bluuebunny/crossref_metadata_2025 huggingface dataset:
THE ROLE OF REPEAT POSTOPERATIVE RADIOGRAPHS IN PREDICTING REVISION SURGERY FOLLOWING PRIMARY KNEE ARTHROPLASTY USING MACHINE LEARNING
Authors: Panagiota Glynou S. , Musbahi O. , Cobb J.
Published: November 2024

Introduction

Knee arthroplasty (KA), encompassing Total Knee Replacement (TKR) and Unicompartmental Knee Replacement (UKR), is one of the most common orthopedic procedures, aimed at alleviating severe knee arthritis. Postoperative KA management, especially radiographic imaging, remains a substantial financial burden and lacks standardised protocols for its clinical utility during follow-up.

Method

In this retrospective multicentre cohort study, data were analysed from January 2014 to March 2020 for adult patients undergoing primary KA at Imperial NHS Trust. Patients were followed over a five-year period. Four machine learning models were developed to evaluate if post-operative X-ray frequency can predict revision surgery. The best-performing model was used to assess the risk of revision surgery associated with different number of X-rays.

Result

The study assessed 289 knees with a 2.4% revision rate. The revision group had more X-rays on average than the primary group. The best performing model was Logistic Regression (LR), which indicated that each additional X-ray raised the revision risk by 52% (p<0.001). Notably, having four or more X-rays was linked to a three-fold increase in risk of revision (OR=3.02; p<0.001). Our results align with the literature that immediate post-operative X-rays have limited utility, making the 2nd post-operative X-ray of highest importance in understanding the patient's trajectory. These insights can enhance management by improving risk stratification for patients at higher revision surgery risk. Despite LR being the best-performing model, it is limited by the dataset's significant class imbalance.

Conclusion

X-ray frequency can independently predict revision surgery. This study provides insights that can guide surgeons in evidence-based post-operative decision-making. To use those findings and influence post-operative management, future studies should build on this predictive model by incorporating a more robust dataset, surgical indications, and X-ray findings. This will allow early identification of high-risk patients, allowing for personalised post-operative recommendations.
THE ROLE OF THE PLANTAR FASCIA IN SUPPORTING THE ARCH IN PROGRESSIVE COLLAPSING FOOT DEFORMITY
Authors: Malakoutikhah H. , Madenci E. , Latt D.
Published: November 2024

Introduction

The arch of the foot has been described as a truss where the plantar fascia (PF) acts as the tensile element. Its role in maintaining the arch has likely been underestimated because it only rarely torn in patients with progressive collapsing foot deformity (PCFD). We hypothesized that elongation of the plantar fascia would be a necessary and sufficient precursor of arch collapse.

Method

We used a validated finite element model of the foot reconstructed from CT scan of a female cadaver. Isolated and combined simulated ligament transection models were created for each combination of the ligaments. A collapsed foot model was created by simulated transection of all the arch supporting ligaments and unloading of the posterior tibial tendon. Foot alignment angles, changes in force and displacement within each of the ligaments were compared between the intact, isolated ligament transection, and complete collapse conditions.

Result

Isolated release of the PF did not cause deformity, but lead to increased force in the long (142%) and short plantar (156%), deltoid (45%), and spring ligaments (60%). The PF was the structure most able to prevent arch collapse and played a secondary role in preventing hindfoot valgus and forefoot abduction deformities. Arch collapse was associated with substantial attenuation of the spring (strain= 41%) and interosseous talocalcaneal ligaments (strain= 27%), but only a small amount in the plantar fascia (strain= 10%).

Conclusion

Isolated PF release did not cause arch collapse, but arch collapse could not occur without at least 10% elongation of the PF. Simulated transection of the PF led to substantial increase in the force in the other arch supporting ligaments, putting the foot at risk of arch collapse over time. Chronic degeneration of the PF leading to plantar fasciitis may be an early sign of impending PCFD.
PROGRESSIVE RESISTANCE TRAINING OR NEUROMUSCULAR EXERCISE FOR HIP OSTEOARTHRITIS: A MULTICENTRE CLUSTER RANDOMIZED CONTROLLED TRIAL
Authors: Kjeldsen T. , Thorgaard Skou S. , Dalgas U. , Tønning L. , Birch S. , Frydendal T. , Varnum C. , Garval M. , G Ingwersen K. , Mechlenburg I.
Published: November 2024

Introduction

Exercise is recommended as first-line treatment for patients with hip osteoarthritis (OA). Interestingly, content and dose of exercise interventions seem to be important for the effect of exercise interventions, but the optimal content and dose is unknown. This warrants randomized controlled trials providing evidence for the optimal exercise program in Hip OA. The aim of this trial was to investigate whether progressive resistance training (PRT) is superior to neuromuscular exercise (NEMEX) for improving functional performance, hip pain and hip-related quality of life in patients with hip OA.

Method

This was a multicenter, cluster-randomized, controlled, parallel-group, assessor-blinded, superiority trial. 160 participants with clinically diagnosed hip OA were recruited from hospitals and physiotherapy clinics and randomly assigned to twelve weeks of PRT or NEMEX. The PRT intervention consisted of 5 high-intensity resistance training exercises targeting muscles at the hip and knee joints. The NEMEX intervention included 10 exercises and emphasized sensorimotor control and functional stability. The primary outcome was change in the 30-second chair stand test (30s-CST). Key secondary outcomes were changes in scores on the pain and hip-related quality of life (QoL) subscales of the Hip Disability and Osteoarthritis Outcome Score (HOOS).

