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Purpose: The aim of this study was to evaluate the development of the worldwide survival rate of primary total hip arthroplasty (THA). The hypothesis was that survival improved over the last decade in worldwide arthroplasty registers. Methods: THA registers were screened in 2022 and compared between different countries with respect to the number of primary implantations per inhabitant, age, fixation type, and survival rate, and compared to similar data from 2009. The data from these reports were analyzed in terms of number, age distribution, and procedure type of primary THAs. Survival curves and a comparative analysis with respect to the development over time were calculated. Results: We identified nine hip arthroplasty registers that contained sufficient data to be included. A large variation was found in the annual number of primary THA implantations per inhabitant, with more than the factor 4 for all age groups across regions. The procedure type varied strongly as well, e.g. in Sweden, 50% were cemented THAs, whereas in Emilia-Romagna (Italy), 96% of THAs were implanted cementless. We found an improved survival rate of 5%, with 90% of survival after 15 years in the cohorts from 2021 compared to 85% in the cohorts from 2009. Conclusion: The present study revealed a significant improvement in the survival of THA in worldwide arthroplasty registers within different countries and regions over the period of one decade. We believe that it is safe to state that the success of THA is still rising with respect to this main outcome.

Aims: Patients with proximal femoral fractures (PFFs) are often multimorbid, thus unplanned readmissions following surgery are common. We therefore aimed to analyze 30-day and one-year readmission rates, reasons for, and factors associated with, readmission risk in a cohort of patients with surgically treated PFFs across Austria. Methods: Data from 11,270 patients with PFFs, treated surgically (osteosyntheses, n = 6,435; endoprostheses, n = 4,835) at Austrian hospitals within a one-year period (January to December 2021) was retrieved from the Leistungsorientierte Krankenanstaltenfinanzierung (Achievement-Oriented Hospital Financing). The 30-day and one-year readmission rates were reported. Readmission risk for any complication, as well as general medicine-, internal medicine-, and surgery/injury-associated complications, and factors associated with readmissions, were investigated. Results: The 30-day and one-year readmission rates due to any complication were 15% and 47%, respectively. The 30-day readmission rate (p = 0.001) was higher in endoprosthesis than osteosynthesis patients; this was not the case for the one-year readmission rate (p = 0.138). Internal medicine- (n = 2,273 (20%)) and surgery/injury-associated complications (n = 1,612 (14%)) were the most common reason for one-year readmission. Regardless of the surgical procedure, male sex was significantly associated with higher readmission risk due to any, as well as internal medicine-associated, complication. Advanced age was significantly associated with higher readmission risk after osteosynthesis. In both cohorts, treatment at mid-sized hospitals was significantly associated with lower readmission risk due to any complication, while prolonged length of stay was associated with higher one-year readmission risks due to any complication, as well as internal-medicine associated complications. Conclusion: Future health policy decisions in Austria should focus on optimization of perioperative and post-discharge management of this vulnerable patient population. Cite this article: Bone Jt Open 2024;5(4):294–303.

Abstract Objective We aim to evaluate the efficacy of CT-guided percutaneous radiofrequency ablation (RFA) and surgical treatment in osteoid osteoma (OO) treated at the Medical University of Graz. Materials and methods In a single-institution study, we analysed data from January 2005 to January 2021 of patients with histological/radiological diagnosis of OO. CT and MRI scans were reviewed for typical findings. Means (with SD) and medians (with IQR) were reported for normally and non-normally distributed variables. Differences between groups were assessed using chi-squared tests and t-tests. Results One hundred nineteen patients (mean age: 21.6 ± 10.9 years; 63.9% males) with confirmed OO were retrospectively evaluated. 73 and 43 patients underwent RFA and surgery, respectively. In three cases, RFA combined with surgery was performed. Pre-intervention, 103 patients (88.8%) had undergone CT, and 101 had an MRI (87.1%). The nidus was confirmed in 82.5% of cases with CTs (85/103) and 63.4% with MRIs (64/101). The majority of nidi were located cortically (n = 96; 82.8%), most frequently in the femur (38 patients, 33.3%) with a median size of 8.0 mm (IQR: 5.0–12.0 mm). Median symptom duration before treatment was 6.0 (IQR: 4.0–13.0) months. The complication rate was 12.1% (14/116; 15.1% RFA vs. 7.0% surgery; p = 0.196). In total, 11.2% of patients had persistent symptoms after one week with clinical success rates of RFA and surgery, 86.3% and 90.7% (p = 0.647), respectively. Conclusion Compared to surgical treatment, CT-guided percutaneous RFA is a safe, minimally invasive, reliable, and efficient treatment option for OO. Critical relevance statement This article critically assesses the diagnosis and treatment of osteoid osteoma, emphasising accurate imaging, and detailing a non-invasive option for effective management. Key points • This study analyses 116 cases of OO at one institution, focusing on symptom persistence, recurrence in short-term follow-up, and complications in two study groups. • Surgery showed higher, though not statistically significant, success despite comparable symptom persistence; CT displayed typical OO features more than MRI, regardless of the intramedullary, cortical and subperiosteal location as well as the site of the affected bone. • CT-guided RFA is an effective therapeutic alternative for OO compared to surgical intervention. In case of atypical OO appearance, RFA is not the first-line treatment. Graphical Abstract

IntroductionSince its introduction in November 2022, the artificial intelligence large language model ChatGPT has taken the world by storm. Among other applications it can be used by patients as a source of information on diseases and their treatments. However, little is known about the quality of the sarcoma-related information ChatGPT provides. We therefore aimed at analyzing how sarcoma experts evaluate the quality of ChatGPT’s responses on sarcoma-related inquiries and assess the bot’s answers in specific evaluation metrics.MethodsThe ChatGPT responses to a sample of 25 sarcoma-related questions (5 definitions, 9 general questions, and 11 treatment-related inquiries) were evaluated by 3 independent sarcoma experts. Each response was compared with authoritative resources and international guidelines and graded on 5 different metrics using a 5-point Likert scale: completeness, misleadingness, accuracy, being up-to-date, and appropriateness. This resulted in maximum 25 and minimum 5 points per answer, with higher scores indicating a higher response quality. Scores ≥21 points were rated as very good, between 16 and 20 as good, while scores ≤15 points were classified as poor (11–15) and very poor (≤10).ResultsThe median score that ChatGPT’s answers achieved was 18.3 points (IQR, i.e., Inter-Quartile Range, 12.3–20.3 points). Six answers were classified as very good, 9 as good, while 5 answers each were rated as poor and very poor. The best scores were documented in the evaluation of how appropriate the response was for patients (median, 3.7 points; IQR, 2.5–4.2 points), which were significantly higher compared to the accuracy scores (median, 3.3 points; IQR, 2.0–4.2 points; p = 0.035). ChatGPT fared considerably worse with treatment-related questions, with only 45% of its responses classified as good or very good, compared to general questions (78% of responses good/very good) and definitions (60% of responses good/very good).DiscussionThe answers ChatGPT provided on a rare disease, such as sarcoma, were found to be of very inconsistent quality, with some answers being classified as very good and others as very poor. Sarcoma physicians should be aware of the risks of misinformation that ChatGPT poses and advise their patients accordingly.

Abstract Background Enchondromas (EC) and atypical cartilaginous tumours (ACT) of the knee joint represent benign/intermediate chondromatous neoplasms of the bone that are most commonly discovered incidentally. Based on small to intermediate-sized cohorts, the prevalence of cartilaginous tumours of the knee as visible in MRI is estimated at 0.2–2.9%. This study aimed at verifying/challenging these numbers via retrospective examination of a larger, uniform patient cohort. Methods Between 01.01.2007 and 01.03.2020, 44,762 patients had received an MRI of the knee for any indication at a radiologic centre. Of these, 697 patients presented with MRI reports positive for cartilaginous lesions. In a three-step workflow, 46 patients were excluded by a trained co-author, a radiologist and an orthopaedic oncologist, as wrongly being diagnosed for a cartilage tumour. Results Of 44,762 patients, 651 presented with at least one EC/ACT indicating a prevalence of 1.45% for benign/intermediate cartilaginous tumours of the knee joint (EC: 1.4%; ACTs: 0.05%). As 21 patients showed 2 chondromatous lesions, altogether 672 tumours (650 ECs [96.7%] and 22 ACTs [3.3%]) could be analysed in terms of tumour characteristics: With a mean size of 1.6 ± 1.1 cm, most lesions were located in the distal femur (72.9%), in the metaphysis of the respective bone (58.9%) and centrally in the medullary canal (57.4%). Conclusions This study revealed an overall prevalence of 1.45% for cartilage lesions around the knee joint. Whilst a constant increase in prevalence was found for ECs over 13.2 years, prevalence remained constant for ACTs.

