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Genetic Variants and Anterior Cruciate Ligament Rupture: A Systematic Review.

ABSTRACT: Studies have shown a familial predisposition for anterior cruciate ligament (ACL) rupture and have been followed by genetic-association studies on polymorphisms in candidate genes in recent years. To date, no systematic review with a best-evidence synthesis has evaluated the influence of genetics on this devastating knee injury.Our objective was to evaluate the association between genetic variants and ACL rupture.We performed an extensive search in Embase, MEDLINE, Web of Science, Scopus, PubMed Publisher, Cochrane Register of Clinical Trials, and Google scholar up to 24 August 2015. Studies were eligible if they met the following inclusion criteria: (1) design was a case-control study, retrospective or prospective follow-up study, or a randomized controlled trial (RCT); (2) the study examined the association between a genetic variant and ACL rupture in both an ACL and a control group. We determined the risk of bias for all included studies.We included a total of 16 studies (eight at high risk of bias and eight with an unclear risk) that examined 33 different DNA variants. Conflicting evidence was found for the COL1A1 rs1800012 and COL3A1 rs1800255 variants, whereas limited evidence was found for no association of the COL5A1 rs12722 and rs13946 and COL12A1 rs970547 variants (all encoding collagen). Evidence was insufficient to draw conclusions as to whether any other genetic variant identified in this review had any association with ACL rupture.More research is needed to support a clear association between ACL rupture and genetic variants. Genome-wide studies are recommended for exploring more potential genetic variants. Moreover, large prospective studies are needed to draw robust conclusions.

SUBMITTER: Kaynak M

PROVIDER: S-EPMC5507974 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Genetic Variants and Anterior Cruciate Ligament Rupture: A Systematic Review.

Kaynak Mustafa M Nijman Frank F van Meurs Joyce J Reijman Max M Meuffels Duncan E DE

Sports medicine (Auckland, N.Z.) 20170801 8

<h4>Background</h4>Studies have shown a familial predisposition for anterior cruciate ligament (ACL) rupture and have been followed by genetic-association studies on polymorphisms in candidate genes in recent years. To date, no systematic review with a best-evidence synthesis has evaluated the influence of genetics on this devastating knee injury.<h4>Objective</h4>Our objective was to evaluate the association between genetic variants and ACL rupture.<h4>Methods</h4>We performed an extensive sear ...[more]

PMID: 28102489

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Project description:BackgroundRevision anterior cruciate ligament (ACL) reconstruction is believed to have an inferior outcome compared with primary ACL reconstruction. The available literature on the outcome of revision ACL reconstruction is sparse compared with that for primary reconstruction. The purpose of this systematic review was to test the hypothesis that the outcome of revision ACL reconstruction compares unfavorably with the historical outcome of primary ACL reconstruction.MethodsA systematic review of studies evaluating the outcome of revision ACL reconstructions with a minimum of two years of follow-up was performed. Pooled data were collected when appropriate and a mixed-effect-model meta-analysis was performed for important outcome measures that were reported in several studies (objective graft failure, Lysholm score, International Knee Documentation Committee [IKDC] subjective score, and IKDC objective score). Objective failure was defined as repeat revision, a side-to-side difference of >5 mm measured with use of a KT1000 arthrometer, or a pivot-shift grade of 2+ or 3+.ResultsTwenty-one studies were included, and 863 of the 1004 patients in these studies had a minimum of two years of follow-up and were analyzed. The pooled mean age of the patients at the time of the revision procedure was 30.6 years, and 66% were male. Objective failure occurred in 13.7% ± 2.7% of the patients (95% confidence interval, 8.0% to 19.4%). The mean Lysholm score in 491 patients was 82.1 ± 3.3 (95% confidence interval, 74.6 to 89.5) according to a mixed-model meta-analysis. The mean IKDC subjective score in 202 patients was 74.8 ± 4.4 (95% confidence interval, 62.5 to 87.0).ConclusionsRevision ACL reconstruction resulted in a worse outcome compared with primary ACL reconstruction. Patient-reported outcome scores were inferior to previously published results of primary ACL reconstruction, but these differences may not be clinically important. A dramatically elevated failure rate was noted after revision ACL reconstruction; this rate was nearly three to four times the failure rate in prospective series of primary ACL reconstructions.

