Aims. Infection complicating primary total knee arthroplasty (TKA) is a common reason for revision surgery, hospital readmission, patient morbidity, and mortality. Increasing incidence of methicillin-resistant Staphylococcus aureus (MRSA) is a particular concern. The use of vancomycin as prophylactic agent alone or in combination with cephalosporin has not demonstrated lower periprosthetic joint infection (PJI) rates, partly due to timing and dosing of intravenous (IV) vancomycin administration, which have proven important factors in effectiveness. This is a retrospective review of a consecutive series of primary TKAs examining incidence of PJI, adverse reactions, and complications using IV versus intraosseous (IO) vancomycin at 30-day, 90-day, and one-year follow-up. Methods. A retrospective review of 1,060 patients who underwent TKA between May 2016 to July 2020 was performed. There were 572 patients in the IV group and 488 in the IO group, with minimal 30 days of follow-up. Patients were followed up at regularly scheduled intervals (two, six, and 12 weeks). No differences between groups for age, sex, BMI, or baseline comorbidities existed. The IV group received an IV dose of 15 mg/kg vancomycin given over an hour preceding skin incision. The IO group received a 500 mg dose of vancomycin mixed in 150 ml of normal saline, injected into proximal tibia after tourniquet inflation, before skin incision. All patients received an additional dose of first generation cephalosporin. Evaluation included preoperative and postoperative serum creatinine values, tourniquet time, and adverse reactions attributable to vancomycin. Results. Incidence of PJI with minimum 90-day follow-up was 1.4% (eight knees) in the IV group and 0.22% (one knee) in IO group (p = 0.047). This preliminary report demonstrated an reduction in the incidence of infection in TKA using IO vancomycin combined with a first-generation cephalosporin. While the study suffers from limitations of a retrospective, multi-surgeon investigation, early findings are encouraging. Conclusion. IO delivery of vancomycin after tourniquet inflation is a safe and effective alternative to IV administration, eliminating the logistical challenges of timely dosing. Cite this article: Bone Joint J 2021;103-B(6 Supple A):13–17

The recently published Prophylactic Antibiotic Regimens In Tumor Surgery (PARITY) trial found no benefit in extending antibiotic prophylaxis from 24 hours to five days after endoprosthetic reconstruction for lower limb bone tumours. PARITY is the first randomized controlled trial in orthopaedic oncology and is a huge step forward in understanding antibiotic prophylaxis. However, significant gaps remain, including questions around antibiotic choice, particularly in the UK, where cephalosporins are avoided due to concerns of Clostridioides difficile infection. We present a review of the evidence for antibiotic choice, dosing, and timing, and a brief description of PARITY, its implication for practice, and the remaining gaps in our understanding. Cite this article: Bone Joint J 2023;105-B(8):850–856

Aims. Prompt and sufficient broad-spectrum empirical antibiotic treatment is key to preventing infection following open tibial fractures. Succeeding co-administration, we dynamically assessed the time for which vancomycin and meropenem concentrations were above relevant epidemiological cut-off (ECOFF) minimal inhibitory concentrations (T > MIC) in tibial compartments for the bacteria most frequently encountered in open fractures. Low and high MIC targets were applied: 1 and 4 µg/ml for vancomycin, and 0.125 and 2 µg/ml for meropenem. Methods. Eight pigs received a single dose of 1,000 mg vancomycin and 1,000 mg meropenem simultaneously over 100 minutes and 10 minutes, respectively. Microdialysis catheters were placed for sampling over eight hours in tibial cancellous bone, cortical bone, and adjacent subcutaneous adipose tissue. Venous blood samples were collected as references. Results. Across the targeted ECOFF values, vancomycin displayed longer T > MIC in all the investigated compartments in comparison to meropenem. For both drugs, cortical bone exhibited the shortest T > MIC. For the low MIC targets and across compartments, mean T > MIC ranged between 208 and 449 minutes (46% to 100%) for vancomycin and between 189 and 406 minutes (42% to 90%) for meropenem. For the high MIC targets, mean T > MIC ranged between 30 and 446 minutes (7% to 99%) for vancomycin and between 45 and 181 minutes (10% to 40%) for meropenem. Conclusion. The differences in the T > MIC between the low and high targets illustrate how the interpretation of these results is highly susceptible to the defined MIC target. To encompass any trauma, contamination, or individual tissue differences, a more aggressive dosing approach may be considered to achieve longer T > MIC in all the exposed tissues, and thereby lower the risk of acquiring an infection after open tibial fractures. Cite this article: Bone Joint Res 2022;11(2):112–120

