European consensus for the diagnosis of MCI and mild dementia: Preparatory phase.

INTRODUCTION: Etiological diagnosis of neurocognitive disorders of middle-old age relies on biomarkers, although evidence for their rational use is incomplete. A European task force is defining a diagnostic workflow where expert experience fills evidence gaps for biomarker validity and prioritization. We report methodology and preliminary results. METHODS: Using a Delphi consensus method supported by a systematic literature review, 22 delegates from 11 relevant scientific societies defined workflow assumptions. RESULTS: We extracted diagnostic accuracy figures from literature on the use of biomarkers in the diagnosis of main forms of neurocognitive disorders. Supported by this evidence, panelists defined clinical setting (specialist outpatient service), application stage (MCI-mild dementia), and detailed pre-assessment screening (clinical-neuropsychological evaluations, brain imaging, and blood tests). DISCUSSION: The Delphi consensus on these assumptions set the stage for the development of the first pan-European workflow for biomarkers' use in the etiological diagnosis of middle-old age neurocognitive disorders at MCI-mild dementia stages. HIGHLIGHTS: Rational use of biomarkers in neurocognitive disorders lacks consensus in Europe. A consensus of experts will define a workflow for the rational use of biomarkers. The diagnostic workflow will be patient-centered and based on clinical presentation. The workflow will be updated as new evidence accrues.

Blood biomarkers in ischemic stroke: potential role and challenges in clinical practice and research.

Fast and accurate diagnosis of stroke is crucial for the immediate application of the right therapy to patients. However, rapid diagnosis is still a challenge since an ischemic stroke cannot be identified based only on clinical assessment. CT or MRI imaging is required to rule out hemorrhagic stroke since thrombolytic therapy can lead to increased intracranial bleeding and further aggravation of hemorrhagic stroke. In addition, clinical situations that imitate the signs and symptoms of stroke may also impede the rapid diagnosis and treatment of stroke victims. It is therefore of value to discover non-invasive tests that aim to quickly distinguish stroke from stroke mimics and distinguish ischemic from hemorrhagic stroke. Identifying blood biomarkers of stroke is an active area of research since their potential use is not limited to diagnosis and differentiation, but can be applied to prognosis and patient monitoring - monitoring the effectiveness of applied therapy and/or diagnose possible complications. However, their use has been limited so far not only for reasons related to patients and the disease (heterogeneity of stroke etiology, the complexity of the ischemic cascade, the impact of the blood-brain barrier (BBB) on diffusion of blood biomarkers, and difficulties in obtaining consent from stroke patients) but also for reasons that related to laboratory measurement of these biomarkers (pre-analytical and analytical issues as well as interpretation of laboratory measurements). Until today, many biomarkers have been identified, however none so far have shown sufficient sensitivity and specificity in order to be used in the clinical setting. In this review, we will focus on ischemic stroke and we aim to highlight these problems and also investigate if these are due to stroke complexity or due to our limited knowledge of pre-analytical requirements for many of these molecules and the questionable quality of the assays used.

Maternal serum levels of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9) and their complex MMP-9/NGAL in pregnancies with preeclampsia and those with a small for gestational age neonate: a longitudinal study.

