Thor Ueland

• Grannes, Helene; Ueland, Thor; Simeone, Paola; Liani, Rossella; Guagnano, Maria Teresa & Aukrust, Pål [Show all 14 contributors for this article] (2024). Liraglutide and not lifestyle intervention reduces soluble CD163 after comparable weight loss in obese participants with prediabetes or type 2 diabetes mellitus. Cardiovascular Diabetology. ISSN 1475-2840. 23(1). doi: 10.1186/s12933-024-02237-8.
• Ueland, Thor; Butt, Noreen; Lekva, Tove; Ørn, Stein; Manhenke, Cord Arend & Aukrust, Pål [Show all 7 contributors for this article] (2024). High dose statin treatment reduces circulating Dickkopf-1 following acute myocardial infarction. International Journal of Cardiology. ISSN 0167-5273. 406. doi: 10.1016/j.ijcard.2024.132035.
• Farbu, Bjørn Hoftun; Lydersen, Stian; Mohus, Randi Marie; Ueland, Thor; Mollnes, Tom Eirik & Klepstad, Pål [Show all 7 contributors for this article] (2024). The detrimental effects of intestinal injury mediated by inflammation are limited in cardiac arrest patients: A prospective cohort study. Resuscitation Plus. ISSN 2666-5204. 18. doi: 10.1016/j.resplu.2024.100639.
• Gjerde, Kristian Varden; Bartz-Johannessen, Christoffer; Steen, Vidar Martin; Andreassen, Ole; Steen, Nils Eiel & Ueland, Thor [Show all 12 contributors for this article] (2024). Cellular adhesion molecules in drug-naïve and previously medicated patients with schizophrenia-spectrum disorders. Schizophrenia Research. ISSN 0920-9964. 267, p. 223–229. doi: 10.1016/j.schres.2024.03.029.
• Nilsen, Dennis WT; Aarsetoey, Reidun; Poenitz, Volker; Ueland, Thor; Aukrust, Pål & Michelsen, Annika Elisabet [Show all 9 contributors for this article] (2024). Chemokine ligand 18 predicts all-cause mortality in patients hospitalized with chest pain of suspected coronary origin. International Journal of Cardiology: Cardiovascular Risk and Prevention (IJCCRP). ISSN 2772-4875. 21. doi: 10.1016/j.ijcrp.2024.200264.
• Barratt-Due, Andreas; Pettersen, Kristin; Dahl, Tuva Børresdatter; Holter, Jan Cato; Grønli, Renathe Henriksen & Dyrhol-Riise, Anne Ma [Show all 20 contributors for this article] (2024). Escalated complement activation during hospitalization is associated with higher risk of 60-day mortality in SARS-CoV-2-infected patients. Journal of Internal Medicine. ISSN 0954-6820. doi: 10.1111/joim.13783.
• Falch, Camilla Maria; Godang, Kristin; Lekva, Tove; Ueland, Thor; Heck, Ansgar & Bollerslev, Jens [Show all 7 contributors for this article] (2024). Long-term depot specific changes in adipose tissue after treatment of acromegaly. European Journal of Endocrinology (EJE). ISSN 0804-4643. 190(3), p. K37–K42. doi: 10.1093/ejendo/lvae016.
• Kong, Xiang Yi; Lauritzen, Knut Husø; Dahl, Tuva Børresdatter; Holm, Sverre; Olsen, Maria Belland & Skjelland, Mona [Show all 12 contributors for this article] (2024). CD38 deficient mice are not protected from atherosclerosis. Biochemical and Biophysical Research Communications - BBRC. ISSN 0006-291X. 705. doi: 10.1016/j.bbrc.2024.149734.
• Sæther, Linn Sofie; Szabo, Attila; Akkouh, Ibrahim Ahmed; Haatveit, Beathe ; Mohn, Christine & Vaskinn, Anja [Show all 14 contributors for this article] (2024). Cognitive and inflammatory heterogeneity in severe mental illness: Translating findings from blood to brain. Brain, Behavior, and Immunity. ISSN 0889-1591. 118, p. 287–299. doi: 10.1016/j.bbi.2024.03.014.
• Damås, Jan Kristian; Otterdal, Kari; Astrup, Elisabeth; Lekva, Tove; Janardhanan, Jeshina & Michelsen, Annika Elisabet [Show all 9 contributors for this article] (2024). Canonical notch activation in patients with scrub typhus: association with organ dysfunction and poor outcome. Infection. ISSN 0300-8126. doi: 10.1007/s15010-024-02192-2.
• Andreou, Dimitrios; Steen, Nils Eiel; Mørch-Johnsen, Lynn Egeland; Jørgensen, Kjetil Nordbø; Wortinger, Laura Anne & Barth, Claudia [Show all 19 contributors for this article] (2024). Toxoplasma gondii infection associated with inflammasome activation and neuronal injury. Scientific Reports. ISSN 2045-2322. 14(1). doi: 10.1038/s41598-024-55887-9.
• Gregersen, Ida; Narverud, Ingunn; Christensen, Jacob J.; Hovland, Anders Wilhelm; Øyri, Linn Kristin Lie & Ueland, Thor [Show all 11 contributors for this article] (2024). Plasma legumain in familial hypercholesterolemia: associations with statin use and cardiovascular risk markers. Scandinavian Journal of Clinical and Laboratory Investigation. ISSN 0036-5513. doi: 10.1080/00365513.2024.2309617.
• Prapiadou, Savvina; Živković, Luka; Thorand, Barbara; George, Marc J.; Van Der Laan, Sander W & Malik, Rainer [Show all 20 contributors for this article] (2023). Proteogenomic Data Integration Reveals CXCL10 as a Potentially Downstream Causal Mediator for IL-6 Signaling on Atherosclerosis. Circulation. ISSN 0009-7322. 149(9), p. 669–683. doi: 10.1161/CIRCULATIONAHA.123.064974.
• Ueland, Thor; Michelsen, Annika Elisabet; Tveita, Anders; Kåsine, Trine; Dahl, Tuva Børresdatter & Finbråten, Ane-Kristine [Show all 16 contributors for this article] (2023). Coagulopathy and adverse outcomes in hospitalized patients with COVID-19: results from the NOR-Solidarity trial. Research and Practice in Thrombosis and Haemostasis (RPTH). ISSN 2475-0379. 8(1). doi: 10.1016/j.rpth.2023.102289. Full text in Research Archive
• Lekva, Tove; Sundaram, Arvind; Roland, Marie Cecilie; Åsheim, June; Michelsen, Annika Elisabet & Norwitz, Errol R. [Show all 9 contributors for this article] (2023). Platelet and mitochondrial RNA is decreased in plasma-derived extracellular vesicles in women with preeclampsia—an exploratory study. BMC Medicine. ISSN 1741-7015. 21(1). doi: 10.1186/s12916-023-03178-x. Full text in Research Archive
• Mochol, Monika; Taubøll, Erik; Aukrust, Pål; Ueland, Thor; Andreassen, Ole & Svalheim, Sigrid (2023). Serum Markers of Neuronal Damage and Astrocyte Activity in Patients with Chronic Epilepsy: Elevated Levels of Glial Fibrillary Acidic Protein. Acta Neurologica Scandinavica. ISSN 0001-6314. 2023, p. 1–5. doi: 10.1155/2023/7246373. Full text in Research Archive
• Requena Osete, Jordi; Akkouh, Ibrahim Ahmed; Ievglevskyi, Oleksandr; Vandenberghe, Matthieu; Reis de Assis, Denis & Ueland, Thor [Show all 14 contributors for this article] (2023). Characterization of lithium (Li) treated human cortical spheroids (hCS). Molecular Psychiatry. ISSN 1359-4184. 28(7). doi: 10.1038/s41380-023-02300-y.
• Akkouh, Ibrahim Ahmed; Ueland, Thor; Szabo, Attila; Hughes, Timothy; Smeland, Olav Bjerkehagen & Andreassen, Ole [Show all 8 contributors for this article] (2023). Longitudinal Transcriptomic Analysis of Human Cortical Spheroids Identifies Axonal Dysregulation in the Prenatal Brain as a Mediator of Genetic Risk for Schizophrenia. Biological Psychiatry. ISSN 0006-3223. 0, p. 1–12. doi: 10.1016/j.biopsych.2023.08.017. Full text in Research Archive
• Lekva, Tove; Michelsen, Annika Elisabet; Roland, Marie Cecilie; Norwitz, Errol R.; Estensen, Mette-Elise & Olstad, Ole Kristoffer [Show all 11 contributors for this article] (2023). Increased ferroptosis in leukocytes from preeclamptic women involving the long non-coding taurine upregulated gene 1 (TUG1). Journal of Internal Medicine. ISSN 0954-6820. 295(2), p. 181–195. doi: 10.1111/joim.13732. Full text in Research Archive
• Murphy, Sarah Louise Mikalsen; Halvorsen, Bente; Holter, Jan Cato; Huse, Camilla; Tveita, Anders & Trøseid, Marius [Show all 24 contributors for this article] (2023). Circulating markers of extracellular matrix remodelling in severe COVID-19 patients. Journal of Internal Medicine. ISSN 0954-6820. 294(6), p. 784–797. doi: 10.1111/joim.13725. Full text in Research Archive
• Steen, Nils Eiel; Rahman, Zillur; Szabo, Attila; Hindley, Guy; Parker, Nadine & Cheng, Weiqiu [Show all 20 contributors for this article] (2023). Shared Genetic Loci Between Schizophrenia and White Blood Cell Counts Suggest Genetically Determined Systemic Immune Abnormalities. Schizophrenia Bulletin. ISSN 0586-7614. 49(5), p. 1345–1354. doi: 10.1093/schbul/sbad082. Full text in Research Archive
• Hjell, Gabriela; Rokicki, Jaroslav; Szabo, Attila; Holst, Rene; Tesli, Natalia & Bell, Christina [Show all 19 contributors for this article] (2023). Impulsivity across severe mental disorders: a cross-sectional study of immune markers and psychopharmacotherapy. BMC Psychiatry. ISSN 1471-244X. 23(1). doi: 10.1186/s12888-023-05154-4. Full text in Research Archive
• Hindley, Guy; Drange, Ole Kristian; Lin, Aihua; Kutrolli, Gleda; Shadrin, Alexey & Parker, Nadine [Show all 20 contributors for this article] (2023). Cross-trait genome-wide association analysis of C-reactive protein level and psychiatric disorders. Psychoneuroendocrinology. ISSN 0306-4530. 157. doi: 10.1016/j.psyneuen.2023.106368. Full text in Research Archive
• Andersen, Thomas; Ueland, Thor; Aukrust, Pål; Nilsen, Dennis WT; Grundt, Magnea Heidi Jonsdottir & Staines, Harry [Show all 8 contributors for this article] (2023). Procollagen type 1 N-terminal propeptide is associated with adverse outcome in acute chest pain of suspected coronary origin. Frontiers in Cardiovascular Medicine. ISSN 2297-055X. 10. doi: 10.3389/fcvm.2023.1191055. Full text in Research Archive
• Heck, Ansgar; Godang, Kristin; Lekva, Tove; Markussen, Kjersti Normann; De Vincentis, Sara & Ueland, Thor [Show all 7 contributors for this article] (2023). Endocortical Trabecularization in Acromegaly: The Cause for the Paradoxically Increased Vertebral Fracture Risk? JBMR Plus. ISSN 2473-4039. 7(10). doi: 10.1002/jbm4.10787. Full text in Research Archive
• Solberg, Ole Geir; Aaberge, Lars; Bosse, Gerhard; Ueland, Thor; Gullestad, Lars & Aukrust, Pål [Show all 7 contributors for this article] (2023). Microvascular function and inflammatory activation in Takotsubo cardiomyopathy. ESC Heart Failure. ISSN 2055-5822. 10(5), p. 3216–3222. doi: 10.1002/ehf2.14461. Full text in Research Archive
• Heldal, Torbjørn Fossum; Åsberg, Anders; Ueland, Thor; Reisæter, Anna Varberg; Pischke, Soeren & Mollnes, Tom Eirik [Show all 11 contributors for this article] (2023). Systemic inflammation early after kidney transplantation is associated with long-term graft loss: a cohort study. Frontiers in Immunology. ISSN 1664-3224. 14. doi: 10.3389/fimmu.2023.1253991. Full text in Research Archive
• Hansen, Ellen-Sofie; Edvardsen, Magnus; Aukrust, Pål; Ueland, Thor; Hansen, John Bjarne & Brækkan, Sigrid Kufaas [Show all 7 contributors for this article] (2023). Combined effect of high factor VIII levels and high mean platelet volume on the risk of future incident venous thromboembolism. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. doi: 10.1016/j.jtha.2023.06.022. Full text in Research Archive
• Woxholt, Sindre; Ueland, Thor; Aukrust, Pål; Anstensrud, Anne Kristine; Broch, Kaspar & Tøllefsen, Ingvild Maria [Show all 20 contributors for this article] (2023). Cytokine pattern in patients with ST-elevation myocardial infarction treated with the interleukin-6 receptor antagonist tocilizumab. Open heart. ISSN 2053-3624. 10(2), p. 1–8. doi: 10.1136/openhrt-2023-002301. Full text in Research Archive
• Sikkeland, Liv Ingunn Bjoner; Ueland, Thor; Samersaw-Lund, May Brit; Durheim, Michael Thomas & Mollnes, Tom Eirik (2023). A role for the terminal C5-C9 complement pathway in idiopathic pulmonary fibrosis. Frontiers in medicine. ISSN 2296-858X. 10. doi: 10.3389/fmed.2023.1236495. Full text in Research Archive
• Parker, Nadine; Cheng, Weiqiu; Hindley, Guy; O'Connell, Kevin Sean; Karthikeyan, Sandeep & Holen, Børge [Show all 19 contributors for this article] (2023). Genetic Overlap Between Global Cortical Brain Structure, C-Reactive Protein, and White Blood Cell Counts. Biological Psychiatry. ISSN 0006-3223. doi: 10.1016/j.biopsych.2023.06.008. Full text in Research Archive
• Ueland, Thor; Waagsbø, Bjørn; Berge, Rolf Kristian; Trøseid, Marius; Aukrust, Pål & Damås, Jan Kristian (2023). Fatty Acids Composition and HIV Infection: Altered Levels of n-6 Polyunsaturated Fatty Acids Are Associated with Disease Progression. Viruses. ISSN 1999-4915. 15(7). doi: 10.3390/v15071613. Full text in Research Archive
• Bang-Kittilsen, Gry; Egeland, Jens; Ueland, Thor; Andersen, Eivind; Bigseth, Therese Torgersen & Holmen, Tom Langerud [Show all 9 contributors for this article] (2023). The relationship between the brain-derived neurotrophic factor and neurocognitive response to physical exercise in individuals with schizophrenia. Psychoneuroendocrinology. ISSN 0306-4530. 157. doi: 10.1016/j.psyneuen.2023.106356. Show summary

