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Frontiers in Immunology 2024levels are elevated in the blood and synovial fluid of patients with inflammatory arthritis. can be produced by Th17 cells and locally within joints by tissue-resident...
OBJECTIVES
levels are elevated in the blood and synovial fluid of patients with inflammatory arthritis. can be produced by Th17 cells and locally within joints by tissue-resident cells. induces osteoblast mineralization . As osteoproliferation and Th17 cells are important factors in the pathogenesis of axial spondyloarthritis (axSpA), we aimed to clarify the cellular sources of in spondyloarthritis.
METHODS
Serum, peripheral blood mononuclear cells ( = 15-35) and synovial tissue ( = 3-9) of adult patients with axSpA, psoriatic arthritis (PsA) and rheumatoid arthritis (RA) and healthy controls (HCs, = 5) were evaluated by ELISA, flow cytometry including PrimeFlow assay, immunohistochemistry and immunofluorescence and quantitative PCR.
RESULTS
Synovial tissue of axSpA patients shows significantly more -positive cells than that of HCs ( < 0.01), but numbers are also elevated in PsA and RA patients. Immunofluorescence shows co-localization of with CD68, but not with CD3, SMA, CD163, cadherin-11, or CD90. is elevated in the serum of RA and PsA (but not axSpA) patients compared with HCs ( < 0.001 and < 0.01). However, peripheral blood CD4 T cells from axSpA and PsA patients show higher positivity for in the PrimeFlow assay compared with HCs. CD4 memory T cells from axSpA patients produce more under Th17-favoring conditions (IL-1β and IL-23) than cells from PsA and RA patients or HCs.
CONCLUSION
production is increased in the synovial tissue of SpA and can be localized to CD68 macrophage-like synoviocytes, whereas circulating Th17 cells are only modestly enriched. Considering the osteoproliferative properties of , this offers new therapeutic options independent of Th17 pathways.
Topics: Humans; Arthritis, Psoriatic; Synoviocytes; Male; Adult; Female; Antigens, CD; Interleukins; Middle Aged; Antigens, Differentiation, Myelomonocytic; Axial Spondyloarthritis; Th17 Cells; Synovial Membrane; Joints; Arthritis, Rheumatoid
PubMed: 38799447
DOI: 10.3389/fimmu.2024.1355824 -
Arthritis Research & Therapy May 2024Tofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Time to improvement in core domains of AS was estimated in... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Tofacitinib is an oral Janus kinase inhibitor for treatment of ankylosing spondylitis (AS). Time to improvement in core domains of AS was estimated in tofacitinib-treated patients with AS.
METHODS
This post hoc analysis used phase 3 trial data from patients with AS receiving tofacitinib 5 mg twice daily or placebo to week (W)16; all patients received open-label tofacitinib W16-48.
OUTCOMES
nocturnal pain; total back pain; fatigue, spinal pain, peripheral joint pain/swelling, enthesitis, and morning stiffness (Bath AS Disease Activity Index [BASDAI] questions 1-6); BASDAI total score; AS Disease Activity Score (ASDAS). Median time to improvement events was estimated using non-parametric Kaplan-Meier models. Improvement events were defined as initial (first post-baseline observation) and continued (sustained for 2 consecutive visits) ≥ 30% and ≥ 50% improvement in back/nocturnal pain or BASDAI questions/total scores, or ASDAS improvement ≥ 1.1 and ≥ 2.0 points.
RESULTS
269 patients (tofacitinib: n = 133; placebo-to-tofacitinib: n = 136) were assessed. Median time to improvement was shorter, and more patients experienced improvements with tofacitinib vs. placebo-to-tofacitinib; differences observed from W2 (first post-baseline assessment). Median time to initial (continued) ≥ 30% pain improvement was 4 (4-8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib (8 [8] weeks post-switch). Median time to initial (continued) ≥ 50% improvement of pain, peripheral joint pain/swelling and enthesitis, morning stiffness, BASDAI total score, and fatigue was 8-24 (12-40) weeks with tofacitinib vs. 24-32 weeks (32 weeks-not estimable [NE]) with placebo-to-tofacitinib. Median time to initial (continued) ASDAS improvement ≥ 1.1 points was 4 (8) weeks for tofacitinib vs. 24 (24) weeks for placebo-to-tofacitinib, and NE for improvement ≥ 2.0 points with either treatment.
CONCLUSIONS
Improvements in AS core domains occurred more rapidly with tofacitinib vs. placebo-to-tofacitinib. Half of tofacitinib-treated patients with AS will likely experience improvements ≥ 30% in pain and ≥ 1.1 points in ASDAS during month (M)1, ≥ 50% improvement in nocturnal pain and enthesitis by M2, and in morning stiffness by M3. Results show that initiating tofacitinib as soon as possible is associated with quicker improvements in AS core domains vs. delaying treatment.
