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Background: Radiographic axial spondyloarthritis (r-axSpA), formerly known as ankylosing spondylitis (AS), is a chronic, inflammatory rheumatic disease associated with symptoms such as inflammatory back pain, morning stiffness, and arthritis. First-line recommendations for patients with AS include treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) for reducing pain and stiffness. Objectives: The objective of our study is to evaluate the efficacy and short-term NSAID-sparing effect of secukinumab in patients with AS currently treated with NSAIDs. Design: We assessed the clinical Assessment of SpondyloArthritis International Society (ASAS20) response to secukinumab and evaluated the extent to which the use of concomitant NSAID can be reduced between weeks 4 and 12 in r-axSpA patients treated with secukinumab 150 mg compared with placebo. Methods: ASTRUM was a prospective 24-week randomized controlled trial of adult patients with active r-axSpA [Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ⩾4] who had a documented inadequate response to ⩾2 NSAIDs. Patients were randomized (1:1:1) to initiate treatment with subcutaneous secukinumab 150 mg from either week 0 (group 1), week 4 (group 2), or week 16 (group 3). From week 4 onward, tapering of NSAIDs was allowed in all groups. Results: This study included 211 patients (n = 71, 70, and 70 in groups 1, 2, and 3, respectively). ASAS20 response at week 12 for pooled groups 1 and 2 versus group 3 was 51.1% versus 44.3% (p = 0.35). A higher proportion of patients in groups 1 and 2 achieved ASAS40 and BASDAI50 and showed improvements in other secondary clinical outcomes as compared to group 3 at week 16. More patients in groups 1 and 2 versus group 3 stopped their NSAID intake from baseline through week 16. Conclusion: Treatment with secukinumab improved clinical outcomes and showed a short-term NSAID-sparing effect in patients with r-axSpA, even though the primary endpoint was not met. Trial registration: ClinicalTrials.gov; NCT02763046, EudraCT 2015-004575-74.
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The city and casino of Wiesbaden, capital of the German state Hessen, have endowed the Carol Nachman Prize to promote research work in the field of rheumatology since 1972. The prize, endowed with 37,500â¯, is the second highest medical award in Germany and serves to promote clinical, therapeutic, and experimental research work in the field of rheumatology. In June 2022, the 50-year anniversary was celebrated. In the symposium preceding the award ceremony, an overview was given on the significance of spondyloarthritis for the work of the awardees in the past 30 years. This overview has now been put together to inform the interested community of the work performed, including the opinion of the awardees regarding what they consider to be their most important contribution.
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OBJECTIVES: To assess the association of posterior element (PE) and facet joint (FJ) inflammation with subsequent new FJ ankylosis (FJA) on MRI, in patients with radiographic axial spondyloarthritis (r-axSpA). METHODS: Patients from the Sensitive Imaging in Ankylosing Spondylitis cohort, inclusion criteria r-axSpA and ≥1 radiographic spinal syndesmophyte, were studied. MRI of the full spinal was performed at baseline, 1 and 2 years. PE/FJ inflammatory lesions and FJA were assessed per vertebral unit (VU) level by three readers. With multilevel time-lagged autoregressive generalised estimated equations, the association between PE/FJ inflammation and the subsequent development of FJA was investigated, taking the reader and VU levels into account. RESULTS: Out of the 58 patients with at least 2 reader scores available, mean age 49 (SD 10) years, 84% men, 59% had baseline PE inflammation, 24% had FJ inflammation and 26% had FJA. PE inflammation was more prevalent in the lower thoracic spine and FJ inflammation in the upper thoracic spine. VU with PE or FJ inflammation showed subsequent new FJA in two and one VU levels, respectively. The probability of developing FJA doubled with prior FJ inflammation. In multilevel analysis, FJ inflammation was associated with subsequent FJA (OR=3.8, 95% CI: 1.5 to 9.8), while no association was found between PE inflammation and new FJA (OR=1.2 (0.6-2.4)). CONCLUSIONS: FJ inflammation is rare in severe r-axSpA, but when present, the likelihood of developing subsequent FJA is over three times higher compared with FJ without inflammation. This finding contributes to the understanding of the relationship between inflammation and ankylosis at the same anatomical location in patients with axSpA.