  Physical exercise can improve neurocognition in individuals with schizophrenia, presumably by facilitating neuroplasticity. There is, however, large inter-individual variation in response. The brain-derived neurotrophic factor (BDNF) has been proposed to mediate these effects. The current aim was to investigate the sparsely studied relationship between peripheral resting BDNF and neurocognitive response to physical exercise in individuals with schizophrenia. Method The current study reports secondary analyses of data from a randomized controlled trial (RCT), ClinicalTrials.gov number 02205684, recently reported according to the CONSORT guidelines. Eighty-two individuals with schizophrenia (mean age 37 ± 14 years old, 61% men) were randomly allocated to high-intensity interval training (HIIT) or a comparison group performing low-intensity active video gaming (AVG). Both interventions consisted of 2 sessions/week for 12 weeks. In previously published primary RCT analyses, HIIT and AVG showed comparable small to moderate improvements in neurocognition. We now address the inter-individual variability in neurocognitive response. We apply mediation and moderation analyses for repeated measures designs (MEMORE) and mixed effects models. Results Baseline neurocognition was not significantly correlated with baseline levels of mature BDNF (baseline-mBDNF) or the precursor proBDNF. Nonetheless, baseline-mBDNF , but not baseline proBDNF, moderated the effect of exercise on neurocognition ( p = 0.025) and explained 7% of the variance. The neurocognitive improvement increased with increasing baseline-mBDNF values. The moderating effect of baseline-mBDNF remained significant in a more complex model adding the moderating effects of exercise mode, sex, age, duration of illness and baseline VO 2 max on the outcome (neurocognition). Mean baseline-mBDNF significantly decreased from baseline to post-intervention ( p = 0.036), regardless of exercise mode, differing by sex and associated with improved VO 2 max but not with change in neurocognition. A mediating role of mBDNF on the effect of physical exercise on neurocognition was not supported. Values of proBDNF mainly remained stable from baseline to post-intervention. Conclusion We found that baseline-mBDNF moderated the effect of physical exercise on neurocognition in individuals with schizophrenia and explained a small part of the inter-individual variation in neurocognitive response. Mean mBDNF decreased from baseline to post-intervention, regardless of exercise mode. A mediating role of mBDNF on the effect of exercise on neurocognition was not supported. The inter-individual variation in neurocognitive response and the complex role of peripheral BDNF in physical exercise is still to be elucidated.

• Hope, Sigrun; Nærland, Terje; Kolset, Svein Olav; Ueland, Thor; Andreassen, Ole & Nordstrøm, Marianne (2023). Systemic immune profile in Prader-Willi syndrome: elevated matrix metalloproteinase and myeloperoxidase and reduced macrophage inhibitory factor. Orphanet Journal of Rare Diseases. ISSN 1750-1172. 18(1). doi: 10.1186/s13023-023-02730-5. Full text in Research Archive
• Tønnessen, Theis Christian; Ueland, Thor; Ahmed, Muhammad Shakil; Attramadal, Håvard; Sjaastad, Ivar & Vinge, Leif Erik (2023). Inflammatory augmentation of the delayed type hypersensitivity arthritis mouse model. Basic & Clinical Pharmacology & Toxicology. ISSN 1742-7835. 132(6), p. 545–549. doi: 10.1111/bcpt.13864. Full text in Research Archive
• Edvardsen, Magnus; Hansen, Ellen-Sofie; Ueland, Thor; Aukrust, Pål; Brækkan, Sigrid Kufaas & Morelli, Vania Maris [Show all 7 contributors for this article] (2023). Impact of the von Willebrand factor-ADAMTS-13 axis on the risk of future venous thromboembolism. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 21(5), p. 1227–1237. doi: 10.1016/j.jtha.2023.01.024. Full text in Research Archive
• Falch, Camilla Maria; Arlien-Søborg, Mai Christiansen; Dal, Jakob; Sundaram, Arvind; Michelsen, Annika Elisabet & Ueland, Thor [Show all 11 contributors for this article] (2023). Gene expression profiling of subcutaneous adipose tissue reveals new biomarkers in acromegaly. European Journal of Endocrinology (EJE). ISSN 0804-4643. 188(3), p. 310–321. doi: 10.1093/ejendo/lvad031. Full text in Research Archive
• Swamy, Samantha; Ueland, Thor; Hansen, John Bjarne; Snir, Omri & Brækkan, Sigrid Kufaas (2023). Plasma levels of P-selectin and future risk of incident venous thromboembolism. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 21(9), p. 2451–2460. doi: 10.1016/j.jtha.2023.04.038. Full text in Research Archive
• Reponen, Elina Johanna; Ueland, Thor; Rokicki, Jaroslav; Bettella, Francesco; Aas, Monica & Werner, Maren Caroline Frogner [Show all 10 contributors for this article] (2023). Polygenic risk for schizophrenia and bipolar disorder in relation to cardiovascular biomarkers. European Archives of Psychiatry and Clinical Neuroscience. ISSN 0940-1334. doi: 10.1007/s00406-023-01591-0. Full text in Research Archive Show summary

  Individuals with schizophrenia and bipolar disorder are at an increased risk of cardiovascular disease (CVD), and a range of biomarkers related to CVD risk have been found to be abnormal in these patients. Common genetic factors are a putative underlying mechanism, alongside lifestyle factors and antipsychotic medication. However, the extent to which the altered CVD biomarkers are related to genetic factors involved in schizophrenia and bipolar disorder is unknown. In a sample including 699 patients with schizophrenia, 391 with bipolar disorder, and 822 healthy controls, we evaluated 8 CVD risk biomarkers, including BMI, and fasting plasma levels of CVD biomarkers from a subsample. Polygenic risk scores (PGRS) were obtained from genome-wide associations studies (GWAS) of schizophrenia and bipolar disorder from the Psychiatric Genomics Consortium. The CVD biomarkers were used as outcome variables in linear regression models including schizophrenia and bipolar disorder PGRS as predictors, age, sex, diagnostic category, batch and 10 principal components as covariates, controlling for multiple testing by Bonferroni correction for the number of independent tests. Bipolar disorder PGRS was significantly (p = 0.03) negatively associated with BMI after multiple testing correction, and schizophrenia PGRS was nominally negatively associated with BMI. There were no other significant associations between bipolar or schizophrenia PGRS, and other investigated CVD biomarkers. Despite a range of abnormal CVD risk biomarkers in psychotic disorders, we only found a significant negative association between bipolar disorder PGRS and BMI. This has previously been shown for schizophrenia PGRS and BMI, and warrants further exploration.

