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Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_14 | Pages 9 - 9
10 Oct 2023
Aithie J Robinson P Butcher R Denton M Simpson A Messner J
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Patellofemoral instability (PFI) is a common cause of knee pain and disability in the paediatric population. Patella alta, lateralised tibial tubercle, medial patellofemoral ligament (MPFL) deficiency, genu valgum and trochlear dysplasia are well known risk factors.

A prospective database was created including patients referred through our physiotherapy pathway following first-time patella dislocation. Patella alta and lateralisation of the tibial tuberosity was treated with a Fulkerson-type tibial tubercle osteotomy(TTO). Medial patellofemoral ligament was reconstructed using quads tendon autograft pull-down technique. A modified Sheffield protocol was used postoperatively allowing weightbearing in a hinged knee brace.

Forty patients were identified with 8 patients having bilateral presentations. Male to female ratio was 12:28 with an age range of 4–17 years. Eight patients had congenital PFI, five patients acquired PFI through traumatic patella dislocation and twenty-seven patients developed PFI from recurrent dislocations. Structural abnormalities were found in 38(95%) of patients. Patella alta (Caton-Deschamps index >1.2) was identified in 19(47%) patients, genu valgum in 12(30%) patients, increased tibial tubercle-trochlear groove distance(TT-TG>20mm) was present in 9(22.5%) patients and persistent femoral anteversion(> 20 deg) in 7(17%) patients.

Eight patients were treated with TTO and MPFL reconstruction, three patients with MPFL reconstruction alone and five patients had guided growth for genu valgum correction. Ten patients are awaiting surgery. No postoperative patients had recurrence of PFI at their latest follow up.

PFI is a common problem in the adolescent paediatric population with identifiable structural abnormalities. Correcting structural pathology with surgery leads to predictable and safe outcomes.


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_6 | Pages 2 - 2
1 Jun 2022
Yapp L Clement N Moran M Clarke J Simpson A Scott C
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This study aims to determine the lifetime risk of revision surgery after primary knee arthroplasty (KA).

The Scottish Arthroplasty Project dataset was utilised to identify all patients undergoing primary KA during the period 1998–2019. The cumulative incidence function for revision and death was calculated and adjusted analyses utilised cause-specific Cox regression modelling to determine the influence of patient-factors. The lifetime risk was calculated for patients aged between 45–99 years using multiple decrement lifetable methodology.

The lifetime risk of revision ranged between 32.7% (95% Confidence Interval (CI) 22.62–47.31) for patients aged 45–49 years and 0.63% (95%CI 0.1–4.5) for patients aged over 90 years. Adjusted analyses demonstrated the converse effect of age on revision (Hazard Ratio (HR) 0.5, 95%CI 0.5–0.6) and death (HR 3.5, 95%CI 3.4–3.7). Male sex was associated with increased risks of revision (HR 1.1, 95%CI 1.1–1.2) and death (HR 1.4, 95%CI 1.3–1.4). Patients with inflammatory arthropathy had a higher risk of death (HR 1.7, 95%CI 1.7–1.8), but were less likely to be revised (HR 0.85, 95%CI 0.74–0.98) than those treated for osteoarthritis. Patients with greater number of comorbidities and greater levels of socio-economic deprivation were at increased risk of death, but neither increased the risk of revision.

The lifetime risk of revision knee arthroplasty varies depending on patient sex, age at surgery and underlying diagnosis. Patients aged between 45 and 49 years have a one in three probability of revision surgery within their lifetime. Conversely, patients aged 90 years or over were very unlikely to experience revision.


Orthopaedic Proceedings
Vol. 101-B, Issue SUPP_1 | Pages 1 - 1
1 Jan 2019
Tsang S Gwynne P Gallagher M Simpson A
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Staphylococcus aureus is responsible for 60–70% infections of surgical implants and prostheses in Orthopaedic surgery, costing the NHS £120–200 million per annum. Its ability to develop resistance or tolerance to a diverse range of antimicrobial compounds, threatens to halt routine elective implant surgery. One strategy to overcome this problem is to look beyond traditional antimicrobial drug therapies and investigate other treatment modalities. Biophysical modalities, such as ultrasound, are poorly explored, but preliminary work has shown potential benefit, especially when combined with existing antibiotics.

