Now showing items 1-20 of 6739

    • Increased use of cross-sectional imaging for follow-up does not improve post-recurrence survival of surgically treated initially localized R.C.C.: results from a European multicenter database (R.E.C.U.R.).

      Dabestani, Saeed; Beisland, Christian; Stewart, Grant D; Bensalah, Karim; Gudmundsson, Eirikur; Lam, Thomas B; Gietzmann, William; Zakikhani, Paimaun; Marconi, Lorenzo; Fernandéz-Pello, Sergio; Monagas, Serenella; Williams, Samuel P; Powles, Thomas; Van Werkhoven, Erik; Meijer, Richard; Volpe, Alessandro; Staehler, Michael; Ljungberg, Börje; Bex, Axel; 1 a Department of Clinical Sciences Lund , Lund University, Skane University Hospital , Lund , Sweden. 2 b Department of Urology , Haukeland University Hospital , Bergen , Norway. 3 c Department of Clinical Medicine , University of Bergen , Bergen , Norway. 4 d Department of Surgery , Academic Urology Group, University of Cambridge , Cambridge , United Kingdom. 5 e Department of Urology , University of Rennes , Rennes , France. 6 f Department of Urology , Landspitali University Hospital , Reykjavik , Iceland. 7 g Academic Urology Unit , University of Aberdeen , Aberdeen , United Kingdom. 8 h Department of Urology , Aberdeen Royal Infirmary , Aberdeen , United Kingdom. 9 i Department of Urology , Coimbra University Hospital , Coimbra , Portugal. 10 j Department of Urology , Cabueñes University Hospital , Gijón , Spain. 11 k Department of Urology , San Agustin University Hospital , Aviles , Spain. 12 l Medical School , University of Edinburgh , Edinburgh , United Kingdom. 13 m Barts Cancer Institute , Queen Mary University of London , London , United Kingdom. 14 n Department of Bioinformatics and Statistics , The Netherlands Cancer Institute , Amsterdam , The Netherlands. 15 o Department of Urology , University Medical Center Utrecht , Utrecht , The Netherlands. 16 p Department of Urology , University of Eastern Piedmont , Novara , Italy. 17 q Department of Urology , Klinikum Grosshadern, Ludwig Maximilians University of Munich , Munich , Germany. 18 r Department of Surgical and Perioperative Sciences , Umeå University , Umeå , Sweden. 19 s Division of Surgical Oncology, Department of Urology , The Netherlands Cancer Institute , Amsterdam , The Netherlands. (Taylor & Francis, 2019-03-25)
      Modality and frequency of image-based renal cell carcinoma (R.C.C.) follow-up strategies are based on risk of recurrence. Using the R.E.C.U.R.-database, frequency of imaging was studied in regard to prognostic risk groups. Furthermore, it was investigated whether imaging modality utilized in contemporary follow-up were associated with outcome after detection of recurrence. Moreover, outcome was compared based on whether the assessment of potential curability was a pre-defined set of criteria's (per-protocol) or stated by the investigator. Consecutive non-metastatic R.C.C. patients (n = 1,612) treated with curative intent at 12 institutes across eight European countries between 2006 and 2011 were included. Leibovich or U.I.S.S. risk group, recurrence characteristics, imaging modality, frequency and survival were recorded. Primary endpoints were overall survival (O.S.) after detection of recurrence and frequency of features associated with favourable outcome (non-symptomatic recurrences and detection within the follow-up-programme). Recurrence occurred in 336 patients. Within low, intermediate and high risk for recurrence groups, the frequency of follow-up imaging was highest in the early phase of follow-up and decreased significantly over time (p < 0.001). However, neither the image modality for detection nor ≥ 50% cross-sectional imaging during follow-up were associated with improved O.S. after recurrence. Differences between per protocol and investigator based assessment of curability did not translate into differences in O.S. As expected, the frequency of imaging was highest during early follow-up. Cross-sectional imaging use for detection of recurrences following surgery for localized R.C.C. did not improve O.S. post-recurrence. Prospective studies are needed to determine the value of imaging in follow-up.
    • Sequence variation at ANAPC1 accounts for 24% of the variability in corneal endothelial cell density.

      Ivarsdottir, Erna V; Benonisdottir, Stefania; Thorleifsson, Gudmar; Sulem, Patrick; Oddsson, Asmundur; Styrkarsdottir, Unnur; Kristmundsdottir, Snaedis; Arnadottir, Gudny A; Thorgeirsson, Gudmundur; Jonsdottir, Ingileif; Zoega, Gunnar M; Thorsteinsdottir, Unnur; Gudbjartsson, Daniel F; Jonasson, Fridbert; Holm, Hilma; Stefansson, Kari; 1 deCODE genetics/Amgen, Reykjavik, Iceland. 2 School of Engineering and Natural Sciences, University of Iceland, Reykjavik, Iceland. 3 Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 4 Division of Cardiology, Department of Internal Medicine, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland. 5 Department of Immunology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland. 6 Department of Ophthalmology, Landspitali, The National University Hospital of Iceland, Reykjavik, Iceland. 7 deCODE genetics/Amgen, Reykjavik, Iceland. hilma.holm@decode.is. 8 deCODE genetics/Amgen, Reykjavik, Iceland. kari.stefansson@decode.is. 9 Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. kari.stefansson@decode.is. (Nature Publishing Group, 2019-03-20)
      The corneal endothelium is vital for transparency and proper hydration of the cornea. Here, we conduct a genome-wide association study of corneal endothelial cell density (cells/mm2), coefficient of cell size variation (CV), percentage of hexagonal cells (HEX) and central corneal thickness (CCT) in 6,125 Icelanders and find associations at 10 loci, including 7 novel. We assess the effects of these variants on various ocular biomechanics such as corneal hysteresis (CH), as well as eye diseases such as glaucoma and corneal dystrophies. Most notably, an intergenic variant close to ANAPC1 (rs78658973[A], frequency = 28.3%) strongly associates with decreased cell density and accounts for 24% of the population variance in cell density (β = -0.77 SD, P = 1.8 × 10-314) and associates with increased CH (β = 0.19 SD, P = 2.6 × 10-19) without affecting risk of corneal diseases and glaucoma. Our findings indicate that despite correlations between cell density and eye diseases, low cell density does not increase the risk of disease.
    • Mapping of Signaling Pathways Linked to sIgAD Reveals Impaired IL-21 Driven STAT3 B-Cell Activation.

      Lemarquis, Andri L; Theodors, Fannar; Einarsdottir, Helga K; Ludviksson, Bjorn R; 1 Department of Immunology, Landspítali-The National University Hospital of Iceland, Reykjavík, Iceland. 2 Faculty of Medicine, University of Iceland, Reykjavík, Iceland. (Frontiers Research Foundation, 2019-03)
      Objectives: It has recently been shown that individuals with selective IgA deficiency (sIgAD) have defective B cell responses both to T cell dependent and independent mimicking stimulations. The complex intracellular signaling pathways from different stimuli leading to IgA isotype switching have not been fully elucidated. Thus, the main objective of this study was to delineate these pathways and their potential role in the immunopathology linked to sIgAD. Materials and Methods: PBMCs from 10 individuals with sIgAD and 10 healthy controls (HC) were activated in vitro via either a T cell dependent or independent mimicking stimulation. Intracellular phosphorylation of pSTAT3, pSTAT5, pSTAT6, and as pERK1/2 was evaluated in T and B cells using phosphoflow cytometry. Results: By evaluating T cell dependent cytokine driven pathways linked to IgA isotype induction we identified a defect involving an IL-21 driven STAT3 activation isolated to B cells in sIgAD individuals. However, all other signaling pathways studied were found to be normal compared to HC. In T cell dependent cytokine driven stimulations linked to IgA isotype induction the following patterns emerged: (i) IL-10 led to significant STAT3 activation in both T- and B cells; (ii) IL-4 stimulation was predominantly confined to STAT6 activation in both T- and B cells, with some effects on STAT3 activation in T-cells; (iii) as expected, of tested stimuli, IL-2 alone activated STAT5 and some STAT3 activation though in both cases only in T-cells; (iv) IL-21 induced significant activation of STAT3 in both T- and B cells, with some effects on STAT5 activation in T-cells; and finally (v) synergistic effects were noted of IL-4+IL-10 on STAT5 activation in T-cells, and possibly STAT6 in both T- and B cells. On the other hand, CPG induced T cell independent activation was confined to ERK1/2 activation in B cells. Conclusion: Our results indicate a diminished STAT3 phosphorylation following IL-21 stimulation solely in B cells from sIgAD individuals. This can represent aberrant germinal center reactions or developmental halt. Thus, our work provides further insight into the unraveling of the previously hypothesized role of IL-21 to reconstitute immunoglobulin production in primary antibody deficiencies.
    • Integrative cognitive remediation for early psychosis: Results from a randomized controlled trial

