bluuebunny/crossref_metadata_2025_split huggingface dataset:
CLINICAL AND RADIOLOGICAL OUTCOMES OF CUSTOM 3D-PRINTED GLENOID COMPONENTS IN PRIMARY AND REVISION REVERSE POLARITY TOTAL SHOULDER ARTHROPLASTY WITH SEVERE GLENOID BONE LOSS: A MINIMUM TWO-YEAR FOLLOW-UP
Authors: Rashid M. , Cunningham L. , Walton M. , Monga P. , Bale S. , Trail I. 
Published: July 2023

The purpose of this study is to report the clinical and radiological outcomes of patients undergoing primary or revision reverse total shoulder arthroplasty using custom 3D printed components to manage severe glenoid bone loss with a minimum of 2-year follow-up.After ethical approval (reference: 17/YH/0318), patients were identified and invited to participate in this observational study. Inclusion criteria included: 1) severe glenoid bone loss necessitating the need for custom implants; 2) patients with definitive glenoid and humeral components implanted more than 2 years prior; 3) ability to comply with patient reported outcome questionnaires. After seeking consent, included patients underwent clinical assessment utilising the Oxford Shoulder Score (OSS), Constant-Murley score, American Shoulder and Elbow Society Score (ASES), and quick Disabilities of the Arm, Shoulder, and Hand Score (quickDASH). Radiographic assessment included AP and axial projections. Patients were invited to attend a CT scan to confirm osseointegration. Statistical analysis utilised included descriptive statistics (mean and standard deviation) and paired t test for parametric data.3 patients had revision surgery prior to the 2-year follow-up. Of these, 2/3 retained their custom glenoid components. 4 patients declined to participate. 5 patients were deceased at the time of commencement of the study. 21 patients were included in this analysis. The mean follow-up was 36.1 months from surgery (range 22–60.2 months). OSS improved from a mean 16 (SD 9.1) to 36 (SD 11.5) (p < 0.001). Constant-Murley score improved from mean 9 (SD 9.2) to 50 (SD 16.4) (p < 0.001). QuickDASH improved from mean 67 (SD 24) to 26 (SD 27.2) (p = 0.004). ASES improved from mean 28 (SD 24.8) to 70 (SD 23.9) (p = 0.007). Radiographic evaluation demonstrated good osseointegration in all 21 included patients.The utility of custom 3D-printed components for managing severe glenoid bone loss in primary and revision reverse total shoulder arthroplasty yields significant clinical improvements in this complex patient cohort.
ASSESSING THE CHANGE IN FRICTION AND DEFORMATION OVER TIME IN HEALTHY VERSUS HAEMARTHRITIC ARTICULAR CARTILAGE
Authors: Sharrock M. , Fermor H. , Redmond A. , Brockett C. 
Published: July 2023

This study aims to assess the changes in mechanical behaviour over time in ‘haemarthritic’ articular cartilage compared to ‘healthy’ articular cartilage.Pin-on-plate and indentation tests were used to determine the coefficient of friction (COF) and deformation of ‘healthy’ and ‘haemarthritic articular cartilage. Osteochondral pins (8 mm) were extracted from porcine tali and immersed in exposure fluid for two hours prior to test. Pins were articulated against a larger bovine femoral plate for 3600 seconds under a load of 50 N. Osteochondral pins (8 mm) were loaded during indentation testing for 3600 seconds under a load of 0.25 N. To mimic the effect of a joint bleed in vitro; serum, whole blood and 50% v/v were used as exposure and lubricant fluids. COF and deformation were expressed as mean (n=3) and statistically analysed using a one-way ANOVA and post-hoc Tukey test (p>0.05).The serum condition yielded a COF of 0.0428 ± 0.02 with 0.08mm ± 0.04 deformation. The 50% v/v condition produced a higher COF of 0.0485 ± 0.02 and 0.21mm ± 0.04 deformation. The lowest COF and deformation were produced by the whole blood condition (0.0292 ± 0.02 and 0.06mm ± 0.006 respectively). Statistical analysis indicated no significant difference across the friction test conditions but a significant difference across all indentation test conditions (ANOVA, p>0.05). Combination of creep deformation and wear was observed on the articular surface up to 24 hours post-test in 50% v/v and whole blood conditions.The average haemophilia patient can experience multiple joint bleeds per year of which this study demonstrates the effect of just one joint bleed. This study has provided evidence of potential reversible and irreversible mechanical changes to articular cartilage surface during a joint bleed.
INVESTIGATING THE FORMATION OF 3D BONE CELL SPHEROIDS FOR SCAFFOLD-FREE BONE TISSUE ENGINEERING
Authors: Prabhakaran V. , Hawkswell R. , Paxton J. 
Published: July 2023