Result

The mean changes from baseline to 12-week follow-up in the 30s-CST were 1.5 (95% CI, 0.9 to 2.1) chair stands with PRT and 1.5 (CI, 0.9 to 2.1) chair stands with NEMEX (difference, 0.0 [CI, 0.8 to 0.8] chair stands). For the HOOS pain subscale, mean changes were 8.6 (CI, 5.3 to 11.8) points with PRT and 9.3 (CI, 5.9 to 12.6) points with NEMEX. For the HOOS QoL subscale, mean changes were 8.0 (CI, 4.3 to 11.7) points with PRT and 5.7 (CI, 1.9 to 9.5) points with NEMEX.

Conclusion

In patients with hip OA, PRT is not superior to NEMEX for improving functional performance, hip pain, or hip-related QoL.
CAN PIN SITE INFLAMMATION BE DETECTED WITH THERMOGRAPHIC IMAGING? A CROSS-SECTIONAL MULTICENTRE STUDY OF PATIENTS TREATED WITH EXTERNAL FIXATORS
Authors: Fridberg M. , Rahbek O. , Husum H.-C. , Bafor A. , Duch K. , Iobst C. , Kold S.
Published: November 2024

Introduction

Patients with external fixators are at risk of pin site infection. A more objective assessment of possible pin site infection is warranted, particularly for future home-based monitoring of pin sites. The aim was to determine if thermography can detect signs of inflammation around pin sites by 1) Establishing a maximum temperature cut-off value 2) Investigating the correlation between local temperature and visual signs of inflammation 3) Adjust for anatomical location and ambient room temperature.

Method

This was a cross-sectional international multi-center study following STROBE guidelines. All patients with external ring-fixators scheduled for a visit in the out-patient clinic were eligible. Visual signs of inflammation were categorized using the Modified Gordon classification System (MGS, simplified sMGS). Thermographic imaging was done with an infrared camera (FLIR T540) and the maximum temperature within the ROI (MaxTp) was the primary outcome measure. Sample size and reliability were estimated. Cohen-Kappa, ROC-curve/AUC and Poisson regression were used for statistical analysis.

Result

Data from 1970 pin sites were included. Inter-rater reliability of MGS was Kappa=0.79 and for MaxTp ICC=0.99 (95%CI: 0.99;0.99). Overall, a tendency of rising temperature with increasing sMGS was seen. The difference between sMGS=0 and sMGS>0 was significant. The performance of MaxTp as a screening tool to detect inflammation was reasonable with an AUC of 0.71 (95% CI: 0.65-0.76). The empirically optimal cut-off value was 34.1°C (Sensitivity=65%, Specificity=72%, Positive predictive value=23%, Negative Predictive value=94%). A 1°C increase in MaxTp increased the RR of visual signs of inflammation by a factor 1.5 (95% CI: 1.3; 1.7).

Conclusion

We found a clinical positive association between the temperature at the pin site measured with thermography and visual signs of inflammation. The empirically optimal temperature cut-off value for inflammation screening was 34.1°C. Thermography may be a promising tool for a for a future point of care technology.
FEASIBILITY OF VIRTUAL REALITY IMMERSION IN REDUCING PAIN AND ANXIETY DURING EXTERNAL FIXATOR CARE PROCEDURES
Authors: Bafor A. , Lobst C.
Published: November 2024

Introduction

Previous studies have shown the potential for virtual reality (VR) immersion as a promising technique for pain and anxiety management. The aim of our study was to evaluate the feasibility of VR in the management of pain and anxiety during post-op external fixator care procedures.

Method

This study involved patients aged 5-21 years following limb lengthening/reconstruction surgery with an external fixator. Aqua VR application from the KindVR® was utilized for this study. Subjects were seen during the first four postoperative visits and assigned to a ‘VR-first’ or ‘no-VR-first’ group. Visits alternated between VR immersion and no VR immersion during care procedures. The study endpoints (pain and anxiety levels) were assessed before, during, and after procedures using the Wong-Baker Faces (FACES) and Children's Fear Scale, respectively. Proxy scores for pain and anxiety were also obtained from parents or legal guardians and providers.

Result

A total of 29 patients (16 male and 13 female) were evaluated. The mean age at enrollment was 14.4 ± 2.2 years for group 1 and 14.7 ± 4.0 years for group 2. The median number of pin sites was 7. Anxiety scores were consistently higher during the non-VR immersion experience compared to the VR immersion visits. The pain and anxiety scores were significantly lower in the ‘VR-first’ group during the non-VR immersion study visits compared to patients in the ‘no-VR-first’ group. This observation was also consistent with survey findings among the parent proxies and providers.

Conclusion

VR immersion is associated with lower anxiety scores for pin-site care procedures. VR immersion at the first post-operative visit following limb reconstruction surgery was also associated with lower pain and anxiety scores during subsequent non-VR immersion visits.
PATIENT-SPECIFIC CALIBRATION OF PREOPERATIVE CT SCANS PROVIDE OBJECTIVE CLASSIFICATION OF BONE DENSITY SUBGROUPS FROM PATIENTS UNDERGOING REVERSE SHOULDER ARTHROPLASTY
Authors: Ritter D. , Bachmaier S. , Wijdicks C. , Raiss P.
Published: November 2024

Introduction

The increased prevalence of osteoporosis in the patient population undergoing reverse shoulder arthroplasty (RSA) results in significantly increased complication rates. Mainly demographic and clinical predictors are currently taken into the preoperative assessment for risk stratification without quantification of preoperative computed tomography (CT) data (e.g. bone density). It was hypothesized that preoperative CT bone density measures would provide objective quantification with subsequent classification of the patients’ humeral bone quality.

