RESUMO
BACKGROUND: To identify physical activity (PA) trajectories in adults with or at risk of knee osteoarthritis and to evaluate the association of PA trajectories with incident knee replacement (KR). METHODS: This study used data from the Osteoarthritis Initiative. The Physical Activity Scale for the Elderly and the KR were assessed annually from baseline to 9 years. Individuals were included if they did not undergo KR surgery at baseline and had data on PA at ≥ 1 visit before KR. Latent class growth mixture Modeling was used to identify the optimal trajectories of PA before KR. Log-binomial regression models were used to assess the association between PA trajectories and the risk of KR. Data analyses were conducted in all individuals and those with radiographic osteoarthritis (ROA) and significant knee pain (Western Ontario and McMaster Osteoarthritis Index pain score of ≥ 5 on a 0-20 scale) at baseline, respectively. RESULTS: Of 4731 participants (mean age 61.1 years, 58.5% female), four distinct and slightly declined PA trajectories were identified. Compared to individuals with a "Low" PA trajectory, those with "Medium-low", "Medium-high", or "High" PA trajectories were not significantly associated with the risk of KR (risk ratios: 0.97-1.19, all p > 0.05). Similar PA trajectories and associations with the risk of KR were observed in the subgroups of individuals with radiographic osteoarthritis and those with significant knee pain at baseline, respectively. CONCLUSION: In participants with or at risk of knee osteoarthritis, PA slightly declines over time and may play no role in the risk of KR.
Assuntos
Artroplastia do Joelho , Exercício Físico , Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/fisiopatologia , Artroplastia do Joelho/tendências , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Exercício Físico/fisiologia , Fatores de Risco , Estudos Longitudinais , Fatores de TempoRESUMO
Targeting telomere maintenance has emerged as a promising strategy for hepatocellular carcinoma (HCC) treatment. However, given the duality of the telomere-telomerase axis in telomere maintenance, a comprehensive strategy is urgently needed. Herein, we develop a poly(amino acid) (D-PAAs)-based strategy for spatiotemporal codelivery of telomerase inhibitor, BIBR1523, and AKT inhibitor, isobavachalcone. By leveraging D-PAAs' modifiability, we synthesize polymer-inhibitor conjugates (PB and PI) and a folic acid-decorated tumor-targeting vector (PF). These building blocks undergo micellization to fabricate a codelivery nanomedicine (P-BI@P-FA) by exploiting D-PAAs' noncovalent assembly. P-BI@P-FA improves the pharmacokinetics, tumor selectivity, and bioavailability of small molecule inhibitors and initiates a dual telomere-specific inhibition by combining telomerase deactivation with telomere disruption. Furthermore, a hybrid tumor-targeting magnetic nanosystem is designed using D-PAAs and manganese dioxide to showcase magnetic resonance imaging capacities. Our D-PAAs-based strategy addresses the pressing need for telomere-specific HCC treatment while allowing for diagnostic application, presenting a promising avenue for nanomedicine design.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Imageamento por Ressonância Magnética , Nanomedicina , Telomerase , Telômero , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Telomerase/antagonistas & inibidores , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Humanos , Nanomedicina/métodos , Telômero/metabolismo , Imageamento por Ressonância Magnética/métodos , Animais , Camundongos , Linhagem Celular Tumoral , Aminoácidos/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/uso terapêuticoRESUMO
Cardiac magnetic resonance imaging (CMR) is the gold standard for cardiac function assessment and plays a crucial role in diagnosing cardiovascular disease (CVD). However, its widespread application has been limited by the heavy resource burden of CMR interpretation. Here, to address this challenge, we developed and validated computerized CMR interpretation for screening and diagnosis of 11 types of CVD in 9,719 patients. We propose a two-stage paradigm consisting of noninvasive cine-based CVD screening followed by cine and late gadolinium enhancement-based diagnosis. The screening and diagnostic models achieved high performance (area under the curve of 0.988 ± 0.3% and 0.991 ± 0.0%, respectively) in both internal and external datasets. Furthermore, the diagnostic model outperformed cardiologists in diagnosing pulmonary arterial hypertension, demonstrating the ability of artificial intelligence-enabled CMR to detect previously unidentified CMR features. This proof-of-concept study holds the potential to substantially advance the efficiency and scalability of CMR interpretation, thereby improving CVD screening and diagnosis.