3D spheroid culture is a bridge between standard 2D cell culture and in vivo research which mimics the physiological microenvironment in scaffold-free conditions. Here, this 3D technique is being investigated as a potential method for engineering bone tissue in vitro. However, spheroid culture can exhibit limitations, such as necrotic core formation due to the restricted access of oxygen and nutrients. It is therefore important to determine if spheroids without a sizeable necrotic core can be produced. This study aims to understand necrotic core formation and cell viability in 3D bone cell spheroids using different seeding densities and media formulations.Differentiated rat osteoblasts (dRObs) were seeded in three different seeding densities (1×104, 5×104, 1×10 cells) in 96 well U-bottom cell-repellent plates and in three different media i.e., Growth medium (GM), Mineralisation medium 1 (MM1) and MM2. Spheroids were analysed from day 1 to 28 (N=3, n=2). Cell count and viability was assessed by trypan blue method. One way ANOVA and post-hoc Tukey test was performed to compare cell viability among different media and seeding densities. Histological spheroid sections were stained with hematoxylin and eosin (H&E) to identify any visible necrotic core.Cell number increased from day 1 to 28 in all three seeding densities with a notable decrease in cell viability. 1×104 cells proliferated faster than 5×104 and 1×105 cells and had proportionately similar cell death. The necrotic core area was relatively equivalent between all cell seeding densities. The larger the spheroid size, the larger is the size of the necrotic core.This study has demonstrated that 3D spheroids can be formed from dRobs at a variety of seeding densities with no marked difference in necrotic core formation. Future studies will focus on utilising the bone cell spheroids for engineering scalable scaffold-free bone tissue constructs.
IN VITRO METHODOLOGY FOR SYSTEMATIC CT INVESTIGATION OF THE PERICLAVICULAR SPACE
Authors: Gehweiler D. , Pastor T. , Gueorguiev B. , Jaeger M. , Lambert S. 
Published: July 2023

The periclavicular space is a conduit for the brachial plexus and subclavian-axillary vascular system. Changes in its shape/form generated by alteration in the anatomy of its bounding structures, e.g. clavicle malunion, cause distortion of the containing structures, particularly during arm motion, leading to syndromes of thoracic outlet stenosis etc., or alterations of scapular posture with potential reduction in shoulder function.Aim of this study was developing an in vitro methodology for systematic and repeatable measurements of the clinically poorly characterized periclavicular space during arm motion using CT-imaging and computer-aided 3D-methodologies.A radiolucent frame, mountable to the CT-table, was constructed to fix an upper torso in an upright position with the shoulder joint lying in the isocentre. The centrally osteotomized humerus is fixed to a semi-circular bracket mounted centrally at the end of the frame. All arm movements (ante-/retroversion, abduction/elevation, in-/external rotation) can be set and scanned in a defined and reproducible manner. Clavicle fractures healed in malposition can be simulated by osteotomy and fixation using a titanium/carbon external fixator.During image processing the first rib served as fixed reference in space. Clavicle, scapula and humerus were registered, segmented, and triangulated. The different positions were displayed as superimposed surface meshes and measurements performed automatically. Initial results of an intact shoulder girdle demonstrated that different arm positions including ante-/retroversion and abduction/elevation resulted solely in a transverse movement of the clavicle along/parallel to the first rib maintaining the periclavicular space.A radiolucent frame enabling systematic and reproducible CT scanning of upper torsos in various arm movements was developed and utilized to characterize the effect on the 3D volume of the periclavicular space. Initial results demonstrated exclusively transverse movement of the clavicle along/parallel to the first rib maintaining the periclavicular space during arm positions within a physiological range of motion.
VALIDATION OF A VIRTUAL REALITY SIMULATOR FOR INTRAMEDULLARY FEMORAL NAIL APPLICATION DURING AN ORTHOPAEDIC SURGICAL COURSE
Authors: Sharma M. , Khanal P. , Patel N. , Patel A. 
Published: July 2023

