Risk factors for failure of manipulation under anesthesia after total knee arthroplasty.

BACKGROUND: Manipulation under anesthesia (MUA) is a well-established treatment for stiffness after total knee arthroplasty (TKA). Risk factors for failure of MUA remain largely unknown. The primary aim of this study was to identify risk factors for failure of MUA after TKA. METHODS: We performed a retrospective cohort study including 470 patients who underwent MUA after primary TKA with minimum 2 year follow-up. Patients were grouped into success (n = 412) or failure (n = 58) cohorts; failure was defined as flexion < 90° at most recent follow-up or revision for stiffness. The increase in flexion post-MUA for the cohort was calculated. Several clinical, patient, and surgical factors were analyzed using univariate, followed by multivariable logistic regression models to identify independent risk factors associated with failure. RESULTS: The mean increase in flexion was 42° (range 0-115). BMI 30-35 (p = 0.01, odds ratio (OR) 2.42; 95% CI 1.25-4.68) and poorer pre-MUA flexion (p < 0.01, OR 1.43; 95% CI 1.23-1.67) were risk factors for failure. When considering revision for stiffness only, BMI 30-35 (p = 0.01, OR 3.27; 95% CI 1.41-7.61), lower pre-MUA flexion (p < 0.01, OR 1.43; 95% CI 1.18-1.75), and history of prior knee surgery (p = 0.04, OR 2.31; 95% CI 1.06-5.04) were predictors of failure. Time to MUA (p = 0.48), thromboprophylaxis (p = 0.44), pre-operative opioid use (p = 0.34), depression/anxiety (p = 1.0), and several other factors analyzed were not associated with failure. CONCLUSION: In this large cohort, elevated BMI and lower pre-MUA flexion were risk factors for failure of MUA. History of prior knee surgery was an additional predictor of requiring revision for stiffness.

Biomechanical outcomes of pharmacological therapies for post-traumatic arthrofibrosis in preclinical animal models: a systematic review and meta-analysis.

PURPOSE/AIM OF THE STUDY: There is still no evidence of which drug has the greatest therapeutic potential for post-traumatic arthrofibrosis. The aim of this study is to systematically review the literature for quality evidence and perform a meta-analysis about the pharmacological therapies of post-traumatic arthrofibrosis in preclinical models. MATERIALS AND METHODS: A comprehensive and systematic search strategy was performed in three databases (MEDLINE, EMBASE and Web of Science) retrieving studies on the effectiveness of pharmacological therapies in the management of post-traumatic arthrofibrosis using preclinical models in terms of biomechanical outcomes. Risk of bias assessment was performed using the SYRCLE's risk of bias tool. A meta-analysis using a random-effects model was conducted if a minimum of three studies reported homogeneous outcomes for drugs with the same action mechanism. RESULTS: Forty-six studies were included in the systematic review and evaluated for risk of bias. Drugs from 6 different action mechanisms of 21 studies were included in the meta-analysis. Overall, the methodological quality of the studies was poor. Statistically significant overall effect in favor of reducing contracture was present for anti-histamines (Chi2 p = 0.75, I2 = 0%; SMD (Standardized Mean Difference) = -1.30, 95%CI: -1.64 to -0.95, p < 0.00001) and NSAIDs (Chi2 p = 0.01, I2 = 63%; SMD= -0.93, 95%CI: -1.58 to -0.28, p = 0.005). CONCLUSIONS: Anti-histamines, particularly ketotifen, have the strongest evidence of efficacy for prevention of post-traumatic arthrofibrosis. Some studies suggest a potential role for NSAIDs, particularly celecoxib, although heterogeneity among the included studies is significant.

The association between losartan potassium prescription and postoperative outcomes following total knee arthroplasty: A TriNetX analysis.

