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Bone & Joint Research
Vol. 6, Issue 6 | Pages 391 - 398
1 Jun 2017
Lenguerrand E Whitehouse MR Beswick AD Jones SA Porter ML Blom* AW

Objectives. We used the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man (NJR) to investigate the risk of revision due to prosthetic joint infection (PJI) for patients undergoing primary and revision hip arthroplasty, the changes in risk over time, and the overall burden created by PJI. Methods. We analysed revision total hip arthroplasties (THAs) performed due to a diagnosis of PJI and the linked index procedures recorded in the NJR between 2003 and 2014. The cohort analysed consisted of 623 253 index primary hip arthroplasties, 63 222 index revision hip arthroplasties and 7585 revision THAs performed due to a diagnosis of PJI. The prevalence, cumulative incidence functions and the burden of PJI (total procedures) were calculated. Overall linear trends were investigated with log-linear regression. Results. We demonstrated a prevalence of revision THA due to prosthetic joint infection of 0.4/100 procedures following primary and 1.6/100 procedures following revision hip arthroplasty. The prevalence of revision due to PJI in the three months following primary hip arthroplasty has risen 2.3-fold (95% confidence interval (CI) 1.3 to 4.1) between 2005 and 2013, and 3.0-fold (95% CI 1.1 to 8.5) following revision hip arthroplasty. Over 1000 procedures are performed annually as a consequence of hip PJI, an increase of 2.6-fold between 2005 and 2013. Conclusions. Although the risk of revision due to PJI following hip arthroplasty is low, it is rising and, coupled with the established and further predicted increased incidence of both primary and revision hip arthroplasty, this represents a growing and substantial treatment burden. Cite this article: E. Lenguerrand, M. R. Whitehouse, A. D. Beswick, S. A. Jones, M. L. Porter, A. W. Blom. Revision for prosthetic joint infection following hip arthroplasty: Evidence from the National Joint Registry. Bone Joint Res 2017;6:391–398. DOI: 10.1302/2046-3758.66.BJR-2017-0003.R1


Bone & Joint Research
Vol. 8, Issue 4 | Pages 179 - 188
1 Apr 2019
Chen M Chang C Yang L Hsieh P Shih H Ueng SWN Chang Y

Objectives. Prosthetic joint infection (PJI) diagnosis is a major challenge in orthopaedics, and no reliable parameters have been established for accurate, preoperative predictions in the differential diagnosis of aseptic loosening or PJI. This study surveyed factors in synovial fluid (SF) for improving PJI diagnosis. Methods. We enrolled 48 patients (including 39 PJI and nine aseptic loosening cases) who required knee/hip revision surgery between January 2016 and December 2017. The PJI diagnosis was established according to the Musculoskeletal Infection Society (MSIS) criteria. SF was used to survey factors by protein array and enzyme-linked immunosorbent assay to compare protein expression patterns in SF among three groups (aseptic loosening and first- and second-stage surgery). We compared routine clinical test data, such as C-reactive protein level and leucocyte number, with potential biomarker data to assess the diagnostic ability for PJI within the same patient groups. Results. Cut-off values of 1473 pg/ml, 359 pg/ml, and 8.45 pg/ml were established for interleukin (IL)-16, IL-18, and cysteine-rich with EGF-like domains 2 (CRELD2), respectively. Receiver operating characteristic curve analysis showed that these factors exhibited an accuracy of 1 as predictors of PJI. These factors represent potential biomarkers for decisions associated with prosthesis reimplantation based on their ability to return to baseline values following the completion of debridement. Conclusion. IL-16, IL-18, and CRELD2 were found to be potential biomarkers for PJI diagnosis, with SF tests outperforming blood tests in accuracy. These factors could be useful for assessing successful debridement based on their ability to return to baseline values following the completion of debridement. Cite this article: M-F. Chen, C-H. Chang, L-Y. Yang, P-H. Hsieh, H-N. Shih, S. W. N. Ueng, Y. Chang. Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections. Bone Joint Res 2019;8:179–188. DOI: 10.1302/2046-3758.84.BJR-2018-0291.R1


Bone & Joint Research
Vol. 8, Issue 8 | Pages 367 - 377
1 Aug 2019
Chen M Chang C Chiang-Ni C Hsieh P Shih H Ueng SWN Chang Y

Objectives. Prosthetic joint infection (PJI) is the most common cause of arthroplasty failure. However, infection is often difficult to detect by conventional bacterial cultures, for which false-negative rates are 23% to 35%. In contrast, 16S rRNA metagenomics has been shown to quantitatively detect unculturable, unsuspected, and unviable pathogens. In this study, we investigated the use of 16S rRNA metagenomics for detection of bacterial pathogens in synovial fluid (SF) from patients with hip or knee PJI. Methods. We analyzed the bacterial composition of 22 SF samples collected from 11 patients with PJIs (first- and second-stage surgery). The V3 and V4 region of bacteria was assessed by comparing the taxonomic distribution of the 16S rDNA amplicons with microbiome sequencing analysis. We also compared the results of bacterial detection from different methods including 16S metagenomics, traditional cultures, and targeted Sanger sequencing. Results. Polymicrobial infections were not only detected, but also characterized at different timepoints corresponding to first- and second-stage exchange arthroplasty. Similar taxonomic distributions were obtained by matching sequence data against SILVA, Greengenes, and The National Center for Biotechnology Information (NCBI). All bacteria isolated from the traditional culture could be further identified by 16S metagenomics and targeted Sanger sequencing. Conclusion. The data highlight 16S rRNA metagenomics as a suitable and promising method to detect and identify infecting bacteria, most of which may be uncultivable. Importantly, the method dramatically reduces turnaround time to two days rather than approximately one week for conventional cultures. Cite this article: M-F. Chen, C-H. Chang, C. Chiang-Ni, P-H. Hsieh, H-N. Shih, S. W. N. Ueng, Y. Chang. Rapid analysis of bacterial composition in prosthetic joint infection by 16S rRNA metagenomic sequencing. Bone Joint Res 2019;8:367–377. DOI: 10.1302/2046-3758.88.BJR-2019-0003.R2