Assuntos
Inteligência Artificial , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/diagnóstico , Feminino , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Imagem Cinética por Ressonância Magnética/métodos , Programas de Rastreamento/métodos , Idoso , AdultoRESUMO
Clear cell renal cell carcinoma (ccRCC) is the most common form of RCC. It is characterized by resistance to traditional radiotherapy and chemotherapy, as well as an unfavorable clinical prognosis. Although TYMP is implicated in the advancement of tumor progression, the role of TYMP in ccRCC is still not understood. Heightened TYMP expression was identified in ccRCC through database mining and confirmed in RCC cell lines. Indeed, TYMP knockdown impacted RCC cell proliferation, migration, and invasion in vitro. TYMP showed a positive correlation with clinicopathological parameters (histological grade, pathological stage). Moreover, patients with high TYMP expression were indicative of poor prognosis in TCGA-ccRCC and external cohorts. The results of single-cell analysis showed that the distribution of TYMP was predominantly observed in monocytes and macrophages. Furthermore, there is a significant association between TYMP and immune status. Methylation analysis further elucidated the relationship between TYMP expression and multiple methylation sites. Drug sensitivity analysis unveiled potential pharmaceutical options. Additionally, mutation analyses identified an association between TYMP and the ccRCC driver genes like BAP1 and ROS1. In summary, TYMP may serve as a reliable prognostic indicator for ccRCC.
Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias Renais/mortalidade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Prognóstico , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Masculino , Estudos de Coortes , Feminino , Proliferação de Células , Metilação de DNA , Movimento Celular , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Cardiac magnetic resonance (CMR) is a diagnostic tool that provides precise and reproducible information about cardiac structure, function, and tissue characterization, aiding in the monitoring of chemotherapy response in patients with light-chain cardiac amyloidosis (AL-CA). This study aimed to evaluate the feasibility of CMR in monitoring responses to chemotherapy in patients with AL-CA. MATERIALS AND METHODS: In this prospective study, we enrolled 111 patients with AL-CA (50.5% male; median age, 54 [interquartile range, 49-63] years). Patients underwent longitudinal monitoring using biomarkers and CMR imaging. At follow-up after chemotherapy, patients were categorized into superior and inferior response groups based on their hematological and cardiac laboratory responses to chemotherapy. Changes in CMR findings across therapies and differences between response groups were analyzed. RESULTS: Following chemotherapy (before vs. after), there were significant increases in myocardial T2 (43.6 ± 3.5 ms vs. 44.6 ± 4.1 ms; P = 0.008), recovery in right ventricular (RV) longitudinal strain (median of -9.6% vs. -11.7%; P = 0.031), and decrease in RV extracellular volume fraction (ECV) (median of 53.9% vs. 51.6%; P = 0.048). These changes were more pronounced in the superior-response group. Patients with superior cardiac laboratory response showed significantly greater reductions in RV ECV (-2.9% [interquartile range, -8.7%-1.1%] vs. 1.7% [-5.5%-7.1%]; P = 0.017) and left ventricular ECV (-2.0% [-6.0%-1.3%] vs. 2.0% [-3.0%-5.0%]; P = 0.01) compared with those with inferior response. CONCLUSION: Cardiac amyloid deposition can regress following chemotherapy in patients with AL-CA, particularly showing more prominent regression, possibly earlier, in the RV. CMR emerges as an effective tool for monitoring associated tissue characteristics and ventricular functional recovery in patients with AL-CA undergoing chemotherapy, thereby supporting its utility in treatment response assessment.