BACKGROUND: The aim of this study was to determine maternal serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinase-9 (MMP-9), and MMP-9/NGAL complex longitudinally in pregnancy, in normal pregnancies, in pregnancies that developed preeclampsia and in pregnancies that delivered a small for gestational age infant (SGA). METHODS: Neutrophil gelatinase-associated lipocalin, MMP-9, and MMP-9/NGAL were determined in the first, second, and third trimesters in 33 normal pregnancies, 12 pregnancies complicated by preeclampsia, and 14 pregnancies that delivered a SGA neonate. RESULTS: Median NGAL concentration (ng/mL) in normal pregnancies increased significantly from 12.8 in the first trimester to 25.9 in the second trimester (p = 0,002) and 48.0 (p < 0.0001) in the third trimester. In preeclamptic pregnancies, NGAL was significantly higher, compared with normal pregnancies, in the first (30.9; p = 0.006) and second (44.6; p = 0.015) trimesters. MMP-9 and MMP-9/NGAL complex concentrations in preeclamptic pregnancies did not differ significantly from normal pregnancies in either trimester. Pregnancies with an SGA infant did not have different marker concentrations in either trimester, compared with normal pregnancies. CONCLUSION: Maternal serum NGAL, MMP-9, and MMP-9/NGAL complex concentrations tend to increase during pregnancy in normal and preeclamptic pregnancies. NGAL was significantly elevated in the first and second trimesters, in pregnancies that later developed preeclampsia.

European intersocietal recommendations for the biomarker-based diagnosis of neurocognitive disorders.

The recent commercialisation of the first disease-modifying drugs for Alzheimer's disease emphasises the need for consensus recommendations on the rational use of biomarkers to diagnose people with suspected neurocognitive disorders in memory clinics. Most available recommendations and guidelines are either disease-centred or biomarker-centred. A European multidisciplinary taskforce consisting of 22 experts from 11 European scientific societies set out to define the first patient-centred diagnostic workflow that aims to prioritise testing for available biomarkers in individuals attending memory clinics. After an extensive literature review, we used a Delphi consensus procedure to identify 11 clinical syndromes, based on clinical history and examination, neuropsychology, blood tests, structural imaging, and, in some cases, EEG. We recommend first-line and, if needed, second-line testing for biomarkers according to the patient's clinical profile and the results of previous biomarker findings. This diagnostic workflow will promote consistency in the diagnosis of neurocognitive disorders across European countries.

Neurophil gelatinase-associated lipocalin as a new biomarker in laboratory medicine.

Neutrophil gelatinase-associated lipocalin (NGAL) is a 25 kDa protein of the lipocalin superfamily. This protein is expressed and secreted by immune cells, hepatocytes, and renal tubular cells in various pathologic states. NGAL has recently generated great interest as an early biomarker of renal injury. However, like many other endogenous biomarkers it is not produced by just one cell type and it exists in more than one molecular form. As recent research has shown different pathological conditions may involved in the production of this molecule. This review summarizes the current knowledge about the biology of NGAL and examines the role of this molecule of acute renal injury as well as in other pathologic conditions like neoplasia, anemia, pregnancy, cardiovascular disease chronic kidney disease and in cardiorenal syndrome. Commercial and research immunoassays are used to measure NGAL in both plasma and urine but these assays are not standardized. The existence of different molecular forms of NGAL and their expression at various disease states further complicates the interpretation of the results. Pre analytical issues and biological variation are also not fully elucidated.

Effects of walking on heart rate recovery, endothelium modulators and quality of life in patients with heart failure.

BACKGROUND: Few studies have addressed the impact of moderate unsupervised everyday physical activity in patients with chronic heart failure (CHF). DESIGN: We investigated the effects of a 12-week walking programme as the sole exercise intervention on heart rate recovery (HRR), index of the autonomic system equilibrium, serum modulators of endothelial function (i.e. asymmetric dimethylarginine (ADMA) and homocysteine), markers of inflammation and oxidative stress and quality of life measures (i.e. SF-36 and the Zung depression scale) in CHF patients. METHODS: Twenty-eight stabilized CHF patients of ΝYHΑ class II and III volunteered to participate either in the exercise (n = 18) or in the non-exercise (n = 10) groups. Ten age-matched healthy volunteers provided reference values. The exercise programme consisted of unsupervised 40-minute walking for five days per week. RESULTS: Repeated measures ANOVA revealed significant improvements in HRR (p < 0.001) in the exercise patients compared to their non-exercise counterparts. ADMA levels in CHF patients at baseline were found higher than the healthy reference volunteers (p < 0.03), while a decrease in ADMA levels after walking was associated with HRR changes (r = 0.74, p = 0.007). Homocysteine levels both at baseline and at the end of the walking intervention decreased in the exercise group, but were still higher than in the healthy individuals. Average walking distance positively correlated with homocysteine decrease (p < 0.05). Total SF-36 score significantly improved (p < 0.02) mainly due to enhancements in the physical component score (p < 0.026). CONCLUSION: A 12-week unsupervised walking programme exhibits a pronounced HRR amelioration, possibly attenuates endothelial damage and induces a concomitant improvement in perceived quality of life in CHF patients.