Abstract Background Perioperatively administered (leukocyte reduced) allogeneic red blood cell transfusions (lrRBCTs) may lead to transfusion‐related immunomodulation and reduced overall survival (OS) in cancer patients. Herein, the effect of lrRBCT on local recurrence (LR), distant metastasis (DM), and OS in soft tissue sarcoma (STS) patients was analysed. Methods Retrospective study on 432 STS patients (mean age: 60.0 ± 17.8 years; 46.1% female), surgically treated at a tertiary tumour centre. Uni‐ and multivariate survival models were calculated to analyse impact of perioperative lrRBCTs on LR, DM, OS. Results Perioperatively, 75 patients (17.4%) had received lrRBCTs. Older patients, deep, large, lower limb STS rather required lrRBCTs (all p

Abstract Background The preservation or restoration of hip geometry following total hip arthroplasty (THA) is of importance, considering that alterations in the centrum-collum-diaphysis (CCD)-angle, femoral offset (FO), acetabular offset (AO) and total offset (TO) change hip biomechanics. Therefore, the most suitable implant should be used. The aim of this study was to compare the ability of two short-stem-systems and one straight-stem-system to reconstruct hip geometry. Methods Two-hundred-fifty-one patients (mean age: 62.0 ± 10.0 years; 51.8% males) undergoing THA with three different stem types were retrospectively included, after excluding 11 patients with missing radiological follow-up. Pre- and postoperative radiographic images (group I, ANA.NOVA Alpha Schaft Proxy®, ImplanTec, 12 options: n = 99; group II, Optimys® Mathys, 24 options: n = 62; group III: Corail®-System, DePuy-Synthes, 76 options: n = 90) were analyzed. Differences in pre- and postoperative hip geometry (i.e. CCD, FO, AO, TO) were compared between groups with one-way-analysis-of-variance (ANOVA), and post-hoc t-tests. Results The CCD-angle increased by a mean of 8.4° ± 7.2° from pre-to postoperative, with no significant difference between groups (p = 0.097). Significantly larger increases in FO were observed for groups II (4.1 mm ± 7.8 mm) and III (4.9 ± 7.2 mm), in comparison to group I (1.6 ± 6.9 mm; p = 0.006). AO decreased by a mean of 2.2 ± 4.5 mm, with the largest decrease observed in group III (-3.3 ± 5.3 mm), and the smallest for group I (-1.4 ± 3.6 mm; p = 0.011). There was no significant difference in change of TO between groups (p = 0.177). Conclusions Reconstruction of hip geometry using a single-version novel short-stem-system is achievable with comparable results to stem-systems offering multiple options.

Abstract Cementless calcar-guided femoral short stems in total hip arthroplasty (THA) have become increasingly popular over the years. Early distal migration of femoral stems measured by Einzel-Bild-Roentgen Analyse, Femoral Component Analyse (EBRA-FCA) has been reported to be a risk factor for aseptic loosening. The aim of this study was to analyse axial migration behavior and subsidence of a new short stem (launched in 2015) over a follow-up period of 3 years. According to the study protocol, 100 hip osteoarthritis patients who consecutively received an unilateral cementless calcar-guided short stem (ANA.NOVA proxy) at a single department were prospectively included in this mid-term follow-up study. Thirteen patients were lost to follow-up, resulting in 87 patients with unilateral THA who fulfilled the criteria for migration analysis with EBRA-FCA. The cohort comprised 41 males (mean age: 60 ± 16.5; mean BMI (Body Mass Index): 30 ± 13) and 46 females (mean age: 61 ± 15.5; mean BMI: 27 ± 10). Seven standardized radiographs per patient were analyzed with EBRA-FCA. An average migration of 2.0 mm (0.95–3.35) was observed within the first 3 years. The median increase during the first year was higher than in the second and third year (1.2 mm [IQR: 0.5–2.15] vs. 0.3 mm [IQR: 0.1–0.6 mm] vs. 0.25 mm [IQR: 0.1–0.5 mm]. Detected migration did not lead to stem loosening, instability, dislocation, or revision surgery in any patient. A higher risk for subsidence was observed in male and heavyweight patients, whereas the female gender was associated with a lower risk. No correlation between migration and revision could be observed. Although moderate subsidence was detectable, the performance of the short stem ANA.NOVA proxy is encouraging. Yet, its use may be re-considered in overweight and male patients due to more pronounced subsidence.

Soluble urokinase plasminogen activator receptors (suPARs) are a biomarker for inflammatory diseases. This study aims to investigate its diagnostic properties regarding periprosthetic joint infections (PJI). This retrospective cohort study included adult patients who underwent joint puncture for suspected PJI. The presence of PJI was determined according to the criteria of the European Bone and Joint Infection Society (EBJIS). Laboratory study analyses included the determination of white blood cells (WBC) in whole blood, C-reactive protein (CRP) in blood plasma, and suPAR in both blood plasma and synovial fluid. Appropriate diagnostic cut-off values were identified utilizing Youden’s J, and their diagnostic performance was determined by calculating the positive (PPV) and negative predictive value (NPV) for each marker. Sixty-seven cases were included in the final analysis. Forty-three samples (64%) were identified as periprosthetic joint infection (PJI) and twenty-four specimen (36%) were PJI negative cases. The PPV and NPV were 0.80 and 0.70 for synovial suPAR, 0.86 and 0.55 for CRP, 0.84 and 0.31 for WBC and 1.00 and 0.31 for plasma suPAR. Synovial suPAR showed a solid diagnostic performance in this study and has the potential to be an alternative or complementary biomarker for PJI. Further investigations in larger patient collectives are indicated.

Abstract Silver-coated megaprostheses are considered to reduce infection rate following reconstruction of bone defects in tumour surgery or revision arthroplasty. However, little is known about systemic silver exposure and possible side effects. The aim of this study was to analyse serum silver concentrations in patients with silver-coated megaprostheses over a prolonged time period. Between 2004 and 2016, 46 patients (52.2% female, mean age at surgery 47.1 ± 24.2 years) received silver-coated megaprostheses for septic (n = 26) or oncological (n = 17; main implant since 2013) indications, or aseptic loosening (n = 3). Blood was drawn from all patients within the first few days following surgery (without silver ion levels) and thereafter every 6 months at the outpatient department (with silver ion levels). Inductively coupled plasma mass spectrometry was used to determine silver ion levels. Median follow-up was 47.3 months (IQR: 16.1–78.9). Overall, 29 revision surgeries became necessary in 20 patients, equivalent to a cumulative complication rate of 63.0%. Revisions were most commonly for periprosthetic joint infections (PJIs, n = 12) and instability/soft tissue problems (n = 10). Revision-free implant survival was 81.4%, 42.3% and 35.2% at one, 5 and 10 years. Incidence of local argyria was 8.7% (n = 4). Silver ion levels at two or more consecutive time points during follow-up were available for 26 patients. An increment of silver levels within the first months (“run-in”) was observed, followed by an unspecific undulating course. Median initial and latest follow-up (median, 49.5 months) serum silver ion levels were 16.0 ppb (IQR: 9.1–29.1) and 7.4 ppb (IQR: 2.7–14.1), respectively. According to the multivariate mixed linear random-effects model, development of PJI was associated with significantly higher silver ion levels over time (p = 0.002), irrespective of time from surgery (p = 0.274). In the current series, a cumulative complication rate of 63.0% was observed for patients receiving silver-coated megaprostheses for septic of oncological indications. An overall unspecific course of silver ion concentration was present. Development of PJI was significantly associated with increased silver ion levels over time. Yet, no systemic complication associated to high silver levels occurred. It can be concluded that silver-coated implants constitute a safe solution for megaprosthetic reconstruction, but monitoring of silver concentrations is recommended.

