Do fatty lesions explain the effect of inflammation on new syndesmophytes in patients with radiographic axial spondyloarthritis? Results from the SIAS cohort and ASSERT trial

OBJECTIVES: To determine how much of the effect of vertebral corner inflammation on development of syndesmophytes is explained by vertebral corner fat deposition. METHODS: Patients with radiographic axial spondyloarthritis (r-axSpA) from the SIAS (Sensitive Imaging in Ankylosing Spondylitis) cohort and ASSERT (Ankylosing Spondylitis Study for the Evaluation of Recombinant Infliximab Therapy) trial were assessed at T0, T1 (SIAS: 1 year; ASSERT: 24 weeks) and T2 (2 years). Syndesmophytes assessed in each vertebral corner by whole spine low-dose CT (SIAS) or spinal radiographs (ASSERT) at T0 and T2 were considered present if seen by two of two readers. Inflammation (T0) and fat deposition (T0 and T1) on MRI were present if seen by ≥2 of 3 readers (SIAS) or 2 of 2 readers (ASSERT). Vertebral corners showing fat deposition or a syndesmophyte at baseline were ignored. Mediation analysis was applied to determine what proportion of the total effect of inflammation on syndesmophyte formation could be explained via the path of intermediate fat deposition. RESULTS: Forty-nine SIAS patients (with 2667 vertebral corners) and 168 ASSERT patients (with 2918 vertebral corners) were analysed. The presence of inflammation at T0 increased the probability of a new syndesmophyte in the same vertebral corner at T2 by 9.3%. Of this total effect, 0.2% (2% (0.2 of 9.3) of the total effect) went via intermediate new fat deposition. In ASSERT, the total effect was 7.3%, of which 0.8% (10% of the total effect) went via new fat deposition. CONCLUSION: In r-axSpA, vertebral corner inflammation may lead to syndesmophyte formation but in a minority of cases via visible fat deposition

Single-case Design Studies in Children with Cerebral Palsy:A Scoping Review

Aim: To critically evaluate single-case design (SCD) studies performed within the population of children/adolescents with cerebral palsy (CP). Methods: A scoping review of SCD studies of children/adolescents with CP. Demographic, methodological, and statistical data were extracted. Articles were evaluated using the Risk of Bias in N-of-1 Trials (RoBiNT) Scale and the Consolidated Standards of Reporting Trials (CONSORT) extension for N-of-1 trials (CENT 2015). Comments regarding strengths and limitations were analyzed. Results: Studies investigated the effects of a wide range of interventions on various outcomes. Most SCD types were adopted in multiple studies. All studies used visual inspection rather than visual analysis, often complemented with basic statistical descriptives. Risk of bias was high, particularly concerning internal validity. Many CENT items were insufficiently reported. Several benefits and limitations of SCD were identified. Conclusions: The quality of evidence from results of SCD studies needs to be increased through risk of bias reduction

Role of vertebral corner inflammation and fat deposition on MRI on syndesmophyte development detected on whole spine low-dose CT scan in radiographic axial spondyloarthritis

Objectives To investigate the associations between MRI detected vertebral corner inflammation (VCI) and vertebral corner fat deposition (VCFD) on whole spine low-dose CT scan (ldCT) detected syndesmophyte formation and growth. Methods Patients from the Sensitive Imaging in Ankylosing Spondylitis cohort underwent MRI (baseline, 1 year and 2 years) and ldCT (baseline and 2 years). MR images were scored by three readers for VCI and VCFD, MRI patterns were defined by presence of VCI and/or VCFD over 2 years. LdCT images were scored by two central readers for presence and size of syndesmophytes and change was calculated for new or new/grown syndesmophytes. Multilevel generalised estimated equations were used to test the associations between VCI and VCFD and syndesmophyte development. Results Fifty radiographic patients with axial spondyloarthritis were included (mean age 49 years, 86% male, 78% HLA-B27+). Absence of both VCI and VCFD protected against syndesmophyte development (ORs 0.36-0.37). Presence of VCI and/or VCFD increased the risk of syndesmophyte development (ORs 1.73-2.60). Out of all corners with a new or new/grown syndesmophyte, 47% of corners according to reader 1 and 44% according to reader 2 had neither VCI nor VCFD preceding the bone formation. Conclusions VCI and VCFD were positively associated with syndesmophyte development. This has been shown for the first time for syndesmophytes detected on ldCT and also in the thoracic spine. However, almost half of all bone formation occurred in corners without VCI or VCFD, suggesting the presence of these lesions in yearly MRIs does not fully clarify the development of syndesmophytes

