In relation to regenerative therapies in osteoarthritis and cartilage repair, mesenchymal stromal cells (MSCs) have immunomodulatory functions and influence macrophage behaviour. Macrophages exist as a spectrum of pro-(M1) and anti-(M2) inflammatory phenotypic subsets. In the context of cartilage repair, we investigated MSC-macrophage crosstalk, including specifically the priming of cartilage cells by macrophages to achieve a regenerative rather than fibrotic outcome. Human monocytes were isolated from blood cones and differentiated towards M1 and M2 macrophages. Monocytes (Mo), M1 and M2 macrophages were cultured directly and indirectly (trans-well system) with human bone marrow derived MSCs. MSCs were added during M1 polarisation and separately to already induced M1 cells. Outcomes (M1/M2 markers and ligands/receptors) were evaluated using RT-qPCR and flow cytometry. Influence on chondrogenesis was assessed by applying M1 and M2 macrophage conditioned media (CM) sequentially to cartilage derived cells (recapitulating an acute injury environment). RT-qPCR was used to evaluate chondrogenic/fibrogenic gene transcription. The ratio of M2 markers (CD206 or CD163) to M1 markers (CD38) increased when MSCs were added to Mo/M1 macrophages, regardless of culture system used (direct or indirect). Pro-inflammatory markers (including TNFβ) decreased. CXCR2 expression by both M1 macrophages and MSCs decreased when MSCs were added to differentiated M1 macrophages in transwell. When adding initially M1 CM (for 12 hours) followed by M2 CM (for 12 hours) sequentially to chondrocytes, there was a significant increase of Aggrecan and Collagen type 2 gene expression and decrease in fibroblastic cell surface markers (PDPN/CD90). Mo/M1 macrophages cultured with MSCs, directly or indirectly, are shifted towards a more M2 phenotype. Indirect culture suggests this effect can occur via soluble signaling mediators. Sequential exposure of M1CM followed by M2CM to chondrocytes resulted in increased chondrogenic and reduced fibrotic gene expression, suggesting that an acute pro-inflammatory stimulus may prime chondrocytes before repair.
This study assessed quality of life (QoL) in patients having external fixation for treatment of osteomyelitis and fracture-related infection (OM/FRI). Patients who had surgery for OM/FRI and who completed the EuroQoL EQ-5D-5L or EQ-5D- 3L questionnaires, were identified between 2010 and 2020. Patients were followed-up for 2 years after surgery. QoL was compared between patients who had either an Ilizarov frame or a monolateral external fixator with those who did not receive external fixation.Aim
Method
To compare outcomes of PJI in relation to treatment method versus classification using the JS-BACH system. Patients having surgery for EBJIS Criteria Confirmed PJI between 2010–2015 were included. Index surgical procedures were 1-stage or 2-stage revision or debridement and implant retention (DAIR). Patients completed the EuroQol EQ-5D-3L questionnaire and were followed clinically to a median of 4.7 years (IQR 2.7–6.7 years). Patients were stratified using the JS-BACH classification1 into either ‘Uncomplicated’, ‘Complex’ or having ‘Limited treatment options’, by two separate classifiers, blinded to clinical outcome.Aim
Method
Calcaneal osteomyelitis remains a difficult condition to treat with high rates of recurrence and below knee amputation; particularly in cases of severe soft tissue destruction. This study assesses the outcomes of combined ortho-plastics treatment of complex calcaneal osteomyelitis. A retrospective review was performed of all patients who underwent combined single stage ortho-plastics treatment of calcaneal osteomyelitis (2008- 2022). Primary outcome measures were osteomyelitis recurrence and BKA. Secondary outcome measures included flap failure, operative time, complications, length of stay.Aim
Method
To investigate the impact of waiting for surgical treatment for bone and joint infection (BJI) on patient self-reported quality of life (QoL). Patients presenting to clinic between January 2019 and February 2020 completed the EuroQol EQ-5D-5L questionnaire. Patients were divided into three groups: surgery performed; on the waiting list for surgery; or decision for non-operative management. All patients were followed-up for 2 years. The EQ-index score was calculated and change from presentation to 1-year and 2-year follow-up was compared across the 3 groups. Mortality at final follow-up was measured in all groups.Aim
Method
