.  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.

Meta-analysis suggests that mutations in KRAS exons 3 and 4, NRAS, BRAF and PIK3CA and non-functional PTEN predict resistance to anti-EGFR therapies and demonstrates that biomarker analysis beyond KRAS exon 2 should be implemented for prediction of clinical benefit from anti-EGFR antibodies in metastatic colorectal cancer.

SUMMARYAgeing is associated with low-grade inflammation and markers such as IL-6 possess prognostic value. Tumour necrosis-alpha (TNF-a ) initiates the inflammatory cascade and has been linked to several ageassociated disorders. It remains, however, unknown if TNF-a is associated with mortality in old populations. The aim of the present study was to investigate if serum levels of TNF-a were associated with all-cause mortality independently of interleukin (IL)-6 in a prospective study of 333 relatively healthy 80-year-old people. A Cox regression model was used to explore effects of TNF-a and IL-6 on survival in the following 6 years. A total of 133 participants died during this follow-up period. TNF-a was associated with mortality in men, but not in women, whereas low-grade elevations in IL-6 were associated strongly with mortality in both sexes. TNF-a explained only 7% of the variability in IL-6 and effects of the two cytokines were independent of each other as well as of other traditional risk factors for death [smoking, blood pressure, physical exercise, total cholesterol, co-morbidity, body mass index (BMI) and intake of anti-inflammatory drugs]. These findings indicate that at least in old populations chronic elevated levels of TNF-a and IL-6 have different biological functions that trigger age-associated pathology and cause mortality.

Editor's key points † There is considerable interest in the effects of steroids in the perioperative period. † There is already evidence of beneficial effects on pain and nausea, although not in this patient population. † Using predefined criteria, this study comprehensively assessed the postoperative effects of i.v. methylprednisolone (MP) on function and pain. † There was no improvement in functional discharge criteria using MP, although pain control was better.Background. High-dose glucocorticoid may reduce postsurgical pain and improve recovery. We hypothesized that 125 mg methylprednisolone (MP) would reduce time to meet functional discharge criteria after total hip arthroplasty (THA).Methods. Forty-eight patients undergoing unilateral THA under spinal anaesthesia were consecutively included in this randomized, double-blind, placebo-controlled trial receiving preoperative i.v. MP or saline. All patients received a standardized, multimodal analgesic regime with paracetamol, celecoxib, and gabapentin. The primary outcome was time to meet well-defined functional discharge criteria. Secondary outcomes were handgrip strength and endurance, pain, nausea, vomiting, fatigue, sleep quality, and rescue analgesic-, antiemetic-, and hypnotic medicine requirements. The inflammatory response measured by C-reactive protein (CRP) and actual length of stay were also registered. Discharge criteria were assessed twice daily (at 09:00 and 14:00 h) until discharge. Other outcomes were assessed at 2, 4, 6, 8, and 24 h after operation, and also in a questionnaire from postoperative day (POD) 1-4. Results. Time to meet discharge criteria was [median (IQR) (95% CI), MP vs placebo]: 23.5 (23.3 -23.7) (17.8 -43.8) vs 23.5 (23.0 -23.8) (20.0 -46.8) h, the mean difference (95% CI) being 21.3 (24.7 to 2.2) h, P¼0.65. Overall pain for the first 24 h after surgery was significantly reduced in the MP vs the placebo group (P,0.01), as was CRP at 24 h (P,0.0001). No other between-group differences were observed. No drug-related complications were observed at follow-up on POD30.Conclusions. MP 125 mg i.v. before surgery added to a multimodal oral analgesic regime did not reduce time to meet functional discharge criteria after THA, but improved analgesia for the first 24 h.

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