Online Videos Regarding Relevant Postoperative Patient Information and Postoperative Rehabilitation After Arthroscopic Rotator Cuff Repair Provide Poor Information Quality, Accuracy, and Reliability.

PURPOSE: To evaluate the information quality, accuracy, and reliability of YouTube videos regarding relevant postoperative patient information and postoperative rehabilitation after arthroscopic rotator cuff repair. METHODS: By use of The Onion Router (TOR) software and predefined search terms, 102 videos were assessed. Four scoring systems were used to evaluate included videos: (1) Journal of the American Medical Association (JAMA) benchmark criteria score; (2) Global Quality Score (GQS); (3) DISCERN score; and (4) a newly developed score, the Rotator Cuff Score (RCS). The RCS (0-30 points) was built based on the latest published evidence and guidelines from the American Academy of Orthopaedic Surgeons. Videos that scored up to 9 points were regarded as poor-quality videos. RESULTS: Most of the included videos provided poor information quality, accuracy, and reliability. Videos that were uploaded by medically trained professionals showed significantly better results for all scores compared with commercial or personal-testimony videos (JAMA benchmark criteria score, P < .001; GQS, P < .001; DISCERN score, P = .001; and RCS, P = .001). Multivariate linear regression showed that the involvement of medically trained professionals was a significant predictor of better results for all scores (JAMA benchmark criteria score, ß = 1.496 [P < .001]; GQS, ß = 1.105 [P < .001]; DISCERN score, ß = 11.234 [P < .001]; and RCS, ß = 5.017 [P < .001]). Surprisingly, the like ratio was significantly higher for videos that were uploaded by non-medically trained individuals (P = .041). CONCLUSIONS: The average information quality, accuracy, and reliability of YouTube videos regarding relevant postoperative patient information and postoperative rehabilitation after arthroscopic rotator cuff repair are poor. Videos from medically trained professionals provide significantly higher information quality; however, even these videos lack important information for a better understanding of arthroscopic rotator cuff repair. CLINICAL RELEVANCE: Because of the lack of a peer-review process, available videos on YouTube regarding relevant postoperative patient information and postoperative rehabilitation after arthroscopic rotator cuff repair are of low quality, accuracy, and reliability. However, patients increasingly visit YouTube to gather medical knowledge. Physicians should enlighten patients about these findings and should be able to provide alternative sources of high-quality information.

Pseudotumors in Small-Head Metal-on-Metal Total Hip Arthroplasties at a Minimum Follow-Up of 20 Years.

BACKGROUND: Metal-on-metal (MOM) surfaces in total hip arthroplasty (THA) have been used widely. Serum cobalt and chromium levels have been the standard investigation for follow-up examinations, but magnetic resonance imaging (MRI) with metal artifact reducing sequences has shown good results in detecting pseudotumors. The aim of this study is to survey a significant correlation among MRI findings, serum metal levels, and clinical scores in patients with small-head MOM implants and if serum cobalt and chromium levels are sufficient in detecting patients with pseudotumors in the long-term follow-up. METHODS: At a minimum follow-up of 20 years, 26 patients (29 THAs) of the original 98 patients (105 THAs) included in this study between November 1992 and May 1994 were available for follow-up examination. Clinical scores, serum metal ion levels, and MRIs were obtained. RESULTS: We found mean serum cobalt levels of 1.87 µg/L (±3.44) and chromium levels of 2.23 µg/L (±2.96) and very good clinical and functional results (mean Harris Hip Score 88.6) in the long-term follow-up. Pseudotumors were detected in MRIs of 21 hips. There were no significant differences between patients with or without pseudotumors regarding serum metal levels and the correlation for clinical outcome scores, demographic data, and cup inclination. The cumulative rate of survival was still at 91.4% at 22.8 years. CONCLUSION: This study presents the first published data on small-head MOM hips, comparing metal ion levels, pseudotumors, clinical, and radiological results in a follow-up period of more than 20 years and reveals that serum metal levels are not significantly higher in patients with pseudotumors. LEVEL OF EVIDENCE: Therapeutic Level III.

Inferior performance of established and novel serum inflammatory markers in diagnosing periprosthetic joint infections.

