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). Methods. We conducted a prospective, double-centre study of 40 patients with 40 knee joints. Patients underwent joint aspiration at two different time points with a maximum period of 120 days in between these interventions and without any events such as other joint aspirations or surgeries. The main indications for TKA revision surgery were aseptic implant loosening (n = 24) and joint instability (n = 11). Results. Overall, 80 synovial fluid samples of 40 patients were analyzed. The average time period between the joint aspirations was 50 days (SD 32). There was a significantly higher percentage change in LC when compared to PMN% (44.1% (SD 28.6%) vs 27.3% (SD 23.7%); p = 0.003). When applying standard definition criteria, LC counts were found to skip back and forth between the two time points with exceeding the thresholds in up to 20% of cases, which was significantly more compared to PMN% for the European Bone and Joint Infection Society (EBJIS) criteria (p = 0.001), as well as for Musculoskeletal Infection Society (MSIS) (p = 0.029). Conclusion. LC and PMN% are subject to considerable variation. According to its higher interindividual variance, LC evaluation might contribute to false-positive or false-negative results in PJI assessment. Single LC testing prior to TKA revision surgery seems to be insufficient to exclude PJI. On the basis of the obtained results, PMN% analyses overrule LC measurements with regard to a conclusive diagnostic algorithm. Cite this article: Bone Jt Open 2021;2(8):566–572

Aims. To verify whether secretory leucocyte protease inhibitor (SLPI) can promote early tendon-to-bone healing after anterior cruciate ligament (ACL) reconstruction. Methods. In vitro: the mobility of the rat bone mesenchymal stem cells (BMSCs) treated with SLPI was evaluated by scratch assay. Then the expression levels of osteogenic differentiation-related genes were analyzed by real-time quantitative PCR (qPCR) to determine the osteogenic effect of SLPI on BMSCs. In vivo: a rat model of ACL reconstruction was used to verify the effect of SLPI on tendon-to-bone healing. All the animals of the SLPI group and the negative control (NC) group were euthanized for histological evaluation, micro-CT scanning, and biomechanical testing. Results. SLPI improved the migration ability of BMSCs and upregulated the expression of genes related to osteogenic differentiation of BMSCs in vitro. In vivo, the SLPI group had higher histological scores at the tendon-bone interface by histological evaluation. Micro-CT showed more new bone formation and bone ingrowth around the grafted tendon in the SLPI group. Evaluation of the healing strength of the tendon-bone connection showed that the SLPI group had a higher maximum failure force and stiffness. Conclusion. SLPI can effectively promote early tendon-to-bone healing after ACL reconstruction via enhancing the migration and osteogenic differentiation of BMSCs. Cite this article: Bone Joint Res 2022;11(7):503–512

Objectives. Cortical and cancellous bone healing processes appear to be histologically different. They also respond differently to anti-inflammatory agents. We investigated whether the leucocyte composition on days 3 and 5 after cortical and cancellous injuries to bone was different, and compared changes over time using day 3 as the baseline. Methods. Ten-week-old male C56/Bl6J mice were randomized to either cancellous injury in the proximal tibia or cortical injury in the femoral diaphysis. Regenerating tissues were analyzed with flow cytometry at days 3 and 5, using panels with 15 antibodies for common macrophage and lymphocyte markers. The cellular response from day 3 to 5 was compared in order to identify differences in how cancellous and cortical bone healing develop. Results. Between day 3 and 5, the granulocytes increased in the cancellous model, whereas the lymphocytes (T cells, B cells, NK cells) and monocytes (CD11b+, F4/80+, CD206+, CD14+) increased in the cortical model. Conclusion. These results suggest an acute type of inflammation in cancellous bone healing, and a more chronic inflammation in cortical healing. This might explain, in part, why cancellous healing is faster and more resistant to anti-inflammatory drugs than are diaphyseal fractures. Cite this article: L. Tätting, O. Sandberg, M. Bernhardsson, J. Ernerudh, P. Aspenberg. Different composition of leucocytes in cortical and cancellous bone healing in a mouse model. Bone Joint Res 2018;7:620–628. DOI: 10.1302/2046-3758.712.BJR-2017-0366.R2

