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Background

The optimal noninvasive test (NIT) for patients with diabetes and stable symptoms of coronary artery disease (CAD) is unknown.

Objectives

The purpose of this study was to assess whether a diagnostic strategy based on coronary computed tomographic angiography (CTA) is superior to functional stress testing in reducing adverse cardiovascular (CV) outcomes (CV death or myocardial infarction [MI]) among symptomatic patients with diabetes.

Methods

PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) was a randomized trial evaluating an initial strategy of CTA versus functional testing in stable outpatients with symptoms suggestive of CAD. The study compared CV outcomes in patients with diabetes (n = 1,908 [21%]) and without diabetes (n = 7,058 [79%]) based on their randomization to CTA or functional testing.

Results

Patients with diabetes (vs. without) were similar in age (median 61 years vs. 60 years) and sex (female 54% vs. 52%) but had a greater burden of CV comorbidities. Patients with diabetes who underwent CTA had a lower risk of CV death/MI compared with functional stress testing (CTA: 1.1% [10 of 936] vs. stress testing: 2.6% [25 of 972]; adjusted hazard ratio: 0.38; 95% confidence interval: 0.18 to 0.79; p = 0.01). There was no significant difference in nondiabetic patients (CTA: 1.4% [50 of 3,564] vs. stress testing: 1.3% [45 of 3,494]; adjusted hazard ratio: 1.03; 95% confidence interval: 0.69 to 1.54; p = 0.887; interaction term for diabetes p value = 0.02).

