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Bone & Joint Research
Vol. 4, Issue 9 | Pages 154 - 162
1 Sep 2015

Objective. Clinical studies of patients with bone sarcomas have been challenged by insufficient numbers at individual centres to draw valid conclusions. Our objective was to assess the feasibility of conducting a definitive multi-centre randomised controlled trial (RCT) to determine whether a five-day regimen of post-operative antibiotics, in comparison to a 24-hour regimen, decreases surgical site infections in patients undergoing endoprosthetic reconstruction for lower extremity primary bone tumours. . Methods. We performed a pilot international multi-centre RCT. We used central randomisation to conceal treatment allocation and sham antibiotics to blind participants, surgeons, and data collectors. We determined feasibility by measuring patient enrolment, completeness of follow-up, and protocol deviations for the antibiotic regimens. . Results. We screened 96 patients and enrolled 60 participants (44 men and 16 women) across 21 sites from four countries over 24 months (mean 2.13 participants per site per year, standard deviation 2.14). One participant was lost to follow-up and one withdrew consent. Complete data were obtained for 98% of eligible patients at two weeks, 83% at six months, and 73% at one year (the remainder with partial data or pending queries). In total, 18 participants missed at least one dose of antibiotics or placebo post-operatively, but 93% of all post-operative doses were administered per protocol. . Conclusions. It is feasible to conduct a definitive multi-centre RCT of post-operative antibiotic regimens in patients with bone sarcomas, but further expansion of our collaborative network will be critical. We have demonstrated an ability to coordinate in multiple countries, enrol participants, maintain protocol adherence, and minimise losses to follow-up. Cite this article: Bone Joint Res;4:154–162


The Bone & Joint Journal
Vol. 106-B, Issue 12 | Pages 1377 - 1384
1 Dec 2024
Fontalis A Yasen AT Giebaly DE Luo TD Magan A Haddad FS

Periprosthetic joint infection (PJI) represents a complex challenge in orthopaedic surgery associated with substantial morbidity and healthcare expenditures. The debridement, antibiotics, and implant retention (DAIR) protocol is a viable treatment, offering several advantages over exchange arthroplasty. With the evolution of treatment strategies, considerable efforts have been directed towards enhancing the efficacy of DAIR, including the development of a phased debridement protocol for acute PJI management. This article provides an in-depth analysis of DAIR, presenting the outcomes of single-stage, two-stage, and repeated DAIR procedures. It delves into the challenges faced, including patient heterogeneity, pathogen identification, variability in surgical techniques, and antibiotics selection. Moreover, critical factors that influence the decision-making process between single- and two-stage DAIR protocols are addressed, including team composition, timing of the intervention, antibiotic regimens, and both anatomical and implant-related considerations. By providing a comprehensive overview of DAIR protocols and their clinical implications, this annotation aims to elucidate the advancements, challenges, and potential future directions in the application of DAIR for PJI management. It is intended to equip clinicians with the insights required to effectively navigate the complexities of implementing DAIR strategies, thereby facilitating informed decision-making for optimizing patient outcomes. Cite this article: Bone Joint J 2024;106-B(12):1377–1384


Bone & Joint Open
Vol. 4, Issue 10 | Pages 742 - 749
6 Oct 2023
Mabrouk A Abouharb A Stewart G Palan J Pandit H

Aims. Prophylactic antibiotic regimens for elective primary total hip and knee arthroplasty vary widely across hospitals and trusts in the UK. This study aimed to identify antibiotic prophylaxis regimens currently in use for elective primary arthroplasty across the UK, establish variations in antibiotic prophylaxis regimens and their impact on the risk of periprosthetic joint infection (PJI) in the first-year post-index procedure, and evaluate adherence to current international consensus guidance. Methods. The guidelines for the primary and alternative recommended prophylactic antibiotic regimens in clean orthopaedic surgery (primary arthroplasty) for 109 hospitals and trusts across the UK were sought by searching each trust and hospital’s website (intranet webpages), and by using the MicroGuide app. The mean cost of each antibiotic regimen was calculated using price data from the British National Formulary (BNF). Regimens were then compared to the 2018 Philadelphia Consensus Guidance, to evaluate adherence to international guidance. Results. The primary choice and dosing of the prophylactic antimicrobial regimens varied widely. The two most used regimens were combined teicoplanin and gentamicin, and cefuroxime followed by two or three doses of cefuroxime eight-hourly, recommended by 24 centres (22.02%) each. The alternative choice and dosing of the prophylactic antimicrobial regimen also varied widely across the 83 centres with data available. Prophylaxis regimens across some centres fail to cover the likeliest causes of surgical site infection (SSI). Five centres (4.59%) recommend co-amoxiclav, which confers no Staphylococcus coverage, while 33 centres (30.28%) recommend cefuroxime, which confers no Enterococcus coverage. Limited adherence to 2018 Philadelphia Consensus Guidance was observed, with 67 centres (61.50%) not including a cephalosporin in their guidance. Conclusion. This analysis of guidance on antimicrobial prophylaxis in primary arthroplasty across 109 hospitals and trusts in the UK has identified widespread variation in primary and alternative antimicrobial regimens currently recommended. Cite this article: Bone Jt Open 2023;4(10):742–749


The Bone & Joint Journal
Vol. 101-B, Issue 6_Supple_B | Pages 9 - 15
1 Jun 2019
Wyles CC Hevesi M Osmon DR Park MA Habermann EB Lewallen DG Berry DJ Sierra RJ

