Haemodynamic changes in emergency department patients with poorly controlled hypertension.

OBJECTIVES: This study aimed to measure cardiac output, systemic vascular resistance, cardiac index, and systemic vascular resistance index in emergency department patients with poorly controlled hypertension; and to determine the frequency in which antihypertensive drugs prescribed do not address the predominant haemodynamic abnormality. METHODS: This cross-sectional observational study was conducted in an emergency department of a 1400-bed tertiary hospital in Hong Kong. Patients aged 18 years or above, with systolic blood pressure of ≥160 mm Hg or diastolic blood pressure of ≥100 mm Hg based on two or more measurements and on two separate occasions within 2 to 14 days, were included. Haemodynamic measurements were obtained using a non-invasive Doppler ultrasound monitor. Doctors were blinded to the haemodynamic data. Any antihypertensive medication adjustment was evaluated for correlation with haemodynamic changes. RESULTS: Overall, 164 patients were included. Their mean age was 69.0 years and 97 (59.1%) were females. Systemic vascular resistance and cardiac output were elevated in 65.8% (95% confidence interval, 57.9-72.9%) and 15.8% (10.8-22.5%) of patients, respectively. Systemic vascular resistance index and cardiac index were elevated in 43.9% (95% confidence interval, 36.2-51.8%) and 19.5% (13.9-26.5%) of patients, respectively. Of 71 patients in whom antihypertensive medications were adjusted, 25 (35.2%; 95% confidence interval, 24.5-47.5%) were prescribed agents that did not correlate with the primary haemodynamic abnormality. CONCLUSIONS: The profile of haemodynamic changes in emergency department patients with poorly controlled hypertension is characterised. The antihypertensive drugs prescribed did not correspond to the patient's primary haemodynamic derangement in 35% of cases.

Prospective validation of Thrombolysis in Myocardial Infarction and front door Thrombolysis in Myocardial Infarction risk scores in Chinese patients presenting to the ED with chest pain.

BACKGROUND: Chest pain is a common complaint among emergency department (ED) patients. The Thrombolysis in Myocardial Infarction (TIMI) and front door TIMI (FDTIMI) scores are used to risk stratify chest pain patients in many Western countries; they have not been validated in patients with undifferentiated chest pain in Asia. Our objective was to establish the relationship between the TIMI and FDTIMI scores and the 30 day rate of major adverse cardiac outcomes (MACE) in Chinese patients presenting to the ED with chest pain. METHODS: Prospective, single-center, observational cohort study of consecutive patients presenting with chest pain from July 2009 until March 2010 to a Hong Kong university hospital ED. Data collected included patient characteristics, TIMI items and past medical and medication history. Primary outcome was MACE within 30 days of presentation. MACE was a composite outcome of any of the following: death (all causes), readmission with myocardial infarction, acute coronary syndrome not diagnosed at initial ED presentation and coronary revascularization. RESULTS: One thousand patients recruited with complete 30-day follow-up. STEMI patients (n = 75) were excluded. Mean patient age 66.8 ± 13.9 years; 51.7% male. 119 (12.9%) patients had MACE within 30 days of presentation. The incidence of MACE ranged from 0 for TIMI0 to 37.5% for patients with TIMI6/7. Increasing TIMI and FDTIMI scores were associated with a higher incidence of MACE. CONCLUSIONS: This validation suggests that the TIMI/FDTIMI scores can be employed in Hong Kong Chinese; they may be useful for risk stratification of Chinese ED patients with undifferentiated chest pain elsewhere.

CardioDetect rapid test for the diagnosis of early acute myocardial infarction.

Two hundreds patients suspected of acute myocardial infarction presenting to the hospital with a median symptom onset of 2.3 h (IQR 1.7-4.0 h) were enrolled in this study. The diagnostic performances of CardioDetect®, a one-step immunotest for heart-type fatty acid-binding protein (H-FABP), and its combination with cardiac troponin I (cTnI) at admission and 2 h after admission, were compared with different cardiac markers. The H-FABP immunotest had better sensitivities (76.6% and 94.4%) than the other cardiac markers and better specificities (88.2% and 81.7%) than myoglobin at admission and 2 h after admission. Both sensitivity and negative predictive value increased to over 90.0% at 2 h after admission. The areas under the receiver operator characteristic curve for the combination of H-FABP with cTnI were the greatest at admission [0.834 (95% CI: 0.774-0.894)].

