Effect of an Intensified Antibiotic Stewardship Program at an Orthopedic Surgery Department.

Background: Institutional programs such as antibiotic stewardship (ABS) programs offer possibilities to monitor and modify antibiotic usage with the aim of reducing antibiotic resistance. In orthopedic units that treat peri-prosthetic joint infections (PJIs), ABS programs are still rare, however, there is extensive use of high-risk antibiotic agents and an increased risk for the occurrence of Clostridium difficile infections (CDIs). Patients and Methods: An ABS program was implemented at the Department of Orthopedic Surgery at a university hospital. Quarterly antibiotic consumption was measured in defined daily doses (DDDs) per 100 patient-days (PDs) at 10 quarters before the intervention and seven quarters after the intervention. The effect of the new antibiotic policy on drug use rates was evaluated using an interrupted time-series analysis. Estimated changes over time in the incidence of CDIs (cases per 1,000 PDs) were analyzed. Results: A remarkable percentual reduction in second-generation cephalosporin use of 83% (p < 0.001; pre-intervention level, 81.486 DDDs/100 patient-days; post-intervention level, 13.751 DDDs/100 PDs) and clindamycin administration of 78% (p < 0.001; pre-intervention level, 18.982 DDDs/100 PDs; post-intervention level, 4.216 DDDs/100 PDs) was observed after implementation of ABS interventions. Total antibiotic use declined by 25% (p < 0.001; pre-intervention level, 129.078 DDDs/100 PDs; post-intervention level, 96.826 DDDs/100 PDs). Conclusions: This research assessed the positive impact of an intensified ABS program at an orthopedic department specializing in PJIs. Antibiotic stewardship program interventions encourage the reduction of total antibiotic usage and especially high-risk antibiotic agents, associated with the development of antimicrobial resistance.

Peri-Prosthetic Joint Infection of the Knee Causes High Levels of Psychosocial Distress: A Prospective Cohort Study.

Background: Peri-prosthetic joint infection (PJI) is a major complication of knee arthroplasty that can cause long-term disability. In addition to its physical impact, there is a clear psychological burden that has not been measured yet. We hypothesized that the psychosocial burden of PJI can be assessed quantitatively using standardized questionnaires and may be correlated with treatment stage. Methods: Thirty-one patients were enrolled in this longitudinal prospective cohort study from August 2015 to November 2016. Participants had clinically established knee PJI after primary total knee replacement in osteoarthritis according to the Musculoskeletal Infection Society criteria and underwent a standardized two-stage protocol. After explantation of the prosthesis and implantation of a polymethylmethacrylate knee spacer, patients were treated with organism-specific intravenous antibiotics for two weeks, followed by oral antibiotics for four weeks; and then reimplantation was performed in all cases. Psychometrically validated standardized questionnaires were used to measure psychosocial stress via self-assessment at four time points: (1) Before explantation of the prosthesis; (2) after explantation; (3) after the antibiotic treatment before reimplantation; and (4) three months after reimplantation (follow-up). The Patient Health Questionnaire (PHQ)-4, Short Form (SF)-12 (including PSK and KSK), Questions about Life Satisfaction (FLZM) and Fear of Progression (PA-F-KF) (titles and abbreviations in German) scores were interpreted according to cut-off values for depression, fear of progression, anxiety, and quality of life. Results: Eighteen patients (58.1%) showed a PHQ-4 score above the cut-off value for depression at least once, with the highest score before reimplantation (time point 3). On the SF-12, the mean subtest mental scale (PSK) score was 42.6 (± 14.5), and the mean subtest physical scale (KSK) score was 26.9 (± 7.5) over the four time points, which was significantly lower than that of the general German population (PSK 53.1, KSK 44.0; p < 0.05). The SF-12 scores did not change significantly over time. On the FLZ, health was least satisfactory, followed by recreational activities and work. On the PA-F-KF, patients had the greatest fear of being dependent on outside help, drastic medical interventions, and infection progression. The mean PA-F-KF value was 31.24 (± 9.60; values ≥34 are regarded as critical). Conclusion: Peri-prosthetic joint infection is a measurable, relevant psychosocial stressor for patients. Their quality of life and fear of the disease progressing are comparable to those of oncology patients. Routine screening should be conducted to identify affected patients early for appropriate treatment, improving long-term outcomes. Orthopaedic surgeons who treat patients with PJI should initiate by psychologists as well in order to maintain the patient's long-term quality of life.

