29. No association between MTHFR C677T polymorphism and congenital heart disease in Saudi Arabian population

Congenital heart diseases (CHD) are the most common birth defects in the world. It is a major cause of childhood mortality and morbidity worldwide with about 7 per 1000 live birth. Studies suggest that Methylenetetrahydrofolate reductase (MTHFR) polymorphism C667T has been associated with congenital malformation; this common missense mutation in the MTHFR gene may reduce enzymatic action, and may be involved in the etiology of congenital heart defects (CHD), but the evidence remains inconclusive. The aim of this study is to determine whether this association exists in the Saudi Arabian population.MethodDNA sequencing was used to detect genotype MTHFR C677T in 75 CHD patients and 100 ethnically similar controls. The type of cardiac defect was diagnosed by cardiovascular specialist and confirmed by echocardiographic.ResultsThe distribution of the MTHFR 677C >T SNP genotypes and alleles in both CHD and control groups were 70.0% CC, 26.0% CT, 4.0% TT in cases and 70.8% CC, 25.4% CT, 3.8% TT in controls. The T allele frequency was 17.0% in cases and 16.5% in controls. The difference between genotypes and alleles was not statistically significant between controls and the CHD groups.ConclusionWe did not find sufficient evidence for an association between MTHFR C677T genotype and congenital heart disease in Saudi Arabian population. We agree that the sample size is a limitation to our above conclusions

The Immunomodulatory Role of Microbiota in Rheumatic Heart Disease: What Do We Know and What Can We Learn from Other Rheumatic Diseases?

Rheumatic heart disease (RHD) represents a serious cardiac sequela of acute rheumatic fever, occurring in 30-45% of patients. RHD is multifactorial, with a strong familial predisposition and known environmental risk factors that drive loss of immunological tolerance. The gut and oral microbiome have recently been implicated in the pathogenesis of RHD. Disruption of the delicate balance of the microbiome, or dysbiosis, is thought to lead to autoimmune responses through several different mechanisms including molecular mimicry, epitope spreading, and bystander activation. However, data on the microbiomes of RHD patients are scarce. Therefore, in this comprehensive review, we explore the various dimensions of the intricate relationship between the microbiome and the immune system in RHD and other rheumatic diseases to explore the potential effect of microbiota on RHD and opportunities for diagnosis and treatment.This publication was supported by Qatar University, internal grant no. QUCP-CHS-2022-551 and QU Health cluster, Qatar University. The findings achieved herein are solely the responsibility of the authors.Scopu

The polymorphism at the microRNA-155 binding site in AGTR1 gene is not significantly associated with rheumatic heart disease in Saudi Arabia population

Rheumatic heart disease (RHD) remains a major cause of cardiovascular diseases and the most devastating effects are on children and young adults. RHD is caused due to the interaction between microbial, environmental, immunologic, and genetic factors. The renin-angiotensin aldosterone system (RAAS) has been strongly implicated as the susceptibility pathway in the pathogenesis of cardiovascular disease. The present study investigated the modulating effect of Angiotensin II type 1 receptor (AGTR1) 1166A>C polymorphism on the RHD and its clinical features in Saudi Arabia. AGTR1 1166A>C polymorphism was genotyped in 96 echocardiographically confirmed RHD patients and 142 ethnically matched controls by TaqMan allelic discrimination method. Genotype distribution of the AGTR1 1166A>C polymorphism was not significantly different between RHD and control groups. Further, AGTR1 1166A>C genotypes are not associated with the clinical features of RHD. These data support that there was no evidence for an association between AGTR1 1166A>C polymorphism and RHD in Saudi Arabia. To our knowledge, this is the first study that has investigated the possible association between AGTR1 1166A>C polymorphism and susceptibility to RHD and its clinical features. Even though AGTR1 gene is 1166A>C (rs5186) was reported to be associated with hypertension, left ventricular hypertrophy and coronary heart disease. Present study did not find any association between AGTR1 1166A>C polymorphism and RHD in Saudi Arabia. Further studies are needed to confirm our findings

Impact of MIF Gene Promoter Variations on Risk of Rheumatic Heart Disease and its Age of Onset in Saudi Arabian Patients

