Changes in nitric oxide inhibitors and mortality in critically ill patients: a cohort study.

Background: Optimal balance between macro- and microcirculation in critically ill patients is crucial for ensuring optimal organ perfusion. Nitric oxide (NO) is a regulator of vascular hemostasis and tone. The availability of NO is controlled by asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), and the availability of the NO substrates arginine and homoarginine.

Tenascin-C in patients with central nervous system infections.

Background: The extracellular matrix protein tenascin-C has been discovered to be an important regulator of the response to tissue injury and repair in cerebrovascular diseases. This study investigated if tenascin-C is released in response to infections in the central nervous system (CNS).

Methods: Tenascin-C concentration in the cerebrospinal fluid (CSF) was measured in patients, (>18 years) with and without CNS infections, admitted to a department of infectious diseases in Denmark.

Neutrophil Reactivity Intensity and misclassification of immature granulocytes.

Introduction: Immature granulocyte percentage (IG%) is an important biomarker for infection control. We observed spurious cases where the IG% was dramatically underestimated on the automated Sysmex XN-series hehmatology analyzer compared with manual differential. These cases were associated with high values of "Neutrophil Reactivity Intensity" (NEUT-RI), which should reflect the metabolic activity of the neutrophils.

Applying WHO2013 diagnostic criteria for gestational diabetes mellitus reveals currently untreated women at increased risk.

Aims: To estimate the prevalence of gestational diabetes mellitus (GDM) in a Danish cohort comparing the current Danish versus the WHO2013 diagnostic criteria, and to evaluate adverse pregnancy outcomes among currently untreated women in the gap between the diagnostic thresholds.

Methods: Diagnostic testing was performed by a 75 g oral glucose tolerance test (OGTT) at 24-28 weeks' gestation in a cohort of pregnant women. GDM diagnosis was based on the current Danish criterion (2-h glucose ≥ 9.

Pentraxin 3 in the cerebrospinal fluid during central nervous system infections: A retrospective cohort study.

The present study describes diagnostic and prognostic abilities of Cerebrospinal fluid (CSF) Pentraxin 3 (PTX3) in central nervous system (CNS) infections. CSF PTX3 was measured retrospectively from 174 patients admitted under suspicion of CNS infection. Medians, ROC curves and Youdens index was calculated.

Sensitivity and performance of three novel quantitative assays of SARS-CoV-2 nucleoprotein in blood.

To assess if SARS-CoV-2 (COVID-19) systemic disease can be determined by available nucleoprotein assays, we compared the performance of three commercial SARS-CoV-2 nucleoprotein (N) assays in plasma. A total of 272 plasma samples collected in the period November-December 2021 were analyzed by the methods Simoa SARS CoV-2 N Protein Advantage Kit [Quanterix Simoa], Solsten SARS-CoV-2 Antigen enzyme immunosorbent assay (ELISA) [Solsten ELISA], and Elecsys SARS-CoV-2 Antigen electrochemiluminescence immunoassay [Elecsys ECLIA]. Additionally, a dilution series of inactivated virus culture was analyzed by the three assays.

Long-Term Comparison of 7 SARS-CoV-2 Antibody Assays in the North Zealand Covid-19 Cohort.

Background: Throughout the coronavirus disease 2019 (Covid-19) pandemic numerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody assays have been approved through Emergency Use Authorization and require further evaluation of sensitivity and specificity in clinical laboratory settings prior to implementation.

Methods: We included 1733 samples from 375 PCR-confirmed SARS-CoV-2-positive individuals of the North Zealand Covid-19 Cohort in an 8-month period. We investigated diagnostic sensitivity and specificity against consensus and PCR and interassay agreement over time for 5 SARS-CoV-2 immunoassays [Roche-nucleocapsid (NC)-total, Roche-receptor binding domain (RBD)-total, Siemens-RBD-IgG, Siemens-RBD-total, Thermo Fisher Scientific (TFS)-RBD-IgG] commercially available on automated platforms and 2 ELISA assays (TFS-RBD-total, Wantai-RBD-total).

Evaluation of a New Automated Routine Measurement for Serum Adjusted Ionized Calcium (at pH 7.4) in Patients Suspected of Calcium Metabolic Disease.

Background: Total calcium is a less accurate test in predicting ionized calcium (Ca2+) in patients suspected of calcium metabolic disease. Nevertheless, total calcium continues to be used as routine measurement instead of adjusted Ca2+ (at pH 7.4).