[Implant-associated joint infections]. / Implantatassoziierte Gelenkinfektionen.

Due to the increasing number of endoprosthetic joint replacement operations in older patients as well as in patients with severe primary diseases and comorbidities, the number of revision operations is continuously increasing due to infections. The infection of an endoprosthesis represents a complex clinical picture. This article provides a detailed overview of the treatment of periprosthetic infections with a focus on the diagnostic approach and treatment decision-making. A differentiation is made in periprosthetic infections between infections with a mature or immature biofilm on the surface of the implant. Depending on this, different treatment concepts are available. Highly acute infections represent an orthopedic/surgical emergency in artificial as well as in native joints. Low-grade infections play a role particularly in the area of exchange endoprosthetics. The greatest possible success is achieved only by the interplay of a timely diagnosis, sufficient surgical approach and individualized anti-infective treatment.

[Native joint infections]. / Native Gelenkinfektionen.

Joint infections are a great challenge for the treating physicians. Infection of a native joint can result in the rapid destruction of the joint if treatment is inadequate or delayed and is associated with severe life-threatening diseases, such as sepsis. This article presents a detailed overview of the treatment of joint infections of native joints with a focus on the diagnostic approach and treatment decisions. Infections in native joints are caused either endogenously by hematogenic spreading or are caused by exogenous factors. A relevant proportion of joint infections in native joints occur in connection with iatrogenic measures, such as operations, synovial punctures and joint infiltrations. Fundamentally, acute infections represent an orthopedic surgical emergency, which is associated with the necessity for immediate operative measures. The best possible success can only be achieved by an interaction between early diagnosis, an adequate surgical approach and a tailor-made anti-infectious treatment. This is also the case with periprosthetic infections, which will be dealt with in detail in a second article.

Prognostic Factors and Outcomes for Patients With Myxofibrosarcoma: A 13-Year Retrospective Evaluation.

BACKGROUND: Soft-tissue sarcomas are rare entities that are divided into approximately 50 histological subtypes. Myxofibrosarcoma (MFS) represents approximately 20% of all soft-tissue sarcomas, especially in elderly patients in their sixth to eighth decades of life. The treatment for soft-tissue sarcomas varies from primary surgical resection to neoadjuvant or adjuvant radiotherapy or cytotoxic chemotherapy. The aim of this study was to evaluate the prognostic factors affecting survival of patients with MFS, taking into account gender, tumour grade, state of the resection margin, local recurrence, use of radiotherapy, presence of metastases and blood levels of haemoglobin and C-reactive protein in a retrospective, single-centre analysis with a minimum follow-up period of 60 months (range=60-156 months). PATIENTS AND METHODS: The study included 34 patients (male/female=20/14). Tumour localization, tumour grade, tumour margins, local recurrence, the use of radiotherapy, the presence of metastasis, and the blood levels of haemoglobin and C-reactive protein preoperatively and during follow-up were evaluated. RESULTS: MFS constituted the most common high-grade sarcoma (G2/G3, 79.4%) in our cohort and was generally located in a lower limb (73.6%). Negative margins (R0) were detected in 67.6% of patients after surgical resection, and local recurrence occurred in 23.5% of all patients after a mean disease-free period of 19.4 months. Both parameters exerted no significant influence on survival. Radiotherapy was performed in a neoadjuvant or an adjuvant setting in 50% of patients (eight neoadjuvant, nine adjuvant). Metastasis occurred after a mean of 20.4 months in 38.2% of the patients. Higher C-reactive protein levels showed a trend towards being associated with worse survival, but the association was not significant (p=0.084); haemoglobin level had no influence on the survival rate (p=0.426). Tumour grade and metastasis were significant prognostic factors of survival (log-rank test p=0.041 and p=0.00007). Ten patients (29.4%) died due to MFS during our follow-up period. CONCLUSION: The tumour grade and metastasis of MFS are independently associated with disease-specific survival, whereas negative surgical margins, local recurrence and blood levels of C-reactive protein and haemoglobin were not significant prognostic factors. The understanding of the molecular biological patterns that result in the metastasis of these tumours will help develop better treatment plans in the future.