The normal ranges of cardiovascular parameters measured using the ultrasonic cardiac output monitor.

The ultrasonic cardiac output monitor (USCOM) is a noninvasive transcutaneous continuous wave Doppler method for assessing hemodynamics. There are no published reference ranges for normal values in adults (aged 18-60 years) for this device. This study aimed to (1) measure cardiovascular indices using USCOM in healthy adults aged 18-60 years; (2) combine these data with those for healthy children (aged 0-12), adolescents (aged 12-18), and the elderly (aged over 60) from our previously published studies in order to present normal ranges for all ages, and (3) establish normal ranges of USCOM-derived variables according to both weight and age. This was a population-based cross-sectional observational study of healthy Chinese subjects aged 0.5-89 years in Hong Kong. USCOM scans were performed on all subjects, to produce measurements including stroke volume, cardiac output, and systemic vascular resistance. Data from previously published studies (children, adolescents, and the elderly) were included. Normal ranges were defined as lying between the 2.5th and 97.5th percentiles. A total of 2218 subjects were studied (mean age = 16.4, range = 0.5-89; 52% male). From previous studies, 1197 children (aged 0-12, 55% male), 590 adolescents (aged 12-18, 49% male), and 77 elderly (aged 60-89, 55% male) were included. New data were collected from 354 adults aged 18-60 (47% male). Normal ranges are presented according to age and weight. We present comprehensive normal ranges for hemodynamic parameters obtained with USCOM in healthy subjects of all ages from infancy to the elderly.

Rapid analysis of fatty acid-binding proteins with immunosensors and immunotests for early monitoring of tissue injury.

Fatty acid-binding protein (FABP) holds promise for early detection of tissue injury. This small protein (15kD) appears earlier in the blood than large proteins after cell damage. Combined its characteristics of high concentration tissue contents and low normal plasma values provide the possibility of a rapid rise above the respective reference values, and thus an early indication of the appearance of tissue injury. A general review was presented on the current status of different types of FABP for the detection of tissue injury in patients with myocardial injury, brain injury and also in athletes or horses with skeletal muscle injury. To take full advantage of the characteristics of the early marker FABP, rapid analysis is a crucial parameter. In this review, an overview of the development of immunoassay for the quantification of FABP in buffer, plasma or whole blood was outlined. The characteristics of different FABP immunosensors and immunotests were described. The feasibility of these immunoassays to be used in routine clinical practice and in emergency case was also discussed. Nowadays, the improved automated immunoassays (e.g. a microparticle-enhanced turbidimetric immunoassay), less time-consuming bedside immunosensors and immunotests (e.g. a one-step FABP lateral flow immunotest), are the main advance technology in point-of-care testing. With these point-of-care tests, the application of FABP as an early tissue injury marker has a great potential for many clinical purposes.

Learning profiles for noninvasive transcutaneous Doppler ultrasound.

OBJECTIVE: This study aimed to establish learning profiles for noninvasive transcutaneous Doppler ultrasound. MATERIALS AND METHODS: Four trainees attended a 2-h lecture, followed by a 15-min demonstration on a volunteer and a 30-min hands-on workshop in a small group setting. Then, they underwent hands-on practice on 50 participants without supervision. The skill acquisitions in terms of signal magnitude, signal quality, and measurement time of the trainees were evaluated through 50 assessments, and were compared with that of a trainer with extensive experience on the use of an ultrasonic cardiac output monitor acting as a 'gold standard'. The learning profile for each individual trainee was analyzed using the cumulative sum graphical method. RESULTS: Four trainees performed ultrasonic cardiac output monitor on 50 participants. All trainees attained proficiency after 18-36 assessments to achieve aortic signal magnitude and quality comparable with the trainer. It requires a minimum of nine assessments to obtain three aortic scans within 5 min with 95% success rates. Only half of the trainees achieved competence in pulmonary scans and the minimum number of assessments required was 36. A minimum of 22 assessments were required for three pulmonary scans within 10 min with 95% success rates. CONCLUSION: A substantial period of learning needs to be undertaken to achieve proficiency on the use of noninvasive transcutaneous Doppler ultrasound. Cumulative sum analysis is a useful tool for ongoing quality assessment during medical education and training in practical procedures on an individual basis.

Development of a quantitative lateral-flow assay for rapid detection of fatty acid-binding protein.

