Stratification is required to ensure that only those patients likely to benefit, receive Autologous Chondrocyte Implantation (ACI); ideally by assessing a biomarker in the blood. This study aimed to assess differences in the plasma proteome of individuals who respond well or poorly to ACI. Isobaric tag for relative and absolute quantitation (ITRAQ) mass spectrometry and label-free proteomics analyses were performed in tandem as described previously by our group (Hulme et al., 2017; 2018; 2021) using plasma collected from ACI responders (n=10) compared with non-responders (n=10) at each stage of surgery (Stage I, cartilage harvest and Stage II, cell implantation). iTRAQ using pooled plasma detected 16 proteins that were differentially abundant at baseline in ACI responders compared with non-responders (n=10) (≥±2.0 fold; p<0.05). Responders demonstrated a mean Lysholm (patient reported functional score from 0–100) improvement of 33±13 and non-responders a mean worsening of −13±13 points. The most pronounced plasma proteome shift was seen in response to Stage I surgery in ACI non-responders, with 48 proteins being differentially abundant between the two surgical procedures. We have previously noted this marked shift in response to initial surgery in the SF of ACI non-responders, several of these proteins were associated with the Acute Phase Response. One of these proteins, clusterin, could be confirmed in patients’ plasma using an independent immunoassay using individual samples. Label-free proteomic data from individual samples identified only cartilage acidic protein-1 (known to associate with osteoarthritis progression) to be significantly more abundant at Stage I in the plasma of non-responders. This study indicates that proteins can be identified within the plasma that have potential use in ACI patient stratification. Further work is required to validate the findings of this discovery-phase work in larger ACI cohorts.
Aseptic loosening of implants following hip arthroplasty is a cause of significant patient morbidity. We genotyped 99 revision hip arthroplasty patients and 116 primary hip arthroplasty patients for the C282Y and the H63D mutations, which cause Haemochromatosis. Haemochromatosis is an inherited condition leading to excessive iron absorption and deposition in the body. All patients at the time of their primary hip arthroplasty were diagnosed as having osteoarthritis. We identified 9 of the 99 revision arthroplasty patients as being homozygous for the C282Y mutation. The time to revision in this group was significantly lower (p<
0.005) when compared to the remaining 90 patients in the group (mean 8.7 years vs 14.8 years). Analysis of variables such as patient age and sex and also type of prosthesis, place of surgery and operating surgeon had no confounding influence. We hypothesise that undiagnosed iron overload in the patients homozygous for the C282Y mutation is likely to cause premature failure of their primary hip arthroplasty.
Rheumatoid arthritis results in pain and loss of function due to gradual destruction of articular cartilage. The shoulder joint is frequently involved and a prosthetic replacement of the humeral head can restore function and relieve pain. Deficiency of the rotator cuff is common in patients with rheumatoid arthritis. Longevity of movement at the intraprosthetic interface of the bipolar shoulder prosthesis is debatable and has not previously been studied in rheumatoid arthritis. We report a radiological study of the intraprosthetic movements of a bipolar shoulder replacement in 25 shoulders in 20 patients with rheumatoid arthritis of mean age 66 years (SD 10 years). Shoulders were X-rayed at a minimum of 3 and a maximum of 10 years from surgery. Measurements were repeated in 12 shoulders 3 years later. The patient was positioned in the scapular plane. An initial X-ray was taken with the arm in neutral and a further X-ray taken with the arm in full active abduction. Measurements were taken to determine the movement at the intraprosthetic interface and at the prosthesis/glenoid interface. Interobserver error and intraobserver error were determined using an intraclass correlation coefficient (ICC). A paired T-test and Pearson Correlation Coefficient were used to compare intraprosthetic movement with prosthesis/glenoid movement. We found that intraprosthetic movement was preserved up to 10 years from surgery. However, there was no significant difference between intraprosthetic movement and shell/glenoid movement, with some shoulders exhibiting paradoxical movement at the intraprosthetic interface. Repeating the measurements after a 3 year interval in a subgroup of 12 shoulders showed a significant difference in intraprosthetic movement. Interobserver and intraobserver reliability for measurements of the movement at the intraprosthetic interface were excellent with a We conclude that movement of the bipolar shoulder prosthesis in rheumatoid shoulders at the intraprosthetic interface is preserved up to 10 years from operation but is not related to or significantly different from prosthesis/glenoid movement and requires further investigation.