      Vidarsdottir, Olina G; Roberts, David L; Twamley, Elizabeth W; Gudmundsdottir, Berglind; Sigurdsson, Engilbert; Magnusdottir, Brynja B; [ 1 ] Natl Univ Hosp Reykjavik, Landspitali, Dept Psychiat, Reykjavik, Iceland Show more [ 2 ] Univ Iceland, Fac Med, Sch Hlth Sci, Vatnsmyrarvegur 16, IS-101 Reykjavik, Iceland Show more [ 3 ] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Div Community Recovery Res & Training, San Antonio, TX 78229 USA Show more [ 4 ] Univ Calif, Dept Psychiat, La Jolla, CA USA Show more [ 5 ] VA San Diego Healthcare Syst, Ctr Excellence Stress & Mental Hlth & Res Serv, San Diego, CA USA Show more [ 6 ] Reykjavik Univ, Dept Psychol, Menntavegur 1, IS-101 Reykjavik, Iceland (ELSEVIER IRELAND, 2019-03)
      Early application of cognitive remediation may help prevent the development of long-term functional impairments that characterize psychotic disorders. Interventions that encompass both neurocognitive and social-cognitive training may work synergistically to bridge the gap between cognitive gains and functional outcomes in early psychosis. We integrated three cognitive remediation approaches: Neuropsychological Educational Approach to Remediation (NEAR), Compensatory Cognitive Training (CCT), and Social Cognition and Interaction Training (SCIT), and evaluated the effects on cognition, clinical symptoms, self-assessed and informant-assessed social functioning in early psychosis. A total of 49 patients diagnosed with primary psychotic disorder seeking service at an early-intervention service in Iceland were randomized to either a waiting-list control group (n = 24) or a 12-week group-based integrative cognitive remediation (n = 25). Neurocognition, social cognition, community functioning and clinical symptoms were assessed at baseline and post-treatment. The intervention group showed significant improvements in verbal memory, cognitive flexibility, working memory, ToM and a significant reduction in hostile attributions, compared to those receiving standard treatment alone, but there were no differences between groups on measures of social functioning or clinical symptoms. The intervention was well tolerated and received high treatment satisfaction ratings. Findings indicate that integrated cognitive remediation has potential to improve neurocognition and social cognition in early psychosis.
    • Integrated analysis of population genomics, transcriptomics and virulence provides novel insights into Streptococcus pyogenes pathogenesis.

      Kachroo, Priyanka; Eraso, Jesus M; Beres, Stephen B; Olsen, Randall J; Zhu, Luchang; Nasser, Waleed; Bernard, Paul E; Cantu, Concepcion C; Saavedra, Matthew Ojeda; Arredondo, María José; Strope, Benjamin; Do, Hackwon; Kumaraswami, Muthiah; Vuopio, Jaana; Gröndahl-Yli-Hannuksela, Kirsi; Kristinsson, Karl G; Gottfredsson, Magnus; Pesonen, Maiju; Pensar, Johan; Davenport, Emily R; Clark, Andrew G; Corander, Jukka; Caugant, Dominique A; Gaini, Shahin; Magnussen, Marita Debess; Kubiak, Samantha L; Nguyen, Hoang A T; Long, S Wesley; Porter, Adeline R; DeLeo, Frank R; Musser, James M; 1 Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, TX, USA. 2 Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA. 3 Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA. 4 Institute of Biomedicine, Medical Microbiology and Immunology, University of Turku, Turku, Finland. 5 National Institute for Health and Welfare, Helsinki, Finland. 6 Department of Clinical Microbiology, Landspitali University Hospital, Reykjavik, Iceland. 7 Faculty of Medicine, School of Health Sciences, University of Iceland, Reykjavik, Iceland. 8 Department of Infectious Diseases, Landspitali University Hospital, Reykjavik, Iceland. 9 Helsinki Institute of Information Technology, Department of Mathematics and Statistics, University of Helsinki, Helsinki, Finland. 10 Department of Computer Science, Aalto University, Espoo, Finland. 11 Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY, USA. 12 Department of Biostatistics, University of Oslo, Oslo, Norway. 13 Division for Infection Control and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway. 14 Medical Department, Infectious Diseases Division, National Hospital of the Faroe Islands, Tórshavn, Denmark. 15 Department of Infectious Diseases, Odense University Hospital, Odense, Denmark. 16 Department of Clinical Research, University of Southern Denmark, Odense, Denmark. 17 Department of Science and Technology, Centre of Health Research, University of the Faroe Islands, Tórshavn, Denmark. 18 Thetis, Food and Environmental Laboratory, Torshavn, Denmark. 19 Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA. 20 Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, TX, USA. JMMusser@houstonmethodist.org. 21 Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA. JMMusser@houstonmethodist.org. 22 Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA. JMMusser@houstonmethodist.org. (Nature Publishing Group, 2019-03)
      Streptococcus pyogenes causes 700 million human infections annually worldwide, yet, despite a century of intensive effort, there is no licensed vaccine against this bacterium. Although a number of large-scale genomic studies of bacterial pathogens have been published, the relationships among the genome, transcriptome, and virulence in large bacterial populations remain poorly understood. We sequenced the genomes of 2,101 emm28 S. pyogenes invasive strains, from which we selected 492 phylogenetically diverse strains for transcriptome analysis and 50 strains for virulence assessment. Data integration provided a novel understanding of the virulence mechanisms of this model organism. Genome-wide association study, expression quantitative trait loci analysis, machine learning, and isogenic mutant strains identified and confirmed a one-nucleotide indel in an intergenic region that significantly alters global transcript profiles and ultimately virulence. The integrative strategy that we used is generally applicable to any microbe and may lead to new therapeutics for many human pathogens.
    • Home sleep apnea testing: comparison of manual and automated scoring across international sleep centers.

      Magalang, Ulysses J; Johns, Jennica N; Wood, Katherine A; Mindel, Jesse W; Lim, Diane C; Bittencourt, Lia R; Chen, Ning-Hung; Cistulli, Peter A; Gíslason, Thorarinn; Arnardottir, Erna S; Penzel, Thomas; Tufik, Sergio; Pack, Allan I; 1 Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, 201 Davis Heart and Lung Research Institute, 473 West 12th Avenue, Columbus, OH, 43210, USA. ulysses.magalang@osumc.edu. 2 Neuroscience Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, USA. ulysses.magalang@osumc.edu. 3 Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, The Ohio State University Wexner Medical Center, 201 Davis Heart and Lung Research Institute, 473 West 12th Avenue, Columbus, OH, 43210, USA. 4 Center for Sleep and Circadian Neurobiology, Division of Sleep Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. 5 Departamento de Psicobiologia, Universidade Federal de São Paulo, São Paulo, Brazil. 6 Division of Pulmonary, Critical Care, and Sleep Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan. 7 Charles Perkins Centre, University of Sydney, Camperdown, Australia. 8 Department of Respiratory and Sleep Medicine, Royal North Shore Hospital, Sydney, Australia. 9 Department of Sleep Medicine, Landspitali University Hospital, Reykjavik, Iceland. 10 Medical Faculty, University of Iceland, Reykjavik, Iceland. 11 Interdisciplinary Center of Sleep Medicine, Charité University Hospital, Berlin, Germany. (Springer Heidelberg, 2019-03)
      To determine the agreement between the manual scoring of home sleep apnea tests (HSATs) by international sleep technologists and automated scoring systems. Fifteen HSATs, previously recorded using a type 3 monitor, were saved in European Data Format. The studies were scored by nine experienced technologists from the sleep centers of the Sleep Apnea Global Interdisciplinary Consortium (SAGIC) using the locally available software. Each study was scored separately by human scorers using the nasal pressure (NP), flow derived from the NP signal (transformed NP), or respiratory inductive plethysmography (RIP) flow. The same procedure was followed using two automated scoring systems: Remlogic (RLG) and Noxturnal (NOX). The intra-class correlation coefficients (ICCs) of the apnea-hypopnea index (AHI) scoring using the NP, transformed NP, and RIP flow were 0.96 [95% CI 0.93-0.99], 0.98 [0.96-0.99], and 0.97 [0.95-0.99], respectively. Using the NP signal, the mean differences in AHI between the average of the manual scoring and the automated systems were - 0.9 ± 3.1/h (AHI There is very strong agreement in the scoring of the AHI for HSATs between the automated systems and experienced international technologists. Automated scoring of HSATs using commercially available software may be useful to standardize scoring in future endeavors involving international sleep centers.
    • Interrogating the Genetic Determinants of Tourette's Syndrome and Other Tic Disorders Through Genome-Wide Association Studies.

