RESUMO
The urea cycle (UC) is the main pathway by which mammals dispose of waste nitrogen. We find that specific alterations in the expression of most UC enzymes occur in many tumors, leading to a general metabolic hallmark termed "UC dysregulation" (UCD). UCD elicits nitrogen diversion toward carbamoyl-phosphate synthetase2, aspartate transcarbamylase, and dihydrooratase (CAD) activation and enhances pyrimidine synthesis, resulting in detectable changes in nitrogen metabolites in both patient tumors and their bio-fluids. The accompanying excess of pyrimidine versus purine nucleotides results in a genomic signature consisting of transversion mutations at the DNA, RNA, and protein levels. This mutational bias is associated with increased numbers of hydrophobic tumor antigens and a better response to immune checkpoint inhibitors independent of mutational load. Taken together, our findings demonstrate that UCD is a common feature of tumors that profoundly affects carcinogenesis, mutagenesis, and immunotherapy response.
Assuntos
Genômica , Metabolômica , Neoplasias/patologia , Ureia/metabolismo , Sistemas de Transporte de Aminoácidos Básicos/metabolismo , Animais , Aspartato Carbamoiltransferase/genética , Aspartato Carbamoiltransferase/metabolismo , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)/genética , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)/metabolismo , Linhagem Celular Tumoral , Di-Hidro-Orotase/genética , Di-Hidro-Orotase/metabolismo , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos SCID , Proteínas de Transporte da Membrana Mitocondrial , Neoplasias/metabolismo , Ornitina Carbamoiltransferase/antagonistas & inibidores , Ornitina Carbamoiltransferase/genética , Ornitina Carbamoiltransferase/metabolismo , Fosforilação/efeitos dos fármacos , Pirimidinas/biossíntese , Pirimidinas/química , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/antagonistas & inibidores , Serina-Treonina Quinases TOR/metabolismoRESUMO
Molecular motors employ chemical energy to generate unidirectional mechanical output against a track while navigating a chaotic cellular environment, potential disorder on the track, and against Brownian motion. Nevertheless, decades of nanometer-precise optical studies suggest that myosin-5a, one of the prototypical molecular motors, takes uniform steps spanning 13 subunits (36 nm) along its F-actin track. Here, we use high-resolution interferometric scattering microscopy to reveal that myosin takes strides spanning 22 to 34 actin subunits, despite walking straight along the helical actin filament. We show that cumulative angular disorder in F-actin accounts for the observed proportion of each stride length, akin to crossing a river on variably spaced stepping stones. Electron microscopy revealed the structure of the stepping molecule. Our results indicate that both motor and track are soft materials that can adapt to function in complex cellular conditions.
Assuntos
Actinas , Miosina Tipo V , Actinas/química , Miosinas/química , Citoesqueleto de Actina/química , Movimento (Física) , Miosina Tipo V/químicaRESUMO
Aging is associated with increased mutational burden in every tissue studied. Occasionally, fitness-increasing mutations will arise, leading to stem cell clonal expansion. This process occurs in several tissues but has been best studied in blood. Clonal hematopoiesis is associated with an increased risk of blood cancers, such as acute myeloid leukemia, which result if additional cooperating mutations occur. Surprisingly, it is also associated with an increased risk of nonmalignant diseases, such as atherosclerotic cardiovascular disease. This may be due to enhanced inflammation in mutated innate immune cells, which could be targeted clinically with anti-inflammatory drugs. Recent studies have uncovered other factors that predict poor outcomes in patients with clonal hematopoiesis, such as size of the mutant clone, mutated driver genes, and epigenetic aging. Though clonality is inevitable and largely a function of time, recent work has shown that inherited genetic variation can also influence this process. Clonal hematopoiesis provides a paradigm for understanding how age-related changes in tissue stem cell composition and function influence human health.
