The use of multiplex PCR for the diagnosis of viral severe acute respiratory infection in children: a high rate of co-detection during the winter season.

Respiratory tract infection is a major cause of hospitalization in children. Although most such infections are viral in origin, it is difficult to differentiate bacterial and viral infections, as the clinical symptoms are similar. Multiplex polymerase chain reaction (PCR) methods allow testing for multiple pathogens simultaneously and are, therefore, gaining interest. This prospective case-control study was conducted from October 2013 to February 2014. Nasopharyngeal (NP) and oropharyngeal (throat) swabs were obtained from children admitted with severe acute respiratory infection (SARI) at a tertiary hospital. A control group of 40 asymptomatic children was included. Testing for 16 viruses was done by real-time multiplex PCR. Multiplex PCR detected a viral pathogen in 159/177 (89.9 %) patients admitted with SARI. There was a high rate of co-infection (46.9 %). Dual detections were observed in 64 (36.2 %), triple detections in 17 (9.6 %), and quadruple detections in 2 (1.1 %) of 177 samples. Seventy-eight patients required intensive care unit (ICU) admission, of whom 28 (35.8 %) had co-infection with multiple viruses. AdV, HBoV, HRV, HEV, and HCoV-OC43 were also detected among asymptomatic children. This study confirms the high rate of detection of viral nucleic acids by multiplex PCR among hospitalized children admitted with SARI, as well as the high rate of co-detection of multiple viruses. AdV, HBoV, HRV, HEV, and HCoV-OC43 were also detected in asymptomatic children, resulting in challenges in clinical interpretation. Studies are required to provide quantitative conclusions that will facilitate clinical interpretation and application of the results in the clinical setting.

Helicobacter pylori Infection: Clinical, Endoscopic, and Histological Findings in Lebanese Pediatric Patients.

BACKGROUND: Helicobacter pylori (H. pylori) is a common and universally distributed bacterial infection. However, in children, active gastritis and ulcer are rarely seen. OBJECTIVES: The aims of this study were to establish the prevalence of H. pylori infection and to compare the clinical, endoscopic, and histopathological findings between infected and noninfected pediatric patients at Makassed General Hospital. METHODS: Patients aged between 1 month and 17 years who underwent upper gastrointestinal endoscopy from January 2011 to January 2017 were included. The diagnosis of H. pylori was confirmed by a CLO test and/or its presence on biopsy specimens. Demographic data, clinical characteristics, endoscopic and histopathological findings, and gastritis score were recorded retrospectively. RESULTS: During the study period, 651 children underwent upper gastrointestinal endoscopy. The main indication was abdominal pain (61%). The prevalence of H. pylori infection was 16.5%. The infection was most commonly seen among children aged between 6 and 10 years (43%). A large number of family members were associated with increased risk of infection (4.8 ± 1.5 versus 5.2 ± 1.8; p < 0.05). Epigastric pain was more associated with H. pylori (61.3% versus 14.6% in noninfected patients; p < 0.05). Nodular gastritis was commonly seen in infected patients (41.5% vs. 7.9%; p < 0.05). Mild and moderate gastritis was seen more in infected versus noninfected patients (mild: 53.8% vs. 14%; moderate: 27.4% vs. 2.4%, respectively). CONCLUSION: Although epigastric pain was associated with H. pylori, other diagnoses should be considered since the infection are rarely symptomatic in children. Antral nodularity was associated with H. pylori infection; however, its absence does not preclude the diagnosis.

Ultrasound-triggered delivery of paclitaxel encapsulated in an emulsion at low acoustic pressures.

We investigated the in vitro ultrasound-triggered delivery of paclitaxel, a well known anti-cancerous drug, encapsulated in an emulsion and in the presence of CT26 tumor cells. The emulsion was made of nanodroplets, whose volume comprised 95% perfluoro-octyl bromide and 5% tributyl O-acetylcitrate, in which paclitaxel was solubilized. These nanodroplets, prepared using a high-pressure microfluidizer, were stabilized by a tailor-made and recently patented biocompatible fluorinated surfactant. The delivery investigations were performed at 37 °C using a high intensity focused ultrasound transducer at a frequency of 1.1 MHz. The ultrasonic pulse was made of 275 sinusoidal periods and the pulse repetition frequency was 200 Hz with a duty cycle of 5%. The measured viabilities of CT26 cells showed that paclitaxel delivery was achievable for peak-to-peak pressures of 0.4 and 3.5 MPa, without having to vaporize the perfluorocarbon part of the droplet or to induce inertial cavitation.