The Greek way to the Register: the establishment and operation of the Register for Clinical Chemists-Clinical Biochemists in Greece.

In Greece, there is no officially organized training in clinical chemistry for scientists. The Greek Society of Clinical Chemistry-Clinical Biochemistry (GSCC-CB), following the encouragement of the EC4/RC decided to organize a voluntary Register for specialists in clinical chemistry. The following criteria for registration were defined: 1) University degree in Chemistry, Biochemistry, Biology, Medicine, Pharmacy or other relevant subject. 2) A total of 9 years of university studies and postgraduate specialization in clinical chemistry-clinical biochemistry. 3) A minimum of 4 years of postgraduate specialization in clinical chemistry-clinical biochemistry on the job. 4) The candidate must be practicing clinical chemistry-clinical biochemistry in a laboratory in a medical environment in Greece. The postgraduate specialization in clinical chemistry-clinical biochemistry includes the laboratory training and the theoretical education. The laboratory training is organized by the GSCC-CB according to the Professional Training Dossier. The theoretical education was organized in a series of 18 "Seminars" which was the content of the "Educational program" of the GSCC-CB. Successful completion of the Educational program leads to a Certificate of Competence. The Greek Register has gained equivalence with the EC4 Register and it has 218 members, more than 80 of whom are European clinical chemists.

Inter-Laboratory Comparisons and EQA in the Mediterranean Area.

The role of Proficiency Testing schemes (PT) or External Quality Control programs (EQA), involves the use of inter-laboratory comparisons for the determination of laboratory performance. EQA-PT schemes are of primordial importance to the analytical quality, standardization of methods and harmonization of the results. Laboratories are familiar with EQA-PT schemes as they are a prerequisite for their accreditation according to the ISO/IEC 15189 standard. The IFCC Committee on Proficiency Testing (C-PT) conducted a survey among the colleagues of the Mediterranean countries in order to evaluate the status of the EQA-PT providers in the region, their acceptance among laboratories, and possible issues in their implementation. The survey was organized electronically and we received 59 replies from colleagues (IFCC National Representatives and affiliated EQA-PT providers), from 17 of the 23 countries (74%) of the Mediterranean area. We concluded that there is a broad difference in the application of the rules of External Quality Control programs or Proficiency Testing schemes, among the Laboratories in the Mediterranean countries. Moreover, as the Accreditation of the Laboratories is not mandatory in the majority of these countries, there is no valid reason for participation in EQA-PT schemes.

Prediction of pre-eclampsia combining NGAL and other biochemical markers with Doppler in the first and/or second trimester of pregnancy. A pilot study.

