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Medicine Jun 2024Spontaneously ruptured hepatocellular carcinoma (srHCC) is a life-threatening disease. The prognosis of patients with srHCC after hepatectomy remains unclear. This study...
Spontaneously ruptured hepatocellular carcinoma (srHCC) is a life-threatening disease. The prognosis of patients with srHCC after hepatectomy remains unclear. This study aimed to investigate the prognosis and recurrence after hepatectomy in patients with srHCC. From 2015 to 2020, a retrospective analysis of patients with srHCC who underwent hepatectomy was performed, and compared with patients with unruptured HCC. Among the 86 patients with HCC who underwent hepatectomy, 11 had srHCC. The median tumor size in the ruptured group was significantly larger than that in the unruptured group (P = .001). The incidence rate of vascular invasion and Glisson capsule invasion in the ruptured group was significantly higher than that in the unruptured group. (P = .012 and P < .001, respectively). The American Joint Committee on Cancer was significantly higher in the ruptured group than in the unruptured group (P < .001). In total, 8 (73%) patients in the ruptured group experienced recurrence, whereas the median recurrence-free survival (RFS) and overall survival (OS) periods in the ruptured group were 15 (11-32) and 23 (17-38) months, respectively. In the unruptured group, 34 (45%) patients experienced recurrence, and the median RFS and OS periods were 20 (8-37, P = .099) and 33 (12-51, P = .394) months, respectively. Patients who developed peritoneal metastases were included in the ruptured group (n = 3). Ruptured HCCs exhibit worse oncological outcomes have poorer survival and higher recurrence rates than unruptured HCCs.
Topics: Humans; Liver Neoplasms; Carcinoma, Hepatocellular; Hepatectomy; Male; Female; Middle Aged; Retrospective Studies; Neoplasm Recurrence, Local; Prognosis; Rupture, Spontaneous; Aged; Adult
PubMed: 38875373
DOI: 10.1097/MD.0000000000038555 -
Annales D'endocrinologie Jun 2024Osteoarthritis (OA) is the most common musculoskeletal disease, without any curative treatment. Obesity being the main modifiable risk factor for OA, much attention... (Review)
Review
Osteoarthritis (OA) is the most common musculoskeletal disease, without any curative treatment. Obesity being the main modifiable risk factor for OA, much attention focused on the role of adipose tissues (AT). In addition to the involvement of visceral and subcutaneous AT via systemic ways, many arguments also highlight the involvement of local AT, present in joint tissues. Local AT include intra-articular AT (IAAT), which border the synovium, and bone marrow AT (BMAT) localized within marrow cavities in the bones. This review describes the known features and involvement of IAAT and BMAT in joint homeostasis and OA. Recent findings evidence that alteration in magnetic resonance imaging signal intensity of infrapatellar fat pad can be predictive of the development and progression of knee OA. IAAT and synovium are partners of the same functional unit; IAAT playing an early and pivotal role in synovial inflammation and fibrosis and OA pain. BMAT, whose functions have only recently begun to be studied, is in close functional interaction with its microenvironment. The volume and molecular profile of BMAT change according to the pathophysiological context, enabling fine regulation of haematopoiesis and bone metabolism. Although its role in OA has not yet been studied, the localization of BMAT, its functions and the importance of the bone remodelling processes that occur in OA argue in favour of a role for BMAT in OA.
Topics: Humans; Adipose Tissue; Osteoarthritis; Synovial Membrane; Joints; Osteoarthritis, Knee; Obesity; Bone Marrow; Magnetic Resonance Imaging; Animals
PubMed: 38871517
DOI: 10.1016/j.ando.2024.05.012 -
Arthritis Research & Therapy Jun 2024Kinases are intracellular signalling mediators and key to sustaining the inflammatory process in rheumatoid arthritis (RA). Oral inhibitors of Janus Kinase family (JAKs)...