Synovial aspiration and serological testing in two-stage revision arthroplasty for prosthetic joint infection: evaluation before reconstruction with a mean follow-up of twenty seven months.

INTRODUCTION: The two-stage revision protocol is the gold standard for controlling and treating low-grade prosthetic joint infections of total hip and total knee arthroplasty. The antibiotic pause for diagnostic reasons before reconstruction (stage two) is discussed in relation to the persistence of the infection and the development of resistant bacterial strains. Serological markers and a synovial analysis are commonly used to exclude the persistence of infection. Therefore, we asked (1) is the serological testing of C-reactive protein and leucocytes a valuable tool to predict a persistence of infection? and (2) what is the role of synovial aspiration of Plymethylmethacrylat (PMMA) spacers in hip and knee joints? MATERIALS AND METHODS: One hundred twelve patients who were MSIS criteria-positive for a prosthetic joint infection were studied, including 45 total hip arthroplasties (THA) and 67 total knee artrhoplasties (TKA) patients. All patients were treated with a two-stage-protocol using a mobile PMMA spacer after a 14-day antibiotic-free interval, during which we measured serological markers (C-reactive protein and leucocytes) and performed synovial aspiration (white blood cell count, polymorphonuclear cell percentage, and microbiological culture) in these patients and compared the results with those of their long-term-follow-up (mean follow-up 27 months, range 24-36 months). RESULTS: Of the 112 patients, 89 patients (79.5%; 95% CI 72-86.9) exhibited infection control after a two-stage exchange, and we detected most methicillin-resistant, coagulase-negative Staphylococci (CoNS) in cases of a persistent infection. The mean sensitivity of serum C-reactive protein in the patients was 0.43 (range 0.23-0.64), and the mean specificity was 0.73 (range 0.64-0.82). For serum leucocytes, the mean sensitivity was 0.09 (range 0-0.29), and the mean specificity was 0.81 (range 0.7-0.92). The mean sensitivity for the WBC count in the synovial fluid (PMMA spacer aspiration) was 0.1 (range 0-0.29), and the mean specificity was 0.79 (range 0.68-0.92). For the PMN percentage, the mean sensitivity was 0.1 (range 0-0.29), and the mean specificity was 0.79 (range 0.68-0.92). No cut-off values could be established for C-reactive protein, leucocytes, WBC count and PMN percentage due to the low AUC. CONCLUSION: No reliable markers were identified for the long-term persistence of infection. C-reactive protein and leucocytes were often elevated, even when the infection was controlled. In addition, normalized serum markers did not exclude the persistence of infection during follow-up. The synovial analysis of the WBC count and PMN percentage did not predict the persistence of infection. However, microbiological synovial fluid analysis is often misleading due to false positive microbiological cultures, which results in overtreatment.

Prospective Analysis of a Sterile, Semi-automated Tissue Biopsy Homogenization Method in the Diagnosis of Prosthetic Joint Infections.

