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Background: Limited current information exists regarding discospondylitis within breeds commonly affected by congenital vertebral body malformations. Hypothesis/Objectives: Report the prevalence of discospondylitis in English and French bulldogs and investigate for possible associations of discospondylitis with congenital vertebral body malformations. Animals: 108 client‐owned dogs. Methods: Retrospective multi‐institutional study between June 2010 and 2020. Cases with a diagnosis of discospondylitis on computed tomography (CT) or magnetic resonance imaging (MRI) and complete medical records included. Signalment, discospondylitis location, presence of congenital vertebral body malformations, and the site of maximal kyphosis were recorded. Results: The prevalence of discospondylitis was 3.4 (1.6‐6.7, 95% confidence interval [CI]) times higher in French bulldogs (P <.001) and 4.3 (1.7‐9.8, 95% CI) times higher in English bulldogs (<.001), compared with the overall hospital cohort. One or more vertebral malformations were present in 12 French bulldogs (92.3%), 6 English bulldogs (75.0%), and 1 "other" breed dog (1.1%). Discospondylitis was diagnosed adjacent to congenital vertebral body malformations in 12 (80%) intervertebral discs in French bulldogs and 5 (50%) intervertebral discs in English bulldogs. The median age at presentation was significantly younger in French bulldogs (1.1 years; range, 0.5‐9.2 years) and English bulldogs (1.0 years; range, 0.4‐7.0 years), compared with "other" breed dogs (7.3 years; range, 0.3‐14.0 years; both P <.001). Conclusions and Clinical Importance: Congenital vertebral body malformations were frequently associated with discospondylitis in French and English bulldogs, with clinical signs commonly encountered at a significantly younger age. [ABSTRACT FROM AUTHOR]

Hydrogels are notable for their outstanding absorbent qualities, satisfactory compatibility with biological systems, ability to degrade, and inherent safety, all of which contribute to their high demand in the field of biomedicine. This study focuses on the fabrication of hydrogels using environmentally friendly cellulosic material. Cellulose hydrogel beads were prepared by physical cross‐linking in a NaOH/urea medium. Furthermore, nano polydopamine was integrated into the hydrogel matrix as functional polymers and α‐mangostin was employed as an active pharmaceutical ingredient. The physicochemical properties were comprehensively analyzed using Fourier‐transform infrared spectrometer, 13C cross‐polarization/magic angle spinning nuclear magnetic resonance, thermogravimetric analysis, and scanning electron microscope. The drug delivery properties, including water content, swelling ratio, and drug release profiles, were evaluated. In vitro cytotoxicity against MC3T3‐E1 cells was assessed using sulforhodamine B staining. All test hydrogels exhibited inhibitory activity against the growth of MC3T3‐E1 cells. These results indicated the potential use of these hydrogels as a drug delivery carrier for α‐mangostin in the treatment of ankylosing spondylitis. [ABSTRACT FROM AUTHOR]

Acute anterior uveitis (AAU) is a common extra‐articular manifestation of ankylosing spondylitis (AS), particularly in patients positive for the human leucocyte antigen (HLA)‐B27 genetic marker. To explore the underlying mechanisms of HLA‐B27+ AS‐associated AAU, we employed single‐cell RNA sequencing to profile the transcriptomes of peripheral blood mononuclear cells in three HLA‐B27+ AS‐associated AAU patients and three healthy controls (HCs). We identified 11 distinct immune cell clusters, with a particular focus on monocytes, revealing six subsets, including three previously unidentified subsets, namely, GTPase immune‐associated proteins, Th17‐related, and lncRNA monocytes, with unique gene expression patterns. Significant differences in monocyte composition, activation states, and gene expression were observed between patients and HCs, particularly within HLA monocyte subpopulations. Notably, enhanced expression of X‐inactive specific transcript and myeloid cell nuclear differentiation antigen genes was validated across monocyte subclusters in patients. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis highlighted significant enrichment in antigen processing and presentation pathways, shedding light on the disease's molecular mechanisms. These findings provide novel insights into the molecular mechanisms of HLA‐B27+ AS‐associated AAU and may contribute to the development of targeted diagnostic and therapeutic strategies. Further clinical validation is essential. [ABSTRACT FROM AUTHOR]

Background: IL‐23 inhibitors were recently approved for the treatment of skin psoriasis and psoriatic arthritis (PsA). Risankizumab, a humanized monoclonal antibody that specifically binds the p19 subunit of IL‐23, has proven effective on PsA in two randomized controlled trials. To date, only a few real‐world data are available on this topic. Methods: Our study aimed to prospectively evaluate the effectiveness of risankizumab in patients with PsA in a real‐world setting. For this purpose, both rheumatologic and dermatologic assessments were performed at baseline and after 28–40 weeks of continuous risankizumab administration. Moreover, joint and entheses ultrasound assessment was performed at the mentioned time points. The rheumatologic assessment was carried out by means of the following scores: (i) clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA); (ii) Leeds Enthesitis Index (LEI); (iii) Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and (iii) Bath Ankylosing Spondylitis Functional Index (BASFI). The degree of skin involvement was measured by both the Psoriasis Area and Severity Index (PASI) and Physician Global Assessment (PGA). Quality of life was assessed by the Health Assessment Questionnaire (HAQ) and Dermatology Life Quality Index (DLQI). Ultrasound assessment of joints and entheses was performed on the basis of the EULAR‐OMERACT score. Results: After treatment, cDAPSA decreased from a mean value of 12.9 ± 7.6 to 7.0 ± 6.1 (P < 0.001), and the median PD score significantly decreased from baseline (3; range 1–8) to TP1 (1; range 0–7) (P < 0.001). PASI score also decreased from 8.4 ± 4.9 to 0.3 ± 0.5 (P < 0.001), and PGA from 3.1 ± 1.0 to 0.4 ± 0.5 (P < 0.001). Conclusion: We can conclude that risankizumab led to substantial improvement in both skin and joint involvement. [ABSTRACT FROM AUTHOR]

Objective: This study aims to comprehensively investigate immune‐cell landscapes in ankylosing spondylitis (AS) patients and explore longitudinal immunophenotyping changes induced by biological agents. Methods: We employed mass cytometry with 35 cellular markers to analyze blood samples from 34 AS patients and 13 healthy controls (HC). Eleven AS patients were re‐evaluated 1 month (4 patients) and 3 months (7 patients) after treatment with biological agents. Flow Self‐Organizing Maps (FlowSOM) clustering was performed to identify specific cellular metaclusters. We compared cellular abundances across distinct subgroups and validated subset differences using gating strategies in flow cytometry scatter plots, visualized with FlowJo software. The proportions of differential subsets were then used for intercellular and clinical correlation analysis, as well as for constructing diagnostic models based on the random forest algorithm. Results: In AS patients, we identified and validated nine different immune‐cell subsets compared to HC. Three subsets increased: helper T‐cell 17 (Th17), mucosa‐associated invariant T‐cell (MAIT), and classical monocytes (CM). Six subsets decreased: effector memory T‐cell (TEM), naïve B cells, transitional B cells, IL10+ memory B cells, non‐classical monocytes (NCM), and neutrophils. Treatments with biological agents could rectify cellular abnormalities, particularly the imbalance of CM/NCM. Furthermore, these subsets may serve as biomarkers for assessing disease activity and constructing effective diagnostic models for AS. Conclusion: These findings provide novel insights into the specific patterns of immune cell in AS, facilitating the further development of novel biomarkers and potential therapeutic targets for AS patients. [ABSTRACT FROM AUTHOR]

The article discusses a case report of a 40-year-old female patient diagnosed with both multiple sclerosis (MS) and ankylosing spondylitis (AS) who was successfully treated with ocrelizumab. AS is a systemic inflammatory disorder primarily affecting the axial skeleton, while MS is a chronic demyelinating disorder of the central nervous system. The patient experienced significant improvement in both AS and MS symptoms with ocrelizumab treatment, achieving inactive disease status with no reported adverse effects. This case highlights the potential benefits of ocrelizumab in treating patients with dual diagnoses of AS and MS, although further research is needed to fully understand its safety and efficacy profile. [Extracted from the article]

