Aims. The aim of this study was to determine the consensus best practice approach for the investigation and management of children (aged 0 to 15 years) in the UK with musculoskeletal infection (including septic arthritis, osteomyelitis, pyomyositis, tenosynovitis, fasciitis, and discitis). This consensus can then be used to ensure consistent, safe care for children in UK hospitals and those elsewhere with similar healthcare systems. Methods. A Delphi approach was used to determine consensus in three core aspects of care: 1) assessment, investigation, and diagnosis; 2) treatment; and 3) service, pathways, and networks. A steering group of paediatric orthopaedic surgeons created statements which were then evaluated through a two-round Delphi survey sent to all members of the British Society for Children’s Orthopaedic Surgery (BSCOS). Statements were only included (‘consensus in’) in the final agreed consensus if at least 75% of respondents scored the statement as critical for inclusion. Statements were discarded (‘consensus out’) if at least 75% of respondents scored them as not important for inclusion. Reporting these results followed the Appraisal Guidelines for Research and Evaluation. Results. A total of 133 children’s orthopaedic surgeons completed the first survey, and 109 the second. Out of 43 proposed statements included in the initial Delphi, 32 reached ‘consensus in’, 0 ‘consensus out’, and 11 ‘no consensus’. These 11 statements were then reworded, amalgamated, or deleted before the second Delphi round of eight statements. All eight were accepted as ‘consensus in’, resulting in a total of 40 approved statements. Conclusion. In the many aspects of medicine where relevant evidence is not available for clinicians to base their practice, a Delphi consensus can provide a strong body of opinion that acts as a benchmark for good quality clinical care. We would recommend clinicians managing children with musculoskeletal infection follow the guidance in the consensus statements in this article, to ensure care in all medical settings is consistent and safe. Cite this article: Bone Joint J 2023;105-B(7):815–820

We examined the usefulness of neutrophil CD64 expression in detecting local musculoskeletal infection and the impact of antibiotics on its expression. Of 141 patients suspected of musculoskeletal infection, 46 were confirmed by microbiological culture to be infected and 95 had infection excluded. The median CD64 count of patients with localised infection was 2230 molecules per cell (interquartile range (IQR) 918 to 4592) and that of the patients without infection was 937 molecules per cell (IQR 648 to 1309) (p < 0.001). The level of CD64 correlated with the CRP level in patients with infection, but not in those without infection (r = 0.59, p < 0.01). Receiver operator characteristic curve analysis revealed that CD64 was a good predictor of local infection. When the patients were subdivided into two groups based on the administration of antibiotics at the time of CD64 sampling, the sensitivity for detecting infection was better in those who had not received antibiotics. These results suggest that measurement of CD64 expression is a useful marker for local musculoskeletal infection

Aims. The aim of this paper was to present the clinical features of patients with musculoskeletal sources of methicillin-sensitive Staphylococcus aureus (MSSA) septicaemia. Patients and Methods. A total of 137 patients presented with MSSA septicaemia between 2012 and 2015. The primary source of infection was musculoskeletal in 48 patients (35%). Musculoskeletal infection was considered the primary source of septicaemia when endocarditis and other obvious sources were excluded. All patients with an arthroplasty at the time were evaluated for any prosthetic involvement. . Results. The most common site of infection was the spine, which occurred in 28 patients (58%), and was associated with abscess formation in 16. Back pain was the presenting symptom in these patients, with a positive predictive value of 100%. A total of 24 patients had a total of 42 arthroplasties of the hip or knee in situ. Prosthetic joint infection occurred in six of these patients (25%). In five patients, the infection originated outside the musculoskeletal system. Three patients (6%) with MSSA septicaemia from a musculoskeletal sources died. . Conclusion. Amongst the musculoskeletal sources of MSSA septicaemia, the spine was the most commonly involved. We recommend an MRI scan of the whole spine and pelvis in patients with MSSA septicaemia with back pain, when the primary source of infection has not been identified or clinical examination is unreliable. Cite this article: Bone Joint J 2017;99-B:1545–51

We compared the use of broth culture medium for samples taken in theatre with the standard practice of placing tissue samples in universal containers. A total of 67 consecutive patients had standard multiple samples of deep tissue harvested at surgery and distributed equally in theatre either to standard universal containers or to broth culture medium. These samples were cultured by direct and enrichment methods. The addition of broth in theatre to standard practice led to an increase in sensitivity from 83% to 95% and an increase in negative predictive value from 77% to 91%. Placing tissue samples directly into broth in the operating theatre is a simple, inexpensive way to increase the sensitivity of cultures from infected patients, and does not appear to compromise the specificity of these cultures.

Cite this article: Bone Joint J 2014;96-B:1566–70.

Aims. Total femoral arthroplasty (TFA) is a rare procedure used in cases of significant femoral bone loss, commonly from cancer, infection, and trauma. Low patient numbers have resulted in limited published work on long-term outcomes, and even less regarding TFA undertaken for non-oncological indications. The aim of this study was to evaluate the long-term clinical outcomes of all TFAs in our unit. Methods. Data were collected retrospectively from a large tertiary referral revision arthroplasty unit’s database. Inclusion criteria included all patients who underwent TFA in our unit. Preoperative demographics, operative factors, and short- and long-term outcomes were collected for analysis. Outcome was defined using the Musculoskeletal Infection Society (MSIS) outcome reporting tool. Results. Overall, 38 TFAs were identified. The mean age was 73 years (42 to 80). All patients underwent TFA for non-oncological indications, most commonly as a consequence of infection (53%) and periprosthetic fracture (26%). The mean follow-up time was ten years (0 to 26); 63% of TFAs were considered a success based upon the MSIS outcome reporting tool. The mean time between TFA and death was 8.5 years (0.2 to 19.2), with two patients dying within one year of surgery. Within the cohort, 66% suffered at least one complication, dislocation being most common (37%); 55% of the total cohort required at least one subsequent operation. In total, 70% of TFAs undertaken for infection were considered infection-free at time of final follow-up. The percentage of mobile patients improved from 52% to 65% between pre- and postoperation, with all patients being able to at least transfer from bed to chair at time of final review. Conclusion. This study is the largest in the UK assessing the use of TFA in patients with bone loss secondary to non-oncological conditions. It demonstrates that TFA has a significant complication profile, however it is favourable in terms of mortality and rehabilitation when compared to amputation and disarticulation. Cite this article: Bone Joint J 2023;105-B(8):888–894

Aims. The duration of systemic antibiotic treatment following first-stage revision surgery for periprosthetic joint infection (PJI) after total hip arthroplasty (THA) is contentious. Our philosophy is to perform an aggressive debridement, and to use a high local concentration of targeted antibiotics in cement beads and systemic prophylactic antibiotics alone. The aim of this study was to assess the success of this philosophy in the management of PJI of the hip using our two-stage protocol. Methods. The study involved a retrospective review of our prospectively collected database from which we identified all patients who underwent an intended two-stage revision for PJI of the hip. All patients had a diagnosis of PJI according to the major criteria of the Musculoskeletal Infection Society (MSIS) 2013, a minimum five-year follow-up, and were assessed using the MSIS working group outcome-reporting tool. The outcomes were grouped into ‘successful’ or ‘unsuccessful’. Results. A total of 299 two-stage revision THAs in 289 patients met the inclusion criteria, of whom 258 (86%) proceeded to second-stage surgery. Their mean age was 68.1 years (28 to 92). The median follow-up was 10.7 years (interquartile range (IQR) 6.3 to 15.0). A 91% success rate was seen in those patients who underwent reimplantation, decreasing to 86% when including those who did not proceed to reimplantation. The median duration of postoperative systemic antibiotics following the first stage was five days (IQR 5 to 9). There was no significant difference in outcome between those patients who were treated with antibiotics for ≤ 48 hours (p = 0.961) or ≤ five days (p = 0.376) compared with those who were treated with longer courses. Greater success rates were seen for Gram-positive PJIs (87%) than for Gram-negative (84%) and mixed-Gram PJIs (72%; p = 0.098). Conclusion. Aggressive surgical debridement with a high local concentration of targeted antibiotics at the time of first-stage revision surgery for PJI of the hip, without prolonged systemic antibiotics, provides a high rate of success, responsible antibiotic stewardship, and reduced hospital costs. Cite this article: Bone Joint J 2023;105-B(5):511–517