Abstract Background Although chondrosarcoma is the second most common primary malignant bone tumor, treatment options are limited due to its extensive resistance to a chemo- and radiation therapy. Since shikonin has shown potent anticancer activity in various types of cancer cells, it represents a promising compound for the development of a new therapeutic approach. Methods The dose-relationships of shikonin and its derivatives acetylshikonin and cyclopropylshikonin on two human chondrosarcoma cell lines were measured using the CellTiter-Glo®. The changes in the cell cycle were presented by flow cytometry. Protein phosphorylation and expression apoptotic markers, MAPKs and their downstream targets were analyzed using western blotting and gene expression were evaluated using RT-qPCR. Results Chondrosarcoma cells showed a dose-dependent inhibition of cell viability after treatment with shikonin and its derivatives, with the strongest effect for shikonin and IC50 values of 1.3 ± 0.2 µM. Flow cytometric measurements revealed a G2/M arrest of the cells after treatment. Protein and gene expression analysis demonstrated a dose-dependent downregulation of survivin and XIAP, and an upregulation of Noxa, γH2AX, cleaved caspase-8, -9, -3, and -PARP. Furthermore, the expression of various death receptors was modulated. As MAPK signaling pathways play a key role in tumor biology, their phosphorylation pattern and their corresponding downstream gene regulation were analyzed. Treatment with shikonin derivatives caused an inhibition of pSTAT3 and an increase of pAKT and the MAPKs pERK, pJNK, and pp38 in a dose-dependent manner. Conclusions These data demonstrated the significant anti-tumorigenic effect of shikonin derivatives in chondrosarcoma and encourage further research.

Background and purpose: Thumb carpometacarpal (TCMC) osteoarthritis is a common condition that causes pain and functional limitations. We compared the outcomes of 2 surgical procedures for TCMC osteoarthritis, the Epping resection-suspension arthroplasty and the double-mobility TCMC prosthesis, and focused on pain relief, functional outcomes, and patient quality of life. Patients and methods: Over a 7-year period a randomized controlled trial including 183 cases of TCMC osteoarthritis was conducted comparing a double mobility TCMC prosthesis (Moovis, Stryker, Kalamazoo, MI, USA) with the Epping resection-suspension arthroplasty. Pre- and postoperative examinations included the range of motion (ROM), SFMcGill score, visual analogue scale (VAS), the disabilities of the arm, shoulder and hand questionnaire (DASH), and the hospital anxiety and depression scale (HADS). Results: At the 6-week postoperative follow-up, significant differences were found in VAS: Epping median 4.0 (interquartile range [IQR] 2.0–5.0) vs. TCMC prosthesis 2.0 (IQR 0.25–4.0), p = 0.03, effect size (area under the curve [AUC]) 0.64 (95% confidence interval [CI] 0.55–0.73), in DASH score: Epping 61 (IQR 43–75) vs. TCMC prosthesis 45 (IQR 29–57), p < 0.001, AUC 0.69 (CI 0.61– 0.78), and in radial abduction: Epping 55 (IQR 50–60) vs. TCMC prosthesis 62 (IQR 60–70), p = 0.001, AUC 0.70 (CI 0.61–0.79). No significant group differences were found at the 6- and 12-months follow-up. During the follow-up period, 3 of 82 prostheses had to be revised but there was no revision in the Epping group. Conclusion: The double mobility TCMC prosthesis had superior outcomes compared with the Epping procedure at 6 weeks; however, there were no significant differences in outcomes at 6 months and 1 year postoperatively. The implant survival rate of 96% after 12 months was acceptable

Abstract Background Despite numerous scientific investigations, the tribological advantages of mobile bearing inserts have not been sustainably confirmed or refuted for modern knee prostheses in clinical studies. The purpose of this study was to compare fixed and mobile bearing inserts in order to draw conclusions regarding clinical benefits. Methods The present prospective single center cohort study of 2 non-randomized stratified groups consisted of 67 patients. All included patients received cemented total knee arthroplasty (Attune®) due to osteoarthritis. 34 patients were treated with a mobile and 33 patients with a fixed insert. The WOMAC score and the Visual Analogue Scale was used for the subjective assessment of success, while the Knee-Society-Score was used considering the Range of Motion for the objective assessment. The subjective and the clinical scores showed improvements for both compared groups postoperatively at 2 years of minimum follow-up. Results The overall postoperative results of the WOMAC score, the Knee-Society-Score and the Visual Analogue Scale presented no statistically difference between the compared groups (p > 0,05). The postoperative ROM showed a superior improvement of 13.2° ± 18.4° in the mobile-bearing group versus 4.9° ± 18.4° (p = 0.017) in the fixed-bearing group. The flexion of the knee joint was 114° ± 10.1° for the mobile-bearings and 109.2° ± 7.2° for fixed bearings (p = 0.012). Conclusion According to the findings, both inserts showed overall promising postoperative results, in terms of objective as well as subjective parameters, without clinically relevant significant differences, except for ROM, which was superior in the mobile bearing group. The present clinical trial has been registered at the ISRCTN registry with the reverence number ISRCTN15117998 on 04/04/2022.

This study aimed to analyse and compare the vancomycin elution kinetics of four biodegradable, osteoconductive antibiotic carriers used in clinical practice within a 42-day in vitro setting. Carriers A and D already contained vancomycin (1.1 g and 0.247 g), whereas carriers B and C were mixed with vancomycin according to the manufacturer’s recommendations (B: 0.83 g and C: 0.305 g). At nine time points, 50% (4.5 mL) of the elution sample was removed and substituted with the same amount of PBS. Probes were analysed with a kinetic microparticle immunoassay. Time-dependent changes in vancomycin concentrations for each carrier and differences between carriers were analysed. Mean initial antibiotic levels were highest for carrier A (37.5 mg/mL) and lowest for carrier B (5.4 mg/mL). We observed time-dependent, strongly negative linear elution kinetics for carriers A (−0.835; p < 0.001), C (−0.793; p < 0.001), and D (−0.853; p < 0.001). Vancomycin concentrations increased from 48 h to 7 d and dropped thereafter in carriers C and D whilst constantly decreasing at any time point for carrier A. Carrier B showed a shallower decrease. Mean antibiotics levels at 42 d were 1.5 mg/mL, 2.6 mg/mL, 0.1 mg/mL, and 0.1 mg/mL for carriers A, B, C, and D. Differences in mean initial and final vancomycin concentrations for carrier A were significantly larger in comparison to C (p = 0.040). A carrier consisting of allogenic bone chips showed the highest vancomycin-to-carrier ratio and the largest elution over the study period. Whilst vancomycin concentrations were still measurable at 42 days for all carriers, carrier A provided a higher drug-to-carrier ratio and a more consistent antibiotic-releasing profile.

Abstract Background Total hip arthroplasty (THA) is the most successful orthopaedic surgery of the past century. The current study aimed to compare the accuracy of digital planning using 2D versus 3D templating. Materials and methods Ninety-five THAs in 90 patients were included in the current study. Pre- and post-operative X-rays (in two planes) and low-dose rotation computed tomography scans from hip to foot were performed. Paired t-test and regression analyses were conducted to compare 2D and 3D templating accuracy of the definitive implant. Results Cup size planned both with 2D (p

Aim Internal fixation of femoral neck fractures is a widely used procedure that is comparatively less invasive and faster than hip replacement. While head preserving internal fixation of these fractures are still preferred where feasible, a faster recovery and lower reoperation rates make arthroplasty increasingly more appealing, in spite of being a more invasive option. Our aim was to determine the reoperation rate after internal fixation at our institution and to explore relevant risk factors in a geriatric population. Methods This monocentric follow-up study was conducted analyzing 116 patients aged 65 and older with femoral neck fractures who were surgically treated with either cancellous screws or dynamic hip screws between 2010 and 2017. We retrospectively collected longitudinal data from our patient database, supplemented by a telephone survey, with a follow-up period of at least 18 months. Results Twenty reoperations, due to either a failure of fixation, avascular necrosis, or posttraumatic osteoarthritis, were identified in our cohort, which constituted a reoperation rate of 17.2% (20/116). Fracture displacement was significantly associated with the reoperation risk (HR 8, CI 3-20; P < .001). The reoperation rate was 52.2% in displaced fractures vs 8.9% in undisplaced fractures. No link was found between the reoperation rate and gender, age, BMI, ASA score, type of implant, quality of internal fixation, type of living accommodation, and pre-fracture mobility. Conclusion Internal fixation has been found to be an effective option in elderly patients with undisplaced fractures regardless of their specific age, cognitive ability or physical condition. In displaced fractures the reoperation rate was found to be high, therefore a primary hip replacement should be recommended.

