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  • 1.
    Eriksson, Hannah K.
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Nordström, Jakob
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Gabrysch, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Hailer, Nils P.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Lazarinis, Stergios
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Does the Alpha-defensin Immunoassay or the Lateral Flow Test Have Better Diagnostic Value for Periprosthetic Joint Infection?: A Systematic Review2018In: Clinical Orthopaedics and Related Research, ISSN 0009-921X, E-ISSN 1528-1132, Vol. 476, no 5, p. 1065-1072Article, review/survey (Refereed)
    Abstract [en]

    Background: Measuring alpha-defensin concentrations in synovial fluid may help to diagnose periprosthetic joint infection (PJI). There are two commercially available methods for measuring alpha-defensin in synovial fluid: the enzyme-linked immunosorbent assay-based Synovasure (R) alpha-defensin immunoassay, which gives a numeric readout within 24 hours, and the Synovasure lateral flow test, which gives a binary readout within 20 minutes. There is no compilation of the existing literature to support the use of one of these two tests over the other.

    Questions/purposes: Does the immunoassay or the lateral flow test have better diagnostic value (sensitivity and specificity) in diagnosing PJI?

    Methods: We followed PRISMA guidelines and identified all studies on alpha-defensin concentration in synovial fluid as a PJI diagnostic marker, indexed to April 14, 2017, in PubMed, JSTOR, Google Scholar, and OVID databases. The search retrieved 1578 records. All prospective and retrospective studies on alpha-defensin as a PJI marker (PJI classified according to the criteria of the Musculoskeletal Infection Society) after THA or TKA were included in the analysis. All studies used only one of the two commercially available test methods, but none of them was comparative. After excluding studies with overlapping patient populations, four studies investigating the alpha-defensin immunoassay and three investigating the lateral flow test remained. Alpha-defensin immunoassay studies included 482 joints and lateral flow test studies included 119. The quality of the trials was assessed according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. The heterogeneity among studies was evaluated by the I-2 index, indicating that the heterogeneity of the included studies was low. Pooled sensitivity, specificity, positive and negative likelihood ratios, and receiver operating curves were calculated for each method and compared with each other.

    Results: The alpha-defensin immunoassay had superior overall diagnostic value compared with the lateral flow test (area under the curve, 0.98 versus 0.75) with higher sensitivity (96% [90%-98%] versus 71% [55%-83%], p < 0.001), but no difference in specificity with the numbers available (96% [93%-97%] versus 90% [81%-95%], p = 0.060).

    Conclusions: Measurement of alpha-defensin in synovial fluid is a valuable complement to existing diagnostic criteria, and the immunoassay test detects PJI more accurately than the lateral flow test. The lateral flow test has lower sensitivity, making it difficult to rule out infection, but its relatively high specificity combined with the advantage of a quick response time can make it useful to rule in infection perioperatively.

    Level of Evidence: Level III, diagnostic study.

  • 2. Ernst, Diana
    et al.
    Widera, Christian
    Baerlecken, Niklas T
    Schlumberger, Wolfgang
    Daehnrich, Cornelia
    Schmidt, Reinhold E
    Gabrysch, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Witte, Torsten
    Antibodies against MYC-Associated Zinc Finger Protein: An Independent Marker in Acute Coronary Syndrome?2017In: Frontiers in Immunology, ISSN 1664-3224, E-ISSN 1664-3224, Vol. 8, article id 1595Article in journal (Refereed)
    Abstract [en]

    Introduction: Atherosclerosis is considered the pathophysiology underlying cardiovascular (CVD), cerebrovascular, and peripheral vascular diseases. Evidence supporting an autoimmune component is emerging, with imaging studies correlating MYC-associated zinc finger protein antibody (MAZ-Ab) optical density (OD) with plaque activity. This study compares MAZ-Ab OD on ELISA testing among patients presenting with acute coronary syndromes (ACSs) to healthy controls and investigates the association of MAZ-Ab to traditional CVD risk factors.

    Methods: Patients admitted with ACSs between August 2007 and July 2011 were included. Serum samples taken at presentation were retrospectively tested for MAZ-Ab and compared with serum from healthy volunteers with no CVD risk factors. Large-scale assessment of post-ACS prognostic relevance was performed using the established PLATO cohort.

    Results:  = 0.436).

    Conclusion: MAZ-Ab OD was higher or all ACS phenotypes compared with controls. Given current understanding of MAZ-Ab function, these findings support an autoimmune component to CVD independent of conventional risk factors and indeed the extent of end-organ damage.

