Quantification of hs-Troponin Levels and Global Longitudinal Strain among Critical COVID-19 Patients with Myocardial Involvement.

Background. Myocardial involvement among critically ill patients with coronavirus disease 2019 (COVID-19) often has worse outcomes. An imbalance in the oxygen supply causes the excessive release of pro-inflammatory cytokines, which results in increased ventilation requirements and the risk of death in COVID-19 patients. Purpose. We evaluated the association between the hs-troponin I levels and global longitudinal strain (GLS) as evidence of myocardial involvement among critical COVID-19 patients. Methods. We conducted a prospective cohort study from 1 February to 31 July 2021 at RSUD Dr. Soetomo, Surabaya, as a COVID-19 referral center. Of the 65 critical COVID-19 patients included, 41 (63.1%) were men, with a median age (interquartile range) of 51.0 years (20.0-75.0). Subjects were recruited based on WHO criteria for severe COVID-19, and myocardial involvement in the form of myocarditis was assessed using CDC criteria. Subjects were examined using echocardiography to measure the GLS, and blood samples were taken to measure the hs-troponin. Subjects were then followed for their need for mechanical ventilation and in-hospital mortality. Results. Severe COVID-19 patients with cardiac injury were associated with an increased need for intubation (78.5%) and an increased incidence of myocarditis (50.8%). There was a relationship between the use of intubation and the risk of death in patients (66.7% vs. 33.3%, p-value < 0.001). Decreased GLS and increased hs-troponin were associated with increased myocarditis (p values < 0.001 and 0.004, respectively). Decreased GLS was associated with a higher need for mechanical ventilation (12.17 + 4.79 vs. 15.65 + 4.90, p-value = 0.02) and higher mortality (11.36 + 4.64 vs. 14.74 + 4.82; p-value = 0.005). Elevated hs-troponin was associated with a higher need for mechanical ventilation (25.33% vs. 3.56%, p-value = 0.002) and higher mortality (34.57% vs. 5.76%, p-value = 0.002). Conclusions. Critically ill COVID-19 patients with myocardial involvement and elevated cardiac troponin levels are associated with a higher need for mechanical ventilation and higher mortality.

Analysis of the Effects of IL-6 -572 C/G, CRP -757 A/G, and CRP -717 T/C Gene Polymorphisms; IL-6 Levels; and CRP Levels on Chronic Periodontitis in Coronary Artery Disease in Indonesia.

Interleukin 6 (IL-6) and C-Reactive Protein (CRP) play an important role in chronic periodontitis with coronary artery disease (CAD). Genetic factors can affect a person's risk of CAD, which affects one-third of the population. This study investigated the role of IL-6 -572 C/G, CRP -757 A/G, and CRP -717 T/C gene polymorphisms. IL-6 and CRP levels on the severity of periodontitis in CAD in Indonesia were also evaluated. This case-control study was conducted with mild and moderate-severe chronic periodontitis groups. A path analysis test was conducted with Smart PLS with a 95% confidence interval to determine the significant variable for chronic periodontitis. Our study revealed that the effects of IL-6 -572 C/G, CRP -757 A/G, and CRP -717 T/C gene polymorphisms on IL-6 levels and CRP levels were not significant. IL-6 and CRP levels were not significantly different between the two groups. We found that IL-6 levels had a significant effect on CRP levels in periodontitis patients with CAD (path coefficient 0.322, p = 0.003). IL-6 -572 C/G, CRP -757 A/G, and CRP -717 T/C gene polymorphisms had no effect on the severity of chronic periodontitis in CAD patients in the Indonesian population. We also observed no apparent effects of the influence of gene polymorphisms in IL-6 -572 C/G, CRP -757 A/G, and CRP -717 T/C genes. Although the IL-6 and CRP levels were not significantly different between the two groups, IL-6 levels affected CRP levels in periodontitis patients with CAD.

Isolation and Culture of Non-adherent Cells for Cell Reprogramming.

