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Revista Da Associacao Medica Brasileira... 2024
Topics: Humans; Tissue Plasminogen Activator; Fibrinolytic Agents; Thrombolytic Therapy; Reperfusion; Recombinant Proteins
PubMed: 38775518
DOI: 10.1590/1806-9282.20240103 -
Heart Views : the Official Journal of... 2024A 40-year-old patient confirmed on computed tomography of the pulmonary arteries (CT/PAs) a large saddle pulmonary embolus in the main PA extending in both branches. He...
A 40-year-old patient confirmed on computed tomography of the pulmonary arteries (CT/PAs) a large saddle pulmonary embolus in the main PA extending in both branches. He was managed by ultrasound-supported catheter-directed (EkoSonic, Boston Scientific) intrapulmonary thrombolytic therapy using a recombinant tissue plasminogen activator prolonged infusion over 16 h with a total dose of 50 mg divided in both PAs simultaneously with intravenous unfractionated heparin. He showed clinical improvement with improved arterial oxygen (PaO2) with reduced oxygen therapy with a nasal cannula. Follow-up right heart catheterization showed a significant reduction of PA pressure from 96/32 (mean 64) to 47/27 (mean 39) mmHg. Repeat pulmonary angiography showed significant improvement in PA branch opacification, suggesting increased flow and successful therapy. The patient received oral anticoagulants for months. He had followed with CT/PA and echocardiogram after 4 weeks, both were normalized. He resumed his regular physical activities, including exercises in the gymnasium.
PubMed: 38774554
DOI: 10.4103/heartviews.heartviews_103_23 -
BMC Ophthalmology May 2024Comparing between the visual outcomes and post operative complications of two surgical treatments for sub macular hemorrhage, pars plana vitrectomy with tissue... (Comparative Study)
Comparative Study
Pneumatic displacement with intravitreal tPA injection versus vitrectomy with sub retinal tPA injection in small and medium sub macular hemorrhages- a multicenter comparative study.
PURPOSE
Comparing between the visual outcomes and post operative complications of two surgical treatments for sub macular hemorrhage, pars plana vitrectomy with tissue plasminogen activator (tPA) injection procedure, and pneumatic displacement of submacular hemorrhage with intravitreal tPA injection.
METHODS
A retrospective chart review of patients with sub macular hemorrhage (SMH) was performed. Data was collected from 150 patients with sub macular hemorrhage. Patients were followed up from the day of admission and up to a year post surgery. Evaluation included visual acuity, optical coherence tomography (OCT), fundus examination and rates of complications.
RESULTS
Pars plana vitrectomy procedure has showed a better visual outcome in small SMH. Comparing complications between the two treatment modalities, no significant difference has been found in the study.
CONCLUSIONS
Pars plana vitrectomy and tPA showed a clear advantage with a trend of better visual acuity as well as a significant predictor to better visual acuity for small and medium sub macular hemorrhage.
Topics: Humans; Tissue Plasminogen Activator; Vitrectomy; Retinal Hemorrhage; Retrospective Studies; Male; Female; Visual Acuity; Intravitreal Injections; Aged; Tomography, Optical Coherence; Fibrinolytic Agents; Middle Aged; Aged, 80 and over
PubMed: 38773500
DOI: 10.1186/s12886-024-03468-9 -
Stroke Jul 2024The dramatic clinical improvement offered by mechanical thrombectomy raised questions about the relevance of prior intravenous thrombolysis in large-vessel occlusion... (Observational Study)
Observational Study
BACKGROUND
The dramatic clinical improvement offered by mechanical thrombectomy raised questions about the relevance of prior intravenous thrombolysis in large-vessel occlusion strokes. Hence, studying intravenous thrombolysis susceptibility and its dependence on thrombus composition is crucial. We used an observational proteomic study of whole thrombi retrieved by mechanical thrombectomy to identify factors associated with fibrin content and fibrinolytic activity (FA).
METHODS
In 104 stroke patients, the thrombi proteome was established by mass spectrometry coupled to liquid chromatography. FA was estimated in clots both outside (FA) by measuring D-dimer levels at the blood-thrombus interface and inside (FA) by evaluating the ratio of fibrinogen α to its plasmin-cleaved forms using proteomics coupled with protein electrophoresis. The factors associated with fibrin content, FA, and FA were determined by intravenous thrombolysis-adjusted linear regression.
