ABSTRACT
OBJECTIVE: We developed a few-shot learning (FSL) framework for the diagnosis of osteopenia and osteoporosis in knee X-ray images. METHODS: Computer vision models containing deep convolutional neural networks were fine-tuned to enable generalization from natural images (ImageNet) to chest X-ray images (normal vs. pneumonia, base images). Then, a series of automated machine learning classifiers based on the Euclidean distances of base images were developed to make predictions for novel images (normal vs. osteopenia vs. osteoporosis). The performance of the FSL framework was compared with that of junior and senior radiologists. In addition, the gradient-weighted class activation mapping algorithm was used for visual interpretation. RESULTS: In Cohort #1, the mean accuracy (0.728) and sensitivity (0.774) of the FSL models were higher than those of the radiologists (0.512 and 0.448). A diagnostic pipeline of FSL model (first)-radiologists (second) achieved better performance (0.653 accuracy, 0.582 sensitivity, and 0.816 specificity) than radiologists alone. In Cohort #2, the diagnostic pipeline also showed improved performance. CONCLUSIONS: The FSL framework yielded practical performance with respect to the diagnosis of osteopenia and osteoporosis in comparison with radiologists. This retrospective study supports the use of promising FSL methods in computer-aided diagnosis tasks involving limited samples.
Subject(s)
Bone Diseases, Metabolic , Osteoporosis , Humans , Osteoporosis/diagnostic imaging , Osteoporosis/diagnosis , Bone Diseases, Metabolic/diagnostic imaging , Bone Diseases, Metabolic/diagnosis , Female , Male , Middle Aged , Aged , Knee/diagnostic imaging , Knee/pathology , Algorithms , Neural Networks, Computer , Machine Learning , Radiography/methods , Adult , Retrospective Studies , Knee Joint/diagnostic imaging , Knee Joint/pathology , Diagnosis, Computer-Assisted/methodsSubject(s)
Abnormalities, Multiple , Genetic Diseases, X-Linked , Knee , Humans , Male , Diagnosis, Differential , Ichthyosiform Erythroderma, Congenital/diagnosis , Ichthyosiform Erythroderma, Congenital/pathology , Keratosis/pathology , Keratosis/diagnosis , Knee/pathology , Limb Deformities, Congenital/diagnosis , AdultABSTRACT
OBJECTIVES: To develop an intensive training programme for ultrasound (US)-guided synovial tissue (ST) biopsy on knees and wrists in inflammatory arthritis and to assess the learning curve, patient tolerability, sample quality and trainees' expectations. METHODS: Active or remission rheumatoid arthritis patients were enrolled. Nine trainees joined the 4-month programme in a centre experienced in performing US-guided ST biopsies consisting of four sequential phases: (1) observation, (2) performance of guided step-by-step phases, (3) execution of the whole procedure on paired joints (knees or wrists) of the same patient in parallel with the trainer and (4) performance of the procedure autonomously. Sample representativity was assessed by histology, and procedure-related adverse events were recorded. Before and after the programme, trainees' expectations and perceptions were collected. RESULTS: 328 ST biopsy procedures were included. The rate of trainees' informative samples was: (1) comparable to the trainers in active and remission knees, but lower in active wrists (70% for trainees vs 100% for trainers, p=0.06) in phase 3; (2) excellent on active knees and wrists (91.9% and 90.9% respectively) but lower (77.6%, p=0.0089) on remission knees in phase 4. Procedures performed by trainees did not affect patient tolerability. Trainees' expectations about procedure-related invasiveness and pain infliction decreased while the difficulty of procedure execution on active wrists and remission knees remained perceived as moderately difficult. CONCLUSIONS: This intensive training programme develops advanced skills in the performance of US-guided ST biopsy on knees and wrists, yielding high-quality specimens available for basic and translational studies on inflammatory joint diseases.