Assuntos
Neoplasias Hematológicas , Lesões Pré-Cancerosas , Humanos , Hematopoiese Clonal/genética , Hematopoese/genética , Neoplasias Hematológicas/genética , Envelhecimento/genética , Lesões Pré-Cancerosas/patologia , Mutação/genéticaRESUMO
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolves rapidly under the pressure of host immunity, as evidenced by waves of emerging variants despite effective vaccinations, highlighting the need for complementing antivirals. We report that targeting a pyrimidine synthesis enzyme restores inflammatory response and depletes the nucleotide pool to impede SARS-CoV-2 infection. SARS-CoV-2 deploys Nsp9 to activate carbamoyl-phosphate synthetase, aspartate transcarbamoylase, and dihydroorotase (CAD) that catalyzes the rate-limiting steps of the de novo pyrimidine synthesis. Activated CAD not only fuels de novo nucleotide synthesis but also deamidates RelA. While RelA deamidation shuts down NF-κB activation and subsequent inflammatory response, it up-regulates key glycolytic enzymes to promote aerobic glycolysis that provides metabolites for de novo nucleotide synthesis. A newly synthesized small-molecule inhibitor of CAD restores antiviral inflammatory response and depletes the pyrimidine pool, thus effectively impeding SARS-CoV-2 replication. Targeting an essential cellular metabolic enzyme thus offers an antiviral strategy that would be more refractory to SARS-CoV-2 genetic changes.
Assuntos
Antivirais , Aspartato Carbamoiltransferase , Tratamento Farmacológico da COVID-19 , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante) , Di-Hidro-Orotase , Inibidores Enzimáticos , Pirimidinas , SARS-CoV-2 , Replicação Viral , Animais , Antivirais/farmacologia , Antivirais/uso terapêutico , Aspartato Carbamoiltransferase/antagonistas & inibidores , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)/antagonistas & inibidores , Di-Hidro-Orotase/antagonistas & inibidores , Ativação Enzimática/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Humanos , Inflamação/tratamento farmacológico , Camundongos , Pirimidinas/antagonistas & inibidores , Pirimidinas/biossíntese , Proteínas de Ligação a RNA/metabolismo , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/fisiologia , Fator de Transcrição RelA/metabolismo , Proteínas não Estruturais Virais/metabolismo , Replicação Viral/efeitos dos fármacosRESUMO
CTNNB1, encoding ß-catenin protein, is the most frequently altered proto-oncogene in hepatic neoplasms. In this study, we studied the significance and pathological mechanism of CTNNB1 gain-of-function mutations in hepatocarcinogenesis. Activated ß-catenin not only triggered hepatic tumorigenesis but also exacerbated Tp53 deletion or hepatitis B virus infection-mediated liver cancer development in mouse models. Using untargeted metabolomic profiling, we identified boosted de novo pyrimidine synthesis as the major metabolic aberration in ß-catenin mutant cell lines and livers. Oncogenic ß-catenin transcriptionally stimulated AKT2, which then phosphorylated the rate-limiting de novo pyrimidine synthesis enzyme CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, dihydroorotase) on S1406 and S1859 to potentiate nucleotide synthesis. Moreover, inhibition of ß-catenin/AKT2-stimulated pyrimidine synthesis axis preferentially repressed ß-catenin mutant cell proliferation and tumor formation. Therefore, ß-catenin active mutations are oncogenic in various preclinical liver cancer models. Stimulation of ß-catenin/AKT2/CAD signaling cascade on pyrimidine synthesis is an essential and druggable vulnerability for ß-catenin mutant liver cancer.
Assuntos
Neoplasias Hepáticas , Pirimidinas , beta Catenina , Animais , Ácido Aspártico , Carcinogênese , Di-Hidro-Orotase/genética , Di-Hidro-Orotase/metabolismo , Sistemas de Liberação de Medicamentos , Ligases , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/fisiopatologia , Camundongos , Nucleotídeos , Fosfatos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirimidinas/biossíntese , beta Catenina/metabolismoRESUMO
Despite inflammation being implicated in cardiovascular disease (CVD) in people with HIV (PWH), considerable heterogeneity within populations of PWH exists. Stratifying CVD risk based on inflammatory phenotype could play an important role. Using principal component analyses and unsupervised hierarchical clustering, we examined 38 biomarkers to identify inflammatory phenotypes in two independent cohorts of PWH. We identified three distinct inflammatory clusters present in both cohorts that associated with altered risk of both subclinical CVD (cohort 1) and prevalent clinical CVD (cohort 2) after adjusting for CVD risk factors. These data support precision medicine approaches to enhance CVD risk assessment in PWH.
