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Journal of Orthopaedic Case Reports Jun 2024Alkaptonuria is a rare autosomal recessive genetic disorder found in 2-5/million live births. It results in dark brown pigmentation of connective tissues including...
INTRODUCTION
Alkaptonuria is a rare autosomal recessive genetic disorder found in 2-5/million live births. It results in dark brown pigmentation of connective tissues including cartilage and joint capsule that can often lead to arthropathy of large joints. However, bone fractures are unusual. This article describes a fracture neck of the femur in a patient with undiagnosed alkaptonuria managed at a rural center.
CASE REPORT
A 60-year-old daily wage laborer with previously pain-free hips presented with sudden onset pain in the left hip while walking with no prior history of trauma. Radiographs showed a displaced fracture of the neck of the left femur. She underwent Left hip hemiarthroplasty. Intraoperatively, her soft-tissue including the joint capsule and the femoral head had dark brown pigmentation. Postoperatively, her urine was tested and the same turned black supporting the clinical diagnosis of alkaptonuria. At her 1-year follow-up, she had a painless, stable, and mobile hip.
CONCLUSION
We report a rare and unique case of neck of femur fracture in a patient with alkaptonuria treated with hemiarthroplasty in a resource-limited hospital in rural India. It is essential to consider the possibility of this condition when we come across a patient with an atypical fracture presentation. This article also presents an overview of alkaptonuria with a discussion on etiopathogenesis, clinical presentation, diagnosis, and management.
PubMed: 38910974
DOI: 10.13107/jocr.2024.v14.i06.4508 -
JBJS Essential Surgical Techniques 2024A number of techniques have been described to enter the capsule and gain access to the hip joint during hip arthroscopy. Among these, the interportal and T-capsulotomies...
BACKGROUND
A number of techniques have been described to enter the capsule and gain access to the hip joint during hip arthroscopy. Among these, the interportal and T-capsulotomies are the most commonly utilized; however, these approaches transect the iliofemoral ligament, which normally resists anterior subluxation and stabilizes extension. Thus, these approaches may introduce capsuloligamentous instability and have been associated with complications such as dislocation, postoperative pain, microinstability, seroma, and heterotopic ossification. Although prior literature has demonstrated durable mid-term results for patients undergoing capsulotomies with capsular closure, avoidance of iatrogenic injury to the hip capsule altogether is preferable. Thus, the puncture capsulotomy technique we present is minimally invasive, preserves the biomechanics of the hip joint and capsule without disrupting the iliofemoral ligament, and allows for appropriate visualization of the joint through placement of multiple small portals.
DESCRIPTION
Following induction of anesthesia and with the patient supine on a hip traction table, the nonoperative leg is positioned at 45° abduction with support of a well-padded perineal post, and the operative hip is placed into valgus against the post. Intra-articular fluid distention with normal saline solution is utilized to achieve approximately 9 mm of inferior migration of the femoral head and decrease risk of iatrogenic nerve injury. Then, under fluoroscopic guidance, an anterolateral portal is created 1 cm anterior and 1 cm superior to the greater trochanter at an approximately 15° to 20° angle. Second, via arthroscopic visualization, the anterior portal is created 1 cm distal and 1 cm lateral to the intersection of a vertical line drawn at the anterior superior iliac spine and a horizontal line at the level of the anterolateral portal. Third, equidistant between the anterior and anterolateral portals, the mid-anterior portal is created distally. Finally, at one-third of the distance between the anterior superior iliac spine and the anterolateral portal, the Dienst portal is created. Thus, these 4 portals form a quadrilateral arrangement through which puncture capsulotomy can be performed.
ALTERNATIVES
Alternative approaches to the hip capsule include interportal and T-capsulotomies, with or without capsular closure. Although the most frequently utilized, these approaches transect the iliofemoral ligament and thus may introduce capsuloligamentous instability.
RATIONALE
The puncture capsulotomy technique has the advantage of maintaining the integrity of the capsule through the placement of 4 small portals. The technique does not transect the iliofemoral ligament and thus does not introduce capsuloligamentous instability. Furthermore, although good mid-term outcomes have been reported with capsular closure, the present technique avoids creating unnecessary injury to the capsule and complications of an unrepaired capsule or, conversely, of plication.