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. Results. A total of 49 PJI and 21 noninfection patients were finally included. Of the 39 culture-positive PJI cases, mNGS results were positive in 37 patients (94.9%), and were consistent with culture results at the genus level in 32 patients (86.5%) and at the species level in 27 patients (73.0%). Metagenomic next-generation sequencing additionally identified 15 pathogens from five culture-positive and all ten culture-negative PJI cases, and even one pathogen from one noninfection patient, while yielding no positive findings in any primary arthroplasty. However, seven pathogens identified by culture were missed by mNGS. The sensitivity of mNGS for diagnosing PJI was 95.9%, which was significantly higher than that of comprehensive culture (79.6%; p = 0.014). The specificity is similar between mNGS and comprehensive culture (95.2% and 95.2%, respectively; p = 1.0). Conclusion. Metagenomic next-generation sequencing can effectively identify pathogens from synovial fluid of PJI patients, and demonstrates high accuracy in diagnosing PJI. Cite this article: Bone Joint Res 2020;9(7):440–449


Bone & Joint Research
Vol. 8, Issue 11 | Pages 526 - 534
1 Nov 2019
Yang C Wang J Yin Z Wang Q Zhang X Jiang Y Shen H

Objectives. The optimal protocol for antibiotic loading in the articulating cement spacers for the treatment of prosthetic joint infection (PJI) remains controversial. The objective of the present study was to investigate the effectiveness of articulating cement spacers loaded with a new combination of antibiotics. Methods. A retrospective cohort study involving 114 PJI cases treated with implantation of an articulating cement spacer between 2005 and 2016 was performed. The treatment outcomes of the conventional protocol (i.e. gentamicin and vancomycin (GV protocol)) were compared with those reported using the sophisticated antibiotic-loading protocol (i.e. vancomycin, meropenem, and amphotericin (VMA protocol)). Results. There were 62 and 52 PJI cases treated with the GV and VMA protocols, respectively. Antimicrobial susceptibility testing revealed that 22/78 of all isolates (28.2%) in this series were resistant to gentamicin, whereas there were no vancomycin-, meropenem-, or amphotericin-resistant strains. The overall infection recurrence rates were 17.7% (11/62) and 1.9% (1/52), respectively (p = 0.006). In patients with a negative preoperative culture, there was no infection recurrence reported in the VMA cohort (0/45 (0%) vs 10/54 (18.5%) in the GV cohort; p = 0.002). Multivariate analysis indicated that the VMA protocol correlated with a decreased risk of infection recurrence compared with the GV protocol (p = 0.025). Conclusion. The sophisticated VMA protocol for the loading of antibiotics in articulating cement spacers, as part of a two-stage exchange, was associated with a reduced rate of infection recurrence. This proposed protocol appears to be safe and effective, especially in patients with negative culture results prior to the first-stage operation. Cite this article: Bone Joint Res 2019;8:526–534


Bone & Joint Research
Vol. 8, Issue 11 | Pages 526 - 534
1 Nov 2019
Yang C Wang J Yin Z Wang Q Zhang X Jiang Y Shen H

Objectives. The optimal protocol for antibiotic loading in the articulating cement spacers for the treatment of prosthetic joint infection (PJI) remains controversial. The objective of the present study was to investigate the effectiveness of articulating cement spacers loaded with a new combination of antibiotics. Methods. A retrospective cohort study involving 114 PJI cases treated with implantation of an articulating cement spacer between 2005 and 2016 was performed. The treatment outcomes of the conventional protocol (i.e. gentamicin and vancomycin (GV protocol)) were compared with those reported using the sophisticated antibiotic-loading protocol (i.e. vancomycin, meropenem, and amphotericin (VMA protocol)). Results. There were 62 and 52 PJI cases treated with the GV and VMA protocols, respectively. Antimicrobial susceptibility testing revealed that 22/78 of all isolates (28.2%) in this series were resistant to gentamicin, whereas there were no vancomycin-, meropenem-, or amphotericin-resistant strains. The overall infection recurrence rates were 17.7% (11/62) and 1.9% (1/52), respectively (p = 0.006). In patients with a negative preoperative culture, there was no infection recurrence reported in the VMA cohort (0/45 (0%) vs 10/54 (18.5%) in the GV cohort; p = 0.002). Multivariate analysis indicated that the VMA protocol correlated with a decreased risk of infection recurrence compared with the GV protocol (p = 0.025). Conclusion. The sophisticated VMA protocol for the loading of antibiotics in articulating cement spacers, as part of a two-stage exchange, was associated with a reduced rate of infection recurrence. This proposed protocol appears to be safe and effective, especially in patients with negative culture results prior to the first-stage operation. Cite this article: Bone Joint Res 2019;8:526–534


Bone & Joint Research
Vol. 9, Issue 5 | Pages 202 - 210
1 May 2020
Trotter AJ Dean R Whitehouse CE Mikalsen J Hill C Brunton-Sim R Kay GL Shakokani M Durst AZE Wain J McNamara I O’Grady J