Aims. The use of fluoroscopy in orthopaedic surgery creates risk of radiation exposure to surgeons. Appropriate personal protective equipment (PPE) can help mitigate this. The primary aim of this study was to assess if current radiation protection in orthopaedic trauma is safe. The secondary aims were to describe normative data of radiation exposure during common orthopaedic procedures, evaluate ways to improve any deficits in protection, and validate the use of electronic personal dosimeters (EPDs) in assessing radiation dose in orthopaedic surgery. Methods. Radiation exposure to surgeons during common orthopaedic trauma operations was prospectively assessed using EPDs and thermoluminescent dosimeters (TLDs). Normative data for each operation type were calculated and compared to recommended guidelines. Results. Current PPE appears to mitigate more than 90% of ionizing radiation in orthopaedic fluoroscopic procedures. There is a higher exposure to the inner thigh during seated procedures. EPDs provided results for individual procedures. Conclusion. PPE currently used by surgeons in orthopaedic trauma theatre adequately reduces radiation exposure to below recommended levels. Normative data per trauma case show specific anatomical areas of higher exposure, which may benefit from enhanced radiation protection. EPDs can be used to assess real-time radiation exposure in orthopaedic surgery. There may be a role in future medical wearables for orthopaedic surgeons. Cite this article: Bone Jt Open 2022;3(11):907–912

Aims. Ankle fracture fixation is commonly performed by junior trainees. Simulation training using cadavers may shorten the learning curve and result in a technically superior surgical performance. Methods. We undertook a preliminary, pragmatic, single-blinded, multicentre, randomized controlled trial of cadaveric simulation versus standard training. Primary outcome was fracture reduction on postoperative radiographs. Results. Overall, 139 ankle fractures were fixed by 28 postgraduate year three to five trainee surgeons (mean age 29.4 years; 71% males) during ten months' follow-up. Under the intention-to-treat principle, a technically superior fixation was performed by the cadaveric-trained group compared to the standard-trained group, as measured on the first postoperative radiograph against predefined acceptability thresholds. The cadaveric-trained group used a lower intraoperative dose of radiation than the standard-trained group (mean difference 0.011 Gym. 2. , 95% confidence interval 0.003 to 0.019; p = 0.009). There was no difference in procedure time. Conclusion. Trainees randomized to cadaveric training performed better ankle fracture fixations and irradiated patients less during surgery compared to standard-trained trainees. This effect, which was previously unknown, is likely to be a consequence of the intervention. Further study is required. Cite this article: Bone Jt Open 2023;4(8):594–601

Aims. The aim of this study was to identify the effect of the manufacturing characteristics of polyethylene acetabular liners on the survival of cementless and hybrid total hip arthroplasty (THA). Methods. Prospective cohort study using linked National Joint Registry (NJR) and manufacturer data. The primary endpoint was revision for aseptic loosening. Cox proportional hazard regression was the primary analytical approach. Manufacturing variables included resin type, crosslinking radiation dose, terminal sterilization method, terminal sterilization radiation dose, stabilization treatment, total radiation dose, packaging, and face asymmetry. Total radiation dose was further divided into G1 (no radiation), G2 (> 0 Mrad to < 5 Mrad), G3 (≥ 5 Mrad to < 10 Mrad), and G4 (≥ 10 Mrad). Results. A total of 5,329 THAs were revised, 1,290 of which were due to aseptic loosening. Total radiation dose, face asymmetry, and stabilization treatments were found to significantly affect implant survival. G1 had the highest revision risk for any reason and for aseptic loosening and G3 and G4 the lowest. Compared with G1, the adjusted hazard ratio for G2 was 0.74 (95% confidence interval (CI) 0.64 to 0.86), G3 was 0.36 (95% CI 0.30 to 0.43), and G4 was 0.38 (95% CI 0.31 to 0.47). The cumulative incidence of revision for aseptic loosening at 12 years was 0.52 and 0.54 per 100 THAs for G3 and G4, respectively, compared with 1.95 per 100 THAs in G1. Asymmetrical liners had a lower revision risk due to aseptic loosening and reasons other than aseptic loosening compared with symmetric (flat) liners. In G3 and G4, stabilization with vitamin E and heating above melting point performed best. Conclusion. Polyethylene liners with a total radiation dose of ≥ 5 Mrad, an asymmetrical liner face, and stabilization with heating above the melting point demonstrate best survival. Cite this article: Bone Joint J 2020;102-B(1):90–101

