Aims. Advances in treatment have extended the life expectancy of patients with metastatic bone disease (MBD). Patients could experience more skeletal-related events (SREs) as a result of this progress. Those who have already experienced a SRE could encounter another local management for a subsequent SRE, which is not part of the treatment for the initial SRE. However, there is a noted gap in research on the rate and characteristics of subsequent SREs requiring further localized treatment, obligating clinicians to extrapolate from experiences with initial SREs when confronting subsequent ones. This study aimed to investigate the proportion of MBD patients developing subsequent SREs requiring local treatment, examine if there are prognostic differences at the initial treatment between those with single versus subsequent SREs, and determine if clinical, oncological, and prognostic features differ between initial and subsequent SRE treatments. Methods. This retrospective study included 3,814 adult patients who received local treatment – surgery and/or radiotherapy – for bone metastasis between 1 January 2010 and 31 December 2019. All included patients had at least one SRE requiring local treatment. A subsequent SRE was defined as a second SRE requiring local treatment. Clinical, oncological, and prognostic features were compared between single SREs and subsequent SREs using Mann-Whitney U test, Fisher’s exact test, and Kaplan–Meier curve. Results. Of the 3,814 patients with SREs, 3,159 (83%) patients had a single SRE and 655 (17%) patients developed a subsequent SRE. Patients who developed subsequent SREs generally had characteristics that favoured longer survival, such as higher BMI, higher albumin levels, fewer comorbidities, or lower neutrophil count. Once the patient got to the point of subsequent SRE, their clinical and oncological characteristics and one-year survival (28%) were not as good as those with only a single SRE (35%; p < 0.001), indicating that clinicians’ experiences when treating the initial SRE are not similar when treating a subsequent SRE. Conclusion. This study found that 17% of patients required treatments for a second, subsequent SRE, and the current clinical guideline did not provide a specific approach to this clinical condition. We observed that referencing the initial treatment, patients in the subsequent SRE group had longer six-week, 90-day, and one-year median survival than patients in the single SRE group. Once patients develop a subsequent SRE, they have a worse one-year survival rate than those who receive treatment for a single SRE. Future research should identify prognostic factors and assess the applicability of existing survival prediction models for better management of subsequent SREs. Cite this article: Bone Joint Res 2024;13(9):497–506

Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes – the main cellular components in BMAC – interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes.

Cite this article: Bone Joint Res 2024;13(9):462–473.

Aims. Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers. Methods. We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI. Results. Patients with confirmed PJI had significantly increased levels of NET markers (cfDNA (p < 0.001), calprotectin (p < 0.001), and neutrophil elastase (p = 0.022)) and inflammation markers (IL-6; p < 0.001) in plasma. Moreover, the plasma of patients with PJI induced significantly more neutrophil activation than the plasma of the controls (p < 0.001) independently of tumour necrosis factor alpha. Patients with PJI also had a reduced DNaseI activity in plasma (p < 0.001), leading to a significantly impaired degradation of NETs (p < 0.001). This could be therapeutically restored with recombinant human DNaseI to the level in the controls. We developed a model to improve the diagnosis of PJI with cfDNA, calprotectin, and the start tail of TGT as predictors, though cfDNA alone achieved a good prediction and is simpler to measure. Conclusion. We confirmed that patients with PJI have an increased level of NETosis in plasma. Their plasma both induced NET release and had an impaired ability to degrade NETs mediated by a reduced DNaseI activity. This can be therapeutically restored in vitro with the approved Dornase alfa, Pulmozyme, which may allow novel methods of treatment. A combination of NETs and haemostatic biomarkers could improve the diagnosis of PJI, especially those patients in whom this diagnosis is uncertain. Cite this article: Bone Joint J 2024;106-B(9):1021–1030

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.

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.

Aims

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

Aims

Adenosine, lidocaine, and Mg²⁺ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Aims. The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies. Methods. A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase. Results. The early fxH proteome was characterized by immunomodulatory and osteogenic proteins, and proteins involved in the coagulation cascade. Treatment-specific proteome alterations were observed. The fxH proteome of the ETC group showed increased expression of pro-inflammatory proteins related to, among others, activation of the complement system, neutrophil functioning, and macrophage activation, while showing decreased expression of proteins related to osteogenesis and tissue remodelling. Conversely, the fxH proteome of the DCO group contained various upregulated or exclusively detected proteins related to tissue regeneration and remodelling, and proteins related to anti-inflammatory and osteogenic processes. Conclusion. The early fxH proteome of the ETC group was characterized by the expression of immunomodulatory, mainly pro-inflammatory, proteins, whereas the early fxH proteome of the DCO group was more regenerative and osteogenic in nature. These findings match clinical observations, in which enhanced surgical trauma after multiple trauma causes dysbalanced inflammation, potentially leading to reduced tissue regeneration, and gained insights into regulatory mechanisms of fracture healing after severe trauma. Cite this article: Bone Joint Res 2024;13(5):214–225

Aims

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.

Aims

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.

Aims

This study aimed to explore the biological and clinical importance of dysregulated key genes in osteoarthritis (OA) patients at the cartilage level to find potential biomarkers and targets for diagnosing and treating OA.

Aims

This study aimed to compare the performance of survival prediction models for bone metastases of the extremities (BM-E) with pathological fractures in an Asian cohort, and investigate patient characteristics associated with survival.

Aims

Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown.

