SciCombinator

Discover the most talked about and latest scientific content & concepts.

Journal: Clinical chemistry and laboratory medicine

0

Introduction Recently, an expert consensus on optimal use of procalcitonin (PCT)-guided antibiotic stewardship was published focusing mainly on Europe and the United States. However, for Asia-Pacific countries, recommendations may need adaptation due to differences in types of infections, available resources and standard of clinical care. Methods Practical experience with PCT-guided antibiotic stewardship was discussed among experts from different countries, reflecting on the applicability of the proposed Berlin consensus algorithms for Asia-Pacific. Using a Delphi process, the group reached consensus on two PCT algorithms for the critically ill and the non-critically ill patient populations. Results The group agreed that the existing evidence for PCT-guided antibiotic stewardship in patients with acute respiratory infections and sepsis is generally valid also for Asia-Pacific countries, in regard to proposed PCT cut-offs, emphasis on diagnosis, prognosis and antibiotic stewardship, overruling criteria and inevitable adaptations to clinical settings. However, the group noted an insufficient database on patients with tropical diseases currently limiting the clinical utility in these patients. Also, due to lower resource availabilities, biomarker levels may be measured less frequently and only when changes in treatment are highly likely. Conclusions Use of PCT to guide antibiotic stewardship in conjunction with continuous education and regular feedback to all stakeholders has high potential to improve the utilization of antibiotic treatment also in Asia-Pacific countries. However, there is need for adaptations of existing algorithms due to differences in types of infections and routine clinical care. Further research is needed to understand the optimal use of PCT in patients with tropical diseases.

0

Background Biotin is currently a matter of concern for laboratories using biotin-streptavidin-based immunoassays. Biotin interferences have been reported for high-sensitive troponin T (hsTnT) and thyroid-stimulating hormone (TSH) assays. We aimed to evaluate the new generation of hsTnT and TSH electrochemiluminescent immunoassays announced to be less sensitive to biotin. Methods Firstly, we assessed the analytical performances of new generation assays (imprecision, bias, total error, limit of quantification) and compared previous and new generation assays in the absence of biotin. Secondly, we challenged both generations of assays with samples spiked with seven different biotin levels. The efficiency of new generation assays was also compared to the streptavidin beads treatment. Results New generation assays presented suitable analytical performances. Previous and new generations of hsTnT and TSH assays were commutable in the absence of biotin. In the presence of biotin, we confirmed that previous generation assays were affected by biotin concentration as low as 40.5 ng/mL and that new generation assays were not affected up to the announced tolerance threshold of 1200 ng/mL. After the streptavidin beads treatment, we observed a higher imprecision for both parameters and a constant 10% negative bias for TSH compared to new generation assays. Conclusions New generation of electrochemiluminescent immunoassays appears as a reliable systematic solution to prevent biotin interference for hsTnT and TSH testing.

0

Objectives Faecal immunochemical tests for haemoglobin (FIT) are becoming widely used in colorectal cancer (CRC) screening and assessment of symptomatic patients. Faecal haemoglobin concentration (f-Hb) thresholds are used to guide subsequent investigation. We established the distributions of f-Hb in a large screening population by sex, age, deprivation and geography. Methods Single estimates of f-Hb were documented for all individuals participating in the first 18 months of the Scottish Bowel Screening Programme (SBoSP). The distributions of f-Hb were generated for all participants, all men and women, and men and women by age quintile and deprivation quintile. Distributions were also generated by geographical region for all participants, men and women, and by deprivation. Comparisons of f-Hb distributions with those found in a pilot evaluation of FIT and three other countries were performed. Results f-Hb was documented for 887,248 screening participants, 422,385 men and 464,863 women. f-Hb varied by sex, age, deprivation quintile and geographical region. The f-Hb distributions by sex and age differed between the SBoSP and the pilot evaluation and the three other countries. Conclusions f-Hb is higher in men than in women and increases with age and deprivation in both sexes. f-Hb also varies by geographical region, independently of deprivation, and by country. The f-Hb distribution estimated by pilot evaluation may not represent the population distribution. Decision limits have advantages over reference intervals. Use of partitioned f-Hb thresholds for further investigation, based on the data generated, has advantages and disadvantages, as do risk scores based on a spectrum of influencing variables.