Abstract The aims of this study were to (1) assess reliability of leg length discrepancy (LLD) measurements at different anatomical landmarks, (2) longitudinally investigate LLD in patients within the first year following total hip arthroplasty (THA) and to (3) correlate changes in LLD with functional outcome. Ninety-nine patients with short stem THA (53.3% males, mean age: 61.0 ± 8.1 years) were prospectively included. Upright pelvic anteroposterior (a.p.) radiographs taken at 6 timepoints (preoperatively, discharge, 6, 12, 24, 52 weeks postoperatively) were used to assess LLD at 5 anatomical landmarks (iliac crest, upper sacroiliac joint, lower sacroiliac joint, tear drop figure, greater trochanter). WOMAC and Harris Hip Score (HHS) were obtained preoperatively and at 6 and 52 weeks. LLD measures significantly increased in the initial phase following THA, from discharge to 6 weeks postoperatively and remained constant thereafter. Documentation of LLDs is dependent on measurement site: LLDs varied significantly between trochanter and iliac crest to tear drop figure (p

Abstract Although particle therapy with protons has proven to be beneficial in the treatment of chondrosarcoma compared to photon-based (X-ray) radiation therapy, the cellular and molecular mechanisms have not yet been sufficiently investigated. Cell viability and colony forming ability were analyzed after X-ray and proton irradiation (IR). Cell cycle was analyzed using flow cytometry and corresponding regulator genes and key players of the DNA repair mechanisms were measured using next generation sequencing, protein expression and immunofluorescence staining. Changes in metabolic phenotypes were determined with nuclear magnetic resonance spectroscopy. Both X-ray and proton IR resulted in reduced cell survival and a G2/M phase arrest of the cell cycle. Especially 1 h after IR, a significant dose-dependent increase of phosphorylated γH2AX foci was observed. This was accompanied with a reprogramming in cellular metabolism. Interestingly, within 24 h the majority of clearly visible DNA damages were repaired and the metabolic phenotype restored. Involved DNA repair mechanisms are, besides the homology directed repair (HDR) and the non-homologous end-joining (NHEJ), especially the mismatch mediated repair (MMR) pathway with the key players EXO1, MSH3, and PCNA. Chondrosarcoma cells regenerates the majority of DNA damages within 24 h. These molecular mechanisms represent an important basis for an improved therapy.

Background and purpose — Cat scratch disease (CSD) is a self-limiting disease caused by Bartonella (B.) henselae. It is characterized by granulomatous infection, most frequently involving lymph nodes. However, it can present with atypical symptoms including musculoskeletal manifestations, posing a diagnostic challenge. We describe the prevalence and demographics of CSD cases referred to a sarcoma center, and describe the radiological, histological, and molecular findings. Patients and methods — Our cohort comprised 10 patients, median age 27 years (12–74) with clinical and radiological findings suspicious of sarcoma. Results — 7 cases involved the upper extremities, and 1 case each involved the axilla, groin, and knee. B. henselae was found in 6 cases tested using polymerase chain reaction and serology in 5 cases. 9 cases were soft tissue lesions and 1 lesion involved the bone. 1 patient had concomitant CSD with melanoma metastasis in enlarged axillary lymph nodes. On MRI, 5 soft tissue lesions were categorized as probably inflammatory. In 3 cases, with still detectable lymph node structure and absent or initial liquefaction, the differential diagnosis included lymph node metastasis. A sarcoma diagnosis was suggested in 4 cases. The MRI imaging features of the bone lesion were suspicious of a bone tumor or osteomyelitis. Interpretation — Atypical imaging findings cause a diagnostic challenge and the differential diagnosis includes malignant neoplasms (such as sarcoma or carcinoma metastasis) and other infections. The distinction between these possibilities is crucial for treatment and prognosis.

Magnesium alloys have recently become the focus of research, as these implants exhibit suitable biocompatibility and appropriate mechanical properties (Grün et al., 2018 [1]).Through intensive preclinical and clinical investigation, many questions regarding stability, biocompatibility and degradation behavior have been answered (Holweg et al., 2020 [2]). This case report aims to describe handling of these implants in a revision situation, especially when located in situ. To describe available options and relevant considerations, including planning and implementation, a revision surgery of a healed medial malleolus fracture is presented. A medial malleolus fracture was primarily treated by a trauma surgeon with two magnesium screws. Due to an osteochondral lesion of the talus, a revision surgery with osteotomy of the medial malleolus was necessary after 17 months. In this revision, conventional screw removal was not possible due to the degradation of the implant. Taking the degradation and the yield strength of the implant into account, we have chosen on the one hand to over-drill and on the other to leave and perforate the screw.To the best of our knowledge, this is the first case study focusing on the clinical intraoperative site of human bone stabilized with magnesium screws. Despite the hydrogen gas production that occurs during degradation, a solid bone-to-implant interface was evident. With this report, we want to encourage the surgical user to get more involved with resorbable magnesium implants.

Particle therapy (PT) that utilizes protons and carbon ions offers a promising way to reduce the side effects of radiation oncology, especially in pediatric patients. To investigate the influence of PT on growing bone, we exposed an organotypic rat ex vivo femur culture model to PT. After irradiation, histological staining, immunohistochemical staining, and gene expression analysis were conducted following 1 or 14 days of in vitro culture (DIV). Our data indicated a significant loss of proliferating chondrocytes at 1 DIV, which was followed by regeneration attempts through chondrocytic cluster formation at 14 DIV. Accelerated levels of mineralization were observed, which correlated with increased proteoglycan production and secretion into the pericellular matrix. Col2α1 expression, which increased during the cultivation period, was significantly inhibited by PT. Additionally, the decrease in ColX expression over time was more pronounced compared to the non-IR control. The chondrogenic markers BMP2, RUNX2, OPG, and the osteogenic marker ALPL, showed a significant reduction in the increase in expression after 14 DIV due to PT treatment. It was noted that carbon ions had a stronger influence than protons. Our bone model demonstrated the occurrence of pathological and regenerative processes induced by PT, thus building on the current understanding of the biological mechanisms of bone.

BackgroundTreatment stratification and response assessment in pediatric sarcomas has relied on imaging studies and surgical/histopathological evidence of vital tumor cells. Such studies and evidence collection processes often involve radiation and/or general anesthesia in children. Cell-free circulating tumor DNA (ctDNA) detection in blood plasma is one available method of so-called liquid biopsies that has been shown to correlate qualitatively and quantitatively with the existence of vital tumor cells in the body. Our clinical observational study focused on the utility and feasibility of ctDNA detection in pediatric Ewing sarcoma (EWS) as a marker of minimal residual disease (MRD).Patients and methodsWe performed whole genome sequencing (WGS) to identify the exact breakpoints in tumors known to carry the EWS-FLI1 fusion gene. Patient-specific fusion breakpoints were tracked in peripheral blood plasma using digital droplet PCR (ddPCR) before, during, and after therapy in six children and young adults with EWS. Presence and levels of fusion breakpoints were correlated with clinical disease courses.ResultsWe show that the detection of ctDNA in the peripheral blood of EWS patients (i) is feasible in the clinical routine and (ii) allows for the longitudinal real-time monitoring of MRD activity in children and young adults. Although changing ctDNA levels correlated well with clinical outcome within patients, between patients, a high variability was observed (inter-individually).ConclusionctDNA detection by ddPCR is a highly sensitive, specific, feasible, and highly accurate method that can be applied in EWS for follow-up assessments as an additional surrogate parameter for clinical MRD monitoring and, potentially, also for treatment stratification in the near future.

