EULAR recommendations for the management of systemic lupus erythematosus: 2023 update.

OBJECTIVES: To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence. METHODS: An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item. RESULTS: The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease. CONCLUSION: The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion.

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.

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.

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.

The SLE-DAS provides an accurate and feasible flare tool in the clinical setting: a validation study.

OBJECTIVE: To assess the criterion validity of the SLE disease activity score (SLE-DAS) flare tool and compare its performance in identifying flares against other instruments. METHODS: Patients with SLE fulfilling SLE-DAS low disease activity at baseline were included from two academic lupus clinics. During follow-up, flares were identified by the senior attending clinician, applying the expert-consensus-based definition as gold-standard. The first clinical flare from flaring patients, and the first visit after baseline in patients without flares were analysed. In each no flare/flare visits, we assessed flares by SLE-DAS (score increase ≥1.72), classic-SELENA Flare Index (c-SELENA FI), revised-SELENA FI (r-SELENA FI), and SLEDAI-2K (score increase ≥4). We estimated the sensitivity, specificity, and Cohen's Kappa agreement of each flare tool against the gold-standard. RESULTS: A total of 442 patients were included and followed-up for 22.9 (14.2) months. Incidence of flares was 8.19/100 patient-years, with 69 patients experiencing flares. The SLE-DAS identified 96.6% of the expert-defined flares implying a treatment change and classified 28.0% of those as moderate/severe. Sensitivity and specificity for the gold-standard flare definition were: SLE-DAS 97.1% and 97.3%, c-SELENA FI 88.4% and 98.1%, r-SELENA FI 88.4% and 96.8%, SLEDAI-2K 56.5% and 99.2%, respectively. Kappa coefficients of these instruments were 0.902 (95% CI: 0.847, 0.957), 0.870 (95% CI: 0.805, 0.935), 0.832 (95% CI: 0.761, 0.903), and 0.663 (95% CI: 0.557, 0.769), respectively. The number of flare misclassifications was lowest with the SLE-DAS, and highest with the SLEDAI-2K. CONCLUSION: The SLE-DAS accurately identifies and categorizes flares as mild or moderate/severe. It is feasible and, thus, may help the physicians' treatment decisions in the clinical practice setting.

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.

Mining for Gems: Early Detection of Calcinosis in Juvenile Dermatomyositis Using Low-Dose Computed Tomography.

Calcinosis, a common complication in juvenile dermatomyositis (JDM), affects up to 40% of patients and can be associated with uncontrolled disease activity and morbidity.1A 9-year-old female with a 17-month history of JDM presented with worsened bilateral knee pain.

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.

Diagnostic pathway and treatment preferences for systemic lupus erythematosus: a physician-based discrete choice experiment.

OBJECTIVES: To assess physicians' preferences on diagnostic pathways and treatment priorities for systemic lupus erythematosus (SLE) using a discrete choice experiment (DCE). METHODS: A board of 11 SLE experts and a DCE expert statistician defined informative profiles of diagnostic pathways, pharmacological therapies, and two distinct profiles of mild-moderate and severe SLE. An independent panel of 115 clinicians involved in SLE management was invited to participate. Parameter estimates from the model were interpreted as relative preference weights (PWs). The mean PWs were used to calculate each attribute's relative importance (RI). RESULTS: 95 clinicians (57% females, 71% rheumatologists) completed the DCEs. The DCEs could not identify a hierarchy of importance among diagnostic pathway attributes. Nevertheless, "referral time to a rheumatologist" was considered more important for mild-moderate (RI=25%) and severe (RI=20%) SLE. Among the therapeutic attributes, the effect on organ damage progression after 12 months showed the highest preference for mild-moderate (RI=35%) and severe (RI=41%) SLE patients, followed by reduction in disease activity levels (max RI=19%) and glucocorticoid dose (max RI=13%) after six months. Reducing prednisone dose below 5 mg/day scored higher utility levels for mild-moderate (PW=66.1) than severe (PW=14.2) SLE. Administration route, action rapidity, patient-global assessment, and serious infection risk showed lesser relevance (RI 7-8%). No distinctions were found among subgroups categorised by the clinicians' areas of expertise. CONCLUSIONS: These DCEs highlight a high degree of awareness among lupus-treating physicians, with no differences across medical specialties, of the unmet need for early diagnosis and prevention of damage accrual in SLE management.

Preferences for diagnostic pathways and treatment choice in systemic lupus erythematosus: a patient-based discrete choice experiment.

OBJECTIVES: Starting from the unmet need of early diagnosis and treatment in systemic lupus erythematosus (SLE), the study aims to explore patient preferences in diagnostic pathways and treatment modalities. It seeks to integrate clinical priorities with patient perspectives, providing an optimal approach to SLE treatment that remains uncertain. METHODS: A discrete choice experiment (DCE) has been conducted to investigate whether patient preferences align while maintaining consistent attributes and levels, providing a direct assessment of relative preferences and hypothetical treatment approaches in SLE. RESULTS: DCE results demonstrated that obtaining an early diagnosis is the most crucial attribute for patients. Additionally, a multidisciplinary care team, capable of enhancing clinical outcomes and patient satisfaction, is essential, along with a clinical centre conveniently located within 30 minutes of the patient's home. Lastly, patients prefer the opportunity to reduce glucocorticoid to a dosage ≤5 mg/day, and eventually discontinue, aligning with the new EULAR recommendations, and favour oral and subcutaneous routes of administration for new course of treatment. CONCLUSIONS: Patient preferences contribute to enhancing the care pathway for SLE by optimising disease management, with a focus on multidisciplinarity and psychological support.

