• Cytokine pattern in patients with ST-elevation myocardial infarction treated with the interleukin-6 receptor antagonist tocilizumab 

      Woxholt, Sindre; Ueland, Thor; Aukrust, Pål; Anstensrud, Anne Kristine; Broch, Kaspar; Tøllefsen, Ingvild Maria; Ryan, Liv; Bendz, Bjørn; Hopp, Einar; Kløw, Nils-Einar; Seljeflot, Ingebjørg; Halvorsen, Bente; Dahl, Tuva Børresdatter; Huse, Camilla; Andersen, Geir Øystein; Gullestad, Lars; Wiseth, Rune; Amundsen, Brage H.; Damås, Jan Kristian; Kleveland, Ola (Journal article; Tidsskriftartikkel; Peer reviewed, 2023-08-17)
      Background - Tocilizumab improves myocardial salvage index (MSI) in patients with ST-elevation myocardial infarction (STEMI), but its mechanisms of action are unclear. Here, we explored how cytokines were affected by tocilizumab and their correlations with neutrophils, C-reactive protein (CRP), troponin T, MSI and infarct size.<p> <p>Methods - STEMI patients were randomised to receive a single ...
    • Detailed stratified GWAS analysis for severe COVID-19 in four European populations 

      Ellinghaus, David; Degenhardt, Frauke; Juzenas, Simonas; Lerga-Jaso, Jon; Wendorff, Mareike; Maya-Miles, Douglas; Uellendahl-Werth, Florian; ElAbd, Hesham; Lenning, Ole Bernt; Myhre, Ronny; Vadla, May Sissel; Holten, Aleksander Rygh; Kildal, Anders Benjamin; Lind, Andreas; Dyrhol-Riise, Anne Ma; Hoff, Dag Arne Lihaug; Müller, Fredrik; Solligård, Erik; Holter, Jan Cato; Afset, Jan Egil; Damås, Jan Kristian; Bergan, Jonas; Risnes, Kari; Muller, Karl Erik; Tonby, Kristian; Heggelund, Lars; Tuset Gustad, Trine; Grimsrud, Marit Mæhle; Dudman, Susanne Gjeruldsen; Folseraas, Trine; Skogen, Vegard; Hov, Johannes Espolin Roksund; Karlsen, Tom Hemming (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-07-15)
      Given the highly variable clinical phenotype of Coronavirus disease 2019 (COVID-19), a deeper analysis of the host genetic contribution to severe COVID-19 is important to improve our understanding of underlying disease mechanisms. Here, we describe an extended GWAS meta-analysis of a well-characterized cohort of 3255 COVID-19 patients with respiratory failure and 12 488 population controls from ...
    • Explaining sex differences in risk of bloodstream infections using mediation analysis in the population-based HUNT study in Norway 

      Mohus, Randi Marie; Gustad, Lise Tuset; Furberg, Anne-Sofie; Moen, Martine Kjølberg; Liyanarachi, Kristin Vardheim; Askim, Åsa Susanne; Åsberg, Signe Elisabeth; DeWan, Andrew T.; Rogne, Tormod; Simonsen, Gunnar Skov; Nilsen, Tom Ivar Lund; Åsvold, Bjørn Olav; Damås, Jan Kristian; Solligård, Erik (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-05-19)
      Previous studies indicate sex differences in incidence and severity of bloodstream infections (BSI). We examined the effect of sex on risk of BSI, BSI mortality, and BSI caused by the most common infecting bacteria. Using causal mediation analyses, we assessed if this effect is mediated by health behaviours (smoking, alcohol consumption), education, cardiovascular risk factors (systolic blood pressure, ...
    • IL-6 receptor inhibition by tocilizumab attenuated expression of C5a receptor 1 and 2 in non-ST-elevation myocardial infarction 

