Serum inflammatory parameters are widely used to aid in diagnosing a periprosthetic joint infection (PJI). Due to their limited performances in the literature, novel and more accurate biomarkers are needed. Serum albumin-to-globulin ratio (AGR) and serum CRP-to-albumin ratio (CAR) have previously been proposed as potential new parameters, but results were mixed. The aim of this study was to assess the diagnostic accuracy of AGR and CAR in diagnosing PJI and to compare them to the established and widely used marker CRP. From 2015 to 2022, a consecutive series of 275 cases of revision total hip (n = 129) and knee arthroplasty (n = 146) were included in this retrospective cohort study. Based on the 2021 European Bone and Joint Infection Society (EBJIS) definition, 144 arthroplasties were classified as septic. Using receiver operating characteristic curve (ROC) analysis, the ideal thresholds and diagnostic performances were calculated. The areas under the curve (AUCs) were compared using the z-test.Aims
Methods
Intervertebral disc (IVD) degeneration is responsible for severe clinical symptoms including chronic back pain. Galectins are a family of carbohydrate-binding proteins, some of which can induce functional disease markers in IVD cells and other musculoskeletal diseases. Galectins −4 and −8 were shown to trigger disease-promoting activity in chondrocytes but their effects on IVD cells have not been investigated yet. This study elucidates the role of galectin-4 and −8 in IVD degeneration. Immunohistochemical evidence for the presence of galectin-4 and −8 in the IVD was comparatively provided in specimens of 36 patients with spondylochondrosis, spondylolisthesis, or spinal deformity. Confocal microscopy revealed co-localization of galectin-4 and −8 in chondrocyte clusters of degenerated cartilage. The immunohistochemical presence of galectin-4 correlated with histopathological and clinical degeneration scores of patients, whereas galectin-8 did not show significant correlations. The specimens were separated into annulus fibrosus (AF), nucleus pulposus (NP) and endplate, which was confirmed histologically. Separate cell cultures of AF and NP (n=20) were established and characterized using cell type-specific markers. Potential binding sites for galectins including sialylated N-glycans and LacdiNAc structures were determined in AF and NP cells using LC/ESI-MS-MS. To assess galectin functions, cell cultures were treated with recombinant galectin-4 or −8, in comparison to IL-1β, and analyzed using RT-qPCR and In-cell Western blot. In vitro, both galectins triggered the induction of functional disease markers (CXCL8 and MMP3) on mRNA level and activated the nuclear factor-kB pathway. NP cells were significantly more responsive to galectin-8 and Il-1β than AF cells. Phosphorylation of p-65 was time-dependently induced by both galectins in both cell types to a comparable extent. Taken together, this study provides evidence for a functional role of glycobiological processes in IVD degeneration and highlights galectin-4 and −8 as regulators of pro-inflammatory and degrative processes in AF and NP cells.
Serum parameters continue to be a focus of research in diagnosing periprosthetic joint infections (PJI). Several workgroups have recently proposed serum Albumin-Globulin-Ratio (AGR) as a potential new biomarker. Due to controversies in the literature, its usability in clinical practice remains uncertain. The aim of this study was to assess the value of serum AGR in diagnosing PJI preoperatively, especially in comparison with the well-established marker C-reactive Protein (CRP). From January 2015 to June 2022, patients with indicated revision hip (rTHA) and knee (rTKA) arthroplasty were included in this retrospective cohort study of prospectively collected data. A standardized diagnostic workup was performed using the 2021 European Bone and Joint Infection Society (EBJIS) definition of PJI, excluding CRP. Diagnostic accuracies of serum AGR and CRP were calculated by receiver operating characteristic curve (ROC) analysis. A z-test was used to compare the area under the curves (AUC).Aim
Method
Odontoid fracture of the second cervical vertebra (C2) is the most common spinal fracture type in elderly patients. However, very little is known about the biomechanical fracture mechanisms, but could play a role in fracture prevention and treatment. This study aimed to investigate the biomechanical competence and fracture characteristics of the odontoid process. A total of 42 human C2 specimens (14 female and 28 male, 71.5 ± 6.5 years) were scanned via quantitative computed tomography, divided in 6 groups (n = 7) and subjected to combined quasi-static loading at a rate of 0.1 mm/s until fracturing at inclinations of −15°, 0° and 15° in sagittal plane, and −50° and 0° in transverse plane. Bone mineral density (BMD), specimen height, fusion state of the ossification centers, stiffness, yield load, ultimate load, and fracture type according to Anderson and d'Alonzo were assessed. While the lowest values for stiffness, yield, and ultimate load were observed at load inclination of 15° in sagittal plane, no statistically significant differences could be observed among the six groups (p = 0.235, p = 0.646, and p = 0.505, respectively). Evaluating specimens with only clearly distinguishable fusion of the ossification centers (n = 26) reveled even less differences among the groups for all mechanical parameters. BMD was positively correlated with yield load (R² = 0.350, p < 0.001), and ultimate load (R² = 0.955, p < 0.001), but not with stiffness (p = 0.070). Type III was the most common fracture type (23.5%). These biomechanical outcomes indicate that load direction plays a subordinate role in traumatic fractures of the odontoid process in contrast to BMD which is a strong determinant of stiffness and strength. Thus, odontoid fractures appear to result from an interaction between load magnitude and bone quality.
Screw fixation is an established method for anterior cruciate ligament (ACL) reconstruction, although with a high rate of implant-related complications. An allograft system for implant fixation in ACL reconstruction, the Shark Screw ACL (surgebright GmbH) could overcome some of the shortcomings of bioabsorbable screws, such as foreign body reaction, need for implant removal and imaging artefacts. However, it needs to provide sufficient mechanical stability. Therefore, the aim of this study was to investigate the biomechanical stability, especially graft slippage, of the novel allograft system versus a conventional bioabsorbable interference screw (BioComposite Interference Screw; Arthrex Inc.) for tibial implant fixation in ACL reconstruction. Twenty-four paired human proximal tibiae (3 female, 9 male, 72.7 ± 5.6 years) underwent ACL reconstruction. The quadrupled semitendinosus and gracilis tendon graft were fixed in one specimen of each pair using the allograft fixation system Shak Screw ACL and the contralateral one using an interference screw. All specimens were cyclically loaded at 1 Hz with peak load levels monotonically increased from 50 N at a rate of 0.1 N/cycle until catastrophic failure. Relative movements of the graft versus the tibia were captured with a stereographic optical motion tracking system (Aramis SRX; GOM GmbH). The two fixation methods did not demonstrate any statistical difference in ultimate load at graft slippage (p = 0.24) or estimated survival at slippage (p = 0.06). Both, the ultimate load and estimated survival until failure were higher in the interference screw (p = 0.04, and p = 0.018, respectively). Graft displacement at ultimate load reached values of up to 7.2 mm (interference screw) and 11.3 mm (Shark Screw ACL). The allograft screw for implant fixation in ACL reconstruction showed similar behavior in terms of graft slippage compared to the conventional metal interference screw but underperformed in terms of ultimate load. However, the ultimate load may not be considered a direct indicator of clinical failure.