OBJECTIVE: To determine the performance of maternal characteristics, Doppler and a set of biochemical markers for pre-eclampsia (PE) screening at 11+0 to 13+6 and 20+1 to 25+6 weeks' gestation. STUDY DESIGN: Prospectively enrolled women at 11+0 to 13+6 and 20+1 to 25+6 weeks. Maternal characteristics, uterine artery pulsatility index (UtA-PI), ductus venosus pulsatility index (DV-PI) and serum biomarkers including pregnancy associated plasma protein - A (PAPP-A), placental growth factor (PlGF), soluble fms-like tyrosine kinase 1 (sFlt-1), s-Flt-1/PLGF ratio, asymmetric dimethylarginine (ADMA), matrix metalloproteinase 9 (MMP-9), neutrophil gelatinase-associated lipocalin (NGAL) and MMP-9/NGAL complex were recorded. RESULTS: Combination of NGAL and BMI in a logistic regression model detected 70% of PE in the first trimester (p=0.001). Including UtA-PI and DV-PI in the model sensitivity reached 77.8% with 96.6% specificity (p=0.004). Combination of second trimester NGAL and s-Flt-1/PLGF ratio yield specificity 100% (p=0.001). Combination of second trimester UtA-PI with first trimester NGAL, BMI and age detected 80% of PE with specificity 91.9% (p=0.001). CONCLUSION: Combination of NGAL, maternal characteristics and Doppler parameters in the first and/or second trimester can detect a consistent number of PE pregnancies. NGAL is a potent new biomarker for the prediction of preeclampsia.

Placental growth factor and soluble fms-like tyrosine kinase-1 are useful markers for the prediction of preeclampsia but not for small for gestational age neonates: a longitudinal study.

OBJECTIVE: To determine maternal serum concentrations of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) longitudinally in normal pregnancies, pregnancies that developed preeclampsia and pregnancies that deliver a small for gestational age (SGA) infant, in order to evaluate them as markers for the prediction of preeclampsia. STUDY DESIGN: In this case-control study we included 12 singleton pregnancies that developed preeclampsia and 104 randomly selected singleton normal pregnancies. Fourteen of the normal pregnancies gave birth to an SGA infant. Blood samples and ultrasonographic data were collected during the 1st, 2nd and 3rd trimesters of pregnancy. RESULTS: In preeclamptic pregnancies, PlGF (pg/mL) (median; inter-quartile range) was significantly lower in the 2nd (208; 84-339) (p=0.035) and in the 3rd trimester (202; 109-284) (p=0.002) while sFlt-1 was significantly higher only in the 3rd trimester (2521; 2101-3041) (p=0.011) compared to normal pregnancies (PlGF 2nd: 311; 243-440, PlGF 3rd: 780; 472-1037, sFlt-1 3rd: 1616; 1186-2220). In pregnancies with SGA infants, PlGF and sFlt-1 did not differ significantly from normal pregnancies in any trimester. The sFlt-1 to PlGF ratio was significantly higher in preeclamptic pregnancies than in normal pregnancies, in both the 2nd and 3rd trimesters. The relative difference and the slope of PlGF concentration between 1st and 2nd trimester were significantly reduced in preeclampsia compared to normal pregnancies. A logistic regression model with predictors BMI, 2nd trimester Doppler PI and relative difference of PlGF from the 1st to the 2nd trimester gave 46% sensitivity and 99% specificity for the prediction of preeclampsia, with a very high negative predictive value of 98.3%. CONCLUSIONS: Our study confirms that maternal serum PlGF concentration is significantly lower, at least after 20th week, while sFlt-1 concentration is significantly higher in 3rd trimester, in pregnancies destined to develop preeclampsia. Pregnancies that gave birth to SGA infants do not have altered angiogenic factor concentrations throughout pregnancy. The relative difference of PlGF from the 1st to the 2nd trimester, uterine artery Doppler PI in the 2nd trimester and BMI are the most powerful markers for the prediction of preeclampsia.

Levels of asymmetric dimethylarginine throughout normal pregnancy and in pregnancies complicated with preeclampsia or had a small for gestational age baby.

