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

Aims. Knee osteoarthritis (OA) is characterized by a chronic inflammatory process involving multiple cytokine pathways, leading to articular cartilage degeneration. Intra-articular therapies using pharmaceutical or autologous anti-inflammatory factors offer potential non-surgical treatment options. Autologous protein solution (APS) is one such product that uses the patient’s blood to produce a concentrate of cells and anti-inflammatory cytokines. This study evaluated the effect of a specific APS intra-articular injection (nSTRIDE) on patient-reported outcome measures compared to saline in moderate knee OA. Methods. A parallel, double-blinded, placebo-controlled randomized controlled trial was conducted, where patients with unilateral moderate knee OA (Kellgren-Lawrence grade 2 or 3) received either nSTRIDE or saline (placebo) injection to their symptomatic knee. The primary outcome was the difference in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score at 12 months post-intervention. Secondary outcomes included WOMAC component scores, Knee injury and Osteoarthritis Outcome Score (KOOS), and visual analogue scale (VAS) scores at all follow-up timepoints (three, six, and 12 months). Results. A total of 40 patients were analyzed (21 nSTRIDE; 19 saline) in the study. No significant difference was found between nSTRIDE and saline groups for WOMAC total score at 12 months (mean difference -10.4 (95% CI -24.4 to 3.6; p = 0.141). There were no significant differences in WOMAC or KOOS scores across all timepoints. VAS scores favoured the saline group for both rest and worst pain scales at 12 months post-injection (mean difference (worst) 12 months 21.5 (95% CI 6.2 to 36.8; p = 0.008); mean difference (rest) 12 months 17.8 (95% CI 2.2 to 33.4; p = 0.026)). There were no adverse events recorded in either study group. Conclusion. Our study demonstrates no significant differences between nSTRIDE and saline groups in KOOS and WOMAC scores over time. Notably, APS injection resulted in significantly worse pain symptoms at 12 months compared to saline injection. Cite this article: Bone Joint J 2024;106-B(9):907–915

Aims. Stiffness is a common complication after total knee arthroplasty (TKA). Pathogenesis is not understood, treatment options are limited, and diagnosis is challenging. The aim of this study was to investigate if MRI can be used to visualize intra-articular scarring in patients with stiff, painful knee arthroplasties. Methods. Well-functioning primary TKAs (n = 11), failed non-fibrotic TKAs (n = 5), and patients with a clinical diagnosis of fibrosis. 1. (n = 8) underwent an MRI scan with advanced metal suppression (Slice Encoding for Metal Artefact Correction, SEMAC) with gadolinium contrast. Fibrotic tissue (low intensity on T1 and T2, low-moderate post-contrast enhancement) was quantified (presence and tissue thickness) in six compartments: supra/infrapatella, medial/lateral gutters, and posterior medial/lateral. Results. Fibrotic tissue was identified in all patients studied. However, tissue was significantly thicker in fibrotic patients (4.4 mm ± 0.2 mm) versus non-fibrotic (2.5 mm ± 0.4 mm) and normal TKAs (1.9 mm ± 0.2 mm, p = < 0.05). Significant (> 4 mm thick) tissue was seen in 26/48 (54%) of compartments examined in the fibrotic group, compared with 17/30 (57%) non-fibrotic, and 10/66 (15%) normal TKAs. Although revision surgery did improve range of movement (ROM) in all fibrotic patients, clinically significant restriction remained post-surgery. Conclusion. Stiff TKAs contain intra-articular fibrotic tissue that is identifiable by MRI. Studies should evaluate whether MRI is useful for surgical planning of debridement, and as a non-invasive measurement tool following interventions for stiffness caused by fibrosis. Revision for stiffness can improve ROM, but outcomes are sub-optimal and new treatments are required. Cite this article: Bone Joint J 2020;102-B(10):1331–1340