Assuntos
Cardiomiopatias , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Estudos de Viabilidade , Amiloidose/diagnóstico por imagem , Amiloidose/tratamento farmacológico , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico por imagem , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Resultado do Tratamento , Imagem Cinética por Ressonância Magnética/métodos , Antineoplásicos/uso terapêuticoAssuntos
Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Dexametasona , Amiloidose de Cadeia Leve de Imunoglobulina , Humanos , Bortezomib/administração & dosagem , Bortezomib/efeitos adversos , Bortezomib/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Amiloidose de Cadeia Leve de Imunoglobulina/tratamento farmacológico , Amiloidose de Cadeia Leve de Imunoglobulina/mortalidade , Amiloidose de Cadeia Leve de Imunoglobulina/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Masculino , Feminino , Estudos Prospectivos , Idoso , Resultado do Tratamento , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
BACKGROUND AND PURPOSE: [68Ga]Ga-PSMA PET imaging has been extensively utilized for the detection of biochemical recurrence (BCR) in prostate cancer. However, the detection rate declines to merely 10-40% when PSA levels are < 0.2 ng/mL employing short axial field-of-view (SAFOV) PET. Prior studies exhibited superior detection rates with total-body [68Ga]Ga-PSMA-11 PET compared to SAFOV [68Ga]Ga-PSMA-11 PET in BCR patients with PSA > 0.2 ng/mL. Nevertheless, the diagnostic utility of total-body [68Ga]Ga-PSMA-11 PET for BCR patients when PSA is < 0.2 ng/mL remains unclear. This study aimed to assess whether total-body [68Ga]Ga-PSMA-11 PET/CT could improve the detection rate compared to SAFOV [68Ga]Ga-PSMA-11 PET/CT in BCR patients with PSA < 0.2 ng/mL. METHODS: Eighty BCR patients with PSA < 0.2 ng/mL underwent total-body [68Ga]Ga-PSMA-11 PET/CT. These patients were matched by baseline qualities to another 80 patients who received SAFOV [68Ga]Ga-PSMA-11 PET/CT. The detection rates of total-body [68Ga]Ga-PSMA-11 PET/CT and SAFOV [68Ga]Ga-PSMA-11 PET/CT were compared utilizing a chi-square test and stratified analysis. Image quality of total-body [68Ga]Ga-PSMA PET/CT and SAFOV [68Ga]Ga-PSMA-11 PET/CT was assessed based on subjective scoring and objective parameters. The objective parameters measured were SUVmax, SUVmean, standard deviation (SD) of SUV, and signal-to-noise ratio (SNR) of liver and gluteus maximus. RESULTS: The image quality of total-body [68Ga]Ga-PSMA PET/CT was superior to that of SAFOV [68Ga]Ga-PSMA-11 PET/CT in both early and delayed scans. The detection rate of total-body [68Ga]Ga-PSMA PET/CT for BCR patients with PSA < 0.2 ng/mL was significantly higher than that of SAFOV [68Ga]Ga-PSMA-11 PET/CT (73.75% vs. 43.75%, P < 0.001). Total-body [68Ga]Ga-PSMA PET/CT resulted in noteworthy modifications to the treatment regimen when contrasted with SAFOV [68Ga]Ga-PSMA-11 PET/CT. CONCLUSIONS: In BCR patients with PSA < 0.2 ng/mL, total-body [68Ga]Ga-PSMA-11 PET/CT not only demonstrated a significantly higher detection rate compared to SAFOV [68Ga]Ga-PSMA-11 PET/CT but also led to significant alterations in treatment regimens.
Assuntos
Ácido Edético , Isótopos de Gálio , Radioisótopos de Gálio , Oligopeptídeos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Antígeno Prostático Específico , Prostatectomia , Neoplasias da Próstata , Humanos , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Ácido Edético/análogos & derivados , Idoso , Antígeno Prostático Específico/sangue , Pessoa de Meia-Idade , Imagem Corporal Total/métodos , Recidiva , Estudos Retrospectivos , Recidiva Local de Neoplasia/diagnóstico por imagemRESUMO