TRIAL REGISTRATION
ClinicalTrials.gov, NCT03502616, 11 April 2018.
Topics: Humans; Piperidines; Spondylitis, Ankylosing; Pyrimidines; Female; Male; Adult; Pyrroles; Middle Aged; Treatment Outcome; Fatigue; Double-Blind Method; Pain; Time Factors; Protein Kinase Inhibitors
PubMed: 38790040
DOI: 10.1186/s13075-024-03313-w -
Journal of Orthopaedic Case Reports May 2024Ankylosing spinal disorders present significant challenges in cases of trauma, and the treatment of ankylosed spine infections may also be challenging. However, to the...
INTRODUCTION
Ankylosing spinal disorders present significant challenges in cases of trauma, and the treatment of ankylosed spine infections may also be challenging. However, to the best of our knowledge, only one study to date has addressed this topic, reporting a mortality rate of 62%.
CASE REPORT
Our patients were four men and one woman with a mean age of 72 years. Treatments consisted of intravenous antibiotics, a hard brace, and surgical interventions including percutaneous pedicle screw fixation in two patients, laminectomy and evacuation of the epidural abscess in one, and percutaneous lavage of the affected disc in two. The time from referral to intervention averaged 16 days. The mortality rate was 0% with healing of the infection with segmental bony fusion in four patients.
CONCLUSION
This is the second reported case series of ankylosed spine infections. Early surgical intervention aimed at drainage or stabilization of the infectious lesions is crucial to disease control.
PubMed: 38784890
DOI: 10.13107/jocr.2024.v14.i05.4436 -
Journal of Orthopaedic Case Reports May 2024Coalition is an abnormal, usually congenital, or developmental connection in between or the complete fusion of two bones that are otherwise separate. It is of three...
INTRODUCTION
Coalition is an abnormal, usually congenital, or developmental connection in between or the complete fusion of two bones that are otherwise separate. It is of three types, i.e., synostosis (bony connection), synchondrosis (cartilaginous connection), or syndesmosis (fibrous tissue). Its typical cause is the failure of mesenchymal segmentation and differentiation. Usually, it is seen in tarsal or carpal bones and very rarely in between other bones. Only a single case of a tibiotalar coalition has been reported previously in literature. Herein, we are reporting a case of the talocrural coalition, which is the first one from the Indian sub-continent.
CASE REPORT
A 16-year-old moderately built female patient of Indian origin presented with chronic pain of 1-year duration in the right foot and ankle region on weight bearing. The pain was dull aching type, mild-to-moderate in severity and worsened with activity or prolonged walking, and relieved on taking non-steroidal anti-inflammatory drugs. No relevant history was present. On local examination, diffuse tenderness was present in the ankle and the tarsal bones. Almost negligible dorsiflexion and about 15° plantar flexion of the foot were possible. An initial radiograph of the right ankle revealed osseous fusion between the distal tibia and fibula, as well as between the tibia, fibula, and the dome of the talus. Magnetic resonance imaging (MRI) revealed osseous fusion involving the distal tibia, fibula, and the dome of the talus (both medially and laterally), indicative of talocrural fusion. No edema or inflammation was appreciable in the adjacent tendons or synovium. The patient was explained regarding the pathology and the prognosis. She was managed conservatively and was satisfied.
CONCLUSION
Radiographs play a crucial role in evaluating patients suspected of having a coalition or ankylosis. Complementary tools such as computed tomography and MRI are valuable for a more in-depth assessment of the fusion and aid in surgical planning.
PubMed: 38784884
DOI: 10.13107/jocr.2024.v14.i05.4424 -
JPMA. the Journal of the Pakistan... May 2024To measure the levels of superoxide dismutase and malondialdehyde along with erythrocyte sedimentation rate and C-reactive protein in patients of rheumatoid arthritis... (Comparative Study)
Comparative Study
OBJECTIVES
To measure the levels of superoxide dismutase and malondialdehyde along with erythrocyte sedimentation rate and C-reactive protein in patients of rheumatoid arthritis and ankylosing spondylitis.
METHODS
The comparative, cross-sectional study was conducted from February 2 to December 30, 2022, at the Centre for Research in Experimental and Applied Medicine laboratory of the Department of Biochemistry and Molecular Biology, Army Medical College, Rawalpindi, Pakistan, in collaboration with the Department of Rheumatology, Pak Emirates Military Hospital, Rawalpindi. The sample comprised healthy controls in group 1, patients of rheumatoid arthritis in group 2 and patients of ankylosing spondylitis in group 3. Blood samples were assessed for levels of superoxide dismutase, malondialdehyde, erythrocyte sedimentation rate and C-reactive protein. Data was analysed using SPSS 25.