Aims. Blood transfusion and postoperative anaemia are complications of total knee arthroplasty (TKA) that are associated with substantial healthcare costs, morbidity, and mortality. There are few data from large datasets on the risk factors for these complications. Methods. We retrospectively reviewed the records of TKA patients from a single tertiary care institution from February 2016 to December 2020. There were a total of 14,901 patients in this cohort with a mean age of 67.9 years (SD 9.2), and 5,575 patients (37.4%) were male. Outcomes included perioperative blood transfusion and postoperative anaemia, defined a priori as haemoglobin level < 10 g/dl measured on the first day postoperatively. In order to establish a preoperative haemoglobin cutoff, we investigated a preoperative haemoglobin level that would limit transfusion likelihood to ≤ 1% (13 g/dl) and postoperative anaemia likelihood to 4.1%. Risk factors were assessed through multivariable Poisson regression modelling with robust error variance. Results. In multivariable analyses, each gram of tranexamic acid reduced transfusion likelihood by 39% (adjusted risk ratio (ARR) 0.61 (95% confidence interval (CI) 0.47 to 0.78)). Risk factors associated with an increased risk of transfusion included operating time (ARR 2.07 (95% CI 1.54 to 2.77)) and drain use (ARR 1.73 (95% CI 1.34 to 2.24)). Conclusion. In this study, we found that increased tranexamic acid dosing, decreased operating time, and decreased drain use may reduce transfusions following TKA. We also established a single preoperative haemoglobin cutoff of 13 g/dl that could help minimize transfusions and reduce postoperative complete blood counts. Cite this article: Bone Joint J 2023;105-B(10):1086–1093

Aims. A growing number of fractures progress to delayed or nonunion, causing significant morbidity and socioeconomic impact. Localized delivery of stem cells and subcutaneous parathyroid hormone (PTH) has been shown individually to accelerate bony regeneration. This study aimed to combine the therapies with the aim of upregulating fracture healing. Methods. A 1.5 mm femoral osteotomy (delayed union model) was created in 48 female juvenile Wistar rats, aged six to nine months, and stabilized using an external fixator. At day 0, animals were treated with intrafracture injections of 1 × 10. 6. cells/kg bone marrow mesenchymal stem cells (MSCs) suspended in fibrin, daily subcutaneous injections of high (100 μg/kg) or low (25 μg/kg) dose PTH 1-34, or a combination of PTH and MSCs. A group with an empty gap served as a control. Five weeks post-surgery, the femur was excised for radiological, histomorphometric, micro-CT, and mechanical analysis. Results. Combination therapy treatment led to increased callus formation compared to controls. In the high-dose combination group there was significantly greater mineralized tissue volume and trabecular parameters compared to controls (p = 0.039). This translated to significantly improved stiffness (and ultimate load to failure (p = 0.049). The high-dose combination therapy group had the most significant improvement in mean modified Radiographic Union Score for Tibia fractures (RUST) compared to controls (13.8 (SD 1.3) vs 5.8 (SD 0.5)). All groups demonstrated significant increases in the radiological scores – RUST and Allen score – histologically compared to controls. Conclusion. We demonstrate the beneficial effect of localized MSC injections on fracture healing combined with low- or high-dose teriparatide, with efficacy dependent on PTH dose. Cite this article: Bone Joint Res 2021;10(10):659–667

