Postoperative Functional Assessment in Patients with Tumors Around the Knee Treated with Endoprosthetic Reconstruction: A Multicenter Retrospective Cohort Study.

OBJECTIVES: The restoration of as much normal function as possible has become an important goal following the endoprosthetic reconstruction. The objective of this study was to assess the functional outcome after endoprosthetic reconstruction for tumors around the knee and to explore prognostic factors of functional outcome. METHODS: We retrospectively collected data on patients who underwent tumor prosthetic replacements consecutively. Musculoskeletal Tumour Society score and Toronto Extremity Salvage Score were used to assess the functional outcome at 1, 3, 6, 12, and 24 months after surgery. The logistic model was used to select factors that had potential predictive value for postoperative function. Potential prognostic factors included age, gender, tumor site, type of tumor, length of bone resection, type of prosthesis, length of prosthetic stem, chemotherapy, pathological fracture, and body mass index. RESULTS: At the 24 months after surgery, the mean musculoskeletal tumor society (MSTS) score was 81.4% and the mean Toronto extremity salvage score (TESS) was 83.6%. At the last follow-up, 68% of patients and 73% of patients received perfect or good MSTS score and TESS score, respectively. The multivariate analysis according to ordered-logit model showed that age < 35 years, distal femoral prosthesis, and length of bone resection < 14 cm were independent prognostic factors of better functional outcome. CONCLUSIONS: Endoprosthetic reconstruction may provide good functional results for most patients. Younger patients with distal femoral prosthesis and shorter resection of bone (on the premise of complete resection of tumor) are more likely to obtain satisfactory functional results after surgery.

A Method of Bone-Metastatic Tumor Progression Assessment in Mice Using Longitudinal Radiography.

Many types of solid tumors metastasize to the bone, where it causes significant morbidity and mortality in patients with advanced disease. Bone metastases are not only incurable but also affect bone health which impairs patients' quality of life. In order to understand the mechanisms and develop effective treatments for bone-metastatic disease, it is first necessary to develop animal models that permit the assessment of tumor growth in the bone and progressive structural changes of the bone simultaneously. Longitudinal analysis of bone tumor progression is generally performed by bioluminescent imaging; however, this method is not able to assess progressive structural changes of the bone. Here, we describe a simple method for assessment of bone lesions using a scoring system that takes into account disease burden and bone destruction using longitudinal radiographs.

Bone Phenotyping Approaches in Human, Mice and Zebrafish - Expert Overview of the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork").

A synoptic overview of scientific methods applied in bone and associated research fields across species has yet to be published. Experts from the EU Cost Action GEMSTONE ("GEnomics of MusculoSkeletal Traits translational Network") Working Group 2 present an overview of the routine techniques as well as clinical and research approaches employed to characterize bone phenotypes in humans and selected animal models (mice and zebrafish) of health and disease. The goal is consolidation of knowledge and a map for future research. This expert paper provides a comprehensive overview of state-of-the-art technologies to investigate bone properties in humans and animals - including their strengths and weaknesses. New research methodologies are outlined and future strategies are discussed to combine phenotypic with rapidly developing -omics data in order to advance musculoskeletal research and move towards "personalised medicine".

Correlation between the γ passing rates of IMRT plans and the volumes of air cavities and bony structures in head and neck cancer.

BACKGROUND: Both patient-specific dose recalculation and γ passing rate analysis are important for the quality assurance (QA) of intensity modulated radiotherapy (IMRT) plans. The aim of this study was to analyse the correlation between the γ passing rates and the volumes of air cavities (Vair) and bony structures (Vbone) in target volume of head and neck cancer. METHODS: Twenty nasopharyngeal carcinoma and twenty nasal natural killer T-cell lymphoma patients were enrolled in this study. Nine-field sliding window IMRT plans were produced and the dose distributions were calculated by anisotropic analytical algorithm (AAA), Acuros XB algorithm (AXB) and SciMoCa based on the Monte Carlo (MC) technique. The dose distributions and γ passing rates of the targets, organs at risk, air cavities and bony structures were compared among the different algorithms. RESULTS: The γ values obtained with AAA and AXB were 95.6 ± 1.9% and 96.2 ± 1.7%, respectively, with 3%/2 mm criteria (p > 0.05). There were significant differences (p < 0.05) in the γ values between AAA and AXB in the air cavities (86.6 ± 9.4% vs. 98.0 ± 1.7%) and bony structures (82.7 ± 13.5% vs. 99.0 ± 1.7%). Using AAA, the γ values were proportional to the natural logarithm of Vair (R2 = 0.674) and inversely proportional to the natural logarithm of Vbone (R2 = 0.816). When the Vair in the targets was smaller than approximately 80 cc or the Vbone in the targets was larger than approximately 6 cc, the γ values of AAA were below 95%. Using AXB, no significant relationship was found between the γ values and Vair or Vbone. CONCLUSION: In clinical head and neck IMRT QA, greater attention should be paid to the effect of Vair and Vbone in the targets on the γ passing rates when using different dose calculation algorithms.