RESULTS
Of the 180 subjects, 60(33.3%) were in group 1; 32(53.3%) females and 28(46.7%) males with mean age 34.9±6.4 years. There were 60(33.3%) patients in group 2; 35(58.3%) females and 25(41.7%) males with mean age 46.0±11.1 years. There were 60(33.3%) patients in group 3, and all 60(100%) were males with mean age 35.9±6.9 years. Superoxide dismutase level was significantly low and malondialdehyde level was significantly high in groups 2 and 3 compared to group 1 (p<0.05). Erythrocyte sedimentation rate was the highest in group 2, followed by group 3 (p<0.05). C-reactive protein levels were the highest in group 2 and the lowest in group 3 (p<0.05). A significantly negative correlation (p<0.001) was found between superoxide dismutase and malondialdehyde.
CONCLUSIONS
Oxidative stress played a pivotal role in chronic inflammatory rheumatic diseases, like rheumatoid arthritis and ankylosing spondylitis.
Topics: Humans; Spondylitis, Ankylosing; Male; Female; Arthritis, Rheumatoid; Oxidative Stress; Malondialdehyde; Superoxide Dismutase; Blood Sedimentation; Adult; Cross-Sectional Studies; C-Reactive Protein; Lipid Peroxidation; Middle Aged; Biomarkers; Case-Control Studies; Pakistan
PubMed: 38783435
DOI: 10.47391/JPMA.9286 -
PloS One 2024To evaluate daily physical activity (PA) in relation to psychosocial factors, such as anxiety, depression and different types of coping strategies, as well as patient-...
OBJECTIVE
To evaluate daily physical activity (PA) in relation to psychosocial factors, such as anxiety, depression and different types of coping strategies, as well as patient- and disease-related factors in patients with axial spondyloarthritis (axSpA).
METHODS
Consecutive outpatients from the Groningen Leeuwarden AxSpA (GLAS) cohort completed the modified Short Questionnaire to assess health-enhancing PA (mSQUASH), Hospital Anxiety and Depression Scale (HADS) and Coping with Rheumatic Stressors (CORS) questionnaires, as well as standardized patient- and disease-related assessments. Univariable and multivariable linear regression analyses and comparison of lowest and highest PA tertiles were performed to explore associations between the HADS, CORS, patient- and disease-related factors and PA.
RESULTS
In total, 84 axSpA patients were included; 60% male, mean age 49 (SD ±14) years, median symptom duration 20 (25th-75th percentiles: 12-31) years, mean ASDAS 2.1 (±1.0). Higher PA levels were significantly associated with better scores on patient-reported disease activity (BASDAI), physical function (BASFI) and quality of life (ASQoL). Furthermore, higher levels of PA were associated with less impact of axSpA on wellbeing and lower HADS depression scores. In the multivariable linear regression model, less use of the coping strategy 'decreasing activities' (β: -376.4; p 0.003) and lower BMI (β:-235.5; p: 0.030) were independently associated with higher level of PA. Comparison of patients from the lowest and highest PA tertiles showed results similar to those found in the regression analyses.
CONCLUSION
In this cohort of axSpA patients, higher levels of daily PA were associated with better patient-reported outcomes and lower depression scores. Additionally, the passive coping strategy "decreasing activities" and lifestyle factor BMI were independently associated with PA. Besides anti-inflammatory treatment, coping strategies and lifestyle should be taken into account in the management of individual axSpA patients. Incorporating these aspects into patient education could increase patient awareness and self-efficacy. In the future, longitudinal studies are needed to better understand the complex relationship between patient-, disease- and psychosocial factors associated with daily PA.
Topics: Humans; Male; Female; Quality of Life; Middle Aged; Adaptation, Psychological; Exercise; Adult; Depression; Axial Spondyloarthritis; Surveys and Questionnaires; Anxiety
PubMed: 38758932
DOI: 10.1371/journal.pone.0301965 -
RMD Open May 2024To investigate lectin pathway proteins (LPPs) as biomarkers for axial spondyloarthritis (axSpA) in a cross-sectional cohort with a suspicion of axSpA, comprising newly...
OBJECTIVES
To investigate lectin pathway proteins (LPPs) as biomarkers for axial spondyloarthritis (axSpA) in a cross-sectional cohort with a suspicion of axSpA, comprising newly diagnosed axSpA and chronic low back pain (cLBP) individuals.
