Aims. Revision rates for ankle arthroplasties are higher than hip or knee arthroplasties. When a total ankle arthroplasty (TAA) fails, it can either undergo revision to another ankle replacement, revision of the TAA to ankle arthrodesis (fusion), or amputation. Currently there is a paucity of literature on the outcomes of these revisions. The aim of this meta-analysis is to assess the outcomes of revision TAA with respect to surgery type, functional outcomes, and reoperations. Methods. A systematic review was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Medline, Embase, Cinahl, and Cochrane reviews were searched for relevant papers. Papers analyzing surgical treatment for failed ankle arthroplasties were included. All papers were reviewed by two authors. Overall, 34 papers met the inclusion criteria. A meta-analysis of proportions was performed. Results. Six papers analyzed all-cause reoperations of revision ankle arthroplasties, and 14 papers analyzed failures of conversion of a TAA to fusion. It was found that 26.9% (95% confidence interval (CI) 15.4% to 40.1%) of revision ankle arthroplasties required further surgical intervention and 13.0% (95% CI 4.9% to 23.4%) of conversion to fusions; 14.4% (95% CI 8.4% to 21.4%) of revision ankle arthroplasties failed and 8% (95% CI 4% to 13%) of conversion to fusions failed. Conclusion. Revision of primary TAA can be an effective procedure with improved functional outcomes, but has considerable risks of failure and reoperation, especially in those with periprosthetic joint infection. In those who undergo conversion of TAA to fusion, there are high rates of nonunion. Further comparative studies are required to compare both operative techniques. Cite this article: Bone Jt Open 2022;3(7):596–606

Aims. To determine the likelihood of achieving a successful closed reduction (CR) of a dislocated hip in developmental dysplasia of the hip (DDH) after failed Pavlik harness treatment We report the rate of avascular necrosis (AVN) and the need for further surgical procedures. Methods. Data was obtained from the Northern Ireland DDH database. All children who underwent an attempted closed reduction between 2011 and 2016 were identified. Children with a dislocated hip that failed Pavlik harness treatment were included in the study. Successful closed reduction was defined as a hip that reduced in theatre and remained reduced. Most recent imaging was assessed for the presence of AVN using the Kalamchi and MacEwen classification. Results. There were 644 dislocated hips in 543 patients initially treated in Pavlik harness. In all, 67 hips failed Pavlik harness treatment and proceeded to arthrogram (CR) under general anaesthetic at an average age of 180 days. The number of hips that were deemed reduced in theatre was 46 of the 67 (69%). A total of 11 hips re-dislocated and underwent open reduction, giving a true successful CR rate of 52%. For the total cohort of 67 hips that went to theatre for arthrogram and attempted CR, five (7%) developed clinically significant AVN at an average follow-up of four years and one month, while none of the 35 hips whose reduction was truly successful developed clinically significant AVN. Conclusion. The likelihood of a successful closed reduction of a dislocated hip in the Northern Ireland population, which has failed Pavlik harness treatment, is 52% with a clinically significant AVN rate of 7%. As such, we continue to advocate closed reduction under general anaesthetic for the hip that has failed Pavlik harness. Cite this article: Bone Jt Open 2021;2(8):594–598

Aims

Metal particles detached from metal-on-metal hip prostheses (MoM-THA) have been shown to cause inflammation and destruction of tissues. To further explore this, we investigated the histopathology (aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL) score) and metal concentrations of the periprosthetic tissues obtained from patients who underwent revision knee arthroplasty. We also aimed to investigate whether accumulated metal debris was associated with ALVAL-type reactions in the synovium.

