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Abstract Global ischemia has been shown to induce cardiac regenerative response in animal models. One of the suggested mechanisms behind cardiac regeneration is dedifferentiation of cardiomyocytes. How human adult cardiomyocytes respond to global ischemia is not fully known. In this study, biopsies from the left ventricle (LV) and the atrioventricular junction (AVj), a potential stem cell niche, were collected from multi-organ donors with cardiac arrest (N = 15) or without cardiac arrest (N = 6). Using immunohistochemistry, we investigated the expression of biomarkers associated with stem cells during cardiomyogenesis; MDR1, SSEA4, NKX2.5, and WT1, proliferation markers PCNA and Ki67, and hypoxia responsive factor HIF1α. The myocyte nuclei marker PCM1 and cardiac Troponin T were also included. We found expression of cardiac stem cell markers in a subpopulation of LV cardiomyocytes in the cardiac arrest group. The same cells showed a low expression of Troponin T indicating remodeling of cardiomyocytes. No such expression was found in cardiomyocytes from the control group. Stem cell biomarker expression in AVj was more pronounced in the cardiac arrest group. Furthermore, co-expression of PCNA and Ki67 with PCM1 was only found in the cardiac arrest group in the AVj. Our results indicate that a subpopulation of human cardiomyocytes in the LV undergo partial dedifferentiation upon global ischemia and may be involved in the cardiac regenerative response together with immature cardiomyocytes in the AVj.

Objective: Tricuspid annuloplasty is associated with increased risk of atrioventricular block and subsequent implantation of a permanent pacemaker. However, the exact incidence of permanent pacemaker, associated risk factors, and outcomes in this frame remain debated. The aim of the study was to report permanent pacemaker incidence, risk factors, and outcomes after tricuspid annuloplasty from nationwide databases. Methods: By using data from multiple Swedish mandatory national registries, all patients (n = 1502) who underwent tricuspid annuloplasty in Sweden from 2006 to 2020 were identified. Patients who needed permanent pacemaker within 30 days from surgery were compared with those who did not. The cumulative incidence of permanent pacemaker implantation was estimated. A multivariable logistic regression model was fit to identify risk factors of 30-day permanent pacemaker implantation. The association between permanent pacemaker implantation and long-term survival was evaluated with multivariable Cox regression. Results: The 30-day permanent pacemaker rate was 14.2% (214/1502). Patients with permanent pacemakers were older (69.8 ± 10.3 years vs 67.5 ± 12.4 years, P = .012). Independent risk factors of permanent pacemaker implantation were concomitant mitral valve surgery (odds ratio, 2.07; 95% CI, 1.34-3.27), ablation surgery (odds ratio, 1.59; 95% CI, 1.12-2.23), and surgery performed in a low-volume center (odds ratio, 1.85; 95% CI, 1.17-2.83). Permanent pacemaker implantation was not associated with increased long-term mortality risk (adjusted hazard ratio, 0.74; 95% CI, 0.53-1.03). Conclusions: This nationwide study demonstrated a high risk of permanent pacemaker implantation within 30 days of tricuspid annuloplasty. However, patients who needed a permanent pacemaker did not have worse long-term survival, and the cumulative incidence of heart failure and major adverse cardiovascular events was similar to patients who did not receive a permanent pacemaker.

Background: There is scarce knowledge about the association between socioeconomic status and mortality in patients undergoing surgical aortic valve replacement. This study explores the associations between income, education and marital status, and long-term mortality risk. Methods: In this national registry-based observational cohort study we included all 14,537 patients aged >18 years who underwent isolated surgical aortic valve replacement for aortic stenosis in Sweden 1997–2020. Socioeconomic status and comorbidities were collected from three mandatory national registries. Cox regression models adjusted for patient characteristics and comorbidities were used to estimate the mortality risk. Results: Mortality risk was higher for patients in the lowest versus the highest income quintile (adjusted hazard ratio [aHR] 1.36, 95 % confidence interval [CI]: 1.11–1.65), for patients with 12 years (aHR 1.20, 95 % CI:1.08–1.33), and for patients who were not married/cohabiting versus those who were (aHR 1.24, 95 % CI:1.04–1.48). Patients with the most unfavorable socioeconomic status (lowest income, shortest education, never married/cohabiting) had an adjusted median survival of 2.9 years less than patients with the most favorable socioeconomic status (14.6 years, 95 % CI: 13.2–17.4 years vs. 11.7 years, 95 % CI: 9.8–14.4). Conclusions: Low socioeconomic status in patients undergoing surgical aortic valve replacement is associated with shorter survival and an increased long-term adjusted mortality risk. These results emphasize the importance of identifying surgical aortic valve replacement patients with unfavorable socioeconomic situation and ensure sufficient post-discharge surveillance.

