Reference Values In Healthy Subjects Research Articles

The Non-Invasive Ultrasound-Based Assessment of Liver Viscosity in a Healthy Cohort.

Liver fibrosis is the most significant prognostic factor in chronic liver disease (CLD). Clinical practice guidelines recommend the use of non-invasive techniques, such as two-dimensional shear-wave elastography (2D-SWE), to assess liver stiffness as a marker of fibrosis. Several other factors influence liver stiffness in addition to liver fibrosis. It is presumed that changes due to necro-inflammation modify the propagation of shear waves (dispersion). Therefore, new imaging techniques that investigate the dispersion properties of shear waves have been developed, which can serve as an indirect method of measuring liver viscosity (Vi PLUS). Defining the reference values in healthy subjects among different age groups and genders and analyzing the factors that influence these values is essential. However, published data on liver viscosity are still limited. This is the first study that aimed to assess the normal range of liver viscosity values in subjects with healthy livers and analyze the factors that influence them. One hundred and thirty-one consecutive subjects with healthy livers were enrolled in this prospective study. The results showed that Vi PLUS is a highly feasible method. Liver stiffness, age and BMI influenced the liver viscosity values. The mean liver viscosity by Vi PLUS in subjects with healthy livers was 1.59 Pa·s.

Comparison of Kit-Based Metabolomics with Other Methodologies in a Large Cohort, towards Establishing Reference Values.

Metabolic profiling is an omics approach that can be used to observe phenotypic changes, making it particularly attractive for biomarker discovery. Although several candidate metabolites biomarkers for disease expression have been identified in recent clinical studies, the reference values of healthy subjects have not been established. In particular, the accuracy of concentrations measured by mass spectrometry (MS) is unclear. Therefore, comprehensive metabolic profiling in large-scale cohorts by MS to create a database with reference ranges is essential for evaluating the quality of the discovered biomarkers. In this study, we tested 8700 plasma samples by commercial kit-based metabolomics and separated them into two groups of 6159 and 2541 analyses based on the different ultra-high-performance tandem mass spectrometry (UHPLC-MS/MS) systems. We evaluated the quality of the quantified values of the detected metabolites from the reference materials in the group of 2541 compared with the quantified values from other platforms, such as nuclear magnetic resonance (NMR), supercritical fluid chromatography tandem mass spectrometry (SFC-MS/MS) and UHPLC-Fourier transform mass spectrometry (FTMS). The values of the amino acids were highly correlated with the NMR results, and lipid species such as phosphatidylcholines and ceramides showed good correlation, while the values of triglycerides and cholesterol esters correlated less to the lipidomics analyses performed using SFC-MS/MS and UHPLC-FTMS. The evaluation of the quantified values by MS-based techniques is essential for metabolic profiling in a large-scale cohort.

Clinical Features and Hearing Outcomes of Sudden Sensorineural Hearing Loss in Diabetic Patients.

Background and ObjectivesThis study aimed to evaluate the clinical features and the clinical factors associated with prognosis of sudden sensorineural hearing loss (SSNHL) in diabetic patients.Subjects and MethodsForty-nine diabetic with unilateral SSNHL were retrospectively included. All patients received systemic high dose steroid therapy within one month after onset and had more than one month of follow-up audiogram. The basic characteristics of the patients, initial and follow-up audiograms, laboratory data, and methods of steroid treatment were collected.ResultsCompared to reference values in healthy subjects, 79%, 55%, and 45% of the patients had higher values of mean neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR), respectively. Older patients had significantly less degree of hearing loss, but they also had significantly worse hearing thresholds in the unaffected ear. After steroid treatment, less than half patients (47%) showed hearing recovery. Simultaneous intratympanic dexamethasone (ITD) injections with systemic steroid did not confer an additional hearing gain or an earlier recovery rate in diabetic patients with SSNHL. In the multivariate analysis, initial hearing thresholds of affected ear and timing of steroid treatment were significantly associated with hearing prognosis in diabetic patients with SSNHL.ConclusionsDiabetic patients with SSNHL tended to have increased NLR, LMR, and PLR, which are reported to be associated with microvascular angiopathy. Simultaneous ITD injections to improve hearing recovery in diabetic patients with SSNHL seems unnecessary.