Aims. To investigate the effect of polyethylene manufacturing characteristics and irradiation dose on the survival of cemented and reverse hybrid total hip arthroplasties (THAs). Methods. In this registry study, data from the National Joint Registry of England, Wales, Northern Ireland and the Isle of Man (NJR) were linked with manufacturing data supplied by manufacturers. The primary endpoint was revision of any component. Cox proportional hazard regression was a primary analytic approach adjusting for competing risk of death, patient characteristics, head composition, and stem fixation. Results. A total of 290,770 primary THAs were successfully linked with manufacturing characteristics. Overall 4,708 revisions were analyzed, 1,260 of which were due to aseptic loosening. Total radiation dose was identified as a risk factor and included in the Cox model. For statistical modelling of aseptic loosening, THAs were grouped into three categories: G1 (no radiation); G2 ( > 0 to < 5 Mrad); and G3 ( ≥ 5 Mrad). G1 had the worst survivorship. The Cox regression hazard ratio for revision due to aseptic loosening for G2 was 0.7 (95% confidence interval (CI) 0.58 to 0.83), and for G3 0.4 (95% CI 0.30 to 0.53). Male sex and uncemented stem fixation were associated with higher risk of revision and ceramic heads with lower risk. Conclusion. Polyethylene irradiation was associated with reduced risk of revision for aseptic loosening. Radiation doses of ≥ 5 Mrad were associated with a further reduction in risk. Cite this article: Bone Joint Res 2020;9(9):563–571

Objectives. Activation of the leptin pathway is closely correlated with human knee cartilage degeneration. However, the role of the long form of the leptin receptor (Ob-Rb) in cartilage degeneration needs further study. The aim of this study was to determine the effect of increasing the expression of Ob-Rb on chondrocytes using a lentiviral vector containing Ob-Rb. Methods. The medial and lateral cartilage samples of the tibial plateau from 12 osteoarthritis (OA) patients were collected. Ob-Rb messenger RNA (mRNA) was detected in these samples. The Ob-Rb-overexpressing chondrocytes and controls were treated with different doses of leptin for two days. The activation of the p53/p21 pathway and the number of senescence-associated β-galactosidase (SA-β-gal)-positive cells were evaluated. The mammalian target of rapamycin (mTOR) signalling pathway and autophagy were detected after the chondrocytes were treated with a high dose of leptin. Results. In total, 12 cases were found to have severe medial cartilage wear compared with the lateral cartilage. Immunofluorescence showed that the expression of Ob-Rb in the medial cartilage of the tibial plateau was high. High levels of leptin led to cell cycle arrest and inhibited autophagy. After overexpression of Ob-Rb, the physiological dose of leptin induced cell senescence in the chondrocytes. High doses of leptin inhibited autophagy by activating the mTOR signalling pathway. Blockade of the mTOR signalling pathway could restore autophagy and partially reverse senescence induced by leptin in chondrocytes. Conclusion. In summary, the present study demonstrated that high doses of leptin induce cell senescence by activating the mTOR pathway in chondrocytes from OA cartilage. Highly expressed Ob-Rb accelerates chondrocyte senescence by activating the leptin pathway in OA. Cite this article: X. Zhao, P. Huang, G. Li, L. Zhendong, G. Hu, Q. Xu. Activation of the leptin pathway by high expression of the long form of the leptin receptor (Ob-Rb) accelerates chondrocyte senescence in osteoarthritis. Bone Joint Res 2019;8:425–436. DOI: 10.1302/2046-3758.89.BJR-2018-0325.R2

Aims. To evaluate if, for orthopaedic trainees, additional cadaveric simulation training or standard training alone yields superior radiological and clinical outcomes in patients undergoing dynamic hip screw (DHS) fixation or hemiarthroplasty for hip fracture. Methods. This was a preliminary, pragmatic, multicentre, parallel group randomized controlled trial in nine secondary and tertiary NHS hospitals in England. Researchers were blinded to group allocation. Overall, 40 trainees in the West Midlands were eligible: 33 agreed to take part and were randomized, five withdrew after randomization, 13 were allocated cadaveric training, and 15 were allocated standard training. The intervention was an additional two-day cadaveric simulation course. The control group received standard on-the-job training. Primary outcome was implant position on the postoperative radiograph: tip-apex distance (mm) (DHS) and leg length discrepancy (mm) (hemiarthroplasty). Secondary clinical outcomes were procedure time, length of hospital stay, acute postoperative complication rate, and 12-month mortality. Procedure-specific secondary outcomes were intraoperative radiation dose (for DHS) and postoperative blood transfusion requirement (hemiarthroplasty). Results. Eight female (29%) and 20 male trainees (71%), mean age 29.4 years, performed 317 DHS operations and 243 hemiarthroplasties during ten months of follow-up. Primary analysis was a random effect model with surgeon-level fixed effects of patient condition, patient age, and surgeon experience, with a random intercept for surgeon. Under the intention-to-treat principle, for hemiarthroplasty there was better implant position in favour of cadaveric training, measured by leg length discrepancy ≤ 10 mm (odds ratio (OR) 4.08 (95% confidence interval (CI) 1.17 to 14.22); p = 0.027). There were significantly fewer postoperative blood transfusions required in patients undergoing hemiarthroplasty by cadaveric-trained compared to standard-trained surgeons (OR 6.00 (95% CI 1.83 to 19.69); p = 0.003). For DHS, there was no significant between-group difference in implant position as measured by tip-apex distance ≤ 25 mm (OR 6.47 (95% CI 0.97 to 43.05); p = 0.053). No between-group differences were observed for any secondary clinical outcomes. Conclusion. Trainees randomized to additional cadaveric training performed hip fracture fixation with better implant positioning and fewer postoperative blood transfusions in hemiarthroplasty. This effect, which was previously unknown, may be a consequence of the intervention. Further study is required. Cite this article: Bone Jt Open 2023;4(8):602–611

