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BACKGROUND: Studies have highlighted the important role of cell division cycle associated 5 (CDCA5) in tumor-associated immune dysfunction. We studied immune dysfunction based on CDCA5 expression in lung adenocarcinoma and investigated its potential as a biomarker for patients undergoing anti-programmed death protein-1/ programmed death ligand-1 (PD-1/PD-L1) inhibitor therapy. METHODS: We used the CIBERSORTx algorithm to investigate the immune cell distribution based on CDCA5 and explored its potential as a biomarker for PD-1/PD-L1 therapy using Tumor Immune Dysfunction and Exclusion in three lung adenocarcinoma datasets. Thus, we validated the role of CDCA5 as a biomarker in patients treated with PD-1/PD-L1 inhibitors. We also investigated the pathways through which CDCA5 regulates PD-L1 expression in a cell line. RESULTS: The high CDCA5 expression group showed elevated interferon gamma signature, CD274 expression, CD8+ T cell levels, tumor mutation burden, and microsatellite instability. Higher CDCA5 expression was associated with poorer prognosis in patients not treated with PD-1/PD-L1 inhibitors. However, in patients treated with PD-1/PD-L1 inhibitors, higher CDCA5 expression correlated with better response rates and prognosis. CDCA5 expression positively correlated with inhibitory immune checkpoint molecules. CDCA5 regulated the expression of PD-L1 through the ANXA/AKT pathway, and combined suppression of CDCA5 and PD-L1 synergistically inhibited cell proliferation. CONCLUSIONS: CDCA5 served as a promising biomarker for patients undergoing PD-L1/PD-1 inhibitor treatment, and co-inhibition of CDCA5 and PD-L1 could serve as an effective therapeutic strategy.
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(1) Background: it is challenging to determine the accurate grades of cartilaginous bone tumors. Using bone single photon emission computed tomography (SPECT)/computed tomography (CT), maximum standardized uptake value (SUVmax) was found to be significantly associated with different grades of cartilaginous bone tumor. The inquiry focused on the effect of the tumor matrix on SUVmax. (2) Methods: a total of 65 patients from 2017 to 2022 with central cartilaginous bone tumors, including enchondromas and low-to-intermediate grade chondrosarcomas, who had undergone bone SPECT/CT were retrospectively enrolled. The SUVmax was recorded and any aggressive CT findings of cartilaginous bone tumor and Hounsfield units (HU) of the chondroid matrix as mean, minimum, maximum, and standard deviation (SD) were reviewed on CT scans. Pearson's correlation analysis was performed to determine the relationship between CT features and SUVmax. Subgroup analysis was also performed between the benign group (enchondroma) and the malignant group (grade 1 and 2 chondrosarcoma) for comparison of HU values and SUVmax. (3) Results: a significant negative correlation between SUVmax and HU measurements, including HUmax, HUmean, and HUSD, was found. The subgroup analysis showed significantly higher SUVmax in the malignant group, with more frequent CT aggressive features, and significantly lower HUSD in the malignant group than in the benign group. (4) Conclusions: it was observed that higher SUVmax and lower HUSD were associated with a higher probability of having a low-to-intermediate chondrosarcoma with aggressive features and a less calcified tumor matrix.
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BACKGROUND: A clear classification of the subtype and grade of soft tissue sarcoma is important for predicting prognosis and establishing treatment strategies. However, the rarity and heterogeneity of these tumors often make diagnosis difficult. In addition, it remains challenging to predict the response to chemotherapy and prognosis. Thus, we need a new method to help diagnose soft tissue sarcomas and determine treatment strategies in conjunction with traditional methods. Genetic alterations can be found in some subtypes of soft tissue sarcoma, but many other types show dysregulated gene expression attributed to epigenetic changes, such as DNA methylation status. However, research on DNA methylation profiles in soft tissue sarcoma is still insufficient to provide information to assist in diagnosis and therapeutic decisions. QUESTIONS/PURPOSES: (1) Do DNA methylation profiles differ between normal tissue and soft tissue sarcoma? (2) Do DNA methylation profiles vary between different histologic subtypes of soft tissue sarcoma? (3) Do DNA methylation profiles differ based on tumor grade? METHODS: Between January 2019 and December 2022, we treated 85 patients for soft tissue sarcomas. We considered patients whose specimens were approved for pilot research by the Human Biobank of St. Vincent's Hospital, The Catholic University of Korea, as potentially eligible. Based on this, 41% (35 patients) were eligible; 1% (one patient) was excluded because of gender mismatch between clinical and genetic data after controlling for data quality. Finally, 39 specimens (34 soft tissue sarcomas and five normal samples) were included from 34 patients who had clinical data. All tissue samples were collected intraoperatively. The five normal tissue samples were from muscle tissues. There were 20 female patients and 14 male patients, with a median age of 58 years (range 19 to 82 years). Genomic DNA was extracted from frozen tissue, and DNA methylation profiles were obtained. Genomic annotation of DNA methylation sites and hierarchical cluster analysis were performed to interpret results from DNA methylation profiling. A t-test was used to analyze different methylation probes. Benjamini-Hochberg-adjusted p value calculations were used to account