Search Results : biomarker

May 232013
 
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Plasma angiopoietin-2 predicts the onset of acute lung injury in critically ill patients.

Am J Respir Crit Care Med. 2013 Apr 1;187(7):736-42

Authors: Agrawal A, Matthay MA, Kangelaris KN, Stein J, Chu JC, Imp BM, Cortez A, Abbott J, Liu KD, Calfee CS

Abstract
RATIONALE: Current clinical prediction scores for acute lung injury (ALI) have limited positive predictive value. No studies have evaluated predictive plasma biomarkers in a broad population of critically ill patients or as an adjunct to clinical prediction scores.
OBJECTIVES: To determine whether plasma angiopoietin-2 (Ang-2), von Willebrand factor (vWF), interleukin-8 (IL-8), and/or receptor for advanced glycation end products (sRAGE) predict ALI in critically ill patients.
METHODS: Plasma samples were drawn from critically ill patients (n = 230) identified in the emergency department. Patients who had ALI at baseline or in the subsequent 6 hours were excluded, and the remaining patients were followed for development of ALI.
MEASUREMENTS AND MAIN RESULTS: Nineteen patients developed ALI at least 6 hours after the sample draw. Higher levels of Ang-2 and IL-8 were significantly associated with increased development of ALI (P = 0.0008, 0.004, respectively). The association between Ang-2 and subsequent development of ALI was robust to adjustment for sepsis and vasopressor use. Ang-2 and the Lung Injury Prediction Score each independently discriminated well between those who developed ALI and those who did not (area under the receiver operating characteristic curve, 0.74 for each), and using the two together improved the area under the curve to 0.84 (vs. 0.74, P = 0.05). In contrast, plasma levels of sRAGE and vWF were not predictive of ALI.
CONCLUSIONS: Plasma biomarkers such as Ang-2 can improve clinical prediction scores and identify patients at high risk for ALI. In addition, the early rise of Ang-2 emphasizes the importance of endothelial injury in the early pathogenesis of ALI.

PMID: 23328529 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

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May 222013
 

Yield of Routine Provocative Cardiac Testing Among Patients in an Emergency Department-Based Chest Pain Unit: Yield of Stress Testing in Emergency Department Observation Units.

JAMA Intern Med. 2013 May 20;:1-6

Authors: Hermann LK, Newman DH, Pleasant WA, Rojanasarntikul D, Lakoff D, Goldberg SA, Duvall WL, Henzlova MJ

Abstract
IMPORTANCE The American Heart Association recommends routine provocative cardiac testing in accelerated diagnostic protocols for coronary ischemia. The diagnostic and therapeutic yield of this approach are unknown. OBJECTIVE To assess the yield of routine provocative cardiac testing in an emergency department-based chest pain unit. DESIGN AND SETTING We examined a prospectively collected database of patients evaluated for possible acute coronary syndrome between March 4, 2004, and May 15, 2010, in the emergency department-based chest pain unit of an urban academic tertiary care center. PARTICIPANTS Patients with signs or symptoms of possible acute coronary syndrome and without an ischemic electrocardiography result or a positive biomarker were enrolled in the database. EXPOSURES All patients were evaluated by exercise stress testing or myocardial perfusion imaging. MAIN OUTCOMES AND MEASURES Demographic and clinical features, results of routine provocative cardiac testing and angiography, and therapeutic interventions were recorded. Diagnostic yield (true-positive rate) was calculated, and the potential therapeutic yield of invasive therapy was assessed through blinded, structured medical record review using American Heart Association designations (class I, IIa, IIb, or lower) for the potential benefit from percutaneous intervention. RESULTS In total, 4181 patients were enrolled in the study. Chest pain was initially reported in 93.5%, most (73.2%) were at intermediate risk for coronary artery disease, and 37.6% were male. Routine provocative cardiac testing was positive for coronary ischemia in 470 (11.2%), of whom 123 underwent coronary angiography. Obstructive disease was confirmed in 63 of 123 (51.2% true positive), and 28 (0.7% overall) had findings consistent with the potential benefit from revascularization (American Heart Association class I or IIa). CONCLUSIONS AND RELEVANCE In an emergency department-based chest pain unit, routine provocative cardiac testing generated a small therapeutic yield, new diagnoses of coronary artery disease were uncommon, and false-positive results were common.

