Fracture Site Research Articles

Prevalence of vertebral fractures at death

Abstract Introduction Despite many studies on the prevalence of vertebral fractures (VFs), the VF prevalence at death in the Japanese population remains unclear. Materials and methods We evaluated the VF prevalence at death in a Japanese cohort using autopsy imaging computed tomography (AiCT). We enrolled 365 cadavers (188 men, 177 women, mean age of 84.6 years) donated for anatomical dissection at Shimane University School of Medicine. The VFs were diagnosed using the semiquantitative technique of Genant from the first cervical vertebra to the fifth lumbar vertebra. Results The overall VF prevalence was 69.6% (58.5%/81.4% in men/women), of which 46.0% (29.8%/63.3% in men/women) had thoracic VFs, and 58.1% (50.5%/66.1% in men/women) had lumbar VFs. The most frequent fracture site was lumbar spine 1 (L1) with 31.5% (22.9%/40.7% in men/women), followed by thoracic spine 12 (T12) with 31.0% (20.7%/41.8% in men/women). In terms of severity, 3.8% (4.8%/2.8% in men/women), 23.8% (27.1%/20.3% in men/women), and 41.9% (26.6%/58.2% in men/women) were Grades 1, 2, and 3. The VFs from T3 to L5 and of Grade 3 severity were significantly higher in women. VF and Grade 3 fractures were associated with a history of surgical intervention for femoral neck fractures. VFs were not associated with the following underlying causes of death: cancer, heart disease, senile death, cerebrovascular disease, pneumonia, and aspiration pneumonia. Conclusion The VF prevalence at death, assessed by AiCT in cadavers donated for anatomical dissection, was higher in both men and women compared with previous studies conducted on individuals aged ≥ 80 years in Japan.

Age-stratified anatomical differences of orbital floor and medial orbital wall blowout fractures.

To define the anatomical variance between orbital floor and medial orbital wall blowout fractures, and its change with age. This was a retrospective, observational study analyzing data from 557 patients with isolated blowout fractures of the orbital floor or medial orbital wall. Axial and quasi-sagittal CT images were analyzed to compare radiologic data on orbital wall morphology between fracture site groups and among age groups. Patient ages were classified as: 0-9 (childhood), 10-18 (adolescence), 19-44 (early adulthood), 45-64 (middle adulthood), and ≥ 65 years (late adulthood). The orbital floor fracture group demonstrated significantly steeper orbital floors (p < 0.001), while the medial wall fracture group exhibited a tendency for more convex medial orbital walls (p = 0.066). Among age groups, medial wall fracture was predominant in the late adulthood group only (p < 0.001). Patients in the childhood and late adulthood groups had significantly flatter orbital floors (p < 0.001). Patients in the childhood group presented with a concave medial orbital wall (p < 0.001). The anteroposterior length of the medial orbital wall and the number of ethmoid air cells were not different between fracture groups (p = 0.603 and0.753, respectively) and among age groups (p = 0.306 and0.456, respectively). Patients with orbital floor and medial orbital wall fractures had anatomically steeper orbital floors and convex medial orbital walls, respectively. Age-related differences in the shape of the orbital walls may influence variation in orbital blowout fracture sites by age. WHAT IS KNOWN : Fracture sites of the orbital walls differ according to age groups. The floor is morecommonly fractured in children, with a shift to the medial wall in the elderly. Orbital floor and medial orbital wall fractures present with anatomically higher floor and medial walls, respectively, compared to each other. This indicates steeper convexities of the walls which predispose them to fracturing. Children's medial orbital walls are initially concave, then shift to convex structures with facial bone and sinus maturation. This explains why there is a change in blowout fracture site between age groups, as it has been documented that concave structures are more resistant to deformation.

Methylglyoxal compromises callus mineralization and impairs fracture healing through suppression of osteoblast terminal differentiation.

