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.

Early Anterior Cruciate Ligament Treatment Might Be Crucial for Acute Combined Anterior Cruciate Ligament and Medial Collateral Ligament Injuries: A Systematic Review of the Various Treatment Strategies.

PURPOSE: To assess the outcomes of acute, combined, complete anterior cruciate ligament (ACL) and medial collateral ligament (MCL) injuries in the literature. METHODS: A literature search using PubMed, Embase, Scopus, and Cochrane Reviews was performed following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines. The inclusion criteria were studies reporting outcomes of complete ACL-MCL injuries at a minimum of 12 months' follow-up. Data were presented as ranges. RESULTS: Twenty-seven studies with 821 patients were included (mean age, 29 years; 61% male patients; mean follow-up period, 27 months). There were 4 randomized trials, 10 Level III studies, and 13 Level IV studies. Nine different strategies were noted, of which nonoperative MCL treatment with acute ACL reconstruction and acute MCL repair with acute ACL reconstruction were most commonly performed. Nonoperative MCL-ACL treatment and acute MCL repair with nonoperative ACL treatment led to low rates of valgus stability at 30° of flexion (27%-68% and 36%-77%, respectively) compared with acute ACL reconstruction with either nonoperative MCL treatment (80%-100%), acute MCL repair (65%-100%), or acute MCL reconstruction (81%-100%). Lysholm scores were not different between the strategies. CONCLUSIONS: Outcomes in this systematic review suggest that ACL stabilization in the acute setting might result in the lowest rates of residual valgus laxity, whereas there is no clear difference between the different MCL treatments along with acute ACL reconstruction. Nonoperative MCL treatment with either nonoperative or delayed ACL reconstruction, as well as acute MCL repair with either nonoperative or delayed ACL reconstruction, leads to higher rates of valgus laxity. LEVEL OF EVIDENCE: Level IV, systematic review of Level I to IV studies.

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.

Healing of acute anterior cruciate ligament rupture on MRI and outcomes following non-surgical management with the Cross Bracing Protocol.

OBJECTIVE: Investigate MRI evidence of anterior cruciate ligament (ACL) healing, patient-reported outcomes and knee laxity in patients with acute ACL rupture managed non-surgically with the Cross Bracing Protocol (CBP). METHODS: Eighty consecutive patients within 4 weeks of ACL rupture were managed with CBP (knee immobilisation at 90° flexion in brace for 4 weeks, followed by progressive increases in range-of-motion until brace removal at 12 weeks, and physiotherapist-supervised goal-oriented rehabilitation). MRIs (3 months and 6 months) were graded using the ACL OsteoArthritis Score (ACLOAS) by three radiologists. Mann-Whitney U tests compared Lysholm Scale and ACL quality of life (ACLQOL) scores evaluated at median (IQR) of 12 months (7-16 months) post-injury, and χ2 tests compared knee laxity (3-month Lachman's test and 6-month Pivot-shift test), and return-to-sport at 12 months between groups (ACLOAS grades 0-1 (continuous±thickened ligament and/or high intraligamentous signal) versus ACLOAS grades 2-3 (continuous but thinned/elongated or complete discontinuity)). RESULTS: Participants were aged 26±10 years at injury, 39% were female, 49% had concomitant meniscal injury. At 3 months, 90% (n=72) had evidence of ACL healing (ACLOAS grade 1: 50%; grade 2: 40%; grade 3: 10%). Participants with ACLOAS grade 1 reported better Lysholm Scale (median (IQR): 98 (94-100) vs 94 (85-100)) and ACLQOL (89 (76-96) vs 70 (64-82)) scores, compared with ACLOAS grades 2-3. More participants with ACLOAS grade 1 had normal 3-month knee laxity (100% vs 40%) and returned to pre-injury sport (92% vs 64%), compared with participants with an ACLOAS grades 2-3. Eleven patients (14%) re-injured their ACL. CONCLUSION: After management of acute ACL rupture with the CBP, 90% of patients had evidence of healing on 3-month MRI (continuity of the ACL). More ACL healing on 3-month MRI was associated with better outcomes. Longer-term follow-up and clinical trials are needed to inform clinical practice.

Outpatient-based diagnostic criteria for partial ACL injury: clinical outcomes of non-operative treatment and radiographic predictor.