      Orrem, Hilde Lang; Nilsson, Per; Pischke, Søren Erik; Kleveland, Ola; Yndestad, Arne; Ekholt, Karin; Damås, Jan Kristian; Espevik, Terje; Bendz, Bjørn; Halvorsen, Bente; Gregersen, Ida; Wiseth, Rune; Andersen, Geir Øystein; Ueland, Thor; Gullestad, Lars; Aukrust, Pål; Barratt-Due, Andreas; Mollnes, Tom Eirik (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-09-12)
      <p><i>Background</i>: Elevated interleukin-6 (IL-6) and complement activation are associated with detrimental effects of inflammation in coronary artery disease (CAD). The complement anaphylatoxins C5a and C3a interact with their receptors; the highly inflammatory C5aR1, and the C5aR2 and C3aR. We evaluated the effect of the IL-6 receptor (IL-6R)-antagonist tocilizumab on the expression of the ...
    • Inflammatory Markers and Radiotherapy Response in Patients With Painful Bone Metastases 

      Habberstad, Ragnhild H; Aass, Nina Kathrine; Mollnes, Tom Eirik; Damås, Jan Kristian; Brunelli, Cinzia; Rossi, Romina; Garcia-Alonso, Elena; Kaasa, Stein; Klepstad, Pål (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-07-05)
      <p><b> Context</b> Inflammation is proposed to influence tumor response in radiotherapy (RT). Clinical studies to investigate the relationship between inflammatory markers and RT response is warranted to understand the variable RT efficacy in patients with painful bone metastases. <p><b> Objectives</b> To evaluate the association between inflammatory markers and analgesic response to RT in ...
    • The inflammatory response is related to circulatory failure after out-of-hospital cardiac arrest: A prospective cohort study 

      Langeland, Halvor Johannes Breivik; Damås, Jan Kristian; Mollnes, Tom Eirik; Ludviksen, Judith K; Ueland, Thor; Michelsen, Annika Elisabet; Løberg, Magnus; Bergum, Daniel; Nordseth, Trond; Skjærvold, Nils Kristian; Klepstad, Pål (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-11-24)
      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 ...
    • Interleukin-6 inhibition in ST-elevation myocardial infarction: Immune cell profile in the randomised ASSAIL-MI trial 

      Huse, Camilla; Anstensrud, Anne Kristine; Michelsen, Annika Elisabet; Ueland, Thor; Broch, Kaspar; Woxholt, Sindre; Yang, Kuan; Sharma, Kapil Kishore; Tøllefsen, Ingvild Maria; Bendz, Bjørn; Amundsen, Brage H.; Damås, Jan Kristian; Berg, Erlend Sturle; Bjørkelund, Elisabeth; Quiles-Jiménez, Ana M T; Bjerkeli, Vigdis; Bendz, Christina; Kleveland, Ola; Stensæth, Knut Haakon; Opdahl, Anders; Kløw, Nils-Einar; Andersen, Geir Øystein; Wiseth, Rune; Halvorsen, Bente; Gullestad, Lars; Seljeflot, Ingebjørg; Aukrust, Pål; Osnes, Liv T. N.; Dahl, Tuva Børresdatter (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-04-30)
      Background We recently showed that interleukin (IL)-6 inhibition by tocilizumab improves myocardial salvage in ST-elevation myocardial infarction (STEMI). However, the mechanisms for this effect are not clear.<p> <p>Methods In this exploratory sub-study of the ASSAIL-MI trial, we examined leukocyte differential counts and their relation to myocardial salvage and peak troponin T (TnT) in STEMI ...
    • Interleukin-6 receptor inhibition with tocilizumab induces a selective and substantial increase in plasma IP-10 and MIP-1β in non-ST-elevation myocardial infarction 

      Kleveland, Ola; Ueland, Thor; Kunszt, Gabor; Bratlie, Marte; Yndestad, Arne; Broch, Kaspar; Holte, Espen; Ryan, Liv; Amundsen, Brage H.; Bendz, Bjørn; Aakhus, Svend; Espevik, Terje; Halvorsen, Bente; Mollnes, Tom Eirik; Wiseth, Rune; Gullestad, Lars; Aukrust, Pål; Damås, Jan Kristian (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-06-29)
      <p><i>Aim</i>: To evaluate the effect of interleukin-6 inhibition with tocilizumab on the cytokine network in patients with acute non-ST-elevation myocardial infarction (NSTEMI).</p> <p><i>Methods</i>: 117 patients with acute NSTEMI were randomised to an intravenous infusion of 280 mg tocilizumab or placebo prior to coronary angiography. Blood samples were obtained at baseline, at 6 consecutive ...
    • IP-10 differentiates between active and latent tuberculosis irrespective of HIV status and declines during therapy 

