Assessing knee joint biomechanics and trunk posture according to medial osteoarthritis severity.

During progression of knee osteoarthritis (OA), gait biomechanics changes three-dimensionally; however, its characteristics and trunk posture according to OA severity remain unknown. The present study investigated three-dimensional knee joint biomechanics and trunk posture according to knee OA severity. Overall, 75 patients (93 knees) with medial knee OA [Kellgren-Lawrence grade ≥ 2, grade 2: 20 patients with 24 knees (mean 60.0 years old); grade 3: 25 with 28 knees (mean 62.0 years old); grade 4: 30 with 41 knees (mean 67.9 years old)] and 14 healthy controls (23 knees, mean 63.6 years old) underwent gait analysis using an optical motion capture system and point cluster technique. In grade 2 knee OA, the relative contribution of the knee adduction moment (KAM) increased significantly (P < 0.05), and that of the knee flexion moment decreased (P < 0.05) prior to significant progression of varus knee deformity. Grade 3 knee OA showed significant exacerbation of varus knee deformity (P < 0.01) and KAM increase (P < 0.001). The maximum knee extension angle decreased (P < 0.05) and trunk flexion increased during gait in grade 4 knee OA (P < 0.001). Our study clarified the kinematics and kinetics of medial knee OA with trunk flexion according to severity. Kinetic conversion occurred in grade 2 knees prior to progression of varus deformities, knee flexion contractures, and sagittal imbalance during gait in patients with severe knee OA.

Higher Association of Pelvis-Knee-Ankle Angle Compared With Hip-Knee-Ankle Angle With Knee Adduction Moment and Patient-Reported Outcomes After High Tibial Osteotomy.

BACKGROUND: High tibial osteotomy (HTO) reduces the load distribution of the medial compartment by modifying leg alignment. Knee adduction moment (KAM), a surrogate measure of dynamic loading in the knee joint, decreases after HTO. However, leg alignment does not fully account for KAM. PURPOSE: To assess the association between the pelvis-knee-ankle angle (PKA), a novel radiographic parameter reflecting leg alignment and pelvic width, and KAM and patient-reported outcomes after HTO. STUDY DESIGN: Cross sectional study; Level of evidence, 3. METHODS: PKA is the angle between the line from the midpoint of the anterior superior iliac spine to the center of the knee joint and the mechanical axis of the tibia. In this study, 54 patients with medial compartment knee osteoarthritis and varus alignment who underwent 3-dimensional gait analysis preoperatively and 2 years after medial open-wedge HTO were evaluated. The primary outcomes were hip-knee-ankle angle (HKA), PKA, KAM peaks, and Knee Society Score (KSS). Single and multivariate regression analysis including PKA and KAM peaks as well as other demographic and radiologic factors was performed. RESULTS: HKA was weakly correlated with the first peak KAM (r = -0.33; P < .01) and second peak KAM (r = -0.27; P = .01) before HTO, but not significantly correlated after HTO. PKA was moderately correlated with the first peak KAM (r = 0.45; P < .01) and second peak KAM (r = 0.45; P < .01) before HTO and with the first peak KAM (r = 0.51; P < .01) and second peak KAM (r = 0.56; P < .01) after HTO. Multivariate linear regression revealed that postoperative PKA was still associated with the KAM peaks after HTO. Only postoperative PKA was correlated with the KSS satisfaction subscale (r = -0.30; P = .03). CONCLUSION: Although HKA was not correlated with KAM peaks after HTO, PKA was significantly correlated with KAM peaks in patients with varus knee osteoarthritis after HTO.

Novel Inhibitor for Downstream Targeting of Transforming Growth Factor-ß Signaling to Suppress Epithelial to Mesenchymal Transition and Cell Migration.

Cancer metastasis accounts for most of the mortality associated with solid tumors. However, antimetastatic drugs are not available on the market. One of the important biological events leading to metastasis is the epithelial to mesenchymal transition (EMT) induced by cytokines, namely transforming growth-factor-ß (TGF-ß). Although several classes of inhibitors targeting TGF-ß and its receptor have been developed, they have shown profound clinical side effects. We focused on our synthetic compound, HPH-15, which has shown anti-fibrotic activity via the blockade of the TGF-ß Smad-dependent signaling. In this study, 10 µM of HPH-15 was found to exhibit anti-cell migration and anti-EMT activities in non-small-cell lung cancer (NSCLC) cells. Although higher concentrations are required, the anti-EMT activity of HPH-15 has also been observed in 3D-cultured NSCLC cells. A mechanistic study showed that HPH-15 inhibits downstream TGF-ß signaling. This downstream inhibition blocks the expression of cytokines such as TGF-ß, leading to the next cycle of Smad-dependent and -independent signaling. HPH-15 has AMPK-activation activity, but a relationship between AMPK activation and anti-EMT/cell migration was not observed. Taken together, HPH-15 may lead to the development of antimetastatic drugs with a new mechanism of action.