Aims. This pilot study tested the performance of a rapid assay for diagnosing prosthetic joint infection (PJI), which measures synovial fluid calprotectin from total hip and knee revision patients. Methods. A convenience series of 69 synovial fluid samples from revision patients at the Norfolk and Norwich University Hospital were collected intraoperatively (52 hips, 17 knees) and frozen. Synovial fluid calprotectin was measured retrospectively using a new commercially available lateral flow assay for PJI diagnosis (Lyfstone AS) and compared to International Consensus Meeting (ICM) 2018 criteria and clinical case review (ICM-CR) gold standards. Results. According to ICM, 24 patients were defined as PJI positive and the remaining 45 were negative. The overall accuracy of the lateral flow test compared to ICM was 75.36% (52/69, 95% CI 63.51% to 84.95%), sensitivity and specificity were 75.00% (18/24, 95% CI 53.29% to 90.23%) and 75.56% (34/45, 95% CI 60.46% to 87.12%), respectively, positive predictive value (PPV) was 62.07% (18/29, 95% CI 48.23% to 74.19%) and negative predictive value (NPV) was 85.00% (34/40, 95% CI 73.54% to 92.04%), and area under the receiver operating characteristic (ROC) curve (AUC) was 0.78 (95% CI 0.66 to 0.87). Patient data from discordant cases were reviewed by the clinical team to develop the ICM-CR gold standard. The lateral flow test performance improved significantly when compared to ICM-CR, with accuracy increasing to 82.61% (57/69, 95% CI 71.59% to 90.68%), sensitivity increasing to 94.74% (18/19, 95% CI 73.97% to 99.87%), NPV increasing to 97.50% (39/40, 95% CI 85.20% to 99.62%), and AUC increasing to 0.91 (95% CI 0.81 to 0.96). Test performance was better in knees (100.00% accurate (17/17, 95% CI 80.49% to 100.00%)) compared to hips (76.92% accurate (40/52, 95% CI 63.16% to 87.47%)). Conclusion. This study demonstrates that the calprotectin lateral flow assay could be an effective diagnostic test for PJI, however additional prospective studies testing fresh samples are required. Cite this article:Bone Joint Res. 2020;9(5):202–210


Bone & Joint Research
Vol. 9, Issue 9 | Pages 587 - 592
5 Sep 2020
Qin L Li X Wang J Gong X Hu N Huang W

Aims. This study aimed to explore whether serum combined with synovial interleukin-6 (IL-6) measurement can improve the accuracy of prosthetic joint infection (PJI) diagnosis, and to establish the cut-off values of IL-6 in serum and synovial fluid in detecting chronic PJI. Methods. Patients scheduled to have a revision surgery for indications of chronic infection of knee and hip arthroplasties or aseptic loosening of an implant were prospectively screened before being enrolled into this study. The Musculoskeletal Infection Society (MSIS) definition of PJI was used for the classification of cases as aseptic or infected. Serum CRP, ESR, IL-6, and percentage of polymorphonuclear neutrophils (PMN%) and IL-6 in synovial fluid were analyzed. Statistical tests were performed to compare these biomarkers in the two groups, and receiver operating characteristic (ROC) curves and area under the curve (AUC) were analyzed for each biomarker. Results. A total of 93 patients were enrolled. There was no difference in demographic data between both groups. Synovial fluid IL-6, with a threshold of 1,855.36 pg/ml, demonstrated a mean sensitivity of 94.59% (95% confidence interval (CI) 81.8% to 99.3%) and a mean specificity of 92.86% (95% CI 82.7 to 98.0) for detecting chronic PJI. Then 6.7 pg/ml was determined to be the optimal threshold value of serum IL-6 for the diagnosis of chronic PJI, with a mean sensitivity of 97.30% (95% CI 85.8% to 99.9%) and a mean specificity of 76.79% (95% CI 63.6% to 87.0%). The combination of synovial IL-6 and serum IL-6 led to improved accuracy of 96.77% in diagnosing chronic PJI. Conclusion. The present study identified that a combination of IL-6 in serum and synovial IL-6 has the potential for further improvement of the diagnosis of PJI. Cite this article: Bone Joint Res 2020;9(9):587–592


Bone & Joint Research
Vol. 9, Issue 5 | Pages 219 - 224
1 May 2020
Yang B Fang X Cai Y Yu Z Li W Zhang C Huang Z Zhang W

Aims. Preoperative diagnosis is important for revision surgery after prosthetic joint infection (PJI). The purpose of our study was to determine whether reverse transcription-quantitative polymerase chain reaction (RT-qPCR), which is used to detect bacterial ribosomal RNA (rRNA) preoperatively, can reveal PJI in low volumes of aspirated fluid. Methods. We acquired joint fluid samples (JFSs) by preoperative aspiration from patients who were suspected of having a PJI and failed arthroplasty; patients with preoperative JFS volumes less than 5 ml were enrolled. RNA-based polymerase chain reaction (PCR) and bacterial culture were performed, and diagnostic efficiency was compared between the two methods.According to established Musculoskeletal Infection Society (MSIS) criteria, 21 of the 33 included patients were diagnosed with PJI. Results. RNA-based PCR exhibited 57.1% sensitivity, 91.7% specificity, 69.7% accuracy, 92.3% positive predictive value, and 55.0% negative predictive value. The corresponding values for culture were 28.6%, 83.3%, 48.5%, 75.0%, and 40.0%, respectively. A significantly higher sensitivity was thus obtained with the PCR method versus the culture method. Conclusion. In situations in which only a small JFS volume can be acquired, RNA-based PCR analysis increases the utility of preoperative puncture for patients who require revision surgery due to suspected PJI. Cite this article:Bone Joint Res. 2020;9(5):219–224


Bone & Joint Research
Vol. 9, Issue 6 | Pages 311 - 313
1 Jun 2020
Tsang SJ Morgan-Jones R Simpson AHRW


Bone & Joint Research
Vol. 9, Issue 8 | Pages 450 - 456
1 Aug 2020
Zhang Z Cai Y Bai G Zhang C Li W Yang B Zhang W

