A Phase II randomized controlled trial evaluated antithrombotic treatment with fesomersen in patients with kidney failure on hemodialysis.

Patients with kidney failure on hemodialysis (KF-HD) are at high risk for both atherothrombotic events and bleeding. This Phase IIb study evaluated the dose-response of fesomersen, an inhibitor of hepatic Factor XI expression, versus placebo, for bleeding and atherothrombosis in patients with KF-HD. Patients were randomized to receive fesomersen 40, 80, or 120 mg once-monthly, or matching placebo, for up to 12 months. The primary safety endpoint was a composite of major bleeding and clinically relevant non-major bleeding (MB/CRNMB). Exploratory endpoints included post-dialysis arterio-venous (AV)-access bleeding, major atherothrombotic events (composite of fatal or non-fatal myocardial infarction, ischemic stroke, acute limb ischemia/major amputation, systemic embolism, symptomatic venous thromboembolism), AV-access thrombosis, and clotting of the hemodialysis circuit. Of 308 participants randomized, 307 received study treatment and were analyzed. Fesomersen led to a dose-dependent and sustained reduction of steady-state median FXI levels by 53.6% (40 mg group), 71.3% (80 mg group), 86.0% (120 mg group), versus 1.9% in the placebo group. MB/CRNMB events occurred in 6.5% (40 mg group), 5.1% (80 mg group), 3.9% (120 mg group), and in 4.0% of those receiving placebo (pooled fesomersen versus placebo P = 0.78). Major atherothrombotic events occurred in 1 patient (1.3%) in each treatment arm. MB/CRNMB bleeding and post-dialysis AV-access bleeding were not related to predicted FXI levels. Lower predicted FXI levels were associated with reductions in hemodialysis circuit clotting (P = 0.002) and AV-access thrombosis (P = 0.014). In patients with KF-HD, fesomersen produced a dose-dependent reduction in FXI levels associated with similar rates of major bleeding compared with placebo. REGISTRATION: URL: https://www.clinicaltrials.gov; unique identifier: NCT04534114.

Befovacimab, an anti-tissue factor pathway inhibitor antibody: Early termination of the multiple-dose, dose-escalating Phase 2 study due to thrombosis.

INTRODUCTION: Befovacimab (formerly BAY 1093884) is a fully human monoclonal antibody able to bind to tissue factor pathway inhibitor (TFPI) and developed as a non-replacement therapy for individuals with haemophilia A/B, with or without inhibitors. AIM: To assess the safety of multiple escalating doses of befovacimab in individuals with severe haemophilia A/B with or without inhibitors. METHODS: In this non-randomised, open-label Phase 2 study (NCT03597022), adult males with <1% factor VIII or <2% factor IX and ≥4 bleeds in the previous six months were enrolled in three dose cohorts (100/225/400 mg). Participants received befovacimab subcutaneously once weekly. The primary endpoint was safety; secondary endpoints included annualised bleeding rate (ABR) and pharmacokinetics/pharmacodynamics (PK/PD) of befovacimab. RESULTS: A total of 24 participants (n = 8 in each dose cohort) were treated for 2-47 weeks. Patients treated with 100 mg and 225 mg doses of befovacimab demonstrated improved bleeding control compared with pre-study bleeding rates, with a dose-dependent effect. Dosing was suspended and the study prematurely terminated following three drug-related thrombotic serious adverse events (SAEs): two at the 225 mg dose and one at the 400 mg dose. These occurred in the absence of bleeding episodes or concomitant use of replacement/bypass therapies. No laboratory abnormalities were observed, and PK/PD data did not show correlation between SAE occurrence and levels of circulating befovacimab or free TFPI. CONCLUSION: Despite favourable initial results from preclinical and clinical studies, a positive safety profile of befovacimab was not confirmed. The lack of SAE-related laboratory abnormalities or differentiating PK/PD characteristics in participants experiencing SAEs raises concerns about the predictability of thrombosis following befovacimab treatment and emphasises the need for further investigation into the therapeutic window of anti-TFPI treatment.

Is the Use of Spreaders an Accurate Method for Ligament Balancing?