Impaired fracture healing in diabetic patients leads to prolonged morbidity and increased healthcare costs. Methylglyoxal (MG), a reactive metabolite elevated in diabetes, is implicated in various complications, but its direct impact on bone healing remains unclear. Here, using a non-diabetic murine tibial fracture model, we demonstrate that MG directly impairs fracture healing. Micro-computed tomography revealed decreased volumetric bone mineral density in the callus, while callus volume remained unchanged, resulting in a brittle bone structure. This was accompanied by reduced expression of osteocalcin and bone sialoprotein, both critical for mineralization. Biomechanical analysis indicated that MG reduced the mechanical resilience of the fracture site without altering its elastic strength, suggesting that the impairment was not primarily due to the accumulation of advanced glycation end-products in the bone extracellular matrix. In vitro studies confirmed that non-cytotoxic concentrations of MG inhibited osteoblast maturation and mineralization. Transcriptomic analysis identified downregulation of Osterix, a key transcription factor for osteoblast maturation, without altering Runx2 levels, leading to decreased expression of key mineralization-related factors like osteocalcin. These findings align with clinical observations of reduced circulating osteocalcin levels in diabetic patients, suggesting that the detrimental effects of MG on osteoblasts may extend beyond bone metabolism. Our study highlights MG and MG-sensitive pathways as potential therapeutic targets for improving bone repair in individuals with diabetes and other conditions characterized by elevated MG levels.

The Role of Mindfulness Decompression Therapy in Managing Acute Stress Disorder in Traumatic Fracture Patients.

Traumatic fractures are common orthopedic injuries with higher incidence globally, leading to acute stress disorder (ASD). Therefore, this study aimed to analyze the clinical outcomes of mindfulness-based stress reduction (MBSR) therapy in patients with traumatic bone fractures suffering from ASD. This study included 135 patients who underwent trauma and fracture treatment at The 305th Hospital of the PLA between August 2021 and August 2023. Based on their participation in MBSR therapy, they were categorized into a conventional group (n = 62) and a combined group (n = 73). We comparatively analyzed the ASD Scale (ASDS), Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Self-Rating Sleep Status Scale (SRSS), and World Health Organization Quality of Life (WHOQOL) measurement-BREF (WHOQOL-BREF) scores between these two experimental groups. Furthermore, we assessed the incidence of ASD after treatment between these two groups. There were no significant differences in gender, age, body mass index, education, income, type of expense, trauma type, marital status, fracture site, diabetes status, hypertension status, and the pain visual analog scale (VAS) score, activities of daily living (i.e., modified Barthel index) score, and Social Support Rating Scale score between the two experimental groups (p > 0.05). Moreover, no significant differences were found in the prevalence of ASDS before treatment between these two groups (p > 0.05). However, after treatment, the ASDS score was significantly lower in the combined group than in the conventional group (p < 0.05). Furthermore, post-management analysis revealed that the incidence rate of ASD was 24.19% in the conventional group and 8.22% in the combined group. Moreover, the incidence of ASD was significantly lower in the combined group compared to the conventional group (p < 0.05). Before intervention, the difference in the SAS or SDS between patients was not statistically significant (p > 0.05). However, following treatment, the SAS and SDS scores of patients were significantly lower in the combined group than in the conventional group (p < 0.05). Similarly, after treatment, the SRSS scores of patients were substantially lower in the combined group than in the conventional group (p < 0.05). Furthermore, the WHOQOL-BREF score of patients was significantly greater in the combined group than in the conventional group (p < 0.05). MBSR therapy can significantly alleviate ASD in trauma and fracture patients. Furthermore, this approach can alleviate the incidence of ASD and reduce anxiety, depression, and negative emotions in patients. These positive effects collectively improve sleep quality and overall well-being of patients.

Spatial transcriptomics in bone mechanomics: Exploring the mechanoregulation of fracture healing in the era of spatial omics.

In recent decades, the field of bone mechanobiology has sought experimental techniques to unravel the molecular mechanisms governing the phenomenon of mechanically regulated fracture healing. Each cell within a fracture site resides within different local microenvironments characterized by different levels of mechanical strain; thus, preserving the spatial location of each cell is critical in relating cellular responses to mechanical stimuli. Our spatial transcriptomics-based "mechanomics" platform facilitates spatially resolved analysis of the molecular profiles of cells with respect to their local in vivo mechanical environment by integrating time-lapsed in vivo micro-computed tomography, spatial transcriptomics, and micro-finite element analysis. We investigate the transcriptomic responses of cells as a function of the local strain magnitude by identifying the differential expression of genes in regions of high and low strain within a fracture site. Our platform thus has the potential to address fundamental open questions within the field and to discover mechano-responsive targets to enhance fracture healing.

