Single Bone Research Articles

The morphological study of the pelvic guirdle and hind limbs of Jardina Roof rat (Rattus rattus)

The morphology of pelvic girdle and the hind limbs skeleton of Jardina roof rat were studied. The girdle has one pair of os-coxae, each os-coxae consisted of anterior-dorsal illium, posterior dorsal ischium and ventral posterior pubis. The construction of the bones is generally similar to other rodents. There were differences between the acetabulum, obturator, ischium and pubis of the jardina roof rat and African giant rat. The hind limbs are comprised of the single proximal bone, the femur and the distal paired bone, the tibia-fibula. The three trochanters of the femur were the same as other rats. The fibula was shorter than the tibia and separated proximally with a large interosseous space and fused with its distal third length to the tibia. The tarsals are the proximal bones that formed the ankle and the metatarsals are the distal bones that form the sole of the foot. The five metatarsals ended with three phalanges except the first one which has two phalanges. The fifth digit is characterized by an s-shaped phalanx.

A Case Report of Polyostotic form of Fibrous Dysplasia: Imaging Features in Radiograph, Computed Tomography and Magnetic Resonance Imaging

Fibrous dysplasia is a disease that causes aberrant development of osteoblasts, which results in fibrous stroma replacing normal bone. Lichtenstein first described it in 1938. It is a sporadic disorder caused due to a postzygotic mutation in the GNAS1 gene. It can affect a single bone (monostotic) or several bones (polyostotic). The most common locations are the skull & ribs. It is typically an incidental finding and asymptomatic. When a pathologic fracture or malignant alteration complicates it, symptoms could develop. As polyostotic FD is a rare disorder that only occasionally occurs in 20–25% of patients, therefore the aim of this article is to report such a rare case of polyostotic FD in a 30-year-old female patient showing the characteristic changes. Keywords: Polyostotic fibrous dysplasia, GNAS1 gene mutation, Sporadic disorder

Personalized loading conditions for homogenized finite element analysis of the distal sections of the radius

The microstructure of trabecular bone is known to adapt its morphology in response to mechanical loads for achieving a biomechanical homeostasis. Based on this form–function relationship, previous investigators either simulated the remodeling of bone to predict the resulting density and architecture for a specific loading or retraced physiological loading conditions from local density and architecture. The latter inverse approach includes quantifying bone morphology using computed tomography and calculating the relative importance of selected load cases by minimizing the fluctuation of a tissue loading level metric. Along this concept, the present study aims at identifying an optimal, personalized, multiaxial load case at the distal section of the human radius using in vivo HR-pQCT-based isotropic, homogenized finite element (hFE) analysis. The dataset consisted of HR-pQCT reconstructions of the 20 mm most distal section of 21 human fresh-frozen radii. We simulated six different unit canonical load cases (FX palmar–dorsal force, FY ulnar–radial force, FZ distal–proximal force, MX moment about palmar–dorsal, MY moment about ulnar–radial, MZ moment about distal–proximal) using a simplified and efficient hFE method based on a single isotropic bone phase. Once we used a homogeneous mean density (shape model) and once the original heterogeneous density distribution (shape + density model). Using an analytical formulation, we minimized the deviation of the resulting strain tensors ε(x) to a hydrostatic compressive reference strain ε0, once for the 6 degrees of freedom (DOF) optimal (OPT) load case and for all individual 1 DOF load cases (FX, FY, FZ, MX, MY, MZ). All seven load cases were then extended in the nonlinear regime using the scaled displacements of the linear load cases as loading boundary conditions (MAX). We then compared the load cases and models for their objective function (OF) values, the stored energies and their ultimate strength using a specific torsor norm. Both shape and shape + density linear-optimized OPT models were dominated by a positive force in the z-direction (FZ). Transversal force DOFs were close to zero and mean moment DOFs were different depending on the model type. The inclusion of density distribution increased the influence and changed direction of MX and MY, while MZ was small in both models. The OPT load case had 12–15% lower objective function (OF) values than the FZ load case, depending on the model. Stored energies at the optimum were consistently 142–178% higher for the OPT load case than for the FZ load case. Differences in the nonlinear response maximum torsor norm ‖t‖ were heterogeneous, but consistently higher for OPT_MAX than FZ_MAX. We presented the proof of concept of an optimization procedure to estimate patient-specific loading conditions for hFE methods. In contrast to similar models, we included canonical load cases in all six DOFs and used a strain metric that favors hydrostatic compression. Based on a biomechanical analysis of the distal joint surfaces at the radius, the estimated load directions are plausible. For our dataset, the resulting OPT load case is close to the standard axial compression boundary conditions, usually used in HR-pQCT-based FE analysis today. But even using the present simplified hFE model, the optimized linear six DOF load case achieves a more homogeneous tissue loading and can absorb more than twice the energy than the standard uniaxial load case. The ultimate strength calculated with a torsor norm was consistently higher for the 6-DOF nonlinear model (OPT_MAX) than for the 1-DOF nonlinear uniaxial model (FZ_MAX). Defining patient-specific boundary conditions may decrease angulation errors during CT measurements and improve repeatability as well as reproducibility of bone stiffness and strength estimated by HR-pQCT-based hFE analysis. These results encourage the extension of the present method to anisotropic hFE models and their application to repeatability data sets to test the hypothesis of reduced angulation errors during measurement.

