AdipoRon reduces TGFß1-mediated collagen deposition in vitro and alleviates knee stiffness in vivo.

Arthrofibrosis, which causes joint motion restrictions, is a common complication following total knee arthroplasty (TKA). Key features associated with arthrofibrosis include myofibroblast activation, knee stiffness, and excessive scar tissue formation. We previously demonstrated that adiponectin levels are suppressed within the knee tissues of patients affected by arthrofibrosis and showed that AdipoRon, an adiponectin receptor agonist, exhibited anti-fibrotic properties in human mesenchymal stem cells. In this study, the therapeutic potential of AdipoRon was evaluated on TGFß1-mediated myofibroblast differentiation of primary human knee fibroblasts and in a mouse model of knee stiffness. Picrosirius red staining revealed that AdipoRon reduced TGFß1-induced collagen deposition in primary knee fibroblasts derived from patients undergoing primary TKA and revision TKA for arthrofibrosis. AdipoRon also reduced mRNA and protein levels of ACTA2, a key myofibroblast marker. RNA-seq analysis corroborated the anti-myofibrogenic effects of AdipoRon. In our knee stiffness mouse model, 6 weeks of knee immobilization, to induce a knee contracture, in conjunction with daily vehicle (DMSO) or AdipoRon (1, 5, and 25 mg/kg) via intraperitoneal injections were well tolerated based on animal behavior and weight measurements. Biomechanical testing demonstrated that passive extension angles (PEAs) of experimental knees were similar between vehicle and AdipoRon treatment groups in mice evaluated immediately following immobilization. Interestingly, relative to vehicle-treated mice, 5 mg/kg AdipoRon therapy improved the PEA of the experimental knees in mice that underwent 4 weeks of knee remobilization following the immobilization and therapy. Together, these studies revealed that AdipoRon may be an effective therapeutic modality for arthrofibrosis.

Cost and outcomes of Hospital-based Usual cAre versus Tele-monitor self-directed Rehabilitation (HUATR) in patients with total knee arthroplasty: A randomized, controlled, non-inferiority trial.

OBJECTIVE: To evaluate the clinical efficacy and cost-effectiveness of telemonitored self-directed rehabilitation (TR) compared with hospital-based rehabilitation (HBR) for patients with total knee arthroplasty (TKA). DESIGN: In this randomized, non-inferiority clinical trial, 114 patients with primary TKA who were able to walk independently preoperatively were randomized to receive HBR (n = 58) or TR (n = 56). HBR comprised at least five physical therapy sessions over 10 weeks. TR comprised a therapist-led onboarding session, followed by a 10-week unsupervised home-based exercise program, with asynchronous monitoring of rehabilitation outcomes using a telemonitoring system. The primary outcome was fast-paced gait speed at 12 weeks, with a non-inferiority margin of 0.10 m/s. For economic analysis, quality-adjusted-life-years (QALY) was the primary economic outcome (non-inferiority margin, 0.027 points). RESULTS: In Bayesian analyses, TR had >95% posterior probability of being non-inferior to HBR in gait speed (week-12 adjusted TR-HBR difference, 0.02 m/s; 95%CrI, -0.05 to 0.10 m/s; week-24 difference, 0.01 m/s; 95%CrI, -0.07 to 0.10 m/s) and QALY (0.006 points; 95%CrI, -0.006 to 0.018 points). When evaluated from a societal perspective, TR was associated with lower mean intervention cost (adjusted TR-HBR difference, -S$227; 95%CrI, -112 to -330) after 24 weeks, with 82% probability of being cost-effective compared with HBR at a willingness to pay of S$0/unit of effect for the QALYs. CONCLUSIONS: In patients with uncomplicated TKAs and relatively good preoperative physical function, home-based, self-directed TR was non-inferior to and more cost-effective than HBR over a 24-week follow-up period. TR should be considered for this patient subgroup.

Outcomes of different perioperative management strategies of patients on chronic anticoagulation in elective total hip and knee arthroplasty: a systematic review.