      Yu, Dongmei; Sul, Jae Hoon; Tsetsos, Fotis; Nawaz, Muhammad S; Huang, Alden Y; Zelaya, Ivette; Illmann, Cornelia; Osiecki, Lisa; Darrow, Sabrina M; Hirschtritt, Matthew E; Greenberg, Erica; Muller-Vahl, Kirsten R; Stuhrmann, Manfred; Dion, Yves; Rouleau, Guy; Aschauer, Harald; Stamenkovic, Mara; Schlögelhofer, Monika; Sandor, Paul; Barr, Cathy L; Grados, Marco; Singer, Harvey S; Nöthen, Markus M; Hebebrand, Johannes; Hinney, Anke; King, Robert A; Fernandez, Thomas V; Barta, Csaba; Tarnok, Zsanett; Nagy, Peter; Depienne, Christel; Worbe, Yulia; Hartmann, Andreas; Budman, Cathy L; Rizzo, Renata; Lyon, Gholson J; McMahon, William M; Batterson, James R; Cath, Danielle C; Malaty, Irene A; Okun, Michael S; Berlin, Cheston; Woods, Douglas W; Lee, Paul C; Jankovic, Joseph; Robertson, Mary M; Gilbert, Donald L; Brown, Lawrence W; Coffey, Barbara J; Dietrich, Andrea; Hoekstra, Pieter J; Kuperman, Samuel; Zinner, Samuel H; Luðvigsson, Pétur; Sæmundsen, Evald; Thorarensen, Ólafur; Atzmon, Gil; Barzilai, Nir; Wagner, Michael; Moessner, Rainald; Ophoff, Roel; Pato, Carlos N; Pato, Michele T; Knowles, James A; Roffman, Joshua L; Smoller, Jordan W; Buckner, Randy L; Willsey, A Jeremy; Tischfield, Jay A; Heiman, Gary A; Stefansson, Hreinn; Stefansson, Kári; Posthuma, Danielle; Cox, Nancy J; Pauls, David L; Freimer, Nelson B; Neale, Benjamin M; Davis, Lea K; Paschou, Peristera; Coppola, Giovanni; Mathews, Carol A; Scharf, Jeremiah M; [ 1 ] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Genom Med, Dept Psychiat, Boston, MA 02114 USA [ 2 ] Brd Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02142 USA Show more [ 3 ] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, David Geffen Sch Med, Los Angeles, CA 90024 USA Show more [ 4 ] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA Show more [ 5 ] Democritus Univ Thrace, Dept Mol Biol & Genet, Xanthi, Greece Show more [ 6 ] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA [ 7 ] DeCODE Genet Amgen, Reykjavik, Iceland Show more [ 8 ] Univ Calif Los Angeles, Bioinformat Interdept Program, Los Angeles, CA USA Show more [ 9 ] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA Show more [ 10 ] Univ Calif San Francisco, Dept Psychiat, UCSF Weill Inst Neurosci, San Francisco, CA 94143 USA Show more [ 11 ] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA Show more [ 12 ] Hannover Med Sch, Clin Psychiat Social Psychiat & Psychotherapy, Hannover, Germany Show more [ 13 ] Hannover Med Sch, Inst Human Genet, Hannover, Germany Show more [ 14 ] Univ Montreal, McGill Univ Hlth Ctr, Montreal, PQ, Canada Show more [ 15 ] McGill Univ, Dept Neurol & Neurosurg, Montreal Neurol Inst, Montreal, PQ, Canada Show more [ 16 ] Med Univ Vienna, Dept Psychiat & Psychotherapy, Vienna, Austria [ 17 ] Biopsychosocial Corp, Vienna, Austria Show more [ 18 ] Univ Hlth Network, Youthdale Treatment Centres, Toronto, ON, Canada Show more [ 19 ] Univ Toronto, Toronto, ON, Canada Show more [ 20 ] Univ Hlth Network, Hosp Sick Children, Krembil Res Inst, Toronto, ON, Canada Show more [ 21 ] Johns Hopkins Univ, Sch Med, Baltimore, MD USA Show more [ 22 ] Univ Bonn, Med Sch, Inst Human Genet, Univ Hosp Bonn, Bonn, Germany Show more [ 23 ] Univ Duisburg Essen, Dept Child & Adolescent Psychiat Psychosomat & Ps, Univ Hosp Essen, Essen, Germany Show more [ 24 ] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA Show more [ 25 ] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA Show more [ 26 ] Semmelweis Univ, Inst Med Chem Mol Biol & Pathobiochem, Budapest, Hungary [ 27 ] Vadaskert Child & Adolescent Psychiat Hosp, Budapest, Hungary Show more [ 28 ] Univ Duisburg Essen, Inst Human Genet, Univ Hosp Essen, Essen, Germany Show more [ 29 ] UPMC Univ Paris 06, Sorbonne Univ, CNRS UMR 7225, UMR S 1127,ICM, Paris, France Show more [ 30 ] Grp Hosp Pitie Salpetriere, French Reference Ctr Gilles Tourette Syndrome, Paris, France Show more [ 31 ] Grp Hosp Pitie Salpetriere, AP HP, Dept Neurol, Paris, France [ 32 ] Zucker Sch Med Hofstra Northwell, Hempstead, NY USA Show more [ 33 ] Univ Catania, Dept Clin & Expt Med, Child Neuropsychiat, Catania, Italy Show more [ 34 ] Cold Spring Harbor Lab, Stanley Inst Cognit Genom, POB 100, Cold Spring Harbor, NY 11724 USA Show more [ 35 ] Univ Utah, Dept Psychiat, Salt Lake City, UT USA Show more [ 36 ] Childrens Mercy Hosp, Kansas City, MO 64108 USA Show more [ 37 ] Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands Show more [ 38 ] Univ Groningen, Groningen, Netherlands [ 39 ] Drenthe Mental Hlth Ctr, Groningen, Netherlands Show more [ 40 ] Univ Florida, Dept Neurol, Fixel Ctr Neurol Dis, McKnight Brain Inst, Gainesville, FL USA Show more [ 41 ] Penn State Univ, Coll Med, Hershey, PA USA Show more [ 42 ] Marquette Univ, Milwaukee, WI 53233 USA Show more [ 43 ] Univ Wisconsin, Milwaukee, WI 53201 USA Show more [ 44 ] Tripler Army Med Ctr, Honolulu, HI 96859 USA Show more [ 45 ] Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA Show more [ 46 ] Baylor Coll Med, Dept Neurol, Parkinsons Dis Ctr, Houston, TX 77030 USA Show more [ 47 ] Baylor Coll Med, Dept Neurol, Movement Disorders Clin, Houston, TX 77030 USA Show more [ 48 ] UCL, Div Psychiat, Dept Neuropsychiat, London, England Show more [ 49 ] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA Show more [ 50 ] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA Show more [ 51 ] Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA Show more [ 52 ] Univ Groningen, Univ Med Ctr Groningen, Dept Child & Adolescent Psychiat, Groningen, Netherlands Show more [ 53 ] Univ Iowa, Carver Coll Med, Iowa City, IA USA Show more [ 54 ] Univ Washington, Dept Pediat, Seattle, WA 98195 USA Show more [ 55 ] Landspitalinn Univ Hosp, Dept Pediat, Reykjavik, Iceland Show more [ 56 ] Univ Iceland, Fac Med, Reykjavik, Iceland [ 57 ] State Diagnost & Counselling Ctr, Kopavogur, Iceland Show more [ 58 ] Albert Einstein Coll Med, Dept Genet, Bronx, NY 10467 USA Show more [ 59 ] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA Show more [ 60 ] Univ Haifa, Dept Human Biol, Haifa, Israel Show more [ 61 ] Univ Bonn, Dept Psychiat & Psychotherapy, Bonn, Germany Show more [ 62 ] Univ Tubingen, Dept Psychiat & Psychotherapy, Tubingen, Germany Show more [ 63 ] SUNY Downstate Med Ctr, Brooklyn, NY 11203 USA Show more [ 64 ] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Res, Dept Radiol, Charlestown, MA USA Show more [ 65 ] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA Show more [ 66 ] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA Show more [ 67 ] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA Show more [ 68 ] Univ Calif San Francisco, UCSF Weill Inst Neurosci, Inst Neurodegenerat Dis, San Francisco, CA 94143 USA Show more [ 69 ] Rutgers State Univ, Dept Genet, Piscataway, NJ USA Show more [ 70 ] Rutgers State Univ, Human Genet Inst New Jersey, Piscataway, NJ USA Show more [ 71 ] Vrije Univ Amsterdam, Dept Complex Trait Genet, Ctr NeuroGenom & Cognit Res, Amsterdam, Netherlands Show more [ 72 ] Vanderbilt Univ, Med Ctr, Div Genet Med, Vanderbilt Genet Inst, 221 Kirkland Hall, Nashville, TN 37235 USA Show more [ 73 ] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Dept Med, Boston, MA 02114 USA Show more [ 74 ] Univ Florida, Dept Psychiat, Genet Inst, Gainesville, FL 32611 USA Show more [ 75 ] Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA Show more [ 76 ] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA (American Psychiatric Association, 2019-03)
      Tourette's syndrome is polygenic and highly heritable. Genome-wide association study (GWAS) approaches are useful for interrogating the genetic architecture and determinants of Tourette's syndrome and other tic disorders. The authors conducted a GWAS meta-analysis and probed aggregated Tourette's syndrome polygenic risk to test whether Tourette's and related tic disorders have an underlying shared genetic etiology and whether Tourette's polygenic risk scores correlate with worst-ever tic severity and may represent a potential predictor of disease severity. GWAS meta-analysis, gene-based association, and genetic enrichment analyses were conducted in 4,819 Tourette's syndrome case subjects and 9,488 control subjects. Replication of top loci was conducted in an independent population-based sample (706 case subjects, 6,068 control subjects). Relationships between Tourette's polygenic risk scores (PRSs), other tic disorders, ascertainment, and tic severity were examined. GWAS and gene-based analyses identified one genome-wide significant locus within FLT3 on chromosome 13, rs2504235, although this association was not replicated in the population-based sample. Genetic variants spanning evolutionarily conserved regions significantly explained 92.4% of Tourette's syndrome heritability. Tourette's-associated genes were significantly preferentially expressed in dorsolateral prefrontal cortex. Tourette's PRS significantly predicted both Tourette's syndrome and tic spectrum disorders status in the population-based sample. Tourette's PRS also significantly correlated with worst-ever tic severity and was higher in case subjects with a family history of tics than in simplex case subjects. Modulation of gene expression through noncoding variants, particularly within cortico-striatal circuits, is implicated as a fundamental mechanism in Tourette's syndrome pathogenesis. At a genetic level, tic disorders represent a continuous spectrum of disease, supporting the unification of Tourette's syndrome and other tic disorders in future diagnostic schemata. Tourette's PRSs derived from sufficiently large samples may be useful in the future for predicting conversion of transient tics to chronic tic disorders, as well as tic persistence and lifetime tic severity.
    • How Do Family Strengths-Oriented Therapeutic Conversations (FAM-SOTC) Advance Psychiatric Nursing Practice?