Aims. The outcome of repeat septic revision after a failed one-stage exchange for periprosthetic joint infection (PJI) in total knee arthroplasty (TKA) remains unknown. The aim of this study was to report the infection-free and all-cause revision-free survival of repeat septic revision after a failed one-stage exchange, and to determine whether the Musculoskeletal Infection Society (MSIS) stage is associated with subsequent infection-related failure. Methods. We retrospectively reviewed all repeat septic revision TKAs which were undertaken after a failed one-stage exchange between 2004 and 2017. A total of 33 repeat septic revisions (29 one-stage and four two-stage) met the inclusion criteria. The mean follow-up from repeat septic revision was 68.2 months (8.0 months to 16.1 years). The proportion of patients who had a subsequent infection-related failure and all-cause revision was reported and Kaplan-Meier survival for these endpoints was determined. Patients were categorized according to the MSIS staging system, and the association with subsequent infection was analyzed. Results. At the most recent follow-up, 17 repeat septic revisions (52%) had a subsequent infection-related failure and the five-year infection-free survival was 59% (95% confidence interval (CI) 39 to 74). A total of 19 underwent a subsequent all-cause revision (58%) and the five-year all-cause revision-free survival was 47% (95% CI 28 to 64). The most common indication for the first subsequent aseptic revision was loosening. The MSIS stage of the host status (p = 0.663) and limb status (p = 1.000) were not significantly associated with subsequent infection-related failure. Conclusion. Repeat septic revision after a failed one-stage exchange TKA for PJI is associated with a high rate of subsequent infection-related failure and all-cause revision. Patients should be counselled appropriately to manage expectations. The host and limb status according to the MSIS staging system were not associated with subsequent infection-related failure. Cite this article: Bone Joint J 2022;104-B(3):386–393

Aims. One-stage exchange for periprosthetic joint infection (PJI) in total hip arthroplasty (THA) is gaining popularity. The outcome for a repeat one-stage revision THA after a failed one-stage exchange for infection remains unknown. The aim of this study was to report the infection-free and all-cause revision-free survival of repeat one-stage exchange, and to investigate the association between the Musculoskeletal Infection Society (MSIS) staging system and further infection-related failure. Methods. We retrospectively reviewed all repeat one-stage revision THAs performed after failed one-stage exchange THA for infection between January 2008 and December 2016. The final cohort included 32 patients. The mean follow-up after repeat one-stage exchange was 5.3 years (1.2 to 13.0). The patients with a further infection-related failure and/or all-cause revision were reported, and Kaplan-Meier survival for these endpoints determined. Patients were categorized according to the MSIS system, and its association with further infection was analyzed. Results. A total of eight repeat septic revisions (25%) developed a further infection-related failure, and the five-year infection-free survival was 81% (95% confidence interval (CI) 57 to 92). Nine (28%) underwent a further all-cause revision and the five-year all-cause revision-free survival was 74% (95% CI 52 to 88). Neither the MSIS classification of the host status (p = 0.423) nor the limb status (p = 0.366) was significantly associated with further infection-related failure. Conclusion. Repeat one-stage exchange for PJI in THA is associated with a favourable five-year infection-free and all-cause revision-free survival. Notably, the rate of infection control is encouraging when compared with the reported rates after repeat two-stage exchange. The results can be used to counsel patients and help clinicians make informed decisions about treatment. With the available number of patients, further infection-related failure was not associated with the MSIS host or limb status. Cite this article: Bone Joint J 2022;104-B(1):27–33

Aims. The preoperative diagnosis of periprosthetic joint infection (PJI) remains a challenge due to a lack of biomarkers that are both sensitive and specific. We investigated the performance characteristics of polymerase chain reaction (PCR), interleukin-6 (IL6), and calprotectin of synovial fluid in the diagnosis of PJI. Methods. We performed systematic search of PubMed, Embase, The Cochrane Library, Web of Science, and Science Direct from the date of inception of each database through to 31 May 2021. Studies which described the diagnostic accuracy of synovial fluid PCR, IL6, and calprotectin using the Musculoskeletal Infection Society criteria as the reference standard were identified. Results. Overall, 31 studies were identified: 20 described PCR, six described IL6, and five calprotectin. The sensitivity and specificity were 0.78 (95% confidence interval (CI) 0.67 to 0.86) and 0.97 (95% CI 0.94 to 0.99), respectively, for synovial PCR;, 0.86 (95% CI 0.74 to 0.92), and 0.94 (95% CI 0.90 to 0.96), respectively, for synovial IL6; and 0.94 (95% CI 0.82 to 0.98) and 0.93 (95% CI 0.85 to 0.97), respectively, for synovial calprotectin. Likelihood ratio scattergram analyses recommended clinical utility of synovial fluid PCR and IL6 as a confirmatory test only. Synovial calprotectin had utility in the exclusion and confirmation of PJI. Conclusion. Synovial fluid PCR and IL6 had low sensitivity and high specificity in the diagnosis of PJI, and is recommended to be used as confirmatory test. In contrast, synovial fluid calprotectin had both high sensitivity and specificity with utility in both the exclusion and confirmation of PJI. We recommend use of synovial fluid calprotectin studies in the preoperative workup of PJI. Cite this article: Bone Joint J 2022;104-B(3):311–320

Aims. As a proven and comprehensive molecular technique, metagenomic next-generation sequencing (mNGS) has shown its potential in the diagnosis of pathogens in patients with periprosthetic joint infection (PJI), using a single type of specimen. However, the optimal use of mNGS in the management of PJI has not been explored. In this study, we evaluated the diagnostic value of mNGS using three types of specimen with the aim of achieving a better choice of specimen for mNGS in these patients. Methods. In this prospective study, 177 specimens were collected from 59 revision arthroplasties, including periprosthetic tissues, synovial fluid, and prosthetic sonicate fluid. Each specimen was divided into two, one for mNGS and one for culture. The criteria of the Musculoskeletal Infection Society were used to define PJI (40 cases) and aseptic failure (19 cases). Results. The sensitivity and specificity of mNGS in the diagnosis of PJI were 95% and 94.7%, respectively, for all types of specimen. The sensitivity and specificity were 65% and 100%, respectively, for periprosthetic tissues, 87.5% and 94.7%, respectively, for synovial fluid, and 92.5% and 94.7%, respectively, for prosthetic sonicate fluid. The mNGS of prosthetic sonicate fluid outperformed that for other types of specimen in the rates of detection of pathogens (84.6%), sequencing reads (> ten-fold) and the rate of genome coverage (> five-fold). Conclusion. mNGS could serve as an accurate diagnostic tool in the detection of pathogens in patients with a PJI using three types of specimen. Due to its superior perfomance in identifying a pathogen, mNGS of prosthetic sonicate fluid provides the most value and may partly replace traditional tests such as bacteriological culture in these patients. Cite this article: Bone Joint J 2021;103-B(5):923–930

Aims. Debridement, antibiotics, and implant retention (DAIR) remains one option for the treatment of acute periprosthetic joint infection (PJI) despite imperfect success rates. Intraosseous (IO) administration of vancomycin results in significantly increased local bone and tissue concentrations compared to systemic antibiotics alone. The purpose of this study was to evaluate if the addition of a single dose of IO regional antibiotics to our protocol at the time of DAIR would improve outcomes. Methods. A retrospective case series of 35 PJI TKA patients, with a median age of 67 years (interquartile range (IQR) 61 to 75), who underwent DAIR combined with IO vancomycin (500 mg), was performed with minimum 12 months' follow-up. A total of 26 patients with primary implants were treated for acute perioperative or acute haematogenous infections. Additionally, nine patients were treated for chronic infections with components that were considered unresectable. Primary outcome was defined by no reoperations for infection, nor clinical signs or symptoms of PJI. Results. Mean follow-up for acute infection was 16.5 months (12.1 to 24.2) and 15.8 months (12 to 24.8) for chronic infections with unresectable components. Overall non-recurrence rates for acute infection was 92.3% (24/26) but only 44.4% (4/9) for chronic infections with unresectable components. The majority of patients remained on suppressive oral antibiotics. Musculoskeletal Infection Society (MSIS) host grade was a significant indicator of failure (p < 0.001). Conclusion. The addition of IO vancomycin at the time of DAIR was shown to be safe with improved results compared to current literature using standard DAIR without IO antibiotic administration. Use of this technique in chronic infections should be applied with caution. While these results are encouraging, this technique requires longer follow-up before widespread adoption. Cite this article: Bone Joint J 2021;103-B(6 Supple A):185–190

