Cost-utility analysis of early reconstruction surgery versus conservative treatment for anterior cruciate ligament injury in a lower-middle income country.

BACKGROUND: The ideal approach for treating anterior cruciate ligament (ACL) injury is still disputed. This study aimed to determine the more cost-effective strategy by comparing early ACL reconstruction (ACLR) surgery to conservative treatment (rehabilitation with optional delayed reconstruction) for ACL injury in a lower/middle-income country (LMIC), Indonesia. METHODS: A decision tree model was constructed for cost-utility analysis of early ACLR versus conservative treatment. The transition probabilities between states were obtained from the literature review. Utilities were measured by the EQ-5D-3 L from a prospective cohort study in a local hospital. The costs were obtained from a previous study that elaborated on the burden and cost of ACLR in Indonesia. Effectiveness was expressed in quality-adjusted life years gained (QALYs). Principal outcome measure was the incremental cost-effectiveness ratios (ICER). Willingness-to-pay was set at US$12,876 - three times the Indonesian GDP per capita in 2021 - the currently accepted standard in Indonesia as suggested by the World Health Organization Choosing Interventions that are Cost-Effective criterion (WHO-CHOICE). RESULTS: The early ACLR group showed an incremental gain of 0.05 QALYs over the conservative treatment group, with a higher overall cost to society of US$976. The ICER of ACLR surgery was US$19,524 per QALY, above the WTP threshold of US$12,876. The ICER was sensitive to cost of conservative treatment, cost of ACLR, and rate of cross-over to delayed ACLR numbers in the conservative treatment group. Using the WTP threshold of US$12,876, the probability of conservative treatment being preferred over early ACLR was 64%. CONCLUSIONS: Based on the current model, early ACLR surgery does not seem more cost-effective compared to conservative treatment for ACL injury patients in Indonesia. Because the result was sensitive to the rate of cross-over probabilities from the conservative treatment alone to delayed ACLR, a future study with a long-term perspective is needed to further elucidate its impact.

Comparison of femoral tunnel position and knee function in anterior cruciate ligament reconstruction: a retrospective cohort study using measuring-fluoroscopy method versus bony marker method.

BACKGROUND: Previous studies have shown that surgical technique errors especially the wrong bone tunnel position are the primary reason for the failure of anterior cruciate ligament (ACL) reconstruction. In this study, we aimed to compare the femoral tunnel position and impact on knee function during the ACL reconstruction using measuring combined with fluoroscopy method and bony marker method for femoral tunnel localization. METHODS: A retrospective cohort study of patients undergoing ACL reconstruction using the bony marker method or measuring combined with fluoroscopy for femoral tunnel localization was conducted between January 2015 and January 2020. A second arthroscopic exploration was performed more than 1 year after surgery. Data regarding patient demographics, the femoral tunnel position, results of the Lysholm score, the International Knee Documentation Committee (IKDC) score, KT-1000 side-to-side difference, pivot shift grade, and Lachman grade of the knee were collected. RESULTS: A total of 119 patients were included in the final cohort. Of these, 42 cases were in the traditional method group, and 77 cases were in the measuring method group. The good tunnel position rate was 26.2% in the traditional method group and 81.8% in the measuring method group (p < 0.001). At the final follow-up, the Lysholm and IKDC scores were significantly greater in the measuring method group than the traditional method group (IKDC: 84.9 ± 8.4 vs. 79.6 ± 6.4, p = 0.0005; Lysholm: 88.8 ± 6.4 vs. 81.6 ± 6.4, p < 0.001). Lachman and pivot shift grades were significantly greater in the measuring method group (p = 0.01, p = 0008). The results of KT-1000 side-to-side differences were significantly better in the measuring method group compared with those in the traditional method group (p < 0.001). CONCLUSIONS: The combination of the measuring method and intraoperative fluoroscopy resulted in a concentrated tunnel position on the femoral side, a high rate of functional success, improved knee stability, and a low risk of tunnel deviation. This approach is particularly suitable for surgeons new to ACL reconstructive surgery.

Dynamic radiostereometry can objectively quantify the kinematic laxity patterns and rotation instability of the knee during a pivot-shift test.