OBJECTIVE: The aim of this study was to investigate maternal asymmetric dimethylarginine (ADMA) concentrations at the three trimesters of pregnancy in uncomplicated pregnancies and in women who developed preeclampsia or had small for gestational age infants (SGA) without preeclampsia. METHODS: ADMA concentrations were retrospectively determined in the first, second and third trimester of pregnancy in 41 uncomplicated pregnancies, 10 pregnancies complicated with preeclampsia and 14 pregnancies that delivered a SGA baby. ADMA was measured with an ELISA kit. RESULTS: Mean (±SD) concentrations of ADMA (µmol/L) in uncomplicated l pregnancies were: 0.51 ± 0.14; 0.52 ± 0.13; 0.58 ± 0.16 in the three trimesters, respectively. ADMA concentrations in SGA pregnancies were significantly lower in each trimester compared to uncomplicated pregnancies: (0.40 ± 0.10, p = 0.005 1st trim; 0.42 ± 0.10, p = 0.007 2nd trim; 0.45 ± 0.10, p = 0.007 3rd trim). Although pregnancies that developed preeclampsia had higher ADMA concentration in all trimesters compared to uncomplicated pregnancies (0.58 ± 0.10; 0.63 ± 0.14; 0.68 ± 0.11), the difference was statistically significant only in the 2nd trimester (p = 0.02). CONCLUSIONS: Maternal serum ADMA concentration tends to increase during normal pregnancy. Pregnancies with SGA infants had significantly lower ADMA levels in all trimesters of pregnancy. ADMA concentrations in the 2nd trimester was significantly elevated in pregnancies that later developed preeclampsia.

Connection between telomerase activity in PBMC and markers of inflammation and endothelial dysfunction in patients with metabolic syndrome.

Metabolic syndrome (MS) is a constellation of metabolic derangements associated with vascular endothelial dysfunction and oxidative stress and is widely regarded as an inflammatory condition, accompanied by an increased risk for cardiovascular disease. The present study tried to investigate the implications of telomerase activity with inflammation and impaired endothelial function in patients with metabolic syndrome. Telomerase activity in circulating peripheral blood mononuclear cells (PBMC), TNF-α, IL-6 and ADMA were monitored in 39 patients with MS and 20 age and sex-matched healthy volunteers. Telomerase activity in PBMC, TNF-α, IL-6 and ADMA were all significantly elevated in patients with MS compared to healthy volunteers. PBMC telomerase was negatively correlated with HDL and positively correlated with ADMA, while no association between TNF-α and IL-6 was observed. IL-6 was increasing with increasing systolic pressure both in the patients with MS and in the healthy volunteers, while smoking and diabetes were positively correlated with IL-6 only in the patients' group. In conclusion, in patients with MS characterised by a strong dyslipidemic profile and low diabetes prevalence, significant telomerase activity was detected in circulating PBMC, along with elevated markers of inflammation and endothelial dysfunction. These findings suggest a prolonged activity of inflammatory cells in the studied state of this metabolic disorder that could represent a contributory pathway in the pathogenesis of atherosclerosis.

Study of insulin resistance, TNF-α, total antioxidant capacity and lipid profile in patients with chronic heart failure under exercise.

Gluco-metabolic syndrome, oxidative stress and inflammation are common in chronic heart failure (CHF). Exercise training programmes are known to improve oxidative status, insulin sensitivity and endothelial function. In this study, the effects of walking on improving lipid and glucose metabolism in CHF patients, under statin treatment, were investigated. Fasting glucose, serum insulin, tumor necrosis factor-α (TNF-α), total antioxidant capacity (TAC), uric acid (UA), total cholesterol, triglycerides, high-density lipoproteins (HDL), direct low-density lipoproteins (LDL-dir), apolipoprotein-B, apolipoprotein-A1, and lipoprotein-a (Lp(a)) were monitored. Insulin resistance was depicted by fasting insulin resistance index (FIRI) (FIRI≥2.94±1.41). HDL significantly increased with walking and was positively correlated with the non-significant triglyceride decrease and significant Lp(a) decrease. Significant correlations were found in all CHF patients at baseline between FIRI and New York Heart Association (NYHA) functional class, ejection fraction, HDL, triglycerides and TNF-α. All non-diabetic CHF patients were characterized by insulin resistance. Serum insulin and fasting glucose significantly decreased with walking, while decrease in FIRI was positively associated with patients' adherence to the walking program. Elevated uric acid and TNF-α levels also significantly decreased. In conclusion, the present study demonstrated that moderate, unsupervised, everyday physical activity was able to ameliorate the lipid and glycemic profile of CHF patients, with simultaneous attenuation of inflammation and oxidative stress.