Aims. Single-shot adductor canal block (ACB) after total knee arthroplasty (TKA) for postoperative analgesia is a common modality. Patients can experience breakthrough pain when the effect of ACB wears off. Local anaesthetic infusion through an intra-articular catheter (IAC) can help manage breakthrough pain after TKA. We hypothesized that combined ACB with ropivacaine infusion through IAC is associated with better pain relief compared to ACB used alone. Methods. This study was a prospective double-blinded placebo-controlled randomized controlled trial to compare the efficacy of combined ACB+ IAC-ropivacaine infusion (study group, n = 68) versus single-shot ACB+ intra-articular normal saline placebo (control group, n = 66) after primary TKA. The primary outcome was assessment of pain, using the visual analogue scale (VAS) recorded at 6, 12, 24, and 48 hours after surgery. Secondary outcomes included active knee ROM 48 hours after surgery and additional requirement of analgesia for breakthrough pain. Results. The study group (mean visual analogue scale (VAS) pain score of 5.5 (SD 0.889)) experienced significant reduction in pain 12 hours after surgery compared to the control group (mean VAS 6.62 (SD 1.356); mean difference = 1.12, 95% confidence interval (CI) -1.46 to 0.67; p < 0.001), and pain scores on postoperative day (POD) 1 and POD-2 were lower in the study group compared to the control group (mean difference in VAS pain = 1.04 (-1.39 to -0.68, 95% CI, p < 0.001). Fewer patients in the study group (0 vs 3 in the control group) required additional analgesia for breakthrough pain, but this was not statistically significant. The study group had significantly increased active knee flexion (mean flexion 86.4° (SD 7.22°)), compared to the control group (mean 73.86° (SD 7.88°), mean difference = 12.54, 95% CI 9.97 to 15.1; p < 0.014). Conclusion. Combined ACB+ ropivacaine infusion via IAC is a safe, reproducible analgesic modality after primary TKA, with superior analgesia compared to ACB alone. Further large volume trials are warranted to generate evidence on clinical significance on analgesia after TKA. Cite this article: Bone Jt Open 2021;2(12):1082–1088

Aims. Outcomes of current operative treatments for arthrofibrosis after total knee arthroplasty (TKA) are not consistently positive or predictable. Pharmacological in vivo studies have focused mostly on prevention of arthrofibrosis. This study used a rabbit model to evaluate intra-articular (IA) effects of celecoxib in treating contracted knees alone, or in combination with capsular release. Methods. A total of 24 rabbits underwent contracture-forming surgery with knee immobilization followed by remobilization surgery at eight weeks. At remobilization, one cohort underwent capsular release (n = 12), while the other cohort did not (n = 12). Both groups were divided into two subcohorts (n = 6 each) – one receiving IA injections of celecoxib, and the other receiving injections of vehicle solution (injections every day for two weeks after remobilization). Passive extension angle (PEA) was assessed in live rabbits at 10, 16, and 24 weeks, and disarticulated limbs were analyzed for capsular stiffness at 24 weeks. Results. IA celecoxib resulted in greater mean PEA at ten weeks (69.6° (SD 4.6) vs 45.2° (SD 9.6), p = 0.004), 16 weeks (109.8° (SD 24.2) vs 60.9° (SD10.9), p = 0.004), and 24 weeks (101.0° (SD 8.0) vs 66.3° (SD 5.8), p = 0.004). Capsular stiffness was significantly reduced with IA celecoxib (2.72 Newton per cm (N·cm)/° (SD 1.04), p = 0.008), capsular release (2.41 N·cm/° (SD 0.80), p = 0.008), and capsular release combined with IA celecoxib (3.56 N·cm/° (SD 0.99), p = 0.018) relative to IA vehicle (6.09 N·cm/° (SD 1.64)). Conclusion. IA injections of a celecoxib led to significant improvements in passive extension angles, with reduced capsular stiffness, when administered to rabbit knees with established experimental contracture. Celecoxib was superior to surgical release, and the combination of celecoxib and a surgical release did not provide any additional value. Cite this article: Bone Joint Res 2022;11(1):32–39