Aim: This study investigates changes in immune cell subsets in peripheral blood of ankylosing spondylitis (AS) patients with colitis or terminal ileitis. It aims to explore the connection between changes in lymphocyte subsets and gut inflammation, providing insights for early detection. Methods: Overall, 50 AS patients undergoing colonoscopy were enrolled. Flow cytometry was employed to analyze lymphocyte subsets, including T and B cells, in peripheral blood. Disease activity was assessed using CRP, ESR, BASDAI, ASDAS‐CRP, and ASDAS‐ESR. Results: Compared to AS patients without gut inflammation, those with colorectal inflammation showed a significant increase in total T cells (p <.05), an increase in exhausted CD4+ T cells (p <.05), and a decrease in Th2 cells and total Tc cells (p <.05). Notably, in AS patients with terminal ileitis, there was an increase in total B cells and classic switched B cells (p <.05), with a decrease in double‐positive T cells (p <.05). However, no significant differences were observed in the distribution of Tfh‐cell subpopulations (Tfh1, Tfh2, Tfh17) and Tc‐cell subpopulations (Tc1, Tc2, Tc17) between AS patients with either colorectal inflammation or terminal ileitis (p >.05). We explored the relationship between disease activity scores, ESR, CRP, and lymphocyte subsets, but found no statistically significant correlation between them. Conclusion: Distinct immune patterns may exist in AS with different types of intestinal inflammation. Colitis in AS is primarily characterized by a significant increase in exhausted CD4+ T cells, along with a decrease in Th2 cells. In contrast, terminal ileum inflammation in AS is marked by an increase in total B cells and classic switched B cells. These findings offer new insights for early detection and therapeutic intervention. [ABSTRACT FROM AUTHOR]

Aim: Ankylosing spondylitis (AS) predominantly affects the spine and sacroiliac joints, with rare renal involvement. We investigated the incidence rate and risk factors for chronic kidney disease (CKD) in patients with AS and its relationship with long‐term nonsteroidal anti‐inflammatory drug (NSAID) use. Methods: We retrospectively analyzed data of patients diagnosed with AS from the Korean National Health Insurance service. The 3‐month, 6‐month, and 1‐year Assessment of SpondyloArthritis International Society (ASAS) NSAID Intake Scores were categorized into four groups, as follows: =0, >0 and ≤33.3, 33.3–66.6, and >66.6. Results: Of the 12 000 patients with AS, 150 were identified with CKD, and the incidence rate was 4.64 per 10 000 patient‐years. Factors significantly associated with CKD included age ≥60 years, Charlson Comorbidity Index, hypertension, and diabetes mellitus. In the nested case–control analysis, among the ASAS NSAIDs Intake Scores for 0–365 days from diagnosis, the ≥66.6 group had a significantly lower odds ratio than those of the =0 group. Conclusion: The present study established the incidence rate of CKD in Korean patients with AS. Though older age and comorbidities were found to be associated with a higher CKD risk, long‐term NSAID use was associated with a lower risk. Therefore, the optimal use of NSAIDs in inflammatory diseases requires extensive research. [ABSTRACT FROM AUTHOR]

Vaccine‐associated rheumatic diseases are rare but one of the most feared adverse drug reactions (ADRs). However, this topic has been investigated less with large‐scale data in the literature. With the rapid progress in the development and approval of vaccines during the pandemic, public concerns regarding their safety have been raised. To assess the global and regional burden, long‐term trends, and potential risk factors of vaccines‐associated six types of rheumatic diseases (ankylosing spondylitis [AS], polymyalgia rheumatica [PMR], rheumatoid arthritis [RA], Sjögren's syndrome, Systemic lupus erythematosus [SLE], Systemic scleroderma), this study conducted disproportionality analysis based on the reports from the World Health Organization International Pharmacovigilance Database documented between 1967 and 2023 (n for total reports = 131 255 418) across 156 countries and territories. We estimated the reporting odds ratio (ROR) and information component (IC) to determine the disproportionality signal for rheumatic diseases. Of 198 046 reports of all‐cause rheumatic diseases, 14 703 reports of vaccine‐associated rheumatic diseases were identified. While the reporting counts have gradually increased over time globally, we observed a dramatic increase in reporting counts after 2020, potentially due to a large portion of reports of COVID‐19 mRNA vaccine‐associated rheumatic diseases. The disproportionality signal for rheumatic diseases was most pronounced in HBV vaccines (ROR, 4.11; IC025, 1.90), followed by COVID‐19 mRNA (ROR, 2.79; IC025, 1.25), anthrax (ROR, 2.52; IC025, 0.76), papillomavirus (ROR, 2.16; IC025, 0.95), encephalitis (ROR, 2.01; IC025, 0.58), typhoid (ROR, 1.91; IC025, 0.44), influenza (ROR, 1.49; IC025, 0.46), and HAV vaccines (ROR, 1.41; IC025, 0.20). From age‐ and sex‐specific perspective, young females and old males are likely to have vaccine‐associated rheumatic disease reports. Furthermore, overall vaccines showed a disproportionality signal for PMR (IC025, 3.13) and Sjögren's syndrome (IC025, 0.70), systemic scleroderma (IC025, 0.64), specifically while the COVID‐19 mRNA vaccines are associated with all six types of diseases. Although multiple vaccines are associated with rheumatic disease reports, healthcare providers should be aware of the potential of autoimmune manifestations following vaccination, particularly the COVID‐19 mRNA and HBV vaccines, and take into account for risk factors associated with these ADRs. Most ADRs exhibited an average time to onset of 11 days, underscoring the significance of monitoring and timely management by clinicians. [ABSTRACT FROM AUTHOR]

Clinical Key Message: In patients receiving anti‐TNF‐α drugs for ankylosing spondylitis, monitoring purpuric and ischemic skin lesions is crucial. This case underscores the significance of identifying and addressing drug‐induced vasculitis while stressing the necessity for prompt evaluation and exploration of alternative treatment options to safeguard patient well‐being. The case discusses a 38‐year‐old female with a history of ankylosing spondylitis (AS) who presented with skin lesions, including purpuric skin lesions and ischemia of her right foot digits, after initiating treatment with adalimumab. After excluding other potential causes, such as infections and malignancies, the patient received a diagnosis of moderate‐sized vascular vasculitis associated with adalimumab use. Discontinuation of adalimumab and treatment with high dose glucocorticoids and intravenous pulse of cyclophosphamide resulted in the resolution of her ischemic lesions. This case underscores the importance of considering drug‐related side effects in patients with new skin lesions, particularly in the context of rheumatic diseases such as AS. [ABSTRACT FROM AUTHOR]

Background: N6‐methyladenosine (m6A) has been identified as the most abundant modification of RNA molecules and the aberrant m6A modifications have been associated with the development of autoimmune diseases. However, the role of m6A modification in ankylosing spondylitis (AS) has not been adequately investigated. Therefore, we aimed to explore the significance of m6A regulator‐mediated RNA methylation in AS. Methods: The methylated RNA immunoprecipitation sequencing (meRIP‐seq) and digital RNA sequencing (Digital RNA‐seq) were conducted using the peripheral blood mononuclear cells from three AS cases and three healthy controls, to identify genes affected by abnormal RNA methylation. The genes associated with different peaks were cross‐referenced with AS‐related genes obtained from the GeneCards Suite. Subsequently, the expression levels of shared differentially expressed genes (DEGs) and key m6A regulators in AS were evaluated using data from 68 AS cases and 36 healthy controls from two data sets (GSE25101 and GSE73754). In addition, the results were validated through quantitative polymerase chain reaction (qPCR). Results: The meRIP‐seq and Digital RNA‐seq analyses identified 28 genes with upregulated m6A peaks but with downregulated expression, and 52 genes with downregulated m6A peaks but with upregulated expression. By intersecting the genes associated with different peaks with 2184 AS‐related genes from the GeneCards Suite, we identified a total of five shared DEGs: BCL11B, KAT6B, IL1R1, TRIB1, and ALDH2. Through analysis of the data sets and qPCR, we found that BCL11B and IL1R1 were differentially expressed in AS. Moreover, two key m6A regulators, WTAP and heterogeneous nuclear ribonucleoprotein C, were identified. Conclusions: In conclusion, the current study revealed that m6A modification plays a crucial role in AS and might hence provide a new treatment strategy for AS disease. [ABSTRACT FROM AUTHOR]

