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Objective: We tested the hypothesis that targeted TMLR combined with intramyocardial injection of autologous CD 133+ progenitor cells is safe and feasible in patients with chronic ischemic cardiomyopathy (ICM) and no revascularization options. Methods: Eight male patients (age 62 ± 2.4 years) with multivessel severe ischemic heart disease and no revascularization options were enrolled. Autologous CD 133 + endothelial progenitor cells were derived and purified from the bone marrow on the day of surgery using the clinical-grade closed CliniMACS system. Using a lateral thoracotomy approach, TMLR was performed, followed by transmyocardial transplantation of purified CD133 + cells (mean number of transplanted cells: 12.5 × 106) in the region surrounding the TMLR sites. These sites were selected based on ischemia on pre-procedure perfusion imaging. We performed clinical and myocardial perfusion imaging pre-procedure and then at 6- and 12-month follow-up. Results: No major complications or death occurred during the procedure or during the peri-operative hospital stay. One patient died of cardiac cause 6 months post-procedure. There was a reported short-term improvement in anginal and heart failure symptoms and a modest reduction in the ischemic score as assessed by perfusion imaging. Conclusions: Our phase 1 clinical study examining the combination therapy of targeted transmyocardial laser revascularization therapy and autologous CD133 + endothelial progenitor cells in patients with chronic ICM and no revascularization options demonstrates the feasibility and short-term safety of this combined approach and warrants future larger phase 2 randomized clinical studies. [ABSTRACT FROM AUTHOR]

Potassium bromate (KBrO3) is classified by the International Agency for Research on Cancer as a carcinogenic compound, where it causes renal tumors. The present study investigated the potential curative effect of metformin loaded on gold nanoparticles (MET AuNPs) in attenuating KBrO3-induced nephrotoxicity. Rats were divided into eight groups (control, MET, AuNPs, MET AuNPs, KBrO3, KBrO3/MET, KBrO3/AuNPS, and KBrO3/MET AuNPs). KBrO3 administration resulted in a significant elevation in serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total protein (TP), albumin (Alb), total bilirubin (TB), direct bilirubin (DB), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), creatinine, urea, uric acid. Also, KBrO3 significantly increased renal malondialdehyde (MDA), protein carbonyl (PC), and nitric oxide (NO) levels and reduced the activities of antioxidant molecules superoxide dismutase (SOD), catalase (CAT), glutathione-S-transferase (GST), and Reduced glutathione (GSH). It also caused damaged DNA spots in comet assay and increased inflammatory IL-6 and apoptotic markers (caspase 3, Bax) while antiapoptotic Bcl-2 was significantly reduced. MET, AuNPS, MET AuNPS reduced the extent of renal damage induced by KBrO3 as indicated by decreased (AST, ALT, ALP, Alb, TP, TB, DB, creatinine, urea, uric, Lipid profile). MET, AuNPS, MET AuNPS showed a good curative effect against KBrO3-induced nephrotoxicity and MET AuNPS group showed better results compared with monotherapy. [ABSTRACT FROM AUTHOR]

Fast and efficient homing and engraftment of hematopoietic stem progenitor cells (HSPCs) is crucial for positive clinical outcomes from transplantation. We found that this process depends on activation of the Nlrp3 inflammasome, both in the HSPCs to be transplanted and in the cells in the recipient bone marrow (BM) microenvironment. For the first time we provide evidence that functional deficiency in the Nlrp3 inflammasome in transplanted cells or in the host microenvironment leads to defective homing and engraftment. At the molecular level, functional deficiency of the Nlrp3 inflammasome in HSPCs leads to their defective migration in response to the major BM homing chemoattractant stromal-derived factor 1 (SDF-1) and to other supportive chemoattractants, including sphingosine-1-phosphate (S1P) and extracellular adenosine triphosphate (eATP). We report that activation of the Nlrp3 inflammasome increases autocrine release of eATP, which promotes incorporation of the CXCR4 receptor into membrane lipid rafts at the leading surface of migrating cells. On the other hand, a lack of Nlrp3 inflammasome expression in BM conditioned for transplantation leads to a decrease in expression of SDF-1 and danger-associated molecular pattern molecules (DAMPs), which are responsible for activation of the complement cascade (ComC), which in turn facilitates the homing and engraftment of HSPCs. [ABSTRACT FROM AUTHOR]

Background: Myocardial infarction (MI) triggers myelopoiesis, resulting in heightened production of neutrophils. However, the mechanisms that sustain their production and recruitment to the injured heart are unclear.Methods: Using a mouse model of the permanent ligation of the left anterior descending artery and flow cytometry, we first characterized the temporal and spatial effects of MI on different myeloid cell types. We next performed global transcriptome analysis of different cardiac cell types within the infarct to identify the drivers of the acute inflammatory response and the underlying signaling pathways. Using a combination of genetic and pharmacological strategies, we identified the sequelae of events that led to MI-induced myelopoiesis. Cardiac function was assessed by echocardiography. The association of early indexes of neutrophilia with major adverse cardiovascular events was studied in a cohort of patients with acute MI.Results: Induction of MI results in rapid recruitment of neutrophils to the infarct, where they release specific alarmins, S100A8 and S100A9. These alarmins bind to the Toll-like receptor 4 and prime the nod-like receptor family pyrin domain-containing 3 inflammasome in naïve neutrophils and promote interleukin-1β secretion. The released interleukin-1β interacts with its receptor (interleukin 1 receptor type 1) on hematopoietic stem and progenitor cells in the bone marrow and stimulates granulopoiesis in a cell-autonomous manner. Genetic or pharmacological strategies aimed at disruption of S100A8/A9 and their downstream signaling cascade suppress MI-induced granulopoiesis and improve cardiac function. Furthermore, in patients with acute coronary syndrome, higher neutrophil count on admission and after revascularization correlates positively with major adverse cardiovascular disease outcomes.Conclusions: Our study provides novel evidence for the primary role of neutrophil-derived alarmins (S100A8/A9) in dictating the nature of the ensuing inflammatory response after myocardial injury. Therapeutic strategies aimed at disruption of S100A8/A9 signaling or their downstream mediators (eg, nod-like receptor family pyrin domain-containing 3 inflammasome, interleukin-1β) in neutrophils suppress granulopoiesis and may improve cardiac function in patients with acute coronary syndrome. [ABSTRACT FROM AUTHOR]

Purpose. Investigating the efficacy of intravitreal injection of erythropoietin (EPO) in managing indirect traumatic optic neuropathy (ITON) of different durations. Methods. A case series that included two groups of ITON patients: recent ITON group (<3 months trauma duration; 7 eyes) and old duration ITON group (3–36 months; 7 eyes). Diagnostic computerized tomography (CT) and baseline flash visual evoked response (VER) were performed at the presentation time. At the initial visit and each follow-up, all patients had undergone assessment of best-corrected visual acuity (BCVA), pupil reaction, and anterior and posterior segments. VER was repeated 1 and 3 months after injection. All patients received an intravitreal injection of 2000 IU EPO in 0.2 ml of commercially available sterile EPREX 4000 solution, Jansen Cilag, Zug, Switzerland. Five patients had received a second injection 3 months later. Results. Significant improvement was found in BCVA, VER amplitude, and latency (P<0.0001, 0.0154, and 0.0291, respectively). Initial values of BCVA, VER amplitude, and latency correlated significantly to the final values. Differences between recent and old trauma groups were insignificant in the three parameters. In patients who received second injection, further clinical but statistically insignificant improvement was noted in BCVA in 60% of patients, VER amplitude in 50% of patients, and in VER latency in 100% of patients. No complications were recorded. Conclusion. Intravitreal injection of EPO may be effective and safe in treatment of recent and old indirect traumatic optic neuropathy. [ABSTRACT FROM AUTHOR]

The article focuses on the negative impact of noncompliance (NC) and leaving against medical advice (LAMA) on the hospital mortality and health of the patients. It talks about the clinical management involved in NC patients with acute myocardial infarction (AMI). It tells about NC being higher in Hispanic and black young male patients with AMI who belong to the lower income group.