RESULTS
FA (<0.0001) and FA (=0.0147) were driven by recombinant tissue-type plasminogen activator (r-tPA) administration (47/104) and thrombus composition. Indeed, FA was greater with fibrin-rich than erythrocyte-rich thrombi, presumably because of more (r)tPA substrates. Thus, FA was increased with cardioembolic thrombi (72/104), which are rich in fibrin (=0.0300). Opposite results were found inside the thrombus, suggesting that (r)tPA penetrability was hampered by the density of the fibrinous cap. Moreover, blood cells had a strong impact on thrombus structure and susceptibility to (r)tPA. Indeed, fibrin content was negatively associated with erythrocyte-specific proteins in the thrombus, admission hematocrit (=0.0139), and hemoglobin level (=0.0080), which underlines the key role of erythrocytes in thrombus composition. Also, an increased number of neutrophils impaired FA (=0.0225), which suggests that their aggregation around the thrombus prevented the (r)tPA attack. Only FA was significantly associated with reduced thrombus weight (=0.0310), increased recanalization rate (=0.0150), good clinical outcome (=0.0480), and reduced mortality (=0.0080).
CONCLUSIONS
Proteomics can offer new insights into the close relationship between thrombus composition and susceptibility to fibrinolysis, paving the way for new adjuvant therapies.
Topics: Humans; Male; Female; Fibrinolysis; Proteomics; Aged; Middle Aged; Intracranial Thrombosis; Stroke; Thrombectomy; Tissue Plasminogen Activator; Fibrin; Aged, 80 and over; Thrombolytic Therapy; Thrombosis
PubMed: 38771990
DOI: 10.1161/STROKEAHA.124.047156 -
Journal of Traditional Chinese Medicine... Jun 2024To investigate the underlying protein molecular mechanisms of " stagnation and blood stasis syndrome" (QS) and " deficiency and blood stasis syndrome" (QD), as two...
Proteomics analysis of coronary atherosclerotic heart disease with different Traditional Chinese Medicine syndrome types before and after percutaneous coronary intervention.
OBJECTIVE
To investigate the underlying protein molecular mechanisms of " stagnation and blood stasis syndrome" (QS) and " deficiency and blood stasis syndrome" (QD), as two subtypes of coronary artery disease (CAD) in Traditional Chinese Medicine (TCM), following percutaneous coronary intervention (PCI).
METHODS
In this study, a total of 227 CAD patients with QS and 211 CAD patients with QD were enrolled; all participants underwent PCI. Label-free quantification proteomics were employed to analyze the changes in serum in two subtypes of CAD patients before and 6 months after PCI, aiming to elucidate the intervention mechanism of PCI in treating CAD characterized by two different TCM syndromes.
RESULTS
Biochemical analysis revealed significant changes in tumor necrosis factor-α, high density lipoprotein cholesterol, blood stasis clinical symptoms observation, and Gensini levels in both patient groups post-PCI; Proteomic analysis identified 79 and 95 differentially expressed proteins in the QS and QD patient groups, respectively, compared to their control groups. complement C8 alpha chain, complement factor H, apolipoprotein H, apolipoprotein B, plasminogen, carbonic anhydrase 2, and complement factor I were altered in both comparison groups. Furthermore, enrichment analysis demonstrated that cell adhesion and connectivity-related processes underwent changes in QS patients post-PCI, whereas lipid metabolism-related pathways, including the peroxisome proliferator-activated receptor signaling pathway and extracellular matrix receptor interaction, underwent changes in the QD group. The protein-protein interaction network analysis further enriched 52 node proteins, including apolipoprotein B, lipoprotein (a), complement C5, apolipoprotein A4, complement C8 alpha chain, complement C8 beta chain, complement C8 gamma chain, apolipoprotein H, apolipoprotein A-Ⅱ, albumin, complement C4-B, apolipoprotein C3, among others. The functional network of these proteins is posited to contribute to the pathophysiology of CAD characterized by TCM syndromes.
CONCLUSION
The current quantitative proteomic study has preliminarily identified biomarkers of CAD in different TCM subtypes treated with PCI, potentially laying the groundwork for understanding the protein profiles associated with the treatment of various TCM subtypes of CAD.