Aims. The diagnosis of periprosthetic joint infection (PJI) can be challenging as the symptoms are similar to other conditions, and the markers used for diagnosis have limited sensitivity and specificity. Recent research has suggested using blood cell ratios, such as platelet-to-volume ratio (PVR) and platelet-to-lymphocyte ratio (PLR), to improve diagnostic accuracy. The aim of the study was to further validate the effectiveness of PVR and PLR in diagnosing PJI. Methods. A retrospective review was conducted to assess the accuracy of different marker combinations for diagnosing chronic PJI. A total of 573 patients were included in the study, of which 124 knees and 122 hips had a diagnosis of chronic PJI. Complete blood count and synovial fluid analysis were collected. Recently published blood cell ratio cut-off points were applied to receiver operating characteristic curves for all markers and combinations. The area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values were calculated. Results. The results of the analysis showed that the combination of ESR, CRP, synovial white blood cell count (Syn. WBC), and polymorphonuclear neutrophil percentage (PMN%) with PVR had the highest AUC of 0.99 for knees, with sensitivity of 97.73% and specificity of 100%. Similarly, for hips, this combination had an AUC of 0.98, sensitivity of 96.15%, and specificity of 100.00%. Conclusion. This study supports the use of PVR calculated from readily available complete blood counts, combined with established markers, to improve the accuracy in diagnosing chronic PJI in both total hip and knee arthroplasties. Cite this article: Bone Jt Open 2023;4(11):881–888

Aims

Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy.

Aims

The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI.

Aims. To investigate the optimal thresholds and diagnostic efficacy of commonly used serological and synovial fluid detection indexes for diagnosing periprosthetic joint infection (PJI) in patients who have rheumatoid arthritis (RA). Methods. The data from 348 patients who had RA or osteoarthritis (OA) and had previously undergone a total knee (TKA) and/or a total hip arthroplasty (THA) (including RA-PJI: 60 cases, RA-non-PJI: 80 cases; OA-PJI: 104 cases, OA-non-PJI: 104 cases) were retrospectively analyzed. A receiver operating characteristic curve was used to determine the optimal thresholds of the CRP, ESR, synovial fluid white blood cell count (WBC), and polymorphonuclear neutrophil percentage (PMN%) for diagnosing RA-PJI and OA-PJI. The diagnostic efficacy was evaluated by comparing the area under the curve (AUC) of each index and applying the results of the combined index diagnostic test. Results. For PJI prediction, the results of serological and synovial fluid indexes were different between the RA-PJI and OA-PJI groups. The optimal cutoff value of CRP for diagnosing RA-PJI was 12.5 mg/l, ESR was 39 mm/hour, synovial fluid WBC was 3,654/μl, and PMN% was 65.9%; and those of OA-PJI were 8.2 mg/l, 31 mm/hour, 2,673/μl, and 62.0%, respectively. In the RA-PJI group, the specificity (94.4%), positive predictive value (97.1%), and AUC (0.916) of synovial fluid WBC were higher than those of the other indexes. The optimal cutoff values of synovial fluid WBC and PMN% for diagnosing RA-PJI after THA were significantly higher than those of TKA. The specificity and positive predictive value of the combined index were 100%. Conclusion. Serum inflammatory and synovial fluid indexes can be used for diagnosing RA-PJI, for which synovial fluid WBC is the best detection index. Combining multiple detection indexes can provide a reference basis for the early and accurate diagnosis of RA-PJI. Cite this article: Bone Joint Res 2023;12(9):559–570

Aims

The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit.

Aims

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

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.

Aims. 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). Methods. In this retrospective cohort study, 147 consecutive patients with acute or chronic complaints following THA and TKA were included. Diagnosis of PJI was established based on the 2018 International Consensus Meeting criteria. A total of 39 patients diagnosed with PJI (32 chronic and seven acute) and 108 patients with aseptic complications were surgically revised. Results. Using receiver operating characteristic curves and calculating the area under the curve (AUC), an optimal synovial cut-off value of 2,000 PMN/µl was determined (AUC 0.978 (95% confidence interval (CI) 0.946 to 1)). Using this cut-off, sensitivity and specificity of absolute synovial PMN count for PJI were 97.4% (95% CI 91.2 to 100) and 93.5% (95% CI 88.9 to 98.1), respectively. Positive and negative predictive value were 84.4% (95% CI 72.7 to 93.9) and 99.0% (95% CI 96.7 to 100), respectively. Exclusion of 20 patients with acute complications improved specificity to 97.9% (95% CI 94.6 to 100). Different cut-off values for THA (< 3,600 PMN/µl) and TKA (< 2,000 PMN/µl) were identified. Absolute synovial PMN count correlated strongly with synovial alpha-defensin (AD) (r = 0.759; p < 0.001). With a positive AD result, no additional PJI could be identified in any case. Conclusion. Absolute synovial PMN count is a widely available, rapid, cost-effective, and accurate marker in PJI diagnostics, whereas synovial AD appears to be a surrogate parameter of absolute synovial PMN count. Despite limitations in the early postoperative phase, wear, and rheumatic diseases in confirming PJI, an absolute synovial PMN count below 2,000/µl is highly suitable for ruling out PJI, with specific cut-off values for THA and TKA. Cite this article: Bone Joint J 2023;105-B(4):373–381

Aims

CRP is an acute-phase protein that is used as a biomarker to follow severity and progression in infectious and inflammatory diseases. Its pathophysiological mechanisms of action are still poorly defined. CRP in its pentameric form exhibits weak anti-inflammatory activity. The monomeric isoform (mCRP) exerts potent proinflammatory properties in chondrocytes, endothelial cells, and leucocytes. No data exist regarding mCRP effects in human intervertebral disc (IVD) cells. This work aimed to verify the pathophysiological relevance of mCRP in the aetiology and/or progression of IVD degeneration.

