Volume 56, Issue 1

Neutrophil gelatinase-associated lipocalin (NGAL) is a promising diagnostic biomarker of early acute kidney injury. Increasing evidence suggests that NGAL may also be involved in inflammatory processes in cardiovascular disease. NGAL modulates the enzymatic activity of matrix metalloproteinase-9 (MMP-9), which is an important mediator of plaque instability in atherosclerosis. The complex formation between NGAL and MMP-9 therefore suggests that NGAL might play a role in progression of atherothrombotic disease. This review summarises current data on NGAL in atherosclerosis, acute myocardial infarction, and heart failure.

Periprosthetic joint infection (PJI) is a serious complication that may occur after native joint replacement leading to a severe health and economic burden. Currently, due to several confounding factors, PJI is difficult to diagnose. Today, a multidisciplinary approach is indispensable to correctly define a periprosthetic joint infection; indeed, tissue histology, microbiology cultures and clinical findings are used together to achieve this goal. Analysis of α-defensin is commonly used for PJI diagnosis, as it allows the rapid detection of α-defensin present in the synovial fluid following a microbial infection. Currently, a point-of-care testing (POCT) assay able to detect the presence of human α-defensins 1–3 in synovial fluid of patients is aimed directly at orthopedic surgeons. However, many orthopedic surgeons lack experience and training in quality laboratory practices, often failing to appreciate the significance of quality control and proper documentation when using POCT assays. To guarantee the highest quality diagnostic services, the α-defensin test should be used together with other biochemical and microbiological criteria commonly used for PJI diagnosis. Additionally, the close cooperation and communication between laboratory, pathologists and physicians is of fundamental importance in the correct diagnosis of PJI.

Primary biliary cholangitis (PBC), also known as primary biliary cirrhosis, is an autoimmune disease of the liver characterized by anti-mitochondrial antibodies (AMA) in 90%–95% of patients. The aim of this study was to evaluate the diagnostic value of several serum biomarkers in patients with PBC but negative for AMA. Some antinuclear antibodies (ANA) pattern, detected by indirect immunofluorescence (IIF), such as multiple nuclear dot (MND) and rim-like patterns are well-known to be specific for PBC. The corresponding nuclear antigens are the components of the nuclear pore complex (Gp210 for rim-like pattern) and Sp100, PML proteins (for MND pattern) detectable by immunoblotting and ELISA methods. More recently, new biomarkers have been evaluated in order to improve the diagnostic sensitivity, such as kelch-like 12 (KLHL12) and hexokinase-1. Considering these different serum biomarkers, studies evaluating their diagnostic role in AMA-negative PBC patients compared to AMA-positive ones and controls were included in this review. Pooled sensitivity and specificity were 37% and 85%, respectively. The overall PPV and NPV mean values were 45% and 83%. Even if all biomarkers are very specific for PBC, the overall sensitivity was poor and therefore is necessary to identify a marker with a greater sensitivity for PBC in AMA-negative patients.

The measurement of the active hormone of B-type natriuretic peptide (BNP) system actually has several analytical limitations and difficulties in clinical interpretations compared to that of inactive peptide N-terminal proBNP (NT-proBNP) because of the different biochemical and pathophysiological characteristics of two peptides and quality specifications of commercial immunoassay methods used for their measurement. Because of the better analytical characteristics of NT-proBNP immunoassays and the easier pathophysiological and clinical interpretations of variations of NT-proBNP levels in patients with heart failure (HF), some authors claimed to measure the inactive peptide NT-proBNP instead of the active hormone BNP for management of HF patients. The measurement of the active peptide hormone BNP gives different, but complementary, pathophysiological and clinical information compared to inactive NT-proBNP. In particular, the setup of new more sensitive and specific assays for the biologically active peptide BNP 1-32 should give better accurate information on circulating natriuretic activity. In conclusion, at present time, clinicians should accurately consider both the clinical setting of patients and the analytical characteristics of BNP and NT-proBNP immunoassays in order to correctly interpret the variations of natriuretic peptides measured by commercially available laboratory methods, especially in patients treated with the new drug class of angiotensin receptor-neprilysin inhibitors.

