bluuebunny/crossref_metadata_2025 huggingface dataset:
EARLY RECOVERY FOLLOWING TOTAL HIP ARTHROPLASTY IS ASSOCIATED WITH THE ADJACENT MUSCLE QUALITY
Authors: Halvorson R. T. , Khattab K. , Ngwe H. , Ornowski J. , Akkaya Z. , Matthew R. P. , Souza R. , Bird A. , Lotz J. , Vail T. P. , Bailey J. F.
Published: July 2023

Patients demonstrate distinct trajectories of recovery after THA. The purpose of this study was to assess the impact of adjacent muscle quality on postoperative hip kinematics. We hypothesized that patients with better adjacent muscle quality (less fatty infiltration) would have greater early biomechanical improvement.

Adults undergoing primary THA were recruited. Preoperative MRI was obtained and evaluated via Scoring Hip Osteoarthritis with MRI Scores (SHOMRI, Lee, 2015). Muscle quality was assessed by measuring fat fraction [FF] from water-fat sequences. Biomechanics were assessed preoperatively and six weeks postoperatively during a staggered stance sit-to-stand using the Kinematic Deviation Index (KDI, Halvorson, 2022). Spearman's rho was used to assess correlations between muscle quality and function.

Ten adults (5M, 5F) were recruited (average age: 60.1, BMI: 23.79, SHOMRI: 40.6, KDI: 2.96). Nine underwent a direct anterior approach and one a posterior approach. Preoperatively, better biomechanical function was very strongly correlated with lower medius FF (rho=0.89), strongly correlated with lower FF in the minimus (rho=0.75) and tensor fascia lata (TFL) FF (rho=0.70), and weakly correlated with SHOMRI (rho=0.29). At six weeks, greater biomechanical improvement was strongly correlated with lower minimus FF (rho=0.63), moderately correlated with medius FF (rho=0.59), and weakly correlated with TFL FF (rho=0.26) and SHOMRI (rho=0.39). Lastly, medius FF was moderately correlated with SHOMRI (rho=0.42) with negligible correlations between SHOMRI and FF in the minimus and TFL.

These findings suggest adjacent muscle quality may be related to postoperative function following THA, explaining some of the variability and supporting specialized muscle rehabilitation or regeneration therapy to improve outcomes.
DEVELOPMENT AND IMPLEMENTATION OF A “SURGEON OUTLIER” POLICY FOR THE NEW ZEALAND NATIONAL JOINT REGISTRY
Authors: Devane P.
Published: July 2023

At the end of 2018, the NZ Joint Registry introduced a “Surgeon Outlier” policy, whereby each year, if an individual surgeons’ lower 95% confidence interval of their revision rate, measured in revision/100 component years(r/ocys), was above the NZ mean (0.71 r/ocys), that surgeon was required to audit their results with a nominated peer. This study investigates whether outlier surgeons also have high early (1 month and 1 year) revision rates.

In 2018, 236 surgeons performed 9,186 total hip arthroplasties in NZ. At the end of 2018, 11 surgeons received notification they were outliers. Results from all surgeons for years 2016, 2017 and 2018 were combined to form the first (pre-notification) time interval, and results from years 2019, 2020 and 2021 were combined to form the second time interval (post-notification). Outlier surgeons performed 2001 total hip replacements in the first time interval and 1947 hips in the second. Early revision rates (1 month and 1 year) of both outlier and nonoutlier surgeons for both time intervals were analysed.

Non-outlier surgeons had a consistent mean early revision rate of 0.75% at one month and 1.6% at one year for both time intervals. The 11 outlier surgeons had a higher earlier revision rate of 1.35% at one month and 2.45% at one year for the pre-notification time interval. These values reduced for the post-notification time interval to a revision rate of 1.23% for one month and 2.36% for one year.

Poor joint registry results of individual surgeons are often attributed to a poor choice of prosthesis. This study shows early revision rates of outlier surgeons, where prosthesis selection has minimal influence, are also high.

