What is the role of ultrasound in fracture management?: Diagnosis and therapeutic potential for fractures, delayed unions, and fracture-related infection.

OBJECTIVES: The aim of this study was to review the current evidence and future application for the role of diagnostic and therapeutic ultrasound in fracture management. METHODS: A review of relevant literature was undertaken, including articles indexed in PubMed with keywords "ultrasound" or "sonography" combined with "diagnosis", "fracture healing", "impaired fracture healing", "nonunion", "microbiology", and "fracture-related infection". RESULTS: The use of ultrasound in musculoskeletal medicine has expanded rapidly over the last two decades, but the diagnostic use in fracture management is not routinely practised. Early studies have shown the potential of ultrasound as a valid alternative to radiographs to diagnose common paediatric fractures, to detect occult injuries in adults, and for rapid detection of long bone fractures in the resuscitation setting. Ultrasound has also been shown to be advantageous in the early identification of impaired fracture healing; with the advent of 3D image processing, there is potential for wider adoption. Detection of implant-related infection can be improved by ultrasound mediated sonication of microbiology samples. The use of therapeutic ultrasound to promote union in the management of acute fractures is currently a controversial topic. However, there is strong in vitro evidence that ultrasound can stimulate a biological effect with potential clinical benefit in established nonunions, which supports the need for further investigation. CONCLUSION: Modern ultrasound image processing has the potential to replace traditional imaging modalities in several areas of trauma practice, particularly in the early prediction of impaired fracture healing. Further understanding of the therapeutic application of ultrasound is required to understand and identify the use in promoting fracture healing.Cite this article: J. A. Nicholson, S. T. J. Tsang, T. J. MacGillivray, F. Perks, A. H. R. W. Simpson. What is the role of ultrasound in fracture management? Diagnosis and therapeutic potential for fractures, delayed unions, and fracture-related infection. Bone Joint Res 2019;8:304-312. DOI: 10.1302/2046-3758.87.BJR-2018-0215.R2.

Non-union: Indications for external fixation.

External fixation is currently used as the definitive mode of fracture stabilisation in the management of ˜50% of long-bone non-unions. Distinction between non-union and delayed union is a diagnostic dilemma especially in fractures healing by primary bone repair. This distinction is important, as non-unions are not necessarily part of the same spectrum as delayed unions. The aetiology of a fracture non-union is usually multifactorial and the factors can be broadly categorized into mechanical factors, biological (local and systemic) factors, and infection. Infection is present in ˜40% of fracture non-unions, often after open fractures or impaired wound healing, but in 5% of all non-unions infection is present without any clinical or serological suspicion. General indications for external fixation include clinical scenarios where; 1) percutaneous correction of alignment, or mechanical stimulation of the non-union site is required; 2) fixation of juxta-articular or 'emmental' bone fragments is necessary; and 3) staged bone or soft tissue reconstruction is anticipated. Specific anatomical indications include infected non-unions of the tibia, humerus, and juxta-articular bone. External fixation is an essential tool in the management of fracture non-unions. However, with greater understanding of the outcomes associated with both external and internal fixation the relative indications are now being refined.

The biofilm eradication activity of acetic acid in the management of periprosthetic joint infection.

