We examined the effect on bone mineral density (BMD) of a single dose of 3 mg/kg of the bisphosphonate, pamidronate (Novartis) in distraction osteogenesis in immature rabbits.

Seventeen rabbits (9 control, 8 given pamidronate) were examined by dual-energy x-ray absorptiometry. There was a significant increase in the BMD in the pamidronate group compared with the control animals. The mean areal BMD (g/cm²) in the bone proximal and distal to the regenerate was increased by 40% and 39%, respectively, compared with the control group (p < 0.05). The BMD of the regenerate bone was increased by a mean of 43% (p < 0.05). There was an increase of 22% in the mean area of regenerate formed in the pamidronate group (p< 0.05).

Histological examination of bone in nine rabbits (5 control, 4 pamidronate) showed an increase in osteoblastic rimming and mineralisation of the regenerate, increased formation of bone around the pin sites and an increase in the cortical width of the bone adjacent to the regenerate in the rabbits given pamidronate.

Pamidronate had a markedly positive effect. It reduced the disuse osteoporosis normally associated with lengthening using an external fixator and increased the amount and density of the regenerate bone. Further study is required to examine the mechanical properties of the regenerate after the administration of pamidronate.

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

The October 2024 Research Roundup. 360. looks at: Fracture risk among stroke survivors according to post-stroke disability status and stroke type; Noise-induced hearing loss: should surgeons be wearing ear protection during primary total joint replacement?; Intravenous dexamethasone in hip arthroscopy can enhance recovery; Patient-reported outcomes following periprosthetic joint infection of the hip and knee: a longitudinal, prospective observational study; When should surgery take place after weight loss?; Which type of surgery is the hardest physically and mentally?

Prophylactic antibiotics are important in reducing the risk of periprosthetic joint infection (PJI) following total knee arthroplasty. Their effectiveness depends on the choice of antibiotic and the optimum timing of their administration, to ensure adequate tissue concentrations. Cephalosporins are typically used, but an increasing number of resistant organisms are causing PJI, leading to the additional use of vancomycin. There are difficulties, however, with the systemic administration of vancomycin including its optimal timing, due to the need for prolonged administration, and potential adverse reactions. Intraosseous regional administration distal to a tourniquet is an alternative and attractive mode of delivery due to the ease of obtaining intraosseous access. Many authors have reported the effectiveness of intraosseous prophylaxis in achieving higher concentrations of antibiotic in the tissues compared with intravenous administration, providing equal or enhanced prophylaxis while minimizing adverse effects. This annotation describes the technique of intraosseous administration of antibiotics and summarizes the relevant clinical literature to date. Cite this article: Bone Joint J 2023;105-B(11):1135–1139

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

The February 2024 Hip & Pelvis Roundup. 360. looks at: Trial of vancomycin and cefazolin as surgical prophylaxis in arthroplasty; Is preoperative posterior femoral neck tilt a risk factor for fixation failure? Cemented versus uncemented hemiarthroplasty for displaced intracapsular fractures of the hip; Periprosthetic fractures in larger hydroxyapatite-coated stems: are collared stems a better alternative for total hip arthroplasty?; Postoperative periprosthetic fracture following hip arthroplasty with a polished taper slip versus composite beam stem; Is oral tranexamic acid as good as intravenous?; Stem design and the risk of early periprosthetic femur fractures following THA in elderly patients; Does powered femoral broaching compromise patient safety in total hip arthroplasty?

