Puyi Sheng

Revision Total Knee Arthroplasty: 1990 Through 2002

BACKGROUND National and regional arthroplasty registries have been used to study the results of primary total knee arthroplasties. The purpose of this paper was to present the results of revision total knee replacements and describe predictors of survival of those replacements, with repeat revision as the end point. METHODS The nationwide Finnish Arthroplasty Registry included 2637 revision total knee arthroplasties from 1990 through 2002. Survivorship of the revision total knee arthroplasties was analyzed, with repeat revision as the end point. The survivorship analyses comprised evaluations of the proportional hazards assumption followed by calculations of univariate and multivariate statistics and model diagnostics as appropriate. RESULTS The survival rate following the revision total knee arthroplasties was 95% (95% confidence interval, 94% to 96%) at two years (1874 knees), 89% (95% confidence interval, 88% to 90%) at five years (944 knees), and 79% (95% confidence interval, 78% to 81%) at ten years (141 knees). Multivariate regression analysis showed the most significant predictors of prosthetic survival to be the age of the patient and the life in service of the primary total knee replacement (that is, the time between the primary total knee replacement and the revision). Survivorship was also significantly predicted by the year of the first revision total knee arthroplasty and the reason for the revision. CONCLUSIONS An age greater than seventy years, revision five years or more after the primary arthroplasty, and absence of patellar subluxation are positive indicators of survival of a revision total knee replacement. We believe that normal aging as well as the deconditioning effect of disease (osteoarthritis and rheumatoid arthritis) and its treatment (primary total knee replacement) may lead to a reduced activity level, which, together with a presumed reluctance to operate on elderly patients, protects against repeat revisions. LEVEL OF EVIDENCE Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.

Spacer prostheses in two-stage revision of infected knee arthroplasty.

At present, no consensus exists on the best spacer alternative for the management of two-stage exchange arthroplasty of infected knee arthroplasties. In this retrospective study, patient records of 24 patients, who had undergone two-stage revisions in which resterilised prosthetic components were used as spacers, were reviewed. The outcome was compared to that of operations performed during the same period (1993–2003) using cement spacers (n=10). With an average follow-up of 32 months, control of infection was achieved in 26 cases (76%), with good or excellent clinical outcome in 19 cases (56%). Treatment failed and resulted in amputation at the level of the thigh before reimplantation in one case. Three patients did not undergo reimplantation. In four cases (12%) infection relapsed. The reinfection rate did not differ between the two spacer groups. Patients treated with resterilised components had a superior range of motion during the period between the two stages. Operative time was shorter and there was less blood loss in the reimplantation arthroplasty when a prosthetic spacer was used. We consider resterilised prosthetic components a safe and effective alternative to cement spacers in the management of infected knee arthroplasties.RésuméIl n’existe pas actuellement de consensus sur les meilleurs spacers à utiliser dans le traitement des reprises en deux temps des prothèses totales du genou infectées. Dans cette étude rétrospective, 24 patients ont été évalués, patients ayant bénéficié d’un changement prothétique en deux temps, le spacer utilisé pouvant être les composants prothétiques stérilisés. Nous avons comparé le devenir de cette série (1993–2003) à une autre série traitée pendant la même période et en utilisant un spacer en ciment (10 patients). Le délai moyen était de 32 mois et la guérison de l’infection a été obtenue dans 76% des cas (26) avec un excellent ou un bon résultat dans 19 cas (56%). Les échecs du traitement sont secondaires à une amputation de cuisse avant la réimplantation (un cas). Trois patients n’ont pas eu de réimplantation et dans 4 cas (12%) l’infection a récidivé. La récidive de l’infection n’est pas différente entre les deux groupes de patients quelle que soit la nature du spacer. Les patients traités avec des composants prothétiques re-stérilisés ont eu une meilleure mobilité pendant la période intermédiaire. Le temps opératoire et les pertes sanguines sont significativement diminués lorsque le spacer utilisé est la prothèse re-stérilisée. Nous considérons en conclusion, que la re-stérilisation du composant prothétique est une méthode sure, efficace et une bonne alternative au spacer en ciment lors du traitement des prothèses totales du genou infectées.

