Risk factors for damage accrual in primary antiphospholipid syndrome: A retrospective single-center cohort study.

BACKGROUND: Despite anticoagulant therapy, a antiphospholipid syndrome (APS) has a higher rate of recurrent events, which can lead to damage accrual and a negative impact on life quality. OBJECTIVES: To evaluate the risk factors and APS subsets associated with damage accrual. PATIENTS/METHODS: We conducted a retrospective single-center study. We reviewed the medical records of 282 APS patients, with a median age of 36 (IQR 30-46) years and a median of 195 (IQR 137-272) months. The primary endpoint was damage accrual during follow-up, defined as organ/tissue impairment present for at least six months or causing permanent loss. The secondary endpoints were early organ damage within six months of disease onset and death. RESULTS: Eighty (28.4%) patients presented damage accrual; 52.5% developed damage within six months of APS onset, and 41.3% had more than one organ involved. Neuropsychiatric involvement, affecting 38.8% of the patients, was the most frequent, followed by peripheral vasculopathy and renal involvement, 35% either. Death happened in 7 (2.5 %) patients; damage accrual was associated with a 6-fold risk of death [OR 6.7 (95% CI 1.3-35.1), p = 0.03]. Microangiopathy and non-criteria manifestations were independent risk factors for damage accrual with 5-fold and 4-fold higher risk, respectively [(OR 4.9 (95% CI 2.1-11.7), p < 0.0001 and (OR 3.8 (95% CI 1.5-10.1), p = 0.007]. The cumulative incidence of damage accrual increased by 5.7-fold and 3.6-fold in patients with microangiopathy and non-criteria manifestations. CONCLUSIONS: APS patients had a higher frequency of damage accrual. Microangiopathy and non-criteria manifestations were independent risk factors for damage accrual.

Circulating extracellular vesicles and small non-coding RNAs cargo in idiopathic inflammatory myopathies reveal differences across myositis subsets.

OBJECTIVE: To investigate the epigenetic footprint of idiopathic inflammatory myopathies (IIM) through characterization of circulating extracellular vesicles (EVs) and the expression of EV-derived small non-coding RNAs (sncRNAs). METHODS: In this cross-sectional study, EVs were isolated by size-exclusion chromatography from plasma of patients with IIM and age- and sex-matched healthy donors (HD). EV-derived sncRNAs were sequenced and quantified using Next-Generation Sequencing (NGS). Following quality control and normalization, filtered count reads were used for differential microRNA (miRNA) and piwi-interacting RNA (piRNA) expression analyses. Putative gene targets enriched for pathways implicated in IIM were analyzed. Patients' clinical and laboratory characteristics at the time of sampling were recorded. RESULTS: Forty-seven IIM patients and 45 HD were enrolled. MiR-486-5p (p < 0.01), miR-122-5p, miR-192-5p, and miR-32-5p were significantly upregulated (p < 0.05 for all), while miR-142-3p (p < 0.001), miR-141-3p (p < 0.01), let-7a-5p (p < 0.05) and miR-3613-5p (p < 0.05) downregulated in EVs from IIM patients versus HD. MiR-486-5p was associated with raised muscle enzymes levels. Several target genes of up/downregulated miRNAs in IIM participate in inflammation, necroptosis, interferon and immune signaling. Six piRNAs were significantly dysregulated in IIM EVs versus HD (p < 0.05). Within IIM, miR-335-5p was selectively upregulated and miR-27a-5p downregulated in dermatomyositis (n = 21, p < 0.01). Finally, plasma EV levels were significantly increased in cancer-associated myositis (CAM, n = 12) versus non-CAM IIM (n = 35, p = 0.02) and HD (p < 0.01). EVs cargo in CAM was significantly enriched of let-7f-5p and depleted of miR-143-3p. CONCLUSION: Through an unbiased screening of EV-derived sncRNAs, we characterize miRNAs and piRNAs in the EVs cargo as potential biomarkers and modifiers of diverse IIM phenotypes.

Very low dose glucocorticoid therapy in rheumatoid arthritis: Impact of b/tsDMARDs initiation timing on glucocorticoid withdrawal.

