Exploring complement biomarkers in suspected axial spondyloarthritis.

OBJECTIVES: To investigate lectin pathway proteins (LPPs) as biomarkers for axial spondyloarthritis (axSpA) in a cross-sectional cohort with a suspicion of axSpA, comprising newly diagnosed axSpA and chronic low back pain (cLBP) individuals. METHODS: Serum samples from 515 participants within the OptiRef cohort, including 151 axSpA patients and 364 cLBP patients, were measured using immunoassays for LPPs (mannan-binding lectin (MBL), collectin liver-1 (CL-L1), M-ficolin, H-ficolin and L-ficolin, MBL-associated serine proteases (MASP)-1, -2 and -3, MBL-associated proteins (MAp19 and MAp44) and the complement activation product C3dg). RESULTS: Serum levels of L-ficolin, MASP-2 and C3dg were elevated in axSpA patients, whereas levels of MASP-3 and CL-L1 were decreased, and this remained significant for C3dg and MASP-3 after adjustment for C reactive protein (CRP). A univariate regression analysis showed serum levels of CL-L1, MASP-2, MASP-3 and C3dg to predict the diagnosis of axSpA, and MASP-3 and C3dg remained significant in a multivariate logistic regression analysis. Assessment of the diagnostic potential showed that a combination of human leukocyte antigen B27 (HLA-B27) and measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, however, with a concomitant loss of sensitivity. CONCLUSIONS: Serum levels of complement activation, that is, C3dg, and MASP-3 differed significantly between axSpA and cLBP patients after adjustment for CRP. Although combining HLA-B27 with measurements of L-ficolin, MASP-3 and C3dg increased the diagnostic specificity for axSpA, this seems unjustified due to the concomitant loss of sensitivity. However, both C3dg and MASP-3 were associated with axSpA diagnosis in multivariate logistic regression, suggesting an involvement of complement in the inflammatory processes and possibly pathogenesis in axSpA.

Impact of body composition on clinical outcomes in patients with active radiographic axial spondyloarthritis under biological therapy.

OBJECTIVE: To assess the association of body composition, evaluated by bioimpedance analysis (BIA), with disease activity, physical function, and mobility in patients with axSpA undergoing bDMARD treatment for one year. METHODS: Patients with AS (radiographic axSpA) were enrolled in an extension of the German Spondyloarthritis Inception Cohort (GESPIC). Patients were required to be candidates for bDMARD therapy at baseline presenting high disease activity despite previous treatment with nonsteroidal anti-inflammatory drugs. Outcomes (disease activity, function, and mobility) and body composition parameters were assessed at baseline and every 6 months thereafter. Body composition was assessed by BIA. The association between body composition parameters and outcomes over 1 year was analyzed using longitudinal generalized estimating equations. RESULTS: Seventy-four patients with radiographic axSpA were included in current analysis with a mean age of 36.5 years, disease duration of 6.2 years and ASDAS-CRP score of 3.4 at baseline. Fat mass value and fat mass index were positively associated with disease activity (ASDAS: ß = 0.01, 95% CI [-0.01, 0.03] and ß = 0.04, 95% CI [-0.01, 0.08], respectively) and functional disability (BASFI). Visceral adipose tissue (VAT) was associated with reduced spine mobility (BASMI: ß = 0.20, 95% CI [0.07, 0.33]). Additionally, increase in VAT and fat mass parameters was linked to worse disease activity and functional disability in women, while they were strongly associated with reduced spinal mobility in men. CONCLUSIONS: Higher levels of body fat and VAT were positively associated with increased disease activity, functional disability, and reduced spinal mobility in patients with radiographic axSpA treated with bDMARDs.

Comparison of the effect of treatment with NSAIDs added to anti-TNF therapy versus anti-TNF therapy alone on the progression of structural damage in the spine over 2 years in patients with radiographic axial spondyloarthritis from the randomised-controlled CONSUL trial.