BACKGROUND: To analyze 2 methods of manual spreader gap assessment accuracy, visual vs blinded, compared with a controlled tensioner in total knee arthroplasty. METHODS: Twenty-two fresh frozen cadaver knees were used to perform total knee arthroplasty by 22 surgeons. Extension and flexion gaps were measured with empirical manual force application with spreaders in 2 different manners: (1) surgeons were blinded to gap geometry formation-blind method group (BM) and (2) surgeons viewed them-viewing method group (VM). A tensioner was used to measure the corresponding ligament tension applied during spreader measurements and to measure the extension and flexion gaps with standard force of 100 and 80 N (tensioner method [TM]) in each femorotibial compartment. RESULTS: All measurements with spreaders (VM and BM) presented extension and flexion gaps oversized and asymmetric (P < .0001), when compared with the same gaps measured with the tensioner. Approximately 63% (P = <0.001) and 77.3% (P = .161) of the VM group and 68.2% (P = .018) and 77.3% (P = .161) of the BM group demonstrated asymmetry for extension and flexion gaps up to 3 mm to the TM. Gaps measured in the VM group presented results with slightly less oversizing and asymmetries than the measurements in the BM group compared with TM, although significantly different (P < .0001). CONCLUSION: The assessment of extension and flexion gaps with empirical manual applied force spreaders produced oversized and asymmetric gaps compared with the use of tensioner. No visual influence was observed during the spreader applied empirical manual force compared with the blinded assessment.

Biomechanical comparison of different graft positions for single-bundle anterior cruciate ligament reconstruction.

PURPOSE: Recent reports have highlighted the importance of an anatomic tunnel placement for anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to compare the effect of different tunnel positions for single-bundle ACL reconstruction on knee biomechanics. METHODS: Sixteen fresh-frozen cadaver knees were used. In one group (n = 8), the following techniques were used for knee surgery: (1) anteromedial (AM) bundle reconstruction (AM-AM), (2) posterolateral (PL) bundle reconstruction (PL-PL) and (3) conventional vertical single-bundle reconstruction (PL-high AM). In the other group (n = 8), anatomic mid-position single-bundle reconstruction (MID-MID) was performed. A robotic/universal force-moment sensor system was used to test the knees. An anterior load of 89 N was applied for anterior tibial translation (ATT) at 0°, 15°, 30° and 60° of knee flexion. Subsequently, a combined rotatory load (5 Nm internal rotation and 7 Nm valgus moment) was applied at 0°, 15°, 30° and 45° of knee flexion. The ATT and in situ forces during the application of the external loads were measured. RESULTS: Compared with the intact ACL, all reconstructed knees had a higher ATT under anterior load at all flexion angles and a lower in situ force during the anterior load at 60° of knee flexion. In the case of combined rotatory loading, the highest ATT was achieved with PL-high AM; the in situ force was most closely restored with MIDMID, and the in situ force was the highest AM-AM at each knee flexion angle. CONCLUSION: Among the techniques, AM-AM afforded the highest in situ force and the least ATT.

Biomechanics of the human triple-bundle anterior cruciate ligament.

PURPOSE: To investigate the biomechanics of the intermediate (IM), anteromedial (AM), and posterolateral (PL) bundles in the human anterior cruciate ligament (ACL). METHODS: Eighteen human cadaveric knees were tested with a robotic/universal force-moment sensor testing system. Anterior tibial translation (ATT) was determined under an 89-N anterior tibial load. Coupled ATT was determined under a combined rotatory load of 7-Nm valgus and 5-Nm internal rotation torque (pivot moment). Each bundle's in situ forces were measured under identical external loading conditions. RESULTS: Under anterior load, the PL bundle's in situ force was highest at 0° and decreased during flexion. Under the anterior load, the AM bundle's in situ force was significantly higher than the IM and PL bundles' force at 15°, 30°, and 60°. Under the pivot moment, the AM bundle's in situ force was significantly higher than the PL and IM bundles' force at 0° and 15°, and the IM bundle had the lowest in situ force at 0° but higher in situ force than the AM and PL bundles at 30° and 45°. IM and AM bundle removal increased ATT under the anterior load at all angles. Cutting the PL bundle after IM and AM bundle removal (whole ACL removal) significantly increased ATT under the anterior load at 0°, 15°, and 30° of knee flexion and increased coupled ATT under the pivot moment at 0° and 15°. CONCLUSIONS: The biomechanical role of each of the 3 ACL bundles (AM, IM, and PL) was measured with a robotic/universal force-moment sensor testing system. The AM bundle stabilized the knee against both the anterior and rotatory loads. The PL bundle stabilized the knee especially near full extension. The IM bundle supported the AM and PL bundles through all flexion angles, especially from 30° to 45°, against the rotatory load. CLINICAL RELEVANCE: Knowledge of functions of the different ACL bundles will help improve ACL reconstruction techniques to enable restoration of normal knee function.

