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Cardiovascular Therapeutics 2020Antiplatelet therapy is the mainstay of treatment and secondary prevention of cardiovascular disease (CVD), including acute coronary syndrome (ACS), transient ischemic... (Review)
Review
Antiplatelet therapy is the mainstay of treatment and secondary prevention of cardiovascular disease (CVD), including acute coronary syndrome (ACS), transient ischemic attack (TIA) or minor stroke, and peripheral artery disease (PAD). The P2Y inhibitors, of which clopidogrel was the first, play an integral role in antiplatelet therapy and therefore in the treatment and secondary prevention of CVD. This review discusses the available evidence concerning antiplatelet therapy in patients with CVD, with a focus on the role of clopidogrel. In combination with aspirin, clopidogrel is often used as part of dual antiplatelet therapy (DAPT) for the secondary prevention of ACS. Although newer, more potent P2Y inhibitors (prasugrel and ticagrelor) show a greater reduction in ischemic risk compared with clopidogrel in randomized trials of ACS patients, these newer P2Y inhibitors are often associated with an increased risk of bleeding. Deescalation of DAPT by switching from prasugrel or ticagrelor to clopidogrel may be required in some patients with ACS. Furthermore, real-world studies of ACS patients have not confirmed the benefits of the newer P2Y inhibitors over clopidogrel. In patients with very high-risk TIA or stroke, short-term DAPT with clopidogrel plus aspirin for 21-28 days, followed by clopidogrel monotherapy for up to 90 days, is recommended. Clopidogrel monotherapy may also be used in patients with symptomatic PAD. In conclusion, there is strong evidence supporting the use of clopidogrel antiplatelet therapy in several clinical settings, which emphasizes the importance of this medication in clinical practice.
Topics: Blood Platelets; Cardiovascular Diseases; Clopidogrel; Hemorrhage; Humans; Platelet Activation; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Secondary Prevention; Treatment Outcome
PubMed: 32284734
DOI: 10.1155/2020/8703627 -
Romanian Journal of Internal Medicine =... Dec 2019Immune thrombocytopenia is an autoimmune hematological disorder characterized by severely decreased platelet count of peripheral cause: platelet destruction via... (Review)
Review
Immune thrombocytopenia is an autoimmune hematological disorder characterized by severely decreased platelet count of peripheral cause: platelet destruction via antiplatelet antibodies which may also affect marrow megakaryocytes. Patients may present in critical situations, with cutaneous and/or mucous bleeding and possibly life-threatening organ hemorrhages (cerebral, digestive, etc.) Therefore, rapid diagnosis and therapeutic intervention are mandatory. Corticotherapy represents the first treatment option, but as in any autoimmune disorder, there is a high risk of relapse. Second line therapy options include: intravenous immunoglobulins, thrombopoietin receptor agonists, rituximab or immunosuppression, but their benefit is usually temporary. Moreover, the disease generally affects young people who need repeated and prolonged treatment and hospitalization and therefore, it is preferred to choose a long term effect therapy. Splenectomy - removal of the site of platelet destruction - represents an effective and stable treatment, with 70-80% response rate and low complications incidence. A challenging situation is the association of ITP with pregnancy, which further increases the risk due to the immunodeficiency of pregnancy, major dangers of bleeding, vital risks for mother and fetus, potential risks of medication, necessity of prompt intervention in the setting of specific obstetrical situations - delivery, pregnancy loss, obstetrical complications, etc. We present an updated review of the current clinical and laboratory data, as well as a detailed analysis of the available therapeutic options with their benefits and risks, and also particular associations (pregnancy, relapsed and refractory disease, emergency treatment).
