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Over the last decade, demand has increased for developing new, alternative materials in pediatric trauma care to overcome the disadvantages associated with conventional implant materials. Magnesium (Mg)-based alloys seem to adequately fulfill the vision of a homogeneously resorbable, biocompatible, load-bearing and functionally supportive implant. The aim of the present study is to introduce the high-strength, lean alloy Mg‒0.45Zn‒0.45Ca, in wt% (ZX00), and for the first time investigate the clinical applicability of screw osteosynthesis using this alloy that contains no rare-earth elements. The alloy was applied in a growing sheep model with osteotomized bone (simulating a fracture) and compared to a non-osteotomy control group regarding degradation behavior and fracture healing. The alloy exhibits an ultimate tensile strength of 285.7 ± 3.1 MPa, an elongation at fracture of 18.2 ± 2.1%, and a reduced in vitro degradation rate compared to alloys containing higher amounts of Zn. In vivo, no significant difference between the osteotomized bone and the control group was found regarding the change in screw volume over implantation time. Therefore, it can be concluded that the fracture healing process, including its effects on the surrounding area, has no significant influence on degradation behavior. There was also no negative influence from hydrogen-gas formation on fracture healing. Despite the proximal and distal screws showing chronologically different gas release, the osteotomy showed complete consolidation. Statement of Significance Conventional implants involve several disadvantages in pediatric trauma care. Magnesium-based alloys seem to overcome these issues as discussed in the recent literature. This study evaluates the clinical applicability of high-strength lean Mg‒0.45Zn‒0.45Ca (ZX00) screws in a growing-sheep model. Two groups, one including a simulated fracture and one group without fracture, underwent implantation of the alloy and were compared to each other. No significant difference regarding screw volume was observed between the groups. There was no negative influence of hydrogen-gas formation on fracture healing and a complete fracture consolidation was found after 12 weeks for all animals investigated., Acta Biomaterialia, 113, ISSN:1742-7061, ISSN:1878-7568

BACKGROUND: Osteofibrous dysplasia-like adamantinoma (OFD-AD) and classic adamantinoma (AD) are rare, neoplastic diseases with only limited data supporting current treatment protocols. We believe that our retrospective multicenter cohort study is the largest analysis of patients with adamantinoma to date. The primary purpose of this study was to describe the disease characteristics and evaluate the oncological outcomes. The secondary purpose was to identify risk factors for local recurrence after surgical treatment and propose treatment guidelines. METHODS: Three hundred and eighteen confirmed cases of OFD-AD and AD for which primary treatment was carried out between 1985 and 2015 were submitted by 22 tertiary bone tumor centers. Proposed clinical risk factors for local recurrence such as size, type, and margins were analyzed using univariable and multivariate Cox regression analysis. RESULTS: Of the 318 cases, 128 were OFD-AD and 190 were AD. The mean age at diagnosis was 17 years (median, 14.5 years) for OFD-AD and 32 years (median, 28 years) for AD; 53% of the patients were female. The mean tumor size in the OFD-AD and AD groups combined was 7.8 cm, measured histologically. Sixteen percent of the patients sustained a pathological fracture prior to treatment. Local recurrence was recorded in 22% of the OFD-AD cases and 24% of the AD cases. None of the recurrences in the OFD-AD group progressed to AD. Metastatic disease was found in 18% of the AD cases and fatal disease, in 11% of the AD cases. No metastatic or fatal disease was reported in the OFD-AD group. Multivariate Cox regression analysis demonstrated that uncontaminated resection margins (hazard ratio [HR] = 0.164, 95% confidence interval [CI] = 0.092 to 0.290, p < 0.001), pathological fracture (HR = 1.968, 95% CI = 1.076 to 3.600, p = 0.028), and sex (female versus male: HR = 0.535, 95% CI = 0.300 to 0.952, p = 0.033) impacted the risk of local recurrence. CONCLUSIONS: OFD-AD and AD are parts of a disease spectrum but should be regarded as different entities. Our results support reclassification of OFD-AD into the intermediate locally aggressive category, based on the local recurrence rate of 22% and absence of metastases. In our study, metastatic disease was restricted to the AD group (an 18% rate). We advocate wide resection with uncontaminated margins including bone and involved periosteum for both OFD-AD and AD. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Fusions involving NTRK1, NTRK2, and NTRK3 are oncogenic drivers occurring in a spectrum of mesenchymal neoplasms ranging from benign to highly malignant tumors. To gain further insights into the staining profile with the pan-TRK assay, we analyzed a large number of soft tissue sarcomas and correlated our findings with molecular testing. Additionally, we expand the spectrum of NTRK-fusion tumors by reporting a mesenchymal lesion in the lung as well as a mesenchymal skin lesion in the spectrum of benign fibrous histiocytoma with NTRK—fusion. We retrospectively reviewed soft tissue sarcomas diagnosed at the Diagnostic and Research Institute of Pathology, Medical University of Graz, between 1999 and 2019, and cases from the consultation files of one of the authors (BLA). In total, 494 cases were analyzed immunohistochemically with pan-TRK antibody (clone EPR17341, RTU, Roche/Ventana) and positive cases (defined as any cytoplasmic/nuclear staining in more than 1% of tumor cells) underwent next-generation sequencing (NGS). Immunohistochemical staining was observed in 16 (3.2%) cases. Eleven cases with focal weak and moderate cytoplasmic/membranous or focal moderate to strong nuclear staining did not harbor an NTRK-fusion (three synovial sarcomas, three leiomyosarcomas, two extraskeletal myxoid chondrosarcomas, and one each: dedifferentiated liposarcoma, pleomorphic liposarcoma, and myxofibrosarcoma). Four cases showed strong diffuse nuclear and/or cytoplasmatic staining, and one case showed diffuse, but weak cytoplasmic staining. All these cases demonstrated an NTRK-fusion (LMNA-NTRK1, IRF2BP2-NTRK1, TMB3-NTRK1, ETV6-NTRK3, RBPMS-NTRK3). Pan-TRK assay (clone EPR17341, RTU, Roche, Ventana) immunohistochemistry serves as a reliable diagnostic marker that can also be expressed in non-NTRK-rearranged mesenchymal neoplasms. It can be used as a surrogate marker for identification of NTRK fusion, nevertheless, an RNA-based NGS for detection of the specific fusion should be performed to confirm the rearrangement, if patients are undergoing targeted therapy. Additionally, we identified NTRK-fusion-positive, primary mesenchymal tumors of the lung and the skin.

Purpose In many cases, the diagnosis of a periprosthetic joint infection (PJI) consisting of the clinical appearance, laboratory tests, and other diagnostic tools remains a difficult task. Single serum biomarkers are easy to collect, are suitable for periodical assessment, and are a crucial tool in PJI diagnosis, but limited sensitivity or specificity is reported in literature. The aim of this study was to combine the best-performing single serum biomarkers into a multi-biomarker model aiming to improve the diagnostic properties. Methods Within a 27-month period, 124 surgical procedures (aseptic or septic revision total knee arthroplasty (TKA) or total hip arthroplasty (THA)) were prospectively included. The serum leukocyte count, C-reactive protein (CRP), interleukin-6, procalcitonin, interferon alpha, and fibrinogen were assessed 1 day prior to surgery. Logistic regression with lasso-regularization was used for the biomarkers and all their ratios. After randomly splitting the data into a training (75%) and a test set (25%), the multi-biomarker model was calculated and validated in a cross-validation approach. Results CRP (AUC 0.91, specificity 0.67, sensitivity 0.90, p value 0.03) and fibrinogen (AUC 0.93, specificity 0.73, sensitivity 0.94, p value 0.02) had the best single-biomarker performances. The multi-biomarker model including fibrinogen, CRP, the ratio of fibrinogen to CRP, and the ratio of serum thrombocytes to CRP showed a similar performance (AUC 0.95, specificity 0.91, sensitivity 0.72, p value 0.01). Conclusion In this study, multiple biomarkers were tested for their diagnostic performance, with CRP and fibrinogen showing the best results regarding the AUC, accuracy, sensitivity, and specificity. It was not possible to further increase the diagnostic accuracy by combining multiple biomarkers using sophisticated statistical methods.