Subject(s)
Education , Image-Guided Biopsy , Ultrasonography, Interventional , Humans , Arthritis, Rheumatoid/diagnostic imaging , Arthritis, Rheumatoid/pathology , Inflammation , Wrist/pathology , Knee/pathologyABSTRACT
OBJECTIVE: The first publication on morphometric analysis of articular cartilage using magnetic resonance imaging (MRI) in 1994 set the scene for a game change in osteoarthritis (OA) research. The current review highlights milestones in cartilage and bone morphometry, summarizing the rapid progress made in imaging, its application to understanding joint (patho-)physiology, and its use in interventional clinical trials. METHODS: Based on a Pubmed search of articles from 1994 to 2023, the authors subjectively selected representative work illustrating important steps in the development or application of magnetic resonance-based cartilage and bone morphometry, with a focus on studies in humans, and on the knee. Research on OA-pathophysiology is addressed only briefly, given length constraints. Compositional and semi-quantitative assessment are not covered here. RESULTS: The selected articles are presented in historical order as well as by content. We review progress in the technical aspects of image acquisition, segmentation and analysis, advances in understanding tissue growth, physiology, function, and adaptation, and a selection of clinical trials examining the efficacy of interventions on knee cartilage and bone. A perspective is provided of how lessons learned may be applied to future research and clinical management. CONCLUSIONS: Over the past 30 years, MRI-based morphometry of cartilage and bone has contributed to a paradigm shift in understanding articular tissue physiology and OA pathophysiology, and to the development of new treatment strategies. It is likely that these technologies will continue to play a key role in the development and (accelerated) approval of therapy, potentially targeted to different OA phenotypes.
Subject(s)
Cartilage, Articular , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/pathology , Knee Joint/diagnostic imaging , Knee Joint/pathology , Magnetic Resonance Imaging/methods , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/pathology , Knee/pathologyABSTRACT
BACKGROUND: Osteoid osteoma (OO) is a benign lesion characterized by an increased fibrous component in the bone marrow, presence of bone-like structures within the medullary cavity, and a surrounding sclerotic bone rim. Reports on OO located in the posterior proximal tibia are rare. CASE SUMMARY: Herein, we report the case of an 18-year-old male, admitted for the evaluation of right knee pain. The right knee pain had started 6 months prior without any apparent cause, which was notably severe at night, affecting sleep, and was exacerbated while climbing stairs or bearing weight. The patient also experienced pain on flexion. Three-dimensional computed tomography and magnetic resonance imaging revealed a nodular lesion beneath the cortical bone of the posterior medial plateau of the right tibia and an abnormal signal focus on the posterior lateral aspect of the right tibial plateau associated with extensive bone marrow edema. A small amount of fluid was present in the right knee joint capsule. The patient subsequently underwent arthroscopic excision of the OO. Postoperatively, there was significant relief of pain, and the knee range of motion returned to normal. CONCLUSION: Although OO in the posterior proximal tibia is a rare occurrence, it can be effectively excised through minimally invasive arthroscopic visualization.
Subject(s)
Bone Neoplasms , Osteoma, Osteoid , Male , Humans , Adolescent , Tibia/diagnostic imaging , Tibia/surgery , Tibia/pathology , Osteoma, Osteoid/diagnostic imaging , Osteoma, Osteoid/surgery , Bone Neoplasms/diagnostic imaging , Bone Neoplasms/surgery , Bone Neoplasms/complications , Pain/complications , Knee/pathologyABSTRACT
Bone marrow edema represents a common finding on magnetic resonance imaging (MRI) of the knee and other joints, which can occur as a primary pathology or as a secondary phenomenon of various bone and joint pathologies. This article reviews the terminology, definition, pathology and differential diagnosis of bone marrow edema of the knee taking into consideration current concepts.