Abstract Cardiovascular disease (CVD) is strongly associated with chronic low-grade inflammation, involving activated Toll-like receptors and their downstream cellular machinery. Moreover, CVD and other related inflammatory conditions are associated with infiltration of bacteria and viruses originating from distant body sites. Thus, in this study we aimed to map the presence of microbes in the myocardium of patients with heart disease that we previously found to display upregulated Toll-like receptor signaling. We performed metagenomics analysis of atrial cardiac tissue from patients undergoing coronary artery bypass grafting (CABG) or aortic valve replacement (AVR) and compared with atrial cardiac tissue from organ donors. A total of 119 species of bacteria and seven species of virus were detected in the cardiac tissue. RNA expression of five bacterial species were increased in the patient group of which L. kefiranofaciens correlated positively with cardiac Toll-like receptor-associated inflammation. Interaction network analysis revealed four main gene set clusters involving cell growth and proliferation, Notch signaling, G protein signaling and cell communication in association with L. kefiranofaciens RNA expression. Taken together, intracardial expression of L. kefiranofaciens RNA correlates with pro-inflammatory markers in the diseased cardiac atrium and may have an effect on specific signaling processes important for cell growth, proliferation and cell communication.

Abstract Previous studies have demonstrated that environmental and temporal factors may affect the incidence of acute type A aortic dissection (ATAAD). Here, we aimed to investigate the hypothesis that national holidays and weekends influence the incidence of surgery for ATAAD. For the period 1st of January 2005 until 31st of December 2019, we investigated a hypothesised effect of (country-specific) national holidays and weekends on the frequency of 2995 surgical repairs for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Compared to other days, the number of ATAAD repairs were 29% (RR 0.71; 95% CI 0.54–0.94) lower on national holidays and 26% (RR 0.74; 95% CI 0.68–0.82) lower on weekends. As day of week patterns of symptom duration were assessed and the primary analyses were adjusted for period of year, our findings suggest that the reduced surgical incidence on national holidays and weekends does not seem to correspond to seasonal effects or surgery being delayed and performed on regular working days.

In this post hoc study, arachidonic acid (AA)-induced platelet aggregation during pregnancy with and without acetylsalicylic acid (ASA) treatment was studied in 323 women with unexplained recurrent first-trimester miscarriage and in 59 healthy women with normal pregnancies. All women had normal AA-induced platelet aggregation in the non-pregnant state. Women with recurrent miscarriage were treated with 75 mg ASA or placebo daily. AA-induced platelet aggregation was measured with multiple electrode impedance aggregometry and presented in units (U), where 1 U = 10 aggregation units x minutes. There were no significant differences in platelet aggregation between placebo-treated women with recurrent miscarriage and healthy women. The mean differences were -0.7 (95%CI; −7.0; 5.6) U in the non-pregnant state, 3.8 (95%CI; −4.6; 12.2) U during the late first trimester and 1.7 (95%CI; −6.7; 10.3) U and 4.1 (95%CI; −3.9; 12.0) U during the early and late third trimester, respectively. ASA reduced platelet aggregation by median −84.0% (Q1; Q3; −89.8; −76.3), −79.9% (−84.7; −69.2) and −75.7% (−83.5; −49.5), respectively, during pregnancy. The degree of inhibition by ASA decreased during the third trimester (p

We aimed to investigate a hypothesised association between daily mean temperature and the risk of surgery for acute type A aortic dissection (ATAAD). For the period of 1 January 2005 until 31 December 2019, we collected daily data on mean temperatures and date of 2995 operations for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Using a two-stage time-series approach, we investigated the association between hot and cold temperatures relative to the optimal temperature and the rate of ATAAD repair in the selected cities. The relative risks (RRs) of cold temperatures (≤−5°C) and hot temperatures (≥21°C) compared to optimal temperature were 1.47 (95% CI: 0.72–2.99) and 1.43 (95% CI: 0.67–3.08), respectively. In line with previous studies, we observed increased risk at cold and hot temperatures. However, the observed associations were not statistically significant, thus only providing weak evidence of an association.