Pin site infection (PSI) is a common complication of external fixators. PSI usually presents as a superficial infection which is treated conservatively. This study investigated those rare cases of PSI requiring surgery due to persistent osteomyelitis (OM), after pin removal. In this retrospective cohort study we identified patients who required surgery for an OM after PSI (Checketts-Otterburn Classification Grade 6) between 2011 and 2021. We investigated patient demographics, aetiology of the OM, pathogen and histology, treatment strategies and complications. Infection was confirmed using the 2018 FRI Consensus Definition. Successful outcome was defined as an infection-free interval of at least 24 months following surgery, which was defined as minimum follow-up.Aim
Method
Patient quality of life (QoL) in untreated bone infection was compared to other chronic conditions and stratified by disease severity. Patients referred for treatment of osteomyelitis (including fracture related infection) were identified prospectively between 2019 and 2023. Patients with confirmed infection completed the EuroQol EQ-5D-5L questionnaire. Clinicians blinded to EQ-index score, grouped patients according to JS-BACH Classification into ‘Uncomplicated’, ‘Complex’ or ‘Limited treatment options’. A systematic review of the literature was performed of other conditions that have been stratified using EQ-index score.Aim
Method
In relation to regenerative therapies in osteoarthritis and cartilage repair, mesenchymal stromal cells (MSCs) have immunomodulatory functions and influence macrophage behaviour. Macrophages exist as a spectrum of pro-(M1) and anti-(M2) inflammatory phenotypic subsets. In the context of cartilage repair, we investigated MSC-macrophage crosstalk, including specifically the priming of cartilage cells by macrophages to achieve a regenerative rather than fibrotic outcome. Human monocytes were isolated from blood cones and differentiated towards M1 and M2 macrophages. Monocytes (Mo), M1 and M2 macrophages were cultured directly and indirectly (trans-well system) with human bone marrow derived MSCs. MSCs were added during M1 polarisation and separately to already induced M1 cells. Outcomes (M1/M2 markers and ligands/receptors) were evaluated using RT-qPCR and flow cytometry. Influence on chondrogenesis was assessed by applying M1 and M2 macrophage conditioned media (CM) sequentially to cartilage derived cells (recapitulating an acute injury environment). RT-qPCR was used to evaluate chondrogenic/fibrogenic gene transcription.Abstract
Objectives
Methods
Smoking is known to impair wound healing and to increase the risk of peri-operative adverse events and is associated with orthopaedic infection and fracture non-union. Understanding the magnitude of the causal effect on orthopaedic infection recurrence may improve pre-operative patient counselling. Four prospectively-collected datasets including 1173 participants treated in European centres between 2003 and 2021, followed up to 12 months after surgery for clinically diagnosed orthopaedic infections, were included in logistic regression modelling with Inverse Probability of Treatment Weighting for current smoking status [1–3]. Host factors including age, gender and ASA score were included as potential confounding variables, interacting through surgical treatment as a collider variable in a pre-specified structural causal model informed by clinical experience. The definition of infection recurrence was identical and ascertained separately from baseline factors in three contributing cohorts. A subset of 669 participants with positive histology, microbiology or a sinus at the time of surgery, were analysed separately.Aim
Methods
Local antibiotic treatment for bone and joint infections offers direct delivery of high concentrations of antibiotics with reduced systemic exposure and favourable safety profile. However, the possibility of prolonged release of antibiotics at sub-therapeutic levels creates concern about the possible development of antimicrobial resistance. We investigated patients with recurrent bone and joint infection for evidence of antimicrobial resistance emerging from the use of local antibiotics. 125 patients with recurrent infection (prosthetic joint infection, fracture related infection and osteomyelitis) in the UK between 2007 and 2021 were identified. Electronic patient records (including operative notes, pathology results and prescriptions) were reviewed to extract site of infection, date of surgery, the use of local antibiotics, culture results, empiric and definitive antibiotic therapy. All antibiotic sensitivity results were recorded as sensitive, intermediate or resistant according to contemporary guidelines (BSAC and EUCAST).Aim
