Biologic Impact of Anterior Cruciate Ligament Injury and Reconstruction.

Surgical intervention after anterior cruciate ligament (ACL) tears is typically required because of the limited healing capacity of the ACL. However, mechanical factors and the inflammatory response triggered by the injury and surgery can impact patient outcomes. This review explores key aspects of ACL injury and reconstruction biology, including the inflammatory response, limited spontaneous healing, secondary inflammation after reconstruction, and graft healing processes. Understanding these biologic mechanisms is crucial for developing new treatment strategies and enhancing patient well-being. By shedding light on these aspects, clinicians and researchers can work toward improving quality of life for individuals affected by ACL tears.

Hyperbaric oxygen therapy enhances graft healing and mechanical properties after anterior cruciate ligament reconstruction: An experimental study in rabbits.

Hyperbaric oxygen therapy (HBOT) has proven successful in wound healing. However, its potential effects on anterior cruciate ligament (ACL) injuries remain uncertain. This study aimed to investigate the impact of HBOT on graft healing following ACL reconstruction in rabbits. Male New Zealand rabbits underwent ACL reconstruction and were randomly divided into two groups: the HBOT group and the ambient air group. The HBOT group received 100% oxygen at 2.5 atmospheres absolute for 2 h daily for 5 consecutive days, starting from the first day after surgery. The ambient air group was maintained in normal room air throughout the entire period. After 12 weeks following the surgery, animals were euthanized, and their knees were harvested for analysis. The HBOT group demonstrated superior graft maturation and integration in comparison to the ambient air group, as evidenced by lower graft signal intensity on magnetic resonance imaging, decreased femoral and tibial tunnel size, and higher bone mineral density values on high-resolution peripheral quantitative computed tomography scans. Additionally, biomechanical testing indicated that the HBOT group had greater load to failure and stiffness values than the ambient air group. In conclusion, the adjuvant use of HBOT improved ACL graft maturation and integration, reduced tunnel widening, and enhanced the biomechanical properties of the graft. These results may provide important insights into the potential clinical application of HBOT as a therapeutic intervention to enhance graft healing after ACL reconstruction, paving the way for further research in this area.

Increased risk of reoperation and failure to attain clinically relevant improvement following autologous chondrocyte implantation of the knee in female patients and individuals with previous surgeries: a time-to-event analysis based on the German cartilage registry (KnorpelRegister DGOU).

PURPOSE: This study aimed to analyze the risk of reoperation following autologous chondrocyte implantation (ACI) of the knee utilizing third-generation ACI products in a time-to-event analysis and report on the associated patient-reported outcome measures (PROM) in case of reoperation. METHODS: Patients undergoing ACI were included from a longitudinal database. Patient age, sex, body mass index (BMI), number of previous surgeries, lesion localization, lesion size, symptom duration, as well as time and type of reoperation was extracted. A cox proportional-hazards model was applied to investigate the influence of baseline variables on risk of reoperation. Reoperation was defined as any type of subsequent ipsilateral knee surgery, excluding hardware removal. The Knee Injury and Osteoarthritis Outcome Score (KOOS) was utilized to compare PROM between patients with and without reoperation. RESULTS: A total of 2039 patients were included with 1359 (66.7%) having a minimum follow-up of 24 months. There were overall 243 reoperations (prevalence 17.9%). Minor arthroscopic procedures (n = 96, 39.5%) and revision cartilage repair procedures (n = 78, 32.1%) were the most common reoperations. Nineteen patients (0.9%) reported conversion arthroplasty at 17.7 (10.4) months after ACI. Female sex (HR 1.5, 95% CI [1.2, 2.0], p = 0.002) and the presence of 1-2 previous surgeries (HR 1.5, 95% CI [1.1, 2.0], p = 0.010), or more than 2 previous surgeries (HR 1.9, 95% CI [1.2, 2.9], p = 0.004) were significantly associated with increased risk of reoperation following ACI. Significantly less patients surpassed the minimal clinically important difference (MCID) in the reoperation group at 24 months regarding the KOOS subscores pain (OR 1.6, 95% CI [1.1, 2.2]), quality of life (OR 2.2, 95% CI [1.6, 3.2]), symptoms (OR 2.0 [1.4, 2.9]), and sports (OR 2.0 [1.4, 2.8]). CONCLUSION: Female patients and individuals with a history of previous surgeries face an elevated risk of requiring reoperation after undergoing ACI, which is associated with failure to attain clinically relevant improvements. A thorough evaluation of the indications for ACI is paramount, particularly when patients have a history of previous surgeries. LEVEL OF EVIDENCE: Level III.

