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1. Excess mortality in patients with advanced chronic hepatitis C treated with long-term peginterferon

Author: Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, From the Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO ; Department of Internal Medicine, Saint Louis University School of Medicine; 1402 South Grand Blvd., St. Louis, MO 63104, New England Research Institutes, Watertown, MA, Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA ; Department of Medicine, Harvard Medical School, Boston, MA, Liver Institute of Virginia, Bon Secours Health System, Newport News, VA, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD ; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, Department of Medicine, University of Connecticut Health Center, Farmington, CT ; Carolinas Medical Center,Charlotte, NC, Division of Virology, Department of Laboratory Medicine, University of Washington, Seattle, WA, Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, Division of Gastroenterology, University of California, Irvine, Irvine, CA ; Gastroenterology Service, VA Long Beach Healthcare System, Long Beach, CA, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, Bisceglie, Adrian M., Stoddard, Anne M., Dienstag, Jules L., Shiffman, Mitchell L., Seeff, Leonard B., Bonkovsky, Herbert L., Morishima, Chihiro, Wright, Elizabeth C., Snow, Kristin K., Lee, William M., Fontana, Robert J., Morgan, Timothy R., Ghany, Marc G., Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, MI, From the Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO ; Department of Internal Medicine, Saint Louis University School of Medicine; 1402 South Grand Blvd., St. Louis, MO 63104, New England Research Institutes, Watertown, MA, Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA ; Department of Medicine, Harvard Medical School, Boston, MA, Liver Institute of Virginia, Bon Secours Health System, Newport News, VA, Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD ; Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, Department of Medicine, University of Connecticut Health Center, Farmington, CT ; Carolinas Medical Center,Charlotte, NC, Division of Virology, Department of Laboratory Medicine, University of Washington, Seattle, WA, Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, Division of Gastroenterology, University of California, Irvine, Irvine, CA ; Gastroenterology Service, VA Long Beach Healthcare System, Long Beach, CA, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, Bisceglie, Adrian M., Stoddard, Anne M., Dienstag, Jules L., Shiffman, Mitchell L., Seeff, Leonard B., Bonkovsky, Herbert L., Morishima, Chihiro, Wright, Elizabeth C., Snow, Kristin K., Lee, William M., Fontana, Robert J., Morgan, Timothy R., and Ghany, Marc G.
Abstract: Chronic hepatitis C virus infection can cause chronic liver disease, cirrhosis and liver cancer. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial was a prospective, randomized controlled study of long-term, low-dose peginterferon therapy in patients with advanced chronic hepatitis C who failed to respond to a previous course of optimal antiviral therapy. The aim of this follow-up analysis is to describe the frequency and causes of death among this cohort of patients. Deaths occurring during and after the HALT-C Trial were reviewed by a committee of investigators to determine the cause of death and to categorize each death as liver- or nonliver-related and as related or not to complications of peginterferon. Rates of liver transplantation were also assessed. Over a median of 5.7 years, 122 deaths occurred among 1,050 randomized patients (12%), of which 76 were considered liver-related (62%) and 46 nonliver-related (38%); 74 patients (7%) underwent liver transplantation. At 7 years the cumulative mortality rate was higher in the treatment compared to the control group (20% versus 15%, P = 0.049); the primary difference in mortality was in patients in the fibrosis compared to the cirrhosis stratum (14% versus 7%, P = 0.01); comparable differences were observed when liver transplantation was included. Excess mortality, emerging after 3 years of treatment, was related largely to nonliver-related death; liver-related mortality was similar in the treatment and control groups. No specific cause of death accounted for the excess mortality and only one death was suspected to be a direct complication of peginterferon. Conclusion: Long-term maintenance peginterferon in patients with advanced chronic hepatitis C is associated with an excess overall mortality, which was primarily due to nonliver-related causes among patients with bridging fibrosis. (H EPATOLOGY 2011;)
Published: 2011

2. Systematic Review on the Management of Chronic Constipation in North America

Author: Division of Gastroenterology, University of Michigan School of Medicine, and Center for Excellence in Health Services Research, Veterans Affairs Medical Center, Ann Arbor, MI, Division of Gastroenterology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, Division of Gastroenterology, Saint Louis University School of Medicine, St. Louis, MO, Department of Medicine and Alimentary Pharmabiotic Center, National University of Ireland, Cork, Ireland, Division of Gastroenterology, Baylor University Medical Center, Dallas, TX, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, Brandt, Lawrence J., Prather, Charlene M., Quigley, Eamonn M. M., Schiller, Lawrence R., Schoenfeld, Philip, Talley, Nicholas J., Division of Gastroenterology, University of Michigan School of Medicine, and Center for Excellence in Health Services Research, Veterans Affairs Medical Center, Ann Arbor, MI, Division of Gastroenterology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, Division of Gastroenterology, Saint Louis University School of Medicine, St. Louis, MO, Department of Medicine and Alimentary Pharmabiotic Center, National University of Ireland, Cork, Ireland, Division of Gastroenterology, Baylor University Medical Center, Dallas, TX, Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, Brandt, Lawrence J., Prather, Charlene M., Quigley, Eamonn M. M., Schiller, Lawrence R., Schoenfeld, Philip, and Talley, Nicholas J.
Published: 2010

3. Outcome of sustained virological responders with histologically advanced chronic hepatitis C

Author: Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI, Division of Gastroenterology, University of California Irvine, Irvine, CA ; Gastroenterology Service, Veterans Affairs Long Beach Healthcare System, Long Beach, CA ; fax: 562-826-5436 ; VA Long Beach Healthcare System???11 (GI), 5901 East Seventh Street, Long Beach, CA 90822, Liver Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, New England Research Institutes, Watertown, MA, Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA, Division of Gastroenterology and Hepatology, University of Colorado at Denver and Health Sciences Center, Denver, CO, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO, Departments of Medicine and Molecular and Structural Biology and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, and the Department of Medicine, Harvard Medical School, Boston, MA, Division of Virology, Department of Laboratory Medicine, University of Washington, Seattle, WA, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, Morgan, Timothy R., Ghany, Marc G., Kim, Hae-Young, Snow, Kristin K., Shiffman, Mitchell L., De Santo, Jennifer L., Lee, William M., Di Bisceglie, Adrian M., Bonkovsky, Herbert L., Dienstag, Jules L., Morishima, Chihiro, Lindsay, Karen L., Lok, Anna S. F., Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI, Division of Gastroenterology, University of California Irvine, Irvine, CA ; Gastroenterology Service, Veterans Affairs Long Beach Healthcare System, Long Beach, CA ; fax: 562-826-5436 ; VA Long Beach Healthcare System???11 (GI), 5901 East Seventh Street, Long Beach, CA 90822, Liver Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, New England Research Institutes, Watertown, MA, Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA, Division of Gastroenterology and Hepatology, University of Colorado at Denver and Health Sciences Center, Denver, CO, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO, Departments of Medicine and Molecular and Structural Biology and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, and the Department of Medicine, Harvard Medical School, Boston, MA, Division of Virology, Department of Laboratory Medicine, University of Washington, Seattle, WA, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, Morgan, Timothy R., Ghany, Marc G., Kim, Hae-Young, Snow, Kristin K., Shiffman, Mitchell L., De Santo, Jennifer L., Lee, William M., Di Bisceglie, Adrian M., Bonkovsky, Herbert L., Dienstag, Jules L., Morishima, Chihiro, Lindsay, Karen L., and Lok, Anna S. F.
Abstract: Retrospective studies suggest that subjects with chronic hepatitis C and advanced fibrosis who achieve a sustained virological response (SVR) have a lower risk of hepatic decompensation and hepatocellular carcinoma (HCC). In this prospective analysis, we compared the rate of death from any cause or liver transplantation, and of liver-related morbidity and mortality, after antiviral therapy among patients who achieved SVR, virologic nonresponders (NR), and those with initial viral clearance but subsequent breakthrough or relapse (BT/R) in the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) Trial. Laboratory and/or clinical outcome data were available for 140 of the 180 patients who achieved SVR. Patients with nonresponse (NR; n = 309) or who experienced breakthrough or relapse (BT/R; n = 77) were evaluated every 3 months for 3.5 years and then every 6 months thereafter. Outcomes included death, liver-related death, liver transplantation, decompensated liver disease, and HCC. Median follow-up for the SVR, BT/R, and NR groups of patients was 86, 85, and 79 months, respectively. At 7.5 years, the adjusted cumulative rate of death/liver transplantation and of liver-related morbidity/mortality in the SVR group (2.2% and 2.7%, respectively) was significantly lower than that of the NR group (21.3% and 27.2%, P < 0.001 for both) but not the BT/R group (4.4% and 8.7%). The adjusted hazard ratio (HR) for time to death/liver transplantation (HR = 0.17, 95% confidence interval [CI] = 0.06-0.46) or development of liver-related morbidity/mortality (HR = 0.15, 95% CI = 0.06-0.38) or HCC (HR = 0.19, 95% CI = 0.04-0.80) was significant for SVR compared to NR. Laboratory tests related to liver disease severity improved following SVR. Conclusion: Patients with advanced chronic hepatitis C who achieved SVR had a marked reduction in death/liver transplantation, and in liver-related morbidity/mortality, although they remain at risk for HCC. (H EPATOLOGY 2010;)
Published: 2010

4. Variants in interferon-alpha pathway genes and response to pegylated interferon-Alpha2a plus ribavirin for treatment of chronic hepatitis C virus infection in the hepatitis C antiviral long-term treatment against cirrhosis trial

Author: Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, Division of Gastroenterology, University of California - Irvine, Irvine, CA, and Gastroenterology Service, VA Long Beach Healthcare System, Long Beach, CA, Departments of Medicine and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, and Carolinas Medical Center, Charlotte, NC, New England Research Institutes, Watertown, MA, Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, Core Genotyping Facility, NCI/Division of Cancer Epidemiology and Genetics, Advanced Technology Program, SAIC-Frederick Inc., NCI-Frederick, Frederick, MD, Department of Medicine, Johns Hopkins University, Baltimore, MD, Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick Inc., NCI-Frederick Inc., Frederick, MD, Computer Sciences Corp., Rockville, MD, Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, Virology Division, Department of Laboratory Medicine, University of Washington, Seattle, WA, Gastrointestinal Unit, Medical Services, Massachusetts General Hospital, and the Department of Medicine, Harvard Medical School, Boston, MA, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD ; fax: 301-480-1917. ; 6120 Executive Boulevard, Room 6111, MSC 7246, Rockville, MD 20892, Welzel, Tania Mara, Morgan, Timothy R., Bonkovsky, Herbert L., Naishadham, Deepa, Pfeiffer, Ruth M., Wright, Elizabeth C., Hutchinson, Amy A., Crenshaw, Andrew T., Bashirova, Arman, Carrington, Mary, Dotrang, Myhanh, Sterling, Richard K., Lindsay, Karen L., Fontana, Robert J., Lee, William M., Di Bisceglie, Adrian M., Ghany, Marc G., Gretch, David R., Chanock, Stephen J., Chung, Raymond T., O'Brien, Thomas R., Division of Gastroenterology, University of Michigan Medical Center, Ann Arbor, MI, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, Division of Gastroenterology, University of California - Irvine, Irvine, CA, and Gastroenterology Service, VA Long Beach Healthcare System, Long Beach, CA, Departments of Medicine and The Liver-Biliary-Pancreatic Center, University of Connecticut Health Center, Farmington, CT, and Carolinas Medical Center, Charlotte, NC, New England Research Institutes, Watertown, MA, Office of the Director, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, Core Genotyping Facility, NCI/Division of Cancer Epidemiology and Genetics, Advanced Technology Program, SAIC-Frederick Inc., NCI-Frederick, Frederick, MD, Department of Medicine, Johns Hopkins University, Baltimore, MD, Cancer and Inflammation Program, Laboratory of Experimental Immunology, SAIC-Frederick Inc., NCI-Frederick Inc., Frederick, MD, Computer Sciences Corp., Rockville, MD, Hepatology Section, Virginia Commonwealth University Medical Center, Richmond, VA, Division of Gastrointestinal and Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, CA, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, TX, Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO, Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, Virology Division, Department of Laboratory Medicine, University of Washington, Seattle, WA, Gastrointestinal Unit, Medical Services, Massachusetts General Hospital, and the Department of Medicine, Harvard Medical School, Boston, MA, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD ; fax: 301-480-1917. ; 6120 Executive Boulevard, Room 6111, MSC 7246, Rockville, MD 20892, Welzel, Tania Mara, Morgan, Timothy R., Bonkovsky, Herbert L., Naishadham, Deepa, Pfeiffer, Ruth M., Wright, Elizabeth C., Hutchinson, Amy A., Crenshaw, Andrew T., Bashirova, Arman, Carrington, Mary, Dotrang, Myhanh, Sterling, Richard K., Lindsay, Karen L., Fontana, Robert J., Lee, William M., Di Bisceglie, Adrian M., Ghany, Marc G., Gretch, David R., Chanock, Stephen J., Chung, Raymond T., and O'Brien, Thomas R.
Abstract: Combination treatment with pegylated-interferon-alpha (PEG IFN-??) and ribavirin, the current recommended therapy for chronic hepatitis C virus (HCV) infection, results in a sustained virological response (SVR) in only about half of patients. Because genes involved in the interferon-alpha pathway may affect antiviral responses, we analyzed the relationship between variants in these genes and SVR among participants in the Hepatitis C Antiviral Long-Term treatment Against Cirrhosis (HALT-C) trial. Patients had advanced chronic hepatitis C that had previously failed to respond to interferon-based treatment. Participants were treated with peginterferon-??2a and ribavirin during the trial. Subjects with undetectable HCV RNA at week 72 were considered to have had an SVR. Subjects with detectable HCV RNA at week 20 were considered nonresponders. We used TaqMan assays to genotype 56 polymorphisms found in 13 genes in the interferon-alpha pathway. This analysis compares genotypes for participants with an SVR to nonresponders. The primary analysis was restricted to European American participants because a priori statistical power was low among the small number (n = 131) of African American patients. We used logistic regression to control the effect of other variables that are associated with treatment response. Among 581 European American patients, SVR was associated with IFNAR1 IVS1-22G (adjusted odds ratio, 0.57; P = 0.02); IFNAR2 Ex2-33C (adjusted odds ratio, 2.09; P = 0.02); JAK1 IVS22+112T (adjusted odds ratio, 1.66; P = 0.04); and ADAR Ex9+14A (adjusted odds ratio, 1.67; P = 0.03). For the TYK2 -2256A promoter region variant, a borderline association was present among European American participants (OR, 1.51; P = 0.05) and a strong relationship among African American patients; all 10 with SVR who were genotyped for TYK2 -2256 carried the A variant compared with 68 of 120 (57%) nonresponders ( P = 0.006). Conclusion: Genetic polymorphisms in the interferon-?? pathway may
Published: 2009