BACKGROUND: This study investigated the trends, motivations and preferences of rhinoplasty in China. METHODS: Data on rhinoplasty were collected from Xiaohongshu and analyzed for trends. Text analysis and word frequency statistics were performed on the notes and comments using Python modules. RESULTS: We obtained 1065 notes with 102,153 comments, 239,383 collections and 640,579 likes. The number of rhinoplasty-related publications increased annually, correlating with per capita disposable income of households (DI) growth (r2 = 0.609, P = 0.041 < 0.05). In the Southern provinces, there was a notably higher volume of publications compared to the Northern provinces (P = 0.001). Furthermore, a significant correlation was observed between publication data, population size, and the DI (r2 = 0.786, P < 0.001). The nasal tip (3197) and nasion (1409) were the most mentioned nasal subunits. "Good-looking" (9672) and "natural" (2811) were the most used words to describe the nose shape. The "doctor" (4377), the "hospital" (2182) and "hyaluronic acid" (2106) were the most mentioned rhinoplasty procedure related vocabulary. CONCLUSIONS: Discussions about rhinoplasty in China are increasing, and more people express their desire for rhinoplasty on social networks, related to China's DI growth. The Southern provinces show a higher inclination toward these discussions, a trend that correlates with our findings of a positive association between NOPs and both DI and population size. Netizens pay more attention to the shape of nasal tip and nasion, and prefer the good-looking and natural appearance. Most people consider autologous cartilage or hyaluronic acid injection for rhinoplasty. Doctors are the primary consideration for patients. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Assuntos
Preferência do Paciente , Rinoplastia , Mídias Sociais , Adulto , Feminino , Humanos , Masculino , China , População do Leste Asiático , Estética , Rinoplastia/métodos , Rinoplastia/psicologiaRESUMO
BACKGROUND: To explore the role of leukemia inhibitory factor (LIF) in periodontitis via in vivo and in vitro experiments. METHODS: The second upper molar of LIF knockout mice and their wild-type littermates were ligated for 8 days. Micro-computed tomography (micro-CT), histological analysis, and quantitative real-time polymerase chain reaction (qRT-PCR) were performed. The expression levels of proinflammatory cytokines were examined in mouse bone marrow derived macrophages and human periodontal ligament fibroblasts (HPDLFs) after lipopolysaccharide (LPS) treatment. RESULTS: LIF deficiency promoted alveolar bone loss, inflammatory cells infiltration, osteoclasts formation and collagen fiber degradation in ligature-induced mouse, along with higher expressions of proinflammatory cytokines, including interleukin-6 (IL6), IL-1ß (IL1B), tumor necrosis factor-α (TNFA), matrix metalloproteinase 13 (MMP13), and RANKL/OPG ratio. Additionally, LIF deletion led to higher expression levels of these proinflammatory cytokines in mouse bone marrow-derived macrophages from both femur and alveolar bone and HPDLFs when treated with LPS. Administration of recombined LIF attenuated TNFA, IL1B, and RANKL/OPG ratio in HPDLFs. CONCLUSIONS: These findings indicate that LIF deficiency promotes the progress of periodontitis via modulating immuno-inflammatory responses of macrophages and periodontal ligament fibroblasts, and the application of LIF may be an adjunctive treatment for periodontitis to resolute inflammation.
RESUMO
BACKGROUND: NA OBJECTIVE: Evaluate the safety and feasibility of platelet-rich plasma (PRP) in the treatment of giant congenital melanocytic nevi (GCMN) in children with human acellular dermal matrix (HADM) transplantation. PATIENTS AND METHODS: A total of 22 children with GCMN were included in the study. They were divided into an experimental and a control group. The experimental group used the method of HADM with Razor Autologous Skin Graft combined with PRP to repair skin and soft tissue defects after giant nevus resection (Group A, n = 11). The control group was treated with HADM with Razor Autologous Skin Graft (Group B, n = 11) only. To compare the survival rate of skin grafts, we used the Vancouver Scar Scale (VSS) for the postoperative skin graft area and the Patient and Observer Scar Assessment Scale (POSAS) to compare the two groups of patients. RESULTS: There was no statistically significant difference in age, gender, location of giant nevi, and pathological classification between Group A and Group (P > 0.05). The survival rate of skin grafting and the VSS and POSAS scores of scar tissue in group A were superior to those of group B (P < 0.05). CONCLUSIONS: PRP has improved the survival rate of composite skin grafting in children with GCMN, and long-term satisfactory prognosis of scar healing. Therefore, we consider this treatment method a valuable contribution to clinical practice.
