Aims. Options for the treatment of intra-articular ligament injuries are limited, and insufficient ligament reconstruction can cause painful joint instability, loss of function, and progressive development of degenerative arthritis. This study aimed to assess the capability of a biologically enhanced matrix material for ligament reconstruction to withstand tensile forces within the joint and enhance ligament regeneration needed to regain joint function. Materials and Methods. A total of 18 New Zealand rabbits underwent bilateral anterior cruciate ligament reconstruction by autograft, FiberTape, or FiberTape-augmented autograft. Primary outcomes were biomechanical assessment (n = 17), microCT (µCT) assessment (n = 12), histological evaluation (n = 12), and quantitative polymerase chain reaction (qPCR) analysis (n = 6). Results. At eight weeks, FiberTape alone or FiberTape-augmented autograft demonstrated increased biomechanical stability compared with autograft regarding ultimate load to failure (p = 0.035), elongation (p = 0.006), and energy absorption (p = 0.022). FiberTape-grafted samples also demonstrated increased bone mineral density in the bone tunnel (p = 0.039). Histological evaluation showed integration of all grafts in the bone tunnels by new bone formation, and limited signs of inflammation overall. A lack of prolonged inflammation in all samples was confirmed by quantification of inflammation biomarkers. However, no regeneration of ligament-like tissue was observed along the suture tape materials. Except for one autograft failure, no adverse events were detected. Conclusion. Our results indicate that FiberTape increases the biomechanical performance of intra-articular ligament reconstructions in a verified rabbit model at eight weeks. Within this period, FiberTape did not adversely affect bone tunnel healing or invoke a prolonged elevation in inflammation. Cite this article: Bone Joint J 2019;101-B:1238–1247

Aims. The optimum type of antibiotics and their administration route for treating Gram-negative (GN) periprosthetic joint infection (PJI) remain controversial. This study aimed to determine the GN bacterial species and antibacterial resistance rates related to clinical GN-PJI, and to determine the efficacy and safety of intra-articular (IA) antibiotic injection after one-stage revision in a GN pathogen-induced PJI rat model of total knee arthroplasty. Methods. A total of 36 consecutive PJI patients who had been infected with GN bacteria between February 2015 and December 2021 were retrospectively recruited in order to analyze the GN bacterial species involvement and antibacterial resistance rates. Antibiotic susceptibility assays of the GN bacterial species were performed to screen for the most sensitive antibiotic, which was then used to treat the most common GN pathogen-induced PJI rat model. The rats were randomized either to a PJI control group or to three meropenem groups (intraperitoneal (IP), IA, and IP + IA groups). After two weeks of treatment, infection control level, the side effects, and the volume of antibiotic use were evaluated. Results. Escherichia coli was the most common pathogen in GN-PJI, and meropenem was the most sensitive antibiotic. Serum inflammatory markers, weightbearing activity, and Rissing score were significantly improved by meropenem, especially in the IA and IP + IA groups ( p < 0.05). Meropenem in the IA group eradicated E. coli from soft-tissue, bone, and prosthetic surfaces, with the same effect as in the IP + IA group. Radiological results revealed that IA and IP + IA meropenem were effective at relieving bone damage. Haematoxylin and eosin staining also showed that IA and IP + IA meropenem improved synovial inflammation and bone destruction. No pathological changes in the main organs or abnormal serum markers were observed in any of the meropenem-treated rats. The IA group required the lowest amount of meropenem, followed by the IP and IP + IA groups. Conclusion. IA-only meropenem with a two-week treatment course was effective and safe for PJI control following one-stage revision in a rat model, with less meropenem use. Cite this article: Bone Joint Res 2024;13(10):546–558

