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Scientific Reports Jun 2024Our main objective was to use machine learning methods to identify significant structural factors associated with pain severity in knee osteoarthritis patients....
Our main objective was to use machine learning methods to identify significant structural factors associated with pain severity in knee osteoarthritis patients. Additionally, we assessed the potential of various classes of imaging data using machine learning techniques to gauge knee pain severity. The data of semi-quantitative assessments of knee radiographs, semi-quantitative assessments of knee magnetic resonance imaging (MRI), and MRI images from 567 individuals in the Osteoarthritis Initiative (OAI) were utilized to train a series of machine learning models. Models were constructed using five machine learning methods: random forests (RF), support vector machines (SVM), logistic regression (LR), decision tree (DT), and Bayesian (Bayes). Employing tenfold cross-validation, we selected the best-performing models based on the area under the curve (AUC). The study results indicate no significant difference in performance among models using different imaging data. Subsequently, we employed a convolutional neural network (CNN) to extract features from magnetic resonance imaging (MRI), and class activation mapping (CAM) was utilized to generate saliency maps, highlighting regions associated with knee pain severity. A radiologist reviewed the images, identifying specific lesions colocalized with the CAM. The review of 421 knees revealed that effusion/synovitis (30.9%) and cartilage loss (30.6%) were the most frequent abnormalities associated with pain severity. Our study suggests cartilage loss and synovitis/effusion lesions as significant structural factors affecting pain severity in patients with knee osteoarthritis. Furthermore, our study highlights the potential of machine learning for assessing knee pain severity using radiographs.
Topics: Humans; Osteoarthritis, Knee; Machine Learning; Magnetic Resonance Imaging; Female; Male; Middle Aged; Aged; Knee Joint; Severity of Illness Index; Pain; Support Vector Machine; Bayes Theorem
PubMed: 38926487
DOI: 10.1038/s41598-024-65613-0 -
BMJ Open Jun 2024
PubMed: 38925708
DOI: 10.1136/bmjopen-2023-080301corr1 -
BMJ Open Jun 2024To assess compliance with statutory requirements to register and report outcomes in interventional trials of mesenchymal stromal cells (MSCs) for musculoskeletal...
OBJECTIVE
To assess compliance with statutory requirements to register and report outcomes in interventional trials of mesenchymal stromal cells (MSCs) for musculoskeletal disorders and to describe the trials' clinical and design characteristics.
DESIGN
A systematic review of published trials and trials submitted to public registries.
DATA SOURCES
The databases Medline, Cochrane Library and McMaster; six public clinical registries. All searches were done until 31 January 2023.
ELIGIBILITY CRITERIA
Trials submitted to registries and completed before January 2021. Prospective interventional trials published in peer-reviewed journals.
DATA EXTRACTION AND SYNTHESIS
The first author searched for trials that had (1) posted trial results in a public registry, (2) presented results in a peer-reviewed publication and (3) submitted a pretrial protocol to a registry before publication. Other extracted variables included trial design, number of participants, funding source, follow-up duration and cell type.
RESULTS
In total 124 trials were found in registries and literature databases. Knee osteoarthritis was the most common indication. Of the 100 registry trials, 52 trials with in total 2 993 participants had neither posted results in the registry nor published results. Fifty-two of the registry trials submitted a protocol retrospectively. Forty-three of the 67 published trials (64%) had registered a pretrial protocol. Funding source was not associated with compliance with reporting requirements. A discrepancy between primary endpoints in the registry and publication was found in 16 of 25 trials. In 28% of trials, the treatment groups used adjuvant therapies. Only 39% of controlled trials were double-blinded.
CONCLUSIONS
A large proportion of trials failed to comply with statutory requirements for the registration and reporting of results, thereby increasing the risk of bias in outcome assessments. To improve confidence in the role of MSCs for musculoskeletal disorders, registries and medical journals should more rigorously enforce existing requirements for registration and reporting.