PURPOSE: The pivot-shift test is used to clinically assess knee instability in patients with anterior cruciate ligament (ACL) lesions; however, it has low interobserver reliability. Dynamic radiostereometry (dRSA) is a highly precise and noninvasive method for the objective evaluation of joint kinematics. The purpose of this study was to quantify precise knee kinematics during a pivot-shift test using dRSA imaging. METHOD: Eight human donor legs, including hemipelvises, were evaluated. Arthroscopic intervention was performed inducing ligament lesions in the ACL, and anterolateral ligament (ALL) section was performed as a capsular incision. The pivot-shift test was recorded with dRSA on knees with intact ligaments, ACL-deficient and ACL + ALL-deficient knees. RESULTS: A pivot-shift pattern was identifiable after ligament lesion, as a change in tibial posterior drawer velocity from 7.8 mm/s (95% CI: 3.7; 11.9) in ligament intact knees to 30.4 mm/s (95% CI 23.0; 38.8) after ACL lesion to 35.1 mm/s (95% CI 23.4; 46.7) after combined ACL-ALL lesion. The anterior-posterior drawer excursion increased from 2.8 mm (95% CI 2.1; 3.4) in ligament intact knees to 7.2 mm (95% CI 5.5; 8.9) after ACL lesion to 7.6 mm (95% CI 5.5; 9.8) after combined lesion. A statistically significant increase in tibial external rotation towards the end of the pivot-shift motion was observed when progressing from intact to ACL + ALL-deficient knees (p < 0.023). CONCLUSION: This experimental study demonstrates the feasibility of dRSA to objectively quantify the kinematic laxity patterns of the knee during the pivot-shift test. The dynamic parameters obtained through dRSA revealed the kinematic changes from ACL to combined ACL-ALL ligament lesion. LEVEL OF EVIDENCE: Not applicable.

Externally validated treatment algorithm acceptably predicts nonoperative treatment success in patients with anterior cruciate ligament rupture.

PURPOSE: This study aims to develop and externally validate a treatment algorithm to predict nonoperative treatment success or failure in patients with anterior cruciate ligament (ACL) rupture. METHODS: Data were used from two completed studies of adult patients with ACL ruptures: the Conservative versus Operative Methods for Patients with ACL Rupture Evaluation study (development cohort) and the KNee osteoArthritis anterior cruciate Ligament Lesion study (validation cohort). The primary outcome variable is nonoperative treatment success or failure. Potential predictor variables were collected, entered into the univariable logistic regression model and then incorporated into the multivariable logistic regression model for constructing the treatment algorithm. Finally, predictive performance and goodness-of-fit were assessed and externally validated by discrimination and calibration measures. RESULTS: In the univariable logistic regression model, a stable knee measured with the pivot shift test and a posttrauma International Knee Documentation Committee (IKDC) score <50 were predictive of needing an ACL reconstruction. Age >30 years and a body mass index > 30 kg/m2 were predictive for not needing an ACL reconstruction. Age, pretrauma Tegner score, the outcome of the pivot shift test and the posttrauma IKDC score are entered into the treatment algorithm. The predictability of needing an ACL reconstruction after nonoperative treatment (discrimination) is acceptable in both the development and the validation cohort: area under the curve = resp. 0.69 (95% confidence interval [CI]: 0.58-0.81) and 0.68 (95% CI: 0.58-0.78). CONCLUSION: This study shows that the treatment algorithm can acceptably predict whether an ACL injury patient will have a(n) (un)successful nonoperative treatment (discrimination). Calibration of the treatment algorithm suggests a systematical underestimation of the need for ACL reconstruction. Given the limitations regarding the sample size of this study, larger data sets must be constructed to improve the treatment algorithm further. LEVEL OF EVIDENCE: Level II.

The early peak knee abduction moment waveform is a novel risk factor predicting anterior cruciate ligament injury in young athletes: A prospective study.

PURPOSE: In this study, prospective data were used to evaluate whether the early peak knee abduction moment waveform is associated with the risk of anterior cruciate ligament (ACL) injury. METHODS: Biomechanical data from 84 athletes who participated in the study as adolescents were analysed after cross-referencing national health registry data to confirm ACL reconstruction in the subsequent years. The knee abduction moment waveform shape was obtained with cluster analysis for the first 100 ms of a cutting manoeuvre (1776 trials in total) and classified as either containing an early peak knee abduction moment or not, and the odds ratio for later ACL injury was then calculated. Additionally, discrete kinematic and kinetic variables were extracted, and tested against the risk of ACL injury using mixed model logistic regression. RESULTS: Of 84 athletes, 8 (all female) sustained a total of 13 ACL injuries in the years after motion analysis data collection. Six clusters of knee abduction moment waveform shapes were identified. Two clusters containing 446 trials were classified as an early peak knee abduction waveform. This waveform was associated with a 7.2-fold increase in the risk of ACL injury (95% confidence interval: 2.4-24.6; p < 0.001). Of the kinematic and kinetic variables tested, only the knee abduction angle at initial contact was associated with an increased risk of ACL injury (p < 0.001). CONCLUSION: This is the first study to confirm the association between the early peak knee abduction moment waveform and the risk of ACL injury. Using waveforms, instead of discrete peak values of the knee abduction moment, may better represent risky movement patterns. Replicating these findings in a larger cohort will support the use of this method to screen athletes for risk and guide targeted preventive interventions and their efficacy. LEVEL OF EVIDENCE: Level II.