Topics: Diagnosis, Differential; Emergency Treatment; Female; Humans; Pregnancy; Pregnancy Complications; Purpura, Thrombocytopenic, Idiopathic
PubMed: 31199777
DOI: 10.2478/rjim-2019-0014 -
The Cochrane Database of Systematic... Feb 2023Diabetic retinopathy (DR) is characterised by neurovascular degeneration as a result of chronic hyperglycaemia. Proliferative diabetic retinopathy (PDR) is the most... (Review)
Review
BACKGROUND
Diabetic retinopathy (DR) is characterised by neurovascular degeneration as a result of chronic hyperglycaemia. Proliferative diabetic retinopathy (PDR) is the most serious complication of DR and can lead to total (central and peripheral) visual loss. PDR is characterised by the presence of abnormal new blood vessels, so-called "new vessels," at the optic disc (NVD) or elsewhere in the retina (NVE). PDR can progress to high-risk characteristics (HRC) PDR (HRC-PDR), which is defined by the presence of NVD more than one-fourth to one-third disc area in size plus vitreous haemorrhage or pre-retinal haemorrhage, or vitreous haemorrhage or pre-retinal haemorrhage obscuring more than one disc area. In severe cases, fibrovascular membranes grow over the retinal surface and tractional retinal detachment with sight loss can occur, despite treatment. Although most, if not all, individuals with diabetes will develop DR if they live long enough, only some progress to the sight-threatening PDR stage. OBJECTIVES: To determine risk factors for the development of PDR and HRC-PDR in people with diabetes and DR.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; which contains the Cochrane Eyes and Vision Trials Register; 2022, Issue 5), Ovid MEDLINE, and Ovid Embase. The date of the search was 27 May 2022. Additionally, the search was supplemented by screening reference lists of eligible articles. There were no restrictions to language or year of publication. SELECTION CRITERIA: We included prospective or retrospective cohort studies and case-control longitudinal studies evaluating prognostic factors for the development and progression of PDR, in people who have not had previous treatment for DR. The target population consisted of adults (≥18 years of age) of any gender, sexual orientation, ethnicity, socioeconomic status, and geographical location, with non-proliferative diabetic retinopathy (NPDR) or PDR with less than HRC-PDR, diagnosed as per standard clinical practice. Two review authors independently screened titles and abstracts, and full-text articles, to determine eligibility; discrepancies were resolved through discussion. We considered prognostic factors measured at baseline and any other time points during the study and in any clinical setting. Outcomes were evaluated at three and eight years (± two years) or lifelong. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data from included studies using a data extraction form that we developed and piloted prior to the data collection stage. We resolved any discrepancies through discussion. We used the Quality in Prognosis Studies (QUIPS) tool to assess risk of bias. We conducted meta-analyses in clinically relevant groups using a random-effects approach. We reported hazard ratios (HR), odds ratios (OR), and risk ratios (RR) separately for each available prognostic factor and outcome, stratified by different time points. Where possible, we meta-analysed adjusted prognostic factors. We evaluated the certainty of the evidence with an adapted version of the GRADE framework. MAIN RESULTS: We screened 6391 records. From these, we identified 59 studies (87 articles) as eligible for inclusion. Thirty-five were prospective cohort studies, 22 were retrospective studies, 18 of which were cohort and six were based on data from electronic registers, and two were retrospective case-control studies. Twenty-three studies evaluated participants with type 1 diabetes (T1D), 19 with type 2 diabetes (T2D), and 17 included mixed populations (T1D and T2D). Studies on T1D included between 39 and 3250 participants at baseline, followed up for one to 45 years. Studies on T2D included between 100 and 71,817 participants at baseline, followed up for one to 20 years. The studies on mixed populations of T1D and T2D ranged from 76 to 32,553 participants at baseline, followed up for four to 25 years. We found evidence indicating that higher glycated