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Acta Biomaterialia May 2024Osteoarthritis (OA) poses significant therapeutic challenges, particularly OA that affects the hand. Currently available treatment strategies are often limited in terms...
Osteoarthritis (OA) poses significant therapeutic challenges, particularly OA that affects the hand. Currently available treatment strategies are often limited in terms of their efficacy in managing pain, regulating invasiveness, and restoring joint function. The APRICOT implant system developed by Aurora Medical Ltd (Chichester, UK) introduces a minimally invasive, bone-conserving approach for treating hand OA (https://apricot-project.eu/). By utilizing polycarbonate urethane (PCU), this implant incorporates a caterpillar track-inspired design to promote the restoration of natural movement to the joint. Surface modifications of PCU have been proposed for the biological fixation of the implant. This study investigated the biocompatibility of PCU alone or in combination with two surface modifications, namely dopamine-carboxymethylcellulose (dCMC) and calcium-phosphate (CaP) coatings. In a rat soft tissue model, native and CaP-coated PCU foils did not increase cellular migration or cytotoxicity at the implant-soft tissue interface after 3 d, showing gene expression of proinflammatory cytokines similar to that in non-implanted sham sites. However, dCMC induced an amplified initial inflammatory response that was characterized by increased chemotaxis and cytotoxicity, as well as pronounced gene activation of proinflammatory macrophages and neoangiogenesis. By 21 d, inflammation subsided in all the groups, allowing for implant encapsulation. In a rat bone model, 6 d and 28 d after release of the periosteum, all implant types were adapted to the bone surface with a surrounding fibrous capsule and no protracted inflammatory response was observed. These findings demonstrated the biocompatibility of native and CaP-coated PCU foils as components of APRICOT implants. STATEMENT OF SIGNIFICANCE: Hand osteoarthritis treatments require materials that minimize irritation of the delicate finger joints. Differing from existing treatments, the APRICOT implant leverages polycarbonate urethane (PCU) for minimally invasive joint replacement. This interdisciplinary, preclinical study investigated the biocompatibility of thin polycarbonate urethane (PCU) foils and their surface modifications with calcium-phosphate (CaP) or dopamine-carboxymethylcellulose (dCMC). Cellular and morphological analyses revealed that both native and Ca-P coated PCU elicit transient inflammation, similar to sham sites, and a thin fibrous encapsulation in soft tissues and on bone surfaces. However, dCMC surface modification amplified initial chemotaxis and cytotoxicity, with pronounced activation of proinflammatory and neoangiogenesis genes. Therefore, native and CaP-coated PCU possess sought-for biocompatible properties, crucial for patient safety and performance of APRICOT implant.
PubMed: 38815684
DOI: 10.1016/j.actbio.2024.05.042 -
Journal of Chromatography. B,... Jul 2024After a revision surgery, approximately 1-2 % of patients will develop a periprosthetic joint infection (PJI). During the revision surgery, the infected prosthesis is...
After a revision surgery, approximately 1-2 % of patients will develop a periprosthetic joint infection (PJI). During the revision surgery, the infected prosthesis is removed, a debridement is performed and a new or temporary spacer is placed. Additionally, patients are treated with antibiotics during and after the surgery. Adequate exposure of the administered antibiotic to the pathogen is of crucial importance during the treatment of any infection. Inadequately low concentrations are associated with an increase in antibiotic resistance, antibiotic related side effects, treatment failures and prolonged infections. While high concentrations may lead to serious adverse events and potential lasting damage. Despite the importance of optimal dosing, there is a lack of knowledge with respect to the correlation between the plasma concentrations and target site concentrations of the antibiotics. Two of the commonly administered antimicrobial agents during the arthroplasty exchange are cefuroxime and flucloxacillin. Therefore, an accurate, specific, and sensitive quantification method is required in order to assess pharmacokinetics of cefuroxime and flucloxacillin in synovial tissue and bone. The aim of this study is to develop and validate a quantification method for the measurement of cefuroxime and flucloxacillin in human synovial tissue and bone using the UPC-MS/MS conform Food and Drug Administration guidelines. The method was found linear for both compounds in both matrices (r > 0.990) from 1 µg/g to 20 µg/g, except for cefuroxime in bone, which was validated from 1 µg/g to 15 µg/g. We developed and validated a quantification method for cefuroxime and flucloxacillin in synovial tissue and bone using a simple sample preparation and a short analysis run time of 5.0 min, which has been already successfully applied in a clinical study. To our knowledge, no methods have been described earlier for the simultaneous quantification of cefuroxime and flucloxacillin in synovial tissue and bone.