PMID: 23689690 [PubMed - as supplied by publisher]

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May 212013
 

Cardiac Troponin after Percutaneous Coronary Intervention and 1-Year Mortality in NSTE ACS Using Systematic Evaluation of Biomarker Trends.

J Am Coll Cardiol. 2013 May 15;

Authors: Tricoci P, Leonardi S, White J, White HD, Armstrong PW, Montalescot G, Giugliano RP, Gibson CM, Van de Werf F, Califf RM, Harrington RA, Braunwald E, Mahaffey KW, Newby LK

Abstract
OBJECTIVES: We reviewed cardiac troponin (cTn) trends during non-ST-segment elevation acute coronary syndrome (NSTE ACS) in patients undergoing percutaneous coronary intervention (PCI) in EARLY ACS and SYNERGY and studied the relationship between post-PCI cTn and mortality. BACKGROUND: The prognostic value of cTn post-PCI is controversial. In patients with NSTE ACS, it is especially difficult to distinguish between cTn elevations due to PCI or index myocardial infarction (MI). METHODS: Time and cTn (indexed by upper limit of normal [ULN]) data pairs were plotted for 10,199 patients and independently reviewed by 2 physicians to identify patients in whom post-PCI cTn elevation could be distinguished from that of index MI. Post-PCI cTn peak was identified for each plot, and its relationship with 1-year mortality was evaluated using Cox modeling, correcting for 15 clinical variables from the EARLY ACS 1-year mortality model (including baseline cTn). We used an identical methodology to assess the association between creatine kinase-MB (CK-MB) and 1-year mortality. RESULTS: Patients with cTn (re)elevation post-PCI not evaluable were identified and excluded from further analysis (4198 [41%] with cTn rising prior to PCI; 229 [2%] with missing cTn). Among the remainder (N=5772 [57%]), in the multivariable model, peak cTn post-PCI was associated with a 7% increase in mortality (hazard ratio [HR] for 10x ULN increase, 1.07; 95% confidence interval [CI], 1.02-1.11; p=0.0038). Peak post-PCI CK-MB was significantly associated with 1-year mortality (HR for 1x ULN increase, 1.13; 95% CI, 1.05-1.21; p=0.0013). CONCLUSIONS: We used a methodology that differentiated post-PCI cTn (re)elevation from that of presenting MI in more than half of patients with NSTE ACS undergoing PCI. This identified a highly significant relationship between post-PCI cTn and 1-year mortality, with implication for both incorporating a cTn post-PCI MI definition and preventing PCI-related myonecrosis.

PMID: 23684676 [PubMed - as supplied by publisher]

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May 152013
 
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Management of candidaemia and invasive candidiasis in critically ill patients.

Int J Antimicrob Agents. 2013 May 8;

Authors: Chahoud J, Kanafani ZA, Kanj SS

Abstract
Critically ill patients in the intensive care unit (ICU) are at increased risk of encountering bloodstream infections (BSIs) with Candida spp., associated with an elevated crude mortality rate. This supports the significance of early detection of infection and identification of the most effective management approach. A review of the various antifungal treatments and an evaluation of the diverse management approaches for invasive candidiasis in critically ill patients is necessary for guiding evidence-based decision-making. Different early detection schemes for invasive candidiasis are well documented in the literature. Other than the common use of blood cultures, new methods entail the use of risk prediction scores and biomarker tests. Regarding management strategies, different options are currently supported. These include prophylaxis, empirical therapy, pre-emptive therapy, and treatment of culture-documented infections. The choice of treatment is greatly dependent on several factors related to the patient and/or to the surrounding environment. Attention needs to be given to previous exposure to azoles, epidemiological data on dominant Candida spp. in local ICUs, severity of illness and associated morbidities. This paper summarises the most recent literature as well as the guidelines issued by the Infectious Diseases Society of America. The objective is to identify the best diagnosis and management approaches for serious Candida infections in critically ill patients. In addition, this article addresses an important aspect associated with managing candidaemia in critically ill patients pertaining to the decision for intravenous catheter removal.

PMID: 23664579 [PubMed - as supplied by publisher]

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May 112013
 
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Bias in associations of emerging biomarkers with cardiovascular disease.