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Anquilose , Espondiloartrite Axial , Inflamação , Imageamento por Ressonância Magnética , Articulação Zigapofisária , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Anquilose/etiologia , Anquilose/diagnóstico por imagem , Adulto , Seguimentos , Espondiloartrite Axial/etiologia , Espondiloartrite Axial/diagnóstico , Articulação Zigapofisária/diagnóstico por imagem , Articulação Zigapofisária/patologia , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/complicações , RadiografiaRESUMO
Both nanopore-based DNA sequencing and CRISPR/Cas-based gene editing represent groundbreaking innovations in molecular biology and genomics, offering unprecedented insights into and tools for working with genetic information. For students, reading, editing, and even writing DNA will be part of their everyday life. We have developed a laboratory procedure that includes (i) the biosynthesis of a guide RNA for, (ii) targeting Cas9 to specifically linearize the pBR322 plasmid, and (iii) the identification of the cutting site through nanopore DNA sequencing. The protocol is intentionally kept simple and requires neither living organisms nor biosafety laboratories. We divided the experimental procedures into separate activities to facilitate customization. Assuming access to a well-equipped molecular biology laboratory, an initial investment of approximately $2,700 is necessary. The material costs for each experiment group amount to around $130. Furthermore, we have developed a freely accessible website (https://dnalesen.hs-mittweida.de) for sequence read analysis and visualization, lowering the required computational skills to a minimum. For those with strong computational skills, we provide instructions for terminal-based data processing. With the presented activities, we aim to provide a hands-on experiment that engages students in modern molecular genetics and motivates them to discuss potential implications. The complete experiment can be accomplished within half a day and has been successfully implemented by us at high schools, in teacher training, and at universities. Our tip is to combine CRISPR/Cas gene targeting with nanopore-based DNA sequencing. As a tool, we provide a website that facilitates sequence data analysis and visualization.
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Prostate cancer (PCa) is a significant health problem in the male population of the Western world. Magnetic resonance elastography (MRE), an emerging medical imaging technique sensitive to mechanical properties of biological tissues, detects PCa based on abnormally high stiffness and viscosity values. Yet, the origin of these changes in tissue properties and how they correlate with histopathological markers and tumor aggressiveness are largely unknown, hindering the use of tumor biomechanical properties for establishing a noninvasive PCa staging system. To infer the contributions of extracellular matrix (ECM) components and cell motility, we investigated fresh tissue specimens from two PCa xenograft mouse models, PC3 and LNCaP, using magnetic resonance elastography (MRE), diffusion-weighted imaging (DWI), quantitative histology, and nuclear shape analysis. Increased tumor stiffness and impaired water diffusion were observed to be associated with collagen and elastin accumulation and decreased cell motility. Overall, LNCaP, while more representative of clinical PCa than PC3, accumulated fewer ECM components, induced less restriction of water diffusion, and exhibited increased cell motility, resulting in overall softer and less viscous properties. Taken together, our results suggest that prostate tumor stiffness increases with ECM accumulation and cell adhesion - characteristics that influence critical biological processes of cancer development. MRE paired with DWI provides a powerful set of imaging markers that can potentially predict prostate tumor development from benign masses to aggressive malignancies in patients. STATEMENT OF SIGNIFICANCE: Xenograft models of human prostate tumor cell lines, allowing correlation of microstructure-sensitive biophysical imaging parameters with quantitative histological methods, can be investigated to identify hallmarks of cancer.