PURPOSE: Besides other diagnostic test methods, established serum inflammatory markers such as serum C-reactive protein or leukocyte count are widely used preoperatively to aid in diagnosing periprosthetic joint infections (PJI). Although low accuracies were reported, these parameters are easily accessible and routinely available. Novel biomarkers with promising results in diagnosing PJI (platelet count to mean platelet volume ratio) or other infectious conditions (percentage of neutrophils, neutrophils to lymphocytes ratio) were described. The purpose of this study was to investigate the diagnostic value of established and novel serum inflammatory biomarkers for the diagnosis of PJI so as to compare the results to find the serum inflammatory marker with the best performance. METHODS: In 177 patients with a previous total hip (n = 91) or knee (n = 86) arthroplasty and indicated revision surgery, the diagnostic value of the routinely available serum inflammatory markers C-reactive protein (CRP), white blood cell count (WBC), percentage of neutrophils (%N), neutrophils to lymphocytes ratio (NLR), fibrinogen and platelet count to mean platelet volume ratio (PC/mPV) were examined retrospectively via receiver operating characteristic curve analysis (AUC). The curves were compared using the z-test. RESULTS: Sensitivities of serum CRP, WBC, %N, NLR, fibrinogen and PC/mPV were calculated with 68%, 36%, 66%, 63%, 69% and 43%, respectively. Specificities were 87%, 89%, 67%, 73%, 89% and 81%, respectively. Serum CRP (0.78) and fibrinogen (0.79) showed significantly better AUCs compared with serum WBC (0.63), %N (0.67), NLR (0.68) and PC/mPV (0.62) (p < 0.0001). Patients with PJI caused by a low-virulent microorganism (median CRP: 17.6 mg/L) obtained lower CRP levels compared with infections caused by high-virulent microorganisms (median CRP: 49.2 mg/L; p = 0.044). The combination of CRP and fibrinogen showed a better sensitivity (77%) with similar specificity (83%) than one method alone but not at a significant level (CRP (p = 0.200); fibrinogen (p = 0.437)). CONCLUSION: Serum CRP and fibrinogen showed the best accuracies among these widely available serum inflammatory parameters. However, due to the insufficient performance, these biomarkers can only be recommended as suggestive criteria in diagnosing PJI. The preoperative workup should always be complemented by more specific tests such as synovial fluid analysis.

High Revision Rates of a Cementless Beta-Titanium Alloy Stem with Contamination-Free Roughened Surface in Primary Total Hip Arthroplasty.

Optimal osseointegration of cementless total hip arthroplasty is essential for high stability and long-term survival. The purpose of this follow-up study was to evaluate the clinical and radiological outcome, the complications, and survival rates of a beta-titanium alloy stem with a specific grit-blasted-free surface. In 192 patients (mean age of 64.4 years), 202 consecutive primary total hip arthroplasties were performed using a cementless Hipstar® stem (Stryker, Duisburg, DE). The Harris Hip Score (HHS) was assessed pre-operatively and post-operatively. Radiolucent lines were evaluated and the implant survival rate was calculated using Kaplan-Meier analysis. The mean follow-up was 7.71 years (range of 5.0-14.0 years). Overall, 15 revisions were performed. Early aseptic stem loosening was observed in six cases (2.97%). Radiolucent-lines adjacent to the stem were detected in 73 cases (83.02%), especially (70.46%) in the Gruen zones 1, 7, 8, and 14. The mean postoperative HHS was 92.65 points (range 42-100). The cumulative survival probability of the stem was 94.4% (95% CI 90.3 to 98.5%). Considering aseptic failure as an endpoint, the cumulative survival rate of the stem was 95.3% (95% CI 0.914 to 0.992) at six years of follow-up. Overall, an inferior mid-term implant survival was observed in comparison to well-established cementless stem designs.

Total Hip Arthroplasty Using Imageless Computer-Assisted Navigation-2-Year Follow-Up of a Prospective Randomized Study.

