Unveiling the distinctive ossification patterns of diffuse idiopathic skeletal hyperostosis and ankylosing spondylitis using computed tomography three-dimensional reconstruction.

OBJECTIVE: To quantitatively analyze the morphological characteristics of osteophytes in DISH and syndesmophytes in AS, and summarize different ossification patterns to help identify the two diseases. Associated factors for new bone formation would be investigated. METHODS: Fifty patients with DISH and 50 age-, sex-, CT examination site- matched patients with AS were enrolled. Radiographic and clinical data were reviewed. Osteophytes (syndesmophytes) in front of each vertebral body and the corresponding intervertebral disc space were defined as vertebral osteophytes unit (VOU). The volume, angle and location (contralateral, ipsilateral, bilateral) of osteophytes in each VOU were measured and compared between DISH and AS groups. RESULTS: In each VOU, the volume and angle of osteophytes in DISH were significantly larger. The best osteophytes volume and angle cutoff value in predicting DISH was 0.59 cm3 and 40.15°. Contralateral, bilateral, ipsilateral osteophytes were recorded in 59.32%, 36.38%, 4.3% of assessed VOUs in patients with DISH and 64.78%, 29.31%, 5.91% in AS (p<0.001), respectively. As to ipsilateral osteophytes, the volume was inversely correlated with the center of the vertebral body to the center of the descending aorta (DISH: r = -0.45, p= 0.01; AS: r = -0.83, p<0.001). Advanced age, disease duration, smoking and overweight contribute to the progression of osteophytes and syndesmophytes. CONCLUSION: Morphological features of osteophytes are helpful to distinguish DISH with AS. Aortic pulsations inhibit or hinder new bone formation in both DISH and AS. Maintaining normal BMI could postpone osteophytes formation.

Bibliometric analysis of publications on enthesitis in spondyloarthritis in 2012-2021 based on web of science core collection databases.

Enthesitis, a characteristic of spondyloarthritis, has been paid considerable attention by researchers, and numerous enthesitis-related studies have been published in recent years. However, no study has been conducted to analyze enthesitis-related researches with bibliometric methods. This study aimed to provide a broad understanding of enthesitis-related researches and explore the direction of hot topics and future research trends from a bibliometric perspective. The global literatures on enthesitis published from 2012 to 2021 were scanned in the Web of Science Core Collection databases. Visualization and bibliometric analyses were generated by an online bibliometric platform and VOSviewer software to explore the hot topics and research trends. A total of 1,181 documents were included in this study. Publications were mainly from these countries in North America and Western Europe. Among these countries, the United States was the leading country with the maximum publication counts (210), highest h-index (47), and largest collaboration network as of June 29, 2022. The most influential journal and powerful author were Journal of Rheumatology and Professor Mease PJ, respectively. Co-occurrence analysis of keywords identified that "axial spondyloarthritis", "interleukin 23", and "secukinumab" might be the future hotspots. More and more attention had been paid to enthesitis in the past 10 years. Present studies focused on the effect of inflammatory cytokines involved in the pathogenesis and the development of antibodies against these factors. These studies played a key role in understanding the research direction and subsequent management of enthesitis, and helped researchers extract hidden valuable information for further study.

Symptoms compatible with Rome IV functional bowel disorder in patients with ankylosing spondylitis.

OBJECTIVES: To determine the frequency of symptoms meeting Rome IV functional bowel disorder (FBD) in patients with ankylosing spondylitis (AS), investigate factors associated with FBD symptoms, and assess whether having FBD symptoms might influence AS disease activity. METHODS: In this cross-sectional study, we enrolled 153 AS patients without known colonic ulcers and 56 sex- and age-matched controls to evaluate FBD (or its subtypes) symptoms. Disease characteristics were also evaluated in the AS group. RESULTS: Sixty (39.2%) of 153 AS patients had FBD symptoms, which were more prevalent than controls (23.2%). Besides, symptoms compatible with irritable bowel syndrome (IBS) and chronic diarrhoea were detected in 18 and 43 AS patients, respectively. For the AS group, multivariable logistic regression analyses showed that symptoms of FBD, IBS, and chronic diarrhoea were negatively associated with using non-steroidal anti-inflammatory drugs and positively associated with comorbid fibromyalgia, respectively. In exploration about the effects of FBD (or its subtypes) symptoms on AS disease activity by multivariable linear regression analyses, FBD symptoms and chronic diarrhoea had universal positive associations with assessments of AS disease characteristics, respectively. CONCLUSIONS: Patients with AS had frequent symptoms compatible with FBD, IBS, and chronic diarrhoea, proportions of which were lower in those with non-steroidal anti-inflammatory drug use. The improvement of FBD symptoms and chronic diarrhoea might be conducive to the disease status of AS patients.

