Schroeder Arthritis Institute

COVID-19 shares the feature of autoantibody production with systemic autoimmune diseases. In order to understand the role of these immune globulins in the pathogenesis of the disease, it is important to explore the autoantibody spectra. Here we show, by a cross-sectional study of 246 individuals, that autoantibodies targeting G protein-coupled receptors (GPCR) and RAS-related molecules associate with the clinical severity of COVID-19. Patients with moderate and severe disease are characterized by higher autoantibody levels than healthy controls and those with mild COVID-19 disease. Among the anti-GPCR autoantibodies, machine learning classification identifies the chemokine receptor CXCR3 and the RAS-related molecule AGTR1 as targets for antibodies with the strongest association to disease severity. Besides antibody levels, autoantibody network signatures are also changing in patients with intermediate or high disease severity. Although our current and previous studies identify anti-GPCR antibodies as natural components of human biology, their production is deregulated in COVID-19 and their level and pattern alterations might predict COVID-19 disease severity.

OBJECTIVE: Osteoarthritis (OA) is a complex disease involving contributions from both local joint tissues and systemic sources. Patient characteristics, encompassing sociodemographic and clinical variables, are intricately linked with OA rendering its understanding challenging. Technological advancements have allowed for a comprehensive analysis of transcripts, proteomes and metabolomes in OA tissues/fluids through omic analyses. The objective of this review is to highlight the advancements achieved by omic studies in enhancing our understanding of OA pathogenesis over the last three decades. DESIGN: We conducted an extensive literature search focusing on transcriptomics, proteomics and metabolomics within the context of OA. Specifically, we explore how these technologies have identified individual transcripts, proteins, and metabolites, as well as distinctive endotype signatures from various body tissues or fluids of OA patients, including insights at the single-cell level, to advance our understanding of this highly complex disease. RESULTS: Omic studies reveal the description of numerous individual molecules and molecular patterns within OA-associated tissues and fluids. This includes the identification of specific cell (sub)types and associated pathways that contribute to disease mechanisms. However, there remains a necessity to further advance these technologies to delineate the spatial organization of cellular subtypes and molecular patterns within OA-afflicted tissues. CONCLUSIONS: Leveraging a multi-omics approach that integrates datasets from diverse molecular detection technologies, combined with patients' clinical and sociodemographic features, and molecular and regulatory networks, holds promise for identifying unique patient endophenotypes. This holistic approach can illuminate the heterogeneity among OA patients and, in turn, facilitate the development of tailored therapeutic interventions.

Statistics Canada estimated that approximately 1.4 million Canadians suffer from long COVID. Although cardiovascular changes during acute SARS-CoV-2 infection are well documented, long-term cardiovascular sequelae are less understood. In this review, we sought to characterize adult cardiovascular outcomes in the months after acute COVID-19 illness. In our search we identified reports of outcomes including cardiac dysautonomia, myocarditis, ischemic injuries, and ventricular dysfunction. Even in patients without overt cardiac outcomes, subclinical changes have been observed. Cardiovascular sequelae after SARS-CoV-2 infection can stem from exacerbation of preexisting conditions, ongoing inflammation, or as a result of damage that occurred during acute infection. For example, myocardial fibrosis has been reported months after hospital admission for COVID-19 illness, and might be a consequence of myocarditis and myocardial injury during acute disease. In turn, myocardial fibrosis can contribute to further outcomes including dysrhythmias and heart failure. Severity of acute infection might be a risk factor for long-term cardiovascular consequences, however, cardiovascular changes have also been reported in young, healthy individuals who had asymptomatic or mild acute disease. Although evolving evidence suggests that previous SARS-CoV-2 infection might be a risk factor for cardiovascular disease, there is heterogeneity in existing evidence, and some studies are marred by measured and unmeasured confounders. Many investigations have also been limited by relatively short follow-up. Future studies should focus on longer term outcomes (beyond 1 year) and identifying the prevalence of outcomes in different populations on the basis of acute and long COVID disease severity.