• Trøseid, Marius; Holter, Jan Cato; Holm, Kristian; Vestad, Beate; Sazonova, Taisiia & Granerud, Beathe Kiland [Show all 17 contributors for this article] (2023). Gut microbiota composition during hospitalization is associated with 60-day mortality after severe COVID-19. Critical Care. ISSN 1364-8535. 27(1). doi: 10.1186/s13054-023-04356-2. Full text in Research Archive
• Risnes, Ivar; Aukrust, Pål; Lundblad, Runar; Rødevand, Olaf; Ueland, Thor & Rynning, Stein Erik [Show all 7 contributors for this article] (2023). Increased levels of NT-proBNP and troponin T 2 years after coronary artery bypass grafting complicated by mediastinitis. Frontiers in Cardiovascular Medicine. ISSN 2297-055X. 10. doi: 10.3389/fcvm.2023.1008825. Full text in Research Archive
• Bigseth, Therese Torgersen; Engh, John Bjarne Abel; Andersen, Eivind; Bang-Kittilsen, Gry; Egeland, Jens & Falk, Ragnhild Sørum [Show all 12 contributors for this article] (2023). Alterations in inflammatory markers after a 12-week exercise program in individuals with schizophrenia—a randomized controlled trial. Frontiers in Psychiatry. ISSN 1664-0640. 14. doi: 10.3389/fpsyt.2023.1175171. Full text in Research Archive Show summary

  Background: In individuals with schizophrenia, inflammation is associated with depression, somatic comorbidity and reduced quality of life. Physical exercise is known to reduce inflammation in other populations, but we have only limited knowledge in the field of schizophrenia. We assessed inflammatory markers in plasma samples from individuals with schizophrenia participating in an exercise intervention randomized controlled trial. We hypothesized that (i) physical exercise would reduce levels of inflammatory markers and (ii) elevated inflammatory status at baseline would be associated with improvement in cardiorespiratory fitness (CRF) following intervention. Method: Eighty-two individuals with schizophrenia were randomized to a 12-week intervention of either high-intensity interval training (HIIT, n = 43) or active video gaming (AVG, n = 39). Participants were assessed at baseline, post intervention and four months later. The associations between exercise and the inflammatory markers soluble urokinase plasminogen activator receptor, c-reactive protein, tumor necrosis factor (TNF), soluble TNF receptor 1 and interleukin 6 (IL-6) were estimated using linear mixed effect models for repeated measures. For estimating associations between baseline inflammation and change in CRF, we used linear regression models. Results: Our main findings were (i) TNF and IL-6 increased during the intervention period for both groups. Other inflammatory markers did not change during the exercise intervention period; (ii) baseline inflammatory status did not influence change in CRF during intervention, except for a positive association between baseline IL-6 levels and improvements of CRF to post intervention for both groups. Conclusion: In our study, HIIT and AVG for 12-weeks had no reducing effect on inflammatory markers. Patients with high baseline IL-6 levels had a positive change in CRF during intervention. In order to increase our knowledge regarding association between inflammatory markers and exercise in individuals with schizophrenia, larger studies with more frequent and longer exercise bout duration are warranted.

• Grover, Steven P.; Snir, Omri; Hindberg, Kristian Dalsbø; Englebert, Tatianna M.; Brækkan, Sigrid Kufaas & Morelli, Vania Maris [Show all 12 contributors for this article] (2023). High plasma levels of C1-inhibitor are associated with lower risk of future venous thromboembolism. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. 21(7), p. 1849–1860. doi: 10.1016/j.jtha.2023.03.024. Full text in Research Archive
• Skjeflo, Espen Waage; Evensen, Line Holtet; Jensen, Søren Beck; Latysheva, Nadezhda; Michelsen, Annika Elisabet & Ueland, Thor [Show all 11 contributors for this article] (2023). Complement factors B, D, C3bBbP and risk of future venous thromboembolism. Clinical Immunology. ISSN 1521-6616. 249:109278, p. 1–7. doi: 10.1016/j.clim.2023.109278. Full text in Research Archive
• Farbu, Bjørn Hoftun; Langeland, Halvor; Ueland, Thor; Michelsen, Annika Elisabet; Krüger, Andreas Jørstad & Klepstad, Pål [Show all 7 contributors for this article] (2023). Intestinal injury in cardiac arrest is associated with multiple organ dysfunction: A prospective cohort study. Resuscitation. ISSN 0300-9572. 185. doi: 10.1016/j.resuscitation.2023.109748. Full text in Research Archive
• Osete, Jordi Requena; Akkouh, Ibrahim Ahmed; Ievglevskyi, Oleksandr; Vandenberghe, Matthieu; Reis de Assis, Denis & Ueland, Thor [Show all 14 contributors for this article] (2023). Transcriptional and functional effects of lithium in bipolar disorder iPSC-derived cortical spheroids. Molecular Psychiatry. ISSN 1359-4184. 28, p. 3033–3043. doi: 10.1038/s41380-023-01944-0. Full text in Research Archive
• Tveita, Anders; Murphy, Sarah Louise Mikalsen; Halvorsen, Bente; Dahl, Tuva Børresdatter; Ueland, Thor & SOLIDARITY consortium, NOR- [Show all 7 contributors for this article] (2022). High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in COVID-19. Journal of Infectious Diseases. ISSN 0022-1899. doi: 10.1093/infdis/jiac313.
• Sæther, Linn Sofie; Ueland, Thor; Haatveit, Beathe; Maglanoc, Luigi Angelo; Szabo, Attila & Djurovic, Srdjan [Show all 15 contributors for this article] (2022). Inflammation and cognition in severe mental illness: patterns of covariation and subgroups. Molecular Psychiatry. ISSN 1359-4184. doi: 10.1038/s41380-022-01924-w.
• Fosheim, Ingrid Knutsdotter; Jacobsen, Daniel Pitz; Sugulle, Meryam; Alnæs-Katjavivi, Patji; Fjeldstad, Heidi & Ueland, Thor [Show all 8 contributors for this article] (2022). Serum amyloid A1 and pregnancy zone protein in pregnancy complications and correlation with markers of placental dysfunction. American Journal of Obstetrics & Gynecology MFM (AJOG MFM). ISSN 2589-9333. 5(1). doi: 10.1016/j.ajogmf.2022.100794. Full text in Research Archive
• Nilsen, Dennis W.T.; Røysland, Michelle; Ueland, Thor; Aukrust, Pål; Michelsen, Annika Elisabet & Staines, Harry [Show all 10 contributors for this article] (2022). The Effect of Protease-Activated Receptor-1 (PAR-1) Inhibition on Endothelial-Related Biomarkers in Patients with Coronary Artery Disease. Thrombosis and Haemostasis. ISSN 0340-6245. doi: 10.1055/s-0042-1760256. Full text in Research Archive Show summary

  Abstract Background: Vorapaxar has been shown to reduce cardiovascular mortality in postmyocardial infarction (MI) patients. Pharmacodynamic biomarker research related to protease-activated receptor-1 (PAR-1) inhibition with vorapaxar in humans has short follow-up (FU) duration and is mainly focused on platelets rather than endothelial cells. Aim: This article assesses systemic changes in endothelial-related biomarkers during vorapaxar treatment compared with placebo at 30 days’ FU and beyond, in patients with coronary heart disease. Methods: Local substudy patients in Norway were included consecutively from two randomized controlled trials; post-MI subjects from TRA2P-TIMI 50 and non-ST-segment elevation MI (NSTEMI) patients from TRACER. Aliquots of citrated blood were stored at–80°C. Angiopoietin-2, angiopoietin-like 4, vascular endothelial growth factor, intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, von Willebrand factor, thrombomodulin, and plasminogen activator inhibitor-1 and -2 were measured at 1-month FU and at study completion (median 2.3 years for pooled patients). Results: A total of 265 consecutive patients (age median 62.0, males 83%) were included. Biomarkers were available at both FUs in 221 subjects. In the total population, angiopoietin-2 increased in patients on vorapaxar as compared with placebo at 1-month FU (p ¼ 0.034). Angiopoietin-like 4 increased (p ¼ 0.028) and plasminogen activator inhibitor-2 decreased (p ¼ 0.025) in favor of vorapaxar at final FU. In postMI subjects, a short-term increase in E-selectin favoring vorapaxar was observed, p ¼ 0.029. Also, a short-term increase in von Willebrand factor (p ¼ 0.032) favoring vorapaxar was noted in NSTEMI patients. Conclusion: Significant endothelial biomarker changes during PAR-1 inhibition were observed in post-MI and NSTEMI patients.