INTRODUCTION: This study aimed to (1) evaluate the short-term clinical outcomes of patients who underwent non-operative treatment for partial anterior cruciate ligament (ACL) tears diagnosed using the outpatient-based diagnostic criteria and (2) investigate the radiographic predictors distinguishing patients at risk of non-operative treatment failure. METHODS: From 2010 to 2019, patients diagnosed with partial ACL tears and treated with non-operative treatment were reviewed retrospectively. Patients were then classified into two groups: those who successfully responded to non-operative treatment (group S) and those who failed to respond to non-operative treatment and required surgical reconstruction within 6 months after injury (group F). ACL laxity, patient-reported outcomes (PROs), and several radiographic parameters were analyzed. To identify radiographic predictors related to clinical outcomes, radiographic parameters were compared between the groups, which were statistically matched for potential confounders (age and activity level) using inverse probability of treatment weighting. RESULTS: A total of 44 patients were analyzed (mean age, 28.7 ± 8.7 years; 31 men), and classified into two groups (group S, 23 patients; group F, 21 patients). There were no significant differences in ACL laxity and PROs between the groups at 1 year after either non-operative treatment or surgical reconstruction. A comparison of radiographic parameters between the groups revealed significant differences in several parameters related to secondary signs of ACL injury. Subsequent regression analyses revealed that anterior tibial translation and extent of bone bruises were radiographic predictors related to clinical outcomes. CONCLUSION: Non-operative treatment for partial ACL tears diagnosed using the outpatient-based diagnostic criteria can provide successful short-term clinical outcomes in selective patients. Secondary signs of ACL injuries, particularly the amount of anterior tibial translation and the extent of bone bruises, are radiographic predictors that could differentiate patients at risk of non-operative treatment failure. LEVEL OF EVIDENCE: Retrospective cohort study, III.

Efficacy of non-surgical management and functional outcomes of partial ACL tears. A systematic review of randomised trials.

BACKGROUND: The incidence of anterior cruciate ligament (ACL) injuries represents a large burden of knee injuries in both the general and sporting populations, often requiring surgical intervention. Although there is much research on complete ACL tears including outcomes and indications for surgery, little is known about the short- and long-term outcomes of non-operative, physiotherapy led intervention in partial ACL tears. The primary aim of this study was to evaluate studies looking at the effectiveness of physiotherapy led interventions in improving pain and function in young and middle-aged adults with partial ACL tears. Additionally, the secondary aim was to evaluate the completeness of exercise prescription in randomised trials for physiotherapy led interventions in the management in partial ACL tears. METHODS: A comprehensive and systematic search was performed on six databases (Medline, CINAHL, EMBASE, PEDro, Scopus, SPORTDiscus and Cochrane). The search strategy consisted of two main concepts: (i) partial ACL tears, and (ii) non-operative management. 7,587 papers were identified by the search. After screening of eligible articles by two independent reviewers, 2 randomised studies were included for analysis. The same two reviewers assessed the completeness of reporting using the Toigio and Boutellier mechanobiological exercise descriptions and Template for Intervention Description and Replication (TIDieR) checklist. Group mean standard deviations (SD) for the main outcomes was extracted from both papers for analysis. Prospero Registration Number: CRD42020179892. RESULTS: The search strategy identified two studies; one looking at Tai Chi and the other Pilates. The analysis indicated that Tai Chi was significant in reducing pain scores and both Tai Chi and Pilates were found to increase Muscle Peak Torque Strength (MPTS) at 180 degrees. Furthermore, Tai Chi showed a significant increase in proprioception. CONCLUSIONS: Physiotherapy led interventions such as Pilates, and Tai Chi may improve pain, proprioception and strength in young and middle-aged adults with partial ACL tears, however full scale, high-quality randomised studies are required with long term outcomes recorded.

Advanced Gene Therapy Strategies for the Repair of ACL Injuries.