Using human heart-type fatty acid-binding protein (H-FABP) as an early cardiac marker to confirm or exclude a diagnosis of acute myocardial infarction (AMI) soon after admission requires a rapid assay system. Due to the requirement of skillful technicians and complicated assay procedures, most immunochemical assays for H-FABP are of limited use for routine clinical practice. In the present study, we describe a rapid lateral-flow assay for detection of H-FABP. Fifty-one human samples were evaluated using a conventional ELISA and a newly developed lateral-flow assay. A good agreement between the two methods was found according to Bland and Altman plot. The correlation found was y=0.9685 x -0.6270 (r(2)=0.9585). The detector antibody labeled with colloidal gold was mixed with those without label to extend the linear range of the calibration curve up to 125 microg/l H-FABP with r(2)=0.9832. The detection limit of the assay was 2.8 microg/l. The test-strips can be stored either at 4 degrees C and room temperature for up to 1 year without significant loss of activity. Finally, a one-step FABP test so-called CardioDetect(R), which was derived from the serum lateral-flow assay has been designed for qualitative determination of H-FABP in whole blood samples. It requires no sample pretreatment and gives results within 15 min. Thirty-eight patients presenting with chest pain and suspected AMI were studied. Using an upper reference level of 7 microg/l, the specificity of the rapid test was 94%. Both sensitivity and negative predictive value (NPV) were 100%, implying that 100% of non-AMI patients could be excluded with no false-negative results. With this rapid and sensitive immunotest, H-FABP could soon be introduced into clinical practice.

Early time-dependent dynamic changes of TBET and GATA3 mRNA expressions in patients with acute coronary syndrome.

BACKGROUND: T-box expressed in T cells (TBET) and guanine adenine thymine adenine sequence-binding protein 3 (GATA3) play important roles in the differentiation of Th1 and Th2 subsets, which contributes to the progression of acute coronary syndrome (ACS). OBJECTIVE: This study aimed to investigate the temporal change of TBET/GATA3 mRNA ratio in ACS. METHODS: Thirty-three patients suspected of ACS with symptom onset within 24 hours were recruited. Blood samples were taken after arrival at the emergency department and at hourly intervals until the 6th hour. The mRNA expressions of TBET and GATA3 were quantified by a real-time RT-qPCR. RESULTS: The TBET/GATA3 mRNA ratio was elevated dramatically in patients with acute myocardial infarction (AMI) and exhibited biphasic M-shaped release kinetics with two distinct peaks. The ratio was elevated 2 hours after symptom onset, dropped to the lowest level at 10 hours, and rose to the second peak at 14 hours. A similar biphasic M-shaped curve was observed in AMI patients with blood samples taken prior to any intervention. CONCLUSIONS: The TBET/GATA3 mRNA ratio was elevated in AMI patients throughout most of the first 20 hours after symptom onset. The biphasic M-shaped release kinetics was more likely to reflect pathophysiological changes rather than treatment effects.

Matrix metalloproteinase 9 mRNA: an early prognostic marker for patients with acute stroke.

OBJECTIVES: To investigate matrix metalloproteinase 9 (MMP9) mRNA as a prognostic marker in stroke. DESIGN AND METHODS: MMP9 mRNA concentrations in 126 stroke patients were analyzed using quantitative reverse transcription-polymerase chain reaction. RESULTS: The normalized MMP9 mRNA concentration was almost 3 times higher in non-survival patients compared to survival patients (P=0.0002); and 1.9-fold higher in patients with post-stroke modified Rankin score (mRS) >2 than patients with mRS≤2 (P<0.05). CONCLUSIONS: MMP9 mRNA was a predictor of poor outcome and mortality in stroke.

Cardiac multi-marker strategy for effective diagnosis of acute myocardial infarction.

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a heart-specific and highly sensitive biomarker for early diagnosis of acute myocardial infarction (AMI). We investigated the effectiveness of H-FABP for diagnosis of AMI in patients with different ethnic background and different time from symptom onset. METHODS: Venous blood was withdrawn from consecutive patients with acute chest pain admitted to the First Affiliated Hospital of Xinjiang Medical University. The blood samples were used for measurement of creatine kinase MB (CK-MB) and cardiac troponin I (cTnI) using Beckman Coulter DC-800 analyzer, and detection of H-FABP using a one-step bedside immunotest. RESULTS: Two hundred and eighty-nine patients admitted within 12h after the onset of symptoms were recruited in the study. The H-FABP immunotest was found to have higher diagnostic accuracy than cTnI and CK-MB in patients admitted within 3h. The combination of H-FABP and cTnI was found to have the highest diagnostic accuracy (91%) among different cardiac markers and the other combinations. It gave the highest sensitivity [96% (95% CI: 91-98%)] and a comparable specificity [84% (95% CI: 76-89%)] to cTnI alone. CONCLUSION: A cardiac panel consisting of H-FABP and troponin is recommended.

