Total joint arthroplasty (TJA) is one of the commonest and most successful orthopaedic procedures used for the management of end-stage arthritis. With the recent introduction of robotic-assisted joint replacement, Computed tomography (CT) has become part of required pre-operative planning. The aim of this study is to quantify and characterise incidental CT findings, their clinical significance, and their effect on the planned joint arthroplasty. All consecutive patients undergoing an elective TJA (total joint arthroplasty; hip or knee) were retrospectively identified, over a 4-year period (December 2019 and November 2023). Data documented and analysed included patient demographics, type of joint arthroplasty, CT findings, their clinical significance, as well as potential delays to the planned arthroplasty because of these findings and subsequent further investigation. A total of 987 patients (female: 514 patients (52.1%)) undergoing TJA were identified (THA: 444 patients (45.0%); TKA: 400 patients (40.5%); UKA: 143 patients (14.5%)). Incidental findings within imaged areas were identified in 227 patients (23.0%). Of these findings, 74 (7.5%) were significant, requiring further investigation or management, 40 (4.1%) of which represented potential malignancy and 4 (0.4%) resulting in a new cancer diagnosis. A single patient was found to have an aneurysm requiring urgent vascular intervention. Surgery was delayed for further investigation in 4 patients (0.4%). Significant findings were more frequent in THA patients (THA: 43 (9.7%) TKA/UKA: 31 (5.7%) Within our cohort, 74 (7.5%) patients had significant incidental findings that required further investigations or management, with 4 (0.4%) having a previously undiagnosed malignancy. We strongly advocate that all robotic arthroplasty planning CTs are reviewed and reported by a specialist, to avoid missing undiagnosed malignancies and other significant diagnoses.
Biomechanics is an essential form of measurement in the understanding of the development and progression of osteoarthritis (OA). However, the number of participants in biomechanical studies are often small and there is limited ways to share or combine data from across institutions or studies. This is essential for applying modern machine learning methods, where large, complex datasets can be used to identify patterns in the data. Using these data-driven approaches, it could be possible to better predict the optimal interventions for patients at an early stage, potentially avoiding pain and inappropriate surgery or rehabilitation. In this project we developed a prototype database platform for combining and sharing biomechanics datasets. The database includes methods for importing and standardising data and associated variables, to create a seamless, searchable combined dataset of both healthy and knee OA biomechanics. Data was curated through calls to members of the OATech Network+ (Abstract
Objectives
Methods
Knee varus malalignment increases medial knee compartment loading and is associated with knee osteoarthritis (OA) progression and severity1. Altered biomechanical loading and dysregulation of joint tissue biology drive OA progression, but mechanistic links between these factors are lacking. Subchondral bone structural changes are biomechanically driven, involve bone resorption, immune cell influx, angiogenesis, and sensory nerve invasion, and contribute to joint destruction and pain2. We have investigated mechanisms underlying this involving RANKL and alkaline phosphatase (ALP), which reflect bone resorption and mineralisation respectively3 and the axonal guidance factor Sema3A. Sema3A is osteotropic, expressed by mechanically sensitive osteocytes, and an inhibitor of sensory nerve, blood vessel and immune cell invasion4. Sema3A is also differentially expressed in human OA bone5.HYPOTHESIS: Medial knee compartment overloading in varus knee malalignment patients causes dysregulation of bone derived Sema3A signalling directly linking joint biomechanics to pathology and pain. Synovial fluid obtained from 30 subjects with medial knee OA (KL grade II-IV) undergoing high tibial osteotomy surgery (HTO) was analysed by mesoscale discovery and ELISA analysis for inflammatory, neural and bone turnover markers. 11 of these patients had been previously analysed in a published patient-specific musculoskeletal model6 of gait estimating joint contact location, pressure, forces, and medial-lateral condyle load distribution in a published data set included in analyses. Data analysis was performed using Pearson's correlation matrices and principal component analyses. Principal Components (PCs) with eigenvalues greater than 1 were analysed.Abstract
OBJECTIVE
METHODS
