Association Between Tranexamic Acid and Decreased Periprosthetic Joint Infection Risk in Patients Undergoing Total Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis of Over 2 Million Patients.

BACKGROUND: The purpose of this study was to perform a systematic review and meta-analysis to evaluate the association between tranexamic acid (TXA) use during primary total hip arthroplasty (THA) and primary total knee arthroplasty (TKA), and the risk of developing periprosthetic joint infection (PJI) after these procedures. METHODS: A systematic review was carried out from inception to October 17, 2022. There were 6 studies that were ultimately included in the meta-analysis. The association between the development of PJI and TXA was analyzed using odds ratios (ORs) with 95% confidence intervals (CIs) and estimates of risk difference (RD). Subgroup analysis was performed to evaluate only studies reporting out to 90 days of follow-up versus more than 90 days of follow-up. RESULTS: Among 2,098,469 arthroplasties, TXA utilization was associated with an overall lower risk of PJI (OR = 0.63 [95% CI 0.42 to 0.96], P < .001) and a 0.4% lower incidence of PJI (RD = -0.0038, 95% CI [-0.005 to -0.002], P < .001). When subgrouping the studies according to length of follow-up, TXA was associated with a lower risk of PJI (OR = 0.43 [95% CI 0.35 to 0.53], P < .001) and a 1% lower incidence of PJI (RD = -0.0095 [95% CI -0.013 to -0.005], P < .001) in patients followed for more than 90 days. CONCLUSIONS: This meta-analysis demonstrates that TXA use is associated with a reduced risk of PJI, with our RD analysis identifying an approximately 0.4% reduction in PJI rates with TXA use. These findings provide even more data to support the routine use of TXA during primary THA and primary TKA.

Incorporating Wearable Technology for Enhanced Rehabilitation Monitoring after Hip and Knee Replacement.

Osteoarthritis (OA) poses a growing challenge for the aging population, especially in the hip and knee joints, contributing significantly to disability and societal costs. Exploring the integration of wearable technology, this study addresses the limitations of traditional rehabilitation assessments in capturing real-world experiences and dynamic variations. Specifically, it focuses on continuously monitoring physical activity in hip and knee OA patients using automated unsupervised evaluations within the rehabilitation process. We analyzed data from 1144 patients who used a mobile health application after surgery; the activity data were collected using the Garmin Vivofit 4. Several parameters, such as the total number of steps per day, the peak 6-minute consecutive cadence (P6MC) and peak 1-minute cadence (P1M), were computed and analyzed on a daily basis. The results indicated that cadence-based measurements can effectively, and earlier, differ among patients with hip and knee conditions, as well as in the recovery process. Comparisons based on recovery status and type of surgery reveal distinctive trajectories, emphasizing the effectiveness of P6MC and P1M in detecting variations earlier than total steps per day. Furthermore, cadence-based measurements showed a lower inter-day variability (40%) compared to the total number of steps per day (80%). Automated assessments, including P1M and P6MC, offer nuanced insights into the patients' dynamic activity profiles.

Severe Postoperative Pain in Total Knee Arthroplasty Patients: Risk Factors, Insights and Implications for Pain Management via a Digital Health Approach.

Up to 25% of patients undergoing knee arthroplasty report chronic pain postoperatively. Early identification of high-risk individuals can enhance pain management strategies. This retrospective analysis investigates the incidence of severe postoperative pain and its associated risk factors among 740 patients who underwent total knee arthroplasty. Utilizing a digital application, patients provided comprehensive data encompassing pre- and postoperative pain levels, analgesic usage, and completed a chronic pain risk assessment. Participants were categorized into two distinct groups based on their pain status at three months post-op: Group D+ (14%), characterized by pain scores exceeding 40/100 and/or the utilization of level 2 or 3 analgesics, and Group D- (86%), who did not meet these criteria. An analysis of pain trajectories within these groups revealed a non-linear progression, with specific patterns emerging amongst those predisposed to chronic pain. Notably, patients with a trajectory towards chronic pain exhibited a plateau in pain intensity approximately three weeks post-surgery. Significant preoperative risk factors were identified, including elevated initial pain levels, the presence of comorbidities, pain in other body areas, heightened joint sensitivity and stiffness. This study highlights the utility of digital platforms in enhancing patient care, particularly through the continuous monitoring of pain. Such an approach facilitates the early identification of potential complications and enables timely interventions.