BACKGROUND: Total knee arthroplasty (TKA) is a common surgical procedure performed to alleviate pain and improve functional outcomes in patients with knee osteoarthritis and rheumatoid arthritis who have failed conservative treatments. Arthrofibrosis has been extensively studied due to its negative impact on TKA outcomes. Losartan, an angiotensin receptor blocker (ARB), has the potential to improve TKA outcomes by inhibiting TGF-ß and decreasing fibrosis. This study aims to analyze a large-scale, real-world healthcare database to investigate the association between losartan potassium prescription and postoperative outcomes such as readmissions, ED visits, and the need for MUA or revision TKA. HYPOTHESIS: Based on previous literature and the nature of ARBs, it is expected that the addition of losartan will aid in better outcomes for patients following a primary TKA. PATIENTS AND METHODS: In this retrospective observational study, the TriNetX Research Network (TriNetX) database was queried as of June 21, 2023. All patients who underwent a primary total knee arthroplasty (TKA) prior to June 21, 2022 were included. Patients were then divided into two cohorts by whether they had an active losartan potassium prescription within the year prior to their surgery to within 90days postoperatively. Patients were then propensity-matched to eliminate differences in demographics and comorbidities. RESULTS: Losartan TKA patients were 1.18 [OR: 0.85 (95% CI: 0.79-0.90), p<0.001] times less likely to be readmitted within 90days and were 1.15 (OR: 0.87 (95% CI: 0.79-0.96); p=0.009) times less likely to undergo a manipulation under anesthesia (MUA) within the 1-year postoperative period. There were no statistically significant differences in rates of emergency department (ED) visits at 90days postoperatively or revision TKAs at 1year postoperatively. DISCUSSION: In conclusion, patients with an active losartan prescription prior to TKA had a significantly lower likelihood of readmission within 90days and a lower likelihood of undergoing MUA within the 1-year postoperative period compared to patients not taking losartan. This presents an opportunity for further clinical investigation to explore the value of losartan in TKA. LEVEL OF EVIDENCE: III; an observational cohort study.

The efficacy of vitamin E in preventing arthrofibrosis after joint replacement.

BACKGROUND: Arthrofibrosis is a joint disorder characterized by excessive scar formation in the joint tissues. Vitamin E is an antioxidant with potential anti-fibroblastic effect. The aim of this study was to establish an arthrofibrosis rat model after joint replacement and assess the effects of vitamin E supplementation on joint fibrosis. METHODS: We simulated knee replacement in 16 male Sprague-Dawley rats. We immobilized the surgical leg with a suture in full flexion. The control groups were killed at 2 and 12 weeks (n = 5 per group), and the test group was supplemented daily with vitamin E (0.2 mg/mL) in their drinking water for 12 weeks (n = 6). We performed histological staining to investigate the presence and severity of arthrofibrosis. Immunofluorescent staining and α2-macroglobulin (α2M) enzyme-linked immunosorbent assay (ELISA) were used to assess local and systemic inflammation. Static weight bearing (total internal reflection) and range of motion (ROM) were collected for functional assessment. RESULTS: The ROM and weight-bearing symmetry decreased after the procedure and recovered slowly with still significant deficit at the end of the study for both groups. Histological analysis confirmed fibrosis in both lateral and posterior periarticular tissue. Vitamin E supplementation showed a moderate anti-inflammatory effect on the local and systemic levels. The vitamin E group exhibited significant improvement in ROM and weight-bearing symmetry at day 84 compared to the control group. CONCLUSIONS: This model is viable for simulating arthrofibrosis after joint replacement. Vitamin E may benefit postsurgical arthrofibrosis, and further studies are needed for dosing requirements.

Arthroscopic Arthrolysis of Knee: Timing, Technique and Results.

Aim: To evaluate the functional outcomes of patients undergoing arthroscopic arthrolysis of the knee and find the ideal timing for arthrolysis to achieve maximum range of motion (ROM) of the knee. Methods: All patients who underwent arthroscopic arthrolysis for post-operative joint stiffness following surgery for injuries around knee joint at a tertiary care centre from 2009 to 2023 were included in this study. The patients' details such as primary injury, time interval between the index surgery and arthrolysis, improvement in knee range of ROM and Lysholm score from prior to arthrolysis to last follow-up post arthrolysis were retrieved from hospital database and analysed. Results: Total of 42 patients who underwent arthroscopic arthrolysis of knee from 2009 to 2023 were included in this study. Follow-up range was 6 months to 6 years. ROM after arthrolysis significantly improved in the early and delayed arthrolysis groups as compared to late arthrolysis groups (mean 126.25 and 115.62 vs 106.3, p < 0.05). Patients treated with early arthroscopic arthrolysis (within 3 months) showed significant increase in post operative Lysholm score compared to other groups (p < 0.05). ROM of 120° and beyond was achieved in 75% of cases in early arthrolysis group compared to 62.8% and 39% in delayed and late arthrolysis group (p < 0.05). Conclusions: Arthroscopic arthrolysis done within 6 months (with maximum effect when done within 3 months) after the primary surgery leads to significant improvement in ROM and functional scores as compared to those with late arthrolysis group.

