Endothelial mesenchymal transition promotes pannus formation in ankylosing spondylitis by activation of TGF-ß/SMAD signalling pathway.

OBJECTIVES: To explore the role of endothelial-mesenchymal transition (EndMT) mediated by the TGF-ß/SMAD signalling pathway in the pathogenesis of ankylosing spondylitis (AS). METHODS: Serum levels of TGF-ß1 were measured by enzyme-linked immunosorbent assay (ELISA) in 48 patients with AS and 15 healthy subjects. The expression levels of TGF-ß1, SMAD7, CTGF, CD34 and EndMT-related markers (α-SMA, vimentin, FSP-1, VE-cadherin) in the sacroiliac joint (SIJ) of three AS patients were detected by immunohistochemistry, and three non-spondyloarthritis (SpA) autopsy samples were used as controls. RESULTS: Serum TGF-ß1 level of AS patients was significantly higher than that of healthy controls (22971 ± 7667 pg/ml vs. 14837±4653 pg/ml, p<0.01). Compared with the non-SpA control group, the microvascular density (MVD) at the pannus formation site of SIJ in AS patients was significantly increased, accompanied by respectively increased expressions of TGF-ß1, CTGF, α-SMA, vimentin, and FSP-1 (all p<0.05), whereas respectively decreased expressions of VE-cadherin and SMAD7 (p<0.01). The expression level of FSP-1 was positively correlated with levels of TGF-ß1 and MVD, and negatively correlated with SMAD7. CONCLUSIONS: Our findings show that EndMT is involved in the promotion of pannus formation by TGF-ß/SMAD signalling pathway activation in AS.

Prevalence and risk factors of osteoporosis in patients with ankylosing spondylitis: a 5-year follow-up study of 504 cases.

OBJECTIVES: The objective of this study was to assess the prevalence and risk factors of osteoporosis (OP) in patients with ankylosing spondylitis (AS). METHODS: Demographic and clinical data of 504 AS patients were collected. Bone mineral density (BMD) measurements of the lumbar spine, proximal femur and forearm were performed by dual-energy x-ray absorptiometry at baseline and follow-up. 106 cases of sex- and age-matched healthy volunteers were enrolled as normal controls. RESULTS: In contrast to normal controls, AS patients displayed a higher prevalence of both OP (9.7% vs. 0%) and osteopenia (57.5% vs. 34.9%). The prevalence of OP was significantly higher and the BMD were significantly lower in patients with elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) than patients with normal ESR and CRP. Juvenile onset, morning stiffness lasting over 0.5 hours and elevated ESR levels were risk factors for bone loss at the lumbar spine; Male gender, older age, hip involvement and lack of regular treatment were risk factors for bone loss at the femur. 173 cases were followed up for 1 to 5 years, BMD changes per year at the lumbar spine, femur and forearm were 4.8%, 2.7%, and 2.6% respectively. There was no significant difference in annual BMD change between patients treated with or without low dose glucocorticoids (GCs). Hip involvement and persistent elevated ESR levels, but not GCs treatment, were associated with decreased BMD at both the lumbar spine and the femur during follow-up in longitudinal regression analysis. CONCLUSIONS: High disease activity and hip involvement are risk factors of bone loss in patients with AS. Low-dose GCs treatment in AS does not increase the risk of OP.

Application of OFA-based ERAS for video-assisted thoracoscopic surgery in elderly patients with airway stenosis: A case report.

BACKGROUND: Thoracic surgery without general anesthesia can be traced back to the First World War, and thoracic epidural block was used to complete the operation due to a large number of patients with gunshot wounds who needed emergency thoracic surgery. By reducing the intraoperative opioid dose, intraoperative and postoperative opioid-related adverse events such as respiratory depression, nausea and vomiting, delirium, hyperalgesia, and other side effects can be reduced to the benefit of patients. METHODS: A 72-year-old male patient was admitted to the hospital with a 5-day history of multifocal pain throughout the body caused by a fall. The injury was not treated at that time, and the pain gradually increased, accompanied by cough with difficulty expelling sputum. DIAGNOSES: Left lung contusion; traumatic pneumonia; multiple left rib fractures; left fluid pneumothorax; thyroid tumor of unknown nature, possibly malignant. Grade I tracheal stenosis; Sequelae of cerebral infarction. Because of goiter and severe tracheal compression, the patient was not intubated and received deopiated general anesthesia combined with epidural anesthesia to preserve spontaneous breathing. OUTCOMES: At the end of the video-assisted thoracoscopic exploration, the patient was immediately conscious and returned directly to the ward 6 min later. The patient was able to move freely after surgery and eat normally within 6 h of surgery. The postoperative visual analog scale score was 2 points, and there were no anesthetic complications during the follow-up. CONCLUSION: The opioid-free anesthesia strategy of tubeless general anesthesia, allowing spontaneous breathing combined with epidural anesthesia in elderly patients with tracheal stenosis undergoing video-assisted thoracoscopic surgery can not only avoid accidents and injuries caused by tracheal intubation and mechanical ventilation, but can also significantly reduce postoperative respiratory complications, optimize postoperative analgesia, and help achieve enhanced recovery after surgery.