Changes in subchondral bone are one of few disease characteristics to correlate with pain in OA1. Profound neuroplasticity and nociceptor sprouting is displayed within osteoarthritic (OA) subchondral bone and is associated with pain and pathology2. The cause of these neural changes remains unestablished. Correct innervation patterns are indispensable for bone growth, homeostasis, and repair. Axon guidance signalling factor, Sema3A is essential for the correct innervation patterning of bony tissues3, expressed in osteocytes4 and known to be downregulated in bone OA mechanical loading5. Bioinformatic analysis has also shown Sema3a as a differentially expressed pathway by bone in human OA patients6.HYPOTHESIS: Pathological mechanical load and inflammation of bone causes dysregulation of Sema3A signalling leading to perturbed sensory nerve plasticity and pain. Human KOLF2-C1 iPSC derived nociceptors were generated by TALEN-mediated insertion of transcription factors NGN2+Brn3A and modified chambers differentiation protocol to produce nociceptor-like cells. Nociceptor phenotype was confirmed by immunocytochemistry. Human Y201-MSC cells were embedded in 3D type-I collagen gels (0.05 × 106 cell/gel), in 48-well plates and silicone plates, were differentiated to osteocytes for 7 days before stimulation with IL-6 (5ng/ml) and soluble IL-6 receptor (sIL-6r (40ng/ml), IL6/sIL6r and mechanical load mimetic Yoda1 (5μM) or unstimulated (n=5/group) (48-well plates) or were mechanically loaded in silicone plates (5000μstrain, 10Hz, 3000 cycles) or not loaded (n=5/group). Conditioned media transfer was performed from osteocyte to nociceptor cultures assessed by continuous 24-hour phase contrast confocal microscopy. 24-hours after stimulation RNA was quantified by RT-qPCR (IL6) or RNAseq whole transcriptome analysis/DEseq2 analysis (Load). Protein release was quantified by ELISA. Normally distributed data with homogenous variances was analysed by two-tailed t test.Abstract
OBJECTIVE
METHODS
Total joint arthroplasty (TJA) is one of the commonest and most successful orthopaedic procedures, used for the management of end-stage arthritis. With the recent introduction of robotic assisted joint replacement, Computed Tomography (CT) has become part of required pre-operative planning. The aim of this study is to quantify and characterise incidental CT findings, their clinical significance, and their effect on planned joint arthroplasty. All consecutive patients undergoing an elective TJR (hip or knee arthroplasty) were retrospectively identified, over a 3-year period (December 2019 and December 2022). Data documented and analysed included patient demographics, type of joint arthroplasty, CT findings, their clinical significance, as well as potential delays to the planned arthroplasty because of these findings and subsequent further investigation.Abstract
Introduction
Methodology
Stimulation of the mechanosensitive ion channel, Piezo1 promotes bone anabolism and SNPs in the Piezo1 locus are associated with changes in fracture risk. Osteocytes function as critical regulators of bone homeostasis by sensing mechanical signals. The current study used a human, cell-based physiological, 3D in vitro model of bone to determine whether loading of osteocytes in vitro results in upregulation of the Piezo1 pathway. Human Y201 MSCs, embedded in type I collagen gels and differentiated to osteocytes for 7-days, were subjected to pathophysiological load (5000 µstrain, 10Hz, 5 mins; n=6) with unloaded cells as controls (n=4). RNA was extracted 1-hr post load and assessed by RNAseq analysis. To mimic mechanical load and activate Piezo1, cells were differentiated to osteocytes for 13 days and treated ± Yoda1 (5µM, 2- and 24-hs, n=4); vehicle treated cells served as controls (n=4). RNA was subjected to RT-qPCR and data normalised to the housekeeping gene, YWHAZ. Media was analysed for IL6 release by ELISA. Mechanical load upregulated Piezo1 gene expression (16.5-fold, p<0.001) and expression of the transcription factor NFATc1, and matricellular protein CYR61, known regulators of Piezo1 mechanotransduction (3-fold; p= 5.0E-5 and 6.8-fold; p= 6.0E-5, respectively). After 2-hrs, Yoda1 increased the expression of the early mechanical response gene, cFOS (11-fold; p=0.021), mean Piezo1 expression (2.3-fold) and IL-6 expression (103-fold, p<0.001). Yoda1 increased the release of IL6 protein after 24 hours (7.5-fold, p=0.001). This study confirms Piezo1 as an important mechanosensor in osteocytes. Piezo1 activation mediated an increase in IL6, a cytokine that drives inflammation and bone resorption providing a direct link between mechanical activation of Piezo1, bone remodeling and inflammation, which may contribute to mechanically induced joint degeneration in diseases such as osteoarthritis. Mechanistically, we hypothesize this may occur through promoting Ca2+ influx and activation of the NFATc1 signaling pathway.