Feasibility of single-cell analysis of model cancer and foetal cells in blood after isolation by cell picking.

The objective of the present feasibility study was to transfer single cell line cells to either microscopy slides for downstream immune characterization or to polymerase chain reaction tubes for downstream DNA quantitation. Tumour cell lines, SKBR3 and MCF7 and trophoblast cell line JEG-3 were spiked in healthy donor blood. The CytoTrack system was used to scan the spiked blood samples to identify target cells.

Clean Colorectum at Diagnostic Colonoscopy: Subsequent Detection of Extracolonic Malignancies by Plasma Protein Biomarkers?

Introduction: Most of the subjects undergoing diagnostic colonoscopy do not have neoplastic bowel lesions. Potentially, some of the symptoms may therefore be caused by extracolonic malignancy, and subjects with persisting symptoms may need subsequent examinations. Blood-based, cancer-associated biomarkers may aid in directing the examinations for other specific malignant diseases.

CytoTrack Analysis Reveals Low Presence of Circulating Tumor Cells in the Perioperative Period in Patients with Non-metastatic Colorectal Cancer.

Background/aim: Detection of circulating tumor cells in the perioperative period predicts poor prognosis in patients with colorectal cancer. There is only one Food and Drug Administration-approved method for such detection, CellSearch, for which results have been inconsistent. A new immunological method, CytoTrack, has shown promising results in patients with breast cancer.

Detection of colorectal neoplasia: Combination of eight blood-based, cancer-associated protein biomarkers.

Serological biomarkers may be an option for early detection of colorectal cancer (CRC). The present study assessed eight cancer-associated protein biomarkers in plasma from subjects undergoing first time ever colonoscopy due to symptoms attributable to colorectal neoplasia. Plasma AFP, CA19-9, CEA, hs-CRP, CyFra21-1, Ferritin, Galectin-3 and TIMP-1 were determined in EDTA-plasma using the Abbott ARCHITECT® automated immunoassay platform.

Elevated prostate specific antigen and reduced 10-year survival among a cohort of Danish men consecutively referred from primary care to an urological department during 2005-2006.

It remains unclear whether total prostate specific antigen (tPSA) or complex PSA (cPSA) has the best diagnostic performance. Additionally, the utility of percentage free PSA (%fPSA) is still debated. Our objectives were to compare the diagnostic performances of tPSA, cPSA, and %fPSA among patients referred from GP to an Urological Specialist and to investigate prognostic factors and survival in the cohort.

Protocol Outlines for Parts 1 and 2 of the Prospective Endoscopy III Study for the Early Detection of Colorectal Cancer: Validation of a Concept Based on Blood Biomarkers.

Background: Programs for population screening of colorectal cancer (CRC) have been implemented in several countries with fecal immunochemical testing (FIT) as the preferred platform. However, the major obstacle for a feces-based testing method is the limited compliance that reduces the clinical sensitivity for detection of participants with non-symptomatic CRC. Therefore, research approaches have been initiated to develop screening concepts based on biomarkers in blood.

Discovery and Validation of Plasma-Protein Biomarker Panels for the Detection of Colorectal Cancer and Advanced Adenoma in a Danish Collection of Samples from Patients Referred for Diagnostic Colonoscopy.

Background: Well-collected and well-documented sample repositories are necessary for disease biomarker development. The availability of significant numbers of samples with the associated patient information enables biomarker validation to proceed with maximum efficacy and minimum bias. The creation and utilization of such a resource is an important step in the development of blood-based biomarker tests for colorectal cancer.

Cryopreservation of Circulating Tumor Cells for Enumeration and Characterization.

Background: A blood sample containing circulating tumor cells (CTCs) may serve as a surrogate for metastasis in invasive cancer. Cryopreservation will provide new opportunities in management of clinical samples in the laboratory and allow collection of samples over time for future analysis of existing and upcoming cancer biomarkers.

Methods: Blood samples from healthy volunteers were spiked with high (∼500) and low (∼50) number of tumor cells from culture.

Decrease by 50% of plasma IgA tissue transglutaminase antibody concentrations within 2 months after start of gluten-free diet in children with celiac disease used as a confirming diagnostic test.

Background: Histological examination of small bowel biopsies is normally the gold standard for the diagnosis of celiac disease (CD). The objective of this study was to investigate whether the rate of decreases in elevated plasma IgA tissue transglutaminase antibody (IgA-tTG) and/or IgG deamidated gliadin peptides antibody (IgG - DGP) concentrations could be used as a confirming test for CD in children on a gluten-free diet (GFD) when biopsy was omitted in the diagnostic process.