The role of intellectual property rights (IPRs) in the development and transfer of climate change technologies has been a contentious issue in negotiations under the United Nations Framework Convention on Climate Change (UNFCCC). Irreconcilable differences seem to oppose those who believe IPRs are an inherent barrier to the transfer of climate change technologies and those who argue they are an essential incentive to innovation. After providing an overview of the polarized debate on this issue, this article reviews the existing literature and empirical evidence and looks into some practical initiatives and recent developments. Finally, it seeks to identify a way forward that could help overcome the current stalemate in international deliberations by suggesting a number of parameters to structure the discussion on this complex issue. [ABSTRACT FROM AUTHOR]

Hematopoietic cytokines, traditionally known to influence cellular proliferation, differentiation, maturation, and lineage commitment in the bone marrow, include granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, stem cell factor, Flt-3 ligand, and erythropoietin among others. Emerging evidence suggests that these cytokines also exert multifarious biological effects on diverse nonhematopoietic organs and tissues. Although the precise mechanisms remain unclear, numerous studies in animal models of myocardial infarction (MI) and heart failure indicate that hematopoietic cytokines confer potent cardiovascular benefits, possibly through mobilization and subsequent homing of bone marrow-derived cells into the infarcted heart with consequent induction of myocardial repair involving multifarious mechanisms. In addition, these cytokines are also known to exert direct cytoprotective effects. However, results from small-scale clinical trials of G-CSF therapy as a single agent after acute MI have been discordant and largely disappointing. It is likely that cardiac repair following cytokine therapy depends on a number of known and unknown variables, and further experimental and clinical studies are certainly warranted to accurately determine the true therapeutic potential of such therapy. In this review, we discuss the biological features of several key hematopoietic cytokines and present the basic and clinical evidence pertaining to cardiac repair with hematopoietic cytokine therapy. [ABSTRACT FROM AUTHOR]

(J Interven Cardiol 2010;23:565-568) [ABSTRACT FROM AUTHOR]

Chest Trauma in athletes is a common health problem. However, myocardial infarction secondary to coronary dissection in the setting of blunt chest trauma is extremely rare. We report a case of acute inferior wall myocardial infarction following blunt chest trauma. A 32-year-old male with no relevant medical problems was transferred to our medical center for retrosternal chest pain after being elbowed in the chest during a soccer game. Few seconds later, he started experiencing sharp retrosternal chest pain that was severe to that point where he called the emergency medical service. Upon arrival to the trauma department patient was still complaining of chest pain. ECG demonstrated ST segment elevation in the inferior leads with reciprocal changes in the lateral leads all consistent with active ischemia. After rolling out aortic dissection, patient was loaded with ASA, ticagerlor, heparin and was emergently taken to the cardiac catheterization lab. Coronary angiography demonstrated 100% thrombotic occlusion in the distal right coronary artery with TIMI 0 flow distally. After thrombus aspiration, a focal dissection was noted on the angiogram that was successfully stented. Two days after admission patient was discharged home. Echocardiography prior to discharge showed inferior wall akinesis, normal right ventricular systolic function and normal overall ejection fraction. [ABSTRACT FROM AUTHOR]

The optimal medium for cardiac differentiation of adult primitive cells remains to be established. We quantitatively compared the efficacy of IGF-1, dynorphin B, insulin, oxytocin, bFGF, and TGF-β1 in inducing cardiomyogenic differentiation. Adult mouse skeletal muscle-derived Sca1+/CD45-/c-kit-/Thy-1+ (SM+) and Sca1-/CD45-/c-kit-/Thy-1+ (SM-) cells were cultured in basic medium (BM; DMEM, FBS, IGF-1, dynorphin B) alone and BM supplemented with insulin, oxytocin, bFGF, or TGF-β1. Cardiac differentiation was evaluated by the expression of cardiac-specific markers at the mRNA (qRT-PCR) and protein (immunocytochemistry) levels. BM+TGF-β1 upregulated mRNA expression of Nkx2.5 and GATA-4 after 4 days and Myl2 after 9 days. After 30 days, BM+TGF-β1 induced the greatest extent of cardiac differentiation (by morphology and expression of cardiac markers) in SM- cells. We conclude that TGF-β1 enhances cardiomyogenic differentiation in skeletal muscle-derived adult primitive cells. This strategy may be utilized to induce cardiac differentiation as well as to examine the cardiomyogenic potential of adult tissue-derived stem/progenitor cells. [ABSTRACT FROM AUTHOR]

The article presents a systematic review of the population-based studies of infective endocarditis (IE). Fifteen population-based investigations with 2, 371 IE cases from seven countries from 1969 to 2000 were selected for the survey. The review determined that evidence from well-planned IE epidemiologic surveys is limited in many countries and suggest a changing distribution of underlying valvular heart disease in patients with IE and an increase in its surgical treatment.

The article reports on the results of a random-effect meta-analysis across eligible studies of the effectiveness of adult bone marrow (BM)-derived cells (BMC) in reducing infarct size and in enhancing left ventricular function and perfusion in the heart. Results indicated that therapy with BMCs appears to be safe and BMC transplantation offers modest improvements in physiologic and anatomic parameters in patients with both chronic ischemic heart disease and acute myocardial infarction.

Abstract: Adult stem cells from skeletal muscle (SM) have been shown to differentiate into multiple lineages. The impact of stem cell antigen-1 (Sca-1) expression on cardiomyogenic differentiation potential of SM-derived primitive cells remains unknown. Cardiomyogenic differentiation was induced in freshly isolated or culture-expanded Sca-1+/CD45−/c-kit−/Thy-1+ (SM+) and Sca1−/CD45−/c-kit−/Thy-1+ (SM−) cells isolated from SM of C57BL/6 mice. Expression of mRNA of cardiac-specific antigens and those associated with pluripotency was examined by real-time RT-PCR. Phenotypic analysis of expanded cells was performed during each passage by flow cytometry. Cardiomyocytic differentiation in vitro was verified by morphologic analysis, immunocytochemistry, and contractile properties. In freshly isolated cells, compared with unfractionated SM-derived cells as well as SM+ cells, mRNA expression of cardiac-specific antigens and those associated with cellular pluripotency was greater in SM− cells. Compared with SM− cells, SM+ cells exhibited greater expansion capacity. Freshly isolated SM− cells exhibited greater cardiac differentiation potential compared with freshly isolated SM+ cells (21.8±0.3% of SM− cells positive for cardiac markers vs. 9.1±0.7% of SM+ cells, P =0.00009). Differentiated SM− cells acquired a cardiomyocytic phenotype and exhibited spontaneous rhythmic contractions in vitro. The number of Sca-1+ cells in the SM− population increased markedly with time (0.9±0.1% in freshly isolated cells vs. 11.9±0.9% after the first passage vs. 99.0±0.6% after the second passage). This increase in Sca-1 expression was associated with a marked decline in the expression of cardiac markers following differentiation induction in culture-expanded SM− cells (21.8±0.3% in unexpanded cells vs. 16.6±1.3% after the first passage vs. 6.0±0.5% after the second passage, P =0.00001 vs. unexpanded cells). In contrast, the SM+ cells did not exhibit any consistent pattern in either phenotypic or differentiation capability with expansion. We conclude that SM− cells are inherently predisposed to undergo cardiac differentiation and are enriched in markers of pluripotency. While both Sca-1+ and Sca-1− primitive cells from SM can undergo cardiac differentiation, Sca-1− cells exhibit greater cardiomyogenic potential, and the appearance of Sca-1 during expansion is associated with a decline in cardiac differentiation plasticity. [Copyright &y& Elsevier]