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Movimento Celular , Técnicas de Imagem por Elasticidade , Matriz Extracelular , Neoplasias da Próstata , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/diagnóstico por imagem , Humanos , Matriz Extracelular/patologia , Matriz Extracelular/metabolismo , Técnicas de Imagem por Elasticidade/métodos , Animais , Camundongos , Linhagem Celular Tumoral , Imagem de Difusão por Ressonância Magnética/métodosRESUMO
Magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI) are complementary imaging techniques that detect disease based on viscoelasticity and water mobility, respectively. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering the clinical translation of combined DWI-MRE markers. We used DWI-MRE to study 129 biomaterial samples including native and cross-linked collagen, glycosaminoglycans (GAGs) with different sulfation levels, and decellularized specimens of pancreas and liver, all with different proportions of solid tissue, or solid fractions. We developed a theoretical framework of the relationship between mechanical loss and tissue-water mobility based on two parameters, solid and fluid viscosity. These parameters revealed distinct DWI-MRE property clusters characterizing weak, moderate, and strong water-network interactions. Sparse networks interacting weakly with water, such as collagen or diluted decellularized tissue, resulted in marginal changes in water diffusion over increasing solid viscosity. In contrast, dense networks with larger solid fractions exhibited both free and hindered water diffusion depending on the polarity of the solid components. For example, polar and highly sulfated GAGs as well as native soft tissues hindered water diffusion despite relatively low solid viscosity. Our results suggest that two fundamental properties of tissue networks, solid fraction and network polarity, critically influence solid and fluid viscosity in biological tissues. Since clinical DWI and MRE are sensitive to these viscosity parameters, the framework we present here can be used to detect tissue remodeling and architectural changes in the setting of diagnostic imaging. STATEMENT OF SIGNIFICANCE: The viscoelastic properties of biological tissues provide a wealth of information on the vital state of cells and host matrix. Combined measurement of viscoelasticity and water diffusion by medical imaging is sensitive to tissue microarchitecture. However, the relationship between viscoelasticity and water diffusion is still poorly understood, hindering full exploitation of these properties as a combined clinical biomarker. Therefore, we analyzed the parameter space accessible by diffusion-weighted imaging (DWI) and magnetic resonance elastography (MRE) and developed a theoretical framework for the relationship between water mobility and mechanical parameters in biomaterials. Our theory of solid material properties related to particle motion can be translated to clinical radiology using clinically established MRE and DWI.
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Elasticidade , Água , Viscosidade , Água/química , Difusão , Animais , Técnicas de Imagem por Elasticidade/métodos , Humanos , Imagem de Difusão por Ressonância Magnética/métodos , Colágeno/química , Glicosaminoglicanos/metabolismo , Glicosaminoglicanos/química , Fígado/diagnóstico por imagemRESUMO
OBJECTIVES: Radiography and MRI of the sacroiliac joints (SIJ) are relevant for the diagnosis and classification of patients with axial spondyloarthritis (axSpA). This study aimed to evaluate the impact of clinical information (CI) on the accuracy of imaging interpretation. METHODS: Out of 109 patients referred because of suspicion of axSpA with complete imaging sets (radiographs and MRI of SIJ), 61 were diagnosed with axSpA (56%). Images were independently evaluated by three radiologists in four consecutive reading campaigns: radiographs and radiographs+MRI without and with CI including demographic data, SpA features, physical activity and pregnancy. Radiographs were scored according to the modified New York criteria, and MRIs for inflammatory and structural changes compatible with axSpA (yes/no). The clinical diagnosis was taken as reference standard. The compatibility of imaging findings with a diagnosis of axSpA (precision) before and after the provision of CI and radiologists' confidence with their findings (0-10) were evaluated. RESULTS: The precision of radiographs evaluation without versus with CI increased from 70% to 78% (p=0.008), and for radiographs+MRI from 81% to 82% (p=1.0), respectively. For CR alone, the sensitivity and specificity of radiologic findings were 51% and 94% without and 60% and 100% with CI, while, for radiographs+MRI, they were 74% and 90% vs 71% and 98%, respectively. The diagnostic confidence of radiologists increased from 5.2±1.9 to 6.0±1.7 with CI for radiographs, and from 6.7±1.6 to 7.2±1.6 for radiographs+MRI, respectively. CONCLUSION: The precision, specificity and diagnostic confidence of radiologic evaluation increased when CI was provided.
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Espondiloartrite Axial , Espondilartrite , Espondilite Anquilosante , Humanos , Articulação Sacroilíaca/diagnóstico por imagem , Espondilartrite/diagnóstico por imagem , Radiografia , Espondilite Anquilosante/diagnósticoRESUMO
Axial spondyloarthritis (axSpA) is an inflammatory rheumatic disease typically characterized by inflammatory back pain (IBP). The term axSpA has largely replaced the long-used term ankylosing spondylitis (AS). IBP is caused by inflammation in the axial skeleton, with the sacroiliac joints (SIJ) being particularly frequently affected initially. The spine is usually added in later stages, which is then increasingly characterized structurally by the formation of new bone. The overall concept of spondyloarthritis includes other disease manifestations such as uveitis, psoriasis and colitis and comorbidities such as cardiovascular disease and osteoporosis.The ASAS classification criteria for axSpA, in place since 2009, have replaced the 1984 modified New York criteria. In the former, in addition to conventional X-rays, changes in the SIJ detected by magnetic resonance imaging (MRI) and also the detection of HLA B27 have, for the first time, played a role. It is important to note that these are not diagnostic criteria, as they do not exist. This paper outlines 10 points that should be considered when making a diagnosis.
