Development of the 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria, Phase III-D Report: Multi Criteria Decision Analysis.

BACKGROUND: The 2023 ACR/EULAR Antiphospholipid Syndrome (APS) Classification Criteria development, aiming to identify patients with high likelihood of APS for research, employed a four-phase methodology. Phase I and II resulted in 27 proposed candidate criteria, organized into laboratory and clinical domains. Here, we summarize the last stage of Phase III efforts employing a consensus-based multi-criteria decision analysis (MCDA) to weigh candidate criteria and identify an APS classification threshold score. METHODS: We evaluated 192 unique, international real-world cases referred for "suspected APS" with a wide range of APS manifestations. Using proposed candidate criteria, subcommittee members rank-ordered 20 representative cases from highly unlikely to highly likely APS. During an in-person meeting, the subcommittee refined definitions and participated in an MCDA exercise to identify relative weights of candidate criteria. Using consensus decisions and pairwise criteria comparisons, 1000Minds™ software assigned criteria weights, and we rank ordered 192 cases by their additive scores. A consensus-based threshold score for APS classification was set. RESULTS: Pre-meeting evaluation of 20 representative cases demonstrated variability in APS assessment. MCDA resolved 81 pairwise decisions; relative weights identified domain item hierarchy. After assessing 192 cases by weights and additive scores, the Steering Committee reached consensus that APS classification should require separate clinical and laboratory scores, rather than a single aggregate score, to ensure high specificity. CONCLUSION: Using MCDA, candidate criteria preliminary weights were determined. Unlike other disease classification systems using a single aggregate threshold score, separate clinical and laboratory domain thresholds were incorporated into the new APS classification criteria.

Classification Criteria for Axial Disease in Youth with Juvenile Spondyloarthritis.

OBJECTIVES: To develop and validate classification criteria for axial disease in youth with juvenile spondyloarthritis (SpA; AxJSpA). METHODS: This international initiative consisted of four phases: 1) Item generation; 2) Item reduction; 3) Criteria development; and 4) Validation of the AxJSpA criteria by an independent team of experts in an internationally representative Validation cohort. RESULTS: These criteria are intended to be used on youth with a physician diagnosis of juvenile SpA and for whom axial disease is suspected. Item generation consisted of a systematic literature review and a free-listing exercise using input from international physicians and collectively resulted in 108 items. After the item reduction exercise and expert panel input, 37 items remained for further consideration. The final AxJSpA criteria domains included: imaging: active inflammation, imaging: structural lesions, pain chronicity, pain pattern, pain location, stiffness, and genetics. The most heavily weighted domains were active inflammation and structural lesions on imaging. Imaging typical of sacroiliitis was deemed necessary, but not sufficient, to classify a youth with AxJSpA. The threshold for classification of AxJSpA was a score of ≥55 (out of 100). When tested in the validation data set, the final criteria had a specificity of 97.5% (95% CI: 91.4-99.7), sensitivity of 64.3% (95% CI: 54.9-73.1) and Area Under the Receiver Operating Characteristic (AUROC) curve of 0.81 (95% CI: 0.76-0.86). CONCLUSIONS: The new AxJSpA classification criteria require an entry criterion, physician diagnosis of juvenile SpA, and include seven weighted domains. The AxJSpA classification criteria are validated and designed to identify participants for research studies.

The 2023 ACR/EULAR Antiphospholipid Syndrome Classification Criteria.

OBJECTIVE: To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR. METHODS: This international multidisciplinary initiative included 4 phases: 1) Phase I, criteria generation by surveys and literature review; 2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; 3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and 4) Phase IV, validation using independent adjudicators' consensus as the gold standard. RESULTS: The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into 6 clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and 2 laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-ß2 -glycoprotein I antibodies). Patients accumulating at least 3 points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria versus the 2006 revised Sapporo classification criteria had a specificity of 99% versus 86%, and a sensitivity of 84% versus 99%. CONCLUSION: These new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk-stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research.

2023 ACR/EULAR antiphospholipid syndrome classification criteria.

OBJECTIVE: To develop new antiphospholipid syndrome (APS) classification criteria with high specificity for use in observational studies and trials, jointly supported by the American College of Rheumatology (ACR) and EULAR. METHODS: This international multidisciplinary initiative included four phases: (1) Phase I, criteria generation by surveys and literature review; (2) Phase II, criteria reduction by modified Delphi and nominal group technique exercises; (3) Phase III, criteria definition, further reduction with the guidance of real-world patient scenarios, and weighting via consensus-based multicriteria decision analysis, and threshold identification; and (4) Phase IV, validation using independent adjudicators' consensus as the gold standard. RESULTS: The 2023 ACR/EULAR APS classification criteria include an entry criterion of at least one positive antiphospholipid antibody (aPL) test within 3 years of identification of an aPL-associated clinical criterion, followed by additive weighted criteria (score range 1-7 points each) clustered into six clinical domains (macrovascular venous thromboembolism, macrovascular arterial thrombosis, microvascular, obstetric, cardiac valve, and hematologic) and two laboratory domains (lupus anticoagulant functional coagulation assays, and solid-phase enzyme-linked immunosorbent assays for IgG/IgM anticardiolipin and/or IgG/IgM anti-ß2-glycoprotein I antibodies). Patients accumulating at least three points each from the clinical and laboratory domains are classified as having APS. In the validation cohort, the new APS criteria vs the 2006 revised Sapporo classification criteria had a specificity of 99% vs 86%, and a sensitivity of 84% vs 99%. CONCLUSION: These new ACR/EULAR APS classification criteria were developed using rigorous methodology with multidisciplinary international input. Hierarchically clustered, weighted, and risk-stratified criteria reflect the current thinking about APS, providing high specificity and a strong foundation for future APS research.