Aims. Intravenous dexamethasone has been shown to reduce immediate postoperative pain after total hip arthroplasty (THA), though the effects are short-lived. We aimed to assess whether two equivalent perioperative split doses were more effective than a single preoperative dose. Methods. A total of 165 patients were randomly assigned into three groups: two perioperative saline injections (Group A, placebo), a single preoperative dose of 20 mg dexamethasone and a postoperative saline injection (Group B), and two perioperative doses of 10 mg dexamethasone (Group C). Patients, surgeons, and staff collecting outcome data were blinded to allocation. The primary outcome was postoperative pain level reported on a ten-point Numerical Rating Scale (NRS) at rest and during activity. The use of analgesic and antiemetic rescue, incidence of postoperative nausea and vomiting (PONV), CRP and interleukin-6 (IL-6) levels, range of motion (ROM), length of stay (LOS), patient satisfaction, and the incidence of surgical site infection (SSI) and gastrointestinal bleeding (GIB) in the three months postoperatively, were also compared. Results. The pain scores at rest were significantly lower in Groups B and C than in Group A on postoperative days 1 and 2. The dynamic pain scores and CRP and IL-6 levels were significantly lower for Groups B and C compared to Group A on postoperative days 1, 2, and 3. Patients in Groups B and C had a lower incidence of PONV, reduced use of analgesic and antiemetic rescue, improved ROM, shorter LOS, and reported higher satisfaction than in Group A. Patients in Group C had significantly lower dynamic pain scores and IL-6 and CRP levels on postoperative days 2 and 3, and higher ROM and satisfaction on postoperative day 3 than in Group B. No SSI or GIB occurred in any group. Conclusion. Perioperative dexamethasone provides short-term advantages in reducing pain, PONV, and inflammation, and increasing range of motion in the early postoperative period after THA. A split-dose regimen was superior to a single high dose in reducing pain and inflammation, and increasing ROM, with better patient satisfaction. Level of evidence: I. Cite this article: Bone Joint J 2020;102-B(11):1497–1504

Objectives. Healing in cancellous metaphyseal bone might be different from midshaft fracture healing due to different access to mesenchymal stem cells, and because metaphyseal bone often heals without a cartilaginous phase. Inflammation plays an important role in the healing of a shaft fracture, but if metaphyseal injury is different, it is important to clarify if the role of inflammation is also different. The biology of fracture healing is also influenced by the degree of mechanical stability. It is unclear if inflammation interacts with stability-related factors. Methods. We investigated the role of inflammation in three different models: a metaphyseal screw pull-out, a shaft fracture with unstable nailing (IM-nail) and a stable external fixation (ExFix) model. For each, half of the animals received dexamethasone to reduce inflammation, and half received control injections. Mechanical and morphometric evaluation was used. Results. As expected, dexamethasone had a strong inhibitory effect on the healing of unstable, but also stable, shaft fractures. In contrast, dexamethasone tended to increase the mechanical strength of metaphyseal bone regenerated under stable conditions. Conclusions. It seems that dexamethasone has different effects on metaphyseal and diaphyseal bone healing. This could be explained by the different role of inflammation at different sites of injury. Cite this article: Bone Joint Res 2015;4:170–175

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. Methods. The OA model was established by anterior cruciate ligament transection with medial meniscectomy in Wistar rats. The poly (ADP-ribose) polymerase 1 (PARP-1) shRNA (short hairpin (sh)-PARP-1) and negative control shRNA (sh-NC) were delivered using a lentiviral vector and were intra-articularly injected into rats after surgery. The weight-bearing distribution of the hind limbs and the knee joint width were measured every two weeks. The expression levels of PARP-1, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) in cartilage were determined using real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. The serum concentrations of inflammatory cytokines were detected using enzyme-linked immunosorbent assay (ELISA). Results. PARP-1 expression level significantly increased in the cartilage of the established OA rat model. sh-PARP-1 treatment suppressed PARP-1 levels, decreased the Δ Force (the difference between the weight on ipsilateral limb and contralateral limb) and the knee joint width, inhibited cartilage matrix catabolic enzymes, and ameliorated OA cartilage degradation and attenuated inflammatory response. Conclusion. PARP-1 inhibition attenuates OA cartilage inflammatory response in the OA rat model. Cite this article: Bone Joint Res 2021;10(7):401–410

Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetrical and chronic polyarthritis. Fibroblast-like synoviocytes are mainly involved in joint inflammation and cartilage and bone destruction by inflammatory cytokines and matrix-degrading enzymes in RA. Approaches that induce various cellular growth alterations of synoviocytes are considered as potential strategies for treating RA. However, since synoviocytes play a critical role in RA, the mechanism and hyperplastic modulation of synoviocytes and their motility need to be addressed. In this review, we focus on the alteration of synoviocyte signalling and cell fate provided by signalling proteins, various antioxidant molecules, enzymes, compounds, clinical candidates, to understand the pathology of the synoviocytes, and finally to achieve developed therapeutic strategies of RA. Cite this article: Bone Joint Res 2021;10(4):285–297

Aims. The aim of this study was to examine whether tourniquet use can improve perioperative blood loss, early function recovery, and pain after primary total knee arthroplasty (TKA) in the setting of multiple-dose intravenous tranexamic acid. Methods. This was a prospective, randomized clinical trial including 180 patients undergoing TKA with multiple doses of intravenous tranexamic acid. One group was treated with a tourniquet during the entire procedure, the second group received a tourniquet during cementing, and the third group did not receive a tourniquet. All patients received the same protocol of intravenous tranexamic acid (20 mg/kg) before skin incision, and three and six hours later (10 mg/kg). The primary outcome measure was perioperative blood loss. Secondary outcome measures were creatine kinase (CK), CRP, interleukin-6 (IL-6), visual analogue scale (VAS) pain score, limb swelling ratio, quadriceps strength, straight leg raising, range of motion (ROM), American Knee Society Score (KSS), and adverse events. Results. The mean total blood loss was lowest in the no-tourniquet group at 867.32 ml (SD 201.11), increased in the limited-tourniquet group at 1024.35 ml (SD 176.35), and was highest in the tourniquet group at 1,213.00 ml (SD 211.48). The hidden blood loss was lowest in the no-tourniquet group (both p < 0.001). There was less mean intraoperative blood loss in the tourniquet group (77.48 ml (SD 24.82)) than in the limited-tourniquet group (137.04 ml (SD 26.96)) and the no-tourniquet group (212.99 ml (SD 56.35); both p < 0.001). Patients in the tourniquet group showed significantly higher levels of muscle damage and inflammation biomarkers such as CK, CRP, and IL-6 than the other two groups (p < 0.05). Outcomes for VAS pain scores, limb swelling ratio, quadriceps strength, straight leg raising, ROM, and KSS were significantly better in the no-tourniquet group at three weeks postoperatively (p < 0.05), but there were no significant differences at three months. No significant differences were observed among the three groups with respect to transfusion rate, thrombotic events, or the length of hospital stay. Conclusion. Patients who underwent TKA with multiple doses of intravenous tranexamic acid but without a tourniquet presented lower total blood loss and hidden blood loss, and they showed less postoperative inflammation reaction, less muscle damage, lower VAS pain score, and better early knee function. Our results argue for not using a tourniquet during TKA. Cite this article: Bone Joint Res 2020;9(6):322–332