Background: The application of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in contemporary management of cardiogenic shock (CS) has dramatically increased. Despite increased utilization, few predictive models exist to estimate patient survival based on pre-ECMO characteristics. Furthermore, the prognostic implications of pre-ECMO cardiac arrest are not well defined. Methods: Utilizing an institutional VA-ECMO database, all consecutive patients undergoing VA-ECMO for the management of CS from January 1, 2014, to July 1, 2019, were identified. Survival to hospital discharge was analyzed based on cannulation indication in patients with and without pre-ECMO cardiac arrest. Patients who received extracorporeal cardiopulmonary resuscitation (eCPR) were analyzed separately. Results: Of the 214 patients identified, 110 did not suffer a cardiac arrest prior to cannulation (cohort 1), 57 patients had a cardiac arrest with sustained ROSC (cohort 2), and 47 were cannulated as a component of eCPR (cohort 3). Despite sustained ROSC (cohort 2), the presence of pre-ECMO cardiac arrest was associated with a significant reduction in survival to hospital discharge (22.8% vs. 55.5% in cohort 1; p < 0.001). Comparatively, survival to discharge was similar in patients undergoing eCPR (22.8% vs. 17.0%; p = 0.464). Finally, patients with a cardiac arrest were significantly more likely to have a neurological etiology death with VA-ECMO than patients supported prior to hemodynamic collapse (18.3% vs. 2.7%; p < 0.001). This result is seen in those with sustained ROSC (21.1% vs. 2.7%; p < 0.001) and those with eCPR (14.9% vs. 2.7%; p = 0.004). Conclusion: In our cohort, pre-ECMO cardiac arrest carries a negative prognostic value across all indications and is associated with an increased prevalence of neurological-etiology death. This finding is true in patients with sustained ROSC as well as those resuscitated with eCPR. Cardiac arrest can inform survival probability with VA-ECMO as early implementation of VA-ECMO may mitigate adverse outcomes in patients at the highest risk of hemodynamic collapse. [ABSTRACT FROM AUTHOR]

Myocardial infarction (MI) triggers a complex inflammatory response that is essential for cardiac repair but can also lead to adverse outcomes if left uncontrolled. Recent studies have highlighted the importance of epigenetic modifications in regulating post-MI inflammation. This study investigated the role of the autotaxin (ATX)/lysophosphatidic acid (LPA) signaling axis in modulating myocardial inflammation through epigenetic pathways in a mouse model of MI. C57BL/6 J mice underwent left anterior descending coronary artery ligation to induce MI and were treated with the ATX inhibitor, PF-8380, or vehicle. Cardiac tissue from the border zone was collected at 6 h, 1, 3, and 7 days post-MI for epigenetic gene profiling using RT2 Profiler PCR Arrays. The results revealed distinct gene expression patterns across sham, MI + Vehicle, and MI + PF-8380 groups. PF-8380 treatment significantly altered the expression of genes involved in inflammation, stress response, and epigenetic regulation compared to the vehicle group. Notably, PF-8380 downregulated Hdac5, Prmt5, and Prmt6, which are linked to exacerbated inflammatory responses, as early as 6 h post-MI. Furthermore, PF-8380 attenuated the reduction of Smyd1, a gene important in myogenic differentiation, at 7 days post-MI. This study demonstrates that the ATX/LPA signaling axis plays a pivotal role in modulating post-MI inflammation via epigenetic pathways. Targeting ATX/LPA signaling may represent a novel therapeutic strategy to control inflammation and improve outcomes after MI. Further research is needed to validate these findings in preclinical and clinical settings and to elucidate the complex interplay between epigenetic mechanisms and ATX/LPA signaling in the context of MI. [ABSTRACT FROM AUTHOR]

In the article, the author discusses the prevention of platelet thrombosis with protease-activated receptor (PAR) 1 Pepducin. Platelet arterial thrombosis occurs after atherosclerotic plaque rupture, erosion and percutaneous coronary interventions (PCI) is the cause of myocardial infarctions and many ischemic strokes. protease-activated receptor (PAR) 1 when cleaved by thrombin triggers intracellular signaling events resulting in secretion of granule contents including ADP.

Elevated neutrophil count is associated with higher risk of major adverse cardiac events including myocardial infarction and early development of heart failure. Neutrophils contribute to cardiac damage through a number of mechanisms, including attraction of other immune cells and release of inflammatory mediators. Recently, a number of independent studies have reported a causal role for neutrophil-derived alarmins (i.e. S100A8/A9) in inducing inflammation and cardiac injury following myocardial infarction (MI). Furthermore, a positive correlation between serum S100A8/A9 levels and major adverse cardiac events (MACE) in MI patients was also observed implying that targeting neutrophils or their inflammatory cargo could be beneficial in reducing heart failure. However, contradictory to this idea, neutrophils and neutrophil-derived S100A8/A9 also seem to play a vital role in the resolution of inflammation. Thus, a better understanding of how neutrophils balance these seemingly contrasting functions would allow us to develop effective therapies that preserve the inflammation-resolving function while restricting the damage caused by inflammation. In this review, we specifically discuss the mechanisms behind neutrophil-derived S100A8/A9 in promoting inflammation and resolution in the context of MI. We also provide a perspective on how neutrophils could be potentially targeted to ameliorate cardiac inflammation and the ensuing damage. [ABSTRACT FROM AUTHOR]

An editorial is presented which argues against the optimal revascularization threshold of fractional flow reserve (FFR) and outcomes from high-volume center in China. Topics include percutaneous coronary intervention (PCI) has achieving complete revascularization, in patients with multivessel disease; and less invasive techniques have developed to determine FFR from computed tomography angiography without a pressure wire.

The article focuses on the results of the TAILOR-PCI randomized study examining a clinical decision strategy that depends on CYP2C19 genotyping to guide antiplatelet drug assignment following percutaneous coronary interventions. Study subjects received clopidogrel without initial genetic testing while another group of subjects received clopidogrel versus ticagrelor or prasugel. It suggests the use of a personalized medicine approach that involved genotyping for therapeutic interventions.

Circulating monocytes have different subsets, including classical (CD14++CD16−), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++), which play different roles in cardiovascular physiology and disease progression. The predictive value of each subset for adverse clinical outcomes in patients with coronary artery disease is not fully understood. We sought to evaluate the prognostic efficacy of each monocyte subset in patients with ST-elevation myocardial infarction (STEMI). We recruited 100 patients with STEMI who underwent primary percutaneous coronary intervention (PCI). Blood samples were collected at the time of presentation to the hospital (within 6 h from onset of symptoms, baseline (BL)) and then at 3, 6, 12, and 24 h after presentation. Monocytes were defined as CD45+/HLA-DR+ and then subdivided based on the expression of CD14, CD16, CCR2, CD11b, and CD42. The primary endpoint was a composite of all-cause death, hospitalization for heart failure, stent thrombosis, in-stent restenosis, and recurrent myocardial infarction. Univariate and multivariate Cox proportional hazards models, including baseline comorbidities, were performed. The mean age of our cohort was 58.9 years and 25% of our patients were females. Patients with high levels (above the median) of CD14+CD16++ monocytes showed an increased risk for the primary endpoint in comparison to patients with low levels; adjusted hazard ratio (aHR) for CD14+/CD16++ cells was 4.3 (95% confidence interval (95% CI) 1.2–14.8, p = 0.02), for CD14+/CD16++/CCR2+ cells was 3.82 (95% CI 1.06–13.7, p = 0.04), for CD14+/CD16++/CD42b+ cells was 3.37 (95% CI 1.07–10.6, p = 0.03), for CD14+/CD16++/CD11b+ was 5.17 (95% CI 1.4–18.0, p = 0.009), and for CD14+ HLA-DR+ was 7.5 (95% CI 2.0–28.5, p = 0.002). CD14++CD16−, CD14++CD16+, and their CD11b+, CCR2+, and CD42b+ aggregates were not significantly predictive for our composite endpoint. Our study shows that CD14+ CD16++ monocytes and their subsets expressing CCR2, CD42, and CD11b could be important predictors of clinical outcomes in patients with STEMI. Further studies with a larger sample size and different coronary artery disease phenotypes are needed to verify the findings. [ABSTRACT FROM AUTHOR]