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

Aims. Recent studies have suggested that corticosteroid injections into the knee may harm the joint resulting in cartilage loss and possibly accelerating the progression of osteoarthritis (OA). The aim of this study was to assess whether patients with, or at risk of developing, symptomatic osteoarthritis of the knee who receive intra-articular corticosteroid injections have an increased risk of requiring arthroplasty. Methods. We used data from the Osteoarthritis Initiative (OAI), a multicentre observational cohort study that followed 4,796 patients with, or at risk of developing, osteoarthritis of the knee on an annual basis with follow-up available up to nine years. Increased risk for symptomatic OA was defined as frequent knee symptoms (pain, aching, or stiffness) without radiological evidence of OA and two or more risk factors, while OA was defined by the presence of both femoral osteophytes and frequent symptoms in one or both knees. Missing data were imputed with multiple imputations using chained equations. Time-dependent propensity score matching was performed to match patients at the time of receving their first injection with controls. The effect of corticosteroid injections on the rate of subsequent (total and partial) knee arthroplasty was estimated using Cox proportional-hazards survival analyses. Results. After removing patients lost to follow-up, 3,822 patients remained in the study. A total of 249 (31.3%) of the 796 patients who received corticosteroid injections, and 152 (5.0%) of the 3,026 who did not, had knee arthroplasty. In the matched cohort, Cox proportional-hazards regression resulted in a hazard ratio of 1.57 (95% confidence interval (CI) 1.37 to 1.81; p < 0.001) and each injection increased the absolute risk of arthroplasty by 9.4% at nine years’ follow-up compared with those who did not receive injections. Conclusion. Corticosteroid injections seem to be associated with an increased risk of knee arthroplasty in patients with, or at risk of developing, symptomatic OA of the knee. These findings suggest that a conservative approach regarding the treatment of these patients with corticosteroid injections should be recommended. Cite this article: Bone Joint J 2020;102-B(5):586–592

Intra-articular resection of bone with soft-tissue balancing and total knee replacement (TKR) has been described for the treatment of patients with severe osteoarthritis of the knee associated with an ipsilateral malunited femoral fracture. However, the extent to which deformity in the sagittal plane can be corrected has not been addressed. We treated 12 patients with severe arthritis of the knee and an extra-articular malunion of the femur by TKR with intra-articular resection of bone and soft-tissue balancing. The femora had a mean varus deformity of 16° (8° to 23°) in the coronal plane. There were seven recurvatum deformities with a mean angulation of 11° (6° to 15°) and five antecurvatum deformities with a mean angulation of 12° (6° to 15°). The mean follow-up was 93 months (30 to 155). The median Knee Society knee and function scores improved from 18.7 (0 to 49) and 24.5 (10 to 50) points pre-operatively to 93 (83 to 100) and 90 (70 to 100) points at the time of the last follow-up, respectively. The mean mechanical axis of the knee improved from 22.6° of varus (15° to 27° pre-operatively to 1.5° of varus (3° of varus to 2° of valgus) at the last follow-up. The recurvatum deformities improved from a mean of 11° (6° to 15°) pre-operatively to 3° (0° to 6°) at the last follow-up. The antecurvatum deformities in the sagittal plane improved from a mean of 12° (6° to 16°) pre-operatively to 4.4° (0° to 8°) at the last follow-up. Apart from varus deformities, TKR with intra-articular bone resection effectively corrected the extra-articular deformity of the femur in the presence of antecurvatum of up to 16° and recurvatum of up to 15°

We reviewed 231 patients who had undergone total knee replacement with an AGC (Biomet) implant over a period of 2.5 years. After applying exclusion criteria and with some loss to follow-up, there were 144 patients available for study. These were divided into two groups; those who had received intra-articular steroid in the 11 months before surgery and those who had not. There were three deep infections, all of which occurred in patients who had received a steroid injection. The incidence of superficial infection was not significantly different in the two groups. Five patients had undergone investigation for suspected deep infection because of persistent swelling or pain and all of these had received an intra-articular injection pre-operatively. We conclude that the decision to administer intra-articular steroids to a patient who may be a candidate for total knee replacement should not be taken lightly because of a risk of post-operative deep infection