The August 2024 Shoulder & Elbow Roundup. 360. looks at: Comparing augmented and nonaugmented locking-plate fixation for proximal humeral fractures in the elderly; Elevated five-year mortality following shoulder arthroplasty for fracture; Total intravenous anaesthesia with propofol reduces discharge times compared with inhaled general anaesthesia in shoulder arthroscopy: a randomized controlled trial; The influence of obesity on outcomes following arthroscopic rotator cuff repair; Humeral component version has no effect on outcomes following reverse total shoulder arthroplasty: a prospective, double-blinded, randomized controlled trial; What is a meaningful improvement after total shoulder arthroplasty by implant type, preoperative diagnosis, and sex?; The safety of corticosteroid injection prior to shoulder arthroplasty: a systematic review; Mortality and subsequent fractures of patients with olecranon fractures compared to other upper limb osteoporotic fractures

Aims. Methicillin-resistant Staphylococcus aureus (MRSA) can cause wound infections via a ‘Trojan Horse’ mechanism, in which neutrophils engulf intestinal MRSA and travel to the wound, releasing MRSA after apoptosis. The possible role of intestinal MRSA in prosthetic joint infection (PJI) is unknown. Methods. Rats underwent intestinal colonization with green fluorescent protein (GFP)-tagged MRSA by gavage and an intra-articular wire was then surgically implanted. After ten days, the presence of PJI was determined by bacterial cultures of the distal femur, joint capsule, and implant. We excluded several other possibilities for PJI development. Intraoperative contamination was excluded by culturing the specimen obtained from surgical site. Extracellular bacteraemia-associated PJI was excluded by comparing with the infection rate after intravenous injection of MRSA or MRSA-carrying neutrophils. To further support this theory, we tested the efficacy of prophylactic membrane-permeable and non-membrane-permeable antibiotics in this model. Results. After undergoing knee surgery eight or 72 hours after colonization, five out of 20 rats (25.0%) and two out of 20 rats (10.0%) developed PJI, respectively. Strikingly, 11 out of 20 rats (55.0%) developed PJI after intravenous injection of MRSA-carrying neutrophils that were isolated from rats with intestinal MRSA colonization. None of the rats receiving intravenous injections of MRSA developed PJI. These results suggest that intestinal MRSA carried by neutrophils could cause PJI in our rat model. Ten out of 20 (50.0%) rats treated with non-membrane-permeable gentamicin developed PJI, whereas only one out of 20 (5.0%) rats treated with membrane-permeable linezolid developed PJI. Conclusion. Neutrophils as carriers of intestinal MRSA may play an important role in PJI development. Cite this article:Bone Joint Res. 2020;9(4):152–161

Aims. Tranexamic acid (TXA) is now commonly used in major surgical operations including orthopaedics. The TRAC-24 randomized control trial (RCT) aimed to assess if an additional 24 hours of TXA postoperatively in primary total hip (THA) and total knee arthroplasty (TKA) reduced blood loss. Contrary to other orthopaedic studies to date, this trial included high-risk patients. This paper presents the results of a cost analysis undertaken alongside this RCT. Methods. TRAC-24 was a prospective RCT on patients undergoing TKA and THA. Three groups were included: Group 1 received 1 g intravenous (IV) TXA perioperatively and an additional 24-hour postoperative oral regime, Group 2 received only the perioperative dose, and Group 3 did not receive TXA. Cost analysis was performed out to day 90. Results. Group 1 was associated with the lowest mean total costs, followed by Group 2 and then Group 3. The differences between Groups 1 and 3 (-£797.77 (95% confidence interval -1,478.22 to -117.32) were statistically significant. Extended oral dosing reduced costs for patients undergoing THA but not TKA. The reduced costs in Groups 1 and 2 resulted from reduced length of stay, readmission rates, emergency department attendances, and blood transfusions. Conclusion. This study demonstrated significant cost savings when using TXA in primary THA or TKA. Extended oral dosing reduced costs further in THA but not TKA. Cite this article: Bone Jt Open 2022;3(7):536–542