A slight improvement in early revision rates of outlier surgeons since introduction of the policy shows it is working.
EFFECT OF ENHANCE RECOVERY PATHWAY (ERP) RESULTING IN REDUCED LENGTH OF STAY AND OPIOID CONSUMPTION AFTER NON FUSION ANTERIOR SCOLIOSIS CORRECTION (NFASC) SURGERY FOR ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS): A SINGLE-CENTRE EXPERIENCE
Authors: Akbari K. , Kanade U. , Meena S. , Roopan V. , Hegde S.
Published: July 2023

The current study aims to find the role of Enhance Recovery Pathway (ERP) as a multidisciplinary approach aimed to expedite rapid recovery, reduce LOS, and minimize morbidity associated with Non Fusion Anterior Scoliosis Correction (NFASC) surgery.

A retrospective analysis of 35 AIS patients who underwent NFASC with Lenke 1 and Lenke 5 curves with a minimum of 1 year of follow-up was done. Patient demographics, surgical details, postoperative analgesia, mobilization, length of stay (LOS), patient satisfaction survey score with respect to information and care, and 90 days complications were collected.

The cohort included 34 females and 1 male with a mean age of 15.2 years at the time of surgery. There were 16 Lenke 1 and 19 Lenke 5 in the study. Mean preoperative major thoracic and thoracolumbar/lumbar Cobb's angle were 52˚±7.6˚ and 51˚±4.5˚ respectively. Average blood loss and surgical time were 102 ±6.4 ml and 168 ± 10.2 mins respectively. Average time to commencing solid food was 6.5±1.5 hrs. Average time to mobilization following surgery was 15.5± 4.3 hrs. The average duration to the stopping of the epidural was 42.5±3.5 hrs. The average dose of opioid consumption intraoperatively was 600.5±100.5 mcg of fentanyl i.v. and 12.5±4.5 mg morphine i.v. Postoperatively opioids were administered via an epidural catheter at a dose of 2 mg of morphine every 24 hours up to 2 days and an infusion of 2mcg/hr of fentanyl along with 0.12-0.15% ropivacaine. The average duration to transition to oral analgesia was 55.5±8.5 hrs .20 patients had urinary catheter and the average time to removal of the catheter was 17.5±1.4 hrs. 25 patients had a chest tube and the average time to remove of chest tube was 25.5±3.2 hrs. The average length of hospital stay was 3.1±0.5 days. No patient had postoperative ileus or requirement of blood transfusion or any other complications. No correlation was found between LOS and initial cobb angle.

The application of ERP in AIS patients undergoing NFASC results in reduced LOS and indirectly the cost, reduced post-operative opioid use, and overall improve patient satisfaction score.
ACTIVATION OF OSTEOBLASTS BY COBALT-CHROMIUM OCCURS VIA A TLR4-MEDIATED PATHWAY
Authors: Jamieson S. , Mawdesley A. , Hyde P. , Kirby J. , Tyson-Capper A.
Published: July 2023

Total hip replacement (THR) is indicated for patients with osteoarthritis where conservative treatment has failed. Metal alloys used in THR implants such as cobalt-chromium (CoCr) have been known to cause pro-inflammatory reactions in patients, therefore leading to the need for costly revision surgery. This study therefore aimed to investigate the role of TLR4 in the activation of a human osteoblast model in response to CoCr particles in vitro.

Human osteoblasts (MG-63 cell line) were seeded at a density of 100,000 cells and treated with 0.5, 5, 50mm3 CoCr particles per cell for 24-hours. Trypan blue and the XTT Cell Proliferation Kit II were then used in conjunction with the cells to assess CoCr-induced cytotoxicity. Cells were pre-treated with a commercially available TLR4-specific small molecule inhibitor (CLI-095) for 6 hours. Untreated cells were used as a negative control and lipopolysaccharide (LPS) was used as a positive control. Following treatment the cell supernatant was collected and used for enzyme-linked immunosorbant assay (ELISA) to measure the secretion of interleukin-8 (IL-8), CXCL10, and interleukin-6 (IL-6).

