Evaluation of interleukin-6 and its soluble receptor components sIL-6R and sgp130 as markers of inflammation in inflammatory bowel diseases

Purpose

Interleukin-6 (IL-6) production and signalling are increased in the inflamed mucosa in inflammatory bowel diseases (IBD). As published serum levels of IL-6 and its soluble receptors sIL-6R and sgp130 in IBD are from small cohorts and partly contradictory, we systematically evaluated IL-6, sIL-6R and sgp130 levels as markers of disease activity in Crohn’s disease (CD) and ulcerative colitis (UC).

Methods

Consecutive adult outpatients with confirmed CD or UC were included, and their disease activity and medication were monitored. Serum from 212 CD patients (815 measurements) and 166 UC patients (514 measurements) was analysed, and 100 age-matched healthy blood donors were used as controls.

Results

IL-6 serum levels were significantly elevated in active versus inactive CD and UC, also compared with healthy controls. However, only a fraction of IBD patients showed increased serum IL-6. IL-6 levels ranged up to 32.7 ng/mL in active CD (>?5000-fold higher than in controls), but also up to 6.9 ng/mL in inactive CD. Increases in active UC (up to 195 pg/mL) and inactive UC (up to 27 pg/mL) were less pronounced. Associations between IL-6 serum levels and C-reactive protein concentrations as well as leukocyte and thrombocyte counts were observed. Median sIL-6R and sgp130 levels were only increased by up to 15%, which was considered of no diagnostic significance.

Conclusions

Only a minority of IBD patients shows elevated IL-6 serum levels. However, in these patients, IL-6 is strongly associated with disease activity. Its soluble receptors sIL-6R and sgp130 do not appear useful as biomarkers in IBD.

     

Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists

OBJECTIVE: To investigate the impact of official recommendations regarding the management of latent tuberculosis (TB) infection on the rate of active TB in patients receiving treatment with tumor necrosis factor (TNF) antagonists. METHODS: Data on active TB rates and on screening and treatment of latent TB infection were extracted from the BIOBADASER (Spanish Society of Rheumatology Database on Biologic Products), a registry of patients with rheumatic conditions treated with TNF antagonists. The rates of active TB among the BIOBADASER patients were compared with those in the background Spanish population, and BIOBADASER patients with rheumatoid arthritis (RA) were compared with a cohort of RA patients from the EMECAR (Morbidity and Clinical Expression of Rheumatoid Arthritis) study who were not treated with TNF antagonists and were followed up for 5 years. RESULTS: Active TB developed in 34 patients, of whom 32 started taking TNF antagonists prior to the official recommendations on latent TB infection (pre-OR) and 2 began treatment after the recommendations were issued (post-OR). All cases of TB occurred during treatment with infliximab, and 28 of these patients had RA. Pre-OR, the active TB rate in BIOBADASER patients was 20.9-fold higher than in the background Spanish population, while RA patients in the BIOBADASER had rates 22.6- and 6.2-fold higher than the background and EMECAR populations, respectively. Post-OR, 324 patients with a tuberculin skin test result > or =5 mm and/or chest radiograph findings suggestive of past TB were treated for 9 months with isoniazid (INH). Post-OR, active TB rates among the BIOBADASER patients decreased by 78% (incidence risk ratio [IRR] 0.22, 95% confidence interval [95% CI] 0.03-0.88; P = 0.008), while among RA patients in the BIOBADASER, the rate dropped by 83% and reached the EMECAR rate (IRR 1.0, 95% CI 0.02-8.2). There were no INH treatment-related hospitalizations or deaths. CONCLUSION: Strategies to treat latent TB infection that are tailored to the at-risk population can effectively and safely lessen the likelihood of active TB in patients treated with TNF antagonists.     

Utility of diffusion-weighted MR imaging in the diagnosis of placenta accreta spectrum abnormality

Purpose

The aim of this study was to evaluate the utility of added DWI sequences as an adjunct to traditional MR imaging in the evaluation of abnormal placentation in patients with suspicion for placenta accreta spectrum abnormality or morbidly adherent placenta (MAP).

