A prospective study of the sensitivity, specificity and diagnostic performance of soluble intercellular adhesion molecule 1, highly sensitive C-reactive protein, soluble E-selectin and serum amyloid A in the diagnosis of neonatal infection.

BACKGROUND: Diagnosis of neonatal infection is difficult, because of it's non-specific clinical presentation and the lack of reliable diagnostic tests. The purpose of this study was to examine the potential diagnostic value of serum soluble intercellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin), highly sensitive C-reactive protein (hsCRP) and serum amyloid A (SAA) measurements, both individually and in combination in the setting of a neonatal intensive care unit. METHODS: 219 consecutive serum samples were taken from 149 infants undergoing sepsis work up in a neonatal intensive care unit. Clinical diagnosis was established in a prospective manner, blind to the results of the study measurements. Infants were classified by an experienced paediatrician as infected or not-infected, one week after presentation. Classification was based on clinical presentation, routine laboratory and radiological investigations and response to therapy. The infected group were sub-classified as (a) culture positive infection or (b) culture negative infection. sICAM-1, sE-selectin, hsCRP and SAA levels were determined from stored serum samples after diagnosis was established. Further sub-group analysis of results was undertaken according to early or late onset of infection and preterm or term status. Statistical analysis utilised Mann Whitney U test and ROC curve analysis. RESULTS: There were significantly increased serum levels of sICAM-1, hsCRP, E selectin (p < 0.001) and SAA (p = 0.004) in infected infants compared with non-infected. ROC curve analysis indicated area under the curve values of 0.79 (sICAM-1), 0.73 (hsCRP), 0.72 (sE-selectin) and 0.61 (SAA). ROC curve analysis also defined optimum diagnostic cut-off levels for each measurement. The performance characteristics of sICAM-1, hsCRP and sE-selectin included a high negative predictive value (NPV) for culture positive infection and this was enhanced by combination of all 4 measurements. Clinical subgroup analysis suggested particularly high NPV for early onset symptoms, however further studies are required to elucidate this finding. CONCLUSIONS: All four study measurements demonstrated some diagnostic value for neonatal infection however sICAM-1, hsCRP and sE-selectin demonstrated the highest NPV individually. The optimum diagnostic cut off level for hsCRP measurement in this study was much lower than currently used in routine clinical practice. Use of a combination of measurements enhanced diagnostic performance, demonstrating sensitivity of 90.3% and NPV of 91.3%. This study suggests there may be value in use of several of these markers, individually and in combination to assist in excluding neonatal infection. Further work is needed to confirm a specific role in the exclusion of early onset infection.

The clinical effect of dietary supplementation with omega-3 fish oils and/or copper in systemic lupus erythematosus.

OBJECTIVE: To determine the effect of dietary supplementation with omega-3 fish oils with or without copper on disease activity in systemic lupus erythematosus (SLE). Fish oil supplementation has a beneficial effect on murine models of SLE, while exogenous copper can decrease the formation of lupus erythematosus cells in rats with a hydralazine-induced collagen disease. METHODS: A double blind, double placebo controlled factorial trial was performed on 52 patients with SLE. Patients were randomly assigned to 4 treatment groups. Physiological doses of omega-3 fish oils and copper readily obtainable by dietary means were used. One group received 3 g MaxEPA and 3 mg copper, another 3 g MaxEPA and placebo copper, another 3 mg copper and placebo fish oil, and the fourth group received both placebo capsules. Serial measurements of disease activity using the revised Systemic Lupus Activity Measure (SLAM-R) and peripheral blood samples for routine hematological, biochemical, and immunological indices were taken at baseline, 6, 12, and 24 weeks. RESULTS: There was a significant decline in SLAM-R score from 6.12 to 4.69 (p < 0.05) in those subjects taking fish oil compared to placebo. No significant effect on SLAM-R was observed in subjects taking copper. Laboratory variables were unaffected by either intervention. CONCLUSION: In the management of SLE, dietary supplementation with fish oil may be beneficial in modifying symptomatic disease activity.

A comparison of antibodies to tissue transglutaminase with conventional serological tests in the diagnosis of coeliac disease.

BACKGROUND: Tissue transglutaminase is now recognized as the autoantigen for antiendomysial antibodies. Antibodies to tissue transglutaminase have been proposed as a valuable test for coeliac disease. OBJECTIVE: To determine the value of antibodies to tissue transglutaminase in the diagnosis of coeliac disease in our outpatient population. METHODS: Patients who underwent serological tests for coeliac disease during the first 18 months of the tissue transglutaminase antibody assay were retrospectively identified from the regional serology laboratory database. Patients' symptoms were noted, along with serological results and duodenal histology in those patients who underwent duodenal biopsy. RESULTS In total, 586 patients were identified as having been serologically tested for coeliac disease, of whom 92 patients (33 men; mean age 51.7 years) had been followed up with duodenal biopsies. Of these 92 patients, 29 (31%; 14 men; mean age 52.5 years) had histological features of coeliac disease. The 63 patients with normal histology (19 men; mean age 51.8 years) acted as controls. Weight loss was more frequent in coeliac disease patients compared to controls (7 vs 5; P = 0.04) whereas the frequency of anaemia (P = 0.85) and diarrhoea (P = 0.74) did not differ significantly between the two groups. The sensitivity and specificity of tissue transglutaminase antibodies (86%; 84%) were compared to those for antiendomysial antibodies (90%; 98%) and antigliadin antibodies (76%; 79%). CONCLUSIONS: The diagnostic value of tissue transglutaminase antibodies was intermediate between that of antiendomysial antibodies and antigliadin antibodies. However, duodenal biopsy remains the gold standard diagnostic test for coeliac disease.