Measurement of the end-to-end distances between the femoral and tibial insertion sites of the anterior cruciate ligament during knee flexion and with rotational torque.

PURPOSE: The aim of this study was to determine the end-to-end distance changes in anterior cruciate ligament (ACL) fibers during flexion/extension and internal/external rotation of the knee. METHODS: The positional relation between the femur and tibia of 10 knees was digitized on a robotic system during flexion/extension and with an internal/external rotational torque (5 Nm). The ACL insertion site data, acquired by 3-dimensional scanning, were superimposed on the positional data. The end-to-end distances of 5 representative points on the femoral and tibial insertion sites of the ACL were calculated. RESULTS: The end-to-end distances of all representative points except the most anterior points were longest at full extension and shortest at 90°. The distances of the anteromedial (AM) and posterolateral (PL) bundles were 37.2 ± 2.1 mm and 27.5 ± 2.8 mm, respectively, at full extension and 34.7 ± 2.4 mm and 20.7 ± 2.3 mm, respectively, at 90°. Only 4 knees had an isometric point, which was 1 of the 3 anterior points. Under an internal torque, both bundles became longer with statistical meaning at all flexion angles (P = .005). The end-to-end distances of all points became longest with internal torque at full extension and shortest with an external torque at 90°. CONCLUSIONS: Only 4 of 10 specimens had an isometric point at a variable anterior point. The end-to-end distances of the AM and PL bundles were longer in extension and shorter in flexion. CLINICAL RELEVANCE: The nonisometric tendency of the ACL and the end-to-end distance change during knee flexion/extension and internal/external rotation should be considered during ACL reconstruction to avoid overconstraint of the graft.

PCL to graft impingement pressure after anatomical or non-anatomical single-bundle ACL reconstruction.

BACKGROUND: Anterior cruciate ligament (ACL) graft impingement against the posterior cruciate ligament (PCL) has been postulated, but not thoroughly investigated. PURPOSE: To evaluate PCL impingement pressure and biomechanical stability with different tibial and femoral tunnel positions in ACL reconstruction. METHODS: In 15 porcine knees, the impingement pressure between ACL and PCL was measured using pressure sensitive film before and after ACL single-bundle reconstruction. ACL reconstructions were performed in each knee with three different tibial and femoral tunnel position combinations: (1) tibial antero-medial (AM) tunnel to femoral AM tunnel (AM-AM), (2) tibial postero-lateral (PL) tunnel to femoral High-AM tunnel (PL-High-AM) and (3) tibial AM tunnel to femoral High-AM tunnel (AM-High-AM). Anterior tibial translation (ATT) was evaluated after each ACL reconstruction using robotic/universal force-moment sensor testing system. RESULTS: There was no significant difference of the impingement pressure between AM and AM, PL-High-AM reconstructed groups and intact ACL. Only AM-High-AM ACL reconstruction group showed significantly higher impingement pressure compared with intact ACL. With regard to ATT, AM-AM group had significantly higher stiffness than PL-High-AM group. CONCLUSION: Anatomical ACL reconstruction does not cause PCL impingement and it has biomechanical advantage in ATT when compared with non-anatomical ACL reconstructions in porcine knee. For the clinical relevance, in the anatomical ACL reconstruction, no ACL-PCL impingement is found.

Anterior cruciate ligament tunnel position measurement reliability on 3-dimensional reconstructed computed tomography.