Subject(s)
Bone Marrow Diseases , Bone Marrow , Humans , Bone Marrow/pathology , Knee Joint/pathology , Knee/pathology , Bone Marrow Diseases/diagnosis , Bone Marrow Diseases/pathology , Magnetic Resonance Imaging/methods , Edema/diagnosis , Edema/pathology , SyndromeABSTRACT
This study investigates whether infrapatellar fat pad (IPFP) elasticity is associated with anterior knee pain in patients with knee osteoarthritis (KOA). The IPFP elasticity of 97 patients with KOA (Kellgren and Lawrence [KL] grades of the femorotibial and patellofemoral joints ≥ 2 and ≤ 2, respectively), aged 46-86 years, was evaluated via shear wave speed using ultrasound elastography. The patients were divided into two groups according to the presence or absence of anterior knee pain. Univariate analyses were used to compare patient age, sex, femorotibial KL grade, magnetic resonance imaging findings (Hoffa, effusion synovitis, bone marrow lesion scores, and IPFP size), and IPFP elasticity between the groups. Multivariate logistic regression analyses were subsequently performed using selected explanatory variables. IPFP elasticity was found to be associated with anterior knee pain in the univariate (p = 0.007) and multivariate (odds ratio: 61.12, 95% CI 1.95-1920.66; p = 0.019) analyses. Anterior knee pain is strongly associated with stiffer IPFPs regardless of the femorotibial KL grade, suggesting that ultrasound elastography is useful for the diagnosis of painful IPFP in patients with KOA.
Subject(s)
Cartilage Diseases , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/complications , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/pathology , Knee Joint/diagnostic imaging , Knee Joint/pathology , Knee/pathology , Adipose Tissue/diagnostic imaging , Adipose Tissue/pathology , Pain/diagnostic imaging , Pain/etiology , Pain/pathology , Magnetic Resonance Imaging/methods , Cartilage Diseases/pathologyABSTRACT
PURPOSE: To investigate the current preferences regarding the work-up and treatment choices of juvenile osteochondritis dissecans (JOCD) of the knee, ankle and elbow among orthopaedic surgeons. METHODS: An international survey was set up for all European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) members, which assessed various questions on diagnosis and treatment of JOCD of different joints. Respondents answered questions for one or more joints, based on their expertise. Proportions of answers were calculated and compared between joints. Consensus was defined as more than 75% agreement on an item; disagreement was defined as less than 25% agreement. RESULTS: Fifty physicians responded to the survey, of whom forty-two filled out the questions on the knee, fourteen on the ankle and nine on the elbow. Plain radiography and MRI were the most used imaging modalities for the assessment and follow-up of JOCD in the knee and ankle, but not for the elbow. MRI was also the preferred method to assess the stability of a lesion in the knee and ankle. There was universal agreement on activity and/or sports restriction as the non-operative treatment of choice for JOCD. Size, stability and physeal closure were the most important prognostic factors in determining the operative technique for the elbow. For the knee, these factors were size and stability and for the ankle, these were size and location. CONCLUSION: Activity and/or sports restriction was the non-operative treatment of choice. Furthermore, plain radiography and MRI were the preferred imaging modalities for the knee and ankle, but not for the elbow. For determining the operative technique, physicians agreed that the size of the lesion is an important prognostic factor in all joints. These findings help us understand how juvenile osteochondritis dissecans is treated in current practice and may provide opportunities for improvement. LEVEL OF EVIDENCE: Level V.
Subject(s)
Osteochondritis Dissecans , Physicians , Humans , Osteochondritis Dissecans/diagnosis , Osteochondritis Dissecans/surgery , Ankle/pathology , Elbow , Knee/pathology , Knee Joint/surgery , Knee Joint/pathologyABSTRACT
The existing methods for analyzing patellofemoral (PF) osteoarthritis (OA) are limited. Our purpose was to clarify the frequency, localization, and morphological progression of PFOA by observing three-dimensional (3D) magnetic resonance (MR) images from a cohort population. The subjects were 561 patients aged 30-79 years from the Kanagawa Knee Study who had not visited a hospital for more than three consecutive months for knee symptoms. MR images of the PF joints, separated into the medial and lateral types, were presented in order of the highest to lowest patella cartilage area ratios. Cartilage defects in the patella were detected in 37 subjects (6.6%). Medial lesions (4.6%) were significantly more frequent than lateral lesions (2.0%) (p < 0.01). For both medial and lateral lesions, the patellar cartilage defects were divided into confined and unconfined types. The 3D MR images of the PF joint showed that the patellar cartilage defect occurred along each ridge of the femoral trochlea. The 3D MR images revealed a 6.6% prevalence of patellar cartilage defects, higher in the medial than lateral regions. The 3D MR images can easily determine PF morphology and cartilage defect location, making them useful in understanding the pathophysiology and etiology of PFOA.