BACKGROUND
Kinases are intracellular signalling mediators and key to sustaining the inflammatory process in rheumatoid arthritis (RA). Oral inhibitors of Janus Kinase family (JAKs) are widely used in RA, while inhibitors of other kinase families e.g. phosphoinositide 3-kinase (PI3K) are under development. Most current biomarker platforms quantify mRNA/protein levels, but give no direct information on whether proteins are active/inactive. Phosphoproteome analysis has the potential to measure specific enzyme activation status at tissue level.
METHODS
We validated the feasibility of phosphoproteome and total proteome analysis on 8 pre-treatment synovial biopsies from treatment-naive RA patients using label-free mass spectrometry, to identify active cell signalling pathways in synovial tissue which might explain failure to respond to RA therapeutics.
RESULTS
Differential expression analysis and functional enrichment revealed clear separation of phosphoproteome and proteome profiles between lymphoid and myeloid RA pathotypes. Abundance of specific phosphosites was associated with the degree of inflammatory state. The lymphoid pathotype was enriched with lymphoproliferative signalling phosphosites, including Mammalian Target Of Rapamycin (MTOR) signalling, whereas the myeloid pathotype was associated with Mitogen-Activated Protein Kinase (MAPK) and CDK mediated signalling. This analysis also highlighted novel kinases not previously linked to RA, such as Protein Kinase, DNA-Activated, Catalytic Subunit (PRKDC) in the myeloid pathotype. Several phosphosites correlated with clinical features, such as Disease-Activity-Score (DAS)-28, suggesting that phosphosite analysis has potential for identifying novel biomarkers at tissue-level of disease severity and prognosis.
CONCLUSIONS
Specific phosphoproteome/proteome signatures delineate RA pathotypes and may have clinical utility for stratifying patients for personalised medicine in RA.
Topics: Humans; Arthritis, Rheumatoid; Synovial Membrane; Signal Transduction; Proteomics; Female; Phosphoproteins; Middle Aged; Male; Adult; Aged; Proteome
PubMed: 38867295
DOI: 10.1186/s13075-024-03351-4 -
Life Sciences Aug 2024This study aimed to identify hub ferroptosis-related genes (FRGs) and investigate potential therapy for RA based on FRGs.
AIMS
This study aimed to identify hub ferroptosis-related genes (FRGs) and investigate potential therapy for RA based on FRGs.
MAIN METHODS
The differentially expressed FRGs in synovial tissue of RA patients were obtained from the dataset GSE12021 (GPL96). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were conducted to investigate the potential signaling pathways associated with FRGs. Hub genes were identified through topological analysis. The expression levels of these hub genes as well as their diagnostic accuracies were further evaluated. Connectivity Map (CMap) database was utilized to analyze the top 10 FRGs-guided potential drugs for RA. In vitro and in vivo experiments were carried out for further validation.
KEY FINDINGS
2 hub genes among 58 FRGs were identified (EGR1 and CDKN1A), and both were down regulated in RA synovial tissue. GPx4 expression was also decreased in the RA synovial tissue. The natural compound withaferin-a exhibited the highest negative CMap score. In-vitro and in-vivo experiments demonstrated anti-arthritic effects of withaferin-a.
SIGNIFICANCE
Ferroptosis participates in pathogenesis of RA, ferroptosis-related genes EGR1 and CDKN1A can be used as diagnostic and therapeutic targets for RA. Withaferin-a can be used as potential anti-arthritic treatment.
Topics: Ferroptosis; Arthritis, Rheumatoid; Humans; Animals; Mice; Synovial Membrane; Male
PubMed: 38866217
DOI: 10.1016/j.lfs.2024.122780 -
Nature Communications Jun 2024Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired...
Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function. CD8 + T cells show higher oligoclonality than CD4 + T cells, with the largest synovial clones enriched in GZMK+ cells. CD8 + T cells with possibly virus-reactive TCRs are distributed across transcriptomic clusters. In the B cell compartment, NR4A1+ activated B cells, and plasma cells are enriched in the synovium and demonstrate substantial clonal expansion. We identify synovial plasma cells that share BCRs with synovial ABC, memory, and activated B cells. Receptor-ligand analysis predicted IFNG and TNFRSF members as mediators of synovial Tph-B cell interactions. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate the synovium of patients with RA.