Objectives. Prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasty. Non-contact induction heating of metal implants is a new and emerging treatment for PJI. However, there may be concerns for potential tissue necrosis. It is thought that segmental induction heating can be used to control the thermal dose and to limit collateral thermal injury to the bone and surrounding tissues. The purpose of this study was to determine the thermal dose, for commonly used metal implants in orthopaedic surgery, at various distances from the heating centre (HC). Methods. Commonly used metal orthopaedic implants (hip stem, intramedullary nail, and locking compression plate (LCP)) were heated segmentally using an induction heater. The thermal dose was expressed in cumulative equivalent minutes at 43°C (CEM43) and measured with a thermal camera at several different distances from the HC. A value of 16 CEM43 was used as the threshold for thermal damage in bone. Results. Despite high thermal doses at the HC (7161 CEM43 to 66 640 CEM43), the thermal dose at various distances from the HC was lower than 16 CEM43 for the hip stem and nail. For the fracture plate without corresponding metal screws, doses higher than 16 CEM43 were measured up to 5 mm from the HC. Conclusion. Segmental induction heating concentrates the thermal dose at the targeted metal implant areas and minimizes collateral thermal injury by using the non-heated metal as a heat sink. Implant type and geometry are important factors to consider, as they influence dissipation of heat and associated collateral thermal injury. Cite this article: B. G. Pijls, I. M. J. G. Sanders, E. J. Kuijper, R. G. H. H. Nelissen. Segmental induction heating of orthopaedic metal implants. Bone Joint Res 2018;7:609–619. DOI: 10.1302/2046-3758.711.BJR-2018-0080.R1

Aims. Tranexamic acid (TXA) has been shown to reduce blood loss and transfusion requirements in patients undergoing orthopaedic surgery. There remains a lack of prospective evidence for the use of TXA in patients undergoing periacetabular osteotomy (PAO). The purpose of this study was to determine if intravenous (IV) TXA is effective in reducing calculated blood loss and transfusions after PAO. Methods. This was a single-centre prospective double-blind placebo-controlled randomized trial of 81 patients aged 12 to 45 years undergoing elective PAO by a single surgeon. The intervention group (n = 40) received two doses of IV TXA of a maximum 1 g in each dose; the control group (n = 41) received two doses of 50 ml 0.9% saline IV. The primary outcome was perioperative calculated blood loss. Secondary outcomes included allogenic transfusions and six-week postoperative complications. Results. There were no differences in demographics or intraoperative variables between study groups. The TXA group demonstrated lower mean calculated blood loss (1,265 ml, (SD 321) vs 1,515 ml, (SD 394); p = 0.002) and lower frequency of allogenic transfusion (10%/n = 4 vs 37%/n = 15; p = 0.008). Regression analyses associated TXA use with significant reductions in calculated blood loss (p < 0.001) and transfusion (p = 0.007) after adjusting for age, sex, body mass index, preoperative haemoglobin, cell-saver volume, intraoperative mean arterial blood pressure, and operating time. No patients suffered venous thromboembolic complications. Conclusion. In this trial, IV TXA decreased postoperative calculated blood loss by 293 ml and reduced the frequency of allogenic transfusions by 73% (37% vs 10%) following PAO. TXA may be safe and effective for reducing blood loss in patients undergoing PAO. Cite this article: Bone Joint J 2020;102-B(9):1151–1157