Development of an innovative in vivo model of PJI treated with DAIR.

Introduction: Prosthetic Joint Infection (PJI) are catastrophic complications of joint replacement. Debridement, implant retention, and antibiotic therapy (DAIR) is the usual strategy in acute infections but fails in 45% of MRSA infections. We describe the development of a model of infected arthroplasty in rabbits, treated with debridement and a course of vancomycin with clinically relevant dosage. Materials and methods: A total of 15 rabbits were assigned to three groups: vancomycin pharmacokinetics (A), infection (B), and DAIR (C). All groups received a tibial arthroplasty using a Ti-6Al-4V implant. Groups B and C were infected per-operatively with a 5.5 log10 MRSA inoculum. After 1 week, groups C infected knees were surgically debrided. Groups A and C received 1 week of vancomycin. Pharmacokinetic profiles were obtained in group A following 1st and 5th injections. Animals were euthanized 2 weeks after the arthroplasty. Implants and tissue samples were processed for bacterial counts and histology. Results: Average vancomycin AUC0-12 h were 213.0 mg*h/L (1st injection) and 207.8 mg*h/L (5th injection), reaching clinical targets. All inoculated animals were infected. CFUs were reproducible in groups B. A sharp decrease in CFU was observed in groups C. Serum markers and leukocytes counts increased significantly in infected groups. Conclusion: We developed a reproducible rabbit model of PJI treated with DAIR, using vancomycin at clinically relevant concentrations.

Hydrolytic Enzymes as Potentiators of Antimicrobials against an Inter-Kingdom Biofilm Model.

Biofilms are recalcitrant to antimicrobials, partly due to the barrier effect of their matrix. The use of hydrolytic enzymes capable to degrade matrix constituents has been proposed as an alternative strategy against biofilm-related infections. This study aimed to determine whether hydrolytic enzymes could potentiate the activity of antimicrobials against hard-to-treat interkingdom biofilms comprising two bacteria and one fungus. We studied the activity of a series of enzymes alone or in combination, followed or not by antimicrobial treatment, against single-, dual- or three-species biofilms of Staphylococcus aureus, Escherichia coli, and Candida albicans, by measuring their residual biomass or culturable cells. Two hydrolytic enzymes, subtilisin A and lyticase, were identified as the most effective to reduce the biomass of C. albicans biofilm. When targeting interkingdom biofilms, subtilisin A alone was the most effective enzyme to reduce biomass of all biofilms, followed by lyticase combined with an enzymatic cocktail composed of cellulase, denarase, and dispersin B that proved previously active against bacterial biofilms. The subsequent incubation with antimicrobials further reduced the biomass. Enzymes alone did not reduce culturable cells in most cases and did not interfere with the cidal effects of antimicrobials. Therefore, this work highlights the potential interest of pre-exposing interkingdom biofilms to hydrolytic enzymes to reduce their biomass besides the number of culturable cells, which was not achieved when using antimicrobials alone. IMPORTANCE Biofilms are recalcitrant to antimicrobial treatments. This problem is even more critical when dealing with polymicrobial, interkingdom biofilms, including both bacteria and fungi, as these microorganisms cooperate to strengthen the biofilm and produce a complex matrix. Here, we demonstrate that the protease subtilisin A used alone, or a cocktail containing lyticase, cellulase, denarase, and dispersin B markedly reduce the biomass of interkingdom biofilms and cooperate with antimicrobials to act upon these recalcitrant forms of infection. This work may open perspectives for the development of novel adjuvant therapies against biofilm-related infections.

Pharmacodynamics of Moxifloxacin, Meropenem, Caspofungin, and Their Combinations against In Vitro Polymicrobial Interkingdom Biofilms.