The purpose of this study is to compare computer-assisted to manual implantation-techniques in total hip arthroplasty (THA) and to find out if the computer-assisted surgery is able to improve the clinical and functional results and reduce the dislocation rate in short-terms after THA. We performed a concise minimum 2-year follow-up of the patient cohort of a prospective randomized study published in 2014 and evaluated if the higher implantation accuracy in the navigated group can be seen as an important determinant of success in total hip arthroplasty. Although a significant difference was found in mean postoperative acetabular component anteversion and in the outliers regarding inclination and anteversion (p < 0.05) between the computer-assisted and the manual-placed group, we could not find significant differences regarding clinical outcome or revision rates at 2-years follow-up. The implantation accuracy in the navigated group can be regarded as an important determinant of success in THA, although no significant differences in clinical outcome could be detected at short-term follow-up. Therefore, further long-term follow-up of our patient group is needed.

[Challenges in Primary Total Hip Arthroplasty]. / Herausforderungen in der primären Hüftendoprothetik.

Total hip arthroplasty (THA) represents a meticulously standardized procedure with highly satisfactory results for surgeons and patients alike. Anyhow, due to rare diseases, anatomic varieties or in posttraumatic situations, the restauration of a normal hip joint anatomy and physiological kinematics can become a big challenge for the treating surgeon. This article gives an overview of the variety of these challenging conditions (including developmental hip dysplasia, osteopetrosis, skeletal dysplasia, Paget's disease and extraarticular deformities) and with a selection of complex cases it should give the reader some thought-provoking impulses considering the management of complex primary THA cases. This includes with the choice of implant, intraoperative characteristics, certain pitfalls and postoperative considerations alike. As a result, it should minimize the risk for complications in these complex cases without minimizing the patient's expectations in a nearly normal hip function and painless movement.

Polyethylene Liner and Femoral Head Exchange in Total Hip Arthroplasty: Factors Associated with Long-Term Success and Failure.

BACKGROUND: Polyethylene (PE) liner and femoral head exchange is commonly used to treat periprosthetic osteolysis associated with PE wear after total hip arthroplasty (THA). The purpose of our study was to determine long-term implant survivorship, risk factors for mechanical failure, clinical outcomes, and complications following PE liner and head exchange. METHODS: We identified 116 hips in 110 patients treated with PE liner and head exchange from 1993 to 2004. There were 64 women (58%) in the series, the mean age at revision surgery was 58 years, and the mean follow-up was 11 years (range, 2 to 23 years). Radiographic review determined the location and size of osteolytic defects before the revision surgery. Implant survivorship was determined using Kaplan-Meier survival analysis. Cox regression analysis was used to determine factors that were predictive of failure. RESULTS: Implant survivorship free of repeat revision for any cause was 91% (95% confidence interval [CI] = 86% to 96%) at 5 years, 81% (95% CI = 74% to 90%) at 10 years, and 69% (95% CI = 55% to 84%) at 15 years. Reasons for repeat revision included aseptic acetabular loosening in 5 hips (4%) and subsequent wear of conventional PE with osteolysis in 5 hips (4%). No patient who underwent revision with highly cross-linked PE subsequently had a repeat revision due to wear. The absolute risk of acetabular component loosening was 23% for patients with osteolysis in 3 zones, 40% for those with osteolysis involving more than half the cup circumference, and 21% for those with osteolytic defects of >600 mm. The mean Harris hip score improved from 77 before the PE liner and head exchange to 87 after it (p < 0.001). The most common complication was dislocation, which occurred in 19 hips (16%). CONCLUSIONS: PE liner and head exchange provides acceptable long-term implant survivorship with good clinical outcomes. Complications are not uncommon, and steps should be taken to mitigate hip instability. Acetabular revision may be considered when in situ components have a poor track record or are malpositioned, or when preoperative radiographs demonstrate large osteolytic defects threatening cup fixation. Use of highly cross-linked PE at revision was protective against subsequent PE wear and osteolysis, although this did not reach significance. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Distal femoral reconstruction following failed total knee arthroplasty is accompanied with risk for complication and reduced joint function.