Elevated C-reactive protein (CRP) levels are an indicator of inflammation, a major risk factor for cardiovascular disease (CVD). However, this potential association in observational studies remains inconclusive. We performed a two-sample bidirectional Mendelian randomization (MR) study using publicly available GWAS summary statistics to evaluate the relationship between CRP and CVD. Instrumental variables (IVs) were carefully selected, and multiple approaches were used to make robust conclusions. Horizontal pleiotropy and heterogeneity were evaluated using the MR-Egger intercept and Cochran's Q-test. The strength of the IVs was determined using F-statistics. The causal effect of CRP on the risk of hypertensive heart disease (HHD) was statistically significant, but we did not observe a significant causal relationship between CRP and the risk of myocardial infarction, coronary artery disease, heart failure, or atherosclerosis. Our primary analyses, after performing outlier correction using MR-PRESSO and the Multivariable MR method, revealed that IVs that increased CRP levels also increased the HHD risk. However, after excluding outlier IVs identified using PhenoScanner, the initial MR results were altered, but the sensitivity analyses remained congruent with the results from the primary analyses. We found no evidence of reverse causation between CVD and CRP. Our findings warrant updated MR studies to confirm the role of CRP as a clinical biomarker for HHD. [ABSTRACT FROM AUTHOR]

Migration and bone marrow (BM) homing of hematopoietic stem progenitor cells (HSPCs) is regulated by several signaling pathways, and here we provide evidence for the involvement in this process of hematopoietic-specific phospholipase C-β2 (PLC-β2). This enzyme is involved in release of intracellular calcium and activation of protein kinase C (PKC). Recently we reported that PLC-β2 promotes mobilization of HSPCs from BM into peripheral blood (PB), and this effect is mediated by the involvement of PLC-β2 in the release of proteolytic enzymes from granulocytes and its role in disintegration of membrane lipid rafts. Here we report that, besides the role of PLC-β2 in the release of HSPCs from BM niches, PLC-β2 regulates the migration of HSPCs in response to chemotactic gradients of BM homing factors, including SDF-1, S1P, C1P, and ATP. Specifically, HSPCs from PLC-β2-KO mice show impaired homing and engraftment in vivo after transplantation into lethally irradiated mice. This decrease in migration of HSPCs can be explained by impaired calcium release in PLC-β2-KO mice and a high baseline level of heme oxygenase 1 (HO-1), an enzyme that negatively regulates cell migration. [ABSTRACT FROM AUTHOR]

Objective: The ischemic myocardium releases multiple chemotactic factors responsible for the mobilization and recruitment of bone marrow−derived cells to injured myocardium. However, the mobilization of primitive pluripotent stem cells (PSCs) enriched in very small embryonic-like stem cells (VSELs) in various cardiac ischemic scenarios is not well understood. Materials and Methods: Fifty-four ischemic heart disease patients, including subjects with stable angina, non−ST elevation myocardial infarction, and ST elevation myocardial infarction (STEMI) and 12 matched controls were enrolled. The absolute numbers of circulating stem/primitive cells in samples of peripheral blood (PB) were quantitated by ImageStream analysis and conventional flow cytometry. Gene expression of PSC (Oct-4 and Nanog), early cardiomyocyte (Nkx-2.5 and GATA-4), and endothelial (von Willebrand factor) markers was analyzed by real-time polymerase chain reaction. Results: The absolute numbers of PSCs, stem cell populations enriched in VSELs, and hematopoietic stem cells present in PB were significantly higher in STEMI patients at presentation and declined over time. There was a corresponding increase in pluripotent, cardiac, and endothelial gene expression in unfractionated PB cells and sorted PB-derived primitive CD34+ cells. The absolute numbers of circulating VSELs and hematopoietic stem cells in STEMI correlated negatively with patient age. Conclusions: Myocardial ischemia mobilizes primitive PSCs including pluripotent VSELs into the circulation. The peak of mobilization occurs within 12 hours in patients presenting with STEMI, which may represent a therapeutic window for future clinical applications. Reduced stem cell mobilization with advancing age could explain, in part, the observation that age is associated with poor prognosis in patients with myocardial infarction. [ABSTRACT FROM AUTHOR]

Background: Ischemic heart disease, often caused by an acute myocardial infarction (AMI) is one of the leading causes of morbidity and mortality worldwide. Despite significant advances in medical and procedural therapies, millions of AMI patients progress to develop heart failure every year. Methods: Here, we examine the combination therapy of human mesenchymal stromal cells (MSCs) and endothelial colony-forming cells (ECFCs) to reduce the early ischemic damage (MSCs) and enhance angiogenesis (ECFCs) in a pre-clinical model of acute myocardial infarction. NOD/SCID mice were subjected to AMI followed by transplantation of MSCs and ECFCs either alone or in combination. Cardiomyocyte apoptosis and cardiac functional recovery were assessed in short- and long-term follow-up studies. Results: At 1 day after AMI, MSC- and ECFC-treated animals demonstrated significantly lower cardiomyocyte apoptosis compared to vehicle-treated animals. This phenomenon was associated with a significant reduction in infarct size, cardiac fibrosis, and improvement in functional cardiac recovery 4 weeks after AMI. Conclusions: The use of ECFCs, MSCs, and the combination of both cell types reduce cardiomyocyte apoptosis, scar size, and adverse cardiac remodeling, compared to vehicle, in a pre-clinical model of AMI. These results support the use of this combined cell therapy approach in future human studies during the acute phase of ischemic cardiac injury. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) results in weakening of the heart muscle and an increased risk for chronic heart failure. Therapeutic stem cells have been shown to reduce inflammatory signaling and scar tissue expansion, despite most of these studies being limited by poor retention of cells. Gelatin methacrylate (GelMA) coatings have been shown to increase the retention of these therapeutic cells near the infarct. In this work, we evaluate two different potential binding partners for GelMA-coated bone marrow cells (BMCs) and myocardial tissue: the extracellular matrix (ECM) and interstitial non-cardiomyocytes. While cells containing β1 integrins mediate cell-ECM adhesion in vivo, these cells do not promote binding to our collagen-degraded, GelMA coating. Specifically, microscopic imagining shows that even with high integrin expression, GelMA-coated BMCs do not bind to cells within the myocardium. Alternatively, BMC incubation with decellularized heart tissue results in higher adhesion of coated cells versus uncoated cells supporting our GelMA-ECM binding mode. To further evaluate the ECM binding mode, cells were incubated on slides modified with one of three different major heart ECM components: collagen, laminin, or fibronectin. While all three components promoted higher adhesion than unmodified glass, collagen-coated slides resulted in a significantly higher adhesion of GelMA-coated BMCs over laminin and fibronectin. Incubation with unmodified BMCs confirmed that without a GelMA coating minimal adhesion of BMCs occurred. We conclude that GelMA cellular coatings significantly increase the binding of cells to collagen within the ECM. Our results provide progress towards a biocompatible and easily translatable method to enhance the retention of transplanted cells in human studies. [ABSTRACT FROM AUTHOR]