Trypan blue and XTT analysis showed that there was no significant changes to cell viability or proliferation at any dose used of CoCr after 24 hours. There was a significant increase in protein secretion of IL-8 (p<0.001), CXCL10 (p<0.001), and IL-6 (p<0.001) in the cells which received the highest dosage of CoCr. This pro-inflammatory secretory response was ameliorated by TLR4 blockade (p<0.001).

CoCr particles are not cytotoxic to osteoblasts but they do induce pro-inflammatory changes as characterised by increased secretion of chemokines IL-8, CXCL10, and IL-6. These responses occur via a TLR4-mediated pathway and upon inhibition they can be effectively ameliorated. This is particularly important as TLR4 could be a potential target for pharmacological intervention used in patients experiencing immunological reactions to metal implant debris.
ASSESSMENT OF TIBIOFEMORAL AND ALLOGRAFT LOADING AFTER OSTEOCHONDRAL ALLOGRAFT TRANSPLANTATION USING SHELL GRAFTS
Authors: Luk J.
Published: July 2023

In this study, we aimed to investigate tibiofemoral and allograft loading parameters after OCA transplantation using tibial plateau shell grafts to characterize the clinically relevant biomechanics that may influence joint kinematics and OCA osseointegration after transplantation. The study was designed to test the hypothesis that there are significant changes in joint loading after tibial plateau OCA transplantation that may require unique post-operative rehabilitation regimens in patients to restore balance in the knee joint.

Fresh-frozen cadaveric knees (n=6) were thawed and mounted onto a 6 DOF KUKA robot. Specimens were size matched to +2 mm for the medial-to-lateral width of the medial tibial hemiplateaus. Three specimens served as allograft recipient knees and three served as donor knees. Recipient knees were first tested in their native state and then tested with size-matched medial tibial hemiplateau shell grafts (n=3) prepared from the donor knees using custom-cut tab-in-slot and subchondral drilling techniques. Tekscan sensors were placed in the joint spaces to evaluate the loading conditions under 90N biaxial loading at full extension of the knee before and after graft placement. The I-Scan system used in conjunction analyzed the total force, pressure distribution, peak pressure, and center of force within the joint space.

Data demonstrated significant difference (p<0.05) in joint space loading after graft implantation compared to controls in both lateral and medial tibial plateaus. The I-Scan pressure mapping system displayed changes in femoral condylar contact points as well.

The results demonstrated that joint space loading was significantly different (p<0.05) between all preoperative and postoperative cadaveric specimens. Despite the best efforts to size match grafts, slight differences in the host's joint geometry resulted in shifts of contact areas between the tibial plateau and femoral condyle therefore causing either an increase or decrease in pressure measured by the sensor. This concludes that accuracy in graft size matching is extremely important to restoring close to normal loading across the joint and this can be further ensured through postoperative care customized to the patient after OCA surgery.
BETTER ANTEROPOSTERIOR TRANSLATION AND AXIAL TIBIOFIBULAR JOINT STABILITY PROVIDED BY NOVEL DYNAMIC SCREW-SUTURE STABILIZATION SYSTEM FOR SYNDESMOTIC REPAIR
Authors: Souleiman F. , Zderic I. , Pastor T. , Gehweiler D. , Gueorguiev B. , Galie J. , Kent T. , Tomlinson M. , Schepers T. , Swords M.
Published: July 2023

The quest for optimal treatment of acute distal tibiofibular syndesmotic disruptions is still in full progress. Using suture-button repair devices is one of the dynamic stabilization options, however, they may not be always appropriate for stabilization of length-unstable syndesmotic injuries. Recently, a novel screw-suture repair system was developed to address such issues. The aim of this study was to investigate the performance of the novel screw-suture repair system in comparison to a suture-button stabilization of unstable syndesmotic injuries.