Background: The development of technologies that detect monogenic diseases in embryonic and fetal samples are opening novel diagnostic possibilities for preimplantation genetic diagnosis (PGD) and prenatal diagnosis (PND) thereby changing laboratory practice. Molecular diagnostic laboratories use different workflows for PND depending on the disease, type of biological sample, the presence of one or more known mutations, and the availability of the proband. Paternity verification and contamination analysis are also performed. The aim of this study was to test the efficacy of a single workflow designed to optimize the molecular diagnosis of monogenic disease in families at-risk of transmitting a genetic alteration. Methods: We used this strategy, which we designated “SEeMORE strategy” ( S ingle-tube E l e ctrophoresis analysis-based genotyping to detect MO nogenic diseases R apidly and E ffectively from conception to birth). It consists of a multiplex PCR that simultaneously carries out linkage analysis, direct analysis, maternal contamination and parenthood testing. We analyzed samples from previously diagnosed families for PND (cystic fibrosis or Duchenne muscular dystrophy) without, however, knowing the results. Results: The results obtained with the SEeMORE strategy concurred with those obtained with traditional PND. In addition, this strategy has several advantages: (i) use of one or a few cells; (ii) reduction of the procedure to 1 day; and (iii) a reduction of at least 2–3-fold of the analytic cost. Conclusions: The SEeMORE strategy is effective for the molecular diagnosis of monogenic diseases, irrespective of the amount of starting material and of the disease mutation, and can be used for PND and PGD.

Background : Serum calcium level is an important clinical index that reflects pathophysiological states. However, detection accuracy in laboratory tests is not ideal; as such, a high accuracy method is needed. Methods: We developed a reference method for measuring serum calcium levels by isotope dilution inductively coupled plasma mass spectrometry (ID ICP-MS), using 42 Ca as the enriched isotope. Serum was digested with 69% ultrapure nitric acid and diluted to a suitable concentration. The 44 Ca/ 42 Ca ratio was detected in H 2 mode; spike concentration was calibrated by reverse IDMS using standard reference material (SRM) 3109a, and sample concentration was measured by a bracketing procedure. We compared the performance of ID ICP-MS with those of three other reference methods in China using the same serum and aqueous samples. Results: The relative expanded uncertainty of the sample concentration was 0.414% (k=2). The range of repeatability (within-run imprecision), intermediate imprecision (between-run imprecision), and intra-laboratory imprecision were 0.12%–0.19%, 0.07%–0.09%, and 0.16%–0.17%, respectively, for two of the serum samples. SRM909bI, SRM909bII, SRM909c, and GBW09152 were found to be within the certified value interval, with mean relative bias values of 0.29%, −0.02%, 0.10%, and −0.19%, respectively. The range of recovery was 99.87%–100.37%. Results obtained by ID ICP-MS showed a better accuracy than and were highly correlated with those of other reference methods. Conclusions: ID ICP-MS is a simple and accurate candidate reference method for serum calcium measurement and can be used to establish and improve serum calcium reference system in China.

Background: We recently observed that exposure to dry ice lowered sample pH and increased clotting times in lupus anticoagulant analyses, and that such changes could be prevented by placing samples at −80°C after dry ice exposure. In the current study, we sought to evaluate the effects of dry ice exposure on pH and various commonly used coagulation analyses. Methods: Citrated plasma from 30 healthy blood donors was allocated to four preanalytical regimes: (1) immediate analysis of fresh plasma or (2) storage at −20°C; (3) storage at −20°C followed by dry ice exposure for 24 h or (4) storage at −20°C followed by dry ice exposure for 24 h and storage at −80°C for 24 h before analysis. Analyses of pH, prothrombin time international normalized ratio (PT-INR), activated partial thromboplastin time (APTT), antithrombin, fibrinogen, protein C and protein S was performed. Results: Samples exposed to dry ice had significantly lower pH, prolonged clotting times in PT-INR, APTT and fibrinogen analyses as well as lower levels of protein C, than samples not exposed to dry ice. These changes in coagulation analyses were not present if samples were stored at −80°C for 24 h after dry ice exposure. Antithrombin and protein S were not significantly affected by dry ice exposure. Conclusions: Dry ice exposure lowered sample pH and affected various coagulation analyses. These effects were avoided by storing samples at −80°C for 24 h after dry ice exposure.

