Osteoarthritis (OA) is a prevalent joint disorder characterized by cartilage degeneration, inflammation, and pain. Current treatments provide only symptomatic relief, necessitating novel molecular targets. The caspase family, known for its roles in apoptosis and inflammation regulation, may additionally influence crucial processes for cartilage homeostasis such as differentiation and proliferation. However, the specific roles of individual caspases in OA pathogenesis remain unclear. This study aims to investigate the involvement of the caspase family in OA and as potential targets for therapy, with a focus on caspase-1 and -8. Chondrocytes from both healthy and OA donors were cultured in 2D and 3D culture models and stimulated with TNF-α or IL-1β. The expression and activation of caspase-1 and -8 was assessed using RT-PCR, ELISA. Transcriptome analysis of OA and healthy cartilage samples, along with Mendelian randomization (MR) analysis were conducted to explore the involvement of caspase family in OA and to assess its potential as therapeutic targets.Introduction
Method
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”. 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 (Introduction
Method
Previous studies have shown the potential for virtual reality (VR) immersion as a promising technique for pain and anxiety management. The aim of our study was to evaluate the feasibility of VR in the management of pain and anxiety during post-op external fixator care procedures. This study involved patients aged 5-21 years following limb lengthening/reconstruction surgery with an external fixator. Aqua VR application from the KindVR® was utilized for this study. Subjects were seen during the first four postoperative visits and assigned to a ‘VR-first’ or ‘no-VR-first’ group. Visits alternated between VR immersion and no VR immersion during care procedures. The study endpoints (pain and anxiety levels) were assessed before, during, and after procedures using the Wong-Baker Faces (FACES) and Children's Fear Scale, respectively. Proxy scores for pain and anxiety were also obtained from parents or legal guardians and providers.Introduction
Method
This study aimed to evaluate the effectiveness of a novel intraoperative navigation platform for total knee arthroplasty (TKA) in restoring native knee joint kinematics and strains in the medial collateral ligament (MCL) and lateral collateral ligament (LCL) during squatting motions. Six cadaver lower limbs underwent computed tomography scans to design patient-specific guides. Using these scans, bony landmarks and virtual single-line collateral ligaments were identified to provide intraoperative real-time feedback, aided in bone resection, implant alignment, tibiofemoral kinematics, and collateral ligament elongations, using the navigation platform. The specimens were subjected to squatting (35°-100°) motions on a physiological Introduction
Method
The main postoperative complications in fixation of ulna shaft fractures are non-union and implant irritation using currently recommended 3.5-mm locking compression plates. An alternative approach using a combination of two smaller plates in orthogonal configuration has been proposed. The aim of this study was to compare the biomechanical properties of a single 3.5-mm locking compression plate versus double plating using one 2.5-mm and one 2.0-mm mandible plate in a human ulna shaft fracture model. Eight pairs human ulnar specimens with a standardized 10-mm fracture gap were pairwise assigned for instrumentation with either a single 3.5-mm plate placed posteriorly, or for double plating using a 2.5-mm and a 2.0-mm mandible plate placed posteriorly under the flexor muscles and laterally under the extensor muscles. All constructs were initially non-destructively biomechanically tested in axial compression, torsion, and bending, which was followed by cyclic torsional loading to failure. Interfragmentary movements were monitored by means of optical motion tracking.Introduction
Method
Osteoarthritis (OA) causes pain, stiffness, and loss of function due to degenerative changes in joint cartilage and bone. In some forms of OA, exercise can alleviate symptoms by improving joint mobility and stability. However, excessive training after joint injury may have negative consequences for OA development. Sensory nerve fibers in joints release neuropeptides like alpha-calcitonin gene-related peptide (alpha-CGRP), potentially affecting OA progression. This study investigates the role of alpha-CGRP in OA pathogenesis under different exercise regimen in mice. OA was induced in C57Bl/6J WT mice and alpha-CGRP KO mice via surgical destabilization of the medial meniscus (DMM) at 12 weeks of age (N=6). Treadmill exercise began 2 weeks post-surgery and was performed for 30 minutes, 5 days a week, for 2 or 6 weeks at intense (16 m/min, 15° incline) or moderate (10 m/min, 5° incline) levels. Histomorphometric assessment of cartilage degradation (OARSI scoring), serum cytokine analysis, immunohistochemistry, and nanoCT analysis were conducted.Introduction
