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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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The melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) comprise a subset of the â¼40 retinal ganglion cell types in the mouse retina and drive a diverse array of light-evoked behaviors from circadian photoentrainment to pupil constriction to contrast sensitivity for visual perception. Central to the ability of ipRGCs to control this diverse array of behaviors is the distinct complement of morphophysiological features and gene expression patterns found in the M1-M6 ipRGC subtypes. However, the genetic regulatory programs that give rise to subtypes of ipRGCs are unknown. Here, we identify the transcription factor Brn3b (Pou4f2) as a key genetic regulator that shapes the unique functions of ipRGC subtypes and their diverse downstream visual behaviors.
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OBJECTIVES: The aim of this study was to analyze the relationship between objective social isolation (SI) and unmet medical needs (UMN) in adults aged 19 and older. METHODS: A cross-sectional analysis was conducted of 208 619 adults aged 19 and older, excluding missing data, using the 2019 Korea Community Health Survey. To analyze the association between objective SI and UMN, the chi-square test and logistic regression analysis were performed. RESULTS: The prevalence of UMN was 1.14 times higher (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.06 to 1.23) among those with SI than among those without SI, and the OR for groups with 5 SI types was 2.77 (95% CI, 1.86 to 4.12) compared to those with no SI types. In addition, a stratified analysis by age group showed that the association between SI and UMN existed even in groups under 64 years old. However, among those aged 65 and older, SI was associated with an OR of 1.53 (95% CI, 1.37 to 1.71) for UMN compared to non-SI. As the number of SI types increased, the prevalence of UMN also increased, indicating a strong association between SI and UMN in older adults. CONCLUSIONS: This study found that individuals with SI experienced UMN due to fear and anxiety about interpersonal relationships. Therefore, based on the results of this cross-sectional study, it is necessary to investigate the causal relationship between SI and UMN through future longitudinal data.
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Aislamiento Social , Humanos , Estudios Transversales , Persona de Mediana Edad , República de Corea/epidemiología , Aislamiento Social/psicología , Femenino , Adulto , Masculino , Anciano , Adulto Joven , Necesidades y Demandas de Servicios de Salud/estadística & datos numéricos , Prevalencia , Modelos Logísticos , Anciano de 80 o más Años , Encuestas EpidemiológicasRESUMEN
Mine operational safety is an important aspect of maintaining the operational continuity of a mining area. In this study, we used the InSAR time series to analyze land surface changes using the ICOPS (improved combined scatterers with optimized point scatters) method. This ICOPS method combines persistent scatterers (PS) with distributed scatterers (DS) to increase surface deformation analysis's spatial coverage and quality. One of the improvements of this study is the use of machine learning in postprocessing, based on convolutional neural networks, to increase the reliability of results. This study used data from the Sentinel-1 SAR C-band satellite during the 2016-2022 observation period at the Musan mine, North Korea. In the InSAR surface deformation time analysis, the maximum average rate of land subsidence was approximately > 15.00 cm per year, with total surface deformation of 170 cm and 70 cm for the eastern dumping area and the western dumping area, respectively. Analyzing the mechanism of land surface changes also involved evaluating the geological conditions in the Musan mining area. Our research findings show that combining machine learning and statistical methods has great potential to enhance the understanding of mine surface deformation.
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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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OBJECTIVE: The Children in Disaster: Evaluation and Recovery (CIDER) program in Korea was developed to treat children and adolescents exposed to trauma. This study aimed to demonstrate the effectiveness of the CIDER through a comparison with controls. METHODS: A total of 85 participants consisted of the intervention group (n=41) and control group (n=44). We assessed the changes in trauma-related symptoms, depression, anxiety, and improvements in quality of life before and after the intervention. RESULTS: In total, bullying and school violence (44.7%) were the most common trauma, followed by sexual abuse (17.6%). Acute stress disorder and post-traumatic stress disorder (PTSD) accounted for 41.2%, and attention-deficit/hyperactivity disorder (ADHD) and developmental disorder were the most common comorbidities (51.8%). The symptoms of trauma, depression, anxiety, and quality of life improved significantly in the intervention group, while the control group did not show significant changes. CONCLUSION: Compared with the control group, the CIDER improved symptoms and quality of life in children and adolescents who had experienced trauma. The CIDER program was practical and easy to apply, even for different ages, types of traumas, and comorbidities.
