A5023769450- Total Knee Arthroplasty Outcomes
- Orthopaedic implants and arthroplasty
- Orthopedic Infections and Treatments
- Osteoarthritis Treatment and Mechanisms
- Hip disorders and treatments
- Hip and Femur Fractures
- Knee injuries and reconstruction techniques
- Cancer-related molecular mechanisms research
- Inflammatory mediators and NSAID effects
- Adipokines, Inflammation, and Metabolic Diseases
- Cell Adhesion Molecules Research
- Physical Activity and Health
- Bone Metabolism and Diseases
- Cytokine Signaling Pathways and Interactions
- Bone and Joint Diseases
- Cardiovascular and exercise physiology
- Bone health and treatments
- Musculoskeletal synovial abnormalities and treatments
- RNA modifications and cancer
- Bone fractures and treatments
- Dental Implant Techniques and Outcomes
- GDF15 and Related Biomarkers
- Cellular Mechanics and Interactions
- Cardiac, Anesthesia and Surgical Outcomes
- Advanced X-ray and CT Imaging
Royal Orthopaedic Hospital
2016-2025
University of Birmingham
2002-2025
Smith Clinic
2023
Hudson Institute
2020
Russells Hall Hospital
2010-2019
NIHR Surgical Reconstruction and Microbiology Research Centre
2019
Dudley Group NHS Foundation Trust
2014
St. Michael's Hospital
2007-2008
University of Toronto
2007
United States Department of Veterans Affairs
1962
Increasing evidence suggests that inflammation plays a central role in driving joint pathology certain patients with osteoarthritis (OA). Since many OA are obese and increased adiposity is associated chronic inflammation, we investigated whether hip exhibited differential pro-inflammatory cytokine signalling peripheral local lymphocyte populations, compared to normal weight patients. No differences either blood or populations were found between normal-weight However, synovial fibroblasts...
Objective To identify long noncoding RNAs (lncRNAs), including intergenic (lincRNAs), antisense RNAs, and pseudogenes, associated with the inflammatory response in human primary osteoarthritis (OA) chondrocytes to explore their expression function OA. Methods OA cartilage was obtained from patients hip or knee following joint replacement surgery. Non‐OA postmortem donors fracture of neck femur. Primary were isolated by collagenase digestion. LncRNA analysis performed RNA sequencing (RNAseq)...
Synovial inflammation is associated with pain severity in patients knee osteoarthritis (OA). The aim here was to determine a population OA, whether synovial tissue from areas exhibited different fibroblast subsets, compared sites not pain. A further compare differences between early and end-stage disease subsets.Patients OA (n = 29) 22) were recruited. Patient reported recorded by questionnaire using an anatomical map. Proton density fat suppressed MRI axial sagittal sequences analysed...
Abstract Background Osteoarthritis (OA), a multifaceted condition, poses significant challenge for the successful clinical development of therapeutics due to heterogeneity. However, classifying molecular endotypes OA pathogenesis could provide invaluable phenotype‐directed routes stratifying subgroups patients targeted therapeutics, leading greater chances success in trials. This study establishes soft joint tissue driven by obesity both load‐bearing and non‐load bearing joints. Methods...
The existing suite of therapies for bone diseases largely act to prevent further loss but fail stimulate healthy formation and repair. We describe an endogenous osteopeptide (PEPITEM) with anabolic osteogenic activity, regulating remodeling in health disease. PEPITEM acts directly on osteoblasts through NCAM-1 signaling promote their maturation new bone, leading enhanced trabecular growth strength. Simultaneously, stimulates inhibitory paracrine loop: promoting osteoblast release the decoy...
To identify long noncoding RNAs (lncRNAs) associated with the inflammatory phenotype of synovial fibroblasts from obese patients osteoarthritis (OA), and to explore expression function these lncRNAs.Synovium was collected normal-weight hip fracture (non-OA; n = 6) (n 8) OA. Expression RNA determined by RNA-sequencing quantitative reverse transcription-polymerase chain reaction. Knockdown lncRNA performed using LNA-based GapmeRs. Synovial fibroblast cytokine production measured enzyme-linked...
Abstract Adiposity and adipokines are implicated in the loss of skeletal muscle mass with age several chronic disease states. The aim this study was to determine effects human obese lean subcutaneous adipose tissue secretome on myogenesis metabolism cells derived from both young (18–30 yr) elderly (>65 individuals. Obese impaired old myoblasts but not myoblasts. Resistin prolifically secreted by myotube thickness nuclear fusion activation classical NFκB pathway. Depletion resistin...
Changes in cellular metabolism have been implicated mediating the activated fibroblast phenotype a number of chronic inflammatory disorders, including pulmonary fibrosis, renal disease and rheumatoid arthritis. The aim this study was therefore to characterise metabolic profile synovial joint fluid fibroblasts under both basal conditions cohort obese normal-weight hip OA patients. Furthermore, we sought ascertain whether modulation pathway could alter their activity. Synovium obtained from...