      Svavarsdottir, Erla Kolbrun; Gisladottir, Margret; 1 Professor and Academic Chair of Family Nursing, Faculty of Nursing, School of Health Sciences, University of Iceland, and Academic Chair of Family Nursing, Landspitali-The National University Hospital in Iceland, Reykjavík, Iceland. 2 Psychiatric Clinical Nurse Specialist, Landspitali University Hospital, Landspitali-The National University Hospital in Iceland, Child and Adolescent Psychiatric Division, Reykjavik, Iceland. (Wiley, 2019-03)
      Family nursing interventions, focusing on therapeutic conversations, have been found to benefit primary caregivers dealing with chronic and acute illnesses. Less is known, however, about the benefit of these interventions for partner caregivers. The aims of this study were to develop and test the Family Strengths-Oriented Therapeutic Conversation (FAM-SOTC) intervention for partner caregivers of young individuals with eating disorders (EDs). Eighteen partner caregivers of adolescents and young adults with ED participated in this quasi-experimental study. The FAM-SOTC intervention was offered over 4 months, during which time the focus was on establishing the therapeutic relationship and identification of the family relationships. The five key elements of the FAM-SOTC intervention are (a) drawing forward illness stories; (b) asking therapeutic questions; (c) identifying strength, resiliency, and resources; (d) offering evidence-based information and recommendations; and (e) strengthening helpful beliefs and challenging hindering beliefs. These elements provided the foundation for the study. Significantly higher family support and illness beliefs were reported after five sessions of the FAM-SOTC intervention and again after 3 follow-up booster sessions. The FAM-SOTC intervention demonstrated a positive benefit for participants. The FAM-SOTC intervention was found to benefit families, both in the short and long term, in psychiatry settings. After having participated in five sessions of the FAM-SOTC intervention and 3 booster sessions, partner caregivers of young individuals with ED experienced higher family support and reported better knowledge, more confidence, and more positive illness beliefs regarding the disorder.
    • Elevation in Cell Cycle and Protein Metabolism Gene Transcription in Inactive Colonic Tissue From Icelandic Patients With Ulcerative Colitis.

      Vinayaga-Pavan, Mathena; Frampton, Matthew; Pontikos, Nikolas; Levine, Adam P; Smith, Phillip J; Jonasson, Jon G; Björnsson, Einar S; Segal, Anthony W; Smith, Andrew M; 1 Microbial Diseases, Eastman Dental Institute. 2 Molecular Medicine, Division of Medicine. 3 UCL Genetics Institute, University College London, London, United Kingdom. 4 Department of Pathology, Landspitali University Hospital Reykjavik, Iceland. 5 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 6 Department of Gastroenterology and Hepatology, Landspitali University Hospital, Reykjavik, Iceland. (Oxford University Press, 2019-01-10)
      A combination of genetic and environmental factors is thought to be involved in the pathogenesis of ulcerative colitis (UC). In Iceland, the incidence of UC is one of the highest in the world. The aim of this study was to characterize patients with UC and identify potential germline mutations and pathways that could be associated with UC in this population. Exome sequencing and genome-wide microarray analysis on macroscopically noninflamed colonic mucosa from patients and controls were performed. Exome sequence data were examined for very rare or novel mutations that were over-represented in the UC cohort. Combined matching of variant analysis and downstream influence on transcriptomic expression in the rectum were analyzed. One thousand eight hundred thirty-eight genes were differentially expressed in rectal tissue from UC patients and identified an upregulation in genes associated with cell cycle control and protein processing in the endoplasmic reticulum (ER). Two missense mutations in thiopurine S-methyltransferase (TPMT) with a minor allele frequency of 0.22 in the UC patients compared with a reported 0.062 in the Icelandic population were identified. A predicted damaging mutation in the gene SLC26A3 is potentially associated with increased expression of DUOX2 and DUOXA2 in rectal tissue. Colonic mucosa of UC patients demonstrates evidence of an elevation in genes involving cell proliferation and processing of proteins within the ER. Exome sequencing identified a possible increased prevalence of 2 damaging TPMT variants within the UC population, suggesting screening the UC population before initiation of thiopurine analogue therapy to avoid toxicity associated with these mutations.
    • European postgraduate curriculum in geriatric medicine developed using an international modified Delphi technique.

      Roller-Wirnsberger, Regina; Masud, Tahir; Vassallo, Michael; Zöbl, Martina; Reiter, Raphael; Van Den Noortgate, Nele; Petermans, Jean; Petrov, Ignat; Topinkova, Eva; Andersen-Ranberg, Karen; Saks, Kai; Nuotio, Maria; Bonin-Guillaume, Sylvie; Lüttje, Dieter; Mestheneos, Elizabeth; Szekacs, Bela; Jonsdottir, Anna Björg; O'Neill, Desmond; Cherubini, Antonio; Macijauskiene, Jurate; Leners, Jean-Claude; Fiorini, Anthony; van Iersel, Marianne; Ranhoff, Anette Hylen; Kostka, Tomasz; Duque, Sofia; Prada, Gabriel Ioan; Davidovic, Mladen; Krajcik, Stefan; Kolsek, Marko; Del Nozal, Jesus Mateos; Ekdahl, Anne W; Münzer, Thomas; Savas, Sumru; Knight, Paul; Gordon, Adam; Singler, Katrin; 1 Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, Graz, Austria. 2 Department of Healthcare for Older People, Nottingham University Hospitals NHS Trust, Derby Road, Nottingham, UK. 3 Royal Bournemouth and Christchurch NHS Hospitals Foundation Trust, Castle Lane East, Bournemouth, UK. 4 Department of Geriatric Medicine, Paracelsus Medical University Strubergasse 22, Salzburg, Austria. 5 Department of Geriatric Medicine, Ghent University Hospital Corneel Heymanslaan 10, Gent, Belgium. 6 Geriatric Department, CHU Rue de Gaillarmont 600, Liège, Belgium. 7 Clinical Centre of Endocrinology and Gerontology, Medical University of SofiaBoulevard "Akademik Ivan Evstratiev Geshov" 15, Sofia Center, Sofia, Bulgaria. 8 Department of Gerontology and Geriatrics, 1st Faculty of Medicine, Charles University and General Faculty HospitalOvocný trh 3-5, Staré Mesto, Czechia. 9 Department of Geriatric Medicine, Odense University Hospital and Department of Clinical Research, University of Southern Denmark, J. B. Winsløws Vej 4, Odense, Denmark. 10 Department of Internal Medicine, University of Tartu, Ülikooli 18, Tartu, Estonia. 11 Department of Geriatric Medicine, Seinäjoki Central Hospital, Hanneksenrinne 7, Seinäjoki, Finland. 12 Department of Geriatrics, University of Turku, Turku, Finland. 13 Department of Geriatric Medicine, Hopital de la Timone, 264 Rue Saint Pierre, Marseille 05, Provence-Alpes-Côte d'Azur, France. 14 Medizinische Klinik IV, Geriatrie und Palliativmedizin, Klinikum Osnabrück, Germany. 15 Hellenic Association of Gerontology and Geriatrics, Past President Age Platform Europe, Greece. 16 Hungarian Association of Gerontology and Geriatrics (HAGG). 17 Department of Geriatric Medicine, The National University Hospital of Iceland Landakoti, 101, Reykjavík Iceland. 18 Department of Clinical Gerontology, College Green, Dublin 2, Ireland. 19 Geriatria, Accettazione geriatrica e Centro di ricerca per l'invecchiamento, IRCCS INRCA, Ancona, Italia. 20 Department of Geriatrics, The Faculty of Nursing, Medical Academy Lithuanian, University of Health Sciences, A. Mickeviciaus g. 9, Kaunas, Lithuania. 21 House Omega & LTCF Alzheimer, University of Luxembourg, 2, avenue de l'Université, Esch-sur-Alzette, Luxembourg. 22 The Geriatric Medicine Society of Malta, Karin Grech Hospital, Telghat Gwardamangia, Pieta' Malta PTA, Malta. 23 Department of Geriatric Medicine, Radboud University Medical Centre, Geert Grooteplein Zuid 10, GA Nijmegen, Netherlands. 24 Department of Clinical Science, University of Bergen, Bergen, Norway. 25 Department of Geriatrics, Medical University of Lodz, plac Hallera 1, Lódz, Poland. 26 Internal Medicine Specialist with Geriatrics Competence, Orthogeriatric Unit Coordinator, Internal Medicine Department, Hospital São Francisco Xavier, Centro Hospitalar de Lisboa, Ocidental, Invited Lecturer of Geriatrics, Faculdade de Medicina, Universidade de Lisboa, Estr. Forte do Alto Duque, Lisboa, Portugal. 27 Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, Ana Aslan National Institute of Gerontology and Geriatrics, Romania. 28 Serbian Association of Geriatricians and Gerontologist, Udruženje gerijatara i gerontologa Srbije, Preševska 31, Beograd, Serbia. 29 Geriatric Department, Slovak Medical University, Bratislava, Slovakia. 30 Department of Family Medicine, Faculty of Medicine, University of Ljubljana Korytkova ulica 2, Ljubljana, Slovenia. 31 Servicio de Geriatría. Hospital Universitario Ramón y Cajal, Madrid, Spain. 32 Department of Clinical Sciences Helsingborg, Helsingborg Hospital, Lund University, Svartbrödragränden 3-5, Helsingborg, Sweden. 33 Department of Neurobiology, Care Sciences and Society (NVS), Division of Clinical geriatrics, Solnavägen 1, Solna, Sweden. 34 Department of Geriatrics, Geriatrische Klinik St. Gallen and University of Zürich, Zürich, Switzerland. 35 Section of Geriatrics, Department of Internal Medicine, School of Medicine, Ege University Erzene Mahallesi, Bornova/Izmir, Turkey. 36 Department Geriatric Medicine, Royal Infirmary, Glasgow, UK. 37 CLAHRC-East Midlands 'Caring for Older People and Stroke Survivors' (COPSS), Nottingham Biomedical Research Centre (BRC). 38 Institute of Biomedicine of Ageing, Friedrich Alexander University Erlangen, Schloßplatz 4, Erlangen, Germany. 39 Department of Geriatrics, Klinikum Nürnberg, Paracelsus Private Medical University, Prof.-Ernst-Nathan-Straße 1, Nürnberg, Germany. (Oxford University Press, 2019-02)
      the European Union of Medical Specialists (UEMS-GMS) recommendations for training in Geriatric Medicine were published in 1993. The practice of Geriatric Medicine has developed considerably since then and it has therefore become necessary to update these recommendations. under the auspices of the UEMS-GMS, the European Geriatric Medicine Society (EuGMS) and the European Academy of Medicine of Ageing (EAMA), a group of experts, representing all member states of the respective bodies developed a new framework for education and training of specialists in Geriatric Medicine using a modified Delphi technique. Thirty-two expert panel members from 30 different countries participated in the process comprising three Delphi rounds for consensus. The process was led by five facilitators. the final recommendations include four different domains: 'General Considerations' on the structure and aim of the syllabus as well as quality indicators for training (6 sub-items), 'Knowledge in patient care' (36 sub-items), 'Additional Skills and Attitude required for a Geriatrician' (9 sub-items) and a domain on 'Assessment of postgraduate education: which items are important for the transnational comparison process' (1 item). the current publication describes the development of the new recommendations endorsed by UEMS-GMS, EuGMS and EAMA as minimum training requirements to become a geriatrician at specialist level in EU member states.
    • Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting.