Objectives. The goal of this study was to determine whether intra-articular administration of the potentially anti-fibrotic agent decorin influences the expression of genes involved in the fibrotic cascade, and ultimately leads to less contracture, in an animal model. Methods. A total of 18 rabbits underwent an operation on their right knees to form contractures. Six limbs in group 1 received four intra-articular injections of decorin; six limbs in group 2 received four intra-articular injections of bovine serum albumin (BSA) over eight days; six limbs in group 3 received no injections. The contracted limbs of rabbits in group 1 were biomechanically and genetically compared with the contracted limbs of rabbits in groups 2 and 3, with the use of a calibrated joint measuring device and custom microarray, respectively. Results. There was no statistical difference in the flexion contracture angles between those limbs that received intra-articular decorin versus those that received intra-articular BSA (66° vs 69°; p = 0.41). Likewise, there was no statistical difference between those limbs that received intra-articular decorin versus those who had no injection (66° vs 72°; p = 0.27). When compared with BSA, decorin led to a statistically significant increase in the mRNA expression of 12 genes (p < 0.01). In addition, there was a statistical change in the mRNA expression of three genes, when compared with those without injection. . Conclusions. In this model, when administered intra-articularly at eight weeks, 2 mg of decorin had no significant effect on joint contractures. However, our genetic analysis revealed a significant alteration in several fibrotic genes. Cite this article: Bone Joint Res 2014;3:82–8

The administration of intra-articular local anaesthetic is common following arthroscopy of the knee. However, recent evidence has suggested that bupivacaine may be harmful to articular cartilage. This study aimed to establish whether infiltration of bupivacaine around the portals is as effective as intra-articular injection. We randomised 137 patients to receive either 20 ml 0.5% bupivacaine introduced into the joint (group 1) or 20 ml 0.5% bupivacaine infiltrated only around the portals (group 2) following arthroscopy. A visual analogue scale was administered one hour post-operatively to assess pain relief. Both patients and observers were blinded to the treatment group. A power calculation was performed. The mean visual analogue score was 3.24 (. sd. 2.20) in group I and 3.04 (. sd. 2.31) in group 2. This difference was not statistically significant (p = 0.62). Infiltration of bupivacaine around the portals had an equivalent effect on pain scores at one hour, and we would therefore recommend this technique to avoid the possible chondrotoxic effect of intra-articular bupivacaine

Aims. To present our experience of using a combination of intra-articular osteotomy and external fixation to treat different deformities of the knee. Patients and Methods. A total of six patients with a mean age of 26.5 years (15 to 50) with an abnormal hemi-joint line convergence angle (HJLCA) and mechanical axis deviation (MAD) were included. Elevation of a tibial hemiplateau or femoral condylar advancement was performed and limb lengthening with correction of residual deformity using a circular or monolateral Ilizarov frame. Results. At a mean follow-up of 2.8 years (1.5 to 4.1), the mean HJLCA improved from 15.6° (10° to 23°) pre-operatively to 0.4° (0° to 2°). The mean MAD improved from 70.0 mm (20.1 to 118.5) pre-operatively to 9.1 mm (3 to 15). The mean tibiofemoral angle improved from 31.0° (8° to 54°) pre-operatively to 4.9° (2° to 8°). The mean limb-length discrepancy decreased from 6.3 cm (2.9 to 13.6) pre-operatively to 1.1 cm (0 to 5). All osteotomies and distraction zones healed without complications. Conclusion. The use of intra-articular corrective osteotomies combined with the Ilizarov technique allowed correction of deformities of the knee joint with satisfactory HJLCA and overall mechanical axis in six patients with a good functional and cosmetic outcome in the short term. Cite this article: Bone Joint J 2017;99-B:204–10

