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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_17 | Pages 3 - 3
24 Nov 2023
Dinh A Chatillon ED Ho R McNally M Dudareva M Scarborough M Jesuthasan G Escolà-Vergé L Lora-Tamayo J Mancheño-Losa M Thill P Giordano G Fourcade C Duran C Bonnet E Hascoet JL
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Aim

Prosthetic joint infection (PJI) due to Candida spp. is a severe complication of arthroplasty but is little reported. This study describes Candida PJI epidemiology, management, and outcome.

Method

We performed a retrospective, observational multinational study with support of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Patients diagnosed with PJI due to Candida spp. between 1990 and 2021 were included. Demographic, clinical, laboratory, imaging, medical/surgical treatment, and outcome data were collected within a standardized database. Treatment failure was defined either as a Candida infection recurrence, superinfection, or death due to infection.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 34 - 34
1 Oct 2022
Dudareva M Corrigan R Hotchen A Muir R Scarborough C Kumin M Atkins B Scarborough M McNally M Collins G
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Aim

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.

Methods

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.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 60 - 60
1 Oct 2022
Dudareva M Corrigan R Hotchen A Muir R Sattar A Scarborough C Kumin M Atkins B Scarborough M McNally M Collins G
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Aim

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.

Methods

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 a priori sample size calculation: age, gender, BMI, ASA score, the number of prior operations, immunosuppressive medication, glycosylated haemoglobin (HbA1c), and smoking. Missing data, including systematically missing predictors, were imputed using Multiple Imputation by Chained Equations. Weekly alcohol intake was not included in modelling due to low inter-observer reliability (mean reported intake 12 units per week, 95% CI for mean inter-rater error −16.0 to +15.4 units per week).


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 55 - 55
1 Oct 2022
Hotchen A Kendall J Scarborough M McNally M
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Aim

To assess whether recurrence of PJI and osteomyelitis impacts patient-reported quality of life (QoL).

Method

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.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_10 | Pages 86 - 86
1 Oct 2022
McNally M Ferguson J Scarborough M Ramsden A Stubbs D Atkins B
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Aim

Excision of chronic osteomyelitis (cOM) creates a dead space which must be managed to avoid early recurrence of infection. Systemic antimicrobials cannot penetrate this space in high concentration so local therapy has become an attractive adjunct to surgery. This study presents the mid- long-term results of local therapy with gentamicin in a bioabsorbable ceramic carrier.

Method

A prospective series of 100 patients with Cierny & Mader Types III and IV cOM, affecting 105 bones, were treated with a single stage procedure, including debridement, deep tissue sampling, local and systemic antimicrobials, stabilization and immediate skin closure. cOM was confirmed with strict diagnostic criteria. Patients were followed up for a mean of 6.05 years (range 4.2–8.4 years).


The Bone & Joint Journal
Vol. 104-B, Issue 9 | Pages 1095 - 1100
1 Sep 2022
McNally MA Ferguson JY Scarborough M Ramsden A Stubbs DA Atkins BL

Aims

Excision of chronic osteomyelitic bone creates a dead space which must be managed to avoid early recurrence of infection. Systemic antibiotics cannot penetrate this space in high concentrations, so local treatment has become an attractive adjunct to surgery. The aim of this study was to present the mid- to long-term results of local treatment with gentamicin in a bioabsorbable ceramic carrier.

Methods

A prospective series of 100 patients with Cierny-Mader Types III and IV chronic ostemyelitis, affecting 105 bones, were treated with a single-stage procedure including debridement, deep tissue sampling, local and systemic antibiotics, stabilization, and immediate skin closure. Chronic osteomyelitis was confirmed using strict diagnostic criteria. The mean follow-up was 6.05 years (4.2 to 8.4).


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_15 | Pages 44 - 44
1 Dec 2021
Dudareva M Vallis C Dunsmure L Scarborough M
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Aim

Fungal orthopaedic infections most commonly affect people with complex surgical histories and existing comorbidities. Recurrence and re-infection rates are high, even with optimal surgical and systemic antifungal treatment. AmBisome liposomal amphotericin B has been suggested for local antifungal therapy, as an adjunctive treatment for fungal osteoarticular infections. Few case series have examined its clinical use when combined with polymethylmethacrylate cement PMMA), or with absorbable local antibiotic carriers.

We aimed to evaluate the clinical use of local antifungal therapy with AmBisome liposomal amphotericin B (ABlaB), including tolerated doses, serious adverse events, and treatment outcomes.

