Gust Verbruggen

Transplantation of viable meniscal allograft. Survivorship analysis and clinical outcome of one hundred cases.

BACKGROUND Few medium-term or long-term reports on meniscal allograft transplantations are available. In this study, we present the results of a survival analysis of the clinical outcomes of our first 100 procedures involving transplantation of viable medial and lateral meniscal allografts performed in ninety-six patients. METHODS Thirty-nine medial and sixty-one lateral meniscal allografts were evaluated after a mean of 7.2 years. Survival analysis was based on specific clinical end points, with failure of the allograft defined as moderate occasional or persistent pain or as poor function. An additional survival analysis was performed to assess the results of the sixty-nine procedures that involved isolated use of a viable allograft (twenty of the thirty-nine medial allograft procedures and forty-nine of the sixty-one lateral allograft procedures) and of the thirteen viable medial meniscal allografts that were implanted in combination with a high tibial osteotomy in patients with initial varus malalignment of the lower limb. RESULTS Overall, eleven (28%) of the thirty-nine medial allografts and ten (16%) of the sixty-one lateral allografts failed. The mean cumulative survival time (11.6 years) was identical for the medial and lateral allografts. The cumulative survival rates for the medial and lateral allografts at ten years were 74.2% and 69.8%, respectively. The mean cumulative survival time and the cumulative survival rate for the medial allografts used in combination with a high tibial osteotomy were 13.0 years and 83.3% at ten years, respectively. CONCLUSIONS Transplantation of a viable meniscal allograft can significantly relieve pain and improve function of the knee joint. Survival analysis showed that this beneficial effect remained in approximately 70% of the patients at ten years. This study identified the need for a prospective study comparing patients with similar symptoms and clinical findings treated with and without a meniscal allograft and followed for a longer period with use of clinical evaluation as well as more objective documentation tools regarding the actual fate of the allograft itself and the articular cartilage.

Comparative study of the synovial histology in rheumatoid arthritis, spondyloarthropathy, and osteoarthritis: influence of disease duration and activity

OBJECTIVES To compare the macroscopic and microscopic characteristics of synovial tissue in rheumatoid arthritis (RA), spondyloarthropathy (SpA), and osteoarthritis (OA) after exclusion of possible biases induced by disease duration or activity, or both. METHODS Synovial biopsy specimens were obtained by needle arthroscopy in patients with early RA (n=16), late RA (n=14), early SpA (n=23), and OA (n=12). Macroscopic and microscopic features were scored on a four point scale and analysed as a function of disease duration (early versus late RA), local and systemic disease activity, and diagnosis. RESULTS Except for the maximal synovial lining thickness, no significant differences were seen between early and late RA. For disease activity, synovial histology was only weakly correlated with C reactive protein in RA, but seemed to be strongly dependent on effusion of the biopsied joint in all disease groups. After stratification for local disease activity, no disease related differences were found in patients without joint effusion. In contrast, important differences were found between patients with RA and SpA with active joint effusion. Synovial vascularity was macroscopically increased in SpA versus RA (p=0.017). A straight vessel pattern was only seen in RA, while tortuous vessels were preferentially seen in SpA. Vascularity was also microscopically increased in SpA compared with RA (p=0.031), and correlated with the macroscopic vascularity (rs =0.36, p=0.036). CD3+ (p=0.008), CD4+ (p=0.008), and CD20+ (p=0.024) lymphocytes were overrepresented in RA compared with SpA. The integrin expression in RA was characterised by a decrease of αVβ3 in the synovial lining (p=0.006) and an increase of αVβ5 in the sublining (p<0.001). CONCLUSIONS The immune architecture of the synovial membrane is more dependent on local disease activity than on disease duration. Synovium obtained from clinically affected joints shows important histological differences between RA and SpA.

Human cartilage gp-39+,CD16+ monocytes in peripheral blood and synovium: correlation with joint destruction in rheumatoid arthritis.