• Seim, Bjørn Edvard; Holt, Margrethe Flesvig; Ratajska, Aleksandra; Michelsen, Annika Elisabet; Ringseth, Monica Myklebust & Halvorsen, Bente [Show all 14 contributors for this article] (2022). Markers of extracellular matrix remodeling and systemic inflammation in patients with heritable thoracic aortic diseases. Frontiers in Cardiovascular Medicine. ISSN 2297-055X. 9, p. 1–9. doi: 10.3389/fcvm.2022.1073069. Full text in Research Archive
• Sæther, Linn Sofie; Ueland, Thor; Haatveit, Beathe; Maglanoc, Luigi; Szabo, Attila & Djurovic, Srdjan [Show all 14 contributors for this article] (2022). Inflammation and cognition in severe mental illness: patterns of covariation and subgroups. Molecular Psychiatry. ISSN 1359-4184. 8, p. 1284–1292. doi: 10.1038/s41380-022-01924-w. Full text in Research Archive
• Stø, Kristine; Valeur, Jørgen; Ueland, Thor; Malmstrøm, Gunn Helen; Bjerkeli, Vigdis & Trøseid, Marius [Show all 12 contributors for this article] (2022). Fecal level of butyric acid, a microbiome-derived metabolite, is increased in patients with severe carotid atherosclerosis. Scientific Reports. ISSN 2045-2322. 12(1), p. 1–9. doi: 10.1038/s41598-022-26759-x. Full text in Research Archive
• Rixon, Chloe Louise; Andreassen, Kristine; Shen, Xin; Murugan Erusappan, Pugazendhi; Almaas, Vibeke Marie & Palmero, Sheryl [Show all 14 contributors for this article] (2022). Lumican accumulates with fibrillar collagen in fibrosis in hypertrophic cardiomyopathy. ESC Heart Failure. ISSN 2055-5822. doi: 10.1002/ehf2.14234. Full text in Research Archive
• Jensen, Søren Beck; Sheikh, Mashhood Ahmed; Akkouh, Ibrahim Ahmed; Szabo, Attila; O'Connell, Kevin Sean & Lekva, Tove [Show all 23 contributors for this article] (2022). Elevated Systemic Levels of Markers Reflecting Intestinal Barrier Dysfunction and Inflammasome Activation Are Correlated in Severe Mental Illness. Schizophrenia Bulletin. ISSN 0586-7614. 49(3), p. 635–645. doi: 10.1093/schbul/sbac191.
• Didriksen, Henriette; Molberg, Øyvind; Mehta, Adi; Jordan, Suzana; Palchevskiy, Vyacheslav & Fretheim, Håvard Halland [Show all 16 contributors for this article] (2022). Target organ expression and biomarker characterization of chemokine CCL21 in systemic sclerosis associated pulmonary arterial hypertension. Frontiers in Immunology. ISSN 1664-3224. 13. doi: 10.3389/fimmu.2022.991743. Full text in Research Archive
• Granerud, Beathe Kiland; Ueland, Thor; Lind, Andreas; Søraas, Arne Vasli; Fevang, Børre & Steffensen, Anne Katrine [Show all 14 contributors for this article] (2022). Omicron Variant Generates a Higher and More Sustained Viral Load in Nasopharynx and Saliva Than the Delta Variant of SARS-CoV-2. Viruses. ISSN 1999-4915. 14(11). doi: 10.3390/v14112420. Full text in Research Archive Show summary

  The Omicron variant of SARS-CoV-2 spreads more easily than earlier variants, possibly as a result of a higher viral load in the upper respiratory tract and oral cavity. Hence, we investigated whether the Omicron variant generates a higher viral load than that of the Delta variant in saliva and nasopharynx. Both specimens were collected from 52 Omicron and 17 Delta cases at two time points one week apart and analyzed by qRT-PCR. Viral load was measured as 10 log RNA genome copies per 1000 human cells according to the WHO reference standard. We found that Omicron cases carried a higher viral load and had more sustained viral shedding compared to the Delta cases, especially in the nasopharynx.

• Lekva, Tove; Ueland, Thor; Halvorsen, Bente; Murphy, Sarah Louise Mikalsen; Dyrhol-Riise, Anne Ma & Tveita, Anders Aune [Show all 14 contributors for this article] (2022). Markers of cellular senescence is associated with persistent pulmonary pathology after COVID-19 infection. Infectious Diseases. ISSN 2374-4235. 54(12), p. 918–923. doi: 10.1080/23744235.2022.2113135. Full text in Research Archive Show summary

  Background The lungs are the organ most likely to sustain serious injury from coronavirus disease 2019 (COVID-19). However, the mechanisms for long-term complications are not clear. Patients with severe COVID-19 have shorter telomere lengths and higher levels of cellular senescence, and we hypothesized that circulating levels of the telomere-associated senescence markers chitotriosidase, β-galactosidase, cathelicidin antimicrobial peptide and stathmin 1 (STMN1) were elevated in hospitalized COVID-19 patients compared to controls and could be associated with pulmonary sequelae following hospitalization. Methods Ninety-seven hospitalized patients with COVID-19 who underwent assessment for pulmonary sequelae at three-month follow-up were included in the study. β-Galactosidase and chitotriosidase were analysed by fluorescence; stathmin 1 and cathelicidin antimicrobial peptide were analysed by enzyme immuno-assay in plasma samples from the acute phase and after three-months. In addition, the classical senescence markers cyclin-dependent kinase inhibitor 1A and 2A were analysed by enzyme immuno-assay in peripheral blood mononuclear cell lysate after three months. Results We found elevated plasma levels of the senescence markers chitotriosidase and stathmin 1 in patients three months after hospitalization with COVID-19, and these markers in addition to protein levels of cyclin-dependent kinase inhibitor 2A in cell lysate, were associated with pulmonary pathology. The elevated levels of these markers seem to reflect both age-dependent (chitotriosidase) and age-independent (stathmin 1, cyclin-dependent kinase inhibitor 2A) processes. Conclusions We suggest that accelerated ageing or senescence could be important for long-term pulmonary complications of COVID-19, and our findings may be relevant for future research exploring the pathophysiology and management of these patients.

• Lee-Ødegård, Sindre; Ueland, Thor; Thorsby, Per Medbøe; Aukrust, Pål; Michelsen, Annika Elisabet & Halvorsen, Bente [Show all 8 contributors for this article] (2022). Fetuin-A mediates the difference in adipose tissue insulin resistance between young adult pakistani and norwegian patients with type 2 diabetes. BMC Endocrine Disorders. ISSN 1472-6823. 22. doi: 10.1186/s12902-022-01127-y. Full text in Research Archive Show summary

  Background South-Asian immigrants to Western countries have a high prevalence of type 2 diabetes mellitus (T2DM) and increased adipose tissue insulin resistance (AT-IR), as compared to their Western counterparts. Fetuin-A is a hepatokine known to influence AT-IR. Aim Can plasma fetuin-A concentrations explain an ethnic difference in adipose tissue insulin resistance? Methods We performed a two-step euglycemic-hyperinsulinaemic clamp and measured plasma concentrations of fetuin-A and non-esterified fatty acids (NEFA), in 18 Pakistani and 21 Norwegians with T2DM (age 29–45y) in Norway. AT-IR was calculated as NEFA-suppression during the clamp. The adipokines/cytokines leptin, adiponectin, visfatin, PTX3, IL-1β, INF-γ, and IL-4 were measured in fasting plasma. Liver fat was estimated by CT-scans. Results Despite a lower BMI, Pakistani patients displayed higher AT-IR than Norwegians. NEFA-suppression during clamp was lower in Pakistani than Norwegians (mean=-20.6%, 95%CI=[-40.8, -0.01] and p = 0.046). Plasma fetuin-A concentration was higher in Pakistani than Norwegians (43.4 ng/mL[12.7,74.0], p = 0.007) and correlated negatively to %NEFA-suppression during clamp (rho=-0.39, p = 0.039). Plasma fetuin-A concentration explained 22% of the ethnic difference in NEFA-suppression during the clamp. Pakistani patients exhibited higher plasma leptin and lower PTX3 levels than Norwegian, and plasma visfatin correlated positively to plasma fetuin-A levels in the Pakistani patients. We observed no correlation between plasma fetuin-A and liver fat, but fetuin-A correlated negatively with plasma IL-1β, INF-γ, and IL-4 concentrations. Plasma IL-4 concentration was lower in Pakistani than in Norwegian patients. Conclusion Fetuin-A may contribute to explain the discrepancy in T2DM prevalence between Pakistani and Norwegians patients by influencing AT-IR.

• Gelpi, M; Vestad, Beate; Raju, Sajan; Hansen, Simen Hyll; Høgh, J & Midttun, Øivind [Show all 13 contributors for this article] (2022). Association of the Kynurenine Pathway of Tryptophan Metabolism with Human Immunodeficiency Virus-Related Gut Microbiota Alterations and Visceral Adipose Tissue Accumulation. Journal of Infectious Diseases. ISSN 0022-1899. 225(11), p. 1948–1954. doi: 10.1093/infdis/jiac018.
• Huse, Camilla; Anstensrud, Anne Kristine; Michelsen, Annika Elisabet; Ueland, Thor; Broch, Kaspar & Woxholt, Sindre [Show all 29 contributors for this article] (2022). Interleukin-6 inhibition in ST-elevation myocardial infarction: Immune cell profile in the randomised ASSAIL-MI trial. EBioMedicine. ISSN 2352-3964. 80. doi: 10.1016/j.ebiom.2022.104013. Full text in Research Archive
• Vergaro, Giuseppe; Gentile, Francesco; Aimo, Alberto; Januzzi, James L.; Richards, A. Mark & Lam, Carolyn S.P. [Show all 39 contributors for this article] (2022). Circulating levels and prognostic cut-offs of sST2, hs-cTnT, and NT-proBNP in women vs. men with chronic heart failure. ESC Heart Failure. ISSN 2055-5822. 9(4), p. 2084–2095. doi: 10.1002/ehf2.13883. Full text in Research Archive
• Søraas, Arne Vasli; Grødeland, Gunnveig; Granerud, Beathe Kiland; Ueland, Thor; Lind, Andreas & Fevang, Børre [Show all 32 contributors for this article] (2022). Breakthrough infections with the omicron and delta variants of SARS-CoV-2 result in similar re-activation of vaccine-induced immunity. Frontiers in Immunology. ISSN 1664-3224. 13:964525, p. 1–12. doi: 10.3389/fimmu.2022.964525. Full text in Research Archive Show summary

  Background: Results showing that sera from double vaccinated individuals have minimal neutralizing activity against Omicron have been interpreted as indicating the need for a third vaccine dose for protection. However, there is little information about early immune responses to Omicron infection in double vaccinated individuals. Methods: We measured inflammatory mediators, antibodies to the SARS-CoV-2 spike and nucleocapsid proteins, and spike peptide-induced release of interferon gamma in whole blood in 51 double-vaccinated individuals infected with Omicron, in 14 infected with Delta, and in 18 healthy controls. The median time points for the first and second samples were 7 and 14 days after symptom onset, respectively. Findings: Infection with Omicron or Delta led to a rapid and similar increase in antibodies to the receptor-binding domain (RBD) of Omicron protein and spike peptide-induced interferon gamma in whole blood. Both the Omicron- and the Delta-infected patients had a mild and transient increase in inflammatory parameters. Interpretation: The results suggest that two vaccine doses are sufficient to mount a rapid and potent immune response upon infection in healthy individuals of with the Omicron variant.

