Elevated synovial leukocyte count is a minor criterion derived from the musculoskeletal infection society (MSIS) widely used in clinical practice for diagnosis of prosthetic joint infection. There is evidence to suggest analysis within 1 hour, preferentially within 30 minutes, of aspiration reduces the risk of ex vivo cell lysis occurring during prolonged transport. Multiple site working is more common practice and the availability of a lab on site to perform these tests is not always possible. We aimed to assess whether we could safely perform synovial leukocyte counts within our cold site in the diagnosis of prosthetic joint infection. We reviewed all orthopaedic synovial fluid aspirates within the lower limb arthroplasty unit from April 2021 – April 2022 performed at South Tees NHS Foundation Trust. We assessed time from aspirate to the lab using electronic data resources. This information was compared with the labs ability to perform a synovial leukocyte count to determine the impact of delays on testing. 110 patients (34.5% hips and 63.6% knees) were identified between two sites. Time from aspirate to lab ranged from 0 mins to 26 hrs 34 mins. Mean time to processing was 3hrs 10 mins. 50% of all samples had a synovial leukocyte count performed. 67% of patients had a cell differential performed. There was no difference in the ability to perform a synovial leukocyte count between samples process in < 2hours vs > 6 hours. We conclude that it is safe practice to perform joint aspirates for the work up of periprosthetic joint infections in sites where no laboratory is immediately available as the delay to processing synovial fluid does not alter the ability to perform a synovial leukocyte count. This study will provide evidence to enable the work up of periprosthetic joint infections in cold centres and therefore reduce the delay in diagnosis and proceeding management

Aims. The aim of this study was to evaluate blood metal ion levels, leucocyte profiles, and serum cytokines in patients with a total hip arthroplasty (THA) involving modular dual-mobility components. Patients and Methods. A total of 39 patients were recruited, with clinical follow-up of up to two years. Outcome was assessed using the Harris Hip Score (HHS, the 12-Item Short-Form Health Survey (SF-12), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and a visual analogue scale (VAS) for pain. Blood concentrations of cobalt (Co), chromium (Cr), and serum cytokines were measured. Subpopulations of leucocytes were analyzed by flow cytometry. Results. The clinical performance was good. Blood Co levels (ref 1.0 µg/l) were mildly elevated in seven patients at three months, and two patients at two years’ follow-up. The preoperative Cr levels were normal except for one patient with a detectable Cr (1.2 µg/l). Cr levels were detectable in three patients at three months, two patients at one year, and three patients at two years’ follow-up. No patients had symptoms suggestive of failure. Although flow cytometry showed constant circulating leucocyte profiles, there was a significant reduction of serum interleukin (IL)-4, IL-5, and interferon gamma (IFNγ) postoperatively compared with the preoperative levels (p < 0.05). Conclusion. These results suggest that THA using modular dual-mobility components is safe. This allows an opportunity to use a large femoral head and a thick polyethylene bearing surface, which is especially useful in revision procedures or high-risk situations when added stability is required. Cite this article: Bone Joint J 2019;101-B:1035–1041

No single test has demonstrated absolute accuracy in the diagnosis of periprosthetic joint infection (PJI). Leukocyte esterase (LE) is a synovial marker that has proven utility in the diagnosis of PJI. The purpose of this prospective study was to (1) identify the optimal cutoff for the use of LE in the diagnosis of PJI and (2) determine whether performance of the LE strip test varied by infecting organism. This prospective study enrolled 1,015 patients undergoing hip or knee revision arthroplasty at a single institution from 2009 to September 2021. PJI was defined using a modified version of 2018 International Consensus Meeting (ICM) criteria that excluded LE when calculating the ICM score. Receiver operating characteristic curves were used to assess the utility of the LE strip test in the diagnosis of PJI. 973 patients were included in the analyses. 246 (25.4%) were classified as ICM-positive and 727 (74.6%) were classified as ICM-negative. An LE cutoff of “1+” (AUC 0.819, sensitivity 73.2%, specificity 90.6%) had superior accuracy to an LE cutoff of “2+” (AUC 0.713, sensitivity 43.9%, specificity 98.8%) in the overall diagnosis of PJI (p<0.001). When stratifying by organism type, an LE cutoff of “1+” had the best diagnostic utility for PJI caused by methicillin resistant Staphylococcus aureus (AUC 0.888, sensitivity 87.0%, n=23) followed by Streptococcus spp. (AUC 0.882, sensitivity 85.7%, n=28), coagulase negative Staphylococci (AUC 0.836, sensitivity 76.6%, n=47), methicillin sensitive Staphylococcus aureus (AUC 0.806, sensitivity 70.6%, n=34), culture negative (AUC 0.793, sensitivity 67.9%, n=56), and gram negative rods (AUC 0.763, sensitivity 61.9%, n=21). To our knowledge, this is the largest study evaluating the utility of the LE strip test in the diagnosis of PJI. Based on our findings, it appears that a “1+” cutoff has higher diagnostic utility than a cutoff of “2+”