Methods

Thirteen bone density parameters from 345 preoperative CT scans of a clinical RSA cohort represented the data set in this study. The data set was divided into testing (30%) and training data (70%), latter included an 8-fold cross validation. Variable selection was performed by choosing the variables with the highest descriptive value for each correlation clustered variables. Machine learning models were used to improve the clustering (Hierarchical Ward) and classification (Support Vector Machine (SVM)) of bone densities at risk for complications and were compared to a conventional statistical model (Logistic Regression (LR)).

Results

Clustering partitioned this cohort (training data set) into a high bone density subgroup consisting of 96 patients and a low bone density subgroup consisting of 146 patients. The optimal number of clusters (n = 2) was determined based on optimization metrics. Discrimination of the cross validated classification model showed comparable performance for the training (accuracy=91.2%; AUC=0.967) and testing data (accuracy=90.5 %; AUC=0.958) while outperforming the conventional statistical model (Logistic Regression (LR)). Local interpretable model-agnostic explanations (LIME) were created for each patient to explain how the predicted output was achieved.

Conclusion

The trained and tested model provides preoperative information for surgeons treating patients with potentially poor bone quality. The use of machine learning and patient-specific calibration showed that multiple 3D bone density scores improved accuracy for objective preoperative bone quality assessment.
INTEGRIN Α10Β1-SELECTED HUMAN MESENCHYMAL STEM CELLS CAN DIRECTLY PARTICIPATE IN CARTILAGE REGENERATION AND HAVE IMMUNOMODULATORY CAPACITIES
Authors: Uvebrant K. , Andersen C. , Lim H. C. , Vonk L. , Åkerlund E. L.
Published: November 2024

Introduction

Homogenous and consistent preparations of mesenchymal stem cells (MSCs) can be acquired by selecting them for integrin α10β1 (integrin a10-MSCs). Safety and efficacy of intra-articular injection of allogeneic integrin a10-MSCs were shown in two post-traumatic osteoarthritis horse studies. The current study investigated immunomodulatory capacities of human integrin a10-MSCs in vitro and their cell fait after intra-articular injection in rabbits.

Method

The concentration of produced immunomodulatory factors was measured after licensing integrin a10-MSCs with pro-inflammatory cytokines. Suppression of T-cell proliferation was determined in co-cultures with carboxyfluorescein N-succinimidyl ester (CFSE) labelled human peripheral blood mononuclear cells (PBMCs) stimulated with anti-CD3/CD28 and measuring the CFSE intensity of CD4+ cells. Macrophage polarization was assessed in co-cultures with differentiated THP-1 cells stimulated with lipopolysaccharide and analysing the M2 macrophage cell surface markers CD163 and CD206. In vivo homing and regeneration were investigated by injecting superparamagnetic iron oxide nanoparticles conjugated with Rhodamine B-labeled human integrin a10-MSCs in rabbits with experimental osteochondral defects. MSC distribution in the joint was followed by MRI and fluorescence microscopy.

Result

The production of the immunomodulatory factors indoleamine 2,3-dioxygenase and prostaglandin E2 was increased after inflammatory licensing integrin a10-MSCs. Co-cultures with integrin a10-MSCs suppressed T-cell proliferation and increased the frequency of M2 macrophages. In vivo injected integrin a10-MSCs homed to osteochondral defects and were detected in the repair tissue of the defects up to 10 days after injection, colocalized with aggrecan and type II collagen.

Conclusion

This study showed that human integrin a10-MSCs have immunomodulatory capacities and in vivo can home to the site of osteochondral damage and directly participate in cartilage regeneration. This suggests that human integrin α10β1-selected MSCs may be a promising therapy for osteoarthritis with dual mechanisms of action consisting of immunomodulation and homing to damage followed by early engraftment and differentiation into chondrocyte-like cells that deposit hyaline cartilage matrix molecules.
MULTIFACTORIAL BIOENGINEERING TO CONTROL CELL FATE
Authors: Zevgolis D.
Published: November 2024

Introduction

Bereft of their optimal tissue context, cells lose their phenotype, function and therapeutic potential during in vitro culture. Despite the fact that in vivo cells are exposed simultaneously to multiple signals, traditional ex vivo cultures are monofactorial. With these in mind, herein we assessed the combined effect of surface topography, substrate rigidity, collagen type I coating and macromolecular crowding in human tenocyte, skin fibroblast and bone marrow mesenchymal stromal cell cultures.

Methods

Thermal imprinted was used to pattern (groove depth: 2,000 nm, groove width: 2,000 nm, line width: 2,000 nm) polydimethylsiloxane substrates of different rigidity (50 kPa, 130 kPa, 1,000 kPa). Grooved and planar substrates were subsequently coated with collagen type I and used to culture the aforementioned cell populations without and with macromolecular crowding (100 μg/ml carrageenan). After 3, 7 and 14 days in culture, cell morphology, viability, metabolic activity, proliferation, protein synthesis and deposition and gene expression analyses were conducted.

Results

None of the variables assessed affected cell viability, metabolic activity and proliferation. Surface topography was found to be a potent regulator of cell morphology. Macromolecular crowding significantly increased extracellular matrix deposition, albeit in globular manner independently on whether grooved or planar substrates were used, possibly due to the low dimensionality of the grooves. Gene expression analysis made apparent that the 130 kPa and the 1,000 kPa grooved substrates under macromolecular crowding conditions maintained human tenocyte phenotype and directed human bone marrow mesenchymal stromal cells towards tendon-like lineage, respectively. None of the conditions assessed dramatically affected human skin fibroblast fate.