Methods: In this retrospective study we compared children (≤18 years old) with a CD-confirming biopsy (n = 16) to children without a biopsy (n = 18).

Retracing Circulating Tumour Cells for Biomarker Characterization after Enumeration.

Background: Retracing and biomarker characterization of individual circulating tumour cells (CTCs) may potentially contribute to personalized metastatic cancer therapy. This is relevant when a biopsy of the metastasis is complicated or impossible to acquire.

Methods: A novel disc format was used to map and retrace individual CTCs from breast-cancer patients and nucleated cells from healthy blood donors using the CytoTrack platform.

Mapping of HLA- DQ haplotypes in a group of Danish patients with celiac disease.

Background: A cost-effective identification of HLA- DQ risk haplotypes using the single nucleotide polymorphism (SNP) technique has recently been applied in the diagnosis of celiac disease (CD) in four European populations. The objective of the study was to map risk HLA- DQ haplotypes in a group of Danish CD patients using the SNP technique.

Methods: Cohort A: Among 65 patients with gastrointestinal symptoms we compared the HLA- DQ2 and HLA- DQ8 risk haplotypes obtained by the SNP technique (method 1) with results based on a sequence specific primer amplification technique (method 2) and a technique used in an assay from BioDiagene (method 3).

In vitro detection of circulating tumor cells compared by the CytoTrack and CellSearch methods.

Comparison of two methods to detect circulating tumor cells (CTC) CytoTrack and CellSearch through recovery of MCF-7 breast cancer cells, spiked into blood collected from healthy donors. Spiking of a fixed number of EpCAM and pan-cytokeratin positive MCF-7 cells into 7.5 mL donor blood was performed by FACSAria flow sorting.

In vitro validation of an ultra-sensitive scanning fluorescence microscope for analysis of circulating tumor cells.

Analysis of circulating tumor cells (CTC) holds promise of providing liquid biopsies from patients with cancer. However, current methods include enrichment procedures. We present a method (CytoTrack), where CTC from 7.

Assessing HER2 amplification by IHC, FISH, and real-time polymerase chain reaction analysis (real-time PCR) following LCM in formalin-fixed paraffin embedded tissue from 40 women with ovarian cancer.

We compare HER2 receptor amplification analysis by immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and real-time polymerase chain reaction (real-time PCR) DNA copy-number assay following laser capture microdissection (LCM) in formalin-fixed paraffin embedded tissue from 40 women with verified ovarian cancer. We speculate that LCM should result in a more accurate assessment of HER2 amplification in our real-time PCR assay compared with IHC and FISH. HER2 overexpression measured by IHC, FISH, or real-time PCR was found in 5.

The collagen receptor uPARAP/Endo180.

The uPAR-associated protein (uPARAP/Endo180), a type-1 membrane protein belonging to the mannose receptor family, is an endocytic receptor for collagen. Through this endocytic function, the protein takes part in a previously unrecognized mechanism of collagen turnover. uPARAP/Endo180 can bind and internalize both intact and partially degraded collagens.

Dimerization of endogenous MT1-MMP is a regulatory step in the activation of the 72-kDa gelatinase MMP-2 on fibroblasts and fibrosarcoma cells.

The secreted gelatinase matrix metalloprotease-2 (MMP-2) and the membrane-anchored matrix metalloprotease MT1-MMP (MMP-14), are central players in pericellular proteolysis in extracellular matrix degradation. In addition to possessing a direct collagenolytic and gelatinolytic activity, these enzymes take part in a cascade pathway in which MT1-MMP activates the MMP-2 proenzyme. This reaction occurs in an interplay with the matrix metalloprotease inhibitor, TIMP-2, and the proposed mechanism involves two molecules of MT1-MMP in complex with one TIMP-2 molecule.

A composite role of vitronectin and urokinase in the modulation of cell morphology upon expression of the urokinase receptor.

The urokinase receptor, urokinase receptor (uPAR), is a glycosylphosphatidylinositol-anchored membrane protein engaged in pericellular proteolysis and cellular adhesion, migration, and modulation of cell morphology. A direct matrix adhesion is mediated through the binding of uPAR to vitronectin, and this event is followed by downstream effects including changes in the cytoskeletal organization. However, it remains unclear whether the adhesion through uPAR-vitronectin is the only event capable of initiating these morphological rearrangements or whether lateral interactions between uPAR and integrins can induce the same response.