The anterior cruciate ligament (ACL), the principal ligament for stabilization of the knee, is highly predisposed to injury in the human population. As a result of its poor intrinsic healing capacities, surgical intervention is generally necessary to repair ACL lesions, yet the outcomes are never fully satisfactory in terms of long-lasting, complete, and safe repair. Gene therapy, based on the transfer of therapeutic genetic sequences via a gene vector, is a potent tool to durably and adeptly enhance the processes of ACL repair and has been reported for its workability in various experimental models relevant to ACL injuries in vitro, in situ, and in vivo. As critical hurdles to the effective and safe translation of gene therapy for clinical applications still remain, including physiological barriers and host immune responses, biomaterial-guided gene therapy inspired by drug delivery systems has been further developed to protect and improve the classical procedures of gene transfer in the future treatment of ACL injuries in patients, as critically presented here.

Development of MRI-defined Structural Tissue Damage after Anterior Cruciate Ligament Injury over 5 Years: The KANON Study.

Background MRI is used to evaluate structural joint changes after anterior cruciate ligament (ACL) injury, but no long-term data are available for comparing different treatment approaches. Purpose To describe structural joint damage with MRI over a 5-year period in the Knee Anterior Cruciate Ligament, Nonsurgical versus Surgical Treatment (KANON) study and to compare frequencies of such tissue damage for a nonsurgical versus a surgical treatment strategy. Materials and Methods In this secondary analysis of a prospective trial (ISRCTN 84752559), 119 participants with an acute ACL injury were evaluated. Participants were enrolled from 2002 through 2006, the 2-year follow-up started in 2008, and the 5-year follow-up started in 2011. A 1.5-T MRI examination was performed at baseline and at 2- and 5-year follow-up. MRI scans were read according to a validated scoring instrument. Kruskal-Wallis tests were used to assess whether the frequencies of structural damage differed between the three as-treated groups. Results Of 119 participants (mean age, 26 years ± 5 [standard deviation]), 91 men were evaluated. At 2- and 5-year follow-up, respectively, 13% (15 of 117) and 13% (15 of 115) of knees showed incident cartilage damage in the medial tibiofemoral joint, 11% (13 of 117) and 17% (20 of 115) of knees showed incident cartilage damage in the lateral tibiofemoral joint, and 4% (five of 117) and 8% (nine of 115) of knees showed incident cartilage damage in the patellofemoral joint. Osteophyte development was seen in 23% (27 of 117) and 29% (33 of 115) of knees in the medial tibiofemoral joint, in 36% (42 of 117) and 43% (49 of 115) of knees in the lateral tibiofemoral joint, and in 35% (41 of 117) and 37% (42 of 115) of knees in the patellofemoral joint. No major differences between the groups were found for incident or worsening cartilage damage, bone marrow lesions, and osteophytes at 2 or 5 years. The rehabilitation-alone group showed less Hoffa-synovitis at 2 (P = .02) and 5 (P = .008) years. Conclusion Young adults with anterior cruciate ligament injury showed no major difference in frequency of structural tissue damage on MRI scans at 2 and 5 years regardless of treatment. However, the rehabilitation-alone group had less inflammation at 2 and 5 years. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Andreisek in this issue.

Treatment after ACL injury: Panther Symposium ACL Treatment Consensus Group.

Treatment strategies for ACL injuries continue to evolve. Evidence supporting best practice guidelines to manage ACL injury is largely based on studies with low-level evidence. An international consensus group of experts was convened determine consensus regarding best available evidence on operative versus non-operative treatment for ACL injury. The purpose of this study is to report the consensus statements on operative versus non-operative treatment of ACL injuries developed at the ACL Consensus Meeting Panther Symposium 2019. Sixty-six international experts on the management of ACL injuries, representing 18 countries, convened and participated in a process based on the Delphi method of achieving consensus. Proposed consensus statements were drafted by the Scientific Organising Committee and Session Chairs. Panel participants reviewed preliminary statements prior to the meeting and provided initial agreement and comments on the statement via online survey. During the meeting, discussion and debate occurred for each statement, after which a final vote was then held. Eighty per cent agreement was defined a priori as consensus. A total of 11 of 13 statements on operative versus non-operative treatment of ACL injury reached consensus during the Symposium. Nine statements achieved unanimous support, two reached strong consensus, one did not achieve consensus, and one was removed due to redundancy in the information provided. In highly active patients engaged in jumping, cutting and pivoting sports, early anatomical ACL reconstruction is recommended due to the high risk of secondary meniscus and cartilage injuries with delayed surgery, although a period of progressive rehabilitation to resolve impairments and improve neuromuscular function is recommended. For patients who seek to return to straight plane activities, non-operative treatment with structured, progressive rehabilitation is an acceptable treatment option. However, with persistent functional instability, or when episodes of giving way occur, anatomical ACL reconstruction is indicated. The consensus statements derived from international leaders in the field may assist clinicians in deciding between operative and non-operative treatment with patients after an ACL injury Level of evidence: Level V.