Objectives. T-cells are considered to play an important role in the inflammatory response causing arthroplasty failure. The study objectives were to investigate the composition and distribution of CD4+ T-cell phenotypes in the peripheral blood (PB) and synovial fluid (SF) of patients undergoing revision surgery for failed metal-on-metal (MoM) and metal-on-polyethylene (MoP) hip arthroplasties, and in patients awaiting total hip arthroplasty. Methods. In this prospective case-control study, PB and SF were obtained from 22 patients (23 hips) undergoing revision of MoM (n = 14) and MoP (n = 9) hip arthroplasties, with eight controls provided from primary hip osteoarthritis cases awaiting arthroplasty. Lymphocyte subtypes in samples were analysed using flow cytometry. Results. The percentages of CD4+ T-cell subtypes in PB were not different between groups. The CD4+ T-cells in the SF of MoM hips showed a completely different distribution of phenotypes compared with that found in the PB in the same patients, including significantly decreased CD4+ T-central memory cells (p < 0.05) and increased T-effector memory cells (p < 0.0001) in the SF. Inducible co-stimulator (ICOS) was the only co-stimulatory molecule with different expression on CD4+ CD28+ cells between groups. In PB, ICOS expression was increased in MoM (p < 0.001) and MoP (p < 0.05) cases compared with the controls. In SF, ICOS expression was increased in MoM hips compared with MoP hips (p < 0.05). Conclusions. Increased expression of ICOS on CD4+ T-cells in PB and SF of patients with failed arthroplasties suggests that these cells are activated and involved in generating immune responses. Variations in ICOS expression between MoM and MoP hips may indicate different modes of arthroplasty failure. Cite this article: Professor P. A. Revell. Increased expression of inducible co-stimulator on CD4+ T-cells in the peripheral blood and synovial fluid of patients with failed hip arthroplasties. Bone Joint Res 2016;5:52–60. doi: 10.1302/2046-3758.52.2000574

Aims. The volume of ambulatory total hip arthroplasty (THA) procedures is increasing due to the emphasis on value-based care. The purpose of the study is to identify the causes for failed same-day discharge (SDD) and perioperative factors leading to failed SDD. Methods. This retrospective cohort study followed pre-selected patients for SDD THA from 1 August 2018 to 31 December 2020. Inclusion criteria were patients undergoing unilateral THA with appropriate social support, age 18 to 75 years, and BMI < 37 kg/m. 2. Patients with opioid dependence, coronary artery disease, and valvular heart disease were excluded. Demographics, comorbidities, and perioperative data were collected from the electronic medical records. Possible risk factors for failed SDD were identified using multivariate logistic regression. Results. In all, 278 patients were identified with a mean age of 57.1 years (SD 8.1) and a mean BMI of 27.3 kg/m. 2. (SD 4.5). A total of 96 patients failed SDD, with the most common reasons being failure to clear physical therapy (26%), dizziness (22%), and postoperative nausea and vomiting (11%). Risk factors associated with failed SDD included smokers (odds ratio (OR) 6.24; p = 0.009), a maximum postoperative pain score > 8 (OR 4.76; p = 0.004), and procedures starting after 11 am (OR 2.28; p = 0.015). A higher postoperative tolerable pain goal (numerical rating scale 4 to 10) was found to be associated with successful SDD (OR 2.7; p = 0.001). Age, BMI, surgical approach, American Society of Anesthesiologists grade, and anaesthesia type were not associated with failed SDD. Conclusion. SDD is a safe and viable option for pre-selected patients interested in rapid recovery THA. The most common causes for failure to launch were failing to clear physical thereapy and patient symptomatology. Risk factors associated with failed SSD highlight the importance of preoperative counselling regarding smoking cessation and postoperative pain to set reasonable expectations. Future interventions should aim to improve patient postoperative mobilization, pain control, and decrease symptomatology. Cite this article: Bone Jt Open 2022;3(9):684–691

Aims. When performing revision total hip arthroplasty using diaphyseal-engaging titanium tapered stems (TTS), the recommended 3 to 4 cm of stem-cortical diaphyseal contact may not be available. In challenging cases such as these with only 2 cm of contact, can sufficient axial stability be achieved and what is the benefit of a prophylactic cable? This study sought to determine, first, whether a prophylactic cable allows for sufficient axial stability when the contact length is 2 cm, and second, if differing TTS taper angles (2° vs 3.5°) impact these results. Methods. A biomechanical matched-pair cadaveric study was designed using six matched pairs of human fresh cadaveric femora prepared so that 2 cm of diaphyseal bone engaged with 2° (right femora) or 3.5° (left femora) TTS. Before impaction, three matched pairs received a single 100 lb-tensioned prophylactic beaded cable; the remaining three matched pairs received no cable adjuncts. Specimens underwent stepwise axial loading to 2600 N or until failure, defined as stem subsidence > 5 mm. Results. All specimens without cable adjuncts (6/6 femora) failed during axial testing, while all specimens with a prophylactic cable (6/6) successfully resisted axial load, regardless of taper angle. In total, four of the failed specimens experienced proximal longitudinal fractures, three of which occurred with the higher 3.5° TTS. One fracture occurred in a 3.5° TTS with a prophylactic cable yet passed axial testing, subsiding < 5 mm. Among specimens with a prophylactic cable, the 3.5° TTS resulted in lower mean subsidence (0.5 mm (SD 0.8)) compared with the 2° TTS (2.4 mm (SD 1.8)). Conclusion. A single prophylactic beaded cable dramatically improved initial axial stability when stem-cortex contact length was 2 cm. All implants failed secondary to fracture or subsidence > 5 mm when a prophylactic cable was not used. A higher taper angle appears to decrease the magnitude of subsidence but increased the fracture risk. The fracture risk was mitigated by the use of a prophylactic cable. Cite this article: Bone Jt Open 2023;4(7):472–477