5. Differentiation of COVID-19 signs and symptoms from allergic rhinitis and common cold: An ARIA-EAACI-GA

Author: Jere Reijula, De Yun Wang, Ralph Mösges, Tomohisa Iinuma, Jean Luc Fauquert, Nelson Rosario, Yehia El-Gamal, René Maximiliano Gómez, Tari Haahtela, Vincenzo Patella, Lorenzo Cecchi, Petr Panzner, Yoshitaka Okamoto, Oliver Pfaar, Luis Caraballo, Paulo Augusto Moreira Camargos, Filip Raciborski, Florin Mihaltan, Ken Ohta, Brian J. Lipworth, Kimi Okubo, Juan Carlos Ivancevich, Fulvio Braido, Ioana Agache, Frederico S. Regateiro, Neven Miculinic, Tuula Vasankari, R. Emuzyte, Arunas Valiulis, Yousser Mohammad, Torsten Zuberbier, Osman M. Yusuf, Ewa Jassem, Cezmi A. Akdis, Jean Bousquet, Alessandro Fiocchi, Jan Hagemann, Claus Bachert, Davor Plavec, K. S. Bennoor, Marek Jutel, Désirée Larenas-Linnemann, Stephen Montefort, Stefano Del Giacco, Przemyslaw Kardas, Erkka Valovirta, Mark S. Dykewicz, Antonio Valero, Wienczyslawa Czarlewski, Thomas B. Casale, Gabrielle L. Onorato, Omer Kalayci, Ludger Klimek, Joaquin Sastre, João Fonseca, Siân Williams, Karl Christian Bergmann, Marek Niedoszytko, Bilun Gemicioglu, Mario E. Zernotti, Musa Khaitov, H. Neffen, Robert M. Naclerio, Joaquim Mullol, Ana Pereira, Piotr Kuna, Michael Makris, Maria Teresa Ventura, Ioanna Tsiligianni, Dirceu Solé, Arzu Yorgancioglu, Charlotte Suppli-Ulrik, M. Gotua, Emmanuel P. Prokopakis, Dana Wallace, Jorge Maspero, Wytske Fokkens, Eckard Hamelmann, Antonino Romano, Dejan Dokic, Todor A. Popov, Violeta Kvedariene, Derek K. Chu, Anna Bedbrook, Dermot Ryan, Motohiro Ebisawa, Tomas Chivato, Giovanni Passalacqua, Menachem Rottem, Mário Morais-Almeida, Victoria Cardona, Bolesław Samoliński, Cristiana Stellato, Nikolaos G. Papadopoulos, Milan Sova, Jaime Correia-de-Sousa, Sietze Reitsma, Cemal Cingi, Francesca Puggioni, Robyn E O'Hehir, HUS Inflammation Center, Department of Dermatology, Allergology and Venereology, HUS Internal Medicine and Rehabilitation, Department of Public Health, Clinicum, Keuhkosairauksien yksikkö, Helsinki University Hospital Area, University of Helsinki, University Medical Center of the Johannes Gutenberg-University Mainz, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Wrocław [Poland] (UWr), Swiss Institute of Allergy and Asthma Research (SIAF), Universität Zürich [Zürich] = University of Zurich (UZH), Transilvania University of Brasov, Humboldt University Of Berlin, Medical Consulting Czarlewski, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), MASK-air, Ghent University Hospital, Sun Yat-Sen University [Guangzhou] (SYSU), Karolinska Institutet [Stockholm], National Institute of Diseases of the Chest and Hospital (NIDCH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Ospedale Policlinico San Martino [Genoa], Universidade Federal de Minas Gerais = Federal University of Minas Gerais [Belo Horizonte, Brazil] (UFMG), University of Cartagena, Foundation for the Development of Medical and Biological Sciences (FUNDEMEB), Vall d'Hebron University Hospital [Barcelona], Allergy Unit [Malaga, Spain] (National Network ARADyAL), Hospital Regional Universitario de Málaga = Regional University Hospital of Malaga [Spain], University of South Florida [Tampa] (USF), Azienda Usl Toscana centro [Firenze], CEU-San Pablo University and HM-Hospitals School of Medicine, McMaster University [Hamilton, Ontario], Eskisehir Osmangazi University, Universidade do Minho = University of Minho [Braga], Life and Health Sciences Research Institute [Braga] (ICVS), University of Minho [Braga], The International Primary Care Respiratory Group (IPCRG), Università degli Studi di Cagliari = University of Cagliari (UniCa), Sts. Cyril and Methodius University, Saint Louis University School of Medicine [St Louis], Sagamihara National Hospital [Kanagawa, Japan], Ain Shams University (ASU), Vilnius University [Vilnius], Service de Pédiatrie Générale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Bambino Gesù Children’s Hospital [Rome, Italy], Academic Medical Center - Academisch Medisch Centrum [Amsterdam] (AMC), University of Amsterdam [Amsterdam] (UvA), European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Center of Research in Health Technologies and Information Systems (CINTESIS), Universidade do Porto = University of Porto, CUF Porto Hospital, Cerrahpasa Faculty of Medicine, Istanbul University, ALAS Medical Institute, Center for Allergy and Immunology Research [Tbilisi], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Universität Bielefeld = Bielefeld University, Chiba University Hospital, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Medical University of Gdańsk, Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Medical University of Łódź (MUL), Federal Medicobiological Agency [Moscow, Russian Federation], Hospital Medica Sur [Mexico City, Mexico], Ninewells Hospital and Medical School [Dundee], University General Hospital ' Attikon ' [Athens, Greece], Argentine Association of Allergy and Immunology, Marius Nasta Institute of Pneumology, Tishreen University, Université de Damas = Damascus University, University of Malta [Malta], Hospital CUF Descobertas, Clinical Research International Ltd [Hamburg, Germany] (CRI), Johns Hopkins University School of Medicine [Baltimore], Nemours/Alfred I. du Pont Hospital for Children, Monash University [Melbourne], Tokyo National Hospital, Nippon Medical School [Tokyo, Japon], Medicine Charles University and General Faculty Hospital in Prague, Royal Manchester Children's Hospital, University of Manchester [Manchester], Università degli studi di Genova = University of Genoa (UniGe), 'Santa Maria della Speranza' Hospital, Philipps Universität Marburg = Philipps University of Marburg, J.J. Strossmayer University of Osijek, Children’s Hospital Srebrnjak [Zagreb, Croatia], St. Ivan Rilski University Hospital, University of Crete [Heraklion] (UOC), IRCCS Humanitas [Rozzano, Italy], Medical University of Warsaw - Poland, Centro Hospitalar e Universitário [Coimbra], Amsterdam UMC - Amsterdam University Medical Center, Istituto di Ricovero e Cura a Carattere Scientifico [Troina, Italy] (IRCCS), Oasi Maria Santissima Srl [Troina, Italy], Clinica G.B. Morgagni (Fondazione Mediterranea), Pontifical Catholic University of Paraná (PUCPR), Pontifícia Universidade Católica do Paraná (PUCPR), Ha’Emek Medical Center [Afula, Israel], Pediatric Endocrine Institute [Afula, Israel], Usher Institute of Population Health Sciences and Informatics [Edinburgh, U.K.], University of Edinburgh, Federal University of Sao Paulo (Unifesp), University Hospital Olomouc [Czech Republic], University of Salerno (UNISA), Copenhagen University Hospital, Universitat de Barcelona (UB), European Academy of Paediatrics (EAP/UEMS-SP), University of Turku, Suomen Terveystalo Allergy Clinic, Finnish Lung Health Association, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), Nova Southeastern University (NSU), Yong Loo Lin School of Medicine [Singapore], Department of Biology, Faculty of Sciences & Liberal Arts, Celal Bayar University, Manisa Celal Bayar University, The Allergy & Asthma Institute, Pakistan (IPCRG), Universidad Nacional de Villa María, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Allergiezentrum Wiesbaden, Salvy-Córdoba, Nathalie, Ear, Nose and Throat, and AII - Inflammatory diseases
Subjects: 0301 basic medicine, Allergy, MESH: Asthma, Common Cold, allergic rhinitis, common cold, cough, COVID-19, smell, Consensus, Humans, SARS-CoV-2, Asthma, Rhinitis, Allergic, Disease, Care, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, MESH: COVID-19, Rhinitis, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Common cold, 3. Good health, MESH: Rhinitis, Allergic, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Original Article, medicine.symptom, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Immunology, Signs and symptoms, Asymptomatic, 03 medical and health sciences, Allergic, COVID‐19, Internal medicine, medicine, MESH: SARS-CoV-2, MESH: Consensus, MESH: Humans, business.industry, Rhinitis, Sinusitis, and Upper Airway Disease, CARE, medicine.disease, 030104 developmental biology, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 3121 General medicine, internal medicine and other clinical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, ORIGINAL ARTICLES, Airway, business, MESH: Common Cold
Abstract: Background Although there are many asymptomatic patients, one of the problems of COVID-19 is early recognition of the disease. COVID-19 symptoms are polymorphic and may include upper respiratory symptoms. However, COVID-19 symptoms may be mistaken with the common cold or allergic rhinitis. An ARIA-EAACI study group attempted to differentiate upper respiratory symptoms between the three diseases. Methods A modified Delphi process was used. The ARIA members who were seeing COVID-19 patients were asked to fill in a questionnaire on the upper airway symptoms of COVID-19, common cold and allergic rhinitis. Results Among the 192 ARIA members who were invited to respond to the questionnaire, 89 responded and 87 questionnaires were analysed. The consensus was then reported. A two-way ANOVA revealed significant differences in the symptom intensity between the three diseases (p < .001). Conclusions This modified Delphi approach enabled the differentiation of upper respiratory symptoms between COVID-19, the common cold and allergic rhinitis. An electronic algorithm will be devised using the questionnaire.
Published: 2021
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6. TDP-43 dysfunction results in R-loop accumulation and DNA replication defects

Author: Yuna M. Ayala, Alessandro Vindigni, Matthew D. Wood, Yea-Lih Lin, Albert A. Davis, Annabel Quinet, Philippe Pasero, Saint Louis University School of Medicine [St Louis], Institut de génétique humaine (IGH), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Genome instability, DNA Replication, R-loop, DNA damage, TDP-43, [SDV]Life Sciences [q-bio], Biology, TARDBP, 03 medical and health sciences, 0302 clinical medicine, mental disorders, medicine, Humans, Viability assay, Amyotrophic lateral sclerosis, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, RNA:DNA hybrids, Amyotrophic Lateral Sclerosis, DNA replication, nutritional and metabolic diseases, Cell Biology, R-loops, medicine.disease, Cell biology, nervous system diseases, DNA-Binding Proteins, Frontotemporal Dementia, R-Loop Structures, 030217 neurology & neurosurgery, Frontotemporal dementia, Research Article
Abstract: TAR DNA-binding protein 43 (TDP-43; also known as TARDBP) is an RNA-binding protein whose aggregation is a hallmark of the neurodegenerative disorders amyotrophic lateral sclerosis and frontotemporal dementia. TDP-43 loss increases DNA damage and compromises cell viability, but the actual function of TDP-43 in preventing genome instability remains unclear. Here, we show that loss of TDP-43 increases R-loop formation in a transcription-dependent manner and results in DNA replication stress. TDP-43 nucleic-acid-binding and self-assembly activities are important in inhibiting R-loop accumulation and preserving normal DNA replication. We also found that TDP-43 cytoplasmic aggregation impairs TDP-43 function in R-loop regulation. Furthermore, increased R-loop accumulation and DNA damage is observed in neurons upon loss of TDP-43. Together, our findings indicate that TDP-43 function and normal protein homeostasis are crucial in maintaining genomic stability through a co-transcriptional process that prevents aberrant R-loop accumulation. We propose that the increased R-loop formation and genomic instability associated with TDP-43 loss are linked to the pathogenesis of TDP-43 proteinopathies. This article has an associated First Person interview with the first author of the paper., Summary: TDP-43 deficiency increases the transcription-dependent accumulation of R-loops and perturbs DNA replication in proliferating cells. This R-loop accumulation, in turn, compromises genomic integrity in human cells, including neurons.
Published: 2020
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7. Intracellular localization of varicella-zoster virus ORF39 protein and its functional relationship to glycoprotein K

Author: Heineman, Thomas [Division of Infectious Diseases and Immunology, Saint Louis University School of Medicine, St. Louis, MO 63110-0250 (United States)]
Published: 2007
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8. Herpes simplex virus 2 VP22 phosphorylation induced by cellular and viral kinases does not influence intracellular localization

Author: Morrison, Lynda [Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, St. Louis, MO 63104-1083 (United States)]
Published: 2004
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9. Plasma Aβ and neurofilament light chain are associated with cognitive and physical function decline in non-dementia older adults

Author: He, L., Souto Barreto, P., Aggarwal, G., Nguyen, A. D., Morley, J. E., Li, Y., Bateman, R. J., Vellas, B., Bonnefoy, M., Gabelle, Audrey, Gérontopôle, Epidémiologie et analyses en santé publique : risques, maladies chroniques et handicaps (LEASP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Saint Louis University School of Medicine [St Louis], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), MAPT/DSA Group: Bruno Vellas, Sophie Guyonnet, Isabelle Carrié, Lauréane Brigitte, Catherine Faisant, Françoise Lala, Julien Delrieu, Hélène Villars, Emeline Combrouze, Carole Badufle, Audrey Zueras, Sandrine Andrieu, Christelle Cantet, Christophe Morin, Gabor Abellan Van Kan, Charlotte Dupuy, Yves Rolland, Céline Caillaud, Pierre-Jean Ousset, Françoise Lala, Sherry Willis, Sylvie Belleville, Brigitte Gilbert, Jean-François Dartigues, Isabelle Marcet, Fleur Delva, Alexandra Foubert, Sandrine Cerda, Corinne Costes, Olivier Rouaud, Patrick Manckoundia, Valérie Quipourt, Sophie Marilier, Evelyne Franon, Lawrence Bories, Marie-Laure Pader, Marie-France Basset, Bruno Lapoujade, Valérie Faure, Michael Li Yung Tong, Christine Malick-Loiseau, Evelyne Cazaban-Campistron, Françoise Desclaux, Colette Blatge, Thierry Dantoine, Cécile Laubarie-Mouret, Isabelle Saulnier, Jean-Pierre Clément, Marie-Agnès Picat, Laurence Bernard-Bourzeix, Stéphanie Willebois, Iléana Désormais, Noëlle Cardinaud, Marc Bonnefoy, Pierre Livet, Pascale Rebaudet, Claire Gédéon, Catherine Burdet, Flavien Terracol, Alain Pesce, Stéphanie Roth, Sylvie Chaillou, Sandrine Louchart, Kristelle Sudres, Nicolas Lebrun, Nadège Barro-Belaygues, Jacques Touchon, Karim Bennys, Audrey Gabelle, Aurélia Romano, Lynda Touati, Cécilia Marelli, Cécile Pays, Philippe Robert, Franck Le Duff, Claire Gervais, Sébastien Gonfrier, Yannick Gasnier, Serge Bordes, Danièle Begorre, Christian Carpuat, Khaled Khales, Jean-François Lefebvre, Samira Misbah El Idrissi, Pierre Skolil, Jean-Pierre Salles, Carole Dufouil, Stéphane Lehéricy, Marie Chupin, Jean-François Mangin, Ali Bouhayia, Michèle Allard, Frédéric Ricolfi, Dominique Dubois, Marie Paule Bonceour Martel, François Cotton, Alain Bonafé, Stéphane Chanalet, Françoise Hugon, Fabrice Bonneville, Christophe Cognard, François Chollet, Pierre Payoux, Thierry Voisin, Julien Delrieu, Sophie Peiffer, Anne Hitzel, Michèle Allard, Michel Zanca, Jacques Monteil, Jacques Darcourt, Laurent Molinier, Hélène Derumeaux, Nadège Costa, Bertrand Perret, Claire Vinel, Sylvie Caspar-Bauguil, Pascale Olivier-Abbal, Sandrine Andrieu, Christelle Cantet, Nicola Coley, CarMeN, laboratoire, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Toulouse [Toulouse], Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), and Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM)
Subjects: medicine.medical_specialty, Neurology, Cognitive Neuroscience, Neurofilament light, [SDV]Life Sciences [q-bio], Intermediate Filaments, Physical function, Audiology, Neurofilament light chain, lcsh:RC346-429, lcsh:RC321-571, 03 medical and health sciences, Cognition, 0302 clinical medicine, Humans, Medicine, Dementia, Amyloid-β, Cognitive Dysfunction, Prospective Studies, lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry, lcsh:Neurology. Diseases of the nervous system, Aged, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, Amyloid beta-Peptides, business.industry, Research, Cognitive function, medicine.disease, Cognitive training, Cognitive test, [SDV] Life Sciences [q-bio], Cross-Sectional Studies, Neurology (clinical), business, Body mass index, 030217 neurology & neurosurgery
Abstract: BackgroundCognition is closely associated with physical function. Although high brain amyloid-β (Aβ) deposition and neurofilament light chain (NfL) are associated with cognitive and gait speed decline, relationships of combined plasma Aβ and NfL profiles with cognitive and physical functions in older adults remain unknown. The research aim of this study was to investigate the prospective associations of combined plasma Aβ and NfL profiles with cognitive and physical functions in older adults.MethodsParticipants (n = 452, aged 76 ± 5 years) who had both plasma Aβ and NfL data collected from the Multidomain Alzheimer’s Preventive Trial (MAPT, May 2008 to April 2016) were included in the current study. These participants were from four MAPT groups (multidomain interventions [physical activity and nutritional counselling, and cognitive training], omega-3 supplementation, multidomain plus omega-3 supplementation and control group) and had received a 3-year intervention, followed by a 2-year observational follow-up. Cognitive function was evaluated as Mini-Mental State Examination and composite cognitive score (CCS, a meanZ-score combining four cognitive tests). Physical function was evaluated as gait speed (4-m usual-pace walk test) and chair-stand time (5-time maximal chair-stand test). Cognitive and physical function data measured at the time of and after blood Aβ and NfL tests were used for analysis. Participants with plasma Aβ42/Aβ40ratios lower than 0.107 and NfL levels greater than 93.04 pg/ml were classified as Aβ+ and NfL+. Multivariable regressions and mixed-effects linear models were used for the analysis.ResultsAt the cross-sectional level, no significant association was found between Aβ+NfL+ and cognitive or physical function after controlling for age, sex, body mass index, education level and MAPT group. Evaluating longitudinal changes, participants with Aβ+NfL+ had greater annual declines in the CCS (β = − 0.11, 95%CI [− 0.17, − 0.05]) and gait speed (β = − 0.03, 95%CI [− 0.05, − 0.005]). After adjusting for APOE ɛ4 genotype, Aβ+NfL+ was associated with a greater decline only in the CCS (β = − 0.09, 95%CI [− 0.15, − 0.02]).ConclusionsCombined low plasma Aβ42/Aβ40ratio and high plasma NfL level was associated with greater declines in cognition and gait speed over time, providing further evidence of the links between cognitive and physical function.Trial registrationwww.clinicaltrials.gov[NCT00672685].
Published: 2020
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10. 2019 ARIA Care pathways for allergen immunotherapy