Aims. The aims of this study were to characterize antibiotic choices for perioperative total knee arthroplasty (TKA) and total hip arthroplasty (THA) prophylaxis, assess antibiotic allergy testing efficacy, and determine rates of prosthetic joint infection (PJI) based on perioperative antibiotic regimen. Patients and Methods. We evaluated all patients undergoing primary TKA or THA at a single academic institution between January 2004 and May 2017, yielding 29 695 arthroplasties (22 705 patients), with 3411 arthroplasties in 2576 patients (11.5%) having undergone preoperative allergy testing. A series of institutional databases were combined to identify allergy consultation outcomes, perioperative antibiotic regimen, and infection-free survivorship until final follow-up. Results. Among 2576 allergy-tested patients, 2493 patients (97%) were cleared to use cephalosporins. For the entire cohort, 28 174 arthroplasties (94.9%) received cefazolin and 1521 (5.1%) received non-cefazolin antibiotics. Infection-free survivorship was significantly higher among arthroplasties receiving cefazolin compared with non-cefazolin antibiotics, with 0.06% higher survival free of infection at one month, 0.56% at two months, 0.61% at one year, and 1.19% at ten years (p < 0.001). Overall, the risk of PJI was 32% lower in patients treated with cefazolin after adjusting for the American Society of Anesthesiologists (ASA) classification, joint arthroplasty (TKA or THA), and body mass index (BMI; p < 0.001). The number needed to treat with cefazolin to prevent one PJI was 164 patients at one year and 84 patients at ten years. Therefore, potentially 6098 PJIs could be prevented by one year and 11 905 by ten years in a cohort of 1 000 000 primary TKA and THA patients. Conclusion. PJI rates are significantly higher when non-cefazolin antibiotics are used for perioperative TKA and THA prophylaxis, highlighting the positive impact of preoperative antibiotic allergy testing to increase cefazolin usage. Given the low rate of true penicillin allergy positivity, and the readily modifiable risk factor that antibiotic choice provides, we recommend perioperative testing and clearance for all patients presenting with penicillin and cephalosporin allergies. Cite this article: Bone Joint J 2019;101-B(6 Supple B):9–15


Bone & Joint Research
Vol. 9, Issue 2 | Pages 49 - 59
1 Feb 2020
Yu K Song L Kang HP Kwon H Back J Lee FY

Aims. To characterize the intracellular penetration of osteoblasts and osteoclasts by methicillin-resistant Staphylococcus aureus (MRSA) and the antibiotic and detergent susceptibility of MRSA in bone. Methods. Time-lapse confocal microscopy was used to analyze the interaction of MRSA strain USA300 with primary murine osteoblasts and osteoclasts. The effects of early and delayed antibiotic treatments on intracellular and extracellular bacterial colony formation and cell death were quantified. We tested the effects of cefazolin, gentamicin, vancomycin, tetracycline, rifampicin, and ampicillin, as well as agents used in surgical preparation and irrigation. Results. MRSA infiltrated bone-resident cells within 15 to 30 minutes. Penetration was most effectively prevented with early (i.e. 30 minutes) antibiotic administration. The combined administration of rifampicin with other antibiotics potentiated their protective effects against MRSA-induced cytotoxicity and most significantly reduced extracellular bacterial bioburden. Gentamicin-containing compounds were most effective in reducing intracellular MRSA bioburden. Of the surgical preparation agents evaluated, betadine reduced in vitro MRSA growth to the greatest extent. Conclusion. The standard of care for open fractures involves debridement and antibiotics within the first six hours of injury but does not account for the window in which bacteria penetrate cells. Antibiotics must be administered as early as possible after injury or prior to incision to prevent intracellular infestation. Rifampicin can potentiate the capacity of antibiotic regimens to reduce MRSA-induced cytotoxicity. Cite this article:Bone Joint Res. 2020;9(2):49–59


The Bone & Joint Journal
Vol. 103-B, Issue 6 | Pages 1070 - 1077
1 Jun 2021
Hipfl C Mooij W Perka C Hardt S Wassilew GI

Aims. The purpose of this study was to evaluate unexpected positive cultures in total hip arthroplasty (THA) revisions for presumed aseptic loosening, to assess the prevalence of low-grade infection using two definition criteria, and to analyze its impact on implant survival after revision. Methods. A total of 274 THA revisions performed for presumed aseptic loosening from 2012 to 2016 were reviewed. In addition to obtaining intraoperative tissue cultures from all patients, synovial and sonication fluid samples of the removed implant were obtained in 215 cases (79%) and 101 cases (37%), respectively. Histopathological analysis was performed in 250 cases (91%). Patients were classified as having low-grade infections according to institutional criteria and Musculoskeletal Infection Society (MSIS) International Consensus Meeting (ICM) 2013 criteria. Low-grade infections according to institutional criteria were treated with targeted antibiotics for six weeks postoperatively. Implant failure was defined as the need for re-revision resulting from periprosthetic joint infection (PJI) and aseptic reasons. The mean follow-up was 68 months (26 to 95). Results. Unexpected positive intraoperative samples were found in 77 revisions (28%). Low-grade infection was diagnosed in 36 cases (13%) using institutional criteria and in nine cases (3%) using MSIS ICM 2013 criteria. In all, 41 patients (15%) had single specimen growth of a low-virulent pathogen and were deemed contaminated. Coagulase-negative Staphylococcus and anaerobes were the most commonly isolated bacteria. Implant failure for PJI was higher in revisions with presumed contaminants (5/41, 12%) compared to those with low-grade infections (2/36, 6%) and those with negative samples (5/197, 3%) (p = 0.021). The rate of all-cause re-revision was similar in patients diagnosed with low-grade infections (5/36, 14%) and those with presumed contaminants (6/41, 15%) and negative samples (21/197, 11%) (p = 0.699). Conclusion. Our findings suggest that the presumption of culture contamination in aseptic revision hip arthroplasty may increase the detection of PJI. In this cohort, the presence of low-grade infection did not increase the risk of re-revision. Further studies are needed to assess the relevance of single specimen growth and the benefits of specific postoperative antibiotic regimens. Cite this article: Bone Joint J 2021;103-B(6):1070–1077


The Bone & Joint Journal
Vol. 105-B, Issue 8 | Pages 850 - 856
1 Aug 2023
Azamgarhi T Warren S Fouch S Standing JF Gerrand C

The recently published Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY) trial found no benefit in extending antibiotic prophylaxis from 24 hours to five days after endoprosthetic reconstruction for lower limb bone tumours. PARITY is the first randomized controlled trial in orthopaedic oncology and is a huge step forward in understanding antibiotic prophylaxis. However, significant gaps remain, including questions around antibiotic choice, particularly in the UK, where cephalosporins are avoided due to concerns of Clostridioides difficile infection. We present a review of the evidence for antibiotic choice, dosing, and timing, and a brief description of PARITY, its implication for practice, and the remaining gaps in our understanding.

Cite this article: Bone Joint J 2023;105-B(8):850–856.