OBJECTIVES: Periprosthetic joint infection following joint arthroplasty surgery is one of the most feared complications. The key to successful revision surgery for periprosthetic joint infections, regardless of treatment strategy, is a thorough deep debridement. In an attempt to limit antimicrobial and disinfectant use, there has been increasing interest in the use of acetic acid as an adjunct to debridement in the management of periprosthetic joint infections. However, its effectiveness in the eradication of established biofilms following clinically relevant treatment times has not been established. Using an in vitro biofilm model, this study aimed to establish the minimum biofilm eradication concentration (MBEC) of acetic acid following a clinically relevant treatment time. MATERIALS AND METHODS: Using a methicillin-sensitive Staphylococcus aureus (MSSA) reference strain and the dissolvable bead assay, biofilms were challenged by 0% to 20% acetic acid (pH 4.7) for ten minutes, 20 minutes, 180 minutes, and 24 hours. RESULTS: The MBEC of acetic acid was found to be: 15%, 11%, 3.2%, and 0.8% following a ten-minute, 20-minute, 180-minute, and 24-hour treatment, respectively. CONCLUSION: This study found that the MBEC of acetic acid following a 10- or 20-minute treatment time exceeded its safety threshold, making these concentrations unsuitable as a topical debridement adjunct. However, a clinically acceptable concentration (5%) was still found to eliminate 96.1% of biofilm-associated MSSA following a 20-minute treatment time.Cite this article: S. T. J. Tsang, P. J. Gwynne, M. P. Gallagher, A. H. R. W. Simpson. The biofilm eradication activity of acetic acid in the management of periprosthetic joint infection. Bone Joint Res 2018;7:517-523. DOI: 10.1302/2046-3758.78.BJR-2018-0045.R1.

Non-union after plate fixation.

Approximately a third of patients presenting with long-bone non-union have undergone plate fixation as their primary procedure. In the assessment of a potential fracture non-union it is critical to understand the plating technique that the surgeon was intending to achieve at the primary procedure, i.e. whether it was direct or indirect fracture repair. The distinction between delayed union and non-union is a diagnostic dilemma especially in plated fractures, healing by primary bone repair. The distinction is important as nonunions are not necessarily part of the same spectrum as delayed unions. The etiology of a fracture non-union is usually multifactorial and the factors can be broadly categorized into mechanical factors, biological (local and systemic) factors, and infection. Infection is present in ~40% of fracture non-unions, often after open fractures or impaired wound healing, but in 5% of all non-unions infection is present without any clinical or serological suspicion. Methods to improve the sensitivity of investigation in the search of infection include the use of; sonication of implants, direct inoculation of theatre specimens into broth, and histological examination of non-union site tissue. Awareness should be given to the potential anti-osteogenic effect of bisphosphonates (in primary fracture repair) and certain classes of antibiotics. Early cases of delayed/non-union with sufficient mechanical stability and biologically active bone can be managed by stimulation of fracture healing. Late presenting non-union typically requires revision of the fixation construct and stimulation of the callus to induce fracture union.

Evaluation of Staphylococcus aureus eradication therapy in orthopaedic surgery.

PURPOSE: Despite WHO recommendations, there is currently no national screening and eradication policy for the detection of methicillin-sensitive Staphylococcus aureus (MSSA) in the UK prior to elective orthopaedic surgery. This study aimed to evaluate the effectiveness of current standard methicillin-resistant S. aureus (MRSA) eradication therapies in the context of S. aureus (both MRSA and MSSA) decolonization in an elective orthopaedic population. METHODOLOGY: A total of 100 patients awaiting joint replacement surgery who were positive for S. aureus on PCR nasal screening underwent the current standard MRSA pre-operative decolonization regimen for 5 days. Prior to commencement of the eradication therapy, swabs of the anterior nares, throat and perineum were taken for culture. Further culture swabs were taken at 48-96 h following treatment, at hospital admission for surgery and at hospital discharge. Following the completion of treatment, patients were asked to provide feedback on their experience using Likert rating scales. The primary outcome of this study was S. aureus clearance 48-96 h following eradication treatment.Results/Key Findings. Clearance of S. aureus 48-96 h following treatment was 94 % anterior nares, 66 % throat and 88 % groin. Mean completion with nasal mupirocin was 98 %. There was no statistically significant recolonization effect between the end of the eradication treatment period and the day of surgery (P>0.05) at a median time of 10 days. CONCLUSION: Current MRSA decolonisation regimens are well tolerated and effective for MSSA decolonization for the anterior nares and groin. The decolonization effect is preserved for at least 10 days following treatment.

Unexpected synergistic and antagonistic antibiotic activity against Staphylococcus biofilms.