Method

A retrospective cohort of all patients treated with local antifungal therapy with ABlaB between January 2016 and January 2021 in a specialist orthopaedic hospital was identified using pharmacy records.

Renal function, serious adverse events during treatment, surgical outcomes including spacer fracture and infection recurrence, were identified from electronic clinical records. The project was approved by the Institutional Review Board (clinical audit 6871).


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_14 | Pages 60 - 60
1 Dec 2019
Hotchen A Dudareva M Ferguson J Rombach I Scarborough M McNally M
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Aim

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: Bone involvement, Anti-microbial options, soft-tissue Coverage and Host status. We aim to correlate the classification severity with patient reported outcomes following osteomyelitis surgery.

Method

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.


The Bone & Joint Journal
Vol. 101-B, Issue 3 | Pages 246 - 252
1 Mar 2019
Iwata E Scarborough M Bowden G McNally M Tanaka Y Athanasou NA

Aims

The aim of this study was to determine the diagnostic utility of histological analysis in spinal biopsies for spondylodiscitis (SD).

Patients and Methods

Clinical features, radiology, results of microbiology, histology, and laboratory investigations in 50 suspected SD patients were evaluated. In 29 patients, the final (i.e. treatment-based) diagnosis was pyogenic SD; in seven patients, the final diagnosis was mycobacterial SD. In pyogenic SD, the neutrophil polymorph (NP) infiltrate was scored semi-quantitatively by determining the mean number of NPs per (×400) high-power field (HPF).


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_17 | Pages 15 - 15
1 Dec 2018
Dudareva M Barrett L Morgenstern M Oakley S Scarborough M Atkins B McNally M Brent A
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Aim

Current guidelines for the diagnosis of prosthetic joint infection (PJI) recommend collecting 4–5 independent tissue specimens, with isolation of indistinguishable organisms from two or more specimens. The same principle has been applied to other orthopaedic device-related infections (DRI) including fracture-related infections. However there are few published data validating this approach in DRI other than PJI. We evaluated the performance of different diagnostic cutoffs and varying numbers of tissue specimens for microbiological sampling in fracture-related infections.

Method

We used standard protocols for tissue sample collection and laboratory processing, and a standard clinical definition of fracture-related infection. We explored how tissue culture sensitivity and specificity varied with the number of tissue specimens obtained; and with the number of specimens from which an identical isolate was required (diagnostic cutoff). To model the effect of the number of specimens taken we randomly sampled n specimens from those obtained at each procedure, excluding procedures from which less than n specimens were collected, and calculated sensitivity and specificity based on this sample. For each value of n we repeated this process 100 times to estimate the mean sensitivity and specificity for n specimens.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 9 - 9
1 Dec 2017
Li HK Rombach I Zambellas R Warren S Mack D Hopkins S Hems-ley C Atkins B Rogers M McNally M Scarborough M
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Aim

Management of bone and joint infection can be technically complex and often requires a prolonged course of antibiotics. Traditionally, bone and joint infection management utilises nurse-led outpatient parenteral antibiotic therapy (OPAT) where adherence is unlikely to be an issue. However, with increasing evidence in favour of oral therapy, the question of adherence merits further consideration. We describe the adherence of both oral (PO) and self-administered intravenous (IV) antibiotics in the treatment of bone and joint infection using paper questionnaires (8-item Modified Morisky Adherence Score (MMAS)) and, in a subset of participants, electronic pill containers (Medication Event Monitoring Systems*).

Method

All eligible participants enrolled in the OVIVA trial (2010–2015) were randomised to six weeks of either PO or IV antibiotic treatment arms. Self-administering patients were followed up with questionnaires at day 14 and 42. A subset of PO participants was also given the medication event monitoring system* in order to validate the adherence questionnaires. The results were correlated with treatment failures at one-year follow-up.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 42 - 42
1 Dec 2017
Scarborough M Li HK Rombach I Zambellas R Walker S Kumin M Lipsky BA Hughes H Bose D Warren S Geue C McMeekin N Woodhouse A Atkins B McNally M Berendt T Angus B Byren I Thwaites G Bejon P
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Aim

Current standard of care in the management of bone and joint infection commonly includes a 4–6 week course of intravenous (IV) antibiotics but there is little evidence to suggest that oral antibiotic therapy results in worse outcomes. The primary objective was to determine whether oral antibiotics are non-inferior to IV antibiotics in this setting.