Aims. This study aimed to evaluate calprotectin in synovial fluid for diagnosing chronic prosthetic joint infection (PJI) . Methods. A total of 63 patients who were suspected of PJI were enrolled. The synovial fluid calprotectin was tested by an enzyme-linked immunosorbent assay (ELISA). Laboratory test data, such as ESR, CRP, synovial fluid white blood cells (SF-WBCs), and synovial fluid polymorphonuclear cells (SF-PMNs), were documented. Chi-squared tests were used to compare the sensitivity and specificity of calprotectin and laboratory tests. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve was calculated to determine diagnostic efficacy. Results. The median calprotectin level was 776 μg/ml (interquartile range (IQR) 536.5 to 1132) in the PJI group and 54.5 μg/ml (IQR, 38.75 to 78.25) in the aseptic failure (AF) group (p < 0.05). Using a threshold of 173 ug/ml, the sensitivity was 95.2%, with a 97.6% specificity, and the AUC was 0.993. The sensitivity of calprotectin of the antibiotic-treated PJI group was 100% versus 90.9% of the non-antibiotic-treated PJI group. Although 47.6% (ten cases) of the patients in the PJI group received antibiotics before aspiration, the diagnostic efficacy of calprotectin was not affected. The sensitivity and specificity of ESR, CRP, SF-WBCs, and SF-PMNs ranged from 76.2% to 90.5% and 64.3% to 85.7%, respectively. Conclusion. Calprotectin in synovial fluid has great diagnostic efficacy for PJI diagnosisand outperformed ESR, CRP, SF-WBCs, and SF-PMNs. Cite this article: Bone Joint Res 2020;9(8):450–456


Bone & Joint Research
Vol. 8, Issue 11 | Pages 570 - 572
1 Nov 2019
Ahmed SS Haddad FS


Aims. Methicillin-resistant Staphylococcus aureus (MRSA) can cause wound infections via a ‘Trojan Horse’ mechanism, in which neutrophils engulf intestinal MRSA and travel to the wound, releasing MRSA after apoptosis. The possible role of intestinal MRSA in prosthetic joint infection (PJI) is unknown. Methods. Rats underwent intestinal colonization with green fluorescent protein (GFP)-tagged MRSA by gavage and an intra-articular wire was then surgically implanted. After ten days, the presence of PJI was determined by bacterial cultures of the distal femur, joint capsule, and implant. We excluded several other possibilities for PJI development. Intraoperative contamination was excluded by culturing the specimen obtained from surgical site. Extracellular bacteraemia-associated PJI was excluded by comparing with the infection rate after intravenous injection of MRSA or MRSA-carrying neutrophils. To further support this theory, we tested the efficacy of prophylactic membrane-permeable and non-membrane-permeable antibiotics in this model. Results. After undergoing knee surgery eight or 72 hours after colonization, five out of 20 rats (25.0%) and two out of 20 rats (10.0%) developed PJI, respectively. Strikingly, 11 out of 20 rats (55.0%) developed PJI after intravenous injection of MRSA-carrying neutrophils that were isolated from rats with intestinal MRSA colonization. None of the rats receiving intravenous injections of MRSA developed PJI. These results suggest that intestinal MRSA carried by neutrophils could cause PJI in our rat model. Ten out of 20 (50.0%) rats treated with non-membrane-permeable gentamicin developed PJI, whereas only one out of 20 (5.0%) rats treated with membrane-permeable linezolid developed PJI. Conclusion. Neutrophils as carriers of intestinal MRSA may play an important role in PJI development. Cite this article:Bone Joint Res. 2020;9(4):152–161


Bone & Joint Research
Vol. 9, Issue 2 | Pages 79 - 81
1 Feb 2020
Alt V Rupp M Langer M Baumann F Trampuz A

Cite this article: Bone Joint Res. 2020;9(2):79–81.


Bone & Joint Research
Vol. 9, Issue 2 | Pages 77 - 78
1 Feb 2020
Alt V Rupp M Langer M Baumann F Trampuz A

Cite this article: Bone Joint Res. 2020;9(2):77–78.


Bone & Joint Research
Vol. 13, Issue 7 | Pages 353 - 361
10 Jul 2024
Gardete-Hartmann S Mitterer JA Sebastian S Frank BJH Simon S Huber S Löw M Sommer I Prinz M Halabi M Hofstaetter JG

Aims

This study aimed to evaluate the BioFire Joint Infection (JI) Panel in cases of hip and knee periprosthetic joint infection (PJI) where conventional microbiology is unclear, and to assess its role as a complementary intraoperative diagnostic tool.

Methods

Five groups representing common microbiological scenarios in hip and knee revision arthroplasty were selected from our arthroplasty registry, prospectively maintained PJI databases, and biobank: 1) unexpected-negative cultures (UNCs), 2) unexpected-positive cultures (UPCs), 3) single-positive intraoperative cultures (SPCs), and 4) clearly septic and 5) aseptic cases. In total, 268 archived synovial fluid samples from 195 patients who underwent acute/chronic revision total hip or knee arthroplasty were included. Cases were classified according to the International Consensus Meeting 2018 criteria. JI panel evaluation of synovial fluid was performed, and the results were compared with cultures.


Bone & Joint Research
Vol. 9, Issue 4 | Pages 192 - 199
1 Apr 2020
Pijls BG Sanders IMJG Kujiper EJ Nelissen RGHH

Aims

Induction heating is a noninvasive, nonantibiotic treatment modality that can potentially be used to cause thermal damage to the bacterial biofilm on the metal implant surface. The purpose of this study was to determine the effectiveness of induction heating on killing Staphylococcus epidermidis from biofilm and to determine the possible synergistic effect of induction heating and antibiotics.