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.

Aims. This study aimed to explore the diagnostic value of synovial fluid neutrophil extracellular traps (SF-NETs) in periprosthetic joint infection (PJI) diagnosis, and compare it with that of microbial culture, serum ESR and CRP, synovial white blood cell (WBC) count, and polymorphonuclear neutrophil percentage (PMN%). Methods. In a single health centre, patients with suspected PJI were enrolled from January 2013 to December 2021. The inclusion criteria were: 1) patients who were suspected to have PJI; 2) patients with complete medical records; and 3) patients from whom sufficient synovial fluid was obtained for microbial culture and NET test. Patients who received revision surgeries due to aseptic failure (AF) were selected as controls. Synovial fluid was collected for microbial culture and SF-WBC, SF-PNM%, and SF-NET detection. The receiver operating characteristic curve (ROC) of synovial NET, WBC, PMN%, and area under the curve (AUC) were obtained; the diagnostic efficacies of these diagnostic indexes were calculated and compared. Results. The levels of SF-NETs in the PJI group were significantly higher than those of the AF group. The AUC of SF-NET was 0.971 (95% confidence interval (CI) 0.903 to 0.996), the sensitivity was 93.48% (95% CI 82.10% to 98.63%), the specificity was 96.43% (95% CI 81.65% to 99.91%), the accuracy was 94.60% (95% CI 86.73% to 98.50%), the positive predictive value was 97.73%, and the negative predictive value was 90%. Further analysis showed that SF-NET could improve the diagnosis of culture-negative PJI, patients with PJI who received antibiotic treatment preoperatively, and fungal PJI. Conclusion. SF-NET is a novel and ideal synovial fluid biomarker for PJI diagnosis, which could improve PJI diagnosis greatly. Cite this article: Bone Joint Res 2023;12(2):113–120

Aims

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).

Aims

Degenerative cervical spondylosis (DCS) is a common musculoskeletal disease that encompasses a wide range of progressive degenerative changes and affects all components of the cervical spine. DCS imposes very large social and economic burdens. However, its genetic basis remains elusive.

Aims

This study aimed to explore the role of small colony variants (SCVs) of Staphylococcus aureus in intraosseous invasion and colonization in patients with periprosthetic joint infection (PJI).

Aims. Osteoarthritis (OA) is a common degenerative joint disease worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA. Methods. We used four groups of transcription profiles acquired from the Gene Expression Omnibus database, including articular cartilage, meniscus, synovium, and subchondral bone, to screen differentially expressed genes during OA. Potential crosstalk between tissues was depicted by ligand-receptor pairs. Results. During OA, there were 626, 97, 1,060, and 2,330 differentially expressed genes in articular cartilage, meniscus, synovium, and subchondral bone, respectively. Gene Ontology enrichment revealed that these genes were enriched in extracellular matrix and structure organization, ossification, neutrophil degranulation, and activation at different degrees. Through ligand-receptor pairing and proteome of OA synovial fluid, we predicted ligand-receptor interactions and constructed a crosstalk atlas of the whole joint. Several interactions were reproduced by transwell experiment in chondrocytes and synovial cells, including TNC-NT5E, TNC-SDC4, FN1-ITGA5, and FN1-NT5E. After lipopolysaccharide (LPS) or interleukin (IL)-1β stimulation, the ligand expression of chondrocytes and synovial cells was upregulated, and corresponding receptors of co-culture cells were also upregulated. Conclusion. Each tissue displayed a different expression pattern in transcriptome, demonstrating their specific roles in OA. We highlighted tissue molecular crosstalk through ligand-receptor pairs in OA pathophysiology, and generated a crosstalk atlas. Strategies to interfere with these candidate ligands and receptors may help to discover molecular targets for future OA therapy. Cite this article: Bone Joint Res 2022;11(12):862–872

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

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

Aims

This study evaluated the definitions developed by the European Bone and Joint Infection Society (EBJIS) 2021, the International Consensus Meeting (ICM) 2018, and the Infectious Diseases Society of America (IDSA) 2013, for the diagnosis of periprosthetic joint infection (PJI).

Aims

Staphylococcus aureus is a major cause of septic arthritis, and in vitro studies suggest α haemolysin (Hla) is responsible for chondrocyte death. We used an in vivo murine joint model to compare inoculation with wild type S. aureus 8325-4 with a Hla-deficient strain DU1090 on chondrocyte viability, tissue histology, and joint biomechanics. The aim was to compare the actions of S. aureus Hla alone with those of the animal’s immune response to infection.

Aims

The diagnosis of periprosthetic joint infection (PJI) continues to present a significant clinical challenge. New biomarkers have been proposed to support clinical decision-making; among them, synovial fluid alpha-defensin has gained interest. Current research methodology suggests reference methods are needed to establish solid evidence for use of the test. This prospective study aims to evaluate the diagnostic accuracy of high-performance liquid chromatography coupled with the mass spectrometry (LC-MS) method to detect alpha-defensin in synovial fluid.

Aims

The aim of this study was to evaluate whether, after correction of an adolescent idiopathic scoliosis (AIS), leaving out the subfascial drain gives results that are no worse than using a drain in terms of total blood loss, drop in haemoglobin level, and opioid consumption.

Aims

Osteoarthritis (OA) is a common degenerative joint disease characterized by chronic inflammatory articular cartilage degradation. Long noncoding RNAs (lncRNAs) have been previously indicated to play an important role in inflammation-related diseases. Herein, the current study set out to explore the involvement of lncRNA H19 in OA.