Comparative cytological and histological assessment of 828 primary soft tissue and bone lesions, and proposal for a system for reporting soft tissue cytopathology.

INTRODUCTION: The aim of the study was to evaluate the diagnostic utility of fine needle aspiration (FNA) cytology and core needle biopsies (CNBs) in a series of primary soft tissue and bone lesions and to test a possible system for reporting results of FNA cytology of soft tissue lesion. METHODS: This retrospective study encompassed 828 primary soft tissue and bone lesions, analysed with FNA, CNB and/or surgical specimen in order to perform sensitivity/specificity as well as accuracy analyses. The series was then used to test a system for reporting soft tissue cytopathology with six categories and the risk of malignancy in each category was calculated. RESULTS: With a malignant diagnosis defined as positive test result, FNA and CNB analysis showed sensitivity of 87% and 94%, respectively, and specificity of 89% and 95%, respectively. FNA and CNB analyses identified the correct histopathological entity of the examined lesion in 55% and 66%, respectively. The risk of malignancy within the tested categories was non-diagnostic 42%, non-neoplastic 0%, atypia of unknown significance 46%, neoplasm benign 3%, neoplasm of unknown malignant potential 27%, suspicious for malignancy 72% and malignant 97%. CONCLUSION: FNA cytology is a suitable tool to determine the malignant potential of a sampled soft tissue/bone lesion but is inferior to CNB in defining the correct entity. A standardised reporting system might improve the clinical management of patients with soft tissue tumours examined primarily by FNA cytology.

Bone metastasis and skeletal-related events in patients with solid cancer: A Korean nationwide health insurance database study.

Bone is one of the most common sites of metastasis from advanced solid tumors. Bone metastasis is a leading cause of pain and increases the risk of skeletal-related events (SREs) in cancer patients. In addition to affecting the quality of life, it also increases the medical costs and mortality risk. We aimed to examine the occurrence of bone metastasis and SREs in Korean cancer patients using a nationwide health database. Using claims data from the National Health Insurance Service-National Sample Cohort (2002-2013), we extracted the data of bone metastasis patients diagnosed with any of the seven major cancers in Korea from January 2002 to December 2010. Selected SREs included pathologic fracture, spinal cord compression, radiation therapy, and palliative bone surgery. We used time-to-event analysis to estimate patient survival after bone metastasis. A total of 21,562 newly diagnosed cancer patients were identified; bone metastases developed in 1,849 patients (breast cancer, 18.8%; prostate cancer, 17.5%; lung cancer, 13.7%). The median time from primary cancer diagnosis to bone metastasis was 18.9 months. The cumulative incidence of SREs was 45.1% in all bone metastasis patients. The most common cancer type was lung cancer (53.4%), followed by liver (50.9%), prostate (45.9%), breast (43.6%), and colorectal (40.2%) cancers. Almost all SREs developed 1 month after bone metastasis, except in patients with breast and prostate cancers (median: 5.9 months in breast cancer and 4.7 months in prostate cancer). Survival duration after the development of bone metastasis was < 6 months in stomach, liver, colorectal, and lung cancer patients. Breast and prostate cancer patients survived for > 1 year after the occurrence of SREs. This study reveals the epidemiology of bone metastasis and SREs in Korean cancer patients, and the findings can be used to assess the actual bone health status of cancer patients.

A case of dwarfism in 6th century Italy: Bioarchaeological assessment of a hereditary disorder.