Abstract Background Extra-abdominal desmoid tumor fibromatosis (DTF) is a rare, locally aggressive soft tissue tumour. The best treatment modality for this patient cohort is still object of debate. Questions/purpose This paper aimed to (1) to compare the outcomes of DTF after different treatment modalities, (2) to assess prognostic factors for recurrence following surgical excision, and (3) to assess prognostic factors for progression during observation. Methods This was a retrospective multicenter study under the patronage of the European Musculoskeletal Oncology Society (EMSOS). All seven centres involved were tertiary referral centres for soft tissue tumours. Baseline demographic data was collected for all patients as well as data on the diagnosis, tumour characteristics, clinical features, treatment modalities and whether they had any predisposing factors for DTF. Results Three hundred eighty-eight patients (240 female, 140 male) with a mean age of 37.6 (±18.8 SD, range: 3–85) were included in the study. Two hundred fifty-seven patients (66%) underwent surgical excision of ADF, 70 patients (18%) were observed without therapy, the residual patients had different conservative treatments. There were no significant differences in terms of tumour recurrence or progression between the different treatment groups. After surgical excision, younger age, recurrent disease and larger tumour size were risk factors for recurrence, while tumours around the shoulder girdle and painful lesions were at risk of progression in the observational group. Conclusion Local recurrence rate after surgery was similar to progression rates under observation. Hence, observation in DTF seems to be justified, considering surgery in case of dimensional progression in 2 consecutive controls (3 and 6 months) and in painful lesions, with particular attention to lesions around the shoulder girdle.

Abstract Return to work (RTW) has been specifically identified as a high priority in patients undergoing total hip arthroplasty (THA). This investigation sought to assess the effect of the stem design on patients’ RTW. Secondly, the study aimed to identify risk factors that lead to a delayed RTW. Questionnaires inquiring about RTW, employment history, educational level, type of work, physical demands and joint awareness were administered by post. Further data were collected from patients’ hospital records. 176 patients who underwent THA using a short-stem and 97 patients using a straight-stem design were compared. The median return to work time was 10 weeks [IQR 7–14 weeks], with no significant difference between the two groups (short stems vs. straight stems; 10 [IQR 7–14] vs. 11 [7.5–13.5] weeks; p = 0.693). In the multivariate linear regression analysis, self-employment vs. employee (p = 0.001), dimension of preoperative workload (p = 0.001), preoperative sick leave (p

Objective To assess organization of care in several bone sarcoma centers in Europe affiliated with the European Musculoskeletal Oncology Society (EMSOS) for comparison and to identify potential improvements in organization of care. Methods Data for this observational cross‐sectional study was obtained through healthcare professionals affiliated to EMSOS. The authors formulated 10 questions regarding organization of care. The questions were focused on guidance, multidisciplinary decision‐making, and data storage. A digital questionnaire was synthesized and included quality control. The digital questionnaire was sent to 54 representative members of EMSOS. We did not receive responses from 29 representative countries (53.7%) after one digital invitation and two digital reminders. Results We received data from 25 representatives of bone sarcoma centers from 17 countries across Europe (46.3%). Authorization to perform oncological care in a bone sarcoma center was government issued in 41.2% of cases and based on expertise without governmental influence in 52.9% of cases. In 64.7% of the countries, a national bone tumor guideline regarding for diagnosis and treatment is used in oncological care. A national bone tumor board for extensive case evaluation including classification and advice for treatment is available for 47.1% of the countries. All participating bone sarcoma centers have a mandatory local multidisciplinary meeting before the start of treatment; in 84.0% this meeting takes place once a week. During this multidisciplinary meeting a median of 15 cases (range, 4–40 cases) are discussed. In terms of storage of oncological data, a local registry is used in eight countries (47.1%). A national registry is used in eight countries (47.1%). Conclusions A national bone tumor board gives bone sarcoma centers with little adherence the opportunity to gain knowledge from a more experienced team. Centralization of care in a bone sarcoma center is important to lower incidences. The optimal size for a bone sarcoma center in terms of patient adherence is not known at present.

Background and purpose: Albeit pediatric flexible flat foot (FFF) is a common condition, only a minority of patients become symptomatic. Long-term outcomes of surgically treated pediatric patients with symptomatic FFF are largely unknown. In this systematic review, studies providing outcomes at a mean follow-up of at least 4 years after the procedure in these patients were analyzed. Material and methods: A PubMed search was undertaken involving original articles published up to July 2021 on outcome in children aged 6 to 14 with surgically treated FFF and mean (or minimum) follow-up of at least 4 years. Radiographic and clinical outcomes were analyzed. Results: Of initially 541 entries, 10 could be included in the systematic review (all level IV), involving 846 pediatric patients with 1,536 symptomatic FFF. Pooled mean radiological (n = 8) and clinical follow-up (n = 10) was 5.3 (range 0.5–15) and 7.0 (range 4.1–15) years, respectively. Surgical procedures included arthroereisis (n = 8), lateral column lengthening (n = 1), and Horseman procedure (n = 1). Overall relative frequency of implant-associated complications and wound-healing problems was 3.2% and 1.3%, as well as 2.8% and 1.6% following subtalar arthroereisis only. From preoperative to latest radiological assessment following subtalar arthroereisis (including 3 studies with radiological follow-up < 48 months), pooled median decrease in talonavicular coverage angle (TNCA; –9.2°), anteroposterior talocalcaneal angle (A-TCA; –6.5°), lateral talocalcaneal angle (L-TCA; –3.5°), talar declination angle (TDA; –14°), Moreau Costa Bertani angle (MCB; –13°), and talo-firstmetatarsal angle (L-T1MA; –10°) was observed, as was an increase in calcaneal pitch (4.5°). Interpretation: In symptomatic pediatric FFF patients, surgery is associated with a manageable complication profile, and results in satisfactory long-term clinical as well as radiological outcome. Yet scientific evidence is low, warranting larger scaled studies in the future.

Background: Molecular diagnosis has become an established tool in the characterisation of adult soft-tissue sarcomas (STS). FoundationOne ® Heme analyses somatic gene alterations in sarcomas via DNA and RNA-hotspot sequencing of tumour-associated genes. Methods: We evaluated FoundationOne ® Heme testing in 81 localised STS including 35 translocation-associated and 46 complex-karyotyped cases from a single institution. Results: Although FoundationOne ® Heme achieved broad patient coverage and identified at least five genetic alterations in each sample, the sensitivity for fusion detection was rather low, at 42.4%. Nevertheless, potential targets for STS treatment were detected using the FoundationOne ® Heme assay: complex-karyotyped sarcomas frequently displayed copy-number alterations of common tumour-suppressor genes, particularly deletions in TP53 , NF1 , ATRX , and CDKN2A . A subset of myxofibrosarcomas (MFS) was amplified for HGF ( n = 3) and MET ( n = 1). PIK3CA was mutated in 7/15 cases of myxoid liposarcoma (MLS; 46.7%). Epigenetic regulators (e.g. MLL2 and MLL3 ) were frequently mutated. Conclusions: In summary, FoundationOne ® Heme detected a broad range of genetic alterations and potential therapeutic targets in STS (e.g. HGF/MET in a subset of MFS, or PIK3CA in MLS). The assay’s sensitivity for fusion detection was low in our sample and needs to be re-evaluated in a larger cohort.

Background and purpose — Fibrous dysplasia (FD) is a rare bone disorder associated with pain, deformities, and pathological fractures. The pathophysiological mechanism of FD-related pain remains ill-understood. We evaluated the degree of pain and the potential contributory factors in 2 patient cohorts from Austria and the Netherlands. Patients and methods — 197 patients (16–85 years) with FD (Graz n = 105, Leiden n = 92) completed a survey concerning the presence and severity of pain at their FD site. Sex, age, type of FD, and localization of FD lesions were examined for a relationship with the presence and severity of pain. Results — Of 197 patients from the combined cohort (61% female, mean age 49 (SD 16) years, 76% monostotic) who completed the questionnaires, 91 (46%) reported pain at sites of FD lesions. Severity of pain was higher in patients with lesions of the lower extremities and ribs compared with upper extremity or craniofacial lesions. Severe subtypes of FD (polyostotic/McCune–Albright syndrome) were more often associated with pain, often severe. Interpretation — Our data suggest that almost 50% of patients with FD report pain at FD sites, thus representing a major clinical manifestation of the disorder, importantly also in patients with monostotic lesions. Lesions in lower extremities and ribs were more painful.