Tennis elbow (lateral epicondylitis or lateral elbow tendinopathy) is a self-limiting condition in most patients. Surgery is often offered to patients who fail to improve with conservative treatment. However, there is no evidence to support the superiority of surgery over continued nonoperative care or no treatment. New evidence also suggests that the prognosis of tennis elbow is not influenced by the duration of symptoms, and that there is a 50% probability of recovery every three to four months. This finding challenges the belief that failed nonoperative care is an indication for surgery. In this annotation, we discuss the clinical and research implications of the benign clinical course of tennis elbow. Cite this article: Bone Joint J 2023;105-B(2):109–111

Aims. After failed acetabular fractures, total hip arthroplasty (THA) is a challenging procedure and considered the gold standard treatment. The complexity of the procedure depends on the fracture pattern and the initial fracture management. This study’s primary aim was to evaluate patient-reported outcome measures (PROMs) for patients who underwent delayed uncemented acetabular THA after acetabular fractures. The secondary aims were to assess the radiological outcome and the incidence of the associated complications in those patients. Methods. A total of 40 patients underwent cementless acetabular THA following failed treatment of acetabular fractures. The postoperative clinical and radiological outcomes were evaluated for all the cohort. Results. The median (interquartile range (IQR)) Oxford Hip Score (OHS) improved significantly from 9.5 (7 to 11.5), (95% confidence interval (CI) (8 to 10.6)) to 40 (39 to 44), (95% CI (40 to 43)) postoperatively at the latest follow-up (p < 0.001). It was worth noting that the initial acetabular fracture type (simple vs complex), previous acetabular treatment (ORIF vs conservative), fracture union, and restoration of anatomical centre of rotation (COR) did not affect the final OHS. The reconstructed centre of rotation (COR) was restored in 29 (72.5%) patients. The mean abduction angle in whom acetabular fractures were managed conservatively was statistically significantly higher than the surgically treated patients 42.6° (SD 7.4) vs 38° (SD 5.6)) (p = 0.032). We did not have any case of acetabular or femoral loosening at the time of the last follow-up. We had two patients with successful two-stage revision for infection with overall eight-year survival rate was 95.2% (95% CI 86.6% to 100%) with revision for any reason at a median (IQR) duration of follow-up 50 months (16 to 87) months following THA. Conclusion. Delayed cementless acetabular THA in patients with previous failed acetabular fracture treatments produces good clinical outcomes (PROMS) with excellent survivorship, despite the technically demanding nature of the procedure. The initial fracture treatment does not influence the outcome of delayed THA. In selected cases of acetabular fractures (either nondisplaced or with secondary congruency), the initial nonoperative treatment neither resulted in large acetabular defects nor required additional acetabular reconstruction at the time of THA. Cite this article: Bone Jt Open 2021;2(12):1067–1074

Aims. Several artificial bone grafts have been developed but fail to achieve anticipated osteogenesis due to their insufficient neovascularization capacity and periosteum support. This study aimed to develop a vascularized bone-periosteum construct (VBPC) to provide better angiogenesis and osteogenesis for bone regeneration. Methods. A total of 24 male New Zealand white rabbits were divided into four groups according to the experimental materials. Allogenic adipose-derived mesenchymal stem cells (AMSCs) were cultured and seeded evenly in the collagen/chitosan sheet to form cell sheet as periosteum. Simultaneously, allogenic AMSCs were seeded onto alginate beads and were cultured to differentiate to endothelial-like cells to form vascularized bone construct (VBC). The cell sheet was wrapped onto VBC to create a vascularized bone-periosteum construct (VBPC). Four different experimental materials – acellular construct, VBC, non-vascularized bone-periosteum construct, and VBPC – were then implanted in bilateral L4-L5 intertransverse space. At 12 weeks post-surgery, the bone-forming capacities were determined by CT, biomechanical testing, histology, and immunohistochemistry staining analyses. Results. At 12 weeks, the VBPC group significantly increased new bone formation volume compared with the other groups. Biomechanical testing demonstrated higher torque strength in the VBPC group. Notably, the haematoxylin and eosin, Masson’s trichrome, and immunohistochemistry-stained histological results revealed that VBPC promoted neovascularization and new bone formation in the spine fusion areas. Conclusion. The tissue-engineered VBPC showed great capability in promoting angiogenesis and osteogenesis in vivo. It may provide a novel approach to create a superior blood supply and nutritional environment to overcome the deficits of current artificial bone graft substitutes. Cite this article: Bone Joint Res 2023;12(12):722–733