Synovial inflammation is recognised as a pathological driver of osteoarthritis (OA), degenerative joint disease involving cartilage degradation and pain. Since extracellular vesicles (EVs) have emerged key mediators cellular cross-talk, this study characterised synovial fluid EVs (SFEVs) in OA patients with varying severity, determined their functional effects on articular chondrocytes. were collected from undergoing knee surgery. SFEVs isolated via ultracentrifugation by nanoparticle...
The aim of this project was to analyse the effect contemporary THR bearings on THA survival. This is an updated report our previous analysis with longer follow up and now includes antioxidant-stabilised polyethylene bearings. We combined NJR dataset manufacturing properties sub-divide into conventional (PE) highly crosslinked (XLPE). Only THAs a cementless acetabular component were included. Hospital Episode Statistics (HES) used link ipsilateral surgical procedures for treatment...
ObjectiveTo identify whether patients in lower socioeconomic groups had worse pain and functional levels prior to total knee arthroplasty then establish these poorer post-operative outcomes following arthroplasty.
A total of 20 pairs fresh-frozen cadaver femurs were assigned to four alignment groups consisting relative varus (10 degrees and degrees) valgus degrees), 75 composite two neck geometries also used. In both the femurs, placing component in resulted a significant increase load failure. Placing 10 had no appreciable effect on increasing failure except with native femoral necks. Specimens significantly weaker than neutrally-aligned specimens. The results suggest that retention intact proximal...
The purpose of this study was to determine the effect adiposity on architecture and composition hip OA subchondral bone, examine pathological role adipokines. Femoral heads were collected from normal-weight or over-weight/obese patients with OA. Structural parameters bone determined by MicroCT type I collagen α1/α2 ratio SDS PAGE qRT-PCR in ex-vivo explants. serum concentration adipokines Luminex. resistin primary osteoblasts analysis Wnt pathway signal transduction, nodule formation,...
Adipokines have emerged as central mediators of insulin sensitivity and metabolism, in part due to the known association obesity with metabolic syndrome disorders such type 2 diabetes. Recent studies rodents identified novel adipokine vaspin playing a protective role inflammatory diseases by functioning promoter during stress. However, at present skeletal muscle adipose tissue expression humans is poorly characterised. Furthermore, functional has not been studied. Since major for...
Osteoblast-derived extracellular vesicles (EV) are a collection of secreted (sEVs) and matrix-bound nanoparticles that function as foci for mineral nucleation accumulation. Due to the fact sEVs can be isolated directly from culture medium mineralising osteoblasts, there is growing interest their application regenerative medicine. However, at present therapeutic advancements hindered by lack understanding precise temporal contribution matrix mineralisation. This study advances current...
A disintegrin and metalloprotease 10 (ADAM10) is a transmembrane protein essential for embryonic development, its dysregulation underlies disorders such as cancer, Alzheimer's disease, inflammation. ADAM10 "molecular scissor" that proteolytically cleaves the extracellular region from >100 substrates, including Notch, amyloid precursor protein, cadherins, growth factors, chemokines. has been recently proposed to function six distinct scissors with different depending on association one of...
Robotic-assisted knee replacement systems have been introduced to healthcare services worldwide in an effort improve clinical outcomes for people, although high-quality evidence that they are clinically, or cost-effective remains sparse. Robotic-arm may surgical accuracy and could contribute reduced pain, improved function lower overall cost of total (TKR) surgery. However, TKR with conventional instruments be just as effective quicker cheaper. There is a need robust evaluation this...
Hip resurfacing is an alternative to total hip arthroplasty in which the femoral head surface replaced with a metallic shell, thus preserving most of proximal bone stock. Accidental notching neck during procedure may predispose it fracture. We examined effect on strength femur. Six composite femurs were prepared without superior notch, six inferiorly translated position create 2 mm and 5 notch. intact synthetic also tested. The samples loaded failure axially. A finite element model femur...
Purpose. To assess the lower-limb alignment and posterior tibial slope in Pakistanis. Methods. 40 male 19 female healthy Pakistanis aged 20 to 45 years were recruited. A full weight-bearing anteroposterior radiograph of entire lower limb each subject was obtained. The axial measured based on centres femoral head, knee, ankle. tibiofemoral (TF) angle, knee joint line obliquity angle (angle J), determined. Results. mean TF more varus men than women (178.4° vs. 180.0°, p<0.001). J medially...
Leg length inequality following total hip replacement remains common. In an effort to reduce this occurrence, surgeons undertake pre-operative measurements, templating and use various forms of intraoperative including computer navigation. This study aims delineate which measurement technique is most appropriate for measuring leg from a pelvic radiograph. Three observers took 9600 measurements 100 radiographs. Four lines were constructed on each the radiographs, bisecting acetabular...