The pathogenesis of ankylosing spondylitis (AS) remains unclear, and while recent studies have implicated necroptosis in various autoimmune diseases, an investigation of its relationship with AS has not been reported. In this study, we utilized the Gene Expression Omnibus database to compare gene expressions between AS patients and healthy controls, identifying 18 differentially expressed necroptosis‐related genes (DENRGs), with 8 upregulated and 10 downregulated. Through the application of three machine learning algorithms—least absolute shrinkage and selection operation, support vector machine‐recursive feature elimination and random forest—two hub genes, FASLG and TARDBP, were pinpointed. These genes demonstrated high specificity and sensitivity for AS diagnosis, as evidenced by receiver operating characteristic curve analysis. These findings were further supported by external datasets and cellular experiments, which confirmed the downregulation of FASLG and upregulation of TARDBP in AS patients. Immune cell infiltration analysis suggested that CD4+ T cells, CD8+ T cells, NK cells and neutrophils may be associated with the development of AS. Notably, in the group with high FASLG expression, there was a significant infiltration of CD8+ T cells, memory‐activated CD4+ T cells and resting NK cells, with relatively less infiltration of memory‐resting CD4+ T cells and neutrophils. Conversely, in the group with high TARDBP expression, there was enhanced infiltration of naïve CD4+ T cells and M0 macrophages, with a reduced presence of memory‐resting CD4+ T cells. In summary, FASLG and TARDBP may contribute to AS pathogenesis by regulating the immune microenvironment and immune‐related signalling pathways. These findings offer new insights into the molecular mechanisms of AS and suggest potential new targets for therapeutic strategies. [ABSTRACT FROM AUTHOR]

Ankylosing spondylitis (AS) is a chronic inflammatory arthritis affecting the spine, presenting a considerable morbidity risk. Although evidence consistently indicates an elevated risk of ischemic heart disease among AS patients, debates persist regarding the likelihood of these patients developing left ventricular dysfunction (LVD). Our investigation aimed to determine whether individuals with AS face a greater risk of LVD compared to the general population. To accomplish this, we identified studies exploring LVD in AS patients across five major databases and Google Scholar. Initially, 431 studies were identified, of which 30 met the inclusion criteria, collectively involving 2933 participants. Results show that AS patients had: (1) poorer Ejection Fraction (EF) [mean difference (MD): −0.92% (95% CI: −1.25 to −0.59)], (2) impaired Early (E) and Late (atrial—A) ventricular filling velocity (E/A) ratio [MD: −0.10 m/s (95% CI: −0.13 to −0.08)], (3) prolonged deceleration time (DT) [MD: 12.30 ms (95% CI: 9.23–15.36)] and, (4) a longer mean isovolumetric relaxation time (IVRT) [MD: 8.14 ms (95% CI: 6.58–9.70)] compared to controls. Though AS patients show increased risks of both systolic and diastolic LVD, we found no significant differences were observed in systolic blood pressure [MD: 0.32 mmHg (95% Confidence Interval (CI): −2.09 to 2.73)] or diastolic blood pressure [MD: 0.30 mmHg (95% CI: −0.40 to 1.01)] compared to the general population. This study reinforces AS patients' susceptibility to LVD without a notable difference in HTN risk. [ABSTRACT FROM AUTHOR]

Objectives: To describe the clinical outcome of dogs diagnosed with concurrent discospondylitis/vertebral physitis and congenital intrahepatic portosystemic shunts. Materials and Methods: Medical records from two academic institutions were searched for dogs diagnosed with discospondylitis and/or vertebral physitis, and a concurrent intrahepatic portosystemic shunt. Dogs were excluded if they did not undergo attenuation of their shunt, did not have a single congenital intrahepatic shunt and did not have at least 90 days of follow‐up. Results: Six dogs met the inclusion criteria and were included in the study. Discospondylitis alone was diagnosed in four dogs, vertebral physitis alone in one dog and both discospondylitis and vertebral physitis in one dog. Three dogs had a right divisional intrahepatic portosystemic shunt, and three dogs had a left divisional intrahepatic portosystemic shunt. Median duration of antimicrobial therapy was 112 days (range 14 to 240 days). Clinical resolution of discospondylitis and vertebral physitis was noted in all dogs. Endovascular attenuation was performed in all dogs a median of 82 days after presentation (range 1 to 317 days). No perioperative or postoperative complications occurred. All dogs were alive at the last available follow‐up a median of 513 days after presentation (range 224 to 1504 days) and free of clinical signs associated with discospondylitis or vertebral physitis, as well as their portosystemic shunt. Clinical Significance: Dogs with intrahepatic portosystemic shunts may concurrently develop discospondylitis and vertebral physitis. With antimicrobial therapy and endovascular embolisation of their portosystemic shunt, all dogs in this study had a good outcome with clinical resolution of both disease processes. However, long‐term follow‐up was not obtained in all cases. [ABSTRACT FROM AUTHOR]

Objectives: Ankylosing spondylitis (AS) can cause peripheral arthritis, tendinitis, enthesitis, and axial skeletal involvement. This study aims to determine early tendon damage by shear wave elastography (SWE) for the Achilles tendon in AS patients. Methods: 48 AS patients and 48 asymptomatic individuals were included in the study. Participants were systematically examined with B‐mode, power Doppler, and SWE using a high‐resolution linear 6–15 MHz probe. Bilateral Achilles tendon stiffness, thickness, and vascularity were evaluated. Measurements were taken from the middle third of the Achilles tendon in the sagittal plane. Difference between the two groups was evaluated with statistical methods. Receiver operating characteristic analysis was performed to test the diagnostic performance of Achilles tendon stiffness. Additionally, the Spearman correlation test examined the relationship between Achilles tendon stiffness and disease duration. Results: The difference between the two groups regarding Achilles tendon stiffness was statistically significant (p < 0.05). It was observed that Achilles tendon stiffness decreased in the patient group compared with the control group. The diagnostic value of Achilles tendon stiffness measured by SWE was found to be high. A negative correlation was detected between disease duration and tendon stiffness (p < 0.05). Conclusion: In patients diagnosed with AS, deterioration in the Achilles tendon structure was observed, and a significant decrease in tendon stiffness compared with the healthy population. It has been determined that these changes in the Achilles tendon are related to the duration of the disease. [ABSTRACT FROM AUTHOR]

Genome‐wide association studies analysis has revealed associations between ankylosing spondylitis (AS) and loci on the TBX21 gene across various populations. This study aimed to investigate if there is a connection between a higher risk of AS in a Chinese population and two polymorphism loci on the TBX21 gene. To achieve this, we performed a case–control investigation involving 363 patients with AS and 907 healthy individuals. Genotyping was carried out using the iPLEX Gold genotyping assay. The analysis of genotypes and haplotypes was performed using SPSS 23.0 and SHEsis software. The results revealed no statistically significant correlation between the two specified single‐nucleotide polymorphisms of TBX21 (rs11657479 C/T and rs4794067 C/T) and susceptibility to AS. However, upon conducting stratification analysis, our findings demonstrated a significant association between rs11657479 and susceptibility to human leucocyte antigen (HLA)‐B27+ AS in allelic (C vs. T: odds ratio [OR] = 1.52, 95%CI = 1.09–2.11, corrected p [pc] =.028), heterozygous (CT vs. TT: OR = 1.63, 95%CI = 1.13–2.34, pc =.016) and dominant (CT + CC vs. TT: OR = 1.60, 95%CI = 1.12–2.28, pc =.018) models. Furthermore, the haplotype rs4794067/C‐rs11657479/C of TBX21 was found to increase the risk of HLA‐B27+ AS cases. In conclusion, our findings indicate a correlation between TBX21 gene polymorphism and HLA‐B27+ AS patients within the Chinese population. [ABSTRACT FROM AUTHOR]

Objective: Alterations in gut microbiota have been implicated in the pathogenesis of ankylosing spondylitis (AS), but the underlying mechanisms remain elusive. This study aims to investigate changes in gut microbiota and metabolites in individuals with AS before and after treatment with secukinumab, to identify the biological characteristics specific to AS patients and investigate the potential biomarkers, for optimizing therapeutic strategies more effectively. Methods: Fecal microbiome data were collected from 30 AS patients before and after secukinumab therapy and compared with data from 40 healthy controls (HC). Additionally, we analyzed the metabolic profile of both groups from plasma. Results: Findings indicated that the treatment‐induced changes in the composition of several crucial bacterial groups, including Megamonas, Prevotella_9, Faecalibacterium, Roseburia, Bacteroides, and Agathobacter. Post‐treatment, these groups exhibited a distribution more akin to that of the healthy populations compared with their pretreatment status. We identified three gut microbial taxa, namely Prevotellaceae_bacterium_Marseille_P2831, Prevotella_buccae, and Elusimicrobiota, as potential biomarkers for diagnosing individuals at a higher risk of developing AS and assessing disease outcomes. Plasma metabolomics analysis revealed 479 distinct metabolites and highlighted three disrupted metabolic pathways. Integration of microbiome and metabolomics datasets demonstrated a significant degree of correlation, underscoring the impact of the microbiome on metabolic activity. Conclusion: Secukinumab can restore the balance of the gut microbiome and metabolites in AS patients, rendering them more similar to those found in the healthy population. The analysis of microbiome and metabolomics data have unveiled some candidate biomarkers capable of evaluating treatment efficacy. [ABSTRACT FROM AUTHOR]