EXPECTED OUTCOMES
Patients who underwent the puncture capsulotomy technique showed significant improvements in multiple functional outcome scores at a mean follow-up of 30.4 months, including the International Hip Outcome Tool (iHOT-33) (39.6 preoperatively to 76.1 postoperatively), Hip Outcome Score-Activities of Daily Living subscale (HOS-ADL) (70.0 to 89.3), HOS Sport-Specific Subscale (HOS-SSS) (41.8 to 75.7), and modified Harris hip score (mHHS) (60.1 to 84.9). At 2 years postoperatively with respect to iHOT-33, 81.0% of patients achieved the minimal clinically important difference, 62.0% achieved the patient acceptable symptom state, and 58.9% achieved substantial clinical benefit. In addition, mean visual analog scale pain scores improved significantly over the follow-up period (6.3 to 2.2; p < 0.001). Finally, there were zero occurrences of infection, osteonecrosis of the femoral head, dislocation or instability, or femoral neck fracture in patients treated with puncture capsulotomy.
IMPORTANT TIPS
Anterolateral portal placement should be performed using the intra-articular fluid distention technique with fluoroscopy to avoid risk of iatrogenic labral damage and distraction-induced neurapraxia. Subsequent portals must then be placed under direct arthroscopic visualization.On establishment of the anterolateral portal, the scope should be switched to the anterior portal to ensure that the anterolateral portal has not been placed through the labrum and to adjust its placement to better access pathology. This portal, as well as all others, may be subsequently modified by adjusting the angle of the cannula, without making a new skin incision.If a cam lesion is located more anteromedially or posterolaterally, an additional accessory portal may be made distal or proximal to the anterolateral portal, respectively, in order to enhance visualization.Intermittent traction is utilized throughout the surgery. No traction is utilized during preparing and draping, suture tensioning and tie-down, and femoroplasty, with minimal traction during acetabuloplasty; these precautions serve to prevent iatrogenic superficial peroneal nerve injury.There can be a steep learning curve for this technique. In particular, greater surgical experience is required to perform adequate femoral osteoplasty for large cam lesions with this approach.Instrument maneuverability and visualization can be somewhat constrained with this approach.It is more difficult to perform certain procedures with this technique, including segmental and circumferential labral reconstructions, particularly with remote grafts.
ACRONYMS AND ABBREVIATIONS
iHOT-33 = International Hip Outcome Tool-33HOS-ADL = Hip Outcome Score-Activities of Daily Living subscaleHOS-SSS = Hip Outcome Score-Sport-Specific SubscaleAP = anteroposteriorMRA = magnetic resonance arthrogramMRI = magnetic resonance imagingCT = computed tomographyASIS = anterior superior iliac spinemHHS = modified Harris hip score.
PubMed: 38903605
DOI: 10.2106/JBJS.ST.23.00061 -
BMC Immunology Jun 2024Rheumatoid arthritis (RA) is a chronic immune system disease with a high disability rate threatening the living quality of patients. Identifying potential biomarkers for...
BACKGROUND
Rheumatoid arthritis (RA) is a chronic immune system disease with a high disability rate threatening the living quality of patients. Identifying potential biomarkers for RA is of necessity to improve the prevention and management of RA.
OBJECTIVES
This study focused on miR-146b-3p evaluating its clinical significance and revealing the underlying regulatory mechanisms.
MATERIALS AND METHODS
A total of 107 RA patients were enrolled, and both serum and synovial tissues were collected. Another 78 osteoarthritis patients (OA, providing synovial tissues), and 72 healthy individuals (providing serum samples) were enrolled as the control group. The expression of miR-146b-3p was analyzed by PCR and analyzed with ROC and Pearson correlation analyses evaluating its significance in diagnosis and development prediction of RA patients. In vitro, MH7A cells were treated with TNF-α. The regulation of cell proliferation, motility, and inflammation by miR-146b-3p was assessed by CCK8, Transwell, and ELISA assays.
RESULTS
Significant upregulation of miR-146b-3p was observed in serum and synovial tissues of RA patients, which distinguished RA patients and were positively correlated with the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), anti-cyclic citrullinated peptide antibodies (anti-CCP), and rheumatoid factor (RF) of RA patients. TNF-α promoted the proliferation and motility of MH7A cells and induced significant inflammation in cells. Silencing miR-146b-3p alleviated the effect of TNF-α and negatively regulated the expression of HMGCR. The knockdown of HMGCR reversed the protective effect of miR-146b-3p silencing on TNF-α-stimulated MH7A cells.
CONCLUSIONS
Increased miR-146b-3p served as a biomarker for the diagnosis and severity of RA. Silencing miR-146b-3p could suppress TNF-α-induced excessive proliferation, motility, and inflammation via regulating HMGCR in MH7A cells.