for bias resulting from evaluating thousands of methylation sites. RESULTS: The most common histologic subtypes were liposarcoma (n = 10) and leiomyosarcoma (n = 9). The tumor grade was Fédération Nationale des Centres de Lutte Contre Le Cancer Grades 1, 2, and 3 in 3, 15, and 16 patients, respectively. DNA methylation profiling demonstrated differences between soft tissue sarcoma and normal tissue as 21,188 cytosine-phosphate-guanine sites. Despite the small number of samples, 72 of these sites showed an adjusted p value of < 0.000001, suggesting a low probability of statistical errors. Among the 72 sites, 70 exhibited a hypermethylation pattern in soft tissue sarcoma, with only two sites showing a hypomethylation pattern. Thirty of 34 soft tissue sarcomas were distinguished from normal samples using hierarchical cluster analysis. There was a different methylation pattern between leiomyosarcoma and liposarcoma at 7445 sites. Using the data, hierarchical clustering analysis showed that liposarcoma was distinguished from leiomyosarcoma. When we used the same approach and included other subtypes with three or more samples, only leiomyosarcoma and myxofibrosarcoma were separated from the other subtypes, while liposarcoma and alveolar soft-part sarcoma were mixed with the others. When comparing DNA methylation profiles between low-grade (Grade 1) and high-grade (Grades 2 and 3) soft tissue sarcomas, a difference in methylation pattern was observed at 144 cytosine-phosphate-guanine sites. Among these, 132 cytosine-phosphate-guanine sites exhibited hypermethylation in the high-grade group compared with the low-grade group. Hierarchical clustering analysis showed a division into two groups, with most high-grade sarcomas (28 of 31) separated from the low-grade group and few (3 out of 31) clustered together with the low-grade group. However, three high-grade soft tissue sarcomas were grouped with the Grade 1 cluster, and all of these sarcomas were Grade 2. When comparing Grades 1 and 2 to Grade 3, Grade 3 tumors were separated from Grades 1 and 2. CONCLUSION: We observed a different DNA methylation pattern between soft tissue sarcomas and normal tissues. Liposarcoma was distinguished from leiomyosarcoma using methylation profiling. High-grade soft tissue sarcoma samples showed a hypermethylation pattern compared with low-grade ones. Our findings indicate the need for research using methylation profiling to better understand the diverse biological characteristics of soft tissue sarcoma. Such research should include studies with sufficient samples and a variety of subtypes, as well as analyses of the expression and function of related genes. Additionally, efforts to link this research with clinical data related to treatment and prognosis are necessary. LEVEL OF EVIDENCE: Level III, diagnostic study.
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Epithelioid angiosarcoma is a rare variant of angiosarcoma characterized by an epithelioid morphology that mimics carcinoma. Therefore, multicentric epithelioid angiosarcoma is easily misdiagnosed as bone metastasis from carcinoma and has an aggressive clinical course. Here, we present a rare case of a 61-year-old male with multicentric epithelioid angiosarcoma of the bone. Plain radiography, CT, and MRI revealed multiple osteolytic lesions in both femurs; some lesions showed soft tissue extension with cortical bone destruction. Interestingly, PET-CT revealed that the lesions were only distributed along the bones of the lower extremities, including the pelvic bones, femurs, and tibiae. Despite histological analysis initially suggesting metastatic carcinoma, after additional immunohistological staining, including that for vascular markers (CD31 and ERG), the final diagnosis was epithelioid angiosarcoma. A better understanding of the clinicoradiological features of this disease may help eliminate diagnostic confusion and provide better management.
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Tenosynovial giant cell tumor (TSGCT) is a rare soft tissue tumor that involves the synovial lining of joints, bursae, and tendon sheaths, primarily affecting young patients (usually in the fourth decade of life). The tumor comprises two subtypes: the localized type (L-TSGCT) and the diffuse type (D-TSGCT). Although these subtypes share histological and genetic similarities, they present a different prognosis. D-TSGCT tends to exhibit local aggressiveness and a higher recurrence rate compared to L-TSGCT. Magnetic resonance imaging (MRI) is the preferred diagnostic tool for both the initial diagnosis and for treatment planning. When interpreting the initial MRI of a suspected TSGCT, it is essential to consider: (i) the characteristic findings of TSGCT-evident as low to intermediate signal intensity on both T1- and T2-weighted images, with a blooming artifact on gradient-echo sequences due to hemosiderin deposition; (ii) the possibility of D-TSGCT-extensive involvement of the synovial membrane with infiltrative margin; and (iii) the resectability and extent-if resectable, synovectomy is performed; if not, a novel systemic therapy involving colony-stimulating factor 1 receptor inhibitors is administered. In the interpretation of follow-up MRIs of D-TSGCTs after treatment, it is crucial to consider both tumor recurrence and potential complications such as osteoarthritis after surgery as well as the treatment response after systemic treatment. Given its prevalence in young adult patents and significant impact on patients' quality of life, clinical trials exploring new agents targeting D-TSGCT are currently underway. Consequently, understanding the characteristic MRI findings of D-TSGCT before and after treatment is imperative.