  • 3.
    Gabrysch, Katja
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Analysis and Probability Theory.
    Convergence of directed random graphs to the Poisson-weighted infinite tree2016In: Journal of Applied Probability, ISSN 0021-9002, E-ISSN 1475-6072, Vol. 53, no 2, p. 463-474Article in journal (Refereed)
    Abstract [en]

    We consider a directed graph on the integers with a directed edge from vertex i to j present with probability n-1, whenever i<j, independently of all other edges. Moreover, to each edge (i,j) we assign weight n-1(j - i). We show that the closure of vertex 0 in such a weighted random graph converges in distribution to the Poisson-weighted infinite tree as n→∞. In addition, we derive limit theorems for the length of the longest path in the subgraph of the Poisson-weighted infinite tree which has all vertices at weighted distance of at most ρ from the root.

  • 4.
    Gabrysch, Katja
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Analysis and Probability Theory.
    Distribution of the smallest visited point in a greedy walk on the line2016In: Journal of Applied Probability, ISSN 0021-9002, E-ISSN 1475-6072, Vol. 53, no 3, p. 880-887Article in journal (Refereed)
    Abstract [en]

    We consider a greedy walk on a Poisson process on the real line. It is known that the walk does not visit all points of the process. In this paper we first obtain some useful independence properties associated with this process which enable us to compute the distribution of the sequence of indices of visited points. Given that the walk tends to +∞, we find the distribution of the number of visited points in the negative half-line, as well as the distribution of the time at which the walk achieves its minimum.

  • 5.
    Gabrysch, Katja
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Analysis and Probability Theory.
    Thörnblad, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Analysis and Probability Theory.
    The greedy walk on an inhomogeneous Poisson process2018In: Electronic Communications in Probability, ISSN 1083-589X, E-ISSN 1083-589X, Vol. 23, article id 14Article in journal (Refereed)
    Abstract [en]

    The greedy walk is a deterministic walk that always moves from its current position to the nearest not yet visited point. In this paper we consider the greedy walk on an inhomogeneous Poisson point process on the real line. We prove that the property of visiting all points of the point process satisfies a 0-1 law and determine explicit sufficient and necessary conditions on the mean measure of the point process for this to happen. Moreover, we provide precise results on threshold functions for the property of visiting all points.

  • 6.
    Konstantopoulos, Takis
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Analysis and Probability Theory.
    Gabrysch, Katja
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Analysis and Probability Theory.
    Convergence to the Tracy-Widom distribution for longest paths in a directed random graph2013In: Latin American Journal of Probability and Mathematical Statistics, ISSN 1980-0436, E-ISSN 1980-0436, Vol. 10, no 2, p. 711-730Article in journal (Refereed)
    Abstract [en]

    We consider a directed graph on the 2-dimensional integer lattice, placing a directed edge from vertex (i(1), i(2)) to (j(1), j(2)), whenever i(1) <= j(1), i(2) <= j(2), with probability p, independently for each such pair of vertices. Let L-n,L-m denote the maximum length of all paths contained in an n x m rectangle. We show that there is a positive exponent a, such that, if m/n(a) -> 1, as n -> infinity, then a properly centered/rescaled version of L-n,L-m converges weakly to the Tracy-Widom distribution. A generalization to graphs with non-constant probabilities is also discussed.

  • 7.
    Lindholm, Daniel P
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Gabrysch, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Storey, Robert F
    Department of Cardiovascular Science, University of Sheffield, Sheffield, United Kingdom.
    Himmelmann, Anders
    AstraZeneca Research and Development, Mölndal, Sweden.
    Cannon, Christopher P
    Cardiovascular Division, Brigham and Women’s Hospital, Boston, Massachusetts, USA; Baim Clinical Research Institute, Boston, Massachusetts, USA.
    Mahaffey, Kenneth W
    Stanford Center for Clinical Research, Stanford School of Medicine, Stanford, California, USA.
    Steg, Philippe Gabriel
    Assistance Publique-Hôpitaux de Paris; Département Hospitalo-Universitaire FIRE, Hôpital Bichat, Paris, France; Université Paris-Diderot, Sorbonne-Paris Cité, Paris, France; NHLI Imperial College, ICMS, Royal Brompton Hospital, London, United Kingdom.
    Held, Claes
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Association of Multiple Biomarkers With Risk of All-Cause and Cause-Specific Mortality After Acute Coronary Syndromes: A Secondary Analysis of the PLATO Biomarker Study2018In: JAMA cardiology, ISSN 2380-6583, E-ISSN 2380-6591, Vol. 3, no 12, p. 1160-1166Article in journal (Refereed)
    Abstract [en]

    Importance: Mortality remains at about 5% within a year after an acute coronary syndrome event. Prior studies have assessed biomarkers in relation to all-cause or cardiovascular deaths but not across multiple causes.

    Objective: To assess if different biomarkers provide information about the risk for all-cause and cause-specific mortality.