[Review of Research Advances in Medical Service Robotics].

With the progress of science and technology and the increase of clinical demand, medical robots have developed rapidly and played a important role in promoting the medical cause. Service robot is a branch of medical robot, which is mainly oriented to medical service and assistance needs, and has been applied in many medical scenarios and achieved demonstration effects. This research first describes the development of medical service robots, and then summarizes the key technologies and clinical applications of robots. Finally, it points out the challenges and directions that medical service robots face at present, and puts forward prospects for their further development in the medical field.

Adherence, Efficacy, and Safety of Wearable Technology-Assisted Combined Home-Based Exercise in Chinese Patients With Ankylosing Spondylitis: Randomized Pilot Controlled Clinical Trial.

BACKGROUND: Clinical practice guidelines recommend that exercise is essential in the self-management of ankylosing spondylitis (AS). Attending supervised interventions requiring periodic medical center visits can be difficult and patients may decline participation, whereas effective home-based exercise interventions that do not require regular medical center visits are likely to be more accessible for AS patients. OBJECTIVE: The goal of the research was to investigate the adherence, efficacy, and safety of a wearable technology-assisted combined home-based exercise program in AS. METHODS: This was a 16-week investigator-initiated, assessor-blinded, randomized, pilot controlled trial conducted at Chinese People's Liberation Army General Hospital. We enrolled patients with AS who had no regular exercise habits and had been stable in drug treatment for the preceding month. Patients were randomly assigned (1:1) using a computer algorithm. An exercise program consisting of moderate-intensity aerobic exercise and functional exercise was given to the patients in the intervention group. The exercise intensity was controlled by a Mio FUSE Heart Rate Monitor wristband, which uses photoplethysmography to measure heart rate. Patients in the control group received usual care. The primary outcome was the difference in the Ankylosing Spondylitis Disease Activity Score (ASDAS). The secondary outcomes were patient global assessment (PGA), physician global assessment (PhGA), total pain, nocturnal pain, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), BAS Functional Index (BASFI), BAS Metrology Index (BASMI), Spondyloarthritis International Society Health Index (ASAS HI), 36-item Short Form Survey (SF-36), maximal oxygen uptake (VO2) max, body composition, range of motion of joints, and muscle endurance tests. Retention rate, adherence rate, barriers to being active, and adverse events were also assessed. RESULTS: A total of 77 patients were screened, of whom 55 (71%) patients were enrolled; 2% (1/55) withdrew without treatment after randomization. Patients were assigned to the intervention (n=26) or control group (n=28). The median adherence rate of the prescribed exercise protocol was 84.2% (IQR 48.7%-97.9%). For the primary outcome, between-group difference of ASDAS was significant, favoring the intervention (-0.2, 95% CI -0.4 to 0.02, P=.03). For the secondary outcomes, significant between-group differences at 16 weeks were detected in PGA, PhGA, total pain, BASDAI, BASDAI-fatigue, BASDAI-spinal pain, BASDAI-morning stiffness intensity, BASFI, and BASMI. Moreover, the frequency of difficulty in ASAS HI-motivation at 16 weeks was less in the intervention group (P=.03). Between-group difference for change from baseline were also detected in VO2 max, SF-36, back extensor endurance test, and the range of motion of cervical lateral flexion at 16 weeks. Lack of time, energy, and willpower were the most distinct barriers to being active. Incidences of adverse events were similar between groups (P=.11). CONCLUSIONS: Our pilot study suggests that this technology-assisted combined home-based exercise program can improve the clinical outcomes of patients with AS who have no exercise habit, with good adherence and safety profile. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900024244; http://www.chictr.org.cn/showproj.aspx?proj=40176.

Tai Chi exercise can ameliorate physical and mental health of patients with knee osteoarthritis: systematic review and meta-analysis.