The history of the development of the Kudo elbow replacement was illustrated from the original Type 1 prosthesis in 1971 to the current Type 5 manufactured in cobalt-chrone and high-density polyethylene from 1994. The results of the Kudo Trial were presented. In this prospective trial all patients had rheumatoid arthritis with at least grade 4 or grade 5 changes on the radiographs. The procedure was carried out by the same surgeon in every case using a posterior approach. The patients were reviewed at regular intervals and the results presented are of those patients at their five-year follow-up. There were 105 joints replaced in 84 patients (61 females) with an average age of 63 years. Five were revisions of previous implants. Relief of pain was very significant in all cases with only 8 patients experiencing “mild” symptons. The total gain in range of movement was 33° with 10° improvement of extension and 23° of flexion. The complication rate was low with only one patient having pronounced ulnar nerve dysaesthesia although four had a mild persistence of sensory symptoms. There were six cases of infection. Three of these were superficial with negative cultures. Three had positive cultures, all staphylococcus aureus and one of these was revised, following gentamicin beads, to a custom built prosthesis and remains clinically and radiologically satisfactory nine years later. One ulnar component became loose at five years and was satisfactorily replaced with a long stemmed pros-thesis. Radiological “lucent lines” are variably seen and their long-term significance is not fully known. A survival analysis was carried out using the method of Murray et al, which gave a 10-year survival of 86.7%.
Osteoarthritis of the hip exhibits progressive degeneration of articular cartilage frequently resulting in total hip arthroplasty (THA). Expression of cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL6) is increased in the synovium and articular cartilage of these patients. Furthermore, these cytokines have been shown to have a negative regulatory effect on chondrocyte proliferation and articular cartilage metabolism. We investigated the frequency of a G/C polymorphism at position −174 of the promoter region of the IL-6 gene and a G/A polymorphism at position −308 of the TNF alpha gene, both of which cause increased expression of these cytokines. We observed that the G variant of the IL6 gene was significantly higher in patients who had undergone revision THA compared to controls (P=0.05). It was also elevated in primary THA patients compared to controls. The G/A polymorphism in TNF alpha was not significantly associated with THA; however, this may reflect the lower incidence of this polymorphism in the population. These results suggest that an alteration in cytokine expression produced by the IL6 −174G/C mutation may have a role in the aetiology of osteoarthritis and the outcome of total hip arthroplasty.
Sixty-two cases of chondrosarcoma of bone were reviewed and histologically graded as low, medium or high-grade tumours. After excluding patients dead from unrelated causes or lost to follow-up, forty cases were available for ten-year follow-up and fifty-eight for five-year follow-up. The rates of survival, recurrence and metastasis were analysed according to the histological grading. Recurrence was further analysed according to the adequacy of treatment. The results were compared with those previously reported in the literature. There was a ten-year survival rate of 58 per cent. Recurrence developed in 58 per cent and was uncontrollable in 29 per cent. The recurrence rate was 87 per cent with inadequate treatment and 15 per cent with adequate treatment. Recurrences outside the limb bones usually proved uncontrollable; recurrences in the limb bones were amenable to further, and if necessary repeated, operations. High-grade chondrosarcoma had a metastatic risk of 75 per cent and eventual mortality of 88 per cent. Medium-grade chondrosarcoma had a metastatic risk of 14 per cent and a mortality of 60 per cent. Low-grade chondrosarcoma had a metastatic risk of 5 per cent and a mortality of 29 per cent.