Introduction Traumatic brain injury (TBI) remains a leading cause of hospital admission and mortality, intracranial hemorrhage (ICH) presents a severe complication. Low complication tolerance in developed countries and risk uncertainty, often cause excessive observation, diagnostics and hospitalization, considered unnecessary and expensive. Risk factors predicting ICH, progression and death in patients hospitalized with mild TBI have not been identified yet. Methods Mild TBI cases indicated for cranial computer tomography (CT) and hospitalization, according to international guidelines, at our Level I Trauma Center between 2008 and 2018 were retrospectively included. Multivariate logistic regression was performed for ICH, progression and mortality predictors. Results 1788 mild TBI adults (female: 44.3%; age at trauma: 58.0 ± 22.7), were included. Skull fracture was diagnosed in 13.8%, ICH in 46.9%, ICH progression in 10.6%. In patients p = 0.004) and skull fracture (p p p 65 years, age (p = 0.009), anticoagulation (p = 0.007) and neurocranial fracture (p p = 0.01) was a risk factor for mortality following ICH in mild TBI. Late-onset ICH only occurred in mild TBI cases with at least two of these risk factors: age > 65, anticoagulation, neurocranial fracture. Overall hospitalization could have been reduced by 15.8% via newly identified low-risk cases. Conclusions Age, skull fracture and chronic alcohol abuse require vigilant observation. Repeated CT in initially ICH negative cases should only be considered in newly identified high-risk patients. Non-ICH cases aged

Summary Background First tarsometatarsal joint (TMT-1) hypermobility might cause hallux valgus deformity (HV), and recurrence following surgical correction. Anatomic findings, indicating tibialis anterior tendon (TAT) involvement in TMT‑1 stabilization, led to the development of cross-glide test allowing clinical TMT‑1 stability testing. Cross-glide test function was evaluated in anatomical specimens and in the clinical setting, compared to simulated weight-bearing computer tomography (CT) analysis. Methods Cross-glide test was evaluated in 6 healthy lower leg specimens before and after TAT transection. Clinical testing was performed prospectively in 36 feet (6 controls, 21 HV, 9 recurrent HV); consecutive weight-bearing CT analysis was performed. Results from clinical testing were compared to CT analysis. Results TMT‑1 instability significantly increased in anatomic specimens following TAT transection (p = 0.009). In the clinical setting, all healthy feet were cross-glide test negative, 62% of HV cases and all recurrent HV feet were positive. In the CT analysis- Compared to controls the HV cases revealed significantly increased MT‑1 internal rotation (p = 0.003) and decreased dorsal angle (p = 0.002), considered as collapsing forefoot signs; HV recurrent cases revealed similar results. Positive cross-glide tested cases revealed increased MT‑1 internal rotation values (p p p = 0.043) in CT analysis, and HV and IMT (intermetatarsal) angle were significantly higher (p = 0.005, p = 0.006). 15 HV recurrence cases, treated with TMT‑1 arthrodesis, revealed no recurrence during follow-up. Conclusion Cross-glide test allows reliable clinical TMT‑1 instability testing, via TAT tension, and is less laborious than CT analysis. We recommend TMT‑1 arthrodesis in cases with instability in clinical testing, to avoid HV recurrence.

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.

IntroductionAnatomic cruciate ligament reconstruction is known to be correlated with better clinical results. The aim of the study was to provide a simple method to enable anatomic results in the setting of PCL reconstruction. We, therefore, assessed the tibial and femoral insertion site of the posterior cruciate ligament (PCL) by the use of an objective coordinate system in an anatomical study. We also sought to show reproducibility of these measurements using intra- and inter-observer coefficients.Materials and methodsWe studied 64 knees, previously preserved according to Thiel’s technique. After proper preparation of the articular surfaces of both the tibiae and femora, photographs were taken according to a standardized protocol. PCL footprints were measured by the use of a coordinate system twice by two examiners. We evaluated these measurements by use of the Cohen’s kappa inter- and intra-observer coefficient for two observers.ResultsTibial and femoral measurements of PCL footprints were generated with highly comparable inter- (k = 0.970) and intra-observer (k = 0.992) coefficients and may, therefore, be considered as highly reproducible.ConclusionOur findings confirmed the reproducibility of defining PCL footprints using a coordinate system and may contribute to planning intraoperative graft-placement to ensure optimal conditions in the upcoming techniques for PCL reconstruction.

Background The aim of the current study was to evaluate the impact of the coronavirus disease (COVID-19) pandemic on musculoskeletal tumor service by conducting an online survey of physicians. Methods The survey was conducted among the members of the ISOLS (International Society of Limb Salvage) and the EMSOS (European Musculo-Skeletal Oncology Society). The survey consisted of 20 questions (single, multiple-response, ranked): origin and surgical experience of the participant (four questions), potential disruption of healthcare (12 questions), and influence of the COVID-19 pandemic on the particular physician (four questions). A matrix with four different response options was created for the particular surgical procedures). Results One hundred forty-nine physicians from five continents completed the survey. Of the respondents, 20.1% and 20.7% stated that surgery for life-threatening sarcomas were stopped or delayed, respectively. Even when the malignancy was expected to involve infiltration of a neurovascular bundle or fracture of a bone, still 13.8% and 14.7% of the respondents, respectively, stated that surgery was not performed. In cases of pending fractures of bone tumors, 37.5 to 46.2% of operations were canceled. Conclusion The SARS-CoV-2 pandemic caused a significant reduction in healthcare (surgery, radiotherapy, chemotherapy) for malignancies of the musculoskeletal system. Delaying or stopping these treatments is life-threatening or can cause severe morbidity, pain, and loss of function. Although the coronavirus disease causes severe medical complications, serious collateral damage including death due to delayed or untreated sarcomas should be avoided.

Summary The results of this study show increased formation of bone in the subchondral areas in advanced stages of osteoarthritis of the knee. These changes seem to be influenced by mechanical factors. Introduction Subchondral bone changes seem to contribute to the progression of knee osteoarthritis (OA). This study aimed to analyze subchondral bone microstructure in specimens of late-stage knee OA in respect to articular cartilage damage, meniscus integrity, and knee joint alignment. Methods Thirty proximal tibiae of 30 patients (20 female and 10 male) with late-stage OA retrieved during total knee arthroplasty were scanned using a high-resolution micro-computed tomography. The scans were semi-automatically segmented into five volumes of interest. The volumes of interest were then further analyzed using commercially available software. The degree of articular cartilage damage was assessed semi-quantitatively by magnetic resonance imaging before surgery. Results The mean bone fraction volume (bone volume/total volume (BV/TV)) in all weight-bearing locations was significantly higher compared to the non-weight-bearing reference point below the anterior cruciate ligament (p = 0.000). The mean BV/TV in the medial compartment was significantly higher compared to the lateral compartment (p = 0.007). As for the BV/TV in intact menisci, there was a significantly lower subchondral bone fraction volume compared to subluxated or luxated menisci in the medial (p = 0.020) and lateral compartment (p = 0.005). Varus alignment had a significantly higher subchondral BV/TV in the medial compartment, whereas valgus alignment had a significantly higher subchondral BV/TV in the lateral compartment (p = 0.011). Conclusions The results show significant differences of subchondral bone microstructural parameters in respect to cartilage damage, meniscus’ structural integrity, and knee joint alignment. Therefore, subchondral bone changes seem to be a secondary process in the late-stage OA of the knee caused by mechanical changes.