      Wergeland, Ida; Pullar, Nadine Durema; Assmus, Jörg; Ueland, Thor; Tonby, Kristian; Feruglio, Siri; Kvale, Dag; Damås, Jan Kristian; Aukrust, Pål; Mollnes, Tom Eirik; Dyrhol-Riise, Anne Ma (Journal article; Tidsskriftartikkel; Peer reviewed, 2015-01-15)
      Objectives: Biomarkers for diagnosis and therapy efficacy in tuberculosis (TB) are requested. We have studied biomarkers that may differentiate between active and latent TB infection (LTBI), the influence of HIV infection and changes during anti-TB chemotherapy. Methods: Thirty-eight plasma cytokines, assessed by multiplex and enzyme immunoassays, were analyzed in patients with active TB before ...
    • Mapping the human genetic architecture of COVID-19 

      Niemi, Mari E.K.; Karjalainen, Juha; Liao, Rachel G.; Neale, Benjamin M.; Daly, Mark; Ganna, Andrea; Pathak, Gita A.; Andrews, Shea J.; Kanai, Masahiro; Veerapen, Kumar; Fernandez-Cadenas, Israel; Schulte, Eva C.; Striano, Pasquale; Afset, Jan Egil; Solligård, Erik; Damås, Jan Kristian; Risnes, Kari; Bettini, Laura Rachele; Gustad, Lise Tuset; Holter, Jan Cato; Hov, Johannes Espolin Roksund; Karlsen, Tom Hemming; Folseraas, Trine; Holten, Aleksander Rygh; Dyrhol-Riise, Anne Ma; Tonby, Kristian; Lind, Andreas; Müller, Fredrik; Dudman, Susanne Gjeruldsen; Grimsrud, Marit Mæhle; Vadla, May Sissel; Myhre, Ronny; Kildal, Anders Benjamin; Hoff, Dag Arne Lihaug; Muller, Karl Erik; Heggelund, Lars; Bergan, Jonas; Skogen, Vegard (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-07-08)
      The genetic make-up of an individual contributes to the susceptibility and response to viral infection. Although environmental, clinical and social factors have a role in the chance of exposure to SARS-CoV-2 and the severity of COVID-191,2, host genetics may also be important. Identifying host-specific genetic factors may reveal biological mechanisms of therapeutic relevance and clarify causal ...
    • Monocyte/macrophage and T cell activation markers are not independently associated with MI risk in healthy individuals - results from the HUNT Study 

      Ueland, Thor; Laugsand, Lars Erik; Vatten, Lars Johan; Janszky, Imre; Platou, Carl Geoffrey Parrinder; Michelsen, Annika; Damås, Jan Kristian; Aukrust, Pål; Åsvold, Bjørn Olav (Journal article; Tidsskriftartikkel; Peer reviewed, 2017-06-06)
      <p><i>Background</i>: We hypothesized that circulating markers reflecting monocyte/macrophage and T cell activation are associated with increased risk of myocardial infarction (MI) in apparently healthy individuals.</p> <p><i>Methods</i>: Serum monocyte/macrophage and T cell activation markers soluble (s) CD163, sCD14, Gal3BP, sCD25 and sCD166 were analyzed by enzyme-immunoassay in a case-control ...
    • Novel Insights Into the Effects of Interleukin 6 Antagonism in Non-ST-Segment-Elevation Myocardial Infarction Employing the SOMAscan Proteomics Platform 

      George, Marc J; Kleveland, Ola; Garcia-Hernandez, Jorge; Palmen, Jutta; Lovering, Ruth; Wiseth, Rune; Aukrust, Pål; Engmann, Jorgen; Damås, Jan Kristian; Hingorani, Aroon D; Gullestad, Lars; Casas, Juan P; Ueland, Thor (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-06-09)
      <p>Background: Interleukin 6 concentration is associated with myocardial injury, heart failure, and mortality after myocardial infarction. In the Norwegian tocilizumab non-ST-segment-elevation myocardial infarction trial, the first randomized trial of interleukin 6 blockade in myocardial infarction, concentration of both C-reactive protein and troponin T were reduced in the active treatment arm. In ...
    • The Palliative Radiotherapy and Inflammation Study (PRAIS) - Protocol for a longitudinal observational multicenter study on patients with cancer induced bone pain 11 Medical and Health Sciences 1103 Clinical Sciences 