An anteromedial stabilization procedure has the most protective effect on the anterior cruciate ligament in tibial external rotation. A human knee model study.

INTRODUCTION: Anterior cruciate ligament (ACL) reconstruction remains associated with the risk of re-rupture and persisting rotational instability. Additional extraarticular anterolateral stabilization procedures stabilize the tibial internal rotation and lead to lower ACL failure rate and improved knee stability. However, data for additional stabilization of tibial external rotation is lacking and the importance of an anteromedial stabilization procedure is less well evaluated. Aim of this study is to investigate the influence of an extraarticular anteromedial stabilization procedure for the stabilization of the tibial external rotation and protection of the ACL from these rotational forces. METHODS: Internal and external rotations of the tibia were applied to a finite element (FE) model with anatomical ACL, posterior cruciate ligament (PCL), lateral collateral ligament (LCL), medial collateral ligament (MCL) and intact medial and lateral meniscus. Five additional anatomic structures (Anteromedial stabilization/anteromedial ligament, AML, augmented superficial medial collateral ligament, sMCL, posterior oblique ligament, POL, anterolateral ligament, ALL, and popliteal tendon, PLT) were added to the FE model separately and then combined. The force histories within all structures were measured and determined for each case. RESULTS: The anteromedial stabilization or imaginary AML was the main secondary stabilizer of tibial external rotation (90% of overall ACL force reduction). The AML reduced the load on the ACL by 9% in tibial external rotation which could not be achieved by an augmented sMCL (-1%). The AML had no influence in tibial internal rotation (-1%). In the combined measurements with all additional structures (AML, ALL, PLT, POL) the load on the ACL was reduced by 10% in tibial external rotation. CONCLUSION: This study showed that an additional anteromedial stabilization procedure secures the tibial external rotation and has the most protective effect on the ACL during these external rotational forces.

Knee osteoarthritis, joint laxity and PROMs following conservative management versus surgical reconstruction for ACL rupture: a meta-analysis.

INTRODUCTION: Patients whose rupture of the anterior cruciate ligament (ACL) can be managed conservatively or undergo reconstruction surgery. SOURCE OF DATA: Current scientific literature published in Web of Science, PubMed and Scopus. AREAS OF AGREEMENT: Several studies published by July 2022 compare surgical and conservative management following ACL rupture. The latest evidence suggests that surgical management may expose patients to an increased risk of early-onset knee osteoarthritis (OA). AREAS OF CONTROVERSY: The state of art does not recommend a systematic ACL reconstruction to all patients who tore their ACL. After the initial trauma, surgical reconstruction may produce even greater damage to the intra-articular structures compared to conservative management. GROWING POINTS: The state of art does not recommend systematic surgical reconstruction to all patients who tore their ACL. The present study compared surgical reconstruction versus conservative management for primary ACL ruptures in terms of joint laxity, patient reported outcome measures (PROMs) and rate of osteoarthritis. AREAS TIMELY FOR DEVELOPING RESEARCH: ACL reconstruction provides significant improvement in joint laxity compared to conservative management, but is associated with a significantly greater rate of knee osteoarthritis, despite similar results at PROM assessment.

Early patellofemoral cartilage and bone pathology in a rat model of noninvasive anterior cruciate ligament rupture.

OBJECTIVE: Anterior cruciate ligament rupture (ACLR) is a risk factor for the development of post-traumatic osteoarthritis (PTOA). While PTOA in the tibiofemoral joint compartment is well-characterized, very little is known about pathology in the patellofemoral compartment after ACL injury. Here, we evaluated the extent to which ACLR induces early patellofemoral joint damage in a rat model. METHODS: Adult female Lewis rats were randomized to noninvasive ACLR or Sham. Two weeks post-injury, contrast-enhanced micro-computed tomography (µCT) of femoral and patellar cartilage was performed using 20% v/v ioxaglate. Morphometric parameters of femoral trochlear and patellar cartilage, subchondral bone, and trabecular bone were derived from µCT. Sagittal Safranin-O/Fast-Green-stained histologic sections were graded using the OARSI score in a blinded fashion. RESULTS: Cartilage and bone remodelling consistent with an early PTOA phenotype were observed in both femoral trochleas and patellae. ACLR caused osteophyte formation of the patella and pathology in the superficial zone of articular cartilage, including surface fibrillation, fissures, increased cellularity, and abnormal chondrocyte clustering. There were significant increases in thickness of patellar and trochlear cartilage. Loss of subchondral bone thickness, bone volume fraction, and tissue mineral density, as well as changes to patellar and trochlear trabecular microarchitecture, were indicative of catabolic bone remodelling. Several injury-induced changes, including increased cartilage thickness and trabecular spacing and decreased trabecular number were more severe in the patella compared to the trochlea. CONCLUSION: The patellofemoral joint develops mild but evident pathology in the early period following ACL rupture, extending the utility of this model to the study of patellofemoral PTOA.

