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Arthritis Research & Therapy Feb 2022Based on clinical and genetic associations, axial spondyloarthritis (axSpA) and inflammatory bowel disease (IBD) are suspected to have a linked pathogenesis. Gut...
BACKGROUND
Based on clinical and genetic associations, axial spondyloarthritis (axSpA) and inflammatory bowel disease (IBD) are suspected to have a linked pathogenesis. Gut dysbiosis, intrinsic to IBD, has also been observed in axSpA. It is, however, not established to what degree gut dysbiosis is associated with axSpA disease severity. The objective of this study was to compare gut dysbiosis frequency between controls, non-radiographic axial spondyloarthritis (nr-axSpA), and ankylosing spondylitis (AS) patients and investigate whether gut dysbiosis is cross-sectionally associated with axSpA disease activity, physical function, mobility, or pain.
METHODS
Gut dysbiosis was assessed by 16SrRNA analysis of feces from 44/88 nr-axSpA/AS patients (ASAS/mNY criteria) without inflammatory bowel disease (IBD) and 46 controls without IBD or rheumatic disease. The GA-map™ Dysbiosis Test was used, grading gut microbiota aberrations on a 1-5 scale, where ≥3 denotes dysbiosis. Proportions with dysbiosis were compared between the groups. Furthermore, standard axSpA measures of disease activity, function, mobility, and pain were compared between patients (nr-axSpA and AS combined) with and without dysbiosis, univariately, and adjusted for relevant confounders (ANCOVA).
RESULTS
Gut dysbiosis was more frequent in AS than controls (36% versus 17%, p=0.023), while nr-axSpA (25% dysbiosis) did not differ significantly from either AS or controls. Univariately, most axSpA measures were significantly worse in patients with dysbiosis versus those without: ASDAS-CRP between-group difference 0.6 (95% CI 0.2-0.9); BASDAI 1.6 (0.8-2.4); evaluator's global disease activity assessment (Likert scale 0-4) 0.3 (0.1-0.5), BASFI 1.5 (0.6-2.4), and VAS pain (cm) 1.3 (0.4-2.2). Differences remained significant after adjustment for demographics, lifestyle factors, treatments, gut inflammation (fecal calprotectin ≥50 mg/kg), and gut symptoms, except for VAS pain. BASMI and CRP were not associated with dysbiosis.
CONCLUSION
Gut dysbiosis, more frequent in AS patients than controls, is associated with worse axSpA disease activity and physical function, seemingly irrespective of both gut inflammation and treatments. This provides further evidence for an important link between disturbances in gastrointestinal homeostasis and axSpA.
Topics: Axial Spondyloarthritis; Dysbiosis; Humans; Leukocyte L1 Antigen Complex; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 35151357
DOI: 10.1186/s13075-022-02733-w -
Acta Reumatologica Portuguesa 2021Axial Spondyloarthritis (axSpA) is a chronic, inflammatory rheumatic disease that affects the axial skeleton, causing pain, stiffness, and fatigue. Genetics and...
BACKGROUND
Axial Spondyloarthritis (axSpA) is a chronic, inflammatory rheumatic disease that affects the axial skeleton, causing pain, stiffness, and fatigue. Genetics and environmental factors such as microbiota and microtrauma are known causes of disease susceptibility and progression. Murine models of axSpA found a decisive role for biomechanical stress as an inducer of enthesitis and new bone formation. Here, we hypothesize that muscle properties in axSpA patients are compromised and influenced by genetic background.
OBJECTIVES
To improve our current knowledge of axSpA physiopathology, we aim to characterize axial and peripheral muscle properties and identify genetic and protein biomarker that might explain such properties.
METHODS
A cross-sectional study will be conducted on 48 participants aged 18-50 years old, involving patients with axSpA (according to ASAS classification criteria, symptoms duration < 10 years) and healthy controls matched by gender, age, and levels of physical activity. We will collect epidemiological and clinical data and perform a detailed, whole body and segmental, myofascial characterization (focusing on multifidus, brachioradialis and the gastrocnemius lateralis) concerning: a) Physical Properties (stiffness, tone and elasticity), assessed by MyotonPRO®; b) Strength, by a dynamometer; c) Mass, by bioimpedance; d) Performance through gait speed and 60-second sit-to-stand test; e) Histological and cellular/ molecular characterization through ultrasound-guided biopsies of multifidus muscle; f) Magnetic Resonance Imaging (MRI) characterization of paravertebral muscles. Furthermore, we will perform an integrated transcriptomics and proteomics analysis of peripheral blood samples.
