Prognostic Significance of Activated Monocytes in Patients with ST-Elevation Myocardial Infarction.

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.

Cangrelor in addition to standard therapy reduces cardiac damage and inflammatory markers in patients with ST-segment elevation myocardial infarction.

Although P2Y12 receptor blockers have become a standard, adjunctive therapy in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI), the optimal regimen has not been established. We performed a prospective, open-label, randomized study to investigate the effect of cangrelor administration on platelet function and inflammation in patients with primary PCI (PPCI). Twenty-two patients were randomized to receive either cangrelor and ticagrelor or ticagrelor alone (standard group) before PPCI. Platelet reactivity was evaluated at baseline (before PCI), 10 min and the end of the procedure. At baseline, there was no significant difference in platelet reactivity between both groups, whereas platelets were significantly inhibited at 10 min after initiating cangrelor vs. standard (adenosine-diphosphate-induced aggregation 102.2 ± 24.88 vs. 333.4 ± 63.3, P < 0.05 and thrombin-receptor-activating-peptide-induced aggregation 285.8 ± 86.1 vs. 624.8 ± 106.0, P < 0.05). Lower platelet aggregation in the cangrelor group persisted but the difference was reduced by the end of the procedure. Circulating inflammatory cells, pro-inflammatory cytokines, total elastase, and surrogates of neutrophil extracellular traps (total elastase-myeloperoxidase complexes) were significantly lower in the cangrelor compared to the standard therapy group at 6 h after randomization. There was a trend towards reduction in cardiac damage in the cangrelor group as reflected by the changes in late gadolinium enhancement between 48 h and 3 months after STEMI. Early administration of cangrelor in STEMI patients was associated with more effective platelet inhibition during PPCI and significantly dampened the deleterious inflammatory response compared to standard therapy (NCT03043274).

Comparative Effectiveness of Anti-Inflammatory Drug Treatments in Coronary Heart Disease Patients: A Systematic Review and Network Meta-Analysis.

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.

Autotaxin inhibition reduces cardiac inflammation and mitigates adverse cardiac remodeling after myocardial infarction.

OBJECTIVE: 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. APPROACH AND RESULTS: 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-Plpp3Δ) 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. CONCLUSION: 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.

A comparison of anticoagulation, antiplatelet, and placebo treatment for patients with heart failure reduced ejection fraction in sinus rhythm: a systematic review and meta-analysis.

Previous meta-analyses have not recommended routine warfarin use in heart failure (HF) patients but included limited data on contemporary anticoagulants and practices. We conducted an updated meta-analysis in light of newer literature evaluating rivaroxaban in this patient population. The aim of this meta-analysis was to assess if anticoagulation is associated with a decrease in all-cause mortality, myocardial infarction (MI), stroke, and hospitalization for HF exacerbation without an increased risk of major bleeding. A systematic search was conducted for randomized controlled trials to evaluate the use of antithrombotic therapy in patients with HF in sinus rhythm. Outcomes evaluated included all-cause mortality (ACM), non-fatal stroke, MI, hospitalization for HF exacerbation, and major bleeding. Five trials met criteria with a total of 9390 patients included. Four of the five trials evaluated warfarin use and one trial evaluated rivaroxaban. When anticoagulation was compared to control (antiplatelet and placebo groups), a significant reduction in ischemic stroke was found (OR 0.57; 95% CI, 0.42 to 0.78; P = 0.0005, I2 = 6.9%) and no significant difference was found in the risk of ACM, MI, or HF hospitalization. A significant increase in major bleeding was observed in the anticoagulation group when compared to the control group (OR 2.00; 95% CI, 1.45 to 2.75; P = < 0.0001, I2 = 25.79%). Anticoagulation in HF patients in normal sinus rhythm does not appear to reduce mortality rate, prevent MI, or decrease HF hospitalizations. Use reduces risk of ischemic stroke but is counterbalanced with an increase in major bleeding.

Comparison of intracoronary versus intravenous adenosine-induced maximal hyperemia for fractional flow reserve measurement: A systematic review and meta-analysis.

OBJECTIVE: We sought to perform a systematic review and meta-analysis of the available literature comparing fractional flow reserve (FFR) measurements after administration of adenosine using intracoronary (IC) bolus versus standard continuous intravenous (IV) infusion. BACKGROUND: FFR is considered the gold standard for invasive assessment of coronary lesions of intermediate severity. IV adenosine is recommended to induce hyperemia; however, IC adenosine is widely used for convenience. The difference between IV and IC administration in lesions assessment is not well studied. METHODS: We systematically searched MEDLINE and relevant databases for studies comparing IV with IC adenosine administration for FFR measurement. We reviewed data pertaining to adenosine doses, side effects, and FFR values. RESULTS: Eight studies addressing the primary question were identified. Dose of IC adenosine varied between 36 and 600 µg. Compared to IV adenosine infusion, the sensitivity of IC administration is 0.805 (95% confidence interval [95% CI]: 0.664-0.896; p < .001), specificity is 0.965 (95% CI: 0.932-0.983; p < .001), positive likelihood ratio is 24.218 (95% CI: 12,263-47.830; p < .001), negative likelihood ratio is 0.117 (95% CI: 0.033-0.411; p < .01), and diagnostic odds ratio is 274.225 [95% CI: 92.731-810.946; p < .001]. Overall, hemodynamic side effects and symptoms were reported more frequently with IV adenosine. CONCLUSIONS: The available literature suggests that IC adenosine is well tolerated and may provide equivalent diagnostic accuracy compared to IV administration. However, variability in dosing regimens does not allow definitive conclusions regarding noninferiority of IC approach compared to IV administration.

