Karina Wright

A strong body of evidence is established that links sex-hormone-regulated physiological processes across the female life course with increased risk of osteoarthritis (OA), although the strength and nature of these associations vary by joint site and OA phenotype. Much of the available mechanistic evidence relates to knee OA with comparatively less evidence available for hip and hand OA. These include reproductive milestones (menarche and menopause), major life events such as childbirth (parity), and sex-hormone-regulated physiological functions, including menstruation and breastfeeding. Many of these have also been shown to associate with poorer surgical and non-surgical responses to musculoskeletal (MSK) treatment. A thorough multidisciplinary analysis of sex-associated differences in MSK outcomes and OA risk across the female life course is long overdue. This thematic narrative review has been conducted by a multidisciplinary team comprising experts in fundamental biology, mechanobiology, immunology, orthopaedic surgery, pain medicine and gynaecology. The review will examine in detail early life and puberty (menarche), reproductive years (menstrual cycling and injury risk, contraception, parity and breastfeeding), midlife transition (perimenopause, menopause, and treatments) and clinical interactions (response to surgical and non-surgical interventions). Biological considerations in each life-course phase/transition will focus on the hormonal milieu, biomechanical influences, immune and metabolic functions and pain pathways.

Objective: Evaluate the association of sex and age at surgery with time to total knee arthroplasty (TKA) following knee cartilage surgery in UK Biobank (UKB) participants. Design: Participants with a history of knee cartilage surgery were classified into four surgical subgroups: cartilage repair, debridement, microfracture, and unicompartmental knee arthroplasty. Time from index surgery to primary TKA in each group was analysed using the Kaplan-Meier method and the sexes compared using log-rank tests. Cox proportional hazards regression evaluated associations between age at surgery, sex, and surgery type with risk of progression to TKA. Results: The study included 1,967 males and 1,741 females. Log‑rank testing demonstrated significant sex‑based differences in time to TKA following debridement ( P = 0.002) and microfracture ( P = 0.003), with shorter TKA‑free survival observed in females. Cox regression showed that female sex was associated with a higher hazard of progression to TKA compared with male sex (hazard ratio [HR] = 1.19, P = 0.021). Increasing age at surgery was associated with increased risk (HR = 1.05 per year, P < 0.0001). Conclusion: Female sex and older age at surgery were associated with a higher risk of progression to TKA following cartilage surgery. Sex‑specific differences in time to TKA were most evident after debridement and microfracture. These findings describe associations observed within the constraints of available UKB data.

Background: Emerging evidence indicates that the liver plays a key role in spinal cord injury (SCI) pathophysiology. Method: This study reanalysed published proteomic datasets from rat models and patients with SCI using bioinformatics and literature/database searches. The aim was to identify liver-specific molecular signatures in SCI blood samples and to link these to severity and neurological recovery at various time points (acute/sub-acute and chronic). Results: Across species, a high proportion of injury severity and neurological recovery-associated proteins were linked to liver function. Notably, non-improvers exhibited prolonged sub-acute proinflammatory responses. These changes were not restricted to classical acute-phase reactants but reflected coordinated alterations in hepatic metabolic and synthetic pathways. Pathway analysis consistently highlighted Liver X Receptor /Retinoic X Receptor (LXR/RXR), complement system/cascade and DHCR24 signalling pathways, with predicted directional changes linked to recovery status. Several proteins were identified and categorised as markers of liver dysfunction, metabolic function, complement/coagulation factors and/or acute-phase proteins. Alpha-2-HS-glycoprotein (AHSG) and afamin (AFM) were commonly dysregulated across species datasets, suggesting conserved roles in inflammation and lipid metabolism. Further associations with liver pathologies such as fibrosis and cirrhosis, particularly in non-improvers, were identified. Conclusion This work builds on emerging evidence of hepatic involvement in SCI by providing cross-species, time-resolved proteomic support for altered liver-associated protein output following injury. Together, these findings underscore the central role of hepatic responses in SCI, highlighting liver-associated proteins and pathways as candidate biomarkers that may aid in stratifying recovery trajectories and informing clinical prognostication.