• Sheikh, Mashhood Ahmed; O'Connell, Kevin Sean; Lekva, Tove; Szabo, Attila; Akkouh, Ibrahim Ahmed & Osete, Jordi Requena [Show all 31 contributors for this article] (2022). Systemic cell adhesion molecules in severe mental illness: Potential role of intercellular CAM-1 in linking peripheral and neuroinflammation. Biological Psychiatry. ISSN 0006-3223. 93, p. 187–196. doi: 10.1016/j.biopsych.2022.06.029. Full text in Research Archive Show summary

  Background Cell adhesion molecules (CAMs) orchestrate leukocyte trafficking and could link peripheral and neuroinflammation in patients with severe mental illness (SMI), by promoting inflammatory and immune-mediated responses and mediating signals across blood-brain barrier. We hypothesized that CAMs would be dysregulated in SMI and evaluated plasma levels of different vascular and neural CAMs. Dysregulated CAMs in plasma were further evaluated in vivo in leukocytes and brain tissue and in vitro in induced pluripotent stem cells. Methods We compared plasma soluble levels of different vascular (VCAM-1, ICAM-1, P-SEL) and neural (JAM-A, NCAD) CAMs in circulating leukocytes in a large SMI sample of schizophrenia (SCZ) spectrum disorder (n = 895) and affective disorder (n = 737) and healthy control participants (n = 1070) controlling for age, sex, body mass index, C-reactive protein, and freezer storage time. We also evaluated messenger RNA expression of ICAM1 and related genes encoding ICAM-1 receptors in leukocytes using microarray (n = 842) and in available RNA sequencing data from the CommonMind Consortium (CMC) in postmortem samples from the dorsolateral prefrontal cortex (n = 474). The regulation of soluble ICAM-1 in induced pluripotent stem cell–derived neurons and astrocytes was assessed in patients with SCZ and healthy control participants (n = 8 of each). Results Our major findings were 1) increased soluble ICAM-1 in patients with SMI compared with healthy control participants; 2) increased ITGB2 messenger RNA, encoding the beta chain of the ICAM-1 receptor, in circulating leukocytes from patients with SMI and increased prefrontal cortex messenger RNA expression of ICAM1 in SCZ; and 3) enhanced soluble ICAM-1 release in induced pluripotent stem cell–derived neurons from patients with SCZ. Conclusions Our results support a systemic and cerebral dysregulation of soluble ICAM-1 expression in SMI and especially in patients with SCZ.

• Fraz, Mai Sasaki Aanensen; Michelsen, Annika Elisabet; Moe, Natasha; Aaløkken, Trond Mogens; Macpherson, Magnhild Eide & Nordøy, Ingvild [Show all 12 contributors for this article] (2022). Raised Serum Markers of T Cell Activation and Exhaustion in Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency. Journal of Clinical Immunology. ISSN 0271-9142. p. 1–11. doi: 10.1007/s10875-022-01318-1. Full text in Research Archive
• Englund, Kristine Victoria Brautaset; Østby, Carol Margaret; Broch, Kaspar; Ueland, Thor; Aukrust, Pål & Gude, Einar [Show all 8 contributors for this article] (2022). Iron homeostasis in heart transplant recipients randomized to ferric derisomaltose or placebo. Clinical Transplantation. ISSN 0902-0063. 36(7). doi: 10.1111/ctr.14695. Full text in Research Archive
• Tveita, Anders Aune; Murphy, Sarah Louise Mikalsen; Holter, Jan Cato; Kildal, Anders Benjamin; Michelsen, Annika Elisabet & Lerum, Tøri Vigeland [Show all 28 contributors for this article] (2022). High Circulating Levels of the Homeostatic Chemokines CCL19 and CCL21 Predict Mortality and Disease Severity in COVID-19. Journal of Infectious Diseases. ISSN 0022-1899. 226(12), p. 2150–2160. doi: 10.1093/infdis/jiac313. Full text in Research Archive
• Trøseid, Marius; Dahl, Tuva Børresdatter; Holter, Jan Cato; Kildal, Anders Benjamin; Murphy, Sarah Louise Mikalsen & Yang, Kuan [Show all 28 contributors for this article] (2022). Persistent T-cell exhaustion in relation to prolonged pulmonary pathology and death after severe COVID-19: Results from two Norwegian cohort studies. Journal of Internal Medicine. ISSN 0954-6820. 292(5), p. 816–828. doi: 10.1111/joim.13549. Full text in Research Archive
• Ormerod, Monica Bettina E. Greenwood; Ueland, Thor; Werner, Maren Caroline Frogner; Hjell, Gabriela; Rødevand, Linn Nilsen & Sæther, Linn Sofie [Show all 14 contributors for this article] (2022). Composite immune marker scores associated with severe mental disorders and illness course. Brain, Behavior, and Immunity - Health (BBI - Health). ISSN 2666-3546. 24. doi: 10.1016/j.bbih.2022.100483. Full text in Research Archive
• Berg, Janna; Halvorsen, Ann Rita; Bengtson, May-Bente; Lindberg, Morten; Halvorsen, Bente & Aukrust, Pål [Show all 8 contributors for this article] (2022). Circulating T Cell Activation and Exhaustion Markers Are Associated With Radiation Pneumonitis and Poor Survival in Non-Small-Cell Lung Cancer. Frontiers in Immunology. ISSN 1664-3224. 13. doi: 10.3389/fimmu.2022.875152. Full text in Research Archive Show summary

  Persistent inflammation and immune activation in the lungs are associated with adverse outcomes such as radiation pneumonitis (RP) and poor survival in non-small-cell lung cancer (NSCLC) patients. However, it is unknown how this is reflected by leukocyte activation markers in serum. Objective: The aim was to evaluate the serum levels of activation of different leukocyte subsets and to examine those in relation to the pathogenesis of RP and survival in NSCLC. Methods: We analyzed the serum levels of MPO, sCD25, sTIM-3, sPD-L1, sCD14, sCD163, CCL19 and CCL21 in 66 inoperable NSCLC patients with stage IA-IIIA disease. The patients were treated with stereotactic body radiation therapy (SBRT) or concurrent chemoradiation therapy (CCRT), followed by regular blood sampling for 12 months after treatment and for 5 years for survival. Results: Nineteen (29%) patients developed RP, which occurred more frequently and earlier in patients receiving CCRT than in those receiving SBRT. Increases in sCD25, sTIM-3 and CCL21 levels were observed at the last 6 months of follow-up in patients who had RP after SBRT. Patients who had RP after CCRT had higher sTIM-3 levels during the first 3 months of follow-up. Baseline sCD25 was independently associated with both 2- and 5-year mortality outcomes, while baseline sTIM-3 was independently associated with 2-year mortality. Conclusion: We showed that T cell activation and exhaustion markers such as sCD25 and sTIM-3 are enhanced in patients developing RP and are associated with poor survival in NSCLC.

• Andersen, Thomas; Ueland, Thor; Aukrust, Pål; Nilsen, Dennis W.T.; Grundt, Magnea Heidi Jonsdottir & Staines, Harry [Show all 7 contributors for this article] (2022). Podocan and Adverse Clinical Outcome in Patients Admitted With Suspected Acute Coronary Syndromes. Frontiers in Cardiovascular Medicine. ISSN 2297-055X. 9, p. 1–9. doi: 10.3389/fcvm.2022.867944. Full text in Research Archive Show summary

  Background: Markers of bone and extracellular matrix (ECM) remodeling may be associated with adverse outcomes in atherosclerotic cardiovascular disease. Podocan is a newly discovered ECM glycoprotein, previously not studied in a chest pain population. We wanted to study the association between Podocan levels on admission and the risk of adverse outcomes in a chest pain population with suspected acute coronary syndromes. Methods: A total of 815 patients from the Risk markers in Acute Coronary Syndrome (RACS) trial with suspected coronary chest pain were followed for 7 years. Blood samples were taken immediately after inclusion and stored in the biobank. Associations between Podocan and endpoints were assessed with Cox proportional hazards analyses. Results: The median admission level of Podocan was 0.674 ng/ml (0.566–0.908 ng/ml). No significant association was found between Podocan quartile levels and all-cause death, neither at 1 year nor 2- or 7-years follow-up (p > 0.05 for all). Furthermore, no significant association could be shown between Podocan and cardiac death, myocardial infarction (MI), stroke, or the composites of all-cause death/MI/stroke or cardiac death/MI/stroke (p > 0.05 for all). Similarly, in a subgroup of patients with Troponin T-positive (n = 432) there was no significant association between Podocan and any of the outcome measures (p > 0.05 for all endpoints and points in time). Conclusion: Podocan, a novel ECM biomarker, is not associated with all-cause mortality or other major cardiovascular adverse events in patients admitted with acute chest pain suspected to be of coronary origin.