Aims. The prevalence of osteoarthritis (OA) associated with instability of the shoulder ranges between 4% and 60%. Articular cartilage is, however, routinely assessed in these patients using radiographs or scans (2D or 3D), with little opportunity to record early signs of cartilage damage. The aim of this study was to assess the prevalence and localization of chondral lesions and synovial damage in patients undergoing arthroscopic surgery for instablility of the shoulder, in order to classify them and to identify risk factors for the development of glenohumeral OA. Methods. A total of 140 shoulders in 140 patients with a mean age of 28.5 years (15 to 55), who underwent arthroscopic treatment for recurrent glenohumeral instability, were included. The prevalence and distribution of chondral lesions and synovial damage were analyzed and graded into stages according to the division of the humeral head and glenoid into quadrants. The following factors that might affect the prevalence and severity of chondral damage were recorded: sex, dominance, age, age at the time of the first dislocation, number of dislocations, time between the first dislocation and surgery, preoperative sporting activity, Beighton score, type of instability, and joint laxity. Results. A total of 133 patients (95%) had synovial or chondral lesions. At the time of surgery, shoulders were graded as having mild, moderate, and severe OA in 55 (39.2%), 72 (51.4%), and six (4.2%) patients, respectively. A Hill-Sachs lesion and fibrillation affecting the anteroinferior glenoid cartilage were the most common findings. There was a significant positive correlation between the the severity of the development of glenohumeral OA and the patient’s age, their age at the time of the first dislocation, and the number of dislocations (p = 0.004, p = 0.011, and p = 0.031, respectively). Conclusion. Synovial inflammation and chondral damage associated with instability of the shoulder are more prevalent than previously reported. The classification using quadrants gives surgeons more information about the chondral damage, and could explain the pattern of development of glenohumeral OA after stabilization of the shoulder. As the number of dislocations showed a positive correlation with the development of OA, this might be an argument for early stabilization. Cite this article: Bone Joint J 2024;106-B(10):1125–1132

Objectives. The long head of the biceps (LHB) is often resected in shoulder surgery and could therefore serve as a cell source for tissue engineering approaches in the shoulder. However, whether it represents a suitable cell source for regenerative approaches, both in the inflamed and non-inflamed states, remains unclear. In the present study, inflamed and native human LHBs were comparatively characterized for features of regeneration. Methods. In total, 22 resected LHB tendons were classified into inflamed samples (n = 11) and non-inflamed samples (n = 11). Proliferation potential and specific marker gene expression of primary LHB-derived cell cultures were analyzed. Multipotentiality, including osteogenic, adipogenic, chondrogenic, and tenogenic differentiation potential of both groups were compared under respective lineage-specific culture conditions. Results. Inflammation does not seem to affect the proliferation rate of the isolated tendon-derived stem cells (TDSCs) and the tenogenic marker gene expression. Cells from both groups showed an equivalent osteogenic, adipogenic, chondrogenic and tenogenic differentiation potential in histology and real-time polymerase chain reaction (RT-PCR) analysis. Conclusion. These results suggest that the LHB tendon might be a suitable cell source for regenerative approaches, both in inflamed and non-inflamed states. The LHB with and without tendinitis has been characterized as a novel source of TDSCs, which might facilitate treatment of degeneration and induction of regeneration in shoulder surgery. Cite this article: J. Schmalzl, P. Plumhoff, F. Gilbert, F. Gohlke, C. Konrads, U. Brunner, F. Jakob, R. Ebert, A. F. Steinert. Tendon-derived stem cells from the long head of the biceps tendon: Inflammation does not affect the regenerative potential. Bone Joint Res 2019;8:414–424. DOI: 10.1302/2046-3758.89.BJR-2018-0214.R2

Aims. Interleukin (IL)-1β is one of the major pathogenic regulators during the pathological development of intervertebral disc degeneration (IDD). However, effective treatment options for IDD are limited. Suramin is used to treat African sleeping sickness. This study aimed to investigate the pharmacological effects of suramin on mitigating IDD and to characterize the underlying mechanism. Methods. Porcine nucleus pulposus (NP) cells were treated with vehicle, 10 ng/ml IL-1β, 10 μM suramin, or 10 μM suramin plus IL-1β. The expression levels of catabolic and anabolic proteins, proinflammatory cytokines, mitogen-activated protein kinase (MAPK), and nuclear factor (NF)-κB-related signalling molecules were assessed by Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), and immunofluorescence analysis. Flow cytometry was applied to detect apoptotic cells. The ex vivo effects of suramin were examined using IDD organ culture and differentiation was analyzed by Safranin O-Fast green and Alcian blue staining. Results. Suramin inhibited IL-1β-induced apoptosis, downregulated matrix metalloproteinase (MMP)-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, and ADAMTS-5, and upregulated collagen 2A (Col2a1) and aggrecan in IL-1β-treated NP cells. IL-1β-induced inflammation, assessed by IL-1β, IL-8, and tumour necrosis factor α (TNF-α) upregulation, was alleviated by suramin treatment. Suramin suppressed IL-1β-mediated proteoglycan depletion and the induction of MMP-3, ADAMTS-4, and pro-inflammatory gene expression in ex vivo experiments. Conclusion. Suramin administration represents a novel and effectively therapeutic approach, which could potentially alleviate IDD by reducing extracellular matrix (ECM) deposition and inhibiting apoptosis and inflammatory responses in the NP cells. Cite this article: Bone Joint Res 2021;10(8):498–513