Soft tissue sarcomas (STS) are considered non-immunogenic, although distinct entities respond to anti-tumor agents targeting the tumor microenvironment. This study’s aims were to investigate relationships between tumor-infiltrating immune cells and patient/tumor-related factors, and assess their prognostic value for local recurrence (LR), distant metastasis (DM), and overall survival (OS). One-hundred-eighty-eight STS-patients (87 females [46.3%]; median age: 62.5 years) were retrospectively analyzed. Tissue microarrays (in total 1266 cores) were stained with multiplex immunohistochemistry and analyzed with multispectral imaging. Seven cell types were differentiated depending on marker profiles (CD3+, CD3+ CD4+ helper, CD3+ CD8+ cytotoxic, CD3+ CD4+ CD45RO+ helper memory, CD3+ CD8+ CD45RO+ cytotoxic memory T-cells; CD20 + B-cells; CD68+ macrophages). Correlations between phenotype abundance and variables were analyzed. Uni- and multivariate Fine&Gray and Cox-regression models were constructed to investigate prognostic variables. Model calibration was assessed with C-index. IHC-findings were validated with TCGA-SARC gene expression data of genes specific for macrophages, T- and B-cells. B-cell percentage was lower in patients older than 62.5 years (p = .013), whilst macrophage percentage was higher (p = .002). High B-cell (p = .035) and macrophage levels (p = .003) were associated with increased LR-risk in the univariate analysis. In the multivariate setting, high macrophage levels (p = .014) were associated with increased LR-risk, irrespective of margins, age, gender or B-cells. Other immune cells were not associated with outcome events. High macrophage levels were a poor prognostic factor for LR, irrespective of margins, B-cells, gender and age. Thus, anti-tumor, macrophage-targeting agents may be applied more frequently in tumors with enhanced macrophage infiltration.

Background. Follow-up of high-grade bone sarcoma patients with repeated radiological imaging aims at early detection of recurrent disease or distant metastasis. Repeated radiological imaging does expose (mostly young) patients to ionising radiation. At this point, it is not known whether frequent follow-up increases overall survival. Additionally, frequent follow-up subjects patients and families to psychological stress. This study aims to assess follow-up procedures in terms of frequency and type of imaging modalities in bone tumour centres across Europe for comparison and improvement of knowledge as a first step towards a more uniform approach towards bone sarcoma follow-up. Methods. Data were obtained through analysis of several follow-up protocols and a digital questionnaire returned by EMSOS members of bone tumour centres all across Europe. Results. All participating bone tumour centres attained a minimum follow-up period of ten years. National guidelines revealed variations in follow-up intervals and use of repeated imaging with ionising radiation. A local and a chest X-ray were obtained at 47.6% of the responding clinics at every follow-up patient visit. Conclusions. Variations were seen among European bone sarcoma centres with regards to follow-up intervals and use of repeated imaging. The majority of these expert centres follow existing international guidelines and find them sufficient as basis for a follow-up surveillance programme despite lack of evidence. Future research should aim towards evidence-based follow-up with focus on the effects of follow-up strategies on health outcomes, cost-effectiveness, and individualised follow-up algorithms.

Abstract Background Intramuscular / cellular myxomas and low-grade myxofibrosarcomas are two different tumor entities with a significant histological overlap, especially if dealing with small biopsies. Despite the morphological similarities, they differ considerably in their biological behaviour. Intramuscular / cellular myxoma rarely shows signs of recurrence and never metastasizes, in contrast to myxofibrosarcoma that tends to recur more aggressively and to metastasize haematologically. Therefore, it is of great importance to distinguish these lesions - evaluation of GNAS mutation status could be of tremendous help. Methods We reviewed 13 cases with intramuscular / cellular myxomas. The 13 cases included 5 men and 8 women, aged from 33 to 71 years (mean age 55.5 years). Immunohistochemistry was performed as well as next generation sequencing. Ten cases were located in the lower extremities and three cases were located in the upper extremities. Two lesions were initially misdiagnosed as a low-grade myxofibrosarcoma. Results Performing next generation sequencing 12 out of 13 specimens showed a GNAS mutation. Conclusions Our findings demonstrate that GNAS mutations are more common in intramuscular / cellular myxomas, than had been reported in literature in the past. Next generation sequencing for determining GNAS mutation status on small biopsies or diagnostically challenging cases facilitates the diagnosis of intramuscular / cellular myxoma and separates this tumor entity from its mimics.

Abstract Background Fibrous dysplasia of the proximal femur presents with heterogeneous clinical manifestations dictating different surgical approaches. However, to date there are no clear recommendations to guide the choice of surgical approach and no general guidelines for the optimal orthopedic management of these lesions. The objective of this study was to evaluate treatment outcomes of angled blade plates and intramedullary nails, using as outcome indicators revision-free survival, pain, function and femoral neck-shaft-angle. Based on a review of published literature and our study findings, we propose a treatment algorithm, taking into account different factors, which may play a role in the selection of one surgical approach over another. Methods Data were evaluated in thirty-two patients (18 male) from a combined cohort from the Netherlands and Austria, who had a surgical intervention using an angled blade plate (n = 27) or an intramedullary nail (n = 5) between 1985 and 2015, and who had a minimal follow-up of one year. The primary outcome was success of the procedure according to the revised Henderson classification. Secondary outcomes, which were assessed at one year and at the end of follow-up included: function (as measured by walking ability), pain and change in femoral neck-shaft angle over time. Results Analysis of data showed that revision-free survival was 72% after a median follow-up of 4.1 years. Revision was necessary in two patients for structural failure due to a fracture distal to an angled blade plate and in 7 patients due to angled blade plate-induced iliotibial tract pain. At the end of follow-up 91% of all patients had good walking ability and 91% were pain free. There was no significant postoperative change in femoral neck shaft angle. Conclusion Our data show that fibrous dysplasia of the proximal femur can be adequately and safely treated with angled blade plates or intramedullary nails, providing these are used according to specific characteristics of the individual patient. Based on published literature and our own experience, we propose an individualized, patient-tailored approach for the surgical management of fibrous dysplasia of the proximal femur.

Anterior cruciate ligament (ACL) injuries are among the most common knee injuries. The purpose of this study was to compare surgical reconstruction of the ACL between different countries and regions in order to describe differences regarding epidemiological data, reconstruction frequency, and graft choice. A systematic literature search was performed using the ACL study group website in order to identify the relevant knee ligament registers. Four national registries were included, comprising those from Sweden, the UK, New Zealand, and Norway. A large variation was found concerning the total number of primary ACL reconstructions with a reported range from 4.1 to 51.3 per 100,000 inhabitants. The country-specific delay between injury and reconstruction varied between an average of 6.0 months and 17.6 months. The leading sports activities resulting in ACL injury included soccer, alpine skiing, handball, rugby, and netball. Moreover, a strong variability in graft choice for primary reconstruction was found. The comparison of ACL registers revealed large differences, indicating different clinical implications regarding conservative or surgical therapy and choice of the preferable graft. ACL registers offer a real-world clinical perspective with the aim to improve quality and patient safety by investigating factors associated with subsequent surgical outcomes.

Background: Osteoarthritis (OA) as the main chronic joint disease arises from a disturbed balance between anabolic and catabolic processes leading to destructions of articular cartilage of the joints. While mechanical stress can be disastrous for the metabolism of chondrocytes, mechanical stimulation at the physiological level is known to improve cell function. The disease modifying OA drug (DMOAD) diacerein functions as a slowly-acting drug in OA by exhibiting anti-inflammatory, anti-catabolic, and pro-anabolic properties on cartilage. Combining these two treatment options revealed positive effects on OA-chondrocytes. Methods: Cells were grown on flexible silicone membranes and mechanically stimulated by cyclic tensile loading. After seven days in the presence or absence of diacerein, inflammation markers and growth factors were analyzed using quantitative real-time PCR and enzyme linked immune assays. The influence of conditioned medium was tested on cell proliferation and cell migration. Results: Tensile strain and diacerein treatment reduced interleukin-6 (IL-6) expression, whereas cyclooxygenase-2 (COX2) expression was increased only by mechanical stimulation. The basic fibroblast growth factor (bFGF) was down regulated by the combined treatment modalities, whereas prostaglandin E2 (PGE2) synthesis was reduced only under OA conditions. The expression of platelet-derived growth factor (PDGF) and vascular endothelial growth factor A (VEGF-A) was down-regulated by both. Conclusions: From our study we conclude that moderate mechanical stimulation appears beneficial for the fate of the cell and improves the pharmacological effect of diacerein based on cross-talks between different initiated pathways. General significance: Combining two different treatment options broadens the perspective to treat OA and improves chondrocytes metabolism.

