Prognostic value of fractional flow reserve: linking physiologic severity to clinical outcomes.

BACKGROUND: Fractional flow reserve (FFR) has become an established tool for guiding treatment, but its graded relationship to clinical outcomes as modulated by medical therapy versus revascularization remains unclear. OBJECTIVES: The study hypothesized that FFR displays a continuous relationship between its numeric value and prognosis, such that lower FFR values confer a higher risk and therefore receive larger absolute benefits from revascularization. METHODS: Meta-analysis of study- and patient-level data investigated prognosis after FFR measurement. An interaction term between FFR and revascularization status allowed for an outcomes-based threshold. RESULTS: A total of 9,173 (study-level) and 6,961 (patient-level) lesions were included with a median follow-up of 16 and 14 months, respectively. Clinical events increased as FFR decreased, and revascularization showed larger net benefit for lower baseline FFR values. Outcomes-derived FFR thresholds generally occurred around the range 0.75 to 0.80, although limited due to confounding by indication. FFR measured immediately after stenting also showed an inverse relationship with prognosis (hazard ratio: 0.86, 95% confidence interval: 0.80 to 0.93; p < 0.001). An FFR-assisted strategy led to revascularization roughly half as often as an anatomy-based strategy, but with 20% fewer adverse events and 10% better angina relief. CONCLUSIONS: FFR demonstrates a continuous and independent relationship with subsequent outcomes, modulated by medical therapy versus revascularization. Lesions with lower FFR values receive larger absolute benefits from revascularization. Measurement of FFR immediately after stenting also shows an inverse gradient of risk, likely from residual diffuse disease. An FFR-guided revascularization strategy significantly reduces events and increases freedom from angina with fewer procedures than an anatomy-based strategy.

Statistically significant changes of antimüllerian hormone and inhibin levels during the physiologic menstrual cycle in reproductive age women.

OBJECTIVE: To define the dynamics of antimüllerian hormone (AMH) and inhibins during the physiologic menstrual cycle. DESIGN: Longitudinal study. SETTING: University hospital. PATIENT(S): 36 young, healthy, normal weight Caucasian women without medication. INTERVENTION(S): Normal ovulatory menstrual cycles were evaluated by regular blood sampling taken every other day and periovulatory every day. MAIN OUTCOME MEASURE(S): Serum concentrations of AMH, inhibin A and B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin, estradiol, progesterone, and free testosterone were measured in all blood samples. RESULT(S): Median AMH levels are statistically significantly higher in the late follicular compared with ovulation or the early luteal phase. There are statistically significant correlations between both AMH and FSH, and AMH and free testosterone in all cycle phases. Inhibin A increases strongly in the late follicular phase and peaks at day LH + 4. Inhibin B shows a broad midfollicular and a sharp early luteal peak, the difference being statistically significant between day LH + 4 and the earlier time points and between day LH + 2 and day LH. Although there is a negative association between inhibin A or B and the body mass index (BMI), there is no correlation between AMH and the BMI. CONCLUSION(S): Levels of AMH show a statistically significant change during the menstrual cycle and may influence the circulating gonadotropin and steroid hormone levels.

Heritability, determinants and reference values of renal length: a family-based population study.

OBJECTIVES: In this population-based study, reference values were generated for renal length, and the heritability and factors associated with kidney length were assessed. METHODS: Anthropometric parameters and renal ultrasound measurements were assessed in randomly selected nuclear families of European ancestry (Switzerland). The adjusted narrow sense heritability of kidney size parameters was estimated by maximum likelihood assuming multivariate normality after power transformation. Gender-specific reference centiles were generated for renal length according to body height in the subset of non-diabetic non-obese participants with normal renal function. RESULTS: We included 374 men and 419 women (mean ± SD, age 47 ± 18 and 48 ± 17 years, BMI 26.2 ± 4 and 24.5 ± 5 kg/m(2), respectively) from 205 families. Renal length was 11.4 ± 0.8 cm in men and 10.7 ± 0.8 cm in women; there was no difference between right and left renal length. Body height, weight and estimated glomerular filtration rate (eGFR) were positively associated with renal length, kidney function negatively, age quadratically, whereas gender and hypertension were not. The adjusted heritability estimates of renal length and volume were 47.3 ± 8.5 % and 45.5 ± 8.8 %, respectively (P < 0.001). CONCLUSION: The significant heritability of renal length and volume highlights the familial aggregation of this trait, independently of age and body size. Population-based references for renal length provide a useful guide for clinicians. KEY POINTS: • Renal length and volume are heritable traits, independent of age and size. • Based on a European population, gender-specific reference values/percentiles are provided for renal length. • Renal length correlates positively with body length and weight. • There was no difference between right and left renal lengths in this study. • This negates general teaching that the left kidney is larger and longer.