The effectiveness of vibration therapy for muscle peak torque and postural control in individuals with anterior cruciate ligament reconstruction: a systematic review and meta-analysis of clinical trials.

OBJECTIVE: This study aimed to review and summarize the existing evidence on the effectiveness of vibration therapy (VT) in comparison with conventional rehabilitation in anterior cruciate ligament (ACL)-reconstructed patients considering muscle peak torque and postural control. METHODS: We searched available online databases for relevant studies published up to February 2020. All randomized clinical trials investigating the effect of VT on quadriceps peak torque, hamstring peak torque, and postural control (closed-eye and open-eye) were included. Overall, 13 clinical trials with a total sample size of 407 participants were included for the meta-analysis. We used the pooled mean difference with random effects model for meta-analyses. We assessed the heterogeneity of the studies using the I2 and Cochran's Q test. Meta-regression analysis was used to assess the source of heterogeneity. RESULTS: We found that VT significantly improved hamstring peak torque [weighted mean difference (WMD) 12.67, 95% CI 4.51-20.83] and quadriceps peak torque (WMD 0.11, 95% CI -0.06 to 0.29). However, subgroup analysis showed a significant increase in mentioned muscles' peak torque in studies employing interventions including both local muscle vibration (LMV) and vibration frequency higher than 100 Hz (WMD 20.84, 95% CI 11.75-29.93). With regard to postural control, we observed a significant improvement only in open-eye mediolateral postural control (WMD 0.26, 95% CI -1.26 to 1.77). CONCLUSION: This study suggests that VT, especially LMV type with vibration frequency higher than 100 Hz, can be effective in rehabilitation of ACL-reconstructed patients. Although improvement in the peak torque of hamstring and quadriceps muscles was seen, there was no significant improvement in postural control, especially closed-eye, in comparison with conventional rehabilitation. LEVEL OF EVIDENCE: 1. HIGHLIGHTS: Vibration therapy can increase hamstring peak torque in individuals with ACL reconstruction. Local muscle vibration type in comparison with whole-body vibration is recommended for ACL-reconstructed patients. Vibration frequency higher than 100 Hz is preferred in ACL-reconstructed rehabilitation.

Molecular and imaging biomarkers of local inflammation at 2 years after anterior cruciate ligament injury do not associate with patient reported outcomes at 5 years.

OBJECTIVE: To estimate the association between molecular or imaging inflammatory biomarkers at 2 years after anterior cruciate ligament (ACL) injury and patient-reported outcomes at 5 years. METHODS: For 116 ACL-injured patients, molecular biomarkers of inflammation (synovial fluid and serum cytokines) and Hoffa- and effusion-synovitis as visualized on magnetic resonance imaging (MRI) were assessed 2 years post-injury. Knee injury and Osteoarthritis Outcome Score (KOOS) and SF-36 were assessed at 2 and 5 years. We used multiple imputation to handle biomarker values that were below the level of detection or missing, and linear regression for statistical analyses. RESULTS: None of the synovial fluid cytokines or imaging biomarkers of inflammation at 2 years were associated with any of the patient-reported outcomes at 5 years. With each log10 unit higher of serum tumor necrosis factor concentration the knee-related quality of life of KOOS was increased (i.e., better outcome) by 35 (95% confidence interval 7 to 63) points. No other serum biomarker measured at 2 years was associated with patient-reported outcome at 5 years. CONCLUSION: Local joint inflammation assessed by biomarkers in synovial fluid and Hoffa- and effusion-synovitis on MRI at 2 years after an ACL injury did not associate with patient-reported outcomes at 5 years. Thus, chronic inflammation in the ACL-injured knee, as reflected by the biomarkers studied here, seems not to be a key determinant for the long-term patient-reported outcomes.

Evidence too weak to guide surgical treatment decisions for anterior cruciate ligament injury: a systematic review of the risk of new meniscal tears after anterior cruciate ligament injury.