PREDICTOR OF DIPLOPIA IN PURE ORBITAL BLOWOUT FRACTURE: A 14-YEAR RETROSPECTIVE ANALYSIS

PREDICTOR OF DIPLOPIA IN PURE ORBITAL BLOWOUT FRACTURE: A 14-YEAR RETROSPECTIVE ANALYSIS

Effect of hand-wrist exercises on distal radius fracture healing based on markerless motion capture system.

With the internal volar locking plate (VLP) technique emerging as a preferred surgical approach, early post-surgery therapeutic exercises have shown promise in promoting wrist functionality after distal radial fractures (DRFs). The biomechanical microenvironment, particularly the role of biomechanical stimuli, plays a crucial role in guiding stem tissue formation at the fracture site. However, much less is known about how various hand exercises interact with the microenvironment and influence fracture healing outcomes. This study employed the Leap Motion Controller for markerless hand motion capture and utilised an enhanced OpenSim hand model to simulate these motions. An advanced DRF healing model, integrating angiogenesis and the mechano-regulated maturation of callus tissue, was applied to simulate the MSCs differentiation and predict the healing outcomes. The effects of various rehabilitation exercises on DRFs' healing outcomes were systematically analysed. The results showed rehabilitation exercises, such as wrist extension/flexion and ulnar deviation, generally had a higher contact force on the distal radius compared with the slack state. Also, the relationship between contact force and muscle activations was not always linear, reflecting the intricate dynamics of the kinematic system. Exercise could induce changes in the bony bridge and cartilage formation, while angiogenesis remained unaffected. In the initial weeks, gripping exercises proved most beneficial, but as time progressed, extension and flexion exercises became more advantageous. The study highlights the importance of tailoring rehabilitation exercises to the dynamic healing process of DRFs. As the healing trajectory progresses, the therapeutic efficacy of specific exercises evolves, necessitating adaptive and patient-specific rehabilitation programs.

A case and review of FGF23-mediated hypophosphatemic osteomalacia in the absence of pathogenic PHEX variants

Abstract We report an atypical case of fibroblast growth factor-23 (FGF23)-mediated hypophosphatemic osteomalacia without a pathogenic variant (PV) of PHEX, who improved biochemically, clinically and radiologically post burosumab treatment. We present a narrative review of FGF23-mediated hypophosphatemic osteomalacia and propose a roadmap for investigating the etiology of hypophosphatemia to guide therapy. A 29-year-old female with FGF23-mediated hypophosphatemic osteomalacia experienced multiple insufficiency fractures, including bilateral femoral diaphyseal fractures and delayed healing. This occurred on a background of juvenile enthesitis-related arthritis, narcolepsy and brittle dentition since her early teens. Whole-body magnetic resonance imaging and Gallium-68 DOTATATE positron emission tomography scans were unremarkable, making tumor-induced osteomalacia highly unlikely. No hypophosphatemic PVs were found using massively parallel sequencing. Despite phosphate and calcitriol therapy, mild hypophosphatemia persisted with minimal improvement in fracture healing or pain. One dose of 60 mg burosumab, an anti-FGF23 antibody, led to hyperphosphatemia requiring dose titration and three doses of burosumab normalized renal tubular maximum reabsorption rate of phosphate relative to glomerular filtration rate. Burosumab led to fracture healing with callus formation corresponding with improved pain at fracture sites. Hypophosphatemic osteomalacia manifests with varus deformity of the lower limbs, gait disturbance, muscle weakness, enthesopathy, and dental necrosis. Evaluation of the etiology is crucial and requires an algorithmic approach to determine whether hypophosphatemia is renally-mediated, FGF23-mediated, acquired or inherited. The most common inherited cause of FGF23-mediated hypophosphatemic osteomalacia is X-linked hypophosphatemia (XLH) secondary to a PV of the PHEX gene. However, the absence of a PHEX PVs does not exclude a diagnosis of hereditary FGF23-mediated hypophosphatemic osteomalacia. Other inherited causes of this disorder include autosomal dominant and autosomal recessive hypophosphatemic rickets, fibrous dysplasia-McCune-Albright syndrome, cutaneous skeletal hypophosphatemia syndrome and osteoglophonic dysplasia. Burosumab significantly improves serum phosphate and fracture healing in XLH and may effectively treat other forms of FGF23-mediated hypophosphatemia.