RESUMO
During coronary artery bypass grafting (CABG), the surgical procedure, particularly the manipulation of the major arteries of the heart, induces a significant inflammatory state that may compromise platelet function to the extent that platelet transfusion is required. Given stored platelets as a major source of biological mediators, this study investigates the effects of platelet transfusion on the major pro-aggregatory, pro-inflammatory and immunomodulatory markers of platelets. Platelets from 20 patients, 10 who received platelet transfusion and 10 without, were subjected to flow cytometery where P-selectin and CD40 ligand (CD40L) expressions and PAC-1 binding (activation-specific anti GPIIb/GPIIIa antibody) analysed at five-time points of 24 h before surgery, immediately, 2 h, 24 h and 1 week after surgery. Analysis of intra-platelet transforming growth factor-beta-1 (TGF-ß1) was also conducted using western blotting. Patients with platelet transfusion showed increased levels of P-selectin, CD40L and intra-platelet TGF-ß1 2-h after surgery compared to those without transfusion (p < 0.05). PAC-1 binding was increased 24 h after surgery in transfused patients (p < 0.05). Given the significant post-transfusion elevation of platelet TGF-ß1, P-sel/CD40L reduction in transfused patients a week after was of much interest. This study showed for the first time the significant effects of platelet transfusion on the pro-inflammatory, pro-aggeregatory and immunomodulatory state of platelets in CABG patients, which manifested with immediate, midterm and delayed consequences. While the increased pro-inflammatory conditions manifested as an immediate effect of platelet transfusion, the pro-aggregatory circumstances emerged 24 h post-transfusion. A week after surgery, attenuations of pro-inflammatory markers of platelets in transfused patients were shown, which might be due to the immunomodulatory effects of TGF-ß1.
Assuntos
Plaquetas , Ligante de CD40 , Ponte de Artéria Coronária , Selectina-P , Transfusão de Plaquetas , Humanos , Ponte de Artéria Coronária/efeitos adversos , Plaquetas/metabolismo , Masculino , Feminino , Selectina-P/sangue , Selectina-P/metabolismo , Pessoa de Meia-Idade , Ligante de CD40/sangue , Ligante de CD40/metabolismo , Idoso , Fator de Crescimento Transformador beta1/sangue , Fator de Crescimento Transformador beta1/metabolismo , Inflamação/sangue , Agregação PlaquetáriaRESUMO
BACKGROUND: CINNAMYL ALCOHOL DEHYDROGENASE (CAD) catalyzes the NADPH-dependent reduction of cinnamaldehydes into cinnamyl alcohols and is a key enzyme found at the final step of the monolignol pathway. Cinnamyl alcohols and their conjugates are subsequently polymerized in the secondary cell wall to form lignin. CAD genes are typically encoded by multi-gene families and thus traditionally organized into general classifications of functional relevance. RESULTS: In silico analysis of the hexaploid Triticum aestivum genome revealed 47 high confidence TaCAD copies, of which three were determined to be the most significant isoforms (class I) considered bone fide CADs. Class I CADs were expressed throughout development both in RNAseq data sets as well as via qRT-PCR analysis. Of the 37 class II TaCADs identified, two groups were observed to be significantly co-expressed with class I TaCADs in developing tissue and under chitin elicitation in RNAseq data sets. These co-expressed class II TaCADs were also found to be phylogenetically unrelated to a separate clade of class II TaCADs previously reported to be an influential resistance factor to pathogenic fungal infection. Lastly, two groups were phylogenetically identified as class III TaCADs, which possess distinct conserved gene structures. However, the lack of data supporting their catalytic activity for cinnamaldehydes and their bereft transcriptional presence in lignifying tissues challenges their designation and function as CADs. CONCLUSIONS: Taken together, our comprehensive transcriptomic analyses suggest that TaCAD genes contribute to overlapping but nonredundant functions during T. aestivum growth and development across a wide variety of agroecosystems and provide tolerance to various stressors.