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BACKGROUND: Acute kidney injury (AKI) has a complex pathophysiology and imposes serious health concerns worldwide. Extracellular vesicles (EVs) derived from induced mesenchymal stem cells (iMSCs) have been recognized as novel cell-free therapeutics for various inflammatory and degenerative disorders. In this study, we investigated whether iMSCs stimulated with a pan-peroxisome proliferator-activated receptor (PPAR) agonist could enhance the therapeutic efficacy of EVs against AKI. METHODS: Human iMSCs were primed with or without lanifibranor, a PPAR agonist for 24 h, and EVs were collected after an additional 24 h. The basic characteristics of EVs were evaluated using cryo-transmission electron microscopy imaging, immunoblot detection of EV markers, nanoparticle tracking analysis, and localization in AKI kidneys. In vitro, the potential of the EVs to promote the growth and survival of HK-2 cells undergoing cisplatin-induced apoptosis and anti-inflammatory effects in M1-polarized THP-1 was compared. Subsequently, AKI was induced in BALB/c mice using cisplatin. After 8 and 24 h of cisplatin treatment, iMSC-EVs or pan-PPAR-iMSC-EVs were injected intravascularly. At 96 h after cisplatin administration, the renoprotective effects of iMSC-EVs or pan-PPAR-iMSC-EVs in inhibiting inflammation and apoptosis were compared using serum biochemistry, histology, immunohistochemistry, and gene expression analysis by qPCR. RESULTS: Both EV types expressed EV markers and had typical EV morphology, and their localization in the renal tissue was confirmed. The proliferation and survival of HK-2 cells were higher in pan-PPAR-iMSC-EVs than those in iMSC-EVs. In M1-polarized THP-1 cells, the reduction in the mRNA expression of inflammatory cytokines was more significant in pan-PPAR-iMSC-EVs than that in iMSC-EVs. In the mouse model of cisplatin-induced AKI, pan-PPAR-iMSC-EVs markedly enhanced renoprotective effects compared to iMSC-EVs. Specifically, pan-PPAR-iMSC-EVs reduced tissue inflammation, immune cell infiltration, and apoptosis. Pan-PPAR-iMSC-EVs also increased renal capillary density. CONCLUSION: Priming iMSCs with a PPAR agonist significantly improved the therapeutic potential of EVs by reducing inflammation and apoptosis. The reported strategy may contribute to the development of a novel cell-free option for AKI treatment. TRIAL REGISTRATION: Not applicable.
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Injúria Renal Aguda , Vesículas Extracelulares , Receptores Ativados por Proliferador de Peroxissomo , Animais , Humanos , Camundongos , Injúria Renal Aguda/patologia , Cisplatino , Vesículas Extracelulares/metabolismo , Inflamação/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Células-Tronco Mesenquimais/metabolismoRESUMO
Recent studies have indicated that RRM2 plays a crucial part in the tumor immune microenvironment. According to the expression of RRM2, we evaluated immune cell infiltration, immunotherapy biomarkers, and the expression of immune checkpoint molecules in four lung adenocarcinoma (LUAD) datasets. We employed the Tumor Immune Dysfunction and Exclusion (TIDE) and CIBERSORTx algorithms to examine the patterns of immune cell distribution and evaluate the responses to anti-programmed death protein-1/programmed death ligand-1 (PD-1/PD-L1) therapy in three publicly available LUAD datasets. These findings were corroborated using a validation group comprising patients who received treatment with PD-1/PD-L1 inhibitors. Additionally, we conducted experiments using LUAD cell lines to investigate how RRM2 affects the expression of PD-L1. In comparison to the low RRM2 group, the high RRM2 group exhibited a high interferon gamma signature, high T-cell-inflamed signature, high CD274 expression, high CD8+ T cell levels, low cancer-associated fibroblasts, and low M2 macrophages, according to TIDE analysis in the three LUAD datasets. Analysis of the three LUAD datasets using CIBERSORTx confirmed a positive correlation between RRM2 and CD8+ T cells, and this finding was validated by immunohistochemistry in a separate validation set. In the three LUAD datasets without PD-1/PD-L1 inhibitor treatment, higher RRM2 expression was associated with a poorer prognosis. However, in the LUAD dataset treated with PD-1/PD-L1 inhibitors, higher RRM2 expression was associated with better prognosis. In the three datasets, the high-RRM2 group exhibited higher expression of inhibitory immune checkpoint molecules. In a LUAD cell line study, we discovered that RRM2 regulates PD-L1 expression through the ANXA1/AKT pathway. The expression of RRM2 shows promise as a predictive biomarker for PD-1/PD-L1 inhibitors in LUAD patients, and it may represent a new target to overcome resistance to PD-L1/PD-1 therapies.
