Plasma interferon-alpha is associated with double-positivity for autoantibodies but is not a predictor of remission in early rheumatoid arthritis-a spin-off study of the NORD-STAR randomized clinical trial

BACKGROUND: The type I interferon (IFN) gene signature is present in a subgroup of patients with early rheumatoid arthritis (RA). Protein levels of IFNα have not been measured in RA and it is unknown whether they associate with clinical characteristics or treatment effect. METHODS: Patients with early untreated RA (n = 347) were randomized to methotrexate combined with prednisone, certolizumab-pegol, abatacept, or tocilizumab. Plasma IFNα protein levels were determined by single molecular array (Simoa) before and 24 weeks after treatment initiation and were related to demographic and clinical factors including clinical disease activity index, disease activity score in 28 joints, swollen and tender joint counts, and patient global assessment. RESULTS: IFNα protein positivity was found in 26% of the patients, and of these, 92% were double-positive for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). IFNα protein levels were reduced 24 weeks after treatment initiation, and the absolute change was similar irrespective of treatment. IFNα protein positivity was associated neither with disease activity nor with achievement of CDAI remission 24 weeks after randomization. CONCLUSION: IFNα protein positivity is present in a subgroup of patients with early RA and associates with double-positivity for autoantibodies but not with disease activity. Pre-treatment IFNα positivity did not predict remission in any of the treatment arms, suggesting that the IFNα system is distinct from the pathways of TNF, IL-6, and T-cell activation in early RA. A spin-off study of the NORD-STAR randomized clinical trial, NCT01491815 (ClinicalTrials), registered 12/08/2011, https://clinicaltrials.gov/ct2/show/NCT01491815

Quantification and visualization of cardiovascular 4D velocity mapping accelerated with parallel imaging or k-t BLAST: head to head comparison and validation at 1.5 T and 3 T

<p>Abstract</p> <p>Background</p> <p>Three-dimensional time-resolved (4D) phase-contrast (PC) CMR can visualize and quantify cardiovascular flow but is hampered by long acquisition times. Acceleration with SENSE or k-t BLAST are two possibilities but results on validation are lacking, especially at 3 T. The aim of this study was therefore to validate quantitative in vivo cardiac 4D-acquisitions accelerated with parallel imaging and k-t BLAST at 1.5 T and 3 T with 2D-flow as the reference and to investigate if field strengths and type of acceleration have major effects on intracardiac flow visualization.</p> <p>Methods</p> <p>The local ethical committee approved the study. 13 healthy volunteers were scanned at both 1.5 T and 3 T in random order with 2D-flow of the aorta and main pulmonary artery and two 4D-flow sequences of the heart accelerated with SENSE and k-t BLAST respectively. 2D-image planes were reconstructed at the aortic and pulmonary outflow. Flow curves were calculated and peak flows and stroke volumes (SV) compared to the results from 2D-flow acquisitions. Intra-cardiac flow was visualized using particle tracing and image quality based on the flow patterns of the particles was graded using a four-point scale.</p> <p>Results</p> <p>Good accuracy of SV quantification was found using 3 T 4D-SENSE (r²= 0.86, -0.7 ± 7.6%) and although a larger bias was found on 1.5 T (r²= 0.71, -3.6 ± 14.8%), the difference was not significant (p = 0.46). Accuracy of 4D k-t BLAST for SV was lower (p < 0.01) on 1.5 T (r²= 0.65, -15.6 ± 13.7%) compared to 3 T (r²= 0.64, -4.6 ± 10.0%). Peak flow was lower with 4D-SENSE at both 3 T and 1.5 T compared to 2D-flow (p < 0.01) and even lower with 4D k-t BLAST at both scanners (p < 0.01). Intracardiac flow visualization did not differ between 1.5 T and 3 T (p = 0.09) or between 4D-SENSE or 4D k-t BLAST (p = 0.85).</p> <p>Conclusions</p> <p>The present study showed that quantitative 4D flow accelerated with SENSE has good accuracy at 3 T and compares favourably to 1.5 T. 4D flow accelerated with k-t BLAST underestimate flow velocities and thereby yield too high bias for intra-cardiac quantitative in vivo use at the present time. For intra-cardiac 4D-flow visualization, however, 1.5 T and 3 T as well as SENSE or k-t BLAST can be used with similar quality.</p

The effect of immunomodulators on the immunogenicity of TNF-blocking therapeutic monoclonal antibodies: a review