Homocysteine and metalloprotease-3 and -9 in patients with ascending aorta aneurysms.

INTRODUCTION: Matrix metalloprotease (MMP) activity is increased in ascending and abdominal aortic aneurysms. Elevated plasma homocysteine (Hc) levels have been reported in patients with abdominal aneurysms. However, there are no published reports correlating, Hc and MMP levels in patients with ascending aortic aneurysms (AAAs). MATERIALS AND METHODS: This study attempts to determine whether serum or tissue Hc in patients undergoing surgery for AAAs is associated with aneurysm diameter, circulating and tissue levels of MMP-3 and MMP-9 assessed by Enzyme-linked immunosorbent assay (ELISA) and their mRNA tissue expression assessed by real-time PCR. Twenty-seven patients were recruited in the study. RESULTS: Forty-three percent of the patients had abnormal Hc serum levels (>35.9 µmol/L). Circulating MMP-3 (6.44±4.20 ng/mL) and MMP-9 levels (134±11.4 ng/mL) were elevated compared to healthy controls (p<0.001). Positive correlations were observed between circulating MMP-9, tissue MMP-3 and MMP-9 concentrations with serum Hc (r=0.773, p=0.011; r=0.461, p=0.014; r=0.526, p=0.024, respectively). MMP-9 mRNA was expressed in 21% of the aneurysms. No MMP-3 mRNA expression was detected in the studied specimens. A negative correlation between tissue Hc and aneurysm diameter was detected. No associations of serum Hc, MMP-3 and MMP-9 levels in both serum and tissue with aneurysm diameter were noted. CONCLUSION: Our results suggest that Hc, even in patients with mild hyperhomocysteinaemia, is involved in the pathophysiology of AAA, through the regulation of MMP-3 and MMP-9 activity.

The organization of an educational program for specialists in clinical chemistry by the Greek Society of Clinical Chemistry-Clinical Biochemistry.

In Greece, there is no officially organized training in clinical chemistry for scientists. The Greek Society of Clinical Chemistry-Clinical Biochemistry decided to organize an intensive educational program of 18 seminars on clinical chemistry content as it is described in the EC4 Syllabus. The duration of each seminar was about 6 hours and consisted of 6 to 9 lectures. At the end of each seminar there was a voluntary written examination, comprised of 24 multiple choice questions. Successful completion of the Educational program was leading to a Certificate of Competence. Two cycles of the 18 seminars were performed: 1st cycle from October 2003 to December 2005 and 2nd cycle from March 2005 to October 2007. One hundred eighty nine colleagues was the mean attendance per seminar for the seminars of the 1st cycle and 38 colleagues for the seminars of the 2nd cycle. The mean participation to the examination for each seminar was almost 80% for the 1st cycle and 68% for the 2nd cycle. More than 80% of the participants performed Good or Very good in the examination in both cycles. It is estimated that more than 40% of the scientists who practice Clinical Chemistry in Greece, participated to this educational activity. This program is now provided as an e-learning application, and it is open for all scientists who want to follow the discipline of clinical chemistry.

Association of neutrophil gelatinase-associated lipocalin with the severity of coronary artery disease.