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Synovial sarcomas are rare and highly aggressive soft-tissue sarcomas, primarily affecting adolescents and young adults aged 15-40 years. These tumors typically arise in the deep soft tissues, often near the large joints of the extremities. While the radiological features of these tumors are not definitely indicative, the presence of calcification in a soft-tissue mass (occurring in 30% of cases), adjacent to a joint, strongly suggests the diagnosis. Cross-sectional imaging characteristics play a crucial role in diagnosing synovial sarcomas. They often reveal significant characteristics such as multilobulation and pronounced heterogeneity (forming the "triple sign"), in addition to features like hemorrhage and fluid-fluid levels with septa (resulting in the "bowl of grapes" appearance). Nevertheless, the existence of non-aggressive features, such as gradual growth (with an average time to diagnosis of 2-4 years) and small size (initially measuring < 5 cm) with well-defined margins, can lead to an initial misclassification as a benign lesion. Larger size, older age, and higher tumor grade have been established as adverse predictive indicators for both local disease recurrence and the occurrence of metastasis. Recently, the prognostic importance of CT and MRI characteristics for synovial sarcomas was elucidated. These include factors like the absence of calcification, the presence of cystic components, hemorrhage, the bowl of grape sign, the triple sign, and intercompartmental extension. Wide surgical excision remains the established approach for definitive treatment. Gaining insight into and identifying the diverse range of presentations of synovial sarcomas, which correlate with the prognosis, might be helpful in achieving the optimal patient management.
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The pathogenesis of atopic dermatitis (AD) is multifactorial, including immune dysregulation and epidermal barrier defects, and a novel therapeutic modality that can simultaneously target multiple pathways is needed. We investigated the therapeutic effects of exosomes (IFN-γ-iExo) secreted from IFN-γ-primed induced pluripotent stem cell-derived mesenchymal stem cells (iMSC) in mice with Aspergillus fumigatus-induced AD. IFN-γ-iExo was epicutaneously administered to mice with AD-like skin lesions. The effects of IFN-γ-iExo treatment were investigated through clinical scores, transepidermal water loss (TEWL) measurements, and histopathology. To elucidate the therapeutic mechanism, we used an in vitro model of human keratinocyte HaCaT cells stimulated with IL-4 and IL-13 and performed extensive bioinformatics analysis of skin mRNA from mice. The expression of indoleamine 2,3-dioxygenase was higher in IFN-γ primed iMSCs than in iMSCs. In human keratinocyte HaCaT cells, treatment with IFN-γ-iExo led to decreases in the mRNA expression of thymic stromal lymphopoietin, IL-25, and IL-33 and increases in keratin 1, keratin 10, desmoglein 1, and ceramide synthase 3. IFN-γ-iExo treatment significantly improved clinical and histological outcomes in AD mice, including clinical scores, TEWL, inflammatory cell infiltration, and epidermal thickness. Bioinformatics analysis of skin mRNA from AD mice showed that IFN-γ-iExo treatment is predominantly involved in skin barrier function and T cell immune response. Treatment with IFN-γ-iExo improved the clinical and histological outcomes of AD mice, which were likely mediated by restoring proper skin barrier function and suppressing T cell-mediated immune response.
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Dermatite Atópica , Exossomos , Células-Tronco Pluripotentes Induzidas , Células-Tronco Mesenquimais , Animais , Humanos , Camundongos , Citocinas/metabolismo , Dermatite Atópica/tratamento farmacológico , Exossomos/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Inflamação/metabolismo , Interferon gama/metabolismo , Células-Tronco Mesenquimais/metabolismo , RNA Mensageiro/metabolismo , Pele/metabolismo , Água/metabolismoRESUMO
OBJECTIVE: Tenosynovial giant cell tumors (TSGCTs) of the knee differ in their clinical outcome according to disease subtypes and severity. The aim of this study was to determine the predictive MRI features related to local recurrence in TSGCT of the knee regarding disease subtypes and severity. METHODS: This retrospective study included 20 patients with pathology-proven TSGCT of the knee who underwent preoperative MRI and surgery from Jan. 2007 to Jan. 2022. The anatomical point of the lesion was determined with a knee mapping. And then MRI features related to disease subtype including nodularity (single vs. multinodular); margin (circumscribed vs. infiltrative); peripheral hypointenseity (present vs. absent); internal hypointensity reflecting hemosiderin deposition (speckled vs. granular) were assessed. Third, MRI features related to disease severity including involvement of bone, cartilage, and tendon were evaluated. MRI features for predicting local recurrence of TSGCT were tested using chi-square test and logistic regression analysis. RESULTS: Ten patients with diffuse-type TSGCT (D-TSGCT) and 10 patients with localized-type TSGCT (L-TSGCT) were included. There were six cases of local recurrence and all of them were D-TSGCT and none for L-TSGCT with statistical difference (P = 0.015). D-TSGCT that was direct risk factor for local recurrence showed more multinodular (80.0% vs. 10.0%; P = 0.007), infiltrative margin (90.0% vs. 10.0%; P = 0.002), and absent peripheral hypointensity (100.0% vs. 20.0%; P = 0.001) than L-TSGCT. Multivariate analysis showed infiltrative margin (odds ratio [OR], 81.0; P = 0.003) was independent MRI factor for D-TSGCT. Disease severity for risk of local recurrence included cartilage (66.7% vs. 7.1%; P = 0.024) and tendon (100.0% vs. 28.6%; P = 0.015) involvement compared to no local recurrence. Multivariate analysis showed tendon involvement (OR, 12.5; P = 0.042) was predictive MRI parameter for local recurrence. By combining tumor margin and tendon involvement, local recurrence was predicted sensitively on preoperative MRI (sensitivity, 100%; specificity, 50%; accuracy, 65%). CONCLUSION: D-TSGCTs was associated with local recurrence and showed multinodularity infiltrative margin, and absent peripheral hypointensity. Disease severity including cartilage and tendon involvement was associated with local recurrence. Preoperative MRI evaluation by combining disease subtypes and severity can predict local recurrence sensitively.