Effect of Tibiofemoral Rotation Angle on Graft Failure After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Coronal and sagittal malalignment of the knee are well-recognized risk factors for failure after anterior cruciate ligament (ACL) reconstruction (ACLR). However, the effect of axial malalignment on graft survival after ACLR is yet to be determined. PURPOSE: To evaluate whether increased tibiofemoral rotational malalignment, namely, tibiofemoral rotation angle (TFA) and tibial tubercle-trochlear groove (TT-TG) distance, is associated with graft failure after ACLR. STUDY DESIGN: Cohort study; Level of evidence, 3. METHODS: In this retrospective matched control study of a single center's database, 151 patients who underwent revision ACLR because of graft failure (ACLR failure group, defined as symptomatic patients with anterior knee instability and an ACL graft tear appreciated on magnetic resonance imaging [MRI] and confirmed during arthroscopic surgery) were compared with a matched control group of 151 patients who underwent primary ACLR with no evidence of failure after ≥2-year follow-up (intact ACLR group). Patients were matched by sex, age, and meniscal injury during primary ACLR. Axial malalignment was assessed on preoperative MRI through the TFA and the TT-TG distance. Sagittal alignment was measured through the posterior tibial slope on MRI. The optimal TFA cutoff associated with graft failure was identified by a receiver operating characteristic curve. The Kaplan-Meier curve with log-rank analysis was performed to evaluate the influence of the TFA on ACLR longevity. RESULTS: The mean age was 25.7 ± 10.4 years for the ACLR failure group and 25.9 ± 10.0 years for the intact ACLR group. Among all the included patients, 174 (57.6%) were male. In the ACLR failure group, the mean TFA was 5.8°± 4.5° (range, -5° to 16°), while it was 3.0°± 3.3° (range, -3° to 15°) in the intact ACLR group (P < .001). Neither the TT-TG distance nor the posterior tibial slope presented statistical differences between the groups. The receiver operating characteristic curve suggested an optimal TFA cutoff of 4.5° for graft failure (area under the curve = 0.71; P < .001; sensitivity, 68.2%; specificity, 75.5%). Considering this a threshold, patients who had a TFA ≥4.5° had 6.6 times higher odds of graft failure compared with patients with a TFA <4.5° (P < .001). Survival analysis demonstrated a 5-year survival rate of 81% in patients with a TFA <4.5°, while it was 44% in those with a TFA ≥4.5° (P < .001). CONCLUSION: An increased TFA was associated with increased odds of ACLR failure when the TFA was ≥4.5°. Measuring the TFA in patients with ACL tears undergoing reconstruction may inform the surgeon about additional factors that may require consideration before ACLR for a successful outcome.

Synovial Fluid Inflammatory Profiles did not Differ between Isolated Anterior Cruciate Ligament and Multi-ligament Knee Injuries.

Objective and design: The purpose of this study was to compare synovial concentrations of pro- and anti-inflammatory cytokines between multiple-ligament knee injured (MLKI) and anterior cruciate ligament (ACL)-injured patients. Subjects: 14 patients with MLKI and 10 patients with isolated ACL injury. Methods: Synovial fluid was aspirated from the operative knee at the time of surgery and the concentrations of pro- and anti-inflammatory markers in the synovial fluid were determined. Structures injured, the time between injury and surgery, and demographic factors were collected. Linear regressions were used to determine the association between injury pattern and synovial inflammatory markers when controlling for age, BMI, and time between injury and surgery. Results: When adjusting for group differences in age, BMI and the time between injury and surgery, no group differences were detected (interferon gamma (p = 0.11), interleukin-1beta (IL-1b, p = 0.35), IL-2 (p = 0.28), IL-4 (p = 0.64), IL-6 (p = 0.37), IL-8 (p = 0.54), IL-10 (p = 0.25), IL-12p70 (p = 0.81), IL-13 (p = 0.31), and tumor necrosis factor-alpha (p = 0.90)). Conclusion: Synovial fluid inflammatory markers did not differ between MLKI and isolated ACL injuries. MLKIs have a greater prevalence of postoperative arthrofibrosis when compared to isolated ACL injuries; however, this may be due in part to factors other than the inflammatory status of the joint.

Human synovial fluid interleukin-6, but not type II collagen breakdown, positively correlated with pain after anterior cruciate ligament injury and reconstruction.