Topics: Humans; Proteomics; Male; Female; Middle Aged; Percutaneous Coronary Intervention; Coronary Artery Disease; Aged; Medicine, Chinese Traditional
PubMed: 38767640
DOI: 10.19852/j.cnki.jtcm.20240408.001 -
Global Heart 2024There is growing evidence that concentrations of DNA methylation are associated with cardiovascular disease; however, it is unclear whether this association reflects a...
BACKGROUND
There is growing evidence that concentrations of DNA methylation are associated with cardiovascular disease; however, it is unclear whether this association reflects a causal relationship.
METHODS
We utilized a two-sample Mendelian randomization (MR) approach to investigate whether DNA methylation can affect the risk of developing cardiovascular disease in human life. We primarily performed the inverse variance weighted (IVW) method to analyze the causal effect of DNA methylation on multiple cardiovascular diseases. Additionally, to ensure the robustness of our findings, we conducted several sensitivity analyses using alternative methodologies. These analysis methods included maximum likelihood, MR-Egger regression, weighted median method, and weighted model methods.
RESULTS
Inverse variance weighted estimates suggested that an SD increase in DNA methylation Hannum age acceleration exposure increased the risk of cardiac arrhythmias (OR = 1.03, 95% CI 1.00-1.05, = 0.0290) and atrial fibrillation (OR = 1.03, 95% CI 1.00-1.05, = 0.0022). We also found that an SD increase in DNA methylation PhenoAge acceleration exposure increased the risk of heart failure (OR = 1.01, 95% CI 1.00-1.03, = 0.0362). Exposure to DNA methylation-estimated granulocyte proportions was found to increase the risk of hypertension (OR = 1.00, 95% CI 1.00-1.0001, p = 0.0291). Exposure to DNA methylation-estimated plasminogen activator inhibitor-1 levels was found to increase the risk of heart failure (OR = 1.00, 95% CI 1.00-1.00, = 0.0215).
CONCLUSION
This study reveals a causal relationship between DNA methylation and CVD. Exposed to high levels of DNA methylation Hannum age acceleration inhabitants with an increased risk of cardiac arrhythmias and atrial fibrillation. DNA methylation PhenoAge acceleration levels exposure levels were positively associated with the increased risk of developing heart failure. This has important implications for the prevention of cardiovascular diseases.
Topics: Humans; DNA Methylation; Mendelian Randomization Analysis; Cardiovascular Diseases; Risk Factors
PubMed: 38765775
DOI: 10.5334/gh.1324 -
PloS One 2024Mechanisms underlying primary and acquired resistance to MET tyrosine kinase inhibitors (TKIs) in managing non-small cell lung cancer remain unclear. In this study, we...
Mechanisms underlying primary and acquired resistance to MET tyrosine kinase inhibitors (TKIs) in managing non-small cell lung cancer remain unclear. In this study, we investigated the possible mechanisms acquired for crizotinib in MET-amplified lung carcinoma cell lines. Two MET-amplified lung cancer cell lines, EBC-1 and H1993, were established for acquired resistance to MET-TKI crizotinib and were functionally elucidated. Genomic and transcriptomic data were used to assess the factors contributing to the resistance mechanism, and the alterations hypothesized to confer resistance were validated. Multiple mechanisms underlie acquired resistance to crizotinib in MET-amplified lung cancer cell lines. In EBC-1-derived resistant cells, the overexpression of SERPINE1, the gene encoding plasminogen activator inhibitor-1 (PAI-1), mediated the drug resistance mechanism. Crizotinib resistance was addressed by combination therapy with a PAI-1 inhibitor and PAI-1 knockdown. Another mechanism of resistance in different subline cells of EBC-1 was evaluated as epithelial-to-mesenchymal transition with the upregulation of antiapoptotic proteins. In H1993-derived resistant cells, MEK inhibitors could be a potential therapeutic strategy for overcoming resistance with downstream mitogen-activated protein kinase pathway activation. In this study, we revealed the different mechanisms of acquired resistance to the MET inhibitor crizotinib with potential therapeutic application in patients with MET-amplified lung carcinoma.