Assuntos
Oxirredutases do Álcool , Regulação da Expressão Gênica de Plantas , Família Multigênica , Filogenia , Triticum , Triticum/genética , Triticum/enzimologia , Oxirredutases do Álcool/genética , Oxirredutases do Álcool/metabolismo , Perfilação da Expressão Gênica , Genoma de Planta , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Coronary heart disease is one of the most significant risk factors affecting human health worldwide. Its pathogenesis is intricate, with atherosclerosis being widely regarded as the leading cause. Aberrant lipid metabolism in macrophages is recognized as one of the triggering factors in atherosclerosis development. To investigate the role of macrophages in the formation of coronary artery atherosclerosis, we utilized single-cell data from wild-type mice obtained from the aortic roots and ascending aortas after long-term high-fat diet feeding, as deposited in GSE131776. Seurat software was employed to refine the single-cell data in terms of scale and cell types, facilitating the identification of differentially expressed genes. Through the application of differential expression genes, we conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses at 0, 8 and 16 weeks, aiming to uncover pathways with the most pronounced functional alterations as the high-fat diet progressed. The AddModuleScore function was employed to score the expression of these pathways across different cell types. Subsequently, macrophages were isolated and further subdivided into subtypes, followed by an investigation into intercellular communication within these subtypes. Subsequent to this, we induced THP-1 cells to generate foam cells, validating critical genes identified in prior studies. The results revealed that macrophages underwent the most substantial functional changes as the high-fat diet progressed. Furthermore, two clusters were identified as potentially playing pivotal roles in macrophage functional regulation during high-fat diet progression. Additionally, macrophage subtypes displayed intricate functionalities, with mutual functional counterbalances observed among these subtypes. The proportions of macrophage subtypes and the modulation of anti-inflammatory and pro-inflammatory functions played significant roles in the development of coronary artery atherosclerosis.
Assuntos
Aterosclerose , Doença da Artéria Coronariana , Humanos , Camundongos , Animais , Doença da Artéria Coronariana/genética , Macrófagos/metabolismo , Macrófagos/patologia , Aterosclerose/genética , Células Espumosas/metabolismo , Células Espumosas/patologiaRESUMO
Foot-and-mouth disease virus (FMDV) is a single-stranded picornavirus that causes economically devastating disease in even-hooved animals. There has been little research on the function of host cells during FMDV infection. We aimed to shed light on key host factors associated with FMDV replication during acute infection. We found that HDAC1 overexpression in host cells induced upregulation of FMDV RNA and protein levels. Activation of the AKT-mammalian target of rapamycin (mTOR) signaling pathway using bpV(HOpic) or SC79 also promoted FMDV replication. Furthermore, short hairpin RNA (shRNA)-induced suppression of carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD), a transcription factor downstream of the AKT-mTOR signaling pathway, resulted in downregulation of FMDV RNA and protein levels. Coimmunoprecipitation assays showed that the ACTase domain of CAD could interact with the FMDV 2C protein, suggesting that the ACTase domain of CAD may be critical in FMDV replication. CAD proteins participate in de novo pyrimidine synthesis. Inhibition of FMDV replication by deletion of the ACTase domain of CAD in host cells could be reversed by supplementation with uracil. These results revealed that the contribution of the CAD ACTase domain to FMDV replication is dependent on de novo pyrimidine synthesis. Our research shows that HDAC1 promotes FMDV replication by regulating de novo pyrimidine synthesis from CAD via the AKT-mTOR signaling pathway. IMPORTANCE Foot-and-mouth disease virus is an animal virus of the Picornaviridae family that seriously harms the development of animal husbandry and foreign trade of related products, and there is still a lack of effective means to control its harm. Replication complexes would generate during FMDV replication to ensure efficient replication cycles. 2C is a common viral protein in the replication complex of Picornaviridae virus, which is thought to be an essential component of membrane rearrangement and viral replication complex formation. The host protein CAD is a key protein in the pyrimidines de novo synthesis. In our research, the interaction of CAD and FMDV 2C was demonstrated in FMDV-infected BHK-21 cells, and it colocalized with 2C in the replication complex. The inhibition of the expression of FMDV 3D protein through interference with CAD and supplementation with exogenous pyrimidines reversed this inhibition, suggesting that FMDV might recruit CAD through the 2C protein to ensure pyrimidine supply during replication. In addition, we also found that FMDV infection decreased the expression of the host protein HDAC1 and ultimately inhibited CAD activity through the AKT-mTOR signaling pathway. These results revealed a unique means of counteracting the virus in BHK-21 cells lacking the interferon (IFN) signaling pathway. In conclusion, our study provides some potential targets for the development of drugs against FMDV.