OBJECTIVE: To systematically review the effects of Tai Chi exercise as a nonpharmacological therapeutic strategy on the physical and mental health in individuals with knee osteoarthritis. DATA SOURCES: A systematic literature retrieval has been conducted in PubMed, Web of Science, EMbase, CENTRAL, OVID, CINAHL, Physiotherapy Evidence Database, Chinese Biomedical Database and China National Knowledge Infrastructure up to June 2020 to identify the relevant randomised controlled trials (RCTs). METHODS: Two authors assessed independently the risk of bias using the Cochrane Collaboration's tool. Standardised mean difference (SMD) and 95% CI were calculated and data were combined using the fixed or random-effect model. The strength of evidence was rated with Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: A total of 16 RCTs involving 986 patients with knee osteoarthritis met the established inclusion criteria. The strength of evidence for the main outcomes was low or moderate. The systematic review illustrated the efficacy of Tai Chi exercise in treating and managing knee osteoarthritis. Patients' outcomes practising Tai Chi exercise were improved significantly, including pain (SMD = ‒0.69, 95%CI: ‒0.95 to ‒0.44, P < 0.001), stiffness (SMD = ‒0.59, 95%CI: ‒0.91 to ‒0.27, P < 0.001), physical function (SMD = ‒0.92, 95%CI: -1.16 to ‒0.69, P < 0.001), dynamic balance (SMD = 0.69, 95%CI: 0.38 to 0.99, P < 0.001), physiological and psychological health (SF-36 PCS: SMD = 0.48, 95%CI: 0.28 to 0.68, P < 0.001; SF-36 MCS: SMD = 0.26, 95%CI: 0.06 to 0.45, P = 0.01). No adverse events associated with Tai Chi exercise were reported. CONCLUSION: Tai Chi exercise was beneficial for ameliorating physical and mental health of patients with knee osteoarthritis and should be available as an alternative non-pharmacological therapy in rehabilitation programmes.

Add-On Effects of Conventional Synthetic Disease-Modifying Anti-Rheumatic Drugs in Ankylosing Spondylitis: Data from a Real-World Registered Study in China.

BACKGROUND The aim of this study was to investigate the effects of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) on patients with ankylosing spondylitis (AS) using real-world data, and to analyze patients' choices of csDMARDs and reasons for discontinuation. MATERIAL AND METHODS This observational study included 320 patients satisfying the modified New York criteria for AS. Patients were grouped according to medication: Group 1: 122 patients receiving non-steroidal anti-inflammatory drug (NSAID) monotherapy; Group 2: 198 patients receiving csDMARDs and NSAIDs. Patients were followed for 18 months at 6-month intervals. The change in AS Disease Activity Score and C-reactive protein (ASDAS-CRP) at each visit was the primary outcome. Secondary outcomes were based on validated disease activity questionnaires, clinical assessment, and acute-phase biomarkers (CRP and erythrocyte sedimentation rate [ESR]). Inter-group relationships were assessed across the 18-month follow-up period using generalized additive mixed models. RESULTS Sulfasalazine and thalidomide were the most commonly used csDMARDs, with cumulative use times of 8.9±4.1 months and 9.1±4.7 months, respectively. In Group 2, 56 patients discontinued or switched csDMARDs during the follow-up period, with lack of efficacy being the primary reason. The ASDAS-CRP was found to decrease significantly in both groups; however, improvements in many parameters (including ASDAS-CRP, disease activity questionnaires and ESR) were greater in Group 2. CONCLUSIONS Use of csDMARDs can improve disease activity in terms of ASDAS-CRP. The addition of csDMARDs may provide increased benefits compared with NSAID monotherapy, particularly in the reduction of AS disease activity, in the Chinese population.

"Mobile Health" for the Management of Spondyloarthritis and Its Application in China.

PURPOSE OF THE REVIEW: Spondyloarthritis (SpA) is a group of inflammatory diseases characterized by inflammation in the spine, peripheral joints, and entheses that usually start at the prime of one's life and lead to impaired physical function and reduced quality of life. Ankylosing spondylitis (AS) is prototype of SpA. This article reviews the opportunities and challenges of using mobile health (mHealth) in managing SpA, and report some of our experiences using a mHealth solution for management of SpA patients and performing related research in China. RECENT FINDINGS: The recent rapid development of mobile communications and the common use of intelligent electronic devices have led to the increasing application of mHealth for chronic disease management by healthcare providers and patients alike. This is a promising new technology that can help mitigate limitations in time and space for patient management, promote easier communication between patients and their healthcare providers, reduce medical expenses, and optimize medical services. We have developed a smartphone-based mHealth SpA management system (SpAMS) that also helps the patients to monitor, manage, and share information on their disease with their physician at regular intervals. There is a shift from a paternalistic model of healthcare to more personalized healthcare in which disease management is conducted by the patient together with their healthcare providers. The increasing utility of mHealth is expected to benefit disease management, promote patient-doctor communication, reduce medical expenses, and optimize medical services.

[A study on calculating the ankylosing spondylitis disease activity score according to the C-reactive protein level].

