Four-Strand Hamstring Tendo Autograft For Anterior Cruciate Ligament Reconstruction: A Meta-Analysis Of The Effectivity And Safety

BackgroundAnterior cruciate ligament (ACL) injury is a common and serious sports injury, with the highest incidence seen in teenagers or young adults playing multi-directional sports. These sports are skiing, wrestling, football, judo, gymnastics and other athletes. Recently, the incidence is markedly increased in the general population. Anterior cruciate ligament is a very tough fiber bundle. It is an important knee joint stability structure with other ligaments around the knee joint to maintain the normal tibiofemoral joint motion. Its main functions are:to prevent the tibia to move forward in the course of knee flexion, to prevent hyperextension when the knee extenson; to control the knee rotation; to reduce the knee varus or valgus when the knee at different angles, to involve in the "lock" movement of end-stage of knee extension.The clinical manifestations of anterior cruciate ligament injury are activity limitation, pain and knee laxity. Pivo-shift test, Lachman test, anterior drawer test and other examinations are meaningful. Because of its high sensitivity and specificity, MRI is considered to be the gold standard. Its diagnostic accuracy is 93%. Arthroscopy as a minimally invasive examination for accurate diagnosis of ACL injury is significant.Anterior cruciate ligament injury easily lead to knee instability, and gradually rise to the secondary injury of articular cartilage and other structures within the joint, resulting in the occurrence of traumatic arthritis, seriously affecting the daily life and motor function. It should be actively treated.Treatment options of anterior cruciate ligament injury include non-surgical treatment, surgical suture, extra-articular surgical approach and reconstruction using various materials grafting. Because the healing of anterior cruciate ligament is difficult, the efficacy of non-surgical method, direct suture of intra-articular and articular reconstruction of static or dynamic effect is not ideal. The various applications of graft materials for anterior cruciate ligament reconstruction can quickly restore knee joints stability and motor cordination, especially arthroscopic mature technology and extensive application of this technology show a clear advantage.There is a variety of specific surgical changes of anterior cruciate ligament reconstruction. For example, the choice of graft, femoral and tibial graft tunnel position, double bundle or single bundle and graft fixation.The primary issue of anterior cruciate ligament reconstruction is the choice of graft material. Currently, there are many types of graft, including autograft, allograft and synthetic graft. Autograft include hamstring tendon autograft, patellar tendon autograft, quadriceps tendon autograft and so on. Although allografts (allograft tendon) and artificial ligament have their advantages, there are obvious shortcomings. Autograft, in particular, patellar tendon autograft for anterior cruciate ligament reconstruction is the gold standard, but may lead to anterior knee pain, kneeling pain, patellar fracture, patellar ligament tear and other complications. In recent years, hamstring tendon autograft increased significantly. Hamstring tendon autograft has gone through the evolution from 1 strand to 4 or even 6 to 8 strands. In particular, 4-strand hamstring tendon autograft is more commonly used at present. Although the hamstring tendon has ideal strength and fewer complications for donor site, the contacts of both ends is in the form of soft tissue and bone, resulting in longer healing time and bone tunnel widening after reconstruction. Whether 4-strand hamstring tendon autograft is superior to patellar tendon autograft needs further study.Another important issue of anterior cruciate ligament reconstruction is the choice of double bundle or single bundle. The anterior vertical stability of the knee recovered well with single bundle reconstruction of ACL. However, due to reconstruction of the anteromedial bundle only, this can not recover the kinetics of the normal knee and can not properly control the rotation load. With further research, anatomic double-bundle reconstruction of the anterior cruciate ligament closer to its anatomical structure and biomechanical characteristics, it can restore