Method
The current methods for measuring femoral torsion have limitations, including variability and inaccuracies. Existing 3D methods are not reliable for abnormal femoral anteversion measurement. A new 3D method is needed for accurate measurement and planning of proximal femoral osteotomies. Currently available software for viewing and modelling CT data lacks measurement capabilities. The MSK Hip planner aims to address these limitations by combining measurement, planning, and analysis functionalities into one tool. We aim to answer 5 key questions: Is there a difference between 2D measurement methods? Is there a difference between 3D measurement methods? Is there a difference between 2D and 3D measurement methods? Are any of the measurement methods affected by the presence of osteoarthritis or a CAM deformity? After segmentation was carried out on 42 femoral CT scans using Osirix, 3D bone models were landmarked in the MSK lab hip planning software. Murphy's, Reikeras’, McBryde, and the novel MSK lab method were used to measure femoral anteversion.Introduction
Method
As per national guidelines for Ankle fractures in the United Kingdom, fractures considered stable can be treated with analgesia, splinting and allowed to weight bear as tolerated. The guidelines also suggest further follow-up not mandatory. This study was aimed at evaluating the current clinical practice of managing stable ankle fractures at a university hospital against national guidelines. The study was undertaken using retrospectively collected data, the inclusion criteria being all adults with stable ankle fracture pattern treated non-operatively between December 2022 and April 2023. Collected data included age of patient, date of injury, type of immobilization, number of clinical visits and any complications.Introduction
Method
Supraspinatus and infraspinatus tears (Massive Rotator Cuff Tear- MRCT) cause compensatory activation of the teres minor (TM) and subscapularis (SubS) to maintain humeral head alignment. This study measures force changes in TM and SubS using a dynamic shoulder testing setup. We hypothesize that combining superior capsule reconstruction (SCR) and lower trapezius tendon (LTT) transfer will correct rotator cuff forces. Eight fresh-frozen human shoulder specimens from donors aged 55-75 (mean = 63.75 years), balanced for gender, averaging 219.5 lbs, were used. Rotator cuff and deltoid tendons were connected to force sensors through a pulley system, with the deltoid linked to a servohydraulic motor for dynamic force measurement. The system allowed unrestricted humeral abduction from 0 to 90 degrees.Introduction
Methods
Intervertebral disc degeneration has been associated with low back pain (LBP) which is a major cause of long-term disability worldwide. Observed mechanical and biological modifications have been related to decreased water content. Clinical traction protocols as part of LBP management have shown positive outcomes. However, the underlying mechanical and biological processes are still unknown. The study purpose was to evaluate the impact of unloading through traction on the mechanobiology of healthy bovine tail discs in culture. We loaded bovine tail discs (n=3/group) 2h/day at 0.2Hz for 3 days, either in dynamic compression (-0.01MPa to -0.2MPa) or in dynamic traction (-0.01MPa to 0.024MPa). In between the dynamic loading sessions, we subjected the discs to static compression loading (-0.048MPa). We assessed biomechanical and biological parameters.Introduction
Method
When designing a new osteosynthesis device, the biomechanical competence must be evaluated with respect to the acting loads. In a previous study, the loads on the proximal phalanx during rehabilitation exercises were calculated. This study aimed to assess the safety of a novel customizable osteosynthesis device compared to those loads to determine when failure would occur. Forty proximal phalanges were dissected from skeletally mature female sheep and divided into four testing groups. A custom 3D printed cutting and drilling guide was used to create a reduced osteotomy and pilot holes to insert four 1.5 mm cortical screws. A novel light-curable polymer composite was used to fixate the bones with an in situ fixation patch. The constructs were tested in cyclic four-point bending in a bioreactor with ringer solution at 37°C with a valley load of 2 N. Four groups (N = 10) had increasing peak loads based on varying safety factors relative to the physiological loading (G1:100x, G2:150x, G3:175x, G4:250x). Each specimen was tested for 12,600 cycles (6 weeks of rehabilitation) or until failure occurred. After the test the thickness of the patch was measured with digital calipers and data analysis was performed in Python and R.Introduction
Method