Prognostic Role of Elevated Myeloperoxidase in Patients with Acute Coronary Syndrome: A Systemic Review and Meta-Analysis.

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.

Regional end-systolic circumferential strain demonstrates compensatory segmental contractile function in patients with ST-segment elevation myocardial infarction.

Myocardial strain has shown tremendous promise as a potential diagnostic tool for characterizing ventricular function. With regards to myocardial infarction, global circumferential strain (CS) can be used to assess overall function, while regional CS can identify local alterations in contractility. Currently, there is a lack of data related to regional strain in patients with ST-segment elevation myocardial infarction (STEMI). Thus, the goal of this study was to quantify regional strain patterns in STEMI and normal control patients, measuring both peak CS and end-systolic (ES) CS in the mid-ventricular region. This was done by conducting cardiac magnetic resonance (CMR) imaging acutely after STEMI patients underwent primary percutaneous coronary intervention. The CMR datasets were then analyzed using feature-tracking of the cine images. The patients were broken into three groups: (1) control patients (N = 18), (2) STEMI patients with ejection fraction (EF) ≥ 50% (N = 20), and (3) STEMI patients with EF < 50% (N = 20). The key result of the analysis was that ES CS detected a significant increase in the magnitude of strain in the non-infarcted tissue of STEMI patients with EF ≥ 50% when compared to STEMI patients with EF < 50%, whereas peak CS did not detect any differences. This implies that the tissue in this region is contracting more strongly compared to non-infarcted tissue in STEMI patients with EF < 50%. Thus, regional ES CS could potentially be utilized as a diagnostic tool for assessing STEMI patients, by detecting regional changes in contractility after PCI, which could assist in treatment planning.

Structural and Electrochemical Analysis of CIGS: Cr Crystalline Nanopowders and Thin Films Deposited onto ITO Substrates.

A new approach for the synthesis of nanopowders and thin films of CuInGaSe2 (CIGS) chalcopyrite material doped with different amounts of Cr is presented. The chalcopyrite material CuInxGa1 - xSe2 was doped using Cr to form a new doped chalcopyrite with the structure CuInxCryGa1 - x - ySe2, where x = 0.4 and y = 0.0, 0.1, 0.2, or 0.3. The electrical properties of CuInx CryGa1 - x - ySe2 are highly dependent on the Cr content and results show these materials as promising dopants for the fabrication thin film solar cells. The CIGS nano-precursor powder was initially synthesized via an autoclave method, and then converted into thin films over transparent substrates. Both crystalline precursor powders and thin films deposited onto ITO substrates following a spin-coating process were subsequently characterized using XRD, SEM, HR-TEM, UV-visible and electrochemical impedance spectroscopy (EIS). EIS measurement was performed to evaluate the dc-conductivity of these novel materials as conductive films to be applied in solar cells.

Identification of Human Very Small Embryonic like Stem Cells (VSELS) in Human Heart Tissue Among Young and Old Individuals.

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.

Highly Selective Optical Sensor Eu (TTA)3 Phen Embedded in Poly Methylmethacrylate for Assessment of Total Prostate Specific Antigen Tumor Marker in Male Serum Suffering Prostate Diseases.

A low-cost, simple, and highly selective method was used for the assessment of total prostate specific antigen (tPSA) in the serum of prostate cancer patients. This method is based on quenching the intensity of luminescence displayed by the optical sensor Eu (TTA)3 phen/poly methylmethacrylate (PMMA) thin membrane or film upon adding different concentrations of tPSA. The luminescent optical sensor was synthesized and characterized through absorption, emission, scanning electron microscopy (SEM), and x-ray diffraction (XRD), and is tailored to present red luminescence at 614 nm upon excitation at 395 nm in water. The fabricated sensor fluorescence intensity is quenched in the presence of tPSA in aqueous media. The fluorescence resonance energy transfer (FRET) is the main mechanism by which the sensor performs. The sensor was successfully utilized to estimate tPSA in the serum of patients suffering prostate cancer in a time and cost effective way. The statistical results of the method were satisfactory with 0.0469 ng mL-1 as a detection limit and 0.99 as a correlation coefficient.

Characterization and radiological impacts assessment of scale TENORM waste produced from oil and natural gas production in Egypt.