Development and Validation of a Preclinical Canine Model for Delayed Onset Fracture-Related Infections

Background: Fracture-Related Infections (FRIs) are a challenging complication in orthopaedics. FRI incidence is considerably high, particularly in open fractures. FRI management typically involves multiple surgical interventions and prolonged antibiotic therapies. This regimen is often ineffective at infection eradication, resulting in poor outcomes and inefficient use of healthcare resources such that improved preventative and therapeutic interventions are needed. To effectively address these gaps, valid preclinical animal models for FRIs are needed. The purpose of this study was to develop and validate a canine ulna model for delayed FRIs that accurately mimics the clinical course noted in patients. Methods: In this model, a distal ulnar ostectomy was established, then internally stabilized with plates and screws that were pre-incubated with methicillin-resistant Staphylococcus aureus. After a 3-week period, all animals underwent irrigation and debridement of the fracture site followed by clinical, radiographic, bacteriologic, and histologic assessments over the subsequent 8 weeks. Results: This preclinical canine model established a valid representation of delayed FRI in patients based on clinical, radiographic, bacteriologic, and histologic features. Bilateral distal ulnar ostectomies stabilized with MRSA-incubated implants were consistently associated with clinical signs of local infection, radiographic evidence for delayed union with osteomyelitis and implant failure, and implant-associated biofilm formation 3 weeks after “fracture” creation. Conclusion: The translational rigor of the model allows for efficient and effective testing of novel preventive and therapeutic interventions aimed at improving outcomes for FRI patients.

Musculoskeletal model predicted paraspinal loading may quick estimate the effect of exercise on spine BMD

PurposeSpine is the most commonly found fracture site due to osteoporosis. Combined exercise including high-impact and resistance exercise shows the potential to improve bone mineral density (BMD) in the spine. However, the mechanical loading introduced by exercise, which is the mechanism of BMD changes, has not been investigated. The purpose of this study is to provide a new insight to investigate the mechanical stimuli of exercise induced bone remodelling.MethodsTen postmenopausal women with osteopenia who finalized a 6-month combined exercise of high-impact and resistance intervention were included. The changes in BMD were analyzed based on QCT images obtained from pre and post intervention. A modified full-body musculoskeletal model was built to estimate paravertebral muscle force (MF) and intervertebral compression force (ICF) during daily activities (walking and heel drop) and combined exercise including high-impact (jumping) and resistance exercise (pulling elastic bands).ResultsThe paravertebral MF and ICF during jumping and pulling elastic bands exercise were all significantly greater than walking and heel drop exercise with up to 1.22–8.18 times. Spine BMD remained at the same level with no significant decline observed, especially at L1 (pre 247.95 ± 26.77 mg/cm3 and post 245.49 ± 22.04 mg/cm3). Comparing with daily activities, significant correlations were observed between the changes of BMD and the sum of spinal loadings generated by combined exercise at both global and segmental level (r = 0.687, p &amp;lt; 0.05).ConclusionIt has been proved that paravertebral muscle forces and intervertebral compression forces generated by the combined exercise, rather than daily exercise, were the main reasons for the improvement of spine BMD. This study contributes into the understanding of exercise induced spine adaptation as well as a potential in fast prediction to evaluate the effect of physical exercise therapy.