Author: Dana Wallace, Karin C. Lødrup Carlsen, M. T. Ventura, Igor Kaidashev, Stephen R. Durham, Motohiro Ebisawa, Oliver Pfaar, Hae-Sim Park, Daniel Laune, Wytske Fokkens, Antonella Muraro, Moises A. Calderon, Torsten Zuberbier, Mohamed H. Shamji, Mark S. Dykewicz, Roy Gerth van Wijk, Josep M. Antó, Samantha Walker, Petr Panzner, Giorgio Walter Canonica, Nelson Rosario, Juan Carlos Ivancevich, Holger J. Schünemann, Susanne Halken, Lorenzo Cecchi, Sinthia Bosnic-Anticevich, Violeta Kvedariene, Stefania La Grutta, João Fonseca, Marek L Kowalski, Tari Haahtela, Aziz Sheikh, Montserrat Fernandez-Rivas, Nhan Pham-Thi, Isabelle Bosse, Jean Bousquet, Lan Le, Despo Ierodiakonou, Tomohisa Iinuma, Lars Jacobsen, Christine Rolland, Gert Marien, Wienczyslawa Czarlewski, Glenis Scadding, Ioana Agache, Bolesław Samoliński, Olga Lourenço, Ludger Klimek, Yoshitaka Okamoto, Ulrich Wahn, Joaquim Mullol, Erkka Valovirta, Luigi Caraballo, Sanna Toppila-Salmi, Ioanna Tsiligianni, Derek K. Chu, Ruby Pawankar, Jean Luc Fauquert, Musa Khaitov, Jorg Kleine Tebbe, Jean-François Fontaine, Victoria Cardona, Désirée Larenas-Linemann, Thomas B. Casale, Omer Kalayci, Alvaro A. Cruz, Arunas Valiulis, Anna Bedbrook, Susanne Lau, Alkis Togias, H.-J. Malling, Claus Bachert, Dermot Ryan, Elísio Costa, Giovanni Passalacqua, Ignacio J. Ansotegui, Ana Todo Bom, Marek Jutel, Enrica Menditto, Piotr Kuna, Nikolaos G. Papadopoulos, Gregoire Mercier, Mario Sánchez-Borges, Karl-Christian Bergmann, Susan Waserman, Gunter J. Sturm, Maryline Valentin-Rostan, Arzu Yorgancioglu, Giovanni Battista Pajno, Jan Brozek, George Du Toit, Robyn E O'Hehir, Peter Hellings, Graham Roberts, uBibliorum, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Center for Rhinology and Allergology, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Department of Clinical Epidemiology and Biostatistics and Medicine, McMaster University [Hamilton, Ontario], Department of Allergy and Immunology, Hospital Quiròn Bizkaia Erandio, UPC Research Laboratories, Allergy Department, University of Crete [Heraklion] (UOC), Department of Allergy and Clinical Immunology, Transylvania University of Brasov, Universitat Pompeu Fabra [Barcelona] (UPF), Ghent University Hospital, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Department of Dermatology and Allergy [Berlin, Allemagne], Comprehensive Allergy Center [Berlin, Allemagne], Berlin Institute of Health (BIH)-Berlin Institute of Health (BIH), The University of Sydney, Woolcock Institute of Medical Research [Sydney], CHU Montpellier, Departments of Clinical Epidemiology and Biostatistics and Medicine [Ontario], Section of Allergy and Clinical Immunology [London, UK], Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute, Humanitas Clinical and Research Center [Rozzano, Milan, Italy], Institute for Immunological Research (University of Cartagena), University of Cartagena, Allergy Section, Department of Internal Medicine, Vall d'Hebron University Hospital [Barcelona], Division of Allergy and Immunology, Department of Medicine, Creighton University, Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, ON, Canada, Universidade do Porto, Instituto de Biologia Molecular e Celular (IBMC), Universidade Federal da Bahia (UFBA), UCB Pharma, Colombes, Section of Allergy and Clinical Immunology, Imperial College London-Royal Brompton Hospital-National Heart and Lung Institute [UK], King‘s College London, Saint Louis University School of Medicine [St Louis], Sagamihara National Hospital, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos [Madrid, Spain] (IdISSC), European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Center of Research in Health Technologies and Information Systems (CINTESIS), Department of Allergology, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Helsinki University Hospital, Odense University Hospital, University Hospitals Leuven [Leuven], Chiba University Hospital, Servicio de Alergia e ImmunologiaBuenos Aires (Clinica Santa Isabel), Research Centre for Prevention and Health (RCPH), Department of Public Health [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Capital Region of Denmark, Department of Clinical Immunology, Wroclaw Medical University, Ukrainina Medical Stomatological Academy [Poltava, Ukraine], Laboratory of Molecular Immunology [Moscow, Russian Federation] (National Research Center), Institute of Immunology [Moscow, Russian Federation]-Federal Medicobiological Agency [Moscow, Russian Federation], Hacettepe University = Hacettepe Üniversitesi, Allergy & Asthma Center Westend, Outpatient Clinic Hanf, Department of Immunology, Rheumatology and Allergy, Division of Internal Medicine, Asthma and Allergy, Medical University of Łódź (MUL)-Barlicki University Hospital, Vilnius University [Vilnius], CNR-IBIM : National Research Council-Institute of Biomedicine and Molecular Immunology, Department of Pediatric Pneumology and Immunology, Ho Chi Minh City University of Technology (HCMUT), University of Oslo (UiO), Faculty of Health Sciences and CICS-UB (Health Sciences Research Centre), 'Federico II' University of Naples Medical School, Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Food Allergy Referral Centre Veneto Region [Padua, Italy], Universita degli Studi di Padova, Monash University [Melbourne], Department of Otorhinolaryngology, Department of Pediatrics, Allergy Unit, University of Messina, Ajou University School of Medicine, Department of Allergology and Clinical Immunology, Medical Faculty in Pilsen-Charles University in Prague - the First Faculty of Medicine, Allergy and Respiratory Diseases, University of Genoa (UNIGE), Saint Mary's Hospital [London], St Mary's Hospital [London], Department of Pediatrics, Nippon Medical School, Pediatrics, Universidade Federal do Paraná (UFPR), Medical Centre, Woodbrook Medical Centre, Medical University of Warsaw - Poland, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw - Poland-Faculté de Pharmacie de Paris, Department of Allergy and Clinical Immunology [Caracas, Venezuela], Centro Medico-Docente La Trinidad, The Royal National Throat, Nose and Ear Hospital, Imperial College London, Centre for Population Health Sciences, University of Edinburgh, Medical University Graz, University of Coimbra [Portugal] (UC), Vilnius University Clinic of Children's Diseases, Suomen Terveystalo Allergy Clinic, Università degli studi di Bari Aldo Moro (UNIBA), Department for Pediatric Pneumology and Immunology, Asthma UK Centre in Allergic Mechanisms of Asthma, King's College London, (MRC), Guy's Hospital [London], Nova Southeastern University (NSU), Department of Pulmonology, Manisa Celal Bayar University, Department of Dermatology, Medical School-Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Association Asthme et Allergie, Internal Medicine, Bousquet, J., Pfaar, O., Togias, A., Schunemann, H. J., Ansotegui, I., Papadopoulos, N. G., Tsiligianni, I., Agache, I., Anto, J. M., Bachert, C., Bedbrook, A., Bergmann, K. -C., Bosnic-Anticevich, S., Bosse, I., Brozek, J., Calderon, M. A., Canonica, G. W., Caraballo, L., Cardona, V., Casale, T., Cecchi, L., Chu, D., Costa, E., Cruz, A. A., Czarlewski, W., Durham, S. R., Du Toit, G., Dykewicz, M., Ebisawa, M., Fauquert, J. L., Fernandez-Rivas, M., Fokkens, W. J., Fonseca, J., Fontaine, J. -F., Gerth van Wijk, R., Haahtela, T., Halken, S., Hellings, P. W., Ierodiakonou, D., Iinuma, T., Ivancevich, J. C., Jacobsen, L., Jutel, M., Kaidashev, I., Khaitov, M., Kalayci, O., Kleine Tebbe, J., Klimek, L., Kowalski, M. L., Kuna, P., Kvedariene, V., La Grutta, S., Larenas-Linemann, D., Lau, S., Laune, D., Le, L., Lodrup Carlsen, K., Lourenco, O., Malling, H. -J., Marien, G., Menditto, E., Mercier, G., Mullol, J., Muraro, A., O'Hehir, R., Okamoto, Y., Pajno, G. B., Park, H. -S., Panzner, P., Passalacqua, G., Pham-Thi, N., Roberts, G., Pawankar, R., Rolland, C., Rosario, N., Ryan, D., Samolinski, B., Sanchez-Borges, M., Scadding, G., Shamji, M. H., Sheikh, A., Sturm, G. J., Todo Bom, A., Toppila-Salmi, S., Valentin-Rostan, M., Valiulis, A., Valovirta, E., Ventura, M. -T., Wahn, U., Walker, S., CORBO UGULINO, Wallace, Waserman, S., Yorgancioglu, A., Zuberbier, T., Hospital Quirónsalud Bizkaia [Bilbao], Sagamihara National Hospital [Kanagawa, Japan], Universidade do Porto = University of Porto, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Capital Region of Denmark, Wrocław Medical University, Università degli Studi di Padova = University of Padua (Unipd), Charles University [Prague] (CU)-Medical Faculty in Pilsen, Università degli studi di Genova = University of Genoa (UniGe), Centro Médico Docente La Trinidad, Università degli studi di Bari Aldo Moro = University of Bari Aldo Moro (UNIBA), and Hibade, Monique
Subjects: Cost effectiveness, [SDV]Life Sciences [q-bio], Cost-Benefit Analysis, Comorbidity, medicine.disease_cause, 0302 clinical medicine, Allergen, Cost of Illness, Immunology and Allergy, Medicine, 030212 general & internal medicine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Precision Medicine, mHealth, Children, media_common, Allergen immunotherapy, Rhinitis, Disease Management, 3. Good health, [SDV] Life Sciences [q-bio], rhiniti, Treatment Outcome, Practice Guidelines as Topic, Critical Pathways, [SDV.IMM]Life Sciences [q-bio]/Immunology, Disease Susceptibility, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, medicine.medical_specialty, [SDV.IMM] Life Sciences [q-bio]/Immunology, Attitude of Health Personnel, Immunology, Clinical Decision-Making, 03 medical and health sciences, Pharmacotherapy, rhinitis, stratification, children, media_common.cataloged_instance, Animals, Humans, European union, Intensive care medicine, allergen immunotherapy, asthma, children, mHealth, rhinitis, stratification, Asthma, business.industry, Allergens, asthma, medicine.disease, Rhinitis, Allergic, Review article, 030228 respiratory system, Desensitization, Immunologic, allergen immunotherapy, Stratification, business, Biomarkers
Abstract: Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including health professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as on the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow up of patients. This article is protected by copyright. All rights reserved.
Published: 2019
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11. Mobile technology offers novel insights into the control and treatment of allergic rhinitis: The MASK study

Author: Niels H. Chavannes, Oliver Pfaar, Peter Valentin Tomazic, Antonio Valero, Jean-François Fontaine, Sara Shamai, Gabrielle L. Onorato, Jane da Silva, Ralph Mösges, I. Annesi-Maesano, Piotr Kuna, Violeta Kvedariene, Sanna Toppila-Salmi, Arunas Valiulis, Rute Almeida, Philippe Devillier, Rafael Stelmach, Regina Roller-Wirnsberger, Sietze Reitsma, Tari Haahtela, Ioana Agache, Ruth Murray, Claus Bachert, Gert De Vries, Michael Makris, Esben Eller, Carsten Bindslev-Jensen, Josep M. Antó, João O. Malva, R. Emuzyte, Benoit Pugin, Arzu Yorgancioglu, Ana Todo-Bom, Enrica Menditto, Wienczyslawa Czarlewski, Isabelle Bosse, Ana Margarida Pereira, Mário Morais-Almeida, Cemal Cingi, Emmanuel P. Prokopakis, Ingrid Kull, José Miguel Fuentes-Pérez, Mike Bewick, João Fonseca, Alvaro A. Cruz, Aziz Sheikh, Annabelle Bédard, Mark S. Dykewicz, Xavier Basagaña, Anna Bedbrook, Sinthia Bosnic-Anticevich, Ludger Klimek, Jean Bousquet, Magnus Wickman, Joaquim Mullol, Susan Waserman, Cristiana Stellato, Dermot Ryan, Judith Garcia-Aymerich, Erik Melén, Dana Wallace, Yunuen Rocío Huerta-Villalobos, Thomas B. Casale, Sylvie Arnavielhe, Bilun Gemicioglu, Daniel Laune, Fotis Psarros, Nikos G. Papadopoulos, Bolesław Samoliński, Maria Teresa Ventura, Erkka Valovirta, Robyn E O'Hehir, Peter Hellings, V. Cardona, Michiel van Eerd, Pascal Demoly, Wytske Fokkens, Elísio Costa, Ignacio J. Ansotegui, Désirée Larenas-Linnemann, ISGlobal, Barcelona, Spain, Universitat Pompeu Fabra (UPF), Barcelona, Spain, CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain, UPRES EA220, Pôle des Maladies des Voies Respiratoires, Hôpital Foch, Université Paris-Saclay, Suresnes, France, KYomed INNOV, Montpellier, France, MACVIA-France, Fondation partenariale FMC VIA-LR, Montpellier, France, Medical Consulting Czarlewski, Levallois, France, Medical Communications Consultant, MedScript, Dundalk, and OPC, Cambridge, United Kingdom, Center for Health Technology and Services Research–CINTESIS, Faculdade de Medicina, Universidade do Porto, and Medida, Porto, Portugal, UCIBIO, REQUINTE, Faculty of Pharmacy and Competence Center on Active and Healthy Ageing of University of Porto (Porto4Ageing), Porto, Portugal, Institute of Biomedical Imaging and Life Sciences (IBILI), Faculty of Medicine, University of Coimbra, and the Ageing@Coimbra EIP-AHA Reference Site, Coimbra, Portugal, Allergy Center, CUF Descobertas Hospital, Lisbon, Portugal, Allergy Unit, CUF-Porto Hospital and Institute, and the Center for Research in Health Technologies and information systems CINTESIS, Universidade do Porto, Porto, Portugal, Imunoalergologia, Centro Hospitalar Universitário de Coimbra and Faculty of Medicine, University of Coimbra, Coimbra, Portugal, CIRFF, Federico II University, Naples, Italy, Department of Medicine, Surgery and Dentistry 'Scuola Medica Salernitana', University of Salerno, Salerno, Italy, Unit of Geriatric Immunoallergology, University of Bari Medical School, Bari, Italy, ProAR–Nucleo de Excelencia em Asma, Federal University of Bahia, and the WHO GARD Planning Group, Brazil, Pulmonary Division, Heart Institute (InCor), Hospital da Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, Sao Paulo, Brazil, Department of Internal Medicine and Allergy Clinic of Professor Polydoro Ernani de São Thiago University Hospital, Federal University of Santa Catarina (UFSC), Florianopolis, Brazil, Center of Excellence in Asthma and Allergy, Hospital Médica Sur, México City, Mexico, Hospital General Region 1, Dr Carlos Mc Gregor Sanchez Navarro' IMSS, Mexico City, Mexico, Clinic of Children's Diseases, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, Faculty of Medicine, Vilnius University, Vilnius, Lithuania, Vilnius University Institute of Clinical Medicine, Clinic of Children's Diseases, and the Institute of Health Sciences, Department of Public Health, Vilnius, Lithuania, European Academy of Paediatrics (EAP/UEMS-SP), Brussels, Belgium, Division of Internal Medicine, Asthma and Allergy, Barlicki University Hospital, Medical University of Lodz, Lodz, Poland, Department of Prevention of Environmental Hazards and Allergology, Medical University of Warsaw, Warsaw, Poland, Center for Rhinology and Allergology, Wiesbaden, Department of Otorhinolaryngology, Head and Neck Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, Institute of Medical Statistics, and Computational Biology, Medical Faculty, University of Cologne, and CRI-Clinical Research International, Hamburg, Germany, University Hospital, Montpellier, France, Department of Otorhinolaryngology, Head and Neck Surgery, Section for Rhinology and Allergy, University Hospital Marburg, Phillipps-Universität, Marburg, Germany, Epidemiology of Allergic and Respiratory Diseases, Department Institute Pierre Louis of Epidemiology and Public Health, INSERM and UPMC Sorbonne Université, Medical School Saint Antoine, Paris, France, Allergist, La Rochelle, France, Department of Respiratory Diseases, Montpellier University Hospital, Montpellier, France, Allergist, Reims, France, Allergy Section, Department of Internal Medicine, Hospital Vall'dHebron & ARADyAL Research Network, Barcelona, Spain, Rhinology Unit & Smell Clinic, ENT Department, Hospital Clínic, and Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, CIBERES, University of Barcelona, Barcelona, Spain, Pneumology and Allergy Department CIBERES and Clinical & Experimental Respiratory Immunoallergy, IDIBAPS, University of Barcelona, Barcelona, Spain, Department of Internal Medicine, Medical University of Graz, Graz, Austria, Department of ENT, Medical University of Graz, Graz, Austria, Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, Netherlands, Department of Otorhinolaryngology, Amsterdam University Medical Centres, AMC, Amsterdam, Netherlands, iQ4U Consultants, London, United Kingdom, Allergy and Respiratory Research Group, University of Edinburgh, Edinburgh, United Kingdom, Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, United Kingdom, Skin and Allergy Hospital, Helsinki University Hospital, Helsinki, Finland, Department of Lung Diseases and Clinical Immunology, University of Turku and Terveystalo allergy clinic, Turku, Finland, Allergy Unit 'D Kalogeromitros', 2nd Department of Dermatology and Venereology, National & Kapodistrian University of Athens, 'Attikon' University Hospital, Athens, Greece, Center for Pediatrics and Child Health, Institute of Human Development, Royal Manchester Children's Hospital, University of Manchester, and UK Allergy Department, 2nd Pediatric Clinic, Athens General Children's Hospital 'P&A Kyriakou', University of Athens, Athens, Greece, Department of Otorhinolaryngology University of Crete School of Medicine, Heraklion, Greece, Allergy Department, Athens Naval Hospital, Athens, Greece, Eskisehir Osmangazi University, Medical Faculty, ENT Department, Eskisehir, Turkey, Department of Pulmonary Diseases, Istanbul University-Cerrahpasa, Cerrahpasa Faculty of Medicine, Istanbul, Turkey, Department of Pulmonary Diseases, Celal Bayar University, Faculty of Medicine, Manisa (and the GARD Executive Committee), Manisa, Turkey, Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia, Woolcock Emphysema Centre and Local Health District, Glebe, Australia, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital and Central Clinical School, and the Department of Immunology, Monash University, Melbourne, Australia, Upper Airways Research Laboratory, ENT Department, Ghent University Hospital, Ghent, Belgium, Department of Otorhinolaryngology, University Hospitals Leuven, and the Academic Medical Center, University of Amsterdam, and Euforea, Brussels, Belgium, European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA), Brussels, Belgium, Department of Dermatology and Allergy Centre, Odense University Hospital, Odense Research Center for Anaphylaxis (ORCA), Odense, Denmark, Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, and Sach's Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden, Sachs' Children and Youth Hospital, Södersjukhuset, Stockholm and Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden, Centre for Clinical Research Sörmland, Uppsala University, Eskilstuna, Sweden, Peercode BV, Geldermalsen, Netherlands, Transylvania University Brasov, Brasov, Romania, Department of Allergy and Immunology, Hospital Quirón Bizkaia, Erandio, Spain, Section of Allergy and Immunology, Saint Louis University School of Medicine, Saint Louis, Mo, United States, Division of Allergy/Immunology, University of South Florida, Tampa, Fla, United States, Nova Southeastern University, Fort Lauderdale, Fla, United States, Department of Medicine, Clinical Immunology and Allergy, McMaster University, Hamilton, Ontario, Canada, INSERM U 1168, VIMA: Ageing and chronic diseases Epidemiological and Public Health Approaches, Villejuif, Université Versailles St-Quentin-en-Yvelines, Montigny le Bretonneux, and Euforea, Brussels, Belgium, İÜC, Cerrahpaşa Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, CIBER de Epidemiología y Salud Pública (CIBERESP), Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), Hôpital Foch [Suresnes], Kyomed, Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Nîmes (CHU Nîmes)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-European Innovation Partnership on Active and Healthy Ageing Reference Site (EIP on AHA), Commission Européenne-Commission Européenne-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), MedScript Ltd, Universidade do Porto, Centre for Research in Health Technologies and Information Systems (CINTESIS), Instituto de Biologia Molecular e Celular (IBMC), University of Coimbra [Portugal] (UC), Allergy and Clinical Immunology Department, Hospital CUF-Descobertas, 'Federico II' University of Naples Medical School, Università degli studi di Bari Aldo Moro (UNIBA), Universidade Federal da Bahia (UFBA), Hospital Medica Sur, Vilnius University [Vilnius], Vilnius University Clinic of Children's Diseases, Medical University of Łódź (MUL), Medical University of Warsaw - Poland, Center for Rhinology and Allergology, Institute of Medical Statistics, Informatics and Epidemiology (IMSIE), University of Cologne, Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Mannheim, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Vall d'Hebron University Hospital [Barcelona], Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Medical University Graz, iQ4U consultants Ltd, University of Edinburgh, University of Helsinki, Suomen Terveystalo Allergy Clinic, Eskisehir Osmangazi University, Cerrahpasa Faculty of Medicine, Istanbul University, Department of Pulmonology, Manisa Celal Bayar University, Woolcock Institute of Medical Research [Sydney], The University of Sydney, Department of Allergy, Immunology and Respiratory Medicine, Alfred Hospital-Monash University Building, AMREP, Ghent University Hospital, University Hospitals Leuven [Leuven], Department of Dermatology and Allergy Centre, Odense University Hospital, Institute of Environmental Medicine [Stockholm, Sweden], Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm]-Astrid Lindgren Children's Hospital, Peercode (Développement de l'application) Oudenhof 4c 4191 NW Geldermalsen, Pays-Bas., Department of Allergy and Clinical Immunology, Transylvania University of Brasov, Department of Allergy and Immunology, Hospital Quiròn Bizkaia Erandio, Saint Louis University School of Medicine [St Louis], University of South Florida [Tampa] (USF), Nova Southeastern University (NSU), McMaster University [Hamilton, Ontario], Hôpital Arnaud de Villeneuve [CHRU Montpellier], Department of Dermatology, Allergology and Venereology, HUS Inflammation Center, Ear, Nose and Throat, AII - Inflammatory diseases, Bedard, A., Basagana, X., Anto, J. M., Garcia-Aymerich, J., Devillier, P., Arnavielhe, S., Bedbrook, A., Onorato, G. L., Czarlewski, W., Murray, R., Almeida, R., Fonseca, J., Costa, E., Malva, J., Morais-Almeida, M., Pereira, A. M., Todo-Bom, A., Menditto, E., Stellato, C., Ventura, M. T., Cruz, A. A., Stelmach, R., da Silva, J., Larenas-Linnemann, D., Fuentes-Perez, J. M., Huerta-Villalobos, Y. R., Emuzyte, R., Kvedariene, V., Valiulis, A., Kuna, P., Samolinski, B., Klimek, L., Mosges, R., Pfaar, O., Shamai, S., Annesi-Maesano, I., Bosse, I., Demoly, P., Fontaine, J. -F., Cardona, V., Mullol, J., Valero, A., Roller-Wirnsberger, R. E., Tomazic, P. V., Chavannes, N. H., Fokkens, W. J., Reitsma, S., Bewick, M., Ryan, D., Sheikh, A., Haahtela, T., Toppila-Salmi, S., Valovirta, E., Makris, M., Papadopoulos, N. G., Prokopakis, E. P., Psarros, F., Cingi, C., Gemicioglu, B., Yorgancioglu, A., Bosnic-Anticevich, S., O'Hehir, R. E., Bachert, C., Hellings, P. W., Pugin, B., Bindslev-Jensen, C., Eller, E., Kull, I., Melen, E., Wickman, M., De Vries, G., van Eerd, M., Agache, I., Ansotegui, I. J., Dykewicz, M. S., Casale, T., Wallace, D., Waserman, S., Laune, D., and Bousquet, J.
Subjects: Male, Allergy, Lydia Becker Institute, Visual Analog Scale, IMPACT, Efficiency, THERAPY, Allergic rhinitis, law.invention, corticosteroids, FLUTICASONE, 0302 clinical medicine, Randomized controlled trial, law, Adrenal Cortex Hormones, conjunctiviti, conjunctivitis, Immunology and Allergy, AZELASTINE, 030212 general & internal medicine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Child, Aged, 80 and over, treatment, Middle Aged, WORK PRODUCTIVITY, Mobile Applications, 3. Good health, Child, Preschool, GUIDED SELF-MANAGEMENT, Histamine H1 Antagonists, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Symptom Assessment, medicine.drug, Adult, corticosteroid, medicine.medical_specialty, antihistamines, MASK, Adolescent, Visual analogue scale, Immunology, Mometasone furoate, antihistamine, Fluticasone propionate, 03 medical and health sciences, Young Adult, ResearchInstitutes_Networks_Beacons/lydia_becker_institute_of_immunology_and_inflammation, asthma, mobile health, Allergic rhiniti, medicine, QUALITY, Humans, Asthma, Aged, business.industry, Infant, Newborn, Infant, medicine.disease, Azelastine, Rhinitis, Allergic, 030228 respiratory system, 3121 General medicine, internal medicine and other clinical medicine, Physical therapy, Observational study, business, TRADITIONAL TREATMENT
Abstract: Demoly, Pascal/0000-0001-7827-7964; Chavannes, Niels/0000-0002-8607-9199; Basagana, Xavier/0000-0002-8457-1489; N.G., Papadopoulos/0000-0002-4448-3468; Almeida, Rute/0000-0001-7755-5002; Pereira, Ana Margarida/0000-0002-5468-0932; Gemicioglu, Bilun/0000-0001-5953-4881; Bedard, Annabelle/0000-0002-7842-8889; Anto, J M/0000-0002-4736-8529; Fonseca, Joao Almeida/0000-0002-0887-8796; Rodo, Xavier/0000-0003-4843-6180; stelmach, rafael/0000-0002-5132-1934; J, Garcia-Aymerich/0000-0002-7097-4586; orlando, valentina/0000-0002-8209-8878; Cardona, Victoria/0000-0003-2197-9767; yorgancioglu, arzu/0000-0002-4032-0944; Bindslev-Jensen, Carsten/0000-0002-8940-038X; VENTURA, Maria Teresa/0000-0002-2637-4583; O'Hehir, Robyn/0000-0002-3489-7595; Costa, Elisio/0000-0003-1158-1480; Malva, Joao/0000-0002-5438-4447; Pugin, Benoit/0000-0001-7132-9477; Psarros, Fotis/0000-0002-2928-150X; Kuna, Piotr/0000-0003-2401-0070 WOS:000473432800017 PubMed ID: 30951790 Background: Mobile health can be used to generate innovative insights into optimizing treatment to improve allergic rhinitis (AR) control. Objectives: A cross-sectional real-world observational study was undertaken in 22 countries to complement a pilot study and provide novel information on medication use, disease control, and work productivity in the everyday life of patients with AR. Methods: A mobile phone app (Allergy Diary, which is freely available on Google Play and Apple stores) was used to collect the data of daily visual analogue scale (VAS) scores for (1) overall allergic symptoms; (2) nasal, ocular, and asthma symptoms; (3) work; and (4) medication use by using a treatment scroll list including all allergy medications (prescribed and over-the-counter) customized for 22 countries. The 4 most common intranasal medications containing intranasal corticosteroids and 8 oral H-1-antihistamines were studied. Results: Nine thousand one hundred twenty-two users filled in 112,054 days of VASs in 2016 and 2017. Assessment of days was informative. Control of days with rhinitis differed between no (best control), single (good control for intranasal corticosteroid-treated days), or multiple (worst control) treatments. Users with the worst control increased the range of treatments being used. The same trend was found for asthma, eye symptoms, and work productivity. Differences between oral H-1-antihistamines were found. Conclusions: This study confirms the usefulness of the Allergy Diary in accessing and assessing behavior in patients with AR. This observational study using a very simple assessment tool (VAS) on a mobile phone had the potential to answer questions previously thought infeasible. Sanofi AventisSanofi-Aventis; GlaxoSmithKlineGlaxoSmithKline; North Portugal Regional Operational Programme; European Regional Development Fund (ERDF)European Union (EU); Mundipharm; Teva Pharma; AstraZenecaAstraZeneca; Boehringer IngelheimBoehringer Ingelheim; Chiesi; MEDA Pharma; Sao Paulo Research FoundationFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP); NovartisNovartis; Chiesi, DBV Technologies; UCBUCB Pharma SA; SanofiSanofi-Aventis; Adamed; FAES, Berlin Chemie; ALK-Abello; Allergopharma, Allergy Therapeutics; ServierServier; ASIT biotech; Hulka; Leti and Stallergenes; Roxall, Atmos, Bionorica; ALK-Abello, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics; Biomay, Nuvo, Circassia; Novartis Pharma; Mundipharma; RocheRoche Holding; Erkko Foundation; Hal Allergy B. V.; Teva; Meda, Stallergenes; Cipla; Mundipharma, Mylan; Sanofi-AventisSanofi-Aventis P. Devillier reports personal fees from Sanofi Aventis, GlaxoSmithKline, AstraZeneca, Chiesi, Meda Pharma, and Menarini outside the submitted work. R. Almeida reports grants from Project NORTE-01-0145-FEDER-000016 (NanoSTIMA) by the North Portugal Regional Operational Programme (NORTE 2020) under the Portugal 2020 Partnership Agreement and through the European Regional Development Fund (ERDF) during the conduct of the study. A. Todo-Bom reports grants and personal fees from GlaxoSmithKline, Mundipharm, and Novartis; personal fees from Teva Pharma and AstraZeneca; and grants from Leti and Bial outside the submitted work. A. A. Cruz reports grants and personal fees from AstraZeneca; grants from GlaxoSmithKline; personal fees from Boehringer Ingelheim, Chiesi, Novartis, Eurofarma, MEDA Pharma, and Boston Scientific outside the submitted work. R. Stelmach reports grants from the Sao Paulo Research Foundation and MSD; grants and personal fees from Novartis, grants, personal fees, and nonfinancial support from AstraZeneca and Chiesi; and personal fees and nonfinancial support from Boehringer Ingelheim outside the submitted work. D. Larenas-Linnemann reports personal fees from Armstrong, AstraZeneca, Boehringer Ingelheim, Chiesi, DBV Technologies, Grunenthal, GlaxoSmithKline, MEDA, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, and UCB and grants from Sanofi, AstraZeneca, Novartis, UCB, GlaxoSmithKline, TEVA, Boehringer Ingelheim, and Chiesi outside the submitted work. V. Kvedariene has received payment for consultancy from GlaxoSmithKline and for lectures from StallergensGreer and Berlin-Chemie outside the submitted work. P. Kuna reports personal fees from Adamed, Boehringer Ingelheim, AstraZeneca, Chiesi, FAES, Berlin Chemie, Novartis, Polpharma, and Allergopharma outside the submitted work. R. Mosges reports personal fees from ALK-Abello, Allergopharma, Allergy Therapeutics, Hexal, Servier, Klosterfrau, Stada, UCB, and Friulchem; grants from ASIT biotech, Nuvo, Bayer, FAES, GlaxoSmithKline, MSD, Johnson & Johnson, Meda, Optima, Ursapharm, BitopAG, and Hulka; grants and personal fees from Bencard; grants from Leti and Stallergenes; grants, personal fees and nonfinancial support from Lofarma; nonfinancial support from Roxall, Atmos, Bionorica, Otonomy, and Ferrero; and personal fees and nonfinancial support from Novartis outside the submitted work. O. Pfaar reports grants and personal fees from ALK-Abello, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, and Lofarma; grants from Biomay, Nuvo, Circassia, and GlaxoSmithKline; and personal fees from Novartis Pharma, MEDA Pharma, Indoor Biotechnologies, and Pohl-Boskamp outside the submitted work. T. Haahtela reports personal fees from Mundipharma, Novartis, and Orion Pharma outside the submitted work. S. Toppila-Salmi reports other support from Biomedical Systems and Roche and grants from the Erkko Foundation outside the submitted work. N. G. Papadopoulos reports grants from Gerolymatos and personal fees from Hal Allergy B. V., Novartis Pharma AG, Menarini, Hal Allergy B. V., and Mylan outside the submitted work. S. Bosnic-Anticevich reports personal fees from Teva, Boehringer Ingelheim, Sanofi, GlaxoSmithKline, and AstraZeneca outside the submitted work. C. Bachert reports personal fees from Meda, Stallergenes, and ALK-Abello (speaker). I. J. Ansotegui reports personal fees from Hikma, Roxall, AstraZeneca, Menarini, UCB, Faes Farma, Sanofi, and Mundipharma outside the submitted work. D.; Wallace reports other from Mylan Pharmaceutical Company outside the submitted work being co-chair of the AAAAI/ACAAI Joint Task Force on Practice Parameters. J. Bousquet reports personal fees and other support from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Sanofi-Aventis, Takeda, Teva, and Uriach outside the submitted work and other support from Kyomed. The rest of the authors declare that they have no relevant conflicts of interest.
Published: 2018
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12. Data publication with the structural biology data grid supports live analysis

