Abstract. Introduction.
MicroRNA (miR) delivery to regulate chronic inflammation hold extraordinary promise, with new therapeutic possibilities emanating from their ability to fine-tune multiple target gene regulation pathways which is an important factor in controlling aberrant inflammatory reactions in complex multifactorial disease. However, several hurdles have prevented advancements in miR-based therapies. These include off-target effects of miRs, limited trafficking, and inefficient delivery. We propose a magnetically guided nanocarrier to transport therapeutically relevant miRs to assist self- resolving inflammation processes at injury sites and reduce the impact of chronic inflammation- related diseases such as tendinopathies. The high prevalence, significant socio-economic burden and increasing recognition of dysregulated immune mediated pathways in tendon disease provide a compelling rationale for exploring inflammation-targeting strategies as novel treatments in this condition. By combining cationic polymers, miR species (e.g., miR 29a, miR155 antagonist), and magnetic nanoparticles in the form of magnetoplexes with highly efficient magnetofection procedures, we developed inexpensive, easy-to-fabricate, and biocompatible systems with competent miR-binding and fast cellular uptake into different types of human cells, namely macrophages and tendon-derived cells. The system was shown to be cell-compatible and to successfully modulate the expression and production of inflammatory markers in tendon cells, with evidence of functional pro-healing changes in immune cell phenotypes. Hence, magnetoplexes represent a simple, safe, and non-viral nanoplatform that enables contactless miR delivery and high-
DVC is a novel full-field and contactless measurement technique for calculating displacements and strains inside bones (Grassi and Isaksson 2015) through the comparison of 3D reconstructions (CT, micro-CT, MRI, etc.) from unloaded and loaded samples. Recent in zero-strain tests to estimate the measurement
Magnetic resonance imaging (MRI) is a useful diagnostic tool in evaluating meniscus pathology in the knee. Data from available literature suggests sensitivity and specificity rates around 90% when compared to the gold standard findings at knee arthroscopy. We sought to evaluate the sensitivity, specificity and
Our aim was to determine the
Background. Trust in the validity of a measurement tool is critical to its function in both clinical and educational settings. Acetabular cup malposition within total hip arthroplasty (THA) can lead to increased dislocation rates, impingement and increased wear as a result of edge loading. We have developed a THA simulator incorporating a foam/Sawbone pelvis model with a modified Microsoft HoloLens® augmented reality (AR) headset. We aimed to measure the trueness,
Mobility plays an important role, in particular for patients with osteoporosis and after trauma surgery, both as an outcome and as treatment. Mobility is closely linked to the patient”s quality of life and exercise is a powerful additional treatment option. In order to be able to generate an evidence base to evaluate various surgical and non-surgical treatment options, objective measurements of patient mobility and exercise over a certain time period are needed. Wearables are a promising candidate, with obvious advantages compared to questionnaires and/or PROs. However, when extracting parameters with wearables, one often faces the problem of algorithms not performing well enough for special cases like slow gait speeds or impaired gait, as they typically appear in this patient group. We plan to further extend the applicability of the actibelt system (3D accelerometer, 100Hz), in particular to improve the measurement
Chronic low back pain (cLBP) is a complex, multifaceted disorder where biological, psychological, and social factors affect its onset and trajectory. Consequently, cLBP encompasses many different disease variants, with multiple patient-specific mechanisms. The goal of NIH Back Pain Consortium (BACPAC) Research Program is to develop understanding of cLBP mechanisms and to develop algorithms that optimally match specific treatments to individual patients. To accomplish this, one research activity of BACPAC is to develop theoretical models for chronic low back pain based on the current state of knowledge in the scientific community, and to interrogate the relationships implied by the theoretical models using data generated by or available to BACPAC. The models consider biopsychosocial perspectives, and encompass both peripheral (i.e. low back) and central (i.e. spinal and supra-spinal) factors as well as proposed mechanisms of action of cLBP treatments. However, absent explanations, models/algorithms may fall short of regulatory requirements and clinician expectations, and ultimately may not be embraced by physicians and patients. To address this, BACPAC is developing a clinical utility roadmap (CUR) to clarify how models will be used in practice for selecting optimal treatments, monitoring response to treatment, and reducing health care utilization. This presentation will review the goals of BACPAC and how theoretical models and CUR are being used to support computational knowledge networks to integrate data from deeply phenotyped cLBP patients.
Our aim was to determine whether tantalum markers improved the accuracy and/or
Introduction.