OBJECTIVE: To investigate the risk of new meniscal tears after treatment for anterior cruciate ligament (ACL) injury, in children and adults with and without ACL reconstruction. DESIGN: Prognosis systematic review (PROSPERO registration number CRD42016036788). METHODS: We searched Embase, Ovid Medline, Cochrane, CINAHL, SPORTDiscus, PEDro and Google Scholar from inception to 3rd May 2018. Eligible articles included patients with ACL injury (diagnosis confirmed by MRI and/or diagnostic arthroscopy), reported the number of meniscal tears at the time of ACL injury diagnosis/start of treatment and reported the number of new meniscal tears that subsequently occurred. Articles with fewer than 20 patients at follow-up, and articles limited to ACL revision surgery or multi-ligament knee injuries were excluded. Two independent reviewers screened articles, assessed eligibility, assessed risk of bias and extracted data. We judged the certainty of evidence using the Grading of Recommendations Assessment Development and Evaluation (GRADE) working group methodology. RESULTS: Of 75 studies included in the systematic review, 54 studies with 9624 patients and 501 new meniscal tears were appropriate for quantitative analysis. Heterogeneity precluded data pooling. The risk of new meniscal tears was 0%-21% when follow-up was <2 years, 0%-29% when follow-up was 2 to 5 years, 5%-52% when follow-up was 5 to 10 years and 4%-31% when follow-up was longer than 10 years. The proportion of studies with high risk of selection, misclassification and detection bias was 84%, 69% and 68%, respectively. Certainty of evidence was very low. CONCLUSION: New meniscal tears occurred in 0%-52% of patients between 4 months and 20 years (mean 4.9±4.4 years) following treatment for ACL injury. The certainty of evidence was too low to guide surgical treatment decisions. This review cannot conclude that the incidence of new meniscal tears is lower if ACL injury is treated with surgery compared with treatment with rehabilitation only.

Does surgery reduce knee osteoarthritis, meniscal injury and subsequent complications compared with non-surgery after ACL rupture with at least 10 years follow-up? A systematic review and meta-analysis.

OBJECTIVE: We compared long-term follow-up from surgical versus non-surgical treatment of ACL rupture regarding radiographic knee osteoarthritis (OA), secondary surgery, laxity and patient-reported outcome measures (PROMs). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, MEDLINE, CINAHL and the Cochrane Library databases. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies directly comparing the minimally invasive surgical (arthroscopy or miniarthrotomy) and non-surgical treatment of ACL rupture with at least 10 years of follow-up in adult patients were included. RESULTS: Five studies met the eligibility criteria. A meta-analysis revealed a higher risk of radiographic knee OA and a lower risk of secondary meniscal surgery for patients in the surgical group. The risk of graft rupture/secondary ACL revision and secondary ACL reconstruction was equal in the surgical and non-surgical groups. Knee laxity was lower among patients in the surgical group in four studies. No difference was found in the PROMs (ie, International Knee Documentation Committee, Tegner, Knee Injury and Osteoarthritis Outcome, and Lysholm scores). CONCLUSION: The risk of radiographic knee OA was higher, but the risk of secondary meniscal injury was lower 10 years after surgical treatment of ACL rupture. The risk of graft rupture/secondary ACL revision or secondary reconstruction was unrelated to treatment type. The degree of knee laxity was reduced after surgical treatment in comparison with non-surgical treatment, while PROMs were similar. However, due to the methodological challenges highlighted in this systematic review, these findings must be interpreted with caution. PROSPERO REGISTRATION NUMBER: CRD42019119468.

Treatment after anterior cruciate ligament injury: Panther Symposium ACL Treatment Consensus Group.

