Papers by Søren Kristensen
PLOS ONE, Jan 14, 2019
Multiple myeloma (MM) patients have increased risk of developing venous thromboembolism, but the ... more Multiple myeloma (MM) patients have increased risk of developing venous thromboembolism, but the underlying mechanisms and the effect on the coagulation system of the disease and the current cancer therapies are not known. It is possible that cancer-associated extracellular vesicles (EV), carrying tissue factor (TF) and procoagulant phospholipids (PPL) may play a role in thrombogenesis. The aim of this study was to perform an in-depth analysis of procoagulant activity of small and large EVs isolated from 20 MM patients at diagnosis and after receiving first-line treatment compared with 20 healthy control subjects. Differential ultracentrifugation at 20,000 × g and 100,000 × g were used to isolate EVs for quantitative and phenotypical analysis through nanoparticle tracking analysis, Western blotting and transmission electron microscopy. The isolated EVs were analyzed for procoagulant activity using the calibrated automated thrombogram technique, a factor Xa-based activity assay, and the STA Procoag-PPL assay. In general, MM patients contained more EVs, and immunoelectron microscopy confirmed the presence of CD9-and CD38-positive EVs. EVs in the 20,000 × g pellets from MM patients exerted procoagulant activity visualized by increased thrombin generation and both TF and PPL activity. This effect diminished during treatment, with the most prominent effect observed in the high-dose chemotherapy eligible patients after induction therapy with bortezomib, cyclophosphamide, and dexamethasone. In conclusion, the EVs in patients with MM carrying TF and PPL are thus capable of exerting procoagulant activity.
Journal of extracellular vesicles, Apr 18, 2013
only one of eight Tol/Pal transposon mutants. Treatment of Francisella bacteria with antimicrobia... more only one of eight Tol/Pal transposon mutants. Treatment of Francisella bacteria with antimicrobial peptides (human-beta defensin 2 (hBD2) and hBD3, the human cathelicidin LL-37 and colistin) as well as growth under high salt conditions increased the production of OMVs in Francisella. Thus, membrane-destabilising treatments, such as high salt, antimicrobial peptides or Tol/Pal mutants, result in increased Francisella OMV production as well as increased biofilm production.
Sports Medicine International Open
The effect of long gaming sessions on energy intake, caffeine intake, blood pressure, heart rate,... more The effect of long gaming sessions on energy intake, caffeine intake, blood pressure, heart rate, heart rate variability, and biochemical cardiac injury markers is unknown. The objective of this exploratory study was to investigate the changes in healthy male adults during two consecutive 18-hour sedentary video gaming sessions. Nine participants were enrolled in the study. Energy intake was noted in food diaries. Heart rate variability was monitored continuously; blood pressure and cardiac injury markers were measured every three to six hours. During the 42-hour study, the participants had an energy and caffeine intake of 8004.9 kcal and 1354.4 mg, respectively. The participants had a significant decrease in energy intake in the second session (p=0.01). A strong, negative correlation was found between body mass index and total energy intake (R=–0.84, p=0.005) and waist circumference and total energy intake (R=–0.70, p=0.036) in the first session. No nightly dip in blood pressure or...
Thyroid Research
Pregnancy induces physiological changes that affect the risk of thrombosis and thyroid disease. I... more Pregnancy induces physiological changes that affect the risk of thrombosis and thyroid disease. In this hypothesis-generating review, the physiological changes in the coagulation system and in thyroid function during a normal pregnancy are described, and the incidence of venous thromboembolism (VTE) and thyroid disease in and after a pregnancy are compared and discussed. Furthermore, evidence regarding the association between thyroid disease and VTE in non-pregnant individuals is scrutinized. In conclusion, a normal pregnancy entails hormonal changes, which influence the onset of VTE and thyroid disease. Current evidence suggests an association between thyroid disease and VTE in non-pregnant individuals. This review proposes the hypothesis that maternal thyroid disease associates with VTE in pregnant women and call for future research studies on this subject. If an association exists in pregnant women specifically, such findings may have clinical implications regarding strategies fo...
Sensors, 2019
Back scatter interferometry (BSI) is a sensitive method for detecting changes in the bulk refract... more Back scatter interferometry (BSI) is a sensitive method for detecting changes in the bulk refractive index of a solution in a microfluidic system. Here we demonstrate that BSI can be used to directly detect enzymatic reactions and, for the first time, derive kinetic parameters. While many methods in biomedical assays rely on detectable biproducts to produce a signal, direct detection is possible if the substrate or the product exert distinct differences in their specific refractive index so that the total refractive index changes during the enzymatic reaction. In this study, both the conversion of glucose to glucose-6-phosphate, catalyzed by hexokinase, and the conversion of adenosine-triphosphate to adenosine di-phosphate and mono-phosphate, catalyzed by apyrase, were monitored by BSI. When adding hexokinase to glucose solutions containing adenosine-triphosphate, the conversion can be directly followed by BSI, which shows the increasing refractive index and a final plateau correspo...
