Assessment of bone marrow oedema-like lesions using MRI in patellofemoral knee osteoarthritis: comparison of different MRI pulse sequences.

Objective: To compare bone marrow oedema-like lesion (BML) volume in subjects with symptomatic patellofemoral (PF) knee osteoarthritis (OA) using four different MRI sequences and to determine reliability of BML volume assessment using these sequences and their correlation with pain.

Methods: 76 males and females (mean age 55.8 years) with symptomatic patellofemoral knee OA had 1.

Evaluating the cost and clinical effectiveness of long-acting, injectable aripiprazole and paliperidone palmitate once a month in a real-world setting.

Background: Antipsychotics are an effective treatment option for patients with schizophrenia and several long-acting injectables (LAIs), including risperidone, olanzapine, paliperidone, and aripiprazole are available in the UK. Treatment adherence is an issue in severe mental illness and LAIs have been hypothesized to offer clinical advantages over their oral equivalents. However, meta-analyses of randomized clinical trials and mirror-image studies have yielded equivocal results and have focused on economic rather than clinical outcomes.

Recommendations for acquisition and interpretation of MRI of the spine and sacroiliac joints in the diagnosis of axial spondyloarthritis in the UK.

Objectives: To develop evidence-based recommendations on the use of MRI in the diagnosis of axial SpA (axSpA).

Methods: A working group comprising nine rheumatologists and nine musculoskeletal radiologists with an interest in axSpA was established, with support from the British Society of Spondyloarthritis (BRITSpA). Two meetings were held.

Imaging calcinosis in patients with systemic sclerosis by radiography, computerised tomography and magnetic resonance imaging.

Introduction: Objective outcome measures are needed to facilitate clinical trials of much needed treatments for calcinosis in systemic sclerosis (SSc). Our primary aim was to compare radiography, computed tomography (CT) and magnetic resonance imaging (MRI) to measure calcinotic lesions. Secondary objectives included to examine reproducibility of radiography and MRI, and inter-rater reliability of MRI.

Measurement of synovial tissue volume in knee osteoarthritis using a semiautomated MRI-based quantitative approach.

Purpose: Synovitis is common in knee osteoarthritis and is associated with both knee pain and progression of disease. Semiautomated methods have been developed for quantitative assessment of structure in knee osteoarthritis. Our aims were to apply a novel semiautomated assessment method using 3D active appearance modeling for the quantification of synovial tissue volume (STV) and to compare its performance with conventional manual segmentation.

Effect of Vitamin D supplementation on synovial tissue volume and subchondral bone marrow lesion volume in symptomatic knee osteoarthritis.

Background: Data from a recent clinical trial of vitamin D therapy in knee OA suggests that, compared to placebo, vitamin D therapy may be associated with a reduction in effusion-synovitis. Our aim was, using contrast-enhanced (CE) magnetic resonance imaging (MRI), to examine the effect of vitamin D therapy on synovial tissue volume (STV) and also subchondral bone marrow lesion (BML) volume in men and women with symptomatic knee OA.

Methods: Data was acquired from participants who took part in a randomised placebo-controlled trial (UK VIDEO) investigating the effect of vitamin D therapy (800 IU cholecalciferol daily) on radiographic joint space narrowing.

[18F]Florbetapir positron emission tomography: identification of muscle amyloid in inclusion body myositis and differentiation from polymyositis.

Objectives: With the tools available currently, confirming the diagnosis of inclusion body myositis (IBM) can be difficult. Many patients are initially misdiagnosed with polymyositis (PM). In this observational study at a UK adult neuromuscular centre, we investigated whether amyloid positron emission tomography could differentiate between IBM and PM.

The Efficacy of a Lateral Wedge Insole for Painful Medial Knee Osteoarthritis After Prescreening: A Randomized Clinical Trial.

Objective: Lateral wedge shoe insoles decrease medial knee loading, but trials have shown no effect on pain in medial knee osteoarthritis (OA). However, loading effects of insoles are inconsistent, and they can increase patellofemoral loading. We undertook this study to investigate the hypothesis that insoles would reduce pain in preselected patients.