Bone & Joint Research
Vol. 13, Issue 8 | Pages 401 - 410
15 Aug 2024
Hu H Ding H Lyu J Chen Y Huang C Zhang C Li W Fang X Zhang W

Aims

This aim of this study was to analyze the detection rate of rare pathogens in bone and joint infections (BJIs) using metagenomic next-generation sequencing (mNGS), and the impact of mNGS on clinical diagnosis and treatment.

Methods

A retrospective analysis was conducted on 235 patients with BJIs who were treated at our hospital between January 2015 and December 2021. Patients were divided into the no-mNGS group (microbial culture only) and the mNGS group (mNGS testing and microbial culture) based on whether mNGS testing was used or not.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 535 - 545
2 Oct 2024
Zou C Guo W Mu W Wahafu T Li Y Hua L Xu B Cao L

Aims

We aimed to determine the concentrations of synovial vancomycin and meropenem in patients treated by single-stage revision combined with intra-articular infusion following periprosthetic joint infection (PJI), thereby validating this drug delivery approach.

Methods

We included 14 patients with PJI as noted in their medical records between November 2021 and August 2022, comprising eight hip and seven knee joint infections, with one patient experiencing bilateral knee infections. The patients underwent single-stage revision surgery, followed by intra-articular infusion of vancomycin and meropenem (50,000 µg/ml). Synovial fluid samples were collected to assess antibiotic concentrations using high-performance liquid chromatography.


Bone & Joint Open
Vol. 5, Issue 5 | Pages 435 - 443
23 May 2024
Tadross D McGrory C Greig J Townsend R Chiverton N Highland A Breakwell L Cole AA

Aims

Gram-negative infections are associated with comorbid patients, but outcomes are less well understood. This study reviewed diagnosis, management, and treatment for a cohort treated in a tertiary spinal centre.

Methods

A retrospective review was performed of all gram-negative spinal infections (n = 32; median age 71 years; interquartile range 60 to 78), excluding surgical site infections, at a single centre between 2015 to 2020 with two- to six-year follow-up. Information regarding organism identification, antibiotic regime, and treatment outcomes (including clinical, radiological, and biochemical) were collected from clinical notes.


The Bone & Joint Journal
Vol. 95-B, Issue 6 | Pages 831 - 837
1 Jun 2013
Dunkel N Pittet D Tovmirzaeva L Suvà D Bernard L Lew D Hoffmeyer P Uçkay I

We undertook a retrospective case-control study to assess the clinical variables associated with infections in open fractures. A total of 1492 open fractures were retrieved; these were Gustilo and Anderson grade I in 663 (44.4%), grade II in 370 (24.8%), grade III in 310 (20.8%) and unclassifiable in 149 (10.0%). The median duration of prophylaxis was three days (interquartile range (IQR) 1 to 3), and the median number of surgical interventions was two (1 to 9). We identified 54 infections (3.6%) occurring at a median of ten days (IQR 5 to 20) after trauma. Pathogens intrinsically resistant to the empirical antibiotic regimen used (enterococci, Enterobacter spp, Pseudomonas spp) were documented in 35 of 49 cases (71%). In multivariable regression analyses, grade III fractures and vascular injury or compartment syndrome were significantly associated with infection. Overall, compared with one day of antibiotic treatment, two to three days (odds ratio (OR) 0.6 (95% confidence interval (CI) 0.2 to 2.0)), four to five days (OR 1.2 (95% CI 0.3 to 4.9)), or > five days (OR 1.4 (95% CI 0.4 to 4.4)) did not show any significant differences in the infection risk. These results were similar when multivariable analysis was performed for grade III fractures only (OR 0.3 (95% CI 0.1 to 3.4); OR 0.6 (95% CI 0.2 to 2.1); and OR 1.7 (95% CI 0.5 to 6.2), respectively). Infection in open fractures is related to the extent of tissue damage but not to the duration of prophylactic antibiotic therapy. Even for grade III fractures, a one-day course of prophylactic antibiotics might be as effective as prolonged prophylaxis. Cite this article: Bone Joint J 2013;95-B:831–7


Bone & Joint 360
Vol. 12, Issue 4 | Pages 26 - 29
1 Aug 2023

The August 2023 Shoulder & Elbow Roundup360 looks at: Motor control or strengthening exercises for rotator cuff-related shoulder pain? A multi-arm randomized controlled trial; Does the choice of antibiotic prophylaxis influence reoperation rate in primary shoulder arthroplasty?; Common shoulder injuries in sport: grading the evidence; The use of medial support screw was associated with axillary nerve injury after plate fixation of proximal humeral fracture using a minimally invasive deltoid-splitting approach; MRI predicts outcomes of conservative treatment in patients with lateral epicondylitis; Association between surgeon volume and patient outcomes after elective shoulder arthroplasty; Arthroscopic decompression of calcific tendinitis without cuff repair; Functional outcome after nonoperative management of minimally displaced greater tuberosity fractures and predictors of poorer patient experience.


The Bone & Joint Journal
Vol. 106-B, Issue 7 | Pages 720 - 727
1 Jul 2024
Wu H Wang X Shen J Wei Z Wang S Xu T Luo F Xie Z

Aims

This study aimed to investigate the clinical characteristics and outcomes associated with culture-negative limb osteomyelitis patients.

Methods

A total of 1,047 limb osteomyelitis patients aged 18 years or older who underwent debridement and intraoperative culture at our clinic centre from 1 January 2011 to 31 December 2020 were included. Patient characteristics, infection eradication, and complications were analyzed between culture-negative and culture-positive cohorts.


Bone & Joint 360
Vol. 13, Issue 3 | Pages 37 - 40
3 Jun 2024

The June 2024 Trauma Roundup360 looks at: Skin antisepsis before surgical fixation of limb fractures; Comparative analysis of intramedullary nail versus plate fixation for fibula fracture in supination external rotation type IV ankle injury; Early weightbearing versus late weightbearing after intramedullary nailing for distal femoral fracture (AO/OTA 33) in elderly patients: a multicentre propensity-matched study; Long-term outcomes with spinal versus general anaesthesia for hip fracture surgery; Operative versus nonoperative management of unstable medial malleolus fractures: a randomized clinical trial; Impact of smoking status on fracture-related infection characteristics and outcomes; Reassessing empirical antimicrobial choices in fracture-related infections; Development and validation of the Nottingham Trauma Frailty Index (NTFI) for older trauma patients.