Tendon is a bradytrophic and hypovascular tissue, hence, healing remains a major challenge. The molecular key events involved in successful repair have to be unravelled to develop novel strategies that reduce the risk of unfavourable outcomes such as non-healing, adhesion formation, and scarring. This review will consider the diverse pathophysiological features of tendon-derived cells that lead to failed healing, including misrouted differentiation (e.g. de- or transdifferentiation) and premature cell senescence, as well as the loss of functional progenitors. Many of these features can be attributed to disturbed cell-extracellular matrix (ECM) or unbalanced soluble mediators involving not only resident tendon cells, but also the cross-talk with immigrating immune cell populations. Unrestrained post-traumatic inflammation could hinder successful healing. Pro-angiogenic mediators trigger hypervascularization and lead to persistence of an immature repair tissue, which does not provide sufficient mechano-competence. Tendon repair tissue needs to achieve an ECM composition, structure, strength, and stiffness that resembles the undamaged highly hierarchically ordered tendon ECM. Adequate mechano-sensation and -transduction by tendon cells orchestrate ECM synthesis, stabilization by cross-linking, and remodelling as a prerequisite for the adaptation to the increased mechanical challenges during healing. Lastly, this review will discuss, from the cell biological point of view, possible optimization strategies for augmenting Achilles tendon (AT) healing outcomes, including adapted mechanostimulation and novel approaches by restraining neoangiogenesis, modifying stem cell niche parameters, tissue engineering, the modulation of the inflammatory cells, and the application of stimulatory factors.

Cite this article: Bone Joint Res 2022;11(8):561–574.

Aims

To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction.

Rheumatoid arthritis (RA) is an autoimmune disease that involves T and B cells and their reciprocal immune interactions with proinflammatory cytokines. T cells, an essential part of the immune system, play an important role in RA. T helper 1 (Th1) cells induce interferon-γ (IFN-γ), tumour necrosis factor-α (TNF-α), and interleukin (IL)-2, which are proinflammatory cytokines, leading to cartilage destruction and bone erosion. Th2 cells primarily secrete IL-4, IL-5, and IL-13, which exert anti-inflammatory and anti-osteoclastogenic effects in inflammatory arthritis models. IL-22 secreted by Th17 cells promotes the proliferation of synovial fibroblasts through induction of the chemokine C-C chemokine ligand 2 (CCL2). T follicular helper (Tfh) cells produce IL-21, which is key for B cell stimulation by the C-X-C chemokine receptor 5 (CXCR5) and coexpression with programmed cell death-1 (PD-1) and/or inducible T cell costimulator (ICOS). PD-1 inhibits T cell proliferation and cytokine production. In addition, there are many immunomodulatory agents that promote or inhibit the immunomodulatory role of T helper cells in RA to alleviate disease progression. These findings help to elucidate the aetiology and treatment of RA and point us toward the next steps.

Cite this article: Bone Joint Res 2022;11(7):426–438.

Aims

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

Aims

We aimed to evaluate the utility of ⁶⁸Ga-citrate positron emission tomography (PET)/CT in the differentiation of periprosthetic joint infection (PJI) and aseptic loosening (AL), and compare it with ^99mTc-methylene bisphosphonates (^99mTc-MDP) bone scan.

Aims

Two-stage exchange revision total hip arthroplasty (THA) performed in case of periprosthetic joint infection (PJI) has been considered for many years as being the gold standard for the treatment of chronic infection. However, over the past decade, there have been concerns about its safety and its effectiveness. The purposes of our study were to investigate our practice, collecting the overall spacer complications, and then to analyze their risk factors.

Aims

Bone regeneration during treatment of staphylococcal bone infection is challenging due to the ability of Staphylococcus aureus to invade and persist within osteoblasts. Here, we sought to determine whether the metabolic and extracellular organic matrix formation and mineralization ability of S. aureus-infected human osteoblasts can be restored after rifampicin (RMP) therapy.

This review provides a concise outline of the advances made in the care of patients and to the quality of life after a traumatic spinal cord injury (SCI) over the last century. Despite these improvements reversal of the neurological injury is not yet possible. Instead, current treatment is limited to providing symptomatic relief, avoiding secondary insults and preventing additional sequelae. However, with an ever-advancing technology and deeper understanding of the damaged spinal cord, this appears increasingly conceivable. A brief synopsis of the most prominent challenges facing both clinicians and research scientists in developing functional treatments for a progressively complex injury are presented. Moreover, the multiple mechanisms by which damage propagates many months after the original injury requires a multifaceted approach to ameliorate the human spinal cord. We discuss potential methods to protect the spinal cord from damage, and to manipulate the inherent inhibition of the spinal cord to regeneration and repair. Although acute and chronic SCI share common final pathways resulting in cell death and neurological deficits, the underlying putative mechanisms of chronic SCI and the treatments are not covered in this review.

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.

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.

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.

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.