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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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Lesión Renal Aguda , Vesículas Extracelulares , Receptores Activados del Proliferador del Peroxisoma , Animales , Humanos , Ratones , Lesión Renal Aguda/patología , Cisplatino , Vesículas Extracelulares/metabolismo , Inflamación/metabolismo , Receptores Activados del Proliferador del Peroxisoma/agonistas , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Células Madre Mesenquimatosas/metabolismoRESUMEN
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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PURPOSE: The aim of the study is to evaluate the stage 3 findings of the 2019 revision of the Association Research Circulation Osseous (ARCO) staging system for osteonecrosis of the femoral head between 3A and 3B and the relationship with bone resorption area. MATERIALS AND METHODS: We retrospectively enrolled 87 patients with ARCO stage 3 osteonecrosis of the femoral head, divided into stage 3A (n = 73) and 3B (n = 14). The revised stage 3 findings included subchondral fracture, fracture in necrotic portion, and flattening of the femoral head and were compared between stage 3A and 3B. The association between these findings and the causative features of bone resorption area was also evaluated. RESULTS: All stage 3 cases had subchondral fractures. In stage 3A, these fractures were generated by crescent sign (41.1%) and by fibrovascular reparative zone in 58.9%; however, in stage 3B, fibrovascular reparative zone generated 92.9% of these fractures and crescent sign only 7.1% with statistical significance ( P = 0.034). Necrotic portion fracture was noted in 36.7% and femoral head flattening was observed in 14.9% of all stage 3. Necrotic portion fracture (92.9% vs 26.0%) and femoral head flattening (71.4% vs 4.1%) were observed more frequently in stage 3B than 3A ( P < 0.001). Almost all subchondral fractures by fibrovascular reparative zone (96.4%) and necrotic portion fracture (96.9%), and all femoral head flattening was presented with bone resorption area with expanding areas. CONCLUSIONS: The ARCO stage 3 descriptions reflect severity in this order: subchondral fracture, necrotic portion fracture, and femoral head flattening. More severe findings are usually associated with expanding bone resorption areas.
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Resorción Ósea , Necrosis de la Cabeza Femoral , Fracturas Óseas , Humanos , Necrosis de la Cabeza Femoral/diagnóstico por imagen , Necrosis de la Cabeza Femoral/complicaciones , Cabeza Femoral/diagnóstico por imagen , Estudios Retrospectivos , Resorción Ósea/diagnóstico por imagen , Resorción Ósea/complicacionesRESUMEN
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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Dermatitis Atópica , Exosomas , Células Madre Pluripotentes Inducidas , Células Madre Mesenquimatosas , Animales , Humanos , Ratones , Citocinas/metabolismo , Dermatitis Atópica/tratamiento farmacológico , Exosomas/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Inflamación/metabolismo , Interferón gamma/metabolismo , Células Madre Mesenquimatosas/metabolismo , ARN Mensajero/metabolismo , Piel/metabolismo , Agua/metabolismoRESUMEN
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 las Vainas Tendinosas , Articulación de la Rodilla , Humanos , Estudios Retrospectivos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Tendones/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
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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Development of FokI-based engineered nucleases has been a platform technology that enables creation of novel sequence-specific nucleases as well as structure-specific nucleases. Z-DNA-specific nucleases have been constructed by fusing a Z-DNA-binding domain to the nuclease domain of FokI (FN). In particular, Zαα, an engineered Z-DNA-binding domain with a high affinity, is an ideal fusion partner to generate a highly efficient Z-DNA-specific cutter. Here, we describe construction, expression, and purification of Zαα-FOK (Zαα-FN) nuclease in detail. In addition, Z-DNA-specific cleavage is demonstrated by the use of Zαα-FOK.
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ADN de Forma Z , Proteínas Recombinantes de Fusión/metabolismo , Dedos de Zinc , Conformación Molecular , Desoxirribonucleasas de Localización Especificada Tipo II/metabolismoRESUMEN
(1) Background: A delaminated tear is described as a horizontal split in the tendon substance. This review summarizes the clinical and radiologic characteristics of delaminated tears of the rotator cuff. (2) Methods: Initial radiological characteristics of a delaminated tear include the horizontal component of a partial-thickness tear determined using magnetic resonance (MR) arthrography. As demonstrated using indirect MR arthrography, the tear gradually progresses to be defined as either horizontal intrasubstantial splitting of the bursal and articular layers or differential retraction of the bursal and articular layers. (3) Results: The existence of delaminated tears is a poor prognostic factor in functional and morphologic outcomes after the repair of rotator cuff tendons and many surgical techniques have been introduced to solve this problem. Although the presence of a delaminated tear does not affect the arthroscopic repair outcome, the presence of medium-to-large, retracted delaminated tears may be an adverse negative prognostic factor after single-row repair. (4) Conclusion: Advances in imaging and surgical techniques have improved the detection of delaminated rotator cuff tears. Preoperative identification of delaminated tears on magnetic resonance imaging is clinically important because tailored surgical repair techniques must be chosen for successful outcomes.
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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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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.