Topics: Arthritis, Rheumatoid; Humans; MicroRNAs; Cell Proliferation; Cell Movement; Tumor Necrosis Factor-alpha; Male; Middle Aged; Female; Cell Line; Up-Regulation; Biomarkers; Inflammation; Synovial Membrane; Adult; Aged
PubMed: 38902605
DOI: 10.1186/s12865-024-00629-9 -
The New Zealand Medical Journal Jun 2024To quantify and characterise patients with coexistent septic arthritis (SA) and crystal arthritis (CA) (SACA) in an emergency department (ED) setting. (Observational Study)
Observational Study
AIM
To quantify and characterise patients with coexistent septic arthritis (SA) and crystal arthritis (CA) (SACA) in an emergency department (ED) setting.
METHODS
A single-centre, retrospective, 10-year observational study was conducted at a major referral centre. Patients with a positive joint aspirate for CA or SA carried out in ED, were included. The Newman criteria were utilised to define SA.
RESULTS
Of the 567 patients included in the final analysis, 427 had CA and 140 had a final diagnosis of SA. Twenty-three point six percent of patients diagnosed with SA had concomitant CA, while 7.2% of patients diagnosed with CA had concomitant SA. The greatest predisposing factors for SACA were previous history of gout, rheumatoid arthritis, being immunocompromised or having joint metalware. Synovial fluid (SF) white cell count (WCC) showed excellent predictive capability for joint infection with the area under the receiver operating characteristic curves (AUROCs) of 0.81 and 0.87 for SA and SACA respectively. The receiver operating characteristic curves (ROCs) reported a SF WCC cutoff of 32,000/mm3 allowed for 100% sensitivity and approximately 50% specificity.
CONCLUSIONS
SACA remains a small but important sub-group of patients at risk of misdiagnosis of CA alone. SF WCC of 32,000/mm3 may be a better cutoff than the traditionally accepted 50,000/mm3, possibly warranting inpatient admission for investigation and management of presumed SA.
Topics: Humans; Arthritis, Infectious; Retrospective Studies; Male; Female; New Zealand; Aged; Middle Aged; Crystal Arthropathies; Synovial Fluid; Emergency Service, Hospital; Aged, 80 and over; Risk Factors; Adult; Leukocyte Count; Gout
PubMed: 38901050
DOI: 10.26635/6965.6510 -
Frontiers in Immunology 2024Osteoarthritis (OA) is the most common form of arthritis, characterized by osteophyte formation, cartilage degradation, and structural and cellular alterations of the... (Review)
Review
Osteoarthritis (OA) is the most common form of arthritis, characterized by osteophyte formation, cartilage degradation, and structural and cellular alterations of the synovial membrane. Activated fibroblast-like synoviocytes (FLS) of the synovial membrane have been identified as key drivers, secreting humoral mediators that maintain inflammatory processes, proteases that cause cartilage and bone destruction, and factors that drive fibrotic processes. In normal tissue repair, fibrotic processes are terminated after the damage has been repaired. In fibrosis, tissue remodeling and wound healing are exaggerated and prolonged. Various stressors, including aging, joint instability, and inflammation, lead to structural damage of the joint and micro lesions within the synovial tissue. One result is the reduced production of synovial fluid (lubricants), which reduces the lubricity of the cartilage areas, leading to cartilage damage. In the synovial tissue, a wound-healing cascade is initiated by activating macrophages, Th2 cells, and FLS. The latter can be divided into two major populations. The destructive thymocyte differentiation antigen (THY)1 phenotype is restricted to the synovial lining layer. In contrast, the THY1 phenotype of the sublining layer is classified as an invasive one with immune effector function driving synovitis. The exact mechanisms involved in the transition of fibroblasts into a myofibroblast-like phenotype that drives fibrosis remain unclear. The review provides an overview of the phenotypes and spatial distribution of FLS in the synovial membrane of OA, describes the mechanisms of fibroblast into myofibroblast activation, and the metabolic alterations of myofibroblast-like cells.