Bone & Joint 360
Vol. 12, Issue 6 | Pages 42 - 45
1 Dec 2023

The December 2023 Children’s orthopaedics Roundup360 looks at: A comprehensive nonoperative treatment protocol for developmental dysplasia of the hip in infants; How common are refractures in childhood?; Femoral nailing for paediatric femoral shaft fracture in children aged eight to ten years; Who benefits from allowing the physis to grow in slipped capital femoral epiphysis?; Paediatric patients with an extremity bone tumour: a secondary analysis of the PARITY trial data; Split tibial tendon transfers in cerebral palsy equinovarus foot deformities; Liposomal bupivacaine nerve block: an answer to opioid use?; Correction with distal femoral transphyseal screws in hemiepiphysiodesis for coronal-plane knee deformity.


Bone & Joint Open
Vol. 4, Issue 11 | Pages 832 - 838
3 Nov 2023
Pichler L Li Z Khakzad T Perka C Pumberger M Schömig F

Aims

Implant-related postoperative spondylodiscitis (IPOS) is a severe complication in spine surgery and is associated with high morbidity and mortality. With growing knowledge in the field of periprosthetic joint infection (PJI), equivalent investigations towards the management of implant-related infections of the spine are indispensable. To our knowledge, this study provides the largest description of cases of IPOS to date.

Methods

Patients treated for IPOS from January 2006 to December 2020 were included. Patient demographics, parameters upon admission and discharge, radiological imaging, and microbiological results were retrieved from medical records. CT and MRI were analyzed for epidural, paravertebral, and intervertebral abscess formation, vertebral destruction, and endplate involvement. Pathogens were identified by CT-guided or intraoperative biopsy, intraoperative tissue sampling, or implant sonication.


Bone & Joint Research
Vol. 13, Issue 3 | Pages 127 - 135
22 Mar 2024
Puetzler J Vallejo Diaz A Gosheger G Schulze M Arens D Zeiter S Siverino C Richards RG Moriarty TF

Aims

Fracture-related infection (FRI) is commonly classified based on the time of onset of symptoms. Early infections (< two weeks) are treated with debridement, antibiotics, and implant retention (DAIR). For late infections (> ten weeks), guidelines recommend implant removal due to tolerant biofilms. For delayed infections (two to ten weeks), recommendations are unclear. In this study we compared infection clearance and bone healing in early and delayed FRI treated with DAIR in a rabbit model.

Methods

Staphylococcus aureus was inoculated into a humeral osteotomy in 17 rabbits after plate osteosynthesis. Infection developed for one week (early group, n = 6) or four weeks (delayed group, n = 6) before DAIR (systemic antibiotics: two weeks, nafcillin + rifampin; four weeks, levofloxacin + rifampin). A control group (n = 5) received revision surgery after four weeks without antibiotics. Bacteriology of humerus, soft-tissue, and implants was performed seven weeks after revision surgery. Bone healing was assessed using a modified radiological union scale in tibial fractures (mRUST).


Bone & Joint Research
Vol. 12, Issue 6 | Pages 362 - 371
1 Jun 2023
Xu D Ding C Cheng T Yang C Zhang X

Aims

The present study aimed to investigate whether patients with inflammatory bowel disease (IBD) undergoing joint arthroplasty have a higher incidence of adverse outcomes than those without IBD.

Methods

A comprehensive literature search was conducted to identify eligible studies reporting postoperative outcomes in IBD patients undergoing joint arthroplasty. The primary outcomes included postoperative complications, while the secondary outcomes included unplanned readmission, length of stay (LOS), joint reoperation/implant revision, and cost of care. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects model when heterogeneity was substantial.


The Bone & Joint Journal
Vol. 104-B, Issue 10 | Pages 1168 - 1173
1 Oct 2022
Gazendam AM Schneider P Vélez R Ghert M

Aims

The aim of this study was to determine the prevalence and impact of tourniquet use in patients undergoing limb salvage surgery with endoprosthetic reconstruction for a tumour around the knee.

Methods

We retrieved data from the Prophylactic Antibiotic Regimens in Tumor Surgery (PARITY) trial; specifically, differences in baseline characteristics, surgical details, and postoperative functional outcomes between patients who had undergone surgery under tourniquet and those who had not. A linear regression model was created to evaluate the impact of tourniquet use on postoperative Toronto Extremity Salvage Scores (TESSs) while controlling for confounding variables. A negative-binomial regression model was constructed to explore predictors of postoperative length of stay (LOS).


Bone & Joint Research
Vol. 10, Issue 12 | Pages 790 - 796
1 Dec 2021
Fang X Wang Q Yang X Zhang F Huang C Huang Z Shen H Zhang W

Aims

To explore the effect of different durations of antibiotics after stage II reimplantation on the prognosis of two-stage revision for chronic periprosthetic joint infection (PJI).

Methods

This study involved a retrospective collection of patients who underwent two-stage revision for chronic PJI and continued to use extended antibiotic prophylaxis in two regional medical centres from January 2010 to June 2018. The patients were divided into a short (≤ one month) or a long (> one month) course of treatment based on the duration of antibiotics following stage II reimplantation. The difference in the infection control rate between the two groups was compared, and prognostic factors for recurrence were analyzed.


Bone & Joint 360
Vol. 11, Issue 3 | Pages 35 - 37
1 Jun 2022


The Bone & Joint Journal
Vol. 103-B, Issue 6 Supple A | Pages 191 - 195
1 Jun 2021
Gausden EB Shirley MB Abdel MP Sierra RJ

Aims

To describe the risk of periprosthetic joint infection (PJI) and reoperation in patients who have an acute, traumatic wound dehiscence following total knee arthroplasty (TKA).

Methods

From January 2002 to December 2018, 16,134 primary TKAs were performed at a single institution. A total of 26 patients (0.1%) had a traumatic wound dehiscence within the first 30 days. Mean age was 68 years (44 to 87), 38% (n = 10) were female, and mean BMI was 34 kg/m2 (23 to 48). Median time to dehiscence was 13 days (interquartile range (IQR) 4 to 15). The dehiscence resulted from a fall in 22 patients and sudden flexion after staple removal in four. The arthrotomy was also disrupted in 58% (n = 15), including a complete extensor mechanism disruption in four knees. An irrigation and debridement with component retention (IDCR) was performed within 48 hours in 19 of 26 knees and two-thirds were discharged on antibiotic therapy. The mean follow-up was six years (2 to 15). The association of wound dehiscence and the risk of developing a PJI was analyzed.