Objective: This study aims to investigate the potential mechanisms by which the Hangqin Qingrechubi capsule (HQC) improves immunoinflammation in Ankylosing Spondylitis (AS). Methods: The study combines systemic network pharmacology to predict, identify, and validate the core targets of HQC and AS. We conducted molecular docking to validate the interaction between the key active ingredients of HQC and the selected core targets associated with the PI3K/AKT signaling pathway, and employed data mining to delve deeper into the correlation between HQC usage and the improvement of clinical immunoinflammatory indicators. Additionally, AS‐PBMCs and FLS co‐culture cell models will be employed to further explore the mechanism of action of HQC in improving AS immune inflammation. Results: Based on network pharmacology core target prediction, TNF‐α, IL‐17A, IL‐6, IL‐10, and AKT1 were identified as core targets, and KEGG enrichment analysis suggested that PI3K/AKT, IL‐17, and TNF might be key signaling pathways of HQC in improving immune inflammation in AS. The results of molecular docking demonstrated a favorable binding energy between the selected AKT1 core target and the key active components of HQC, including baicalin, baicalein, and quercetin. Clinical data mining revealed a significant correlation between HQC use and improvement in clinical immunoinflammatory indexes, such as ESR, CRP, IgA, IgM, IgG, C3, C4, patient perception scores (VAS, SAS, SDS), and (PF, SF) scores. In vitro cellular experiments further supported the significant ability of HQC to inhibit PI3K/AKT signaling pathway activation. Conclusion: HQC, as an herbal compound preparation, exhibits anti‐inflammatory effects through multiple components and targets, making it a potential treatment option for AS. Furthermore, an underlying mechanism of action of HQC is its ability to ameliorate immune inflammation in AS patients by inhibiting the PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Aim: To compare the effects of Yoga with traditional exercise on the mobility and functional capacity of individuals with ankylosing spondylitis (AS). Methods: The participants of the study were recruited at the rheumatology department, adhering to the study's inclusion and exclusion criteria. Participants were randomized into two groups (Group A – Yoga, and Group B – exercise).The candidates participated in an 8‐week intervention consisting of 3 weekly sessions of either Yoga or Exercise intervention. Outcomes were collected at pre‐treatment, at 8 weeks, and at 12 weeks. Results: The within‐group comparison showed an improvement in all outcome measures with p <.05 between post‐treatment and the follow‐up. In the yoga group, there was an improvement in the measures of BASMI (p =.001), BASFI (p =.005), PSQI (p =.021), CE (p =.053) and NPRS (p =.001). Similarly, in the exercise group, there was an improvement in BASMI (p =.002), BASFI (p =.003), PSQI (p =.010), CE (p =.004) and NPRS (p =.001). In the between group comparison at post‐treatment, there were no statistically significant differences in BASMI (yoga = 3.0 ± 1.50, exercise = 2.3 ± 1.38), PSQI (yoga = 5.3 ± 1.50, exercise = 4.9 ± 1.17) and NPRS (yoga = 1.3 ± 2.22, exercise = 0.4 ± 0.50) CE (yoga = 4.0 ± 1.18, exercise = 3.4 ± 0.96), BASFI (yoga = 1.8 ± 2.14, exercise = 2.1 ± 1.87). Conclusion: The results demonstrated a statistically significant improvement in within‐group scores of mobility, functional capacity, sleep quality and pain in AS patients of both intervention programs but there were no significant differences between the groups. [ABSTRACT FROM AUTHOR]

Axial spondyloarthritis (axSpA) is a chronic inflammatory arthritis that primarily affects the spine and is often associated with inflammatory bowel disease (IBD). This case report discusses a 19-year-old patient who presented with refractory axSpA and IBD. Despite previous treatments, the patient experienced persistent symptoms until upadacitinib, a Janus kinase inhibitor, was introduced. The patient showed significant improvement in symptoms and disease activity with upadacitinib treatment. This case suggests that upadacitinib may be a viable option for patients with refractory axSpA and IBD. [Extracted from the article]

Key Clinical Message: Administering azathioprine or infliximab for UC and AS treatment carries a significant risk of adverse reactions. Here, we present the case diagnosed with UC and AS, who received treatment with azathioprine and infliximab for 10 months, and subsequently developed drug‐induced myopathy affecting the right vastus medialis muscle. Drug‐induced myopathy is an uncommon form of muscle injury that can arise in patients without preexisting muscle conditions when exposed to therapeutic doses of certain medications. Administering azathioprine or infliximab for ulcerative colitis (UC) and ankylosing spondylitis (AS) treatment carries a significant risk of adverse reactions, including drug‐induced myopathy and increased susceptibility to opportunistic infections. However, occurrences of myopathy induced by the combination of azathioprine and infliximab are rarely reported in clinical practice. Here, we present the case of a 37‐year‐old male patient diagnosed with UC and AS, who received treatment with azathioprine and infliximab for 10 months. Despite the resolution of symptoms and improvement in intestinal mucosal inflammation observed via endoscopy, the patient subsequently developed drug‐induced myopathy affecting the right vastus medialis muscle. [ABSTRACT FROM AUTHOR]

Introduction: The identification of novel, easily measurable disease biomarkers might enhance the diagnosis and management of patients with rheumatic diseases (RDs). We conducted a systematic review and meta‐analysis of ischemia‐modified albumin (IMA), a marker of oxidative stress, acidosis, and ischemia, in RD patients and healthy controls. Methods: We searched PubMed, Web of Science, and Scopus from inception to January 15, 2024. The risk of bias and the certainty of evidence were assessed using the Joanna Briggs Institute Critical Appraisal Checklist and GRADE, respectively. Results: In 20 studies investigating a total of 1188 RD patients (mean age 45 years, 64% females) and 981 healthy controls (mean age 44 years, 66% females), RD patients had significantly higher IMA concentrations when compared to controls (standard mean difference, SMD = 0.50, 95% CI: 0.18−0.83, p =.003; I2 = 92.4%, p <.001; low certainty of evidence). In subgroup analysis, the pooled SMD was significantly different in studies investigating ankylosing spondylitis (p <.001), Behçet's disease (p <.001), and rheumatoid arthritis (p =.033), but not familial Mediterranean fever (p =.48). Further associations were observed between the pooled SMD and the broad classification of autoimmune and/or autoinflammatory diseases, the study country, and the method used to measure IMA. Conclusion: Our study suggests that IMA is a promising biomarker of oxidative stress, acidosis, and ischemia, as it can effectively discriminate between patients with different types of RDs and healthy controls. Our results warrant confirmation in longitudinal studies of patients with different types of RDs and different ethnicities (PROSPERO registration number: CRD42024509126). [ABSTRACT FROM AUTHOR]

This article discusses a case report of a 56-year-old female with pulmonary artery hypertension (PAH) secondary to synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome. The patient had a history of joint pain and skin symptoms associated with SAPHO syndrome, and her PAH symptoms worsened over time. After treatment with a Janus kinase (JAK) inhibitor, the patient experienced improvement in her joint pain and shortness of breath. This case highlights the importance of considering PAH as a potential complication of SAPHO syndrome and suggests that JAK inhibitors may be effective in treating this condition. [Extracted from the article]