the anatomical location of anteromedial bundle and posterolateral bundle in the femur and tibia, restore the anterior vertical stability and better rotational stability. However, there is still much controversy whether knee stability and function scores of anatomic double-bundle and double tunnel reconstruction are better than single-bundle reconstruction. It is worth further study.In this paper, we will evaluate the efficacy and safety of patellar tendon autograft compare with 4-strand hamstring tendon autograft, and double-bundle compare with single-bundle of 4-strand hamstring tendon autograft for anterior cruciate ligament reconstruction-with Meta analysis.Objective1. To evaluate the efficacy of patellar tendon autograft and 4-strand hamstring tendon autograft for anterior cruciate ligament reconstruction. 2. To evaluate the safety of patellar tendon autograft and 4-strand hamstring tendon autograft for anterior cruciate ligament reconstruction.3. To evaluate the efficacy of double-bundle comparing with single-bundle of 4-strand hamstring tendon autograft for anterior cruciate ligament reconstruction.Methods1. According to the research purposes, an appropriate detailed inclusion and exclusion criteria (including the type of research, study characteristics, interventions, and outcomes measurement) was developed. With the development of these standards, a systematic and comprehensive search strategy was drawn up. the chosen design type of literature were randomized controlled trials (RCTs), limited to English and Chinese.2. Cochrane Library, PubMed, Embase and Chinese Biomedical Literature Databases were searched. The references of the relevant literature and major Chinese journal of orthopedics (the part is not included by the databases) were manually retrieved. Collected and screened the RCTs that met the inclusion and exclusion criteria.These articles included patellar tendon autograft and 4-strand hamstring tendon autograft, double-bundle and single-bundle grafting of 4-strand hamstring tendon for ACL reconstruction.3. The Cochrane Collaboration’s tool for assessing risk of bias (in Cochrane Reviewer Handbook 5.0.2) was used. It is the recommended approach for assessing risk of bias in studies included. It includes six aspects of sequence generation, allocation concealment, blinding of participants or personnel and blinding of outcome assessment, incomplete outcome data, selective outcome reporting and’other issues’ (Subdivided into two aspects:comparable baseline, and fund support). Within each entry, the first part of the tool describes what was reported to have happened in the study, in sufficient detail to support a judgement about the risk of bias. The second part of the tool assigns a judgement relating to the risk of bias for that entry. This is achieved by assigning a judgement of ’low risk’ of bias,’high risk’ of bias, or ’unclear risk’ of bias. Meanwhile, funnel plot was given of the outcomes analysis from 5 or more study in order to analyze the publication bias.4. After strict quality evaluation of the included study, data extraction was conducted. According to the clinical heterogeneity, the data may be divided into three subgroups:follow-up 2 to 3 years,5 years and 10 years. Such a meta-analysis yields an overall statistic (together with its confidence interval) that summarizes the effectiveness of the experimental intervention compared with a control intervention. The RevMan5.0 provided by the Cochrane Collaboration was used for Meta-analysis. The effect measure used in our study with dichotomous data was the risk ratio (RR). The summary statistics was used for meta-analysis of continuous data:the standardized mean difference (SMD). Both show 95% confidence interval (confidence interval, CI). First clinical heterogeneity was analyzed. If there was a clinical heterogeneity, subgroup analysis was conducted; if not, chi-square test was used to test statistical heterogeneity between studies, the level ofα=0.1 for the test, while using I2 to quantify the size of the heterogeneity. The combination of intervention effect estimates across studies may optionally incorporate an assumption that the studies are not all estimating the same intervention effect, but estimate intervention effects that follow a distribution across studies. This is the basis of a random-effects meta-analysis. Alternatively, if it is assumed