Aims. Adenosine, lidocaine, and Mg. 2+. (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery. Methods. Male (n = 21) and female (n = 21) adult Sprague-Dawley rats were randomly divided into ALM or Saline control treatment groups. Three days after ACL rupture, animals underwent ACLR. An ALM or saline intravenous infusion was commenced prior to skin incision, and continued for one hour. An intra-articular bolus of ALM or saline was also administered prior to skin closure. Animals were monitored to 28 days, and joint function, pain, inflammatory markers, histopathology, and tissue repair markers were assessed. Results. Despite comparable knee function, ALM-treated males had reduced systemic inflammation, synovial fluid angiogenic and pro-inflammatory mediators, synovitis, and fat pad fibrotic changes, compared to controls. Within the ACL graft, ALM-treated males had increased expression of tissue repair markers, decreased inflammation, increased collagen organization, and improved graft-bone healing. In contrast to males, females had no evidence of persistent systemic inflammation. Compared to controls, ALM-treated females had improved knee extension, gait biomechanics, and elevated synovial macrophage inflammatory protein-1 alpha (MIP-1α). Within the ACL graft, ALM-treated females had decreased inflammation, increased collagen organization, and improved graft-bone healing. In articular cartilage of ALM-treated animals, matrix metalloproteinase (MMP)-13 expression was blunted in males, while in females repair markers were increased. Conclusion. At 28 days, ALM therapy reduces inflammation, augments tissue repair patterns, and improves joint function in a sex-specific manner. The study supports transition to human safety trials. Cite this article: Bone Joint Res 2024;13(6):279–293

Aims. The aim of this study was to determine the rate of indocyanine green (ICG) staining of bone and soft-tissue tumours, as well as the stability and accuracy of ICG fluorescence imaging in detecting tumour residuals during surgery for bone and soft-tissue tumours. Methods. ICG fluorescence imaging was performed during surgery in 34 patients with bone and soft-tissue tumours. ICG was administered intravenously at a dose of 2 mg/kg over a period of 60 minutes on the day prior to surgery. The tumour stain rate and signal-to-background ratio of each tumour were post hoc analyzed. After tumour resection, the tumour bed was scanned to locate sites with fluorescence residuals, which were subsequently inspected and biopsied. Results. The overall tumour stain rate was 88% (30/34 patients), and specific stain rates included 90% for osteosarcomas and 92% for giant cell tumours. For malignant tumours, the overall stain rate was 94%, while it was 82% for benign tumours. The ICG tumour stain was not influenced by different pathologies, such as malignant versus benign pathology, the reception (or lack thereof) of neoadjuvant chemotherapies, the length of time between drug administration and surgery, the number of doses of denosumab for patients with giant cell tumours, or the tumour response to neoadjuvant chemotherapy. The overall accuracy rate of successfully predicting tumour residuals using fluorescence was 49% (23/47 pieces of tissue). The accuracy rate after en bloc resection was significantly lower than that after piecemeal resection (16% vs 71%; p < 0.001). Conclusion. A high percentage of bone and soft-tissue tumours can be stained by ICG and the tumour staining with ICG was stable. This approach can be used in both benign and malignant tumours, regardless of whether neoadjuvant chemotherapy is adopted. The technique is also useful to detect tumour residuals in the wound, especially in patients undergoing piecemeal resection. Cite this article: Bone Joint J 2023;105-B(5):551–558