Aims. The modified Glasgow Prognostic Score (mGPS) uses preoperative CRP and albumin to calculate a score from 0 to 2 (2 being associated with poor outcomes). mGPS is validated in multiple carcinomas. To date, its use in soft-tissue sarcoma (STS) is limited, with only small cohorts reporting that increased mGPS scores correlates with decreased survival in STS patients. Methods. This retrospective multicentre cohort study identified 493 STS patients using clinical databases from six collaborating hospitals in three countries. Centres performed a retrospective data collection for patient demographics, preoperative blood results (CRP and albumin levels and neutrophil, leucocyte, and platelets counts), and oncological outcomes (disease-free survival, local, or metastatic recurrence) with a minimum of two years' follow-up. Results. We found that increased mGPS, tumour size, grade, neutrophil/lymphocyte ratio, and disease recurrence were associated with reduced survival. Importantly, mGPS was the best at stratifying prognosis and could be used in conjunction with tumour grade to sub-stratify patient survival. Conclusion. This study demonstrated that prognosis of localized STS strongly correlates with mGPS, as an increasing score is associated with a poorer outcome. We note that 203 patients (41%) with an STS have evidence of systemic inflammation. We recommend the mGPS and other biochemical blood indicators be introduced into the routine diagnostic assessment in STS patients to stratify patient prognosis. Its use will support clinical decision-making, especially when morbid treatment options such as amputation are being considered. Cite this article: Bone Joint J 2022;104-B(1):168–176

Aims

The aims of this study were to determine the diagnostic yield of image-guided biopsy in providing a final diagnosis in patients with suspected infectious spondylodiscitis, to report the diagnostic accuracy of various microbiological tests and histological examinations in these patients, and to report the epidemiology of infectious spondylodiscitis from a country where tuberculosis (TB) is endemic, including the incidence of drug-resistant TB.

Aims

This study aimed to answer two questions: what are the best diagnostic methods for diagnosing bacterial arthritis of a native joint?; and what are the most commonly used definitions for bacterial arthritis of a native joint?

Aims

Minimally manipulated cells, such as autologous bone marrow concentrates (BMC), have been investigated in orthopaedics as both a primary therapeutic and augmentation to existing restoration procedures. However, the efficacy of BMC in combination with tissue engineering is still unclear. In this study, we aimed to determine whether the addition of BMC to an osteochondral scaffold is safe and can improve the repair of large osteochondral defects when compared to the scaffold alone.

Aims

Monocyte-lymphocyte ratio (MLR) or neutrophil-lymphocyte ratio (NLR) are useful for diagnosing periprosthetic joint infection (PJI), but their diagnostic values are unclear for screening fixation-related infection (FRI) in patients for whom conversion total hip arthroplasty (THA) is planned after failed internal fixation for femoral neck fracture.

Aims

Current guidelines consider analyses of joint aspirates, including leucocyte cell count (LC) and polymorphonuclear percentage (PMN%) as a diagnostic mainstay of periprosthetic joint infection (PJI). It is unclear if these parameters are subject to a certain degree of variability over time. Therefore, the aim of this study was to evaluate the variation of LC and PMN% in patients with aseptic revision total knee arthroplasty (TKA).

Aims. Histology is an established tool in diagnosing periprosthetic joint infections (PJIs). Different thresholds, using various infection definitions and histopathological criteria, have been described. This study determined the performance of different thresholds of polymorphonuclear neutrophils (≥ 5 PMN/HPF, ≥ 10 PMN/HPF, ≥ 23 PMN/10 HPF) , when using the European Bone and Joint Infection Society (EBJIS), Infectious Diseases Society of America (IDSA), and the International Consensus Meeting (ICM) 2018 criteria for PJI. Methods. A total of 119 patients undergoing revision total hip (rTHA) or knee arthroplasty (rTKA) were included. Permanent histology sections of periprosthetic tissue were evaluated under high power (400× magnification) and neutrophils were counted per HPF. The mean neutrophil count in ten HPFs was calculated (PMN/HPF). Based on receiver operating characteristic (ROC) curve analysis and the z-test, thresholds were compared. Results. Using the EBJIS criteria, a cut-off of ≥ five PMN/HPF showed a sensitivity of 93% (95% confidence interval (CI) 81 to 98) and specificity of 84% (95% CI 74 to 91). The optimal threshold when applying the IDSA and ICM criteria was ≥ ten PMN/HPF with sensitivities of 94% (95% CI 79 to 99) and 90% (95% CI 76 to 97), and specificities of 86% (95% CI 77 to 92) and 92% (95% CI 84 to 97), respectively. In rTKA, a better performance of histopathological analysis was observed in comparison with rTHA when using the IDSA criteria (p < 0.001). Conclusion. With high accuracy, histopathological analysis can be supported as a confirmatory criterion in diagnosing periprosthetic joint infections. A threshold of ≥ five PMN/HPF can be recommended to distinguish between septic and aseptic loosening, with an increased possibility of detecting more infections caused by low-virulence organisms. However, neutrophil counts between one and five should be considered suggestive of infection and interpreted carefully in conjunction with other diagnostic test methods. Cite this article: Bone Joint Res 2021;10(8):536–547

Aims

Poly (ADP-ribose) polymerase (PARP) inhibitor has been reported to attenuate inflammatory response in rat models of inflammation. This study was designed to investigate the effect of PARP signalling in osteoarthritis (OA) cartilage inflammatory response in an OA rat model.

Aims

Dual mobility implants in total hip arthroplasty are designed to increase the functional head size, thus decreasing the potential for dislocation. Modular dual mobility (MDM) implants incorporate a metal liner (e.g. cobalt-chromium alloy) in a metal shell (e.g. titanium alloy), raising concern for mechanically assisted crevice corrosion at the modular liner-shell connection. We sought to examine fretting and corrosion on MDM liners, to analyze the corrosion products, and to examine histologically the periprosthetic tissues.

