Although the lateral collateral ligament (LCL) passes in close proximity, the lateral meniscus has no attachment to this structure.The joint capsule attaches to the entire periphery of each meniscus but adheres more firmly to the medial meniscus. An interruption in the attachment of the joint capsule to the lateral meniscus, forming the popliteal hiatus, allows the popliteus tendon to pass through to its femoral attachment site. Contraction by the popliteus during knee flexion pulls the lateral meniscus posteriorly, avoiding entrapment within the joint space. The medial meniscus does not have a direct muscular connection. The medial meniscus may shift a few millimeters, while the less stable lateral meniscus may move at least 1 cm.In 1978, Shrive et al. reported that the collagen fibers of the menisci are oriented in a circumferential pattern. When a compressive force is applied in the knee joint, a tensile force is transmitted to the menisci. The femur attempts to spread the menisci anteroposteriorly in extension and mediolaterally in flexion. Shrive et al. further studied the effects of a radial cut in the peripheral rim of the menisci during loading. In joints with intact menisci, the force was applied through the menisci and articular cartilage; however, a lesion in the peripheral rim disrupted the normal mechanics of the menisci and allowed it to spread when a load was applied. The load now was distributed directly to the articular cartilage.
Side effects
More than 10% of people taking ledipasvir/sofosbuvir have headaches or fatigue; rashes, nausea, diarrhea, and insomnia occur in between 1% and 10% of people taking it.More severe reactions are connected with allergic reactions to the medications and cardiovascular problems. Harvoni side effects are considered relatively mild compared to older interferon-based treatment. Ledipasvir/sofosbuvir could cause hepatitis B re-activation in people co-infected with hepatitis B and C viruses. The European Medicines Agency recommended screening all people for hepatitis B before starting ledipasvir/sofosbuvir for hepatitis C in order to minimize the risk of hepatitis B reactivation. Drug interactions
Ledipasvir/sofosbuvir is a substrate for the drug transporters P-Glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Intestinal absorption of these drug transporter substrates may be decreased by inducers such as rifampin and St. Johns wort .Patients are also advised to stay away from H2 receptor antagonists (H2RA) and proton-pump inhibitors (PPI) because they decrease the concentration of ledipasvir (its solubility is pH-dependent and is higher under acidic conditions). Therefore, it is advised to take a PPI at least two hours after ledipasvir/sofosbuvir with a dose less than or equal to 20 mg daily and H2RAs with a dose of less than or equal to 40 mg twice daily.Ledipasvir/sofosbuvir should additionally be avoided when taking amiodarone or other drugs that lower heart rate; there is a serious risk of the heart slowing or stopping when ledipasvir/sofosbuvir is used with such drugs.