Developing a toolkit for the assessment and monitoring of musculoskeletal ageing.

The complexities and heterogeneity of the ageing process have slowed the development of consensus on appropriate biomarkers of healthy ageing. The Medical Research Council-Arthritis Research UK Centre for Integrated research into Musculoskeletal Ageing (CIMA) is a collaboration between researchers and clinicians at the Universities of Liverpool, Sheffield and Newcastle. One of CIMA's objectives is to 'Identify and share optimal techniques and approaches to monitor age-related changes in all musculoskeletal tissues, and to provide an integrated assessment of musculoskeletal function'-in other words to develop a toolkit for assessing musculoskeletal ageing.

An assessment of F-FDG PET/CT for thoracic screening and risk stratification of pulmonary nodules in multiple endocrine neoplasia type 1.

Context: Bronchopulmonary neuroendocrine tumours (bpNETs) and thymic carcinoid (ThC) are features of multiple endocrine neoplasia type 1 (MEN 1), and surveillance guidelines recommend periodic thoracic imaging. The optimal thoracic imaging modality and screening frequency remain uncertain as does the prognosis of small lung nodules when identified.

Objectives: To evaluate fluorodeoxyglucose positron emission tomography/computed tomography ( F-FDG PET/CT) for identification and prognostic assessment of thoracic lesions in MEN 1.

With a biomechanical treatment in knee osteoarthritis, less knee pain did not correlate with synovitis reduction.

Background: Braces are used to treat pain in patellofemoral joint osteoarthritis (PFJOA). In a trial, we previously reported pain improvement after 6-weeks brace use. The pain reduction did not correlate with changes in Magnetic Resonance Imaging (MRI) assessed Bone Marrow Lesion volume or static synovial volume.

Plantar plate pathology is associated with erosive disease in the painful forefoot of patients with rheumatoid arthritis.

Background: Disease-related foot pathology is recognised to have a significant impact on mobility and functional capacity in the majority of patients with rheumatoid arthritis (RA). The forefoot is widely affected and the metatarsophalangeal (MTP) joints are the most common site of symptoms. The plantar plates are the fibrocartilaginous distal attachments of the plantar fascia inserting into the five proximal phalanges.

Structural predictors of response to intra-articular steroid injection in symptomatic knee osteoarthritis.

Background: The aim was to examine if structural factors could affect response to intra-articular steroid injections (IASI) in knee osteoarthritis (OA).

Method: Persons with painful knee OA participated in an open-label trial of IASI where radiographic joint space narrowing (JSN) and Kellgren-Lawrence (KL) grade, whole-organ magnetic resonance imaging (MRI) scores (WORMS) and quantitative assessment of synovial tissue volume (STV) were assessed on baseline images. Participants completed the Knee Injury and Osteoarthritis Outcome Score (KOOS) and a question about knee pain with a visual analogue scale for pain during nominated activity (VAS), and Outcome Measures in Rheumatology (OMERACT)-Osteoarthritis Research Society International (OARSI) criteria were used to assess responder status within 2 weeks (short term) and 6 months (longer term).

Functional characterization of CFI-402257, a potent and selective Mps1/TTK kinase inhibitor, for the treatment of cancer.

Loss of cell-cycle control is a hallmark of human cancer. Cell-cycle checkpoints are essential for maintaining genome integrity and balanced growth and division. They are specifically deregulated in cancer cells and contain regulators that represent potential therapeutic targets.

BMI independently relates to glycaemia in patients with severe enduring mental illness (SMI).

Background: People with severe mental illness (SMI) have higher rates of diabetes than the general population.

Aims: To assess the type-2 diabetes screening rates in primary care and the relation between body mass index (BMI) and dysglycaemia for patients on the SMI register in the Cheshire region of the United Kingdom.

Methods: The setting was 24 general practices in Central and Eastern Cheshire, United Kingdom.

Design and optimization of (3-aryl-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-ones as potent PLK4 inhibitors with oral antitumor efficacy.