Topics: Humans; Registries; Musculoskeletal Diseases; Mesenchymal Stem Cell Transplantation; Clinical Trials as Topic; Guideline Adherence; Research Design; Mesenchymal Stem Cells
PubMed: 38925685
DOI: 10.1136/bmjopen-2023-081343 -
Osteoarthritis and Cartilage Jun 2024Mammalian somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) via the forced expression of Yamanaka reprogramming factors. However, only a...
OBJECTIVE
Mammalian somatic cells can be reprogrammed into induced pluripotent stem cells (iPSCs) via the forced expression of Yamanaka reprogramming factors. However, only a limited population of the cells that pass through a particular pathway can metamorphose into iPSCs, while the others do not. This study aimed to clarify the pathways that chondrocytes follow during the reprogramming process.
DESIGN
The fate of human articular chondrocytes under reprogramming was investigated through a time-coursed single-cell transcriptomic analysis, which we termed an inverse genetic approach. The iPS interference technique was also employed to verify that chondrocytes inversely return to pluripotency following the proper differentiation pathway.
RESULTS
We confirmed that human chondrocytes could be converted into cells with an iPSC phenotype. Moreover, it was clarified that a limited population that underwent the silencing of SOX9, a master gene for chondrogenesis, at a specific point during the proper transcriptome transition pathway, could eventually become iPSCs. Interestingly, the other cells, which failed to be reprogrammed, followed a distinct pathway toward cells with a surface zone chondrocyte phenotype. The critical involvement of cellular communication network factors (CCNs) in this process was indicated. The idea that chondrocytes, when reprogrammed into iPSCs, follow the differentiation pathway backward was supported by the successful iPS interference using SOX9.
CONCLUSIONS
This inverse genetic strategy may be useful for seeking candidates for the master genes for the differentiation of various somatic cells. The utility of CCNs in articular cartilage regeneration is also supported.
PubMed: 38925474
DOI: 10.1016/j.joca.2024.06.009 -
Pharmacological Research Jun 2024Ephrin-B-EphB signaling can promote pain through ligand-receptor interactions between peripheral cells, like immune cells expressing ephrin-Bs, and EphB receptors...
Ephrin-B-EphB signaling can promote pain through ligand-receptor interactions between peripheral cells, like immune cells expressing ephrin-Bs, and EphB receptors expressed by DRG neurons. Previous studies have shown increased ephrin-B2 expression in peripheral tissues like synovium of rheumatoid and osteoarthritis patients, indicating the clinical significance of this signaling. The primary goal of this study was to understand how ephrin-B2 acts on mouse and human DRG neurons, which express EphB receptors, to promote pain and nociceptor plasticity. We hypothesized that ephrin-B2 would promote nociceptor plasticity and hyperalgesic priming through MNK-eIF4E signaling, a critical mechanism for nociceptive plasticity induced by growth factors, cytokines and nerve injury. Both male and female mice developed dose-dependent mechanical hypersensitivity in response to ephrin-B2, and both sexes showed hyperalgesic priming when challenged with PGE injection either to the paw or the cranial dura. Acute nociceptive behaviors and hyperalgesic priming were blocked in mice lacking MNK1 (Mknk1 knockout mice) and by eFT508, a specific MNK inhibitor. Sensory neuron-specific knockout of EphB2 using Pirt-Cre demonstrated that ephrin-B2 actions require this receptor. In Ca-imaging experiments on cultured DRG neurons, ephrin-B2 treatment enhanced Ca transients in response to PGE and these effects were absent in DRG neurons from MNK1 and EphB2-Pirt mice. In experiments on human DRG neurons, ephrin-B2 increased eIF4E phosphorylation and enhanced Ca responses to PGE treatment, both blocked by eFT508. We conclude that ephrin-B2 acts directly on mouse and human sensory neurons to induce nociceptor plasticity via MNK-eIF4E signaling, offering new insight into how ephrin-B signaling promotes pain.