0

Objectives The quantitation of BCR-ABL1 mRNA is mandatory for chronic myeloid leukemia (CML) patients, and RT-qPCR is the most extensively used method in testing laboratories worldwide. Nevertheless, substantial variation in RT-qPCR results makes inter-laboratory comparability hard. To facilitate inter-laboratory comparative assessment, an international scale (IS) for BCR-ABL1 was proposed. Methods The laboratory-specific conversion factor (CF) to the IS can be derived from the World Health Organization (WHO) genetic reference panel; however, this material is limited to the manufacturers to produce and calibrate secondary reference reagents. Therefore, we developed secondary reference calibrators, as lyophilized cellular material, aligned to the IS. Our purpose was both to re-evaluate the CF in 18 previously harmonized laboratories and to propagate the IS to new laboratories. Results Our field trial including 30 laboratories across Latin America showed that, after correction of raw BCR-ABL1/ABL1 ratios using CF, the relative mean bias was significantly reduced. We also performed a follow-up of participating laboratories by annually revalidating the process; our results support the need for continuous revalidation of CFs. All participating laboratories also received a calibrator to determine the limit of quantification (LOQ); 90% of them could reproducibly detect BCR-ABL1, indicating that these laboratories can report a consistent deep molecular response. In addition, aiming to investigate the variability of BCR-ABL1 measurements across different RNA inputs, we calculated PCR efficiency for each individual assay by using different amounts of RNA. Conclusions In conclusion, for the first time in Latin America, we have successfully organized a harmonization platform for BCR-ABL1 measurement that could be of immediate clinical benefit for monitoring the molecular response of patients in low-resource regions.

0

Objectives Details of the biological variability of high-sensitivity C-reactive protein (hs-CRP), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and ST2 are currently lacking in patients with acute coronary syndrome (ACS) but are crucial knowledge when aiming to use these biomarkers for personalized risk prediction. In the current study, we report post-ACS kinetics and the variability of the hs-CRP, NT-proBNP and ST2. Methods BIOMArCS is a prospective, observational study with high frequency blood sampling during 1 year post-ACS. Using 1507 blood samples from 191 patients that remained free from adverse cardiac events, we investigated post-ACS kinetics of hs-CRP, NT-proBNP and ST2. Biological variability was studied using the samples collected between 6 and 12 months after the index ACS, when patients were considered to have stable coronary artery disease. Results On average, hs-CRP rose peaked at day 2 and rose well above the reference value. ST2 peaked immediately after the ACS but never rose above the reference value. NT-proBNP level rose on average during the first 2 days post-ACS and slowly declined afterwards. The within-subject variation and relative change value (RCV) of ST2 were relatively small (13.8%, RCV 39.7%), while hs-CRP (41.9%, lognormal RCV 206.1/-67.3%) and NT-proBNP (39.0%, lognormal RCV 185.2/-64.9%) showed a considerable variation. Conclusions Variability of hs-CRP and NT-proBNP within asymptomatic and clinically stable post-ACS patients is considerable. In contrast, within-patient variability of ST2 is low. Given the low within-subject variation, ST2 might be the most useful biomarker for personalizing risk prediction in stable post-ACS patients.

0

Objectives Mucopolysaccharidosis type I (MPS I) was added to our expanded screening panel in 2015. Since then, 127,869 newborns were screened by measuring α-L-iduronidase (IDUA) enzyme activity with liquid chromatography tandem mass spectrometry (LC-MS/MS). High false positives due to frequent pseudodeficiency alleles prompted us to develop a second-tier test to quantify glycosaminoglycan (GAG) levels in dried blood spot (DBS). Methods Heparan-sulfate (HS) and dermatan-sulfate (DS) were measured with LC-MS/MS after methanolysis. DBSs were incubated with methanolic-HCl 3 N at 65 °C for 45 min. Chromatographic separation used an amide column with a gradient of acetonitrile and water with 10 mM ammonium acetate in a 9-min run. The method was validated for specificity, linearity, lower limit of quantification (LOQ), accuracy and precision. Results Intra- and inter-day coefficients of variation were <15% for both metabolites. Reference values in 40 healthy newborns were: HS mean 1.0 mg/L, 0-3.2; DS mean 1.5 mg/L, 0.5-2.7). The two confirmed newborn MPS I patients had elevated HS (4.9-10.4 mg/L, n.v. <3.2) and DS (7.4-8.8 mg/L, n.v. <2.7). Since its introduction in February 2019, the second-tier test reduced the recall rate from 0.046% to 0.006%. Among 127,869 specimens screened, the incidence was 1:63,935 live births. Both patients started enzyme replacement therapy (ERT) within 15 days of birth and one of them received allogenic hematopoietic stem cell transplantation (HSCT) at ht age of 6 months. Conclusions GAGs in DBS increased the specificity of newborn screening for MPS I by reducing false-positives due to heterozygosity or pseudodeficiency. Early diagnosis and therapeutical approach has improved the outcome of our patients with MPS I.

0

Background Inorganic phosphate in blood is currently determined by the reaction with molybdate. This report aims at reviewing conditions underlying spuriously altered levels of circulating inorganic phosphate. Content A systematic search of the Excerpta Medica, the National Library Database and the Web of Science database was conducted without language restriction from the earliest publication date available through January 31, 2020. Summary For the analysis, 80 reports published in English (n = 77), French (n = 1), German (n = 1) and Spanish (n = 1) were retained. Well-documented pseudohyperphosphatemia was observed in individuals exposed to liposomal amphotericin, in patients affected by a gammopathy, in patients with hyperlipidemia and in patients with hyperbilirubinemia. An unexplained elevated inorganic phosphate level sometimes provided a clue to the diagnosis of a gammopathy. Well-documented cases of pseudohypophosphatemia were observed in patients on large amounts of intravenous mannitol. Finally, pseudohypophosphatemia was occasionally observed on treatment with liposomal amphotericin and in patients with a gammopathy. Outlook In order to avoid unnecessary testing and treatment, the phenomenon of spuriously altered inorganic phosphate should be recognized. An unexplained hyperphosphatemia may provide a clue to the diagnosis of a gammopathy or a severe hyperlipidemia.