DISCUSSION
The innovative and multidisciplinary approaches of this project rely on the elucidation of myofascial physical properties in axSpA and also on the establishment of a biological signature that relates to specific muscle properties. This hitherto unstudied link between gene/protein signatures and muscle properties may enhance our understanding of axSpA physiopathology and reveal new and useful diagnostic and therapeutic targets.
Topics: Adolescent; Adult; Animals; Axial Spondyloarthritis; Cross-Sectional Studies; Humans; Mice; Middle Aged; Muscles; Spondylarthritis; Spondylitis, Ankylosing; Young Adult
PubMed: 34962249
DOI: No ID Found -
Arthritis Research & Therapy Oct 2019Patients with ankylosing spondylitis (AS) have a higher prevalence of depression compared to the general population. Comorbid depression in AS likely has a...
BACKGROUND
Patients with ankylosing spondylitis (AS) have a higher prevalence of depression compared to the general population. Comorbid depression in AS likely has a multifactorial origin. While several disease-related and contextual factors have been associated with depressive symptoms in AS, a comprehensive model of their interrelations is currently lacking. Such a model could help understand the mechanisms leading to, or maintaining, depression in AS. The objectives of the current study were to determine which factors are associated with depressive symptoms in AS and to understand their underlying relationships.
METHODS
Data from a cross-sectional survey-based multicentre study were used. Potential determinants included both contextual and disease-related factors. Depressive symptoms were assessed by the Hospital Anxiety and Depression Subscale (HADS-D). Direct and indirect associations between risk factors and the latent depressive symptom outcome were explored using structural equation modelling. A final model was selected based on model fit criteria and clinical plausibility.
RESULTS
Among 245 patients, median HADS-D score was 3 (interquartile range 1-6), and 44 patients (18%) had a HADS-D score ≥ 8, indicating possible depression. In the final model, contextual factors significantly associated with depressive symptoms were male gender, being employed, lower income, lower mastery and worse satisfaction with social role participation. Bath AS Disease Activity Index (BASDAI) was the only disease-related factor that was associated with depressive symptoms, acted only indirectly via mastery, and its standardized total effect on depressive symptoms was smaller than that of several contextual factors. Mastery had a central role in the path diagram and mediated the effects of BASDAI, income and satisfaction with social role participation on depressive symptoms. The final model explained 64% of the variance in the depression outcome.
CONCLUSIONS
Both contextual and disease-related factors are associated with depressive symptoms in AS. Mastery, the extent to which one feels in control over life and disease, has a key role in this process. Results support a relevance of self-efficacy in disease management and patient education. In order to improve patients' mental health, research is warranted whether mastery and its relation with depression can be modified.
Topics: Adult; Cross-Sectional Studies; Depression; Female; Humans; Male; Middle Aged; Models, Theoretical; Spondylitis, Ankylosing; Surveys and Questionnaires
PubMed: 31639012
DOI: 10.1186/s13075-019-1995-7 -
Proceedings of the Royal Society of... Mar 1967
Topics: Adult; Aged; Ankylosis; Arthritis, Rheumatoid; Arthrodesis; Arthroplasty; Female; Hip Joint; Humans; Middle Aged; Prostheses and Implants
PubMed: 6020156
DOI: No ID Found -
Indian Journal of Dental Research :... 2017Temporomandibular joint (TMJ) ankylosis is a situation in which the mandibular condyle is fused to the glenoid fossa by bone or fibrous tissue. The management of TMJ...
BACKGROUND
Temporomandibular joint (TMJ) ankylosis is a situation in which the mandibular condyle is fused to the glenoid fossa by bone or fibrous tissue. The management of TMJ ankylosis has a complicated chore, and it is challenging for the maxillofacial surgeon because of technical hitches and high rate of reankylosis. Costochondral graft (CCG) is a common treatment modality for TMJ ankylosis. One of disadvantages of CCG is unpredictability of growth pattern and risk of overgrowth. This report illustrates the fate of CCG used in the TMJ reconstruction and also the management of patients with CCG overgrowth.