Pediatric supracondylar humerus fracture with fascicular median nerve injury: The role of neuromuscular ultrasound in diagnosis and management – a case report

Background Supracondylar humerus fractures are the most common type of elbow fractures in children. Nerve injuries, primarily neuropraxia, are frequent complications and are often managed with a “wait-and-see” approach. Electroneuromyography (ENMG) is the standard method for evaluating peripheral nerve injuries, while ultrasound (US) is valuable for localizing lesions. Objective This case report aims to highlight the beneficial role of US in the follow-up and rehabilitation of nerve injuries following pediatric supracondylar humerus fractures. Case presentation A 4-year-old boy presented with a supracondylar humerus fracture that was treated with closed reduction and K-wire fixation. He exhibited weakness in the first two fingers of his left hand, difficulty grasping, and nail changes. Ultrasound revealed a median nerve lesion adjacent to the fracture site. ENMG indicated an acute severe axonal injury involving the branch innervating the flexor carpi radialis muscle. Following rehabilitation, there was improvement in hand grip strength, measured using a JAMAR hand dynamometer, and in health-related quality of life (QoL), assessed by the Pediatric Outcomes Data Collection Instrument (PODCI) score. Follow-up ENMG showed signs of mild reinnervation. Conclusion Pre-ENMG ultrasound provides crucial information regarding which nerve should be examined with a nerve conduction study and identifies the initial muscle to be evaluated during needle EMG. This aids in accurately localizing nerve damage and guiding effective treatment.

FEA-based Virtual Operation and Stress Distribution Analysis of DHS Screws in Proximal Femoral Bone Fractures: A Strategic Guide for Orthopedic Surgeons in Operational Planning

Background Accidents are the major reasons causing hip bone fractures. These are due to reduced bone density due to aging effect which may cause fractures typically in proximal part of the femur bone. Purpose The purpose of this work is to concentrate on preoperative planning by using a 3D model developed with a virtual operation using a dynamic hip screw (DHS). Methods DHS is generally preferred for the stabilization of stable fractures. The virtual operation was performed on the proximal femoral fracture site, typically for stable fractures. Finite element analysis (FEA) of operated bone was performed to estimate Von Misses stress distribution on the implant post-operatively, resulting in less stress on the fracture site. Results FEA indicates a transfer of stress of the fracture site (35–62%) on the implant, resulting in the operation’s success. Such work will assist orthopedic surgeons in determining load-bearing capacities after the mobilization of the patient. Conclusion Virtual surgery helps the surgeon to identify fracture geometry, the success of the operation, and proper fixation of the implant to avoid post-surgery complications. This aids in the quick recovery of patients, resulting in early rehabilitation.

Bacteriophage Therapy for Acute Fracture-Related Infections: An Effective Treatment When Compared to Antibiotics In A Canine Model.

Acute fracture-related infections are challenging problems, affecting up to 20% of orthopaedic trauma patients. High recurrence rates, secondary surgeries, and rehospitalizations lead to increased healthcare costs and are major burdens to patients. Bacteriophage therapy offers a potential alternative treatment option to address these challenges. In previous studies, it has been shown to be effective against biofilm and bacterial clearance on orthopaedic implants, however, their effects on fracture healing are poorly understood. The aim of this study was to determine if bacteriophages are as good as antibiotic therapy for the treatment of fracture related infection. A canine model was used for this preclinical study examining bacteriophages specifically cultivated against S. aureus (OJ1). Based on sample size calculations and ethical care and use of animals, bilateral 1 cm ulnar defects (n=32; 16 dogs) were created and stabilized using plate and screw fixation. Implants were incubated in a suspension of biofilm-producing Staphylococcus aureus (OJ1). After 3 weeks, bone samples from fracture sites were cultured and surgical sites underwent irrigation and debridement (I&D) with retention of hardware, followed by 1 of 4 treatments (n=8/group): no additional treatment, 6 weeks of parenteral antibiotics, 7 days of bacteriophage therapy, or combination antibiotic/bacteriophage therapy. At 11 weeks, dogs were humanely euthanatized and bacterial load, callus formation, and histomorphometry for callus maturity and biofilm formation were assessed using quantitative microbial bone cultures, radiography and semi-quantitative histomorphometry. At 3 weeks, all surgical sites/ulnae had confirmed infections . At 11 weeks, fractures that received bacteriophage therapy (542 ± 204 CFU/g) had statistically significantly less CFU/g when compared to those (45,065 ± 4,409 CFU/g) that did not receive bacteriophage (p=0.033). Fractures treated with bacteriophages had statistically significantly (p<0.0001) more robust callus formation on radiographs at 11 weeks (77.7% ± 9% vs 52.5% ± 14%), as well as decreased biofilm formation (median = 1 vs 2; p=0.049) and statistically significant (p=0.035) increase in bone formation on histology/histomorphometry when compared to fractures that did not receive bacteriophages (20.7 ± 6 vs 15.7 ± 7). Seven days of bacteriophage therapy was at least as good as 6 weeks of antibiotic therapy in terms of clearance of acute fracture-related infections. It was superior in terms of reduction in CFU/g, better callus formation, and biofilm clearance.