Topics: Humans; Arthritis, Rheumatoid; Synovial Membrane; B-Lymphocytes; Female; Male; Middle Aged; CD8-Positive T-Lymphocytes; Lymphocyte Subsets; CD4-Positive T-Lymphocytes; Single-Cell Analysis; Transcriptome; Plasma Cells; Aged; Lymphocyte Activation; Adult
PubMed: 38862501
DOI: 10.1038/s41467-024-49186-0 -
RMD Open Jun 2024To assess the presence and anatomical distribution of activated fibroblasts in the joints and entheses of patients with psoriasis with arthralgia and to test how...
OBJECTIVES
To assess the presence and anatomical distribution of activated fibroblasts in the joints and entheses of patients with psoriasis with arthralgia and to test how fibroblast activation visualised by gallium-labelled fibroblast activation protein inhibitor-04 (Ga-FAPI-04)-positron emission tomography (PET)/CT correlates with clinical tenderness, musculoskeletal ultrasound findings and progression to psoriatic arthritis (PsA).
METHODS
We conducted a prospective cohort study in patients with psoriasis and arthralgia who underwent clinical and ultrasound evaluation and whole-body PET/CT imaging with Ga-FAPI-04. Ga-FAPI-04 uptake at synovial and entheseal sites was assessed by maximal standardised uptake values (SUVmax) and PET/CT Joint Index (JI); logistic regression models were used to investigate its correlation with clinical and ultrasound findings. Survival analyses were performed on patients with at least 6 months of follow-up.
RESULTS
36 patients with psoriasis were enrolled. Ga-FAPI-04 uptake was found in 318 (7.9%) joints and 369 (7.3%) entheses in 29 (80.6%) participants, with a mean SUVmax (SD) of 3.2 (1.8) for joints and 2.9 (1.6) for entheses. Large joints and the lower limbs were predominantly affected. A significant positive relationship was found between Ga-FAPI-04-PET/CT signal intensity and the 68 tender joint count (SUVmax: p<0.001; PET/CT-JI: p<0.001) and tender entheses count (SUVmax: p<0.001; PET/CT-JI: p=0.002). No correlations were found with ultrasound findings (SUVmax: p=0.969; PET/CT-JI: p=0.720). Patients with relevant synovio-entheseal Ga-FAPI-04 uptake showed a statistically significant higher risk of developing PsA (p=0.02), independent of ultrasound findings.
CONCLUSIONS
Patients with psoriasis presenting with arthralgia show localised signs of resident tissue activation in joints and entheses, which are associated with higher risk of developing PsA.
Topics: Humans; Arthritis, Psoriatic; Male; Female; Middle Aged; Positron Emission Tomography Computed Tomography; Psoriasis; Adult; Prospective Studies; Fibroblasts; Synovial Membrane; Aged; Ultrasonography; Disease Progression
PubMed: 38862244
DOI: 10.1136/rmdopen-2024-004294 -
Cureus May 2024Chronic unreduced dislocations of the proximal interphalangeal joint are uncommon, and management principles for these injuries have not been defined. The dislocation...
Chronic unreduced dislocations of the proximal interphalangeal joint are uncommon, and management principles for these injuries have not been defined. The dislocation can be volar or dorsal and closed reduction is rarely successful owing to soft tissue contractures. Treatment options in literature reviews for such rare injuries included open reduction of pip joint with volar plate arthroplasty, extension block pinning, hemi hamate arthroplasty, pip joint arthrodesis, Suzuki dynamic frame fixation, open reduction and repair of capsule and collateral ligaments with suture anchors. Few cases of amputation following treatment were even reported in literature emphasizing the role of meticulous soft tissue handling in such neglected cases of hand. We report six cases of neglected (more than three months old) dorsal dislocation of the PIP joint of the hand, treated with volar plate arthroplasty and extension block pinning. A functional range of motion with a stable joint can be achieved in such injuries with volar plate arthroplasty, as long as the articular cartilage is relatively preserved and bone loss is <30%.