The Chitranjan S. Ranawat Award: Manipulation Under Anesthesia to Treat Postoperative Stiffness After Total Knee Arthroplasty: A Multicenter Randomized Clinical Trial.

BACKGROUND: Manipulation under anesthesia (MUA) occurs in 4% of patients after total knee arthroplasty (TKA). Anti-inflammatory medications may target arthrofibrosis pathogenesis, but the data are limited. This multicenter randomized clinical trial investigated the effect of adjuvant anti-inflammatory medications with MUA and physical therapy on range of motion (ROM) and outcomes. METHODS: There were 124 patients (124 TKAs) who developed stiffness after primary TKA for osteoarthritis enrolled across 15 institutions. All received MUA when ROM was < 90° at 4 to 12 weeks postoperatively. Randomization proceeded via a permuted block design. Controls received MUA and physical therapy, while the treatment group also received one dose of pre-MUA intravenous dexamethasone (8 mg) and 14 days of oral celecoxib (200 mg). The ROM and clinical outcomes were assessed at 6 weeks and 1 year. This trial was registered with ClinicalTrials.gov. RESULTS: The ROM significantly improved a mean of 46° from a pre-MUA ROM of 72 to 118° immediately after MUA (P < .001). The ROM was similar between the treatment and control groups at 6 weeks following MUA (101 versus 99°, respectively; P = .35) and at one year following MUA (108 versus 108°, respectively; P = .98). Clinical outcomes were similar at both end points. CONCLUSIONS: In this multicenter randomized clinical trial, the addition of intravenous dexamethasone and a short course of oral celecoxib after MUA did not improve ROM or outcomes. However, MUA provided a mean ROM improvement of 46° immediately, 28° at 6 weeks, and 37° at 1 year. Further investigation in regards to dosing, duration, and route of administration of anti-inflammatory medications remains warranted. LEVEL OF EVIDENCE: Level 1, RCT.

Risk factors for reoperation for arthrofibrosis following primary anterior cruciate ligament reconstruction.

PURPOSE: The purpose of this study is to identify the rate and risk factors for a reoperation for arthrofibrosis following primary anterior cruciate ligament (ACL) reconstruction. METHODS: Prospective data recorded in the New Zealand ACL Registry were cross-referenced with data from the Accident Compensation Corporation (ACC). Primary ACL reconstructions performed between April 2014 and May 2021 were analysed. The ACC database was used to identify patients who underwent a reoperation for a diagnosis of arthrofibrosis. Multivariable survival analysis was performed to compute adjusted hazard ratios (aHR) and 95% confidence intervals. RESULTS: A total of 12,296 primary ACL reconstructions were analysed, of which 230 underwent a reoperation for arthrofibrosis (1.9%) at a mean follow-up of 3.6 years. A higher risk of arthrofibrosis was observed in females (aHR = 1.76, p = 0.001), patients with a history of previous knee surgery (aHR = 1.82, p = 0.04) and when a transtibial drilling technique was used (aHR = 1.53, p = 0.03). ACL reconstruction >6 months after injury had the lowest rate of arthrofibrosis (1.3%, aHR = 0.45, p = 0.01). There was no difference in risk between early surgery within 6 weeks versus delayed surgery between 6 weeks and 6 months after injury (2.9% versus 2.1%, aHR = 0.78, not significant). CONCLUSION: Female sex, previous knee surgery and a transtibial drilling technique increased the risk of reoperation for arthrofibrosis. Early surgery within 6 weeks of injury was not associated with an increased risk when compared with surgery between 6 weeks and 6 months after injury. LEVEL OF EVIDENCE: Level III.

Acute Anterior Cruciate Ligament Reconstruction Performed Within 10 Days of Injury Does Not Increase Risk of Postoperative Arthrofibrosis: A Systematic Review and Meta-analysis.