Methods

S. epidermidis biofilms were grown on titanium alloy (Ti6Al4V) coupons for 24 hours (young biofilm) and seven days (mature biofilm). These coupons with biofilm were heated to temperatures of 50°C, 55°C, 60°C, 65°C, 70°C, 80°C, and 90°C for 3.5 minutes and subsequently exposed to vancomycin and rifampicin at clinically relevant concentrations.


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. Results. A total of 36 patients with chronic hip PJI were included. Of these, 13 patients were treated with spacers with Kirschner wires as an endoskeleton (group I), ten patients were treated with spacers with a cemented femoral prosthesis as an endoskeleton (group II), and 13 patients were treated with cemented femoral prostheses combined with polyethylene sockets as a spacer (group III). All patients were followed for 12 to 60 months, with a mean follow-up period of 26.44 months (SEM 14.09). Infection was controlled in 34 patients (94.44%), and there were no significant differences in the eradication rate among the three groups (p = 0.705), but the risk of complications related to the spacer in group III was significantly lower than that in groups I and II (p = 0.006). Conclusion. Articulating antibiotic-loaded cement spacers is effective in the treatment of chronic hip PJI, but we must pay attention to the occurrence of spacer fracture and dislocation, which can lead to poor joint function. The risk of spacer-related mechanical complications is low, and better joint function can be achieved when using cemented femoral prostheses combined with polyethylene sockets as spacers. Cite this article: Bone Joint Res 2020;9(8):484–492


Bone & Joint Research
Vol. 9, Issue 10 | Pages 635 - 644
1 Oct 2020
Lemaignen A Grammatico-Guillon L Astagneau P Marmor S Ferry T Jolivet-Gougeon A Senneville E Bernard L

Aims. The French registry for complex bone and joint infections (C-BJIs) was created in 2012 in order to facilitate a homogeneous management of patients presented for multidisciplinary advice in referral centres for C-BJI, to monitor their activity and to produce epidemiological data. We aimed here to present the genesis and characteristics of this national registry and provide the analysis of its data quality. Methods. A centralized online secured database gathering the electronic case report forms (eCRFs) was filled for every patient presented in multidisciplinary meetings (MM) among the 24 French referral centres. Metrics of this registry were described between 2012 and 2016. Data quality was assessed by comparing essential items from the registry with a controlled dataset extracted from medical charts of a random sample of patients from each centre. Internal completeness and consistency were calculated. Results. Between 2012 and 2016, 30,607 presentations in MM were recorded corresponding to 17,748 individual patients (mean age 62.1 years (SD 18.4); 10,961 (61.8%) males). BJI was considered as complex for 63% of cases (n = 19,355), and 13,376 (44%) had prosthetic joint infections (PJIs). The controlled dataset, available for 19 centres, included 283 patients. Global consistency and completeness were estimated at 88.2% and 88.9%, respectively, considering missing items in the eCRFs as negative results. Conclusion. This national registry is one of the largest prospective databases on BJI and its acceptable data quality parameters allow further use for epidemiological purposes. Cite this article: Bone Joint Res 2020;9(9):635–644


Bone & Joint Research
Vol. 9, Issue 5 | Pages 211 - 218
1 May 2020
Hashimoto A Miyamoto H Kobatake T Nakashima T Shobuike T Ueno M Murakami T Noda I Sonohata M Mawatari M

Aims. Biofilm formation is intrinsic to prosthetic joint infection (PJI). In the current study, we evaluated the effects of silver-containing hydroxyapatite (Ag-HA) coating and vancomycin (VCM) on methicillin-resistant Staphylococcus aureus (MRSA) biofilm formation. Methods. Pure titanium discs (Ti discs), Ti discs coated with HA (HA discs), and 3% Ag-HA discs developed using a thermal spraying were inoculated with MRSA suspensions containing a mean in vitro 4.3 (SD 0.8) x 10. 6. or 43.0 (SD 8.4) x 10. 5. colony-forming units (CFUs). Immediately after MRSA inoculation, sterile phosphate-buffered saline or VCM (20 µg/ml) was added, and the discs were incubated for 24 hours at 37°C. Viable cell counting, 3D confocal laser scanning microscopy with Airyscan, and scanning electron microscopy were then performed. HA discs and Ag HA discs were implanted subcutaneously in vivo in the dorsum of rats, and MRSA suspensions containing a mean in vivo 7.2 (SD 0.4) x 10. 6.   or 72.0 (SD 4.2) x 10. 5.   CFUs were inoculated on the discs. VCM was injected subcutaneously daily every 12 hours followed by viable cell counting. Results. Biofilms that formed on HA discs were thicker and larger than those on Ti discs, whereas those on Ag-HA discs were thinner and smaller than those on Ti discs. Viable bacterial counts in vivo revealed that Ag-HA combined with VCM was the most effective treatment. Conclusion. Ag-HA with VCM has a potential synergistic effect in reducing MRSA biofilm formation and can thus be useful for preventing and treating PJI. Cite this article:Bone Joint Res. 2020;9(5):211–218


Bone & Joint Research
Vol. 8, Issue 8 | Pages 387 - 396
1 Aug 2019
Alt V Rupp M Lemberger K Bechert T Konradt T Steinrücke P Schnettler R Söder S Ascherl R