To investigate the utility of virtual reality (VR) simulators in improving surgical proficiency in Orthopaedic trainees for complex procedures and techniques.Fifteen specialty surgeons attending a London Orthopaedic training course were randomised to either the VR (n = 7) or control group (n = 8). All participants were provided a study pack comprising an application manual and instructional video for the Trochanteric Femoral Nail Advanced (TFNA) procedure. The VR group underwent additional training for TFNA using the DePuy Synthes (Johnson and Johnson) VR simulator. All surgeons were then observed applying the TFNA in a Sawbones model and assessed by a blinded senior consultant using three metrics: time to completion, 22-item procedure checklist and 5-point global assessment scale.Participant demographics for the VR and control groups were similar in context of age (mean [SD]: VR group, 31.0 [2.38] years; control group, 30.6 [2.39] years), gender (VR group, 5 [71%] men; control group, 8 [100%] men) and prior experience with TFNA (had applied TFNA as primary surgeon: VR group, 6 [86%]; control group, 7 [88%]). Although statistical significance was not reached, the VR group, on average, outperformed the control group on all three metrics. They completed the TFNA procedure faster (mean [SD]: 18.2 [2.16] minutes versus 19.78 [1.32] minutes; p<0.189), performed a greater percentage of steps correctly (79% versus 66%; p<0.189) and scored a higher percentage on the global assessment scale (75% versus 65%; p<0.232).VR simulators offer a safe and accessible means for Orthopaedic trainees to prepare for and supplement their theatre-based experience. It is vital, therefore, to review and validate novel simulation-based systems and in turn facilitate their improvement. We intend to increase our sample size and expand this preliminary study through a second upcoming surgical course for Orthopaedic trainees in London.
STIMULAN® IN ORTHOPAEDIC SURGERY: TECHNIQUE AND INDICATIONS FOR USE
Authors: Troiano E. , Giacomo P. , Di Meglio M. , Nuvoli N. , Mondanelli N. , Giannotti S. , Orlandi N.C. 
Published: July 2023

Infections represent a devastating complication in orthopedic and traumatological surgery, with high rates of morbidity and mortality. An early intervention is essential, and it includes a radical surgical approach supported by targeted intravenous antimicrobial therapy. The availability of parenteral antibiotics at the site of infection is usually poor, so it is crucial to maximize local antibiotic concentration using local carriers. Our work aims to describe the uses of one of these systems, Stimulan®, for the management and prevention of infections at our Institution.Analysing the reported uses of Stimulan®, we identified two major groups: bone substitute and carrier material for local antibiotic therapy. The first group includes its application as a filler of dead spaces within bone or soft tissues resulting from traumatic events or previous surgery. The second group comprehends the use of Stimulan® for the treatment of osteomyelitis, post-traumatic septic events, periprosthetic joint infections, arthroplasty revision surgery, prevention in open fractures, surgery of the diabetic foot, oncological surgery and for all those patients susceptible to a high risk of infection.We used Stimulan® in several complex clinical situations: in PJIs, in DAPRI procedure and both during the first and the second stage of a 2-stage revision surgery; furthermore, we started to exploit this antibiotic carrier also in prophylaxis of surgical site infections, as it happens in open fractures, and when a surgical site remediation is required, like in osteomyelitis following ORIF. Stimulan® is an extremely versatile and polyhedric material, available in the form of beads or paste, and can be mixed to a very broad range of antibiotics to better adapt to different bacteria and their antibiograms, and to surgeon's needs. These properties make it a very useful adjuvant for the management of complex cases of infection, and for their prevention, as well.
ANATOMICAL ANALYSIS OF DIFFERENT HELICAL PLATE DESIGNS FOR PROXIMAL HUMERAL SHAFT FRACTURE FIXATION
Authors: Pastor T. , Kastner P. , Souleiman F. , Gehweiler D. , Link B-C. , Beeres F. , Babst R. , Gueorguiev B. , Knobe M. 
Published: July 2023