OBJECTIVE: The skeletal remains of a short-statured individual (T17) are described and a differential diagnosis performed to determine the etiology of the condition. MATERIALS: An individual considered pathologically short in stature was discovered in the burial site of Piazza XX Settembre, Modena (northern Italy). METHODS: Morphological and morphometric analyses were performed, and T17 was compared to dwarfs from other localities and periods and to the adult female population from the same site. A paleopathological survey was undertaken to assess the degree of the skeletal elements of T17 were affected. RESULTS: T17 was a female, 20-30 years of age at death, with a stature of 128 cm and disproportionate dwarfism associated with congenital skeletal dysplasia. CONCLUSIONS: T17 likely affected by a form of hypochondroplasia. SIGNIFICANCE: Anatomical consequences of hypochondroplasia are presented, and the timeframe and associated burial goods suggest a 6th-century Lombard short stature belonging to one of the earliest Lombard settlements in Italy. SUGGESTIONS FOR FURTHER RESEARCH: Future genetic analysis would resolve if the mutation in the type 3 fibroblast growth factor receptor (FGFR3) is present in the remains of T17; however, it is not exclusivly linked to hypochondroplasia.

Three-Dimensional Zero Echo Time Magnetic Resonance Imaging Versus 3-Dimensional Computed Tomography for Glenoid Bone Assessment.

PURPOSE: To evaluate the 3-dimensional (3D) zero echo time (ZTE) magnetic resonance imaging (MRI) technique and compare it with 3D computed tomography (CT) for the assessment of the glenoid bone. METHODS: ZTE MRI using multiple resolutions and multislice CT were performed in 6 shoulder specimens before and after creation of glenoid defects and in 10 glenohumeral instability patients. Two musculoskeletal radiologists independently generated 3D volume-rendered images of the glenoid en face. Post-processing times and glenoid widths were measured. Inter-modality and inter-rater agreement was assessed. RESULTS: Intraclass correlation coefficients (ICCs) for inter-modality assessment showed almost perfect agreement for both readers, ranging from 0.949 to 0.991 for the ex vivo study and from 0.955 to 0.987 for the in vivo patients. Excellent interobserver agreement was found for both the ex vivo (ICCs ≥ 0.98) and in vivo (ICCs ≥ 0.92) studies. For the ex vivo study, Bland-Altman analyses for CT versus MRI showed a mean difference of 0.6 to 1 mm at 1.0-mm3 MRI resolution, 0.3 to 0.6 mm at 0.8-mm3 MRI resolution, and 0.3 to 0.6 mm at 0.6-mm3 MRI resolution for both readers. For the in vivo study, Bland-Altman analyses for CT versus MRI showed a mean difference of 0.6 to 0.8 mm at 1.0-mm3 MRI resolution, 0.5 to 0.6 mm at 0.8-mm3 MRI resolution, and 0.4 to 0.8 mm at 0.7-mm3 MRI resolution for both readers. Mean post-processing times to generate 3D images of the glenoid ranged from 32 to 46 seconds for CT and from 33 to 64 seconds for ZTE MRI. CONCLUSIONS: Three-dimensional ZTE MRI can potentially be considered as a technique to determine glenoid width and can be readily incorporated into the clinical workflow. LEVEL OF EVIDENCE: Level II, development of diagnostic criteria (consecutive patients with consistently applied reference standard and blinding).

Assessment of heat generation and risk of thermal necrosis during bone burring by means of three-dimensional dynamic elastoplastic finite element modelling.

During bone burring, the heat generated due to friction at the bone-burr interface may cause thermal damage to the bone. Therefore, it is necessary to assess bone temperature distribution around a burring site and identify high-risk regions for thermal necrosis due to bone burring. In this study, a three-dimensional (3-D) dynamic elastoplastic finite element model for the burring process was developed and experimentally validated to investigate the influence of burring parameters (rotational speeds: 3,000, 10,000, 15,000 and 60,000 rpm; feed rates: 0.5, 0.9, 1.5 and 3.0 mm/s) on heat generation and evaluate the risk region for thermal necrosis. Calculated bone temperatures were compared with experimental values and found to be in good agreement with them. The analytical results demonstrated a linear relationship between the burring time and friction energy. In addition, the friction energy increased with the bone temperature. The high-risk thermal necrosis zone was measured from the edge of burring (y-direction) at feed rates of 0.5, 0.9, 1.5 and 3.0 mm/s and was found to be 7.8, 7.3, 6.6 and 5.5 mm, respectively. When the burr rotational speed increased from 3,000 to 60,000 rpm, the high-risk zone for thermal necrosis increased from 4.5 to 8.1 mm. We concluded that both the friction energy and the bone temperature increased in proportion with the burr rotational speed. Reducing burr rotational speeds and/or increasing feed rates may decrease the rise in bone temperature, thus decreasing the potential for thermal necrosis near the burring site. Our model can be used to select the optimal surgery parameters to minimise the risk of thermal necrosis due to bone burring and to assist in the design of optimal orthopaedic drill handpieces.