INTRODUCTION: There are currently different management guidelines for patients undergoing elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) that are on long-term anticoagulation. The timing of discontinuation and restarting the anticoagulation is challenging during the postoperative care, which often involves general practitioners and physiotherapists. METHODS: The systematic review followed the PRISMA guidelines and included 3 databases: PubMed/MEDLINE, EMBASE, and Web of Science Core Collection. It was registered in the International Prospective Register for Systematic Reviews and Meta-analysis (PROSPERO) under the registration number: CRD42023408906. The risk of bias assessment was performed using the Methodological index for non-randomized studies (MINORS) criteria. RESULTS: Six retrospective studies involving 727 patients with therapeutic anticoagulation (1,540 controls) for elective THA, TKA and revision arthroplasty have been included. The follow-up ranged from 30 days to 1 year postoperatively. All studies evaluated outcomes of warfarin therapeutic anticoagulation versus prophylactic dosages of one or more of the following: warfarin, aspirin, low-molecular-weight heparin (LMWH) and unfractionated low-dose heparin (UFH). One study did not discontinue therapeutic anticoagulation. Two studies reported no significant differences in complications between groups, whilst 3 studies had significantly higher rates of superficial wound infections, revision surgeries, postoperative haematomas, and prosthetic joint infections (PJI). CONCLUSION: Different anticoagulation-related perioperative management strategies achieve different outcomes following elective arthroplasty in patients with therapeutic chronic anticoagulation. There is contradictory evidence regarding the need for the discontinuation of therapeutic warfarin. Retrospective data showed that individual risk stratification with multi-modal prophylaxis resulted in minimal complications. LEVEL OF EVIDENCE: Systematic Review of Level III studies.

Effect of adductor canal block combined with infiltration between the popliteal artery and posterior capsular of the knee on chronic pain after total knee arthroplasty: a prospective, randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Total knee arthroplasty (TKA) is accompanied by severe postoperative pain, which is reported to be an important cause of chronic pain. Ultrasound-guided adductor canal block (ACB) combined with infiltration between the popliteal artery and posterior capsular of the knee (IPACK) has been proven to have a better effect on relieving acute pain after TKA. However, whether it has a significant effect on the incidence of chronic pain after TKA has not been reported. This trial was designed to investigate the effect of ultrasound-guided ACB combined with IPACK on the incidence and intensity of chronic pain after TKA. METHODS: In this prospective, randomized, double-blind, placebo-controlled study, 100 subjects scheduled for TKA were randomly (1:1) divided into two groups: the ropivacaine group and the placebo group. Patients in each group received ultrasound-guided ACB + IPACK procedures with 0.25% ropivacaine or equal volume normal saline. All patients received multimodal analgesia. Pain intensity was assessed using the Numerical Rating Scale (NRS). The primary outcome was the incidence of chronic pain at 3 months after TKA by telephone follow-up. In addition, pain intensity in early resting and mobilized states, chronic pain intensity, the time to first rescue analgesia; opioid consumption; CRP and IL-6 after the operation; length of postoperative hospital stay; and cost of hospitalization and postoperative complications; as well as the function of the knee in the early stage after the operation, were recorded. RESULTS: Ninety-one participants were included in the final analysis. At 3 months, the incidence of chronic pain was 30.4% in the ropivacaine group, significantly lower than 51.1% in the placebo group. Compared with the placebo group, the ACB + IPACK with ropivacaine group had significantly lower pain scores at 4 hours, 8 hours, 16 hours, and 24 hours after the operation; increased the knee range of motion at 8 hours and 24 hours after the operation; and a significantly decreased incidence of chronic pain at 3 months after the operation. During the follow-up period, there were no nerve block-related complications in either group. CONCLUSION: In the context of multimodal analgesia protocols, ACB combined with IPACK before surgery decreases the incidence and intensity of chronic pain 3 months after TKA compared with placebo injection. In addition, it reduces the NRS scores, whether at rest or during mobilization, and improves knee function within 24 hours after TKA. TRIAL REGISTRATION: This trial was registered in the China Clinical Trial Center (registration number ChiCTR2200065300) on November 1, 2022.

The efficacy and safety of perioperative glucocorticoid for total knee arthroplasty: a systematic review and meta-analysis.

BACKGROUND: An increasing number of individuals undergo total knee arthroplasty (TKA), which can result in pain, limited motor function and adverse complications such as infection, nausea and vomiting. Glucocorticoids have been shown anti-inflammatory and antiemetic effects, but can also elevate blood glucose levels and increase the risk of wound infection. Thus, it is essential to investigate the efficacy and safety of glucocorticoid usage in TKA. METHOD: A comprehensive systematic search of PubMed, Medline, EMBASE, Cochrane databases, to identify relevant randomized controlled trials (RCTs) of glucocorticoid application in TKA. The primary outcomes assessed were the postoperative pain assessment. Secondary outcomes included the range of motion in knee joint, levels of inflammatory cytokines, adverse complications, and the length of hospital stay. RESULTS: Thirty-six randomized controlled trials were included in the final analysis. The glucocorticoid group exhibited significant reduction in the resting VAS scores on postoperative days 1, 2 (POD1, 2)and postoperative 3 months (POM3), as well as decreased morphine consumption on POD1 and increased range of motion (ROM) in knee joint on POD1, 3. Additionally, the glucocorticoid group exhibited decreased levels of postoperative inflammatory cytokines and the incidence of PONV along with a shorter length of hospital stay. The blood glucose concentration was significantly increased in the glucocorticoid group on POD1 compared with the control group. While the blood glucose on POD2 and occurrence of postoperative adverse complications were similar between two groups including wound infection and venous thrombosis. The periarticular injection analgesia (PIA) group demonstrated lower VAS scores on POD2 comparing to the systemic administration (SA) group according to two studies. However, there was no significant difference of the resting VAS on POD1 and POD2 between PIA and SA group across all studies. CONCLUSION: Perioperative glucocorticoids treatment in TKA significantly reduced short-term pain score and opioid-use which was probably not patient relevant. The application of glucocorticoids in TKA implied a beneficial trend in analgesic, anti-inflammatory, and antiemetic effects, as well as improved range of motion and shortened hospital stay. While it will not increase the risk of continued high glucose, postoperative wound infection and venous thrombosis.