Aims. Leucocyte esterase (LE) has been shown to be an accurate marker of prosthetic joint infection (PJI), and has been proposed as an alternative to frozen section (FS) histology for intraoperative diagnosis. In this study, the intraoperative assessment of LE was compared with FS histology for the diagnosis of prosthetic hip infection. Patients and Methods. A total of 119 patients undergoing revision total hip arthroplasty (THA) between June 2015 and December 2017 were included in the study. There were 56 men and 63 women with a mean age of 66.2 years (27 to 88). Synovial fluid was collected before arthrotomy for the assessment of LE using enzymatic colourimetric strips. Between five and six samples were stained with haematoxylin and eosin for FS histology, and considered suggestive of infection when at least five polymorphonuclear leucocytes were found in five high-power fields. Results. The sensitivity and specificity of the LE assay were 100% and 93.8%, respectively; the positive (PPV) and the negative (NPV) predictive values were 79.3% and 100%, respectively. The mean time between the collection of the sample and the result being known was 20.1 minutes (. sd. 4.4). The sensitivity and specificity of FS histology were 78.3% and 96.9%, respectively; the PPV and the NPV were 85.7% and 94.9%, respectively. The mean time between the collection of the sample and the result being known was 27.2 minutes (. sd. 6.9). Conclusion. The sensitivity of LE assay was higher, with similar specificity and diagnostic accuracy, compared with FS histology. The faster turnaround time, its ease of use, and low costs make LE assay a valuable alternative to FS histology. We now use it routinely for the intraoperative diagnosis of PJI. Cite this article: Bone Joint J 2019;101-B:372–377

Leukocyte esterase (LE) has shown to be an accurate marker of prosthetic joint infections and has been proposed as an alternative to frozen section (FS) for intra-operative diagnosis. In this study, intra-operative determination of LE was compared with FS for the diagnosis of periprosthetic hip infections. One hundred and nineteen patients undergoing hip revision surgery due to prosthetic joint failure from June 2015 to December 2017 were considered. Joint fluids were collected before the arthrotomy for determination of LE which was performed by using enzymatic colorimetric strips. Four to six samples were stained with hematoxylin eosin for FS and considered suggestive for infection when at least 5 polymorphonuclear leukocytes in 5 fields at high power fields were found. Sensitivity and specificity of LE were 100% and 93.8 %, respectively. The positive predictive value was 79.3 %, while the negative predictive value was 100%. Time from collection to response was 20.1 ± 4.4 minutes. Sensitivity and specificity of FS were 83.3 % and 92.1 %, respectively. The positive and negative predictive values were 84.6 % and 97.1%. Time from sample collection response was 27.2 ± 6.9 minutes. LE showed a higher sensitivity and a slightly lower specificity and the same diagnostic accuracy of intraoperative FS. The faster turnaround time (about 20 minutes from receiving of sample by the laboratory), its ease of use and the low costs make this test a valuable alternative to frozen sections and is going to replace FS in our clinical practice