P737 Left ventricular hemodynamic forces: towards establishing reference values for healthy adults

Abstract Introduction Left ventricular hemodynamic forces (LV-HDF) have been recently demonstrated to be promising markers of sub-clinical dysfunction and potential predictors of disease outcome. However, there is a lack of reference values in healthy subjects. Knowledge of physiologic ranges is mandatory towards the use of LV-HDF-based indices for disease assessment in future clinical applications. Purpose Aim of the current study is to define the normal reference values for LV-HDF parameters in a large cohort of healthy adults. Here we present preliminary results for the initial set of enrolled subjects. Methods We enrolled 82 healthy subjects [mean age 44 ± 13.2 years (range 18-88), 41 men]. All participants underwent standard transthoracic echocardiography (TTE) examination, as recommended by current guidelines, including apical two-, three- and four-chamber windows, acquired at a frame rate above 40 Hz. These were then analyzed by tri-plane tissue tracking, measuring LV volume and LV ejection fraction (EF) as reference parameters. The same tracking method was used to evaluate the global hemodynamic force by a novel mathematical calculation technique applied to the three-dimensional endocardial contour. Physical-based LV-HDF parameters were then extracted for clinical application; these included the amplitude (root mean square) of the longitudinal and transversal force components (FL and FT) and their alignment angle relative to the LV axis. Parameters were computed as average over the whole cardiac cycle as well as limited to the systolic phase. Forces were normalized with LV volume to reduce variability with LV dimension, and divided by specific weight to yield a dimensionless measure. Results Mean EF was 63 ± 9%. Whole cycle LV-HDF parameters were: FL = 16.0 ± 5.6%, FT = 2.3 ± 0.8%, with significant longitudinal alignment FT/FL = 0.15 ± 0.04, angle = 13.0°±3.1°. Systolic HDF parameters were: FL = 22.7 ± 8.2%, FT = 2.9 ± 1.1%, with longitudinal alignment FT/FL = 0.13 ± 0.04, angle = 11.2°±3.1°. Importantly, dimensionless physical-based LV-HDF parameters showed no significant variation with age, gender or BSA. Conclusions We report the physiologic range of LV-HDF parameters measured by TTE. Knowledge of age- and gender-specific reference values, for a combination of standard, mechanical and hemodynamic indices, can improve the global assessment of the LV function and may help to detect sub-clinical stages of LV dysfunction.

Reference values for hand muscle strength evaluation methods in healthy young adults.

This study determined the hand muscle strength parameters and reference values in healthy subjects using the Nicholas Manual Muscle Tester (NMMT) and Manual Muscle Test (MMT) and compared these methods. The study was carried out with 200 (102 males, 98 females) healthy adults aged between 18-25 years. Muscle strength evaluations of the hand were performed to determine hand motor ability using both NMMT and MMT. The mean values of age, weight, height and body mass index (BMI) were 19.48 ± 0.95 years, 60.66 ± 8.82 kg, 165.30 ± 7.95 cm and 22.14 ± 2.25 kg/m2, respectively, in females, whereas the same values were found as 20.40 ± 1.34years, 72.53 ± 9.45 kg, 176.20 ± 6.29 cm and 23.25 ± 2.90 kg/m2, respectively, in males. There was a statistically significant difference in all demographic data between genders (p< 0.05). Furthermore, correlation coefficient in NMMT was found to be between 0.503 and 0.954. However, there was no correlation between the MMT and NMMT results. The observations presented need to be taken into consideration for evaluate musculoskeletal problems and also can be used as reference values for evaluating treatment outcomes.

Evaluation of Baseline Hematologic Parameters of Steady State Sickle Cell Disease Patients at The Chantal Biya’s Foundation, Yaounde- Cameroon