Topics: Humans; Tandem Mass Spectrometry; Cefuroxime; Chromatography, High Pressure Liquid; Linear Models; Reproducibility of Results; Floxacillin; Anti-Bacterial Agents; Bone and Bones; Synovial Membrane; Limit of Detection
PubMed: 38815354
DOI: 10.1016/j.jchromb.2024.124169 -
Cellular and Molecular Biology... May 2024The study aimed to explore the pathogenesis of secondary frozen shoulder and its influence on synovium tissue and angiogenesis by constructing a rat secondary frozen...
The study aimed to explore the pathogenesis of secondary frozen shoulder and its influence on synovium tissue and angiogenesis by constructing a rat secondary frozen shoulder model along with transforming growth factor. 40 healthy male rats aged 8 weeks were divided into Sham group (n=10, no modeling treatment), Control group (n=10, modeling treatment), Low group (n=10, modeling treatment, and 10 mL/d transforming growth factor), and High group (n=10, modeling treatment, and 20 mL/d transforming growth factor). Hematoxylin and Eosin (HE) method was used for histological detection, and Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and immunohistochemical staining method were adopted to detect the expression of Matrix metalloproteinase-14 (MMP-14), mitogen-activated protein kinase (p38MAPK), and Vascular endothelial growth factor (VEGF). Compared with Sham group, the range of abduction and external rotation of rat glenohumeral joint in Control group, Low group, and High group was significantly reduced, and High group had the smallest range. Compared with the Sham group, the synovium in the Control group, the Low group, and the High group had obvious hyperplasia, and the blood vessels were significantly increased. Immunohistochemical staining and RT-PCR results showed that compared with Sham group, MMP-14, p38 MAPK, and VEGF in Control group, Low group, and High group all increased significantly, among which High group increased most. The secondary frozen shoulder is mainly manifested as synovial hyperplasia and increased blood vessels, which are related to the induction of MMP-14, p38 MAPK, and VEGF by transforming growth factor, which reveals the pathogenesis of secondary frozen shoulder to a certain extent, and lays a foundation for subsequent clinical treatment of secondary frozen shoulder.
Topics: Animals; Male; Synovial Membrane; Disease Models, Animal; Vascular Endothelial Growth Factor A; p38 Mitogen-Activated Protein Kinases; Shoulder Joint; Bursitis; Rats; Neovascularization, Pathologic; Rats, Sprague-Dawley; Gene Expression Regulation; Angiogenesis
PubMed: 38814204
DOI: 10.14715/cmb/2024.70.5.39 -
Histology and Histopathology May 2024The clinical outcome of most cancer patients depends on the stage of the primary tumor, the lymph node status, and if distant metastases are present. According to the... (Review)
Review
The clinical outcome of most cancer patients depends on the stage of the primary tumor, the lymph node status, and if distant metastases are present. According to the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC), the Tumor Node Metastasis (TNM) classification of malignant tumors requires the examination of a minimum number of regional lymph nodes for each type of cancer to fulfill the criteria of high-quality surgical oncology. Due to the daily challenge of collecting an appropriate number of lymph nodes and time constraints when processing and assessing tissue samples, pathologists may be tempted to identify every histological lymphoid structure mimicking a lymph node as a "true" lymph node. Faced with this issue, we propose to resolve it by specifying histological characteristics to differentiate lymphoid aggregates from "true" lymph nodes. To find a minimum consensus, we suggest defining as lymph nodes only those lymphoid structures composed of lymphoid cells encapsulated by a complete or incomplete fibrous capsule.