Endogenous steroid profiling in the athlete biological passport.

The Athlete Biological Passport (ABP) is an individual electronic document that collects data regarding a specific athlete that is useful in differentiating between natural physiologic variations of selected biomarkers and deviations caused by artificial manipulations. A subsidiary of the endocrine module of the ABP, that which here is called Athlete Steroidal Passport (ASP), collects data on markers of an altered metabolism of endogenous steroidal hormones measured in urine samples. The ASP aims to identify not only doping with anabolic-androgenic steroids, but also most indirect steroid doping strategies such as doping with estrogen receptor antagonists and aromatase inhibitors. Development of specific markers of steroid doping, use of the athlete's previous measurements to define individual limits, with the athlete becoming his or her own reference, the inclusion of heterogeneous factors such as the UDPglucuronosyltransferase B17 genotype of the athlete, the knowledge of potentially confounding effects such as heavy alcohol consumption, the development of an external quality control system to control analytical uncertainty, and finally the use of Bayesian inferential methods to evaluate the value of indirect evidence have made the ASP a valuable alternative to deter steroid doping in elite sports. The ASP can be used to target athletes for gas chromatography/combustion/ isotope ratio mass spectrometry (GC/C/IRMS) testing, to withdraw temporarily the athlete from competing when an abnormality has been detected, and ultimately to lead to an antidoping infraction if that abnormality cannot be explained by a medical condition. Although the ASP has been developed primarily to ensure fairness in elite sports, its application in endocrinology for clinical purposes is straightforward in an evidence-based medicine paradigm.

Blood pressure change and outcome in acute ischemic stroke: the impact of baseline values, previous hypertensive disease and previous antihypertensive treatment.

BACKGROUND: Management of blood pressure (BP) in acute ischemic stroke is controversial. The present study aims to explore the association between baseline BP levels and BP change and outcome in the overall stroke population and in specific subgroups with regard to the presence of arterial hypertensive disease and prior antihypertensive treatment. METHODS: All patients registered in the Acute STroke Registry and Analysis of Lausanne (ASTRAL) between 2003 and 2009 were analyzed. Unfavorable outcome was defined as modified Rankin score more than 2. A local polynomial surface algorithm was used to assess the effect of BP values on outcome in the overall population and in predefined subgroups. RESULTS: Up to a certain point, as initial BP was increasing, optimal outcome was seen with a progressively more substantial BP decrease over the next 24-48 h. Patients without hypertensive disease and an initially low BP seemed to benefit from an increase of BP. In patients with hypertensive disease, initial BP and its subsequent changes seemed to have less influence on clinical outcome. Patients who were previously treated with antihypertensives did not tolerate initially low BPs well. CONCLUSION: Optimal outcome in acute ischemic stroke may be determined not only by initial BP levels but also by the direction and magnitude of associated BP change over the first 24-48 h.

Pulse oximetry in pediatric intensive care: comparison with measured saturations and transcutaneous oxygen tension.

We evaluated a new pulse oximeter designed to monitor beat-to-beat arterial oxygen saturation (SaO2) and compared the monitored SaO2 with arterial samples measured by co-oximetry. In 40 critically ill children (112 data sets) with a mean age of 3.9 years (range 1 day to 19 years), SaO2 ranged from 57% to 100%, and PaO2 from 27 to 128 mm Hg, heart rates from 85 to 210 beats per minute, hematocrit from 20% to 67%, and fetal hemoglobin levels from 1.3% to 60%; peripheral temperatures varied between 26.5 degrees and 36.5 degrees C. Linear correlation analysis revealed a good agreement between simultaneous pulse oximeter values and both directly measured SaO2 (r = 0.95) and that calculated from measured arterial PaO2 (r = 0.95). The device detected several otherwise unrecognized drops in SaO2 but failed to function in four patients with poor peripheral perfusion secondary to low cardiac output. Simultaneous measurements with a tcPO2 electrode showed a similarly good correlation with PaO22 (r = 0.91), but the differences between the two measurements were much wider (mean 7.1 +/- 10.3 mm Hg, range -14 to +49 mm Hg) than the differences between pulse oximeter SaO2 and measured SaO2 (1.5% +/- 3.5%, range -7.5% to -9%) and were not predictable. We conclude that pulse oximetry is a reliable and accurate noninvasive device for measuring saturation, which because of its rapid response time may be an important advance in monitoring changes in oxygenation and guiding oxygen therapy.