BACKGROUND: The optimal timing of anterior cruciate ligament (ACL) reconstruction (ACLR) remains a controversial topic. Previous reviews have demonstrated that there are no differences between early and delayed ACLR; however, these studies have been limited by heterogeneous definitions of acute ACL injury. PURPOSE: To evaluate postoperative patient functional outcomes and risk for arthrofibrosis after acute arthroscopic ACLR performed ≤10 days after injury. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines using multiple medical databases. Inclusion criteria were studies that evaluated postoperative range of motion outcomes for patients undergoing ACLR ≤10 days after initial ACL injury. For included comparative studies comparing patient groups undergoing ACLR ≤10 days and patients undergoing "delayed" ACLR after ≥3 weeks of initial injury, quantitative analysis was performed to assess for differences in postoperative arthrofibrosis, reoperation rates, and patient-reported outcomes between groups. DerSimonian-Laird binary random-effects models were constructed to quantitatively describe the association between the ACLR time period and patient outcomes by generating effect estimates in the form of odds ratios with 95% CIs. Qualitative analysis was performed to describe variably reported patient outcomes and the risk of arthrofibrosis after ACLR for noncomparative studies. RESULTS: Screening yielded 6 full-text articles with 448 patients who underwent ACLR (296 ACLR <10 days, 152 ACLR >3 weeks), with a pooled mean age of 28.1 years. For studies amenable to quantitative analysis, there were no significant differences between ACLR performed ≤10 days and ACLR performed at the 3-week point or after in terms of postoperative stiffness (3 studies; odds ratio, 1.27; P = .508), Tegner scores (2 studies; mean difference, -0.056; P = .155), or reoperation for stiffness (3 studies; odds ratio, 0.869; P = .462). The overall incidence of postoperative arthrofibrosis after 12 months of follow-up was 11 of 296 (3.7%) for ACLRs performed ≤10 days versus 6 of 152 (3.9%) for those performed at the 3-week point or after. CONCLUSION: ACLR performed ≤10 days after the inciting injury does not increase the risk of postoperative arthrofibrosis and demonstrates similar patient-reported outcomes compared with ACLR performed at the 3-week point or after.

Low-Dose Irradiation and Rotating-Hinge Revision for the Treatment of Severe Idiopathic Arthrofibrosis Following Total Knee Arthroplasty: A Review of 60 Patients With a Mean 6-Year Follow-Up.

BACKGROUND: Severe idiopathic arthrofibrosis after total knee arthroplasty (TKA) is a challenging problem to treat. Low-dose irradiation may decrease fibro-osseous proliferation, while rotating-hinge (RH) revision allows for distal femur shortening and collateral ligament sacrifice. This study reports the clinical outcomes and implant survivorship in patients treated with low-dose irradiation and RH revision for severe idiopathic arthrofibrosis following TKA. METHODS: A retrospective review was performed on 60 consecutive patients. Patients who had greater than 80° arc of knee motion or less than 15° flexion contracture were excluded. Mean follow-up was 6 years (range, 2 to 14). Kaplan-Meier survivorship analyses were performed, and logistic regressions were used to determine associations between preoperative patient characteristics and clinical outcomes. RESULTS: Median flexion contracture and median terminal flexion at presentation were 20 and 70°, respectively; at final follow-up, 59 of 60 patients (98%) had ≤10° flexion contracture and 49 of 60 patients (82%) had ≥90° of flexion. The 10-year survivorship free from reoperation for any reason, revision for any reason, and revision for aseptic loosening were 63, 87, and 97%, respectively. There were 27% percent of patients who underwent a manipulation under anesthesia postoperatively, which was the most common reason for return to the operating room. A greater number of prior surgeries was significantly associated with worse range of motion at the final follow-up (P = .004). There were no known radiation-associated complications. CONCLUSIONS: Patients with severe idiopathic arthrofibrosis following TKA treated with low-dose irradiation and RH revision maintained a gain in knee range of motion of 60° with reliable flexion contracture correction at a mean 6-year follow-up. A manipulation under anesthesia was common in the postoperative period. Survivorship free from revision for aseptic loosening was excellent at 10 years.

Shoulder Adhesive Capsulitis Prior to Total Knee Arthroplasty is Associated With Increased Rates of Postoperative Stiffness Requiring Manipulation Under Anesthesia and Arthroscopic Lysis of Adhesions.