OBJECTIVES: We investigated the effectiveness and safety of very low-dose (<5 mg daily) glucocorticoids (GCs) in patients with RA treated with biological and targeted synthetic disease-modifying anti-rheumatic drugs (b/tsDMARDs). METHODS: In this prospective cohort study, we included all RA patients who started their first b/tsDMARDs at our institution between 2015 and 2020 and were monitored every 6 months for 3 years. Relationships between exposure to very low-dose GCs and disease activity were examined through multivariable logistic regression and repeated-measures analysis of variance. The impact of very low-dose GCs on safety was also evaluated. RESULTS: We enrolled 229 RA patients, of whom 68% were prescribed very low-dose GCs and 32% received no GCs. After three years on b/tsDMARDs, 32% had never abandoned, 20% had gone on and off, and 23% had permanently discontinued very low-dose GCs, while 25% had never taken GCs. Shorter disease duration at b/tsDMARD initiation was the single modifiable predictor of very low-dose GCs cessation (OR 1.1, 95% CI 1.03-1.14 for any 1-year decrease; p= 0.001). A significant association existed between ongoing utilization of very low-dose GCs and persistent moderate disease activity. Use of very low-dose GCs was associated with hypertension (20% vs 11%) and myocardial infarction (2.3% vs 0%). CONCLUSION: A substantial proportion of RA patients treated with b/tsDMARDs continue to receive very low-dose GCs without significantly improving disease control. However, this appears to increase cardiovascular morbidity.

A path to Glucocorticoid Stewardship: a critical review of clinical recommendations for the treatment of systemic lupus erythematosus.

Glucocorticoids (GCs) have revolutionized the management of SLE, providing patients with rapid symptomatic relief and preventing flares when maintained at low dosages. However, there are increasing concerns over GC-associated adverse effects and organ damage, which decrease patients' quality of life (QOL) and increase healthcare costs. This highlights the need to balance effective GC use and minimize toxicity in patients with SLE. Herein, we provide an overview of the theoretical considerations and clinical evidence, in addition to the variations and similarities across nine national and eight international recommendations regarding the use of GCs across SLE manifestations and how these compare with real-world usage. In line with this, we propose possible actions toward the goal of GC Stewardship to improve the QOL for patients with lupus while managing the disease burden.

Therapeutic Strategies and Outcomes in Neuropsychiatric Systemic Lupus Erythematosus: An International Multicenter Retrospective Study.

OBJECTIVES: The management of neuropsychiatric systemic lupus erythematosus (NPSLE) poses considerable challenges due to limited clinical trials. Therapeutic decisions are customized based on suspected pathogenic mechanisms and symptom severity. This study aimed to investigate therapeutic strategies and disease outcome for patients with NPSLE experiencing their first neuropsychiatric (NP) manifestation. METHODS: This retrospective cohort study defined NP events according to the American College of Rheumatology case definition, categorizing them into three clusters: central/diffuse, central/focal and peripheral. Clinical judgment and a validated attribution algorithm were used for NP event attribution. Data included demographic variables, SLE disease activity index, cumulative organ damage, and NP manifestation treatments. The clinical outcome of all NP events was determined by a physician seven-point Likert scale. Predictors of clinical improvement/resolution were investigated in a multivariable logistic regression analysis. RESULTS: The analysis included 350 events. Immunosuppressants and corticosteroids were more frequently initiated/escalated for SLE-attributed central diffuse or focal NP manifestations. At 12 months of follow-up, 64% of patients showed a clinical improvement in NP manifestations. Focal central events and SLE-attributed manifestations correlated with higher rates of clinical improvement. Patients with NP manifestations attributed to SLE according to clinical judgment and treated with immunosuppressants had a significantly higher probability of achieving clinical response (OR 2.55, 95%CI 1.06-6.41, p= 0.04). Age at diagnosis and focal central events emerged as additional response predictors. CONCLUSION: NP manifestations attributed to SLE by clinical judgment and treated with immunosuppressants demonstrated improved 12-month outcomes. This underscores the importance of accurate attribution and timely diagnosis of NPSLE.