Updates in epidemiology, pathophysiology and management strategies of glucocorticoid-induced osteoporosis.

INTRODUCTION: Endogenous or exogenous (corticosteroid-induced) glucocorticoids (GCs) excess represents, together with diabetes, the most common cause of secondary osteoporosis. AREAS COVERED: We present a comprehensive overview about the pathophysiology, clinical management and treatment of GCs induced osteoporosis (GIOP). According to PRISMA guidelines, a literature search identifying articles about bone and GCs was done. EXPERT OPINION: Despite the progress over the years and the increase in therapeutic options, there still are controversial issues about the management of GIOP. These mainly include the failure of BMD or FRAX to completely account for the rapid increase in fracture risk of most GC-treated patients, the understanding about the independent contribution on bone fragility of the underlying disease requiring GCs therapy, and the necessity of clearer information about the anti-fracture efficacy and long term-safety of most therapeutic options. Moreover, there are no specific indications for the management of bone fragility in endogenous hypercortisolism. Notwithstanding the above limitations there is a general consensus to recommend an assessment of fracture risk in all individuals >40 years committed to receive (or continuing) high dose (>7.5 mg of prednisone equivalent) GCs for ≥3 months and in all patients with fragility fracture history.

A comparative assessment of consolidation materials applied to burned bone.

Fire-altered or fragmentary bone presents a challenge to forensic anthropologists and bioarchaeologists due to its characteristic friability. A potential solution to this problem is the use of consolidant materials on fragile osteological material, including burned remains. Although anthropologists and odontologists employ a variety of consolidant materials, there is no consensus regarding which material is most appropriate. Four easily obtained and commonly used consolidants, Acryloid™ B-72, Acrysol™ WS-24, Rhoplex™ B-60A, and Butvar® B-98, were compared to assess ease of material application and ability to stabilize burned bone. Each consolidant was applied to a subgroup of the study population at a 10% concentration. Total dry time per specimen, ease of solution preparation and application, and any alteration to the bone's appearance were recorded to assess the practical use of each material in field recovery settings. Nanoindentation, drop weight impact, and forced vibration tests were then performed to assess degree of stabilization. These tests were chosen to mimic possible real-world scenarios where burned bone may undergo damage during and after recovery, including repeated handling and transportation from the fire scene to the lab. Based on both qualitative and quantitative data collected, Acryloid™ B-72 is the most suitable consolidant tested to stabilize burned or fragmentary bone during recovery efforts. If the dry time for Rhoplex™ B-60A could be reduced by using a different solvent, such as acetone, Rhoplex™ B-60A would also be appropriate. Highly calcined areas, and targeted structures that could be utilized for positive identification, including teeth and the frontal sinus, should preferentially be consolidated with Acryloid™ B-72 in the field prior to recovery.

Role of cytotechnologists in rapid onsite adequacy assessment of cytology materials for diagnostic workup and specimen allocation for ancillary testing using a standardized protocol.