BACKGROUND: Arthrofibrosis following total knee arthroplasty (TKA) and adhesive capsulitis (AC) of the shoulder develop via a similar pathologic process. The purpose of this study was to examine the relationship between these two conditions. METHODS: This was a retrospective cohort study using a large nationwide claims database. Patients who had a history of shoulder AC prior to TKA were compared to TKA patients who did not have AC history comparing rates of postoperative stiffness, manipulation under anesthesia (MUA), arthroscopic lysis of adhesions (LOAs), and revision arthroplasty at postoperative timepoints (3 months, 6 months, 1 year, and 2 years). RESULTS: Within 3 months, 6 months, 1 year, and 2 years of their TKAs, patients who had a history of AC prior to TKA were significantly more likely to experience stiffness (OR [odds ratio] = 1.29, 1.28, 1.32, and 1.36, respectively) and LOAs (OR = 6.78, 3.65, 2.99, and 2.81, respectively). They also showed increased risk of MUA within 6 months, 1 year, and 2 years (OR = 1.15, 1.15, and 1.16, respectively) of their TKAs. Patients having a preoperative diagnosis of AC did not have an increased risk of undergoing revision surgery 1 year or 2 years after their TKAs (P > .05). CONCLUSIONS: Patients diagnosed with AC prior to TKA experience higher rates of postoperative stiffness, resulting in additional interventions such as MUA and LOAs. These findings identify a particularly high-risk patient population that may benefit from additional interventions prior to and following TKA. LEVEL OF EVIDENCE: This is a level III prognostic study.

Patient-reported allergies are associated with increased rate of postoperative stiffness after arthroscopic rotator cuff repair.

BACKGROUND: Several risk factors have been identified for the development of postoperative shoulder stiffness, and there has been increasing interest in orthopedic literature regarding patient-reported allergy (PRA) as an identifiable risk factor for adverse outcomes. The purpose of this study is to determine whether PRAs are associated with subsequent rates of diagnosis of adhesive capsulitis (AC) or return to the operating room for postoperative shoulder stiffness within 2 years after arthroscopic rotator cuff repair (ARCR). METHODS: Current Procedural Terminology surgical billing codes were used to retrospectively identify patients who underwent ARCR at a single urban academic institution from January 2012 to December 2020 with minimum 2-year follow-up. Lysis of adhesions (LOA), manipulation under anesthesia (MUA), and AC of the shoulder were further queried within 2 years postoperatively for the ipsilateral shoulder. Patients were excluded if they had undergone ipsilateral MUA/LOA or received a diagnosis of AC before the index procedure. Demographic characteristics and medical comorbidities (hypertension, diabetes, hyperlipidemia, and hypothyroidism) were extracted from electronic medical records. Baseline characteristics were compared between patients with and without PRAs. Multivariate logistic regression analyses were performed to determine the association of the presence of PRAs overall, as well as the presence of 1, 2, or 3 or more PRAs, with subsequent MUA/LOA or diagnosis of AC within 2 years postoperatively. RESULTS: Of 7057 patients identified in the study period, 6583 were eligible for the final analysis. The mean age was 56.6 ± 11.7 years, and the mean body mass index was 29.1 ± 5.6. Overall, 19.3% of patients (n = 1271) reported at least 1 allergy, and 7.1% (n = 469) had >1 PRA. A total of 44 patients (0.7%) underwent subsequent ipsilateral MUA/LOA within 2 years postoperatively, whereas 93 patients (1.4%) received a diagnosis of ipsilateral AC in the same time frame. PRAs were significantly associated with subsequent diagnosis of AC (odds ratio [OR]: 2.39; 95% confidence interval [CI]: 1.45-3.92; P < .001), but not MUA/LOA (OR: 1.97, 95% CI: 1.26-3.61; P = .133). Patients with 2 PRAs had greater odds of being diagnosed with AC than patients with 1 PRA (OR: 2.74; 95% CI: 1.14-5.99; P = .012). Although this association was nonsignificant for MUA/LOA, patients with 2 PRAs (OR: 2.67; 95% CI: 0.96-8.80; P = .059) demonstrated a similar statistical trend. CONCLUSION: PRAs are associated with increased odds of receiving a diagnosis of AC within 2 years after ARCR but were not found to be associated with return to the operating room for postoperative stiffness.

