Aims. This aim of this study was to analyze the detection rate of rare pathogens in bone and joint infections (BJIs) using metagenomic next-generation sequencing (mNGS), and the impact of mNGS on clinical diagnosis and treatment. Methods. A retrospective analysis was conducted on 235 patients with BJIs who were treated at our hospital between January 2015 and December 2021. Patients were divided into the no-mNGS group (microbial culture only) and the mNGS group (mNGS testing and microbial culture) based on whether mNGS testing was used or not. Results. A total of 147 patients were included in the no-mNGS group and 88 in the mNGS group. The mNGS group had a higher detection rate of rare pathogens than the no-mNGS group (21.6% vs 10.2%, p = 0.016). However, the mNGS group had lower rates of antibiotic-related complications, shorter hospital stays, and higher infection control rates compared with the no-mNGS group (p = 0.017, p = 0.003, and p = 0.028, respectively), while there was no significant difference in the duration of antibiotic use (p = 0.957). In culture-negative cases, the mNGS group had lower rates of antibiotic-related complications, shorter hospital stays, and a higher infection control rate than the no-mNGS group (p = 0.036, p = 0.033, p = 0.022, respectively), while there was no significant difference in the duration of antibiotic use (p = 0.748). Conclusion. mNGS improves detection of rare pathogens in BJIs. mNGS testing reduces antibiotic-related complications, shortens hospital stay and antibiotic use duration, and improves treatment success rate, benefits which are particularly evident in culture-negative cases. Cite this article: Bone Joint Res 2024;13(8):401–410

Aims. Bacteriophages infect, replicate inside bacteria, and are released from the host through lysis. Here, we evaluate the effects of repetitive doses of the Staphylococcus aureus phage 191219 and gentamicin against haematogenous and early-stage biofilm implant-related infections in Galleria mellonella. Methods. For the haematogenous infection, G. mellonella larvae were implanted with a Kirschner wire (K-wire), infected with S. aureus, and subsequently phages and/or gentamicin were administered. For the early-stage biofilm implant infection, the K-wires were pre-incubated with S. aureus suspension before implantation. After 24 hours, the larvae received phages and/or gentamicin. In both models, the larvae also received daily doses of phages and/or gentamicin for up to five days. The effect was determined by survival analysis for five days and quantitative culture of bacteria after two days of repetitive doses. Results. In the haematogenous infection, a single combined dose of phages and gentamicin, and repetitive injections with gentamicin or in combination with phages, resulted in significantly improved survival rates. In the early-stage biofilm infection, only repetitive combined administration of phages and gentamicin led to a significantly increased survival. Additionally, a significant reduction in number of bacteria was observed in the larvae after receiving repetitive doses of phages and/or gentamicin in both infection models. Conclusion. Based on our results, a single dose of the combination of phages and gentamicin is sufficient to prevent a haematogenous S. aureus implant-related infection, whereas gentamicin needs to be administered daily for the same effect. To treat early-stage S. aureus implant-related infection, repetitive doses of the combination of phages and gentamicin are required. Cite this article: Bone Joint Res 2024;13(8):383–391

Aims. It is well described that patients with bone and joint infections (BJIs) commonly experience significant functional impairment and disability. Published literature is lacking on the impact of BJIs on mental health. Therefore, the aim of this study was to assess health-related quality of life (HRQoL) and the impact on mental health in patients with BJIs. Methods. The AO Trauma Infection Registry is a prospective multinational registry. In total, 229 adult patients with long-bone BJI were enrolled between 1 November 2012 and 31 August 2017 in 18 centres from ten countries. Clinical outcome data, demographic data, and details on infections and treatments were collected. Patient-reported outcomes using the 36-Item Short-Form Health Survey questionnaire (SF-36), Parker Mobility Score, and Katz Index of Independence in Activities of Daily Living were assessed at one, six, and 12 months. The SF-36 mental component subscales were analyzed and correlated with infection characteristics and clinical outcome. Results. The SF-36 physical component summary mean at baseline was 30.9 (95% CI 29.7 to 32.0). At one month, it was unchanged (30.5; 95% CI 29.5 to 31.5; p = 0.447); it had improved statistically significantly at six months (35.5; 95% CI 34.2 to 36.7; p < 0.001) and at 12 months (37.9; 95% CI 36.4 to 39.3; p < 0.001). The SF-36 mental component summary mean at baseline was 42.5 (95% CI 40.8 to 44.2). At one month, it was unchanged (43.1; 95% CI 41.4 to 44.8; p = 0.458); it had improved statistically significantly at six months (47.1; 95% CI 45.4 to 48.7; p < 0.001) and at 12 months (46.7; 95% CI 45.0 to 48.5; p < 0.001). All mental subscales had improved by the end of the study, but mental health status remained compromised in comparison with the average USA population. Conclusion. BJIs considerably impact HRQoL, particularly mental health. Patients suffering from BJIs reported considerable limitations in their daily and social activities due to psychological problems. Impaired mental health may be explained by the chronic nature of BJIs, and therefore the mental wellbeing of these patients should be monitored closely. Cite this article: Bone Jt Open 2024;5(9):721–728