This study aims to identify the analytical and radiological characterization of scale TENORM waste produced from oil and natural gas productions in the western desert in Egypt and evaluates their radiological impacts. The mean activity concentration of 238U, 226Ra, 210Pb, 228Ra, 224Ra, and 40K measured in scale TENORM samples is 660 ± 63, 1979 ± 435, 1399 ± 211, 645 ± 104, 794 ± 116, and 556 ± 86 Bq/kg, respectively. Radiological hazard parameters (Raeq, Hex, Hin, etc.) were estimated form the scale TENORM waste sample. All the calculated hazard parameters were found greater than the permissible and recommended safe levels. So the exposure to radiations released from the accumulation of the petroleum scale TENORM waste may cause health risks to the operators and who inhale radioactive radon gases and/or ingest contaminants by radiotoxic nuclides of U, Th, Ra, and Pb. Also, the risks may be extended to the near and/or the general environment.

Percutaneous Coronary Intervention With Drug-Eluting Stent Versus Optimal Medical Therapy for Chronic Total Occlusion: Systematic Review and Meta-Analysis.

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.

Efficacy and safety of short-term dual antiplatelet therapy (≤6 months) after percutaneous coronary intervention for acute coronary syndrome: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Patients who undergo percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are at increased risk for subsequent ischemic events. HYPOTHESIS: Short-term dual antiplatelet therapy (DAPT) (≤6 months) is inferior to standard or long-term DAPT in patients who undergo PCI for ACS events. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials that compared short-term (≤6 months) to long-term (≥12 months) DAPT after PCI for ACS. We searched MEDLINE, EMBASE, SCOPUS, and the Cochrane Central Register of Controlled Trials database. RESULTS: Ten randomized controlled trials, including a total of 12 696 patients, met our inclusion criteria. For short-term DAPT, duration of therapy ranged from 3 to 6 months, while long-term DAPT ranged from 12 to 24 months. The majority of studies used clopidogrel and second-generation drug-eluting stents. No statistically significant difference was found between short-term and long-term DAPT with regard to myocardial infarction (odds ratio 1.21; 95% confidence interval 0.94-1.57; P = 0.14), stent thrombosis (odds ratio 1.54; 95% confidence interval 1.00-2.38; P = 0.052), or major bleeding events (odds ratio 0.74; 95% confidence interval 0.49-1.11; P = 0.14). There was no significant difference in all-cause mortality, cardiac death, or net adverse cardiac and cerebrovascular events. CONCLUSIONS: Our meta-analysis demonstrated that short-term DAPT (<6 months) after PCI for ACS was not associated with increased risk of myocardial infarction or stent thrombosis when compared to long-term DAPT.

Determination of Diquat Residues in Potato Using Reversed-Phase Liquid Chromatography with Tandem Mass Spectrometry.

A simple, modified quick, easy, cheap, effective, rugged, and safe procedure was developed for the determination of diquat in potato using reversed-phase LC coupled with tandem MS (MS/MS) in a total run time of 10 min. Different sample preparation parameters (pH modifier type, sample size, and elevated temperature) were tested and optimized. Potato sample was extracted with acetonitrile in the presence of ammonium hydroxide at 80°C. Phase separation was obtained by shaking the extract with magnesium sulfate and sodium chloride, and analysis was done using LC-MS/MS. Matrix-matched standard calculations were used to compensate for matrix-induced suppression in LC-MS/MS determination. The precision and trueness of the method were determined from recovery experiments on five replicates of spiked blank potato samples at 0.01, 0.05, and 0.1 mg/kg. The range of the obtained recoveries was 74-110%, with RSD values <5% for all the concentrations.

Screening the bio-safety of wheat produced from pretreated grains to enhance tolerance against drought using physiological and spectroscopic methods.

Drought is a serious abiotic stress, causes worldwide intensive reduction in crop growth and productivity. Plants in contrast to other organisms, do not enjoy the luxury of being able to change their environment or seeking shelters. In this investigation, wheat grains were pre-soaked for 12h in salicylic acid (SA) and/or thiourea (ThU) prior they were left to grow in dry land (40% field water capacity) until harvest. The bio-safety of the harvested wheat was deduced using technical physiological and spectral methods. The pretreatment using SA up to ( approximately 1.5mmol) viewed homologous protein profile and less flag leaf proline in comparison to the non-stressed wheat. In addition, SA-pretreatment has maintained 70% of the emission intensity of yielded grain. The spectra of FTIR were more or less similar in yielded grain and flag leaf in SA-pretreatment. On the other hand, ThU pretreatment induced varied protein profile, higher proline than normal, reduced the fluorescence emission intensity by 52%, and induced varied FTIR spectra. Pretreatment of SA not only has enhanced wheat productivity but also increased yield and straw productions even above the non-treated-non-stressed wheat plant. In contrast to ThU SA was considered safe for drought-stress alleviation in crop plant agriculture.