haemoglobin (haemoglobin A1c (HbA1c)) levels (adjusted OR ranged from 1.11 (95% confidence interval (CI) 0.93 to 1.32) to 2.10 (95% CI 1.64 to 2.69) and more advanced stages of retinopathy (adjusted OR ranged from 1.38 (95% CI 1.29 to 1.48) to 12.40 (95% CI 5.31 to 28.98) are independent risk factors for the development of PDR in people with T1D and T2D. We rated the evidence for these factors as of moderate certainty because of moderate to high risk of bias in the studies. There was also some evidence suggesting several markers for renal disease (for example, nephropathy (adjusted OR ranged from 1.58 (95% CI not reported) to 2.68 (2.09 to 3.42), and creatinine (adjusted meta-analysis HR 1.61 (95% CI 0.77 to 3.36)), and, in people with T1D, age at diagnosis of diabetes (< 12 years of age) (standardised regression estimate 1.62, 95% CI 1.06 to 2.48), increased triglyceride levels (adjusted RR 1.55, 95% CI 1.06 to 1.95), and larger retinal venular diameters (RR 4.28, 95% CI 1.50 to 12.19) may increase the risk of progression to PDR. The certainty of evidence for these factors, however, was low to very low, due to risk of bias in the included studies, inconsistency (lack of studies preventing the grading of consistency or variable outcomes), and imprecision (wide CIs). There was no substantial and consistent evidence to support duration of diabetes, systolic or diastolic blood pressure, total cholesterol, low- (LDL) and high- (HDL) density lipoproteins, gender, ethnicity, body mass index (BMI), socioeconomic status, or tobacco and alcohol consumption as being associated with incidence of PDR. There was insufficient evidence to evaluate prognostic factors associated with progression of PDR to HRC-PDR. AUTHORS' CONCLUSIONS: Increased HbA1c is likely to be associated with progression to PDR; therefore, maintaining adequate glucose control throughout life, irrespective of stage of DR severity, may help to prevent progression to PDR and risk of its sight-threatening complications. Renal impairment in people with T1D or T2D, as well as younger age at diagnosis of diabetes mellitus (DM), increased triglyceride levels, and increased retinal venular diameters in people with T1D may also be associated with increased risk of progression to PDR. Given that more advanced DR severity is associated with higher risk of progression to PDR, the earlier the disease is identified, and the above systemic risk factors are controlled, the greater the chance of reducing the risk of PDR and saving sight.
Topics: Adult; Female; Humans; Male; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Glycated Hemoglobin; Prognosis; Prospective Studies; Retinal Hemorrhage; Retrospective Studies; Triglycerides; Vitreous Hemorrhage
PubMed: 36815723
DOI: 10.1002/14651858.CD013775.pub2 -
Revista Espanola de Enfermedades... Nov 2023A 76-year-old man with multiple cardiovascular risk factors (hypertension, DM2, LD, smoker) and severe peripheral arterial disease (iliofemoral bypass, supracondylar...
A 76-year-old man with multiple cardiovascular risk factors (hypertension, DM2, LD, smoker) and severe peripheral arterial disease (iliofemoral bypass, supracondylar amputation) came to the emergency with coffee ground emesis and mild anemia. Urgent gastroscopy showed diffuse circumferential black mucosa covered by fibrin affecting the middle and distal esophageal third. Acute esophageal necrosis is a rare cause of gastrointestinal bleeding that should be suspected in patients with cardiovascular risk factors with an image of a black esophagus that is abruptly interrupted at the EGJ.
Topics: Male; Humans; Aged; Necrosis; Esophageal Diseases; Hematemesis; Gastrointestinal Hemorrhage; Acute Disease
PubMed: 36205331
DOI: 10.17235/reed.2022.9217/2022 -
Journal of Translational Medicine Mar 2023Owing to metabolic disequilibrium and immune suppression, intracerebral hemorrhage (ICH) patients are prone to infections; according to a recent global analysis of...
BACKGROUND
Owing to metabolic disequilibrium and immune suppression, intracerebral hemorrhage (ICH) patients are prone to infections; according to a recent global analysis of stroke cases, approximately 10 million new-onset ICH patients had experienced concurrent infection. However, the intrinsic mechanisms underlying the effects of infection related peripheral inflammation after ICH remain unclear.