Ten to twenty percent of patients are dissatisfied with the clinical result after total knee arthroplasty (TKA). Aim of this study was to investigate the impact of personality traits on patient satisfaction and subjective outcome of TKA. We investigated 80 patients with 86 computer navigated TKAs (Emotion 84% of our patients were satisfied, while 16% were not satisfied with clinical outcome. The FPI-R showed statistically significant influence of four personality traits on patient satisfaction: life satisfaction ( The results of our study show that personality traits may influence patient satisfaction and clinical outcome after TKA. Thus, patients personality traits may be a useful predictive factor for postoperative satisfaction after TKA.
Diagnosing periprosthetic joint infections (PJI) can be very challenging, especially infections caused by low virulence microorganisms. No single test with a 100% accuracy is available yet. Hence, different infection definitions were introduced to improve the diagnostic confidence and quality of research articles. Due to constant developments in this field, infection definitions are adopted continuously. The aim of our study was to find the most sensitive currently available infection definition among three currently used criteria (International Consensus Meeting – criteria 2018 (ICM), Infectious Diseases Society of America - criteria 2013 (IDSA), and European Bone and Joint Infection Society – criteria 2021 (EBJIS)) for the diagnosis of PJI. Between 2015 and 2020, patients with an indicated revision surgery due to septic or aseptic failure after a total hip or knee replacement were included in this retrospective analysis of prospectively collected data. A standardized diagnostic workup was done in all patients. The components of the IDSA-, ICM-, and EBJIS- criteria for the diagnosis of PJI were identified in each patient.Aim
Method
This study evaluated the definitions developed by the European Bone and Joint Infection Society (EBJIS) 2021, the International Consensus Meeting (ICM) 2018, and the Infectious Diseases Society of America (IDSA) 2013, for the diagnosis of periprosthetic joint infection (PJI). In this single-centre, retrospective analysis of prospectively collected data, patients with an indicated revision surgery after a total hip or knee arthroplasty were included between 2015 and 2020. A standardized diagnostic workup was performed, identifying the components of the EBJIS, ICM, and IDSA criteria in each patient.Aims
Methods
To develop an early implant instability murine model and explore the use of intermittent parathyroid hormone (iPTH) treatment for initially unstable implants. 3D-printed titanium implants were inserted into an oversized drill-hole in the tibiae of C57Bl/6 mice (n = 54). After implantation, the mice were randomly divided into three treatment groups (phosphate buffered saline (PBS)-control, iPTH, and delayed iPTH). Radiological analysis, micro-CT (µCT), and biomechanical pull-out testing were performed to assess implant loosening, bone formation, and osseointegration. Peri-implant tissue formation and cellular composition were evaluated by histology.Aims
Methods
Although established serum inflammatory biomarkers, such as serum C-reactive protein (CRP) and serum white blood cell count (WBC), showed low accuracies in the literature, they are still commonly used in diagnosing periprosthetic joint infections (PJI). For a sufficient preoperative diagnosis novel more accurate serum parameters are needed. The aim of our study was to evaluate the performances of the established and novel routinely available serum parameters in diagnosing periprosthetic joint infections when using the proposed European Bone and Joint Infection Society (pEBJIS) criteria. In this retrospective study, 177 patients with an indicated revision surgery after a total joint replacement were included from 2015 to 2019. The easily accessible and routinely available serum parameters CRP, WBC, the percentage of neutrophils (%N), the neutrophils to lymphocytes ratio (NLR), fibrinogen and the platelet count to mean platelet volume ratio (PC/mPV) were evaluated preoperatively. The performances were examined via receiver operating characteristic (ROC) curve analysis (AUC). The curves were compared using the z-test. Seventy-five cases (42%) showed a PJI based on the pEBJIS-criteria.Aim
Method
Histology is an established tool in diagnosing periprosthetic joint infections (PJIs). Different thresholds, using various infection definitions and histopathological criteria, have been described. This study determined the performance of different thresholds of polymorphonuclear neutrophils (≥ 5 PMN/HPF, ≥ 10 PMN/HPF, ≥ 23 PMN/10 HPF) , when using the European Bone and Joint Infection Society (EBJIS), Infectious Diseases Society of America (IDSA), and the International Consensus Meeting (ICM) 2018 criteria for PJI. A total of 119 patients undergoing revision total hip (rTHA) or knee arthroplasty (rTKA) were included. Permanent histology sections of periprosthetic tissue were evaluated under high power (400× magnification) and neutrophils were counted per HPF. The mean neutrophil count in ten HPFs was calculated (PMN/HPF). Based on receiver operating characteristic (ROC) curve analysis and the z-test, thresholds were compared.Aims
Methods
Initial post-operative implant instability leads to impaired osseointegration, one of the most common reasons for aseptic loosening and revision surgery. In this study, we developed a novel murine model of implant instability and demonstrated the anabolic effect of immediate and delayed intermittent Parathyroid Hormone (iPTH) treatment in the setting of instability-induced osseointegration failure. 3D-printed titanium implants were inserted in an oversized drill-hole in the tibia of C57Bl/6 mice (n=54). After implantation, the mice were randomly divided in 3 treatment groups (control: PBS-vehicle; iPTH; delayed iPTH). Radiographic analysis was performed to confirm signs of implant loosening. Peri-implant tissue formation was assessed through histology. Osseointegration was assessed through µCT and biomechanical pullout testing.Introduction
Methods
Second-generation metal-on-metal (MoM) articulations in total hip arthroplasty (THA) were introduced in order to reduce wear-related complications. The current study reports on the serum cobalt levels and the clinical outcome at a minimum of 20 years following THA with a MoM (Metasul) or a ceramic-on-polyethylene (CoP) bearing. The present study provides an update of a previously published prospective randomized controlled study, evaluating the serum cobalt levels of a consecutive cohort of 100 patients following THA with a MoM or a CoP articulation. A total of 31 patients were available for clinical and radiological follow-up examination. After exclusion of 11 patients because of other cobalt-containing implants, 20 patients (MoM (n = 11); CoP (n = 9)) with a mean age of 69 years (42 to 97) were analyzed. Serum cobalt levels were compared to serum cobalt levels five years out of surgery.Aims
Methods
Periprosthetic joint infections are a devastating complication after modular endoprosthetic reconstruction following resection of a musculoskeletal tumour. Due to long operating times, soft tissue dissection and immunosuppression, the infection rate after limb salvage is high and ranges between 8% and 15%. The aim of this retrospective single centre study was to assess the reinfection and re-reinfection rate after septic complications of megaprostheses. In this retrospective study, 627 patients with a primary replacement of a musculoskeletal tumour of the lower limb and reconstruction by a megaprosthesis were recorded from 1983 – 2016. 83 out of 621 patients available for follow-up experienced an infection (13.4%). Two patients were treated with debridement and removal of the mobile parts, 61 patients with a one-stage revision, 16 patients with a two-stage revision, and 4 patients with an amputation. The mean follow up was 133 months (range: 2 – 423 months).Aim