PubMed: 38813797
DOI: 10.14670/HH-18-760 -
Indian Journal of Orthopaedics Jun 2024Neurofibromatosis is an autosomal-dominant multi-system disease affecting the nervous, integumentary, ocular, and musculoskeletal systems. In the small number of...
Neurofibromatosis is an autosomal-dominant multi-system disease affecting the nervous, integumentary, ocular, and musculoskeletal systems. In the small number of reported cases, the cause was either atraumatic or an intra-articular neurofibroma. Only a couple of articles in medical literature have reported synovial and capsular hemangioma originating within the hip joint. In this article, we present a rare case of pathological hip dislocation in a neurofibromatosis patient secondary to capsular hemangioma that would be reported for the first time in medical literature. We present the case of a 20-year-old female, resident of Karachi, who presented to the outpatient clinic with pain in the left hip join and inability to bear weight on left leg for 1 week. Diagnosed as a case of posterior hip dislocation after physical examination and imaging, her dislocation was reduced by the Allis method. This maneuver, however, was unsuccessful. Ultimately, the joint was reduced with open reduction via Steinmann pin because post-reduction hip joint was unstable to be contained into the acetabulum; therefore, Steinmann pin was used. The biopsy specimen taken from joint capsule and femoral neck during the surgery revealed cavernous hemangioma within the capsule. Hence, the etiology of posterior hip dislocation was attributed to the presence of capsular hemangioma within the hip joint. The surgery proved successful. The patient had remarkable recovery. The Steinmann pin was removed at 6 weeks, full weight-bearing started at 3 months, and range of motion extended from 0 to 90 degrees at 1 year with imaging studies showing a normally placed hip joint. The presented case reports an unusual etiology of a rare pathology occurring in association with a common genetic disease. It focuses on the importance of thorough examination and extensive relevant investigations in patients presenting with rare pathologies. These practices not only expedite the diagnosis and treatment of such patients, but can also reveal unusual etiologies responsible for uncommon pathologies. This case would help widen the differential diagnosis and treatment strategies of the physicians while dealing with neurofibromatosis patients with pathological hip dislocation. This is a case report having Level of Evidence 4 in accordance with the levels developed by the Centre of Evidence Based Medicine (CEBM) for treatment.
PubMed: 38812877
DOI: 10.1007/s43465-024-01166-8 -
Indian Journal of Orthopaedics Jun 2024Rubber band constriction syndrome has been described in the literature, although there are very few case reports. Non-healing recurrent tenosynovitis and synovitis of...
Rubber band constriction syndrome has been described in the literature, although there are very few case reports. Non-healing recurrent tenosynovitis and synovitis of the wrist joint demonstrating a circular rubber band on imaging has not been described before. Imaging studies showed retained circular band deep to the extensor tendons, embedded within the joint capsule. Surgical removal of the band by open incision led to a dramatic improvement in the outcome of the patient. V.
PubMed: 38812874
DOI: 10.1007/s43465-024-01151-1 -
Journal of Orthopaedic Surgery and... May 2024To investigate the effect and underlying mechanism of umbilical cord blood-mononuclear cells (UCB-MNCs) in treating knee osteoarthritis (KOA) in rabbits.
BACKGROUND
To investigate the effect and underlying mechanism of umbilical cord blood-mononuclear cells (UCB-MNCs) in treating knee osteoarthritis (KOA) in rabbits.