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

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

Aims. The purpose of this study was to validate our hypothesis that centrifugation may eliminate false-positive leucocyte esterase (LE) strip test results caused by autoimmune diseases in the diagnosis of knee infection. Methods. Between January 2016 and May 2019, 83 cases, including 33 cases of septic arthritis and 50 cases of aseptic arthritis, were enrolled in this study. To further validate our hypothesis, another 34 cases of inflammatory arthritis from the Department of Rheumatology of our institution were also included. After aspiration, one drop of synovial fluid was applied to LE strips before and after centrifugation. The results were recorded after approximately three minutes according to the different colour grades on the colour chart. The differences of LE results between each cohort were analyzed. Results. Before centrifugation, 46% (23/50) of the LE strip tests in the aseptic arthritis group were false-positives. Most of the false-positive results were due to inflammatory arthritis; after centrifugation, 78.3% (18/23) of the tests yielded negative results. Similar results were observed in cases from the Department of Rheumatology. The sensitivity of the centrifuged LE strip test was 0.818 (0.639 to 0.924), which is still an acceptable level compared with the uncentrifuged results, which yielded a sensitivity of 0.909 (0.745 to 0.976). However, the specificity was increased from 0.540 (0.395 to 0.679) to 0.900 (0.774 to 0.963) after centrifugation. Conclusion. Although inflammatory arthritis can yield a false-positive LE strip test result in the diagnosis of knee infection, centrifugation may eliminate these false-positive results. Cite this article: Bone Joint Res. 2020;9(5):236–241

Infection is a leading indication for revision arthroplasty. Established criteria used to diagnose prosthetic joint infection (PJI) include a range of laboratory tests. Leucocyte esterase (LE) is widely used on a colorimetric reagent strip for the diagnosis of urinary tract infections. This inexpensive test may be used for the diagnosis or exclusion of PJI. Aspirates from 30 total hip arthroplasties (THAs) and 79 knee arthroplasties (KA) were analysed for LE activity. Semi-quantitative reagent strip readings of 15, 70, 125 and 500 white blood cells (WBC) were validated against a manual synovial white cell count (WCC). A receiver operating characteristic (ROC) curve was constructed to determine the optimal cut-off point for the semi-quantitative results. Based on established criteria, six THAs and 15 KAs were classified as infected. The optimal cut-off point for the diagnosis of PJI was 97 WBC. The closest semi-quantitative reading for a positive result was 125 WBC, achieving a sensitivity of 81% and a specificity of 93%. The positive and negative predictive values of the LE test strip were 74% and 95% respectively. The LE reagent strip had a high specificity and negative predictive value. A negative result may exclude PJI and negate the need for further diagnostic tests. Cite this article: Bone Joint J 2015;97-B:1232–6

Aims

Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections.

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. 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. Methods. We investigated the effects of mCRP and the signalling pathways that are involved in cultured human primary annulus fibrosus (AF) cells and in the human nucleus pulposus (NP) immortalized cell line HNPSV-1. We determined messenger RNA (mRNA) and protein levels of relevant factors involved in inflammatory responses, by quantitative real-time polymerase chain reaction (RT-qPCR) and western blot. We also studied the presence of mCRP in human AF and NP tissues by immunohistochemistry. Results. We demonstrated that mCRP increases nitric oxide synthase 2 (NOS2), cyclooxygenase 2 (COX2), matrix metalloproteinase 13 (MMP13), vascular cell adhesion molecule 1 (VCAM1), interleukin (IL)-6, IL-8, and Lipocalin 2 (LCN2) expression in human AF and NP cells. We also showed that nuclear factor-κβ (NF-κβ), extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphoinositide 3-kinase (PI3K) are at play in the intracellular signalling of mCRP. Finally, we demonstrated the presence of mCRP in human AF and NP tissues. Conclusion. Our results indicate, for the first time, that mCRP can be localized in IVD tissues, where it triggers a proinflammatory and catabolic state in degenerative and healthy IVD cells, and that NF-κβ signalling may be implicated in the mediation of this mCRP-induced state. Cite this article: Bone Joint Res 2023;12(3):189–198