Abstract Artificial bone graft substitutes, such as Calcibon, are becoming increasingly interesting as they do not cause donor site morbidity which is an advantage compared to autologous bone grafts. The aim of this study was to evaluate the efficacy and potential complications associated with the use of Calcibon. Twenty-seven patients with benign and low-grade malignant bone tumors were treated with curettage and refilling of the bony cavity. Based on the radiological classification system of Neer, these lesions only comprised Grade I lesions, describing cysts that only require curettage and filling, but no additional treatment. At a mean follow up of six months we observed radiological consolidation without resorption of the bone graft substitute. These observations were also made at a mean follow-up of 13 and 32 months, respectively. According to the classification system of Goslings and Gouma we observed six surgical complications. Summing up, Calcibon seems to be a reliable bone graft substitute with low complication rates. However, delayed resorption should be expected. Calcibon seems to be an alternative to autologous bone grafts or allografts in adequate indications.

Background: Prognostic nomograms for patients with extremity soft tissue sarcoma (eSTS) typically predict survival or the occurrence of local recurrence or distant metastasis at time of surgery. Our aim was to develop and externally validate a dynamic prognostic nomogram for overall survival in eSTS survivors for use during follow-up. Methods: All primary eSTS patients operated with curative intent between 1994 and 2013 at three European and one Canadian sarcoma centers formed the development cohort. Patients with Fédération Française des Centres de Lutte Contre le Cancer (FNCLCC) grade II and grade III eSTS operated between 2000 and 2016 at seven other European reference centers formed the external validation cohort. We used a landmark analysis approach and a multivariable Cox model to create a dynamic nomogram; the prediction window was fixed at five years. A backward procedure based on the Akaike Information Criterion was adopted for variable selection. We tested the nomogram performance in terms of calibration and discrimination. Findings: The development and validation cohorts included 3740 and 893 patients, respectively. The variables selected applying the backward procedure were patient's age, tumor size and its interaction with landmark time, tumor FNCLCC grade and its interaction with landmark time, histology, and both local recurrence and distant metastasis (as first event) indicator variables. The nomogram showed good calibration and discrimination. Harrell C indexes at different landmark times were between 0.776 (0.761–0.790) and 0.845 (0.823–0.862) in the development series and between 0.675 (0.643–0.704) and 0.810 (0.775–0.844) in the validation series. Interpretation: A new dynamic nomogram is available to predict 5-year overall survival at different times during the first three years of follow-up in patients operated for primary eSTS. This nomogram allows physicians to update the individual survival prediction during follow-up on the basis of baseline variables, time elapsed from surgery and first-event history. Keywords: Dynamic prediction, Landmark analysis, Prognostic nomogram, Sarcoma, Soft tissue sarcoma: Survivors

Osteochondromas rarely induce vascular complications by mechanical compression. We present the case of a subclavian artery pseudoaneursym caused by an osteochondroma of the scapula in a 67-year-old male. The diagnosis was based on a previous history of multiple exostoses, computed tomography and magnetic resonance imaging, as well as the local vascular clinical status of the lesion. Surgical treatment consisted of vascular and orthopaedic intervention. First, the vascular surgeon implanted a bypass of the subclavian artery from the ventral aspect, enabling the orthopaedic surgeon to resect the osteochondroma from the dorsal aspect. The patient recovered with full function. Vascular pseundoaneurysms should be taken into consideration in patients with osteochondromas, especially with a known history of multiple hereditary exostoses.

Introduction. Indications discussed for the implantation of expandable prostheses in bone sarcoma patients are unclear. This survey aimed to analyse common practice with this implant type in orthopaedic oncology. Methods. A web-based survey was sent to 98 orthopaedic oncology surgeons. Factors reported in literature to influence the decision on the implantation of a growing prosthesis were covered in individual questions and three case scenarios. Results. The completion rate of the survey was 45% (n = 44). Twenty-seven of 44 surgeons (61%) had implanted between 1 and 15 expandable prostheses within three years. The minimum median patient age was 6.5 years, and 3–5 cm of predicted growth deficit was the minimum before implanting a growing prosthesis. One-third of surgeons do not use growth calculation methods. Two out of three surgeons would rather not implant a growing prosthesis in children with metastatic disease. Conclusions. Our survey confirmed the literature with 3-4 cm as the minimum estimated growth deficit. The minimum age for the implantation of a growing prosthesis is approx. 6.6 years, and therefore the patients are younger than those reported in previous publications. One-quarter of orthopaedic surgeons do not use growing prostheses at all. It remains unclear whether growing prostheses are indicated in patients with metastatic disease.

High grade chondrosarcoma is characterized by its lack of response to conventional cytotoxic chemotherapy, the tendency to develop lung metastases, and low survival rates. Research within the field prioritizes the development and expansion of new treatment options for dealing with unresectable or metastatic diseases. Numerous clinical trials using the proteasome inhibitor bortezomib have shown specific efficacy as an active antitumor agent for treating a variety of solid tumors. However, as of yet the effect of bortezomib on chondrosarcoma has not been investigated. In our study, bortezomib decreased cell viability and proliferation in two different chondrosarcoma cell lines in a time- and dose dependent manner. FACS analysis, mRNA- and protein expression studies illustrated that induction of apoptosis developed through the intrinsic mitochondria-caspase dependent pathway. Furthermore, bortezomib treatment significantly increased expression of the death receptors TRAILR-1 and TRAILR-2 in chondrosarcoma cells. An increased expression of the autophagy markers Atg5/12, Beclin, and LC3BI-II supports the interpretation that bortezomib functions as a trigger for autophagy. Our results demonstrated for the first time that bortezomib reduced viability and proliferation of chondrosarcoma cells, induced apoptosis via the mitochondria-caspase dependent pathway and enhanced death receptor expression and autophagy.

Few studies have been performed to analyze noise levels produced by various surgical instruments in the operating room (OR). The highest levels of noise that have been described were due to instruments used for total knee arthroplasty (TKA). These high levels of noise might be a potential health hazard for patients and medical staff. Therefore, we aimed to measure noise levels of current instruments that are widely used worldwide. During a conventional primary TKA the levels of noise in the OR were measured using a Class 1 integrating-averaging sound level meter. The highest A-weighted equivalent level was produced when using a hammer during the implantation of the femoral and tibial components with 90.2 dBA. In total surgical instruments were used for about 10% of the total time of surgery. Noise exposure due to instrument use during TKA does not seem to be a potential health hazard for medical staff or patients.

Osteoporosis is a systemic disease of the bone that affects millions of people and causes burden for both the affected individual and health systems and societies worldwide. Since the 1970s much research has been done in the field of osteoporosis. The number of citations of a paper reflects its influence and importance to the field. Thomson ISI Web of Science database was searched to retrieve a list of the fifty most cited articles related to osteoporosis and its research. The fifty most cited articles in absolute numbers in the field of osteoporosis were cited from 877 to 3056 times (mean 1141±537). Most papers were published in the basic science category (n=23). 395 authors contributed; a single paper had between one and 62 authors (mean: 10.02±9.9 authors). 12 authors (3.04%) contributed between 7 and 4 papers; 340 authors (86.1%) were at least named once. Corresponding authors were from eight countries with most contributions from the United States (n=34, 68%). The majority of papers were published in the 1990s (n=29). The list of 50 most cited papers presents citation classics in the field of osteoporosis and related research.

Chordomas are rare bone tumors, developed from the notochord and largely resistant to chemotherapy. A special feature of this tumor is the heterogeneity of its cells. By combining high pressure freezing (HPF) with electron tomography we were able to illustrate the connections within the cells, the cell-cell interface, and the mitochondria-associated endoplasmic reticulum membrane complex that appears to play a special role among the characteristics of chordoma. These lipid raft-like regions are responsible for lipid syntheses and for calcium signaling. Compared to other tumor cells, chordoma cells show a close connection of rough endoplasmic reticulum and mitochondria, which may influence the sphingolipid metabolism and calcium release. We quantified levels of ceramide and glycosylceramide species by the methyl tert-butyl ether extraction method and we assessed the intracellular calcium concentration with the ratiometric fluorescent dye Fura-2AM. Measurements of the changes in the intracellular calcium concentration revealed an increase in calcium due to the application of acetylcholine. With regard to lipid synthesis, glucosylceramide levels in the chordoma cell line were significantly higher than those in normal healthy cells. The accumulation of glycosylceramide in drug resistant cancer cells has been confirmed in many types of cancer and may also account for drug resistance in chordoma. This study aimed to provide a deep morphological description of chordoma cells, it demonstrated that HPF analysis is useful in elucidating detailed structural information. Furthermore we demonstrate how an accumulation of glycosylceramide in chordoma provides links to drug resistance and opens up the field for new research options.

