Management of pregnancy in autoimmune rheumatic diseases: maternal disease course, gestational and neonatal outcomes and use of medications in the prospectiveItalian P-RHEUM.it study.

OBJECTIVES: To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it. METHODS: Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018-2023). Maternal and infant information were collected in a web-based database. RESULTS: We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress. CONCLUSIONS: Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.

Reliability assessment of the OMERACT whole-body magnetic resonance imaging scoring system for juvenile idiopathic arthritis.

Inter-reader reliability of a new scoring system for evaluating joint inflammation and enthesitis in whole body MRI (WBMRI) in juvenile idiopathic arthritis was tested. The scoring system grades 732 item-region combinations of bone marrow and soft tissue changes for commonly involved joints and entheseal sites. Five radiologists rated 17 WBMRI scans through an online rating platform. Item-wise reliability was calculated for 117 items with non-zero scores in >10 % of readings. Interquartile ranges of the five-reader Kappa reliability coefficients were 0.58-0.73 (range: 0.36-0.88) for the joints, 0.65-0.81 (range: 0.39-0.95) for the entheses, and 0.62-0.75 (range: 0.60-0.76) for chronic nonbacterial osteomyelitis-like lesions.

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.

Cutting-Edge Strategies for Renal Tumour-like Lesions in Granulomatosis with Polyangiitis: A Systematic Review.

BACKGROUND: Granulomatosis with polyangiitis (GPA) is characterised by granulomatous inflammation and small-to-medium vessel necrotising vasculitis, mainly affecting respiratory tract and kidneys. Renal involvement presenting as tumour-like lesions poses diagnostic and treatment challenges. METHODS: Following the observation of a GPA patient presenting with multiple renal tumour-like lesions, we conducted a systematic literature review on MEDLINE/PubMed, EMBASE, and Cochrane databases. Data gathered from the literature were analysed to summarise the diagnostic approach, management, and outcome of renal GPA-related tumour-like lesions. RESULTS: a 49-year-old female presented with persistent constitutional symptoms and multiple bilateral renal lesions. Renal biopsy showed chronic interstitial inflammation with necrotising granulomas. Laboratory tests disclosed positive anti-proteinase 3 (PR3) anti-neutrophil cytoplasmic antibody (ANCA) leading to a final diagnosis of GPA. She was effectively treated with high-dose glucocorticoids and rituximab. Literature search yielded 41 articles, concerning 42 GPA patients with renal masses, presenting bilaterally in 23.8% of the cases. Positive PR3-ANCA was observed in 86.5% of the cases. Half of 42 patients showed kidney abnormalities. Treatment with glucocorticoids (83.3%) and immunosuppressive agents (80.9%) resulted in an overall good remission rate and favourable prognosis. CONCLUSIONS: GPA should be considered in the differential diagnoses of kidney tumour-like lesions. The diagnosis is challenging, and histological examination greatly contributes to the diagnostic work-up.

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.

Defining domains: developing consensus-based definitions for foundational domains in OMERACT core outcome sets.

OBJECTIVE: To develop a set of detailed definitions for foundational domains commonly used in OMERACT (Outcome Measures in Rheumatology) core domain sets. METHODS: We identified candidate domain definitions from prior OMERACT publications and websites and publications of major organizations involved in outcomes research for six domains commonly used in OMERACT Core Domain Sets: pain intensity, pain interference, physical function, fatigue, patient global assessment, and health-related quality of life. We conducted a two-round survey of OMERACT working groups, patient research partners, and then the OMERACT Technical Advisory Group to establish their preferred domain definitions. Results were presented at the OMERACT 2023 Methodology Workshop, where participants discussed their relevant lived experience and identified potential sources of variability giving the needed detail in our domain definitions. RESULTS: One-hundred four people responded to both rounds of the survey, and a preferred definition was established for each of the domains except for patient global assessment for which no agreement was reached. Seventy-five participants at the OMERACT 2023 Methodology Workshop provided lived experience examples, which were used to contextualise domain definition reports for each of the five domains. CONCLUSION: Using a consensus-based approach, we have created a detailed definition for five of the foundational domains in OMERACT core domain sets; patient global assessment requires further research. These definitions, although not mandatory for working groups to use, may facilitate the initial domain-match assessment step of instrument selection, and reduce the time and resources required by future OMERACT groups when developing core outcome sets.

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.

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.

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.

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.

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.

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.

Innovative cellular therapies for autoimmune diseases: expert-based position statement and clinical practice recommendations from the EBMT practice harmonization and guidelines committee.