Conclusions

Collectively, our data indicate that the physicochemical in vitro microenvironment modulators assessed herein are capable of maintaining human tenocyte phenotype and differentiating human bone marrow mesenchymal stromal cells towards tenogenic lineage, but not in trans-differentiating human skin fibroblasts.
MICROSTRUCTURAL AND TRANSCRIPTOMIC ANALYSIS OF TRABECULAR BONE IN PATIENTS WITH IDIOPATHIC OSTEONECROSIS OF THE FEMORAL HEAD
Authors: Quero L. S. , Duch C. E. , Vilaboa Díaz N. , Rey E. G.
Published: November 2024

Introduction

The most frequent diagnosis in young adults undergoing total hip arthroplasty (THA) is osteonecrosis of the femoral head (ONFH), an evolving and disabling condition with an increasing prevalence worldwide. Treatment of ONFH remains a challenge mainly because of a lack of understanding of the disease's pathophysiological basis. This study investigated the biological processes that could be affected by ONFH by comparing the microstructure, histological characteristics and transcriptomic profile of trabecular bone from the femoral head (FH) and the intertrochanteric region (IT) of patients suffering from this condition.

Method

A total of 18 patients with idiopathic ONFH undergoing THA in our institution were included. Trabecular bone explants were taken intraoperatively from the FH and the IT of patients. Bone microstructure was examined by micro-computed tomography (micro-CT). After bone sectioning, histological features were studied by hematoxylin and eosin staining. Differential gene expression was investigated using a microarray platform.

Result

Micro-CT imaging showed higher trabecular separation and lower trabecular thickness and bone volume in trabecular bone from the FH than from the IT. Histological staining revealed that the number of osteoblasts on the bone surface and the percentage of empty lacunae were higher in trabecular bone from the FH. Transcriptome analysis identified a differential signature in trabecular bone from the FH compared to the IT. The gene ontology analyses of the genes overexpressed in trabecular bone from the FH revealed a range of enriched biological processes related to cell division and immune response. In contrast, most downregulated transcripts were involved in bone formation.

Conclusion

This study identified changes in the microarchitecture, histological features and transcriptomic signature of trabecular bone from the FH of patients with idiopathic ONFH, which might underlie the pathophysiology of this condition. This work was supported by PI22/00939 grant from ISCIII-FEDER-MICINN-AES and Luis Alvarez grant from IdiPAZ.
RETURN TO SPORT AMONG 1,926 PATIENTS WITH HIP DYSPLASIA AFTER UNDERGOING PERIACETABULAR OSTEOTOMY
Authors: Tønning L. , Jakobsen S. S. , Kemp J. , O’Brien M. , Dalgas U. , Mechlenburg I.
Published: November 2024

Introduction

Symptomatic hip dysplasia is often treated with periacetabular osteotomy (PAO). Studies investigating the effect of PAO have primarily focused on radiographic measurements, pain-related outcomes, and hip survival whereas evidence related to sport participation is limited.

Methods

All patients in our institutional database were deemed eligible for this cohort study if they underwent PAO and had answered at least one question related to sport participation. Patients were asked if they were playing sport preoperatively, 6 months after PAO as well as 2, 5, 10, 15 and 20 years after. In addition, patients were asked if they were able to play their preferred sport, what type and at what level they were playing sport, and if surgery had improved their sport performance.

Results

Among 2398 patients surveyed, 1926 (80%) were included and 56% were playing sport 6 months after PAO. This number was 61% two years after PAO, and remained around that for the following years, before dropping 15 years after PAO. Between 56% and 71% of patients felt that their sporting performance improved following PAO at the different time points. Between 39% (6 months after PAO) and 63% (15 years after PAO) were able to participate in their preferred sport.

Conclusion

The majority of patients undergoing PAO due to hip dysplasia will return to, and maintain, sport after PAO. More than half of patients undergoing PAO believe that the surgery improved their sports performance, and long after the surgery more than half of patients undergoing PAO are able to play their preferred sport.
ADOLESCENT PORCINE STIFLE JOINT AS A MODEL FOR ACL BIOMECHANICS: EFFECTS OF AXIAL AND TORSIONAL LOADS
Authors: Koh J. , Mungalpara N. , Chang N. , Devi I. M. P. , Hutchinson M. , Amirouche F.
Published: November 2024

Introduction

Understanding knee joint biomechanics is crucial, but studying Anterior cruciate ligament (ACL) biomechanics in human adolescents is challenging due to limited availability cadaveric specimens. This study aims to validate the adolescent porcine stifle joint as a model for ACL studies by examining the ACL's behavior under axial and torsion loads and assessing its deformation rate, stiffness, and load-to-failure.

Methods

Human knee load during high-intensity sports can reach 5-6 times body weight. Based on these benchmarks, the study applied a force equivalent to 5-times body weight of juvenile porcine samples (90 pounds), estimating a force of 520N. Experiments involved 30 fresh porcine stifle joints (Yorkshire breed, Avg 90 lbs, 2-4 months old) stored at -22°C, then thawed and prepared. Joints were divided into three groups: control (load-to-failure test), axially loaded, and 30-degree torsion loaded. Using a servo-hydraulic material testing machine, the tibia's longitudinal axis was aligned with the load sensor, and specimens underwent unidirectional tensile loading at 1 mm/sec until rupture. Data on load and displacement were captured at 100 Hz.

Results

One-way ANOVA showed statistically significant differences in maximum failure force among loading conditions (p = 0.0039). Post hoc analysis indicated significant differences between the control and 500N (non-twisted) groups (p = 0.014) and between the control and 500N (twisted) groups (p = 0.003). However, no significant difference was found between 500N (non-twisted) and 500N (twisted) groups (p = 0.2645). Two samples broke from the distal femur growth plates, indicating potential growth plate vulnerability in adolescent porcines.