BACKGROUND/AIM: Prosthetic joint infection (PJI) remains a serious complication of total joint arthroplasty. To effectively treat PJI, it is essential to identify the microorganism causing it and be able to combine correct surgical and anti-infective treatments. This cannot always be achieved with the currently employed diagnostic methods. The aim of this study was to evaluate a semi-automated tissue biopsy bead milling method (Ultra-TurrAX, Axonlab AG; Reichenbach, Germany) based on the hypothesis that the results are more sensitive for microbe detection and less prone to contamination. MATERIALS AND METHODS: We included 35 consecutive patients undergoing 38 hip or knee arthroplasty revisions in this study. In addition to manually processed biopsies, we processed tissue specimens harvested intraoperatively using a semi-automated method. The sensitivity and specificity of both methods were calculated using MSIS criteria and sonication results as gold standards. RESULTS: For total hip arthroplasty samples were evaluated separately based on MSIS criteria as the reference standard, Ultra-TurrAX processing yielded 81% (62-100%) sensitivity and 100% specificity. Using sonication as the gold standard, a sensitivity of 80% (60-100%) and specificity of 80% (45-100%) were calculated. In total knee arthroplasty, Ultra-TurrAX processing yielded 27% (1-54%) sensitivity and 57% (20-94%) specificity when using MSIS criteria as the gold standard. Using sonication as the gold standard, a sensitivity of 60% (17-100%) and specificity of 77% (54-100%) were calculated. CONCLUSION: This is the first study to analyze bead mill processing in total hip and knee arthroplasty revisions in a consecutive patient series. The method's sensitivity was comparable to and its specificity superior to regular sample processing results reported in the literature with respect to hip arthroplasties and to both hip and knee arthroplasties collectively. With respect to total knee arthroplasties, the method fared worse in our collective, most likely due to the small number of patients in the sample. Integrating the method into the clinical workflow allowed for speedier and more efficient sample handling and processing. The theoretical advantage of a lower risk of contamination because of fewer manual processing steps is, in our opinion, valid.

Prognostic factors and outcome of Liposarcoma patients: a retrospective evaluation over 15 years.

BACKGROUND: Soft tissue sarcomas are rare entities with over 50 histological subtypes. Liposarcoma (LS) is the most common neoplasm in this group; it is a complex neoplasm that is divided into different histological subtypes. Different therapy options, such as surgical resection, radiation, and chemotherapy, are available. Depending on the subtype, location, status of the resection margins and metastatic status, different therapy options are used. Therefore, the aim of this study was to determine the prognostic factors influencing the survival of patients affected by LS with consideration for the grading, histological subtype, state of the resection margin, size, location, metastases and local recurrence in a retrospective, single-centre analysis over 15 years. METHODS: We included 133 patients (male/female = 67/66) in this study. We recorded the histologic subtype, grade, TNM classification, localization, biopsy technique, tumour margins, number of operations, complications, radiation and dose, chemotherapy, survival, recrudescence, metastases and follow-up. Survivorship analysis was performed. RESULTS: We detected 56 (43%; 95%-CI 34.6-51.6%) atypical LS cases, 21 (16.2%; 95%-CI 9.8-22.5) dedifferentiated LS cases, 40 (30.8%; 95%-CI 22.8-38.7) myxoid LS cases and 12 (9.2%; 95%-CI 4.3-14.2) pleomorphic LS cases. G1 was the most common grade, which was followed by G3. Negative margins (R0) were detected in 67 cases (53.6%; 95%-CI 44.9-62.3) after surgical resection. Local recurrence was detected in 23.6% of cases. The presence of metastases and dedifferentiated LS subtype as well as negative margins, grade and tumour size are significant prognostic factors of the survival rates (p < 0.015). CONCLUSION: Grading, LS subtype, negative margins after surgery, metastases and tumour size are independently associated with disease-specific survival, and patients with local recurrence had lower survival rates. We hope our investigation may facilitate a further prospective study and clinical decision-making in LS.

Increased Resistance of Skin Flora to Antimicrobial Prophylaxis in Patients Undergoing Hip Revision Arthroplasty.