Role of vertebral corner inflammation and fat deposition on MRI on syndesmophyte development detected on whole spine low-dose CT scan in radiographic axial spondyloarthritis

Publisher Copyright: © Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.OBJECTIVES: To investigate the associations between MRI detected vertebral corner inflammation (VCI) and vertebral corner fat deposition (VCFD) on whole spine low-dose CT scan (ldCT) detected syndesmophyte formation and growth. METHODS: Patients from the Sensitive Imaging in Ankylosing Spondylitis cohort underwent MRI (baseline, 1 year and 2 years) and ldCT (baseline and 2 years). MR images were scored by three readers for VCI and VCFD, MRI patterns were defined by presence of VCI and/or VCFD over 2 years. LdCT images were scored by two central readers for presence and size of syndesmophytes and change was calculated for new or new/grown syndesmophytes. Multilevel generalised estimated equations were used to test the associations between VCI and VCFD and syndesmophyte development. RESULTS: Fifty radiographic patients with axial spondyloarthritis were included (mean age 49 years, 86% male, 78% HLA-B27+). Absence of both VCI and VCFD protected against syndesmophyte development (ORs 0.36-0.37). Presence of VCI and/or VCFD increased the risk of syndesmophyte development (ORs 1.73-2.60). Out of all corners with a new or new/grown syndesmophyte, 47% of corners according to reader 1 and 44% according to reader 2 had neither VCI nor VCFD preceding the bone formation. CONCLUSIONS: VCI and VCFD were positively associated with syndesmophyte development. This has been shown for the first time for syndesmophytes detected on ldCT and also in the thoracic spine. However, almost half of all bone formation occurred in corners without VCI or VCFD, suggesting the presence of these lesions in yearly MRIs does not fully clarify the development of syndesmophytes.publishersversionpublishe

Associations between syndesmophytes and facet joint ankylosis in radiographic axial spondyloarthritis patients on low-dose CT over 2 years

OBJECTIVES: In radiographic axial spondyloarthritis (r-axSpA), spinal damage manifests as syndesmophytes and facet joint ankylosis (FJA). We evaluated whether the presence of one lesion increased the risk of the other lesion. METHODS: Patients with r-axSpA underwent low-dose CT (ldCT) and MRI of the whole spine at baseline and 2 years. On ldCT, vertebrae were scored for presence and size of syndesmophytes; facet joints were assessed for ankylosis. MR images were assessed for inflammation. Two hypotheses were tested: (i) presence of FJA is associated with new syndesmophyte(s) on the same vertebral unit (VU) 2 years later, and (ii) presence of bridging syndesmophyte(s) is associated with new FJA on the same VU 2 years later. Two generalized estimating equations models were tested per hypothesis using increase of FJA/syndesmophytes (model A) or presence of FJA/syndesmophytes (model B) as outcome, adjusted for inflammation at baseline. Secondary analyses tested the hypotheses with outcomes on adjacent VUs and dose-response effects. RESULTS: Fifty-one patients were included (mean age 49, 84% male, 82% HLA-B27+). Baseline bridging syndesmophytes occurred more often (range: 10-60% per VU) than FJA (range: 8-36%). Odds ratios (ORs) (95% CI) for presence of bridging syndesmophytes on development of FJA were 3.55 (2.03, 6.21) for model A and 3.30 (2.14, 5.09) for model B. ORs for presence of baseline FJA on new syndesmophytes were 1.87 (1.20, 2.92) for model A and 1.69 (0.88, 3.22) for model B. Secondary analyses yielded positive ORs for both hypotheses. CONCLUSIONS: Bone formation in vertebrae and in facet joints influence each other's occurrence, with the effect of syndesmophytes being larger than that of FJA