Growth in the Lower Limb Following Chemotherapy for a Malignant Primary Bone Tumour: A Straight-Line Graph

Purpose. The aim of this paper was to assess the growth in the unaffected lower limb of children who had received chemotherapy for a malignant primary bone tumour around the knee

Longitudinal Growth Following Treatment for Osteosarcoma

Purpose. The purpose of this study was to analyse the height at diagnosis and growth in 72 skeletally immature children who had been treated for osteosarcoma in the area of the knee

Quality of Life in Children Following Treatment for a Malignant Primary Bone Tumour Around the Knee

Purpose. We report on the quality of life following treatment for a malignant primary bone tumour around the knee in skeletally immature children

Machine learning models based on routinely sampled blood tests can predict the presence of malignancy amongst patients with suspected musculoskeletal malignancy.

This study explores the possibility of using routinely taken blood tests in the diagnosis and triage of patients with suspected musculoskeletal malignancy. A retrospective study was performed on results of patients who had presented for assessment to a regional musculoskeletal tumour unit. Blood results of patients with a histologically confirmed diagnosis between 2010 and 2020 were retrieved. 33 distinct blood tests were available for model forming. Results were standardised by calculating z-scores. Data were split into a training set (70%) and a test set (30%). The training set was balanced by resampling underrepresented classes. The random forest algorithm performed best and was selected for model forming. Receiver operating characteristic curves were used to find the optimum threshold. Models were calibrated and performance metrics evaluated with confusion tables. 2371 patients formed the study population. 1080 had a malignant diagnosis in one of three categories: sarcoma, metastasis, or haematological malignancy. 1291 had a benign condition. Metastasis could be predicted with an accuracy of 79% (AUC 87%, sensitivity 79%, specificity 80% NPV 91%). Haematological malignancy accuracy 79% (AUC 81%, sensitivity 77%, specificity 79%, NPV 97%). Sarcoma accuracy 64% (AUC 73%, sensitivity 76%, specificity 61%, NPV 88%) and all malignancy accuracy 74% (AUC 80%, sensitivity 72%, specificity 75%, NPV 76%). Routinely performed blood tests can be useful in triage of musculoskeletal tumours and can be used to predict presence of musculoskeletal malignancy. [Abstract copyright: Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.

Circulating tumour DNA is a promising biomarker for risk stratification of central chondrosarcoma with IDH1/2 and GNAS mutations

Chondrosarcoma (CS) is a rare tumour type and the most common primary malignant bone cancer in adults. The prognosis, currently based on tumour grade, imaging and anatomical location, is not reliable, and more objective biomarkers are required. We aimed to determine whether the level of circulating tumour DNA (ctDNA) in the blood of CS patients could be used to predict outcome. In this multi-institutional study, we recruited 145 patients with cartilaginous tumours, of which 41 were excluded. ctDNA levels were assessed in 83 of the remaining 104 patients, whose tumours harboured a hotspot mutation in IDH1/2 or GNAS. ctDNA was detected pre-operatively in 31/83 (37%) and in 12/31 (39%) patients postoperatively. We found that detection of ctDNA was more accurate than pathology for identification of high-grade tumours and was associated with a poor prognosis; ctDNA was never associated with CS grade 1/atypical cartilaginous tumours (ACT) in the long bones, in neoplasms sited in the small bones of the hands and feet or in tumours measuring less than 80 mm. Although the results are promising, they are based on a small number of patients, and therefore, introduction of this blood test into clinical practice as a complementary assay to current standard-of-care protocols would allow the assay to be assessed more stringently and developed for a more personalised approach for the treatment of patients with CS

Using nanopore sequencing to identify bacterial infection in joint replacements: a preliminary study