Background: Placental protein-13 (PP13) is involved in placental invasion and has been suggested as a maternal serum marker of preeclampsia (PE) development. However, the discriminatory ability of PP13 in first trimester has not been completely clarified. Methods: PP13 was measured in first trimester (week 10 +3 –13 +6 ) maternal serum from 120 PE pregnancies and 267 control pregnancies and was correlated with clinical parameters. The population screening performance of PP13 in combination with the PE markers pregnancy associated plasma protein A (PAPPA) and free leptin index (fLI) was assessed by Monte Carlo simulation. Results: In severe PE (including HELLP) cases (n=26) the median PP13 concentration was 35.8 pg/mL (range: 17.8–85.5 pg/mL) and in PE pregnancies (n=10) with birth prior to week 34, the median PP13 concentration was 30.6 pg/mL (13.1–50.1 pg/mL), compared to controls with a median of 54.8 pg/mL (range: 15.4–142.6 pg/mL) (p<0.04). The population screening detection rate (DR) for a false-positive rate of 10% for severe PE and HELLP was 26% for PP13, 28% for PP13+PAPP-A, 33% for PP13+fLI, and 40% for PP13+PAPP-A+fLI. Conclusions: PP13 is a marker of severe PE and HELLP syndrome. The screening performance of PP13 can be markedly improved by combining it with fLI and PAPP-A.

Background: Soluble CD89 (sCD89)-IgA complex plays a key role in the pathogenesis of IgA nephropathy (IgAN). However, there is a lack of evidence supporting this complex as a good biomarker for disease progression. This study aimed to evaluate the usefulness of sCD89-IgA complex for risk stratification of IgAN. Methods: A total of 326 patients with biopsy-proven IgAN were included. sCD89-IgA complex was measured by sandwich-enzyme-linked immunosorbent assay. The study endpoints were a 30% decline in estimated glomerular filtration rate (eGFR). Results: sCD89-IgA complex levels were inversely and weakly associated with eGFR at the time of biopsy (r=−0.12, p=0.03). However, the significance between the two factors was lost in the multivariate linear regression after adjustment of clinical factors (β=0.35, p=0.75). In a multivariate Cox model, the highest (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.35–1.61; p=0.45) and middle (HR, 0.93; 95% CI, 0.46–1.89; p=0.84) tertiles of sCD89-IgA complex levels were not associated with an increased risk of developing a 30% decrease in eGFR. Furthermore, the decline rates in eGFR did not differ between groups and C-statistics revealed that the sCD89-IgA complex were not superior to clinical factors in predicting disease progression. Conclusions: This study found no association between sCD89-IgA complex levels and disease progression in IgAN. Although sCD89 can contribute to the formation of immune complexes, our findings suggest that the sCD89-IgA level is not a good predictor of adverse outcomes and has limited clinical utility as a biomarker for risk stratification in IgAN.

Background: Antibodies directed against dsDNA are a highly specific diagnostic marker for the presence of systemic lupus erythematosus and of particular importance in its diagnosis. To assess anti-dsDNA antibodies, the Crithidia luciliae -based indirect immunofluorescence test (CLIFT) is one of the assays considered to be the best choice. To overcome the drawback of subjective result interpretation that inheres indirect immunofluorescence assays in general, automated systems have been introduced into the market during the last years. Among these systems is the EUROPattern Suite, an advanced automated fluorescence microscope equipped with different software packages, capable of automated pattern interpretation and result suggestion for ANA, ANCA and CLIFT analysis. Methods: We analyzed the performance of the EUROPattern Suite with its automated fluorescence interpretation for CLIFT in a routine setting, reflecting the everyday life of a diagnostic laboratory. Three hundred and twelve consecutive samples were collected, sent to the Central Diagnostic Laboratory of the Maastricht University Medical Centre with a request for anti-dsDNA analysis over a period of 7 months. Results: Agreement between EUROPattern assay analysis and the visual read was 93.3%. Sensitivity and specificity were 94.1% and 93.2%, respectively. The EUROPattern Suite performed reliably and greatly supported result interpretation. Conclusions: Automated image acquisition is readily performed and automated image classification gives a reliable recommendation for assay evaluation to the operator. The EUROPattern Suite optimizes workflow and contributes to standardization between different operators or laboratories.

