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OBJECTIVE: To phenotype SLE based on symptom burden (disease damage, system involvement and patient reported outcomes), with a specific focus on objective and subjective cognitive function. METHODS: SLE patients ages 18-65 years underwent objective cognitive assessment using the ACR Neuropsychological Battery (ACR-NB) and data were collected on demographic and clinical variables, disease burden/activity, health-related quality of life (HRQoL), depression, anxiety, fatigue and perceived cognitive deficits. Similarity network fusion (SNF) was used to identify patient subtypes. Differences between the subtypes were evaluated using Kruskal-Wallis and χ2 tests. RESULTS: Of the 238 patients, 90% were female, with a mean age of 41 years (s.d. 12) and a disease duration of 14 years (s.d. 10) at the study visit. The SNF analysis defined two subtypes (A and B) with distinct patterns in objective and subjective cognitive function, disease burden/damage, HRQoL, anxiety and depression. Subtype A performed worst on all significantly different tests of objective cognitive function (P

ObjectiveWe previously demonstrated the utility of the Automated Neuropsychological Assessment Metrics (ANAM) for screening cognitive impairment (CI) in patients with systemic lupus erythematosus (SLE) and developed composite indices for interpreting ANAM results. Our objectives here were to provide further support for the ANAM's concurrent criterion validity against the American College of Rheumatology neuropsychological battery (ACR-NB), identify the most discriminatory subtests and scores of the ANAM for predicting CI, and provide a new approach to interpret ANAM results using Classification and Regression Tree (CART) analysis.Methods300 adult SLE patients completed an adapted ACR-NB and ANAM on the same day. As per objectives, six models were built using combinations of ANAM subtests and scores and submitted to CART analysis. Area under the curve (AUC) was calculated to evaluate the ANAM's criterion validity compared to the adapted ACR-NB; the most discriminatory ANAM subtests and scores in each model were selected, and performance of models with the highest AUCs were compared to our previous composite indices; decision trees were generated for models with the highest AUCs.ResultsTwo models had excellent AUCs of 86 and 89%. Eight most discriminatory ANAM subtests and scores were identified. Both models demonstrated higher AUCs against our previous composite indices. An adapted decision tree was created to simplify the interpretation of ANAM results.ConclusionWe provide further validity evidence for the ANAM as a valid CI screening tool in SLE. The decision tree improves interpretation of ANAM results, enhancing clinical utility.

BackgroundThe evaluation of Patient Reported Outcomes Measurement Information System (PROMIS) computerized adaptive test (CAT) in adults with systemic lupus erythematous (SLE) is an emerging field of research. We aimed to examine the test-retest reliability and construct validity of the PROMIS CAT in a Canadian cohort of patients with SLE.MethodsTwo hundred twenty-seven patients completed 14 domains of PROMIS CAT and seven legacy instruments during their clinical visits. Test-retest reliability of PROMIS was evaluated 7-10 days from baseline using intraclass correlation coefficient (ICC (2; 1)). The construct validity of the PROMIS CAT domains was evaluated against the commonly used legacy instruments, and also in comparison to disease activity and disease damage using Spearman correlations. A multitrait-multimethod matrix (MMM) approach was used to further assess construct validity comparing selected 10 domains of PROMIS and SF-36 domains.ResultsModerate to excellent reliability was found for all domains (ICC [2;1] ranging from lowest, 0.66 for Sleep Disturbance and highest, 0.93 for the Mobility domain). Comparing seven legacy instruments with 14 domains of PROMIS CAT, moderate to strong correlations (0.51-0.91) were identified. The average time to complete all PROMIS CAT domains was 11.7 min. The MMM further established construct validity by showing moderate to strong correlations (0.55-0.87) between select PROMIS and SF-36 domains; the average correlations from similar traits (convergent validity) were significantly greater than the average correlations from different traits.ConclusionsThese results provide evidence on the reliability and validity of PROMIS CAT in SLE in a Canadian cohort.

ObjectiveCognitive function may change over time in patients with systemic lupus erythematosus (SLE), and cognitive function trajectories have not been well studied. We aimed to identify cognitive function trajectories in SLE and describe them with depressive symptoms trajectories, and we also aimed to identify baseline factors associated with class membership in the dual trajectories.MethodsLongitudinal data from the University of California San Francisco Lupus Outcomes Study were analyzed. Two outcome trajectories were studied jointly, the Hopkins Verbal Learning Test-Revised and the Center for Epidemiologic Studies Depression Scale (CES-D) (administered annually). Univariate/multivariable logistic regression analyses examined baseline factors associated with class memberships.ResultsA total of 755 patients were studied, and 4 latent classes were identified: 1) low CES-D scores and low cognitive scores (no depression plus cognitive impairment; 20%), 2) lowest CES-D scores and highest normal cognitive scores (no depression plus normal cognition; 48%), 3) highest CES-D scores and lowest cognitive scores (depression plus cognitive impairment; 9%), and 4) high CES-D scores and cognitive score at borderline (depression plus borderline cognition; 23%).ConclusionIn all, 4 distinct classes of dual cognitive function and depressive symptoms were identified. Persistently low cognitive performance in 28% of patients (classes 1 and 3) did not significantly improve over 7 years. Cognitive impairment was associated with depression status in 9% of patients (class 3). Other factors also predicted latent class membership: ethnicity, education, disease activity, physical functioning, and bodily pain. These results highlight the importance of periodic assessment of cognitive function and of different aspects relevant for assessing and managing cognitive function over time in SLE.