PURPOSE: The purpose of this study was to evaluate intraobserver and interobserver reliability of anterior cruciate ligament tunnel location measurement by use of 3-dimensional reconstructed computed tomography (CT). METHODS: Three-dimensional reconstructed CT images of 31 cadaveric knees were used in this study. Twenty-one knees were operated on with a double-bundle technique, and ten knees were operated on with a single-bundle technique. Femoral tunnel location was measured with 3 methods on the medial-lateral view of the lateral femoral condyle in the strictly lateral position. Tibial tunnel location was measured in the top view of the proximal tibia. The images were evaluated independently by 2 orthopaedic surgeons. A second measurement was performed, by both testers, after a 4-week interval. RESULTS: The 3 methods of femoral tunnel location measurement had intraobserver intraclass correlation coefficients (ICCs) that ranged from 0.963 to 0.998 and interobserver ICCs that ranged from 0.993 to 0.999. Tibial tunnel measurement had intraobserver ICCs that varied between 0.957 and 0.998 and interobserver ICCs that varied between 0.993 and 0.996. CONCLUSIONS: The measurement of the anterior cruciate ligament tunnel location on 3-dimensional reconstructed CT provided excellent intraobserver and interobserver reliability. CLINICAL RELEVANCE: Three-dimensional reconstructed CT can be used for further studies to assess the effect of tunnel position on knee stability and patient outcomes.

A biomechanical comparison of 2 femoral fixation techniques for anterior cruciate ligament reconstruction in skeletally immature patients: over-the-top fixation versus transphyseal technique.

PURPOSE: The purpose of this study was to compare knee kinematics and in situ forces of the graft between 2 femoral fixation techniques of anterior cruciate ligament (ACL) reconstruction: the over-the-top (OTT) fixation and transphyseal (TP) techniques. METHODS: ACL reconstruction in skeletally immature patients is a challenging procedure. Regarding the femoral fixation techniques, 2 methods are commonly used: the OTT fixation and TP techniques. Ten cadaveric knees (mean age, 57 years; range, 48 to 65 years) were tested with the robotic/universal force-moment sensor system by use of (1) an 89-N anterior tibial load at full extension and 15°, 30°, 60°, and 90° of knee flexion and (2) a combined 7-Nm valgus torque and 5-Nm internal tibial rotation torque at 15° and 30° of knee flexion. RESULTS: Both OTT and TP ACL reconstruction techniques closely restored the intact knee kinematics and had a significant reduction in anterior tibial translation under an anterior tibial load and in coupled anterior tibial translation under a combined rotatory load when compared with an ACL-deficient knee. When both ACL reconstruction techniques were compared, the only difference found was that the in situ force of the ACL graft reconstructed with the OTT technique in response to a combined rotatory load at 30° of flexion was significantly lower than the ACL graft reconstructed with the TP technique (5.3 ± 3.3 N and 10.7 ± 6.0 N, respectively; P = .013). CONCLUSIONS: This time 0 testing showed that both ACL reconstruction techniques, OTT and TP, can reproduce the kinematics of the intact knee in response to an anterior tibial load and a combined rotatory load. CLINICAL RELEVANCE: Both femoral fixation techniques exhibited comparable time 0 kinematics when subjected to simulated clinical examination loading conditions.

Anatomic double-bundle anterior cruciate ligament reconstruction restores patellofemoral contact areas and pressures more closely than nonanatomic single-bundle reconstruction.