Bone & Joint 360
Vol. 11, Issue 2 | Pages 41 - 43
1 Apr 2022


Bone & Joint Open
Vol. 3, Issue 4 | Pages 284 - 290
1 Apr 2022
O'Hara NN Carullo J Joshi M Banoub M Claeys KC Sprague S Slobogean GP O'Toole RV

Aims

There is increasing evidence to support the use of topical antibiotics to prevent surgical site infections. Although previous research suggests a minimal nephrotoxic risk with a single dose of vancomycin powder, fracture patients often require multiple procedures and receive additional doses of topical antibiotics. We aimed to determine if cumulative doses of intrawound vancomycin or tobramycin powder for infection prophylaxis increased the risk of drug-induced acute kidney injury (AKI) among fracture patients.

Methods

This cohort study was a secondary analysis of single-centre Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT) trial data. We included patients with a surgically treated appendicular fracture. The primary outcome was drug-induced AKI. The odds of AKI per gram of vancomycin or tobramycin powder were calculated using Bayesian regression models, which adjusted for measured confounders and accounted for the interactive effects of vancomycin and tobramycin.


Bone & Joint Open
Vol. 3, Issue 4 | Pages 314 - 320
7 Apr 2022
Malhotra R Batra S Sugumar PA Gautam D

Aims

Adult patients with history of childhood infection pose a surgical challenge for total hip arthroplasty (THA) due to distorted bony anatomy, soft-tissue contractures, risk of reinfection, and relatively younger age. Therefore, the purpose of the present study was to determine clinical outcome, reinfection rate, and complications in patients with septic sequelae after THA.

Methods

A retrospective analysis was conducted of 91 cementless THAs (57 male and 34 female) performed between 2008 and 2017 in patients who had history of hip infection during childhood. Clinical outcome was measured using Harris Hip Score (HHS) and Modified Merle d’Aubigne and Postel (MAP) score, and quality of life (QOL) using 12-Item Short Form Health Survey Questionnaire (SF-12) components: Physical Component Score (PCS) and Mental Component Score (MCS); limb length discrepancy (LLD) and radiological assessment of the prosthesis was performed at the latest follow-up. Reinfection and revision surgery after THA for any reason was documented.


Bone & Joint Research
Vol. 11, Issue 10 | Pages 700 - 714
4 Oct 2022
Li J Cheung W Chow SK Ip M Leung SYS Wong RMY

Aims

Biofilm-related infection is a major complication that occurs in orthopaedic surgery. Various treatments are available but efficacy to eradicate infections varies significantly. A systematic review was performed to evaluate therapeutic interventions combating biofilm-related infections on in vivo animal models.

Methods

Literature research was performed on PubMed and Embase databases. Keywords used for search criteria were “bone AND biofilm”. Information on the species of the animal model, bacterial strain, evaluation of biofilm and bone infection, complications, key findings on observations, prevention, and treatment of biofilm were extracted.


Bone & Joint Open
Vol. 3, Issue 3 | Pages 252 - 260
17 Mar 2022
Badge H Churches T Xuan W Naylor JM Harris IA

Aims

Antibiotic prophylaxis involving timely administration of appropriately dosed antibiotic is considered effective to reduce the risk of surgical site infection (SSI) after total hip and total knee arthroplasty (THA/TKA). Cephalosporins provide effective prophylaxis, although evidence regarding the optimal timing and dosage of prophylactic antibiotics is inconclusive. The aim of this study is to examine the association between cephalosporin prophylaxis dose, timing, and duration, and the risk of SSI after THA/TKA.

Methods

A prospective multicentre cohort study was undertaken in consenting adults with osteoarthritis undergoing elective primary TKA/THA at one of 19 high-volume Australian public/private hospitals. Data were collected prior to and for one-year post surgery. Logistic regression was undertaken to explore associations between dose, timing, and duration of cephalosporin prophylaxis and SSI. Data were analyzed for 1,838 participants. There were 264 SSI comprising 63 deep SSI (defined as requiring intravenous antibiotics, readmission, or reoperation) and 161 superficial SSI (defined as requiring oral antibiotics) experienced by 249 (13.6%) participants within 365 days of surgery.


Bone & Joint Research
Vol. 11, Issue 2 | Pages 112 - 120
16 Feb 2022
Vittrup SØ Hanberg P Knudsen MB Tøstesen SK Kipp JO Hansen J Jørgensen NP Stilling M Bue M

Aims

Prompt and sufficient broad-spectrum empirical antibiotic treatment is key to preventing infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off (ECOFF) minimal inhibitory concentrations (T > MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC targets were applied: 1 and 4 µg/ml for vancomycin, and 0.125 and 2 µg/ml for meropenem.

Methods

Eight pigs received a single dose of 1,000 mg vancomycin and 1,000 mg meropenem simultaneously over 100 minutes and 10 minutes, respectively. Microdialysis catheters were placed for sampling over eight hours in tibial cancellous bone, cortical bone, and adjacent subcutaneous adipose tissue. Venous blood samples were collected as references.


The Bone & Joint Journal
Vol. 104-B, Issue 7 | Pages 867 - 874
1 Jul 2022
Ji B Li G Zhang X Xu B Wang Y Chen Y Cao L

Aims

Periprosthetic joint infections (PJIs) with prior multiple failed surgery for reinfection represent a huge challenge for surgeons because of poor vascular supply and biofilm formation. This study aims to determine the results of single-stage revision using intra-articular antibiotic infusion in treating this condition.

Methods

A retrospective analysis included 78 PJI patients (29 hips; 49 knees) who had undergone multiple prior surgical interventions. Our cohort was treated with single-stage revision using a supplementary intra-articular antibiotic infusion. Of these 78 patients, 59 had undergone more than two prior failed debridement and implant retentions, 12 patients had a failed arthroplasty resection, three hips had previously undergone failed two-stage revision, and four had a failed one-stage revision before their single-stage revision. Previous failure was defined as infection recurrence requiring surgical intervention. Besides intravenous pathogen-sensitive agents, an intra-articular infusion of vancomycin, imipenem, or voriconazole was performed postoperatively. The antibiotic solution was soaked into the joint for 24 hours for a mean of 16 days (12 to 21), then extracted before next injection. Recurrence of infection and clinical outcomes were evaluated.