Subject(s)
Bone Diseases , Cartilage Diseases , Cartilage, Articular , Osteoarthritis, Knee , Patellofemoral Joint , Humans , Patellofemoral Joint/diagnostic imaging , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/pathology , Knee Joint/diagnostic imaging , Knee Joint/pathology , Knee/pathology , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/pathology , Magnetic Resonance Imaging/methods , Patella/diagnostic imaging , Patella/pathology , Cartilage Diseases/pathology , Bone Diseases/pathologyABSTRACT
BACKGROUND: This case reports the synchronous diagnosis of two rare unrelated diseases; leiomyosarcoma and tenosynovial giant cell tumor of the knee. It focuses on the challenges of diagnosing tenosynovial giant cell tumor, including cognitive biases in clinical medicine that delay diagnosis. It also demonstrates the pathogenic etiology of tenosynovial giant cell tumor, evidenced by the transient deterioration of the patients' knee symptoms following the administration of prophylactic granulocyte colony-stimulating factor given as part of the chemotherapeutic regime for leiomyosarcoma. CASE PRESENTATION: A 37-year-old Caucasian man presented with a left groin lump and left knee pain with swelling and locking. Investigations including positron emission tomography-computed tomography and biopsy revealed leiomyosarcoma in a lymph node likely related to the spermatic cord, with high-grade uptake in the left knee that was presumed to be the primary site. His knee symptoms temporarily worsened each time granulocyte colony-stimulating factor was administered with each cycle of chemotherapy for leiomyosarcoma to help combat myelosuppressive toxicity. Subsequent magnetic resonance imaging and biopsy of the knee confirmed a tenosynovial giant cell tumor. His knee symptoms relating to the tenosynovial giant cell tumor improved following the completion of his leiomyosarcoma treatment. CONCLUSIONS: Tenosynovial giant cell tumor remains a diagnostic challenge. We discuss the key clinical features and investigations that aid prompt diagnosis. The National Comprehensive Cancer Network clinical practice guidelines for soft tissue sarcoma have recently been updated to include the pharmacological management of tenosynovial giant cell tumor. Our case discussion provides an up-to-date review of the evidence for optimal management of patients with tenosynovial giant cell tumor, with a particular focus on novel pharmacological options that exploit underlying pathogenesis.
Subject(s)
Giant Cell Tumor of Tendon Sheath , Leiomyosarcoma , Male , Humans , Adult , Leiomyosarcoma/pathology , Giant Cell Tumor of Tendon Sheath/diagnostic imaging , Giant Cell Tumor of Tendon Sheath/pathology , Knee Joint/pathology , Knee/pathology , Granulocyte Colony-Stimulating FactorABSTRACT
OBJECTIVES: To explore factors that were associated with meniscus volume in knees free of radiographic osteoarthritis (OA) features and symptoms of OA. METHODS: In the third Rotterdam Study cohort, clinical, radiographic, and magnetic resonance data were obtained at baseline (BL) and after 5 years of follow-up. Meniscus volumes and their change over time were calculated after semi-automatic segmentation on Magnetic Resonance Imaging. Knees with radiographic OA features (Kellgren and Lawrence>0) or clinical diagnosis of OA (American College of Rheumatology) at BL were excluded. Ten OA risk factors were adjusted in the multivariable analysis (generalized estimating equations), treating two knees within subjects as repeated measurements. RESULTS: From 1065 knees (570 subjects), the average (standard deviation) age and Body mass index (BMI) of included subjects were 54.3 (3.7) years and 26.5 (4.4) kg/m2. At BL, nine factors (varus alignment, higher BMI, meniscus pathologies, meniscus extrusion, cartilage lesions, injury, greater physical activity level, quadriceps muscle strength, and higher age) were significantly associated with greater meniscus volume. Five factors (injury, meniscus pathologies, meniscus extrusion, higher age, and change of BMI) were significantly associated with meniscus volume loss. CONCLUSIONS: Modifiable factors (varus alignment, BMI, physical activity level, and quadriceps muscle strength) and non-modifiable factors (higher age, injury, meniscus pathologies, meniscus extrusion, and cartilage lesions) were all associated with meniscus volume or meniscus volume loss over time.
