Major Cardiovascular Advances: Highlights from the 2019 American College of Cardiology Annual Scientific Session

The 69th American College of Cardiology Annual Scientific Session and Expo was held in New Orleans, Louisiana on March 16–18, 2019. For many years this meeting has gathered together an enormous number of participants, abstracts, oral presentations, poster presentations, educational sessions, late-breaking clinical trial results, and clinical practice guidelines under one roof. The authors have selected and summarized the key points from a number of key landmark trials, featured clinical research results and clinical practice guidelines that were presented during this year’s meeting

Cardiac Inflammation, Oxidative Stress, Nrf2 Expression, and Coagulation Events in Mice with Experimental Chronic Kidney Disease

Chronic kidney disease (CKD) is known to be associated with cardiovascular dysfunction. Dietary adenine intake in mice is also known to induce CKD. However, in this experimental model, the mechanisms underlying the cardiotoxicity and coagulation disturbances are not fully understood. Here, we evaluated cardiac inflammation, oxidative stress, DNA damage, and coagulation events in mice with adenine (0.2% w/w in feed for 4 weeks)-induced CKD. Control mice were fed with normal chow for the same duration. Adenine increased water intake, urine output, relative kidney weight, the plasma concentrations of urea and creatinine, and the urinary concentrations of kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin. It also decreased the body weight and creatinine clearance, and caused kidney DNA damage. Renal histological analysis showed tubular dilation and damage and neutrophilic influx. Adenine induced a significant increase in systolic blood pressure and the concentrations of troponin I, tumor necrosis factor-α, and interleukin-1β in heart homogenates. It also augmented the levels of markers of lipid peroxidation measured by malondialdehyde production and 8-isoprostane, as well as the antioxidants superoxide dismutase and catalase. Immunohistochemical analysis of the hearts showed that adenine increased the expression of nuclear factor erythroid-derived 2-like 2 by cardiomyocytes. It also caused cardiac DNA damage. Moreover, compared with the control group, adenine induced a significant increase in the number of circulating platelet and shortened the thrombotic occlusion time in pial arterioles and venules in vivo, and induced a significant reduction in the prothrombin time and activated partial thromboplastin time. In conclusion, the administration of adenine in mice induced CKD-associated cardiac inflammation, oxidative stress, Nrf2 expression, and DNA damage. It also induced prothrombotic events in vivo. Therefore, this model can be satisfactorily used to study the cardiac pathophysiological events in subjects with CKD and the effect of drug treatment thereon

PHYSICIAN AS A MANAGER: PERSONAL AND MANAGERIAL CHARCTERISTICS, SAUDI ARABIA

BACKGROUND: The emergence of physicians' roles in key adminstrative positions within many King Saudi Arabia health care organizations has represented a major change in the medical profession over the last two decades. This have created a need for physicians who are willing to assume a high level of responsibility for managing evovling health care organizations. The study explores the perception of physician managers regarding their work, personal and managerial characteristics. METHODS: The data for this study were obtained from a sample of 200 physicians working in management positions in different health care organizations in Riyadh. Physicians were selected at random with probability proportional to size from a list containing managers in all health care organization to participate in the study RESULTS: Our results indicated that physician managers lack admistration skills. No formal training in medical adminstration and management because management principles are not integrated in the medical context and the majority were experienced in management for less than four years.  Very few possess the technical comptencies such as strategic planning, financial and economics knowledge. Boredom with medical practice, improvement of personal position and encouragement from others are related to being older, having more years in medicine and interest in medicine is reduced. The finding also supported the notion that physician manager can maintain stable levels of loyality to professional interest and organization. This dual commitment is related to work-relate characteristics involving sharing his time favorably to management job and to patient care. Recommendation: To improve their management skills physicians can benefit from mamagement education programs such as those offered by King Saud University

Exercise Training Mitigates Water Pipe Smoke Exposure-Induced Pulmonary Impairment via Inhibiting NF- κ

Water pipe smoking is a tobacco smoking method commonly used in Eastern countries and is gaining popularity in Europe and North America, in particular among adolescents and young adults. Several clinical and experimental studies have reported that exposure to water pipe smoke (WPS) induces lung inflammation and impairment of pulmonary function. However, the mechanisms of such effects are not understood, as are data on the possible palliative effect of exercise training. The present study evaluated the effects of regular aerobic exercise training (treadmill: 5 days/week, 40 min/day) on subchronic exposure to WPS (30 minutes/day, 5 days/week for 2 months). C57BL/6 mice were exposed to air or WPS with or without exercise training. Airway resistance measured using forced oscillation technique was significantly and dose-dependently increased in the WPS-exposed group when compared with the air-exposed one. Exercise training significantly prevented the effect of WPS on airway resistance. Histologically, the lungs of WPS-exposed mice had focal moderate interstitial inflammatory cell infiltration consisting of neutrophil polymorphs, plasma cells, and lymphocytes. There was a mild increase in intra-alveolar macrophages and a focal damage to alveolar septae in some foci. Exercise training significantly alleviated these effects and also decreased the WPS-induced increase of tumor necrosis factor α and interleukin 6 concentrations and attenuated the increase of 8-isoprostane in lung homogenates. Likewise, the lung DNA damage induced by WPS was significantly inhibited by exercise training. Moreover, exercise training inhibited nuclear factor kappa-B (NF-κB) expression induced by WPS and increased that of nuclear factor erythroid 2-related factor 2 (Nrf2). Our findings suggest that exercise training significantly mitigated WPS-induced increase in airway resistance, inflammation, oxidative stress, and DNA damage via mechanisms that include inhibiting NF-κB and activating Nrf2 signalling pathways