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. Results. Using the MSIS criteria to diagnose PJI as the reference standard, the sensitivity and specificity of NGS were 60.9% and 89.9%, respectively, while culture resulted in sensitivity of 76.9% and specificity of 95.3%. PCR had a low sensitivity of 18.4%. There was no significant difference based on sample collection method (tissue swab or synovial fluid) (p = 0.760). There were 11 samples that were culture-positive and NGS-negative, of which eight met MSIS criteria for diagnosing infection. Conclusion. In our series, NGS did not provide superior sensitivity or specificity results compared to culture. PCR has little utility as a standalone test for PJI diagnosis with a sensitivity of only 18.4%. Currently, several laboratory tests for PJI diagnosis should be obtained along with the overall clinical picture to help guide decision-making for PJI treatment. Cite this article: Bone Joint J 2021;103-B(1):26–31

Aims. The diagnosis of periprosthetic joint infection (PJI) can be difficult. All current diagnostic tests have problems with accuracy and interpretation of results. Many new tests have been proposed, but there is no consensus on the place of many of these in the diagnostic pathway. Previous attempts to develop a definition of PJI have not been universally accepted and there remains no reference standard definition. Methods. This paper reports the outcome of a project developed by the European Bone and Joint Infection Society (EBJIS), and supported by the Musculoskeletal Infection Society (MSIS) and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Implant-Associated Infections (ESGIAI). It comprised a comprehensive review of the literature, open discussion with Society members and conference delegates, and an expert panel assessment of the results to produce the final guidance. Results. This process evolved a three-level approach to the diagnostic continuum, resulting in a definition set and guidance, which has been fully endorsed by EBJIS, MSIS, and ESGIAI. Conclusion. The definition presents a novel three-level approach to diagnosis, based on the most robust evidence, which will be useful to clinicians in daily practice. Cite this article: Bone Joint J 2021;103-B(1):18–25

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

Aims. There is a paucity of long-term studies analyzing risk factors for failure after single-stage revision for periprosthetic joint infection (PJI) following total hip arthroplasty (THA). We report the mid- to long-term septic and non-septic failure rate of single-stage revision for PJI after THA. Methods. We retrospectively reviewed 88 cases which met the Musculoskeletal Infection Society (MSIS) criteria for PJI. Mean follow-up was seven years (1 to 14). Septic failure was diagnosed with a Delphi-based consensus definition. Any reoperation for mechanical causes in the absence of evidence of infection was considered as non-septic failure. A competing risk regression model was used to evaluate factors associated with septic and non-septic failures. A Kaplan-Meier estimate was used to analyze mortality. Results. The cumulative incidence of septic failure was 8% (95% confidence interval (CI) 3.5 to 15) at one year, 13.8% (95% CI 7.6 to 22) at two years, and 19.7% (95% CI 12 to 28.6) at five and ten years of follow-up. A femoral bone defect worse than Paprosky IIIA (hazard ratio (HR) 13.58 (95% CI 4.86 to 37.93); p < 0.001) and obesity (BMI ≥ 30 kg/m. 2. ; HR 3.88 (95% CI 1.49 to 10.09); p = 0.005) were significantly associated with septic failure. Instability and periprosthetic fracture were the most common reasons for mechanical failure (5.7% and 4.5%, respectively). The cumulative incidence of aseptic failure was 2% (95% CI 0.4 to 7) at two years, 9% (95% CI 4 to 17) at five years, and 12% (95% CI 5 to 22) at ten years. A previous revision to treat PJI was significantly associated with non-septic failure (HR 9.93 (95% CI 1.77 to 55.46); p = 0.009). At the five-year timepoint, 93% of the patients were alive (95% CI 84% to 96%), which fell to 86% (95% CI 75% to 92%) at ten-year follow-up. Conclusion. Massive femoral bone loss was associated with greater chances of developing a further septic failure. All septic failures occurred within the first five years following the one-stage exchange. Surgeons should be aware of instability and periprosthetic fracture being potential causes of further aseptic revision surgery. Cite this article: Bone Joint J 2021;103-B(7):1247–1253

Aims. It remains difficult to diagnose early postoperative periprosthetic joint infection (PJI) following total knee arthroplasty (TKA). We aimed to validate the optimal cutoff values of ESR, CRP, and synovial fluid analysis for detecting early postoperative PJI in a large series of primary TKAs. Methods. We retrospectively identified 27,066 primary TKAs performed between 2000 and 2019. Within 12 weeks, 169 patients (170 TKAs) had an aspiration. The patients were divided into two groups: those evaluated ≤ six weeks, or between six and 12 weeks postoperatively. The 2011 Musculoskeletal Infection Society (MSIS) criteria for PJI diagnosis in 22 TKAs. The mean follow-up was five years (two months to 17 years). The results were compared using medians and Mann-Whitney U tests and thresholds were analyzed using receiver operator characteristic curves. Results. Within six weeks, the median CRP (101 mg/l vs 35 mg/l; p = 0.011), synovial WBCs (58,295 cells/μl vs 2,121 cells/μl; p ≤ 0.001), percentage of synovial neutrophils (91% vs 71% (p < 0.001), and absolute synovial neutrophil count (ANC) (50,748 cells/μl vs 1,386 cells/μl (p < 0.001) were significantly higher in infected TKAs. Between six and 12 weeks, the median CRP (85 mg/l vs 5 mg/l (p < 0.001)), ESR (33 mm/hr vs 14 mm/hr (p = 0.015)), synovial WBCs (62,247 cells/μl vs 620 cells/μl (p < 0.001)), percentage of synovial neutrophils (93% vs 54% (p < 0.001)), and ANC (55,911 cells/μl vs 326 cells/μl (p < 0.001)) were also significantly higher in infected TKAs. Optimal thresholds at ≤ six weeks were: CRP ≥ 82 mg/l (sensitivity 70%, specificity 77%), synovial WBCs ≥ 8,676 cells/μl (83%, 90%), percentage of synovial neutrophils ≥ 88% (67%, 78%), and ANC ≥ 8,346 cells/μl (83%, 91%). Between six and 12 weeks, thresholds were: CRP ≥ 34 mg/l (90%, 93%), synovial WBCs ≥ 1,983 cells/μl (80%, 85%), percentage of synovial neutrophils ≥ 76% (80%, 81%), and ANC ≥ 1,684 cells/μl (80%, 87%). Conclusion. Early PJI after TKA should be suspected within six weeks if the CRP is ≥ 82 mg/l, synovial WBCs are ≥ 8,676 cells/μl, the percentage of synovial neutrophils is ≥ 88%, and/or the ANC is ≥ 8,346 cells/μl. Between six and 12 weeks, thresholds include a CRP of ≥ 34 mg/l, synovial WBC of ≥ 1,983 cells/μl, a percentage of synovial neutrophils of ≥ 76%, and/or an ANC of ≥ 1,684 cells/μl. Cite this article: Bone Joint J 2021;103-B(6 Supple A):177–184

Aims. We aimed to report the mid- to long-term rates of septic and aseptic failure after two-stage revision surgery for periprosthetic joint infection (PJI) following total hip arthroplasty (THA). Methods. We retrospectively reviewed 96 cases which met the Musculoskeletal Infection Society criteria for PJI. The mean follow-up was 90 months (SD 32). Septic failure was assessed using a Delphi-based consensus definition. Any further surgery undertaken for aseptic mechanical causes was considered as aseptic failure. The cumulative incidence with competing risk analysis was used to predict the risk of septic failure. A regression model was used to evaluate factors associated with septic failure. The cumulative incidence of aseptic failure was also analyzed. Results. There were 23 septic failures at final follow-up, with a cumulative incidence of 14% (95% confidence interval (CI) 8% to 22%) at one year, 18% (95% CI 11% to 27%) at two years, 22% (95% CI 14% to 31%) at five years, and 23% (95% CI 15% to 33%) at ten years. Having at least one positive culture (hazard ratio (HR) 2.38 (interquartile range (IQR) 1.19 to 4.74); p = 0.013), or a positive intraoperative frozen section (HR 2.55 (IQR 1.06 to 6.15); p = 0.037) was significantly associated with septic failure after reimplantation. With dislocation being the most common cause of aseptic revision (5.2%), the cumulative incidence of aseptic failure was 1% (95% CI 0% to 5%) at one year, 6% (95% CI 1% to 8%) at five years, and 8% (95%CI 3% to 17%) at ten years. Conclusion. If there is no recurrent infection in the five years following reimplantation, the chances of further infection thereafter are remote. While the results of a frozen section may be a reliable guide to the timing of reimplantation, intraoperative culture has, currently, only prognostic value. Surgeons should be aware that instability remains a potential indication for further revision surgery. Cite this article: Bone Joint J 2021;103-B(1):79–86

