The Dysregulated Galectin Network Activates NF-κB to Induce Disease Markers and Matrix Degeneration in 3D Pellet Cultures of Osteoarthritic Chondrocytes.

This work aimed to study the dysregulated network of galectins in OA chondrocyte pellets, and to assess whether their recently discovered activity as molecular switches of functional biomarkers results in degradation of extracellular matrix in vitro. Scaffold-free 3D pellet cultures were established of human OA chondrocytes. Expression and secretion of galectin(Gal)-1, -3, and -8 were monitored relative to 2D cultures or clinical tissue sections by RT-qPCR, immunohistochemistry and ELISAs. Exposure of 2D and 3D cultures to an in vivo-like galectin mixture (Gal-1 and Gal-8: 5 µg/ml, Gal-3: 1 µg/ml) was followed by the assessment of pellet size, immunohistochemical matrix staining, and/or quantification of MMP-1, -3, and -13. Application of inhibitors of NF-κB activation probed into the potential of intervening with galectin-induced matrix degradation. Galectin profiling revealed maintained dysregulation of Gal-1, -3, and -8 in pellet cultures, resembling the OA situation in situ. The presence of the galectin mixture promoted marked reduction of pellet size and loss of collagen type II-rich extracellular matrix, accompanied by the upregulation of MMP-1, -3, and -13. Inhibition of p65-phosphorylation by caffeic acid phenethyl ester effectively alleviated the detrimental effects of galectins, resulting in downregulated MMP secretion, reduced matrix breakdown and augmented pellet size. This study suggests that the dysregulated galectin network in OA cartilage leads to extracellular matrix breakdown, and provides encouraging evidence of the feasible inhibition of galectin-triggered activities. OA chondrocyte pellets have the potential to serve as in vitro disease model for further studies on galectins in OA onset and progression.

[Diagnostic Algorithm for Failure Analysis of Painful Total Hip Arthroplasties]. / Diagnostischer Algorithmus der schmerzhaften Hüfttotalendoprothese.

Background: Total hip arthroplasty (THA) is one of the most common and successful surgical procedures in orthopedic surgery and clinical success can be characterized by the revision rate and improvement of function, as well as the patient's satisfaction and pain. Despite the clinical success of primary THA with 10-year survival rates as high as 96 % (Swedish Hip Arthroplasty Register, 2011), the prevalence of groin pain after conventional total hip replacement ranges from 0.4 to 18.3 % and activity-limiting thigh pain is still an existing problem linked to the femoral component of uncemented hip replacement in up to 1.9 to 40.9 % of cases in some series. Obvious causes of failure might be identified with clinical examinations and standard radiographs only, whereas the unexplained painful THA still remains a challenge for the surgeon. They can be classified into extra- and intraarticular disorders, the latter being divided into biological and mechanical origins. The onset of the pain after the operation and the differentiation between pain in motion and at rest are helpful to distinguish between mechanical and non-mechanical problems. An infection should be the first diagnosis to be ruled out in a painful THA. It is generally accepted that a clear understanding of the failure mechanism in each case is required prior considering revision surgery. Method: In this review a practical diagnostic algorithm is described for failure analysis in more detail. The evaluation of a painful THA includes a detailed history with an extended analysis of the type of pain, thorough clinical examination including the spine and knee joints, radiographic and laboratory analysis, as well as invasive examinations like joint aspiration and biopsies. Conclusion: This diagnostic algorithm offers an important tool for a sufficient failure analysis in almost all patients with painful THA.

The Impact of Personality Traits on the Outcome of Total Knee Arthroplasty.

Ten to twenty percent of patients with total knee arthroplasty (TKA) are dissatisfied with their clinical outcome. Aim of this study was to investigate the impact of personality traits on the subjective outcome of TKA. We investigated 80 patients with 86 computer navigated TKAs. We asked for patients satisfaction and divided patients into two groups (satisfied or dissatisfied). 12 personality traits were tested by the Freiburg Personality Inventory (FPI-R). Postoperative examination included Knee Society Score (KSS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC), and the Visual Analogue Scale (VAS). Radiologic investigation was done in all patients. 84% of our patients were satisfied, while 16% were not satisfied. The FPI-R showed statistical significant influence of four personality traits on patient satisfaction: life satisfaction (p = 0.006), performance orientation (p = 0.015), somatic distress (p = 0.001), and emotional stability (p = 0.002). All clinical scores (VAS, WOMAC, and KSS) showed significantly better results in the satisfied patient. Radiological examination showed optimal alignment of all TKAs. There were no complications requiring revision surgery. The results of our study show that personality traits may influence patients satisfaction and clinical outcome after TKA. Therefore patients personality traits may be a useful predictive factor for postoperative satisfaction after TKA.