Background The CHA2DS2‐VASc (congestive heart failure, hypertension, age ≥75 years, diabetes, previous stroke or TIA [transient ischemic attack], vascular disease, age 65 to 74 years, sex category female; 2 indicates 2 points, otherwise 1 point) scoring system is recommended to guide decisions on oral anticoagulation therapy for stroke prevention in patients with nonsurgery atrial fibrillation. A score ≥1 in men and ≥2 in women, corresponding to an annual stroke risk exceeding 1%, warrants long‐term oral anticoagulation provided the bleeding risk is acceptable. However, in patients with new‐onset postoperative atrial fibrillation, the optimal risk stratification method is unknown. The aim of this study was therefore to evaluate the CHA2DS2‐VASc scoring system for estimating the 1‐year ischemic stroke risk in patients with new‐onset postoperative atrial fibrillation after coronary artery bypass grafting. Methods and Results All patients with new‐onset postoperative atrial fibrillation and without oral anticoagulation after first‐time isolated coronary artery bypass grafting performed in Sweden during 2007 to 2017 were eligible for this registry‐based observational cohort study. The 1‐year ischemic stroke rate at each step of the CHA2DS2‐VASc score was estimated using a Kaplan‐Meier estimator. Of the 6368 patients included (mean age, 69.9 years; 81% men), >97% were treated with antiplatelet drugs. There were 147 ischemic strokes during the first year of follow‐up. The ischemic stroke rate at 1 year was 0.3%, 0.7%, and 1.5% in patients with CHA2DS2‐VASc scores of 1, 2, and 3, respectively, and ≥2.3% in patients with a score ≥4. A sensitivity analysis, with the inclusion of patients on anticoagulants, was performed and supported the primary results. Conclusions Patients with new‐onset atrial fibrillation after coronary artery bypass grafting and a CHA2DS2‐VASc score

Therapeutic angiogenesis may improve outcomes in patients with coronary artery disease undergoing surgical revascularization. Angiogenic factors may promote blood vessel growth and regenerate regions of ischemic but viable myocardium. Previous clinical trials of vascular endothelial growth factor A (VEGF-A) gene therapy with DNA or viral vectors demonstrated safety but not efficacy. AZD8601 is VEGF-A165 mRNA formulated in biocompatible citrate-buffered saline and optimized for high-efficiency VEGF-A expression with minimal innate immune response. EPICCURE is an ongoing randomized, double-blind, placebo-controlled study of the safety of AZD8601 in patients with moderately decreased left ventricular function (ejection fraction 30%–50%) undergoing elective coronary artery bypass surgery. AZD8601 3 mg, 30 mg, or placebo is administered as 30 epicardial injections in a 10-min extension of cardioplegia. Injections are targeted to ischemic but viable myocardial regions in each patient using quantitative 15O-water positron emission tomography (PET) imaging (stress myocardial blood flow < 2.3 mL/g/min; resting myocardial blood flow > 0.6 mL/g/min). Improvement in regional and global myocardial blood flow quantified with 15O-water PET is an exploratory efficacy outcome, together with echocardiographic, clinical, functional, and biomarker measures. EPICCURE combines high-efficiency delivery with quantitative targeting and follow-up for robust assessment of the safety and exploratory efficacy of VEGF-A mRNA angiogenesis (ClinicalTrials.gov: NCT03370887).