Tumor Necrosis Factor-Alpha (+489 G/A) Polymorphism Can Predict the Response to Adalimumab in Chinese Han Patients With Ankylosing Spondylitis.

BACKGROUND: Studies investigating the association between single nucleotide polymorphisms (SNPs) of tumor necrosis factor-alpha (TNFα) and the efficacy of adalimumab (ADA) in ankylosing spondylitis (AS) therapy have reported conflicting results. We aimed to investigate the value of SNP typing of TNFα in predicting the efficacy of ADA in AS. MATERIALS AND METHODS: Eighty patients with active AS who received ADA treatment were followed up for 24 weeks. Six known SNPs of TNFα (+489G/A, -238G/A, -308G/A, -857C/T, -863C/A, and -1031C/T) were subjected to the SNaPshot SNP typing method, which has been proven to be a reliable, efficient, and cost-effective method for detecting SNPs. The relationship between each SNP genotype and the therapeutic efficacy of ADA was analyzed. RESULTS: At the end of the 24-week follow-up, 58.8% of the patients with AS achieved Assessment of SpondyloArthritis International Society (ASAS) partial remission (PR), 67.5% of the patients achieved the criteria of an ASAS40 response (40% improvement on indices), and 53.8% of the patients achieved Ankylosing Spondylitis Disease Activity Score (ASDAS) major improvement (MI). The univariate analysis showed that patients with AS carrying the TNFα +489 A allele were more likely to achieve ASAS-PR, ASAS40 response criteria, and ASDAS-MI after ADA treatment. In the multivariate regression analysis, the TNFα +489 A allele was an independent factor influencing the efficacy of ADA in treating AS (ASAS-PR odds ratio (OR) = 2.66, 95% confidence interval (CI) = 1.01-7.01; ASAS40 OR = 4.56, 95% CI = 1.39-15.00; ASDAS-MI OR = 3.31, 95% CI = 1.02-10.69). CONCLUSIONS: The patients carrying the TNFα +489 A allele may be more likely to experience better therapeutic efficacy and achieve the treatment target (ASAS-PR, ASAS40 response, or ASDAS-MI) after receiving ADA treatment. Detection of TNFα +489 G/A may predict the therapeutic efficacy of ADA, which can be used in clinical practice to tailor treatment for individual patients with AS. Further studies with larger sample sizes and longer follow-up periods with imaging evaluation are needed to verify our findings.

Comparison of clinical characteristics between adult-onset and juvenile-onset non-radiographic axial spondyloarthritis in Chinese patients: results from the COCAS cohort.

BACKGROUND: Axial spondyloarthritis (axSpA) is a chronic inflammatory rheumatic disease predominantly affecting the axial skeleton. We aimed to describe the clinical characteristics of patients with non-radiographic axSpA (nr-axSpA) in China and compare the differences between adult- and juvenile-onset cases. METHODS: A cross-sectional study was conducted using data from 776 patients with nr-axSpA in the Clinical Characteristic and Outcome in Chinese Axial Spondyloarthritis (COCAS) study cohort. Patients were divided into two groups including the adult-onset group (n = 662) and the juvenile-onset group (n = 114) according to age at disease onset. Baseline demographics and clinical characteristics were compared between patients with adult-onset and juvenile-onset nr-axSpA. RESULTS: Overall, the male-to-female ratio was 1.26:1, the prevalence of HLA-B27 positivity was 72.2%, and the median age at disease onset of nr-axSpA was 22 years. Nearly 75% of nr-axSpA patients had peripheral arthritis in the disease course, and the prevalence of extra-articular manifestations was 10.4%. The juvenile-onset group contained a higher proportion of men (66.7% vs. 53.9%, P = 0.011) and a longer baseline disease duration (4.0 [4.0] vs. 1.6 [3.5], P < 0.001) than the adult-onset group. A family history of spondyloarthritis was more frequent in the juvenile-onset group than in the adult-onset group (23.7% vs. 15.4%, P = 0.028), but no significant difference in the prevalence of HLA-B27 positivity was observed between the two groups (P = 0.537). Regarding initial symptoms, peripheral arthritis occurred more often in patients with juvenile-onset nr-axSpA, whereas patients with adult-onset nr-axSpA presented more frequently with axial involvement. The prevalence of inflammatory back pain (IBP) was higher in the adult-onset group than in the juvenile-onset group (85.0% vs. 75.4%, P = 0.010), whereas the juvenile-onset group showed a higher prevalence of peripheral arthritis and enthesitis than the adult-onset group (67.5% vs. 48.5%, P < 0.001; 35.1% vs. 23.3%, P = 0.007, respectively). CONCLUSIONS: Compared with adult-onset nr-axSpA, juvenile-onset nr-axSpA was more common in men and those with a family history of spondyloarthritis. Juvenile-onset nr-axSpA presents with a "peripheral predominant" mode at disease onset and a higher frequency of peripheral arthritis and enthesitis during the disease course.