Introduction&#x0D; Sickle cell disease is a genetic abnormality involving the hemoglobin. Although it is primarily a red blood cell disorder, the white blood cells and platelets are also affected by the mutation. The consequence hemoglobin S causing polymerization of hemoglobin, results in hemolysis and anemia. This study aims to provide baseline hematologic parameters in steady state sickle cell disease patients compared with the reference values of normal healthy subjects used at the Chantal Biya Foundation (CBF), in order to monitor other sicklers in Cameroon.&#x0D; Methodology&#x0D; A comparative analysis of sickle cell hematologic parameters with control hematologic parameters of normal healthy subjects (reference values of healthy subjects used at the Chantal Biya Foundation) was carried out.&#x0D; Results&#x0D; A total of 62 sickle cell disease patients in steady state who complied with the selection criteria were recruited. Of the 62, 29 were females and 33 were males. The age range was from 1 year to 19 years and an average age of 6 ± 4.19 SD. Results from sickle cell patients showed an increase in white blood cells (WBCs), neutrophils and lymphocytes and a great decrease in the mean values of hematocrit Hct. as well as RBC indices, but no great or slight difference in the values of basophils compared with the reference values of normal healthy subjects in the CBF Yaoundé, 2015.&#x0D; Conclusion&#x0D; Sickle cell disease patients in steady state have lower values of red cells parameters, but higher values of white cells and platelets count when compared with the reference values of normal healthy subjects used at the Chantal Biya Foundation.

Younger age and hamstring tendon graft are associated with higher IKDC 2000 and KOOS scores during the first year after ACL reconstruction.

Although reference values in healthy subjects have been published for both the International Knee Documentation Committee 2000 subjective knee form (IKDC 2000) and the Knee injury and Osteoarthritis Outcome Score (KOOS), data obtained during the first year after anterior cruciate ligament reconstruction (ACL-R) are sparse. The aim was to establish patient reference values for both questionnaires at different time points and depending on nine individual patient characteristics during the first year after ACL-R. Prospectively recorded data from a hospital-based registry were retrospectively extracted from the database. IKDC 2000 and KOOS questionnaires were self-administered pre-operatively and 6weeks, 3months, and 6 and 12months following primary ACL-R. Score values were compared according to nine individual patient criteria: gender, age, body mass index, level of activity, involvement in competition, previous contralateral knee injury and/or surgery, graft type, meniscal repair and/or cartilage lesions. The feature which had a significant and consistent impact on the outcomes was considered as main reference. Two-hundred and nighty-eight patients met the inclusion criteria. Overall, the score values increased over time after ACL-R. At 12months, they were significantly greater than at any other time point (p < 0.05). The main individual feature influencing the IKDC 2000 score was age. Patients below 30years of age had up to 9 points higher IKDC 2000 score values at all time points (p < 0.05). The main individual characteristic influencing the KOOS score was graft type. Patients with hamstring tendon grafts (STGR) had up to 15 points higher KOOS score values than patients with bone-patellar tendon-bone (BPTB) grafts during the first months after ACL-R (p < 0.05). At 12months, no differences in KOOS score values could be identified anymore. Younger age (< 30years) and STGR grafts were related to higher IKDC 2000 and KOOS score values within the first year after primary ACL-R. The patient reference values adjusted to age and graft provided in this study may help to identify patients with lower outcomes within the first year after ACL-R. Level III.

P 45 Ultrasonography of facial muscles in patients with Parkinson’s disease

Purpose Parkinson’s disease is one of the commonest movement disorders, characterized by bradykinesia, rigor or tremor. While a standardized protocol for sonography of the mimic musculature is already applied in patients with facial palsy, it was not known, whether the protocol can also be used for objective analysis of facial muscles in patients with Parkinson’s disease. Material & methods Using a eZono4000, eZono, Germany, with linear probe (L3-12), bilateral scans of seven facial muscles and two masticatory muscles were performed in 38 patients with Parkinson’s disease (18 women; Hoehn & Yahr 1–5; mean/SD: 3.01/1.07; mean UPDRS III 32.47/14.78). The scans were based on the same standardized examination protocol ( Volk, 2014 ). Following muscles were scanned at rest and at maximal contraction: frontalis, orbicularis oculi, zygomaticus major, orbicularis oris, depressor anguli oris, depressor labii inferioris, mentalis, and masseter and temporalis muscle. The muscles cross-sectional areas as well as the biggest longitudinal- and cross-diameter at rest and maximal contraction were manually segmented. The results were compared with reference values of healthy subjects and correlated with the clinical data describing the severity of the Parkinson’s disease (UPDRS III; single items: finger tapping/facial expression). Results In patients with Parkinson’s disease nearly every acquired muscle cross-section and also the ability to contract were significantly ( p r = −0,296/ p = 0,080) and to the item facial expression ( r = −0.345/ p = 0.034). Due to the explorative character of the study, methods to counteract the problem of multiple comparisons were not applied. Conclusion The ultrasonography can be applied to describe changes in facial muscles characteristic for Parkinson’s disease. Especially the impact of the bradykinesia expressed as the reduced ability to contract can be objectively assessed. After this proof-of principle investigation further longitudinal studies in larger cohorts are necessary to evaluate the dependence between clinical features and ultrasonography.