Fixation of Takeuchi Type II/III lateral hinge fractures provides favourable stability of a medial open wedge high tibial osteotomy-A biomechanical study.

To investigate the biomechanical consequences of osteosynthesis of lateral hinge fractures (LHFs) in medial open wedge high tibial osteotomy (MOWHTO). Sixteen fresh-frozen human cadaveric proximal tibiae underwent MOWHTO fixed with an ipsilateral locking compression plate. The specimens were assigned to two clusters simulating LHFs according to the Takeuchi classification: (1) Type II fracture; and (2) Type III fracture. The following conditions were serially tested: (1) intact hinge; (2) fractured hinge; (3) screw fixation of the LHF; (4) staple fixation of the LHF; and (5) locking T-plate fixation of the LHF. Each specimen was subjected to 10 cycles of axial compression load (720 N; 36 N/s), and internal and external rotational loads (10 N m; 1 N m/s), while capturing the interfragmentary movements via motion tracking. In Takeuchi Type II fractures, osteosynthesis of the fractured hinge with staples or a plate significantly reduced fracture site displacement (p < 0.05) and significantly increased construct stiffness (p < 0.05) under axial and torsional loading, while only the plate restored intact torsional displacement (n.s.). For Takeuchi Type III fractures, both screw and plate fixation significantly reduced fracture site displacement (p < 0.05) and significantly increased construct stiffness (p < 0.05) under axial and torsional loading. Both techniques restored torsional stiffness in each rotational direction and torsional displacement in internal rotation (n.s.). Additional plate fixation of Takeuchi Type II fractures was the construct with the highest stiffness, restoring the axial and torsional stability to a MOWHTO with an intact hinge. Screw and plate fixation of Takeuchi Type III fractures provided equivalent stability and restored the torsional and axial stability of the MOWHTO. In case of a Takeuchi Type II or III fracture, surgeons should consider additional plate or screw osteosynthesis of the fractured hinge to best restore the stability of the MOWHTO, which may potentially reduce the risk of loss of correction and impaired bone healing. There is no level of evidence as this study was an experimental laboratory study.

Frequency of Osteoporosis-Related Fractures in the Kingdom of Bahrain.

Osteoporosis-related fragility fractures are increasing worldwide. An assessment of the prevalence of fragility fractures in Bahrain is needed to determine proper action and preventive strategies. The main objective of this study was to conduct a retrospective cross-sectional study to investigate the prevalence of fragility fractures in adult Bahraini patients. Another objective was to explore the relationship of fragility fracture risk with BMD, age, sex, BMI, vitamin D status, and therapy. To investigate the fragility fractures, we retrospectively reviewed the dual-energy X-ray absorptiometry (DEXA) data of patients who underwent scans for the diagnosis of osteoporosis between 2016 and 2018. The data were collected from four large centers in Bahrain. The patients' medical records were reviewed for the fragility fracture data, BMD, sex, age, BMI, vitamin D status, and therapy. Among a total of 4572 patients who visited the radiology departments during the 3-year study period, only 412 patients with fragility fractures were considered for the current study. The mean age of the patients in this cohort was 63.9 ± 12.2 years. There were 393 females (95.6%). Among the 431 fragility fractures, there were 175 (40.6%) belonging to three common fracture sites: vertebral (86, 20.9%), femur (60, 14.6%), and distal radius (Colles) fractures (29, 7%). Other fragility fractures were hand (7%), radius and ulna (3.7%), humerus (6.5%), tibia and fibula (5.6%), foot/ankle (27.9%), ribs (3.0%), and pelvis (1.6%). Our results revealed a significant association between the fragility fractures and BMD (χ2 = 6.7, p = 0.035). We reported a significant association of fragility fracture with sex (p = 0.006) and with denosumab therapy (p < 0.001). This study reported a reduced BMD and an increased prevalence of fragility fractures among Bahraini subjects. The highest frequencies of fragility fractures among our cohort were foot/ankle, vertebral, and hip fractures, respectively. We showed a statistically significant association between fragility fractures and BMD. The current study indicated that not only patients with low BMD but also patients with fragility fractures were undertreated. Thus, the immediate initiation of treatment and the synthesis of local osteoporosis treatment guidelines are warranted.