BACKGROUND: Substantial bone loss following failed total knee arthroplasty (TKA) represents a major challenge in revision arthroplasty, that can require distal femoral reconstruction (DFR). In this study, we aimed to assess the clinical outcome and the complication frequencies of individuals who underwent DFR with modular megaprostheses. Additionally, we aimed to compare functional outcome measures after DFR in these sophisticated cases to an age-matched control group of total knee prostheses to quantify the potential loss of function. METHODS: A retrospective chart review of 30 consecutive patients after DFR from 1997 to 2017 with a mean age of 74.38 years (± 10.1) was performed. Complications were classified according to the Henderson classification. Knee Society Score (KSS) was calculated and range of motion (ROM) was assessed. RESULTS: Thirteen (43.3%) patients had at least one complication requiring revision surgery. Revision-free survival was 74.8% at one year, 62.5% at three and 40.9% at 10 years post-op. Soft-tissue failure complications were found in three (10.0%) patients, aseptic loosening in four (13.3%) patients, structural failure in one (3.3%) patient and infection in eight (26.6%) patients. Of those with infection, five (16.6%) experienced ongoing prosthetic joint infection and three (10.0%) developed new infection after distal femur reconstruction. Patients with DFR achieved 69.3% of KSS pain score, 23.1% KSS function score and 76.2% of ROM compared to patients with primary TKA. CONCLUSIONS: DFR after failed TKA represents a treatment procedure with high risk for complication in this particular group. Despite the prospect of rapid postoperative mobilization, reduced functionality, range of motion and mobilization have to be considered when choosing this treatment option.

A comparative study of intraoperative frozen section and alpha defensin lateral flow test in the diagnosis of periprosthetic joint infection.

Background and purpose - For decision-making (aseptic vs. septic), surgeons rely on intraoperatively available tests when a periprosthetic joint infection (PJI) cannot be confirmed or excluded preoperatively. We compared and evaluated the intraoperative performances of the frozen section and the alpha defensin lateral flow test in the diagnosis of PJI. Patients and methods - In this prospective study, consecutive patients with indicated revision surgery after arthroplasty were included. Patients were classified as having PJI using the MusculoSkeletal Infection criteria. The presence of alpha defensin was determined using the lateral flow test intraoperatively. During revision surgery, tissue samples were harvested for frozen and permanent section. Analysis of diagnostic accuracy was based on receiver-operating characteristics. Results - 101 patients (53 hips, 48 knees) were eligible for inclusion. Postoperatively, 29/101 patients were diagnosed with PJI, of which 8/29 cases were definitely classified as septic preoperatively. Of the remainder 21 septic cases, the intraoperative alpha defensin test and frozen section were positive in 13 and 17 patients, respectively. Sensitivities of the alpha defensin test and frozen section were 69% and 86%, respectively. The area under the curves of both tests showed a statistically significant difference (p = 0.006). Interpretation - The frozen section showed a significantly higher performance compared with the alpha defensin test and a near perfect concordance with the definitive histology, and therefore remains an appropriate intraoperative screening test in diagnosing PJI. Although the sensitivity of the alpha defensin test was lower compared with that of frozen section, this test is highly specific for confirming the diagnosis of PJI.

Dual-energy CT and ceramic or titanium prostheses material reduce CT artifacts and provide superior image quality of total knee arthroplasty.

PURPOSE: To evaluate the influence of different scan parameters for single-energy CT and dual-energy CT, as well as the impact of different material used in a TKA prosthesis on image quality and the extent of metal artifacts. METHODS: Eight pairs of TKA prostheses from different vendors were examined in a phantom set-up. Each pair consisted of a conventional CoCr prosthesis and the corresponding anti-allergic prosthesis (full titanium, ceramic, or ceramic-coated) from the same vendor. Nine different (seven dual-energy CT and two single-energy CT) scan protocols with different characteristics were used to determine the most suitable CT protocol for TKA imaging. Quantitative image analysis included assessment of blooming artifacts (metal implants appear thicker on CT than they are, given as virtual growth in mm in this paper) and streak artifacts (thick dark lines around metal). Qualitative image analysis was used to investigate the bone-prosthesis interface. RESULTS: The full titanium prosthesis and full ceramic knee showed significantly fewer blooming artifacts compared to the standard CoCr prosthesis (mean virtual growth 0.6-2.2 mm compared to 2.9-4.6 mm, p < 0.001). Dual-energy CT protocols showed less blooming (range 3.3-3.8 mm) compared to single-energy protocols (4.6-5.5 mm). The full titanium and full ceramic prostheses showed significantly fewer streak artifacts (mean standard deviation 77-86 Hounsfield unit (HU)) compared to the standard CoCr prosthesis (277-334 HU, p < 0.001). All dual-energy CT protocols had fewer metal streak artifacts (215-296 HU compared to single-energy CT protocols (392-497 HU)). Full titanium and ceramic prostheses were ranked superior with regard to the image quality at the bone/prosthesis interface compared to a standard CoCr prosthesis, and all dual-energy CT protocols were ranked better than single-energy protocols. CONCLUSIONS: Dual-energy CT and ceramic or titanium prostheses reduce CT artifacts and provide superior image quality of total knee arthroplasty at the bone/prosthesis interface. These findings support the use of dual-energy CT as a solid imaging base for clinical decision-making and the use of full-titanium or ceramic prostheses to allow for better CT visualization of the bone-prosthesis interface.

