A J Price

Coexistence of LMPP-like and GMP-like Leukemia Stem Cells in Acute Myeloid Leukemia

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.

Transferring simulated arthroscopic skills to the operating theatre: a randomised blinded study.

The aim of this study was to investigate the effect of laboratory-based simulator training on the ability of surgical trainees to perform diagnostic arthroscopy of the knee. A total of 20 junior orthopaedic trainees were randomised to receive either a fixed protocol of arthroscopic simulator training on a bench-top knee simulator or no additional training. Motion analysis was used to assess performance objectively. Each trainee then received traditional instruction and demonstrations of diagnostic arthroscopy of the knee in theatre before performing the procedure under the supervision of a blinded consultant trainer. Their performance was assessed using a procedure-based assessment from the Orthopaedic Competence Assessment Project and a five-point global rating assessment scale. In theatre the simulator-trained group performed significantly better than the untrained group using the Orthopaedic Competence Assessment Project score (p = 0.0007) and assessment by the global rating scale (p = 0.0011), demonstrating the transfer of psychomotor skills from simulator training to arthroscopy in the operating theatre. This has implications for the planning of future training curricula.

Temporal trends in hip and knee replacement in the United Kingdom: 1991 TO 2006

Using the General Practice Research Database, we examined the temporal changes in the rates of primary total hip (THR) and total knee (TKR) replacement, the age at operation and the female-to-male ratio between 1991 and 2006 in the United Kingdom. We identified 27 113 patients with THR and 23 843 with TKR. The rate of performance of THR and TKR had increased significantly (p < 0.0001 for both) during the 16-year period and was greater for TKR, especially in the last five years. The mean age at operation was greater for women than for men and had remained stable throughout the period of study. The female-to-male ratio was higher for THR and TKR and had remained stable. The data support the notion that the rate of joint replacement is increasing in the United Kingdom with the rate of TKR rising at the highest rate. The perception that the mean age for TKR has decreased over time is not supported.

A mobile-bearing total knee prosthesis compared with a fixed-bearing prosthesis: A MULTICENTRE SINGLE-BLIND RANDOMISED CONTROLLED TRIAL

Before proceeding to longer-term studies, we have studied the early clinical results of a new mobile-bearing total knee prosthesis in comparison with an established fixed-bearing device. Patients requiring bilateral knee replacement consented to have their operations under one anaesthetic using one of each prosthesis. They also agreed to accept the random choice of knee (right or left) and to remain ignorant as to which side had which implant. Outcomes were measured using the American Knee Society Score (AKSS), the Oxford Knee Score (OKS), and determination of the range of movement and pain scores before and at one year after operation. Preoperatively, there was no systematic difference between the right and left knees. One patient died in the perioperative period and one mobile-bearing prosthesis required early revision for dislocation of the meniscal component. At one year the mean AKSS, OKS and pain scores for the new device were slightly better (p < 0.025) than those for the fixed-bearing device. There was no difference in the range of movement. We believe that this is the first controlled, blinded trial to compare early function of a new knee prosthesis with that of a standard implant. It demonstrates a small but significant clinical advantage for the mobile-bearing design.

Unnecessary contraindications for mobile-bearing unicompartmental knee replacement

The contraindications for unicompartmental knee replacement (UKR) remain controversial. The views of many surgeons are based on Kozinn and Scotts 1989 publication which stated that patients who weighed more than 82 kg, were younger than 60 years, undertook heavy labour, had exposed bone in the patellofemoral joint or chondrocalcinosis, were not ideal candidates for UKR. Our aim was to determine whether these potential contraindications should apply to patients with a mobile-bearing UKR. In order to do this the outcome of patients with these potential contraindications was compared with that of patients without the contraindications in a prospective series of 1000 UKRs. The outcome was assessed using the Oxford knee score, the American Knee Society score, the Tegner activity score, revision rate and survival. The clinical outcome of patients with each of the potential contraindications was similar to or better than those without each contraindication. Overall, 678 UKRs (68%) were performed in patients who had at least one potential contraindication and only 322 (32%) in patients deemed to be ideal. The survival at ten years was 97.0% (95% confidence interval 93.4 to 100.0) for those with potential contraindications and 93.6% (95% confidence interval 87.2 to 100.0) in the ideal patients. We conclude that the thresholds proposed by Kozinn and Scott using weight, age, activity, the state of the patellofemoral joint and chondrocalcinosis should not be considered to be contraindications for the use of the Oxford UKR.

Hamstrings vs. patella tendon for anterior cruciate ligament reconstruction: a randomised controlled trial.

A randomised controlled trial was performed to evaluate early outcome for two types of anterior cruciate ligament reconstruction. Sixty patients undergoing cruciate reconstruction were randomized into two groups. Group PT underwent reconstruction using a patella tendon autograft, whereas Group (SG) had a semitendinosus/gracilis autograft (SG). IKDC, Lysholm, and Tegner scores, KT1000 values and muscle strength were recorded pre-operatively, at 6 months and 1 year follow up. The functional scores, activity level, muscle strength and anterior tibial translation improved in both groups. No significant difference between groups was found for any measurement at 6 months and 1 year despite adequate study power. The study indicates that the 1 year results for either technique are equally favourable.