Postoperative Angiotensin Receptor Blocker Use is Associated With Decreased Rates of Manipulation Under Anesthesia, Arthroscopic Lysis of Adhesions, and Prosthesis-Related Complications in Patients Undergoing Total Knee Arthroplasty.

BACKGROUND: The cellular mechanisms underlying excess scar tissue formation in arthrofibrosis following total knee arthroplasty (TKA) are well-described. Angiotensin receptor blockers (ARB), particularly losartan, is a commonly prescribed antihypertensive with demonstrated antifibrotic properties. This retrospective study aimed to assess the rates of 1- and 2-year postoperative complications in patients who filled prescriptions for ARBs during the 90 days after TKA. METHODS: Patients undergoing primary TKA were selected from a large national insurance database, and the impact of ARB use after TKA on complications was assessed. Of the 1,299,106 patients who underwent TKA, 82,065 had filled at least a 90-day prescription of losartan, valsartan, or olmesartan immediately following their TKA. The rates of manipulation under anesthesia (MUA), arthroscopic lysis of adhesions (LOA), aseptic loosening, periprosthetic fracture, and revision at 1 and 2 years following TKA were analyzed using multivariable logistic regressions to control for various comorbidities. RESULTS: ARB use was associated with decreased rates of MUA (odds ratio [OR] = 0.94, 95% confidence interval (CI), 0.90 to 0.99), arthroscopy/LOA (OR = 0.86, 95% CI, 0.77 to 0.95), aseptic loosening (OR = 0.71, 95% CI, 0.61 to 0.83), periprosthetic fracture (OR = 0.58, 95% CI, 0.46 to 0.71), and revision (OR = 0.79, 95% CI, 0.74 to 0.85) 2 years after TKA. CONCLUSIONS: ARB use throughout the 90 days after TKA is associated with a decreased risk of MUA, arthroscopy/LOA, aseptic loosening, periprosthetic fracture, and revision, demonstrating the potential protective abilities of ARBs. Prospective studies evaluating the use of ARBs in patients at risk for postoperative stiffness would be beneficial to further elucidate this association.

Unexpected positive cultures in patients with arthrofibrosis following total hip and total knee arthroplasty.

PURPOSE: It has been suggested that low-grade infections could be the cause of arthrofibrosis. However, this hypothesis has not been conclusively proven. The aim of this study is to assess the incidence of unexpected positive cultures (UPC) in patients undergoing revision total joint arthroplasty for a diagnosis of arthrofibrosis. METHODS: A retrospective single-centre review was performed. All patients who underwent an aseptic revision due to histologically confirmed arthrofibrosis (based on the synovial-like interface membrane (SLIM) criteria) were included. The incidence of UPC was then calculated. RESULTS: A total of 147 patients were included. Of these, 100 underwent a total knee arthroplasty (TKA) procedure and 46 a total hip arthroplasty (THA) surgery. One patient had a periprosthetic joint infection and was therefore excluded. Of the 146 included patients, 6 had confirmed UPC (4.08%). The following bacteria were identified: Anaerococcus octavius, Staphylococcus epidermidis, Enterobacter cloacae, Staphylococcus hominis, Streptococcus pluranimalium, Staphylococcus pettenkoferi. CONCLUSIONS: Our results suggest that the incidence of UPC in patients with arthrofibrosis is low. It is lower than that of UPC in patients that undergo a revision for other causes. There is no proven relationship between histologically confirmed arthrofibrosis following total joint arthroplasty and prosthetic joint infection.

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.

Evaluating the Efficacy of a Thermoresponsive Hydrogel for Delivering Anti-Collagen Antibodies to Reduce Posttraumatic Scarring in Orthopedic Tissues.