Therapeutic monoclonal antibodies have revolutionized the treatment of various inflammatory diseases. Immunogenicity against these antibodies has been shown to be clinically important: it is associated with shorter response duration because of diminishing concentrations in the blood and with infusion reactions. Concomitant immunomodulators in the form of methotrexate or azathioprine reduced the immunogenicity of therapeutic antibodies in rheumatoid arthritis, Crohn disease, and juvenile idiopathic arthritis. The occurrence of adverse events does not increase when immunomodulators are added to therapeutic antibodies. The mechanism whereby methotrexate and azathioprine influence immunogenicity remains unclear. Evidence-based consensus on prescribing concomitant immunomodulators is needed

Large-scale, prospective, observational studies in patients with psoriasis and psoriatic arthritis: A systematic and critical review

<p>Abstract</p> <p>Background</p> <p>Observational studies, if conducted appropriately, play an important role in the decision-making process providing invaluable information on effectiveness, patient-reported outcomes and costs in a real-world environment. We conducted a systematic review of large-scale, prospective, cohort studies with the aim of (a) summarising design characteristics, the interventions or aspects of the disease studied and the outcomes measured and (b) investigating methodological quality.</p> <p>Methods</p> <p>We included prospective, cohort studies which included at least 100 adults with psoriasis or psoriatic arthritis. Studies were identified through searches in electronic databases (Pubmed, Medline, Cochrane library, Centre for Reviews and Dissemination). Information on study characteristics were extracted and tabulated and quality assessment, using a checklist of 18 questions, was conducted.</p> <p>Results</p> <p>Thirty five papers covering 16 cohorts met the inclusion criteria. There were ten treatment-related studies, only two of which provided a comparison between treatments, and six non-treatment studies which examined a number of characteristics of the disease including mortality, morbidity, cost of illness and health-related quality of life. All studies included a clinical outcome measure and 11 included patient-reported outcomes, however only two studies reported information on patient utilities and two on costs. The quality of the assessed studies varied widely. Studies did well on a number of quality assessment questions including having clear objectives, documenting selection criteria, providing a representative sample, defining interventions/characteristics under study, defining and using appropriate outcomes, describing results clearly and using appropriate statistical tests. The quality assessment criteria least adhered to involved questions regarding sample size calculations, describing potential selection bias, defining and adjusting for confounders and losses to follow-up, and defining and describing a comparison group.</p> <p>Conclusion</p> <p>The review highlights the need for well designed prospective observational studies on the effectiveness, patient-reported outcomes and economic impact of treatment regimes for patients with psoriasis and psoriatic arthritis in a real-world environment.</p

Adenocarcinoma arising in a cystic duplication of the small bowel: case report and review of literature

Enteric duplications are rare, but can occur anywhere along the digestive tract. Most of the patients become symptomatic in early childhood and only a few cases of adult patients have been reported in literature. Here we report a unique case of an adenocarcinoma arising in a coincidentally found cystic duplication of the small bowel

Toward a Comprehensive Approach to the Collection and Analysis of Pica Substances, with Emphasis on Geophagic Materials

Pica, the craving and subsequent consumption of non-food substances such as earth, charcoal, and raw starch, has been an enigma for more than 2000 years. Currently, there are little available data for testing major hypotheses about pica because of methodological limitations and lack of attention to the problem.In this paper we critically review procedures and guidelines for interviews and sample collection that are appropriate for a wide variety of pica substances. In addition, we outline methodologies for the physical, mineralogical, and chemical characterization of these substances, with particular focus on geophagic soils and clays. Many of these methods are standard procedures in anthropological, soil, or nutritional sciences, but have rarely or never been applied to the study of pica.Physical properties of geophagic materials including color, particle size distribution, consistency and dispersion/flocculation (coagulation) should be assessed by appropriate methods. Quantitative mineralogical analyses by X-ray diffraction should be made on bulk material as well as on separated clay fractions, and the various clay minerals should be characterized by a variety of supplementary tests. Concentrations of minerals should be determined using X-ray fluorescence for non-food substances and inductively coupled plasma-atomic emission spectroscopy for food-like substances. pH, salt content, cation exchange capacity, organic carbon content and labile forms of iron oxide should also be determined. Finally, analyses relating to biological interactions are recommended, including determination of the bioavailability of nutrients and other bioactive components from pica substances, as well as their detoxification capacities and parasitological profiles.This is the first review of appropriate methodologies for the study of human pica. The comprehensive and multi-disciplinary approach to the collection and analysis of pica substances detailed here is a necessary preliminary step to understanding the nutritional enigma of non-food consumption