• Ueland, Thor; Sørvoll, Ingvild Hausberg; Mørtberg, Trude Victoria; Dahl, Tuva Børresdatter; Lerum, Tøri Vigeland & Michelsen, Annika Elisabet [Show all 16 contributors for this article] (2022). Anti-PF4/polyanion antibodies in COVID-19 patients are associated with disease severity and pulmonary pathology. Platelets. ISSN 0953-7104. 33(4), p. 640–644. doi: 10.1080/09537104.2022.2042238. Full text in Research Archive
• Jensen, Søren Beck; Latysheva, Nadezhda; Hindberg, Kristian & Ueland, Thor (2022). Plasma lipopolysaccharide-binding protein is a biomarker for future venous thromboembolism: Results from discovery and validation studies. Journal of Internal Medicine. ISSN 0954-6820. p. 1–13. doi: 10.1111/joim.13502. Full text in Research Archive
• Hjell, Gabriela; Szabo, Attila; Mørch-Johnsen, Lynn Egeland; Holst, Rene; Tesli, Natalia & Bell, Christina [Show all 18 contributors for this article] (2022). Interleukin-18 signaling system links to agitation in severe mental disorders. Psychoneuroendocrinology. ISSN 0306-4530. 140:105721, p. 1–8. doi: 10.1016/j.psyneuen.2022.105721. Full text in Research Archive Show summary

  Objective Agitation is a challenging clinical feature in severe mental disorders, but its biological correlates are largely unknown. Inflammasome-related abnormalities have been linked to severe mental disorders and implicated in animal models of agitation. We investigated if levels of circulating inflammasome-related immune markers were associated with agitation in severe mental disorders. Methods Individuals with a psychotic or affective disorder (N = 660) underwent blood sampling and clinical characterization. Plasma levels of interleukin (IL)‐18, IL-18 binding protein (IL-18BP), IL-18 receptor 1 (IL-18R1), IL-18 receptor accessory protein (IL-18RAP), and IL-1 receptor antagonist (IL-1RA) were measured. Agitation levels were estimated with the Positive and Negative Syndrome Scale Excited Component. Multiple linear- and logistic regression were used to investigate the associations between agitation and the immune markers, while controlling for confounders. The influence of psychotic and affective symptoms was assessed in follow-up analyses. Results Agitation was positively associated with IL-18BP (β = 0.13, t = 3.41, p = 0.0007) after controlling for multiple confounders, including BMI, smoking, medication, and substance use. Adjustment for psychotic, manic, and depressive symptoms did not affect the results. There were no significant associations between agitation and the other investigated immune markers (IL-1RA (β = 0.06, t = 1.27, p = 0.20), IL-18 (β = 0.05, t = 1.25, p = 0.21), IL-18R1 (β = 0.04, t = 1.01, p = 0.31), IL-18RAP (odds ratio = 0.96, p = 0.30)). In a subsample (N = 463), we also adjusted for cortisol levels, which yielded unaltered results. Conclusion Our findings add to the accumulating evidence of immune system disturbances in severe mental disorders and suggest the IL-18 system as a part of the biological correlate of agitation independent of affective and psychotic symptoms.

• Werner, Maren Caroline Frogner; Wirgenes, Katrine Verena; Shadrin, Alexey; Lunding, Synve Hoffart; Rødevand, Linn & Hjell, Gabriela [Show all 15 contributors for this article] (2022). Immune marker levels in severe mental disorders: associations with polygenic risk scores of related mental phenotypes and psoriasis. Translational Psychiatry. ISSN 2158-3188. 12(1). doi: 10.1038/s41398-022-01811-6. Full text in Research Archive Show summary

  Several lines of evidence implicate immune abnormalities in the pathophysiology of severe mental disorders (SMD) and comorbid mental disorders. Here, we use the data from genome-wide association studies (GWAS) of autoimmune diseases and mental phenotypes associated with SMD to disentangle genetic susceptibilities of immune abnormalities in SMD. We included 1004 patients with SMD and 947 healthy controls (HC) and measured plasma levels of IL-1Ra, sIL-2R, gp130, sTNFR-1, IL-18, APRIL, and ICAM-1. Polygenic risk scores (PRS) of six autoimmune disorders, CRP, and 10 SMD-related mental phenotypes were calculated from GWAS. General linear models were applied to assess the association of PRS with immune marker abnormalities. We found negative associations between PRS of educational attainment and IL-1Ra (P = 0.01) and IL-18 (P = 0.01). There were nominal positive associations between PRS of psoriasis and sgp130 (P = 0.02) and PRS of anxiety and IL-18 (P = 0.03), and nominal negative associations between PRS of anxiety and sIL-2R (P = 0.02) and PRS of educational attainment and sIL-2R (P = 0.03). Associations explained minor amounts of the immune marker plasma-level difference between SMD and HC. Different PRS and immune marker associations in the SMD group compared to HC were shown for PRS of extraversion and IL-1Ra ([interaction effect (IE), P = 0.002), and nominally for PRS of openness and IL-1Ra (IE, P = 0.02) and sTNFR-1 (IE, P = 0.04). Our findings indicate polygenic susceptibilities to immune abnormalities in SMD involving genetic overlap with SMD-related mental phenotypes and psoriasis. Associations might suggest immune genetic factors of SMD subgroups characterized by autoimmune or specific mental features.

• Tønnessen, Theis Christian; Melleby, Arne Olav; Hauge-Iversen, Ida Marie; Espe, Emil Knut Stenersen; Ahmed, Muhammad Shakil & Ueland, Thor [Show all 12 contributors for this article] (2022). Impact of delayed type hypersensitivity arthritis on development of heart failure by aortic constriction in mice. PLOS ONE. ISSN 1932-6203. 17(1). doi: 10.1371/journal.pone.0262821. Full text in Research Archive Show summary

  Aims Patients with rheumatoid arthritis (RA) have increased risk of heart failure (HF). The mechanisms and cardiac prerequisites explaining this association remain unresolved. In this study, we sought to determine the potential cardiac impact of an experimental model of RA in mice subjected to HF by constriction of the ascending aorta. Methods Aorta was constricted via thoracotomy and placement of o-rings with inner diameter 0.55 mm or 0.66 mm, or sham operated. RA-like phenotype was instigated by delayed-type hypersensitivity arthritis (DTHA) two weeks after surgery and re-iterated after additional 18 days. Cardiac magnetic resonance imaging (MRI) was performed before surgery and at successive time points throughout the study. Six weeks after surgery the mice were euthanized, blood and tissue were collected, organ weights were documented, and expression levels of cardiac foetal genes were analysed. In a supplemental study, DTHA-mice were euthanized throughout 14 days after induction of arthritis, and blood was analysed for important markers and mediators of RA (SAP, TNF-α and IL-6). In order to put the latter findings into clinical context, the same molecules were analysed in serum from untreated RA patients and compared to healthy controls. Results Significant elevations of inflammatory markers were found in both patient- and murine blood. Furthermore, the DTHA model appeared clinically relevant when compared to the inflammatory responses observed in three prespecified RA severity disease states. Two distinct trajectories of cardiac dysfunction and HF development were found using the two o-ring sizes. These differences were consistent by both MRI, organ weights and cardiac foetal gene expression levels. Still, no difference within the HF groups, nor within the sham groups, could be found when DTHA was induced. Conclusion DTHA mediated systemic inflammation did not cause, nor modify HF caused by aortic constriction. This indicates other prerequisites for RA-induced cardiac dysfunction.

• Oppen, Kjersti; Ueland, Thor; Michelsen, Annika Elisabet; Aukrust, Pål; Steinsvik, Trude & Skadberg, Øyvind [Show all 11 contributors for this article] (2022). Hepcidin predicts 5-year mortality after community-acquired pneumonia. Infectious Diseases. ISSN 2374-4235. 54(6), p. 403–409. doi: 10.1080/23744235.2021.2022194. Full text in Research Archive
• Simeone, Paola; Tripaldi, Romina; Michelsen, Annika Elisabet; Ueland, Thor; Liani, Rossella & Ciotti, Sonia [Show all 14 contributors for this article] (2022). Effects of liraglutide vs. lifestyle changes on soluble suppression of tumorigenesis-2 (sST2) and galectin-3 in obese subjects with prediabetes or type 2 diabetes after comparable weight loss. Cardiovascular Diabetology. ISSN 1475-2840. 21. doi: 10.1186/s12933-022-01469-w. Full text in Research Archive
• Vergaro, Giuseppe; Aimo, Alberto; Januzzi, James L.; Richards, A Mark; Lam, Carolyn S P & Latini, Roberto [Show all 28 contributors for this article] (2022). Cardiac biomarkers retain prognostic significance in patients with heart failure and chronic obstructive pulmonary disease. Journal of Cardiovascular Medicine. ISSN 1558-2027. 23(1), p. 28–36. doi: 10.2459/JCM.0000000000001281.
• Werner, Maren Caroline Frogner; Wirgenes, Katrine Verena; Shadrin, Alexey; Lunding, Synve Hoffart; Rødevand, Linn & Hjell, Gabriela [Show all 15 contributors for this article] (2022). Limited association between infections, autoimmune disease and genetic risk and immune activation in severe mental disorders. Progress in Neuro-psychopharmacology and Biological Psychiatry. ISSN 0278-5846. 116. doi: 10.1016/j.pnpbp.2022.110511. Full text in Research Archive Show summary

  Background Low-grade inflammation may be part of the underlying mechanism of schizophrenia and bipolar disorder. We investigated if genetic susceptibility, infections or autoimmunity could explain the immune activation. Methods Seven immune markers were selected based on indicated associations to severe mental disorders (IL-1Ra, sIL-2R, IL-18, sgp130, sTNFR-1, APRIL, ICAM-1) and measured in plasma of patients with schizophrenia (SCZ, N = 732) and bipolar spectrum disorders (BD, N = 460) and healthy controls (HC, N = 938). Information on rate of infections and autoimmune diseases were obtained from Norwegian national health registries for a twelve-year period. Polygenic risk scores (PRS) of SCZ and BD were calculated from genome-wide association studies. Analysis of covariance were used to test effects of infection rate, autoimmune disease and PRS on differences in immune markers between patients and HC. Results Infection rate differed between all groups (BD > HC > SCZ, all p < 0.001) whereas autoimmune disease was more frequent in BD compared to SCZ (p = 0.004) and HC (p = 0.003). sIL-2R was positively associated with autoimmune disease (p = 0.001) and negatively associated with PRS of SCZ (p = 0.006) across SCZ and HC; however, associations represented only small changes in the difference of sIL-2R levels between SCZ and HC. Conclusion There were few significant associations between rate of infections, autoimmune disease or PRS and altered immune markers in SCZ and BD, and the detected associations represented only small changes in the immune aberrations. The findings suggest that most of the low-grade inflammation in SCZ and BD is explained by other factors than the underlying PRS, autoimmunity and infection rates.