Kinematics and center of axial rotation during walking after medial pivot type total knee arthroplasty.

PURPOSE: In recent years, the medial pivot (MP) type total knee arthroplasty (TKA) implant has been developed and marketed for achieving more natural kinematics with MP. However, little is known about the pivot pattern during walking after MP type TKA. This study aimed to determine the kinematics and center of axial rotation during walking after MP type TKA. METHODS: This randomized prospective study enrolled 40 patients with MP type TKA, 20 with cruciate-substituting TKA (MP-CS group), 20 with posterior-stabilized TKA (MP-PS group), and 10 healthy volunteers (control group). The kinematics and center of axial rotation during overground walking were measured by a three-dimensional motion analysis system. The six-degrees-of-freedom kinematics of the knee were calculated by the point cluster method. RESULTS: The amount of change in knee flexion in early stance phase was significantly lower in the MP-CS and MP-PS groups than in the control group. The femur showed anterior translation during early stance phase in all three groups. The median center of axial rotation in the transverse plane was predominantly on the lateral side of the knee during stance in all groups. CONCLUSIONS: Kinematics during gait are thought to be determined by physical posture, the kinetic chain during weight-bearing, and the kinematic features of adjacent structures, such as the behavior of the biarticular muscles. MP-CS and MP-PS did not necessarily induce rotational motion centered on the medial ball-in-socket component during walking; translational and lateral pivoting movements were also observed. Long-term follow-up is needed to monitor for polyethylene wear and implant loosening.

Side-to-side differences of three-dimensional knee kinematics during walking by normal subjects.

[Purpose] The purpose of this study was to determine the normal range of the side-to-side difference in three dimensional knee kinematics measured by the point cluster technique (PCT). [Subjects] The subjects were twenty-one healthy normal volunteers without knee pain or an episode of injury to the legs. [Methods] The subjects were tested bilaterally at a self-selected normal walking speed and six degrees of freedom knee kinematics were measured using the PCT, and the 95% confidence intervals of the average side-to-side differences in flexion-extension (FE), adduction-abduction (AA), internal-external (IE) rotation, and anterior-posterior (AP), medial-lateral (ML), superior-inferior (SI) translation in each stage of the gait cycle were determined. [Results] The average side-to-side differences and their 95% confidence intervals in rotation/translation in each stage of the gait cycle were determined. The side-to-side differences in AA rotation and AP translation of the tibia were significantly larger in the swing phase than in the stance phase. [Conclusion] The side-to-side differences in AA rotation and AP translation were highly dependent on the stage of the gait cycle. Therefore, the normal ranges of the side-to-side differences in knee kinematics in each stage of the gait cycle, in particular AA rotation and AP translation of the tibia, is useful information for evaluating knee kinematics during walking.

The effect of an ankle brace on the 3-dimensional kinematics and tibio-talar contact condition for lateral ankle sprains.

Ten fresh-frozen cadaveric ankles were studied to investigate the effect of an ankle brace (Air-Stirrup) on the three-dimensional (3-D) motion and contact-pressure distribution of the talo-tibial joint with lateral ligamentous injury. Three-dimensional motion and contact-pressure distribution were simultaneously measured under dynamic conditions employing a direct linear-transformation technique and a dynamic-pressure sensor, respectively. Inversion increased significantly upon severing of the anterior talo-fibular (ATF) ligament and calcaneo-fibular (CF) ligaments; however, restoration to the intact level was observed following application of the ankle brace. Internal rotation also increased upon severing of the lateral ligaments in the plantar flexion; however, this difference was not altered by using the ankle brace. The contact area on the articular surface of the talus shifted from posterior to anterior between plantar flexion and dorsal flexion; additionally, a high pressure area was evident in the medial aspect of the talus following severing of the lateral ligaments. Upon application of the ankle brace, however, no significant changes were apparent in the contact condition. The results of this study suggest that stabilization against inversion is the major function of braces in terms of protection of ankle sprains. Ankle sprains, however, often occur in combinations of inversion, plantar flexion and internal rotation; therefore, restriction of plantar flexion and internal rotation may also be an important function of the ankle brace.