Bone & Joint Open
Vol. 3, Issue 1 | Pages 35 - 41
9 Jan 2022
Buchalter DB Nduaguba A Teo GM Kugelman D Aggarwal VK Long WJ

Aims

Despite recent literature questioning their use, vancomycin and clindamycin often substitute cefazolin as the preoperative antibiotic prophylaxis in primary total knee arthroplasty (TKA), especially in the setting of documented allergy to penicillin. Topical povidone-iodine lavage and vancomycin powder (VIP) are adjuncts that may further broaden antimicrobial coverage, and have shown some promise in recent investigations. The purpose of this study, therefore, is to compare the risk of acute periprosthetic joint infection (PJI) in primary TKA patients who received cefazolin and VIP to those who received a non-cephalosporin alternative and VIP.

Methods

This was a retrospective cohort study of 11,550 primary TKAs performed at an orthopaedic hospital between 2013 and 2019. The primary outcome was PJI occurring within 90 days of surgery. Patients were stratified into two groups (cefazolin vs non-cephalosporin) based on their preoperative antibiotic. All patients also received the VIP protocol at wound closure. Bivariate and multiple logistic regression analyses were performed to control for potential confounders and identify the odds ratio of PJI.


The Bone & Joint Journal
Vol. 103-B, Issue 11 | Pages 1702 - 1708
1 Nov 2021
Lawrie CM Kazarian GS Barrack T Nunley RM Barrack RL

Aims

Intra-articular administration of antibiotics during primary total knee arthroplasty (TKA) may represent a safe, cost-effective strategy to reduce the risk of acute periprosthetic joint infection (PJI). Vancomycin with an aminoglycoside provides antimicrobial cover for most organisms isolated from acute PJI after TKA. However, the intra-articular doses required to achieve sustained therapeutic intra-articular levels while remaining below toxic serum levels is unknown. The purpose of this study is to determine the intra-articular and serum levels of vancomycin and tobramycin over the first 24 hours postoperatively after intra-articular administration in primary cementless TKA.

Methods

A prospective cohort study was performed. Patients were excluded if they had poor renal function, known allergic reaction to vancomycin or tobramycin, received intravenous vancomycin, or were scheduled for same-day discharge. All patients received 600 mg tobramycin and 1 g of vancomycin powder suspended in 25 cc of normal saline and injected into the joint after closure of the arthrotomy. Serum from peripheral venous blood and drain fluid samples were collected at one, four, and 24 hours postoperatively. All concentrations are reported in µg per ml.


The Bone & Joint Journal
Vol. 103-B, Issue 2 | Pages 234 - 244
1 Feb 2021
Gibb BP Hadjiargyrou M

Antibiotic resistance represents a threat to human health. It has been suggested that by 2050, antibiotic-resistant infections could cause ten million deaths each year. In orthopaedics, many patients undergoing surgery suffer from complications resulting from implant-associated infection. In these circumstances secondary surgery is usually required and chronic and/or relapsing disease may ensue. The development of effective treatments for antibiotic-resistant infections is needed. Recent evidence shows that bacteriophage (phages; viruses that infect bacteria) therapy may represent a viable and successful solution. In this review, a brief description of bone and joint infection and the nature of bacteriophages is presented, as well as a summary of our current knowledge on the use of bacteriophages in the treatment of bacterial infections. We present contemporary published in vitro and in vivo data as well as data from clinical trials, as they relate to bone and joint infections. We discuss the potential use of bacteriophage therapy in orthopaedic infections. This area of research is beginning to reveal successful results, but mostly in nonorthopaedic fields. We believe that bacteriophage therapy has potential therapeutic value for implant-associated infections in orthopaedics.

Cite this article: Bone Joint J 2021;103-B(2):234–244.


The Bone & Joint Journal
Vol. 102-B, Issue 7 Supple B | Pages 3 - 10
1 Jul 2020
Sosa BR Niu Y Turajane K Staats K Suhardi V Carli A Fischetti V Bostrom M Yang X

Aims

Current treatments of prosthetic joint infection (PJI) are minimally effective against Staphylococcus aureus biofilm. A murine PJI model of debridement, antibiotics, and implant retention (DAIR) was used to test the hypothesis that PlySs2, a bacteriophage-derived lysin, can target S. aureus biofilm and address the unique challenges presented in this periprosthetic environment.

Methods

The ability of PlySs2 and vancomycin to kill biofilm and colony-forming units (CFUs) on orthopaedic implants were compared using in vitro models. An in vivo murine PJI model of DAIR was used to assess the efficacy of a combination of PlySs2 and vancomycin on periprosthetic bacterial load.


The Bone & Joint Journal
Vol. 103-B, Issue 1 | Pages 26 - 31
4 Jan 2021
Kildow BJ Ryan SP Danilkowicz R Lazarides AL Penrose C Bolognesi MP Jiranek W Seyler TM

Aims

Use of molecular sequencing methods in periprosthetic joint infection (PJI) diagnosis and organism identification have gained popularity. Next-generation sequencing (NGS) is a potentially powerful tool that is now commercially available. The purpose of this study was to compare the diagnostic accuracy of NGS, polymerase chain reaction (PCR), conventional culture, the Musculoskeletal Infection Society (MSIS) criteria, and the recently proposed criteria by Parvizi et al in the diagnosis of PJI.

Methods

In this retrospective study, aspirates or tissue samples were collected in 30 revision and 86 primary arthroplasties for routine diagnostic investigation for PJI and sent to the laboratory for NGS and PCR. Concordance along with statistical differences between diagnostic studies were calculated.


Bone & Joint Research
Vol. 10, Issue 1 | Pages 77 - 84
1 Jan 2021
Milstrey A Rosslenbroich S Everding J Raschke MJ Richards RG Moriarty TF Puetzler J

Aims

Biofilm formation is one of the primary reasons for the difficulty in treating implant-related infections (IRIs). Focused high-energy extracorporeal shockwave therapy (fhESWT), which is a treatment modality for fracture nonunions, has been shown to have a direct antibacterial effect on planktonic bacteria. The goal of the present study was to investigate the effect of fhESWT on Staphylococcus aureus biofilms in vitro in the presence and absence of antibiotic agents.

