Osteoarthritis is a major source of pain, disability, and socioeconomic cost worldwide. The epidemiology of the disorder is complex and multifactorial, with genetic, biological, and biomechanical components. Aetiological factors are also joint specific. Joint replacement is an effective treatment for symptomatic end-stage disease, although functional outcomes can be poor and the lifespan of prostheses is limited. Consequently, the focus is shifting to disease prevention and the treatment of early osteoarthritis. This task is challenging since conventional imaging techniques can detect only quite advanced disease and the relation between pain and structural degeneration is not close. Nevertheless, advances in both imaging and biochemical markers offer potential for diagnosis and as outcome measures for new treatments. Joint-preserving interventions under development include lifestyle modification and pharmaceutical and surgical modalities. Some show potential, but at present few have proven ability to arrest or delay disease progression.

Knee-replacement surgery is frequently done and highly successful. It relieves pain and improves knee function in people with advanced arthritis of the joint. The most common indication for the procedure is osteoarthritis. We review the epidemiology of and risk factors for knee replacement. Because replacement is increasingly considered for patients younger than 55 years, improved decision making about whether a patient should undergo the procedure is needed. We discuss assessment of surgery outcomes based on data for revision surgery from national joint-replacement registries and on patient-reported outcome measures. Widespread surveillance of existing implants is urgently needed alongside the carefully monitored introduction of new implant designs. Developments for the future are improved delivery of care and training for surgeons and clinical teams. In an increasingly ageing society, the demand for knee-replacement surgery will probably rise further, and we predict future trends. We also emphasise the need for new strategies to treat early-stage osteoarthritis, which will ultimately reduce the demand for joint-replacement surgery.

The relationships between normal and leukemic stem/progenitor cells are unclear. We show that in ∼80% of primary human CD34+ acute myeloid leukemia (AML), two expanded populations with hemopoietic progenitor immunophenotype coexist in most patients. Both populations have leukemic stem cell (LSC) activity and are hierarchically ordered; one LSC population gives rise to the other. Global gene expression profiling shows the LSC populations are molecularly distinct and resemble normal progenitors but not stem cells. The more mature LSC population most closely mirrors normal granulocyte-macrophage progenitors (GMP) and the immature LSC population a previously uncharacterized progenitor functionally similar to lymphoid-primed multipotential progenitors (LMPPs). This suggests that in most cases primary CD34+ AML is a progenitor disease where LSCs acquire abnormal self-renewal potential.