Autoimmune diseases (ADs) are characterized by loss of immune tolerance, high chronicity, with substantial morbidity and mortality, despite conventional immunosuppression (IS) or targeted disease modifying therapies (DMTs), which usually require repeated administration. Recently, novel cellular therapies (CT), including mesenchymal stromal cells (MSC), Chimeric Antigen Receptors T cells (CART) and regulatory T cells (Tregs), have been successfully adopted in ADs. An international expert panel of the European Society for Blood and Marrow Transplantation and the International Society for the Cell and Gene Therapy, reviewed all available evidence, based on the current literature and expert practices, on use of MSC, CART and Tregs, in AD patients with rheumatological, neurological, and gastroenterological indications. Expert-based consensus and recommendations for best practice and quality of patient care were developed to support clinicians, scientists, and their multidisciplinary teams, as well as patients and care providers and will be regularly updated.

Characterization and quantification of fluid in the abdomen by ultrasound and magnetic resonance imaging in children with clinical suspicion of appendicitis.

PURPOSE: While regarded as a secondary sign of pediatric appendicitis, the frequency of physiologic intra-abdominal fluid in children with suspected but absent appendicitis is unknown. Ex vivo: to assess the validity of US/MRI measurements of free fluid. In vivo: in suspected pediatric appendicitis, to assess the amount of abdominal fluid by US and MRI, determine performance characteristics of US in fluid detection and identify fluid volume ranges in confirmed appendicitis. METHODS: Ex vivo: criterion validity of US and MRI for fluid volume measurements was tested using tissue-mimicking phantoms filled with different volumes of distilled water. In vivo: all participants from a previous prospective study of suspected appendicitis were evaluated by US; MRI was performed after equivocal USs. Qualitative and quantitative analyses of abdominal fluid and correlation of fluid presence with appendicitis were performed. RESULTS: Ex vivo: no difference was found between phantom-fluid amount and measured volume using the formula for volume of an ellipsoid for US (P=0.19) or MRI (P=0.08). In vivo: intra-abdominal fluid was present in 212/591 (35.9%) patients; 75/212 patients with fluid (35.4%) had appendicitis, 60 (28.3%) had alternate diagnoses, and 77 (36.3%) had physiologic fluid. Sensitivity and specificity of US for fluid detection were 84% (95% CI 71-93) and 65% (95% CI 52-77), respectively. In children with versus without appendicitis, the respective ranges of fluid volume were 0.7-1148.8 ml and 0.8-318 ml. CONCLUSION: The volume of an ellipsoid formula is a valid method for quantifying intra-abdominal fluid. The sole presence of intra-abdominal fluid on US does not support the diagnosis of pediatric appendicitis.

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 (AEs) 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.

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.

Systematic calibration reduces sources of variability for the preliminary OMERACT juvenile idiopathic arthritis MRI- sacroiliac joint score (OMERACT JAMRIS-SIJ).

OBJECTIVE: To determine whether systematic calibration enhances scoring proficiency of the OMERACT juvenile idiopathic arthritis MRI-Sacroiliac Joint score (JAMRIS-SIJ) and whether contrast-enhancement enhances its performance. METHODS: MRI SIJ scans of 50 cases with juvenile spondyloarthritis were scored by 7 raters after calibration with 3 different knowledge transfer tools. RESULTS: Calibrated readers achieved greater reliability for scoring certain inflammatory and structural lesions. Sensitivity and reliability for scoring inflammatory lesions was greater on fluid-sensitive compared to contrast-enhanced sequences. CONCLUSION: Systematic calibration should be implemented prior to the use of JAMRIS-SIJ for clinical trials. It is unlikely that contrast-enhanced MRI will improve the performance of this method.

Early Cancer Detection in Li-Fraumeni Syndrome with Cell-Free DNA.

People with Li-Fraumeni syndrome (LFS) harbor a germline pathogenic variant in the TP53 tumor suppressor gene, face a near 100% lifetime risk of cancer, and routinely undergo intensive surveillance protocols. Liquid biopsy has become an attractive tool for a range of clinical applications, including early cancer detection. Here, we provide a proof-of-principle for a multimodal liquid biopsy assay that integrates a targeted gene panel, shallow whole-genome, and cell-free methylated DNA immunoprecipitation sequencing for the early detection of cancer in a longitudinal cohort of 89 LFS patients. Multimodal analysis increased our detection rate in patients with an active cancer diagnosis over uni-modal analysis and was able to detect cancer-associated signal(s) in carriers prior to diagnosis with conventional screening (positive predictive value = 67.6%, negative predictive value = 96.5%). Although adoption of liquid biopsy into current surveillance will require further clinical validation, this study provides a framework for individuals with LFS. SIGNIFICANCE: By utilizing an integrated cell-free DNA approach, liquid biopsy shows earlier detection of cancer in patients with LFS compared with current clinical surveillance methods such as imaging. Liquid biopsy provides improved accessibility and sensitivity, complementing current clinical surveillance methods to provide better care for these patients. See related commentary by Latham et al., p. 23. This article is featured in Selected Articles from This Issue, p. 5.

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.