Objectives. Preclinical data showed poly(methyl methacrylate) (PMMA) loaded with microsilver to be effective against a variety of bacteria. The purpose of this study was to assess patient safety of PMMA spacers with microsilver in prosthetic hip infections in a prospective cohort study. Methods. A total of 12 patients with prosthetic hip infections were included for a three-stage revision procedure. All patients received either a gentamicin-PMMA spacer (80 g to 160 g PMMA depending on hip joint dimension) with additional loading of 1% (w/w) of microsilver (0.8 g to 1.6 g per spacer) at surgery 1 followed by a gentamicin-PMMA spacer without microsilver at surgery 2 or vice versa. Implantation of the revision prosthesis was carried out at surgery 3. Results. In total, 11 of the 12 patients completed the study. No argyria or considerable differences in laboratory parameters were detected. Silver blood concentrations were below or around the detection limit of 1 ppb in ten of the 11 patients. A maximum of 5.6 ppb at 48 hours after implantation of the silver spacer, which is below the recommended maximum level of 10 ppb, was found in one patient. No silver was detected in the urine. Drainage fluids showed concentrations between 16.1 ppb and 23.3 ppb at 12 hours after implantation of the silver spacers, and between 16.8 ppb to 25.1 ppb at 48 hours after implantation. Pathohistological assessment of the periprosthetic membrane did not reveal any differences between the two groups. Conclusion. Microsilver-loaded gentamicin-PMMA spacers showed good biocompatibility and the broad antimicrobial activity warrants further clinical research to assess its effectivity in reducing infection rates in prosthetic joint infection. Cite this article: V. Alt, M. Rupp, K. Lemberger, T. Bechert, T. Konradt, P. Steinrücke, R. Schnettler, S. Söder, R. Ascherl. Safety assessment of microsilver-loaded poly(methyl methacrylate) (PMMA) cement spacers in patients with prosthetic hip infections: Results of a prospective cohort study. Bone Joint Res 2019;8:387–396. DOI: 10.1302/2046-3758.88.BJR-2018-0270.R1


Bone & Joint Research
Vol. 7, Issue 11 | Pages 609 - 619
1 Nov 2018
Pijls BG Sanders IMJG Kuijper EJ Nelissen RGHH

Objectives. Prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasty. Non-contact induction heating of metal implants is a new and emerging treatment for PJI. However, there may be concerns for potential tissue necrosis. It is thought that segmental induction heating can be used to control the thermal dose and to limit collateral thermal injury to the bone and surrounding tissues. The purpose of this study was to determine the thermal dose, for commonly used metal implants in orthopaedic surgery, at various distances from the heating centre (HC). Methods. Commonly used metal orthopaedic implants (hip stem, intramedullary nail, and locking compression plate (LCP)) were heated segmentally using an induction heater. The thermal dose was expressed in cumulative equivalent minutes at 43°C (CEM43) and measured with a thermal camera at several different distances from the HC. A value of 16 CEM43 was used as the threshold for thermal damage in bone. Results. Despite high thermal doses at the HC (7161 CEM43 to 66 640 CEM43), the thermal dose at various distances from the HC was lower than 16 CEM43 for the hip stem and nail. For the fracture plate without corresponding metal screws, doses higher than 16 CEM43 were measured up to 5 mm from the HC. Conclusion. Segmental induction heating concentrates the thermal dose at the targeted metal implant areas and minimizes collateral thermal injury by using the non-heated metal as a heat sink. Implant type and geometry are important factors to consider, as they influence dissipation of heat and associated collateral thermal injury. Cite this article: B. G. Pijls, I. M. J. G. Sanders, E. J. Kuijper, R. G. H. H. Nelissen. Segmental induction heating of orthopaedic metal implants. Bone Joint Res 2018;7:609–619. DOI: 10.1302/2046-3758.711.BJR-2018-0080.R1


Bone & Joint Research
Vol. 11, Issue 11 | Pages 787 - 802
1 Nov 2022
Sebastian S Tandberg F Liu Y Raina DB Tägil M Collin M Lidgren L

Aims

There is a lack of biomaterial-based carriers for the local delivery of rifampicin (RIF), one of the cornerstone second defence antibiotics for bone infections. RIF is also known for causing rapid development of antibiotic resistance when given as monotherapy. This in vitro study evaluated a clinically used biphasic calcium sulphate/hydroxyapatite (CaS/HA) biomaterial as a carrier for dual delivery of RIF with vancomycin (VAN) or gentamicin (GEN).

Methods

The CaS/HA composites containing RIF/GEN/VAN, either alone or in combination, were first prepared and their injectability, setting time, and antibiotic elution profiles were assessed. Using a continuous disk diffusion assay, the antibacterial behaviour of the material was tested on both planktonic and biofilm-embedded forms of standard and clinical strains of Staphylococcus aureus for 28 days. Development of bacterial resistance to RIF was determined by exposing the biofilm-embedded bacteria continuously to released fractions of antibiotics from CaS/HA-antibiotic composites.


Bone & Joint Research
Vol. 9, Issue 10 | Pages 701 - 708
1 Oct 2020
Chen X Li H Zhu S Wang Y Qian W

Aims

The diagnosis of periprosthetic joint infection (PJI) has always been challenging. Recently, D-dimer has become a promising biomarker in diagnosing PJI. However, there is controversy regarding its diagnostic value. We aim to investigate the diagnostic value of D-dimer in comparison to ESR and CRP.

Methods

PubMed, Embase, and the Cochrane Library were searched in February 2020 to identify articles reporting on the diagnostic value of D-dimer on PJI. Pooled analysis was conducted to investigate the diagnostic value of D-dimer, CRP, and ESR.


Bone & Joint Research
Vol. 9, Issue 9 | Pages 623 - 632
5 Sep 2020
Jayadev C Hulley P Swales C Snelling S Collins G Taylor P Price A

Aims

The lack of disease-modifying treatments for osteoarthritis (OA) is linked to a shortage of suitable biomarkers. This study combines multi-molecule synovial fluid analysis with machine learning to produce an accurate diagnostic biomarker model for end-stage knee OA (esOA).