[A diagnostic algorithm for painful total knee replacement]. / Diagnostischer Algorithmus der schmerzhaften Knietotalendoprothese.

UNLABELLED: Total knee arthroplasty (TKA) is one of the most common procedures in orthopedic surgery and clinical success can be characterized by the revision rate and improvement of function, as well as the patients' satisfaction and pain. Despite the clinical success of primary TKA with 10-year survival rates as high as 95 %, about 20 % of the patients after TKA are not completely satisfied with their outcomes for several reasons. Obvious causes of failure might be identified with clinical examinations and standard radiographs only, whereas the unexplained painful TKA still remains a challenge for the surgeon. Failure can be classified into extra- and intraarticular disorders, the latter being divided into biological and mechanical origins. The onset of the pain after the operation and the differentiation between pain in motion and at rest are helpful to distinguish between mechanical and non-mechanical problems. An infection should be the first diagnosis to be ruled out in a painful TKA. It is generally accepted that a clear understanding of the failure mechanism in each case is required prior to considering revision surgery. METHOD: In this review a practical diagnostic algorithm is described for failure analysis in more detail. The evaluation of a painful TKA includes a detailed history with an extended analysis of the type of pain, thorough clinical examination including spine, hip and ankle, radiographic and laboratory analysis, as well as invasive examinations like joint aspiration and biopsies. CONCLUSION: This diagnostic algorithm offers an important tool for a sufficient failure analysis in almost all patients with painful TKA.

Primary cementless total hip arthroplasty with second-generation metal-on-metal bearings: a concise follow-up, at a minimum of seventeen years, of a previous report.

BACKGROUND: Second-generation, metal-on-metal bearings were introduced in 1988, to reduce wear and avoid polyethylene particle-induced osteolysis from total hip arthroplasty. In 2007, we reported the long-term results of ninety-eight patients (105 hips) who underwent primary cementless total hip arthroplasty involving the use of a prosthesis with a high-carbide-concentration, metal-on-metal articulating surface between November 1992 and May 1994. The present study gives an update on this patient cohort. METHODS: At a minimum of seventeen years postoperatively, forty-nine patients (fifty-two hips) were available for follow-up examination. We retrospectively evaluated clinical and radiographic results as well as serum metal concentration. The mean patient age at the time of the index arthroplasty was fifty-six years. RESULTS: Three cups (6% of the hips) and one stem (2% of the hips) were revised because of aseptic loosening of the implants combined with focal osteolysis. At the time of the latest follow-up evaluation, the mean Harris hip score was 88.8 points, and the mean University of California Los Angeles (UCLA) activity score was 6.7 points. The cumulative rate of implant survival, with aseptic failure as the end point, was 93.0% at 18.8 years. The median serum cobalt concentration in patients whose hip implant was the only source of cobalt was 0.70 µg/L (range, 0.4 to 5.1 µg/L), showing no increase in the value as noted at a minimum of ten years of follow-up. CONCLUSIONS: The clinical and radiographic results of our study, which, to our knowledge, represent the longest duration of follow-up for a series of cementless total hip arthroplasties with use of a 28-mm metal-on-metal bearing, continue to be comparable with the results observed for other hard-on-hard bearings.

The effect of a flexible pylon system on functional mobility of transtibial amputees. A prospective randomized study.

BACKGROUND: Prosthetic component selection strongly influences the functional mobility of transtibial amputees. Until now, little attention has been paid to the connection between the prosthetic socket and the foot component. AIM AND DESIGN: Aim of this study was to compare a novel flexible with a conventional rigid pylon system in a prospective randomized trial in transtibial amputees to determine effects on gait and mobility. SETTING: The study was performed in a rehabilitation centre for geriatric amputees. POPULATION: Twenty-eight geriatric unilateral transtibial amputees (8 female, 20 male) with low degree of mobility were included. METHODS: At admission to the rehabilitation centre objective and subjective parameters were assessed including demographic data and levels of daily activity using standardized questionnaires. Three months after prosthetic fitting a follow-up was performed and additional parameters such as walking speed, step length and vertical ground reaction forces were examined using a dynamic gait analysis. RESULTS: The study revealed a significant improvement in step length (P=0.03), in using mobility aids (P=0.04) and benefits concerning the self-selected gait speed, the mobility and gait disorders using the flexible device. CONCLUSION: The results demonstrate advantages for the flexible system, resulting in a positive effect on the patient's gait accomplishments in a geriatric population. CLINICAL REHABILITATION IMPACT: The advantages of the dynamic pylon may improve clinical rehabilitation, especially for geriatric patients with vascular disorders, as it provides comfort and better prosthetic performance during gait as a short-term benefit and thus gives a better quality of life in the long-term.