.  Eugen‐Olsen J, Andersen O, Linneberg A, Ladelund S, Hansen TW, Langkilde A, Petersen J, Pielak T, Møller LN, Jeppesen J, Lyngbæk S, Fenger M, Olsen MH, Hildebrandt PR, Borch‐Johnsen K, Jørgensen T, Haugaard SB (Copenhagen University, Hvidovre Hospital, Hvidovre; Copenhagen University Hospital, Glostrup; Copenhagen University Hospital, Copenhagen; Copenhagen University Hospital, Glostrup; Copenhagen University, Hvidovre Hospital, Hvidovre; Steno Diabetes Center, Gentofte; University of Aarhus, Aarhus; University of Copenhagen, Copenhagen; Copenhagen University, Hvidovre Hospital, Hvidovre, Denmark). Circulating soluble urokinase plasminogen activator receptor predicts cancer, cardiovascular disease, diabetes and mortality in the general population. J Intern Med 2010; 268: 296–308. Background.  Low‐grade inflammation is thought to contribute to the development of cardiovascular disease (CVD), type‐2 diabetes mellitus (T2D), cancer and mortality. Biomarkers of inflammation may aid in risk prediction and enable early intervention and prevention of disease. Objective.  The aim of this study was to investigate whether plasma levels of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) are predictive of disease and mortality in the general population. Design.  This was an observational prospective cohort study. Cohort participants were included from June 1993 to December 1994 and followed until the end of 2006. Setting.  General adult Caucasian population. Participants.  The MONICA10 study, a population‐based cohort recruited from Copenhagen, Denmark, included 2602 individuals aged 41, 51, 61 or 71 years. Measurements.  Blood samples were analysed for suPAR levels using a commercially available enzyme‐linked immunosorbent assay. Risk of cancer (n = 308), CVD (n = 301), T2D (n = 59) and mortality (n = 411) was assessed with a multivariate proportional hazards model using Cox regression. Results.  Elevated baseline suPAR level was associated with an increased risk of cancer, CVD, T2D and mortality during follow‐up. suPAR was more strongly associated with cancer, CVD and mortality in men than in women, and in younger compared with older individuals. suPAR remained significantly associated with the risk of negative outcome after adjustment for a number of relevant risk factors including C‐reactive protein levels. Limitation.  Further validation in ethnic populations other than Caucasians is needed. Conclusion.  The stable plasma protein suPAR may be a promising biomarker because of its independent association with incident cancer, CVD, T2D and mortality in the general population.

Background: Soluble urokinase plasminogen activator receptor (suPAR) is a stable plasma biomarker associated with inflammation and disease. This study tested the association between suPAR levels and incident respiratory, gastrointestinal, or other types of cancer in initially cancer-free individuals from a general population-based prospective study.Methods: Baseline plasma samples, baseline characteristics, and follow-up data were available from 2,656 individuals from the population-based Danish MONICA10 (MONItoring trends and determinants of CArdiovascular disease) study, followed for a median of 12.6 years. Cancer was diagnosed according to international classification of diseases (ICD) 8 and ICD-10 codes and suPAR levels were measured using a commercially available ELISA. The association of suPAR levels with incident cancer during follow-up was analyzed using Cox regression, adjusted for established risk factors and the inflammatory markers C-reactive protein (CRP) and leukocyte numbers.Results: suPAR levels ranged from 0.6 to 22 ng/mL and median suPAR level was 4.01 ng/mL. An increase of 1 ng/mL in baseline suPAR was associated with adjusted HR of 1.61 (95% CI: 1.23-2.11, P < 0.001), 0.92 (95% CI: 0.69-1.24, P ¼ 0.59), and 1.33 (95% CI: 1.13-1.58, P < 0.001) of being diagnosed with respiratory, gastrointestinal, and other cancer types, respectively.Conclusion: Elevated suPAR levels were associated with increased risk of incident respiratory cancer and other types of cancer, but not gastrointestinal cancers, independently of established risk factors, CRP, and leukocyte numbers.Impact: These findings suggest that inflammation is involved in cancer development. Risk algorithms based on established risk factors and risk-associated biomarkers should be developed and evaluated in large, general population-based studies. We suggest suPAR as a candidate for evaluation in cancer risk algorithms. Cancer Epidemiol Biomarkers Prev; 20(4); 609-18. Ó2011 AACR.

BackgroundTNF-α plays a role in angiogenesis and collagen synthesis, both essential in the wound healing process. There are concerns that pre-operative anti-TNF-α treatment may influence the surgical stress response and increase the risk of surgical complications. The aim of this study was to describe the surgical stress response in patients with inflammatory bowel disease (IBD) and to investigate whether the pre-operative administration of anti-tumor necrosis factor alpha (anti-TNF-α) agents modify the surgical stress response.MethodsThis was a prospective, multi-center cohort pilot study. The primary outcome was the change in concentration of immunological biomarkers of the surgical stress response (TNF-α, IL-6, and IL-10). Secondary outcome measures were changes in IL-8, IL-17A, C-reactive protein, white blood cells, cortisol, transferrin, ferritin, and D-Dimer in addition to 30 days’ post-operative complications and length of post-operative stay in the hospital (LOS).ResultsForty-six patients with IBD undergoing major abdominal surgery were included, and 18 received anti-TNF- α treatment pre-operatively. Peak increase of most of the immunological biomarkers occurred 6 hours after surgical incision. Then the concentration decreased after 24 h followed by a plateau at 48 h. After adjusting for confounders including detectable blood concentrations, no difference in the concentrations of immunological, endocrinological or haematological biomarkers of stress was found between anti-TNF-α treated and anti-TNF-α naïve patients. No increase in post-operative complications or LOS was noticed in patients who received anti-TNF-α treatment.ConclusionsAnti-TNF-α did not affect surgical stress response in this pilot study. Withdrawal of anti-TNF-α drugs prior to surgical intervention in IBD patients might not be justified without measurement of drug concentration and drug antibodies.Trial registrationClinicaltrails.gov.: NCT01974869.

NCT01351831.