Assuntos
Derme Acelular , Nevo Pigmentado , Plasma Rico em Plaquetas , Neoplasias Cutâneas , Criança , Humanos , Transplante de Pele/métodos , Cicatriz/cirurgia , Nevo Pigmentado/cirurgia , Nevo Pigmentado/congênitoRESUMO
Sorafenib, FDA-approved therapy for patients with advanced hepatocellular carcinoma (HCC), leads to limited improvement in overall survival. However, it may indirectly impact the expansion and activity of natural killer (NK) cells. While NK cell-based immunotherapies generally exhibit favorable safety profiles, their effectiveness in controlling solid tumor growth is constrained, primarily due to the absence of antigen specificity and suboptimal expansion and persistence within the tumor microenvironment. In this study, we postulated that enhancing NK cell functionality via cytokine activation could bolster their viability and cytotoxic capabilities, leading to an improved therapeutic response when combined with sorafenib. Memory-like (ML)-NK cells were generated through the supplementation of optimal concentrations of interleukin (IL)-12 and IL-18 cytokines. Following a single day of treatment, cytotoxicity against rat and human HCC cells was evaluated via flow cytometry analysis. A rat HCC model was developed in 30 animals via subcapsular implantation and assigned to control, NK, sorafenib, ML-NK, and combination groups. Sorafenib was administered orally, and NK cells were delivered via the intrahepatic artery. Tumor growth was measured one week after treatment evaluation. Therapeutic efficacy during in-vitro and in-vivo analysis was investigated through a one-way ANOVA test, followed by pairwise two-tailed Student t-tests, considering P < 0.05 statistically significant. The in-vitro experiment results demonstrated that sorafenib and conventional NK cell therapies induced more substantial cell death than the control group (P < 0.01). ML NK cells significantly improved cell death compared to conventional NK cell immunotherapy. Furthermore, sorafenib in combination with ML-NK cells significantly decreased the viability of HCC cells (P < 0.05) compared to sorafenib plus conventional NK cell combination therapy. In vivo experiments have shown that sorafenib and ML-NK cell immunotherapy reduced the growth rate of HCC tumors compared to conventional NK immunotherapy and control groups. Notably, a combination of sorafenib and ML-NK cell immunochemotherapy resulted in the most significant suppression of tumor growth when compared to other therapies. In conclusion, our experimental findings demonstrate that the concurrent administration of sorafenib and ML-NK immunotherapy enhances cytotoxicity against HCC by optimizing the therapeutic response through cytokine activation, resulting in a significant decrease in tumor growth.
RESUMO
Vitamin K (VK) comprises a group of substances with chlorophyll quinone bioactivity and exists in nature in the form of VK1 and VK2. As its initial recognition originated from the ability to promote blood coagulation, it is known as the coagulation vitamin. However, based on extensive research, VK has shown potential for the prevention and treatment of various diseases. Studies demonstrating the beneficial effects of VK on immunity, antioxidant capacity, intestinal microbiota regulation, epithelial development, and bone protection have drawn growing interest in recent years. This review article focuses on the mechanism of action of VK and its potential preventive and therapeutic effects on infections (eg, asthma, COVID-19), inflammation (eg, in type 2 diabetes mellitus, Alzheimer's disease, Parkinson's disease, cancer, aging, atherosclerosis) and autoimmune disorders (eg, inflammatory bowel disease, type 1 diabetes mellitus, multiple sclerosis, rheumatoid arthritis). In addition, VK-dependent proteins (VKDPs) are another crucial mechanism by which VK exerts anti-inflammatory and immunomodulatory effects. This review explores the potential role of VK in preventing aging, combating neurological abnormalities, and treating diseases such as cancer and diabetes. Although current research appoints VK as a therapeutic tool for practical clinical applications in infections, inflammation, and autoimmune diseases, future research is necessary to elucidate the mechanism of action in more detail and overcome current limitations.
RESUMO
An amino-assisted [3 + 2] cycloaddition strategy of nitrile imines with o-aminotrifluoroacetophenones has been explored, thus providing functionalized 1,3,4-oxadiazolines bearing CF3-quaternary centers in good to excellent yields in the presence of K2CO3 under mild conditions. The amino groups located at the ortho-position of trifluoroacetophenone might play a crucial role in the present cyclization. The MTT assay shows that the 1,3,4-oxadiazoline derivatives could be potential candidates for the treatment of head and neck cancers.
RESUMO
OBJECTIVE: To identify bone marrow lesion (BML) trajectories over 4 years and their demographic and structural predictors in middle-aged and older adults with or at increased risk of knee osteoarthritis (OA). METHODS: A total of 614 participants (mean age 61 years, 62% female) from the Osteoarthritis Initiative cohort (OAI) were included. BMLs in 15 anatomical locations of the knee were measured annually from baseline to 4 years using the Magnetic Resonance Imaging Osteoarthritis Knee Score (MOAKS) method. BML trajectories were determined using latent class mixed models (LCMMs). Multinomial logistic regression was used to examine baseline characteristics that predicted BML trajectories. RESULTS: Three distinct BML trajectories were identified: "Mild-stable BMLs" (25.9%), "Moderate-stable BMLs" (66.4%), and "Rapid-rise BMLs" (7.7%). Compared to the "Mild-stable BMLs" trajectory, current smokers were more likely to be in the "Moderate-stable BMLs" (odds ratio [OR] 2.089, P < 0.001) and "Rapid-rise" (OR 2.462, P < 0.001) trajectories. Moreover, female sex and meniscal tears were associated with an increased risk of being in the "Rapid-rise BMLs" trajectory (OR 2.023 to 2.504, P < 0.05). Participants who had higher education levels and drank more alcohol were more likely to be in the "Rapid-rise BMLs" trajectory (OR 1.624 to 3.178, P < 0.05) and less likely to be in the "Moderate-stable BMLs" trajectory (OR 0.668 to 0.674, P < 0.05). CONCLUSIONS: During the 4-year follow-up, most participants had relatively stable BMLs, few had enlarged BMLs, and no trajectory of decreased BMLs was identified. Sociodemographic factors, lifestyle, and knee structural pathology play roles in predicting distinct BML trajectories.