Background: Individuals waking from general anesthesia frequently experience disagreeable symptoms of catheterrelated bladder discomfort (CRBD) due to intraoperative catheterization. Objective: Comparing efficacy of nefopam versus tramadol to prevent (CRBD) after percutaneous nephrolithotomy (PCNL) surgery. Patients and methods: This was a prospective double-blind study conducted on a total of 150 adult patients between the ages of 18 and 60, of both sexes, who were undergoing percutaneous nephrolithotomy (PCNL) for a renal upper ureteric stone. They were divided into three groups; Tramadol group, Nefopam group and Control group. Results: The demographic data showed no statistically significant differences between the three groups (P value >0.05). Average fentanyl use after surgery was much higher in the control group (326.50±35.14 mcg/24 hours) compared with both tramadol (165.00±15.15 mcg/24 hours) and nefopam groups (183.00±21.69 mcg/24 hours) (P value <0.001). The severity of CRBD, when comparing the control group to the tramadol and nefopam groups, the control group had significantly higher post-operative pain and rescue analgesic use throughout all study timeframes (P value <0.05). Sedation, an increase in the number of patients reporting post-operative nausea and vomiting (PONV), and dry mouth were all significantly more common in the tramadol group than in the nefopam or control groups (P value<0.05). Conclusions: Intra-operative administration of both tramadol and nefopam significantly reduced post-operative CRBD, pain together with reduced consumption of post-operative fentanyl requirements in patients undergoing PCNL. However, nefopam was superior to tramadol as it was not associated with post-operative sedation and had lesser incidence of post-operative adverse events. [ABSTRACT FROM AUTHOR]

Aim To evaluate how micropulse transscleral diode laser cyclophotocoagulation (MP-TSCPC) is a safe and effective procedure, in reducing intraocular pressure (IOP) in different glaucoma patients among the Egyptian population. Study design Prospective, noncomparative interventional study. Patients and methods This study assessed the effect of MP-TSCPC laser on patients with different types of glaucoma. Forty eyes of 40 patients were included in our study. Patients were recruited from Benha University Hospital and Egyptian Eye Academy, and the procedure was done during the period between January 2020 and July 2021. Results The mean±SD baseline IOP was 27.72±8.6 mmHg, which showed significant reduction at postsurgical month 6, becoming 16.28±6.38 mmHg (P=0.001). The mean number of IOP-lowering agents was 2.35±1.03 preoperatively, which dropped significantly to 1.50±1.24 at 6 months. Postoperative logMAR best-corrected visual acuity was not significantly reduced from baseline. There was no development of significant postoperative complications. Conclusion MP-TSCPC is an efficient, safe, and simple technique with promising results in lowering IOP and can be used in patients with different types of glaucoma. [ABSTRACT FROM AUTHOR]

Objectives: This study sought to assess the efficacy of angiotensin-converting enzyme inhibitors (ACEIs) in patients with coronary heart disease and preserved left ventricular (LV) function. Background: The ACEIs have been shown to improve outcomes in patients with heart failure and myocardial infarction (MI). However, there is conflicting evidence concerning the benefits of ACEIs in patients with coronary artery disease (CAD) and preserved LV systolic function. Methods: An extensive search was performed to identify randomized, placebo-controlled trials of ACEI use in patients with CAD and preserved LV systolic function. Of 61 potentially relevant articles screened, 6 trials met the inclusion criteria. They were reviewed to determine cardiovascular mortality, nonfatal MI, all-cause mortality, and revascularization rates. We performed random-effect model meta-analyses and quantified between-studies heterogeneity with I2. Results: There were 16,772 patients randomized to ACEI and 16,728 patients randomized to placebo. Use of ACEIs was associated with a decrease in cardiovascular mortality (relative risk [RR] 0.83, 95% confidence interval [CI] 0.72 to 0.96, p = 0.01), nonfatal MI (RR 0.84, 95% CI 0.75 to 0.94, p = 0.003), all-cause mortality (RR 0.87, 95% CI 0.81 to 0.94, p = 0.0003), and revascularization rates (RR 0.93, 95% CI 0.87 to 1.00, p = 0.04). There was no significant between-studies heterogeneity. Treatment of 100 patients for an average duration of 4.4 years prevents either of the adverse outcomes (one death, or one nonfatal myocardial infarction, or one cardiovascular death or one coronary revascularization procedure). Conclusions: The cumulative evidence provided by this meta-analysis shows a modest favorable effect of ACEIs on the outcome of patients with CAD and preserved LV systolic function. [Copyright &y& Elsevier]

An experimental investigation has been performed to study the heat transfer, fluid flow and pressure drop characteristics of longitudinal rectangular-fin array for three different orientations of the tested model in the flow field: (i) parallel flow, (ii) impinging flow, and (iii) reverse impinging flow, to determine the optimal position for the fin array in the flow field. During the experiments, all fin array geometries were fixed. Air was the working fluid with Prandtl number 0.7. The flow regime was turbulent and the Reynolds number ranged from 7 × 104 to 5 × 105 based on the test section hydraulic diameter. The flow entered the tested section with uniform velocity and temperature profiles, and the flow pattern around the tested model was visualized. In general, it was found that for the three orientations of the tested model in the fluid flow, the parallel flow case yielded the highest heat transfer rate and the lowest pressure drop followed by the impinging flow then the reverse impinging flow cases. [Copyright &y& Elsevier]

The effects of the fin arrays geometries and also the fin tip-to-shroud clearance on the heat transfer, the fluid flow and the pressure drop characteristics of longitudinal rectangular-fin arrays have been investigated. During the experiments, different geometrical parameters were varied such as the fin height (H), the fin thickness (t), the inter-fin space (W), the fins number and the fin tip-to-shroud clearance (C) was varied parametrically; starting with the no-clearance case. Two shroud types were used (one plain and the other is equipped with wires coil as modified shroud). The heat transfer coefficient corresponding to the presence and absence of clearance were compared under the condition of equal airflow rate. Air is the working fluid, the flow regime is turbulent, and the flow pattern around the tested models was visualized. It was found that the axial pressure drop along the tested model is increased as the flow travels in the inter-fin region deeply in the stream-wise (X) direction, with increasing the fin height, the Reynolds number, and with decreasing the inter-fin space and the fin thickness. The tested model-mean Nusselt number (Num) increases with increasing the Reynolds number, the inter-fin space, and the fin thickness and with decreasing the fin height. Increasing the clearance between the fin tip-to-shroud decreases the tested model-mean Nusselt number and at certain clearance to fin height ratio (C/H)=1.25, the effect of the fin tips plain shroud goes off. It was also found that the tested model with the modified shroud (equipped with wire coil) gives higher mean Nusselt number than that with the plain shroud, and at certain clearance to fin height ratio (C/H)=1, the effect of the wire coil goes off. Eleven empirical equations are derived to correlate the mean Nusselt number as a function of the Reynolds number and other experimental variable parameters individual, fin thickness, fin height, inter-fin space and shroud clearance to fin height ratio. Finally the present work general empirical formula is given in the formNum=5.734146(ReL)0.42422W/L0.214171H/W−0.36263t/W0.214171H/W−0.36263t/W−0.36263t/W0.15250885where 24,649&les;ReL&les;189,462, 3 mm&les;t&les;9 mm, 23 mm&les;H&les;92 mm, 10 mm&les;W&les;42 mm and L=150 mm. [Copyright &y& Elsevier]

Novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2. The virus causes an exaggerated immune response, resulting in a cytokine storm and acute respiratory distress syndrome, the leading cause of COVID-19-related mortality and morbidity. So far, no therapies have succeeded in circumventing the exacerbated immune response or cytokine storm associated with COVID-19. Mesenchymal stem cells (MSCs), through their immunomodulatory and regenerative activities, mostly mediated by their paracrine effect and extracellular vesicle production, have therapeutic potential in many autoimmune, inflammatory, and degenerative diseases. In this paper, we review clinical studies on the use of MSCs for COVID-19 treatment, including the salutary effects of MSCs on the pathophysiology of COVID-19 and the immunomodulation of the cytokine storm. Ongoing clinical trial designs, cell sources, dose and administration, and populations are summarized, and the paracrine mode of benefit is discussed. We also offer suggestions for optimizing MSC-based therapies, including genetic engineering, strategies for cell surface modification, nanotechnology applications, and combination therapies. [ABSTRACT FROM AUTHOR]

Introduction and Hypothesis. The role of inflammation is widely recognized in the pathogenesis of coronary artery disease. Research on animal models had shown the potential benefits of targeting specific inflammatory pathways. However, studies on human subjects are limited with small number of patients and no head-to-head comparisons. Methods. We conducted a network meta-analysis of randomized controlled trials that studied the effects of anti-inflammatory medications on cardiovascular outcomes of coronary artery disease patients. We searched the electronic database until March 2020 for relevant studies. Results. Nineteen trials examining the efficacy of eight anti-inflammatory medications (pexelizumab, anakinra, colchicine, darapladib, varespladib, canakinumab, inclacumab, and losmapimod) were selected for analysis. Overall, there is no statistically significant difference in all-cause mortality, cardiovascular mortality, revascularization, and major cardio and cerebrovascular events (MACCE) with the use of anti-inflammatory drugs. However, we found the use of colchicine significantly reduces the odds of developing stroke by approximately 75% (OR 0.26, CI 0.10-0.63). Colchicine use was also associated with a lower risk of revascularization and MACCE compared to the other agents. Our subgroup analyses comparing the timing of medication initiation (within 7 days vs. >7 days) and clinical presentation (ACS vs. non-ACS) revealed a significant reduction in the risk of recurrent MI in the group that received medication after seven days (OR 0.92, CI 0.86-0.99) and the non-ACS group (OR 0.88, CI 0.80-0.98). Conclusion. Although many anti-inflammatory medications have failed to reduce adverse cardiovascular outcomes in the CAD population, selected medications show promise among subgroups of patients without ACS or after the first week following an acute ischemic event. Future studies examining the proper timing and targetable anti-inflammatory pathways are warranted. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) initiates pathological inflammation which aggravates tissue damage and causes heart failure. Lysophosphatidic acid (LPA), produced by autotaxin (ATX), promotes inflammation and the development of atherosclerosis. The role of ATX/LPA signaling nexus in cardiac inflammation and resulting adverse cardiac remodeling is poorly understood. We assessed autotaxin activity and LPA levels in relation to cardiac and systemic inflammation in AMI patients and C57BL/6 (WT) mice. Human and murine peripheral blood and cardiac tissue samples showed elevated levels of ATX activity, LPA, and inflammatory cells following AMI and there was strong correlation between LPA levels and circulating inflammatory cells. In a gain of function model, lipid phosphate phosphatase-3 (LPP3) specific inducible knock out (Mx1-Plpp 3 Δ) showed higher systemic and cardiac inflammation after AMI compared to littermate controls (Mx1-Plpp3fl/fl); and a corresponding increase in bone marrow progenitor cell count and proliferation. Moreover, in Mx1- Plpp3Δ mice, cardiac functional recovery was reduced with corresponding increases in adverse cardiac remodeling and scar size (as assessed by echocardiography and Masson's Trichrome staining). To examine the effect of ATX/LPA nexus inhibition, we treated WT mice with the specific pharmacological inhibitor, PF8380, twice a day for 7 days post AMI. Inhibition of the ATX/LPA signaling nexus resulted in significant reduction in post-AMI inflammatory response, leading to favorable cardiac functional recovery, reduced scar size and enhanced angiogenesis. ATX/LPA signaling nexus plays an important role in modulating inflammation after AMI and targeting this mechanism represents a novel therapeutic target for patients presenting with acute myocardial injury. Schematic summarizing the role of autotaxin/lysophosphatidic acid signaling in post-AMI inflammation and cardiac dysfunction. Damage associated molecular pattern molecules released from dying cardiomyocytes and cardiac fibroblasts initiate an inflammatory cascade resulting in the activation of Autotaxin/lysophosphatidic acid signaling; which in turn augments local and systemic inflammation through the release of inflammatory cytokines and chemokines. Systemically, activation of bone marrow progenitors results in increased production of inflammatory cells. Locally, increased chemoattractants such as MCP-1 results in increased infiltration of inflammatory cells to the damaged myocardium. Collectively, these events result in prolonged and exacerbated inflammatory response and impaired cardiac functional recovery Unlabelled Image • LPA-ATX signaling nexus modulated post-myocardial infarction inflammation. • Pharmacological inhibition of ATX/LPA signaling attenuates cardiac and systemic inflammation post-AMI. • ATX inhibition post-AMI enhances cardiac recovery, reduces adverse remodeling and scar size. [ABSTRACT FROM AUTHOR]

Background: Medically ill patients remain at risk of venous thromboembolism for up to 6 weeks after hospital discharge due to factors such as immobilization and inflammation.Methods: We conducted a meta-analysis and systematic review of Phase III randomized controlled trials comparing extended use of direct oral anticoagulation (DOAC) post discharge for venous thromboembolism prophylaxis with placebo.Results: The primary efficacy outcome (composite of venous thromboembolism and mortality) occurred in 373/13,099 patients in the DOAC group (2.9%) and 477/13,309 patients in the placebo group (3.6%), with an odds ratio (OR) of 0.79 (95% confidence interval [CI], 0.69-0.91). The secondary efficacy outcome (nonfatal symptomatic venous thromboembolism) occurred in 75/15,573 patients in the DOAC group (0.48%) and 120/15,599 in the placebo group (0.77%) with an OR of 0.62 (95% CI, 0.47-0.83). The primary safety outcome (major bleeding) occurred in 90/15,474 patients in the DOAC group (0.58%) and in 47/15,418 patients in the placebo group (0.3%) with an OR of 1.92 (95% CI, 1.35-2.73). The secondary safety (clinically relevant nonmajor bleeding) outcome occurred in 333/15,474 patients in the DOAC group (2.2%) and 191/15,418 patients in the placebo group (1.2%) with an OR of 1.75 (95% CI, 1.46-2.1). The extended use of venous thromboembolism prophylaxis post discharge results in decreased venous thromboembolism events but increased bleeding risk. Our cost-effective analysis of extended DOAC use vs placebo showed superiority of the DOAC group.Conclusion: In conclusion, given the mortality benefit and cost benefit, extended thromboprophylaxis is a beneficial strategy to efficiently reduce the risk of venous thromboembolism. [ABSTRACT FROM AUTHOR]