      Habberstad, Ragnhild H; Frøseth, Trude Camilla Salvesen; Aass, Nina Kathrine; Abramova, Tatiana Mikhailovna; Baas, Theo; Mørkeset, Siri Tessem; Caraceni, Augusto; Laird, Barry J; Boland, Jason W.; Rossi, Romina; Garcia-Alonso, Elena; Stensheim, Hanne; Loge, Jon Håvard; Hjermstad, Marianne Jensen; Bjerkeset, Ellen; Bye, Asta; Lund, Jo-Åsmund; Solheim, Tora Skeidsvoll; Vagnildhaug, Ola Magne; Brunelli, Cinzia; Damås, Jan Kristian; Mollnes, Tom Eirik; Kaasa, Stein; Klepstad, Pål (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-09-28)
      <i><p>Background</i>: Radiation therapy (RT) results in pain relief for about 6 of 10 patients with cancer induced bone pain (CIBP) caused by bone metastases. The high number of non-responders, the long median time from RT to pain response and the risk of adverse effects, makes it important to determine predictors of treatment response. Clinical features such as cancer type, performance status and ...
    • Predicting in-hospital death from derived EHR trajectory features 

      Bopche, Rajeev; Gustad, Lise Tuset; Afset, Jan Egil; Damås, Jan Kristian; Nytrø, Øystein (Chapter; Bokkapittel, 2023)
      Medical histories of patients can provide insight into the immediate future of a patient. While most studies propose to predict survival from vital signs and hospital tests within one episode of care, we carry out selective feature engineering from longitudinal historical medical records in this study to develop a dataset with derived features. We then train multiple machine learning models for the ...
    • Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction 

      Broch, Kaspar; Anstensrud, Anne Kristine; Woxholt, Sindre; Sharma, Kapil Kishore; Tøllefsen, Ingvild Maria; Bendz, Bjørn; Aakhus, Svend; Ueland, Thor; Amundsen, Brage H.; Damås, Jan Kristian; Berg, Erlend; Bjørkelund, Elisabeth; Bendz, Christina; Hopp, Einar; Kleveland, Ola; Stensæth, Knut Haakon; Opdahl, Anders; Kløw, Nils-Einar; Seljeflot, Ingebjørg; Andersen, Geir Øystein; Wiseth, Rune; Aukrust, Pål; Gullestad, Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-04-12)
      <p><i>Background - </i>Prompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response. <p><i>Objectives - </i>This study sought ...
    • Rationale for the ASSAIL-MI-trial: a randomised controlled trial designed to assess the effect of tocilizumab on myocardial salvage in patients with acute ST-elevation myocardial infarction (STEMI) 

      Anstensrud, Anne Kristine; Voxholt, Sindre; Sharma, Kapil; Broch, Kaspar; Bendz, Bjørn; Aakhus, Svend; Ueland, Thor; Amundsen, Brage H.; Damås, Jan Kristian; Hopp, Einar; Kleveland, Ola; Stensæth, Knut Haakon; Opdahl, Anders; Kløw, Nils-Einar; Seljeflot, Ingebjørg; Andersen, Geir Øystein; Wiseth, Rune; Aukrust, Pål; Gullestad, Lars (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-10-15)
      <i>Introduction</i>: Interleukin-6 (IL-6) may be involved in ischaemia-reperfusion injury and myocardial remodelling after myocardial infarction (MI). We have recently shown that IL-6 inhibition by tocilizumab attenuates systemic inflammation and troponin T-release in patients with acute non-ST elevation MI (NSTEMI). Experimental studies suggest that IL-6 inhibition can limit infarct size through ...
    • Risk of lower respiratory tract infections: a genome-wide association study with Mendelian randomization analysis in three independent European populations 