PURPOSE: To investigate the effects of anterior cruciate ligament (ACL) deficiency and nonanatomic single-bundle (SB) and anatomic double-bundle (DB) ACL reconstruction on the contact characteristics of the patellofemoral (PF) joint. METHODS: By use of a materials testing system, 7 fresh-frozen human cadaveric knees were tested. The following states were tested: ACL-intact knee, nonanatomic SB ACL reconstruction, anatomic DB ACL reconstruction, and ACL-deficient knee. Hamstring autografts were used. PF contact pressures and areas were measured with pressure-sensitive film at 30°, 60°, and 90° of knee flexion with a constant 100-N load on the quadriceps tendon. RESULTS: The total contact area of ACL-deficient and nonanatomic SB ACL-reconstructed knees (123.8 ± 63.9 and 149.6 ± 79.3 mm(2), respectively) significantly decreased when compared with those of the intact knee (206.1 ± 83.6 mm(2)) at 30° of knee flexion. The lateral-facet peak pressure of ACL-deficient and nonanatomic SB ACL-reconstructed knees (1.12 ± 0.52 and 1.22 ± 0.54 MPa, respectively) significantly decreased when compared with those of the intact knee (0.68 ± 0.38 MPa) at 90° of knee flexion. Anatomic DB ACL reconstruction restored the contact pressures and areas to values similar to those of the intact knee (no significant difference). CONCLUSIONS: ACL deficiency resulted in a significant decrease in the total and medial PF contact areas and in an increase in the lateral PF contact pressure. Anatomic DB ACL reconstruction more closely restored normal PF contact area and pressure than did nonanatomic SB ACL reconstruction. CLINICAL RELEVANCE: Our findings suggest that the changes in the PF contact area and pressures in ACL deficiency and after nonanatomic SB ACL reconstruction may be one of the causes of PF osteoarthritis or other related PF problems found at long-term follow-up. Anatomic DB ACL reconstruction may reduce the incidence of PF problems by closely restoring the contact area and pressure.

Changes in ACL length at different knee flexion angles: an in vivo biomechanical study.

Recently, there has been a tremendous impetus on anatomical reconstruction of the anterior cruciate ligament (ACL), and the double-bundle reconstruction concept has been advocated by many authors. It is, therefore, important to understand how the lengths of the two bundles of the ACL vary during different knee flexion angles as this could influence the angle of graft fixation during surgery. The aim of this study is to determine the change in length of the ACL bundles during different knee flexion angles. Ten subjects with normal knees were evaluated. A high-resolution computer tomography scan was performed, and 3D knee images were obtained. These images were then imported to customized software, and digital length measurement of four virtual bundles (anatomical single bundle, AM, PL and over the top) was evaluated from fixed points on the femur and tibia. Length-versus-flexion curves were drawn, and statistical analysis was performed to evaluate changes in length for each bundle at varying angles of knee flexion (0 degrees, 45 degrees, 90 degrees and 135 degrees). All virtual bundles achieved greatest lengths at full extension. There was a significant difference between the posterolateral bundle length when compared to the other bundles at full extension. There were no significant differences between the lengths of the anteromedial and the over the top single bundles at all angles of knee flexion. Three-dimensional computer tomography can be used to assess the length changes of the virtual anterior cruciate ligament bundles, thereby allowing a better understanding of bundle function in clinical situations.

Biomechanics of the porcine triple bundle anterior cruciate ligament.

Several species of animals are used as a model to study human anterior cruciate ligament (ACL) reconstruction. In many animals, three bundles were clearly discernible during dissection in the ACL. However, there are few reports about the biomechanical role of each bundle in the porcine knee. The purpose of this study is to investigate the role of each of the three bundles in the porcine knee, especially the intermediate bundle. Ten porcine knees were tested using a robotic/universal forcemoment sensor system. This system applied anterior loading of 89 N at 30 degrees, 60 degrees and 90 degrees of flexion, and a combined 7 Nm valgus and 4 Nm internal tibial torque at 30 degrees and 60 degrees of flexion before and after each bundle was selectively cut. The in situ force (N) for each bundle of the ACL was measured. Both intermediate (IM) bundle and postero-lateral (PL) bundle had significantly lower in situ force than the antero-medial (AM) bundle in anterior loading. The IM and PL bundles carried a larger proportion of the force under the torsional loads than the anterior loads. But IM bundle had a significant lower in situ force during the combined torque at 60 degrees of knee flexion, when compared intact ACL. In summary, IM bundle has a subordinate role to the AM and PL bundles. AM bundle is more dominant than IM and PL bundles. The porcine knee is a suitable model for ACL studies, especially for AP stability.

Effect of tunnel position for anatomic single-bundle ACL reconstruction on knee biomechanics in a porcine model.