Osteoarthritis (OA) is a common cause of chronic pain. Subchondral bone is highly innervated, and bone structural changes directly correlate with pain in OA. Mechanisms underlying skeletal–neural interactions are under-investigated. Bone derived axon guidance molecules are known to regulate bone remodelling. Such signals in the nervous system regulate neural plasticity, branching and neural inflammation. Perturbation of these signals during OA disease progression may disrupt sensory afferents activity, affecting tissue integrity, nociception, and proprioception. Osteocyte mechanical loading and IL-6 stimulation alters axon guidance signalling influencing innervation, proprioception, and nociception. Human Y201 MSC cells, embedded in 3D type I collagen gels (0.05 × 106 cell/gel) in 48 well plastic or silicone (load) plates, were differentiated to osteocytes for 7 days before stimulation with IL-6 (5ng/ml) with soluble IL-6 receptor (sIL-6r (40ng/ml) or unstimulated (n=5/group), or mechanically loaded (5000 μstrain, 10Hz, 3000 cycles) or not loaded (n=5/group). RNA extracted 1hr and 24hrs post load was quantified by RNAseq whole transcriptome analysis (NovaSeq S1 flow cell 2 × 100bp PE reads and differentially expressed neurotransmitters identified (>2-fold change in DEseq2 analysis on normalised count data with FDR p<0.05). After 24 hours, extracted IL-6 stimulated RNA was quantified by RT-qPCR for neurotrophic factors using 2–∆∆Ct method (efficiency=94-106%) normalised to reference gene GAPDH (stability = 1.12 REfinder). Normally distributed data with homogenous variances was analysed by two-tailed t test. All detected axonal guidance genes were regulated by mechanical load. Axonal guidance genes were both down-regulated (Netrin1 0.16-fold, p=0.001; Sema3A 0.4-fold, p<0.001; SEMA3C (0.4-fold, p<0.001), and up-regulated (SLIT2 2.3-fold, p<0.001; CXCL12 5-fold, p<0.001; SEMA3B 13-fold, p<0.001; SEMA4F 2-fold, p<0.001) by mechanical load. IL6 and IL6sR stimulation upregulated SEMA3A (7-fold, p=0.01), its receptor Plexin1 (3-fold, p=0.03). Neutrophins analysed in IL6 stimulated RNA did not show regulation. Here we show osteocytes regulate multiple factors which may influence innervation, nociception, and proprioception upon inflammatory or mechanical insult. Future studies will establish how these factors may combine and affect nerve activity during OA disease progression.
Mechanical loading of joints with osteoarthritis (OA) results in pain-related functional impairment, altered joint mechanics and physiological nociceptor interactions leading to an experience of pain. However, the current tools to measure this are largely patient reported subjective impressions of a nociceptive impact. A direct measure of nociception may offer a more objective indicator. Specifically, movement-induced physiological responses to nociception may offer a useful way to monitor knee OA. In this study, we gathered preliminary data on healthy volunteers to analyse whether integrated biomechanical and physiological sensor datasets could display linked and quantifiable information to a nociceptive stimulus. Following ethical approval, 15 healthy volunteers completed 5 movement and stationary activities in 2 conditions; a control setting and then repeated with an applied quantified thermal pain stimulus to their right knee. An inertial measurement unit (IMU) and an electromyography (EMG) lower body marker set were tested and integrated with ground reaction force (GRF) data collection. Galvanic skin response electrodes for skin temperature and conductivity and photoplethysmography (PPG) sensors were manually timestamped to the integrated system. Pilot data showed EMG, GRF and IMU fluctuations within 0.5 seconds of each other in response to a thermal trigger. Preliminary analysis on the 15 participants tested has shown skin conductance, PPG, EMG, GRFs, joint angles and kinematics with varying increases and fluctuations during the thermal condition in comparison to the control condition. Preliminary results suggest physiological and biomechanical data outputs can be linked and identified in response to a defined nociceptive stimulus. Study data is currently founded on healthy volunteers as a proof-of-concept. Further exploratory statistical and sensor readout pattern analysis, alongside early and late-stage OA patient data collection, can provide the information for potential development of wearable nociceptive sensors to measure disease progression and treatment effectiveness.