INTRODUCTION: Data on the performance of cytotechnologists in assessing specimen adequacy of needle core biopsies (NCB) is scant and their role in specimen triaging for ancillary studies have not been well established. MATERIALS AND METHODS: We retrospectively analyzed rapid onsite evaluation (ROSE) performed exclusively by cytotechnologists on 248 NCB and fine-needle aspiration (FNA) specimens. Overall adequacy and accuracy rates were determined by comparing to final diagnosis. We also reviewed the process of specimen allocation for ancillary testing to determine whether specimens were appropriately triaged at the time of ROSE. RESULTS: Of the 248 cases, 222 (89.5%) were touch imprint and 26 (10.5%) were FNA smears. The overall adequacy rate was 73.4% (182 of 248). Concordance for "adequate" interpretation by ROSE with unequivocal malignant or benign diagnoses on final interpretation was 95.6%. The sensitivity, specificity, and accuracy of ROSE for a final "positive for malignancy" were 89.2% (95% CI 83.04% to 93.69%), 43.24% (95% CI 31.77% to 55.28%), and 73.87% (95% CI 67.57% to 55.28%), respectively. Cases with "positive for malignancy" on final diagnosis were "adequate" by ROSE in 89.1% (132 of 148) and "inadequate" in 10.8% (16 of 148), P < 0.0001. Ancillary tests were performed in 168 of 248 (67.7%); the majority were immunohistochemical stains for determining tumor subtype. Predictive biomarkers were performed successfully in 100% of metastatic breast cancers. CONCLUSIONS: Cytotechnologists performed at a high level of competency in providing ROSE and allocating specimens for ancillary testing, which were performed successfully in the majority of cases. Implementation of a standardized protocol for tissue management/prioritization is of paramount importance to maximize tissue preservation and minimize wastage.

An investigative strategy for assessment of injuries in forensic anthropology.

In a forensic context, identification of skeletal injuries' and traumas' timing may be of fundamental relevance to understand the events related to the life and death of an individual. In this study, we propose a new evaluation form to facilitate the detection of traumas and interpret them as ante-, peri- or post-mortem injuries. We describe the use of this form with the analysis of two skeletonized individuals. Bone injuries on their skeletons were caused by diverse sharp weapons and differed for the timing they have occurred, as revealed by macroscopic, radiographic and microscopic assays. Thanks to its completeness and user-friendly approach, the evaluation form here proposed may greatly facilitate the analysis and interpretation of injuries found on skeletons under forensic investigation.

Hormone receptor and HER2 assessment in breast carcinoma metastatic to bone: A comparison between FNA cell blocks and decalcified core needle biopsies.

BACKGROUND: Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) guide the clinical management of breast cancer metastases. Decalcification of bone core needle biopsies (CNBs) can affect IHC. In the current study, the authors sought to define whether fine-needle aspiration (FNA) would be a better alternative to CNB for reliable IHC. METHODS: Patients with breast cancer metastases to bone that were sampled by both CNB and FNA were selected. ER, PR, and HER2 were performed in FNA cell blocks (FNA-CBs) and concurrent decalcified CNBs. Discrepancies were classified as minor when there was a difference of up to 30% nuclear staining in IHC for ER and PR between paired samples and as major when a clinically relevant change was observed (ie, positive vs negative). Quantitative reverse transcriptase-polymerase chain reaction of ESR1 messenger RNA levels was performed on FNA/CNB pairs with discrepancies for ER IHC. IHC status of the primary breast carcinoma was recorded. RESULTS: Concordance rates for ER, PR, and HER2 were 89%, 67%, and 93%, respectively, between FNA-CB and CNB pairs from 27 patients. Major discrepancies were noted in approximately 11% of FNA/CNB pairs for ER IHC and in 33% of FNA/CNB pairs for PR. ESR1 messenger RNA levels of FNA/CNB matched samples were similar and did not explain the differences in ER IHC expression in the majority of cases. Two of 27 FNA/CNB pairs had different results for HER2 IHC that changed from negative on CNB to equivocal (2+) on FNA-CB. Both cases had prior HER2 amplification by fluorescence in situ hybridization. CONCLUSIONS: FNA-CB and CNB appear to constitute acceptable methods for the assessment of ER, PR, and HER2 for clinical decision making.

Assessment of Bones Deficient in Fibrillin-1 Microfibrils Reveals Pronounced Sex Differences.