Patient outcome following revision total knee arthroplasty: a meta-analysis

The purpose of this study was to summarize the literature describing patient outcome following revision total knee arthroplasty. Original studies were included if they were published between 1990 and 2002, enrolled ten or more patients, and measured patient outcome using a global knee rating scale. We found 33 studies with a total number of 1,356 patients. There were 429 men and 611 women with a mean age of 67 (45–90) years. The weighted mean follow-up time was 57 (6–108) months. The main indication of revision was loosening. The weighted mean preoperative and postoperative knee scores were 49 (15–82) and 84 (58–109) respectively. There were significant differences between preoperative and postoperative knee and function scores and motion (knee: t=12.507 p<0.001, function: t=4.704 p<0.001, motion: t=5.346 p<0.001). Loosening was also the main complication after revision surgery. In this analysis, revision total knee arthroplasty was a safe and effective procedure.RésuméLe but de cette étude était de résumer la littérature qui décrit les résultats après reprise d’arthroplastie totale du genou. Les études originales ont été incluses si elles avaient été publiés entre 1990 et 2002, avec dix malades au moins et l’utilisation d’une échelle d’appréciation globale du genou. Nous avons trouvé 33 études avec un nombre total de 1356 malades. Il y avait 429 hommes et 611 femmes avec un âge moyen de 67 (45–90) années. La moyenne pondéré de suivi était 57 (6–108) mois. La principale indication pour la révision était le descellement. Les scores moyens pondérés préopératoires et les scores postopératoires étaient 49 (15–82) et 84 (58–109) respectivement. Il y avait des différences significatives entre les scores du genou pré - et postopératoires, les scores fonctionnels et les scores d’amplitude (score du Genou: t=12.507 p<0.001, scores fonctionnels: t=4.704 p<0.001, scores d’amplitude: t=5.346 p<0.001). Le descellement était aussi la principale complication après la chirurgie de révision. La révision de l’arthroplastie totale du genou était une procédure sûre et efficace dans ces études.

The Role of MicroRNA-381 in Chondrogenesis and Interleukin-1-β Induced Chondrocyte Responses.

Aim: The molecular pathways regulating cartilage degradation are unclear. miR-381 was identified as a putative regulator of chondrogenesis related genes. Here, we examined its role in chondrogenesis and osteoarthritic cartilage degeneration. Methods: miR-381 expression was assessed in vitro in response to IL-1β stimulation in primary human (PHC) and mouse (PMC) chondrocytes, and ATDC5 derived chondrocytes; and in vivo in mouse embryos and human osteoarthritic cartilage. The effects of miR-381 on chondrogenesis and NF-kB signaling were assessed using a synthetic RNA mimic or inhibitor and luciferase assay, respectively. Upstream regulators of miR381 were probed using siRNA or overexpression plasmids for Sox9 and Runx2. Results: miR-381 expression was elevated in chondrogenic and hypertrophic ATDC5 cells. miR-381 was induced in vitro by IL-1β in ATDC5 cells, PMCs, and PHCs, and was expressed in areas of cartilage degradation or absorption in vivo. Overexpression of Runx2 or Sox9 increased miR-381 expression in ATDC5 cells. miR-381 suppressed expression of collagen, type II, alpha 1, and enhanced expression of metalloproteinase-13 (MMP-13), but did not regulate NFKBIA and NKRF activity. Conclusion: miR-381 was highly expressed during chondrogenesis and in arthritic cartilage. It may contribute to absorption of the cartilage matrix by repressing type II collagen and inducing MMP-13.