Introduction: Acute myocardial infarction (AMI) and resulting cardiac damage and heart failure are leading causes of morbidity and mortality worldwide. Multiple studies have examined the utility of CD34+ cells for the treatment of acute and ischemic heart disease. However, the optimal strategy to enrich CD34 cells from clinical sources is not known. We examined the efficacy of fluorescence activated cell sorting (FACS) and magnetic beads cell sorting (MACS) methods for CD34 cell isolation from mobilized human mononuclear peripheral blood cells (mhPBMNCs). Methods: mhPBCs were processed following acquisition using FACS or MACS according to clinically established protocols. Cell viability, CD34 cell purity and characterization of surface marker expression were assessed using a flow cytometer. For in vivo characterization of cardiac repair, we conducted LAD ligation surgery on 8–10 weeks female NOD/SCID mice followed by intramyocardial transplantation of unselected mhPBMNCs, FACS or MACS enriched CD34+ cells. Results: Both MACS and FACS isolation methods achieved high purity rates, viability, and enrichment of CD34+ cells. In vivo studies following myocardial infarction demonstrated retention of CD34+ in the peri-infarct region for up to 30 days after transplantation. Retained CD34+ cells were associated with enhanced angiogenesis and reduced inflammation compared to unselected mhPBMNCs or PBS treatment arms. Cardiac scar and fibrosis as assessed by immunohistochemistry were reduced in FACS and MACS CD34+ treatment groups. Finally, reduced scar and augmented angiogenesis resulted in improved cardiac functional recovery, both on the global and regional function and remodeling assessments by echocardiography. Conclusion: Cell based therapy using enriched CD34+ cells sorted by FACS or MACS result in better cardiac recovery after ischemic injury compared to unselected mhPBMNCs. Both enrichment techniques offer excellent recovery and purity and can be equally used for clinical applications. [ABSTRACT FROM AUTHOR]

Very Small Embryonic-Like (VSEL) stem cells are a proposed pluripotent population, residing in adult tissues. VSELs have been described in multiple tissues including bone marrow, cord blood, and gonads. They exhibit multiple characteristics of embryonic stem cells including the ability to differentiate into cellular lineages of all three germ layers, including cardiomyocytes and vascular endothelial cells. However, their presence in adult solid organs such as heart in humans has not been established. VSELs are valuable source of stem cells for tissue regeneration and replacement of cells for turnover and usual wear-and-tear. The purpose of our study was to explore the existence of human VSELs (huVSELs) in human heart tissue and examine the changes in their prevalence with aging and cardiac disease. Human heart tissue, collected from healthy and ischemic heart disease subjects was examined for the prevalence of VSELS, defined as CD45-/CD133+/SSEA4+. Both epicardial and endocardial tissues were examined comparing VSEL numbers across different age groups. Our data confirm the existence of huVSELs in adult hearts with decreasing prevalence during aging. This is the first evidence of huVSELs in adult cardiac tissue. Cardiac huVSELs could be further explored in future studies to characterize their primitive potential and therapeutic potential in regenerative studies. [ABSTRACT FROM AUTHOR]

Introduction: Previous studies have reported lower rates of coronary angiography and revascularization, and significantly higher mortality among patients infected with human immunodeficiency virus (HIV) presenting with acute myocardial infarction (AMI). This observational study was designed to evaluate characteristics and inpatient outcomes of patients with seropositive HIV infection presenting with AMI.Methods: Using the National Inpatient Sample (NIS) database, we identified patients (admissions) with a primary diagnosis of myocardial infarction and a co-occurring HIV. We described baseline characteristics and outcomes. Our primary outcomes of interest were prevalence of coronary angiography, revascularization (percutaneous coronary intervention (PCI) or CABG), and mortality.Results: From 2010 to 2014, of about 2,977,387 patients with a primary diagnosis of AMI, 10,907 (0.4%) were HIV seropositive. Patients with HIV were younger and more likely to be African American or Hispanic. Coronary angiography and revascularization were performed more frequently in the HIV population. The higher prevalence of revascularization was driven by a higher incidence of PCI. In a multivariable model, patients with HIV were no more likely to undergo revascularization than the general population. This was also the case for PCI. Unadjusted all-cause mortality was lower among patients with HIV. After controlling for confounders, this finding was not significant (OR 0.97, 95% CI 0.75-1.25, p = 0.79). The length of stay between both groups was comparable.Conclusion: In this current analysis, we did not note any treatment bias or difference in the rate of in-hospital total mortality for HIV-seropositive patients presenting with AMI compared with the general population. [ABSTRACT FROM AUTHOR]

Objective: To identify the predictor factors of left ventricular (LV) dysfunction following patent ductus arteriosus (PDA) surgical ligation.Background: PDA is viewed as a noticeable amongst the most widely recognized congenital heart defects in children and its closure is responsible for many hemodynamic changes that require intervention and care.Methods: A retrospective study included fifty children with isolated PDA treated by surgical ligation from June 2015 to June 2018. The LV dimensions and systolic function were assessed by two-dimensional echocardiography pre and post PDA ligation. All cases were followed-up on the first-day, 1 month and 6 months post ligation.Results: The mean age of cases was 15.78 ± 7.58 months and 72% were females. The mean duct size was 4.08 ± 1.25 mm. There was a marked decrease in LVEDd, LA/Ao, EF and FS in the first-day post ligation contrasted with pre ligation values. Moreover, an amazing decline in LVEDd and LA/Ao ratio was observed 1 month post ligation contrasted with the early post ligation status with asynchronous improvement of FS and EF at one and 6 months postoperatively.Conclusion: PDA ligation is associated with a noteworthy LV systolic dysfunction within the first day post ligation; that in a significant number of patients may require anti-failure measures, prolong the hospital stay and necessitate a regular follow up and monitoring of LV function. PDA size, age, preoperative LVEDd and FS can be considered as predictor factors for suspicion of acute decrease in the LV systolic function early post PDA ligation.Trial Registration: ClinTrial.Gov NCT04018079 . [ABSTRACT FROM AUTHOR]

The optimal treatment strategy for coronary chronic total occlusion (CTO) has not been well established. The benefit of percutaneous coronary intervention (PCI) was inferred mainly from observational studies comparing successful versus failed PCI without a control group receiving optimal medical therapy (OMT). We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies comparing PCI using drug-eluting stent (DES) versus OMT alone in patients with CTO. Eight studies were identified: 3 RCTs and 5 observational studies. Among a total of 4784 included patients, 2461 patients underwent PCI and 2323 patients received OMT. There was a significant association between PCI and lower cardiac mortality (odds ratio = 0.62; 95% confidence interval 0.42-0.93; P =.02). There was no significant difference between PCI and OMT regarding major adverse cardiac events, recurrent myocardial infarction (MI), repeat revascularization, or stroke. In the RCT subset (1399 patients), there was no significant difference between PCI and OMT regarding clinical outcomes. Compared with OMT alone, PCI with DES for CTO was associated with lower cardiac mortality, mainly driven by observational studies, without significant difference in recurrent MI or repeated revascularization. Further RCTs are needed to investigate the role of PCI for management of patients with CTO. [ABSTRACT FROM AUTHOR]

Background. Myocardial inflammation following acute ischemic injury has been linked to poor cardiac remodeling and heart failure. Many studies have linked myeloperoxidase (MPO), a neutrophil and inflammatory marker, to cardiac inflammation in the setting of acute coronary syndrome (ACS). However, the prognostic role of MPO for adverse clinical outcomes in ACS patients has not been well established. Methods. MEDLINE and Cochrane databases were searched for studies from 1975 to March 2018 that investigated the prognostic value of serum MPO in ACS patients. Studies which have dichotomized patients into a high MPO group and a low MPO group reported clinical outcomes accordingly and followed up patients for at least 30 days to be eligible for enrollment. Data were analyzed using random-effects model. Sensitivity analyses were conducted for quality control. Results. Our meta-analysis included 13 studies with 9090 subjects and a median follow-up of 11.4 months. High MPO level significantly predicted mortality (odds ratio (OR) 2.03; 95% confidence interval (CI): 1.40-2.94; P<0.001), whereas it was not significantly predictive of major adverse cardiac events and recurrent myocardial infarction (MI) (OR 1.28; CI: 0.92-1.77, P=0.14 and OR 1.23; CI: 0.96-1.58, P=0.101, respectively). Hypertension, diabetes mellitus, and age did not affect the prognostic value of MPO for clinical outcomes, whereas female gender and smoking status have a strong influence on the prognostic value of MPO in terms of mortality and recurrent MI (metaregression coefficient -8.616: 95% CI -14.59 to -2.633, P=0.0048 and 4.88: 95% CI 0.756 to 9.0133, P=0.0204, respectively). Conclusions. Our meta-analysis suggests that high MPO levels are associated with the risk of mortality and that MPO can be incorporated in risk stratification models that guide therapy of high-risk ACS patients. [ABSTRACT FROM AUTHOR]

