Mandana Nikpour

Background: Musculoskeletal (MSK) conditions are a leading cause of disability worldwide, yet MSK research often underrepresents diverse populations and inadequately reports considerations related to diversity, inclusion, culture, and equity. Inconsistent reporting limits the interpretability, transferability, and real-world impact of research findings, particularly for priority populations. Currently, there is no MSK-specific reporting guidance that systematically integrates equity-focused principles.Objective: To develop a DICE (Diversity, Inclusion, Culture, and Equity) Checklist, a reporting guideline designed to strengthen transparency, reflexivity, and equity considerations across all stages of musculoskeletal health research.Methods: The DICE Checklist was developed using a multi-phase, modified Delphi approach. This included (1) a short report describing existing equity-focused reporting frameworks, methods, and guidelines. (2) synthesis of key domains relevant to MSK research, and (3) iterative refinement through expert consultation (in-person workshops followed by individual follow up) involving clinicians, researchers, methodologists, and lived-experience contributors.Results: The final DICE Checklist comprises 25 recommendations across four key reporting domains spanning the research lifecycle: (1) community partnerships, leadership, and governance; (2) inclusive research design and ethical practice; (3) equity-driven data collection, analysis, and interpretation; and (4) communication and knowledge sharing. The checklist prompts authors to explicitly reflect on diversity, inclusion, culture, and equity considerations, justify methodological or practical limitations where relevant, and consider implications for generalisability, implementation, and translation. DICE is designed to complement, rather than replace, existing reporting guidelines.Conclusion: The DICE Checklist provides a practical, MSK-specific reporting tool to enhance equity-focused transparency in research. Its adoption may improve the quality, relevance, and inclusivity of musculoskeletal research, supporting more equitable evidence generation and translation into practice and policy.

Objective: We compared demographic and clinical characteristics between patients with late-onset (LO) and early-onset (EO) systemic lupus erythematosus (SLE) and examined their longitudinal associations with treatment targets and long-term outcomes, irreversible organ damage accrual, and health-related quality of life (HRQOL). Methods: We analyzed prospectively collected data from patients enrolled in the Asia Pacific Lupus Collaboration cohort. Patients diagnosed with SLE at age > 50 years were classified as having LO-SLE, whereas those diagnosed at age ≤ 50 years were classified as having EO-SLE. Longitudinal associations with treatment targets (Low Lupus Disease Activity State [LLDAS] and Definition of Remission in SLE [DORIS] remission), organ damage accrual (Systemic Lupus International Collaborating Clinics/American College of Rheumatology [SLICC/ACR] Damage Index), and HRQOL (36-item Short Form Health Survey v2 physical and mental component summary [PCS and MCS] scores) were examined using multivariable multilevel logistic, recurrent event survival, and linear mixed-effects models, respectively. Disease activity, flares, medication exposure, and other clinical characteristics were also compared between groups. Results: Among 3917 patients studied, 346 (8.8%) had LO-SLE and 3571 (91.2%) had EO-SLE. Compared to patients with EO-SLE, those with LO-SLE had lower disease activity, lower glucocorticoid and immunosuppressant exposure, and higher attainment of treatment targets. LO-SLE was associated with higher odds of attaining LLDAS (odds ratio [OR] 2.33, 95% CI 1.66-3.28) and DORIS remission (OR 2.22, 95% CI 1.45-3.38). However, patients in this group were at a greater risk of damage accrual (hazard ratio 1.82, 95% CI 1.50-2.21) and lower PCS scores, meaning poorer physical health (regression coefficient [RC] −3.63, 95% CI −4.58 to −2.68), but not MCS scores (RC 0.68, 95% CI −0.50 to 1.86). Conclusion: Despite higher attainment of treatment targets, patients with LO-SLE experienced greater damage accrual and poorer physical health, suggesting that disease activity targets alone may not fully identify outcome risk in LO-SLE.