Aims. This study aimed to evaluate the clinical application of the PJI-TNM classification for periprosthetic joint infection (PJI) by determining intraobserver and interobserver reliability. To facilitate its use in clinical practice, an educational app was subsequently developed and evaluated. Methods. A total of ten orthopaedic surgeons classified 20 cases of PJI based on the PJI-TNM classification. Subsequently, the classification was re-evaluated using the PJI-TNM app. Classification accuracy was calculated separately for each subcategory (reinfection, tissue and implant condition, non-human cells, and morbidity of the patient). Fleiss’ kappa and Cohen’s kappa were calculated for interobserver and intraobserver reliability, respectively. Results. Overall, interobserver and intraobserver agreements were substantial across the 20 classified cases. Analyses for the variable ‘reinfection’ revealed an almost perfect interobserver and intraobserver agreement with a classification accuracy of 94.8%. The category 'tissue and implant conditions' showed moderate interobserver and substantial intraobserver reliability, while the classification accuracy was 70.8%. For 'non-human cells,' accuracy was 81.0% and interobserver agreement was moderate with an almost perfect intraobserver reliability. The classification accuracy of the variable 'morbidity of the patient' reached 73.5% with a moderate interobserver agreement, whereas the intraobserver agreement was substantial. The application of the app yielded comparable results across all subgroups. Conclusion. The PJI-TNM classification system captures the heterogeneity of PJI and can be applied with substantial inter- and intraobserver reliability. The PJI-TNM educational app aims to facilitate application in clinical practice. A major limitation was the correct assessment of the implant situation. To eliminate this, a re-evaluation according to intraoperative findings is strongly recommended. Cite this article: Bone Joint Res 2024;13(1):19–27

Aims. 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. Methods. This is a retrospective population-based cohort study using prospectively collected patient-level data between 1 January 2013 and 1 March 2020. The diagnosis of deep SSI was defined as per the Centers for Disease Control/National Healthcare Safety Network criteria. The Mann-Kendall Trend test was used to detect monotonic trends in annual rates of early-onset deep SSI over time. Multiple logistic regression was used to analyze the effect of different patient, surgical, and healthcare setting factors on the risk of developing a deep SSI within 90 days from surgery for patients with complete data. We also report 90-day mortality. Results. A total of 39,038 patients underwent primary TKA for osteoarthritis during the study period. Of these, 275 patients developed a deep SSI within 90 days of surgery, representing a cumulative incidence of 0.7%. The annual infection rate did not significantly decrease over the seven-year study period (p = 0.162). Overall, 13,885 (35.5%) cases were excluded from the risk analysis due to missing data. Risk factors associated with early-onset deep SSI included male sex, American Society of Anesthesiologists grade ≥ 3, blood transfusion, acute length of stay, and surgeon volume < 30 TKAs/year. Early-onset deep SSI was not associated with increased 90-day mortality. Conclusion. This study establishes a reliable baseline infection rate for early-onset deep SSI after TKA for osteoarthritis using robust Infection Prevention and Control surveillance data, and identifies several potentially modifiable risk factors. Cite this article: Bone Joint J 2023;105-B(9):971–976