Clinical, radiographic and biochemical characteristics of adult hypophosphatasia.

Hypophosphatasia (HPP) is a rare disorder with a wide range of clinical manifestations. A reduced enzymatic activity of alkaline phosphatase (ALP) is the key marker of the disease, causing an accumulation of ALP substrates such as pyridoxal-5-phosphate (PLP). The purpose of this retrospective study was to further characterize adult onset HPP. We assessed clinical, radiographic and laboratory characteristics of 38 adult patients with HPP. Diagnosis of HPP was established by the combination of low-serum ALP, raised PLP levels and typical symptoms and was genetically confirmed in 32 patients. Dual-energy X-ray absorptiometry (DXA) and laboratory data were available in most patients. High-resolution peripheral quantitative computed tomography (HR-pQCT) was performed in 14 patients. Clinical characteristics included a wide spectrum of symptoms. A history of fracture was present in 15 patients (39%). Twenty-one patients (55%) complained about recurring headaches, 23 patients (61%) had recurring muscle pain, 4 patients (11%) suffered from severe muscle weakness and 18 patients (47%) showed dental abnormalities. Z-scores assessed by DXA were only slightly reduced in most adult HPP patients. HR-pQCT of 14 patients showed microstructural changes of trabecular and cortical bone compared to reference values of healthy subjects. The occurrence of fractures and multiple symptoms (>2 typical HPP symptoms) were associated with significantly elevated levels of PLP. Adult HPP presents with a wide range of clinical symptoms and is not associated with low bone mass in general. PLP seems to be a good marker for disease severity in adult patients as its level is correlated with the occurrence of fractures and number of symptoms.

Validation of the Exhaled Breath Temperature Measure: Reference Values in Healthy Subjects

Exhaled breath temperature (EBT) is a new noninvasive method for the study of inflammatory respiratory diseases with a potential to reach clinical practice. However, few studies are available regarding the validation of this method, and they were mainly derived from small, pediatric populations; thus, the range of normal values is not well established. The aim of this study was to measure EBT values in an Italian population of 298 subjects (mean age, 45.2 ± 15.5 years; 143 male subjects; FEV1, 97.2%± 5.8%; FVC, 98.4%± 3.9%) selected from 867 adult volunteers to define reference values in healthy subjects and to analyze the influence of individual and external variables on this parameter. EBT was measured with an X-halo PRO device to different ambient temperature ranging from 0°C to 38°C. We report reference values of EBT in healthy white subjects who had never smoked. EBT values were strongly influenced by the external temperature and to a lesser extent according to sex. In a large population of healthy subjects who never smoked, these data provide reference values for measuring EBT as a basis for future studies. Our results are contribute to the promotion of EBT from "bench" to "bedside."

Normative Values for Electrochemical Skin Conductances and Impact of Ethnicity on Quantitative Assessment of Sudomotor Function.

Sudomotor dysfunction is one of the earliest pathophysiologic abnormalities in diabetes. Sudoscan™ (Impeto Medical, Paris, France) was developed as a noninvasive, rapid, and quantitative assessment of sudomotor function and has been shown to be sensitive in the detection of neuropathy. This global collaborative analysis aimed to establish reference values in healthy subjects of different ethnic groups, age, and gender, to define factors potentially affecting results, and to provide standardization of the methodology. Data from 1,350 generally healthy study participants who underwent sudomotor function testing were collected and analyzed. The relationship between age, height, weight, gender, glycemic and lipid profiles, ethnicity, and hand and foot electrochemical skin conductance (ESC) was assessed among subgroups of participants. Lower mean hands and feet ESC values were observed in African American, Indian, and Chinese subjects (P < 0.0001). No participant discomfort or safety concern was reported in 1,376 tests. No significant difference in ESC was observed between women and men at the hands (75 [57-87] vs. 76 [56-89] μS; P = 0.35) or feet (83.5 [71-90] vs. 82.5 [70-91] μS; P = 0.12). The coefficient of correlation between right and left side ESC was r = 0.96, P < 0.0001 for hands and r = 0.97, P < 0.0001 for feet. A significant but weak correlation was observed between ESC and age: for hands, r = -0.17, P < 0.0001; for feet, r = -0.19, P < 0.0001. A normative reference range was established in whites showing that there was no effect of sex or body mass index and a slight decrease in ESC with age. Ethnicity influenced ESC scores, but additional studies are necessary to validate this effect and determine its mechanism and impact on nerve function.