Using a methicillin-sensitive S. aureus reference strain and the dissolvable bead assay, biofilms were challenged by a low-intensity ultrasound (1.5MHz, 30mW/cm2, pulse duration 200µs/1KHz) for 20 minutes and gentamicin. The outcome measures were colony-forming units/mL (CFU/mL) and the minimum biofilm eradication concentration (MBEC) of gentamicin. The mean number of S. aureus within control biofilms was 1.04 × 109 CFU/mL. There was no clinically or statistically significant (p=0.531) reduction in viable S. aureus following ultrasound therapy alone. The MBEC of gentamicin for this S. aureus strain was 256 mg/L. The MBEC of gentamicin with the addition of ultrasound was 64mg/L. Further studies confirmed that the mechanism of action was due to incomplete disruption of the extracellular matrix with subsequent metabolic stimulation of the dormant biofilm-associated bacteria due to increased nutrient availability and oxygen tension.

Low intensity pulsed ultrasound was associated with a 4-fold reduction in the effective biofilm eradication concentration of gentamicin; bringing the MBEC of gentamicin to within clinically achievable concentrations.


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_8 | Pages 7 - 7
1 May 2018
Tsang S Mills L Frantzias J Baren J Keating J Simpson A
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Aim

The aim of this study was to determine whether the absence of periosteal reaction on plain radiographs was predictive of exchange nail failure in lower limb diaphyseal fracture non-unions.

Methods

A consecutive cohort of 20 femora and 35 tibiae undergoing exchange nailing for diaphyseal aseptic (n=39) and septic (n=16) fracture non-union at a single centre from 2003 to 2010. Multiple causes of non-union were found in 29 patients (53%) with infection present in 16 cases (29.1%). Of this cohort 49 fracture non-unions had complete radiographic records (19 femora and 30 tibiae) allowing evaluation of the periosteal callus. The primary outcome was the number of number of revision procedures required to achieve union. Failure was defined was as the requirement of >two revision procedures to achieve union.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_19 | Pages 3 - 3
1 Nov 2017
Tsang S McHugh M Guerendiain D Gwynne P Boyd J Walsh T Laurenson I Templeton K Simpson A
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Nasal carriers of methicillin sensitive Staphylococcus aureus (MSSA) have an increased risk for health-care associated infections. There is currently no national screening policy for the detection of MSSA in the UK. This study aimed to: evaluate the diagnostic performance of molecular and culture techniques in MSSA screening, determine the cause of any discrepancy between the diagnostic techniques, and model the potential effect of different diagnostic techniques on MSSA detection in orthopaedic patients. Paired nasal swabs for PCR assay and culture of S. aureus were collected from a study population of 273 orthopaedic outpatients due to undergo joint replacement surgery.

The prevalence of MSSA nasal colonisation was found to be between 22.4–35.6%. The current standard direct culturing methods for detecting S. aureus significantly underestimated the prevalence (p=0.005), failing to identify its presence in ∼1/3 of patients undergoing joint replacement surgery.

Modelling these results to national surveillance data, it was estimated that 800–1200 MSSA surgical site infections could be prevented annually in the UK by using alternative diagnostic methods to direct culture in pre-operative MSSA screening and eradication programmes.


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_19 | Pages 5 - 5
1 Nov 2017
Mackenzie S Wallace R White T Murray A Simpson A
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Kirschner wires are commonly used in paediatric fractures, however, the requirement for removal and the possibility of pin site infection provides opportunity for the development of new techniques that eliminate these drawbacks. Bioabsorbable pins that remain in situ and allow definitive closure of skin at the time of insertion could provide such advantages.

Three concurrent studies were performed to assess the viability of bioabsorbable pins across the growth plate. (1) An epidemiological study to identify Kirschner wire infection rates. (2) A mechanical assessment of a bioabsorbable pin compared to Kirschner wires in a simulated supracondylar fracture. (3) The insertion of the implants across the physis of sheep to assess effects of the bioabsorbable implant on the growth plate via macroscopic, pathohistological and micro-CT analysis.

An infection rate of 8.4% was found, with a deep infection rate of 0.4%. Mechanically the pins demonstrated comparable resistance to extension forces (p=) but slightly inferior resistance to rotation (p=). The in vivo component showed that at 6 months: there was no leg length discrepancy (p=0.6), with micro-CT evidence of normal physeal growth without tethering, and comparable physeal width (p=0.3).

These studies combine to suggest that bioabsorbable pins do not represent a threat to the growth plate and may be considered for physeal fracture fixation.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_17 | Pages 2 - 2
1 Dec 2015
Murray I Gonzalez Z West C Miranda-Carboni G Simpson A Corselli M Péault B
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Mesenchymal stem cells (MSCs) reside around blood vessels in all organs. This reservoir of progenitors can be ‘recruited’ in response to injury. The ability to manipulate stem cells therapeutically within injured tissue provides an attractive alternative to transplantation. Stem cells are regulated by neighbouring cells. We hypothesized that endothelial cells (ECs) influence MSC differentiation into bone and fat.