ZusammenfassungChordome sind maligne Knochentumoren, die mit einer jährlichen Inzidenz von 0,08 pro 100.000 Personen auftreten. Sie zeigen eine notochordale Differenzierung mit einer nukleären Expression von Brachyury (TBXT). Hauptlokalisation ist das axiale Skelett vom Clivus bis zum Sakrum und dem Os coccygis. Chordome wachsen langsam und lange nur lokal destruierend. Sie werden daher oft erst spät diagnostiziert. Putative Vorläuferläsionen sind Chordareste und der benigne notochordale Zelltumor. Dabei handelt es sich um zumeist mikroskopisch kleine, intraossäre Läsionen. Bei Chordomen werden unterschiedliche histologische Subtypen differenziert, welche sich prognostisch unterscheiden. Wiederkehrende genetische Veränderungen als Tumorauslöser sind nicht bekannt. Brachyury scheint eine noch nicht im Detail geklärte Schlüsselfunktion in der Entstehung von Chordomen zu besitzen. Die chirurgische En-bloc-Resektion mit negativen Resektionsrändern ist die einzige kurative Behandlungsoption. Die Hochdosisbestrahlung, speziell mit Protonen und Carbonionen, ist eine therapeutische Alternative in inoperablen Fällen. Medikamentöse Therapien sind für Chordome derzeit nicht zugelassen. Erste klinische Studien zu neuen Therapiemodalitäten laufen.

Background Despite the fact that about one third of patients with primary localized extremity soft tissue sarcoma (eSTS) will develop metastatic disease, abdominal metastases (AM) and retroperitoneal metastases (RM) constitute rare events. There is no clear consensus on how to achieve follow-up on patients with primary localized eSTS following curative resection, especially regarding the surveillance of potential AM/RM. Aim To systematically analyse incidence, diagnosis, treatment and outcome of AM/RM in eSTS patients. Methods In this systematic review, 899 studies available in PubMed and published between 2000 and 2018 were screened, identifying 17 original articles focused on AM or RM in eSTS. Article selection was based on the PRISMA guidelines, using the search terms (abdominal metastasis AND soft tissue sarcoma) and (soft tissue sarcoma metastasis abdomen). All studies published between January 1, 2000 and December 31, 2018 were screened. Further articles were identified by cross-searching article references, with the final search date being February 18, 2019. Due to limited data and the different reporting techniques used, the present review focused on descriptive analysis of the included studies. Results Of the 17 studies included, six original articles reported on incidence ± diagnosis, therapy and outcome in AM and RM, whilst three original and eight case reports focused on diagnostic pathway, therapeutic procedures or outcomes without allowing conclusions regarding incidence of AM and RM. According to the former six studies, incidence of AM ranged from 0.9%-5.6% in patients with miscellaneous histological subtypes, and up to 12.1% in patients with myxoid liposarcoma. The most common histological subtypes that developed AM or RM were (myxoid) liposarcoma and leiomyosarcoma, but also rare subtypes such as epithelioid sarcoma, myxofibrosarcoma, synovial sarcoma, and malignant peripheral nerve sheath tumour had been reported to develop AM/RM. Surgery for AM/RM was performed in five of eight case-reports (62.5%) and in 20.8%-100.0% of original articles. In particular, patients with hepatic metastases undergoing metastasectomy had a survival benefit compared to patients treated with chemotherapy or best supportive care (> 3 years vs Conclusion Patients with eSTS should undergo surveillance with abdominal ultrasonography/computed tomography, or even whole-body-magnetic resonance imaging to detect AM/RM at an early stage.

Background. Nodular fasciitis (NF) is a self-limiting, benign mesenchymal neoplasm of fibroblastic/myofibroblastic origin. Due to the fast growth, cellularity, and frequently observed high mitotic count, it is commonly misdiagnosed as a sarcoma, often resulting in overtreatment. Intraarticular examples of NF are extremely rare. Radiologically, NF can mimic fibroma of the tendon sheath, tenosynovial giant cell tumor, and synovial chondromatosis. Histology can vary from hypercellular, mitotically active lesions to fibrotic, less cellular ones, and can, therefore, mimic other benign and low-grade malignant neoplasms. Recently, the MYH9-USP6 fusion has been found in up to 92% of NF. Case Presentation. In this article, we report a case of a 38-year-old patient with an intraarticular lesion, radiologically suspicious of tenosynovial giant cell tumor. Histology demonstrated a spindle cell lesion composed of fibroblasts/myofibroblasts embedded in a highly collagenous/hyalinized stroma, partly arranged in short fascicles. Extravasated erythrocytes and rare mitotic figures were present. Immunohistochemically, tumor cells expressed smooth muscle actin and were negative for desmin, β-catenin, CD34, and SOX10. These findings rendered the diagnosis of NF. Molecular analysis using next-generation sequencing (Archer FusionPlex Sarcoma Panel) revealed gene rearrangement involving USP6 and MYH9 supporting the diagnosis of NF in the knee joint. Conclusions. Radiological and histological features of NF can overlap with other benign and low-grade malignant lesion. Identification of the USP6 gene rearrangements or finding of the MYH9-USP6 fusion, especially in core needle biopsies and in the lesions occurring at unusual sites, can result in adequate therapeutic approach avoiding overtreatment.

Purpose Our aim was to assess the outcome with respect to cumulative revision rates of unicompartmental knee arthroplasty (UKA) by comparing published literature and arthroplasty registry data. Our hypothesis was that there is a superior outcome of UKA described in dependent clinical studies compared to independent studies or arthroplasty registers. Methods A systematic review of all clinical studies on UKA in the past decade was conducted with the main endpoint revision rate. Revision rate was calculated as “revision per 100 component years (CY)”. The respective data were analysed with regard to a potential difference of the percentage of performed revision surgeries as described in dependent and independent clinical studies. Clinical data were further compared to arthroplasty registers in a systematic search algorithm. Results In total, 48 study cohorts fulfilled our inclusion criteria and revealed 1.11 revisions per 100 CY. This corresponds to a revision rate of 11.1% after 10 years. No deviations with regard to revision rates for UKA among dependent and independent clinical literature were detected. Data from four arthroplasty registers showed lower survival rates after 10 years compared to published literature without being significant. Conclusions The outcomes of UKA in dependent and independent clinical studies do not differ significantly and are in line with arthroplasty register datasets. We cannot confirm biased results and the authors recommend the use of UKAs in properly selected patients by experts in their field.

Background The aim of this series was to investigate the efficiency of an intraoperative cell salvage system (ICS) removing metal ions during revision of metal-on-metal (MoM) devices to proof the possibility of re-transfusion of the collected blood. Materials and methods Between 2014 and 2018, five consecutive patients underwent revision surgery of their MoM total hip arthroplasty due to wear of the polyethylene-metal sandwich inlay or local massive metallosis with aseptic loosing of the cup. Aspiration of joint fluid of all hip prostheses was done and blood was taken to measure the metal ion concentrations, preoperatively. Perioperatively, blood was collected using an ICS before and after filtration and analyzed for Co and Cr concentrations. At that time, there was no re-transfusion of the collected and filtrated blood due to unknown metal ion concentrations. Results The mean preoperative serum Co and Cr concentrations in the blood were 31.28 μg/L (range 0.22–77.47) and 17.33 μg/L (range 0.59–51.31), whereas the mean local concentrations in the aspiration fluid were 728-fold and 822-fold higher. The Co and Cr concentrations measured in the collected blood before filtration were 70.61 μg/L (range 9.40–173.00) and 337.21 μg/L (range 8.76–1383.0) and decreased markedly to average concentrations of 15.49 μg/L and 41.88 μg/L, respectively. These differences were statistically not significant (Co: p = 0.117, Cr: p = 0.175), although the mean reduction rates were 78% and 88% for Co and Cr, respectively. Conclusion The current series showed that in case of revision of MoM hip devices, metal ions are still contained in the collected blood following filtration using a modern high-level ICS. Therefore, we would only recommend blood re-transfusion in case of low preoperative Co and Cr concentrations and sufficient renal function to warrant patients’ safety.