Cardiomyocyte proliferation has emerged as the main source of new cardiomyocytes in the adult. Progenitor cell populations may on the other hand contribute to the renewal of other cell types, including endothelial and smooth muscle cells. The phenotypes of immature cell populations in the adult human heart have not been extensively explored. We therefore investigated whether SSEA4+CD34- cells might constitute immature cycling cardiomyocytes in the adult failing and non-failing human heart. The phenotypes of Side Population (SP) and C-kit+CD45- progenitor cells were also analyzed. Biopsies from the four heart chambers were obtained from patients with end-stage heart failure as well as organ donors without chronic heart failure. Freshly dissociated cells underwent flow cytometric analysis and sorting. SSEA4+CD34- cells expressed high levels of cardiomyocyte, stem cell and proliferation markers. This pattern resembles that of cycling, immature, cardiomyocytes, which may be important in endogenous cardiac regeneration. SSEA4+CD34- cells isolated from failing hearts tended to express lower levels of cardiomyocyte markers as well as higher levels of stem cell markers. C-kit+CD45- and SP CD45- cells expressed high levels of endothelial and stem cell markers-corresponding to endothelial progenitor cells involved in endothelial renewal.

Abstract Background Single centre studies support No Touch (NT) saphenous vein graft (SVG) harvesting technique. The primary objective of the SUPERIOR SVG study was to determine whether NT versus conventional (CON) SVG harvesting was associated with improved SVG patency 1 year after coronary artery bypass grafting surgery (CABG). Methods Adults undergoing isolated CABG with at least 1 SVG were eligible. CT angiography was performed 1-year post CABG. Leg adverse events were assessed with a questionnaire. A systematic review was performed for published NT graft patency studies and results aggregated including the SUPERIOR study results. Results Two hundred and-fifty patients were randomized across 12-centres (NT 127 versus CON 123 patients). The primary outcome (study SVG occlusion or cardiovascular (CV) death) was not significantly different in NT versus CON (NT: 7/127 (5.5%), CON 13/123 (10.6%), p = 0.15). Similarly, the proportion of study SVGs with significant stenosis or total occlusion was not significantly different between groups (NT: 8/102 (7.8%), CON: 16/107 (15.0%), p = 0.11). Vein harvest site infection was more common in the NT patients 1 month postoperatively (23.3% vs 9.5%, p

Background The long‐term impact of new‐onset postoperative atrial fibrillation (POAF) after coronary artery bypass grafting and the benefit of early‐initiated oral anticoagulation (OAC) in patients with POAF are uncertain. Methods and Results All patients who underwent coronary artery bypass grafting without preoperative atrial fibrillation in Sweden from 2007 to 2015 were included in a population‐based study using data from 4 national registries: SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence‐based Care in Heart Disease Evaluated According to Recommended Therapies), National Patient Registry, Dispensed Drug Registry, and Cause of Death Registry. POAF was defined as any new‐onset atrial fibrillation during the first 30 postoperative days. Cox regression models (adjusted for age, sex, comorbidity, and medication) were used to assess long‐term outcome in patients with and without POAF, and potential associations between early‐initiated OAC and outcome. In a cohort of 24 523 patients with coronary artery bypass grafting, POAF occurred in 7368 patients (30.0%), and 1770 (24.0%) of them were prescribed OAC within 30 days after surgery. During follow‐up (median 4.5 years, range 0‒9 years), POAF was associated with increased risk of ischemic stroke (adjusted hazard ratio [aHR] 1.18 [95% CI, 1.05‒1.32]), any thromboembolism (ischemic stroke, transient ischemic attack, or peripheral arterial embolism) (aHR 1.16, 1.05‒1.28), heart failure hospitalization (aHR 1.35, 1.21‒1.51), and recurrent atrial fibrillation (aHR 4.16, 3.76‒4.60), but not with all‐cause mortality (aHR 1.08, 0.98‒1.18). Early initiation of OAC was not associated with reduced risk of ischemic stroke or any thromboembolism but with increased risk for major bleeding (aHR 1.40, 1.08‒1.82). Conclusions POAF after coronary artery bypass grafting is associated with negative prognostic impact. The role of early OAC therapy remains unclear. Studies aiming at reducing the occurrence of POAF and its consequences are warranted.