Previous efforts from our laboratory demonstrated that (E)-3-((3-(E)-vinylaryl)-1H-indazol-6-yl)methylene)-indolin-2-ones are potent PLK4 inhibitors with in vivo anticancer efficacy upon IP dosing. As part of a continued effort to develop selective and orally efficacious inhibitors, we examined variations on this theme wherein 'directly-linked' aromatics, pendant from the indazole core, replace the arylvinyl moiety. Herein, we describe the design and optimization of this series which was ultimately superseded by (3-aryl-1H-indazol-6-yl)spiro[cyclopropane-1,3'-indolin]-2'-ones.

Discovery of Pyrazolo[1,5-a]pyrimidine TTK Inhibitors: CFI-402257 is a Potent, Selective, Bioavailable Anticancer Agent.

This work describes a scaffold hopping exercise that begins with known imidazo[1,2-a]pyrazines, briefly explores pyrazolo[1,5-a][1,3,5]triazines, and ultimately yields pyrazolo[1,5-a]pyrimidines as a novel class of potent TTK inhibitors. An X-ray structure of a representative compound is consistent with 1(1)/2 type inhibition and provides structural insight to aid subsequent optimization of in vitro activity and physicochemical and pharmacokinetic properties. Incorporation of polar moieties in the hydrophobic and solvent accessible regions modulates physicochemical properties while maintaining potency.

Discovery of 4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamides as novel, highly potent and selective, orally bioavailable inhibitors of Tyrosine Threonine Kinase, TTK.

TTK/Mps1 is a key kinase controlling progression of cell division via participation in the mitotic spindle assembly checkpoint and is overexpressed in a number of human cancers. Herein we report the discovery of 4-(4-aminopyrazolo[1,5-a][1,3,5]triazin-8-yl)benzamides as a potent, novel class of TTK inhibitors. The series was identified by means of bioisosteric replacement of the related imidazopyrazine and imidazopyridazine scaffolds.

A prospective, single-centre, randomised study evaluating the clinical, imaging and immunological depth of remission achieved by very early versus delayed Etanercept in patients with Rheumatoid Arthritis (VEDERA).

Background: Rheumatoid arthritis (RA) is a chronic inflammatory arthritis, with significant impact on quality of life and functional status. Whilst biologic disease modifying anti-rheumatic drugs (bDMARD) such as tumour necrosis factor-inhibitor (TNFi) agents have revolutionised outcomes in RA, early diagnosis with immediate conventional therapy, titrated in a treat to target approach is also associated with high remission rates. The main aim of the VEDERA study (Very Early versus Delayed Etanercept in Rheumatoid Arthritis) is to assess the depth of remission, sustainability of remission and immunological normalisation induced by very early TNFi with etanercept (ETN) or standard of care +/- delayed ETN.

MRI appearances of the femur following bone graft harvesting using the Reamer-Irrigator-Aspirator.

The reamer-irrigator-aspirator is increasingly being used to harvest autologous bone graft from the femur. The purpose of this study was to investigate the extent of neo-vascularisation and new bone formation that occurs within the medulla following the procedure, and determine if new bone formation would potentially allow a repeat bone harvest in those individuals subsequently requiring further bone graft. Eleven patients who had undergone femoral bone harvest were examined with MRI.

Whole-body MRI of patients with polymyalgia rheumatica identifies a distinct subset with complete patient-reported response to glucocorticoids.

Objectives: To determine whether whole-body MRI defines clinically relevant subgroups within polymyalgia rheumatica (PMR) including glucocorticoid responsiveness.

Methods: 22 patients with PMR and 16 with rheumatoid arthritis (RA), untreated and diagnosed by consultant rheumatologists, underwent whole-body, multiple-joint MRI, scored by two experts. Patients with PMR reported whether they felt 'back to normal' on glucocorticoid therapy and were followed for a median of 2 years.

Synovial tissue volume: a treatment target in knee osteoarthritis (OA).

Background: Synovitis occurring frequently in osteoarthritis (OA) may be a targeted outcome. There are no data examining whether synovitis changes following intra-articular intervention.

Methods: Persons aged 40 years and older with painful knee OA participated in an open label trial of intra-articular steroid therapy.