PurposeMetaphyseal fixation in revision total knee arthroplasty (RTKA) is a very promising treatment option for extended bone defects. Currently published mid-term results remain limited. The purpose was to analyse the implant durability, the clinical and the radiological mid-term results in RTKA when using metaphyseal sleeves.MethodsClinical and radiological follow-up examinations were performed in 92 patients (93 knees) with RTKA using hybrid fixation technique (cementless sleeves and stem). Radiographic measurements regarding osseointegration at the bone–sleeve interface were performed and the range of motion (ROM), a subjective satisfaction score (SSS), the American Knee Society Score (KSS), the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) as well as the SF-36 Health survey were examined. Bone defects were analysed using the Anderson Orthopaedic Research Institute (AORI) classification.ResultsNo knee had to be revised due to aseptic loosening at the time of the follow-up (mean 6.3 years ± 2.3, minimum 2 years). Satisfactory radiographic osseointegration at the sleeve/bone interface was detected in 96.1% of cases. 17 knees (18.2%) had to be re-revised, 15 of them due to a recurrent infection and 2 due to aseptic reasons (mediolateral instability and a periprosthetic fracture). The median of the ROM (96°), SSS (8), KSS (87), WOMAC (9), SF-36 MCS (55) and SF-36 PCS (38) showed very satisfying results.ConclusionNo case of aseptic loosening was found in this large series of RTKA with extended bone defects using metaphyseal sleeve fixation. In this large retrospective series, it has been shown that this technique is an excellent treatment option for extended bone defects in RTKA surgery.Level of evidenceRetrospective cohort study, level III.

Osteoarthritis (OA) is the most common joint disorder and is characterized by the degeneration of articular cartilage. To develop new therapeutic approaches, we investigated the effect of shikonin derivatives on inflammation, MMP expression, and the regulation of MAPK signaling in human healthy (HC) and OA chondrocytes (pCH-OA). Viability was analyzed using the CellTiter-Glo® Assay. Inflammatory processes were investigated using a proteome profiler™ assay. Furthermore, we analyzed the effects of the shikonin derivatives by protein expression analysis of the phosphorylation pattern and the corresponding downstream gene regulation using RT-qPCR. Both HC and pCH-OA showed a dose-dependent decrease in viability after treatment. The strongest effects were found for shikonin with IC50 values of 1.2 ± 0.1 µM. Shikonin counteracts the inflammatory response by massively reducing the expression of the pro-inflammatory mediators. The phosphorylation level of ERK changed slightly. pJNK and pp38 showed a significant increase, and the downstream targets c/EBPs and MEF2c may play a role in the cartilage homeostasis. STAT3 phosphorylation decreased significantly and has a chondroprotective function through the regulation of cyclin D1 and Sox9. Our results demonstrate for the first time that shikonin derivatives have extensive effects on the inflammatory processes, MAPKs, and IL6/STAT3 downstream regulation in healthy and OA chondrocytes.

Objective Despite massive efforts, there are no diagnostic blood biomarkers for knee osteoarthritis (KOA). This study investigated several candidate diagnostic biomarkers and the metabolic phenotype in end-stage KOA in the context of obesity. Design In this cross-sectional study, adult patients undergoing knee arthroplasty were enrolled and KOA severity was assessed using the Lequesne index. Blood biomarkers with an important role in obesity, the metabolic syndrome, or KOA (oxidized form of low-density lipoprotein [oxLDL], advanced glycation end product [AGE], soluble AGE receptor [sRAGE], fatty acid binding protein 4 [FABP4], phospholipase A2 group IIA [PLA2G2A], fibroblast growth factor 23 [FGF-23], ghrelin, leptin, and resistin) were measured using enzyme-linked immunosorbent assay (ELISA; n = 70) or Luminex technique (subgroup of n = 35). H1-NMR spectroscopy was used for the quantification of metabolite levels (subgroup of n = 31). The hip-knee-ankle angle was assessed. Multivariable and multivariate regression analysis was used to examine the relationship of biomarkers with body mass index (BMI) and KOA severity in complete case and multiple imputation analysis. Results While most of the investigated biomarkers were not associated with KOA severity, FABP4 and leptin were found to correlate with BMI and gender. Resistin was associated with Lequesne index in complete case analysis. Using a targeted metabolomics approach, BMI-dependent changes in the metabolome were hardly visible. Conclusions Our findings confirm studies on FABP4, leptin, and resistin with regard to obesity and the metabolic syndrome. There was no association of the investigated biomarkers with KOA severity, most likely due to the patient selection (end-stage KOA patients). Based on this absence of BMI-dependent changes in the metabolome, we might assume that BMI is not correlated with KOA severity in this specific patient group.

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.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.Perioperatively, 75 patients (17.4%) had received lrRBCTs. Older patients, deep, large, lower limb STS rather required lrRBCTs (all p 0.05). No significant association between lrRBCT administration and LR- (p = 0.582) or DM-risk (p = 0.084) was observed. LrRBCT was associated with worse OS in univariate analysis (HR: 2.222; p 0.001), with statistical significance lost upon multivariate analysis (HR: 1.658; p = 0.059; including age, histology, size, grading, amputation, depth). Adding preoperative haemoglobin in subgroup of 220 patients with laboratory parameters revealed significant negative impact of low haemoglobin on OS (p = 0.014), whilst effect of lrRBCT was further diminished (p = 0.167).Unfavourable prognostic factors prevail in STS patients requiring lrRBCTs. Low haemoglobin levels rather than lrRBCT seem to reduce OS.

This retrospective study aimed at analyzing the impact of metastasectomy on post-metastasis survival (PMS) in bone sarcoma patients with lung metastases. Altogether, 47 bone sarcoma patients (24 males, median age at diagnosis of lung metastases: 21.8 (IQR: 15.6–47.3) years) with primary (n = 8) or secondary (n = 39) lung metastases treated at a single university hospital were retrospectively included. Based on a propensity score, inverse probability of treatment weight (IPTW) was calculated to account for selection bias whether patients had undergone metastasectomy or not. The most common underlying histology was osteosarcoma (n = 37; 78.7%). Metastasectomy was performed in 39 patients (83.0%). Younger patients (p = 0.025) with singular (p = 0.043) and unilateral lesions (p = 0.024), as well as those with an interval ≥ 9 months from primary diagnosis to development of lung metastases (p = 0.024) were more likely to undergo metastasectomy. Weighted 1- and 3-year PMS after metastasectomy was 80.8% and 58.3%, compared to 88.5% and 9.1% for patients who did not undergo metastasectomy. Naive Cox-regression analysis demonstrated a significantly prolonged PMS for patients with metastasectomy (HR: 0.142; 95%CI: 0.045–0.450; p = 0.001), which was confirmed after IPTW-weighting (HR: 0.279; 95%CI: 0.118–0.662; p = 0.004), irrespective of age, time to metastasis, and the number of lesions. In conclusion, metastasectomy should be considered in bone sarcoma patients with lung metastases, after carefully considering the individual risks, to possibly improve PMS.