Aims. A local injection may be used as an early option in the treatment of Morton’s neuroma, and can be performed using various medications. The aim of this study was to compare the effects of injections of hyaluronic acid compared with corticosteroid in the treatment of this condition. Methods. A total of 91 patients were assessed for this trial, of whom 45 were subsequently included and randomized into two groups. One patient was lost to follow-up, leaving 22 patients (24 feet) in each group. The patients in the hyaluronic acid group were treated with three ultrasound-guided injections (one per week) of hyaluronic acid (Osteonil Plus). Those in the corticosteroid group were treated with three ultrasound-guided injections (also one per week) of triamcinolone (Triancil). The patients were evaluated before treatment and at one, three, six, and 12 months after treatment. The primary outcome measure was the visual analogue scale for pain (VAS). Secondary outcome measures included the American Orthopaedic Foot and Ankle Society (AOFAS) score, and complications. Results. Both groups showed significant improvement in VAS and AOFAS scores (p < 0.05) after 12 months. The corticosteroid group had a significantly greater reduction in VAS and increase in AOFAS scores compared with the hyaluronic acid group, at one, three, and six months, but with no significant difference at 12 months. There were no complications in the hyaluronic acid group. There were minor local complications in six patients (six feet) (25.0%) in the corticosteroid group, all with discolouration of the skin at the site of the injection. These minor complications might have been due to the three weekly injections of a relatively high dose of corticosteroid. No patient subsequently underwent excision of the neuroma. Conclusion. An ultrasound-guided corticosteroid injection showed statistically significantly better functional and pain outcomes than an ultrasound-guided injection of hyaluronic acid for the treatment of a Morton’s neuroma at many timepoints. Thus, a corticosteroid injection should be regarded as a primary option in the treatment of these patients, and the only indication for an injection of hyaluronic acid might be in patients in whom corticosteroid is contraindicated. Cite this article: Bone Joint J 2024;106-B(10):1093–1099

Aims. Autologous chondrocyte implantation (ACI) is a promising treatment for articular cartilage degeneration and injury; however, it requires a large number of human hyaline chondrocytes, which often undergo dedifferentiation during in vitro expansion. This study aimed to investigate the effect of suramin on chondrocyte differentiation and its underlying mechanism. Methods. Porcine chondrocytes were treated with vehicle or various doses of suramin. The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN); COL1A1; COL10A1; SRY-box transcription factor 9 (SOX9); nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX); interleukin (IL)-1β; tumour necrosis factor alpha (TNFα); IL-8; and matrix metallopeptidase 13 (MMP-13) in chondrocytes at both messenger RNA (mRNA) and protein levels was determined by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blot. In addition, the supplementation of suramin to redifferentiation medium for the culture of expanded chondrocytes in 3D pellets was evaluated. Glycosaminoglycan (GAG) and collagen production were evaluated by biochemical analyses and immunofluorescence, as well as by immunohistochemistry. The expression of reactive oxygen species (ROS) and NOX activity were assessed by luciferase reporter gene assay, immunofluorescence analysis, and flow cytometry. Mutagenesis analysis, Alcian blue staining, reverse transcriptase polymerase chain reaction (RT-PCR), and western blot assay were used to determine whether p67. phox. was involved in suramin-enhanced chondrocyte phenotype maintenance. Results. Suramin enhanced the COL2A1 and ACAN expression and lowered COL1A1 synthesis. Also, in 3D pellet culture GAG and COL2A1 production was significantly higher in pellets consisting of chondrocytes expanded with suramin compared to controls. Surprisingly, suramin also increased ROS generation, which is largely caused by enhanced NOX (p67. phox. ) activity and membrane translocation. Overexpression of p67. phox. but not p67. phox. AD (deleting amino acid (a.a) 199 to 212) mutant, which does not support ROS production in chondrocytes, significantly enhanced chondrocyte phenotype maintenance, SOX9 expression, and AKT (S473) phosphorylation. Knockdown of p67. phox. with its specific short hairpin (sh) RNA (shRNA) abolished the suramin-induced effects. Moreover, when these cells were treated with the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) inhibitor LY294002 or shRNA of AKT1, p67. phox. -induced COL2A1 and ACAN expression was significantly inhibited. Conclusion. Suramin could redifferentiate dedifferentiated chondrocytes dependent on p67. phox. activation, which is mediated by the PI3K/AKT/SOX9 signalling pathway. Cite this article: Bone Joint Res 2022;11(10):723–738