Objectives: To evaluate putative anti-staphylococcal biofilm antibiotic combinations used in the management of periprosthetic joint infections (PJIs). Methods: Using the dissolvable bead biofilm assay, the minimum biofilm eradication concentration (MBEC) was determined for the most commonly used antimicrobial agents and combination regimens against staphylococcal PJIs. The established fractional inhibitory concentration (FIC) index was modified to create the fractional biofilm eradication concentration (FBEC) index to evaluate synergism or antagonism between antibiotics. Results: Only gentamicin (MBEC 64 mg/L) and daptomycin (MBEC 64 mg/L) were observed to be effective antistaphylococcal agents at clinically achievable concentrations. Supplementation of gentamicin with daptomycin, vancomycin or ciprofloxacin resulted in a similar or lower MBEC than gentamicin alone (FBEC index 0.25-2). Conversely, when rifampicin, clindamycin or linezolid was added to gentamicin, there was an increase in the MBEC of gentamicin relative to its use as a monotherapy (FBEC index 8-32). Conclusions: This study found that gentamicin and daptomycin were the only effective single-agent antibiotics against established Staphylococcus biofilms. Interestingly the addition of a bacteriostatic antibiotic was found to antagonize the ability of gentamicin to eradicate Staphylococcus biofilms.

Underestimation of Staphylococcus aureus (MRSA and MSSA) carriage associated with standard culturing techniques: One third of carriers missed.

OBJECTIVES: Nasal carriers of Staphylococcus (S.) aureus (MRSA and MSSA) have an increased risk for healthcare-associated infections. There are currently limited national screening policies for the detection of S. aureus despite the World Health Organization's recommendations. This study aimed to evaluate the diagnostic performance of molecular and culture techniques in S. aureus screening, determine the cause of any discrepancy between the diagnostic techniques, and model the potential effect of different diagnostic techniques on S. aureus detection in orthopaedic patients. METHODS: Paired nasal swabs for polymerase chain reaction (PCR) assay and culture of S. aureus were collected from a study population of 273 orthopaedic outpatients due to undergo joint arthroplasty surgery. RESULTS: The prevalence of MSSA nasal colonization was found to be between 22.4% to 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 approximately one-third of patients undergoing joint arthroplasty surgery. CONCLUSION: Modelling these results to national surveillance data, it was estimated that approximately 5000 to 8000 S. aureus surgical site infections could be prevented, and approximately $140 million to $950 million (approximately £110 million to £760 million) saved in treatment costs annually in the United States and United Kingdom combined, by using alternative diagnostic methods to direct culture in preoperative S. aureus screening and eradication programmes.Cite this article: S. T. J. Tsang, M. P. McHugh, D. Guerendiain, P. J. Gwynne, J. Boyd, A. H. R. W. Simpson, T. S. Walsh, I. F. Laurenson, K. E. Templeton. Underestimation of Staphylococcus aureus (MRSA and MSSA) carriage associated with standard culturing techniques: One third of carriers missed. Bone Joint Res 2018;7:79-84. DOI: 10.1302/2046-3758.71.BJR-2017-0175.R1.

Outcomes following debridement, antibiotics and implant retention in the management of periprosthetic infections of the hip: a review of cohort studies.

AIMS: The aims of the study were to review and analyse the reported series of debridement, antibiotics and implant retention (DAIR) in the management of infected total hip arthroplasties (THAs) to establish the overall success and the influencing factors. PATIENTS AND METHODS: Using a standardised recognised study protocol, meta-analysis of observational studies in epidemiology guidelines, a comprehensive review and analysis of the literature was performed. The primary outcome measure was the success of treatment. The search strategy and inclusion criteria which involved an assessment of quality yielded 39 articles for analysis, which included 1296 patients. RESULTS: The proportion of success following DAIR in the management of an infected THA appeared to improve after 2004 with a pooled mean proportion of success of 72.2%. For all reported series, from 1977 onwards, there was improved success with early debridement (< 7 days; 75.7%) and exchange of modular components (77.5%). There was a statistically non-significant improvement if debridement was performed within four weeks of the initial procedure (73.0%). CONCLUSION: The reported success following DAIR has improved since 2004. The only determinants of outcome which we found were the timing of debridement after the onset of symptoms of infection and the exchange of modular components. Cite this article: Bone Joint J 2017;99-B:1488-66.