      Chauhan, Ganesh; Adams, Hieab H H; Satizabal, Claudia L; Bis, Joshua C; Teumer, Alexander; Sargurupremraj, Muralidharan; Hofer, Edith; Trompet, Stella; Hilal, Saima; Smith, Albert Vernon; Jian, Xueqiu; Malik, Rainer; Traylor, Matthew; Pulit, Sara L; Amouyel, Philippe; Mazoyer, Bernard; Zhu, Yi-Cheng; Kaffashian, Sara; Schilling, Sabrina; Beecham, Gary W; Montine, Thomas J; Schellenberg, Gerard D; Kjartansson, Olafur; Guðnason, Vilmundur; Knopman, David S; Griswold, Michael E; Windham, B Gwen; Gottesman, Rebecca F; Mosley, Thomas H; Schmidt, Reinhold; Saba, Yasaman; Schmidt, Helena; Takeuchi, Fumihiko; Yamaguchi, Shuhei; Nabika, Toru; Kato, Norihiro; Rajan, Kumar B; Aggarwal, Neelum T; De Jager, Philip L; Evans, Denis A; Psaty, Bruce M; Rotter, Jerome I; Rice, Kenneth; Lopez, Oscar L; Liao, Jiemin; Chen, Christopher; Cheng, Ching-Yu; Wong, Tien Y; Ikram, Mohammad K; van der Lee, Sven J; Amin, Najaf; Chouraki, Vincent; DeStefano, Anita L; Aparicio, Hugo J; Romero, Jose R; Maillard, Pauline; DeCarli, Charles; Wardlaw, Joanna M; Hernández, Maria Del C Valdés; Luciano, Michelle; Liewald, David; Deary, Ian J; Starr, John M; Bastin, Mark E; Muñoz Maniega, Susana; Slagboom, P Eline; Beekman, Marian; Deelen, Joris; Uh, Hae-Won; Lemmens, Robin; Brodaty, Henry; Wright, Margaret J; Ames, David; Boncoraglio, Giorgio B; Hopewell, Jemma C; Beecham, Ashley H; Blanton, Susan H; Wright, Clinton B; Sacco, Ralph L; Wen, Wei; Thalamuthu, Anbupalam; Armstrong, Nicola J; Chong, Elizabeth; Schofield, Peter R; Kwok, John B; van der Grond, Jeroen; Stott, David J; Ford, Ian; Jukema, J Wouter; Vernooij, Meike W; Hofman, Albert; Uitterlinden, André G; van der Lugt, Aad; Wittfeld, Katharina; Grabe, Hans J; Hosten, Norbert; von Sarnowski, Bettina; Völker, Uwe; Levi, Christopher; Jimenez-Conde, Jordi; Sharma, Pankaj; Sudlow, Cathie L M; Rosand, Jonathan; Woo, Daniel; Cole, John W; Meschia, James F; Slowik, Agnieszka; Thijs, Vincent; Lindgren, Arne; Melander, Olle; Grewal, Raji P; Rundek, Tatjana; Rexrode, Kathy; Rothwell, Peter M; Arnett, Donna K; Jern, Christina; Johnson, Julie A; Benavente, Oscar R; Wasssertheil-Smoller, Sylvia; Lee, Jin-Moo; Wong, Quenna; Mitchell, Braxton D; Rich, Stephen S; McArdle, Patrick F; Geerlings, Mirjam I; van der Graaf, Yolanda; de Bakker, Paul I W; Asselbergs, Folkert W; Srikanth, Velandai; Thomson, Russell; McWhirter, Rebekah; Moran, Chris; Callisaya, Michele; Phan, Thanh; Rutten-Jacobs, Loes C A; Bevan, Steve; Tzourio, Christophe; Mather, Karen A; Sachdev, Perminder S; van Duijn, Cornelia M; Worrall, Bradford B; Dichgans, Martin; Kittner, Steven J; Markus, Hugh S; Ikram, Mohammad A; Fornage, Myriam; Launer, Lenore J; Seshadri, Sudha; Longstreth, W T; Debette, Stéphanie; 1 ] Bordeaux Populat Hlth Res Ctr, Bordeaux, France Show more [ 2 ] CEA, CNRS, INSERM, U1219,Grp Imagerie Neurofonct,U5293, Bordeaux, France Show more [ 3 ] Univ Bordeaux, Bordeaux, France Show more [ 4 ] Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France Show more [ 5 ] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands Show more [ 6 ] Erasmus MC, Dept Radiol & Nucl Med, Rotterdam, Netherlands Show more [ 7 ] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands Show more [ 8 ] Erasmus MC, Dept Neurol, Rotterdam, Netherlands Show more [ 9 ] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA Show more [ 10 ] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA Show more [ 11 ] NHLBI, Framingham Heart Study, Bldg 10, Bethesda, MD 20892 USA Show more [ 12 ] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA Show more [ 13 ] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA Show more [ 14 ] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA Show more [ 15 ] Univ Washington, Dept Biostat, Seattle, WA 98195 USA Show more [ 16 ] Univ Washington, Dept Neurol, Seattle, WA 98195 USA Show more [ 17 ] Univ Washington, Dept Pathol, Seattle, WA 98195 USA Show more [ 18 ] Stanford Univ, Pathol, Stanford, CA 94305 USA Show more [ 19 ] Univ Med Greifswald, Inst Community Med, Greifswald, Germany Show more [ 20 ] Univ Med Greifswald, Dept Psychiat & Psychotherapy, Greifswald, Germany Show more [ 21 ] Univ Med Greifswald, Inst Diagnost Radiol & Neuroradiol, Greifswald, Germany Show more [ 22 ] Univ Med Greifswald, Dept Neurol, Greifswald, Germany Show more [ 23 ] Med Univ Graz, Clin Div Neurogeriatr, Dept Neurol, Graz, Austria Show more [ 24 ] Med Univ Graz, Inst Med Informat Stat & Documentat, Graz, Austria Show more [ 25 ] Med Univ Graz, Gottfried Schatz Res Ctr Cell Signaling Metab & A, Inst Mol Biol & Biochem, Graz, Austria Show more [ 26 ] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands Show more [ 27 ] Leiden Univ, Med Ctr, Sect Gerontol & Geriatr, Dept Internal Med, Leiden, Netherlands Show more [ 28 ] Leiden Univ, Med Ctr, Mol Epidemiol, Leiden, Netherlands Show more [ 29 ] Leiden Univ, Med Ctr, Med Stat & Bioinformat, Leiden, Netherlands Show more [ 30 ] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands Show more [ 31 ] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Singapore, Singapore Show more [ 32 ] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore, Singapore Show more [ 33 ] Icelandic Heart Assoc, Kopavogur, Iceland Show more [ 34 ] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA Show more [ 35 ] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA Show more [ 36 ] Ludwig Maximilians Univ Munchen, Klinikum Univ Munchen, Inst Stroke & Dementia Res, Munich, Germany Show more [ 37 ] Univ Cambridge, Clin Neurosci, Cambridge, England Show more [ 38 ] Univ Lincoln, Sch Life Sci, Lincoln, England Show more [ 39 ] German Ctr Neurodegenerat Dis DZNE, Populat Hlth Sci, Bonn, Germany Show more [ 40 ] Univ Med Ctr Utrecht, Dept Med Genet, Utrecht, Netherlands Show more [ 41 ] Univ Med Ctr Utrecht, Dept Neurol, Brain Ctr Rudolf Magnus, Utrecht, Netherlands Show more [ 42 ] Univ Med Ctr Utrecht, Dept Epidemiol, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands Show more [ 43 ] Univ Med Ctr Utrecht, Dept Genet, Ctr Mol Med, Utrecht, Netherlands Show more [ 44 ] Univ Med Ctr Utrecht, Dept Cardiol, Div Heart & Lungs, Utrecht, Netherlands Show more [ 45 ] Univ Utrecht, Utrecht, Netherlands Show more [ 46 ] Lille Univ, INSERM, Lille Univ Hosp, Inst Pasteur Lille, Lille, France Show more [ 47 ] Peking Union Med Coll Hosp, Dept Neurol, Beijing, Peoples R China Show more [ 48 ] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Coral Gables, FL 33124 USA Show more [ 49 ] Univ Miami, Miller Sch Med, Dept Neurol, Coral Gables, FL 33124 USA Show more [ 50 ] Univ Miami, Miller Sch Med, Evelyn F McKnight Brain Inst, Coral Gables, FL 33124 USA Show more [ 51 ] Univ Miami, Miller Sch Med, Dept Epidemiol & Publ Hlth Sci, Coral Gables, FL 33124 USA Show more [ 52 ] Univ Miami, Miller Sch Med, Dr John T Macdonald Fdn, Dept Human Genet, Coral Gables, FL 33124 USA Show more [ 53 ] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA Show more [ 54 ] Landspitali Natl Univ Hosp, Dept Neurol, Reykjavik, Iceland Show more [ 55 ] Landspitali Natl Univ Hosp, Dept Radiol, Reykjavik, Iceland Show more [ 56 ] Univ Iceland, Fac Med, Reykjavik, Iceland Show more [ 57 ] Mayo Clin, Dept Neurol, Rochester, MN USA Show more [ 58 ] Univ Mississippi, Med Ctr, Dept Data Sci, Jackson, MS 39216 USA Show more [ 59 ] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA Show more [ 60 ] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA Show more [ 61 ] Natl Ctr Global Hlth & Med, Res Inst, Dept Gene Diagnost & Therapeut, Tokyo, Japan Show more [ 62 ] Shimane Univ, Sch Med, Dept Internal Med 3, Matsue, Shimane, Japan Show more [ 63 ] Shimane Univ, Sch Med, Dept Funct Pathol, Matsue, Shimane, Japan Show more [ 64 ] Rush Univ, Med Ctr, Chicago, IL 60612 USA Show more [ 65 ] Brigham & Womens Hosp, Boston, MA 02115 USA Show more [ 66 ] Columbia Univ, Med Ctr, Ctr Translat & Computat Neuroimmunol, Dept Neurol, New York, NY USA [ 67 ] Kaiser Permanente Washington Hlth Res Inst, Seattle, WA USA Show more [ 68 ] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Los Angeles Biomed Res Inst, Torrance, CA 90509 USA Show more [ 69 ] Harbor UCLA Med Ctr, Div Genom Outcomes, Dept Pediat, Torrance, CA 90509 USA Show more [ 70 ] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA Show more [ 71 ] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA Show more [ 72 ] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA USA Show more [ 73 ] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA Show more [ 74 ] Singapore Eye Res Inst, Singapore, Singapore Show more [ 75 ] Duke NUS Grad Med Sch, Singapore, Singapore Show more [ 76 ] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore Show more [ 77 ] Natl Univ Hlth Syst, MACC, Singapore, Singapore Show more [ 78 ] Erasmus MC Univ Med Ctr, Genet Epidemiol Unit, Dept Epidemiol & Biostat, Rotterdam, Netherlands Show more [ 79 ] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA Show more [ 80 ] Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh, Midlothian, Scotland Show more [ 81 ] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh, Midlothian, Scotland Show more [ 82 ] Univ Edinburgh, Edinburgh Dementia Res Ctr, Edinburgh, Midlothian, Scotland Show more [ 83 ] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland Show more [ 84 ] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh, Midlothian, Scotland Show more [ 85 ] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland Show more [ 86 ] Univ Leuven, KU Leuven, Dept Neurosci, Expt Neurol, Leuven, Belgium Show more [ 87 ] Univ Leuven, KU Leuven, Leuven Res Inst Neurosci & Dis LIND, Leuven, Belgium Show more [ 88 ] VIB, Ctr Brain & Dis Res, Lab Neurobiol, Leuven, Belgium Show more [ 89 ] Univ Hosp Leuven, Dept Neurol, Leuven, Belgium Show more [ 90 ] Univ Melbourne, Florey Inst Neurosci & Mental Hlth, Melbourne, Vic, Australia Show more [ 91 ] Univ New South Wales, Ctr Hlth Brain Ageing, Psychiat, Sydney, NSW, Australia Show more [ 92 ] Univ New South Wales, Dementia Ctr Res Collaborat, Sydney, NSW, Australia Show more [ 93 ] Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia Show more [ 94 ] Murdoch Univ, Math & Stat, Perth, WA, Australia Show more [ 95 ] Neurosci Res Australia, Randwick, NSW, Australia Show more [ 96 ] Univ Sydney, Brain & Mind Ctr, Camperdown, NSW, Australia Show more [ 97 ] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia Show more [ 98 ] Natl Ageing Res Inst, Melbourne, Vic, Australia Show more [ 99 ] Univ Melbourne, Acad Unit Psychiat Old Age, Melbourne, Vic, Australia Show more [ 100 ] Fdn IRCCS Ist Neurol Carlo Besta, Dept Cerebrovasc Dis, Milan, Italy Show more [ 101 ] Univ Oxford, CTSU, Nuffield Dept Populat Hlth, Oxford, England Show more [ 102 ] Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England Show more [ 103 ] NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA Show more [ 104 ] Univ Glasgow, Inst Cardiovasc & Med Sci, Fac Med, Glasgow, Lanark, Scotland Show more [ 105 ] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland Show more [ 106 ] German Ctr Neurodegenerat Dis DZNE, Site Rostock, Greifswald, Germany Show more [ 107 ] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany Show more [ 108 ] John Hunter Hosp, Hunter Med Res Inst, Callaghan, NSW, Australia Show more [ 109 ] Univ Newcastle, Callaghan, NSW, Australia Show more [ 110 ] Hosp del Mar, IMIM, Dept Neurol, Neurovasc Res Grp NEU VAS, Barcelona, Spain Show more [ 111 ] Royal Holloway Univ London, Inst Cardiovasc Res, London, England [ 112 ] St Peters & Ashford Hosp, Chertsey, Surrey, England Show more [ 113 ] Harvard Med Sch, Ctr Human Genet Res, Massachusetts Gen Hosp, Program Med & Populat Genet,Broad Inst, Boston, MA 02115 USA Show more [ 114 ] Harvard Med Sch, Dept Neurol, Massachusetts Gen Hosp, Program Med & Populat Genet,Broad Inst, Boston, MA 02115 USA Show more [ 115 ] Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA Show more [ 116 ] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA [ 117 ] Baltimore VAMC, Baltimore, MD USA Show more [ 118 ] Mayo Clin Jacksonville, Dept Neurol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA Show more [ 119 ] Jagiellonian Univ, Dept Neurol, Krakow, Poland Show more [ 120 ] Lund Univ, Dept Clin Sci Lund, Neurol, Lund, Sweden Show more [ 121 ] Skane Univ Hosp, Dept Neurol & Rehabil Med, Malmo, Sweden Show more [ 122 ] Lund Univ, Dept Clin Sci Malmo, Lund, Sweden Show more [ 123 ] Seton Hall Univ, Neurosci Inst, Sch Hlth & Med Sci, St Francis Med Ctr, S Orange, NJ 07079 USA Show more [ 124 ] Univ Kentucky, Coll Publ Hlth, Lexington, KY USA Show more [ 125 ] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Gothenburg, Sweden Show more [ 126 ] Univ Florida, Dept Pharmacotherapy & Translat Res, Gainesville, FL USA Show more [ 127 ] Univ Florida, Ctr Pharmacogen, Coll Pharm, Gainesville, FL USA Show more [ 128 ] Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA Show more [ 129 ] Univ British Columbia, Dept Neurol, Vancouver, BC, Canada Show more [ 130 ] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA Show more [ 131 ] Washington Univ, Sch Med, Dept Neurol, Stroke Ctr, St Louis, MO 63110 USA Show more [ 132 ] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA Show more [ 133 ] Univ Virginia, Sch Med, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA [ 134 ] Netherlands Heart Inst, Durrer Ctr Cardiovasc Res, Utrecht, Netherlands Show more [ 135 ] UCL, Fac Populat Hlth Sci, Inst Cardiovasc Sci, London, England Show more [ 136 ] UCL, Farr Inst Hlth Informat Res, London, England Show more [ 137 ] UCL, Inst Hlth Informat, London, England Show more [ 138 ] Monash Univ, Monash Hlth, Peninsula Clin Sch, Melbourne, Vic, Australia Show more [ 139 ] Monash Univ, Monash Hlth, Frankston Hosp, Cent Clin Sch, Melbourne, Vic, Australia Show more [ 140 ] Monash Univ, Monash Hlth, Sch Clin Sci, Melbourne, Vic, Australia Show more [ 141 ] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia Show more [ 142 ] Western Sydney Univ, Penrith, NSW, Australia Show more [ 143 ] Univ Virginia, Dept Neurol, Charlottesville, VA USA Show more [ 144 ] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA [ 145 ] Prince Wales Hosp, Neuropsychiat Inst, Randwick, NSW, Australia Show more [ 146 ] Munich Cluster Syst Neurol SyNergy, Munich, Germany Show more [ 147 ] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA Show more [ 148 ] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA [ 149 ] Glenn Biggs Inst Alzheimers & Neurodegenerat Dis, San Antonio, TX USA (Lippincott Williams & Wilkins, 2019-01-16)
      To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.
    • Risk factors for chronic and recurrent pancreatitis after first attack of acute pancreatitis.