Method
Aim of the study was to find out whether patients with positive minor criteria but without meeting the MSIS definition have a difference in the outcome after revision-surgery compared to patients without any MSIS-criteria? And does the reason for revision-surgery (eg. loosening) have an additional influence on the outcome parameters in patients with positive minor criteria? A retrospective matched-pair analysis with 98 patients who had undergone revision-surgery after TJA was performed. Forty-nine patients who showed 1 to 3 positive minor criteria (PMC) whereas 49 patients without any positive minor criteria (aseptic complications control group) were compared regarding re-revision-rate and revision-free survival. Patients were matched regarding sex, age, joint and comorbidities using the classification system by McPherson et al. Reasons for revisions were categorized in loosening, body wear, periprosthetic fracture/mechanical failure and soft-tissue complication. Endpoints were defined as re-revision for any cases.Aim
Method
Quantitative assessment of alpha-Defensin offers a promising approach for diagnosing a periprosthetic joint infection (PJI) with sensitivities and specificities ranging from 97% to 100% and 95% to 100%, respectively. However, to the best of our knowledge and after due inquiry little information exists concerning qualitative measurements of alpha-Defensin. The aim of this study was to assess the diagnostic accuracy of the alpha-Defensin test, a lateral flow test for the qualitative detection of alpha-Defensin. In this study, 50 patient with indicated revision surgery met the inclusion criteria due to septic or aseptic loosening. In addition to clinical standard diagnostics of PJI, the alpha-Defensin testAim
Method
The total hip arthroplasty (THA) is an effective operation for the restoration of the hip function. The number of operations is steadily climbing and is going to reach new heights in the future. The most devastating complication is the deep infection of the joint and has to be treated with a total revision of the prostheses. The risk factors for an infection play a very important role in the preoperative assessment of the patient and for the antibiotic treatment. There are many different opinions on which risk factors are associated with the development of a deep infection in the literature. Our goal was to analyze and find the risk factors, which matter most in the clinical treatment of patients. We searched the database “PubMed” and “Embase” with the keywords: „ Risk factors associated with a deep infection included the BMI (Body mass index), male gender, prolonged duration of surgery, diabetes mellitus type 2, the ASA (American society of anesthesiologists) score, the Charlson score and the NNIS (National Nosocomial Infections Surveillance System) risk index score. Female gender, age and the diagnosis of rheumatoid arthritis were not associated with deep infections. Patients with risk factors should be assessed preoperatively and receive an appropriate prophylactic antibiotic treatment, to reduce the risk of a deep infection. With the reduction of their weight and adjustment of the diabetes, patients can reduce the risk for infection by their own. Total hip replacement is still a safe and effective operation and thus should not be withheld from patients.
In a prospective randomized study of two groups of 65 patients each, we compared the acetabular component position when usingthe imageless navigation system compared to the freehand conventional technique for cementless total hip arthroplasty. The position of the component was determined postoperatively on computed tomographic scans of the pelvis. There was no significant difference for postoperative mean inclination (p=0.29), but a significant difference for mean postoperativ acetabular component anteversion (p=0.007), for mean deviation of the postoperative anteversion from the target position of 15°(p=0.02) and for the outliers regarding inclination (p=0.02) and anteversion (p<0.05) between the computer-assisted and the freehand-placement group.Material and Methods
Results
This scientific work is a non-interventional, experimental and prospective comparative study of two very high-viscosity PMMA bone cements: Fast-setting PMMA bone cements are used in the endoprothetics of the patella and knee (in Australia) and are also used to cement an artificial acetabulum (in the UK). Are there any differences regarding the characteristics of the two fast-setting PMMA bone cements? All cements were mixed as specified by the manufacturer and analysed on the following parameters: handling properties (mixing, waiting, working and hardening phase), powder/liquid-ratio, mechanical properties (ISO 5833:2002 and DIN 53435), fatigue strength (ISO 16402) and elution profile. All tests were done in an acclimatised laboratory with temperatures set at 23.5°C ± 0.5°C and a humidity of >40%. Of two batch numbers, 11 units of each bone cement were tested.BACKGROUND
MATERIALS AND METHODS
In a recent study we evaluated the clinical and radiographic long-term results as well as the serum metal concentrations of 105 cementless primary total hip prosthesis, performed between November 1992 and May 1994 with a 28-mm high-carbide-concentration metal-on-metal articulating surfaces. Forty-one patients who had had a total of forty-four arthroplasties were available for follow-up evaluation at a minimum of seventeen years postoperatively. The median serum cobalt concentration of the patients with their hip replacement as the only source of cobalt was 0.7 µg/L (range 0.4–5.1µg/L), showing no significant difference to the previous study after a minimum of 10 years follow-up. We were investigating the systemic dissemination, which in turn, did not show more severe effects, such as carcinogenicity or renal failure. There are many complex issues associated with the analysis of metal ions, including collecting technique, analysis and reporting of the results. At the AAOS in March 2013, the Hip Society mentioned, that systemic ion levels are just one factor in the evaluation and should not be relied upon solely to determine the need for revision surgery. Furthermore, the correlation between cobalt or chromium serum, urin or synovial fluid levels and adverse local tissue reactions is incompletely understood. In our present study we evaluated the serum, urin as well as the joint aspirate metal concentrations, of cementless total hip arthroplasties with a high-carbon, metal-on-metal bearing (Metasul®) at a mean of eighteen-years follow-up. We performed a correlation analysis to evaluate the relationship between these values and to determine whether elevated serum metal concentrations are associated with elevated and local metal concentrations and with early failure of metal-on-metal articulations.Introduction
Patients and Methods
Online video is increasingly becoming a key source for people to satisfy their information needs. YouTube is one of the post popular websites used for information exchange, with more than one billion unique visitors every month. In an attempt to participate in personal health decisions related to hip arthritis, patients may access YouTube for further information. As YouTube is a non peer-reviewed platform and little is known about the quality of available videos. We therefore asked the following research questions: (1) What is the information quality of YouTube videos related to the diagnosis of hip arthritis and (2) what information for the treatment of hip arthritis can be found on YouTube?Background
Questions/purposes