Aims. Arthroplasty surgery of the knee and hip is performed in two to three million patients annually. Periprosthetic joint infections occur in 4% of these patients. Debridement, antibiotics, and implant retention (DAIR) surgery aimed at cleaning the infected prosthesis often fails, subsequently requiring invasive revision of the complete prosthetic reconstruction. Infection-specific imaging may help to guide DAIR. In this study, we evaluated a bacteria-specific hybrid tracer (. 99m. Tc-UBI. 29-41. -Cy5) and its ability to visualize the bacterial load on femoral implants using clinical-grade image guidance methods. Methods. 99m. Tc-UBI. 29-41. -Cy5 specificity for Stapylococcus aureus was assessed in vitro using fluorescence confocal imaging. Topical administration was used to highlight the location of S. aureus cultured on femoral prostheses using fluorescence imaging and freehand single photon emission CT (fhSPECT) scans. Gamma counting and fhSPECT were used to quantify the bacterial load and monitor cleaning with chlorhexidine. Microbiological culturing helped to relate the imaging findings with the number of (remaining) bacteria. Results. Bacteria could be effectively stained in vitro and on prostheses, irrespective of the presence of biofilm. Infected prostheses revealed bacterial presence on the transition zone between the head and neck, and in the screw hole. Qualitative 2D fluorescence images could be complemented with quantitative 3D fhSPECT scans. Despite thorough chlorhexidine treatments, 28% to 44% of the signal remained present in the locations of the infection that were identified using imaging, which included 500 to 2,000 viable bacteria. Conclusion. The hybrid tracer . 99m. Tc-UBI. 29-41. -Cy5 allowed effective bacterial staining. Qualitative real-time fluorescence guidance could be effectively combined with nuclear imaging that enables quantitative monitoring of the effectiveness of cleaning strategies. Cite this article: Bone Joint Res 2023;12(1):72–79

Periprosthetic joint infection (PJI) remains an extremely challenging complication. We have focused on this issue more over the last decade than previously, but there are still many unanswered questions. We now have a workable definition that everyone should align to, but we need to continue to focus on identifying the organisms involved. Surgical strategies are evolving and care is becoming more patient-centred. There are some good studies under way. There are, however, still numerous problems to resolve, and the challenge of PJI remains a major one for the orthopaedic community. This annotation provides some up-to-date thoughts about where we are, and the way forward. There is still scope for plenty of research in this area. Cite this article: Bone Joint J 2022;104-B(11):1193–1195

Aims. 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. Methods. We retrospectively reviewed 32 patients (22 hips and 11 knees) who underwent single-stage revision combined with IA carbapenem infusion between November 2013 and March 2020. The IA and intravenous (IV) carbapenem infusions were administered for a single Gram-negative infection, and IV vancomycin combined with IA carbapenems and vancomycin was applied for polymicrobial infection including Gram-negative bacteria. The bacterial community distribution, drug sensitivity, infection control rate, functional recovery, and complications were evaluated. Reinfection or death caused by PJI was regarded as a treatment failure. Results. Gram-negative PJI was mainly caused by Escherichia coli (8/34), Enterobacter cloacae (7/34), and Klebsiella pneumoniae (5/34). Seven cases (7/32) involved polymicrobial PJIs. The resistance rates of penicillin, cephalosporin, quinolones, and sulfonamides were > 10%, and all penicillin and partial cephalosporins (first and second generation) were > 30%. Of 32 cases, treatment failed to eradicate infection in only three cases (9.4%), at a mean follow-up of 55.1 months (SD 25 to 90). The mean postoperative Harris Hip Score and Hospital for Special Surgery knee score at the most recent follow-up were 81 (62 to 91) and 79 (56 to 89), respectively. One patient developed a fistula, and another presented with a local rash on an infected joint. Conclusion. The use of IA carbapenem delivered alongside one-stage revision effectively controlled Gram-negative infection and obtained acceptable clinical outcomes with few complications. Notably, first- and second-generation cephalosporins and penicillin should be administrated with caution, due to a high incidence of resistance. Cite this article: Bone Joint J 2023;105-B(3):284–293