Serum neutrophil gelatinase-associated lipocalin (NGAL) concentrations were measured in 73 consecutive patients who underwent first-time angiography for suspected coronary artery disease (CAD), and their associations with angiographic indexes of the severity of CAD (i.e., number of diseased vessels and modified Gensini score) were estimated. Median serum NGAL levels in patients with angiographically confirmed CAD were significantly higher than those in patients with normal coronary arteries (29.0 ng/ml [interquartile range 25.2 to 36.8] vs 22.4 ng/ml [interquartile range 17.34 to 32.0], p = 0.004). Statistically significant correlations were observed between serum NGAL level and the number of diseased vessels (r(s) = 0.390, p = 0.01) and modified Gensini score (r(s) = 0.356, p = 0.002). Using multivariate analysis, serum NGAL level was independently associated with the presence and severity of CAD. In conclusion, serum NGAL levels are significantly higher in the presence of CAD and are correlated with the severity of the disease. Further clinical studies are needed to confirm the use of NGAL as a biomarker for the detection and extent of CAD.

Urinary neutrophil gelatinase-associated lipocalin (NGAL) as an early marker of acute kidney injury in critically ill multiple trauma patients.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL), an iron-transporting protein rapidly accumulating in the kidney tubules and urine after nephrotoxic and ischemic insults, has been put forward as an early, sensitive, non-invasive biomarker for acute kidney injury (AKI). The aim of this study was to evaluate urinary NGAL levels as a predictor of early AKI (first 5 days after injury) in multi-trauma patients. METHODS: We studied multi-trauma adult patients admitted to the intensive care unit of a trauma hospital. Exclusion criteria were a) known cardiac or chronic kidney disease, and b) initial evaluation after more than 24 h had elapsed from injury. Urinary NGAL was measured using an ELISA technique upon admission and at 24 and 48 h. Presence of AKI was defined by the risk injury failure loss and end-stage kidney classification (RIFLE) criteria. Data are reported as median and interquartile range. RESULTS: A total of 31 patients (25 male, 6 female) were studied. NGAL levels at admission were significantly higher among patients who subsequently developed AKI [155.5 (50.5-205.9) ng/mL vs. 8.0 (5.7-17.7) ng/mL, p=0.0000] and these higher levels persisted over the following 2 days. On the basis of receiver-operating characteristic analysis both NGAL and serum creatinine baseline measurements could predict AKI [area under the curve (95% confidence interval) 0.977 (0.823-0.980) and 0.789 (0.556-0.906), respectively], but the area under the curve for NGAL was significantly larger (p=0.024). A cut-off point >25 ng/mL for NGAL had a sensitivity of 0.91 and specificity of 0.95 in predicting AKI. CONCLUSIONS: Urinary NGAL can be used from the 1st day of injury as a reliable predictor of early AKI in multi-trauma patients.

Does diagnostic coronary angiography induce significant coronary microembolization in stable, ischemic patients? A prospective study.

BACKGROUND: Although microembolization during percutaneous coronary interventions is a frequent event, the extent of possible microembolization during diagnostic coronary angiography is unknown. The aim of the study was to investigate whether diagnostic coronary angiography results in coronary microembolization and consequent subtle, subclinical myocardial necrosis with enzyme elevations. METHODS: Fifty-three consecutive patients underwent diagnostic coronary angiography due to inducible ischemia. Creatine kinase MB isoenzyme (CK MB) and cardiac troponin I (cTnI) were used as sensitive surrogate markers of myocardial necrosis. Serial measurements, before, and 6 and 24 hours following a diagnostic procedure, were performed. RESULTS: Baseline cTnI was below the limits of detection in all patients (<0.20 ng/mL), except for one patient with 1.31 ng/mL. Baseline median CK-MB was 1.05 ng/mL (interquartile range, 0.80-1.56 ng/mL) (Fig. 1). Both at 6 and 24 hours, no patients had any increase in cTnI, with the exception of a minor increase to 0.22 ng/mL at 24 hours in one patient. At 6 hours, 25 patients had decreases in CK MB, while 22 had increases (exact P = 0.77). At 24 hours, 26 patients had decreases in CK MB and 19 patients had increases. CONCLUSIONS: Detectable embolization with subsequent subclinical myonecrosis is an unlikely event.