Aims. The purpose of this study was to examine the efficacy and safety of carbazochrome sodium sulfonate (CSS) combined with tranexamic acid (TXA) on blood loss and inflammatory responses after primary total hip arthroplasty (THA), and to investigate the influence of different administration methods of CSS on perioperative blood loss during THA. Methods. This study is a randomized controlled trial involving 200 patients undergoing primary unilateral THA. A total of 200 patients treated with intravenous TXA were randomly assigned to group A (combined intravenous and topical CSS), group B (topical CSS), group C (intravenous CSS), or group D (placebo). Results. Mean total blood loss (TBL) in groups A (605.0 ml (SD 235.9)), B (790.9 ml (SD 280.7)), and C (844.8 ml (SD 248.1)) were lower than in group D (1,064.9 ml (SD 318.3), p < 0.001). We also found that compared with group D, biomarker level of inflammation, transfusion rate, pain score, and hip range of motion at discharge in groups A, B, and C were significantly improved. There were no differences among the four groups in terms of intraoperative blood loss (IBL), intramuscular venous thrombosis (IMVT), and length of hospital stay (LOS). Conclusion. The combined application of CSS and TXA is more effective than TXA alone in reducing perioperative blood loss and transfusion rates, inflammatory response, and postoperative hip pain, results in better early hip flexion following THA, and did not increase the associated venous thromboembolism (VTE) events. Intravenous combined with topical injection of CSS was superior to intravenous or topical injection of CSS alone in reducing perioperative blood loss. Cite this article: Bone Joint Res 2021;10(6):354–362

Osteoarthritis (OA), one of the most common motor system disorders, is a degenerative disease involving progressive joint destruction caused by a variety of factors. At present, OA has become the fourth most common cause of disability in the world. However, the pathogenesis of OA is complex and has not yet been clarified. Long non-coding RNA (lncRNA) refers to a group of RNAs more than 200 nucleotides in length with limited protein-coding potential, which have a wide range of biological functions including regulating transcriptional patterns and protein activity, as well as binding to form endogenous small interference RNAs (siRNAs) and natural microRNA (miRNA) molecular sponges. In recent years, a large number of lncRNAs have been found to be differentially expressed in a variety of pathological processes of OA, including extracellular matrix (ECM) degradation, synovial inflammation, chondrocyte apoptosis, and angiogenesis. Obviously, lncRNAs play important roles in regulating gene expression, maintaining the phenotype of cartilage and synovial cells, and the stability of the intra-articular environment. This article reviews the results of the latest research into the role of lncRNAs in a variety of pathological processes of OA, in order to provide a new direction for the study of OA pathogenesis and a new target for prevention and treatment. Cite this article: Bone Joint Res 2021;10(2):122–133