PubMed: 38925462
DOI: 10.1016/j.phrs.2024.107284 -
Journal of Cachexia, Sarcopenia and... Jun 2024Preclinical rheumatoid arthritis (Pre-RA) is defined as the early stage before the development of clinical RA. While cachexia is a well-known and potentially modifiable...
BACKGROUND
Preclinical rheumatoid arthritis (Pre-RA) is defined as the early stage before the development of clinical RA. While cachexia is a well-known and potentially modifiable complication of RA, it is not known if such an association exists also in the Pre-RA stage. To investigate such issue, we aimed to compare the longitudinal alterations in the muscle composition and adiposity of participants with Pre-RA with the matched controls.
METHODS
In this observational cohort study, the Osteoarthritis Initiative (OAI) participants were categorized into Pre-RA and propensity score (PS)-matched control groups. Pre-RA was retrospectively defined as the absence of RA from baseline to year-2, with progression to physician-diagnosed clinical RA between years 3-8 of the follow-up period. Using a validated deep learning algorithm, we measured MRI biomarkers of thigh muscles and adiposity at baseline and year-2 follow-ups of the cohort. The outcomes were the differences between Pre-RA and control groups in the 2-year rate of change for thigh muscle composition [cross-sectional area (CSA) and intramuscular adipose tissue (Intra-MAT)] and adiposity [intermuscular adipose tissue (Inter-MAT) and subcutaneous adipose tissue (SAT)]. Linear mixed-effect regression models were used for comparison.
RESULTS
After 1:3 PS-matching of the groups for confounding variables (demographics, risk factors, co-morbidities, and knee osteoarthritis status), 408 thighs (102 Pre-RA and 306 control) of 322 participants were included (age mean ± SD: 61.7 ± 8.9 years; female/male: 1.8). Over a 2-year period, Pre-RA was associated with a larger decrease in total thigh muscle CSA [estimate, 95% confidence interval (CI): -180.13 mm/2-year, -252.80 to -107.47, P-value < 0.001]. Further examination of thigh muscle composition showed that the association of the presence of Pre-RA with a larger decrease in muscle CSA over 2 years was noticeable in the quadriceps, flexors, and sartorius muscle groups (P-values < 0.05). Comparison of changes in total adipose tissue showed no difference between Pre-RA and control participants (estimate, 95% CI: 48.48 mm/2-year, -213.51 to 310.47, P-value = 0.691). However, in the detailed analysis of thigh adiposity, Pre-RA presence was associated with a larger increase in Inter-MAT (estimate, 95% CI: 150.55 mm/2-year, 95.58 to 205.51, P-value < 0.001).
CONCLUSIONS
Preclinical rheumatoid arthritis is associated with a decrease in muscle cross-sectional area and an increase in intermuscular adipose tissue, similar to rheumatoid cachexia in clinical rheumatoid arthritis. These findings suggest the presence of cachexia in the preclinical phase of rheumatoid arthritis. Given that cachexia, which can exacerbate health outcomes, is potentially modifiable, this study emphasizes the importance of early identification of patients in their preclinical phase.