METHODS
Lipopolysaccharide (LPS) was intraperitoneally injected into ICH model mice to induce peripheral inflammation. Neurobehavioral deficits, blood‒brain barrier (BBB) disruption, and the expression of CCR5, JAK2, STAT3, and MMP9 were evaluated after treatment with recombinant CCL5 (rCCL5) (a CCR5 ligand), maraviroc (MVC) (an FDA-approved selective CCR5 antagonist), or JAK2 CRISPR plasmids.
RESULTS
Our study revealed that severe peripheral inflammation increased CCL5/CCR5 axis activation in multiple inflammatory cell types, including microglia, astrocytes, and monocytes, and aggravated BBB disruption and neurobehavioral dysfunction after ICH, possibly in part through the JAK2/STAT3 signaling pathway.
CONCLUSIONS
CCR5 might be a potential target for the clinical treatment of infection-induced exacerbation of BBB disruption following ICH.
Topics: Animals; Mice; Astrocytes; Blood-Brain Barrier; Cerebral Hemorrhage; Inflammation; Stroke
PubMed: 36918921
DOI: 10.1186/s12967-023-04044-3 -
Journal of Biomedical Science Aug 2022Increasing evidences have suggested an important role of microRNAs (miRNAs) in regulating cell death processes including NETosis and apoptosis. Dysregulated expression...
BACKGROUND
Increasing evidences have suggested an important role of microRNAs (miRNAs) in regulating cell death processes including NETosis and apoptosis. Dysregulated expression of miRNAs and increased formation of neutrophil extracellular traps (NETs) and apoptosis participate in autoimmune-mediated diffuse alveolar hemorrhage (DAH), mostly associated with pulmonary capillaritis in systemic lupus erythematosus (SLE) patients. In particular, besides the inhibition of apoptosis, miR-146a can control innate and acquired immune responses, and regulate the toll-like receptor pathway through targeting TRAF6 to reduce the expression of pro-inflammatory cytokines/chemokines like IL-8, a NETosis inducer.
METHODS
Expression of miR-146a, TRAF6 and NETs were examined in peripheral blood neutrophils (PBNs) and lung tissues from SLE-associated DAH patients, and in neutrophils and pristane-induced DAH lung tissues from C57BL/6 mice. To assess NETs formation, we examined NETosis-related DNAs morphology and crucial mediators including protein arginine deiminase 4 and citrullinated Histone 3. Expression of miR-146a and its endogenous RNA SNHG16 were studied in HL-60 promyelocytic cells and MLE-12 alveolar cells during NETosis and apoptosis processes, respectively. MiR-146a-overexpressed and CRISPR-Cas13d-mediated SNHG16-silenced HL-60 cells were investigated for NETosis. MiR-146a-overexpressed MLE-12 cells were analyzed for apoptosis. Pristane-injected mice received intra-pulmonary miR-146a delivery to evaluate therapeutic efficacy in DAH.
RESULTS
In DAH patients, there were down-regulated miR-146a levels with increased TRAF6 expression and PMA/LPS-induced NETosis in PBNs, and down-regulated miR-146a levels with increased TRAF6, high-mobility group box 1 (HMGB1), IL-8, NETs and apoptosis expression in lung tissues. HMGB1-stimulated mouse neutrophils had down-regulated miR-146a levels with increased TRAF6, IL-8 and NETs expression. PMA-stimulated HL-60 cells had down-regulated miR-146a levels with enhanced NETosis. MiR-146a-overexpressed or SNHG16-silenced HL-60 cells showed reduced NETosis. Apoptotic MLE-12 cells had down-regulated miR-146a expression and increased HMGB1 release, while miR-146a-overexpressed MLE-12 cells showed reduced apoptosis and HMGB1 production. There were down-regulated miR-146a levels with increased TRAF6, HMGB1, IL-8, NETs and apoptosis expression in mouse DAH lung tissues. Intra-pulmonary miR-146a delivery could suppress DAH by reducing TRAF6, IL-8, NETs and apoptosis expression.