Aims. Hip resurfacing remains a potentially valuable surgical procedure for appropriately-selected patients with optimised implant choices. However, concern regarding high early failure rates continues to undermine confidence in use. A large contributor to failure is adverse local tissue reactions around metal-on-metal (MoM) bearing surfaces. Such phenomena have been well-explored around MoM total hip arthroplasties, but comparable data in equivalent hip resurfacing procedures is lacking. In order to define genetic predisposition, we performed a case-control study investigating the role of human leucocyte antigen (HLA) genotype in the development of pseudotumours around MoM hip resurfacings. Methods. A matched case-control study was performed using the prospectively-collected database at the host institution. In all, 16 MoM hip resurfacing 'cases' were identified as having symptomatic periprosthetic pseudotumours on preoperative metal artefact reduction sequence (MARS) MRI, and were subsequently histologically confirmed as high-grade aseptic lymphocyte-dominated vasculitis-associated lesions (ALVALs) at revision surgery. ‘Controls’ were matched by implant type in the absence of evidence of pseudotumour. Blood samples from all cases and controls were collected prospectively for high resolution genetic a nalysis targeting 11 separate HLA loci. Statistical significance was set at 0.10 a priori to determine the association between HLA genotype and pseudotumour formation, given the small sample size. Results. Using a previously-reported ALVAL classification, the majority of pseudotumour-positive caseswere found to have intermediate-grade group 2 (n = 10; 63%) or group 3 (n = 4; 25%) histological findings. Two further patients (13%) had high-grade group 4 lesions. HLA-DQB1*05:03:01 (p = 0.0676) and HLA-DRB1*14:54:01 (p = 0.0676) alleles were significantly associated with a higher risk of pseudotumour formation, while HLA-DQA1*03:01:01 (p = 0.0240), HLA-DRB1*04:04:01 (p = 0.0453), HLA-C*01:02:01 (p = 0.0453), and HLA-B*27:05:02 (p = 0.0855) were noted to confer risk reduction. Conclusion. These findings confirm the association between specific HLA genotypes and the risk of pseudotumour development around MoM hip resurfacings. Specifically, the two ‘at risk’ alleles (DQB1*05:03:01 and DRB1*14:54:01) may hold clinical value in preoperative screening and prospective surgical decision-making. Cite this article: Bone Jt Open 2023;4(3):182–187

In a recent phase 2 superiority clinical trial we demonstrated that a single dose of 60mg of the human monoclonal antibody denosumab inhibits osteolytic lesion activity in patients undergoing revision total hip arthroplasty (THA), demonstrating proof of biological efficacy for this clinical application. Here, we examined the effect that denosumab has on disease biology at the osteolysis tissue level. Osteolytic tissue taken from the prosthesis-bone lesion interface at revision surgery in patients with osteolysis (n=10 participants that had received a single 60 mg dose of denosumab 8 weeks prior to revision surgery and n=10 that had received placebo) was examined for total genetic message activity and protein levels using whole genome sequencing and mass spectrometry, respectively. The top five upregulated enriched pathways with denosumab treatment included inflammatory response, myeloid cell activation, myeloid leukocyte migration, neutrophil and granulocyte activation (p<6.26 × 10. −28. ). Cell morphogenesis was amongst the most downregulated pathways (p<3.42 ×10. −23. ). Finally, comparison of the trial mRNA and protein data versus mouse single cell RNA sequencing data of the same pathway blockade in mouse tibia showed the same direction of effect, suggesting that giving the drug causes then cells responsible for osteolysis to disperse into a more immature form (128 of 189 genes (z=4.87, P<0.0001) disease and functional pathways at the mRNA level and 10 of 11 (z=2.72, P=0.0065) at the protein level). In this first-in-man study we identify multiple genes and pathways within periprosthetic osteolysis tissue that are affected by denosumab treatment. The dominant pathways involved upregulation of innate inflammatory signaling and downregulation of cell morphogenesis. We also found enrichment of similar disease and functional pathways at both the mRNA and protein levels versus mRNA pathway enrichment found in mouse osteomorphs. These data provide the first human data of the mechanistic effect of denosumab treatment on inflammatory osteolytic lesion activity after joint replacement that is necessary to support its clinical application. ∗Winner of The Bone & Joint Journal prize∗