PubMed: 38923846
DOI: 10.1002/jcsm.13533 -
Orthopaedic Surgery Jun 2024The distal femur is one of the most common sites for primary bone tumors. As the tumor progresses and bone destruction worsens, it can severely affect knee function and... (Review)
Review
The distal femur is one of the most common sites for primary bone tumors. As the tumor progresses and bone destruction worsens, it can severely affect knee function and even pose a threat to life. In cases where only one condyle is affected and requires resection, preserving the healthy contralateral condyle can substantially enhance the biomechanics of the knee. Furthermore, preserving bone stock may enable future salvage procedures in the event of initial surgery failure, be it from fractures or osteoarthritis. Distal femoral unicondyle resection can offer better functional outcomes in select cases. However, it is essential to prioritize oncological safety with adequate margins over short-term knee function. Currently, the primary methods for reconstruction after the excision of a unicondylar tumor include allograft transplantation (bi- or uni-condylar) and prosthetic or allograft-prosthesis composite replacement (APC). However, there is currently some controversy regarding the optimal surgical reconstruction method, and a consensus within the academic community has yet to be reached. Moreover, due to the rarity of bone tumors, extensive clinical data from a single center is limited. Current studies are mainly retrospective and single-center, lacking sufficient cases and follow-up duration. This article reviews surgical reconstruction after solitary condylar excision in distal femoral tumors. It summarizes, compares, and analyzes mainstream reconstruction methods, exploring their technical details and clinical outcomes to highlight their potential in bone oncology.
PubMed: 38923385
DOI: 10.1111/os.14119 -
Journal of Patient-reported Outcomes Jun 2024The Good Life with osteoArthritis: Denmark (GLA:D™), an evidence-based education and exercise program designed for conservative management of knee and hip...
BACKGROUND
The Good Life with osteoArthritis: Denmark (GLA:D™), an evidence-based education and exercise program designed for conservative management of knee and hip osteoarthritis (OA), has been shown to benefit participants by reducing pain, improving function, and quality of life. Standardized reporting in the GLA:D databases enabled the measurement of self-reported and performance-based outcomes. There is a paucity of qualitative research on the participants' perceptions of this program, and it is important to understand whether participants' perceptions of the benefits of the program align with reported quantitative findings.
METHODS
We conducted semi-structured telephone interviews with individuals who participated in the GLA:D program from January 2017 to December 2018 in Alberta, Canada. Data were analyzed using an interpretive description approach and thematic analysis to identify emergent themes and sub-themes associated with participants perceived benefits of the GLA:D program. We analyzed the data using NVivo Pro software. Member checking and bracketing were used to ensure the rigour of the analysis.
RESULTS
30 participants were interviewed (70% female, 57% rural, 73% knee OA). Most participants felt the program positively benefited them. Two themes emerged from the analysis: wellness and self-efficacy. Participants felt the program benefited their wellness, particularly with regard to pain relief, and improvements in mobility, strength, and overall well-being. Participants felt the program benefited them by promoting a sense of self-efficacy through improving the confidence to perform exercise and routine activities, as well as awareness, and motivation to manage their OA symptoms. Twenty percent of participants felt no benefits from the program due to experiencing increased pain and feeling their OA was too severe to participate.
DISCUSSION
The GLA:D program was viewed as beneficial to most participants, this study also identified factors (e.g., severe OA, extreme pain) as to why some participants did not experience meaningful improvements. Early intervention with the GLA:D program prior to individuals experiencing severe OA could help increase the number of participants who experience benefits from their participation.
CONCLUSION
As the GLA:D program expands across jurisdictions, providers of the program may consider recruitment earlier in disease progression and targeting those with mild and moderate OA.
Topics: Humans; Female; Osteoarthritis, Knee; Male; Qualitative Research; Osteoarthritis, Hip; Middle Aged; Aged; Quality of Life; Exercise Therapy; Alberta; Interviews as Topic; Self Efficacy; Patient Education as Topic
PubMed: 38922491
DOI: 10.1186/s41687-024-00740-w -
Insights Into Imaging Jun 2024To explore the feasibility of Ultra-short echo time (UTE) - MRI quantitative imaging in detecting early cartilage degeneration in vivo and underlying pathological and...
OBJECTIVES
To explore the feasibility of Ultra-short echo time (UTE) - MRI quantitative imaging in detecting early cartilage degeneration in vivo and underlying pathological and biochemical basis.