      Magnusdottir, Berglind A; Baldursdottir, Maria B; Kalaitzakis, Evangelos; Björnsson, Einar S; 1 a Faculty of Medicine , University of Iceland , Reykjavík , Iceland. 2 b Digestive Disease Center, Copenhagen University Hospital/Herlev, University of Copenhagen , Copenhagen , Denmark. 3 c Department of Gastroenterology , Landspitali University Hospital Reykjavik , Reykjavík , Iceland. (Taylor & Francis, 2019-01)
      To study the outcome of acute pancreatitis and risk factors for recurrent and chronic pancreatitis in a population based cohort of patients with first-time acute pancreatitis. All patients with first-time acute pancreatitis from 2006-2015 in Iceland were retrospectively evaluated. Medical records were scrutinized and relevant data extracted. 1102 cases of first-time acute pancreatitis were identified: mean age 56yr, 46% female, 41% biliary, 21% alcohol, 26% idiopathic, 13% other causes, mean follow-up 4yr. 21% had ≥1 recurrent acute pancreatitis which was independently related to alcoholic (vs. biliary hazard ratio (HR) 2.29, 95% confidence interval (CI) 1.51-3.46), male gender (HR 1.48, 95%CI 1.08-2.04), and smoking (HR 1.62, 95%CI 1.15-2.28). 3.7% developed chronic pancreatitis. Independent predictors were recurrent acute pancreatitis (HR 8.79, 95%CI 3.94-19.62), alcoholic (vs. biliary HR 9.16, 95%CI 2.71-30.9), local complications (HR 4.77, 95%CI 1.93-11.79), and organ-failure (HR 2.86, 95%CI 1.10-7.42). Recurrent acute pancreatitis occurred in one-fifth of patients. Development of chronic pancreatitis was infrequent. Both recurrent acute pancreatitis and chronic pancreatitis were related to alcoholic acute pancreatitis, while recurrent acute pancreatitis was associated with smoking and male gender, and chronic pancreatitis to recurrent acute pancreatitis, organ-failure, and local complications.
    • Gastroenteropancreatic neuroendocrine tumors in Iceland: a population-based study.