Background: The Sysmex DI-60 system (DI-60, Sysmex, Kobe, Japan) is a new automated digital cell imaging analyzer. We explored the performance of DI-60 in comparison with Sysmex XN analyzer (XN, Sysmex) and manual count. Methods: In a total of 276 samples (176 abnormal and 100 normal samples), white blood cell (WBC) differentials, red blood cell (RBC) classification and platelet (PLT) estimation by DI-60 were compared with the results by XN and/or manual count. RBC morphology between pre-classification and verification was compared according to the ICSH grading criteria. The manual count was performed according to the Clinical and Laboratory Standards Institute guidelines (H20-A2). Results: The overall concordance between DI-60 and manual count for WBCs was 86.0%. The agreement between DI-60 pre-classification and verification was excellent (weighted κ=0.963) for WBC five-part differentials. The correlation with manual count was very strong for neutrophils (r=0.955), lymphocytes (r=0.871), immature granulocytes (r=0.820), and blasts (r=0.879). RBC grading showed notable differences between DI-60 and manual counting on the basis of the ICSH grading criteria. Platelet count by DI-60 highly correlated with that by XN (r=0.945). However, DI-60 underestimated platelet counts in samples with marked thrombocytosis. Conclusions: The performance of DI-60 for WBC differential, RBC classification, and platelet estimation seems to be acceptable even in abnormal samples with improvement after verification. DI-60 would help optimize the workflow in hematology laboratory with reduced manual workload.

Background: Urinary steroid profiling (USP) is a powerful diagnostic tool to asses disorders of steroidogenesis. Pre-analytical factors such as age, sex and use of oral contraceptive pills (OCP) may affect steroid hormone synthesis and metabolism. In general, USP reference intervals are not adjusted for these variables. In this study we aimed to establish such reference intervals using a newly-developed and validated gas chromatography with tandem mass spectrometry detection method (GC-MS/MS). Methods: Two hundred and forty healthy subjects aged 20–79 years, stratified into six consecutive decade groups each containing 20 males and 20 females, were included. None of the subjects used medications. In addition, 40 women aged 20–39 years using OCP were selected. A GC-MS/MS assay, using hydrolysis, solid phase extraction and double derivatization, was extensively validated and applied for determining USP reference intervals. Results: Androgen metabolite excretion declined with age in both men and women. Cortisol metabolite excretion remained constant during life in both sexes but increased in women 70–79 years of age. Progesterone metabolite excretion peaked in 30–39-year-old women and declined afterwards. Women using OCP had lower excretions of androgen metabolites, progesterone metabolites and cortisol metabolites. Method validation results met prerequisites and revealed the robustness of the GC-MS/MS method. Conclusions: We developed a new GC-MS/MS method for USP which is applicable for high throughput analysis. Widely applicable age and sex specific reference intervals for 33 metabolites and their diagnostic ratios have been defined. In addition to age and gender, USP reference intervals should be adjusted for OCP use.

Background: Vasopressin and adrenomedullin and their stable by-products copeptin and midregional part of proadrenomedullin (MR-proADM) are promising biomarkers for the development of preeclampsia. However, clinical use is hampered by the lack of trimester-specific reference intervals. We therefore estimated reference intervals for copeptin and MR-proADM in disease-free Dutch women throughout pregnancy. Methods: Apparently healthy low risk pregnant women were recruited. Exclusion criteria included current or past history of endocrine disease, multiple pregnancy, use of medication known to influence thyroid function and current pregnancy as a result of hormonal stimulation. Women who miscarried, developed hyperemesis gravidarum, hypertension, pre-eclampsia, hemolysis elevated liver enzymes and low platelets, diabetes or other disease, delivered prematurely or had a small for gestational age neonate were excluded from analyses. Blood samples were collected at 9–13 weeks (n=98), 27–29 weeks (n=94) and 36–39 weeks (n=91) of gestation and at 4–13 weeks post-partum (PP) (n=89). Sixty-two women had complete data during pregnancy and PP. All analyses were performed on a Kryptor compact plus. Results: Copeptin increases during pregnancy, but 97.5th percentiles remain below the non-pregnant upper reference limit (URL) provided by the manufacturer. MR-proADM concentrations increase as well during pregnancy. In trimesters 2 and 3 the 97.5th percentiles are over three times the non-pregnant URL provided by the manufacturer. Conclusions: Trimester- and assay-specific reference intervals for copeptin and MR-proADM should be used. In addition, consecutive measurements and the time frame between measurements should be considered as the differences seen with or in advance of preeclampsia can be expected to be relatively small compared to the reference intervals.

