Evaluation of bacteriophage as an adjunct therapy for treatment of peri-prosthetic joint infection caused by Staphylococcus aureus.

Phage therapy offers a potential alternate strategy for the treatment of peri-prosthetic joint infection (PJI), particularly where limited effective antibiotics are available. We undertook preclinical trials to investigate the therapeutic efficacy of a phage cocktail, alone and in combination with vancomycin, to reduce bacterial numbers within the infected joint using a clinically-relevant model of Staphylococcus aureus-induced PJI. Infected animals were randomised to 4 treatment groups, with treatment commencing 21-days post-surgery: bacteriophage alone, vancomycin alone, bacteriophage and vancomycin, and sham. At day 28 post-surgery, animals were euthanised for microbiological and immunological assessment of implanted joints. Treatment with phage alone or vancomycin alone, led to 5-fold and 6.2-fold reductions, respectively in bacterial load within peri-implant tissue compared to sham-treated animals. Compared to sham-treated animals, a 22.5-fold reduction in S. aureus burden was observed within joint tissue of animals that were administered phage in combination with vancomycin, corresponding with decreased swelling in the implanted knee. Microbiological data were supported by evidence of decreased inflammation within the joints of animals administered phage in combination with vancomycin, compared to sham-treated animals. Our findings provide further support for phage therapy as a tolerable and effective adjunct treatment for PJI.

Absence of cytotoxic and inflammatory effects following in vitro exposure of chondrogenically-differentiated human mesenchymal stem cells to adenosine, lidocaine and Mg2+ solution.

BACKGROUND: ALM solution, a combination of adenosine, lidocaine and Mg2+, is an emerging small volume therapy that has been shown to prevent and correct coagulopathy and surgery-related inflammation in preclinical models, though its application in orthopaedic surgery is yet to be demonstrated. The effect of ALM solution on chondrocytes is unknown. The aim of this preliminary study was to investigate the effect of ALM solution on viability and inflammatory responses of chondrogenically-differentiated human bone marrow-derived mesenchymal stem cells (chondro-MSC), in vitro. METHODS: Chondro-MSC were exposed to media only, saline (0.9% NaCl or 1.3% NaCl) only, or saline containing ALM (1 mM adenosine, 3 mM lidocaine, 2.5 mM Mg2+) or tranexamic acid (TXA, 100 mg/ml) for 1 or 4 h. Responses to ALM solutions containing higher lidocaine concentrations were also compared. Chondrocyte viability was determined using WST-8 colorimetric assays and inflammatory cytokine (TNF-α, IL-1ß, IL-8) and matrix metalloproteinases (MMP-3, MMP-12, MMP-13) concentrations using multiplex bead arrays. RESULTS: The viability of chondro-MSC was significantly greater after 1 h treatment with ALM compared to saline (96.2 ± 7.9 versus 75.6 ± 7.3%). Extension of exposure times to 4 h had no significant adverse effect on cell viability after treatment with ALM (1 h, 85.4 ± 5.6 v 4 h, 74.0 ± 15.2%). Cytotoxicity was evident following exposure to solutions containing lidocaine concentrations greater than 30 mM. There were no significant differences in viability (80 ± 5.4 v 57.3 ± 16.2%) or secretion of IL-8 (60 ± 20 v 160 ± 50 pg/ml), MMP-3 (0.95 ± 0.6 v 3.4 ± 1.6 ng/ml), and MMP-13 (4.2 ± 2.4 v 9.2 ± 4.3 ng/ml) in chondro-MSC exposed to saline, ALM or TXA. CONCLUSIONS: Short-term, in vitro exposure to clinically-relevant concentrations of ALM solution had no adverse inflammatory or chondrotoxic effects on human chondro-MSC, with responses comparable to saline and TXA. These findings provide support for continued evaluation of ALM solution as a possible therapeutic to improve outcomes following orthopaedic procedures.

Tranexamic acid is associated with selective increase in inflammatory markers following total knee arthroplasty (TKA): a pilot study.