Biofilms colonize medical devices and are often recalcitrant to antibiotics. Interkingdom biofilms, where at least a bacterium and a fungus are present, increase the likelihood of therapeutic failures. In this work, a three-species in vitro biofilm model including Staphylococcus aureus, Escherichia coli, and Candida albicans was used to study the activity of the antibiotics moxifloxacin and meropenem, the antifungal caspofungin, and combinations of them against interkingdom biofilms. The culturable cells and total biomass were evaluated to determine the pharmacodynamic parameters of the drug response for the incubation with the drugs alone. The synergic or antagonistic effects (increased/decreased effects) of the combination of drugs were analyzed with the highest-single-agent method. Biofilms were imaged in confocal microscopy after live/dead staining. The drugs had limited activity when used alone against single-, dual-, and three-species biofilms. When used in combination, additive effects against single- and dual-species biofilms and increased effects (synergy) against biomass of three-species biofilms were observed. In addition, the two antibiotics showed different patterns, moxifloxacin being more active when targeting S. aureus and meropenem when targeting E. coli. All these observations were confirmed by confocal microscopy images. Our findings highlight the interest in combining caspofungin with antibiotics against interkingdom biofilms.

In vitro polymicrobial inter-kingdom three-species biofilm model: influence of hyphae on biofilm formation and bacterial physiology.

Biofilms are an important medical burden, notably for patients with orthopaedic device-related infections. When polymicrobial, these infections are more lethal and recalcitrant. Inter-kingdom biofilm infections are poorly understood and challenging to treat. Here, an in vitro three-species model including Staphylococcus aureus, Escherichia coli and Candida albicans was developed, to represent part of the diversity observed in orthopaedic infections or other clinical contexts. The importance of fungal hyphae for biofilm formation and virulence factor expression was explored. Two protocols were set up, allowing, or not, for hyphal formation. Culturable cells and biomass were characterised in both models, and biofilms were imaged in bright-field, confocal and electron microscopes. The expression of genes related to virulence, adhesion, exopolysaccharide synthesis and stress response was analysed in early-stage and mature biofilms. It was found that biofilms enriched in hyphae had larger biomass and showed higher expression levels of genes related to bacterial virulence or exopolysaccharides synthesis.

In Vitro Study of the Synergistic Effect of an Enzyme Cocktail and Antibiotics against Biofilms in a Prosthetic Joint Infection Model.

Prosthetic joint infections (PJI) are frequent complications of arthroplasties. Their treatment is made complex by the rapid formation of bacterial biofilms, limiting the effectiveness of antibiotic therapy. In this study, we explore the effect of a tri-enzymatic cocktail (TEC) consisting of an endo-1,4-ß-d-glucanase, a ß-1,6-hexosaminidase, and an RNA/DNA nonspecific endonuclease combined with antibiotics of different classes against biofilms of Staphylococcus aureus, Staphylococcus epidermidis, and Escherichia coli grown on Ti-6Al-4V substrates. Biofilms were grown in Trypticase soy broth (TSB) with 10 g/liter glucose and 20 g/liter NaCl (TGN). Mature biofilms were assigned to a control group or treated with the TEC for 30 min and then either analyzed or reincubated for 24 h in TGN or TGN with antibiotics. The cytotoxicity of the TEC was assayed against MG-63 osteoblasts, primary murine fibroblasts, and J-774 macrophages using the lactate dehydrogenase (LDH) release test. The TEC dispersed 80.3 to 95.2% of the biofilms' biomass after 30 min. The reincubation of the treated biofilms with antibiotics resulted in a synergistic reduction of the total culturable bacterial count (CFU) compared to that of biofilms treated with antibiotics alone in the three tested species (additional reduction from 2 to more than 3 log10 CFU). No toxicity of the TEC was observed against the tested cell lines after 24 h of incubation. The combination of pretreatment with TEC followed by 24 h of incubation with antibiotics had a synergistic effect against biofilms of S. aureus, S. epidermidis, and E. coli Further studies should assess the potential of the TEC as an adjuvant therapy in in vivo models of PJI.

Predicting physical activity recovery after hip and knee arthroplasty? A longitudinal cohort study.