      Gudmundsdottir, Hallbera; Möller, Páll Helgi; Jonasson, Jon Gunnlaugur; Björnsson, Einar S; 1 a Department of Internal Medicine, Division of Gastroenterology , Landspitali University Hospital , Reykjavik , Iceland. 2 b Department of Surgery, Division of Abdominal Surgery , Landspitali University Hospital , Reykjavik , Iceland. 3 c Faculty of Medicine , University of Iceland , Reykjavik , Iceland. 4 d Department of Pathology , Landspitali University Hospital , Reykjavik , Iceland. (Taylor & Francis, 2019-01)
      To determine the incidence, distribution, and prognosis of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) over the last 30 years and analyze changes over time. All patients diagnosed with GEP-NETs in Iceland from 1985 to 2014 were identified through the Icelandic Cancer Registry and pathology laboratory records. Relevant clinical information was obtained from medical records. In order to assess trends, the study period was divided into two periods, 1985-1999 and 2000-2014. A total of 364 patients with GEP-NETs were identified. Overall, 18 patients diagnosed at autopsy or with primary tumors of an unknown site were excluded, leaving 346 patients with 351 primary tumors for final analysis. The overall mean annual incidence 1985-2014 was 3.65/100,000, 3.39/100,000 during 1985-1999 and 3.85/100,000 during 2000-2014 (p = NS). The most common primary tumor site was the appendix (32%), followed by the jejunum/ileum (24%) and stomach (17%). In all, 18% of patients presented with distant metastases at the time of diagnosis, most noticeably patients with primary tumors of the colon (47%), pancreas (46%) and jejunum/ileum (39%). The most favorable 5-year survival was observed for tumors of the appendix (94%) and rectum (88%) and the least favorable for tumors of the pancreas (31%), colon (47%) and jejunum/ileum (66%). There were no statistically significant changes in incidence, staging or survival between the two time periods. In this population-based study, the incidence of GEP-NETs has not changed significantly over the last decades. The incidence of metastatic disease has remained stable and overall prognosis has not improved in recent years.
    • A Global Comparison of Anatomic Risk Factors and Their Relationship to Obstructive Sleep Apnea Severity in Clinical Samples.

      Sutherland, Kate; Keenan, Brendan T; Bittencourt, Lia; Chen, Ning-Hung; Gislason, Thorarinn; Leinwand, Sarah; Magalang, Ulysses J; Maislin, Greg; Mazzotti, Diego R; McArdle, Nigel; Mindel, Jesse; Pack, Allan I; Penzel, Thomas; Singh, Bhajan; Tufik, Sergio; Schwab, Richard J; Cistulli, Peter A; 1 Department of Respiratory and Sleep Medicine, Royal North Shore Hospital, Sydney, New South Wales, Australia. 2 Charles Perkins Centre, Sydney Medical School, University of Sydney, Sydney, Australia. 3 Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia, Pennsylvania. 4 Disciplilna de Medicina e Biologia do Sono, Departamento de Psicobiologia, Universidade Federal de Sao Paulo, Sao Paulo, Brazil. 5 Sleep Center, Department of Pulmonary and Critical Care Medicine; Chang Gung Memorial Hospital, Taoyuan, Taiwan. 6 Department of Respiratory Medicine and Sleep, Landspitali -The National University Hospital of Iceland and Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 7 Division of Pulmonary, Critical Care, and Sleep Medicine, The Ohio State Wexner Medical Center, Columbus, Ohio. 8 Division of Sleep Medicine, Perelman School of Medicine at the University of Pennsylvania. 9 West Australian Sleep Disorders Research Institute; Department of Pulmonary Physiology and Sleep Medicine, Sir Charles Gairdner Hospital; University of Western Australia, Perth, Western Australia, Australia. 10 Center of Sleep Medicine, Charité University Hospital, Berlin, Germany. (American Academy of Sleep Medicine, 2019-04-15)
      Obstructive sleep apnea (OSA) is a global health issue and is associated with obesity and oropharyngeal crowding. Global data are limited on the effect of ethnicity and sex on these relationships. We compare associations between the apnea-hypopnea index (AHI) and these risk factors across ethnicities and sexes within sleep clinics. This is a cross-sectional, multicenter study of patients with OSA from eight sleep centers representing the Sleep Apnea Global Interdisciplinary Consortium (SAGIC). Four distinct ethnic groups were analyzed, using a structured questionnaire: Caucasians (Australia, Iceland, Germany, United States), African Americans (United States), Asians (Taiwan), and South Americans (Brazil). Regression analyses and interaction tests were used to assess ethnic and sex differences in relationships between AHI and anthropometric measures (body mass index [BMI], neck circumference, waist circumference) or Mallampati score. Analyses included 1,585 individuals from four ethnic groups: Caucasian (60.6%), African American (17.5%), Asian (13.1%), and South American (8.9%). BMI was most strongly associated with AHI in South Americans (7.8% increase in AHI per 1 kg/m We demonstrate ethnic and sex variations in associations between obesity and OSA. For similar BMI increases, South American patients show greatest AHI increases compared to African Americans. Findings highlight the importance of considering ethnicity and sex in clinical assessments of OSA risk.
    • Placental protein 13 (PP13) stimulates rat uterine vessels after slow subcutaneous administration.

      Drobnjak, Tijana; Jónsdóttir, Anna Margrét; Helgadóttir, Helga; Runólfsdóttir, Margrét Soffía; Meiri, Hamutal; Sammar, Marei; Osol, George; Mandalà, Maurizio; Huppertz, Berthold; Gizurarson, Sveinbjörn; 1 Faculty of Pharmaceutical Sciences, School of Health Science, University of Iceland, Reykjavik, Iceland, sveinbj@hi.is. 2 Department of Pathology, University Hospital Iceland, Reykjavik, Iceland. 3 Hy Laboratories Ltd, Rehovot, Israel. 4 TeleMarpe Ltd., Tel Aviv, Israel. 5 Ephraim Katzir Department of Biotechnology Engineering, ORT Braude College, Karmiel, Israel. 6 Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont College of Medicine, Burlington, VT, USA. 7 Department of Biology, Ecology and Earth Sciences, University of Calabria, Rende, Italy. 8 Department of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria. (Dove Medical Press, 2019-03)
      Reduced concentrations of placental protein 13 (PP13) during the first trimester of human pregnancy are associated with elevated risk for the subsequent development of preeclampsia, which is one of the deadliest obstetrical complications of pregnancy. Previous studies by our group have shown that PP13 lowers blood pressure in pregnant rats, increases the size and weight of pups and placentas, and induces vasodilation of resistance arteries through endothelial signaling pathways involving endothelial nitric oxid synthase and prostaglandin. In the present study, the effect of PP13 was investigated in nonpregnant female Sprague Dawley rats (n=27). Osmotic pumps were surgically implanted subcutaneously that released a constant dose of PP13 or saline over 7 days. Most animals were sacrificed 6 days after the end of PP13 release (on day 13), while some were sacrificed immediately at the end of day 7 (the last PP13 release day), to compare the short- and long-term impact of PP13 on vessels' growth and size. The uterine vessels were significantly expanded in the group exposed to recombinant PP13 (rPP13) compared to the control (saline) group. Both veins and arteries were significantly expanded by rPP13 with a more pronounced effect after 13 days compared to the corresponding vessels after 7 days. Furthermore, the long-term effect of treatment by rPP13 was more pronounced in the veins compared to the corresponding arteries. The effect of a PP13 variant with a histidine-tag (His-PP13) remained the same between 7 and 13 days. In conclusion, PP13 might play a key role in the expansive remodeling of the uterine vessels, reflecting what would happen if the rat was pregnant, preparing the uterine vascu-lature for the increase in uteroplacental blood flow, which is necessary for normal pregnancy. We suggest that PP13 could act by NO signaling pathways, a hypothesis that requires future study.
    • Postoperative Acute Kidney Injury: Focus on Renal Recovery Definitions, Kidney Disease Progression and Survival.