Anifrolumab in Refractory Systemic Lupus Erythematosus: A Real-World, Multicenter Study.

OBJECTIVE: To report real-world experience on the use of anifrolumab (ANI) in refractory systemic lupus erythematosus (SLE). METHODS: The present study is a multicenter, retrospective study involving 9 Italian SLE referral centers participating in a compassionate use program for the use of ANI in adult patients with active SLE in whom all the available treatment choices failed, were not tolerated, or were contraindicated. At baseline and 1, 3, 6, 9, and 12 months of treatment, overall and organ-specific disease activity, flares, daily glucocorticoid (GC) dose, and adverse events were recorded. RESULTS: A total of 26 patients were enrolled. At 4 weeks after starting ANI, a significant decrease in the Systemic Lupus Erythematosus Disease Activity Index 2000 (P = 0.01), Systemic Lupus Erythematosus-Disease Activity Score (P = 0.01), and physician global assessment (P = 0.001) was recorded, and the same trend was maintained over time. A significant reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index-activity (P < 0.001) and in tender (P = 0.03) and swollen (P = 0.02) joint counts was also recorded. At 3 months of follow-up, 33% of patients already achieved a remission state, whereas 46% were in Lupus Low Disease Activity State (LLDAS); at 6 months, 50% were in remission and 80% were in LLDAS. A significant reduction in the mean GC daily dose was observed, starting from week 4 (P = 0.04). A total of 4 disease flares according to the Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index were recorded (3 mild-moderate and 1 severe). Overall, 4/20 patients with at least 24 weeks of follow-up (20%) were considered nonresponders. CONCLUSION: This study provides real-world experience on the use of ANI in patients with refractory SLE, confirming its rapid effectiveness and an overall acceptable safety profile.

A protocol for scoping reviews on the role of whole-body and dedicated body-part magnetic resonance imaging for assessment of adult and juvenile idiopathic inflammatory myopathies.

Currently, standardized magnetic resonance imaging (MRI) scoring systems and protocols for assessment of idiopathic inflammatory myopathies (IIMs) in children and adults are lacking. Therefore, we will perform a scoping review of the literature to collate and evaluate the existing semi-quantitative and quantitative MRI scoring systems and protocols for the assessment and monitoring of skeletal muscle involvement in patients with IIMs. The aim is to compile evidence-based information that will facilitate the future development of a universal standardized MRI scoring system for both research and clinical applications in IIM. A systematic search of electronic databases (PubMed, EMBASE, and Cochrane) will be undertaken to identify relevant articles published between January 2000 and October 2023. Data will be synthesized narratively. This scoping review seeks to comprehensively summarize and evaluate the evidence on the scanning protocols and scoring systems used in the assessment of diagnosis, disease activity, and damage using skeletal muscle MRI in IIMs. The results will allow the development of consensus recommendations for clinical practice and enable the standardization of research methods for the MRI assessment of skeletal muscle changes in patients with IIMs.

The diagnostic accuracy of community spine radiology for adolescent idiopathic scoliosis brace candidates.

PURPOSE: The study aims to establish the diagnostic accuracy of community spine x-rays for brace candidates. METHODS: A review of adolescent idiopathic scoliosis patients seen for initial visit at a tertiary care pediatric hospital was conducted (n = 170). The index test was the pre-referral community spine x-ray interpreted by a community radiologist. Measures of diagnostic accuracy for the index test were determined against the reference standard if images were obtained within 90 days (n = 111). The reference standard was the 3-foot standing EOS spine x-ray evaluated by spine specialists. Diagnostic criterion for a brace candidate was dichotomized by Cobb angle range (25-40°) according to Scoliosis Research Society criteria. Risser stage was not included given significant missing data in index reports. To mitigate the uncertainty around true progression, sensitivity analyses were conducted on a sub-sample of data when index test was within 60 days of the reference standard (n = 67). RESULTS: Accuracy of the community spine x-ray to detect a brace candidate was 65.8% (95% CI 56.2-74.5). Sensitivity of the index test was 65.4% with a false negative rate of 34.6%. Specificity was 66.1% with a false positive rate of 33.9%. Positive and negative predictive values were 63.0% and 68.4%, respectively. Of the total number of brace candidates (n = 52), 32.7% were missed because of underestimation in Cobb angle (95% CI 21.5-46.2). The proportion of missed brace candidates because of underestimation was unchanged with 60-day data (p = 0.37). CONCLUSIONS: Inaccuracies in community spine radiology may lead to missed opportunities for non-operative treatment.