The dissolvable bead: A novel in vitro biofilm model for evaluating antimicrobial resistance.

In vitro biofilm assays are a vital first step in the assessment of therapeutic effectiveness. Current biofilm models have been found to be limited by throughput, reproducibility, and cost. We present a novel in vitro biofilm model, utilising a sodium alginate substratum for surface biofilm colony formation, which can be readily dissolved for accurate evaluation of viable organisms. The dissolving bead biofilm assay was evaluated using a range of clinically relevant strains. The reproducibility and responsiveness of the assay to an antimicrobial challenge was assessed using standardised methods. Cryo-scanning electron microscopy was used to image biofilm colonies. Biofilms were grown for 20h prior to testing. The model provides a reproducible and responsive assay to clinically-relevant antimicrobial challenges, as defined by established guidelines. Moreover cryo-scanning electron microscopy demonstrates that biofilm formation is localised exclusively to the alginate bead surface. Our results suggest that this simple model provides a robust and adaptable assay for the investigation of bacterial biofilms.

A cohort study of tibialis anterior tendon shortening in combination with calf muscle lengthening in spastic equinus in cerebral palsy.

The aim of this study was to evaluate the outcome of combined tibialis anterior tendon shortening (TATS) and calf muscle-tendon lengthening (CMTL) in spastic equinus. Prospectively collected data was analysed in 26 patients with hemiplegic (n=13) and diplegic (n=13) cerebral palsy (CP) (GMFCS level I or II, 14 males, 12 females, age range 10-35 years; mean 16.8 years). All patients had pre-operative 3D gait analysis and a further analysis at a mean of 17.1 months (±5.6months) after surgery. None was lost to follow-up. Twenty-eight combined TATS and CMTL were undertaken and 19 patients had additional synchronous multilevel surgery. At follow-up 79% of patients had improved foot positioning at initial contact, whilst 68% reported improved fitting or reduced requirement of orthotic support. Statistically significant improvements were seen in the Movement Analysis Profile for ankle dorsi-/plantarflexion (4.15°, p=0.032), maximum ankle dorsiflexion during swing phase (11.68°, p<0.001), and Edinburgh Visual Gait Score (EVGS) (4.85, p=0.014). Diplegic patients had a greater improvement in the EVGS than hemiplegics (6.27 -vs- 2.21, p=0.024). The originators of combined TATS and CMTL showed that it improved foot positioning during gait. The present study has independently confirmed favourable outcomes in a similar patient population and added additional outcome measures, the EVGS, foot positioning at initial contact, and maximum ankle dorsiflexion during swing phase. Study limitations include short term follow-up in a heterogeneous population and that 19 patients had additional surgery. TATS combined with CMTL is a recommended option for spastic equinus in ambulatory patients with CP.

Exchange nailing for nonunion of diaphyseal fractures of the tibia: our results and an analysis of the risk factors for failure.