Attention has been focused on the importance of anatomical tunnel placement in anterior cruciate ligament (ACL) reconstruction. The purpose of this study was to compare the effect of different tunnel positions for single-bundle (SB) ACL reconstruction on knee kinematics. Ten porcine knees were used for the following reconstruction techniques: three different anatomic SB [AM-AM (antero-medial), PL-PL (postero-lateral), and MID-MID] (n = 5 for each group), conventional SB (PL-high AM) (n = 5), and anatomic double-bundle (DB) (n = 5). Using a robotic/universal force-moment sensor testing system, an 89 N anterior load (simulated KT1000 test) at 30, 60, and 90 degrees of knee flexion and a combined internal rotation (4 N m) and valgus (7 N m) moment (simulated pivot-shift test) at 30 and 60 degrees were applied. Anterior tibial translation (ATT) (mm) and in situ forces (N) of reconstructed grafts were calculated. During simulated KT1000 test at 60 degrees of knee flexion, the PL-PL had significantly lower in situ force than the intact ACL (P < 0.01). In situ force of the MID-MID was higher than other SB reconstructions (at 30 degrees : 94.8 +/- 2.5 N; at 60 degrees : 85.2 +/- 5.3 N; and 90 degrees: 66.0 +/- 8.7 N). At 30 degrees of knee flexion, the PL-high AM had the lowest in situ values (67.1 +/- 19.3 N). At 60 and 90 degrees of knee flexion the PL-PL had the lowest in situ values (at 60 degrees : 60.8 +/- 19.9 N; 90 degrees : 38.4 +/- 19.2 N). The MID-MID and DB had no significant in situ force differences at 30 and 60 degrees of knee flexion. During simulated pivot-shift test at 60 degrees of knee flexion, the PL-PL and PL-high AM reconstructions had a significant lower in situ force than the intact ACL (P < 0.01). During simulated KT1000 test at 30, 60, and 90 degrees of knee flexion, the PL-PL and PL-high AM had significantly lower ATT than the intact ACL (P < 0.01). During simulated KT1000 test at 60 and 90 degrees, the MID-MID, AM-AM, and DB had significantly lower ATT than the ACL deficient knee (P < 0.01). During simulated KT1000 test at 90 degrees, every reconstructed knee had significantly higher ATT than the intact knee (P < 0.01). In conclusion, the MID-MID position provided the best stability among all anatomic SB reconstructions and more closely restored normal knee kinematics.

Evaluation of the tunnel placement in the anatomical double-bundle ACL reconstruction: a cadaver study.

The objective of this study was to investigate the accurate AM and PL tunnel positions in an anatomical double-bundle ACL reconstruction using human cadaver knees with an intact ACL. Fifteen fresh-frozen non-paired adult human knees with a median age of 60 were used. AM and PL bundles were identified by the difference in tension patterns. First, the center of femoral PL and AM bundles were marked with a K-wire and cut from the femoral insertion site. Next, each bundle was divided at the tibial side, and the center of each AM and PL tibial insertion was again marked with a K-wire. Tunnel placement was evaluated using a C-arm radiographic device. For the femoral side assessment, Bernard and Hertel's technique was used. For the tibial side assessment, Staubli's technique was used. After radiographic evaluations, all tibias' soft tissues were removed with a 10% NaOH solution, and tunnel placements were evaluated. In the radiographic evaluation, the center of the femoral AM tunnel was placed at 15% in a shallow-deep direction and at 26% in a high-low direction. The center of the PL bundle was found at 32% in a shallow-deep direction and 52% in a high-low direction. On the tibial side, the center of the AM tunnel was placed at 31% from the anterior edge of the tibia, and the PL tunnel at 50%. The ACL tibial footprint was placed close to the center of the tibia and was oriented sagittally. AM and PL tunnels can be placed in the ACL insertions without any coalition. The native ACL insertion site has morphological variety in both the femoral and tibial sides. This study showed, anatomically and radiologically, the AM and PL tunnel positions in an anatomical ACL reconstruction. We believe that this study will contribute to an accurate tunnel placement during ACL reconstruction surgery and provide reference data for postoperative radiographic evaluation.

Contribution of the meniscofemoral ligament as a restraint to the posterior tibial translation in a porcine knee.

