There is controversy regarding the effect of different
Renal Osteodystrophy is a type of metabolic bone disease characterized by bone mineralization deficiency due to electrolyte and endocrine abnormalities. Patients with chronic kidney disease (CKD) are more likely to experience falls and fractures due to renal osteodystrophy and the high prevalence of risk factors for falls. Treatment involves medical management to resolve the etiology of the underlying renal condition, as well as management (and prevention) of pathological fractures. A 66-year-old female patient, with severe osteoporosis and chronic kidney disease undergoing haemodialysis, has presented with multiple fractures along the years. She was submitted to bilateral proximal femoral nailing as fracture treatment on the left and prophylactically due to pathological bone injury on the right, followed by revision of the left nail with a longer one after varus angulation and fracture distal to the nail extremity. Meanwhile, the patient suffered a pathological fracture of the radial and cubital diaphysis and was submitted to conservative treatment with cast, with consolidation of the fracture. Posteriorly, she re-fractured these bones after a fall and repeated the conservative treatment. Clinical management: There is a multidisciplinary
Open limb fractures are typically due to a high energy trauma. Several recent studied have showed treatment's superiority when a multidisciplinary
In this work, we propose a new quantitative way of evaluating acute compartment syndrome (ACS) by dynamic mechanical assessment of soft tissue changes. First, we have developed an animal model of ACS to replicate the physiological changes during the condition. Secondly, we have developed a mechanical assessment tool for quantitative pre-clinical assessment of ACS. Our hand-held indentation device provides an accurate method for investigations into the local dynamic mechanical properties of soft tissue and for in-situ non-invasive assessment and monitoring of ACS. Our compartment syndrome model was developed on the cranial tibial and the peroneus tertius muscles of a pig's leg (postmortem). The compartment syndrome pressure values were obtained by injecting blood from the bone through the muscle. To enable ACS assessment by a hand-held indentation device we combined three main components: a load cell, a linear actuator and a 3-axis accelerometer. Dynamic tests were performed at a frequency of 0.5 Hz and by applying an amplitude of 0.5 mm. Another method used to observe the differences in the mechanical properties inside the leg was a 3D Digital Image Correlation (3D-DIC). Videos were taken from two different positions of the pig's leg at different pressure values: 0 mmHg, 15 mmHg and 40 mmHg. Two strains along the x axis (Exx) and y axis (Eyy) were measured. Between the two pressure cases (15 mmHg and 40 mmHg) a clear deformation of the model is visible. In fact, the bigger the pressure, the more visible the increase in strain is. In our animal model, local muscle pressures reached values higher than 40 mmHg, which correlate with observed human physiology in ACS. In our presentation we will share our dynamic indentation results on this model to demonstrate the sensitivity of our measurement techniques. Compartment syndrome is recognised as needing improved clinical management tools. Our
Recent National Institute for Health and Care Excellence (NICE) guidance has advised against the continued use of the Thompson implant when performing hip hemiarthroplasty and recommended surgeons consider using the anterolateral surgical approach over a posterior
In osteoarthritis, chondrocytes acquire a hypertrophic phenotype that contributes to matrix degradation. Inflammation is proposed as trigger for the shift to a hypertrophic phenotype. Using in vitro culture of human chondrocytes and cartilage explants we could not find evidence for a role of inflammatory signalling activation. We found, however, that tissue repair macrophages may contribute to the onset of hypertrophy (doi: 10.1177/19476035211021907) Intra-articularly injected triamcinolone acetonide to inhibit inflammation in a murine model of collagenase-induced osteoarthritis, increased synovial macrophage numbers and osteophytosis, confirming the role of macrophages in chondrocyte hypertrophy occurring in osteophyte formation (doi: 10.1111/bph.15780). In search of targets to inhibit chondrocyte hypertrophy, we combined existing microarray data of different cartilage layers of murine growth plate and murine articular cartilage after induction of collagenase-induced osteoarthritis. We identified common differentially expressed genes and selected those known to be associated to inflammation. This revealed EPHA2, a tyrosine kinase receptor, as a new target. Using in silico, in vitro and in vivo models we demonstrated that inhibition of EPHA2 might be a promising treatment for osteoarthritis. Recently, single cell RNA-seq. has revealed detailed information about different populations of chondrocytes in articular cartilage during osteoarthritis. We re-analysed a published scRNA-seq data set of healthy and osteoarthritic cartilage to obtain the differentially expressed genes in the population of hypertrophic chondrocytes compared to the other chondrocytes, applied pathway analyses and then used drug databases to search for upstream inhibitors of these pathways. This drug repurposing