Aims. The aim of this study was to determine the prevalence of depressive and anxiety disorders prior to total hip (THA) and total knee arthroplasty (TKA) and to assess their impact on the rates of any infection, revision, or reoperation. Methods. Between January 2000 and March 2019, 21,469 primary and revision arthroplasties (10,011 THAs; 11,458 TKAs), which were undertaken in 15,504 patients at a single academic medical centre, were identified from a 27-county linked electronic medical record (EMR) system. Depressive and anxiety disorders were identified by diagnoses in the EMR or by using a natural language processing program with subsequent validation from review of the medical records. Patients with mental health diagnoses other than anxiety or depression were excluded. Results. Depressive and/or anxiety disorders were common before THA and TKA, with a prevalence of 30% in those who underwent primary THA, 33% in those who underwent revision THA, 32% in those who underwent primary TKA, and 35% in those who underwent revision TKA. The presence of depressive or anxiety disorders was associated with a significantly increased risk of any infection (primary THA, hazard ratio (HR) 1.5; revision THA, HR 1.9; primary TKA, HR 1.6; revision TKA, HR 1.8), revision (THA, HR 1.7; TKA, HR 1.6), re-revision (THA, HR 2.0; TKA, HR 1.6), and reoperation (primary THA, HR 1.6; revision THA, HR 2.2; primary TKA, HR 1.4; revision TKA, HR 1.9; p < 0.03 for all). Patients with preoperative depressive and/or anxiety disorders were significantly less likely to report “much better” joint function after primary THA (78% vs 87%) and primary TKA (86% vs 90%) compared with those without these disorders at two years postoperatively (p < 0.001 for all). Conclusion. The presence of depressive or anxiety disorders prior to primary or revision THA and TKA is common, and associated with a significantly higher risk of infection, revision, reoperation, and dissatisfaction. This topic deserves further study, and surgeons may consider mental health optimization to be of similar importance to preoperative variables such as diabetic control, prior to arthroplasty. Cite this article: Bone Joint J 2023;105-B(5):526–533

Aims. Achievement of accurate microbiological diagnosis prior to revision is key to reducing the high rates of persistent infection after revision knee surgery. The effect of change in the microorganism between the first- and second-stage revision of total knee arthroplasty for periprosthetic joint infection (PJI) on the success of management is not clear. Methods. A two-centre retrospective cohort study was conducted to review the outcome of patients who have undergone two-stage revision for treatment of knee arthroplasty PJI, focusing specifically on isolated micro-organisms at both the first- and second-stage procedure. Patient demographics, medical, and orthopaedic history data, including postoperative outcomes and subsequent treatment, were obtained from the electronic records and medical notes. Results. The study cohort consisted of 84 patients, of whom 59.5% (n = 50) had successful eradication of their infection at a mean follow-up of 4.7 years. For the 34 patients who had recurrence of infection, 58.8% (n = 20) had a change in isolated organism, compared to 18% (n = 9) in the infection eradication group (p < 0.001). When adjusting for confound, there was no association when the growth on the second stage was the same as the first (odd ratio (OR) 2.50, 95% confidence interval (CI) 0.49 to 12.50; p = 0.269); however, when a different organism was identified at the second stage, this was independently associated with failure of treatment (OR 8.40, 95% CI 2.91 to 24.39; p < 0.001). There were no other significant differences between the two cohorts with regard to patient demographics or type of organisms isolated. Conclusion. Change in the identified microorganism between first- and second-stage revision for PJI was associated with failure of management. Identification of this change in the microorganism prior to commencement of the second stage may help target antibiotic management and could improve the success of surgery in these patients. Cite this article: Bone Jt Open 2023;4(9):720–727

Aims. Hand trauma, consisting of injuries to both the hand and the wrist, are a common injury seen worldwide. The global age-standardized incidence of hand trauma exceeds 179 per 100,000. Hand trauma may require surgical management and therefore result in significant costs to both healthcare systems and society. Surgical site infections (SSIs) are common following all surgical interventions, and within hand surgery the risk of SSI is at least 5%. SSI following hand trauma surgery results in significant costs to healthcare systems with estimations of over £450 per patient. The World Health Organization (WHO) have produced international guidelines to help prevent SSIs. However, it is unclear what variability exists in the adherence to these guidelines within hand trauma. The aim is to assess compliance to the WHO global guidelines in prevention of SSI in hand trauma. Methods. This will be an international, multicentre audit comparing antimicrobial practices in hand trauma to the standards outlined by WHO. Through the Reconstructive Surgery Trials Network (RSTN), hand surgeons across the globe will be invited to participate in the study. Consultant surgeons/associate specialists managing hand trauma and members of the multidisciplinary team will be identified at participating sites. Teams will be asked to collect data prospectively on a minimum of 20 consecutive patients. The audit will run for eight months. Data collected will include injury details, initial management, hand trauma team management, operation details, postoperative care, and antimicrobial techniques used throughout. Adherence to WHO global guidelines for SSI will be summarized using descriptive statistics across each criteria. Discussion. The Hand and Wrist trauma: Antimicrobials and Infection Audit of Clinical Practice (HAWAII ACP) will provide an understanding of the current antimicrobial practice in hand trauma surgery. This will then provide a basis to guide further research in the field. The findings of this study will be disseminated via conference presentations and a peer-reviewed publication. Cite this article: Bone Jt Open 2024;5(4):361–366