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Espondilartrite , Espondilite Anquilosante , Humanos , Espondilartrite/diagnóstico por imagem , Espondilite Anquilosante/diagnóstico por imagem , Articulação Sacroilíaca/diagnóstico por imagem , Radiografia , Coluna Vertebral , Imageamento por Ressonância Magnética/métodosRESUMO
Time-harmonic elastography (THE) is an emerging ultrasound imaging technique that allows full-field mapping of the stiffness of deep biological tissues. THE's unique ability to rapidly capture stiffness in multiple tissues has never been applied for imaging skeletal muscle. Therefore, we addressed the lack of data on temporal changes in skeletal muscle stiffness while simultaneously covering stiffness of different muscles. Acquiring repeated THE scans every five seconds we quantified shear-wave speed (SWS) as a marker of stiffness of the long head (LHB) and short head (SHB) of biceps brachii and of the brachialis muscle (B) in ten healthy volunteers. SWS was continuously acquired during a 3-min isometric preloading phase, a 3-min loading phase with different weights (4, 8, and 12 kg), and a 9-min postloading phase. In addition, we analyzed temporal SWS standard deviation (SD) as a marker of muscle contraction regulation. Our results (median [min, max]) showed both SWS at preloading (LHB: 1.04 [0.94, 1.12] m/s, SHB: 0.86 [0.78, 0.94] m/s, B: 0.96 [0.87, 1.09] m/s, pâ¯<â¯0.001) and the increase in SWS with loading weight to be muscle-specific (LHB: 0.010 [0.002, 0.019] m/s/kg, SHB: 0.022 [0.017, 0.042] m/s/kg, B: 0.039 [0.019, 0.062] m/s/kg, pâ¯<â¯0.001). Additionally, SWS during loading increased continuously over time by 0.022 [0.004, 0.051] m/s/min (pâ¯<â¯0.01). Using an exponential decay model, we found an average relaxation time of 27 seconds during postloading. Analogously, SWS SD at preloading was also muscle-specific (LHB: 0.018 [0.011, 0.029] m/s, SHB: 0.021 [0.015, 0.027] m/s, B: 0.024 [0.018, 0.037] m/s, pâ¯<â¯0.05) and increased by 0.005 [0.003, 0.008] m/s/kg (pâ¯<â¯0.01) with loading. SWS SD did not change over loading time and decreased immediately in the postloading phase. Taken together, THE of skeletal muscle is a promising imaging technique for in vivo quantification of stiffness and stiffness changes in multiple muscle groups within seconds. Both the magnitude of stiffness changes and their temporal variation during isometric exercise may reflect the functional status of skeletal muscle and provide additional information to the morphological measures obtained by conventional imaging modalities.