A STUDY OF MINIMALLY INVASIVE PLATE OSTEOSYNTHESIS(MIPO) IN DISTAL TIBIAL METAPHYSEAL FRACTURE

Among all the fractures in the body, tibia is the single largest bone that is commonly involved in injuries. Owing to increase in vehicular accidents and industrial mishaps, high velocity trauma produces tibial fractures in increasing numbers. Fractures of distal tibia are critical because the tibial bone in lower end is subcutaneous with minimal muscle cover and with precarious blood supply, which makes fracture in this part of the tibia prone for many complications like wound dehiscence, infections, delayed union, malunion and ankle 1 stiffness following surgery or conservative management .

Abnormal DNA Damage Response Suggests Novel Fingerprint of Relapse in Acute Monocytic Leukemia Post Transplantation

Background The heterogeneity of acute myeloid leukemia plays an important role in the development of drug resistance. Minimal residual disease is the major cause of relapse for the patients who already received chemotherapy and stem cell transplantation. Some rare subgroups of leukemia cells harboring relapse-inducing genes were selected after chemotherapy. To unravel intra-tumoral heterogeneity and selective drug-resistance, single-cell RNA sequencing (scRNA-seq) was already performed on many solid tumors and blood cancer to achieve the high-resolution transcriptomic profiling on individual cells from a larger heterogeneous population. However, the mechanism underlying the reason of leukemia heterogeneity is still not validated. Methods Since single-cell suspension was obtained from bone marrow of acute myeloid leukemia samples, we used the 10x Genomics Chromium platform to capture transcriptomes of single cells on barcoded mRNA capture beads for massively parallel scRNA-seq. Data processing followed by Cell Ranger software pipeline to demultiplex cellular barcodes, and map reads to the genome and transcriptome hg38 using the STAR aligner. Unique molecular identifier (UMI) count matrix and quality control was performed using Seurat. The t-SNE map was calculated using Rtsne package. The related genes were overexpressed or knockdown in Thp1 cell line to investigate their roles in DNA damage response. Results We analyzed transcriptome data from above 50K single leukemia bone marrow cells across 3 patients during newly diagnosed, complete remission and relapse stages. These 3 patients belong to M4 or M5, according to French-American-British classification. The genotyping of them exhibited positive WT1-ABL, and negative for c-Kit, NPM1, FLT3-ITD and FL3-TKD. To define the landscape of cellular heterogeneity and its association with outcome in an unbiased manner, we performed unsupervised machine learning algorithm on near 50K single cells from leukemia bone marrow and identify one robust 14-cluster solution (from 0 to 13, Figure 1A) and the hallmark genes within each clusters (Figure 1B). The pattern exhibits distinct distribution on different stages (Figures 1C), indicating intra-tumoral heterogeneity during leukemia progression. The cluster 0 mainly contains newly diagnosed cells. Within cluster 0, several hallmark genes (Figure 2A), such as LILRB2(Leukocyte immunoglobulin like receptor 2) and TNFAIP2(TNF alpha induced protein 2) were already reported to be associated with AML. Interestingly, the subpopulation of PTAFR (Platelet-activating factor receptor) highly expressing cells were identified in newly diagnosed group, though whether PTAFR can induce acute myeloid leukemia is still elusive. Cells expressing these genes rarely occur at relapse region (Figure 1C), implying that these genes may be not related to relapse. However, cells expressing genes, such as RPS4Y1(Ribosomal protein S4, Y isoform 1), CDKN2A, KLF1 or GATA1 were mainly distributed in relapse group, and rare cells can be found in newly diagnosed group, implying that these genes may have potential role in chemotherapy resistance, and subclones expressing these genes expanded during leukemia progression. The high expression of KLF1 as erythropoietic transcription factor and GATA1 was associated with AML. Higher levels of GATA1 expression had poor outcomes. Next, we found these genes were associated with abnormal DNA damage response, which contributes to leukemia heterogeneity. These genes can regulate the pathway of DNA damage repair as the switch between NHEJ (Non-Homologous End Joining) and HR (Homologous recombination). Conclusion The application of scRNA-seq in cancer has been relatively limited in patients who achieve remission and appear relapse after therapy. We analyze heterogeneity of acute myeloid leukemia during progression and identify novel relapse subgroups in these heterogeneous populations. Our results show a greater degree of heterogeneity in AML tumor samples during leukemia progression, compared to traditional bulk RNA-seq, and highlights the potential of single-cell RNA-seq to identify novel subgroups in AML related to relapse, demonstrating the value of single-cell analysis for AML. Furthermore, we illustrate the roles of relapse-related genes in regulating DNA damage response, which facilitate better understanding of leukemia heterogeneity.