• Frischmuth, Tobias; Hindberg, Kristian; Aukrust, Pål; Ueland, Thor; Brækkan, Sigrid Kufaas & Hansen, John Bjarne [Show all 7 contributors for this article] (2022). Elevated plasma levels of plasminogen activator inhibitor-1 are associated with risk of future incident venous thromboembolism. Journal of Thrombosis and Haemostasis. ISSN 1538-7933. p. 1–9. doi: 10.1111/jth.15701. Full text in Research Archive
• Tennøe, Anders; Murbræch, Klaus; Didriksen, Henriette; Ueland, Thor; Palchevskiy, Vyacheslav & Weigt, Stephen S. [Show all 14 contributors for this article] (2022). Serum markers of cardiac complications in a systemic sclerosis cohort. Scientific Reports. ISSN 2045-2322. 12(4661 ). doi: 10.1038/s41598-022-08815-8. Full text in Research Archive
• Heldal, Torbjørn Fossum; Åsberg, Anders; Ueland, Thor; Reisæter, Anna Varberg; Pischke, Søren Erik & Mollnes, Tom Eirik [Show all 10 contributors for this article] (2022). Inflammation in the early phase after kidney transplantation is associated with increased long-term all-cause mortality. American Journal of Transplantation. ISSN 1600-6135. 22, p. 2016–2027. doi: 10.1111/ajt.17047. Full text in Research Archive Show summary

  In the general population low-grade inflammation has been established as a risk factor for all-cause mortality. We hypothesized that an inflammatory milieu beyond the time of recovery from the surgical trauma could be associated with increased long-term mortality in kidney transplant recipients (KTRs). This cohort study included 1044 KTRs. Median follow-up time post-engraftment was 10.3 years. Inflammation was assessed 10 weeks after transplantation by different composite inflammation scores based on 21 biomarkers. We constructed an overall inflammation score and five pathway-specific inflammation scores (fibrogenesis, vascular inflammation, metabolic inflammation, growth/angiogenesis, leukocyte activation). Mortality was assessed with Cox regression models adjusted for traditional risk factors. A total of 312 (29.9%) patients died during the follow-up period. Hazard ratio (HR) for death was 4.71 (95% CI:2.85-7.81, p

• Vestad, Beate; Ueland, Thor; Lerum, Tøri Vigeland; Dahl, Tuva Børresdatter; Holm, Kristian & Barratt-Due, Andreas [Show all 37 contributors for this article] (2022). Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterations. Journal of Internal Medicine. ISSN 0954-6820. 291(6), p. 801–812. doi: 10.1111/joim.13458. Full text in Research Archive Show summary

  Background: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal (GI) tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long-term respiratory dysfunction remains unknown. Methods: Plasma was collected during hospital admission and after three months from the NOR-Solidarity trial (n = 181) and analysed for markers of gut barrier dysfunction and inflammation. At the three-month follow-up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DLCO ). Rectal swabs for gut microbiota analyses were collected (n = 97) and analysed by sequencing the 16S rRNA gene. Results: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO below the lower limit of normal three months after hospitalisation. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalisation, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2 /fiO2 -(P/F ratio)

• Vergaro, Giuseppe; Gentile, Francesco; Meems, Laura M.G.; Aimo, Alberto; Januzzi, James L. & Richards, A. Mark [Show all 39 contributors for this article] (2021). NT-proBNP for Risk Prediction in Heart Failure: Identification of Optimal Cutoffs Across Body Mass Index Categories. JACC. Heart failure. ISSN 2213-1779. 9(9), p. 653–663. doi: 10.1016/j.jchf.2021.05.014.
• Holt, Margrethe Flesvig; Michelsen, Annika Elisabet; Shahini, Negar; Bjørkelund, Elisabeth; Bendz, Christina & Massey, Richard J [Show all 15 contributors for this article] (2021). The Alternative Complement Pathway Is Activated Without a Corresponding Terminal Pathway Activation in Patients With Heart Failure. Frontiers in Immunology. ISSN 1664-3224. 12. doi: 10.3389/fimmu.2021.800978. Full text in Research Archive
• Fevang, Børre; Wyller, Vegard Bruun Bratholm; Mollnes, Tom Eirik; Pedersen, Maria; Asprusten, Tarjei Tørre & Michelsen, Annika Elisabet [Show all 8 contributors for this article] (2021). Lasting Immunological Imprint of Primary Epstein-Barr Virus Infection With Associations to Chronic Low-Grade Inflammation and Fatigue. Frontiers in Immunology. ISSN 1664-3224. 12. doi: 10.3389/fimmu.2021.715102. Full text in Research Archive
• Marcks, Nick; Aimo, Alberto; Januzzi, James L.; Vergaro, Giuseppe; Clerico, Aldo & Latini, Roberto [Show all 27 contributors for this article] (2021). Re-appraisal of the obesity paradox in heart failure: a meta-analysis of individual data. Clinical Research in Cardiology. ISSN 1861-0684. 110(8), p. 1280–1291. doi: 10.1007/s00392-021-01822-1. Full text in Research Archive
• Kåsine, Trine; Riise, Anne Margarita Dyrhol; Barratt-Due, Andreas; Kildal, Anders Benjamin; Olsen, Inge Christoffer & Nezvalova-Henriksen, Katerina [Show all 39 contributors for this article] (2021). Neutrophil count predicts outcome in hospitalized COVID-19 patients. Results from the NOR-Solidarity trial. Journal of Internal Medicine. ISSN 0954-6820. 291(2), p. 241–243. doi: 10.1111/joim.13377. Show summary

  Despite numerous studies on SARS-CoV-2-induced inflammation, we still lack markers for rapid disease progression with admission to intensive care unit (ICU) or respiratory failure(RF). Few studies have evaluated the prognostic value of routine diagnostic repertoire available at most hospitals. The NOR-Solidarity trial is an independent add-on study to the WHO Solidarity trial, evaluating hydroxychloroquine (HCQ)and remdesivir compared to standard of care in hospitalized COVID-19 patients [1]. We explored whether standard biomarkers in peripheral blood could give information on ICU admission and RFin hospitalized COVID-19 patients.

• Langeland, Halvor Johannes Breivik; Damås, Jan Kristian; Mollnes, Tom Eirik; Ludviksen, Judith K; Ueland, Thor & Michelsen, Annika Elisabet [Show all 11 contributors for this article] (2021). The inflammatory response is related to circulatory failure after out-of-hospital cardiac arrest: A prospective cohort study. Resuscitation. ISSN 0300-9572. 170, p. 115–125. doi: 10.1016/j.resuscitation.2021.11.026. Full text in Research Archive Show summary

  Background: Whole body ischemia and reperfusion injury after cardiac arrest leads to the massive inflammation clinically manifested in the post-cardiac arrest syndrome. Previous studies on the inflammatory effect on circulatory failure after cardiac arrest have either investigated a selected patient group or a limited part of the inflammatory mechanisms. We examined the association between cardiac arrest characteristics and inflammatory biomarkers, and between inflammatory biomarkers and circulatory failure after cardiac arrest, in an unselected patient cohort. Methods: This was a prospective study of 50 consecutive patients with out-of-hospital cardiac arrest. Circulation was invasively monitored from admission until day five, whereas inflammatory biomarkers, i.e. complement activation, cytokines and endothelial injury, were measured daily. We identified predictors for an increased inflammatory response, and associations between the inflammatory response and circulatory failure. Results: We found a marked and broad inflammatory response in patients after cardiac arrest, which was associated with clinical outcome. Long time to return of spontaneous circulation and high lactate level at admission were associated with increased complement activation (TCC and C3bc), pro-inflammatory cytokines (IL-6, IL-8) and endothelial injury (syndecan-1) at admission. These biomarkers were in turn significantly associated with lower mean arterial blood pressure, lower cardiac output and lower systemic vascular resistance, and increased need of circulatory support in the initial phase. High levels of TCC and IL-6 at admission were significantly associated with increased 30-days mortality. Conclusion: Inflammatory biomarkers, including complement activation, cytokines and endothelial injury, were associated with increased circulatory failure in the initial period after cardiac arrest.

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• Jørgensen, Silje Fjellgård; Macpherson, Magnhild Eide; Bjørnetrø, Tonje; Holm, Kristian; Kummen, Martin & Rashidi, Azita [Show all 18 contributors for this article] (2024). Retraction to: Rifaximin alters gut microbiota profile, but does not affect systemic inflammation - a randomized controlled trial in common variable immunodeficiency (Scientific Reports, (2019), 9, 1, (167), 10.1038/s41598-018-35367-7). Scientific Reports. ISSN 2045-2322. 14(1). doi: 10.1038/s41598-024-54117-6.
• Hindley, Guy; Drange, Ole Kristian; Lin, Aihua; Kutrolli, Gleda; Shadrin, Alexey & Parker, Nadine [Show all 20 contributors for this article] (2024). Corrigendum to “Cross-trait genome-wide association analysis of C-reactive protein level and psychiatric disorders” [Psychoneuroendocrinology 157 (2023) 106368] (Psychoneuroendocrinology (2023) 157, (S0306453023003463), (10.1016/j.psyneuen.2023.106368)). Psychoneuroendocrinology. ISSN 0306-4530. doi: 10.1016/j.psyneuen.2024.106980.
• Hansen, Ellen-Sofie; Edvardsen, Magnus; Aukrust, Pål; Ueland, Thor; Hansen, John Bjarne & Brækkan, Sigrid Kufaas [Show all 7 contributors for this article] (2024). Galectin-3-binding protein and future venous thromboembolism. Research and Practice in Thrombosis and Haemostasis (RPTH). ISSN 2475-0379. 8(1). doi: 10.1016/j.rpth.2023.102311.
• Risnes, Ivar; Aukrust, Pål; Lundblad, Runar; Ueland, Thor; Rynning, Stein Erik & Solheim, Eivind [Show all 7 contributors for this article] (2023). Troponin T and N-Terminal Pro-Brain Natriuretic Peptide Are Associated with Long-Term All-Cause Mortality in Patients with Post-Sternotomy Mediastinitis following Coronary Artery Bypass Grafting: A 15-Year Follow-Up Study. Cardiology. ISSN 0008-6312. 148(6), p. 599–603. doi: 10.1159/000533631.
• Nilsen, Dennis WT; Aarsetøy, Reidun; Ueland, Thor; Aukrust, Pål; Michelsen, Annika Elisabet & Pønitz, Volker [Show all 9 contributors for this article] (2023). Circulation 2023;148:A14503: Chemokine Ligand 18 (CCL18) is a Long-Term Predictor of All-Cause Mortality, but Did Not Predict CVD Events. Show summary