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BACKGROUND: Individuals with anti-citrullinated protein antibodies (ACPAs) and subclinical inflammatory changes in joints are at high risk of developing rheumatoid arthritis. Treatment strategies to intercept this pre-stage clinical disease remain to be developed. We aimed to assess whether 6-month treatment with abatacept improves inflammation in preclinical rheumatoid arthritis. METHODS: The abatacept reversing subclinical inflammation as measured by MRI in ACPA positive arthralgia (ARIAA) study is a randomised, international, multicentre, double-blind, placebo-controlled trial done in 14 hospitals and community centres across Europe (11 in Germany, two in Spain, and one in the Czech Republic). Adults (aged ≥18 years) with ACPA positivity, joint pain (but no swelling), and signs of osteitis, synovitis, or tenosynovitis in hand MRI were randomly assigned (1:1) to weekly subcutaneous abatacept 125 mg or placebo for 6 months followed by a double-blind, drug-free, observation phase for 12 months. The primary outcome was the proportion of participants with any reduction in inflammatory MRI lesions at 6 months. The primary efficacy analysis was done in the modified intention-to-treat population, which included participants who were randomly assigned and received study medication. Safety analyses were conducted in participants who received the study medication and had at least one post-baseline observation. The study was registered with the EUDRA-CT (2014-000555-93). FINDINGS: Between Nov 6, 2014, and June 15, 2021, 139 participants were screened. Of 100 participants, 50 were randomly assigned to abatacept 125 mg and 50 to placebo. Two participants (one from each group) were excluded due to administration failure or refusing treatment; thus, 98 were included in the modified intention-to-treat population. 70 (71%) of 98 participants were female and 28 (29%) of 98 were male. At 6 months, 28 (57%) of 49 participants in the abatacept group and 15 (31%) of 49 participants in the placebo group showed improvement in MRI subclinical inflammation (absolute difference 26·5%, 95% CI 5·9-45·6; p=0·014). Four (8%) of 49 participants in the abatacept group and 17 (35%) of 49 participants in the placebo group developed rheumatoid arthritis (hazard ratio [HR] 0·14 [0·04-0·47]; p=0·0016). Improvement of MRI inflammation (25 [51%] of 49 participants in the abatacept group, 12 [24%] of 49 in the placebo group; p=0·012) and progression to rheumatoid arthritis (17 [35%] of 49, 28 [57%] of 49; HR 0·14 [0·04-0·47]; p=0·018) remained significantly different between the two groups after 18 months, 12 months after the end of the intervention. There were 12 serious adverse events in 11 participants (four [8%] of 48 in the abatacept group and 7 [14%] of 49 in the placebo group). No deaths occurred during the study. INTERPRETATION: 6-month treatment with abatacept decreases MRI inflammation, clinical symptoms, and risk of rheumatoid arthritis development in participants at high risk. The effects of the intervention persist through a 1-year drug-free observation phase. FUNDING: Innovative Medicine Initiative.
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Antirreumáticos , Artrite Reumatoide , Adulto , Masculino , Humanos , Feminino , Adolescente , Abatacepte/efeitos adversos , Antirreumáticos/efeitos adversos , Resultado do Tratamento , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Inflamação/tratamento farmacológico , Artralgia/induzido quimicamenteRESUMO
AIM: For diseases caused by calcium pyrophosphate deposition (CPPD), validated classification criteria were previously lacking. In this article the recently developed and validated classification criteria are translated, explained, and assessed. METHODS: In recent years a multinational research group developed classification criteria for CPPD disease with the support by the European Alliance of Associations for Rheumatology (EULAR) and the American College of Rheumatology (ACR), following an established method. The developed criteria were finally validated in an independent cohort. The translation and annotation of the new first classification criteria were carried out in an iterative procedure in consensus with the authors. RESULTS: The presence of a crowned dens syndrome or calcium pyrophosphate crystals in the synovial fluid in patients with pain, swelling or sensitivity of the joints (entry criterion) is sufficient for the classification as CPPD disease, where the symptoms cannot be completely explained by another rheumatic disease (exclusion criterion). If these symptoms are not present, a count of more than 56 points based on weighted criteria comprised of clinical features and the results of laboratory and imaging investigations can be included for classification as a CPPD disease. These criteria had a sensitivity of 92.2% and a specificity of 87.9% in the derivation cohorts (190 CPPD cases and 148 mimics), whereas the sensitivity was 99.2% and the specificity 92.5% in the validation cohorts (251 CPPD cases and 162 mimics). CONCLUSION: The ACR/EULAR classification criteria 2023 of a CPPD disease will facilitate clinical research in this field. The use in the clinical routine will show how practical the criteria are.