Aims. This study aimed, through bioinformatics analysis, to identify the potential diagnostic markers of osteoarthritis, and analyze the role of immune infiltration in synovial tissue. Methods. The gene expression profiles were downloaded from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by R software. Functional enrichment analyses were performed and protein-protein interaction networks (PPI) were constructed. Then the hub genes were screened. Biomarkers with high value for the diagnosis of early osteoarthritis (OA) were validated by GEO datasets. Finally, the CIBERSORT algorithm was used to evaluate the immune infiltration between early-stage OA and end-stage OA, and the correlation between the diagnostic marker and infiltrating immune cells was analyzed. Results. A total of 88 DEGs were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that DEGs were significantly enriched in leucocyte migration and interleukin (IL)-17 signalling pathways. Disease ontology (DO) indicated that DEGs were mostly enriched in rheumatoid arthritis. Six hub genes including FosB proto-oncogene, AP-1 transcription factor subunit (FOSB); C-X-C motif chemokine ligand 2 (CXCL2); CXCL8; IL-6; Jun proto-oncogene, AP-1 transcription factor subunit (JUN); and Activating transcription factor 3 (ATF3) were identified and verified by GEO datasets. ATF3 (area under the curve = 0.975) turned out to be a potential biomarker for the diagnosis of early OA. Several infiltrating immune cells varied significantly between early-stage OA and end-stage OA, such as resting NK cells (p = 0.016), resting dendritic cells (p = 0.043), and plasma cells (p = 0.043). Additionally, ATF3 was significantly correlated with resting NK cells (p = 0.034), resting dendritic cells (p = 0.026), and regulatory T cells (Tregs, p = 0.018). Conclusion. ATF3 may be a potential diagnostic marker for early diagnosis and treatment of OA, and immune cell infiltration provides new perspectives for understanding the mechanism during OA progression. Cite this article: Bone Joint Res 2022;11(9):679–689

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

Aims. The aims of this study were to increase the diagnostic accuracy of the analysis of synovial fluid in the differentiation of prosthetic joint infection (PJI) by the addition of inexpensive biomarkers such as the levels of C-reactive protein (CRP), adenosine deaminase (ADA), alpha-2-macrogloblulin (α2M) and procalcitonin. Patients and Methods. Between January 2013 and December 2015, synovial fluid and removed implants were requested from 143 revision total joint arthroplasties. A total of 55 patients met inclusion criteria of the receipt of sufficient synovial fluid, tissue samples and removed implants for analysis. The diagnosis of PJI followed the definition from a recent International Consensus Meeting to create two groups of patients; septic and aseptic. Using receiver operating characteristic curves we determined the cutoff values and diagnostic accuracy for each marker. Results. There were 23 PJIs and 32 patients with aseptic loosening. The levels of total leucocyte count, proportion of polymorphonuclear leucocytes (PMNs), CRP, ADA and α2M in the synovial fluid were all significantly higher in those with a PJI than in those with aseptic loosening. The levels of procalcitonin were comparable in the two groups. Cutoff values for the optimal performance in the diagnosis of infection were: total leucocyte count > 1463 cells/μL (sensitivity (Sens) 100%, specificity (Spec) 71.9%, positive predictive value (PPV) 71.9%, negative predictive value (NPV) 100%); proportion of PMNs > 81% (Sens 78.3%, Spec 75.0%, PPV 69.2%, NPV 82.8%); CRP > 6.7mg/L (Sens 78.3%, Spec 93.8%, PPV 90.0%, NPV 85.7%); ADA > 61U/L (Sens 78.3%, Spec 96.9%, PPV 94.7%, NPV 86.1%) and α2M > 958 mg/L (Sens 47.8%, Spec 96.9%, PPV 91.7%, NPV 72.1%). The addition of a raised level of CRP or ADA to the total leukocyte count increased the specificity: total leukocyte count > 1463 cells/μL and CRP > 6.7mg/L (Sens 78.3%, Spec 100%, PPV 100%, NPV 86.5%) or with ADA > 61U/L (Sens 78.3%, Spec 96.9%, PPV 94.7%, NPV 86.1%). . Conclusion. The total leucocyte count in the synovial fluid offers great negative predictive value in the diagnosis of PJI and the addition of more specific markers such as CRP and ADA improves the positive predictive value. Thus the addition of simple and inexpensive markers to the measurement of the leucocyte count in the synovial fluid may reduce the number of equivocal results which demand more expensive investigation. Cite this article: Bone Joint J 2017;99-B:351–7

