Eduard Gratacós

Abstract: Objectives To construct gestational age (GA)-based reference ranges for the uterine artery (UtA) mean pulsatility index (PI) at 11-41 weeks of pregnancy. Methods A prospective cross-sectional observational study was carried out of 20 consecutive singleton pregnancies for each completed gestational week at 11-41 weeks. UtAs were examined by color and pulsed Doppler imaging, and the mean PI, as well as the presence or absence of a bilateral protodiastolic notch, were recorded. Polynomials were fitted by means of least-square regression to estimate the relationship between the mean UtA-PI and GA. Results A total of 620 women were included. A second-degree polynomial (Log(e) mean UtA-PI = 1.39 - 0.012 x GA + GA(2) x 0.0000198, with GA measured in days), after a natural logarithmic transformation, was selected to model our data. There was a significant decrease in the mean UtA-PI between 11 weeks (mean PI, 1.79; 95(th) centile, 2.70) and 34 weeks (mean PI, 0.70; 95(th) centile, 0.99). It then became more stable up until 41 weeks (mean PI, 0.65; 95(th) centile, 0.89). Conclusions The mean UtA-PI shows a progressive decrease until the late stages of pregnancy. Reference ranges for mean UtA-PI may have clinical value in screening for placenta-associated diseases in the early stages of pregnancy, and in evaluating patients with pregnancy-induced hypertension and/or small-for-gestational age fetuses during the third trimester.

Abstract: Small fetuses are defined as those with an ultrasound estimated weight below a threshold, most commonly the 10th centile The first clinically relevant step is the distinction of ‘true’ fetal growth restriction (FGR), associated with signs of abnormal fetoplacental function and poorer perinatal outcome, from constitutional small-for-gestational age, with a near-normal perinatal outcome Nowadays such a distinction should not be based solely on umbilical artery Doppler, since this index detects only early-onset severe forms FGR should be diagnosed in the presence of any of the factors associated with a poorer perinatal outcome, including Doppler cerebroplacental ratio, uterine artery Doppler, a growth centile below the 3rd centile, and, possibly in the near future, maternal angiogenic factors Once the diagnosis is established, differentiating into early- and late-onset FGR is useful mainly for research purposes, because it distinguishes two clear phenotypes with differences in severity, association with preeclampsia, and the natural history of fetal deterioration As a second clinically relevant step, man

Abstract: Background Congenital diaphragmatic hernia (CDH) with liver herniation and a lung area to head circumference ratio (LHR) > 1 is associated with a high rate of neonatal death due to pulmonary hypoplasia. Methods We report the development of a minimally invasive and reversible fetoscopic tracheal occlusion (FETO) with a balloon, carried out in 21 consecutive fetuses with severe CDH. Results Endotracheal placement of the balloon was successfully performed in all 21 cases and the mean duration of the operation was 20 (range, 5–54) min. The median gestation at FETO was 26 (range, 25–33) weeks. There were no maternal complications such as hemorrhage, placental abruption or pulmonary edema. In 11 (52.4%) patients there was postoperative prelabor amniorrhexis, which occurred within 2 weeks in five patients and after 2 weeks in six patients. Ultrasound scans after FETO demonstrated an increase in the echogenicity of the lungs within 48 h and improvement in the LHR from a median 0.7 (range, 0.4–0.9) before FETO to 1.8 (range, 1.1–2.9) within 2 weeks following surgery. The median gestation at delivery was 34 (range, 27–38) weeks and in 17 (77.3%) patients delivery occurred after 32 weeks. Nine babies died in the neonatal period due to complications from pulmonary hypoplasia. Surgical repair of the diaphragmatic hernia was carried out in 12 babies and in all but one the defect was extensive and required the insertion of a patch. Ten of these babies survived, and at the time of writing were aged 6–25 (median, 18) months and were developing normally. Survival was 30% in the first group of 10 fetuses and 63.6% in the second group of 11 fetuses. The total number of cases was too small for definite conclusions to be drawn as to the causes of this apparent improvement in survival. Nevertheless, improved survival coincided with a shift in the timing of FETO from the third to the second trimester, the administration of epidural rather than general anesthesia, reduced incidence of postoperative amniorrhexis and a change in the policy on the timing of removal of the balloon from the intrapartum to the prenatal period. During the same period of study there were 17 cases examined in the participating centers that met the criteria for FETO but which declined prenatal therapy. In all cases there was isolated left-sided CDH with liver in the thorax and LHR of 0.4–0.9 (mean, 0.7). In five cases the parents elected to terminate the pregnancy. In the 12 cases with expectant management all babies were liveborn but 11 died in the neonatal period due to pulmonary hypoplasia and only one (8.3%) survived. Conclusion Severe CDH can be successfully treated with FETO, which is minimally invasive and may improve postnatal survival. Copyright © 2004 ISUOG. Published by John Wiley & Sons, Ltd.