MATERIALS AND METHODS
A retrospective evaluation of 14 patients presented with unilateral TMJ ankylosis reconstructed using CCG treated in our hospital from 2000 to 2013 was done. Only patients with unilateral ankylosis treated by CCG with at least 2-year follow-up and complete case records with clinical and radiographic details were included in the study. Patients with bilateral ankylosis, reankylosis, missing details, and the patients with <2-year follow-up were excluded from the study. The patients were selected based on the specified inclusion/exclusion criteria. All the patients were analyzed clinically and radiographically. Facial appearance, jaw motion, occlusion, contour, and linear growth changes were documented preoperatively, immediately postoperatively, and long term (>2 years).
RESULTS
Totally 14 unilateral temporomandibular ankylosis cases were reconstructed using CCG from the period of 2000-2013. The mean age of the patients is 5.2 years with the standard deviation of 1.48 ranging from 3 to 9 years. Follow-up of the patients ranges from 2 to 6 years with mean follow-up of 3 years. Out of 14 patients, 2 patients had normal growth of CCG after the mean follow-up of 3 years, whereas 5 patients presented with moderate growth, 4 patients with CCG overgrowth, and 3 patients presented with no growth of CCG following surgery. Overgrown CCG was treated with condylar shaving, and orthodontic elastic was maintained to stabilize the occlusion. Moderately grown and nongrowing CCG was treated by internal distractor for the management of facial symmetry. Facial asymmetry and malocclusion were successfully corrected in all patients with altered growth pattern.
CONCLUSION
The growth pattern of the CCG is extremely unpredictable, which can be in the form of no growth at all or excessive growth, and mandibular overgrowth on the grafted site can actually be more troublesome than the lack of growth. Care should also be taken to ensure proper postoperative functional therapy and to examine the role of cartilage thickness on future growth in young patients.
Topics: Ankylosis; Cartilage; Child; Child, Preschool; Female; Humans; Hyperostosis; Male; Mandibular Reconstruction; Postoperative Complications; Retrospective Studies; Temporomandibular Joint Disorders; Treatment Outcome
PubMed: 28611327
DOI: 10.4103/ijdr.IJDR_141_17 -
BMC Oral Health Dec 2021Traumatic haemarthrosis was hypothesized to be the etiology of temporomandibular (TMJ) ankylosis. Here, taking haematoma absorbance as a control, we aimed to reveal the...
BACKGROUND
Traumatic haemarthrosis was hypothesized to be the etiology of temporomandibular (TMJ) ankylosis. Here, taking haematoma absorbance as a control, we aimed to reveal the molecular mechanisms involved in haematoma organizing into ankylosis using transcriptome microarray profiles.
MATERIAL/METHODS
Disk removal was performed to building haematoma absorbance (HA) in one side of TMJ, while removal of disk and articular fibrous layers was performed to induced TMJ ankylosis through haematoma organization (HO) in the contralateral side in a sheep model. Haematoma tissues harvested at days 1, 4 and 7 postoperatively were examined by histology, and analyzed by Affymetrix OviGene-1_0-ST microarrays. The DAVID were recruited to perform the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis for the different expression genes (DEGs). The DEGs were also typed into protein-protein interaction (PPI) networks to get the interaction data. Six significant genes screened from PPI analysis, were confirmed by real-time PCR.
RESULTS
We found 268, 223 and 17 DEGs at least twofold at days 1, 4 and 7, respectively. At day 1, genes promoting collagen ossification (POSTN, BGN, LUM, SPARC), cell proliferation (TGF-β), and osteogenic differentiation of mesenchymal stem cells (BMP-2) were up-regulated in the HO side. At day 4, several genes involved in angiogenesis (KDR, FIT1, TEK) shower higher expression in the HO side. While HA was characterized by a continuous immune and inflammatory reaction.