Cardiac hypertrophy is a condition that may contribute to the development of heart failure. In this study, we compare the gene-expression patterns of our in vitro stem-cell-based cardiac hypertrophy model with the gene expression of biopsies collected from hypertrophic human hearts. Twenty-five differentially expressed genes (DEGs) from both groups were identified and the expression of selected corresponding secreted proteins were validated using ELISA and Western blot. Several biomarkers, including CCN2, THBS1, NPPA, and NPPB, were identified, which showed significant overexpressions in the hypertrophic samples in both the cardiac biopsies and in the endothelin-1-treated cells, both at gene and protein levels. The protein-interaction network analysis revealed CCN2 as a central node among the 25 overlapping DEGs, suggesting that this gene might play an important role in the development of cardiac hypertrophy. GO-enrichment analysis of the 25 DEGs revealed many biological processes associated with cardiac function and the development of cardiac hypertrophy. In conclusion, we identified important similarities between ET-1-stimulated human-stem-cell-derived cardiomyocytes and human hypertrophic cardiac tissue. Novel putative cardiac hypertrophy biomarkers were identified and validated on the protein level, lending support for further investigations to assess their potential for future clinical applications.

Cardiac hypertrophy is an important and independent risk factor for the development of heart failure. To better understand the mechanisms and regulatory pathways involved in cardiac hypertrophy, there is a need for improved in vitro models. In this study, we investigated how hypertrophic stimulation affected human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs). The cells were stimulated with endothelin-1 (ET-1) for 8, 24, 48, 72, or 96 h. Parameters including cell size, ANP-, proBNP-, and lactate concentration were analyzed. Moreover, transcriptional profiling using RNA-sequencing was performed to identify differentially expressed genes following ET-1 stimulation. The results show that the CMs increase in size by approximately 13% when exposed to ET-1 in parallel to increases in ANP and proBNP protein and mRNA levels. Furthermore, the lactate concentration in the media was increased indicating that the CMs consume more glucose, a hallmark of cardiac hypertrophy. Using RNA-seq, a hypertrophic gene expression pattern was also observed in the stimulated CMs. Taken together, these results show that hiPSC-derived CMs stimulated with ET-1 display a hypertrophic response. The results from this study also provide new molecular insights about the underlying mechanisms of cardiac hypertrophy and may help accelerate the development of new drugs against this condition.

Background Low income and short education have been found to be independently associated with inferior survival after coronary artery bypass grafting (CABG), whereas the use of secondary prevention medications is associated with improved survival. We investigated whether underusage of secondary prevention medications contributes to the inferior long‐term survival in CABG patients with a low income and short education. Methods and Results Patients who underwent CABG in Sweden between 2006 to 2015 and survived at least 6 months after discharge (n=28 448) were included in a population‐based cohort study. Individual patient data from 5 national registries, including the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies) registry, covering dispensing of secondary prevention medications (statins, platelet inhibitors, β‐blockers, and RAAS inhibitors), socioeconomic factors, patient characteristics, comorbidity, and long‐term mortaity were merged. All‐cause mortality risk was estimated using multivariable Cox regression models adjusted for patient characteristics, baseline comorbidities, time‐updated secondary prevention medications, and socioeconomic status. Long‐term mortality was higher in patients with a low income and short education. Statins and platelet inhibitors were dispensed less often to patients with a low income, both at baseline and after 8 years. The decline in dispensing over time was steeper for low‐income patients. Short education was not associated with reduced dispensing of any secondary prevention medication. Use of statins (adjusted hazard ratio=0.57 [95% CI, 0.53–0.61]), RAAS inhibitors (adjusted hazard ratio=0.78 [0.73–0.84]), and platelet inhibitors (adjusted hazard ratio=0.74 [0.68–0.80]) were associated with reduced long‐term mortality irrespective of socioeconomic status. Conclusions Secondary prevention medications are dispensed less often after CABG to patients with low income. Underusage of secondary prevention medications after CABG is associated with increased mortality risk independently of income and extent of education.