Author: Emil F. Pai, Qing R. Fan, Yousif Shamoo, Kevin D. Corbett, Dominika Borek, Tom Kirchhausen, James S. Fraser, Elizabeth Ransey, Stephanie M. Socias, Peter A. Meyer, Enrico Di Cera, Oleg V. Tsodikov, Jason S. McLellan, C. S. Raman, James Withrow, Mercè Crosas, Karen S. Anderson, Carlo Petosa, Filipe R. N. C. Maia, Gabrielle Rudenko, Yorgo Modis, Peng Gong, Walter J. Chazin, Zongchao Jia, Zbyszek Otwinowski, Adrian R. Ferré-D'Amaré, Yunsun Nam, Stephen C. Harrison, Sirano Dhe-Paganon, Joseph Schlessinger, Catherine L. Drennan, Kenneth D. Westover, Holger Sondermann, Richard H. G. Baxter, Marc Kvansakul, Ekaterina E. Heldwein, J. Christopher Fromme, Sean Crosson, Michael K. Rosen, Antonina Roll-Mecak, Robert J. Keenan, Tamir Gonen, Andrew C. Kruse, Ian Foster, Kanagalaghatta R. Rajashankar, Titus J. Boggon, Ming Lei, K. Christopher Garcia, Alexandre M. J. J. Bonvin, Michael S. Cosgrove, Amedeo Caflisch, Michael J. Eck, Brandt F. Eichman, Thomas U. Schwartz, Chung-I Chang, Rachelle Gaudet, Yizhi Jane Tao, Emily C. Tjon, Pedro Pereira, Jason Key, David B. Neau, Stephen C. Blacklow, Kay Diederichs, Hao Wu, Tom A. Rapoport, Alejandro Buschiazzo, Tom J. Brett, Piotr Sliz, Chris Botka, Niraj H. Tolia, Department of Biological Chemistry and Molecular Pharmacology [Boston] (DBCMP), Harvard Medical School [Boston] (HMS), Laboratory of molecular and structural microbiology, Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Shanghai Institutes for Biological Sciences (Institute of Biochemistry and Cell Biology), Chinese Academy of Sciences [Beijing] (CAS), NE-CAT and department of chemistry and chemical biology [Argonne], Cornell University, Departments of pharmacology and molecular biophysics and biochemistry [New Haven], Yale University School of Medicine, Department of Chemistry and Molecular Biophysics & Biochemistry [New Haven], Yale University [New Haven], Bijovet center [Utrecht], Utrecht University [Utrecht], Department of Biophysics and Biochemistry [Dallas], University of Texas Southwestern Medical Center [Dallas], Department of Internal Medicine [St Louis], Washington University School of Medicine, Department of Biochemistry [Zurich], University of Zürich [Zürich] (UZH), Institute of Biological Chemistry (IBC Sinica), Academia Sinica, Departments of biochemistry and chemistry [Nashville], Vanderbilt University [Nashville], Ludwig Institute for Cancer Research, University of California [San Diego] (UC San Diego), University of California, SUNY Upstate Medical University, State University of New York (SUNY), University of Chicago, Dana-Farber Cancer Institute [Boston], Saint Louis University School of Medicine [St Louis], Massachusetts Institute of Technology (MIT), Department of Biological Chemistry and Molecular Pharmacology (DBCMP), Columbia University [New York], National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Weill Institute for Cell and Molecular Biology, Howard Hughes Medical Institute [Stanford], Stanford University School of Medicine [CA, USA], Harvard University [Cambridge], Wuhan Institute of Virology, Howard Hughes Medical Institute [Boston], Tufts University School of Medicine [Boston], Queen's University [Kingston], La Trobe University [Melbourne], Geisel School of Medicine at Dartmouth, University of Cambridge [UK] (CAM), University of Texas at Dallas [Richardson] (UT Dallas), Campbell Family Institute for Breast Cancer Research, University Health Network, University of Toronto, Instituto de Biologia Molecular e Celular (IBMC), Institut de biologie structurale (IBS - UMR 5075), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), University of Maryland [Baltimore County] (UMBC), University of Maryland System, National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH), Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch (UTMB), Rice University [Houston], University of Washington School of Medicine, University of Kentucky, Boston Children's Hospital, Department of Computer Science, University of Chicago, University of California [San Francisco] (UCSF), Uppsala University, Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Howard Hughes Medical Institute [Ashburn], Fachbereich Biologie, University of Konstanz, Institute for Quantitative Social Sciences, Development of the Structural Biology Data Grid is funded by The Leona M. and Harry B. Helmsley Charitable Trust 2016PG-BRI002 to PS and MC. Development of citation workflows is supported NSF 1448069 (to PS). DAA is being developed as a pilot project of the National Data Service, with additional funds to support storage and technology development, including NIH P41 GM103403 (NE-CAT) and 1S10RR028832 (HMS) and DOE DE-AC02-06CH11357, NIH 1U54EB020406-01, Big Data for Discovery Science Center, and NIST 60NANB15D077 (Globus Project), Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemistry, Drennan, Catherine L., Schwartz, Thomas, Sub NMR Spectroscopy, NMR Spectroscopy, Instituto de Investigação e Inovação em Saúde, Molecular and structural microbiology / Microbiología Molecular y Estructural [Montevideo], Cornell University [New York], Universität Zürich [Zürich] = University of Zurich (UZH), Howard Hughes Medical Institute (HHMI), Queen's University [Kingston, Canada], Institut de biologie structurale (IBS - UMR 5075 ), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), University of Zurich, Sliz, Piotr, Yale School of Medicine [New Haven, Connecticut] (YSM), University of California (UC), Harvard University, Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), University of Kentucky (UK), University of California [San Francisco] (UC San Francisco), Harrison, Seamus Conor [0000-0003-1480-1143], Modis, Yorgo [0000-0002-6084-0429], and Apollo - University of Cambridge Repository
Subjects: 0301 basic medicine, Chemistry(all), Experiences, General Physics and Astronomy, computer.software_genre, Crystallography, X-Ray, Biochemistry, Software, Structural Biology, Databases, Genetic, Structure models, Macromolecular crystallography, media_common, Strukturbiologi, Uncategorized, Multidisciplinary, Crystallography, Data grid, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Publications, X-ray scattering, 1.5 Resources and infrastructure (underpinning), 3100 General Physics and Astronomy, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Networking and Information Technology R&D, Networking and Information Technology R&D (NITRD), The Internet, Data mining, Macromolecular Substances, media_common.quotation_subject, Science, 610 Medicine & health, 1600 General Chemistry, Biology, Physics and Astronomy(all), General Biochemistry, Genetics and Molecular Biology, Article, Synchrotron, 03 medical and health sciences, Databases, Genetic, Underpinning research, 1300 General Biochemistry, Genetics and Molecular Biology, ddc:570, 10019 Department of Biochemistry, Quality (business), Internet, business.industry, Biochemistry, Genetics and Molecular Biology(all), Data quality, Experimental data, General Chemistry, Data science, 030104 developmental biology, Data access, Protein data-bank, Paradigm shift, X-Ray, 570 Life sciences, biology, Resolution, business, computer, Department of Biochemistry, Genetics and Molecular Biology(all)
Abstract: Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data.sbgrid.org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis., The validation and analysis of X-ray crystallographic data is essential for reproducibility and the development of crystallographic methods. Here, the authors describe a repository for crystallographic datasets and demonstrate some of the ways it could serve the crystallographic community.
Published: 2016
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13. Data publication with the structural biology data grid supports live analysis