Conclusions on the measurement of arterial wall thickness: anatomic, physiologic and methodologic considerations

AIM: To discuss the use of new ultrasonic techniques that make it possible to visualize elastic (carotid) and muscular (radial) capacitance arteries non-invasively. RESULTS OF DATA REVIEW: Measurements of carotid wall thickness and the detection of atheromas are related to arterial pressure, to other risk factors and to the risk of subsequent complications. The use of high-frequency ultrasound (7.5-10 MHz), measurements of far wall thicknesses in areas free of atheromas at end-diastole (by ECG gating or pressure waveform recording) and descriptions of the size and characteristics of atherosclerotic plaques allow a non-invasive assessment of vascular hypertrophy and atherosclerosis in hypertensive patients. CONCLUSIONS: Careful attention to methodologic and physiologic factors is needed to provide accurate information about the anatomy of the dynamically pulsating arterial tree.

Body mass index: comparing mean values and prevalence rates from telephone and examination surveys.

BACKGROUND: Cost effective means of assessing the levels of risk factors in the population have to be defined in order to monitor these factors over time and across populations. This study is aimed at analyzing the difference in population estimates of the mean levels of body mass index (BMI) and the prevalences of overweight, between health examination survey and telephone survey. METHODS: The study compares the results of two health surveys, one by telephone (N=820) and the other by physical examination (N=1318). The two surveys, based on independent random samples of the population, were carried out over the same period (1992-1993) in the same population (canton of Vaud, Switzerland). RESULTS: Overall participation rates were 67% and 53% for the health interview survey (HIS) and the health examination survey (HES) respectively. In the HIS, the reporting rate was over 98% for weight and height values. Self-reported weight was on average lower than measured weight, by 2.2 kg in men and 3.5 kg in women, while self-reported height was on average greater than measured height, by 1.2 cm in men and 1.9 cm in women. As a result, in comparison to HES, HIS led to substantially lower mean levels of BMI, and to a reduction of the prevalence rates of obesity (BMI>30 kg/m(2)) by more than a half. These differences are larger for women than for men. CONCLUSION: The two surveys were based on different sampling procedures. However, this difference in design is unlikely to explain the systematic bias observed between self-reported and measured values for height and weight. This bias entails the overall validity of BMI assessment from telephone surveys.

Continuous monitoring of liver oxygenation with near infrared spectroscopy during naso-gastric tube feeding in neonates.

Near infrared spectroscopy (NIRS) is a non-invasive method of estimating the haemoglobin concentration changes in certain tissues. It is frequently used to monitor oxygenation of the brain in neonates. At present it is not clear whether near infrared spectroscopy of other organs (e.g. the liver as a corresponding site in the splanchnic region, which reacts very sensitively to haemodynamic instability) provides reliable values on their tissue oxygenation. The aim of the study was to test near infrared spectroscopy by measuring known physiologic changes in tissue oxygenation of the liver in newborn infants during and after feeding via a naso-gastric tube. The test-retest variability of such measurements was also determined. On 28 occasions in 25 infants we measured the tissue oxygenation index (TOI) of the liver and the brain continuously before, during and 30 minutes after feeding via a gastric tube. Simultaneously we measured arterial oxygen saturation (SaO2), heart rate (HR) and mean arterial blood pressure (MAP). In 10 other newborn infants we performed a test-retest analysis of the liver tissue oxygenation index to estimate the variability in repeated intra-individual measurements. The tissue oxygenation index of the liver increased significantly from 56.7 +/- 7.5% before to 60.3 +/- 5.6% after feeding (p < 0.005), and remained unchanged for the next 30 minutes. The tissue oxygenation index of the brain (62.1 +/- 9.7%), SaO2 (94.4 +/- 7.1%), heart rate (145 +/- 17.3 min-1) and mean arterial blood pressure (52.8 +/- 10.2 mm Hg) did not change significantly. The test-retest variability for intra-individual measurements was 2.7 +/- 2.1%. After bolus feeding the tissue oxygenation index of the liver increased as expected. This indicates that near infrared spectroscopy is suitable for monitoring changes in tissue oxygenation of the liver in newborn infants.