Aims. To establish the utility of adding the laboratory-based synovial alpha-defensin immunoassay to the traditional diagnostic work-up of a prosthetic joint infection (PJI). Methods. A group of four physicians evaluated 158 consecutive patients who were worked up for PJI, of which 94 underwent revision arthroplasty. Each physician reviewed the diagnostic data and decided on the presence of PJI according to the 2014 Musculoskeletal Infection Society (MSIS) criteria (yes, no, or undetermined). Their initial randomized review of the available data before or after surgery was blinded to each alpha-defensin result and a subsequent randomized review was conducted with each result. Multilevel logistic regression analysis assessed the effect of having the alpha-defensin result on the ability to diagnose PJI. Alpha-defensin was correlated to the number of synovial white blood cells (WBCs) and percentage of polymorphonuclear cells (%PMN). Results. Intraobserver reliability and interobserver agreement did not change when the alpha-defensin result was available. Positive alpha-defensin results had greater synovial WBCs (mean 31,854 cells/μL, SD 32,594) and %PMN (mean 93.0%, SD 5.5%) than negative alpha-defensin results (mean 974 cells/μL, SD 3,988; p < 0.001 and mean 39.4% SD 28.6%; p < 0.001). Adding the alpha-defensin result did not alter the diagnosis of a PJI using preoperative (odds ratio (OR) 0.52, 95% confidence interval (CI) 0.14 to 1.88; p = 0.315) or operative (OR 0.52, CI 0.18 to 1.55; p = 0.242) data when clinicians already decided that PJI was present or absent with traditionally available testing. However, when undetermined with traditional preoperative testing, alpha-defensin helped diagnose (OR 0.44, CI 0.30 to 0.64; p < 0.001) or rule out (OR 0.41, CI 0.17 to 0.98; p = 0.044) PJI. Of the 27 undecided cases with traditional testing, 24 (89%) benefited from the addition of alpha-defensin testing. Conclusion. The laboratory-based synovial alpha-defensin immunoassay did not help diagnose or rule out a PJI when added to routine serologies and synovial fluid analyses except in cases where the diagnosis of PJI was unclear. We recommend against the routine use of alpha-defensin and suggest using it only when traditional testing is indeterminate. Cite this article: Bone Joint J 2020;102-B(5):593–599

Aims. Prosthetic joint infection (PJI) remains a major clinical challenge. Neutrophil CD64 index, Fc-gamma receptor 1 (FcγR1), plays an important role in mediating inflammation of bacterial infections and therefore could be a valuable biomarker for PJI. The aim of this study is to compare the neutrophil CD64 index in synovial and blood diagnostic ability with the standard clinical tests for discrimination PJI and aseptic implant failure. Methods. A total of 50 patients undergoing revision hip and knee arthroplasty were enrolled into a prospective study. According to Musculoskeletal Infection Society (MSIS) criteria, 25 patients were classified as infected and 25 as not infected. In all patients, neutrophil CD64 index and percentage of polymorphonuclear neutrophils (PMN%) in synovial fluid, serum CRP, ESR, and serum CD64 index levels were measured preoperatively. Receiver operating characteristic (ROC) curves and the area under the curve (AUC) were analyzed for each biomarker. Results. Serum CD64 index showed no significant difference between the two groups (p = 0.091). Synovial fluid CD64 index and PMN% discriminated good differentiation between groups of PJI and aseptic failure with AUC of 0.946 (95% confidence interval (CI) 0.842 to 0.990) and 0.938 (95% CI 0.832 to 0.987) separately. The optimal threshold value of synovial CD64 index for the diagnosis of PJI was 0.85, with a sensitivity of 92.00%, a specificity of 96.00%, and diagnostic odds ratio (DOR) of 227.11. Conclusion. The present study demonstrates that CD64 index in synovial fluid could be a promising laboratory marker for screening PJI. The cut-off values of 0.85 for synovial CD64 index has the potential to distinguish aseptic failure from PJI. Cite this article: Bone Joint J 2020;102-B(4):463–469

Aims. Two-stage exchange arthroplasty is the most common definitive treatment for prosthetic joint infection (PJI) in the USA. Complications that occur during treatment are often not considered. The purpose of this study was to analyze complications in patients undergoing two-stage exchange for infected total knee arthroplasty (TKA) and determine when they occur. Methods. We analyzed all patients that underwent two-stage exchange arthroplasty for treatment of PJI of the knee from January 2010 to December 2018 at a single institution. We categorized complications as medical versus surgical. The intervals for complications were divided into: interstage; early post-reimplantation (three months); and late post-reimplantation (three months to minimum one year). Minimum follow-up was one year. In total, 134 patients underwent a first stage of a two-stage exchange. There were 69 males and 65 females with an mean age at first stage surgery of 67 years (37 to 89). Success was based on the new Musculoskeletal Infection Society (MSIS) definition of success reporting. Results. Overall, 70 (52%) patients experienced a complication during the planned two-stage treatment, 36 patients (27%) experienced a medical complication and 47 (41%) patients experienced a surgical complication. There was an 18% mortality rate (24/134) at a mean of 3.7 years (0.09 to 8.3). During the inter-stage period, 28% (37/134) of patients experienced a total of 50 complications at a median of 47 days (interquartile range (IQR) 18 to 139). Of these 50 complications, 22 were medical and 28 required surgery. During this inter-stage period, four patients died (3%) and an additional five patients (4%) failed to progress to the second stage. While 93% of patients (125/134) were reimplanted, only 56% (77/134) of the patients were successfully treated without antibiotic suppression (36%, 28/77) or with antibiotic suppression (19%, 15/77) at one year. Conclusion. Reported rates of success of two stage exchanges for PJI have not traditionally considered complications in the definition of success. In our series, significant numbers of patients experienced complications, more often after reimplantation, highlighting the morbidity of this method of treatment. Cite this article: Bone Joint J 2020;102-B(6 Supple A):145–150

Aims. Failure of irrigation and debridement (I&D) for prosthetic joint infection (PJI) is influenced by numerous host, surgical, and pathogen-related factors. We aimed to develop and validate a practical, easy-to-use tool based on machine learning that may accurately predict outcome following I&D surgery taking into account the influence of numerous factors. Methods. This was an international, multicentre retrospective study of 1,174 revision total hip (THA) and knee arthroplasties (TKA) undergoing I&D for PJI between January 2005 and December 2017. PJI was defined using the Musculoskeletal Infection Society (MSIS) criteria. A total of 52 variables including demographics, comorbidities, and clinical and laboratory findings were evaluated using random forest machine learning analysis. The algorithm was then verified through cross-validation. Results. Of the 1,174 patients that were included in the study, 405 patients (34.5%) failed treatment. Using random forest analysis, an algorithm that provides the probability for failure for each specific patient was created. By order of importance, the ten most important variables associated with failure of I&D were serum CRP levels, positive blood cultures, indication for index arthroplasty other than osteoarthritis, not exchanging the modular components, use of immunosuppressive medication, late acute (haematogenous) infections, methicillin-resistant Staphylococcus aureus infection, overlying skin infection, polymicrobial infection, and older age. The algorithm had good discriminatory capability (area under the curve = 0.74). Cross-validation showed similar probabilities comparing predicted and observed failures indicating high accuracy of the model. Conclusion. This is the first study in the orthopaedic literature to use machine learning as a tool for predicting outcomes following I&D surgery. The developed algorithm provides the medical profession with a tool that can be employed in clinical decision-making and improve patient care. Future studies should aid in further validating this tool on additional cohorts. Cite this article: Bone Joint J 2020;102-B(7 Supple B):11–19