Anterior cruciate ligament (ACL) injury initiates a biochemical cascade thought to contribute to the onset and progression of posttraumatic osteoarthritis (PTOA). Interleukin-1ß (IL-1ß), IL-6, and C-telopeptide fragments of type II collagen (CTX-II) are implicated in joint inflammation and cartilage degradation following ACL injury; however, their association with pain is still being explored. The purpose of this study was to evaluate the associations between synovial fluid concentrations of IL-1ß, IL-6, and CTX-II with pain following ACL injury and reconstruction. We hypothesized that greater IL-1ß, IL-6, and CTX-II would correlate with greater Pain Visual Analogue Scale (VAS) scores. This was a secondary analysis of 23 patients (mean age = 18.4 years, BMI = 27.4, 13 females/10 males) with acute ACL tears who participated in a pilot randomized trial. Synovial fluid and VAS scores were collected on the day of initial presentation, at ACL reconstruction, and 1 and 4 weeks after surgery. Synovial fluid concentrations of IL-1ß, IL-6, and CTX-II were assessed using enzyme-linked immunoabsorbent assays, and repeated measures correlations were used to assess the relationships between pain and synovial IL-1ß, IL-6, or CTX-II after ACL injury and reconstruction. Pain was positively correlated with synovial fluid IL-6 concentrations (r = 0.52, p < 0.001); however, pain was inversely correlated with CTX-II (r = -0.39, p = 0.002). IL-1ß had no significant correlation with pain. Statement of clinical relevance: PTOA has been described as a "silent killer" and these results suggest that early PTOA may have pro-inflammatory pathways that are not primarily associated with pain but still lead to progressive cartilage loss.

Systematic Review of Clinical Results After Medial Meniscus Allograft Transplantation Reveals Improved Patient Reported Outcomes at Greater Than 5 Years Follow-Up.

PURPOSE: To systematically summarize the medial meniscus allograft transplantation (MAT) reported outcomes and evaluate whether the surgical technique is associated with allograft extrusion and knee function. METHODS: Systematic review was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Inclusion criteria were English-language clinical studies involving arthroscopically assisted medial MAT that reported the surgical technique and the presence of graft extrusion or functional outcomes after surgery. Studies in which outcomes for medial MAT could not be separated from lateral MAT were excluded. Surgical technique, allograft-related characteristics, and clinical outcomes were extracted. RESULTS: Twenty-four studies with 328 medial MAT were included, 58.3% studies qualified as level 4 of evidence, 29.2% as level 3, and 12.5% as level 2. Allograft fixation techniques were bone plug (235/328 [71.6%]), bone bridge/trough (55/328 [16.8%]), and soft-tissue suture fixation only (38/328 [11.6%]). Relative percentage of extrusion after surgery ranged from 24.8% to 53.7%. Major extrusion (>3 mm) ranged from zero to 78%. Overall, functional scores improved after medial MAT. None of surgical techniques were associated with poor functional outcomes or extruded meniscus; however, nonanatomical placement of the anterior and posterior horns appeared to increase meniscus extrusion. CONCLUSION: Medial MAT provides favorable outcomes, with acceptable rates of complication and failure regardless of surgical technique. Although allograft extrusion appears equivalent for both bone plug and soft-tissue fixation techniques, positioning allograft horns at the native meniscal footprint may be critical for preventing extrusion. However, the heterogeneity and low level of evidence of the studies included in this review prevent decisive conclusions regarding optimal MAT fixation techniques, clinical significance of allograft extrusion, or comparative clinical outcomes after medial MAT. LEVEL OF EVIDENCE: Level IV - systematic review of Level II to IV studies.

Pain Early After Anterior Cruciate Ligament Reconstruction is Associated With 6-Month Loading Mechanics During Running.

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) results in persistent altered knee biomechanics, but contributing factors such as pain or patient function, leading to the altered loading, are unknown. HYPOTHESIS: Individuals with worse self-reported pain after ACLR would have poorer biomechanics during running, and poor loading mechanics would be present in the ACLR limb compared with contralateral and control limbs. STUDY DESIGN: Cohort pilot study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 20 patients after ACLR (age, 18.4 ± 2.7 years; height, 1.7 ± 0.1 m; mass, 84.2 ± 19.4 kg) completed visual analog scale and Knee Injury and Osteoarthritis Outcomes Score (KOOS) at 1 and 6 months postsurgery. At 6 months postsurgery, patients underwent biomechanical testing during running. A total of 20 control individuals also completed running biomechanical analyses. Associations between patient outcomes and biomechanics were conducted, and differences in running biomechanics between groups were analyzed. RESULTS: KOOS pain score 1 month after surgery was associated with peak ACLR knee abduction moment (R2 = 0.35;P = 0.01). At 6-months, KOOS sport score was related to peak abduction moment in the ACLR limb (R2 = 0.23; P = 0.05). For change scores, the improvement in pain scores related to ACLR limb peak knee abduction moment (R2 = 0.55; P = 0.001). The ACLR limb had lower knee excursion, extension moments, and ground-reaction forces compared with the uninvolved and control limb. The uninvolved limb also had higher ground-reaction forces compared with the ACLR limb and control limb. CONCLUSION: These results suggest that patient-reported outcomes 1 and 6 months after surgery are associated with running mechanics 6 months after ACLR. Further, the underloading present in the ACLR limb and overloading in the uninvolved limb indicates greater need for running rehabilitation after ACLR. CLINICAL RELEVANCE: Understanding pain and how it may be linked to movement dysfunction is important for improving long-term outcomes.