A systematic review and meta-analysis of hybrid vs. cemented stems - which method is more optimal for revision total knee arthroplasty?

INTRODUCTION: The number of primary and revision Total Knee Arthroplasty (TKA) cases are expected to increase in future. There are various advantages and disadvantage to employing either of the two main types of stem fixation methods - cemented or hybrid technique. This review aimed to study the most optimal fixation method for revision TKAs by comparing radiological outcomes and re-revision rates. METHODS: A systematic review and meta-analysis was performed using PubMed and Cochrane Library from 2010 to identify studies explicitly comparing outcomes between cemented against hybrid fixation revision TKA techniques, with a minimum follow up of at least 24 months. A total of 8 studies was included in this review. Egger's test and visual inspection of the funnel plot did not reveal publication bias. RESULTS: There was no statistically significant difference in radiological failure and loosening (OR 0.79, CI 0.37-1.66, I2 = 29%, p = 0.22), all causes of re-revision (OR 1.03, CI 0.73-1.44, I2 = 0%, p = 0.56) and aseptic revision (OR 0.74, CI 0.27-2.02, I2 = 0%, p = 0.41) between cemented and hybrid techniques. Functional and pain outcomes compared between the two fixation techniques were largely similar across the studies included in this meta-analysis. CONCLUSION: Despite a trend favouring hybrid stems in revision TKA, current evidence revealed that radiological outcomes and re-revision rates are largely similar between cemented and hybrid fixation techniques.

Tourniquet does not affect intraoperative kinematics during total knee arthroplasty: Results of a prospective study using a robotic assistance system.

PURPOSE: Tourniquet use during total knee arthroplasty (TKA) remains controversial. There are limited data demonstrating the effect of tourniquet use on flexion and extension gaps. The use of a tourniquet can theoretically affect the kinematics of the knee joint, specifically the extension and flexion gaps and the laxity, by mechanically compressing the soft tissues including the muscles above the knee joint. Therefore, this study was designed to prospectively evaluate changes in flexion and extension gaps with and without the use of a tourniquet. METHODS: The following prospective study included 50 consecutive patients who underwent TKA using a surgical robot. The inclusion criteria were advanced osteoarthritis (OA) and varus-alignment or valgus-alignment <3° (hip-knee-ankle angle, standing long-leg X-ray), and the exclusion criteria were BMI >35 kg/m2 and mechanical axis in >3° valgus. A CR-TKA was performed, and the medial and lateral gaps (in mm) throughout the full range of motion in 10° increments were recorded. The procedure was conducted both with and without an applied tourniquet (350 mmHg). RESULTS: No significant differences were observed in the medial joint space. By contrast, the lateral gap showed significant differences in 10-20° of flexion (with a tourniquet 1.9 mm vs. without a tourniquet 2.1 mm, p = 0.018), 20-30° (1.6 vs. 1.8 mm, p = 0.02), 100-110° (0.9 vs. 1.1 mm, p = 0.021), and 110-120° (0.8 vs. 1 mm, p = 0.038). Thus, at the above degrees of flexion on the lateral side, there was a decrease in the mean of 0.2 mm with the use of a tourniquet. CONCLUSION: Although the use of a tourniquet showed a detectable change in the lateral gap in four 10° segments of flexion, clinical relevance with an average difference of 0.2 mm is not achieved. Thus, the use of a tourniquet in TKA can still be advocated based on the presented data. LEVEL OF EVIDENCE: Level I.

Inverse kinematic total knee arthroplasty using conventional instrumentation restores constitutional coronal alignment.