Aims. Aseptic loosening is a leading cause of uncemented arthroplasty failure, often accompanied by fibrotic tissue at the bone-implant interface. A biological target, neutrophil extracellular traps (NETs), was investigated as a crucial connection between the innate immune system’s response to injury, fibrotic tissue development, and proper bone healing. Prevalence of NETs in peri-implant fibrotic tissue from aseptic loosening patients was assessed. A murine model of osseointegration failure was used to test the hypothesis that inhibition (through Pad4-/- mice that display defects in peptidyl arginine deiminase 4 (PAD4), an essential protein required for NETs) or resolution (via DNase 1 treatment, an enzyme that degrades the cytotoxic DNA matrix) of NETs can prevent osseointegration failure and formation of peri-implant fibrotic tissue. Methods. Patient peri-implant fibrotic tissue was analyzed for NETs biomarkers. To enhance osseointegration in loose implant conditions, an innate immune system pathway (NETs) was either inhibited (Pad4-/- mice) or resolved with a pharmacological agent (DNase 1) in a murine model of osseointegration failure. Results. NETs biomarkers were identified in peri-implant fibrotic tissue collected from aseptic loosening patients and at the bone-implant interface in a murine model of osseointegration failure. Inhibition (Pad4-/-) or resolution (DNase 1) of NETs improved osseointegration and reduced fibrotic tissue despite loose implant conditions in mice. Conclusion. This study identifies a biological target (NETs) for potential noninvasive treatments of aseptic loosening by discovering a novel connection between the innate immune system and post-injury bone remodelling caused by implant loosening. By inhibiting or resolving NETs in an osseointegration failure murine model, fibrotic tissue encapsulation around an implant is reduced and osseointegration is enhanced, despite loose implant conditions. Cite this article: Bone Joint J 2021;103-B(7 Supple B):135–144

Aims

The STRYDE nail is an evolution of the PRECICE Intramedullary Limb Lengthening System, with unique features regarding its composition. It is designed for load bearing throughout treatment in order to improve patient experience and outcomes and allow for simultaneous bilateral lower limb lengthening. The literature published to date is limited regarding outcomes and potential problems. We report on our early experience and raise awareness for the potential of adverse effects from this device.

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

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.

Aims. 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. Methods. Patients undergoing joint aspiration for evaluation of pain after total knee arthroplasty (TKA) or total hip arthroplasty (THA) were considered for inclusion. Synovial fluids from 99 patients (25 THA and 74 TKA) were analyzed by WBC count and PMN% analysis, AD LFA, and AD ELISA. WBC and PMN% cutoffs of ≥ 1,700 cells/mm. 3. and ≥ 65% for TKA and ≥ 3,000 cells/mm. 3. and ≥ 80% for THA were used, respectively. A panel of three physicians, all with expertise in orthopaedic infections and who were blinded to the results of AD tests, independently reviewed patient data to diagnose subjects as with or without PJI. Consensus PJI classification was used as the reference standard to evaluate test performances. Results were compared using McNemar’s test and area under the receiver operating characteristic curve (AUC) analysis. Results. Expert consensus classified 18 arthroplasies as having failed due to PJI and 81 due to aseptic failure. Using these classifications, the calculated sensitivity and specificity of AD LFA was 83.3% (95% confidence interval (CI) 58.6 to 96.4) and 93.8% (95% CI 86.2 to 98.0), respectively. Sensitivity and specificity of AD ELISA was 83.3% (95% CI 58.6 to 96.4) and 96.3% (95% CI 89.6 to 99.2), respectively. There was no statistically significant difference between sensitivity (p = 1.000) or specificity (p = 0.157) of the two AD assays. AUC for AD LFA was 0.891. In comparison, AUC for synovial WBC count, PMN%, and the combination of the two values was 0.821 (sensitivity p = 1.000, specificity p < 0.001), 0.886 (sensitivity p = 0.317, specificity p = 0.011), and 0.926 (sensitivity p = 0.317, specificity p = 0.317), respectively. Conclusion. The diagnostic accuracy of synovial AD for PJI diagnosis is comparable and not statistically superior to that of synovial WBC count plus PMN% combined. Cite this article: Bone Joint J 2021;103-B(6):1119–1126

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.

Aims

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.

Aims

Periprosthetic joint infections (PJIs) are among the most devastating complications after joint arthroplasty. There is limited evidence on the efficacy of different antiseptic solutions on reducing biofilm burden. The purpose of the present study was to test the efficacy of different antiseptic solutions against clinically relevant microorganisms in biofilm.

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.

Periprosthetic joint infection (PJI) is one of the most dreaded complications after arthroplasty surgery; thus numerous approaches have been undertaken to equip metal surfaces with antibacterial properties. Due to its antimicrobial effects, silver is a promising coating for metallic surfaces, and several types of silver-coated arthroplasty implants are in clinical use today. However, silver can also exert toxic effects on eukaryotic cells both in the immediate vicinity of the coated implants and systemically. In most clinically-used implants, silver coatings are applied on bulk components that are not in direct contact with bone, such as in partial or total long bone arthroplasties used in tumour or complex revision surgery. These implants differ considerably in the coating method, total silver content, and silver release rates. Safety issues, such as the occurrence of argyria, have been a cause for concern, and the efficacy of silver coatings in terms of preventing PJI is also controversial. The application of silver coatings is uncommon on parts of implants intended for cementless fixation in host bone, but this option might be highly desirable since the modification of implant surfaces in order to improve osteoconductivity can also increase bacterial adhesion. Therefore, an optimal silver content that inhibits bacterial colonization while maintaining osteoconductivity is crucial if silver were to be applied as a coating on parts intended for bone contact. This review summarizes the different methods used to apply silver coatings to arthroplasty components, with a focus on the amount and duration of silver release from the different coatings; the available experience with silver-coated implants that are in clinical use today; and future strategies to balance the effects of silver on bacteria and eukaryotic cells, and to develop silver-coated titanium components suitable for bone ingrowth.