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Tumor de Células Gigantes de Bainha Tendinosa , Articulação do Joelho , Humanos , Estudos Retrospectivos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Tendões/diagnóstico por imagem , Imageamento por Ressonância MagnéticaRESUMO
Diffusion-weighted imaging (DWI) with an apparent diffusion coefficient (ADC) value is a relatively new magnetic resonance imaging (MRI) sequence that provides functional information on the lesion by measuring the microscopic movement of water molecules. While numerous studies have evaluated the promising role of DWI in musculoskeletal radiology, most have focused on tumorous diseases related to cellularity. This review article aims to summarize DWI-acquisition techniques, considering pitfalls such as T2 shine-through and T2 black-out, and their usefulness in interpreting musculoskeletal diseases with imaging. DWI is based on the Brownian motion of water molecules within the tissue, achieved by applying diffusion-sensitizing gradients. Regardless of the cellularity of the lesion, several pitfalls must be considered when interpreting DWI with ADC values in musculoskeletal radiology. This review discusses the application of DWI in musculoskeletal diseases, including tumor and tumor mimickers, as well as non-tumorous diseases, with a focus on lesions demonstrating T2 shine-through and T2 black-out effects. Understanding these pitfalls of DWI can provide clinically useful information, increase diagnostic accuracy, and improve patient management when added to conventional MRI in musculoskeletal diseases.
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Chondrosarcomas can be classified into various forms according to the presence or absence of a precursor lesion, location, and histological subtype. The new 2020 World Health Organization (WHO) Classification of Tumors of Soft Tissue and Bone classifies chondrogenic bone tumors as benign, intermediate (locally aggressive), or malignant, and separates atypical cartilaginous tumors (ACTs) and chondrosarcoma grade 1 (CS1) as intermediate and malignant tumors. respectively. Furthermore, the classification categorizes chondrosarcomas (including ACT) into eight subtypes: central conventional (grade 1 vs. 2-3), secondary peripheral (grade 1 vs. 2-3), periosteal, dedifferentiated, mesenchymal, and clear cell chondrosarcoma. Most chondrosarcomas are the low-grade, primary central conventional type. The rarer subtypes include clear cell, mesenchymal, and dedifferentiated chondrosarcomas. Comprehensive analysis of the characteristic imaging findings can help differentiate various forms of chondrosarcomas. However, distinguishing low-grade chondrosarcomas from enchondromas or high-grade chondrosarcomas is radiologically and histopathologically challenging, even for experienced radiologists and pathologists.
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INTRODUCTION: This study aimed to identify whether iliac vein compression syndrome(IVCS) is associated with deep vein thrombosis(DVT) after total knee arthroplasty(TKA) and whether lower lumbar degenerative changes were risk factors for IVCS. MATERIALS AND METHODS: A total of 259 consecutive patients who underwent TKA from January 2019 to March 2022 was retrospectively reviewed. Preoperative plain radiographs of lumbar spines and CT venography (CTV) for DVT diagnosis at postoperative 7 days were performed in all patients. Imaging findings of lower lumbar degenerative changes were analyzed on plain radiograph including lateral osteophytes, scoliosis, lateralolisthesis, retrolisthesis, anterolisthesis, and lower lumbar lordosis angle (LLLA). Percent compression at the left common iliac vein (LCIV) and right common iliac vein (RCIV) as well as DVT were evaluated on CTV. Moreover, IVCS was defined as greater than 50% of compression of the iliac vein on CTV. RESULTS: DVT occurred in 79 patients (30.5%) after TKA. The overall occurrence of DVT was significantly higher in patients with IVCS of LCIV (52.8%) than those without (18.8%, P < 0.001). When DVT was further subdivided, compared to non-IVCS, IVCS of LCIV was significantly associated with bilateral DVT (P < 0.001, both), especially distal DVT (P < 0.001, both), and IVCS of RCIV was significantly associated with right-side DVT (P = 0.031), especially popliteal (P = 0.008) and distal DVT(P = 0.011). Female patients (OR: 3.945, P = 0.039), presence of left osteophyte (OR: 2.348, P = 0.006), and higher LLLA (OR: 1.082, P < 0.001) were significantly associated with IVCS of LCIV, and presence of right osteophyte (OR: 3.494, P = 0.017) was significantly associated with IVCS of RCIV. CONCLUSION: IVCS was significantly associated with DVT after TKA and lumbar degenerative changes with lateral osteophytes and hyperlordosis were significant risk factors for IVCS.