Aims. Prosthetic joint infection (PJI) and aseptic loosening in total hip arthroplasty (THA) can present with pain and osteolysis. The Musculoskeletal Infection Society (MSIS) has provided criteria for the diagnosis of PJI. The aim of our study was to analyze the utility of F18-fluorodeoxyglucose (FDG) positron emission tomography (PET) CT scan in the preoperative diagnosis of septic loosening in THA, based on the current MSIS definition of prosthetic joint infection. Patients and Methods. A total of 130 painful unilateral cemented THAs with a mean follow-up of 5.17 years (. sd. 1.12) were included in this prospective study. The mean patient age was 67.5 years (. sd. 4.85). Preoperative evaluation with inflammatory markers, aspiration, and an F18 FDG PET scan were performed. Diagnostic utility tests were also performed, based on the MSIS criteria for PJI and three samples positive on culture alone. Results. The mean erythrocyte sedimentation rate, C-reactive protein, and white cell count were 47.83 mm/hr, 25.21 mg/l, and 11.05 × 10. 9. /l, respectively. The sensitivity, specificity, accuracy, negative predictive value, and false-positive rate of FDG PET compared with MSIS criteria were 94.87%, 38.46 %, 56.38%, 94.59 %, and 60.21%, respectively. The false-positive rate of FDG PET compared with culture alone was 77.4%. Conclusion. FDG PET has a definitive role in the preoperative evaluation of suspected PJI. This the first study to evaluate its utility based on MSIS criteria and compare it with microbiology results alone. However, FDG PET has a high false-positive rate. Therefore, we suggest that F18 FDG PET is useful in confirming the absence of infection, but if positive, may not be confirmatory of PJI. Cite this article: Bone Joint J 2019;101-B:910–914

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). Results. In total, 178 (113 THA, 65 TKA) were classified as infected. The biopsy procedure had a sensitivity of 93.8%, a specificity of 97.3%, a positive predictive value (PPV) of 94.9%, a negative predictive value (NPV) of 96.7%, and an accuracy of 96.1%. Of the 178 infected patients, 26 showed a difference in the detected bacteria from the biopsy and the revision surgery (14.6%). This difference required a change to antibiotic therapy in only two cases (1.1%). Conclusion. Biopsy is a useful tool to diagnose PJI, but there may be a difference in the detected bacteria between the biopsy and revision surgery. However, this did not affect the choice of antibiotic therapy in most cases, rendering the clinical relevance of this phenomenon as low. Cite this article: Bone Joint J 2020;102-B(3):329–335

Aims. In patients with a “dry” aspiration during the investigation of prosthetic joint infection (PJI), saline lavage is commonly used to obtain a sample for analysis. The aim of this study was to investigate prospectively the impact of saline lavage on synovial fluid analysis in revision arthroplasty. Methods. Patients undergoing revision hip (THA) or knee arthroplasty (TKA) for any septic or aseptic indication were enrolled. Intraoperatively, prior to arthrotomy, the maximum amount of fluid possible was aspirated to simulate a dry tap (pre-lavage) followed by the injection with 20 ml of normal saline and re-aspiration (post-lavage). Pre- and post-lavage synovial white blood cell (WBC) count, percent polymorphonuclear cells (%PMN), and cultures were compared. Results. A total of 78 patients had data available for analysis; 17 underwent revision THA and 61 underwent revision TKA. A total of 16 patients met modified Musculoskeletal Infection Society (MSIS) criteria for PJI. Pre- and post-lavage %PMNs were similar in septic patients (87% vs 85%) and aseptic patients (35% vs 39%). Pre- and post-lavage synovial fluid WBC count were far more disparate in septic (53,553 vs 8,275 WBCs) and aseptic (1,103 vs 268 WBCs) cohorts. At a cutoff of 80% PMN, the post-lavage aspirate had a sensitivity of 75% and specificity of 95%. At a cutoff of 3,000 WBCs, the post-lavage aspirate had a sensitivity of 63% and specificity of 98%. As the post-lavage synovial WBC count increased, the difference between pre- and post-lavage %PMN decreased (mean difference of 5% PMN in WBC < 3,000 vs mean difference 2% PMN in WBC > 3,000, p = 0.013). Of ten positive pre-lavage fluid cultures, only six remained positive post-lavage. Conclusion. While saline lavage aspiration significantly lowered the synovial WBC count, the %PMN remained similar, particularly at WBC counts of > 3,000. These findings suggest that in patients with a dry-tap, the %PMN of a saline lavage aspiration has reasonable sensitivity (75%) for the detection of PJI. Cite this article: Bone Joint J 2020;102-B(6 Supple A):138–144

Aims. Fungal prosthetic joint infections (PJIs) are rare and account for about 1% of total PJIs. Our aim was to present clinical and microbiological results in treating these patients with a two-stage approach and antifungal spacers. Patients and Methods. We retrospectively reviewed our institutional database and identified 26 patients with positive fungal cultures and positive Musculoskeletal Infection Society (MSIS) criteria for PJI who were treated between 2009 and 2017. We identified 18 patients with total hip arthroplasty (THA) and eight patients with total knee arthroplasty (TKA). The surgical and antifungal treatment, clinical and demographic patient data, complications, relapses, and survival were recorded and analyzed. Results. The median follow-up was 33 months. The success rate was 38.5% (10/26). Fluconazole resistance was found in 15%. Bacterial co-infection was common in 44% of patients for THA and 66% of patients with TKA. Mortality, reoperations, and treatment failure were common complications. Conclusion. Treatment with a two-stage exchange is a possible option for treatment, although fungal infections have a high failure rate. Therapeutic factors for treatment success remain unclear. Cite this article: Bone Joint J 2019;101-B:589–595

Aims. Recurrent infection following two-stage revision total hip arthroplasty (THA) for prosthetic joint infection (PJI) is a devastating complication. The purpose of this study was to report the survival of repeat two-stage revision hip arthroplasty, describe complications, and identify risk factors for failure. Patients and Methods. We retrospectively identified 19 hips (19 patients) that had undergone repeat two-stage revision THA for infection between 2000 to 2013. There were seven female patients (37%) and the mean age was 60 years (30 to 85). Survival free from revision was assessed via Kaplan–Meier analysis. The patients were classified according to the Musculoskeletal Infection Society (MSIS) system, and risk factors for failure were identified. Mean follow-up was four years (2 to 11). Results. Gram-positive bacteria were responsible for 16/17 (94%) of the re-infections where microbes were identified. Following the repeat two-stage exchange arthroplasty, survival free from any revision was 74% (95% confidence interval (CI) 56% to 96%, 14 at risk) at two years and 45% (95% CI 25% to 75%, five at risk) at five years. Failure to control infection resulted in re-operation or revision in 42%A of patients (8/19). Survival free from revision was not dependent on host grade. Conclusion. Re-infection after two-stage exchange hip arthroplasty for PJI presents a challenging scenario. Repeat two-stage exchange arthroplasty has a low survival free from revision at five years (45%) and a high rate of re-infection (42%). Cite this article: Bone Joint J 2018;100-B:1157–61

Aims. The purpose of this current multicentre study is to analyse the presence of alpha-defensin proteins in synovial fluid using the Synovasure lateral flow device and to determine its diagnostic reliability and accuracy compared with the prosthetic joint infection (PJI) criteria produced by the Musculoskeletal Infection Society (MSIS). Patients and Methods. A cohort of 121 patients comprising 85 total knee arthroplasties and 36 total hip arthroplasties was prospectively evaluated between May 2015 and June 2016 in three different orthopaedic centres. The tests were performed on patients with a chronically painful prosthesis undergoing a joint aspiration in a diagnostic pathway or during revision surgery. Results. Based on the MSIS criteria, 34 patients (28%) would have had a PJI, and 87 patients had no PJI. Testing with the lateral flow device had a sensitivity of 97.1% (95% confidence intervals (CI) 84.5 to 99.9) and a specificity of 96.6% (95% CI 90.3 to 99.2). The positive predictive value was 91.7% (95% CI 77.7% to 98.3), and the negative predictive value was 98.8% (95% CI 93.6 to 99.9). Receiver operator characteristics analysis demonstrated an area under the curve for the Synovasure test of 0.97 (95% CI 0.93 to 1.00). Conclusion. Our findings suggest that the Synovasure test has an excellent diagnostic performance to confirm or reject the diagnosis of a PJI. The results are promising for the care of the painful or problematic knee and hip joint arthroplasty and the test should be considered as part of the diagnostic toolbox for PJIs. Cite this article: Bone Joint J 2017;99-B:1176–82