Spatial Organization of Hematopoietic Clones in the Bone Marrow of a Patient with Polycythemia Vera

All humans become genetic mosaics over time as our stem cells acquire somatic mutations throughout life. In the hematopoietic compartment, this phenomenon is termed clonal hematopoiesis (Steensma et al. 2015). Clonal hematopoiesis (CH) increases in prevalence with age and is associated with an increased risk for hematologic malignancy (Genovese et al. 2014; Jaiswal et al. 2014; Xie et al. 2014). CH harboring JAK2 mutations are frequently observed in healthy individuals; and yet JAK2 mutations are also the most frequent drivers of myeloproliferative neoplasms (MPNs) such as polycythemia vera (PV). MPNs are clonal diseases marked by dysregulated hematopoiesis and can progress to a secondary myelodysplastic syndrome or acute leukemia. There is increasing evidence that the clonal mutations driving MPNs arise early in life-potentially in utero-often years before the development of symptoms (Williams et al. 2022). While the intrinsic factors driving clonal expansion are increasingly known (Watson et al. 2020), the extrinsic factors driving the expansion of clones harboring these MPN driver mutations are not well characterized. Prior work has shown that clonal mutations are geographically constrained in solid organs such as skin, colon and esophagus (Lee-Six et al. 2018; Martincorena et al. 2015, 2018). Strikingly, in the esophagus non-malignant NOTCH1 mutant clones can even outcompete nascent malignant clones (Colom et al. 2021). In the hematopoietic compartment, the spatial organization of clones harboring these mutations and their interaction with the niche and each other is largely unknown. We hypothesized that clonal mutations are geographically constrained in the bone marrow niche as is seen in solid organs. To answer these questions, we developed methods for spatially-aware clonal mutation detection. As proof of principle, we characterized the hematopoietic clonal organization within a femur head explant from a 50 year-old man with PV undergoing hip arthroplasty. Briefly, the femur head was sectioned into 2mm slices, which were then further partitioned into approximately 300 bone marrow fragments (2mm3). Approximately 20% of the fragments were snap frozen and pulverized for DNA extraction. The remainder were formalin fixed and decalcified for correlative imaging. Targeted error-corrected sequencing was performed using a myeloid-specific panel (Duncavage et al. 2018) on 24 bone marrow fragments, and bulk peripheral blood and bone marrow aspirate. In the peripheral blood, JAK2 V617F (0.24 VAF) and TET2 L1081* (0.02 VAF) mutations were identified. In the bone marrow aspirate, the same JAK2 (0.62 VAF) and TET2 (0.05 VAF) mutations were identified in addition to a DNMT3A R882C mutation (0.02 VAF). Interestingly, peripheral blood sequencing two years prior identified the JAK2 and DNMT3A mutations, but not the TET2 mutation, suggesting recent clonal expansion of TET2 mutant clone. From the 24 sequenced bone marrow fragments, the geographical organization of clonal mutations in the bone marrow was determined (Figure 1). The JAK2 V617F clone was identified in all bone marrow fragments sequenced (0.12-0.69 VAF). The TET2 L1081* clone was identified in 11/24 bone marrow fragments with some regional constraint (0.03-0.05 VAF). The DNMT3A R882C mutation was detected in only a single bone marrow fragment (0.02 VAF) and co-localized with the JAK2 V617F and TET2 L1081* mutations. A previously undetected clonal SETBP1 E616V mutation was identified in two adjacent bone marrow fragments from sequential slices of the femur head (0.05 VAF and 0.10 VAF). Together this provides the first characterization of spatial organization of clonal mutations in the bone marrow niche for an MPN patient. Currently, we are utilizing digital droplet PCR targeting these detected mutations in ~60 additional bone marrow fragments to accurately quantify clone size across the tissue. We plan to employ multiplex fluorescent imaging of bone marrow fragments adjacent to detected clusters of mutations to identify the surrounding bone marrow niche elements in those regions. These findings suggest that bone marrow biopsy from a small section of bone marrow may not accurately describe disease state and clonal mutation burden in myeloid neoplasms. Future applications of these tools will help describe the extrinsic factors and local microenvironment that drive clonal evolution over time in the bone marrow. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Polyostotic DLBCL Is Characterized By a NF-Κb Pathway Affecting Molecular Profile and Superior Survival