MSCs were sorted from fat using fluorescent activated sorting. Their capacity to differentiate into bone, fat and cartilage was used to confirm MSC phenotype. MSCs and ECs were cultured in two-dimensions (standard culture dishes) and three-dimensions (vascular networks suspended in gel). Cocultures were exposed to osteogenic and adipogenic media. The role of EC-released factors on MSC differentiation was determined using a system in which cells share media but do not contact. Wnt pathway modulators were used to investigate the role of Wnt signalling.

MSCs differentiated into bone, fat and cartilage. MSCs and ECs integrated in two- and three-dimensions. MSCs and ECs formed vessel-like structures in three-dimensions. When cultured with ECs, MSC differentiation to bone was accelerated while differentiation to fat was inhibited. This effect on osteogenesis was maintained when cells shared media but did not contact. Coculture with Wnt modulators confirmed that this effect is in part, mediated through Wnt signalling.

Our data suggest that ECs influence MSC differentiation. Therapeutic targeting of EC-MSCs signalling may enable manipulation of MSCs in vivo avoiding the need for cell transplantation. This could enable trauma and orthopaedic patients who have healthy resident stem cells to self-repair.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_17 | Pages 7 - 7
1 Dec 2015
Clement N MacDonald D Burnett R Simpson A Howie C
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This study assessed whether patient satisfaction with their hospital stay influences the early outcome of total knee replacement (TKR).

During a five year period patients undergoing primary TKR at the study centre had prospectively outcome data recorded (n=2264). Patients with depression (p=0.04) and worse mental wellbeing (p<0.001), according to the short form (SF)-12, were more likely to be dissatisfied with their hospital stay. Decreasing level of satisfaction with their hospital stay was associated with a significantly worse post-operative OKS (p<0.001) and SF-12 score (p<0.001). Multivariable regression analysis confirmed that the patients perceived level of satisfaction with their hospital stay was an independent predictor of change in the OKS (p<0.001) and SF-12 score (p<0.001) after adjusting for confounding variables. Patient satisfaction with their TKR was significantly influenced by their hospital experience, decreasing from 96% in those with an excellent experience to 42% in those with a poor experience. Food, staff/care, and the hospital environment were the most frequent reasons of why patients rated their hospital experience as fair or poor.

A patient's perception of their inpatient hospital experience after surgery is an important modifiable predictor of early functional outcome and satisfaction with TKR.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_4 | Pages 8 - 8
1 May 2015
Tsang S Mills L Frantzias J Baren J Keating J Simpson A
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The aim of this study was to identify risk factors for failure of exchange nailing for femoral diaphyseal fracture non-unions. The study cohort comprised 40 patients with femoral diaphyseal non-unions treated by exchange nailing. The main outcome measures were union, number of secondary fixation procedures required to achieve union and time to union. Univariate analysis and multiple regression were used to identify risk factors for failure to achieve union.

The mean age of the patients at exchange nail surgery was 37 years. The median time to exchange nailing from primary fixation was 8.4 months. Multiple causes for non-union were found in 14 (35.0%) cases, with infection present in 12 (30.0%) patients. Further exchange procedures were required in nine (22.5%) cases, one patient (2.5%) required the use of another fixation modality, to achieve union. Union was ultimately achieved in 35 (94.5%) patients. The median time to union was 9.4 months after the exchange nail procedure. Univariate analysis confirmed that cigarette smoking and infection were predictive of failure (p<0.05). Multi-regression analysis found that Gustilo-Anderson grade, presence of dead bone or a gap and infection were predictive of exchange nail failure (p <0.05).

Exchange nailing is an effective treatment for aseptic femoral diaphyseal fracture non-union. Patients with infection required more than one procedure. Smoking, infection and the presence of dead-bone or a gap at the fracture site were associated with an increased risk of further fixation surgery.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_4 | Pages 12 - 12
1 May 2015
Murray I Hardy W West C Zhang X James A Soo C Simpson A Peault B
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Adipose tissue is an attractive source of mesenchymal stem cells (MSCs) as it is largely dispensable and readily accessible through minimally invasive procedures such as lipoaspiration. Until recently MSCs could only be isolated in a process involving ex-vivo culture. Pericytes (CD45−, CD146+, and CD34−) and adventitial cells (CD45−, CD146−, CD34+) represent two populations of MSCs (collectively termed perivascular stem cells or PSCs) that can be prospectively purified using fluorescence activated cell sorting (FACS). We performed FACS on lipoaspirate samples from n=129 donors to determine the frequency and yield of PSCs and to establish patient and processing factors that influence yield.