Distribution of bone tunnel positions and treatment efficacy of bone landmark positioning method for anatomical reconstruction of the anterior cruciate ligament: a case control study.

BACKGROUND: This study aimed to investigate the distribution of femoral tunnel and explore the influences of bone tunnel positions on knee functions. The bone landmark positioning method was used to position the femoral tunnel during the anatomical reconstruction surgery in patients with anterior cruciate ligament (ACL) rupture. METHODS: Data of patients who underwent anatomical reconstruction of the ACL between January 2015 and July 2018, were retrospectively analyzed. The distribution of the femoral tunnel was recorded on 3-D CT after surgery. The tunnel positions were classified into good and poor position groups based on whether the position was in the normal range (24-37% on the x-axis and 28-43% on the y-axis). The Lysholm and IKDC scores, KT-1000 side-to-side difference, pivot shift test and Lachman test results of the knee joints were recorded, and then the differences in knee joint functions between the two groups were analyzed. RESULTS: 84 eligible patients (84 knees) were finally included in this study. Twenty-two and 62 of the patients were categorized in the good and poor position groups, respectively, and the rate of good position was 26.2%. The distribution of bone tunnel was as follows: (x-axis) deep position in 10 patients (12%), normal position in 58 patients (69%), and shallow position in 16 patients (19%); (y-axis) high position in 54 patients (64%), normal position in 26 patients (31%), and low position in 4 patients (5%). 1 year later, the Lysholm and IKDC scores were significantly better in the good position group (P < 0.05), the KT-1000 side to side difference, the pivot shift test and Lachman test results were better in the good position group (P < 0.05). CONCLUSIONS: The bone tunnels were found to be distributed in and beyond the normal range using the bone landmark method to position the femoral tunnel in the single-bundle anatomical reconstruction of ACL, while the rate of good bone tunnel position was low. The knee joint function scores and stability were lower in patients with poor position of the femoral tunnel.

The "Bankart knee": high-grade impression fractures of the posterolateral tibial plateau lead to increased translational and anterolateral rotational instability of the ACL-deficient knee.

PURPOSE: The aim of this biomechanical cadaver study was to evaluate the effects of high-grade posterolateral tibia plateau fractures on the kinematics of anterior cruciate ligament (ACL)-deficient joints; it was hypothesized that, owing to the loss of the integrity of the osseous support of the posterior horn of the lateral meniscus (PHLM), these fractures would influence the biomechanical function of the lateral meniscus (LM) and consequently lead to an increase in anterior translational and anterolateral rotational (ALR) instability. METHODS: Eight fresh-frozen cadaveric knees were tested using a six-degree-of-freedom robotic setup (KR 125, KUKA Robotics, Germany) with an attached optical tracking system (Optotrack Certus Motion Capture, Northern Digital, Canada). After the passive path from 0 to 90° was established, a simulated Lachman test and pivot-shift test as well as external rotation (ER) and internal rotation (IR) were applied at 0°, 30°, 60° and 90° of flexion under constant 200 N axial loading. All of the parameters were initially tested in the intact and ACL-deficient states, followed by two different types of posterolateral impression fractures. The dislocation height was 10 mm, and the width was 15 mm in both groups. The intraarticular depth of the fracture corresponded to half of the width of the posterior horn of the lateral meniscus in the first group (Bankart 1) and 100% of the meniscus width in the second group (Bankart 2). RESULTS: There was a significant decrease in knee stability after both types of posterolateral tibial plateau fractures in the ACL-deficient specimens, with increased anterior translation in the simulated Lachman test at 0° and 30° of knee flexion (p = 0.012). The same effect was seen with regard to the simulated pivot-shift test and IR of the tibia (p = 0.0002). In the ER and posterior drawer tests, ACL deficiency and concomitant fractures did not influence knee kinematics (n.s.). CONCLUSION: This study demonstrates that high-grade impression fractures of the posterolateral aspect of the tibial plateau increase the instability of ACL-deficient knees and result in an increase in translational and anterolateral rotational instability.

Spontaneous healing of acute ACL ruptures: rate, prognostic factors and short-term outcome.

