Increased zinc accumulation in mineralized osteosarcoma tissue measured by confocal synchrotron radiation micro X-ray fluorescence analysis

Abnormal tissue levels of certain trace elements such as zinc (Zn) were reported in various types of cancer. Little is known about the role of Zn in osteosarcoma. Using confocal synchrotron radiation micro X-ray fluorescence analysis, we characterized the spatial distribution of Zn in high-grade sclerosing osteosarcoma of nine patients (four women/five men; seven knee/one humerus/one femur) following chemotherapy and wide surgical resection. Levels were compared with adjacent normal tissue. Quantitative backscattered electron imaging as well as histological examinations was also performed. On average, the ratio of medians of Zn count rates (normalized to calcium) in mineralized tumor tissue was about six times higher than in normal tissue. There was no difference in Zn levels between tumor fraction areas with a low fraction and a high fraction of mineralized tissue, which were clearly depicted using quantitative backscattered electron imaging. Moreover, we found no correlation between the Zn values and the type of tumor regression according to the Salzer-Kuntschik grading. The underlying mechanism of Zn accumulation remains unclear. Given the emerging data on the role of trace elements in other types of cancer, our novel results warrant further studies on the role of trace elements in bone cancer

A novel machine learning-derived radiotranscriptomic signature of perivascular fat improves cardiac risk prediction using coronary CT angiography

Background: Coronary inflammation induces dynamic changes in the balance between water and lipid content in perivascular adipose tissue (PVAT), as captured by perivascular Fat Attenuation Index (FAI) in standard coronary CT angiography (CCTA). However, inflammation is not the only process involved in atherogenesis and we hypothesized that additional radiomic signatures of adverse fibrotic and microvascular PVAT remodelling, may further improve cardiac risk prediction. Methods and results: We present a new artificial intelligence-powered method to predict cardiac risk by analysing the radiomic profile of coronary PVAT, developed and validated in patient cohorts acquired in three different studies. In Study 1, adipose tissue biopsies were obtained from 167 patients undergoing cardiac surgery, and the expression of genes representing inflammation, fibrosis and vascularity was linked with the radiomic features extracted from tissue CT images. Adipose tissue wavelet-transformed mean attenuation (captured by FAI) was the most sensitive radiomic feature in describing tissue inflammation (TNFA expression), while features of radiomic texture were related to adipose tissue fibrosis (COL1A1 expression) and vascularity (CD31 expression). In Study 2, we analysed 1391 coronary PVAT radiomic features in 101 patients who experienced major adverse cardiac events (MACE) within 5 years of having a CCTA and 101 matched controls, training and validating a machine learning (random forest) algorithm (fat radiomic profile, FRP) to discriminate cases from controls (C-statistic 0.77 [95%CI: 0.62–0.93] in the external validation set). The coronary FRP signature was then tested in 1575 consecutive eligible participants in the SCOT-HEART trial, where it significantly improved MACE prediction beyond traditional risk stratification that included risk factors, coronary calcium score, coronary stenosis, and high-risk plaque features on CCTA (Δ[C-statistic] = 0.126, P  Conclusion: The CCTA-based radiomic profiling of coronary artery PVAT detects perivascular structural remodelling associated with coronary artery disease, beyond inflammation. A new artificial intelligence (AI)-powered imaging biomarker (FRP) leads to a striking improvement of cardiac risk prediction over and above the current state-of-the-art. </p

Data from: Outcome after reconstruction of the proximal tibia – complications and competing risk analysis

Background and Objectives: The proximal tibia (pT) is a common site for bone tumors. Improvements in imaging, chemotherapy and surgical technique made limb salvage surgery the treatment of choice. Yet, reconstructions of the pT have been associated with less favorable outcome compared to other parts of the extremities. The aim of this study was to evaluate the outcome of patients with a modular endoprosthetic reconstruction of the pT. Methods: Eighty-one consecutive patients with an average age of 29 years underwent endoprosthetic reconstruction of the pT. Postoperative complications were categorized according to the ISOLS classification, and revision-free survival until first complication (any Type 1–5), soft tissue failure (Type 1), aseptic loosening (Type 2), structural failure (Type 3), infection (Type 4), and local tumor progression (Type 5) was estimated by using a Fine-Gray model for competing risk analyses for univariate and multivariable regression with Firth’s bias correction. Results: A total of 45 patients (56%) had at least one complication. Cumulative incidence for complication Types 1 to 5 at 5 years with death and amputation as competing events revealed a risk of 41% for the first complication, 14% for Type 1, 16% for Type 2, 11% for Type 3, 17% for Type 4, and 1% for Type 5. Conclusion: Despite inclusion of amputation and death as strong competing events, pT replacements are still associated with a high risk of postoperative failures. The results suggest that infection and soft tissue failures (Type 1 and 5) seem to depend from each other. Sufficient soft tissue reconstruction and closure allow better function and reduce the risk of infection as the most prominent complication. The use of a rotating hinge design has significantly reduced structural failures over time