Diagnostic utility of CRP to neopterin ratio in patients with acute respiratory tract infections.

OBJECTIVES: In this study we aimed to investigate the roles of neopterin, C-reactive protein (CRP) and the CRP to neopterin (C/N) ratio to differentiate bacterial from viral aetiology in patients with suspected acute respiratory tract infections (ARTIs) presenting to the emergency department (ED). METHODS: Serum was taken from five hundred and sixty-one patients and used to measure neopterin and CRP levels. The primary outcome was bacterial or viral infection based on positive bacterial culture and positive viral serology. Patients were classified as either: group 1 with positive bacterial culture and mixed bacterial/viral growth; group 2 with virological aetiology, and group 3 with unknown microbiological aetiology. RESULTS: The median of the C/N ratio was 10 times higher in patients with bacterial aetiology than with viral aetiology (12.5 vs 1.2mg/nmol; P<0.0001), and 42 times higher than those in healthy subjects (12.5 vs 0.3mg/nmol; P<0.0001). The area under the receiver-operator characteristic curve for the C/N ratio was 0.840 (0.783-0.898; P<0.05). A cut-off value of "C/N ratio >3" for ruling in/out bacterial/viral infection yielded optimal sensitivity and specificity of 79.5% and 81.5% respectively. A sensitivity analysis performed on all patients (including unknown aetiology) with a cut-off value of "C/N ratio >3" yields a best-case scenario for ruling in/out bacterial/viral infection with sensitivity of 93.1% and specificity of 93.0%. CONCLUSION: This study shows that CRP and neopterin have a role in differentiating bacterial from viral causes of ARTI, and the C/N ratio yields optimal differentiation in the ED setting.

Detection of serum neopterin for early assessment of dengue virus infection.

OBJECTIVE: Neopterin is generated and released in increased amounts by macrophages upon activation by interferon-gamma during Th1-type immune response. The potential usefulness of neopterin in early prognostic information of dengue virus infection was investigated. METHODS: Neopterin concentrations were determined in serum samples from 110 dengue fever (DF) patients. The neopterin levels were compared with those in 50 measles and 40 influenza patients; 155 healthy blood donors served as controls. RESULTS: In acute sera of DF patients mean neopterin concentration was 48.2 nmol/L, which was higher than that in patients with measles (mean: 36.3 nmol/L) and influenza (18.8 nmol/L) and in healthy controls (6.7 nmol/L; P<0.001). In the patients with confirmed DF, an early neopterin elevation was detected already at the first day after the onset of symptoms and rose to a maximum level of 54.3 nmol/L 4 days after the onset. Higher increase of neopterin level in DF patients was associated with longer duration of fever and thus predicted the clinical course of the disease. CONCLUSIONS: Neopterin concentrations were found significantly higher in DF patients compared with healthy controls and also with other viral infections (P<0.001) and may allow early assessment of the severity of DF.

Serum neopterin for early assessment of severity of severe acute respiratory syndrome.

Neopterin and C-reactive protein (CRP) concentrations were determined in serum samples from 129 severe acute respiratory syndrome (SARS) patients and 156 healthy blood donors. In the patients with confirmed SARS, an early neopterin elevation was detected already at the day of onset of symptoms and rose to a maximum level of 45.0 nmol/L 3 days after the onset. All SARS patients had elevated neopterin concentrations (>10 nmol/L) within 9 days after the onset. The mean neopterin concentrations were 34.2 nmol/L in acute sera of SARS patients, 5.1 nmol/L in convalescent sera, and 6.7 nmol/L in healthy controls. In contrast, the mean CRP concentrations in both acute and convalescent sera of SARS patients were in the normal range (<10 mg/L). Serum neopterin level in SARS patients was associated with fever period and thus the clinical progression of the disease, while there was no significant correlation between the CRP level and the fever period. Serum neopterin may allow early assessment of the severity of SARS. The decrease of neopterin level was found after steroid treatment, which indicates that blood samples should be collected before steroid treatment for the neopterin measurement.