WS21.10 Respiratory muscle endurance training with normocapnic hyperpnea in patients with cystic fibrosis. A randomized controlled study

Objectives The aim of our study was to investigate the effects of an eight weeks respiratory muscle endurance training with normocapnic hyperpnea (RMNH) in a group of patients with CF on the following outcomes: respiratory muscles endurance, exercise tolerance (six minutes walk test), health-related quality of life (CFQ-R) and lung function (FVC, FEV1, MVV, MIP, MEP). Methods Ten patients with CF (4F), age 21–40 were included, randomly assigned to RMNH program (RMNH and standard chest physiotherapy) or control group (standard chest physiotherapy alone). Respiratory muscle endurance, six minutes walk distance, health-related quality of life as measured by the CFQ-R questionnaire and lung function (FVC, FEV1, MIP, MEP) were measured before and after RMNH. Respiratory endurance test was performed using the SpiroTiger® device: the endurance time was calculated asking the patient to maintain a target VE of 70% of the 12-s maximum voluntary ventilation (MVV) until he/she could no longer maintain the target VE. Reference values in healthy subjects have been used to set up the device. The patients underwent four 15-minute daily training sessions every week, till the end of the study. Results At the end of the study we observed a statistically significant difference between the two groups in the 6MWT walk distance: study group 665±30 m; control group 569±30 m (mean±SD) (p Conclusion The RMNH leads to a significant increase in exercise tolerance. However, other clinical relevant outcomes such as respiratory muscles endurance, lung function and health-related quality of life were unaffected by RMNH.

How fit are children and adolescents with haemophilia in Germany? Results of a prospective study assessing the sport-specific motor performance by means of modern test procedures of sports science.

There are a lot of publications on the physical fitness of patients with haemophilia (PWH), however, most studies only reflect individual sport-specific motor capacities or focus on a single fitness ability. They involve small patient populations. In this respect principal objective of this study was to compare the physical fitness in all respects and the body composition of young PWH to healthy peers based on the most valid data we could get. Twenty-one German haemophilia treatment centres were visited from 2002 to 2009. PWH between 8 and 25years were included. They performed a five-stage fitness test covering the sport-specific motor capacities for coordination, measured by one leg stand, strength, aerobic fitness and mobility as well as body composition. The patients' results were compared with age- and gender-specific reference values of healthy subjects. Two hundred and eighty-five PWH (mean age 13.2±4.5years, 164 PWH with severe disease) were included prospectively in the study. PWH are significantly below the reference values of healthy subjects in the one-leg stand test, the mobility of the lower extremity, the strength ratio of chest and back muscles and the endurance test. In body composition, the back strength and the mobility of the upper extremity PWH are significantly above the reference values. There are no significant differences in abdominal strength. In conclusion we found specific differences in different fitness abilities between PWH and healthy subjects. Knowing this, we are able to work out exercise programmes to compensate the diminished fitness abilities for our PWH.

Identification of cardiac repercussions after intense and prolonged concentric isokinetic exercise in young sedentary people.

Cardiopathies are the world's leading cause of mortality and morbidity. Although rare, cardiovascular accidents can occur during intense and infrequent sporting activity, particularly among those who are unaware of their heart condition. The development of cardiospecific biochemical markers has led to a reconsideration of the role of biology in the diagnosis of cardiovascular illnesses. The aim of this study therefore was, through the use of cardiac biomarker assays, to highlight the impact of sustained physical effort in the form of intense and prolonged concentric isokinetic exercise and to research potential cardiovascular risks. Eighteen subjects participated in a maximal concentric isokinetic exercise involving 30 knee flexion-extensions for each leg. Five blood tests were taken to study the kinetics of the cardiac biomarkers. Haemodynamic parameters were measured continuously using a Portapres, and respiratory parameters were measured using a Sensormedics Vmax 29C. The results showed significant increases in the creatine kinase, myoglobin, homocysteine and haemoglobin cardiac markers. Evolutionary trends were also observed for the following biomarkers: NT-proBNP, myeloperoxydase and C-reactive protein. All the physiological parameters measured presented statistically significant changes. Isokinetic effort leads to the release of cardiac markers in the blood, but these do not exceed the reference values in healthy subjects. Maximal concentric isokinetic exercise does not, therefore, lead to an increased risk of cardiovascular pathologies.