Methods

Synovial fluid (SF) from patients with esOA, non-OA knee injury, and inflammatory knee arthritis were analyzed for 35 potential markers using immunoassays. Partial least square discriminant analysis (PLS-DA) was used to derive a biomarker model for cohort classification. The ability of the biomarker model to diagnose esOA was validated by identical wide-spectrum SF analysis of a test cohort of ten patients with esOA.


Bone & Joint Research
Vol. 9, Issue 5 | Pages 236 - 241
1 May 2020
Li R Wang C Ji X Zheng Q Li X Ni M Zhang G Chen J

Aims

The purpose of this study was to validate our hypothesis that centrifugation may eliminate false-positive leucocyte esterase (LE) strip test results caused by autoimmune diseases in the diagnosis of knee infection.

Methods

Between January 2016 and May 2019, 83 cases, including 33 cases of septic arthritis and 50 cases of aseptic arthritis, were enrolled in this study. To further validate our hypothesis, another 34 cases of inflammatory arthritis from the Department of Rheumatology of our institution were also included. After aspiration, one drop of synovial fluid was applied to LE strips before and after centrifugation. The results were recorded after approximately three minutes according to the different colour grades on the colour chart. The differences of LE results between each cohort were analyzed.


Bone & Joint Research
Vol. 8, Issue 5 | Pages 199 - 206
1 May 2019
Romanò CL Tsuchiya H Morelli I Battaglia AG Drago L

Implant-related infection is one of the leading reasons for failure in orthopaedics and trauma, and results in high social and economic costs. Various antibacterial coating technologies have proven to be safe and effective both in preclinical and clinical studies, with post-surgical implant-related infections reduced by 90% in some cases, depending on the type of coating and experimental setup used. Economic assessment may enable the cost-to-benefit profile of any given antibacterial coating to be defined, based on the expected infection rate with and without the coating, the cost of the infection management, and the cost of the coating. After reviewing the latest evidence on the available antibacterial coatings, we quantified the impact caused by delaying their large-scale application. Considering only joint arthroplasties, our calculations indicated that for an antibacterial coating, with a final user’s cost price of €600 and able to reduce post-surgical infection by 80%, each year of delay to its large-scale application would cause an estimated 35 200 new cases of post-surgical infection in Europe, equating to additional hospital costs of approximately €440 million per year. An adequate reimbursement policy for antibacterial coatings may benefit patients, healthcare systems, and related research, as could faster and more affordable regulatory pathways for the technologies still in the pipeline. This could significantly reduce the social and economic burden of implant-related infections in orthopaedics and trauma.

Cite this article: C. L. Romanò, H. Tsuchiya, I. Morelli, A. G. Battaglia, L. Drago. Antibacterial coating of implants: are we missing something? Bone Joint Res 2019;8:199–206. DOI: 10.1302/2046-3758.85.BJR-2018-0316.


Bone & Joint Research
Vol. 9, Issue 3 | Pages 120 - 129
1 Mar 2020
Guofeng C Chen Y Rong W Ruiyu L Kunzheng W

Aims

Patients with metabolic syndrome (MetS) are known to be at increased risk of postoperative complications, but it is unclear whether MetS is also associated with complications after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Here, we perform a systematic review and meta-analysis linking MetS to postoperative complications in THA and TKA.

Methods

The PubMed, OVID, and ScienceDirect databases were comprehensively searched and studies were selected and analyzed according to the guidelines of the Meta-analysis of Observational Studies in Epidemiology (MOOSE). We assessed the methodological quality of each study using the Newcastle-Ottawa Scale (NOS), and we evaluated the quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Data were extracted and meta-analyzed or qualitatively synthesized for several outcomes.


Bone & Joint Research
Vol. 8, Issue 2 | Pages 49 - 54
1 Feb 2019
Stravinskas M Nilsson M Vitkauskiene A Tarasevicius S Lidgren L

Objectives

The aim of this study was to analyze drain fluid, blood, and urine simultaneously to follow the long-term release of vancomycin from a biphasic ceramic carrier in major hip surgery. Our hypothesis was that there would be high local vancomycin concentrations during the first week with safe low systemic trough levels and a complete antibiotic release during the first month.

Methods

Nine patients (six female, three male; mean age 75.3 years (sd 12.3; 44 to 84)) with trochanteric hip fractures had internal fixations. An injectable ceramic bone substitute, with hydroxyapatite in a calcium sulphate matrix, containing 66 mg of vancomycin per millilitre, was inserted to augment the fixation. The vancomycin elution was followed by simultaneously collecting drain fluid, blood, and urine.


Bone & Joint Research
Vol. 8, Issue 7 | Pages 304 - 312
1 Jul 2019
Nicholson JA Tsang STJ MacGillivray TJ Perks F Simpson AHRW

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”.


Bone & Joint Research
Vol. 7, Issue 10 | Pages 570 - 579
1 Oct 2018
Kallala R Harris WE Ibrahim M Dipane M McPherson E

Aims

Calcium sulphate has traditionally been used as a filler of dead space arising during surgery. Various complications have been described following the use of Stimulan bio-absorbable calcium sulphate beads. This study is a prospective observational study to assess the safety profile of these beads when used in revision arthroplasty, comparing the complication rates with those reported in the literature.

Methods

A total of 755 patients who underwent 456 revision total knee arthroplasties (TKA) and 299 revision total hip arthroplasties (THA), with a mean follow-up of 35 months (0 to 78) were included in the study.


Objectives

Irrigation is the cornerstone of treating skeletal infection by eliminating pathogens in wounds. A previous study shows that irrigation with normal saline (0.9%) and ethylenediaminetetraacetic acid (EDTA) could improve the removal of Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) compared with normal saline (NS) alone. However, it is still unclear whether EDTA solution is effective against infection with drug-resistant bacteria.