Author: Pa, Meyer, Socias S, Key J, Ransey E, Ec, Tjon, Alejandro Buschiazzo, Lei M, Botka C, Withrow J, Neau D, Rajashankar K, Ks, Anderson, Rh, Baxter, Sc, Blacklow, Tj, Boggon, Am, Bonvin, Borek D, Tj, Brett, Caflisch A, Ci, Chang, Department of Biological Chemistry and Molecular Pharmacology [Boston] (DBCMP), Harvard Medical School [Boston] (HMS), Molecular and structural microbiology = Microbiología Molecular y Estructural [Montevideo], Institut Pasteur de Montevideo, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Shanghai Institutes for Biological Sciences (Institute of Biochemistry and Cell Biology), Chinese Academy of Sciences [Beijing] (CAS), NE-CAT and department of chemistry and chemical biology [Argonne], Cornell University, Departments of pharmacology and molecular biophysics and biochemistry [New Haven], Yale University School of Medicine, Department of Chemistry and Molecular Biophysics & Biochemistry [New Haven], Yale University [New Haven], Bijovet center [Utrecht], Utrecht University [Utrecht], Department of Biophysics and Biochemistry [Dallas], University of Texas Southwestern Medical Center [Dallas], Department of Internal Medicine [St Louis], Washington University School of Medicine, Department of Biochemistry [Zurich], University of Zürich [Zürich] (UZH), Institute of Biological Chemistry (IBC Sinica), Academia Sinica, Departments of biochemistry and chemistry [Nashville], Vanderbilt University [Nashville], Ludwig Institute for Cancer Research, University of California [San Diego] (UC San Diego), University of California, SUNY Upstate Medical University, State University of New York (SUNY), University of Chicago, Dana-Farber Cancer Institute [Boston], Saint Louis University School of Medicine [St Louis], Massachusetts Institute of Technology (MIT), Department of Biological Chemistry and Molecular Pharmacology (DBCMP), Columbia University [New York], National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), Weill Institute for Cell and Molecular Biology, Howard Hughes Medical Institute [Stanford], Stanford University School of Medicine [CA, USA], Harvard University [Cambridge], Wuhan Institute of Virology, Howard Hughes Medical Institute [Boston], Tufts University School of Medicine [Boston], Queen's University [Kingston], La Trobe University [Melbourne], Geisel School of Medicine at Dartmouth, University of Cambridge [UK] (CAM), University of Texas at Dallas [Richardson] (UT Dallas), Campbell Family Institute for Breast Cancer Research, University Health Network, University of Toronto, Instituto de Biologia Molecular e Celular (IBMC), Institut de biologie structurale (IBS - UMR 5075), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), University of Maryland [Baltimore County] (UMBC), University of Maryland System, National Institute of Neurological Disorders and Stroke [Bethesda] (NINDS), National Institutes of Health [Bethesda] (NIH), Sealy Center for Structural Biology and Molecular Biophysics, The University of Texas Medical Branch (UTMB), Rice University [Houston], University of Washington School of Medicine, University of Kentucky, Boston Children's Hospital, Department of Computer Science, University of Chicago, University of California [San Francisco] (UCSF), Uppsala University, Lawrence Berkeley National Laboratory [Berkeley] (LBNL), Howard Hughes Medical Institute [Ashburn], Fachbereich Biologie, University of Konstanz, Institute for Quantitative Social Sciences, Development of the Structural Biology Data Grid is funded by The Leona M. and Harry B. Helmsley Charitable Trust 2016PG-BRI002 to PS and MC. Development of citation workflows is supported NSF 1448069 (to PS). DAA is being developed as a pilot project of the National Data Service, with additional funds to support storage and technology development, including NIH P41 GM103403 (NE-CAT) and 1S10RR028832 (HMS) and DOE DE-AC02-06CH11357, NIH 1U54EB020406-01, Big Data for Discovery Science Center, and NIST 60NANB15D077 (Globus Project), Department of Biological Chemistry and Molecular Pharmacology [Boston] ( DBCMP ), Harvard Medical School [Boston] ( HMS ), Laboratory of molecular and structural microbiology, Institut Pasteur Montevideo-Réseau International des Instituts Pasteur ( RIIP ), Shanghai Institutes for Biological Sciences ( Institute of Biochemistry and Cell Biology ), Chinese Academy of Sciences [Beijing] ( CAS ), Yale University, Faculty of Science, Utrecht University, University of Zürich [Zürich] ( UZH ), Institute of Biological Chemistry ( IBC Sinica ), Vanderbilt University of Nashville, University of California [San Diego] ( UC San Diego ), Massachusetts Institute of Technology ( MIT ), Department of Biological Chemistry and Molecular Pharmacology ( DBCMP ), National Heart, Lung, and Blood Institute [Bethesda] ( NHLBI ), Stanford University School of Medicine, Havard Medical School, University of Cambridge [UK] ( CAM ), University of Texas at Dallas [Richardson] ( UT Dallas ), Instituto de Biologia Molecular e Celular ( IBMC ), Institut de biologie structurale ( IBS - UMR 5075 ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), University of Maryland Baltimore County [Baltimore] ( UMBC ), National Institute of Neurological Disorders and Stroke [Bethesda] ( NINDS ), National Institutes of Health [Bethesda] ( NIH ), The University of Texas Medical Branch ( UTMB ), Yale School of Medicine, University of California [San Francisco] ( UCSF ), Lawrence Berkeley National Laboratory [Berkeley] ( LBNL ), Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Department of Chemistry, Drennan, Catherine L., Schwartz, Thomas, Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), and Instituto de Investigação e Inovação em Saúde
Subjects: Data set, Data quality, General Physics and Astronomy, Experimental data, General Chemistry, Data grid, General Biochemistry, Genetics and Molecular Biology, Data science, Genetics, Paradigm shift, Data access, Data mining, Biology, The Internet
Abstract: The validation and analysis of X-ray crystallographic data is essential for reproducibility and the development of crystallographic methods. Here, the authors describe a repository for crystallographic datasets and demonstrate some of the ways it could serve the crystallographic community., Access to experimental X-ray diffraction image data is fundamental for validation and reproduction of macromolecular models and indispensable for development of structural biology processing methods. Here, we established a diffraction data publication and dissemination system, Structural Biology Data Grid (SBDG; data.sbgrid.org), to preserve primary experimental data sets that support scientific publications. Data sets are accessible to researchers through a community driven data grid, which facilitates global data access. Our analysis of a pilot collection of crystallographic data sets demonstrates that the information archived by SBDG is sufficient to reprocess data to statistics that meet or exceed the quality of the original published structures. SBDG has extended its services to the entire community and is used to develop support for other types of biomedical data sets. It is anticipated that access to the experimental data sets will enhance the paradigm shift in the community towards a much more dynamic body of continuously improving data analysis.
Published: 2016
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14. Safety and efficacy of boceprevir/peginterferon/ribavirin for HCV G1 compensated cirrhotics: Meta-analysis of 5 trials

Author: Steven L. Flamm, Frans A. Helmond, Savino Bruno, Rafael Esteban, Stefan Zeuzem, Janice Wahl, Lisa D. Pedicone, W. Deng, Michael P. Manns, Jean-Pierre Bronowicki, Fred Poordad, John M. Vierling, Kenneth Koury, Bruce R. Bacon, Paul Y. Kwo, Frank J. Dutko, Mark J. DiNubile, Baylor College of Medicine (BCM), Baylor University, J.W.Goethe University Hospital, Texas Liver Institute [San Antonio], University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth)- The University of Texas Health Science Center at Houston (UTHealth), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Dept. of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School [Hannover] (MHH), Saint Louis University School of Medicine [St Louis], Hospital General, Vall d'Hebron University Hospital [Barcelona], Feinberg School of Medicine, Northwestern University [Evanston], Indiana University School of Medicine, Indiana University System-Indiana University System, Merck Sharp & Dohme Corp. (MSD), Whitehouse Station, and Azienda Ospedaliera Fatebenefratelli e Oftalmico
Subjects: Adult, Liver Cirrhosis, Male, medicine.medical_specialty, Cirrhosis, Proline, Anemia, [SDV]Life Sciences [q-bio], Gastroenterology, Antiviral Agents, Polyethylene Glycols, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Boceprevir, Internal medicine, Ribavirin, medicine, Humans, Adverse effect, Aged, Retrospective Studies, Hepatology, business.industry, Chronic HCV, Interferon-alpha, virus diseases, Hepatitis C, Hepatitis C, Chronic, Middle Aged, medicine.disease, Confidence interval, Recombinant Proteins, digestive system diseases, 3. Good health, Surgery, Clinical trial, Logistic Models, chemistry, Clinical Trials, Phase III as Topic, 030220 oncology & carcinogenesis, RNA, Viral, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, business
Abstract: International audience; BACKGROUND & AIMS:HCV-infected cirrhotics may urgently need therapy but are often under-represented in clinical trials resulting in limited data to guide their management. We performed a meta-analysis of well-compensated cirrhotic patients from five Phase 3 trials.METHODS:Patients received P/R (peginterferon/ribavirin; 4 weeks) followed by BOC (boceprevir)/P/R or P/R for 24, 32, or 44 weeks. Sustained virologic response (SVR) rates were calculated by Metavir score. Multivariate logistic regression (MLR) models identified baseline and on-treatment predictors of SVR. Safety was evaluated by adverse-event (AE) reporting and laboratory monitoring.RESULTS:Pooled meta-estimates for SVR rates (95% confidence interval) in 212 F4 (cirrhotic) patients were 55% (43, 66) with BOC/P/R vs.17% (0, 41) with P/R. MLR identified 4 predictors of SVR in F3/F4 patients: undetectable HCV-RNA at treatment week (TW) 8; ⩾ 1 log10 decline in HCV-RNA from baseline at TW4; male; and baseline HCV-RNA ⩽ 800,000 IU/ml. SVR rate was 89% (65/73) in F4 patients who were HCV-RNA undetectable at TW8. No F3 (0/5) or F4 (0/17) patients with
Published: 2014
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15. Overall safety profile of boceprevir plus peginterferon alfa-2b and ribavirin in patients with chronic hepatitis C genotype 1: a combined analysis of 3 phase 2/3 clinical trials

Author: Paul Y. Kwo, Michael P. Manns, Marc Bourlière, Margaret Burroughs, Lisa D. Pedicone, John M. Vierling, Janice K. Albrecht, Fred Poordad, Luis A. Balart, Heather L. Sings, Mitchel L. Shiffman, Frans A. Helmond, Lorenzo Rossaro, Franco Felizarta, Eugene R. Schiff, M. Davis, Jonathan McCone, Clifford A. Brass, Mark S. Sulkowski, Bruce R. Bacon, Savino Bruno, K. Rajender Reddy, Jean-Pierre Bronowicki, Dept. of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School [Hannover] (MHH), Mount Vernon Endoscopy Center, South Florida Center of Gastroenterology, University of California [Davis] (UC Davis), University of California, Miami University [Ohio] (MU), The Liver Institute of Virginia, Bon Secours Health System, Saint Louis University School of Medicine [St Louis], Service d'hépato-gastro-entérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Johns Hopkins University School of Medicine [Baltimore], Azienda Ospedaliera Fatebenefratelli e Oftalmico, Tulane University Health Sciences Center, Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Indiana University School of Medicine, Indiana University System-Indiana University System, Texas Liver Institute [San Antonio], University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth)- The University of Texas Health Science Center at Houston (UTHealth), Private Practice, Private practice, Pennsylvania State University (Penn State), Penn State System, Merck Sharp & Dohme Corp. (MSD), Whitehouse Station, Baylor College of Medicine (BCM), and Baylor University
Subjects: Adult, Male, medicine.medical_specialty, Combination therapy, Adolescent, Proline, [SDV]Life Sciences [q-bio], Phases of clinical research, Hepacivirus, Neutropenia, Interferon alpha-2, Gastroenterology, Antiviral Agents, Polyethylene Glycols, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, 0302 clinical medicine, Boceprevir, Internal medicine, Ribavirin, antiviral therapy, Medicine, Humans, 030212 general & internal medicine, Adverse effect, Aged, Hepatology, business.industry, Interferon-alpha, Hepatitis C, Chronic, Middle Aged, Victrelis, medicine.disease, Recombinant Proteins, 3. Good health, Surgery, Dysgeusia, chemistry, Peginterferon alfa-2b, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, medicine.symptom, business, medicine.drug
Abstract: Background & Aims Triple therapy with peginterferon/ribavirin (PR) plus an NS3 protease inhibitor has emerged as the standard-of-care for patients with chronic hepatitis C genotype-1. We provide a detailed safety analysis comparing PR to boceprevir plus PR (BOC/PR) across three phase 2/3 studies. Methods SPRINT-1 was an open-label phase 2 study in 595 treatment-naive patients. In the two phase 3 studies, 1500 patients (1097 treatment-naive, SPRINT-2; 403 treatment-failure, RESPOND-2) were randomized to receive PR alone, or one of two regimens where BOC was added to PR after a 4-wk PR lead-in. In this analysis, the respective BOC/PR and PR arms were combined for all three trials. The benefit of shortened duration of treatment using response-guided therapy (RGT) was also explored in the SPRINT-2 trial. Results Only two adverse events, anaemia and dysgeusia, occurred 20% more often with the BOC-containing regimens compared with PR. Nausea, diarrhoea and neutropenia were the only other common events with an incidence of at least 5% greater when BOC was added to the PR backbone. The proportions of patients reporting serious adverse events (AE), life-threatening AEs, and study drug discontinuation because of an AE were similar in the PR and BOC/PR arms. In treatment-naive patients, RGT generally did not result in a lower frequency of common AEs; however, RGT led to decreased exposure to all 3 study drugs and to a decrease in the mean duration of several clinically relevant AEs such as anaemia, neutropenia, fatigue and depression, as well as earlier normalization of haemoglobin and neutrophil counts. Conclusions The safety profile of BOC combination therapy largely reflects the known profile of peginterferon and ribavirin, with incremental haematolgical effects and dysgeusia. Shorter treatment duration with RGT significantly reduced the duration of AEs.
Published: 2014
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16. Effects of Ribavirin Dose Reduction vs Erythropoietin for Boceprevir-Related Anemia in Patients With Chronic Hepatitis C Virus Genotype 1 Infection—A Randomized Trial

Author: Poordad, Fred, Lawitz, Eric, Reddy, K. Rajender, Afdhal, Nezam, Hézode, Christophe, Zeuzem, Stefan, Lee, Samuel, Calleja, Jose Luis, Brown, Robert, Craxi, Antonio, Wedemeyer, Heiner, Nyberg, L. M., Nelson, David, Rossaro, Lorenzo, Balart, Luis, Morgan, Timothy, Bacon, Bruce, Flamm, Steven, Kowdley, Kris, Deng, Weiping, Koury, Kenneth, Pedicone, Lisa, Dutko, Frank, Burroughs, Margaret, Alves, Katia, Wahl, Janice, Brass, Clifford, Albrecht, Janice, Sulkowski, Mark, Bailey, R., Cooper, C., Feinman, S.V., Marotta, P., Tam, E., Wong, F., Bourlière, Marc, Bronowicki, Jean-Pierre, Hezode, Christophe, Tran, A., Goeser, Tobias, Klass, D., Schmid, R., Pirisi, M., Zuin, M., Bennett, M., Bernstein, D., Box, T., Boyer, T., Clain, D., Crippin, J., Davis, M., Felizarta, Franco, Freilich, Bradley, Galati, Joseph, Galler, G., Ghalib, Reem, Gibas, A., Godofsky, E., Gordon, F., Gordon, S., Gross, J., Harrison, S., Herrera, J., Herrine, S., Herring, R., Jacobson, I., Joshi, S., Kilby, A., King, J., Koch, A., Kowdley, Kris V, Kwo, P., Lebovics, E., Lee, W., Levin, J., Li, Xiaojian, Luketic, Velimir, Mailliard, M., Mccone, Jonathan, Mikolich, D., Muir, A., Mullen, K., Nunes, F., Nyberg, A., Pandya, P., Pauly, M., Peine, C., Poleynard, Gary, Poulos, J., Pound, D., Rabinovitz, M., Ravendhran, Natarajan, Reddy, R., Reindollar, Robert, Reuben, A., Riley, T., Rubin, R., Russo, M., Ryan, M., Saab, S., Santoro, J., Schmidt, W., Sepe, T., Sherman, K., Sjögren, Marketa, Slim, J., Smith, C., Stein, L., Strauss, R., Vargas, H., Vierling, John, Witt, D., Wu, G., Younes, Z., Texas Liver Institute [San Antonio], University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth)- The University of Texas Health Science Center at Houston (UTHealth), Division of Gastroenterology (University of Pennsylvania), University of Pennsylvania [Philadelphia], Beth Israel Deaconess Medical Center, Harvard Medical School, Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Johann Wolfgang Goethe University Medical Center, University of Calgary, University Hospital Puerta de Hierro, Madrid, New York Presbyterian Hospital, Università degli studi di Palermo - University of Palermo, Department of Gastroenterology, Hepatology and Endocrinology (MHH), Hannover Medical School [Hannover] (MHH), Kaiser Permanente, University of Florida [Gainesville] (UF), University of California [Davis] (UC Davis), University of California (UC), Tulane University Health Sciences Center, Veterans Affairs Long Beach Healthcare System (VA Long Beach Healthcare System), Saint Louis University School of Medicine [St Louis], Feinberg School of Medicine, Northwestern University [Evanston], Virginia Mason Medical Center, Merck & Co. Inc, Johns Hopkins University School of Medicine [Baltimore], Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), and University of California
Subjects: Male, viruses, [SDV]Life Sciences [q-bio], Hepacivirus, medicine.disease_cause, Gastroenterology, Polyethylene Glycols, law.invention, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Erythropoiesis, Incidence, Disease Management, virus diseases, Anemia, Middle Aged, Recombinant Proteins, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Drug Therapy, Combination, Female, 030211 gastroenterology & hepatology, Algorithms, medicine.drug, medicine.medical_specialty, Genotype, Proline, Side effect, Hepatitis C virus, Interferon alpha-2, Antiviral Agents, 03 medical and health sciences, Internal medicine, Boceprevir, Ribavirin, medicine, Humans, Erythropoietin, DAA, Dose-Response Relationship, Drug, Hepatology, business.industry, Interferon-alpha, Hepatitis C, Chronic, biochemical phenomena, metabolism, and nutrition, medicine.disease, digestive system diseases, Side Effect, Logistic Models, chemistry, Immunology, Hemoglobin, business, EPO
Abstract: International audience; Background & AimsTreatment of hepatitis C virus (HCV) infection with boceprevir, peginterferon, and ribavirin can lead to anemia, which has been managed by reducing ribavirin dose and/or erythropoietin therapy. We assessed the effects of these anemia management strategies on rates of sustained virologic response (SVR) and safety.MethodsPatients (n = 687) received 4 weeks of peginterferon and ribavirin followed by 24 or 44 weeks of boceprevir (800 mg, 3 times each day) plus peginterferon and ribavirin. Patients who became anemic (levels of hemoglobin approximately ≤10 g/dL) during the study treatment period (n = 500) were assigned to groups that were managed by ribavirin dosage reduction (n = 249) or erythropoietin therapy (n = 251).ResultsRates of SVR were comparable between patients whose anemia was managed by ribavirin dosage reduction (71.5%) vs erythropoietin therapy (70.9%), regardless of the timing of the first intervention to manage anemia or the magnitude of ribavirin dosage reduction. There was a threshold for the effect on rate of SVR: patients who received
Published: 2013
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17. Adherence to assigned dosing regimen and sustained virological response among chronic hepatitis C genotype 1 patients treated with boceprevir plus peginterferon alfa-2b/ribavirin

Author: W. Deng, Bruce R. Bacon, Eric Lawitz, Margaret Burroughs, Stuart C Gordon, M. Davis, Jean-Pierre Bronowicki, Fred Poordad, Clifford A. Brass, Mark S. Sulkowski, Frank J. Dutko, Vilma Sniukiene, Eric M. Yoshida, Janice K. Albrecht, Rafael Esteban, K. Rajender Reddy, Henry Ford Hospital, University of British Columbia (UBC), Vancouver General Hospital, University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), Saint Louis University School of Medicine [St Louis], Johns Hopkins University School of Medicine [Baltimore], South Florida Center of Gastroenterology, Cedars-Sinai Medical Center, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Vall d'Hebron University Hospital [Barcelona], Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Merck & Co. Inc, and University of Pennsylvania [Philadelphia]
Subjects: Male, [SDV]Life Sciences [q-bio], Peginterferon-alfa, Hepacivirus, Gastroenterology, Polyethylene Glycols, Virological response, chemistry.chemical_compound, 0302 clinical medicine, Genotype, Medicine, Pharmacology (medical), 030212 general & internal medicine, virus diseases, Middle Aged, Viral Load, Recombinant Proteins, 3. Good health, Treatment Outcome, Peginterferon alfa-2b, RNA, Viral, 030211 gastroenterology & hepatology, Drug Therapy, Combination, Female, medicine.drug, medicine.medical_specialty, Proline, Interferon alpha-2, Antiviral Agents, Medication Adherence, 03 medical and health sciences, Chronic hepatitis, Internal medicine, Boceprevir, Ribavirin, Humans, Dosing, Retrospective Studies, Hepatology, Dose-Response Relationship, Drug, business.industry, Interferon-alpha, Hepatitis C, Chronic, digestive system diseases, Surgery, chemistry, business
Abstract: International audience; BACKGROUND:Adherence to therapeutic regimens affects the efficacy of peginterferon alfa (P) and ribavirin (R) therapy in patients with chronic hepatitis C virus genotype 1.AIM:To determine if medication adherence impacts efficacy [sustained virological response (SVR)] with triple therapy that includes boceprevir (BOC) plus P/R.METHODS:Adherence was determined in two Phase 3 clinical studies with BOC: SPRINT-2 (previously untreated patients) and RESPOND-2 (patients who failed previous therapy with P/R). Adherence to the assigned duration of the dosing regimen and adherence to the three times a day (t.d.s.) dosing interval of 7-9 h for BOC were assessed by the recording of data from patients' dosing diaries and by the amount of study drug dispensed and returned.RESULTS:Most patients (63-71%) adhered to ≥80% of their assigned treatment duration and achieved SVR rates of 86-90%. In contrast, patients who adhered to 80%) to the t.d.s. dosing interval (7-9 h) with BOC did not influence the SVR rates (SVR = 60-83%) with the exception of patients who failed previous treatment and adhered to 60% of t.d.s. dosing with boceprevir is important in patients who failed previous therapy.
Published: 2013
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18. PON3 knockout mice are susceptible to obesity, gallstone formation, and atherosclerosis