0

Objectives Frozen and freeze-dried plasmas may be used for local prothrombin time system calibration, for direct international normalized ratio (INR) determination, and for quality assessment. The purpose of the present study was to evaluate the usefulness of INRs assigned with various types of thromboplastins to frozen and freeze-dried pooled plasmas obtained from patients treated with vitamin K antagonists. Methods INRs were calculated according to the international sensitivity index (ISI) model using various thromboplastins and instruments, i.e. International Standards for thromboplastin as well as six commercial reagents prepared from rabbit and bovine brain, and recombinant human tissue factor. The uncertainty of the INRs was assessed using the standard deviations of clotting times and ISI values. Commutability of the plasmas was assessed according to the approved Clinical and Laboratory Standards Institute (CLSI) Guideline EP30-A. Validation of a set of six frozen plasma pools for direct INR determination was performed according to the Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis (SSC/ISTH) guidelines. Results For all frozen and freeze-dried plasmas, the INRs calculated with bovine thromboplastin Thrombotest were lower than the INRs assigned with other thromboplastins. With a few exceptions, the frozen and freeze-dried pooled plasmas were commutable. When the set of six frozen plasma pools was used for local calibration, the analytical bias of the INR was less than ±10% for all commercial reagents except Thrombotest. Conclusions Processing of fresh plasmas to prepare pooled frozen plasmas and freeze-dried plasmas may lead to different INR assignments depending on the thromboplastin used. Despite minor INR differences, a set of six frozen plasma pools could be used for local calibration by direct INR determination.

0

Objectives Point-of-care (POC) analyzers are playing an increasingly important role in diabetes management but it is essential that we know the performance of these analyzers in order to make appropriate clinical decisions. Whilst there is a growing body of evidence around the more well-known analyzers, there are many ‘new kids on the block’ with new features, such as displaying the presence of potential Hb-variants, which do not yet have a proven track record. Methods The study is a comprehensive analytical and usability study of six POC analyzers for HbA1c using Clinical and Laboratory Standards Institute (CLSI) protocols, international quality targets and certified International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and National Glycohemoglobin Standardization Program (NGSP) Secondary Reference Measurement Procedures (SRMP). The study includes precision (EP-5 and EP-15), trueness (EP-9), linearity (EP-6), sample commutability (fresh, frozen and lyophilized), interference of Hb-variants (fresh and frozen samples). Results Only two of the six analyzers performed to acceptable levels over the range of performance criteria. Hb-variant interference, imprecision or variability between lot numbers are still poor in four of the analyzers. Conclusions This unique and comprehensive study shows that out of six POC analyzers studied only two (The Lab 001 and Cobas B101) met international quality criteria (IFCC and NGSP), two (A1Care and Innovastar) were borderline and two (QuikReadgo and Allegro) were unacceptable. It is essential that the scientific and clinical community are equipped with this knowledge in order to make sound decisions on the use of these analyzers.

0

Objectives Monoclonal immunoglobulins can cause interference in many laboratory analyses. During a 4 month period we observed seven patients with monoclonal disease and falsely extremely elevated 25-hydroxyvitamin D (25(OH)D) results above 160 ng/mL (>400 nmol/L) measured using an immunoassay from Abbott Diagnostics. Based on these findings, we studied the occurrence of falsely elevated 25(OH)D in samples with paraproteins and investigated possible mechanisms of the observed interference. Methods 25(OH)D was analyzed using the Architect i2000 platform from Abbott Diagnostics and a higher order method, liquid chromatography-mass spectrometry (LC-MS/MS), in serum samples from 50 patients with known monoclonal disease. Patients with falsely elevated 25(OH)D were included in further studies to elucidate the cause of interference. Spuriously elevated results were in addition analyzed on two alternative platforms (Siemens and Roche). Results Falsely elevated 25(OH)D levels were present in eight patients on the Abbott analyzer and one on the Siemens platform. Results from Roche were comparable with LC-MS/MS. Additional investigations excluded elevated concentrations of rheumatoid factor and heterophilic antibodies as the cause of interference in the Abbott assay. Conclusions Laboratories should be aware of the risk of falsely elevated 25(OH)D in samples run on the Architect analyzer from patients with monoclonal disease. Highly elevated vitamin D results should be diluted and if the dilution is non-linear, rerun by a different method, preferably LC-MS/MS. In patients with spuriously elevated 25(OH)D without known monoclonal disease, the laboratory should consider requesting protein electrophoresis to exclude paraprotein interference.