OBJECTIVE: To study the prediction value of C-reactive protein (CRP) level to ankylosing spondylitis disease activity score (ASDAS), the most widely used activity score in ankylosing spondylitis (AS). METHODS: A total of 386 patients with AS were enrolled and divided into 2 groups by CRP ≥ 3.5 mg/L (n=266) and CRP<3.5 mg/L(n=120). ASDAS-CRP was evaluated in patients with CRP below the normal range (3.5 mg/L) in different subgroups. Three methods were used to test the consistency between ASDAS-CRP and ASDAS-erythrocyte sedimentation rate (ESR). RESULTS: The ASDAS-CRP showed a good correlation with the ASDAS-ESR when CRP level was ≥ 3.5 mg/L (r=0.899, P=0.000). In the group of CRP <3.5 mg/L, ASDAS-ESR showed better consistency with ASDAS-CRP when CRP level was below 1.5 mg/L(intra-class correlation coefficient 0.902; kappa coefficient 0.70). By the evaluation of variant gradient matrix, CRP 1.5 mg/L coincided with disease activity states. CONCLUSION: There is good consistency between ASDAS-CRP and ASDAS-ESR. When CRP level is below the normal range, 1.5 mg/L could be a cut-off value to calculate the optimal ASDAS-CRP score.

Non-Pharmacological Strategies for Managing Sarcopenia in Chronic Diseases.

This article focuses on a range of non-pharmacological strategies for managing sarcopenia in chronic diseases, including exercise, dietary supplements, traditional Chinese exercise, intestinal microecology, and rehabilitation therapies for individuals with limited limb movement. By analyzing multiple studies, the article aims to summarize the available evidence to manage sarcopenia in individuals with chronic diseases. The results strongly emphasize the role of resistance training in addressing chronic diseases and secondary sarcopenia. Maintaining the appropriate frequency and intensity of resistance training can help prevent muscle atrophy and effectively reduce inflammation. Although aerobic exercise has limited ability to improve skeletal muscle mass, it does have some positive effects on physical function. Building upon this, the article explores the potential benefits of combined training approaches, highlighting their helpfulness for overall quality of life. Additionally, the article also highlights the importance of dietary supplements in combating muscle atrophy in chronic diseases. It focuses on the importance of protein intake, supplements rich in essential amino acids and omega-3, as well as sufficient vitamin D to prevent muscle atrophy. Combining exercise with dietary supplements appears to be an effective strategy for preventing sarcopenia, although the optimal dosage and type of supplement remain unclear. Furthermore, the article explores the potential benefits of intestinal microecology in sarcopenia. Probiotics, prebiotics, and bacterial products are suggested as new treatment options for sarcopenia. Additionally, emerging therapies such as whole body vibration training, blood flow restriction, and electrical stimulation show promise in treating sarcopenia with limited limb movement. Overall, this article provides valuable insights into non-pharmacological strategies for managing sarcopenia in individuals with chronic diseases. It emphasizes the importance of a holistic and integrated approach that incorporates exercise, nutrition, and multidisciplinary interventions, which have the potential to promote health in the elderly population. Future research should prioritize high-quality randomized controlled trials and utilize wearable devices, smartphone applications, and other advanced surveillance methods to investigate the most effective intervention strategies for sarcopenia associated with different chronic diseases.

The prevalence of sarcopenia in spondyloarthritis patients: a meta-analysis.

BACKGROUND: Spondyloarthritis (SpA) is a chronic inflammatory disorder that affects sacroiliac joints and spine, resulting in substantial disability. Sarcopenia, characterized by the loss of muscle mass and function, is a prevalent comorbidity in various chronic diseases. However, the exact prevalence of sarcopenia in SpA patients remains uncertain. The objective of this study is to conduct a systematic review and meta-analysis of the available literature to determine the prevalence of sarcopenia in SpA. METHODS: A comprehensive search was conducted in EMBASE, MEDLINE, WEB OF SCIENCE, and COCHRANE databases to identify relevant studies published up to 2023. Studies investigating the prevalence of sarcopenia in SpA patients were included. Data on study characteristics, participant demographics, diagnostic criteria for sarcopenia, and prevalence rates were extracted. Meta-analysis was performed using a random-effects model to estimate the overall prevalence of sarcopenia in SpA patients. RESULTS: A total of 16 studies that met the inclusion criteria were included in the systematic review. These studies encompassed a combined sample size of 999 patients with SpA. The meta-analysis findings revealed that the overall prevalence of sarcopenia in SpA patients was 25.0% (95% confidence interval: 0.127 to 0.352). Furthermore, the prevalence of presarcopenia and severe sarcopenia was found to be 21.0% and 8.7%, respectively. Subgroup analysis was conducted to examine different diagnostic criteria, subtypes, and sex of SpA in relation to sarcopenia. CONCLUSION: This systematic review and meta-analysis provide a comprehensive overview of the prevalence of sarcopenia in SpA patients. The findings suggest a high prevalence of sarcopenia in SpA patients, emphasizing the need for targeted interventions to prevent and manage sarcopenia. And further research is needed to explore the underlying mechanisms and potential therapeutic strategies for sarcopenia in SpA.

Assessing and Optimizing Large Language Models on Spondyloarthritis Multi-Choice Question Answering: Protocol for Enhancement and Assessment.