INTRODUCTION: Anterior cruciate ligament (ACL) reconstruction is considered the first line treatment in ACL rupture. However, some patients return to high intensity sport activities and show a normal knee function without ACL reconstruction. Therefore, aim of this study was to evaluate the rate and prognostic factors of spontaneous healing in patients with ACL rupture and the short-term functional outcome. METHODS: The rate, prognostic factors and short-term functional results of spontaneous healing in patients with ACL rupture were evaluated in 381 patients. Morphology of ACL rupture and extent of posterior tibial slope (PTS) were classified by MR- and x-ray imaging. In patients with normal knee stability in anesthesia examination and healed ACL during the arthroscopy 6 weeks after trauma ACL reconstruction was canceled. IKDC -, Tegner Activity Score, KT 1000 testing and radiological characteristics were collected 12 months postoperatively in these patients. RESULTS: 14.17% of the patients with ACL rupture showed a spontaneous healing after 6 weeks. Femoral ACL-rupture (p < 0.02) with integrity of ligament stump > 50% (p < 0.001), without bundle separation (p < 0.001) and decreased PTS (p < 0.001) was found significantly more often in patients with a spontaneous healed ACL. The average IKDC score was high at 84,63 in patients with healed ACL at 1 year follow-up, but KT 1000 testing was inferior compared to non-injured side. CONCLUSION: Spontaneous healing of a ruptured ACL happened in 14% of the patients. Especially in low-demand patients with femoral single bundle lesions without increased posterior tibial slope delayed ACL surgery should be considered to await the possibility for potential spontaneous ACL healing.

Etiology of posterior meniscus root tears: medial vs. lateral.

PURPOSE: The aim of this study was to generate more information on the etiology and pathogenesis of medial (MM) and lateral (LM) meniscus root tears. Our hypothesis was that root tears of the MM predominantly result from degenerative damage, whereas root injuries of the LM are mainly of traumatic origin. METHODS: Consecutively, 53 patients with a root tear of the medial meniscus (MMRT) and 51 patients with a root tear of the lateral meniscus (LMRT) were included in this study. The diagnosis was confirmed radiologically by MRI as well as arthroscopically. In addition to patient-specific data such as age, BMI and trauma history, the leg axis was determined and accompanying injuries (ligamentous and chondrogenic) were documented. RESULTS: The mean age of the MMRT group was 57.2 (± 11.2) years, and that of the LMRT group 33.9 (± 11.4) years. The BMI was significantly higher in the MMRT group compared to the LMRT (30.5 vs. 25.1). 82.4% of patients in the LMRT group demonstrated an accompanying anterior cruciate ligament (ACL) rupture, whereas only 5.7% of the MMRT were associated with an ACL injury. A trauma was described in only 13.2% of patients of the MMRT group in contrast to 88.2% of the LMRT group. An extrusion > 3 mm of the MM in the coronal plane of MRI images could be detected in 86.8% of patients, whereas in the LMRT group, it was 15.7%. The mechanical varus angle was 5.6° in the MMRT group and 2.4° in the LMRT group. The rate and degree of concomitant cartilage damage in the affected compartment was significantly higher in the group with medial root injuries than in the group with lateral root tears. CONCLUSIONS: The root injuries of the MM and LM show significant differences in terms of patient age, etiology and accompanying injuries. Root injuries to the medial meniscus are mostly of non-traumatic origin and more likely to occur in the context of medial osteoarthritis and varus deformity of the knee. Lateral root tears tend to be predominantly traumatic and are frequently associated with ACL ruptures. However, in the MMRT group, a small subgroup with a traumatic etiology and in the LMRT group a small subgroup of patients with non-traumatic etiology could be identified. LEVEL OF EVIDENCE: III.

Posterior tibial slope (PTS) ≥ 10 degrees is a risk factor for further anterior cruciate ligament (ACL) injury; BMI is not.