Complement system dysregulation in synovial fluid from patients with persistent inflammation following anterior cruciate ligament reconstruction surgery.

Introduction: Patients with anterior cruciate ligament injury are at high risk of posttraumatic osteoarthritis and their response to reconstructive surgery and rehabilitation vary. Proteins identified in the orchestration of the acute inflammatory response may be predictive of patient outcomes. Objective: An unbiased, bottom-up proteomics approach was used to discover novel targets for therapeutics in relation to dysregulation in the orchestration of inflammatory pathways implicated in persistent joint inflammation subsequent to joint trauma. Methods: Synovial fluid was aspirated from patients at 1 week and 4 weeks after anterior cruciate ligament reconstruction (ACLR) and interleukin 6 (IL-6) concentrations were quantified by enzyme-linked immunosorbent assay. Patients were segregated into IL-6low and IL-6high groups based on IL-6 concentrations in synovial fluid at 4-weeks postoperation and proteins in synovial fluid were analyzed using qualitative, bottom-up proteomics. Abundance ratios were calculated for IL-6high and IL-6low groups as 4 weeks postoperation:1 week postoperation. Results: A total of 291 proteins were detected in synovial fluid, 34 of which were significantly (P < .05) differentially regulated between groups. Proteins associated with the classical and alternative complement cascade pathways were increased in the IL-6high compared to IL-6low group. Insulin-like growth factor-binding protein 6 (IGFBP-6) was increased by nearly 60-fold in the IL-6low group. Conclusions: Patients segregated by IL-6 concentration in synovial fluid at 4 weeks post-ACLR demonstrated differential regulation of multiple pathways, providing opportunities to investigate novel targets, such as IGFBP-6, and to take advantage of therapeutics already approved for clinical use in other diseases that target inflammatory pathways, including the complement system.

Treatment of post-meniscectomy knee symptoms with medial meniscus replacement results in greater pain reduction and functional improvement than non-surgical care.

PURPOSE: Partial meniscectomy is a common orthopedic procedure intended to improve knee pain and function in patients with irreparable meniscal tears. However, 6-25% of partial meniscectomy patients experience persistent knee pain after surgery. In this randomized controlled trial (RCT) involving subjects with knee pain following partial meniscectomy, it was hypothesized that treatment with a synthetic medial meniscus replacement (MMR) implant provides significantly greater improvements in knee pain and function compared to non-surgical care alone. METHODS: In this prospective, multicenter RCT, subjects with persistent knee pain following one or more previous partial meniscectomies were randomized to receive either MMR or non-surgical care. This analysis evaluated the 1-year outcomes of this 2-year clinical trial. Patient-reported knee pain, function, and quality of life were measured using nine separate patient-reported outcomes. The primary outcomes were the pain subscale of the Knee injury and Osteoarthritis Outcome Score (KOOS) and the average of all five KOOS subscales (KOOS Overall). Treatment cessation was defined as permanent device removal in the MMR group and any surgical procedure to the index knee in the non-surgical care group. RESULTS: Treated subjects had a median age of 52 years old (range 30-69 years) and one or more previous partial meniscectomies at a median of 34 months (range 5-430 months) before trial entry. Among 127 subjects treated with either MMR (n = 61) or non-surgical care (n = 66), 11 withdrew from the trial or were lost to follow-up (MMR, n = 0; non-surgical care, n = 11). The magnitude of improvement from baseline to 1 year was significantly greater in subjects who received MMR in both primary outcomes of KOOS Pain (P = 0.013) and KOOS Overall (P = 0.027). Treatment cessation was reported in 14.5% of non-surgical care subjects and only 4.9% of MMR subjects (n.s.). CONCLUSION: Treatment with the synthetic MMR implant resulted in significantly greater improvements in knee pain, function, and quality of life at 1 year of follow-up compared to treatment with non-surgical care alone. LEVEL OF EVIDENCE: I.

