Objective To compare immune cell phenotype and function in psoriatic arthritis (PsA) versus psoriasis in order to better understand the pathogenesis of PsA. Methods In‐depth immunophenotyping of different T cell and dendritic cell subsets was performed in patients with PsA, psoriasis, or axial spondyloarthritis and healthy controls. Subsequently, we analyzed cells from peripheral blood, synovial fluid (SF), and skin biopsy specimens using flow cytometry, along with high‐throughput transcriptome analyses and functional assays on the specific cell populations that appeared to differentiate PsA from psoriasis. Results Compared to healthy controls, the peripheral blood of patients with PsA was characterized by an increase in regulatory CD4+ T cells and interleukin‐17A (IL‐17A) and IL‐22 coproducing CD8+ T cells. One population specifically differentiated PsA from psoriasis: i.e., CD8+CCR10+ T cells were enriched in PsA. CD8+CCR10+ T cells expressed high levels of DNAX accessory molecule 1 and were effector memory cells that coexpressed skin‐homing receptors CCR4 and cutaneous lymphocyte antigen. CD8+CCR10+ T cells were detected under inflammatory and homeostatic conditions in skin, but were not enriched in SF. Gene profiling further revealed that CD8+CCR10+ T cells expressed GATA3, FOXP3, and core transcriptional signature of tissue‐resident memory T cells, including CD103. Specific genes, including RORC, IFNAR1, and ERAP1, were up‐regulated in PsA compared to psoriasis. CD8+CCR10+ T cells were endowed with a Tc2/22‐like cytokine profile, lacked cytotoxic potential, and displayed overall regulatory function. Conclusion Tissue‐resident memory CD8+ T cells derived from the skin are enhanced in the circulation of patients with PsA compared to patients with psoriasis alone. This may indicate that aberrances in cutaneous tissue homeostasis contribute to arthritis development.

Pooled results of Austin-Kartush studies showed that in patients with COM, with or without cholesteatoma, the malleus status is a significant predictor of postoperative hearing outcome, independent of the stapes condition. Studies reporting on individual ossicle status supported this finding by showing that only malleus condition influenced postoperative hearing outcome. These findings are based on level IV evidence, which indicates the need for future high-level evidence studies.

BackgroundAltered sensory sensitivity is generally linked to seizure-susceptibility in childhood epilepsy but may also be associated to the highly prevalent problems in behavioral adaptation. This association is further suggested by the frequent overlap of childhood epilepsy with autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD), conditions in which altered behavioral responses to sensory stimuli have been firmly established. A continuum of sensory processing defects due to imbalanced neuronal inhibition and excitation across these disorders has been hypothesizedthat may lead to common symptoms of inadequate modulation of behavioral responses to sensory stimuli. Here, we investigated the prevalence of sensory modulation disorders among children with epilepsy and their relation with symptomatology of neurodevelopmental disorders.MethodsWe used the Sensory Profile questionnaire to assess behavioral responses to sensory stimuli and categorize sensory modulation disorders in children with active epilepsy (aged 4–17 years). We related these outcomes to epilepsy characteristics and tested their association with comorbid symptoms of ASD (Social Responsiveness Scale) and ADHD (Strengths and Difficulties Questionnaire).ResultsSensory modulation disorders were reported in 49 % of the 158 children. Children with epilepsy reported increased behavioral responses associated with sensory “sensitivity,” “sensory avoidance,” and “poor registration” but not “sensory seeking.” Comorbidity of ASD and ADHD was associated with more severe sensory modulation problems, although 27 % of typically developing children with epilepsy also reported a sensory modulation disorder.ConclusionsSensory modulation disorders are an under-recognized problem in children with epilepsy. The extent of the modulation difficulties indicates a substantial burden on daily functioning and may explain an important part of the behavioral distress associated with childhood epilepsy.