PURPOSE: This case-control study aimed to assess the influence of BMI and PTS on subsequent ACL injury affecting either ACL graft or the native ACL of the contralateral knee after primary ACL reconstruction. METHODS: A retrospective case-control study was performed using a cohort of patients who underwent arthroscopic ACL reconstruction between 2010 and 2020 using the same surgical procedure: Hamstring tendon autograft. The study group (group I) included all the patients (n = 94) during this period who sustained a subsequent ACL injury. The control group (group II) consisted of 94 patients randomly selected (matched Group I in terms of sex, age, and ACL graft) who did not sustain any further ACL injury. PTS was measured by two blinded surgeons on lateral knee view radiographs of the operated knee after primary ACL. BMI in kg/m2 was measured during the preoperative anesthesia consultation. Exclusion criteria were: non-true or rotated lateral knee radiographs of the operated knee post-ACLR, associated knee ligament injury requiring surgical management, iterative knee surgeries, open growth plate, and related fracture. RESULTS: The mean posterior tibial slope in group I was 7.5° ± 2.9, and 7.2° ± 2.0 in group II. A PTS angle cutoff was set at 10 degrees. The rate of patients showing a PTS ≥ 10° was significantly higher in group I compared to group II (p < 0.01). Patients with PTS ≥ 10° were 5.7 times more likely to sustain a subsequent ACL injury, (OR: 5.7 95% CI[1.858-17.486]). The Average BMI in group I was 24.5 ± 3.7 kg.m-2 compared to group II which was 23.3 ± 3.0 kg.m-2. There were no significant differences in any of the four BMI categories between both groups (p value 0.289). A series of BMI cut-offs were also analyzed at 23 to30 kg/m2, and there was no significant difference between both groups. CONCLUSIONS: A posterior tibial slope equal to or above 10 degrees measured on lateral knee radiographs was associated with 5.7 times higher risk of ACL graft rupture or contralateral native ACL injury; however, BMI was not.

Influence of type I collagen polymorphisms and risk of anterior cruciate ligament rupture in athletes: a case-control study.

BACKGROUND: Anterior cruciate ligament (ACL) rupture is a common and severe knee injury in sports and occurs mostly due to noncontact injuries. There is an increasing amount of evidence associating ACL rupture to single nucleotide polymorphisms (SNPs), and SNPs in the collagen type I genes can change its expression and tissue mechanical features. This study aimed to investigate the association between SNPs in COL1A1 and COL1A2 with sports-related ACL tears. METHODS: A total of 338 athletes from multiple sports modalities were analyzed: 146 were diagnosed with ACL rupture or underwent an ACL reconstruction surgery and 192 have no musculoskeletal injuries. SNPs were genotyped using validated TaqMan assays. The association of the polymorphisms with ACL rupture was evaluated by a multivariable logistic regression model, using odds ratios (OR) and 95% confidence intervals (CI). RESULTS: The age, sport modality, and training location were associated with an increased risk of a non-contact ACL tear. COL1A2 SNPs (rs42524 CC and rs2621215 GG) were associated with an increased risk of non-contact ACL injury (6 and 4-fold, respectively). However, no significant differences were detected in the distribution of COL1A1 rs1107946 and COL1A2 rs412777 SNPs between cases and controls. There was a protective association with ACL rupture (OR = 0.25; 95% CI = 0.07-0.96) between COL1A1 rs1107946 (GT or TT) and the wildtype genotypes of the three COL1A2 (rs412777, rs42524, rs2621215). COL1A2 rs42524 and rs2621215 SNPs were associated with non-contact ACL risk. CONCLUSION: The combined analysis of COL1A1-COL1A2 genotypes suggests a gene-gene interaction in ACL rupture susceptibility.

Canine ACL rupture: a spontaneous large animal model of human ACL rupture.

BACKGROUND: Anterior cruciate ligament (ACL) rupture in humans is a common condition associated with knee pain, joint instability, and secondary osteoarthritis (OA). Surgical treatment with an intraarticular graft provides reasonable outcomes at mid and long-term follow-up. Non-modifiable and modifiable factors influence risk of ACL rupture. The etiology, mechanobiology, causal biomechanics, and causal molecular pathways are not fully understood. The dog model has shared features of ACL rupture that make it a valuable spontaneous preclinical animal model. In this article, we review shared and contrasting features of ACL rupture in the two species and present information supporting spontaneous canine ACL rupture as a potentially useful preclinical model of human ACL rupture with a very large subject population. RESULTS: ACL rupture is more common in dogs than in humans and is diagnosed and treated using similar approaches to that of human patients. Development of OA occurs in both species, but progression is more rapid in the dog, and is often present at diagnosis. Use of client-owned dogs for ACL research could reveal impactful molecular pathways, underlying causal genetic variants, biomechanical effects of specific treatments, and opportunities to discover new treatment and prevention targets. Knowledge of the genetic contribution to ACL rupture is more advanced in dogs than in humans. In dogs, ACL rupture has a polygenetic architecture with moderate heritability. Heritability of human ACL rupture has not been estimated. CONCLUSION: This article highlights areas of One Health research that are particularly relevant to future studies using the spontaneous canine ACL rupture model that could fill gaps in current knowledge.

Satisfactory patient-reported outcomes at 5 years following primary repair with suture tape augmentation for proximal anterior cruciate ligament tears.