Plasma inflammatory cytokines and survival of pancreatic cancer patients.

OBJECTIVES: Inflammation and inflammatory conditions have been associated with pancreatic cancer risk and progression in a number of clinical, epidemiological, and animal model studies. The goal of the present study is to identify plasma markers of inflammation associated with survival of pancreatic cancer patients, and assess their joint contribution to patient outcome. METHODS: We measured circulating levels of four established markers of inflammation (C-reactive protein (CRP), interleukin-6 (IL-6), soluble tumor necrosis factor receptor type II (sTNF-RII), and macrophage inhibitory cytokine-1 (MIC-1)) in 446 patients enrolled in an ongoing prospective clinic-based study. Hazard ratios (HRs) and 95% confidence intervals (CI) for death were estimated using multivariate Cox proportional hazards models. RESULTS: Overall mortality was significantly increased in patients in the top quartile of CRP (HR = 2.52, 95% CI: 1.82-3.49), IL-6 (HR = 2.78, 95% CI: 2.03-3.81), sTNF-RII (HR = 2.00, 95% CI: 1.46-2.72), and MIC-1 (HR = 2.53, 95% CI: 1.83-3.50), compared to those in the bottom quartile (P-trend <0.0001 for all four comparisons). Furthermore, patients with higher circulating concentrations of all four cytokines had a median survival of 3.7 months; whereas, those with lower levels had a median survival of 19.2 months (HR = 4.55, 95% CI: 2.87-7.20, P-trend <0.0001). CONCLUSION: Individual elevated plasma inflammatory cytokines are associated with significant and dramatic reductions in pancreatic cancer patient survival. Furthermore, we observed an independent combined effect of those cytokines on patient survival, suggesting that multiple inflammatory pathways are likely involved in PDAC progression. Future research efforts to target the inflammatory state using combination strategies in pancreatic cancer patients are warranted.

Effects of testosterone therapy on cardiovascular risk markers in androgen-deficient women with hypopituitarism.

CONTEXT: Low-dose testosterone replacement therapy in women with relative androgen deficiency has been shown to have beneficial effects on body composition, bone mass, and psychosexual function. However, the safety of chronic testosterone administration on cardiovascular risk and insulin resistance is unknown. OBJECTIVE: The aim of the study was to determine the effects of physiological testosterone replacement on cardiovascular risk markers and insulin resistance in women. DESIGN: A 12-month, randomized, placebo-controlled study was conducted. SETTING: A General Clinical Research Center was the setting for the study. STUDY PARTICIPANTS: A total of 51 women of reproductive age with androgen deficiency due to hypopituitarism participated. INTERVENTION: Study participants were randomized to physiological testosterone administration, 300 mug daily, or placebo, by patch. MAIN OUTCOME MEASURES: We measured fasting glucose, fasting insulin, insulin-resistance homeostasis model of assessment (IRHOMA), quantitative insulin sensitivity check index (QUICKI), high-sensitivity C-reactive protein, vascular cell adhesion molecule (VCAM), leptin, lipoprotein (a), apolipoprotein A1, and homocysteine. RESULTS: At 12 months, fasting insulin and IRHOMA were significantly lower in the testosterone compared with the placebo group, and there was a trend toward a higher QUICKI level at 12 months in the testosterone compared with the placebo group. These differences were no longer significant after controlling for baseline levels. We observed no effect, either positive or negative, of testosterone administration on high-sensitivity C-reactive protein, VCAM leptin, lipoprotein (a), or apolipoprotein A1. CONCLUSIONS: Our data suggest that physiological testosterone replacement in women with hypopituitarism for 12 months does not increase, and may improve, insulin resistance. Chronic low-dose testosterone administration does not increase markers of cardiovascular disease reflecting several different mechanistic pathways. Large, randomized, placebo-controlled, long-term prospective studies are needed to determine whether low-dose testosterone replacement affects cardiovascular risk and event rates in women.