C-type natriuretic peptide plasma levels are reduced in obese adolescents

The high prevalence of obesity in children may increase the magnitude of lifetime risk of cardiovascular disease (CD). At present, explicit data for recommending biomarkers as routine pre-clinical markers of CD in children are lacking. C-type natriuretic peptide (CNP) is assuming increasing importance in CD; in adults with heart failure, its plasma levels are related to clinical and functional disease severity. We have previously reported five different reference intervals for blood CNP as a function of age in healthy children; however, data on plasma CNP levels in obese children are still lacking. Aim of this study was to assess CNP levels in obese adolescents and verify whether they differ from healthy subjects. Plasma CNP was measured in 29 obese adolescents (age: 11.8±0.4 years; BMI: 29.8±0.82) by radioimmunoassay and compared with the reference values of healthy subjects. BNP was also measured. Both plasma CNP and BNP levels were significantly lower in the obese adolescents compared to the appropriate reference values (CNP: 3.4±0.2 vs 13.6±2.3pg/ml, p<0.0001; BNP: 18.8±2.6 vs 36.9±5.5pg/ml, p=0.003). There was no significant difference between CNP values in males and females. As reported in adults, we observed lower plasma CNP and BNP levels in obese children, suggesting a defective natriuretic peptide system in these patients. An altered regulation of production, clearance and function of natriuretic peptides, already operating in obese adolescents, may possibly contribute to the future development of CD. Thus, the availability of drugs promoting the action of natriuretic peptides may represent an attractive therapeutic option to prevent CD.

Values for αβ and γδ T‐lymphocytes and CD4+, CD8+, and CD56+ subsets in healthy adult subjects: Assessment by age and gender

Normal reference values in healthy subjects for T-lymphocytes for both types of receptors, αβ and γδ, and their subsets are yet to be defined. The aim of this study was to measure peripheral blood αβ and γδ total T-lymphocytes and their subsets in a population of healthy subjects, in order to obtain valid reference values for studies in human pathology. We studied a total of 157 healthy subjects, 78 men and 79 women, establishing their levels of CD3+, CD4+, CD8+, CD56+, αβCD3+, αβCD3+CD4+, αβCD3+CD8+, αβCD3+CD56+, γδCD3+, γδCD3+CD4-CD8-, γδCD3+CD8+, and γδCD3+CD56+ T-cells by flow cytometry. The T-cell subsets were compared for different age and gender groups. A significant decrease in CD3+, CD3+CD4+, CD3+CD4+ αβ, and CD3+ γδ T-cells was observed in elderly subjects. CD3+, CD3+ αβ, and CD3+CD4+ αβ T-cells increased in women, while CD3+CD56+ αβ T-cells increased in men. CONCLUSIONS.: These reference values could be useful in further research studies for assessing changes that occur in the different αβ and γδ T subsets in human pathology.

A meta-analysis of left ventricular dyssynchrony assessment and prediction of response to cardiac resynchronization therapy by three-dimensional echocardiography

