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1.
Atherosclerosis ; 340: 12-22, 2022 01.
Article in English | MEDLINE | ID: covidwho-1536439

ABSTRACT

BACKGROUND AND AIMS: The atherosclerotic plaque microenvironment is highly complex, and selective agents that modulate plaque stability are not yet available. We sought to develop a scRNA-seq analysis workflow to investigate this environment and uncover potential therapeutic approaches. We designed a user-friendly, reproducible workflow that will be applicable to other disease-specific scRNA-seq datasets. METHODS: Here we incorporated automated cell labeling, pseudotemporal ordering, ligand-receptor evaluation, and drug-gene interaction analysis into a ready-to-deploy workflow. We applied this pipeline to further investigate a previously published human coronary single-cell dataset by Wirka et al. Notably, we developed an interactive web application to enable further exploration and analysis of this and other cardiovascular single-cell datasets. RESULTS: We revealed distinct derivations of fibroblast-like cells from smooth muscle cells (SMCs), and showed the key changes in gene expression along their de-differentiation path. We highlighted several key ligand-receptor interactions within the atherosclerotic environment through functional expression profiling and revealed several avenues for future pharmacological development for precision medicine. Further, our interactive web application, PlaqView (www.plaqview.com), allows lay scientists to explore this and other datasets and compare scRNA-seq tools without prior coding knowledge. CONCLUSIONS: This publicly available workflow and application will allow for more systematic and user-friendly analysis of scRNA datasets in other disease and developmental systems. Our analysis pipeline provides many hypothesis-generating tools to unravel the etiology of coronary artery disease. We also highlight potential mechanisms for several drugs in the atherosclerotic cellular environment. Future releases of PlaqView will feature more scRNA-seq and scATAC-seq atherosclerosis-related datasets to provide a critical resource for the field, and to promote data harmonization and biological interpretation.


Subject(s)
Coronary Artery Disease , Pharmaceutical Preparations , Coronary Artery Disease/drug therapy , Coronary Artery Disease/genetics , Gene Expression Profiling , Humans , RNA-Seq , Sequence Analysis, RNA , Single-Cell Analysis , Software , Workflow
2.
J Fam Pract ; 70(8): 403-407, 2021 10.
Article in English | MEDLINE | ID: covidwho-1485519

ABSTRACT

A meta-analysis found oral anticoagulant (OAC) monotherapy provided efficacy comparable to OAC plus single antiplatelet therapy-with lower bleeding risk.


Subject(s)
Atrial Fibrillation/drug therapy , Coronary Artery Disease/complications , Factor Xa Inhibitors/pharmacology , Coronary Artery Disease/drug therapy , Factor Xa Inhibitors/standards , Humans , Risk Factors , Treatment Outcome
4.
J Med Virol ; 93(9): 5390-5395, 2021 09.
Article in English | MEDLINE | ID: covidwho-1363677

ABSTRACT

Hypercoagulability and thrombosis caused by coronavirus disease 2019 (COVID-19) are related to the higher mortality rate. Because of limited data on the antiplatelet effect, we aimed to evaluate the impact of aspirin add-on therapy on the outcome of the patients hospitalized due to severe COVID-19. In this cohort study, patients with a confirmed diagnosis of severe COVID-19 admitted to Imam Hossein Medical Center, Tehran, Iran from March 2019 to July 2020 were included. Demographics and related clinical data during their hospitalization were recorded. The mortality rate of the patients was considered as the primary outcome and its association with aspirin use was assessed. Nine hundred and ninety-one patients were included, of that 336 patients (34%) received aspirin during their hospitalization and 655 ones (66%) did not. Comorbidities were more prevalent in the patients who were receiving aspirin. Results from the multivariate COX proportional model demonstrated a significant independent association between aspirin use and reduction in the risk of in-hospital mortality (0.746 [0.560-0.994], p = 0.046). Aspirin use in hospitalized patients with COVID-19 is associated with a significant decrease in mortality rate. Further prospective randomized controlled trials are needed to assess the efficacy and adverse effects of aspirin administration in this population.


Subject(s)
Aspirin/therapeutic use , COVID-19/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Pulmonary Embolism/drug therapy , SARS-CoV-2/pathogenicity , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adult , Aged , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , Blood Platelets/drug effects , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Coronary Artery Disease/complications , Coronary Artery Disease/drug therapy , Coronary Artery Disease/mortality , Coronary Artery Disease/virology , Diabetes Mellitus/drug therapy , Diabetes Mellitus/mortality , Diabetes Mellitus/virology , Disseminated Intravascular Coagulation/complications , Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/virology , Drug Combinations , Female , Hospital Mortality , Humans , Hypertension/complications , Hypertension/drug therapy , Hypertension/mortality , Hypertension/virology , Iran , Lopinavir/therapeutic use , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Male , Middle Aged , Pulmonary Embolism/complications , Pulmonary Embolism/mortality , Pulmonary Embolism/virology , Respiration, Artificial/mortality , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2/drug effects , Severity of Illness Index , Survival Analysis , Treatment Outcome
5.
J Med Virol ; 93(9): 5390-5395, 2021 09.
Article in English | MEDLINE | ID: covidwho-1206845