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Artroplastia do Joelho , Síndrome de May-Thurner , Osteófito , Trombose Venosa , Humanos , Feminino , Síndrome de May-Thurner/complicações , Síndrome de May-Thurner/diagnóstico por imagem , Artroplastia do Joelho/efeitos adversos , Estudos Retrospectivos , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologiaRESUMO
RATIONALE AND OBJECTIVES: To propose a magnetic resonance imaging (MRI) prediction model for diffuse-type tenosynovial giant cell tumors (D-TSGCTs). MATERIALS AND METHODS: Anatomic locations were classified and then nodularity, margin, peripheral and internal hypointensity, and bone and cartilage involvement were evaluated on MRI. Student's t-test, chi-square test, diagnostic performance, logistic regression analysis, and decision tree were performed. RESULTS: Nineteen intra-articular (11 localized; eight diffuse) and 55 extra-articular (44 localized; 11 diffuse) TSGCTs were included. Extra-articular D-TSGCTs showed significantly more frequent multinodular (72.7% vs. 25.0%, p = 0.009), and infiltrative lesions (90.9% vs. 34.1%, p = 0.002), without peripheral hypointensity (90.9% vs. 18.2%, p < 0.001), and contained granular internal hypointensity (72.7% vs. 31.8%; p = 0.003) with more frequent bone (81.8% vs. 27.3%; p = 0.003) and cartilage (50.0% vs. 0.0%; p = 0.038) involvement than localized-type. Intra-articular D-TSGCT also showed significance in all MRI features (100.0% vs. 9.1%, p = 0.001; 100.0% vs. 27.3%, p = 0.007; 100.0% vs. 36.4%, p = 0.018; 100.0% vs. 27.3%, p = 0.007; 50.0% vs. 0.0%, p = 0.038), except bone involvement (37.5% vs. 9.1%, p = 0.352) than localized-type. Cartilage involvement revealed the highest specificity (88.6-100.0%), regardless of location. Nodularity (100.0%; odds-ratio [OR]: 70.000) and peripheral hypointensity (90.9%; OR: 62.250) demonstrated the highest sensitivities ORs for D-TSGCT in intra-articular and extra-articular cases, respectively. MRI models for D-TSGCG beginning with the cartilage involvement in both anatomic locations and next on nodularity and peripheral hypointensity in intra-articular and extra-articular locations, respectively, exhibited sensitivity and specificity of 100% and 90.9% for intra-articular and 100% and 77.2% for extra-articular TSGCTs, respectively. CONCLUSION: MRI can suggest the risk of D-TSGCT by combining imaging features with anatomic locations.
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OBJECTIVES: To determine the diagnostic values of deep changes beyond the subchondral bone in osteonecrosis of the femoral head (ONFH) to distinguish between Association Research Circulation Osseous (ARCO) stages 2 and 3A. METHODS: This retrospective study included 124 hips with ONFH of stages 2 (n = 49; 23 females; mean age, 50.7 years) and 3A (n = 75; 20 females; mean age, 53.2 years) from May 2017 to August 2022, who underwent CT (n = 124) and MRI (n = 85). Deep changes beyond subchondral bone were analyzed on CT (bone resorption area and cystic change) and on MRI (bone marrow edema [BME] and joint effusion). Diagnostic performance and multivariate analysis were evaluated for detecting stage 3A. RESULTS: Stage 3A showed more frequent bone resorption area (72.0% vs. 4.1%), cystic change (52.0% vs. 0.0%), BME (93.5% vs. 43.6%), and joint effusion (76.0% vs. 24.5%) than stage 2 (p < 0.001, all). Bone resorption area and cystic change showed low sensitivities (52.0~72.0%) but high specificities (96.0~100.0%), while BME and joint effusion showed high sensitivities (76.0~93.0%) but low specificities (56.0~76.0%) for stage 3A. Predictors were in the order of bone resorption area, cystic change, and joint effusion (odds ratio: 32.952, 26.281, 9.603, respectively), and combined bone resorption area and cystic change had the best predictive value (AUC, 0.900) for stage 3A. CONCLUSIONS: Among deep changes, bone resorption area and cystic changes were highly specific and BME and joint effusion were highly sensitive for stage 3A. Combined bone resorption area and cystic change had the best predictive value for predicting ARCO stage 3A. KEY POINTS: ⢠The exact classification between ARCO stage 2 and 3A is essential but it is sometimes difficult to distinguish between ARCO stage 2 and 3A only by subchondral fracture, especially early post-collapse stage with preservation of femoral head contour. ⢠The predictors of stage 3A were in the order of bone resorption area, cystic change, and joint effusion and combined bone resorption area and cystic change had the best predictive value for predicting stage 3A. ⢠Analysis of deep changes beyond the subchondral bone may make it easier to distinguish between ARCO stage 2 and 3A.