Fungal infections represent a major global health problem affecting over a billion people that kills more than 1.5 million annually. In this study, we employed an integrative approach to reveal the landscape of the human immune responses to Candida spp. through meta-analysis of microarray, bulk, and single-cell RNA sequencing (scRNA-seq) data for the blood transcriptome. We identified across these different studies a consistent interconnected network interplay of signaling molecules involved in both Toll-like receptor (TLR) and interferon (IFN) signaling cascades that is activated in response to different Candida species (C. albicans, C. auris, C. glabrata, C. parapsilosis, and C. tropicalis). Among these molecules are several types I IFN, indicating an overlap with antiviral immune responses. scRNA-seq data confirmed that genes commonly identified by the three transcriptomic methods show cell type-specific expression patterns in various innate and adaptive immune cells. These findings shed new light on the anti-Candida immune response, providing putative molecular pathways for therapeutic intervention.

Pathway Data Integration Portal (PathDIP) is an integrated pathway database that was developed to increase functional gene annotation coverage and reduce bias in pathway enrichment analysis. PathDIP 5 provides multiple improvements to enable more interpretable analysis: users can perform enrichment analysis using all sources, separate sources or by combining specific pathway subsets; they can select the types of sources to use or the types of pathways for the analysis, reducing the number of resulting generic pathways or pathways not related to users' research question; users can use API. All pathways have been mapped to seven representative types. The results of pathway enrichment can be summarized through knowledge-based pathway consolidation. All curated pathways were mapped to 53 pathway ontology-based categories. In addition to genes, pathDIP 5 now includes metabolites. We updated existing databases, included two new sources, PathBank and MetabolicAtlas, and removed outdated databases. We enable users to analyse their results using Drugst.One, where a drug-gene network is created using only the user's genes in a specific pathway. Interpreting the results of any analysis is now improved by multiple charts on all the results pages. PathDIP 5 is freely available at https://ophid.utoronto.ca/pathDIP.

In recent decades, the development of new drugs has become increasingly expensive and inefficient, and the molecular mechanisms of most pharmaceuticals remain poorly understood. In response, computational systems and network medicine tools have emerged to identify potential drug repurposing candidates. However, these tools often require complex installation and lack intuitive visual network mining capabilities. To tackle these challenges, we introduce Drugst.One, a platform that assists specialized computational medicine tools in becoming user-friendly, web-based utilities for drug repurposing. With just three lines of code, Drugst.One turns any systems biology software into an interactive web tool for modeling and analyzing complex protein-drug-disease networks. Demonstrating its broad adaptability, Drugst.One has been successfully integrated with 21 computational systems medicine tools. Available at https://drugst.one, Drugst.One has significant potential for streamlining the drug discovery process, allowing researchers to focus on essential aspects of pharmaceutical treatment research.

INTRODUCTION: We investigated the prevalence of new or persistent manifestations experienced by COVID-19 survivors at 3 or more months after their initial infection, collectively known as post-COVID-19 condition (PCC). METHODS: We searched four electronic databases and major grey literature resources for prospective studies, systematic reviews, authoritative reports and population surveys. A random-effects meta-analysis pooled the prevalence data of 22 symptoms and outcomes. The GRADE approach was used to assess the certainty of evidence. PROSPERO CRD42021231476. RESULTS: Of 20 731 identified references, 194 met our inclusion criteria. These studies followed 483 531 individuals with confirmed COVID-19 diagnosis over periods of up to 2 years. Most focused on adults, nearly two-thirds were conducted in Europe and 63% were of high or moderate quality. The supplementary search identified 17 systematic reviews, five authoritative reports and four population surveys that reported on PCC prevalence. Our analysis revealed that more than half of COVID-19 survivors experienced one or more symptoms more than a year after their initial infection. The most common symptoms were fatiguedyspneamemory, sleep or concentration disturbances; depressionand pain. Limitation in returning to work was the most common outcome. Prevalence tended to be higher among females, individuals hospitalized during their initial infection and those who experienced severe COVID-19 illness. CONCLUSION: PCC presents a significant health burden, affecting some groups more than others. This information will help inform health care system policies and services for people living with PCC and those caring for them.