Computer Tomography (CT) imaging has been limited to beam hardening artefacts until now. Literature has failed to describe sensitivity and specifity for loosening of endoprothesis in CTs, as metal artefacts have always influenced the diagnostic value of CTs. In recent years a new technology has been developed, the Dual Energy CT. Dual Energy CT scanners simultaneously scan with two tubes at different energy levels, most commonly 100kVp and 140kVp. Furthermore pictures gained from Dual Energy CTs are post-processed with monoenergetic reconstruction, which increases picture quality while further reducing metal artefacts. This promising technology has increased the diagnostic value preventing more radiation for the patients, for example in detection of kidney stones or to map lung perfusion. In the musculoskeletal imaging it has not been established yet and further clinical investigations are necessary. Thus the aim of this study is to describe sensitivity and sensibility for endoprothesis loosening of this novel technology. 53 prospective patients (31 total hip- and 22 total knee-arthoplasties) who were planned for revision surgery underwent preoperative Dual Energy CT examination. All scans were performed with a second-generation, dual-energy multi-detector CT scanner. And all pictures were post-processed with monoenergetic reconstruction. Radiologists were blinded for patient´s history. Senior consultants, who are specialized in arthroplasty of the hip and the knee, performed surgery. Intraoperative information was used as gold standard.Introduction
Material and Methods
Septic arthritis is a therapeutic emergency with a high mortality rate (about 11%)(1). Inadequate treatment can cause permanent joint damage. Management of the septic arthritis includes prompt antibiotic treatment as well as joint-decompression and removal of purulent material(2). It is still discussed controversially and there is little evidence which surgical concept is preferable: arthroscopy with lavage and debridement or open arthrotomy with synovectomy(3,4). The aim of the study was to compare efficacy of arthroscopy and arthrotomy in patients with septic gonarthritis. We evaluated 70 consecutive patients who underwent arthroscopy or arthrotomy at our clinic, because of a bacterial monarthritis of the knee between 2002 and 2010. Our primary outcome was the early recurrence of infection (> 3 months after surgery), which made a second surgery necessary. We compared patients who suffered reinfection and those who did not, in regard to the surgery type as well as potential confounders like comorbidity (measured by Charlson comorbidity index), age, body mass index (BMI), Gächter's -, Kellgren and Lawrence - and Outerbridge classification, duration of symptoms and inflammatory parameters. Furthermore we evaluated differences of the confounders between the surgery groups. From the 70 patients 41 were treated arthroscopic and 29 with arthrotomy. In total eight patients (11.4%) had to undergo a second surgery because of early reinfection. The rate was significantly higher in patients treated with arthrotomy (n=6; 20.7%) compared to those treated with arthroscopy (n=2; 4.9%) (p=0.041). Whereas we found no significant influence of potential confounders between the reinfection group and the group where primary eradication was achieved. Patients who underwent arthrotomy were significantly older, had more comorbidities (both p<0.001) and higher grades of osteoarthritis according to Kellgren and Lawrence classification (p=0.023). In order to adjust the study population towards confounders we performed a subgroup analysis on patients of the second and third age percentile. When we repeated our analysis we still found a significant higher reinfection rate in the arthrotomy group (p=0.036). At the same time there were no differences in prevalence of confounders, neither between the two surgery groups, nor between the reinfection and the primary eradication group. Patients with bacterial monarthritis of the knee who were treated with arthroscopy had a significantly lower reinfection rate than those treated with arthrotomy. As arthroscopy is the less invasive and more sufficient method it should be considered the routine treatment according to our data.
The current investigation includes a retrospective review of the experience of five Institutions with distal femur megaprostheses for tumor over a twenty year period, to analyze the incidence and etiology of failure, using a new classification system based upon the failure modes. Between 1974 and 2008, 2174 patients underwent primary limb preservation for a benign or malignant extremity tumor using a metallic megaprosthesis at five Institutions, 951 (43.7%) were distal femur replacements. Retrospective analysis of complications according to the Letson and Ruggieri Classification was performed and Kaplan-Meier curves of implant survival were defined. Segmental megaprosthetic reconstruction failures were categorized as mechanical and non-mechanical failures.Introduction
Methods
Modular endoprostheses today represent a standard treatment option in the management of musculoskeletal tumors of the lower extremities. Long-term results of these reconstructions, however, are often limited by the course of the underlying disease. We therefore report our experiences in cancer patients with megaprostheses of the lower limb after a minimum of 15 years. 62 patients, 34 men and 28 women, with a mean age of 26 years (median, 20; range, 6–83) were included in this investigation with a mean follow-up of 230 months (median, 228; range, 180–342). Endoprosthetic reconstructions of the proximal femur (11), the distal femur (28), the total femur (2) or the proximal tibia (21) were indicated for osteosarcoma (43), chondrosarcoma (5), malignant fibrous histiocytoma (3) or other tumors (11). All patients have received either a KMFTR (22) or a HMRS (40) modular prosthesis; 23 patients had a muscle flap, 14 had a fibular transposition osteotomy and 4 have received an artificial LARS ligament for soft-tissue reconstruction.Background
Materials and Methods
The rising incidence of atraumatic fractures in patients either with Ewing's sarcoma or osteosarcoma years after chemotherapy revealed a growing population of childhood cancer survivors with a decreased bone mineral density (BMD) possibly due to a long-term effect of the chemotherapy. Therefore we started to screen our patients below 50y of age who were treated for bone malignancies between 1994 and 2009. The first series of measurements included 15 patients – eight Ewing's sarcoma, three female and five male, with a mean age of 18y (±13SD), and seven osteosarcoma, two female and five male, with a mean age of 19y(±9SD). We screened the patients for deficits in their bone status using DEXA (dual-energy-x-ray-absorptiometry) to gain the T-and Z-Scores of the proximal femur and the lumbal spine. Additionally we took blood samples for endocrinological analysis and utilised a questionnaire to scan the patient's liefestyle. The mean time between diagnosis and investigation was 95months (±79SD) in Ewing's sarcoma and 105months (±54 SD) in osteosarcoma. The results of the age and gender matched lumbal measurement (Z-Score) of the Ewing's sarcoma patients showed a reduction of the BMD in six cases (6/8), including three times osteopenia (3/8) and two times osteoporosis (2/8). The osteosarcoma patients presented a BMD-decline in four cases (4/7) with two times osteopenia (2/7) and one osteoporosis (1/7). In the proximal femur six Ewing's sarcoma (6/8) and six osteosarcoma patients (6/7) showed a BMD-decrease including three osteopenic (3/8) and one osteoporotic (1/8) Ewing's sarcoma and four osteopenic osteosarcoma (4/7). We found two cases of pathologic fractures (2/15), one Ewing's sarcoma 29 months after diagnosis with a fracture of the distal femur and the proximal Tibia (1/8) and one osteosarcoma with a fractured distal femur after 72 months (1/7). As presented in our case series osteoporosis after chemotherapy is an underestimated long-term effect of the chemotherapeutic treatment. In our series BMD-reduction seems to be independent of tumour-type and chemotherapeutic agent like MTX.