Aims. Rheumatoid arthritis (RA), which mainly results from fibroblast-like synoviocyte (FLS) dysfunction, is related to oxidative stress. Advanced oxidation protein products (AOPPs), which are proinflammatory mediators and a novel biomarker of oxidative stress, have been observed to accumulate significantly in the serum of RA patients. Here, we present the first investigation of the effects of AOPPs on RA-FLSs and the signalling pathway involved in AOPP-induced inflammatory responses and invasive behaviour. Methods. We used different concentrations of AOPPs (50 to 200 µg/ml) to treat RA-FLSs. Cell migration and invasion and the expression levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), matrix metalloproteinase-3 (MMP-3), and MMP-13 were investigated. Western blot and immunofluorescence were used to analyze nuclear factor-κB (NF-κB) activation. Results. AOPPs promoted RA-FLS migration and invasion in vitro and significantly induced the messenger RNA (mRNA) and protein expression of TNF-α, IL-6, MMP-3, and MMP-13 in dose- and time-dependent manners. Moreover, AOPPs markedly activated the phosphorylation of nuclear factor-κB (NF-κB) p65 protein, which triggered inhibitory kappa B-alpha (IκBα) degradation, NF-κB p65 protein phosphorylation, and NF-κB p65 translocation into the nucleus. Furthermore, treatment with a neutralizing antibody specific to receptor for advanced glycation end products (RAGE) significantly suppressed aggressive behaviour and inflammation, decreased TNF-α, IL-6, MMP-3, and MMP-13 expression, and blocked AOPP-induced NF-κB pathway activation. Conclusion. The results indicate that AOPPs can enhance aggressive behaviour and the inflammatory response in RA-FLSs via the RAGE–NF-κB pathway. These results present AOPPs as a new class of potentially important mediators of progressive disease in RA patients. Cite this article: Bone Joint Res 2021;10(4):259–268

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 diagnosis of joint infections is an inexact science using combinations of blood inflammatory markers and microscopy, culture, and sensitivity of synovial fluid (SF). There is potential for small molecule metabolites in infected SF to act as infection markers that could improve accuracy and speed of detection. The objective of this study was to use nuclear magnetic resonance (NMR) spectroscopy to identify small molecule differences between infected and noninfected human SF. Methods. In all, 16 SF samples (eight infected native and prosthetic joints plus eight noninfected joints requiring arthroplasty for end-stage osteoarthritis) were collected from patients. NMR spectroscopy was used to analyze the metabolites present in each sample. Principal component analysis and univariate statistical analysis were undertaken to investigate metabolic differences between the two groups. Results. A total of 16 metabolites were found in significantly different concentrations between the groups. Three were in higher relative concentrations (lipids, cholesterol, and N-acetylated molecules) and 13 in lower relative concentrations in the infected group (citrate, glycine, glycosaminoglycans, creatinine, histidine, lysine, formate, glucose, proline, valine, dimethylsulfone, mannose, and glutamine). Conclusion. Metabolites found in significantly greater concentrations in the infected cohort are markers of inflammation and infection. They play a role in lipid metabolism and the inflammatory response. Those found in significantly reduced concentrations were involved in carbohydrate metabolism, nucleoside metabolism, the glutamate metabolic pathway, increased oxidative stress in the diseased state, and reduced articular cartilage breakdown. This is the first study to demonstrate differences in the metabolic profile of infected and noninfected human SF, using a noninfected matched cohort, and may represent putative biomarkers that form the basis of new diagnostic tests for infected SF. Cite this article: Bone Joint Res 2021;10(1):85–95

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. Methods. This prospective randomized controlled trial included 30 patients with osteoarthritis of the knee undergoing conventional TKA versus robotic TKA. Predefined serum markers of inflammation and localized knee temperature were collected preoperatively and postoperatively at six hours, day 1, day 2, day 7, and day 28 following TKA. Blinded observers used the Macroscopic Soft Tissue Injury (MASTI) classification system to grade intraoperative periarticular soft tissue injury and bone trauma. Plain radiographs were used to assess the accuracy of achieving the planned postioning of the components in both groups. Results. Patients undergoing conventional TKA and robotic TKA had comparable changes in the postoperative systemic inflammatory and localized thermal response at six hours, day 1, day 2, and day 28 after surgery. Robotic TKA had significantly reduced levels of interleukin-6 (p < 0.001), tumour necrosis factor-α (p = 0.021), ESR (p = 0.001), CRP (p = 0.004), lactate dehydrogenase (p = 0.007), and creatine kinase (p = 0.004) at day 7 after surgery compared with conventional TKA. Robotic TKA was associated with significantly improved preservation of the periarticular soft tissue envelope (p < 0.001), and reduced femoral (p = 0.012) and tibial (p = 0.023) bone trauma compared with conventional TKA. Robotic TKA significantly improved the accuracy of achieving the planned limb alignment (p < 0.001), femoral component positioning (p < 0.001), and tibial component positioning (p < 0.001) compared with conventional TKA. Conclusion. Robotic TKA was associated with a transient reduction in the early (day 7) postoperative inflammatory response but there was no difference in the immediate (< 48 hours) or late (day 28) postoperative systemic inflammatory response compared with conventional TKA. Robotic TKA was associated with decreased iatrogenic periarticular soft tissue injury, reduced femoral and tibial bone trauma, and improved accuracy of component positioning compared with conventional TKA. Cite this article: Bone Joint J 2021;103-B(1):113–122