Mobilization of stem cells from bone marrow (BM) into peripheral blood (PB) in response to tissue or organ injury, infections, strenuous exercise, or mobilization-inducing drugs is as we postulated result of a "sterile inflammation" in the BM microenvironment that triggers activation of the Complement Cascade (ComC). Therefore, we became interested in the role of the Nlrp3 inflammasome in this process and show for the first time that its activation in ATP-dependent manner orchestrates BM egress of hematopoietic stem/progenitor cells (HSPCs) as well as other stem cells, including mesenchymal stroma cells (MSCs), endothelial progenitor cells (EPCs), and very small embryonic-like stem cells (VSELs). To explain this extracellular ATP is a potent activator of the Nrlp3 inflammasome, which leads to the release of interleukin 1β and interleukin 18, as well as several danger-associated molecular pattern molecules (DAMPs) that activate the mannan-binding lectin (MBL) pathway of the ComC, from cells of the innate immunity network. In support of this mechanism, we demonstrate that the Nlrp3 inflammasome become activated in innate immunity cells by granulocyte colony stimulating factor (G-CSF) and AMD3100 in an ATP-dependent manner. Moreover, administration of the Nlrp3 inflammasome activator nigericin induces mobilization in mice, and the opposite effect is obtained by administration of an Nlrp3 inhibitor (MCC950) to mice mobilized by G-CSF or AMD3100. In summary, our results further support the crucial role of innate immunity, BM sterile inflammation, and novel role of the ATP–Nlrp3–ComC axis in the egress of stem cells into PB. [ABSTRACT FROM AUTHOR]

Background: Acute myocardial infarction (AMI) and the ensuing ischemic heart disease are approaching an epidemic state. Limited stem cell retention following intracoronary administration has reduced the clinical efficacy of this novel therapy. Polymer based cell coating is biocompatible and has been shown to be safe. Here, we assessed the therapeutic utility of gelatin-based biodegradable cell coatings on bone marrow derived cell retention in ischemic heart. Methods: Gelatin based cell coatings were formed from the surface-mediated photopolymerization of 3% gelatin methacrylamide and 1% PEG diacrylate. Cell coating was confirmed using a multimodality approach including flow cytometry, imaging flow cytometry (ImageStream System) and immunohistochemistry. Biocompatibility of cell coating, metabolic activity of coated cells, and the effect of cell coating on the susceptibility of cells for engulfment were assessed using in vitro models. Following myocardial infarction and GFP+ BM-derived mesenchymal stem cell transplantation, flow cytometric and immunohistochemical assessment of retained cells was performed. Results: Coated cells are viable and metabolically active with coating degrading within 72 h in vitro. Importantly, cell coating does not predispose bone marrow cells to aggregation or increase their susceptibility to phagocytosis. In vitro and in vivo studies demonstrated no evidence of heightened immune response or increased phagocytosis of coated cells. Cell transplantation studies following myocardial infarction proved the improved retention of coated bone marrow cells compared to uncoated cells. Conclusion: Gelation based polymer cell coating is biologically safe and biodegradable. Therapies employing these strategies may represent an attractive target for improving outcomes of cardiac regenerative therapies in human studies. [ABSTRACT FROM AUTHOR]

Malignancy is a common cause of morbidity and mortality in the United States and around the world and the second leading cause of death in the United States. There is little data on the impact of metastatic cancer on the risk of hemorrhagic stroke or mortality among patients undergoing fibrinolytic therapy (FT) for acute PE. Using the National Inpatient Sample (NIS) database, we extracted admissions with a primary diagnosis of acute pulmonary embolism that underwent FT from 2010 to 2014. We performed a case control matched analysis between patients with and without metastatic cancer. Our primary outcome of interest was Mortality and our secondary outcome of interest was hemorrhagic stroke (HS). Of the 883,183 patients with a primary diagnosis of acute PE between 2010 and 12014, 23,690 patients (2.7%) underwent FT. After exclusion, 22,592 patients were included in the analysis. Of these, 941 patients (4.2%) were reported to have metastatic cancer. There was a higher incidence of cerebrovascular accidents and intubation/mechanical ventilation in the metastatic cancer arm. Mortality was significantly higher in the metastatic cancer arm with no difference in the incidence of HS. In multivariate regression analysis, among all patients that underwent FT for acute PE, metastatic cancer was associated with a significant odds for mortality (OR 1.91, 95% CI 1.11–5.82, p <.001). The presence of metastatic cancer in patients undergoing fibrinolytic therapy for acute pulmonary embolism is associated with increase mortality. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) can present with non-ST-segment elevation myocardial infarction (NSTEMI). The incidence, characteristics, outcomes, and treatment of this subgroup of patients with AF remains poorly studied. Using data from the National Inpatient Sample database, we (1) compared baseline characteristics of patients with AF with/without NSTEMI, (2) evaluated their outcomes and associated trends over the study period (2004-2013), and (3) evaluated revascularization (by percutaneous coronary intervention or coronary artery bypass graft [CABG]) and the impact on patient outcomes. Of the 3 923 436 patients admitted with a primary diagnosis of AF, 47 785 (1.2%) had a secondary diagnosis of NSTEMI. In this subgroup with AF and NSTEMI, there was a significant trend toward a decrease in mortality (P = .002), stroke (P < .001), and gastrointestinal bleeding (P < .001) during the study period. Compared to unrevascularized patients, revascularized patients were more likely to be younger (72.2 ± 10.2 vs 77.0 ± 11.8 years old, P < .001), male (57.8 vs 42.7%, P < .001), and had a much higher incidence of coronary risk factors. Revascularization was associated with increased survival in multivariable analysis (odds ratio: 0.562, 95% confidence interval: 0.334-0.946, P = .03). In conclusion, among patients admitted with AF, 1.2% were diagnosed with NSTEMI. A minority of patients with AF and NSTEMI underwent revascularization and had better in-hospital outcomes. [ABSTRACT FROM AUTHOR]

Takotsubo cardiomyopathy (TC) is definitively diagnosed following the exclusion of acute coronary syndrome. We aimed to examine the rate of coronary angiography in patients diagnosed with TC and also the outcome of patients with TC diagnosed with or without coronary angiography. We analyzed the National Inpatient Sample database from 2010 to 2014 and identified patients hospitalized with a primary diagnosis of TC. We compared in-hospital mortality between patients who underwent coronary angiography and those who did not. We also evaluated the association between coronary angiography and in-hospital mortality using a propensity score–adjusted multivariable analysis. Among 22 818 patients diagnosed with TC, 87.4% underwent coronary angiography and 12.6% did not. Patients who did not undergo coronary angiography had a higher in-hospital mortality than those who did (3.0% vs 0.9%; P < .001). Increased mortality in patients who did not undergo coronary angiogram was observed in both male (8.0% vs 2.8%; P = .03) and female patients (2.6% vs 0.7%; P < .001) and in patients 61 to 80 years old and ≥81 years old, but not in patients ≤60 years old. Multivariable analysis demonstrated that the lack of coronary angiography was independently associated with higher in-hospital mortality (adjusted odds ratio: 2.92; 95% confidence interval: 1.52-5.65; P = .001). [ABSTRACT FROM AUTHOR]