Modern cemented total knee arthroplasty design shows a higher incidence of radiolucent lines compared to its predecessor.

PURPOSE: To prevent early failure it is necessary to evaluate modern TKA system for possible shortcomings during implantation. The aim of this study was to evaluate the radiographic outcome and short-term survival of a modern cemented primary TKA system compared to its predecessor. METHODS: The authors reviewed 529 primary cemented TKAs [276 Attune (ATT) and 253 PFC Sigma (PFC)], which were implanted between 2014 and 2017 concerning the radiographic outcome and short-term survival. Radiographs were taken before discharge, 6 weeks, 6 months and 12 months postoperatively. Radiographic analysis was performed by two independent assessors using the Modern Knee Society Radiographic Evaluation System. RESULTS: The incidence of radiolucent lines was significantly higher in the ATT group compared with the PFC group 12 months postoperatively (35.1%; n = 97 TKAs vs. 7.5%; n = 19 TKAs; p < 0.001). Survival analysis could not show any differences in revision-free survival or revision rate. CONCLUSION: The modern primary TKA system shows an increased number of radiolucent lines, especially on the tibial component in this short-term analysis and may mostly be due to technique-related issues. Patients with those radiolucent lines even though they show no clinical evidence for loosening should be closely monitored at regular intervals. These findings are of vital clinical importance because surgeons should be aware of particular challenges in preparation and cementing technique once they are using this TKA-system. LEVEL OF EVIDENCE: Retrospective cohort study, Level III.

Galectin-8 induces functional disease markers in human osteoarthritis and cooperates with galectins-1 and -3.

The reading of glycan-encoded signals by tissue lectins is considered a major route of the flow of biological information in many (patho)physiological processes. The arising challenge for current research is to proceed from work on a distinct protein to family-wide testing of lectin function. Having previously identified homodimeric galectin-1 and chimera-type galectin-3 as molecular switches in osteoarthritis progression, we here provide proof-of-principle evidence for an intra-network cooperation of galectins with three types of modular architecture. We show that the presence of tandem-repeat-type galectin-8 significantly correlated with cartilage degeneration and that it is secreted by osteoarthritic chondrocytes. Glycan-inhibitable surface binding of galectin-8 to these cells increased gene transcription and the secretion of functional disease markers. The natural variant galectin-8 (F19Y) was less active than the prevalent form. Genome-wide array analysis revealed induction of a pro-degradative/inflammatory gene signature, largely under control of NF-κB signaling. This signature overlapped with respective gene-expression patterns elicited by galectins-1 and -3, but also presented supplementary features. Functional assays with mixtures of galectins that mimic the pathophysiological status unveiled cooperation between the three galectins. Our findings shape the novel concept to consider individual galectins as part of a so far not realized teamwork in osteoarthritis pathogenesis, with relevance beyond this disease.

Vascular Morphogenesis in the Context of Inflammation: Self-Organization in a Fibrin-Based 3D Culture System.