Subject(s)
Meniscus , Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/pathology , Radiography , Knee/pathology , Knee Joint/diagnostic imaging , Knee Joint/pathology , Magnetic Resonance Imaging/methods , Menisci, Tibial/diagnostic imaging , Menisci, Tibial/pathology , Meniscus/pathologyABSTRACT
OBJECTIVE: The present study aims to compare the presence and severity of patellofemoral osteoarthritis between patients with root lesions and non-root lesions. DESIGN: A total of 102 patients were included in this study (51 root lesions and 51 non-root lesions). The root lesion cohort was matched to a non-root lesion cohort based on sex, body mass index, and age at the time of surgery. Radiographic evaluation with modified Outerbridge scoring of MRI of the knee was performed to determine the severity of degeneration of the knee joint preoperatively. Mann-Whitney and Independent t tests were used to compare the groups. RESULTS: The root lesion group had statistically greater Outerbridge patella scores (M = 2.45 ± 1.12) and trochlear scores (M = 2.27 ± 1.37) than the non-root lesion patients (M = 1.78 ± 1.30, P = 0.006, and M = 1.55 ± 1.40, P = 0.010, respectively). When using a new scale for grading patellofemoral arthritis, the root lesion group had statistically greater scores (M = 8.33 ± 3.38) than the non-root lesion patients (M = 5.67 ± 3.07) (P < 0.001). CONCLUSION: Patients with root lesions have a greater degree of patellofemoral cartilage lesions than patients without root lesions. The presence of cartilage lesions preoperatively in root lesion patients has presented the question of whether repair is worthwhile or if one should delay surgery until arthroplasty is indicated. Future research should be carried out on outcomes of root repair surgery in patients with patellofemoral cartilage lesions, in addition to considering the patient's age, activity level, and other risk factors.
Subject(s)
Knee Joint , Osteoarthritis, Knee , Humans , Knee Joint/surgery , Menisci, Tibial/surgery , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/pathology , Knee/pathology , Magnetic Resonance ImagingABSTRACT
A young girl received a diagnosis of septic arthritis of the knee unresponsive to standard medical and surgical treatment. We report the patient's clinical journey with clinical commentary throughout, underlying the importance of differential diagnosis that may open several scenarios and a different final diagnosis accordingly. Finally, we will discuss the treatment and management of the patient's final diagnosis.
Subject(s)
Arthritis, Infectious , Knee , Rheumatic Fever , Female , Humans , Cardiologists , Diagnosis, Differential , Knee/pathology , Knee Joint , Pain , Adolescent , Arthritis, Infectious/diagnosis , Fever/etiology , BiomarkersABSTRACT
Objectives: 1) To characterize the inflammatory proteome of synovial fluid (SF) from patients with Psoriatic Arthritis (PsA) using a high-quality throughput proteomic platform, and 2) to evaluate its potential to stratify patients according to clinical features. Methods: Inflammatory proteome profile of SF from thirteen PsA patients with active knee arthritis were analyzed using proximity extension assay (PEA) technology (Olink Target 96 Inflammation panel). Four patients with OA were included as control group. Results: Seventy-nine inflammation-related proteins were detected in SF from PsA patients (SF-PsA). Unsupervised analyzes of the molecular proteome profile in SF-PsA identified two specific phenotypes characterized by higher or lower levels of inflammation-related proteins. Clinically, SF-PsA with higher levels of inflammatory proteins also showed increased systemic inflammation and altered glucose and lipid metabolisms. Besides, SF from PsA patients showed 39 out of 79 proteins significantly altered compared to SF-OA specifically related to cell migration and inflammatory response. Among these, molecules such as TNFα, IL-17A, IL-6, IL-10, IL-8, ENRAGE, CCL20, TNFSF-14, OSM, IFNγ, MCP-3, CXCL-11, MCP4, CASP-8, CXCL-6, CD-6, ADA, CXCL-10, TNFß and IL-7 showed the most significantly change. Conclusion: This is the first study that characterizes the inflammatory landscape of synovial fluid of PsA patients by analyzing a panel of 92 inflammatory proteins using PEA technology. Novel SF proteins have been described as potential pathogenic molecules involved in the pathogenesis of PsA. Despite the flare, inflammatory proteome could distinguish two different phenotypes related to systemic inflammation and lipid and glucose alterations.