Treatment strategies for anterior cruciate ligament (ACL) injuries continue to evolve. Evidence supporting best practice guidelines for the management of ACL injury is to a large extent based on studies with low-level evidence. An international consensus group of experts was convened to collaboratively advance toward consensus opinions regarding the best available evidence on operative vs. non-operative treatment for ACL injury. The purpose of this study is to report the consensus statements on operative vs. non-operative treatment of ACL injuries developed at the ACL Consensus Meeting Panther Symposium 2019. Sixty-six international experts on the management of ACL injuries, representing 18 countries, were convened and participated in a process based on the Delphi method of achieving consensus. Proposed consensus statements were drafted by the Scientific Organizing Committee and Session Chairs for the three working groups. Panel participants reviewed preliminary statements prior to the meeting and provided the initial agreement and comments on the statement via an online survey. During the meeting, discussion and debate occurred for each statement, after which a final vote was then held. Eighty percent agreement was defined a-priori as consensus. A total of 11 of 13 statements on operative v. non-operative treatment of ACL injury reached the consensus during the Symposium. Nine statements achieved unanimous support, two reached strong consensus, one did not achieve consensus, and one was removed due to redundancy in the information provided. In highly active patients engaged in jumping, cutting, and pivoting sports, early anatomic ACL reconstruction is recommended due to the high risk of secondary meniscus and cartilage injuries with delayed surgery, although a period of progressive rehabilitation to resolve impairments and improve neuromuscular function is recommended. For patients who seek to return to straight plane activities, non-operative treatment with structured, progressive rehabilitation is an acceptable treatment option. However, with persistent functional instability, or when episodes of giving way occur, anatomic ACL reconstruction is indicated. The consensus statements derived from international leaders in the field will assist clinicians in deciding between operative and non-operative treatments with patients after an ACL injury.Level of evidence V.

Japanese Orthopaedic Association (JOA) clinical practice guidelines on the management of anterior cruciate ligament injury - Secondary publication.

BACKGROUND: This clinical guideline presents recommendations for the management of patients with anterior cruciate ligament (ACL) injury, endorsed by the Japanese Orthopaedic Association (JOA) and Japanese Orthopaedic Society of Knee, Arthroscopy and Sports Medicine (JOSKAS). METHODS: The JOA ACL guideline committee revised the previous guideline based on "Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014", which proposed a desirable method for preparing clinical guidelines in Japan. Furthermore, the importance of "the balance of benefit and harm" was also emphasized. This guideline consists of 21 clinical questions (CQ) and 23 background questions (BQ). For each CQ, outcomes from the literature were collected and evaluated systematically according to the adopted study design. RESULTS: We evaluated the objectives and results of each study in order to make a decision on the level of evidence so as to integrate the results with our recommendations for each CQ. For BQ, the guideline committee proposed recommendations based on the literature. CONCLUSIONS: This guideline is intended to be used by physicians, orthopedic surgeons, physical therapists, and athletic trainers managing ACL injuries. We hope that this guideline is useful for appropriate decision-making and improved management of ACL injuries.

Enhanced Growth of Lapine Anterior Cruciate Ligament-Derived Fibroblasts on Scaffolds Embroidered from Poly(l-lactide-co-ε-caprolactone) and Polylactic Acid Threads Functionalized by Fluorination and Hexamethylene Diisocyanate Cross-Linked Collagen Foams.

Reconstruction of ruptured anterior cruciate ligaments (ACLs) is limited by the availability and donor site morbidity of autografts. Hence, a tissue engineered graft could present an alternative in the future. This study was undertaken to determine the performance of lapine (L) ACL-derived fibroblasts on embroidered poly(l-lactide-co-ε-caprolactone) (P(LA-CL)) and polylactic acid (PLA) scaffolds in regard to a tissue engineering approach for ACL reconstruction. Surface modifications of P(LA-CL)/PLA by gas-phase fluorination and cross-linking of a collagen foam using either ethylcarbodiimide (EDC) or hexamethylene diisocyanate (HMDI) were tested regarding their influence on cell adhesion, growth and gene expression. The experiments were performed using embroidered P(LA-CL)/PLA scaffolds that were seeded dynamically or statically with LACL-derived fibroblasts. Scaffold cytocompatibility, cell survival, numbers, metabolic activity, ultrastructure and sulfated glycosaminoglycan (sGAG) synthesis were evaluated. Quantitative real-time polymerase chain reaction (QPCR) revealed gene expression of collagen type I (COL1A1), decorin (DCN), tenascin C (TNC), Mohawk (MKX) and tenomodulin (TNMD). All tested scaffolds were highly cytocompatible. A significantly higher cellularity and larger scaffold surface areas colonized by cells were detected in HMDI cross-linked and fluorinated scaffolds compared to those cross-linked with EDC or without any functionalization. By contrast, sGAG synthesis was higher in controls. Despite the fact that the significance level was not reached, gene expressions of ligament extracellular matrix components and differentiation markers were generally higher in fluorinated scaffolds with cross-linked collagen foams. LACL-derived fibroblasts maintained their differentiated phenotype on fluorinated scaffolds supplemented with a HMDI cross-linked collagen foam, making them a promising tool for ACL tissue engineering.