Knee registries: state of the art.

Sports injuries, trauma and the globally ageing and obese population require increasing levels of knee surgery. Shared decision making has replaced the paternalistic approach to patient management. Evidence-based medicine underpins surgical treatment strategies, from consenting an individual patient to national healthcare system design. The evolution of successful knee-related registries starting from specific arthroplasty registries has given rise to ligament reconstruction, osteotomy and cartilage surgery registries developing as platforms for surgical outcome data collection. Stakeholders include surgeons and their patients, researchers, healthcare systems, as well as the funding insurers and governments. Lately, implant manufacturers have also been mandated to perform postmarket surveillance with some hoping to base that on registry data. Aiming to assess the current status of knee-related registries, we performed a comprehensive literature and web search, which yielded 23 arthroplasty, 8 ligament, 4 osteotomy and 3 articular cartilage registries. Registries were evaluated for their scope, measured variables, impact and limitations. Registries have many advantages as they aim to increase awareness of outcomes; identify trends in practice over time, early failing implants, outlier surgeon or institution performance; and assist postmarketing surveillance. International collaborations have highlighted variations in practice. The limitations of registries are discussed in detail. Inconsistencies are found in collected data and measured variables. Potential measurement and selection biases are outlined. Without mandated data collection and with apparent issues such as unverified patient reporting of complications, registries are not designed to replace adverse event recording in place of a proper safety and efficacy study, as demanded by regulators. Registry 'big data' can provide evidence of associations of problems. However, registries cannot provide evidence of causation. Hence, without careful consideration of the data and its limitations, registry data are at risk of incorrectly drawn conclusions and the potential of misuse of the results. That must be guarded against. Looking at the future, registry operators benefit from a collective experience of running registries as they mature, allowing for improvements across specialties. Large-scale registries are not only of merit, improving with stakeholder acceptance, but also are critical in furthering our understanding of our patients' outcomes. In doing so, they are a critical element for our future scientific discourse.

The Relationship Between Patient Expectations and Functional Outcomes in Patients Undergoing Cartilage Repair of the Knee: A Mixed Methods Study.

CONTEXT: Patient expectations have been shown to be a major predictor of outcomes. Fulfilled expectations have been linked to increased patient satisfaction and rehabilitation adherence. Expectations may be influenced by a variety of factors, including patient characteristics, preoperative function, or disease characteristics. It is currently unknown what factors may influence patient expectations prior to cartilage repair of the knee, and to what degree. Furthermore, understanding the importance and values of those expectations for recovery using mixed methods has not previously been conducted in this patient population. The purpose of this mixed methods study is to examine and explore the relationships between patient expectations and functional outcome in patients undergoing cartilage repair of the knee. DESIGN: A mixed methods design was used. METHODS: Twenty-one patients scheduled to undergo cartilage repair of the knee were included. Participants completed the Hospital for Special Surgery Knee Surgery Expectations Survey and the Knee Injury and Osteoarthritis Outcome Score at their preoperative visit. Knee Injury and Osteoarthritis Outcome Scores were also obtained at 3 and 6 months postsurgery. A selected sample of 6 participants participated in semi-structured interviews 6 months postsurgery. Pearson correlation coefficients were used to determine relationships between expectations and functional outcome. RESULTS: Patients have moderate expectations for recovery, and these expectations were positively associated with preoperative pain, activities of daily living, and quality of life. Expectations also correlated with symptoms 3 months postsurgery, but there were no other significant correlations between preoperative expectations and postoperative function in the short term. Four qualitative themes emerged as participants described how previous recovery experiences shaped their expectations. CONCLUSIONS: Formalized patient and caregiver education, prehabilitation, and the use of psychological skills during rehabilitation may help to manage patient expectations and provide more focused and individualized care, thus improving outcomes.

Algorithm for Treatment of Focal Cartilage Defects of the Knee: Classic and New Procedures.