Introduction Polyostotic diffuse large B-cell lymphoma (DLBCL) is a rare extranodal disease with only multifocal bone localizations that has not extensively been studied. Other known bone DLBCL comprises primary bone (PB-)DLBCL with a single bone localization with(out) locoregional lymphadenopathy and disseminated-DLBCL with ≥1 bone lesion(s) and ≥1 (extra) nodal localization(s). Recently (PMID: 34478526, de Groen et al.), we demonstrated a germinal center B-cell (GCB)-subtype with a centrocyte-like phenotype and a unique corresponding molecular profile, reflecting favorable prognosis for PB-DLBCL compared to non-bone DLBCL with a GCB-subtype. Here, the molecular characteristics of polyostotic-DLBCL were assessed and compared to PB-DLBCL, disseminated-DLBCL, and nodal DLBCL-GCB, using an extensive targeted next-generation sequencing (tNGS) panel. Methods This retrospective multicenter study analyzed 14 polyostotic-DLBCL, 44 PB-DLBCL, 26 disseminated-DLBCL, and 36 nodal DLBCL-GCB cases (selection based on PET/CT-scan), including well-annotated histological and clinical data. Cases were diagnosed with immunohistochemistry following the revised WHO classification of 2016. Cell-of-origin (COO) was determined by Hans' algorithm. Presence of MYC/BCL2/BCL6-rearrangements were identified through fluorescent in situ hybridization (FISH) and break-apart probes. High-grade B-cell lymphomas (double/triple hit) were excluded. As described (PMID: 34478526), tNGS was performed, using an extended panel consisting of 128 (LYMFv2, mostly used) or 52 (LYMFv1) B-cell lymphoma relevant genes. Results Our cohort consisted of 120 patients (78 males, 65%) with a median age at diagnosis of 61 (range 13-91). Half of the polyostotic-DLBCL cases belonged to a GCB phenotype (8/14, 57%), while a GCB phenotype was more frequently identified in PB-DLBCL (31/44, 70%) and disseminated-DLBCL (18/26, 69%). Using tNGS with LYMFv2 and LYMFv1, respectively 57 and 36 cases were successfully analyzed, elucidating (in)activating pathogenic mutations in 124 different genes. In polyostotic-DLBCL, frequent mutations in f.e.CARD11 and MYD88 demonstrated a unique mutational profile affecting the NF-κB pathway characteristic of ABC-genotypes (Figure 1, P=0.018), compared to PB-DLBCL, disseminated-DLBCL and nodal DLBCL-GCB. In contrast, an exclusive immunomodulatory profile with frequent mutations in B2M, IRF8 and TNFRSF14 was identified for PB-DLBCL (P=0.029). Focusing on GCB-associated epigenetic genes (CREBBP, EP300, EZH2, KMT2D, etc.), no significant difference was found between the mentioned DLBCL subgroups. Mutational profiles of disseminated-DLBCL revealed a broad spectrum of abnormalities (BCL2, CREBBP, TNFRSF14, and TP53), partially consistent with either an immunomodulatory or an epigenic genotype. Nodal DLBCL-GCB was specifically characterized by frequent aberrations in BCL2 and MYC and lacked an immunomodulatory or NF-κB activating genotype. Given >1 extranodal localizations, polyostotic-DLBCL is classified as high-risk disease with Ann Arbor stage IV. Compared to disseminated-DLBCL with similar stage III/IV disease, polyostotic-DLBCL demonstrated a superior 3-year overall survival (Figure 2, log-rank, p<0.001, HR: 4.76, CI: 1.4-15.9). Conclusion Polyostotic-DLBCL showed a unique mutational profile with frequent NF-κB-activating mutations, in contrast to PB-DLBCL, disseminated-DLBCL and nodal DLBCL-GCB. Despite this ABC-associated profile of polyostotic-DLBCL and its high Ann Arbor stage, a favorable prognosis was identified especially compared to similar high Ann Abor stage disseminated-DLBCL. To study COO and tumor microenvironment in more detail to evaluate polyostotic-DLBCL as a separate biological disease entity, gene-expression profiling with the BLYM777 panel (PMID: 35454765) will be presented at the meeting. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Overcoming the chaotic numerology of osteometry. A proposal for a univocal numeric coding system for osteometric measurements of the human skeleton