BACKGROUND: Tranexamic acid (TXA) is commonly used in orthopedic surgery to reduce excessive bleeding and transfusion requirements. Our aim was to examine if TXA was required in all osteoarthritis patients undergoing TKA surgery, and its possible effects on systemic inflammation and coagulation properties. METHODS: Twenty-three patients (Oxford Score 22-29) were recruited consecutively; 12 patients received TXA before (IV, 1.2 g/90 kg) and immediately after surgery (intra-articular, 1.4 g/90 kg). Inflammatory mediators and ROTEM parameters were measured in blood at baseline, after the first bone-cut, immediately after surgery, and postoperative days 1 and 2. RESULTS: After the bone cut and surgery, TXA significantly increased MCP-1, TNF-α, IL-1ß and IL-6 levels compared to non-TXA patients, which was further amplified postoperatively. During surgery, TXA significantly prolonged EXTEM clot times, indicating a thrombin-slowing effect, despite little or no change in clot amplitude or fibrinogen. TXA was associated with three- to fivefold increases in FIBTEM maximum lysis (ML), a finding counter to TXA's antifibrinolytic effect. Maximum lysis for extrinsic and intrinsic pathways was < 8%, indicating little or no hyperfibrinolysis. No significant differences were found in postoperative hemoglobin between the two groups. CONCLUSIONS: TXA was associated with increased systemic inflammation during surgery compared to non-TXA patients, with further amplification on postoperative days 1 and 2. On the basis of little or no change in viscoelastic clot strength, fibrinogen or clot lysis, there appeared to be no clinical justification for TXA in our group of patients. Larger prospective, randomized trials are required to investigate a possible proinflammatory effect in TKA patients.

Determination of the Accuracy of Navigated Kinematic Unicompartmental Knee Arthroplasty: A 2-Year Follow-Up.

BACKGROUND: Unicompartmental knee arthroplasty (UKA) lacks history of patient satisfaction and research addressing technique validity. The aim of this study was to determine minimally invasive navigated kinematic UKA accuracy by comparing postoperative limb alignment with preoperative stress values. METHODS: A single-center retrospective study was conducted on 53 consecutive patients (postoperative alignment: varus n = 51, valgus n = 2) who underwent computer navigation assisted UKA. Two patient groups (A and B) predetermined by joint deformity cut-off points (B included valgus deformity) underwent preoperative magnetic resonance imaging and x-ray evaluation to assess limb alignment and exclude lateral and patellofemoral osteoarthritis. Preoperative and postoperative joint alignment, stress value, and range of movement were recorded with navigation. Outcome measures include comparison of postoperative alignment to the preoperative stress values for varus and valgus postoperative alignment groups and preoperative and/or postoperative Western Ontario and McMaster Universities and Knee Society Score evaluations. RESULTS: Minor systematic bias was found between stress value and postoperative alignment; however, the magnitude of difference was clinically acceptable. Score evaluations, prosthesis size or alignment didn't differ between groups. Furthermore, there was no significant increase in range of movement at 2 years. There was a high degree of agreement between stress value and postoperative alignment values suggesting strong validity for the surgical technique to determine optimal postoperative alignment. CONCLUSION: This study validates our surgical technique. Minimally invasive navigated UKA allows us to predict predisease alignment and recreates it with high accuracy. Our clinical results at 2 years are comparable with other published data.

Closed Incision Negative Pressure Wound Therapy vs Conventional Dry Dressings After Primary Knee Arthroplasty: A Randomized Controlled Study.

BACKGROUND: The purpose of this study was to assess the effect of negative pressure wound therapy (NPWT) on quality of life (QoL), wound complications, and cost after primary knee arthroplasty. METHODS: A prospective analysis of 33 patients undergoing primary knee arthroplasty performed by 3 surgeons in one institution. The first 12 patients (3 bilateral and 9 unilateral) had conventional dry dressings (CDD) applied and cost of dressings was assessed. The other 21 patients all underwent bilateral knee arthroplasty and had either side randomized to receiving NPWT or CDD. Cost of dressings, wound complications, and QoL were compared. RESULTS: One patient had a reaction to the NPWT requiring readmission. Another had persistent wound drainage that required NPWT application. There were no wound issues in the remaining 31 patients. The average cost in the first 12 patients was Australian dollar $48.70 with an average of 1.5 changes on ward. In the 21 patients receiving both dressings, the average cost for CDD was less (Australian dollar $43.51 vs $396.02, P ≤ .011, effect size [ES] = 1.06). When comparing QoL factors, wound leakage (0.14 vs 0.39 P = .019, ES = 1.02), and wound protection (0.16 vs 0.33, P = .001, ES = 0.021) were better in the NPWT group. There was no other significant difference in QoL factors. The average number of changes on the ward was less for the NPWT group (1.19 vs 1.38, P = .317, ES = 1.02). CONCLUSION: We found no benefit in wound healing or cost with NPWT post knee arthroplasty. There was some benefit in NPWT QoL factors less wound leakage and better protection.