CONCLUSIONS
Our results provide a comprehensive understanding of the role of haematoma in the onset and progress of TMJ ankylosis. The study will contribute to explaining why few injured TMJs ankylose and most do not from the molecular level.
Topics: Animals; Ankylosis; Hemarthrosis; Mandibular Condyle; Microarray Analysis; Osteogenesis; Sheep; Temporomandibular Joint
PubMed: 34961493
DOI: 10.1186/s12903-021-02033-w -
Frontiers in Immunology 2022Ankylosing spondylitis (AS) is an immune-mediated inflammatory disorder that primarily affects the axial skeleton, especially the sacroiliac joints and spine. This...
Ankylosing spondylitis (AS) is an immune-mediated inflammatory disorder that primarily affects the axial skeleton, especially the sacroiliac joints and spine. This results in chronic back pain and, in extreme cases, ankylosis of the spine. Despite its debilitating effects, the pathogenesis of AS remains to be further elucidated. This study used single cell CITE-seq technology to analyze peripheral blood mononuclear cells (PBMCs) in AS and in healthy controls. We identified a number of molecular features associated with AS. CD52 was found to be overexpressed in both RNA and surface protein expression across several cell types in patients with AS. CD16 monocytes overexpressed and IL-18Rα in AS, while CD8 T cells and natural killer cells overexpressed genes linked with cytotoxicity, including , and . Tregs underexpressed CD39 in AS, suggesting reduced functionality. We identified an overrepresented NK cell subset in AS that overexpressed CD16, CD161, and CD38, as well as cytotoxic genes and pathways. Finally, we developed machine learning models derived from CITE-seq data for the classification of AS and achieved an Area Under the Receiver Operating Characteristic (AUROC) curve of > 0.95. In summary, CITE-seq identification of AS-associated genes and surface proteins in specific cell subsets informs our understanding of pathogenesis and potential new therapeutic targets, while providing new approaches for diagnosis machine learning.
Topics: Epitopes; Humans; Leukocytes, Mononuclear; Machine Learning; Spondylitis, Ankylosing; Transcriptome
PubMed: 35634297
DOI: 10.3389/fimmu.2022.838636 -
The European Journal of Health... Nov 2022Preference-based health-state utility values (HSUVs), such as the EuroQol five-dimensional questionnaire (EQ-5D-5L), are needed to calculate quality-adjusted life-years...
BACKGROUND
Preference-based health-state utility values (HSUVs), such as the EuroQol five-dimensional questionnaire (EQ-5D-5L), are needed to calculate quality-adjusted life-years (QALYs) for cost-effectiveness analyses. However, these are rarely used in clinical trials of interventions in axial spondyloarthritis (axSpA). In these cases, mapping can be used to predict HSUVs.
OBJECTIVE
To develop mapping algorithms to estimate EQ-5D-5L HSUVs from the Bath Ankylosing Disease Activity Index (BASDAI) and the Bath Ankylosing Spondylitis Functional Index (BASFI).
METHODS
Data from the British Society for Rheumatology Biologics Register in Ankylosing Spondylitis (BSRBR-AS) provided 5122 observations with complete BASDAI, BASFI, and EQ-5D-5L responses covering the full range of disease severity. We compared direct mapping using adjusted limited dependent variable mixture models (ALDVMMs) and optional inclusion of the gap between full health and the next feasible value with indirect response mapping using ordered probit (OPROBIT) and generalised ordered probit (GOPROBIT) models. Explanatory variables included BASDAI, BASFI, and age. Metrics to assess model goodness-of-fit and performance/accuracy included Akaike and Bayesian information criteria (AIC/BIC), mean absolute error (MAE) and root mean square error (RMSE), plotting predictive vs. observed estimates across the range of BASDAI/BASFI and comparing simulated data with the original data set for the preferred/best model.
RESULTS
Overall, the ALDVMM models that did not formally include the gap between full health and the next feasible value outperformed those that did. The four-component mixture models (with squared terms included) performed better than the three-component models. Response mapping using GOPROBIT (no squared terms included) or OPROBIT (with squared terms included) offered the next best performing models after the three-component ALDVMM (with squared terms). Simulated data of the preferred model (ALDVMM with four-components) did not significantly underestimate uncertainty across most of the range of EQ-5D-5L values, however the proportion of data at full health was underrepresented, likely due in part to model fitting on a small number of observations at this point in the actual data (4%).