The meniscofemoral ligament (MFL) is a major structure in the posterior aspect of the porcine knee together with the posterior cruciate ligament (PCL). While the porcine knee is a frequently used animal model for biomechanical evaluation of PCL reconstruction techniques, the contribution of the MFL to stability of the porcine knee is not well understood. The purpose of this study is (1) to evaluate the kinematics of the knee after sequential cutting of the PCL and MFL and (2) to determine the in situ forces of the PCL and MFL in response to a posterior tibial load of 89 N using the robotic/universal force-moment sensor system from 15 degrees to 90 degrees of knee flexion. Ten porcine knees were used in this study. The magnitude of posterior tibial translation under a posterior tibial load was significantly increased (P < 0.01) after sequential transection of the PCL and the MFL at each testing angle compared to the intact condition. The in situ force of the PCL was highest at 60 degrees of flexion (82.3 +/- 8.6 N) and lowest at 15 degrees of flexion (45.1 +/- 15.9 N). The in situ force of the MFL was highest at 15 degrees of flexion (24.3 +/- 6.5 N) and lowest at 90 degrees of flexion (12.9 +/- 10.5 N). The findings in this study revealed a biomechanical contribution of the MFL as the secondary restraint to the posterior tibial translation in conjunction with the PCL especially near full extension.

The effect of high doses of ω-3 fatty acid on the structure of the gastrocnemius muscle and on the lipidic profile of Wistar rats submitted to swimming.

OBJECTIVES: Evidence suggests that ω-3 fatty acids (FA) may have an anabolic effect on skeletal muscle. However, questions about dosage, frequency, combined protein supplementation, or different physical exercises remain unanswered. The aim of this study was to quantify by stereology whether supplementation with high dosages of ω-3 FA combined with swimming has an anabolic effect on the skeletal musculature and on the lipid profile of rats. METHODS: Sixty male Wistar rats were divided into four groups: placebo sedentary (PS), ω-3 FA sedentary (ω-3 S), placebo exercise (PE), and ω-3 FA exercise (ω-3 E). The animals in the PE and ω-3 E groups were submitted to swimming 5 d/wk, with an overload of 15% of body weight. The animals received ω-3 FA or olive oil (placebo) by gavage. After sacrifice, blood samples and the gastrocnemius muscle were collected for analysis. RESULTS: Results from this study did not show a difference in the cross-sectional areas of the gastrocnemius muscle between groups. The administration of high doses of ω-3 FA reduced plasmatic concentrations of low-density lipoprotein. Additionally, an interaction effect was observed between physical exercise and supplementation with ω-3 on levels of high-density lipoprotein. Therefore, the association between these two treatments increased high-density lipoprotein levels. CONCLUSIONS: The administration of high doses of ω-3 associated with physical activity may be beneficial in the treatment of dyslipidemia. High doses of ω-3 FA do not cause muscle mass alteration.

Intercondylar roof impingement pressure after anterior cruciate ligament reconstruction in a porcine model.

Anterior cruciate ligament (ACL) graft impingement against the intercondylar roof has been postulated, but not thoroughly investigated. The roof impingement pressure changes with different tibial and femoral tunnel positions in ACL reconstruction. Anterior tibial translation is also affected by the tunnel positions of ACL reconstruction. The study design included a controlled laboratory study. In 15 pig knees, the impingement pressure between ACL and intercondylar roof was measured using pressure sensitive film before and after ACL single bundle reconstruction. ACL reconstructions were performed in each knee with two different tibial and femoral tunnel position combinations: (1) tibial antero-medial (AM) tunnel to femoral AM tunnel (AM to AM) and (2) tibial postero-lateral (PL) tunnel to femoral High-AM tunnel (PL to High-AM). Anterior tibial translation (ATT) was evaluated after each ACL reconstruction using robotic/universal force-moment sensor testing system. Neither the AM to AM nor the PL to High-AM ACL reconstruction groups showed significant difference when compared with intact ACL in roof impingement pressure. The AM to AM group had a significantly higher failure load than PL to High-AM group. This study showed how different tunnel placements affect the ACL-roof impingement pressure and anterior-posterior laxity in ACL reconstruction. Anatomical ACL reconstruction does not cause roof impingement and it has a biomechanical advantage in ATT when compared with non-anatomical ACL reconstructions in the pig knee. There is no intercondylar roof impingement after anatomical single bundle ACL reconstruction.