Abstract: Background—Fetal growth restriction (FGR) affects 5% to 10% of newborns and is associated with increased cardiovascular mortality in adulthood. The most commonly accepted hypothesis is that fetal metabolic programming leads secondarily to diseases associated with cardiovascular disease, such as obesity, diabetes mellitus, and hypertension. Our main objective was to evaluate the alternative hypothesis that FGR induces primary cardiac changes that persist into childhood. Methods and Results—Within a cohort of fetuses with growth restriction identified in fetal life and followed up into childhood, we randomly selected 80 subjects with FGR and compared them with 120 normally grown fetuses, matched for gender, birth date, and gestational age at birth. Cardiovascular assessment was performed in childhood (mean age of 5 years). Compared with control subjects, children with FGR had a different cardiac shape, with increased transversal diameters and more globular cardiac ventricles. Although left ejection fraction was similar among the study groups, stroke volume was reduced significantly, which was compensated for by an increased heart rate to maintain output in severe FGR. This was associated with subclinical longitudinal systolic dysfunction (decreased myocardial peak velocities) and diastolic changes (increased E/E ratio and E deceleration time). Children with FGR also had higher blood pressure and increased intima-media thickness. For all parameters evaluated, there was a linear increase with the severity of growth restriction. Conclusions—These findings suggest that FGR induces primary cardiac and vascular changes that could explain the increased predisposition to cardiovascular disease in adult life. If these results are confirmed, the impact of strategies with beneficial effects on cardiac remodeling should be explored in children with FGR. (Circulation. 2010;121:2427-2436.)

Abstract: Objectives To examine operative and perinatal aspects of fetal endoscopic tracheal occlusion (FETO) in congenital diaphragmatic hernia (CDH). Methods This was a multicenter study of singleton pregnancies with CDH treated by FETO. The entry criteria for FETO were severe CDH on the basis of sonographic evidence of intrathoracic herniation of the liver and low lung area to head circumference ratio (LHR) defined as the observed to the expected normal mean for gestation (o/e LHR) equivalent to an LHR of 1o r less. Results FETO was carried out in 210 cases, including 175 cases with left-sided, 34 right-sided and one with bilateral CDH. In 188 cases the CDH was isolated and in 22 there was an associated defect. FETO was performed at a median gestational age of 27.1 (range, 23.0–33.3) weeks. The first eight cases were done under general anesthesia, but subsequently either regional or local anesthesia was used. The median duration of FETO was 10 (range, 3–93) min. Successful placement of the balloon at the first procedure was achieved in 203 (96.7%) cases. Spontaneous preterm prelabor rupture of membranes (PPROM) occurred in 99 (47.1%) cases at 3–83 (median, 30) days after FETO and within 3 weeks of the procedure in 35 (16.7%) cases. Removal of the balloon was prenatal either by fetoscopy or ultrasound-guided puncture, intrapartum by ex-utero intrapartum treatment, or postnatal either by tracheoscopy or percutaneous puncture. Delivery was at 25.7–41.0 (median, 35.3) weeks and before 34 weeks in 65 (30.9%) cases. In 204 (97.1%) cases the babies were live born and 98 (48.0%) were discharged from the hospital alive. There were 10 deaths directly related to difficulties with removal of the balloon. Significant prediction of survival was provided by the o/e LHR and gestational age at delivery. On the basis of the relationship between survival and o/e LHR in expectantly managed fetuses with CDH, as reported in the antenatal CDH registry, we estimated that in fetuses with left CDH treated with FETO the survival rate increased from 24.1% to 49.1%, and in right CDH survival increased from 0% to 35.3% (P < 0.001). Conclusions FETO in severe CDH is associated with a high incidence of PPROM and preterm delivery but a substantial improvement in survival. Copyright  2009 ISUOG. Published by John Wiley & Sons, Ltd.

Abstract: Probability Distributions.- Linear Models for Regression.- Linear Models for Classification.- Neural Networks.- Kernel Methods.- Sparse Kernel Machines.- Graphical Models.- Mixture Models and EM.- Approximate Inference.- Sampling Methods.- Continuous Latent Variables.- Sequential Data.- Combining Models.

Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Abstract: The human brain is a complex system whose topological organization can be represented using connectomics. Recent studies have shown that human connectomes can be constructed using various neuroimaging technologies and further characterized using sophisticated analytic strategies, such as graph theory. These methods reveal the intriguing topological architectures of human brain networks in healthy populations and explore the changes throughout normal development and aging and under various pathological conditions. However, given the huge complexity of this methodology, toolboxes for graph-based network visualization are still lacking. Here, using MATLAB with a graphical user interface (GUI), we developed a graph-theoretical network visualization toolbox, called BrainNet Viewer, to illustrate human connectomes as ball-and-stick models. Within this toolbox, several combinations of defined files with connectome information can be loaded to display different combinations of brain surface, nodes and edges. In addition, display properties, such as the color and size of network elements or the layout of the figure, can be adjusted within a comprehensive but easy-to-use settings panel. Moreover, BrainNet Viewer draws the brain surface, nodes and edges in sequence and displays brain networks in multiple views, as required by the user. The figure can be manipulated with certain interaction functions to display more detailed information. Furthermore, the figures can be exported as commonly used image file formats or demonstration video for further use. BrainNet Viewer helps researchers to visualize brain networks in an easy, flexible and quick manner, and this software is freely available on the NITRC website (www.nitrc.org/projects/bnv/).

Abstract: Experimental Neurology By Prof Paul Glees Pp xii + 532 (Oxford: Clarendon Press; London: Oxford University Press, 1961) 75s net