Risk factors for progression of juvenile-onset non-radiographic axial spondyloarthritis to juvenile-onset ankylosing spondylitis: a nested case-control study.

OBJECTIVE: To evaluate the clinical characteristics of juvenile-onset non-radiographic axial spondyloarthritis (nr-axSpA) and to investigate risk factors associated with progression to juvenile-onset ankylosing spondylitis (JoAS). METHODS: A nested case-control study was conducted using the retrospectively collected data of 106 patients with juvenile-onset nr-axSpA (age at disease onset, <16 years) in the Clinical characteristic and Outcome in Chinese Axial Spondyloarthritis study cohort. Baseline demographic and clinical characteristics and prognosis were reviewed. Logistic regression analyses were performed to investigate risk factors associated with progression to JoAS. RESULTS: Overall, 58.5% of patients with juvenile-onset nr-axSpA presented with peripheral symptoms at disease onset. In 82.1% of these patients, axial with peripheral involvement occurred during the disease course. The rate of disease onset at >12 years and disease duration of ≤10 years were significantly higher in those with progression to JoAS than in those without progression to JoAS (83.0% vs 52.8%, p=0.001; 92.5% vs 56.6%, p<0.001, respectively). Multivariable logistic regression analysis revealed that inflammatory back pain (IBP) (OR 13.359 (95% CI 2.549 to 70.013)), buttock pain (OR 10.171 (95% CI 2.197 to 47.085)), enthesitis (OR 7.113 (95% CI 1.670 to 30.305)), elevated baseline C reactive protein (CRP) levels (OR 7.295 (95% CI 1.984 to 26.820)) and sacroiliac joint-MRI (SIJ-MRI) positivity (OR 53.821 (95% CI 9.705 to 298.475)) were significantly associated with progression to JoAS. CONCLUSION: Peripheral involvement was prevalent in juvenile-onset nr-axSpA. IBP, buttock pain, enthesitis, elevated baseline CRP levels and SIJ-MRI positivity in patients with the disease are associated with higher risk of progression to JoAS.

Immunohistological analysis of active sacroiliitis in patients with axial spondyloarthritis.

The sacroiliac joints (SIJs) are one of the most common sites involved in axial spondyloarthritis (axSpA), and there are few studies on the histopathology of the SIJ in this group of patients.Mononuclear cell infiltrates in the bone marrow and fibrous tissue resembling a pannus formation were the pathological features of early sacroiliitis in our previous study. We undertook a further immunohistological evaluation of these features in patients with axSpA.Biopsy specimens from the SIJ of 6 patients with established ankylosing spondylitis (AS) and 13 patients with nonradiographic axial spondyloarthritis (nr-axSpA) were analyzed. An immunohistological method was performed to examine the macrophages (CD163), T cells (CD3), and B cells (CD20).Mononuclear cell infiltrates in the bone marrow were observed in only 6 patients with nr-axSpA. Fibrous tissue was observed in all patients with established AS and 9 patients with nr-axSpA. Macrophage, T cell, and B cell infiltrates could be detected in both the bone marrow and fibrous tissue. All bone marrow specimens from 6 nr-axSpA patients exhibited CD163+ macrophage infiltrates; of these, 5 exhibited CD20+ B cell infiltrates and 3 exhibited CD3+ T cell infiltrates. Among the fibrous tissue specimens, all exhibited macrophage infiltrates, 9 exhibited B cell infiltrates, and 4 exhibited T cell infiltrates.In addition to macrophages and T cells, B cells are also involved in active sacroiliitis in patients with axSpA.