Coronary heart disease (CHD) is a leading cause of death globally, while its current management is limited to reducing the myocardial infarction area without actually replacing dead cardiomyocytes. Direct cell reprogramming is a method of cellular cardiomyoplasty which aims for myocardial tissue regeneration, and CD34+ cells are one of the potential sources due to their shared embryonic origin with cardiomyocytes. However, the isolation and culture of non-adherent CD34+ cells is crucial to obtain adequate cells for high-efficiency genetic modification. This study aimed to investigate the optimal method for isolation and culture of CD34+ peripheral blood cells using certain culture media. A peripheral blood sample was obtained from a healthy subject and underwent pre-enrichment, isolation, and expansion. The culture was subsequently observed for their viability, adherence, and confluence. Day 0 observation of the culture showed a healthy CD34+ cell with a round cell shape, without any adherent cells present yet. Day 4 of observation showed that CD34+ cells within the blood plasma medium became adherent, indicated by their transformations into spindle or oval morphologies. Meanwhile, CD34+ cells in vitronectin and fibronectin media showed no adherent cells and many of them died. Day 7 observation revealed more adherent CD34+ cells in blood plasma medium, and which had 75% of confluence. In conclusion, the CD34+ cells that were isolated using a combination of density and magnetic methods may be viable and adequately adhere in culture using blood plasma medium, but not in cultures using fibronectin and vitronectin.

The Role of Plasma Interleukin-6 Levels on Atherosclerotic Cardiovascular Disease and Cardiovascular Mortality Risk Scores in Javanese Patients with Chronic Kidney Disease.

Interleukin-6 (IL-6) has been identified as an important pro-inflammatory factor involved in mediating the severity of chronic kidney disease (CKD). This study sought to determine the effect of plasma IL-6 levels on atherosclerotic cardiovascular disease (ASCVD) and cardiovascular mortality risk scores in Javanese CKD patients. We also analyzed the frequency of IL-6 G174C single nucleotide polymorphism (SNP) in the population. This study was a cross-sectional study involving seventy-three patients of Javanese ethnic origin with stable chronic kidney disease. We assessed the ASCVD risk score, cardiovascular mortality score, genotyping of IL-6 G174C SNP, and plasma IL-6 levels in these patients. The genotype distribution and allele frequencies of the IL-6 G174C SNP were predominated by the G genotype/allele (GG: 97.26%, GC: 1.37%, CC: 1.37%, G-allele: 97.95%, and C-allele: 2.05%). Despite the fact that plasma IL-6 levels did not directly affect cardiovascular mortality risk, further analysis revealed its direct effect on the ASCVD risk score (path coefficient = 0.184, p = 0.043, 95% CI = 0.018−0.380), which in turn affected cardiovascular mortality risk (path coefficient = 0.851, p = <0.01, 95% CI = 0.714−0.925). In conclusion, plasma IL-6 levels play important roles on ASCVD risk and cardiovascular mortality risk in Javanese patients with CKD.

The Effect of Angiotensin Converting Enzyme (ACE) I/D Polymorphism on Atherosclerotic Cardiovascular Disease and Cardiovascular Mortality Risk in Non-Hemodialyzed Chronic Kidney Disease: The Mediating Role of Plasma ACE Level.

The association between angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms and plasma ACE levels may allow for the optimization of a preventive intervention to reduce cardiovascular morbidity and mortality in the chronic kidney disease (CKD) population. In this study, we aimed to analyze the association between ACE I/D polymorphism and cardiovascular mortality risk among non-hemodialyzed chronic kidney disease patients. This cross-sectional study examined 70 patients of Javanese ethnic origin with stable CKD who did not receive hemodialysis. ACE I/D polymorphisms, plasma ACE levels, atherosclerotic cardiovascular disease (ASCVD) risk, and cardiovascular mortality risk were investigated. As per our findings, the I allele was found to be more frequent (78.6) than the D allele (21.4), and the DD genotype was less frequent than the II genotype (4.3 vs. 61.4). The ACE I/D polymorphism had a significant direct positive effect on plasma ACE levels (path coefficient = 0.302, p = 0.021). Similarly, plasma ACE levels had a direct and significant positive effect on the risk of atherosclerotic cardiovascular disease (path coefficient = 0.410, p = 0.000). Moreover, atherosclerotic cardiovascular disease risk had a significant positive effect on cardiovascular mortality risk (path coefficient = 0.918, p = 0.000). The ACE I/D polymorphism had no direct effect on ASCVD and cardiovascular mortality risk. However, our findings show that the indirect effects of high plasma ACE levels may be a factor in the increased risk of ASCVD and cardiovascular mortality in Javanese CKD patients.

The association of depression and central obesity on hypertension in Indonesian provinces: a path analysis of the Indonesian baseline health research 2018 data.