Method
Recurrence of bone and joint infection, despite appropriate therapy, is well recognised and stimulates ongoing interest in identifying host factors that predict infection recurrence. Clinical prediction models exist for those treated with DAIR, but to date no models with a low risk of bias predict orthopaedic infection recurrence for people with surgically excised infection and removed metalwork. The aims of this study were to construct and internally validate a risk prediction model for infection recurrence at 12 months, and to identify factors that predict recurrence. Predictive factors must be easy to check in pre-operative assessment and relevant across patient groups. Four prospectively collected datasets including 1173 participants treated in European centres between 2003 and 2021, followed up to 12 months after surgery for orthopaedic infections, were included in logistic regression modelling [1–3]. The definition of infection recurrence was identical and ascertained separately from baseline factors in three contributing cohorts. Eight predictive factors were investigated following Aim
Methods
To assess whether recurrence of PJI and osteomyelitis impacts patient-reported quality of life (QoL). We studied patients receiving surgical treatment for confirmed PJI or osteomyelitis in one of 26 centres in the UK. Patients completed the EQ-5D-3L questionnaire, directly after surgery, at day 14, day 42, day 120 and day 365 after surgery and were assessed for evidence of recurrence.Aim
Method
We reviewed a cohort of individuals with recurrent orthopaedic infection to describe the relative rates of microbial persistence vs re-infection at recurrence surgery. A cohort of 125 individuals with recurrent infection (prosthetic joint infection, fracture-related infection and osteomyelitis) from two centres in the UK between 2007 and 2021. Electronic patient records were reviewed to identify culture results from surgical samples at index surgery and the next operation for recurrent infection. Antibiotic sensitivity results were recorded as sensitive, intermediate or resistant according to contemporary sensitivity testing guidelines.Aim
Method
To compare pre-referral microbiology and previous bone excision in long bone osteomyelitis with intra-operative microbiology from a specialist centre. A prospective observational cohort study of patients referred to a single tertiary centre who met the following criteria: (i) aged ≥18 years, (ii) received surgery for long bone osteomyelitis and (iii) met diagnostic criteria for long bone osteomyelitis. Patient demographics, referral microbiology and previous surgical history were collected at the time of initial clinic appointment. During surgery, a minimum of 5 intra-operative deep tissue samples were sent for microbiology. Antimicrobial options were classified from the results of susceptibility testing using the BACH classification of long bone osteomyelitis as either Ax (unknown or culture negative), A1 (good options available) or A2 (limited options available). The cultures and susceptibility of pre-referral microbiology were compared to the new intra-operative sampling results. In addition, an association between previous osteomyelitis excision and antimicrobial options were investigated.Aim
Method
To investigate self-reported quality of life (QoL) in patients with osteomyelitis referred to a specialist centre in the UK and investigate the relationship between QoL and BACH classification. All patients newly referred to a specialist bone infection clinic at a single tertiary centre within the UK between January 2019 and February 2020 were prospectively included. Diagnosis of osteomyelitis was made according to the presence of clinical and radiological criteria for ≥6 months. An EQ-5D-5L questionnaire and visual analogue score (VAS) were completed during the initial clinic appointment. Long-bone osteomyelitis was classified by the attending orthopaedic surgeon using the BACH classification system as either uncomplicated, complex or with limited options available.1 Patients managed non-operatively were subclassified into those who were (i) unfit to receive an operation or (ii) fit and well with stable disease. EQ-5D index scores were compared to a published UK value set of 41 chronic health conditions within the UK.2Aim
Method