Research and Practice in Thrombosis and Haemostasis, 2022
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Research and Practice in Thrombosis and Haemostasis, 2022
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-... more This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Thrombosis Research, 2021
COVID-19 vaccination Adverse events Anti PF-4 antibodies Thrombocytopenia μl), and patient 11 had... more COVID-19 vaccination Adverse events Anti PF-4 antibodies Thrombocytopenia μl), and patient 11 had a reduced platelet count (150,000 pr μl) compared with the level measured two months earlier (266,000 pr μl).
The Analyst, Jan 7, 2015
Back Scatter Interferometry (BSI) has been proposed to be a highly sensitive and versatile refrac... more Back Scatter Interferometry (BSI) has been proposed to be a highly sensitive and versatile refractive index sensor usable for analytical detection of biomarker and protein interactions in solution. However the existing literature on BSI lacks a physical explanation of why protein interactions in general should contribute to the BSI signal. We have established a BSI system to investigate this subject in further detail. We contribute with a thorough analysis of the robustness of the sensor including unwanted contributions to the interferometric signal caused by temperature variation and dissolved gasses. We report a limit of the effective minimum detectability of refractive index at the 10(-7) level. Long term stability was examined by simultaneously monitoring the temperature inside the capillary revealing an average drift of 2.0 × 10(-7) per hour. Finally we show that measurements on protein A incubated with immunoglobulin G do not result in a signal that can be attributed to bindin...
Clinical Chemistry, 2008
The funding organizations played no role in the design of the study, choice of enrolled patients,... more The funding organizations played no role in the design of the study, choice of enrolled patients, review and interpretation of data, or preparation or approval of manuscript. References 1. Janssen AJM, Trijbels FJM, Sengers RCA, Smeitink JAM, van den Heuvel LP, Wintjes LTM, et al. Spectrophotometric assay for complex I of the respiratory chain in tissue samples and cultured fibroblasts.
Journal of Thrombosis and Haemostasis, 2013
Diseases of the Esophagus, 2013
The association between venous thromboembolism and chemotherapy for esophagogastric cancer is wel... more The association between venous thromboembolism and chemotherapy for esophagogastric cancer is well known in patients treated with palliative intent. Whether this risk extends to the neoadjuvant and perioperative setting is unclear. A retrospective interrogation of databases of patients receiving perioperative chemotherapy for potentially curative intent at the Leicester (2006-2011) and Nottingham (2004-2011) esophagogastric cancer centers was performed. Thromboembolic events were diagnosed in 48 of 384 patients (12.5%), 21 (5.5%) at presentation, 12 (3%) during neoadjuvant chemotherapy, and 15 (3.9%) in the postoperative period. There were no deaths from thromboembolic disease. By site these comprised catheter-related axillary vein thrombosis in 7 patients, deep venous thrombosis in 12 patients, and pulmonary embolism in 29 patients. Twenty-five of the 29 pulmonary emboli were incidental findings on staging computed tomography imaging. Combination chemotherapy with epirubicin, cisplatin, and capecitabine appeared to carry the greatest risk for the development of thromboembolism. Seven of the 12 patients (58%) who developed thromboembolism during neoadjuvant chemotherapy did not proceed to surgery because of deterioration in performance status. Preoperative thromboembolic disease resulted in a significant increase in the interval between chemotherapy and surgery, but did not influence either length of hospital stay or survival. Venous thromboembolism will develop in 12.5% of patients treated with potentially curative intent. This adverse event can occur at any time during the patient journey. In contrast to the commonly held view, this did not translate into a poorer prognosis.
Thrombosis Research, May 1, 2015
Prospective studies of chemotherapy-associated VTE in cancer patients undergoing neoadjuvant chem... more Prospective studies of chemotherapy-associated VTE in cancer patients undergoing neoadjuvant chemotherapy in combination with curative intended surgery have not been reported for upper gastrointestinal cancer. In this clinical prospective study, we sought to estimate the incidence of VTE in esophagogastric cancer (OEC) patients scheduled for a specific perioperative chemotherapy regime: oxaliplatin, capecitabine, and epirubicin, (EXE) and curative intended surgery. Material and Methods: A total of 129 consecutive OEC patients were examined using state-of-the-art bilateral compression ultrasound (biCUS) for deep vein thrombosis (DVT) before undergoing preoperative chemotherapy, surgery, and postoperative chemotherapy. In addition 79 were also consecutively scanned at baseline for pulmonary embolism (PE) using state-of-the-art computer tomography pulmonary angiography (CTPA). Results: There were 21 VTE cases throughout the course of treatment (16%, 95% confidence interval [95% CI]: 10-24%) among the patients examined using both biCUS and CTPA. Fourteen of 21 VTE was incidental (68%, 95% CI: 43-85) and 7 VTE events was symptomatic (33%, 15-57). The median overall survival was 18 months (95% CI: 13-24) in patients without any VTE and 14 months (95% CI: 7-30, P = 0.820) in patients with VTE. The cancer stage (adjusted odds ratio [OR]: 5.2, 95% CI: 1-21, p = 0.002) and gastric cancer (OR 6.4, 95% CI: 2-21, P = 0.002) was a significant predictor of VTE. Conclusion: The incidence of VTE in patients undergoing EXE neoadjuvant chemotherapy was high, particularly among patients with initial stage III and IV cancers. In addition, a substantial number of chemotherapy-related VTE cases were asymptomatic.