Cardiac hypertrophy is an important and independent risk factor for the development of cardiac myopathy that may lead to heart failure. The mechanisms underlying the development of cardiac hypertrophy are yet not well understood. To increase the knowledge about mechanisms and regulatory pathways involved in the progression of cardiac hypertrophy, we have developed a human induced pluripotent stem cell (hiPSC)-based in vitro model of cardiac hypertrophy and performed extensive characterization using a multi-omics approach. In a series of experiments, hiPSC-derived cardiomyocytes were stimulated with Endothelin-1 for 8, 24, 48, and 72 h, and their transcriptome and secreted proteome were analyzed. The transcriptomic data show many enriched canonical pathways related to cardiac hypertrophy already at the earliest time point, e.g., cardiac hypertrophy signaling. An integrated transcriptome–secretome analysis enabled the identification of multimodal biomarkers that may prove highly relevant for monitoring early cardiac hypertrophy progression. Taken together, the results from this study demonstrate that our in vitro model displays a hypertrophic response on both transcriptomic- and secreted-proteomic levels. The results also shed novel insights into the underlying mechanisms of cardiac hypertrophy, and novel putative early cardiac hypertrophy biomarkers have been identified that warrant further investigation to assess their potential clinical relevance.

Background Little is known of the impact of social factors on mortality after coronary artery bypass grafting (CABG). We explored sex‐ and age‐specific associations between mortality risk after CABG and marital status, income, and education. Methods and Results This population‐based register study included 110 742 CABG patients (21.3% women) from the SWEDEHEART registry (Swedish Web‐system for Enhancement and Development of Evidence‐based Care in Heart Disease Evaluated According to Recommended Therapies) operated 1992 to 2015. Cox regression models were used to study the relation between social factors and all‐cause mortality. Never having been married compared with being married/cohabiting was associated with a higher risk in women than in men (hazard ratio 1.32, 95% CI 1.20–1.44) versus 1.17 (1.13–1.22), P=0.030 between sex. The lowest income quintile, compared with the highest, was associated with higher risk in men than in women (hazard ratio 1.44 [1.38–1.51] versus 1.25 [1.14–1.38], P=0.0036). Lowest education level was associated with higher risk without sex difference (hazard ratio 1.15 [1.11–1.19] versus 1.25 [1.16–1.35], P=0.75). For unmarried women aged 60 years at surgery with low income and low education, mortality 10 years after surgery was 18%, compared with 11% in married women with high income and higher education level. The median life expectancy was 4.8 years shorter. Corresponding figures for 60‐year‐old men were 21% versus 12% mortality risk at 10 years and 5.0 years shorter life expectancy. Conclusions There are strong associations between social factors and mortality risk after CABG in both men and women. These results emphasize the importance of developing and implementing secondary prevention strategies for CABG patients with disadvantages in social factors.

Despite the fact that the origin of human immunodeficiency virus (HIV) being a contamination and a mutation originating from primates is well-documented alternative narratives are often being heard ofespecially in sub-Saharan Africa. One such narrative is about HIV being man-made in a military laboratory in the United States. In this article, it is shown how this narrative was fabricated by the intelligence services in East Germany (German Democratic Republic – GDR) as part of the ideological warfare during the Cold War. The purpose of this article is to put an end to a long-lasting conspiracy theory, which is still alive and may create diversion from serious research on the topic.

BackgroundAdenosine‐assisted transthoracic Doppler‐derived coronary flow reserve (TDE‐CFR) reflects coronary vascular function. The prognostic and incremental value of left anterior descending coronary artery TDE‐CFR above myocardial perfusion scintigraphy in patients with suspected myocardial ischemia has not yet been studied. Methods and ResultsThree hundred seventy‐one patients (mean age, 62.3±8.7 years; 46.8% males) referred to myocardial perfusion scintigraphy attributed to suspected myocardial ischemia were included in the study. The TDE‐CFR result was blinded to the referring physician. Patients were followed up regarding major cardiovascular events, defined as cardiovascular death, myocardial infarction, or acute revascularization during a median follow‐up time of 4.5 years. A TDE‐CFR value of ≤2.0 was considered reduced. Major cardiovascular events occurred during follow‐up in 60 patients (16.2%). A reduced TDE‐CFR was detected in 76 patients (20.5%). Patients with reduced TDE‐CFR had an event rate of 36.8% compared to 10.8% in patients with normal TDE‐CFR (unadjusted hazard ratio, 4.63; 95% CI, 2.78–7.69; P