Cite this article: Bone Joint J 2021;103-B(3):423–429.

Aims

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.

Aims

Periprosthetic joint infections (PJIs) and osteomyelitis are clinical challenges that are difficult to eradicate. Well-characterized large animal models necessary for testing and validating new treatment strategies for these conditions are lacking. The purpose of this study was to develop a rabbit model of chronic PJI in the distal femur.

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.

Aims

Microbiological culture is a key element in the diagnosis of periprosthetic joint infection (PJI). However, cultures of periprosthetic tissue do not have optimal sensitivity. One of the main reasons for this is that microorganisms are not released from the tissues, either due to biofilm formation or intracellular persistence. This study aimed to optimize tissue pretreatment methods in order to improve detection of microorganisms.

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.

Aims. 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. Methods. We included 50 synovial fluid samples from patients with (n = 25) and without (n = 25) confirmed PJI from an institutional tissue bank collected between May 2015 and December 2016. We also included 22 synovial fluid samples aspirated from patients with active IJD presenting to Department of Rheumatology, the first Medical Centre, Chinese PLA General Hospital. Concentrations of the ten candidate biomarkers were measured in the synovial fluid samples using standard enzyme-linked immunosorbent assays (ELISA). The diagnostic accuracy was evaluated by receiver operating characteristic (ROC) curves. Results. BPI, LTF, NGAL, ELA-2, and α-defensin were well-performing biomarkers for detecting PJI, with areas under the curve (AUCs) of 1.000 (95% confidence interval, 1.000 to 1.000), 1.000 (1.000 to 1.000), 1.000 (1.000 to 1.000), 1.000 (1.000 to 1.000), and 0.998 (0.994 to 1.000), respectively. The other markers (LL-37, HBD-2, D-dimer, PCT, and HBD-3) had limited diagnostic value. For the five well-performing biomarkers, elevated concentrations were observed in patients with active IJD. The original best thresholds determined by the Youden index, which discriminated PJI cases from non-PJI cases could not discriminate PJI cases from active IJD cases, while elevated thresholds resulted in good performance. Conclusion. BPI, LTF, NGAL, ELA-2, and α-defensin demonstrated excellent performance for diagnosing PJI. However, all five markers showed elevated concentrations in patients with IJD activity. For patients with IJD, elevated thresholds should be considered to accurately diagnose PJI. Cite this article: Bone Joint J 2021;103-B(1):32–38

Aims. 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). Methods. Blood and synovial fluid samples were collected prospectively from 195 patients undergoing primary or revision hip and knee arthroplasty. Patients were divided into five groups: 1) primary total hip and knee arthroplasty performed due to idiopathic osteoarthritis (OA; n = 60); 2) revision hip and knee arthroplasty performed due to aseptic failure of the implant (AR-TJR; n = 40); 3) patients with a confirmed diagnosis of chronic PJI awaiting surgery (n = 45); 4) patients who have finished the first stage of the PJI treatment with the use of cemented spacer and were qualified for replantation procedure (SR-TJR; n = 25), and 5) patients with rheumatoid arthritis undergoing primary total hip and knee arthroplasty (RA; n = 25). CLP concentrations were measured quantitatively in the blood and synovial fluid using an immunoturbidimetric assay. Additionally, blood and synovial CRP, blood interleukin-6 (IL-6), and ESR were measured, and a leucocyte esterase (LE) strip test was performed. Results. Patients with PJI had higher CLP concentrations than those undergoing aseptic revision in blood (median PJI 2.14 mg/l (interquartile range (IQR) 1.37 to 3.56) vs AR-TJR 0.66 mg/l (IQR 0.3 to 0.83); p < 0.001) and synovial fluid samples (median PJI 20.46 mg/l (IQR 14.3 to 22.36) vs AR-TJR 0.7 mg/l (IQR 0.41 to 0.95); p < 0.001). With a cut-off value of 1.0 mg/l, blood CLP showed a sensitivity, specificity, positive predictive value, and negative predictive value of 93.3%, 87.5%, 89.4%, and 92.1%, respectively. For synovial fluid with a cut-off value of 1.5 mg/l, these were 95.6%, 95%, 95.5%, and 95%, respectively. Conclusion. This small study suggests that synovial and blood CLP are useful markers in chronic PJI diagnosis with similar or higher sensitivity and specificity than routinely used markers such as CRP, ESR, IL-6, and LE. CLP was not useful to differentiate patients with PJI from those with rheumatoid arthritis. Cite this article: Bone Joint J 2021;103-B(1):46–55

Aims

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.

Aims

The primary aim of this study was to compare the postoperative systemic inflammatory response in conventional jig-based total knee arthroplasty (conventional TKA) versus robotic-arm assisted total knee arthroplasty (robotic TKA). Secondary aims were to compare the macroscopic soft tissue injury, femoral and tibial bone trauma, localized thermal response, and the accuracy of component positioning between the two treatment groups.

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.

Aims

There is a lack of evidence about the risk factors for local recurrence of a giant cell tumour (GCT) of the sacrum treated with nerve-sparing surgery, probably because of the rarity of the disease. This study aimed to answer two questions: first, what is the rate of local recurrence of sacral GCT treated with nerve-sparing surgery and second, what are the risk factors for its local recurrence?