Assuntos
Vírus da Febre Aftosa , Febre Aftosa , Animais , Linhagem Celular , Vírus da Febre Aftosa/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pirimidinas , RNA/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Replicação Viral , CricetinaeRESUMO
BACKGROUND: Atherogenic index of plasma (AIP) represents a novel marker in the current era of cardiovascular diseases. In this meta-analysis, we aimed to evaluate the association of AIP with cardiovascular prognosis in patients with coronary artery disease (CAD). METHODS: PubMed, Scopus, and Web of Science databases were searched from inception through 2024. The primary outcome was major cardiovascular events (MACE). The secondary outcomes included all-causes death, cardiovascular death, myocardial infarction (MI), stroke, revascularization, and no-reflow phenomenon. AIP was determined by taking the logarithm of the ratio of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C). The data analysis was represented using the risk ratio (RR) along with a 95% confidence interval (CI). RESULTS: Sixteen studies with a total number of 20,833 patients met the eligible criteria. The pooled-analysis showed a significant increased risk of MACE in the highest AIP group compared with the lowest AIP group (RR = 1.63; 95% CI, 1.44-1.85; P < 0.001). A similar result was observed when AIP was regarded as a continuous variable (RR = 1.54; 95% CI, 1.30-1.83; P < 0.001). Besides, elevated AIP was associated with increased risk of cardiovascular death (RR = 1.79; 95% CI, 1.09-2.78; P = 0.02), MI (RR = 2.21; 95% CI, 1.55-3.13; P < 0.001), revascularization (RR = 1.62; 95% CI, 1.34-1.97; P < 0.001), no-reflow phenomenon (RR = 3.12 95% CI, 1.09-8.96; P = 0.034), and stent thrombosis (RR = 13.46; 95%CI, 1.39-129.02; P = 0.025). However, AIP was not significantly associated with the risk of all-causes death and stroke among patients with CAD. CONCLUSIONS: The results of this study demonstrated that increased AIP is an independent prognostic factors in patients with CAD. Further research is warranted to elucidate the potential development of targeted interventions to modify AIP levels and improve patient outcomes.
Assuntos
Biomarcadores , Doença da Artéria Coronariana , Valor Preditivo dos Testes , Humanos , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/terapia , Medição de Risco , Biomarcadores/sangue , Prognóstico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Triglicerídeos/sangue , HDL-Colesterol/sangue , Causas de Morte , Fatores de TempoRESUMO
BACKGROUND: Coronary artery bypass grafting (CABG) is considered the choice treatment for patients suffering from coronary artery disease (CAD). In the inflammatory milieu of cardiopulmonary bypass (CPB), systemic inflammatory response syndrome (SIRS) can induce a platelet pro-inflammatory state which could exacerbate post-CABG inflammatory status while affecting hemostatic function in patients. Therefore, focusing on platelets, the study presented here attempted to evaluate the pro-inflammatory and immunomodulatory profile of platelets as well as pro-aggregatory status during CABG. METHODS: Platelets from patients undergoing CABG were subjected to flowcytometry analysis to evaluate P-selectin and CD40L expressions and PAC-1 binding in five intervals of 24 h before surgery, immediately, 2 h, 24 h, and one week after surgery. Moreover, intra-platelet TGF-ß1 was also examined with western blotting. RESULTS: Data showed increases of P-selectin and CD40L expressions in patients, with the meaningful loss of platelet contents of TGF-ß1 after CABG (p < 0.001), where the changes tended to recover by day 7 of surgery while remaining above baseline (p < 0.001). Meanwhile, no significant change in PAC-1 binding capacity was shown. CONCLUSION: The study presented here suggests that although the release of pro-inflammatory substances from platelets during CABG supports the post-operative inflammatory state, platelets are not pro-aggregatory enough to enhance thrombotic events after surgery. Whilst these observations could be due to successful medical interventions to optimize hemostasis during and after surgery, post-CABG reversal of anticoagulant by protamine is considered as another factor that may also have contributed to preventing pro-aggregatory but not pro-inflammatory and immunomodulatory functions of platelets.