Comorbidities in the Spondyloarthritis GISEA Cohort: an average treatment effect analysis on patients treated with bDMARDs.

OBJECTIVES: We aimed to investigate the effectiveness of tumour necrosis factor inhibitors (TNFi), anti-interleukin-17 or interleukin-12/23 monoclonal antibodies (anti-IL) on comorbidities in a cohort of patients with spondyloarthritis (SpA), using an average treatment effect (ATE) analysis. METHODS: SpA patients from the multicentre Italian GISEA Registry were divided into groups according to pharmacological exposure: no treatment (G0), TNFi (G1) and non-responders to TNFi switched to anti-IL (G2). In each group, we recorded the prevalence and incidence of infectious, cardiopulmonary, endocrinological, gastrointestinal, oncologic, renal and neurologic comorbidities. Each comorbidity was then fitted for ATE and baseline features were evaluated for importance. RESULTS: The main findings of this study comprising 4458 SpA patients relate to cancer, other gastrointestinal diseases (OGID) and fibromyalgia. ATE showed no increased risk of solid cancer in G1 (0.42 95% CI 0.20-0.85) and G2 (0.26 95% CI 0.08-0.71) vs. G0, with significantly higher incidence in G0 (14.07/1000 patient-years, p=0.0001). Conversely, a significantly higher risk of OGID and fibromyalgia was found in G1 (1.56 95% CI 1.06-2.33; 1.69 95% CI 1.05-2.68, respectively) and G2 (1.91 95% CI 1.05-3.24; 2.13 95% CI 1.14-3.41, respectively) vs. G0. No treatment risk reduction was observed in haematological malignancies, cardiovascular events and endocrinological comorbidities. CONCLUSIONS: Overall, our study confirms the safety of TNFi and anti-IL in SpA patients, albeit with some caveats pertaining to solid cancers, OGID and fibromyalgia. Furthermore, taking into consideration causality with observational data may yield more reliable and relevant clinical information.

Patterns of Growth of Tumors in Li-Fraumeni Syndrome by Imaging: A Case Series.

Although tumors of Li-Fraumeni syndrome (LFS) have a premalignant or dormant phase that could be exploited by early imaging detection, this has been underevaluated in the literature. We present a case series of patients with LFS followed by imaging over time to highlight patterns of growth of tumors and hotspots of missed tumors in this population. Clinical and imaging features were available for 29 tumors of 24 carriers of a germline TP53 pathogenic variant, developed between 1999 and 2023 were retrospectively reviewed in a single tertiary pediatric center. Imaging characteristics of tumors were evaluated with MRI, CT, and radiographs. Local invasion, time interval for developing primary cancer, and/or recurrent disease and metastasis, and factors that delayed the tumor diagnosis were assessed. In patients with multiple tumors the median time intervals for development of first, second, and third primary cancers were 45.9, 79.8, and 28.1 months, respectively. Hotspots of missed tumors included superficial soft tissues, areas close to bones, on the scalp, in tissues around the adrenal region and in small hypodense lesions on brain CT. In conclusion, the pattern of growth of tumors is variable and erratic in LFS patients with some tumors presenting with a dormant pattern.

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.

Evaluating the Outcomes and Trainee Performance of a Canadian Medical Imaging Clinician Investigator Program.

Purpose: To measure the research productivity of trainees from the University of Toronto's Medical Imaging Clinician Investigator Program (MI-CIP) and comparing it with the research productivity of trainees from MI-non-CIP and General Surgery (GSx) Clinician Investigator Program. Methods: We identified residents who completed an MI-CIP, MI-non-CIP and GSx-CIP from 2006-2016. In each group of trainees, we assessed 3 research productivity outcomes with non-parametric tests before residency and at 7 years post-CIP completion/post-graduation. Research productivity outcomes include the number of total publications, the number of first-author publications, and the publication's average journal impact factor (IF). Results: We identified 11 MI-CIP trainees (male/female: 9 [82%]/2 [18%]), 74 MI-non-CIP trainees (46 [62%]/28 [38%]) and 41 GSx-CIP trainees (23 [56%]/18 [44%]). MI-CIP trainees had statistically significant higher research productivity than MI-non-CIP in all measured outcomes. The median (interquartile range, IQR) number of total publications of MI-CIP vs MI-non-CIP trainees was 5.0 (8.0) vs 1.0 (2.0) before residency and 6.0 (10.0) vs .0 (2.0) at 7 years post-CIP completion/post-graduation. The median (IQR) first-author publications of MI-CIP vs MI-non-CIP trainees was 2.0 (3.0) vs .0 (1.0) before residency and 2.0 (4.0) vs (.0) (1.0) at 7 years post-CIP completion/post-graduation. The median (IQR) average journal IF of MI-CIP vs MI-non-CIP trainees was 3.2 (2.0) vs .3 (2.4) before residency and 3.9 (3.2) vs .0 (2.6) at 7 years post-CIP completion/post-graduation. Between MI-CIP and GSx-CIP trainees, there were no significant differences in research productivity in all measured outcomes. Conclusion: MI-CIP trainees actively conducted research after graduation. These trainees demonstrated early research engagement before residency. The similar research productivity of MI-CIP vs GSx-CIP trainees shows initial success of MI-CIP trainees.

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.