Eight pairs of human cadaveric lower legs were CT scanned under 700 N single-leg axial loading in five foot positions – neutral, 15° external/internal rotation and 20° dorsi-/plantarflexion – in 3 different states: (1) pre-injured (intact); (2) injured, characterized by complete syndesmosis and deltoid ligaments cuts simulating pronation-eversion injury types III and IV, and supination-eversion injury type IV according to Lauge-Hansen; (3) reconstructed, using a screw-suture (FIBULINK, Group 1) or a suture-button (TightRope, Group 2) implants for syndesmotic stabilization, placed 20 mm proximal to the tibia plafond/joint surface. Following, all specimens were: (1) biomechanically tested over 5000 cycles under combined 1400 N axial and ±15° torsional loading; (2) rescanned. Clear space (diastasis), anterior tibiofibular distance, talar dome angle and fibular shortening were measured radiologically from CT scans. Anteroposterior, axial, mediolateral and torsional movements at the distal tibiofibular joint level were evaluated biomechanically via motion tracking.

In each group clear space increased significantly after injury (p ≤ 0.004) and became significantly smaller in reconstructed compared with both pre-injured and injured states (p ≤ 0.041). In addition, after reconstruction it was significantly smaller in Group 1 compared to Group 2 (p < 0.001). Anteroposterior and axial movements were significantly smaller in Group 1 compared with Group 2 (p < 0.001). No further significant differences were detected between the groups (p ≥ 0.113).

Conclusions

Although both implant systems demonstrate ability for stabilization of unstable syndesmotic injuries, the screw-suture reconstruction provides better anteroposterior translation and axial stability of the tibiofibular joint and maintains it over time under dynamic loading. Therefore, it could be considered as a valid option for treatment of syndesmotic disruptions.
TIBIAL CORTEX TRANSVERSE TRANSPORT ACCELERATES WOUND HEALING VIA ENHANCED ANGIOGENESIS AND IMMUNOMODULATION
Authors: Yang Y. , Li Y. , Pan Q. , Wang H. , Bai S. , Pan X. , Ling K-K. , Li G.
Published: July 2023

Treatment for delayed wound healing resulting from peripheral vascular diseases and diabetic foot ulcers remain a challenge. A novel surgical technique named Tibial Cortex Transverse Transport has been developed for treating peripheral ischaemia, with encouraging clinical effects. However, its underlying mechanisms remain unclear. In present study, we aimed to explore the wound healing effects after undergoing this novel technique via multiple ways.

A novel rat model of Tibial Cortex Transverse Transport was established with a designed external fixator and effects on wound healing were investigated. All rats were randomized into 3 groups, with 12 rats per group: sham group (negative control), fixator group (positive control) and Tibial Cortex Transverse Transport group. Laser speckle perfusion imaging, vessel perfusion, histology and immunohistochemistry were used to evaluate the wound healing processes.

Gross and histological examinations showed that Tibial Cortex Transverse Transport technique accelerated wound closure and enhanced the quality of the newly formed skin tissues. In Tibial Cortex Transverse Transport group, HE staining demonstrated a better epidermis and dermis recovery, while immune-histochemical staining showed that Tibial Cortex Transverse Transport technique promoted local collagen deposition. Tibial Cortex Transverse Transport technique also benefited to angiogenesis and immunomodulation. In Tibial Cortex Transverse Transport group, blood flow in the wound area was higher than that ofother groups according to laser speckle imaging with more blood vessels observed. Enhanced neovascularization was seen in the Tibial Cortex Transverse Transport group with double immune-labelling of CD31 and α-SMA. The M2 macrophages at the wound site in the Tibial Cortex Transverse Transport group was also increased.

Tibial cortex transverse transport technique accelerated wound healing through enhanced angiogenesis and immunomodulation.
POSTERIOR PELVIC TILT AND CUP POSITION CHANGES IN PATIENTS UNDERGOING TOTAL HIP ARTHROPLASTY: RADIOLOGICAL STUDY WITH A MINIMUM FOLLOW-UP OF TEN YEARS
Authors: García-Rey E. , Saldaña L.
Published: July 2023

Pelvic tilt can vary over time due to aging and the possible appearance of sagittal spine disorders. Cup position in total hip arthroplasty (THA) can be influenced due to these changes. We assessed the evolution of pelvic tilt and cup position after THA and the possible appearance of complications for a minimum follow-up of ten years.

