| 1. |
- Aburawi, Elhadi H., et al.
(author)
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Epigenetics of conotruncal congenital heart disease : Protocol for a systematic review and meta-analysis
- 2024
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:4
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Research review (peer-reviewed)abstract
- BACKGROUND: Conotruncal congenital heart defects (CTD) are a subset of congenital heart diseases (CHD) that involve structural anomalies of the right, left, or both cardiac outflow tracts. CHD is caused by multifactorial inheritance and changes in the genes or chromosomes. Recently, CHD was found to be due to epigenetic alterations, which are a combination of genetic and other environmental factors. Epigenetics is the study of how a gene's function changes as a result of environmental and behavioral influences. These causative factors can indirectly cause CHD by altering the DNA through epigenetic modifications. This is a protocol for a systematic review and meta-analysis that aims to explore whether the strength of association between various epigenetic changes and CTD types varies by race. Furthermore, to determine and compare the changes in gene expression of each mutation.METHODS: Our protocol follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) guidelines. A comprehensive pre-search has been developed in PubMed and PubMed's Medical Subject Headings (MeSH). The final search will be performed in June 2023 in PubMed, Embase, Scopus, Web of Science, Cochrane Library, CIANHL, and PsycInfo, without restrictions on publication years. The Covidence systematic review software will be used for blinded screening and selection. Conflicts will be resolved by a third, independent reviewer. The risk of bias in selected studies will be assessed using the National Heart, Lung, and Blood Institute (NHLBI) Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. The data to be extracted will cover basic information on the included studies, study sample size, number of patients with various types of epigenetic changes, number of patients with various CTD types, measures of association and their 95% confidence interval between each epigenetic change and each CTD. The protocol has been registered with the International Prospero Register of Systematic Review (PROSPERO) [CRD42023377597].DISCUSSION: To the best of our knowledge, this protocol outlines the first systematic review and meta-analysis of the epigenetics of CTD. There is a growing body of evidence on epigenetics and its indirect involvement in disease by altering the DNA through epigenetic modifications in the genes associated with the causative factors for CHD. We will conduct a comprehensive and systematic search for literature in the above-mentioned seven core biomedical databases. It is very important to identify population-specific risk factors for CHD, which will have significant creative, custom-made, and effective prevention programs for the future generation.
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| 2. |
- Alfalasi, Maryam, et al.
(author)
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Effect of Nitric Oxide Pathway Inhibition on the Evolution of Anaphylactic Shock in Animal Models : A Systematic Review
- 2022
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In: Biology. - : MDPI. - 2079-7737. ; 11:6
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Research review (peer-reviewed)abstract
- Simple Summary: Anaphylactic shock (AS) is the most serious consequence of anaphylaxis, with life-threatening sequelae including hypovolemia, shock, and arrhythmias. The literature lacks evidence for the effectiveness of interventions other than epinephrine in the acute phase of anaphylaxis. Our objective was to assess, through a systematic review, how inhibition of nitric oxide (NO) pathways affects blood pressure, and whether such blockade improves survival in AS animal models. AS was induced in all included studies after or before drug administration that targeted blockade of the NO pathway. In all animal species studied, the induction of AS caused a reduction in arterial blood pressure. However, the results show different responses to the inhibition of nitric oxide pathways. Overall, seven of fourteen studies using inhibition of nitric oxide pathways as pre-treatment before induction of AS showed improvement of survival and/or blood pressure. Four post-treatment studies from eight also showed positive outcomes. This review did not find strong evidence to propose modulation of blockade of the NO/cGMP pathway as a definitive treatment for AS in humans. Well-designed in vivo AS animal pharmacological models are needed to explore the other pathways involved, supporting the concept of pharmacological modulation.Abstract: Nitric oxide (NO) induces vasodilation in various types of shock. The effect of pharmacological modulation of the NO pathway in anaphylactic shock (AS) remains poorly understood. Our objective was to assess, through a systematic review, whether inhibition of NO pathways (INOP) was beneficial for the prevention and/or treatment of AS. A predesigned protocol for this systematic review was published in PROSPERO (CRD42019132273). A systematic literature search was conducted till March 2022 in the electronic databases PubMed, EMBASE, Scopus, Cochrane and Web of Science. Heterogeneity of the studies did not allow meta-analysis. Nine hundred ninety unique studies were identified. Of 135 studies screened in full text, 17 were included in the review. Among six inhibitors of NO pathways identified, four blocked NO synthase activity and two blocked guanylate cyclase downstream activity. Pre-treatment was used in nine studies and post-treatment in three studies. Five studies included both pre-treatment and post-treatment models. Overall, seven pre-treatment studies from fourteen showed improvement of survival and/or arterial blood pressure. Four post-treatment studies from eight showed positive outcomes. Overall, there was no strong evidence to conclude that isolated blockade of the NO/cGMP pathway is sufficient to prevent or restore anaphylactic hypotension. Further studies are needed to analyze the effect of drug combinations in the treatment of AS.