The mean number of stromal vascular fraction (SVF) cells from 100ml of lipoaspirate was 37.8×106. Within the SVF, mean cell viability was 82%, with 31.6% of cells being heamatopoietic (CD45+). Adventitial cells and pericytes represented 31.6% and 7.9% of SVF cells respectively. As such, 200ml of lipoaspirate would theoretically yield 24.5 million MSCs –a sufficient number to enable point-of-care delivery for use in several orthopaedic applications. The yield and prevalence of PSCs were minimally affected by donor age, sex and BMI. Storing lipoaspirate samples for up to 72 hours prior to processing had no significant deleterious effects on MSC yield or viability.

Our study confirms that pure populations of MSC-precursors (PSCs) can be prospectively isolated from adipose tissue, in sufficient quantities to negate the necessity for culture expansion while widening possible applications to include trauma, where a time delay between extraction and implantation excludes their use.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_4 | Pages 11 - 11
1 May 2015
Clement N Keenan G Marsh D Nayagam D Atkins R Simpson A
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We conducted a multicentre two arm double blind randomised controlled trial to assess efficacy of pulsed ultrasound for accelerating the rate of bone healing. Sixty-two skeletally mature adults undergoing limb lengthening, of between 2.5cm to 10cm by distraction osteogenesis, at the proximal tibia using an Ilizarov frame were randomised to either an active or a placebo (control) ultrasound device.

Primary outcome measure was time ready for removal of frame after adjusting for distraction length (days/cm) for both intension to treat (ITT) and per protocol (PP) patients. The time at which the frame was removed was determined by the maturation of the regenerate bone. Secondary outcomes were return to weight bearing and covariates affecting time to frame removal.

The baseline characteristics of the two groups were well balanced, and 90% of patients were managed and followed up as PP. There was no difference in the time to frame removal between the two groups for the ITT (5.0days/cm, p=0.23) or the PP (10.1days/cm, p=0.054). There was no difference in return to weight bearing between the two groups, after adjusting for distraction length, for the ITT or PP patients (p>0.5). Smoking was the only covariate identified to increase the frame removal time (hazard ratio 0.46, 95% confidence interval 0.22 to 0.96; p=0.04).

This trial demonstrated no difference in bone healing between those who underwent pulsed ultrasound and those who did not. Smoking was observed to have a significant inhibitory effect on bone healing.


Orthopaedic Proceedings
Vol. 97-B, Issue SUPP_5 | Pages 11 - 11
1 May 2015
Simpson A Clement N Keenan G Nayagam S Atkins R Marsh D
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Objective:

To assess efficacy of pulsed ultrasound for accelerating regenerate consolidation.

Design:

A multicentre two arm patient and assessor double blind RCT


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_14 | Pages 1 - 1
1 Oct 2014
Tsang S Mills L Frantzias J Baren J Keating J Simpson A
Full Access

The aim of this study was to identify risk factors for failure of exchange nailing in tibial diaphyseal fracture non-unions. The cohort comprised 99 tibial diaphyseal fracture non-unions treated by exchange nailing. The mean age of the patients at exchange nail surgery was 36 years. The median time from primary fixation to exchange nailing was 6.4 months. The main outcome measures were union, number of secondary fixation procedures required to achieve union and time to union. Univariate analysis and multiple regression were used to identify risk factors for failure to achieve union.

Multiple causes for non-union were found in 31.3% cases, with infection present in 32.3%. Further exchange procedures were required in 35.4%, 7.1% required the use of other fixation modalities. Union was ultimately achieved in 97.8%. The median time to union was 8.7 months. Univariate analysis revealed that cigarette smoking, an atrophic pattern of non-union and infection were predictive for failure of exchange nailing (p<0.05). Multi-regression analysis found that only infection was statistically significantly predictive (p<0.05) of exchange nail failure.

Exchange nailing is an effective treatment for tibial diaphyseal non-unions even in the presence of infection. Smoking, atrophic pattern of non-union and infection are associated with an increased risk of further fixation surgery.


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_10 | Pages 17 - 17
1 Feb 2013
Smith I Milto K Doherty C Amyes S Simpson A Hall A
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Staphylococcus aureus is a highly virulent pathogen and is implicated in approximately 50% of cases of septic arthritis. Studies investigating other S. aureus-related infections have suggested that alpha (Hla), beta (Hlb) and gamma (Hlg) toxins are key virulence factors. In particular, the ‘pore-forming’ alpha toxin is believed to be most potent. In this study, we have assessed the influence of alpha toxin on in situ chondrocyte viability.