Osteometric measurements have a critical role particularly in forensic anthropology. They allow the objective quantification of morphological characteristics when developing the biological profile of unknown skeletons, rather than relying purely on qualitativedescriptions that are often subjective. Various coding systems for anthropometric measurements have been developed across the years and countries. Currently, there is not a shared classification for the most commonly applied measurements in osteometry. For ascientific community becoming ever more global and international, the lack of a common language can create impasses and lead to miscommunications between scientists. The problem could become more relevant in mass fatalities and international scenarios. In order to develop a new communal codification model, some imperfections in traditional classifications have been identified and overcome. The new proposed coding is based on a three-number taxonomy. The three cyphers, separated by a dot (#.#.#), indicate the anatomical area of which the measurement is referred (e.g. cranium, upper limb), the single bone (e.g. humerus) or the topographicregion (e.g. neurocranium) measured, and the specific measurement. The third number, an arithmetic progression that identifies every measurement, has been designed to allow the scientific community to introduce new measurements without scrambling the entire series

LANGERHANS CELL HISTIOCYTOSIS IN A CHILD WITH ALBINISM AND INVASIVE SKULL LESIONS

<h3>Introduction</h3> Langerhans cell histiocytosis (LCH) is a rare disorder that involves excess production of dendritic cells, a form of histiocyte. LCH is heterogeneous in its presentation, varying from single bone lesions to multi-organ failure and considerable mortality. Here, we present a child with LCH who has albinism and persistent skull and orbital lesions. <h3>Case Description</h3> Patient from rural Guatemala was seen at the National Public Hospital of Escuintla during a medical mission trip. He was a 2-year-old boy with congenital albinism and a 6-month history of ulcerative lesions of the right periorbital, frontal, and retroauricular areas with purulent and malodorous discharge (Figure 1A,B). Lesions continued to worsen despite two courses of unknown oral antibiotics and chlorine dioxide rinses. Birth history was unremarkable; he received routine vaccinations including BCG. Skull x-ray showed a large area of decreased lucency in the right frontal and parietal lobe (Figure 1C). MRI of brain and orbits revealed a necrotic mass in the same area (Figure 1D). Wound cultures grew <i>Pseudomonas aeruginosa</i> and intravenous cefepime was initiated. Patient was transferred to the main cancer institute in Guatemala where biopsy of the skull lesion confirmed LCH. <h3>Discussion</h3> The diagnosis of LCH in our case was delayed primarily due to the limited resources and access to medical care. LCH can be invasive, and patients often need a multidisciplinary team approach in a tertiary care center. Additional immunologic studies and genetic evaluation, if available, can provide further insights. To our knowledge, this is the first report of LCH in a patient with albinism.

Clinical and functional evaluation of bone marrow aspirate concentrate vs autologous conditioned serum in the treatment of knee osteoarthritis.

The aim of this study was to compare the efficacy of a single Bone Marrow Aspirate Concentrate (BMAC) with a cycle of 4 Autologous Conditioned Serum (ACS) injections in the treatment of early-stage knee osteoarthritis (OA). Two groups of 12 patients with degenerative knee OA were treated with a single BMAC injection and with a cycle of 4 ACS injections respectively. Follow-up was set at baseline (t0), one-month (t1) and six-months (t2) evaluating VAS for pain, WOMAC index and range of motion (ROM). We reported a significant improvement in WOMAC after BMAC injection both at t1 (p= 0,001) as well as t2 (p< 0,001), plus a reduction of VAS values in BMAC group at six months follow-up (p = 0,024). In contrast, no significant differences in ROM between the two groups were observed. Both the approaches are safe and effective in the treatment of knee OA, with a major efficacy of BMAC.

Incidence Of Tibial Diaphyseal Fractures Among Patients Presenting With Motorcycle Accidents.