Vascular diseases are increasing health problems affecting >25 million individuals in westernized societies. Such patients could benefit from transplantation of tissue-engineered vascular grafts using autologous cells. One challenge that has limited this development is the need for cell isolation, and risks associated with ex vivo expanded stem cells. Here we demonstrate a novel approach to generate transplantable vascular grafts using decellularized allogeneic vascular scaffolds, repopulated with peripheral whole blood (PWB) in vitro in a bioreactor. Circulating, VEGFR-2+/CD45+ and a smaller fraction of VEGFR-2+/CD14+ cells contributed to repopulation of the graft. SEM micrographs showed flat cells on the luminal surface of the grafts consistent with endothelial cells. For clinical validation, two autologous PWB tissue-engineered vein conduits were prepared and successfully used for by-pass procedures in two pediatric patients. These results provide a proof of principle for the generation of transplantable vascular grafts using a simple autologous blood sample, making it clinically feasible globally.

Purpose: Embolic stroke is a dreaded complication of thoracic endovascular aortic repair. The prevailing theory about its cause is that particulate debris from atherosclerotic lesions in the aortic wall are dislodged by endovascular instruments and embolize to the brain. An alternative source of embolism might be air trapped in the endograft delivery system. The aim of this experimental study was to determine whether air is released during deployment of a thoracic endograft. Methods: In an experimental benchtop study, eight thoracic endografts (five Medtronic Valiant Thoracic and three Gore TAG) were deployed in a water-filled transparent container drained from air. Endografts were prepared and deployed according to their instructions for use. Deployment was filmed and the volume of air released was collected and measured in a calibrated syringe. Results: Air was released from all the endografts examined. Air volumes ranged from 0.1 to 0.3 mL for Medtronic Valiant Thoracic and from

Ischemic heart disease is a major cause of death and morbidity and the search for novel therapeutic targets is still required. We have previously shown that the enzyme arachidonate 15 lipoxygenase (ALOX15), which catalyzes the conversion of arachidonic acid to 15-hydroxy eicosatetraenoic acid (15-HETE), is highly expressed in ischemic heart tissue, but its role in the pathogenesis of ischemic heart disease is unclear. Here we showed that expression of ALOX15, but not ALOX12 or ALOX15B, was increased in ischemic versus non-ischemic human heart biopsy samples. A similar ALOX expression pattern was found in hypoxic human cardiomyocytes and cardiac endothelial cells. We also showed that levels of 15-HETE were significantly higher in ischemic versus non-ischemic human heart biopsy samples and showed a tendency to increase in serum from the patients with ischemic heart disease. Moreover, hypoxia increased the production of 15-HETE levels from human cardiomyocytes and cardiac endothelial cells. The hypoxia-induced increase in 15-HETE levels from human cardiomyocytes was inhibited by the ALOX15 inhibitor baicalein. Finally, by using intrinsic rotational thromboelastometry, we showed that human whole blood clotted faster in the presence of 15-HETE. In summary, we propose that increased ALOX15 expression in heart tissue under ischemic conditions may lead to increased production of 15-HETE, potentially contributing to thrombosis.

Bleeding complications are common in cardiac surgery. Perioperative handling of heparin and protamine may influence the haemostasis. We hypothesized that heparin and protamine dosing based on individual titration curves would improve haemostasis in comparison to standard dosing.Sixty patients scheduled for first time elective coronary artery bypass grafting or valve surgery were included in a prospective randomized study. The patients were randomized to heparin and protamine dosing with Hepcon HMS Plus device or to standard weight and activated clotting time (ACT) based dosing. Blood samples were collected before and 10 minutes, 2 hours and 4 hours after cardiopulmonary bypass. Primary endpoint was endogenous thrombin potential in plasma 2 hours after surgery as assessed by calibrated automated thrombography. Secondary endpoints included total heparin and protamine doses, whole blood clot formation (thromboelastometry) and post-operative bleeding volume and transfusions. Heparin effect was assessed by measuring anti-Xa activity.Endogenous thrombin potential and clot formation deteriorated in both groups after surgery without statistically significant intergroup difference. There were no significant differences between the groups in total heparin and protamine doses, heparin effect, or postoperative bleeding and transfusions at any time point. Significant inverse correlations between anti-Xa activity and endogenous thrombin potential were observed 10 min (r = -0.43, p = 0.001), 2 hours (r = -0.66, p