To overcome the resistance to radiotherapy in chondrosarcomas, the prevention of efficient DNA repair with an additional treatment was explored for particle beams as well as reference X-ray irradiation. The combined treatment with DNA repair inhibitors—with a focus on ATRi VE-821—and proton or carbon ions irradiation was investigated regarding cell viability, proliferation, cell cycle distribution, MAPK phosphorylation, and the expression of key DNA repair genes in two human chondrosarcoma cell lines. Pre-treatment with the PARPis Olaparib or Veliparib, the ATMi Ku-55933, and the ATRi VE-821 resulted in a dose-dependent reduction in viability, whereas VE-821 has the most efficient response. Quantification of γH2AX phosphorylation and protein expression of the DNA repair pathways showed a reduced regenerative capacity after irradiation. Furthermore, combined treatment with VE-821 and particle irradiation increased MAPK phosphorylation and the expression of apoptosis markers. At the gene expression and at the protein expression/phosphorylation level, we were able to demonstrate the preservation of DNA damage after combined treatment. The present data showed that the combined treatment with ATMi VE-821 increases the radiosensitivity of human chondrosarcoma cells in vitro and significantly suppresses efficient DNA repair mechanisms, thus improving the efficiency of radiotherapy.

Weitere Nicht-UDE Autoren sind nicht mit aufgeführt. enosynovial giant cell tumour (TGCT) is a rare, locally aggressive, mesenchymal tumor arising from the joints, bursa and tendon sheaths. TGCT comprises a nodular- and a diffuse-type, with the former exhibiting mostly indolent course and the latter a locally aggressive behavior. Although usually not life-threatening, TGCT may cause chronic pain and adversely impact function and quality of life (QoL). CSFR1 inhibitors are effective with benefit on symptoms and QoL but are not available in most countries. The degree of uncertainty in selecting the most appropriate therapy and the lack of guidelines on the clinical management of TGCT make the adoption of new treatments inconsistent across the world, with suboptimal outcomes for patients. A global consensus meeting was organized in June 2022, involving experts from several disciplines and patient representatives from SPAGN to define the best evidence-based practice for the optimal approach to TGCT and generate the recommendations presented herein.

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.

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 p = 0.252); HHS (p = 0.798)]. Radiographic assessment of LLD following THA may not be performed early postoperatively, as measurements appear to inaccurately reflect actual LLDs at this time, potentially due incomplete leg extension and/or inhibited weight-bearing.

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.

Fragestellung: Die Implantation einer Hüfttotalendoprothese etablierte sich als eine der Operationen des letzten Jahrhunderts in der Orthopädie & Traumatologie. Lebensqualität und Funktion sind nicht nur Schlagwörter, sondern Umstände welche ein zufriedenstellendes und [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Fragestellung: Implantation von Kurzschaftprothesen gewinnt seit ein paar Jahren zunehmend an Popularität. Im Zuge dessen wurde 2015 das Kurzschaftsystem ANA.NOVA® Alpha Schaft Proxy® am Markt eingeführt. Um die Performance dieses System beurteilen zu können, wurde eine prospektive [zum vollständigen Text gelangen Sie über die oben angegebene URL]

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.

Background: The updated 8th version of the AJCC-staging system for soft tissue sarcomas (STS) has been criticised for omitting tumour depth as category-defining variable and eventually not improving prognostic accuracy in comparison to the 7th version. This study aimed at investigating the prognostic accuracy of both AJCC-versions in STS-patients treated at European tertiary sarcoma centres.Methods: 1032 patients (mean age: 60.7 +/- 16.3 years; 46.0% [n = 475] females; median follow-up: 38.6 months), treated at five tertiary sarcoma centres for localised, intermediate or high-grade STS of extremities and trunk were retrospectively included. Uni- and multivariate Cox-regression models and Harrell's C-indices were calculated to analyse prognostic factors for overall survival (OS) and assess prognostic accuracy.Results: In univariate analysis, prognostic accuracy for OS was comparable for both AJCC-versions (C-index: 0.620 [8th] vs. 0.614 [7th]). By adding margins, age, gender, and histology to the multivariate models, prognostic accuracy of both versions could be likewise improved (C-index: 0.714 [8th] vs. 0.705 [7th]). Moreover, tumour depth did not significantly contribute to prognostic accuracy of the 8th version's multivariate model (C-index for both models: 0.714). Stratification into four main T-stages based on tumour size only, as implemented in the 8th version, significantly improved prognostic accuracy between each category. However, T-stages as defined in the 7th version had poorer discriminatory power (C-index: 0.625 [8th] vs. 0.582 [7th]).Conclusion: Both AJCC-versions perform equally well regarding prognostic accuracy. Yet, simplification of the 8th version by omitting tumour depth as T-stage-defining parameter, whilst emphasizing the importance of tumour size, should be considered advantageous. (C) 2021 Elsevier Ltd, BASO similar to The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Background There is no single blood biomarker for the staging of knee osteoarthritis (KOA). The purpose of this study was to assess the relationship of obesity, serum biomarkers, the hip-knee-ankle angle (HKAA) with sonographic cartilage thickness. Methods We conducted a cross-sectional study of n = 33 patients undergoing knee arthroplasty. Body mass index (BMI) was recorded, and patients were grouped based on BMI. Serum blood samples were collected, and the following biomarkers were measured using the ELISA technique (subgroup of n = 23): oxidized low-density lipoprotein (oxLDL), soluble receptor for advanced glycation end-products (sRAGE), fatty acid–binding protein 4 (FABP4), membrane-bound phospholipase A2 (PLA2G2A). The HKAA was analyzed on full-length limb standing x-ray images. Cartilage thickness was assessed on ultrasound images. Multivariable regression analysis was performed to account for confounding. Results After adjusting for age, gender, and HKAA, obese patients had thicker medial femoral cartilage (β = 0.165, P = 0.041). Furthermore, lateral cartilage thickness was negatively correlated with FABP4 level after adjusting for of age, gender, BMI, and HKAA (β = −0.006, P = 0.001). Confirming previous studies, after adjustment, FABP4 level was associated with a higher BMI group (β = 42.99, P < 0.001). None of the other markers (oxLDL, PLA2G2A, and sRAGE) was associated with BMI or cartilage thickness. Discussion Our results indicate that BMI has a weak, positive association with cartilage thickness in end-stage KOA patients. FABP4 levels were negatively associated with cartilage thickness. While our study is limited by a small sample size, these results further highlight the role of FABP4 as promising biomarkers of burden of disease in KOA.

Background Tenosynovial Giant-Cell Tumour (TGCT) is a benign clonal neoplastic proliferation arising from the synovium, causing a variety of symptoms and often requiring repetitive surgery. This study aims to define the economic burden—from a societal perspective—associated with TGCT patients and their health-related quality of life (HRQOL) in six European countries. Methods This article analyses data from a multinational, multicentre, prospective observational registry, the TGCT Observational Platform Project (TOPP), involving hospitals and tertiary sarcoma centres from six European countries (Austria, France, Germany, Italy, the Netherlands, and Spain). It includes information on TGCT patients’ health-related quality of life and healthcare and non-healthcare resources used at baseline (the 12-month period prior to the patients entering the registry) and after 12 months of follow-up. Results 146 TGCT patients enrolled for the study, of which 137 fulfilled the inclusion criteria. Their mean age was 44.5 years, and 62% were female. The annual average total costs associated with TGCT were €4866 at baseline and €5160 at the 12-month follow-up visit. The annual average healthcare costs associated with TGCT were €4620 at baseline, of which 67% and 18% corresponded to surgery and medical visits, respectively. At the 12-month follow-up, the mean healthcare costs amounted to €5094, with surgery representing 70% of total costs. Loss of productivity represented, on average, 5% of the total cost at baseline and 1.3% at follow-up. The most-affected HRQOL dimensions, measured with the EQ-5D-5L instrument, were pain or discomfort, mobility, and the performance of usual activities, both at baseline and at the follow-up visit. Regarding HRQOL, patients declared a mean index score of 0.75 at baseline and 0.76 at the 12-month follow-up. Conclusion The results suggest that TGCT places a heavy burden on its sufferers, which increases after one year of follow-up, mainly due to the healthcare resources required—in particular, surgical procedures. As a result, this condition has a high economic impact on healthcare budgets, while the HRQOL of TGCT patients substantially deteriorates over time.

