Diagnostic yield of FDG-PET/CT in fever of unknown origin: a systematic review, meta-analysis, and Delphi exercise.

AIM: To perform a systematic review, meta-analysis and Delphi exercise to evaluate diagnostic yield of combined 2-[18F]-fluoro-2-deoxy-d-glucose (FDG) positron-emission tomography and computed tomography (FDG-PET/CT) in fever of unknown origin (FUO). MATERIALS AND METHODS: Four databases were searched for studies of FDG-PET/CT in FUO 1/1/2000-1/12/2015. Exclusions were non-English language, case reports, non-standard FDG radiotracer, and significant missing data. Quality was assessed by two authors independently using a standardised tool. Pooled diagnostic yield was calculated using a random-effects model. An iterative electronic and face-to-face Delphi exercise generated interspeciality consensus. RESULTS: Pooled diagnostic yield was 56% (95% confidence interval [CI]: 50-61%, I2=61%) from 18 studies and 905 patients. Only five studies reported results of previous imaging, and subgroup analysis estimated diagnostic yield beyond conventional CT at 32% (95% CI: 22-44%; I2=66%). Consensus was established that FDG-PET/CT is increasingly available with an emerging role, but there is prevailing variability in practice. CONCLUSION: There is insufficient evidence to support the value of FDG-PET/CT in investigative algorithms of FUO. A paradigm shift in research is needed, involving prospective studies recruiting at diagnosis of FUO, with updated case definitions and hard outcome measures. Although these studies will be a significant undertaking with multicentre collaboration, their completion is vital for balancing both radiation exposure and costs against the possible benefits of utilising FDG-PET/CT.

Cell adhesion molecules as potential biomarkers of nephritis, damage and accelerated atherosclerosis in patients with SLE.

OBJECTIVES: The aim of the current study was to compare levels of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in lupus patients and controls and to investigate their association with clinical phenotype, disease activity and damage. METHODS: We compared levels of serum VCAM-1 and E-selectin in 178 female lupus patients and 69 age-and sex-matched controls. Using linear regression we also examined the association between these markers and disease activity, damage, renal and skin involvement as well as clinical and subclinical cardiovascular disease. RESULTS: E-selectin was increased in patients compared to controls (median (IQR) 10.5 (6.85, 13.9) vs 7.86 (5.39, 10.4) ng/ml; p < 0.001). E-selectin was also associated with overall damage and carotid plaque (ß (95% confidence interval): 0.27 (0.029, 0.511) and 0.26 (0.148, 0.507)). Whilst there was no significant difference in VCAM-1 levels between groups overall, we found a significant association between VCAM-1 and with active renal disease (ß (95% confidence interval): 1.10 (0.69, 1.51)). CONCLUSIONS: E-selectin may act as a marker of cardiovascular risk in SLE, whilst VCAM-1 may have a role as a non-invasive biomarker for lupus nephritis activity.

Imaging atherosclerosis in rheumatoid arthritis: evidence for increased prevalence, altered phenotype and a link between systemic and localised plaque inflammation.

In rheumatoid arthritis (RA), chronic inflammation is thought to drive increased cardiovascular risk through accelerated atherosclerosis. It may also lead to a more high-risk plaque phenotype. We sought to investigate carotid plaque phenotype in RA patients using Dynamic Contrast-Enhanced MRI (DCE-MRI) and Fludeoxyglucose Positron Emission Tomography(FDG-PET). In this pilot study, RA patients and age/sex-matched controls were evaluated for cardiovascular risk factors and carotid plaque on ultrasound. Subjects with plaque >2 mm thick underwent DCE-MRI, and a subgroup of patients had FDG-PET. Comparison of MRI findings between groups and correlation between clinical, serological markers and imaging findings was undertaken. 130 patients and 62 controls were recruited. Plaque was more prevalent in the RA group (53.1% vs 37.0%, p = 0.038) and was independently associated with IL6 levels (HR[95%CI]: 2.03 [1.26, 3.26] per quartile). DCE-MRI data were available in 15 patients and 5 controls. Higher prevalence of plaque calcification was noted in RA, despite similar plaque size (73.3% vs 20%, p = 0.04). FDG-PET detected plaque inflammation in 12/13 patients scanned and degree of inflammation correlated with hs-CRP (r = 0.58, p = 0.04). This study confirms increased prevalence of atherosclerosis in RA and provides data to support the hypothesis that patients have a high-risk plaque phenotype.