that each study is estimating exactly the same quantity a fixed-effect meta-analysis is performed. If the measure can not be quantitative synthesis or extremely low incidence of events, qualitative evaluation was implemented. A sensitivity analysis is a repeat of the primary analysis or meta-analysis, substituting alternative decisions or ranges of values for decisions that were arbitrary or unclear. Finally, sensitivity analysis was implemented. The other tests included in the study with different test characteristics were excluded to study its impact on the results. These features include the quality of research methodology, the weight of the study and the clinical characteristics of participants. That is to say, this study’s sensitivity analysis was whether the result is the same with the original Meta analysis after removing the different quality studies or large weight study. If the results were consistent, indicating that the conclusion was reliable.5. GRADE (Grades of Recommendation, Assessment, Development and Evaluation) was used in the assessment of levels of evidence and strength of recommendations. RCT quality will be degraded in 5 cases:study limitations, inconsistency of results, indirectness of evidence, imprecision, publication bias. The GRADE system classifies the quality of evidence in one of four grades:moderate, low, very low; recommendations in one of two grades:strong recommendation and weak recommendation.ResultsPatellar tendon autograft and 4-strand hamstring tendon autograft for anterior cruciate ligament reconstruction:1. No significant differences were found between the two groups regarding KT-1000 or KT2000 arthrometer side-to-side differences in anterior knee laxity at 134 N,<3mm [RR=0.96,95%CI (0.75,1.22), P=0.73],3～5mm [RR=0.75, 95%CI(0.52,1.08), P=0.12]、>5mm[RR=1.86,95%CI (0.31,2.37), P=0.77]. There is a study in 10-year follow-up subgroup, the results showed no statistically significant (P= 0.727).2. No significant differences were found between the two groups regarding Pivot-shift test,0, [RR=1.05,95%CI (0.97,1.14), P=0.22];+1, [RR=0.90, 95%CI (0.64,1.26), P=0.54];+2, [RR=0.33,95%CI (0.10,1.10), P=0.07] 3. No significant differences were found between the two groups regarding Lachman test,0,[RR=1.04,95%CI (0.91,1.18), P=0.58];+1,[RR=0.94,95%CI (0.69,1.27), P=0.69];+2, [RR=0.42,95%CI (0.11,1.59), P=0.20]4. No significant differences were found between the two groups regarding graft failure rate [RR=0.71,95%CI (0.39,1.31), P=0.28]. There was a study report no significant difference in 10-year follow-up subgroup.5. No significant differences were found between the two groups regarding extension deficit (degrees) in two subgroups:extension deficit (degrees)<3°and≥5°, mean 2～3 and 5 years follow-up. There was a significant difference between the two groups regarding 3～5°of extension deficit (degrees) after 2～3 years [RR=1.94, 95%CI (1.14,3.30), P=0.01]; no significant difference after 5 years follow-up; and significant difference regarding analysis of data consolidation [RR=1.62,95%CI (1.00,2.62), P=0.05].6. No significant difference was found between the two groups regarding≥6°of flexion deficit (degrees), mean 2-3 years follow-up. There was a significant difference after 5 years follow-up [RR=3.57,95%CI (1.19,10.71), P=0.02] and no significant difference regarding analysis of data consolidation.7. There was a significant difference between the two groups regarding anterior knee pain, mean 2-3 years follow-up [RR=2.04,95%CI (1.34,3.09), P=0.0008]; and no significant difference after 5 years follow-up; and a significant difference regarding analysis of data consolidation[RR=2.14,95%CI (1.44,3.17), P=0.0002]. There was a study report no significant difference in 10-year follow-up subgroup.8. There was a significant difference between the two groups regarding kneeling pain or discomfort, mean 2～3 years follow-up [RR=1.78,95%CI (1.12,2.83), P =0.01]; and no significant difference after 5 years follow-up; and a significant difference regarding analysis of data consolidation [RR=1.97,95%CI (1.01,3.85), P=0.05]. There was a study report no significant difference in 10-year follow-up subgroup.9. No significant differences were found between the two groups regarding walking pain, mean 2～3 and 5 years follow-up. There was a study report no significant difference in 10-year follow-up subgroup.10. No