Methods

S. aureus biofilms were grown on titanium discs (13 mm × 4 mm) in a bioreactor for 48 hours. Shockwaves were applied with either 250, 500, or 1,000 impulses onto the discs surrounded by either phosphate-buffered saline or antibiotic (rifampin alone or in combination with nafcillin). The number of viable bacteria was determined by quantitative culture after sonication. Representative samples were taken for scanning electron microscopy.


The Bone & Joint Journal
Vol. 103-B, Issue 2 | Pages 213 - 221
1 Feb 2021
Morgenstern M Kuehl R Zalavras CG McNally M Zimmerli W Burch MA Vandendriessche T Obremskey WT Verhofstad MHJ Metsemakers WJ

Aims

The principle strategies of fracture-related infection (FRI) treatment are debridement, antimicrobial therapy, and implant retention (DAIR) or debridement, antimicrobial therapy, and implant removal/exchange. Increasing the period between fracture fixation and FRI revision surgery is believed to be associated with higher failure rates after DAIR. However, a clear time-related cut-off has never been scientifically defined. This systematic review analyzed the influence of the interval between fracture fixation and FRI revision surgery on success rates after DAIR.

Methods

A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in PubMed (including MEDLINE), Embase, and Web of Science Core Collection, investigating the outcome after DAIR procedures of long bone FRIs in clinical studies published until January 2020.


The Bone & Joint Journal
Vol. 102-B, Issue 3 | Pages 336 - 344
1 Mar 2020
Ji B Li G Zhang X Wang Y Mu W Cao L

Aims

In the absence of an identified organism, single-stage revision is contraindicated in prosthetic joint infection (PJI). However, no studies have examined the use of intra-articular antibiotics in combination with single-stage revision in these cases. In this study, we present the results of single-stage revision using intra-articular antibiotic infusion for treating culture-negative (CN) PJI.

Methods

A retrospective analysis between 2009 and 2016 included 51 patients with CN PJI who underwent single-stage revision using intra-articular antibiotic infusion; these were compared with 192 culture-positive (CP) patients. CN patients were treated according to a protocol including intravenous vancomycin and a direct intra-articular infusion of imipenem and vancomycin alternately used in the morning and afternoon. In the CP patients, pathogen-sensitive intravenous (IV) antibiotics were administered for a mean of 16 days (12 to 21), and for resistant cases, additional intra-articular antibiotics were used. The infection healing rate, Harris Hip Score (HHS), and Hospital for Special Surgery (HSS) knee score were compared between CN and CP groups.


The Bone & Joint Journal
Vol. 102-B, Issue 6 Supple A | Pages 3 - 9
1 Jun 2020
Yang J Parvizi J Hansen EN Culvern CN Segreti JC Tan T Hartman CW Sporer SM Della Valle CJ

Aims

The aim of this study was to determine if a three-month course of microorganism-directed oral antibiotics reduces the rate of failure due to further infection following two-stage revision for chronic prosthetic joint infection (PJI) of the hip and knee.

Methods

A total of 185 patients undergoing a two-stage revision in seven different centres were prospectively enrolled. Of these patients, 93 were randomized to receive microorganism-directed oral antibiotics for three months following reimplantation; 88 were randomized to receive no antibiotics, and four were withdrawn before randomization. Of the 181 randomized patients, 28 were lost to follow-up, six died before two years follow-up, and five with culture negative infections were excluded. The remaining 142 patients were followed for a mean of 3.3 years (2.0 to 7.6) with failure due to a further infection as the primary endpoint. Patients who were treated with antibiotics were also assessed for their adherence to the medication regime and for side effects to antibiotics.


Bone & Joint Research
Vol. 9, Issue 11 | Pages 778 - 788
1 Nov 2020
Xu H Yang J Xie J Huang Z Huang Q Cao G Pei F

Aims

The efficacy and safety of intrawound vancomycin for preventing surgical site infection in primary hip and knee arthroplasty is uncertain.

Methods

A systematic review of the literature was conducted, indexed from inception to March 2020 in PubMed, Web of Science, Cochrane Library, Embase, and Google Scholar databases. All studies evaluating the efficacy and/or safety of intrawound vancomycin in patients who underwent primary hip and knee arthroplasty were included. Incidence of periprosthetic joint infection (PJI), superficial infection, aseptic wound complications, acute kidney injury, anaphylactic reaction, and ototoxicity were meta-analyzed. Results were reported as odds ratios (ORs) and 95% confidence intervals (CIs). The quality of included studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) assessment tool.


The Bone & Joint Journal
Vol. 101-B, Issue 1 | Pages 75 - 82
1 Jan 2019
Kim J Lee SY Jung JH Kim SW Oh J Park MS Chang H Kim T

Aims

The aim of this study was to evaluate the outcome of spinal instrumentation in haemodialyzed patients with native pyogenic spondylodiscitis. Spinal instrumentation in these patients can be dangerous due to rates of complications and mortality, and biofilm formation on the instrumentation.

Patients and Methods

A total of 134 haemodialyzed patients aged more than 50 years who underwent surgical treatment for pyogenic spondylodiscitis were included in the study. Their mean age was 66.4 years (50 to 83); 66 were male (49.3%) and 68 were female (50.7%). They were divided into two groups according to whether spinal instrumentation was used or not. Propensity score matching was used to attenuate the potential selection bias. The outcome of treatment was compared between these two groups.


Bone & Joint 360
Vol. 8, Issue 4 | Pages 5 - 13
1 Aug 2019
Middleton R Khan T Alvand A


The Bone & Joint Journal
Vol. 102-B, Issue 6 Supple A | Pages 176 - 180
1 Jun 2020
Lee G Colen DL Levin LS Kovach SJ

Aims

The integrity of the soft tissue envelope is crucial for successful treatment of infected total knee arthroplasty (TKA). The purpose of this study was to evaluate the rate of limb salvage, infection control, and clinical function following microvascular free flap coverage for salvage of the infected TKA.