Conclusions

The study validates the adolescent porcine stifle joint as a suitable model for ACL biomechanical research, demonstrating that torsional loads are as damaging to the ACL's integrity as equivalent axial loads. It also highlights the potential vulnerability of growth plates in younger populations, reflected in the porcine model.
IMPROVED HUMAN TENOCYTE VIABILITY BY APPLYING PHYSIOLOGICALLY RELEVANT MECHANICAL LOADS IN A PERFUSION BIOREACTOR SYSTEM
Authors: Machain T. C. , Kharchenko A. , Hostettler R. , Lippl J. , Mouthuy P. A.
Published: November 2024

Introduction

Supraspinatus tears comprise most rotator cuff injuries, the leading cause of shoulder pain and an increasing problem with ageing populations. Surgical repair of considerable or persistent damages is customary, although not invariably successful. Tissue engineering presents a promising alternative to generate functional tissue constructs with improved healing capacities. This study explores tendon tissue constructs’ culture in a platform providing physiological mechanical stimulation and reports on the effect of different loading regimes on the viability of human tendon cells.

Method

Porcine decellularized tendon scaffolds were fixed into flexible, self-contained bioreactor chambers, seeded with human tenocytes, allocated in triplicates to either static control, low (15±0.8Newtons [N]), medium (26±0.5N), or high (49±2.1N)-force-regime groups, connected to a perfusion system and cultured under standard conditions. A humanoid robotic arm provided 30-minute adduction/abduction stimulation to chambers daily over a week. A metabolic activity assay served to assess cell viability at four time points. Statistical significance = p<0.05.

Result

One day after beginning mechanical stimulation, chambers in the medium and high-force regimes displayed a rise in metabolic activity by 3% and 5%, respectively. By the last experimental day, all mechanical stimulation regimes had induced an augment in cell viability (15%, 57% and 39% with low, medium, and high loads, respectively) matched against the static controls. Compared to all other conditions, the medium-force regime prompted an increased relative change in metabolic activity for every time point set against day one (p<0.05).

Conclusion

Human tenocytes’ viability reflected by metabolic activity in a physiologically relevant bioreactor system is enhanced by loading forces around 25N when mechanically stimulating using adduction/abduction motions. Knowing the most favourable load regime to stimulate tenocyte growth has informed the ongoing exploration of the distinctive effect of different motions on tendon regeneration towards engineering tissue grafts. This work was supported by the Engineering and Physical Sciences Research Council EP/S003509/1.
CHARACTERIZING THE SURFACE DEGRADATION OF OSTEOARTHRITIC CARTILAGE BASED ON RAMAN SPECTROSCOPY AND INVESTIGATING ITS MECHANO-TRIBOLOGICAL PROPERTIES
Authors: Mahadeshwara M. R. , Pandit H. , Hall R. M. , Jawad M. A. , Bryant M. , Gendy R. E.
Published: November 2024

Introduction

Osteoarthritis (OA) occurs due to a multi-scale degradation of articular cartilage (AC) surface which aggravates the disease condition. Investigating the micro-scale structural alterations and mechano-tribological properties facilitates comprehension of disease-mechanisms to improve future injectable-therapies. This study aims to analyze these properties using various experimental and analytical methods to establish correlations between their morpho-physiological features.

Method

In this study, Raman-spectroscopy was used to investigate microscale changes in AC constituents and categorize OA damage regions in knee-joint samples from joint replacement patients (Samples = 5 and Regions = 40). Following, microscale indentation and sliding tests were performed on these regions to evaluate variations in aggregate-modulus (AM) and elastic-modulus (EM), with coefficient of friction (COF). Finally, scanning electron microscopy (SEM) was employed to analyze these morphological variations.

Result

Raman spectroscopy revealed degree of collagen-damage (Amide-3 α-helix to random-coil ratio I-1250/I-1280), proteoglycan-damage (Sulphated bonds SO3- to CH2 twist ratio I-1065/I-1206), amount of bone exposure (Phosphated-hydroxyapatite PO43- to Amide-1 ratio I-959/I-1669) and increased crystallinity (Carbonated hydroxyapatite CO32- to Amide-1 ratio I-1075/I-959) in ECM. Subsequently, these regions were categorized into different groups (G) based on these damages; G1 (Proteoglycan); G2 (Collagen + Proteoglycan); G3 (Collagen + Proteoglycan + Carbonated crystallinity) G4 (Collagen or Proteoglycan + bone exposure); and G5 (Collagen + Proteoglycan + Bone exposure). Further experimentation revealed the differences in mechano-tribological properties (AM, EM, and COF) between the different groups. G5 displayed the highest values of AM (1.5 ± 0.2MPa), EM (0.3 ± 0.01MPa) and COF (0.39 ± 0.08), compared to other groups. These altered properties were confirmed via SEM that revealed micro-asperity junctions, superficial fronding, fibrillations and bone exposure at these damaged regions.