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

Aims. 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. Methods. A multicentre observational study was undertaken: 1,553 acute and 1,556 chronic PJIs, diagnosed between 2013 and 2018, were retrospectively analyzed. Culture-negative PJIs were diagnosed according to the Muskuloskeletal Infection Society (MSIS), International Consensus Meeting (ICM), and European Bone and Joint Society (EBJIS) definitions. The primary outcome was recurrent infection, and the secondary outcome was removal of the prosthetic components for any indication, both during a follow-up period of two years. Results. None of the acute PJIs and 70 of the chronic PJIs (4.7%) were culture-negative; a total of 36 culture-negative PJIs (51%) were treated with antibiotics, particularly those with histological signs of infection. After two years of follow-up, no recurrent infections occurred in patients in whom antibiotics were withheld. The requirement for removal of the components for any indication during follow-up was not significantly different in those who received antibiotics compared with those in whom antibiotics were withheld (7.1% vs 2.9%; p = 0.431). Conclusion. When adequate methods of culture are used, the incidence of culture-negative PJIs is low. In patients with culture-negative PJI, antibiotic treatment can probably be withheld if there are no histological signs of infection. In all other patients, diagnostic efforts should be made to identify the causative microorganism by means of serology or molecular techniques. Cite this article: Bone Joint J 2022;104-B(1):183–188

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 efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders. Methods. Air pouches created in female BalBc mice by subcutaneous injection of air. In the first of two independent studies, pouches were implanted with titanium cylinders (400, 700, and 100 µm pore sizes) and inoculated with Staphylococcus aureus (1 × 10. 3. or 1 × 10. 6. colony-forming units (CFU)/pouch) to establish infection and biofilm formation. Mice were killed after one week for microbiological analysis. In the second study, pouches were implanted with 400 µm titanium cylinders and inoculated with S. aureus (1 × 10. 3. or 1 × 10. 6. CFU/pouch). Four groups were tested: 1) no bacteria; 2) bacteria without saline wash; 3) saline wash only; and 4) saline wash plus PVA-VAN/TOB-P. After seven days, the pouches were opened and washed with saline alone, or had an additional injection of PVA-VAN/TOB-P. Mice were killed 14 days after pouch wash. Results. The first part of the study showed that low-grade infection was more significant in 400 µm cylinders than cylinders with larger pore sizes (p < 0.05). The second part of the study showed that saline wash alone was ineffective in eradicating both low- and high-grade infections. Saline plus PVA-VAN/TOB-P eradicated the titanium cylinder-associated infections, as manifested by negative cultures of the washouts and supported by scanning electron microscopy and histology. Conclusion. Porous titanium cylinders were vulnerable to bacterial infection and biofilm formation that could not be treated by saline irrigation alone. Application of PVA-VAN/TOB-P directly into the surgical site alone or after saline wash represents a feasible approach for prevention and/or treatment of porous implant-related infections. Cite this article: Bone Joint Res 2024;13(11):622–631