      Flatby, Helene Marie; Rasheed, Humaira; Ravi, Anuradha; Thomas, Laurent; Liyanarachi, Kristin Vardheim; Afset, Jan Egil; DeWan, Andrew; Brumpton, Ben Michael; Hveem, Kristian; Åsvold, Bjørn Olav; Simonsen, Gunnar Skov; Furberg, Anne-Sofie; Damås, Jan Kristian; Solligård, Erik; Rogne, Tormod (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-11-09)
      Objective: Lower respiratory tract infections (LRTIs) are a leading cause of morbidity and mortality worldwide. Few studies have previously investigated the genetic susceptibility and potential risk factors for LRTI. Methods: We used data from UK Biobank, HUNT, and FinnGen, to conduct a genome-wide association study (GWAS). Cases were subjects hospitalized with LRTI, and controls were subjects with ...
    • SARS-CoV-2 Nsp13 encodes for an HLA-E-stabilizing peptide that abrogates inhibition of NKG2A-expressing NK cells 

      Hammer, Quirin; Dunst, Josefine; Christ, Wanda; Picarazzi, Francesca; Wendorff, Mareike; Momayyezi, Pouria; Huhn, Oisín; Netskar, Herman Krogstad; Maleki, Kimia T.; García, Marina; Sekine, Takuya; Sohlberg, Ebba; Azzimato, Valerio; Aouadi, Myriam; Holten, Aleksander Rygh; Kildal, Anders Benjamin; Lind, Andreas; Dyrhol-Riise, Anne Ma; Hoff, Dag Arne Lihaug; Solligård, Erik; Holter, Jan Cato; Afset, Jan Egil; Damås, Jan Kristian; Hov, Johannes Espolin Roksund; Bergan, Jonas; Risnes, Kari; Muller, Karl Erik; Tonby, Kristian; Heggelund, Lars; Gustad, Lise Tuset; Grimsrud, Marit Mæhle; Vadla, May Sissel; Lenning, Ole Bernt; Myhre, Ronny; Haider, Sammra; Dudman, Susanne Gjeruldsen; Karlsen, Tom Hemming; Folseraas, Trine; Skogen, Vegard; Degenhardt, Frauke; Franke, Andre; Spallotta, Francesco; Mori, Mattia; Michaëlsson, Jakob; Björkström, Niklas K.; Rückert, Timo; Romagnani, Chiara; Horowitz, Amir; Klingström, Jonas; Ljunggren, Hans-Gustaf; Malmberg, Karl-Johan (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-02-21)
      Natural killer (NK) cells are innate immune cells that contribute to host defense against virus infections. NK cells respond to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro and are activated in patients with acute coronavirus disease 2019 (COVID-19). However, by which mechanisms NK cells detect SARS-CoV-2-infected cells remains largely unknown. Here, we show that the ...
    • Secreted wnt antagonists in scrub typhus 

      Ueland, Thor; Astrup, Elisabeth; Otterdal, Kari; Lekva, Tove; Janardhanan, Jeshina; Prakash, John A.; Thomas, Kurien; Michelsen, Annika; Aukrust, Pål; Varghese, George M.; Damås, Jan Kristian (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-04-29)
      Background - The mechanisms that control local and systemic inflammation in scrub typhus have only been partially elucidated. The wingless (Wnt) signaling pathways are emerging as important regulators of inflammation and infection, but have not been investigated in scrub typhus. <p> <p>Methodology/Principal findings - Plasma levels of secreted Wnt antagonists (i.e. DKK-1, sFRP-3, WIF-1 and SOST) ...
    • Serum PCSK9 is modified by interleukin-6 receptor antagonism in patients with hypercholesterolaemia following non-ST-elevation myocardial infarction 

      Ueland, Thor; Kleveland, Ola; Michelsen, Annika; Wiseth, Rune; Damås, Jan Kristian; Aukrust, Pål; Gullestad, Lars; Halvorsen, Bente; Yndestad, Arne (Journal article; Tidsskriftartikkel; Peer reviewed, 2018-09-18)
      <p><i>Objective</i>: It is unclear if activation of inflammatory pathways regulates proprotein convertase subtilisin-kexin type 9 (PCSK9) levels.</p> <p><i>Approach</i>: We evaluated (1) the temporal course of serum PCSK9 during hospitalisation following acute coronary syndrome and associations with markers of inflammation (leucocyte counts, interleukin (IL)-6, C-reactive protein) and lipid levels ...