    Design, Setting, and Participants: The Platelet Inhibition and Patient Outcomes (PLATO) trial randomized 18 624 patients with acute coronary syndrome to ticagrelor or clopidogrel from October 2006 through July 2008. In this secondary analysis biomarker substudy, 17 095 patients participated.

    Main Outcomes and Measures: Death due to myocardial infarction, heart failure, sudden cardiac death/arrhythmia, bleeding, procedures, other vascular causes, and nonvascular causes, as well as all-cause death.

    Exposures: At baseline, levels of cystatin-C, growth differentiation factor-15 (GDF-15), high-sensitivity C-reactive protein, high-sensitivity troponin I and T, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were determined.

    Results: The median (interquartile range) age of patients was 62.0 (54.0-71.0) years. Of 17 095 patients, 782 (4.6%) died during follow-up. The continuous associations between biomarkers and all-cause and cause-specific mortality were modeled using Cox models and presented as hazard ratio (HR) comparing the upper vs lower quartile. For all-cause mortality, NT-proBNP and GDF-15 were the strongest markers with adjusted HRs of 2.96 (95% CI, 2.33-3.76) and 2.65 (95% CI, 2.17-3.24), respectively. Concerning death due to heart failure, NT-proBNP was associated with an 8-fold and C-reactive protein, GDF-15, and cystatin-C, with a 3-fold increase in risk. Regarding sudden cardiac death/arrhythmia, NT-proBNP was associated with a 4-fold increased risk and GDF-15 with a doubling in risk. Growth differentiation factor-15 had the strongest associations with other vascular and nonvascular deaths and was possibly associated with death due to major bleeding (HR, 4.91; 95% CI, 1.39-17.43).

    Conclusions and Relevance: In patients with acute coronary syndrome, baseline levels of NT-proBNP and GDF-15 were strong markers associated with all-cause death based on their associations with death due to heart failure as well as due to arrhythmia and sudden cardiac death. Growth differentiation factor-15 had the strongest associations with death due to other vascular or nonvascular causes and possibly with death due to bleeding.

    Trial Registration: ClinicalTrials.gov Identifier: NCT00391872.

  • 8.
    Sumaya, Wael
    et al.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England..
    Wallentin, Lars
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    James, Stefan K.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Siegbahn, Agneta
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Clinical Chemistry.
    Gabrysch, Katja
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Himmelmann, Anders
    AstraZeneca Res & Dev, Gothenburg, Sweden..
    Ajjan, Ramzi A.
    Univ Leeds, Leeds Inst Cardiovasc & Metab Med, Leeds, W Yorkshire, England..
    Storey, Robert F.
    Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England..
    Fibrin clot properties independently predict adverse clinical outcome following acute coronary syndrome: a PLATO substudy2018In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 39, no 13, p. 1078-1085Article in journal (Other academic)
    Abstract [en]

    Aims To determine whether fibrin clot properties are associated with clinical outcomes following acute coronary syndrome (ACS).

    Methods and results Plasma samples were collected at hospital discharge from 4354 ACS patients randomized to clopidogrel or ticagrelor in the PLATelet inhibition and patient Outcomes (PLATO) trial. A validated turbidimetric assay was employed to study plasma clot lysis time and maximum turbidity (a measure of clot density). One-year rates of cardiovascular (CV) death, spontaneous myocardial infarction (MI) and PLATO-defined major bleeding events were assessed after sample collection. Hazard ratios (HRs) were estimated using Cox proportional hazards models. After adjusting for CV risk factors, each 50% increase in lysis time was associated with CV death/spontaneous MI [HR 1.17, 95% confidence interval (CI) 1.05-1.31; P < 0.01] and CV death alone (HR 1.36, 95% CI 1.17-1.59; P < 0.001). Similarly, each 50% increase in maximum turbidity was associated with increased risk of CV death (HR 1.24, 95% CI 1.03-1.50; P = 0.024). After adjustment for other prognostic biomarkers (leukocyte count, high-sensitivity C-reactive protein, high-sensitivity troponin T, cystatin C, N-terminal pro B-type natriuretic peptide, and growth differentiation factor15), the association with CV death remained significant for lysis time (HR 1.2, 95% CI 1.01-1.42; P = 0.042) but not for maximum turbidity. These associations were consistent regardless of randomized antiplatelet treatment (all interaction P > 0.05). Neither lysis time nor maximum turbidity was associated with major bleeding events.

    Conclusion Fibrin clots that are resistant to lysis independently predict adverse outcome in ACS patients. Novel therapies targeting fibrin clot properties might be a new avenue for improving prognosis in patients with ACS.

  • 9.
    Trinajstic, Katja
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Analysis and Probability Theory.
    Convergence to the Tracy-Widom distribution for longest paths in a directed random graph2014Licentiate thesis, monograph (Other academic)
1 - 9 of 9
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