Aims. Gram-negative periprosthetic joint infection (PJI) has been poorly studied despite its rapidly increasing incidence. Treatment with one-stage revision using intra-articular (IA) infusion of antibiotics may offer a reasonable alternative with a distinct advantage of providing a means of delivering the drug in high concentrations. Carbapenems are regarded as the last line of defense against severe Gram-negative or polymicrobial infection. This study presents the results of one-stage revision using intra-articular carbapenem infusion for treating Gram-negative PJI, and analyzes the characteristics of bacteria distribution and drug sensitivity. Methods. We retrospectively reviewed 32 patients (22 hips and 11 knees) who underwent single-stage revision combined with IA carbapenem infusion between November 2013 and March 2020. The IA and intravenous (IV) carbapenem infusions were administered for a single Gram-negative infection, and IV vancomycin combined with IA carbapenems and vancomycin was applied for polymicrobial infection including Gram-negative bacteria. The bacterial community distribution, drug sensitivity, infection control rate, functional recovery, and complications were evaluated. Reinfection or death caused by PJI was regarded as a treatment failure. Results. Gram-negative PJI was mainly caused by Escherichia coli (8/34), Enterobacter cloacae (7/34), and Klebsiella pneumoniae (5/34). Seven cases (7/32) involved polymicrobial PJIs. The resistance rates of penicillin, cephalosporin, quinolones, and sulfonamides were > 10%, and all penicillin and partial cephalosporins (first and second generation) were > 30%. Of 32 cases, treatment failed to eradicate infection in only three cases (9.4%), at a mean follow-up of 55.1 months (SD 25 to 90). The mean postoperative Harris Hip Score and Hospital for Special Surgery knee score at the most recent follow-up were 81 (62 to 91) and 79 (56 to 89), respectively. One patient developed a fistula, and another presented with a local rash on an infected joint. Conclusion. The use of IA carbapenem delivered alongside one-stage revision effectively controlled Gram-negative infection and obtained acceptable clinical outcomes with few complications. Notably, first- and second-generation cephalosporins and penicillin should be administrated with caution, due to a high incidence of resistance. Cite this article: Bone Joint J 2023;105-B(3):284–293

Aims. Periprosthetic joint infections (PJIs) with prior multiple failed surgery for reinfection represent a huge challenge for surgeons because of poor vascular supply and biofilm formation. This study aims to determine the results of single-stage revision using intra-articular antibiotic infusion in treating this condition. Methods. A retrospective analysis included 78 PJI patients (29 hips; 49 knees) who had undergone multiple prior surgical interventions. Our cohort was treated with single-stage revision using a supplementary intra-articular antibiotic infusion. Of these 78 patients, 59 had undergone more than two prior failed debridement and implant retentions, 12 patients had a failed arthroplasty resection, three hips had previously undergone failed two-stage revision, and four had a failed one-stage revision before their single-stage revision. Previous failure was defined as infection recurrence requiring surgical intervention. Besides intravenous pathogen-sensitive agents, an intra-articular infusion of vancomycin, imipenem, or voriconazole was performed postoperatively. The antibiotic solution was soaked into the joint for 24 hours for a mean of 16 days (12 to 21), then extracted before next injection. Recurrence of infection and clinical outcomes were evaluated. Results. A total of 68 patients (87.1%) were free of infection at a mean follow-up time of 85 months (24 to 133). The seven-year infection-free survival was 87.6% (95% confidence interval (CI) 79.4 to 95.8). No significant difference in infection-free survival was observed between hip and knee PJIs (91.5% (95% CI 79.9 to 100) vs 84.7% (95% CI 73.1 to 96.3); p = 0.648). The mean postoperative Harris Hip Score was 76.1 points (63.2 to 92.4) and Hospital for Special Surgery score was 78. 2 (63.2 to 92.4) at the most recent assessment. Polymicrobial and fungal infections accounted for 14.1% (11/78) and 9.0% (7/78) of all cases, respectively. Conclusion. Single-stage revision with intra-articular antibiotic infusion can provide high antibiotic concentration in synovial fluid, thereby overcoming reduced vascular supply and biofilm formation. This supplementary route of administration may be a viable option in treating PJI after multiple failed prior surgeries for reinfection. Cite this article: Bone Joint J 2022;104-B(7):867–874