Conclusions

In diabetic patients presenting with stable chest pain, a CTA strategy resulted in fewer adverse CV outcomes than a functional testing strategy. CTA may be considered as the initial diagnostic strategy in this subgroup. (PROspective Multicenter Imaging Study for Evaluation of Chest Pain [PROMISE]; NCT01174550)  相似文献   
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In May 2017, the Health and Environmental Sciences Institute's Genetic Toxicology Technical Committee hosted a workshop to discuss whether mode of action (MOA) investigation is enhanced through the application of the adverse outcome pathway (AOP) framework. As AOPs are a relatively new approach in genetic toxicology, this report describes how AOPs could be harnessed to advance MOA analysis of genotoxicity pathways using five example case studies. Each of these genetic toxicology AOPs proposed for further development includes the relevant molecular initiating events, key events, and adverse outcomes (AOs), identification and/or further development of the appropriate assays to link an agent to these events, and discussion regarding the biological plausibility of the proposed AOP. A key difference between these proposed genetic toxicology AOPs versus traditional AOPs is that the AO is a genetic toxicology endpoint of potential significance in risk characterization, in contrast to an adverse state of an organism or a population. The first two detailed case studies describe provisional AOPs for aurora kinase inhibition and tubulin binding, leading to the common AO of aneuploidy. The remaining three case studies highlight provisional AOPs that lead to chromosome breakage or mutation via indirect DNA interaction (inhibition of topoisomerase II, production of cellular reactive oxygen species, and inhibition of DNA synthesis). These case studies serve as starting points for genotoxicity AOPs that could ultimately be published and utilized by the broader toxicology community and illustrate the practical considerations and evidence required to formalize such AOPs so that they may be applied to genetic toxicity evaluation schemes. Environ. Mol. Mutagen. 61:114–134, 2020. © 2019 Wiley Periodicals, Inc.  相似文献   
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Abstract Background: Does there exist a difference in the outcome of severely injured children and severely injured healthy adults? Methods: The data of 1,566 severely injured patients, treated between May 1998 and December 2002 in our emergency department of the University Essen/Germany, were analyzed. Patients with an injury severity score (ISS) > 24 were included in the present study. Patients younger as 18 (17) years were located to the children group c. Patients aged 18 and up to the age of 54 were included in the adult group a. Results: Fifty-four children and 252 adults met the selection criteria. ISS and the Glasgow coma scale (GCS) before intubation were not statistically different in both groups. Seriously injured children stayed significantly shorter on the intensive care unit, required significantly less ventilator days. Furthermore, the incidence of single organ failure (SOF) and multiple organ failure (MOF) was significantly lower in the children group. Mortality in the children group (29.6%) was lower than that in the adult group (33.7%). There was no death due to MOF in the children group as compared to 2.4% (n = 6) in the adults. Conclusion: The incidence of SOF and MOF was significantly lower in the children group although there was no difference in ISS, GCS and injury patterns. The prognosis of severely injured children was found to be better than those of adults. Moreover, there was no death due to MOF in the children group.  相似文献   
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Oxygen-sensitive F-19 magnetic resonance imaging of perfluorocarbon compounds requires that fluorocarbon T1 changes correlate with the local Po2 and not with the composition of the surrounding aqueous phase. The influence of various bioconstituents and paramagnetic ions within the aqueous phase on the F-19 fluorocarbon phase T1 for PFC emulsions was evaluated at 0.14 and 0.66 T. T1 was measured for FC-43, perflubron, and a fluorinated surfactant. Controlled variables introduced in the aqueous phase included annex solution constituents, blood, pH changes, and Gd-DTPA. For a constant Po2, the F-19 T1s were independent of the emulsion constituents, blood concentration, and pH. For FC-43 and perflubron, F-19 T1 was independent of the Gd-DTPA concentration, while the aqueous phase T1 decreased by more than an order of magnitude. XMO-10 (smallest emulsion particle size) showed a slight decrease in F-19 T1 with increasing Gd-DTPA concentration at 0.66 T.  相似文献   
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3-(Methylnitrosamino)propionitrile (MNPN), a potent carcinogen in F344 rats, was detected for the first time in the saliva of betel quid chewers at levels ranging from 0.5 to 11.4 micrograms/liter. The tumorigenic properties of MNPN and its potential to methylate DNA in F344 rats were evaluated. Groups of 21 male and 21 female rats were given 60 s.c. injections over a 20-week period (total doses 0.055 and 0.23 mmol per rat). The experiment was terminated after 106 weeks. MNPN at the higher dose induced 18 (86%) malignant tumors of the nasal cavity in male and 15 (71%) in female rats. The lower dose induced nine (43%) liver tumors. Groups of four or five male F344 rats were treated with a single s.c. or i.v. injection of MNPN (0.4 mmol/kg). MNPN was also administered to rats by swabbing the oral cavity (2.21 mmol/kg). The levels of 7-methylguanine and O6-methylguanine, formed 0.5-36 h after treatment, were measured in the liver, nasal mucosa, esophagus, and oral issues. The highest levels of methylated guanines were detected in the nasal cavity independent of the route of administration. The results of this study demonstrate that MNPN is present in the saliva of betel quid chewers and is a potent carcinogen in F344 rats.  相似文献   
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BACKGROUND: Despite different available methods for colorectal cancer (CRC) screening and their proven benefits, morbidity, and mortality of this malignancy are still high, partly due to low compliance with screening. Minimally invasive tests based on the analysis of blood specimens may overcome this problem. The purpose of this review was to give an overview of published studies on blood markers aimed at the early detection of CRC and to summarize their performance characteristics. METHOD: The PUBMED database was searched for relevant studies published until June 2006. Only studies with more than 20 cases and more than 20 controls were included. Information on the markers under study, on the underlying study populations, and on performance characteristics was extracted. Special attention was given to performance characteristics by tumor stage. RESULTS: Overall, 93 studies evaluating 70 different markers were included. Most studies were done on protein markers, but DNA markers and RNA markers were also investigated. Performance characteristics varied widely between different markers, but also between different studies using the same marker. Promising results were reported for some novel assays, e.g., assays based on SELDI-TOF MS or MALDI-TOF MS, for some proteins (e.g., soluble CD26 and bone sialoprotein) and also for some genetic assays (e.g., L6 mRNA), but evidence thus far is restricted to single studies with limited sample size and without further external validation. CONCLUSIONS: Larger prospective studies using study populations representing a screening population are needed to verify promising results. In addition, future studies should pay increased attention to the potential of detecting precursor lesions.  相似文献   
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