Project description:BackgroundInjury to the anterior cruciate ligament (ACL) of the knee is common. Following complete rupture of the ACL, insufficient re-vascularization of the ligament prevents it from healing completely, creating a need for reconstruction. A variety of grafts are available for use in ACL reconstruction surgery, including synthetic grafts. Over the last two decades new types of synthetic ligaments have been developed. One of these synthetic ligaments, the Ligament Advanced Reinforcement System (LARS), has recently gained popularity.The aim of this systematic review was to assess the current best available evidence for the effectiveness of the LARS as a surgical option for symptomatic, anterior cruciate ligament rupture in terms of graft stability, rehabilitation time and return to pre-injury function.MethodThis systematic review included studies using subjects with symptomatic, ACL ruptures undergoing LARS reconstruction. A range of electronic databases were searched in May 2010. The methodological quality of studies was appraised with a modified version of the Law critical appraisal tool. Data relating to study characteristics, surgical times, complication rates, outcomes related to knee stability, quality of life, function, and return to sport as well as details of rehabilitation programs and timeframes were collected.ResultsThis review identified four studies of various designs, of a moderate methodological quality. Only one case of knee synovitis was reported. Patient satisfaction with LARS was high. Graft stability outcomes were found to be inconsistent both at post operative and at follow up periods. The time frames of rehabilitation periods were poorly reported and at times omitted. Return to pre-injury function and activity was often discussed but not reported in results.ConclusionsThere is an emerging body of evidence for LARS with comparable complication rates to traditional surgical techniques, and high patient satisfaction scores. However, this systematic review has highlighted several important gaps in the existing literature that require future prospective investigation. The findings of this review were equivocal with regards to other measures such as graft stability and long term functional outcomes. While the importance of rehabilitation following LARS is well recognised, there is limited evidence to guide rehabilitation protocols.

Project description:BackgroundAnterior cruciate ligament (ACL) graft rupture occurs at a high rate, especially in young athletes. The geometries of the tibial plateau and femoral intercondylar notch are risk factors for first-time ACL injury; however, little is known about the relationship between these geometries and risk of ACL graft rupture.HypothesisThe geometric risk factors for noncontact graft rupture are similar to those previously identified for first-time noncontact ACL injury, and sex-specific differences exist.Study designCase-control study; Level of evidence, 3.MethodsEleven subjects who suffered a noncontact ACL graft rupture and 44 subjects who underwent ACL reconstruction but did not experience graft rupture were included in the study. Using magnetic resonance imaging, the geometries of the tibial plateau subchondral bone, articular cartilage, meniscus, tibial spines, and femoral notch were measured. Risk factors associated with ACL graft rupture were identified using Cox regression.ResultsThe following were associated with increased risk of ACL graft injury in males: increased posterior-inferior-directed slope of the articular cartilage in the lateral tibial plateau measured at 2 locations (hazard ratio [HR] = 1.50, P = .029; HR = 1.39, P = .006), increased volume (HR = 1.45, P = .01) and anteroposterior length (HR = 1.34, P = .0023) of the medial tibial spine, and increased length (HR = 1.18, P = .0005) and mediolateral width (HR = 2.19, P = .0004) of the lateral tibial spine. In females, the following were associated with increased risk of injury: decreased volume (HR = 0.45, P = .02) and height (HR = 0.46, P = .02) of the medial tibial spine, decreased slope of the lateral tibial subchondral bone (HR = 0.72, P = .01), decreased height of the posterior horn of the medial meniscus (HR = 0.09, P = .001), and decreased intercondylar notch width at the anterior attachment of the ACL (HR = 0.72, P = .02).ConclusionThe geometric risk factors for ACL graft rupture are different for males and females. For females, a decreased femoral intercondylar notch width and a decreased height of the posterior medial meniscus were risk factors for ACL graft rupture that have also been found to be risk factors for first-time injury. There were no risk factors in common between ACL graft injury and first-time ACL injury for males.

Dataset Information

Genetic Variants and Anterior Cruciate Ligament Rupture: A Systematic Review.

Publications

Genetic Variants and Anterior Cruciate Ligament Rupture: A Systematic Review.

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