343 patients received a THA between 2006 and 2009. All were diagnosed with primary osteoarthritis and their mean age was 63.3 years (range, 56 to 80). 168 were women and 175 men. 250 had no significant lumbar pathology, 76 had significant lumbar pathology and 16 had lumbar fusion. Radiological analysis included sacro-femoral-pubic (SFP), acetabular abduction (AA) and anteversion cup (AV) angles. Measurements were done pre-operatively and at 6 weeks, and at five and ten years post-operatively. Three measurements were recorded and the mean obtained at all intervals. All radiographs were evaluated by the same author, who was not involved in the surgery.

There were nine dislocations: six were solved with closed reduction, and three required cup revision. All the mean angles changed over time; the SFP angle from 59.2º to 60º (p=0.249), the AA angle from 44.5º to 46.8º (p=0.218), and the AV angle from 14.7º to 16.2º (p=0.002). The SFP angle was lower in older patients at all intervals (p<0.001). The SFP angle changed from 63.8 to 60.4º in women and from 59.4º to 59.3º in men, from 58.6º to 59.6º (p=0.012). The SFP angle changed from 62.7º to 60.9º in patients without lumbar pathology, from 58.6º to 57.4º in patients with lumbar pathology, and from 57.0º to 56.4º in patients with a lumbar fusion (p=0.919). The SFP cup angle was higher in patients without lumbar pathology than in the other groups (p<0.001), however, it changed more than in patients with lumbar pathology or fusion at ten years after THA (p=0.04).

Posterior pelvic tilt changed with aging, influencing the cup position in patients after a THA. Changes due to lumbar pathology could influence the appearance of complications long-term.
THE USE OF IMAGING MASS CYTOMETRY TO INVESTIGATE THE POTENTIAL ROLE OF MITOCHONDRIAL DEFICIENCY IN OSTEOPOROSIS
Authors: Hipps D. , Dobson P. , Warren C. , Russell O. , Turnbull D. , Deehan D. , Lawless C.
Published: July 2023

We have developed a novel technique to analyse bone, using imaging mass cytometry (IMC) without the constraints of using immunofluorescent histochemistry. IMC can measure the expression of over 40 proteins simultaneously, without autofluorescence. We analysed mitochondrial respiratory chain (RC) protein deficiencies in human bone which are thought to contribute to osteoporosis with increasing age.

Osteoporosis is characterised by reduced bone mineral density (BMD) and fragility fractures. Humans accumulate mitochondrial mutations and RC deficiency with age and this has been linked to the changing phenotype in advancing age and age-related disease. Mitochondrial mutations are detectable from the age of 30 onwards, coincidently the age BMD begins to decline. Mitochondria contain their own genome which accumulates somatic variants at around 10 times the rate of nuclear DNA. Once these mutations exceed a threshold, RC deficiency and cellular dysfunction occur. The PolgD257A/D257A mouse model expresses a proof-reading deficient version of PolgA, a mtDNA polymerase. These mice accumulate mutations 3-5 times higher than wild-type mice showing enhanced levels of age-related osteoporosis and RC deficiency in osteoblasts.

Bone samples were analysed from young and old patients, developing a protocol and analysis framework for IMC in bone tissue sections to analyse osteoblasts in-situ for RC deficiency.

Samples from the femoral neck of 10 older healthy volunteers aged 40 – 85 were compared with samples from young patients aged 1-19. We have identified RC complex I defect in osteoblasts from 6 of the older volunteers, complex II defects in 2 of the older volunteers, complex IV defect in just 1 older volunteer, and complex V defect in 4 of the older volunteers.

These observations are consistent with the PolgD257A/D257A mouse-model and suggest that RC deficiency, due to age-related pathogenic mitochondrial DNA mutations, may play a significant role in the pathogenesis of human age-related osteoporosis.
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.

Methods

RF 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.

Results

Among 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.