Several perturbations in the number of peripheral blood leukocytes, such as neutrophilia and lymphopenia associated with Coronavirus disease 2019 (COVID-19) severity, point to systemic molecular cell cycle alterations during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, the landscape of cell cycle alterations in COVID-19 remains primarily unexplored. Here, we performed an integrative systems immunology analysis of publicly available proteome and transcriptome data to characterize global changes in the cell cycle signature of COVID-19 patients. We found significantly enriched cell cycle-associated gene co-expression modules and an interconnected network of cell cycle-associated differentially expressed proteins (DEPs) and genes (DEGs) by integrating the molecular data of 1469 individuals (981 SARS-CoV-2 infected patients and 488 controls [either healthy controls or individuals with other respiratory illnesses]). Among these DEPs and DEGs are several cyclins, cell division cycles, cyclin-dependent kinases, and mini-chromosome maintenance proteins. COVID-19 patients partially shared the expression pattern of some cell cycle-associated genes with other respiratory illnesses but exhibited some specific differential features. Notably, the cell cycle signature predominated in the patients' blood leukocytes (B, T, and natural killer cells) and was associated with COVID-19 severity and disease trajectories. These results provide a unique global understanding of distinct alterations in cell cycle-associated molecules in COVID-19 patients, suggesting new putative pathways for therapeutic intervention.

Immunoglobulins play a fundamental role in the protection of the human body against internal and external threats. They also contribute to the immune system homeostasis and maintenance of self-tolerance. Hypogammaglobulinemia is occasionally encountered in routine clinical practice by rheumatologists. Low levels of immunoglobulins can occur as primary or secondary issues and may predispose patients to various forms of infection. However, the impact of the low immunoglobulin level abnormality varies with the underlying condition. In this narrative review, we shed light on the overall types and functions of immunoglobulins for clinicians. We discuss important principles of immunoglobulin measurements. We then consider the primary and secondary causes of low immunoglobulins with a special focus on hypogammaglobulinemia in patients with systemic lupus erythematosus (SLE).

Abstract Objective In the absence of axial psoriatic arthritis (axPsA)-specific tools, the BASDAI and Ankylosing Spondylitis Disease Activity Score (ASDAS) are used to assess axial symptoms in patients with PsA. Here, we assessed the performance of BASDAI and ASDAS in patients with PsA. Methods Patients with active PsA in DISCOVER-1 and DISCOVER-2 (ClinicalTrials.gov: NCT03162796 and NCT03158285, respectively) with or without axPsA but with available baseline BASDAI information were analysed; those with investigator-identified axial symptoms and imaging-confirmed sacroiliitis comprised the axPsA cohort. Correlations between BASDAI/ASDAS and clinical variables were assessed with Pearson’s coefficient (r). Longitudinal effects of enthesitis (Leeds Enthesitis Index [LEI]), swollen joint count and presence versus absence of axPsA on BASDAI/ASDAS (normalized 0–10 scale) were analysed with mixed models for repeated measures. Results At baseline in the axPsA (n = 312) and non-axPsA (n = 124) cohorts, BASDAI scores showed no or weak correlation with swollen joint count (0.18–0.20), tender joint count (0.12–0.29), LEI (–0.04 to 0.24) and physician global assessment (0.35–0.43); moderate correlation with fatigue (both −0.56); and strong correlation with patient global assessment of disease activity (0.62–0.69) and patient-reported pain (0.66–0.70). Similar correlations were observed for ASDAS. Axial involvement versus non-involvement was associated with higher BASDAI scores and ASDAS (all β ≥ 0.5), without differences between instruments; longitudinal associations between swollen joint count (β ≤ 0.06)/LEI (β ≤ 0.19) and BASDAI/ASDAS were clinically unimportant. Conclusion BASDAI and ASDAS performed similarly in patients with active PsA and axial involvement, independent of peripheral disease involvement, supporting their performance in assessing axial disease activity. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT03162796 and NCT03158285.

OBJECTIVES: Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease in which a significant proportion of patients remain refractory to existing therapies. The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) initiated a project aimed at unravelling the reasons for treatment failures in PsA, culminating in the establishment of definitions for difficult-to-treat PsA (D2T-PsA) and complex-to-manage PsA (C2M-PsA). This study explores patient perspectives on treatment-resistant PsA, incorporating a broader patient perspective into the overarching GRAPPA project. METHODS: A multilingual (10 languages), online survey to explore PsA patients' perspectives on treatment inefficacies was used. It was developed collaboratively by GRAPPA members and patient research partners. It included sections on demographic data, structured questions about treatment failures, and open-ended questions. Data analysis used descriptive statistics and inductive coding of qualitative responses via Dedoose. RESULTS: Among 570 respondents, most were female (68.8%) and White (72.6%), with an average PsA diagnosis delay of 4.3 years. Key contributors to D2T- and C2M-PsA were persistent joint pain and psoriasis (65.7%), fatigue (52.8%) and medication side effects (41.7%). Ranked by impact, arthritis was the most debilitating symptom. Quality of life concerns were notable, with sleep impairment and reduced life enjoyment being reported by 66.4%. Language differences emerged; for instance, Dutch and Italian respondents prioritized fatigue and daily life impact, respectively. CONCLUSION: This is the first international study to highlight patient-driven insights in the management of resistant PsA, emphasizing a multidimensional approach that considers biological and psychosocial factors. These insights will inform the ongoing GRAPPA initiative to standardize definitions for treatment-resistant PsA, ultimately improving patient care.