PURPOSE: An enhanced understanding of anterior cruciate ligament (ACL) healing and advancements in arthroscopic instrumentation has resulted in a renewed interest in ACL repair. Augmentation of a ligament repair with suture tape reinforces the ligament and acts as a secondary stabilizer. This study assesses the 5-year patient-reported outcomes of primary repair with suture tape augmentation for proximal ACL tears. METHODS: Thirty-seven consecutive patients undergoing ACL repair with suture tape augmentation for an acute proximal rupture were prospectively followed up for a minimum of 5 years. Patients with midsubstance and distal ruptures, poor ACL tissue quality, retracted ACL remnants and multiligament injuries were excluded. Patient-reported outcome measures were collated using the Knee Injury and Osteoarthritis Outcomes Score (KOOS), Visual Analogue Pain Scale (VAS-pain), Veterans RAND 12-Item Health Survey (VR-12) and the Marx Activity Scale. Patients with a re-rupture were identified. RESULTS: Three patients were lost to follow-up leaving 34 patients in the final analysis (91.9%). The mean KOOS at 5 years was 88.5 (SD 13.8) which improved significantly from 48.7 (SD 18.3) preoperatively (p < 0.01). The VAS score improved from 2.3 (SD 1.7) to 1.0 (SD 1.5) and the VR-12 score improved from 35.9 (SD 10.3) to 52.4 (SD 5.9) at 5 years (p < 0.01). However, the Marx activity scale decreased from 12.4 (SD 3.4) pre-injury to 7.3 (SD 5.2) at 5 years (p = 0.02). Six patients had a re-rupture (17.6%) and have since undergone a conventional ACL reconstruction for their revision surgery with no issues since then. These patients were found to be younger and have higher initial Marx activity scores than the rest of the cohort (p < 0.05). CONCLUSION: Primary repair with suture tape augmentation for proximal ACL tears demonstrates satisfactory outcomes in 28 patients (82.4%) at 5-year follow-up. Six patients sustained a re-rupture and have no ongoing problems following treatment with a conventional ACL reconstruction. These patients were significantly younger and had higher initial Marx activity scores. LEVEL OF EVIDENCE: Level IV.

Lateral femoral notch sign and posterolateral tibial plateau fractures and their associated injuries in the setting of an anterior cruciate ligament rupture.

INTRODUCTION: ACL injury is one of the most common injuries of the knee joint in sports. As accompanying osseous injuries of the ACL rupture a femoral impression the so-called lateral femoral notch sign and a posterolateral fracture of the tibial plateau are described. However, frequency, concomitant ligament injuries and when and how to treat these combined injuries are not clear. There is still a lack of understanding with which ligamentous concomitant injuries besides the anterior cruciate ligament injury these bony injuries are associated. MATERIALS AND METHODS: One hundred fifteen MRI scans with proven anterior cruciate ligament rupture performed at our center were retrospectively evaluated for the presence of a meniscus, collateral ligament injury, a femoral impression, or a posterolateral impression fracture. Femoral impressions were described according to their local appearance and posterolateral tibial plateau fractures were described using the classification of Menzdorf et al. RESULTS: In 29 cases a significant impression in the lateral femoral condyle was detected. There was a significantly increased number of lateral meniscal (41.4% vs. 18.6% p = 0.023) and medial ligament (41.4% vs. 22.1%; p = 0.040) injuries in the group with a lateral femoral notch sign. 104 patients showed a posterolateral bone bruise or fracture of the tibial plateau. Seven of these required an intervention according to Menzdorf et al. In the group of anterior cruciate ligament injuries with posterolateral tibial plateau fracture significantly more lateral meniscus injuries were seen (p = 0.039). CONCLUSION: In the preoperative planning of ACL rupture accompanied with a positive femoral notch sign, attention should be paid to possible medial collateral ligament and lateral meniscus injuries. As these are more likely to occur together. A posterolateral impression fracture of the tibial plateau is associated with an increased likelihood of the presence of a lateral meniscal injury. This must be considered in surgical therapy and planning and may be the indication for necessary early surgical treatment.

Higher sensitivity with the lever sign test for diagnosis of anterior cruciate ligament rupture in the emergency department.