BACKGROUND: Recovery of physical activity (PA) after telerehabilitation following knee and hip arthroplasty (TKA-THA) has rarely been studied. An improved understanding of PA recovery is needed, as it could be influenced by many factors such as age, gender or pre-operative physical function. OBJECTIVES: To assess PA recovery weekly for 3 months after TKA-THA and to determine perioperative factors that could help predict PA recovery at 3 months. METHODS: From one week before until 3 months after surgery, 132 patients wore a fitness tracker continuously. Each patient received personalized and daily exercises and feedback through a tablet. Before and after surgery, patient-reported outcome measures of symptoms, pain, activities of daily living and quality of life were recorded. A one-way repeated-measure ANOVA was used to assess the time effect on step count for each post-operative week. To predict the absolute step count at 3 months post-surgery, a backward multiple linear regression was used. RESULTS: Patients reached their pre-operative PA level at week 7, with no significant additional improvement by 3 months post-surgery. Pre-operative step count, the number of days using crutches and pre-operative symptoms explained 35% of the variability of step count at 3 months. CONCLUSION: This patient population receiving telerehabilitation reached their pre-operative PA level at 7-week post-surgery with no further improvement over the subsequent 5 weeks. The PA level at 3 months could be predicted by pre-operative step count, duration of crutches use, and pre-operative symptoms.

Synergistic Effects of Pulsed Lavage and Antimicrobial Therapy Against Staphylococcus aureus Biofilms in an in-vitro Model.

Background: Prosthetic joint infections (PJI) are difficult to treat complications of joint arthroplasty. Debridement with implant retention is a common treatment strategy and frequently involves the use of pulsed lavage (PL). However, PL effects on biofilms and antibiotic activity have been scarcely studied in-vitro. We report the effects of PL, vancomycin or flucloxacillin used independently or in combination against Staphylococcus aureus biofilms. Methods: Biofilms of 3 methicillin-susceptible (MSSA) and of 3 methicillin-resistant (MRSA) S. aureus were grown on Ti6Al4V coupons in TGN (TSB + 1%glucose + 2%NaCl). After 24 h, PL was applied to half of the samples (50 mL saline from 5 cm). Samples were either reincubated for 24 h in TGN or TGN + flucloxacillin or vancomycin. Analyses included CFUs counts, biomass assays or fluorescence microscopy. Results: PL transiently reduced bacterial counts by 3-4 Log10 CFU/coupon, but bacterial regrowth to baseline levels was seen after 24 h. At 20 mg/L, flucloxacillin reduced both the CFU counts (3 Log10 CFU/coupon) and biomass (-70%) in one MSSA only, while vancomycin had no effects against MRSA. PL combined with a 24 h reincubation with vancomycin or flucloxacillin at 20 mg/L was synergistic (-5 to 6.5 Log10 CFU/coupon; 81-100% biomass reduction). Fluorescence microscopy confirmed that PL removed most of the biofilm and that subsequent antibiotic treatment partially killed bacteria. Conclusions: While PL only transiently reduces the bacterial load and antibiotics at clinically relevant concentrations show no or limited activity on biofilms, their combination is synergistic against MRSA and MSSA biofilms. These results highlight the need for thorough PL before antibiotic administration in PJI.

Alpha Defensin: A Diagnostic Accuracy Depending on the Infection Definition Used.

BACKGROUND: The purpose of this study was to evaluate the alpha defensin qualitative detection (ADLF) sensitivity and specificity as compared with 3 standard classifications in the diagnostic management of chronic prosthetic joint infections. MATERIALS AND METHODS: A multicenter cohort of 136 patients with a painful arthroplasty was classified into either infected or noninfected according to the Musculoskeletal Infection Society (MSIS) score, Infectious Diseases Society of America (IDSA) score, European Bone and Joint Infection Society (EBJIS) score. The sensitivity and specificity of the ADLF test were calculated for each score. Spearman's correlations between all scores were then analyzed, and multiple logistic regression was applied to identify independent variables strongly connected to the prosthetic joint infection probability. RESULTS: The EBJIS score was positive in 68 patients, IDSA score in 50 patients, MSIS score in 41 patients, and ADLF in 40 patients. The ADLF sensitivity was 87.8% compared with MSIS, 70% compared with IDSA, and 55.8% compared with EBJIS. The ADLF specificity was in the range of 94%-97%. A good correlation was observed between synovial fluid cultures and ADLF (r = 0.73). Low to excellent correlations were recorded between ADLF and the EBJIS (r = 0.58), IDSA (r = 0.68), and MSIS (r = 0.84) scores. The synovial fluid's white blood cell count was proven to be the biological test that most influenced the probability of a positive culture (P value: .005). DISCUSSION: The ADLF sensitivity was variable, whereas its specificity was excellent. The EBJIS score results significantly differed from those obtained via cultures, which possibly explains the ADLF low sensitivity compared with that of the EBJIS score.