Although macrophage migration inhibitory factor (MIF) has consistently been shown to be an important immune modulator, data on the association between MIF promoter variations and the risk of developing rheumatic heart disease (RHD) remain inconclusive. RHD remains an important complication of streptococcal infections in the Middle East, not least in Saudi Arabia, and identifying risk markers remains an important priority. Therefore, we investigated the association between two functional MIF promoter variations and RHD susceptibility and severity in Saudi patients: the MIF-173G>C substitution (rs755622) and the MIF-794 CATT5-8 tetra-nucleotide repeat (rs5844572). 326 individuals (124 RHD patients and 202 age-, sex-, and ethnically-matched healthy controls) were genotyped using allelic discrimination and fragment analysis. Data were analyzed with respect to disease susceptibility, severity, sex, and age of onset. There was a significantly lower frequency of 173C allele carriage in RHD patients compared to controls (OR = 0.47; 95% CIs = 0.28-0.77; p = 0.003). Interestingly, the 173C allele was associated with late disease onset (p = 0.001). The 794 5-repeat allele was associated with decreased RHD risk (OR = 0.56; 95% CIs = 0.38-0.82; p = 0.003). In contrast, the 794 6-repeat allele was associated with increased risk of RHD (OR = 1.7; 95% CIs = 1.2-2.5; p = 0.002). MIF promoter variations appear to have a dual role in RHD, with 173C allele non-carriers at higher risk of developing RHD at a younger age. These results require further validation in larger multi-ethnic cohorts, and functional studies are necessary to understand the underlying molecular mechanisms driving the at-risk phenotype

Association between β-blocker use and mortality in critically ill patients: a nested cohort study

Abstract Background β-blockers have several indications in critically ill patients and are commonly used. The aim of this study is to examine the relationship between the use of β-blockers in critically ill patients and mortality. Methods This was a nested cohort study in which all medical-surgical ICU patients (N = 523) enrolled in a randomized clinical trial of intensive insulin therapy (ISRCTN07413772) were grouped according to β-blocker use during ICU stay. To account for the indication of β-blockers, we constructed a propensity score using selected clinically-relevant and statistically-significant variables related to β-blocker exposure and outcome. The primary endpoints were all-cause ICU and hospital mortality. Secondary endpoints were the development of severe sepsis during ICU stay, ICU and hospital length of stay, and mechanical ventilation duration. Using multivariable models, we adjusted the associations of β-blockers and these outcomes to the propensity score. Results Of the 523 patients enrolled in the study, 89 (17.0%) received β-blockers during their ICU stay. There were no significant associations between β-blocker therapy and ICU mortality (adjusted odds ratio [aOR] 1.56, 95% confidence interval [CI] 0.83–2.9, P = 0.16), hospital mortality (aOR 1.09, 95% CI 0.99–1.20, P = 0.73), the risk of ICU-acquired severe sepsis (aOR 1.67, 95% CI 0.95–2.97, P = 0.08), mechanical ventilation duration (P = 0.17), or ICU length of stay (P = 0.22). However, β-blocker use was associated with increased ICU and hospital mortality among nondiabetic patients (aOR 2.93, 95% CI 1.19–7.23, and 2.43, 95% CI 1.05–5.64, respectively). Conclusions Our study showed that β-blockers during the ICU stay had no significant association with mortality or morbidity. However, β-blocker therapy was associated with increased mortality in non-diabetic patients. Trial registration ISRCTN07413772; (dated 13.07.2005)

A cross-sectional study factors associated with resilience among medical staff in radiology departments during COVID-19, Riyadh, Kingdom of Saudi Arabia

Objectives This study aims to assess the level of resilience of medical workers in radiology departments in Riyadh, Kingdom of Saudi Arabia, during the COVID-19 outbreak and to explore associated factors.Setting Medical staff, including nurses, technicians, radiology specialists and physicians, working in radiology departments at government hospitals in Riyadh, Saudi Arabia during the COVID-19 outbreak.Design A cross-sectional study.Participants The study was conducted among 375 medical workers in radiology departments in Riyadh, Kingdom of Saudi Arabia. The data collection took place from 15 February 2022 to 31 March 2022.Results The total resilience score was 29.37±6.760 and the scores of each dimension showed that the higher mean score was observed in the domain of ‘flexibility’, while the lowest was observed in ‘maintaining attention under stress’. Pearson’s correlation analysis showed that there was a significant negative correlation between resilience and perceived stress (r=–0.498, p<0.001). Finally, based on multiple linear regression analysis, factors affecting resilience among participants are the availability of psychological hotline (available, B=2.604, p<0.050), knowledge of COVID-19 protective measures (part of understanding, B=−5.283, p<0.001), availability of adequate protective materials (partial shortage, B=−2.237, p<0.050), stress (B=−0.837, p<0.001) and education (postgraduate, B=−1.812, p<0.050).Conclusions This study sheds light on the level of resilience and the factors that contribute to resilience in radiology medical staff. Moderate levels of resilience call for health administrators to focus on developing strategies that can effectively help cope with workplace adversities