      Long, Thorir E; Helgadottir, Solveig; Helgason, Dadi; Sigurdsson, Gisli H; Gudbjartsson, Tomas; Palsson, Runolfur; Indridason, Olafur S; Sigurdsson, Martin I; 1 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2 Internal Medicine Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 3 Department of Anesthesia and Intensive Care, Akademiska University Hospital, Uppsala, Sweden. 4 Division of Anesthesia and Intensive Care Medicine, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 5 Division of Cardiothoracic Surgery, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 6 Division of Nephrology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 7 Faculty of Medicine, University of Iceland, Reykjavik, Iceland, martiningi@gmail.com. 8 Division of Anesthesia and Intensive Care Medicine, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland, martiningi@gmail.com. (Karger, 2019-01)
      The aim of this study was to examine different definitions of renal recovery following postoperative acute kidney injury (AKI) and how these definitions associate with survival and the development and progression of chronic kidney disease (CKD). This was a retrospective study of all patients who underwent abdominal, cardiothoracic, vascular, or orthopedic surgery at a single university hospital between 1998 and 2015. Recovery of renal function following postoperative AKI was assessed comparing 4 different definitions: serum creatinine (SCr) (i) < 1.1 × baseline, (ii) 1.1-1.25 × baseline, (iii) 1.25-1.5 × baseline, and (iv) > 1.5 × baseline. One-year survival and the development or progression of CKD within 5 years was compared with a propensity score-matched control groups. In total, 2,520 AKI patients were evaluated for renal recovery. Risk of incident and progressive CKD within 5 years was significantly increased if patients did not achieve a reduction in SCr to < 1.5 × baseline (hazard ratio [HR] 1.50; 95% CI 1.29-1.75) and if renal recovery was limited to a fall in SCr to 1.25-1.5 × baseline (HR 1.32; 95% CI 1.12-1.57) within 30 days. The definition of renal recovery that best predicted survival was a reduction in SCr to < 1.5 × baseline within 30 days. One-year survival of patients whose SCr decreased to < 1.5 × baseline within 30 days was significantly better than that of a propensity score-matched control group that did not achieve renal recovery (85 vs. 71%, p < 0.001). These findings should be considered when a consensus definition of renal recovery after AKI is established.
    • ARDS from miliary tuberculosis successfully treated with ECMO.

      Vesteinsdottir, Edda; Myrdal, Gunnar; Sverrisson, Kristinn O; Skarphedinsdottir, Sigurbjorg J; Gudlaugsson, Olafur; Karason, Sigurbergur; 1 Landspitali University Hospital, Department of Anaesthesia and Intensive Care, Hringbraut, 101, Reykjavik, Iceland. 2 Landspitali University Hospital, Department of Cardiothoracic Surgery, Hringbraut, 101, Reykjavik, Iceland. 3 Landspitali University Hospital, Department of Infectious Diseases, Fossvogi, 108, Reykjavik, Iceland. 4 University of Iceland, Faculty of Medicine, Vatnsmyrarvegi 16, 101, Reykjavik, Iceland. (Elsevier Science, 2019-01)
      Tuberculosis is a rare cause of acute respiratory distress syndrome (ARDS) and mortality rates are high in tuberculosis patients that need treatment with mechanical ventilation. Experience of the use of extracorporeal membrane oxygenation (ECMO) in such circumstances is scarce. We report the case of an 18 year old man where prolonged therapy (50 days) with extracorporeal membrane oxygenation (ECMO) allowed extensive lung damage from miliary tuberculosis to heal. The case reflects how challenging the diagnosis of tuberculosis may be and how difficult it is to reach adequate blood levels of anti-tuberculosis drugs while on ECMO. It's also an example of how indications for ECMO have been expanding the last years and that long term ECMO therapy is possible without serious complications.
    • Improved long-term survival following pulmonary resections for non-small cell lung cancer: results of a nationwide study from Iceland.

      Halldorsson, Hannes; Orrason, Andri Wilberg; Oskarsdottir, Gudrun Nina; Petursdottir, Astridur; Fridriksson, Bjorn Mar; Magnusson, Magnus Karl; Jonsson, Steinn; Gudbjartsson, Tomas; 1 Department of Cardiothoracic Surgery, Landspitali University Hospital, Reykjavik, Iceland. 2 Department of Pulmonology, Skåne University Hospital, Lund, Sweden. 3 Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 4 Department of Pulmonology, Landspitali University Hospital, Reykjavik, Iceland. (AME Publishing Company, 2019-03)
      We studied the outcome of pulmonary resection with curative intent for non-small cell lung cancer (NSCLC) in a nationwide study covering a 24-year period, focusing on survival. All patients who underwent pulmonary resection for NSCLC in Iceland in the period 1991-2014 were reviewed for demographics, TNM stage and survival. Median length of follow-up was 45 months. Three 8-year periods were compared, overall survival was estimated, and prognostic factors for survival were identified. Altogether, 652 surgical resections were performed on 644 individuals (52% females): 492 lobectomies (75%), 77 pneumonectomies (12%), and 83 sublobar resections (13%). Mean age increased from 65 to 68 yrs during the study period (P=0.002). The number of cases operated at stage IA increased substantially between the first and last periods (29% Survival of patients who have undergone pulmonary resection for NSCLC has improved significantly in Iceland. This may be explained by the increased number of patients diagnosed at lower stages and improved preoperative staging, with fewer understaged patients.
    • Clinical practice guideline on atraumatic (pencil-point) vs conventional needles for lumbar puncture: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

      Rehn, Marius; Chew, Michelle S; Olkkola, Klaus T; Sverrison, Kristinn Ö; Yli-Hankala, Arvi; Møller, Morten Hylander; 1 Pre-Hospital Division, Air Ambulance Department, Oslo University Hospital, Oslo, Norway. 2 The Norwegian Air Ambulance Foundation, Oslo, Norway. 3 Faculty of Health Sciences, University of Stavanger, Stavanger, Norway. 4 Department of Anaesthesia and Intensive Care, Medicine and Health, Linköping University, Linköping, Sweden. 5 Department of Anaesthesiology, Intensive Care and Pain Medicine, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. 6 Department of Anaesthesia and Intensive Care Medicine, Landspitali University Hospital, Reykjavík, Iceland. 7 Department of Anaesthesia, Tampere University Hospital, Tampere, Finland. 8 Faculty of Medicine and Life Sciences, University of Tampere, Tampere, Finland. 9 Department of Intensive Care, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark. (Wiley, 2019-04)
      The Scandinavian Society of Anaesthesiology and Intensive Care Medicine Clinical Practice Committee endorses the BMJ Rapid Recommendation clinical practice guideline on atraumatic (pencil-point) vs conventional needles for lumbar puncture. This includes the strong recommendation for the use of atraumatic needles for lumbar puncture in all patients regardless of age or indication.
    • Low burden of minimal residual disease prior to transplantation in children with very high risk acute lymphoblastic leukaemia: The NOPHO ALL2008 experience.

      Ifversen, Marianne; Turkiewicz, Dominik; Marquart, Hanne V; Winiarski, Jacek; Buechner, Jochen; Mellgren, Karin; Arvidson, Johan; Rascon, Jelena; Körgvee, Lenne-Triin; Madsen, Hans O; Abrahamsson, Jonas; Lund, Bendik; Jonsson, Olafur G; Heilmann, Carsten; Heyman, Mats; Schmiegelow, Kjeld; Vettenranta, Kim; 1 Department of Paediatric and Adolescent Medicine, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark. 2 Lund University Hospital, Lund, Sweden. 3 The Tissue Typing Laboratory, Department of Clinical Immunology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 4 Astrid Lindgren Children's Hospital and Clintec, Karolinska University Hospital, Huddinge, Stockholm, Sweden. 5 Department of Paediatric Haematology and Oncology, Oslo University Hospital, Oslo, Norway. 6 Institution for Clinical Sciences, Department of Paediatrics, Queen Silvia Children's Hospital, Gothenburg, Sweden. 7 Uppsala University Children's Hospital, Uppsala, Sweden. 8 Centre for Paediatric Oncology and Haematology, Children's Hospital, Vilnius University Hospital, Vilnius, Lithuania. 9 Tallin Children's Hospital, Tallin, Estonia. 10 Department of Paediatrics, St. Olavs University Hospital Trondheim, Trondheim, Norway. 11 Department of Clinical and Molecular Medicine, NTNU, Trondheim, Norway. 12 Landspitali University Hospital, Reykjavik, Iceland. 13 Childhood Cancer Research Unit, Karolinska Institute, Astrid Lindgren's Children's Hospital, Karolinska University Hospital, Stockholm, Sweden. 14 Institute of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. 15 Department of Paediatrics, University of Helsinki, Helsinki, Finland. (Wiley, 2019-03)
      The population-based Nordic/Baltic acute lymphoblastic leukaemia (ALL) Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol combined minimal residual disease (MRD)-driven treatment stratification with very intense first line chemotherapy for patients with high risk ALL. Patients with MRD >= 5% at end of induction or >= 10(-3) at end of consolidation or following two high risk blocks were eligible for haematopoietic cell transplantation (HCT) in first remission. After at least three high risk blocks a total of 71 children received HCT, of which 46 had MRD >= 5% at end of induction. Ten patients stratified to HCT were not transplanted; 12 received HCT without protocol indication. Among 69 patients with evaluable pre-HCT MRD results, 22 were MRD-positive, one with MRD >= 10(-3). After a median follow-up of 5 center dot 5 years, the cumulative incidence of relapse was 23 center dot 5% (95% confidence interval [CI]: 10 center dot 5-47 center dot 7) for MRD-positive versus 5 center dot 1% (95% CI: 1 center dot 3-19 center dot 2), P = 0 center dot 02) for MRD-negative patients. MRD was the only variable significantly associated with relapse (hazard ratio 9 center dot 1, 95% CI: 1 center dot 6-51 center dot 0, P = 0 center dot 012). Non-relapse mortality did not differ between the two groups, resulting in disease-free survival of 85 center dot 6% (95% CI: 75 center dot 4-97 center dot 2) and 67 center dot 4% (95% CI: 50 center dot 2-90 center dot 5), respectively. In conclusion, NOPHO block treatment efficiently reduced residual leukaemia which, combined with modern transplant procedures, provided high survival rates, also among pre-HCT MRD-positive patients.