Aims. Brace treatment is the cornerstone of managing developmental dysplasia of the hip (DDH), yet there is a lack of evidence-based treatment protocols, which results in wide variations in practice. To resolve this, we have developed a comprehensive nonoperative treatment protocol conforming to published consensus principles, with well-defined a priori criteria for inclusion and successful treatment. Methods. This was a single-centre, prospective, longitudinal cohort study of a consecutive series of infants with ultrasound-confirmed DDH who underwent a comprehensive nonoperative brace management protocol in a unified multidisciplinary clinic between January 2012 and December 2016 with five-year follow-up radiographs. The radiological outcomes were acetabular index-lateral edge (AI-L), acetabular index-sourcil (AI-S), centre-edge angle (CEA), acetabular depth ratio (ADR), International Hip Dysplasia Institute (IHDI) grade, and evidence of avascular necrosis (AVN). At five years, each hip was classified as normal (< 1 SD), borderline dysplastic (1 to 2 SDs), or dysplastic (> 2 SDs) based on validated radiological norm-referenced values. Results. Of 993 infants assessed clinically and sonographically, 21% (212 infants, 354 abnormal hips) had DDH and were included. Of these, 95% (202 infants, 335 hips) successfully completed bracing, and 5% (ten infants, 19 hips) failed bracing due to irreducible hip(s). The success rate of bracing for unilateral dislocations was 88% (45/51 infants) and for bilateral dislocations 83% (20/24 infants). The femoral nerve palsy rate was 1% (2/212 infants). At five-year follow-up (mean 63 months (SD 5.9; 49 to 83)) the prevalence of residual dysplasia after successful brace treatment was 1.6% (5/312 hips). All hips were IHDI grade I and none had AVN. Four children (4/186; 2%) subsequently underwent surgery for residual dysplasia. Conclusion. Our comprehensive protocol for nonoperative treatment of infant DDH has shown high rates of success and extremely low rates of residual dysplasia at a mean age of five years. Cite this article: Bone Joint J 2023;105-B(8):935–942

Aims. The aim of this study was to compare a bicruciate-retaining (BCR) total knee arthroplasty (TKA) with a posterior cruciate-retaining (CR) TKA design in terms of kinematics, measured using fluoroscopy and stability as micromotion using radiostereometric analysis (RSA). Methods. A total of 40 patients with end-stage osteoarthritis were included in this randomized controlled trial. All patients performed a step-up and lunge task in front of a monoplane fluoroscope one year postoperatively. Femorotibial contact point (CP) locations were determined at every flexion angle and compared between the groups. RSA images were taken at baseline, six weeks, three, six, 12, and 24 months postoperatively. Clinical and functional outcomes were compared postoperatively for two years. Results. The BCR-TKA demonstrated a kinematic pattern comparable to the natural knee’s screw-home mechanism in the step-up task. In the lunge task, the medial CP of the BCR-TKA was more anterior in the early flexion phase, while laterally the CP was more posterior during the entire movement cycle. The BCR-TKA group showed higher tibial migration. No differences were found for the clinical and functional outcomes. Conclusion. The BCR-TKA shows a different kinematic pattern in early flexion/late extension compared to the CR-TKA. The difference between both implants is mostly visible in the flexion phase in which the anterior cruciate ligament is effective; however, both designs fail to fully replicate the motion of a natural knee. The higher migration of the BCR-TKA was concerning and highlights the importance of longer follow-up. Cite this article: Bone Joint J 2023;105-B(1):35–46