Background/Objectives: Pulmonary arterial hypertension (PAH) occurs in >12% of systemic sclerosis (SSc) patients and has a high mortality. Annual screening for all SSc patients is the standard of care and can include spirometry (RFT), serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and echocardiography (TTE). We sought to evaluate the accuracy of NT-proBNP alone to screen for SSc-PAH. Methods: We defined groups as low, intermediate and high risk of PAH according to RFT, TTE and RHC (right heart catheter) parameters. NT-proBNP thresholds predictive of risk group were defined, and ROC curves were used to evaluate the predictive accuracy of the calculated cut-points to diagnose SSc-PAH within the following 12 months. Results: A total of 820 SSc patients had NT-proBNP recorded 12 months prior to RHC, or if no RHC had been performed, within 12 months of the most recently recorded annual visit. The majority (335, 40.85%) were assigned to low risk of PAH, 189 (23.05%) to intermediate risk and 176 (21.46%) to high risk. NT-proBNP level < 122.9 ng/L defined the low-risk group, 122.9–186.6 ng/L defined the intermediate risk and >186.6 ng/L defined the high risk. NT-proBNP ≥210 ng/L with RFT (the ‘ASIG algorithm’) had the highest predictive accuracy, with sensitivity of 86.75% (77.52–93.19%), specificity of 60.71% (58.52–62.87%), PPV of 8.47% (6.69–10.55%), NPV of 99.09% (98.38–99.55%) and AUC of 0.74 (0.70–0.78). NT-proBNP ≥ 210 ng/L alone had sensitivity of 67.05% (56.21–76.70), specificity of 71.91% (70.03–73.72), PPV of 8.25% (6.34–10.52), NPV of 98.30% (97.57–98.86) and AUC of 0.69 (0.64–0.74). NT-proBNP thresholds associated with the three defined risk groups performed similarly overall. Conclusions: NT-proBNP alone, compared to the ASIG algorithm, had a slight reduction in NPV and AUC to predict PAH within 12 months. When NT-proBNP is ≥210 ng/L, the NPV remains high (98.0%).

Background: Emerging advanced therapies are being trialled in patients with severe refractory systemic lupus erythematosus (srSLE), but this state lacks an evidence-based operational definition. We evaluated candidate srSLE definitions to determine which best identifies patients with poor outcomes.Methods: We constructed candidate srSLE definitions using varying thresholds of treatment-refractory disease activity and evaluated the definitions in the Asia Pacific Lupus Collaboration cohort. At each visit (tn), disease activity was defined using SLE Disease Activity Index (SLEDAI-2K ≥6, ≥8, ≥10, or ≥12), Physician Global Assessment (PGA ≥1 or >1), and SELENA-SLEDAI Flare Index (SFI mild-to-moderate and severe flare (MMSf) or severe flares only (Sf)). Treatment refractoriness required concurrent use of immunosuppressants (IS) at tn and tn-1 (preceding visit), together with glucocorticoids (GC, ≥5 or ≥10mg/day prednisolone equivalent), with or without concurrent anti-malarial (AM) use. Outcomes accessed at 12 months after the first visit fulfilling each definition criteria included flare, organ damage accrual (SLICC/ACR Damage Index) and non-attainment of lupus low disease activity state. Candidate definitions were ranked from highest to lowest rates for each outcome. Ten definitions were associated with highest rates across all three outcomes (‘top 10’); they were further evaluated using machine-learning–based gradient boosting models. Findings: We evaluated 80 candidate definitions (least stringent, achieved by 27% of patients, to most stringent, achieved by 1 and/or MMSf, while 4 definitions included exposure to triple therapy (GC+IS+AM). The best predictive performance on all three outcomes at 12-months was srSLE defined as SLEDAI≥6+GC≥10+IS+PGA>1+MMSf, observed in 267 (6.5%) of patients. Interpretation: We derived data-driven definitions of srSLE with strong predictive performance for poor patient outcomes. This may help standardise patient selection for trials of transformative therapies under development.

Background: Cardiopulmonary involvement in systemic lupus erythematosus (SLE) refers to a group of serious manifestations, with a high prevalence for some, such as pericarditis and pleuritis, and high mortality in others, such as lupus myocarditis (LM) and diffuse alveolar haemorrhage (DAH). There is a paucity of systematic literature reviews on the management of inflammatory cardiopulmonary manifestations in SLE. We aimed to assess the available evidence in this area. Methods: A systematic literature search was conducted from January 1990 to June 2025 using keywords related to the cardiac and pulmonary systems, SLE, and treatments. Manifestations related to atherosclerosis or anti-phospholipid syndrome were excluded. Results: A total of 67 studies, covering pericarditis, LM, pulmonary arterial hypertension (PAH), pleuritis, acute lupus pneumonitis (ALP), DAH, interstitial lung disease, and shrinking lung syndrome (SLS) were included. Glucocorticoids (GCs) were utilized as first-line treatment for all these conditions, and GC pulse was commonly administered in serious manifestations such as pericardial tamponade, LM, ALP, and DAH. Cyclophosphamide was the most used immunosuppressant, with low-to-moderate evidence indicating its effectiveness. Low-to-moderate evidence supported rituximab as a second-line therapy for LM, DAH, and SLS, and plasma exchange was commonly used in DAH. For PAH, high-quality evidence from RCTs supported the use of PAH-targeted therapies, and initial PAH-targeted combination therapy showed more benefits than monotherapy. In addition, immunosuppressive therapy may be beneficial for SLE-PAH patients, especially those with early, mild PAH. Anti-fibrotic therapy, such as nintedanib and pirfenidone, had no evidence of effectiveness in SLE-ILD. Evidence for the benefit of belimumab and anifrolumab for cardiopulmonary manifestations was also minimal. Patients with some conditions, such as LM, ALP, and DAH, had poor prognoses under current therapies, with reported short-term mortalities of up to 40%-60%. Conclusions: GC and conventional IS currently remain the most evidence-based approaches for managing most cardiopulmonary manifestations in SLE. Despite aggressive immunosuppressive therapies, patients with some conditions, such as LM, ALP, and DAH, still experience high mortality. The quality of the existing evidence and the insights into novel therapies in these patients were limited, highlighting the urgent need for RCTs and optimized management in this area.