Relation between intraoperative EMG values and final pedicle screw position as seen on CT images

Introduction: Intraoperative EMG based neurophysiological monitoring is increasingly used to assist pedicle screw insertion. We carried out a study comparing the final screw position in the pedicle measured on CT images in relation to its corresponding intraoperative muscle compound action potential (CMAP) values. Material and methods: A total of 189 screws were inserted in thoracolumbar spines of 31 patients during instrumented fusion under EMG control. An observer, blinded to the CMAP value, assessed the horizontal and vertical 'screw edge to pedicle edge' distance perpendicular to the longitudinal axis of the screw on reformatted CT reconstructions using OsiriX software. These distances were analysed with their corresponding CMAP values. Data from 62 thoracic and 127 lumbar screws were processed separately. Interobserver reliability of distance measurements was assessed. Results: No patient suffered neurological injury secondary to screw insertion. Distance measurements were reliable (paired t-test, P = 0.13/0.98 horizontal/vertical). Two screws had their position altered due to low CMAP values suggesting close proximity of nerve tissue. Seventy five percent of screws had CMAP results above 10mA and had an average distance of 0.35cm (SD 0.23) horizontally and 0.46cm (SD 0.26) vertically from the pedicle edge. Additional 12% had a distance from the edge of the pedicle less than 0mm indicating cortical breach but had CMAP values above 10mA. A poor correlation between CMAP values and screw position was found. Discussion: In this study CMAP values above 10mA indicated correct screw position in the majority of cases. The zone of 10-20mA CMAP carries highest risk of a misplaced screw despite high CMAP value (17% of screws this CMAP range). In order to improve accuracy of EMG predictive value further research is warranted including improvement of probing techniques.

What Kind of Justice Today ? Expectations Of 'Good Justice', Convergences And Divergences Between Managerial And Judicial Actors And How They Fit Within Management-Oriented Values

This research aims toward a better understanding of the organizational culture(s) of the judiciary in Switzerland by analysing what 'good justice' means nowadays in this country. It seeks to clarify whether, and to what extent, expectations of 'good justice' of judicial actors (judges without managerial experience) and of managerial actors (court managers) are similar and to describe possible managerial implications that may result from this. As judges are at the heart of the judicial organization and exert a strong influence on other groups of actors (Sullivan, Warren et al. 1994), the congruence of their expectations with those of court managers will be at the centre of the analysis. Additionally, referring to the conceptual worlds of Boltanski and Thévenaut (1991), we analyze how closely these expectations are to management-oriented values. We found that almost half of expectations are common to the two groups examined and the main quoted ones are compatible to new public management (NPM) concepts. On the other hand, those expectations shared exclusively by judges relate to the human side of justice, whereas those specific to court managers focus on the way justice functions.

Assessment of free-living physical activity in humans: an overview of currently available and proposed new measures.

The number of physical activity measures and indexes used in the human literature is large and may result in some difficulty for the average investigator to choose the most appropriate measure. Accordingly, this review is intended to provide information on the utility and limitations of the various measures. Its primary focus is the objective assessment of free-living physical activity in humans based on physiological and biomechanical methods. The physical activity measures have been classified into three categories: Measures based on energy expenditure or oxygen uptake, such as activity energy expenditure, activity-related time equivalent, physical activity level, physical activity ratio, metabolic equivalent, and a new index of potential interest, daytime physical activity level. Measures based on heart rate monitoring, such as net heart rate, physical activity ratio heart rate, physical activity level heart rate, activity-related time equivalent, and daytime physical activity level heart rate. Measures based on whole-body accelerometry (counts/U time). Quantification of the velocity and duration of displacement in outdoor conditions by satellites using the Differential Global Positioning System may constitute a surrogate for physical activity, because walking is the primary activity of man in free-living conditions. A general outline of the measures and indexes described above is presented in tabular form, along with their respective definition, usual applications, advantages, and shortcomings. A practical example is given with typical values in obese and non-obese subjects. The various factors to be considered in the selection of physical activity methods include experimental goals, sample size, budget, cultural and social/environmental factors, physical burden for the subject, and statistical factors, such as accuracy and precision. It is concluded that no single current technique is able to quantify all aspects of physical activity under free-living conditions, requiring the use of complementary methods. In the future, physical activity sensors, which are of low-cost, small-sized, and convenient for subjects, investigators, and clinicians, are needed to reliably monitor, during extended periods in free-living situations, small changes in movements and grade as well as duration and intensity of typical physical activities.