PURPOSE: Restricted inverse kinematic alignment (iKA) is a contemporary alignment strategy for total knee arthroplasty (TKA), commonly performed with robotic assistance. While superior clinical results are reported for kinematic-type alignment strategies, registry data indicate no survivorship benefit for navigation or robotic assistance. This study aimed to determine the efficacy of an instrumented, restricted iKA technique for achieving patient-specific alignment. METHODS: Seventy-nine patients undergoing 84 TKAs (five bilateral procedures) using an iKA technique were included for preoperative and postoperative lower limb alignment analysis. The mean age was 66.5 (range: 43-82) with 33 male and 51 female patients. Artificial intelligence was employed for radiographic measurements. Alignment profiles were classified using the Coronal Plane Alignment of the Knee (CPAK) system. Preoperative and postoperative alignment profiles were compared with subanalyses for preoperative valgus, neutral and varus profiles. RESULTS: The mean joint-line convergence angle (JLCA) reduced from 2.5° to -0.1° postoperatively. The mean lateral distal femoral angle (LDFA) remained unchanged postoperatively, while the mean medial proximal tibial angle (MPTA) increased by 2.5° (p = 0.001). By preservation of the LDFA and restoration of the MPTA, the mean hip knee ankle angle (HKA) moved through 3.5° varus to 1.2° valgus. The CPAK system was used to visually depict changes in alignment profiles for preoperative valgus, neutral and varus knees; with 63% of patients observing an interval change in classification. CONCLUSION: Encouraged by the latest evidence supporting both conventional instrumentation and kinematic-type TKA strategies, this study describes how a restricted, conventionally instrumented iKA technique may be utilised to restore constitutional lower limb alignment. LEVEL OF EVIDENCE: Level III.

Individualised compared to off-the-shelf total knee arthroplasty results in lower and less variable patellar tilt.

PURPOSE: The purpose of this study was to compare postoperative patellar tilt at 4 months follow-up in a consecutive series of randomised patients that received individualised or off-the-shelf (OTS) primary total knee arthroplasty (TKA). The hypothesis was that patellar tilt would be lower and less variable in patients who received individualised TKA compared to patients who received OTS TKA. METHODS: A consecutive series of 385 patients randomised (1:1) to receive either OTS TKA or individualised TKA were analysed. Pre- and postoperative radiographs at 4 months were obtained of weight-bearing long leg, anterior-posterior and lateral knee views and a skyline view at 30° of flexion. Postoperative patellar tilt was measured between the anterior femoral line and patellar resection surface (ß) and the anterior femoral line and mediolateral patellar axis (σ). Postoperative patellar tilt (absolute value) was compared between the individualised and OTS TKA groups based on preoperative phenotypes of their femoral mechanical angle, tibial mechanical angle and hip-knee-ankle angle. Variability in postoperative patellar tilt was compared using the 95% confidence intervals (CIs). RESULTS: Comparisons of baseline patient characteristics revealed no difference between the individualised and OTS TKA groups. Comparison of absolute postoperative patellar tilt revealed significant differences between individualised and OTS TKA (|ß|, 1.0° ± 1.0° and 2.5° ± 2.2°, respectively, p < 0.001; |σ|, 1.7° ± 1.6° and 2.8° ± 2.3°, respectively, p < 0.001). The 95% CI of postoperative patellar tilt (|ß|) was narrower in patients that received individualised compared to OTS TKA (0.0° to 3.8° and 0.1° to 8.3°, respectively), irrespective of their preoperative phenotype. CONCLUSION: Patients who underwent individualised TKA had lower and less variable postoperative patellar tilt than those with OTS TKA, irrespective of preoperative phenotype. Individualised TKA allows the decoupling of the tibiofemoral and patellofemoral joints, replicating anatomical trochlear orientation and improving patellar tilt, which could facilitate better clinical outcomes. CLINICAL TRIAL REGISTRATION: This study constitutes a part of a larger registered randomised controlled trial comparing patient satisfaction following OTS versus individualised TKA (NCT04460989). LEVEL OF EVIDENCE: Level II.

Similar QALY gain in primary and revision knee arthroplasty: A cost analysis and Markov model.

PURPOSE: The aim of this study is to investigate the cost-effectiveness of revision total knee arthroplasty compared to primary total knee arthroplasty in terms of cost-per-quality-adjusted life year (QALY). METHODS: Data were retrieved for all primary and revision total knee replacement (TKA) procedures performed at a tertiary Swiss hospital between 2006 and 2019. A Markov model was created to evaluate revision risk and we calculated lifetime QALY gain and lifetime procedure costs through individual EuroQol 5 dimension (EQ-5D) scores, hospital costs, national life expectancy tables and standard discounting processes. Cost-per-QALY gain was calculated for primary and revision procedures. RESULTS: EQ-5D data were available for 1343 primary and 103 revision procedures. Significant QALY gains were seen following surgery in all cases. Similar, but significantly more QALYs were gained following primary TKA (PTKA) (5.67 ± 3.98) than following revision TKA (RTKA) (4.67 ± 4.20). Cost-per-QALY was €4686 for PTKA and €10,364 for RTKA. The highest average cost-per-QALY was seen in two-stage RTKA (€12,292), followed by one-stage RTKA (€8982). CONCLUSION: RTKA results in a similar QALY gain as PTKA. The costs of achieving health gain are two to three times higher in RTKA, but both procedures are highly cost-effective. LEVEL OF EVIDENCE: Economic level II.