Background: Glycated Albumin (GA) has been proposed as a short-term indicator of glycemic homeostasis. The aim of this study is to describe the distribution of GA in a large sample of blood donors from Italy to evaluate whether demographic features, namely age and sex, could influence GA levels and define specific reference limits. Methods: The study included 1334 Italian blood donors. GA was measured using an enzymatic method (quantILab Glycated Albumin, IL Werfen, Germany). The upper reference limit (URL) was calculated using the non-parametric percentile method. Results: A modest, although significant, increase of GA was observed in relation to age (p<0.001), especially in males, where the differences were more pronounced (p<0.001 in males, p=0.003 in females). Slight differences were documented based on sex (12% [11.3–12.8] in males; 12.2% [11.4–13.1] in females; p=0.01). After excluding individuals with fasting plasma glucose ≥7 mmol/L, the calculated GA URL was 14.5% (95% CI: 14.3–14.7). Subjects with GA>14.5% presented a mean age of 48.4±12.2 years, 66.7% were males and the mean glucose was 6.88±2.5 mmol/L. Conclusions: GA in Caucasians shows a similar increasing trend at older ages documented in other ethnicities. The definition of the URL in this population could be useful for both clinical studies, which will clarify the role of GA for diagnosing and monitoring diabetes, and will encourage the introduction of GA in clinical practice.

Background: Calgranulin C (S100A12) is an emerging marker of inflammation. It is exclusively released by activated neutrophils which makes this marker potentially more specific for inflammatory bowel disease (IBD) compared to established stool markers including calprotectin and lactoferrin. We aimed to establish a reference value for S100A12 in healthy children and investigated whether S100A12 levels can discriminate children with IBD from healthy controls. Methods: In a prospective community-based reference interval study we collected 122 stool samples from healthy children aged 5–19 years. Additionally, feces samples of 41 children with suspected IBD (who were later confirmed by endoscopy to have IBD) were collected. Levels of S100A12 were measured with a sandwich enzyme-linked immunosorbent assay (ELISA) (Inflamark ® ). The limit of detection was 0.22 μg/g. Results: The upper reference limit in healthy children was 0.75 μg/g (90% confidence interval: 0.30–1.40). Median S100A12 levels were significantly higher in patients with IBD (8.00 μg/g [interquartile range (IQR) 2.5–11.6] compared to healthy controls [0.22 μg/g (IQR<0.22); p<0.001]). The best cutoff point based on receiver operating characteristic curve was 0.33 μg/g (sensitivity 93%; specificity 97%). Conclusions: Children and teenagers with newly diagnosed IBD have significantly higher S100A12 results compared to healthy individuals. We demonstrate that fecal S100A12 shows diagnostic promise under ideal testing conditions. Future studies need to address whether S100A12 can discriminate children with IBD from non-organic disease in a prospective cohort with chronic gastrointestinal complaints, and how S100A12 performs in comparison with established stool markers.

Background: Decreased concentrations of pro-atrial-derived natriuretic peptides (proABP) in plasma have been associated with obesity and suggested as a predictor of type 2 diabetes. However, assays for measuring proANP are generally aimed to quantitate higher concentrations of proANP associated with cardiac disease. Therefore, we aimed to measure plasma proANP concentrations in a non-obese Scandinavian reference material and evaluate potential associations of plasma proANP with body mass index (BMI) and plasma glucose, respectively. Methods: We report an optimized processing-independent assay (PIA) for proANP in the lower concentration range. The assay was optimized by raising the amount of radioactive tracer and modifying the mixing ratio of resuspended plasma and buffer. Blood samples from a Scandinavian plasma cohort of 693 healthy subjects were then analyzed and age and gender-specific reference intervals were determined. Results: Simple linear regression analyses of proANP and both BMI and plasma glucose in fasting subjects displayed insignificant associations. Multiple regression analyses supported these findings. However, a higher median plasma concentration of proANP was noted among women <50 years compared to men, whereas no gender-specific differences were seen in other age groups. Conclusions: Our results show that in a healthy non-obese population, BMI and plasma glucose in fasting subjects do not affect plasma proANP concentrations. Our method should be considered for future studies on low proANP concentration studies, e.g. in obesity and diabetes.