Serum Inflammatory Biomarkers in the Diagnosis of Periprosthetic Joint Infections

Accurate preoperative diagnosis of periprosthetic joint infections (PJIs) can be very challenging, especially in patients with chronic PJI caused by low-virulence microorganisms. Serum parameters, such as serum C-reactive protein (CRP) or the erythrocyte sedimentation rate (ESR), are—among other diagnostic test methods—widely used to distinguish septic from aseptic failure after total hip or knee arthroplasty and are recommended by the AAOS in the preoperative setting. However, they are systemic parameters, and therefore, unspecific. Nevertheless, they may be the first and occasionally the only preoperative indication, especially when clinical symptoms are lacking. They are easy to obtain, cheap, and are available worldwide. In the last decade, different novel serum biomarkers (percentage of neutrophils, neutrophils to lymphocytes ratio, platelet count to mean platelet volume ratio, fibrinogen, D-Dimer, Il-6, PCT) were investigated to find a more specific and accurate serum parameter in the diagnosis of PJI. This article reviews the diagnostic value of established (serum CRP, ESR, WBC) and ‘novel’ serum inflammatory biomarkers (fibrinogen, D-dimer, interleukin-6 (IL-6), procalcitonin, percentage of neutrophils (%N), neutrophils to lymphocytes ratio (NLR), platelet count to mean platelet volume ratio (PC/mPV)) for the preoperative diagnosis of periprosthetic joint infections

Data from: Oncological and surgical outcome after treatment of pelvic sarcomas

Background and Objectives. Treatment of pelvic tumors remains challenging due to complex anatomy, poor oncological outcome and high complication rates. We sought to investigate the long-term oncological and surgical outcome of these patients. Methods. Between 1980 and 2012, 147 patients underwent surgical treatment for pelvic sarcoma. Histological diagnosis was Chondrosarcoma in 54, Ewing's Sarcoma/PNET in 37, Osterosarcoma in 32 and others in 24 patients. Statistical analysis for the evaluation of oncological and surgical outcome was performed by applying Cox proportional hazards regression and Fine-Gray regression models for competing risk (CR) endpoints. Results. The estimated overall survival (OS) to death was 80%, 45% and 37% at 1, 5 and 10 years, respectively. Univariate analyses revealed a statistically significant unadjusted influence of age age (p=0.038; HR=1.01), margin (p=0.043; HR=0.51) and grade (p=0.001; HR=2.27) on OS. Considering the multivariable model, grade (p=0.005; HR=3.04) and tumor volume (p=0.014; HR=1.18) presented themselves as independent prognostic factors on OS. CR analysis showed a cumulative incidence for major complication of 31% at 5 years. Endoprosthetic reconstruction had a higher risk for experiencing a major complication (p<0.0001) and infection (p=0.001). Conclusions. Pelvic resections are still associated with a high incidence of complications. Patients with pelvic reconstruction and high volume tumors are especially at risk. Consequently, a cautious decision-making process is necessary when indicating pelvic reconstruction, although a restrictive approach to pelvic reconstruction is not necessarily reasonable when the other option is major amputation

Interface Management between General Practitioners and Rheumatologists-Results of a Survey Defining a Concept for Future Joint Recommendations.

OBJECTIVE:To measure the views of general practitioners (GPs) and rheumatologists in a nationwide evaluation, so as to optimise their cooperation in managing patients with inflammatory rheumatic diseases. METHODS:A questionnaire covering aspects of collaboration was sent, both by mail and/or by email, to all GPs and rheumatologists in Austria. Topics covered were (i) examinations and interventions to be performed before referral, (ii) the spectrum of diseases to be referred, and (iii) the role of GPs in follow-up and continuous management of patients. RESULTS:1,229 GPs of the 4,016 GPs (31%) and 110 of the 180 rheumatologists (61%) responded to the questionnaire. In cases of suspected arthritis, 99% of the GPs and 92% of the rheumatologists recommended specific laboratory tests, and 92% and 70%, respectively, recommended X-rays of affected joints before referral. Rheumatoid arthritis and spondyloarthritis, psoriatic arthritis and connective tissue disease were unanimously seen as indications for referral to a rheumatologist. Only 12% of rheumatologists felt responsible for the treatment of hand osteoarthritis and fibromyalgia. 80% of GPs and 85% of rheumatologists were of the opinion that treatment with disease-modifying drugs should be initiated by a specialist. Subsequent drug prescription and administration by GPs was supported by a majority of GPs and rheumatologists, with a concomitant rheumatologist follow-up every three to six months. CONCLUSION:The considerable consensus between the two professional groups constitutes a solid base for future joint recommendations, with the aim to accelerate the diagnostic process and the initiation of adequate therapy

LARS® band and tube for extensor mechanism reconstructions in proximal tibial modular endoprostheses after bone tumors.