Subject(s)
Arthritis, Psoriatic , Synovial Fluid , Synovial Fluid/chemistry , Arthritis, Psoriatic/immunology , Arthritis, Psoriatic/metabolism , Humans , Male , Female , Adult , Middle Aged , Synoviocytes/metabolism , Cytokines/analysis , Knee/pathologyABSTRACT
BACKGROUND: Bone neoplasms are usually misdiagnosed causing a delay in their treatment. Bone neoplasms are usually confused with tendinitis, 31% of the cases corresponds to osteosarcomas and in 21% to Ewing's sarcomas. OBJECTIVE: To create a clinical-radiographic instrument of high diagnostic suspicion of knee bone neoplasms to prevent a delay in diagnosis. METHOD: A clinimetric study (sensitivity, consistency and validity) was performed in the bone tumor service, Hospital de Ortopedia de la Unidad Médica de Alta Especialidad Dr. Victorio de la Fuente Narváez, Instituto Mexicano del Seguro Social, in México City. RESULTS: Characteristics of 153 patients were collected. For the sensitivity phase, 3 domains (signs, symptoms, and radiology) and 12 items were included. Consistency was evaluated with ICC (0.944), 95%CI (0.865-0.977), p < 0.001 and a-Cronbach (0.863). Index obtained a sensitivity of 0.80 and a specificity of 0.882 were obtained. The positive predictive value of the test was 66.6% and the negative predictive value was 93.75%. The positive likelihood ratio was 6.8 and the negative likelihood ratio was 0.2. Validity was evaluated using r-Pearson (0.894; p < 0.001). CONCLUSIONS: A high suspicion clinical-radiographic index was designed to detect malignant knee tumors with adequate sensitivity, specificity, appearance, content, criteria, and construct validity.
ANTECEDENTES: Los tumores óseos suelen ser subdiagnosticados, provocando un retraso en su tratamiento. El diagnóstico erróneo más frecuente es tendinitis, en el cual el 31% corresponden a osteosarcomas y el 21% a sarcomas de Ewing. OBJETIVO: Crear un instrumento clínico-radiográfico de alta sospecha diagnóstica de tumores óseos de rodilla. MÉTODO: Se realizó un estudio clinimétrico (sensibilidad, consistencia y validez) en el servicio de tumores óseos del Hospital de Ortopedia de la Unidad Médica de Alta Especialidad Dr. Victorio de la Fuente Narváez, Instituto Mexicano del Seguro Social, en Ciudad de México. RESULTADOS: El índice se realizó tomando las características de 153 pacientes. Para la fase de sensibilidad se incluyeron tres dominios (signos, síntomas y radiología) y 12 ítems. La consistencia se evaluó con coeficiente de correlación intraclase (0.944), intervalo de confianza del 95% (0.865-0.977), p < 0.001 y α de Cronbach (0.863). Se obtuvo una sensibilidad del instrumento de 0.80 y una especificidad de 0.882. El valor predictivo positivo de la prueba fue del 66.6% y el valor predictivo negativo fue de 93.75%. La razón de verosimilitud positiva fue de 6.8 y la razón de verosimilitud negativa fue de 0.2. La validez se evaluó mediante r-Pearson (0.894; p < 0.001). CONCLUSIONES: Se diseñó un índice clínico-radiográfico de alta sospecha para detectar tumores malignos de rodilla con adecuada sensibilidad, especificidad y validez de apariencia, de contenido, de criterio y de constructo.