Purpose: This study aims to analyse the direct and indirect relationship between the prevalence of depression and hypertension through central obesity in the Indonesian population.Material and methods: This quantitative analytical observational study is based on secondary data with a cross-sectional design. The data is taken from the Indonesian Baseline Health Research of the Health Research and Development Agency in 2018, which is aggregated data from survey results on household members in 34 Indonesian provinces. We used path analysis and the Sobel test using AMOS 23.0 program to assess the direct and indirect relationship of depression and obesity to hypertension. Multiple linear regression analysis was used to determine the effect of confounding factors on hypertension.Results: The average prevalence (± SD) of depression, central obesity and hypertension in 2018 was 6.21% (± 2.30), 31.26% (± 4.80), and 31.07% (± 4.76). There was an indirect positive relationship between depression and hypertension through central obesity (p = 0.041). The direct effect of depression was associated with a 17% chance of being centrally obese (p = 0.009), and the direct effect of depression and central obesity was associated with a 32.7% chance of becoming hypertensive (p = 0.001). There is no significant direct relationship between depression and hypertension. The effect of confounding factors on hypertension was 21.9% (p = 0.007), lower than the effect of depression and central obesity.Conclusion: Central obesity might be an intermediate variable linking depression and hypertension.

The effect of statin administration on IL-6 and IL-1b expression in peripheral blood mononuclear cells of a hypertensive patient with SARS-CoV-2 spike protein stimulation.

Aim The infection of the SARS-CoV-2 virus potentially causes a cytokine storm with elevated IL-6 and IL-1ß levels. Statin therapy was common among COVID-19 patients due to their cardiovascular comorbidities. However, the effect of statins on COVID-19 infection is unclear. The aim of this study was to evaluate the impact of statin administration on IL-6 and IL-1ß level in peripheral blood mononuclear cells (PBMCs) after SARS-CoV-2 spike protein stimulation. Methods The PBMCs were isolated from a hypertensive patient and stimulated by the SARS-CoV-2 subunit S1 spike protein. The PBMCs were then divided into four treatment groups and treated with simvastatin at various doses (10 µM, 25 µM, 50 µM, and control). IL-6 and IL-1ß were measured from the supernatant using the ELISA method. Results The stimulation of SARS-CoV-2 spike protein in PBMC cell culture statistically increased IL-6 and IL1ß expression of 5.2 and 35.07 fold, respectively (p<0.05). The expressions of IL-6 and IL-1ß were not statistically significant among three simvastatin doses and control. Conclusion Statin administration did not have significant effect on IL-6 and IL-1ß levels in PBMCs after SARS-CoV-2 spike protein stimulation in this study, a further study is needed.

High Sensitivity Troponin T as Complementary Modality for Determining Doxorubicin Regimen Cardiotoxicity in Non-Hodgkin Lymphoma Patients.

Purpose: This study aims to evaluate the role of high-sensitivity troponin T (hsTnT) as a complementary tool for determining cardiotoxicity in non-Hodgkin lymphoma (NHL) patients receiving cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen chemotherapy. Methods: We included 35 patients diagnosed with NHL who received CHOP chemotherapy. Left ventricular ejection fraction (LVEF) and hsTnT were measured at two time points: before the first cycle (pre-test) and after the fourth cycle (post-test). The LVEF and hsTnT were analysed using IBM SPSS version 24 through the paired-sample T-test, Wilcoxon signed-rank test, Pearson's correlation and Spearman's correlation. Results: There was a significant difference in both LVEF and hsTnT between pre-chemotherapy and post-4th chemotherapy cycles (P = 0.001). However, more contrast difference from the baseline value of hsTnT compared to LVEF could be observed. LVEF did not detect any deterioration in myocardial function. However, 10 out of 35 subjects exhibit hsTnT higher than the 99th percentile of the population (>14 pg/ml), suggesting that myocardial injury (MI) could be detected. There was no correlation between LVEF and hsTnT (P > 0.05). Conclusion: HsTnT, together with LVEF, could complement each other and offer better coverage for detecting cardiotoxicity during the administration of CHOP in NHL patients. An insignificant correlation between hsTnT and LVEF showed that cardiotoxicity existed in a broad spectrum including cellular damage and functional impairment, as hsTnT represents cellular damage, and LVEF reflects heart functional capacity.

Efficiency Comparison of Direct Reprogramming CD34+ Cells into Cardiomyocytes Using Cardiomyocyte Differentiation Medium vs MicroRNA-1.