To determine the frequency of tibial diaphyseal fractures among patients presenting with motorcycle accidents. It was a cross-Sectional Study, conducted at Department of Orthopaedic Surgery, Jinnah Postgraduate Medical Centre (JPMC), Karachi between May to December, 2020. All patients irrespective of gender, between ages 18-60 years who suffered from a motorcycle injury with a single bone involvement were eligible for the study. All patients who refused to take part in the study, had head injury, or had multiple fractures were excluded from the study. The data included patient's age, sex, associated bones involved and types of injury. The fractures were classified according to whether it was open or closed. A total of 174 patients were included in the study with a mean±SD age of 43.7±12.4. Tibial diaphyseal fracture was found to be in 111 (63.8%) patients as shown. Duration of fracture, gender, side of fracture, type of fracture was done with respect to Tibial diaphyseal fracture among patients. Insignificant difference was noted in age group (p=0.346), duration of fracture (p=0.087), gender (p=0.672), and type of fracture (p=0.063) whereas significant difference was found in side of fracture (p=0.0001). We highlighted the importance of tibial diaphyseal fractures in middle aged men who use motorcycles as a means of transport in Karachi, Sindh which is a frequent finding among these patients. Efforts should be made at both the community and government levels to increase awareness regarding traffic rules and consequences of reckless driving.

Metatarsal fusion resisted bending as jerboas (Dipodidae) transitioned from quadrupedal to bipedal.

Hind limbs undergo dramatic changes in loading conditions during the transition from quadrupedal to bipedal locomotion. For example, the most early diverging bipedal jerboas (Rodentia: Dipodidae) are some of the smallest mammals in the world, with body masses that range between 2–4 g. The larger jerboa species exhibit developmental and evolutionary fusion of the central three metatarsals into a single cannon bone. We hypothesize that small body size and metatarsal fusion are mechanisms to maintain the safety factor of the hind limb bones despite the higher ground reaction forces associated with bipedal locomotion. Using finite-element analysis to model collisions between the substrate and the metatarsals, we found that body size reduction was insufficient to reduce bone stress on unfused metatarsals, based on the scaled dynamics of larger jerboas, and that fused bones developed lower stresses than unfused bones when all metatarsals are scaled to the same size and loading conditions. Based on these results, we conclude that fusion reinforces larger jerboa metatarsals against high ground reaction forces. Because smaller jerboas with unfused metatarsals develop higher peak stresses in response to loading conditions scaled from larger jerboas, we hypothesize that smaller jerboas use alternative dynamics of bipedal locomotion to reduce the impact of collisions between the foot and substrate.

Mortality from fall: A descriptive analysis of a multicenter Indian trauma registry

IntroductionFall is the second most common mechanism of trauma worldwide after road traffic injuries. Data on fall predominantly comes from the high-income countries (HICs) and mostly includes injuries in children and elderly. There are very few studies from low- and middle-income countries(LMICs) that describe fall related injuries other than fragility fractures in elderly. This study describes the profile of poly-trauma patients admitted with a history of ‘fall’ and assesses the variables associated with mortality. MethodWe analyzed data from the ‘Towards Improved Trauma Care Outcome’ (TITCO) database which prospectively collected data of poly-trauma patients admitted to four major tertiary care hospitals of India between 2013 to 2015. Patients across all age groups admitted to hospital with the history of ‘fall’; were included in our study. Single bone fractures were excluded. The Kaplan Meier survival analysis was used to estimate the survival probability in different age groups. ResultsA total of 3686 patients were included in our study. The median age of the patients was 28 years (IQR: 9, 47) with the majority being males (73.6%). Almost one-third of the patients were within the age group of 0-14 (30.4%). Most of the patients (79.9%) had a diagnosis of traumatic brain injury (TBI). The overall in-hospital mortality was 18% (664), but higher at 39.0% among patients over 65 years of age. Probability of survival decreased with increase of age. ConclusionFalling from height is a common injury mechanism in India, occurring more in young males and usually associated with TBI. Isolated TBI and TBI associated with other injuries are the main contributors of mortality in fall injuries. Mortality from these injuries increased with age and ISS.

Taxonomic classification of seabird long bones using 3D shape: A method with wider potential in zooarchaeology