Defects in the extracellular matrix protein fibrillin-1 that perturb transforming growth factor beta (TGFß) bioavailability lead to Marfan syndrome (MFS). MFS is an autosomal-dominant disorder, which is associated with connective tissue and skeletal defects, among others. To date, it is unclear how biological sex impacts the structural and functional properties of bone in MFS. The aim of this study was to investigate the effects of sex on bone microarchitecture and mechanical properties in mice with deficient fibrillin-1, a model of human MFS. Bones of 11-week-old male and female Fbn1mgR/mgR mice were investigated. Three-dimensional micro-computed tomography of femora and vertebrae revealed a lower ratio of trabecular bone volume to tissue volume, reduced trabecular number and thickness, and greater trabecular separation in females vs. males. Three-point bending of femora revealed significantly lower post-yield displacement and work-to-fracture in females vs. males. Mechanistically, we found higher Smad2 and ERK1/2 phosphorylation in females vs. males, demonstrating a greater activation of TGFß signaling in females. In summary, the present findings show pronounced sex differences in the matrix and function of bones deficient in fibrillin-1 microfibrils. Consequently, sex-specific analysis of bone characteristics in patients with MFS may prove useful in improving the clinical management and life quality of these patients, through the development of sex-specific therapeutic approaches.

Quantitative Assessment of Bone Metastasis in Prostate Cancer Using Synthetic Magnetic Resonance Imaging.

OBJECTIVES: The aims of this study were to evaluate the feasibility of quantitative synthetic magnetic resonance imaging (SyMRI) for characterizing bone lesions in prostate cancer and to discriminate viable progressive osteoblastic bone metastasis from nonviable bone metastases with treatment-induced sclerosis during the treatment course. MATERIALS AND METHODS: This institutional review board-approved prospective study included 96 consecutive prostate cancer patients who underwent whole-body MRI including diffusion-weighted imaging at the time of staging at diagnosis or starting a new line of anticancer treatment. Additional synthetic MRI of the lumbosacral spine, pelvis, and proximal femurs was performed. A region of interest of 1.0 cm in diameter was set in each bone lesion by 2 independent readers who were blinded to bone lesions' diagnosis. Differences in SyMRI variables between the different bone lesions were compared with the Wilcoxon rank sum test, and associations of SyMRI variables with active disease were analyzed with logistic regression analysis. Performance of T1, T2, and proton density (PD) for diagnosing active disease was assessed using the area under the receiver operating characteristic curve. RESULTS: Ninety-three bone lesions were eligible for analysis. The PD values of active (viable) bone metastatic lesions were significantly higher than those of inactive (nonviable) bone metastatic lesions without sclerosis and those of red bone marrow (P < 0.001 for both readers). The PD values of inactive bone metastatic lesions with sclerosis were significantly lower than those of inactive bone metastatic lesions without sclerosis and red bone marrow (P < 0.001 for both readers). The PD value proved to be an independent significant indicator (P < 0.001) for differentiating bone lesions. The areas under the curve of T1/T2/PD for identifying active disease were 0.81/0.69/0.93 for reader 1 and 0.78/0.70/0.92 for reader 2, respectively. CONCLUSIONS: Signal quantification on SyMRI provides objective assessment of bone lesions in the lower trunk. The PD value can be useful to determine the viability of bone metastases in prostate cancer.

The intersections of industrialization: Variation in skeletal indicators of frailty by age, sex, and socioeconomic status in 18th- and 19th-century England.

OBJECTIVES: Intersectionality theory argues that various categories of identity and forms of systemic oppression interact and produce inequalities in resource access, economic opportunities, and health outcomes. However, there has been little explicit engagement with this theory by bioarchaeologists examining disparate health outcomes in the past. This study examines the associations among frailty, age at death, sex, and socioeconomic status (SES) in 18th- and 19th-century England. MATERIALS AND METHODS: The sample for this study comes from four industrial-era cemeteries from England, ca. 1711-1857. The associations among adult age (18+ years), SES, sex, and three skeletal indicators of stress (dental enamel hypoplasia [DEH, n = 293], cribra orbitalia [CO, n = 457], periosteal lesions [PNB, n = 436]) are examined using hierarchical log-linear analysis. RESULTS: Significant interactions existed among the variables examined for two skeletal indicators: high SES females had lower frequencies of CO relative to other groups and males between ages 30-45 years exhibited higher frequencies of PNB compared to females or males of older or younger ages, regardless of SES. Additionally, sex and SES were consistently associated with age at death. CONCLUSIONS: These results suggest that patterns of stress indicators cannot be examined solely across unilateral axes of age, SES, or sex. Intersecting axes of privilege, marginalization, and structural oppression may have buffered high SES females from some negative health outcomes (CO) while predisposing them to others (risk of maternal mortality). Likewise, the hazardous working conditions relegated to adult males may have heightened the risk of injury, infection, and death for middle-aged men in industrial-era England.