Revision total knee arthroplasty with the Total Condylar III system: A comparative analysis of 71 consecutive cases of osteoarthritis or inflammatory arthritis

Background As revision total knee arthroplasty surgery is becoming more common, it is necessary to evaluate how individual revision prosthesis systems perform in degenerative and inflammatory arthritides. In this study, results of the use of the Total Condylar III (TC III) system in osteoarthritis (55 knees) were compared to results of its use in inflammatory arthritis (16). Methods Patients were followed radiographically for 5.9 (3.0–10.2) years and clinically for 3.0 (0.2–6.8) years, using re-revision as the endpoint. Results At 1 year after revision and at final follow-up, the total Knee Society knee score, function score and range of motion had improved (p < 0.001) with no differences between osteoarthritis and inflammatory arthritis. No knee had definite component loosening, although 23 knees had asymptomatic radiolucent lines. Complications comprised 4 infections, 1 patellar pain syndrome and 1 rupture of the patellar tendon. Using any re-revi-sion of the prosthesis as the endpoint, 5-year survival was 95% and 8-year survival was 94%. Interpretation Concentration of demanding revision knee arthroplasties to a few hands led to good or excellent knee joint knee score results in four-fifths of the patients, and showed good outcome with the TCIII system. In spite of ligamentous laxity, propensity to develop infections, bone destruction and poor general health, patients with inflammatory arthritis had results similar to those with osteoarthritis.

MicroRNA-381 Regulates Chondrocyte Hypertrophy by Inhibiting Histone Deacetylase 4 Expression.

Chondrocyte hypertrophy, regulated by Runt-related transcription factor 2 (RUNX2) and matrix metalloproteinase 13 (MMP13), is a crucial step in cartilage degeneration and osteoarthritis (OA) pathogenesis. We previously demonstrated that microRNA-381 (miR-381) promotes MMP13 expression during chondrogenesis and contributes to cartilage degeneration; however, the mechanism underlying this process remained unclear. In this study, we observed divergent expression of miR-381 and histone deacetylase 4 (HDAC4), an enzyme that directly inhibits RUNX2 and MMP13 expression, during late-stage chondrogenesis of ATDC5 cells, as well as in prehypertrophic and hypertrophic chondrocytes during long bone development in E16.5 mouse embryos. We therefore investigated whether this miRNA regulates HDAC4 expression during chondrogenesis. Notably, overexpression of miR-381 inhibited HDAC4 expression but promoted RUNX2 expression. Moreover, transfection of SW1353 cells with an miR-381 mimic suppressed the activity of a reporter construct containing the 3′-untranslated region (3′-UTR) of HDAC4. Conversely, treatment with a miR-381 inhibitor yielded increased HDAC4 expression and decreased RUNX2 expression. Lastly, knockdown of HDAC4 expression resulted in increased RUNX2 and MMP13 expression in SW1353 cells. Collectively, our results indicate that miR-381 epigenetically regulates MMP13 and RUNX2 expression via targeting of HDAC4, thereby suggesting the possibilities of inhibiting miR-381 to control chondrocyte hypertrophy and cartilage degeneration.

IRAK-M in macrophages around septically and aseptically loosened hip implants†

The most common long-term complication of joint arthroplasty is loosening, which is mediated by chronic inflammatory cytokines produced by macrophages stimulated by implant-derived debris and eventually bacterial components adherent to such debris. In this study, antiinflammatory interleukin-1 receptor-associated kinase-M (IRAK-M) was studied in macrophages in interface membranes in vivo using immunohistochemical staining and in titanium particle-stimulated macrophages in vitro using reverse transcriptase-polymerase chain reaction. Results show that the interface membranes of septically and aseptically loosened prosthesis express more IRAK-M protein than control membranes from osteoarthritic patient and that IRAK-M mRNA-levels increase upon particle stimulation. These findings suggest that, the upregulation of IRAK-M in macrophages is involved in the local immunosuppression around implants, and may contribute to septic and aseptic implant loosening.