BACKGROUND: Spondyloarthritis (SpA), a chronic inflammatory disorder, predominantly impacts the sacroiliac joints and spine, significantly escalating the risk of disability. SpA's complexity, as evidenced by its diverse clinical presentations and symptoms that often mimic other diseases, presents substantial challenges in its accurate diagnosis and differentiation. This complexity becomes even more pronounced in nonspecialist health care environments due to limited resources, resulting in delayed referrals, increased misdiagnosis rates, and exacerbated disability outcomes for patients with SpA. The emergence of large language models (LLMs) in medical diagnostics introduces a revolutionary potential to overcome these diagnostic hurdles. Despite recent advancements in artificial intelligence and LLMs demonstrating effectiveness in diagnosing and treating various diseases, their application in SpA remains underdeveloped. Currently, there is a notable absence of SpA-specific LLMs and an established benchmark for assessing the performance of such models in this particular field. OBJECTIVE: Our objective is to develop a foundational medical model, creating a comprehensive evaluation benchmark tailored to the essential medical knowledge of SpA and its unique diagnostic and treatment protocols. The model, post-pretraining, will be subject to further enhancement through supervised fine-tuning. It is projected to significantly aid physicians in SpA diagnosis and treatment, especially in settings with limited access to specialized care. Furthermore, this initiative is poised to promote early and accurate SpA detection at the primary care level, thereby diminishing the risks associated with delayed or incorrect diagnoses. METHODS: A rigorous benchmark, comprising 222 meticulously formulated multiple-choice questions on SpA, will be established and developed. These questions will be extensively revised to ensure their suitability for accurately evaluating LLMs' performance in real-world diagnostic and therapeutic scenarios. Our methodology involves selecting and refining top foundational models using public data sets. The best-performing model in our benchmark will undergo further training. Subsequently, more than 80,000 real-world inpatient and outpatient cases from hospitals will enhance LLM training, incorporating techniques such as supervised fine-tuning and low-rank adaptation. We will rigorously assess the models' generated responses for accuracy and evaluate their reasoning processes using the metrics of fluency, relevance, completeness, and medical proficiency. RESULTS: Development of the model is progressing, with significant enhancements anticipated by early 2024. The benchmark, along with the results of evaluations, is expected to be released in the second quarter of 2024. CONCLUSIONS: Our trained model aims to capitalize on the capabilities of LLMs in analyzing complex clinical data, thereby enabling precise detection, diagnosis, and treatment of SpA. This innovation is anticipated to play a vital role in diminishing the disabilities arising from delayed or incorrect SpA diagnoses. By promoting this model across diverse health care settings, we anticipate a significant improvement in SpA management, culminating in enhanced patient outcomes and a reduced overall burden of the disease. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/57001.

Dietary Fiber Intake Influences Changes in Ankylosing Spondylitis Disease Status.

The objectives of this study were to characterize dietary fiber (DF) intake in patients with ankylosing spondylitis (AS), to assess whether DF intake affects disease activity in AS, and to investigate the effect of DF intake on disease activity in AS in the context of functional bowel disease (FBD) symptoms. We recruited 165 patients with AS and divided them into two groups according to whether they had a high DF intake > 25 g/d to investigate the characteristics of people with high DF intake. Some 72 of the 165 AS patients (43%) met the criteria for high DF intake, which was more common in patients with negative FBD symptoms (68%). Data analysis revealed that DF intake was negatively associated with AS disease activity and did not differ statistically significantly from FBD symptoms. Multivariate adjusted models were used to explore the effect of DF intake on AS disease activity. ASDAS-CRP and BASDAI were stable and negatively correlated across models in both groups with and without FBD symptoms. Thus, DF intake positively affected disease activity in patients with AS. ASDAS-CRP and BASDAI were negatively correlated with DF intake.

Cigarette Smoking Increases the Prevalence of Hip Joint Involvement in Ankylosing Spondylitis: A Real-World Case-Control Study.

OBJECTIVE: To investigate the association between cigarette smoking and hip joint involvement in ankylosing spondylitis (AS). METHODS: This case-control study compared patients with AS with and without hip involvement, as defined by the Bath Ankylosing Spondylitis Radiology Hip Index. Logistic regression analysis, subgroup analysis, and sensitivity analysis were conducted to estimate the association between smoking and hip involvement in AS. RESULTS: This study included 103 patients with hip involvement (cases) and 89 patients without hip involvement (controls). In univariate analysis, patients who had juvenile-onset AS (JAS), were younger, were male, had peripheral arthritis history, or had cigarette exposure were prone to hip involvement. After adjusting for confounding factors, JAS (adjusted odds ratio [aOR] 2.52, 95% CI 1.26-5.06), male sex (aOR 2.89, 95% CI 1.14-7.33), and cigarette smoking (aOR 7.23, 95% CI 2.27-23.05) were regarded to be independently associated with hip involvement in AS. Moreover, patients who smoked with exposure of less than 10 pack-years were 2.2 times more likely to have hip involvement than those without (aOR 2.21, 95% CI 1.09-4.47). This association was reproduced in subgroup analyses of males and propensity score-matched subjects, and it withstood sensitivity analysis. CONCLUSION: Smoking is a novel independent risk factor for hip involvement in AS; even exposure of less than 10 pack-years could contribute to increased prevalence of hip involvement in AS, which underlines the significance of smoking cessation in patients with AS, especially for JAS.