Therapy with oral clotrimazole induces inhibition of the Gardos channel and reduction of erythrocyte dehydration in patients with sickle cell disease.

Pathologic water loss from sickle erythrocytes concentrates the abnormal hemoglobin and promotes sickling. The Ca2+-activated K+ channel (Gardos channel) contributes to this deleterious dehydration in vitro, and blockade of K+ and water loss via this channel could be a potential therapy in vivo. We treated five subjects who have sickle cell anemia with oral clotrimazole, a specific Gardos channel inhibitor. Patients were started on a dose of 10 mg clotrimazole/kg/d for one week. Protocol design allowed the daily dose to be escalated by 10 mg/kg each week until significant changes in erythrocyte density and K+ transport were achieved. Blood was sampled three times a week for hematological and chemical assays, erythrocyte density, cation content, and K+ transport. At dosages of 20 mg clotrimazole/kg/d, all subjects showed Gardos channel inhibition, reduced erythrocyte dehydration, increased cell K+ content, and somewhat increased hemoglobin levels. Adverse effects were limited to mild/moderate dysuria in all subjects, and a reversible increase in plasma alanine transaminase and aspartic transaminase levels in two subjects treated with 30 mg clotrimazole/kg/d. This is the first in vivo evidence that the Gardos channel causes dehydration of sickle erythrocytes, and that its pharmacologic inhibition provides a realistic antisickling strategy.

Use of cardiac troponin T levels as an indicator of doxorubicin-induced cardiotoxicity.

The release of cardiac troponin T (cTnT) as a biomarker of doxorubicin-induced chronic cardiac injury was evaluated in the spontaneously hypertensive rat (SHR) model. Elevations in serum levels of cTnT and decreased immunohistochemical staining of heart sections for this protein were noted in SHRs treated with cumulative doses of doxorubicin (7 mg/kg) that induced only minimal histological alterations in myocytes. Concentrations of cTnT were further elevated, coincident with reduced immunohistochemical staining, in SHRs given 10-12 mg/kg doxorubicin. Thus, monitoring serum levels of cTnT can detect doxorubicin-induced myocyte damage in SHR and may prove useful for the noninvasive evaluation of this toxicity in humans.

Towards microfluidic reactors for in situ synchrotron infrared studies.

Anodically bonded etched silicon microfluidic devices that allow infrared spectroscopic measurement of solutions are reported. These extend spatially well-resolved in situ infrared measurement to higher temperatures and pressures than previously reported, making them useful for effectively time-resolved measurement of realistic catalytic processes. A data processing technique necessary for the mitigation of interference fringes caused by multiple reflections of the probe beam is also described.

Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia.

BACKGROUND: Long-term therapy with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) has been shown to reduce levels of C-reactive protein (CRP). However, the generalizability, speed of onset, and dose-response characteristics of this effect are uncertain. METHODS AND RESULTS: We measured CRP, LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) levels among 785 patients with primary hypercholesterolemia at baseline and after 8 weeks of therapy with either 0.4 or 0.8 mg of cerivastatin. Overall, cerivastatin resulted in a 13.3% reduction in median CRP levels (P:<0.001) and a 24.5% reduction in mean CRP levels (P:<0.001). Although LDL-C promptly decreased in a dose-dependent manner (mean LDL-C reduction, 37.3% for 0.4 mg and 42.2% for 0.8 mg of cerivastatin), no clear dose-response effect of cerivastatin on CRP was observed, nor was there any substantive correlation between the magnitude of change in CRP and the magnitude of change in LDL-C (r=-0.08) or the magnitude of change in HDL-C (r=-0.04). Thus, <2% of the variance in the percent change in CRP over 8 weeks could be attributed to the percent change in either of these lipid parameters. Further, there was no evidence of correlation between baseline CRP levels and baseline lipid levels or between end-of-study CRP levels and end-of-study lipid levels. CONCLUSIONS: Among 785 patients with primary hypercholesterolemia, CRP levels were significantly reduced within 8 weeks of initiating cerivastatin therapy in a lipid-independent manner.