A mobile-bearing total knee prosthesis compared with a fixed-bearing prosthesis

Before proceeding to longer-term studies, we have studied the early clinical results of a new mobile-bearing total knee prosthesis in comparison with an established fixed-bearing device. Patients requiring bilateral knee replacement consented to have their operations under one anaesthetic using one of each prosthesis. They also agreed to accept the random choice of knee (right or left) and to remain ignorant as to which side had which implant. Outcomes were measured using the American Knee Society Score (AKSS), the Oxford Knee Score (OKS), and determination of the range of movement and pain scores before and at one year after operation. Preoperatively, there was no systematic difference between the right and left knees. One patient died in the perioperative period and one mobile-bearing prosthesis required early revision for dislocation of the meniscal component. At one year the mean AKSS, OKS and pain scores for the new device were slightly better (p < 0.025) than those for the fixed-bearing device. There was no difference in the range of movement. We believe that this is the first controlled, blinded trial to compare early function of a new knee prosthesis with that of a standard implant. It demonstrates a small but significant clinical advantage for the mobile-bearing design.

The incidence of physiological radiolucency following Oxford unicompartmental knee replacement and its relationship to outcome

Narrow, well-defined radiolucent lines commonly observed at the bone-implant interface of unicompartmental knee replacement tibial components have been referred to as physiological radiolucencies. These should be distinguished from pathological radiolucencies, which are poorly defined, wide and progressive, and associated with loosening and infection. We studied the incidence and clinical significance of tibial radiolucent lines in 161 Oxford unicondylar knee replacements five years after surgery. All the radiographs were aligned with fluoroscopic control to obtain views parallel to the tibial tray to reveal the tibial bone-implant interface. We found that 49 knees (30%) had complete, 52 (32%) had partial and 60 (37%) had no radiolucent lines. There was no relationship between the incidence of radiolucent lines and patient factors such as gender, body mass index and activity, or operative factors including the status of the anterior cruciate ligament and residual varus deformity. Nor was any statistical relationship established between the presence of radiolucent lines and clinical outcome, particularly pain, assessed by the Oxford Knee score and the American Knee Society score. We conclude that radiolucent lines are common after Oxford unicompartmental knee replacement but that their aetiology remains unclear. Radiolucent lines were not a source of adverse symptoms or pain. Therefore, when attempting to identify a source of postoperative pain after Oxford unicompartmental knee replacement the presence of a physiological radiolucency should be ignored.

Dislocation of the bearing of the Oxford lateral unicompartmental arthroplasty. A radiological assessment.

When the Oxford unicompartmental meniscal bearing arthroplasty is used in the lateral compartment of the knee, 10% of the bearings dislocate. A radiological review was carried out to establish if dislocation was related to surgical technique. The postoperative radiographs of 46 lateral unicompartmental arthroplasties were analysed. Five variables which related to the position and alignment of the components were measured. Dislocations occurred in six knees. Only one of the five variables, the proximal tibial varus angle, had a statistically significant relationship to dislocation. This variable quantifies the height of the lateral joint line. The mean proximal tibial varus angle for knees the bearings of which had dislocated was 9 degrees and for those which had not it was 5 degrees. In both groups it was greater than would be expected in the normal knee (3 degrees). Our study suggests that a high proximal tibial varus angle is associated with dislocation. The surgical technique should be modified to account for this, with care being taken to avoid damage to or overdistraction of the lateral soft tissues.

The effects of age on patient-reported outcome measures in total knee replacements

We present a comparison of patient-reported outcomes (PROMs) in relation to patient age, in patients who had received a total (TKR) or unicompartmental knee replacement (UKR). The outcome was evaluated using the Oxford knee score (OKS), EuroQol (EQ-5D) and satisfaction scores. Patients aged 65 to 84 years demonstrated better pre-operative function scores than those aged < 65 years (OKS, p = 0.03; EQ-5D, p = 0.048) and those aged ≥ 85 years (OKS, p = 0.03). Post-operative scores were comparable across age groups, but a linear trend for greater post-operative improvement in OKS and EQ-5D was seen with decreasing age (p < 0.033). The overall mean satisfaction score at six months was 84.9, but those aged < 55 years exhibited a lower mean level of satisfaction (78.3) compared with all other age groups (all p < 0.031). The cumulative overall two-year revision rate was 1.3%. This study demonstrates that good early outcomes, as measured by the OKS and EQ-5D, can be anticipated following knee replacement regardless of the patients age, although younger patients gain greater improvement. However, the lower satisfaction in those aged < 55 years is a concern, and suggests that outcome is not fully encapsulated by the OKS and EQ-5D evaluation, and raises the question whether the OKS alone is an appropriate measure of pain and function in younger, more active individuals.