Kristian Kofoed

A 28 year-old man with ulcerative colitis treated for 10 years with azathioprine (AZA) returned from Central Asia with fever, swollen lymph glands, hepatosplenomegaly, and pancytopenia. He was tested positive for acute Epstein-Barr virus (EBV) infection. Before the final diagnosis of EBV-associated large B-cell lymphoma was confirmed, he died from multiple organ failure. AZA and 6-mercaptopurine are associated with the development of EBV-positive lymphomas in organ-transplanted patients. This type of lymphoma is a rare complication in inflammatory bowel disease.

Better outcomes in patients suspected of community-acquired infections requires the optimal and timely assessment of disease severity at the point of first contact with the health care system, which is typically in the emergency department. This study was conducted using a previously described, prospectively collected cohort of patients with systemic inflammatory response syndrome (SIRS) that were admitted to an emergency department and a department of infectious diseases at a university hospital. Plasma samples were collected and disease severity scores calculated upon admission. A multiplex immunoassay and a newly developed enzyme-linked immunosorbent assay (ELISA)-based assay were used to measure the soluble urokinase-type plasminogen activator receptor, soluble triggering receptor expressed on myeloid cells-1, and macrophage migration inhibitory factor. The area under the receiver operating characteristic (ROC) curve for the prediction of 30- and 180-day mortality was used to compare the performance of the markers and the models. A total of 151 patients were eligible for analysis. Of these, nine died before day 30 and 19 died before day 180 post-admission. Admission-soluble urokinase-type plasminogen activator receptor levels were significantly higher in both day 30 and day 180 non-survivors. There was a non-significant trend towards higher macrophage migration inhibitory factor concentrations in day 30 non-survivors. Soluble triggering receptor expressed on myeloid cells-1 levels were significantly lower in non-survivors at both time points. The simplified acute physiology score II (SAPS II) and sequential organ failure assessment (SOFA) scores were significantly higher in non-survivors at both time points, indicating that these models intended for use in intensive care units might also be useful in an emergency department setting.

Introduction: Accurate and timely diagnosis of community-acquired bacterial infections in patients with systemic inflammation remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival. We therefore compared the diagnostic characteristics of novel and routinely used biomarkers of sepsis alone and in combination. Methods: This prospective cohort study included patients with systemic inflammatory response syndrome who were suspected of having community-acquired infections. It was conducted in a medical emergency department and department of infectious diseases at a university hospital. A multiplex immunoassay measuring soluble urokinase-type plasminogen activator (suPAR) and soluble triggering receptor expressed on myeloid cells (sTREM)-1 and macrophage migration inhibitory factor (MIF) was used in parallel with standard measurements of C-reactive protein (CRP), procalcitonin (PCT), and neutrophils. Two composite markers were constructed – one including a linear combination of the three best performing markers and another including all six – and the area under the receiver operating characteristic curve (AUC) was used to compare their performance and those of the individual markers. Results: A total of 151 patients were eligible for analysis. Of these, 96 had bacterial infections. The AUCs for detection of a bacterial cause of inflammation were 0.50 (95% confidence interval [CI] 0.40 to 0.60) for suPAR, 0.61 (95% CI 0.52 to 0.71) for sTREM-1, 0.63 (95% CI 0.53 to 0.72) for MIF, 0.72 (95% CI 0.63 to 0.79) for PCT, 0.74 (95% CI 0.66 to 0.81) for neutrophil count, 0.81 (95% CI 0.73 to 0.86) for CRP, 0.84 (95% CI 0.71 to 0.91) for the composite three-marker test, and 0.88 (95% CI 0.81 to 0.92) for the composite six-marker test. The AUC of the six-marker test was significantly greater than that of the single markers. Conclusion: Combining information from several markers improves diagnostic accuracy in detecting bacterial versus nonbacterial causes of inflammation. Measurements of suPAR, sTREM-1 and MIF had limited value as single markers, whereas PCT and CRP exhibited acceptable diagnostic characteristics. Trial registration: NCT 00389337