Conclusions

the 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.
THERMOSENSITIVE HYDROGEL LOADED WITH ENGINEERED ADIPOSE STEM CELLS FOR THE TREATMENT OF DEGENERATIVE INTERVERTEBRAL DISC
Authors: Wu H. , Ding Y. , Sun Y. , Liu Z. , Li C.
Published: July 2023

Intervertebral disc degeneration can lead to physical disability and significant pain, while the present therapeutics still fail to biochemically and biomechanically restore the tissue. Stem cell-based therapy in treating intervertebral disc (IVD) degeneration is promising while transplanting cells alone might not be adequate for effective regeneration. Recently, gene modification and 3D-printing strategies represent promising strategies to enhanced therapeutic efficacy of MSC therapy. In this regard, we hypothesized that the combination of thermosensitive chitosan hydrogel and adipose derived stem cells (ADSCs) engineered with modRNA encoding Interleukin − 4 (IL-4) can inhibit inflammation and promote the regeneration of the degenerative IVD.

Rat ADSCs were acquired from adipose tissue and transfected with modRNAs. First, the kinetics and efficacy of modRNA-mediated gene transfer in mouse ADSCs were analyzed in vitro. Next, we applied an indirect co-culture system to analyze the pro-anabolic potential of IL-4 modRNA engineered ADSCs (named as IL-4-ADSCs) on nucleus pulposus cells.

ModRNA transfected mouse ADSCs with high efficiency and the IL-4 modRNA-transfected ADSCs facilitated burst-like production of bio-functional IL-4 protein. In vitro, IL-4-ADSCs induced increased anabolic markers expression of nucleus pulposus cells in inflammation environment compared to untreated ADSCs.

These findings collectively supported the therapeutic potential of the combination of thermosensitive chitosan hydrogel and IL-4-ADSCs for intervertebral disc degeneration management. Histological and in vivo validation are now being conducted.
INFECTION OUTCOME IN OPEN TIBIAL FRACTURES: A MAJOR TRAUMA CENTRE PERSPECTIVE
Authors: Zhang J. , Lu V. , Zhou A. , Thahir A. , Krkovic M.
Published: July 2023

Open tibial fractures can be difficult to manage, with a range of factors that could affect treatment and outcome. We present a large cohort of patients, and analyse which factors have significant associations with infection outcome. Elucidation will allow clinicians to strive for treatment optimisation, and patients to be advised on likely complications

Open tibia fractures treated at a major trauma centre between 2015-2021 were included. Mean age at injury was 55.4 (range 13-102). Infection status was categorized into no infection, superficial infection, and osteomyelitis.

Age, mode of injury, polytrauma, fibula status, Gustilo-Anderson (GA) classification, wound contamination, time from injury to: first procedure/definitive plastics procedure/definitive fixation, type of definitive fixation, smoking and diabetic status, and BMI, were collected. Multicollinearity was calculated, with highly correlated factors removed. Multinomial logistic regression was performed. Chi Squared testing, with Post Hoc Bonferroni correction was performed for complex categorical factors.

Two hundred forty-four patients with open tibial fractures were included. Forty-five developed superficial infection (18.4%), and thirty-nine developed osteomyelitis (16.0%).

Polytrauma, fibula status, and type of definitive fixation were excluded from the multivariate model due to strong multicollinearity with other variables.

With reference to the non-infected outcome; superficial infection patients had higher BMI (p<0.01), higher GA grade (p<0.01), osteomyelitis patients had longer time to definitive fixation (p=0.049) and time to definitive plastics procedure (p=0.013), higher GA grade (p<0.01), and positive wound contamination(p=0.015).

Poc hoc analysis showed “no infection” was positively associated with GA-I (p=0.029) and GA-II (p<0.01), and negatively associated with GA-IIIC (p<0.01). Osteomyelitis was positively associated with GA-IIIc (p<0.01)

This study investigated the associations between the injury and presentation factors that may affect infection outcome. The variables highlighted are the factors clinicians should give extra consideration to when treating cases, and take preventative measures to optimize treatment and mitigate infection risk.