Microneedles (MNs), renowned for their painless and minimally invasive qualities, exhibit significant potential for facilitating effective drug delivery, vaccination, and targeted sample extraction. Extracellular vesicles (EVs), serving as cargo for MNs, are naturally occurring nanovesicles secreted by cells and characterized by novel biomarkers, low immunogenicity, and cell-source-specific traits. MNs prove instrumental in extracting EVs from the sample fluid, thereby facilitating a promising diagnostic and prognostic tool. To harness the therapeutic potential of EVs in tissue repair, MNs with sustained delivery of EVs leverage micron-sized channels to enhance targeted site concentration, demonstrating efficacy in treating various diseases, such as Achillea tendinopathy, hair loss, spinal cord injury, and diabetic ulcers. EV-loaded MNs emerge as a promising platform for repair applications of skin, cardiac, tendon, hair, and spinal cord tissues. This review commences with an overview of MNs, subsequently delving into the role of EVs as cargo for MNs. The paper then synthesizes the latest advancements in the use of EV-loaded MNs for tissue regenerative repair, extending to research progress in extracting EVs from MNs for disease diagnosis and prognostic evaluations. It aims to offer valuable insights and forecast future research trajectories with the hope of inspiring innovative ideas among researchers in this field. [ABSTRACT FROM AUTHOR]

Objectives Cognitive dysfunction (CD) is a common manifestation of SLE that can have detrimental consequences for those affected. To date, no treatments have been approved for SLE-CD. This study aims to assess the association of azathioprine (AZA) and mycophenolate (MMF) use with SLE-CD, given that these medications have demonstrated neuroprotective qualities in prior studies. Methods Consecutive adult SLE patients presenting to a single healthcare center were considered for participation. The ACR neuropsychological battery for SLE was administered to consenting patients at 0, 6 and 12 months. Scores were compared with age- and sex-matched controls. Primary outcome was CD, defined as a z -score ≤−1.5 in two or more cognitive domains. Mixed-effects logistic regression models were constructed to estimate the odds of CD with respect to AZA and MMF use. Results A total of 300 participants representing 676 patient visits completed the study; 114 (38%) met criteria for CD at baseline. The cumulative AZA dose (g/kg) was associated with reduced odds of CD [odds ratio (OR) 0.76 (95% CI 0.58, 0.98), P  = 0.04]. Years of AZA treatment was also associated with reduced odds of CD [OR 0.72 (95% CI 0.54, 0.97), P  = 0.03]. MMF use was not associated with CD. Conclusion AZA use was associated with significantly lower odds of SLE-CD, while MMF use was not. Additional studies are warranted to further investigate the relationship of AZA and SLE-CD. [ABSTRACT FROM AUTHOR]

Objectives The objectives of this study were to determine the trajectories of depressive symptoms in patients with SLE and to identify baseline characteristics that are associated with a patient's trajectory of depression. Methods Data from the Lupus Outcomes Study at the University of California, San Francisco were analysed. Depressive symptomatology was assessed in years two through seven using the Center for Epidemiologic Studies Depression Scale (CES-D), with higher scores representing more severe depressive symptoms. Group-based trajectory modelling was used to determine latent classes of CES-D scores over time. Ordinal logistic regression analyses were performed to identify baseline characteristics associated with worse classes of depressive symptoms. Results CES-D scores for 763 individuals with SLE over 6 years were mapped into four distinct classes. Class 1 (36%) and class 2 (32%) comprised the largest proportion of the cohort and were defined by the lowest and low CES-D scores (no depression), respectively. Class 3 (22%) and class 4 (10%) had high and the highest scores (depression), respectively. Greater age [odds ratio (OR): 0.97, 95% CI: 0.96, 0.99] and higher education level (OR: 0.79, 95% CI: 0.70, 0.89) at baseline were associated with lower odds of membership in worse classes of depressive symptoms. Conversely, lower income (OR: 1.73, 95% CI: 1.03, 2.92), worse SF-36 physical functioning scores (OR: 1.12, 95% CI: 1.12, 1.13) and worse SF-36 bodily pain scores (OR: 1.58, 95% CI: 1.55, 1.61) were positively associated with membership in worse classes of depressive symptoms. Conclusion Four classes of depressive symptoms were identified in patients with SLE. Understanding the trajectories of depressive symptoms and the associated risk factors can aid in the management of these symptoms in individuals living with SLE. [ABSTRACT FROM AUTHOR]