Low back pain affects 80% of the population with half of cases attributed to intervertebral disc (IVD) degeneration. However, the majority of treatments focus on pain management, with none targeting the underlying pathophysiological causes. PCRX-201 presents a novel gene therapy
Abstract. The lateral ligaments of the ankle composed of the anterior talofibular (ATFL), calcaneofibular (CFL) and posterior talofibular ligaments (PTFL), are amongst the most commonly injured ligaments of the human body. Although treatment methods have been explored exhaustively, healing outcomes remain poor with high rates of re-injury, chronic ankle instability and pain persisting. The introduction and application of tissue engineering methods may target poor healing outcomes and eliminate long-term complications, improving the overall quality of life of affected individuals. For any surgical procedure or tissue-engineered replacement to be successful, a comprehensive understanding of the complete anatomy of the native structure is essential. Knowledge of the dimensions of ligament footprints is vitally important for surgeons as it guides the placement of bone tunnels during repair. It is also imperative in tissue-engineered design as the creation of a successful replacement relies on a thorough understanding of the native anatomy and microanatomical structure. Several studies explore techniques to describe ligament footprints around the body, with limited studies describing in-depth footprint dimensions of the ATFL, CFL and PTFL. Techniques currently used to measure ligament footprints are complex and require resources which may not be readily available, therefore a new methodology may prove beneficial. Objectives. This study explores the application of a novel technique to assess the footprint of ankle ligaments through a straightforward inking method. This method aims to enhance surgical technique and contribute to the development of a tissue-engineered analogue based on real anatomical morphometric data. Methods. Cadaveric dissection of the ATFL, CFL and PTFL was performed on 12 unpaired fresh frozen ankles adhering to regulations of the Human Tissue (Scotland) Act. The ankle complex with attaching ligaments was immersed in methylene blue. Dissection of the proximal and distal entheses of each ligament was carried out to reveal the unstained ligament footprint. Images of each ligament footprint were taken, and the area, length and width of each footprint were assessed digitally. Results. The collective area of the proximal entheses of the ATFL, CFL and PTFL measures 142.11 ± 12.41mm2. The mean areas of the superior (SB) and inferior band (IB) of the distal enthesis of the ATFL measured 41.72 ± 5.01mm2 and 26.66 ± 3.12mm2 respectively. The footprint of the distal enthesis of the CFL measured 146.07 ± 14.05mm2, while the footprint of the distal PTFL measured 126.26 ± 8.88mm2. The proximal footprint of the ATFL, CFL and PTFL measured 11.06 ± 0.69mm, 7.87 ± 0.43mm and 10.52 ± 0.63mm in length and 8.66 ± 0.50mm, 9.10 ± 0.92mm and 14.41 ± 1.30mm in width on average. The distal footprint of the ATFL (SB), ATFL (IB), CFL and PTFL measured 10.92 ± 0.81 mm, 8.46 ± 0.46mm, 13.98 ± 0.93mm and 11.25 ± 0.95mm in length and 7.76 ± 0.59mm, 7.51 ± 0.64mm, 18.98 ± 1.15mm and 24.80 ± 1.25mm in width on average. Conclusions. This methodology provides an effective
Range of Motion (ROM) assessments are routinely used during joint replacement to evaluate joint stability before, during and after surgery to ensure the effective restoration of patient biomechanics. This study aimed to quantify axial torque in the femur during ROM assessment in total hip arthroplasty to define performance criteria against which hip instruments can be verified. Longer term, this information may provide the ability to quantitatively assess joint stability, extending to quantitation of bone preparation and quality. Joint loads measured with strain-gaged instruments in five cadaveric femurs prepared using posterior
Aim of this study was the development of a dynamic FE-framework to identify worst-case size combinations and kinematics in a virtual wear simulator setup covering five daily activities and high, dynamic loads. Two cruciate sacrificing knee designs (D1 & D2) were tested physically on a wear-testing machine prior the model development using a high demanding, daily activity protocol (HDA) [1]. A simplified FE-setup was generated, reduced to the 3D geometries of the assembly whereas the representation of the mechanical wear simulator conditions and the load transmission was achieved by joint elements. Inertial and other time-related effects of the physical situation were compensated by a system of spring- and damper elements. Using a time-series signal optimization