Debridement, antibiotics, irrigation and retention in prosthetic joint infection : predictive tools of failure.

Debridement, antibiotic, irrigation and retention of the implant (DAIR) is an attractive treatment for periprosthetic joint infection (PJI). The purpose of this study is to determine predictive factors of failure. We reviewed all DAIR procedures for hip PJI performed between 2002-2017 (n=69). Data recorded included all factors correlated with treatment failure. KLIC score, McPherson adapted score were analyzed. Infection eradication for early PJI (< 4 weeks) was achieved in 68% of patients and was correlated with treatment success (p=0.01). KLIC score (p=0.036), McPherson adapted score (p=0.01), CRP (p=0.025) and late PJI (p=0.031) were significantly predictive of failure treatment. We have established an equation in order to predict failure treatment that has to be validated. DAIR is an effective treatment for early PJI. KLIC score and McPherson adapted score are two ways to predict outcome of a DAIR procedure and should help making the decision in PJI treatment.

Delayed total hip arthroplasty infection with Mycobacterium Tuberculosis complex.

Total Hip Arthroplasty (THA) joint infection is an uncommon (0,3-1,7%) (20) but devastating complication after THA. While mostly caused by Gram-positive bacteria, with staphylococci and streptococci accounting for up to 76% of cases (21), orthopaedic surgeons are sometimes faced with atypical germs such as fungi or mycobacteria. We present a case of THA joint infection caused by Mycobacterium tuberculosis (MT) in a patient without a previous history of MT infection. A literature review was performed, and the treatment is discussed.

Galactosyl-knock-out engineered pig as a xenogenic donor source of adipose MSCs for bone regeneration.

Pig adipose mesenchymal stem cells (AMSCs) could be proposed for the improvement of bone substitute. However, these xenogenic cells retain a galactosyl (Gal) epitope that elicits xenorejection. Our work aims to use Gal-Knock-Out (Gal-KO) pig AMSCs to associate cellular immunomodulation, humoral down-elicitation of Gal-KO cells and osteogenic capacity of AMSCs. Human and pig AMSCs were compared for proliferation/differentiation kinetics and bone neoformation in vivo. Humoral reaction against pig Gal+ vs. Gal-KO AMSCs and immunomodulation properties of Gal+ vs. Gal-KO AMSCs were assessed in vitro. Humoral/cellular reactions against Gal+ vs. Gal-KO osteogenic differentiated pig AMSC xenografts were assessed in an immunocompetent rodent model. Expansion/differentiation/bone neoformation was significantly improved with differentiated pig AMSCs compared with human cells. Based on immunohistochemistry and cell-based ELISA, Gal+ AMSCs had higher sensitivity to preformed/induced anti-pig antibodies than Gal-KO AMSCs. In vitro cellular immunomodulation was similar between Gal+ and Gal-KO AMSCs. In vivo, a significant reduction of anti-pig IgG was found at 1 month in rats implanted with Gal-KO AMSCs compared with those implanted with Gal+ AMSCs. Lymphocyte/macrophage infiltration of osteogenic differentiated pig AMSC xenografts was significantly lower at post-operative day (POD) 7 in recipients of Gal-KO vs. Gal+ pig cells. No significant difference was found at POD 28. The combination of the cellular immunomodulation with the Gal-KO phenotype of AMSCs can significantly improve the cellular engraftment of pig osteogenic cells by delaying xenorejection.