ABSTRACT

Hypercoagulability and thrombosis caused by coronavirus disease 2019 (COVID-19) are related to the higher mortality rate. Because of limited data on the antiplatelet effect, we aimed to evaluate the impact of aspirin add-on therapy on the outcome of the patients hospitalized due to severe COVID-19. In this cohort study, patients with a confirmed diagnosis of severe COVID-19 admitted to Imam Hossein Medical Center, Tehran, Iran from March 2019 to July 2020 were included. Demographics and related clinical data during their hospitalization were recorded. The mortality rate of the patients was considered as the primary outcome and its association with aspirin use was assessed. Nine hundred and ninety-one patients were included, of that 336 patients (34%) received aspirin during their hospitalization and 655 ones (66%) did not. Comorbidities were more prevalent in the patients who were receiving aspirin. Results from the multivariate COX proportional model demonstrated a significant independent association between aspirin use and reduction in the risk of in-hospital mortality (0.746 [0.560-0.994], p = 0.046). Aspirin use in hospitalized patients with COVID-19 is associated with a significant decrease in mortality rate. Further prospective randomized controlled trials are needed to assess the efficacy and adverse effects of aspirin administration in this population.


Subject(s)
Aspirin/therapeutic use , COVID-19/drug therapy , Disseminated Intravascular Coagulation/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Pulmonary Embolism/drug therapy , SARS-CoV-2/pathogenicity , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Adult , Aged , Alanine/analogs & derivatives , Alanine/therapeutic use , Antiviral Agents/therapeutic use , Blood Platelets/drug effects , Blood Platelets/pathology , Blood Platelets/virology , COVID-19/complications , COVID-19/mortality , COVID-19/virology , Coronary Artery Disease/complications , Coronary Artery Disease/drug therapy , Coronary Artery Disease/mortality , Coronary Artery Disease/virology , Diabetes Mellitus/drug therapy , Diabetes Mellitus/mortality , Diabetes Mellitus/virology , Disseminated Intravascular Coagulation/complications , Disseminated Intravascular Coagulation/mortality , Disseminated Intravascular Coagulation/virology , Drug Combinations , Female , Hospital Mortality , Humans , Hypertension/complications , Hypertension/drug therapy , Hypertension/mortality , Hypertension/virology , Iran , Lopinavir/therapeutic use , Lung/blood supply , Lung/drug effects , Lung/pathology , Lung/virology , Male , Middle Aged , Pulmonary Embolism/complications , Pulmonary Embolism/mortality , Pulmonary Embolism/virology , Respiration, Artificial/mortality , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Ritonavir/therapeutic use , SARS-CoV-2/drug effects , Severity of Illness Index , Survival Analysis , Treatment Outcome
6.
J Cell Mol Med ; 25(2): 1263-1273, 2021 01.
Article in English | MEDLINE | ID: covidwho-1060602

ABSTRACT

To determine whether pre-hospitalization use of aspirin is associated with all-cause mortality in coronavirus disease 2019 (COVID-19) patients with coronary artery disease (CAD). We recruited 183 adult patients with CAD diagnosed with COVID-19, including 52 taking low-dose aspirin (mean [SD] age, 69.7 [1.1] years; 59.6% men) and 131 without using aspirin (mean [SD] age, 71.8 [0.9] years; 51.9% men), who were admitted in the Tongji hospital in Wuhan, China from January 10, 2020 to March 30, 2020. There was no difference on in-hospital mortality between aspirin group and non-aspirin group (21.2% vs. 22.1%, P = .885). Similarly, for critically severe COVID-19 patients, the mortality in aspirin group was close to that in non-aspirin group (44% vs. 45.9%, P = .872). Moreover, the percentage of patients with CAD taking low-dose aspirin did not differ between those survivors and non-survivors (28.7% vs. 27.5%, P = .885). Meanwhile, the usage of aspirin was not correlated with all-cause mortality in multivariate analysis (OR = 0.944, 95% CI: 0.411-2.172, P = .893). Collectively, our study suggested that the pre-hospitalization use of low-dose aspirin was not associated with the clinical outcome of patients with CAD hospitalized with COVID-19 infections.


Subject(s)
Aspirin/administration & dosage , COVID-19/mortality , Coronary Artery Disease/drug therapy , Coronary Artery Disease/mortality , Aged , China , Coronary Artery Disease/virology , Female , Hospital Mortality , Hospitalization , Humans , Male , Retrospective Studies
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