Objective . Dunkin Hartley guinea pigs, a commonly used animal model of osteoarthritis, were used to determine if high frequency ultrasound can ensure intra-articular injections are accurately positioned in the knee joint. Methods. A high-resolution small animal ultrasound system with a 40 MHz transducer was used for image-guided injections. A total of 36 guinea pigs were anaesthetised with isoflurane and placed on a heated stage. Sterile needles were inserted directly into the knee joint medially, while the transducer was placed on the lateral surface, allowing the femur, tibia and fat pad to be visualised in the images. B-mode cine loops were acquired during 100 µl. We assessed our ability to visualise 1) important anatomical landmarks, 2) the needle and 3) anatomical changes due to the injection. . Results. From the ultrasound images, we were able to visualise clearly the movement of anatomical landmarks in 75% of the injections. The majority of these showed separation of the fat pad (67.1%), suggesting the injections were correctly delivered in the joint space. We also observed dorsal joint expansion (23%) and patellar tendon movement (10%) in a smaller subset of injections. Conclusion. The results demonstrate that this image-guided technique can be used to visualise the location of an intra-articular injection in the joints of guinea pigs. Future studies using an ultrasound-guided approach could help improve the injection accuracy in a variety of anatomical locations and animal models, in the hope of developing anti-arthritic therapies. Cite this article: Bone Joint Res 2015;4:1–5

We carried out a prospective study in order to establish to what extent the intra-articular evaluation undertaken during arthroscopy of the knee differed between surgeons. Two senior specialist registrars and a consultant orthopaedic surgeon with a special interest in knee surgery were involved. A total of 78 knee arthroscopies (78 patients) was studied. Arthroscopy was first carried out by the trainee and then by the senior author (ACWH). The intra-articular evaluation during the arthroscopy was recorded independently by a third person in the operating theatre. Data were collected to record variations in examination under anaesthesia, the morphology and pathology of the menisci and anterior cruciate ligament and the state of the articular surfaces. The overall interobserver variation was 20% in all categories. We question the published results of intra-articular evaluation during knee arthroscopy when surgeons of different levels of experience are involved in a single study

The postoperative analgesic effects of intra-articular injections of bupivacaine and/or morphine were examined prospectively in 437 patients who had total knee replacement for osteoarthritis. They were divided randomly into four groups. Group I received 10 mg of morphine (1 ml) and 9 ml of saline, group II received 10 ml of bupivacaine (2.5 mg/ml), group III received 10 ml of saline, and group IV received 10 mg of morphine (1 ml) and 9 ml of bupivacaine (2.5 mg/ml). All analgesics administered in the first 24 hours after operation were recorded. The patients rated their pain on the McGill-Melzack scale at 1, 6, 12 and 24 hours. No significant differences were found between any of the groups in the use of Demoral and/or Toradol in 24 hours, the length of stay in hospital or the pain rating at 1, 6, 12 or 24 hours. Patients in groups I and IV, whose injections included morphine, used significantly more morphine in the first 24 postoperative hours than did groups II or III

Aim

Mesenchymal stem cells (MSCs) have several properties that may support their use as an early treatment option for osteoarthritis (OA). This study investigated the role of multiple injections of allogeneic bone marrow-derived stem cells (BMSCs) to alleviate the progression of osteoarthritic changes in the various structures of the mature rabbit knee in an anterior cruciate ligament (ACL)-deficient OA model.

Aims. As has been shown in larger animal models, knee immobilization can lead to arthrofibrotic phenotypes. Our study included 168 C57BL/6J female mice, with 24 serving as controls, and 144 undergoing a knee procedure to induce a contracture without osteoarthritis (OA). Methods. Experimental knees were immobilized for either four weeks (72 mice) or eight weeks (72 mice), followed by a remobilization period of zero weeks (24 mice), two weeks (24 mice), or four weeks (24 mice) after suture removal. Half of the experimental knees also received an intra-articular injury. Biomechanical data were collected to measure passive extension angle (PEA). Histological data measuring area and thickness of posterior and anterior knee capsules were collected from knee sections. Results. Experimental knees immobilized for four weeks demonstrated mean PEAs of 141°, 72°, and 79° after zero, two, and four weeks of remobilization (n = 6 per group), respectively. Experimental knees demonstrated reduced PEAs after two weeks (p < 0.001) and four weeks (p < 0.0001) of remobilization compared to controls. Following eight weeks of immobilization, experimental knees exhibited mean PEAs of 82°, 73°, and 72° after zero, two, and four weeks of remobilization, respectively. Histological analysis demonstrated no cartilage degeneration. Similar trends in biomechanical and histological properties were observed when intra-articular violation was introduced. Conclusion. This study established a novel mouse model of robust knee contracture without evidence of OA. This was appreciated consistently after eight weeks of immobilization and was irrespective of length of remobilization. As such, this arthrofibrotic model provides opportunities to investigate molecular pathways and therapeutic strategies. Cite this article: Bone Joint Res 2023;12(1):58–71