Background: Vertebral infections, including vertebral osteomyelitis, septic physitis, and discospondylitis, are rarely reported in goats, and when reported, have been largely limited to necropsy case reports. Objective: Describe clinical findings and outcome in goats with vertebral infections evaluated by computed tomography (CT). Animals: Five goats with vertebral osteomyelitis, septic physitis, and discospondylitis evaluated by CT. Methods: Retrospective case series. Results: The most common presenting complaints were progressive weakness, paresis and recumbency. Three goats were tetraparetic and 2 goats had pelvic limb paraparesis. Clinicopathologic findings included leukocytosis, mature neutrophilia, and hyperfibrinogenemia. The most common vertebrae affected were C7‐T1. All 5 goats had discospondylitis with or without vertebral osteomyelitis and septic physitis. Computed tomographic evidence of spinal cord compression was present in 4/5 goats. Medical management (antimicrobials, physical therapy, analgesia, supportive care) was attempted in 4 goats, and 1 goat was euthanized at the time of diagnosis. All 4 goats that were treated regained ambulatory ability and survived to hospital discharge. Conclusions and Clinical Importance: Despite severity of CT imaging findings, goats with discospondylitis, septic physitis, and vertebral osteomyelitis can successfully return to ambulatory function. Additional studies are required to determine ideal treatment regimens. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Ankylosing spondylitis (AS) presents with renal failure and proteinuria in a minority of cases, usually due to secondary amyloidosis or IgA nephropathy. While focal segmental glomerulosclerosis (FSGS) is less common, it should still be in the differential regardless of the patient's clinical profile. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the nail units of patients with axial spondyloarthritis (ax‐SpA) using ultrasound and to identify any subclinical changes. We also aimed to examine the relationship between clinical enthesitis scores and nail involvement in patients with ax‐SpA. Methods: The study included 40 patients with ax‐Spa, 40 patients with psoriatic arthritis (PsA), and 40 healthy controls. The thickness of the nail plates, morphological changes, the thickness of the proximal nail units, the thickness of the nail beds, and power Doppler signal intensities were evaluated and compared. Maastricht Ankylosing Spondylitis Enthesitis Score and Spondyloarthritis Research Consortium of Canada Enthesitis Index were also evaluated in patients with ax‐SpA. Results: There was no significant difference between the thickness of the nail plates of the three groups (P >.05). The first nail bed thickness of ax‐SpA cases was significantly higher than the control group (P =.046), and the fourth and fifth nail proximal unit thicknesses of the control group were significantly lower than the ax‐SpA and PsA groups (P =.023, P =.017). We also found that the Wortsman scores of the cases with PsA were significantly higher than the ax‐SpA and control groups (P =.0001). Conclusion: The thickness of the proximal nail unit adjacent to the insertion of the digital extensor tendon, which is considered as the enthesis area, is similar to the patients with PsA in patients with ax‐SpA, especially in the fourth and fifth fingers compared to the control group. On the other hand, almost no structural changes in nail plates were observed in patients with ax‐SpA group. [ABSTRACT FROM AUTHOR]

Objective: The study objective was to describe patterns of depression and anxiety health care use before and after diagnosis among patients with inflammatory arthritis (IA), namely, ankylosing spondylitis, psoriatic arthritis, and rheumatoid arthritis. Methods: We used population‐based linked administrative health data from British Columbia, Canada, to build a cohort of individuals (≥18 years) with incident IA and individuals without IA ("IA‐free controls") matched on age and sex. We computed the proportion of individuals with IA and controls who had one or more depression or one or more anxiety health care encounters and the use of one or more antidepressants or one or more anxiolytics in each yearly interval five years before and after IA diagnosis. We used multivariable logistic regression models to evaluate the association between IA status and aforementioned depression and anxiety health care use outcomes in each yearly interval. Results: A total of 80,238 individuals with IA (62.9% female; mean ± SD age 56.2 ± 16.7 years) and 80,238 IA‐free controls (62.9% female; mean ± SD age 56.2 ± 16.6 years) were identified between January 1, 2001, and March 31, 2018. Individuals with IA had significantly increased odds of depression and anxiety health care encounters and dispensation of antidepressants and anxiolytics for each yearly interval before and after diagnosis. Adjusted odds ratios (ORs) were highest in the year immediately before (one or more depression visits: adjusted OR 1.61, 95% confidence interval [CI] 1.55–1.66; one or more anxiolytics: adjusted OR 1.71, 95% CI 1.66–1.77) or after (one or more antidepressants: adjusted OR 1.95, 95% CI 1.89–2.00) IA diagnosis. Conclusion: Findings suggest a role for depression and anxiety in characterizing the IA prodrome period and generate hypotheses regarding overlapping biopsychosocial processes that link IA and mental health comorbidities. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Although the concurrent occurrence of vasculitis with AS is uncommon, when patients diagnosed with AS exhibit symptoms including skin petechiae, purpura, abdominal discomfort, malaise, elevated ESR, and reduced complement levels, vigilant monitoring for vasculitis is advisable following the exclusion of secondary vasculitis triggers such as malignancies, infections, and pharmaceutical agents. The primary characteristic of ankylosing spondylitis (AS) involves inflammation occurring within the sacroiliac joint and the spine, leading to destruction and eventual ankylosis. A notably infrequent complication associated with AS is vasculitis, with limited reports linking AS to vasculitis. This case study documents a 48‐year‐old male, diagnosed with HLA‐B27‐positive AS for the past 15 years, who developed abdominal pain and skin lesions following the cessation of his medication on his own. Subsequent clinical evaluations identified leukocytoclastic vasculitis (LCV) related to AS after excluding all other potential causes of LCV, including drug‐related sources, cancer, hepatitis B and C viruses, Henoch‐Schönlein purpura (HSP), and IgA nephropathy. [ABSTRACT FROM AUTHOR]

Background: Ankylosing spondylitis (AS) and Behçet's disease (BD) are distinct inflammatory disorders, but their coexistence is a rare clinical entity. This case sheds light on managing this complex scenario with Janus kinase (JAK) inhibitors. Case Presentation: A 42‐year‐old woman presented with a decade‐long history of lower back pain, nocturnal spinal discomfort, recurrent eye issues, oral and genital ulcers, hearing loss, pus formation in the left eye, and abdominal pain. Multidisciplinary consultations and diagnostic tests confirmed AS (HLA‐B27 positivity and sacroiliitis) and BD (HLA‐B51). Elevated acute‐phase markers were observed. Conclusion: This case fulfills diagnostic criteria for both AS and BD, emphasizing their coexistence. Notably, treatment with upadacitinib exhibited promising efficacy, underscoring its potential as a therapeutic option in patients with contraindications for conventional treatments. Our findings illuminate the intricate management of patients presenting with these two diverse systemic conditions and advocate for further exploration of JAK inhibitors in similar cases. [ABSTRACT FROM AUTHOR]

Objective: Patients with axial spondyloarthritis (axSpA) often experience significant delay between symptom onset and diagnosis for reasons that are incompletely understood. We investigated associations between demographic, medical, and socioeconomic factors and axSpA diagnostic delay. Methods: We identified patients meeting modified New York criteria for ankylosing spondylitis (AS) or 2009 Assessment of Spondyloarthritis International Society criteria for axSpA in the Mass General Brigham health care system between December 1990 and October 2021. We determined the duration of diagnostic delay, defined as the duration of back pain symptoms reported at diagnosis, as well as disease manifestations and specialty care prior to diagnosis from the electronic health record. We obtained each patient's Social Vulnerability Index (SVI) by mapping their address to the US Centers for Disease Control SVI Atlas. We examined associations among disease manifestations, SVI, and diagnostic delay using ordinal logistic regression. Results: Among 554 patients with axSpA who had a median diagnostic delay of 3.8 years (interquartile range 1.1–10), peripheral arthritis (odds ratio [OR] 0.65, 95% confidence interval [CI] 0.45–0.93) and older age at symptom onset (OR 0.83, 95% CI 0.78–0.88 per five years) were associated with shorter delay. AS at diagnosis (OR 1.85, 95% CI 1.30–2.63), a history of uveitis prior to diagnosis (OR 2.77, 95% CI 1.73–4.52), and higher social vulnerability (defined as national SVI 80th to 99th percentiles; OR 1.99, 95% CI 1.06–3.84) were associated with longer diagnostic delay. Conclusion: Older age at back pain onset and peripheral arthritis were associated with shorter delay, whereas uveitis was associated with longer diagnostic delay. Patients with higher socioeconomic vulnerability had longer diagnostic delay independent of clinical factors. [ABSTRACT FROM AUTHOR]