Involving research users in setting priorities for research is essential to ensure research outcomes are patient-centred and to maximise research value and impact. The Musculoskeletal (MSK) Disorders Research Advisory Group Versus Arthritis led a research priority setting exercise across MSK disorders. The Child Health and Nutrition Research Initiative (CHRNI) method of setting research priorities with a range of stakeholders were utilised. The MSKD RAG identified, through consensus, four research Domains: Mechanisms of Disease; Diagnosis and Impact; Living Well with MSK disorders and Successful Translation. Following ethical approval, the research priority exercise involved four stages and two surveys, to: 1) gather research uncertainties; 2) consolidate these; 3) score uncertainties using agreed criteria of importance and impact on a score of 1–10; and 4) analyse scoring, for prioritisation.Background
Methods
Geniculate nerve blocks (GNB) and ablation (GNA) are increasing in popularity as strategies for the management of knee pain in patients unsuitable for surgical intervention. Typically these simple blocks have been performed by specialists in pain medicine. We present the results of a GNB clinic run by a surgical care practitioner (SCP). An SCP clinic was created where ultrasound-guided GNBs comprising local anaesthetic and steroid were administered. Patients considered unsuitable for surgery were referred with knee pain by orthopaedic knee surgeons and specialist physiotherapists. A VAS pain score and an Oxford Knee Score (OKS) were completed prior to and immediately following blockade. Serial VAS diaries were completed. Further OKS were requested at 6 weeks and 6 months. Patients could request GNA at any point during follow-up and their follow-up ceased at this stage.Abstract
INTRODUCTION
METHODOLOGY
The burden of prosthetic joint infection (PJI) in total knee arthroplasty (TKA) has been rising in line with the number of primary operations performed. Current estimates suggest an infection rate of 1–2.4%. Two-stage revision has traditionally been considered the gold standard of treatment; however, some studies suggest comparable results can be achieved with single-stage procedures. The potential advantages include less time in hospital, a single anaesthetic, reduced costs, and greater patient satisfaction. We reviewed data for 72 patients (47 males, 25 females), with a mean age of 71 years (range, 49 to 94), who underwent single-stage revision TKA for confirmed PJI between 2006 and 2016. A standardized debridement protocol was performed with immediate single-stage exchange. All cases were discussed preoperatively at multidisciplinary team (MDT) meetings, which included input from a senior musculoskeletal microbiologist. Patients were not excluded for previous revisions, culture-negative PJI, or the presence of a sinus.Introduction
Methods
Knee tactile afferents act as synovial joint limit detectors, eliciting signalling upon excessive fibrous tissue strain but play little role in joint function as disruption of their activity does not induce impairments in movement or sensation. In contrast, knee nociceptive afferents gain activity upon inflammation producing painful sensation in pathology such as osteoarthritis. We hypothesize that similar in origin, fast-conducting tactile afferents become sensitized by inflammatory mediators and gain activity causing proprioceptive sensation impairment in patients with knee pathology, driving gait abnormalities and osteoarthritis progression. To investigate the activity of these neurons, we will produce a co-culture model using our existing 3D bone mimetic and iPSC derived tactile sensory neurons by utilizing the NGN2-BRN3A plasmid produced by Nickolls et al producing a model of these tactile neurons at their position within the joint at the fibrous/bony interface. Human Y201 MSC cells embedded in type I collagen gels (0.05 × 106 cell/gel) were differentiated to osteocytes andmechanically loaded in silicone plates (5000 µstrain, 10Hz, 3000 cycles) (n=5). RNA quantified by RNAseq analysis (NovaSeq S1) and neuronal communication pathways identified using DEseq2 analysis.Abstract
INTRODUCTION
METHODS
Current tools to measure pain are broadly subjective impressions of the impact of the nociceptive impulse felt by the patient. A direct measure of nociception may offer a more objective indicator. Specifically, movement-induced physiological responses to nociception may offer a useful way to monitor knee OA. In this proof-of-concept study, we evaluated whether integrated biomechanical and physiological sensor datasets could display linked and quantifiable information to a nociceptive stimulus. Following ethical approval, we applied a quantified thermal pain stimulus to a volunteer during stationary standing in a gait lab setting. An inertial measurement unit (IMU) and an electromyography (EMG) lower body marker set were tested and integrated with ground reaction force (GRF) data collection. Galvanic skin response electrodes and skin thermal sensors were manually timestamp linked to the integrated system.Abstract
Objectives
Method