ObjectiveTo compare the Heel Enthesitis MRI Scoring model (HEMRIS) with clinical and PET/CT outcomes in patients with cutaneous psoriasis (Pso), psoriatic arthritis (PsA) or ankylosing spondylitis (AS).MethodsThis prospective, observational study included 38 patients with Pso, PsA and AS. Patients were included regardless of presence or absence of clinical heel enthesitis. MRI-scans of both ankles and a whole-body 18F-FDG PET/CT were acquired. MRIs were assessed for enthesitis by two independent and blinded observers according to the HEMRIS. A physician, blinded for imaging results, performed clinical evaluations of enthesitis at the Achilles tendon and plantar fascia.ResultsIn total, 146 entheses were scored according to the HEMRIS and clinically assessed for enthesitis (6 entheses were clinically affected). In Achilles tendons with clinical enthesitis, the HEMRIS structural damage score was significantly higher, compared to Achilles tendons without clinical enthesitis (respective median scores 1.0 and 0.5; p=0.04). In clinically unaffected entheses, HEMRIS abnormalities occurred in 44/70 (63%) of Achilles tendons and in 23/70 (33%) of plantar fascia. At the Achilles tendon, local metabolic activity measured on PET/CT was weakly associated with the structural (rs=0.25, p=0.03) and total HEMRIS (rs=0.26, p=0.03).ConclusionThis study revealed a high prevalence of subclinical HEMRIS abnormalities and discrepancy between HEMRIS and clinical and PET/CT findings. This may suggest that the HEMRIS is a sensitive method for detection of inflammatory and structural disease of enthesitis at the Achilles tendon and plantar fascia, although the clinical significance of these MRI findings remains to be determined in longitudinal studies.

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Background: Based on the unique physical properties of collagen, dualenergy computed tomography (DECT) is able to detect pathological changes in fibrous structures. This has been demonstrated for the Achilles tendon (1) and traumatic disc injury in elderly patients (2). Objectives: The purpose of this study was to assess the diagnostic potential of DECT collagen imaging for the detection of intervertebral disc involvement in patients with axial spondyloarthritis (axSpA) in correlation with osseous lesions in MRI. Methods: Sixteen patients with suspicion of or known axSpA and back pain were included. All patients underwent a 1.5-Tesla-MRI including T1 and STIR sequences and an ultra-low-dose DECT of the spine using two sequential helical acquisitions. DECT images were reconstructed in 120 kV-equivalent standard CT images and collagen maps with 1.0 mm slice thickness in sagittal reconstructions. MRI and CT images (D1 to S1) were scored for transdiscal ankylosis, Andersson lesions, syndesmophytes, spondylitis anterior and fatty corner lesions (when applicable) as well as for degenerative findings. DECT images were scored for a loss of collagen density affecting the nucleus pulposus or the anulus fibrosus. Sensitivity (SE) and specificity (SP) values were calculated. All analyses were performed on the level of the disco vertebral units. Results: Twelve male and four female patients with a mean age of 46.6 ± 11.6 years were included. Eleven were finally diagnosed with axSpA, 3 with degenerative spine disease and 2 with diffuse idiopathic skeletal hyperostosis (DISH). MRI detected 73 lesions in 274 discovertebral units (61 SpA related, 12 degenerative; 26 affecting the disc and 35 affecting the vertebral corner) and CT 68, whereas DECT identified pathologically decreased collagen content in 60 discs (35 in the nucleus and 25 in the anulus). DECT showed high diagnostic accuracy when compared to SpArelated and degenerative changes (MRI and CT combined; SE: 67%; SP 99.5%) and for SpA-lesions only (SE 72%; SP 94.2%), however, was less susceptible for degeneration (SE 60%; SP 81.9%). When comparing disc lesions in SpA as detected by MRI (transdiscal ankylosis and Andersson lesions) with nucleus-pulposus changes in DECT, it showed an SE of 88.5% and an SP of 95.1%. However, the diagnostic accuracy was inferior when comparing anterior spondylitis and fatty corner lesions in MRI with anulus fibrosus changes in DECT (SE 51.4% and SP 97%), although the SE was markedly higher for active inflammatory corner lesion (92.3%) than for fatty marrow lesions (23.3%). The mean radiation exposure was 8.1 ± 3.4 mSv. Conclusion: DECT is able to demonstrate soft-tissue involvement of the disc, especially for transdiscal ankylosis, Andersson lesions and active anterior spondylitis. This can be achieved with considerably low radiation exposure. While measuring the collagen density, it provides additional information to conventional CT and MR images. Thus, it has high potential to develop into a useful tool to further enhance our understanding o...