Aims. The aims of this study were to determine the incidence and factors for developing periprosthetic joint infection (PJI) following hemiarthroplasty (HA) for hip fracture, and to evaluate treatment outcome and identify factors associated with treatment outcome. Methods. A retrospective review was performed of consecutive patients treated for HA PJI at a tertiary referral centre with a mean 4.5 years’ follow-up (1.6 weeks to 12.9 years). Surgeries performed included debridement, antibiotics, and implant retention (DAIR) and single-stage revision. The effect of different factors on developing infection and treatment outcome was determined. Results. A total of 1,984 HAs were performed during the study period, and 44 sustained a PJI (2.2%). Multiple logistic regression analysis revealed that a higher CCI score (odds ratio (OR) 1.56 (95% confidence interval (CI) 1.117 to 2.187); p = 0.003), peripheral vascular disease (OR 11.34 (95% CI 1.897 to 67.810); p = 0.008), cerebrovascular disease (OR 65.32 (95% CI 22.783 to 187.278); p < 0.001), diabetes (OR 4.82 (95% CI 1.903 to 12.218); p < 0.001), moderate-to-severe renal disease (OR 5.84 (95% CI 1.116 to 30.589); p = 0.037), cancer without metastasis (OR 6.42 (95% CI 1.643 to 25.006); p = 0.007), and metastatic solid tumour (OR 15.64 (95% CI 1.499 to 163.087); p = 0.022) were associated with increasing PJI risk. Upon final follow-up, 17 patients (38.6%) failed initial treatment and required further surgery for HA PJI. One-year mortality was 22.7%. Factors associated with treatment outcome included lower preoperative Hgb level (97.9 g/l (SD 11.4) vs 107.0 g/l (SD 16.1); p = 0.009), elevated CRP level (99.1 mg/l (SD 63.4) vs 56.6 mg/l (SD 47.1); p = 0.030), and type of surgery. There was lower chance of success with DAIR (42.3%) compared to revision HA (66.7%) or revision with conversion to total hip arthroplasty (100%). Early-onset PJI (≤ six weeks) was associated with a higher likelihood of treatment failure (OR 3.5 (95% CI 1.2 to 10.6); p = 0.007) along with patients treated by a non-arthroplasty surgeon (OR 2.5 (95% CI 1.2 to 5.3); p = 0.014). Conclusion. HA PJI initially treated with DAIR is associated with poor chances of success and its value is limited. We strongly recommend consideration of a single-stage revision arthroplasty with cemented components. Cite this article: Bone Jt Open 2022;3(12):924–932

Aims. Prophylactic antibiotic regimens for elective primary total hip and knee arthroplasty vary widely across hospitals and trusts in the UK. This study aimed to identify antibiotic prophylaxis regimens currently in use for elective primary arthroplasty across the UK, establish variations in antibiotic prophylaxis regimens and their impact on the risk of periprosthetic joint infection (PJI) in the first-year post-index procedure, and evaluate adherence to current international consensus guidance. Methods. The guidelines for the primary and alternative recommended prophylactic antibiotic regimens in clean orthopaedic surgery (primary arthroplasty) for 109 hospitals and trusts across the UK were sought by searching each trust and hospital’s website (intranet webpages), and by using the MicroGuide app. The mean cost of each antibiotic regimen was calculated using price data from the British National Formulary (BNF). Regimens were then compared to the 2018 Philadelphia Consensus Guidance, to evaluate adherence to international guidance. Results. The primary choice and dosing of the prophylactic antimicrobial regimens varied widely. The two most used regimens were combined teicoplanin and gentamicin, and cefuroxime followed by two or three doses of cefuroxime eight-hourly, recommended by 24 centres (22.02%) each. The alternative choice and dosing of the prophylactic antimicrobial regimen also varied widely across the 83 centres with data available. Prophylaxis regimens across some centres fail to cover the likeliest causes of surgical site infection (SSI). Five centres (4.59%) recommend co-amoxiclav, which confers no Staphylococcus coverage, while 33 centres (30.28%) recommend cefuroxime, which confers no Enterococcus coverage. Limited adherence to 2018 Philadelphia Consensus Guidance was observed, with 67 centres (61.50%) not including a cephalosporin in their guidance. Conclusion. This analysis of guidance on antimicrobial prophylaxis in primary arthroplasty across 109 hospitals and trusts in the UK has identified widespread variation in primary and alternative antimicrobial regimens currently recommended. Cite this article: Bone Jt Open 2023;4(10):742–749