OBJECTIVE: To create a treatment algorithm for focal grade 3 or 4 cartilage defects of the knee using both classic and novel cartilage restoration techniques. DESIGN: A comprehensive review of the literature was performed highlighting classic as well as novel cartilage restoration techniques supported by clinical and/or basic science research and currently being employed by orthopedic surgeons. RESULTS: There is a high level of evidence to support the treatment of small to medium size lesions (<2-4 cm2) without subchondral bone involvement with traditional techniques such as marrow stimulation, osteochondral autograft transplant (OAT), or osteochondral allograft transplant (OCA). Newer techniques such as autologous matrix-induced chondrogenesis and bone marrow aspirate concentrate implantation have also been shown to be effective in select studies. If subchondral bone loss is present OAT or OCA should be performed. For large lesions (>4 cm2), OCA or matrix autologous chondrocyte implantation (MACI) may be performed. OCA is preferred over MACI in the setting of subchondral bone involvement while cell-based modalities such as MACI or particulated juvenile allograft cartilage are preferred in the patellofemoral joint. CONCLUSIONS: Numerous techniques exist for the orthopedic surgeon treating focal cartilage defects of the knee. Treatment strategies should be based on lesion size, lesion location, subchondral bone involvement, and the level of evidence supporting each technique in the literature.

Safety and Efficacy of an Amniotic Suspension Allograft Injection Over 12 Months in a Single-Blinded, Randomized Controlled Trial for Symptomatic Osteoarthritis of the Knee.

PURPOSE: The purpose of this study is to determine the efficacy of amniotic suspension allograft (ASA) compared to hyaluronic acid (HA) and saline at up to 12 months of follow-up through the use of patient-reported outcomes, immunoglobulin levels, and anti-human leukocyte antigen (HLA) levels. METHODS: Within this multicenter study, 200 patients were randomized 1:1:1 to a single intra-articular injection of saline, HA, or ASA. Patient-reported outcomes, including Knee Injury and Osteoarthritis Outcome Score (KOOS) and visual analog scale (VAS) score, were collected at multiple time points (baseline, 1 week, 6 weeks, 3 months, 6 months) out to 12 months to assess improvements in pain and function. Radiographs at baseline and 12 months were taken to determine radiographic changes, while blood was collected at baseline, 6 weeks, and 6 months to determine changes in immunoglobulins and anti-HLA levels. Statistical analyses were performed using last observation carried forward and mixed effects model for repeated measures. RESULTS: Treatment with ASA resulted in significant improvements in KOOS and VAS scores that were maintained through 12 months (P < .05). Treatment with ASA resulted in a 63.2% responder rate at 12 months using the Outcome Measures in Arthritis Clinical Trials-Osteoarthritis Research Society International simplified definition. There were no significant differences between groups for radiographic measures in the index knee, immunoglobulins, C-reactive protein, or anti-HLA serum levels (P > .05). The number and type of adverse events (AEs) reported for ASA were comparable to the HA injection group, while no treatment-emergent AEs were reported for the saline group. CONCLUSIONS: This randomized controlled trial of ASA vs HA and saline for the treatment of symptomatic knee osteoarthritis demonstrated clinically meaningful improved outcomes with ASA over the controls out to 12 months postinjection. No concerning immunologic or adverse reactions to the ASA injection were identified with regards to severe AEs, immunoglobulin, or anti-HLA levels. LEVEL OF EVIDENCE: Level I, randomized controlled multicenter trial.

Cartilage Disease of the Patellofemoral Joint: Realignment, Restoration, Replacement.

Chondral lesions of the patellofemoral joint are common, and when symptomatic they can be difficult to manage. Not only are there various degrees of injury with multiple etiologies, but patellofemoral anatomy is complex and the patient's lower extremity alignment may contribute to the pathology. Treatment depends on the location, size, and depth of the lesion and may require realignment or concomitant stabilizing procedures. Tibial tubercle osteotomy can be performed in isolation or combined with various cartilage-based treatments, including marrow stimulation techniques, autologous chondrocyte implantation, osteochondral autograft, and osteochondral allograft. End-stage lesions, failed primary patellofemoral cartilage restoration with diffuse involvement, or isolated primary patellofemoral arthritis may be amenable to treatment with patellofemoral arthroplasty. Recent investigations in properly indicated patients using advanced techniques have shown that management of patellofemoral cartilage disease is now more effective and predictable than in the past.

A Comparison of Neuromuscular Electrical Stimulation Parameters for Postoperative Quadriceps Strength in Patients After Knee Surgery: A Systematic Review.