Assuntos
Selectina-P , Fator de Crescimento Transformador beta1 , Humanos , Fator de Crescimento Transformador beta1/metabolismo , Selectina-P/metabolismo , Ligante de CD40 , Ponte de Artéria Coronária/efeitos adversos , Fenótipo , Plaquetas/metabolismoRESUMO
Background: The correlation between 5 ' -Nucleotidase ( 5 ' -NT) and the clinical outcomes in coronary artery disease (CAD) patients following percutaneous coronary intervention (PCI) is not clear. This study aims to clarify this relationship. Methods: The PRACTICE study enrolled 15,250 patients between December 2016 and October 2021. After filtering out those without 5 ' -NT data, a total of 6555 patients were analyzed with a median follow-up of 24 months. Based on the receiver operating characteristic (ROC) curve analysis, a 5 ' -NT level of 5.57 U/L was selected as the optimal cutoff value. All research samples were divided into high-value ( ≥ 5.57 U/L, n = 2346) and low-value groups ( < 5.57 U/L, n = 4209). Key clinical outcomes included all-cause death (ACD), cardiovascular death (CD), major adverse cardiovascular events (MACE), and major adverse cardiovascular and cerebrovascular events (MACCE). After separating patients into high and low value groups, multivariate Cox regression analysis was used to correct for potential confounding variables. Finally, risk ratios and their 95% confidence intervals (CIs) were calculated. Results: During the follow-up period, 129 instances of ACD were recorded-49 cases (1.2%) in the low-value group and 80 cases (3.4%) in the high-value group. Similarly, 102 CDs occurred, including 42 low-value group cases (1.0%) and 60 high-value group cases (2.6%). A total of 363 MACE occurred, including 198 low-value group cases (4.7%) and 165 high-value group cases (7%). A total of 397 cases of MACCE occurred, including 227 low-value group cases (5.4%) and 170 high-value group cases (7.2%). As serum 5 ' -NT increased, the incidence of ACD, CD, MACE and MACCE increased. After multivariate Cox regression, high 5 ' -NT levels were linked with a 1.63-fold increase in ACD risk (hazard ratio [HR] = 2.630, 95% CI: [1.770-3.908], p < 0.001) when compared to low 5 ' -NT patients. Similarly, the risk of CD, MACE, and MACCE increased by 1.298-fold (HR = 2.298, 95% CI: [1.477-3.573], p < 0.001), 41% (HR = 1.410, 95% CI: [1.124-1.768], p = 0.003) and 30.5% (HR = 1.305, 95% CI: [1.049-1.623], p = 0.017), respectively. Conclusions: high serum 5 ' -NT levels were independently correlated with adverse clinical outcomes in CAD patients following PCI, affirming its potential as a prognostic indicator.
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Catheter kinking is not an uncommon scenario during cardiac catheterization via transradial access in patients with tortuous vascular anatomy. Several noninvasive and invasive methods have been described to unkink and retrieve the kinked catheter out of the vessel. We present a novel mother-daughter technique to retrieve a kinked radial artery catheter.
Assuntos
Mães , Artéria Radial , Feminino , Humanos , Artéria Radial/diagnóstico por imagem , Núcleo Familiar , Angiografia Coronária , Resultado do Tratamento , Catéteres , Cateterismo Cardíaco/métodosRESUMO
BACKGROUND: The J-chronic total occlusion (CTO) channel score can predict guidewire tracking of the collateral channels (CCs), but its efficacy in predicting microcatheter tracking has never been tested in the setting of retrograde CTO-percutaneous coronary intervention (PCI). AIMS: Predicting microcatheter collateral tracking during retrograde CTO-PCIs. METHODS: A total of 189 patients undergoing retrograde CTO-PCI from April 2017 to August 2021 were screened. The primary outcome of interest was a correlation between J-CTO channel score and microcatheter tracking failure (MTF) after successful CC tracking by the guidewire. The independent association between anatomical features of the J-CTO channel score and the primary outcome of interest was explored. RESULTS: After adjustment, only small size (adjusted OR: 12.70, 95% confidence interval [CI]: 1.79-89.82; p = 0.01) and continuous bends (adjusted OR: 14.15, 95% CI: 2.77-72.34; p < 0.001) remained significantly associated with an increased risk of MTF for septal collaterals. The small size was the only predictor of the MTF for epicardial collaterals (OR: 6.39, 95% CI: 1.13-35.96; p = 0.020) at univariate analysis. Patients in the MTF group had a lower incidence of procedural success compared with patients in the microcatheter tracking success (MTS) group (40.0% vs. 93.9%, p < 0.001) and had a higher incidence of collateral perforations (20.0% vs. 3.0%, p < 0.001). CONCLUSION: Small and tortuous septal collaterals, identified by a score ≥3, are associated with an increased risk of MTF, lower incidence of procedural success, and higher risk of procedural complications driven by collateral perforations.
