Neurobiologic Features of Fibromyalgia Are Also Present Among Rheumatoid Arthritis Patients

Funding: The study recieved support from Pfizer. The funder had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript. The content is solely the responsibility of the authors. Funding Information Pfizer Aptinyx Cerephex ACKNOWLEDGEMENTS: The authors wish to thank all of the patient volunteers. We also thank Mariella D’Allesandro for supporting recruitment and data collection.Peer reviewedPostprin

PR3-ANCA:a promising biomarker in primary sclerosing cholangitis (PSC)

BACKGROUND AND AIMS:The only recognized biomarker for primary sclerosing cholangitis (PSC) is atypical anti-neutrophil cytoplasmic antibodies (aANCA), which, in addition to having low sensitivity and specificity, is an indirect immunofluorescence (IIF) test lacking the advantages of high throughput and objectivity. Recent reports have shown that antibodies to proteinase-3 (PR3-ANCA) might add diagnostic value in inflammatory bowel disease (IBD), specifically in ulcerative colitis (UC). As PSC is associated with IBD, the objective of this study was to evaluate the frequency and clinical significance of PR3-ANCA in a large cohort of patients. METHODS:A total of 244 PSC and 254 control [autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), hepatitis C viral infection (HCV), hepatitis B viral infection (HBV), and healthy controls] sera and their clinical correlations were retrospectively analyzed for PR3-ANCA determined by ELISA and a new chemiluminescence immunoassay (CIA). Testing was also performed for aANCA by IIF. RESULTS:When measured by CIA, PR3-ANCA was detected in 38.5% (94/244) of PSC patients compared to 10.6% (27/254) controls (p<0.0001). By ELISA, PR3-ANCA was detected in 23.4% (57/244) of PSC patients compared to 2.7% (6/254) controls (p<0.0001). PR3-ANCA in PSC patients was not associated with the presence or type of underlying IBD, and, in fact, it was more frequent in Crohn's disease (CD) patients with PSC than previously reported in CD alone. PR3-ANCA in PSC measured by CIA correlated with higher liver enzymes. CONCLUSION:PR3-ANCA is detected in a significant proportion of PSC patients compared to other liver diseases including PBC and AIH. PR3-ANCA is associated with higher liver enzyme levels in PSC, and is not solely related to underlying IBD

Top down or bottom up? An observational investigation of improvement in fibromyalgia symptoms following hip and knee replacement

Objectives: Many patients with osteoarthritis have comorbid symptoms of FM, but it is unknown how these symptoms respond to surgical procedures that address nociceptive input in the periphery, such as total joint replacement. Here we explore differences in clinical characteristics between patients whose FM symptoms do and do not improve following total hip or knee replacement. Methods: Participants were 150 patients undergoing knee or hip replacement who had a minimum FM survey score of 4 or greater prior to surgery. The top tertile of patients experiencing the most improvement in FM symptoms at month 6 were categorized as ‘Improve’ (n = 48) while the bottom two tertiles were categorized as ‘Worsen/Same’ (n = 102). Baseline symptom characteristics were compared between groups, as well as improvement in overall pain severity, surgical pain severity and physical function at 6 months. Results: The Worsen/Same group had higher levels of fatigue, depression and surgical site pain at baseline (all P &lt; 0.05). Additionally, they improved less on overall pain severity and physical functioning 6 months after surgery (both P &lt; 0.05). Conclusion: Most patients derive significant benefit in improvement of comorbid FM symptoms following total joint replacement, but a substantial proportion do not. Understanding the neurobiological basis for these different trajectories may help inform clinical judgment and improve patient care

A multi-modal MRI study of the central response to inflammation in rheumatoid arthritis

Special thanks to the patient community who participated in this research effort. Thanks to Mariella D’Allesandro for efforts towards recruitment.Peer reviewedPublisher PD

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

Functional Brain Network Mechanism of Fibromyalgia Hypersensitivity

2

Functional Brain Network Mechanism of Hypersensitivity in Chronic Pain

Abstract Fibromyalgia (FM) is a chronic widespread pain condition characterized by augmented multi-modal sensory sensitivity. Although the mechanisms underlying this sensitivity are thought to involve an imbalance in excitatory and inhibitory activity throughout the brain, the underlying neural network properties associated with hypersensitivity to pain stimuli are largely unknown. In network science, explosive synchronization (ES) was introduced as a mechanism of hypersensitivity in diverse biological and physical systems that display explosive and global propagations with small perturbations. We hypothesized that ES may also be a mechanism of the hypersensitivity in FM brains. To test this hypothesis, we analyzed resting state electroencephalogram (EEG) of 10 FM patients. First, we examined theoretically well-known ES conditions within functional brain networks reconstructed from EEG, then tested whether a brain network model with ES conditions identified in the EEG data is sensitive to an external perturbation. We demonstrate for the first time that the FM brain displays characteristics of ES conditions, and that these factors significantly correlate with chronic pain intensity. The simulation data support the conclusion that networks with ES conditions are more sensitive to perturbation compared to non-ES network. The model and empirical data analysis provide convergent evidence that ES may be a network mechanism of FM hypersensitivity

Functional and structural magnetic resonance imaging correlates of fatigue in patients with rheumatoid arthritis

The authors wish to thank all of the patient volunteers. We also thank Mariella D’Allesandro for supporting recruitment and data collection. N.B., C.M.K., E.I., A.S., T.L., G.W., A.M., R.E.H. and D.J.C. were involved in designing the study and interpreting the data, drafting the article and revising it critically for important intellectual content. All authors approved the final version to be published. N.B. and C.M.K. analysed the data, and N.B. and R.E.H. wrote the first draft. E.I., T.L. and G.W. contributed to the data analysis. N.B. had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Funding: This work was supported by Pfizer. The funder had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript. The content is solely the responsibility of the authors.Peer reviewedPostprin

Association of Inflammation With Pronociceptive Brain Connections in Rheumatoid Arthritis Patients With Concomitant Fibromyalgia

Financial Support: This study was supported by Pfizer. Acknowledgements: Special thanks to the patients who volunteered to be part of this research effort and thank you to Mariella D’Allesandro for help with recruitment and data collection.Peer reviewedPostprin

Greater Somatosensory Afference With Acupuncture Increases Primary Somatosensory Connectivity and Alleviates Fibromyalgia Pain via Insular γ‐Aminobutyric Acid: A Randomized Neuroimaging Trial

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/168243/1/art41620.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/168243/2/art41620_am.pd