The molecular mechanisms underlying non-union bone fractures largely remain elusive. Recently, spatial transcriptomics approaches for musculoskeletal tissue samples have been developed requiring direct placement of histology sections on barcoded slides. However, Formalin-Fixed-Paraffin-Embedded (FFPE) bone sections have been associated with limited RNA quality and read depth compared to soft tissue. Here, we test spatial transcriptomics workflows based on transcriptomic probe transfer to characterize molecular features discriminating non-union and union bone fractures in mice. Histological sections (n=8) used for spatial transcriptomics (Visium CytAssist FFPE; 10x Genomics, n=4 on glass slides, n=4 on hydrogel-coated slides) were obtained from a fracture healing study in female 20-week-old C57BL/6J mice receiving either a femur osteotomy (0.7mm) or a segmental defect (2.4mm) (license 22/2022, Grisons CH). Sequence alignment and manual segmentation of different tissues (bone, defect region/callus, bone marrow, muscle) were performed using SpaceRanger and LoupeBrowser (10x Genomics). Differential gene expression was performed using DESeq2 (Seurat) followed by Gene-Set-Enrichment-Analysis (GSEA) of Gene Ontology (ClusterProfiler). Group comparison of quality measures was done using a Welch's t-test. Results are given as mean±standard deviation.Background
Method
The heterogeneity of outcomes used in the field of lower limb lengthening surgery (LLLS) affects our ability to synthesize evidence. This hampers robust systematic reviews and treatment recommendations for clinical practice. Ultimately this reduces the impact of research for both patients and healthcare professionals. This scoping review aimed to describe the outcomes and outcome measurement instruments (OMIs) used within the field of LLLS. A systematic literature search of WOS, Scopus, Embase, MEDLINE, and the Cochrane Library identified all studies reporting outcomes in children and adults after LLLS. All outcomes and OMIs were extracted verbatim. An iterative process was used to group outcome terms under standardized outcome headings categorized using the COMET Taxonomy of Outcomes.Introduction
Method
Low back pain (LBP) is a worldwide leading cause of disability. This preclinical study evaluated the safety of a combined advanced therapy medicinal product developed during the European iPSpine project (#825925) consisting of mesendoderm progenitor cells (MEPC), derived from human induced pluripotent stem cells, in combination with a synthetic poly(N-isopropylacrylamide) hydrogel (NPgel) in an ovine intervertebral disc degeneration (IDD) model. IDD was induced through nucleotomy in 4 adult sheep, 5 lumbar discs each (n=20). After 5 weeks, 3 alternating discs were treated with NPgel (n=6) or NPgel+MEPC (n=6). Before sacrifice, animals were subjected to: MRI of lumbar spines (disc height and Pfirmann grading); blood sampling (hematological, biochemical, metabolic and lymphocyte/monocytes immunological). After 3 months the sheep were sacrificed. The spines were processed for: macroscopic morphology (Thompson grading), microscopic morphology (Histological grading), and glycosaminoglycan content (GAG, DMMB Assay). Furthermore, at sacrifice biodistribution of human MEPC was assessed by Alu-sequences quantification (qPCR) from three tissue samples of heart, liver, spleen, brain, lungs, and kidneys, and PBMCs collected to assess activation of systemic immune cells. To each evaluation, appropriate statistical analysis was applied.Introduction
Method
Homogenous and consistent preparations of mesenchymal stem cells (MSCs) can be acquired by selecting them for integrin α10β1 (integrin a10-MSCs). Safety and efficacy of intra-articular injection of allogeneic integrin a10-MSCs were shown in two post-traumatic osteoarthritis horse studies. The current study investigated immunomodulatory capacities of human integrin a10-MSCs in vitro and their cell fait after intra-articular injection in rabbits. The concentration of produced immunomodulatory factors was measured after licensing integrin a10-MSCs with pro-inflammatory cytokines. Suppression of T-cell proliferation was determined in co-cultures with carboxyfluorescein N-succinimidyl ester (CFSE) labelled human peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3/CD28 and measuring the CFSE intensity of CD4+ cells. Macrophage polarization was assessed in co-cultures with differentiated THP-1 cells stimulated with lipopolysaccharide and analysing the M2 macrophage cell surface markers CD163 and CD206. In vivo homing and regeneration were investigated by injecting superparamagnetic iron oxide nanoparticles conjugated with Rhodamine B-labeled human integrin a10-MSCs in rabbits with experimental osteochondral defects. MSC distribution in the joint was followed by MRI and fluorescence microscopy.Introduction
Method