Conclusion

This study demonstrated micro-scale changes in AC among OA patients commensurate to the degree of tissue damage, which correlates with disease progression altering joint structure and function particularly in regions with high COF.
IN VITRO CO-CULTURE OF TISSUE-ENGINEERED MINERALIZED CARTILAGE AND VESSEL NETWORKS TO MODEL ENDOCHONDRAL OSSIFICATION
Authors: Ji E. , Leijsten L. , Bouma J. W. , Rouchon A. , Maggio N. D. , Banfi A. , Osch G. V. , Farrell E. , lolli A.
Published: November 2024

Introduction

Endochondral ossification (EO) is the process of bone development via a cartilage template. It involves multiple stages, including chondrogenesis, mineralisation and angiogenesis. Importantly, how cartilage mineralisation affects angiogenesis during EO is not fully understood. Here we aimed to develop a new in vitro co-culture model to recapitulate and study the interaction between mineralised cartilage generated from human mesenchymal stromal cells (hMSCs) and microvascular networks.

Method

Chondrogenic hMSC pellets were generated by culture with transforming growth factor (TGF)-β3. For mineralised pellets, β-glycerophosphate (BGP) was added from day 7 and TGF-β3 was withdrawn on day 14. Conditioned medium (CM) from the pellets was used to evaluate the effect on human umbilical vein endothelial cells (HUVECs) in migration, proliferation and tube formation assays. To perform direct co-cultures, pellets were embedded in fibrin hydrogels containing vessel-forming cells (HUVECs, adipose stromal cells) for 10 days with BGP to induce mineralisation. The pellets and hydrogels were characterised by immunohistochemistry and confocal imaging.

Result

The CM from d14 chondrogenic or mineralised pellets significantly stimulated HUVEC migration and proliferation, as well as in vitro vascular network formation. When CM from pellets subjected to prolonged mineralisation (d28) was used, these effects were strongly reduced. When chondrogenic and mineralised pellets were directly co-cultured with vessel-forming cells in fibrin hydrogels, the cartilage matrix (collagen type II/X stainings) and the mineral deposition (von Kossa staining) were well preserved. Confocal imaging analyses demonstrated the formation of microvascular networks with well-formed lumina. Importantly, more microvascular structures were formed in the proximity of chondrogenic pellets than mineralized pellets.

Conclusion

The angiogenic properties of tissue engineered cartilage are significantly reduced upon prolonged mineralisation. We developed a 3D co-culture model to study the role of angiogenesis in endochondral bone formation, which can have applications in disease modelling studies.
PIEZO1 AS A MEDIATOR OF CHONDROCYTE NUCLEAR MECHANICS AND CHROMATIN METHYLATION STATE
Authors: Castorena J. G. , Riester R. , Ornelas M. G. , Guilak F. , Danalache M.
Published: November 2024

Introduction

Piezo1 is a mechanosensitive Ca2+ ion channel that has been shown to transduce hyper-physiologic mechanical loads in chondrocytes. In osteoarthritic cartilage, Piezo1 expression was shown to be upregulated by interleukin-1 alpha (IL-1α) and resulted in altered calcium dynamics and actin cytoskeleton rarefication. Together these studies highlight the importance of Piezo1 channels during joint injury. However, the mechanism by which Piezo1 regulates chondrocyte physiology and mechanotransduction during homeostasis is still largely unknown. In this study, we investigate the impact of Piezo1 activation on nuclear mechanics and chromatin methylation state.

Methods

Porcine chondrocytes (n=3-5 pigs) were treated with Yoda1, a Piezo1-specific agonist, for either 2, 5, 15 or 180 minutes. To characterize chromatin state, we monitored the abundance of a chromatin methylation marker (H3K9Me3) using immunofluorescence (IF). Atomic force microscopy (AFM, 25 nm cantilever) was employed to quantify the nuclear elastic modulus (NEM) of individual cell nuclei. To explore the interplay between cytoskeletal dynamics and nuclear mechanics, chondrocytes were treated with Latrunculin A (LatA), an actin polymerization inhibitor.

Result

IF experiments showed chromatin methylation was the lowest 2 minutes post Yoda1 activation of Piezo1 (p=0.027). Additionally, we found that 2 or 5 minutes post-Piezo1 activation resulted in a significantly lower NEM when compared to the control (p<0.00001). The observed decrease in NEM at 2 and 5 minutes post-Piezo1 activation was not observed after knocking down Piezo1 (p>0.99). In LatA treated cells, the elevated NEM persisted even after Piezo1 activation with Yoda1 (p>0.75).

Conclusion

These findings illuminate the mechanism by which Piezo1 activation and actin remodeling regulate transient mechanotransduction during homeostasis. Further research into the transient decrease in nuclear stiffness and chromatin methylation observed during the initial 5 minutes of Piezo1-induced Ca2+ signaling, may contribute to a better understanding of the role of Piezo1 channels in joint injury and development of therapeutic interventions for osteoarthritis.
RISK FACTORS FOR DEVELOPMENTAL DYSPLASIA OF THE HIP AT THREE MONTHS OF AGE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Tirta M. , Rahbek O. , Kold S. , Husum H. C.
Published: November 2024

Introduction

Selective screening of children at risk for developmental dysplasia of the hip (DDH) is based on clinical examination and risk factor identification. Two meta-analyses published in 2012 found breech presentation, family history of DDH, female sex and primiparity to increase the risk of DDH. However, the DDH definition, reference tests and age of the examined children vary considerably, complicating the translation of those findings to current screening guidelines. The aim of this meta-analysis was to evaluate the association of previously proposed risk factors to the risk of sonographically verified DDH.

Method

We searched PubMed, EMBASE and Cochrane library to identify cohort, RCTs, case-control and cross-sectional studies from 1980 to 2023 in English language. Eligible studies included participants under three months of age, where the diagnosis of DDH was made by hip ultrasound using the gold standard Graf method and reported information on one or more of the proposed risk factors and final diagnosis was available.