<h3>Background</h3> Treatment effects on PsA joint symptoms are assessed by ACR response rates, reflecting percentages of patients (pts) meeting a composite measure of improvement from baseline (BL) at specific timepoints. Alternatively, the ACR-numeric (ACR-N) is a continuous measure of improvement based on 7 ACR components. <h3>Objectives</h3> Contrast performance of ACR response rates with ACR-N in characterizing guselkumab (GUS) treatment effect in PsA and describe duration and extent of continuous improvement with GUS using ACR-N and ACR components through week (W) 100. <h3>Methods</h3> The phase 3 DISCOVER-2 trial enrolled bio-naïve adults with active PsA (swollen and tender joint counts [SJC/TJC] ≥5, C-reactive protein [CRP] ≥0.6 mg/dL). 739 pts were randomized (1:1:1) and treated with GUS 100 mg every 4W (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo (PBO) with crossover to GUS Q4W at W24. ACR20/50/70 response rates through W100 were determined using non-responder imputation (NRI) for missing data; GUS Q4W/Q8W and PBO rates were compared through W24. Duration of continuous improvement over 100W of GUS was assessed by contrasting least square mean (LSM) ACR-N and ACR component values between consecutive visits. Percent changes in SJC, TJC, physician global (MDGA), pt global (PtGA), health assessment quality disease index (HAQ-DI), CRP, and pt-pain were also assessed, adjusting for treatment group, BL use of csDMARDs, and respective BL scores. <h3>Results</h3> ACR response rates were significantly greater with GUS Q4W/Q8W vs PBO by W4 (ACR20), W8 (ACR50), and W8-12 (ACR70); significant differences in ACR-N between GUS Q4W/Q8W vs PBO were observed by W2 (GUS Q4W) or W8 (GUS Q8W) (Table 1; nominal p&lt;0.05). Similar responses were observed with GUS Q4W and Q8W. Among GUS-treated pts, nominally significant improvements comparing ACR-N scores across consecutive visits were observed by W2, with a positive trajectory through W100 (Figure 1). Individual ACR components also significantly improved by W2 and – apart from CRP levels that rapidly plateaued to means &lt;1 mg/dL – continued to improve vs previous visit through W68-84 of GUS (nominal p&lt;0.05). <h3>Conclusion</h3> GUS rapidly improved PsA activity whether assessed by ACR response or ACR-N. Early response was apparent across ACR components, followed by a positive trajectory through 2 years of GUS that yielded low levels of residual disease. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Peter Nash Consultant of: AbbVie, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, MSD, Novartis, Pfizer, Samsung, Sun Pharma, and UCB, Grant/research support from: AbbVie, Boehringer Ingelheim, Eli Lilly, Galapagos, Gilead, GSK, Janssen, MSD, Novartis, Pfizer, Samsung, Sun Pharma, and UCB, Iain McInnes Shareholder of: Causeway Therapeutics and Evelo Compugen, Consultant of: AbbVie, Amgen, Astra Zeneca, Bristol Myers Squibb, Cabaletta, Compugen, Eli Lilly, Gilead, GSK, Janssen, Novartis, Pfizer, Roche, Sanofi, and UCB, Grant/research support from: Astra Zeneca, Amgen, Bristol Myers Squibb, Eli Lilly, GSK, Janssen, Novartis, Roche, and UCB, May Shawi Shareholder of: Johnson &amp; Johnson, Employee of: Immunology Global Medical Affairs, Janssen Pharmaceutical Companies of Johnson &amp; Johnson, Francois Nantel Shareholder of: Johnson &amp; Johnson, Consultant of: Janssen, Alexa Kollmeier Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Research &amp; Development, LLC, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Inc., Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Dafna D Gladman Consultant of: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Amgen, Eli Lilly, Janssen, Pfizer, and UCB, Atul Deodhar Speakers bureau: AbbVie, Eli Lilly, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Amgen, Aurinia, Bristol Myers Squibb, Celgene, Eli Lilly, GSK, Janssen, MoonLake, Novartis, Pfizer, and UCB, Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, and UCB.