Aims. The aim of this study was to compare the results of 16S/28S rRNA sequencing with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and synovial fluid analysis in the diagnosis of prosthetic joint infection (PJI). Patients and Methods. Between September 2015 and August 2016, 214 consecutive patients were enrolled. In the study population, there were 25 patients with a PJI and 189 controls. Of the PJI patients, 14 (56%) were women, and the mean age at the time of diagnosis was 65 years (38 to 83). The ESR and CRP levels were measured, and synovial fluid specimens were collected prospectively. Synovial fluid was subjected to reverse transcription polymerase chain reaction (RT-PCR)/sequence analysis targeting the 16S/28S rRNA, and to conventional culture. Laboratory personnel who were blind to the clinical information performed all tests. The diagnosis of PJI was based on the criteria of the Musculoskeletal Infection Society. Results. A total of 25 patients had a confirmed PJI. In 20 cases of monomicrobial PJI, the PCR products could be perfectly matched with the 16S/28S rRNA genes specific for different species of bacteria provided by sequence analysis. Of the five polymicrobial cases of PJI, 16S/28S rRNA PCR sequence analysis failed to identify the concordant bacteria species. In the 189 control patients, there was one false-positive RT-PCR result. The sensitivity and specificity of the molecular diagnosis method were 100% (95% confidence interval (CI) 85.7 to 100) and 99.5% (95% CI 97.1 to 99.9), respectively, whereas the positive and negative predictive values of PCR were 96.1% (95% CI 79.6 to 99.9) and 100% (95% CI 98.1 to 100), respectively. The PCR results were significantly better than serological diagnostic methods (p = 0.004 and p = 0.010 for ESR and CRP, respectively), the synovial fluid white blood cell (WBC) count (p = 0.036), and percentage of polymorphonuclear cells (PMN%) (p = 0.014). Conclusion. Stepwise RT-PCR and sequence analysis of the 16S/28S rRNA carried out under stringent laboratory conditions achieved highly sensitive and specific results for the differentiation between aseptic and septic joints undergoing arthroplasty. Sequence analysis successfully identified bacterial strains in monomicrobial infections but failed to identify molecular targets in polymicrobial infections. Further refinement of the protocols to identify the bacteria in polymicrobial infections is needed. Cite this article: Bone Joint J 2018;100-B:1345–51

Aims. The results of irrigation and debridement with component retention (IDCR) in the treatment of acutely infected total knee arthroplasties (TKAs) have been variable. The aim of this study was to assess the outcome after IDCR when combined with chronic antibiotic suppression. We also evaluated survivorship free from subsequent infection, removal of the components, and death, as well as the risk factors for failure. Patients and Methods. This was a single-centre retrospective review of 134 infected primary TKAs that were treated with IDCR. Infections within four weeks of the procedure were defined as acute postoperative infections, and those occurring more than four weeks after the procedure with symptoms for less than three weeks were defined as acute haematogenous infections. Patients were treated with intravenous antibiotics for four to six weeks, followed by chronic oral antibiotic suppression. Estimates of survival were made using a competing risk analysis. The mean follow-up was five years (2.1 to 13). Results. The infection was an acute postoperative infection in 23 TKAs and an acute haematogenous infection in 111 TKAs. The incidence of subsequent infection was 36% in those with an acute postoperative infection and 33% in those with a haematogenous infection, five years postoperatively (p = 0.40). Age < 60 years increased the risk of subsequent infection (hazard ratio (HR) 2.4; p = 0.009) and removal of the components (HR 2.8; p = 0.007). Infection with a staphylococcal species increased the risk of subsequent infection (HR 3.6; p < 0.001), and removal of the components (HR 3.2; p = 0.002). Musculoskeletal Infection Society host type and local extremity grade, body mass index (BMI), the duration of symptoms, gender, and the presence of a monoblock tibial component had no significant effect on the outcome. Conclusion. In a rigorously defined group of acute periprosthetic infections after TKA treated with IDCR and chronic antibiotic suppression, the infection-free survival at five years was 66%. The greatest risk factor for failure was an infection with a staphylococcal species, followed by age of < 60 years. Cite this article: Bone Joint J 2018;100-B:1471–76

Aims. The diagnosis of periprosthetic joint infection (PJI) remains demanding due to limitations of all the available diagnostic tests. The synovial fluid marker, α-defensin, is a promising adjunct for the assessment of potential PJI. The purpose of this study was to investigate the qualitative assessment of α-defensin, using Synovasure to detect or exclude periprosthetic infection in total joint arthroplasty. Patients and Methods. We studied 50 patients (28 women, 22 men, mean age 65 years; 20 to 89) with a clinical indication for revision arthroplasty who met the inclusion criteria of this prospective diagnostic study. The presence of α-defensin was determined using the qualitative Synovasure test and compared with standard diagnostic methods for PJI. Based on modified Musculoskeletal Infection Society (MSIS) criteria, 13 cases were categorised as septic and 36 as aseptic revisions. One test was inconclusive. Results. The Synovasure test achieved a sensitivity of 69% and a specificity of 94%. The positive and negative likelihood ratios were 12.46 and 0.33, respectively. A good diagnostic accuracy for PJI, with an area under the curve of 0.82, was demonstrated. Adjusted p-values using the method of Hochberg showed that Synovasure is as good at diagnosing PJI as histology (p = 0.0042) and bacteriology with one positive culture (p = 0.0327). Conclusion. With its ease of use and rapid results after approximately ten minutes, Synovasure may be a useful adjunct in the diagnosis of PJI. Cite this article: Bone Joint J 2017;99-B:66–72

Aims . Recently, several synovial biomarkers have been introduced into the algorithm for the diagnosis of a prosthetic joint infection (PJI). Alpha defensin is a promising biomarker, with a high sensitivity and specificity, but it is expensive. Calprotectin is a protein that is present in the cytoplasm of neutrophils, is released upon neutrophil activation and exhibits anti-microbial activity. Our aim, in this study, was to determine the diagnostic potential of synovial calprotectin in the diagnosis of a PJI. Patients and Methods. In this pilot study, we prospectively collected synovial fluid from the hip, knee, shoulder and elbow of 19 patients with a proven PJI and from a control group of 42 patients who underwent revision surgery without a PJI. PJI was diagnosed according to the current diagnostic criteria of the Musculoskeletal Infection Society. Synovial fluid was centrifuged and the supernatant was used to measure the level of calprotectin after applying a lateral flow immunoassay. . Results. The median synovial calprotectin level was 991 mg/L (interquartile range (IQR) 154 to 1787) in those with a PJI and 11 mg/L (IQR 3 to 29) in the control group (p < 0.0001). Using a cut-off value of 50 mg/L, this level showed an excellent diagnostic accuracy, with an area under the curve of 0.94. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was 89%, 90%, 81% and 95% respectively. The NPV was 97% in the nine patients with a chronic PJI. . Conclusion . Synovial calprotectin may be a valuable biomarker in the diagnosis of a PJI, especially in the exclusion of an infection. With a lateral flow immunoassay, a relatively rapid quantitative diagnosis can be made. The measurement is cheap and is easy to use. . Cite this article: Bone Joint J 2017;99-B:660–5

Panton-Valentine leukocidin secreted by Staphylococcus aureus is known to cause severe skin, soft tissue and lung infections. However, until recently it has not been described as causing life-threatening musculoskeletal infection. We present four patients suffering from osteomyelitis, septic arthritis, widespread intravascular thrombosis and overwhelming sepsis from proven Panton-Valentine leukocidin-secreting Staphylococcus aureus. Aggressive, early and repeated surgical intervention is required in the treatment of these patients. The Panton-Valentine leukocidin toxin not only destroys host neutrophils, immunocompromising the patient, but also increases the risk of intravascular coagulopathy. This combination leads to widespread involvement of bone with glutinous pus which is difficult to drain, and makes the delivery of antibiotics and eradication of infection very difficult without surgical intervention

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Gram-negative periprosthetic joint infection (PJI) has been poorly studied despite its rapidly increasing incidence. Treatment with one-stage revision using intra-articular (IA) infusion of antibiotics may offer a reasonable alternative with a distinct advantage of providing a means of delivering the drug in high concentrations. Carbapenems are regarded as the last line of defense against severe Gram-negative or polymicrobial infection. This study presents the results of one-stage revision using intra-articular carbapenem infusion for treating Gram-negative PJI, and analyzes the characteristics of bacteria distribution and drug sensitivity.