Topics: Humans; Osteoarthritis; Fibroblasts; Animals; Phenotype; Fibrosis; Synoviocytes; Synovial Membrane
PubMed: 38895122
DOI: 10.3389/fimmu.2024.1385006 -
Cells May 2024Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterised by the formation of a hyperplastic pannus, as well as cartilage and bone damage. The... (Review)
Review
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterised by the formation of a hyperplastic pannus, as well as cartilage and bone damage. The pathogenesis of RA is complex and involves broad interactions between various cells present in the inflamed synovium, including fibroblast-like synoviocytes (FLSs), macrophages, and T cells, among others. Under inflammatory conditions, these cells are activated, further enhancing inflammatory responses and angiogenesis and promoting bone and cartilage degradation. Novel treatment methods for RA are greatly needed, and mesenchymal stromal cells (MSCs) have been suggested as a promising new regenerative and immunomodulatory treatment. In this paper, we present the interactions between MSCs and RA-FLSs, and macrophages and T cells, and summarise studies examining the use of MSCs in preclinical and clinical RA studies.
Topics: Humans; Arthritis, Rheumatoid; Mesenchymal Stem Cells; Mesenchymal Stem Cell Transplantation; Animals; Macrophages; T-Lymphocytes; Synovial Membrane; Synoviocytes
PubMed: 38891047
DOI: 10.3390/cells13110915 -
European Journal of Radiology Open Jun 2024The present study aimed to compare the computed tomography (CT) and magnetic resonance imaging (MRI) features of solid pseudopapillary neoplasms (SPNs) and pancreatic...
PURPOSE
The present study aimed to compare the computed tomography (CT) and magnetic resonance imaging (MRI) features of solid pseudopapillary neoplasms (SPNs) and pancreatic neuroendocrine neoplasms (pNENs).
METHOD
Lesion imaging features of 39 patients with SPNs and 127 patients with pNENs were retrospectively extracted from 104 CT and 91 MRI scans.
RESULTS
Compared to pNEN patients, SPN patients were significantly younger (mean age 51.8 yrs versus 32.7 yrs) and more often female (female: male ratio, 5.50:1 versus 1.19:1). Most SPNs and pNENs presented as well-defined lesions with an expansive growth pattern. SPNs more often appeared as round or ovoid lesions, compared to pNENs which showed a lobulated or irregular shape in more than half of cases (p<0.01). A surrounding capsule was detected in the majority of SPNs, but only in a minority of pNENs (<0.01). Hemorrhage occurred non-significantly more often in SPNs (p=0.09). Signal inhomogeneity in T1-fat-saturated (p<0.01) and T2-weighted imaging (p=0.046) as well as cystic degeneration (p<0.01) were more often observed in SPNs. Hyperenhancement in the arterial and portal-venous phase was more common in pNENs (p<0.01). Enlargement of locoregional lymph nodes (p<0.01) and liver metastases (p=0.03) were observed in some pNEN patients, but not in SPN patients. Multivariate logistic regression identified the presence of a capsule (p<0.01), absence of arterial hyperenhancement (p<0.01), and low patient age (p<0.01), as independent predictors for SPN.
CONCLUSIONS
The present study provides three key features for differentiating SPNs from pNENs extracted from a large patient cohort: presence of a capsule, absence of arterial hyperenhancement, and low patient age.
PubMed: 38882634
DOI: 10.1016/j.ejro.2024.100576 -
Experimental Biology and Medicine... 2024Rheumatoid fibroblast-like synoviocytes (RFLS) have an important role in the inflammatory pathogenesis of rheumatoid arthritis (RA). Toll-like receptor 3 (TLR3) is...
Rheumatoid fibroblast-like synoviocytes (RFLS) have an important role in the inflammatory pathogenesis of rheumatoid arthritis (RA). Toll-like receptor 3 (TLR3) is upregulated in RFLS; its activation leads to the production of interferon-β (IFN-β), a type I IFN. IFN-stimulated gene 56 (ISG56) is induced by IFN and is involved in innate immune responses; however, its role in RA remains unknown. Therefore, the purpose of this study was to investigate the role of TLR3-induced ISG56 in human RFLS. RFLS were treated with polyinosinic-polycytidylic acid (poly I:C), which served as a TLR3 ligand. ISG56, melanoma differentiation-associated gene 5 (MDA5), and C-X-C motif chemokine ligand 10 (CXCL10) expression were measured using quantitative reverse transcription-polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. Using immunohistochemistry, we found that ISG56 was expressed in synovial tissues of patients with RA and osteoarthritis. Under poly I:C treatment, ISG56 was upregulated in RFLS. In addition, we found that the type I IFN-neutralizing antibody mixture suppressed ISG56 expression. ISG56 knockdown decreased CXCL10 expression and MDA5 knockdown decreased ISG56 expression. In addition, we found that ISG56 was strongly expressed in the synovial cells of patients with RA. TLR3 signaling induced ISG56 expression in RFLS and type I IFN was involved in ISG56 expression. ISG56 was also found to be associated with CXCL10 expression, suggesting that ISG56 may be involved in TLR3/type I IFN/CXCL10 axis, and play a role in RA synovial inflammation.