significant differences were found between the two groups in terms of IKDC score (normal and near normal, A+B), mean 2～3,5 years follow-up.11. No significant differences were found between the two groups in terms of Lysholm score (excellent+good), mean 2～3,5 years follow-up.12. Assessing risk of bias of the included study:high risk of bias (6 articles), moderate risk of bias (8 articles).13. Quality of evidence and strength of recommendations. A few evidence were moderate (pivot-shift test after the merger between subgroups, graft failure rate of 2 to 3 years follow-up subgroup and subgroup after the merger of IKDC objective score). The majority evidence were very low of the follow-up subgroup, majority were low after the merger between subgroups. Recommendation was strong.Double bundle and single bundle of 4-strand hamstring tendon autograft for anterior cruciate ligament reconstruction:1. There was a significant difference between the double bundle and single bundle regarding KT2000 or KT1000 measurements reported in the form of a continuous variable[SMD=-0.27,95%CI (-0.53,-0.01), P=0.04]. NO significant differences were found in terms of side to side difference<3mm [RR=1.15,95%CI (0.96,1.38), P=0.14] and 3～5mm [RR=1.15,95%CI (0.96,1.38), P=0.14] of KT2000 or KT1000 measurements reported in the form of a categorical variables. There was a significant difference between the double bundle and single bundle regarding side to side difference>5mm of KT2000 or KT1000 measurements reported in the form of a categorical variables [RR=0.18,95%CI (0.04,0.79), P= 0.05].2. Significant differences were found between the two groups regarding Pivot-shift test,0, [RR=1.35,95%CI (1.16,1.56), P<0.0001];+1, [RR=0.37, 95%CI (0.18,0.74), P=0.005];+2, [RR=0.17,95%CI (0.06,0.66), P=0.01].3. Significant differences were found between the two groups in terms of Lachman test:grade 0 [RR=1.28,95%CI (1.12,1.46), P=0.0004] and grade+2 [RR =0.10,95%CI (0.01,0.74), P=0.02]; No difference was found in terms of grade+1 of Lachman test [RR=0.72,95%CI (0.36,1.43), P=0.34].4. No significant difference was found between the two groups in terms of IKDC subjective score [SMD= 0.03,95%CI (-0.21,0.28), P=0.79]; A significant difference was found between the two groups in terms of IKDC objective score (normal and near normal, A+B) [RR=1.07,95%CI (1.01,1.13),P=0.02].5. No significant difference was found between the two groups in terms of Lysholm score [SMD=-0.25,95%CI (-0.53,0.02), P=0.07].6. Assessing risk of bias of the included study. There was the possibility of high or moderate risk of bias.7. Quality of evidence and strength of recommendations. A few evidence were moderate (subgroup after the merger of IKDC objective score, A+B). All evidence were very low of the follow-up subgroup, majority were low after the merger between subgroups.. Recommendation was weak.Conclusions1. Patellar tendon autograft and 4-strand hamstring tendon autograft,both grafts are equivalent option for anterior cruciate ligament reconstruction.2. There is no difference in terms of the graft failure. In the patellar tendon group, there are higher prevalence of postoperative extension deficit (degrees) and flexion deficit (degrees), anterior knee pain and kneeling discomfort. With the follow-up time, the result of the two groups is no different.3. Double-bundle anatomical anterior cruciate ligament reconstruction using 4-strand hamstring tendon autograft is better than single-bundle reconstruction, in terms of the anterior vertical stability and rotational stability. However, there is no difference in terms of the IKDC subjective score and Lysholm score.4. Because of the possibility of various biases in the included study, the level of evidence of this Meta-analysis is not high. Still need more research, especially to pay attention to study design, such as random sequence generation and allocation concealment, blinding of participants and personnel and blinding of outcome assessment, a perfect follow-up and complete report of test results.5. Compared with patellar tendon autograft,4-strand hamstring tendon autograft for ACL reconstruction is recommended. The grade is strong recommendation.6. Compared with the single-bundle reconstruction, double-bundle anatomical anterior cruciate ligament reconstruction using 4-strand hamstring tendon autograft is recommended. The grade is weak recommendation.