Author: Matthew D. Champion, Srinivasa T. Reddy, Johan Auwerx, David A. Ford, David N. Brindley, Peixiang Zhang, Lawrence W. Castellani, Laurent Vergnes, Aldons J. Lusis, Janet M. Yu, Asokan Devarajan, Diana M. Shih, Nassim Dali-Youcef, Carole Jamey, Karen Reue, University of California [Los Angeles] (UCLA), University of California (UC), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Les Hôpitaux Universitaires de Strasbourg (HUS), Saint Louis University School of Medicine [St Louis], University of Alberta, Ecole Polytechnique Fédérale de Lausanne (EPFL), and DALI-YOUCEF, Nassim
Subjects: Apolipoprotein E, [SDV]Life Sciences [q-bio], Gene Expression, Mitochondria, Liver, Gallstones, Kidney, Biochemistry, Cholesterol, Dietary, mitochondria-associated membrane, Mice, chemistry.chemical_compound, Intestine, Small, Hyperlipidemia, hyperlipidemia, Chemokine CCL2, Mice, Knockout, Bile acid, [SDV] Life Sciences [q-bio], mitochondria, medicine.anatomical_structure, Liver, Female, Inflammation Mediators, Biotechnology, medicine.medical_specialty, medicine.drug_class, Cholic Acid, Biology, Bile Acids and Salts, Research Communication, Apolipoproteins E, Internal medicine, Genetics, medicine, Animals, bile acid, Genetic Predisposition to Disease, Obesity, Molecular Biology, Aryldialkylphosphatase, Interleukin-6, Cholesterol, Cholic acid, cholesterol, Lipid metabolism, Atherosclerosis, Lipid Metabolism, medicine.disease, Small intestine, Diet, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, chemistry, Lipoprotein
Abstract: We report the engineering and characterization of paraoxonase-3 knockout mice (Pon3KO). The mice were generally healthy but exhibited quantitative alterations in bile acid metabolism and a 37% increased body weight compared to the wild-type mice on a high fat diet. PON3 was enriched in the mitochondria-associated membrane fraction of hepatocytes. PON3 deficiency resulted in impaired mitochondrial respiration, increased mitochondrial superoxide levels, and increased hepatic expression of inflammatory genes. PON3 deficiency did not influence atherosclerosis development on an apolipoprotein E null hyperlipidemic background, but it did lead to a significant 60% increase in atherosclerotic lesion size in Pon3KO mice on the C57BL/6J background when fed a cholate-cholesterol diet. On the diet, the Pon3KO had significantly increased plasma intermediate-density lipoprotein/LDL cholesterol and bile acid levels. They also exhibited significantly elevated levels of hepatotoxicity markers in circulation, a 58% increase in gallstone weight, a 40% increase in hepatic cholesterol level, and increased mortality. Furthermore, Pon3KO mice exhibited decreased hepatic bile acid synthesis and decreased bile acid levels in the small intestine compared with wild-type mice. Our study suggests a role for PON3 in the metabolism of lipid and bile acid as well as protection against atherosclerosis, gallstone disease, and obesity.—Shih, D. M., Yu, J. M., Vergnes, L., Dali-Youcef, N., Champion, M. D., Devarajan, A., Zhang, P., Castellani, L. W., Brindley, D. N., Jamey, C. Auwerx, J., Reddy, S. T., Ford, D. A., Reue, K., Lusis, A. J. PON3 knockout mice are susceptible to obesity, gallstone formation, and atherosclerosis.
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19. Evolving trends in novel sleep tracking and sleep testing technology publications between 2020-2022.

Author: Holfinger S, Schutte-Rodin S, Ratnasoma D, Chiang AA, Baron K, Deak M, Jerkins E, Baughn J, Gipson K, Gruber R, Miller JN, Paruthi S, Shaw S, Abbasi-Feinberg F, Olsen E, and Bandyopadhyay A
Abstract: Study Objectives: To update sleep medicine providers regarding (1) published research on the uses and performance of novel sleep tracking and testing technologies (2) the use of artificial intelligence to acquire and process sleep data and (3) research trends and gaps regarding the development and/or evaluation of these technologies., Methods: Medline and Embase electronic databases were searched for studies utilizing screening and diagnostic sleep technologies, published between 2020 and 2022 in journals focusing on human sleep. Studies' quality was determined based on the Study Design criteria of The Oxford Centre for Evidence-Based Medicine Levels of Evidence., Results: 96 of 3849 articles were included. Most studies were adult performance evaluation (validation) studies, often comparing a novel technology to polysomnography. Sleep tracker publications tended to be USA-based, non-industry funded, performance studies on healthy adults using non-FDA (Food and Drug Administration) cleared technologies. Sleep apnea testing technologies were more frequently industry-funded and FDA-cleared. All studied technologies utilized software with an algorithm and/or artificial intelligence. Few studies used randomized control designs, or accounted for recruitment/attrition biases associated with participants' age, race/ethnicity, or comorbid health conditions., Conclusions: Evidence-based publications have not kept pace with the proliferation and landscape of' consumer and clinical sleep technologies. Due to the variance in technologies used within sleep research, careful review of the software used within studies is recommended. Future publications may fill identified gaps by including underrepresented populations, maintaining independence from industry, and through rigorous study design., (© 2025 American Academy of Sleep Medicine.)
Published: 2025
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20. Osteochondral Allograft Transplantation as a Salvage Procedure After Failed Index Cartilage Surgery of the Knee: A Systematic Review.

Author: Gopinatth V, Tartibi S, Smith MV, Matava MJ, Brophy RH, and Knapik DM
Abstract: Background: Osteochondral allograft transplantation (OCA) is well established as a viable chondral restoration procedure for the treatment of symptomatic, focal chondral defects of the knee. The efficacy of secondary OCA in the setting of failed index cartilage repair or restoration is poorly understood., Purpose: To evaluate radiographic and clinical outcomes, failures, and reoperations after OCA after failed index cartilage repair or restoration of the knee., Study Design: Systematic review; Level of evidence, 4., Methods: A systematic review was conducted in accordance with the 2020 PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A literature search was conducted by querying PubMed, MEDLINE, Scopus, the Cochrane Database for Systematic Reviews, and the Cochrane Central Register for Controlled Trials databases from inception through September 2023 to identify studies reporting on outcomes of patients undergoing OCA after failed index chondral repair or restoration., Results: A total of 6 studies, entailing 349 patients, met inclusion criteria. The mean patient age was 34.6 ± 10.2 years. The mean chondral defect size at the time of secondary OCA was 5.8 cm 2 (range, 4.0-9.5 cm 2 ), and the most common defect location was the medial femoral condyle (53.6%; n = 171/319). The most common index chondral procedures were marrow stimulation (73.8%; n = 256/347 patients), OCA (11.8%; n = 41/347), and autologous chondrocyte implantation (4.9%; n = 17/347). The overall failure rate after secondary OCA was 16.6% (95% CI, 8.8%-24.4%). The overall reoperation rate was 42.8% (95% CI, 31.7%-53.9%). Failure and reoperation rates were associated with increasing chondral defect size ( P < .01). Defects 9-10 cm 2 had a reoperation rate of 67% and a failure rate of 39%. The 5-year survival rate after secondary OCA was 79% to 87.8%, and the 10-year survival rate was 61% to 82%. A total of 42 clinical outcome scores were reported, and 71.0% (n = 22/31) of patient-reported outcome measures yielded significant improvement from preoperative to postoperative levels for patients undergoing secondary OCA., Conclusion: After index chondral surgery, the overall failure rate after secondary OCA was 16.6%, with an overall reoperation rate of 42.8%. The majority of clinical outcomes reported suggest improvement when compared with preoperative values. Larger chondral defects may be associated with higher rates of failure and reoperation., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: M.V.S. has received speaking, education, and hospitality payments from Arthrex; education and hospitality payments from Elite Orthopedics; and hospitality payments from Medical Device Business Services. M.J.M. has received consulting, speaking, and hospitality payments from Arthrex; education payments from Elite Orthopedics; and consulting and hospitality payments from Heron Therapeutics and Pacira Pharmaceuticals. R.H.B. has received support for education and hospitality payments from Elite Orthopedics. D.M.K. has received support for education from Smith & Nephew, Elite Orthopedics, and Medwest Associates; hospitality payments from Arthrex, Encore Medical, Stryker, and Smith & Nephew; honoraria from Encore Medical; and a grant from Arthrex. AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto.
Published: 2025
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21. Replacement of a single residue changes the primary specificity of thrombin.

Author: Rossi AD, Deavila S, Mohammed BM, Korolev S, and Di Cera E
Abstract: Background: Thrombin prefers substrates carrying Arg at the site of cleavage (P1) because of the presence of D189 in the primary specificity (S1) pocket but can also cleave substrates carrying Phe at P1. The structural basis of this property is unknown., Objective: Solve the X-ray structure of thrombin bound to a ligand carrying Phe at P1 and investigate the effects of replacing D189., Methods: X-ray crystallography is used to solve the structure of thrombin bound to the irreversible inhibitor H-D-Phe-Pro-Phe-CH 2 Cl (PPPCK). Residue D189 is mutated to Ala, Lys, Phe and Ser., Results: The X-ray structure of the thrombin-PPPCK complex is solved at 2.5 Å resolution and compared to the structure of thrombin bound to H-D-Phe-Pro-Arg-CH 2 Cl (PPACK). PPPCK binds to thrombin in a conformation similar to that of PPACK, but Phe at P1 makes no contacts with D189. Replacement of D189 with Ala, Lys, Phe or Ser reverses both substrate preference and stability enhancement from Arg to Phe., Conclusions: D189 in the S1 pocket confers thrombin "trypsin-like" specificity for Arg at P1. However, the S1 pocket is wide enough to also enable "chymotrypsin-like" specificity for Phe at P1. Consistent with these structural features, a single amino acid replacement (D189A) switches thrombin specificity from trypsin-like to chymotrypsin-like, converting the substrate preference from H-D-Phe-Pro-Arg-p-nitroanilide to H-D-Phe-Pro-Phe-p-nitroanilide and preferential stability enhancement from PPACK to PPPCK. The observation that thrombin specificity is controlled mainly by a single residue establishes a new paradigm in the field of trypsin-like proteases., (Copyright © 2025. Published by Elsevier Inc.)
Published: 2025
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22. Unlocking Therapeutic Potential: Mesenchymal Stem Cells-derived Exosomes in IUA Treatment, Current Status and Perspectives.

Author: Rajabloo Y, Al-Asady AM, Avan A, Khazaei M, Ryzhikov M, and Hassanian SM
Abstract: Intrauterine adhesion (IUA) is a condition caused by damage to the basal uterine layer which can lead to partial or full occlusion of the uterine cavity. Although traditional treatment options have been useful in mild and moderate cases, they have been unsatisfactory in severe IUA cases. Therefore, it is essential to improve the treatment strategies of IUA. Recent studies have demonstrated that Mesenchymal stem cells (MSCs) exert their therapeutic effects via the paracrine secretion of several substances including extracellular vesicles (EV) also called exosomes. MSC-derived exosomes (MSC-Exos) do not have the limitations of MSCs including immunogenicity and tumorigenicity. However, exosomes have limitations in terms of identification, isolation, purification, and origin. The clinical application of exosomes requires quality control and increased standardization in isolation and culture serum. This review summarizes therapeutic potentials of MSC-Exos and explores their potential clinical implications as diagnostic, therapeutic targets as well as prognostic markers in managing IUA., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Published: 2025
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23. Anti-neuraminidase and anti-hemagglutinin stalk responses to different influenza a(H7N9) vaccine regimens.

Author: El Sahly HM, Anderson EJ, Jackson LA, Neuzil KM, Atmar RL, Bernstein DI, Chen WH, Creech CB, Frey SE, Goepfert P, Meier J, Phadke V, Rouphael N, Rupp R, Stapleton JT, Spearman P, Walter EB, Winokur PL, Yildirim I, Williams TL, Oshinsky J, Coughlan L, Nijhuis H, Pasetti MF, Krammer F, Stadlbauer D, Nachbagauer R, Tsong R, Wegel A, and Roberts PC
Abstract: Introduction: Pandemic influenza vaccine development focuses on the hemagglutinin (HA) antigen for potency and immunogenicity. Antibody responses targeting the neuraminidase (NA) antigen, or the HA stalk domain have been implicated in protection against influenza. Responses to the NA and HA-stalk domain following pandemic inactivated influenza are not well characterized in humans., Material and Methods: In a series of clinical trials, we determine the vaccines' NA content and demonstrate that NA inhibition (NAI) antibody responses increase in a dose-dependent manner following a 2-dose priming series with AS03-adjuvanted influenza A(H7N9) inactivated vaccine (A(H7N9) IIV). NAI antibody responses also increase with interval extension of the 2-dose priming series or following a 5-year delayed boost with a heterologous adjuvanted A(H7N9) IIV. Neither concomitant seasonal influenza vaccination given simultaneously or sequentially, nor use of heterologous A(H7N9) IIVs in the 2-dose priming series had an appreciable effect on NAI antibody responses. Anti-HA stalk antibody responses were minimal and not durable., Conclusions: We provide evidence for strategies to improve anti-neuraminidase responses which can be further standardized for pandemic preparedness., Clinical Trial Registry Numbers: NCT03312231, NCT03318315, NCT03589807, NCT03738241., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2025 Elsevier Ltd. All rights reserved.)
Published: 2025
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24. Survey of Laboratory Stewardship Governance at US Academic Medical Centers.

Author: Eby CS, Al-Hammadi N, Dodds K, Sunkavalli D, and Gronowski AM
Subjects: Humans, Surveys and Questionnaires, United States, Leadership, Laboratories, Clinical organization & administration, Academic Medical Centers organization & administration, Academic Medical Centers statistics & numerical data
Abstract: Background: Efforts to appropriately utilize laboratory tests have been underway for several decades. However, limited information is available regarding the status of laboratory stewardship at academic medical centers. Prior to initiating a laboratory stewardship committee, a study was initiated to gain insights from peer institutions., Methods: An online REDCap survey was created and emailed to US pathology department leaders at 94 academic medical centers., Results: Response rate was 40%. Sixty-eight percent (n = 26) of respondents indicated that they have a laboratory stewardship committee. There was variability among academic medical institutions regarding governance, committee structure and responsibilities, and assessment of laboratory stewardship committee performance. There was consensus for inclusion of: hospital administration and clinical leadership; informatics (IT) support, and a multidisciplinary clinical team combined with laboratory medicine expertise. Of the 32% (n = 12) without a committee, 4 started one but found it unsustainable, and 6 were unsuccessful at starting a program. Respondents without a current laboratory stewardship program cited lack of leadership support, insufficient management and IT resources, and unclear vision and goals as major factors. Fifty-eight percent of those without a laboratory stewardship committee predicted their hospital would establish one within the next 5 years., Conclusions: Survey results provide insights into the status of laboratory stewardship efforts at peer institutions. Awareness of the structural and leadership components critical to successful and sustained initiatives will improve the quality and value of clinical laboratory services., (© Association for Diagnostics & Laboratory Medicine 2025. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)
Published: 2025
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25. Topical Netarsudil in Childhood Glaucoma: A Systematic Review.

Author: Shaikh O, Kuziez L, Saeedi OJ, Abbasian J, and Elhusseiny AM
Abstract: Purpose: To evaluate the effectiveness and safety of topical netarsudil 0.02% in managing childhood glaucoma., Methods: A literature search in the electronic databases of PubMed CENTRAL, Google Scholar, EMBASE, the Register of Controlled Trials, and Ovid MEDLINE from January 2017 to August 2023 using one or a combination of the following terms: "netarsudil," "rhopressa," "Rho-kinase," "pediatric glaucoma," "childhood glaucoma," "intraocular pressure" was conducted., Results: Eight publications (four retrospective studies, one prospective study, and three case reports) were identified evaluating the outcomes of topical netarsudil in childhood glaucoma. Six publications were conducted in the United States, and two publications were conducted in India. Studies included a heterogeneous cohort of primary and secondary childhood glaucoma with a variable range of follow-up (1 week-26 months). The mean IOP reduction after the initiation of topical netarsudil 0.02% in childhood glaucoma patients varies from 0.8 ± 13.2 to 12.0 ± 0.0 mmHg. The most common ocular adverse event was conjunctival hyperemia, seen in 27 out of 82 eyes (32.9%), followed by corneal honeycombing/reticular epithelial edema, seen in 13 out of 82 eyes (15.9%)., Conclusion: Limited literature is currently available on using topical netarsudil in childhood glaucoma. However, in children with refractory glaucoma on maximum topical medications, netarsudil may serve as an adjunctive treatment option, potentially delaying the need for further surgical interventions in some patients. Careful corneal examination is needed before and after initiation of netarsudil treatment for early detection of corneal adverse events that may compromise the vision.
Published: 2025
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26. N-Linked Fucosylated Glycans Are Biomarkers for Prostate Cancer with a Neuroendocrine and Metastatic Phenotype.

Author: Ippolito JE, Hartig JP, Bejar K, Nakhoul H, Sehn JK, Weimholt C, Grimsley G, Nunez E, Trikalinos NA, Chatterjee D, Kim EH, Mehta AS, Angel PM, Troyer DA, Leach RJ, Corey E, Wu JD, and Drake RR
Subjects: Male, Humans, Animals, Adenocarcinoma metabolism, Adenocarcinoma pathology, Mice, Fucose metabolism, Neoplasm Metastasis, Glycosylation, Phenotype, Prostatic Neoplasms metabolism, Prostatic Neoplasms pathology, Polysaccharides metabolism, Biomarkers, Tumor metabolism
Abstract: Prostate cancer is a heterogeneous disease with a spectrum of pathology and outcomes ranging from indolent to lethal. Although there have been recent advancements in prognostic tissue biomarkers, limitations still exist. We leveraged matrix-assisted laser desorption/ionization imaging of formalin-fixed, paraffin embedded prostate cancer specimens to determine if N-linked glycans expressed in the extracellular matrix of lethal neuroendocrine prostate cancer were also expressed in conventional prostate adenocarcinomas that were associated with poor outcomes. We found that N-glycan fucosylation was abundant in neuroendocrine prostate cancer as well as adenocarcinomas at the time of prostatectomy that eventually developed recurrent metastatic disease. Analysis of patient-derived xenografts revealed that this fucosylation signature was enriched differently across metastatic disease organ sites, with the highest abundance in liver metastases. These data suggest that N-linked fucosylated glycans could be an early tissue biomarker for poor prostate cancer outcomes. Implications: These studies identify that hyper-fucosylated N-linked glycans are enriched in neuroendocrine prostate cancer and conventional prostate adenocarcinomas that progress to metastatic disease, thus advancing biomarker discovery and providing insights into mechanisms underlying metastatic disease., (©2024 The Authors; Published by the American Association for Cancer Research.)
Published: 2025
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27. The Application of Hydrogels in the Treatment of Intrauterine Adhesions.