METHODS
Twenty volunteers with osteoarthritis (OA) planning for total knee arthroplasty (TKA) were prospectively recruited. UTE-MRI sequences and conventional sequences were performed preoperatively. Regions of interests (ROIs) were manually drawn on the tibial plateau and lateral femoral condyle images to calculate MRI values. Cartilage samples were collected during TKA according to the preset positions corresponding to MR images. Pathological and biochemical components of the corresponding ROI, including histological grading, glycosaminoglycan (GAG) content, collagen integrity, and water content were obtained.
RESULTS
91 ROIs from volunteers of 7 males (age range: 68 to 78 years; 74 ± 3 years) and 13 females (age range: 57 to 79 years; 67 ± 6 years) were evaluated. UTE-MTR (r = -0.619, p < 0.001), UTE-AdiabT1ρ (r = 0.568, p < 0.001), and UTE-T2* values (r = -0.495, p < 0.001) showed higher correlation with Mankin scores than T2 (r = 0.287, p = 0.006) and T1ρ (r = 0.435, p < 0.001) values. Of them, UTE-MTR had the highest diagnostic performance (AUC = 0.824, p < 0.001). UTE-MTR, UTE-AdiabT1ρ and UTE-T2* value was mainly related to collagen structural integrity, PG content and water content, respectively (r = 0.536, -0.652, -0.518, p < 0.001, respectively).
CONCLUSION
UTE-MRI have shown greater in vivo diagnostic value for early cartilage degeneration compared to conventional T2 and T1ρ values. Of them, UTE-MTR has the highest diagnostic efficiency. UTE-MTR, UTE-AdiabT1ρ, and UTE-T2* value mainly reflect different aspects of cartilage degeneration--integrity of collagen structure, PG content, and water content, respectively.
CRITICAL RELEVANCE STATEMENT
Ultra-short echo time (UTE)-MRI has the potential to be a novel image biomarkers for detecting early cartilage degeneration in vivo and was correlated with biochemical changes of early cartilage degeneration.
KEY POINTS
Conventional MR may miss some early cartilage changes due to relatively long echo times. Ultra-short echo time (UTE)-MRI showed the ability in identifying early cartilage degeneration in vivo. UTE-MT, UTE-AdiabT1ρ, and UTE-T2* mapping mainly reflect different aspects of cartilage degeneration.
PubMed: 38922455
DOI: 10.1186/s13244-024-01734-4 -
Critical Care Science 2024Boswellia serrata is an herbal extract from the Boswellia serrata tree that has anti-inflammatory and analgesic properties and alleviates pain caused by rheumatoid...
Boswellia serrata is an herbal extract from the Boswellia serrata tree that has anti-inflammatory and analgesic properties and alleviates pain caused by rheumatoid arthritis, gout, osteoarthritis, and sciatica. Syndrome of inappropriate antidiuretic hormone secretion accompanied by hyponatremia, seizures, and rhabdomyolysis as a manifestation of Boswellia serrata intoxication has not been reported previously. A 38-year-old female suffered clinically isolated syndrome and has since been regularly taking B. serrata capsules (200mg/d) to strengthen her immune system. She experienced hypersensitivity to light, ocular pain, nausea, dizziness, and lower limb weakness four days after receiving her first BNT162b2 vaccine dose, and she increased the dosage of B. serrata to five capsules (1000mg/d) one week after vaccination. After taking B. serrata at a dosage of 1000mg/d for 3 weeks, she was admitted to the intensive care unit because of a first, unprovoked generalized tonic-clonic seizure. The patient's workup revealed syndrome of inappropriate antidiuretic hormone secretion, which resolved completely upon treatment and discontinuation of B. serrata. In summary, B. serrata potentially causes syndrome of inappropriate antidiuretic hormone secretion when it is taken at high doses. Patients should not self-medicate.
Topics: Humans; Female; Adult; Inappropriate ADH Syndrome; Hyponatremia; Rhabdomyolysis; Seizures; Boswellia; Plant Extracts
PubMed: 38922237
DOI: 10.62675/2965-2774.20240049-en