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.

PurposeThe purpose of this study was to provide a matched cohort comparison of clinical and functional outcome scores, range of motion and quality of life following unicompartmental knee arthroplasty (UKA) or total knee arthroplasty (TKA). The hypothesis was that patients receiving UKA report better results than comparable patients who receive conventional TKA.MethodsClinical and functional results of 35 patients with medial end-stage osteoarthritis who had received a fixed-bearing UKA were compared with the results of 35 matched patients who had received a TKA from the same manufacturer by the same surgeon. Outcome scores were measured before surgery and at final follow-up using Tegner Activity Scale (TAS), range of motion (ROM) and Short Form 36 Health Survey (SF-36). The Knee Society Score (KSS) was assessed at final follow-up. The mean observation period was 2.3 years in both groups.ResultsThe preoperative knee scores had no statistically significant differences between the two groups. Postoperatively, however, UKAs performed significantly better regarding TAS and ROM (4 vs. 3 and 118.4 vs. 103.7, respectively). The results of the SF-36 showed significantly better results for the UKA group in the mental component summary score and in the subscale of social function.ConclusionsThe present study suggests that UKA is associated with higher activity level, higher quality of life, and greater ROM when compared with TKA on comparable patients. Prolonged clinical follow-up in a larger patient cohort with a randomised-controlled study design would be beneficial to confirm these findings.Level of evidenceIII.

Intraoperative radiography imaging is essential for accurate spinal implant placement. Hazards caused by ionizing radiation raised concern on personnel’s work life long exposure in the operating room (OR). To particularize a cumulative risk estimation of radiation of personnel and patient, depending on used methods (C-arm fluoroscopy, O-arm navigation) and patient characteristics during spinal surgery, detailed investigation of radiation exposure in a clinical setting is required. Lumbosacral dorsal spinal fusion was performed in 37 patients (19 navigated, 18 fluoroscopy) during this prospective study. Radiation exposure was measured on several body regions with thermoluminescent dosimeters on patient and OR personnel (surgeon, assistant, sterile nurse, radiology technologist). Comparison between patient characteristics and radiation exposure was included. The highest patients values were measured in the surgery field and gonads area during navigation (43.2 ± 19.4 mSv; fluoroscopy: 27.7 ± 31.3 mSv; p = 0.02), followed by the thoracic region during fluoroscopy (7.7 ± 14.8 mSv; navigation: 1.1 ± 1.0 mSv; p = 0.06), other measured regions can be considered marginal in comparison. Amongst OR personnel exposure of the surgeon was significant higher during fluoroscopy (right hand: 566 ± 560 µSv and thoracic region: 275 ± 147 µSv; followed by thyroid and forehead) compared to navigation (right finger: 49 ± 19 µSv; similar levels for all regions; p

Osteosarcoma is the most common primary bone cancer type in humans. It is predominantly found in young individuals, with a second peak later in life. The tumour is formed by malignant osteoblasts and consists of collagenous, sometimes also mineralized, bone matrix. While the morphology of osteosarcoma has been well studied, there is virtually no information about the nanostructure of the tumour and changes in mineralization on the nanoscale level. In the present paper, human bone tissue inside, next to and remote from a sclerosing osteosarcoma was studied with small angle x-ray scattering, x-ray diffraction and electron microscopy. Quantitative evaluation of nanostructure parameters was combined with high resolution, large area mapping to obtain microscopic images with nanostructure parameter contrast. It was found that the tumour regions were characterized by a notable reduction in mineral particle size, while the mineral content was even higher than that in normal bone. Furthermore, the normal preferential orientation of mineral particles along the longitudinal direction of corticalis or trabeculae was largely suppressed. Also the bone mineral crystal structure was affected: severe crystal lattice distortions were detected in mineralized tumour tissue pointing to a different ion substitution of hydroxyl apatite in tumorous tissue than in healthy tissue.

Tumour endoprostheses have facilitated limb-salvage procedures in primary bone and soft tissue sarcomas, and are increasingly being used in symptomatic metastases of the long bones. The objective of the present review was to analyse articles published over the last three years on tumour endoprostheses and to summarize current knowledge on this topic. The NCBI PubMed webpage was used to identify original articles published between January 2015 and April 2018 in journals with an impact factor in the top 25.9% of the respective category (orthopaedics, multidisciplinary sciences). The following search-terms were used: tumour endoprosthesis, advances tumour endoprosthesis, tumour megaprosthesis, prosthetic reconstruction AND tumour. We identified 347 original articles, of which 53 complied with the abovementioned criteria. Articles were categorized into (1) tumour endoprostheses in the shoulder girdle, (2) tumour endoprostheses in the proximal femur, (3) tumour endoprostheses of the knee region, (4) tumour endoprostheses in the pelvis, (5) (expandable) prostheses in children and (6) long-term results of tumour endoprostheses. The topics of interest covered by the selected studies largely matched with the main research questions stated at a consensus meeting, with survival outcome of orthopaedic implants being the most commonly raised research question. As many studies reported on the risk of deep infections, research in the future should also focus on potential preventive methods in endoprosthetic tumour reconstruction. Cite this article: EFORT Open Rev 2019;4:445-459. DOI: 10.1302/2058-5241.4.180081

Background Patients with primary malignant bone tumors are facing different challenges in their everyday lives due to improved treatment and prolonged survival. This raises the question whether and to what extent their quality of life, body image, and self-esteem is affected by their disease. The aim of this retrospective study was to analyze the quality of life, body image and self-esteem of patients with primary malignant bone tumors compared to a healthy control group. Methods A total of 56 patients (39 male, 17 female; average age 33.8 [± 14.29] years) who were treated with either osteosarcoma or Ewing-Sarcoma at the authors’ institution between Jan 1989 and May 2015 were included into the study (mean follow-up: 9.1 ± 6.6] years). The control group consisted of 58 (average age 24.4 [± 3.1] years, 31 male, 27 female) healthy medical students. Standardized questionnaires were used to assess quality of life (SF-36), body image (MBSRQ) and self-esteem (RSE-scale). Student’s t test were used for statistical analysis. Results Quality of life (SF-36) (in physical categories) and body image (MBSRQ) was significantly lower in patients with primary malignant bone tumors compared to healthy cohort (p

This case report is about myopericytomatosis, a recently described rare tumor entity with only a dozen cases found in PubMed. Histologically, this tumor is characterized by diffuse infiltration of innumerable discrete myopericytoma-like nodules composed of myoid cells in a perivascular distribution. PDGFRB mutation has been linked to myopericytomatosis as well as other myopericytic tumors. The aim of this paper is to share the clinical presentation and expand the spectrum of genetic findings. We report a case of myopericytomatosis arising around the left ankle of a 73-year-old man. MRI, biopsy, and histopathology were the main diagnostic steps. Targeted next-generation sequencing was carried out to analyze the tumor sample. We performed local excision for tumor mass reduction, as wide resection was impossible a priori based on the delicate anatomical region with important structures in close proximity. Genetic analysis revealed a missense mutation of PDGFRB. PDGFRB alteration seems to play a pathogenic role in myopericytomatosis as highlighted in previously reported cases. Currently, myopericytomatosis is best treated surgically.