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Doenças da Medula Óssea , Reabsorção Óssea , Necrose da Cabeça do Fêmur , Feminino , Humanos , Pessoa de Meia-Idade , Cabeça do Fêmur/diagnóstico por imagem , Estudos Retrospectivos , Necrose da Cabeça do Fêmur/diagnóstico por imagem , Imageamento por Ressonância Magnética , Edema , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To compare the MRI findings between the localized- and diffuse-type tenosynovial giant cell tumors (TSGCTs) of digits with pathology correlation. METHODS: Twenty-eight patients with newly diagnosed TSGCTs of digits (22 localized and 6 diffuse types) who underwent preoperative MRI and surgical excision were included from Jan. 2015 to September 2021. MRI findings regarding nodularity, margins, morphology of hypointensity with pathology correlation, and disease extent (bone erosion, articular involvement, muscle involvement, tendon destruction, and neurovascular encasement) were assessed. RESULTS: Diffuse type was significantly larger (P = 0.006), more multinodular on both MRI and pathology (P = 0.038, both) with significant agreement, and infiltrative on both MRI and pathology (P < 0.001, both) with substantial agreement, and showed central granular on MRI and strong hemosiderin deposition on pathology (P = 0.022 and P = 0.021) with moderate agreement than localized type. Localized type showed significantly more frequent peripheral capsules on both MRI and pathology (P < 0.001, both) with moderate agreement than diffuse type. However, the septum on both MRI and pathology showed no statistically significant difference between the two groups (P = 0.529 and P = 0.372) without significant agreement. The disease extent was more severe in the diffuse type than the localized type regarding articular involvement (P < 0.001), muscle involvement (P < 0.001), and tendon destruction (P = 0.010). No statistically significant differences were found between the two groups regarding bone erosion (P = 0.196) or neurovascular bundle encasement (P = 0.165). CONCLUSIONS: Diffuse-type TSGCTs of digits presented as locally aggressive lesions with larger, multinodular, infiltrative masses exhibiting stronger hemosiderin deposition and more severe disease extents of articular, muscle, and tendon involvement than the localized type.
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Tumor de Células Gigantes de Bainha Tendinosa , Tumores de Células Gigantes , Humanos , Hemossiderina , Tumor de Células Gigantes de Bainha Tendinosa/diagnóstico por imagem , Tendões/diagnóstico por imagem , Tendões/patologia , Imageamento por Ressonância Magnética , Extremidades/patologia , Tumores de Células Gigantes/diagnóstico por imagemRESUMO
BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by immune dysregulation, pruritus, and abnormal epidermal barrier function. Compared with conventional mesenchymal stem cell (MSC), induced pluripotent stem cell (iPSC)-derived mesenchymal stem cell (iMSC) is recognized as a unique source for producing extracellular vesicles (EVs) because it can be obtained in a scalable manner with an enhanced homogeneity. Stimulation of iMSCs with inflammatory cytokines can improve the immune-regulatory, anti-inflammatory, and tissue-repairing potential of iMSC-derived EVs. RESULTS: Proteome analysis showed that IFN-γ-iMSC-EVs are enriched with protein sets that are involved in regulating interferon responses and inflammatory pathways. In AD mice, expression of interleukin receptors for Th2 cytokines (IL-4Rα/13Rα1/31Rα) and activation of their corresponding intracellular signaling molecules was reduced. IFN-γ-iMSC-EVs decreased itching, which was supported by reduced inflammatory cell infiltration and mast cells in AD mouse skin; reduced IgE receptor expression and thymic stromal lymphopoietin and NF-kB activation; and recovered impaired skin barrier, as evidenced by upregulation of key genes of epidermal differentiation and lipid synthesis. CONCLUSIONS: IFN-γ-iMSC-EVs inhibit Th2-induced immune responses, suppress inflammation, and facilitate skin barrier restoration, contributing to AD improvement.