Precision health aims to develop personalised and proactive strategies for predicting, preventing, and treating complex diseases such as osteoarthritis (OA). Due to OA heterogeneity, which makes developing effective treatments challenging, identifying patients at risk for accelerated disease progression is essential for efficient clinical trial design and new treatment target discovery and development. To create a reliable and interpretable precision health tool that predicts rapid knee OA progression over a 2-year period from baseline patient characteristics using an advanced automated machine learning (autoML) framework, “Autoprognosis 2.0”. All available 2-year follow-up periods of 600 patients from the FNIH OA Biomarker Consortium were analysed using “Autoprognosis 2.0” in two separate
Bone regeneration is a complex but very well organized process in which the immune system has a decisive role. The adaptive immune system and its experience level (percentage of effector and memory T cells) has been proven to influence the healing cascade especially in the early healing phases. This opens the possibility of an early intervention to enhance bone healing during the primary clinical treatment. Patients stratified for possible delayed bone healing could benefit from immunomodulatory treatment
Abstract. Introduction. Precision health aims to develop personalised and proactive strategies for predicting, preventing, and treating complex diseases such as osteoarthritis (OA), a degenerative joint disease affecting over 300 million people worldwide. Due to OA heterogeneity, which makes developing effective treatments challenging, identifying patients at risk for accelerated disease progression is essential for efficient clinical trial design and new treatment target discovery and development. Objectives. This study aims to create a trustworthy and interpretable precision health tool that predicts rapid knee OA progression based on baseline patient characteristics using an advanced automated machine learning (autoML) framework, “Autoprognosis 2.0”. Methods. All available 2-year follow-up periods of 600 patients from the FNIH OA Biomarker Consortium were analysed using “Autoprognosis 2.0” in two separate
Introduction and Objective. Posterior and transforaminal lumbar interbody fusion (PLIF, TLIF) represent the most popular techniques in performing an interbody fusion amongst spine surgeons. Pseudarthrosis, cage migration, subsidence or infection can occur, with subsequent failed surgery, persistent pain and patient’ bad quality of life. The goal of revision fusion surgery is to correct any previous technical errors avoiding surgical complications. The most safe and effective way is to choose a naive
Gait analysis is an indispensable tool for scientific assessment and treatment of individuals whose ability to walk is impaired. The high cost of installation and operation are a major limitation for wide-spread use in clinical routine. Advances in Artificial Intelligence (AI) could significantly reduce the required instrumentation. A mobile phone could be all equipment necessary for 3D gait analysis. MediaPipe Pose provided by Google Research is such a Machine Learning
Keywords. Complete Abductor Detachament, Direct Lateral
Primary bone tumors are rare, complex and highly heterogeneous. Its diagnostic and treatment are a challenge for the multidisciplinary team. Developments on tumor biomarkers, immunohistochemistry, histology, molecular, bioinformatics, and genetics are fundamental for an early diagnosis and identification of prognostic factors. The personalized medicine allows an effective patient tailored treatment. The bone biopsy is essential for diagnosis. Treatment may include systemic therapy and local therapy. Frequently, a limb salvage surgery includes wide resection and reconstruction with endoprosthesis, biological or composites. The risk for local recurrence and distant metastases depends on the primary tumor and treatment response. Cancer patients are living longer and bone metastases are increasing. Bone is the third most frequently location for distant lesions. Bone metastases are associated to pain, pathological fractures, functional impairment, and neurological deficits. It impacts survival and patient quality of life. The treatment of metastatic disease is a challenge due to its complexity and heterogeneity, vascularization, reduced size and limited access. It requires a multidisciplinary treatment and depending on different factors it is palliative or curative-like treatment. For multiple bone metastases it is important to relief pain and increases function in order to provide the best quality of life and expect to prolong survival. Advances in nanotechnology, bioinformatics, and genomics, will increase biomarkers for early detection, prognosis, and targeted treatment effectiveness. We are taking the leap forward in precision medicine and personalized care.