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Oclusão Coronária , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Resultado do Tratamento , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/terapia , Oclusão Coronária/etiologia , Angiografia Coronária , Doença Crônica , Circulação Colateral , Sistema de Registros , Fatores de RiscoRESUMO
BACKGROUND: Double kissing crush (DKC) and nano-crush (NC) techniques are frequently used, but the comparison for both techniques is still lacking. The goal of this multicenter study was to retrospectively assess the midterm clinical results of DKC and NC stenting in patients with complex bifurcation lesions (CBLs). METHODS: A total of 324 consecutive patients [male: 245 (75.6%), mean age: 60.73 ± 10.21 years] who underwent bifurcation percutaneous coronary intervention between January 2019 and May 2023 were included. The primary endpoint defined as the major cardiovascular events (MACE) included cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target lesion revascularization (TLR). Inverse probability weighting (IPW) was performed to reduce treatment selection bias. This is the first report comparing the clinical outcomes of DKC and NC stenting in patients with CBL. RESULTS: The initial revascularization strategy was DKC in 216 (66.7%) cases and NC in 108 (33.3%) patients. SYNTAX scores [25.5 ± 6.73 vs. 23.32 ± 6.22, p = 0.005] were notably higher in the NC group than the DKC group. The procedure time (76.98 ± 25.1 vs. 57.5 ± 22.99 min, p = 0.001) was notably higher in the DKC group. The incidence of MACE (18.5 vs. 9.7%, p = 0.025), clinically driven TLR (14.8 vs. 6%, p = 0.009), and TVMI (10.2 vs. 4.2%, p = 0.048) were notably higher in the NC group than in the DKC group. The midterm MACE rate in the overall population notably differed between the NC group and the DKC group (adjusted HR (IPW): 2.712, [95% CI: 1.407-5.228], p = 0.003). CONCLUSION: In patients with CBLs, applying the DKC technique for bifurcation treatment had better ischemia-driven outcomes than the NC technique.
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Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Fatores de Tempo , Fatores de Risco , Intervenção Coronária Percutânea/instrumentação , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Stents , Medição de Risco , Stents FarmacológicosRESUMO
BACKGROUND: The optimal cardiovascular assessment of liver transplant (LT) candidates is unclear. We aimed to evaluate the performance of CT-based coronary tests (coronary artery calcium score [CACS] and coronary CT angiography [CCTA]) and a modification of the CAD-LT score (mCAD-LT, excluding family history of CAD) to diagnose significant coronary artery disease (CAD) before LT and predict the incidence of post-LT cardiovascular events (CVE). METHODS: We retrospectively analysed a single-centre cohort of LT candidates who underwent non-invasive tests; invasive coronary angiography (ICA) was performed depending on the results of non-invasive tests. mCAD-LT was calculated in all patients. RESULTS: Six-hundred-and-thirty-four LT candidates were assessed and 351 of them underwent LT. CACS, CCTA and ICA were performed in 245, 123 and 120 LT candidates, respectively. Significant CAD was found in 30% of patients undergoing ICA. The AUROCs of mCAD-LT (.722) and CCTA (.654) were significantly higher than that of CACS (.502) to predict the presence of significant CAD. Specificity of the tests ranged between 31% for CCTA and 53% for CACS. Among patients who underwent LT, CACS ≥ 400 and mCAD-LT were independently associated with the incidence of CVE; in patients who underwent CCTA before LT, significant CAD at CCTA also predicted post-LT CVE. CONCLUSION: In this cohort, mCAD-LT score and CT-based tests detect the presence of significant CAD in LT candidates, although they tend to overestimate it. Both mCAD-LT score and CT-based tests classify LT recipients according to their risk of post-LT CVE and can be used to improve post-LT risk mitigation.
Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana , Transplante de Fígado , Humanos , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Transplante de Fígado/efeitos adversos , Medição de Risco , Idoso , Valor Preditivo dos Testes , Calcificação Vascular/diagnóstico por imagem , Adulto , Fatores de RiscoRESUMO
BACKGROUND: We developed an explainable deep-learning (DL)-based classifier to identify flow-limiting coronary artery disease (CAD) by O-15 H2O perfusion positron emission tomography computed tomography (PET/CT) and coronary CT angiography (CTA) imaging. The classifier uses polar map images with numerical data and visualizes data findings. METHODS: A DLmodel was implemented and evaluated on 138 individuals, consisting of a combined image-and data-based classifier considering 35 clinical, CTA, and PET variables. Data from invasive coronary angiography were used as reference. Performance was evaluated with clinical classification using accuracy (ACC), area under the receiver operating characteristic curve (AUC), F1 score (F1S), sensitivity (SEN), specificity (SPE), precision (PRE), net benefit, and Cohen's Kappa. Statistical testing was conducted using McNemar's test. RESULTS: The DL model had a median ACC = 0.8478, AUC = 0.8481, F1S = 0.8293, SEN = 0.8500, SPE = 0.8846, and PRE = 0.8500. Improved detection of true-positive and false-negative cases, increased net benefit in thresholds up to 34%, and comparable Cohen's kappa was seen, reaching similar performance to clinical reading. Statistical testing revealed no significant differences between DL model and clinical reading. CONCLUSIONS: The combined DL model is a feasible and an effective method in detection of CAD, allowing to highlight important data findings individually in interpretable manner.