METHODS
A rabbit KOA model was prepared by anterior cruciate ligament transection (ACLT). Fifty New Zealand white rabbits were randomly divided into the control group, model group, sodium hyaluronate (SH) group, platelet-rich plasma (PRP) group and UCB-MNC group. Knee injections were performed once a week for five consecutive weeks. The gross view of the knee joint, morphology of knee cartilage and structural changes in the knee joint were observed on CT scans, and graded by the Lequesne MG behavioral score and the Mankin score. TNF-α and IL-1β levels in the synovial fluid of the knee were measured by the enzyme-linked immunosorbent assay (ELISA). Expression levels of MMP-13 and COL-II in the knee cartilage were detected by Western blotting and qRT-PCR.
RESULTS
The Lequesne MG behavioral score and the Mankin score were significantly higher in the model group than those in the control group (P < 0.05). Rabbits in the SH, PRP and UCB-MNC groups had sequentially lower scores than those in the model group. Imaging features of KOA were more pronounced in the model group than in the remaining groups. CB-MNC significantly relieved KOA, compared to SH and PRP. Significantly higher levels of TNF-α and IL-1β in the synovial fluid of the knee, and up-regulated MMP-13 and down-regulated COL-II in the knee cartilage were detected in the model group than in the control group. These changes were significantly reversed by the treatment with SH, PRP and UCB-MNCs, especially UCB-MNCs.
CONCLUSION
Injections of UCB-MNCs into knees protect the articular cartilage and hinder the progression of KOA in rabbits by improving the local microenvironment at knee joints.
Topics: Animals; Rabbits; Osteoarthritis, Knee; Fetal Blood; Disease Models, Animal; Male; Leukocytes, Mononuclear; Interleukin-1beta; Tumor Necrosis Factor-alpha; Synovial Fluid; Platelet-Rich Plasma; Cord Blood Stem Cell Transplantation; Random Allocation
PubMed: 38811966
DOI: 10.1186/s13018-024-04815-8 -
Journal of Shoulder and Elbow Surgery May 2024The pathophysiology of frozen shoulder (FS) involves abnormal expressions of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) that...
BACKGROUND
The pathophysiology of frozen shoulder (FS) involves abnormal expressions of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMPs) that lead capsular fibrosis. However, there has been little concern for why diabetic FS has more protracted fibrotic condition. The objective of this study was to compare the expression levels of MMPs and TIMPs in the joint capsule of patients with diabetic and non-diabetic FS.
MATERIALS AND METHODS
Samples of capsular tissue were collected from 20 patients with FS (10 diabetic patients; diabetic group, and 10 non-diabetic patients; non-diabetic group) and 10 patients (control group) with chronic anterior shoulder instability. Quantitative real-time RT-PCR and Western blot analysis were performed to determine the expression levels of mRNA and protein for MMP-1, 3, 9, 13, 14, and TIMP-1, 2.
RESULTS
The results of quantitative real-time RT-PCR showed significantly higher expression levels of all MMPs and TIMP-1 and significantly lower expression levels of TIMP-2 in the joint capsule of patients in the diabetic or non-diabetic groups compared with the control group. Significantly higher expression levels of MMP-1, 9, 14, and TIMP-1 were detected in the diabetic group compared with the non-diabetic group. The results of Western blot analysis showed significantly higher levels of MMP-3, 13, 14, and TIMP-1 in the joint capsule of patients in the diabetic or non-diabetic groups compared with the control group. However, no significant differences of protein levels of them were observed between diabetic and non-diabetic groups.
CONCLUSIONS
The findings of this study demonstrate the potential involvement of MMP-1 and 9 in the pathophysiology of diabetic FS. These findings may be helpful in identification of therapeutic targets for development of novel treatments for this protracted chronic fibrosing condition.
PubMed: 38810916
DOI: 10.1016/j.jse.2024.03.062 -
International Immunopharmacology Jul 2024Defective clearance of apoptotic cells due to impaired efferocytosis sustains error in self-tolerance that exacerbates rheumatoid arthritis (RA). However, the molecular...