Topics: Humans; Plasminogen Activator Inhibitor 1; Carcinoma, Non-Small-Cell Lung; Drug Resistance, Neoplasm; Proto-Oncogene Proteins c-met; Crizotinib; Lung Neoplasms; Cell Line, Tumor; Protein Kinase Inhibitors; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic
PubMed: 38758826
DOI: 10.1371/journal.pone.0300644 -
Gene Sep 2024Diabetic cardiomyopathy (DCM) is a special type of cardiovascular disease, termed as a situation of abnormal myocardial structure and function that occurs in diabetic...
BACKGROUND
Diabetic cardiomyopathy (DCM) is a special type of cardiovascular disease, termed as a situation of abnormal myocardial structure and function that occurs in diabetic patients. However, the most fundamental mechanisms of DCM have not been fully explicated, and useful targets for the therapeutic strategies still need to be explored.
METHODS
In the present study, we combined bioinformatics analysis and in vitro experiments throughout the process of DCM. Differentially Expressed Genes (DEGs) analysis was performed and the weighted gene co-expression network analysis (WGCNA) was constructed to determine the crucial genes that were tightly connected to DCM. Additionally, Functional enrichment analysis was conducted to define biological pathways. To identify the specific molecular mechanism, the human cardiomyocyte cell line (AC16) was stimulated by high glucose (HG, 50 mM D-glucose) and used to imitate DCM condition. Then, we tentatively examined the effect of high glucose on cardiomyocytes, the expression levels of crucial genes were further validated by in vitro experiments.
RESULTS
Generally, NPPA, IGFBP5, SERPINE1, and C3 emerged as potential therapeutic targets. Functional enrichment analysis performed by bioinformatics indicated that the pathogenesis of DCM is mainly related to heart muscle contraction and calcium (Ca) release activation. In vitro, we discovered that high glucose treatment induced cardiomyocyte injury and exacerbated mitochondrial dysfunction remarkably.
CONCLUSION
Our research defined four crucial genes, as well as determined that mitochondrial function impairment compromises calcium homeostasis ultimately resulting in contractile dysfunction is a central contributor to DCM progression. Hopefully, this study will offer more effective biomarkers for DCM diagnosis and treatment.
Topics: Diabetic Cardiomyopathies; Humans; Myocytes, Cardiac; Glucose; Cell Line; Plasminogen Activator Inhibitor 1; Computational Biology; Gene Regulatory Networks; Gene Expression Profiling; Mitochondria; Calcium
PubMed: 38754569
DOI: 10.1016/j.gene.2024.148563 -
Journal of Atherosclerosis and... May 2024This study investigated the impact of rurality on acute ischemic stroke (AIS) outcomes, emphasizing the hyperacute phase, in which immediate care is crucial.
AIM
This study investigated the impact of rurality on acute ischemic stroke (AIS) outcomes, emphasizing the hyperacute phase, in which immediate care is crucial.
METHODS
This retrospective cohort study analyzed data from a large Japanese hospital network covering AIS patients from 2013-2021, was analyzed. The focus was on patients admitted within 4.5 h of the onset, using the Rurality Index for Japan (RIJ) to categorize patients into rural or urban groups. This study examined treatment methods (intravenous thrombolysis [IVT] and mechanical thrombectomy [MT]) and functional outcomes measured using the modified Rankin Scale (mRS), where scores of 3-6 indicated poor outcomes. Multilevel logistic regression was used to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for poor outcomes baSed on rurality. The study also evaluated the population-attributable fraction (PAF) to estimate potential outcome improvements in urban settings.
RESULTS
Of 27,691 patients, 17,516 were included in the total cohort and 4,954 in the hyperacute cohort. Urban patients constituted 73.7% (12,902), with higher IVT (5.2%) and MT (3.6%) rates than rural patients (4.1% IVT, 2.0% MT). Poor mRS outcomes were more common in rural areas than in urban areas, with adjusted ORs of 1.30 (1.18-1.43) in the total cohort and 1.43 (1.19-1.70) in the hyperacute cohort. The PAF for poor outcomes due to rural residency was 14.8% (0.5%-31.0%).
CONCLUSION
This study demonstrated a notable association between rurality and poorer AIS outcomes in Japan, particularly in the hyperacute phase.
PubMed: 38749742
DOI: 10.5551/jat.64873