Ascending aorta measurements as assessed by ECG-gated multi-detector computed tomography : a pilot study to etablish normative values for transcatheters therapies

Rapport de synthèse : Mesures de l'aorte ascendante par scanner synchronisé au rythme cardiaque: une étude pilote pour établir des valeurs normatives dans le cadre des futures thérapies par transcathéter. Objectif : L'objectif de cette étude est d'établir les valeurs morphométriques normatives de l'aorte ascendante à l'aide de l'angiographie par scanner synchronisé au rythme cardiaque, afin d'aider au développement des futurs traitements par transcathéter. Matériels et méthodes : Chez soixante-dix-sept patients (âgé de 22 à 83 ans, âge moyen: 54,7 ans), une angiographie par scanner synchronisé au rythme cardiaque a été réalisée pour évaluation des vaisseaux coronaires. Les examens ont été revus afin d'étudier l'anatomie de la chambre de chasse du ventricule gauche jusqu'au tronc brachio-céphalique droit. A l'aide de programmes de reconstructions multiplanaires et de segmentation automatique, différents diamètres et longueurs considérés comme importants pour les futurs traitements par transcathéter ont été mesurés. Les valeurs sont exprimées en moyennes, médianes, maximums, minimums, écart-types et en coefficients de variation. Les variations de diamètre de l'aorte ascendante durant le cycle cardiaque ont été aussi considérées. Résultats : Le diamètre moyen de la chambre de chasse du ventricule gauche était de 20.3+/-3.4 mm. Au niveau du sinus coronaire de l'aorte, il était de 34.2+/-4.1 mm et au niveau de la jonction sinotubulaire il était de 29.7+/-3.4 mm. Le diamètre moyen de l'aorte ascendante était de 32.7+/-3.8 mm. Le coefficient de variation de ces mesures variait de 12 à 17%. La distance moyenne entre l'insertion proximale des valvules aortiques et le départ du tronc brachio-céphalique droit était de 92.6+/-11.8 mm. La distance moyenne entre l'insertion proximale des valvules aortiques et l'origine de l'artère coronaire proximale était de 12.1+/-3.7 mm avec un coefficient de variation de 31%. La distance moyenne entre les deux ostia coronaires était de 7.2+/-3.1 mm avec un coefficient de variation de 43%. La longueur moyenne du petit arc de l'aorte ascendante entre l'artère coronaire gauche et le tronc brachio-céphalique droit était de 52.9+/-9.5 mm. La longueur moyenne de la continuité fibreuse entre la valve aortique et la valvule mitrale antérieure était de 14.6+/-3.3 mm avec un coefficient de variation de 23%. L'aire moyenne de la valve aortique était de 582.0+/-131.9 mm2. La variation du diamètre antéro-postérieur et transverse de l'aorte ascendante était respectivement de 8.4% et de 7.3%. Conclusion Il existe d'importantes variations inter-individuelles dans les mesures de l'aorte ascendante avec cependant des variations intra-individuelles faibles durant le cycle cardiaque. De ce fait, une approche personnalisée pour chaque patient est recommandée dans la confection des futures endoprothèses de l'aorte ascendante. Le scanner synchronisé au rythme cardiaque jouera un rôle prépondérant dans le bilan préthérapeutique. Abstract : The aim of this study was to provide an insight into normative values of the ascending aorta in regards to novel endovascular procedures using ECG-gated multi-detector CT angiography. Seventy-seven adult patients without ascending aortic abnormalities were evaluated. Measurements at relevant levels of the aortic root and ascending aorta were obtained. Diameter variations of the ascending aorta during cardiac cycle were also considered. Mean diameters (mm) were as follows: LV outflow tract 20.3+/-3.4, coronary sinus 34.2+/-4.1, sinotubular junction 29.7+-3.4 and mid ascending aorta 32.7+/-3.8 with coefficients of variation (CV) ranging from 12 to 17%. Mean distances (mm) were: from the plane passing through the proximal insertions of the aortic valve cusps to the right brachio-cephalic artery (BCA) 92.6111.8, from the plane passing through the proximal insertions of the aortic valve cusps to the proximal coronary ostium 12.1+/-3.7, and between both coronary ostia 7.2+/-3.1, minimal arc of the ascending aorta from left coronary ostium to right BCA 52.9 X9.5, and the fibrous continuity between the aortic valve and the anterior leaflet of the mitral valve 14.óf3.3, CV 13-43%. Mean aortic valve area was 582+-131.9 mm2. The variations of the antero-posterior and transverse diameters of the ascending aorta during the cardiac cycle were 8.4% and 7.3%, respectively. Results showed large inter-individual variations in diameters and distances but with limited intra-individual variations during the cardiac cycle. A personalized approach for planning endovascular devices must be considered.