CONCLUSIONS
The mapping algorithms developed in this study enabled the generation of EQ-5D-5L utilities from BASDAI/BASFI. The indirect mapping equations reported for the EQ-5D-5L facilitate the calculation of the EQ-5D-5L utility scores using other UK and country-specific value sets.
Topics: Axial Spondyloarthritis; Bayes Theorem; Biological Products; Humans; Quality of Life; Registries; Spondylitis, Ankylosing; Surveys and Questionnaires; United Kingdom
PubMed: 35113270
DOI: 10.1007/s10198-022-01429-x -
Current Opinion in Rheumatology Jul 2013To review the optimal criteria and conditions for establishing a clinical registry, as well as detailing their application in a number of ankylosing spondylitis (AS) and... (Review)
Review
PURPOSE OF REVIEW
To review the optimal criteria and conditions for establishing a clinical registry, as well as detailing their application in a number of ankylosing spondylitis (AS) and axial spondyloarthritis (axSpA) Registries already in existence.
RECENT FINDINGS
Recent genetic studies and studies of long-term treatment efficacy and side-effects have underscored the need for large numbers of patients, much larger than would be possible from a single center or consortium. An optimal Registry should have its aims established upfront, with appropriate governance and oversight, and inclusion and exclusion criteria for participating collaborators and subject defined. Collaborators contributing subjects to a Registry should use validated instruments for which they have been previously trained. The numerous cross-sectional and longitudinal Registries on AS and axSpA have been recently established that differ widely depending on the referral and selection issues.
SUMMARY
The challenge of large-scale examinations of genetics, comorbidities, medication usage, and side-effects in spondyloarthritis underscores the need for combining data from well characterized registries of AS patients which require careful planning. There are currently many such registries available internationally, offering promise for collaborations and data pooling that can answer some of the pressing questions facing rheumatology clinicians and researchers.
Topics: Humans; International Cooperation; Prevalence; Registries; Spondylitis, Ankylosing; Treatment Outcome
PubMed: 23656716
DOI: 10.1097/BOR.0b013e3283620e1d -
Reumatologia Clinica 2021To reach a consensus on the tools available to evaluate disease activity in patients with axial spondyloarthritis (axSpA), and to develop a consensus definition of...
OBJECTIVE
To reach a consensus on the tools available to evaluate disease activity in patients with axial spondyloarthritis (axSpA), and to develop a consensus definition of remission in axSpA.
METHODS
A modified Delphi method was used. A scientific committee proposed statements addressing the assessment of axSpA in clinical practice and the definition of remission. The questionnaire was evaluated in 2 rounds by rheumatologists from GRESSER (GRupo de Estudio de ESpondiloartritis de la Sociedad Española de Reumatología).
RESULTS
After 2 rounds of evaluation, a panel of 81 rheumatologists reached agreement on 56 out of the 80 proposed items (72.0%). There was agreement that the definition of remission in axSpA should include: disease activity, pain, fatigue, peripheral involvement, extra-articular manifestations, laboratory tests, functional impairment, mobility, quality of life, need for treatment, radiographic progression, and patient and physician global assessments. It is recommended to set a therapeutic goal when starting a treatment. The ideal goal is remission although low disease activity may also be an acceptable alternative. The Ankylosing Spondylitis Disease Activity Score (ASDAS) is the preferred tool to assess disease activity. The panel made a proposal for clinical remission in axSpA based on the ASDAS cut-off value for inactive disease, the absence of extra-articular (acute anterior uveitis, psoriasis, inflammatory bowel disease) and peripheral (arthritis, enthesitis, dactylitis) manifestations, plus normal C-reactive protein levels and absence of radiographic progression.
CONCLUSION
This work offers consensus recommendations and a proposal of clinical remission that may be useful in the management of patients with axSpA.
Topics: Axial Spondyloarthritis; Consensus; Humans; Quality of Life; Spondylarthritis; Spondylitis, Ankylosing
PubMed: 34301380
DOI: 10.1016/j.reumae.2020.01.008