Aims. Tissue inhibitors of metalloproteinases (TIMPs) are the endogenous inhibitors of the zinc-dependent matrix metalloproteinases (MMP) and A disintegrin and metalloproteinases (ADAM) involved in extracellular matrix modulation. The present study aims to develop the TIMPs as biologics for osteoclast-related disorders. Methods. We examine the inhibitory effect of a high affinity, glycosyl-phosphatidylinositol-anchored TIMP variant named ‘T1. PrαTACE. ’ on receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation. Results. Osteoclast progenitor cells transduced with T1. PrαTACE. failed to form tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts or exhibit bone-resorbing activity following treatment with RANKL. At the messenger RNA level, T1. PrαTACE. strongly attenuated expression of key osteoclast marker genes that included TRAP, cathepsin K, osteoclast stimulatory transmembrane protein (OC-STAMP), dendritic cell-specific transmembrane protein (DC-STAMP), osteoclast-associated receptor (OSCAR), and ATPase H. +. -transporting V0 subunit d2 (ATP6V0D2) by blocking autoamplification of nuclear factor of activated T cells 1 (NFATc1), the osteoclastogenic transcription factor. T1. PrαTACE. selectively extended p44/42 mitogen-activated protein kinase activation, an action that may have interrupted terminal differentiation of osteoclasts. Inhibition studies with broad-spectrum hydroxamate inhibitors confirmed that the anti-resorptive activity of T1. PrαTACE. was not reliant on its metalloproteinase-inhibitory activity. Conclusion. T1. PrαTACE. disrupts the RANKL-NFATc1 signalling pathway, which leads to osteoclast dysfunction. As a novel candidate in the prevention of osteoclastogenesis, the TIMP could potentially be developed for the treatment of osteoclast-related disorders such as osteoporosis. Cite this article: Bone Joint Res 2022;11(11):763–776

Aims. Evidence exists of a consistent decline in the value and time that medical schools place upon their undergraduate orthopaedic placements. This limited exposure to trauma and orthopaedics (T&O) during medical school will be the only experience in the speciality for the majority of doctors. This review aims to provide an overview of undergraduate orthopaedic training in the UK. Methods. This review summarizes the relevant literature from the last 20 years in the UK. Articles were selected from database searches using MEDLINE, EMBASE, ERIC, Cochrane, and Web of Science. A total of 16 papers met the inclusion criteria. Results. The length of exposure to T&O is declining; the mean total placement duration of two to three weeks is significantly less than the four- to six-week minimum advised by most relevant sources. The main teaching methods described in the literature included didactic lectures, bedside teaching, and small group case-based discussions. Students preferred interactive, blended learning teaching styles over didactic methods. This improvement in satisfaction was reflected in improvements in student assessment scores. However, studies failed to assess competencies in clinical skills and examinations, which is consistent with the opinions of UK foundation year doctors, approximately 40% of whom report a “poor” understanding of orthopaedics. Furthermore, the majority of UK doctors are not exposed to orthopaedics at the postgraduate level, which only serves to amplify the disparity between junior and generalist knowledge, and the standards expected by senior colleagues and professional bodies. Conclusion. There is a deficit in undergraduate orthopaedic training within the UK which has only worsened in the last 20 years, leaving medical students and foundation doctors with a potentially significant lack of orthopaedic knowledge. Cite this article: Bone Jt Open 2022;3(7):549–556

Aims. This study was performed to explore the effect of melatonin on pyroptosis in nucleus pulposus cells (NPCs) and the underlying mechanism of that effect. Methods. This experiment included three patients diagnosed with lumbar disc herniation who failed conservative treatment. Nucleus pulposus tissue was isolated from these patients when they underwent surgical intervention, and primary NPCs were isolated and cultured. Western blotting, reverse transcription polymerase chain reaction, fluorescence staining, and other methods were used to detect changes in related signalling pathways and the ability of cells to resist pyroptosis. Results. Western blot analysis confirmed the expression of cleaved CASP-1 and melatonin receptor (MT-1A-R) in NPCs. The cultured NPCs were identified by detecting the expression of CD24, collagen type II, and aggrecan. After treatment with hydrogen peroxide, the pyroptosis-related proteins NLR family pyrin domain containing 3 (NLRP3), cleaved CASP-1, N-terminal fragment of gasdermin D (GSDMD-N), interleukin (IL)-18, and IL-1β in NPCs were upregulated, and the number of propidium iodide (PI)-positive cells was also increased, which was able to be alleviated by pretreatment with melatonin. The protective effect of melatonin on pyroptosis was blunted by both the melatonin receptor antagonist luzindole and the nuclear factor erythroid 2–related factor 2 (Nrf2) inhibitor ML385. In addition, the expression of the transcription factor Nrf2 was up- or downregulated when the melatonin receptor was activated or blocked by melatonin or luzindole, respectively. Conclusion. Melatonin protects NPCs against reactive oxygen species-induced pyroptosis by upregulating the transcription factor Nrf2 via melatonin receptors. Cite this article: Bone Joint Res 2023;12(3):202–211