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Cutibacterium acnes (C. acnes; previously known as Propionibacterium acnes or P. acnes) periprosthetic hip and knee infections are under-reported. While culture contamination with C. acnes occurs, true infections are important to recognize and treat. We sought to describe the demographics and treatment outcomes of patients with C. acnes periprosthetic joint infections (PJIs) of the hip and knee.

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Accurate diagnosis of chronic periprosthetic joint infection (PJI) presents a significant challenge for hip surgeons. Preoperative diagnosis is not always easy to establish, making the intraoperative decision-making process crucial in deciding between one- and two-stage revision total hip arthroplasty (THA). Calprotectin is a promising point-of-care novel biomarker that has displayed high accuracy in detecting PJI. We aimed to evaluate the utility of intraoperative calprotectin lateral flow immunoassay (LFI) in THA patients with suspected chronic PJI.

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Histology is widely used for diagnosis of persistent infection during reimplantation in two-stage revision hip and knee arthroplasty, although data on its utility remain scarce. Therefore, this study aims to assess the predictive value of permanent sections at reimplantation in relation to reinfection risk, and to compare results of permanent and frozen sections.

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Periprosthetic joint infection (PJI) is a challenging complication of any arthroplasty procedure. We reviewed our use of static antibiotic-loaded cement spacers (ABLCSs) for staged management of PJI where segmental bone loss, ligamentous instability, or soft-tissue defects necessitate a static construct. We reviewed factors contributing to their failure and techniques to avoid these complications when using ABLCSs in this context.

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Fungal periprosthetic joint infections (PJIs) are rare, but their diagnosis and treatment are highly challenging. The purpose of this study was to investigate the clinical outcomes of patients with fungal PJIs treated with two-stage exchange knee arthroplasty combined with prolonged antifungal therapy.

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The aim of this study was to evaluate the diagnostic accuracy of the absolute synovial polymorphonuclear neutrophil cell (PMN) count for the diagnosis or exclusion of periprosthetic joint infection (PJI) after total hip (THA) or knee arthroplasty (TKA).

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Uncemented implants are now commonly used at reimplantation of a two-stage revision total hip arthoplasty (THA) following periprosthetic joint infection (PJI). However, there is a paucity of data on the performance of the most commonly used uncemented femoral implants – modular fluted tapered (MFT) femoral components – in this setting. This study evaluated implant survival, radiological results, and clinical outcomes in a large cohort of reimplantation THAs using MFT components.

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This study aims to determine difference in annual rate of early-onset (≤ 90 days) deep surgical site infection (SSI) following primary total knee arthroplasty (TKA) for osteoarthritis, and to identify risk factors that may be associated with infection.

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Despite numerous studies focusing on periprosthetic joint infections (PJIs), there are no robust data on the risk factors and timing of metachronous infections. Metachronous PJIs are PJIs that can arise in the same or other artificial joints after a period of time, in patients who have previously had PJI.

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The aim of this study was to evaluate the optimal deep tissue specimen sample number for histopathological analysis in the diagnosis of periprosthetic joint infection (PJI).

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The aim of this study was to perform the first population-based description of the epidemiological and health economic burden of fracture-related infection (FRI).

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This study aims to assess the relationship between history of pseudotumour formation secondary to metal-on-metal (MoM) implants and periprosthetic joint infection (PJI) rate, as well as establish ESR and CRP thresholds that are suggestive of infection in these patients. We hypothesized that patients with a pseudotumour were at increased risk of infection.

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Periprosthetic joint infections (PJIs) and fracture-related infections (FRIs) are associated with a significant risk of adverse events. However, there is a paucity of data on cardiac complications following revision surgery for PJI and FRI and how they impact overall mortality. Therefore, this study aimed to investigate the risk of perioperative myocardial injury (PMI) and mortality in this patient cohort.

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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.

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The aim of this study was to analyze the prevalence of culture-negative periprosthetic joint infections (PJIs) when adequate methods of culture are used, and to evaluate the outcome in patients who were treated with antibiotics for a culture-negative PJI compared with those in whom antibiotics were withheld.

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The aim of this study was to explore the relationship between reason for revision total hip arthroplasty (rTHA) and outcomes in terms of patient-reported outcome measures (PROMs).

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Septic arthritis of the hip often leads to irreversible osteoarthritis (OA) and the requirement for total hip arthroplasty (THA). The aim of this study was to report the mid-term risk of any infection, periprosthetic joint infection (PJI), aseptic revision, and reoperation in patients with a past history of septic arthritis who underwent THA, compared with a control group of patients who underwent THA for OA.

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Fungal and mycobacterial periprosthetic joint infections (PJI) are rare events. Clinicians are wary of missing these diagnoses, often leading to the routine ordering of fungal and mycobacterial cultures on periprosthetic specimens. Our goal was to examine the utility of these cultures and explore a modern bacterial culture technique using bacterial blood culture bottles (BCBs) as an alternative.

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The aim of this study was to determine the extent to which patient demographics, clinical presentation, and blood parameters vary in Kingella kingae septic arthritis when compared with those of other organisms, and whether this difference needs to be considered when assessing children in whom a diagnosis of septic arthritis is suspected.

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Single-stage revision total knee arthroplasty (rTKA) is gaining popularity in treating chronic periprosthetic joint infections (PJIs). We have introduced this approach to our clinical practice and sought to evaluate rates of reinfection and re-revision, along with predictors of failure of both single- and two-stage rTKA for chronic PJI.

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One-stage revision hip arthroplasty for periprosthetic joint infection (PJI) has several advantages; however, resection of the proximal femur might be necessary to achieve higher success rates. We investigated the risk factors for resection and re-revisions, and assessed complications and subsequent re-revisions.

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Infection complicating primary total knee arthroplasty (TKA) is a common reason for revision surgery, hospital readmission, patient morbidity, and mortality. Increasing incidence of methicillin-resistant Staphylococcus aureus (MRSA) is a particular concern. The use of vancomycin as prophylactic agent alone or in combination with cephalosporin has not demonstrated lower periprosthetic joint infection (PJI) rates, partly due to timing and dosing of intravenous (IV) vancomycin administration, which have proven important factors in effectiveness. This is a retrospective review of a consecutive series of primary TKAs examining incidence of PJI, adverse reactions, and complications using IV versus intraosseous (IO) vancomycin at 30-day, 90-day, and one-year follow-up.

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The management of periprosthetic joint infection (PJI) after total knee arthroplasty (TKA) is challenging. The correct antibiotic management remains elusive due to differences in epidemiology and resistance between countries, and reports in the literature. Before the efficacy of surgical treatment is investigated, it is crucial to analyze the bacterial strains causing PJI, especially for patients in whom no organisms are grown.

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The aim of this study was to determine the diagnostic accuracy of α defensin (AD) lateral flow assay (LFA) and enzyme-linked immunosorbent assay (ELISA) tests for periprosthetic joint infection (PJI) in comparison to conventional synovial white blood cell (WBC) count and polymorphonuclear neutrophil percentage (PMN%) analysis.

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To compare rates of serious adverse events in patients undergoing revision knee arthroplasty with consideration of the indication for revision (urgent versus elective indications), and compare these with primary arthroplasty and re-revision arthroplasty.

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To establish our early clinical results of a new total knee arthroplasty (TKA) tibial component introduced in 2013 and compare it to other designs in use at our hospital during the same period.

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Recent total knee arthroplasty (TKA) designs have featured more anatomical morphologies and shorter tibial keels. However, several reports have raised concerns about the impact of these modifications on implant longevity. The aim of this study was to report the early performance of a modern, cemented TKA design.

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.

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It can be extremely challenging to determine whether to perform reimplantation in patients who have contradictory serum inflammatory markers and frozen section results. We investigated whether patients with a positive frozen section at reimplantation were at a higher risk of reinfection despite normal ESR and CRP.

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The success rates of two-stage revision arthroplasty for infection have evolved since their early description. The implementation of internationally accepted outcome criteria led to the readjustment of such rates. However, patients who do not undergo reimplantation are usually set aside from these calculations. The aim of this study was to investigate the outcomes of two-stage revision arthroplasty when considering those who do not undergo reimplantation, and to investigate the characteristics of this subgroup.

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Removal of infected components and culture-directed antibiotics are important for the successful treatment of chronic periprosthetic joint infection (PJI). However, as many as 27% of chronic PJI patients yield negative culture results. Although culture negativity has been thought of as a contraindication to one-stage revision, data supporting this assertion are limited. The aim of our study was to report on the clinical outcomes for one-stage and two-stage exchange arthroplasty performed in patients with chronic culture-negative PJI.