Journal of Thrombosis and Haemostasis, Apr 1, 2015
Background: The differences in outcome among cancer patients with incidental vs. symptomatic veno... more Background: The differences in outcome among cancer patients with incidental vs. symptomatic venous thromboembolism (VTE) are unknown. In this study, patients with extrahepatic pancreaticobiliary tract cancer (PBC) were selected for a prospective cohort study between February 2008 and February 2011. Methods: At the time of cancer diagnosis, all patients were examined for deep vein thrombosis with bilateral compression ultrasonography (biCUS). Computed tomography pulmonary angiography was also performed to diagnose pulmonary embolisms. After inclusion, the patients were followed up with clinical examinations, blood collections, and biCUS. Results: A total of 121 PBC patients were enrolled. At the time of cancer diagnosis, 15 patients had experienced a VTE (12.4%, 95% confidence interval [CI] 7.1-19.6), including six symptomatic and nine incidental cases. A total of 25 first-time VTE events were identified (20.7%; 95% CI 13.8-29.0). Patients with a VTE had reduced survival, with a median overall survival (OS) of 4.4 months (95% CI 2.2-11.5). The median OS of the patients with incidental VTE was 3.0 months (95% CI 0.1-15.0), which was not different from the median OS of the patients with symptomatic VTE (5.0 months; 95% CI 2.1-14.5). The median OS was 11.9 months (95% CI 8.1-14.7) in the PBC patients with no VTEs. Conclusion: The occurrence of a VTE event in a PBC patient within the first months of the disease is associated with significantly increased mortality.
Thrombosis Research, Apr 1, 2021
International Journal of Molecular Sciences, Jan 28, 2020
Cancer-associated venous thrombosis (VTE) increases mortality and morbidity. However, limited too... more Cancer-associated venous thrombosis (VTE) increases mortality and morbidity. However, limited tools are available to identify high risk patients. Upon activation, neutrophils release their content through different mechanisms, thereby prompting thrombosis. We explored plasma microRNAs (miRNAs) and neutrophil activation markers to predict VTE in pancreatic ductal adenocarcinoma (PDAC) and distal extrahepatic cholangiocarcinoma (DECC). Twenty-six PDAC and 6 DECC patients recruited at cancer diagnosis, were examined for deep vein thrombosis and pulmonary embolisms, and were then followed-up with clinical examinations, blood collections, and biCUS. Ten patients developed VTE and were compared with 22 age-and sex-matched controls. miRNA expression levels were measured at diagnosis and right before VTE, and neutrophil activation markers (cell-free DNA, nucleosomes, calprotectin, and myeloperoxidase) were measured in every sample obtained during follow-up. We obtained a profile of 7 miRNAs able to estimate the risk of future VTE at diagnosis (AUC = 0.95; 95% Confidence Interval (CI) (0.987, 1)) with targets involved in the pancreatic cancer and complement and coagulation cascades pathways. Seven miRNAs were up-or down-regulated before VTE compared with diagnosis. We obtained a predictive model of VTE with calprotectin as predictor (AUC = 0.77; 95% CI (0.57, 0.95)). This is the first study that addresses the ability of plasma miRNAs and neutrophil activation markers to predict VTE in PDAC and DECC.
Multiple myeloma (MM) is an incurable hematological cancer. It is preceded by monoclonal gammopat... more Multiple myeloma (MM) is an incurable hematological cancer. It is preceded by monoclonal gammopathy of uncertain significance (MGUS), an asymptomatic phase. It has been demonstrated that early detection increases the 5-year survival rate. However, blood-based biomarkers that enable early disease detection are lacking. Metabolomic and lipoprotein subfraction variable profiling is gaining traction to expand our understanding of disease states and, more specifically, for identifying diagnostic markers in patients with hematological cancers. This study aims to enhance our understanding of multiple myeloma (MM) and identify candidate metabolites, allowing for more effective preventative treatment. Serum was collected from 25 healthy controls, 20 patients with MGUS, and 30 patients with MM. 1H-NMR (nuclear magnetic resonance) spectroscopy was utilized to evaluate serum samples. The metabolite concentrations were examined using multivariate, univariate, and pathway analysis. Metabolic prof...
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Papers by Søren Kristensen