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Condrocalcinose , Sensibilidade e Especificidade , Condrocalcinose/classificação , Condrocalcinose/diagnóstico , Humanos , Alemanha , Reprodutibilidade dos Testes , Tradução , Reumatologia/normas , Pirofosfato de Cálcio/metabolismo , Terminologia como Assunto , Diagnóstico DiferencialRESUMO
OBJECTIVE: To compare the response to nonsteroidal antiinflammatory drugs (NSAIDs) in patients with longstanding axial spondyloarthritis (axSpA) and controls with back pain (nonspondyloarthritis [non-SpA]). METHODS: Consecutive outpatients with chronic back pain (axSpA or non-SpA), were prospectively recruited. Any previous NSAIDs were withdrawn 2 days before study start (baseline). Back pain was assessed using a numerical rating scale (NRS; range 0-10) starting at 2 hours after baseline and several times thereafter up to 4 weeks. "Any response" to NSAIDs was defined as improvement of back pain on the NRS > 2 units, and "good response" as improvement > 50%, compared to baseline. RESULTS: Among 233 patients included, 68 had axSpA (29.2%) and 165 had non-SpA back pain (70.8%). The mean age was 42.7 (SD 10.7) vs 49.3 (SD 11.1) years, symptom duration 15.1 (SD 11.1) years vs 14.6 (SD 11.9) years, and pain score 5.9 (SD 2.3) vs 6.3 (SD 2.0), respectively. Overall, of patients with axSpA or non-SpA back pain, 30.9% vs 29.1% of patients showed any response and 23.5% vs 16.4% of patients showed a good response after 4 weeks, respectively (P value not significant). No differences were found in the rapidity of response or between subgroups of patients based on demographics, including different stages of axSpA. CONCLUSION: No major differences in the response to NSAIDs were found between patients with axSpA and those with non-SpA with longstanding chronic back pain. The item in the Assessment of SpondyloArthritis international Society classification criteria on "response to NSAIDs" needs more study.
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Espondiloartrite Axial , Espondilartrite , Humanos , Adulto , Pacientes Ambulatoriais , Dor nas Costas/diagnóstico , Dor nas Costas/tratamento farmacológico , Espondilartrite/complicações , Espondilartrite/diagnóstico , Espondilartrite/tratamento farmacológico , Anti-Inflamatórios não Esteroides/uso terapêuticoRESUMO
Multiple sclerosis (MS) is a chronic neuroinflammatory disease that involves both white and gray matter. Although gray matter damage is a major contributor to disability in MS patients, conventional clinical magnetic resonance imaging (MRI) fails to accurately detect gray matter pathology and establish a clear correlation with clinical symptoms. Using magnetic resonance elastography (MRE), we previously reported global brain softening in MS and experimental autoimmune encephalomyelitis (EAE). However, it needs to be established if changes of the spatiotemporal patterns of brain tissue mechanics constitute a marker of neuroinflammation. Here, we use advanced multifrequency MRE with tomoelastography postprocessing to investigate longitudinal and regional inflammation-induced tissue changes in EAE and in a small group of MS patients. Surprisingly, we found reversible softening in synchrony with the EAE disease course predominantly in the cortex of the mouse brain. This cortical softening was associated neither with a shift of tissue water compartments as quantified by T2-mapping and diffusion-weighted MRI, nor with leukocyte infiltration as seen by histopathology. Instead, cortical softening correlated with transient structural remodeling of perineuronal nets (PNNs), which involved abnormal chondroitin sulfate expression and microgliosis. These mechanisms also appear to be critical in humans with MS, where tomoelastography for the first time demonstrated marked cortical softening. Taken together, our study shows that neuroinflammation (i) critically affects the integrity of PNNs in cortical brain tissue, in a reversible process that correlates with disease disability in EAE, (ii) reduces the mechanical integrity of brain tissue rather than leading to water accumulation, and (iii) shows similar spatial patterns in humans and mice. These results raise the prospect of leveraging MRE and quantitative MRI for MS staging and monitoring treatment in affected patients.