Weight-bearing is a known stimulus for bone remodelling and a reduction in weight-bearing is associated with reduced bone mineral density (BMD) in affected limbs post lower limb fracture. This study investigated short and long-term
The heat produced by drills, saws and PMMA cement in the handling of bone can cause thermal necrosis. Thermal necrosis could be a factor in the formation of a fibrous tissue membrane and impaired bony ingrowth into porous prostheses. This has been proposed to lead to non-union of osteotomies and fractures, the failure of the bone-cement interface and the failure of resurfacing arthroplasty. We compared three proprietary blades (the De Soutter, the Stryker Dual Cut and the Stryker Precision) in an in-vitro setting with porcine tibiae, using thermocouples embedded in the bone below the cutting surface to measure the increases in bone temperature. There was a significant (p=0.001) difference in the change in temperature (δT) between the blade types. The mean increase in temperature was highest for the De Soutter, 2.84°C (SD: 1.83°C, range 0.48°C to 9.30°C); mean δT was 1.81°C (SD: 1.00°C, range 0.18°C to 4.85°C) for the
Chronic inflammatory events have been associated to almost every chronic disease, including cardiovascular-, neurodegenerative- and autoimmune- diseases, cancer, and host-implant rejection. Given the toll of chronic inflammation in healthcare and socioeconomical costs developing strategies to resolve and control chronic states of inflammation remain a priority for the significant benefit of patients. Macrophages (Mφ) hold a central role both in the initiation and resolution of inflammatory events, assuming different functional profiles. The outstanding features of Mφ counting with the easy access to tissues, and the extended networking make Mφ excellent candidates for
Introduction. With advances in artificial intelligence, the use of computer-aided detection and diagnosis in clinical imaging is gaining traction. Typically, very large datasets are required to train machine-learning models, potentially limiting use of this technology when only small datasets are available. This study investigated whether pretraining of fracture detection models on large, existing datasets could improve the performance of the model when locating and classifying wrist fractures in a small X-ray image dataset. This concept is termed “transfer learning”. Method. Firstly, three detection models, namely, the faster region-based convolutional neural network (faster R-CNN), you only look once version eight (YOLOv8), and RetinaNet, were pretrained using the large, freely available dataset, common objects in context (COCO) (330000 images). Secondly, these models were pretrained using an open-source wrist X-ray dataset called “Graz Paediatric Wrist Digital X-rays” (GRAZPEDWRI-DX) on a (1) fracture detection dataset (20327 images) and (2) fracture location and classification dataset (14390 images). An orthopaedic surgeon classified the small available dataset of 776 distal radius X-rays (Arbeidsgmeischaft für Osteosynthesefragen Foundation / Orthopaedic Trauma Association; AO/OTA), on which the models were tested. Result. Detection models without pre-training on the large datasets were the least precise when tested on the small distal radius dataset. The model with the best accuracy to detect and classify wrist fractures was the YOLOv8 model pretrained on the GRAZPEDWRI-DX fracture detection dataset (mean average
To detect early signs of infection infrared thermography has been suggested to provide quantitative information. Our vision is to invent a pin site infection thermographic surveillance tool for patients at home. A preliminary step to this goal is the aim of this study, to automate the process of locating the pin and detecting the pin sites in thermal images efficiently, exactly, and reliably for extracting pin site temperatures. A total of 1708 pin sites was investigated with Thermography and augmented by 9 different methods in to totally 10.409 images. The dataset was divided into a training set (n=8325), a validation set (n=1040), and a test set (n=1044) of images. The Pin Detection Model (PDM) was developed as follows: A You Only Look Once (YOLOv5) based object detection model with a Complete Detection Intersection over Union (CDIoU), it was pre-trained and finetuned by the through transfer learning. The basic performance of the YOLOv5 with CDIoU model was compared with other conventional models (FCOS and YOLOv4) for deep and transition learning to improve performance and
Non-linear methods in statistical shape analysis have become increasingly important in orthopedic research as they allow for more accurate and robust analysis of complex shape data such as articulated joints, bony defects and cartilage loss. These methods involve the use of non-linear transformations to describe shapes, rather than the traditional linear approaches, and have been shown to improve the
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
The computational modelling and 3D technology are finding more and more applications in the medical field. Orthopedic surgery is one of the specialties that can benefit the most from this solution. Three case reports drawn from the experience of the authors’ Orthopedic Clinic are illustraded to highlight the benefits of applying this technology. Drawing on the extensive experience gained within the authors’ Operating Unit, three cases regarding different body segments have been selected to prove the importance of 3D technology in preoperative planning and during the surgery. A sternal transplant by allograft from a cryopreserved cadaver, the realization of a custom made implant of the glenoid component in a two-stage revision of a reverse shoulder arthroplasty, and a case of revision on a hip prosthesis with acetabular bone loss (Paprosky 3B) treated with custom system. In all cases the surgery was planned using 3D processing software and models of the affected bone segments, printed by 3D printer, and based on CT scans of the patients. The surgical implant was managed with dedicated instruments. The use of 3D technology can improve the results of orthopedic surgery in many ways: by optimizing the outcomes of the operation as it allows a preliminary study of the bone loss and an evalutation of feasibility of the surgery, it improves the