AIMS: The aim of this study was to identify risk factors for the failure of exchange nailing in nonunion of tibial diaphyseal fractures. PATIENTS AND METHODS: A cohort of 102 tibial diaphyseal nonunions in 101 patients with a mean age of 36.9 years (15 to 74) were treated between January 1992 and December 2012 by exchange nailing. Of which 33 (32%) were initially open injuries. The median time from primary fixation to exchange nailing was 6.5 months (interquartile range (IQR) 4.3 to 9.8 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. RESULTS: Multiple causes for the primary nonunion were found for 28 (27%) tibiae, with infection present in 32 (31%). Six patients were lost to follow-up. Further surgical procedures were required in 35 (36%) nonunions. Other fixation modalities were required in five fractures. A single nail exchange procedure achieved union in 60/96 (63%) of all nonunions. Only 11 out of 31 infected nonunions (35.4%) healed after one exchange nail procedure. Up to five repeated exchange nailings, with or without bone grafting, ultimately achieved union in 89 (93%) fractures. The median time to union after exchange nailing was 8.7 months (IQR 5.7 to 14.0 months). Univariate analysis confirmed that an oligotrophic/atrophic pattern of nonunion (p = 0.002), a bone gap of 5 mm or more (p = 0.04) and infection (p < 0.001), were predictive for failure of exchange nailing Multiple regression analysis found that infection was the strongest predictor of failure (p < 0.001). CONCLUSION: Exchange nailing is an effective treatment for aseptic tibial diaphyseal nonunion. However, in the presence of severe infection with a highly resistant organism, or extensive sclerosis of the bone, other fixation modalities, such as Ilizarov treatment, should be considered. TAKE HOME MESSAGE: Exchange nailing is an effective treatment for aseptic tibial diaphyseal nonunion.

Exchange nailing for femoral diaphyseal fracture non-unions: Risk factors for failure.

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, of which six were open injuries. The median time to exchange nailing from primary fixation was 8.4 months. The main outcome measures were union, number of secondary fixation procedures required to achieve union and time to union. Multiple causes for non-union were found in 16 (40%) cases, with infection present in 12 (30.0%) patients. Further surgical procedures were required in nine (22.5%) cases, one of whom (2.5%) required the use of another fixation modality to achieve union. Union was ultimately achieved with exchange nailing in 34/37 (91.9%) patients. The median time to union after the exchange nailing was 9.4 months. Cigarette smoking and infection were risk factors for failure of exchange nailing. Multivariate analysis found infection to be the strongest predictor of exchange failure (p<0.05). Exchange nailing is an effective treatment for aseptic femoral diaphyseal fracture non-union. However, 50% of patients undergoing exchange nailing in the presence of infection required at least one further procedure. It is important to counsel patients of this so that they can plan for it and do not consider that the first exchange operation has failed.

When does hip fracture surgery fail?

INTRODUCTION: Hip fractures remain the most common orthopaedic injury requiring hospital admission. Failed surgery for any cause carries a higher morbidity, mortality, and healthcare-related cost. The aims of this study were to determine risk factors for surgical complications of hip fracture surgery, when they occurred and their effect on mortality. PATIENTS AND METHODS: From a prospectively collected consecutive database of 795 hip fractures admitted between July 2007 and June 2008, all surgical and non-surgical complications were identified as well as re-operation for any cause and mortality in the 4 years since surgery. RESULTS: Fifty-five (6.9%) patients were found to have developed a surgical complication requiring further intervention. Risk factors included younger age, smoking and cannulated screw fixation. Cannulated screw fixation was associated with a 30.9% rate of re-operation. Post-operative medical complication occurred in 21.8%. It was associated with a 78.5% mortality at 4 years with a median time to mortality of 58 days (95% CI 0-120 days). CONCLUSIONS: Mechanical failure was the most common reason for cannulated screw re-operation. Hip hemiarthroplasty most commonly failed by infection. Inter-trochanteric and sub-trochanteric fracture fixation had very low failure rates. Post-operative medical complications, but not surgical complications, were associated with a higher mortality rate.

Adverse peri-operative outcomes following elective total hip replacement in diabetes mellitus: a systematic review and meta-analysis of cohort studies.

