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  • Zhou, Q., et al. (författare)
  • Alpha-1-acid glycoprotein 1 is upregulated in pancreatic ductal adenocarcinoma and confers a poor prognosis
  • 2019
  • Ingår i: Translational Research. - Elsevier. - 1931-5244. ; 212, s. 67-79
  • Tidskriftsartikel (refereegranskat)abstract
    • Pancreatic cancer is an aggressive malignancy that carries a high mortality rate. A major contributor to the poor outcome is the lack of effective molecular markers. The purpose of this study was to develop protein markers for improved prognostication and noninvasive diagnosis. A mass spectrometry (MS)-based discovery approach was applied to pancreatic cancer tissues and healthy pancreas. In the verification phase, extracellular proteins with differential expression were further quantified in targeted mode using parallel reaction monitoring (PRM). Next, a tissue microarray (TMA) cohort including 140 pancreatic cancer resection specimens was constructed, in order to validate protein expression status and investigate potential prognostic implications. The levels of protein candidates were finally assessed in a prospective series of 110 serum samples in an accredited clinical laboratory using the automated Cobas system. Protein sequencing with nanoliquid chromatography tandem MS (nano-LC-MS/MS) and targeted PRM identified alpha-1-acid glycoprotein 1 (AGP1) as an upregulated protein in pancreatic cancer tissue. Using TMA and immunohistochemistry, AGP1 expression was significantly associated with shorter overall survival (HR = 2.22; 95% CI 1.30–3.79, P = 0.004). Multivariable analysis confirmed the results (HR = 1.87; 95% CI 1.08–3.24, P = 0.026). Circulating levels of AGP1 yielded an area under the curve (AUC) of 0.837 for the discrimination of resectable pancreatic cancer from healthy controls. Combining AGP1 with CA 19-9 enhanced the diagnostic performance, with an AUC of 0.963. This study suggests that AGP1 is a novel prognostic biomarker in pancreatic cancer tissue. Serum AGP1 levels may be useful as part of a biomarker panel for early detection of pancreatic cancer but further studies are needed.
  • Ziegler, Ingrid, 1976-, et al. (författare)
  • Evaluation of a Commercial Multiplex PCR Assay for Detection of Pathogen DNA in Blood from Patients with Suspected Sepsis
  • 2016
  • Ingår i: PLoS ONE. - San Francisco, USA : Public Library of Science. - 1932-6203. ; 11:12
  • Tidskriftsartikel (refereegranskat)abstract
    • The Magicplex Sepsis Real-time Test (MST) is a commercial multiplex PCR that can detect more than 90 different pathogens in blood, with an analysis time of six hours. The aim of the present study was to evaluate this method for the detection of bloodstream infection (BSI). An EDTA whole blood sample for MST was collected together with blood cultures (BC) from patients with suspected sepsis at the Emergency Department of a university hospital. Among 696 study patients, 322 (46%) patients were positive with at least one method; 128 (18%) were BC positive and 268 (38%) were MST positive. Considering BC to be the gold standard, MST had an overall sensitivity of 47%, specificity of 66%, positive predictive value (PPV) of 23%, and a negative predictive value of 87%. Among the MST positive samples with a negative BC, coagulase-negative staphylococci (CoNS) and species that rarely cause community-acquired BSI were frequently noted. However, the quantification cycle (Cq) values of the MST+/BC- results were often high. We thus hypothesized that the performance of the MST test could be improved if the Cq cut-off level was adjusted downwards. With a lower Cq cut-off value, i.e. 6.0 for Staphylococcus species and 9.0 for all other species, the number of MST positive cases decreased to 83 (12%) and the overall sensitivity decreased to 38%. However, the PPV increased to 59% and the specificity increased to 96%, as many MST positive results for CoNS and bacteria that rarely cause community-acquired BSI turned MST negative. In conclusion, our study shows that with a lower Cq cut-off value, the MST will detect less contaminants and findings with unclear relevance, but to the cost of a lower sensitivity. Consequently, we consider that a positive MST results with a Cq value above the adjusted cut-off should be interpreted with caution, as the result might be clinically irrelevant. In a correspondent way, quantitative results could probably be useful in the interpretation of positive results from other molecular assays for the detection of BSI.
  • Åstrand, Ramona, et al. (författare)
  • Comparison between capillary, venous and arterial levels of protein S100B in patients with severe brain pathology
  • 2012
  • Ingår i: Clinical Chemistry and Laboratory Medicine. - De Gruyter. - 1434-6621. ; 50:6, s. 1055-1061
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Protein S100B is soon in clinical use as a sensitive marker after mild traumatic head injury in adults. Initial studies of S100B in pediatric head injury have shown promising results. Venous sampling can be challenging in children and capillary samples are often a preferred option. The aim of the study was to investigate the relation between capillary, venous and arterial measurements of protein S100B, primarily by determining whether capillary S100B differ from venous and if capillary S100B can predict venous S100B levels, and secondarily, if arterial S100B samples can substitute venous samples in severely brain-injured patients. Methods: Venous, arterial and capillary blood samples for S100B were collected simultaneously once a day for a maximum of 6 days. Patients were >= 18 years old and admitted to neurointensive care due to severe brain pathology. Results: Capillary S100B samples were on average 0.08 mu g/L higher than venous S100B samples. Prediction of venous concentration from capillary samples yielded a prediction error of 0.07 mu g/L. The mean difference between venous and arterial samples was 0.01 mu g/L. The mean prediction error was 0.03 mu g/L. Conclusions: Capillary and venous serum S100B are not interchangeable, and should be considered as two separate, although related, variables. Arterial measurements of S100B can successfully predict the corresponding venous concentration.
  • Åstrand, Ramona, et al. (författare)
  • Reference values for venous and capillary S100B in children
  • 2011
  • Ingår i: Clinica Chimica Acta. - Elsevier. - 0009-8981. ; 412:23-24, s. 2190-2193
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract in Undetermined Background: The current management guidelines for pediatric mild head injury (MHI) liberally recommend computed tomography (CT) and frequent admission. Serum protein S100B, currently used in management of adult head injury, has recently shown potential for reducing unnecessary CT scans after pediatric mild head injury. Capillary sampling in children is commonly used when venous sampling fails or is inappropriate. We present reference values for both venous and capillary samples of protein S100B in children. Methods: Neurologically healthy children aged 1–16, scheduled for minor surgery requiring general anesthesia, were prospectively included. Samples for S100B were drawn before (venous) and after (venous and capillary) sedation. Results: Serum values of 455 children (255 boys, 200 girls) aged 1–14 were computed. S100B was higher in younger children for both venous (r = − 0.32) and capillary samples (r = − 0.28). Reference levels for children aged 1 and 2 were significantly higher than for children aged 3–14 years (venous 0.15 μg/L, capillary 0.37 μg/L). For capillary blood, a gender difference was found in the youngest age groups. Conclusions: We present reference values for venous and capillary S100B in healthy children. These results can be utilized when considering future studies on pediatric head injury and S100B levels.
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