Objectives: To determine the prevalence and predictive correlates of arthritis and joint damage in systemic lupus erythematosus (SLE) patients in the Asia-Pacific Lupus Collaboration (APLC) cohort, and to determine their impact on health-related quality of life (HRQoL). Methods: SLE patient data (2013–2020) were collected from the prospective multinational APLC cohort. We defined arthritis according to the SLE Disease Assessment Index (SLEDAI-2K) definition of persistent arthritis as arthritis in ≥2 consecutive visits, and joint damage according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) definition (deforming or erosive arthritis). HRQoL was measured by Short Form Survey (SF36). Descriptive statistics, univariable and multivariable Cox hazard models, and Kaplan–Meier analyses were performed. Results: During median 2.5 (1.0–5.1) years of follow-up, 803/4106 (19.6%) patients had arthritis at least once, and 18/3383 (0.53%) accrued joint damage. Patients with arthritis were more likely to be female, Caucasian, current smokers at enrolment, and less like to have tertiary education; they also had higher overall disease activity, and lower physical and mental HRQoL. Kaplan–Meier analysis demonstrated that joint damage was more likely in patients with arthritis. Persistent arthritis and longer follow-up were risk factors for joint damage accrual; being from high-income countries was protective. Patients with joint damage also had worse physical HRQoL. Conclusion: Arthritis in the APLC cohort was infrequent compared with other cohorts and was associated with smoking, higher overall disease activity, and damage accrual across multiple domains. Presence of arthritis significantly impacted physical and mental HRQoL. Joint damage was strongly predicted by persistent arthritis.

Objective: This research article aims to describe the prevalence, associations, and health‐related quality of life (HRQoL) impact of mucocutaneous features of systemic lupus erythematosus (SLE). Methods: Data from the Asia‐Pacific Lupus Collaboration cohort were analyzed (2013–2021). Mucocutaneous activity (MC‐A) items were rash, alopecia, and mucosal ulcers; were defined by the Systemic Lupus Erythematosus Disease Activity Index 2000; and were persistent if present for at least six months. Mucocutaneous damage (MC‐D) items were chronic skin ulceration, scarring alopecia, and skin/panniculum scarring and were defined by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index. HRQoL was measured by 36‐Item Short Form Health Survey (SF‐36) surveys. Multivariate logistic generalized estimating equation models were used to determine correlates of MC‐A at each visit. Time‐varying covariate survival models were used to determine predictors of MC‐D. Results: During a median of 2.5 (interquartile range 1.0–5.1) years’ follow‐up, 1,499 of 4,102 patients (36.5%) had MC‐A (rash n = 1,055, alopecia n = 731, mucosal ulcers n = 352) and 606 of 3,655 patients (16.6%) had persistent MC‐A. These patients were more likely to record worse mean mental (42.6 vs 44.8; P = 0.014) and physical component (41.1 vs 46.1; P < 0.001) SF‐36 scores. Being White, smoking, serologic activity, vasculitis, myositis, serositis, nephritis, and neurologic/psychiatric features were correlates of MC‐A. Of 3,647 patients, 157 (4.3%) accrued MC‐D (skin/panniculum scarring n = 53, alopecia n = 98, ulceration n = 30). These patients had worse mean physical component (39.8 vs 46.0, P = 0.001) SF‐36 scores and were more likely to be White with persistent MC‐A. Conclusion: All mucocutaneous manifestations were associated with worse HRQoL. MC‐A correlated with serologic and systemic disease activity burden in SLE. Persistent MC‐A was associated with increased risk of MC‐D, emphasizing the importance of early and effective treatment. Both MC‐A and MC‐D were more likely in White patients, suggesting ethnic and environmental impacts. Smoking was a potentially modifiable correlate of MC‐A.