IntroductionPsoriatic arthritis (PsA) is a chronic, inflammatory, musculoskeletal disease that affects up to 30% of patients with psoriasis. Current challenges in clinical care and research include personalised treatment, understanding the divergence of therapy response and unravelling the multifactorial pathophysiology of this complex disease. Moreover, there is an urgent clinical need to predict, assess and understand the cellular and molecular pathways underlying the response to disease-modifying antirheumatic drugs (DMARDs). The TOFA-PREDICT clinical trial addresses this need. Our primary objective is to determine key immunological factors predicting tofacitinib efficacy and drug-free remission in PsA.Methods and analysisIn this investigator-initiated, phase III, multicentre, open-label, four-arm randomised controlled trial, we plan to integrate clinical, molecular and imaging parameters of 160 patients with PsA. DMARD-naïve patients are randomised to methotrexate or tofacitinib. Additionally, patients who are non-responsive to conventional synthetic (cs)DMARDs continue their current csDMARD and are randomised to etanercept or tofacitinib. This results in four arms each with 40 patients. Patients are followed for 1 year. Treatment response is defined as minimal disease activity at week 16. Clinical data, biosamples and images are collected at baseline, 4 weeks and 16 weeks; at treatment failure (treatment switch) and 52 weeks. For the first 80 patients, we will use a systems medicine approach to assess multiomics biomarkers and develop a prediction model for treatment response. Subsequently, data from the second 80 patients will be used for validation.Ethics and disseminationThe study was approved by the Medical Research Ethics Committee in Utrecht, Netherlands, is registered in the European Clinical Trials Database and is carried out in accordance with the Declaration of Helsinki. The study’s progress is monitored by Julius Clinical, a science-driven contract research organisation.Trial registration numberEudraCT: 2017-003900-28.

BackgroundPatients with psoriatic arthritis (PsA) have an increased risk of cardiovascular disease, possibly due to a chronic inflammatory state.ObjectivesThe main objective of this study was to investigate whether vascular inflammation, measured with 18-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT), is elevated in PsA patients.MethodsWe included 75 PsA patients with active peripheral arthritis (≥2 tender and swollen joints) from an ongoing clinical trial (EudraCT 2017-003900-28), and a retrospective group of 40 controls with melanoma, without distant metastases and not receiving immunotherapy. Both PsA patients and controls were aged 18-75 years. The main outcome measure was aortic vascular inflammation, which was measured using target-to-background-ratios (TBR) on PET/CT. Clinical disease activity in PsA was assessed with joint counts, body surface area and the composite measure Disease Activity index for PsA. Laboratory assessments included the inflammatory parameters C-reactive protein and Erythrocyte Sedimentation Rate. Vascular inflammation was compared between PsA patients and controls in univariate analysis with an unpaired t-test with equal variances. A multiple linear regression analysis was performed to adjust for age, gender, body mass index and mean arterial pressure (MAP). Associations of clinical parameters of disease activity in PsA with vascular inflammation were assessed using Spearman’s correlation coefficient.ResultsVascular inflammation was increased in PsA patients in comparison with controls (mean TBR for entire aorta