Topics: Humans; Toll-Like Receptor 3; Arthritis, Rheumatoid; Poly I-C; Signal Transduction; Synoviocytes; Chemokine CXCL10; Interferon-Induced Helicase, IFIH1; Cells, Cultured; Synovial Membrane; Adaptor Proteins, Vesicular Transport; RNA-Binding Proteins; Adaptor Proteins, Signal Transducing; Apoptosis Regulatory Proteins
PubMed: 38881847
DOI: 10.3389/ebm.2024.10122 -
Journal of Orthopaedic Surgery and... Jun 2024This study aimed to validate alterations in the gene expression of DNA methylation-related enzymes and global methylation in the peripheral blood mononuclear cell (PBMC)...
BACKGROUND
This study aimed to validate alterations in the gene expression of DNA methylation-related enzymes and global methylation in the peripheral blood mononuclear cell (PBMC) and synovial tissues of animal hip osteoarthritis (OA) models.
METHODS
Animals were assigned to the control (no treatment), sham (25 µL of sterile saline), and OA (25 µL of sterile saline and 2 mg of monoiodoacetate) groups. Microcomputed tomography scan, histopathological assessment and pain threshold measurement were performed after induction. The mRNA expression of the DNA methylation machinery genes and global DNA methylation in the PBMC and hip synovial tissue were evaluated.
RESULTS
The OA group presented with hip joint OA histopathologically and radiologically and decreased pain threshold. The mRNA expression of DNA methyltransferase (Dnmt 3a), ten-eleven translocation (Tet) 1 and Tet 3 in the synovial tissue of the OA group was significantly upregulated. Global DNA methylation in the synovial tissue of the OA group was significantly higher than that of the control and sham groups.
CONCLUSIONS
The intra-articular administration of monoiodoacetate induced hip joint OA and decreased pain threshold. The DNA methylation machinery in the synovial tissues of hip OA was altered.
Topics: DNA Methylation; Animals; Osteoarthritis, Hip; Disease Models, Animal; Male; Rats; Iodoacetic Acid; Synovial Membrane; Leukocytes, Mononuclear; Rats, Sprague-Dawley; DNA Methyltransferase 3A; Pain Threshold
PubMed: 38880910
DOI: 10.1186/s13018-024-04847-0 -
Medical Science Monitor : International... Jun 2024BACKGROUND Osteoarthritis (OA) is a chronic degenerative disease characterized by synovitis and has been implicated in sphingolipid metabolism disorder. However, the...
BACKGROUND Osteoarthritis (OA) is a chronic degenerative disease characterized by synovitis and has been implicated in sphingolipid metabolism disorder. However, the role of sphingolipid metabolism pathway (SMP)-related genes in the occurrence of OA and synovial immune dysregulation remains unclear. MATERIAL AND METHODS In this study, we obtained synovium-related databases from GEO (n=40 for both healthy controls and OA) and analyzed the expression levels of SMP-related genes. Using 2 algorithms, we identified hub genes and developed a diagnostic model incorporating these hub genes to predict the occurrence of OA. Subsequently, the hub genes were further validated in peripheral blood samples from OA patients. Additionally, CIBERSORT and MCP-counter analyses were employed to explore the correlation between hub genes and immune dysregulation in OA synovium. WGCNA was used to determine enriched modules in different clusters. RESULTS Overall, the expression levels of SMP genes were upregulated in OA synovium. We identified 6 hub genes of SMP and constructed an excellent diagnostic model (AUC=0.976). The expression of re-confirmed hub genes showed associations with immune-related cell infiltration and levels of inflammatory cytokines. Furthermore, we observed heterogeneity in the expression patterns of hub genes across different clusters of OA. Notably, older patients displayed increased susceptibility to elevated levels of pain-related inflammatory cytokines and infiltration of immune cells. CONCLUSIONS The SMP-related hub genes have the potential to serve as diagnostic markers for OA patients. Moreover, the 4 hub genes of SMP demonstrate wide participation in immune dysregulation in OA synovium. The activation of different pathways is observed among different populations of patients with OA.
Topics: Humans; Synovial Membrane; Osteoarthritis; Sphingolipids; Gene Expression Profiling; Gene Regulatory Networks; Male; Female; Transcriptome; Databases, Genetic; Middle Aged; Case-Control Studies
PubMed: 38877693
DOI: 10.12659/MSM.943369