Distinguishing bone and soft tissue infections mimicking sarcomas requires multimodal multidisciplinary team assessment.

INTRODUCTION: The aims of this study were to report the presenting characteristics and identify how best to distinguish bone and soft-tissue infections that mimic sarcomas. MATERIALS AND METHODS: A total of 238 (211 osteomyelitis and 27 soft-tissue infections) patients referred to a tertiary sarcoma multidisciplinary team with suspected sarcoma who were ultimately diagnosed with a bone or soft tissue infection were included. Data from a prospectively collated database was analysed retrospectively. RESULTS: Of all possible bone and soft-tissue sarcoma referrals, a diagnosis of infection was made in 2.1% and 0.7%, respectively. Median age was 18 years in the osteomyelitis group and 46 years in the soft-tissue infection group. In the osteomyelitis group, the most common presenting features were pain (85.8%) and swelling (32.7%). In the soft-tissue infection group, the most common clinical features were swelling (96.3%) and pain (70.4%). Those in the soft-tissue group were more likely to have raised inflammatory markers. Radiological investigations were unable to discern between tumour or infection in 59.7% of osteomyelitis and 81.5% of soft-tissue infection cases. No organism was identified in 64.9% of those who had a percutaneous biopsy culture. CONCLUSIONS: This study has highlighted that infection is frequently clinically indistinguishable from sarcoma and remains a principle non-neoplastic differential diagnosis. When patients are investigated for suspected sarcoma, infections can be missed due to falsely negative radiological investigations and percutaneous biopsy. As no single clinical, biochemical or radiological feature or investigation can be relied upon for diagnosis, clinicians should have a low threshold for tissue biopsy and discussion in a sarcoma multidisciplinary team meeting.

Assessment of finite element models for prediction of osteoporotic fracture.

With increasing life expectancy and mortality rates, the burden of osteoporotic hip fractures is continually on an upward trend. In terms of prevention, there are several osteoporosis treatment strategies such as anti-resorptive drug treatments, which attempt to retard the rate of bone resorption, while promoting the rate of formation. With respect to prediction, several studies have provided insights into obtaining bone strength by non-invasive means through the application of FE analysis. However, what valuable information can we obtain from FE studies that have focused on osteoporosis research, with respect to the prediction of osteoporotic fractures? This paper aims to fine studies that have used FE analysis to predict fractures in the proximal femur through a systematic search of literature using PUBMED, with the main objective of supporting the diagnosis of osteoporosis. The focus of these FE studies is first discussed, and the methodological aspects are summarized, by mainly comparing and contrasting their meshing properties, material properties, and boundary conditions. The implications of these methodological differences in FE modelling processes and propositions with the aim of consolidating or minimalizing these differences are further discussed. We proved that studies need to start converging in terms of their input parameters to make the FE method applicable to clinical settings. This, in turn, will decrease the time needed for in vitro tests. Current advancements in FE analysis need to be consolidated before any further steps can be taken to implement engineering analysis into the clinical scenario.

Viable and necrotic tumor assessment from whole slide images of osteosarcoma using machine-learning and deep-learning models.

Pathological estimation of tumor necrosis after chemotherapy is essential for patients with osteosarcoma. This study reports the first fully automated tool to assess viable and necrotic tumor in osteosarcoma, employing advances in histopathology digitization and automated learning. We selected 40 digitized whole slide images representing the heterogeneity of osteosarcoma and chemotherapy response. With the goal of labeling the diverse regions of the digitized tissue into viable tumor, necrotic tumor, and non-tumor, we trained 13 machine-learning models and selected the top performing one (a Support Vector Machine) based on reported accuracy. We also developed a deep-learning architecture and trained it on the same data set. We computed the receiver-operator characteristic for discrimination of non-tumor from tumor followed by conditional discrimination of necrotic from viable tumor and found our models performing exceptionally well. We then used the trained models to identify regions of interest on image-tiles generated from test whole slide images. The classification output is visualized as a tumor-prediction map, displaying the extent of viable and necrotic tumor in the slide image. Thus, we lay the foundation for a complete tumor assessment pipeline from original histology images to tumor-prediction map generation. The proposed pipeline can also be adopted for other types of tumor.