Revision total knee arthroplasty with the Total Condylar III system in inflammatory arthritis

We report a consecutive series of 16 revision total knee arthroplasties using the Total Condylar III system in 14 patients with inflammatory arthritis which were performed between 1994 and 2000. There were 11 women and three men with a mean age of 59 years (36 to 78). The patients were followed up for 74 months (44 to 122). The mean pre-operative Knee Society score of 37 points (0 to 77) improved to 88 (61 to 100) at follow-up (t-test, p < 0.001) indicating very good overall results. The mean range of flexion improved from 62 degrees (0 degrees to 120 degrees) to 98 degrees (0 degrees to 145 degrees) (t-test, p < 0.05) allowing the patients to stand from a sitting position. The mean Knee Society pain score improved from 22 (10 to 45) to 44 (20 to 50) (t-test, p < 0.05). No knee had definite loosening, although five showed asymptomatic radiolucent lines. Complications were seen in three cases, comprising patellar pain, patellar fracture and infection. These results suggest that the Total Condylar III system can be used successfully in revision total knee arthroplasty in inflammatory arthritis.

Resveratrol Protects against Titanium Particle-Induced Aseptic Loosening Through Reduction of Oxidative Stress and Inactivation of NF-κB

Aseptic implant loosening is closely associated with chronic inflammation induced by implant wear debris, and reactive oxygen species (ROS) play an important role in this process. Resveratrol, a plant compound, has been reported to act as an antioxidant in many inflammatory conditions; however, its protective effect and mechanism against wear particle-induced oxidative stress remain unknown. In this study, we evaluated resveratrol’s protective effects against wear particle-induced oxidative stress in RAW 264.7 macrophages. At non-toxic concentrations, resveratrol showed dose-dependent inhibition of nitric oxide (NO) production, ROS generation, and lipid peroxidation. It also downregulated the gene expression of oxidative enzymes, including inducible nitric oxide synthase (iNOS) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX)-1 and NOX-2, and promoted the gene expression and activities of antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx). This protective effect against wear particle-induced oxidative stress was accompanied by a reduction of gene expression and release of tumor necrosis factor-α (TNF-α), and decreased gene expression and phosphorylation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). These findings demonstrate that resveratrol can inhibit wear particle-induced oxidative stress in macrophages, and may exert its antioxidant effect and protect against aseptic implant loosening.

Wear Particles Promote Reactive Oxygen Species-Mediated Inflammation via the Nicotinamide Adenine Dinucleotide Phosphate Oxidase Pathway in Macrophages Surrounding Loosened Implants

Background/Aims: Prosthesis loosening is closely associated with chronic inflammatory cytokine secretion by macrophages, which are activated by wear particles or inflammatory stimulants such as lipopolysaccharide (LPS). Reactive oxygen species (ROS) are critical regulators of inflammation, but their enzymatic sources in response to wear particles and their effects on peri-implant LPS-tolerance remain unclear. Methods: Three ROS-related enzymes—nicotinamide adenine dinucleotide phosphate oxidase (NOX)-1 and -2 and catalase—were investigated in interface membrane tissues and in titanium (Ti) particle-stimulated macrophages in vitro. The generation of ROS and downstream inflammatory effects were measured with or without pre-incubation with apocynin, an NOX inhibitor. Results: Pre-exposure to Ti particles attenuated NF-κB activation in LPS-stimulated macrophages, indicating that wear particles suppress immune response, which may lead to chronic inflammation. NOX-1 and -2 were highly expressed in aseptically loosened interface membranes and in macrophages stimulated with Ti particles; the particles induced a moderate amount of ROS generation, NF-κB activation, and TNF-a secretion in macrophages, and these effects were suppressed by apocynin. Conclusion: Wear particles induce ROS generation through the NOX signaling pathway, resulting in persistent inflammation and delayed loosening. Thus, the suppression of NOX activity may be a useful strategy for preventing prosthesis loosening.