CONCLUSIONS
Our results demonstrate firstly down-regulated pulmonary miR-146a levels with increased TRAF6 and IL-8 expression and NETs and apoptosis formation in autoimmune-mediated DAH, and implicate a therapeutic potential of intra-pulmonary miR-146a delivery.
Topics: Animals; Apoptosis; Extracellular Traps; HMGB1 Protein; Hemorrhage; Humans; Interleukin-8; Lung Diseases; Lupus Erythematosus, Systemic; Mice; Mice, Inbred C57BL; MicroRNAs; Neutrophils; TNF Receptor-Associated Factor 6
PubMed: 36028828
DOI: 10.1186/s12929-022-00849-4 -
Acta Bio-medica : Atenei Parmensis Jul 2020Good knowledge of the various approaches of embolization of peripheral bleedings and different embolic materials available is of paramount importance for successful and... (Review)
Review
Good knowledge of the various approaches of embolization of peripheral bleedings and different embolic materials available is of paramount importance for successful and safe embolization. We review and illustrate the main endovascular and percutaneous techniques used for embolization, along with the characteristics of the different embolic materials, and the potential complications.
Topics: Embolism; Embolization, Therapeutic; Hemorrhage; Humans; Treatment Outcome
PubMed: 32945281
DOI: 10.23750/abm.v91i8-S.9974 -
Journal of Cerebral Blood Flow and... Feb 2023Stroke is a sudden and rapidly progressing ischemic or hemorrhagic cerebrovascular disease. When stroke damages the brain, the immune system becomes hyperactive, leading... (Review)
Review
Stroke is a sudden and rapidly progressing ischemic or hemorrhagic cerebrovascular disease. When stroke damages the brain, the immune system becomes hyperactive, leading to systemic inflammatory response and immunomodulatory disorders, which could significantly impact brain damage, recovery, and prognosis of stroke. Emerging researches suggest that ischemic stroke-induced spleen contraction could activate a peripheral immune response, which may further aggravate brain injury. This review focuses on hemorrhagic strokes including intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) and discusses the central nervous system-peripheral immune interactions after hemorrhagic stroke induction. First, inflammatory progression after ICH and SAH is investigated. As a part of this review, we summarize the various kinds of inflammatory cell infiltration to aggravate brain injury after blood-brain barrier interruption induced by hemorrhagic stroke. Then, we explore hemorrhagic stroke-induced systemic inflammatory response syndrome (SIRS) and discuss the interactions of CNS and peripheral inflammatory response. In addition, potential targets related to inflammatory response for ICH and SAH are discussed in this review, which may lead to novel therapeutic strategies for hemorrhagic stroke.
Topics: Humans; Hemorrhagic Stroke; Cerebral Hemorrhage; Stroke; Subarachnoid Hemorrhage; Blood-Brain Barrier; Brain Injuries
PubMed: 36476130
DOI: 10.1177/0271678X221145089 -
PloS One 2022The objectives of this study were to evaluate the proper anticoagulants coated in blood-collecting tube for the peripheral blood mononuclear cells (PBMCs) isolation and...