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 if the local delivery of vancomycin and tobramycin in primary total knee arthroplasty (TKA) can achieve intra-articular concentrations exceeding the minimum inhibitory concentration thresholds for bacteria causing acute prosthetic joint infection (PJI). Methods. Using a retrospective single-institution database of all primary TKAs performed between January 1 2014 and May 7 2019, we identified patients with acute PJI that were managed surgically within 90 days of the initial procedure. The organisms from positive cultures obtained at the time of revision were tested for susceptibility to gentamicin, tobramycin, and vancomycin. A prospective study was then performed to determine the intra-articular antibiotic concentration on postoperative day one after primary TKA using one of five local antibiotic delivery strategies with tobramycin and/or vancomycin mixed into the polymethylmethacrylate (PMMA) or vancomycin powder. Results. A total of 19 patients with acute PJI after TKA were identified and 29 unique bacterial isolates were recovered. The mean time to revision was 37 days (6 to 84). Nine isolates (31%) were resistant to gentamicin, ten (34%) were resistant to tobramycin, and seven (24%) were resistant to vancomycin. Excluding one Fusobacterium nucleatum, which was resistant to all three antibiotics, all isolates resistant to tobramycin or gentamicin were susceptible to vancomycin and vice versa. Overall, 2.4 g of tobramycin hand-mixed into 80 g of PMMA and 1 g of intra-articular vancomycin powder consistently achieved concentrations above the minimum inhibitory concentrations of susceptible organisms. Conclusion. One-third of bacteria causing acute PJI after primary TKA were resistant to the aminoglycosides commonly mixed into PMMA, and one-quarter were resistant to vancomycin. With one exception, all bacteria resistant to tobramycin were susceptible to vancomycin and vice versa. Based on these results, the optimal cover for organisms causing most cases of acute PJI after TKA can be achieved with a combination of tobramycin mixed in antibiotic cement, and vancomycin powder. Cite this article: Bone Joint J 2020;102-B(6 Supple A):163–169

Aims. Platelet-rich plasma (PRP) intra-articular injections may provide a simple and minimally invasive treatment for early-stage knee osteoarthritis (OA). This has led to an increase in its adoption as a treatment for knee OA, although there is uncertainty about its efficacy and benefit. We hypothesized that patients with early-stage symptomatic knee OA who receive multiple PRP injections will have better clinical outcomes than those receiving single PRP or placebo injections. Methods. A double-blinded, randomized placebo-controlled trial was performed with three groups receiving either placebo injections (Normal Saline), one PRP injection followed by two placebo injections, or three PRP injections. Each injection was given one week apart. Outcomes were prospectively collected prior to intervention and then at six weeks, three months, six months, and 12 months post-intervention. Primary outcome measures were Knee Injury and Osteoarthritis Outcome Score (KOOS) and EuroQol five-dimension five-level index (EQ-5D-5L). Secondary outcomes included visual analogue scale for pain and patient subjective assessment of the injections. Results. A total of 102 patients were recruited. The follow-up period was 12 months, at intervals of six weeks, 12 weeks, six months, and 12 months. KOOS-Total significantly improved in all groups at these time intervals compared to pre-injection. There was an improvement in EQ-5D-5L index scores in saline and single injection groups, but not in the multiple injection group. Comparison of treatment groups showed no additional beneficial effect of single or multiple PRP injections above that displayed in the saline injection group. Subjective patient satisfaction and recommendation of treatment received demonstrated a similar pattern in all the groups. There was no indication of superiority of either single or multiple PRP injections compared to saline injections. Conclusion. There is no evidence that single or multiple PRP had any additional beneficial effect compared to saline injection up to 12 months, follow-up after treatment of early stage symptomatic OA of the knee. Cite this article: Bone Joint J 2022;104-B(6):663–671