respectively 1.53±0.15 and 1.42±0.13; P<0.001; Figure 1). This association remained significant after adjusting for gender, age, body mass index and mean arterial pressure (P=0.002). In individuals with PsA, vascular inflammation was not associated with disease-related parameters. There were no significant differences between PsA patients and controls regarding age, mean arterial pressure (MAP) and history of CVD. PsA patients had a higher BMI in comparison with healthy controls (Table 1).ConclusionAortic vascular inflammation was increased in patients with active PsA compared with controls. This evidence suggests that inflammation in PsA is not limited to skin and joints, but also involves the cardiovascular system.Table 1.Patients’ characteristicsCharacteristicaPsA (N=75)Controls (N=40)p-valueAge, years, median (IQR)53 (46-59)52 (42-59)0.353bMale sex43 (57.3)23 (57.5)1.000cBody Mass Index, kg/m2, mean±SD28.4±4.925.9±4.00.008dMean Arterial Pressure, mean±SD102.8±11.698.5±13.90.090dCurrent smoking10 (13.3)NAHistory of cardiovascular disease:HypertensionHyperlipidemiaDiabetesMyocardial infarctionCerebrovascular event12 (16.0)1 (1.3)2 (2.7)2 (2.7)06 (15.0)2 (5.0)001 (2.5)1.000c0.277c0.542c0.542c0.348cPsA duration, months, median (IQR)10.0 (1.0-123)NACurrent csDMARD use37 (49.3)NATJC (of 68 joints), median (IQR)4.0 (6.5-10.0)NASJC (of 66 joints), median (IQR)3.0 (5.0-9.0)NALEI count (1-6), median (IQR)0 (0.0-1.0)NABSA, median (IQR)1.0 (1.0-3.0)NACRP, median (IQR)1.0 (4.0-10.3)NALDL-cholesterol, mean±SD3.0±0.9NAaValues are expressed as n (%) unless stated otherwise.bMann-Whitney testcFisher’s exact testdIndependent Samples t-testAbbreviations. CRP = C-reactive protein, BSA = body surface area, LEI = Leeds Enthesits Index, DMARD = Disease Modifying Anti-Rheumatic Drugs, LEI = Leeds Enthesitis Index, LDL = low-density lipoprotein, NA= not available, PsA = psoriatic arthritis, SD = standard deviation, SJC = swollen joint count, TJC = tender joint countFigure 1.Increased vascular inflammation in the entire aorta and all separate aortic segments, assessed with the TBR, in PsA (n=75) in comparison with controls (n=40).***= P ≤ 0.001, **= P ≤ 0.01. Abbreviations: PsA = psoriatic arthritis.AcknowledgementsThis work was supported by Pfizer (New York, New York, USA). The collaboration project is cofunded by the PPP Allowance made available by Health~Holland, Top Sector Life Sciences & Health, to stimulate public–private partnerships (grant number: LSHM17074).The TOFA-PREDICT Author Group:A. van Tubergen,K. Hermans,M.E. Hettema,M.R. Kok,R.J. Bisoendial,A.W.R. van Kuijk,J. Wiegel,T.L.T.A. Jansen,A.C. Comarniceanu,L. Geurts – van Bon,L.G. Schipper,S.T.A. van Bijnen,S. Wijngaarden,A. Herman.Disclosure of InterestsNienke J. Kleinrensink: None declared, Wouter Foppen Grant/research support from: WF has received research grants from NovoNordisk and Pfizer which were paid to the institution., Negina Seddiqi: None declared, Harald Vonkeman Grant/research support from: Prof. H. Vonkeman reports having received grants, consulting fees or honorarium from AbbVie, Boehringer Ingelheim, Novartis, Pfizer, UCB, Janssen and Galapagos; all outside the submitted work., Karijn Suijkerbuijk Consultant of: Bristol-Myers Squibb, Merck Sharp and Dome, Abbvie, Pierre Fabre, Novartis, Sairopa. All paid to institution and outside the submitted work, Grant/research support from: Novartis, Roche, Merck Sharp and Dome. All paid to institution and outside the submitted work., Mylène Jansen: None declared, Pim de Jong Consultant of: Vifor Pharma and Philips Healthcare, Marloes W. Heijstek: None declared, Julia Spierings: None declared.