PubMed: 38860079
DOI: 10.7759/cureus.60077 -
Nature Reviews. Rheumatology Jul 2024Joint kinematic instability, arising from congenital or acquired musculoskeletal pathoanatomy or from imbalances in anabolism and catabolism induced by... (Review)
Review
Joint kinematic instability, arising from congenital or acquired musculoskeletal pathoanatomy or from imbalances in anabolism and catabolism induced by pathophysiological factors, leads to deterioration of the composition, structure and function of cartilage and, ultimately, progression to osteoarthritis (OA). Alongside articular cartilage degeneration, synovial fluid lubricity decreases in OA owing to a reduction in the concentration and molecular weight of hyaluronic acid and surface-active mucinous glycoproteins that form a lubricating film over the articulating joint surfaces. Minimizing friction between articulating joint surfaces by lubrication is fundamental for decreasing hyaline cartilage wear and for maintaining the function of synovial joints. Augmentation with highly viscous supplements (that is, viscosupplementation) offers one approach to re-establishing the rheological and tribological properties of synovial fluid in OA. However, this approach has varied clinical outcomes owing to limited intra-articular residence time and ineffective mechanisms of chondroprotection. This Review discusses normal hyaline cartilage function and lubrication and examines the advantages and disadvantages of various strategies for restoring normal joint lubrication. These strategies include contemporary viscosupplements that contain antioxidants, anti-inflammatory drugs or platelet-rich plasma and new synthetic synovial fluid additives and cartilage matrix enhancers. Advanced biomimetic tribosupplements offer promise for mitigating cartilage wear, restoring joint function and, ultimately, improving patient care.
Topics: Humans; Viscosupplementation; Osteoarthritis; Hyaluronic Acid; Cartilage, Articular; Viscosupplements; Synovial Fluid; Dietary Supplements
PubMed: 38858605
DOI: 10.1038/s41584-024-01125-5 -
JPRAS Open Jun 2024A synovial cyst is a herniation of synovial tissue through a joint capsule, often mistaken for a ganglion cyst. The key distinctions are that synovial cysts have a...
BACKGROUND
A synovial cyst is a herniation of synovial tissue through a joint capsule, often mistaken for a ganglion cyst. The key distinctions are that synovial cysts have a synovial cell lining, while a ganglion cyst is delineated by dense fibrous connective tissue. Typically found near joints, synovial cysts are associated with conditions like osteoarthritis, prevalent in females aged 20 to 50. We present a rare case of a synovial cyst in the extensor digitorum superficialis of the right hand.
CASE SUMMARY
A 53-year-old Hispanic female visited our hand clinic due to a 3-year history of pain on the back of her right hand. At exploration, a 3 × 3 cm soft tumor was identified. Surgery revealed a clear-yellowish mass within the extensor digitorum superficialis tendon. Following the surgery, synovial cyst was confirmed by pathology and the patient was discharged without complications.
CONCLUSION
This case highlights the rare presentation of an intratendinous synovial cyst and emphasizes the importance of a comprehensive understanding of synovial cysts in the differential diagnosis of hand tumors.
PubMed: 38854624
DOI: 10.1016/j.jpra.2024.02.014 -
Journal of Hand and Microsurgery Mar 2024The standard treatment for mucous cysts with Heberden nodes is excision of the dorsolateral osteophytes and capsule of the distal interphalangeal joint or thumb...
The standard treatment for mucous cysts with Heberden nodes is excision of the dorsolateral osteophytes and capsule of the distal interphalangeal joint or thumb interphalangeal joint, including the stalk of the cyst. The skin incision varies for cases depending upon the geometry. We propose a surgical method utilizing blind lateral approaches for treating such mucous cysts.
PubMed: 38854384
DOI: 10.1055/s-0043-1761228