This corrigendum is being published to correct a number of errors and imprecisions, on pages 113, 120-125 and 138, of the following article: Taher MK, Salzman T, Banal A, Morissette K, Domingo FR, Cheung AM, Cooper CL, Boland L, Zuckermann AM, Mullah MA, Laprise C, Colonna R, Hashi A, Rahman P, Collins E, Corrin T, Waddell LA, Pagaduan JE, Ahmad R, Jaramillo Garcia AP. Global prevalence of post-COVID-19 condition: a systematic review and meta-analysis of prospective evidence. Health Promot Chronic Dis Prev Can. 2025;45(3):112-38. https://doi.org/10.24095/hpcdp.45.3.02 The authors would like to clarify a few points specifically related to the referencing of results from the 2023 Canadian COVID-19 Antibody and Health Survey (CCAHS).Footnote1 These clarifications reflect refinements in how the source data are interpreted and attributed, and do not affect the core findings or conclusions of the review. Bold has been used to identify the changes and updated text.

<h3>Background</h3> Although the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is used to assess the activity of axial disease in patients (pts) with psoriatic arthritis (PsA), only one of its questions is specific to axial symptoms. Alternatively, the Ankylosing Spondylitis Disease Activity Score (ASDAS) excludes assessment of enthesitis, gives less weight to peripheral activity and is considered more objective than the BASDAI. <h3>Objectives</h3> The current post hoc analysis aimed to compare the performance of BASDAI and ASDAS in evaluating symptoms of axial involvement in pts with axial PsA (axPsA). <h3>Methods</h3> Pts enrolled in the DISCOVER-1 (D1) and DISCOVER-2 (D2) studies were adults with active PsA despite standard therapies. D1 pts had ≥3 swollen and ≥3 tender joints (SJC; TJC) and C-reactive protein (CRP) ≥0.3 mg/dL; D2 pts had SJC ≥5, TJC ≥5 and CRP ≥0.6 mg/dL. 31% of D1 pts received 1-2 prior tumor necrosis factor inhibitors; D2 pts were biologic-naïve. Pts were randomized 1:1:1 to GUS 100 mg every 4 weeks (Q4W); GUS 100 mg at W0, W4, then Q8W; or placebo with crossover to GUS Q4W at W24. axPsA was defined by presence of sacroiliitis based on previous radiograph or magnetic resonance (MR) imaging confirmation. Data were pooled across all treatment groups. In addition to BASDAI and ASDAS, modified versions excluding the peripheral arthritis and enthesitis questions (mBASDAI) and the peripheral arthritis question (mASDAS) were calculated. Normalized (scale of 0-10) versions of ASDAS and mASDAS were calculated based on maximum scores of ≈7 and ≈6.3, respectively. The correlation of BASDAI/mBASDAI and ASDAS/mASDAS with SJC, TJC, enthesitis, Functional Assessment of Chronic Illness Therapy (FACIT)-fatigue, pt pain, pt global, and physician global was assessed with Pearson’s correlation coefficient. The cross-sectional and longitudinal (W52) effects of Leeds enthesitis index (LEI), SJC, and axPsA on BASDAI/mBASDAI and ASDAS/mASDAS were assessed with mixed models. <h3>Results</h3> 436 pts with available baseline (BL) BASDAI information were included in the analysis. In pts with axPsA, BASDAI showed weak correlation with SJC, TJC, LEI, and physician global; moderate correlation with fatigue; and strong correlation with pt global and pt pain. Similar results were observed for ASDAS and modified versions. Among pts without axPsA, correlations of BASDAI and ASDAS with SJC, TJC, and LEI remained weak; correlations with pt global and pt pain remained strong. Longitudinally, among pts with and without BL enthesitis, respectively, LEI and SJC showed significant but not clinically important associations with either outcome. Presence of axial disease was associated with significantly greater BASDAI and ASDAS scores, at BL and longitudinally, without differences in the incremental effect on BASDAI, normalized ASDAS, or their modified versions. <h3>Conclusion</h3> In pts with axPsA, the BASDAI and ASDAS performed similarly, with both demonstrating weak correlations with peripheral arthritis and moderate/strong correlations with pt fatigue and pain. The BASDAI and ASDAS also showed similar ability to discern changes in axial disease activity. These results suggest that both BASDAI and ASDAS are valid, and perform comparably, in assessing activity of axial disease in PsA pts. <h3>REFERENCES:</h3> NIL. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> Xenofon Baraliakos Consultant of: AbbVie, Chugai, Eli Lilly, Galapagos, Janssen, MSD, Novartis, Pfizer, Roche, and UCB, Grant/research support from: AbbVie, MSD, and Novartis, Dafna D Gladman Consultant of: BMS, Galapagos, Gilead, and Novartis, Grant/research support from: AbbVie, Amgen, Eli Lilly, Janssen, Pfizer, UCB, Soumya D Chakravarty Employee of: Janssen Scientific Affairs, LLC and shareholder in Johnson &amp; Johnson, of which Janssen Scientific Affairs, LLC is a wholly-owned subsidiary, Cinty Gong Employee of: Janssen Scientific Affairs, LLC and shareholder in Johnson &amp; Johnson, of which Janssen Scientific Affairs, LLC is a wholly-owned subsidiary, May Shawi Shareholder of: Johnson &amp; Johnson, Employee of: Janssen Pharmaceutical Companies, a wholly-owned subsidiary of Johnson &amp; Johnson, Emmanouil Rampakakis Consultant of: Janssen, Employee of: JSS Medical Research, Mitsumasa Kishimoto Speakers bureau: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Tanabe-Mitsubishi, and UCB Pharma, Consultant of: AbbVie, Amgen, Asahi-Kasei Pharma, Astellas, Ayumi Pharma, BMS, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, Janssen, Novartis, Pfizer, Tanabe-Mitsubishi, and UCB Pharma, Enrique Soriano Speakers bureau: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Janssen, Novartis, Pfizer, Roche, and UCB, Consultant of: AbbVie, Janssen, Novartis, and Roche, Grant/research support from: AbbVie, Janssen, Novartis, Pfizer, Roche, and UCB, Philip J Mease Speakers bureau: AbbVie, Amgen, Eli Lilly, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Consultant of: AbbVie, Aclaris, Amgen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, GlaxoSmithKline, Inmagene, Janssen, Novartis, Pfizer, Sun Pharma, and UCB, Grant/research support from: AbbVie, Amgen, Bristol Myers Squibb, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, Sun Pharma, and UCB.