Purpose Accurate placement of spinal pedicle screws (PS) is mandatory for good primary segmental stabilization allowing consequent osseous fusion, requiring judgmental experience developed during a long training process. Computer navigation offers permanent visual control during screw manipulation and has been shown to significantly lower the risk of pedicle perforation. This study aims to evaluate whether safety, accuracy, and judgmental skills in screw placement, comparable to an experienced surgeon, can be developed during training using computer navigation. Methods Lumbosacral PS were placed in 18 patients in a prospective setting, in one segment side with conventional fluoroscopy by a senior spine-surgeon, and computer navigated on the other side by a trainee without prior experience in the technique. At the beginning and at the end of the study, PS were placed freehand in solid foam models by the trainee. PS placement time, intraoperative placement revisions, PS placement accuracy on postoperative CT scans, and postoperative complications were assessed. Results Significant improvement of trainee’s PS placement accuracy (Sclafani score 8.2–8.83; p = 0.006) and time (13.3–6.8 min per screw; p = 0.005) to a similar level as the experienced surgeon state (5.2–4.1 min per screw; p = 0.39) was explored; similar improvement was explored in the foam models. The number of intraoperative placement revisions kept on a low level for surgeon (3.3–0.0%) and trainee (5.1–2.6%) during the whole study, no postoperative complications occurred. Conclusion Navigated PS insertion allows safe teaching from the early beginning of surgical training, due to steady intraoperative control on PS placement. Adequacy of PS placement is similar to screws placed by an experienced surgeon. Progress in judgmental skills in screw placement can be gained rapidly by the trainee, which can also be transferred to non-computer navigated PS placement.

Background Progression of osteoarthritis (OA) is characterized by an excessive production of matrix degrading enzymes and insufficient matrix repair. Despite of active research in this area, it is still unclear how the combination of mechanical exposure and drug therapy works. This study was done to explore the impact of the disease modifying OA drug (DMOAD) diacerein and moderate tensile strain on the anabolic metabolism and the integrin-FAK-MAPKs signal transduction cascade of OA and non-OA chondrocytes. Methods Cyclic tensile strain was applied in terms of three different intensities by the Flexcell tension system. Influence on catabolic parameters such as MMPs, ADAMTS, and IL-6 were assessed by qPCR. Changes in phosphorylation of FAK, STAT3 as well as MAP kinases were verified by western blot analysis. Intracellular calcium was measured fluorimetrically using fura-2. Results Tensile strain at moderate intensity (SM/SA profile) proved to be most efficient in terms of reducing production of matrix degrading enzyme and IL-6 expression. Treatment with diacerein by itself and diacerein in combination with SM/SA stimulation reduced phosphorylation of FAK and STAT3, which is more pronounced in OA cells. Pretreatment with diacerein for 7 days resulted in an increase in the sensitivity to Yoda1, the agonist for the mechanically activated ion channel Piezo1. However, in OA chondrocytes a significant reduction in Piezo1 expression was observed following treatment with diacerein. Conclusion Our results demonstrated for the first time that diacerein intensively intervenes in the regulation of FAK and STAT3 and influences components considered relevant for the progression of OA, even in the presence of mechanical stimulation.

Der Hauptanwendungsbereich von modularen Endoprothesen, auch Tumor- oder Megaprothesen genannt, ist die Extremitatenrekonstruktion nach Resektion von malignen Knochen- oder Weichteiltumoren. Gelegentlich wird dieser Prothesentyp auch bei Revisionseingriffen nach Versagen einer Gelenkprothese benotigt. Trotz technischer Verbesserungen und qualitatssichernder Masnahmen ist die periprothetische Infektion eine der gefurchtetsten Komplikationen. Literaturrecherche im PubMed mit dem Themenschwerpunkt Silberbeschichtungen in der Endoprothetik und deren Auswirkungen hinsichtlich Infektionsprophylaxe, Outcome und Anwendungssicherheit. Die aktuelle Literatur zeigt derzeit einen Trend, dass im Vergleich zu nichtbeschichteten Implantaten, Silberbeschichtungen bei Megaprothesen einen Vorteil hinsichtlich Revisionsraten fur septische Komplikationen haben, vor allem nach Tumorresektionen mit schlechten Weichteilverhaltnissen oder bei multimorbiden Risikopatienten. Basierend auf den Daten und Ergebnissen fruherer Publikationen, welche die Silberkonzentrationen im Blut, Serum und Urin untersucht haben, scheinen Silberbeschichtungen keine schwerwiegenden Nebenwirkungen zu haben. Einer der bekanntesten Nebeneffekte ist die lokale Argyrie. Dennoch wird eine weitere kontinuierliche Uberwachung der Silberkonzentrationen in Blut oder Serum empfohlen, da Langzeitstudien ausstehen, die die Wirksamkeit und Sicherheit von Silberbeschichtungen im weiteren Verlauf uberprufen bzw. beweisen.

Mazabraud syndrome is a rare disorder, characterized by the presence of fibrous dysplasia (FD) with associated intramuscular myxomas. Data are scarce on the prevalence, clinical features, and natural history of this disorder and outcomes. In this multicenter study, we evaluated a series of patients from 6 European centers.All centers affiliated with the European Musculo-Skeletal Oncology Society (EMSOS) were invited to include data on all patients with Mazabraud syndrome who were seen between 1980 and 2015. The study investigated the prevalence of Mazabraud syndrome, the type, severity, and localization of FD lesions in relation to myxomas, the histopathology of myxomas, and results of GNAS-mutation analysis, when available.Thirty-two patients (22 female) from 6 centers were included. The prevalence of Mazabraud syndrome was 2.2% in the combined cohort of 1,446 patients with FD, and the syndrome was diagnosed at a mean of 10.1 years after diagnosis of FD. The myxomas were predominantly localized in the upper leg. Excision was performed in 20 patients, recurrence occurred in 6 of these patients (30%) at a median of 8.5 years (range, 1.9 to 16.0 years), and revision surgery was necessary in 5 (25%). High cellularity of myxomas was associated with recurrence (p0.05). A GNAS mutation was identified in the myxoma tissue of 5 (83%) of 6 patients with GNAS-mutation analysis.This study is the first, to our knowledge, to provide data on the prevalence of Mazabraud syndrome in a relatively large cohort. Although the outcomes of surgical resection were good, a quarter of the patients required revision surgery despite clear resection margins. High cellularity of myxomas was associated with recurrence. GNAS mutations were identified in 83% (5 of 6), emphasizing the shared origin of FD and myxomas. Our data show that patients with FD who have disproportionate complaints, irrespective of FD type, extent, or severity, should be investigated for the possible presence of myxomas.Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Ankle is the most common site of hardware removal, mainly performed within 12 months of the primary surgery. The prominence of the metallic hardware is a frequent cause of pain after fracture fixation. Over the last decade, the development of bioresorbable materials based on magnesium (Mg) has increased. Bioresorbable metals aim to avoid a second surgery for hardware removal. Methods Twenty patients with isolated, bimalleolar, or trimalleolar ankle fractures were treated with bioresorbable screws made of Mg, 0.45wt% calcium (Ca) and 0.45wt% zinc (Zn) (ZX00). Patient-reported outcome measures (PROMs) including visual analogue scale (VAS) for pain, the presence of complications 6 and 12 months after surgery and the AOFAS scale after 12 months were reported. The functional outcomes were analysed through the range of motion (ROM) of the ankle joint with a standard goniometer. Degradation products and the bioresorbability of the screws were evaluated using plane radiographs. Results One patient was lost to follow-up. All patients were free of pain, no complications, shoe conflict or misalignement were reported after 12 months of follow-up. No Mg screws were surgically removed. An additional fixation of the distal fibula or the dorsal tibial fragment with conventional titanium implants (Ti) was performed in 17 patients. Within 12 months after primary refixation, 12 of these patients (71%) underwent a second surgery for Ti hardware removal. The mean AOFAS score was 89.8±7.1 and the difference between the treated and the non-treated site in the ROM of the talocrural joint was 2°±11° after 12 months. Radiolucent areas around the screws were attributed to degradation and did not affect clinical or functional outcomes. After one year, the Mg screw heads could not be detected in the plane radiographs of 17 patients which suggests that the majority of the screw head is degraded without introducing adverse reactions. Conclusions At 6 and 12 months, the bioresorbable Mg screws show excellent PROMs without complications or need for screw removal. The resorbability of the screw heads in most of the patients after one year could also provide an advantage over conventional bio-inert implants by avoiding related skin irritation due for instance to shoe conflict.