Accurate and reliable patient information plays a crucial role in the multidisciplinary treatment of malignancies helping to ensure compliance of the patients and their relatives with often long-lasting and stressful treatment. The English version of the online encyclopaedia Wikipedia has been recently reported to be the prominent source of online health information. However, there is little information concerning the quality of information found in Wikipedia. We therefore created a questionnaire concerning of 20 questions asking for scope, completeness and accuracy of information found on osteosarcoma. Three independent observers tested the English version of Wikipedia as well as the patient version and the health professional version of the website of the National Cancer Institute. Answers (scores 0-3) were verified with authoritative resources and international guidelines.Aim
Method
We evaluated the results of surgical one stage versus two stage exchange of patients diagnosed positive for prosthetic infection following total hip replacement in correlation with a classification described by Mc Pherson.
We classified septic revision surgeries following total knee according to a classification published by Mc Pherson. Eradication rate of one stage versus two stage exchange was compared.
Regarding Mc Pherson’s systemic grades classification the eradication rate for two stage exchanges was 85,7% in group A+B and 60%% in group C. One stage procedures achieved 0% eradication rate in group B and 60% in group C. Regarding Mc Pherson’s local extremity grade classification eradication rates within two stage revisions were 84% in group 2 and 75% in group 3. One stage revision achieved 40% and 0%.
In animal experiments antioxidants like Resveratrol, Quercetin-dihydrate and Selen-L-Methionine cause a growth rate decrease in synovial tissue and furthermore an inhibition of pro-infiammatory factors. We investigated the effect of these antioxidants on synovial fibroblasts of Osteoarthritis (OA) patients compared to Rheumatoid Arthritis (RA) patients. Random biopsies of synovial membrane were obtained aseptically from joints of OA and RA patients. After in vitro expansion cells were cultivated until passage three, seeded in 96 well microtiterplates and treated with 0μM, 50μM, 100μM and 200μM of Resveratrol, Quercetin-dihydrate and Selen-L-Methionin. After 24 and 48 hours incubation cell proliferation assays and apoptosis FACS analysis were performed. Additionally woundhealing assays and photographic documentation of resettlement of synovial fibroblasts was accomplished. The results of cell proliferation assays showed a highly significant reduction as well in OA and RA cells. In OA synovial fibroblasts 200μM of Resveratrol evoked a decrease of 72,3 ±1,7% (***), 200 μM of Quercetin-dihydrate induced a reduction of 16,11 ±3% (***). 200μM of Selen-L-Methionine evoked a decrease of 27,3 ±3,8% (***). In RA cultures 200 μM of Resveratrol evoked a decrease of 77,7 ±1,8% (***), 200μM of Quercetin-dehydrate induced a reduction of 20,38 ±15,3%(**), 200μM of Seleno-L-Methionine evoked a decrease of 23,3 ±4,8%(***)(n=20). The results of photographic documentation correlated with cell experiments. Analysis with untreated and treated OA and RA synovial fibroblasts for their content of apoptotic and necrotic cells by Annexin/7AAD staining displayed only few apoptotic cells. Caspase 3, a key mediator of apoptosis, was not activated in resveratrol-treated OA and RA synovial fibroblasts. Resveratrol, Quercetin-dihydrate and Selen-L-Methionine showed a significant growth rate decrease in OA and RA synovial fibroblasts. In OA and RA the pharmacologic treatment with these antioxidants may be a therapeutic approach. Different apoptosis assays represented only few apoptotic cells. We therefore conclude that apoptosis is not the major pathway in resveratrol-treated synovial fibroblasts.
All four patients treated with en bloc resection (primary or secondary) had no recurrence but in two out of that cases a re-operation was necessary because of non union. At a mean follow up from 27 months (4–95) there were no recurrences or metastases at all The flexion/extension of the wrist in currettaged radius was 60° and 80° compared with 38° and 68° in reconstructed radius. The pronation/suppination was 90°/90° in the currettaged ones versus 77°/77° in the allograft replaced ones. The functional outcome evaluated with Mayo Wrist Score and DASH score showed an exellent outcome for both groups (84/7,7 Allograft <
->
85/10 Currettage)
The functional outcome proof no disadvantages in daily life and daily work compared to curettage. Thus allograft reconstruction of the distal radius represents a valuable alternative to arthrodesis.