Author: Rajabloo Y, Al-Asady AM, Akbarzadeh H, Avan A, Khazaei M, Ryzhikov M, and Hassanian SM
Abstract: Intrauterine Adhesions (IUA) are a significant cause of infertility and miscarriage, often resulting from trauma to the endometrium. While hysteroscopic adhesiolysis is the primary treatment, the use of hydrogels as anti-adhesion barriers and drug delivery systems is gaining traction for improving patient outcomes. This review aims to explore various hydrogel types, their role in tissue repair, and the integration of stem cell therapy. Recent advancements in biomaterial scaffolds have demonstrated potential in preventing adhesion recurrence and promoting endometrial regeneration. These emerging treatments provide promising avenues for enhancing the efficacy of traditional therapies in IUA management., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
Published: 2025
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28. Global consensus on optimal exercise recommendations for enhancing healthy longevity in older adults (ICFSR).

Author: Izquierdo M, de Souto Barreto P, Arai H, Bischoff-Ferrari HA, Cadore EL, Cesari M, Chen LK, Coen PM, Courneya KS, Duque G, Ferrucci L, Fielding RA, García-Hermoso A, Gutiérrez-Robledo LM, Harridge SDR, Kirk B, Kritchevsky S, Landi F, Lazarus N, Liu-Ambrose T, Marzetti E, Merchant RA, Morley JE, Pitkälä KH, Ramírez-Vélez R, Rodriguez-Mañas L, Rolland Y, Ruiz JG, Sáez de Asteasu ML, Villareal DT, Waters DL, Won Won C, Vellas B, and Fiatarone Singh MA
Subjects: Humans, Aged, Aging physiology, Consensus, Quality of Life, Aged, 80 and over, Life Style, Healthy Aging physiology, Exercise physiology, Longevity physiology
Abstract: Aging, a universal and inevitable process, is characterized by a progressive accumulation of physiological alterations and functional decline over time, leading to increased vulnerability to diseases and ultimately mortality as age advances. Lifestyle factors, notably physical activity (PA) and exercise, significantly modulate aging phenotypes. Physical activity and exercise can prevent or ameliorate lifestyle-related diseases, extend health span, enhance physical function, and reduce the burden of non-communicable chronic diseases including cardiometabolic disease, cancer, musculoskeletal and neurological conditions, and chronic respiratory diseases as well as premature mortality. Physical activity influences the cellular and molecular drivers of biological aging, slowing aging rates-a foundational aspect of geroscience. Thus, PA serves both as preventive medicine and therapeutic agent in pathological states. Sub-optimal PA levels correlate with increased disease prevalence in aging populations. Structured exercise prescriptions should therefore be customized and monitored like any other medical treatment, considering the dose-response relationships and specific adaptations necessary for intended outcomes. Current guidelines recommend a multifaceted exercise regimen that includes aerobic, resistance, balance, and flexibility training through structured and incidental (integrated lifestyle) activities. Tailored exercise programs have proven effective in helping older adults maintain their functional capacities, extending their health span, and enhancing their quality of life. Particularly important are anabolic exercises, such as Progressive resistance training (PRT), which are indispensable for maintaining or improving functional capacity in older adults, particularly those with frailty, sarcopenia or osteoporosis, or those hospitalized or in residential aged care. Multicomponent exercise interventions that include cognitive tasks significantly enhance the hallmarks of frailty (low body mass, strength, mobility, PA level, and energy) and cognitive function, thus preventing falls and optimizing functional capacity during aging. Importantly, PA/exercise displays dose-response characteristics and varies between individuals, necessitating personalized modalities tailored to specific medical conditions. Precision in exercise prescriptions remains a significant area of further research, given the global impact of aging and broad effects of PA. Economic analyses underscore the cost benefits of exercise programs, justifying broader integration into health care for older adults. However, despite these benefits, exercise is far from fully integrated into medical practice for older people. Many healthcare professionals, including geriatricians, need more training to incorporate exercise directly into patient care, whether in settings including hospitals, outpatient clinics, or residential care. Education about the use of exercise as isolated or adjunctive treatment for geriatric syndromes and chronic diseases would do much to ease the problems of polypharmacy and widespread prescription of potentially inappropriate medications. This intersection of prescriptive practices and PA/exercise offers a promising approach to enhance the well-being of older adults. An integrated strategy that combines exercise prescriptions with pharmacotherapy would optimize the vitality and functional independence of older people whilst minimizing adverse drug reactions. This consensus provides the rationale for the integration of PA into health promotion, disease prevention, and management strategies for older adults. Guidelines are included for specific modalities and dosages of exercise with proven efficacy in randomized controlled trials. Descriptions of the beneficial physiological changes, attenuation of aging phenotypes, and role of exercise in chronic disease and disability management in older adults are provided. The use of exercise in cardiometabolic disease, cancer, musculoskeletal conditions, frailty, sarcopenia, and neuropsychological health is emphasized. Recommendations to bridge existing knowledge and implementation gaps and fully integrate PA into the mainstream of geriatric care are provided. Particular attention is paid to the need for personalized medicine as it applies to exercise and geroscience, given the inter-individual variability in adaptation to exercise demonstrated in older adult cohorts. Overall, this consensus provides a foundation for applying and extending the current knowledge base of exercise as medicine for an aging population to optimize health span and quality of life., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)
Published: 2025
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29. Recent advances in Alzheimer's disease therapy: clinical trials and literature review of novel enzyme inhibitors targeting amyloid precursor protein.

Author: Antony D, Sheth P, Swenson A, Smoller C, Maguire K, and Grossberg G
Subjects: Humans, Animals, Drug Development, Amyloid beta-Peptides metabolism, Amyloid beta-Peptides antagonists & inhibitors, Molecular Targeted Therapy, Alzheimer Disease drug therapy, Alzheimer Disease metabolism, Amyloid Precursor Protein Secretases antagonists & inhibitors, Amyloid Precursor Protein Secretases metabolism, Amyloid beta-Protein Precursor metabolism, Enzyme Inhibitors pharmacology, Enzyme Inhibitors therapeutic use
Abstract: Introduction: Amyloid precursor protein (APP) plays a central role in the pathophysiology of Alzheimer's disease (AD). The accumulation of beta-amyloid protein is believed to be a crucial step in the development of AD. Therefore, understanding the complex biology of APP and its various cleavage products may be useful for developing effective therapeutic strategies for AD., Areas Covered: The amyloidogenic pathway of APP processing involves proteolytic cleavage by two prominent secretases, γ-Secretase and β-secretase. In the late 2000s, multiple pharmaceutical drugs that inhibited γ-Secretase and β-Secretase were synthesized, some of which advanced to human clinical trials. Unfortunately, neither γ-Secretase nor β-secretase inhibitors have been approved by the FDA due to both lack of efficacy and concerns for serious side effects., Expert Opinion: While targeting of Aβ accumulation through secretase inhibitors was halted due to severe side effects, γ-Secretase modulators (GSMs) have arisen as a potential alternative approach. First-generation GSMs could modulate γ-secretase activity without affecting Notch cleavage. However, to improve potency and brain penetration, second-generation GSMs were developed to reduce levels of the amylogenic form of Aβ, Aβ42, without affecting the NOTCH signaling pathway. Several of these drugs have progressed to clinical trials, although with mixed results. The development of GSM's continues to serve as a potentially safer approach to modulating Aβ production in AD treatment.
Published: 2025
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30. Endovascular thrombectomy for distal medium vessel occlusions: A literature review.

Author: Aldaher B, Behera A, Morsi RZ, Adra S, Desai H, Kothari SA, Thind S, Chahine A, Carrión-Penagos J, Baskaran A, Rana R, Armbrecht ES, Siegler JE, Coleman ER, Brorson JR, Mendelson SJ, Mansour A, Prabhakaran S, and Kass-Hout T
Subjects: Humans, Treatment Outcome, Risk Factors, Male, Thrombectomy adverse effects, Thrombectomy instrumentation, Endovascular Procedures instrumentation, Endovascular Procedures adverse effects
Abstract: Background: There is a lack of substantial evidence supporting the safety and effectiveness of endovascular thrombectomy in treating distal medium vessel occlusions (DMVOs)., Objective: To summarize the current evidence regarding endovascular thrombectomy for DMVOs., Methods: We conducted a narrative review of key articles related to the diagnosis and management of DMVOs. We manually searched PubMed and Google Scholar from January 2010 to July 2023, and only included articles published in the English language., Results: While diagnosing and treating DMVOs is tricky due to access limitations and potential limited benefit from mechanical clot removal, recent improvements in catheter and retrieval technology suggest that endovascular thrombectomy might be a potential treatment option. However, more high-quality research is needed to confirm its effectiveness for DMVOs., Conclusion: Experts disagree on how to classify DMVOs and what the best mode of endovascular treatment is., Competing Interests: Declaration of competing interest We declare no competing interests., (Copyright © 2024. Published by Elsevier Inc.)
Published: 2025
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31. Cholate Shunt, Oral Cholate Challenge and Endoscopic Lesions of Portal Hypertension: The SHUNT-V Study.

Author: Shiffman M, Reddy KR, Leise MD, Qureshi K, Smith AD, Helmke S, Kittelson J, McRae MP, Imperial JC, and Everson GT
Subjects: Humans, Male, Female, Middle Aged, Aged, Severity of Illness Index, Adult, Obesity complications, Pseudotumor Cerebri physiopathology, Pseudotumor Cerebri complications, Administration, Oral, Hypertension, Portal complications, Esophageal and Gastric Varices etiology, Liver Cirrhosis complications
Abstract: Background: The accuracy of current criteria for ruling out large oesophageal varices (LEV) and other endoscopic lesions of portal hypertension (PH) may be compromised by obesity and MASLD/MASH., Aims: In the US multicentre SHUNT-V study, we evaluated the disease severity index (DSI) for detecting LEV and other lesions of PH at endoscopy., Methods: Subjects were adults with compensated cirrhosis scheduled for endoscopy to screen for varices. DSI was calculated from clearances of labelled cholates after oral and intravenous administration. DSI ≤ 18.3 was evaluated as a cut-off for ruling out LEV with acceptance criteria of negative likelihood ratio < 0.52 and sensitivity > 85%., Results: SHUNT-V enrolled 306 subjects; 275 had both DSI and endoscopy, and 238 had Child-Pugh A cirrhosis (52.1% MASLD/MASH, 25.2% chronic hepatitis C and 15.6% alcoholic liver disease; 87% were overweight, 64% were obese and 54% had diabetes). AUROCs for DSI ranged from 0.81 to 0.82 for LEV and 0.79 to 0.80 for all significant PH lesions. DSI 18.3 had sensitivity 96.3%-100% for LEV and 97.3%-100% for all significant PH lesions. If DSI ≤ 18.3 were used as the sole determinant to defer EGD, 27%-35% of EGDs could have been avoided with 0%-3.7% of LEV and 0%-2.7% of all significant PH lesions missed., Conclusions: HepQuant DSI predicts the likelihood of LEV and significant PH lesions across a spectrum of patient characteristics and disease aetiologies. DSI, based on liver function and portal-systemic shunting, can aid in the decision to defer endoscopy for varices in patients with Child-Pugh A cirrhosis., Trial Registration: The SHUNT-V study was registered at ClinicalTrials.gov (NCT03583996)., (© 2024 The Author(s). Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)
Published: 2025
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32. Screen Time Before 2 Years of Age and Risk of Autism at 12 Years of Age.

Author: Lin PI, Wu WT, and Guo YL
Published: 2025
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33. The implementation of molecular tumor profiling in the practice of pediatric cancer pathology: The pathologists' experience.

Author: Gestrich CK, Kreiger P, Surrey L, Besmer S, Lopez-Terrada D, and Church AJ
Subjects: Humans, Child, High-Throughput Nucleotide Sequencing, Surveys and Questionnaires, Pediatrics, Pathology, Molecular methods, Practice Patterns, Physicians' standards, Neoplasms genetics, Neoplasms pathology, Pathologists
Abstract: Background: The increased accessibility and utilization of molecular testing including next-generation sequencing (NGS) has impacted the practice of pediatric pathology, with diagnostic, prognostic, and therapeutic implications for our patients. This survey is the first to describe the utilization of molecular testing in the routine practice of pediatric pathology for the care of children with known or suspected solid tumors., Procedure: The Society for Pediatric Pathology Practice Committee distributed a survey to our membership asking 25 questions about training, practice setting, molecular ordering practices, and barriers to testing., Results: Seventy-five pathologists responded to the survey. The survey provides valuable insight into the current use of molecular testing for the care of children with known or suspected solid tumors. Most respondents reported that they are increasingly using a variety of molecular techniques, with increased use over time, and that NGS is useful., Conclusions: These results highlight a variety of barriers to molecular testing, including cost, insurance coverage, turnaround time, limitations of available assays (including limited coverage of pediatric-specific alterations), and difficulty in determining the most appropriate test to order. These data may be useful in supporting pediatric pathologists in their practice., (© 2024 Wiley Periodicals LLC.)
Published: 2025
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34. Unveiling Cancer-Related Metaplastic Cells in Both Helicobacter pylori Infection and Autoimmune Gastritis.

Author: Hoft SG, Brennan M, Carrero JA, Jackson NM, Pretorius CA, Bigley TM, Sáenz JB, and DiPaolo RJ
Subjects: Humans, Animals, Mice, Disease Models, Animal, Female, Transcriptome, Biopsy, Male, Mice, Inbred C57BL, Single-Cell Analysis, Helicobacter Infections microbiology, Helicobacter Infections pathology, Helicobacter Infections complications, Helicobacter Infections immunology, Metaplasia, Stomach Neoplasms microbiology, Stomach Neoplasms pathology, Stomach Neoplasms immunology, Helicobacter pylori pathogenicity, Gastritis microbiology, Gastritis pathology, Gastritis immunology, Autoimmune Diseases microbiology, Autoimmune Diseases pathology, Gastric Mucosa pathology, Gastric Mucosa microbiology, Gastric Mucosa immunology
Abstract: Background & Aims: Gastric metaplasia may arise as a consequence of chronic inflammation and is associated with an increased risk of gastric cancer development. Although Helicobacter pylori (Hp) infection and autoimmune gastritis (AIG) both induce gastric metaplasia, possible distinctions in resulting metaplastic cells and their respective cancer risks requires further investigation., Methods: Using both mouse models and human participants, we scrutinized the metaplasia originating from Hp infection and AIG. Gastric pathology and metaplasia were examined through histopathologic assessment. Molecular features of metaplastic cells were defined using single-cell transcriptomics in murine models of Hp infection and AIG, as well as in human biopsy specimens from patients with Hp infection and AIG. Expression of a newly defined cancer-related metaplastic biomarker was confirmed through immunofluorescence., Results: Metaplasia in Hp infection and AIG displayed comparable histopathologic and transcriptional features. Diverse metaplastic subtypes were identified across both disease settings, with subtle differences in the prevalence of certain subtypes between inflammatory contexts. Notably, Hp infection did not drive a unique metaplastic cell phenotype. One metaplastic subtype, which resembled incomplete intestinal metaplasia and shared transcriptional features with gastric cancer, was identified in both diseases. This cancer-like metaplastic subtype was characterized by expression of the cancer-associated biomarker ANPEP/CD13., Conclusion: Both Hp infection and AIG trigger a diverse array of metaplastic cell types. Identification of a cancer-related metaplastic cell uniquely expressing ANPEP/CD13, present in both Hp- and AIG-induced gastritis, indicates the carcinogenic capacity of both diseases. This discovery can guide early detection and risk stratification for patients with chronic gastritis., (Copyright © 2025 AGA Institute. Published by Elsevier Inc. All rights reserved.)
Published: 2025
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35. The Impact of Palliative Care Consultation on Aggressive Medical Interventions in End-of-life Among Patients with Metastatic Breast Cancer: Insights from the U.S. National Patient Sample.

Author: Zhang Z, Lovell A, Subramaniam DS, and Hinyard L
Subjects: Humans, Female, Middle Aged, Retrospective Studies, United States, Aged, Adult, Aged, 80 and over, Cohort Studies, Neoplasm Metastasis, Breast Neoplasms therapy, Breast Neoplasms pathology, Palliative Care statistics & numerical data, Terminal Care statistics & numerical data, Referral and Consultation statistics & numerical data
Abstract: Background: Advancement in treatment has led to prolonged survival and a rising number of women living with metastatic breast cancer (MBC) in the United States. Due to its high symptom burden, it is recommended that palliative care be integrated into the standard care to help improve quality of life. However, little is known about the use of palliative care among MBC patients in the nation., Objectives: To determine utilization of palliative care consult (PCC) after metastasis and the influence of PCC on healthcare utilization in the end of life among women living with MBC in the US., Methods: This retrospective cohort study examined a national electronic health record database to quantify the PCC use after metastasis diagnosis until death and the associations of PCC with Emergency Department (ED), Intensive Care Unit (ICU), and chemotherapies in the end-of-life women (age ≥ 18 years) living with MBC., Results: From a cohort of 2615 deceased MBC patients, 37% received PCC in the last 6 months of life. Patients who had received PCC in the end-of-life were more likely to be hospitalized, admitted to ED and ICU, and receive chemotherapies in the last 60 days before death. However, patients who had received end-of-life PCC had less hospital and ED visits and received less chemotherapies after PCC initiated., Conclusion: While PCC can reduce end-of-life aggressive interventions, it was underutilized among patients with MBC in the end-of-life. A myriad of clinical and patient factors may still challenge timely consultation. We urge for future endeavors in developing strategies to remove barriers in the implementation, especially earlier in the disease course, to assure timely PC treatments and reduce discomfort amid aggressive interventions for MBC., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Published: 2025
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36. Changes in Emergency Department and Inpatient Encounters for Falls after the Onset of the COVID-19 Pandemic.

Author: Lach HW, Salas J, and Scherrer JF
Subjects: Humans, Female, Male, Aged, Middle Aged, Aged, 80 and over, SARS-CoV-2, Hospitalization statistics & numerical data, Inpatients statistics & numerical data, Pandemics, Accidental Falls statistics & numerical data, Accidental Falls prevention & control, COVID-19 epidemiology, Emergency Service, Hospital statistics & numerical data
Abstract: Objective: This study investigates changes in clinical encounters due to falls before and after the onset of the COVID-19 pandemic., Methods: De-identified health record data from a large mid-western health system was used to examine the frequency of emergency department (ED) and inpatient (IP) encounters for falls by month among adults age 50+ ( N = 485, 886 patients) using joinpoint regression analysis. Also, overall rates before and during the pandemic were compared using log-binomial models., Results: Fall rates increased following the onset of the COVID-19 pandemic for IP encounters but not for ED encounters. There were no differences by age, gender, race, or nSES. Monthly IP fall rates increased by 0.68% per month both before and after the onset of the COVID-19 pandemic., Conclusion: Pandemics may occur in the future, and interventions are needed to prevent falls in older adults during the next public health emergency., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Published: 2025
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37. Evaluation and management of pediatric refractory constipation: Recommendations from the NASPGHAN neurogastroenterology and motility committee.