Subject(s)
Bone Neoplasms , Knee , Humans , Bone Neoplasms/diagnostic imaging , Mexico , Predictive Value of Tests , Retrospective Studies , Knee/diagnostic imaging , Knee/pathologyABSTRACT
The cause of knee osteoarthritis (OA) and knee pain associated with OA is not well understood. Periarticular cystic lesions and bursae around the knee are among the most common morphologic features identified on MRI in the setting of OA. Despite widespread association of these lesions with knee OA and their inclusion in semiquantitative MRI scoring assessment systems for knee OA, the role that these lesions play in the development of knee pain and OA remains uncertain. In this discussion, we review the cystic lesions and bursae most commonly associated with OA of the knee, examine their relation and role in whole organ imaging assessments of OA, and present the literature investigating the associations of periarticular cysts and cyst-like lesions with knee pain and OA.
Subject(s)
Osteoarthritis, Knee , Humans , Osteoarthritis, Knee/diagnostic imaging , Osteoarthritis, Knee/pathology , Knee Joint/diagnostic imaging , Knee Joint/pathology , Knee/pathology , Bursa, Synovial/pathology , Magnetic Resonance Imaging/methods , PainABSTRACT
Arthrofibrosis, which is characterized by excessive scar tissue and limited motion, can complicate the daily functioning of patients after total knee arthroplasty (TKA). Molecular hallmarks of arthrofibrosis include pathologic accumulation of myofibroblasts and disproportionate collagen deposition. Epigenetic mechanisms, including posttranslation modification of histones, control gene expression and may regulate fibrotic events. This study assessed the role of the bromodomain and extra-terminal (BET) proteins on myofibroblast differentiation. This group of epigenetic regulators recognize acetylated lysines and are targeted by a class of drugs known as BET inhibitors. RNA-seq analysis revealed robust mRNA expression of three BET members (BRD2, BRD3, and BRD4) while the fourth member (BRDT) is not expressed in primary TKA knee outgrowth fibroblasts. RT-qPCR and western blot analyses revealed that BET inhibition with the small molecule JQ1 impairs TGFß1-induced expression of ACTA2, a key myofibroblast marker, in primary outgrowth knee fibroblasts. Similarly, JQ1 administration also reduced COL3A1 mRNA levels and collagen deposition as monitored by picrosirius red staining. Interestingly, the inhibitory effects of JQ1 on ACTA2 mRNA and protein expression, as well as COL3A1 expression and collagen deposition, were paralleled by siRNA-mediated depletion of BRD4. Together, these data reveal that BRD4-mediated epigenetic events support TGFß1-mediated myofibroblast differentiation and collagen deposition as seen in arthrofibrosis. To our knowledge, these are the first studies that assess epigenetic regulators and their downstream events in the context of arthrofibrosis. Future studies may reveal clinical utility for drugs that target epigenetic pathways, specifically BET proteins, in the prevention and treatment of arthrofibrosis.
Subject(s)
Knee , Myofibroblasts , Transcription Factors , Humans , Azepines/pharmacology , Cell Cycle Proteins/genetics , Collagen/metabolism , Epigenesis, Genetic , Fibroblasts/metabolism , Knee/pathology , Myofibroblasts/metabolism , Nuclear Proteins/metabolism , RNA, Messenger/metabolism , Transcription Factors/metabolismABSTRACT
Tenosynovial giant cell tumors (TSGCT) are benign tumors originating from the synovial joint, bursa, or tendon sheath. Localized pigmented villonodular synovitis (PVNS), a subtype of TSGCT, commonly affects the hands and feet and has also been reported in the literature in the knee joint. There is sparse literature on localized PVNS arising specifically from meniscal tissue. We present a case report of a 17-year- old male with symptoms and MRI findings consistent with a lateral meniscus tear. Intraoperatively, the patient was found to have a mass originating from the torn meniscal tissue, which was confirmed by pathology to be a TSGCT. We performed a literature review of intra-articular localized PVNS within the knee presenting as a meniscal tear.