Chronic inflammatory diseases (CIDs) are debilitating and potentially lethal illnesses that affect a large proportion of the global population. Osteopathic manipulative treatment (OMT) is a manual therapy technique developed and performed by osteopathic physicians that facilitates the body's innate healing processes. Therefore, OMT may prove a beneficial anti‐inflammatory modality useful in the management and treatment of CIDs. This work aims to objectively evaluate the therapeutic benefits of OMT in patients with various CIDs. In this review, a structured literature search was performed. The included studies involving asthma, chronic obstructive pulmonary disease, irritable bowel syndrome, ankylosing spondylitis, and peripheral arterial disease were selected for this work. Various OMT modalities, including lymphatic, still, counterstain, and muscle energy techniques, were utilized. Control treatments included sham techniques, routine care, or no treatment. OMT utilization led to variable patient outcomes in individuals with pathologies linked to CID. [ABSTRACT FROM AUTHOR]

This article discusses a case report of a patient who was initially misdiagnosed with ankylosing spondylitis but was later confirmed to have a phosphaturic mesenchymal tumor (PMT). PMT is a rare tumor that can cause a paraneoplastic syndrome characterized by hyperphosphaturia, hypophosphatemia, and osteomalacia. The patient experienced recurrent hip and lower back pain, and despite treatment for ankylosing spondylitis, his symptoms worsened. After surgical excision of the tumor, the patient's symptoms improved and his serological indexes returned to normal. The article emphasizes the importance of considering PMT as a possible diagnosis in patients with hypophosphatemic osteomalacia. [Extracted from the article]

PASS syndrome is a rare autoinflammatory disease characterized by acne vulgaris, hidradenitis suppurativa, pyoderma gangrenosum, and ankylosing spondylitis. Unlike other autoinflammatory disorders such as PAPA and PASH syndrome, there is no documented gene mutation link. Although there are no established treatment guidelines due to the rarity of these diseases, systemic corticosteroids, biologics, and immunosuppressive drugs are used currently. In our report, we presented a case of PASS syndrome who was unresponsive to adalimumab and in whom we observed improvement in both skin and joint manifestations with intravenous immunoglobulin (IVIG) and anti‐IL‐1 treatment. [ABSTRACT FROM AUTHOR]

The article discusses synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, a rare autoinflammatory disease that manifests with articular and cutaneous symptoms. The exact cause of SAPHO syndrome is unknown, but it is believed to have a genetic basis and be linked to underlying infections and immune dysfunction. The syndrome is characterized by extra-articular and cutaneous manifestations, including lung and pleural involvement, digestive tract issues, kidney problems, ocular manifestations, nervous system complications, thrombosis, osteoporosis, sarcopenia, and cardiac manifestations. The article highlights the need for further research to understand the diverse clinical manifestations of SAPHO syndrome. [Extracted from the article]

Ankylosing spondylitis (AS) is an immune chronic inflammatory disease, resulting in back pain, stiffness, and thoracolumbar kyphotic deformity. Based on the reported anti‐inflammatory and antioxidant capacities of cynarin (Cyn), this study explored its protective role and molecular mechanisms in mesenchymal stem cells (MSCs) from AS. The target pathways and genes were verified using Western blotting, quantitative real‐time polymerase chain reaction, and immunofluorescent staining, while molecular docking analysis was conducted. In AS‐MSCs, we found that the expression levels of p‐NF‐κB, IL‐6, IL‐1β, and TNF‐α were higher and IκB‐α, Nrf‐2, and HO‐1 were lower compared with healthy control (HC)‐MSCs. With molecular docking analysis, the biding affinities between Cyn and Keap1‐Nrf‐2 and p65‐IκB‐α were predicted. The mRNA and protein expression of p‐NF‐κB, IL‐6, IL‐1β, and TNF‐α and the reactive oxygen species (ROS) generation were downregulated following Cyn administration. Meanwhile, the expression level of IκB‐α, Nrf‐2, and HO‐1 were significantly increased after Cyn pretreatment. The results suggested that the protective mechanisms of Cyn in AS‐MSCs were based on enhancing the antioxidation and suppression of excessive inflammatory responses via Nrf‐2/ROS/NF‐κB axis. Our findings demonstrate that Cyn is a potential candidate for alleviating inflammation in AS. [ABSTRACT FROM AUTHOR]

Objective: We examined the relationships of work productivity and activity impairment with key patient‐reported outcomes (PROs) assessing pain, disease activity, and health‐related quality of life (HRQoL) in patients with ankylosing spondylitis (AS). Methods: This post hoc analysis pooled available data from baseline to end of the double‐blind phase of phase 2 and 3 placebo‐controlled tofacitinib trials in patients with active AS. A repeated‐measures longitudinal model assessed the relationships (linear or nonlinear) between Work Productivity and Activity Impairment questionnaire in Spondyloarthritis (WPAI:SpA) domains (absenteeism, activity impairment, presenteeism, and productivity loss) as outcomes and key PROs (total back pain, nocturnal spinal pain, Patient Global Assessment of Disease Activity, AS Quality of Life, EuroQol 5‐Dimension 3‐Level [EQ‐5D‐3L], and EQ‐5D Visual Analog Scale [EQ‐5D‐VAS]) as predictors. Results: Data from 330 to 475 patients were available, depending on the analysis. Relationships between WPAI:SpA domains and PROs were approximately linear. The worst PRO scores were associated with a decline in patients' work capacity (measured by activity impairment, presenteeism, and productivity loss [>65%]); the best scores were associated with improvements in WPAI:SpA domains (8%–23%). Incremental PRO improvements were associated with improvement of activity impairment, presenteeism, and productivity loss. Relationships between absenteeism and PROs were the weakest, owing to absenteeism being low in the study population. Conclusion: Evidence of linear relationships between work productivity and activity impairment with patient‐reported pain, disease activity, and HRQoL was observed. Interventions to control pain and disease activity and improve HRQoL are therefore likely to improve work productivity and reduce activity impairment in patients with AS. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to explore to what extent patients with axial spondyloarthritis (axSpA) link experienced pain in the neck, back, and hips to inflammation and/or structural damage. Methods: Patients from the Groningen Leeuwarden Axial Spondyloarthritis (GLAS) cohort visiting the outpatient clinic between 2016 and 2019 filled out two additional questions in relation to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) question 2: (1) "To what extent do you think the pain you experience in your neck, back, and hips is related to inflammation caused by axSpA?" and (2) "To what extent do you think the pain you experience in your neck, back, and hips is related to damage of the spine and joints caused by axSpA?" Answers had to be depicted on a numeric rating scale from 0 (none) to 10 (very much); a difference of ≥2 points between the scores of these questions was considered clinically relevant in favor of the highest scoring question. Results: A total of 688 patients with axSpA (24% with nonradiographic axSpA [nr‐axSpA]) were included (62% male, mean ± SD age 48 ± 14 years, and mean ± SD Ankylosing Spondylitis Disease Activity Score [ASDAS] 2.3 ± 1.0). Seventy‐five percent of patients could not link the origin of their pain, 15% linked axial pain predominantly to inflammation, and 10% linked axial pain predominantly to damage. Patients in the inflammation group were younger, had shorter symptom duration, were more frequently diagnosed with nr‐axSpA, had higher ASDASCRP, had more often elevated CRP levels, had fewer comorbidities, had better spinal mobility, and had less spinal radiographic damage. Conclusion: In our large observational cohort, the majority of patients with axSpA could not differentiate the origin of experienced axial pain. If patients were able to link axial pain to clinical inflammation or damage, it was in concordance with clinical assessments and radiographic outcome, which may be helpful in establishing the origin of pain and supporting better patient‐centered treatment decisions. [ABSTRACT FROM AUTHOR]

Objective: The persistence of biologic (b) and targeted synthetic (ts) disease‐modifying antirheumatic drugs(DMARDs) in monotherapy versus in combination with conventional synthetic (cs) DMARDs is still a controversial topic in rheumatic diseases. To clarify this issue, the retention of the initial treatment strategy of b/tsDMARD in combination with csDMARD versus monotherapy in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) patients under real‐life conditions was evaluated. Factors associated with maintenance of the initial strategy were analysed. Methods: Nested cohort study within the Spanish BIOBADASER III registry. Bivariate comparisons and multivariate Cox proportional hazards models were used for the analyses. Results: A total of 2521 patients were included in the study. In the multivariate model, the initial strategy of combination therapy was associated with shorter persistence in patients with RA (hazard ratio [HR] 1.58;95% confidence interval [CI] 1.00–2.50; p =.049), PsA (HR 2.48; 95% CI 1.65–3.72) and AS (HR 16.77; 95% CI 7.37–38.16; p <.001), regardless of sex, time of disease progression, baseline disease activity, glucocorticoid use or type of b/tsDMARD. Overall, the combination strategy was associated with an increased incidence of adverse events (incidence rate ratio [IRR] 1.13; 95% CI 1.05–1.21). Conclusions: In this real‐life study, the strategy of combining a b/tsDMARD with a csDMARD is associated with lower persistence and worse safety profile compared to monotherapy in RA and especially in PsA and AS, suggesting that combination therapy should be rethought as first choice in RA patients, but especially in PsA and AS patients. [ABSTRACT FROM AUTHOR]