Aims. Trained immunity confers non-specific protection against various types of infectious diseases, including bone and joint infection. Platelets are active participants in the immune response to pathogens and foreign substances, but their role in trained immunity remains elusive. Methods. We first trained the innate immune system of C57BL/6 mice via intravenous injection of two toll-like receptor agonists (zymosan and lipopolysaccharide). Two, four, and eight weeks later, we isolated platelets from immunity-trained and control mice, and then assessed whether immunity training altered platelet releasate. To better understand the role of immunity-trained platelets in bone and joint infection development, we transfused platelets from immunity-trained mice into naïve mice, and then challenged the recipient mice with Staphylococcus aureus or Escherichia coli. Results. After immunity training, the levels of pro-inflammatory cytokines (tumour necrosis factor alpha (TNF-α), interleukin (IL)-17A) and chemokines (CCL5, CXCL4, CXCL5, CXCL7, CXCL12) increased significantly in platelet releasate, while the levels of anti-inflammatory cytokines (IL-4, IL-13) decreased. Other platelet-secreted factors (e.g. platelet-derived growth factor (PDGF)-AA, PDGF-AB, PDGF-BB, cathepsin D, serotonin, and histamine) were statistically indistinguishable between the two groups. Transfusion of platelets from trained mice into naïve mice reduced infection risk and bacterial burden after local or systemic challenge with either S. aureus or E. coli. Conclusion. Immunity training altered platelet releasate by increasing the levels of inflammatory cytokines/chemokines and decreasing the levels of anti-inflammatory cytokines. Transfusion of platelets from immunity-trained mice conferred protection against bone and joint infection, suggesting that alteration of platelet releasate might be an important mechanism underlying trained immunity and may have clinical implications. Cite this article: Bone Joint Res 2022;11(2):73–81

Aims. In the absence of an identified organism, single-stage revision is contraindicated in prosthetic joint infection (PJI). However, no studies have examined the use of intra-articular antibiotics in combination with single-stage revision in these cases. In this study, we present the results of single-stage revision using intra-articular antibiotic infusion for treating culture-negative (CN) PJI. Methods. A retrospective analysis between 2009 and 2016 included 51 patients with CN PJI who underwent single-stage revision using intra-articular antibiotic infusion; these were compared with 192 culture-positive (CP) patients. CN patients were treated according to a protocol including intravenous vancomycin and a direct intra-articular infusion of imipenem and vancomycin alternately used in the morning and afternoon. In the CP patients, pathogen-sensitive intravenous (IV) antibiotics were administered for a mean of 16 days (12 to 21), and for resistant cases, additional intra-articular antibiotics were used. The infection healing rate, Harris Hip Score (HHS), and Hospital for Special Surgery (HSS) knee score were compared between CN and CP groups. Results. Of 51 CN patients, 46 (90.2%) required no additional medical treatment for recurrent infection at a mean of 53.2 months (24 to 72) of follow-up. Impaired kidney function occurred in two patients, and one patient had a local skin rash. No significant difference in the infection control rate was observed between CN and CP PJIs (90.2% (46/51) versus 94.3% (181/192); p = 0.297). The HHS of the CN group showed no substantial difference from that of CP cases (79 versus 81; p = 0.359). However, the CN group showed a mean HSS inferior to that of the CP group (76 versus 80; p = 0.027). Conclusion. Single-stage revision with direct intra-articular antibiotic infusion can be effective in treating CN PJI, and can achieve an infection control rate similar to that in CP patients. However, in view of systemic toxicity, local adverse reactions, and higher costs, additional strong evidence is needed to verify these treatment regimens. Cite this article: Bone Joint J 2020;102-B(3):336–344