UNLABELLED Wide tumor resections around the proximal tibia (pT) are related to compromised function and high complication rates. This retrospective study aims to present the technique employed as well as functional and surgical outcomes of patients undergoing a Ligament Advanced Reinforcement System (LARS®) reconstruction of the knee extensor apparatus after tumor resection and modular endoprosthetic reconstruction of the proximal tibia. Twenty-five patients who received an artificial ligament after pT resection (11 men and 14 women; mean age, 29years; range 11 to 75years, with a minimum follow-up of 24months) were analyzed regarding the ISOLS failure mode classification. Twenty patients received LARS® during primary surgery, five patients during a revision of a pT modular endoprosthesis. LARS® was available as a band or a tube. The mean extension lag was nine degrees (range, 0 to 30°), the mean flexion was 103° (range, 60 to 130°). The mean extension lag and active flexion in primary implanted LARS were 7.8° and 101° versus secondarily implanted 45° and 115° (p<0.0001; p=0.15). Eleven out of 14 primary implanted LARS® band/tubes (71%) did well with extension lag (0 to 10°). LARS® usage as a band or as a tube showed similar results. The estimated five-year survival of LARS® was 92%. The median survival of LARS® implanted primarily was better than in the case of secondary implantation (p=0.006). Extensor mechanism reconstruction by LARS® band or tube shows excellent function and satisfactory implant survival after primary reconstruction of the extensor mechanism after proximal tibia resection. We experienced no LARS® rupture for only mechanical reasons. LEVEL OF EVIDENCE Level IV retrospective study

PLOS One / Outcome after Reconstruction of the Proximal Tibia Complications and Competing Risk Analysis

Background and Objectives The proximal tibia (pT) is a common site for bone tumors. Improvements in imaging, chemotherapy and surgical technique made limb salvage surgery the treatment of choice. Yet, reconstructions of the pT have been associated with less favorable outcome compared to other parts of the extremities. The aim of this study was to evaluate the outcome of patients with a modular endoprosthetic reconstruction of the pT. Methods Eighty-one consecutive patients with an average age of 29 years underwent endoprosthetic reconstruction of the pT. Postoperative complications were categorized according to the ISOLS classification, and revision-free survival until first complication (any Type 15), soft tissue failure (Type 1), aseptic loosening (Type 2), structural failure (Type 3), infection (Type 4), and local tumor progression (Type 5) was estimated by using a Fine-Gray model for competing risk analyses for univariate and multivariable regression with Firths bias correction. Results A total of 45 patients (56%) had at least one complication. Cumulative incidence for complication Types 1 to 5 at 5 years with death and amputation as competing events revealed a risk of 41% for the first complication, 14% for Type 1, 16% for Type 2, 11% for Type 3, 17% for Type 4, and 1% for Type 5. Conclusion Despite inclusion of amputation and death as strong competing events, pT replacements are still associated with a high risk of postoperative failures. The results suggest that infection and soft tissue failures (Type 1 and 5) seem to depend from each other. Sufficient soft tissue reconstruction and closure allow better function and reduce the risk of infection as the most prominent complication. The use of a rotating hinge design has significantly reduced structural failures over time.(VLID)492415

International Orthopaedics / Measurement considerations on examiner-dependent factors in the ultrasound assessment of developmental dysplasia of the hip

Purpose The standardized sonographic hip screening according to Graf has increased reliability and comparability of measurements in the screening of developmental dysplasia of the hip (DDH). However, examiner dependent factors have been discussed to influence sonographic measurements. The objectives of this study were to examine the tolerance of the transducer positioning and to analyse the impact of transducer inclinations on Grafs hip grading system. Materials and methods Twenty-four hips in consecutive newborns were screened sonographically in combination with an optoelectronic motion capture system to trace transducer positions in space. Subsequently five defined inclinations of the transducer relative to Grafs neutral transducer position were analysed, giving a total of 144 sonographic images. Results We found a permissible transducer inclination in the axial plane of 8.8 to anterior and 8.1 to posterior. In the frontal plane we found a permissible inclination of 15.4 to caudal and 7.2 to cranial. The impact on the -angle was significant for posterior-cranial (p < 0.001), cranial (p = 0.009), and caudal (p < 0.001) inclined transducer positions. The effect on the results according to Grafs grading system was significant for the caudal inclination of the transducer position (p < 0.001). Conclusion Our findings show that the standardized plane defined by Grafs criteria allows notable inclinations of the transducer positions. Transducer inclinations show an impact on measurement results, which are clinically relevant. Those effects cannot be ruled out using Grafs ultrasound criteria alone. The examiner should pay attention to avoid transducer inclinations in the frontal plane and a combination of posterior and cranial inclination.(VLID)354443