IL-17A/IL-17RA interaction blockade sensitizes synovial macrophages to efferocytosis and PD-L1 signaling via rewiring STAT-3/ADAM17/MERTK axis in rheumatoid arthritis animal model.
Defective clearance of apoptotic cells due to impaired efferocytosis sustains error in self-tolerance that exacerbates rheumatoid arthritis (RA). However, the molecular determinant that directly or specifically impairs efferocytosis in RA is not yet studied. We identified a new perspective that IL-17A significantly impedes efferocytosis via preferential activation of the JAK/STAT-3/ADAM17 signaling axis. In contrast, disruption of the IL-17A/IL-17RA interaction using cyanidin or silencing of IL-17RA obstructed JAK/STAT-3 activation that further abolished ADAM17 expression. Subsequent depletion of ADAM17 inhibited the shedding of Mer tyrosine kinase receptor (MERTK), which significantly increased apoptotic cell intake and restored efferocytosis in adjuvant-induced arthritic (AA) model. Concomitantly, the amplification of the efferocytosis process due to IL-17A/IL-17RA interaction disruption was sensitive to mitochondrial fission mediated via Drp-1 phosphorylation downstream of STAT-3 inhibition. As expected, cyanidin treated AA synovial macrophages that exhibited increased efferocytosis demonstrated a phenotypic shift towards CD163 anti-inflammatory phenotype in a STAT-5 dependent manner. Similar results were obtained in IL-17A-sensitized AA synovial macrophages treated with S3I-201 (a STAT-3 inhibitor) indicating that IL-17A influences efferocytosis via the STAT-3 pathway. In view of our previous work where cyanidin restored Th17/Treg balance, our present investigation fulfils a critical gap by providing scientific validation that cyanidin escalated PD-L1 expression during the efferocytosis process that could have impacted the restoration of Th17/Treg balance in an AA model. Together, these data corroborate the hypothesis that IL-17A signaling can impair efferocytosis via regulating STAT-3/ADAM17/FL-MERTK axis and that its inhibition can amplify a pro-resolution signal against RA progression.
Topics: Interleukin-17; Animals; STAT3 Transcription Factor; Arthritis, Rheumatoid; Macrophages; Signal Transduction; B7-H1 Antigen; Mice; Receptors, Interleukin-17; Anthocyanins; Arthritis, Experimental; Humans; Disease Models, Animal; Phagocytosis; Male; Synovial Membrane; Mice, Inbred C57BL; Apoptosis; Efferocytosis
PubMed: 38810305
DOI: 10.1016/j.intimp.2024.112343 -
Current Rheumatology Reviews 2024Synovial hemangioma is a benign soft-tissue tumor of vascular origin. Hemangioma only accounts for 1% of all bone lesions and is mostly an incidental finding among the...
INTRODUCTION
Synovial hemangioma is a benign soft-tissue tumor of vascular origin. Hemangioma only accounts for 1% of all bone lesions and is mostly an incidental finding among the primary skeleton tumors. A delay in diagnosis results in joint degeneration and osteoarthritic damage because of infiltrating tumor growth.
CASE PRESENTATION
We presented a rare case of an intra-articular synovial hemangioma in a 13- year-old pediatric patient who was asymptomatic for 5 years. She attended orthopedics OPD at AIIMS, Mangalagiri. Surgical excision of the mass and partial synovectomy was done. Synovial hemangioma came out to be the diagnosis following a histologic study.
CONCLUSION
As radiography has limited diagnostic ability, synovial hemangiomas are difficult and challenging to identify on an outpatient basis. Histological examination and magnetic resonance imaging are extremely helpful. To minimize the hemarthrosis risks, early complete excision can be used as the best treatment modality.
Topics: Humans; Female; Adolescent; Hemangioma; Knee Joint; Synovial Membrane; Arthralgia; Synovectomy; Soft Tissue Neoplasms; Magnetic Resonance Imaging; Edema
PubMed: 38807471
DOI: 10.2174/0115733971266035231123154807