Author: Kilgore AL, Rogers Boruta MK, Ambartsumyan L, Suarez RG, Patel D, Wood RJ, Darbari A, and Rodriguez L
Abstract: Refractory constipation (RC) in pediatric patients should be recognized as a distinct condition with long-term impacts on patient and family quality of life. RC requires a more targeted diagnostic evaluation and complex management strategy that may involve management by pediatric neurogastroenterology and motility specialists and multidisciplinary teams including surgeons. Currently, there is a lack of a clear definition, evaluation, and management strategies for RC. This is the first North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition position paper to address pediatric RC regarding its definition, evaluation, and management., (© 2024 European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition.)
Published: 2024
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38. Suicide Deaths by Occupation Skill Level and Educational Attainment in the US.

Author: Messias E, Azasu EK, Nayeem N, Lin PI, and Grucza R
Abstract: Objective: Estimate the association between suicide deaths and both occupation skill level and educational attainment in the US., Methods: Suicide deaths, employment, education and demographic data from the 2021 National Center for Health Statistics Multiple Cause of Death Files, for ages 18-64 with a lifetime history of employment were combined with comparable participants from the 2020-2022 Current Population Survey. Outcomes of interest were associations between suicide death and occupational skill level, assessed as a five-level variable, and educational attainment. Logistic regression models were used to estimate these associations before and after adjusting for educational attainment, age and sex, in each racial/ethnic sub-population., Results: We found a significant gradient in suicide death across occupation skill levels, with lower-skill occupations associated with higher suicide rates than higher-skill occupations. This gradient was more pronounced among non-Hispanic White (NHW) people and Non-Hispanic Black (NHB) people than Hispanic people. However, upon controlling for educational attainment, this association was attenuated, indicating that the initial link was likely confounded by education., Conclusions: The results suggest that educational attainment is a more robust predictor of suicide risk than occupation skill level. Targeted interventions addressing educational and ethnic disparities within higher-risk occupational groups can mitigate suicide risk., (© The Author(s) [2024]. Published by Oxford University Press.)
Published: 2024
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39. Resolving Lipoxin A 4 : Endogenous Mediator or Exogenous Anti-Inflammatory Agent?

Author: McGuffee RM, Luetzen MA, and Ford DA
Published: 2024
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40. Synthesis and in vitro evaluation of novel compounds and discovery of a promising iodine-125 radioligand for purinergic P2X7 receptor (P2X7R).

Author: Qiu L, Wang J, Tewari M, Rensing DT, Egan TM, Perlmutter JS, and Tu Z
Abstract: The purinergic P2X ligand-gated ion channel 7 receptor (P2X7R) plays a critical role in various inflammatory processes and other diseases. Fast determination of compounds P2X7R binding potency and discovery of a promise PET radiotracer for imaging P2X7R require a P2X7R suitable radioligand for radioactive competitive binding assay. Herein, we designed and synthesized thirteen new P2X7R ligands and determined the in vitro binding potency. The fluorescence screening assay identified the iodide compound 1c with high potency and specificity toward P2X7R with an IC 50 of 0.25 ± 0.05 nM. Therefore, 1c was 125 I-labeled to afford [ 125 I]1c with a good radiochemical yield (44 ± 12 %, n = 3) and high radiochemical purity (>95 %). Radioligand saturation binding assay showed that [ 125 I]1c specifically bound to human P2X7R with high affinity (K d = 1.68 nM and B max = 94 fmol/mg). A radioactive high throughput binding assay using [ 125 I]1c for our new compounds demonstrated that the imidazole compounds 1b, 1c, and 1d exhibited high inhibition for >70 %, while the analogues of GSK314181A exhibited low inhibition for <35 %. In addition, our radioligand competitive binding assays using [ 125 I]1c demonstrated that 1b, 1c, and 1d have high potency with IC 50 values of 7.91 ± 0.22, 7.06 ± 1.68, and 7.16 ± 0.41 nM toward P2X7R, respectively.Together, compounds 1b, 1c, and 1d are highly potent for P2X7R, and [ 125 I]1c has great potential to be a radioligand for screening P2X7R binding potency of the new compounds and investigating the P2X7R expression in animal models of human disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
Published: 2024
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41. The Applicability of the Interpersonal Psychological Theory of Suicide Behavior Among Junior High School Students in the Greater Accra Region of Ghana.

Author: Azasu EK, Quarshie EN, Messias E, and Joe S
Abstract: Background: The interpersonal-psychological theory of suicidal behavior (IPTSB) is widely applied to explain non-fatal suicide behaviors, but yet to be tested empirically with a Ghanaian sample., Aims: Using a total of 800 junior high school students (JHS) in the Greater Accra Region of Ghana, this study tests the utility of the IPTSB with the aim of having a better understanding of how suicide behavior is occurring among this young generation of Ghanaians., Materials and Methods: The study used the WHO-CIDI's self-reported measures on suicide behavior and the Interpersonal needs questionnaire, which measures the elements of the IPTSB. Structural equation modeling was performed using Mplus to test the overall fit of the model as well as associations among the predictor variables and outcome variables., Results: The study found the IPTSB was significant for explaining 12-month and lifetime suicide behaviors in the sample. Also, 12-month suicide attempt was significantly associated with increased 12-month suicide ideation, increased acquired capability and increased perceived burdensomeness. In addition, 12-month suicide ideation was significantly associated with increased thwarted belongingness and increased perceived burdensomeness., Discussion and Conclusion: This study provides new information for clinicians and policy makers working to reduce suicide behavior among Ghanaian adolescents., (© 2024 American Association of Suicidology.)
Published: 2024
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42. Number of Prescription Medications and Overall Survival in Metastatic Castrate-Resistant Prostate Cancer.

Author: Pickett CR, Eaton DB, Karunanandaa K, Cybulla E, Heiden BT, Chang SH, Yan Y, Subramanian MP, Puri V, and Schoen MW
Abstract: Background: Assessment of comorbid diseases is essential to clinical research and may risk-stratify patients for mortality independent of established methods such as the Charlson Comorbidity Index (CCI). Methods: In a retrospective study of U.S. Veterans, we examined the association between the number of medications, 1-year mortality, and overall survival in Veterans being treated for metastatic castration-resistant prostate cancer (mCRPC) between 2011 and 2017. Results: Among 8855 Veterans, a median of 11 medications and 6 medication classes were filled in the year prior to initial treatment of mCRPC with abiraterone or enzalutamide. The median patient age was 74 years, 25.7% of patients were Black, and the median CCI was 3. Despite being associated with fewer medications, increasing age was associated with an increased CCI. After adjusting for patient, tumor, and treatment factors, both the number of medications and the number of medication classes were associated with increased 1-year mortality with adjusted OR (95% CI) of 1.03 (1.03, 1.04) and 1.08 (1.06, 1.11), respectively. Medications within Anatomic Therapeutic Class (ATC) N (nervous system) and ATC G (genitourinary and sex hormones) were associated with decreased OS, HR 1.18 (1.11, 1.25) and HR 1.15 (1.10, 1.20), respectively. Medications within ATC C (cardiovascular) were associated with increased OS, HR 0.91 (0.86, 0.97). Within a subgroup of patients with comparable age and CCI, the increased number of medications was associated with the increased risk of death. Conclusions: The number and type of medications were independently associated with survival in patients undergoing treatment for mCRPC. With new therapies for treatment of advanced prostate cancer, patients are living longer, which increases the need for better understanding of the impact of comorbid diseases. Simple methods to assess disease burden and prognosticate survival have the potential to guide treatment decisions and improve the quality of life in this patient population., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Carley R. Pickett et al.)
Published: 2024
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43. Perceptions of a faculty-trainee group mentorship program, the mentorship families program, in a residency training program: results from a cross-sectional survey.

Author: Amonoo HL, Funk MC, Guo M, Meyer F, Wolfe ED, Palamara K, Dzara K, Joffe H, Boland R, and Silbersweig D
Subjects: Cross-Sectional Studies, Humans, Mentoring, Program Evaluation, Female, Surveys and Questionnaires, Male, Adult, Psychiatry education, Internship and Residency, Faculty, Medical, Mentors
Abstract: Background: In residency programs, the availability of faculty mentors for traditional dyadic mentorship relationships may be limited. Few frameworks exist for mentorship programs with a combined faculty and peer mentorship approach. The authors developed the Mentorship Families Program (MFP), a faculty-resident group mentorship program within a psychiatry residency program to meet the need for mentorship for a large cohort of residents. A cross-sectional survey was used to evaluate the impact of the MFP after its first implementation year., Methods: Eleven mentorship families were created with 11 faculty members and 45 residents; each mentorship family consisted of one faculty member and 4-5 residents. A cross-sectional survey characterized the one-year perceived impact (2021-2022) of the MFP on resident and faculty mentoring experiences, with questions about the content, frequency, and quality of the MFP meetings and the strengths and areas of improvement for the MFP. Descriptive statistics were used to summarize quantitative feedback; directed content analysis was performed on open-ended feedback., Results: Twenty-seven residents (60%) and 8 faculty members (73%) responded to the survey. 70% of mentorship families met at least once. The MFP helped foster resident-faculty connections and provided an environment to gain career advice. However, residents and faculty reported challenges with scheduling meetings and a lack of meeting structure as barriers to effective engagement with the MFP. Most residents recommended that other training programs implement a program like the MFP as it offered multidimensional opportunities for connections between residents and faculty., Conclusions: A faculty-resident group mentorship program like the MFP can be implemented in residency training programs when traditional one-to-one faculty mentorship is often limited., Competing Interests: Declarations. Ethics approval and consent to participate: The Mass General Brigham Institutional Review Board deemed the study exempt from IRB review on 06/01/22, reference number 2022P001190. All study protocols were approved by the Mass General Brigham Institutional Review Board. Participants gave informed consent via completion of the voluntary anonymous survey. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)
Published: 2024
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44. Unusual Presentation of Extrapulmonary Tuberculosis as Laryngeal Mass in an Atypical Patient.

Author: Agarwal RD, Marino MD, Whalen MJ, and Walker RJ
Abstract: Spread of Mycobacterium tuberculosis (MTB) to the larynx is exceedingly rare and can be obscured by more common conditions such as laryngeal cancer or oropharyngeal candidiasis, complicating an accurate diagnosis. Risk factors for chronic laryngeal disease, such as smoking and toxin exposure, place TB infection comparatively lower for consideration on a physician's differential. However, identifying these lesions is crucial from a medical and public health perspective to prevent community spread. We report the case of a 60-year-old male who presented with dysphonia, pharyngitis, aphasia, and significant unintentional weight loss. X-rays demonstrated focal opacities in the upper lung lobes. Laryngoscope biopsy revealed caseating granulomas and a positive culture for MTB. Laryngeal TB presents as a suspicious throat mass with nonspecific symptoms and should be thoroughly investigated by clinicians., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Rohan Dipesh Agarwal et al.)
Published: 2024
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45. Live Attenuated Vaccine Administration in Children Treated With Methotrexate or Dupilumab.

Author: Hughes JR, Mehrmal S, Habib S, Williams HL, and Siegfried EC
Abstract: Background and Objectives: A wholesale recommendation against use of live virus vaccines in patients treated with any medication classified as an immunosuppressant has been based on global theoretical concerns rather than clinical outcomes for specific drugs., Methods: A retrospective search of electronic medical records identified patients seen by the Allergy and/or Dermatology services between 2017 and 2023 at a pediatric tertiary center who received a live attenuated vaccine during the 6 week interval prior to the first prescription for methotrexate or dupilumab until 6 weeks after the last prescription for either medication. Individual charts of identified patients were manually reviewed for evidence of adverse events., Results: The search identified 313 pediatric patients treated with dupilumab and/or methotrexate during the 7-year interval. Five of these patients received the combination measles, mumps, rubella, and varicella (MMRV) vaccine while on dupilumab and 4 while on methotrexate. Manual chart review was without evidence of adverse events for up to 6 months after immunization., Conclusions: This retrospective search identified a small number of pediatric patients immunized with the live attenuated MMRV vaccine during concomitant treatment with dupilumab or methotrexate. No associated adverse events were identified. Further investigation is needed to establish the safety and efficacy of live vaccines in patients treated with these immunomodulating agents., (© 2024 Wiley Periodicals LLC.)
Published: 2024
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46. Relationship Between Sleep Disturbances and Chronic Pain: A Narrative Review.

Author: Jain SV, Panjeton GD, and Martins YC
Abstract: Sleep disturbances and chronic pain are prevalent and interrelated conditions that have significant impact on individuals' quality of life. Understanding the intricate dynamics between sleep and pain is crucial for developing effective treatments that enhance the well-being of affected individuals and reduce the economic burden of these debilitating conditions. This narrative review examines the complex relationship between sleep disturbances and chronic pain. We describe the prevalence and types of sleep disturbances and sleep disorders in chronic pain patients. Posteriorly, we critically review the clinical and experimental evidence, investigating the relationship between sleep disturbances and chronic pain, aiming to clarify the impact of chronic pain on sleep and, conversely, the impact of sleep disturbances on pain perception. In conclusion, the literature largely agrees on the existence of a bidirectional relationship between chronic pain and sleep disturbances, though the strength of each direction in this association remains uncertain. Current evidence suggests that sleep impairment more strongly predicts pain than pain does sleep impairment. Additionally, addressing sleep disturbances in chronic pain patients is crucial, as poor sleep has been linked to higher levels of disability, depression, and pain-related catastrophizing.
Published: 2024
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47. Adipose tissue biology and effect of weight loss in women with lipedema.

Author: Cifarelli V, Smith GI, Gonzalez-Nieves S, Samovski D, Palacios HH, Yoshino J, Stein RI, Fuchs A, Wright TF, and Klein S
Abstract: Lipedema is a lipodystrophic disease that is typically characterized by a marked increase in lower-body subcutaneous adipose tissue that is purported to have increased inflammation and fibrosis, impaired microvascular/lymphatic circulation and to be resistant to reduction by weight loss therapy. However, these outcomes have not been adequately studied. We evaluated body composition, insulin sensitivity, metabolic health and adipose tissue biology in women with obesity and lipedema (Obese-LIP) before and after moderate (~9%) diet-induced weight loss. At baseline, people with Obese-LIP had ~23% greater leg fat mass, ~11% lower android-to-gynoid ratio and ~48% greater insulin sensitivity (all P<0.05) than women matched on age, BMI and whole-body adiposity. In Obese-LIP, macrophage content and expression of genes involved in inflammation and fibrosis were greater, whereas lymph/angiogenesis-related genes were lower in thigh than abdominal subcutaneous adipose tissue. Weight loss improved insulin sensitivity and decreased total fat mass, with similar relative reductions in abdominal and leg fat masses, but without changes in markers of inflammation and fibrosis. These results demonstrate that affected adipose tissue in women with lipedema is characterized by increased inflammation and fibrogenesis, and alterations in lymphatic and vascular biology. Moderate diet-induced weight loss improves metabolic function and decreases lower-body adipose tissue mass., (© 2024 by the American Diabetes Association.)
Published: 2024
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48. Single-Nucleotide Polymorphisms in Thrombotic Thrombocytopenic Purpura: A Genetic Predisposition to Immune Thrombotic Thrombocytopenic Purpura.

Author: Konopnicki A, Rischall A, and Jana B
Abstract: There are two main classifications for thrombotic thrombocytopenic purpura (TTP): immune and hereditary. The majority of TTP cases are immune in nature and are due to inhibitor autoantibodies against ADAMTS13. Hereditary TTP is caused by biallelic pathogenic variants in the ADAMTS13 gene. Immune TTP is treated with therapeutic plasma exchange that both removes inhibitor autoantibodies and repletes deficient ADAMTS13. In hereditary TTP, the treatment is plasma infusion, as there are no inhibitor autoantibodies to remove. Our case report presents a 72-year-old male who experienced recurrent episodes of TTP and whose first episode was complicated by an occipital lobe stroke. Next-generation sequencing revealed three separate homozygous single-nucleotide polymorphisms (SNPs) in exon 1, exon 12, and exon 16 of the ADAMTS13 gene. Inhibitor autoantibody testing was negative in recurrent episodes, and treatment with plasma infusions for hereditary TTP led to relapses. The objective of our case report is to explore the combined effects of these SNPs on ADAMTS13 activity and antigen levels and question if these genetic variations can lower the threshold for an immune TTP episode. Future research is required to determine if lower-than-normal baseline ADAMTS13 activity levels can predispose a patient to TTP and the long-term complications associated with it., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Konopnicki et al.)
Published: 2024
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49. Relationships Between Markers of Iron Status and Hematological Parameters in Patients With Sickle Cell Disease.

Author: Parrow NL, Doherty JM, Conrey A, Thein SL, and Fleming RE
Abstract: Based on the relationship between the intracellular concentration of sickle hemoglobin S (HbS) and the delay that occurs prior to the onset of sickling following deoxygenation, targeting the intracellular HbS concentration is a recognized therapeutic approach for sickle cell disease (SCD). We and others have shown that restricting iron by dietary or pharmacologic means improves hematologic parameters, inflammation, and organ damage in mouse models of SCD. Clinical evidence corroborating these findings is confined to case reports and small case series studies, none of which account for treatment or α -thalassemia. We hypothesize that increased transferrin saturation is associated with increased mean cellular hemoglobin concentration (MCHC) which in turn is associated with decreased red cell counts and worsening anemia. To investigate this hypothesis, we examined the relationships between transferrin saturation and MCHC with each of the parameters that define MCHC in sickle patients (HbSS without α -thalassemia) and healthy volunteers (HVs). Results indicate that transferrin saturation and MCHC are positively correlated with each other in sickle patients and HV. In patients with SCD, MCHC and transferrin saturation are negatively correlated with RBC count and are not correlated with hemoglobin, whereas each is positively associated with HV. Transferrin saturation and MCHC are each positively correlated with the hemolysis marker, lactate dehydrogenase. These observations support a model where increased transferrin saturation contributes to higher intracellular HbS concentrations with subsequent increases in sickling and hemolysis in sickle patients, suggesting that pharmacologic approaches to decrease serum iron may provide a therapeutic approach for patients with SCD. Trial Registration: This study was registered with ClinicalTrials.gov identifiers: NCT00011648, NCT00081523, and NCT04817670., Competing Interests: R.E.F. is a member of the Scientific Advisory Board of Silence Therapeutics and receives research funding from Ultragenyx, N.L.P. and R.E.F. serve as consultants for Protagonist Therapeutics., (Copyright © 2024 Nermi L. Parrow et al.)
Published: 2024
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50. A Healthcare Crisis: The Burden of Operating Room Travelers Contributes to Surgeon Burnout.

Author: Patel SS, Lu N, Gupta R, and Mailey BA
Abstract: Competing Interests: The authors have no financial interest to declare in relation to the content of this article.
Published: 2024
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