Bone edema on magnetic resonance imaging is highly associated with low bone mineral density in patients with ankylosing spondylitis.

OBJECTIVE: This study aimed to assess the relationship between bone marrow edema (BME) on magnetic resonance imaging (MRI) and bone mineral density (BMD) in patients with ankylosing spondylitis (AS). METHODS: The study included 333 patients with AS who underwent BMD measurements and axial MRI. Additionally, 106 normal controls were included. The modified New York criteria were used as the classification criteria of AS. Clinical, laboratory, and imaging data were collected and analyzed. Lumbar spine and proximal femur BMD were assessed using dual-energy X-ray absorptiometry. Low BMD was defined by a Z-score ≤-2. The Spondyloarthritis Research Consortium of Canada (SPARCC) MRI index was used to assess inflammation at the sacroiliac joint (SIJ) and spine. RESULTS: Among the 333 patients, the male:female ratio was 4.6:1, mean patient age was 28.5±10.6 years, and mean disease duration was 7.3±6.8 years. The prevalences of low BMD, osteopenia, and osteoporosis were significantly higher among AS patients than among controls (19.8%, 62.8%, and 5.7% vs. 4.7%, 33.0%, and 0%, respectively, P = 0.000). The BMD values were significantly lower and prevalences of low BMD at both the spine and femur were significantly higher among patients with BME on MRI than among those without BME. Multivariate logistic regression analysis showed that male sex (OR 3.87, 95% CI 1.21-7.36, P = 0.023), high ASDAS-CRP score (OR 2.83, 95% CI 1.36-4.76, P = 0.015), the presence of BME on sacroiliac MRI (OR 2.83, 95% CI 1.77-6.23, P = 0.000) and spinal MRI (OR 4.06, 95% CI 1.96-8.46, P = 0.000), and high grade of sacroiliitis (OR 2.93, 95% CI 1.82-4.45, P = 0.002) were risk factors for low BMD (any site). The SPARCC scores of the SIJ were negatively correlated with femoral BMD (r = -0.22, 95% CI -0.33 to -0.10, P = 0.000). Additionally, the SPARCC scores of the spine were negatively correlated with BMD values (r = -0.23, 95% CI -0.36 to -0.09, P = 0.003) and Z-scores (r = -0.24, 95% CI -0.36 to -0.12, P = 0.001) at the spine. CONCLUSION: Low BMD is common in AS patients. BME on MRI is highly associated with low BMD at both the spine and femur.

Changes in the Prevalence of Rheumatic Diseases in Shantou, China, in the Past Three Decades: A COPCORD Study.

This study aimed to clarify changes in the prevalence of rheumatic diseases in Shantou, China, in the past 3 decades and validate whether stair-climbing is a risk factor for knee pain and knee osteoarthritis (KOA). The World Health Organization-International League Against Rheumatism Community Oriented Program for Control of Rheumatic Diseases (COPCORD) protocol was implemented. In all, 2337 adults living in buildings without elevators and 1719 adults living in buildings with elevators were surveyed. The prevalence of rheumatic pain at any site and in the knee was 15.7% and 10.2%, respectively; both types of pain had a significantly higher incidence in residents of buildings without elevators than was reported by people who lived in buildings with elevators (14.9% vs. 10.6% and 11.32% vs. 8.82%, respectively) (both P < 0.0001). The prevalence of rheumatic pain in the neck, lumbar spine, shoulder, elbow, and foot was 5.6%, 4.5%, 3.1%, 1.4%, and 1.8%, respectively; these findings were similar to the data from the 1987 rural survey, but were somewhat lower than data reported in the urban and suburban surveys of the 1990s, with the exception of neck and lumbar pain. The prevalence of KOA, gout, and fibromyalgia was 7.10%, 1.08%, and 0.07%, respectively, and their prevalence increased significantly compared with those in previous studies from the 20th century. There were no significant differences in the prevalence of rheumatoid arthritis (RA) (0.35%) or ankylosing spondylitis (AS) (0.31%) compared to that reported in prior surveys. The prevalence of KOA was higher in for residents of buildings without elevators than that in those who had access to elevators (16-64 years, 5.89% vs. 3.95%, P = 0.004; 16->85 years, 7.64% vs. 6.26%, P = 0.162). The prevalence of RA and AS remained stable, whereas that of KOA, gout, and fibromyalgia has increased significantly in Shantou, China, during the past 3 decades. Stair-climbing might be an important risk factor for knee pain and KOA.