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. Synovial fluid white blood cell (WBC) count and percentage of polymorphonuclear cells (%PMN) are elevated at periprosthetic joint infection (PJI). Leucocytes produce different interleukins (IL), including IL-6, so we hypothesized that synovial fluid IL-6 could be a more accurate predictor of PJI than synovial fluid WBC count and %PMN. The main aim of our study was to compare the predictive performance of all three diagnostic tests in the detection of PJI. Methods. Patients undergoing total hip or knee revision surgery were included. In the perioperative assessment phase, synovial fluid WBC count, %PMN, and IL-6 concentration were measured. Patients were labeled as positive or negative according to the predefined cut-off values for IL-6 and WBC count with %PMN. Intraoperative samples for microbiological and histopathological analysis were obtained. PJI was defined as the presence of sinus tract, inflammation in histopathological samples, and growth of the same microorganism in a minimum of two or more samples out of at least four taken. Results. In total, 49 joints in 48 patients (mean age 68 years (SD 10; 26 females (54%), 25 knees (51%)) were included. Of these 11 joints (22%) were infected. The synovial fluid WBC count and %PMN predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 82%, 97%, 94%, 90%, and 95%, respectively. Synovial fluid IL-6 predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 73%, 95%, 90%, 80%, and 92%, respectively. A comparison of predictive performance indicated a strong agreement between tests. Conclusions. Synovial fluid IL-6 is not superior to synovial fluid WBC count and %PMN in detecting PJI. Level of Evidence: Therapeutic Level II. Cite this article: Bone Jt Open 2020;1-12:737–742

Aims. Rheumatoid arthritis (RA) is a systematic autoimmune disorder, characterized by synovial inflammation, bone and cartilage destruction, and disease involvement in multiple organs. Although numerous drugs are employed in RA treatment, some respond little and suffer from severe side effects. This study aimed to screen the candidate therapeutic targets and promising drugs in a novel method. Methods. We developed a module-based and cumulatively scoring approach that is a deeper-layer application of weighted gene co-expression network (WGCNA) and connectivity map (CMap) based on the high-throughput datasets. Results. Four noteworthy RA-related modules were identified, revealing the immune- and infection-related biological processes and pathways involved in RA. HLA-DMA, HLA-DMB, HLA-DPA1, HLA-DPB1, HLA-DQB1, HLA-DRA, HLA-DRB1, BLNK, BTK, CD3D, CD4, IL2RG, INPP5D, LCK, PTPRC, RAC2, SYK, and VAV1 were recognized as the key hub genes with high connectivity in gene regulation networks and gene pathway networks. Moreover, the long noncoding RNAs (lncRNAs) in the RA-related modules, such as FAM30A and NEAT1, were identified as the indispensable interactors with the hub genes. Finally, candidate drugs were screened by developing a cumulatively scoring approach based on the selected modules. Niclosamide and the other compounds of T-type calcium channel blocker, IKK inhibitor, and PKC activator, HIF activator, and proteasome inhibitor, which harbour the similar gene signature with niclosamide, were promising drugs with high specificity and broad coverage for the RA-related modules. Conclusion. This study provides not only the promising targets and drugs for RA but also a novel methodological insight into the target and drug screening. Cite this article: Bone Joint Res 2020;9(8):501–514