This study assesses the ability of the JS-BACH classification of bone infection to predict clinical and patient-reported outcomes in prosthetic joint infection (PJI). Patients who received surgery for suspected PJI at two specialist bone infection centres within the UK between 2010 and 2015 were classified using the JS-BACH classification into either ‘uncomplicated’, ‘complex’ or ‘limited options’. All patients were classified by two clinicians blinded to outcome, with any discrepancies adjudicated by a third reviewer. At the most recent follow-up, patients were assessed for (i) any episode of recurrence since the index operation and (ii) the status of the joint. A Cox proportional-hazard model assessed significant predictors of recurrence following the index procedure. Patient-reported outcomes included the EuroQol EQ-5D-3L index score and the EQ-visual analogue score (VAS) at 0, 14, 42, 120 and 365 days following the index operation.Aim
Method
This study assesses self-reported quality of life (QoL) in patients with osteomyelitis referred to a specialist centre in the UK. All patients newly referred to a specialist tertiary bone infection clinic within the UK between January 2019 and February 2020 were prospectively included. Diagnosis of osteomyelitis was made according to the presence of clinical and radiological criteria for ≥6 months. An EQ-5D-5L questionnaire and visual analogue score (VAS) were completed during the initial clinic appointment. Long-bone osteomyelitis was classified by the attending orthopaedic surgeon using the BACH classification system as either uncomplicated, complex or with limited options available. Patients managed non-operatively were subclassified into those who were (i) unfit to receive an operation or (ii) fit and well with stable disease. EQ-5D index scores were compared to a published UK value-set of 41 chronic health conditions within the UK.Introduction
Materials and Methods
Patients with long-bone osteomyelitis are frequently referred with limited microbiological information. This study compared pre-referral microbiology in long bone osteomyelitis with intra-operative microbiology from a specialist centre. All patients referred to a single tertiary centre between February 2019 and February 2020, aged ≥18 years and received surgery for confirmed long-bone osteomyelitis were included. Patient demographics, referral microbiology and previous surgical history were collected at the time of initial clinic appointment. During surgery, a minimum of 5 intra-operative deep tissue samples were sent for microbiology. Antimicrobial options were classified from the results of susceptibility testing using the BACH classification of long bone osteomyelitis as either Ax (unknown or culture negative), A1 (good options available) or A2 (limited options available). The cultures and susceptibility of pre-referral microbiology were compared to the new intra-operative sampling results. In addition, an association between previous osteomyelitis excision and antimicrobial options were investigated.Introduction
Materials and Methods
Bone and joint infections are a serious complication of trauma, surgery and soft tissue infections. However, there are few data presenting patient reported outcome measures for osteomyelitis. A recently proposed method for classification of osteomyelitis, BACH, stratifies patients into ‘uncomplicated’ and ‘complex’, based on four key inter-disciplinary components: Seventy-one patients with long-bone osteomyelitis, confirmed using a validated composite protocol, were included. Patients received a single-stage procedure at a specialist bone infection unit. Euro-Qol EQ-5D-3L questionnaires and Visual Analogue Scores (VAS) (0–100) were collected prospectively at baseline, 14 days, 6 weeks, 4 months and 1 year post-operatively. The EQ-5D-3L index score, a composite measure of performance of daily activities, was calculated from the 5 domains of the EQ-5D-3L. BACH was applied retrospectively by two independent clinicians blinded to all patient outcomes.Aim
Method
This study quantified changes in the microbiology of osteomyelitis in a single specialist centre within the UK. The rate of infection with multi-drug-resistant (MDR) bacteria was measured over a ten year period in 388 patients. Patients with confirmed osteomyelitis who received curative surgery from 2013–2017 were included (n=222). Microbiology was compared to patients from a cohort between 2001–2004, using the same diagnostic criteria (n=166).1 The proportion of MDR bacterial pathogens2 from deep tissue culture in these cohorts were compared. Pathogens were analysed according to aetiology and the presence of metal-work.Aim
Method
