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  • 1
    Publication Date: 2016-08-25
    Description: Background Contrast-induced acute kidney injury (CI-AKI) is typically defined by an increase in serum creatinine after intravascular administration of contrast medium. Because creatinine is an unreliable indicator of acute changes in kidney function, we assessed whether circulating microRNAs (miRNAs) could serve as biomarkers for early detection of CI-AKI. Methods and Results Using a rat model of CI-AKI, we first evaluated the miRNA profile of rat plasma and kidney. Three miRNA species with 〉1.5-fold increase in plasma samples of CI-AKI rats, including miRNA-188, miRNA-30a, and miRNA-30e, were selected as candidate miRNAs. Quantitative real-time polymerase chain reaction showed that these candidate miRNAs peaked in concentration around 4 hours after contrast medium exposure and were relatively renal-specific. We compared the plasma levels of these candidate miRNAs in 71 patients who underwent coronary angiography or percutaneous coronary intervention and developed CI-AKI with those of 71 matched controls. The plasma levels of the 3 candidate miRNAs were significantly elevated in the CI-AKI group as compared to the control group. Receiver operating characteristic analysis showed that these miRNAs significantly distinguished patients with CI-AKI from those without CI-AKI. MiRNA composites were highly accurate for CI-AKI prediction, as shown in maximized specificity by treble-positive miRNA composite or maximized Youden index by any-positive miRNA composite. Moreover, the selected miRNAs changes were associated with Mehran Risk Scores. Conclusions Plasma levels of candidate miRNAs significantly distinguished patients with CI-AKI from those without CI-AKI. Thus, miRNAs are potential biomarkers for early detection of CI-AKI.
    Keywords: Biomarkers
    Electronic ISSN: 2047-9980
    Topics: Medicine
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  • 2
    Publication Date: 2012-09-25
    Description: Background and Purpose— We explored the association between pulsatility index (PI) as derived from transcranial Doppler ultrasound with various measures of small vessel disease in the community. Methods— We performed transcranial Doppler and magnetic resonance imaging in 205 consecutive community-dwelling elderly subjects who were participants of the Shanghai Aging Study. We investigated the association between middle cerebral artery (MCA) PI with measures of white matter lesions (WML), lacunes, and microbleeds. Results— Multiple logistic regression found that MCA PI was associated with severe WML (odds ratio, 1.33 per 0.1 increase in PI; 95% confidence interval, 1.04–1.70; P =0.02). At optimal MCA PI cut-off, the area under curve, positive predictive value, and negative predictive value were 0.70 (95% confidence interval, 0.60–0.80), 34.9%, and 85.6%, respectively, for detection of severe WML. No association was found between MCA PI and measures of lacunes or microbleeds. Conclusions— PI correlates with WML severity. With a high negative predictive value, the chance of having severe WML with a normal PI is low. Transcranial Doppler may guide selective magnetic resonance imaging scanning for the detection of WML in the community.
    Keywords: Doppler ultrasound, Transcranial Doppler etc., Primary and Secondary Stroke Prevention
    Print ISSN: 0039-2499
    Electronic ISSN: 1524-4628
    Topics: Medicine
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  • 3
    Publication Date: 2013-01-17
    Description: Primary hypertension is a chronic disease with high morbidity, and the rate of controlled blood pressure is far from satisfactory, worldwide. Vaccination provides a promising approach for treatment of hypertension and improvement in compliance. Here, the ATRQβ-001 vaccine, a peptide (ATR-001) derived from human angiotensin II (Ang II) receptor type 1 conjugated with Qβ bacteriophage virus-like particles, was developed and evaluated in animal models of hypertension. The ATRQβ-001 vaccine significantly decreased the blood pressure of Ang II–induced hypertensive mice up to 35 mm Hg (143±4 versus 178±6 mm Hg; P =0.005) and that of spontaneously hypertensive rats up to 19 mm Hg (173±2 versus 192±3 mm Hg; P =0.003) and prevented remodeling of vulnerable hypertensive target organs. No obvious feedback activation of circulating or local renin-angiotensin system was observed. Additionally, no significant immune-mediated damage was detected in vaccinated hypertensive and nonhypertensive animals. The half-life of the anti-ATR-001 antibody was 14.4 days, surpassing that of existing chemical drugs. In vitro, the anti–ATR-001 antibody specifically bound to Ang II receptor type 1 and inhibited Ca 2+ -dependent signal transduction events, including protein kinase C-α translocation, extracellular signal-regulated kinase 1/2 phosphorylation (72% decrease; P =0.013), and elevation of intracellular Ca 2+ (68% decrease; P =0.017) induced by Ang II, but without inhibiting Ang II binding to the receptor. In conclusion, the ATRQβ-001 vaccine decreased the blood pressure of Ang II–induced hypertensive mice and spontaneously hypertensive rats effectively through diminishing the pressure response and inhibiting signal transduction initiated by Ang II. Thus, the ATRQβ-001 vaccine may provide a novel and promising method for the treatment of primary hypertension.