Background: Identification of cancer biomarkers to allow early diagnosis is an urgent need for many types of tumors, whose prognosis strongly depends on the stage of the disease. Canine olfactory testing for detecting cancer is an emerging field of investigation. As an alternative, here we propose to use GC-Olfactometry (GC/O), which enables the speeding up of targeted biomarker identification and analysis. A pilot study was conducted in order to determine odor-active compounds in urine that discriminate patients with gastrointestinal cancers from control samples (healthy people). Methods: Headspace solid phase microextraction (HS-SPME)-GC/MS and GC-olfactometry (GC/O) analysis were performed on urine samples obtained from gastrointestinal cancer patients and healthy controls. Results: In total, 91 key odor-active compounds were found in the urine samples. Although no odor-active biomarkers present were found in cancer carrier’s urine, significant differences were discovered in the odor activities of 11 compounds in the urine of healthy and diseased people. Seven of above mentioned compounds were identified: thiophene, 2-methoxythiophene, dimethyl disulphide, 3-methyl-2-pentanone, 4-(or 5-)methyl-3-hexanone, 4-ethyl guaiacol and phenylacetic acid. The other four compounds remained unknown. Conclusions: GC/O has a big potential to identify compounds not detectable using untargeted GC/MS approach. This paves the way for further research aimed at improving and validating the performance of this technique so that the identified cancer-associated compounds may be introduced as biomarkers in clinical practice to support early cancer diagnosis.

Background: Neutrophil gelatinase associated lipocalin (NGAL) is expressed in atherosclerotic lesions and was recently implicated in the pathogenesis of cardiovascular pathologies. Statins are known to exert stabilizing effects on atherosclerotic plaque. The aims of our study were (1) to investigate the association of serum NGAL and metalloproteinase (MMP)-9/NGAL complex with the vulnerability of the atherosclerotic plaque, and (2) to reveal the effects of statin treatment on circulating NGAL and MMP-9/NGAL levels in patients with carotid artery stenosis. Methods: We examined the levels of NGAL and MMP-9/NGAL in blood samples from 136 patients with carotid artery stenosis by specific enzyme-linked immunosorbent assays. Results: Patients with vulnerable plaques, as determined by ultrasound (plaques with decreased echogenicity) and histological analysis (type VI according to the classification of American Heart Association [AHA]), displayed the highest levels of NGAL (both p<0.0001) and MMP-9/NGAL complex (p=0.0004 and p=0.004, respectively). Moreover, patients with symptomatic carotid atherosclerosis had significantly higher NGAL levels compared to asymptomatic patients (p=0.0007). The statin-treated group (n=108) demonstrated lower NGAL (73.9 vs. 128.0 μg/L, p<0.0001) and MMP-9/NGAL (28.9 vs. 40.6 μg/L, p=0.046) as compared to the non-statin group (n=28). Furthermore, in multivariate regression analysis NGAL, but not MMP-9/NGAL levels, were independently associated with symptomatic carotid artery stenosis. In addition, statin treatment was independently associated with lower NGAL levels. Conclusions: Circulating NGAL and MMP-9/NGAL are associated with plaque vulnerability in patients with carotid artery stenosis. Statin treatment could contribute to plaque stabilization by reducing circulating NGAL and MMP-9/NGAL levels.

Background: This study was aimed to evaluate the analytical performance of the novel chemiluminescent and fully-automated Beckman Coulter Access hsTnI high-sensitivity immunoassay for measurement of cardiac troponin I (cTnI). Methods: The study, using lithium heparin samples, included assessment of limit of blank (LOB), limit of detection (LOD), functional sensitivity, linearity, imprecision (within run, between-run and total), calculation of 99th percentile upper reference limit (URL) in 175 healthy blood donors (mean age, 36±12 years; 47% women) and comparison with two other commercial cTnI immunoassays. Results: The LOB, LOD and functional sensitivity of Access hsTnI were 0.14, 0.34 and 1.35 ng/L, respectively. The within-run, between-run and total imprecision was 2.2%–2.9%, 4.6%–5.4%, and 5.4%–6.1%, respectively. The linearity was excellent in the range of cTnI values between 0.95 and 4195 ng/L (r=1.00). The 99th percentile URL was 15.8 ng/L. Measurable cTnI values were found in 173/175 healthy subjects (98.9%). Good agreement of cTnI values was found with AccuTnI+3 (r=0.97; mean bias, −9.3%), whereas less satisfactory agreement was found with Siemens Dimension Vista cTnI (r=0.95; mean bias, −55%). Conclusions: The results of our evaluation of the Beckman Coulter Access hsTnI indicate that the analytical performance of this fully-automated immunoassay is excellent.

