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BACKGROUND@#Innovative coronavirus disease 2019 (COVID-19) vaccines, with elevated global manufacturing capacity, enhanced safety and efficacy, simplified dosing regimens, and distribution that is less cold chain-dependent, are still global imperatives for tackling the ongoing pandemic. A previous phase I trial indicated that the recombinant COVID-19 vaccine (V-01), which contains a fusion protein (IFN-PADRE-RBD-Fc dimer) as its antigen, is safe and well tolerated, capable of inducing rapid and robust immune responses, and warranted further testing in additional clinical trials. Herein, we aimed to assess the immunogenicity and safety of V-01, providing rationales of appropriate dose regimen for further efficacy study.@*METHODS@#A randomized, double-blind, placebo-controlled phase II clinical trial was initiated at the Gaozhou Municipal Centre for Disease Control and Prevention (Guangdong, China) in March 2021. Both younger (n = 440; 18-59 years of age) and older (n = 440; ≥60 years of age) adult participants in this trial were sequentially recruited into two distinct groups: two-dose regimen group in which participants were randomized either to follow a 10 or 25 μg of V-01 or placebo given intramuscularly 21 days apart (allocation ratio, 3:3:1, n = 120, 120, 40 for each regimen, respectively), or one-dose regimen groups in which participants were randomized either to receive a single injection of 50 μg of V-01 or placebo (allocation ratio, 3:1, n = 120, 40, respectively). The primary immunogenicity endpoints were the geometric mean titers of neutralizing antibodies against live severe acute respiratory syndrome coronavirus 2, and specific binding antibodies to the receptor binding domain (RBD). The primary safety endpoint evaluation was the frequencies and percentages of overall adverse events (AEs) within 30 days after full immunization.@*RESULTS@#V-01 provoked substantial immune responses in the two-dose group, achieving encouragingly high titers of neutralizing antibody and anti-RBD immunoglobulin, which peaked at day 35 (161.9 [95% confidence interval [CI]: 133.3-196.7] and 149.3 [95%CI: 123.9-179.9] in 10 and 25 μg V-01 group of younger adults, respectively; 111.6 [95%CI: 89.6-139.1] and 111.1 [95%CI: 89.2-138.4] in 10 and 25 μg V-01 group of older adults, respectively), and remained high at day 49 after a day-21 second dose; these levels significantly exceed those in convalescent serum from symptomatic COVID-19 patients (53.6, 95%CI: 31.3-91.7). Our preliminary data show that V-01 is safe and well tolerated, with reactogenicity predominantly being absent or mild in severity and only one vaccine-related grade 3 or worse AE being observed within 30 days. The older adult participants demonstrated a more favorable safety profile compared with those in the younger adult group: with AEs percentages of 19.2%, 25.8%, 17.5% in older adults vs. 34.2%, 23.3%, 26.7% in younger adults at the 10, 25 μg V-01 two-dose group, and 50 μg V-01 one-dose group, respectively.@*CONCLUSIONS@#The vaccine candidate V-01 appears to be safe and immunogenic. The preliminary findings support the advancement of the two-dose, 10 μg V-01 regimen to a phase III trial for a large-scale population-based evaluation of safety and efficacy.@*TRIAL REGISTRATION@#http://www.chictr.org.cn/index.aspx (No. ChiCTR2100045107, http://www.chictr.org.cn/showproj.aspx?proj=124702).