Aims. Continuous local antibiotic perfusion (CLAP) has recently attracted attention as a new drug delivery system for orthopaedic infections. CLAP is a direct continuous infusion of high-concentration gentamicin (1,200 μg/ml) into the bone marrow. As it is a new system, its influence on the bone marrow is unknown. This study aimed to examine the effects of high-concentration antibiotics on human bone tissue-derived cells. Methods. Cells were isolated from the bone tissue grafts collected from six patients using the Reamer-Irrigator-Aspirator system, and exposed to different gentamicin concentrations. Live cells rate, apoptosis rate, alkaline phosphatase (ALP) activity, expression of osteoblast-related genes, mineralization potential, and restoration of cell viability and ALP activity were examined by in vitro studies. Results. The live cells rate (the ratio of total number of cells in the well plate to the absorbance-measured number of live cells) was significantly decreased at ≥ 500 μg/ml of gentamicin on day 14; apoptosis rate was significantly increased at ≥ 750 μg/ml, and ALP activity was significantly decreased at ≥ 750 μg/ml. Real-time reverse transcription-polymerase chain reaction results showed no significant decrease in the ALP and activating transcription factor 4 transcript levels at ≥ 1,000 μg/ml on day 7. Mineralization potential was significantly decreased at all concentrations. Restoration of cell viability was significantly decreased at 750 and 1,000 μg/ml on day 21 and at 500 μg/ml on day 28, and ALP activity was significantly decreased at 500 μg/ml on day 28. Conclusion. Our findings suggest that the exposure concentration and duration of antibiotic administration during CLAP could affect cell functions. However, further in vivo studies are needed to determine the optimal dose in a clinical setting. Cite this article: Bone Joint Res 2024;13(3):91–100

Aims. The aim of this study was to identify the most effective regimen of multiple doses of oral tranexamic acid (TXA) in achieving maximum reduction of blood loss in total knee arthroplasty (TKA). Patients and Methods. In this randomized controlled trial, 200 patients were randomized to receive a single dose of 2.0 g of TXA orally two hours preoperatively (group A), a single dose of TXA followed by 1.0 g orally three hours postoperatively (group B), a single dose of TXA followed by 1.0 g three and nine hours postoperatively (group C), or a single dose of TXA followed by 1.0 g orally three, nine, and 15 hours postoperatively (group D). All patients followed a routine enhanced-recovery protocol. The primary outcome measure was the total blood loss. Secondary outcome measures were hidden blood loss (HBL), reduction in the level of haemoglobin, the rate of transfusion and adverse events. Results. Groups C (661.1 ml, . sd. 262.4) and D (597.7 ml, . sd. 219.6) had significantly lower mean total blood loss compared with groups A and B. The mean HBL was significantly lower in groups B (699.2 ml), C (533.1 ml) and D (469.9 ml) than in group A (p = 0.006, p < 0.001, and p < 0.001, respectively). Groups C (2.22 ml, . sd. 0.91) and D (2.04 ml, . sd. 0.95) had a lower reduction in the level of haemoglobin than groups A and B. However, there were no differences between groups C and D in relation to the three parameters. Conclusion. The addition of two or three postoperative doses of TXA to one preoperative dose produced a significant reduction in blood loss. The two-dose postoperative regimen is the least necessary regimen for clinical efficacy in primary unilateral TKA. The three-dose regimen produced maximum reduction of blood loss. Cite this article: Bone Joint J 2018;100-B:1025–32