OBJECTIVES: The study aimed to evaluate the effect of adding a non-steroidal anti-inflammatory drug (NSAID), celecoxib (CEL), to a tumour necrosis factor inhibitor (TNFi), golimumab (GOL), compared with TNFi monotherapy on radiographic spinal progression in patients with radiographic axial spondyloarthritis (r-axSpA) over 2 years. METHODS: R-axSpA patients, having risk factors for radiographic progression (high disease activity plus C reactive protein >5 mg/L and/or ≥1 syndesmophyte(s)), underwent a 12-week run-in phase with GOL 50 mg every 4 weeks. In the core phase (96 weeks), only patients with a good clinical response at week 12 were randomised (1:1) to GOL+CEL 200 mg two times per day (combination therapy) or GOL monotherapy. The primary endpoint was radiographic progression assessed by modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS) change at week 108 in the intent-to-treat population. RESULTS: A total of 128 patients were enrolled in the run-in phase; and 109 patients were randomised at week 12 to monotherapy (n=55) or combination therapy (n=54). At week 108, 97 (52 vs 45) patients completed the study. The change in mSASSS at week 108 was 1.7 (95% CI 0.8 to 2.6) in the monotherapy vs 1.1 (95% CI 0.4 to 1.8) in the combination therapy groups (p=0.79). New syndesmophytes occurred in 25% of patients in the monotherapy vs 11% of patients in the combination therapy groups (p=0.12). During the study, no significant differences in adverse events and serious adverse events were observed between the groups. CONCLUSIONS: Combination therapy with GOL+CEL did not demonstrate statistically significant superiority over GOL monotherapy in retarding radiographic spinal progression over 2 years in r-axSpA.

Deep Learning Detects Changes Indicative of Axial Spondyloarthritis at MRI of Sacroiliac Joints.

Background MRI is frequently used for early diagnosis of axial spondyloarthritis (axSpA). However, evaluation is time-consuming and requires profound expertise because noninflammatory degenerative changes can mimic axSpA, and early signs may therefore be missed. Deep neural networks could function as assistance for axSpA detection. Purpose To create a deep neural network to detect MRI changes in sacroiliac joints indicative of axSpA. Materials and Methods This retrospective multicenter study included MRI examinations of five cohorts of patients with clinical suspicion of axSpA collected at university and community hospitals between January 2006 and September 2020. Data from four cohorts were used as the training set, and data from one cohort as the external test set. Each MRI examination in the training and test sets was scored by six and seven raters, respectively, for inflammatory changes (bone marrow edema, enthesitis) and structural changes (erosions, sclerosis). A deep learning tool to detect changes indicative of axSpA was developed. First, a neural network to homogenize the images, then a classification network were trained. Performance was evaluated with use of area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. P < .05 was considered indicative of statistically significant difference. Results Overall, 593 patients (mean age, 37 years ± 11 [SD]; 302 women) were studied. Inflammatory and structural changes were found in 197 of 477 patients (41%) and 244 of 477 (51%), respectively, in the training set and 25 of 116 patients (22%) and 26 of 116 (22%) in the test set. The AUCs were 0.94 (95% CI: 0.84, 0.97) for all inflammatory changes, 0.88 (95% CI: 0.80, 0.95) for inflammatory changes fulfilling the Assessment of SpondyloArthritis international Society definition, and 0.89 (95% CI: 0.81, 0.96) for structural changes indicative of axSpA. Sensitivity and specificity on the external test set were 22 of 25 patients (88%) and 65 of 91 patients (71%), respectively, for inflammatory changes and 22 of 26 patients (85%) and 70 of 90 patients (78%) for structural changes. Conclusion Deep neural networks can detect inflammatory or structural changes to the sacroiliac joint indicative of axial spondyloarthritis at MRI. © RSNA, 2022 Online supplemental material is available for this article.

Diagnosing axial spondyloarthritis: estimation of the disease probability in patients with a priori different likelihoods of the diagnosis.

OBJECTIVE: To evaluate the diagnostic value of SpA parameters and their combination for the diagnosis of axial SpA in patients with an a priori different probability of the diagnosis. METHODS: A total of 361 patients with chronic back pain and suspicion of axial SpA (181 referred by primary care physicians or orthopaedists, 180 recruited via an online screening tool) received a structured rheumatologic examination, which resulted into a diagnosis or exclusion of axial SpA. The prevalence of axial SpA indicating the pre-test probability was 40% in the physician-referred subgroup and 20% in the online screening subgroup. Sensitivities, specificities and likelihood ratios for SpA features were determined in both subgroups and the respective post-test probabilities of axial SpA were calculated. RESULTS: The relative diagnostic value of single SpA features varied substantially between the groups with different referral pathways. For instance, HLA-B27 positivity increased the probability of the presence of axial SpA by 35% to 55% in online-screened patients and by 22% to 62% in physician-referred patients. The absence of HLA-B27 resulted in a sharp decrease in the probability of the presence of axial SpA in physician-referred patients (from 40% to 6%). This decrease was less sharp in the online screening group (from 20% to 10%). These differences were especially relevant in patients with a small number (one to two) of positive SpA features. CONCLUSION: The diagnostic value of SpA features varies in different patient populations, which should be considered in the diagnostic approach.