OBJECTIVE: The impact of the COVID-19 pandemic on patients with inflammatory rheumatic diseases, such as ankylosing spondylitis (AS), has been variable. Here, we assess disease activity and health-related quality of life (HRQoL) through the pandemic in patients with AS. METHODS: In the open-label extension (OLE) of the phase 2b BE AGILE study, patients with AS received 160 mg of subcutaneous bimekizumab every 4 weeks. We assessed Ankylosing Spondylitis Disease Activity Score with C-reactive protein (ASDAS-CRP), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Quality of Life (ASQoL) scores in the OLE immediately before and during the COVID-19 pandemic (September 2019 to April 2021). RESULTS: A total of 232 patients remained in the BE AGILE OLE and were included in this post hoc study at the start of the analysis period (September 1, 2019); 12 patients had a COVID-19 treatment-emergent adverse event, and no cases resulted in death. The number of missed bimekizumab doses due to COVID-19 (11 doses) was minimal, and missed assessments remained low (≤5%) compared with the prepandemic period. Mean ASDAS-CRP (1.8), BASDAI (2.4), and ASQoL scores (2.8) in the OLE were low at pre-pandemic baseline and remained stable at 1.7 to 1.8, 2.2 to 2.4, and 2.0 to 2.8, respectively, across successive 3-month periods immediately before and during the pandemic. ASDAS-CRP, BASDAI, and ASQoL stability was consistent across major study countries. CONCLUSION: Disease activity and HRQoL remained stable during the COVID-19 pandemic in patients with AS receiving bimekizumab in the BE AGILE OLE, with no indication of negative effects on these outcomes.