Identifications from isolated bones using molecular methods are not always possible (e.g. fossils and older sub-fossils), and specialist taxonomic expertise is not always available. Shape-based, geometric morphometric methods for identifying taxa from a single bone can provide a potential solution for faunal studies requiring taxonomic information about isolated bones. We present a generalisable method for taxonomic classification using 3D shape analyses combined with partial least squares discriminant analysis (PLSDA). Our classification protocol uses both well-established landmark-based techniques and novel landmark-free (i.e. pseudolandmark-based) shape analysis methods. Landmark-free methods can improve the automation of the classification method. We demonstrate with three case studies that 3D shape-based PLSDA can accurately predict taxonomic identities for seabird long bones to at least family-level. Landmark-based PLSDA assigned femora from penguins and tubenosed birds to the correct order and family with 100% accuracy, sensitivity and specificity. Pseudolandmark-based PLSDA assigned humeri from penguins and tubenosed birds to the correct family with 100% accuracy, sensitivity and specificity. Our 3D shape-based classification method could reliably contribute to the identification of bone remains when only isolated or typically nondiagnostic bones (i.e. elements with comparatively little variation in discrete character states or measurement proportions when comparing between closely-related taxa) are available, and when molecular methods are not possible or feasible. We provide a framework for applying this method to 1) much larger datasets which may allow finer-level classifications (genus or species), and 2) groups beyond seabirds.

Characteristics and survival in bone metastatic breast cancer patients with different hormone receptor status: A population-based cohort study.

BackgroundAccumulating preclinical evidence has uncovered the indispensable role of steroid hormone and their receptors, namely, estrogen receptor (ER) and progesterone receptor (PR), in the development of bone metastases in breast cancer. Limited data are available regarding the survival difference between different hormone receptor (HR) subgroups, and its prognostic significance is uncertain now. Such data are important for risk stratification and needed to formulate specialized regimen for bone metastatic breast cancer.MethodsFrom the year of diagnosis 2010 to 2018, 554,585 breast cancer patients, among which are 19,439 with bone metastasis and 10,447 with bone-only metastasis, were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan–Meier survival analysis was performed to compare the survival difference between the different HR status subgroups. Univariate and multivariate Cox proportional hazard regression was used to validate the prognostic role of HR status and identify other prognostic factors in bone metastatic breast cancer.ResultsER-positive/PR-positive breast cancer patients with bone metastasis showed the best breast cancer-specific survival (BCSS) and overall survival (OS) than those with other HR statuses, while single PR-positive bone metastatic breast cancers manifest similar survival with ER-negative/PR-negative ones. Adjusted Cox regression analysis demonstrated that patients with older age, male, black race, ILC, higher tumor grade, T3–T4, HER2-negative status, absence of surgery or adjuvant treatment, and HR status other than ER-positive/PR-positive tended to have worse outcomes. Further subgroup analysis based on HER2 status showed that within HER2-positive breast cancers, ER-positive/PR-positive ones still manifest better survival than the other three HR status subgroups, which are similar in survival outcomes.ConclusionAlthough collectively viewed as HR-positive breast cancers, certain distinctions exist between bone metastatic breast cancers with different HR statuses in survival outcome. Our findings indicate that despite metastasizing to the same location, the different survival rate is determined by the HR status of breast cancer. The selection and intensity of the regimen should consider HR status, and HER2 status occasionally, when treating bone metastatic breast cancer.

Multi-scale numerical simulation on mechano-transduction of osteocytes in different gravity fields

A three-dimensional model for osteocyte was established to research the mechanisms of mechano-transduction and amplification of primary cilium and osteocyte process in every gravity field. The results showed that significant stress concentration was observed in the area of physical connection between TES and the osteocyte process, where the fluid shear stress (FSS) was around two orders of magnitude higher than that in other areas. Due to the significant amplification effect of the TES structure on mechanical stimulation, making osteocyte process the “optimal mechanical receptor”. In microgravity, the mechanical signal conduction ability of the osteocyte decreased significantly.. Highlights At the micro-nano scale, a 3D model for single bone lacunae-osteocyte system is established. The stress amplification mechanism of the transverse element is verified. Compared with the primary cilium, osteocyte process is the ‘optimal mechanical receptor’. In microgravity, the mechanical signal conduction ability of osteocyte system decreased.

"False" foramina and fissures of the skull: a narrative review with clinical implications.

"False" foramina and fissures of the skull are described as openings formed between the adjacent edges of two or more bones and not conduits directly through a single bone. Trauma and metabolic disorders appear to affect these foramina and fissures differently when compared to the "true" foramina and fissures. Therefore, the aim of this paper is to provide a narrative review of the current literature about "false" foramina and fissures of the skull and skull base with a focus on their clinical significance.