Soluble P-selectin and the risk of future cardiovascular events.

BACKGROUND: P-selectin, a cell-surface adhesion molecule involved in leukocyte rolling and attachment, has been hypothesized to play a role in the initiation of atherosclerosis. However, little clinical data are available evaluating the role of soluble P-selectin in determining vascular risk. METHODS AND RESULTS: In a large-scale prospective study of apparently healthy women, we measured baseline plasma concentration of soluble P-selectin among 115 participants who subsequently developed cardiovascular events and among 230 age- and smoking-matched participants who remained free of disease during 3.5 years of follow-up. Overall, mean levels of soluble P-selectin were significantly higher at baseline among women who subsequently experienced cardiovascular events compared with those who did not (83.2 versus 69.3 ng/mL; P:=0.003). The risk of future cardiovascular events increased with increasing quartiles of soluble P-selectin (P:=0.02), such that women in the highest quartile at study entry had an age- and smoking-matched relative risk 2.2 times higher than those in the lowest quartile (95% confidence interval, 1.2 to 4.2; P:=0.01). This effect was independent of traditional risk factors. For each quartile increase in soluble P-selectin, the risk of future cardiovascular events increased 28% (P:=0.03) after additional adjustment for obesity, hypertension, hyperlipidemia, diabetes, and exercise frequency. The highest risks were observed among women with the very highest levels of P-selectin (>137.3 ng/mL, the 95th percentile cut point of the control distribution). CONCLUSIONS: Soluble P-selectin levels are elevated among apparently healthy women at risk for future vascular events.

Long-term effects of pravastatin on plasma concentration of C-reactive protein. The Cholesterol and Recurrent Events (CARE) Investigators.

BACKGROUND: Elevated plasma concentrations of C-reactive protein (CRP) are associated with increased cardiovascular risk. We evaluated whether long-term therapy with pravastatin, an agent that reduces cardiovascular risk, might alter levels of this inflammatory parameter. METHODS AND RESULTS: CRP levels were measured at baseline and at 5 years in 472 randomly selected participants in the Cholesterol and Recurrent Events (CARE) trial who remained free of recurrent coronary events during follow-up. Overall, CRP levels at baseline and at 5 years were highly correlated (r=0.60, P<0.001). However, among those allocated to placebo, median CRP levels and the mean change in CRP tended to increase over time (median change, +4. 2%; P=0.2 and mean change, +0.07 mg/dL; P=0.04). By contrast, median CRP levels and the mean change in CRP decreased over time among those allocated to pravastatin (median change, -17.4%; P=0.004 and mean change, -0.07 mg/dL; P=0.002). Thus, statistically significant differences were observed at 5 years between the pravastatin and placebo groups in terms of median CRP levels (difference, -21.6%; P=0.007), mean CRP levels (difference, -37.8%; P=0.002), and absolute mean change in CRP (difference, -0.137 mg/dL; P=0.003). These effects persisted in analyses stratified by age, body mass index, smoking status, blood pressure, and baseline lipid levels. Attempts to relate the magnitude of change in CRP to the magnitude of change in lipids in both the pravastatin and placebo groups did not reveal any obvious relationships. CONCLUSIONS: Among survivors of myocardial infarction on standard therapy plus placebo, CRP levels tended to increase over 5 years of follow-up. In contrast, randomization to pravastatin resulted in significant reductions in this inflammatory marker that were not related to the magnitude of lipid alterations observed. Thus, these data further support the potential for nonlipid effects of this agent.

Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men.