Background: Procalcitonin (PCT) is a recognized marker of sepsis, and its use is expanding to antibiotic stewardship. The aim of this study was the evaluation of two methods: Diazyme PCT on Roche Cobas c702 (PCT-D) and BRAHMS PCT on Roche Cobas e602 analyzers (PCT-BR) in comparison with BRAHMS PCT-sensitive Kryptor (PCT-BK). Methods: Imprecision was assessed at six critical concentrations following the CLSI EP5-A3; limits of detection (LoDs) were checked according to CLSI EP17-A2; linearity was tested, and method comparison was performed on 239 serum samples. Results: Overall CVs ranged from 12.58% to 5.97% for PCT-D, from 3.94% to 1.70% for PCT-BR and from 6.57% to 1.90% for PCT-BK. LoDs were 0.143 μg/L, 0.014 μg/L, 0.040 μg/L for PCT-D, PCT-BR and PCT-BK, respectively. The functional assay sensitivity was 0.24 μg/L for PCT-D, 0.045 μg/L for PCT-BK and <0.035 μg/L for PCT-BR. PCT-BR was linear up to 68.7 μg/L, PCT-BK up to 43 μg/L and PCT-D up to 27.2 μg/L. Method comparison: PCT-D=0.6543 PCT-BK+0.014, r=0.8463 (but 0.44 if calculated on 0–5 μg/L range); PCT-BR=0.9125 PCT-BK+0.021, r=0.9917. Cohen’s κ ranged from 45.2% at 0.25 μg/L to 57.0% at 2.00 μg/L between PCT-D and PCT-BK, whereas it ranged from 89% to 81.3% between PCT-BR and PCT-BK. Conclusions: The PCT-D performances were significantly different from those of PCT-BR and PCT-BK regarding sensitivity, precision, linearity and agreement at clinical cutoffs. For some patients with serial testing, significantly deviating results were obtained compared to reference. In contrast to Roche PCT assay, it does not seem feasible to use BRAHMS PCT cutoffs for the Diazyme test.

Background: Several trials found procalcitonin (PCT) helpful for guiding antibiotic treatment in patients with lower respiratory tract infections and sepsis. We aimed to perform an individual patient data meta-analysis on the effects of PCT guided antibiotic therapy in upper respiratory tract infections (URTI). Methods: A comprehensive search of the literature was conducted using PubMed (MEDLINE) and Cochrane Library to identify relevant studies published until September 2016. We reanalysed individual data of adult URTI patients with a clinical diagnosis of URTI. Data of two trials were used based on PRISMA-IPD guidelines. Safety outcomes were (1) treatment failure defined as death, hospitalization, ARI-specific complications, recurrent or worsening infection at 28 days follow-up; and (2) restricted activity within a 14-day follow-up. Secondary endpoints were initiation of antibiotic therapy, and total days of antibiotic exposure. Results: In total, 644 patients with a follow up of 28 days had a final diagnosis of URTI and were thus included in this analysis. There was no difference in treatment failure (33.1% vs. 34.0%, OR 1.0, 95% CI 0.7–1.4; p=0.896) and days with restricted activity between groups (8.0 vs. 8.0 days, regression coefficient 0.2 (95% CI –0.4 to 0.9), p=0.465). However, PCT guided antibiotic therapy resulted in lower antibiotic prescription (17.8% vs. 51.0%, OR 0.2, 95% CI 0.1–0.3; p<0.001) and in a 2.4 day (95% CI –2.9 to –1.9; p<0.001) shorter antibiotic exposure compared to control patients. Conclusions: PCT guided antibiotic therapy in the primary care setting was associated with reduced antibiotic exposure in URTI patients without compromising outcomes.