Introduction: New vessel formation requires a continuous and tightly regulated interplay between endothelial cells with cells of the perivascular microenvironment supported by mechanic-physical and chemical cues from the extracellular matrix. Aim: Here we investigated the potential of small fragments of synovial tissue to form de novo vascular structures in the context of inflammation within three dimensional (3D) fibrin-based matrices in vitro, and assessed the contribution of mesenchymal stromal cell (MSC)-immune cell cross-talk to neovascularization considering paracrine signals in a fibrin-based co-culture model. Material and Methods: Synovial tissue fragments from patients with rheumatoid arthritis (RA) and inflammatory osteoarthritis (OA) were cultivated within 3D fibrin matrices for up to 4 weeks. Cellular and structural re-arrangement of the initially acellular matrix were documented by phase contrast microscopy and characterized by confocal laser-scanning microscopy of topographically intact 3D cultures and by immunohistochemistry. MSC-peripheral blood mononuclear cell (PBMC) co-cultures in the 3D fibrin system specifically addressed the influence of perivascular cell interactions to neo-vessel formation in a pro-inflammatory microenvironment. Cytokine levels in the supernatants of cultured explant tissues and co-cultures were evaluated by the Bio-Plex cytokine assay and ELISA. Results: Vascular outgrowth from the embedded tissue into the fibrin matrix was preceded by leukocyte egress from the tissue fragments. Neo-vessels originating from both the embedded sample and from clusters locally formed by emigrated mononuclear cells were consistently associated with CD45+ leukocytes. MSC and PBMC in co-culture formed vasculogenic clusters. Clusters and cells with endothelial phenotype emerging from them, were surrounded by a collagen IV scaffold. No vascular structures were observed in control 3D monocultures of PBMC or MSC. Paracrine signals released by cultured OA tissue fragments corresponded with elevated levels of granulocyte-colony stimulating factor, vascular endothelial growth factor and interleukin-6 secreted by MSC-PBMC co-cultures. Conclusion: Our results show that synovial tissue fragments with immune cell infiltrates have the potential to form new vessels in initially avascular 3D fibrin-based matrices. Cross-talk and cluster formation of MSC with immune cells within the 3D fibrin environment through self-organization and secretion of pro-angiogenic paracrine factors can support neo-vessel growth.

Distinct activity of the bone-targeted gallium compound KP46 against osteosarcoma cells - synergism with autophagy inhibition.

BACKGROUND: Osteosarcoma is the most frequent primary malignant bone tumor. Although survival has distinctly increased due to neoadjuvant chemotherapy in the past, patients with metastatic disease and poor response to chemotherapy still have an adverse prognosis. Hence, development of new therapeutic strategies is still of utmost importance. METHODS: Anticancer activity of KP46 against osteosarcoma cell models was evaluated as single agent and in combination approaches with chemotherapeutics and Bcl-2 inhibitors using MTT assay. Underlying mechanisms were tested by cell cycle, apoptosis and autophagy assays. RESULTS: KP46 exerted exceptional anticancer activity at the nanomolar to low micromolar range, depending on the assay format, against all osteosarcoma cell models with minor but significant differences in IC50 values. KP46 treatment of osteosarcoma cells caused rapid loss of cell adhesion, weak cell cycle accumulation in S-phase and later signs of apoptotic cell death. Furthermore, already at sub-cytotoxic concentrations KP46 reduced the migratory potential of osteosarcoma cells and exerted synergistic effects with cisplatin, a standard osteosarcoma chemotherapeutic. Moreover, the gallium compound induced signs of autophagy in osteosarcoma cells. Accordingly, blockade of autophagy by chloroquine but also by the Bcl-2 inhibitor obatoclax increased the cytotoxic activity of KP46 treatment significantly, suggesting autophagy induction as a protective mechanism against KP46. CONCLUSION: Together, our results identify KP46 as a new promising agent to supplement standard chemotherapy and possible future targeted therapy in osteosarcoma.

Cementless Total Hip Arthroplasty in Octogenarians.