As our understanding of hip function and disease improves, it is evident that the acetabular fossa has received little attention, despite it comprising over half of the acetabulum’s surface area and showing the first signs of degeneration. The fossa’s function is expected to be more than augmenting static stability with the ligamentum teres and being a templating landmark in arthroplasty. Indeed, the fossa, which is almost mature at 16 weeks of intrauterine development, plays a key role in hip development, enabling its nutrition through vascularization and synovial fluid, as well as the influx of chondrogenic stem/progenitor cells that build articular cartilage. The pulvinar, a fibrofatty tissue in the fossa, has the same developmental origin as the synovium and articular cartilage and is a biologically active area. Its unique anatomy allows for homogeneous distribution of the axial loads into the joint. It is composed of intra-articular adipose tissue (IAAT), which has adipocytes, fibroblasts, leucocytes, and abundant mast cells, which participate in the inflammatory cascade after an insult to the joint. Hence, the fossa and pulvinar should be considered in decision-making and surgical outcomes in hip preservation surgery, not only for their size, shape, and extent, but also for their biological capacity as a source of cytokines, immune cells, and chondrogenic stem cells. Cite this article: Bone Joint Res 2020;9(12):857–869

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. Compartment syndrome results from increased intra-compartmental pressure (ICP) causing local tissue ischaemia and cell death, but the systemic effects are not well described. We hypothesised that compartment syndrome would have a profound effect not only on the affected limb, but also on remote organs. Methods. Using a rat model of compartment syndrome, its systemic effects on the viability of hepatocytes and on inflammation and circulation were directly visualised using intravital video microscopy. Results. We found that hepatocellular injury was significantly higher in the compartment syndrome group (192 PI-labelled cells/10. -1 . mm. 3. , standard error of the mean (. sem. ) 51) compared with controls (30 PI-labelled cells/10. -1 . mm. 3. , . sem . 12, p < 0.01). The number of adherent venular white blood cells was significantly higher for the compartment syndrome group (5 leukocytes/30s/10 000 μm. 2. , . sem 1. ) than controls (0.2 leukocytes/30 s/10 000 μm. 2. , . sem . 0.2, p < 0.01). Volumetric blood flow was not significantly different between the two groups, although there was an increase in the heterogeneity of perfusion. Conclusions. Compartment syndrome can be accompanied by severe systemic inflammation and end organ damage. This study provides evidence of the relationship between compartment syndrome in a limb and systemic inflammation and dysfunction in a remote organ. Cite this article: Bone Joint J 2016; 98-B:1132–7

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. 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

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

Aims. To assess the diagnostic value of C-reactive protein (CRP), leucocyte count (LC), and erythrocyte sedimentation rate (ESR) in late fracture-related infection (FRI). Materials and Methods. PubMed, Embase, and Cochrane databases were searched focusing on the diagnostic value of CRP, LC, and ESR in late FRI. Sensitivity and specificity combinations were extracted for each marker. Average estimates were obtained using bivariate mixed effects models. Results. A total of 8284 articles were identified but only six were suitable for inclusion. Sensitivity of CRP ranged from 60.0% to 100.0% and specificity from 34.3% to 85.7% in all publications considered. Five articles were pooled for meta-analysis, showing a sensitivity and specificity of 77.0% and 67.9%, respectively. For LC, this was 22.9% to 72.6%, and 73.5% to 85.7%, respectively, in five articles. Four articles were pooled for meta-analysis, resulting in a 51.7% sensitivity and 67.1% specificity. For ESR, sensitivity and specificity ranged from 37.1% to 100.0% and 59.0% to 85.0%, respectively, in five articles. Three articles were pooled in meta-analysis, showing a 45.1% sensitivity and 79.3% specificity. Four articles analyzed the value of combined inflammatory markers, reporting an increased diagnostic accuracy. These results could not be pooled due to heterogeneity. Conclusion. The serum inflammatory markers CRP, LC, and ESR are insufficiently accurate to diagnose late FRI, but they may be used as a suggestive sign in its diagnosis