Cutibacterium species (formerly Propionibacterium species) are increasingly recognized as causative pathogens of low-grade periprosthetic joint infections (PJI). The clinical manifestation of infections caused by this low virulent microorganism is nonspecific and the interpretation remains challenging. In this prospective cohort study from 01/2012 to 07/2017 we analyzed the clinical and diagnostic characteristics of microbiologically proven hip PJI caused by Cutibacterium species. PJI was defined by growth of Cutibacteria in ≥2 periprosthetic tissue samples or in sonication fluid of the removed implant (>50 CFU/ml) at revision surgery. If Cutibacteria grew only in synovial fluid at least one other positive microbiological specimen or non-microbiological criterion was required. We included 26 patients suffering from Cutibacterium hip PJI, among them 19 were males (73%). The majority of PJI (24, 92%) presented delayed (3–24 months) or late (>24 months) after implantation. Sinus tract was present in 4 patients (16%) and radiological implant loosening in 16 patients (62%). Among non-microbiological diagnostic tests, increased synovial fluid leukocyte count showed the highest sensitivity (82%), followed by tissue histology (71%) and serum C-reactive protein (58%). After 7 days of incubation Cutibacterium grew in synovial fluid, periprosthetic tissue and sonication fluid culture in 20%, 42% and 32%, respectively, and in 43%, 76% and 83%, respectively, after 14 days of incubation. We conclude that Cutibacterium PJI was diagnosed late in the disease course and presented with subtle clinical signs. Prolonged culture incubation and implant sonication improved the poor performance of conventional microbiological tests. Due to lack of reliable diagnostic tests, Cutibacterium remains difficult to detect making the diagnosis challenging

Abnormal wear of cobalt-containing metal-on-metal joints is associated with inflammatory pseudotumours. Cobalt ions activate human toll-like receptor 4 (TLR4), which normally responds to bacterial lipopolysaccharide (LPS) in sepsis. Activation of TLR4 by LPS increases the expression of chemokines IL-8 and CXCL10, which recruit leukocytes and activated T-cells, respectively. This study was designed to determine whether cobalt induces a similar inflammatory response to LPS by promoting the expression of IL-8 and CXCL10. A human monocytic cell line, derived from acute monocytic leukaemia, was treated with cobalt ions and expression of IL-8 and CXCL10 measured at mRNA and protein levels. Cobalt-treated macrophages showed a 60-fold increase in IL-8 mRNA, and an eightfold increase in production of the mature chemokine (both p < 0.001); expression of the CXCL10 gene and protein was also significantly increased by cobalt (both p < 0.001). Experiments were also performed in the presence of CLI-095, a TLR4-specific antagonist which abrogated the cobalt-mediated increase in IL-8 and CXCL10 expression. . These findings suggest that cobalt ions induce inflammation similar to that observed during sepsis by the simultaneous activation of two TLR4-mediated signalling pathways. These pathways result in increased production of IL-8 and CXCL10, and may be implicated in pseudotumour formation following metal-on-metal replacement. Cite this article: Bone Joint J 2014; 96-B:1172–7

Aims

Current diagnostic tools are not always able to effectively identify periprosthetic joint infections (PJIs). Recent studies suggest that circulating microRNAs (miRNAs) undergo changes under pathological conditions such as infection. The aim of this study was to analyze miRNA expression in hip arthroplasty PJI patients.

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

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The aim of the HIPGEN consortium is to develop the first cell therapy product for hip fracture patients using PLacental-eXpanded (PLX-PAD) stromal cells.

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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.

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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.

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

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There is a paucity of long-term studies analyzing risk factors for failure after single-stage revision for periprosthetic joint infection (PJI) following total hip arthroplasty (THA). We report the mid- to long-term septic and non-septic failure rate of single-stage revision for PJI after THA.

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We aimed to report the mid- to long-term rates of septic and aseptic failure after two-stage revision surgery for periprosthetic joint infection (PJI) following total hip arthroplasty (THA).

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

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Prosthetic joint infection (PJI) and aseptic loosening in total hip arthroplasty (THA) can present with pain and osteolysis. The Musculoskeletal Infection Society (MSIS) has provided criteria for the diagnosis of PJI. The aim of our study was to analyze the utility of F18-fluorodeoxyglucose (FDG) positron emission tomography (PET) CT scan in the preoperative diagnosis of septic loosening in THA, based on the current MSIS definition of prosthetic joint infection.

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