The objectives of this study were to evaluate the proper anticoagulants coated in blood-collecting tube for the peripheral blood mononuclear cells (PBMCs) isolation and to evaluate the proper culture temperature for the Varanus salvator's PBMCs, in addition, the hematological characteristics also reported. The heparin treated blood (n = 10) and EDTA treated blood (n = 10) from Varanus salvator were obtained for PBMCs evaluation. The PBMCs obtained from the heparin treated blood was significantly higher than that of EDTA treated blood during the culture period (P < 0.05) indicated heparin would be more appropriated anticoagulant for blood collection. The PBMCs cultured under 37°C and 27°C were not significantly difference on first three days but 37°C showed significantly higher effect in the following days (P < 0.05) indicated both temperatures can be used which 37°C should be an optimal for PBMCs preparation. The peripheral blood cells of Varanus salvator (n = 49) were analyzed for hematological profiles and characteristics which the number of erythrocytes 1.19 ± 0.04 x 1012/L (1.17-1.35 x 1012/L) and WBC 2.41 ± 0.13 x 109/L (2.29-2.81 x 109/L) with absolute differential count of heterophils 0.92 ± 0.02 x 109/L (0.87-0.95 x 109/L), lymphocytes 1.17 ± 0.01 x 109/L (1.15-1.23 x 109/L), azurophils 0.40 ± 0.01 x 109/L (0.37-0.42 x 109/L), basophils 0.000 ± 0.001 x 109/L (0.004-0.011 x 109/L) and monocytes 0.027 ± 0.002 x 109/L (0.028-0.039 x 109/L). These results would play an important role on the cell immunological studies of the Varanus salvator in the future.
Topics: Animals; Anticoagulants; Edetic Acid; Hematology; Heparin; Leukocyte Count; Leukocytes, Mononuclear; Lizards
PubMed: 35867719
DOI: 10.1371/journal.pone.0269108 -
Clinical and Translational Medicine Jul 2023The first-line therapy is effective for the treatment of primary immune thrombocytopenia (ITP); however, maintaining the long-term responses remains challenging....
BACKGROUND
The first-line therapy is effective for the treatment of primary immune thrombocytopenia (ITP); however, maintaining the long-term responses remains challenging. Low-dose decitabine (DAC) has been adopted to treat refractory ITP, while its role in macrophage polarization has not been fully understood. We aimed to investigate the mechanistic role of DAC in M2 macrophage polarization and evaluated its therapeutic effect in ITP.
METHODS
The M2 monocytes were identified by flow cytometry from peripheral blood mononuclear cells in healthy controls (HCs) and ITP patients. The expression of PPARγ, Arg-1, DNMT3b and NLRP3, together with IL-10 plasma levels was measured to examine its function. Bisulfite-sequencing PCR was used to evaluate the methylation status of PPARγ promoter, and the binding affinity of KLF4 was measured by Cut&Tag. A sh-PPARγ THP-1 cell line was created to verify if low-dose DAC-modulated M2 macrophage polarization was PPARγ-dependent. The passive ITP models were used to investigate the therapeutic effects of low-dose DAC and its role in modulating polarization and immunomodulatory function of macrophages. NLRP3 inflammasome and reactive oxygen species were also tested to understand the downstream of PPARγ.
RESULTS
The M2 monocytes with impaired immunoregulation were observed in ITP. After high-dose dexamethasone (HD-DXM) treatment, M2 monocytes increased significantly with the elevated expression of PPARγ, Arg-1 and IL-10 in CR patients. Low-dose DAC promoted M2 macrophage polarization in a PPARγ-dependent way via demethylating the promoter of PPARγ, especially the KLF4 binding sites. Low-dose DAC alleviated ITP mice by restoring the M1/M2 balance and fine-tuning immunomodulatory function of macrophages. The downstream of the PPARγ modulation of M2 macrophage polarization might physiologically antagonize NLRP3 inflammasome.
CONCLUSIONS
Low-dose DAC promoted M2 macrophage polarization due to the demethylation within the promoter of PPARγ, thus enhanced the KLF4 binding affinity in ITP.
Topics: Animals; Mice; PPAR gamma; Decitabine; Interleukin-10; Inflammasomes; Leukocytes, Mononuclear; NLR Family, Pyrin Domain-Containing 3 Protein; Purpura, Thrombocytopenic, Idiopathic; Macrophages
PubMed: 37488670
DOI: 10.1002/ctm2.1344