Result

Of 5363 studies screened, 20 studies (n=64543 children) were included. Breech presentation (OR: 4.2, 95%CI 2.6-6.6), family history (3.8, 95%CI 2.1-7.2), female sex (2.5, 95%CI 1.7-3.6), oligohydramnios (3.8, 95%CI 1.7-8.5) and high birthweight (2.0, 95%CI 1.6-2.5) significantly increased the risk of DDH. C-section, primiparity, multiple births, low birthweight and prematurity were not found to increase the risk for DDH, and there was only one study about clubfoot as a risk factor. Heterogeneity was high (I2>75%) in all the tested factors except high birthweight (I2=0%). Subgroup analysis was performed to investigate these heterogeneities.

Conclusion

Family history of DDH and breech presentation are associated with significant increase of the risk of sonographic DDH in children aged three months. A similar risk increase was detected for oligohydramnios, which was not detected in previous meta-analyses. Additionally, the DDH risk increase of female sex was found to be lower than previously reported.
RISKS FOR REOPERATION TO PROMOTE UNION IN PERIPROSTHETIC DISTAL FEMUR FRACTURES
Authors: Schlauch A. , Shah I. , Crawford B. , Martin A. , Denisov A , Tamer P. , Farrell B.
Published: November 2024

Introduction

Distal femur fractures around a total knee arthroplasty (TKA) are a growing problem for orthopaedic surgeons. The purpose of this study was to identify risks of reoperation for nonunion following open reduction and internal fixation of TKA periprosthetic distal femur fractures (PDFF).

Method

Patients with PDFF (AO 33A-C[VB1, C1, D1], Su types 1-3) managed operatively with open reduction and internal fixation (ORIF) were retrospectively reviewed. Exclusion criteria were acute management with a distal femur replacement, less than 6 months of follow-up, and lack of injury or follow-up radiographs. The primary outcome measure was reoperation to achieve bony union. Comparisons were made between cases that did and did not require a reoperation to achieve union. Univariate analysis was used to identify factors to be analyzed in multivariate analysis to determine independent risk factors for the primary outcome.

Result

A total of 77 patients met inclusion criteria. Union rate was 69/77 (89.6%). There were no differences between the groups for age, sex, BMI, comorbidities, Su classification, open injury, or mechanism of injury. Multivariate analysis identified risks for nonunion including post-operative malalignment (OR 1.41; CI 1.20-1.64; p<0.001), notching pre-operatively (OR 1.22; CI 1.04-1.42; p=0.012), presence of screws through fracture line (OR 1.28; CI 1.17-1.39; p<0.001), plate length <12 holes (OR 1.16; CI 1.02-1.33; p=0.024) and screw density greater than 0.4 (OR 2.18; CI 1.25-3.78; p=0.006)

Conclusion

The reoperation rate to promote union was 10.4%. The study identified post-operative malalignment, notching pre-operatively, presence of screws through fracture line, plate length <12 holes, and proximal screw density greater than 40% as independent risk factors for nonunion.
INITIAL CONSTRUCT STABILITY OF LONG CEPHALOMEDULLARY NAILS WITH CONVENTIONAL DISTAL LOCKING COMPARED TO SIMILAR NAILS WITH SUPERIOR LOCKING FOR COMPLEX TROCHANTERIC FRACTURES AO31-A2.2: A BIOMECHANICAL STUDY
Authors: Schulz A. P. , Münch M. , Barth T. , Frese J. , Hinz N. , Hartel M.
Published: November 2024

Introduction

A long nail is often recommended for treatment of complex trochanteric fractures but requires longer surgical and fluoroscopy times. A possible solution could be a nail with an appropriate length which can be locked in a minimally invasive manner by the main aiming device. We aimed to determine if such a nail model* offers similar structural stability on biomechanical testing on artificial bone as a standard long nail when used to treat complex trochanteric fractures.

Method

An artificial osteoporotic bone model was chosen. As osteosynthesis material two cephalomedullary nails (CMN) were chosen: a superior locking nail (SL-Nail) which can be implanted with a singular targeting device, and a long nail (long-nail) with distal locking using free-hand technique. AO31-A2.2 fractures were simulated in a standardized manner. The insertion of the nail was strictly in accordance with the IFU and surgical manual of the manufacturer. The nail was locked dynamically proximally and statically distally. Axial height of the construct, varus collapse, and rotational deformity directly after nail insertion were simulated. A Universal Testing Machine was used. Measurements were made with a stereo-optic tracking system. Reactive movements were recorded and evaluated in all six degrees of freedom. A comparative analysis provided information about the stability and deformation of the assemblies to be compared.

Result

There was a detectable difference in the axial fracture movement resulting in narrowing of the fracture gap. The load displacement was 1.7mm higher for the SL-Nail. There was no difference in varus collapse or rotational deformity between the nail variants.

Conclusion

We conclude that there are small differences which are clinically insignificant and that a superior locking nail can safely be used to manage complex trochanteric fractures.

*DCN SL nail, SWEMAC, Linköping, Sweden

Funding: no funding
LONG-TERM OUTCOMES FOLLOWING TUMOUR RESECTION AND VASCULARIZED FIBULAR GRAFTING IN DENMARK
Authors: Nielsen C. L.
Published: November 2024

Introduction

Vascularized fibular grafting following tumor resection is an essential treatment option in limb salvage surgery. This study aimed to assess the surgical and oncological outcomes of patients treated in Denmark between 2010 and 2022.

Method

We present a retrospective review of a national cohort comprising 27 patients. The indications were 13 cases of Ewing sarcoma, 12 cases of osteosarcoma, and 2 cases of giant cell tumor. The median age at surgery was 16 years (range: 2-39), and the median follow-up was 82 months (range: 12-138). Patients were analyzed overall and stratified into upper and lower extremity groups based on tumor location.