Biofidelity Assessment of the GHBMC M50-O Seated in a Honda Accord Seat in a Rear-Facing Configuration during a High-Speed Frontal Impact

&lt;div&gt;Vehicles equipped with automated driving systems (ADS) may have non-traditional seating configurations, such as rear-facing for front-row occupants. The objectives of this study are (1) to generate biomechanical corridors from kinematic data obtained from postmortem human subjects (PMHS) sled tests and (2) to assess the biofidelity of the Global Human Body Models Consortium (GHBMC) 50th male (M50-O) v6.0 seated in an upright (25-deg recline) Honda Accord seat with a fixed D-ring (FDR) in a 56 km/h rear-facing frontal impact. A phase optimization technique was applied to mass-normalized PMHS data for generating corridors. After replicating the experimental boundary conditions in the computational finite element (FE) environment, the performance of the rigidized FE seat model obtained was validated using LSTC Hybrid III FE model simulations and comparison with experiments. The most recent National Highway Traffic Safety Administration (NHTSA) Biofidelity Ranking System (BRS) method was used to assess the biofidelity of the GHBMC M50-O. The occupant response score for GHBMC was 2.00. The average normalized root mean squared deviation (NRMSD) for seat reaction loads in the GHBMC simulation was less than 10%. Peak T-spine accelerations (avg. BRS = 2.28) and anterior-to-posterior (AP) chest deflection (BRS = 2.61) were underestimated. No rib fractures were predicted in the GHBMC using the default failure strain criteria of 1.8%; however, fractures were predicted in the 3rd rib (both left and right sides) using an updated failure strain criteria of 0.52%. Ramping up the seat back, as indicated by pelvis Z-displacement, was underestimated using a coefficient of contact friction of 0.2 (BRS = 3.65) but improved using a coefficient of 0.1 (BRS = 1.44). Local strain hotspots were predicted at the pubic rami locations in the GHBMC, corresponding well with fracture sites in the PMHS.&lt;/div&gt;

Animal Models for Fracture-Related Infections: A Systematic Review

Background: Fracture-Related Infections (FRIs) are among the most challenging complications in orthopaedics. The incidence of these infections is high, particularly in complex, open fractures. FRI management typically involves irrigation and debridement of the fracture site, implant exchange and prolonged antibiotic therapy. This regimen is often ineffective resulting in poor patient outcomes and inefficient use of healthcare resources. As such, improved diagnostic, preventative and therapeutic interventions are needed. To effectively address these gaps, valid preclinical animal models that accurately replicate clinical FRIs are required. The purpose of this systematic review was to synthesize the relevant peer-reviewed literature related to FRI animal models to analyze their translational rigor and potential. Methods: An online database search was conducted using PubMed in which 77 articles were eligible for inclusion in this review. Results: Data extraction revealed a wide spectrum of animal species, methods for bone defect creation and fixation, bacterial inoculum deliveries and doses and intervention time points among the studies. Further, clinical, radiographic, microbiologic and histologic outcomes of infected control groups were assessed to determine validity of each model. Importantly, FRI-defining features such as bacterial biofilms and delayed fracture union were only reported in 20.8% and 29.9% of models, respectively. Conclusion: While it is challenging to incorporate and validate all clinically relevant components of FRIs into an animal model, many of the gaps identified in this systematic review can and should be addressed to improve the efficacy of preclinical evidence aimed at advancing FRI management. Keywords: Complex Open Fractures; Fracture-Related Infections; Fracture Management; Pre-Clinical Models; Animal Models

Comparison of chromosomal microarray and karyotyping in prenatal diagnosis using 491 amniotic fluid samples.