Effects of knee flexion angle and loading conditions on the end-to-end distance of the posterior cruciate ligament: a comparison of the roles of the anterolateral and posteromedial bundles.

BACKGROUND: It is commonly accepted that the anterolateral (AL) bundle of the posterior cruciate ligament (PCL) is tight in flexion and that the posteromedial (PM) bundle is tight in extension. However, a recent in vivo study showed that both bundles were tight in extension. PURPOSE: To investigate the effects of knee flexion angle, rotational torque, and anterior/posterior translational force on the end-to-end distance between the femoral and tibial insertion sites of each bundle of the PCL. STUDY DESIGN: Descriptive laboratory study. METHODS: Cadaveric knees (10 specimens) were mounted on a robotic system, and the relative positional data between the femur and tibia were acquired during passive flexion/extension, with an applied 5-N·m rotational torque and an applied 89-N translational force. The bony surface and PCL insertion data were acquired with a 3-dimensional scanner after gross dissection and were superimposed onto the positional data. The end-to-end distance between the 2 PCL insertion sites of the femur and tibia was measured. RESULTS: The end-to-end distance increased from full extension to 90° for both the AL (9.2 ± 1.8 mm; from 30.0 to 39.2 mm) and PM bundles (5.8 ± 2.2 mm; from 32.0 to 37.7 mm). With an internal rotational torque, the end-to-end distance of the PM bundle increased significantly (P < .05) at 0°, 30°, and 60° of knee flexion. Under a posterior translational force at 90° of knee flexion, the length of both bundles increased to their longest measurements (AM bundle: 40.6 ± 4.2 mm; PM bundle: 38.4 ± 3.8 mm). CONCLUSION: The end-to-end distance of the AL and PM bundles of the PCL increased in flexion, and this pattern was maintained during tests with posterior translational force. The PM bundle was more affected by the rotational torque than was the AL bundle. CLINICAL RELEVANCE: Both bundles of the PCL may serve a greater functional role in flexion than in extension. The PM bundle might be more important for the control of rotation than the AL bundle. Posterior translation at 90° of knee flexion could be the most stressful condition for both bundles of the PCL, which may have implications for an injury mechanism.

The use of blood vessel-derived stem cells for meniscal regeneration and repair.

PURPOSE: Surgical repairs of tears in the vascular region of the meniscus usually heal better than repairs performed in the avascular region; thus, we hypothesized that this region might possess a richer supply of vascular-derived stem cells than the avascular region. METHODS: In this study, we analyzed 6 menisci extracted from aborted human fetuses and 12 human lateral menisci extracted from adult human subjects undergoing total knee arthroplasty. Menisci were immunostained for CD34 (a stem cell marker) and CD146 (a pericyte marker) in situ, whereas other menisci were dissected into two regions (peripheral and inner) and used to isolate meniscus-derived cells by flow cytometry. Cell populations expressing CD34 and CD146 were tested for their multilineage differentiation potentials, including chondrogenic, osteogenic, and adipogenic lineages. Fetal peripheral meniscus cells were transplanted by intracapsular injection into the knee joints of an athymic rat meniscal tear model. Rat menisci were extracted and histologically evaluated after 4 wk posttransplantation. RESULTS: Immunohistochemistry and flow cytometric analyses demonstrated that a higher number of CD34- and CD146-positive cells were found in the peripheral region compared with the inner region. The CD34- and CD146-positive cells isolated from the vascular region of both fetal and adult menisci demonstrated multilineage differentiation capacities and were more potent than cells isolated from the inner (avascular) region. Fetal CD34- and CD146-positive cells transplanted into the athymic rat knee joint were recruited into the meniscal tear sites and contributed to meniscus repair. CONCLUSIONS: The vascularized region of the meniscus contains more stem cells than the avascular region. These meniscal-derived stem cells were multipotent and contributed to meniscal regeneration.