Introduction and Objective. Interest for direct anterior approach (DAA) in hip hemiarthroplasty (HHA) has greatly increased in recent years, however which is the best surgical approach in hip replacement treating femoral neck fractures (FNFs) is already unclear. The aim of this study is to perform a radiographic and perioperative complications analysis by comparing the direct anterior approach (DAA) with the direct lateral
Osteoclasts (OCs) are multinucleated cells that play a pivotal role in skeletal development and bone remodeling. Abnormal activation of OCs contributes to the development of bone-related diseases, such as osteoporosis, bone metastasis and osteoarthritis. Restoring the normal function of OCs is crucial for bone homeostasis. Recently, RNA therapeutics emerged as a new field of research for osteoarticular diseases. The aim of this study is to use non-coding RNAs (ncRNAs) to molecularly engineer OCs and modulate their function. Specifically, we investigated the role of the microRNAs (namely miR-16) and long ncRNAs (namely DLEU1) in OCs differentiation and fusion. DLEU1/DLEU2 region, located at chromosome 13q14, also encodes miR-15 and miR-16. Our results show that levels of these ncRNA transcripts are differently expressed at distinct stages of the OCs differentiation. Specifically, silencing of DLEU1 by small interfering RNAs (siDLEU1) and overexpression of miR-16 by synthetic miRNA mimics (miR-16-mimics) led to a significant reduction in the number of OCs formed per field (OC/field), both at day 5 and 9 of the differentiation stage. Importantly, time-lapse analysis, used to track OCs behavior, revealed a significant decrease in fusion events after transfection with siDLEU1 or miR-16-mimics and an alteration in the fusion mode and partners. Next, we investigated the migration profile of these OCs, and the results show that only miR-16-mimics-OCs, but not siDLEU-OCs, have a lower percentage of immobile cells and an increase in cells with mobile regime, compared with controls. No differences in cell shape were found. Moreover, mass-spectrometry quantitative proteomic analysis revealed independent effects of siDLEU1 and miR-16-mimics at the protein levels. Importantly, DLEU1 and miR-16 act by distinct processes and pathways. Collectively, our findings support the ncRNAs DLEU1 and miR-16 as therapeutic targets to modulate early stages of OCs differentiation and, consequently, to impair OC fusion, advancing ncRNA-therapeutics for bone-related diseases.
The future of work brings several challenges and opportunities for occupational health and safety on three major drivers: the rapid progress of technological innovation; demographic changes, in particular ageing of the workforce and migration; and changes in the labour market, especially owing to new ways of per-forming jobs. Innovation technologies are leading to an overall transformation of industrial processes that offer huge developmental perspectives in the world of work and opportunities for society. In the field of prevention of musculoskeletal disorders, relevant progresses have been made in the clinical setting and in the context of care, also in relation to the ageing society. In the near future, the adaptation of workstations and the implementation of sensors and enabling technologies (collaborative robots and exoskeletons) will offer, together with the innovations in the clinic and orthopaedic surgery, a significant contribution to the reduction of risks from biomechanical overload, as well as support interventions to increase work ability and reduce the impact of disability. However, the potential risk scenarios for health and safety in the workplace, along with the progress in occupational health research, lead to the need for creating an inte-grated system of skills and