OBJECTIVE To investigate the expression of human cartilage (HC) gp-39, a possible autoantigen in rheumatoid arthritis (RA), in peripheral blood and synovium, to characterize its cellular source, and to analyze correlations with clinical features. METHODS The expression of HC gp-39 in synovium and peripheral blood mononuclear cells (PBMC) was assessed by immunohistochemistry and flow cytometry. Synthesis and secretion were investigated by both reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS PBMC expressing HC gp-39 were increased in RA patients compared with spondylarthropathy patients (P = 0.0029) and with healthy control subjects (P = 0.0013). HC gp-39+ cells were also slightly overrepresented in RA synovium (P = 0.01). In both blood and synovium, HC gp-39+ cells were identified as CD14dim,CD16+ monocytes, a phenotype which can differentiate from classic CD14++ monocytes by maturation in vitro. HC gp-39 messenger RNA was detected in RA synovium and PBMC, and PBMC secreted HC gp-39 in vitro. The number of HC gp-39+ PBMC correlated with serum levels of C-reactive protein (r = 0.39, P = 0.003) and HC gp-39 (r = 0.52, P = 0.014). HC gp-39 expression in RA synovial lining correlated with joint destruction (r = 0.77, P < 0.001). CONCLUSION CD16+ monocytes, a cellular source of HC gp-39 in vivo, are overrepresented in both RA peripheral blood and synovial tissue. The presence of HC gp-39+ cells in RA synovium is correlated with the degree of joint destruction. These data support a role of these cells in the local autoimmune response that leads to chronic inflammation and joint destruction.

Systemic levels of IL-23 are strongly associated with disease activity in rheumatoid arthritis but not spondyloarthritis.

Objectives Th17 cells are an effector T-cell population that plays a role in chronic inflammatory conditions and is dependent on IL-23 for their survival and expansion. More recently, a genetic association was discovered between polymorphisms in the gene coding for the IL-23 receptor and spondyloarthritis. This study aimed to evaluate the role of Th17-associated cytokines in spondyloarthritis pathogenesis by measuring their levels in the joints and circulation as well as correlating them with disease activity parameters. Methods Paired synovial fluid (SF), serum and synovial biopsies were obtained from 30 non-PsA (psoriatic arthritis) spondyloarthritis, 22 PsA and 22 rheumatoid arthritis (RA) patients. IL-17, IL-23 and CCL20 were measured by ELISA in the SF and serum of patients and correlated with systemic and local parameters of disease activity. Results Concentrations of CCL20, a major Th17-attracting chemokine, tended to be higher in the joints of RA than in spondyloarthritis patients. Interestingly, levels of CCL20 were markedly higher in SF as opposed to serum. In addition, there was a remarkable association between the expression of the Th17 cytokine system and the presence of intimal lining layer hyperplasia in RA. Also in the serum, there was a tendency for higher IL-23 levels in RA, which correlated strongly with disease activity parameters. Conclusions Th17-related cytokines are expressed in joints of spondyloarthritis as well as RA patients. IL-23 levels, however, correlate with disease activity parameters in RA only. These results point towards a differential regulation of the Th17 cytokine system in spondyloarthritis compared with RA.

Transplantation of Viable Meniscal Allograft

BACKGROUND Few medium-term or long-term reports on meniscal allograft transplantations are available. In this study, we present the results of a survival analysis of the clinical outcomes of our first 100 procedures involving transplantation of viable medial and lateral meniscal allografts performed in ninety-six patients. METHODS Thirty-nine medial and sixty-one lateral meniscal allografts were evaluated after a mean of 7.2 years. Survival analysis was based on specific clinical end points, with failure of the allograft defined as moderate occasional or persistent pain or as poor function. An additional survival analysis was performed to assess the results of the sixty-nine procedures that involved isolated use of a viable allograft (twenty of the thirty-nine medial allograft procedures and forty-nine of the sixty-one lateral allograft procedures) and of the thirteen viable medial meniscal allografts that were implanted in combination with a high tibial osteotomy in patients with initial varus malalignment of the lower limb. RESULTS Overall, eleven (28%) of the thirty-nine medial allografts and ten (16%) of the sixty-one lateral allografts failed. The mean cumulative survival time (11.6 years) was identical for the medial and lateral allografts. The cumulative survival rates for the medial and lateral allografts at ten years were 74.2% and 69.8%, respectively. The mean cumulative survival time and the cumulative survival rate for the medial allografts used in combination with a high tibial osteotomy were 13.0 years and 83.3% at ten years, respectively. CONCLUSIONS Transplantation of a viable meniscal allograft can significantly relieve pain and improve function of the knee joint. Survival analysis showed that this beneficial effect remained in approximately 70% of the patients at ten years. This study identified the need for a prospective study comparing patients with similar symptoms and clinical findings treated with and without a meniscal allograft and followed for a longer period with use of clinical evaluation as well as more objective documentation tools regarding the actual fate of the allograft itself and the articular cartilage.