Introduction The aim of this study was to compare the use of mobile-bearing, fixed-bearing, posterior-stabilized (PS) and medial pivot design to describe epidemiological differences and subsequent outcomes. Materials and methods A systematic literature search was performed using the NORE website to identify the relevant arthroplasty registers. Inclusion criteria were the following: (1) reports had to be publicly available, (2) reports had to be written in German or English language, (3) differentiation between mobile- and fixed-bearing, posterior-stabilized, and if possible, medial pivot designs had to be possible from the present reports, and (4) data had to be reported for at least three consecutive years and the latest report had to be from the year 2020 to retrieve recent data. Results Six registries (England and Wales, Australia, Norway, New Zealand, Germany, Switzerland) offered sufficient data according to the inclusion criteria. In all countries, the dominant type of bearing used for total knee arthroplasty (TKA) was fixed-bearing, with percentages ranging from 60.8% to 84.1% in 2018, 63.6% to 85.7% in 2019 and 66.2% to 87.4% in 2020. A large variation was observed concerning mobile-bearing design, which showed a range from 2.8% to 39.2% in 2018, 2.6% to 36.4% in 2019 and 2.9% to 33.8% in 2020. Some variation was found regarding the use of PS TKA, as its percentage frequency ranged from 9.7% to 29.2% in 2018, 9.8% to 29.4% in 2019 and 10.1% to 28.5% in 2020. Medial pivot design had a share of 9.1% in 2018, 8.6% in 2019 and 8.4% in 2020 in Australia, while it only accounted for 1.4% in 2018, 2.1% in 2019 and 2.5% in 2020 in Germany. Conclusion The comparison of arthroplasty registers from England and Wales, Australia, Norway, New Zealand, Germany and Switzerland revealed large differences regarding the application of posterior-stabilized designs, but also common ground considering the overwhelming use of fixed-bearing inserts, which, when inserted correctly, eradicate the potential complication of bearing dislocation. Arthroplasty registers offer a real-world clinical perspective with the aim to improve quality and patient safety.

Background This study aimed at analysing risk factors for development of acute compartment syndrome (ACS) in tibial plateau fractures, and to construct a nomogram predicting ACS-risk. Patients and Methods 243 patients (102 males; mean age: 50.7 [range: 18-85] years) with 253 tibial plateau fractures treated between 2010 and 2019 at a level-1 trauma centre were retrospectively included. Uni- and multivariate logistic regression analysis with odds ratios (OR) were performed to assess variables predicting ACS. Based on the multivariate model, ROC curve, Youden index, and nomogram were constructed. Results ACS developed in 23 patients (9.1%), with risk factors being male gender (OR: 10.606; p0.001), BMI (OR: 1.084; p = 0.048), polytrauma (OR: 4.085; p = 0.003), and Schatzker type IV-VI fractures (OR: 6.325; p = 0.004). Age, ASA score, diabetes, renal insufficiency, hypertension, smoking or open fracture were not significantly associated with ACS-risk (all p0.05). In the multivariate analysis, male gender (OR: 7.392; p = 0.002), and Schatzker type IV-VI fractures (OR: 5.533; p = 0.009) remained independent negative ACS-predictors, irrespective of polytrauma (p = 0.081), or BMI (p = 0.194). Area under the ROC curve was 0.840. Youden index revealed a cut-off value of ≥ 18%, upon which patients are at extremely high risk for ACS. Conclusions Particular attention should be paid to male patients with high-energy fractures of the tibial plateau towards any signs of ACS of the affected extremity to initiate early treatment. The compiled nomogram, consisting of four easily quantifiable clinical variables, may be used in clinical practice to individually predict ACS risk. Any risk score ≥ 18% should prompt critical monitoring towards ACS, or even prophylactic fasciotomy during primary surgery.

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 p = 0.012) templating was significantly different from the definitively used cup size. The difference between the 2D-planned and implanted stem size (p p = 0.181). Three-dimensional templating showed significantly higher accuracy than 2D templating in terms of cup size (1.1 ± 1.4 versus 1.7 ± 1.8; p = 0.007) and stem size (0.3 ± 0.6 versus 0.7 ± 0.7; p With increasing body mass index (BMI), 2D templating of the stem became more inaccurate (p = 0.041). Remarkably, 3D templating remained accurate for all components (stem, p = 0.533; cup, p = 0.479) despite increasing BMI. Conclusion Despite extended planning time and increased exposure to radiation, 3D-based planning showed higher accuracy than 2D templating, especially in obese patients. On the basis of our results, we believe that 3D-based pre-operative planning in THA is justifiable and beneficial in patients with increased BMI. Level of Evidence III.

Nuclear magnetic resonance therapy (NMRT) is discussed as a participant in repair processes regarding cartilage and as an influence in pain signaling. To substantiate the application of NMRT, the underlying mechanisms at the cellular level were studied. In this study microRNA (miR) was extracted from human primary healthy and osteoarthritis (OA) chondrocytes after NMR treatment and was sequenced by the Ion PI Hi-Q™ Sequencing 200 system. In addition, T/C-28a2 chondrocytes grown under hypoxic conditions were studied for IL-1β induced changes in expression on RNA and protein level. HDAC activity an NAD(+)/NADH was measured by luminescence detection. In OA chondrocytes miR-106a, miR-27a, miR-34b, miR-365a and miR-424 were downregulated. This downregulation was reversed by NMRT. miR-365a-5p is known to directly target HDAC and NF-ĸB, and a decrease in HDAC activity by NMRT was detected. NAD+/NADH was reduced by NMR treatment in OA chondrocytes. Under hypoxic conditions NMRT changed the expression profile of HIF1, HIF2, IGF2, MMP3, MMP13, and RUNX1. We conclude that NMRT changes the miR profile and modulates the HDAC and the NAD(+)/NADH signaling in human chondrocytes. These findings underline once more that NMRT counteracts IL-1β induced changes by reducing catabolic effects, thereby decreasing inflammatory mechanisms under OA by changing NF-ĸB signaling.

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication., Highlights • This consensus paper provides key recommendations on the management of epithelioid hemangioendothelioma (EHE). • Recommendations followed a consensus meeting between experts and a representative of the EHE advocacy group and SPAEN. • Authorship includes a multidisciplinary group of experts from different institutions from Europe, North America and Asia.