Upadacitinib is an orally administered, selective, Janus kinase inhibitor that is approved for several auto‐immune conditions, such as axial spondyloarthritis, an inflammatory rheumatic disease that includes ankylosing spondylitis (AS) and non‐radiographic axial spondyloarthritis (nr‐axSpA). The approvals of upadacitinib for the treatment of AS and nr‐axSpA were based on the safety and efficacy data for upadacitinib 15 mg once‐daily compared to placebo from the SELECT‐AXIS 1 and SELECT‐AXIS 2 studies. Population pharmacokinetic analyses based on data from 244 patients with axSpA showed that the pharmacokinetics of upadacitinib were comparable in subjects with AS and nr‐axSpA. Exposure‐response relationships were characterized for key efficacy and safety end points using data from 482 patients with axSpA. The exposure‐response analyses for efficacy based on Assessment of SpondyloArthritis International Society (ASAS)20 and ASAS40 responses at week 14, showed a clear differentiation from placebo with no evidence of increased responses with increasing upadacitinib plasma exposures. There were no clear exposure‐response trends observed for safety end points that included serious infections, herpes zoster, pneumonia, lymphopenia (grade ≥3), neutropenia (grade ≥3), or a greater than 2 g/dL decrease in hemoglobin from baseline through week 14. The exposure‐response analyses for efficacy and safety presented here supported the favorable benefit–risk profile with the use of upadacitinib 15 mg once‐daily for the treatment of axSpA. [ABSTRACT FROM AUTHOR]

Objective: We evaluated the incidence rate and factors associated with fractures among adults with ankylosing spondylitis (AS). Methods: We performed a retrospective cohort study with data from the Rheumatology Informatics System for Effectiveness registry linked to Medicare claims from 2016 to 2018. Patients were required to have two AS International Classification of Diseases codes 30 or more days apart and a subsequent Medicare claim. Then, 1 year of baseline characteristics were included, after which patients were observed for fractures. First, we calculated the incidence rate of fractures. Second, we constructed logistic regression models to identify factors associated with the fracture, including age, sex, race and ethnicity, body mass index, Medicare/Medicaid dual eligibility, area deprivation index, Charlson comorbidity index, smoking status, osteoporosis, historical fracture, and use of osteoporosis treatment, glucocorticoids, and opioids. Results: We identified 1,426 adults with prevalent AS. Mean ± SD age was 69.4 ± 9.8 years, 44.3% were female, and 77.3% were non‐Hispanic White. Fractures occurred in 197 adults with AS. The overall incidence rate of fractures was 76.7 (95% confidence interval [CI] 66.4–88.6) per 1,000 person‐years. Older age (odds ratio [OR] 2.8, 95% CI 1.39–5.65), historical fracture (OR 5.24, 95% CI 3.44–7.99), and use of more than 30 mg morphine equivalent (OR 1.86, 95% CI 1.08–3.19) conferred increased odds of fracture. Conclusions: In this large sample of Medicare beneficiaries with AS, increasing age, historical fracture, and use of opioids had higher odds of fracture. Men and women were equally likely to have a fracture. Because opioid use was associated with fracture in AS, this high‐risk population should be considered for interventions to mitigate risk. [ABSTRACT FROM AUTHOR]

Objective: The surgical treatment of patients with ankylosing spondylitis and severe thoracolumbar kyphosis combined with hip flexion contracture is very difficult for all the surgeons. The femoral neck osteotomy (FNO) is the first step to break the ice. The evaluation of a new modified FNO method is very important to improve the curative effect. Methods: Five male patients with nine bone‐fused hips who underwent the new femoral neck osteotomy were included from October 2021 to March 2022. The FNO was designed that the saw blade was manipulated from the lateral femoral neck base to the inferior part of the femoral head, keeping Pauwels' angle less than 30° on the coronal plane. On the transverse plane, the angle between the saw blade and the coronal plane was more than 15°. On the sagittal plane, the saw blade cut through the femoral neck. They accepted pedicle subtraction osteotomy (PSO) after FNO according to the patient' recovery. Then, 2 weeks later, the patients underwent total hip arthroplasty (THA). The visual analogue scale (VAS), Harris hip score (HHS) and passive hip flexion‐extension range of motion (ROM) were used to evaluate hip function. The data were analyzed by paired t‐test. Results: The average operation time and blood loss of FNO, the average interval between FNO and THA were collected. The average angle of the trunk and lower limb (ATL) was 36.33° ± 16.36° pre‐FNO, 82.89° ± 13.51° post‐FNO and 175.22° ± 3.42° post‐THA. The average VAS scores were 0 pre‐FNO, 5 ± 1.58 post‐FNO and 2.6 ± 0.55 post‐THA. The average HHS was 43.56 ± 1.59 preoperatively and 83.89 ± 2.21 postoperatively. The average hip extension ROM was 23.89° ± 12.69° pre‐FNO, −22.67° ± 14.18° post‐FNO and − 3.33° ± 2.50 post‐THA°. The average hip flexion ROM was 23.89° ± 12.69° pre‐FNO, 35.56° ± 12.11° post‐FNO and 104.44° ± 5.27° post‐THA. The differences among them were significant (p < 0.05). Only one hip (11.11%) displaced completely after FNO. Conclusion: A new modified FNO was developed, which can provide osteotomy with a certain degree of stability and greater ease for performing PSO and THA. [ABSTRACT FROM AUTHOR]

Aim: Ankylosing spondylitis (AS) is a chronic, progressive, and inflammatory autoimmune disease of unknown origin that affects the axial skeleton and sacroiliac joints, resulting in pain and loss of function. AS is characterized by the overdifferentiation of T helper 17 (Th17) cells, which contribute to the development of the disease. The Hippo signaling pathway is an important regulator of Th17 differentiation, but its role in patients with AS is unclear. We aimed to investigate the role of key molecules of the Hippo signaling pathway in inflammatory Th17 differentiation in patients with AS and to examine their correlation with disease stages. Methods: We examined the activity of the Hippo pathway in patients with AS and the regulation of Th17 differentiation during AS‐mediated inflammation. Blood samples were collected from 60 patients with AS at various stages and 30 healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood by density gradient centrifugation. The Serum Interleukin‐17 (IL‐17) levels in patients with AS and healthy controls were quantified by ELISA. The key molecules of Hippo pathway were assessed by real‐time PCR for their mRNA expression, and protein levels were determined by Western blot analysis. Results: Elevated serum interleukin‐17 (IL‐17) levels were observed in patients with AS compared with healthy controls. The protein and mRNA levels of retinoic acid receptor‐related orphan receptor γt (RORγt), transcriptional coactivator with a PDZ‐binding motif (TAZ), and key upstream transcription factors in the Hippo signaling pathway were measured. The expression of RORγt and TAZ was increased in the blood of patients with AS, whereas the expression of other Hippo pathway proteins, such as MST1/2 and NDR1/2, was significantly decreased. Increased levels of IL‐17 and TAZ were significantly associated with disease activity. In addition, MST1, MST2, and NDR1 levels were negatively correlated with TAZ, RORγt, and IL‐17 levels. Conclusion: Our findings suggest that the Hippo pathway plays a significant role in the regulation of Th17 differentiation and disease activity in patients with AS. The upregulation of TAZ and downregulation of key Hippo pathway proteins, such as MST1/2 and NDR1/2, may contribute to AS pathogenesis. These proteins may serve as biomarkers and may lead to the development of novel therapeutic strategies for AS. [ABSTRACT FROM AUTHOR]