The Effectiveness of Nonoperative Treatment for Anterior Cruciate Ligament Rupture on Patient-Reported Outcomes and Muscular Strength: A Critically Appraised Topic.

Clinical Scenario: Anterior cruciate ligament (ACL) ruptures are one of the most common injuries in young athletic populations. The leading treatment for these injuries is ACL reconstruction (ACL-r); however, nonoperative treatments are also utilized. Following ACL-r, patients experience prolonged muscle weakness and atrophy of the quadriceps muscle group, regardless of rehabilitation. Nonoperative treatment plans following ACL injury exist, but their outcomes are less familiar, in spite of providing insight as a nonsurgical "control" for postsurgical rehabilitation outcomes. Therefore, the purpose of this critically appraised topic was to evaluate quadriceps strength and function following nonoperative ACL rehabilitation using objective and subjective measures including isokinetic dynamometry, the single-leg hop test, and the International Knee Documentation Committee (IKDC) subjective knee form. Focused Clinical Question: What are the effects of nonoperative treatment on peak isokinetic knee-extensor torque, the single-leg hop tests, and the IKDC in patients who have sustained an ACL rupture? Summary of Key Findings: Patients who underwent nonsurgical ACL treatment produced limb symmetry index, with the side-to-side torque difference expressed as a percentage, and values at or above 90% for all 4 single-leg hop tests and strength tests similar to ACL-r patients. All studies showed individuals had higher IKDC scores at baseline collection when compared with patients who underwent ACL-r but showed lower IKDC scores at long-term follow-up compared with ACL-r patients. Clinical Bottom Line: Nonoperative treatments of ACL injuries yield similar long-term results in quadriceps strength as ACL-r. Due to the quality of evidence and the absence of randomized controlled trials on this topic, these outcomes should be considered with caution. Strength of Recommendation: The Oxford Centre for Evidence-Based Medicine taxonomy recommends a grade of B for level 2 evidence with consistent findings.

Silk enhances the ligamentization of the polyethylene terephthalate artificial ligament in a canine anterior cruciate ligament reconstruction model.

Anterior cruciate ligament (ACL) reconstruction is the leading treatment for ACL rupture. Ligament Advanced Reinforcement System (LARS), which is made of polyethylene terephthalate (PET), is the most frequently used artificial ligament for ACL reconstruction. However, PET is hydrophobic, so it is difficult to induce the ingrowth of the autologous tissue. The aim of this study is to explore the effects of silk hybrid on the ligamentization of the PET artificial ligament in a canine ACL reconstruction model. Silk/PET hybrid suspensory ligament was fabricated with silk in the weft yarn and PET in the warp yarn, while PET suspensory ligament was fabricated with PET in both the weft and warp yarns. After fabrication, the micromorphology of the ligaments was observed and mechanical testing was performed. Though the failure loads of the degummed silk/PET hybrid suspensory ligaments were significantly lower than those of the PET suspensory ligaments (P < 0.001), both of them were enough for ACL reconstructions of beagle dogs. In the animal study, 14 beagle dogs were divided into PET suspensory ligament group and silk/PET hybrid suspensory ligament group randomly, with 7 dogs in each. The dogs underwent ACL reconstructions in their right knees. At postoperative 6 months, the dogs were sacrificed, and the specimens were evaluated with gross observation, histology, immunohistochemistry, and mechanical testing. The histological and immunohistochemical results showed that the native ACL of the beagle dog held abundant fibroblasts and collagen. The PET-regenerated ligament was loose, and there was a small amount of autologous tissue and collagen. Compared to the PET-regenerated ligament, the silk/PET hybrid-regenerated ligament had a compact structure, and there was more regenerated autologous tissue and collagen. In conclusion, compared to the PET ligament, the silk/PET hybrid ligament kept greater ability to induce the ingrowth of the autologous tissue, indicating that the silk hybrid had enhanced the ligamentization of the PET artificial ligament.