BACKGROUND: Interleukin-6 (IL-6) plays a central role in inflammation and tissue injury. However, epidemiological data evaluating the role of IL-6 in atherogenesis are sparse. METHODS AND RESULTS: In a prospective study involving 14 916 apparently healthy men, we measured baseline plasma concentration of IL-6 in 202 participants who subsequently developed myocardial infarction (MI) and in 202 study participants matched for age and smoking status who did not report vascular disease during a 6-year follow-up. Median concentrations of IL-6 at baseline were higher among men who subsequently had an MI than among those who did not (1.81 versus 1. 46 pg/mL; P=0.002). The risk of future MI increased with increasing quartiles of baseline IL-6 concentration (P for trend <0.001) such that men in the highest quartile at entry had a relative risk 2.3 times higher than those in the lowest quartile (95% CI 1.3 to 4.3, P=0.005); for each quartile increase in IL-6, there was a 38% increase in risk (P=0.001).This relationship remained significant after adjustment for other cardiovascular risk factors, was stable over long periods of follow-up, and was present in all low-risk subgroups, including nonsmokers. Although the strongest correlate of IL-6 in these data was C-reactive protein (r=0.43, P<0.001), the relationship of IL-6 with subsequent risk remained after control for this factor (P<0.001). CONCLUSIONS: In apparently healthy men, elevated levels of IL-6 are associated with increased risk of future MI. These data thus support a role for cytokine-mediated inflammation in the early stages of atherogenesis.

Hormone replacement therapy and increased plasma concentration of C-reactive protein.

BACKGROUND: It has been hypothesized that postmenopausal hormone replacement therapy (HRT) may increase levels of C-reactive protein (CRP), a marker of inflammation associated with increased risk of future cardiovascular events. However, data evaluating this hypothesis are sparse and limited to older women. METHODS AND RESULTS: CRP levels were evaluated in a cross-sectional survey of 493 healthy postmenopausal women; mean age was 51 years. Overall, median CRP levels were 2 times higher among women taking HRT than among women not taking HRT (0.27 versus 0.14 mg/dL; P=0.001). This difference was present in all subgroups evaluated, including those with no history of hypertension, hyperlipidemia, obesity, diabetes, or cigarette consumption or a family history of premature coronary artery disease (all P< 0.01). Compared with nonusers of HRT, median CRP levels were higher among women using estrogen alone (P=0.003) and women using estrogen plus progesterone (P=0.03); however, there was no significant difference in CRP levels between users of different HRT preparations. In multivariate analysis, the relationship between HRT use and CRP remained significant after control for body mass index, age, diabetes, hypertension, hyperlipidemia, alcohol use, and cigarette consumption (P=0.001). CONCLUSIONS: In this cross-sectional survey, CRP levels were increased among apparently healthy postmenopausal women taking HRT. The potential impact of HRT on inflammatory parameters should be investigated in ongoing clinical trials.

Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction.

BACKGROUND: Levels of tumor necrosis factor-alpha (TNF-alpha) increase with acute ischemia. However, whether elevations of TNF-alpha in the stable phase after myocardial ischemia (MI) are associated with increased risk of recurrent coronary events is unknown. METHODS AND RESULTS: A nested case-control design was used to compare TNF-alpha levels obtained an average of 8.9 months after initial MI among 272 participants in the Cholesterol And Recurrent Events (CARE) trial who subsequently developed recurrent nonfatal MI or a fatal cardiovascular event (cases) and from an equal number of age- and sex-matched participants who remained free of these events during follow-up (controls). Overall, TNF-alpha levels were significantly higher among cases than controls (2.84 versus 2.57 pg/mL, P=0.02). The excess risk of recurrent coronary events after MI was predominantly seen among those with the highest levels of TNF-alpha, such that those with levels in excess of 4.17 pg/mL (the 95th percentile of the control distribution) had an approximately 3-fold increase in risk (RR=2.7, 95% CI 1.4 to 5.2, P=0.004). Risk estimates were independent of other risk factors and were similar in subgroup analyses limited to cardiovascular death (RR=2.1) or to recurrent nonfatal MI (RR=3.2). CONCLUSIONS: Plasma concentrations of TNF-alpha are persistently elevated among post-MI patients at increased risk for recurrent coronary events. These data support the hypothesis that a persistent inflammatory instability is present among stable patients at increased vascular risk. Novel therapies designed to attenuate inflammation may thus represent a new direction in the treatment of MI.

Truncal adiposity, relative growth hormone deficiency, and cardiovascular risk.