Aims. Antibiotic prophylaxis involving timely administration of appropriately dosed antibiotic is considered effective to reduce the risk of surgical site infection (SSI) after total hip and total knee arthroplasty (THA/TKA). Cephalosporins provide effective prophylaxis, although evidence regarding the optimal timing and dosage of prophylactic antibiotics is inconclusive. The aim of this study is to examine the association between cephalosporin prophylaxis dose, timing, and duration, and the risk of SSI after THA/TKA. Methods. A prospective multicentre cohort study was undertaken in consenting adults with osteoarthritis undergoing elective primary TKA/THA at one of 19 high-volume Australian public/private hospitals. Data were collected prior to and for one-year post surgery. Logistic regression was undertaken to explore associations between dose, timing, and duration of cephalosporin prophylaxis and SSI. Data were analyzed for 1,838 participants. There were 264 SSI comprising 63 deep SSI (defined as requiring intravenous antibiotics, readmission, or reoperation) and 161 superficial SSI (defined as requiring oral antibiotics) experienced by 249 (13.6%) participants within 365 days of surgery. Results. In adjusted modelling, factors associated with a significant reduction in any SSI and deep SSI included: correct weight-adjusted dose (any SSI; adjusted odds ratio (aOR) 0.68 (95% confidence interval (CI) 0.47 to 0.99); p = 0.045); commencing preoperative cephalosporin within 60 minutes (any SSI, aOR 0.56 (95% CI 0.36 to 0.89); p = 0.012; deep SSI, aOR 0.29 (95% CI 0.15 to 0.59); p < 0.001) or 60 minutes or longer prior to skin incision (aOR 0.35 (95% CI 0.17 to 0.70); p = 0.004; deep SSI, AOR 0.27 (95% CI 0.09 to 0.83); p = 0.022), compared to at or after skin incision. Other factors significantly associated with an increased risk of any SSI, but not deep SSI alone, were receiving a non-cephalosporin antibiotic preoperatively (aOR 1.35 (95% CI 1.01 to 1.81); p = 0.044) and changing cephalosporin dose (aOR 1.76 (95% CI 1.22 to 2.57); p = 0.002). There was no difference in risk of any or deep SSI between the duration of prophylaxis less than or in excess of 24 hours. Conclusion. Ensuring adequate, weight-adjusted dosing and early, preoperative delivery of prophylactic antibiotics may reduce the risk of SSI in THA/TKA, whereas the duration of prophylaxis beyond 24 hours is unnecessary. Cite this article: Bone Jt Open 2022;3(3):252–260

Aims. Intra-articular administration of antibiotics during primary total knee arthroplasty (TKA) may represent a safe, cost-effective strategy to reduce the risk of acute periprosthetic joint infection (PJI). Vancomycin with an aminoglycoside provides antimicrobial cover for most organisms isolated from acute PJI after TKA. However, the intra-articular doses required to achieve sustained therapeutic intra-articular levels while remaining below toxic serum levels is unknown. The purpose of this study is to determine the intra-articular and serum levels of vancomycin and tobramycin over the first 24 hours postoperatively after intra-articular administration in primary cementless TKA. Methods. A prospective cohort study was performed. Patients were excluded if they had poor renal function, known allergic reaction to vancomycin or tobramycin, received intravenous vancomycin, or were scheduled for same-day discharge. All patients received 600 mg tobramycin and 1 g of vancomycin powder suspended in 25 cc of normal saline and injected into the joint after closure of the arthrotomy. Serum from peripheral venous blood and drain fluid samples were collected at one, four, and 24 hours postoperatively. All concentrations are reported in µg per ml. Results. A total of 22 patients were included in final analysis. At one, four, and 24 hours postoperatively, mean (95% confidence interval (CI)) serum concentrations were 2.4 (0.7 to 4.1), 5.0 (3.1 to 6.9), and 4.8 (2.8 to 6.9) for vancomycin and 4.9 (3.4 to 6.3), 7.0 (5.8 to 8.2), and 1.3 (0.8 to 1.8) for tobramycin; intra-articular concentrations were 1,900.6 (1,492.5 to 2,308.8), 717.9 (485.5 to 950.3), and 162.2 (20.5 to 304.0) for vancomycin and 2,105.3 (1,389.9 to 2,820.6), 403.2 (266.6 to 539.7), and 98.8 (0 to 206.5) for tobramycin. Conclusion. Intra-articular administration of 1 g of vancomycin and 600 mg of tobramycin as a solution after closure of the arthrotomy in primary cementless TKA achieves therapeutic intra-articular concentrations over the first 24 hours postoperatively and does not reach sustained toxic levels in peripheral blood. Cite this article: Bone Joint J 2021;103-B(11):1702–1708