BACKGROUND/AIM: Prosthetic joint infection (PJI) remains a major complication after total joint replacement and is the primary indication for revision arthroplasty. Specifically, coagulase-negative Staphylococci (CNS) can cause low-grade infections. Despite the use of cephalosporin-based antimicrobial prophylaxis (AMP) and antiseptic treatment at the surgical site, evidence suggests that a significant number of cases of dermal CNS results in low-grade PJI. Thus, this study examined the bacterial colonization and resistance patterns at the surgical site. We hypothesized that the bacteria developed resistance to antibiotics that are frequently used in primary and revision total hip arthroplasty (THA) procedures. PATIENTS AND METHODS: Ninety patients, including 63 primary and 27 revision THA patients, were enrolled in this study. For each patient, a single swab of the skin at the surgical site was subjected to clinical microbiology to assess bacterial colonization. Furthermore, resistance to a sentinel panel of antibiotics (benzylpenicillin, erythromycin, tetracycline, oxacillin, fusidic acid, clindamycin, gentamicin, levofloxacin/moxifloxacin, rifampicin, linezolid and vancomycin) was tested. RESULTS: In 96.7% of the patients, at least one bacterial strain was identified at the surgical site, with CNS strains comprising 93.1% of the total. The sentinel panel showed that 30.7% of the CNS strains exhibited maximal resistance to oxacillin, a commonly used cephalosporin. Additionally, oxacillin resistance increased 1.9-fold (p=0.042) between primary and revision THA. Notably, 8.1% of the CNS stains found on patients undergoing primary THA were resistant to gentamicin, an aminoglycoside, and this rate increased 4.7-fold (p=0.001) for patients undergoing revision THA. CONCLUSION: CNS strains have significant resistance to standard AMP, particularly in individuals undergoing revision THA.

Distal femoral replacement with the MML system: a single center experience with an average follow-up of 86 months.

BACKGROUND: The aim of this study was to compare the functional outcomes and complication rates after distal femoral replacement (DFR) performed with the modular Munich-Luebeck (MML) modular prosthesis (ESKA/Orthodynamics, Luebeck, Germany) in patients being treated for malignant disease or failed total knee arthroplasty. METHODS: A retrospective review of patient charts and a functional investigation (involving Musculoskeletal Tumor Society Score [MSTS], American Knee Society Score [AKSS], Oxford Knee Score [OKS], Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC], Toronto Extremity Salvage Score [TESS], the 12-Item Short-Form [SF-12] Health Survey, and a failure classification system developed by Henderson et al.) of DFR cases from 2002 to 2015 were conducted. The indications for DFR were malignant tumor resection in the femur (n = 20, group A) or failure of revision total knee arthroplasty without a history of malignant disease (n = 16, group B). RESULTS: One-hundred and twenty-nine patients were treated during the study period. Of these, 82 were analyzed for complications and implant-survival. Further, 36 patients were available for functional assessment after a mean follow-up of 86 months (range: 24-154). There were 75 complications in total. The overall failure rate for DFR was 64.6% (53/82 patients). The most common failure mechanisms were type III (mechanical failure), followed by type I (soft tissue) and type II (aseptic loosening). The mean MSTS score (out of 30) was 17 for group A and 12 for group B. All the clinical outcome scores revealed an age-dependent deterioration of function. CONCLUSION: DFR is an established procedure to restore distal femoral integrity. However, complication rates are high. Post-procedure functionality depends mainly on the patient's age at initial reconstruction.

IT-based Psychosocial Distress Screening in Patients with Sarcoma and Parental Caregivers via Disease-specific Online Social Media Communities.

BACKGROUND: Psychosocial distress can be frequently observed in patients with sarcoma, depicting a relevant clinical problem. However, prospective data collection on psychosocial distress in patients with rare tumors is often time-consuming. In this context, social media such as Facebook can serve as a potential platform to expand research. The aim of this study was to assess the feasibility of psychosocial distress screening in patients with osteosarcoma and Ewing's sarcoma via social media. MATERIALS AND METHODS: For this study an online questionnaire including general information and self-assessment distress measurement tools for patients and parents was created. The link to the questionnaire was then posted on the main page of the two largest disease-specific Facebook communities on osteosarcoma and Ewing's sarcoma. RESULTS: Within 2 months, 28 patients and 58 parents of patients were enrolled. All patients with osteosarcoma and Ewing's sarcoma, as well as the majority of parental caregivers of such patients, showed relevant psychosocial distress levels. CONCLUSION: Crowdsourcing via disease-specific patient communities on Facebook is feasible and provides great potential for acquisition of medical data of rare diseases.

Prosthetic joint infection development of an evidence-based diagnostic algorithm.