Result

The primary rate of graft union was 63%, and after secondary procedures, the overall rate of graft union was 67%, with a median time to union of 13 months (range: 7-29). The reoperation rate was 74%, while the rate of limb salvage was 93%, with two patients undergoing amputation during follow-up. The 5-year overall survival rate was 81% (95% CI: 61-92). Patients with upper extremity tumors were more likely to attain graft union (92% vs. 47%, p=0.02) and less likely to undergo multiple reoperations (17% vs 60%, p=0.047) compared to patients with lower extremity tumors.

Conclusion

Vascularized fibula grafting remains a valuable option in limb salvage surgery with acceptable long-term outcomes. However, especially in lower extremity cases, a low rate of graft union and multiple reoperations are to be expected.
Head-mounted displays based on human eye condition variation patterns
Authors: Cao Tuo , Wang Lingyun , Yan Shenghu , Gong Shijie
Published: November 2024

In response to the practical demands for a wide field of view (FOV), long exit pupil distance, and high image quality in head-mounted displays, an initial structure was built based on the principles of catadioptric lenses in a folded optical path (pancake optics) and the field curvature correction formula. Subsequently, using even-order aspheric surfaces, a VR optical system was developed with a FOV of 2w=110∘, an exit pupil distance of 15 mm, and an exit pupil diameter of 8 mm. Compared to traditional designs, a human eye model was introduced as the image plane to construct a VR–human eye optical system analysis model, allowing for direct analysis of the retinal image quality under different states of the human eye. After that, based on medical statistical data, the impact of different light intensity conditions on the retinal image quality of the VR optical system was explored. Experimental results showed that changes in light intensity affect the pupil diameter, which, in turn, influences the final image quality of the system. To solve the issues, two solutions were proposed: adjusting the screen distance and changing the lens spacing. Both methods significantly improved the imaging quality on the human retina, with an increase of over 30% in the average MTF value. A comparison of these methods was conducted, providing valuable references for future VR optical system designs.
Evaluation of the Sagnac-loop laser frequency stabilization to sub-Doppler spectral lines: erratum
Authors: Hasegawa Taro
Published: November 2024

This erratum gives corrections for the errors in a previously published paper [J. Opt. Soc. Am. B 40, 667 (2023)JOBPDE0740-322410.1364/JOSAB.482223].
Light transport in turbid water for 3D underwater imaging
Authors: Thorstensen Jostein , Zonetti Simone , Thielemann Jens
Published: November 2024

In this work, we have investigated the properties of light transport in turbid water for underwater 3D imaging, by comparing literature, simulations, and experiments. The work is motivated by a need for high-quality 3D image data for underwater robotics, also in turbid waters. We present a comparative analysis of how sine wave and line patterns degrade upon propagation through turbid water, and explain the difference in degradation through analysis of the signal response of the water. We find that line patterns provide a sharp signal peak from the un-scattered (ballistic) photons, with a very broad skirt of scattered signal. The detection of the un-scattered peak allows for sub-millimeter 3D reconstruction quality at water turbidities up to 4.8 NTU (nephelometric turbidity units). Using sine waves, 3D precision rapidly drops, as the scattered signal from large parts of the scene causes rapid loss of signal contrast. 3D reconstruction fails at turbidities above 3.1 NTU. In dark parts of the scene, both signal types yield incorrect 3D reconstruction, as forward scattered signal from surrounding brighter regions dominate over the correct signal peak. In line with literature on scattering properties of water, we find that the use of long wavelengths (red signal) gives less scattering and higher signal contrast compared with the use of green and blue, thereby providing lower 3D noise.
Experimental investigation of heralded Gaussification of phase-randomized coherent states of light
Authors: Dostál Martin , Ježek Miroslav , Fiurášek Jaromír , Bílek Jan
Published: November 2024

Probabilistic heralded Gaussification of quantum states of light is an important ingredient of protocols for distillation of continuous variable entanglement and squeezing. An elementary step of the heralded Gaussification protocol consists of interference of two copies of the state at a balanced beam splitter, followed by conditioning on the outcome of a suitable Gaussian quantum measurement on one output mode. When iterated, the protocol either converges to a Gaussian state or diverges. Here, we report on experimental investigation of the convergence properties of iterative heralded Gaussification. We experimentally implement two iterations of the protocol, which requires simultaneous processing of four copies of the input state. We utilize the phase-randomized coherent states as the input states, which greatly facilitates the experiment because these states can be generated deterministically, and their mean photon number can easily be tuned. We comprehensively characterize the input and partially Gaussified states by balanced homodyne detection and quantum state tomography. Our experimental results are in good agreement with theoretical predictions and they provide new insights into the convergence properties of heralded quantum Gaussification.
Fast demodulation algorithm implementation in OFDR with wavelength selection matching and local cross-correlation
Authors: Wang Yifan , Gu Xueliang , Wang Haomao , Liu Youze , Zhou Rui , Zhang Wei , Peng Xin , Zhang Zhiguo
Published: November 2024

Optical frequency domain reflectometry (OFDR) is widely used in various fields. This paper presents an optimized wavelength selection matching (WSM) and local cross-correlation (LCC) technique for real-time strain monitoring based on OFDR. WSM is employed to extract waveform features and identify suspected strain locations. LCC is used to calculate the strain at these suspected locations to obtain accurate results. According to the results, with the optimized method, the strain localization error is below 0.02% in various situations. Meanwhile, the demodulation speed outperforms traditional algorithms in all aspects.