Background: Claims‐based algorithms using International Classification of Diseases (ICD) codes have become a common approach for researchers to define ankylosing spondylitis (AS) in studies. To address potential misclassification bias caused by the claim‐based algorithms, we conducted the current study to validate whether these algorithms of medical claims could accurately represent AS diagnoses. Methods: Patients diagnosed with AS based on ICD codes were retrieved from the electronic medical records database at a Taiwanese medical center (Chung Shan University Hospital, Taiwan). After random sampling and stratification based on age and sex, the medical information of participants was appraised based on the 2009 ASAS guideline to evaluate the actual status of ICD codes claim‐based AS patients. Positive predict values (PPV) of different algorithms of ICD codes were also calculated. Results: Within the 4160 patients with claim‐based AS diagnosis, 387 eligible patients were finally included in the study design after random sampling. The PPV of the diagnostic algorithm of having at least 4 outpatient or 1 inpatient ICD record was 72.77 (95% CI, 66.79–78.75), whereas the PPV increased to 85.64 when the diagnoses were restricted to be made by rheumatologists (95% CI, 80.53–90.74). Conclusions: While performing database studies, researchers should be aware of the low PPV of specific algorithms when defining AS. Algorithms with higher PPV were recommended to be adopted to avoid misclassification biases. [ABSTRACT FROM AUTHOR]

This document provides an overview of the genetic factors, immune responses, and environmental influences involved in ankylosing spondylitis (AS), a rheumatic disorder. It discusses various genes and proteins that play a role in AS, including RANK, TNF-α, CTLA-4, Toll-like receptors, CARD8, Reelin, Calcium-Sensing Receptor, Anthrax Toxin Receptor 2, G protein-coupled receptors, epigenetic changes, and transcription factors. The document emphasizes the complexity of AS and the potential for targeted therapies and improved patient care through a deeper understanding of its genetic mechanisms. [Extracted from the article]

Magnetic resonance imaging (MRI) is a sensitive imaging modality to detect early inflammatory changes in axial spondyloarthritis (SpA). Over a decade has passed since the inclusion of MRI assessment in the 2009 Assessment of SpondyloArthritis International Society (ASAS) classification criteria for axial SpA. Evidence and clinical experience of MRI in axial SpA have accumulated rapidly since. This has led to a better understanding of the clinical utility of MRI in early diagnosis, disease activity assessment, and monitoring of treatment response in axial SpA. Furthermore, technological advancements have paved the way for the development of novel MRI sequences for the quantification of inflammation and image optimization. The field of artificial intelligence has also been explored to aid medical imaging interpretation, including MRI in axial SpA. This review serves to provide an update on the latest understanding of the evolving roles of MRI in axial SpA. [ABSTRACT FROM AUTHOR]

Objective: Ankylosing spondylitis is an insidiously progressive and debilitating form of arthritis involving the axial skeleton. MicroRNAs have been reported to act as candidate biomarkers for ankylosing spondylitis diagnosis and progression. The study aimed to assess the roles of circulating miR‐146a and miR‐155 in ankylosing spondylitis and their prediction to clinical response to TNF‐α blocking therapy. Methods: The study included 62 ankylosing spondylitis patients who were given originator TNFi with a 6‐month period. Responders to anti‐TNF treatment were defined as those reaching the Assessment of SpondyloArthritis international Society 40 (ASAS40) response at the 6‐month interval, and nonresponders were defined those not (n = 24). Results: The ankylosing spondylitis patients at M0 (before beginning TNFi treatment) had higher serum levels of miR‐146a and miR‐155 than the healthy controls (p <.0001). Lower serum levels of miR‐146a and miR‐155 were noted in the responders (n = 38) compared with the nonresponders (n = 24) at different time points after anti‐TNF treatment (p <.0001). The serum levels of miR‐146a and miR‐155 alone or in combination used to predict treatment outcomes produced AUCs of 0.884, 0.902, and 0.936, respectively. We submitted the following variables: miR‐146a and miR‐155 levels, BASDAI, ASDASCRP, ESR (mm/h), and CRP (mg/L) into multivariate logistic regression analysis, and results showed that higher levels of miR‐146a (OR: 13.75, 95%CI: 1.32 to 143.57, p =.029), miR‐155 (OR: 5.74, 95% CI: 1.63 to 20.20, p =.006), and ESR (OR: 1.08, 95% CI: 1.01 to 1.15, p =.022) were independent baseline predictors of ASAS40 response at 6‐month anti‐TNF‐a treatment. Conclusion: These findings obtained from the study suggest that high serum levels of miR‐146a and miR‐155 could aid in prediction of poor treatment outcomes after TNF‐α blocking therapy. [ABSTRACT FROM AUTHOR]

Rheumatic diseases, the immunosuppressant drugs used after solid organ transplantation to prevent graft rejection, and the biologics used for controlling rheumatic disease, especially tumor necrosis factor inhibitors (TNFi)—all of these could increase the risk of malignancy. The roles of biologics for disease control in rheumatic disease patients after kidney transplantation (KT) are not well established because only a few cases are reported, and the possibility of increasing infection and malignancy rates. Here, we present the first case of ankylosing spondylitis (AS) successfully treated with low‐dose TNFi for disease activity flare‐up 5 months after KT and review the literature to see whether the use of biologics, especially TNFi, in AS patients with disease activity flare‐ups after receiving KT is effective and safe. [ABSTRACT FROM AUTHOR]

Upadacitinib is a selective Janus kinase (JAK) inhibitor which is approved by the US Food and Drug Administration, the European Medicines Agency, as well as other agencies around the world for the treatment of several chronic inflammatory diseases, including rheumatic, dermatologic, and gastrointestinal diseases. Through inhibition of JAK, upadacitinib inhibits phosphorylation of downstream effector proteins, which consequently inhibits cytokine signaling for key pathways involved in inflammatory diseases. Upadacitinib more potently inhibits JAK1 than other JAK isoforms. The pharmacokinetics, pharmacodynamics, efficacy, and safety of upadacitinib were characterized in many clinical trials, which demonstrated the superiority of upadacitinib treatment over placebo or an active comparator in rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non‐radiographic axial spondyloarthritis, atopic dermatitis, Crohn's disease, and ulcerative colitis. The safety profile of upadacitinib supported a favorable benefit–risk profile across all the approved indications. In this article, we review the mechanism of action of upadacitinib and describe how the JAK–STAT (Janus kinase–signal transducers and activators of transcription) pathway is involved in the pathogenesis of several chronic and progressive immune‐mediated inflammatory diseases. In addition, this review also provides an overview of key clinical trials that were conducted as well as relevant data which supported the clinical development of upadacitinib and informed the recommended dose(s) in each of the approved indications. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the efficacy and safety of tofacitinib in patients with ankylosing spondylitis (AS) by prior biologic disease‐modifying antirheumatic drug (bDMARD) use. Methods: Data from a placebo‐controlled, double‐blind study of patients with active AS were analyzed. Patients received tofacitinib 5 mg twice daily (BID) or placebo to week 16; all received open‐label tofacitinib 5 mg BID to week 48 and were stratified by prior treatment (bDMARD‐naive or tumor necrosis factor inhibitor [TNFi]–inadequate responder [IR], including bDMARD‐experienced [non‐IR]). Disease activity/safety were assessed throughout. Results: Of 269 patients, 207 (77%) were bDMARD‐naive; 62 (23%) were in the TNFi‐IR subgroup. TNFi‐IR patients had higher baseline BMI (28.0 vs. 26.1 kg/m2), longer symptom duration (14.4 vs. 13.2 years), and lower concomitant conventional synthetic DMARD use (14.5% vs. 30.9%) than bDMARD‐naive patients. At week 16, for most outcomes, tofacitinib efficacy exceeded placebo for both subgroups and was sustained to week 48. At week 16, tofacitinib versus placebo differences were similar between bDMARD‐naive and TNFi‐IR patients (Assessment in Spondyloarthritis international Society 40 treatment difference [95% confidence interval]: 30.8% [19.1%‐42.6%] vs. 19.4% [1.7%‐37.0%]). Adverse event (AE) proportions were similar between tofacitinib‐treated bDMARD‐naive/TNFi‐IR patients (77.5%/77.4%) at week 48 with no deaths. A numerically higher proportion of tofacitinib‐treated TNFi‐IR versus bDMARD‐naive patients discontinued study drug (12.9% vs. 3.9%) or dose reduced/temporarily discontinued due to AEs (19.4% vs. 11.8%). Conclusion: Tofacitinib efficacy exceeded placebo at week 16 for bDMARD‐naive/TNFi‐IR patients and was sustained to week 48. The absolute magnitude of responses was generally greater in bDMARD‐naive patients versus TNFi‐IR patients. More TNFi‐IR versus bDMARD‐naive patients discontinued or dose reduced/temporarily discontinued tofacitinib due to AEs. Small sample size and sample size differences between subgroups limited the interpretation. [ABSTRACT FROM AUTHOR]