CONTEXT: Postoperative quadriceps strength weakness after knee surgery is a persistent issue patients and health care providers encounter. OBJECTIVE: To investigate the effect of neuromuscular electrical stimulation (NMES) parameters on quadriceps strength after knee surgery. DATA SOURCES: CINAHL, MEDLINE, SPORTDiscus, and PubMed were systematically searched in December 2018. STUDY SELECTION: Studies were excluded if they did not assess quadriceps strength or if they failed to report the NMES parameters or quadriceps strength values. Additionally, studies that applied NMES to numerous muscle groups or simultaneously with other modalities/treatments were excluded. Study quality was assessed with the Physiotherapy Evidence Database (PEDro) scale for randomized controlled trials. STUDY DESIGN: Systematic review. LEVEL OF EVIDENCE: Level 1. DATA EXTRACTION: Treatment parameters for each NMES treatment was extracted for comparison. Quadriceps strength means and standard deviations were extracted and utilized to calculate Hedge g effect sizes with 95% CIs. RESULTS: Eight RCTs were included with an average Physiotherapy Evidence Database scale score of 5 ± 2. Hedge g effect sizes ranged from small (-0.37; 95% CI, -1.00 to 0.25) to large (1.13; 95% CI, 0.49 to 1.77). Based on the Strength of Recommendation Taxonomy Quality of Evidence table, the majority of the studies included were low quality RCTs categorized as level 2: limited quality patient-oriented evidence. CONCLUSION: Because of inconsistent evidence among studies, grade B evidence exists to support the use of NMES to aid in the recovery of quadriceps strength after knee surgery. Based on the parameters utilized by studies demonstrating optimal treatment effects, it is recommended to implement NMES treatment during the first 2 postoperative weeks at a frequency of ≥50 Hz, at maximum tolerable intensity, with a biphasic current, with large electrodes and a duty cycle ratio of 1:2 to 1:3 (2- to 3-second ramp).

Anterior cruciate ligament reconstruction reinitiates an inflammatory and chondrodegenerative process in the knee joint.

Anterior cruciate ligament (ACL) injury leads to a sustained increase in synovial fluid concentrations of inflammatory cytokines and biomarkers of cartilage breakdown. While this has been documented post-injury, it remains unclear whether ACL reconstruction surgery contributes to the inflammatory process and/or cartilage breakdown. This study is a secondary analysis of 14 patients (nine males/five females, mean age = 9, mean BMI = 28) enrolled in an IRB-approved randomized clinical trial. Arthrocentesis was performed at initial presentation (mean = 6 days post-injury), immediately prior to surgery (mean = 23 days post-injury), 1-week post-surgery, and 1-month post-surgery. Enzyme-linked immunosorbant assay kits were used to determine concentrations of carboxy-terminal telopeptides of type II collagen (CTXII), interleukin-6 (IL-6), and IL-1ß in the synovial fluid. The log-transformed IL-1ß was not normally distributed; therefore, changes between time points were evaluated using a non-parametric Kruskal-Wallis one-way ANOVA. IL-1ß concentrations significantly increased from the day of surgery to the first postoperative time point (P ≤ .001) and significantly decreased at the 4-week postoperative visit (P = .03). IL-1ß concentrations at the 4-week postoperative visit remained significantly greater than both preoperative time points (P > .05). IL-6 concentrations at 1-week post-surgery were significantly higher than at initial presentation (P = .013), the day of surgery (P < .001), and 4 weeks after surgery (P = .002). CTX-II concentrations did not differ between the first three-time points (P > .99) but significantly increased at 4 weeks post-surgery (P < .01). ACL reconstruction appears to reinitiate an inflammatory response followed by an increase in markers for cartilage degradation. ACL reconstruction appears to initiate a second "inflammatory hit" resulting in increased chondral breakdown suggesting that post-operative chondroprotection may be needed.

An Expert Consensus Statement on the Management of Large Chondral and Osteochondral Defects in the Patellofemoral Joint.

BACKGROUND: Cartilage lesions of the patellofemoral joint constitute a frequent abnormality. Patellofemoral conditions are challenging to treat because of complex biomechanics and morphology. PURPOSE: To develop a consensus statement on the functional anatomy, indications, donor graft considerations, surgical treatment, and rehabilitation for the management of large chondral and osteochondral defects in the patellofemoral joint using a modified Delphi technique. STUDY DESIGN: Consensus statement. METHODS: A working group of 4 persons generated a list of statements related to the functional anatomy, indications, donor graft considerations, surgical treatment, and rehabilitation for the management of large chondral and osteochondral defects in the patellofemoral joint to form the basis of an initial survey for rating by a group of experts. The Metrics of Osteochondral Allografts (MOCA) expert group (composed of 28 high-volume cartilage experts) was surveyed on 3 occasions to establish a consensus on the statements. In addition to assessing agreement for each included statement, experts were invited to propose additional statements for inclusion or to suggest modifications of existing statements with each round. Predefined criteria were used to refine statement lists after each survey round. Statements reaching a consensus in round 3 were included within the final consensus document. RESULTS: A total of 28 experts (100% response rate) completed 3 rounds of surveys. After 3 rounds, 36 statements achieved a consensus, with over 75% agreement and less than 20% disagreement. A consensus was reached in 100.00% of the statements relating to functional anatomy of the patellofemoral joint, 88.24% relating to surgical indications, 100.00% relating to surgical technical aspects, and 100.00% relating to rehabilitation, with an overall consensus of 95.5%. CONCLUSION: This study established a strong expert consensus document relating to the functional anatomy, surgical indications, donor graft considerations for osteochondral allografts, surgical technical aspects, and rehabilitation concepts for the management of large chondral and osteochondral defects in the patellofemoral joint. Further research is required to clinically validate the established consensus statements and better understand the precise indications for surgery as well as which techniques and graft processing/preparation methods should be used based on patient- and lesion-specific factors.