Results of flow cytometric detection of gamma-deltaT cells in peripheral blood of patients with ankylosing spondylitis: a pilot study.

Previous studies have suggested that gamma-delta T cells play an important role in the pathogenesis of ankylosing spondylitis (AS). In this pilot study, the peripheral blood mononuclear cells (PBMCs) of patients with ankylosing spondylitis (AS) and healthy volunteers were stained and analyzed by flow cytometry to distinguish gamma-delta T cells and its subtypes, and then to report the distribution of gamma-delta T cells and iyts subtypes and their correlation with ankylosing spondylitis. A total of 17 patients with active AS and 10 age- and gender- matched healthy volunteers were enrolled in this study, and their peripheral blood were drawn to collect mononuclear cells (PBMCs). Flow cytometry was used to analyze gamma-delta T cell subpopulations by measuring the surface and intracellular expressions of phenotypic markers. Serum levels of inflammatory and bone turnover markers were measured, and their correlations with subpopulations of gamma-delta T cells were evaluated. In patients with AS, the Vdelta2 fractions within gamma-delta T cells and CD3+ T cells decreased significantly, in particular, the proportions of CD27+ Vdelta2 T cells, CD86+CD80+ Vdelta1 T cells, and IL17A-secreting and TNFalpha-secreting Vdelta1 T cells within the parental cells decreased significantly. gamma-delta T cells/PBMCs, Vdelta2 cells/gamma-delta T cells, and Vdelta2 cells/CD3+ T cells were negatively correlated with CRP, whereas Vdelta1 cells/CD3+ T cells were negatively correlated with ESR. Vdelta1 cells/gamma-delta T cells were positively correlated with CRP, gamma-deltaT cells/PBMCs were positively correlated with beta-CTx, CD69+CD25+ and IL-17A-secreting Vdelta1 cells were positively correlated with TP1NP, and CD69+CD25+ Vdelta1 and Vdelta2 cells were positively correlated with osteocalcin. Decreases in peripheral Vdelta2, CD27+ Vdelta2, CD86+CD80+ Vdelta1, and IL17A or TNFalpha-secreting Vdelta1 T cells are associated with AS. The correlations between gamma-delta T cell subpopulations and CRP and the CD69+CD25+ subpopulation with TP1NP or osteocalcin suggest that an imbalance in peripheral gamma-delta T cell subpopulations contributes to the pathogenesis of AS.

Clinical value of plasmablasts in predicting disease relapse in patients with IgG4-related disease.

OBJECTIVES: To explore the value of plasmablasts in predicting disease relapse in IgG4-related diseases (IgG4-RD). METHODS: Treatment-naïve IgG4-RD patients treated with glucocorticoid (GC) monotherapy or leflunomide (LEF) and GC combination therapy diagnosed at the Chinese PLA General Hospital during February 2017 and January 2018 were included in this study. The absolute plasmablast count was measured by using the absolute count tubes with flow cytometry. Patients were categorized into high and low plasmablast level groups by defining the median number of plasmablasts as the cut-off value. The characteristics of the clinical manifestations between the two groups were compared. In addition, the correlation of plasmablast count with other indicators and its clinical value in predicting disease relapse were evaluated. RESULTS: Data of 37 treatment-naïve IgG4-RD patients were analyzed. The median (IQR) absolute count of plasmablasts was 4.0 (2.8-7.5)/µL, which was correlated with the lymphocyte percentage, serum IgG, IgG4, and IgG4/IgG. The baseline absolute count of plasmablasts was an independent risk factor for disease relapse in IgG4-RD patients (HR, 1.199; 95% CI, 1.030-1.396, P = 0.019), and the application of LEF was an independent protective factor (HR, 0.283; 95% CI, 0.106-0.759, p = 0.012). CONCLUSIONS: The present study preliminarily indicated that baseline absolute plasmablast count may independently predict disease relapse in patients with IgG4-RD treated with GC monotherapy or LEF and GC combination therapy. More efforts are still needed to be performed in the future. Key Points • The absolute count of plasmablasts is correlated with the lymphocyte percentage, serum IgG, IgG4 and IgG4/IgG. • The baseline absolute plasmablast count may predict disease relapse in patients with IgG4-RD treated with GC monotherapy or LEF and GC combination therapy. • The application of LEF is an independent protective factor for disease relapse in IgG4-RD.