This study was aimed to investigate the performance of chromosomal microarray analysis (CMA) in prenatal diagnosis compared with traditional karyotyping analysis. Both CMA and karyotyping analyses were performed to detect the karyotypes in the amniotic fluid of 491 pregnant women who got prenatal diagnosis at the Center of Prenatal Diagnosis of Shangrao (China) during January 2019 to April 2021. After excluding 2 samples in the CMA analysis and 2 samples in the karyotyping analysis which were failed in detection, the remaining 487 amniotic fluid samples were detected. Both CMA and karyotyping analyses identified 22 cases of aneuploidy chromosome abnormalities, including trisomy 21 (10 cases), trisomy 18 (4 cases), sex chromosome abnormality (5 cases), and other chromosome abnormalities (3 cases). In addition, CMA and karyotyping analyses found 8 cases of fetal chromosomal imbalance. Interestingly, abnormal results were detected by CMA analysis in 10 cases whose results were normal by karyotype analysis. Furthermore, 23 cases of copy number variation (CNVs) with variation of unknown clinical significance (VOUS) were detected by CMA, which accounted for 4.68% (23/491) in all cases. However, CMA was not able to accurately identify some complex karyotypes and mixed chimeras, including 2 cases of chimeras, 4 cases of balanced translocations, 4 cases of pericentric inversions, and 8 cases of other chromosome polymorphisms, indicating karyotyping analysis was superior to detect these chromosome abnormalities compared with CMA analysis. CMA was better in detecting the fracture sites, microduplication and microdeletion with definite pathogenicity, and CNVs with VOUS compared with karyotype analysis.

Single-nucleus transcriptomics reveal the differentiation trajectories of periosteal skeletal/stem progenitor cells in bone regeneration.

Bone regeneration is mediated by skeletal stem/progenitor cells (SSPCs) that are mainly recruited from the periosteum after bone injury. The composition of the periosteum and the steps of SSPC activation and differentiation remain poorly understood. Here, we generated a single-nucleus atlas of the periosteum at steady state and of the fracture site during the early stages of bone repair (https://fracture-repair-atlas.cells.ucsc.edu). We identified periosteal SSPCs expressing stemness markers (Pi16 and Ly6a/SCA1) and responding to fracture by adopting an injury-induced fibrogenic cell (IIFC) fate, prior to undergoing osteogenesis or chondrogenesis. We identified distinct gene cores associated with IIFCs and their engagement into osteogenesis and chondrogenesis involving Notch, Wnt, and the circadian clock signaling, respectively. Finally, we show that IIFCs are the main source of paracrine signals in the fracture environment, suggesting a crucial paracrine role of this transient IIFC population during fracture healing. Overall, our study provides a complete temporal topography of the early stages of fracture healing and the dynamic response of periosteal SSPCs to injury, redefining our knowledge of bone regeneration.

Single-nucleus transcriptomics reveal the differentiation trajectories of periosteal skeletal/stem progenitor cells in bone regeneration

Bone regeneration is mediated by skeletal stem/progenitor cells (SSPCs) that are mainly recruited from the periosteum after bone injury. The composition of the periosteum and the steps of SSPC activation and differentiation remain poorly understood. Here, we generated a single-nucleus atlas of the periosteum at steady state and of the fracture site during the early stages of bone repair (https://fracture-repair-atlas.cells.ucsc.edu). We identified periosteal SSPCs expressing stemness markers (Pi16 and Ly6a/SCA1) and responding to fracture by adopting an injury-induced fibrogenic cell (IIFC) fate, prior to undergoing osteogenesis or chondrogenesis. We identified distinct gene cores associated with IIFCs and their engagement into osteogenesis and chondrogenesis involving Notch, Wnt, and the circadian clock signaling, respectively. Finally, we show that IIFCs are the main source of paracrine signals in the fracture environment, suggesting a crucial paracrine role of this transient IIFC population during fracture healing. Overall, our study provides a complete temporal topography of the early stages of fracture healing and the dynamic response of periosteal SSPCs to injury, redefining our knowledge of bone regeneration.