A plant-derived ligand favoring monomeric glucocorticoid receptor conformation with impaired transactivation potential attenuates collagen-induced arthritis

The glucocorticoid receptor (GR) is a transcription factor regulating its target genes either positively, through direct binding to the promoter of target genes, or negatively by the interference with the activity of transcription factors involved in proinflammatory gene expression. The well-known adverse effects of glucocorticoids are believed to be mainly caused by their GR-mediated gene-activating properties. Although dimerization of GR is thought to be essential for gene-activating properties, no compound has yet been described which selectively imposes GR monomer formation and interference with other transcription factors. In the present study, we report on a GR-binding, plant-derived compound with marked dissociative properties in rheumatoid arthritis fibroblast-like synoviocytes, which are important effector cells in inflammation and matrix degradation in rheumatoid arthritis. In addition, these findings could be extended in vivo in murine collagen-induced arthritis, in which joint inflammation was markedly inhibited without inducing hyperinsulinemia. Therefore, we conclude that GR monomers are sufficient for inhibition of inflammation in vivo.

Tumour necrosis factor blockade for the treatment of erosive osteoarthritis of the interphalangeal finger joints: a double blind, randomised trial on structure modification

Background Adalimumab blocks the action of tumor necrosis factor-α and reduces disease progression in rheumatoid arthritis and psoriatic arthritis. The effects of adalimumab in controlling progression of structural damage in erosive hand osteoarthritis (HOA) were assessed. Methods Sixty patients with erosive HOA on radiology received 40 mg adalimumab or placebo subcutaneously every two weeks during a 12-month randomized double-blind trial. Response was defined as the reduction in progression of structural damage according to the categorical anatomic phase scoring system. Furthermore, subchondral bone, bone plate erosion, and joint-space narrowing were scored according to the continuous Ghent University Score System (GUSSTM). Results The disease appeared to be active since 40.0% and 26,7% of patients out of the placebo and adalimumab group, respectively, showed at least one new interphalangeal (IP) joint that became erosive during the 12 months follow-up. These differences were not significant and the overall results showed no effect of adalimumab. Risk factors for progression were then identified and the presence of palpable soft tissue swelling at baseline was recognized as the strongest predictor for erosive progression. In this subpopulation at risk, statistically significant less erosive evolution on the radiological image (3.7%) was seen in the adalimumab treated group compared to the placebo group (14.5%) (P = 0.009). GUSSTM scoring confirmed a less rapid rate of mean increase in the erosion scores during the first 6 months of treatment in patients in adalimumab-treated patients. Conclusion Palpable soft tissue swelling in IP joints in patients with erosive HOA is a strong predictor for erosive progression. In these joints adalimumab significantly halted the progression of joint damage compared to placebo.