Patients with external fixators are at risk of pin site infection. A more objective assessment of possible pin site infection is warranted, particularly for future home-based monitoring of pin sites. The aim was to determine if thermography can detect signs of inflammation around pin sites by 1) Establishing a maximum temperature cut-off value 2) Investigating the correlation between local temperature and visual signs of inflammation 3) Adjust for anatomical location and ambient room temperature. This was a cross-sectional international multi-center study following STROBE guidelines. All patients with external ring-fixators scheduled for a visit in the out-patient clinic were eligible. Visual signs of inflammation were categorized using the Modified Gordon classification System (MGS, simplified sMGS). Thermographic imaging was done with an infrared camera (FLIR T540) and the maximum temperature within the ROI (MaxTp) was the primary outcome measure. Sample size and reliability were estimated. Cohen-Kappa, ROC-curve/AUC and Poisson regression were used for statistical analysis.Introduction
Method
Postvoid residualurine (PVR) can be an unknown chronic disorder, but it can also occur after surgery. A pilot-study initiated in Elective Surgery Center, Silkeborg led to collaboration with a urologist to develop a flowchart regarding treatment of PVR. Depending on the severity, men with significant PVR volumes were either recommend follow up by general practitioner or referred to an urologist for further diagnose and/or treatment. Aim: to determine the prevalence of pre- and postoperative PVR in men >65 years undergoing orthopedic surgeries and associated risk factors. A single-center, prospective cohort study. Male patients were consecutively included during one year from April 2022. Data was extracted from the electronic patient files: age, lower urinary tract symptoms (LUTS), co-morbidity (e.g. diabetes), type of surgery and anesthesia, opioid use, pre- and postoperative PVR.Introduction
Method
Approximately 20-25% of patients having joint replacement in the UK have moderate-severe frailty. Frailty is associated with poorer outcomes after joint replacement. Targeting frailty pre-operatively with exercise and protein supplementation could improve post-operative outcomes. Prior to conducting a randomised controlled trial (RCT), a feasibility study was necessary to inform trial design and delivery. We conducted a randomised feasibility study with embedded qualitative work. Patients aged ≥65 years, frail and undergoing THR or TKR were recruited from three UK hospitals. Participants were randomly allocated on a 1:1 ratio to the intervention or usual care group. The intervention group had a 1:1 appointment with a physiotherapist and were provided with a home-based, tailored daily exercise programme and a daily protein supplement for 12 weeks before their operation, supported by six telephone calls from a physiotherapist. Questionnaires were administered at baseline and 12 weeks after randomisation. Interviews were conducted with 19 patients. Feasibility outcomes were eligibility and recruitment rates, intervention adherence, and acceptability of the trial and the intervention.Introduction
Method
This study aims to investigate the relationship between ulnar fixation and postoperative satisfaction among patients with distal radius fractures accompanied by ulna styloid fractures, with a particular focus on how sociodemographic factors influence outcomes. A retrospective cohort study was conducted involving 120 patients aged 26-53 who underwent surgical treatment for distal radius fractures with concomitant ulna styloid fractures between January 2018 and December 2022. Patients were divided into two groups based on whether ulnar fixation was performed. Sociodemographic data, including age, gender, socioeconomic status, education level, and occupation, were collected. All patients underwent similar physical therapy protocols in the postoperative period, and no complications were observed in any patient. Postoperative satisfaction was assessed using the Patient-Rated Wrist Evaluation (PRWE) and the Disabilities of the Arm, Shoulder, and Hand (DASH) scores at 6 and 12 months post-surgery. Statistical analysis was conducted to evaluate the influence of ulnar fixation and sociodemographic factors on patient satisfaction.Introduction
Method
Symptomatic hip dysplasia is often treated with periacetabular osteotomy (PAO). Studies investigating the effect of PAO have primarily focused on radiographic measurements, pain-related outcomes, and hip survival whereas evidence related to sport participation is limited. All patients in our institutional database were deemed eligible for this cohort study if they underwent PAO and had answered at least one question related to sport participation. Patients were asked if they were playing sport preoperatively, 6 months after PAO as well as 2, 5, 10, 15 and 20 years after. In addition, patients were asked if they were able to play their preferred sport, what type and at what level they were playing sport, and if surgery had improved their sport performance.Introduction
Methods
