Background: Three different techniques of anterior cruciate ligament (ACL) reconstruction—conventional (transtibial) single bundle (CSB), anatomic single bundle (ASB), and anatomic double bundle (ADB)—have been described. Purpose: To determine if double-bundle reconstruction is needed to restore rotational stability or if anatomic placement of a single bundle can yield similar results. Study Design: Randomized controlled trial; Level of evidence, 1. Methods: From December 2005 to December 2007, 320 patients were prospectively randomized into 3 groups: ADB, ASB, and CSB reconstruction. The average follow-up was 51.15 months (range, 39-63 months). At the final follow-up, 281 patients were available. In all groups, hamstring tendons were used with suspensory fixation on the femoral side and bioabsorbable interference screw fixation on the tibial side. The outcomes were evaluated by an independent blinded observer using the Lysholm score and subjective International Knee Documentation Committee (IKDC) form. The KT-1000 arthrometer was used to evaluate anteroposterior stability, and the pivot-shift test was used to determine rotational stability. Results: Anatomic single-bundle reconstruction resulted in better anteroposterior and rotational stability than CSB reconstruction (average side-to-side difference for anterior tibial translation was 1.6 mm in the ASB group vs 2.0 mm in the CSB group; P = .002). Negative pivot shift was 66.7% vs 41.7% (P = .003). In other parameters, the differences between groups were not statistically significant. The results of the ADB group were also superior to the ASB group for anteroposterior and rotational stability (average side-to-side difference for anterior tibial translation was 1.2 mm in the ADB group vs 1.6 mm in the ASB group; P = .002). Negative pivot shift was 93.1% vs 66.7%, respectively (P < .001), and range of motion was also significantly different (P = .005). The Lysholm score was 90.9, 91.8, and 93.0 in the CSB, ASB, and ADB groups, respectively. The difference was significant only when we compared ADB and CSB (P = .025). Subjective IKDC scores were 90.2, 90.6, and 92.1 in the CSB, ASB, and ADB groups, respectively. The difference was not significant. Conclusion: Anatomic double-bundle ACL reconstruction is significantly superior to conventional single-bundle ACL reconstruction and better than anatomic single-bundle reconstruction. Anatomic single-bundle reconstruction was superior to conventional single-bundle reconstruction. However, these differences are small and may not be clinically relevant.

Background: Reconstruction of the anterior cruciate ligament (ACL) has become a commonly performed procedure. However, biomechanical studies have demonstrated that conventional single-bundle ACL reconstruction techniques are only successful in limiting anterior tibial translation but less effective for restoring rotatory laxity. Purpose: This study aimed to compare the results of single- and double-bundle ACL reconstruction using an anatomic technique, individualized based on the patient’s native ACL size. The authors hypothesized that there would be no difference between the results of anatomic single-bundle (ASB) and anatomic double-bundle (ADB) reconstruction when the surgical technique is individualized. Study Design: Cohort study; Level of evidence, 2. Methods: Depending on intraoperative measurements of the ACL insertion site size, patients were selected for either ASB (n = 32) or ADB (n = 69) ACL reconstruction. In all groups, hamstring tendons autograft was used with suspensory fixation on the femoral side and bioabsorbable interference screw fixation on the tibial side. The outcomes were evaluated by an independent blinded observer using the Lysholm score, subjective International Knee Documentation Committee (IKDC) form, KT-1000 arthrometer for anteroposterior stability, and pivot-shift test for rotational stability. The average follow-up was 30 months (range, 26-34 months). There were no statistically significant differences in the baseline demographics of the 2 groups. Results: There was no significant difference between the ADB and ASB groups for Lysholm score (93.9 vs 93.5), subjective IKDC score (93.3 vs 93.1), anterior tibial translation (1.5- vs 1.6-mm side-to-side difference), and pivot shift (92% vs 90% with negative pivot-shift examination). Conclusion: Anatomic double-bundle reconstruction is not superior to anatomic single-bundle reconstruction when an individualized ACL reconstruction technique is used.

Cancers harbor many somatic mutations and germline variants, we hypothesized that the combined effect of germline variants that alter the structure, expression, or function of protein-coding regions of cancer-biology related genes (gHFI) determines which and how many somatic mutations (sM) must occur for malignant transformation. We show that gHFI and sM affect overlapping genes and the average number of gHFI in cancer hallmark genes is higher in patients who develop cancer at a younger age (r = −0.77, P = 0.0051), while the average number of sM increases in increasing age groups (r = 0.92, P = 0.000073). A strong negative correlation exists between average gHFI and average sM burden in increasing age groups (r = −0.70, P = 0.017). In early-onset cancers, the larger gHFI burden in cancer genes suggests a greater contribution of germline alterations to the transformation process while late-onset cancers are more driven by somatic mutations.

Long-term muscle weakness may increase the risk of knee reinjury after anterior cruciate ligament reconstruction (ACLR) and of osteoarthritis. The incidence of secondary injuries after ACLR and the predictive value of preoperative and postoperative limb symmetry index (LSI) and estimated preinjury capacity (EPIC) index were studied for predicting the risk of reinjury in a retrospective study. Sixty-three recreational and professional athletes after ACLR with hamstring autograft were followed for secondary injury in the period from 2012 to 2014, 5 years after ACLR. Peak torque values of knee extensor and flexor muscle strength of the involved and uninvolved limb were measured with an isokinetic dynamometer at 60 degrees per second before ACLR and 6 months after ACLR and were used to calculate LSI and EPIC index. The results suggest that the preoperative LSI and EPIC indexes predict a secondary ACL injury better than the postoperative LSI for extensor muscles which is often used as a criterion to determine the time for returning to normal sports activities. Individuals with secondary ACL injuries suffer greater loss of knee extensor muscle strength of the uninvolved limb between preoperative and postoperative ACLR testing compared to the individuals without secondary injury.

Background: The diversity of genomic alterations in cancer poses challenges to fully understanding the etiologies of the disease. Recent interest in infrequent mutations, in genes that reside in the “long tail” of the mutational distribution, uncovered new genes with significant implications in cancer development. The study of cancer-relevant genes often requires integrative approaches pooling together multiple types of biological data. Network propagation methods demonstrate high efficacy in achieving this integration. Yet, the majority of these methods focus their assessment on detecting known cancer genes or identifying altered subnetworks. In this paper, we introduce a network propagation approach that entirely focuses on prioritizing long tail genes with potential functional impact on cancer development. Results: We identify sets of often overlooked, rarely to moderately mutated genes whose biological interactions significantly propel their mutation-frequency-based rank upwards during propagation in 17 cancer types. We call these sets “upward mobility genes” and hypothesize that their significant rank improvement indicates functional importance. We report new cancer-pathway associations based on upward mobility genes that are not previously identified using driver genes alone, validate their role in cancer cell survival in vitro using extensive genome-wide RNAi and CRISPR data repositories, and further conduct in vitro functional screenings resulting in the validation of 18 previously unreported genes. Conclusion: Our analysis extends the spectrum of cancer-relevant genes and identifies novel potential therapeutic targets.