Silicate-substituted strontium apatite nano coating improves osteogenesis around artificial ligament.

BACKGROUND: Treatment of anterior cruciate ligament injuries commonly involves the use of polyethylene terephthalate (PET) artificial ligaments for reconstruction. However, the currently available methods require long fixation periods, thereby necessitating the development of alternative methods to accelerate the healing process between tendons and bones. Thus, we developed and evaluated a novel technique that utilizes silicate-substituted strontium (SrSiP). METHODS: PET films, nano-coated with SrSiP, were prepared. Bone marrow mesenchymal cells (BMSCs) from femurs of male rats were cultured and seeded at a density of 1.0 × 104/cm2 onto the SrSiP-coated and non-coated PET film, and subsequently placed in an osteogenic medium. The osteocalcin concentration secreted into the medium was compared in each case. Next, PET artificial ligament, nano-coated with SrSiP, were prepared. BMSCs were seeded at a density of 4.5 × 105/cm2 onto the SrSiP-coated, and non-coated artificial ligament, and then placed in osteogenic medium. The osteocalcin and calcium concentrations in the culture medium were measured on the 8th, 10th, 12th, and 14th day of culture. Furthermore, mRNA expression of osteocalcin, alkaline phosphatase (ALP), bone morphogenetic protein-2 (BMP2), and runt-related transcription factor 2 (Runx2) was evaluated by qPCR. We transplanted the SrSiP-coated and non-coated artificial ligament to the tibiae of mature New Zealand white rabbits. Two months later, we sacrificed them and histologically evaluated them. RESULTS: The secretory osteocalcin concentration in the medium on the film was significantly higher for the SrSiP group than for the non-coated group. Secretory osteocalcin concentration in the medium on the artificial ligament was also significantly higher in the SrSiP group than in the non-coated group on the 14th day. Calcium concentration on the artificial ligament was significantly lower in the SrSiP group than in the non-coated group on the 8th, 10th, 12th, and 14th day. In qPCR as well, OC, ALP, BMP2, and Runx2 mRNA expression were significantly higher in the SrSiP group than in the non-coated group. Newly formed bone was histologically found around the artificial ligament in the SrSiP group. CONCLUSIONS: Our findings demonstrate that artificial ligaments using SrSiP display high osteogenic potential and thus may be efficiently used in future clinical applications.

It is good to feel better, but better to feel good: whether a patient finds treatment 'successful' or not depends on the questions researchers ask.

INTRODUCTION: In sports physiotherapy, medicine and orthopaedic randomised controlled trials (RCT), the investigators (and readers) focus on the difference between groups in change scores from baseline to follow-up. Mean score changes are difficult to interpret ('is an improvement of 20 units good?'), and follow-up scores may be more meaningful. We investigated how applying three different responder criteria to change and follow-up scores would affect the 'outcome' of RCTs. Responder criteria refers to participants' perceptions of how the intervention affected them. METHODS: We applied three different criteria-minimal important change (MIC), patient acceptable symptom state (PASS) and treatment failure (TF)-to the aggregate Knee injury and Osteoarthritis Outcome Score (KOOS4) and the five KOOS subscales, the primary and secondary outcomes of the KANON trial (ISRCTN84752559). This trial included young active adults with an acute ACL injury and compared two treatment strategies: exercise therapy plus early reconstructive surgery, and exercise therapy plus delayed reconstructive surgery, if needed. RESULTS: MIC: At 2 years, more than 90% in the two treatment arms reported themselves to be minimally but importantly improved for the primary outcome KOOS4. PASS: About 50% of participants in both treatment arms reported their KOOS4 follow-up scores to be satisfactory. TF: Almost 10% of participants in both treatment arms found their outcomes so unsatisfactory that they thought their treatment had failed. There were no statistically significant or meaningful differences between treatment arms using these criteria. CONCLUSION: We applied change criteria as well as cross-sectional follow-up criteria to interpret trial outcomes with more clinical focus. We suggest researchers apply MIC, PASS and TF thresholds to enhance interpretation of KOOS and other patient-reported scores. The findings from this study can improve shared decision-making processes for people with an acute ACL injury.