Methods

We established three wound infection models (skin defect, bone-exposed, implant-exposed) by inoculating the wounds with a variety of representative drug-resistant bacteria including methicillin-resistant S. aureus (MRSA), extended spectrum beta-lactamase-producing E. coli (ESBL-EC), multidrug-resistant Pseudomonas aeruginosa (MRPA), vancomycin-resistant Enterococcus (VRE), multidrug-resistant Acinetobacter baumannii (MRAB), multidrug-resistant Enterobacter (MRE), and multidrug-resistant Proteus mirabilis (MRPM). Irrigation and debridement were repeated until the wound culture became negative. The operating times required to eliminate pathogens in wounds were compared through survival analysis.


Bone & Joint Research
Vol. 8, Issue 2 | Pages 81 - 89
1 Feb 2019
Funk GA Menuey EM Cole KA Schuman TP Kilway KV McIff TE

Objectives

The objective of this study was to characterize the effect of rifampin incorporation into poly(methyl methacrylate) (PMMA) bone cement. While incompatibilities between the two materials have been previously noted, we sought to identify and quantify the cause of rifampin’s effects, including alterations in curing properties, mechanical strength, and residual monomer content.

Methods

Four cement groups were prepared using commercial PMMA bone cement: a control; one with 1 g of rifampin; and one each with equimolar amounts of ascorbic acid or hydroquinone relative to the amount of rifampin added. The handling properties, setting time, exothermic output, and monomer loss were measured throughout curing. The mechanical strength of each group was tested over 14 days. A radical scavenging assay was used to assess the scavenging abilities of rifampin and its individual moieties.


Bone & Joint Research
Vol. 7, Issue 1 | Pages 79 - 84
1 Jan 2018
Tsang STJ McHugh MP Guerendiain D Gwynne PJ Boyd J Simpson AHRW Walsh TS Laurenson IF Templeton KE

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.


Bone & Joint Research
Vol. 5, Issue 9 | Pages 427 - 435
1 Sep 2016
Stravinskas M Horstmann P Ferguson J Hettwer W Nilsson M Tarasevicius S Petersen MM McNally MA Lidgren L

Objectives

Deep bone and joint infections (DBJI) are directly intertwined with health, demographic change towards an elderly population, and wellbeing.

The elderly human population is more prone to acquire infections, and the consequences such as pain, reduced quality of life, morbidity, absence from work and premature retirement due to disability place significant burdens on already strained healthcare systems and societal budgets.

DBJIs are less responsive to systemic antibiotics because of poor vascular perfusion in necrotic bone, large bone defects and persistent biofilm-based infection. Emerging bacterial resistance poses a major threat and new innovative treatment modalities are urgently needed to curb its current trajectory.

Materials and Methods

We present a new biphasic ceramic bone substitute consisting of hydroxyapatite and calcium sulphate for local antibiotic delivery in combination with bone regeneration. Gentamicin release was measured in four setups: 1) in vitro elution in Ringer’s solution; 2) local elution in patients treated for trochanteric hip fractures or uncemented hip revisions; 3) local elution in patients treated with a bone tumour resection; and 4) local elution in patients treated surgically for chronic corticomedullary osteomyelitis.


Bone & Joint Research
Vol. 6, Issue 5 | Pages 323 - 330
1 May 2017
Pijls BG Sanders IMJG Kuijper EJ Nelissen RGHH

Objectives

Infection of implants is a major problem in elective and trauma surgery. Heating is an effective way to reduce the bacterial load in food preparation, and studies on hyperthermia treatment for cancer have shown that it is possible to heat metal objects with pulsed electromagnetic fields selectively (PEMF), also known as induction heating. We therefore set out to answer the following research question: is non-contact induction heating of metallic implants effective in reducing bacterial load in vitro?

Methods

Titanium alloy cylinders (Ti6Al4V) were exposed to PEMF from an induction heater with maximum 2000 watts at 27 kHz after being contaminated with five different types of micro-organisms: Staphylococcus epidermidis; Staphylococcus aureus; Pseudomonas aeruginosa; spore-forming Bacillus cereus; and yeast Candida albicans. The cylinders were exposed to incremental target temperatures (35°C, 45°C, 50°C, 55°C, 60°C, 65°C, 70°C) for up to 3.5 minutes.


Bone & Joint Research
Vol. 6, Issue 5 | Pages 315 - 322
1 May 2017
Martinez-Perez M Perez-Jorge C Lozano D Portal-Nuñez S Perez-Tanoira R Conde A Arenas MA Hernandez-Lopez JM de Damborenea JJ Gomez-Barrena E Esbrit P Esteban J

Objectives

Implant-related infection is one of the most devastating complications in orthopaedic surgery. Many surface and/or material modifications have been developed in order to minimise this problem; however, most of the in vitro studies did not evaluate bacterial adhesion in the presence of eukaryotic cells, as stated by the ‘race for the surface’ theory. Moreover, the adherence of numerous clinical strains with different initial concentrations has not been studied.

Methods

We describe a method for the study of bacterial adherence in the presence of preosteoblastic cells. For this purpose we mixed different concentrations of bacterial cells from collection and clinical strains of staphylococci isolated from implant-related infections with preosteoblastic cells, and analysed the minimal concentration of bacteria able to colonise the surface of the material with image analysis.


Bone & Joint Research
Vol. 2, Issue 3 | Pages 58 - 65
1 Mar 2013
Johnson R Jameson SS Sanders RD Sargant NJ Muller SD Meek RMD Reed MR

Objectives

To review the current best surgical practice and detail a multi-disciplinary approach that could further reduce joint replacement infection.

Methods

Review of relevant literature indexed in PubMed.