Aims: This study examines the ability of YOLO (You Only Look Once) 11x, a widely used and state of the art object detection model, trained on publicly available datasets, to identify and count neutrophils in tissue samples taken at prosthetic joint revision surgery, with the objective of automating a laborious but necessary part of the diagnostic workup for periprosthetic joint infection. Methods: Three datasets containing blood film microscopic slides with neutrophils were downloaded, combined, and labelled. The resulting dataset of 3,923 images was augmented with ten additional histological slides from periprosthetic tissue, taken at the time of revision surgery (5 infected, 5 sterile), and split into training (70%), validation (20%), and test (10%) sets. The dataset was used to train YOLO 11x object detection model optimized for a mean average precision above 50%. The trained network was tested on a ground truth specimen and histological whole slide images from 19 additional cases, previously unseen by the model, for validation. The threshold for diagnosis of infection on histological sections was set at more than five neutrophils per 0.2 mm ² (equivalent to one high-powered microscope field). Results: The model performed well as ground truth image returned precision at 82%, recall (sensitivity) 79%, and F1 harmonic mean 80%. When assessed against formal histopathological, microbiological, and multidisciplinary team (MDT) diagnosis, precision was 78%, 80%, and 90%; recall 78%, 89%, and 82%; and F1 score 78%, 84%, and 86%, respectively. Against the definitive MDT diagnosis, our model identified nine out of the ten infected cases and excluded seven out of nine cases that were not infected. Conclusion: This study demonstrates ability of the trained model to identify neutrophils in tissue taken at revision surgery and could assist in diagnosis of periprosthetic infection. Further work is needed to improve confidence in the identifications and diagnostic accuracy of periprosthetic infection. Cite this article: Bone Joint Res 2026;15(3):238–247.

Metabolic profiling enables comprehensive characterisation of the small molecules that are part of the biochemical composition of biological fluids. The most widely profiled biofluids include serum and plasma. Additionally synovial fluid provides a direct reflection of the metabolomic environment of joints and holds promise for biomarker discovery in arthropathies. However, the reproducibility of metabolomics data is highly sensitive to pre-analytical variation, and at the present time, standardised protocols for synovial fluid remain underdeveloped. This review aims to identify and evaluate the existing literature on effects of biofluid pre-analytical handling treatments on metabolic profiles. This review was conducted and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. A search was carried out to identify studies employing LC-MS, GC-MS, and NMR spectroscopy for the investigation of factors including sample collection variables, pre-centrifugation conditions, centrifugation parameters, post-centrifugations conditions, sample storage conditions, and freeze/thaw cycling. Best practice recommendations emerging from this review include the use of additive free serum and heparin plasma tubes, the centrifugation of samples within two hours of collection, immediate storage of samples at −80 °C, and avoidance of repeated freeze/thaw cycling. However, while pre-analytical influences have been extensively characterised for plasma and serum, evidence for synovial fluid remains limited. Overall, the findings highlight the existing recommendations for plasma and serum and demonstrate the need for standardised pre-analytical protocols and validation of quality control markers to advance synovial fluid metabolomics.

Although research in cell-based therapy is expanding, little is known about patient experience in cell therapy trials to-date. This study explores the experience and attitudes of participants involved in the ASCOT randomized controlled trial, a long-term orthopedic study comparing different cell therapies for the treatment of knee articular cartilage defects. The clinical and rehabilitation experience of participants, and their attitudes relating to i) patient and public involvement (PPIE) in research and ii) future research on cellular therapy and clinical trials were explored through questionnaires. To gather this information, the utility of an end-of-trial event to reengage participants was evaluated. Despite the anticipated high burden, overall trial experience was reported as highly positive. Communication and ongoing engagement between patients and both the clinical and research teams may have contributed to this. Key challenges identified for future research include the need for early and transparent communication regarding trial results, and greater support to facilitate active PPIE involvement. The end-of-trial engagement event demonstrated feasibility and value as a model to gather this important PPIE data for future studies. This study highlights the importance of integrating participant perspectives to optimize trial design and delivery in future cell therapy research.

