Preliminary results of a phase II randomized study to determine the efficacy and safety of genetically engineered allogeneic human chondrocytes expressing TGF-ß1 in patients with grade 3 chronic degenerative joint disease of the knee.

OBJECTIVE: The aim of this study was to preliminarily evaluate the efficacy and outcomes of injectable genetically engineered chondrocytes virally transduced with TGF-ß1 (GEC-TGF-ß1) compared to placebo. DESIGN: A multi-center, double-blinded, placebo-controlled, randomized study of adults with knee osteoarthritis. A total of 102 patients were 2:1 randomized to GEC-TGF-ß1 or placebo. Primary outcomes assessed were (1) function of the knee joint, scored using the International Knee Documentation Committee (IKDC); and (2) pain, measured by Visual Analog Scale (VAS). Secondary endpoints assessed were pain and analgesic use, quality of life (QOL), and adverse events (AEs) including need for total knee arthroplasty after treatment. RESULTS: IKDC showed significant improvement in the GEC-TGF-ß1 group over the placebo at week 12 (least mean square difference (LSMD): 10.3; P = 0.0342), week 52 (LSMD: 13.6; P = 0.0082), and overall (LSMD: 8.6; P = 0.0453). VAS Analysis showed a significant improvement in GEC-TGF-ß1 group compared to placebo at weeks 12 (LSMD: -13.8; P = 0.0162), 52 (LSMD: -13.1; P = 0.0332), and overall (LSMD: -10.1; P = 0.0350). Reduction in pain severity at week 12 and 52, frequency at 24 h and week 52, and the percentage of patients in the GEC-TGF-ß1 group receiving analgesics at week 4 (27 vs 40%) and 12 (27 vs 37%) was observed. CONCLUSIONS: GEC-TGF-ß1 patients had more positive responses on the IKDC, VAS, and were less likely to require analgesics. TRIAL NUMBER: ClinicalTrials.gov (NCT01221441) - "Study of TG-C in Patients with Grade 3 Degenerative Joint Disease of the Knee".

Total hip arthroplasty after fracture of the acetabulum. Long-term results.

We made a retrospective study of 55 primary total hip arthroplasties in 53 patients with a history of previous acetabular fracture. The mean follow-up was 7.5 years and the average age at fracture was 48.7 years. The incidence of radiographic femoral loosening (29.4%), symptomatic loosening (15.7%), and femoral revision (7.8%) were similar to those previously reported at 10 years for routine arthroplasties by Stauffer (1982). On the acetabular side, the incidence of radiographic loosening (52.9%), symptomatic loosening (27.5%), and revision (13.7%) were four to five times higher. We conclude that a history of prior acetabular fracture has a significant adverse impact on the long-term outcome of any subsequent total hip arthroplasty.

The role of continuous passive motion following total knee arthroplasty.

A retrospective study of 94 knees with postoperative continuous passive motion (CPM) therapy was compared with a control group of 116 knees with no postoperative CPM following kinematic condylar total knee arthroplasty (TKA) performed in 1983. The diagnoses were similar in both groups, with osteoarthritis in 167 knees, rheumatoid arthritis in 34 knees, osteonecrosis in four knees, traumatic arthritis in four knees, and psoriatic arthritis in one knee. Average flexion at hospital discharge was 87.7 degrees in the control group and 90.2 degrees in the CPM group (p less than 0.02). Seventy-four percent of the CPM group and 60% of the control group had achieved 90 degrees of flexion by the time of hospital discharge. The number of days to achieve 90 degrees averaged 10.3 in the control group and 7.7 in the CPM group (p less than 0.001). There was no significant difference in flexion at two or three months or at one year after operation between the two groups. Five knees in the control group and one in the CPM group required manipulation. The duration of hospitalization was not significantly different between the two groups. Hemoglobin levels, operative blood loss, and transfusion requirements were not significantly different. Patients with CPM following TKA achieve motion earlier than those without CPM, but ultimate motion and complications are not affected.

Arthrodesis for failed ankle arthroplasty.

Thirty-eight ankles in 36 patients who underwent fusion for failed total ankle arthroplasty were reviewed. Twenty-two patients were women and 14 were men, and their mean age was 56.8 years. The fusion methods performed in the 38 ankles were malleolar resection in 13, intercalated bone graft in 20, and posterior tibiotalocalcaneal fusion in 5. Fixation was external in 36 ankles and internal in 2. Bone graft was used in 32 ankles. Union was achieved in 33 ankles (89%). The average duration of the follow-up period in 29 patients (31 ankles) was 8.3 years (range, 2-14.4 years). Patients had no or mild pain in 24 ankles (80%). Complications occurred in five ankles (13%). Failed total ankle arthroplasty may be successfully salvaged by arthrodesis.

Total knee arthroplasty in patients with prior ipsilateral hip fusion.

Sixteen total knee arthroplasties performed between 1977 and 1985 in 13 patients with prior ipsilateral hip arthrodesis or ankylosis were studied to determine the preferred sequence and long-term follow-up of procedures in this clinical setting. Twelve of 16 underwent fusion takedown and total hip arthroplasty prior to knee replacement. The average age at total knee arthroplasty was 52.7 years and the average time from hip fusion to total knee arthroplasty was 36.3 years. Mean follow-up after total knee arthroplasty was 5.5 years (range, 2.3 to 10 years). The Hospital for Special Surgery knee score increased from a mean of 31.8 preoperatively to 72.2 after surgery. In patients who had conversion of the hip fusion prior to knee replacement, knee scores were 28 before and 72.5 after both procedures. Patients who retained their hip fusion had mean scores of 43.5 and 72.1, respectively. None of the knees has been removed and 14 of 16 had no pain at last follow-up. One had mild pain and one had moderate pain attributed to pes anserine bursitis. Although the numbers are small, this experience reveals that takedown of the fusion with total hip arthroplasty is an effective technique before performing the knee replacement. Though successful in some instances, the experience is too small to show that if hip fusion is in good position, knee replacement without fusion takedown is acceptable.