Assuntos
Dermatite Atópica , Vesículas Extracelulares , Células-Tronco Mesenquimais , Camundongos , Animais , Dermatite Atópica/terapia , Dermatite Atópica/genética , Citocinas/metabolismo , Vesículas Extracelulares/metabolismo , Epiderme/metabolismo , Interferon gama/metabolismoRESUMO
BACKGROUND: With the increasing sport population, the number of patients with external snapping hip (ESH) has also increased. To detect and visualise pathological soft tissue changes, magnetic resonance imaging (MRI) has been 1 of the most useful modalities. However, only limited studies have investigated MRI and its clinical value in the treatment of ESH in the past. MATERIALS AND METHODS: Between May 2017 and November 2018, 104 patients were diagnosed with ESH at our institution. We excluded patients who did not undergo an MRI (n = 11), had complaint of bilateral symptom (n = 17), were not diagnosed hip problems previously (n = 2), and were lost-follow-up within 6 months (n = 19). After applying the exclusion criteria, 55 patients remained. We classified the patients into 2 groups according-MRI findings: tensed iliotibial band (ITB) and hypertrophied gluteus maximus (GM). We investigated the clinical findings, such as mean age, symptom duration, pain score, grading based on symptom severity, and other radiological findings such as soft tissue signal change and ITB thickness. The variables were compared between the groups. RESULTS: Between the 2 groups defined by MRI findings, the group characterised by tense ITB showed a relatively short symptom duration than the hypertrophied GM group (p < 0.001). No significant differences in the other variables were found between the groups. CONCLUSIONS: ESH has 2 types of MRI features. Compared with the hypertrophied GM group, the tense ITB group showed a shorter symptom duration and a more reversible status.
Assuntos
Artroplastia de Quadril , Artropatias , Artroscopia , Fascia Lata , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Humanos , Artropatias/cirurgia , Imageamento por Ressonância MagnéticaRESUMO
CONTEXT: The upregulation of TRIB3 (Tribbles homolog 3), a stress-inducible gene encoding a pseudokinase, has been implicated in the development of insulin resistance in the skeletal muscle and liver of patients with obesity and type 2 diabetes. However, there is little information regarding TRIB3 expression in human adipose tissue. OBJECTIVE: To investigate whether TRIB3 expression is dysregulated in human adipose tissue in the context of obesity and type 2 diabetes and whether TRIB3 expression in adipose tissues is associated with insulin resistance. METHODS: We measured metabolic parameters and TRIB3 expression in abdominal subcutaneous and visceral adipose tissue in obese (with or without type 2 diabetes) and normal-weight women. Regulation of TRIB3 expression was studied in human adipocytes. RESULTS: TRIB3 expression in both fat depots was higher in patients with obesity and/or type 2 diabetes; in addition, the expression level was significantly associated with insulin resistance. Incubating adipocytes under conditions mimicking the microenvironment of obese adipose tissue, including increased endoplasmic reticulum (ER) stress, induced TRIB3 expression. In human adipocytes, the overexpression of TRIB3 impaired insulin-stimulated protein kinase B (AKT) phosphorylation and caused dysregulation of the transcription of genes encoding bioactive molecules released from adipocytes, such as proinflammatory cytokines, adiponectin, and leptin. Pioglitazone, an insulin-sensitizing agent, reduced both these effects of TRIB3 and the ER stressor-induced expression of TRB3. CONCLUSION: Our data indicate that TRIB3 expression in adipose tissue is enhanced in patients with obesity and suggest that increased TRIB3 dysregulates adipocyte function, which may contribute to the development of insulin resistance.
Assuntos
Proteínas de Ciclo Celular/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Gordura Subcutânea Abdominal/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adulto , Proteínas de Ciclo Celular/análise , Células Cultivadas , Técnicas de Cocultura , Estresse do Retículo Endoplasmático , Feminino , Humanos , Resistência à Insulina , Gordura Intra-Abdominal/citologia , Macrófagos , Pessoa de Meia-Idade , Pioglitazona/farmacologia , Cultura Primária de Células , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Repressoras/análise , Gordura Subcutânea Abdominal/citologia , Regulação para Cima/efeitos dos fármacosRESUMO
Non-alcoholic fatty liver disease (NAFLD) is frequently associated with obesity, insulin resistance, and endoplasmic reticulum (ER) stress. Elevated circulating levels of the hepatokine leukocyte cell-derived chemotaxin-2 (LECT2) have also been noted in NAFLD; however, the mechanism underlying this association is unclear. To investigate a possible link between ER stress/unfolded protein response (UPR) signaling and LECT2 secretion, HepG2 cells were incubated with ER stress inducers with or without an ER stress-reducing chemical chaperone. Additionally, UPR pathway genes were knocked down and overexpressed, and a ChIP assay was performed. In diet-induced obese mice, hepatic expression of LECT2 and activating transcription factor 4 (ATF4) was measured. In HepG2 cells, LECT2 expression was increased by ER stressors, an effect blocked by the chemical chaperone. Among UPR pathway proteins, only knockdown of ATF4 suppressed ER stress-induced LECT2 expression, while overexpression of ATF4 enhanced LECT2 expression. The ChIP assay revealed that ATF4 binds to three putative binding sites on the LECT2 promoter and binding is promoted by an ER stress inducer. In steatotic livers of obese mice, LECT2 and ATF4 expression was concomitantly elevated. Our data indicate that activation of ER stress/UPR signaling induces LECT2 expression in steatotic liver; specifically, ATF4 appears to mediate upregulation of LECT2 transcription.