INTRODUCTION: The objective of this study was to assess the diagnostic value of the "lever sign test" to diagnose ACL rupture and to compare this test to the two most commonly used, the Lachman and anterior drawer test. METHOD: This prospective study was performed in the ED of the Cliniques Universitaires Saint-Luc (Brussels, Belgium) from March 2017 to May 2019. 52 patients were included undergoing knee trauma, within 8 days, with an initial radiograph excluding a fracture (except Segond fracture or tibial spine fracture). On clinical investigation, patients showed a positive lever sign test and/or a positive Lachman test and/or a positive anterior drawer test. Exclusion criteria were a complete rupture of the knee extensor mechanism and patellar dislocation. All the physicians involved in this study were residents in training. An MRI was performed within 3 weeks for all included patients after the clinical examination. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were investigated for all three tests with MRI used as our reference standard. RESULTS: Forty out of 52 patients suffered an ACL rupture (77%) and 12 did not (23%). The sensitivity, specificity, PPV and NPV of the lever sign test were respectively 92.5%, 25% 82% and 50%. Those of the Lachman test were 54%, 54.5%, 81% and 25%, and those of the anterior drawer test were 56%, 82%, 90.5% and 37.5%. Twelve out of 40 ACL ruptures (30%) were diagnosed exclusively with a positive lever sign test. CONCLUSION: When investigating acute ACL ruptures (< 8 days) in the ED, the lever sign test offers a sensitivity of 92.5%, far superior to that of other well-known clinical tests. The lever sign test is relatively pain-free, easy to perform and its visual interpretation requires less experience. Positive lever sign test at the ED should lead to an MRI to combine high clinical sensitivity with high MRI specificity.

Does the Extension Torque Control Differ between Injured and Uninjured Knees of ACL-Deficient Individuals?

Background: Knee extension torque control decreases after anterior cruciate ligament (ACL) rupture. There is a controversy in neuromuscular control changes on the uninvolved side. We intended to evaluate the steadiness and accuracy of quadriceps muscle control in the healthy and deficient sides of people with acute ACL rupture. Methods: In this cross-sectional study, thirteen men with ACL rupture (age: 27.8±7.0, body mass index (BMI): 24.7±2.25: 24.7, days from injury: 48.1±21.3) participated in the study. We measured quadriceps force control, which is quantitatively assessed by the standard deviation (SD) of joint torque for a predefined submaximal target. The accuracy of muscular control or performance of quadriceps is commonly quantified by the root mean square of error (RMSE) was also measured. A two-way analysis of variance was conducted to assess SD and RMSE of two levels of quadriceps contraction (30% of muscle voluntary contraction (MVC), 50% of MVC) across both healthy and deficient knees. Results: There was a significant main effect for SD and RMSE of MVC percentage (p<0.001). SD of quadriceps torque in 50% of MVC (1.44 ± 0.13) was higher than 30% of MVC (0.88 ± 0.1). In contrast, there was no significant main effect for SD and RMSE of knee condition. Conclusion: After unilateral ACL rupture, the neuromuscular system becomes defected and quadriceps muscle control is then reduced in the healthy side. Therefore, the healthy side is also vulnerable to ligamentous damage. Besides, with the increasing intensity of physical activities, neuromuscular control decreases and the risk of re-injury rises.

Bromodomain-containing-protein-4 and cyclin-dependent-kinase-9 inhibitors interact synergistically in vitro and combined treatment reduces post-traumatic osteoarthritis severity in mice.

OBJECTIVE: Joint injury rapidly induces expression of primary response genes (PRGs), which activate a cascade of secondary genes that destroy joint tissues and initiate post-traumatic osteoarthritis (PTOA). Bromodomain-containing-protein-4 (Brd4) and cyclin-dependent-kinase-9 (CDK9) cooperatively control the rate-limiting step of PRG transactivation, including pro-inflammatory genes. This study investigated whether Brd4 and CDK9 inhibitors suppress inflammation and prevent PTOA development in vitro and in a mouse PTOA model. METHODS: The effects of Brd4 and CDK9 inhibitors (JQ1 and Flavopiridol) on PRG and associated secondary damage were rigorously tested in different settings. Short-term effects of inflammatory stimuli (IL-1ß, IL-6, TNF) on human chondrocyte PRG expression were assessed by RT-PCR and microarray after 5-h. We quantified glycosaminoglycan release from IL-1ß-treated bovine cartilage explants after 3-6 days, and osteoarthritic changes in mice after ACL-rupture using RT-PCR (2-24hrs), in vivo imaging of MMP activity (24hrs), AFM-nanoindentation (3-7days), and histology (3days-4wks). RESULTS: Flavopiridol and JQ1 inhibitors act synergistically, and a combination of both almost completely prevented the activation of most IL-1ß-induced PRGs in vitro by microarray analysis, and prevented IL-1ß-induced glycosaminoglycan release from cartilage explants. Mice given the drug combination showed reduced IL-1ß and IL-6 expression, less in vivo MMP activity, and lower synovitis (1.5 vs 4.9) and OARSI scores (2.8 vs 6.0) than untreated mice with ACL-rupture. CONCLUSIONS: JQ1 and Flavopiridol work synergistically to reduce injury response after joint trauma, suggesting that targeting Brd4 and/or CDK9 could be a viable strategy for PTOA prevention and treatment of early OA.