Excessive posttraumatic scarring in orthopedic tissues, such as joint capsules, ligaments, tendons, muscles, and peripheral nerves, presents a significant medical problem, resulting in pain, restricted joint mobility, and impaired musculoskeletal function. Current treatments for excessive scarring are often ineffective and require the surgical removal of fibrotic tissue, which can aggravate the problem. The primary component of orthopedic scars is collagen I-rich fibrils. Our research team has developed a monoclonal anti-collagen antibody (ACA) that alleviates posttraumatic scarring by inhibiting collagen fibril formation. We previously established the safety and efficacy of ACA in a rabbit-based arthrofibrosis model. In this study, we evaluate the utility of a well-characterized thermoresponsive hydrogel (THG) as a delivery vehicle for ACA to injury sites. Crucial components of the hydrogel included N-isopropylacrylamide, poly(ethylene glycol) diacrylate, and hyaluronic acid. Our investigation focused on in vitro ACA release kinetics, stability, and activity. Additionally, we examined the antigen-binding characteristics of ACA post-release from the THG in an in vivo context. Our preliminary findings suggest that the THG construct exhibits promise as a delivery platform for antibody-based therapeutics to reduce excessive scarring in orthopedic tissues.

Adhesions in the setting of hip arthroscopy.

With the growing number of primary arthroscopies performed, patients requiring revision hip arthroscopies for various issues is high including postoperative adhesion formation, a source of pain, mechanical symptoms, range of motion limitation, stiffness, and microinstability. Adhesions are a consequence of biological pathways that have been stimulated by injury or surgical interventions leading to an increased healing response. Preventative efforts have included surgical adjuncts during/after primary hip arthroscopy, biologic augmentation, and postoperative rehabilitation. Treatment options for adhesion formation includes surgical lysis of adhesions with or without placement of biologic membranes aimed at inhibiting adhesion reformation as well as systemic medications to further reduce the risk. Postoperative rehabilitation exercises have also been demonstrated to prevent adhesions as a result of hip arthroscopy. Ongoing clinical trials are further investigating pathways and prevention of adhesion formation.

Polyethylene exchange versus full component revision for arthrofibrosis following total knee arthroplasty: A retrospective cohort analysis.

Introduction: Arthrofibrosis occurs in up to 10% of patients who undergo total knee arthroplasty (TKA). For cases that are not amenable to manipulation under anesthesia (MUA), there is little consensus on how many components should be revised. We compared outcomes of polyethylene exchanges, when doing lysis of adhesions (LOA) versus full component revision. Specifically, we assessed: (1) re-operation rates at one and two years; (2) rates of surgical complications at one year; and (3) associated risk factors for requiring a LOA. Methods: A database queried all patients who underwent revision TKA for arthrofibrosis. A total of 2410 patients were identified, 1120 (46.5%) of which underwent all-component knee revision, while the remaining 1290 (53.5%) underwent polyethylene spacer revision. Multivariate logistic regressions assessed re-operation rates and risk factors for requiring LOA. Results: The incidence and odds of re-operation within one year following polyethylene exchange was not significantly different than full component revision (10.9 versus 12.9%, odds ratio (OR) 0.83, 95% confidence interval (CI) [0.64-1.06], p = 0.145). However, the adjusted models for re-operation within one- and two-years following LOA in the form of polyethylene exchange revision was significantly higher than the full component revision cohort (OR 1.52 CI [1.07-2.17], p = 0.022 and OR 1.44 CI [1.06-1.97] p = 0.022). Risk factors associated with the need for lysis of adhesions included age less than 60 years, depression, fibromyalgia, and anxiety. Conclusions: Full component revision TKA for arthrofibrosis was associated with lower two-year re-operation rate than polyethylene exchange. Risk factors for LOA include younger age and fibromyalgia.

Targeting CD44 Receptor Pathways in Degenerative Joint Diseases: Involvement of Proteoglycan-4 (PRG4).

Rheumatoid arthritis (RA), osteoarthritis (OA), and gout are the most prevalent degenerative joint diseases (DJDs). The pathogenesis underlying joint disease in DJDs remains unclear. Considering the severe toxicities reported with anti-inflammatory and disease-modifying agents, there is a clear need to develop new treatments that are specific in their effect while not being associated with significant toxicities. A key feature in the development of joint disease is the overexpression of adhesion molecules, e.g., CD44. Expression of CD44 and its variants in the synovial tissues of patients with DJDs is strongly associated with cartilage damage and appears to be a predicting factor of synovial inflammation in DJDs. Targeting CD44 and its downstream signaling proteins has emerged as a promising therapeutic strategy. PRG4 is a mucinous glycoprotein that binds to the CD44 receptor and is physiologically involved in joint lubrication. PRG4-CD44 is a pivotal regulator of synovial lining cell hemostasis in the joint, where lack of PRG4 expression triggers chronic inflammation and fibrosis, driven by persistent activation of synovial cells. In view of the significance of CD44 in DJD pathogenesis and the potential biological role for PRG4, this review aims to summarize the involvement of PRG4-CD44 signaling in controlling synovitis, synovial hypertrophy, and tissue fibrosis in DJDs.