Assuntos
Doença da Artéria Coronariana , Aprendizado Profundo , Radioisótopos de Oxigênio , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/diagnóstico por imagem , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Imagem de Perfusão do Miocárdio/métodos , Angiografia por Tomografia Computadorizada/métodos , Isquemia Miocárdica/diagnóstico por imagem , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To elucidate the value of gated SPECT-MPI using CT attenuation correction (AC) for prediction of pulmonary hypertension (PHT) in coronary patients by estimation of reliability of non-contrast CT in measurement of main pulmonary artery diameter (MPAd) as well as by assessment of potential predictive role of gated parameters as beneficial accessory findings. BACKGROUND: Contrast-enhanced CT is known as an accurate tool for assessment of MPAd to predict PHT. [1] The low-dose non-contrast CT which is used for AC in MPI study, however, has an unclear value in precise vascular diameter measurement; it is also uncertain whether gated parameters could help to predict PHT. METHODS AND PATIENTS: A total of 207 patients, who had a transthoracic echocardiography and MPI with an interval of maximum one month, underwent this retrospective study. PHT was defined as a RVSP ≥36 mmHg by echocardiography; peak tricuspid regurgitation velocity (PTRV) was also calculated to use as a criterion for PHT. Of all subjects, 120 had RVSP ≥ 36 and 87 showed RVSP < 36; there also were 191 and 16 patients with PTRV ≤ 3.4 m/s and >3.4 m/s, respectively. Comparison was made unconnectedly between each group regarding the echocardiography results with the MPI parameters, with and without CT-AC, including MPAd derived from CT as well as RV/LV uptake ratio, shape index and septal wall motion and thickening scores to define the best indicators of PHT. RESULTS: There was a significant association between established benchmark of PHT in echocardiography (RVSP), with MPAd derived from non-contrast CT as well as with LV shape index from gated study and RV/LV uptake ratio acquired from non-AC SPECT-MPI. Also, stress and rest RV/LV uptake ratio, MPAd, LV end-systolic and LV end-diastolic shape indexes are significantly higher in patients with RVSP ≥ 36 mmHg compare to patients with RVSP < 36 mmHg. CONCLUSIONS: Gated-SPECT-MPI using CT-AC can predict PHT by reliable estimation of MPAd as well as by defining RV/LV uptake ratio and shape index, providing an added clinical value for this invaluable modality in cardiac patients.
Assuntos
Hipertensão Pulmonar , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Estudos Retrospectivos , Reprodutibilidade dos Testes , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
OBJECTIVES: Recently, artificial intelligence (AI) has been applied to clinical diagnosis. Although AI has already been developed for gastrointestinal (GI) tract endoscopy, few studies have applied AI to endoscopic ultrasound (EUS) images. In this study, we used a computer-assisted diagnosis (CAD) system with deep learning analysis of EUS images (EUS-CAD) and assessed its ability to differentiate GI stromal tumors (GISTs) from other mesenchymal tumors and their risk classification performance. MATERIALS AND METHODS: A total of 101 pathologically confirmed cases of subepithelial lesions (SELs) arising from the muscularis propria layer, including 69 GISTs, 17 leiomyomas and 15 schwannomas, were examined. A total of 3283 EUS images were used for training and five-fold-cross-validation, and 827 images were independently tested for diagnosing GISTs. For the risk classification of 69 GISTs, including very-low-, low-, intermediate- and high-risk GISTs, 2,784 EUS images were used for training and three-fold-cross-validation. RESULTS: For the differential diagnostic performance of GIST among all SELs, the accuracy, sensitivity, specificity and area under the receiver operating characteristic (ROC) curve were 80.4%, 82.9%, 75.3% and 0.865, respectively, whereas those for intermediate- and high-risk GISTs were 71.8%, 70.2%, 72.0% and 0.771, respectively. CONCLUSIONS: The EUS-CAD system showed a good diagnostic yield in differentiating GISTs from other mesenchymal tumors and successfully demonstrated the GIST risk classification feasibility. This system can determine whether treatment is necessary based on EUS imaging alone without the need for additional invasive examinations.