This project investigates if third-generation genomic sequencing can be used to identify the species of bacteria causing prosthetic joint infections (PJIs) at the time of revision surgery. Samples of prosthetic fluid were taken during revision surgery from patients with known PJIs. Samples from revision surgeries from non-infected patients acted as negative controls. Genomic sequencing was performed using the MinION device and the rapid sequencing kit from Oxford Nanopore Technologies. Bioinformatic analysis pipelines to identify bacteria included Basic Local Alignment Search Tool, Kraken2 and MinION Detection Software, and the results were compared with standard of care microbiological cultures. Furthermore, there was an attempt to predict antibiotic resistance using computational tools including ResFinder, AMRFinderPlus and Comprehensive Antibiotic Resistance Database. Bacteria identified using microbiological cultures were successfully identified using bioinformatic analysis pipelines. Nanopore sequencing and genomic classification could be completed in the time it takes to perform joint revision surgery (2–3 h). Genomic sequencing in this study was not able to predict antibiotic resistance in this time frame, this is thought to be due to a short-read length and low read depth. It can be concluded that genomic sequencing can be useful to identify bacterial species in infected joint replacements. However, further work is required to investigate if it can be used to predict antibiotic resistance within clinically relevant timeframes

HST/ACS Imaging of Omega Centauri: Optical Counterpart for the Quiescent Low-Mass X-Ray Binary

We report the discovery of an optical counterpart to a quiescent neutron star in the globular cluster Omega Centauri (NGC 5139). The star was found as part of our wide-field imaging study of Omega Cen using the Advanced Camera for Surveys (ACS) on Hubble Space Telescope. Its magnitude and color (R_625 = 25.2, B_435 - R_625 = 1.5) place it more than 1.5 magnitudes to the blue side of the main sequence. Through an H-alpha filter it is ~ 1.3 magnitudes brighter than cluster stars of comparable M_625 magnitude. The blue color and H-alpha excess suggest the presence of an accretion disk, implying that the neutron star is accreting from a binary companion and is thus a quiescent low-mass X-ray binary. If the companion is a main-sequence star, then the faint absolute magnitude (M_625 ~ 11.6) constrains it to be of very low mass (M <~ 0.14 Msolar). The faintness of the disk (M_435 ~ 13) suggests a very low rate of accretion onto the neutron star. We also detect 13 probable white dwarfs and three possible BY Draconis stars in the 20" x 20" region analyzed here, suggesting that a large number of white dwarfs and active binaries will be observable in the full ACS study.Comment: Accepted for Publication in the Astrophysical Journal. 5 pages, 4 figures, 1 table, uses emulateapj.sty. Figures 1 and 3 at reduced resolution. New version contains revised magnitude calibration

A genetic model for central chondrosarcoma evolution correlates with patient outcome

Background Central conventional chondrosarcoma (CS) is the most common subtype of primary malignant bone tumour in adults. Treatment options are usually limited to surgery, and prognosis is challenging. These tumours are characterised by the presence and absence of IDH1 and IDH2 mutations, and recently, TERT promoter alterations have been reported in around 20% of cases. The effect of these mutations on clinical outcome remains unclear. The purpose of this study was to determine if prognostic accuracy can be improved by the addition of genomic data, and specifically by examination of IDH1, IDH2, and TERT mutations. Methods In this study, we combined both archival samples and data sourced from the Genomics England 100,000 Genomes Project (n = 356). Mutations in IDH1, IDH2, and TERT were profiled using digital droplet PCR (n = 346), whole genome sequencing (n=68), or both (n = 64). Complex events and other genetic features were also examined, along with methylation array data (n = 84). We correlated clinical features and patient outcomes with our genetic findings. Results IDH2-mutant tumours occur in older patients and commonly present with high-grade or dedifferentiated disease. Notably, TERT mutations occur most frequently in IDH2-mutant tumours, although have no effect on survival in this group. In contrast, TERT mutations are rarer in IDH1-mutant tumours, yet they are associated with a less favourable outcome in this group. We also found that methylation profiles distinguish IDH1- from IDH2-mutant tumours. IDH wild-type tumours rarely exhibit TERT mutations and tend to be diagnosed in a younger population than those with tumours harbouring IDH1 and IDH2 mutations. A major genetic feature of this group is haploidisation and subsequent genome doubling. These tumours evolve less frequently to dedifferentiated disease and therefore constitute a lower risk group. Conclusions Tumours with IDH1 or IDH2 mutations or those that are IDHwt have significantly different genetic pathways and outcomes in relation to TERT mutation. Diagnostic testing for IDH1, IDH2, and TERT mutations could therefore help to guide clinical monitoring and prognostication