Despite great progress in implant design, materials and new implantation techniques aseptic loosening is still the most frequent cause of implant failure in THA, which was found to be increased especially in patients with osteonecrosis of the femoral head (ON-FH). While a direct link between aseptic loosening and periprosthetic bone loss still remains elusive, there is plentiful evidence for a close association with early migration of implant components. Although the beneficial effect of bisphonates on periprosthetic bone mass is well established, little is known to date about their effects on implant migration. This is an important issue, because successful prevention of early implant migration would provide strong evidence of a beneficial effect on the survival rate of THA. Previously, Krismer et al. found that a total migration of the cup of ≥ 1mm and a subsidence of ≥ 1.5mm 2 years after surgery was highly predictive for aseptic implant failure of THA within 8 to 10 years. Fifty patients with end-stage ON-FH were consecutively enrolled to receive either 4mg of ZOL or saline solution (CTR) in a double-blind fashion. Radiographs standardized for EBRA-digital analysis were performed at each follow-up exam at 7 weeks, 6 months, 1 year, and yearly thereafter. The minimum follow-up period was 2 years (median follow-up: 2.8 years). Migration of the acetabular and femoral components was analyzed with the EBRA-digital software (University of Inns-bruck, Austria) independently by 3 investigators fully blinded to randomization. Within the placebo group, distal migration of the stem (subsidence) steadily increased up to −1.2mm ± 0.6 SD at 2 years after THA without reaching a plateau phase (P<
0.001, Friedman ANOVA). Less but a nearly curvilinear migration pattern was found for the acetabular components, with a transverse migration of 0.6mm ± 1.0 SD and a vertical migration of 0.6mm ± 0.8 SD at 2 years (P<
0.001, Friedman ANOVA). Treatment with ZOL effectively minimized the migration of cups in both the transverse and vertical direction (0.15 mm ± 0.6 SD and 0.06 mm ± 0.6 SD, respectively, P<
0.05, ANOVA), and a trend to a decreased subsidence was also found for stem migration (−0.91 mm ± 0.51 SD; P=0.11, ANOVA). In addition, total cup migration exceeding 1mm at 2 years was significantly reduced by ZOL in 8 patients (12 vs 4 in CTR vs ZOL, respectively) as was also found in 6 patients for subsidence (≥ 1.5mm in 9 vs 3 patients in CTR vs ZOL, respectively) (P<
0.05, Fisher’s exact). This is the first clinical trial reporting that a single infusion of ZOL suffices to improve initial implant fixation in THA. Based on best evidence available to date, this new concept shows great promise of improving the long-term outcome in THA and should be given attention in long-term trial.
Chevron osteotomy for correction of symptomatic hallux valgus deformity is a widely accepted method. Full weight bearing in regular shoes is not recommended before six weeks after surgery. Low intensity pulsed ultrasound is known to stimulate bone formation leading to more stable callus and faster bony fusion. We performed a randomized, placebo-controlled, double-blinded study on 44 patients (52 feet) who underwent chevron osteotomy to evaluate the influence of daily transcutaneous low intensity pulsed ultrasound (LIPUS) treatment at the site of osteotomy. Follow up at six weeks and one year was done with plain dorsoplantar radiographs, halluxrmetatarsophalangeal-interphalangeal scale and a questionnaire on patient satisfaction. There was no statistical difference concerning all pre- and postoperative clinical features, patient satisfaction and all radiographic measurements (hallux valgus angle, intermetatarsal angle, sesamoid index, metatarsal index) except for the first distal metatarsal articular angle (DMAA). The DMAA showed statistical significant (p=0,046) relapse in the placebo group comparing intraoperative radiographs after correction and fixation (5,2 degrees) and at six weeks follow up (10,6 degrees). Despite potential impact of LIPUS on bone formation we found no clinical evidence for its influence on outcome six weeks and one year after chevron osteotomy for correction of hallux valgus deformity.
Due to the importance of the thyroid treatment it was decided to control the lesion in C6 in close intervals. The lumbar tumour was initially treated outside and the first relapse was marginal resected at our department 11 years after the first diagnosis. The bone alterations appeared radiographically lytic and cystic.
Based on paleopathological findings there is evidence that primary malignant bone und probably soft tissue tumours accompanied mankind from the very beginning. Impressive findings of osteosarcomas have been reported from ancient Peru and medieval Hungary. Astonishingly a report exists on a 3rd century AD amputation of a leg affected by “cancer” and, even more amazing, on the successful reconstruction using a homologous limb transplant. This “miracle” has been attributed to Saints Cosmas and Damian. According to the legenda aurea of Jacobo da Varragine the miraculous treatment of took place in 3rd century Rome. The saints amputated the leg of the Deacon Justinian and successfully transplanted the leg of a black African, who had died some hours ago. According to the legend the deacon was able to walk again and glorify his doctors. This legend inspired artists throughout the centuries as can be seen in a famous 16th century oil painting in Stuttgart’s Landesmuseum Württemberg. The twin saints Cosmas and Damian have been praised before for the first homoplastic limb transplant. The cause for amputation, however, was reported to be a “gangrenous leg” or a “diseased leg”. Looking at the original text of the legenda aurea, a different picture emerges, the cause for surgery being “cancer” of the leg – “…cui cancer unum crus totum còsumpserat”. Also astonishing, at their time and in ours, the saints treated patients without taking any payment. It is not surprising that they were the most renowned of all medically inclined saints and were soon regarded as patron saints of medicine. From today’s medical view, neither resection margins according to Enneking nor a follow-up period were provided by the legenda aurea. It therefore remains elusive whether a local or systemic recurrence occurred. Nevertheless, Saints Cosmas and Damian may well be regarded as Europe’s first orthopaedic oncologists.
Epimetaphyseal lesions may occur within congenital dysplasia or can be linked to metabolic, inflammatory and systemic diseases. They can also be caused by trauma or be due to malign or benign neoplasms. Our case-report concerns a 4-year old boy who was x-rayed the day after falling from a chair and twisting his right ankle. X-ray showed an epimetaphyseal lesion of about 2 cm in diameter, located eccentrically in the lateral site of the distal tibia. A unilamellar periostal reaction could be detected in the lateral slices. On MRI, the lesion seemed to be of chondromatous origin and showed smooth borders with no evidence of surrounding oedema. The adjacent epiphyseal plate appeared as untypically fragmented. In CT-scans, the ventrolateral cortical bone was partially perforated and the lesion showed a tender sclerotic border. Due to the benign aspect, we agreed upon radiologic controls in order not to harm the epiphyseal plate by biopsy. MRI follow-ups revealed a slight but continuous growth. The lesion assumed an increasingly eccentric, tongue-shaped configuration with simultaneously increasing calcifications and mineralisations. After 5 years of radiological surveillance, the patient showed no evidence of growth-disturbance and did not report pain, but an increasing feeling of pressure when wearing boots. Traumatic causes as well as metabolic, inflammatory and systemic diseases can, considering the patient’s history and clinical status, be put aside. The benign aspect combined with the long-term follow-up rules out malignancies. A chondroid matrix with increasing areas of mineralisation imply the diagnosis of a chondromatous tumour, although radiomorphology does not support this assumption; especially not, if age, clinical presentation, eccentric epimetaphyseal location and the involvement of the epiphyseal plate are taken into account. Among the entities left for differential-diagnosis, a dysplastic process e.g. Dysplasia hemimelica, must be considered, although doubts remain. For confirmation of diagnosis, further radiological and clinical surveillance will be conducted.