Osteochondral explants were harvested from the metacarpophalangeal joints of 3-year-old cows and placed into flasks containing Dulbecco's Modified Eagle's Medium. The flasks were then inoculated with the following isogenic ‘knockout’ strains of S. aureus: DU5946 (Hla+Hlb-Hlg-) or DU1090 (Hla-Hlb+Hlg+).

The explants were incubated (37°C) and stained after 18, 24 and 40hrs with chloromethylfluorescein di-acetate and propidium iodide, labelling living chondrocytes green and dead cells red, respectively. Axial sections were imaged by confocal microscopy and the percentage cell death obtained using Volocity 4 software.

The alpha toxin-producing S. aureus caused rapid cell death, with 24.8+/−3.7% at 18hrs and 44.6+/−7.2% at 24hrs. At 40hrs, there was significantly more chondrocyte death (87.4+/−3.6%; p<0.001) compared to the alpha toxin knockout strain (4.1+/−1.7%; means +/− SEM; n=4).

In situ chondrocyte viability was significantly compromised by alpha toxin, with beta and gamma toxins having minimal effect. Further work will clarify the exact mechanism through which this important toxin induces chondrocyte death. Thereafter, it is hoped that targeted treatments can be developed to reduce the extent of cartilage destruction during, and after, an episode of septic arthritis.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXIII | Pages 11 - 11
1 Jul 2012
Smith I Cyrulik K Amyes S Simpson A Hall A
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In some centres, serial bedside aspirations, in association with intravenous antibiotics, are still an accepted treatment for septic arthritis (Mathews, Postgraduate Medical Journal, 2008). However, there is a risk that bacterial products remain in the joint, even when the bacteria have been destroyed. We have conducted a study to ascertain whether bacterial products alone have an effect on in situ chondrocyte viability.

A hip aspirate (25μl), containing Staphylococcus aureus, from a patient with septic arthritis was added to 5ml culture medium and incubated (37°C) for 48hrs. The solution was then centrifuged (3400g for 10mins) and the supernatant removed.

Cartilage explants were harvested from a bovine metacarpophalangeal joint, placed into the bacterial supernatant and incubated at 37°C. Explants were removed at hourly intervals over a 6-hour period and stained with the fluorescent probes chloromethylfluorescein di-acetate (10μM) and propidium iodide (10μM) to label living chondrocytes green and dead cells red respectively. Following imaging of cartilage by confocal microscopy, the percentage cell death at each time point was obtained using Volocity 4 software.

Chondrocyte death increased markedly with time: 0.04% at 2hrs, 28% at 4hrs and 39% at 6hrs.

This study shows that bacterial products rapidly penetrate the cartilage matrix and have a damaging effect on in situ chondrocyte viability. Further work will clarify the contributions made by the various toxic components in the culture supernatant, but these data support the need to remove the bacteria and their products aggressively as part of the treatment of septic arthritis.


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_V | Pages 3 - 3
1 Mar 2012
Jenkins PJ Teoh K Simpson PM Dave J Simpson A Breusch S
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Clostridium difficile is associated with a range of gastrointestinal disorders ranging from diarrhoea to toxic megacolon. Alteration of the normal gut flora by antibiotics is a key predisposing factor. Although antibiotic prophylaxis is routinely administered during joint replacement surgery, there has been controversy about both type and duration of prophylaxis. The primary aim of this study was to determine the incidence of C. diff associated disease (CDAD) following hip and knee replacement and to investigate potential risk factors.

A laboratory database was interrogated to identify patients developing CDAD after hip or knee replacement from January 2006 to December 2008. A database of arthroplasty patients was used to identify a control group of patients without CDAD to compare the effects of prescription of antibiotics for reasons other prophylaxis of deep infection, comorbidity and the use of gastroprotective agents.

Eight patients developed CDAD. There were 1.7 cases of CDAD per 1000 joint replacements. Patients developing CDAD were more likely to have been prescribed additional antibiotics (p=0.047). There were no differences in the use of gastroprotective agents (p=0.703). A trial of a new prophylaxis regime would require 43,198 patients in each arm to show a reduction to 1 case per 1000 procedures.

Cefuroxime based antibiotic prophylaxis is safe in patients undergoing elective joint replacement. Extremely large studies would be required to show marginal clinical benefits of new regimes. One prophylaxis policy will not suit all orthopaedic patient groups or procedures.