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| 3. |
- Lauque, Dominique, et al.
(author)
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Length-of-Stay in the Emergency Department and In-Hospital Mortality : A Systematic Review and Meta-Analysis
- 2022
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In: Journal of Clinical Medicine. - : MDPI. - 2077-0383. ; 12:1
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Research review (peer-reviewed)abstract
- The effect of emergency department (ED) length of stay (EDLOS) on in-hospital mortality (IHM) remains unclear. The aim of this systematic review and meta-analysis was to determine the association between EDLOS and IHM. We searched the PubMed, Medline, Embase, Web of Science, Cochrane Controlled Register of Trials, CINAHL, PsycInfo, and Scopus databases from their inception until 14-15 January 2022. We included studies reporting the association between EDLOS and IHM. A total of 11,337 references were identified, and 52 studies (total of 1,718,518 ED patients) were included in the systematic review and 33 in the meta-analysis. A statistically significant association between EDLOS and IHM was observed for EDLOS over 24 h in patients admitted to an intensive care unit (ICU) (OR = 1.396, 95% confidence interval [CI]: 1.147 to 1.701; p < 0.001, I2 = 0%) and for low EDLOS in non-ICU-admitted patients (OR = 0.583, 95% CI: 0.453 to 0.745; p < 0.001, I2 = 0%). No associations were detected for the other cut-offs. Our findings suggest that there is an association between IHM low EDLOS and EDLOS exceeding 24 h and IHM. Long stays in the ED should not be allowed and special attention should be given to patients admitted after a short stay in the ED.
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| 4. |
- Aburawi, Elhadi H., et al.
(author)
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Effects of N-3 Polyunsaturated Fatty Acids on Left Ventricular Function and Coronary Flow in Children with Type 1 Diabetes Mellitus
- 2011
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In: Pediatric Research. - : Springer Science and Business Media LLC. - 1530-0447 .- 0031-3998. ; 70:227
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Conference paper (peer-reviewed)abstract
- Purposes: Dietary supplementation with N-3 Polyunsaturated Fatty Acids (n-3 PUFAs) could have beneficial effects on cardiovascular system in patients with type 1 diabetes mellitus (DM1). Methods: In a double-blind placebo controlled crossover study, 33 children with DM1 duration of more than one year were randomly and equally assigned to either n-3 PUFAs (2 gm/day, Nycoplus® Omega-3, 1000 mg) or placebo treatment for 8 weeks. Following a 4-week period recovery, the groups were crossovered with above treatments for another 8 weeks. Transthoracic Doppler echocardiography (TTDE) study was done on pre and post treatment visits, and after one month's treatment free recovery for left ventricular function and flow in the left anterior descending coronary artery (LAD). Results: Of recruited children 28 (85%) completed the study. n-3 PUFAs treatment was associated with increase in mean cardiac index (CI; from 2.7±0.4 to 3.7±0.8 l/min/m2, p< 0.0001) and left ventricular fractional shortening (FS; from 31±2.5 to 39±3%, p< 0.0001). The treatment decreased both LAD peak flow velocity (PFVd) from 96±17 to 68±12 cm/s, p< 0.0001 and LAD CF from 105±31 to 66±15 ml/min, p< 0.0001). One month after stopping the treatment CI decreased from 3.7±0.8 to 2.6±0.5 l/min/m2, p< 0.0001 and mean FS from 39±3 to 32±2, p< 0.0001. Mean PFVd increased from 68±12 to 90±12 cm/s, p< 0.0001 and CF from 66±15 to 108±30 ml/min, p< 0.0001. Conclusions: In patients with DM1 n-3 PUFA therapy increased cardiac index and LV systolic function. The basal coronary flow decrease improving the circumstances for better coronary flow reserve.