Assuntos
Imageamento por Ressonância Magnética , Osteoartrite do Joelho , Humanos , Feminino , Masculino , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Fatores de Risco , Doenças da Medula Óssea/diagnóstico por imagem , Progressão da Doença , Idoso , Medula Óssea/diagnóstico por imagem , Medula Óssea/patologiaRESUMO
A large animal model of chronic coronary artery disease (CAD) is crucial for the understanding the underlying pathophysiological processes of chronic CAD and consequences for cardiac structure and function. The goal of this study was to develop a chronic model of CAD in a swine model and to evaluate the changes of myocardial structure, myocardial motility, and myocardial viability during coronary stenosis. A total of 30 swine (including 24 experimental animals and 6 controls) were enrolled. The chronic ischemia model was constructed by using Ameroid constrictor in experimental group. The 24 experimental animals were further divided into 4 groups (6 animals in each group) and were sacrificed at 1, 2, 3 and 4 weeks after operation for pathological examination, respectively. Cardiac magnetic resonance (CMR) was performed preoperatively and weekly postoperatively until sacrificed both in experimental and control group. CMR cine images, rest/adenosine triphosphate (ATP) stress myocardial contrast perfusion and LGE were performed and analyzed. The rest wall thickening (WT) score was calculated from rest cine images. The MPRI (myocardial perfusion reserve index) and MPR (myocardial perfusion reserve) were calculated based on rest and stress perfusion images. Pathology staining including triphenyltetrazolium chloride, HE and picrosirus red staining were performed after swine were sacrificed and collagen volume fraction (CVF) was calculated. The time to formation of ischemic, hibernating, and infarcted myocardium was recorded. In experimental group, from 1w to 4w after surgery, the rest WT score decreased gradually from 35.2 ± 2.0%, 32.0 ± 2.9% to 30.5 ± 3.0% and finally 29.06 ± 1.78%, p < 0.001. Left ventricular ejection fraction was gradually impaired after modeling (58.9 ± 12.6%, 56.3 ± 10.1%, 55.3 ± 9.0%, 53.8 ± 9.9%, respectively). And the MPR and MPRI also decreased stepwise with extent of surgery time (MPRI dropped from 2.1 ± 0.4, 2.0 ± 0.2 to 1.8 ± 0.3 and finally 1.7 ± 0.1, p = 0.004; MPR dropped from 2.3 ± 0.4, 2.1 ± 0.2 to 1.9 ± 0.4 and finally 1.8 ± 0.1, p < 0.001). Stronger associations between MPR, MPRI and CVF were paralleled lower wall thickening scores in fibrosis-affected areas. The ischemic myocardium was first appeared in the first week after surgery (involving ten segments), hibernated myocardium was first appeared in the second week after surgery (involving seventeen segments). LGE was first appeared in eight swine in the third weeks after surgery (16 segments). At 4w after surgery, average 9.6 g scar tissue was found among 6 swine. At the same time, histological analysis established the presence of fibrosis and ongoing apoptosis in the infarcted area. In conclusion, our study provided valuable insights into the pathophysiological processes of chronic CAD and its consequences for cardiac structure and function in a large animal model through combining myocardial motion and stress perfusion.