Aims. 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. Methods. We prospectively included consecutive patients at high cardiovascular risk (defined as age ≥ 45 years with pre-existing coronary, peripheral, or cerebrovascular artery disease, or any patient aged ≥ 65 years, plus a postoperative hospital stay of > 24 hours) undergoing septic or aseptic major orthopaedic surgery between July 2014 and October 2016. All patients received a systematic screening to reliably detect PMI, using serial measurements of high-sensitivity cardiac troponin T. All-cause mortality was assessed at one year. Multivariable logistic regression models were applied to compare incidence of PMI and mortality between patients undergoing septic revision surgery for PJI or FRI, and patients receiving aseptic major bone and joint surgery. Results. In total, 911 consecutive patients were included. The overall perioperative myocardial injury (PMI) rate was 15.4% (n = 140). Septic revision surgery for PJI was associated with a significantly higher PMI rate (43.8% (14/32) vs 14.5% (57/393); p = 0.001) and one-year mortality rate (18.6% (6/32) vs 7.4% (29/393); p = 0.038) compared to aseptic revision or primary arthroplasty. The association with PMI persisted in multivariable analysis with an adjusted odds ratio (aOR) of 4.7 (95% confidence interval (CI) 2.1 to 10.7; p < 0.001), but was not statistically significant for one-year mortality (aOR 1.9 (95% CI 0.7 to 5.4; p = 0.240). PMI rate (15.2% (5/33) vs 14.1% (64/453)) and one-year mortality (15.2% (5/33) vs 9.1% (41/453)) after FRI revision surgery were comparable to aseptic long-bone fracture surgery. Conclusion. Patients undergoing revision surgery for PJI were at a risk of PMI and death compared to those undergoing aseptic arthroplasty surgery. Screening for PMI and treatment in specialized multidisciplinary units should be considered in major bone and joint infections. Cite this article: Bone Joint J 2022;104-B(6):696–702

Aims. Orthopaedic infection is a potentially serious complication of elective and emergency trauma and orthopaedic procedures, with a high associated burden of morbidity and cost. Optimization of vitamin D levels has been postulated to be beneficial in the prevention of orthopaedic infection. This study explores the role of vitamin D in orthopaedic infection through a systematic review of available evidence. Methods. A comprehensive search was conducted on databases including Medline and Embase, as well as grey literature such as Google Scholar and The World Health Organization Database. Pooled analysis with weighted means was undertaken. Results. Pooled analysis of four studies including 651 patients found the mean 25(OH)D level to be 50.7 nmol/l with a mean incidence of infection of 70%. There was a paucity of literature exploring prophylactic 25(OH)D supplementation on reducing orthopaedic infection, however, there was evidence of association between low 25(OH)D levels and increased incidence of orthopaedic infection. Conclusion. The results indicate a significant proportion of orthopaedic patients have low 25(OH]D levels, as well as an association between low 25(OH)D levels and orthopaedic infection, but more randomized controlled trials need to be conducted to establish the benefit of prophylactic supplementation and the optimum regimen by dose and time. Cite this article: Bone Jt Open 2021;2(9):721–727

Aims. Trained immunity confers non-specific protection against various types of infectious diseases, including bone and joint infection. Platelets are active participants in the immune response to pathogens and foreign substances, but their role in trained immunity remains elusive. Methods. We first trained the innate immune system of C57BL/6 mice via intravenous injection of two toll-like receptor agonists (zymosan and lipopolysaccharide). Two, four, and eight weeks later, we isolated platelets from immunity-trained and control mice, and then assessed whether immunity training altered platelet releasate. To better understand the role of immunity-trained platelets in bone and joint infection development, we transfused platelets from immunity-trained mice into naïve mice, and then challenged the recipient mice with Staphylococcus aureus or Escherichia coli. Results. After immunity training, the levels of pro-inflammatory cytokines (tumour necrosis factor alpha (TNF-α), interleukin (IL)-17A) and chemokines (CCL5, CXCL4, CXCL5, CXCL7, CXCL12) increased significantly in platelet releasate, while the levels of anti-inflammatory cytokines (IL-4, IL-13) decreased. Other platelet-secreted factors (e.g. platelet-derived growth factor (PDGF)-AA, PDGF-AB, PDGF-BB, cathepsin D, serotonin, and histamine) were statistically indistinguishable between the two groups. Transfusion of platelets from trained mice into naïve mice reduced infection risk and bacterial burden after local or systemic challenge with either S. aureus or E. coli. Conclusion. Immunity training altered platelet releasate by increasing the levels of inflammatory cytokines/chemokines and decreasing the levels of anti-inflammatory cytokines. Transfusion of platelets from immunity-trained mice conferred protection against bone and joint infection, suggesting that alteration of platelet releasate might be an important mechanism underlying trained immunity and may have clinical implications. Cite this article: Bone Joint Res 2022;11(2):73–81