BACKGROUND: Although several studies indicate excellent results for cementless implants, controversy persists regarding its use in elderly patients. We determined to evaluate the outcome on patients aged over 80 years who were treated with cementless total hip arthroplasty for primary osteoarthritis of the hip. METHODS: We assessed the data of 162 consecutive total hip arthroplasties in octogenarian patients (mean age 83 years, range 80-96 years). A control group was created, consisting of 342 patients aged younger than 80 years (mean age 65 years, range 37-79 years). The median follow-up of the cohort was 128.4 months (range 6-211). RESULTS: Competing risk analyses revealed a cumulative implant survival of 98.1% at 5 and 10 years in the study group compared to 99.1% and 98.4% in the control group, taking system exchange as the end point. No differences in regard to system exchange could be detected between the groups. A significantly worsened complication-free survival rate was evident in the octogenarian group. Osteoporosis was the most powerful risk factor that proved to have a significant negative impact on development of complications. CONCLUSION: Uncemented total hip arthroplasty is a viable option for the elderly patient. In this population sector, an excellent rate of implant survival can be expected. However, a significant increase of total complications in the octogenarian group could be detected, and was mainly caused by an elevated number of early postoperative complications. Osteoporosis turned out to be a strong risk factor in regard to complication-free survival. Surgeons should therefore be aware of this.

Midterm Results of a New Rotating Hinge Knee Implant: A 5-Year Follow-Up.

BACKGROUND: In the current study, we investigated midterm results of a new rotating hinge total knee arthroplasty (EnduRo prosthesis), which uses a new bearing material (CFR PEEK). METHODS: We prospectively analysed data of 50 patients with a minimum follow-up of 5 years. In 24 (48%) patients, a primary implantation was performed and 26 (52%) were revision cases. Clinical and radiographic examinations were performed preoperatively as well as postoperatively after 3 and 12 months and annually thereafter. The Knee Society Score (KSS), WOMAC, Oxford Knee Score (OKS), and range of motion (ROM) were used for clinical assessment. RESULTS: KSS, WOMAC, OKS, and ROM significantly improved between the preoperative and the follow-up investigations. The overall survival rate with revision for any reason as an endpoint was 77.9% after five years. The number of complications was significantly higher in the revision group (p = 0.003). CONCLUSION: The EnduRo prosthesis provides highly satisfying clinical and functional results in severe primary as well as in revision cases. Implant-associated complications were rare. However, in cases of revision surgery, the risk for complications was considerably high, mostly related to previous joint infections and poor soft tissue quality.

CD44 drives aggressiveness and chemoresistance of a metastatic human osteosarcoma xenograft model.

BACKGROUND: Osteosarcoma is the most common primary malignant bone tumor with a 5 year survival rate of up to 70%. However, patients with metastatic disease have still a very poor prognosis. Osteosarcoma metastasis models are essential to develop novel treatment strategies for advanced disease. METHODS: Based on a serial transplantation approach, we have established a U-2 OS osteosarcoma xenograft model with increased metastatic potential and compared it to other metastatic osteosarcoma models from international sources. Subclones with differing invasive potential were compared for genomic gains and losses as well as gene expression changes by several bioinformatic approaches. Based on the acquired results, the effects of a shRNA-mediated CD44 mRNA knockdown on migration, invasion and chemosensitivity were evaluated. RESULTS: The CD44 gene was part of an amplified region at chromosome 11p found in both U-2 OS subclones with enhanced metastatic potential but not in parental U-2 OS cells, corresponding with distinct CD44 overexpression. Accordingly, shRNA-mediated CD44 knockdown significantly attenuated osteosarcoma cell migration, invasion, and viability especially in the metastatic subclones of U-2 OS and Saos-2 cells. Metastatic subclones generally were hypersensitive against the integrin inhibitor cilengitide paralleled by alterations in integrin expression pattern following CD44 knock-down. Additionally, attenuation of CD44 expression sensitized these cell models against osteosarcoma chemotherapy with doxorubicin but not methotrexate and cisplatin. CONCLUSIONS: The osteosarcoma xenograft models with increased metastatic potential developed in this study can be useful for identification of mechanisms driving metastasis and resistance towards clinically used and novel therapeutic regimens.

Galectin-3 Induces a Pro-degradative/inflammatory Gene Signature in Human Chondrocytes, Teaming Up with Galectin-1 in Osteoarthritis Pathogenesis.

