Synovial Cellular and Molecular Signatures Stratify Clinical Response to csDMARD Therapy and Predict Radiographic Progression in Early Rheumatoid Arthritis Patients

Copyright © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.
Annals of the Rheumatic Diseases. 2019 Jun;78(6) doi: 10.1136/annrheumdis-2018-214539. Epub 2019 Mar 16.

Abstract

OBJECTIVES:
To unravel the hierarchy of cellular/molecular pathways in the disease tissue of early, treatment-naïve rheumatoid arthritis (RA) patients and determine their relationship with clinical phenotypes and treatment response/outcomes longitudinally.
METHODS:
144 consecutive treatment-naïve early RA patients (<12 months symptoms duration) underwent ultrasound-guided synovial biopsy before and 6 months after disease-modifying antirheumatic drug (DMARD) initiation. Synovial biopsies were analysed for cellular (immunohistology) and molecular (NanoString) characteristics and results compared with clinical and imaging outcomes. Differential gene expression analysis and logistic regression were applied to define variables correlating with treatment response and predicting radiographic progression.
RESULTS:
Cellular and molecular analyses of synovial tissue demonstrated for the first time in early RA the presence of three pathology groups: (1) lympho-myeloid dominated by the presence of B cells in addition to myeloid cells; (2) d iffuse-myeloid with myeloid lineage predominance but poor in B cells nd (3) pauci-immune characterised by scanty immune cells and prevalent stromal cells. Longitudinal correlation of molecular signatures demonstrated that elevation of myeloid- and lymphoid-associated gene expression strongly correlated with disease activity, acute phase reactants and DMARD response at 6 months. Furthermore, elevation of synovial lymphoid-associated genes correlated with autoantibody positivity and elevation of osteoclast-targeting genes predicting radiographic joint damage progression at 12 months. Patients with predominant pauci-immune pathology showed less severe disease activity and radiographic progression.
CONCLUSIONS:
We demonstrate at disease presentation, prior to pathology modulation by therapy, the presence of specific cellular/molecular synovial signatures that delineate disease severity/progression and therapeutic response and may pave the way to more precise definition of RA taxonomy, therapeutic targeting and improved outcomes.

The Role of Dual-Energy Computed Tomography in Musculoskeletal Imaging

Abstract

Dual-energy computed tomography (DECT) enables material decomposition and virtual monochromatic images by acquiring 2 different energy X-ray data sets. DECT can detect musculoskeletal pathologic conditions that CT alone cannot, and that would otherwise require MR imaging. In this review, the authors discuss several useful techniques and applications of DECT in musculoskeletal research: virtual monochromatic images, virtual noncalcium images, gout, iodine map, and tendons.

KEY POINTS
 Dual-energy computed tomography (DECT) can reduce beam hardening artifacts by synthesizing a
virtual monochromatic image and enables detailed evaluation of prosthetic complications.
 DECT can display monosodium urate crystal deposition, which helps to make a correct diagnosis in
atypical gout and precise therapeutic assessment.
 DECT iodine maps can delineate soft tissue inflammation of arthritis and may be beneficial for
evaluating peripheral joints because of its high spatial resolution.

Role of tissue perfusion, muscle strength recovery and pain in rehabilitation after acute muscle strain injury: A randomized controlled trial comparing early and delayed rehabilitation

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Abstract
Muscle strain injuries disrupt the muscle-tendon unit, early rehabilitation is associated with
a faster return to sports (RTS), but the time course of tissue healing remains sparsely
described. The purpose was to examine tissue regeneration and the effectiveness of early
versus delayed rehabilitation onset on functional and structural recovery after strain
injuries. 50 recreational athletes with a severe acute strain injury in their thigh or calf
muscles were randomized to early or delayed rehabilitation onset. Magnetic resonance
imaging (MRI) was obtained initially, 3 and 6 months post injury and dynamic contrastenhanced
MRI (DCE-MRI) estimated tissue inflammation initially and after 6 months. Muscle
strength was determined 5 weeks, 3 and 6 months post injury and a questionnaire
determined soreness, pain and confidence. DCE-MRI microvascular perfusion was higher in
the injured compared to an uninjured muscle acutely (p< 0.01) and after 6 months (p< 0.01),
for both groups (p> 0.05) and unrelated to RTS (p> 0.05). Total volume of the injured muscle
decreased from the acute to the 3 months scan, and to the 6 months scan (p< 0.01) in both
groups. Muscle strength was similar in both groups at any time. There was a non-significant
trend (p≤ 0.1) towards less pain and higher confidence with early rehabilitation. One reinjury
was recorded. In conclusion, our data showed prolonged tissue repair with the initial
response linked to muscle atrophy but did not explain why early rehabilitation onset
accelerated recovery considering that structural and functional recovery was similar with
early and delayed rehabilitation.