Determining proper joint tension in reverse total shoulder arthroplasty (rTSA) can be a challenging task for shoulder surgeons. Often, this is a subjective metric learned by feel during fellowship training with no real quantitative measures of what proper tension encompasses. Tension too high can potentially lead to scapular stress fractures and limitation of range of motion (ROM), whereas tension too low may lead to instability. New technologies that detect joint load intraoperatively create the opportunity to observe rTSA joint reaction forces in a clinical setting for the first time. The purpose of this study was to observe the differences in rTSA loads in cases that utilized two different humeral liner sizes. Ten different surgeons performed a total of 37 rTSA cases with the same implant system. During the procedure, each surgeon reconstructed the rTSA implants to his or her own preferred tension. A wireless load sensing humeral liner trial (VERASENSE for Equinoxe, OrthoSensor, Dania Beach, FL) was used in lieu of a traditional plastic humeral liner trial to provide real-time load data to the operating surgeon during the procedure. Two humeral liner trial sizes were offered in 38mm and 42mm curvatures and were selected each case based on surgeon preference. To ensure consistent measurements between surgeons, a standardized ROM assessment consisting of four dynamic maneuvers (maximum internal to external rotation at 0°, 45°, and 90° of abduction, and a maximum flexion/extension maneuver) and three static maneuvers (arm overhead, across the body, and behind the back) was completed in each case. Deidentified load data in lbf was collected and sorted based on which size liner was selected. Differences in means for minimum and maximum load values for the four dynamic maneuvers and differences in means for the three static maneuvers were calculated using 2-tailed unpaired t-tests.INTRODUCTION
METHODS
Periprosthetic joint infection (PJI) is a devastating complication following total knee arthroplasty (TKA). Two-stage revision has traditionally been considered the gold standard of treatment for established infection, but increasing evidence is emerging in support of one-stage exchange for selected patients. The objective of this study was to determine the outcomes of single-stage revision TKA for PJI, with mid-term follow-up. A total of 84 patients, with a mean age of 68 years (36 to 92), underwent single-stage revision TKA for confirmed PJI at a single institution between 2006 and 2016. In all, 37 patients (44%) were treated for an infected primary TKA, while the majority presented with infected revisions: 31 had undergone one previous revision (36.9%) and 16 had multiple prior revisions (19.1%). Contraindications to single-stage exchange included systemic sepsis, extensive bone or soft-tissue loss, extensor mechanism failure, or if primary wound closure was unlikely to be achievable. Patients were not excluded for culture-negative PJI or the presence of a sinus.Aims
Methods
The mechanisms underlying abnormal joint mechanics are poorly understood despite it being a major risk factor for developing osteoarthritis. This study investigated the response of a 3D in vitro bone cell model to mechanical load. Human MSC cells (Y201) embedded in 3D type I collagen gels were differentiated in osteogenic media for 7-days in deformable, silicone plates. Gels were loaded once (5000 µstrain, 10Hz, 3000 cycles), RNA extracted 1-hr post load and assessed by RT-qPCR and RNAseq analysis (n=5/treatment). Cell shape and phenotype were assessed by immunocytochemistry and phalloidin staining. Data was analysed by Minitab.Abstract
Objectives
Methods
3D preoperative planning software for anatomic and reverse total shoulder arthroplasty (ATSA and RTSA) provides additional insight for surgeons regarding implant selection and placement. Interestingly, the advent of such software has brought previously unconsidered questions to light on the optimal way to plan a case. In this study, a survey of shoulder specialists from the American Shoulder and Elbow Society (ASES) was conducted to examine thought patterns in current glenoid implant selection and placement. 172 ASES members completed an 18-question survey on their thought process for how they select and place a glenoid implant for both ATSA and RTSA procedures. Data was collected using a custom online Survey Monkey survey. Surgeon answers were split into three cohorts based on their responses to usage of 3D preoperative planning software: high users, seldom users, and non-users. Data was analyzed for each cohort to examine differences in thought patterns, implant selection, and implant placement.INTRODUCTION
METHODS
The advent of CT based 3D preoperative planning software for reverse total shoulder arthroplasty (RTSA) provides surgeons with more data than ever before to prepare for a case. Interestingly, as the usage of such software has increased, further questions have appeared over the optimal way to plan and place a glenoid implant for RTSA. In this study, a survey of shoulder specialists from the American Shoulder and Elbow Society (ASES) was conducted to examine thought patterns in current RTSA implant selection and placement. 172 ASES members completed an 18-question survey on their thought process for how they select and place a RTSA glenoid implant. Data was collected using a custom online Survey Monkey survey. Surgeon answers were split into two cohorts based on number of arthroplasties performed per year: between 0–75 was considered low volume (LV), and between 75–200+ was considered high volume (HV). Data was analyzed for each cohort to examine differences in thought patterns, implant selection, and implant placement.INTRODUCTION
METHODS
3D preoperative planning software for anatomic total shoulder arthroplasty (ATSA) provides surgeons with increased ability to visualize complex joint relationships and deformities. Interestingly, the advent of such software has seemed to create less of a consensus on the optimal way to plan an ATSA rather than more. In this study, a survey of shoulder specialists from the American Shoulder and Elbow Society (ASES) was conducted to examine thought patterns in current ATSA implant selection and placement. 172 ASES members completed an 18-question survey on their thought process for how they select and place an ATSA glenoid implant. Data was collected using a custom online Survey Monkey survey. Surgeon answers were split into two cohorts based on number of arthroplasties performed per year: between 0–75 was considered low volume (LV), and between 75–200+ was considered high volume (HV). Data was analyzed for each cohort to examine differences in thought patterns, implant selection, and implant placement.INTRODUCTION
METHODS