Developmental osteology of Ictalurus punctatus and Noturus gyrinus (Siluriformes: Ictaluridae) with a discussion of siluriform bone homologies

Abstract The skeleton of Siluriformes is characterized by several autapomorphies, including secondary absence, extreme modification, and purported fusion of several ossifications. Although well documented in adults, information on skeletal development in catfishes is relatively sparse and typically focused on particular regions of the skeleton (e.g., Weberian apparatus). To further our understanding of the siluriform skeleton, I document the development of the entire skeleton in two ictalurid species, Ictalurus punctatus (channel catfish) and Noturus gyrinus (tadpole madtom) from five days pre-hatch to adult. I reexamine the homologies of bones previously hypothesized to represent compound elements in catfishes as well as an additional element only known to occur in some ictalurids. Development of the skeleton is complete in I. punctatus at 22.4 mm SL and almost complete in N. gyrinus (except dorsal- and anal-fin distal radials) at 14.1 mm SL. No signs of ontogenetic fusion were observed in any of the purported compound elements. Previous hypotheses of the homology of these elements and of additional ossifications are reviewed in light of developmental information obtained herein. No dermal parietal component is present at any stage in the so-called parieto-supraoccipital. The bone is the supraoccipital which ossifies from two lateral centers of ossification which later fuse, rather than from a median center. The ‘posttemporo-supracleithrum’ originates from a single center of ossification and represents the supracleithrum. The posttemporal is present in ictalurids and many other catfishes as a canal-bearing bone between the supracleithrum and the pterotic, a bone sometimes identified as the extrascapular. The extrascapular is missing in catfishes. Ictalurids have an additional dermal bone above the posttemporal, which is either an independently ossifying fragment of the posttemporal or a neoformation restricted to some members of this family. The single chondral bone of the pectoral girdle originates from a single center of ossification that represents the coracoid. The scapula is missing in catfishes. Dorsal-fin distal radial 2 is absent in catfishes and the foramen of dorsal-fin spine 2 is formed from modifications to the base of the fin-ray itself. Unlike loricarioid catfishes, the urohyal of ictalurids originates solely as an ossification of the sternohyoideus tendons. The anteriormost infraorbital element ossifies from a single center of ossification around the infraorbital sensory canal and represents the lacrimal. The antorbital is missing in catfishes. Finally, skeletal development of I. punctatus is compared to that available for other otophysans, including the cypriniforms Danio rerio and Enteromius holotaenia and the characiform Salminus brasiliensis.

Knee osteochondritis dissecans-treatment technical aspects

Purpose and objectiveCurrent treatments of different stages of knee osteochondritis Dissecans (OCD) are depending on the age of the patients and the stability of the diseased osteochondral area. The purpose of this paper was to summarize the treatment alternatives in order to simplify the choice for the treating surgeon. Background and principle resultsOsteochondritis dissecans (OCD) of the knee is an idiopathic and local osteochondral abnormality that affects mainly children and adolescents with risk of loosening of osteochondral fragments. A good clinical result can be expected when the physes are still open, when the osteochondritis is small and when the osteochondritis can be assessed as stable by MRI. Unstable OCD lesions most often need to be treated operatively by different fixation methods and when the osteochondral cannot be refixated, different local chondral and osteochondral repairs are available to fill up the defect area to congruity Summary and major conclusionsThe final choice of which treatment to use is depending on fragment viability and forms. Viable fragments are refixated while poor quality fragments are removed followed by a local biological osteochondral repair. Such osteochondral resurfacing may be single bone marrow stimulation with or without scaffold augmentation or different cell seeded grafts.

Characterization of Traumatic Injuries Due to Motor Vehicle Collisions in Neotropical Wild Mammals

Motor vehicle collisions (MVCs) are a severe threat to wildlife biodiversity worldwide and most vertebrate species are at risk. However, there is a considerable knowledge gap on the traumatic features and potential patterns of MVCs in wildlife. We investigated traumatic injuries (TIs) caused by MVCs (MVCs-TIs) in 430 neotropical wild mammals representing 44 species from Brazil. Injuries were classified topographically into four categories: abdomen/pelvis (AP), chest (TX), head/neck (HN) and extremities (EX). We also determined the prevalence of pathological changes in MVC fatalities. AP (n=381; 89%) was the most affected body segment, followed by TX (n=372; 87%), HN (n=363; 84%) and EX (n=288; 67%). The most prevalent gross pathological findings were single or multiple bone fractures (n=397; 92%), visceral organ rupture (n=371; 86%), haemothorax (n=220; 51%) and pulmonary haemorrhage (n=212; 49%). Microscopically, pulmonary oedema (n=324; 82%) and haemorrhage (n=272; 69%) were the most prevalent lesions. No distinct TI patterns were evident across the various taxonomic groups, although trends were found in some taxa, such as armadillos. These results may help clinicians performing emergency care on MVC wildlife patients and may be of value in pathological and forensic investigations where a MVC has been deemed a likely contributory factor to death.