Atherosclerotic cardiovascular diseases are the leading causes of morbidity and mortality worldwide. We have previously shown that arachidonate 15-lipoxygenase B (ALOX15B) is highly expressed in atherosclerotic carotid plaques, and elucidation of mechanisms downstream of activated lipoxygenases may be relevant to our understanding of the genesis of atherosclerotic diseases. We examined 120 carotid plaques from patients with symptomatic carotid artery stenosis and showed that the extent of ALOX15B staining was significantly increased in carotid plaques with thrombosis. Impedance aggregometry analyses showed that the ALOX15B enzyme products 15-HETE and 15-HPETE increased platelet aggregation. By using a calibrated automatic thrombin assay, we showed that the ALOX15B products also increased both peak levels of thrombin and the total endogenous thrombin potential. Moreover, platelet aggregation was increased by addition of cell lysates from ischemic human macrophages, whereas platelet aggregation was reduced after knockdown of ALOX15B in human macrophages. Our data show that ALOX15B expression in human carotid plaques is associated with thrombus formation and that enzyme products of ALOX15B increase platelet aggregation and thrombin generation. We therefore propose that activated ALOX15B in macrophages may play a role in the induction of atherothrombotic events by increasing platelet aggregation and thrombin generation.

INTRODUCTION: Cardiovascular diseases are a public health concern everywhere, especially ischemic or coronary heart diseases (CHD) which are on top of causes list of mortality and morbidity in both genders globally. From which nearly 80% can be because of modifiable risks. In Egypt, there is a lack of studies on the knowledge of people about coronary heart diseases and its modifiable risks. So, this research reported here we designed to measure the dimensions of peoples knowledge about CHD and their attitude towards prevention, and to identify the main risk reduction barriers. METHODS: By using comprehensive cross-sectional, descriptive research design, all adult individuals attending the family health clinic at Suez Canal University Hospital were eligible for inclusion with total number 125 participants. An interview questionnaire designed and used to collect data. RESULTS: The study revealed that (10.4%) of participants had a history of CHD, and (7.2%) had a family history of CHD. 79.2% Had a satisfactory total knowledge about CHD, and (94.4%) had a positive total attitude towards prevention. Risk reduction barriers as a medical setting barriers were (24%), patient related barriers were (22.4%). Community-societal barriers were almost the same as knowledge barriers which were around (16%). At last the systemic-organizational barriers were (9.6%). CONCLUSION: The findings settled that, total knowledge about CHD was satisfactory but lower than the level total of attitude. More effort the health system needs to improve the settings and engage patients in their plans and breaking related barriers, with development of health education programs based on needs assessment. Further studies we recommend to explore the reasons and follow up the changes.

A new influenza virus that was first detected in people in April 2009, was initially referred to colloquially as "swine flu", since it contained genes from swine, avian and human influenza viruses. It can, however, not be transmitted by eating pork or dealing with pigs. In Egypt, several hundred thousand pigs were killed in May, in spite of advice from global health authorities that such an action was unnecessary. Pigs are raised and consumed mainly by the Christian minority, which constitute some 10 % of the population. Health Ministry estimated there were between 300,000-350,000 pigs in Egypt. This paper will analyze the Egyptian health policy for controlling the pandemic H1N1 flu, exploring its context, content, process, and actors. The analysis is based on the Leichter Context, which refers to systemic factors-political, economic and social, both national and international-that may have an effect on health policy, and is based on data collected from literature review and policy documents. The International health officials said the swine flu virus that has caused worldwide fear is not transmitted by pigs, and that pig slaughters do nothing to stop its spread. The WHO stopped using the term "swine flu" to avoid confusion. In Egypt, even the editor of a pro-government newspaper criticized the order to slaughter: "Killing (pigs) is not a solution, otherwise, we should kill the people, because the virus spreads through them," wrote Abdullah Kamal of the daily Rose El-Youssef. The World Health organization also criticized the decision. The extinction of the Egyptian pigs is an example of how a health issue can be used to persecute a minority within a country. Although the current influenza has nothing whatsoever to do with pigs, the previous name of the epidemic was used as an argument to violate the rights of the Christian minority in Egypt.