We hypothesized that endogenous GH would be reduced in healthy women with relative truncal adiposity despite lack of generalized obesity and that decreased GH would be associated with increased cardiovascular risk markers. Fifteen healthy female volunteers were divided into two groups, low truncal fat and high truncal fat, of comparable body mass index (BMI). Age and BMI (23.7 +/- 2.1 vs. 25.8 +/- 2.8 kg/m(2)) were similar in the two groups. Trunk fat was higher in the high-truncal-fat group, as designed. Twenty-four-hour mean GH, amplitude, and basal GH concentration were 41, 32, and 36% lower, respectively, in the high-truncal-fat group, but GH pulse frequency and IGF-I levels did not differ. In a stepwise regression model, trunk fat accounted for 38% of the variation of mean GH levels (P = 0.02), but neither total body fat nor BMI were significant determinants of mean GH in the model. There was a strong inverse association between mean 24-h GH and both truncal fat and cardiovascular risk markers, including high-sensitivity C-reactive protein. Our data suggest that visceral adiposity may be associated with reduced endogenous GH in healthy women, even in the absence of generalized obesity, and that decreased GH secretion may be associated with increased cardiovascular risk markers in this population.

Correlation between serum levels of cardiac troponin-T and the severity of the chronic cardiomyopathy induced by doxorubicin.

PURPOSE: To investigate, over a wide range of cumulative doxorubicin doses, the feasibility of using serum concentrations of cardiac troponin-T (cTnT) as a biomarker for doxorubicin-induced myocardial damage. MATERIALS AND METHODS: Groups of spontaneously hypertensive rats (SHR) were given 1 mg/kg doxorubicin weekly for 2 to 12 weeks. Cardiomyopathy scores were assessed according to the method of Billingham and serum levels of cTnT were quantified by a noncompetitive immunoassay. Myocardial localization of cTnT was studied by immunohistochemical staining and confocal microscopy. RESULTS: Increases in serum levels of cTnT (0.03 to 0.05 ng/mL) and myocardial lesions (cardiomyopathy scores of 1 or 1.5) were found in one out of five and two out of five SHR given 2 and 4 mg/kg doxorubicin, respectively. All animals given 6 mg/kg or more of doxorubicin had increases in serum cTnT and myocardial lesions. The average cTnT levels and the cardiomyopathy scores correlated with the cumulative dose of doxorubicin (0.13 v 0.4 ng/mL cTnT and scores of 1.4 v 3.0 in SHR given 6 and 12 mg/kg doxorubicin, respectively). Decreased staining for cTnT was observed in cardiac tissue from SHR receiving cumulative doses that caused only minimal histologic alterations (scores of 1 to 1.5). Staining for cTnT decreased simultaneously with increases in the severity of the cardiomyopathy scores. CONCLUSION: cTnT is released from doxorubicin-damaged myocytes. Measurements of serum levels of this protein seem to provide a sensitive means for assessing the early cardiotoxicity of doxorubicin.

Lack of association of C-reactive protein and coronary calcium by electron beam computed tomography in postmenopausal women: implications for coronary artery disease screening.

OBJECTIVES: We sought to test the hypothesis that C-reactive protein, a marker of inflammation, would correlate positively with coronary calcium, a marker of atherosclerosis, in postmenopausal women. BACKGROUND: High sensitivity testing for C-reactive protein (hsCRP) has recently been shown in large population studies to predict cardiac events in asymptomatic postmenopausal women. Coronary calcification determined by electron beam computerized tomography (EBCT) has also been suggested to be predictive of cardiac events in women. METHODS: We performed hsCRP testing and determined calcium scores by EBCT in 172 asymptomatic postmenopausal women (mean age: 64.5 +/- 7.9 years) at risk for cardiac disease. Risk factors were determined by history, physical, electrocardiogram, exercise testing, and lipoprotein profiles. RESULTS: Calcium scores ranged from 0 to 2,618. For analysis, calcium scores were divided into three groups; none (0 to 10), minimal (>10 to 50), and significant (>50). Overall, there was no significant positive relationship between hsCRP level and calcium score. Specifically, the hsCRP levels (mg/dl) were 0.24 +/- 0.43, 0.33 +/- 0.47 and 0.17 +/- 0.32 (medians 0.11, 0.15, and 0.06) for women with none, minimal, and significant coronary calcification, respectively. In subgroup analysis, a similar lack of positive association was observed after stratification by smoking status and by hormone replacement therapy use, two factors known to increase hsCRP. CONCLUSIONS: In contrast to our a priori hypothesis, we found no evidence of a positive association between hsCRP and calcium score by EBCT. These data thus raise the possibility that hsCRP and EBCT calcium score reflect different pathologic processes, an issue with implications for coronary artery disease screening.