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

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. Prior cost-effectiveness analyses on osseointegrated prosthesis for transfemoral unilateral amputees have analyzed outcomes in non-USA countries using generic quality of life instruments, which may not be appropriate when evaluating disease-specific quality of life. These prior analyses have also focused only on patients who had failed a socket-based prosthesis. The aim of the current study is to use a disease-specific quality of life instrument, which can more accurately reflect a patient’s quality of life with this condition in order to evaluate cost-effectiveness, examining both treatment-naïve and socket refractory patients. Methods. Lifetime Markov models were developed evaluating active healthy middle-aged male amputees. Costs of the prostheses, associated complications, use/non-use, and annual costs of arthroplasty parts and service for both a socket and osseointegrated (OPRA) prosthesis were included. Effectiveness was evaluated using the questionnaire for persons with a transfemoral amputation (Q-TFA) until death. All costs and Q-TFA were discounted at 3% annually. Sensitivity analyses on those cost variables which affected a change in treatment (OPRA to socket, or socket to OPRA) were evaluated to determine threshold values. Incremental cost-effectiveness ratios (ICERs) were calculated. Results. For treatment-naïve patients, the lifetime ICER for OPRA was $279/quality-adjusted life-year (QALY). For treatment-refractory patients the ICER was $273/QALY. In sensitivity analysis, the variable thresholds that would affect a change in the course of treatment based on cost (from socket to OPRA), included the following for the treatment-naïve group: yearly replacement components for socket > $8,511; cost yearly replacement parts OPRA < $1,758; and for treatment-refractory group: yearly replacement component for socket of > $12,467. Conclusion. The use of the OPRA prosthesis in physically active transfemoral amputees should be considered as a cost-effective alternative in both treatment-naïve and treatment-refractory socket prosthesis patients. Disease-specific quality of life assessments such as Q-TFA are more sensitive when evaluating cost-effectiveness. Cite this article: Bone Jt Open 2024;5(3):218–226

Aims. The aim of this study was to compare the preinjury functional scores with the postinjury preoperative score and postoperative outcome scores following anterior cruciate ligament (ACL) reconstruction surgery (ACLR). Methods. We performed a prospective study on patients who underwent primary ACLR by a single surgeon at a single centre between October 2010 and January 2018. Preoperative preinjury scores were collected at time of first assessment after the index injury. Preoperative (pre- and post-injury), one-year, and two-year postoperative functional outcomes were assessed by using the Knee injury and Osteoarthritis Outcome Score (KOOS), Lysholm Knee Score, and Tegner Activity Scale. Results. We enrolled 308 males and 263 females of mean age 27 years (19 to 46). The mean preinjury and preoperative post-injury Lysholm Knee Scores were 94 (73 to 100) and 63 (25 to 85), respectively, while the respective mean scores at one and two years postoperatively were 84 (71 to 100) and 89 (71 to 100; p < 0.001). The mean Tegner preinjury and preoperative post-injury scores were 7 (3 to 9) and 3 (0 to 6), respectively, while the respective mean scores at one and two years postoperatively were 6 (1 to 8) and 6 (1 to 9) (p < 0.001). The mean KOOS scores at preinjury versus two years postoperatively were: symptoms (96 vs 84); pain (94 vs 87); activities of daily living (97 vs 91), sports and recreation function (84 vs 71), and quality of life (82 vs 69), respectively (p < 0.001). Conclusion. Functional scores improved following ACLR surgery at two years in comparison to preoperative post-injury scores. However, at two-year follow-up, the majority of patients failed to achieve their preinjury scores. The evaluation of ACLR outcomes needs to consider the preinjury scores rather than the immediate preoperative score that is usually collected. Cite this article: Bone Jt Open 2023;4(1):46–52