Allogeneic chondrocyte therapies present an attractive alternative to existing autologous therapies for the repair of cartilage defects, enabling the selection of optimal donor cells and streamlined manufacturing processes. This study investigates the potential of juvenile chondrocytes derived from human infantile (aged 0–4 y) polydactyly digits and the iliac apophysis for cartilage repair using Good Manufacturing Practice bioreactor expansion. Iliac apophysis (n = 4) and polydactyly tissues (n = 4) were assessed histologically. Chondrocytes were isolated enzymatically and cultured using standard tissue culture plastic (TCP) methodology. Upon sufficient cell expansion, chondrocytes were seeded into the Quantum^® bioreactor system or onto TCP (±vitronectin coating). The manufactured chondrocytes growth rates, total cell yields, chondrogenic pellet forming capacity (GAG/DNA, histology), immunoprofiles (flow cytometry) and gene expression (RT-qPCR) were assessed. Equivalent chondrocyte numbers were isolated from polydactyly and iliac apophysis donors per wet weight of tissue. Quantum^®-expanded chondrocytes from both sources yielded comparable cell numbers; however, growth was slowed in the Quantum^® compared to TCP. Polydactyly and iliac apophysis-derived chondrocytes expressed chondrocyte cell surface markers (CD166, CD44, CD151, SOX9) and formed chondrogenic pellets. Quantum^® bioreactor expansion did not alter, gene expression or capacity to form glycosaminoglycans (GAGs (normalised to DNA content)) compared to matched TCP expansion. Juvenile cartilage donors are a promising chondrocyte source for the development of an allogeneic therapy. This novel study expanding juvenile chondrocytes in the Quantum^® GMP-compliant bioreactor suggests that culture conditions may need modification to improve growth, whilst retaining cartilage forming capacity.

Objective: To determine the association between socioeconomic deprivation and short-term patient-reported clinical outcomes following autologous chondrocyte implantation (ACI). Design: All patients receiving knee ACI between 1996 and 2020 in our center were identified. Socioeconomic deprivation of their residential area was quantified using the Index of Multiple Deprivation (IMD). Patient-reported 1-year Lysholm and Intermittent and Constant Osteoarthritis Pain (ICOAP) scores were used as outcome measures in the analyses. After transformation to ensure normal distributions (where required), linear multivariable regression was used to analyze the relationship between IMD and 1-year Lysholm score, adjusting for demographic characteristics (age, sex, body mass index [BMI], and smoking) and baseline Lysholm. Results: Three hundred and ninety-one patients with a mean age of 50 years (range = 16-84; 266 male) were identified. Median BMI was 27 (17-47), with 138 patients overweight and 105 obese. Seventy-seven patients lived in upper and 41 in lower quintile deprivation areas. The mean baseline Lysholm score was 49.8 ± 17.3 SD, improving to 66.5 ± 21.3 SD at 1 year. Mean 1-year Lysholm scores were significantly lower with increasing area deprivation scores, adjusted for demographic factors. Specifically, areas with high unemployment levels, being female, or having a lower baseline Lysholm were associated with poorer outcomes, but age, BMI, smoking, or higher income deprivation were not. Conclusion: This study demonstrates poorer functional outcomes following ACI in patients from more deprived areas, indicating future studies should consider neighborhood deprivation as a confounding factor. Furthermore, targeting patients from areas with higher deprivation with additional interventions/community support may improve their outcomes.

Background/Objectives: The diagnosis of prosthetic joint infection remains difficult. Microbiological cultures frequently have false-positive and false-negative results. This study investigates whether rapid nanopore sequencing can be used to aid the identification of bacteria causing prosthetic joint infection for more timely identification and treatment. Methods: Nineteen patients who had revision surgery following total joint arthroplasty were included in this study. Of these, 15 patients had an infected joint arthroplasty. All patients had joint fluid aspirated at the time of revision surgery. The DNA was extracted from these fluid aspirates, and rapid nanopore sequencing was performed using the MinION device from Oxford Nanopore Technologies. The sequencing data was trimmed to improve quality and filtered to remove human reads using bioinformatic tools. Genomic sequence classification was performed using the Basic Local Alignment Search Tool. The results were filtered by read length and sequence identity score. The European Bone and Joint Infection Society criteria were used as a standard to identify infected and not infected patients. Confusion tables were used to calculate accuracy and F1 score based on this criteria and the nanopore sequencing results. Results: Microbiological cultures and nanopore sequencing had an accuracy of 68% and 74%, respectively. However, combining both results predicted infection accurately in 94% of cases (F1 score 96%). Conclusions: Nanopore sequencing has the potential to aid identification of bacteria causing prosthetic joint infection and may be useful as a supplementary diagnostic tool.