Methods

We retrospectively reviewed 23 microvascular free tissue transfers for management of soft tissue defects in infected TKA. There were 16 men and seven women with a mean age of 61.2 years (39 to 81). The median number of procedures performed prior to soft tissue coverage was five (2 to 9) and all patients had failed at least one two-stage reimplantation procedure. Clinical outcomes were measured using the Knee Society Scoring system for pain and function.


The Bone & Joint Journal
Vol. 102-B, Issue 7 | Pages 852 - 860
1 Jul 2020
Zamora T Garbuz DS Greidanus NV Masri BA

Aims

Our objective is to describe our early and mid-term results with the use of a new simple primary knee prosthesis as an articulating spacer in planned two-stage management for infected knee arthroplasty. As a second objective, we compared outcomes between the group with a retained first stage and those with a complete two-stage revision.

Methods

We included 47 patients (48 knees) with positive criteria for infection, with a minimum two-year follow-up, in which a two-stage approach with an articulating spacer with new implants was used. Patients with infection control, and a stable and functional knee were allowed to retain the initial first-stage components. Outcomes recorded included: infection control rate, reoperations, final range of motion (ROM), and quality of life assessment (QoL) including Western Ontario and McMaster Universities osteoarthritis index, Knee Injury and Osteoarthritis Outcome Score, Oxford Knee Score, 12-Item Short-Form Health Survey questionnaire, and University of California Los Angeles (UCLA) activity score and satisfaction score. These outcomes were evaluated and compared to additional cohorts of patients with retained first-stage interventions and those with a complete two-stage revision. Mean follow-up was 3.7 years (2.0 to 6.5).


Bone & Joint Research
Vol. 9, Issue 7 | Pages 440 - 449
1 Jul 2020
Huang Z Li W Lee G Fang X Xing L Yang B Lin J Zhang W

Aims

The aim of this study was to evaluate the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens from synovial fluid of prosthetic joint infection (PJI) patients.

Methods

A group of 75 patients who underwent revision knee or hip arthroplasties were enrolled prospectively. Ten patients with primary arthroplasties were included as negative controls. Synovial fluid was collected for mNGS analysis. Optimal thresholds were determined to distinguish pathogens from background microbes. Synovial fluid, tissue, and sonicate fluid were obtained for culture.


Bone & Joint Research
Vol. 9, Issue 12 | Pages 884 - 893
1 Dec 2020
Guerado E Cano JR Pons-Palliser J

Aims

A systematic literature review focusing on how long before surgery concurrent viral or bacterial infections (respiratory and urinary infections) should be treated in hip fracture patients, and if there is evidence for delaying this surgery.

Methods

A total of 11 databases were examined using the COre, Standard, Ideal (COSI) protocol. Bibliographic searches (no chronological or linguistic restriction) were conducted using, among other methods, the Patient, Intervention, Comparison, Outcome (PICO) template. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines for flow diagram and checklist. Final reading of the complete texts was conducted in English, French, and Spanish. Classification of papers was completed within five levels of evidence (LE).


The Bone & Joint Journal
Vol. 102-B, Issue 3 | Pages 329 - 335
1 Mar 2020
Fink B Schuster P Braun R Tagtalianidou E Schlumberger M

Aims

Biopsy of the periprosthetic tissue is an important diagnostic tool for prosthetic joint infection (PJI) as it enables the detection of the responsible microorganism with its sensitivity to antibiotics. We aimed to investigate how often the bacteria identified in the tissue analysis differed between samples obtained from preoperative biopsy and intraoperative revision surgery in cases of late PJI; and whether there was a therapeutic consequence.

Methods

A total of 508 patients who required revision surgery of total hip arthroplasty (THA) (n = 231) or total knee arthroplasty (TKA) (n = 277) because of component loosening underwent biopsy before revision surgery. The tissue samples collected at biopsy and during revision surgery were analyzed according to the criteria of the Musculoskeletal Infection Society (MSIS).


Bone & Joint 360
Vol. 9, Issue 1 | Pages 28 - 32
1 Feb 2020


Bone & Joint Research
Vol. 9, Issue 8 | Pages 484 - 492
1 Aug 2020
Zhang W Fang X Shi T Cai Y Huang Z Zhang C Lin J Li W

Aims

To explore the effect of different types of articulating antibiotic-loaded cement spacers in two-stage revision for chronic hip prosthetic joint infection (PJI).

Methods

A retrospective cohort study was performed involving 36 chronic PJI patients treated with different types of articulating antibiotic-loaded cement spacers between January 2014 and December 2017. The incidence of complications and the therapeutic effects of different types of antibiotic-loaded articulating cement spacers were compared.


The Bone & Joint Journal
Vol. 101-B, Issue 4 | Pages 396 - 402
1 Apr 2019
Ji B Wahafu T Li G Zhang X Wang Y Momin M Cao L

Aims

Single-stage revision is not widely pursued due to restrictive inclusion criteria. In this study, we evaluated the results of single-stage revision of chronically infected total hip arthroplasty (THA) using broad inclusion criteria and cementless implants.

Patients and Methods

Between 2010 and 2016, 126 patients underwent routine single-stage revision with cementless reconstruction with powdered vancomycin or imipenem poured into the medullary cavity and re-implantation of cementless components. For patients with a culture-negative hip, fungal infections, and multidrug-resistant organisms, a direct intra-articular infusion of pathogen-sensitive antibiotics was performed postoperatively. Recurrence of infection and clinical outcomes were evaluated. Three patients died and 12 patients (none with known recurrent infection) were lost to follow-up. There were 111 remaining patients (60 male, 51 female) with a mean age of 58.7 (sd 12.7; 20 to 79).


The Bone & Joint Journal
Vol. 100-B, Issue 10 | Pages 1359 - 1363
1 Oct 2018
Chiu Y Chung T Wu C Tsai K Jou I Tu Y Ma C

Aims

This study reports the outcomes of a technique of soft-tissue coverage and Chopart amputation for severe crush injuries of the forefoot.

Patients and Methods

Between January 2012 to December 2016, 12 patients (nine male; three female, mean age 38.58 years; 26 to 55) with severe foot crush injury underwent treatment in our institute. All patients were followed-up for at least one year. Their medical records, imaging, visual analogue scale score, walking ability, complications, and functional outcomes one year postoperatively based on the American Orthopedic Foot and Ankle Society (AOFAS) and 36-Item Short-Form Health Survey (SF-36) scores were reviewed.