Method

This was a parallel group, randomised (1:1), open label, non-inferiority trial across twenty-six NHS hospitals in the United Kingdom. Eligible patients were adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least six weeks of antibiotics and who had received ≤7 days of IV therapy from the date of definitive surgery (or the start of planned curative treatment in patients managed non-operatively). Participants were randomised to receive either oral or IV antibiotics for the first 6 weeks of therapy. Follow-on oral therapy was permitted in either arm. The primary outcome was the proportion of participants experiencing definitive treatment failure within one year of randomisation. The non-inferiority margin was set at 7.5%.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_22 | Pages 43 - 43
1 Dec 2017
Alvand A Li HK Rombach I Zambellas R Kendrick B Taylor A Atkins B Bejon P McNally M Scarborough M
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Aim

To assess the influence of route of antibiotic administration on patient-reported outcome measures (PROMS) of individuals treated for hip and knee infections in the OVIVA multi-centre randomised controlled trial.

Method

This study was designed to determine whether oral antibiotic therapy is non-inferior to intravenous (IV) therapy when given for the first six weeks of treatment for bone and joint infections. Of the 1054 participants recruited from 26 centres, 462 were treated for periprosthetic or native joint infections of the hip or knee. There were 243 participants in the IV antibiotic cohort and 219 in the oral cohort. Functional outcome was determined at baseline through to one year using the Oxford Hip/Knee Score (OHS/OKS) as joint-specific measures (0 the worse and 48 the best). An adjusted quantile regression model was used to compare functional outcome scores.


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_23 | Pages 83 - 83
1 Dec 2016
McNally M Ferguson J Diefenbeck M Lau A Stubbs D Scarborough M Ramsden A Atkins B
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Aim

Eradication of infection in chronic osteomyelitis requires effective dead space management after debridement. Residual bacteria in biofilm may be resistant to normal levels of systemic antibiotic penetrating bone and will contribute to recurrence of osteomyelitis. This study evaluated a new antibiotic-loaded biocomposite in the eradication of chronic infection from bone defects.

Patients and Method

We report a prospective study of 100 patients with Cierny and Mader types III and IV chronic osteomyelitis, in 105 bones. Osteomyelitis followed open fracture or ORIF of closed fractures in 71%. Nine had concomitant septic arthritis. 80% had comorbidities (Cierny-Mader Class B hosts). Ten had infected non-unions.

All patients were treated by a multidisciplinary team with a single-stage protocol including; debridement, multiple sampling, culture-specific systemic antibiotics, stabilisation, dead space filling with Cerament G™ and immediate primary skin closure.

Stabilisation was required in 21 cases and 5 required joint fusion as part of the initial surgery. Plastic surgical skin closure was needed in 23 cases (18 free flaps).

Patients were followed up for a minimum of one year (mean 19.5 months; 12–34).


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_23 | Pages 4 - 4
1 Dec 2016
Alvand A Grammatopoulos G de Vos F Scarborough M Athanasou N Kendrick B Price A Gundle R Whitwell D Jackson W Taylor A Gibbons M
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Introduction

The burden of peri-prosthetic joint infection (PJI) following hip and knee surgery is increasing. Endoprosthetic replacement (EPR) is an option for management of massive bone loss resulting from infection around failed lower limb implants.

Aims

To determine clinical outcome of EPRs for treatment of PJI around the hip and knee joint.


The Bone & Joint Journal
Vol. 98-B, Issue 9 | Pages 1289 - 1296
1 Sep 2016
McNally MA Ferguson JY Lau ACK Diefenbeck M Scarborough M Ramsden AJ Atkins BL

Aims

Chronic osteomyelitis may recur if dead space management, after excision of infected bone, is inadequate. This study describes the results of a strategy for the management of deep bone infection and evaluates a new antibiotic-loaded biocomposite in the eradication of infection from bone defects.

Patients and Methods

We report a prospective study of 100 patients with chronic osteomyelitis, in 105 bones. Osteomyelitis followed injury or surgery in 81 patients. Nine had concomitant septic arthritis. 80 patients had comorbidities (Cierny-Mader (C-M) Class B hosts). Ten had infected nonunions.

All patients were treated by a multidisciplinary team with a single-stage protocol including debridement, multiple sampling, culture-specific systemic antibiotics, stabilisation, dead space filling with the biocomposite and primary skin closure.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_16 | Pages 19 - 19
1 Dec 2015
Li H Finney J Kendall J Shaw R Scarborough M Atkins B Ramsden A Stubbs D Mcnally M
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Bone and joint infections are not only common but their management can be technically complex. They carry significant healthcare costs and are a daunting experience for patients [1]. Frequently, multiple operations are required in order to treat the infection. Each surgical intervention usually results in greater bone loss, worsening skin and soft tissue scarring and increasingly diverse and resistant micro- organisms [2].