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| 5. |
- Liuba, Petru, et al.
(author)
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Coronary flow and reactivity, but not arrhythmia vulnerability, are affected by cardioplegia during cardiopulmonary bypass in piglets
- 2013
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In: Journal of Cardiothoracic Surgery. - : Springer Science and Business Media LLC. - 1749-8090. ; 8
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Journal article (peer-reviewed)abstract
- Background: Surgery under cardiopulmonary bypass (CPB) is still associated with significant cardiovascular morbidity in both pediatric and adult patients but the mechanisms are not fully understood. Abnormalities in coronary flow and function have been suggested to play an important role. Prior studies suggest protective effects on coronary and myocardial function by short intravenous (i.v.) infusion of cyclosporine A before CPB. Methods: Barrier-bred piglets (10-12 kg, n=20) underwent CPB for 45 min, with or without antegrade administration of cardioplegic solution. Prior to CPB, half of the animals in each group received an i.v. infusion of 100 mg/kg cyclosporine A. The left anterior descending coronary flow velocity responses to adenosine, serotonin, and atrial pacing, as well as left ventricular function and postsurgical vulnerability to atrial fibrillation (Afib) were assessed by intracoronary Doppler, epicardial echocardiography, and in vivo electrophysiological study, before and 8 hours after surgery. Plasma C-reactive protein (CRP) and fibrinogen were measured at both time-points. Results: Cyclosporine infusion did not influence any of the studied variables (p>0.4). Coronary peak flow velocity (cPFV) rose significantly after surgery especially in the cardioplegia group (p<0.01 vs. non-cardioplegia group and pre-surgery). cPFV responses to adenosine, but not to serotonin, tended to decrease (p=0.06) after surgery only in cardioplegia group (p=0.06; p=0.8 in non-cardioplegia group vs pre-surgery). Also, cPFV response to atrial pacing was lower in the cardioplegia than in the non-cardioplegia group (p=0.02). Neither vulnerability nor duration of induced Afib after CPB differed between groups (Chi-square p=0.4). Cyclosporine had no significant effect on coronary indexes or arrhythmia vulnerability (p>0.4). There was no difference in systolic myocardial function between groups at any time point. Conclusion: In piglets, CPB with cardioplegia was associated with profound abnormalities in coronary vasomotor tone and receptor-related flow regulation, whereas arrhythmia vulnerability appeared to be comparable with that in non-cardioplegia group. In this study, preconditioning with cyclosporine had no detectable protective effect on coronary circulation or arrhythmia vulnerability after CPB.
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| 6. |
- Pesonen, Erkki, et al.
(author)
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Review findings included diminished coronary flow reserve after surgery in children with congenital heart disease and inflammation
- 2019
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In: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253. ; 108:2, s. 218-223
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Journal article (peer-reviewed)abstract
- Aim: The aim of this review was to develop a deeper knowledge of the physiology of coronary blood flow and coronary flow reserve in young patients with congenital heart disease and inflammatory diseases. Methods: We searched for papers published in English on coronary blood flow and coronary flow reserve using the PubMed and Google search databases. This identified 42 papers extending back to 1976 and a book from 2008 (Davis et al. Microcirculation. Boston, MA: Elsevier, 2008: 161–284). Results: Our review showed that the implications of coronary blood flow and coronary flow reserve in paediatric patients with congenital heart disease and inflammatory diseases are still not fully understood. However, a key finding was that coronary flow reserve was diminished in patients with congenital heart disease and inflammation after surgery, with or without a cardiopulmonary bypass. Other findings discussed by this review relate to volume and pressure overload in acyanotic congenital heart disease, reduced myocardial perfusion and cyanotic congenital heart disease. Conclusion: We still have much to discover about paediatric patients with congenital heart disease and inflammatory diseases. Understanding the pathophysiology of coronary blood flow could help the postoperative treatment of such patients.
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