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Técnicas de Imagem por Elasticidade , Encefalomielite Autoimune Experimental , Esclerose Múltipla , Humanos , Animais , Camundongos , Doenças Neuroinflamatórias , Imageamento por Ressonância Magnética , Imagem de Difusão por Ressonância Magnética , Encefalomielite Autoimune Experimental/diagnóstico por imagem , ÁguaRESUMO
OBJECTIVES: To determine if there were differences in the Assessment of SpondyloArthritis international Society Health Index (ASAS HI) scores between patients classified as radiographic axial spondyloarthritis (r-axSpA) and non-radiographic axSpA (nr-axSpA), and to identify factors associated with higher ASAS HI scores in both disease phenotypes. METHODS: This study was an ancillary analysis of the ASAS HI international validation project performed in 23 countries. Patients were included if they were ≥18 years of age and diagnosed with axSpA. Univariable and multivariable analysis were performed to determine if ASAS HI scores differed between the axSpA phenotypes, and to identify other variables associated with ASAS HI scores. We also tested for potential interactions between the axSpA phenotype and significant variables identified through the multivariable regression. RESULTS: A total of 976 patients were included, with 703 having r-axSpA and 273 nr-axSpA. Patients with r-axSpA reported higher (worse) ASAS HI scores compared with those with nr-axSpA (6.8 (4.4) vs 6.0 (4.0), p=0.02), but the axSpA phenotype was not associated with ASAS HI scores in the multivariable regression (ß: -0.19, 95% CI: -0.56 to 0.19). Female gender, having worse physical function (Bath Ankylosing Spondylitis Functional Index), disease activity (Ankylosing Spondylitis Disease Activity Score) and anxiety and depressive symptoms (Hospital Anxiety and Depression Scale) were associated with higher ASAS HI scores. No interactions were found to be significant. CONCLUSION: Overall health and functioning are similarly affected in patients with r-axSpA and nr-axSpA. Female patients, having worse physical function, disease activity, anxiety and depressive symptoms were independently associated with higher ASAS HI scores.
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Espondiloartrite Axial não Radiográfica , Espondilartrite , Espondilite Anquilosante , Humanos , Feminino , Espondilite Anquilosante/diagnóstico , Espondilartrite/diagnóstico , Espondilartrite/epidemiologia , Ansiedade , FenótipoRESUMO
OBJECTIVE: Patients with axial spondyloarthritis (axSpA) suffer from clinical symptoms like morning stiffness and back pain. Mobility of patients with axSpA is often impaired. The aim of this study is to compare the performance of patients with axSpA regarding mobility measures including performance-based tests and objective electronic assessments with the Epionics SPINE device (ES) at different times of the day compared with healthy controls (HC). METHODS: Observational trial, consecutive inpatients with axSpA (n=100) and 20 HCs were examined in the morning (V1: before 10:00 am) and in the afternoon (V2: after 02:00 pm) by the Bath Ankylosing Spondylitis Metrology Index (BASMI), the AS physical performance index (ASPI), the Short Physical Performance Battery (SPPB) and ES measurements, including range of motion (RoM) and range of kinematics (RoK). RESULTS: The assessments of patients with axSpA performed in the morning clearly differed from those in the afternoon, especially regarding performance-based tests. Significant improvements were seen for BASMI (4.0±3.8 to 3.8±1.9; p<0.001), ASPI (36.2±18.3 to 28.8±11.9 s; p<0.001), SPPB (10.1±1.5 to 10.7±1.4 points; p<0.001) and for ES measures of speed (RoK; p<0.018) but not for RoM, except for lateral flexion (13.3±7.4 to 14.7±8.2°; p=0.002). This time of assessment-related variability was not observed in HC. CONCLUSION: The spinal mobility of patients with axSpA was worse in the morning but significantly improved in the afternoon. This was captured best by performance-based measures and was not seen in HC. The diurnal variation of mobility has implications for clinical studies, suggesting that the time of assessments needs to be standardised.
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Espondiloartrite Axial , Espondilite Anquilosante , Humanos , Coluna Vertebral , Pacientes Internados , Espondilite Anquilosante/complicações , Espondilite Anquilosante/diagnósticoRESUMO
Ankylosing spondylitis (AS) is the historic term used for decades for the HLA-B27-associated inflammatory disease affecting mainly the sacroiliac joints (SIJ) and spine. Classification criteria for AS have radiographic sacroiliitis as a dominant characteristic. However, with the availability of MRI of SIJ, it could be demonstrated that the disease starts long before definite SIJ changes become visible on radiographs. The Assessment of SpondyloArthritis international Society, representing a worldwide group of experts reached consensus on changes in the nomenclature pertaining to axial spondyloarthritis (axSpA), such as the terminology of diagnosis and of assessment of disease activity tools. These are important changes in the field, as experts in axSpA are now in agreement that the term axSpA is the overall term for the disease. A further differentiation, of which radiographic versus non-radiographic is only one aspect, may be relevant for research purposes. Another important decision was that the terms AS and radiographic axSpA (r-axSpA) can be used interchangeably, but that the preferred term is r-axSpA. Based on the decision that axSpA is the correct terminology, a proposal was made to officially change the meaning of the ASDAS acronym to 'Axial Spondyloarthritis Disease Activity Score'. In addition, for simplification it was proposed that the term ASDAS (instead of ASDAS-CRP) should be preferred and applied to the ASDAS calculated with C reactive protein (CRP). It is hoped that these changes will be used consequently for education, in textbooks, manuscripts and presentations.