  Circulation 2023 (Nov.): 148 (Suppl. 1), Abstract 14503. . Chemokines mediate leukocyte recruitment and activation. Chemokine ligand 18 (CCL18) is mainly expressed by a broad range of cells such as monocytes/macrophages and dendritic cells. It is highly expressed in chronic inflammatory diseases, and locally in atherosclerotic plaques, particularly at sites of reduced stability. Circulating CCL18 levels are transiently elevated in patients admitted with unstable angina pectoris, but data on myocardial infarction (MI) are scarce. Aim: To assess the utility of CCL18 as a prognostic marker of CVD in patients hospitalized for chest pain of suspected coronary origin. Methods: The population consisted of 871 consecutive patients (ClinicalTrials.gov Identifier: NCT00521976). Stepwise Cox regression models, applying continuous loge-transformed values, were fitted for each of the biomarkers with all-cause mortality and cardiac death within 24-months and all-cause mortality within median 7 years (y) as the dependent variables, adding an analysis of 1) all-cause mortality or MI, and 2) all-cause mortality or MI or stroke at 7 y follow up (FU). The hazard ratio (HR) (95% CI) was assessed in a univariate and multivariable model, adjusting for traditional clinical cardiovascular risk factors, adding BNP, hsCRP, and TnT. Results: Plasma samples from 849 patients were available. By 24 months FU, 138 (15.8%) patients had died; 86 were cardiac deaths. The univariate analysis showed a positive, significant association between CCL18 and total death [HR 1.55 (95% 1.30-1.83), p=0.000], and for cardiac death [HR 1.32 (95% 1.06-1.64), p=0.013]. Applying multivariable analysis, the associations were no longer significant. At 7 y FU, a total of 332 (38.1%) patients had died. After multivariable adjustment, CLL18 was independently associated with all-cause mortality [HR 1.14 (95% CI, 1.01-1.29), p=0.030], but not for MI (n=203) or stroke (n=55). The positive association between CCL18 and all-cause mortality was lost when combined with CVD events; all-cause mortality or MI (n=404, p=0.75), and all-cause mortality or MI or stroke (n=422, p=0.79). Conclusions: CCL18 predicts long-term all-cause mortality, but had no independent prognostic bearing on short-term cardiac death and CVD events during long-term FU.

• Nilsen, Dennis WT; Pønitz, Volker; Aarsetøy, Reidun; Ueland, Thor; Aukrust, Pål & Michelsen, Annika Elisabet [Show all 9 contributors for this article] (2023). Circulation 2023; 148: Suppl_17 (Nov.). Abstract 14288. α1-Antichymotrypsin Complex (SERPINA3) is an Independent Predictor of Long-Term All-Cause Mortality, but Did Not Predict CVD Events. Show summary

  Circulation 2023:148, Suppl_17: SERPINA3 is an acute phase protein triggered by inflammation. It inhibits neutrophil cathepsin which cleaves protease-activated receptor 4 (PAR-4) via a thrombin-independent pathway, and mast cell chymase which mediates the production of angiotensin-II via an ACE-independent pathway. SERPINA3 is upregulated after an acute myocardial infarction (MI), but data on its long-term prognostic value in MI patients are scarce.Aim: To assess the utility of SERPINA3 as a prognostic marker in patients hospitalized for chest pain of suspected coronary origin.Methods: A total of 871 consecutive patients were included (ClinicalTrials.gov Identifier: NCT00521976). Stepwise Cox regression models, applying continuous loge-transformed values, were fitted for each of the biomarkers with all-cause mortality and cardiac death within median 24-months (mo) and all-cause mortality within median 7 years (y) as the dependent variables, adding an analysis of 1) all-cause mortality or MI, and 2) all-cause mortality or MI or stroke at 7 y follow up (FU). The hazard ratio (HR) (95% CI) was assessed in a univariate and multivariable model, adjusting for traditional clinical cardiovascular risk factors, adding BNP, hsCRP, TnT.Results: Plasma samples from 847 patients were available. At 24 mo FU, 138 (15.8%) patients had died, of which 86 were cardiac deaths. The univariate analysis showed a positive, significant association between SERPINA3 and total death [HR 1.42 (95% 1.19-1.68), p =0.000], but was not significant for cardiac death. Associations after multivariable adjustment were statistically non-significant. At 7 y FU, 332 (38.1%) patients had died. After adjustment, SERPINA3 was independently associated with all-cause mortality [HR 1.14 (95% CI, 1.02-1.28), p=0.022], but not for MI (n=203), and stroke (n=55), respectively, and remained essentially unaffected for all-cause mortality or MI combined (n=404) [HR 1.12 (95% CI, 1.01-1.24), p=0.031], slightly weakened when stroke also was added (n=422) [HR 1.10 (95% CI, 1.00-1.22), p=0.060].Conclusions: SERPINA3 predicts long-term all-cause mortality, but had no prognostic bearing on short-term cardiac death. Introducing non-fatal CVD events during long-term FU did not improve its prognostic value.

• Ueland, Thor; Äikäs, Lauri A.O.; Dahl, Tuva Børresdatter; Gregersen, Ida; Olsen, Maria Belland & Michelsen, Annika Elisabet [Show all 20 contributors for this article] (2023). Low-density lipoprotein particles carrying proinflammatory proteins with altered aggregation pattern detected in COVID-19 patients 3 months after hospitalization. Journal of Infection. ISSN 0163-4453. 86(5), p. 489–492. doi: 10.1016/j.jinf.2023.02.024.
• Nilsen, Dennis W.T.; Røysland, Michelle; Ueland, Thor; Aukrust, Pål; Michelsen, Annika Elisabet & Staines, Harry [Show all 10 contributors for this article] (2022). Circulation 2022;146:A10315.The Effect of Protease-Activated Receptor-1 Inhibition With Vorapaxar in Post-mi and Nstemi Patients on Selected Biomarkers Reflecting Endothelial Function . Show summary

  Circulation 2022;146:A10315 Introduction: Biomarker research related to protease-activated receptor-1 (PAR-1) inhibition with vorapaxar in humans has essentially focused on platelets. Follow-up (FU) time has been short, whereas in the current study, focus has been on endothelial function during both short- and long-term PAR-1 inhibition. Aim: To assess short- and long-term effects of vorapaxar (V) as compared to Placebo (PL) on the following biomarkers: Angiopoietin-2 (ANGPT2), Angiopoietin-like 4 (ANGPTL4), VEGF, ICAM-1, VCAM-1, E-Selectin (ESEL), von Willebrand Factor (VWF), Thrombomodulin (TM), PAI-1 and PAI-2. Methods: In an independent collective subproject performed in Norway, post-MI patients at steady state were recruited from the “Trial to Assess the Effects of Vorapaxar in Preventing Heart Attack and Stroke in Patients with Atherosclerosis” (TRA2ᵒP-TIMI 50) and NSTEMI patients were recruited from the “Thrombin Receptor Antagonist for Clinical Event Reduction in acute coronary syndrome” (TRACER) trial. Biomarkers were measured in duplicate by enzyme immunoassays (EIA) in citrated plasma at one month follow-up and at study completion (median 2.3 years) for subjects recruited from both trials. Results: Biomarkers were measured in 265 consecutive patients [age median 62.0 years (Q1-Q3: 55.0-68.0 years), males 83%] with at least one change from baseline value. Among these, biomarkers were available at both short- and long-term follow-up in 221 subjects. ANGPT2 increased significantly in V as compared to PL at 1-month follow-up in the total population (p=0.034), and in males in both post-MI (p=0.031) and NSTEMI subjects (p=0.012), respectively. ANGPTL4 increased (p=0.028) and PAI-2 decreased (p=0.025) significantly in the total population in favor of V at final FU. In the total post-MI subgroup and among males of that group, a short-term significant increase in ESEL in favor of V was observed, p=0.029 and p=0.018, respectively. Also, a transient significant increase in VWF (p=0.032) in favor of V was seen at one month in NSTEMI patients. Conclusions: Significant changes suggesting potential harmful effects in some biomarkers were observed during 1-month and long-term PAR-1 inhibition as compared to placebo in post-MI and acute coronary syndrome patients.

• Gregersen, Ida; Ueland, Thor; Holter, Jan Cato; Olsen, Maria Belland; Michelsen, Annika Elisabet & Murphy, Sarah L [Show all 22 contributors for this article] (2022). CXCL16 associates with adverse outcome and cardiac involvement in hospitalized patients with Covid-19. Journal of Infection. ISSN 0163-4453. 85(6), p. 735–738. doi: 10.1016/j.jinf.2022.09.029.
• Berg, Janna; Halvorsen, Ann Rita; Bengtson, May-Bente; Lindberg, Morten; Halvorsen, Bente & Aukrust, Pål [Show all 8 contributors for this article] (2022). Corrigendum: Circulating T cell activation and exhaustion markers are associated with radiation pneumonitis and poor survival in non-small-cell lung cancer, (Front. Immunol, (2022), 13, (875152), 10.3389/fimmu.2022.875152). Frontiers in Immunology. ISSN 1664-3224. 13. doi: 10.3389/fimmu.2022.1051156.

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