BACKGROUND: Increasing rates of prosthetic joint infection (PJI) have presented challenges for general practitioners, orthopedic surgeons and the health care system in the recent years. The diagnosis of PJI is complex; multiple diagnostic tools are used in the attempt to correctly diagnose PJI. Evidence-based algorithms can help to identify PJI using standardized diagnostic steps. METHODS: We reviewed relevant publications between 1990 and 2015 using a systematic literature search in MEDLINE and PUBMED. The selected search results were then classified into levels of evidence. The keywords were prosthetic joint infection, biofilm, diagnosis, sonication, antibiotic treatment, implant-associated infection, Staph. aureus, rifampicin, implant retention, pcr, maldi-tof, serology, synovial fluid, c-reactive protein level, total hip arthroplasty (THA), total knee arthroplasty (TKA) and combinations of these terms. RESULTS: From an initial 768 publications, 156 publications were stringently reviewed. Publications with class I-III recommendations (EAST) were considered. We developed an algorithm for the diagnostic approach to display the complex diagnosis of PJI in a clear and logically structured process according to ISO 5807. CONCLUSIONS: The evidence-based standardized algorithm combines modern clinical requirements and evidence-based treatment principles. The algorithm provides a detailed transparent standard operating procedure (SOP) for diagnosing PJI. Thus, consistently high, examiner-independent process quality is assured to meet the demands of modern quality management in PJI diagnosis.

Diagnostic accuracy of arthroscopic biopsy in periprosthetic infections of the hip.

BACKGROUND: Diagnosis of a low-grade periprosthetic joint infection (PJI) prior to revision surgery can be challenging, despite paramount importance for further treatment. Arthroscopic biopsy of synovial and periprosthetic tissue with subsequent microbiological and histological examination can be beneficial but its specific diagnostic value has not been clearly defined. METHODS: 20 consecutive patients who underwent percutaneous synovial fluid aspiration as well as arthroscopic biopsy due to suspected PJI of the hip and subsequent one- or two-stage revision surgery at our institution between January 2012 and May 2015 were enrolled. Indication was based on the criteria (1) history of PJI and increased levels of erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP), (2) suspicious cell count and differential but negative bacterial culture in synovial aspirate, (3) early loosening (

Implementation of an Algorithm for Prosthetic Joint Infection: Deviations and Problems.

BACKGROUND: The outcome of revision surgery in arthroplasty is based on a precise diagnosis. In addition, the treatment varies based on whether the prosthetic failure is caused by aseptic or septic loosening. Algorithms can help to identify periprosthetic joint infections (PJI) and standardize diagnostic steps, however, algorithms tend to oversimplify the treatment of complex cases. We conducted a process analysis during the implementation of a PJI algorithm to determine problems and deviations associated with the implementation of this algorithm. PATIENTS AND METHODS: Fifty patients who were treated after implementing a standardized algorithm were monitored retrospectively. Their treatment plans and diagnostic cascades were analyzed for deviations from the implemented algorithm. Each diagnostic procedure was recorded, compared with the algorithm, and evaluated statistically. RESULTS: We detected 52 deviations while treating 50 patients. In 25 cases, no discrepancy was observed. Synovial fluid aspiration was not performed in 31.8% of patients (95% confidence interval [CI], 18.1%-45.6%), while white blood cell counts (WBCs) and neutrophil differentiation were assessed in 54.5% of patients (95% CI, 39.8%-69.3%). We also observed that the prolonged incubation of cultures was not requested in 13.6% of patients (95% CI, 3.5%-23.8%). In seven of 13 cases (63.6%; 95% CI, 35.2%-92.1%), arthroscopic biopsy was performed; 6 arthroscopies were performed in discordance with the algorithm (12%; 95% CI, 3%-21%). CONCLUSION: Self-critical analysis of diagnostic processes and monitoring of deviations using algorithms are important and could increase the quality of treatment by revealing recurring faults.

Glucosamine sulfate suppresses the expression of matrix metalloproteinase-3 in osteosarcoma cells in vitro.