Assuntos
Cardiomiopatias , Isquemia Miocárdica , Imagem de Perfusão do Miocárdio , Suínos , Animais , Volume Sistólico , Adenosina , Valor Preditivo dos Testes , Função Ventricular Esquerda , Isquemia Miocárdica/patologia , Isquemia , Espectroscopia de Ressonância Magnética , Fibrose , Cardiomiopatias/diagnóstico por imagem , Cardiomiopatias/etiologia , Circulação Coronária/fisiologia , Imagem Cinética por Ressonância Magnética/métodos , Imagem de Perfusão do Miocárdio/métodosRESUMO
RATIONALE AND OBJECTIVES: It is still challenging for cardiac magnetic resonance (CMR) to detect ischemic heart disease (IHD) without the use of gadolinium contrast. We aimed to evaluate the potential value of adenosine triphosphate (ATP) stress myocardial strain derived from feature tracking (FT) as a novel method for detecting IHD in a swine model. MATERIALS AND METHODS: CMR cines, myocardial perfusion imaging at rest and during ATP stress, and late gadolinium enhancement were obtained in both control and IHD swine. Normal, remote, ischemic, and infarcted myocardium were analyzed. The diagnostic accuracy of myocardial strain for infarction and ischemia was assessed using coronary angiography and pathology as reference. RESULTS: Eleven IHD swine and five healthy control swine were enrolled in this study. Strain parameters, even at rest, were associated with myocardial ischemia and infarction(all p < 0.05). The area under receiver operating characteristic curve (AUC) values of all strain parameters for detecting infarcted myocardium exceeded 0.900 (all p < 0.05). The AUC values for detecting ischemic myocardium were as follows: 0.906 and 0.847 for stress and rest radial strain, 0.763 and 0.716 for stress and rest circumferential strain, 0.758 and 0.663 for stress and rest longitudinal strain (all p < 0.001). Heat maps demonstrated that all strain parameters showed mild to moderate correlations with the stress myocardial blood flow and myocardial perfusion reserve (all p < 0.05). CONCLUSION: CMR-FT-derived ATP stress myocardial strain shows promise as a noninvasive method for detecting myocardial ischemia and infarction in an IHD swine model, with rest strain parameters offering potential as a needle-free diagnostic option.
Assuntos
Isquemia Miocárdica , Imagem de Perfusão do Miocárdio , Suínos , Animais , Trifosfato de Adenosina , Meios de Contraste , Gadolínio , Valor Preditivo dos Testes , Isquemia Miocárdica/diagnóstico por imagem , Miocárdio/patologia , Infarto/patologia , Imagem Cinética por Ressonância Magnética , Imagem de Perfusão do Miocárdio/métodosRESUMO
BACKGROUND AND PURPOSE: The pre-surgical estimation of lymph node (LN) metastasis in colorectal cancer (CRC) poses a significant diagnostic predicament. The associations between LN morphology, density, and metabolic heterogeneity and LN metastasis status in CRCs have been seldomly examined through the lens of radiomics. This research aimed to assess 2-[18F]FDG PET-based quantification of intratumoral metabolic heterogeneity for predicting lymph node metastasis in patients with colorectal cancer. MATERIALS AND METHODS: The construction of the model utilized data from 264 CRC patients, all of whom underwent preoperative 2-[18F]FDG PET/CT. Radiomic features were extracted from PET and CT images of LNs. Least absolute shrinkage and selection operator (LASSO) regression was implemented for selecting pertinent imaging features with a tenfold cross-validation. The predictive accuracy for LN metastasis status was juxtaposed against traditional methodologies (comprising CT-reported LN status and PET/CT-reported LN status) by deploying the receiver operating characteristic (ROC) curve analysis. The radiomics signature was evaluated based on discrimination, calibration, and clinical utility parameters. The model was further subjected to validation using an independent cohort of 132 patients from the period of January 2012 to June 2020. RESULTS: The radiomics model was composed of eight significant radiomic features (five from PET and three from CT), encapsulating metabolic and density heterogeneity. The radiomics signature (area under the curve (AUC), 0.908) showcased a significantly superior performance compared to CT-reported LN status (AUC, 0.563, P < 0.001) and PET/CT-reported LN status (AUC, 0.64, P < 0.001) for predicting LN-positive or LN-negative status. The radiomics signature (AUC, 0.885) also showcased a significantly superior performance compared to CT-reported LN status (AUC, 0.587, P < 0.001) and PET/CT-reported LN status (AUC, 0.621, P < 0.001) to identify N1 and N2. This signature maintained its independence from clinical risk factors and exhibited robustness in the validation test set. Decision curve analysis attested to the clinical utility of the radiomics signature. CONCLUSIONS: The radiomics signature based on 2-[18F]FDG PET/CT, which derived image features directly from LNs irrespective of clinical risk factors, displayed enhanced diagnostic performance compared to conventional CT or PET/CT-reported LN status. This allows for the identification of pre-surgical LN metastasis status and facilitates a patient-specific prediction of LN metastasis status in CRC patients.