Helical plates are preferably used for proximal humeral shaft fracture fixation and potentially avoid radial nerve irritation as compared to straight plates. Aims:(1) to investigate the safety of applying different long plate designs (straight, 45°-, 90°-helical and ALPS) in MIPO-technique to the humerus. (2) to assess and compare their distances to adjacent anatomical structures at risk.MIPO was performed in 16 human cadaveric humeri using either a straight plate (group1), a 45°-helical (group2), a 90°-helical (group3) or an ALPS (group4). Using CT-angiography, distances between brachial arteries and plates were evaluated. Following, all specimens were dissected, and distances to the axillary, radial and musculocutaneous nerve were evaluated.None of the specimens demonstrated injuries of the anatomical structures at risk after MIPO with all investigated plate designs. Closest overall distance (mm(range)) between each plate and the radial nerve was 1(1-3) in group1, 7(2-11) in group2, 14(7-25) in group3 and 6(3-8) in group4. It was significantly longer in group3 and significantly shorter in group1 as compared to all other groups, p<0.001. Closest overall distance (mm(range)) between each plate and the musculocutaneous nerve was 16(8-28) in group1, 11(7-18) in group2, 3(2-4) in group3 and 6(3-8) in group4. It was significantly longer in group1 and significantly shorter in group3 as compared to all other groups, p<0.001. Closest overall distance (mm(range)) between each plate and the brachial artery was 21(18-23) in group1, 7(6-7) in group2, 4(3-5) in group3 and 7(6-7) in group4. It was significantly longer in group1 and significantly shorter in group3 as compared to all other groups, p<0.021.MIPO with 45°- and 90°-helical plates as well as ALPS is safely feasible and showed a significant greater distance to the radial nerve compared to straight plates. However, distances remain low, and attention must be paid to the musculocutaneous nerve and the brachial artery when MIPO is used with ALPS, 45°- and 90°-helical implants. Anterior parts of the deltoid insertion will be detached using 90°-helical and ALPS implants in MIPO-technique.
PREDICTION OF FRAGILE FRACTURE USING DEEP LEARNING BASED ON ULTRASOUND RADIOFREQUENCY SIGNAL: A PILOT STUDY
Authors: Ding Y. , Luo W. , Chen Z. , Guo P. , Lei B. , Zhang Q. , Chen Z. , Fu Y. , Li C. , Ma T. , Liu J. 
Published: July 2023

Quantitative ultrasound (QUS) is a promising tool to estimate bone structure characteristics and predict fragile fracture. The aim of this pilot cross-sectional study was to evaluate the performance of a multi-channel residual network (MResNet) based on ultrasonic radiofrequency (RF) signal to discriminate fragile fractures retrospectively in postmenopausal women.MethodsRF signal and speed of sound (SOS) were obtained using an axial transmission QUS at one‐third distal radius for 246 postmenopausal women. Based on the involved RF signal, we conducted a MResNet, which combines multi-channel training with original ResNet, to classify the high risk of fragility fractures patients from all subjects. The bone mineral density (BMD) at lumber, hip and femoral neck acquired with DXA was recorded on the same day. The fracture history of all subjects in adulthood were collected. To assess the ability of the different methods in the discrimination of fragile fracture, the odds ratios (OR) calculated using binomial logistic regression analysis and the area under the receiver operator characteristic curves (AUC) were analyzed.ResultsAmong the 246 postmenopausal women, 170 belonged to the non-fracture group, 50 to the vertebral group, and 26 to the non-vertebral fracture group. MResNet was discriminant for all fragile fractures (OR = 2.64; AUC = 0.74), for Vertebral fracture (OR = 3.02; AUC = 0.77), for non-vertebral fracture (OR = 2.01; AUC = 0.69). MResNet showed comparable performance to that of BMD of hip and lumbar with all types of fractures, and significantly better performance than SOS all types of fractures.Conclusionsthe MResNet model based on the ultrasonic RF signal can significantly improve the ability of QUS device to recognize previous fragile fractures. Moreover, the performance of the proposed model modified by age, weight, and height is further optimized. These results open perspectives to evaluate the risk of fragile fracture applying a deep learning model to analyze ultrasonic RF signal.
TAK1 MEDIATES HMGB1-INDUCED MACROPHAGE ACTIVATION IN OSTEOARTHRITIS
Authors: Li C. , Ding Y. , Li S. , Lin S. , Wen Z. , Ouyang Z. 
Published: July 2023

Osteoarthritis, the most common degenerative joint disease, significantly impairs life quality and labor capability of patients. Synovial inflammation, initiated by HMGB1 (High mobility group box 1)-induced activation of macrophage, precedes other pathological changes. As an upstream regulator of NF-κB (nuclear factor-kappa B) and MAPK (mitogen-activated protein kinase) signaling pathway, TAK1 (TGF-β activated kinase 1) participates in macrophage activation, while its function in osteoarthritis remains unveiled. This study aims to investigate the role of TAK1 in the pathogenesis of osteoarthritis via both in vitro and in vivo approaches.We performed immunohistochemical staining for TAK1 in synovial tissue, both in osteoarthritis patients and healthy control. Besides, immunofluorescence staining for F4/80 as macrophage marker and TAK1 were conducted as well. TAK1 expression was examined in RAW264.7 macrophages stimulated by HMGB1 via qPCR (Quantitative polymerase chain reaction) and Western blotting, and the effect of TAK1 inhibitor (5z-7 oxozeaenol) on TNF-α production was evaluated by immunofluorescence staining. Further, we explored the influence of intra-articular shRNA (short hairpin RNA) targeting TAK1 on collagenase-induced osteoarthritis in mice.Immunohistochemical staining confirmed significant elevation of TAK1 in osteoarthritic synovium, and immunofluorescence staining suggested macrophages as predominant residence of TAK1. In HMGB1-stimulated RAW264.7 macrophages, TAK1 expression was up-regulated both in mRNA and protein level. Besides, TAK1 inhibitor significantly impairs the production of TNF-α by macrophages upon HMGB1 stimulation. Moreover, intra-articular injection of lentivirus loaded with shRNA targeting TAK1 (sh-TAK1) reduced peri-articular osteophyte formation in collagenase-induced osteoarthritis in mice.TAK1 exerts a potent role in the pathogenesis of osteoarthritis by mediating the activation of macrophages.
‘STING’ PROMOTES TITANIUM PARTICLE-INDUCED MACROPHAGE INFLAMMATION
Authors: Ouyang Z. , Ding Y. , Lin S. , Wen Z. 
Published: July 2023