Chordomas are rare neoplasms originating from notochordal remnants. They usually affect the midline and the standard treatment consists of surgery and radiotherapy. The present study investigates the expression of survivin, DR4 and DR5 to evaluate potential molecular targets for future therapy-strategies. The study-group included 33 chordomas obtained from 21 male and 9 female patients. At time of diagnosis the patients’ age ranged from 24 to 80 years (51.9 ys.). Tumours were located on the scull-base, in the sacral/coccygeal area and the column in 13, 10, and 7 cases, respectively. Tumour-volume, known in 16 cases, ranged from 3.6 to 668.2 cm3 (mean size 130.7cm3). Immunohistochemistry was performed with antibodies against survivin, DR4, DR5. The staining pattern (cytoplasmic and/or nuclear), percentage of positive tumour-cells and staining-intensity were evaluated. Histologically the tumours were classified as classic, chondroid and dedifferentiated chordomas in 27, 2 and 1 case, respectively. Survivin expression was obtained in 87.5% of the cases. The staining pattern was cytoplasmic in all cases and an additional nuclear staining was detected in two. Staining-intensity was predominantly weak. In 87.9% of cases DR4 staining was investigated in more than 10% of the tumour-cells. The immunoreaction was cytoplasmic (87.9%) and a nuclear staining was additionally detected in two cases. The staining-intensity was predominantly weak. In 81.8% of the chordomas DR5 staining was obtained in more than 10% of the tumour-cells. The staining pattern was cytoplasmic (84.4%) and in one case cytoplasmic and nuclear. The staining-intensity was predominantly moderate. We hypothesise, based on the availability of new chemo- or immunotherapeutic agents like Mapatumumab (agonistic human monoclonal antibody to DR4, tested in solid tumours) and YM155 (new small-molecular inhibitor of survivin, tested in solid tumours and lymphoma), that survivin, DR4 and DR5 may act as potential molecular targets in future therapy of chordomas.
Multifocal osteolytic lesions of the skeletal system are a challenge regarding diagnosis especially when multi-nucleated giant cells which are not specific for a tumour entity are found in the histological specimen. Therefore multiple differential diagnosis have to be considered such as metastases, primary malignant bone tumours, multicentric giant cell tumour of bone and brown tumours of primary hyperparathyroidism. A 49 year old woman underwent medical investigation in an external surgical department due to right hip pain after a fall. The radiologic skeletal status surprised with multiple osteolytic pelvic lesions and one tumour in the left scapula and first histological diagnosis described a giant cell tumour of bone with malignant aspects. After confirmation of this diagnosis by a second histopathological inquiry accomplished by a bone tumor specialist the patient was transferred to our tumour centre. To exclude the differential diagnosis of brown tumours a close look on the parathormon level was done which revealed an exorbitantly high serum amount of 922.7 pg/ml (normal 15–65 pg/ml). Further examination confirmed a parathyroid adenoma. After its extirpation serum levels of parathormon decreased and two months after therapy with high dose calcium substitution radiologic controls show a decline of osteolysis with bone consolidation. Brown tumours of hyperparathyroidism have always to be considered as a rare differential diagnosis of multiple giant cell containing tumours. The disease cannot be distinguished by the histological pattern but can very easily be excluded by normal parathormon levels. First step of therapy in brown tumours should be surgical extirpation of parathyroid adenomas or carcinomas followed by an endocrinological regime. Only failure of this treatment requires further surgical stabilisation of the bone lesions.
Giant cell tumor of the distal radius is associated with a high local recurrence rate. En bloc resection of the distal radius and reconstruction using osteoarticular allograft, curettage with PMMA blomb, and allograft arthrodesis are established methods. The aim of the study was to evaluate the functional outcome of our patients with the DASH-Score and the Mayo Wrist score. In the last 7 years six patients were treated at our department due to a giant cell tumor of the distal radius. Two patients were primary treated with an en bloc resection. The other four were primary treated with curettage packing of the defect with polymethylmethacrylate. In two of these cases a secondary en bloc resection was performed for local recurrence. For evaluation of function in daily live we used the DASH score and the MAYO wrist score. The mean bone resection length was 5,25cm (5–6 cm).All four patients treated with en bloc resection (primary or secondary) had no recurrence but in two out of that cases a re-operation was necessary because of non union. At a mean follow up from 27 months (4–95) there were no recurrences or metastases at all. The flexion/extension of the wrist in currettaged radius was 60°/80° compared with 38°/68° in reconstructed radius. The pronation/suppination was 90°/90° in the currettaged ones versus 77°/77° in the allograft replaced ones. The functional outcome evaluated with Mayo Wrist Score and DASH score showed an excellent outcome for both groups (84/7,7 Allograft <
->
85/10 Currettage) Functional outcome of distal radius resection reconstruction using an allograft is highly satisfactory compared with the literature, however we experienced a high risk for pseudoarthrosis. For prevention of non union simultaneous bone grafting at the index operation could be advisable. Thus allograft reconstruction of the distal radius represents a valuable alternative to arthrodesis.