Consensus-Driven Definition for Unequivocal Sacroiliitis on Radiographs in Juvenile Spondyloarthritis.

OBJECTIVE: Radiography is still used worldwide for the detection of sacroiliitis in juvenile spondyloarthritis (JSpA), despite its low sensitivity and reliability. We aimed to define unequivocal evidence of sacroiliitis on pelvic radiography in skeletally immature youth for use in classification criteria when magnetic resonance imaging (MRI) is unavailable. METHODS: Subjects were a retrospective cohort of juvenile patients with spondyloarthritis with a radiograph and MRI as part of a diagnostic evaluation for axial disease. Six musculoskeletal imaging experts underwent an iterative consensus process to define unequivocal sacroiliitis on radiography in skeletally immature youth. Radiographs were graded using the modified New York (mNY) criteria and the unequivocal sacroiliitis criteria. Interrater agreement was assessed with the Fleiss [Formula: see text] statistic. Specificity, area under the receiver operator characteristic curve (AUROC), and sensitivity of the 2 measures were tested using 2 MRI reference standards. RESULTS: A total of 112 subjects, with a median age of 14.9 (range 6.7-20.1) years, were included. The Fleiss [Formula: see text] was fair for the mNY criteria (0.54, 95% CI 0.42-0.67) and the unequivocal sacroiliitis criteria (0.58, 95% CI 0.46-0.69). The unequivocal sacroiliitis criteria achieved > 90% specificity using both MRI reference standards. Sensitivity (59.26 and 57.14 vs 44.83 and 43.33) and AUROC (0.76 and 0.76 vs 0.71 and 0.71) were higher, for both reference standards, for the unequivocal sacroiliitis in youth definition than for the mNY criteria, respectively. CONCLUSION: In this study, we propose the first consensus-derived definition to our knowledge of unequivocal sacroiliitis by radiography in skeletally immature youth. This definition achieved excellent specificity and had higher AUROC and sensitivity values than the mNY criteria using both MRI reference standards. This definition has applicability to the JSpA axial disease classification imaging criterion when MRI is unavailable.

Data-Driven Magnetic Resonance Imaging Definitions for Active and Structural Sacroiliac Joint Lesions in Juvenile Spondyloarthritis Typical of Axial Disease: A Cross-Sectional International Study.

OBJECTIVE: We aimed to determine quantitative sacroiliac (SI) joint magnetic resonance imaging (MRI) cutoffs for active and structural lesions that will be incorporated as imaging domains in classification criteria of axial disease in juvenile spondyloarthritis (SpA). METHODS: MRI scans from an international cross-section of juvenile SpA patients were reviewed by 6 musculoskeletal imaging experts blinded to clinical details. Raters globally assessed the presence/absence of lesions typical of axial SpA and performed SI joint quadrant- or joint-based scoring. Sensitivity and specificity of lesion cutoffs were calculated using a rater majority (≥4 of 6 raters) on a global assessment of the presence/absence of active or structural lesions typical of axial SpA with high confidence as the reference standard. Cutoffs were validated in an independent cohort. RESULTS: Imaging from 243 subjects, 61% male, median age 14.9 years, had sequences available for detailed MRI scoring. Optimal cutoffs for defining lesions typical of axial disease in juvenile SpA were: 1) inflammatory lesion: bone marrow edema in ≥3 SI joint quadrants across all SI joint MRI slices (sensitivity 98.6%, specificity 96.5%); 2) structural lesions: erosion in ≥3 quadrants or sclerosis or fat lesion in ≥2 SI joint quadrants or backfill or ankylosis in ≥2 joint halves across all SI joint MRI slices (sensitivity 98.6%, specificity 95.5%). Sensitivity and specificity of the optimal cutoffs in the validation cohort were excellent. CONCLUSION: We propose data-driven cutoffs for active inflammatory and structural lesions on MRI typical of axial disease in juvenile SpA that have high specificity and sensitivity using central imaging global assessment as the reference standard and excellent reliability.

First source-to-sink monitoring shows dense head controls sediment flux and runout in turbidity currents.

Until recently, despite being one of the most important sediment transport phenomena on Earth, few direct measurements of turbidity currents existed. Consequently, their structure and evolution were poorly understood, particularly whether they are dense or dilute. Here, we analyze the largest number of turbidity currents monitored to date from source to sink. We show sediment transport and internal flow characteristic evolution as they runout. Observed frontal regions (heads) are fast (>1.5 m/s), thin (<10 m), dense (depth averaged concentrations up to 38%vol), strongly stratified, and dominated by grain-to-grain interactions, or slower (<1 m/s), dilute (<0.01%vol), and well mixed with turbulence supporting sediment. Between these end-members, a transitional flow head exists. Flow bodies are typically thick, slow, dilute, and well mixed. Flows with dense heads stretch and bulk up with dense heads transporting up to 1000 times more sediment than the dilute body. Dense heads can therefore control turbidity current sediment transport and runout into the deep sea.