Aims. Tranexamic acid (TXA) is proven to reduce blood loss following total knee arthroplasty (TKA), but there are limited data on the impact of similar dosing regimens in revision TKA. The purpose of this multicentre randomized clinical trial was to determine the optimal regimen to maximize the blood-sparing properties of TXA in revision TKA. Patients and Methods. From six-centres, 233 revision TKAs were randomized to one of four regimens: 1 g of intravenous (IV) TXA given prior to the skin incision, a double-dose regimen of 1 g IV TXA given both prior to skin incision and at time of wound closure, a combination of 1 g IV TXA given prior to skin incision and 1 g of intraoperative topical TXA, or three doses of 1950 mg oral TXA given two hours preoperatively, six hours postoperatively, and on the morning of postoperative day one. Randomization was performed based on the type of revision procedure to ensure equivalent distribution among groups. Power analysis determined that 40 patients per group were necessary to identify a 1 g/dl difference in the reduction of haemoglobin postoperatively between groups with an alpha of 0.05 and power of 0.80. Per-protocol analysis involved regression analysis and two one-sided t-tests for equivalence. Results. In total, one patient withdrew, five did not undergo surgery, 16 were screening failures, and 25 did not receive the assigned treatment, leaving 186 patients for analysis. There was no significant difference in haemoglobin reduction among treatments (2.8 g/dl for single-dose IV TXA, 2.6 g/dl for double-dose IV TXA, 2.6 g/dl for combined IV/topical TXA, 2.9 g/dl for oral TXA; p = 0.38). Similarly, calculated blood loss (p = 0.65) and transfusion rates (p = 0.95) were not significantly different between groups. Equivalence testing assuming a 1 g/dl difference in haemoglobin change as clinically relevant showed that all possible pairings were statistically equivalent. Conclusion. Despite the higher risk of blood loss in revision TKA, all TXA regimens tested had equivalent blood-sparing properties. Surgeons should consider using the lowest effective dose and least costly TXA regimen in revision TKA. Cite this article: Bone Joint J 2019;101-B(Supple 7):10–16

Aims. The aim of this study was to quantify the risk of developing cancer from the exposure to radiation associated with surgery to correct limb deformities in children. Patients and Methods. A total of 35 children were studied. There were 19 girls and 16 boys. Their mean age was 11.9 years (2 to 18) at the time of surgery. Details of the radiological examinations were recorded during gradual correction using a Taylor Spatial Frame. The dose area product for each radiograph was obtained from the Computerised Radiology Information System database. The effective dose in millisieverts (mSv) was calculated using conversion coefficients for the anatomical area. The lifetime risk of developing cancer was calculated using government-approved Health Protection Agency reports, accounting for the age and gender of the child. Results. Correction was undertaken in five femurs, 18 tibiae, and 12 feet. The median duration of treatment was 45 months (11 to 118). The mean effective dose was 0.31 mSv (0.05 to 0.64) for the femur, 0.29 mSv (0.01 to 0.97) for the tibia, and 0.027 mSv (0.001 to 0.161) for the foot. The cumulative exposure gave ‘negligible’ risk in 26 children and ‘minimal’ risk in nine children, according to Public Health England categories. These results are below the mean annual background radiation in the United Kingdom. Conclusion. The lifetime attributable risk of developing cancer from repeated exposure to radiation was negligible or minimal in all children. This is the first study to quantify the exposure to radiation from serial radiographs in children with limb deformities who are treated surgically using circular external fixation, linking this to the risk of developing cancer. Cite this article: Bone Joint J 2019;101-B:241–245

Aims. Orthopaedic infection is a potentially serious complication of elective and emergency trauma and orthopaedic procedures, with a high associated burden of morbidity and cost. Optimization of vitamin D levels has been postulated to be beneficial in the prevention of orthopaedic infection. This study explores the role of vitamin D in orthopaedic infection through a systematic review of available evidence. Methods. A comprehensive search was conducted on databases including Medline and Embase, as well as grey literature such as Google Scholar and The World Health Organization Database. Pooled analysis with weighted means was undertaken. Results. Pooled analysis of four studies including 651 patients found the mean 25(OH)D level to be 50.7 nmol/l with a mean incidence of infection of 70%. There was a paucity of literature exploring prophylactic 25(OH)D supplementation on reducing orthopaedic infection, however, there was evidence of association between low 25(OH)D levels and increased incidence of orthopaedic infection. Conclusion. The results indicate a significant proportion of orthopaedic patients have low 25(OH]D levels, as well as an association between low 25(OH)D levels and orthopaedic infection, but more randomized controlled trials need to be conducted to establish the benefit of prophylactic supplementation and the optimum regimen by dose and time. Cite this article: Bone Jt Open 2021;2(9):721–727