Pre- and post-COVID-19 gender trends in authorship for paediatric radiology articles worldwide: a systematic review.

BACKGROUND: Gender inequalities in academic medicine persist despite progress over the past decade. Evidence-based targeted interventions are needed to reduce gender inequalities. OBJECTIVE: This systematic review aimed to investigate the impact of COVID-19 on gender trends in authorship of paediatric radiology research worldwide. MATERIALS AND METHODS: This prospectively registered, PRISMA-compliant systematic review searched the following databases: PubMed, MEDLINE, Web of Science, and Scopus from January 1, 2018, to May 29, 2023, with no restrictions on country of origin. Screening and data extraction occurred independently and in duplicate. Gender of first, last, and corresponding authors were determined using an artificial intelligence-powered, validated, multinational database ( www.genderize.io ). Two time periods were categorised according to the Johns Hopkins Center for Systems Science and Engineering: pre-COVID (prior to March 2020) and peak and post-COVID (March 2020 onwards). One-sample binomial testing was used to analyse proportion of authorship based on gender. Categorical variables were described as frequencies and percentages, and compared using testing chi-square or Fisher exact testing, with a threshold of P<0.05 representing statistical significance. RESULTS: In total, 922 articles were included with 39 countries represented. A statistically significant difference in authorship based on gender persisted during the peak and post-COVID time period (March 2020 onwards) where women represented a statistically significant lower proportion of last (35.5%) and corresponding (42.7%) authors (P<0.001, P=0.001, respectively). Statistically significant differences for first authors were not found in either period (P=0.08 and P=0.48). CONCLUSION: This study identifies differences in gender trends for authorship in paediatric radiology research worldwide. Future efforts to increase authorship by women are needed.

Autoantibodies Targeting G-Protein-Coupled Receptors: Pathogenetic, Clinical and Therapeutic Implications in Systemic Sclerosis.

Systemic sclerosis (SSc) is a multifaceted connective tissue disease whose aetiology remains largely unknown. Autoimmunity is thought to play a pivotal role in the development of the disease, but the direct pathogenic role of SSc-specific autoantibodies remains to be established. The recent discovery of functional antibodies targeting G-protein-coupled receptors (GPCRs), whose presence has been demonstrated in different autoimmune conditions, has shed some light on SSc pathogenesis. These antibodies bind to GPCRs expressed on immune and non-immune cells as their endogenous ligands, exerting either a stimulatory or inhibitory effect on corresponding intracellular pathways. Growing evidence suggests that, in SSc, the presence of anti-GPCRs antibodies correlates with specific clinical manifestations. Autoantibodies targeting endothelin receptor type A (ETAR) and angiotensin type 1 receptor (AT1R) are associated with severe vasculopathic SSc-related manifestations, while anti-C-X-C motif chemokine receptors (CXCR) antibodies seem to be predictive of interstitial lung involvement; anti-muscarinic-3 acetylcholine receptor (M3R) antibodies have been found in patients with severe gastrointestinal involvement and anti-protease-activated receptor 1 (PAR1) antibodies have been detected in patients experiencing scleroderma renal crisis. This review aims to clarify the potential pathogenetic significance of GPCR-targeting autoantibodies in SSc, focusing on their associations with the different clinical manifestations of scleroderma. An extensive examination of functional autoimmunity targeting GPCRs might provide valuable insights into the underlying pathogenetic mechanisms of SSc, thus enabling the development of novel therapeutic strategies tailored to target GPCR-mediated pathways.