A Pilot Study of the Use of an Osteochondral Scaffold Plug for Cartilage Repair in the Knee and How to Deal With Early Clinical Failures

PURPOSE To present our short-term experience with an osteochondral scaffold plug (TruFit plug; Smith & Nephew, Andover, MA) for cartilage repair in the knee and, more importantly, to discuss our approach to treat early clinical failures. METHODS Twenty patients were consecutively treated for their cartilage lesions with the plug technique. These patients were prospectively clinically evaluated at 6 and 12 months of follow-up. Magnetic resonance imaging (MRI) was used for morphologic analysis of the cartilage repair. Biopsy samples were taken from 3 cases during revision surgery, allowing histologic assessment of the repair tissue. RESULTS The short-term clinical and MRI outcome of this pilot study are modest. No signs of deterioration of the repair tissue were observed. Of the 15 patients followed up during 1 year, 3 (20.0%) showed persistent clinical symptoms or even more clinical symptoms after insertion of the plug. These patients were considered as failures and therefore eligible for revision surgery. During revision surgery, the repair tissue was carefully removed. The remaining osteochondral defect was filled with autologous bone grafts. Immediate and persistent relief of symptoms was observed in all 3 patients. Histologic assessment of biopsy specimens taken during revision surgery showed fibrous vascularized repair tissue with the presence of foreign-body giant cells. CONCLUSIONS The overall short-term clinical and MRI outcome of the osteochondral scaffold plug for cartilage repair in the knee is modest. In this pilot study a modest clinical improvement became apparent at 12 months of follow-up. MRI data showed no deterioration of the repair tissue. Of the 15 patients, 3 (20%) had persistent clinical symptoms after surgery. These patients were successfully treated with removal of the osteochondral plug remnants and the application of autologous bone grafts. LEVEL OF EVIDENCE Level IV, therapeutic case series.

Silkworm and spider silk scaffolds for chondrocyte support.

Objective To create scaffolds with silkworm cocoon, spider egg sac and spider dragline silk fibres and examine their use for chondrocyte attachment and support. Methods Three different kinds of scaffolds were developed with Bombyx mori cocoon, Araneus diadematus egg sac and dragline silk fibres. The attachment of human articular cartilage cells were investigated on these bioprotein matrices. The chondrocytes produced an extracellular matrix which was studied by immunostaining. Moreover, the compression behaviour in relation to the porosity was studied. Results The compression modulus of a silkworm silk scaffold was related to its porosity. Chondrocytes were able to attach and to grow on the different fibres and in the scaffolds for several weeks while producing extracellular matrix products. Conclusion Porous scaffolds can be made out of silkworm and spider silk for cartilage regeneration. Mechanical properties are related to porosity and pore size of the construct. Cell spreading and cell expression depended on the porosity and pore-size.

Treatment of Cartilage Defects in the Knee Using Alginate Beads Containing Human Mature Allogenic Chondrocytes

Background The repair of osteochondral lesions is imperfect and transient; chondral lesions do not heal in mature cartilage. Attempts have been made to restore cartilage lesions by filling the defects with a temporary artificial biocompatible matrix. Purpose To determine whether the implantation of alginate beads containing human mature allogenic chondrocytes is feasible and safe for the treatment of symptomatic cartilage defects in the knee. Study Design Case series; Level of evidence, 4. Methods A biodegradable, alginate-based, biocompatible scaffold containing human mature allogenic chondrocytes was used for the treatment of chondral and osteochondral lesions in the knee. Twenty-one patients were clinically and prospectively evaluated with use of the Western Ontario and McMaster Universities Osteoarthritis Index and a visual analog scale for pain preoperatively and at 3, 6, 9, 12, 18, and 24 months of follow-up. Of the 21 patients, 13 consented to having a biopsy sample taken for investigative purposes from the area of implantation at 12 months of follow-up, allowing histologic assessment of the repair tissue. Results A statistically significant clinical improvement became apparent after 6 months, and patients improved during the 24 months of follow-up. Adverse reactions to the alginate/fibrin matrix seeded with the allogenic cartilage cells were not observed. Histologic analysis of the biopsy specimens rated the repair tissue as hyaline-like in 15.3% of the samples, as mixed tissue in 46.2%, as fibrocartilage in 30.8%, and as fibrous in 7.7%. Conclusion The results of this short-term pilot study show that the alginate-based scaffold containing human mature allogenic chondrocytes is feasible and safe for the treatment of symptomatic cartilage defects of the knee. The described technique provides clinical and histologic outcomes that are equal but not superior to those of other cartilage repair techniques.