BACKGROUND: Glucosamine, a common dietary supplement, has a possible anti-sarcoma effect. However, an understanding of the underlying mechanism of such an effect is limited. For this study we hypothesized that glucosamine suppresses the basal level of matrix metalloproteinase expression in human osteosarcoma cell lines. METHODS: We examined the osteosarcoma cell lines, MG-63 and SaOS-2. Cells were exposed to 0, 10, 50 and 100 µg/ml glucosamine sulfate for 48 h and treatment toxicity was determined through measurement of cell viability and proliferation. Relative gene expression of matrix metalloproteinase (MMP)-2, -3 and -9 was quantified by real-time polymerase chain reaction. Protein levels of MMP-2 and -9 were assessed by ELISA. RESULTS: Administration of 10, 50 or 100 µg/ml glucosamine sulfate had no effect on the cell viability of MG-63 and SaOS-2 cells. A significant reduction of MMP expression in both cell lines was observed only for MMP-3, while a decrease in MMP-9 was seen in SaOS-2 cells. The expression of MMP-2 was not significantly affected in either cell line. Protein level of MMP-3 was reduced in both cell lines upon stimulation with 10 µg/ml glucosamine sulfate whereas for MMP-9 a decrease could only be observed in SaOS-2 cells. CONCLUSION: In this study, we found a pronounced suppressive effect of glucosamine sulfate particularly on MMP-3 and also MMP-9 mRNA and protein levels in osteosarcoma cell lines in vitro. The data warrants further investigations into the potential anti-tumor efficacy of glucosamine sulfate in osteosarcoma.

Hyaluronic Acid Suppresses the Expression of Metalloproteinases in Osteoarthritic Cartilage Stimulated Simultaneously by Interleukin 1ß and Mechanical Load.

PURPOSE: In patients with osteoarthritis (OA), intraarticular injection of hyaluronic acid (HA) frequently results in reduced pain and improved function for prolonged periods of time, i.e. more than 6 months. However, the mechanisms underlying these effects are not fully understood. Our underlying hypothesis is that HA modifies the enzymatic breakdown of joint tissues. METHODS: To test this hypothesis, we examined osteochondral cylinders from 12 OA patients. In a bioreactor, these samples were stimulated by interleukin 1ß (Il1ß) (2 ng/ml) plus mechanical load (2.0 Mpa at 0.5 Hz horizontal and 0.1 Hz vertical rotation), thus the experimental setup recapitulated both catabolic and anabolic clues of the OA joint. RESULTS: Upon addition of HA at either 1 or 3 mg/ml, we observed a significant suppression of expression of metalloproteinase (MMP)-13. A more detailed analysis based on the Kellgren and Lawrence (K&L) OA grade, showed a much greater degree of suppression of MMP-13 expression in grade IV as compared to grade II OA. In contrast to the observed MMP-13 suppression, treatment with HA resulted in a suppression of MMP-1 expression only at 1 mg/ml HA, while MMP-2 expression was not significantly affected by either HA concentration. CONCLUSION: Together, these data suggest that under concurrent catabolic and anabolic stimulation, HA exhibits a pronounced suppressive effect on MMP-13. In the long-run these findings may benefit the development of treatment strategies aimed at blocking tissue degradation in OA patients.

Inter- and intra-observer variability in biopsy of bone and soft tissue sarcomas.

BACKGROUND/AIM: The aim of this study was to analyze the inter- and intra-observer variability regarding biopsy technique in bone and soft tissue sarcoma based on magnetic resonance imaging (MRI). PATIENTS AND METHODS: Thirty-seven MRI scans of bone and soft tissue sarcomas treated in our clinic were randomly selected. Six observers with three different expertise levels were assigned to analyze the scans for suspected entity and preferred biopsy technique at 2 time points with a delay of 8 weeks. RESULTS: The differentiation between bone and soft tissue sarcomas in MRI seemed closely related to the observer's level of experience. Regarding biopsy technique, no inter-observer accordance could be identified in either group. CONCLUSION: We observed an association of inter- and intra-observer agreement regarding suspected tumor entity and the observer's level of experience. The decision for either biopsy technique showed a low inter-observer but high intra-observer variability. These findings suggest that the decision for incisional or core needle biopsy is, even in the expert group, frequently based on personal predilection.