Macrophage: A Potential Target on Cartilage Regeneration.

Cartilage lesions and osteoarthritis (OA) presents an ever-increasing clinical and socioeconomic burden. Synovial inflammation and articular inflammatory environment are the key factor for chondrocytes apoptosis and hypertrophy, ectopic bone formation and OA progression. To effectively treat OA, it is critical to develop a drug that skews inflammation toward a pro-chondrogenic microenvironment. In this narrative and critical review, we aim to see the potential use of immune cells modulation or cell therapy as therapeutic alternatives to OA patients. Macrophages are immune cells that are present in synovial lining, with different roles depending on their subtypes. These cells can polarize to pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes, being the latter associated with wound-healing by the production of ARG-1 and pro-chondrogenic cytokines, such as IL-10, IL-1RA, and TGF-b. Emerging evidence reveals that macrophage shift can be determined by several stimuli, apart from the conventional in vitro IL-4, IL-13, and IL-10. Evidences show the potential of physical exercise to induce type 2 response, favoring M2 polarization. Moreover, macrophages in contact with oxLDL have effect on the production of anabolic mediators as TGF-b. In the same direction, type II collagen, that plays a critical role in development and maturation process of chondrocytes, can also induce M2 macrophages, increasing TGF-b. The mTOR pathway activation in macrophages was shown to be able to polarize macrophages in vitro, though further studies are required. The possibility to use mesenchymal stem cells (MSCs) in cartilage restoration have a more concrete literature, besides, MSCs also have the capability to induce M2 macrophages. In the other direction, M1 polarized macrophages inhibit the proliferation and viability of MSCs and impair their ability to immunosuppress the environment, preventing cartilage repair. Therefore, even though MSCs therapeutic researches advances, other sources of M2 polarization are attractive issues, and further studies will contribute to the possibility to manipulate this polarization and to use it as a therapeutic approach in OA patients.

Rapid Progression of Knee Pain and Osteoarthritis Biomarkers Greatest for Patients with Combined Obesity and Depression: Data from the Osteoarthritis Initiative.

OBJECTIVE: To compare the progression of biochemical biomarkers of osteoarthritis (OA), knee pain, and function between nonobese patients (NON), obese patients without depression (OBESE), and obese patients with comorbid depression (O + D). DESIGN: Utilizing the FNIH OA Biomarkers Consortium dataset, we categorized knee OA patients into NON, OBESE, and O + D groups based on body mass index and Center for Epidemiological Studies-Depression (CES-D) scores. Subjective symptoms (Knee injury and Osteoarthritis Outcome Score Quality of Life subscale (KOOS QOL), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function scores, and the Short Form-12 (SF-12) Physical Component Score [PCS]) and objective measures of cartilage degradation and bone remodeling (urinary CTXII and CTXIα) were compared among groups at baseline and 2-year follow-up. RESULTS: Of the 600 patients, 282 (47%) were NON, 285 (47.5%) OBESE, and 33 (5.5%) O + D. The O + D group had significantly worse pain and function both at baseline and 2-year follow-up (P < 0.001 for all comparisons) as evidenced by self-reported measures on KOOS QOL, WOMAC Pain, WOMAC Physical Function, and SF-12 PCS. The O + D group also demonstrated significant increases in CTXII (P = 0.01) and CTXIα (P = 0.005), whereas the NON and OBESE groups did not. CONCLUSIONS: The combination of inferior knee pain, physical function, and significantly greater increases in biomarkers of cartilage degradation and bony remodelling suggest a more rapid progression for obese OA patients with comorbid depression. The link between systemic disease, inflammatory burden, and progressive cartilage degradation is in line with increasing concerns about a degenerative synovial environment in early osteoarthritic knees that progress to treatment failure with biologic restoration procedures.