The development of a direct reprogramming method to provide cell availability for regenerative therapy has led to a lot of studies. However, the search for appropriate cell sources and methods is still being carried out until now. Direct reprogramming using microRNA-1 (miR-1) is an option to obtain cardiomyocytes from other cells because miR-1 has evidence to play a role in the development of cardiac muscle cells in the embryo. This study aimed to compare the direct reprogramming efficiency of CD34+ cells from peripheral blood into cardiomyocytes between cardiomyocyte differentiation medium and miR-1. CD34+ cells from peripheral blood isolation and expansion process was conducted for 7 days using magnetic-activated cell sorting. Cardiomyocyte differentiation medium added in P1 group and transfection of miR-1 in P2 group of cell culture. Cardiac troponin immunocytochemistry staining and measurement were done on the fifth day after cell culture treatment. Cardiac troponin expression was observed higher in the P2 group (median 31.34) compared to the P1 group (median 21.06) (p = 0.000). The efficiency of direct reprogramming of CD34+ cells into cardiomyocytes with cardiomyocyte differentiation medium was 13%-21% and with miR-1 transfection was 31%-32%. Both the addition of miR-1 and cardiomyocyte differentiation medium could directly reprogram CD34+ cells into cardiomyocytes. The efficiency of miR-1 in reprogramming CD34+ cells into cardiomyocytes is superior to cardiomyocytes differentiation medium.

Acute effects of cigarette smoke on Endothelial Nitric Oxide synthase, vascular cell adhesion molecule 1 and aortic intima media thickness.

Background. Cigarette smoking could induce endothelial dysfunction and the increase of circulating markers of inflammation by activation of monocytes. This can lead to increased intima media thickness (IMT) of entire blood vessels and result in acceleration of the atherosclerosis process. However, to our knowledge, little is known about the role of cigarette smoking in this atherosclerotic inflammatory process. The aim of this study is to explore the link between cigarette smoking and its effect on endothelial nitric oxide synthase (e-NOS) and vascular cell adhesion molecule 1 (VCAM-1). Methods. An experimental study with a post-test only controlled group design was used. We used 18 Wistar rats ( Rattus norvegicus) randomly subdivided into two groups: group K (-) were not exposed to tobacco smoke, whereas group K (+) were exposed to smoke equivalent of more than 40 cigarettes for 28 days daily. After 28 days, samples were analyzed for e-NOS, VCAM-1 and aortic IMT. Results . Our results indicate that tobacco smoke can enhance the expression of VCAM-1 on rat cardiac vascular endothelial cells, resulting in a decreased expression of e-NOS level and increase of aortic IMT. Linear regression model found that eNOS level negatively correlated wiith aortic IMT ( r 2 = 0.584, ß = -0.764, p < 0.001), whereas VCAM-1 expression did not correlate with aortic IMT ( r 2 = 0.197, p = 0.065). Conclusion. Low e-NOS level and high VCAM-1 level observed after cigarette smoke exposure which may increase aortic IMT.

Correlation between anti-hypertensive drugs and disease progression among moderate, severe, and critically ill COVID-19 patients in the second referral hospital in Surabaya: A retrospective cohort study.

Background: Hypertension, as the comorbidity accompanying COVID-19, is related to angiotensin-converting enzyme 2 receptor (ACE-2R) and endothelial dysregulation which have an important role in blood pressure regulation. Other anti-hypertensive agents are believed to trigger the hyperinflammation process. We aimed to figure out the association between the use of anti-hypertensive drugs and the disease progression of COVID-19 patients.   Methods: This study is an observational cohort study among COVID-19 adult patients from moderate to critically ill admitted to Universitas Airlangga Hospital (UAH) Surabaya with history of hypertension and receiving anti-hypertensive drugs.   Results: Patients receiving beta blockers only had a longer length of stay than angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ACEI/ARB) or calcium channel blockers alone (17, 13.36, and 13.73 respectively), had the higher rate of intensive care unit (ICU) admission than ACEi/ARB (p 0.04), and had the highest mortality rate (54.55%). There were no significant differences in length of stay, ICU admission, mortality rate, and days of death among the single, double, and triple anti-hypertensive groups. The mortality rate in groups taking ACEi/ARB was lower than other combination.   Conclusions: Hypertension can increase the severity of COVID-19. The use of ACEI/ARBs in ACE-2 receptor regulation which is thought to aggravate the condition of COVID-19 patients has not yet been proven. This is consistent with findings in other anti-hypertensive groups.