Time to positivity of a rapid bedside assay for cardiac-specific troponin T predicts prognosis in acute coronary syndromes: a Thrombolysis in Myocardial Infarction (TIMI) 11A substudy.

OBJECTIVES: We sought to determine whether the rapid bedside assay for troponin T identified patients at risk for a more complicated hospital stay and a higher rate of adverse clinical events. BACKGROUND: In patients with an acute coronary syndrome, the amount of cardiac-specific troponin T released bears a stoichiometric relation to the extent of myocardial damage. METHODS: In 597 patients with unstable angina or non-Q wave myocardial infarction participating in the Thrombolysis in Myocardial Infarction (TIMI) 11A substudy, a rapid bedside assay and simultaneous quantitative serum measurement for troponin T were obtained at enrollment. RESULTS: The composite end point of the sum of death, nonfatal myocardial infarction or recurrent ischemia through day 14 occurred in 33.6% of patients with a positive assay compared with only 22.5% of patients with a negative assay (p = 0.01). Those patients in whom the rapid assay became positive in < or = 10 min had the highest mortality rate of 4.2% through day 14 compared with 1.1% in those patients who had either a late-appearing positive assay (> 10 min) or a negative assay. The duration of hospital stay in the 116 patients (19%) with a positive rapid assay at enrollment was a median of 5 days compared with only 3 days in the 481 patients (81%) with a negative rapid assay at enrollment (p = 0.002). CONCLUSIONS: A positive rapid assay for troponin T at presentation identifies those patients at risk for higher rates of adverse clinical events and longer, more complicated hospital stays. Stratification of patients by time to development of a positive rapid assay identifies those patients at highest mortality risk.

Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI-11B substudy.

OBJECTIVES: We sought to evaluate cardiac troponin I (cTnI) for predicting early clinical outcomes and the efficacy of enoxaparin among patients with non-ST segment elevation acute coronary syndrome (ACS) and negative creatine kinase, MB fraction (CK-MB) levels. BACKGROUND: Cardiac TnI identifies patients with unstable angina who are at higher risk of death or myocardial infarction (MI) by 30 days. The utility of cTnI for predicting very early clinical events, including recurrent ischemia, and the efficacy of enoxaparin are not yet established. METHODS: At baseline and 12 h to 24 h after enrollment in the Thrombolysis in Myocardial Infarction (TIMI)-11B trial, samples were collected for cTnI determination. RESULTS: Among 359 patients with negative serial CK-MB values, 50.1% had a cTnI result > or =0.1 ng/ml within the first 24 h. Patients with elevated cTnI were at higher risk of death or MI at 48 h (3.9 vs. 0%, p = 0.01) and 14 days (13.9 vs. 2.2%, p<0.0001). Elevated cTnI also correlated with higher risk of recurrent ischemia requiring urgent revascularization by 48 h (10.0 vs. 1.7%, p = 0.001) and 14 days (20.6 vs. 5.6%, p< or =0.0001). Enoxaparin had a greater benefit among patients with elevated vs. normal cTnI (p = 0.03), achieving a 47% reduction in the risk of death, MI or urgent revascularization by 14 days in cTnI-positive patients (p = 0.007). CONCLUSIONS: Elevation of cTnI among patients with non-ST segment elevation ACS and negative levels of CK-MB identifies those at higher risk for very early adverse outcomes, including severe recurrent ischemia. Treatment with enoxaparin reduces the risk associated with elevated cTnI.