Correlative Assessment of Machine Learning-Based Cobb Angle Measurements and Human-Based Measurements in Adolescent Idiopathic and Congenital Scoliosis.

Purpose: Scoliosis is a complex spine deformity with direct functional and cosmetic impacts on the individual. The reference standard for assessing scoliosis severity is the Cobb angle which is measured on radiographs by human specialists, carrying interobserver variability and inaccuracy of measurements. These limitations may result in lack of timely referral for management at a time the scoliotic deformity progression can be saved from surgery. We aimed to create a machine learning (ML) model for automatic calculation of Cobb angles on 3-foot standing spine radiographs of children and adolescents with clinical suspicion of scoliosis across 2 clinical scenarios (idiopathic, group 1 and congenital scoliosis, group 2). Methods: We retrospectively measured Cobb angles of 130 patients who had a 3-foot spine radiograph for scoliosis within a 10-year period for either idiopathic or congenital anomaly scoliosis. Cobb angles were measured both manually by radiologists and by an ML pipeline (segmentation-based approach-Augmented U-Net model with non-square kernels). Results: Our Augmented U-Net architecture achieved a Symmetric Mean Absolute Percentage Error (SMAPE) of 11.82% amongst a combined idiopathic and congenital scoliosis cohort. When stratifying for idiopathic and congenital scoliosis individually a SMAPE of 13.02% and 11.90% were achieved, respectively. Conclusion: The ML model used in this study is promising at providing automated Cobb angle measurement in both idiopathic scoliosis and congenital scoliosis. Nevertheless, larger studies are needed in the future to confirm the results of this study prior to translation of this ML algorithm into clinical practice.

Increasing Diversity in Canadian Radiology: From the Hiring Process to Needed Active Retention Efforts.

The Canadian Association of Radiologists supports equity, diversity, and inclusion (EDI) in employment. It is imperative that institutions implement recruitment and retention practices to ensure a diverse workforce. This requires considerable attention to each step in the process, including the job posting, candidate search, hiring committee composition, interviews, hiring decision, and retention and promotion. Job postings must be widely distributed and visible to underrepresented groups. The candidate search should be completed by a diverse committee with expertise in EDI. All committee members must complete EDI and anti-bias training and conduct a broad search that ensures underrepresented groups are encouraged to apply. Interviews must be offered to all candidates. The hiring decision must avoid the use of subjective criteria. Recruitment of members of underrepresented groups ensures a diverse workforce, and organizations should commit resources to the retention and promotion of these members. Mentorship programs must be implemented and incentives provided to faculty members to serve as mentors. Transparent guidelines for promotion made universally available on department or institution websites. Recruiting a diverse workforce in Medical Imaging will only be achieved if EDI are central to the organization's goals and strategic plan. All organizational policies, practices, and procedures must be reviewed with an intersectional lens to identify potential gaps, areas for improvement, and areas of strength in the recruitment and retention of members of underrepresented groups.

Synovial Fluid from Patients with Osteoarthritis Shows Different Inflammatory Features Depending on the Presence of Calcium Pyrophosphate Crystals.

The role of calcium pyrophosphate (CPP) crystals in osteoarthritis (OA) is still a matter of debate. With this study we aimed to investigate the inflammatory features of synovial fluid (SF) collected from patients with OA with CPP crystals compared with those without crystals. We also explored the effect of OA SF on monocytes response. SFs were collected from adult patients with OA and subdivided according to the presence of crystals. Local cellular and humoral inflammatory mediators were analysed in the SF samples. The expression levels of IL-1ß, IL-18, CASP-1, NLRP3, and GAPDH were measured by RT-PCR in the cells obtained by pelleting the SF samples. For the in vitro study, a monocytic cell line was treated with selected SF samples. SF with CPP crystals showed a significant increase in inflammatory cellular indices and higher levels of IL-1ß, IL-8, and caspase-1 transcript with respect to SF without crystals. Higher concentrations of VEGF were also observed in the early stages of the whole OA patients. THP-1 cells stimulated with OA SF released a significant amount of IL-1 ß in culture supernatants. This study demonstrated that SF collected from patients with OA shows different inflammatory features depending on the presence of CPP crystals.

