately 6 months. Recovery values of less than 40% and greater than 60% were considered as macroprolactinemia and predominantly monomeric prolactin (PRL), respectively. Results A total of 900 (17.9%) of the 5007 PRL results were out of reference range. Thirty-one (3.4%) of the patients had less than 40% recovery after screening of all patients with hyperprolactinemia. However, the macroprolactin test was requested by clinics from only 171 patients and seven of these patients had less than 40% recovery. We also detected predominantly macroprolactin in 24 samples, overlooked in routine practice. The patients with PRL above 100 ng/mL had no macroprolactinemia. Conclusions The screening for macroprolactinemia of hyperprolactinemic patients who have <100 ng/mL and also with unexplained hyperprolactinemia should be the first approach before any further research or treatment is initiated. Thus, unnecessary test repetition, investigation and inappropriate treatment can be avoided. Each laboratory should inform clinicians about the frequency of macroprolactinemia.

Background To evaluate if procalcitonin (PCT) measurements made using the new point-of-care testing (POCT) ichroma™ are interchangeable with those made using Kryptor. Methods Serum samples (n = 117) were processed sequentially on Kryptor and ichroma™. Statistical analysis was performed using Passing-Bablok (PB) regression and the Bland-Altman (BA) test. Cohen’s kappa statistic was used to calculate the concordance at the clinically relevant cutoffs. Results PB regression did not show a significant deviation from linearity; proportional and constant differences were observed between ichroma™ and Kryptor. The 95% confidence interval (CI) of the mean bias percentage was very large, exceeding the maximum allowable total error (TE) (approximately 20%) and the clinical reference change value (about 60%). However, the concordance between methods at the clinically relevant cutoffs was strong, with the exception of the 0.25 ng/mL cutoff, which was moderate. Conclusions Our data suggest that ichroma™ is not interchangeable with Kryptor, so cannot be mixed; one must choose one instrument only and be consistent. However, while the strong concordance at the clinically relevant cutoffs allows us to consider ichroma™ a suitable option to Kryptor to support clinicians’ decision-making, nevertheless the moderate agreement at the 0.25 ng/mL cutoff recommends caution in interpreting the data around this cutoff.

Background Infections caused by carbapenem-resistant Enterobacterales (CREs) are an emerging problem associated with high rates of morbidity and mortality. CREs are divided into two categories (carbapenemase-producing [CP] CRE and non-CP CRE). The most prevalent carbapenemase produced by Enterobacterales is Klebsiella pneumoniae  carbapenemase (KPC) in Korea. Rapid identification of CREs is clinically important in infection control precaution. We compared the performance of two chromogenic media (chromID CARBA agar and CHROMagar KPC agar) for non-CP CREs or CP CREs with bla GES-5 , bla NDM-1 or bla VIM-2 in a Korean hospital. Methods The study was carried out during a 3-month period from April to June 2017 during the surveillance program for CRE colonization. Antimicrobial susceptibility testing (AST) and polymerase chain reaction (PCR) were performed at the Korean Centers for Disease Control and Prevention. Results A total of 45 rectal swabs from 42 hospitalized patients were examined. Sensitivity of both chromID CARBA and CHROMagar KPC were 100% for CP CREs; and 50% and 100% for non-CP CREs, respectively. Specificity of chromID CARBA and CHROMagar KPC were 89.2% and 70.3% for CP CRE, respectively; and 76.9% and 66.7% for non-CP CRE, respectively. Conclusions The CHROMagar KPC is useful to monitor non-CP and CP CREs. The chromID CARBA is efficient for rapid detection of CP CREs requiring high contact precaution.