METHODS
Serum samples from 515 participants within the OptiRef cohort, including 151 axSpA patients and 364 cLBP patients, were measured using immunoassays for LPPs (mannan-binding lectin (MBL), collectin liver-1 (CL-L1), M-ficolin, H-ficolin and L-ficolin, MBL-associated serine proteases (MASP)-1, -2 and -3, MBL-associated proteins (MAp19 and MAp44) and the complement activation product C3dg).
RESULTS
Serum levels of L-ficolin, MASP-2 and C3dg were elevated in axSpA patients, whereas levels of MASP-3 and CL-L1 were decreased, and this remained significant for C3dg and MASP-3 after adjustment for C reactive protein (CRP). A univariate regression analysis showed serum levels of CL-L1, MASP-2, MASP-3 and C3dg to predict the diagnosis of axSpA, and MASP-3 and C3dg remained significant in a multivariate logistic regression analysis. Assessment of the diagnostic potential showed that a combination of human leukocyte antigen B27 (HLA-B27) and measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, however, with a concomitant loss of sensitivity.
CONCLUSIONS
Serum levels of complement activation, that is, C3dg, and MASP-3 differed significantly between axSpA and cLBP patients after adjustment for CRP. Although combining HLA-B27 with measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, this seems unjustified due to the concomitant loss of sensitivity. However, both C3dg and MASP-3 were associated with axSpA diagnosis in multivariate logistic regression, suggesting an involvement of complement in the inflammatory processes and possibly pathogenesis in axSpA.
Topics: Humans; Biomarkers; Male; Female; Adult; Middle Aged; Cross-Sectional Studies; Complement System Proteins; Axial Spondyloarthritis; Mannose-Binding Protein-Associated Serine Proteases; Lectins; Complement Activation
PubMed: 38749532
DOI: 10.1136/rmdopen-2024-004127 -
Cureus Apr 2024Temporomandibular joint (TMJ) ankylosis is a form of TMJ condition that causes mouth opening limitation, ranging from partial reduction to total immobilization of the...
Temporomandibular joint (TMJ) ankylosis is a form of TMJ condition that causes mouth opening limitation, ranging from partial reduction to total immobilization of the jaw. Bony and fibrous ankylosis is most commonly caused by trauma, although it can also happen as a result of surgery, local or systemic infections, or systemic diseases. Childhood TMJ produces facial deformities, which increase with growth and have a major detrimental impact on the patient's psychological development. Each patient with TMJ ankylosis must have a history, physical examination, and radiographic examination in order to determine a definitive diagnosis, severity, involvement of surrounding tissues, and, ultimately, treatment planning. Technical challenges and a high recurrence rate make treating TMJ ankylosis challenging. Intubating a young child with TMJ ankylosis is a difficult job, which is exacerbated by limited mouth opening. This case report describes a five-year-old boy who reported an inability to open his mouth, diagnosed as TMJ ankylosis, and managed in the absence of an appropriately sized tracheostomy tube.
PubMed: 38741843
DOI: 10.7759/cureus.58153 -
EFORT Open Reviews May 2024Knee stiffness is a widely known and worrying condition in several postoperative knees. Less is known about native stiff knee. The aim of this manuscript is to summarize... (Review)
Review
Knee stiffness is a widely known and worrying condition in several postoperative knees. Less is known about native stiff knee. The aim of this manuscript is to summarize the available literature on native stiff knee epidemiology, classification and treatment. In 1989 stiff knee was defined as a knee with less than 50° of total range of motion. If range of motion is <30°, it is defined as an ankylosed knee. Knee stiffness can be divided into three main types: flexion contractures, extension contractures, and combined contractures. Different risk factors have been associated to native stiff knee and grouped into modifiable or not modifiable. Furthermore, risk factors can be divided into patients' related no patients'-related. Different treatment modalities can be indicated to treat knee stiffness, including manipulation under anesthesia (MUA), arthroscopic and open surgical release. When stiffness is associated with articular disruption TKA represent an option. TKA in native stiff knee can be challenging for the surgeon. Implant's choice and knee exposure are the first steps. In some cases, additional release and extensive can be considered. A stepwise approach and careful preoperative planning are mandatory to obtain long-term satisfactory outcomes. Native stiff knee is a rare but invalidating condition. Different treatment modalities have been proposed as treatment. However, considering that it is frequently associated to sever arthritis, TKA can be an option in painful stiff knees. Nature of knee stiffness necessitates a customized approach to ensure successful management and achieve satisfying outcomes.
PubMed: 38726987
DOI: 10.1530/EOR-24-0034