Objectives. Meropenem may be an important drug in the treatment of open tibial fractures and chronic osteomyelitis. Therefore, the objective of this study was to describe meropenem pharmacokinetics in plasma, subcutaneous adipose tissue (SCT), and cancellous bone using microdialysis in a porcine model. Methods. Six female pigs were assigned to receive 1000 mg of meropenem intravenously over five minutes. Measurements of meropenem were obtained from plasma, SCT, and cancellous bone for eight hours thereafter. Microdialysis was applied for sampling in solid tissues. The meropenem concentrations were determined using ultra-high-performance liquid chromatography. Results. The penetration of meropenem into cancellous bone, expressed as the ratio of plasma to cancellous bone area under the concentration-curve from zero to the last measured value, was incomplete and delayed. The time with concentration above the minimal inhibitory concentration (T. >MIC. ), for an MIC of 0.5 μg/ml, was shorter for cancellous bone in comparison with both plasma and SCT. For MICs above 0.5 μg/ml, T. >MIC. in cancellous bone was only shorter than SCT. Considering an MIC of 4 μg/ml, no animals achieved the target of 40% T. >MIC. in plasma and cancellous bone, while less than 20% achieved it in SCT. Conclusion. The main finding of this study was short T. >MIC. in cancellous bone after intravenous administration of 1000 mg meropenem. Consequently, in order to achieve sufficient tissue concentration in the cases of open tibial fractures and chronic osteomyelitis, supplemental application of meropenem may be necessary. Cite this article: P. Hanberg, A. Lund, K. Søballe, M. Bue. Single-dose pharmacokinetics of meropenem in porcine cancellous bone determined by microdialysis: An animal study. Bone Joint Res 2019;8:342–348. DOI: 10.1302/2046-3758.87.BJR-2018-0308.R1

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

Aims. Manipulation under anaesthesia (MUA) remains an effective intervention to address restricted range of motion (ROM) after total knee arthroplasty (TKA) and occurs in 2% to 3% of primary TKAs at our institution. Since there are few data on the outcomes of MUA with different anaesthetic methods, we sought to compare the outcomes of patients undergoing MUA with intravenous (IV) sedation and neuraxial anaesthesia. Methods. We identified 548 MUAs after primary TKA (136 IV sedation, 412 neuraxial anaesthesia plus IV sedation) from March 2016 to July 2019. The mean age of this cohort was 62 years (35 to 88) with a mean body mass index of 31 kg/m. 2. (18 to 49). The mean time from primary TKA to MUA was 10.2 weeks (6.2 to 24.3). Pre-MUA ROM was similar between groups; overall mean pre-MUA extension was 4.2° (p = 0.452) and mean pre-MUA flexion was 77° (p = 0.372). We compared orthopaedic complications, visual analogue scale (VAS) pain scores, length of stay (LOS), and immediate and three-month follow-up knee ROM between these groups. Results. Following MUA, patients with IV sedation had higher mean VAS pain scores of 5.2 (SD 1.8) compared to 4.1 (SD = 1.5) in the neuraxial group (p < 0.001). The mean LOS was shorter in patients that received IV sedation (9.5 hours (4 to 31)) compared to neuraxial anaesthesia (11.9 hours (4 to 51)) (p = 0.009), but an unexpected overnight stay was similar in each group (8.6%). Immediate-post MUA ROM was 1° to 121° in the IV sedation group and 0.9° to 123° in the neuraxial group (p = 0.313). Three-month follow-up ROM was 2° to 108° in the IV sedation group and 1.9° to 110° in the neuraxial anaesthesia group (p = 0.325) with a mean loss of 13° (ranging from 5° gain to 60° loss), in both groups by three months. No patients in either group sustained a complication. Conclusion. IV sedation alone and neuraxial anaesthesia are both effective anaesthetic methods for MUA after primary TKA. Surgeons and anaesthetists should offer these anaesthetic techniques to match patient-specific needs as the orthopaedic outcomes are similar. Also, patients should be counselled that ROM following MUA may decrease over time. Cite this article: Bone Joint J 2021;103-B(6 Supple A):126–130