Comparison of an online self-referral tool with a physician-based referral strategy for early recognition of patients with a high probability of axial spa.

OBJECTIVES: The diagnostic delay in axial spondyloarthritis (axial SpA) remains unacceptably high, with one of the reasons being a late referral. Structured physician-based referral programs are able to improve early diagnosis, but lack of implementation is still an issue. The objective of this study was to evaluate an online self-referral (OSR) tool for patients with back pain and to compare it to an established physician-based referral tool. METHODS: Patients with back pain were included if they either fulfilled the requirements of the OSR tool or were referred by a physician using the Berlin referral tool. Rheumatologists in the specialized center performed a structured assessment in all patients that resulted in the final diagnosis of axial SpA / no axial SpA. Furthermore, we attempted to optimize the OSR tool in terms of maximizing the specificity constrained by a sensitivity of at least 90% of the original strategy. RESULTS: 361 consecutive patients (180 via the OSR and 181 via the Berlin referral tool) were included in the study. A total of 35 patients (19.4%) in the self-referral group and 71 patients (39.2%) in the physician-referral group were finally diagnosed with axial SpA. Axial SpA patients from the OSR group were more often HLA-B27 negative, females, and were more frequently at a non-radiographic stage as compared to axial SpA patients who came via the physician-based tool. Both groups had, however, a similar disease burden. According to the pre-defined selection criterion we identified an optimized combination of ≥2 IBP parameters and ≥1 other SpA parameters (in addition to both stem parameters). CONCLUSIONS: Despite the better performance of the physician-based referral strategy, the proportion of axial SpA among self-referred patients (19.4%) was clearly higher than the assumed 5% prevalence of axial SpA in patients with chronic back pain. Based on our data driven approach the performance of the OSR strategy could be further improved if at least two IBP parameters plus one additional SpA parameter had to be present in addition to the stem parameters. The OSR tool can be used in specialized centers in addition to a physician-based referral strategy to improve early diagnosis and to increase awareness of axial SpA.

Sexual Coercion in the College Population: A Form of Risk-Taking Behavior.

The purpose of this study was to examine whether a decision-making model of risk-taking behavior, specifically impulsivity, positive and negative outcome expectation, and sensation seeking, can be extended to motivation for perpetration of sexual coercion. Participants included 276 sexually active college students between the ages of 18 and 25 years old who completed a set of questionnaires: (a) Sexual Experiences Survey, (b) Sensation Seeking Scales, (c) Cognitive Appraisal of Risky Events, (d) Barratt Impulsiveness Scale, and (e) Reckless Behavior Questionnaire. Multiple regression analyses were utilized to examine the relationship between these decision-making models and sexually coercive behaviors. General risk-taking behaviors were positively correlated with acts of sexual coercion, r = .16, p < .01. The predictor variables accounted for a significant amount of the variance in sexual coercion, R2 = .11, F(4, 246) = 7.57, p < .01. Only sensation seeking contributed unique variance to our model of sexual coercion, ß = .27, t = 4.06, p < .01. Interventions to reduce sexual coercion may be more successful if they target those high in risk-taking. Similarly, prevention efforts informed by research on how to engage and hold the attention of sensation seeking youth may be more successful.

Performance of the Ankylosing Spondylitis Disease Activity Score based on a quick quantitative C-reactive protein assay in patients with axial spondyloarthritis.