In a time of controversy regarding the use of echocardiography for assessment of left ventricular (LV) dyssynchrony and prediction of response to cardiac resynchronization therapy (CRT), this meta-analysis aimed to evaluate the feasibility and reliability of LV dyssynchrony assessment by three-dimensional echocardiography (3DE), determine clinically useful reference values in healthy subjects and heart failure patients, and examine the accuracy of 3DE to predict response to CRT. A total of 73 studies that evaluated the assessment of LV dyssynchrony by 3DE were eligible. The systolic dyssynchrony index (SDI) for 16 segments, being the predominant 3DE dyssynchrony parameter, was used for data pooling. Results demonstrated that LV dyssynchrony assessment by 3DE is feasible in 94% of studied subjects [95% confidence interval (CI): 92-95%)]. Pooled estimates of intraclass correlation coefficients (ICC) and limits of agreement (LoA) demonstrated that SDI has good interobserver (ICC: 0.92, LoA: 4.07%) and intraobserver reliability (ICC: 0.95, LoA: 2.10%). Reference values of SDI in healthy subjects, heart failure patients in general, and patients eligible for CRT were 2.7 ± 0.9%, 9.8 ± 3.9%, and 10.7 ± 3.6%, respectively. Meta-regression analysis demonstrated that reference values of SDI in healthy subjects significantly differed between different software [1.80% (95% CI: 0.55-3.05%), P< 0.001]. In patients eligible for CRT, SDI had good accuracy to predict treatment response with a weighted mean cut-off value of 9.8% and pooled estimates for sensitivity and specificity of 93% (95% CI: 89-97%) and 75% (95% CI: 58-93%), respectively. 3DE is a feasible and reliable tool for assessment of LV dyssynchrony and may have additional value to current selection criteria for accurate prediction of response to CRT.

Unsupervised multiparametric classification of dynamic susceptibility contrast imaging: Study of the healthy brain

Characterization and quantification of magnetic resonance perfusion images is important for clinical interpretation, though this calls for a reproducible and accurate method of analysis and a robust healthy reference. The few studies which have examined the perfusion of the healthy brain using dynamic susceptibility contrast (DSC) imaging were largely limited to manual definition of the regions of interest (ROI) and results were dependent on the location of the ROI. The current study aimed to develop a methodology for DSC data analysis and to obtain reference values of healthy subjects. Twenty three healthy volunteers underwent DSC. An unsupervised multiparametric clustering method was applied to four perfusion parameters. Three clusters were defined and identified as: dura–blood-vessels, gray matter and white matter and their vascular characteristics were obtained. Additionally, regional perfusion differences were studied and revealed a prolonged mean transient time and a trend for higher vascularity in the posterior compared with the anterior and middle cerebral vascular territories. While additional studies are required to confirm our findings, this result may have important clinical implications. The proposed unsupervised multiparametric method enabled accurate tissue differentiation, is easy replicable and has a wide range of applications in both pathological and healthy brains.

Impulse oscillometry in preschool children and association with body mass index

The use of the impulse oscillometry system (IOS) allows differentiated lung function testing with a minimum of cooperation at normal tidal breathing. The aim of this cross-sectional study was to assess the association of body mass (overweight and obese) with oscillometric parameters in preschool children. A preschool medical check of 518 children (age 6.01 ± 0.25 years) included IOS recordings of airway resistance and lung reactance (MasterScreen IOS, CareFusion, Höchberg, Germany). Measured values of respiratory resistance (R5) and reactance (X5) at 5 Hz were correlated with BMI. In addition, data were compared with recently published reference equations. In this young age group of 241 boys and 277 girls there was no significant association between oscillometric parameters and BMI. When compared with current IOS reference values of healthy subjects the relationship of R5 (109 ± 25%) and X5 (105.5 ± 35%) suggested mildly elevated peripheral resistance in this unselected group of preschool children. IOS is ideally suited to obtain measurements of respiratory function in preschool children. At the age of 6 years, standard oscillometric values do not indicate impaired respiratory function associated with increased BMI.

Determination of ultrafiltrable and exchangeable copper in plasma: stability and reference values in healthy subjects

The knowledge of copper (Cu) distribution in blood contributes to a better understanding of copper metabolism and to a better approach and follow up of related diseases such as Wilson's disease (WD). Many tests can be used to investigate patients who may have WD but they show many drawbacks and do not allow real patient monitoring. Knowing that the Cu overload can result from the free and easily exchangeable form of copper in plasma, a two-step method (ultrafiltration-determination by ETAAS) was carried out to determine these two fractions. The ultrafiltration procedure and the instrumental determination showed good repeatability, and a very low limit of detection was obtained (0.7 nmol/L). In vitro stability of both ultrafiltrable copper (CuUF) and exchangeable copper (CuEXC) was studied. Plasma was ultrafiltered in 44 presumably healthy subjects to determine CuUF and CuEXC and to set reference values ranges. The method was applied on a few patients showing good correlation between both parameters and the clinical and biological features of the patients.