PURPOSE OF REVIEW: Mesenchymal stromal cells (MSCs) are widely utilized in preclinical and clinical studies, with over 1500 clinical trials, including applications in Covid-19 treatment. This review consolidates recent advances in understanding MSC biology, mechanisms of action, and clinical utility. RECENT FINDINGS: This review discusses recent progress made in understanding MSC biology, including immunomodulatory mechanisms mediated by microRNAs and long noncoding RNAs. Clinically, MSC therapies have shown promise in treating conditions like Covid-19-associated ARDS and several MSC therapeutic products have been approved. Single-cell analyses have shed light on MSC heterogeneity, revealing tissue-specific and conserved subpopulations influenced by the extracellular matrix. The FDA's updated recommendations on potency assays emphasize a holistic approach to quality control, reinforcing the need for a universal reference standard to improve reproducibility and clinical outcomes. In addition, to better understand their limited success in randomized clinical trials, we highlight the importance of a universal reference standard for MSC potency. SUMMARY: MSCs offer significant therapeutic potential, but addressing challenges in heterogeneity and potency standardization is essential. Advances in understanding their immune properties and clinical applications provide opportunities to refine and expand their use in regenerative medicine.

<h3>Background</h3> Hydroxychloroquine is one of the major treatment of SLE, but its effectiveness is impaired by non-adherence, reported to range from 3% to 85% in SLE patients. Our objective was to assess the associations of severe non-adherence to HCQ, objectively assessed by HCQ serum levels, and risks of SLE flares, damage, and mortality over 5 years of follow-up. <h3>Methods</h3> The SLICC Inception Cohort is a multicenter initiative (33 centers; 11 countries). Serum of patients taking HCQ for at least 3 months, sampled at enrolment or during the first-year follow-up visit, were analyzed. Severe non-adherence was defined by a serum HCQ level &lt;106 ng/ml or &lt;53 ng/ml, for daily HCQ doses of 400 or 200 mg/d, respectively. Association with the risk of a flare (defined as a SLEDAI-2K increase ≥4 points, initiation of prednisone or immunosuppressive drugs, or new renal involvement) was studied with logistic regression, and association with damage (first SLICC/ACR Damage Index (SDI) increase ≥1 point) and mortality were studied with separate Cox proportional hazard models. <h3>Results</h3> Of 1849 cohort subjects, 660 patients (88% women) were included. Median [interquartile range] serum HCQ was 388 ng/ml (244–566); 48 patients (7.3%) had severe HCQ non-adherence. No factors were clearly associated with severe non-adherence. Severe non-adherence was independently associated with flare (OR 3.38; 95% CI 1.80–6.42) and of an increase in the SDI within each of the first 3 years (HR 1.92 at 3 years; 95% CI 1.05–3.50). Eleven patients died within 5 years, including 3 with severe non-adherence (HR 5.41; 95% CI 1.43–20.39). <h3>Conclusions</h3> Severe non-adherence was independently associated with the risk of an SLE flare in the following year, with early damage and 5-year mortality. Our results suggest the benefits of testing of detecting severe non-adherence and dedicating more resources and more time to these patients, to improve their long-term prognosis.

Introduction: The abrupt COVID-19 related healthcare closures across Ontario, Canada resulted in a rapidly growing backlog of patients referred to the Provincial Rapid Access Clinics (RACs) Program, designed to manage patients suffering from unmanageable low back pain (LBP). Left untreated or poorly treated, LBP can lead to a significant burden on patients and the health system. Expeditious implementation of virtual care (VC) became a necessity, however, frontline clinicians identified lack of confidence and experience with LBP-VC. To ensure continuity in patient-centered care, a Toolkit was developed to enable delivery of a standardized guideline-based integrated LBP pathway through VC. Aims, Objectives, Theory or Methods: A coordinated in-depth multi-stakeholder engagement process was utilized to address clinicians’ concerns to promote confident adoption of VC. A system-level rapid response approach led through a centralized clinical and digital provincial infrastructure was used for Toolkit development. Toolkit structure, content and refinement was determined through an iterative mix-methods approach undertaken with provincial LBP stakeholders on how best to implement an established evidence-based shared-care LBP clinical pathway through VC. This approach facilitated acceptable strategies for barrier mitigation and enabled optimization to be rapidly developed on a provincial level with necessary resources and guidelines to deliver standardized LBP-VC across Ontario. Highlights or Results or Key Findings: Toolkit resources have been adopted across 16 urban and rural regions in Ontario. Engaging front-line clinicians, (including spine surgeons), was critical for active implementation of VC that was safe, effective, and met professional requirements. Stakeholders for operational oversight included government, hospital and regional administrators, and professional colleges and associations. With collaborative provincial leadership, barriers and enablers to LBP-VC were systematically identified. Extensive multi-stakeholder consultation which included patient feedback, provided pragmatic information related to privacy; informed consent; professional standards; regional variations, and clinical and patient barriers and enablers. Emergent themes included technology requirements, administrative processes, educational needs, and professional standards. Four hundred and forty LBP-VC patient satisfaction questionnaires were completed (June 2020-May 2021). Based on a 5-point Likert scale, (5 most positive), overall satisfaction and likelihood of participating again was 4.7/5. Qualitative analysis revealed three themes with VC, importance of human connection, patient-perceived virtual physical examination limitations and VC efficiencies. Conclusions: A Toolkit enabled a standardized province-wide approach to LBP-VC. Multi-stakeholder engagement was utilized to understand barriers, identify enablers, and ultimately promote patient and provider adoption and confidence with LBP-VC. With collaborative leadership, and extensive engagement, clinical resources and guidelines were developed and implemented province-wide with excellent face-validity based on patient and provider feedback and uptake. Implications for applicability/transferability, sustainability and limitations: There is a need to further assess patient preference for care delivery during normal and non-emergency circumstances (COVID-19). Future directions include validating LBP-VC physical examination findings compared to hands-on assessment. There is also a need to explore cost-effectiveness of LBP-VC at scale; patient-related factors including demographics, satisfaction, preference, and acceptance with LBP-VC; treatment outcomes, including surgical; safety considerations such as security of online platforms, physical patient safety during the assessment; and comparing rate of escalation to surgeon with in-person and virtual assessment.