Inflammatory chemo- and cytokines and matrix-degrading proteases underlie the progression of osteoarthritis (OA). Aiming to define upstream regulators for these disease markers, we pursued initial evidence for an upregulation of members of the adhesion/growth-regulatory galectin family. Immunohistochemical localization of galectin-3 (Gal-3) in sections of human cartilage with increasing levels of degeneration revealed a linear correlation reaching a chondrocyte positivity of 60%. Presence in situ was cytoplasmic, the lectin was secreted from OA chondrocytes in culture and binding of Gal-3 yielded lactose-inhibitable surface staining. Exposure of cells to the lectin led to enhanced gene expression and secretion of functional disease markers. Genome-wide transcriptomic analysis broadened this result to reveal a pro-degradative/inflammatory gene signature under the control of NF-κB. Fittingly, targeting this route of activation by inhibitors impaired the unfavourable response to Gal-3 binding, as also seen by shortening the lectin's collagen-like repeat region. Gal-3's activation profile overlaps with that of homodimeric galectin-1 (Gal-1) and also has distinctive (supplementing) features. Tested at subsaturating concentrations in a mixture, we found cooperation between the two galectins, apparently able to team up to promote OA pathogenesis. In summary, our results suggest that a network of endogenous lectins is relevant for initiating this process cascade.

Recurrence rate and progression of chondrosarcoma is correlated with heat shock protein expression.

Heat shock proteins (HSPs) are involved in tumour immunity, and are correlated with survival and drug resistance in numerous types of cancer. The present study investigated the expression of HSPs and multiple drug resistance (MDR) in human chondrosarcoma. HSP and P-glycoprotein (the MDR1 gene product) expression was evaluated by immunohistochemical analysis of paraffin-embedded sections obtained from 37 patients with chondrosarcoma (19 male and 18 female; aged 33-85 years; mean age, 48.5 years). HSP73 and 90 were significantly overexpressed in patients with local recurrence: HSP73 was expressed in 7/7 patients (100%) with local recurrence and 9/18 patients (50%) without recurrence (P<0.02), while HSP90 was expressed in all patients with recurrence but only 8/18 (44%) without recurrence (P<0.02). A marked association was also identified between HSP expression and survival. HSP72 and 73 were significantly overexpressed in tumours from patients who succumbed to the disease (all positive for HSP72 and 73; P<0.05). No differences were observed between HSP27, 73 or 90-positive or -negative tumours according to age or gender. In addition, HSP72 expression was correlated with differentiation of the tumours (P<0.02). These results indicate that HSP72, 73 and 90 may function as novel prognostic markers for chondrosarcoma, and initiate further studies regarding the use of such markers for the identification of patients with poor prognosis.

EGFR is not a major driver for osteosarcoma cell growth in vitro but contributes to starvation and chemotherapy resistance.

BACKGROUND: Enhanced signalling via the epidermal growth factor receptor (EGFR) is a hallmark of multiple human carcinomas. However, in recent years data have accumulated that EGFR might also be hyperactivated in human sarcomas. Aim of this study was to investigate the influence of EGFR inhibition on cell viability and its interaction with chemotherapy response in osteosarcoma cell lines. METHODS: We have investigated a panel of human osteosarcoma cell lines regarding EGFR expression and downstream signalling. To test its potential applicability as therapeutic target, inhibition of EGFR by gefitinib was combined with osteosarcoma chemotherapeutics and cell viability, migration, and cell death assays were performed. RESULTS: Osteosarcoma cells expressed distinctly differing levels of functional EGFR reaching in some cases high amounts. Functionality of EGFR in osteosarcoma cells was proven by EGF-mediated activation of both MAPK and PI3K/AKT pathway (determined by phosphorylation of ERK1/2, AKT, S6, and GSK3ß). The EGFR-specific inhibitor gefitinib blocked EGF-mediated downstream signal activation. At standard in vitro culture conditions, clinically achievable gefitinib doses demonstrated only limited cytotoxic activity, however, significantly reduced long-term colony formation and cell migration. In contrast, under serum-starvation conditions active gefitinib doses were distinctly reduced while EGF promoted starvation survival. Importantly, gefitinib significantly supported the anti-osteosarcoma activities of doxorubicin and methotrexate regarding cell survival and migratory potential. CONCLUSION: Our data suggest that EGFR is not a major driver for osteosarcoma cell growth but contributes to starvation- and chemotherapy-induced stress survival. Consequently, combination approaches including EGFR inhibitors should be evaluated for treatment of high-grade osteosarcoma patients.