Risk of infections of biological and targeted drugs in patients with spondyloarthritis: meta-analysis of randomized clinical trials.

BACKGROUND: Concerns exist regarding the risk of infections in patients with spondyloarthritis (SpA) treated with biologics. We assessed the risk of infections of biological and targeted drugs in patients with SpA by performing a meta-analysis based on randomized controlled trials (RCTs). METHODS: A systematic literature search was conducted in PubMed, Embase, Web of Science, the Cochrane Library, and China Biology Medicine Disc for RCTs evaluating the risk of infections of biological therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto odds ratio (OR) for infections in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using the Cochrane Risk of Bias Tool. RESULTS: In total, 62 studies were included in this meta-analysis. Overall, the risk of infection (Peto OR: 1.16, 95% confidence interval [CI]: 1.07-1.26, P < 0.001), serious infection (Peto OR: 1.65, 95% CI: 1.26-2.17, P < 0.001), upper respiratory tract infection (URTI) (Peto OR: 1.17, 95% CI: 1.04-1.32, P = 0.008), nasopharyngitis (Peto OR: 1.25, 95% CI: 1.10-1.42, P < 0.001), and Candida infection (Peto OR: 2.64, 95% CI: 1.48-4.71, P  = 0.001) were increased in SpA patients treated with biologics compared with placebo. Sensitivity analysis based on biologics classes was conducted, and results demonstrated that compared with placebo, there was a higher risk of infection for tumor necrosis factor (TNF)-a inhibitors (Peto OR: 1.38, 95% CI: 1.13-1.68, P  = 0.001) and interleukin (IL)-17 inhibitors (Peto OR: 1.55, 95% CI: 1.08-2.22, P  = 0.018) in axial SpA, and for Janus kinase inhibitors in peripheral SpA (Peto OR: 1.39, 95% CI: 1.14-1.69, P  = 0.001); higher risk of serious infection for IL-17 inhibitors in peripheral SpA (Peto OR: 3.46, 95% CI: 1.26-9.55, P = 0.016) and axial SpA (Peto OR: 2.01, 95% CI: 1.38-2.91, P < 0.001); higher risk of URTI for TNF-a inhibitors in axial SpA (Peto OR: 1.37, 95% CI: 1.05-1.78, P = 0.019), and for apremilast in peripheral SpA (Peto OR: 1.60, 95% CI: 1.08-2.36, P = 0.018); higher risk of nasopharyngitis for TNF-a inhibitors in axial SpA (Peto OR: 1.41, 95% CI: 1.05-1.90, P = 0.022) and peripheral SpA (Peto OR: 1.49, 95% CI: 1.09-2.05, P = 0.013), and for IL-17 inhibitors in axial SpA (Peto OR: 1.35, 95% CI: 1.01-1.82, P = 0.044); higher risk of herpes zoster for Janus kinase inhibitors in peripheral SpA (Peto OR: 2.18, 95% CI: 1.03-4.62, P = 0.043); higher risk of Candida infection for IL-17 inhibitors in peripheral SpA (Peto OR: 2.52, 95% CI: 1.31-4.84, P = 0.006). CONCLUSIONS: This meta-analysis shows that biological therapy in patients with SpA may increase the risk of infections, including serious infections, URTI, nasopharyngitis, and Candida infection, which should be paid attention to in our clinical practice.

Risk of tuberculosis in patients with rheumatoid arthritis treated with biological and targeted drugs: meta-analysis of randomized clinical trials.

BACKGROUND: Concerns exist regarding the potential development of tuberculosis in patients with rheumatoid arthritis (RA) treated with biological and targeted drugs. We assessed systematically whether biological therapy increased the risk of tuberculosis in patients with RA by meta-analysis of randomized controlled trials (RCTs). METHODS: A systematic literature search was conducted in PubMed, Embase, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating biological therapy in patients with RA from inception through August 2021. Traditional meta-analysis and network meta-analysis were performed to compare the risk of tuberculosis for each biologics class in patients with RA. Peto odds ratio (Peto OR) and its 95% confidence interval (CI) were calculated as the primary effect measure. RESULTS: In total, 39 studies with 20,354 patients were included in this meta-analysis, and 82 patients developed tuberculosis. The risk of tuberculosis was increased in patients treated with biologics compared with non-biologics (Peto OR: 3.86, 95% CI: 2.36-6.32, P < 0.001). Also, tumor necrosis factor-α (TNF-α) inhibitors had a higher probability of developing tuberculosis than placebo (Peto OR: 3.98, 95% CI: 2.30-6.88, P < 0.001). However, network meta-analysis demonstrated that there was no significant difference in the risk of tuberculosis for each biologics class in patients with RA. Noticeably, tuberculosis was significantly more common in patients treated with a high dose compared with patients receiving a low dose of tofacitinib (Peto OR: 7.39, 95% CI: 2.00-27.31, P = 0.003). CONCLUSION: This meta-analysis demonstrates the evidence of an elevated risk of tuberculosis in patients with RA treated with TNF-α inhibitors, and a dose-dependent elevated risk of tuberculosis in patients treated with tofacitinib.