OBJECTIVES: To evaluate the performance of the Ankylosing Spondylitis Disease Activity Score based on a validated quick quantitative C-reactive protein assay (ASDAS-qCRP) as compared to ASDAS based on a routine lab CRP assay (ASDAS-CRP) and ASDAS based on erythrocyte sedimentation rate (ASDAS-ESR). METHODS: Disease activity assessment was performed in 50 patients with axial spondyloarthritis (axSpA). Routine lab CRP was measured in the central lab while the quantitative quick-CRP assay and ESR measurements were performed locally. ASDAS-CRP, ASDAS-qCRP and ASDAS-ESR were subsequently calculated. RESULTS: The mean (±SD) serum level of the routine lab CRP (6.2±8.3mg/l) was lower than of the quick-CRP (7.4±8.4mg/l) (P<0.05). Whereat, there was no significant difference in the mean values of ASDAS-CRP and ASDAS-qCRP in axSpA patients (2.70±0.94 and 2.74±0.96, respectively, P=0.069), while the ASDAS-ESR (2.85±1.0) was significantly higher than ASDAS-CRP (P=0.036) and numerically higher than ASDAS-qCRP (P=0.125). In 47 of the 50 cases of axSpA (94%), patients were assigned to the same disease activity category according to ASDAS-CRP and ASDAS-qCRP. CONCLUSIONS: ASDAS-qCRP performed similarly well compared to ASDAS-CRP with the absolute agreement on the disease activity category according to the ASDAS of 94%. ASDAS-qCRP is, therefore, feasible for an immediate decision-making in clinical practice and trials aimed at treating to target.

Online Mate-Retention Tactics on Facebook Are Associated With Relationship Aggression.

A measure of Facebook-related mate-retention tactics was developed to investigate the relationship between online behaviors and intimate partner aggression. One hundred and seventy-seven young adults (65 men, 112 women) completed questionnaires that included measures of online and offline mate-retention tactics, Facebook jealousy, Facebook surveillance, and intimate partner violence. A factor analysis yielded four subscales for the Facebook Mate-Retention Tactic Inventory (FMRTI): Care and Affection, Jealousy and Surveillance, Possession Signals, and Punishment of Infidelity Threat. The FMRTI total scores were positively correlated with Facebook jealousy, Facebook surveillance, and use of offline mate-retention tactics. The Jealousy and Surveillance subscale uniquely predicted intimate partner psychological and physical aggression over and above existing measures. Facebook mate-retention tactics fully mediated the relation between Facebook jealousy and both intimate partner psychological and physical aggression. The current study provides preliminary evidence for conceptualizing Facebook as an environment for the use of mate-retention tactics that have real-life implications for intimate partner violence.

Physically Abused Women's Experiences of Sexual Victimization and their Children's Disruptive Behavior Problems.

OBJECTIVE: Despite the substantial co-occurrence of women's experiences of physical and sexual violence, very little is known about their separate and combined effects on child functioning. The present study examines whether sexual victimization experienced by physically abused women is associated with their children's disruptive behavior problems, after controlling for mothers' physical victimization and parent to child aggression. It also tests the hypothesis that maternal distress mediates the association between women's sexual victimization and their children's disruptive behavior problems. METHOD: The sample includes 449 mothers and their children (4-8 years) who were recruited while residing in domestic violence shelters. Mothers reported on their experiences of physical and sexual victimization over the past year and their current symptoms of psychological distress. Trained diagnosticians interviewed mothers about their children's disruptive behavior problems. RESULTS: Approximately 75% of the women reported experiences of sexual victimization. Physically abused women's experiences of sexual victimization correlated positively with their children's disruptive behavior problems and their own psychological distress. The results of path analyses indicated that maternal psychological distress mediates the relation between women's experiences of sexual victimization and their children's disruptive behavior problems. CONCLUSIONS: This research suggests that physically abused women's experiences of sexual victimization are important for understanding their children's disruptive behavior problems. Additionally, this research provides further evidence that maternal psychological distress is important for understanding how intimate partner violence might influence children.

Improving parenting in families referred for child maltreatment: a randomized controlled trial examining effects of Project Support.

Project Support is an intervention designed to decrease coercive patterns of aggressive discipline and increase positive parenting. This research evaluates Project Support in a sample of families reported to Children's Protective Services (CPS) for allegations of physical abuse or neglect; 35 families with a child between 3- and 8-years-old participated. In all families, CPS allowed the children to remain in the family home while the family received services. Families were randomly assigned to receive either Project Support or services as usual, which were provided by CPS or CPS-contracted service providers. To evaluate intervention effects, a multimethod, multi-informant assessment strategy was used that included data from mothers' reports, direct observation of parents' behavior, and review of CPS records for re-referrals for child maltreatment. Families who received Project Support services showed greater decreases than families who received services as usual in the following areas: mothers' perceived inability to manage childrearing responsibilities, mothers' reports of harsh parenting, and observations of ineffective parenting practices. Only 5.9% of families in the Project Support condition had a subsequent referral to CPS for child maltreatment, compared with 27.7% of families in the comparison condition. The results suggest that Project Support may be a promising intervention for reducing child maltreatment among families in which it has occurred.