Aseptic inflammation is the main factor causing aseptic loosening of artificial joints. Studies have shown that inflammatory cells can activate STING (stimulator of interferon genes, STING) after being stressed. This study aims to explore the specific mechanism of STING in aseptic loosening of artificial joints, and provide new strategies for disease prevention.Titanium particles with a diameter of 1.2-10 μm were prepared to stimulate macrophages (RAW 264.7) to simulate the periprosthetic microenvironment. A lentiviral vector targeting the STING gene was designed and transfected into macrophages to construct a cell line targeting STING knockdown. The expression and secretion levels of TNF-α were detected by qPCR and ELISA, the activation levels of inflammatory pathways (NF-κB, IRF3, etc.) were detected by western blot, and the nucleus translocation of P65 and IRF3 was observed by cellular immunofluorescence.After titanium particles stimulated macrophages, qPCR and ELISA showed that the transcription and secretion levels of TNF-α were significantly increased. Western blot showed that titanium particle stimulation could increase the phosphorylation levels of NF-κB and IRF3 pathways. While knockdown of STING can significantly reduce titanium particle-induced TNF production, attenuate the activation levels of NF-κB and IRF3 pathways as well as the nucleus translocation of P65 and IRF3.Conclusions: STING positively regulates the level of inflammation in macrophages induced by titanium particles, and targeted inhibition of STING can reduce inflammation, which may delay the progression of aseptic loosening of artificial joints.
MELATONIN REVERSES TUMOUR NECROSIS FACTOR-ALPHA–INDUCED METABOLIC DISTURBANCE OF HUMAN NUCLEUS PULPOSUS CELLS VIA MTNR1B/GΑI2/YAP SIGNALLING
Authors: Qiu X. , Ding Y. , Huang D. 
Published: July 2023

Intervertebral disc degeneration (IDD), the main cause of low back pain, is closely related to the inflammatory microenvironment in the nucleus pulposus (NP). Tumor necrosis factor-α (TNF-α) plays an important role in inflammation-related metabolic disturbance of NP cells. Melatonin has been proven to regulate the metabolism of NP cells, but whether it can protect NP cells from TNF-α-induced damage is still unclear. Therefore, this study aims to investigate the role and specific mechanism of melatonin on regulating the metabolism of NP cells in the inflammatory microenvironment.Human primary NP cells were treated with or without vehicle, TNF-α and melatonin. And the metabolic markers were also detected by western blotting and RT-qPCR. The activity of NF-κB signaling and Hippo/YAP signaling were assessed by western blotting and immunofluorescence. Membrane receptors inhibitors, pathway inhibitors, lentiviral infection, plasmids transfection and immunoprecipitation were used to explore the specific mechanism of melatonin. In vivo, the rat IDD model were constructed and melatonin was injected intraperitoneally to evaluate its therapeutical effect on IDD.We demonstrated that melatonin could alleviate the development of IDD in a rat model and reverse TNF-α–impaired metabolism of NP cells in vitro. Further investigation revealed that the protective effects of melatonin on NP cells mainly rely on MTNR1B, which subsequently activates Gαi2 protein. The activation of Gαi2 could upregulate the yes-associated protein (YAP) level, resulting in anabolic enhancement of NP cells. In addition, melatonin-mediated YAP upregulation increased the expression of IκBα and suppressed the TNF-α–induced activation of the NF-κB pathway, thereby inhibiting the catabolism of NP cells.Our results revealed that melatonin can reverse TNF-α–impaired metabolism of NP cells via the MTNR1B/Gαi2/YAP axis and suggested that melatonin can be used as a potential therapeutic drug in the treatment of IDD.