Risk factors for failure of manipulation under anesthesia in posttraumatic knee stiffness.

OBJECTIVES: To determine the proportion of patients who fail manipulation under anesthesia (MUA) as a treatment for posttraumatic knee stiffness and determine the risk factors for MUA failure. METHODS: A retrospective cohort study was performed at a level I trauma center. We identified 213 knees in 199 patients with arthrofibrosis treated by MUA within 1 year of injury from 2007 to 2020. The primary outcome was MUA failure as defined by need for repeat MUA or surgical release after MUA. Multivariable logistic regression was used to determine the association between MUA failure and potential risk factors. RESULTS: Overall, 111 knees (52%) failed treatment with MUA. An association was demonstrated between MUA failure and delay in treatment >90 days after injury (OR 3.6, p < 0.01), neurologic injury (OR 2.2, p = 0.02), and pre-procedure knee flexion <45° (OR 1.9, p < 0.01). The rate of failure for knees with no risk factors was 0% (0 of 14), 37% for knees with one risk factor (27 of 73), and 67% (84 of 126) for knees with two or more risk factors. CONCLUSION: For patients whose MUA is delayed beyond 90 days postinjury, pre-manipulation knee flexion is <45°, or those with associated neurologic injury; odds of MUA failing to correct posttraumatic arthrofibrosis are significantly increased. The likelihood of obtaining adequate range of motion (ROM) with MUA alone is lower than reported in other populations, with a higher likelihood of being treated with surgical release or additional MUA to attempt to obtain adequate ROM.

Manipulation Under Anesthesia and/or Lysis of Adhesions After Anterior Cruciate Ligament Reconstruction in Female Basketball Players: Does Race Play a Role?

BACKGROUND: Arthrofibrosis can limit function and return to sport after anterior cruciate ligament (ACL) reconstruction. Previously reported risk factors for developing arthrofibrosis after ACL reconstruction include female sex, age <18 years, time from injury to surgery <28 days, concomitant meniscal repair, prolonged immobilization, and genetic factors. There is a lack of evidence regarding whether race plays a significant role. HYPOTHESIS: The risk of undergoing manipulation under anesthesia (MUA) and/or lysis of adhesions (LOA) after primary ACL reconstruction with bone-patellar tendon-bone (BTB) autograft in female basketball players is higher in African American players than in White players. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Using a computerized relational database, the authors identified competitive female basketball players who underwent primary ACL reconstruction with BTB autograft by the senior author over a 13-year period. Data previously entered from examinations and surgical findings were reviewed retrospectively. Univariate statistics and multivariable logistic regression were used to assess the relationship between undergoing subsequent MUA and/or LOA and study predictors. RESULTS: A total of 186 knees (114 African American knees and 72 White knees) met inclusion criteria. The overall rate of MUA and/or LOA was 8.6%. Thirteen African American knees (11.4%) and 3 White knees (4.2%) underwent MUA and/or LOA for treatment of arthrofibrosis. No study predictor was found to have a statistically significant relationship with the rate of MUA and/or LOA on univariate analysis. However, when controlling for body mass index and previously described risk factors (age <18 years, time from injury to surgery ≤28 days, and concomitant meniscal repair) in the logistic regression model, the authors found that MUA and/or LOA was more likely in African American (odds ratio, 4.01 [95% CI, 1.01-15.92]; P = .049) than in White female players and in patients who underwent ACL reconstruction within 28 days of injury (odds ratio, 4.01 [95% CI, 1.18-13.57]; P = .026) compared with those with surgery delayed beyond 28 days. CONCLUSION: In female basketball players, the present study found a statistically significantly increased risk for undergoing MUA and/or LOA after primary ACL reconstruction with BTB autograft in African American females compared with White females and in patients who underwent ACL reconstruction within 28 days of injury.