Objective: The aim of this study was to determine the differences in demographic, serologic, and clinical characteristics between male and female patients with systemic sclerosis (SSc) in an Australian cohort. Methods: This was a retrospective observational study using data from the Australian Scleroderma Cohort Study. Male patients were compared to female patients using chi‐square test, Wilcoxon rank‐sum test, and Student's t ‐test. Survival analysis from time of diagnosis to all‐cause mortality was presented on Kaplan–Meier curves, and a multivariate Cox proportional hazards model was used to evaluate independent predictors of all‐cause mortality. A subanalysis of patients with incident SSc, defined as disease duration less than four years from onset of first non–Raynaud phenomenon manifestation to recruitment, was performed. Results: Of the 2,033 participants, 299 were male, with a female‐to‐male ratio of 5.8:1. Male patients were more likely to present with diffuse skin involvement (43.7% vs 23.6%, P < 0.001) and ever be positive for digital ulcers, digital pitting, gangrene, and tendon friction rubs as well as myositis and interstitial lung disease. Male patients were more likely to have anti–Scl‐70, anti–Jo‐1, anti‐PM/Scl and anti–RNA polymerase III antibodies compared to female patients. Male patients reported more exposure to silica dust, organic solvents, vinyl chloride, and epoxy resin compared with female patients. In the incident cohort, male patients had statistically significantly higher mortality, with 60% of male patients compared to 82% of female patients surviving 10 years from diagnosis ( P < 0.001). Conclusion: Male patients with SSc have more extractable nuclear antigen antibody positivity and reduced survival in comparison to female patients. The significant difference between occupational exposures recorded between sexes warrants further investigation into the role of industrial exposures in the pathogenesis of SSc in male patients. image

Objective: Gastroesophageal reflux disease (GERD) affects up to 90% of patients with systemic sclerosis (SSc). Chronic esophageal acid exposure can result in complications including the formation of esophageal strictures (ES). Proton pump inhibitors can alter gastric acid pH and improve GORD symptoms; however, there have been no recent studies evaluating the prevalence of SSc–ES since these medications became widely available. Our aim was to investigate the prevalence of SSc–ES over time and identify risk factors associated with ES. Methods: Consecutive patients from the Australian Scleroderma Cohort Study who met American College of Rheumatology/EULAR criteria for SSc were included. Clinically significant ES was defined as characteristic findings seen on gastroscopy or patient‐reported ES requiring dilatation. Multivariable logistic regression analysis was used to identify factors associated with SSc–ES. The time to SSc–ES development from SSc disease onset was evaluated using Kaplan‐Meier survival analysis. Results: ES affected 191 of 1,543 patients (12.4%) and were associated with a longer disease duration, gastric antral vascular ectasia, esophageal dysmotility, reflux esophagitis, and myocardial disease on multivariable logistic regression analysis ( P < 0.05). Compared to patients with SSc diagnosed before 1990, those who were diagnosed between 2000 and 2010 and 2010 and 2023 were significantly less likely to have clinically significant ES on multivariable logistic regression analysis (odds ratio 0.45 and 0.42, respectively; P = 0.002).The median disease duration at time of SSc–ES diagnosis increased from 3 (interquartile range 0–5) years to 11.5 (interquartile range 3.5–24) years for those diagnosed with SSc–ES before 1990 to those diagnosed after 2010 ( P = 0.0027). Conclusion: SSc–ES is associated with a longer disease duration and other gastrointestinal SSc manifestations, with prevalence decreasing over time.

Objective: Raynaud’s phenomenon (RP) is the first noticeable symptom of systemic sclerosis (SSc), appearing even years before other signs. Vascular and immune pathways, hallmarks in SSc pathogenesis, are implicated in primary RP. Hence, we aimed to define the shared genetic architecture between these conditions to explore pathogenic mechanisms and whether pleiotropic loci could help identify primary RP patients at increased genetic risk of developing SSc. Methods: We analysed genome-wide association study (GWAS) summary statistics for primary RP (4 986 cases and 850 981 controls) and SSc (10 654 cases and 18 043 controls). We performed a cross-trait meta-analysis (∼8.6M single nucleotide polymorphisms) to identify variants associated with both diseases. Functional annotation was used to prioritise potential causal genes. We also constructed a polygenic risk score (PRS) to assess clinical implications. Results: Beyond the well-known HLA associations, we identified five additional pleiotropic loci, including MEOX2 as a novel association for both traits with opposing effects, ADRA2A representing a novel genetic factor for SSc, and IL12A, NFKB1 and TNIP1 as novel loci for primary RP. Functional annotation highlighted vascular and inflammatory pathways. Finally, the PRS model shows modest discrimination (area under the curve = 0.57). However, it allows the identification of primary RP individuals at high genetic risk of developing SSc (75th percentile, relative risk =1.29 [95% CI 1.02, 1.62]; P-value= 3.58 × 10−2). Conclusion: This study reveals a genetic link between primary RP and SSc, identifying five novel pleiotropic loci and supporting the potential of genetic profiling for early risk assessment and personalised monitoring strategies.