Aims

The primary aim was to assess the independent influence of coronavirus disease (COVID-19) on 30-day mortality for patients with a hip fracture. The secondary aims were to determine whether: 1) there were clinical predictors of COVID-19 status; and 2) whether social lockdown influenced the incidence and epidemiology of hip fractures.

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

Aims

This study aimed to evaluate calprotectin in synovial fluid for diagnosing chronic prosthetic joint infection (PJI) .

Aims

The first death in the UK caused by COVID-19 occurred on 5 March 2020. We aim to describe the clinical characteristics and outcomes of major trauma and orthopaedic patients admitted in the early COVID-19 era.

Aims

CERAMENT|G is an absorbable gentamicin-loaded biocomposite used as an on-site vehicle of antimicrobials for the treatment of chronic osteomyelitis. The purpose of the present study was to investigate the sole effect of CERAMENT|G, i.e. without additional systemic antimicrobial therapy, in relation to a limited or extensive debridement of osteomyelitis lesions in a porcine model.

A balanced inflammatory response is important for successful fracture healing. The response of osteoporotic fracture healing is deranged and an altered inflammatory response can be one underlying cause. The objectives of this review were to compare the inflammatory responses between normal and osteoporotic fractures and to examine the potential effects on different healing outcomes. A systematic literature search was conducted with relevant keywords in PubMed, Embase, and Web of Science independently. Original preclinical studies and clinical studies involving the investigation of inflammatory response in fracture healing in ovariectomized (OVX) animals or osteoporotic/elderly patients with available full text and written in English were included. In total, 14 articles were selected. Various inflammatory factors were reported; of those tumour necrosis factor-α (TNF-α) and interleukin (IL)-6 are two commonly studied markers. Preclinical studies showed that OVX animals generally demonstrated higher systemic inflammatory response and poorer healing outcomes compared to normal controls (SHAM). However, it is inconclusive if the local inflammatory response is higher or lower in OVX animals. As for clinical studies, they mainly examine the temporal changes of the inflammatory stage or perform comparison between osteoporotic/fragility fracture patients and normal subjects without fracture. Our review of these studies emphasizes the lack of understanding that inflammation plays in the altered fracture healing response of osteoporotic/elderly patients. Taken together, it is clear that additional studies, preclinical and clinical, are required to dissect the regulatory role of inflammatory response in osteoporotic fracture healing.

Cite this article: Bone Joint Res 2020;9(7):368–385.

Aims

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

Aims. 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. Methods. A cohort of 106 patients having surgery for suspected septic nonunion after failed fracture fixation were studied. Blood samples were collected preoperatively, and the concentration of serum CRP, WBC, and differential cell count were analyzed. The areas under the curve (AUCs) of diagnostic tests were compared using the z-test. Regression trees were constructed and internally cross-validated to derive a simple diagnostic decision tree. Results. Using the FRI consensus definition, 46 patients (43%) were identified as infected. Sensitivity, specificity, and AUC of CRP were 67% (95% confidence interval (CI) 52% to 80%), 61% (95% CI 47% to 74%), and 0.64 (95% CI 0.54 to 0.74); of WBC count were 17% (95% CI 9% to 31%), 95% (95% CI 86% to 99%), and 0.57 (95% CI 0.50 to 0.62); of %N 13% (95% CI 6% to 26%), 87% (95% CI 76% to 93%), and 0.50 (95% CI 0.43 to 0.56); and of NLR 28% (95% CI 17% to 43%), 80% (95% CI 68% to 88%), and 0.54 (95% CI 0.46 to 0.63), respectively. A better performance of serum CRP was shown in comparison to the leucocyte count (p = 0.006), %N (p < 0.001), and NLR (p = 0.001). A statistically lower serum CRP level was shown in patients with an infection caused by a low virulence microorganism in comparison to high virulence bacteria (p = 0.008). We found that a simple decision tree approach using only low serum neutrophils (< 3.615 × 10. 9. /l) and low CRP (< 2.45 mg/l) may allow better identification of aseptic cases. Conclusion. The evaluated serum inflammatory markers showed limited diagnostic value in the preoperative diagnosis of FRI when using the uniform FRI Consensus Definition. Therefore, they should remain as suggestive criteria in diagnosing FRI. Although CRP showed a higher performance in comparison to the other serum markers, it is insufficiently accurate to diagnose a septic nonunion, especially when caused by low virulence microorganisms. Cite this article: Bone Joint J 2020;102-B(7):904–911

Aims

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

Aims

Sickle cell disease (SCD) is an autosomal recessive inherited condition that presents with a number of clinical manifestations that include musculoskeletal manifestations (MM). MM may present differently in different individuals and settings and the predictors are not well known. Herein, we aimed at determining the predictors of MM in patients with SCD at the University Teaching Hospital, Lusaka, Zambia.

Aims

Arthrofibrosis is a relatively common complication after joint injuries and surgery, particularly in the knee. The present study used a previously described and validated rabbit model to assess the biomechanical, histopathological, and molecular effects of the mast cell stabilizer ketotifen on surgically induced knee joint contractures in female rabbits.

Aims

Preoperative diagnosis is important for revision surgery after prosthetic joint infection (PJI). The purpose of our study was to determine whether reverse transcription-quantitative polymerase chain reaction (RT-qPCR), which is used to detect bacterial ribosomal RNA (rRNA) preoperatively, can reveal PJI in low volumes of aspirated fluid.

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).

Aims

This pilot study tested the performance of a rapid assay for diagnosing prosthetic joint infection (PJI), which measures synovial fluid calprotectin from total hip and knee revision patients.

Aims

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