Subject(s)
Aged , Humans , Antibodies, Viral , COVID-19/therapy , COVID-19 Vaccines , Double-Blind Method , Immunization, Passive , Recombinant Fusion Proteins , SARS-CoV-2ABSTRACT
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a kind of inherited cardio-myopathy, which is characterized by fibro-fatty replacement of right ventricular myocardium, leading to ventricular arrhythmia. However, rapid atrial arrhythmias are also common, including atrial fibrillation, atrial flutter and atrial tachycardia. Long term rapid atrial arrhythmia can lead to further deterioration of cardiac function. This case is a 51-year-old male. He was admitted to Department of Cardiology, Peking University Third Hospital with palpitation and fatigue after exercise. Electrocardiogram showed incessant atrial tachycardia. Echocardiography revealed dilation of all his four chambers, especially the right ventricle, with the left ventricular ejection fraction of 40% and the right ventricular hypokinesis. Cardiac magnetic resonance imaging found that the right ventricle was significantly enlarged, and the right ventricular aneurysm had formed; the right ventricular ejection fraction was as low as 8%, and the left ventricular ejection fraction was 35%. The patients met the diagnostic criteria of ARVC, and both left and right ventricles were involved. His physical activities were restricted, and metoprolol, digoxin, spironolactone and ramipril were given. Rivaroxaban was also given because atrial tachycardia could cause left atrial thrombosis and embolism. His atrial tachycardia converted spontaneously to normal sinus rhythm after these treatments. Since the patient had severe right ventricular dysfunction, frequent premature ventricular beats and non-sustained ventricular tachycardia on Holter monitoring, indicating a high risk of sudden death, implantable cardioverter defibrillator (ICD) was implanted. After discharge from hospital, physical activity restriction and the above medicines were continued. As rapid atrial arrhythmia could lead to inappropriate ICD shocks, amiodarone was added to prevent the recurrence of atrial tachycardia, and also control ventricular arrhythmia. After 6 months, echocardiography was repeated and showed that the left ventricle diameter was reduced significantly, and the left ventricular ejection fraction increased to 60%, while the size of right ventricle and right atrium decreased slightly. According to the clinical manifestations and outcomes, he was diagnosed with ARVC associated with arrhythmia induced cardiomyopathy. According to the results of his cardiac magnetic resonance imaging, the patient had left ventricular involvement caused by ARVC, and the persistent atrial tachycardia led to left ventricular systolic dysfunction.
Subject(s)
Humans , Male , Middle Aged , Arrhythmogenic Right Ventricular Dysplasia/complications , Atrial Fibrillation , Stroke Volume , Ventricular Function, Left , Ventricular Function, RightABSTRACT
BACKGROUND@#Angiopoietin-2 (Ang-2) is a type of endothelial growth factor involved in angiogenesis and vascular remodeling. Circulating Ang-2 levels are elevated in patients with obstructive coronary artery disease (CAD). This study aimed to evaluate the association between serum Ang-2 levels and coronary microvascular dysfunction in patients without obstructive CAD.@*METHODS@#A total of 125 patients with angina in the absence of obstructive CAD were included in this cross-sectional study. Coronary flow reserve (CFR) was measured in the distal left anterior descending coronary artery by trans-thoracic Doppler echocardiography. The patients were divided into the following two sub-groups according to CFR: the impaired CFR group with CFR values <2.5 and the preserved CFR group with CFR values ≥2.5. Serum Ang-2 levels were determined using enzyme-linked immunosorbent assay. Independent predictors for impaired CFR were identified by binary logistic regression analysis. The receiver-operating characteristic curve was determined to evaluate the ability of serum Ang-2 in predicting impaired CFR.@*RESULTS@#We found that age, percentage of female sex, N-terminal pro-B-type natriuretic peptide levels, Ang-2 levels (763.3 ± 264.9 vs. 579.7 ± 169.3 pg/mL, P < 0.001), and the left atrial volume index were significantly higher in patients with impaired CFR than in patients with preserved CFR. Serum Ang-2 levels were negatively correlated with CFR (r = -0.386, P < 0.001). Binary logistic regression analysis showed that Ang-2 (odds ratio: 1.004, 95% confidence interval [CI]: 1.001-1.006, P = 0.003) and age (odds ratio: 1.088, 95% CI: 1.023-1.156, P = 0.007) were independently associated with impaired CFR. Furthermore, Ang-2 was a significant predictor of impaired CFR on the receiver-operating characteristic curve (P < 0.001). The area under the curve was 0.712 (95% CI: 0.612-0.813).@*CONCLUSIONS@#High serum Ang-2 levels are independently associated with impaired CFR in patients with angina in the absence of obstructive CAD.