This dataset provides revised ground truth hip bone segmentation masks for eligible hips (N = 104) in the TotalSegmentator small subset. Masks were manually corrected by the authors based on original ground truth within the TotalSegmentator dataset. Revisions were made across the full hip bone volume, with the most substantial changes in the acetabulum and sacroiliac joint regions. Details about this dataset can be found in this validation study (link to come), where these corrected segmentations serve as the ground truth for evaluating a post-processing workflow for TotalSegmentator-generated acetabular segmentations.

<h3>Background</h3> Neuropsychiatric symptoms are highly prevalent among systemic lupus erythematosus (SLE) patients, being clinically observed in up to 80% of adult and 95% of pediatric patients. Type 1 interferons, in particular interferon alpha (IFNα), have been implicated in the pathogenesis of SLE as well as its associated neuropsychiatric symptoms (NPSLE). The cellular components and molecular pathways affected within the central nervous system (CNS) in NPSLE remain unclear. Murine models of NPSLE with an elevated peripheral type 1 interferon signature are lacking, limiting studies of the mechanistic association between IFNα and behavioral phenotypes in this disease. <h3>Methods</h3> Male and female B6.Sle 1<i>yaa</i> mice were analyzed at varying ages from 10 days to 20 weeks. Both peripheral and CNS tissues were examined by RT-PCR for ISG expression. MERFISH, a spacial transcriptomic approach, was used to identify ISG expression in whole brain sections and results validated using RNA scope. To identify differentially expressed genes single nuclei were isolated from cells of hindbrain and hippocampus and analyzed by RNA sequencing. Behavior assays were used examine symptoms of anxiety and fatigue. <h3>Results</h3> We found using probe-based spatial transcriptomics that the type 1 interferon signature is present within the brain parenchyma of lupus mice as early as 3 weeks, with interferon stimulated genes (ISG) enriched in spatially distinct patches. ISG expression was validated by RT-PCR and RNA scope. Unbiased single nucleus sequencing of the murine hind brain and hippocampus revealed that ISGs as a group were the most highly differentially expressed genes. <i>Sle 1 yaa</i> male mice developed symptoms of anxiety as early as 4 weeks and fatigue by 8 weeks relative to WT controls. Behavior and ISG patch formation were not dependent on the <i>yaa</i> mutation as female mice at 20 weeks were also positive for focal patches and development behavior change. <h3>Conclusions</h3> We propose that the functional effects of interferon stimulated gene (ISG) patches play a mechanistic role in mediating behavioral phenotypes, and modulation of the type 1 interferon signaling pathway within the brain. <h3>Acknowledgement</h3> We thank NIAMS for support (R01AR072965) <h3>Lay summary</h3> A common problem in lupus is being tired and absent minded. The cause is not known. We think it is due to the same factors released by the body during a cold. We want to know how the factors get into the brain and how they affect the tissues. By using mutant mice that have lupus symptoms, we hope to find out how the factors work in the brain.