Materials and methods

The study was approved by local ethics committee. The subjects included pregnant women with prenatal MRI performed between July 2013 to July 2015. All imaging was performed on a Philips 1.5T MR scanner using pelvic phased-array coil. Only T2-weighted and diffusion-weighted imaging (DWI) series were compiled for review. Two randomized imaging sets were created: set 1 included T2-weighted series only (T2W); set 2 included T2W with DWI series together (T2W + DWI). Three radiologists, blinded to history and pathology, reviewed the imaging, with 2 weeks of time between the two image sets. Sensitivity, specificity, and overall accuracy for MAP were calculated and compared between T2W only and T2W + DWI reads. Associations between imaging findings and invasion on pathology were tested using the Chi-squared test. Confidence scores, inter-reader agreement, and systematic differences were documented.

Results

A total of 17 pregnant women were included in the study. 8 cases were pathologically diagnosed with MAP. There were no significant differences in the diagnostic accuracy between T2W and T2W + DWI in the diagnosis of MAP in terms of overall accuracy (62.7% for T2W vs. 68.6% for T2W + DWI, p = 0.68), sensitivity (70.8% for T2W vs. 95.8% for T2W + DWI, p = 0.12), and specificity (55.6% for T2W vs. 44.4% for T2W + DWI, p = 0.49). There was no significant difference in the diagnostic confidence between the review of T2W images alone and the T2W + DWI review (mean 7.3 ± 1.8 for T2W vs. 7.5 ± 1.8 for T2W + DWI, p = 0.37).

Conclusion

With the current imaging technique, addition of DWI sequence to the traditional T2W images cannot be shown to significantly increase the accuracy or reader confidence for diagnosis of placenta accreta spectrum abnormality. However, DWI does improve identification of abnormalities in the placental–myometrial interface.

     

Test–retest reliability of the unsupported upper-limb exercise test (UULEX) and 6-min peg board ring test (6PBRT) in healthy adult individuals

Background: The unsupported upper-limb exercise (UULEX) and 6-min peg board ring tests (6PBRTs) have been developed to measure peak unsupported arm exercise capacity and arm endurance, respectively, in individuals with chronic obstructive pulmonary disease. These tests are valid and reproducible in this population; however, the reproducibility of healthy adults is currently unknown. Objective: To determine the within-day test–retest reliability of the UULEX and 6PBRT in healthy adults. Method: The study included 41 healthy adults, aged 38.3 ± 17.9 years old, who performed both tests, twice each on the same day, with a 30-min rest in between. Before and immediately after the tests, blood pressure (BP), heart rate (HR), perception of exertion, and arm fatigue were measured. Time to perform the test and number of rings moved were recorded for the UULEX and 6PBRT, respectively. Results: The UULEX was reproducible on Bland–Altman analysis with lower and upper limits of agreement: 2.40 and ?2.49 min, respectively (bias = ?0.05; p = 0.817) and intraclass correlation coefficient (ICC) = 0.85 (p < 0.0001) for time in minutes for the first and second tests. The 6PBRT was not reproducible on Bland–Altman analysis with lower and upper limits of agreement of 31.64 and ?114.54 (bias = ?41.45; p < 0.0001) and ICC = 0.91 (p < 0.0001) for the number of rings moved. Conclusion: UULEX is a reliable test in healthy adults. Only one test is adequate when measuring peak unsupported arm exercise capacity using the UULEX in healthy adults, while more than two tests may be needed to measure arm endurance using the 6PBRT.     

Milk Consumption and Mortality from All Causes,Cardiovascular Disease,and Cancer: A Systematic Review and Meta-Analysis

Results from epidemiological studies of milk consumption and mortality are inconsistent. We conducted a systematic review and meta-analysis of prospective studies assessing the association of non-fermented and fermented milk consumption with mortality from all causes, cardiovascular disease, and cancer. PubMed was searched until August 2015. A two-stage, random-effects, dose-response meta-analysis was used to combine study-specific results. Heterogeneity among studies was assessed with the I² statistic. During follow-up periods ranging from 4.1 to 25 years, 70,743 deaths occurred among 367,505 participants. The range of non-fermented and fermented milk consumption and the shape of the associations between milk consumption and mortality differed considerably between studies. There was substantial heterogeneity among studies of non-fermented milk consumption in relation to mortality from all causes (12 studies; I² = 94%), cardiovascular disease (five studies; I² = 93%), and cancer (four studies; I² = 75%) as well as among studies of fermented milk consumption and all-cause mortality (seven studies; I² = 88%). Thus, estimating pooled hazard ratios was not appropriate. Heterogeneity among studies was observed in most subgroups defined by sex, country, and study quality. In conclusion, we observed no consistent association between milk consumption and all-cause or cause-specific mortality.