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Objective To investigate 5-year survival after ST-segment elevation myocardial infarction(STEMI)in Beijing Yanqing district. Methods A total of 691 STEMI patients admitted to Beijing Yanqing hospital from August 2002 to December 2010 were followed up for as long as 5 years. The end point was all cause death. Five-year survival curve was computed for patients who had received primary percutaneous coronary intervention(pPCI)and patients who had not received pPCI. Predictors of death within 5 years were identified by multivariable cox regression analysis. Results In 691 patient,442 patients(64.0％)had not received pPCI,and 249 patients(36.0％)had received pPCI. The 5-year survival rates were 73.8％ and 93.6％in patients who had not received pPCI and patients who had received pPCI separately. The predictors of death within 5 years in patients who had not received pPCI were female,age,chronic obstructive pulmonary disease, Killip's class ≥ 2 in hospital,myocardial infarction of anterior wall and not receiving elective PCI,while the predictors in patients who had received pPCI were age and gastrointestinal bleeding. Conclusions The 5-year survival rate in patients who had received pPCI was obviously higher than in patients who had not received pPCI. The predictors of death within 5 years were different in the two groups.
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<p><b>OBJECTIVE</b>To explore the current status of morning blood pressure and medication of hypertensive patients in Beijing.</p><p><b>METHODS</b>This study included 2187 hypertensive patients who visited the ambulance of our cardiology department in the morning (7:00-10:00) from March 2012 to April 2012. Patients were divided into three groups: no antihypertensive agent group, single antihypertensive drug therapy group (include CCB, ARB, ACEI, β-blocker) and combined drug therapy group at least one month. Blood pressure control rate was compared among the groups.</p><p><b>RESULTS</b>Target blood pressure was not reached in 1193 patients (54.6%), most patients took CCB and the target blood pressure was not reached in 61.7% (295/478) patients taking CCB. There was no significant difference on target blood pressure uncontrolled rate among the four single drug subgroups (CCB, ARB, ACEI, β-blocker). The blood pressure uncontrolled rate was 46.3% (63/136) for amlodipine, 70.5% (55/78) for nifedipine and 73.8% (31/42) for felodipine. There OR of uncontrolled blood pressure rate was 0.36 (amlodipine vs. nifedipine, 95%CI:0.20-0.65) and 0.31% (amlodipine vs. felodipine, 95%CI:0.14-0.66).</p><p><b>CONCLUSION</b>The morning blood pressure uncontrolled rate is high in hypertensive patients visiting Beijing tertiary hospitals. Amlodipine is possible superior to nifedipine and felodipine on morning blood pressure control in this patient cohort.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Blood Pressure , Hypertension , Drug Therapy , Time FactorsABSTRACT
<p><b>OBJECTIVE</b>To evaluate the effect of a phospholipid-coated microbubble contrast agent for myocardium opacification in comparison with a albumin-coated microbubble contrast agent (Quanfuxian).</p><p><b>METHODS</b>In 10 dogs with single coronary artery stenosis involving the anterior descending branch or circumflex branch randomly received infusion of the two contrast agents through the femoral vein. The myocardial blood flow, heart rate and blood pressure were analyzed qualitatively and quantitatively. The concentration and the particle diameter of the two contrast agents were determined.</p><p><b>RESULTS</b>The concentration of the phospholipid-coated microbubbles was (1.06-/+0.22) x10(9)/ml, with a diameter of 3.04-/+0.34 microm, similar to the concentration and diameter of Quanfuxian ((1.31-/+0.33)x10(9)/ml and 2.88-/+0.58 microm, respectively, P>0.05). Both of the agents achieved grade three myocardium opacification, and produced no obvious effect on the heart rate and blood pressure. Quantitative analysis of myocardial opacification in terms of myocardial blood volume (A), blood velocity (beta), and blood flow (A x beta) revealed no significant difference between the two agents (P>0.05), and the parameters derived from the two agents showed good correlations (P<0.05, rA=0.809, r beta=0.932, rA.beta=0.925).</p><p><b>CONCLUSION</b>The phospholipid-coated microbubble contrast agent shows good effect for myocardial opacification without significant difference from Quanfuxian. Both of the agents are good ultrasound contrast agents for quantitative analysis of myocardium blood flow.</p>
Subject(s)
Animals , Dogs , Female , Male , Albumins , Chemistry , Contrast Media , Chemistry , Coronary Stenosis , Diagnostic Imaging , Echocardiography , Methods , Microbubbles , Phospholipids , ChemistryABSTRACT