Cultivating the next generation of healthcare leaders: reflections from an established healthcare leader.

BACKGROUND: Dr Andrea Doria is Professor and Vice-Chair of Radiology (Clinical Practice Improvement) at the University of Toronto, Research Director, Senior Scientist and Imaging Lead of Personalised Child Health, The Hospital for Sick Children (SickKids), Toronto, Canada. Over the past few decades, Dr Doria has established a track record of healthcare leadership. Based on Dr Doria's extensive leadership experience, she believes it is essential for established healthcare leaders to be involved in cultivating emerging healthcare leaders. METHODS: An interview was conducted with Dr Doria to learn about key lessons she believes are essential for healthcare leaders to help develop the next generation. Dr Doria reflected on her leadership style and experiences, sharing what has worked to improve the effectiveness of her teams. RESULTS: Key messages were reflected upon, including practical ways for senior leaders to support the next generation; leadership insights gained from the pandemic; the importance of building diversity in teams and nurturing leaders from underrepresented minorities; challenges to be aware of for the future of healthcare leadership; finding inspiration from team members and essential traits for healthcare leaders. CONCLUSION: Through cultivating the next generation of healthcare leaders, established leaders can be involved in establishing a brighter future for healthcare. This article describes reflections and practical takeaways that can help established leaders support emerging leaders and build their leadership skills.

Adult-Onset Still's Disease (AOSD): Advances in Understanding Pathophysiology, Genetics and Emerging Treatment Options.

Adult-onset Still's disease (AOSD) is a multisystemic complex disorder clinically characterised by episodes of spiking fever, evanescent rash, polyarthritis or diffuse arthralgias; multiorgan involvement may develop according to the hyper-inflammatory extent. The pathogenesis of AOSD is not completely recognised. The central role of macrophage activation, which results in T helper 1 (Th1) cell cytokine activation, is well established. Pro-inflammatory cytokines such as interleukin (IL)-1, IL-6 and IL-18 play a fundamental role in disease onset and progression. The disease may develop in both children and adults with overlapping clinical features, and although several subsets depending on the clinical manifestations and the cytokines expressed have been identified, the dichotomy between systemic juvenile idiopathic arthritis (sJIA) and AOSD nowadays has been overcome, and the pathology is considered a disease continuum between ages. Various therapeutic approaches have been evaluated thus far, and different compounds are under assessment for AOSD treatment. Historically, glucocorticoids have been employed for treating systemic manifestations of Still's disease, while conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) demonstrated efficacy in controlling the articular manifestations. Currently, biological (b) DMARDs are widely employed; IL-1 inhibitors such as anakinra and canakinumab have proven to have high efficacy and an excellent safety profile and the anti-IL-6 tocilizumab is approved for sJIA, with several trials and longitudinal studies confirming its efficacy and safety. Moreover, in the light of the 'window of opportunity', new evidence showed that the earlier these treatments are initiated, the sooner clinical inactivity can be achieved. Other treatment options are being considered since several molecules involved in the disease pathophysiology can be targeted through various mechanisms. This review will provide a broad overview of AOSD pathophysiology, insights into specific organ manifestations and the currently available treatments with the identification of potential therapeutic targets involved in AOSD pathogenesis will be outlined.

Systemic Lupus Erythematosus Disease Activity Score Remission and Low Disease Activity States Discriminate Drug From Placebo and Better Health-Related Quality of Life.