Aims. Fracture-related infections (FRIs) are a devastating complication of fracture management. However, the impact of FRIs on mental health remains understudied. The aim of this study was a longitudinal evaluation of patients’ psychological state, and expectations for recovery comparing patients with recurrent FRI to those with primary FRI. Methods. A prospective longitudinal study was conducted at a level 1 trauma centre from January 2020 to December 2022. In total, 56 patients treated for FRI were enrolled. The ICD-10 symptom rating (ISR) and an expectation questionnaire were assessed at five timepoints: preoperatively, one month postoperatively, and at three, six, and 12 months. Results. Recurrent FRI cases consistently exceeded the symptom burden threshold (0.60) in ISR scores at all assessment points. The difference between preoperative-assessed total ISR scores and the 12-month follow-up was not significant in either group, with 0.04 for primary FRI (p = 0.807) and 0.01 for recurrent FRI (p = 0.768). While primary FRI patients showed decreased depression scores post surgery, recurrent FRI cases experienced an increase, reaching a peak at 12 months (1.92 vs 0.94; p < 0.001). Anxiety scores rose for both groups after surgery, notably higher in recurrent FRI cases (1.39 vs 1.02; p < 0.001). Moreover, patients with primary FRI reported lower expectations of returning to normal health at three (1.99 vs 1.11; p < 0.001) and 12 months (2.01 vs 1.33; p = 0.006). Conclusion. The findings demonstrate the significant psychological burden experienced by individuals undergoing treatment for FRI, which is more severe in recurrent FRI. Understanding the psychological dimensions of recurrent FRIs is crucial for comprehensive patient care, and underscores the importance of integrating psychological support into the treatment paradigm for such cases. Cite this article: Bone Jt Open 2024;5(7):621–627

Aims. Serum inflammatory parameters are widely used to aid in diagnosing a periprosthetic joint infection (PJI). Due to their limited performances in the literature, novel and more accurate biomarkers are needed. Serum albumin-to-globulin ratio (AGR) and serum CRP-to-albumin ratio (CAR) have previously been proposed as potential new parameters, but results were mixed. The aim of this study was to assess the diagnostic accuracy of AGR and CAR in diagnosing PJI and to compare them to the established and widely used marker CRP. Methods. From 2015 to 2022, a consecutive series of 275 cases of revision total hip (n = 129) and knee arthroplasty (n = 146) were included in this retrospective cohort study. Based on the 2021 European Bone and Joint Infection Society (EBJIS) definition, 144 arthroplasties were classified as septic. Using receiver operating characteristic curve (ROC) analysis, the ideal thresholds and diagnostic performances were calculated. The areas under the curve (AUCs) were compared using the z-test. Results. AGR, CAR, and CRP were associated with PJI (p < 0.001). Sensitivities were 62.5% (95% CI 54.3 to 70.0), 73.6% (95% CI 65.8 to 80.1), and 71.5% (95% CI 63.6 to 78.3), respectively. Specificities were calculated with 84.7% (95% CI 77.5 to 89.9), 86.3% (95% CI 79.2 to 91.2), and 87.8% (95% CI 80.9 to 92.4), respectively. The AUC of CRP (0.797 (95% CI 0.750 to 0.843)) was significantly higher than the AUC of AGR (0.736 (95% CI 0.686 to 0.786), p < 0.001), and similar to AUC of CAR (0.799 (95% CI 0.753 to 0.846), p = 0.832). Decreased sensitivities were observed in PJIs caused by low-virulence organisms (AGR: 60%, CAR: 78%) compared to high-virulence pathogens (AGR: 80%, p = 0.042; CAR: 88%, p = 0.158). Higher sensitivities were seen in acute haematogenous (AGR: 83%, CAR: 96%) compared to chronic PJIs (AGR: 54%, p = 0.001; CAR: 65%, p < 0.001). Conclusion. Serum AGR and CAR showed limited diagnostic accuracy (especially in low-grade and chronic infections) and did not outperform the established marker CRP in our study. Hence, neither parameter can be recommended as an additional tool for diagnosing PJI. Cite this article: Bone Joint Res 2024;13(8):372–382