Risk of Malignancy and Tuberculosis of Biological and Targeted Drug in Patients With Spondyloarthritis: Systematic Review and Meta-analysis of Randomized Controlled Trials.

Objective: Concerns exist regarding the potential development of malignancy and tuberculosis in patients with spondyloarthritis (SpA) treated with biologics. We assessed the extent to which biologic therapy may increase the risk of malignancy and tuberculosis in patients with SpA by meta-analysis to derive estimates of sparse harmful events occurring in Randomized Controlled Trials (RCTs). Methods: A systematic literature search was conducted in PubMed, EMbase, Web of Science, the Cochrane Library, and China Biology Medicine disc for RCTs evaluating the risk of sparse harmful events of biologic therapy in patients with SpA from inception through August 9, 2021. We calculated a pooled Peto OR for malignancy and tuberculosis in biologics-treated patients vs. placebo patients. The risk of bias on the included RCTs was assessed by using Cochrane Risk of Bias tool. Results: In total, 63 studies were included in this meta-analysis, and 83 patients and 7 patients developed malignancy and tuberculosis, respectively. Overall, the risk of malignancy and tuberculosis was increased in SpA patients treated with biologics compared to placebo (malignancy: Peto OR: 2.49, 95%CI: 1.61-3.87, p < 0.001; tuberculosis: Peto OR: 5.98, 95%CI: 1.29-27.76, p = 0.022). Remarkably, compared to placebo, there was higher risk of malignancy for IL-17 inhibitors (Peto OR: 3.68, 95%CI: 1.20-11.30, p = 0.023) and small molecule targeted drugs (Peto OR: 3.08, 95%CI: 1.37-6.90, p = 0.043) in peripheral SpA, and for TNF receptor-Fc fusion protein in axial SpA (Peto OR: 7.18, 95%CI: 1.21-42.69, p = 0.030). Besides, the risk of tuberculosis was higher for anti-TNFα antibody in axial SpA (Peto OR: 6.17, 95%CI: 1.03-37.13, p = 0.046). Conclusion: This meta-analysis showed an elevated risk of malignancy in patients with peripheral SpA treated with biologics, especially for IL-17 inhibitors, and small molecule targeted drugs, a slightly increased risk of malignancy in TNF receptor-Fc fusion protein in axial SpA, and increased risk of tuberculosis in patients with axial SpA treated with anti-TNFα antibody. These findings need to be validated by studies with larger population and longer follow-up.

Underweight and obesity are strong predictors of clinical outcomes in patients with ankylosing spondylitis: data from the Smart-phone SpondyloArthritis Management System.

BACKGROUND: The aim of this study was to examine the impact of underweight, overweight and obesity on clinical outcomes and treatment responses to biologics in Chinese patients with ankylosing spondylitis (AS). METHODS: Body mass index (BMI) was available in 1074 patients from the Smart-phone SpondyloArthritis Management System. Patients were categorized into four groups based on BMI: underweight, normal weight, overweight and obesity. Multivariable median regression analyses examined the effect of underweight and obesity on clinical outcomes and treatment response to biologics. RESULTS: Among 1074 patients with AS, normal weight accounted for 49.1%, while underweight, overweight, and obesity for 8.1%, 30.1%, and 12.0%, respectively. Compared to patients with normal weight, patients with underweight, overweight and obesity had an increased disease activity, while patients with underweight and obesity had a significantly poor Bath Ankylosing Spondylitis Functional Index and Assessment of Spondyloarthritis International Society Health Index scores. For tumor necrosis factor (TNF)-α inhibitor users, BMI was found to be negatively correlated with changes in disease activity in the multivariate regression model (all p < 0.05). Besides, the patients using TNF-α inhibitor in the overweight or obesity categories were much less likely to achieve a significant reduction on disease activity during follow-up period in the multivariate regression model (all p < 0.05), taking these with normal-weight patients as a reference. CONCLUSIONS: Both underweight and obesity except for overweight were associated independently with worse disease activity, physical function and health status. Overweight and obesity might impact on treatment responses to biologics in patients with AS. This argues that weight management, to maintain it at a normal level, should be one of the disease management strategies in patients with AS.