<p><b>OBJECTIVE</b>To compare the therapeutic effect of recombinant human brain natriuretic peptide (rhBNP) and nitroglycerin on acute decompensated heart failure (ADHF).</p><p><b>METHODS</b>Fifty ADHF patients were randomly divided into rhBNP group and nitroglycerin group. In all the patients, dyspnea and global clinical status were assessed before and at 30 min, 6 h and 24 h after drug administration, and the volume of fluid intake and urine along with hemodynamic parameters was recorded 24 h after drug administration. In the nitroglycerin group, the patients received an initial nitroglycerin dose of 5 microg/min, with subsequent dose increment of 5 microg/min every 3 to 5 min; the dose was adjusted individually according to the hemodynamics of the patients. The patients in rhBNP group were given rhBNP at the initial dose of 1.5 microg/kg by with an intravenous bolus injection followed by infusion at the rate of 0.0075 microg.kg(-1).min(-1) for 72 h.</p><p><b>RESULTS</b>At 30 min and 6 h after drug administration, the patients in the rhBNP group showed significant greater improvement of dyspnea (P=0.042 and 0.019) and global clinical status (P=0.018 and 0.044) than those in the nitroglycerin group, but 24 h after drug administration, no significant difference was noted between the two groups (P=0.192 and 0.179). Twenty-four hours after drug administration, the mean urine volume was significantly greater in rhBNP group than in nitroglycerin group (1513.8-/+242.9 vs 1341.2-/+239.7 ml, P=0.015), and the ejection fraction increased and pulmonary arterial pressure and systolic blood pressure decreased at greater amplitude in the former group (P=0.001,0.000 and 0.002, respectively). At 72 h, the numbers of premature ventricular contraction and couplets premature beats and onset of paroxysmal ventricular tachycardia were significantly reduced in rhBNP group as compared with the nitroglycerin group (P=0, 0.001 and 0.002, respectively).</p><p><b>CONCLUSION</b>RhBNP promotes urine excretion, decreases pulmonary arterial pressure and increases left ventricular ejection fraction to improve dyspnea and global clinical status and reduce the onset of ventricular arrhythmia in ADHF patients.</p>
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Blood Pressure , Heart Failure , Drug Therapy , Pathology , Infusions, Intravenous , Natriuretic Peptide, Brain , Genetics , Therapeutic Uses , Nitric Oxide Donors , Therapeutic Uses , Nitroglycerin , Therapeutic Uses , Recombinant Proteins , Therapeutic Uses , Treatment OutcomeABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of nitroglycerine (NTG) on myocardial oxygen metabolism and regional cardiac function in canine hearts with a stable systemic hemodynamics in situ.</p><p><b>METHODS</b>Eight anesthetized open-chest dogs with flow-limited left anterior descending branch of the coronary artery or left circumflex artery (LCx) stenosis were studied. The percentage of ventricular wall thickening (%WT) was measured with quantitative two-dimensional echocardiography (2DE), myocardial blood flow (MBF) with radiolabeled microspheres and tissue oxygen pressure (tPO(2).) with oxygen-dependent quenching of phosphorescence. 2DE was performed and radiolabeled microspheres and Pd-porphyrin injected in the dogs at rest during intracoronary infusion of 0.3-0.6 mg x kg(-1) x min(-1) of NTG. Myocardial oxygen consumption (MVO(2), ml x min(-1) x 100 g(-1)) was calculated as the multiplication product between the arterio-venous oxygen content difference and MBF, and myocardial O(2) delivery as the product between arterial oxygen content and MBF.</p><p><b>RESULTS</b>As compared with the baseline, NTG increased %WT and MBF significantly in both normal and ischemic beds (P<0.05). There was a significant increase in MVO(2) during NTG infusion in the ischemic bed (P<0.05) in comparison with that measured at rest. NTG, however, significantly increased the ability of myocardial O(2) delivery in both normal and ischemic beds (P<0.05), therefore tPO(2) was still higher in the ischemic bed during NTG infusion than that at rest (P<0.05). The percentage increment in tPO(2) was significantly greater in the ischemic bed than percentage MBF increment.</p><p><b>CONCLUSIONS</b>NTG enhances myocardial oxygen concentration in normal and ischemic myocardium and may increase oxygen release to the ischemic myocardium in vivo. NTG may have a positive inotropic effect on regional cardiac function. In addition to direct effect on vascular tone, NTG plays important roles in the cardiovascular system by modulating myocardial oxygen metabolism and contractile function.</p>