Background. The benefit of physical activity for the prevention and treatment of cardiovascular disease (CVD) has been well documented. The aim of the present study was to determine the level of awareness among general practitioners (GPs) of knee and hip problems in patients with CVD or CVD risk. Design. Cross-sectional questionnaire survey. Setting and Subjects. Thirty-five Austrian GPs and 1,118 patients were included. The GPs completed an extraction form about the presence or absence of documented evidence of problems related to the knee and/or hip joint within the patient medical data. Patients, in turn, were asked to complete a questionnaire that included the Oxford Knee/Hip Score and the cardiovascular risk-chart established by the European Society of Cardiology. Results. In 748 patients’ data from medical records and questionnaires were available. 40.9% of these patients suffered from serious knee pain and 32.1% from hip pain. However, in the medical records, in only 51.3% (knee) and 48.1% (hip) of these pain-patients the problems were documented. Conclusion. Joint disorders of the knee and hip problems are considerable barriers to effective physical activity and can therefore contribute to the development of CVD. Our data showed that GP awareness of such knee/hip disorders should be improved.

Anemia refers to low hemoglobin (Hb) levels, represents a common symptom and complication in cancer patients and was reported to negatively influence survival in patients with various malignancies. In the present study, we aimed to explore the prognostic impact of pre-operative Hb levels on clinical outcome in a large cohort of soft tissue sarcoma (STS) patients after curative surgery.Retrospective data from 367 STS patients, which were operated between 1998 and 2013, were included in the study. Cut-off levels for anemia were defined as Hb

Chordomas are rare mesenchymal tumors occurring exclusively in the midline from clivus to sacrum. Early tumor detection is extremely important as these tumors are resistant to chemotherapy and irradiation. Despite continuous research efforts surgical excision remains the main treatment option. Because of the often challenging anatomic location early detection is important to enable complete tumor resection and to reduce the high incidence of local recurrences. The aim of this study was to explore whether DNA methylation, a well known epigenetic marker, may play a role in chordoma development and if hypermethylation of specific CpG islands may serve as potential biomarkers correlated with SNP analyses in chordoma. The study was performed on tumor samples from ten chordoma patients. We found significant genomic instability by Affymetrix 6.0. It was interesting to see that all chordomas showed a loss of 3q26.32 (PIK 3CA) and 3q27.3 (BCL6) thus underlining the potential importance of the PI3K pathway in chordoma development. By using the AITCpG360 methylation assay we elucidated 20 genes which were hyper/hypomethylated compared to normal blood. The most promising candidates were nine hyper/hypomethylated genes C3, XIST, TACSTD2, FMR1, HIC1, RARB, DLEC1, KL, and RASSF1. In summary, we have shown that chordomas are characterized by a significant genomic instability and furthermore we demonstrated a characteristic DNA methylation pattern. These findings add new insights into chordoma development, diagnosis and potential new treatment options.

Reconstruction of the distal radius following tumour resection is challenging and various techniques are recorded. We retrospectively analysed the outcome of five patients (one male and four females) after reconstruction of the distal radius with osteoarticular allograft, following tumour resection. Mean followup was 32 months (range, 4–121). In three of the five patients the dominant limb was affected. Mean bone resection length was 6.5 centimetres (range, 5–11.5). Two grafts developed nonunion, both successfully treated with autologous bone grafting. No infection, graft fracture, or failure occurred. Mean flexion/extension was 38/60 degrees and mean pronation/supination was 77/77 degrees. The mean Mayo wrist score was 84 and the mean DASH score was 8, both representing a good functional result. Therefore we state the notion that osteoarticular allograft reconstruction of distal radius provides good to excellent functional results.

Reconstruction with massive bone allograft and autologous vascularised fibula combines the structural strength of the allograft and the advantages of fibula’s intrinsic blood supply. We retrospectively analysed the outcome of twelve patients (4 male, 8 female) who received reconstruction with massive bone allograft and autologous vascularised fibula after tumour resection in lower limb. Mean age was 17.8 years (range 11–31 years), with following primaries: Ewing’s sarcoma (n=6), osteosarcoma (n=4), liposarcoma grade 2 (n=1), and adamantinoma (n=1). Mean followup was 38.7 months (median 25.7 months; range 2–88 months). Seven tumours were located in the femur and five in the tibia. The mean length of bone defect was 18.7 cm (range 15–25 cm). None of the grafts had to be removed, but there occurred four fractures, four nonunions, and two infections. Two patients developed donor side complication, in form of flexion deformity of the big toe. The event-free survival rate was 51% at two-year followup and 39% at three- and five-year followup. As the complications were manageable, and full weight bearing was achieved in all cases, we consider the combination of massive bone allograft and autologous vascularised fibula a stable and durable reconstruction method of the diaphysis of the lower limbs.

Soft tissue sarcomas (STS) represent a rare group of malignant tumors that frequently exhibit chemotherapeutic resistance and increased metastatic potential. Many studies have demonstrated the great potential of plant-derived agents in the treatment of various malignant entities. The present study investigates the effects of the sesquiterpene lactones costunolide and dehydrocostus lactone on cell cycle, MMP expression, and invasive potential of three human STS cell lines of various origins. Both compounds reduced cell proliferation in a time- and dose-dependent manner. Dehydrocostus lactone significantly inhibited cell proliferation, arrested the cells at the G2/M interface and caused a decrease in the expression of the cyclin-dependent kinase CDK2 and the cyclin-dependent kinase inhibitor p27(Kip1). In addition, accumulation of cells at the G2/M phase transition interface resulted in a significant decrease in cdc2 (CDK1) together with cyclin B1. Costunolide had no effect on the cell cycle. Based on the fact that STS tend to form daughter cell nests and metastasize, the expression levels of matrix metalloproteinases (MMPs), which play a crucial role in extracellular matrix degradation and metastasis, were investigated by Luminex® technology and real-time RT-PCR. In the presence of costunolide, MMP-2 and -9 levels were significantly increased in SW-982 and TE-671 cells. Dehydrocostus lactone treatment significantly reduced MMP-2 and -9 expression in TE-671 cells, but increased MMP-9 level in SW-982 cells. In addition, the invasion potential was significantly reduced after treatment with both sesquiterpene lactones as investigated by the HTS FluoroBlock™ insert system.

In sarcoma surgery besides a wide local resection, limb salvage became more and more important. Reconstruction of bone and soft tissue defects after sarcoma resection poses a major challenge for surgeons. Nowadays a broad range of reconstructive methods exist to deal with bony defects. Among these are prostheses, bone autografts, or bone allografts. Furthermore a variety of plastic reconstructive techniques exist that allow soft tissue reconstruction or coverage after sarcoma resection. Here we discuss the historical highlights, the present role, and possible future options for biological reconstruction.

Introduction. We present the extremely rare case of a patient with three metachronous osteosarcomas within 22 years without evident pulmonary manifestation of disease 30 years after first diagnosis. Case Presentation. In 1983, a high-grade osteosarcoma of the left distal femur was diagnosed in an 18-year-old Caucasian male. He received rotationplasty accompanied by pre- and postoperative chemotherapy. Ten years later, an osteoblastic osteosarcoma occurred in TH12. En bloc resection and pre- and postoperative chemotherapy followed. In 2005, the patient developed another high-grade osteosarcoma in his right distal femur. Treatment included a wide resection and reconstruction with a tumour endoprosthesis as well as (neo)adjuvant chemotherapy. After the third tumour occurrence, cytogenetic and molecular genetic examinations (p53, rb1) were performed, showing a normal genetic pattern. Screening for metastases never showed clinical evidence of extraskeletal tumour manifestation. Discussion. In patients presenting metachronous osteosarcoma, identification of their lesions clonality (second primary tumour or metastases) could lead to a better understanding of tumour development and help to filter patients who need extended long-term followup due to a higher risk of late occurring sarcoma recurrence.