Total hip replacement (THR) has been shown to be a cost-effective procedure. However, it is not risk-free. Certain conditions, such as diabetes mellitus, are thought to increase the risk of complications. In this study we have evaluated the prevalence of diabetes mellitus in patients undergoing THR and the associated risk of adverse operative outcomes. A meta-analysis and systematic review were conducted according to the guidelines of the meta-analysis of observational studies in epidemiology. Inclusion criteria were observational studies reporting the prevalence of diabetes in the study population, accompanied by reports of at least one of the following outcomes: venous thromboembolic events; acute coronary events; infections of the urinary tract, lower respiratory tract or surgical site; or requirement for revision arthroplasty. Altman and Bland's methods were used to calculate differences in relative risks. The prevalence of diabetes mellitus was found to be 5.0% among patients undergoing THR, and was associated with an increased risk of established surgical site infection (odds ratio (OR) 2.04 (95% confidence interval (CI) 1.52 to 2.76)), urinary infection (OR 1.43 (95% CI 1.33 to 1.55)) and lower respiratory tract infections (OR 1.95 (95% CI 1.61 to 2.26)). Diabetes mellitus is a relatively common comorbidity encountered in THR. Diabetic patients have a higher rate of developing both surgical site and non-surgical site infections following THR.

Detection and characterisation of beta-globin gene cluster deletions in Chinese using multiplex ligation-dependent probe amplification.

BACKGROUND: Deletions in the beta-globin cluster causing thalassaemia and hereditary persistence of fetal haemoglobin (HPFH) are uncommon and difficult to detect. Data in Chinese are very scarce. AIMS: To use a recently available technique to investigate the frequencies and nature of beta-globin cluster deletions in Chinese. METHODS: 106 subjects with phenotypes of thalassaemia or HPFH and suspected to have deletions in the beta-globin cluster were studied. A commercially available kit employing multiplex ligation-dependent probe amplification (MLPA) was used to screen for deletions. Gap PCR and direct nucleotide sequencing were used to characterise deletions detected. RESULTS: 17 deletions in the beta-globin cluster were found in 17 patients: 8 of Chinese ((A)gammadeltabeta)(0) thalassaemia, 7 of Southeast Asian (Vietnamese) deletion and 2 of Thai ((A)gammadeltabeta)(0) thalassaemia. The only type of deletion detected in deltabeta-thalassaemia was Chinese ((A)gammadeltabeta)(0) thalassaemia. The deletional form of HPFH was rarely seen in only 1 case of Thai ((A)gammadeltabeta)(0) thalassaemia. Deletions presenting as beta-thalassaemia trait and raised HbF were all of the Southeast Asian (Vietnamese) deletion type. When these deletions were co-inherited with classical beta-thalassaemia mutations in compound heterozygous states, the phenotypes could be very variable. CONCLUSIONS: In the Chinese population, there are only relatively few types of deletions seen in the beta-globin cluster. MLPA is a fast and effective way of screening for these deletions. Characterisation of these deletions allows the development of simpler and more specific PCR-based tests for routine diagnostic use. Accurate prediction of phenotype is not always feasible. The molecular defects in many cases of HPFH still await discovery.

The HBS1L-MYB intergenic region on chromosome 6q23 is a quantitative trait locus controlling fetal haemoglobin level in carriers of beta-thalassaemia.

BACKGROUND: Fetal haemoglobin (HbF) level modifies the clinical severity of HBB disorders. Intergenic variants of HBS1L-MYB on chromosome 6q23 have recently been shown to be a major quantitative trait locus (QTL) influencing HbF levels in normal Caucasian adults. METHODS: A unique and well-characterised cohort of 238 Chinese subjects with beta-thalassaemia trait was used to conduct a single-nucleotide polymorphism (SNP) association study for HbF level. RESULTS: Within this locus, 29 trait-associated SNPs in a non-coding 56 kb segment were identified. They were divided into five linkage disequilibrium (LD) blocks in the Chinese participants. CONCLUSIONS: The data independently validate for the first time the significance of the HBS1L-MYB intergenic region in regulating HbF expression in a separate ethnic group that has a high prevalence of beta-thalassaemia. Functional studies to unravel the biological significance of this region in regulating HbF production is clearly indicated, which may lead to new strategies to modify the disease course of severe HBB disorders.