Gum Arabic Ameliorates Impaired Coagulation and Cardiotoxicity Induced by Water-Pipe Smoke Exposure in Mice

Water-pipe smoking (WPS) is prevalent in the East and elsewhere. WPS exposure is known to induce thrombosis and cardiovascular toxicity involving inflammation and oxidative stress. Here, we have investigated the effect of Gum Arabic (GA), a prebiotic with anti-oxidant, anti-inflammatory and cytoprotective properties, on WPS exposure (30 min/day for 1 month) on coagulation and cardiac homeostasis, and their possible underlying mechanisms in mice. Animals received either GA in drinking water (15%, w/v) or water only for the entire duration of study. GA significantly mitigated thrombosis in pial microvessels in vivo, platelet aggregation in vitro, and the shortening of prothrombin time induced by WPS exposure. The increase in plasma concentrations of fibrinogen, plasminogen activator inhibitor-1 and markers of lipid peroxidation, 8-isoprostane and malondialdehyde, induced by WPS were significantly reduced by GA administration. Moreover, WPS exposure induced a significant increase in systolic blood pressure and the concentrations of the pro-inflammatory cytokines tumor necrosis factor-α and interleukin 1β in heart homogenates. GA significantly alleviated these effects, and prevented the decrease of reduced glutathione, catalase and total nitric oxide levels in heart homogenates. Immunohistochemical analysis of the hearts showed that WPS exposure increased nuclear factor erythroid-derived 2-like 2 (Nrf2) expressions by cardiac myocytes and endothelial cells, and these effects were potentiated by the combination of GA and WPS. WPS also increased DNA damage and cleaved caspase 3, and GA administration prevented these effects. Our data, obtained in experimental murine model of WPS exposure, show that GA ameliorates WPS-induced coagulation and cardiovascular inflammation, oxidative stress, DNA damage and apoptosis, through a mechanism involving Nrf2 activation

Influence of Monomer Systems on the Bond Strength Between Resin Composites and Polymerized Fiber-Reinforced Composite upon Aging

Purpose: This study examined the influence of different monomer systems on the tensile bond strength between a resin composite and a polymerized fiber-reinforced composite (FRC). The influence of the age (shelf-life) of the FRC prepreg (reinforcing fiber pre-impregnated with a resin system) before preparing the FRC substrate for the bonding test was also assessed.Materials and Methods: Semi-interpenetrating polymer network (semi-IPN)-based glass FRC prepregs were aged for various durations (1, 1.5, and 3 years) at 4 degrees C before being used to prepare FRC substrates via light polymerization. Four groups of aged prepregs were prepared through different treatments with: 1. no primer; 2. a dimethacrylate-based adhesive primer; 3. a universal primer; and 4. a specific composite primer. Subsequently, a resin composite luting cement was applied on the treated FRC substrates and cured with light. The water sorption of the FRC-composite specimens was determined. Then, the differences in the tensile bond strength were evaluated using ANOVA (p <= 0.05).Results: There were significant differences in the tensile bond strength between the composite cement and the FRC according to the primer used (p < 0.001), aging time (p < 0.001), and their interactive effect (p < 0.001).Conclusion: The monomers of the universal primer demonstrated the best ability to diffuse into the semi-IPN structure of the polymer matrix of FRC. This improved the interfacial bond strength between the composite cement and the FRC substrate

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Protective Effect of Curcumin on Pulmonary and Cardiovascular Effects Induced by Repeated Exposure to Diesel Exhaust Particles in Mice

Particulate air pollution has been associated with increased risk of cardiopulmonary diseases. However, the underlying mechanisms are not fully understood. We have previously demonstrated that single dose exposure to diesel exhaust particle (DEP) causes lung inflammation and peripheral thrombotic events. Here, we exposed mice with repeated doses of DEP (15µg/animal) every 2nd day for 6 days (a total of 4 exposures), and measured several cardiopulmonary endpoints 48 h after the end of the treatments. Moreover, the potential protective effect of curcumin (the yellow pigment isolated from turmeric) on DEP-induced cardiopulmonary toxicity was assessed. DEP exposure increased macrophage and neutrophil numbers, tumor necrosis factor α (TNF α) in the bronchoalveolar lavage (BAL) fluid, and enhanced airway resistance to methacoline measured invasively using Flexivent. DEP also significantly increased plasma C-reactive protein (CRP) and TNF α concentrations, systolic blood pressure (SBP) as well as the pial arteriolar thrombosis. It also significantly enhanced the plasma D-dimer and plasminogen activator inhibitor-1 (PAI-1). Pretreatment with curcumin by oral gavage (45 mg/kg) 1h before exposure to DEP significantly prevented the influx of inflammatory cells and the increase of TNF α in BAL, and the increased airway resistance caused by DEP. Likewise, curcumin prevented the increase of SBP, CRP, TNF α, D-dimer and PAI-1. The thrombosis was partially but significantly mitigated. In conclusion, repeated exposure to DEP induced lung and systemic inflammation characterized by TNFα release, increased SBP, and accelerated coagulation. Our findings indicate that curcumin is a potent anti-inflammatory agent that prevents the release of TNFα and protects against the pulmonary and cardiovascular effects of DEP