Assuntos
Sacroileíte , Espondilartrite , Espondilite Anquilosante , Humanos , Espondilite Anquilosante/diagnóstico , Índice de Gravidade de Doença , Espondilartrite/diagnóstico , Articulação Sacroilíaca/diagnóstico por imagem , Sacroileíte/diagnóstico por imagem , Proteína C-ReativaRESUMO
BACKGROUND: The association of the human lymphocyte antigen B27 (HLA-B27) with ankylosing spondylitis (AS), also now called axial spondylarthritis (axSpA), was first described 50 years ago. OBJECTIVE: This article gives an overview of the available knowledge on the topic. MATERIAL AND METHODS: This is a narrative review based on the experience of the authors. RESULTS: The HLA-B27 is a member of the HLA class I family of genes of the major histocompatibility complex (MHC). The prevalence of HLA-B27 in the central European population is approximately 8â¯%, i.e., the vast majority of carriers of HLA-B27+ remain healthy. The frequency of HLA-B27 shows a decline from north to south. The HLA-B27 explains only 30â¯% of the genetic burden of axSpA. The prevalence of the disease correlates with the frequency of HLA-B27 in the population, i.e., there are geographic differences. Approximately 60-90â¯% of patients with axSpA worldwide are HLA-B27+. Some 200 subtypes of HLA-B27 can be differentiated using the polymerase chain reaction (PCR). In Thailand and Sardinia two subtypes were found that are not associated with axSpA. The physiological function of HLA class I molecules is the defence of the organism against microbes. Microbial peptides are presented to the immune system, which can be specifically attacked by CD8+ Tcells. Genetic polymorphisms of the enzyme endoplasmic reticulum aminopeptidase 1 (ERAP1), which breaks down peptides in the endoplasmic reticulum, are associated only with HLA-B27+ diseases. DISCUSSION: The pathogenesis of axSpA is unclear but a major hypothesis is that of the arthritogenic peptides. In this it is assumed that potentially pathogenic foreign or autologous peptides can be presented by HLA-B27. If nothing else, HLA-B27 plays an important role in the diagnosis, classification and determination of the severity of axSpA.
Assuntos
Espondilartrite , Espondilite Anquilosante , Humanos , Antígeno HLA-B27/genética , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/genética , Peptídeos/genética , Polimorfismo Genético , Espondilartrite/diagnóstico , Espondilartrite/genética , Aminopeptidases/genética , Antígenos de Histocompatibilidade MenorRESUMO
OBJECTIVE: The objective of this study is to build a structural model visualising and quantifying the interrelationships of different disease outcomes with the Assessment of SpondyloArthritis International Society Health Index (ASAS HI) in patients with axial spondyloarthritis (axSpA). METHODS: Cross-sectional data collected at month 72 of the Devenir des Spondylarthropathies Indifferénciées Récentes cohort was analysed. Combining prior knowledge and observed data, probabilistic Bayesian network modelling was used to study how the interplay of different disease outcomes affects the ASAS HI, which measures disease-specific overall functioning and health. Disease outcomes comprised, among others, the Ankylosing Spondylitis (AS) Disease Activity Score (ASDAS) and the Bath AS Functional Index (BASFI). RESULTS: Data of 384 patients were analysed. The obtained structure suggests that ASAS HI is determined by both patient-reported physical function (BASFI) and disease activity (ASDAS). The parameters of the structural model show that an increase of ASDAS or BASFI by 1 unit corresponds to an increase of ASAS HI by 0.70 or 1.25 units, respectively. Moreover, the model suggests that disease activity has an indirect impact on ASAS HI via BASFI. No relationship between spinal mobility or structural damage and ASAS HI was found. CONCLUSIONS: This is the first structural model developed to better understand the construct and the interplay between clinically relevant outcomes related to ASAS HI in axSpA patients. It shows that disease activity and physical function have a strong impact on ASAS HI, confirming it to be a valid construct of overall functioning and health in axSpA patients.