JAMA Intern Med. 2013 Apr 22;173(8):664-71

Authors: Tzoulaki I, Siontis KC, Evangelou E, Ioannidis JP

Abstract
IMPORTANCE Numerous cardiovascular biomarkers are proposed as potential predictors of cardiovascular risk. OBJECTIVE To evaluate whether there is evidence for biases favoring statistically significant results and inflating associations in this literature. DESIGN AND SETTING PubMed search for meta-analyses of cardiovascular biomarkers that are not part of the Framingham Risk Score. MAIN OUTCOME MEASURES We estimated summary effects and between-study heterogeneity (considered "very large" for I2 > 75%). We evaluated whether large studies had significantly more conservative results than smaller studies (small-study effects) and whether there were too many studies with statistically significant results compared with what would be expected on the basis of the findings of the largest study in each meta-analysis. RESULTS Of 56 eligible meta-analyses, 49 had statistically significant results. Very large heterogeneity and small-study effects were seen in 9 and 13 meta-analyses, respectively. In 29 meta-analyses (52%), there was a significant excess of studies with statistically significant results. Only 13 of the statistically significant meta-analyses had more than 1000 cases and no hints of large heterogeneity, small-study effects, or excess significance. These included the associations of glomerular filtration rate and albumin to creatinine ratio in general and high-risk populations with cardiovascular disease mortality and of non-high-density lipoprotein cholesterol, serum albumin, Chlamydia pneumoniae IgG, glycosylated hemoglobin, nonfasting insulin, apolipoprotein B/AI ratio, erythrocyte sedimentation rate, and lipoprotein-associated phospholipase mass or activity with coronary heart disease. CONCLUSIONS AND RELEVANCE Selective reporting biases may be common in the evidence on emerging cardiovascular biomarkers. Most of the proposed associations of these biomarkers may be inflated.

PMID: 23529078 [PubMed - in process]

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May 082013
 
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Novel cardiovascular biomarkers in unexplained syncopal attacks: the SYSTEMA cohort.

J Intern Med. 2013 Apr;273(4):359-67

Authors: Fedorowski A, Burri P, Struck J, Juul-Möller S, Melander O

Abstract
OBJECTIVES: The aim of the study was to investigate the resting levels of novel cardiovascular biomarkers in common types of noncardiac syncope.
DESIGN AND SETTING: An observational study was conducted including 255 patients (mean age 60 years, range 15-93; 45% men) with unexplained syncopal attacks. Subjects underwent an expanded head-up tilt test including carotid sinus massage, and nitroglycerin provocation if indicated. Using logistic regression, we explored the associations between specific diagnoses of syncope and resting levels of circulating biomarkers: C-terminal pro-arginine vasopressin (CT-proAVP), C-terminal endothelin-1 precursor fragment (CT-proET-1), midregional fragments of pro-atrial natriuretic peptide (MR-proANP) and pro-adrenomedullin (MR-proADM).
RESULTS: A total of 142 (56%) patients were diagnosed with vasovagal syncope (VVS), 85 (33%) with orthostatic hypotension (OH) and 47 (18%) with carotid sinus hypersensitivity (CSH); in addition, 74 (29%) patients had more than one diagnosis. Thirty-five patients (14%) demonstrated a cardioinhibitory reflex. The probability of VVS was highest in the first quartile of MR-proANP [Q1 vs. Q4: odds ratio (OR) 5.57, 95% confidence interval (CI) 1.86-16.74; P < 0.001] and CT-proET-1 (OR 7.17, 95% CI 2.43-21.13; P < 0.001). By contrast, the probability of OH was highest in the fourth quartile of CT-proET-1 (Q4 vs. Q1: OR 8.66, 95% CI 2.49-30.17; P < 0.001). Furthermore, CSH was most frequently observed in the first quartile of MR-proANP (Q1 vs. Q4: OR 6.57, 95% CI 1.62-26.62; P = 0.008) among those over 60 years of age, whereas the cardioinhibitory reflex was strongly associated with low CT-proET-1 levels (Q1 vs. Q4: OR 69.7, 95% CI 6.97-696.6; P < 0.001). Moreover, in patients with VVS, a high concentration of CT-proET-1 was predictive of OH (OR per 1 SD 2.4, 95% CI 1.15-5.02; P = 0.02), whereas low CT-proET-1 suggested involvement of the cardioinhibitory reflex (OR per 1SD 0.42, 95% CI 0.25-0.70; P = 0.001).
CONCLUSIONS: The levels of MR-proANP and CT-proET-1 are markedly changed in common forms of syncope, suggesting the involvement of novel neurohormonal mechanisms in syncopal attacks.

PMID: 23510366 [PubMed - indexed for MEDLINE]

Link to Article at PubMed

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