Periprosthetic osteolysis after total joint replacement is a well described complication. This normal slowly increasing process is caused by infection, implant loosening or more special, debris induced. However malignant processes may rarely occur at exact this location too. Based on clinical presentation and imaging it is sometimes difficult to exclude a local malignant process. We report two cases of extensive osteolysis after total hip replacement, including their follow up and a review of the relevant literature. Two female patients developed massive osteolysis in periprosthetic areas (pelvic area and proximal femur as well as distal femur) after being treated by total hip arthroplasty 14 and 18 years ago. In both cases a tumorous process was suspected after imaging and they were therefore referred to our clinic. In one case a rapidly progressing soft tissue swelling with extensive peri-articular osteolysis was considered to be a malignant tumour. After an incisional biopsy, an embolisation had to be performed due to continuous massive bleeding. Histology revealed a superinfected polyethylene disease, treated with a two stage revision surgery. The second patient presented with an impending fracture due an unusual osteolysis at the tip of the stem. Here again polyethylene debris was found at biopsy. Extensive osteolysis and/or soft tissue swelling caused by polyethylene debris may sometimes be difficult to differ from a tumorous process. As a guideline presented by Min WK. et al in 2008 a reactive bone-destroying process normally proceeds slowly in contrast to a more rapid progression in malignant disease. However, as presented in the first of our cases, exemptions may occur. In these cases a biopsy or at least a frozen section at operation should be obtained in order to exclude a real neoplasm.
Increasing incidence rates of soft tissue sarcomas (STS) have been reported. In the present study the authors have analysed the incidence of STS in Austria in a population-based study for the period 1984–2004 in comparison with seven international studies. Age-adjusted incidence rates, gender- and age-predilection and geographic differences were analysed, comprising data from the Austrian National Cancer Registry, including all cases of STS in Austria between 1984 and 2004. A total of 5333 cases was registered, male to female ratio was 0.8. The most common histotypes were sarcoma NOS (36%), leiomyosarcoma (24%), liposarcoma (12%), malignant fibrous histiocytoma (MFH) (9%) and fibrosarcoma (5%). Age-adjusted incidence rate was 2.4 per 100,000 per year. Analysis of annual incidence rates and three-year-periods showed no increasing trend (annual increasing gradient = −0.0025). This study analysed the most recent data from a European population in comparison with seven other studies. An increase of incidence of STS as postulated elsewhere could not be confirmed. The incidence rate of STS in Austria (2.4 per 100 000 per year) ranges in the lower half of international incidence rates (1.8–5.0 per 100 000 per year). Different inclusion criteria (Kaposi’s sarcoma and dermatofibrosarcoma) and classificationsin the various studies could be seen. These findings are more likely to cause the increase of incidence in some studies than true increase of STS due to new or accumulated risk factors.
High-dose methothrexate, a standard agent in the therapy protocols for osteosarcoma, has long been suspected to have a negative long-term effect on bone metabolism and bone mineral density, especially in children and young adults. Recent literature questioned this association as also the BMD of Ewing‘s sarcoma patients treated without methothrexate is known to be decreased. We therefore wanted to screen our patients treated for Ewing‘s sarcoma and osteosarcoma for osteopenia/osteoporosis-associated fractures. Between 1994 and 2008 107 patients below 50y of age were treated for bone malignancies including 51 Ewing’s sarcomas – 31 male and 20 female – with a mean age at diagnosis of 17y(±11SD) and 56 osteosarcomas – 36 male and 20 female – with a mean age of 23y(±12SD). We screened the patients‘ files for fractures after chemotherapy. We found five patients with not trauma-associated fractures – one Ewing‘s sarcoma(1/51;2%) and four osteosarcoma patients(4/56;7%). They presented one fracture of the proximal femur 107 months after tumour diagnosis, three fractures of the distal femur after 29, 51, and 72 months and two fractures of the proximal tibia after 29 and 32 months (one patient suffered from fractures affecting both – the distal femur and the proximal tibia). As presented in our case series fractures due to an osteoporotic process after chemotherapy for bone sarcomas are well known late effects. Although described in several studies therapeutic recommendations for pro-phylaxis are sparse. Furthermore the fact that fractures occurred in both types of sarcoma casts MTX as the main cause of chemotherapy-induced osteoporosis into doubt. Additionally we estimate a high number of unreported cases of premature osteoporosis because sarcoma patients are usually not tested for their BMD-levels. Therefore further studies using DEXA (dual-energy-x-ray-absorptiometry) to measure the patients BMDs after chemotherapy are needed.
Epitheloid haemangioendothelioma is a rare tumour of vascular origin. It is characterised by the appearance of epitheloid endothelial cells and occurs typically in soft-tissue, skin, and liver. Less frequently it is found in bone. The tumour is more often located in the long bones of the lower extremities, and the pelvis than in the upper extremities, vertebral column, and flat bones. The lesion nearly affects all age groups and there is a male predilection.
Epitheloid haemangioendothelioma of bone is a rare tumour and the diagnosis is quite difficult. Metastatic rate is about 20–30% and mortality about 10–20%. As presented in our cases bone involvement could either be attributed to primary haemangioendotheliomas of bone or to metastases of non-osseous forms. As in our cases it has been reported, that predicting prognosis is difcult, however nuclear atypia, mitotic activity, spindling of cells, and necrosis have been reported as negative prognostic factors.
Although fibrous dysplasia is a benign bone disease, in few cases patient are suffering from severe pain of the skeletal system. The aim of this study was to evaluate the current state regarding pain of patients with fibrous dysplasia treated at our hospital. We searched our digital database since 1990 for patients with fibrous dysplasia. Subsequent we verified the histological diagnosis by reviewing the final pathologic report. Additional we called the identified patients by phone to make an enquiry about their pain course and associated treatment. For rating pain intensity we used a numeric rating scale with a range within zero to ten. We identified 43 patients (21 male, 22 female) with an average age at initial diagnosis of 40 years (range 10 to 72years). The mean follow up was 6 years (range 1 to 23 years). Among these 43 patients we were able to contact 33 by phone. Initial diagnosis was made due to pain in 23 cases, nearly coequal by coincidental examination in 20 cases, for fracture in two cases and for local swelling and bone deformity each time in two cases. Thirty-six patients revealed monostotic and seven patients polyostotic involvement. The following locations were found: three times craniofacial, four times within the spine, eight times at the upper extremity, ten times in the pelvis and 31 times at the lower limb. Two patients were suffering additionally from Mazabraud Syndrome. Actual values at the numeric rating scale regarding pain ranged from 0 to 9 with a mean value of 1. Specific in the polyostotic group we found an average value of 3 and three of seven patients stated a value greater than 5 for persistent pain. Five patients with polyostotic involvement were treated with bisphosphonat for pain control with good response. It is remarkable that patients with polyostotic involvement have marked higher values for pain intensity at the numeric rating scale. So therefore we should have a closer look for potential reasons explaining that fact. In accordance with previous published studies we found that pain decreased by intermittent intravenous application of bisphosphonates.