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The aim of this study was to further evaluate the accuracy of ten promising synovial biomarkers (bactericidal/permeability-increasing protein (BPI), lactoferrin (LTF), neutrophil gelatinase-associated lipocalin (NGAL), neutrophil elastase 2 (ELA-2), α-defensin, cathelicidin LL-37 (LL-37), human β-defensin (HBD-2), human β-defensin 3 (HBD-3), D-dimer, and procalcitonin (PCT)) for the diagnosis of periprosthetic joint infection (PJI), and to investigate whether inflammatory joint disease (IJD) activity affects their concentration in synovial fluid.

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Metagenomic next-generation sequencing (mNGS) is useful in the diagnosis of infectious disease. However, while it is highly sensitive at identifying bacteria, it does not provide information on the sensitivity of the organisms to antibiotics. The purpose of this study was to determine whether the results of mNGS can be used to guide optimization of culture methods to improve the sensitivity of culture from intraoperative samples.

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Calprotectin (CLP) is produced in neutrophils and monocytes and released into body fluids as a result of inflammation or infection. The aim of this study was to evaluate the utility of blood and synovial CLP in the diagnosis of chronic periprosthetic joint infection (PJI).

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To evaluate the histopathological examination of peri-implant tissue samples as a technique in the diagnosis of postoperative spinal implant infection (PSII).

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Previous studies have reported an increased risk for postoperative complications in the Medicaid population undergoing total hip arthroplasty (THA). These studies have not controlled for the surgeon’s practice or patient care setting. This study aims to evaluate whether patient point of entry and Medicaid status plays a role in quality outcomes and discharge disposition following THA.

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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.

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The aim of this study was to evaluate the diagnostic value of preoperative serum CRP, white blood cell count (WBC), percentage of neutrophils (%N), and neutrophil to lymphocyte ratio (NLR) when using the fracture-related infection (FRI) consensus definition.

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The aim of this study was to determine if the local delivery of vancomycin and tobramycin in primary total knee arthroplasty (TKA) can achieve intra-articular concentrations exceeding the minimum inhibitory concentration thresholds for bacteria causing acute prosthetic joint infection (PJI).

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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.

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The aim of this study was to evaluate the diagnostic accuracy of the synovial alpha-defensin enzyme-linked immunosorbent assay (ELISA) for the diagnosis of prosthetic joint infection (PJI) in the work-up prior to revision of total hip (THA) and knee arthroplasty (TKA).

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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.

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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.

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The aim of this study was to assess the effects of transferring patients to a specialized arthroplasty centre between the first and second stages (interstage) of prosthetic joint infection (PJI) of the knee.

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While previously underappreciated, factors related to the spine contribute substantially to the risk of dislocation following total hip arthroplasty (THA). These factors must be taken into consideration during preoperative planning for revision THA due to recurrent instability. We developed a protocol to assess the functional position of the spine, the significance of these findings, and how to address different pathologies at the time of revision THA.

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There is little information regarding the risk of a patient developing prosthetic joint infection (PJI) after primary total knee arthroplasty (TKA) when the patient has previously experienced PJI of a TKA or total hip arthroplasty (THA) in another joint. The goal of this study was to compare the risk of PJI of primary TKA in this patient population against matched controls.

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The aim of this randomized trial was to compare the functional outcome of two different surgical approaches to the hip in patients with a femoral neck fracture treated with a hemiarthroplasty.

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The increasing infection burden after total hip arthroplasty (THA) has seen a rise in the use of two-stage exchange arthroplasty and the use of increasingly powerful antibiotics at the time of this procedure. As a result, there has been an increase in the number of failed two-stage revisions during the past decade. The aim of this study was to clarify the outcome of repeat two-stage revision THA following a failed two-stage exchange due to recurrent prosthetic joint infection (PJI).

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A variety of surgical approaches are used for total hip arthroplasty (THA), all with reported advantages and disadvantages. A number of common complications can occur following THA regardless of the approach used. The purpose of this study was to compare five commonly used surgical approaches with respect to the incidence of surgery-related complications.

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The aims of this study were to report the efficacy of revision surgery for patients with co-infective bacterial and fungal prosthetic joint infections (PJIs) presenting to a single institution, and to identify prognostic factors that would guide management.

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The aim of this review was to evaluate the available literature and to calculate the pooled sensitivity and specificity for the different alpha-defensin test systems that may be used to diagnose prosthetic joint infection (PJI).

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

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In 2013, we introduced a specialized, centralized, and interdisciplinary team in our institution that applied a standardized diagnostic and treatment algorithm for the management of prosthetic joint infections (PJIs). The hypothesis for this study was that the outcome of treatment would be improved using this approach.

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To assess the diagnostic value of C-reactive protein (CRP), leucocyte count (LC), and erythrocyte sedimentation rate (ESR) in late fracture-related infection (FRI).

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α-defensin is a biomarker which has been described as having a high degree of accuracy in the diagnosis of periprosthetic joint infection (PJI). Current meta-analyses are based on the α-defensin laboratory-based immunoassay rather than the quick on-table lateral flow test kit. This study is the first meta-analysis to compare the accuracy of the α-defensin laboratory-based immunoassay and the lateral flow test kit for the diagnosis of PJI.

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To evaluate the effectiveness of an institutionally developed algorithm for evaluation and diagnosis of prosthetic joint injection and to determine the impact of this protocol on overall hospital re-admissions.p

Periprosthetic joint infection (PJI) is a devastating complication for patients and results in greatly increased costs of care for both healthcare providers and patients. More than 15 500 revision hip and knee procedures were recorded in England, Wales and Northern Ireland in 2013, with infection accounting for 13% of revision hip and 23% of revision knee procedures.

We report our experience of using antibiotic eluting absorbable calcium sulphate beads in 15 patients (eight men and seven women with a mean age of 64.8 years; 41 to 83) as part of a treatment protocol for PJI in revision arthroplasty.

The mean follow-up was 16 months (12 to 22). We report the outcomes and complications, highlighting the risk of hypercalcaemia which occurred in three patients.

We recommend that serum levels of calcium be routinely sought following the implantation of absorbable calcium sulphate beads in orthopaedic surgery.

Cite this article: Bone Joint J 2015;97-B:1237–41.

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We compared the outcome of total hip arthroplasty (THA) in obese patients who previously underwent bariatric surgery and those who did not, in a matched cohort study.

Non-tuberculous mycobacterial (NTM) infection of the musculoskeletal tissue is a rare disease. An early and accurate diagnosis is often difficult because of the indolent clinical course and difficulty of isolating pathogens. Our goal was to determine the clinical features of musculoskeletal NTM infection and to present the treatment outcomes. A total of 29 patients (nine females, 20 males between 34 and 85 years old, mean age 61.7 years; 34 to 85) with NTM infection of the musculoskeletal system between 1998 to 2011 were identified and their treatment retrospectively analysed. Microbiological studies demonstrated NTM in 29 patients: the isolates were Mycobacterium intracellulare in six patients, M. fortuitum in three, M. abscessus in two and M. marinum in one. In the remaining patients we failed to identify the species. The involved sites were the hand/wrist in nine patients the knee in five patients, spine in four patients, foot in two patients, elbow in two patients, shoulder in one, ankle in two patients, leg in three patients and multiple in one patient. The mean interval between the appearance of symptoms and diagnosis was 20.8 months (1.5 to 180). All patients underwent surgical treatment and antimicrobial medication according to our protocol for chronic musculoskeletal infection: 20 patients had NTM-specific medication and nine had conventional antimicrobial therapy. At the final follow-up 22 patients were cured, three failed to respond to treatment and four were lost to follow-up. Identifying these diseases due the initial non-specific presentation can be difficult. Treatment consists of surgical intervention and adequate antimicrobial therapy, which can result in satisfactory outcomes.

Cite this article: Bone Joint J 2014;96-B:1561–5.

Periprosthetic joint infection (PJI) is one of the most feared and challenging complications following total knee arthroplasty. We provide a detailed description of our current understanding regarding the management of PJI of the knee, including diagnostic aids, pre-operative planning, surgical treatment, and outcome.

Cite this article: Bone Joint J 2015;97-B(10 Suppl A):20–9.