Specialist bone infection units involving highly integrated orthopaedic and plastic surgery, as well as infection physicians, may improve patient outcomes [3–4]. However, it is difficult to determine the hierarchy of factors contributing to outcome of treatment. This problem is confounded by a lack of structured, prospective data collection in many units around the world.

In 2014, we designed a modular database which allows collection of patients’ details, components of the disease, the treatment, microbiology, histology, clinical outcome and patient-reported outcome measures (PROMS). The registry was implemented in November 2014 and has already demonstrated its function as a Hospital-wide service evaluation tool.

Over 200 patients have been referred to the unit and their baseline demographic information registered. Their progress through the bone infection unit patient pathway is prospectively monitored with use of the registry and data collection ongoing. We aim to present the preliminary clinical outcomes of these 200 patients including surgical procedures performed, key microbiology results, antibiotic treatment regimens and patient reported outcomes.

Our goal is to demonstrate that a bone infection registry is an integral part of infection management clinical practice. It can be used for designing service provision, assist in allocating healthcare resources and expand the evidence base for specialist bone infection units in managing complex orthopaedic infections.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_16 | Pages 21 - 21
1 Dec 2015
Mcnally M Ferguson J Kendall J Dudareva M Scarborough M Stubbs D
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To evaluate the clinical outcome of three different local antibiotic delivery materials, used as bone defect fillers after excision of chronic osteomyelitis.

We reviewed all patients receiving Collagen Fleece with Gentamicin (Septocoll E)(n=74), Calcium Sulphate with Tobramycin pellets (Osteoset T)(n=166) or Calcium Sulphate/Hydroxyapatite biocomposite with Gentamicin (Cerament G)(n=73) for dead space filling after resection of C-M Stage III and IV chronic osteomyelitis. Data was collected on patient comorbidities, operation details, microbiology, postop complications and need for plastic surgery or external fixation. All operations were performed by two surgeons. All patients had similar systemic antibiotic therapy and rehabilitation.

Primary outcomes were recurrence rate, fracture rate and wound leakage rate.

All three groups had very similar mean age and range, microbiological cultures, need for free muscle flaps or local flaps, proportion of femur, tibia and upper limb bones and use of external fixation. There were small differences in the proportion of C-M Class B hosts and anatomic Type IV cases, between the groups. All patients were followed up for at least one year. Mean follow-up was 1.75 years for Septocoll E, 1.96 years for Osteoset T and 1.78 years for Cerament G.

After surgery, there were fewer prolonged wound leaks with Cerament G (leakage persisting for more than 2 weeks). Fracture rates and infection recurrence were twice as common with Osteoset T compared with Cerament G at between one and two years after operation (see Table).

The use of a biocomposite material delivering local aminoglycoside was associated with lower recurrence rates and few wound problems, compared with collagen or calcium sulphate alone. This may reflect the higher levels of antibiotic in the defect and controlled release profile. The improved recurrence rate was despite a higher percentage of compromised Class B hosts.


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 191 - 191
1 Mar 2006
Casanova J Reith J Scarborough M Enneking W
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Background: A variety of molecular markers related to survival, have been studied in a variety of human neoplasms, particularly in carcinomas, but their significance in osteosarcoma patients is largely unknown. The purpose of this archival study was to determine if there is a correlation between their expression and disease-free and overall survival for patients with osteosarcoma.

Materials and Methods: 93 patients with stage IIB osteosarcomas originating around the knee (distal femur and proximal tibia)were studied. Tumors were evaluated with antibodies to Bcl-2, p53, Fas, Fas L, CD44s, CD44v6, and P-glycoprotein using standard avidinbiotin complex methods. Expression of the various antigens was statisticaly compared to disease-free and overall survival.

Results: Fas (p< 0.05) and Cd44v6 (p< 0.03), were significant and related with the purpose of study; P-glycoprotein was near and the others with no significance.

Conclusions: Fas appears to have a “protective” function in osteosarcoma, probably by allowing tumor cells to proceed through apoptosis pathway to cell death. Although CD44v6, a vascular adhesion molecule, was identified in only 14% of the total cases, its expression correlated with subsequent development of metastases and death (11 of the 13 patients developed pulmonary metastases dying of disease). Although P-glycoprotein did not reach significance, there was a trend toward death from disease in patients expressing it.