OBJECTIVE: Our objective was to evaluate the ability of Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) remission and low disease activity (LDA) to discriminate active drug from placebo and to discriminate outcomes in the patients' perspective (health-related quality of life [HR-QoL]) in SLE trials. METHODS: This was a post hoc analysis of the pooled Belimumab in Subjects With SLE (BLISS)-52 (NCT00424476) and BLISS-76 (NCT00410384) trials data. SLE-DAS remission and LDA attainment and discrimination between belimumab and placebo at 52 weeks were compared using chi-square tests. At week 52, 36-item Short Form Health Survey (SF-36) and Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) scores were compared between patients attaining SLE-DAS remission versus nonremission and SLE-DAS LDA versus non-LDA using the t-test and Mann-Whitney test. Mean changes from week 0 to 52 in SF-36 and FACIT-F scores were compared between groups using multivariate regression analysis adjusted for baseline scores. RESULTS: At week 52, significantly more patients attained SLE-DAS LDA taking belimumab 1 mg/kg (17.9% vs 13.0%; P = 0.023; odds ratio [OR] 1.459; relative risk [RR] 1.377; number needed to treat [NNT] 20.4) and 10 mg/kg (21.7% vs 13.0%; P < 0.001; OR 1.853; RR 1.668; NNT 11.5) compared with placebo. Likewise, more patients attained SLE-DAS remission taking belimumab 10 mg/kg compared to placebo (14.7% vs 10.1%; P = 0.019; OR 1.532; RR 1.454; NNT 21.7). At week 52, patients attaining SLE-DAS remission and LDA presented higher SF-36 domain and summary scores (all P < 0.001) and FACIT-F scores (both P < 0.001). Mean improvements from baseline in SF-36 and FACIT-F scores were significantly higher in patients achieving SLE-DAS remission and LDA. CONCLUSION: SLE-DAS remission and LDA showed discriminant ability for identifying patients receiving active drug in SLE clinical trials. Attainment of these SLE-DAS targets are associated with better HR-QoL.

Monoclonal antibodies targeting interleukins for systemic lupus erythematosus: updates in early clinical drug development.

INTRODUCTION: The advent of biological therapies has already revolutionized treatment strategies and disease course of several rheumatologic conditions, and monoclonal antibodies (mAbs) targeting cytokines and interleukins represent a considerable portion of this family of drugs. In systemic lupus erythematosus (SLE) dysregulation of different cytokine and interleukin-related pathways have been linked to disease development and perpetration, offering palatable therapeutic targets addressable via such mAbs. AREAS COVERED: In this review, we provide an overview of the different biological therapies under development targeting cytokines and interleukins, with a focus on mAbs, while providing the rationale behind their choice as therapeutic targets and analyzing the scientific evidence linking them to SLE pathogenesis. EXPERT OPINION: An unprecedented number of clinical trials on biological drugs targeting different immunological pathways are ongoing in SLE. Their success might allow us to tackle present challenges of SLE management, including the overuse of glucocorticoids in daily clinical practice, as well as SLE heterogenicity in treatment response among different individuals, hopefully paving the way toward precision medicine.

Is sarcopenia a real concern in ankylosing spondylitis? A systematic literature review.

PURPOSE: Sarcopenia is a condition defined as loss of muscle mass and strength, associated with poor functional performance and disability. Sarcopenia can be exacerbated or worsened in presence of inflammation, sedentary lifestyle and cytokine imbalance, thus it frequently occurs in people affected by rheumatic diseases. This systematic literature review aims to explore the association between sarcopenia and spondyloarthritis (SpA) and its most frequent manifestation, i.e. ankylosing spondylitis (AS). METHODS: The Scopus, PubMed, and Web of Science databases were searched for articles on muscle mass, muscle strength and axial SpA, from any date to November 2023. Only studies written in English were considered. The methodological quality of the studies included in the review was evaluated using the Newcastle-Ottawa Scales for observational studies and for case-control studies. RESULTS: 190 papers were retrieved from the searches, 14 of which met the inclusion criteria. Rather than diagnosis of sarcopenia, pre-sarcopenia or probable sarcopenia were frequent in people with AS, with a great reduction especially of muscle strength. The pre-sarcopenia status appears to be related to high AS disease activity, suggesting that chronic inflammation resulting in pain, less movement and decreased physical activity could play a role in the muscle heath of AS patients. CONCLUSIONS: Our review confirms the existence of an association between AS and loss of muscle strength-likely sarcopenia-already at a young age. Preventive and early strategies should be adopted to ensure successful aging for individuals with AS.