    Print ISSN: 0194-911X
    Topics: Medicine
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  • 4
    Publication Date: 2016-01-26
    Description: Background and Purpose— The benefit of intervention for patients with unruptured cerebral arteriovenous malformations (AVMs) was challenged by results demonstrating superior clinical outcomes with conservative management from A Randomized Trial of Unruptured Brain AVMs (ARUBA). The aim of this multicenter, retrospective cohort study is to analyze the outcomes of stereotactic radiosurgery for ARUBA-eligible patients. Methods— We combined AVM radiosurgery outcome data from 7 institutions participating in the International Gamma Knife Research Foundation. Patients with ≥12 months of follow-up were screened for ARUBA eligibility criteria. Favorable outcome was defined as AVM obliteration, no postradiosurgery hemorrhage, and no permanently symptomatic radiation–induced changes. Adverse neurological outcome was defined as any new or worsening neurological symptoms or death. Results— The ARUBA-eligible cohort comprised 509 patients (mean age, 40 years). The Spetzler–Martin grade was I to II in 46% and III to IV in 54%. The mean radiosurgical margin dose was 22 Gy and follow-up was 86 months. AVM obliteration was achieved in 75%. The postradiosurgery hemorrhage rate during the latency period was 0.9% per year. Symptomatic and permanent radiation–induced changes occurred in 11% and 3%, respectively. The rates of favorable outcome, adverse neurological outcome, permanent neurological morbidity, and mortality were 70%, 13%, 5%, and 4%, respectively. Conclusions— Radiosurgery may provide durable clinical benefit in some ARUBA-eligible patients. On the basis of the natural history of untreated, unruptured AVMs in the medical arm of ARUBA, we estimate that a follow-up duration of 15 to 20 years is necessary to realize a potential benefit of radiosurgical intervention for conservative management in unruptured patients with AVM.
    Keywords: Cerebral Aneurysm, Cerebrovascular Disease/Stroke, Cerebrovascular Malformations, Cerebrovascular Procedures, Intracranial Hemorrhage
    Print ISSN: 0039-2499
    Electronic ISSN: 1524-4628
    Topics: Medicine
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  • 5
    Publication Date: 2015-12-24
    Description: Background Chinese form a large proportion of the immigrant population in Western countries. There is evidence that Chinese immigrants experience an increased risk of coronary heart disease (CHD) after immigration in part due to cultural habits and acculturation. This is the first systematic review and meta-analysis that aims to examine the risk of CHD in people of Chinese ethnicity living in Western countries, in comparison with whites and another major immigrant group, South Asians. Methods and Results Literature on the incidence, mortality, and prognosis of CHD among Chinese living in Western countries was searched systematically in any language using 6 electronic databases up to December 2014. Based on the meta-analysis, Chinese had lower incidence of CHD compared with whites (odds ratio 0.29; 95% CI: 0.24–0.34) and South Asians (odds ratio 0.37; 95% CI: 0.24–0.57) but higher short-term mortality after first hospitalization for acute myocardial infarction compared with whites (odds ratio 1.34; 95% CI, 1.04–1.73) and South Asians (odds ratio 1.82; 95% 1.33–2.50). There was no significant difference between Chinese immigrants and whites in long-term outcomes (mortality and recurrent events) after acute myocardial infarction. Conclusions These findings provide an important focus for resource planning to enhance early secondary prevention of CHD to improve short-term survival outcomes among Western-dwelling Chinese immigrants.
    Electronic ISSN: 2047-9980
    Topics: Medicine
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